Novel proteins and nucleic acids encoding same

Abstract
The present invention provides novel isolated polynucleotides and small molecule target polypeptides encoded by the polynucleotides. Antibodies that immunospecifically bind to a novel small molecule target polypeptide or any derivative, variant, mutant or fragment of that polypeptide, polynucleotide or antibody are disclosed, as are methods in which the small molecule target polypeptide, polynucleotide and antibody are utilized in the detection and treatment of a broad range of pathological states. More specifically, the present invention discloses methods of using recombinantly expressed and/or endogenously expressed proteins in various screening procedures for the purpose of identifying therapeutic antibodies and therapeutic small molecules associated with diseases.
Description


FIELD OF THE INVENTION

[0002] The present invention relates to novel polypeptides that are targets of small molecule drugs and that have properties related to stimulation of biochemical or physiological responses in a cell, a tissue, an organ or an organism. More particularly, the novel polypeptides are gene products of novel genes, or are specified biologically active fragments or derivatives thereof. Methods of use encompass diagnostic and prognostic assay procedures as well as methods of treating diverse pathological conditions. The present invention discloses novel associations of proteins and polypeptides and the nucleic acids that encode them with various diseases or pathologies. The proteins and related proteins that are similar to them, are encoded by a cDNA and/or by genomic DNA. The proteins, polypeptides and their cognate nucleic acids were identified by Curagen Corporation in certain cases. The XYZase-encoded protein and any variants, thereof, are suitable as diagnostic markers, targets for an antibody therapeutic and targets for small molecule drugs. As such the current invention embodies the use of recombinantly expressed and/or endogenously expressed protein in various screens to identify such therapeutic antibodies and/or therapeutic small molecules.



BACKGROUND

[0003] Eukaryotic cells are characterized by biochemical and physiological processes which under normal conditions are exquisitely balanced to achieve the preservation and propagation of the cells. When such cells are components of multicellular organisms such as vertebrates, or more particularly organisms such as mammals, the regulation of the biochemical and physiological processes involves intricate signaling pathways. Frequently, such signaling pathways are constituted of extracellular signaling proteins, cellular receptors that bind the signaling proteins and signal transducing components located within the cells.


[0004] Signaling proteins may be classified as endocrine effectors, paracrine effectors or autocrine effectors. Endocrine effectors are signaling molecules secreted by a given organ into the circulatory system, which are then transported to a distant target organ or tissue. The target cells include the receptors for the endocrine effector, and when the endocrine effector binds, a signaling cascade is induced. Paracrine effectors involve secreting cells and receptor cells in close proximity to each other, for example two different classes of cells in the same tissue or organ. One class of cells secretes the paracrine effector, which then reaches the second class of cells, for example by diffusion through the extracellular fluid. The second class of cells contains the receptors for the paracrine effector; binding of the effector results in induction of the signaling cascade that elicits the corresponding biochemical or physiological effect. Autocrine effectors are highly analogous to paracrine effectors, except that the same cell type that secretes the autocrine effector also contains the receptor. Thus the autocrine effector binds to receptors on the same cell, or on identical neighboring cells. The binding process then elicits the characteristic biochemical or physiological effect.


[0005] Signaling processes may elicit a variety of effects on cells and tissues including by way of nonlimiting example induction of cell or tissue proliferation, suppression of growth or proliferation, induction of differentiation or maturation of a cell or tissue, and suppression of differentiation or maturation of a cell or tissue.


[0006] Many pathological conditions involve dysregulation of expression of important effector proteins. In certain classes of pathologies the dysregulation is manifested as diminished or suppressed level of synthesis and secretion protein effectors. In a clinical setting a subject may be suspected of suffering from a condition brought on by diminished or suppressed levels of a protein effector of interest. Therefore there is a need to be able to assay for the level of the protein effector of interest in a biological sample from such a subject, and to compare the level with that characteristic of a nonpathological condition. There further is a need to provide the protein effector as a product of manufacture. Administration of the effector to a subject in need thereof is useful in treatment of the pathological condition, or the protein effector deficiency or suppression may be favorably acted upon by the administration of another small molecule drug product. Accordingly, there is a need for a method of treatment of a pathological condition brought on by a diminished or suppressed levels of the protein effector of interest.


[0007] Small molecule targets have been implicated in various disease states or pathologies. These targets may be proteins, and particularly enzymatic proteins, which are acted upon by small molecule drugs for the purpose of altering target function and achieving a desired result. Cellular, animal and clinical studies can be performed to elucidate the genetic contribution to the etiology and pathogenesis of conditions in which small molecule targets are implicated in a variety of physiologic, pharmacologic or native states. These studies utilize the core technologies at CuraGen Corporation to look at differential gene expression, protein-protein interactions, large-scale sequencing of expressed genes and the association of genetic variations such as, but not limited to, single nucleotide polymorphisms (SNPs) or splice variants in and between biological samples from experimental and control groups. The goal of such studies is to identify potential avenues for therapeutic intervention in order to prevent, treat the consequences or cure the conditions.


[0008] In order to treat diseases, pathologies and other abnormal states or conditions in which a mammalian organism has been diagnosed as being, or as being at risk for becoming, other than in a normal state or condition, it is important to identify new therapeutic agents. Such a procedure includes at least the steps of identifying a target component within an affected tissue or organ, and identifying a candidate therapeutic agent that modulates the functional attributes of the target. The target component may be any biological macromolecule implicated in the disease or pathology. Commonly the target is a polypeptide or protein with specific functional attributes. Other classes of macromolecule may be a nucleic acid, a polysaccharide, a lipid such as a complex lipid or a glycolipid; in addition a target may be a sub-cellular structure or extra-cellular structure that is comprised of more than one of these classes of macromolecule. Once such a target has been identified, it may be employed in a screening assay in order to identify favorable candidate therapeutic agents from among a large population of substances or compounds.


[0009] In many cases the objective of such screening assays is to identify small molecule candidates; this is commonly approached by the use of combinatorial methodologies to develop the population of substances to be tested. The implementation of high throughput screening methodologies is advantageous when working with large, combinatorial libraries of compounds.


[0010] It is an objective of this invention to provide at least one target biopolymer that is intended to serve as the macromolecular component in a screening assay for identifying candidate pharmaceutical agents.


[0011] It is another objective of the present invention to provide screening assays that positively identify candidate pharmaceutical agents from among a combinatorial library of low molecular weight substances or compounds.


[0012] It is still a further objective of this invention to employ the candidate pharmaceutical agents in any of a variety of in vitro, ex vivo and in vivo assays in order to identify pharmaceutical agents with advantageous therapeutic applications in the treatment of a disease, pathology, or abnormal state or condition in a mammal.



SUMMARY OF THE INVENTION

[0013] The invention is based in part upon the discovery of nucleic acid sequences encoding novel polypeptides. These nucleic acids and polypeptides, as well as derivatives, homologs, analogs and fragments thereof, will hereinafter be collectively designated as “NOVX” nucleic acid, which represents the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178, or polypeptide sequences, which represents the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 178.


[0014] In one aspect, the invention provides an isolated polypeptide comprising a mature form of a NOVX amino acid. One example is a variant of a mature form of a NOVX amino acid sequence, wherein any amino acid in the mature form is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed. The amino acid can be, for example, a NOVX amino acid sequence or a variant of a NOVX amino acid sequence, wherein any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed. The invention also includes fragments of any of these. In another aspect, the invention also includes an isolated nucleic acid that encodes a NOVX polypeptide, or a fragment, homolog, analog or derivative thereof.


[0015] Also included in the invention is a NOVX polypeptide that is a naturally occurring allelic variant of a NOVX sequence. In one embodiment, the allelic variant includes an amino acid sequence that is the translation of a nucleic acid sequence differing by a single nucleotide from a NOVX nucleic acid sequence. In another embodiment, the NOVX polypeptide is a variant polypeptide described therein, wherein any amino acid specified in the chosen sequence is changed to provide a conservative substitution. In one embodiment, the invention discloses a method for determining the presence or amount of the NOVX polypeptide in a sample. The method involves the steps of: providing a sample; introducing the sample to an antibody that binds immunospecifically to the polypeptide; and determining the presence or amount of antibody bound to the NOVX polypeptide, thereby determining the presence or amount of the NOVX polypeptide in the sample. In another embodiment, the invention provides a method for determining the presence of or predisposition to a disease associated with altered levels of a NOVX polypeptide in a mammalian subject. This method involves the steps of: measuring the level of expression of the polypeptide in a sample from the first mammalian subject; and comparing the amount of the polypeptide in the sample of the first step to the amount of the polypeptide present in a control sample from a second mammalian subject known not to have, or not to be predisposed to, the disease, wherein an alteration in the expression level of the polypeptide in the first subject as compared to the control sample indicates the presence of or predisposition to the disease.


[0016] In a further embodiment, the invention includes a method of identifying an agent that binds to a NOVX polypeptide. This method involves the steps of: introducing the polypeptide to the agent; and determining whether the agent binds to the polypeptide. In various embodiments, the agent is a cellular receptor or a downstream effector.


[0017] In another aspect, the invention provides a method for identifying a potential therapeutic agent for use in treatment of a pathology, wherein the pathology is related to aberrant expression or aberrant physiological interactions of a NOVX polypeptide. The method involves the steps of: providing a cell expressing the NOVX polypeptide and having a property or function ascribable to the polypeptide; contacting the cell with a composition comprising a candidate substance; and determining whether the substance alters the property or function ascribable to the polypeptide; whereby, if an alteration observed in the presence of the substance is not observed when the cell is contacted with a composition devoid of the substance, the substance is identified as a potential therapeutic agent. In another aspect, the invention describes a method for screening for a modulator of activity or of latency or predisposition to a pathology associated with the NOVX polypeptide. This method involves the following steps: administering a test compound to a test animal at increased risk for a pathology associated with the NOVX polypeptide, wherein the test animal recombinantly expresses the NOVX polypeptide. This method involves the steps of measuring the activity of the NOVX polypeptide in the test animal after administering the compound of step; and comparing the activity of the protein in the test animal with the activity of the NOVX polypeptide in a control animal not administered the polypeptide, wherein a change in the activity of the NOVX polypeptide in the test animal relative to the control animal indicates the test compound is a modulator of latency of, or predisposition to, a pathology associated with the NOVX polypeptide. In one embodiment, the test animal is a recombinant test animal that expresses a test protein transgene or expresses the transgene under the control of a promoter at an increased level relative to a wild-type test animal, and wherein the promoter is not the native gene promoter of the transgene. In another aspect, the invention includes a method for modulating the activity of the NOVX polypeptide, the method comprising introducing a cell sample expressing the NOVX polypeptide with a compound that binds to the polypeptide in an amount sufficient to modulate the activity of the polypeptide.


[0018] The invention also includes an isolated nucleic acid that encodes a NOVX polypeptide, or a fragment, homolog, analog or derivative thereof. In a preferred embodiment, the nucleic acid molecule comprises the nucleotide sequence of a naturally occurring allelic nucleic acid variant. In another embodiment, the nucleic acid encodes a variant polypeptide, wherein the variant polypeptide has the polypeptide sequence of a naturally occurring polypeptide variant. In another embodiment, the nucleic acid molecule differs by a single nucleotide from a NOVX nucleic acid sequence. In one embodiment, the NOVX nucleic acid molecule hybridizes under stringent conditions to the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178, or a complement of the nucleotide sequence. In another aspect, the invention provides a vector or a cell expressing a NOVX nucleotide sequence.


[0019] In one embodiment, the invention discloses a method for modulating the activity of a NOVX polypeptide. The method includes the steps of: introducing a cell sample expressing the NOVX polypeptide with a compound that binds to the polypeptide in an amount sufficient to modulate the activity of the polypeptide. In another embodiment, the invention includes an isolated NOVX nucleic acid molecule comprising a nucleic acid sequence encoding a polypeptide comprising a NOVX amino acid sequence or a variant of a mature form of the NOVX amino acid sequence, wherein any amino acid in the mature form of the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed. In another embodiment, the invention includes an amino acid sequence that is a variant of the NOVX amino acid sequence, in which any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed.


[0020] In one embodiment, the invention discloses a NOVX nucleic acid fragment encoding at least a portion of a NOVX polypeptide or any variant of the polypeptide, wherein any amino acid of the chosen sequence is changed to a different amino acid, provided that no more than 10% of the amino acid residues in the sequence are so changed. In another embodiment, the invention includes the complement of any of the NOVX nucleic acid molecules or a naturally occurring allelic nucleic acid variant. In another embodiment, the invention discloses a NOVX nucleic acid molecule that encodes a variant polypeptide, wherein the variant polypeptide has the polypeptide sequence of a naturally occurring polypeptide variant. In another embodiment, the invention discloses a NOVX nucleic acid, wherein the nucleic acid molecule differs by a single nucleotide from a NOVX nucleic acid sequence.


[0021] In another aspect, the invention includes a NOVX nucleic acid, wherein one or more nucleotides in the NOVX nucleotide sequence is changed to a different nucleotide provided that no more than 15% of the nucleotides are so changed. In one embodiment, the invention discloses a nucleic acid fragment of the NOVX nucleotide sequence and a nucleic acid fragment wherein one or more nucleotides in the NOVX nucleotide sequence is changed from that selected from the group consisting of the chosen sequence to a different nucleotide provided that no more than 15% of the nucleotides are so changed. In another embodiment, the invention includes a nucleic acid molecule wherein the nucleic acid molecule hybridizes under stringent conditions to a NOVX nucleotide sequence or a complement of the NOVX nucleotide sequence. In one embodiment, the invention includes a nucleic acid molecule, wherein the sequence is changed such that no more than 15% of the nucleotides in the coding sequence differ from the NOVX nucleotide sequence or a fragment thereof.


[0022] In a further aspect, the invention includes a method for determining the presence or amount of the NOVX nucleic acid in a sample. The method involves the steps of: providing the sample; introducing the sample to a probe that binds to the nucleic acid molecule; and determining the presence or amount of the probe bound to the NOVX nucleic acid molecule, thereby determining the presence or amount of the NOVX nucleic acid molecule in the sample. In one embodiment, the presence or amount of the nucleic acid molecule is used as a marker for cell or tissue type.


[0023] In another aspect, the invention discloses a method for determining the presence of or predisposition to a disease associated with altered levels of the NOVX nucleic acid molecule of in a first mammalian subject. The method involves the steps of: measuring the amount of NOVX nucleic acid in a sample from the first mammalian subject; and comparing the amount of the nucleic acid in the sample of step (a) to the amount of NOVX nucleic acid present in a control sample from a second mammalian subject known not to have or not be predisposed to, the disease; wherein an alteration in the level of the nucleic acid in the first subject as compared to the control sample indicates the presence of or predisposition to the disease.


[0024] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In the case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.


[0025] Other features and advantages of the invention will be apparent from the following detailed description and claims.



DETAILED DESCRIPTION OF THE INVENTION

[0026] The present invention provides novel nucleotides and polypeptides encoded thereby. Included in the invention are the novel nucleic acid sequences, their encoded polypeptides, antibodies, and other related compounds. The sequences are collectively referred to herein as “NOVX nucleic acids” or “NOVX polynucleotides” and the corresponding encoded polypeptides are referred to as “NOVX polypeptides” or “NOVX proteins.” Unless indicated otherwise, “NOVX” is meant to refer to any of the novel sequences disclosed herein. Table 1 provides a summary of the NOVX nucleic acids and their encoded polypeptides.
1TABLE 1Sequences and Corresponding SEQ ID NumbersNucleicAminoAcidAcidSEQSEQNOVXInternalIDIDNo.Acc. No.NO.NO.Homology 1aCG58522-0112human plateletactivating factoracetylhydrolase 2aCG58520-0134GABA(A) receptor 2bCG58520-0256GABA(A) receptor 2cCG58520-0378GABA(A) receptor 3aCG58518-01910GABA(A) receptor 4aCG58516-011112Beta transducin 5aCG58473-011314Protein kinase 6aCG58470-011516UDP-N-acetylhexosaminepyrophosphorylase 7aCG58593-011718ubiquitin 52 like 8aCG57871-011920tousled like kinase like 9aCG58590-012122guanylate kinase like 9bCG58590-022324guanylate kinase like 10aCG58572-012526glucosamine phosphateN acetyltransferase like 10bCG58572-022728glucosamine phosphateN acetyltransferase like 11aCG58564-012930Protein tyrosinephosphatase like 11bCG58564-023132Protein tyrosinephosphatase like 11cCG58564-033334Dual-Specificityphosphatase like 11dCG58564-043536Dual-Specificityphosphatase like 12aCG57819-013738RPGR interactingprotein 1 like 13aCG57789-013940RAS like proteinRRP22 like 13bCG57789-024142RAS like proteinRRP22 like 14aCG57758-014344sodium/lithiumdependentdicarboxylatetransporter like 14bCG57758-024546sodium/lithiumdependentdicarboxylatetransporter like 14cCG57758-034748sodium/lithiumdependentdicarboxylatetransporter like 14dCG57758-044950sodium/lithiumdependentdicarboxylatetransporter like 14eCG57758-055152sodium/lithiumdependentdicarboxylatetransporter like 15aCG57732-015354Ca 2 + calmodulindependent proteinkinase IV kinase like 15bCG57732-025556Ca 2 + calmodulindependent proteinkinase IV kinase like 15cCG57732-035758Ca 2 + calmodulindependent proteinkinase IV kinase like 16aCG57709-015960TCE2 like 17aCG57700-016162hydoxyacylglutathionehydrolase like 17bCG57700-026364hydoxyacylglutathionehydrolase like 17cCG57700-036566hydoxyacylglutathionehydrolase like 17dCG57700-046768hydoxyacylglutathionehydrolase like 18aCG58553-016970vasopressin receptorlike 19aCG58626-017172phosphatidic acidpreferringphospholipase A1 like 20aCG57597-017374hypothetical proteinlike 21aCG57804-017576Talin like 22aCG57551-017778NAC-1 like 23aCG57411-017980Kelch like 24aCG57399-018182phospholipaseADRAB-B precursorlike 24bCG57399-028384phospholipaseADRAB-B precursorlike 24cCG57399-038586phospholipaseADRAB-B precursorlike 25aCG59311-018788acyl-coenzyme Athioester hydrolase 25bCG59311-028990peroxisomal acyl-coenzyme A thioeseterhydrolase like 25cCG59311-039192peroxisomal acyl-coenzyme A thioeseterhydrolase like 26aCG59309-019394acyl-coenzyme Athioester hydrolase 27aCG57364-019596CG6896 28aCG59348-019798cytoplasmic protein(patent calls this CyclinL-like) 29aCG59245-0199100glucose 6-phosphatase 29bCG59245-02101102glucose 6-phosphatase 30aCG59241-01103104Amiloride-sensitivesodium channel 31aCG58602-01105106FAD binding domaincontaining protein 32aCG58468-01107108Serum Amyloid Protein 33aCG58183-01109110N-Methyl-D-Aspartatereceptor 34aCG59315-01111112Connexin 35aCG59203-01113114lysozyme C 35bCG59203-02115116lysozyme C 36aCG58662-01117118cytoplasmic protein 36bCG58662-02119120cytoplasmic protein 37aCG58584-01121122405 ribosomal proteinS29 like 38aCG58538-01123124Histone deacetylasecomplex protein 66 like 39aCG59371-01125126expressed cytoplasmicprotein like 40aCG59346-01127128cortactin bindingprotein 1 like 41aCG57814-01129130Basic I 19 like homosapiens 41bCG57814-02131132Basic I 19 like homosapiens 42aCG59327-01133134Monocarboxylatetransporter 1 like 43aCG59494-01135136myelin P2 like 44aCG59432-0l137138chloride channel like 44bCG59432-02139140chloride channel like 45aCG59394-01141142GPCR like 46aCG59383-01143144D6MM5E PROTEINlike 46bCG59383-02145146D6MM5E PROTEINlike 47aCG58526-01147148scramblase like 48aCG57851-01149150sulfotransferase like 49aCG59377-01151152epsin like 50aCG59258-01153154transcriptional activatorlike 51aCG59492-01155156Myosin Head (MotorDomain) like 52aCG59564-01157158Sorting nexin 6 like 53aCG59553-01159160Secretory protein SECSlike 54aCG59545-01161162Placental protein 13like 55aCG59435-01163164Nedd-1 like 55bCG59435-02165166Nedd-1 like 56aCG59439-01167168Xenobiotic/medium-chain fatty acid: CoAligase form XL-III like 56bCG59439-02169170Xenobiotic/medium-chain fatty acid: CoAligase form XL-III like 57aCG59354-01171172phosducin like 57bCG59354-02173174phosducin like 57cCG59354-03175176phosducin like 58aCG59319-01177178phosducin like 58bCG59319-02179180phosducin like 59aCG59576-01181182GPCR like 60aCG59557-01183184GPCR like 61aCG59555-01185186GPCR like 62aCG59551-01187188GPCR like 63aCG59540-01189190GPCR like 64aCG59280-01191192GPCR like 64bCG59280-02193194GPCR like 65aCG59568-01195196GPCR like 66aCG59224-01197198GPCR like 67aCG59222-01199200GPCR like 68aCG59220-01201202GPCR like 69aCG59218-0l203204GPCR like 70aCG59216-01205206GPCR like 71aCG59214-01207208GPCR like 72aCG59211-01209210GPCR like 73aCG59276-01211212Dihydroorotatedehydrogenase like 74aCG59268-01213214monooxygenase like 75aCG59549-01215216H326 like (cytoplasmicprotein with WD repeatdomain) 76aCG59641-01217218Acetyl-CoACarboxylase 2 like 77aCG59630-01219220Midnolin like 78aCG59561-01221222ACYL COENZYME ATHIOESTERHYDROLASE like 79aCG59452-01223224CELLPROLIFERATIONRELATED PROTEINCAP like 80aCG59572-01225226Pseudouridine Synthase3 like 80bCG59572-02227228Pseudouridine Synthase3 like 81aCG59522-01229230Myosin like 82aCG59520-01231232Farnesyl-pyrophosphatesynthetase like 83aCG59758-01233234UBIQUITIN like 83bCG59758-02235236UBIQUITIN like 84aCG59586-01237238glucokinase like 85aCG59704-01239240serine/threonine kinaselike 86aCG59628-01241242Short-chaindehydrogenase like 87aCG59516-01243244Calponin like 87bCG59516-02245246Calponin like 88aCG59671-02247248acyl-coenzyme Athioester hydrolase 89aCG56870-01249250NDRG3 like 89bCG56870-02251252NDRG3 like 89cCG56870-03253254NDRG3 like 89dCG56870-04255256NDRG3 like 89eCG56870-05257258NDRG3 like 90aCG59764-01259260Ferritin like 91aCG59710-01261262P14 like 92aCG59754-02263264Downs syndrome celladhesion molecule like 92bCG59754-01265266Downs syndrome celladhesion molecule like 93aCG59800-01267268HEPARAN SULFATED-GLUCOSAMINYL3-O-SULFOTRANSFERASE-3Blike 94aCG59761-01269270AXIN I (AXISINHIBITIONPROTEIN I) (HAXIN)like 95aCG59756-01271272JUNCTOPHILINTYPE 2 like 96aCG59708-01273274Ubiquitin carboxyl-terminal hydrolase 21like 96bCG59708-02275276Ubiquitin carboxyl-terminal hydrolase 21like 96cCG59708-03277278Ubiquitin carboxyl-terminal hydrolase 21like 97aCG59559-01279280BA12M19.1.3 like 98aCG59669-01281282carbonyl reductase(called NADPH-dependent carbonylreductase-like inpatent) 99aCG58624-01283284metal transporter100aCG59679-01285286carbonyl reductase101aCG59644-01287288CG12091 (putativeprotein phosphatase)102aCG59662-01289290Cyclophilin103aCG59773-01291292Myomegalin103bCG59773-02293294Myomegalin103cCG59773-03295296Myomegalin104aCG57460-01297298PEPTIDYL-PROLYLCIS-TRANSISOMERASE like105aCG57464-01299300N-ACETYLTRANSFERASE like106aCG57466-01301302Acetylglucosaminyl-transferase like107aCG57468-01303304ABC transporter likehomo sapiens108aCG59609-01305306PEPTIDYL-PROLYLCIS-TRANSISOMERASE A like109aCG59613-01307308Proliferating cellnuclear antigen like110aCG59619-01309310CYTOPLASMICACTIN 2 like111aCG59621-01311312SELENOPHOSPHATESYNTHETASE like112aCG59625-01313314glucose transporter like113aCG59887-0l315316Amino Acid/MetabolitePermease like113bCG59887-02317318Amino Acid/MetabolitePermease like114aCG59861-01319320RIBULOSE-5-PHOSPHATEEPIMERASE like114bCG59861-02321322RIBULOSE-5-PHOSPHATEEPIMERASE like115aCG59857-01323324Rhotekin like homosapiens116aCG59855-0l325326ATP SYNTHASESUBUNIT C lik116bCG59855-02327328ATP SYNTHASESUBUNIT C like117aCG59807-01329330Zinc finger like118aCG59805-01331332Zinc finger like119aCG59928-01333334Universal Stress (USP)Domain ContainingProtein like120aCG59947-01335336VOLTAGE-GATEDPOTASSIUMCHANNEL PROTEINKV3.3 (KSHIIID) like121aCG59938-0l337338arylsulfatase like homosapiens122aCG59746-01339340ubiguitin-specificprocessing proteaselike homo sapiens123aCG88613-01341342INOSITOL 1,4,5-TRISPHOSPHATE 3-KINASEISOENZYME like124aCG59993-01343344synaptotagmin II like124bCG59993-02345346synaptotagmin 11 like125aCG59991-01347348ooplasm specificprotein like126aCG59987-01349350GTP-RHO bindingprotein 1 (rhophilin)like126bCG59987-02351352GTP-RHO bindingprotein 1 (rhophilin)like127aCG59971-01353354Leucine rich repeat(LRR) like127bCG59971-02355356Leucine rich repeat(LRR) like


[0027] Table 1 indicates homology of NOVX nucleic acids to known protein families. Thus, the nucleic acids and polypeptides, antibodies and related compounds according to the invention corresponding to a NOVX as identified in column 1 of Table 1 will be useful in therapeutic and diagnostic applications implicated in, for example, pathologies and disorders associated with the known protein families identified in column 5 of Table 1.


[0028] NOVX nucleic acids and their encoded polypeptides are useful in a variety of applications and contexts. The various NOVX nucleic acids and polypeptides according to the invention are useful as novel members of the protein families according to the presence of domains and sequence relatedness to previously described proteins. Additionally, NOVX nucleic acids and polypeptides can also be used to identify proteins that are members of the family to which the NOVX polypeptides belong.


[0029] Consistent with other known members of the family of proteins, identified in column 5 of Table 1, the NOVX polypeptides of the present invention show homology to, and contain domains that are characteristic of, other members of such protein families. Details of the sequence relatedness and domain analysis for each NOVX are presented in Example A.


[0030] The NOVX nucleic acids and polypeptides can also be used to screen for molecules, which inhibit or enhance NOVX activity or function. Specifically, the nucleic acids and polypeptides according to the invention may be used as targets for the identification of small molecules that modulate or inhibit diseases associated with the protein families listed in Table 1.


[0031] The NOVX nucleic acids and polypeptides are also useful for detecting specific cell types. Details of the expression analysis for each NOVX are presented in Example C. Accordingly, the NOVX nucleic acids, polypeptides, antibodies and related compounds according to the invention will have diagnostic and therapeutic applications in the detection of a variety of diseases with differential expression in normal vs. diseased tissues, e.g. a variety of cancers.


[0032] Additional utilities for NOVX nucleic acids and polypeptides according to the invention are disclosed herein.


[0033] The present invention is based on the identification of biological macromolecules differentially modulated in a pathologic state, disease, or an abnormal condition or state. Among the pathologies or diseases of present interest include metabolic diseases including those related to endocrinologic disorders, cancers, various tumors and neoplasias, inflammatory disorders, central nervous system disorders, and similar abnormal conditions or states. In very significant embodiments of the present invention, the biological macromolecules implicated in the pathologies and conditions are proteins and polypeptides, and in such cases the present invention is related as well to the nucleic acids that encode them. Methods that may be employed to identify relevant biological macromolecules include any procedures that detect differential expression of nucleic acids encoding proteins and polypeptides associated with the disorder, as well as procedures that detect the respective proteins and polypeptides themselves. Significant methods that have been employed by the present inventors, include GeneCalling® technology and SeqCalling TM technology, disclosed respectively, in U.S. Pat. No. 5,871,697, and in U. S. Ser. No. 09/417,386, filed Oct. 13, 1999, each of which is incorporated herein by reference in its entirety. GeneCalling® is also described in Shimkets, et al., “Gene expression analysis by transcript profiling coupled to a gene database query” Nature Biotechnology 17:198-803 (1999).


[0034] The invention provides polypeptides and nucleotides encoded thereby that have been identified as having novel associations with a disease or pathology, or an abnormal state or condition, in a mammal. The present invention further identifies a set of proteins and polypeptides, including naturally occurring polypeptides, precursor forms or proproteins, or mature forms of the polypeptides or proteins, which are implicated as targets for therapeutic agents in the treatment of various diseases, pathologies, abnormal states and conditions. A target may be employed in any of a variety of screening methodologies in order to identify candidate therapeutic agents which interact with the target and in so doing exert a desired or favorable effect. The candidate therapeutic agent is identified by screening a large collection of substances or compounds in an important embodiment of the invention. Such a collection may comprise a combinatorial library of substances or compounds in which, in at least one subset of substances or compounds, the individual members are related to each other by simple structural variations based on a particular canonical or basic chemical structure. The variations may include, by way of nonlimiting example, changes in length or identity of a basic framework of bonded atoms; changes in number, composition and disposition of ringed structures, bridge structures, alicyclic rings, and aromatic rings; and changes in pendent or substituents atoms or groups that are bonded at particular positions to the basic framework of bonded atoms or to the ringed structures, the bridge structures, the alicyclic structures, or the aromatic structures.


[0035] A polypeptide or protein described herein, and that serves as a target in the screening procedure, includes the product of a naturally occurring polypeptide or precursor form or proprotein. The naturally occurring polypeptide, precursor or proprotein includes, e.g., the full-length gene product, encoded by the corresponding gene. The naturally occurring polypeptide also includes the polypeptide, precursor or proprotein encoded by an open reading frame described herein. A “mature” form of a polypeptide or protein arises as a result of one or more naturally occurring processing steps as they may occur within the cell, including a host cell. The processing steps occur as the gene product arises, e.g., via cleavage of the amino-terminal methionine residue encoded by the initiation codon of an open reading frame, or the proteolytic cleavage of a signal peptide or leader sequence. Thus, a mature form arising from a precursor polypeptide or protein that has residues 1 to N, where residue 1 is the N-terminal methionine, would have residues 2 through N remaining. Alternatively, a mature form arising from a precursor polypeptide or protein having residues 1 to N, in which an amino-terminal signal sequence from residue 1 to residue M is cleaved, includes the residues from residue M+1 to residue N remaining. A “mature” form of a polypeptide or protein may also arise from non-proteolytic post-translational modification. Such non-proteolytic processes include, e.g., glycosylation, myristylation or phosphorylation. In general, a mature polypeptide or protein may result from the operation of only one of these processes, or the combination of any of them.


[0036] As used herein, “identical” residues correspond to those residues in a comparison between two sequences where the equivalent nucleotide base or amino acid residue in an alignment of two sequences is the same residue. Residues are alternatively described as “similar” or “positive” when the comparisons between two sequences in an alignment show that residues in an equivalent position in a comparison are either the same amino acid or a conserved amino acid as defined below.


[0037] As used herein, a “chemical composition” relates to a composition including at least one compound that is either synthesized or extracted from a natural source. A chemical compound may be the product of a defined synthetic procedure. Such a synthesized compound is understood herein to have defined properties in terms of molecular formula, molecular structure relating the association of bonded atoms to each other, physical properties such as chromatographic or spectroscopic characterizations, and the like. A compound extracted from a natural source is advantageously analyzed by chemical and physical methods in order to provide a representation of its defined properties, including its molecular formula, molecular structure relating the association of bonded atoms to each other, physical properties such as chromatographic or spectroscopic characterizations, and the like.


[0038] As used herein, a “candidate therapeutic agent” is a chemical compound that includes at least one substance shown to bind to a target biopolymer. In important embodiments of the invention, the target biopolymer is a protein or polypeptide, a nucleic acid, a polysaccharide or proteoglycan, or a lipid such as a complex lipid. The method of identifying compounds that bind to the target effectively eliminates compounds with little or no binding affinity, thereby increasing the potential that the identified chemical compound may have beneficial therapeutic applications. In cases where the “candidate therapeutic agent” is a mixture of more than one chemical compound, subsequent screening procedures may be carried out to identify the particular substance in the mixture that is the binding compound, and that is to be identified as a candidate therapeutic agent.


[0039] As used herein, a “pharmaceutical agent” is provided by screening a candidate therapeutic agent using models for a disease state or pathology in order to identify a candidate exerting a desired or beneficial therapeutic effect with relation to the disease or pathology. Such a candidate that successfully provides such an effect is termed a pharmaceutical agent herein. Nonlimiting examples of model systems that may be used in such screens include particular cell lines, cultured cells, tissue preparations, whole tissues, organ preparations, intact organs, and nonhuman mammals. Screens employing at least one system, and preferably more than one system, may be employed in order to identify a pharmaceutical agent. Any pharmaceutical agent so identified may be pursued in further investigation using human subjects.


[0040] NOVX Nucleic Acids and Polypeptides


[0041] NOVX Clones


[0042] NOVX nucleic acids and their encoded polypeptides are useful in a variety of applications and contexts. The various NOVX nucleic acids and polypeptides according to the invention are useful as novel members of the protein families according to the presence of domains and sequence relatedness to previously described proteins. Additionally, NOVX nucleic acids and polypeptides can also be used to identify proteins that are members of the family to which the NOVX polypeptides belong.


[0043] The NOVX genes and their corresponding encoded proteins are useful for preventing, treating or ameliorating medical conditions, e.g., by protein or gene therapy. Pathological conditions can be diagnosed by determining the amount of the new protein in a sample or by determining the presence of mutations in the new genes. Specific uses are described for each of the NOVX genes, based on the tissues in which they are most highly expressed. Uses include developing products for the diagnosis or treatment of a variety of diseases and disorders.


[0044] The NOVX nucleic acids and proteins of the invention are useful in potential diagnostic and therapeutic applications and as a research tool. These include serving as a specific or selective nucleic acid or protein diagnostic and/or prognostic marker, wherein the presence or amount of the nucleic acid or the protein are to be assessed, as well as potential therapeutic applications such as the following: (i) a protein therapeutic, (ii) a small molecule drug target, (iii) an antibody target (therapeutic, diagnostic, drug targeting/cytotoxic antibody), (iv) a nucleic acid useful in gene therapy (gene delivery/gene ablation), and (v) a composition promoting tissue regeneration in vitro and in vivo (vi) biological defense weapon.


[0045] In one specific embodiment, the invention includes an isolated polypeptide comprising an amino acid sequence selected from the group consisting of: (a) a mature form of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 178; (b) a variant of a mature form of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 178, wherein any amino acid in the mature form is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed; (c) an amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 178; (d) a variant of the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 178 wherein any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed; and (e) a fragment of any of (a) through (d).


[0046] In another specific embodiment, the invention includes an isolated nucleic acid molecule comprising a nucleic acid sequence encoding a polypeptide comprising an amino acid sequence selected from the group consisting of: (a) a mature form of the amino acid sequence given SEQ ID NO: 2n, wherein n is an integer between 1 and 178; (b) a variant of a mature form of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 178 wherein any amino acid in the mature form of the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed; (c) the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 178; (d) a variant of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 178, in which any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed; (e) a nucleic acid fragment encoding at least a portion of a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 178 or any variant of said polypeptide wherein any amino acid of the chosen sequence is changed to a different amino acid, provided that no more than 10% of the amino acid residues in the sequence are so changed; and (f) the complement of any of said nucleic acid molecules.


[0047] In yet another specific embodiment, the invention includes an isolated nucleic acid molecule, wherein said nucleic acid molecule comprises a nucleotide sequence selected from the group consisting of: (a) the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178; (b) a nucleotide sequence wherein one or more nucleotides in the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178 is changed from that selected from the group consisting of the chosen sequence to a different nucleotide provided that no more than 15% of the nucleotides are so changed; (c) a nucleic acid fragment of the sequence selected from the group consisting of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178; and (d) a nucleic acid fragment wherein one or more nucleotides in the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178 is changed from that selected from the group consisting of the chosen sequence to a different nucleotide provided that no more than 15% of the nucleotides are so changed.


[0048] One aspect of the invention pertains to isolated nucleic acid molecules that encode NOVX polypeptides or biologically active portions thereof. Also included in the invention are nucleic acid fragments sufficient for use as hybridization probes to identify NOVX-encoding nucleic acids (e.g., NOVX mRNAs) and fragments for use as PCR primers for the amplification and/or mutation of NOVX nucleic acid molecules. As used herein, the term “nucleic acid molecule” is intended to include DNA molecules (e.g., cDNA or genomic DNA), RNA molecules (e.g., mRNA), analogs of the DNA or RNA generated using nucleotide analogs, and derivatives, fragments and homologs thereof. The nucleic acid molecule may be single-stranded or double-stranded, but preferably is comprised double-stranded DNA.


[0049] An NOVX nucleic acid can encode a mature NOVX polypeptide. As used herein, a “mature” form of a polypeptide or protein disclosed in the present invention is the product of a naturally occurring polypeptide or precursor form or proprotein. The naturally occurring polypeptide, precursor or proprotein includes, by way of nonlimiting example, the full-length gene product, encoded by the corresponding gene. Alternatively, it may be defined as the polypeptide, precursor or proprotein encoded by an ORF described herein. The product “mature” form arises, again by way of nonlimiting example, as a result of one or more naturally occurring processing steps as they may take place within the cell, or host cell, in which the gene product arises. Examples of such processing steps leading to a “mature” form of a polypeptide or protein include the cleavage of the N-terminal methionine residue encoded by the initiation codon of an ORF, or the proteolytic cleavage of a signal peptide or leader sequence. Thus a mature form arising from a precursor polypeptide or protein that has residues 1 to N, where residue 1 is the N-terminal methionine, would have residues 2 through N remaining after removal of the N-terminal methionine. Alternatively, a mature form arising from a precursor polypeptide or protein having residues 1 to N, in which an N-terminal signal sequence from residue 1 to residue M is cleaved, would have the residues from residue M+1 to residue N remaining. Further as used herein, a “mature” form of a polypeptide or protein may arise from a step of post-translational modification other than a proteolytic cleavage event. Such additional processes include, by way of non-limiting example, glycosylation, myristoylation or phosphorylation. In general, a mature polypeptide or protein may result from the operation of only one of these processes, or a combination of any of them.


[0050] The term “probes”, as utilized herein, refers to nucleic acid sequences of variable length, preferably between at least about 10 nucleotides (nt), 100 nt, or as many as approximately, e.g., 6,000 nt, depending upon the specific use. Probes are used in the detection of identical, similar, or complementary nucleic acid sequences. Longer length probes are generally obtained from a natural or recombinant source, are highly specific, and much slower to hybridize than shorter-length oligomer probes. Probes may be single- or double-stranded and designed to have specificity in PCR, membrane-based hybridization technologies, or ELISA-like technologies.


[0051] The term “isolated” nucleic acid molecule, as utilized herein, is one, which is separated from other nucleic acid molecules which are present in the natural source of the nucleic acid. Preferably, an “isolated” nucleic acid is free of sequences which naturally flank the nucleic acid (i.e., sequences located at the 5′- and 3′-termini of the nucleic acid) in the genomic DNA of the organism from which the nucleic acid is derived. For example, in various embodiments, the isolated NOVX nucleic acid molecules can contain less than about 5 kb, 4 kb, 3 kb, 2 kb, 1 kb, 0.5 kb or 0.1 kb of nucleotide sequences which naturally flank the nucleic acid molecule in genomic DNA of the cell/tissue from which the nucleic acid is derived (e.g., brain, heart, liver, spleen, etc.). Moreover, an “isolated” nucleic acid molecule, such as a cDNA molecule, can be substantially free of other cellular material or culture medium when produced by recombinant techniques, or of chemical precursors or other chemicals when chemically synthesized.


[0052] A nucleic acid molecule of the invention, e.g., a nucleic acid molecule having the nucleotide sequence SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178, or a complement of this aforementioned nucleotide sequence, can be isolated using standard molecular biology techniques and the sequence information provided herein. Using all or a portion of the nucleic acid sequence of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178 as a hybridization probe, NOVX molecules can be isolated using standard hybridization and cloning techniques (e.g., as described in Sambrook, et al., (eds.), MOLECULAR CLONING: A LABORATORY MANUAL 2nd Ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989; and Ausubel, et al., (eds.), CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, New York, N.Y., 1993.)


[0053] A nucleic acid of the invention can be amplified using cDNA, mRNA or alternatively, genomic DNA, as a template and appropriate oligonucleotide primers according to standard PCR amplification techniques. The nucleic acid so amplified can be cloned into an appropriate vector and characterized by DNA sequence analysis. Furthermore, oligonucleotides corresponding to NOVX nucleotide sequences can be prepared by standard synthetic techniques, erg., using an automated DNA synthesizer.


[0054] As used herein, the term “oligonucleotide” refers to a series of linked nucleotide residues, which oligonucleotide has a sufficient number of nucleotide bases to be used in a PCR reaction. A short oligonucleotide sequence may be based on, or designed from, a genomic or cDNA sequence and is used to amplify, confirm, or reveal the presence of an identical, similar or complementary DNA or RNA in a particular cell or tissue. Oligonucleotides comprise portions of a nucleic acid sequence having about 10 nt, 50 nt, or 100 nt in length, preferably about 15 nt to 30 nt in length. In one embodiment of the invention, an oligonucleotide comprising a nucleic acid molecule less than 100 nt in length would further comprise at least 6 contiguous nucleotides SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178, or a complement thereof. Oligonucleotides may be chemically synthesized and may also be used as probes.


[0055] In another embodiment, an isolated nucleic acid molecule of the invention comprises a nucleic acid molecule that is a complement of the nucleotide from the group consisting of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178, or a portion of this nucleotide sequence (e.g., a fragment that can be used as a probe or primer or a fragment encoding a biologically-active portion of an NOVX polypeptide). A nucleic acid molecule that is complementary to the nucleotide sequence from the group consisting of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178 is one that is sufficiently complementary to the nucleotide sequence from the group consisting of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178 that it can hydrogen bond with little or no mismatches to the nucleotide sequence from the group consisting of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178, thereby forming a stable duplex.


[0056] As used herein, the term “complementary” refers to Watson-Crick or Hoogsteen base pairing between nucleotides units of a nucleic acid molecule, and the term “binding” means the physical or chemical interaction between two polypeptides or compounds or associated polypeptides or compounds or combinations thereof. Binding includes ionic, non-ionic, van der Waals, hydrophobic interactions, and the like. A physical interaction can be either direct or indirect. Indirect interactions may be through or due to the effects of another polypeptide or compound. Direct binding refers to interactions that do not take place through, or due to, the effect of another polypeptide or compound, but instead are without other substantial chemical intermediates.


[0057] Fragments provided herein are defined as sequences of at least 6 (contiguous) nucleic acids or at least 4 (contiguous) amino acids, a length sufficient to allow for specific hybridization in the case of nucleic acids or for specific recognition of an epitope in the case of amino acids, respectively, and are at most some portion less than a full length sequence. Fragments may be derived from any contiguous portion of a nucleic acid or amino acid sequence of choice. Derivatives are nucleic acid sequences or amino acid sequences formed from the native compounds either directly or by modification or partial substitution. Analogs are nucleic acid sequences or amino acid sequences that have a structure similar to, but not identical to, the native compound but differs from it in respect to certain components or side chains. Analogs may be synthetic or from a different evolutionary origin and may have a similar or opposite metabolic activity compared to wild type. Homologs are nucleic acid sequences or amino acid sequences of a particular gene that are derived from different species.


[0058] A full-length NOVX clone is identified as containing an ATG translation start codon and an in-frame stop codon. Any disclosed NOVX nucleotide sequence lacking an ATG start codon therefore encodes a truncated C-terminal fragment of the respective NOVX polypeptide, and requires that the corresponding full-length cDNA extend in the 5′ direction of the disclosed sequence. Any disclosed NOVX nucleotide sequence lacking an in-frame stop codon similarly encodes a truncated N-terminal fragment of the respective NOVX polypeptide, and requires that the corresponding full-length cDNA extend in the 3′ direction of the disclosed sequence.


[0059] Derivatives and analogs may be full length or other than full length, if the derivative or analog contains a modified nucleic acid or amino acid, as described below. Derivatives or analogs of the nucleic acids or proteins of the invention include, but are not limited to, molecules comprising regions that are substantially homologous to the nucleic acids or proteins of the invention, in various embodiments, by at least about 70%, 80%, or 95% identity (with a preferred identity of 80-95%) over a nucleic acid or amino acid sequence of identical size or when compared to an aligned sequence in which the alignment is done by a computer homology program known in the art, or whose encoding nucleic acid is capable of hybridizing to the complement of a sequence encoding the aforementioned proteins under stringent, moderately stringent, or low stringent conditions. See e.g. Ausubel, et al., CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, New York, N.Y., 1993, and below.


[0060] A “homologous nucleic acid sequence” or “homologous amino acid sequence,” or variations thereof, refer to sequences characterized by a homology at the nucleotide level or amino acid level as discussed above. Homologous nucleotide sequences encode those sequences coding for isoforms of NOVX polypeptides. Isoforms can be expressed in different tissues of the same organism as a result of, for example, alternative splicing of RNA. Alternatively, isoforms can be encoded by different genes. In the invention, homologous nucleotide sequences include nucleotide sequences encoding for an NOVX polypeptide of species other than humans, including, but not limited to: vertebrates, and thus can include, e.g., frog, mouse, rat, rabbit, dog, cat cow, horse, and other organisms. Homologous nucleotide sequences also include, but are not limited to, naturally occurring allelic variations and mutations of the nucleotide sequences set forth herein. A homologous nucleotide sequence does not, however, include the exact nucleotide sequence encoding human NOVX protein. Homologous nucleic acid sequences include those nucleic acid sequences that encode conservative amino acid substitutions (see below) in SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178, as well as a polypeptide possessing NOVX biological activity. Various biological activities of the NOVX proteins are described below.


[0061] An NOVX polypeptide is encoded by the open reading frame (“ORF”) of an NOVX nucleic acid. An ORF corresponds to a nucleotide sequence that could potentially be translated into a polypeptide. A stretch of nucleic acids comprising an ORF is uninterrupted by a stop codon. An ORF that represents the coding sequence for a full protein begins with an ATG “start” codon and terminates with one of the three “stop” codons, namely, TAA, TAG, or TGA. For the purposes of this invention, an ORF may be any part of a coding sequence, with or without a start codon, a stop codon, or both. For an ORF to be considered as a good candidate for coding for a bonafide cellular protein, a minimum size requirement is often set, e.g., a stretch of DNA that would encode a protein of 50 amino acids or more.


[0062] The nucleotide sequences determined from the cloning of the human NOVX genes allows for the generation of probes and primers designed for use in identifying and/or cloning NOVX homologues in other cell types, e.g. from other tissues, as well as NOVX homologues from other vertebrates. The probe/primer typically comprises substantially purified oligonucleotide. The oligonucleotide typically comprises a region of nucleotide sequence that hybridizes under stringent conditions to at least about 12, 25, 50, 100, 150, 200, 250, 300, 350 or 400 consecutive sense strand nucleotide sequence SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178; or an anti-sense strand nucleotide sequence of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178.


[0063] Probes based on the human NOVX nucleotide sequences can be used to detect transcripts or genomic sequences encoding the same or homologous proteins. In various embodiments, the probe further comprises a label group attached thereto, e.g. the label group can be a radioisotope, a fluorescent compound, an enzyme, or an enzyme co-factor. Such probes can be used as a part of a diagnostic test kit for identifying cells or tissues which mis-express an NOVX protein, such as by measuring a level of an NOVX-encoding nucleic acid in a sample of cells from a subject e.g., detecting NOVX mRNA levels or determining whether a genomic NOVX gene has been mutated or deleted.


[0064] “A polypeptide having a biologically-active portion of an NOVX polypeptide” refers to polypeptides exhibiting activity similar, but not necessarily identical to, an activity of a polypeptide of the invention, including mature forms, as measured in a particular biological assay, with or without dose dependency. A nucleic acid fragment encoding a “biologically-active portion of NOVX” can be prepared by isolating a portion SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178, that encodes a polypeptide having an NOVX biological activity (the biological activities of the NOVX proteins are described below), expressing the encoded portion of NOVX protein (e.g., by recombinant expression in vitro) and assessing the activity of the encoded portion of NOVX.


[0065] NOVX Nucleic Acid and Polypeptide Variants


[0066] The invention further encompasses nucleic acid molecules that differ from the nucleotide sequences shown in SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178 due to degeneracy of the genetic code and thus encode the same NOVX proteins as that encoded by the nucleotide sequences shown in SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178. In another embodiment, an isolated nucleic acid molecule of the invention has a nucleotide sequence encoding a protein having an amino acid sequence shown in SEQ ID NO: 2n, wherein n is an integer between 1 and 178.


[0067] In addition to the human NOVX nucleotide sequences shown in SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178, it will be appreciated by those skilled in the art that DNA sequence polymorphisms that lead to changes in the amino acid sequences of the NOVX polypeptides may exist within a population (e.g., the human population). Such genetic polymorphism in the NOVX genes may exist among individuals within a population due to natural allelic variation. As used herein, the terms “gene” and “recombinant gene” refer to nucleic acid molecules comprising an open reading frame (ORF) encoding an NOVX protein, preferably a vertebrate NOVX protein. Such natural allelic variations can typically result in 1-5% variance in the nucleotide sequence of the NOVX genes. Any and all such nucleotide variations and resulting amino acid polymorphisms in the NOVX polypeptides, which are the result of natural allelic variation and that do not alter the functional activity of the NOVX polypeptides, are intended to be within the scope of the invention.


[0068] Moreover, nucleic acid molecules encoding NOVX proteins from other species, and thus that have a nucleotide sequence that differs from the human SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178 are intended to be within the scope of the invention. Nucleic acid molecules corresponding to natural allelic variants and homologues of the NOVX cDNAs of the invention can be isolated based on their homology to the human NOVX nucleic acids disclosed herein using the human cDNAs, or a portion thereof, as a hybridization probe according to standard hybridization techniques under stringent hybridization conditions.


[0069] Accordingly, in another embodiment, an isolated nucleic acid molecule of the invention is at least 6 nucleotides in length and hybridizes under stringent conditions to the nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178. In another embodiment, the nucleic acid is at least 10, 25, 50, 100, 250, 500, 750, 1000, 1500, or 2000 or more nucleotides in length. In yet another embodiment, an isolated nucleic acid molecule of the invention hybridizes to the coding region. As used herein, the term “hybridizes under stringent conditions” is intended to describe conditions for hybridization and washing under which nucleotide sequences at least 60% homologous to each other typically remain hybridized to each other.


[0070] Homologs (i.e., nucleic acids encoding NOVX proteins derived from species other than human) or other related sequences (e.g., paralogs) can be obtained by low, moderate or high stringency hybridization with all or a portion of the particular human sequence as a probe using methods well known in the art for nucleic acid hybridization and cloning.


[0071] As used herein, the phrase “stringent hybridization conditions” refers to conditions under which a probe, primer or oligonucleotide will hybridize to its target sequence, but to no other sequences. Stringent conditions are sequence-dependent and will be different in different circumstances. Longer sequences hybridize specifically at higher temperatures than shorter sequences. Generally, stringent conditions are selected to be about 5° C. lower than the thermal melting point (Tm) for the specific sequence at a defined ionic strength and pH. The Tm is the temperature (under defined ionic strength, pH and nucleic acid concentration) at which 50% of the probes complementary to the target sequence hybridize to the target sequence at equilibrium. Since the target sequences are generally present at excess, at Tm, 50% of the probes are occupied at equilibrium. Typically, stringent conditions will be those in which the salt concentration is less than about 1.0 M sodium ion, typically about 0.01 to 1.0 M sodium ion (or other salts) at


[0072] pH 7.0 to 8.3 and the temperature is at least about 30° C. for short probes, primers or oligonucleotides (e.g., 10 nt to 50 nt) and at least about 60° C. for longer probes, primers and oligonucleotides. Stringent conditions may also be achieved with the addition of destabilizing agents, such as formamide.


[0073] Stringent conditions are known to those skilled in the art and can be found in Ausubel, et al., (eds.), CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, N.Y. (1989), 6.3.1-6.3.6. Preferably, the conditions are such that sequences at least about 65%, 70%, 75%, 85%, 90%, 95%, 98%, or 99% homologous to each other typically remain hybridized to each other. A non-limiting example of stringent hybridization conditions are hybridization in a high salt buffer comprising 6×SSC, 50 mM Tris-HCl (pH 7.5), 1 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.02% BSA, and 500 mg/ml denatured salmon sperm DNA at 65° C., followed by one or more washes in 0.2×SSC, 0.01% BSA at 50° C. An isolated nucleic acid molecule of the invention that hybridizes under stringent conditions to the sequences SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178, corresponds to a naturally-occurring nucleic acid molecule. As used herein, a “naturally-occurring” nucleic acid molecule refers to an RNA or DNA molecule having a nucleotide sequence that occurs in nature (e.g., encodes a natural protein).


[0074] In a second embodiment, a nucleic acid sequence that is hybridizable to the nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178, or fragments, analogs or derivatives thereof, under conditions of moderate stringency is provided. A non-limiting example of moderate stringency hybridization conditions are hybridization in 6×SSC, 5× Denhardt's solution, 0.5% SDS and 100 mg/ml denatured salmon sperm DNA at 55° C., followed by one or more washes in 1×SSC, 0.1% SDS at 37° C. Other conditions of moderate stringency that may be used are well-known within the art. See, e.g., Ausubel, et al. (eds.), 1993, CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, NY, and Kriegler, 1990; GENE TRANSFER AND EXPRESSION, A LABORATORY MANUAL, Stockton Press, NY.


[0075] In a third embodiment, a nucleic acid that is hybridizable to the nucleic acid molecule comprising the nucleotide sequences SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178, or fragments, analogs or derivatives thereof, under conditions of low stringency, is provided. A non-limiting example of low stringency hybridization conditions are hybridization in 35% formamide, 5×SSC, 50 mM Tris-HCl (pH 7.5), 5 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.2% BSA, 100 mg/ml denatured salmon sperm DNA, 10% (wt/vol) dextran sulfate at 40° C., followed by one or more washes in 2×SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS at 50° C. Other conditions of low stringency that may be used are well known in the art (e.g., as employed for cross-species hybridizations). See, e.g., Ausubel, et al. (eds.), 1993, CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, NY, and Kriegler, 1990, GENE TRANSFER AND EXPRESSION, A LABORATORY MANUAL, Stockton Press, NY; Shilo and Weinberg, 1981. Proc Natl Acad Sci USA 78: 6789-6792.


[0076] Conservative Mutations


[0077] In addition to naturally-occurring allelic variants of NOVX sequences that may exist in the population, the skilled artisan will further appreciate that changes can be introduced by mutation into the nucleotide sequences SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178, thereby leading to changes in the amino acid sequences of the encoded NOVX proteins, without altering the functional ability of said NOVX proteins. For example, nucleotide substitutions leading to amino acid substitutions at “non-essential” amino acid residues can be made in the sequence SEQ ID NO: 2n, wherein n is an integer between 1 and 178. A “non-essential” amino acid residue is a residue that can be altered from the wild-type sequences of the NOVX proteins without altering their biological activity, whereas an “essential” amino acid residue is required for such biological activity. For example, amino acid residues that are conserved among the NOVX proteins of the invention are predicted to be particularly non-amenable to alteration. Amino acids for which conservative substitutions can be made are well-known within the art.


[0078] Another aspect of the invention pertains to nucleic acid molecules encoding NOVX proteins that contain changes in amino acid residues that are not essential for activity. Such NOVX proteins differ in amino acid sequence from SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178 yet retain biological activity. In one embodiment, the isolated nucleic acid molecule comprises a nucleotide sequence encoding a protein, wherein the protein comprises an amino acid sequence at least about 45% homologous to the amino acid sequences SEQ ID NO: 2n, wherein n is an integer between 1 and 178. Preferably, the protein encoded by the nucleic acid molecule is at least about 60% homologous to SEQ ID NO: 2n, wherein n is an integer between 1 and 178; more preferably at least about 70% homologous SEQ ID NO: 2n, wherein n is an integer between 1 and 178; still more preferably at least about 80% homologous to SEQ ID NO: 2n, wherein n is an integer between 1 and 178; even more preferably at least about 90% homologous to SEQ ID NO: 2n, wherein n is an integer between 1 and 178; and most preferably at least about 95% homologous to SEQ ID NO: 2n, wherein n is an integer between 1 and 178.


[0079] An isolated nucleic acid molecule encoding an NOVX protein homologous to the protein of SEQ ID NO: 2n, wherein n is an integer between 1 and 178 can be created by introducing one or more nucleotide substitutions, additions or deletions into the nucleotide sequence of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178, such that one or more amino acid substitutions, additions or deletions are introduced into the encoded protein.


[0080] Mutations can be introduced into SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178 standard techniques, such as site-directed mutagenesis and PCR-mediated mutagenesis. Preferably, conservative amino acid substitutions are made at one or more predicted, non-essential amino acid residues. A “conservative amino acid substitution” is one in which the amino acid residue is replaced with an amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined within the art. These families include amino acids with basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine). Thus, a predicted non-essential amino acid residue in the NOVX protein is replaced with another amino acid residue from the same side chain family. Alternatively, in another embodiment, mutations can be introduced randomly along all or part of an NOVX coding sequence, such as by saturation mutagenesis, and the resultant mutants can be screened for NOVX biological activity to identify mutants that retain activity. Following mutagenesis SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178, the encoded protein can be expressed by any recombinant technology known in the art and the activity of the protein can be determined.


[0081] The relatedness of amino acid families may also be determined based on side chain interactions. Substituted amino acids may be fully conserved “strong” residues or fully conserved “weak” residues. The “strong” group of conserved amino acid residues may be any one of the following groups: STA, NEQK, NHQK, NDEQ, QHRK, MILV, MILF, HY, FYW, wherein the single letter amino acid codes are grouped by those amino acids that may be substituted for each other. Likewise, the “weak” group of conserved residues may be any one of the following: CSA, ATV, SAG, STNK, STPA, SGND, SNDEQK, NDEQHK, NEQHRK, HFY, wherein the letters within each group represent the single letter amino acid code.


[0082] In one embodiment, a mutant NOVX protein can be assayed for (i) the ability to form protein:protein interactions with other NOVX proteins, other cell-surface proteins, or biologically-active portions thereof, (ii) complex formation between a mutant NOVX protein and an NOVX ligand; or (iii) the ability of a mutant NOVX protein to bind to an intracellular target protein or biologically-active portion thereof; (e.g. avidin proteins).


[0083] In yet another embodiment, a mutant NOVX protein can be assayed for the ability to regulate a specific biological function (e.g., regulation of insulin release).


[0084] Antisense Nucleic Acids


[0085] Another aspect of the invention pertains to isolated antisense nucleic acid molecules that are hybridizable to or complementary to the nucleic acid molecule comprising the nucleotide sequence of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178, or fragments, analogs or derivatives thereof. An “antisense” nucleic acid comprises a nucleotide sequence that is complementary to a “sense” nucleic acid encoding a protein (e.g., complementary to the coding strand of a double-stranded cDNA molecule or complementary to an mRNA sequence). In specific aspects, antisense nucleic acid molecules are provided that comprise a sequence complementary to at least about 10, 25, 50, 100, 250 or 500 nucleotides or an entire NOVX coding strand, or to only a portion thereof. Nucleic acid molecules encoding fragments, homologs, derivatives and analogs of an NOVX protein of SEQ ID NO: 2n, wherein n is an integer between 1 and 178, or antisense nucleic acids complementary to an NOVX nucleic acid sequence of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178, are additionally provided.


[0086] In one embodiment, an antisense nucleic acid molecule is antisense to a “coding region” of the coding strand of a nucleotide sequence encoding an NOVX protein. The term “coding region” refers to the region of the nucleotide sequence comprising codons which are translated into amino acid residues. In another embodiment, the antisense nucleic acid molecule is antisense to a “noncoding region” of the coding strand of a nucleotide sequence encoding the NOVX protein. The term “noncoding region” refers to 5′ and 3′ sequences which flank the coding region that are not translated into amino acids (i.e., also referred to as 5′ and 3′ untranslated regions).


[0087] Given the coding strand sequences encoding the NOVX protein disclosed herein, antisense nucleic acids of the invention can be designed according to the rules of Watson and Crick or Hoogsteen base pairing. The antisense nucleic acid molecule can be complementary to the entire coding region of NOVX mRNA, but more preferably is an oligonucleotide that is antisense to only a portion of the coding or noncoding region of NOVX mRNA. For example, the antisense oligonucleotide can be complementary to the region surrounding the translation start site of NOVX mRNA. An antisense oligonucleotide can be, for example, about 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50 nucleotides in length. An antisense nucleic acid of the invention can be constructed using chemical synthesis or enzymatic ligation reactions using procedures known in the art. For example, an antisense nucleic acid (e.g., an antisense oligonucleotide) can be chemically synthesized using naturally-occurring nucleotides or variously modified nucleotides designed to increase the biological stability of the molecules or to increase the physical stability of the duplex formed between the antisense and sense nucleic acids (e.g., phosphorothioate derivatives and acridine substituted nucleotides can be used).


[0088] Examples of modified nucleotides that can be used to generate the antisense nucleic acid include: 5-fluorouracil, 5-bromouracil, 5-chlorouracil, 5-iodouracil, hypoxanthine, xanthine, 4-acetylcytosine, 5-(carboxyhydroxylmethyl) uracil, 5-carboxymethylaminomethyl-2-thiouridine, 5-carboxymethylaminomethyluracil, dihydrouracil, beta-D-galactosylqueosine, inosine, N6-isopentenyladenine, 1-methylguanine, 1-methylinosine, 2,2-dimethylguanine, 2-methyladenine, 2-methylguanine, 3-methylcytosine, 5-methylcytosine, N6-adenine, 7-methylguanine, 5-methylaminomethyluracil, 5-methoxyaminomethyl-2-thiouracil, beta-D-mannosylqueosine, 5′-methoxycarboxymethyluracil, 5-methoxyuracil, 2-methylthio-N-6-isopentenyladenine, uracil-5-oxyacetic acid (v), wybutoxosine, pseudouracil, queosine, 2-thiocytosine, 5-methyl-2-thiouracil, 2-thiouracil, 4-thiouracil, 5-methyluracil, uracil-5-oxyacetic acid methylester, uracil-5-oxyacetic acid (v), 5-methyl-2-thiouracil, 3-(3-amino-3-N-2-carboxypropyl) uracil, (acp3)w, and 2,6-diaminopurine. Alternatively, the antisense nucleic acid can be produced biologically using an expression vector into which a nucleic acid has been subcloned in an antisense orientation (i.e., RNA transcribed from the inserted nucleic acid will be of an antisense orientation to a target nucleic acid of interest, described further in the following subsection).


[0089] The antisense nucleic acid molecules of the invention are typically administered to a subject or generated in situ such that they hybridize with or bind to cellular mRNA and/or genomic DNA encoding an NOVX protein to thereby inhibit expression of the protein (e.g., by inhibiting transcription and/or translation). The hybridization can be by conventional nucleotide complementarity to form a stable duplex, or, for example, in the case of an antisense nucleic acid molecule that binds to DNA duplexes, through specific interactions in the major groove of the double helix. An example of a route of administration of antisense nucleic acid molecules of the invention includes direct injection at a tissue site. Alternatively, antisense nucleic acid molecules can be modified to target selected cells and then administered systemically. For example, for systemic administration, antisense molecules can be modified such that they specifically bind to receptors or antigens expressed on a selected cell surface (e.g., by linking the antisense nucleic acid molecules to peptides or antibodies that bind to cell surface receptors or antigens). The antisense nucleic acid molecules can also be delivered to cells using the vectors described herein. To achieve sufficient nucleic acid molecules, vector constructs in which the antisense nucleic acid molecule is placed under the control of a strong pol II or pol III promoter are preferred.


[0090] In yet another embodiment, the antisense nucleic acid molecule of the invention is an α-anomeric nucleic acid molecule. An α-anomeric nucleic acid molecule forms specific double-stranded hybrids with complementary RNA in which, contrary to the usual β-units, the strands run parallel to each other. See, e.g., Gaultier, et al., 1987. Nucl. Acids Res. 15: 6625-6641. The antisense nucleic acid molecule can also comprise a 2′-o-methylribonucleotide (See, e.g., Inoue, et al. 1987. Nucl. Acids Res. 15: 6131-6148) or a chimeric RNA-DNA analogue (See, e.g., Inoue, et al., 1987. FEBS Lett. 215: 327-330.


[0091] Ribozymes and PNA Moieties


[0092] Nucleic acid modifications include, by way of non-limiting example, modified bases, and nucleic acids whose sugar phosphate backbones are modified or derivatized. These modifications are carried out at least in part to enhance the chemical stability of the modified nucleic acid, such that they may be used, for example, as antisense binding nucleic acids in therapeutic applications in a subject.


[0093] In one embodiment, an antisense nucleic acid of the invention is a ribozyme. Ribozymes are catalytic RNA molecules with ribonuclease activity that are capable of cleaving a single-stranded nucleic acid, such as an mRNA, to which they have a complementary region. Thus, ribozymes (e.g., hammerhead ribozymes as described in Haselhoff and Gerlach 1988. Nature 334: 585-591) can be used to catalytically cleave NOVX mRNA transcripts to thereby inhibit translation of NOVX mRNA. A ribozyme having specificity for an NOVX-encoding nucleic acid can be designed based upon the nucleotide sequence of an NOVX cDNA disclosed herein (i.e., SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178). For example, a derivative of a Tetrahymena L-19 IVS RNA can be constructed in which the nucleotide sequence of the active site is complementary to the nucleotide sequence to be cleaved in an NOVX-encoding mRNA. See, e.g., U.S. Pat. No. 4,987,071 to Cech, et al. and U.S. Pat. No. 5,116,742 to Cech, et al. NOVX mRNA can also be used to select a catalytic RNA having a specific ribonuclease activity from a pool of RNA molecules. See, e.g., Bartel et al., (1993) Science 261:1411-1418.


[0094] Alternatively, NOVX gene expression can be inhibited by targeting nucleotide sequences complementary to the regulatory region of the NOVX nucleic acid (e.g., the NOVX promoter and/or enhancers) to form triple helical structures that prevent transcription of the NOVX gene in target cells. See, e.g., Helene, 1991. Anticancer Drug Des. 6: 569-84; Helene, et al. 1992. Ann. N. Y Acad. Sci. 660: 27-36; Maher, 1992. Bioassays 14: 807-15.


[0095] In various embodiments, the NOVX nucleic acids can be modified at the base moiety, sugar moiety or phosphate backbone to improve, e.g., the stability, hybridization, or solubility of the molecule. For example, the deoxyribose phosphate backbone of the nucleic acids can be modified to generate peptide nucleic acids. See, e.g., Hyrup, et al., 1996. Bioorg Med Chem 4: 5-23. As used herein, the terms “peptide nucleic acids” or “PNAs” refer to nucleic acid mimics (e.g., DNA mimics) in which the deoxyribose phosphate backbone is replaced by a pseudopeptide backbone and only the four natural nucleobases are retained. The neutral backbone of PNAs has been shown to allow for specific hybridization to DNA and RNA under conditions of low ionic strength. The synthesis of PNA oligomers can be performed using standard solid phase peptide synthesis protocols as described in Hyrup, et al., 1996. supra; Perry-O'Keefe, et al., 1996. Proc. Natl. Acad. Sci. USA 93:14670-14675.


[0096] PNAs of NOVX can be used in therapeutic and diagnostic applications. For example, PNAs can be used as antisense or antigene agents for sequence-specific modulation of gene expression by, e.g., inducing transcription or translation arrest or inhibiting replication. PNAs of NOVX can also be used, for example, in the analysis of single base pair mutations in a gene (e.g., PNA directed PCR clamping; as artificial restriction enzymes when used in combination with other enzymes, e.g., S1 nucleases (See, Hyrup, et al., 1996.supra); or as probes or primers for DNA sequence and hybridization (See, Hyrup, et al., 1996, supra; Perry-O'Keefe, et al., 1996. supra).


[0097] In another embodiment, PNAs of NOVX can be modified, e.g., to enhance their stability or cellular uptake, by attaching lipophilic or other helper groups to PNA, by the formation of PNA-DNA chimeras, or by the use of liposomes or other techniques of drug delivery known in the art. For example, PNA-DNA chimeras of NOVX can be generated that may combine the advantageous properties of PNA and DNA. Such chimeras allow DNA recognition enzymes (e.g., RNase H and DNA polymerases) to interact with the DNA portion while the PNA portion would provide high binding affinity and specificity. PNA-DNA chimeras can be linked using linkers of appropriate lengths selected in terms of base stacking, number of bonds between the nucleobases, and orientation (see, Hyrup, et al., 1996. supra). The synthesis of PNA-DNA chimeras can be performed as described in Hyrup, et al., 1996. supra and Finn, et al., 1996. Nucl Acids Res 24: 3357-3363. For example, a DNA chain can be synthesized on a solid support using standard phosphoramidite coupling chemistry, and modified nucleoside analogs, e.g., 5′-(4-methoxytrityl)amino-5′-deoxy-thymidine phosphoramidite, can be used between the PNA and the 5′ end of DNA. See, e.g., Mag, et al., 1989. Nucl Acid Res 17: 5973-5988. PNA monomers are then coupled in a stepwise manner to produce a chimeric molecule with a 5′ PNA segment and a 3′ DNA segment. See, e.g., Finn, et al., 1996. supra. Alternatively, chimeric molecules can be synthesized with a 5′ DNA segment and a 3′ PNA segment. See, e.g., Petersen, et al., 1975. Bioorg. Med. Chem. Lett. 5: 1119-11124.


[0098] In other embodiments, the oligonucleotide may include other appended groups such as peptides (e.g., for targeting host cell receptors in vivo), or agents facilitating transport across the cell membrane (see, e.g., Letsinger, et al., 1989. Proc. Natl. Acad. Sci. U.S.A. 86: 6553-6556; Lemaitre, et al., 1987. Proc. Natl. Acad. Sci. 84: 648-652; PCT Publication No. WO88/09810) or the blood-brain barrier (see, e.g., PCT Publication No. WO 89/10134). In addition, oligonucleotides can be modified with hybridization triggered cleavage agents (see, e.g., Krol, et al., 1988. BioTechniques 6:958-976) or intercalating agents (see, e.g., Zon, 1988. Pharm. Res. 5: 539-549). To this end, the oligonucleotide may be conjugated to another molecule, e.g., a peptide, a hybridization triggered cross-linking agent, a transport agent, a hybridization-triggered cleavage agent, and the like.


[0099] NOVX Polypeptides


[0100] A polypeptide according to the invention includes a polypeptide including the amino acid sequence of NOVX polypeptides whose sequences are provided in SEQ ID NO: 2n, wherein n is an integer between 1 and 178. The invention also includes a mutant or variant protein any of whose residues may be changed from the corresponding residues shown in SEQ ID NO: 2n, wherein n is an integer between 1 and 178 while still encoding a protein that maintains its NOVX activities and physiological functions, or a functional fragment thereof.


[0101] In general, an NOVX variant that preserves NOVX-like function includes any variant in which residues at a particular position in the sequence have been substituted by other amino acids, and further include the possibility of inserting an additional residue or residues between two residues of the parent protein as well as the possibility of deleting one or more residues from the parent sequence. Any amino acid substitution, insertion, or deletion is encompassed by the invention. In favorable circumstances, the substitution is a conservative substitution as defined above.


[0102] One aspect of the invention pertains to isolated NOVX proteins, and biologically-active portions thereof, or derivatives, fragments, analogs or homologs thereof. Also provided are polypeptide fragments suitable for use as immunogens to raise anti-NOVX antibodies. In one embodiment, native NOVX proteins can be isolated from cells or tissue sources by an appropriate purification scheme using standard protein purification techniques. In another embodiment, NOVX proteins are produced by recombinant DNA techniques. Alternative to recombinant expression, an NOVX protein or polypeptide can be synthesized chemically using standard peptide synthesis techniques.


[0103] An “isolated” or “purified” polypeptide or protein or biologically-active portion thereof is substantially free of cellular material or other contaminating proteins from the cell or tissue source from which the NOVX protein is derived, or substantially free from chemical precursors or other chemicals when chemically synthesized. The language “substantially free of cellular material” includes preparations of NOVX proteins in which the protein is separated from cellular components of the cells from which it is isolated or recombinantly-produced. In one embodiment, the language “substantially free of cellular material” includes preparations of NOVX proteins having less than about 30% (by dry weight) of non-NOVX proteins (also referred to herein as a “contaminating protein”), more preferably less than about 20% of non-NOVX proteins, still more preferably less than about 10% of non-NOVX proteins, and most preferably less than about 5% of non-NOVX proteins. When the NOVX protein or biologically-active portion thereof is recombinantly-produced, it is also preferably substantially free of culture medium, i.e., culture medium represents less than about 20%, more preferably less than about 10%, and most preferably less than about 5% of the volume of the NOVX protein preparation.


[0104] The language “substantially free of chemical precursors or other chemicals” includes preparations of NOVX proteins in which the protein is separated from chemical precursors or other chemicals that are involved in the synthesis of the protein. In one embodiment, the language “substantially free of chemical precursors or other chemicals” includes preparations of NOVX proteins having less than about 30% (by dry weight) of chemical precursors or non-NOVX chemicals, more preferably less than about 20% chemical precursors or non-NOVX chemicals, still more preferably less than about 10% chemical precursors or non-NOVX chemicals, and most preferably less than about 5% chemical precursors or non-NOVX chemicals.


[0105] Biologically-active portions of NOVX proteins include peptides comprising amino acid sequences sufficiently homologous to or derived from the amino acid sequences of the NOVX proteins (e.g., the amino acid sequence shown in SEQ ID NO: 2n, wherein n is an integer between 1 and 178) that include fewer amino acids than the full-length NOVX proteins, and exhibit at least one activity of an NOVX protein. Typically, biologically-active portions comprise a domain or motif with at least one activity of the NOVX protein. A biologically-active portion of an NOVX protein can be a polypeptide which is, for example, 10, 25, 50, 100 or more amino acid residues in length.


[0106] Moreover, other biologically-active portions, in which other regions of the protein are deleted, can be prepared by recombinant techniques and evaluated for one or more of the functional activities of a native NOVX protein.


[0107] In an embodiment, the NOVX protein has an amino acid sequence shown SEQ ID NO: 2n, wherein n is an integer between 1 and 178. In other embodiments, the NOVX protein is substantially homologous to SEQ ID NO: 2n, wherein n is an integer between 1 and 178, and retains the functional activity of the protein of SEQ ID NO: 2n, wherein n is an integer between 1 and 178, yet differs in amino acid sequence due to natural allelic variation or mutagenesis, as described in detail, below. Accordingly, in another embodiment, the NOVX protein is a protein that comprises an amino acid sequence at least about 45% homologous to the amino acid sequence SEQ ID NO: 2n, wherein n is an integer between 1 and 178, and retains the functional activity of the NOVX proteins of SEQ ID NO: 2n, wherein n is an integer between 1 and 178.


[0108] Determining Homology Between Two or More Sequences


[0109] To determine the percent homology of two amino acid sequences or of two nucleic acids, the sequences are aligned for optimal comparison purposes (e.g., gaps can be introduced in the sequence of a first amino acid or nucleic acid sequence for optimal alignment with a second amino or nucleic acid sequence). The amino acid residues or nucleotides at corresponding amino acid positions or nucleotide positions are then compared. When a position in the first sequence is occupied by the same amino acid residue or nucleotide as the corresponding position in the second sequence, then the molecules are homologous at that position (i.e., as used herein amino acid or nucleic acid “homology” is equivalent to amino acid or nucleic acid “identity”).


[0110] The nucleic acid sequence homology may be determined as the degree of identity between two sequences. The homology may be determined using computer programs known in the art, such as GAP software provided in the GCG program package. See, Needleman and Wunsch, 1970. J Mol Biol 48: 443-453. Using GCG GAP software with the following settings for nucleic acid sequence comparison: GAP creation penalty of 5.0 and GAP extension penalty of 0.3, the coding region of the analogous nucleic acid sequences referred to above exhibits a degree of identity preferably of at least 70%, 75%, 80%, 85%, 90%, 95%, 98%, or 99%, with the CDS (encoding) part of the DNA from the group consisting of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178.


[0111] The term “sequence identity” refers to the degree to which two polynucleotide or polypeptide sequences are identical on a residue-by-residue basis over a particular region of comparison. The term “percentage of sequence identity” is calculated by comparing two optimally aligned sequences over that region of comparison, determining the number of positions at which the identical nucleic acid base (e.g., A, T, C, G, U, or I, in the case of nucleic acids) occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the region of comparison (i.e., the window size), and multiplying the result by 100 to yield the percentage of sequence identity. The term “substantial identity” as used herein denotes a characteristic of a polynucleotide sequence, wherein the polynucleotide comprises a sequence that has at least 80 percent sequence identity, preferably at least 85 percent identity and often 90 to 95 percent sequence identity, more usually at least 99 percent sequence identity as compared to a reference sequence over a comparison region.


[0112] Chimeric and Fusion Proteins


[0113] The invention also provides NOVX chimeric or fusion proteins. As used herein, an A NOVX “chimeric protein” or “fusion protein” comprises an NOVX polypeptide operatively-linked to a non-NOVX polypeptide. An “NOVX polypeptide” refers to a polypeptide having an amino acid sequence corresponding to an NOVX protein SEQ ID NO: 2n, wherein n is an integer between 1 and 178, whereas a “non-NOVX polypeptide” refers to a polypeptide having an amino acid sequence corresponding to a protein that is not substantially homologous to the NOVX protein, e.g., a protein that is different from the NOVX protein and that is derived from the same or a different organism. Within an NOVX fusion protein the NOVX polypeptide can correspond to all or a portion of an NOVX protein. In one embodiment, an NOVX fusion protein comprises at least one biologically-active portion of an NOVX protein. In another embodiment, an NOVX fusion protein comprises at least two biologically-active portions of an NOVX protein. In yet another embodiment, an NOVX fusion protein comprises at least three biologically-active portions of an NOVX protein. Within the fusion protein, the term “operatively-linked” is intended to indicate that the NOVX polypeptide and the non-NOVX polypeptide are fused in-frame with one another. The non-NOVX polypeptide can be fused to the N-terminus or C-terminus of the NOVX polypeptide.


[0114] In one embodiment, the fusion protein is a GST-NOVX fusion protein in which the NOVX sequences are fused to the C-terminus of the GST (glutathione S-transferase) sequences. Such fusion proteins can facilitate the purification of recombinant NOVX polypeptides.


[0115] In another embodiment, the fusion protein is an NOVX protein containing a heterologous signal sequence at its N-terminus. In certain host cells (e.g., mammalian host cells), expression and/or secretion of NOVX can be increased through use of a heterologous signal sequence.


[0116] In yet another embodiment, the fusion protein is an NOVX-immunoglobulin fusion protein in which the NOVX sequences are fused to sequences derived from a member of the immunoglobulin protein family. The NOVX-immunoglobulin fusion proteins of the invention can be incorporated into pharmaceutical compositions and administered to a subject to inhibit an interaction between an NOVX ligand and an NOVX protein on the surface of a cell, to thereby suppress NOVX-mediated signal transduction in vivo. The NOVX-immunoglobulin fusion proteins can be used to affect the bioavailability of an NOVX cognate ligand. Inhibition of the NOVX ligand/NOVX interaction may be useful therapeutically for both the treatment of proliferative and differentiative disorders, as well as modulating (e.g. promoting or inhibiting) cell survival. Moreover, the NOVX-immunoglobulin fusion proteins of the invention can be used as immunogens to produce anti-NOVX antibodies in a subject, to purify NOVX ligands, and in screening assays to identify molecules that inhibit the interaction of NOVX with an NOVX ligand.


[0117] An NOVX chimeric or fusion protein of the invention can be produced by standard recombinant DNA techniques. For example, DNA fragments coding for the different polypeptide sequences are ligated together in-frame in accordance with conventional techniques, e.g., by employing blunt-ended or stagger-ended termini for ligation, restriction enzyme digestion to provide for appropriate termini, filling-in of cohesive ends as appropriate, alkaline phosphatase treatment to avoid undesirable joining, and enzymatic ligation. In another embodiment, the fusion gene can be synthesized by conventional techniques including automated DNA synthesizers. Alternatively, PCR amplification of gene fragments can be carried out using anchor primers that give rise to complementary overhangs between two consecutive gene fragments that can subsequently be annealed and reamplified to generate a chimeric gene sequence (see, e.g., Ausubel, et al. (eds.) CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, 1992). Moreover, many expression vectors are commercially available that already encode a fusion moiety (e.g., a GST polypeptide). An NOVX-encoding nucleic acid can be cloned into such an expression vector such that the fusion moiety is linked in-frame to the NOVX protein.


[0118] NOVX Agonists and Antagonists


[0119] The invention also pertains to variants of the NOVX proteins that function as either NOVX agonists (i.e., mimetics) or as NOVX antagonists. Variants of the NOVX protein can be generated by mutagenesis (e.g., discrete point mutation or truncation of the NOVX protein). An agonist of the NOVX protein can retain substantially the same, or a subset of, the biological activities of the naturally occurring form of the NOVX protein. An antagonist of the NOVX protein can inhibit one or more of the activities of the naturally occurring form of the NOVX protein by, for example, competitively binding to a downstream or upstream member of a cellular signaling cascade which includes the NOVX protein. Thus, specific biological effects can be elicited by treatment with a variant of limited function. In one embodiment, treatment of a subject with a variant having a subset of the biological activities of the naturally occurring form of the protein has fewer side effects in a subject relative to treatment with the naturally occurring form of the NOVX proteins.


[0120] Variants of the NOVX proteins that function as either NOVX agonists (i.e., mimetics) or as NOVX antagonists can be identified by screening combinatorial libraries of mutants (e.g., truncation mutants) of the NOVX proteins for NOVX protein agonist or antagonist activity. In one embodiment, a variegated library of NOVX variants is generated by combinatorial mutagenesis at the nucleic acid level and is encoded by a variegated gene library. A variegated library of NOVX variants can be produced by, for example, enzymatically ligating a mixture of synthetic oligonucleotides into gene sequences such that a degenerate set of potential NOVX sequences is expressible as individual polypeptides, or alternatively, as a set of larger fusion proteins (e.g., for phage display) containing the set of NOVX sequences therein. There are a variety of methods which can be used to produce libraries of potential NOVX variants from a degenerate oligonucleotide sequence. Chemical synthesis of a degenerate gene sequence can be performed in an automatic DNA synthesizer, and the synthetic gene then ligated into an appropriate expression vector. Use of a degenerate set of genes allows for the provision, in one mixture, of all of the sequences encoding the desired set of potential NOVX sequences. Methods for synthesizing degenerate oligonucleotides are well-known within the art. See, e.g., Narang, 1983. Tetrahedron 39: 3; Itakura, et al., 1984. Annu. Rev. Biochem. 53: 323; Itakura, et al., 1984. Science 198: 1056; Ike, et al., 1983. Nucl. Acids Res. 11: 477.


[0121] Polypeptide Libraries


[0122] In addition, libraries of fragments of the NOVX protein coding sequences can be used to generate a variegated population of NOVX fragments for screening and subsequent selection of variants of an NOVX protein. In one embodiment, a library of coding sequence fragments can be generated by treating a double stranded PCR fragment of an NOVX coding sequence with a nuclease under conditions wherein nicking occurs only about once per molecule, denaturing the double stranded DNA, renaturing the DNA to form double-stranded DNA that can include sense/antisense pairs from different nicked products, removing single stranded portions from reformed duplexes by treatment with S1 nuclease, and ligating the resulting fragment library into an expression vector. By this method, expression libraries can be derived which encodes N-terminal and internal fragments of various sizes of the NOVX proteins.


[0123] Various techniques are known in the art for screening gene products of combinatorial libraries made by point mutations or truncation, and for screening cDNA libraries for gene products having a selected property. Such techniques are adaptable for rapid screening of the gene libraries generated by the combinatorial mutagenesis of NOVX proteins. The most widely used techniques, which are amenable to high throughput analysis, for screening large gene libraries typically include cloning the gene library into replicable expression vectors, transforming appropriate cells with the resulting library of vectors, and expressing the combinatorial genes under conditions in which detection of a desired activity facilitates isolation of the vector encoding the gene whose product was detected. Recursive ensemble mutagenesis (REM), a new technique that enhances the frequency of functional mutants in the libraries, can be used in combination with the screening assays to identify NOVX variants. See, e.g., Arkin and Yourvan, 1992. Proc. Natl. Acad. Sci. USA 89: 7811-7815; Delgrave, et al., 1993. Protein Engineering 6:327-331.


[0124] NOVX Antibodies


[0125] The term “antibody” as used herein refers to immunoglobulin molecules and immunologically active portions of immunoglobulin (Ig) molecules, i.e., molecules that contain an antigen binding site that specifically binds (immunoreacts with) an antigen. Such antibodies include, but are not limited to, polyclonal, monoclonal, chimeric, single chain, Fab, Fab, and F(ab)2 fragments, and an Fab expression library. In general, antibody molecules obtained from humans relates to any of the classes IgG, IgM, IgA, IgE and IgD, which differ from one another by the nature of the heavy chain present in the molecule. Certain classes have subclasses as well, such as IgG1, IgG2, and others. Furthermore, in humans, the light chain may be a kappa chain or a lambda chain. Reference herein to antibodies includes a reference to all such classes, subclasses and types of human antibody species.


[0126] An isolated protein of the invention intended to serve as an antigen, or a portion or fragment thereof, can be used as an immunogen to generate antibodies that immunospecifically bind the antigen, using standard techniques for polyclonal and monoclonal antibody preparation. The full-length protein can be used or, alternatively, the invention provides antigenic peptide fragments of the antigen for use as immunogens. An antigenic peptide fragment comprises at least 6 amino acid residues of the amino acid sequence of the full length protein, such as an amino acid sequence shown in SEQ ID NO: 2n, wherein n is an integer between 1 and 178, and encompasses an epitope thereof such that an antibody raised against the peptide forms a specific immune complex with the full length protein or with any fragment that contains the epitope. Preferably, the antigenic peptide comprises at least 10 amino acid residues, or at least 15 amino acid residues, or at least 20 amino acid residues, or at least 30 amino acid residues. Preferred epitopes encompassed by the antigenic peptide are regions of the protein that are located on its surface; commonly these are hydrophilic regions.


[0127] In certain embodiments of the invention, at least one epitope encompassed by the antigenic peptide is a region of NOVX that is located on the surface of the protein, e.g., a hydrophilic region. A hydrophobicity analysis of the human NOVX protein sequence will indicate which regions of a NOVX polypeptide are particularly hydrophilic and, therefore, are likely to encode surface residues useful for targeting antibody production. As a means for targeting antibody production, hydropathy plots showing regions of hydrophilicity and hydrophobicity may be generated by any method well known in the art, including, for example, the Kyte Doolittle or the Hopp Woods methods, either with or without Fourier transformation. See, e.g., Hopp and Woods, 1981, Proc. Nat. Acad. Sci. USA 78: 3824-3828; Kyte and Doolittle 1982, J. Mol. Biol. 157: 105-142, each incorporated herein by reference in their entirety. Antibodies that are specific for one or more domains within an antigenic protein, or derivatives, fragments, analogs or homologs thereof, are also provided herein.


[0128] A protein of the invention, or a derivative, fragment, analog, homolog or ortholog thereof, may be utilized as an immunogen in the generation of antibodies that immunospecifically bind these protein components.


[0129] Various procedures known within the art may be used for the production of polyclonal or monoclonal antibodies directed against a protein of the invention, or against derivatives, fragments, analogs homologs or orthologs thereof (see, for example, Antibodies: A Laboratory Manual, Harlow E, and Lane D, 1988, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., incorporated herein by reference). Some of these antibodies are discussed below.


[0130] Polyclonal Antibodies


[0131] For the production of polyclonal antibodies, various suitable host animals (e.g., rabbit, goat, mouse or other mammal) may be immunized by one or more injections with the native protein, a synthetic variant thereof, or a derivative of the foregoing. An appropriate immunogenic preparation can contain, for example, the naturally occurring immunogenic protein, a chemically synthesized polypeptide representing the immunogenic protein, or a recombinantly expressed immunogenic protein. Furthermore, the protein may be conjugated to a second protein known to be immunogenic in the mammal being immunized. Examples of such immunogenic proteins include but are not limited to keyhole limpet hemocyanin, serum albumin, bovine thyroglobulin, and soybean trypsin inhibitor. The preparation can further include an adjuvant. Various adjuvants used to increase the immunological response include, but are not limited to, Freund's (complete and incomplete), mineral gels (e.g., aluminum hydroxide), surface active substances (e.g., lysolecithin, pluronic polyols, polyanions, peptides, oil emulsions, dinitrophenol, etc.), adjuvants usable in humans such as Bacille Calmette-Guerin and Corynebacterium parvum, or similar immunostimulatory agents. Additional examples of adjuvants which can be employed include MPL-TDM adjuvant (monophosphoryl Lipid A, synthetic trehalose dicorynomycolate).


[0132] The polyclonal antibody molecules directed against the immunogenic protein can be isolated from the mammal (e.g., from the blood) and further purified by well known techniques, such as affinity chromatography using protein A or protein G, which provide primarily the IgG fraction of immune serum. Subsequently, or alternatively, the specific antigen which is the target of the immunoglobulin sought, or an epitope thereof, may be immobilized on a column to purify the immune specific antibody by immunoaffinity chromatography. Purification of immunoglobulins is discussed, for example, by D. Wilkinson (The Scientist, published by The Scientist, Inc., Philadelphia Pa., Vol. 14, No. 8 (Apr. 17, 2000), pp. 25-28).


[0133] Monoclonal Antibodies


[0134] The term “monoclonal antibody” (MAb) or “monoclonal antibody composition”, as used herein, refers to a population of antibody molecules that contain only one molecular species of antibody molecule consisting of a unique light chain gene product and a unique heavy chain gene product. In particular, the complementarity determining regions (CDRs) of the monoclonal antibody are identical in all the molecules of the population. MAbs thus contain an antigen binding site capable of immunoreacting with a particular epitope of the antigen characterized by a unique binding affinity for it.


[0135] Monoclonal antibodies can be prepared using hybridoma methods, such as those described by Kohler and Milstein, Nature, 256:495 (1975). In a hybridoma method, a mouse, hamster, or other appropriate host animal, is typically immunized with an immunizing agent to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the immunizing agent. Alternatively, the lymphocytes can be immunized in vitro.


[0136] The immunizing agent will typically include the protein antigen, a fragment thereof or a fusion protein thereof. Generally, either peripheral blood lymphocytes are used if cells of human origin are desired, or spleen cells or lymph node cells are used if non-human mammalian sources are desired. The lymphocytes are then fused with an immortalized cell line using a suitable fusing agent, such as polyethylene glycol, to form a hybridoma cell [Goding, Monoclonal Antibodies: Principles and Practice, Academic Press, (1986) pp. 59-103]. Immortalized cell lines are usually transformed mammalian cells, particularly myeloma cells of rodent, bovine and human origin. Usually, rat or mouse myeloma cell lines are employed. The hybridoma cells can be cultured in a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, immortalized cells. For example, if the parental cells lack the enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT or HPRT), the culture medium for the hybridomas typically will include hypoxanthine, aminopterin, and thymidine (“HAT medium”), which substances prevent the growth of HGPRT-deficient cells. Preferred immortalized cell lines are those that fuse efficiently, support stable high level expression of antibody by the selected antibody-producing cells, and are sensitive to a medium such as HAT medium. More preferred immortalized cell lines are murine myeloma lines, which can be obtained, for instance, from the Salk Institute Cell Distribution Center, San Diego, Calif. and the American Type Culture Collection, Manassas, Va. Human myeloma and mouse-human heteromyeloma cell lines also have been described for the production of human monoclonal antibodies [Kozbor, J. Immunol., 133:3001 (1984); Brodeur et al., Monoclonal Antibody Production Techniques and Applications, Marcel Dekker, Inc., New York, (1987) pp. 51-63].


[0137] The culture medium in which the hybridoma cells are cultured can then be assayed for the presence of monoclonal antibodies directed against the antigen. Preferably, the binding specificity of monoclonal antibodies produced by the hybridoma cells is determined by immunoprecipitation or by an in vitro binding assay, such as radioimmunoassay (RIA) or enzyme-linked immunoabsorbent assay (ELISA). Such techniques and assays are known in the art. The binding affinity of the monoclonal antibody can, for example, be determined by the Scatchard analysis of Munson and Pollard, Anal. Biochem., 107:220 (1980). It is an objective, especially important in therapeutic applications of monoclonal antibodies, to identify antibodies having a high degree of specificity and a high binding affinity for the target antigen.


[0138] After the desired hybridoma cells are identified, the clones can be subcloned by limiting dilution procedures and grown by standard methods (Goding, 1986). Suitable culture media for this purpose include, for example, Dulbecco's Modified Eagle's Medium and RPMI-1640 medium. Alternatively, the hybridoma cells can be grown in vivo as ascites in a mammal.


[0139] The monoclonal antibodies secreted by the subclones can be isolated or purified from the culture medium or ascites fluid by conventional immunoglobulin purification procedures such as, for example, protein A-Sepharose, hydroxylapatite chromatography, gel electrophoresis, dialysis, or affinity chromatography.


[0140] The monoclonal antibodies can also be made by recombinant DNA methods, such as those described in U.S. Pat. No. 4,816,567. DNA encoding the monoclonal antibodies of the invention can be readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of murine antibodies). The hybridoma cells of the invention serve as a preferred source of such DNA. Once isolated, the DNA can be placed into expression vectors, which are then transfected into host cells such as simian COS cells, Chinese hamster ovary (CHO) cells, or myeloma cells that do not otherwise produce immunoglobulin protein, to obtain the synthesis of monoclonal antibodies in the recombinant host cells. The DNA also can be modified, for example, by substituting the coding sequence for human heavy and light chain constant domains in place of the homologous murine sequences (U.S. Pat. No. 4,816,567; Morrison, Nature 368, 812-13 (1994)) or by covalently joining to the immunoglobulin coding sequence all or part of the coding sequence for a non-immunoglobulin polypeptide. Such a non-immunoglobulin polypeptide can be substituted for the constant domains of an antibody of the invention, or can be substituted for the variable domains of one antigen-combining site of an antibody of the invention to create a chimeric bivalent antibody.


[0141] Humanized Antibodies


[0142] The antibodies directed against the protein antigens of the invention can further comprise humanized antibodies or human antibodies. These antibodies are suitable for administration to humans without engendering an immune response by the human against the administered immunoglobulin. Humanized forms of antibodies are chimeric immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab′, F(ab′)2 or other antigen-binding subsequences of antibodies) that are principally comprised of the sequence of a human immunoglobulin, and contain minimal sequence derived from a non-human immunoglobulin. Humanization can be performed following the method of Winter and co-workers (Jones et al., Nature, 321:522-525 (1986); Riechmann et al., Nature, 332:323-327 (1988); Verhoeyen et al., Science, 239:1534-1536 (1988)), by substituting rodent CDRs or CDR sequences for the corresponding sequences of a human antibody. (See also U.S. Pat. No. 5,225,539.) In some instances, Fv framework residues of the human immunoglobulin are replaced by corresponding non-human residues. Humanized antibodies can also comprise residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the framework regions are those of a human immunoglobulin consensus sequence. The humanized antibody optimally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin (Jones et al., 1986; Riechmann et al., 1988; and Presta, Curr. Op. Struct. Biol., 2:593-596 (1992)).


[0143] Human Antibodies


[0144] Fully human antibodies essentially relate to antibody molecules in which the entire sequence of both the light chain and the heavy chain, including the CDRs, arise from human genes. Such antibodies are termed “human antibodies”, or “fully human antibodies” herein. Human monoclonal antibodies can be prepared by the trioma technique; the human B-cell hybridoma technique (see Kozbor, et al., 1983 Immunol Today 4: 72) and the EBV hybridoma technique to produce human monoclonal antibodies (see Cole, et al., 1985 In: MONOCLONAL ANTIBODIES AND CANCER THERAPY, Alan R. Liss, Inc., pp. 77-96). Human monoclonal antibodies may be utilized in the practice of the present invention and may be produced by using human hybridomas (see Cote, et al., 1983. Proc Natl Acad Sci USA 80: 2026-2030) or by transforming human B-cells with Epstein Barr Virus in vitro (see Cole, et al., 1985 In: MONOCLONAL ANTIBODIES AND CANCER THERAPY, Alan R. Liss, Inc., pp. 77-96).


[0145] In addition, human antibodies can also be produced using additional techniques, including phage display libraries (Hoogenboom and Winter, J. Mol. Biol., 227:381 (1991); Marks et al., J. Mol. Biol., 222:581 (1991)). Similarly, human antibodies can be made by introducing human immunoglobulin loci into transgenic animals, e.g., mice in which the endogenous immunoglobulin genes have been partially or completely inactivated. Upon challenge, human antibody production is observed, which closely resembles that seen in humans in all respects, including gene rearrangement, assembly, and antibody repertoire. This approach is described, for example, in U.S. Pat. Nos. 5,545,807; 5,545,806; 5,569,825; 5,625,126; 5,633,425; 5,661,016, and in Marks et al. (Bio/Technology 10, 779-783 (1992)); Lonberg et al. Nature 368 856-859 (1994)); Morrison (Nature 368, 812-13 (1994)); Fishwild et al, (Nature Biotechnology 1, 845-51 (1996)); Neuberger (Nature Biotechnology 14, 826 (1996)); and Lonberg and Huszar (Intern. Rev. Immunol. 13 65-93 (1995)).


[0146] Human antibodies may additionally be produced using transgenic nonhuman animals which are modified so as to produce fully human antibodies rather than the animal's endogenous antibodies in response to challenge by an antigen. (See PCT publication WO94/02602). The endogenous genes encoding the heavy and light immunoglobulin chains in the nonhuman host have been incapacitated, and active loci encoding human heavy and light chain immunoglobulins are inserted into the host's genome. The human genes are incorporated, for example, using yeast artificial chromosomes containing the requisite human DNA segments. An animal which provides all the desired modifications is then obtained as progeny by crossbreeding intermediate transgenic animals containing fewer than the full complement of the modifications. The preferred embodiment of such a nonhuman animal is a mouse, and is termed the Xenomouse™ as disclosed in PCT publications WO 96/33735 and WO 96/34096. This animal produces B cells which secrete fully human immunoglobulins. The antibodies can be obtained directly from the animal after immunization with an immunogen of interest, as, for example, a preparation of a polyclonal antibody, or alternatively from immortalized B cells derived from the animal, such as hybridomas producing monoclonal antibodies. Additionally, the genes encoding the immunoglobulins with human variable regions can be recovered and expressed to obtain the antibodies directly, or can be further modified to obtain analogs of antibodies such as, for example, single chain Fv molecules.


[0147] An example of a method of producing a nonhuman host, exemplified as a mouse, lacking expression of an endogenous immunoglobulin heavy chain is disclosed in U.S. Pat. No. 5,939,598. It can be obtained by a method including deleting the J segment genes from at least one endogenous heavy chain locus in an embryonic stem cell to prevent rearrangement of the locus and to prevent formation of a transcript of a rearranged immunoglobulin heavy chain locus, the deletion being effected by a targeting vector containing a gene encoding a selectable marker; and producing from the embryonic stem cell a transgenic mouse whose somatic and germ cells contain the gene encoding the selectable marker.


[0148] A method for producing an antibody of interest, such as a human antibody, is disclosed in U.S. Pat. No. 5,916,771. It includes introducing an expression vector that contains a nucleotide sequence encoding a heavy chain into one mammalian host cell in culture, introducing an expression vector containing a nucleotide sequence encoding a light chain into another mammalian host cell, and fusing the two cells to form a hybrid cell. The hybrid cell expresses an antibody containing the heavy chain and the light chain.


[0149] In a further improvement on this procedure, a method for identifying a clinically relevant epitope on an immunogen, and a correlative method for selecting an antibody that binds immunospecifically to the relevant epitope with high affinity, are disclosed in PCT publication WO 99/53049.


[0150] Fab Fragments and Single Chain Antibodies


[0151] According to the invention, techniques can be adapted for the production of single-chain antibodies specific to an antigenic protein of the invention (see e.g., U.S. Pat. No. 4,946,778). In addition, methods can be adapted for the construction of Fab expression libraries (see e.g., Huse, et al., 1989 Science 246: 1275-1281) to allow rapid and effective identification of monoclonal Fab fragments with the desired specificity for a protein or derivatives, fragments, analogs or homologs thereof. Antibody fragments that contain the idiotypes to a protein antigen may be produced by techniques known in the art including, but not limited to: (i) an F(ab′)2 fragment produced by pepsin digestion of an antibody molecule; (ii) an Fab fragment generated by reducing the disulfide bridges of an F(ab′)2 fragment; (iii) an Fab fragment generated by the treatment of the antibody molecule with papain and a reducing agent and (iv) Fv fragments.


[0152] Bispecific Antibodies


[0153] Bispecific antibodies are monoclonal, preferably human or humanized, antibodies that have binding specificities for at least two different antigens. In the present case, one of the binding specificities is for an antigenic protein of the invention. The second binding target is any other antigen, and advantageously is a cell-surface protein or receptor or receptor subunit.


[0154] Methods for making bispecific antibodies are known in the art. Traditionally, the recombinant production of bispecific antibodies is based on the co-expression of two immunoglobulin heavy-chain/light-chain pairs, where the two heavy chains have different specificities (Milstein and Cuello, Nature, 305:537-539 (1983)). Because of the random assortment of immunoglobulin heavy and light chains, these hybridomas (quadromas) produce a potential mixture of ten different antibody molecules, of which only one has the correct bispecific structure. The purification of the correct molecule is usually accomplished by affinity chromatography steps. Similar procedures are disclosed in WO 93/08829, published May 13, 1993, and in Traunecker et al., EMBO J. 10:3655-3659 (1991).


[0155] Antibody variable domains with the desired binding specificities (antibody-antigen combining sites) can be fused to immunoglobulin constant domain sequences. The fusion preferably is with an immunoglobulin heavy-chain constant domain, comprising at least part of the hinge, CH2, and CH3 regions. It is preferred to have the first heavy-chain constant region (CH1) containing the site necessary for light-chain binding present in at least one of the fusions. DNAs encoding the immunoglobulin heavy-chain fusions and, if desired, the immunoglobulin light chain, are inserted into separate expression vectors, and are co-transfected into a suitable host organism. For further details of generating bispecific antibodies see, for example, Suresh et al., Methods in Enzymology, 121:210 (1986).


[0156] According to another approach described in WO 96/27011, the interface between a pair of antibody molecules can be engineered to maximize the percentage of heterodimers which are recovered from recombinant cell culture. The preferred interface comprises at least a part of the CH3 region of an antibody constant domain. In this method, one or more small amino acid side chains from the interface of the first antibody molecule are replaced with larger side chains (e.g. tyrosine or tryptophan). Compensatory “cavities” of identical or similar size to the large side chain(s) are created on the interface of the second antibody molecule by replacing large amino acid side chains with smaller ones (e.g. alanine or threonine). This provides a mechanism for increasing the yield of the heterodimer over other unwanted end-products such as homodimers.


[0157] Bispecific antibodies can be prepared as full length antibodies or antibody fragments (e.g. F(ab′)2 bispecific antibodies). Techniques for generating bispecific antibodies from antibody fragments have been described in the literature. For example, bispecific antibodies can be prepared using chemical linkage. Brennan et al., Science 229:81 (1985) describe a procedure wherein intact antibodies are proteolytically cleaved to generate F(ab′)2 fragments. These fragments are reduced in the presence of the dithiol complexing agent sodium arsenite to stabilize vicinal dithiols and prevent intermolecular disulfide formation. The Fab′ fragments generated are then converted to thionitrobenzoate (TNB) derivatives. One of the Fab′-TNB derivatives is then reconverted to the Fab′-thiol by reduction with mercaptoethylamine and is mixed with an equimolar amount of the other Fab′-TNB derivative to form the bispecific antibody. The bispecific antibodies produced can be used as agents for the selective immobilization of enzymes.


[0158] Additionally, Fab′ fragments can be directly recovered from E. coli and chemically coupled to form bispecific antibodies. Shalaby et al., J. Exp. Med. 175:217-225 (1992) describe the production of a fully humanized bispecific antibody F(ab′)2 molecule. Each Fab′ fragment was separately secreted from E. coli and subjected to directed chemical coupling in vitro to form the bispecific antibody. The bispecific antibody thus formed was able to bind to cells overexpressing the ErbB2 receptor and normal human T cells, as well as trigger the lytic activity of human cytotoxic lymphocytes against human breast tumor targets.


[0159] Various techniques for making and isolating bispecific antibody fragments directly from recombinant cell culture have also been described. For example, bispecific antibodies have been produced using leucine zippers. Kostelny et al., J. Immunol. 148(5):1547-1553 (1992). The leucine zipper peptides from the Fos and Jun proteins were linked to the Fab′ portions of two different antibodies by gene fusion. The antibody homodimers were reduced at the hinge region to form monomers and then re-oxidized to form the antibody heterodimers. This method can also be utilized for the production of antibody homodimers. The “diabody” technology described by Hollinger et al., Proc. Natl. Acad. Sci. USA 90:6444-6448 (1993) has provided an alternative mechanism for making bispecific antibody fragments. The fragments comprise a heavy-chain variable domain (VH) connected to a light-chain variable domain (VL) by a linker which is too short to allow pairing between the two domains on the same chain. Accordingly, the VH and VL domains of one fragment are forced to pair with the complementary VL and VH domains of another fragment, thereby forming two antigen-binding sites. Another strategy for making bispecific antibody fragments by the use of single-chain Fv (sFv) dimers has also been reported. See, Gruber et al., J. Immunol. 152:5368 (1994).


[0160] Antibodies with more than two valencies are contemplated. For example, trispecific antibodies can be prepared. Tutt et al., J. Immunol. 147:60 (1991).


[0161] Exemplary bispecific antibodies can bind to two different epitopes, at least one of which originates in the protein antigen of the invention. Alternatively, an anti-antigenic arm of an immunoglobulin molecule can be combined with an arm which binds to a triggering molecule on a leukocyte such as a T-cell receptor molecule (e.g. CD2, CD3, CD28, or B7), or Fc receptors for IgG (FcγR), such as FcγRI (CD64), FcγRII (CD32) and FcγRIII (CD16) so as to focus cellular defense mechanisms to the cell expressing the particular antigen. Bispecific antibodies can also be used to direct cytotoxic agents to cells which express a particular antigen. These antibodies possess an antigen-binding arm and an arm which binds a cytotoxic agent or a radionuclide chelator, such as EOTUBE, DPTA, DOTA, or TETA. Another bispecific antibody of interest binds the protein antigen described herein and further binds tissue factor (TF).


[0162] Heteroconjugate Antibodies


[0163] Heteroconjugate antibodies are also within the scope of the present invention. Heteroconjugate antibodies are composed of two covalently joined antibodies. Such antibodies have, for example, been proposed to target immune system cells to unwanted cells (U.S. Pat. No. 4,676,980), and for treatment of HIV infection (WO 91/00360; WO 92/200373; EP 03089). It is contemplated that the antibodies can be prepared in vitro using known methods in synthetic protein chemistry, including those involving crosslinking agents. For example, immunotoxins can be constructed using a disulfide exchange reaction or by forming a thioether bond. Examples of suitable reagents for this purpose include iminothiolate and methyl-4-mercaptobutyrimidate and those disclosed, for example, in U.S. Pat. No. 4,676,980.


[0164] Effector Function Engineering


[0165] It can be desirable to modify the antibody of the invention with respect to effector function, so as to enhance, e.g., the effectiveness of the antibody in treating cancer. For example, cysteine residue(s) can be introduced into the Fc region, thereby allowing interchain disulfide bond formation in this region. The homodimeric antibody thus generated can have improved internalization capability and/or increased complement-mediated cell killing and antibody-dependent cellular cytotoxicity (ADCC). See Caron et al., J. Exp Med., 176: 1191-1195 (1992) and Shopes, J. Immunol., 148: 2918-2922 (1992). Homodimeric antibodies with enhanced anti-tumor activity can also be prepared using heterobifunctional cross-linkers as described in Wolff et al. Cancer Research, 53: 2560-2565 (1993). Alternatively, an antibody can be engineered that has dual Fc regions and can thereby have enhanced complement lysis and ADCC capabilities. See Stevenson et al., Anti-Cancer Drug Design, 3: 219-230 (1989).


[0166] Immunoconjugates


[0167] The invention also pertains to immunoconjugates comprising an antibody conjugated to a cytotoxic agent such as a chemotherapeutic agent, toxin (e.g., an enzymatically active toxin of bacterial, fungal, plant, or animal origin, or fragments thereof), or a radioactive isotope (i.e., a radioconjugate).


[0168] Chemotherapeutic agents useful in the generation of such immunoconjugates have been described above. Enzymatically active toxins and fragments thereof that can be used include diphtheria A chain, nonbinding active fragments of diphtheria toxin, exotoxin A chain (from Pseudomonas aeruginosa), ricin A chain, abrin A chain, modeccin A chain, alpha-sarcin, Aleurites fordii proteins, dianthin proteins, Phytolaca americana proteins (PAPI, PAPII, and PAP-S), momordica charantia inhibitor, curcin, crotin, sapaonaria officinalis inhibitor, gelonin, mitogellin, restrictocin, phenomycin, enomycin, and the tricothecenes. A variety of radionuclides are available for the production of radioconjugated antibodies. Examples include 212Bi, 131i, 131In, 90Y, and 18Re.


[0169] Conjugates of the antibody and cytotoxic agent are made using a variety of bifunctional protein-coupling agents such as N-succinimidyl-3-(2-pyridyldithiol) propionate (SPDP), iminothiolane (IT), bifunctional derivatives of imidoesters (such as dimethyl adipimidate HCL), active esters (such as disuccinimidyl suberate), aldehydes (such as glutareldehyde), bis-azido compounds (such as bis (p-azidobenzoyl) hexanediamine), bis-diazonium derivatives (such as bis-(p-diazoniumbenzoyl)-ethylenediamine), diisocyanates (such as tolyene 2,6-diisocyanate), and bis-active fluorine compounds (such as 1,5-difluoro-2,4-dinitrobenzene). For example, a ricin immunotoxin can be prepared as described in Vitetta et al., Science, 238: 1098 (1987). Carbon-14-labeled 1-isothiocyanatobenzyl-3-methyldiethylene triaminepentaacetic acid (MX-DTPA) is an exemplary chelating agent for conjugation of radionucleotide to the antibody. See WO94/11026.


[0170] In another embodiment, the antibody can be conjugated to a “receptor” (such streptavidin) for utilization in tumor pretargeting wherein the antibody-receptor conjugate is administered to the patient, followed by removal of unbound conjugate from the circulation using a clearing agent and then administration of a “ligand” (e.g., avidin) that is in turn conjugated to a cytotoxic agent.


[0171] Immunoliposomes


[0172] The antibodies disclosed herein can also be formulated as immunoliposomes. Liposomes containing the antibody are prepared by methods known in the art, such as described in Epstein et al., Proc. Natl. Acad. Sci. USA, 82: 3688 (1985); Hwang et al., Proc. Natl. Acad. Sci. USA, 77: 4030 (1980); and U.S. Pat. Nos. 4,485,045 and 4,544,545. Liposomes with enhanced circulation time are disclosed in U.S. Pat. No. 5,013,556.


[0173] Particularly useful liposomes can be generated by the reverse-phase evaporation method with a lipid composition comprising phosphatidylcholine, cholesterol, and PEG-derivatized phosphatidylethanolamine (PEG-PE). Liposomes are extruded through filters of defined pore size to yield liposomes with the desired diameter. Fab′ fragments of the antibody of the present invention can be conjugated to the liposomes as described in Martin et al., J. Biol. Chem., 257: 286-288 (1982) via a disulfide-interchange reaction. A chemotherapeutic agent (such as Doxorubicin) is optionally contained within the liposome. See Gabizon et al., J. National Cancer Inst., 81(19): 1484 (1989).


[0174] Diagnostic Applications of Antibodies Directed Against the Proteins of the Invention


[0175] Antibodies directed against a protein of the invention may be used in methods known within the art relating to the localization and/or quantitation of the protein (e.g., for use in measuring levels of the protein within appropriate physiological samples, for use in diagnostic methods, for use in imaging the protein, and the like). In a given embodiment, antibodies against the proteins, or derivatives, fragments, analogs or homologs thereof, that contain the antigen binding domain, are utilized as pharmacologically-active compounds (see below).


[0176] An antibody specific for a protein of the invention can be used to isolate the protein by standard techniques, such as immunoaffinity chromatography or immunoprecipitation. Such an antibody can facilitate the purification of the natural protein antigen from cells and of recombinantly produced antigen expressed in host cells. Moreover, such an antibody can be used to detect the antigenic protein (e.g., in a cellular lysate or cell supernatant) in order to evaluate the abundance and pattern of expression of the antigenic protein. Antibodies directed against the protein can be used diagnostically to monitor protein levels in tissue as part of a clinical testing procedure, e.g., to, for example, determine the efficacy of a given treatment regimen. Detection can be facilitated by coupling (i.e., physically linking) the antibody to a detectable substance. Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, β-galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include streptavidin/biotin and avidin/biotin; examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin, and examples of suitable radioactive material include 125I, 131I, 35S or 3H.


[0177] Antibody Therapeutics


[0178] Antibodies of the invention, including polyclonal, monoclonal, humanized and fully human antibodies, may used as therapeutic agents. Such agents will generally be employed to treat or prevent a disease or pathology in a subject. An antibody preparation, preferably one having high specificity and high affinity for its target antigen, is administered to the subject and will generally have an effect due to its binding with the target. Such an effect may be one of two kinds, depending on the specific nature of the interaction between the given antibody molecule and the target antigen in question. In the first instance, administration of the antibody may abrogate or inhibit the binding of the target with an endogenous ligand to which it naturally binds. In this case, the antibody binds to the target and masks a binding site of the naturally occurring ligand, wherein the ligand serves as an effector molecule. Thus the receptor mediates a signal transduction pathway for which ligand is responsible.


[0179] Alternatively, the effect may be one in which the antibody elicits a physiological result by virtue of binding to an effector binding site on the target molecule. In this case the target, a receptor having an endogenous ligand which may be absent or defective in the disease or pathology, binds the antibody as a surrogate effector ligand, initiating a receptor-based signal transduction event by the receptor.


[0180] A therapeutically effective amount of an antibody of the invention relates generally to the amount needed to achieve a therapeutic objective. As noted above, this may be a binding interaction between the antibody and its target antigen that, in certain cases, interferes with the functioning of the target, and in other cases, promotes a physiological response. The amount required to be administered will furthermore depend on the binding affinity of the antibody for its specific antigen, and will also depend on the rate at which an administered antibody is depleted from the free volume other subject to which it is administered. Common ranges for therapeutically effective dosing of an antibody or antibody fragment of the invention may be, by way of nonlimiting example, from about 0.1 mg/kg body weight to about 50 mg/kg body weight. Common dosing frequencies may range, for example, from twice daily to once a week.


[0181] Pharmaceutical Compositions of Antibodies


[0182] Antibodies specifically binding a protein of the invention, as well as other molecules identified by the screening assays disclosed herein, can be administered for the treatment of various disorders in the form of pharmaceutical compositions. Principles and considerations involved in preparing such compositions, as well as guidance in the choice of components are provided, for example, in Remington: The Science And Practice Of Pharmacy 19th ed. (Alfonso R. Gennaro, et al., editors) Mack Pub. Co., Easton, Pa.: 1995; Drug Absorption Enhancement: Concepts, Possibilities, Limitations, And Trends, Harwood Academic Publishers, Langhorne, Pa., 1994; and Peptide And Protein Drug Delivery (Advances In Parenteral Sciences, Vol. 4), 1991, M. Dekker, New York.


[0183] If the antigenic protein is intracellular and whole antibodies are used as inhibitors, internalizing antibodies are preferred. However, liposomes can also be used to deliver the antibody, or an antibody fragment, into cells. Where antibody fragments are used, the smallest inhibitory fragment that specifically binds to the binding domain of the target protein is preferred. For example, based upon the variable-region sequences of an antibody, peptide molecules can be designed that retain the ability to bind the target protein sequence. Such peptides can be synthesized chemically and/or produced by recombinant DNA technology. See, e.g., Marasco et al., Proc. Natl. Acad. Sci. USA, 90: 7889-7893 (1993). The formulation herein can also contain more than one active compound as necessary for the particular indication being treated, preferably those with complementary activities that do not adversely affect each other. Alternatively, or in addition, the composition can comprise an agent that enhances its function, such as, for example, a cytotoxic agent, cytokine, chemotherapeutic agent, or growth-inhibitory agent. Such molecules are suitably present in combination in amounts that are effective for the purpose intended.


[0184] The active ingredients can also be entrapped in microcapsules prepared, for example, by coacervation techniques or by interfacial polymerization, for example, hydroxymethylcellulose or gelatin-microcapsules and poly-(methylmethacrylate) microcapsules, respectively, in colloidal drug delivery systems (for example, liposomes, albumin microspheres, microemulsions, nano-particles, and nanocapsules) or in macroemulsions.


[0185] The formulations to be used for in vivo administration must be sterile. This is readily accomplished by filtration through sterile filtration membranes.


[0186] Sustained-release preparations can be prepared. Suitable examples of sustained-release preparations include semipermeable matrices of solid hydrophobic polymers containing the antibody, which matrices are in the form of shaped articles, e.g., films, or microcapsules. Examples of sustained-release matrices include polyesters, hydrogels (for example, poly(2-hydroxyethyl-methacrylate), or poly(vinylalcohol)), polylactides (U.S. Pat. No. 3,773,919), copolymers of L-glutamic acid and γ ethyl-L-glutamate, non-degradable ethylene-vinyl acetate, degradable lactic acid-glycolic acid copolymers such as the LUPRON DEPOT™ (injectable microspheres composed of lactic acid-glycolic acid copolymer and leuprolide acetate), and poly-D-(−)-3-hydroxybutyric acid. While polymers such as ethylene-vinyl acetate and lactic acid-glycolic acid enable release of molecules for over 100 days, certain hydrogels release proteins for shorter time periods.


[0187] ELISA Assay


[0188] An agent for detecting an analyte protein is an antibody capable of binding to an analyte protein, preferably an antibody with a detectable label. Antibodies can be polyclonal, or more preferably, monoclonal. An intact antibody, or a fragment thereof (e.g., Fab or F(ab)2) can be used. The term “labeled”, with regard to the probe or antibody, is intended to encompass direct labeling of the probe or antibody by coupling (i.e., physically linking) a detectable substance to the probe or antibody, as well as indirect labeling of the probe or antibody by reactivity with another reagent that is directly labeled. Examples of indirect labeling include detection of a primary antibody using a fluorescently-labeled secondary antibody and end-labeling of a DNA probe with biotin such that it can be detected with fluorescently-labeled streptavidin. The term “biological sample” is intended to include tissues, cells and biological fluids isolated from a subject, as well as tissues, cells and fluids present within a subject. Included within the usage of the term “biological sample”, therefore, is blood and a fraction or component of blood including blood serum, blood plasma, or lymph. That is, the detection method of the invention can be used to detect an analyte mRNA, protein, or genomic DNA in a biological sample in vitro as well as in vivo. For example, in vitro techniques for detection of an analyte mRNA include Northern hybridizations and in situ hybridizations. In vitro techniques for detection of an analyte protein include enzyme linked immunosorbent assays (ELISAs), Western blots, immunoprecipitations, and immunofluorescence. In vitro techniques for detection of an analyte genomic DNA include Southern hybridizations. Procedures for conducting immunoassays are described, for example in “ELISA: Theory and Practice: Methods in Molecular Biology”, Vol. 42, J. R. Crowther (Ed.) Human Press, Totowa, N.J., 1995; “Immunoassay”, E. Diamandis and T. Christopoulus, Academic Press, Inc., San Diego, Calif., 1996; and “Practice and Thory of Enzyme Immunoassays”, P. Tijssen, Elsevier Science Publishers, Amsterdam, 1985. Furthermore, in vivo techniques for detection of an analyte protein include introducing into a subject a labeled anti-an analyte protein antibody. For example, the antibody can be labeled with a radioactive marker whose presence and location in a subject can be detected by standard imaging techniques.


[0189] NOVX Recombinant Expression Vectors and Host Cells


[0190] Another aspect of the invention pertains to vectors, preferably expression vectors, containing a nucleic acid encoding an NOVX protein, or derivatives, fragments, analogs or homologs thereof. As used herein, the term “vector” refers to a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked. One type of vector is a “plasmid”, which refers to a circular double stranded DNA loop into which additional DNA segments can be ligated. Another type of vector is a viral vector, wherein additional DNA segments can be ligated into the viral genome. Certain vectors are capable of autonomous replication in a host cell into which they are introduced (e.g., bacterial vectors having a bacterial origin of replication and episomal mammalian vectors). Other vectors (e.g., non-episomal mammalian vectors) are integrated into the genome of a host cell upon introduction into the host cell, and thereby are replicated along with the host genome. Moreover, certain vectors are capable of directing the expression of genes to which they are operatively-linked. Such vectors are referred to herein as “expression vectors”. In general, expression vectors of utility in recombinant DNA techniques are often in the form of plasmids. In the present specification, “plasmid” and “vector” can be used interchangeably as the plasmid is the most commonly used form of vector. However, the invention is intended to include such other forms of expression vectors, such as viral vectors (e.g., replication defective retroviruses, adenoviruses and adeno-associated viruses), which serve equivalent functions.


[0191] The recombinant expression vectors of the invention comprise a nucleic acid of the invention in a form suitable for expression of the nucleic acid in a host cell, which means that the recombinant expression vectors include one or more regulatory sequences, selected on the basis of the host cells to be used for expression, that is operatively-linked to the nucleic acid sequence to be expressed. Within a recombinant expression vector, “operably-linked” is intended to mean that the nucleotide sequence of interest is linked to the regulatory sequence(s) in a manner that allows for expression of the nucleotide sequence (e.g., in an in vitro transcription/translation system or in a host cell when the vector is introduced into the host cell).


[0192] The term “regulatory sequence” is intended to includes promoters, enhancers and other expression control elements (e.g., polyadenylation signals). Such regulatory sequences are described, for example, in Goeddel, GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990). Regulatory sequences include those that direct constitutive expression of a nucleotide sequence in many types of host cell and those that direct expression of the nucleotide sequence only in certain host cells (e.g., tissue-specific regulatory sequences). It will be appreciated by those skilled in the art that the design of the expression vector can depend on such factors as the choice of the host cell to be transformed, the level of expression of protein desired, etc. The expression vectors of the invention can be introduced into host cells to thereby produce proteins or peptides, including fusion proteins or peptides, encoded by nucleic acids as described herein (e.g., NOVX proteins, mutant forms of NOVX proteins, fusion proteins, etc.).


[0193] The recombinant expression vectors of the invention can be designed for expression of NOVX proteins in prokaryotic or eukaryotic cells. For example, NOVX proteins can be expressed in bacterial cells such as Escherichia coli, insect cells (using baculovirus expression vectors) yeast cells or mammalian cells. Suitable host cells are discussed further in Goeddel, GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990). Alternatively, the recombinant expression vector can be transcribed and translated in vitro, for example using T7 promoter regulatory sequences and T7 polymerase.


[0194] Expression of proteins in prokaryotes is most often carried out in Escherichia coli with vectors containing constitutive or inducible promoters directing the expression of either fusion or non-fusion proteins. Fusion vectors add a number of amino acids to a protein encoded therein, usually to the amino terminus of the recombinant protein. Such fusion vectors typically serve three purposes: (i) to increase expression of recombinant protein; (ii) to increase the solubility of the recombinant protein; and (iii) to aid in the purification of the recombinant protein by acting as a ligand in affinity purification. Often, in fusion expression vectors, a proteolytic cleavage site is introduced at the junction of the fusion moiety and the recombinant protein to enable separation of the recombinant protein from the fusion moiety subsequent to purification of the fusion protein. Such enzymes, and their cognate recognition sequences, include Factor Xa, thrombin and enterokinase. Typical fusion expression vectors include pGEX (Pharmacia Biotech Inc; Smith and Johnson, 1988. Gene 67: 31-40), pMAL (New England Biolabs, Beverly, Mass.) and pRIT5 (Pharmacia, Piscataway, N.J.) that fuse glutathione S-transferase (GST), maltose E binding protein, or protein A, respectively, to the target recombinant protein. Examples of suitable inducible non-fusion E. coli expression vectors include pTrc (Amrann et al., (1988) Gene 69:301-315) and pET 11d (Studier et al., GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990) 60-89).


[0195] One strategy to maximize recombinant protein expression in E. coli is to express the protein in a host bacteria with an impaired capacity to proteolytically cleave the recombinant protein. See, e.g., Gottesman, GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990) 119-128. Another strategy is to alter the nucleic acid sequence of the nucleic acid to be inserted into an expression vector so that the individual codons for each amino acid are those preferentially utilized in E. coli (see, e.g., Wada, et al., 1992. Nucl. Acids Res. 20: 2111-2118). Such alteration of nucleic acid sequences of the invention can be carried out by standard DNA synthesis techniques.


[0196] In another embodiment, the NOVX expression vector is a yeast expression vector. Examples of vectors for expression in yeast Saccharomyces cerivisae include pYepSecI (Baldari, et al., 1987. EMBO J. 6: 229-234), pMFa (Kurjan and Herskowitz, 1982. Cell 30: 933-943), pJRY88 (Schultz et al., 1987. Gene 54: 113-123), pYES2 (Invitrogen Corporation, San Diego, Calif.), and picZ (InVitrogen Corp, San Diego, Calif.). Alternatively, NOVX can be expressed in insect cells using baculovirus expression vectors. Baculovirus vectors available for expression of proteins in cultured insect cells (e.g., SF9 cells) include the pAc series (Smith, et al., 1983. Mol. Cell. Biol. 3: 2156-2165) and the pVL series (Lucklow and Summers, 1989. Virology 170: 31-39).


[0197] In yet another embodiment, a nucleic acid of the invention is expressed in mammalian cells using a mammalian expression vector. Examples of mammalian expression vectors include pCDM8 (Seed, 1987. Nature 329: 840) and pMT2PC (Kaufman, et al., 1987. EMBO J. 6: 187-195). When used in mammalian cells, the expression vector's control functions are often provided by viral regulatory elements. For example, commonly used promoters are derived from polyoma, adenovirus 2, cytomegalovirus, and simian virus 40. For other suitable expression systems for both prokaryotic and eukaryotic cells see, e.g., Chapters 16 and 17 of Sambrook, et al., MOLECULAR CLONING: A LABORATORY MANUAL. 2nd ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989.


[0198] In another embodiment, the recombinant mammalian expression vector is capable of directing expression of the nucleic acid preferentially in a particular cell type (e.g., tissue-specific regulatory elements are used to express the nucleic acid). Tissue-specific regulatory elements are known in the art. Non-limiting examples of suitable tissue-specific promoters include the albumin promoter (liver-specific; Pinkert, et al., 1987. Genes Dev. 1: 268-277), lymphoid-specific promoters (Calame and Eaton, 1988. Adv. Immunol. 43: 235-275), in particular promoters of T cell receptors (Winoto and Baltimore, 1989. EMBO J. 8: 729-733) and immunoglobulins (Banedji, et al., 1983. Cell 33: 729-740; Queen and Baltimore, 1983. Cell 33: 741-748), neuron-specific promoters (e.g., the neurofilament promoter; Byrne and Ruddle, 1989. Proc. Natl. Acad. Sci. USA 86: 5473-5477), pancreas-specific promoters (Edlund, et al., 1985. Science 230: 912-916), and mammary gland-specific promoters (e.g., milk whey promoter; U.S. Pat. No. 4,873,316 and European Application Publication No. 264,166). Developmentally-regulated promoters are also encompassed, e.g., the murine hox promoters (Kessel and Gruss, 1990. Science 249: 374-379) and the α-fetoprotein promoter (Campes and Tilghman, 1989. Genes Dev. 3: 537-546).


[0199] The invention further provides a recombinant expression vector comprising a DNA molecule of the invention cloned into the expression vector in an antisense orientation. That is, the DNA molecule is operatively-linked to a regulatory sequence in a manner that allows for expression (by transcription of the DNA molecule) of an RNA molecule that is antisense to NOVX mRNA. Regulatory sequences operatively linked to a nucleic acid cloned in the antisense orientation can be chosen that direct the continuous expression of the antisense RNA molecule in a variety of cell types, for instance viral promoters and/or enhancers, or regulatory sequences can be chosen that direct constitutive, tissue specific or cell type specific expression of antisense RNA. The antisense expression vector can be in the form of a recombinant plasmid, phagemid or attenuated virus in which antisense nucleic acids are produced under the control of a high efficiency regulatory region, the activity of which can be determined by the cell type into which the vector is introduced. For a discussion of the regulation of gene expression using antisense genes see, e.g., Weintraub, et al., “Antisense RNA as a molecular tool for genetic analysis,” Reviews-Trends in Genetics, Vol. 1(1) 1986.


[0200] Another aspect of the invention pertains to host cells into which a recombinant expression vector of the invention has been introduced. The terms “host cell” and “recombinant host cell” are used interchangeably herein. It is understood that such terms refer not only to the particular subject cell but also to the progeny or potential progeny of such a cell. Because certain modifications may occur in succeeding generations due to either mutation or environmental influences, such progeny may not, in fact, be identical to the parent cell, but are still included within the scope of the term as used herein A host cell can be any prokaryotic or eukaryotic cell. For example, NOVX protein can be expressed in bacterial cells such as E. coli, insect cells, yeast or mammalian cells (such as Chinese hamster ovary cells (CHO) or COS cells). Other suitable host cells are known to those skilled in the art.


[0201] Vector DNA can be introduced into prokaryotic or eukaryotic cells via conventional transformation or transfection techniques. As used herein, the terms “transformation” and “transfection” are intended to refer to a variety of art-recognized techniques for introducing foreign nucleic acid (e.g., DNA) into a host cell, including calcium phosphate or calcium chloride co-precipitation, DEAE-dextran-mediated transfection, lipofection, or electroporation. Suitable methods for transforming or transfecting host cells can be found in Sambrook, et al. (MOLECULAR CLONING: A LABORATORY MANUAL. 2nd ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989), and other laboratory manuals.


[0202] For stable transfection of mammalian cells, it is known that, depending upon the expression vector and transfection technique used, only a small fraction of cells may integrate the foreign DNA into their genome. In order to identify and select these integrants, a gene that encodes a selectable marker (e.g., resistance to antibiotics) is generally introduced into the host cells along with the gene of interest. Various selectable markers include those that confer resistance to drugs, such as G418, hygromycin and methotrexate. Nucleic acid encoding a selectable marker can be introduced into a host cell on the same vector as that encoding NOVX or can be introduced on a separate vector. Cells stably transfected with the introduced nucleic acid can be identified by drug selection (e.g., cells that have incorporated the selectable marker gene will survive, while the other cells die).


[0203] A host cell of the invention, such as a prokaryotic or eukaryotic host cell in culture, can be used to produce (i.e., express) NOVX protein. Accordingly, the invention further provides methods for producing NOVX protein using the host cells of the invention. In one embodiment, the method comprises culturing the host cell of invention (into which a recombinant expression vector encoding NOVX protein has been introduced) in a suitable medium such that NOVX protein is produced. In another embodiment, the method further comprises isolating NOVX protein from the medium or the host cell.


[0204] Transgenic NOVX Animals


[0205] The host cells of the invention can also be used to produce non-human transgenic animals. For example, in one embodiment, a host cell of the invention is a fertilized oocyte or an embryonic stem cell into which NOVX protein-coding sequences have been introduced. Such host cells can then be used to create non-human transgenic animals in which exogenous NOVX sequences have been introduced into their genome or homologous recombinant animals in which endogenous NOVX sequences have been altered. Such animals are useful for studying the function and/or activity of NOVX protein and for identifying and/or evaluating modulators of NOVX protein activity. As used herein, a “transgenic animal” is a non-human animal, preferably a mammal, more preferably a rodent such as a rat or mouse, in which one or more of the cells of the animal includes a transgene Other examples of transgenic animals include non-human primates, sheep, dogs, cows, goats, chickens, amphibians, etc. A transgene is exogenous DNA that is integrated into the genome of a cell from which a transgenic animal develops and that remains in the genome of the mature animal, thereby directing the expression of an encoded gene product in one or more cell types or tissues of the transgenic animal. As used herein, a “homologous recombinant animal” is a non-human animal, preferably a mammal, more preferably a mouse, in which an endogenous NOVX gene has been altered by homologous recombination between the endogenous gene and an exogenous DNA molecule introduced into a cell of the animal, e.g., an embryonic cell of the animal, prior to development of the animal.


[0206] A transgenic animal of the invention can be created by introducing NOVX-encoding nucleic acid into the male pronuclei of a fertilized oocyte (e.g., by microinjection, retroviral infection) and allowing the oocyte to develop in a pseudopregnant female foster animal. The human NOVX cDNA sequences SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178 can be introduced as a transgene into the genome of a non-human animal. Alternatively, a non-human homologue of the human NOVX gene, such as a mouse NOVX gene, can be isolated based on hybridization to the human NOVX cDNA (described further supra) and used as a transgene. Intronic sequences and polyadenylation signals can also be included in the transgene to increase the efficiency of expression of the transgene. A tissue-specific regulatory sequence(s) can be operably-linked to the NOVX transgene to direct expression of NOVX protein to particular cells. Methods for generating transgenic animals via embryo manipulation and microinjection, particularly animals such as mice, have become conventional in the art and are described, for example, in U.S. Pat. Nos. 4,736,866; 4,870,009; and 4,873,191; and Hogan, 1986. In: MANIPULATING THE MOUSE EMBRYO, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. Similar methods are used for production of other transgenic animals. A transgenic founder animal can be identified based upon the presence of the NOVX transgene in its genome and/or expression of NOVX mRNA in tissues or cells of the animals. A transgenic founder animal can then be used to breed additional animals carrying the transgene. Moreover, transgenic animals carrying a transgene-encoding NOVX protein can further be bred to other transgenic animals carrying other transgenes.


[0207] To create a homologous recombinant animal, a vector is prepared which contains at least a portion of an NOVX gene into which a deletion, addition or substitution has been introduced to thereby alter, e.g., functionally disrupt, the NOVX gene. The NOVX gene can be a human gene (e.g., the cDNA of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178), but more preferably, is a non-human homologue of a human NOVX gene. For example, a mouse homologue of human NOVX gene of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178 can be used to construct a homologous recombination vector suitable for altering an endogenous NOVX gene in the mouse genome. In one embodiment, the vector is designed such that, upon homologous recombination, the endogenous NOVX gene is functionally disrupted (i.e., no longer encodes a functional protein; also referred to as a “knock out” vector).


[0208] Alternatively, the vector can be designed such that, upon homologous recombination, the endogenous NOVX gene is mutated or otherwise altered but still encodes functional protein (e.g., the upstream regulatory region can be altered to thereby alter the expression of the endogenous NOVX protein). In the homologous recombination vector, the altered portion of the NOVX gene is flanked at its 5′- and 3′-termini by additional nucleic acid of the NOVX gene to allow for homologous recombination to occur between the exogenous NOVX gene carried by the vector and an endogenous NOVX gene in an embryonic stem cell. The additional flanking NOVX nucleic acid is of sufficient length for successful homologous recombination with the endogenous gene. Typically, several kilobases of flanking DNA (both at the 5′- and 3′-termini) are included in the vector. See, e.g., Thomas, et al., 1987. Cell 51: 503 for a description of homologous recombination vectors. The vector is ten introduced into an embryonic stem cell line (e.g., by electroporation) and cells in which the introduced NOVX gene has homologously-recombined with the endogenous NOVX gene are selected. See, e.g., Li, et al., 1992. Cell 69: 915.


[0209] The selected cells are then injected into a blastocyst of an animal (e.g., a mouse) to form aggregation chimeras. See, e.g., Bradley, 1987. In: TETRATOCARCINOMAS AND EMBRYONIC STEM CELLS: A PRACTICAL APPROACH, Robertson, ed. IRL, Oxford, pp. 113-152. A chimeric embryo can then be implanted into a suitable pseudopregnant female foster animal and the embryo brought to term. Progeny harboring the homologously-recombined DNA in their germ cells can be used to breed animals in which all cells of the animal contain the homologously-recombined DNA by germline transmission of the transgene. Methods for constructing homologous recombination vectors and homologous recombinant animals are described further in Bradley, 1991. Curr. Opin. Biotechnol. 2: 823-829; PCT International Publication Nos.: WO 90/11354; WO 91/01140; WO 92/0968; and WO 93/04169.


[0210] In another embodiment, transgenic non-humans animals can be produced that contain selected systems that allow for regulated expression of the transgene. One example of such a system is the cre/loxP recombinase system of bacteriophage P1. For a description of the cre/loxP recombinase system, See, e.g., Lakso, et al., 1992. Proc. Natl. Acad. Sci. USA 89: 6232-6236. Another example of a recombinase system is the FLP recombinase system of Saccharomyces cerevisiae. See, O'Gorman, et al., 1991. Science 251:1351-1355. If a cre/loxP recombinase system is used to regulate expression of the transgene, animals containing transgenes encoding both the Cre recombinase and a selected protein are required. Such animals can be provided through the construction of “double” transgenic animals, e.g., by mating two transgenic animals, one containing a transgene encoding a selected protein and the other containing a transgene encoding a recombinase.


[0211] Clones of the non-human transgenic animals described herein can also be produced according to the methods described in Wilmut, et al., 1997. Nature 385: 810-813. In brief, a cell (e.g., a somatic cell) from the transgenic animal can be isolated and induced to exit the growth cycle and enter G0 phase. The quiescent cell can then be fused, e.g., through the use of electrical pulses, to an enucleated oocyte from an animal of the same species from which the quiescent cell is isolated. The reconstructed oocyte is then cultured such that it develops to morula or blastocyte and then transferred to pseudopregnant female foster animal. The offspring borne of this female foster animal will be a clone of the animal from which the cell (e.g., the somatic cell) is isolated.


[0212] Pharmaceutical Compositions


[0213] The NOVX nucleic acid molecules, NOVX proteins, and anti-NOVX antibodies (also referred to herein as “active compounds”) of the invention, and derivatives, fragments, analogs and homologs thereof, can be incorporated into pharmaceutical compositions suitable for administration. Such compositions typically comprise the nucleic acid molecule, protein, or antibody and a pharmaceutically acceptable carrier. As used herein, “pharmaceutically acceptable carrier” is intended to include any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like, compatible with pharmaceutical administration. Suitable carriers are described in the most recent edition of Remington's Pharmaceutical Sciences, a standard reference text in the field, which is incorporated herein by reference. Preferred examples of such carriers or diluents include, but are not limited to, water, saline, finger's solutions, dextrose solution, and 5% human serum albumin. Liposomes and non-aqueous vehicles such as fixed oils may also be used. The use of such media and agents for pharmaceutically active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active compound, use thereof in the compositions is contemplated. Supplementary active compounds can also be incorporated into the compositions.


[0214] A pharmaceutical composition of the invention is formulated to be compatible with its intended route of administration. Examples of routes of administration include parenteral, e.g., intravenous, intradermal, subcutaneous, oral (e.g., inhalation), transdermal (i.e., topical), transmucosal, and rectal administration. Solutions or suspensions used for parenteral, intradermal, or subcutaneous application can include the following components: a sterile diluent such as water for injection, saline solution, fixed oils, polyethylene glycols, glycerine, propylene glycol or other synthetic solvents; antibacterial agents such as benzyl alcohol or methyl parabens; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as ethylenediaminetetraacetic acid (EDTA); buffers such as acetates, citrates or phosphates, and agents for the adjustment of tonicity such as sodium chloride or dextrose. The pH can be adjusted with acids or bases, such as hydrochloric acid or sodium hydroxide. The parenteral preparation can be enclosed in ampoules, disposable syringes or multiple dose vials made of glass or plastic.


[0215] Pharmaceutical compositions suitable for injectable use include sterile aqueous solutions (where water soluble) or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersion. For intravenous administration, suitable carriers include physiological saline, bacteriostatic water, Cremophor EL™ (BASF, Parsippany, N.J.) or phosphate buffered saline (PBS). In all cases, the composition must be sterile and should be fluid to the extent that easy syringeability exists. It must be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), and suitable mixtures thereof. The proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. Prevention of the action of microorganisms can be achieved by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, ascorbic acid, thimerosal, and the like. In many cases, it will be preferable to include isotonic agents, for example, sugars, polyalcohols such as manitol, sorbitol, sodium chloride in the composition. Prolonged absorption of the injectable compositions can be brought about by including in the composition an agent which delays absorption, for example, aluminum monostearate and gelatin.


[0216] Sterile injectable solutions can be prepared by incorporating the active compound (e.g., an NOVX protein or anti-NOVX antibody) in the required amount in an appropriate solvent with one or a combination of ingredients enumerated above, as required, followed by filtered sterilization. Generally, dispersions are prepared by incorporating the active compound into a sterile vehicle that contains a basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, methods of preparation are vacuum drying and freeze-drying that yields a powder of the active ingredient plus any additional desired ingredient from a previously sterile-filtered solution thereof.


[0217] Oral compositions generally include an inert diluent or an edible carrier. They can be enclosed in gelatin capsules or compressed into tablets. For the purpose of oral therapeutic administration, the active compound can be incorporated with excipients and used in the form of tablets, troches, or capsules. Oral compositions can also be prepared using a fluid carrier for use as a mouthwash, wherein the compound in the fluid carrier is applied orally and swished and expectorated or swallowed. Pharmaceutically compatible binding agents, and/or adjuvant materials can be included as part of the composition. The tablets, pills, capsules, troches and the like can contain any of the following ingredients, or compounds of a similar nature: a binder such as microcrystalline cellulose, gum tragacanth or gelatin; an excipient such as starch or lactose, a disintegrating agent such as alginic acid, Primogel, or corn starch; a lubricant such as magnesium stearate or Sterotes; a glidant such as colloidal silicon dioxide; a sweetening agent such as sucrose or saccharin; or a flavoring agent such as peppermint, methyl salicylate, or orange flavoring.


[0218] For administration by inhalation, the compounds are delivered in the form of an aerosol spray from pressured container or dispenser which contains a suitable propellant, e.g., a gas such as carbon dioxide, or a nebulizer.


[0219] Systemic administration can also be by transmucosal or transdermal means. For transmucosal or transdermal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art, and include, for example, for transmucosal administration, detergents, bile salts, and fusidic acid derivatives. Transmucosal administration can be accomplished through the use of nasal sprays or suppositories. For transdermal administration, the active compounds are formulated into ointments, salves, gels, or creams as generally known in the art.


[0220] The compounds can also be prepared in the form of suppositories (e.g., with conventional suppository bases such as cocoa butter and other glycerides) or retention enemas for rectal delivery.


[0221] In one embodiment, the active compounds are prepared with carriers that will protect the compound against rapid elimination from the body, such as a controlled release formulation, including implants and microencapsulated delivery systems. Biodegradable, biocompatible polymers can be used, such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, and polylactic acid. Methods for preparation of such formulations will be apparent to those skilled in the art. The materials can also be obtained commercially from Alza Corporation and Nova Pharmaceuticals, Inc. Liposomal suspensions (including liposomes targeted to infected cells with monoclonal antibodies to viral antigens) can also be used as pharmaceutically acceptable carriers. These can be prepared according to methods known to those skilled in the art, for example, as described in U.S. Pat. No. 4,522,811.


[0222] It is especially advantageous to formulate oral or parenteral compositions in dosage unit form for ease of administration and uniformity of dosage. Dosage unit form as used herein refers to physically discrete units suited as unitary dosages for the subject to be treated; each unit containing a predetermined quantity of active compound calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier. The specification for the dosage unit forms of the invention are dictated by and directly dependent on the unique characteristics of the active compound and the particular therapeutic effect to be achieved, and the limitations inherent in the art of compounding such an active compound for the treatment of individuals.


[0223] The nucleic acid molecules of the invention can be inserted into vectors and used as gene therapy vectors. Gene therapy vectors can be delivered to a subject by, for example, intravenous injection, local administration (see, e.g., U.S. Pat. No. 5,328,470) or by stereotactic injection (see, e.g., Chen, et al., 1994. Proc. Natl. Acad. Sci. USA 91: 3054-3057). The pharmaceutical preparation of the gene therapy vector can include the gene therapy vector in an acceptable diluent, orcan comprise a slow release matrix in which the gene delivery vehicle is imbedded. Alternatively, where the complete gene delivery vector can be produced intact from recombinant cells, e.g., retroviral vectors, the pharmaceutical preparation can include one or more cells that produce the gene delivery system.


[0224] The pharmaceutical compositions can be included in a container, pack, or dispenser together with instructions for administration.


[0225] Screening and Detection Methods


[0226] The isolated nucleic acid molecules of the invention can be used to express NOVX protein (e.g., via a recombinant expression vector in a host cell in gene therapy applications), to detect NOVX mRNA (e.g., in a biological sample) or a genetic lesion in an NOVX gene, and to modulate NOVX activity, as described further, below. In addition, the NOVX proteins can be used to screen drugs or compounds that modulate the NOVX protein activity or expression as well as to treat disorders characterized by insufficient or excessive production of NOVX protein or production of NOVX protein forms that have decreased or aberrant activity compared to NOVX wild-type protein (e.g.; diabetes (regulates insulin release); obesity (binds and transport lipids); metabolic disturbances associated with obesity, the metabolic syndrome X as well as anorexia and wasting disorders associated with chronic diseases and various cancers, and infectious disease (possesses anti-microbial activity) and the various dyslipidemias. In addition, the anti-NOVX antibodies of the invention can be used to detect and isolate NOVX proteins and modulate NOVX activity. In yet a further aspect, the invention can be used in methods to influence appetite, absorption of nutrients and the disposition of metabolic substrates in both a positive and negative fashion.


[0227] The invention further pertains to novel agents identified by the screening assays described herein and uses thereof for treatments as described, supra.


[0228] Screening Assays


[0229] The invention provides a method (also referred to herein as a “screening assay”) for identifying modulators, i.e., candidate or test compounds or agents (e.g., peptides, peptidomimetics, small molecules or other drugs) that bind to NOVX proteins or have a stimulatory or inhibitory effect on, e.g., NOVX protein expression or NOVX protein activity. The invention also includes compounds identified in the screening assays described herein.


[0230] In one embodiment, the invention provides assays for screening candidate or test compounds which bind to or modulate the activity of the membrane-bound form of an NOVX protein or polypeptide or biologically-active portion thereof. The test compounds of the invention can be obtained using any of the numerous approaches in combinatorial library methods known in the art, including: biological libraries; spatially addressable parallel solid phase or solution phase libraries; synthetic library methods requiring deconvolution; the “one-bead one-compound” library method; and synthetic library methods using affinity chromatography selection. The biological library approach is limited to peptide libraries, while the other four approaches are applicable to peptide, non-peptide oligomer or small molecule libraries of compounds. See, e.g., Lam, 1997. Anticancer Drug Design 12: 145.


[0231] A “small molecule” as used herein, is meant to refer to a composition that has a molecular weight of less than about 5 kD and most preferably less than about 4 kD. Small molecules can be, e.g., nucleic acids, peptides, polypeptides, peptidomimetics, carbohydrates, lipids or other organic or inorganic molecules. Libraries of chemical and/or biological mixtures, such as fungal, bacterial, or algal extracts, are known in the art and can be screened with any of the assays of the invention.


[0232] Examples of methods for the synthesis of molecular libraries can be found in the art, for example in: DeWitt, et al., 1993. Proc. Natl. Acad. Sci. U.S.A. 90: 6909; Erb, et al., 1994. Proc. Natl. Acad. Sci. U.S.A. 91: 11422; Zuckermann, et al., 1994. J. Med. Chem. 37: 2678; Cho, et al., 1993. Science 261: 1303; Carrell, et al., 1994. Angew. Chem. Int. Ed. Engl. 33: 2059; Carell, et al., 1994. Angew. Chem. Int. Ed. Engl. 33: 2061; and Gallop, et al., 1994. J. Med. Chem. 37:1233.


[0233] Libraries of compounds may be presented in solution (e.g., Houghten, 1992. Biotechniques 13: 412-421), or on beads (Lam, 1991. Nature 354: 82-84), on chips (Fodor, 1993. Nature 364: 555-556), bacteria (Ladner, U.S. Pat. No. 5,223,409), spores (Ladner, U.S. Pat. No. 5,233,409), plasmids (Cull, et al., 1992. Proc. Natl. Acad. Sci. USA 89: 1865-1869) or on phage (Scott and Smith, 1990. Science 249: 386-390; Devlin, 1990. Science 249: 404-406; Cwirla, et al., 1990. Proc. Natl. Acad. Sci. U.S.A. 87: 6378-6382; Felici, 1991. J. Mol. Biol. 222: 301-310; Ladner, U.S. Pat. No. 5,233,409.).


[0234] In one embodiment, an assay is a cell-based assay in which a cell which expresses a membrane-bound form of NOVX protein, or a biologically-active portion thereof, on the cell surface is contacted with a test compound and the ability of the test compound to bind to an NOVX protein determined. The cell, for example, can of mammalian origin or a yeast cell. Determining the ability of the test compound to bind to the NOVX protein can be accomplished, for example, by coupling the test compound with a radioisotope or enzymatic label such that binding of the test compound to the NOVX protein or biologically-active portion thereof can be determined by detecting the labeled compound in a complex. For example, test compounds can be labeled with 125I, 35S, 14C, or 3H, either directly or indirectly, and the radioisotope detected by direct counting of radioemission or by scintillation counting. Alternatively, test compounds can be enzymatically-labeled with, for example, horseradish peroxidase, alkaline phosphatase, or luciferase, and the enzymatic label detected by determination of conversion of an appropriate substrate to product. In one embodiment, the assay comprises contacting a cell which expresses a membrane-bound form of NOVX protein, or a biologically-active portion thereof, on the cell surface with a known compound which binds NOVX to form an assay mixture, contacting the assay mixture with a test compound, and determining the ability of the test compound to interact with an NOVX protein, wherein determining the ability of the test compound to interact with an NOVX protein comprises determining the ability of the test compound to preferentially bind to NOVX protein or a biologically-active portion thereof as compared to the known compound.


[0235] In another embodiment, an assay is a cell-based assay comprising contacting a cell expressing a membrane-bound form of NOVX protein, or a biologically-active portion thereof, on the cell surface with a test compound and determining the ability of the test compound to modulate (e.g., stimulate or inhibit) the activity of the NOVX protein or biologically-active portion thereof. Determining the ability of the test compound to modulate the activity of NOVX or a biologically-active portion thereof can be accomplished, for example, by determining the ability of the NOVX protein to bind to or interact with an NOVX target molecule. As used herein, a “target molecule” is a molecule with which an NOVX protein binds or interacts in nature, for example, a molecule on the surface of a cell which expresses an NOVX interacting protein, a molecule on the surface of a second cell, a molecule in the extracellular milieu, a molecule associated with the internal surface of a cell membrane or a cytoplasmic molecule. An NOVX target molecule can be a non-NOVX molecule or an NOVX protein or polypeptide of the invention. In one embodiment, an NOVX target molecule is a component of a signal transduction pathway that facilitates transduction of an extracellular signal (e.g. a signal generated by binding of a compound to a membrane-bound NOVX molecule) through the cell membrane and into the cell. The target, for example, can be a second intercellular protein that has catalytic activity or a protein that facilitates the association of downstream signaling molecules with NOVX.


[0236] Determining the ability of the NOVX protein to bind to or interact with an NOVX target molecule can be accomplished by one of the methods described above for determining direct binding. In one embodiment, determining the ability of the NOVX protein to bind to or interact with an NOVX target molecule can be accomplished by determining the activity of the target molecule. For example, the activity of the target molecule can be determined by detecting induction of a cellular second messenger of the target (i.e. intracellular Ca2+, diacylglycerol, IP3, etc.), detecting catalytic/enzymatic activity of the target an appropriate substrate, detecting the induction of a reporter gene (comprising an NOVX-responsive regulatory element operatively linked to a nucleic acid encoding a detectable marker, e.g., luciferase), or detecting a cellular response, for example, cell survival, cellular differentiation, or cell proliferation.


[0237] In yet another embodiment, an assay of the invention is a cell-free assay comprising contacting an NOVX protein or biologically-active portion thereof with a test compound and determining the ability of the test compound to bind to the NOVX protein or biologically-active portion thereof. Binding of the test compound to the NOVX protein can be determined either directly or indirectly as described above. In one such embodiment, the assay comprises contacting the NOVX protein or biologically-active portion thereof with a known compound which binds NOVX to form an assay mixture, contacting the assay mixture with a test compound, and determining the ability of the test compound to interact with an NOVX protein, wherein determining the ability of the test compound to interact with an NOVX protein comprises determining the ability of the test compound to preferentially bind to NOVX or biologically-active portion thereof as compared to the known compound.


[0238] In still another embodiment, an assay is a cell-free assay comprising contacting NOVX protein or biologically-active portion thereof with a test compound and determining the ability of the test compound to modulate (e.g. stimulate or inhibit) the activity of the NOVX protein or biologically-active portion thereof. Determining the ability of the test compound to modulate the activity of NOVX can be accomplished, for example, by determining the ability of the NOVX protein to bind to an NOVX target molecule by one of the methods described above for determining direct binding. In an alternative embodiment, determining the ability of the test compound to modulate the activity of NOVX protein can be accomplished by determining the ability of the NOVX protein further modulate an NOVX target molecule. For example, the catalytic/enzymatic activity of the target molecule on an appropriate substrate can be determined as described, supra.


[0239] In yet another embodiment, the cell-free assay comprises contacting the NOVX protein or biologically-active portion thereof with a known compound which binds NOVX protein to form an assay mixture, contacting the assay mixture with a test compound, and determining the ability of the test compound to interact with an NOVX protein, wherein determining the ability of the test compound to interact with an NOVX protein comprises determining the ability of the NOVX protein to preferentially bind to or modulate the activity of an NOVX target molecule.


[0240] The cell-free assays of the invention are amenable to use of both the soluble form or the membrane-bound form of NOVX protein. In the case of cell-free assays comprising the membrane-bound form of NOVX protein, it may be desirable to utilize a solubilizing agent such that the membrane-bound form of NOVX protein is maintained in solution. Examples of such solubilizing agents include non-ionic detergents such as n-octylglucoside, n-dodecylglucoside, n-dodecylmaltoside, octanoyl-N-methylglucamide, decanoyl-N-methylglucamide, Triton® X-100, Triton® X-114, Thesit®, Isotridecypoly(ethylene glycol ether)n, N-dodecyl-N,N-dimethyl-3-ammonio-1-propane sulfonate, 3-(3-cholamidopropyl) dimethylamminiol-1-propane sulfonate (CHAPS), or 3-(3-cholamidopropyl)dimethylamminiol-2-hydroxy-1-propane sulfonate (CHAPSO).


[0241] In more than one embodiment of the above assay methods of the invention, it may be desirable to immobilize either NOVX protein or its target molecule to facilitate separation of complexed from uncomplexed forms of one or both of the proteins, as well as to accommodate automation of the assay. Binding of a test compound to NOVX protein, or interaction of NOVX protein with a target molecule in the presence and absence of a candidate compound, can be accomplished in any vessel suitable for containing the reactants. Examples of such vessels include microtiter plates, test tubes, and micro-centrifuge tubes. In one embodiment, a fusion protein can be provided that adds a domain that allows one or both of the proteins to be bound to a matrix. For example, GST-NOVX fusion proteins or GST-target fusion proteins can be adsorbed onto glutathione sepharose beads (Sigma Chemical, St. Louis, Mo.) or glutathione derivatized microtiter plates, that are then combined with the test compound or the test compound and either the non-adsorbed target protein or NOVX protein, and the mixture is incubated under conditions conducive to complex formation (e.g., at physiological conditions for salt and pH). Following incubation, the beads or microtiter plate wells are washed to remove any unbound components, the matrix immobilized in the case of beads, complex determined either directly or indirectly, for example, as described, supra. Alternatively, the complexes can be dissociated from the matrix, and the level of NOVX protein binding or activity determined using standard techniques.


[0242] Other techniques for immobilizing proteins on matrices can also be used in the screening assays of the invention. For example, either the NOVX protein or its target molecule can be immobilized utilizing conjugation of biotin and streptavidin. Biotinylated NOVX protein or target molecules can be prepared from biotin-NHS (N-hydroxy-succinimide) using techniques well-known within the art (e.g., biotinylation kit, Pierce Chemicals, Rockford, Ill.), and immobilized in the wells of streptavidin-coated 96 well plates (Pierce Chemical). Alternatively, antibodies reactive with NOVX protein or target molecules, but which do not interfere with binding of the NOVX protein to its target molecule, can be derivatized to the wells of the plate, and unbound target or NOVX protein trapped in the wells by antibody conjugation. Methods for detecting such complexes, in addition to those described above for the GST-immobilized complexes, include immunodetection of complexes using antibodies reactive with the NOVX protein or target molecule, as well as enzyme-linked assays that rely on detecting an enzymatic activity associated with the NOVX protein or target molecule.


[0243] In another embodiment, modulators of NOVX protein expression are identified in a method wherein a cell is contacted with a candidate compound and the expression of NOVX mRNA or protein in the cell is determined. The level of expression of NOVX mRNA or protein in the presence of the candidate compound is compared to the level of expression of NOVX mRNA or protein in the absence of the candidate compound. The candidate compound can then be identified as a modulator of NOVX mRNA or protein expression based upon this comparison. For example, when expression of NOVX mRNA or protein is greater (ie., statistically significantly greater) in the presence of the candidate compound than in its absence, the candidate compound is identified as a stimulator of NOVX mRNA or protein expression. Alternatively, when expression of NOVX mRNA or protein is less (statistically significantly less) in the presence of the candidate compound than in its absence, the candidate compound is identified as an inhibitor of NOVX mRNA or protein expression. The level of NOVX mRNA or protein expression in the cells can be determined by methods described herein for detecting NOVX mRNA or protein.


[0244] In yet another aspect of the invention, the NOVX proteins can be used as “bait proteins” in a two-hybrid assay or three hybrid assay (see, e.g., U.S. Pat. No. 5,283,317; Zervos, et al., 1993. Cell 72: 223-232; Madura, et al., 1993. J. Biol. Chem. 268: 12046-12054; Bartel, et al., 1993. Biotechniques 14: 920-924; Iwabuchi, et al., 1993. Oncogene 8: 1693-1696; and Brent WO 94/10300), to identify other proteins that bind to or interact with NOVX (“NOVX-binding proteins” or “NOVX-bp”) and modulate NOVX activity. Such NOVX-binding proteins are also likely to be involved in the propagation of signals by the NOVX proteins as, for example, upstream or downstream elements of the NOVX pathway.


[0245] The two-hybrid system is based on the modular nature of most transcription factors, which consist of separable DNA-binding and activation domains. Briefly, the assay utilizes two different DNA constructs. In one construct, the gene that codes for NOVX is fused to a gene encoding the DNA binding domain of a known transcription factor (e.g., GALA). In the other construct, a DNA sequence, from a library of DNA sequences, that encodes an unidentified protein (“prey” or “sample”) is fused to a gene that codes for the activation domain of the known transcription factor. If the “bait” and the “prey” proteins are able to interact, in vivo, forming an NOVX-dependent complex, the DNA-binding and activation domains of the transcription factor are brought into close proximity. This proximity allows transcription of a reporter gene (e.g., LacZ) that is operably linked to a transcriptional regulatory site responsive to the transcription factor. Expression of the reporter gene can be detected and cell colonies containing the functional transcription factor can be isolated and used to obtain the cloned gene that encodes the protein which interacts with NOVX.


[0246] The invention further pertains to novel agents identified by the aforementioned screening assays and uses thereof for treatments as described herein.


[0247] Detection Assays


[0248] Portions or fragments of the cDNA sequences identified herein (and the corresponding complete gene sequences) can be used in numerous ways as polynucleotide reagents. By way of example, and not of limitation, these sequences can be used to: (i) map their respective genes on a chromosome; and, thus, locate gene regions associated with genetic disease; (ii) identify an individual from a minute biological sample (tissue typing); and (iii) aid in forensic identification of a biological sample. Some of these applications are described in the subsections, below.


[0249] Chromosome Mapping


[0250] Once the sequence (or a portion of the sequence) of a gene has been isolated, this sequence can be used to map the location of the gene on a chromosome. This process is called chromosome mapping. Accordingly, portions or fragments of the NOVX sequences, SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178, or fragments or derivatives thereof, can be used to map the location of the NOVX genes, respectively, on a chromosome. The mapping of the NOVX sequences to chromosomes is an important first step in correlating these sequences with genes associated with disease.


[0251] Briefly, NOVX genes can be mapped to chromosomes by preparing PCR primers (preferably 15-25 bp in length) from the NOVX sequences. Computer analysis of the NOVX, sequences can be used to rapidly select primers that do not span more than one exon in the genomic DNA, thus complicating the amplification process. These primers can then be used for PCR screening of somatic cell hybrids containing individual human chromosomes. Only those hybrids containing the human gene corresponding to the NOVX sequences will yield an amplified fragment.


[0252] Somatic cell hybrids are prepared by fusing somatic cells from different mammals (e.g., human and mouse cells). As hybrids of human and mouse cells grow and divide, they gradually lose human chromosomes in random order, but retain the mouse chromosomes. By using media in which mouse cells cannot grow, because they lack a particular enzyme, but in which human cells can, the one human chromosome that contains the gene encoding the needed enzyme will be retained. By using various media, panels of hybrid cell lines can be established. Each cell line in a panel contains either a single human chromosome or a small number of human chromosomes, and a full set of mouse chromosomes, allowing easy mapping of individual genes to specific human chromosomes. See, e.g., D'Eustachio, et al., 1983. Science 220: 919-924. Somatic cell hybrids containing only fragments of human chromosomes can also be produced by using human chromosomes with translocations and deletions.


[0253] PCR mapping of somatic cell hybrids is a rapid procedure for assigning a particular sequence to a particular chromosome. Three or more sequences can be assigned per day using a single thermal cycler. Using the NOVX sequences to design oligonucleotide primers, sub-localization can be achieved with panels of fragments from specific chromosomes.


[0254] Fluorescence in situ hybridization (FISH) of a DNA sequence to a metaphase chromosomal 0.4 z spread can further be used to provide a precise chromosomal location in one step. Chromosome spreads can be made using cells whose division has been blocked in metaphase by a chemical like colcemid that disrupts the mitotic spindle. The chromosomes can be treated briefly with trypsin, and then stained with Giemsa. A pattern of light and dark bands develops on each chromosome, so that the chromosomes can be identified individually. The FISH technique can be used with a DNA sequence as short as 500 or 600 bases. However, clones larger than 1,000 bases have a higher likelihood of binding to a unique chromosomal location with sufficient signal intensity for simple detection. Preferably 1,000 bases, and more preferably 2,000 bases, will suffice to get good results at a reasonable amount of time. For a review of this technique, see, Verma, et al., HUMAN CHROMOSOMES: A MANUAL OF BASIC TECHNIQUES (Pergamon Press, New York 1988).


[0255] Reagents for chromosome mapping can be used individually to mark a single chromosome or a single site on that chromosome, or panels of reagents can be used for marking multiple sites and/or multiple chromosomes. Reagents corresponding to noncoding regions of the genes actually are preferred for mapping purposes. Coding sequences are more likely to be conserved within gene families, thus increasing the chance of cross hybridizations during chromosomal mapping.


[0256] Once a sequence has been mapped to a precise chromosomal location, the physical position of the sequence on the chromosome can be correlated with genetic map data. Such data are found, e.g., in McKusick, MENDELIAN INHERITANCE IN MAN, available on-line through Johns Hopkins University Welch Medical Library). The relationship between genes and disease, mapped to the same chromosomal region, can then be identified through linkage analysis (co-inheritance of physically adjacent genes), described in, e.g., Egeland, et al., 1987. Nature, 325: 783-787.


[0257] Moreover, differences in the DNA sequences between individuals affected and unaffected with a disease associated with the NOVX gene, can be determined. If a mutation is observed in some or all of the affected individuals but not in any unaffected individuals, then the mutation is likely to be the causative agent of the particular disease. Comparison of affected and unaffected individuals generally involves first looking for structural alterations in the chromosomes, such as deletions or translocations that are visible from chromosome spreads or detectable using PCR based on that DNA sequence. Ultimately, complete sequencing of genes from several individuals can be performed to confirm the presence of a mutation and to distinguish mutations from polymorphisms.


[0258] Tissue Typing


[0259] The NOVX sequences of the invention can also be used to identify individuals from minute biological samples. In this technique, an individual's genomic DNA is digested with one or more restriction enzymes, and probed on a Southern blot to yield unique bands for identification. The sequences of the invention are useful as additional DNA markers for RFLP (“restriction fragment length polymorphisms,” described in U.S. Pat. No. 5,272,057).


[0260] Furthermore, the sequences of the invention can be used to provide an alternative technique that determines the actual base-by-base DNA sequence of selected portions of an individual's genome. Thus, the NOVX sequences described herein can be used to prepare two PCR primers from the 5′- and 3′-termini of the sequences. These primers can then be used to amplify an individual's DNA and subsequently sequence it.


[0261] Panels of corresponding DNA sequences from individuals, prepared in this manner, can provide unique individual identifications, as each individual will have a unique set of such DNA sequences due to allelic differences. The sequences of the invention can be used to obtain such identification sequences from individuals and from tissue. The NOVX sequences of the invention uniquely represent portions of the human genome. Allelic variation occurs to some degree in the coding regions of these sequences, and to a greater degree in the noncoding regions. It is estimated that allelic variation between individual humans occurs with a frequency of about once per each 500 bases. Much of the allelic variation is due to single nucleotide polymorphisms (SNPs), which include restriction fragment length polymorphisms (RFLPs).


[0262] Each of the sequences described herein can, to some degree, be used as a standard against which DNA from an individual can be compared for identification purposes. Because greater numbers of polymorphisms occur in the noncoding regions, fewer sequences are necessary to differentiate individuals. The noncoding sequences can comfortably provide positive individual identification with a panel of perhaps 10 to 1,000 primers that each yield a noncoding amplified sequence of 100 bases. If predicted coding sequences, such as those in SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178 are used, a more appropriate number of primers for positive individual identification would be 500-2,000.


[0263] Predictive Medicine


[0264] The invention also pertains to the field of predictive medicine in which diagnostic assays, prognostic assays, pharmacogenomics, and monitoring clinical trials are used for prognostic (predictive) purposes to thereby treat an individual prophylactically. Accordingly, one aspect of the invention relates to diagnostic assays for determining NOVX protein and/or nucleic acid expression as well as NOVX activity, in the context of a biological sample (e.g., blood, serum, cells, tissue) to thereby determine whether an individual is afflicted with a disease or disorder, or is at risk of developing a disorder, associated with aberrant NOVX expression or activity. The disorders include metabolic disorders, diabetes, obesity, infectious disease, anorexia, cancer-associated cachexia, cancer, neurodegenerative disorders, Alzheimer's Disease, Parkinson's Disorder, immune disorders, and hematopoietic disorders, and the various dyslipidemias, metabolic disturbances associated with obesity, the metabolic syndrome X and wasting disorders associated with chronic diseases and various cancers. The invention also provides for prognostic (or predictive) assays for determining whether an individual is at risk of developing a disorder associated with NOVX protein, nucleic acid expression or activity. For example, mutations in an NOVX gene can be assayed in a biological sample. Such assays can be used for prognostic or predictive purpose to thereby prophylactically treat an individual prior to the onset of a disorder characterized by or associated with NOVX protein, nucleic acid expression, or biological activity.


[0265] Another aspect of the invention provides methods for determining NOVX protein, nucleic acid expression or activity in an individual to thereby select appropriate therapeutic or prophylactic agents for that individual (referred to herein as “pharmacogenomics”). Pharmacogenomics allows for the selection of agents (e.g., drugs) for therapeutic or prophylactic treatment of an individual based on the genotype of the individual (e.g., the genotype of the individual examined to determine the ability of the individual to respond to a particular agent.)


[0266] Yet another aspect of the invention pertains to monitoring the influence of agents (e.g., drugs, compounds) on the expression or activity of NOVX in clinical trials.


[0267] These and other agents are described in further detail in the following sections.


[0268] Diagnostic Assays


[0269] An exemplary method for detecting the presence or absence of NOVX in a biological sample involves obtaining a biological sample from a test subject and contacting the biological sample with a compound or an agent capable of detecting NOVX protein or nucleic acid (e.g., mRNA, genomic DNA) that encodes NOVX protein such that the presence of NOVX is detected in the biological sample. An agent for detecting NOVX mRNA or genomic DNA is a labeled nucleic acid probe capable of hybridizing to NOVX mRNA or genomic DNA. The nucleic acid probe can be, for example, a full-length NOVX nucleic acid, such as the nucleic acid of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178, or a portion thereof, such as an oligonucleotide of at least 15, 30, 50, 100, 250 or 500 nucleotides in length and sufficient to specifically hybridize under stringent conditions to NOVX mRNA or genomic DNA. Other suitable probes for use in the diagnostic assays of the invention are described herein.


[0270] An agent for detecting NOVX protein is an antibody capable of binding to NOVX protein, preferably an antibody with a detectable label. Antibodies can be polyclonal, or more preferably, monoclonal. An intact antibody, or a fragment thereof (e.g., Fab or F(ab′)2) can be used. The term “labeled”, with regard to the probe or antibody, is intended to encompass direct labeling of the probe or antibody by coupling (ie., physically linking) a detectable substance to the probe or antibody, as well as indirect labeling of the probe or antibody by reactivity with another reagent that is directly labeled. Examples of indirect labeling include detection of a primary antibody using a fluorescently-labeled secondary antibody and end-labeling of a DNA probe with biotin such that it can be detected with fluorescently-labeled streptavidin. The term “biological sample” is intended to include tissues, cells and biological fluids isolated from a subject, as well as tissues, cells and fluids present within a subject. That is, the detection method of the invention can be used to detect NOVX mRNA, protein, or genomic DNA in a biological sample in vitro as well as in vivo. For example, in vitro techniques for detection of NOVX mRNA include Northern hybridizations and in situ hybridizations. In vitro techniques for detection of NOVX protein include enzyme linked immunosorbent assays (ELISAs), Western blots, immunoprecipitations, and immunofluorescence. In vitro techniques for detection of NOVX genomic DNA include Southern hybridizations. Furthermore, in vivo techniques for detection of NOVX protein include introducing into a subject a labeled anti-NOVX antibody. For example, the antibody can be labeled with a radioactive marker whose presence and location in a subject can be detected by standard imaging techniques.


[0271] In one embodiment, the biological sample contains protein molecules from the test subject. Alternatively, the biological sample can contain mRNA molecules from the test subject or genomic DNA molecules from the test subject. A preferred biological sample is a peripheral blood leukocyte sample isolated by conventional means from a subject.


[0272] In another embodiment, the methods further involve obtaining a control biological sample from a control subject, contacting the control sample with a compound or agent capable of detecting NOVX protein, mRNA, or genomic DNA, such that the presence of NOVX protein, mRNA or genomic DNA is detected in the biological sample, and comparing the presence of NOVX protein, mRNA or genomic DNA in the control sample with the presence of NOVX protein, mRNA or genomic DNA in the test sample.


[0273] The invention also encompasses kits for detecting the presence of NOVX in a biological sample. For example, the kit can comprise: a labeled compound or agent capable of detecting NOVX protein or mRNA in a biological sample; means for determining the amount of NOVX in the sample; and means for comparing the amount of NOVX in the sample with a standard. The compound or agent can be packaged in a suitable container. The kit can further comprise instructions for using the kit to detect NOVX protein or nucleic acid.


[0274] Prognostic Assays


[0275] The diagnostic methods described herein can furthermore be utilized to identify subjects having or at risk of developing a disease or disorder associated with aberrant NOVX expression or activity. For example, the assays described herein, such as the preceding diagnostic assays or the following assays, can be utilized to identify a subject having or at risk of developing a disorder associated with NOVX protein, nucleic acid expression or activity. Alternatively, the prognostic assays can be utilized to identify a subject having or at risk for developing a disease or disorder. Thus, the invention provides a method for identifying a disease or disorder associated with aberrant NOVX expression or activity in which a test sample is obtained from a subject and NOVX protein or nucleic acid (e.g., mRNA, genomic DNA) is detected, wherein the presence of NOVX protein or nucleic acid is diagnostic for a subject having or at risk of developing a disease or disorder associated with aberrant NOVX expression or activity. As used herein, a “test sample” refers to a biological sample obtained from a subject of interest. For example, a test sample can be a biological fluid (e.g., serum), cell sample, or tissue.


[0276] Furthermore, the prognostic assays described herein can be used to determine whether a subject can be administered an agent (e.g., an agonist, antagonist, peptidomimetic, protein, peptide, nucleic acid, small molecule, or other drug candidate) to treat a disease or disorder associated with aberrant NOVX expression or activity. For example, such methods can be used to determine whether a subject can be effectively treated with an agent for a disorder. Thus, the invention provides methods for determining whether a subject can be effectively treated with an agent for a disorder associated with aberrant NOVX expression or activity in which a test sample is obtained and NOVX protein or nucleic acid is detected (e.g., wherein the presence of NOVX protein or nucleic acid is diagnostic for a subject that can be administered the agent to treat a disorder associated with aberrant NOVX expression or activity).


[0277] The methods of the invention can also be used to detect genetic lesions in an NOVX gene, thereby determining if a subject with the lesioned gene is at risk for a disorder characterized by aberrant cell proliferation and/or differentiation. In various embodiments, the methods include detecting, in a sample of cells from the subject, the presence or absence of a genetic lesion characterized by at least one of an alteration affecting the integrity of a gene encoding an NOVX-protein, or the misexpression of the NOVX gene. For example, such genetic lesions can be detected by ascertaining the existence of at least one of: (i) a deletion of one or more nucleotides from an NOVX gene; (ii) an addition of one or more nucleotides to an NOVX gene; (iii) a substitution of one or more nucleotides of an NOVX gene, (iv) a chromosomal rearrangement of an NOVX gene; (v) an alteration in the level of a messenger RNA transcript of an NOVX gene, (vi) aberrant modification of an NOVX gene, such as of the methylation pattern of the genomic DNA, (vii) the presence of a non-wild-type splicing pattern of a messenger RNA transcript of an NOVX gene, (viii) a non-wild-type level of an NOVX protein, (ix) allelic loss of an NOVX gene, and (x) inappropriate post-translational modification of an NOVX protein. As described herein, there are a large number of assay techniques known in the art which can be used for detecting lesions in an NOVX gene. A preferred biological sample is a peripheral blood leukocyte sample isolated by conventional means from a subject. However, any biological sample containing nucleated cells may be used, including, for example, buccal mucosal cells.


[0278] In certain embodiments, detection of the lesion involves the use of a probe/primer in a polymerase chain reaction (PCR) (see, e.g., U.S. Pat. Nos. 4,683,195 and 4,683,202), such as anchor PCR or RACE PCR, or, alternatively, in a ligation chain reaction (LCR) (see, e.g., Landegran, et al., 1988. Science 241: 1077-1080; and Nakazawa, et al., 1994. Proc. Natl. Acad. Sci. USA 91: 360-364), the latter of which can be particularly useful for detecting point mutations in the NOVX-gene (see, Abravaya, et al., 1995. Nucl. Acids Res. 23: 675-682). This method can include the steps of collecting a sample of cells from a patient, isolating nucleic acid (e.g., genomic, mRNA or both) from the cells of the sample, contacting the nucleic acid sample with one or more primers that specifically hybridize to an NOVX gene under conditions such that hybridization and amplification of the NOVX gene (if present) occurs, and detecting the presence or absence of an amplification product, or detecting the size of the amplification product and comparing the length to a control sample. It is anticipated that PCR and/or LCR may be desirable to use as a preliminary amplification step in conjunction with any of the techniques used for detecting mutations described herein.


[0279] Alternative amplification methods include: self sustained sequence replication (see, Guatelli, et al., 1990. Proc. Natl. Acad. Sci. USA 87: 1874-1878), transcriptional amplification system (see, Kwoh, et al., 1989. Proc. Natl. Acad. Sci. USA 86: 1173-1177); Qβ Replicase (see, Lizardi, et al, 1988. BioTechnology 6: 1197), or any other nucleic acid amplification method, followed by the detection of the amplified molecules using techniques well known to those of skill in the art. These detection schemes are especially useful for the detection of nucleic acid molecules if such molecules are present in very low numbers.


[0280] In an alternative embodiment, mutations in an NOVX gene from a sample cell can be identified by alterations in restriction enzyme cleavage patterns. For example, sample and control DNA is isolated, amplified (optionally), digested with one or more restriction endonucleases, and fragment length sizes are determined by gel electrophoresis and compared. Differences in fragment length sizes between sample and control DNA indicates mutations in the sample DNA. Moreover, the use of sequence specific ribozymes (see, e.g., U.S. Pat. No. 5,493,531) can be used to score for the presence of specific mutations by development or loss of a ribozyme cleavage site.


[0281] In other embodiments, genetic mutations in NOVX can be identified by hybridizing a sample and control nucleic acids, e.g., DNA or RNA, to high-density arrays containing hundreds or thousands of oligonucleotides probes. See, e.g., Cronin, et al., 1996. Human Mutation 7: 244-255; Kozal, et al., 1996. Nat. Med. 2: 753-759. For example, genetic mutations in NOVX can be identified in two dimensional arrays containing light-generated DNA probes as described in Cronin, et al., supra. Briefly, a first hybridization array of probes can be used to scan through long stretches of DNA in a sample and control to identify base changes between the sequences by making linear arrays of sequential overlapping probes. This step allows the identification of point mutations. This is followed by a second hybridization array that allows the characterization of specific mutations by using smaller, specialized probe arrays complementary to all variants or mutations detected. Each mutation array is composed of parallel probe sets, one complementary to the wild-type gene and the other complementary to the mutant gene.


[0282] In yet another embodiment, any of a variety of sequencing reactions known in the art can be used to directly sequence the NOVX gene and detect mutations by comparing the sequence of the sample NOVX with the corresponding wild-type (control) sequence. Examples of sequencing reactions include those based on techniques developed by Maxim and Gilbert, 1977. Proc. Natl. Acad. Sci. USA 74: 560 or Sanger, 1977. Proc. Natl. Acad. Sci. USA 74: 5463. It is also contemplated that any of a variety of automated sequencing procedures can be utilized when performing the diagnostic assays (see, e.g., Naeve, et al., 1995. Biotechniques 19: 448), including sequencing by mass spectrometry (see, e.g., PCT International Publication No. WO 94/16101; Cohen, et al., 1996. Adv. Chromatography 36: 127-162; and Griffin, et al., 1993. Appl. Biochem. Biotechnol. 38: 147-159).


[0283] Other methods for detecting mutations in the NOVX gene include methods in which protection from cleavage agents is used to detect mismatched bases in RNA/RNA or RNA/DNA heteroduplexes. See, e.g., Myers, et al., 1985. Science 230: 1242. In general, the art technique of “mismatch cleavage” starts by providing heteroduplexes of formed by hybridizing (labeled) RNA or DNA containing the wild-type NOVX sequence with potentially mutant RNA or DNA obtained from a tissue sample. The double-stranded duplexes are treated with an agent that cleaves single-stranded regions of the duplex such as which will exist due to basepair mismatches between the control and sample strands. For instance, RNA/DNA duplexes can be treated with RNase and DNA/DNA hybrids treated with S1 nuclease to enzymatically digesting the mismatched regions. In other embodiments, either DNA/DNA or RNA/DNA duplexes can be treated with hydroxylamine or osmium tetroxide and with piperidine in order to digest mismatched regions. After digestion of the mismatched regions, the resulting material is then separated by size on denaturing polyacrylamide gels to determine the site of mutation. See, e.g., Cotton, et al., 1988. Proc. Natl. Acad. Sci. USA 85: 4397; Saleeba, et al., 1992. Methods Enzymol. 217: 286-295. In an embodiment, the control DNA or RNA can be labeled for detection.


[0284] In still another embodiment, the mismatch cleavage reaction employs one or more proteins that recognize mismatched base pairs in double-stranded DNA (so called “DNA mismatch repair” enzymes) in defined systems for detecting and mapping point mutations in NOVX cDNAs obtained from samples of cells. For example, the mutY enzyme of E. coli cleaves A at G/A mismatches and the thymidine DNA glycosylase from HeLa cells cleaves T at G/T mismatches. See, e.g., Hsu, et al., 1994. Carcinogenesis 15: 1657-1662. According to an exemplary embodiment, a probe based on an NOVX sequence, e.g. a wild-type NOVX sequence, is hybridized to a cDNA or other DNA product from a test cell(s). The duplex is treated with a DNA mismatch repair enzyme, and the cleavage products, if any, can be detected from electrophoresis protocols or the like. See, e.g., U.S. Pat. No. 5,459,039.


[0285] In other embodiments, alterations in electrophoretic mobility will be used to identify mutations in NOVX genes. For example, single strand conformation polymorphism (SSCP) may be used to detect differences in electrophoretic mobility between mutant and wild type nucleic acids. See, e.g., Orita, et al., 1989. Proc. Natl. Acad. Sci. USA: 86: 2766; Cotton, 1993. Mutat. Res. 285: 125-144; Hayashi, 1992. Genet. Anal. Tech. Appl. 9: 73-79. Single-stranded DNA fragments of sample and control NOVX nucleic acids will be denatured and allowed to renature. The secondary structure of single-stranded nucleic acids varies according to sequence, the resulting alteration in electrophoretic mobility enables the detection of even a single base change. The DNA fragments may be labeled or detected with labeled probes. The sensitivity of the assay may be enhanced by using RNA (rather than DNA), in which the secondary structure is more sensitive to a change in sequence. In one embodiment, the subject method utilizes heteroduplex analysis to separate double stranded heteroduplex molecules on the basis of changes in electrophoretic mobility. See, e.g., Keen, et al., 1991. Trends Genet. 7: 5.


[0286] In yet another embodiment, the movement of mutant or wild-type fragments in polyacrylamide gels containing a gradient of denaturant is assayed using denaturing gradient gel electrophoresis (DGGE). See, e.g., Myers, et al., 1985. Nature 313: 495. When DGGE is used as the method of analysis, DNA will be modified to insure that it does not completely denature, for example by adding a GC clamp of approximately 40 bp of high-melting GC-rich DNA by PCR. In a further embodiment, a temperature gradient is used in place of a denaturing gradient to identify differences in the mobility of control and sample DNA. See, e.g., Rosenbaum and Reissner, 1987. Biophys. Chem. 265: 12753.


[0287] Examples of other techniques for detecting point mutations include, but are not limited to, selective oligonucleotide hybridization, selective amplification, or selective primer extension. For example, oligonucleotide primers may be prepared in which the known mutation is placed centrally and then hybridized to target DNA under conditions that permit hybridization only if a perfect match is found. See, e.g., Saiki, et al., 1986. Nature 324: 163; Saiki, et al., 1989. Proc. Natl. Acad. Sci. USA 86: 6230. Such allele specific oligonucleotides are hybridized to PCR amplified target DNA or a number of different mutations when the oligonucleotides are attached to the hybridizing membrane and hybridized with labeled target DNA.


[0288] Alternatively, allele specific amplification technology that depends on selective PCR amplification may be used in conjunction with the instant invention. Oligonucleotides used as primers for specific amplification may carry the mutation of interest in the center of the molecule (so that amplification depends on differential hybridization; see, e.g., Gibbs, et al., 1989. Nucl. Acids Res. 17: 2437-2448) or at the extreme 3′-terminus of one primer where, under appropriate conditions, mismatch can prevent, or reduce polymerase extension (see, e.g., Prossner, 1993. Tibtech. 11: 238). In addition it may be desirable to introduce a novel restriction site in the region of the mutation to create cleavage-based detection. See, e.g., Gasparini, et al., 1992. Mol. Cell Probes 6: 1. It is anticipated that in certain embodiments amplification may also be performed using Taq ligase for amplification. See, e.g., Barany, 1991. Proc. Natl. Acad. Sci. USA 88: 189. In such cases, ligation will occur only if there is a perfect match at the 3′-terminus of the 5′ sequence, making it possible to detect the presence of a known mutation at a specific site by looking for the presence or absence of amplification.


[0289] The methods described herein may be performed, for example, by utilizing pre-packaged diagnostic kits comprising at least one probe nucleic acid or antibody reagent described herein, which may be conveniently used, e.g., in clinical settings to diagnose patients exhibiting symptoms or family history of a disease or illness involving an NOVX gene.


[0290] Furthermore, any cell type or tissue, preferably peripheral blood leukocytes, in which NOVX is expressed may be utilized in the prognostic assays described herein. However, any biological sample containing nucleated cells may be used, including, for example, buccal mucosal cells.


[0291] Pharmacogenomics


[0292] Agents, or modulators that have a stimulatory or inhibitory effect on NOVX activity (e.g., NOVX gene expression), as identified by a screening assay described herein can be administered to individuals to treat (prophylactically or therapeutically) disorders (The disorders include metabolic disorders, diabetes, obesity, infectious disease, anorexia, cancer-associated cachexia, cancer, neurodegenerative disorders, Alzheimer's Disease, Parkinson's Disorder, immune disorders, and hematopoietic disorders, and the various dyslipidemias, metabolic disturbances associated with obesity, the metabolic syndrome X and wasting disorders associated with chronic diseases and various cancers.) In conjunction with such treatment, the pharmacogenomics (i.e., the study of the relationship between an individual's genotype and that individual's response to a foreign compound or drug) of the individual may be considered. Differences in metabolism of therapeutics can lead to severe toxicity or therapeutic failure by altering the relation between dose and blood concentration of the pharmacologically active drug. Thus, the pharmacogenomics of the individual permits the selection of effective agents (e.g., drugs) for prophylactic or therapeutic treatments based on a consideration of the individual's genotype. Such pharmacogenomics can further be used to determine appropriate dosages and therapeutic regimens. Accordingly, the activity of NOVX protein, expression of NOVX nucleic acid, or mutation content of NOVX genes in an individual can be determined to thereby select appropriate agent(s) for therapeutic or prophylactic treatment of the individual.


[0293] Pharmacogenomics deals with clinically significant hereditary variations in the response to drugs due to altered drug disposition and abnormal action in affected persons. See e.g., Eichelbaum, 1996. Clin. Exp. Pharmacol. Physiol., 23: 983-985; Linder, 1997. Clin. Chem., 43: 254-266. In general, two types of pharmacogenetic conditions can be differentiated. Genetic conditions transmitted as a single factor altering the way drugs act on the body (altered drug action) or genetic conditions transmitted as single factors altering the way the body acts on drugs (altered drug metabolism). These pharmacogenetic conditions can occur either as rare defects or as polymorphisms. For example, glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common inherited enzymopathy in which the main clinical complication is hemolysis after ingestion of oxidant drugs (anti-malarials, sulfonamides, analgesics, nitrofurans) and consumption of fava beans.


[0294] As an illustrative embodiment, the activity of drug metabolizing enzymes is a major determinant of both the intensity and duration of drug action. The discovery of genetic polymorphisms of drug metabolizing enzymes (e.g., N-acetyltransferase 2 (NAT 2) and cytochrome PREGNANCY ZONE PROTEIN PRECURSOR enzymes CYP2D6 and CYP2C19) has provided an explanation as to why some patients do not obtain the expected drug effects or show exaggerated drug response and serious toxicity after taking the standard and safe dose of a drug. These polymorphisms are expressed in two phenotypes in the population, the extensive metabolizer (EM) and poor metabolizer (PM). The prevalence of PM is different among different populations. For example, the gene coding for CYP2D6 is highly polymorphic and several mutations have been identified in PM, which all lead to the absence of functional CYP2D6. Poor metabolizers of CYP2D6 and CYP2C 19 quite frequently experience exaggerated drug response and side effects when they receive standard doses. If a metabolite is the active therapeutic moiety, PM show no therapeutic response, as demonstrated for the analgesic effect of codeine mediated by its CYP2D6-formed metabolite morphine. At the other extreme are the so called ultra-rapid metabolizers who do not respond to standard doses. Recently, the molecular basis of ultra-rapid metabolism has been identified to be due to CYP2D6 gene amplification. Thus, the activity of NOVX protein, expression of NOVX nucleic acid, or mutation content of NOVX genes in an individual can be determined to thereby select appropriate agent(s) for therapeutic or prophylactic treatment of the individual. In addition, pharmacogenetic studies can be used to apply genotyping of polymorphic alleles encoding drug-metabolizing enzymes to the identification of an individual's drug responsiveness phenotype. This knowledge, when applied to dosing or drug selection, can avoid adverse reactions or therapeutic failure and thus enhance therapeutic or prophylactic efficiency when treating a subject with an NOVX modulator, such as a modulator identified by one of the exemplary screening assays described herein.


[0295] Monitoring of Effects During Clinical Trials


[0296] Monitoring the influence of agents (e.g., drugs, compounds) on the expression or activity of NOVX (e.g., the ability to modulate aberrant cell proliferation and/or differentiation) can be applied not only in basic drug screening, but also in clinical trials.


[0297] For example, the effectiveness of an agent determined by a screening assay as described herein to increase NOVX gene expression, protein levels, or upregulate NOVX activity, can be monitored in clinical trails of subjects exhibiting decreased NOVX gene expression, protein levels, or downregulated NOVX activity. Alternatively, the effectiveness of an agent determined by a screening assay to decrease NOVX gene expression, protein levels, or downregulate NOVX activity, can be monitored in clinical trails of subjects exhibiting increased NOVX gene expression, protein levels, or upregulated NOVX activity. In such clinical trials, the expression or activity of NOVX and, preferably, other genes that have been implicated in, for example, a cellular proliferation or immune disorder can be used as a “read out” or markers of the immune responsiveness of a particular cell.


[0298] By way of example, and not of limitation, genes, including NOVX, that are modulated in cells by treatment with an agent (e.g., compound, drug or small molecule) that modulates NOVX activity (e.g., identified in a screening assay as described herein) can be identified. Thus, to study the effect of agents on cellular proliferation disorders, for example, in a clinical trial, cells can be isolated and RNA prepared and analyzed for the levels of expression of NOVX and other genes implicated in the disorder. The levels of gene expression (i.e., a gene expression pattern) can be quantified by Northern blot analysis or RT-PCR, as described herein, or alternatively by measuring the amount of protein produced, by one of the methods as described herein, or by measuring the levels of activity of NOVX or other genes. In this manner, the gene expression pattern can serve as a marker, indicative of the physiological response of the cells to the agent. Accordingly, this response state may be determined before, and at various points during, treatment of the individual with the agent.


[0299] In one embodiment, the invention provides a method for monitoring the effectiveness of treatment of a subject with an agent (e.g., an agonist, antagonist, protein, peptide, peptidomimetic, nucleic acid, small molecule, or other drug candidate identified by the screening assays described herein) comprising the steps of (i) obtaining a pre-administration sample from a subject prior to administration of the agent; (ii) detecting the level of expression of an NOVX protein, mRNA, or genomic DNA in the preadministration sample; (iii) obtaining one or more post-administration samples from the subject; (iv) detecting the level of expression or activity of the NOVX protein, mRNA, or genomic DNA in the post-administration samples; (v) comparing the level of expression or activity of the NOVX protein, mRNA, or genomic DNA in the pre-administration sample with the NOVX protein, mRNA, or genomic DNA in the post administration sample or samples; and (vi) altering the administration of the agent to the subject accordingly. For example, increased administration of the agent may be desirable to increase the expression or activity of NOVX to higher levels than detected, i.e., to increase the effectiveness of the agent. Alternatively, decreased administration of the agent may be desirable to decrease expression or activity of NOVX to lower levels than detected, i.e., to decrease the effectiveness of the agent.


[0300] Methods of Treatment


[0301] The invention provides for both prophylactic and therapeutic methods of treating a subject at risk of (or susceptible to) a disorder or having a disorder associated with aberrant NOVX expression or activity. The disorders include cardiomyopathy, atherosclerosis, hypertension, congenital heart defects, aortic stenosis, atrial septal defect (ASD), atrioventricular (A-V) canal defect, ductus arteriosus, pulmonary stenosis, subaortic stenosis, ventricular septal defect (VSD), valve diseases, tuberous sclerosis, scleroderma, obesity, transplantation, adrenoleukodystrophy, congenital adrenal hyperplasia, prostate cancer, neoplasm; adenocarcinoma, lymphoma, uterus cancer, fertility, hemophilia, hypercoagulation, idiopathic thrombocytopenic purpura, immunodeficiencies, graft versus host disease, AIDS, bronchial asthma, Crohn's disease; multiple sclerosis, treatment of Albright Hereditary Ostoeodystrophy, and other diseases, disorders and conditions of the like.


[0302] These methods of treatment will be discussed more fully, below.


[0303] Disease and Disorders


[0304] Diseases and disorders that are characterized by increased (relative to a subject not suffering from the disease or disorder) levels or biological activity may be treated with Therapeutics that antagonize (i.e., reduce or inhibit) activity. Therapeutics that antagonize activity may be administered in a therapeutic or prophylactic manner. Therapeutics that may be utilized include, but are not limited to: (i) an aforementioned peptide, or analogs, derivatives, fragments or homologs thereof; (ii) antibodies to an aforementioned peptide; (iii) nucleic acids encoding an aforementioned peptide; (iv) administration of antisense nucleic acid and nucleic acids that are “dysfunctional” (i.e., due to a heterologous insertion within the coding sequences of coding sequences to an aforementioned peptide) that are utilized to “knockout” endogenous function of an aforementioned peptide by homologous recombination (see, e.g., Capecchi, 1989. Science 244: 1288-1292); or (v) modulators (i.e., inhibitors, agonists and antagonists, including additional peptide mimetic of the invention or antibodies specific to a peptide of the invention) that alter the interaction between an aforementioned peptide and its binding partner.


[0305] Diseases and disorders that are characterized by decreased (relative to a subject not suffering from the disease or disorder) levels or biological activity may be treated with Therapeutics that increase (ie., are agonists to) activity. Therapeutics that upregulate activity may be administered in a therapeutic or prophylactic manner. Therapeutics that may be utilized include, but are not limited to, an aforementioned peptide, or analogs, derivatives, fragments or homologs thereof; or an agonist that increases bioavailability.


[0306] Increased or decreased levels can be readily detected by quantifying peptide and/or RNA, by obtaining a patient tissue sample (e.g., from biopsy tissue) and assaying it in vitro for RNA or peptide levels, structure and/or activity of the expressed peptides (or mRNAs of an aforementioned peptide). Methods that are well-known within the art include, but are not limited to, immunoassays (e.g., by Western blot analysis, immunoprecipitation followed by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis, immunocytochemistry, etc.) and/or hybridization assays to detect expression of mRNAs (e.g., Northern assays, dot blots, in situ hybridization, and the like).


[0307] Prophylactic Methods


[0308] In one aspect, the invention provides a method for preventing, in a subject, a disease or condition associated with an aberrant NOVX expression or activity, by administering to the subject an agent that modulates NOVX expression or at least one NOVX activity. Subjects at risk for a disease that is caused or contributed to by aberrant NOVX expression or activity can be identified by, for example, any or a combination of diagnostic or prognostic assays as described herein. Administration of a prophylactic agent can occur prior to the manifestation of symptoms characteristic of the NOVX aberrancy, such that a disease or disorder is prevented or, alternatively, delayed in its progression. Depending upon the type of NOVX aberrancy, for example, an NOVX agonist or NOVX antagonist agent can be used for treating the subject. The appropriate agent can be determined based on screening assays described herein. The prophylactic methods of the invention are further discussed in the following subsections.


[0309] Therapeutic Methods


[0310] Another aspect of the invention pertains to methods of modulating NOVX expression or activity for therapeutic purposes. The modulatory method of the invention involves contacting a cell with an agent that modulates one or more of the activities of NOVX protein activity associated with the cell. An agent that modulates NOVX protein activity can be an agent as described herein, such as a nucleic acid or a protein, a naturally-occurring cognate ligand of an NOVX protein, a peptide, an NOVX peptidomimetic, or other small molecule. In one embodiment, the agent stimulates one or more NOVX protein activity. Examples of such stimulatory agents include active NOVX protein and a nucleic acid molecule encoding NOVX that has been introduced into the cell. In another embodiment, the agent inhibits one or more NOVX protein activity. Examples of such inhibitory agents include antisense NOVX nucleic acid molecules and anti-NOVX antibodies. These modulatory methods can be performed in vitro (e.g., by culturing the cell with the agent) or, alternatively, in vivo (e.g., by administering the agent to a subject). As such, the invention provides methods of treating an individual afflicted with a disease or disorder characterized by aberrant expression or activity of an NOVX protein or nucleic acid molecule. In one embodiment, the method involves administering an agent (e.g., an agent identified by a screening assay described herein), or combination of agents that modulates (e.g., up-regulates or down-regulates) NOVX expression or activity. In another embodiment, the method involves administering an NOVX protein or nucleic acid molecule as therapy to compensate for reduced or aberrant NOVX expression or activity.


[0311] Stimulation of NOVX activity is desirable in situations in which NOVX is abnormally downregulated and/or in which increased NOVX activity is likely to have a beneficial effect. One example of such a situation is where a subject has a disorder characterized by aberrant cell proliferation and/or differentiation (e.g., cancer or immune associated disorders). Another example of such a situation is where the subject has a gestational disease (e.g., preclampsia).


[0312] Determination of the Biological Effect of the Therapeutic


[0313] In various embodiments of the invention, suitable in vitro or in vivo assays are performed to determine the effect of a specific Therapeutic and whether its administration is indicated for treatment of the affected tissue.


[0314] In various specific embodiments, in vitro assays may be performed with representative cells of the type(s) involved in the patient's disorder, to determine if a given Therapeutic exerts the desired effect upon the cell type(s). Compounds for use in therapy may be tested in suitable animal model systems including, but not limited to rats, mice, chicken, cows, monkeys, rabbits, and the like, prior to testing in human subjects. Similarly, for in vivo testing, any of the animal model system known in the art may be used prior to administration to human subjects.


[0315] Prophylactic and Therapeutic Uses of the Compositions of the Invention


[0316] The NOVX nucleic acids and proteins of the invention are useful in potential prophylactic and therapeutic applications implicated in a variety of disorders including, but not limited to: metabolic disorders, diabetes, obesity, infectious disease, anorexia, cancer-associated cancer, neurodegenerative disorders, Alzheimer's Disease, Parkinson's Disorder, immune disorders, hematopoietic disorders, and the various dyslipidemias, metabolic disturbances associated with obesity, the metabolic syndrome X and wasting disorders associated with chronic diseases and various cancers.


[0317] As an example, a cDNA encoding the NOVX protein of the invention may be useful in gene therapy, and the protein may be useful when administered to a subject in need thereof. By way of non-limiting example, the compositions of the invention will have efficacy for treatment of patients suffering from: metabolic disorders, diabetes, obesity, infectious disease, anorexia, cancer-associated cachexia, cancer, neurodegenerative disorders, Alzheimer's Disease, Parkinson's Disorder, immune disorders, hematopoietic disorders, and the various dyslipidemias.


[0318] Both the novel nucleic acid encoding the NOVX protein, and the NOVX protein of the invention, or fragments thereof, may also be useful in diagnostic applications, wherein the presence or amount of the nucleic acid or the protein are to be assessed. A further use could be as an anti-bacterial molecule (i.e., some peptides have been found to possess anti-bacterial properties). These materials are further useful in the generation of antibodies, which immunospecifically-bind to the novel substances of the invention for use in therapeutic or diagnostic methods.


[0319] Sequence Analyses


[0320] The sequence of NOVX was derived by laboratory cloning of cDNA fragments, by in silico prediction of the sequence. cDNA fragments covering either the full length of the DNA sequence, or part of the sequence, or both, were cloned. In silico prediction was based on sequences available in CuraGen's proprietary sequence databases or in the public human sequence databases, and provided either the full length DNA sequence, or some portion thereof.


[0321] The laboratory cloning was performed using one or more of the methods summarized below:


[0322] SeqCalling™Technology: cDNA was derived from various human samples representing multiple tissue types, normal and diseased states, physiological states, and developmental states from different donors. Samples were obtained as whole tissue, primary cells or tissue cultured primary cells or cell lines. Cells and cell lines may have been treated with biological or chemical agents that regulate gene expression, for example, growth factors, chemokines or steroids. The cDNA thus derived was then sequenced using CuraGen Corporation's SeqCalling technology which is disclosed in full in U.S. Ser. No. 09/417,386 filed Oct. 13, 1999, and Ser. No. 09/614,505 filed Jul. 11, 2000. Sequence traces were evaluated manually and edited for corrections if appropriate. cDNA sequences from all samples were assembled together, sometimes including public human sequences, using bioinformatics programs to produce a consensus sequence for each assembly. Each assembly is included in CuraGen Corporation's database. Sequences were included as components for assembly when the extent of identity with another component was at least 95% over 50 bp. Each assembly represents a gene or portion thereof and includes information on variants, such as splice forms single nucleotide polymorphisms (SNPs), insertions, deletions and other sequence variations.


[0323] Variant sequences are also included in this application. A variant sequence can include a single nucleotide polymorphism (SNP). A SNP can, in some instances, be referred to as a “cSNP” to denote that the nucleotide sequence containing the SNP originates as a cDNA. A SNP can arise in several ways. For example, a SNP may be due to a substitution of one nucleotide for another at the polymorphic site. Such a substitution can be either a transition or a transversion. A SNP can also arise from a deletion of a nucleotide or an insertion of a nucleotide, relative to a reference allele. In this case, the polymorphic site is a site at which one allele bears a gap with respect to a particular nucleotide in another allele. SNPs occurring within genes may result in an alteration of the amino acid encoded by the gene at the position of the SNP. Intragenic SNPs may also be silent, when a codon including a SNP encodes the same amino acid as a result of the redundancy of the genetic code. SNPs occurring outside the region of a gene, or in an intron within a gene, do not result in changes in any amino acid sequence of a protein but may result in altered regulation of the expression pattern. Examples include alteration in temporal expression, physiological response regulation, cell type expression regulation, intensity of expression, and stability of transcribed message.


[0324] Presented information includes that associated with genomic clones, public genes and ESTs sharing sequence identity with the disclosed sequence and CuraGen Corporation's Electronic Northern bioinformatic tool.







EXAMPLES


Example A


Sequence related information

[0325] The NOV1 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 1A.
2TABLE 1ANOV1 Sequence AnalysisSEQ ID NO:1711 bpNOV1a,TGCAGAATGAACCAAGGAGACTCAAACCCAGCAGCTACTCCGCATGCGGCAGAAGACACG582522-01 DNA SequenceTTCAAGGAGATGACAGATGGATGTGTCAGCACAACAGATTTGTTTTGGACTGTAAAGACAAACAGCCTGATGTACCATTTGCGGGAGGCTCCGTGGTGCAGTTACTGCAGCCATATGAGATATGGCGAGAGCTTTTTTCCCCACTTCATGCACTGAATTTTGGAACTGGGGGAGATACAACAAGACATGTTTTGTGGAGACTAAAGAGCGGAGAACTGGGGAATACTAAGCCTAAGGTCATTGTTTTCTGGCTAGGAAGAAACAACCATGAAAATATGGCAGAAGAGGTAGCAGGTGGTATGGCGGCCATCGTACAACTTATCAACACAAGGCAGCCACAGGCCAAAATCATTGTATTTGATCTGTTACCTCAAGGTGAGAAACCCAACCCTTTGAGGCAAAAGAACGCCAAGGTGAACCCACTCGTCAAGATTTCGCTGCTGAAACTTACCAACGTGCAGCTCCTGGATACTGACAGGGGTTTCGTGCACTCCGACCGTGCCATCTCCTGCCACGACATGTTTGATTTTCTGCATTTGACAGGAGGTGGCTACTCAAAGGTCTGCAAACCCTTGAATGAACTGATCATGCAGTTGTTGGAGGAAACACCTGAGGAGAAACAAACCACCATTGCCTGACTGGCTCCCATGAGTORF STart: ATG at 7ORF Stop: TGA at 694SEQ ID NO:2229 aaMW at 25656.2 kDNOV1a,MNQGDSNPAATPHAAEDIQGDDRWMCQHNRFVLDCKDKQPDVPFAGGSVVQLLQPYEICG58522-01 Protein SequenceWRELFSPLHALNFGTGGDTTRHVLWRLKSGELGNTKPKVIVFWLGRNMAEEVAGGMAAIVQLINTRQPQAKIIVFDLLPQGEKPNPLRQKNAKVNPLVKISLLKLTNVQLLDTDRGFVHSDRAISCHDMFDELHLTGGGYSKVCKPLNELIMQLLEETPEEEQTTIA


[0326] Further analysis of the NOV1a protein yielded the following properties shown in Table 1B.
3TABLE 1BProtein Sequence Properties NOV1aPsort0.6500 probability located in cytoplasm; 0.2340 probabilityanalysis:located in lysosome (lumen); 0.1000 probability located inmitochondrial matrix space; 0.0000 probability located inendoplasmic reticulum (membrane)SignalPNo Known Signal Sequence Predictedanalysis:


[0327] A search of the NOV1a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 1C.
4TABLE 1CGeneseq Results for NOV1aIdentities/NOV1aSimilaritesResidues/for theGeneseqProtein/Organism/LengthMatchMatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAB49433Human beta platelet1 . . . 229196/229 e−114activating factor1 . . . 229(85%)acetylhydrolase - Homo209/229sapiens, 229 aa. [U.S.(90%)Pat. No. 6146868-A,14 NOV. 2000]AAB49432Rat beta platelet1 . . . 229195/229 e−114activating factor1 . . . 229(85%)acetylhydrolase - Rattus208/229norvegicus, 229 aa. [U.S.(90%)Pat. No. 6146868-A,14 NOV. 2000]AAB49434Murine beta platelet1 . . . 229192/229 e−111activating factor1 . . . 229(83%)acetylhydrolase - Mus205/229musculus, 229 aa. [U.S.(88%)Pat. No. 6146868-A,14 NOV. 2000]AAB49436Bovine gamma platelet4 . . . 219124/2165e−74activating factor3 . . . 218(57%)acetylhydrolase - Bos165/216taurus, 1232 aa. [U.S.(75%)Pat. No. 6146868-A,14 NOV. 2000]AAB49435Human gamma platelet4 . . . 219124/2162e−73activating factor3 . . . 218(57%)acetylhydrolase - Homo164/216sapiens, 231 aa. [U.S.(75%)Pat. No. 6146868-A,14 NOV. 2000]


[0328] In a BLAST search of public sequence databases, the NOV1a protein was found to have homology to the proteins shown in the BLASTP data in Table 1D.
5TABLE 1DPublic BLASTP Results for NOV1aNOV1aIdentities/ProteinResidues/Similarities forAccessionProtein/Organism/Matchthe MatchedExpectNumberLengthResiduesPortionValueQ29459Platelet-activating1 . . . 229196/229 (85%) e−114factor acetylhydrolase1 . . . 229209/229 (90%)IB beta subunit(EC 3.1.1.47) (PAFacetylhydrolase 30kDa subunit)(PAF-AH 30 kDasubunit) (PAF-AHbeta subunit)(PAFAH betasubunit) - Homosapiens (Human),and, 229 aa.O35264Platelet-activating1 . . . 229195/229 (85%) e−113factor acetylhydrolase1 . . . 229208/229 (90%)IB beta subunit (EC3.1.1.47) (PAFacetylhydrolase 30kDa subunit)(PAF-AH betasubunit) (PAFAHbeta subunit)(Platelet-activating factoracetylhydrolase alpha,2 subunit) (PAF-AHalpha 2) - Rattusnorvegicus (Rat),229 aa.Q61206Platelet-activating1 . . . 229192/229 (83%) e−111factor acetylhydrolase1 . . . 229205/229 (88%)IB beta subunit (EC3.1.1.47) (PAFacetylhydrolase 30kDa subunit)(PAF-AH 30 kDasubunit) (PAF-AHbeta subunit)(PAFAH betasubunit) - Musmusculus (Mouse),229 aa.Q29460Platelet-activating4 . . . 219125/216 (57%)8e−74factor acetylhydrolase3 . . . 218165/216 (75%)IB gamma subunit(EC 3.1.1.47)(PAF acetylhydrolase29 kDa subunit)(PAF-AH 29 kDasubunit) (PAF-AHgamma subunit)(PAFAH gammasubunit) - Bos taurus(Bovine), 232 aa.Q15102Platelet-activating4 . . . 219124/216 (57%)7e−73factor acetyl-3 . . . 218164/216 (75%)hydrolase IBgamma subunit(EC 3.1.1.47)(PAF acetylhydrolase29 kDa subunit)(PAF-AH 29 kDasubunit) (PAF-AHgamma subunit)(PAFAH gammasubunit) - Homosapiens (Human),231 aa.


[0329] PFam analysis predicts that the NOV1a protein contains the domains shown in the Table 1E.
6TABLE 1EDomain Analysis of NOV1aNOV1aIdentities/SimilaritiesExpectPfam DomainMatch Regionfor the Matched RegionValuePAF-AH:7 . . . 221150/215 (70%)6e−147domain 1 of 1186/215 (87%)



Example 2

[0330] The NOV2 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 2A.
7TABLE 2ANOV2 Sequence AnalysisSEQ ID NO:31457 bpNOV2a,CGATTCCGATGGGTCCTTTGAAAGCTTTTCTCTTCTCCCCTTTTCTTCTGCGGAGTCACG58520-01 DNA SequenceAAGTAGAGGGGTGAGGTTGGTCTTCTTGTTACTGACCCTGCATTTGGGAAACGTTGATAAGGCAGATGATGAAGATGATGAGGATTTAACGGTGAACAAAACCTGGGTCTTGGCCCCAAAAATTCATGAAGGAGATATCACACAAATTCTGAATTCATTGCTTCAAGGCTATGACAATAAACTTCGTCCAGATATAGGAGTGAGGCCCACAGTAATTGAAACTGATGTTTATGTAAACAGCATTGGACCAGTTGATCCAATTAATATGGAATATACAATAGATATAATTTTTGCCCAAACCTGGTTTGACAGTCGTTTAAAATTCAATAGTACCATGAAAGTGCTTATGCTTAACAGTAATATGGTTGGAAAAATTTGGATTCCTGACACTTTCTTCAGAAACTCAAGAAAATCTGATGCTCACTGGATAACAACTCCTAATCGTCTGCTTCGAATTTGGAATGATAGATGGATACCCTAAAAATGAAATTGAGTTATCAATGGAAGCGAAGTTCTGTGGAAGTGGGCGACACAAGATCCGGAGATTATATCAGTTTGCATTTGTAGGGTTACGGAACTCAACTGAAATCACTCACACGATCTCTGGGGATTATGTTATCATGACAATTTTTTTTGACCTGAGCAGAAGAATGGGATATTTCACTATTCAGACCTACATTCCATGCATTCTGACAGTTGTTCTTTCTTGGGTGTCTTTTTGGATCAATAAAGATGCAGTGCCTGCAAGAACATCGTTGGGTATGACATCTATAGGTATCACTACAGTTCTGACTATGACAACCCTGAGTACAATTGCCAGGAAGTCTTTACCTAAGGTTTCTTATGTGACTGCGATGGATCTCTTTGTTTCTGTTTGTTTCATTTTTGTTTTTGCAGCCTTGATGGAATATGGAACCTTGCATTATTTTACCAGCAACCAAAAAGGAAAGACTGCTACTAAAGACAGAAAGCTAAAAAATAAAGCCTCGACTCCTGGTCTCCATCCTGGATCCACTCTGATTCCAATGAATAATATTTCTGTGCCGCAAGAAGATGATTATGGGTATCAGTGTTTGGAGGGCAAAGATTGTGCCAGCTTCTTCTGTTGCTTTGAAGACTGCAGAACAGGATCTTGGAGGGAAGGAAGGATACACATACGCATTGCCAAAATTGACTCTTATTCTAGAATATTTTTCCCAACCGCTTTTGCCCTGTTCAACTTGGTTTATTGGGTTGGCTATCTTTACTTATAAAATCTACTTCATAAGCAAAAATCAAAAGAAORF Start: ATG at 9ORF Stop: TAA at 1425SEQ ID NO:4472 aaMW at 54100.9 kDNOV2a,MGPLKAFLFSPELLRSQSRGVRLVFLLLTLHLGNVDKADDEDDEDLTVNKTWVLAPKICG58520-01 Protein SequenceHEGDITQILNSLLQGYDNKLRPDIGVRPTVIETDVYVNSIGPVDPINMEYTIDIIFAQTWFDSRLKFNSTMKVLMLNSNMVGKIWIPDTFFRNSRKSDAHWITTPNRLLRIWNDGRVLYTLRRLTINAECYLQLHNFPMDEHSCPLEFSSFSIDGYPKNEIELSMEAKFCGSGRHKIRRLYQFAFVGLRNSTEITHTISGDYVIMTIFFDLSRRMGYFTIQTYIPCILTVVLSWVSFWINKDAVPARTSLGMTSIGITTVLTMTTLSTIARKSLPKVSYVTAMDLFVSVCFIFVFAALMEYGTLHYFTSNQKGKTATKDRKLKNKASTPGLHPGSTLIPMNNISVPQEDDYGYQCLEGKDCASFFCCFEDCRTGSWREGRIHIRIAKIDSYSRIFFPTAFALFNLVYWVGYLYLSEQ ID NO:51521 bpNOV2b,CAACCAAGAGGCAAGAGGCGAGAGAAGGAAAAAAAAAAAAGCGATGAGTTCGCCAAATCG58520-02 DNA SequenceATATGGAGCACAGGAAGCTCAGTCTACTCGACTCCTGTATTTTCACAGAAAATGACGGTGTGGATTCTGCTCCTGCTGTCGCTCTACCCTGGCTTCACTAGCCAGAAATCTGATGATGACTATGAAGATTATGCTTCTAACAAAACATGGGTCTTGACTCCAAAAGTTCCTGAGGGTGATGTCACTGTCATCTTAAACAACCTGCTGGAAGGATATGACAATAAACTTCGGCCTGATATAGGAGTGAAGCCAACGTTAATTCACACAGACATGTATGTGAATAGCATTGGTCCAGTGAACGCTATCAATATGGAATACACTATTGATATATTTTTTGCGCAAACGTGGTATGACAGACGTTTGAAATTTAACAGCACCATTAAAGTCCTCCGATTGAACAGCAACATGGTGGGGAAAATCTGGATTCCAGACACTTTCTTCAGAAATTCCAAAAAAGCTGATGCACACTGGATCACCACCCCCAACAGGATGCTGAGAATTTGGAATGATGGTCGAGTGCTCTACACCCTAAGGTTGACAATTGATGCTGAGTGCCAATTACAATTGCACAACTTTCCAATGGATGAACACTCCTGCCCCTTGGAGTTCTCCAGTTATGGCTATCCACGTGAAGAAATTGTTTATCAATGGAAGCGAAGTTCTGTTGAAGTGGGCGACACAAGATCCTGGAGGCTTTATCAATTCTCATTTGTTGGTCTAAGAAATACCACCGAAGTAGTGAAGACAACTTCCGGAGATTATGTGGTCATGTCTGTCTACTTTGATCTGAGCAGAAGAATGGGATACTTTACCATCCAGACCTATATCCCCTGCACACTCATTGTCGTCCTATCCTGGGTGTCTTTCTGGATCAATAAGGATGCTGTTCCAGCCAGAACATCTTTAGGTATCACCACTGTCCTGACAATGACCACCCTCAGCACCATTGCCCGGAAATCGCTCCCCAAGGTCTCCTATGTCACAGCGATGGATCTCTTTGTATCTGTTTGTTTCATCTTTGTCTTCTCTGCTCTGGTGGAGTATGGCACCTTGCATTATTTTGTCAGCAACCGGAAACCAAGCAAGGACAAAGATAAAAAGAAGAAAAACCCTCTTCTTCGGATGTTTTCCTTCAAGGCCCCTACCATTGATATCCGCCCAAGATCAGCAACCATTCAAATGAATAATGCTACACACCTTCAAGAGAGAGATGAAGAGTACGGCTATGAGTGTCTGGACGGCAAGGACTGTGCCAGTTTTTTCTGCTGTTTTGAAGATTGTCGAACAGGAGCTTGGAGACATGGGAGGATACATATCCGCATTGCCAAAATGGACTCCTATGCTCGGATCTTCTTCCCCACTGCCTTCTGCCTGTTTAATCTGGTCTATTGGGTCTCCTACCTCTACCTGTGAGGAGGTATGGGTTTTACTGATATGGTTCTTATTCACTGAGTCTCATGGAGORF Start ATG at 44ORF Stop: TGA at 1469SEQ ID NO:6475 aaMW at 55184.9 kDNOV2b,MSSPNIWSTGSSVYSTPVFSQKMTVWILLLLSLYPGFTSQKSDDDYEDYASNKTWVLTCG58520-02 Protein SequencePKVPEGDVTVILNNLLEGYDNKLRPDIGVKPTLIHTDMYVNSIGPVNAINMEYTIDIFFAQTWYDRRLKFNSTIKVLRLNSNMVGKIWIPDTFFRNSKKADAHWITTPNRMLRIWNDGRVLYTLRLTIDAECQLQLHNFPMDEHSCPLEFSSYGYPREEIVYQWKRSSVEVGDTRSWRLYQFSFVGLRNTTEVVKTTSGDYVVMSVYFDLSRRMGYFTIQTYIPCTLIVVLSWVSFWINKDAVPARTSLGITTVLTMTTLSTIARKSLPKVSYVTAMDLFVSVCFIFVFSALVEYGTLHYFVSNRKPSKDKDKKKKNPLLRMFSFKAPTIDIRPRSATIQMNNATHLQERDEEYGYECLDGKDCASFFCCFEDCRTGAWRHGRIHIRIAKMDSYARIFFPTAFCLFNLVYWVSYLYLSEQ ID NO:71455 bpNOV2c,TAGTGCAGCACACGTAAAAAAGCGATTCCGATGGGTCCTTTGAAAGCTTTTCTCTTCTCG58520-03 DNA SequenceCCCCTTTTCTTCTGCGGAGTCAAAGTAGAGGGGTGAGGTTGGTCTTCTTGTTACTGACCCTGCATTTGGGAAACTGGGTTGATAAGGCAGATGATGAAGATGATGAGGATTTAACGGTGAACAAAACCTGGGTCTTGGCCCCAAAAATTCATGAAGGAGATATCACACAAATTCTGAATTCATTGCTTCAAGGCTATGACAATAAACTTCGTCCAGATATAGGAGTGAGGCCCACAGTAATTGAAACTGATGTTTATGTAAACAGCATTGGACCAGTTGATCCAATTAATATGGAATATACAATAGATATAATTTTTGCCCAAACCTGGTTTGACAGTCGTTTAAAATTCAATAGTACCATGAAAGTGCTTATGCTTAACAGTAATATGGTTGGAAAAATTTGGATTCCTGACACTTTCTTCAGAAACTCAAGAAAATCTGATGCTCACTGGATAACAACTCCTAATCGTCTGCTTCGAATTTGGAATGATGGACGAGTTCTGTATACTCTAAGGTTGACAATTAATGCAGAATGTTATCTTCAGCTTCATAACTTTCCCATGGATGAACATTCCTGTCCACTGGAATTTTCAAGCGATGGATACCCTAAAAATGAAATTGAGTATAAGTGGAAAAAGCCCTCCGTAGAAGTGGCTGATCCTAAATACTGGAGATTATATCAGTTTGCATTTGTAGGGTTACGGAACTCAACTGAAATCACTCACACGATCTCTGGTGATTATGTTATCATGACAATTTTTTTTGACCTGAGCAGAAGAATGGGATATTTCACTATTCAGACCTACATTCCATGCATTCTGACAGTTGTTCTTTCTTGGGTGTCTTTTTGGATCAATAAAGATGCAGTGCCTGCAAGAACATCGTTGGGTATCACTACAGTTCTGACTATGACAACCCTGAGTACAATTGCCAGGAAGTCTTTACCTAAGGTTTCTTATGTGACTGCGATGGATCTCTTTGTTTCTGTTTGTTTCATTTTTGTTTTTGCAGCCTTGATGGAATATGGAACCTTGCATTATTTTACCAGCAACCAAAAAGGAAAGACTGCTACTAAAGACAGAAAGCTAAAAAATAAAGCCTCGGTAACTCCTGGTCTCCATCCTGGATCCACTCTGATTCCAATGAATAATATTTCTGTGCCGCAAGAAGATGATTATGGGTATCAGTGTTTGGAGGGCAAAGATTGTGCCAGCTTCTTCTGTTGCTTTGAAGACTGCAGAACAGGATCTTGGAGGGAAGGAAGGATACACATACGCATTGCCAAAATTGACTCTTATTCTAGAATATTTTTCCCAACCGCTTTTGCCCTGTTCAACTTGGTTTATTGGGTTGGCTATCTTTTACTTATAAAATCTACTTCATAAGCAAAAATCAAAAORF Start: ATG at 31ORF Stop: TAA at 1426SEQ ID NO:8465 aaMW at 53597.3 kDNOV2c,MGPLKAFLFSPFLLRSQSRGVRLVFLLLTLHLGNWVDKADDEDDEDLTVNKTWVLAPKCG58520-03 Protein SequenceIHEGDITQILNSLLQGYDNKLRPDIGVRPTVIETDVYVNSIGPVDPINMEYTIDIIFAQTWFDSRLKFNSTMKVLMLNSNMVGKIWIPDTFFRNSRKSDAHWITTPNRLLRIWNDGRVLYTLRLTINAECYLQLHNFPMDEHSCPLEFSSDGYPKNEIEYKWKKPSVEVADPKYWRLYQFAFVGLRNSTEITHTISGDYVIMTIFFDLSRRMGYFTIQTYIPCILTVVLSWVSFWINKDAVPARTSLGITTVLTMTTLSTIARKSLPKVSYVTAMDLFVSVCFIFVFAALMEYGTLHYFTSNQKGKTATKDRKLKNKASVTPGLHPGSTLIPMNNISVPQEDDYGYQCLEGKDCASFFCCFEDCRTGSWREGRIHIRIAKIDSYSRIFFPTAFALFNLVYWVGYLYL


[0331] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 2B.
8TABLE 2BComparison of NOV2a against NOV2b through NOV2c.ProteinNOV2a Residues/Identities/SequenceMatch ResiduesSimilarities for the Matched RegionNOV2b24 . . . 472311/458 (67%)27 . . . 475352/458 (75%)NOV2c 1 . . . 472414/474 (87%) 1 . . . 465415/474 (87%)


[0332] Further analysis of the NOV2a protein yielded the following properties shown in Table 2C.
9TABLE 2CProtein Sequence Properties NOV2aPsort0.6400 probability located in plasma membrane; 0.4600analysis:probability located in Golgi body; 0.3700 probability locatedin endoplasmic reticulum (membrane); 0.1000 probabilitylocated in endoplasmic reticulum (lumen)SignalPLikely cleavage site between residues 38 and 39analysis:


[0333] A search of the NOV2a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 2D.
10TABLE 2DGeneseq Results for NOV2aIdentities/NOV2aSimilaritesProtein/Residues/for theGeneseqOrganism/LengthMatchMatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAM41007Human polypeptide24 . . . 472334/4510.0SEQ ID NO 5938 -49 . . . 489(74%)Homo sapiens, 489 aa.379/451[WO200153312-A1,(83%)26 JUL. 2001]AAM39221Human polypeptide24 . . . 472334/4510.0SEQ ID NO 2366(74%)Homo sapiens, 467 aa.27 . . . 467379/451[WO200153312-A1,(83%)26 JUL. 2001]AAR83968GABA-A receptor24 . . . 472300/472e−169gamma-3 subunit - 5 . . . 467(63%)Homo sapiens, 467 aa.356/472[WO9529234-A1,(74%)02 NOV. 1995]AAW59048GABA-A receptor62 . . . 472193/448e−102epsilon sub-unit70 . . . 506(43%)related protein -274/448Mammalia, 506 aa.(61%)[DE19644501-A1,30 APR. 1998]AAW61045Human GABA62 . . . 472193/448e−102receptor epsilon70 . . . 506(43%)subunit - Homo274/448sapiens, 506 aa.(61%)[WO9823742-A1,04 JUN. 1998]


[0334] In a BLAST search of public sequence databases, the NOV2a protein was found to have homology to the proteins shown in the BLASTP data in Table 2E.
11TABLE 2EPublic BLASTP Results for NOV2aNOV2aIdentities/ProteinResidues/Similarities forAccessionProtein/Organism/Matchthe MatchedExpectNumberLengthResiduesPortionValueP23574Gamma-amino- 1 . . . 472426/475 (89%)0.0butyric-acid 1 . . . 465440/475 (91%)receptor gamma-1subunit precursor(GABA(A)receptor) -Rattus norvegicus(Rat), 465 aa.Q9R0Y8Gamma-amino- 1 . . . 472420/477 (88%)0.0butyric-acid 1 . . . 465434/477 (90%)receptor gamma-1subunit precursor(GABA(A)receptor) -Mus musculus(Mouse), 465 aa.JH0824gamma-amino-16 . . . 472390/463 (84%)0.0butyric acid A12 . . . 464416/463 (89%)receptor gamma 1chain precursor -chicken, 464 aa.JH0316gamma-amino-24 . . . 472336/451 (74%)0.0butyric acid A26 . . . 466380/451 (83%)receptor gamma 2chain alternativelyspliced precursor -mouse, 466 aa.P18508Gamma-amino-24 . . . 472335/451 (74%)0.0butyric-acid receptor26 . . . 466379/451 (83%)gamma-2 subnuitprecursor(GABA(A)receptor) -Rattus norvegicus(Rat), 466 aa.


[0335] PFam analysis predicts that the NOV2a protein contains the domains shown in the Table 2F.
12TABLE 2FDomain Analysis of NOV2aNOV2aMatchIdentities/SimilaritiesExpectPfam DomainRegionfor the Matched RegionValueNeur_chan_LBD: 63 . . . 273 66/271 (24%)2.7e−56domain 1 of 1162/271 (60%)Cys-protease-3C:363 . . . 369 4/7 (57%)5.2domain 1 of 1 6/7 (86%)Neur_chan_memb:280 . . . 466 44/297 (15%)1.2e−60domain 1 of 1164/297 (55%)



Example 3

[0336] The NOV3 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 3A.
13TABLE 3ANOV3 Sequence AnalysisSEQ ID NO:91440 bpNOV3a,GAAGAGATGGTCCTGGCTTTCCAGTTAGTCTCCTTCACCTACATCTGGATCATATTGACG58518-01 DNA SequenceAACCAAATGTTTGTGCTGCTTCTAACATCAAGATGACACACCAGCGGTGCTCCTCTTCAATGAAACAAACCTGGAAACAAGAAACTAGAATGAAGAAAGATGACAGTACCAAAGCGCGGCCTCAGAAATATGAGCAACTTCTCCATATAGAGGACAACGATTTCGCAATGAGACCTGGATTTGGAGGTGAGTATTATCCTCTCAAAATTGGGTCTCCAGTGCCAGTAGGTATAGATGTCCATGTTGAAAGCATTGACAGCATTTCAGAGACTAACATGGTAAGTTTCTTCATGGGATATGACTTTACAATGACTTTTTATCTCAGGCATTACTGGAAAGACGAGAGGCTCTCCTTTCCTAGCACAGCAAACAAAAGCATGACATTTGATCATAGATTGACCAGAAAGATCTGGGTGCCTGATATCTTTTTTGTCCACTCTAAAAGATCCTTCATCCATGATACAACTATGGAGAATATCATGCTGCGCGTACACCCTGATGGAAACGTCCTCCTAAGTCTCAGGAGGATAACGGTTTCGGCCATGTGCTTTATGGATTTCAGCAGGTTTCCTCTTGACACTCAAAATTGTTCTCTTGAACTGGAAAGCGCCTACAATGAGGATGACCTAATGCTATACTGGAAACACGGAAACAAGTCCTTAAATACTGAAGAACATATGTCCCTTTCTCAGTTCTTCATTGAAGACTTCAGTGCATCTAGTGGATTAGCTTTCTATAGCAGCACAGGTTGGTACAATAGGCTTTTCATCAACTTTGTGCTAAGGAGGCATGTTTTCTTCTTTGTGCTGCAAACCTATTTCCCAGCCATATTGATGGTGATGCTTTCATGGGTTTCATTTTGGATTGACCGAAGAGCTGTTCCTGCAAGAGTTTCCCTGGGTGGAATCACCACAGTGCTGACCATGTCCACAATCATCACTGCTGTGAGCGCCTCCATGCCCCAGGTGTCCTACCTCAAGGCTGTGGATGTGTACCTGTGGGTCAGCTCCCTCTTTGTGTTCCTGTCAGTCATTGAGTATGCAGCTGTGAACTACCTCACCACAGTGGAAGAGCGGAAACAATTCAAGAAGACAGGAAAGGTACAGATTTCTAGGATGTACAATATTGATGCAGTTCAAGCTATGGCCTTTGATGGTTGTTACCATGACAGCGAGATTGACATGGACCAGACTTCCCTCTCTCTAAACTCAGAAGACTTCATGAGAAGAAAATCGATATGCAGCCCCAGCACCGATTCATCTCGGATAAAGAGAAGAAAATCCCTAGGAGGACATGTTGGTAGAATCATTCTGGAAAACAACCATGTCATTGACACCTATTCTAGGATTTTATTCCCCATTGTGTATATCTTTATTTAATTTORF Start: ATG at 7ORF Stop: TAA at 1435SEQ ID NO:10476 aaMW at 55285.2 kDNOV3a,MVLAFQLVSFTYIWIILKPNVCAASNIKMTHQRCSSSMKQTWKQETRMKKDDSTKARPCG58518-01 Protein SequenceQKYEQLLHIEDNDFAMRPGFGGEYYPLKIGSPVPVGIDVHVESIDSISETNMVSFFMGYDFIMTFYLRHYWKDERLSFPSTANKSMTFDHRLTRKIWVPDIFFVHSKRSFIHDTTMENIMLRVHPDGNVLLSLRRITVSAMCFMDFSRFPLDTQNCSLELESAYNEDDLMLYWKHGNKSLNTEEHMSLSQFFIEDFSASSGLAFYSSTGWYNRLFINFVLRRHVFFFVLQTYFPAILMVMLSWVSFWIDRRAVPARVSLGGITTVLTMSTIITAVSASMPQVSYLKAVDVYLWVSSLFVFLSVIEYAAVNYLTTVEERKQFKKTGKVQISRMYNIDAVQAMAFDGCYHDSEIDMDQTSLSLNSEDFMRRKSICSPSTDSSRIKRRKSLGGHVGRIILENNHVIDTYSRILFPIVYIFI


[0337] Further analysis of the NOV3a protein yielded the following properties shown in Table 3B.
14TABLE 3BProtein Sequence Properties NOV3aPSort0.6850 probability located in endoplasmic reticulumanalysis:(membrane); 0.6400 probability located in plasma membrane;0.4600 probability located in Golgi body; 0.2400 probabilitylocated in nucleusSignalPLikely cleavage site between residues 25 and 26analysis:


[0338] A search of the NOV3a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 3C.
15TABLE 3CGeneseq Results for NOV3aIdentities/NOV3aSimilaritesProtein/Residues/for theGeneseqOrganism/LengthMatchMatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAU04467Human gamma-amino 1 . . . 474454/4750.0butyric acid (GABA) 1 . . . 456(95%)receptor protein #1 -454/475Homo sapiens, 467 aa.(95%)[WO200153489-A1,26 JUL. 2001]AAU04470Human gamma-amino48 . . . 474408/4280.0butyric acid (GABA) 1 . . . 409(95%)receptor protein #4 -408/428Homo sapiens, 420 aa.(95%)[WO200153489-A1,26 JUL. 2001]AAU04468Human gamma-amino 1 . . . 393370/3940.0butyric acid (GABA) 1 . . . 377(93%)receptor protein #2370/394Homo sapiens, 392 aa.(93%)[WO200153489-A1,26 JUL. 2001]AAU04471Human gamma-amino48 . . . 393324/347e−180butyric acid (GABA) 1 . . . 330(93%)receptor protein #5 -(93%)[WO200153489-A1,26 JUL. 2001]AAU04469Human gamma-amino 1 . . . 192176/1922e−96butyric acid (GABA) 1 . . . 177(91%)receptor protein #3 -176/192Homo sapiens, 180 aa.(91%)[WO200153489-A1,26 JUL. 2001]


[0339] In a BLAST search of public sequence databases, the NOV3a protein was found to have homology to the proteins shown in the BLASTP data in Table 3D.
16TABLE 3DPublic BLASTP Results for NOV3aNOV3aIdentities/ProteinResidues/Similarities forAccessionProtein/Organism/Matchthe MatchedExpectNumberLengthResiduesPortionValueP50573Gamma-amino- 1 . . . 474383/476 (80%)0.0butyric-acid 1 . . . 453407/476 (85%)receptor rho-3subunit precursor(GABA(A)receptor) - Rattusnorvegicus (Rat),464 aa.Q9YGQ2GAMMA-AMINO- 1 . . . 474293/485 (60%)e−153BUTYRIC-ACID 4 . . . 459363/485 (74%)RECEPTOR RHO-3SUBUNIT - Moroneamericana(White perch),470 aa.P50572Gamma-amino-49 . . . 474270/427 (63%)e−144butyric-acid58 . . . 463317/427 (74%)receptor rho-1subunit precursor(GABA(A)receptor) - Rattusnorvegicus (Rat),474 aa.P56475Gamma-amino-49 . . . 474270/427 (63%)e−143butyric-acid58 . . . 463317/427 (74%)receptor rho-1subunit precursor(GABA(A)receptor) - Musmusculus (Mouse),474 aa.P24046Gamma-amino-49 . . . 474268/427 (62%)e−143butyric-acid57 . . . 462317/427 (73%)receptor rho-1subunit precursor(GABA(A)receptor) -Homo sapiens(Human), 473 aa.


[0340] PFam analysis predicts that the NOV3a protein contains the domains shown in the Table 3E.
17TABLE 3EDomain Analysis of NOV3aNOV3aMatchIdentities/SimilaritiesExpectPfam DomainRegionfor the Matched RegionValueNeur_chan_LBD: 88 . . . 282 70/250 (28%)1.2e−54domain 1 of 1165/250 (66%)Neur_chan_memb:289 . . . 475 44/292 (15%)7.6e−28domain 1 of 1141/292(48%)



Example 4

[0341] The NOV4 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 4A.
18TABLE 4ANOV4 Sequence AnalysisSEQ ID NO:111587 bpNOV4a,GAACAGAAATGAATAAAAGTCGCTGGCAGAGTAGAAGACGACATGGGAGAAGAAGCCACG58516-01 DNA SequenceCCAGCAGAACCCTTGGTTCAGACTCCGTGATTCTGAAGACAGGTCTGACTCCCGGGCAGCACAGCCCGCTCACGATTCCGGCCACGGTGATGACGAGTCTCCGTCAACCTCGTCTGGCACAGCTGGGACCTCCTCTGTGCCAGAGCTACCTGGGTTTTACTTTGACCCTGAAAAGAAACGCTACTTCCGCTTGCTCCCTGGACATAACAACTGCAACCCCCTGACGAAAGAGAGCATCCGGCAGAAGGAGATGGAGAGCAAGAGACTGCGGCTGCTCCAGGAAGAAGACAGACGGAAAAAGATTGCCAGGATGGGATTTAATGCATCTTCCATGCTACGAAAAAGCCAGCTGGGTTTTCTCAACGTCACCAATTACTGCCATTTAGCCCACGAGCTGCGTCTCAGCTGCATGGAGAGGAAAAAGGTCCAGATTCGAAGCATGGATCCCTCCGCCTTGGCAAGCGACCGATTTAACCTCATACTGGCAGATACCAACAGTGACCGGCTCTTCACAGTGAACGATGTTACAGTTGGAGGCTCCAAGTATGGTATCATCAACCTGCAAGTCTGAAGACCCCTACGCTCAAGGTGTTCATGCCACGAAAACCTCCGATTCTCACCAACCGGAAGGTGAACACTTCGGTGTGCTGGGCCTCGCTGAATCACTTGGATTCCCACATTCTGCTATGCCTCATGGGACTCGCAGAGACTCCAGGCTGTGCCACCCTGCTCCCAGCATCACTGTTCGTCAATAGTCCCCACCCAGGAATAGACCGGCCTGGCATGCTCTGCAGTTTCCGGATCCCTGGGGGTGCCTGGTCCTGTGCCTGGTCCCTGAATATCCAAGCAAATAACTGCTTCAGTACAGGCTTGTCTCGGCGGGTCCTGTTGACCAACGTGGTGACGGGACACCGGCAGTCCTTTGGGACCAACAGTGATGTCTTGGCCCAGCAGTTTGCTCTCATGGCTCCTCTGCTGTTTAATGGCTGCCGCTCTGGGGAAATCTTTGCCATTGATCTGCGTTGTGGAAATCAAGGCAAGGGATGGAAGGCCACCCGCCTGTTTCATGATTCAGCAGTGACCTCTGTGCGGATCCTCCAAGATGAGCAATACCTGATGGCTTCAGACATGGCTGGAAAGATCAAGCTGTGGGACCTGAGGACCACGAAGTGCGTAAGGCAGTACGAAGGCCACGTGAATGAGTACGCCTACCTGCCCCTGCATGTGCACGAGGAAGAAGGAATCCTGGTGGCAGTGGGCCAGGACTGCTACACGAGAATCTGGAGCCTCCACGATGCCCGCCTACTGAGAACCATACCCTCCCCGTACCCTGCCTCCAAGGCCGACATTCCCAGTGTGGCCTTCTCGTCGCGGCTGGGGGGCTCCCGGGGAGAATCTGGAGCCTCCACGATGCCCGCCTACTGAGAACCATACCCTCCCCGTACCCTGCCTCCAAGGCCGACATTCCCAGTGTGGCCTTCTCGTCGCGGCTGGGGGGCTCCCGGGGGCGCGCCGGGGCTGCTCATGGCTGTCGGGCAGGACCTTTACTGTTACTCCTACAGCTAATTCTGCAGGGCACAGCCCAGAGCCATGTGGATTTGACTTACGGGAGTAAAGCGTAACTTTTTACTGCATCTAATGAGGORF Start: ATG at 9ORF Stop: TAA at 1563SEQ ID NO:12518 aaMW at 57769.3 kDNOV4a,MNKSRWQSRRHGRRSHQQNPWFRLRDSEDRSDSRAAQPAHDSGHGDDESPSTSSGTACG58516-01 Protein SequenceGTSSVPELPGFYFDPEKKRYFRLLPGENNCNPLTKESIRQKEMESKRLRLLQEEDRRKKIARMGFNASSMLRKSQLGFLNVTNYCHLAHELRLSCMERKKVQIRSMDPSALASDRFNLILADTNSDRLFTVNDVTVGGSKYGIINLQSLKTPTLKVFMPRKPPILTNRKVNTSVCWASLNHLDSHILICLMGLAETPGCATLLPASLFVNSPHPGIDRPGMLCSFRIPGGAWSCAWSLNIQANNCFSTGLSRRVLLTNVVTGHRQSFGTNSDVLAQQFALMAPLLFNGCRSGEIFAIDLRCGNQGKGWKATRLFHDSAVTSVRILQDEQYLMASDMAGKIKLWDLRTTKCVRQYEGHVNEYAYLPLHVHEEEGILVAVGQDCYTRIWSLHDARLLRTIPSPYPASKADIPSVAFSSRLGGSRGRAGAAHGCRAGPLLLLLQLILQGTAQSHVDLTYGSKA


[0342] Further analysis of the NOV4a protein yielded the following properties shown in Table 4B.
19TABLE 4BProtein Sequence Properties NOV4aPsort0.9600 probability located in nucleus; 0.4776 probabilityanalysis:located in mitochondrial matrix space; 0.3000 probabilitylocated in microbody (peroxisome); 0.1837 probability locatedin mitochondrial inner membraneSignalPNo Known Signal Sequence Predictedanalysis:


[0343] A search of the NOV4a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 4C.
20TABLE 4CGeneseq Results for NOV4aNOV4aIdentities/Protein/Residues/SimilaritiesGeneseqOrganism/LengthMatchfor theExpectIdentifier[Patent #, Date]ResiduesMatched RegionValueABB11794Human secreted1 . . . 484470/484 (97%)0.0protein5 . . . 485471/484 (97%)homologue SEQID NO:2164—Homo sapiens,500 aa.[WO200157188-A2, Aug. 9,2001]AAM79804Human protein1 . . . 484470/484 (97%)0.0SEQ ID NO5 . . . 485471/484 (97%)3450—Homosapiens, 500 aa.[WO200157190-A2, Aug. 9,2001]AAM41122Human poly-1 . . . 484470/484 (97%)0.0peptide SEQ ID5 . . . 485471/484 (97%)NO 6053—Homosapiens, 500 aa.[WO200153312-A1, Jul. 26,2001]AAG67256Amino acid1 . . . 484459/484 (94%)0.0sequence of a1 . . . 474462/484 (94%)human liver-associated gene—Homo sapiens,489 aa.[WO200109318-A1, Feb. 8,2001]AAB94587Human protein1 . . . 484459/484 (94%)0.0sequence SEQ ID1 . . . 474462/484 (94%)NO:15389—Homo sapiens,489 aa.[EP1074617-A2,Feb. 7, 2001]


[0344] In a BLAST search of public sequence databases, the NOV4a protein was found to have homology to the proteins shown in the BLASTP data in Table 4D.
21TABLE 4DPublic BLASTP Results for NOV4aIdentities/NOV4aSimilaritiesProteinResidues/for theAccessionProtein/MatchMatchedExpectNumberOrganism/LengthResiduesPortionValueAAH18979HYPOTHETICAL 1 . . . 484470/4840.055.7 KDA(97%)PROTEIN— 1 . . . 480471/484Homo sapiens(97%)(Human), 495 aa.Q96K22CDNA FLJ14839 1 . . . 484459/4840.0FIS, CLONE(94%)OVARC1001791— 1 . . . 474462/484Homo sapiens(94%)(Human), 489 aa.Q9Y4P5HYPOTHETICAL 5 . . . 435420/4310.048.5 KDA(97%)PROTEIN— 2 . . . 428421/431Homo sapiens(97%)(Human), 430 aa(fragment).Q99LF7HYPOTHETICAL 1 . . . 484378/4850.058.1 KDA(77%)PROTEIN— 1 . . . 481423/485Mus musculus(86%)(Mouse), 519 aa.Q9UF10HYPOTHETICAL269 . . . 483175/2154e−9926.0 KDA(81%)PROTEIN— 4 . . . 217193/215Homo sapiens(89%)(Human), 234 aa(fragment).


[0345] PFam analysis predicts that the NOV4a protein contains the domains shown in the Table 4E.
22TABLE 4EDomain Analysis of NOV4aIdentities/NOV4aSimilarities forPfam DomainMatch Regionthe Matched RegionExpect ValueWD40: domain281 . . . 316 2/37 (5%) 5.8e+021 of 326/37 (70%)WD40: domain367 . . . 40210/37 (27%)6.12 of 327/37 (73%)WD40: domain408 . . . 44610/39 (26%)133 of 323/39 (59%)



Example 5

[0346] The NOV5 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 5A.
23TABLE 5ANOV5 Sequence AnalysisSEQ ID NO:131081 bpNOV5a,AGGATGGCCCAGAAGGAGAACAGTTATCCCTGGCCCTATGGCAAGCAGACGGCTCCAGCG58473-01 DNA SequenceCCGGCCTGAGTACCCTGCTCCCGCGAGTCCTCCCGAGGATCCCCACCGAAGCTGCGCGTGAGCTCCCGAGCTGCGCAGACCCACAGCCCGCAGCGGCCCCTGGCCATGAGGTGGTAGAGAACAGTTGTGGGAAGCGCAGCATCTTAACGCGGCCCTTCCTGGTCGACGACCTTGAGACTGGGCGTCCCCTGGGCAAAGACAAGTTTGTACATGTGTACTTGGCTCGAAAGAAGACAAGCCATTTCATCGTGGCCCTCAAGGCCTTCAAGTCTCAGATAGAGGAGGGCGTGGAGCACCAGATGCGCAGGCAGATGGAAATCCAGGCCCCCTTTCAGCATCCCAACATATTGAGTCTCTACAACTATTTTTATGACCTGAGAAAAATCTACTGGATTCTAGAGTACGCCCCCGCCACCCCTACCCCCGAGGAGCTGTACCAGGAGCTGCGAAAGAGCCGCACCTTTGACAAGAAGCCAACAGCCACCATCACGGGGGAGGTGGCAGATGCTCTGATGTACTGCCGAGCACCAGATGCGCAGGCAGATGGAAATCCAGGCCCCCTTTCAGCATCCCAACATATTGAGTCTCTACAACTATTTTTATGACCTGAGAAAAATCTACTGGATTCTAGAGTACGCCCCCGCCACCCCTACCCCCGAGGAGCTGTACCAGGAGCTGCGAAAGAGCCGCACCTTTGACAAGAAGCCAACAGCCACCATCACGGGGGAGGTGGCAGATGCTCTGATGTACTGCCACGGGAAGAAGGTGACTCCCAGAGACATGAAGCCAGATAATCTACTCTCAGGGCTTGAGGGCGAGCTGAAAGTTGCCGACTTCGGCTGCCCTGTGCACGCCCCCTCACTGAGGAGGAAGACAAGACAAATGTGTGGCACCCTGGACTACCTGTCCCCAGAGACAATTGAGGGGCGCGCGCACACCGAGAAGGTGGATTTGTGGTACATCGGAGCACTCGGCTATGAGCCGCTGGTGGGGAACCCCACACACAATGAGGCCTATGGGCGAATCGTCAAGGTGGCCCTAAAATTCCCCCTTCTGTGCCCAGGAGAGCCCCAGGACCTCATCTCCAAGCTGCTTAGGCATAACCCCTCAGAACGGCTGCCCCTGGCCCAGGTCTCAGCCCACCCTGGGATCCTGGCCCATTCTCGGAGGGTTTTGCCTCCCTCTGCCCATCAGTCTGTCCCCTGGTGGTCCCTGACATTCACTCGGGGGCGTCTGTGTTTGTAAGTCTGCATATORF Start: ATG at 4ORF Stop: TAA at 1069SEQ ID NO:14355 aaMW at 40012.7 kDNOV5a,MAQKENSYPWPYGKQTAPAGLSTLLPRVLPRIPTEAARELPSCADPQPAAAPGHEVVECG58473-01 Protein SequenceNSCGKRSILTRPFLVDDLETGRPLGKDKFVHVYLARKKTSHFIVALKAFKSQIEEGVEHQMRRQMEIQAPFQHPNILSLYNYFYDLRKIYWILEYAPATPTPEELYQELRKSRTFDKKPTATITGEVADALMYCHGKKVTPRDMKPDNTLLSGLEGELKVADFGCPVHAPSLRRKTRQMCGTLDYLSPETIEGRAHTEKVDLWYIGALGYEPLVGNPTHNEAYGRIVKVALKFPLLCPGEPQDLISKLLRHNPSERLPLAQVSAHPGILAHSRRVLPPSAHQSVPWWSLTFTRGRLCL


[0347] Further analysis of the NOV5a protein yielded the following properties shown in Table 5B1
24TABLE 5BProtein Sequence Properties NOV5aPsort0.4500 probability located in cytoplasm; 0.3000 probabilityanalysis:located in microbody (peroxisome); 0.1897 probability locatedin lysosome (lumen); 0.1000 probability located inmitochondrial matrix spaceSignalPNo Known Signal Sequence Predictedanalysis:


[0348] A search of the NOV5a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 5C.
25TABLE 5CGeneseq Results for NOV5aNOV5aIdentities/Protein/Residues/SimilaritiesGenseqOrganism/LengthMatchfor theExpectIdentifier[Patent #, Date]ResiduesMatched RegionValueAAG67615Amino acid1 . . . 341247/349 (70%)e−129sequence of1 . . . 343274/349 (77%)a human[WO200109316-A1, Feb. 8, 2001]AAG67436Amino acid1 . . . 341247/349 (70%)e−129sequence of a1 . . . 343274/349 (77%)human poly-peptide—Homosapiens, 344 aa.[WO200109345-A1, Feb. 8, 2001]AAY22475Human AUR11 . . . 341247/349 (70%)e−129protein1 . . . 343274/349 (77%)sequence—Homosapiens, 344 aa.[WO9937788-A2,Jul. 29, 1999]AAW18083Human Aurora-1 . . . 341247/349 (70%)e−1291—Homo1 . . . 343274/349 (77%)sapiens, 344 aa.[WO9722702-A1,Jun. 26, 1997]AAY27052Human protein1 . . . 341246/352 (69%)e−127kinase (HPKM)-11 . . . 346274/352 (76%)(clone ID2940)—Homosapiens, 347 aa.[WO9938981-A2,Aug. 5, 1999]


[0349] In a BLAST search of public sequence databases, the NOV5a protein was found to have homology to the proteins shown in the BLASTP data in Table 5D.
26TABLE 5DPublic BLASTP Results for NOV5aNOV5aIdentities/ProteinResidues/SimilaritiesAccessionProtein/Matchfor theExpectNumberOrganism/LengthResiduesMatched PortionValueO60446AURORA-1 . . . 341247/349 (70%)e−128RELATED1 . . . 343274/349 (77%)KINASE 2(SERINE/THREONINEKINASE 12)—Homo sapiens (Human), 344 aa.Q96GD4UNKNOWN1 . . . 341247/349 (70%)e−128(PROTEIN FOR1 . . . 343274/349 (77%)MGC:11031)—Homo sapiens(Human), 344 aa.Q96DV5UNKNOWN1 . . . 341247/350 (70%)e−126(PROTEIN FOR1 . . . 344274/350 (77%)MGC:4243)—Homo sapiens(Human), 345 aa.Q9UQ46AIK2—Homo1 . . . 341245/348 (70%)e−126sapiens (Human),1 . . . 342272/348 (77%)343 aa.O14630PROTEIN1 . . . 341245/352 (69%)e−125KINASE—Homo1 . . . 346272/352 (76%)sapiens (Human),347 aa.


[0350] PFam analysis predicts that the NOV5a protein contains the domains shown in the Table SE.
27TABLE 5EDomain Analysis of NOV5aIdentities/NOV5aSimilarities forExpectPfam DomainMatch Regionthe Matched RegionValuePkinase: domain76 . . . 325 81/293 (28%)6.5e−361 of 1184/293 (63%)



Example 6

[0351] The NOV6 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 6A.
28TABLE 6ANOV6 Sequence AnalysisSEQ ID NO:151524 bpNOV6a,AGCATTATGAACACTAATGACCTTAAACTCAGGTTGTCCAAAGCTGAGCAAGAACACCCG58470-01 DNA SequenceCACTACGTTTCTGGAATGAGCTTGAAGAAGCCCGACAGGTAGAACTTTATGCAGAGCTCCAGGCCATCGACTTTCAGGAACTGAACTTCTTTTTCCAAAAGGCCATTGAAGGATTTAACCAGTCCTCTCATCAAGAAAAGGTGGATGCGGGAATGGAACCTGTCCCTCGAGAAGTACTGGGCAGTGCTGCAGGGAAGCTAGATCAGCTCCAGGCCTGGGAAAGCAAAGTTTTCCAGATTTCTGAGAACAAAGTCACAGTTGTTCTAGCTGGTGGGCAGGGGACTAGACTCGTTGCATATCCAAAGGGGATGTATGATGTTGGTTTGCCATCCCATAAGACACTTTTTCAGATTCAAGCAGAGCATATCCTGAAGCTACAACAGTTAGCTGAAAAATATTATGGCAACAAATGCATTATTCCATATTACGTCATGACCAGCGAGTTCACTCTGGGGCCCACGGCCGAGTTCTTCAGGGAGCACAACTTCTTCCACCTGGACCCCGCCAACGTGGTCATGTTTGAGCAGCGCCTGCTGCCTGCTGTGACCTTTGATGGCAAGGTTATCCTGGAGCGGAAAGACAAAGTTGCCATGGCCCCAGACGGCAACGGGGGCCTCTACTGCGCGCTGGAGGACCACAAGATCCTGGAGGACATGGAGCGCCGGGGAGTGGAGTTTGTGCACGTGTACTGTGTGGACAACATCCTGGTGCGGCTGGCGGACCCTGTCTTCATCGGCTTCTGTGTGTTGCAGGGCGCAGACTGTGGCGCCAAGGTGGTGGAAAAGGCATACCCCGAGGAGCCCGTGGGCGTGGTGTGCCAGGTGGACGGTGTCCCCCAGGTGGTGGAGTACAGCGAGATCAGTCCTGAGACCGCACAGCTACGTGTCTCCGACGGGAGCCTGCTGTACAATGCAGGCAACATCTGCAACCACTTCTTCACCCGAGGCTTCCTTAAGGCGGTCACCAGGGAGTTTGAGCCTTTGCTGAAGCCACACGTGGCTGTGAAGAAGGTCCCGTATGTGGATGAGGAGGGGAATCTGGTAAAGCCGCTAAAACCGAACGGGATAAAGATGGAGAAGTTTGTGTTTGATGTGTTCCGGTTTGCTAAGAACTTTGCTGCCTTGGAAGTGCTGCGGGAGGAGGAATTTTCCCCACTGAAGAACGCAGAGCCAGCCGACAGGGACAGTCCCCGCACCGCTCGCCAGGCCCTGCTCACCCAGCACTACCGGTGGGCTCTGCGGGCCGGGGCCCGCTTCCTGGATGCCCATGGGGCCCGGCTCCCAGAGCTGCCCAGCTTGCCCCCAAATGGAGACCCTCCGGCCATCTGTGAGATATCGCCCTTGGTGTCTTACTCTGGAGAGGGTTTAGAAGTGTACCTGCAAGGCCGGGAGTTCCAGTCCCCGCTCATCCTGGATGAAGACCAGGCCAGGGAGCTGGTGAAAAATGGTATATGAACCTGATACCAAORF Start: ATG at 7ORF Stop: TGA at 1510SEQ ID NO:16501 aaMW at 56461.0 kDNOV6a,MNTNDLKLRLSKAEQEHPLRFWNELEEARQVELYAELQAIDFQELNFFFQKAIEGFNQCG58470-01 Protein SequenceSSHQEKVDAGMEPVPREVLGSAAGKLDQLQAWESKVFQISENKVTVVLAGGQGTRLVAYPKGMYDVGLPSHKTLFQIQAEHILKLQQLAEKYYGNKCIIPYYVMTSEFTLGPTAEFFREHNFFHLDPANVVMFEQRLLPAVTFDGKVILERKDKVAMAPDGNGGLYCALEDHKILEDMERRGVEFVHVYCVDNILVRLADPVFIGFCVLQGADCGAKVVEKAYPEEPVGVVCQVDGVPQVVEYSEISPETAQLRVSDGSLLYNAGNICNHFFTRGFLKAVTREFEPLLKPHVAVKKVPYVDEEGNLVKPLKPNGIKMEKFVFDVFRFAKNFAALEVLREEEFSPLKNAEPADRDSPRTARQALLTQHYRWALRAGARFLDAHGARLPELPSLPPNGDPPAICEISPLVSYSGEGLEVYLQGREFQSPLILDEDQARELVKNGI


[0352] Further analysis of the NOV6a protein yielded the following properties shown in Table 6B.
29TABLE 6BProtein Sequence Properties NOV6aPSort0.4500 probability located in cytoplasm; 0.3490 probabilityanalysis:located in microbody (peroxisome); 0.1000 probability locatedin mitochondrial matrix space; 0.1000 probability locatedin lysosome (lumen)SignalPNo Known Signal Sequence Predictedanalysis:


[0353] A search of the NOV6a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 6C.
30TABLE 6CGeneseq Results for NOV6aNOV6aIdentities/Protein/Residues/Similarities forGeneseqOrganism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAB56960Human prostate 1 . . . 501353/522 (67%)0.0cancer antigen 3 . . . 524413/522 (78%)protein sequenceSEQ ID NO:1538—Homosapiens, 524 aa.[WO200055174-A1, Sep. 21,2000]AAG32392Arabidopsis 9 . . . 485194/489 (39%)3e−84thaliana protein36 . . . 497275/489 (55%)fragment SEQ IDNO: 39067—Arabidopsisthaliana, 502 aa.[EP1033405-A2,Sep. 6, 2000]AAG40236Arabidopsis 9 . . . 485193/488 (39%)3e−82thaliana protein12 . . . 472272/488 (55%)fragment SEQ IDNO: 49896—Arabidopsisthaliana, 477 aa.[EP1033405-A2,Sep. 6, 2000]AAG40235Arabidopsis 9 . . . 485193/488 (39%)3e−82thaliana protein35 . . . 495272/488 (55%)fragment SEQ IDNO: 49895—Arabidopsisthaliana, 500 aa.[EP1033405-A2,Sep. 6, 2000]AAG40234Arabidopsis 9 . . . 485193/488 (39%)3e−82thaliana protein40 . . . 500272/488 (55%)fragment SEQ IDNO: 49894—Arabidopsisthaliana, 505 aa.[EP1033405-A2,Sep. 6, 2000]


[0354] In a BLAST search of public sequence databases, the NOV6a protein was found to have homology to the proteins shown in the BLASTP data in Table 6D.
31TABLE 6DPublic BLASTP Results for NOV6aNOV6aIdentities/ProteinResidues/Similarities forAccessionProtein/Matchedthe MatchedExpectNumberOrganism/LengthResiduesPortionValueQ96GM2UDP-N- 1 . . . 501351/505 (69%)0.0ACTEYL- 1 . . . 505412/505 (81%)GLUCOSAMINEPYROPHOS-PHORYLASE1—Homo sapiens(Human), 505 aa.Q16222UDP-N-acetyl- 1 . . . 501352/522 (67%)0.0hexosamine pyro- 1 . . . 522412/522 (78%)phosphorylase(Antigen X)(AGX) (Sperm-associatedantigen 2)[Includes: UDP-N-acetylgalactos-amine pyro-phosphorylase(EC 2.7.7.-)(AGX-1); UDP-N-acetylglucos-amine pyro-phosphorylase(EC 2.7.7.23)(AGX-2)]—Homo sapiens(Human), 522 aa.Q91YN5HYPO- 1 . . . 501342/522 (65%)0.0THETICAL 1 . . . 522407/522 (77%)58.6 KDAPROTEIN—Mus musculus(Mouse), 522 aa.AAH17547HYPO- 1 . . . 501341/521 (65%)0.0THETICAL 1 . . . 521407/521 (77%)58.5 KDAPROTEIN—Mus musculus(Mouse), 521 aa.Q9Y0Z0BCDNA: 6 . . . 492236/491 (48%)e−124LD2463944 . . . 513330/491 (67%)PROTEIN—Drosophilamelanogaster(Fruit fly),520 aa.


[0355] PFam analysis predicts that the NOV6a protein contains the domains shown in the Table 6E.
32TABLE 6EDomain Analysis of NOV6aIdentities/NOV6aSimilarities forExpectPfam DomainMatch Regionthe Matched RegionValueUDPGP: domain40 . . . 434108/428 (25%)8.4e−1111 of 1324/428 (76%)



Example 7

[0356] The NOV7 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 7A.
33TABLE 7ANOV7 Sequence AnalysisSEQ ID NO:17461 bpNOV7a,ACGCAGAGATGCAGATCTTTGTGAAGACCCTCACGGGCAAGACCATCACCCTTGAGGTCG58593-01 DNA SequenceCAAGCCCACCGACACCATTGAGAATGTCAAAACCAAAATTCAGGACAAGGAGGGTATCCCACCTGACCAGCAGCGTCTGATATTTGCTGGGAAACGGCTGGAGGATGGCCACACTCTCTCAGGCTACAACATCCAGAAAGAGTCCACCCTAAACCTGGTGCTGCGCCTGCGAGGTGGCATTACTGAGCCTTCCCTCCGCCAGCTCGTCCAGAAATACAACTGCGACGAGATGATCTGCTGCAAGTGCTATGCTTGCCTGCACCCCGGTGCTATCAACTGCCACAAGAAGAAATGCGGCCACACCAACAACCTGTACCCCAGGAAGAAGGTCAAATAAGGCTCTTCCTTCCTTGAAGGGCAGCAGCCTTCTGCCCAGGCCCCATGGCCCTGGGGCCTCAATAAAORF Start: ATG at 9ORF Stop: TAA at 393SEQ ID NO:18128 aaMW at 14540.9 kDNOV7a,MQIFVKTLTGKTITLEVKPTDTIENVKTKIQDKEGIPPDQQRLIFAGKRLEDGHTLSGCG58593-01 Protein SequenceYNIQKESTLNLVLRLRGGITEPSLRQLVQKYNCDEMICCKCYACLHPGAINCHKKKCGHTNNLYPRKKVK


[0357] Further analysis of the NOV7a protein yielded the following properties shown in Table 7B.
34TABLE 7BProtein Sequence Properties NOV7aPSort0.9800 probability located in nucleus; 0.1000 probabilityanalysis:located in mitochondrial matrix space; 0.1000 probabilitylocated in lysosome (lumen); 0.0000 probability located inendoplasmic reticulum (membrane)SignalPNo Known Signal Sequence Predictedanalysis:


[0358] A search of the NOV7a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 7C.
35TABLE 7CGeneseq Results for NOV7aIdentities/NOV7aSimilaritiesProtein/Residues/for theGeneseqOrganism/LengthMatchMatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAB52080Gene 16 human 1 . . . 128111/1287e−61secreted protein(86%)homologous amino 1 . . . 128118/128acid sequence(91%)#129—Sus scrofa,128 aa.[WO200061596-A1,Oct. 19, 2000]AAG43861Arabidopsis 1 . . . 128101/1289e−55thaliana protein(78%)fragment SEQ ID 1 . . . 128113/128NO: 54871—(87%)Arabidopsisthaliana, 128 aa.[EP1033405-A2,Sep. 6, 2000]AAG36188Arabidopsis 1 . . . 128101/1289e−55thaliana protein(78%)fragment SEQ ID122 . . . 249113/128NO: 44314—(87%)Arabidopsisthaliana, 249 aa.[EP1033405-A2,Sep. 6, 2000]AAG36187Arabidopsis 1 . . . 128101/1289e−55thaliana protein(78%)fragment SEQ ID137 . . . 264113/128NO: 44313—(87%)Arabidopsisthaliana, 264 aa.[EP1033405-A2,Sep. 6, 2000]AAG36186Arabidopsis 1 . . . 128101/1289e−55thaliana protein(78%)fragment SEQ ID195 . . . 322113/128NO: 44312—(87%)Arabidopsisthaliana, 322 aa.[EP1033405-A2,Sep. 6, 2000]


[0359] In a BLAST search of public sequence databases, the NOV7a protein was found to have homology to the proteins shown in the BLASTP data in Table 7D.
36TABLE 7DPublic BLASTP Results for NOV7aNOV7aIdentities/ProteinResidues/SimilaritiesAccessionProtein/Matchfor theExpectNumberOrganism/LengthResiduesMatched PortionValueQ9BX98UBIQUITIN 1 . . . 128111/128 (86%)3e−60A-52 RESIDUE14 . . . 141118/128 (91%)RIBOSOMALPROTEINFUSIONPRODUCT 1—Homo sapiens(Human), 141 aa(fragment).Q9UPK7UBIQUITIN-52 1 . . . 128111/128 (86%)3e−60AMINO ACID 1 . . . 128118/128 (91%)FUSIONPROTEIN—Homo sapiens(Human), 128 aa.Q9PT09UBIQUITIN— 1 . . . 128110/128 (85%)6e−60Oncorhynchus 1 . . . 128118/128 (91%)mykiss (Rainbowtrout) (Salmogairdneri),128 aa.O42388UBIQUITIN- 1 . . . 128110/128 (85%)7e−60RIBOSOMAL 1 . . . 128117/128 (90%)PROTEINFUSIONPROTEIN—Gallus gallus(Chicken),128 aa.Q9XSV1UBIQUITIN- 1 . . . 128110/128 (85%)1e−59RIBOSOMAL 1 . . . 128117/128 (90%)PROTEIN L40FUSIONPROTEIN—Canisfamiliaris(Dog), 128 aa.


[0360] PFam analysis predicts that the NOV7a protein contains the domains shown in the Table 7E.
37TABLE 7EDomain Analysis of NOV7aIdentities/NOV7aSimilarities forExpectPfam DomainMatch Regionthe Matched RegionValueubiquitin: domain1 . . . 7454/83 (65%)1.9e−381 of 172/83 (87%)Ribosomal_L40e:77 . . . 12830/52 (58%)7.3e−20domain 1 of 142/52 (81%)



Example 8

[0361] The NOV8 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 8A.
38TABLE 8ANOV8 Sequence AnalysisSEQ ID NO:192296 bpNOV8a,CGGCGGCGGCGGCAGTAGAAATGATGGAAGAATTGCATAGCCTGGACCCACGACGGCACG57871-01 DNA SequenceGAAATTATTGGAGGCCAGGTTTACTGGAGTAGGTGTTAGTAAGGGACCACTTAATAGTGAGTCTTCCAACCAGAGCTTGTGCAGCGTCGGATCCTTGAGTGATAAAGAAGTAGAGACTCCCAAGAAAAAGCAGAATGACCAGCGAAATCGGAAAAGAAAAGCTGAACCATATGAAAGTAGCCAAGGGAAAGGCACTCCTAGGGGACATAAAATTAGTGATTACTTTGAGTTTGCTGGGGGAAGCGGGCCGGGAACCAGCCCTGGCAGAAGTGTTCCACCAGTTGCACGATCCTCACTGCAACATTCTTTATCCAATCCCTTACCGCGACGAGTAGAACAGCCCCTCTATGGTTTAGATGGCAGTGCTGCAAAGGAGGCAACGGAGGAGCAGTCTGCTCTGCCAACCCTCATGTCAGTGATGCTAGCAAAACCTCGGCTTGACACAGAGCAGCTGGCGCAAAGGGGAGCTGGCCTCTGCTTCACTTTTGTTTCAGCTCAGCAAAACAGTCCCTCATCTACGGGATCTGGCAACACAGAGCATTCCTGCAGCTCCCAAAAACAGATCTCCATCCAGCACAGACAGACCCAGTCCGACCTCACAATAGAAAAAATATCTGCACTAGAAAACAGTAAGAATTCTGACTTAGAGAAGAAGGAGGGAAGAATAGATGATTTATTAAGAGCCATCTGTGATTTGAGACGGCAGATTGATGAACAGCAAAAGATGCTAGAGAAATACAAGGAACGATTAAATAGATGTGTGACAATGAGCAAGAAACTCCTTATAGAAAAGTCAAAACAAGAGAAGATGGCGTGTAGAGATAAGAGCATGCAAGACCGCTTGAGACTGGGCCACTTTACTACGTCTGACCACGGAGCCAAATTTACTGAGCAGTGGACAGATGGTTATGCTTTTCAGAATCTTATCAAGCAACAGGAAAGGATAAATTCACAGAGGGAAGAGATAGAAAGACAACGGAAAATGTTAGCAAAGCGGAAACCTCCTGCCATGGGTCAGGCCCCTCCTGCAACCAATGAGCAGAAACAGTGGAAAAGCAAGACCAATGGAGCTGAAAATGAAACGTTAACGTTAAAAGAATACCATGAACAAGAAGAAATCTTCAAACTCAGATTAGGTCATCTTAAAAAGGAGGAAGCAGAGATCCAGGCAGAGCTGGAGAGGCTAGAAAGGGTTAGAAAACTACATATCAGGGAAGTAAAAAGGATACATAATGAAGATAATTCACAATTTAAATATCATCCAACGCTAAATGACAGATATTTGTTGTTACATCTTTTGGGTAGAGGAGGTTTCAGTGAAGTTTACAAGGCATTTGATCTAACAGAGCAAAGATACGTAGCTGTGAAAATTCACCAGTTAAATAAAAACTGGAGAGATGAGAAAAAGGAGAATTACCACAAGCATGCATGTAGGGAATACCGGATTCATAAAGAGCTGGACCATCCCAGAATAGTTAAGCTGTATGATTACTTTTCACTGGATACTGACTCGTTTTGTACAGTATTAGAATACTGTGAGGGAAATGATCTGGACTTCTACCTGAAACAGCACAAATTAATGTCAGAGAAAGAGGCCCGGTCCATTATCATGCAGATTGTGAATGCTTTAAAGTACTTAAATGAAATAAAACCTCCCATCATACACTATGACCTCAAACCAGGTAATATTCTTTTAGAAAATGGTACAGCGTGTGGAGAGATAAAAATTACAGATTTTGGTCTTTCGAAGATCATGGATGATGATAGCTACAATTCAGTGGATGGCATGGAGCTAACATCACAAGGTGCTGGTACTTATTGGTATTTACCACCAGAGTGTTTTGTGGTTGGGAAAGAACCACCAAAGATCTCAAATAAAGTTGATGTGTGGTCGGTGGGTGTGATCTTCTATCAGTGTCTTTATGGAAGGAAGCCTTTTGGCCATAACCAGTCTCAGCAAGACATCCTACAAGAGAATACGATTCTTAAAGCTACTGAAGTGCAGTTCCCGCCAAAGCCGGTAGTAACACCTGAAGCAAAGGCGTTGATTCGACGATGCTTGGCCTACCGAAAGGAGGACCGCATTGATGTCCAGCAGCTGGCCTGTGATCCCTACTTGTTGCCTCACATCCGAAAGTCAGTCTCTACGAGTAGCCCTGCTGGAGCTGCTATTGCATCAACCTCTGGGGCGTCCAATAACAGTTCTTCTAATTGAGACTGACTCCAAGGCCACAAACTORF Start: ATG at 24ORF Stop: TGA at 2271SEQ ID NO:20749 aaMW at 8545.8 kDNOV8a,MEELHSLDPRRQKLLEARFTGVGVSKGPLNSESSNQSLCSVGSLSDKEVETPKKKQNDCG57871-01 Protein SequenceQRNRKRKAEPYESSQGKGTPRGHKISDYFEFAGGSGPGTSPGRSVPPVARSSLQHSLSNPLPRRVEQPLYGLDGSAAKEATEEQSALPTLMSVMLAKPRLDTEQLAQRGAGLCFTFVSAQQNSPSSTGSGNTEHSCSSQKQISIQHRQTQSDLTIEKISALENSKNSDLEKKEGRIDDLLRAICDLRRQIDEQQKMLEKYKERLNRCVTMSKKLLIEKSKQEKMACRDKSMQDRLRLGHFTTSDHGAKFTEQWTDGYAFQNLIKQQERINSQREEIERQRKMLAKRKPPAMGQAPPATNEQKQWKSKTNGAENETLTLKEYHEQEEIFKLRLGHLKKEEAEIQAELERLERVRKLHIREVKRIHNEDNSQFKYHPTLNDRYLLLHLLGRGGFSEVYKAFDLTEQRYVAVKIHQLNKNWRDEKKENYHKHACREYRIHKELDHPRIVKLYDYFSLDTDSFCTVLEYCEGNDLDFYLKQHKLMSEKEARSIIMQIVNALKYLNEIKPPIIHYDLKPGNILLENGTACGEIKITDFGLSKIMDDDSYNSVDGMELTSQGAGTYWYLPPECFVVGKEPPKISNKVDVWSVGVIFYQCLYGRKPFGHNQSQQDILQENTILKATEVQFPPKPVVTPEAKALIRRCLAYRKEDRIDVQQLACDPYLLPHIRKSVSTSSPAGAAIASTSGASNNSSSN


[0362] Further analysis of the NOV8a protein yielded the following properties shown in Table 8B.
39TABLE 8BProtein Sequence Properties NOV8aPSort0.9600 probability located in nucleus; 0.1000 probabilityanalysis:located in mitochondrial matrix space; 0.1000 probabilitylocated in lysosome (lumen); 0.0000 probability locatedin endoplasmic reticulum (membrane)SignalPNo Known Signal Sequence Predictedanalysis:


[0363] A search of the NOV8a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 8C.
40TABLE 8CGeneseq Results for NOV8aNOV8aIdentities/Protein/Residues/Similarities forGeneseqOrganism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAM39278Human polypeptide SEQ ID NO1 . . . 749703/749(93%)0.02423 - Homo sapiens, 718 aa.2 . . . 718707/749(93%)[WO200153312-A1, 26 JUL2001]AAM41064Human polypeptide SEQ ID NO1 . . . 749695/750(92%)0.05995 - Homo sapiens, 809 aa.92 . . . 809 701/750(92%)[WO200153312-A1, 26 JUL2001]AAR76062Protein kinase PKU beta - Homo210 . . . 749 525/540(97%)0.0sapiens, 540 aa. [JP07132093-A,1 . . . 540527/540(97%)23 MAY 1995]AAR76061Protein kinase PKU alpha - Homo1 . . . 744537/794(67%)0.0sapiens, 787 aa. [JP07132093-A,49 . . . 783 592/794(73%)23 MAY 1995]ABB20910Protein #2909 encoded by probe346 . . . 749 404/404(100%)0.0expression - Homo sapiens, 4041 . . . 404404/404(100%)aa. [WO200157274-A2, 09 AUG2001]


[0364] In a BLAST search of public sequence databases, the NOV8a protein was found to have homology to the proteins shown in the BLASTP data in Table 8D.
41TABLE 8DPublic BLASTP Results for NOV8aNOV8aIdentities/ProteinResidues/Similarities forAccessionMatchthe MatchedExpectNumberProtein/Organism/LengthResiduesPortionValueQ9UK17TOUSLED-LIKE KINASE 2 -1 . . . 749731/749 (97%)0.0Homo sapiens (Human), 749 aa.1 . . . 749736/749 (97%)O55047TOUSLED-LIKE KINASE - Mus1 . . . 749699/749 (93%)0.0musculus (Mouse), 717 aa.1 . . . 717705/749 (93%)Q9Y4F7PKU-ALPHA - Homo sapiens1 . . . 749700/749 (93%)0.0(Human), 719 aa (fragment).3 . . . 719705/749 (93%)Q9D5Y5TOUSLED-LIKE KINASE 21 . . . 656629/656 (95%)0.0(ARABIDOPSIS) - Mus musculus1 . . . 656640/656 (96%)(Mouse), 696 aa.Q90ZY7PKU-ALPHA PROTEIN KINASE -1 . . . 749580/753 (77%)0.0Brachydanio rerio (Zebrafish)2 . . . 697626/753 (83%)(Zebra danio), 697 aa.


[0365] PFam analysis predicts that the NOV8a protein contains the domains shown in the Table 8E.
42TABLE 8EDomain Analysis of NOV8aIdentities/SimilaritiesPfam DomainNOV8a Match Regionfor the Matched RegionExpect ValueA2M: domain 1 of 1501 . . . 52310/23(43%)4.620/23(87%)Pkinase: domain 1 of439 . . . 71896/316(30%)5.4e−701213/316(67%)



Example 9

[0366] The NOV9 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 9A.
43TABLE 9ANOV9 Sequence AnalysisSEQ ID NO:212060 bpNOV9a,GTTTTCATAGATAACCATGCAACATCCCATATGAATGGGCATGTTACAGAGGAATCACG58590-01 DNA SequenceGACAGCGAAGTAAAAAATGTTGATCTTGCATCACCAGAGGAACATCAGAAGCACCGAGAGATGGCTGTTGACTGCCCTGGAGATTTGGGCACCAGGATGATGCCAATACGTCGAAGTGCACAGTTGGAGCGTATTCGGCAACAACAGGAGGACATGAGGCGTAGGAGAGAGGAAGAAGGGAAAAAGCAAGAACTTGACCTTAATTCTTCCATGAGACTTAAGAAACTAGCCCAAATTCCTCCAAAGACCGGAATAGATAACCCTATGTTTGATACAGAGGAAGGAATTGTCTTAGAAAGTCCTCATTATGCTGTGAAAATATTAGAAATAGAAGACTTGTTTTCTTCACTTAAACATATCCAACATACTTTGGTAGATTCTCAGAGCCAGGAGGATATTTCACTGCTTTTACAACTTGTTCAAAATAAGGATTTCCAGAATGCATTTAAGATACACAATGCCATCACAGTACACATGAACAAGGCCAGTCCTCCATTTCCTCTTATCTCCAACGCACAAGATCTTGCTCAAGAGGTACAAACTGTTTTGAAGCCAGTTCATCATAAGGAAGGACAAGAACTAACTGCTTTGCTGAATACTCCACATATTCAGGCACTTTTACTGGCCCACGATAAGGTTGCTGAGCAGGAAATGCAGCTAGAGCCCATTACAGATGAGAGAGTTTATGAAAGTATTGGCCAGTATGGAGGAGAAACTGTAAAAATAGTTCGTATAGAAAAGGCTCGTGATATTCCGTTGGGTGCTACAGTTCGTAATGAAATGGACTCTGTCATCATTAGCCGGATAGTAAAAGGGGGTGCTGCAGAGAAAAGTGGTCTGTTGCATGAAGGAGATGAAGTTCTAGAGATTAATGGCATTGAAATTCGGGGGAAAGATGTCAATGAGGTTTTTGACTTGTTGTCTGATATGCATGGTACTTTGACTTTTGTCCTGATTCCCAGTCAACAGATCAAGCCGCCTCCTGCCAAGGAAACAGTAATCCATGTAAAAGCTCATTTTGACTATGACCCCTCAGATGACCCTTATGTTCCATGTCGAGAGTTAGGTCTGTCTTTTCAAAAAGGTGATATACTTCATGTGATCAGTCAAGAAGATCCAAACTGGTGGCAGGCCTACAGGGAAGGGGACGAAGATAATCAACCTCTAGCCGGGCTTGTTCCAGGGAAAAGCTTTCAGCAGCAAAGGGAAGCCATGAAACAAACCATAGAAGAAGATAAGGAGCCAGAAAAATCAGGTAAACTGTGGTGTGCAAAGAAGAATAAAAAGAAGAGGAAAAAGGTTTTATATAATGCCAATAAAAATGATGATTATGACAACGAGGAGATCTTAACCTATGAGGAAATGTCACTTTATCATCAGCCAGCAAATAGGAAGAGACCTATCATCTTGATTGGTCCACAGAACTGTGGCCAGAATGAATTGCGTCAGAGGCTCATGAACAAAGAAAAGGACCGCTTTGCATCTGCAGTTCCTCGTACAACCCGGAGTAGGCGAGACCAAGAAGTAGCCGGTAGAGATTACCACTTTGTTTCGCGGCAAGCATTCGAGGCAGACATAGCAGCTGGAAAGTTCATTGAGCATGGTGAATTTGAGAAGAATTTGTATGGAACTAGCATAGATTCTGTACGGCAAGTGATCAACTCTGGCAAAATATGTCTTTTAAGTCTTCGTACACAGTCATTGAAGACTCTCCGGAATTCAGATTTGAAACCATATATTATCTTCATTGCACCCCCTTCACAAGAAAGACTTCGGGCATTATTGGCCAAAGAAGGCAAGAATCCAAAGCCTGAAGAGTTGAGAGAAATCATTGAGAAGACAAGAGAGATGGAGCAGAACAATGGCCACTACTTTGATACGGCAATTGTGAATTCCGATCTTGATAAAGCCTATCAGGAATTGCTTAGGTTAATTAACAAACTTGATACTGAACCTCAGTGGGTACCATCCACTTGGCTGAGGTGAAAGAAACATCCATTCTORF Start: ATG at 17ORF Stop: TGA at 2042SEQ ID NO:22675 aaMW at 77311.8 kDNOV9a,MTTSHMNGHVTEESDSEVKNVDLASPEEHQKHREMAVDCPGDLGTRMMPIRRSAQLERCG58590-01 Protein SequenceIRQQQEDMRRRREEEGKKQELDLNSSMRLKKLAQIPPKTGIDNPMFDTEEGIVLESPHYAVKILEIEDLFSSLKHIQHTLVDSQSDEDISLLLQLVQNKDFQNAFKIHNAITVHMNKASPPFPLISNAQDLAQEVQTVLKPVHHKEGQELTALLNTPHIQALLLAHDKVAEQEMQLEPITDERVYESIGQYGGETVKIVRIEKARDIPLGATVRNEMDSVIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLLSDMHGTLTFVLIPSQQIKPPPAKETVIHVKAHFDYDPSDDPYVPCRELGLSFQKGDILHVISQEDPNWWQAYREGDEDNQPLAGLVPGKSFQQQREAMKQTIEEDKEPEKSGKLWCAKKNKKKRKKVLYNANKNDDYDNEEILTYEEMSLYHQPANRKRPIILIGPQNCGQNELRQRLMNKEKDRFASAVPRTTRSRRDQEVAGRDYHFVSRQAFEADIAAGKFIEHGEFEKNLYGTSIDSVRQVINSGKICLLSLRTQSLKTLRNSDLKPYIIFIAPPSQERLRALLAKEGKNPKPEELREIIEKTREMEQNNGHYFDTAIVNSDLDKAYQELLRLINKLDTEPQWVPSTWLRSEQ ID NO:232030 bpNOV9b,CCATGACAACATCCCATATGAATGGGCATGTTACAGAGGAATCAGACAGCGAAGTAAACG58590-02 DNA SequenceAAATGTTGATCTTGCATCACCAGAGGAACATCAGAAGCACCGAGAGATGGCTGTTGACTGCCCTGGAGATTTGGGCACCAGGATGATGCCAATACGTCGAAGTGCACAGTTGGAGCGTATTCGGCAACAACAGGAGGACATGAGGCGTAGGAGAGAGGAAGAAGGGAAAAAGCAAGAACTTGACCTTAATTCTTCCATGAGACTTAAGAAACTAGCCCAAATTCCTCCAAAGACCGGAATAGATAACCCTATGTTTGATACAGAGGAAGGAATTGTCTTAGAAAGTCCTCATTATGCTGTGAAAATATTAGAAATAGAAGACTTGTTTTCTTCACTTAAACATATCCAACATACTTTGGTAGATTCTCAGAGCCAGGAGGATATTTCACTGCTTTTACAACTTGTTCAAAATAAGGATTTCCAGAATGCATTTAAGATACACAATGCCATCACAGTACATATGAACAAGGCCAGTCCTCCATTTCCTCTTATCTCCAACGCACAAGATCTTGCTCAAGAGGTACAAACTGTTTTGAAGCCAGTTCATCATAAGGAAGGACAAGAACTAACTGCTTTGCTGAATACTCCACATATTCAGGCACTTTTACTGGCCCACGATAAGGTTGCTGAGCAGGAAATGCAGCTAGAGCCCATTACAGATGAGAGAGTTTATGAAAGTATTGGCCAGTATGGAGGAGAAACTGTAAAAATAGTTCGTATAGAAAAGGCTCGTGATATTCCGTTGGGTGCTACAGTTCGTAATGAAATGGACTCTGTCATCATTAGCCGGATAGTAAAAGGGGGTGCTGCAGAGAAAAGTGGTCTGTTGCATGAAGGAGATGAAGTTCTAGAGATTAATGGCATTGAAATTCGGGGGAAAGATGTCAATGAGGTTTTTGACCTGTTGTCTGATATGCATGGTACTTTGACTTTTGTCCTGATTCCCAGTCAACAGATCAAGCCGCCTCCTGCCAAGGAAACAGTAATCCATGTAAAAGCTCATTTTGACTATGACCCCTCAGATGACCCTTATGTTCCATGTCGAGAGTTAGGTCTGTCTTTTCAAAAAGGTGATATACTTCATGTGATCAGTCAAGAAGATCCAAACTGGTGGCAGGCCTACAGGGAAGGGGACGAAGATAATCAACCTCTAGCCGGGCTTGTTCCAGGGAAAAGCTTTCAGCAGCAAAGGGAAGCCATGAAACAAACCATAGAAGAAGATAAGGAGCCAGAAAAATCAGGAAAACTGTGGTGTGCAAAGAAGAATAAAAAGAAGAGGAAAAAGGTTTTATATAATGCCAATAAAAATGATGATTATGACAACGAGGAGATCTTAACCTATGAGGAAATGTCACTTTATCATCAGCCAGCAAATAGGAAGAGACCTATCATCTTGATTGGTCCACAGAACTGTGGCCAGAATGAATTGCGTCAGAGGCTCATGAACAAAGAAAAGGACCGCTTTGCATCTGCAGTTCCTCATACAACCCGGAGTAGGCGAGACCAAGAAGTAGCCGGTAGAGATTACCACTTTGTTTCGCGGCAAGCATTCGAGGCAGACATAGCAGCTGGAAAGTTCATTGAGCATGGTGAATTTGAGAAGAATTTGTATGGAACTAGCATAGATTCTGTACGGCAAGTGATCAACTCTGGCAAAATATGTCTTTTAAGTCTTCGTACACAGTCATTGAAGACTCTCCGGAATTCAGATTTGAAACCATATATTATCTTCATTGCACCCCCTTCACAAGAAAGACTTCGGGCATTATTGGCCAAAGAAGGCAAGAATCCAAAGCCTGAAGAGTTGAGAGAAATCATTGAGAAGACAAGAGAGATGGAGCAGAACAATGGCCACTACTTTGATACGGCAATTGTGAATTCCGATCTTGATAAAGCCTATCAGGAATTGCTTAGGTTAATTAACAAACTTGATACTGAACCTCAGTGGGTACCATCCACTTGGCTGAGGTGAORF Start: ATG at 3ORF Stop: TGA at 2028SEQ ID NO:24675 aaMW at 77292.8 kDNOV9b,MTTSEMNGEVTEESDSEVKNVDLASPEEHQKHREMAVDCPGDLGTRMMPIRRSAQLERCG58590-02 Protein SequenceIRQQQEDMRRRREEEGKKQELDLNSSMRLKKLAQIPPKTGIDNPMFDTEEGIVLESPHYAVKILEIEDLFSSLKHIQHTLVDSQSDEDISLLLQLVQNKDFQNAFKIHNAITVHMNKASPPFPLISNAQDLAQEVQTVLKPVHHKEGQELTALLNTPHIQALLLAHDKVAEQEMQLEPITDERVYESIGQYGGETVKIVRIEKARDIPLGATVRNEMDSVIISRIVKGGAAEKSGLLHEGDEVLEINGIEIRGKDVNEVFDLLSDMHGTLTFVLIPSQQIKPPPAKETVIHVKAHFDYDPSDDPYVPCRELGLSFQKGDILHVISQEDPNWWQAYREGDEDNQPLAGLVPGKSFQQQREAMKQTIEEDKEPEKSGKLWCAKKNKKKRKKVLYNANKNDDYDNEEILTYEEMSLYHQPANRKRPIILIGPQNCGQNELRQRLMNKEKDRFASAVPHTTRSRRDQEVAGRDYHFVSRQAFEADIAAGKFIEHGEFEKNLYGTSIDSVRQVINSGKICLLSLRTQSLKTLRNSDLKPYIIFIAPPSQERLRALLAKEGKNPKPEELREIIEKTREMEQNNGHYFDTAIVNSDLDKAYQELLRLINKLDTEPQWVPSTWLR


[0367] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 9B.
44TABLE 9BComparison of NOV9a against NOV9b.Identities/ProteinNOV9a Residues/Similarities forSequenceMatch Residuesthe Matched RegionNOV9b1 . . . 675636/675 (94%)1 . . . 675636/675 (94%)


[0368] Further analysis of the NOV9a protein yielded the following properties shown in Table 9C.
45TABLE 9CProtein Sequence Properties NOV9aPSort0.7000 probability located in nucleus; 0.1000 probabilityanalysis:located in mitochondrial matrix space; 0.1000 probabilitylocated in lysosome (lumen); 0.0000 probability locatedin endoplasmic reticulum (membrane)SignalPNo Known Signal Sequence Predictedanalysis:


[0369] A search of the NOV9a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 9D.
46TABLE 9DGeneseq Results for NOV9aNOV9aIdentities/Residues/Similarities forGeneseqProtein/Organism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAB94180Human protein sequence SEQ ID173 . . . 675501/503 (99%)0.0NO:14494 - Homo sapiens, 503 aa. 1 . . . 503501/503 (99%)[EP1074617-A2, 7 FEB 2001]AAB41921Human ORFX ORF1685406 . . . 675261/270 (96%)e−147polypeptide sequence SEQ ID 1 . . . 269264/270 (97%)NO:3370 - Homo sapiens, 269 aa.[WO200058473-A2, 5 OCT 2000]AAU07123Human novel human protein, NHP143 . . . 674224/564 (39%)e−109#23 - Homo sapiens, 576 aa. 31 . . . 574339/564 (59%)[WO200161016-A2, 23 AUG 2001]AAU07119Human novel human protein, NHP143 . . . 654213/544 (39%)e−102#19 - Homo sapiens, 560 aa. 31 . . . 554327/544 (59%)[WO200161016-A2, 23 AUG 2001]AAU07115Human novel human protein, NHP143 . . . 606196/481 (40%)5e−97 #15 - Homo sapiens, 520 aa. 31 . . . 495300/481 (61%)[WO200161016-A2, 23 AUG 2001]


[0370] In a BLAST search of public sequence databases, the NOV9a protein was found to have homology to the proteins shown in the BLASTP data in Table 9E.
47TABLE 9EPublic BLASTP Results for NOV9aIdentities/NOV9aSimilaritiesProteinResidues/for theAccessionMatchMatchedExpectNumberProtein/Organism/LengthResiduesPortionValueQ9JLB2PALS1 - Mus musculus (Mouse), 1 . . . 675652/675 (96%)0.0675 aa. 1 . . . 675665/675 (97%)Q9H9Q0CDNA FLJ12615 FIS, CLONE173 . . . 675501/503 (99%)0.0NT2RM4001629, WEAKLY 1 . . . 503501/503 (99%)SIMILAR TO MAGUK P55SUBFAMILY MEMBER 3 - Homosapiens (Human), 503 aa.AAL40935STARDUST PROTEIN MAGUK1252 . . . 674252/460 (54%)e−140ISOFORM - Drosophila 829 . . . 1282327/460 (70%)melanogaster (Fruit fly), 1289 aa.Q9W3H6CG1617 PROTEIN - Drosophila252 . . . 674252/500 (50%)e−132melanogaster (Fruit fly), 794 aa.294 . . . 787327/500 (65%)Q9W7F1P55-RELATED MAGUK142 . . . 673209/556 (37%)e−105PROTEIN DLG3 - Brachydanio 30 . . . 573335/556 (59%)rerio (Zebrafish) (Zebra danio), 576 aa.


[0371] PFam analysis predicts that the NOV9a protein contains the domains shown in the Table 9F.
48TABLE 9FDomain Analysis of NOV9aIdentities/SimilaritiesPfam DomainNOV9a Match Regionfor the Matched RegionExpect ValueL27: domain 1 of 1186 . . . 23819/56(34%)0.04939/56(70%)PDZ: domain 1 of 1256 . . . 33521/83(25%)9.7e−1258/83(70%)SH3: domain 1 of 1348 . . . 41519/68(28%)0.02646/68(68%)Guanylate_kin: domain 1515 . . . 62454/113(48%)6.2e−38of 187/113(77%)Peptidase_S15: domain 1642 . . . 6586/17(35%)8.2of 113/17(76%)Caulimo_mov: domain 1420 . . . 67359/335(18%)6.1of 1156/335(47%)



Example 10

[0372] The NOV10 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 10A.
49TABLE 10ANOV10 Sequence AnalysisSEQ ID NO:25576 bpNOV10a,ACCTTACTAGAAAAATGAAACCTGATGAAACTCCTATGTTTGACCCAAGTCTACTCAACG58572-01 DNA SequenceAGAAGTGGACTGGAGTCAGAATACAGCTACATTTTCTCCAGCCATTTCCCCAACACATCCTGGAGAAGGCTTGGTTTTGAGGCCTCTTTGTACTGCTGACTTAAATAGAGGTTTTTTTAAGGTATTGGGTCAGCTAACAGAGACTGGAGTTGTCAGCCCTGAACAATTTATGGAATCTTTTGAGCATATGAAGAAATCTGGGGATTATTATGTTACAGTTGTAGAAGATGTGACTCTAGGACAGATTGTTGCTACGGCAACTCTGATTATAGAACATAAATTCATCCATTCCTGTGCTAAGAGAGGAAGAGTAGAAGATGTTGTTGTTAGTGATGAATGCAGAGGAAAGCAGCTTGGCAAATTGTTATTATCAACCCTTACTTTGCTAAGCAAGAAACTGAACTGTTACAAGATTACCCTTGAATGTCTACCACAAAATGTTGGTTTCTATAAAAAGTTTGGATATACTGTATCTGAAGAAAACTACATGTGTCGGAGGTTTCTAAAGTAAAAATCTTORF Start: ATG at 15ORF Stop: TAA at 567SEQ ID NO:26184 aaMW at 2079.9 kDNOV10a,MKPDETPMFDPSLLKEVDWSQNTATFSPAISPTHPGEGLVLRPLCTADLNRGFFKVLGCG58572-01 Protein SequenceQLTETGVVSPEQFMESFEHMKKSGDYYVTVVEDVTLGQIVATATLIEHKFIHSCAKRGRVEDVVVSDECRGKQLGKLLLSTLTLLSKKLNCYKITLECLPQNVGFYKKFGYTVSEENYMCRRFLKSEQ ID NO:27560 bpNOV10b,ATGAAACCTGATGAAACTCCTATGTTTGACCCAAGTCTACTCAAAGAAGTGGACTGGACG58572-02 DNA SequenceGTCAGAATACAGCTACATTTTCTCCAGCCATTTCCCCAACACATCCTGGAGAAGGCTTGGTTTTGGGGCCTCTTTGTACTGCTGACTTAAATAGAGGTTTTTTTAAGGTATTGGGTCAGCTAACAGAGACTGGAGTTGTCAGCCCTGAACAATTTATGAAATCTTTTGAGCATATGAAGAAATCTGGGGATTATTATGTTACAGTTGTAGAAGATGTGACTCTAGGACAGATTGTTGCTACGGCAACTCTGATTATAGAACATAAATTCATCCATTCCTGTGCTAAGAGAGGAAGAGTAGAAGATGTTGTTGTTAGTGATGAATGCAGAGGAAAGCAGCTTGGCAAATTGTTATTATCAACCCTTACTTTGCTAAGCAAGAAACTGAACTGTTACAAGATTACCCTTGAATGTCTACCACAAAATGTTGGTTTCTATAAAAAGTTTGGATATACTGTATCTGAAGAAAACTACATGTGTCGGAGGTTTCTAAAGTAAAAATCORF Start: ATG at 1ORF Stop: TAA at 553SEQ ID NO:28184 aaMW at 20649.8 kDNOV10b,MKPDETPMFDPSLLKEVDWSQNTATFSPAISPTHPGEGLVLGPLCTADLNRGFFKVLGCG5872-02 Protein SequenceQLTETGVVSPEQFMKSFEHMKKSGDYYVTVVEDVTLGQIVATATLIIEHKFIHSCAKRGRVEDVVVSDECRGKQLGKLLLSTLTLLSKKLNCYKITLECLPQNVGFYKKFGYTVSEENYMCRRFLK


[0373] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 10B.
50TABLE 10BComparison of NOV10a against NOV10b.Identities/ProteinNOV10a Residues/Similarities forSequenceMatch Residuesthe Matched RegionNOV10b1 . . . 184163/184 (88%)1 . . . 184164/184 (88%)


[0374] Further analysis of the NOV10a protein yielded the following properties shown in Table 10C.
51TABLE 10CProtein Sequence Properties NOV10aPSort0.4500 probability located in cytoplasm; 0.1206 probabilityanalysis:located in microbody (peroxisome); 0.1000 probability locatedin mitochondrial matrix space; 0.1000 probability located inlysosome (lumen)SignalPNo Known Signal Sequence Predictedanalysis:


[0375] A search of the NOV10a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 10D.
52TABLE 10DGeneseq Results for NOV10aNOV10aIdentities/Protein/Residues/Similarities forGeneseqOrganism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAG67123Amino acid sequence of human1 . . . 184183/184 (99%)e−10550287 transferase - Homo sapiens,1 . . . 184184/184 (99%)184 aa. [WO200164904-A2,7 SEP 2001]AAB73505Human transferase HTFS-12, SEQ1 . . . 184183/184 (99%)e−105ID NO: 12 - Homo sapiens, 184 aa.1 . . . 184184/184 (99%)[WO200132888-A2, 10 MAY2001]AAB63700Human gastric cancer associated1 . . . 184183/184 (99%)e−105antigen protein sequence SEQ ID17 . . . 200 184/184 (99%)NO:1062 - Homo sapiens, 200 aa.[WO200073801-A2, 7 DEC2000]AAU07779Human novel transferase protein,1 . . . 184182/184 (98%)e−104NHP #22 - Homo sapiens, 184 aa.1 . . . 184183/184 (98%)[WO200164903-A2, 7 SEP 2001]AAM79992Human protein SEQ ID NO 3638 -1 . . . 184181/184 (98%)e−104Homo sapiens, 206 aa.23 . . . 206 183/184 (99%)[WO200157190-A2, 9 AUG2001]


[0376] In a BLAST search of public sequence databases, the NOV10a protein was found to have homology to the proteins shown in the BLASTP data in Table 10E.
53TABLE 10EPublic BLASTP Results for NOV10aIdentities/NOV10aSimilaritiesProteinResidues/for theAccessionMatchMatchedExpectNumberProtein/Organism/LengthResiduesPortionValueQ96EK6SIMILAR TO GLUCOSAMINE-1 . . . 184183/184(99%) e−104PHOSPHATE N-1 . . . 184184/184(99%)ACETYLTRANSFERASE - Homosapiens (Human), 184 aa.Q9JK38EMEG32 PROTEIN1 . . . 184180/184(97%) e−102(GLUCOSAMINE-PHOSPHATE N-1 . . . 184182/184(98%)ACETYLTRANSFERASE) - Musmusculus (Mouse), 184 aa.Q9VAI0Probable glucosamine-phosphate N-4 . . . 17684/174(48%)2e−43acetyltransferase (EC 2.3.1.4)6 . . . 179123/174(70%)(Phosphoglucosamine transacetylase)(Phosphoglucosamine acetylase) -Drosophila melanogaster (Fruit fly),219 aa.Q17427Probable glucosamine-phosphate N-32 . . . 182 65/152(42%)1e−28acetyltransferase (EC 2.3.1.4)15 . . . 165 98/152(63%)(Phosphoglucosamine transacetylase)(Phosphoglucosamine acetylase) -Caenorhabditis elegans, 165 aa.O45811T23G11.2PROTEIN -42 . . . 184 63/143(44%)3e−26Caenorhabditis elegans, 347 aa.201 . . . 340 88/143(61%)


[0377] PFam analysis predicts that the NOV10a protein contains the domains shown in the Table 10F.
54TABLE 10FDomain Analysis of NOV10aIdentities/SimilaritiesPfam DomainNOV10a Match Regionfor the Matched RegionExpect ValueAcetyltransf: domain 189 . . . 17122/87 (25%)6.5e−13of 162/87 (71%)



Example 11

[0378] The NOV11 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 11A.
55TABLE 11ANOV11 Sequence AnalysisSEQ ID NO:297098 bpNOV11a,CCCGCGGGCCAGCACCATGGAGGACGTGAAGCTGGAGTTCCCTTCCCTTCCACAGTGCCG58564-01 DNA SequenceAAGGAAGACGCCGAGGAGTGGACCTACCCTATGAGACGAGAGATGCAGGAAATTTTACCTGGATTGTTCTTAGGCCCATATTCATCTGCTATGAAAAGCAAGCTACCTGTACTACAGAAACATGGAATAACCCATATAATATGCATACGACAAAATATTGAAGCAAACTTTATTAAACCAAACTTTCAGCAGTTATTTAGGTATTTAGTCCTGGATATTGCAGATAATCCAGTTGAAAATATAATACGTTTTTTCCCTATGACTAAGGAATTTATTGATGGGAGCTTACAAATGGGAGGTAAAGTTCTTGTGCATGGAAATGCAGGGATCTCCAGAAGTGCAGCCTTTGTTATTGCATACATTATGGAAACATTTGGAATGAAGTACAGGGATGCTTTTGCTTATGTTCAAGAAAGAAGATTTTGTATTAATCCTAATGCTGGATTTGTCCATCAACTTCAGGAATATGAAGCCATCTACCTAGCAAAATTAACAATACAGATGATGTCACCACTCCAGATAGAAAGGTCATTATCTGTTCATTCTGGTACCACAGGTAGTTTGAAGAGAACACATGAAGAAGAGGATGATTTTGGAACCATGCAAGTGGCGACTGCACAGAATGGCTGACTTGAAGAGCAACATCATAGAORF Start: ATG at 17ORF Stop: TGA at 686SEQ ID NO:30223 aaMW at 25492.2 kDNOV11a,MEDVKLEFPSLPQCKEDAEEWTYPMRREMQEILPGLEFLGPYSSAMKSKLPVLQKHGITCG58564-01 Protein SequenceHIICIRQNIEANFIKPNFQQLFRYLVLDIADNPVENIIRFFPMTKEFIDGSLQMGGKVLVHGNAGISRSAAFVIAYIMETFGMKYRDAFAYVQERRFCINPNAGFVHQLQEYEAIYLAKLTIQMMSPLQIERSLSVHSGTTGSLKRTHEEEDDPGTMQVATAQNGSEQ ID NO:31724 bpNOV 11b,ACTCTCCCACCCCACCCACCAGAATGGCGGGCCAGCACCATGGAGGACGTGAAGCTGGCG58564-02 DNA SequenceAGTTCCCTTCCCTTCCACAGTGCAAGGAAGACGCCGAGGAGTGGACCTACCCTATGAGACGAGAGATGCAGGAAATTTTATCTGGATTGTTCTTAGGCCCATATTCATCTGCTATGAAAAGCAAGCTACCTGTACTACAGAAACATGGAATAACCCATATAATATGCATACGACAAAATATTGAAGCAAACTTTATTAAACCAAACTTTCAGCAGTTATTTAGATATTTAGTCCTGGATATTGCAGATAATCCAGTTGAAAATATAATACGTTTTTTCCCTATGACTAAGGAATTTATTGATGGGAGCTTACAAATGGGAGGAAAAGTTCTTGTGCATGGAAATGCAGGGATCTCCAGAAGTGCAGCCTTTGTTATTGCATACATTATGGAAACATTTGGAATGAAGTACAGAGATGCTTTTGCTTATGTTCAAGAAAGAAGATTTTGTATTAATCCTAATGCTGGATTTGTCCATCAACTTCAGGAATATGAAGCCATCTACCTAGCAAAATTAACAATACAGATGATGTCACCACTCCAGATAGAAAGGTCATTATCTGTTCATTCTGGTACCACAGGCAGTTTGAAGAGAACACATGAAGAAGAGGATGATTTTGGAACCATGCAAGTGGCGACTGCACAGAATGGTGACTTGAAGAGCAACORF Start: ATG at 40ORF Stop: TGA at 709SEQ ID NO:32223 aaMW at 25482.1 kDNOV11b,MEDVKLEFPSLPQCKEDAEEWTYPMRREMQEILSGLFLGPYSSAMKSKLPVLQKHGITCG58564-02 Protein SequenceHIICIRQNIEANFIKPNFQQLFRYLVLDIADNPVENIIRFFPMTKEFIDGSLQMGGKVLVHGNAGISRSAAFVIAYIMETFGMKYRDAFAYVQERRFCINPNAGFVHQLQEYEAIYLAKLTIQMMSPLQIERSLSVHSGTTGSLKRTHEEEDDFGTMQVATAQNGSEQ ID NO:33545 bpNOV11c,ACTCTCCCACCCCACCCACCAGCCCGCGGGCCAGCACCATGGAGGACGTGAAGCTGGACG58564-03 DNA SequenceGTTCCCTTCCCTTCCACAGTGCAAGGAAGACGCCGAGGAGTGGACCTACCCTATGAGACGAGAGATGCAGGAAATTTTACCTGGATTGTTCTTAGGCCCATATTCATCTGCTATGAAAAGCAAGCTACCTGTACTACAGAAACATTTGGAATGAAGTACAGAGATGCTTTTGCTTATGTTCAAGAAAGAAGATTTTGTATTAATCCTAATGCTGGATTTGTCCATCAACTTCAGGAATATGAAGCCATCTACCTAGCAAAATTAACAATACAGATGATGTCACCACTCCAGATAGAAAGGTCATTATCTGTTCATTCTGGTACCACAGGCAGTTTGAAGAGAACACATGAGGAAGAGGATGATTTTGGAACCATGCAAGTGGCGACTGCACAGAATGGCTGACTTGAAGAGCAACATCATAGAGTGTGAATTTCTATTTGGGAAGGAGAAAATACAAGAGAAAATTATAATGTAAAATGGTAAAAAAORF Start: ATG at 39ORF Stop: TGA at 210SEQ ID NO:3457 aaMW at 6695.7 kDNOV11c,MEDVKLEFPSLPQCKEDAEEWTYPMRREMQEILPGLFLGPYSSAMKSKLPVLQKHLECG58564-03 DNA SequenceSEQ ID NO:35663 bpNOV11d,ACTCTCCCACCCCACCCACCAGCCCGCGGGCCAGCACCATGGAGGACGTGAAGCTGGACG58564-04 DNA SequenceGTTCCCTTCCCTTCCACAGTGCAAGGAAGACGCCGAGGAGTGGACCTACCCTATGAGACGAGAGATGCAGGAAATTTTACCTGGATTGTTCTTAGGCCCATATTCATCTGCTATGAAAAGCAAGCTACCTGTACTACAGAAACATGGAATAACCCATATAATATGCATACGACAAAATATTGAAGCAAACTTTATTAAACCAAACTTTCAGCAGTTATTTAGACTAAGGAATTTATTGATGGGAGCTTACAAATGGGAGGAAAAGTTCTTGTGCATGGAAATGCAGGGATCTCCAGAAGTGCAGCCTTTGTTATTGCATACATTATGGAAACATTTGGAATGAAGTACAGAGATGCTTTTGCTTATGTTCAAGAAAGAAGATTTTGTATTAATCCTAATGCTGGATTTGTCCATCAACTTCAGGAATATGAAGCCATCTACCTAGCAAAATTAACAATACAGATGATGTCACCACTCCAGATAGAAAGGTCATTATCTGTTCATTCTGGTACCACAGGCAGTTTGAAGAGAACACATGAAGAAGAGGATGATTTTGGAACCATGCAAGTGGCGACTGCACAGAATGGCTGACTTGAAGAGCAACTORF Start: ATG at 39ORF Stop: TGA at 399SEQ ID NO:36120 aaMW at 14245.6 kDNOV11d,MEDVKLEFPSLPQCKEDAEEWTYPMRREMQEILPGLFLGPYSSAMKSKLPVLQKHGITCG58564-04 Protein SequenceHIICIRQNIEANFIKPNFQQLEFRLRNLLMGAYKWEEKFLCMEMQGSPEVQPLLLHTLWKHLE


[0379] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 11B.
56TABLE 11BComparison of NOV11a against NOV11b through NOV11d.Identities/NOV11a Residues/Similarities forProtein SequenceMatch Residuesthe Matched RegionNOV11b1 . . . 223222/223(99%)1 . . . 223222/223(99%)NOV11c1 . . . 55 55/55(100%)1 . . . 55 55/55(100%)NOV11d1 . . . 81 81/81(100%)1 . . . 81 81/81(100%)


[0380] Further analysis of the NOV11a protein yielded the following properties shown in Table 11C.
57TABLE 11CProtein Sequence Properties NOV11aPSort0.4698 probability located in microbody (peroxisome); 0.4500analysis:probability located in cytoplasm; 0.1958 probability located inlysosome (lumen); 0.1000 probability located in mitochondrialmatrix spaceSignalPNo Known Signal Sequence Predictedanalysis:


[0381] A search of the NOV11a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 11D.
58TABLE 11DGeneseq Results for NOV11aIdentities/NOV11aSimilaritiesProtein/Residues/for theGeneseqOrganism/LengthMatchMatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAU09017Human dual 1 . . . 223223/223e−128specificity(100%)phosphatase 1 . . . 223223/22338692—Homo(100%)sapiens, 223 aa.[WO200173059-A2, Oct. 4, 2001]AAE08552Human 1 . . . 223223/223e−128phosphatase(100%)protein—Homo 1 . . . 223223/223sapiens, 223 aa.(100%)[WO200160992-A2, Aug. 23,2001]AAM41520Human poly- 1 . . . 223223/223e−128peptide SEQ ID(100%)NO 6451—Homo14 . . . 236223/223sapiens, 236 aa.(100%)[WO200153312-A1, Jul. 26, 2001]AAM39734Human poly- 1 . . . 223223/223e−128peptide SEQ ID(100%)NO 2879—Homo 1 . . . 223223/223sapiens, 223 aa.(100%)[WO200153312-A1, Jul. 26, 2001]AAU23521Novel human25 . . . 171 55/1471e−18 enzyme poly- (37%)peptide #607— 7 . . . 145 80/147Homo sapiens, (54%)190 aa.[WO200155301-A2, Aug. 2,2001]


[0382] In a BLAST search of public sequence databases, the NOV11a protein was found to have homology to the proteins shown in the BLASTP data in Table 11E.
59TABLE 11EPublic BLASTP Results for NOV11aIdentities/NOV11aSimilaritiesProteinResidues/for theAccessionProtein/MatchMatchedExpectNumberOrganism/LengthResiduesPortionValueCAD10219SEQUENCE 4 1 . . . 223223/223e−127FROM PATENT(100%) WO0173059— 1 . . . 223223/223Homo sapiens(100%) (Human), 223 aa.Q9DCF80610039A20RIK 1 . . . 223215/223e−124PROTEIN—Mus(96%)musculus 1 . . . 223221/223(Mouse), 223 aa.(98%)Q60970PROTEIN 1 . . . 223214/223e−124TYROSINE(95%)PHOSPHATASE- 1 . . . 223221/223LIKE—Mus(98%)musculus(Mouse), 223 aa.Q60969PROTEIN 1 . . . 168163/1682e−93 TYROSINE(97%)PHOSPHATASE- 1 . . . 168167/168LIKE—Mus(99%)musculus(Mouse), 205 aa.Q99850TYROSINE116 . . . 18166/663e−31 PHOSPHATASE-(100%) LIKE PROTEIN 1 . . . 6666/66HOMOLOG(100%) HSTYXB—Homo sapiens(Human), 66 aa(fragment).


[0383] PFam analysis predicts that the NOV11a protein contains the domains shown in the Table 11F.
60TABLE 11FDomain Analysis of NOV11aIdentities/NOV11aSimilarities forExpectPfam DomainMatch Regionthe Matched RegionValueDSPc: domain28 . . . 173 64/172 (37%)2.2e−631 of 1127/172 (74%)Y_phosphatase:35 . . . 179 35/279 (13%)1.7domain 1 of 1 93/279 (33%)



Example 12

[0384] The NOV12 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 12A.
61TABLE 12ANOV12 Sequence AnalysisSEQ ID NO:373696 bpNOV12a,GTGTAAAAATACTGTCCATTTAATGTTTTCTGGGACTTTAGGTAAGAATATGAAAACTCG57819-01 DNA SequenceCAACCACCCTTGAGCAGGATGAACCGGGAGGAATTGGAGGACAGTTTCTTTCGACTTCGCGAAGATCACATGTTGGTGAAGGAGCTTTCTTGGAAGCAACAGGATGAGATCAAAAGGCTGAGGACCACCTTGCTGCGGTTGACCGCTGCTGGCCGGGACCTGCGGGTCGCGGAGGAGGCGGCGCCGCTCTCGGAGACCGCAAGGCGCGGGCAGAAGGCGGGATGGCGGCAGCGCCTCTCCATGCACCAGCGCCCCCAGATGCACCGACTGCAAGGGCATTTCCACTGCGTCGGCCCTGCCAGCCCCCGCCGCGCCCAGCCTCGCGTCCAAGTGGGACACAGACAGCTCCACACAGCCGGTGCACCGGTGCCGGAGAAACCCAAGAGGGGTAGGGACAGGCTGAGCTACACAGCCCCTCCATCGTTTAAGGAGCATGCGACAAATGAAAACAGAGGTGAAGTAGCCAGTAAACCCAGTGAACTGGCCCACATCATGGCCAGCAATACCATGCAAGTGGAAGAGCCACCCAAGTCTCCTGAGAAAATGTGGCCTAAAGATGAAAATTTTGAACAGAGAAGCTCATTGGAGTGTGCTCAGAAGGCTGCAGAGCTTCGGGCTTCCATTAAAGAGAAGGTAGAGCTGATTCGACTTAAGAAGCTCTTACATGAAAGAAATGCTTCATTGGTTATGACAAAAGCACAATTAACAGAAGTTCAAGAGGTGAGTTGCCATCTTTTGACCCAGAATCAGGGAATCCTGAGTGCAGCCCATGAGGCCCTCCTCAAGCAAGTGAATGAGCTCAGGGCAGAGCTGAAGGAAGAAAGCAAGAAGGCTGTGAGCTTGAAGAGCCAACTGGAAGATGTGTCTATCTTGCAGATGACTCTGAAGGAGTTTCAGGAGAGAGTTGAAGATTTGGAAAAAGAACGAAAATTGCTGAATGACAATTATGACAAACTCTTAGAAAGCAGTGACAGCTCCAGTCAGCCCCACTGGAGCAACGAGCTCATAGCGGAACAGCTACAGCAGCAAGTCTCTCAGCTGCAGGATCAGCTGGATGCTGAGCTGGAGGACAAGAGAAAAGTTTTACTTGAGCTGTCCAGGGAGAAAGCCCAAAATGAGGATCTGAAGCTTGAAGTCACCAACATACTTCAGAAGCATAAACAGGAAGTAGAGCTCCTCCAAAATGCAGCCACAATTTCCCAACCTCCTGACAGGCAATCTGAACCAGCCACTCACCCAGCTGTATTGCAAGAGAACACTCAGATCCAGCCAAGTGAACCCAAAAACCAAGAAGAAAAGAAACTGTCCCAGGTGCTAAATGAGTTGCAAGTATCACACGCAGAGACCACATTGGAACTAGAAAAGACCAGGGACATGCTTATTCTGCAGCGCAAAATCAACGTGTGTTATCAGGAGGAACTGGAGGCAATGATGACAAAAGCTGACAATGATAATAGAGATCACAAAGAAAAGCTGGAGAGGTTGACTCGACTACTAGACCTCAAGAATAACCGTATCAAGCAGCTGGAAGAACAGCTCAAAGATGTTGCTTATGGCACCCGACCGTTGTCGTTATGTTTGGAAACACTGCCAGCCCATGGAGATGAGGATAAAGTGGATATTTCTCTGCTGCATCAGGGTGAGAATCTTTTTGAACTGCACATCCACCAGGCCTTCCTGACATCTGCCGCCCTAGCTCAGGCTGGAGATACCCAACCTACCACTTTCTGCACCTATTCCTTCTATGACTTTGAAACCCACTGTACCCCATTATCTGTGGGGCCACAGCCCCTCTATGACTTCACCTCCCAGTATGTGATGGAGACAGATTCGCTTTTCTTACACTACCTTCAAGAGGCTTCAGCCCGGCTTGACATACACCAGGCCATGGCCAGTGAACACAGCACTCTTGCTGCAGGATGGATTTGCTTTGACAGGGTGCTAGAGACTGTGGAGAAAGTCCATGGCTTGGCCACACTGATTGGTGCTGGTGGAGAAGAGTTCGGGGTTCTAGAGTACTGGATGAGGCTGCGTTTCCCCATAAAACCCAGCCTACAGGCGTGCAATAAACGAAAGAAAGCCCAGGTCTACCTGTCAACCGATGTGCTTGGAGGCCGGAAGGCCCAGGAAGAGGAGGTGAGATCGGAGTCTTGGGAACCTCAGAACGAGCTGTGGATTGAAATCACCAAGTGCTGTGGCCTCCGGAGTCGATGGCTGGGAACTCAACCCAGTCCATATGCTGTGTACCGCTTCTTCACCTTTTCTGACCATGACACTGCCATCATTCCAGCCAGTAACAACCCCTACTTTAGAGACCAGGCTCGATTCCCAGTGCTTGTGACCTCTGACCTGGACCATTATCTGAGACGGGAGGCCTTGTCTATACATGTTTTTGATGATGAAGACTTAGAGCCTGGCTCGTATCTTGGCCGAGCCCGAGTGCCTTTACTGCCTCTTGCAAAAAATGAATCTATCAAAGGTGATTTTAACCTCACTGACCCTGCAGAGAAACCCAACGGATCTATTCAAGTGCAACTGGATTGGAAGTTTCCCTACATACCCCCTGAGAGCTTCCTGAAACCAGAAGCTCAGACTAAGGGGAAGGATACCAAGGACAGTTCAAAGATCTCATCTGAAGAGGAAAAGGCTTCATTTCCTTCCCAGGATCAGATGGCATCTCCTGAGGTTCCCATTGAAGCTGGCCAGTATCGATCTAAGAGAAAACCTCCTCATGGGGGAGAAAGAAAGGAGAAGGAGCACCAGGTTGTGAGCTACTCAAGAAGAAAACATGGCAAAAGAATAGGTGTTCAAGGAAAGAATAGAATGGAGTATCTTAGCCTTAACATCTTAAATGGAAATACACTGAAGCAGGTGAATTACACTGAGTGGAAGTTCTCAGAGACTAACAGCTTCATAGGTGATGGCTTTAAAAATCAGCACGAGGAAGAGGAAATGACATTATCCCATTCAGCACTGAAACAGAAGGAACCTCTACATCCTGTAAATGACAAAGAATCCTCTGAACAAGGTTCTGAAGTCAGTGAAGCACAAACTACCGACAGTGATGATGTCATAGTGCCACCCATGTCTCAGAAATATCCTAAGGCAGATTCAGAGAAGATGTGCATTGAAATTGTCTCCCTGGCCTTCTACCCAGAGGCAGAAGTGATGTCTGATGAGAACATAAAACAGGTGTATGTGGAGTACAAATTCTACGACCTACCCTTGTCGGAGACAGAGACTCCAGTGTCCCTAAGGAAGCCTAGGGCAGGAGAAGAAATCCACTTTCACTTTAGCAAGGTAATAGACCTGGACCCACAGGAGCAGCAAGGCCGAAGGCGGTTTCTGTTCGACATGCTGAATGGACAAGATCCTGATCAAGGACAGTTAAAGTTTACAGTGGTAAGTGATCCTCTGGATGAAGAAAAGAAAGAATGTGAAGAAGTGGGATATGCATATCTTCAACTGTGGCAGATCCTGGAGTCAGGAAGAGATATTCTAGAGCAAGAGCTAGACGTTGTTAGCCCTGAAGATCTGGCTACCCCAATAGGAAGGCTGAAGGTTTCCCTTCAAGCAGCTGCTGTCCTCCATGCTATTTACAAGGAGATGACTGAAGATTTGTTTTCATGAAGGAACAAORF Start: ATG at 23ORF Stop: TGA at 3686SEQ ID NO:381221 aaMW at 139825.2 kDNOV12a,MFSGTLGKNMKTQPPLSRMNREELEDSFFRLREDHMLVKELSWKQQDEIKRLRTTLLRCG57819-01 ProteinLTAAGRDLRVAEEAAPLSETARRGQKAGWRQRLSMHQRPQMHRLQGHFHCVGPASPRRAQPRVQVGHRQLHTAGAPVPEKPKRGRDRLSYTAPPSFKEHATNENRGEVASKPSELAHIMASNTMQVEEPPKSPEKMWPKDENFEQRSSLECAQKAAELRASIKEKVELIRLKKLLHERNASLVMTKAQLTEVQEVSCHLLTQNQGILSAAHEALLKQVNELRAELKEESKKAVSLKSQLEDVSILQMTLKEFQERVEDLEKERKLLNDNYDKLLESSDSSSQPHWSNELTAEQLQQQVSQLQDQLDAELEDKRKVLLELSREKAQNEDLKLEVTNILQKHKQEVELLQNAATISQPPDRQSEPATHPAVLQENTQIQPSEPKNQEEKKLSQVLNELQVSHAETTLELEKTRDMLILQRKINVCYQEELEAMMTKADNDNRDHKEKLERLTRLLDLKNNRIKQLEEQLKDVAYGTRPLSLCLETLPAHGDEDKVDISLLHQGENLFELHIHQAFLTSAALAQAGDTQPTTFCTYSFYDFETHCTPLSVGPQPLYDFTSQYVMETDSLFLHYLQEASARLDIHQAMASEHSTLAAGWICFDRVLETVEKVHGLATLIGAGGEEFGVLEYWMRLRFPIKPSLQACNKRKKAQVYLSTDVLGGRKAQEEEVRSESWEPQNELWIEITKCCGLRSRWLGTQPSPYAVYRFFTFSDHDTAIIPASNNPYFRDQARFPVLVTSDLDHYLRREALSIHVFDDEDLEPGSYLGRARVPLLPLAKNESIKGDFNLTDPAEKPNGSIQVQLDWKFPYIPPESFLKPEAQTKGKDTKDSSKISSEEEKASFPSQDQMASPEVPIEAGQYRSKRKPPHGGERKEKEHQVVSYSRRKHGKRIGVQGKNRMEYLSLNILNGNTLKQVNYTEWKFSETNSFIGDGFKNQHEEEEMTLSHSALKQKEPLHPVNDKESSEQGSEVSEAQTTDSDDVIVPPMSQKYPKADSEKMCIEIVSLAFYPEAEVMSDENIKQVYVEYKFYDLPLSETETPVSLRKPRAGEEIHFHFSKVIDLDPQEQQGRRRFLFDMLNGQDPDQGQLKFTVVSDPLDEEKKECEEVGYAYLQLWQILESGRDILEQELDVVSPEDLATPIGRLKVSLQAAAVLHAIYKEMTEDLFS


[0385] Further analysis of the NOV12a protein yielded the following properties shown in Table 12B.
62TABLE 12BProtein Sequence Properties NOV12aPSort0.9600 probability located in nucleus; 0.3000 probabilityanalysis:located in microbody (peroxisome); 0.1000 probability locatedin mitochondrial matrix space; 0.1000 probability located inlysosome (lumen)SignalPNo Known Signal Sequence Predictedanalysis:


[0386] A search of the NOV12a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 12C.
63TABLE 12CGeneseq Results for NOV12aIdentities/NOV12aSimilaritiesProtein/Residues/for theGeneseqOrganism/LengthMatchMatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAM78558Human protein63 . . . 1219400/1193 e−172SEQ ID NO(33%)1220—Homo47 . . . 1177640/1193sapiens, 1179 aa.(53%)[WO200157190-A2, Aug. 9,2001]AAM79542Human protein63 . . . 1219400/1193 e−172SEQ ID NO(33%)3188—Homo28 . . . 1158640/1193sapiens, 1160 aa.(53%)[WO200157190-A2, Aug. 9,2001]AAM41414Human poly-63 . . . 1219400/1193 e−172peptide SEQ ID(33%)NO 6345—Homo28 . . . 1158640/1193sapiens, 1160 aa.(53%)[WO200153312-A1, Jul. 26, 2001]AAM39628Human poly-118 . . . 1219 390/1138 e−171peptide SEQ ID(34%)NO 2773—Homo47 . . . 1126623/1138sapiens, 1128 aa.(54%)[WO200153312-A1, Jul. 26, 2001]AAG75661Human colon445 . . . 523 40/79 1e−13 cancer antigen(50%)protein SEQ ID33 . . . 111 56/79 NO:6425—Homo(70%)sapiens, 118 aa.[WO200122920-A2, Apr. 5, 2001]


[0387] In a BLAST search of public sequence databases, the NOV12a protein was found to have homology to the proteins shown in the BLASTP data in Table 12D.
64TABLE 12DPublic BLASTP Results for NOV12aIdentities/NOV12aSimilaritiesProteinResidues/for theAccessionProtein/MatchMatchedExpectNumberOrganism/LengthResiduesPortionValueQ96KN7RPGR- 7 . . . 12211203/12580.0INTERACTING(95%)PROTEIN 1—29 . . . 12861207/1258Homo sapiens(95%)(Human), 1286 aa.Q96QA8RPGR- 7 . . . 12211203/12580.0INTERACTING(95%)PROTEIN 1—29 . . . 12861207/1258Homo sapiens(95%)(Human), 1286 aa.Q9GLM3RPGR- 1 . . . 1221 922/12340.0INTERACTING(74%)PROTEIN-1— 1 . . . 12211031/1234Bos taurus(82%)(Bovine), 1221 aa.Q9NR40RPGR-331 . . . 1221 883/9020.0INTERACTING(97%)PROTEIN—1 . . . 902888/902Homo sapiens(97%)(Human), 902 aa.Q9HBK6RPGR-471 . . . 1221 742/7630.0INTERACTING(97%)PROTEIN-1—1 . . . 762746/763Homo sapiens(97%)(Human), 762 aa.


[0388] PFam analysis predicts that the NOV12a protein contains the domains shown in the Table 12E.
65TABLE 12EDomain Analysis of NOV12aNOV12aIdentities/SimilaritiesExpectPfam DomainMatch Regionfor the Matched RegionValuePFEMP: domain293 . . . 41323/176 (13%)7.91 of 182/176 (47%)C2: domain736 . . . 82514/101 (14%)1.41 of 154/101 (53%)



Example 13

[0389] The NOV13 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 13A.
66TABLE 13ANOV13 Sequence AnalysisSEQ ID NO:39678 bpNOV13a,TGGGGCGGGAGGCATGGTCTCCACCTACCGGGTGGCCGTGCTGGGGGCGCGAGGTGTGCG57789-01 DNA SequenceGGCAAGAGTGCCATCGTGCGCCAGTTCTTGTACAACGAGTTCAGCGAGGTCTGCGTCCCCACCACCGCCCGCCGCCTTTACCTGCCTGCTGTCGTCATGAACGGCCACGTGCACGACCTCCAGATCCTCGACTTTCCACCCATCAGCGCCTTCCCTGTCAATACGCTCCAGGAGTGGGCAGACACCTGCTGCAGGGGACTCCGGAGTGTCCACGCCTACATCCTGGTCTACGACATCTGCTGCTTTGACAGCTTTGAGTACGTCAAGACCATCCGCCAGCAGATCCTGGAGACGAGGGTGATCGGAACCTCAGAGACGCCCATCATCATCGTGGGCAACAAGCGGGACCTGCAGCGCGGACGCGTGATCCCGCGCTGGAACGTGTCGCACCTGGTACGCAAGACCTGGAAGTGCGGCTACGTGGAATGCTCGGCCAAGTACAACTGGCACATCCTGCTGCTCTTCAGCGAGCTGCTCAAGAGCGTCGGCTGCGCCCGTTGCAAGCACGTGCACGCTGCCCTGCGCTTCCAGGGCGCGCTGCGCCGCAACCGCTGCGCCATCATGTGACGCCTGCGCGCCCCTCGGGCTGCACCGGCACTGGCCGAGCGGAGGGCGGGGCCORF Start: ATG at 14ORF Stop: TGA at 623SEQ ID NO:40203 aaMW at 23229.0 kDNOV13a,MVSTYRVAVLGARGVGKSAIVRQFLYNEFSEVCVPTTARRLYLPAVVMNGHVHDLQILCG57789-01 Protein SequenceDFPPISAFPVNTLQEWADTCCRGLRSVHAYILVYDICCFDSFEYVKTIRQQILETRVIGTSETPIIIVGNKRDLQRGRVIPRWNVSHLVRKTWKCGYVECSAKYNWHILLLFSELLKSVGCARCKHVHAALRFQGALRRNRCAIMSEQ ID NO:41682 bpNOV13b,TGGGAGGCATGGTCTCCACCTACCGGGTGGCCGTGCTGGGGGCGCGAGGTGTGGGCAACG57789-02 DNA SequenceGAGTGCCATCGTGCGCCAGTTCTTGTACAACGAGTTCAGCGAGGTCTGCGTCCCCACCACCGCCCGCCGCCTTTACCTGCCTGCTGTCGTCATGAACGGCCACGTGCACGACCTCCAGATCCTCGACTTTCCACCCATCAGCGCCTTCCCTGTCAATACGCTCCAGGAGTGGGCAGACACCTGCTGCAGGGGACTCCGGAGTGTCCACGCCTACATCCTGGTCTACGACATCTGCTGCTTTGACAGCTTTGAGTACGTCAAGACCATCCGCCAGCAGATCCTGGAGACGAGGGTGATCGGAACCTCAGAGACGCCCATCATCATCGTGGGCAACAAGCGGGACCTGCAGCGCGGACGCGTGATCCCGCGCTGGAACGTGTCGCACCTGGTACGCAAGACCTGGAAGTGCGGCTACGTGGAATGCTCGGCCAAGTACAACTGGCACATCCTGCTGCTCTTCAGCGAGCTGCTCAAGAGCGTCGGCTGCGCCCGTTGCAAGCACGTGCACGCTGCCCTGCGCTTCCAGGGCGCGCTGCGCCGCAACCGCTGCGCCATCATGTGACGCCTGCGCGCCCCTCGGGCTGCACCGGCACTGGCCGAGCGGAGGGCACTGGCCGAGCGGAGORF Start: ATG at 9ORF Stop: TGA at 618SEQ ID NO:42203 aaMW at 23229.0 kDNOV13b,MVSTYRVAVLGARGVGKSAIVRQFLYNEFSEVCVPTTARRLYLPAVVMNGHVHDLQILCG57789-02 Protein SequenceDFPPISAFPVNTLQEWADTCCRGLRSVHAYILVYDICCFDSFEYVKTIRQQILETRVIGTSETPIIIVGNKRDLQRGRVIPRWNVSHLVRKTWKCGYVECSAKYNWHILLLFSELLKSVGCARCKHVHAALRFQGALRRNRCAIM


[0390] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 13B.
67TABLE 13BComparison of NOV13a against NOV13b.ProteinNOV13a Residues/Identities/SimilaritiesSequenceMatch Residuesfor the Matched RegionNOV13b1 . . . 203203/203 (100%)1 . . . 203203/203 (100%)


[0391] Further analysis of the NOV13a protein yielded the following properties shown in Table 13C.
68TABLE 13CProtein Sequence Properties NOV13aPSort0.6500 probability located in plasma membrane; 0.5064analysis:probability located in mitochondrial matrix space; 0.3844probability located in microbody (peroxisome); 0.2556probability located in lysosome (lumen)SignalPNo Known Signal Sequence Predictedanalysis:


[0392] A search of the NOV13a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 13D.
69TABLE 13DGeneseq Results for NOV13aIdentities/NOV13aSimilaritiesProtein/Residues/for theGeneseqOrganism/LengthMatchMatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAB42840Human ORFX1 . . . 136136/1362e−75ORF2604 poly-(100%) peptide sequence1 . . . 136136/136SEQ ID NO:5208—(100%) Homo sapiens,136 aa.[WO200058473-A2,Oct. 5, 2000]AAM41682Human polypeptide5 . . . 174 66/1714e−18SEQ ID NO 6613—(38%)Homo sapiens,15 . . . 173 189/171206 aa.(51%)[WO200153312-A1,Jul. 26, 2001]AAM39896Human polypeptide5 . . . 174 66/1714e−18SEQ ID NO 3041—(38%)Homo sapiens,8 . . . 166 89/171199 aa.(51%)[WO200153312-A1,Jul. 26, 2001]AAY99656Human GTPase5 . . . 173 59/1793e−14associated protein-(32%)7—Homo sapiens,25 . . . 191  87/179281 aa.(47%)WO200031263-A2,Jun. 2, 2000]AAR05075RAP1A Gene5 . . . 177 57/1755e-14product(32%)incorporating at4 . . . 165 90/175least one peptide(50%)associated with rasoncogene—Synthetic, 184 aa.[WO9000179-A,Jan. 11, 1990]


[0393] In a BLAST search of public sequence databases, the NOV13a protein was found to have homology to the proteins shown in the BLASTP data in Table 13E.
70TABLE 13EPublic BLASTP Results for NOV13aNOV13aIdentities/ProteinResidues/SimilaritiesAccessionProtein/Matchfor theExpectNumberOrganism/LengthResiduesMatched PortionValueQ96S79RAS-LIKE1 . . . 203203/203 (100%) e−118PROTEIN/1 . . . 203203/203 (100%)VTS58635—Homo sapiens(Human), 203 aa.Q92737Ras-like protein1 . . . 203105/204 (51%) 3e−50 RRP22 (RAS-1 . . . 203134/204 (65%) related proteinon chromosome22)—Homosapiens (Human),203 aa.Q95KD9HYPO-5 . . . 17466/171 (38%)1e−17 THETICAL8 . . . 16689/171 (51%)22.5 KDAPROTEIN—Macacafascicularis(Crab eatingmacaque)(Cynomolgusmonkey), 199 aa.Q96HU8SIMILAR TO5 . . . 17466/171 (38%)1e−17 CG8500 GENE8 . . . 16689/171 (51%)PRODUCT—Homo sapiens(Human), 199 aa.Q9NF75EG:BACR37P7.85 . . . 17461/174 (35%)4e−16 PROTEIN—48 . . . 210 88/174 (50%)Drosophilamelanogaster(Fruit fly),306 aa.


[0394] PFam analysis predicts that the NOV13a protein contains the domains shown in the Table 13F.
71TABLE 13FDomain Analysis of NOV13aNOV13aIdentities/SimilaritiesExpectPfam DomainMatch Regionfor the Matched RegionValueSemialdhyde_dh:4 . . . 14  4/11 (36%)0.75domain 1 of 1 11/11 (100%)ras: domain 1 of 16 . . . 20356/224 (25%)1.2e−12125/224 (56%) 



Example 14

[0395] The NOV14 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 14A.
72TABLE 14ANOV14 Sequence AnalysisSEQ ID NO:431790 bpNOV14a,TCTCCCTCCCGCGCGATGGCCTCGGCGCTGAGCTATGTCTCCAAGTTCAAGTCCTTCGCG57758-01 DNA SequenceTGATCTTGTTCGTCACCCCGCTCCTGCTGCTGCCACTCGTCATTCTGATGCCCGCCAAGGTCAGTTGTGCCTACGTCATCATCCTCATGGCCATTTACTGGTGCACAGAAGTCATCCCTCTGGCTGTCACCTCTCTCATGCCTGTCTTGCTTTTCCCACTCTTCCAGATTCTGGACTCCAGGCAGGTGTGTGTCCAGTACATGAAGGACACCAACATGCTGTTCCTGGGCGGCCTCATCGTGGCCGTGGCTGTGGAGCGCTGGAACCTGCACAAGAGGATCGCCCTGCGCACGCTCCTCTGGGTGGGGGCCAAGCCTGCACGGCTGATGCTGGGCTTCATGGGCGTCACAGCCCTCCTGTCCATGTGGATCAGTAACACGGCAACCACGGCCATGATGGTGCCCATCGTGGAGGCCATATTGCAGCAGATGGAAGCCACAAGCGCAGCCACCGAGGCCGGCCTGGAGCTGGTGGACAAGGGCAAGGCCAAGGAGCTGCCAGGGAGTCAAGTGATTTTTGAAGGCCCCACTCTGGGGCAGCAGGAAGACCAAGAGCGGAAGAGGTTGTGTAAGGCCATGACCCTGTGCATCTGCTACGCGGCCAGCATCGGGGGCACCGCCACCCTGACCGGGACGGGACCCAACGTGGTGCTCCTGGGCCAGATGAACGAGTTGTTTCCTGACAGCAAGGACCTCGTGAACTTTGCTTCCTGGTTTGCATTTGCCTTTCCCAACATGCTGGTGATGCTGCTGTTCGCCTGGCTGTGGCTCCAGTTTGTTTACATGTTCTCCAGTTTTAAAAAGTCCTGGGGCTGCGGGCTAGAGAGCAAGAAAAACGAGAAGGCTGCCCTCAAGGTGCTGCAGGAGGAGTACCGGAAGCTGGGGCCCTTGTCCTTCGCGGAGATCAACGTGCTGATCTGCTTCTTCCTGCTGGTCATCCTGTGGTTCTCCCGAGACCCCGGCTTCATGCCCGGCTGGCTGACTGTTGCCTGGGTGGAGGGTGAGACAAAGTATGTCTCCGATGCCACTGTGGCCATCTTTGTGGCCACCCTGCTATTCATTGTGCCTTCACAGAAGCCCAAGTTTAACTTCCGCAGCCAGACTGAGGAAGGTAAGTCTCCTGTTCTGATCGCCCCCCCTCCCCTGCTGGATTGGAAGGTAACCCAGGAGAAAGTGCCCTGGGGCATCGTGCTGCTACTAGGGGGCGGATTTGCTCTGGCTAAAGGATCCGAGGCCTCGGGGCTGTCCGTGTGGATGGGGAAGCAGATGGAGCCCTTGCACGCAGTGCCCCCGGCAGCCATCACCTTGATCTTGTCCTTGCTCGTTGCCGTGTTCACTGAGTGCACAAGCAACGTGGCCACCACCACCTTGTTCCTGCCCATCTTTGCCTCCATGTCTCGCTCCATCGGCCTCAATCCGCTGTACATCATGCTGCCCTGTACCCTGAGTGCCTCCTTTGCCTTCATGTTGCCTGTGGCCACCCCTCCAAATGCCATCGTGTTCACCTATGGGCACCTCAAGGTTGCTGACATGGTGAAAACAGGAGTCATAATGAACATAATTGGAGTCTTCTGTGTGTTTTTGGCTGTCAACACCTGGGGACGGGCCATATTTGACTTGGATCATTTCCCTGACTGGGCTAATGTGACACATATTGAGACTTAGGAAGAGCCACAAGACCACACACACAGCCCTTACCCTCCTCAGGACTACCGAACCTTCTGGCACACCTTORF Start: ATG at 16ORF Stop: TAG at 1720SEQ ID NO:44568 aaMW at 62592.9 kDNOV14a,MASALSYVSKFKSFVILFVTPLLLLPLVILMPAKVSCAYVIILMAIYWCTEVIPLAVTCG57758-01 Protein SequenceSLMPVLLFPLFQILDSRQVCVQYMKDTNMLFLGGLIVAVAVERWNLHKRIALRTLLWVGAKPARLMLGFMGVTALLSMWISNTATTAMMVPIVEAILQQMEATSAATEAGLELVDKGKAKELPGSQVIFEGPTLGQQEDQERKRLCKAMTLCICYAASIGGTATLTGTGPNVVLLGQMNELFPDSKDLVNFASWFAFAFPNMLVMLLFAWLWLQFVYMFSSFKKSWGCGLESKKNEKAALKVLQEEYRKLGPLSFAEINVLICFFLLVILWFSRDPGFMPGWLTVAWVEGETKYVSDATVAIFVATLLFIVPSQKPKFNFRSQTEEGKSPVLIAPPPLLDWKVTQEKVPWGIVLLLGGGFALAKGSEASGLSVWMGKQMEPLHAVPPAAITLILSLLVAVFTECTSNVATTTLFLPIFASMSRSIGLNPLYIMLPCTLSASFAFMLPVATPPNAIVFTYGHLKVADMVKTGVIMNIIGVFCVFLAVNTWGRAIFDLDHFPDWANVTHIETSEQ ID NO:451899 bpNOV14b,CGTCTCGCCCGCCAGTCTCCCTCCCGCGCGATGGCCTCGGCGCTGAGCTATGTCTCCACG57758-02 DNA SequenceAGTTCAAGTCCTTCGTGATCTTGTTCGTCACCCCGCTCCTGCTGCTGCCACTCGTCATTCTGATGCCCGCCAAGGTCAGTTGCTGTGCCTACGTCATCATCCTCATGGCCATTTACTGGTGCACAGAAGTCATCCCTCTGGCTGTCACCTCTCTCATGCCTGTCTTGCTTTTCCCACTCTTCCAGATTCTGGACTCCAGGCAGGTGTGTGTCCAGTACATGAAGGACACCAACATGCTGTTCCTGGGCGGCCTCATCGTGGCCGTGGCTGTGGAGCGCTGGAACCTGCACAAGAGGATCGCCCTGCGCACGCTCCTCTGGGTGGGGGCCAAGCCTGCACGGCTGATGCTGGGCTTCATGGGCGTCACAGCCCTCCTGTCCATGTGGATCAGTAACACGGCAACCACGGCCATGATGGTGCCCATCGTGGAGGCCATATTGCAGCAGATGGAAGCCACAAGCGCAGCCACCGAGGCCGGCCTGGAGGGACAAGGTACCACAATAAACAACCTGAATGCACTGGAGGATGATACAGTGAAAGCAGTACTAGGAGGAAAGTGTGTAGCTATAATAAGCACTTACGTCAAAAAAGTAGAAAAACTTCAAATAAACAATCTAATGACACCTCTTAAAAAACTAGAAAAGCAAGAGCAACAGGACCTAGGGCCTGGCATCAGGCCTCAGGACTCTGCCCAGTGCCAGGAAGACCAAGAGCGGAAGAGGTTGTGTAAGGCCATGACCCTGTGCATCTGCTACGCGGCCAGCATCGGGGGCACCGCCACCCTGACCGGGACGGGACCCAACGTGGTGCTCCTGGGCCAGATGAACGAGTTGTTTCCTGACAGCAAGGACCTCGTGAACTTTGCTTCCTGGTTTGCATTTGCCTTTCCCAACATGCTGGTGATGCTGCTGTTCGCCTGGCTGTGGCTCCAGTTTGTTTACATGTTCTCCAGTTTTAAAAAGTCCTGGGGCTGCGGGCTAGAGAGCAAGAAAAACGAGAAGGCTGCCCTCAAGGTGCTGCAGGAGGAGTACCGGAAGCTGGGGCCCTTGTCCTTCGCGGAGATCAACGTGCTGATCTGCTTCTTCCTGCTGGTCATCCTGTGGTTCTCCCGAGACCCCGGCTTCATGCCCGGCTGGCTGACTGTTGCCTGGGTGGAGGGTGAGACAAAGTCAGTCTCCGATGCCACTGTGGCCATCTTTGTGGCCACCCTGCTATTCATTGTGCCTTCACAGAAGCCCAAGTTTAACTTCCGCAGCCAGACTGAGGAAGGTAAGTCTCCTGTTCTGATCGCCCCCCCTCCCCTGCTGGATTGGAAGGTAACCCAGGAGAAAGTGCCCTGGGGCATCGTGCTGCTACTAGGGGGCGGATTTGCTCTGGCTAAAGGATCCGAGGCCTCGGGGCTGTCCGTGTGGATGGGGAAGCAGATGGAGCCCTTGCACGCAGTGCCCCCGGCAGCCATCACCTTGATCTTGTCCTTGCTCGTTGCCGTGTTCACTGAGTGCACAAGCAACGTGGCCACCACCACCTTGTTCCTGCCCATCTTTGCCTCCATGTCTCGCTCCATCGGCCTCAATCCGCTGTACATCATGCTGCCCTGTACCCTGAGTGCCTCCTTTGCCTTCATGTTGCCTGTGGCCACCCCTCCAAATGCCATCGTGTTCACCTATGGGCACCTCAAGGTTGCTGACATGGTAAAAACAGGAGTCATAATGAACATAATTGGAGTCTTCTGTGTGTTTTTGGCTGTCAACACCTGGGGACGGGCCATATTTGACTTGGATCATTTCCCTGACTGGGCTAATGTGACACATATTGAGACTTAGGAAGAGCCACAAGACCACORF Start: ATG at 31ORF Stop: TAG at 1879SEQ ID NO:46616 aaMW at 67816.9 kDNOV14b,MASALSYVSKFKSFVILFVTPLLLLPLVILMPAKVSCCAYVIILMAIYWCTEVIPLAVCG57758-02 Protein SequenceTSLMPVLLFPLFQILDSRQVCVQYMKDTNMLFLGGLIVAVAVERWNLHKRIALRTLLWVGAKPARLMLGFMGVTALLSMWISNTATTAMMVPIVEAILQQMEATSAATEAGLEGQGTTINNLNALEDDTVKAVLGGKCVAIISTYVKKVEKLQINNLMTPLKKLEKQEQQDLGPGIRPQDSAQCQEDQERKRLCKAMTLCICYAASIGGTATLTGTGPNVVLLGQMNELFPDSKDLVNFASWFAFAFPNMLVMLLFAWLWLQFVYMFSSFKKSWGCGLESKKNEKAALKVLQEEYRKLGPLSFAEINVLICFFLLVILWFSRDPGFMPGWLTVAWVEGETKSVSDATVAIFVATLLFIVPSQKPKFNFRSQTEEGKSPVLIAPPPLLDWKVTQEKVPWGIVLLLGGGFALAKGSEASGLSVWMGKQMEPLHAVPPAAITLILSLLVAVFTECTSNVATTTLFLPIFASMSRSIGLNPLYIMLPCTLSASFAFMLPVATPPNAIVFTYGHLKVADMVKTGVIMNIIGVFCVFLAVNTWGRAIFDLDHFPDWANVTHIETSEQ ID NO:471899 bpNOV14c,CGTCTCGCCCGCCAGTCTCCCTCCCGCGCGATGGCCTCGGCGCTGAGCTATGTCTCCACG57758-03 DNA SequenceAGTTCAAGTCCTTCGTGATCTTGTTCGTCACCCCGCTCCTGCTGCTGCCACTCGTCATTCTGATGCCCGCCAAGGTCAGTTGCTGTGCCTACGTCATCATCCTCATGGCCATTTACTGGTGCACAGAAGTCATCCCTCTGGCTGTCACCTCTCTCATGCCTGTCTTGCTTTTCCCACTCTTCCAGATTCTGGACTCCAGGCAGGTGTGTGTCCAGTACATGAAGGACACCAACATGCTGTTCCTGGGCGGCCTCATCGTGGCCGTGGCTGTGGAGCGCTGGAACCTGCACAAGAGGATCGCCCTGCGCACGCTCCTCTGGGTGGGGGCCAAGCCTGCACGGCTGATGCTGGGCTTCATGGGCGTCACAGCCCTCCTGTCCATGTGGATCAGTAACACGGCAACCACGGCCATGATGGTGCCCATCGTGGAGGCCATATTGCAGCAGATGGAAGCCACAAGCGCAGCCACCGAGGCCGGCCTGGAGGGACAAGGTACCACAATAAACAACCTGAATGCACTGGAGGATGATACAGTGAAAGCAGTACTAGGAGGAAAGTGTGTAGCTATAATAAGCACTTACGTCAAAAAAGTAGAAAAACTTCAAATAAACAATCTAATGACACCTCTTAAAAAACTAGAAAAGCAAGAGCAACAGGACCTAGGGCCTGGCATCAGGCCTCAGGACTCTGCCCAGTGCCAGGAAGACCAAGAGCGGAAGAGGTTGTGTAAGGCCATGACCCTGTGCATCTGCTACGCGGCCAGCATCGGGGGCACCGCCACCCTGACCGGGACGGGACCCAACGTGGTGCTCCTGGGCCAGATGAACGAGTTGTTTCCTGACAGCAAGGACCTCGTGAACTTTGCTTCCTGGTTTGCATTTGCCTTTCCCAACATGCTGGTGATGCTGCTGTTCGCCTGGCTGTGGCTCCAGTTTGTTTACATGTTCTCCAGTTTTAAAAAGTCCTGGGGCTGCGGGCTAGAGAGCAAGAAAAACGAGAAGGCTGCCCTCAAGGTGCTGCAGGAGGAGTACCGGAAGCTGGGGCCCTTGTCCTTCGCGGAGATCAACGTGCTGATCTGCTTCTTCCTGCTGGTCATCCTGTGGTTCTCCCGAGACCCCGGCTTCATGCCCGGCTGGCTGACTGTTGCCTGGGTGGAGGGTGAGACAAAGTCAGTCTCCGATGCCACTGTGGCCATCTTTGTGGCCACCCTGCTATTCATTGTGCCTTCACAGAAGCCCAAGTTTAACTTCCGCAGCCAGACTGAGGAAGGTAAGTCTCCTGTTCTGATCGCCCCCCCTCCCCTGCTGGATTGGAAGGTAACCCAGGAGAAAGTGCCCTGGGGCATCGTGCTGCTACTAGGGGGCGGATTTGCTCTGGCTAAAGGATCCGAGGCCTCGGGGCTGTCCGTGTGGATGGGGAAGCAGATGGAGCCCTTGCACGCAGTGCCCCCGGCAGCCATCACCTTGATCTTGTCCTTGCTCGTTGCCGTGTTCACTGAGTGCACAAGCAACGTGGCCACCACCACCTTGTTCCTGCCCATCTTTGCCTCCATGTCTCGCTCCATCGGCCTCAATCCGCTGTACATCATGCTGCCCTGTACCCTGAGTGCCTCCTTTGCCTTCATGTTGCCTGTGGCCACCCCTCCAAATGCCATCGTGTTCACCTATGGGCACCTCAAGGTTGCTGACATGGTAAAAACAGGAGTCATAATGAACATAATTGGAGTCTTCTGTGTGTTTTTGGCTGTCAACACCTGGGGACGGGCCATATTTGACTTGGATCATTTCCCTGACTGGGCTAATGTGACACATATTGAGACTTAGGAAGAGCCACAAGACCACORF Start: ATG at 31ORF Stop: TAG at 1879SEQ ID NO:48616 aaMW at 67816.9 kDNOV14c,MASALSYVSKFKSFVILFVTPLLLLPLVILMPAKVSCCAYVIILMAIYWCTEVIPLAVCG57758-03 Protein SequenceTSLMPVLLFPLFQILDSRQVCVQYMKDTNMLFLGGLIVAVAVERWNLHKRIALRTLLWVGAKPARLMLGFMGVTALLSMWISNTATTAMMVPIVEAILQQMEATSAATEAGLEGQGTTINNLNALEDDTVKAVLGGKCVAIISTYVKKVEKLQINNLMTPLKKLEKQEQQDLGPGIRPQDSAQCQEDQERKRLCKAMTLCICYAASIGGTATLTGTGPNVVLLGQMNELFPDSKDLVNFASWFAFAFPNMLVMLLFAWLWLQFVYMFSSFKKSWGCGLESKKNEKAALKVLQEEYRKLGPLSFAEINVLICFFLLVILWFSRDPGFMPGWLTVAWVEGETKSVSDATVAIFVATLLFIVPSQKPKFNFRSQTEEGKSPVLIAPPPLLDWKVTQEKVPWGIVLLLGGGFALAKGSEASGLSVWMGKQMEPLHAVPPAAITLILSLLVAVFTECTSNVATTTLFLPIFASMSRSIGLNPLYIMLPCTLSASFAFMLPVATPPNAIVFTYGHLKVADMVKTGVIMNIIGVFCVFLAVNTWGRAIFDLDHFPDWANVTHIETSEQ ID NO:491606 bpNOV14d,GATGGCCTCGGCGCTGAGCTATGTCTCCAAGTTCAAGTCCTTCGTGATCTTGTTCGTCCG57758-04 DNA SequenceACCCCGCTCCTGCTGCTGCCACTCGTCATTCTGATGCCCGCCAAGTTTGTCAGGTGTGCCTACGTCATCATCCTCATGGCCATTTACTGGTGCACAGAAGTCATCCCTCTGGCTGTCACCTCTCTCATGCCTGTCTTGCTTTTCCCACTCTTCCAGATTCTGGACTCCAGGCAGGTGTGTGTCCAGTACATGAAGGACACCAACATGCTGTTCCTGGGCGGCCTCATCGTGGCCGTGGCTGTGGAGCGCTGGAACCTGCACAAGAGGATCGCCCTGCGCACGCTCCTCTGGGTGGGGGCCAAGCCTGCACGGCTGATGCTGGGCTTCATGGGCGTCACAGCCCTCCTGTCCATGTGGATCAGTAACACGGCAACCACGGCCATGATGGTGCCCATCGTGGAGGCCATATTGCAGCAGATGGAAGCCACAAGCGCAGCCACCGAGGCCGGCCTGGAGCTGGTGGACAAGGGCAAGGCCAAGGAGCTGCCAGGGAGTCAAGTGATTTTTGAAGGCCCCACTCTGGGGCAGCAGGAAGACCAAGAGCGGAAGAGGTTGTGTAAGGCCATGACCCTGTGCATCTGCTACGCGGCCAGCATCGGGGGCACCGCCACCCTGACCGGGACGGGACCCAACGTGGTGCTCCTGGGCCAGATGAACGAGTTGTTTCCTGACAGCAAGGACCTCGTGAACTTTGCTTCCTGGTTTGCATTTGCCTTTCCCAACATGCTGGTGATGCTGCTGTTCGCCTGGCTGTGGCTCCAGTTTGTTTACATGAGATTCAATTTTAAAAAGTCCTGGGGCTGCGGGCTAGAGAGCAAGAAAAACGAGAAGGCTGCCCTCAAGGTGCTGCAGGAGGAGTACCGGAAGTTGGGGCCCTTGTCCTTCGCGGAGATCAACGTGCTGATCTGCTTCTTCCTGCTGGTCATCCTGTGGTTCTCCCGAGACCCCGGCTTCATGCCCGGCTGGCTGACTGTTGCCTGGGTGGAGGGTGAGACAAAGTATGTCTCCGATGCCACTGTGGCCATCTTTGTGGCCACCCTGCTATTCATTGTGCCTTCACAGAAGCCCAAGTTTAACTTCCGCAGCCAGACTGAGGAAGAAAGGAAAACTCCATTTTATCCCCCTCCCCTGCTGGATTGGAAGGTAACCCAGGAGAAAGTGCCCTGGGGCATCGTGCTGCTACTAGGGGGCGGATTTGCTCTGGCTAAAGGATCCGAGGCCTCGGGGCTGTCCGTGTGGATGGGGAAGCAGATGGAGCCCTTGCACGCAGTGCCCCCGGCAGCCATCACCTTGATCTTGTCCTTGCTCGTTGCCGTGTTCACTGAGTGCACAAGCAACGTGGCCACCACCACCTTGTTCCTGCCCATCTTTGCCTCCATGGTGAAAACAGGAGTCATAATGAACATAATTGGAGTCTTCTGTGTGTTTTTGGCTGTCAACACCTGGGGACGGGCCATATTTGACTTGGATCATTTCCCTGACTGGGCTAATGTGACACATATTGAGACTTAGGAAGAGCCACAAGACCACACACATAGCCCTTACCCTORF Start: ATG at 2ORF Stop: TAG at 1568SEQ ID NO:50522 aaMW at 58109.6 kDNOV14d,MASALSYVSKFKSFVILFVTPLLLLPLVILMPAKFVRCAYVIILMAIYWCTEVIPLAVCG57758-04 Protein SequenceTSLMPVLLFPLFQILDSRQVCVQYMKDTNMLFLGGLIVAVAVERWNLHKRIALRTLLWVGAKPARLMLGFMGVTALLSMWISNTATTAMMVPIVEAILQQMEATSAATEAGLELVDKGKAKELPGSQVIFEGPTLGQQEDQERKRLCKAMTLCICYAASIGGTATLTGTGPNVVLLGQMNELFPDSKDLVNFASWFAFAFPNMLVMLLFAWLWLQFVYMRFNFKKSWGCGLESKKNEKAALKVLQEEYRKLGPLSFAEINVLICFFLLVILWFSRDPGFMPGWLTVAWVEGETKYVSDATVAIFVATLLFIVPSQKPKFNFRSQTEEERKTPFYPPPLLDWKVTQEKVPWGIVLLLGGGFALAKGSEASGLSVWMGKQMEPLHAVPPAAITLILSLLVAVFTECTSNVATTTLFLPIFASMVKTGVIMNIIGVFCVFLAVNTWGRAIFDLDHFPDWANVTHIETSEQ ID NO:511781 BPNOV14e,GATGGCCTCGGCGCTGAGCTATGTCTCCAAGTTCAAGTCCTTCGTGATCTTGTTCGTCCG57758-05 DNA SequenceACCCCGCTCCTGCTGCTGCCACTCGTCATTCTGATGCCCGCCAAGTTTGTCAGGTGTGCCTACGTCATCATCCTCATGGCCATTTACTGGTGCACAGAAGTCATCCCTCTGGCTGTCACCTCTCTCATGCCTGTCTTGCTTTTCCCACTCTTCCAGATTCTGGACTCCAGGCAGGTGTGTGTCCAGTACATGAAGGACACCAACATGCTGTTCCTGGGCGGCCTCATCGTGGCCGTGGCTGTGGAGCGCTGGAACCTGCACAAGAGGATCGCCCTGCGCACGCTCCTCTGGGTGGGGGCCAAGCCTGCACGGCTGATGCTGGGCTTCATGGGCGTCACAGCCCTCCTGTCCATGTGGATCAGTAACACGGCAACCACGGCCATGATGGTGCCCATCGTGGAGGCCATATTGCAGCAGATGGAAGCCACAAGCGCAGCCACCGAGGCCGGCCTGGAGCTGGTGGACAAGGGCAAGGCCAAGGAGCTGCCAGGGAGTCAAGTGATTTTTGAAGGCCCCACTCTGGGGCAGCAGGAAGACCAAGAGCGGAAGAGGTTGTGTAAGGCCATGACCCTGTGCATCTGCTACGCGGCCAGCATCGGGGGCACCGCCACCCTGACCGGGACGGGACCCAACGTGGTGCTCCTGGGCCAGATGAACGAGTTGTTTCCTGACAGCAAGGACCTCGTGAACTTTGCTTCCTGGTTTGCATTTGCCTTTCCCAACATGCTGGTGATGCTGCTGTTCGCCTGGCTGTGGCTCCAGTTTGTTTACATGAGATTCAATTTTAAAAAGTCCTGGGGCTGCGGGCTAGAGAGCAAGAAAAACGAGAAGGCTGCCCTCAAGGTGCTGCAGGAGGAGTACCGGAAGTTGGGGCCCTTGTCCTTCGCGGAGATCAACGTGCTGATCTGCTTCTTCCTGCTGGTCATCCTGTGGTTCTCCCGAGACCCCGGCTTCATGCCCGGCTGGCTGACTGTTGCCTGGGTGGAGGGTGAGACAAAGTATGTCTCCGATGCCACTGTGGCCATCTTTGTGGCCACCCTGCTATTCATTGTGCCTTCACAGAAGCCCAAGTTTAACTTCCGCAGCCAGACTGAGGAAGAAAGGAAAACTCCATTTTATCCCCCTCCCCTGCTGGATTGGAAGGTAACCCAGGAGAAAGTGCCCTGGGGCATCGTGCTGCTACTAGGGGGCGGATTTGCTCTGGCTAAAGGATCCGAGGCCTCGGGGCTGTCCGTGTGGATGGGGAAGCAGATGGAGCCCTTGCACGCAGTGCCCCCGGCAGCCATCACCTTGATCTTGTCCTTGCTCGTTGCCGTGTTCACTGAGTGCACAAGCAACGTGGCCACCACCACCTTGTTCCTGCCCATCTTTGCCTCCATGAATCACGTCCCCAAGAGCTTCTGTGTTCTGTACGGTGATGTTGCAGTGCTGTCTTTCCGCAGTCTCGCTCCATCGGCCTCAATCCGCTGTACATCATGCTGCCCTGTACCCTGAGTGCCTCCTTTGCCTTCATGTTGCCTGTGGCCACCCCTCCAAATGCCATCGTGTTCACCTATGGGCACCTCAAGGTTGCTGACATGGTGAAAACAGGAGTCATAATGAACATAATTGGAGTCTTCTGTGTGTTTTTGGCTGTCAACACCTGGGGACGGGCCATATTTGACTTGGATCATTTCCCTGACTGGGCTAATGTGACACATATTGAGACTTAGGAAGAGCCACAORF Start: ATG at 2ORF Stop: TGA at 1550SEQ ID NO:52516 aaMW at 57173.5 kDNOV14e,MASALSYVSKFKSFVILFVTPLLLLPLVILMPAKFVRCAYVILMAIYWCTEVIPLAVCG57758-05 Protein SequenceTSLMPVLLFPLFQILDSRQVCVQYMKDTNMLFLGGLIVAVAVERWNLHKRIALRTLLWVGAKPARLMLGFMGVTALLSMWISNTATTAMMVPIVEAILQQMEATSAATEAGLELVDKGKAKELPGSQVIFEGPTLGQQEDQERKRLCKAMTLCICYAASIGGTATLTGTGPNVVLLGQMNELFPDSKDLVNFASWFAFAFPNMLVMLLFAWLWLQFVYMRFNFKKSWGCGLESKKNEKAALEVLQEEYRKLGPLSFAEINVLICFFLLVILWFSRDPGFMPGWLTVAWVEGETKYVSDATVAIFVATLLFIVPSQKPKFNFRSQTEEERKTPFYPPPLLDWKVTQEKVPWGIVLLLGGGFALAKGSEASGLSVWMGKQMEPLHAVPPAAITLILSLLVAVFTECTSNVATTTLFLPIFAS


[0396] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 14B.
73TABLE 14BComparison of NOV14a against NOV14b through NOV14e.ProteinNOV14a Residues/Identities/SimilaritiesSequenceMatch Residuesfor the Matched RegionNOV14b1 . . . 568519/616 (84%)1 . . . 616524/616 (84%)NOV14c1 . . . 568519/616 (84%)1 . . . 616524/616 (84%)NOV14d1 . . . 568483/570 (84%)1 . . . 522485/570 (84%)NOV14e1 . . . 480440/482 (91%)1 . . . 480443/482 (91%)


[0397] Further analysis of the NOV14a protein yielded the following properties shown in Table 14C.
74TABLE 14CProtein Sequence Properties NOV14aPSort0.6400 probability located in plasma membrane; 0.4600analysis:probability located in Golgi body; 0.3700 probability locatedin endoplasmic reticulum (membrane); 0.1000 probabilitylocated in endoplasmic reticulum (lumen)SignalPLikely cleavage site between residues 38 and 39analysis:


[0398] A search of the NOV14a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 14D.
75TABLE 14DGeneseq Results for NOV14aIdentities/NOV14aSimilaritiesProtein/Residues/for theGeneseqOrganism/LengthMatchMatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAB23625Human secreted10 . . . 566 256/623e−137protein SEQ ID NO:(41%)50—Homo sapiens,9 . . . 623386/623627 aa.(61%)[WO200049134-A1,Aug. 24, 2000]AAB36158Novel human10 . . . 566 256/623e−137transporter protein(41%)SEQ ID NO: 2—9 . . . 623386/623Homo sapiens,(61%)627 aa.[WO200065055-A2,Nov. 2, 2000]AAB42213Human ORFX10 . . . 566 256/623e−136ORF1977 poly-(41%)peptide sequence9 . . . 623386/623SEQ ID NO:(61%)3954—Homosapiens, 627 aa.[WO200058473-A2,Oct. 5, 2000]AAB36164Novel human10 . . . 566 252/623e−136transporter protein(40%)SEQ ID NO: 14—9 . . . 622382/623Homo sapiens,(60%)626 aa.[WO200065055-A2,Nov. 2, 2000]AAB36159Novel human10 . . . 566 256/623e−136transporter protein(41%)SEQ ID NO: 4—9 . . . 623385/623Homo sapiens,(61%)627 aa.[WO200065055-A2,Nov. 2, 2000]


[0399] In a BLAST search of public sequence databases, the NOV14a protein was found to have homology to the proteins shown in the BLASTP data in Table 14E.
76TABLE 14EPublic BLASTP Results for NOV14aNOV14aIdentities/ProteinResidues/SimilaritiesAccessionProtein/Matchfor theExpectNumberOrganism/LengthResiduesMatched PortionValueO57661INTESTINAL1 . . . 564336/619 (54%)0.0SODIUM/1 . . . 619444/619 (71%)LITHIUMDEPENDENT DI-CARBOXYLATETRANSPORTER(NA(+)/DI-CARBOXYLATECOTRANS-PORTER)—Xenopus laevis(African clawedfrog), 622 aa.Q9ES88NA/DICARB-1 . . . 561311/572 (54%)e−179OXYLATE CO-1 . . . 567421/572 (73%)TRANSPORTER(SOLUTECARRIERFAMILY 13(SODIUM-TRANSPORTER),MEMBER 2)—Mus musculus(Mouse), 586 aa.O35055SODIUM/DI-1 . . . 562311/572 (54%)e−179CARBOXYLATE1 . . . 568419/572 (72%)COTRANS-PORTER 1(NA(+)/DI-CARBOXYLATECOTRANS-PORTER 1)(KIDNEY DI-CARBOXYLATETRANSPORTER)(SDCT1)(ORGANIC ANIONTRANSPORTER 1)(OAT1)—Rattusnorvegicus (Rat),587 aa.Q13183Renal sodium/1 . . . 561318/581 (54%)e−179dicarboxylate1 . . . 572428/581 (72%)cotransporter(Na(+)/dicarboxylatecotransporter)—Homo sapiens(Human), 592 aa.Q28615Renal sodium/1 . . . 562300/586 (51%)e−172dicarboxylate1 . . . 576418/586 (71%)cotransporter(Na(+)/dicarboxylatecotransporter)—Oryctolaguscuniculus (Rabbit),593 aa.


[0400] PFam analysis predicts that the NOV14a protein contains the domains shown in the Table 14F.
77TABLE 14FDomain Analysis of NOV14aNOV14aIdentities/SimilaritiesExpectPfam DomainMatch Regionfor the Matched RegionValueNa_sulph_symp:6 . . . 554163/604 (27%)8.3e−140domain 1 of 1424/604 (70%)



Example 15

[0401] The NOV15 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 15A.
78TABLE 15ANOV15 Sequence AnalysisSEQ ID NO:531547 bpNOV15a,AACCCCCTTGACTGAAGCAATGGAGGGGGGTCCAGCTGTCTGCTGCCAGGATCCTCGGCG57732-01 DNA SequenceGCAGAGCTGGTAGAACGGGTGGCAGCCATCGATGTGACTCACTTGGAGGAGGCAGATGGTGGCCCAGAGCCTACTAGAAACGGTGTGGACCCCCCACCACGGGCCAGAGCTGCCTCTGTGATCCCTGGCAGTACTTCAAGACTGCTCCCAGCCCGGCCTAGCCTCTCAGCCAGGAAGCTTTCCCTACAGGAGCGGCCAGCAGGAAGCTATCTGGAGGCGCAGGCTGGGCCTTATGCCACGGGGCCTGCCAGCCACATCTCCCCCCGGGCCTGGCGGAGGCCCACCATCGAGTCCCACCACGTGGCCATCTCAGATGCAGAGGACTGCGTGCAGCTGAACCAGTACAAGCTGCAGAGTGAGATTGGCAAGGGTGCCTACGGTGTGGTGAGGCTGGCCTACAACGAAAGTGAAGACAGACACTATGCAATGAAAGTCCTTTCCAAAAAGAAGTTACTGAAGCAGTATGGCTTTCCACGTCGCCCTCCCCCGAGAGGGTCCCAGGCTGCCCAGGGAGGACCAGCCAAGCAGCTGCTGCCCCTGGAGCGGGTGTACCAGGAGATTGCCATCCTGAAGAAGCTGGACCACGTGAATGTGGTCAAACTGATCGAGGTACTGGATGACCCAGCTGAGGACAACCTCTATTTGCCCCGCATCCTTCTCCATAGGCCCGTCATGGAAGTGCCCTGTGACAAGCCCTTCTCGGAGGAGCAAGCTCGCCTCTACCTGCGGGACGTCATCCTGGGCCTCGAGTACGTGCACTGCCAGAAGATCGTCCACAGGGACATCAAGCCATCCAACCTGCTCCTGGGGGATGATGGGCACGTGAAGATCGCCGACTTTGGCGTCAGCAACCAGTTTGAGGGGAACGACGCTCAGCTGTCCAGCACGGCGGGAACCCCAGCATTCATGGCCCCCGAGGCCATTTCTGATTCCGGCCAGAGCTTCAGTGGGAAGTTGGATGTATGGGCCACTGGCGTCACGTTGTACTGCTTTGTCTATGGGAAGTGCCCATTCATCGACGATTTCATCCTGGCCCTCCACAGGAAGATCAAGAATGAGCCCGTGGTGTTTCCTGAGGAGCCAGAAATCAGCGAGGAGCTCAAGGACCTGATCCTGAAGATGTTAGACAAGAATCCCGAGACGAGAATTGGGGTGCCAGACATCAAGTTGCACCCTTGGGTGACCAAGAACGGGGAGGAGCCCCTTCCTTCGGAGGAGGAGCACTGCAGCGTGGTGGAGGTGACAGAGGAGGAGGTTAAGAACTCAGTCAGGCTCATCCCCAGCTGGACCACGGTGATCCTGGTGAAGTCCATGCTGAGGAAGCGTTCCTTTGGGAACCCGTTTGAGCCCCAAGCACGGAGGGAAGAGCGATCCATGTCTGCTCCAGGAAACCTACTGGTGAAAGAAGGGTTTGGTGAAGGGGGCAAGAGCCCAGAGCTCCCCGGCGTCCAGGAAGACGAGGCTGCATCCTGAGCCCCTGCATGCACCCORF Start: ATG at 20ORF Stop: TGA at 1529SEQ ID NO:54503 aaMW at 55606.7 kDNOV15a,MEGGPAVCCQDPRAELVERVAAIDVTHLEEADGGPEPTRNGVDPPPRARAASVIPGSTCG57732-01 Protein SequenceSRLLPARPSLSARKLSLQERPAGSYLEAQAGPYATGPASHISPRAWRRPTIESHHVAISDAEDCVQLNQYKLQSEIGKGAYGVVRLAYNESEDRHYAMKVLSKKKLLKQYGFPRRPPPRGSQAAQGGPAKQLLPLERVYQEIAILKKLDHVNVVKLIEVLDDPAEDNLYLPRILLERPVMEVPCDKPFSEEQARLYLRDVILGLEYVHCQKIVHRDIKPSNLLLGDDGHVKIADFGVSNQFEGNDAQLSSTAGTPAFMAPEAISDSGQSFSGKLDVWATGVTLYCFVYGKCPFIDDFILALHRKIKNEPVVFPEEPEISEELKDLILKMLDKNPETRIGVPDIKLHPWVTKNGEEPLPSEEEHCSVVEVTEEEVKNSVRLIPSWTTVILVKSMLRKRSFGNPFEPQARREERSMSAPGNLLVKEGFGEGGKSPELPGVQEDEAASSEQ ID NO:551611 bpNOV15b,GCGCCCAGGTTCCCAACAAGGCTACGCAGAAGAACCCCCTTGACTGAAGCAATGGAGGCG57732-02 DNA SequenceGGGGTCCAGCTGTCTGCTGCCAGGATCCTCGGGCAGAGCTGGTAGAACGGGTGGCAGCCATCGATGTGACTCACTTGGAGGAGGCAGATGGTGGCCCAGAGCCTACTAGAAACGGTGTGGACCCCCCACCACGGGCCAGAGCTGCCTCTGTGATCCCTGGCAGTACTTTAAGACTGCTCCCAGCCCGGCCTAGCCTCTCAGCCAGGAAGCTTTCCCTACAGGAGCGGCCAGCAGGAAGCTATCTGGAGGCGCAGGCTGGGCCTTATGCCACGGGGCCTGCCAGCCACATCTCCCCCCGGGCCTGGCGGAGGCCCACCATCGAGTCCCACCACGTGGCCATCTCAGATGCAGAGGACTGCGTGCAGCTGAACCAGTACAAGCTGCAGAGTGAGATTGGCAAGGGTGCCTACGGTGTGGTGAGGCTGGCCTACAACGAAAGTGAAGACAGACACTATGCAATGAAAGTCCTTTCCAAAAAGAAGTTACTGAAGCAGTATGGCTTTCCACGTCGCCCTCCCCCGAGAGGGTCCCAGGCTGCCCAGGGAGGACCAGCCAAGCAGCTGCTGCCCCTGGAGCGGGTGTACCAGGAGATTGCCATCCTGAAGAAGCTGGACCACGTGAATGTGGTCAAACTGATCGAGGTCCTGGATGACCCAGCTGAGGACAACCTCTATTTGGTGTTTGACCTCCTGAGAAAGGGGCCCGTCATGGAAGTGCCCTGTGACAAGTCCTTCTCGGAGGAGCAAGCTCGCCTCTACCTGCGGGACGTCATCCTGGGCCTCGAGTACTTGCACTGCCAGAAGATCSTCCACAGGGACATCAAGCCATCCAACCTGCTCCTGGGGGATGATGGGCACGTGAAGATCGCCGACTTTGGCGTCAGCAACCAGTTTGAGGGGAACGACGCTCAGCTGTCCAGCACGGCGGGAACCCCAGCATTCATGGCCCCCGAGGCCATTTCTGATTCCGGCCAGAGCTTCAGTGGGAAGGCCTTGGATGTATGGGCCACTGGCGTCACGCTGTACTGCTTTGTCTATGGGAAGTGCCCGTTCATCGACGATTTCATCCTGGCCCTCCACAGGAAGATCAAGAATGAGCCCGTGGTGTTTCCTGAGGGGCCAGAAATCAGCGAGGAGCTCAAGGACCTGATCCTGAAGATGATCCTGGTGAAGTCCATGCTGAGGAAGCGTTCCTTTGGGAACCCGTTTGAGCCCCAAGCACGGAGGGAAGAGCGATCCATGTCTGCTCCAGGAAACCTACTGGTGAAAGAAGGGTTTGGTGAAGGGGGCAAGAGCCCAGAGCTCCCCGGCGTCCAGGAAGACGAGGCTGCATCCTGAGCCCCTGCATGCACCCAGGGCCACCCGGCAGCACACTCATCCORF Start: ATG at 52ORF Stop: TGA at 1567SEQ ID NO:56505 aaMW at 55652.7 kDNOV15b,MEGGPAVDDQDPRAELVERVAAIDVTHLEEADGGPEPTRNGVDPPPRARAASVIPGSTCG57732-02 Protein SequenceSRLLPARPSLSARKLSLQERPAGSYLEAQAGPYATGPASHISPRAWRRPTIESHHVAISDAEDCVQLNQYKLQSEIGKGAYGVVRLAYNESEDRHYAMKVLSKKKLLKQYGFPRRPPPRGSQAAQGGPAEQLLPLERVYQEIAILKKLDHVNVVKLIEVLDDPAEDNLYLVFDLLRKGPVMEVPCDKSFSEEQARLYLRDVILGLEYLHCQKIVHRDIKPSNLLLGDDGHVKIADFGVSNQFEGNDAQLSSTAGTPAFMAPEAISDSGQSFSGKALDVWATGVTLYCFVYGKCPFIDDFILALHRKIKNEPVVFPEGPEISEELKDLILKMLDKNPETRIGVPDIKLHPWVTKNGEEPLPSEEEHCSVVEVTEEEVKNSVRLIPSWTTVILVKSMLRKRSFGNPPEPQARREERSMSAPGNLLVKEGFGEGGKSPELPGVQEDEAASSEQ ID NO:571725 bpNOV15c,GCGCCCAGGTTCCCAACAAGGCTACGCAGAAGAACCCCCTTGACTGAAGTAATGGAGGCG57732-03 DNA SequenceGGGGTCCAGCTGTCTGCTGCCAGGATCCTCGGGCAGAGCTGGTAGAACGGGTGGCAGCCATCGATGTGACTCACTTGGAGGAGGCAGATGGTGGCCCAGAGCCTACTAGAAACGGTGTGGACCCCCCACCACGGGCCAGAGCTGCCTCTGTGATCCCTGGCAGTACTTCAAGACTGCTCCCAGCCCGGCCTAGCCTCTCAGCCAGGAAGCTTTCCCTACAGGAGCGGCCAGCAGGAAGCTATCTGGAGGCGCAGGCTGGGCCTTATGCCACGGGGCCTGCCAGCCACATCTCCCCCCGGGCCTGGCGGAGGCCCACCATCGAGTCCCACCACGTGGCCATCTCAGATGCAGAGGACTGCGTGCAGCTGAACCAGTACAAGCTGCAGAGTGAGATTGGCAAGGGTGCCTACGGTGTGGTGAGGCTGGCCTACAACGAAAGTGAAGACAGACACTATGCAATGAAAGTCCTTTCCAAAAAGAAGTTACTGAAGCAGTATGGCTTTCCACGTCGCCCTCCCCCGAGAGGGTCCCAGGCTGCCCAGGGAGGACCAGCCAAGCAGCTGCTGCCCCTGGAGCGGGTGTACCAGGAGATTGCCATCCTGAAGAAGCTGGACCACGTGAATGTGGTCAAACTGATCGAGGTCCTGGATGACCCGGCTGAGGACAACCTCTATTTGGCCCTGCAGAACCAGGCCCAGAATATCCAGTTAGATTCAACAAATATCGCCAAGTCCCACTCCCTGCTTCCCTCTGAGCAGCAAGACAGTGGATCCACGTGGGCTGCGCGCTCAGTGTTTGACCTCCTGAGAAAGGGGCCCGTCATGGAAGTGCCCTGTGACAAGCCCTTCTCGGAGGAGCAAGCTCGCCTCTACCTGCGGGACGTCATCCTGGGCCTCGAGTACTTGCACTGCCAGAAGATCGTCCACAGGGACATCAAGCCATCCAACCTGCTCCTGGGGGATGATGGGCACGTGAAGATCGCCGACTTTGGCGTCAGCAACCAGTTTGAGGGGAACGACGCTCAGCTGTCCAGCACGGCGGGAACCCCAGCATTCATGGCCCCCGAGGCCATTTCTGATTCCGGCCAGAGCTTCAGTGGGAAGGCCTTGGATGTATGGGCCACTGGCGTCACGTTGTACTGCTTTGTCTATGGGAAGTGCCCGTTCATCGACGATTTCATCCTGGCCCTCCACAGGAAGACCAAGAATGAGCCCGTGGTGTTTCCTGAGGGGCCAGAAATCAGCGAGGAGCTCAAGGACCTGATCCTGAAGATGTTAGACAAGAATCCCGAGACGAGAATTGGGGTGCCAGACATCAAGTTGCACCCTTGGGTGACCAAGAACGGGGAGGAGCCCCTTCCTTCGGAGGAGGAGCACTGCAGCGTGGTGGAGGTGACAGAGGAGGAGGTTAAGAACTCAGTCAGGCTCATCCCCAGCTGGACCACGGTGATCCTGGTGAAGTCCATGCTGAGGAAGCGTTCCTTTGGGAACCCGTTTGAGCCCCAAGCACGGAGGGAAGAGCGATCCATGTCTGCTCCAGGAAACCTACTGGTGAAAGAAGGGTTTGGTGAAGGGGGCAAGAGCCCAGAGCTCCCCGGCGTCCAGGAAGACGAGGCTGCATCCTGAGCCCCTGCATGCACCCAGGGCCACCCGGCAGCACACTCATCCORF Start: ATG at 52ORF Stop: TGA at 1681SEQ ID NO:58543 aaMW at 59729.0 kDNOV15c,MEGGPAVCCQDPRAELVERVAAIDVTHLEEADGGPEPTRNGVDPPPRARAASVIPGSTCG57732-03 Protein SequenceSRLLPARPSLSARKLSLQERPAGSYLEAQAGPYATGPASHISPRAWRRPTIESHHVAISDAEDCVQLNQYKLQSEIGKGAYGVVRLAYNESEDRHYAMKVLSKKKLLKQYGFPRRPPPRGSQAAQGGPAKQLLPLERVYQEIAILKKLDHVNVVKLIEVLDDPAEDNLYLALQNQAQNIQLDSTNIAKSHSLLPSEQQDSGSTWAARSVFDLLRKGPVMEVPCDKPFSEEQARLYLRDVILGLEYLHCQKIVHRDIKPSNLLLGDDGHVKIADFGVSNQFEGNDAQLSSTAGTPAFMAPEAISDSGQSFSGKALDVWATGVTLYCFVYGKCPPIDDFILALHRKTKNEPVVFPEGPEISEELKDLILKMLDKNPETRIGVPDIKLHPWVTKNGEEPLPSEEEHCSYVEVTEEEVKNSVRLIPSWTTVILVKSMLRKRSFGNPFEPQARREERSMSAPGNLLVKEGFGEGGKSPELPGVQEDEAAS


[0402] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 15B.
79TABLE 15BComparison of NOV15a against NOV15b through NOV15c.ProteinNOV15a Residues/Identities/SimilaritiesSequenceMatch Residuesfor the Matched RegionNOV15b1 . . . 503495/505 (98%)1 . . . 505497/505 (98%)NOV15c1 . . . 503492/543 (90%)1 . . . 543495/543 (90%)


[0403] Further analysis of the NOV15a protein yielded the following properties shown in Table 15C.
80TABLE 15CProtein Sequence Properties NOV15aPSort0.7600 probability located in nucleus; 0.3000 probability located inanalysis:microbody (peroxisome); 0.1000 probability located in mitochondrialmatrix space; 0.1000 probability located in lysosome (lumen)SignalPNo Known Signal Sequence Predictedanalysis:


[0404] A search of the NOV15a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 15D.
81TABLE 15DGeneseq Results for NOV15aIdentities/NOV15aSimilaritiesProtein/Residues/for theGeneseqOrganism/LengthMatchMatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAU03510Human protein 1 . . . 503496/5130.0kinase #10—Homo(96%)sapiens, 513 aa. 1 . . . 513498/513[WO200138503-A2,(96%)May 31, 2001]AAE04361Human kinase 1 . . . 503496/5130.0(PKIN)-2—Homo(96%)sapiens, 513 aa. 1 . . . 513498/513[WO200146397-A2,(96%)Jun. 28, 2001]AAY44239Human cell 64 . . . 500289/450e−165signalling protein-(64%)2—Homo sapiens, 90 . . . 538367/450540 aa.(81%)[WO9958558-A2,Nov. 18, 1999]AAM40450Human polypeptide 64 . . . 482283/432e−162SEQ ID NO 5381—(65%)Homo sapiens,128 . . . 558356/432680 aa.(81%)[WO200153312-A1,Jul. 26, 2001]AAM40449Human polypeptide 64 . . . 482283/432e−162SEQ ID NO 5380—(65%)Homo sapiens,128 . . . 558356/432680 aa.(81%)[WO200153312-A1,Jul. 26, 2001]


[0405] In a BLAST search of public sequence databases, the NOV15a protein was found to have homology to the proteins shown in the BLASTP data in Table 15E.
82TABLE 15EPublic BLASTP Results for NOV15aNOV15aIdentities/ProteinResidues/Similarities forAccessionProtein/Matchthe MatchedExpectNumberOrganism/LengthResiduesPortionValueQ9BQH3HYPOTHETICAL1 . . . 503497/505 (98%)0.055.7 KDA1 . . . 505499/505 (98%)PROTEIN—Homosapiens (Human),505 aa.P97756CA2+/1 . . . 503465/505 (92%)0.0CALMODULIN-1 . . . 505478/505 (94%)DEPENDENTPROTEIN KINASEIV KINASEISOFORM—Rattusnorvegicus (Rat),505 aa.AAH17529SIMILAR TO1 . . . 503464/505 (91%)0.0CALCIUM/1 . . . 505478/505 (93%)CALMODULIN-DEPENDENTPROTEIN KINASEKINASE 1,ALPHA—Musmusculus (Mouse),505 aa.Q64572CA2+/1 . . . 503463/505 (91%)0.0CALMODULIN-1 . . . 505476/505 (93%)DEPENDENTPROTEIN KINASEKINASE (EC2.7.1.37)—Rattusnorvegicus (Rat),505 aa.Q9R054CALCIUM/1 . . . 503454/505 (89%)0.0CALMODULIN1 . . . 505471/505 (92%)DEPENDENTPROTEIN KINASEKINASE ALPHA—Mus musculus(Mouse), 505 aa.


[0406] PFam analysis predicts that the NOV15a protein contains the domains shown in the Table 15F.
83TABLE 15FDomain Analysis of NOV15aNOV15aIdentities/SimilaritiesExpectPfam DomainMatch Regionfor the Matched RegionValuePkinase: domain128 . . . 228 28/101 (28%)8.4e−161 of 2 81/101 (80%)Pkinase: domain245 . . . 407 70/201 (35%)1.7e−521 of 2129/201 (64%)



Example 16

[0407] The NOV16 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 16A.
84TABLE 16ANOV16 Sequence AnalysisSEQ ID NO:59688 bpNOV16aGACGCGGACCCGCCATGGCGCGGAAGAAGGTGCGTCCGCGGCTGATCGCGGAGCTGGCCG57709-01 DNA SequenceCCGCCGCGTGCGCGCCCTGCGGGAGCAACTGAACAGGCCGCGCGACTCCCAGCTCTACGCGGTGGACTACGAGACCTTGACGCGGCCGTTCTCTGGACGCCGGCTGCCGGTCCGGGCCTGGGCCGACGTGCGCCGCGAGAGCCGCCTCTTGCAGCTGCTCGGCCGCCTCCCGCTCTTCGGCCTGGGCCGCCTGGTCACGCGCAAGTCCTGGCTGTGGCAGCACGACGAGCCGTGCTACTGGCGCCTCACGCGGGTGCGGCCCGACTACACGGCGCAGAACTTGGACCACGGGAAGGCCTGGGGCATCCTGACCTTCAAAGGTAAGGCTCGGGAGAGCGCGCGGGAGATCGAACACGTCATGTACCATGACTGGCGGCTGGTGCCCAAGCACGAGGAGGAGGCCTTCACCGCGTTCACGCCGGCGCCGGAAGACAGCCTGGCCTCCGTGCCGTACCCGCCTCTCCTCCGGGCCATGATTATCGCAGAACGACAGAAAAATGGAGACACAAGCACCGAGGAGCCCATGCTGAATGTGCAGAGGATACGCATGGAACCCTGGGATTACCCTGCAAAACAGGAAGACAAAGGAAGGGCCAAGGGCACCCCCGTCTAGAATGCCAGAACCAGCGGORF Start: ATG at 15ORF Stop: TAG at 669SEQ ID NO:60218 aaMW at 25647.2 kDNOV16a,MARKKVRPRLIAELARRVRALREQLNRPRDSQLYAVDYETLTRPFSGRRLPVRAWADVCG57709-01 Protein SequenceRRESRLLQLLGRLPLFGLGRLVTRKSWLWQHDEPCYWRLTRVRPDYTAQNLDHGKAWGILTFKGKARESAREIEHVMYHDWRLVPKHEEEAFTAFTPAPEDSLASVPYPPLLRAMIIAEROKNGDTSTEEPMLNVORIRMEPWDYPAKOEDKGRAKGTPV


[0408] Further analysis of the NOV16a protein yielded the following properties shown in Table 16B.
85TABLE 16BProtein Sequence Properties NOV16aPSort0.9081 probability located in mitochondrial matrix space;analysis:0.6000 probability located in mitochondrial inner membrane;0.6000 probability located in mitochondrial intermembranespace; 0.6000 probability located in mitochondrial outermembraneSignalPNo Known Signal Sequence Predictedanalysis:


[0409] A search of the NOV16a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 16C.
86TABLE 16CGeneseq Results for NOV16aNOV16aIdentities/Protein/Residues/Similarities forGeneseqOrganism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAG81356Human AFP 1 . . . 218212/218 e−125protein sequence (97%)SEQ ID NO: 1 . . . 218212/218230—Homo (97%)sapiens, 18 aa.[WO200129221-A2, Apr. 26,2001]AAU30525Novel human135 . . . 21884/843e−45 secreted protein(100%)[WO200179449- 1 . . . 8484/84A2, Oct. 25,(100%)2001]AAU30526Novel human187 . . . 21731/314e−12 secreted protein(100%)#1017—Homo12 . . . 4231/31sapiens, 62 aa.(100%)[WO200179449-A2, Oct. 25,2001]


[0410] In a BLAST search of public sequence databases, the NOV16a protein was found to have homology to the proteins shown in the BLASTP data in Table 16D.
87TABLE 16DPublic BLASTP Results for NOV16aNOV16aIdentities/ProteinResidues/Similarities forAccessionProtein/Matchthe MatchedExpectNumberOrganism/LengthResiduesPortionValueQ9BV17HYPOTHETICAL1 . . . 218214/218 (98%)e−12525.7 KDA1 . . . 218214/218 (98%)PROTEIN—Homosapiens (Human),218 aa.P82930MITO-1 . . . 218213/218 (97%)e−124CHONDRIAL 28S1 . . . 218213/218 (97%)RIBOSOMALPROTEIN S34(MRP-S34)—Homosapiens (Human),218 aa.CAC38606SEQUENCE 2291 . . . 218212/218 (97%)e−124FROM PATENT1 . . . 218212/218 (97%)WO0129221—Homo sapiens(Human), 218 aa.Q9JIK9TCE21 . . . 218194/218 (88%)e−114(0610007F04RIK1 . . . 218205/218 (93%)PROTEIN)—Mus musculus(Mouse), 218 aa.Q9D9570610007F04R1K1 . . . 218193/218 (88%)e−114PROTEN—1 . . . 218205/218 (93%)Mus musculus(Mouse), 218 aa.


[0411] PFam analysis predicts that the NOV16a protein contains the domains shown in the Table 16E.
88TABLE 16EDomain Analysis of NOV16aNOV16aIdentities/SimilaritiesExpectPfam DomainMatch Regionfor the Matched RegionValueNo Significant Matches Found



Example 17

[0412] The NOV17 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 17A.
89TABLE 17ANOV17 Sequence AnalysisSEQ ID NO:61894 bpNOV17a,CTCCGTGACCATGAAGGTCAAGGTCATCCCCGTGCTCGAGGACAACTACATGTACCTGCG57700-01 DNA SequenceGTCATCGAGGAGCTCACGCGCGAGGCGGTGGCCGTGGACGTGGCTGTGCCCAAGAGGCTGCTGGAGATCGTGGGCCGGGAGGGGGTGTCTCTGACCGCTGTGCTGACCACCCACCATCACTGGGACCACGCGCGGGGAAACCCGGAGCTGGCGCGGCTTCGTCCCGGGCTGGCGGTGCTGGGCGCGGACGAGCGCATCTTCTCGCTGACGCGCAGGCTGGCGCACGGCGAGGAGCTGCAGTTCGGGGCCATCCACGTGCGTTGCCTCCTGACGCCCGGCCACACCGCCCGCCACATGAGCTACTTCCTGTGGGAGGACGATTGCCCGGACCCACCCGCCCTGTTCTCGGGTGGCGACGCGCTGTCGGTGGCCGGCTGCGGCTCGTGCCTGGAGGGCAGCGCCCAGCAGATGTACCAGAGCCTGGCCGAGCTGGGTACCCTGCCCCCCGAGACGAAGGTGTTCTGCGGCCACGAGCACACGCTTAGCAACCTGGAGTTTGCCCAGAAAGTGGAGCCCTGCAACGACCACGTGAGAGCCAAGCTGTCCTGGGCTCAGAAGAGGGATGAGGATGACGTGCCCACTGTGCCGTCGACTCTGGGCGAGGAGCGCCTCTACAACCCCTTCCTGCGGGTGGCGGAGGAGCCGGTGCGCAAGTTCACGGGCAAGGCGGTCCCCGCCGACGTCCTGGAGGCGCTATGCAAGGAGCGGGCGCGCTTCGAACAGGCGGGCGAGCCGCGGCAGCCACAGGCGCGGGCCCTCCTTGCGCTGCAGTGGGGGCTCCTGAGTGCAGCCCCACACGACTGAGCCACCCAGACCCTCACAGGGCTGGGGCCTGCORF Start: ATG at 11ORF Stop: TGA at 860SEQ ID NO:62283 aaMW at 31262.3 kDNOV17a,MKVKVIPVLEDNYMYLVIEELTREAVAVDVAVPKRLLEIVGREGVSLTAVLTTHHHWDCG57700-01 Protein SequenceHARGNPELARLRPGLAVLGADERIFSLTRRLAHGEELQFGAIHVRCLLTPGHTAGHMSYFLWEDDCPDPPALFSGGDALSVAGCGSCLEGSAQQMYQSLAELGTLPPETKVFCGHEHTLSNLEFAQKVEPCNDHVRAKLSWAQKRDEDDVPTVPSTLGEERLYNPFLRVAEEPVRKFTGKAVPADVLEALCKERARFEQAGEPRQPQARALLALQWGLLSAAPHDSEQ ID NO:63888 bpNOV17b,CTCCGTGACCATGAAGGTCAAGGTCATCCCCGTGCTCGAGGACAACTACATGTACCTGCG57700-02 DNA SequenceGTCATCGAGGAGCTCACGCGCGAGGCGGTGGCCGTGGACGTGGCTGTGCCCAAGAGGCTGCTGGAGATCGTGGGCCGGGAGGGGGTGTCTCTGACCGCTGTGCTGACCACCCACCATCACTGGGACCACGCGCGGGGAAACCCGGAGCTGGCGCGGCTTCGTCCCGGGCTGGCGGTGCTGGGCGCGGACGAGCGCATCTTCTCGCTGACGCGCAGGCTGGCGCACGGCGAGGAGCTGCAGTTCGGGGCCATCCACGTGCGTTGCCTCCTGACGCCCGGCCACACCGCCGGCCACATGAGCTACTTCCTGTGGGAGGACGATTGCCCGGACCCACCCGCCCTGTTCTCGGGCGACGCGCTGTCGGTGGCCGGCTGCGGCTCGTGCCTGGAGGGCAGCGCCCAGCAGATGTACCAGAGCCTGGCCGAGCTGGGTACCCTGCCCCCCGAGACGAAGGTGTTCTGCGGCCACGAGCACACACTTAGCAACCTGGAGTTTGCCCAGAAAGTGGAGCCCTGCAACGACCACGTGAGAGCCAAGCTGTCCTGGGCTAAGAAGAGGGATGAGGATGACGTGCCCACTGTGCCGTCGACTCTGGGCGAGGAGCGCCTCTACAACCCCTTCCTGCGGGTGGCAGAGGAGCCGGTGCGCAAGTTCACGGGCAAGGCGGTCCCCGCCGACGTCCTGGAGGCGCTATGCAAGGAGCGGGCGCGCTTCGAACAGGCGGGCGAGCCGCGGCAGCCACAGGCGCGGGCCCTCCTTGCGCTGCAGTGGGGGCTCCTGAGTGCAGCCCCACACGACTGAGCCACCCAGACCCTCACAGGGCTGGGCCTORF Start: ATG at 11ORF Stop: TGA at 857SEQ ID NO:64282 aaMW at 31205.3 kDNOV17b,MKVKVIPVLEDNYMYLVIEELTREAVAVDVAVPKRLLEIVGREGVSLTAVLTTHHHWDCG57700-02 Protein SequenceHARGNPELARLRPGLAVLGADERIFSLTRRLAHGEELQFGAIHVRCLLTPGHTAGHMSYFLWEDDCPDPPALFSGDALSVAGCGSCLEGSAQQMYQSLAELGTLPPETKVFCGHEHTLSNLEFAQKVEPCNDHVRAKLSWAKKRDEDDVPTVPSTLGEERLYNPFLRVAEEPVRKFTGKAVPADVLEALCKERARFEQAGEPRQPQARALLALQWGLLSAAPHDSEQ ID NO:65882 bpNOV17c,ACCATGAAGGTCAAGGTCATCCCCGTGCTCGAGGACAACTACATGTACCTGGTCATCGCG57700-03 DNA SequenceAGGAGCTCACGCGCGAGGCGGTGGCCGTGGACGTGGCTGTGCCCAAGAGGCTGCTGGAGATCGTGGGCCGGGAGGGGGTGTCTCTGACCGCTGTGCTGACCACCCACCATCACTGGGACCACGCGCGGGGAAACCCGGAGCTGGCGCGGCTTCGTCCCGGGCTGGCGGTGCTGGGCGCGGACGAGCGCATCTTCTCGCTGACGCGCAGGCTGGCGCACGGCGAGGAGCTGCGGTTCGGGGCCATCCACGTGCGTTGCCTCCTGACGCCCGGCCACACCGCCGGCCACATGAGCTACTTCCTGTGGGAGGACGATTGCCCGGACCCACCCGCCCTGTTCTCGGGCGACGCGCTGTCGGTGGCCGGCTGCGGCTGGTCCGTGGAGGGCAGCCCCCAGGACATCTACCAGAGCCTGGCCGAGCTGGGTACCCTGCCCCCCGAGACGAAGGTGTTCTGCGGCCACGAGCACACGCTTAGCAACCTGGAGTTTGCCCAGAAAGTGGAGCCCTGCAACGACCACGTGAGAGCCAAGCTGTCCTGGGCTAAGAAGAGGGATGAGGATGACGTGCCCACTGTGCCGTCGACTCTGGGCGAGGAGCGCCTCTACAACCCCTTCCTGCGGGTGGCAGAGGAGCCGGTGCGCAAGTTCACGGGCAAGGCGGTCCCCGCCGACGTCCTGGAGGCGCTATGCAAGGAGCGGGCGCGCTCCGAACAGGCGGGCGAGCCGCGGCAGCCACAGGCGCGGGCCCTCCTTGCGCTGCAGTGGGGGCTCCTGAGTGCAGCCCCACACGACTGAGCCACCCAGACCCTCACAGGGCTGGGGCCTORF Start: ATG at 4ORF Stop: TGA at 850SEQ ID NO:66282 aaMW at 31173.2 kDNOV17c,MKVKVIPVLEDNYMYLVIEELTREAVAVDVAVPKRLLEIVGREGVSLTAVLTTHHHWDCG57700-03 Protein SequenceHARGNPELARLRPGLAVLGADERIFSLTRRLAHGEELRFGAIHVRCLLTPGHTAGHMSYFLWEDDCPDPPALFSGDALSVAGCGSCLEGSAQQMYQSLAELGTLPPETKVFCGHEHTLSNLEFAQKVEPCNDHVRAKLSWAKKRDEDDVPTVPSTLGEERLYNPFLRVAEEPVRKFTGKAVPADVLEALCKERARSEQAGEPRQPQARALLALQWGLLSAAPHDSEQ ID NO:67855 bpNOV17d,ACCATGAAGGTCAAGGTCATCCCCGTGCTCGAGGACAACTACATGTACCTGGTCATCGCG57700-04 DNA SequenceAGGAGCTCACGCGCGAGGCGGTGGCCGTGGACGTGGCTGTGCCCAAGAGGCTGCTGGAGATCGTGGGCCGGGAGGGGGTGTCTCTGACCGCTGTGCTGACCACCCACTATCACTGGGACCACGCGCGGGGAAACCCGGAGCTGGCGCGGCTTCGTCCCGGGCTGGCGGTGCTGGGCGCGGACGAGCGCATCTTCTCGCTGACGCGCAGGCTGGCGCACGGCGAGGAGCTGCGGTTCGGGGCCATCCACGTGCGTTGCCTCCTGACGCCCGGCCACACCGCCGGCCACATGAGCTACTTCCTGTGGGAGGACGATTGCCCGGACCCACCCGCCCTGTTCTCGGGCGACGCGCTGTCGGTGGCCGGCTGCGGCTCGTGCCTGGAGGGCAGCGCCCAGCAGATGTACCAGAGCCTGGCCGAGCTGGGTACCCTGCCCCCCGAGACGAAGGTGTTCTGCGGCCACGAGCACACGCTTAGCAACCTGGAGTTTGCCCAGAAAGTGGAGCCCTGCAACGACCACAAGAGGGATGAGGATGACGTGCCCACTGTGCCGTCGACTCTGGGCGAGGAGCGCCTCTACAACCCCTTCCTGCGGGTGGCAGAGGAGCCGGTGCGCAAGTTCACGGGCAAGGCGGTCCCCGCCGACGTCCTGGAGGCGCTATGCAAGGAGCGGGCGCGCTTCGAACAGGCGGGCGAGCCGCGGCAGCCACAGGCGCGGGCCCTCCTTGCGCTGCAGTGGGGGCTCCTGAGTGCAGCCCCACACGACTGAGCCACCCAGACCCTCACAGGGCTGGGGCCTORF Start: ATG at 4ORF Stop: TGA at 823SEQ ID NO:68273 aaMW at 30219.1 kDNOV17d,MKVKVIPVLEDNYMYLVIEELTREAVAVDVAVPKRLLEIVGREGVSLTAVLTTHYHWDCG57700-04 Protein SequenceHARGNPELARLRPGLAVLGADERIFSLTRRLAHGEELRFGAIHVRCLLTPGHTAGHMSYFLWEDDCPDPPALFSGDALSVAGCGSCLEGSAQQMYQSLAELGTLPPETKVFCGHEHTLSNLEFAQKVEPCNDHKRDEDDVPTVPSTLGEERLYNPFLRVAEEPVRKFTGKAVPADVLEALCKERARFEQAGEPRQPQARALLALQWGLLSAAPHD


[0413] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 17B.
90TABLE 17BComparison of NOV17a against NOV17b through NOV17d.ProteinNOV17a Residues/Identities/SimilaritiesSequenceMatch Residuesfor the Matched RegionNOV17b1 . . . 283281/283 (99%)1 . . . 282282/283 (99%)NOV17c1 . . . 283279/283 (98%)1 . . . 282281/283 (98%)NOV17d1 . . . 283271/283 (95%)1 . . . 273273/283 (95%)


[0414] Further analysis of the NOV17a protein yielded the following properties shown in Table 17C.
91TABLE 17CProtein Sequence Properties NOV17aPSort0.4500 probability located in cytoplasm; 0.3000 probabilityanalysis:located in microbody (peroxisome); 0.1682 probability locatedin lysosome (lumen); 0.1000 probability located inmitochondrial matrix spaceSignalPNo Known Signal Sequence Predictedanalysis:


[0415] A search of the NOV17a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 17D.
92TABLE 17DGeneseq Results for NOV17aNOV17aIdentities/Protein/Residues/Similarities forGeneseqOrganism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAW80783Human bisphos- 1 . . . 256128/257 (49%)6e−72phonate binding 1 . . . 256184/257 (70%)protein, DP1(hDP1)—Homosapiens, 260 aa.[WO9836064-A1,Aug. 20, 1998]AAG10987Arabidopsis 1 . . . 245107/248 (43%)5e−53thaliana protein 1 . . . 246160/248 (64%)fragment SEQ IDNO: 9531—Arabidopsisthaliana, 258 aa.[EP1033405-A2,Sep. 6, 2000]AAG10986Arabidopsis 1 . . . 245107/248 (43%)5e−53thaliana protein 11 . . . 256160/248 (64%)fragment SEQ IDNO: 9530—Arabidopsisthaliana, 268 aa.[EP1033405-A2,Sep. 6, 2000]AAM78721Human protein 1 . . . 226100/227 (44%)6e−45SEQ ID NO119 . . . 344135/227 (59%)1383—Homosapiens, 385 aa.[WO200157190-A2, Aug. 9,2001]AAY71110Human Hydrolase 1 . . . 226100/227 (44%)6e−45protein-8 95 . . . 320135/227 (59%)(HYDRL-8)—Homo sapiens,361 aa.[WO200028045-A2, May 18,2000]


[0416] In a BLAST search of public sequence databases, the NOV17a protein was found to have homology to the proteins shown in the BLASTP data in Table 17E.
93TABLE 17EPublic BLASTP Results for NOV17aNOV17aIdentities/ProteinResidues/Similarities forAccessionProtein/Matchthe MatchedExpectNumberOrganism/LengthResiduesPortionValueQ9BT45SIMILAR TO RIKEN1 . . . 283280/283 (98%) e−163CDNA 1500017E181 . . . 282282/283 (98%)GENE—Homo sapiens(Human), 282 aa.Q9DB321500017E18R1K1 . . . 278231/279 (82%) e−133PROTEIN—Mus1 . . . 278251/279 (89%)musculus (Mouse),283 aa.Q96S11SIMILAR TO1 . . . 128217/228 (95%) e−123HAGH—Homo1 . . . 218218/228 (95%)sapiens (Human),218 aa.Q96NR5CDNA FLJ302791 . . . 133132/133 (99%)3e−73 FIS, CLONE1 . . . 133133/133 (99%)BRACE2002772,MODERATELYSIMILAR TOHYDROXYACYL-GLUTATHIONEHYDROLASE(BC 3.1.2.6)—Homosapiens (Human),202 aa.O35952Hydroxyacyl-1 . . . 256128/257 (49%)1e−71 glutathione hydrolase1 . . . 256184/257 (70%)(EC 3.1.2.6)(Glyoxalase II) (GlxII) (Round spermatidprotein RSP29)—Rattus norvegicus(Rat), 260 aa.


[0417] PFam analysis predicts that the NOV17a protein contains the domains shown in the Table 17F.
94TABLE 17FDomain Analysis of NOV17aNOV17aIdentities/SimilaritiesExpectPfam DomainMatch Regionfor the Matched RegionValuelactamase_B:7 . . . 173 55/221 (25%)5.8e−32domain 1 of 1129/221 (58%)



Example 18

[0418] The NOV18 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 18A.
95TABLE 18ANOV18 Sequence AnalysisSEQ ID NO:692109 bpNOV18a,GGGTCCGGCGGGCATCGGCAAGACCATGGCGGCCAAAAATATCCTGTACGACTGGGCGCG58553-01 DNA SequenceGCGGGCAAGCTGTACCAGGGCCAGGTGGACTTCGCCTTCTTCATGCCCTGCGGCGAGCTGCTGGAGAGGCCGGGCACGCGCAGCCTGGCTGACCTGATCCTGGACCAGTGCCCCGACCGCGGCGCGCCGGTGCCGCAGATGCTGGCCCAGCCGCAGCGGCTGCTCTTCATCCTGGACGGCGCGGACGAGCTGCCGGCGCTGGGGGGCCCCGAGGCCGCGCCCTGCACAGACCCCTTCGAGGCGGCGAGCGGCGCGCGGGTGCTAGGCGGGCTGCTGAGTAAGGCGCTGCTGCCCACGGCCCTCCTGCTGGTGACCACGCGCGCCGCCGCCCCCGGGAGGCTGCAGGGCCGCCTGTGTTCCCCGCAGTGCGCCGAGGTGCGCGGCTTCTCCGACAAGGACAAGAAGAAGTATTTCTACAAGTTCTTCCGGGATGAGAGGAGGGCCGAGCGCGCCTACCGCTTCGTGAAGGAGAACGAGACGCTGTTCGCGCTGTGCTTCGTGCCCTTCGTGTGCTGGATCGTGTGCACCGTGCTGCGCCAGCAGCTGGAGCTCGGTCGGGACCTGTCGCGCACGTCCAAGACCACCACGTCAGTGTACCTGCTTTTCATCACCAGCGTTCTGAGCTCGGCTCCGGTAGCCGACGGGCCCCGGTTGCAGGGCGACCTGCGCAATCTGTGCCGCCTGGCCCGCGAGGGCGTCCTCGGACGCAGGGCGCAGTTTGCCGAGAAGGAACTGGAGCAACTGGAGCTTCGTGGCTCCAAAGTGCAGACGCTGTTTCTCAGCAAAAAGGAGCTGCCGGGCGTGCTGGAGACAGAGGTCACCTACCAGTTCATCGACCAGAGCTTCCAGGAGTCCTTCGCGGCACTGTCCTACCTGCTGGAGGACGGCGGGGTGCCCAGGACCGCGGCTGGCGGCGTTGGGACACTCCTGCGTGGGGACGCCCAGCCGCACAGCCACTTGGTGCTCACCACGCGCTTCCTCTTCGGACTGCTGAGCGCGGAGCGGATGCGCGACATCGAGCGCCACTTCGGCTGCATGGTTTCAGAGCGTGTGAAGCAGGAGGCCCTGCGGTGGGTGCAGGGACAGGGACAGGGCTGCCCCGGAGTGGCACCAGAGGTGACCGAGGGGGCCAAAGGGCTCGAGGACACCGAAGAGCCAGAGGAGGAGGAGGAGGGAGAGGAGCCCAACTACCCACTGGAGTTGCTGTACTGCCTGTACGAGACGCAGGAGGACGCGTTTGTGCGCCAAGCCCTGGGCCGGTTCCCGGAGCTGGCGCTGCAGCGAGTGCGCTTCTGCCGCATGGACGTGGCTGTTCTGAGCTACTGCGTGAGGTGCTGCCCTGCTGCACAGGCACTGCGGCTGATCAGCTGCAGATTGGTTGCTGCGCAGGAGAAGAAGAAGAAGAGCCTGGGGAAGCGGCTCCAGGCCAGCCTGGGCACCACAAAACAACTGCCAGCCTCCCTTCTTCATCCACTCTTTCAGGCAATGACTGACCCACTGTGCCATCTGAGCAGCCTCACGCTGTCCCACTGCAAACTCCCTGACGCGGTCTGCCGAGACCTTTCTGAGGCCCTGAGGGCAGCCCCCGCACTGACGGAGCTGGGCCTCCTCCACAACAGGCTCAGTGAGGCAGGACTGCGTATGCTGAGTGAGGGCCTAGCCTGGCCGCAGTGCAGGGTGCAGACGGTCAGGGTACAGCTGCCTGACCCCCAGCGAGGGCTCCAGTACCTGGTGGGTATGCTTCGGCAGAGCCCTGCCCTGACCACCCTGGATCTCAGCGGCTGCCAACTGCCCGCCCCCATGGTGACCTACCTGTGTGCAGTCCTGCAGCACCAGGGATGCGGCCTGCAGACCCTCAGTCTGGCCTCTGTGGAGCTGAGCGAGCAGTCACTACAGGAGCTTCAGGCTGTGAAGAGAGCAAAGCCGGATCTGGTCATCACACACCCAGCGCTGGACGGCCACCCACAACCTCCCAAGGAACTCATCTCGACCTTCTGAGGCTCTGGTGGCCAGAGCAGGGTGGAAGACCCTAGTCAAAGTCCCTGTGGAGAORF Start: ATG at 26ORF Stop: TGA at 2054SEQ ID NO:70676 aaMW at 74650.3 kDNOV18a,MAAKNILYDWAAGKLYQGQVDFAFFMPCGELLERPGTRSLADLILDQCPDRGAPVPQMCG58553-01 Protein SequenceLAQPQRLLFILDGADELPALGGPEAAPCTDPFEAASGARVLGGLLSKALLPTALLLVTTRAAAPGRLQGRLCSPQCAEVRGFSDKDKKKYFYKFFRDERRAERAYRFVKENETLFALCFVPFVCWIVCTVLRQQLELGRDLSRTSKTTTSVYLLFITSVLSSAPVADGPRLQGDLRNLCRLAREGVLGRRAQFAEKELEQLELRGSKVQTLFLSKKELPGVLETEVTYQFIDQSFQESFAALSYLLEDGGVPRTAAGGVGTLLRGDAQPHSHLVLTTRFLFGLLSAERMRDIERHFGCMVSERVKQEALRWVQGQGQGCPGVAPEVTEGAKGLEDTEEPEEEEEGEEPNYPLELLYCLYETQEDAFVRQALGRFPELALQRVRFCRMDVAVLSYCVRCCPAAQALRLISCRLVAAQEKKKKSLGKRLQASLGTTKQLPASLLHPLFQAMTDPLCHLSSLTLSHCKLPDAVCRDLSEALRAAPALTELGLLHNRLSEAGLRMLSEGLAWPQCRVQTVRVQLPDPQRGLQYLVGMLRQSPALTTLDLSGCQLPAPMVTYLCAVLQHQGCGLQTLSLASVELSEQSLQELQAVKRAKPDLVITHPALDGHPQPPKELISTF


[0419] Further analysis of the NOV18a protein yielded the following properties shown in Table 18B.
96TABLE 18BProtein Sequence Properties NOV18aPsort0.7400 probability located in nucleus; 0.6000 probabilityanalysis:located in endoplasmic reticulum (membrane); 0.3000probability located in microbody (peroxisome); 0.1000probability located in mitochondrial inner membraneSignalPNo Known Signal Sequence Predictedanalysis:


[0420] A search of the NOV18a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 18C.
97TABLE 18CGeneseq Results for NOV18aNOV18aIdentities/Protein/Residues/Similarities forGeneseqOrganism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAE04546Human G-protein 1 . . . 676671/682 (98%)0.0coupled receptor-210 . . . 891671/682 (98%)2 (GCREC-2)protein—Homosapiens, 891 aa.[WO200142288-A2, Jun. 14,2001]AAU00023Human activated 1 . . . 633605/695 (87%)0.0T-lymphocyte210 . . . 904610/695 (87%)associatedsequence 2,ATLAS-2—Homo sapiens,1851 aa.[WO200114564-A2, Mar. 1, 2001]ABB11735Human vaso- 1 . . . 490485/490 (98%)0.0pressin receptor106 . . . 595485/490 (98%)homologue, SEQID NO:2105—Homo sapiens,597 aa.[WO200157188-A2, Aug. 9,2001]AAR33389AII/AVPv2193 . . . 670322/481 (66%)e−174receptor— 1 . . . 480371/481 (76%)Synthetic, 481 aa.[WO9305073-A,Mar. 18, 1993]AAM89960Human immune/ 1 . . . 274265/274 (96%)e−151haematopoietic 9 . . . 282266/274 (96%)antigen SEQ IDNO:17553—Homo sapiens,329 aa.[WO200157182-A2, Aug. 9,2001]


[0421] In a BLAST search of public sequence databases, the NOV18a protein was found to have homology to the proteins shown in the BLASTP data in Table 18D.
98TABLE 18DPublic BLASTP Results for NOV18aNOV18aIdentities/ProteinResidues/Similarities forAccessionProtein/Matchthe MatchedExpectNumberOrganism/LengthResiduesPortionValueCAC34689SEQUENCE 3 1 . . . 633605/695 (87%)0.0FROM PATENT210 . . . 904610/695 (87%)WO0114564—Homo sapiens(Human),1851 aa.Q91WS2HYPO-107 . . . 659390/557 (70%)0.0THETICAL 1 . . . 554450/557 (80%)62.5 KDAPROTEIN—Mus musculus(Mouse), 556 aa(fragment).Q63035VASOPRESSIN193 . . . 670324/483 (67%) e−173RECEPTOR— 1 . . . 482372/483 (76%)Rattus norvegicus(Rat), 483 aa.AAL12498CRYOPYRIN— 3 . . . 657232/709 (32%)5e−94 Homo sapiens234 . . . 914355/709 (49%)(Human), 920 aa.AAL12497CRYOPYRIN— 3 . . . 648223/658 (33%)6e−93 Homo sapiens234 . . . 848344/658 (51%)(Human), 1034aa.


[0422] PFam analysis predicts that the NOV18a protein contains the domains shown in the Table 18E.
99TABLE 18EDomain Analysis of NOV18aNOV18aIdentities/SimilaritiesExpectPfam DomainMatch Regionfor the Matched RegionValueNo Significant Matches Found



Example 19

[0423] The NOV19 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 19A.
100TABLE 19ANOV19 Sequence AnalysisSEQ ID NO:712686 bpNOV19a,CCGGCGGCGTCTCCACAGCATGAATTACCCGGGCCGCGGGTCCCCACGGAGCCCCGAGCG58626-01 DNA SequenceCATAACGGCCGAGGCGGCGGCGGCGGCGCCTGGGAGCTGGGCTCAGACGCGAGGCCAGCGTTCGGCGGCGGCGTCTGCTGCTTCGAGCACCTGCCCGGCGGGGACCCGGACGACGGCGACGTGCCCCTGGCCCTGCTGCGCGGGGAACCCGGGCTGCATTTGGCGCCGGGCACCGACGACCACAACCACCACCTCGCGCTGGACCCCTGCCTCAGTGACGAGAACTATGACTTCAGCTCCGCCGAGTCGGGCTCCTCGCTGCGCTACTACAGCGAGGGTGAGAGCGGCGGCGGCGGCAGCTCCTTGTCGCTGCACCCGCCGCAGCAGCCTCCGCTGGTCCCGACGAACTCGGGGGGCGGCGGCGCGACAGGAGGGTCCCCCGGGGAAAGGAAACGTACCCGCCTTGGCGGCCCGGCGGCCCGGCACCGCTATGAGGTAGTGACGGAGCTGGGCCCGGAGGAGGTACGCTGGTTCTACAAGGAGGACAAGAAGACCTGGAAGCCCTTCATCGGCTACGACTCGCTCCGCATCGAGCTCGCCTTCCGGACCCTGCTGCAGACCACGGGTGCCCGGCCCCAGGGCGGGGACCGGGACGGCGACCATGTGTGCTCCCCCACGGGCCCAGCCTCCAGTTCCGGAGAAGATGACGATGAGGACCGCGCCTGCGGCTTCTGCCAGAGTACGACGGGGCACGAGCCGGAGATGGTGGAGCTTGTGAACATCGAGCCTGTGTGCGTGCGGGGCGGCCTCTACGAGGTGGATGTGACCCAAGGAGAGTGCTACCCGGTGTACTGGAACCGTGCTGATAAAATACCAGTAATGCGTGGACAGTGGTTTATTGACGGCACTTGGCAGCCTCTAGAAGAGGAAGAAAGTAATTTAATTGAGCAAGAACATCTCAATTGTTTTAGGGGCCAGCAGATGCAGGAAAATTTCGATATTGAAGTGTCAAAATCCATAGATGGAAAAGATGCTGTTCATAGTTTCAAGTTGAGTCGAAACCATGTGGACTGGCACAGTGTGGATGAAGTATATCTTTATAGTGATGCAACAACATCTAAAATTGCAAGAACAGTTACCCAAAAACTGGGATTTTCTAAAGCATCAAGTAGTGGTACCAGACTTCATAGAGGTTATGTAGAAGAAGCCACATTAGAAGACAAGCCATCACAGACTACCCATATTGTATTTGTTGTGCATGGCATTGGGCAGAAAATGGACCAAGGAAGAATTATCAAAAATACAGCTATGATGAGAGAAGCTGCAAGAAAAATAGAAGAAAGGCATTTTTCCAACCATGCAACACATGTTGAATTTCTGCCTGTTGAGTGGCGGTCAAAACTTACTCTTGATGGAGACACTGTTGATTCCATTACTCCTGACAAAGTACGAGGTTTAAGGGATATGCTGAACAGCAGTGCAATGGACATAATGTATTATACTAGTCCACTTTATAGAGATGAACTAGTTAAAGGCCTTCAGCAAGAGCTGAATCGATTGTATTCCCTTTTCTGTTCTCGGAATCCAGACTTTGAAGAAAAAGGGGGTAAAGTCTCAATAGTATCACATTCCTTGGGATGTGTAATTACTTATGACATAATGACTGGCTGGAATCCAGTTCGGCTGTATGAACAGTTGCTGCAAAAGGAAGAAGAGTTGCCTGATGAACGATGGATGAGCTATGAAGAACGACATCTTCTTGATGAACTCTATATAACTAAACGACGGCTGAAGGAAATAGAAGAACGGCTTCACGGATTGAAAGCATCATCTATGACACAAACACCTGCCTTAAAATTTAAGGTAGAGAATTTCTTCTGTATGGGATCCCCATTAGCAGTTTTCTTGGCGTTGCGTGGCATCCGCCCAGGAAATACTGGAAGTCAAGACCATATTTTGCCTAGAGAGATTTGTAACCGGTTACTAAATATTTTTCATCCTACAGATCCAGTGGCTTATAGATTAGAACCATTAATACTGAAACACTACAGCAACATTTCACCTGTCCAGATCCACTGGTACAATACTTCAAATCCTTTACCTTATGAACATATGAAGCCAAGCTTTCTCAACCCAGCTAAAGAACCTACCTCAGTTTCAGAGAATGAAGGCATTTCAACCATACCAAGCCCTGTGACCTCACCAGTTTTGTCCCGCCGACACTATGGAGAATCTATAACAAATATAGGCAAAGCAAGCATATTAGGTGCTGCTAGCATTGGAAAGGGACTTGGAGGAATGTTGTTCTCAAGATTTGGACGTTCATCTACAACACAGTCATCTGAAACATCAAAAGACTCAATGGAAGATGAGAAGAAGCCAGTTGCCTCACCTTCTGCTACCACCGTAGGGACACAGACCCTTCCACATAGCAGTTCTGGCTTCCTCGATTCTGCAGTGGAGTTGGATCACAGGATTGATTTTGAACTCAGAGAAGGCCTTGTGGAGAGCCGCTATTGGTCAGCTGTCACGTCGCATACTGCCTATTGGTCATCCTTGGATGTTGCCCTTTTTCTTTTAACCTTCATGTATAAACATGAGCACGATGATGATGCAAAACCCAATTTAGATCCAATCTGAACTCTCTTGAAGGACATGAATGGCCTAAAACTGATTTTTTTTTTTTCCORF Start: ATG at 20ORF Stop: TGA at 2636SEQ ID NO:72872 aaMW at 97063.4 kDNOV19a,MNYPGRGSPRSPEHNGRGGGGGAWELGSDARPAFGGGVCCFEHLPGGDPDDGDVPLALCG58626-01 Protein SequenceLRGEPGLHLAPGTDDHNHHLALDPCLSDENYDFSSAESGSSLRYYSEGESGGGGSSLSLHPPQQPPLVPTNSGGGGATGGSPGERKRTRLGGPAARHRYEVVTELGPEEVRWFYKEDKKTWKPFIGYDSLRIELAFRTLLQTTGARPQGGDRDGDHVCSPTGPASSSGEDDDEDRACGFCQSTTGHEPEMVELVNIEPVCVRGGLYEVDVTQGECYPVYWNRADKIPVMRGQWFIDGTWQPLEEEESNLIEQEHLNCFRGQQMQENFDIEVSKSIDGKDAVHSFKLSRNHVDWHSVDEVYLYSDATTSKIARTVTQKLGFSKASSSGTRLHRGYVEEATLEDKPSQTTHIVFVVHGIGQKMDQGRIIKNTAMMREAARKIEERHFSNHATHVEFLPVEWRSKLTLDGDTVDSITPDKVRGLRDMLNSSAMDIMYYTSPLYRDELVKGLQQELNRLYSLFCSRNPDFEEKGGKVSIVSHSLGCVITYDIMTGWNPVRLYEQLLQKEEELPDERWMSYEERHLLDELYITKRRLKEIEERLHGLKASSMTQTPALKFKVENFFCMGSPLAVFLALRGIRPGNTGSQDHILPREICNRLLNIFHPTDPVAYRLEPLILKHYSNISPVQIHWYNTSNPLPYEHMKPSFLNPAKEPTSVSENEGISTIPSPVTSPVLSRRHYGESITNIGKASILGAASIGKGLGGMLFSRFGRSSTTQSSETSKDSMEDEKKPVASPSATTVGTQTLPHSSSGFLDSAVELDHRIDFELREGLVESRYWSAVTSHTAYWSSLDVALFLLTFMYKHEHDDDAKPNLDPI


[0424] Further analysis of the NOV19a protein yielded the following properties shown in Table 19B.
101TABLE 19BProtein Sequence Properties NOV19aPSort0.4555 probability located in microbody (peroxisome); 0.4500analysis:probability located in cytoplasm; 0.1000 probability located inmitochondrial matrix space; 0.1000 probability located inlysosome (lumen)SignalPNo Known Signal Sequence Predictedanalysis:


[0425] A search of the NOV19a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 19C.
102TABLE 19CGeneseq Results for NOV19aNOV19aIdentities/Protein/Residues/Similarities forGeneseqOrganism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAG64151Arabidopsis257 . . . 547104/316 (32%)1e−38thaliana156 . . . 454156/316 (48%)gravitropismprotein—Arabidopsisthaliana, 933 aa.[JP2001120279-A, May 8, 2001]AAM41595Human poly-261 . . . 548 94/301 (31%)6e−25peptide SEQ ID 52 . . . 328138/301 (45%)NO 6526−Homosapiens, 677 aa.[WO200153312-A1, Jul. 26, 2001]AAB92643Human protein119 . . . 608132/524 (25%)2e−24sequence SEQ ID226 . . . 664204/524 (38%)NO:10972—Homo sapiens,1000 aa.[EP1074617-A2,Feb. 7, 2001]AAM39809Human poly-274 . . . 548 90/288 (31%)4e−23peptide SEQ ID 3 . . . 266131/288 (45%)NO 2954—Homosapiens, 615 aa.[WO200153312-A1, Jul. 26, 2001]AAB93825Human protein404 . . . 608 76/229 (33%)6e−23sequence SEQ ID227 . . . 449113/229 (49%)NO:13636—Homo sapiens,694 aa.[EP1074617-A2,Feb. 7, 2001]


[0426] In a BLAST search of public sequence databases, the NOV19a protein was found to have homology to the proteins shown in the BLASTP data in Table 19D.
103TABLE 19DPublic BLASTP Results for NOV19aNOV19aIdentities/ProteinResidues/Similarities forAccessionProtein/Matchthe MatchedExpectNumberOrganism/LengthResiduesPortionValueO46606PHOSPHATIDIC 1 . . . 872802/876 (91%)0.0ACID- 1 . . . 875829/876 (94%)PREFERRINGPHOSPHO-LIPASE A1—Bos taurus(Bovine), 875 aa.Q9C0F8KIAA1705378 . . . 872493/495 (99%)0.0PROTEIN— 4 . . . 498494/495 (99%)Homo sapiens(Human), 498 aa(fragment).Q96LL2CDNA FLJ25408419 . . . 872453/454 (99%)0.0FIS, CLONE 1 . . . 454454/454 (99%)TST02965,HIGHLYSIMILAR TOBOS TAURUSPHOSPHATIDICACID-PREFERRINGPHOSPHO-LIPASE A1MRNA—Homosapiens (Human),454 aa.AAH18552HYPO-624 . . . 869224/246 (91%) e−130THETICAL 1 . . . 246236/246 (95%)27.3 KDAPROTEIN—Musmusculus(Mouse), 249 aa(fragment).AAL32232HYPO-122 . . . 867255/794 (32%)6e−91 THETICAL 11 . . . 750374/794 (46%)85.1 KDAPROTEIN—Caenorhabditiselegans, 753 aa.


[0427] PFam analysis predicts that the NOV19a protein contains the domains shown in the Table 19E.
104TABLE 19EDomain Analysis of NOV19aNOV19aIdentities/SimilaritiesExpectPfam DomainMatch Regionfor the Matched RegionValueDUF203: domain252 . . . 458 42/219 (19%)7.51 of 1105/219 (48%)DDHD: domain611 . . . 858 96/266 (36%)3.3e−1161 of 1236/266 (89%)



Example 20

[0428] The NOV20 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 20A.
105TABLE 20ANOV20 Sequence AnalysisSEQ ID NO:73773 bpNOV20a,GGTAAGGACACAAGATGCCAAATAGGGTAAGGAATGGTCCAGAAACCTGTGAACTCTGCG57597-01 DNA SequenceCATTGCAGGCATGCACCACCACTCCTGGCTAATTTTTTGTATTTTTAGTGCCATCGAATCCGGCTCAAACCTTTTATTTCTCTTATGTAAAAGCTGTGTACTTCAGAAAAACATGTACAGTTATCCCTGGCAGTGCCGGGGTGGGGTCTGCGCGGCCCTGGAGGCCTGGCCGGCCTTGCAGATCGCTGTGGAGAATGGCTTCGGGGGTGTGCACAGCCAGGAGAAGGCCAAGTGGCTGGGGGGTGCAGTGGAGGATTACTTCATGCGCAATGCTGACTTGGAGCTAGATGAGGTGGAAGACTTCCTTGGAGAGCTGTTGACCAACGAGTTTGATACAGTTGTGGAAGACGGGAGTCTGCCCCAGGTGAGCCAGCAACTGCAGACCATGTTCCACCACTTCCAGAGGGGTGATGGGGCTGCTCTGAGGGAGATGGCCTCCTGCATCACTCAGAGAAAATGCAAGGTCACAGCCACTGCACTTAAGACAGCTAGAGAGACTGATGAGGATGAAGATGATGTGGACAGTGTGGAAGAGATGGAGGTCACAGCTACGAATGATGGGGCTGCTACAGATGGGGTCTGCCCCCAGCCTGAACCCTCTGATCCAGACGCTCAGACTATTAAGGAAGAGGATATAGTGGAAGATGGCTGGACCATTGTCCGGAGAAAAAAATGAGTGGGGATGATTGGAAATGGCTTTGGGCCCTTATTTGCTORF Start: ATG at 15ORF Stop: TGA at 732SEQ ID NO:74239 aaMW at 26579.5 kDNOV20a,MPNRVRNGPETCELCIAGMHHHSWLIFCIFSAIESGSNLLFLLCKSCVLQKNMYSYPWCG57597-O1 Protein SequenceQCRGGVCAALEAWPALQIAVENGFGGVHSQEKAKWLGGAVEDYFMRNADLELDEVEDFLGELLTNEFDTVVEDGSLPQVSQQLQTMFHHFQRGDGAALREMASCITQRKCKVTATALKTARETDEDEDDVDSVEEMEVTATNDGAATDGVCPQPEPSDPDAQTIKEEDIVEDGWTIVRRKK


[0429] Further analysis of the NOV20a protein yielded the following properties shown in Table 20B.
106TABLE 20BProtein Sequence Properties NOV20aPSort0.3000 probability located in nucleus; 0.1000 probabilityanalysis:located in mitochondrial matrix space; 0.1000 probabilitylocated in lysosome (lumen); 0.0000 probability located inendoplasmic reticulum (membrane)SignalPNo Known Signal Sequence Predictedanalysis:


[0430] A search of the NOV20a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 20C.
107TABLE 20CGeneseq Results for NOV20aNOV20aIdentities/Protein/Residues/Similarities forGeneseqOrganism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAG81374Human AFP61 . . . 239178/179 (99%) e−101protein sequence13 . . . 191178/179 (99%)SEQ ID NO:266—Homosapiens, 191 aa.[WO200129221-A2, Apr. 26,2001]AAG57770Arabidopsis63 . . . 239 56/182 (30%)1e−13 thaliana protein18 . . . 178 94/182 (50%)Arabidopsisthaliana, 184 aa.[EP1033405-A2,Sep. 6, 2000]AAG57771Arabidopsis74 . . . 239 52/171 (30%)2e−11 thaliana protein 1 . . . 150 89/171 (51%)fragment SEQ IDNO:74487—Arabidopsisthaliana, 156 aa.[EP1033405-A2,Sep. 6, 2000]


[0431] In a BLAST search of public sequence databases, the NOV20a protein was found to have homology to the proteins shown in the BLASTP data in Table 20D.
108TABLE 20DPublic BLASTP Results for NOV20aNOV20aIdentities/ProteinResidues/Similarities forAccessionProtein/Matchthe MatchedExpectNumberOrganism/LengthResiduesPortionValueQ969E8UNKNOWN61 . . . 239178/179 (99%) e−101(PROTEIN FOR13 . . . 191178/179 (99%)MGC:20451)(PROTEIN FORIMAGE:3953868)—Homo sapiens(Human), 191 aa.Q9NAD8Y51H4A.15 1 . . . 239 66/239 (27%)5e−23 PROTEIN— 1 . . . 225122/239 (50%)Caenorhabditiselegans, 225 aa.Q06672HIGHLY ACIDIC63 . . . 238 46/177 (25%)5e−11 C-TERMINUS—79 . . . 244 82/177 (45%)Saccharomycescerevisiae (Baker'syeast), 249 aa.Q9VB10CG1454371 . . . 238 49/174 (28%)2e−10 PROTEIN—24 . . . 195 81/174 (46%)Drosophilamelanogaster(Fruit fly), 195 aa.Q9UUA9HYPOTHETICAL70 . . . 239 42/172 (24%)2e−06 HIGHLY ACIDIC22 . . . 178 83/172 (47%)C-TERMINUSPROTEIN—Schizosaccharo-myces pombe(Fission yeast),179 aa.


[0432] PFam analysis predicts that the NOV20a protein contains the domains shown in the Table 20E.
109TABLE 20EDomain Analysis of NOV20aNOV20aIdentities/SimilaritiesExpectPfam DomainMatch Regionfor the Matched RegionValueNo Significant Matches Found



Example 21

[0433] The NOV21 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 21A.
110TABLE 21ANOV21 Sequence AnalysisSEQ ID NO:757741 bpNOV21a,TTGTCTCTTTGTGTTTTCCAGACATTCTAAGTGAGACTGTCCACATCATCTAGGAAAACG57804-01 DNA SequenceTGGTGGCCCTGTCCTTAAAGATTTGTGTGCGCCACTGCAACGTGGTGAAGACCATGCAGTTTGAACCATCTACAGCTGTGTACGATGCGTGTCGAGTCATTCGGGAACGGGTGCCTGAGGCACAAACTGGGCAAGCTTCTGACTATGGACTCTTTCTTTCGGATGAAGACCCGAGGAAAGGGATTTGGCTGGAAGCGGGCAGAACACTGGATTACTACATGTTGCGGAATGGGGATATTTTGGAATATAAAAAGAAACAGAGACCTCAGAAAATCCGGATGCTGGATGGATCTGTGAAGACAGTGATGGTGGATGATTCCAAGACTGTGGGGGAGCTCCTGGTCACTATTTGTAGCAGAATAGGAATAACAAATTATGAAGAATACTCCTTAATCCAAGAAACTATTGAAGAAAAGAAAGAGGAAGGAACGGGCACACTCAAAAAAGACAGGACACTGTTACGAGATGAGAGGAAAATGGAGAAGTTGAAGGCCAAGCTGCACACAGATGATGACCTAAATTGGCTGGATCACAGCCGAACATTCAGAGAACAAGGAGTAGATGAAAACGAAACGTTGCTGCTTAGACGGAAGTTCTTTTACTCTGATCAGAATGTAGATTCGAGAGACCCCGTGCAGCTGAACTTGCTTTATGTTCAGGCACGGGATGACATCCTGAATGGCTCTCACCCTGTCTCCTTCGAGAAACCTTGTGAGTTTGGTGGATTTCAAGCCCAGATACAATTTGGACCTCATGTGGAACATAAACACAAACCTGGATTTTTAGATCTGAAGGAATTCCTGCCCAAAGAATATATCAAGCAGAGAGGAGCTGAAAAGAGGATCTTTCAGGAGCATAAGAACTGCGGAGAGATGAGTGAGATAGAAGCCAAGGTCAAGTACGTCAAACTCGCACGGTCCCTCCGCACATATGGCGTGTCCTTCTTCCTGGTGAAGGAGAAGATGAAAGGCAAGAACAAGCTGGTGCCTCGCCTGCTGGGGATCACCAAAGACTCGGTGATGCGCGTGGATGAGAAGACCAAGGAAGTGCTGCAGGAGTGGCCCCTCACCACCGTCAAGCGCTGGGCAGCCTCACCCAAGAGCTTCACACTGGATTTTGGGGAGTATCAGGAAAGCTACTATTCAGTACAAACCACCGAGGGAGAGCAGATATCCCAGCTGATTGCAGGCTACATTGACATCATCCTGAAAAAGGGAACATACGTGACATCTGTGGGGTCTCCTCATTGCACTCCACATGGCTGGTGTTCTCTCAGTGACCAAACCACTTTTCCCGGCAGGTCCACCATCTTGCAGCAGCAGTTCAACCGGACCGGGAAGGCAGAGCACGGCTCAGTGGCGCTGCCGGCCGTGATGCGCTCGGGCTCCAGCGGGCCTGAGACCTTCAACGTTGGCAGCATGCCCTCGCCACAGCAGCAGGTCATGGTTGGGCAGATGCACCGAGGCCACATGCCGCCACTGACCTCAGCCCAGCAGGCCCTGATGGGGACCATCAACACAAGCATGCACGCCGTCCAGCAGGCCCAGGATGATCTCAGTGAGCTCGACTCGCTGCCACCTCTCGGCCAGGATATGGCATCTAGGGTATGGGTTCAGAACAAAGTCGACGAATCCAAACACGAAATCCATTCTCAAGTTGATGCTATCACGGCCGGAACGGCTTCAGTTGTTAACCTCACAGCTGGTGACCCTGCAGACACTGACTACACAGCTGTGGGATGTGCGATCACCACTATTTCTTCCAACCTGACGGAGATGTCCAAGGGTGTGAAGCTATTGGCCGCCCTCATGGATGATGAGGTGGGCAGCGGGGAGGACTTGCTCAGAGCTGCCAGGACCCTCGCTGGGGCGGTGTCAGACTTGCTGAAAGCTGTGCAGCCTACTTCTGGAGAGCCTCGACAGACAGTTTTGACTGCTGCTGGCAGCATCGGACAAGCCAGTGGGGATCTTCTGAGACAGATTGGAGAGAATGAGACTGATGAGCGATTCCAGGATGTTTTAATGAGTTTGGCCAAAGCTGTTGCCAATGCAGCTGCCATGTTGGTACTAAAGGCAAAGAATGTTGCCCAAGTGGCCGAAGACACTGTCCTACAGAACAGGGTAATTGCTGCTGCCACCCAGTGTGCCCTCTCCACCTCCCAGCTTGTGGCATGTGCCAAGGTTGTGAGCCCCACTATTAGCTCCCCTGTGTGCCAGGAGCAGCTGATTGAAGCAGGGAAGCTGGTGGACCGCTCGGTGGAGAACTGTGTCCGTGCCTGCCAGGCGGCCACTACCGATAGTGAGCTCCTGAAGCAGGTCAGCGCAGCGGCCAGCGTGGTCAGCCAGGCCCTCCATGATCTCCTGCAGCATGTGCGGCAGTTTGCCAGCCGAGGCGAGCCCATCGGCCGCTACGACCAGGCTACTGACACCATCATGTGTGTCACCGAGAGCATCTTCAGCTCCATGGGTGACGCTGGTGAAATGGTGCGCCAGGCGCGGGTTCTGGCCCAAGCCACATCAGACCTCGTCAATGCCATGAGGTCAGATGCAGAAGCCGAAATCGACATGGAGAATTCAAAGAAGCTCCTGGCAGCAGCAAAACTCTTAGCTGACTCCACTGCTCGCATGGTGGAAGCTGCAAAGGGGGCTGCAGCCAACCCAGAGAATGAGGACCAGCAGCAAAGGCTGAGAGAAGCTGCAGAAGGCCTCCGGGTAGCAACCAACGCAGCTGCCCAGAATGCTATTAAGAAAAAAATTGTCAACCGACTGGAGGTTGCAGCCAAGCAGGCCGCAGCGGCAGCCACACAGACCATCGCCGCCTCCCAGAATGCAGCTGTTTCCAACAAGAACCCTGCGGCCCAGCAGCAGCTGGTCCAGAGTTGCAAGGCAGTGGCTGATCACATCCCTCAGCTGGTCCAGGGAGTGAGGGGGAGCCAAGCTCAAGCTGAAGACCTGAGTGCCCAGCTGGCTCTCATCATCTCCAGCCAGAACTTCCTCCAGCCTGGAAGCAAGATGGTGTCCTCTGCCAAAGCCGCAGTGCCCACCGTGAGTGACCAGGCCGCAGCCATGCAGCTGAGCCAGTGTGCCAAGAACCTGGCCACCAGCTTGGCGGAGCTGCGTACCGCCTCGCAGAAGGCCCATGAAGCTTGTGGTCCGATGGAAATCGATTCAGCTCTGAATACGGTGCAGACGCTTAAGAATGAACTGCAGGATGCCAAGATGGCAGCCGTGGAGAGCCAGCTGAAGCCACTTCCAGGGGAAACGCTGGAAAAATGTGCTCAGGACCTGGGAAGCACATCCAAGGCGGTGGGCTCCTCCATGGCACAGCTGCTGACCTGTGCTGCTCAAGGCAACGAACACTACACAGGGGTGGCTGCTAGAGAGACGGCCCAAGCTCTGAAAACACTGGCCCAGGCCGCCCGTGGAGTGGCTGCATCGACAACCGACCCCGCGGCCGCCCATGCCATGTTAGATTCTGCTCGAGACGTGATGGAGGGCTCCGCCATGCTCATTCAAGAGGCCAAGCAGGCCCTGATTGCACCTGGAGATGCAGAGCGTCAACAAAGACTGGCTCAGGTGGCTAAAGCCGTCTCACACTCCTTGAATAACTGCGTAAATTGCCTCCCTGGGCAGAAGGATGTGGACGTGGCCTTGAAGAGCATCGGGGAGTCCAGCAAGAAGCTQCTTGTGGATTCGCTACCTCCAAGCACGAAGCCTTTCCAGGAAGCCCAGAGTGAACTGAACCAGGCAGCAGCTGATCTGAACCAGTCTGCTGGGGAAGTGGTCCATGCCACCCGGGGCCAGAGTGGACAGTTGGCTGCAGCCTCTGGAAAGTTCAGTGATGATTTTGGTGAATTCCTCGATGCTGGCATTGAGATGGCTGGCCAAGCTCAGACAAAAGAAGACCAGATCCAAGTGATAGGGAACCTCAAGAATATCTCGATGGCATCCAGCAAGCTGCTGTTAGCTGCCAAGTCTCTCTCTGTAGATCCAGGAGCTCCCAATGCGAAAAATCTCCTGGCTGCAGCTGCAAGAGCTGTGACAGAGAGCATCAATCAACTCATCACTCTGTGTACCCAACAAGCTCCGGGCCAGAAAGAGTGCGATAATGCCCTGCGGGAGCTCGAGACTGTGAAGGGGATGTTGGACAATCCTAATGAACCTGTTAGTGACCTCTCTTACTTTGACTGCATTGAGAGTGTGATGGAAAACTCCAAGGTTCTGGGTGAATCGATGGCAGGGATTTCACAGAATGCCAAGACCGGAGACCTCCCTGCCTTTGGGGAATGTGTGGGGATTGCATCCAAGGCTCTCTGTGGGCTGACAGAGGCTGCAGCCCAGGCTGCATACTTGGTTGGCATCTCTGATCCAAACAGCCAGGCAGGCCACCAGGGCCTGGTGGACCCCATCCAGTTTGCCAGGGCTAACCAGGCCATCCAGATGGCATGCCAGAACTTGGTGGACCCTGGCAGCAGCCCATCACAGGTCCTGTCAGCCGCCACAATTGTTGCCAAGCACACGTCAGCCTTGTGCAATGCCTGCCGCATCGCCTCATCCAAGACGGCCAACCCAGTAGCCAAGAGGCACTTCGTCCAGTCAGCCAAGGAAGTCGCCAACAGCACTGCCAACCTGGTGAAGACCATCAAGGCCCTGGATGGGGATTTCTCTGAAGACAACCGCAATAAGTGTCGCATCGCCACCGCACCCTTGATTGAAGCTGTGGAGAACCTGACAGCGTTCGCCTCAAACCCTGAGTTTGTCAGCATTCCTGCCCAGATCAGCTCCGAGGGTTCCCAGGCACAGGAACCAATCCTGGTCTCAGCCAAGACCATGCTGGAGAGTTCATCGTACCTCATTCGCACTGCACGCTCTCTGGCCATCAACCCCAAAGACCCACCCACCTGGTCTGTACTGGCTGGACATTCCCATACAGTGTCCGACTCCATCAAGAGTCTCATCACTTCTATCAGGGACAAGGCCCCTGGACAGAGGGAGTGTGATTACTCCATCGATGGCATCAACCGGTGCATCCGGGACATCGAGCAGGCCTCGCTGGCCGCCGTCAGCCAGAGCCTGGCCACGAGGGACGACATCTCTGTGGAGGCCCTGCAGGAGCAGCTGACTTCGGTGGTCCAGGAAATCGGACACCTTATCGATCCCATCGCCACAGCGGCTCGGGGAGAAGCAGCTCAGCTGGGACATAAGGTGACACAACTGGCAAGCTATTTTGAGCCCTTGATCTTAGCCGCAGTTGGTGTGGCCTCCAAGATTCTTGATCATCAGCAGCAGATGACGGTGCTGGACCAGACCAAGACTCTCGCAGAGTCTGCCTTGCAGATGTTGTATGCAGCCAAAGAAGGTGGCGGAAACCCCAAGGCACAACACACCCATGACGCCATCACAGAGGCCGCCCAGTTGATGAAGGAAGCCGTGGATGACATCATGGTGACGCTGAACGAAGCTGCCAGTGAAGTGGGGCTGGTTGGGGGCATGGTGGACGCCATTGCAGAAGCCATGAGCAAGCTGGATGAAGGCACTCCTCCAGAACCAAAGGGAACATTTGTCGACTATCAGACGACTGTGGTTAAATACTCCAAAGCCATTGCGGTGACAGCTCAGGAAATGATGACTAAGTCGGTTACTAACCCGGAGGAGTTGGGAGGACTGGCTTCACAAATGACCAGTGACTATGGGCACCTGGCTTTCCAGGGCCAGATGGCAGCAGCCACGGCGGAACCAGAGGAGATCGGATTCCAGATTCGCACTCGTGTGCAGGACCTGGGCCACGGCTGTATCTTCCTGGTGCAGAAGGCAGGGGCCCTCCAGGTCTGCCCCACAGACAGCTACACCAAGAGGGAGCTGATCGAATGCGCCCGTGCCGTCACGGAAAAGGTCTCCTTGGTGCTCTCGGCTCTCCAGGCCGGGAACAAAGGAACCCAGGCATGCATTACAGCCGCCACCGCTGTGTCTGGGATCATTGCCGACCTGGACACCACCATTATGTTTGCAACAGCGGGGACGCTGAATGCAGAGAACAGTGAGACCTTCGCAGACCACAGGGAGAACATTCTCAAGACGGCCAAGGCCTTGGTAGAAGACACGAAACTACTTGTGTCAGGAGCTGCGTCCACTCCTGACAAGCTGGCCCAGGCGGCCCAGTCCTCAGCAGCCACCATCACCCAGCTCGCAGAAGTGGTCAAGCTGGGGGCAGCCAGCCTGGGCTCCGACGACCCCGAGACCCAGGTGGATTTGATCAATGCCATCAAAGATGTGGCCAAGGCCCTTTCTGATCTCATCAGTGCTACCAAGGGAGCTGCCAGCAAGCCAGTGGACGACCCTTCCATGTACCAGCTCAAGGGGGCTGCCAAGGTGATGGTGACCAATGTCACCTCGCTCCTCAAGACTGTAAAGGCAGTGGAGGATGAGGCCACCCGGGGCACCAGGGCGCTTGAGGCCACAATTGAATGCATAAAGCAGGAGCTTACGGTGTTCCAGTCAAAAGACGTACCTGAAAAGACATCATCACCTGAAGAATCCATAAGGATGACGAAAGGCATCACCATGGCAACAGCCAAAGCCGTGGCAGCTGGGAACTCATGTAGACAGGAGGACGTGATTGCTACTGCCAACCTGAGCCGGAAAGCCGTGTCAGATATGTTGACGGCTTGCAAGCAAGCATCCTTCCACCCCGATGTCAGTGACGAGGTGAGAACCAGAGCCTTGCGTTTCGGGACGGAGTGCACCCTTGGCTACTTGGACCTCCTGGAGCACGTCTTGGTGATTCTTCAGAAACCAACCCCAGAATTCAAGCAGCAGCTGGCCGCTTTCTCCAAGCGAGTCGCCGGCGCTGTGACAGAGCTCATCCAGGCGGCGGAAGCCATGAAAGGAACAGAGTGGGTGGATCCAGAAGACCCAACTGTCATTGCAGAAACAGAGTTACTGGGGGCTGCAGCATCCATCGAAGCTGCTGCTAAGAAGTTAGAGCAACTGAAGCCAAGAGCAAAACCAAAACAAGCGGATGAGACCCTGGACTTTGAGGAACAGATCTTGGAAGCTGCTAAATCCATTGCTGCTGCCACAAGCGCCCTGGTCAAATCGGCCTCAGCAGCCCAGAGGGAGCTGGTGGCCCAAGGAAAGGTGGGCTCCATCCCTGCCAATGCTGCAGACGACGGACAGTGGTCACAGGGGCTGATTTCTGCTGCCCGGATGGTGGCGGCTGCGACCAGCAGTCTCTGTGAGGCGGCCAATGCCTCCGTTCAGGGACACGCCAGCGAGGAGAAGCTCATCTCATCTGCCAAGCAGGTCGCCGCTTCCACGGCTCAGCTGCTGGTGGCCTGCAAGGTGAAGGCCGACCAGGATTCAGAGGCCATGAGGCGGCTACAGGCGGCAGGAAATGCTGTGAAAAGAGCCTCAGACAATCTTGTCCGTGCAGCCCAGAAGGCAGCTTTTGGCAAAGCTGATGACGACGATGTTGTAGTGGAAACCAAGTTTGTGGGGGGCATTGCTCAGATCATCGCCGCCCAGGAAGAAATGCTAAAGAAAGAGCGAGAACTGGAAGAAGCAAGGAAAAAACTGGCCCAAATCCGCCAGCAGCAGTATAAGTTTTTACCCACCGAGCTGAGGGAAGATGAGGGCTAAAGGTGCGAGCCCAGATGGCGAGCCCCAGGGGATGGCCCTGGCTGAAORF Start: ATG at 58ORF Stop: TAA at 7693SEQ ID NO:762545 aaMW at 271692.8 kDNOV21a,MVALSLKICVRHCNVVKTMQFEPSTAVYDACRVIRERVPEAQTGQASDYGLFLSDEDPCG57804-01 ProteinSequenceRKGIWLEAGRTLDYYMLRNGDILEYKKKQRPQKIRMLDGSVKTVMVDDSKTVGELLVTICSRIGITNYEEYSLIQETIEEKKEEGTGTLKKDRTLLRDERKMEKLKAKLHTDDDLNWLDHSRTFREQGVDENETLLLRRKFFYSDQNVDSRDPVQLNLLYVQARDDILNGSHPVSFEKACEFGGFQAQIQFGPHVEHKHKPGFLDLKEFLPKEYIKQRGAEKRIFQEHKNCGEMSEIEAKVKYVKLARSLRTYGVSFFLVKEKMKGKNKLVPRLLGITKDSVMRVDEKTKEVLQEWPLTTVKRWAASPKSFTLDFGEYQESYYSVQTTEGEQISQLIAGYIDIILKKGTYVTSVGSPHCTPHGWCSLSDQTTFPGRSTILQQQFNRTGKAEHGSVALPAVMRSGSSGPSTFNVGSMPSPQQQVMVGQMHRGHMPPLTSAQQALMGTINTSMHAVQQAQDDLSELDSLPPLGQDMASRVWVQNKVDESKHEIHSQVDAITAGTASVVNLTAGDPADTDYTAVGCAITTISSNLTEMSKGVKLLAALMDDEVGSGEDLLRAARTLAGAVSDLLKAVQPTSGEPRQTVLTAAGSIGQASGDLLRQIGENETDERFQDVLMSLAKAVANAAAMLVLKAKNVAQVAEDTVLQNRVIAAATQCALSTSQLVACAKVVSPTISSPVCQEQLIEAGKLVDRSVENCVRACQAATTDSELLKQVSAAASVVSQALHDLLQHVRQFASRGEPIGRYDQATDTIMCVTESIFSSMGDAGEMVRQARVLAQATSDLVNAMRSDAEAEIDMENSKKLLAAAKLLADSTARMVEAAKGAAANPENEDQQQRLREAAEGLRVATNAAAQNAIKKKIVNRLEVAAKQAAAAATQTIAASQNAAVSNKNPAAQQQLVQSCKAVADHIPQLVQGVRGSQAQAEDLSAQLALIISSQNFLQPGSKMVSSAKAAVPTVSDQAAAMQLSQCAKNLATSLAELRTASQKAHEACGPMEIDSALNTVQTLKNELQDAKMAAVESQLKPLPGETLEKCAQDLGSTSKAVGSSMAQLLTCAAQGNEHYTGVAARETAQALKTLAQAARGVAASTTDPAAAHAMKDSARDVMEGSAMLIQEAKQALIAPGDAERQQRLAQVAKAVSHSLNNCVNCLPGQKDVDVALKSIGESSKKLLVDSLPPSTKPFQEAQSELNQAAADLNQSAGEVVHATRGQSGELAAASGKFSDDFGEFLDAGIEMAGQAQTKEDQIQVIGNLKNISMASSKLLLAAKSLSVDPGAPNAKNLLAAAARAVTESINQLITLCTQQAPGQKECDNALRELETVKGMLDNPNEPVSDLSYFDCIESVMENSKVLGESMAGISQNAKTGDLPAFGECVGIASKALCGLTEAAAQAAYLVGISDPNSQAGHQGLVDPIQFARANQAIQMACQNLVDPGSSPSQVLSAATIVAKHTSALCNACRIASSKTANPVAKRHFVQSAKEVANSTANLVKTIKALDGDFSEDNRNKCRIATAPLIEAVENLTAFASNPEFVSIPAQISSEGSQAQEPILVSAKTMLESSSYLIRTARSLAINPKDPPTWSVLAGHSHTVSDSIKSLITSIRDKAPGQRECDYSIDGINRCIRDIEQASLAAVSQSLATRDDISVEALQEQLTSVVQEIGHLIDPIATAARGEAAQLGHKVTQLASYFEPLILAAVGVASKILDHQQQMTVLDQTKTLAESALQMLYAAKEGGGNPKAQHTHDAITEAAQLMKEAVDDIMVTLNEAASEVGLVGGMVDAIAEAMSKLDEGTPPEPKGTFVDYQTTVVKYSKAIAVTAQEMMTKSVTNPEELGGLASQMTSDYGHLAFQGQMAAATAEPEEIGFQIRTRVQDLGHGCIFLVQKAGALQVCPTDSYTKRELIECARAVTEKVSLVLSALQAGNKGTQACITAATAVSGIIADLDTTIMFATAGTLNAENSETFADHRENILKTAKALVEDTKLLVSGAASTPDKLAQAAQSSAATITQLAEVVKLGAASLGSDDPETQVDLINAIKDVAKALSDLISATKGAASKPVDDPSMYQLKGAAKVMVTNVTSLLKTVKAVEDEATRGTRALEATIECIKQELTVFQSKDVPEKTSSPEESIRMTKGITMATAKAVAAGNSCRQEDVIATANLSRKAVSDMLTACKQASFHPDVSDEVRTRALRFGTECTLGYLDLLEHVLVILQKPTPEFKQQLAAFSKRVAGAVTELIQAAEAMKGTEWVDPEDPTVIAETELLGAAASIEAAAKKLEQLKPRAKPKQADETLDFEEQILEAAKSIAAATSALVKSASAAQRELVAQGKVGSIPANAADDGQWSQSLISAARMVAAATSSLCEAANASVQGHASEEKLISSAKQVAASTAQLLVACKVKADQDSEAMRRLQAAGNAVKRASDNLVRAAQKAAFGKADDDDVVVETKFVGGIAQIIAAQEEMLKKERELEEARKKLAQIRQQQYKFLPTELREDEG


[0434] Further analysis of the NOV21a protein yielded the following properties shown in Table 21B.
111TABLE 21BProtein Sequence Properties NOV21aPSort0.5964 probability located in mitochondrial matrix space;analysis:0.3037 probability located in mitochondrial inner membrane;0.3037 probability located in mitochondrial intermembranespace; 0.3037 probability located in mitochondrial outermembraneSignalPNo Known Signal Sequence Predictedanalysis:


[0435] A search of the NOV21a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 21C.
112TABLE 21CGeneseq Results for NOV21aIdentities/NOV21aSimilaritiesProtein/Residues/for theGeneseqOrganism/LengthMatchMatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAB41087Human ORFX  1 . . . 25431913/25460.0ORF851 poly-(75%)peptide sequence  1 . . . 25402231/2546SEQ ID NO:(87%)1702—Homosapiens,2541 aa.[WO200058473-A2, Oct. 5, 2000]AAM39312Human poly-1381 . . . 25451161/11650.0peptide SEQ ID(99%)NO 2457—Homo  1 . . . 11651163/1165sapiens, 1165 aa.(99%)[WO200153312-A1, Jul. 26, 2001]AAM79794Human protein1378 . . . 25451156/11680.0SEQ ID NO(98%)3440—Homo 10 . . . 11771160/1168sapiens, 1177 aa.(98%)[WO200157190-A2, Aug. 9,2001]AAM41098Human poly-1378 . . . 25451156/11680.0peptide SEQ ID(98%)NO 6029—Homo 10 . . . 11771160/1168sapiens, 1177 aa.(98%)[WO200153312-A1, Jul. 26, 2001]AAM41079Human poly-1378 . . . 25451156/11680.0peptide SEQ ID(98%)NO 6010—Homo 10 . . . 11771160/1168sapiens, 1177 aa.(98%)[WO200153312-A1, Jul. 26, 2001]


[0436] In a BLAST search of public sequence databases, the NOV21a protein was found to have homology to the proteins shown in the BLASTP data in Table 21D.
113TABLE 21DPublic BLASTP Results for NOV21aIdentities/NOV21aSimilaritiesProteinResidues/for theAccessionProtein/MatchMatchedValueNumberOrganism/LengthResiduesPortionExpectQ9Y490Talin—Homo  1 . . . 25431910/25460.0sapiens (Human),(75%)2541 aa.  1 . . . 25402230/2546(87%)P26039Talin—Mus  1 . . . 25431907/25460.0musculus(74%)(Mouse), 2541 aa.  1 . . . 25402230/2546(86%)Q9UPX3KIAA1027 853 . . . 25431262/16940.0PROTEIN—(74%)Homo (fragment).  1 . . . 16941483/1694(87%)Q9VSL8CG6831  1 . . . 25321197/25630.0PROTEIN(46%)(TALIN)—  1 . . . 25341707/2563Drosophila(65%)melanogaster(Fruit fly),2836 aa.Q9Y4G6KIAA03201597 . . . 2545947/9490.0PROTEIN—(99%)Homo sapiens 1 . . . 949948/949(Human), 949 aa(99%)(fragment).


[0437] PFam analysis predicts that the NOV21a protein contains the domains shown in the Table 21E.
114TABLE 21EDomain Analysis of NOV21aIdentities/SimilaritiesNOV21afor theExpectPfam DomainMatch RegionMatched RegionValueubiquitin: domain 1 of 164 . . . 88  8/27 (30%)4.3 20/27 (74%)Band_41: domain 1 of 1123 . . . 316 67/211 (32%)1.3e−92172/211 (82%)IRS: domain 1 of 1312 . . . 404 19/109 (17%)1.2 46/109 (42%)I_LWEQ: domain 1 of 5674 . . . 768 31/98 (32%)11 59/98 (60%)transport_prot: domain667 . . . 814 24/182 (13%)101 of 1 88/182 (48%)I_LWEQ: domain 2 of 5852 . . . 894 18/47 (38%)2.4e+02 31/47 (66%)Vinculin: domain 1 of 1860 . . . 903 12/48 (25%)1.3 30/48 (62%)I_LWEQ: domain 3 of 5925 . . . 984 21/62 (34%)5.9e+04 37/62 (60%)TP_methylase: domain 861 . . . 1036 26/226 (12%)81 of 1105/226 (46%)Apolipoprotein: domain 981 . . . 1229 48/288 (17%)3.51 of 1141/288 (49%)CAP: domain 1 of 1 917 . . . 1354 94/557 (17%)4.4209/557 (38%)I_LWEQ: domain 4 of 51529 . . . 1545 10/17 (59%)56 13/17 (76%)STAT: domain 1 of 11660 . . . 1821 35/211 (17%)8.2 95/211 (45%)LEA: domain 1 of 11768 . . . 1834 15/76 (20%)7 42/76 (55%)Histone_HNS: domain2232 . . . 2356 29/143 (20%)3.71 of 1 63/143 (44%)I_LWEQ: domain 5 of 52345 . . . 2536100/202 (50%) 2e−101183/202 (91%)



Example 22

[0438] The NOV22 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 22A.
115TABLE 22ANOV22 Sequence AnalysisSEQ ID NO:772214 bpNOV22a,ATTCCTCCCTGCCCCTCGTGCAGCCGCTGCCATGGCCCAGACACTGCAGATGGAGATCCG57551-01 DNA SequenceCCGAACTTCGGCAACAGCATCCTGGAGTGCCTCAATGAACAGCGGCTGCAGGGCCTGTACTGTGACGTGTCAGTGGTGGTCAAGGGCCATGCCTTCAAGGCCCACCGGGCCGTGCTTGCTGCCAGCAGCTCCTACTTCCGGGACCTGTTCAACAACAGCCGCAGCGCCGTGGTGGAGCTGCCGCCGGCTGTGCAGCCCCAGTCTTTCCAGCAGATCCTCAGCTTCTGCTACACGGGCCGGCTGAGCATGAACGTGGGCGACCAGTTCCTGCTCATGTACACGGCTGGCTTCCTGCAGATCCAGGAGATCATGGAGAAGGGCACCGAGTTCTTCCTCAAGGTGAGCTCCCCGAGCTGCGACTCCCAGGGCCTGCATGCGGAGGAGGCCCCATCGTCGGAGCCCCAGAGCCCCGTGGCGCAGACATCGGGCTGGCCAGCCTGTAGCACCCCGCTGCCCCTCGTGTCGCGGGTGAAGACGGAGCAGCAGGAGTCGGACTCCGTGCAGTGCATGCCCGTGGCCAAGCGGCTGTGGGACAGTGGCCAGAAGGAGGCTGGGGGCGGCGGCAATGGCAGCCGCAAGATGGCCAAGTTCTCCACGCCGGACCTGGCTGCCAACCGGCCTCACCAGCCCCCGCCACCCCAACAGGCTCCGGTGGTGGCAGCAGCCCAGCCCGCCGTGGCTGCGGGAGCAGGGCAGCCAGCCGGTGGGGTGGCAGCAGCAGGGGGTGTGGTGAGTGGGCCCAGCACGTCGGAGCGGACCAGCCCAGGCACCTCAAGCGCCTACACCAGCGACAGCCCTGGCTCCTACCACAATGAGGAGGACGAGGAGGAGGATGGTGGCGAGGAGGGCATGGATGAGCAGTACCGGCAGATCTGCAACATGTACACCATGTACAGCATGATGAACGTCGGCCAGACAGCCGAGAAGGTGGAGGCCCTCCCGGAGCAGGTAGCCCCCGAGTCCCGAAATCGCATCCGGGTTCGGCAAGACCTGGCGTCTCTCCCGGCTGAACTTATCAACCAGATTGGGAACCGCTGCCACCCCAAGCTCTACGACGAGGGCGACCCCTCTGAGAAGCTGGAGCTGGTGACAGGCACCAACGTGTACATCACAAGGGCGCAGCTGATGAACTGCCACGTCAGCGCAGGCACGCGGCACAAGGTCCTACTGCGGCGGCTCCTGGCCTCCTTCTTTGACCGGAACACGCTGGCCAACAGCTGCGGCACCGGCATCCGCTCTTCTACCAACGATCCCCGTCGGAAGCCCCTGGACAGCCGCGTGCTCCACGCTGTCAAGTACTACTGCCAGAACTTCGCCCCCAACTTCAAGGAGAGCGAGATGAATGCCATCGCGGCCGACATGTGCACCAACGCCCGCCGCGTCGTGCGCAAGAGCTGGATGCCCAAGGTCAAGGTGCTCAAGGCTGAGGATGACGCCTACACCACCTTCATCAGTGAAACGGGCAAGATCGAGCCGGACATGATGGGTGTGGAGCATGGCTTCGAGACCGCCAGCCACGAGGGCGAGGCGGGTCCCATCGCTGAAGCCCTGCAGTAACCCGCCCAGCCTCCCGCGGGGCCGCACACTTCCCCTCCCAACACACACACACACCTGCCATCTTGGTCATGAGCTACTGTCTGTCCCTCCCCAGGACCCGCGGTGGGTGCTGCATGTTCCCGGCCCTCTGCCCCTCCTGTCCTACCCCCTTTCCCCACCGAGAGCTGGGCCGGGAGAGGACCGCAGGGCAGGTGGCGTGAGGTCCGTGTTGCCTTCTTTAACACACACTCGTGCAGTGGGGGAGTTCTGGCTCCCCAACCTAACCCCTAGCCGTCATCTCCACACTCACCAGGCCCACCAGGGGAGGGGGCTGGCCTGGGGGTCTTGGGAAGGCCCCTCCCCAGGCCTTAGGCCACCTCGCGGAAGCCTTCAGCCTCCGCCCCTCACTGCAGCCCCTTGGGACTTGAGGGGGGCCCCAGGGGTTCTCAGGACCCCTCCCACCACCTCCCAGTGCTTCCACGTCTCCAAAAGCGCCTTCCTGTCACCCTCGTCTATCCCTGCGCCTGGGGGCTGGGGTAGGCGAGGCCGTGGGGACTACCCATTTTATAGCTGGGGAAACAGGCTCCGAGAAATTGCACAACCGACCTCAGGTGGCCGGCORF Start: ATG at 32ORF Stop: TAA at 1613SEQ ID NO:78527 aaMW at 57283.8 kDNOV22a,MAQTLQMEIPNFGNSILECLNEQRLQGLYCDVSVVVKGHAFKAHRAVLAASSSYFRDLCG57551-01 Protein SequenceFNNSRSAVVELPAAVQPQSFQQILSFCYTGRLSMNVGDQFLLMYTAGFLQIQEIMEKGTEFFLKVSSPSCDSQGLHAEEAPSSEPQSPVAQTSGWPACSTPLPLVSRVKTEQOESDSVQCMPVAKRLWDSGQKEAGGGGNGSRKMAKFSTPDLAANRPHQPPPPQQAPVVAAAQPAVAAGAGQPAGGVAAAGGVVSGPSTSERTSPGTSSAYTSDSPGSYHNEEDEEEDGGEEGMDEQYRQICNMYTMYSMMNVGQTAEKVEALPEQVAPESRNRIRVRQDLASLPAELINQIGNRCHPKLYDEGDPSEKLELVTGTNVYITRAQLMNCHVSAGTRHKVLLRRLLASFFDRNTLANSCGTGIRSSTNDPRRKPLDSRVLHAVKYYCQNFAPNFKESEMNAIAADMCTNARRVVRKSWMPKVKVLKAEDDAYTTFISETGKIEPDMMGVEHGFETASHEGEAGPIAEALQ


[0439] Further analysis of the NOV22a protein yielded the following properties shown in Table 22B.
116TABLE 22BProtein Sequence Properties NOV22aPSort0.6000 probability located in nucleus; 0.1000 probabilityanalysis:located in mitochondrial matrix space; 0.1000 probabilitylocated in lysosome (lumen); 0.0000 probability located inendoplasmic reticulum (membrane)SignalPNo Known Signal Sequence Predictedanalysis:


[0440] A search of the NOV22a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 22C.
117TABLE 22CGeneseq Results for NOV22aNOV22aIdentities/Protein/Residues/Similarities forGeneseqOrganism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAB41621Human ORFX300 . . . 527228/228 e−131ORF1385 poly-(100%)peptide sequence 1 . . . 228228/228SEQ ID NO:(100%)2770—Homosapiens, 228 aa.[WO200058473-A2, Oct. 5, 2000]ABB17117Human nervous409 . . . 50164/947e−29 system related(68%)polypeptide SEQ 1 . . . 9373/94ID NO 5774—(77%)Homo sapiens,190 aa.[WO200159063-A2, Aug. 16,2001]AAG78615Human zinc 5 . . . 159 62/1642e−25 finger tran-(37%)scription factor 7 . . . 170 92/164BioZFTF45—(55%)Homo sapiens,413 aa.[CN1299825-A,Jun. 20, 2001]AAY73351HTRM clone 7 . . . 291 83/2918e−18 1484257 protein(28%)[WO9957144-A2, 1 . . . 277124/291Nov. 11, 1999](42%)AAM41058Human poly- 7 . . . 291 84/2952e−17 peptide SEQ ID(28%)NO 5989—Homo 2 . . . 271123/295sapiens, 804 aa.(41%)[WO200153312-A1, Jul. 26, 2001]


[0441] In a BLAST search of public sequence databases, the NOV22a protein was found to have homology to the proteins shown in the BLASTP data in Table 22D.
118TABLE 22DPublic BLASTP Results for NOV22aNOV22aIdentities/ProteinResidues/SimilaritiesAccessionProtein/Matchfor theExpectNumberOrganism/LengthResiduesMatched PortionValueQ96RE7NAC11 . . . 527526/527 (99%)0.0PROTEIN—1 . . . 527526/527 (99%)Homo sapiens(Human), 527 aa.O35260NAC-1 1 . . . 527462/530 (87%)0.0PROTEIN—1 . . . 514475/530 (89%)Rattus norvegicus(Rat), 514 aa.Q9CZ724930511N13R1K1 . . . 527462/530 (87%)0.0PROTEIN—Mus1 . . . 514476/530 (89%)musculus(Mouse), 514 aa.Q96BF6SIMILAR TO1 . . . 501289/522 (55%)e−140RIKEN CDNA1 . . . 478335/522 (63%)0610020I02GENE—Homosapiens (Human),587 aa.AAH22103RIKEN CDNA1 . . . 485281/502 (55%)e−1390610020I021 . . . 459327/502 (64%)GENE—Musmusculus(Mouse), 586 aa.


[0442] PFam analysis predicts that the NOV22a protein contains the domains shown in the Table 22E.
119TABLE 22EDomain Analysis of NOV22aIdentities/NOV22aSimilarities forExpectPfam DomainMatch Regionthe Matched RegionValueBTB: domain 1 of 114 . . . 12440/143 (28%)6.2e−2388/143 (62%)



Example 23

[0443] The NOV23 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 23A.
120TABLE 23ANOV23 Sequence AnalysisSEQ ID NO:791497 bpNOV23a,b ATGGCCACTGCACAGGTGGAACTGGTGCAGGGTGGTCCCCGGGCTCCAGTAGGGGAGACG57411-01 DNA SequenceAGCTGGAGCTCGTCCTGTCGAACCTGCAGGCAGACGTCCTGGAGTTGCTGCTGGAGTTTGTCTACACGGGCTCCCTGGTCATCGACTCGGCCAACGCCAAGACACTGCTGGAGGCGGCCAGCAAGTTCCAGTTCCACACCTTCTGCAAAGTCTGCGTGTCCTTTCTCGAGAAGCAGCTGACGGCCAGCAACTGCCTGGGCGTGCTGGCCATGGCCGAGGCCATGCAGTGCAGCGAGCTCTACCACATGGCCAAGGCCTTCGCGCTGCAGATCTTCCCCGAGGTGGCCGCCCAGGAGGAGATCCTCAGCATCTCCAAGGACGACTTCATCGCCTACGTCTCCAACGACAGCCTCAACACCAAGGCTGAGGAGCTGGTGTACGAGACAGTCATCAAGTGGATCAAGAAGGACCCCGCGACACGCACACAGCTGCAGTACGCGGCTGAGCTCCTGGCCGTGGTCCGCCTCCCCTTCATCCACCCCAGCTACCTGCTCAATGTGGTTGACAATGAAGAGCTGATCAAGTCATCAGAAGCCTGCCGGGACCTGGTGAACGAGGCCAAACGCTACCATATGCTGCCCCACGCCCGCCAGGAGATGCAGACGCCCCGAACCCGGCCGCGCGTCCCTGCAGGTGTGGCTGAGGTCATCGTCTTGGTTGGGGGCCGTCAGATGGTGGGGATGACCCAGCGCTCGCTGGTGGCCGTCACCTGCTGGAACCCGCAGAACAACAAGTGGTACCCCTTGGCCTCGCTGCCCTTCTATGACCGCGAGTTCTTCAGTGTAGTGAGTGCAGGGGACAACATCTACCTCTCAGGTGGGATGGAATCAGGGGTGACGCTGGCTGATGTCTGGTGCTACATGTCCCTGCTTGATAACTGGAACCTCGTCTCCAGAATGACAGTCCCCCGCTGTCGGCACAATAGCCTCGTCTACGATGGGAAGATTTACACCCTCGGGGGACTTGGCGTGGCAGGCAACGTGGACCACGTGGAGGTCCCTGCAGGTGTGGCTGAGGTCATCGTCTTGGTTGGGGGCCGTCAGATGGTGGGGATGACCCAGCGCTCGCTGGTGGCCGTCACCTGCTGGAACCCGCAGAACAACAAGTGGTACCCCTTGGCCTCGCTGGGTGGGATGGAATCAGGGGTGACGCTGGCTGATGTCTGGTGCTACATGTCCCTGCTTGATAACTGGAACCTCGTCTCCAGAATGACAGTCCCCCGCTGTCGGCACAATAGCCTCGTCTACGATGGGAAGATTTACACCCTCGGGGGACTTGGCGTGGCAGGCAACGTGGACCACGTGGAGGCCTACGAGCCCACAACCAACACATGGACCCTCCTCCCCCACATGCCCTGCCCTGTGTTCAGACACGGCTGCGTCGTGATAAAGAAATATATTCAAAGCGGCTGACATCAGCAGAAAGCCCACGATAAGACTORF Start: ATG at 1ORF Stop: TGA at 1468SEQ ID NO:80489 aaMW at 54208.2 kDNOV23a,MATAQVELVQGGPRAPVGEKLELVLSNLQADVLELLLEFVYTGSLVIDSANAKTLLEACG57411-01 Protein SequenceASKFQFHTFCKVCVSFLEKQLTASNCLGVLAMAEAMQCSELYHMAKAFALQIFPEVAAQEEILSISKDDFIAYVSNDSLNTKAEELVYETVIKWIKKDPATRTQLQYAAELLAVVRLPFIHPSYLLNVVDNEELIKSSEACRDLVNEAKRYHMLPHARQEMQTPRTRPRVPAGVAEVIVLVGGRQMVGMTQRSLVAVTCWNPQNNKWYPLASLPFYDREFFSVVSAGDNIYLSGGMESGVTLADVWCYMSLLDNWNLVSRMTVPRCRHNSLVYDGKIYTLGGLGVAGNVDHVEVPAGVAEVIVLVGGRQMVGMTQRSLVAVTCWNPQNNKWYPLASLGGMESGVTLADVWCYMSLLDNWNLVSRMTVPRCRHNSLVYDGKIYTLGGLGVAGNVDHVEAYEPTTNTWTLLPHMPCPVFRHGCVVIKKYIQSG


[0444] Further analysis of the NOV23a protein yielded the following properties shown in Table 23B.
121TABLE 23BProtein Sequence Properties NOV23aPSort0.6500 probability located in cytoplasm; 0.2271 probabilityanalysis:located in lysosome (lumen); 0.1000 probability located inmitochondrial matrix space; 0.0000 probability located inendoplasmic reticulum (membrane)SignalPNo Known Signal Sequence Predictedanalysis:


[0445] A search of the NOV23a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 23C.
122TABLE 23CGeneseq Results for NOV23aNOV23aIdentities/Protein/Residues/Similarities forGeneseqOrganism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAB40940Human ORFX19 . . . 351317/333 (95%) e−180ORF704 poly- 4 . . . 334320/333 (95%)peptide sequenceSEQ ID NO:1408—Homosapiens, 335 aa.[WO200058473-A2, Oct. 5, 2000]AAM38711Human poly-22 . . . 472151/488 (30%)2e−61 peptide SEQ ID78 . . . 559222/488 (44%)NO 1856—Homosapiens, 574 aa.[WO200153312-A1, Jul. 26, 2001]AAB43090Human ORFX22 . . . 468150/491 (30%)3e−59 ORF2854 poly- 9 . . . 487241/491 (48%)peptide sequenceSEQ ID NO:5708—Homosapiens, 506 aa.[WO200058473-A2, Oct. 5, 2000]AAM38956Human poly-22 . . . 468149/491 (30%)1e−58 peptide SEQ ID 90 . . . 568240/491 (48%)NO 2101—Homosapiens, 587 aa.[WO200153312-A1, Jul. 26, 2001]AAM94018Human stomach25 . . . 470148/490 (30%)3e−56 cancer expressed76 . . . 553231/490 (46%)polypeptide SEQID NO 106—Homo sapiens,568 aa.[WO200109317-A1, Feb. 8, 2001]


[0446] In a BLAST search of public sequence databases, the NOV23a protein was found to have homology to the proteins shown in the BLASTP data in Table 23D.
123TABLE 23DPublic BLASTP Results for NOV23aNOV23aIdentities/ProteinResidues/SimilaritiesAccessionProtein/Matchfor theExpectNumberOrganism/LengthResiduesMatched PortionValueQ96CT2HYPO- 19 . . . 489390/507 (76%)0.0THETICAL203 . . . 707406/507 (79%)76.8 KDAPROTEIN—Homo sapiens(Human), 707 aa(fragment).Q96PW7KIAA1921 19 . . . 489390/507 (76%)0.0PROTEIN— 41 . . . 545406/507 (79%)Homo sapiens(Human), 545 aa(fragment).Q96BF0SIMILAR 19 . . . 351329/333 (98%)0.0TO HYPO-172 . . . 502330/333 (98%)THETICALPROTEINFLJ14106—Homo sapiens (Human), 503 aa.Q9D5K34930429H24RIK 33 . . . 485165/492 (33%)2e−66PROTEIN— 1 . . . 477248/492 (49%)Mus musculus(Mouse), 484 aa.Q9UH77Kelch-like protein 22 . . . 468150/491 (30%)1e−583—Homo sapiens 90 . . . 568241/491 (48%)(Human), 587 aa.


[0447] PFam analysis predicts that the NOV23a protein contains the domains shown in the Table 23E.
124TABLE 23EDomain Analysis of NOV23aIdentities/NOV23aSimilarities forExpectPfam DomainMatch Regionthe Matched RegionValueBTB: domain 1 of 1 4 . . . 7924/143 (17%)3.7 53/143 (37%)Kelch: domain 1 of 4223 . . . 272 9/50 (18%)0.94  28/50 (56%)Kelch: domain 2 of 4275 . . . 320 11/47 (23%)0.016 27/47 (57%)Kelch: domain 3 of 4322 . . . 396 14/75 (19%)3.3e−05 44/75 (59%)Kelch: domain 4 of 4426 . . . 471 19/47 (40%)7.2e−10 35/47 (74%)



Example 24

[0448] The NOV24 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 24A.
125TABLE 24ANOV24 Sequence AnalysisSEQ ID NO:814268 bpNOV24a,ATGACCTGGGACACAGCTCTCTGGACCTCAGTTTTTCTGATTGGGCTCCTTCCTACCCCG57399-01 DNA SequenceTTGGTTTCGCTAATTGCATCCTCCAGACTTCTGGTAAAATGTGTACTTTAAGAGGTAGATACCCCCAGCCCCCACAACCACCTCTCTGCTTGTCTCCCCTAGTCCACCAGCTCCGACCAGCAGACATCAAAGTGGTGGCCGCCCTGGGTAATGATGAAACCTTCCAGGAAAGTGGTGCAGGGCAGCTAAGTGAGCCTGACCCCAGGCAGTGGTCCTGGCCACAGGCCTGCTTGCCTGGGGTAAAAAAGGAAATGCAAGATGTGGTAGGTGAGAGAACGCCGAGCCGTCGCCGCAGCCTCCGCCGCCGAGAAGCCCTTGTTCCCGCTGCTGGGAAGGAGAGTCTGTGCCGACAAGATATTTTCATTTCCTTGTTGGAAATTATCAAGCATTTTCCTCCCTCCCCTCAGGACATCAACCTGGAGAAAGACTGGAAGCTGGTCACACTCTTCATTGGGGTCAACGACTTGTGTCATTACTGTCCACTTGTTCAGGGCCCCGTTATAGACCTGGGTGGGATGGATACCCTCCACTCCCTGCAGCTCCCAAGGGCTTTCGTCAACGTGGTGGAGGTCATGGAGCTGGCTAGCCTGTACCAGGGCCAAGGCGGGAAATGTGCCATGCTGGCAGCTCAGGAAGCCTGGAACAGCCTCCTGGCCTCCAGCAGGTACAGTGAGCAGGAGTCCTTCACCGTGGTTTTCCAGCCTTTCTTCTATGAGACCACCCCATCTGACCCCCGACTCCAGGATTCTACCACGCTGGCCTGGCATCTCTGGAATAGGATGATGGAGCCAGCAGGAGAGAAAGATGAGCCATTGAGTGTAAAACACGGGAGGCCAATGAAGTGTCCCTCTCAGGAGAGCCCCTATCTGTTCAGCTACAGAAACAGCAACTACCTGACCAGACTGCAGAAACCCCAAGACAAGCTTGTAAGAGAAGGAGCGGAAATCAGATGTCCTGACAAAGACCCCTCCGATACGGTTCCCACCTCAGTTCATAGGCTGAAGCCGGCTGACATCAACGTAATTGGAGCCCTGGGTGACTCTCTCACGGCAGGCAATGGGGCCGGGTCCACACCTGGGAACGTCTTGGACGTCTTGACTCAGTACCGAGGCCTGTCCTGGAGCGTCGGCGGAGATGAGAACATCGGCACCGTTACCACCCTGGCAGACATCCTCCGGGAATTCAACCCTTCCCTGAAGGGCTTCTCTGTTGGCACTGGGAAAGAAACCAGTCCTAATGCCTTCTTAAACCAGGCTGTGGCAGGAGGCCGAGCTGAGCAGGCCAGGAGGCTGGTGGACCTGATGAAGAATGACACGAGGATACACTTTCAGGAAGACTGGAAGATAATAACCCTGTTTATAGGCGGCAATGACCTCTGTGATTTCTGCAATGATCTGGTACACTATTCTCCCCAGAACTTCACAGACAACATTGGAAAGGCCCTGGACATCCTCCATGCTGAGTCTCAGGTTCCTCGGGCATTTGTGAACCTGGTGACGGTGCTTGAGATCGTCAACCTGAGGGAGCTGTACCAGGAGAAAAAAGTCTACTGCCCAAGGATGATCCTCAGGTCACTGTGTCCCTGTGTCCTGAAGTTTGATGATAACTCAACAGAACTTGCTACCCTCATCGAATTCAACAAGAAGTTTCAGGAGAAGACCCACCAACTGATTGAGAGTGGGCGATATGACACAAGGGAAGATTTTACTGTGGTTGTGCAGCCGTTCTTTGAAAACGTGGACATGCCAAAGACCCAGGAAGGATTGCCTGACAACTCTTTCTTCGCTCCTGACTGTTTCCACTTCAGCAGCAAGTCTCACTCCCGAGCAGCCAGTGCTCTCTGGAACAATATGCTGGAGCCTGTTGGCCAGAAGACGACTCGTCATAAGTTTGAAAACAAGATCAATATCACATGTCCGTCACAGGTCCAGCCGTTTCTGAGGACCTACAAGAACAGCATGCAGGGTCATGGGACCTGGCTGCCATGCAGGGACAGAGCCCCTTCTGCCTTGCACCCTACCTCAGTGCATGCCCTGAGACCTGCAGACATCCAAGTTGTGGCTGCTCTGGGGGATTCTCTGACCGCTGGCAATGGAATTGGCTCCAAACCAGACGACCTCCCCGATGTCACCACACAGTATCGGGGACTGTCATACAGTGCAGGAGGGGACGGCTCCCTGGAGAATGTCACCACCTTACCTAGTTCTATCCTTCGCGAGTTTAACAGAAACCTCACAGGCTACGCCGTCGGCACGGGTGATGCCAATGACACGAATGCATTCCTCAATCAAGCTGTTCCCGGAGCAAAGGCTAGGGATCTTATGAGCCAAGTCCAAACTCTGATGCAGAAGATGAAAGATGATCATAGAGTAAATTTCCATGAAGACTGGAAGGTCATCACAGTGCTGATCGGAGGCAGCGATTTATGTGACTACTGCACAGATTCGAATCTGTATTCTGCAGCCAACTTTGTTCACCATCTCCGCAATGCCTTGGACGTCCTCCATAGAGAGGTGCCCAGAGTCCTGGTCAACCTCGTGGACTTCCTGAACCCCACTATCATGCGGCAGGTGTTCCTGGGAAACCCAGACAAGTGCCCAGTGCAGCAGGCCAGCGTTTTGTGTAACTGCGTTCTGACCCTGCGGGAGAACTCCCAAGAGCTAGCCAGGCTGGAGGCCTTCAGCCGAGCCTACCAGAGCAGCATGCGCGAGCTGGTGGGGTCAGGCCGCTATGACACGCAGGAGGACTTCTCTGTGGTGCTGCAGCCCTTCTTCCAGAACATCCAGCTCCCTGTCCTGCAGGATGGGCTCCCAGATACGTCCTTCTTTGCCCCAGACTGCATCCACCCAAATCAGAAATTCCACTCCCAGCTGGCCAGACCCCTTTGGACCAATATGCTTGAACCACTTGGAAGCAAAACAGAGACCCTGGACCTGAGAGCAGAGATGCCCATCACCTGTCCCACTCAGAATGAGCCCTTCCTGAGAACCCCTCGGAATAGTAACTACACGTACCCCATCAAGCCAGCCATTGAGAACTGGGGCAGTGACTTCCTGTGTACAGAGTGGAAGGCTTCCAATAGTGTTCCAACCTCTGTCCACCAGCTCCGACCAGCAGACATCAAAGTGGTGGCCGCCCTGGGTGACTCTCTGACTACAGCAGTGGGAGCTCGACCAAACAACTCCAGTGACCTACCCACATCTTGGAGGGGACTCTCTTGGAGCATTGGAGGGGATGGGAACTTGGAGACTCACACCACACTGCCCAGTATTCTGAAGAAGTTCAACCCTTACCTCCTTGGCTTCTCTACCAGCACCTGGGAGGGGACAGCAGGACTAAATGTGGCAGCGGAAGGGGCCAGAGCTAGGAGGGACATGCCAGCCCAGGCCTGGGACCTGGTAGAGCGAATGAAAAACAGCCCCATACACTTTCAGGAAGACTGGAAGATAATAACCCTGTTTATAGGCGGCAATGACCTCTGTGATTTCTGCAATGATCTGGTAGGTGAATATGTTCAGCACATCCAACAGGCCCTGGACATCCTCTCTGAGGAGCTCCCAAGGGCTTTCGTCAACGTGGTGGAGGTCATGGAGCTGGCTAGCCTGTACCAGGGCCAAGGCGGGAAATGTGCCATGCTGGCAGCTCAGAACAACTGCACTTGCCTCAGACACTCGCAAAGCTCCCTGGAGAAGCAAGAACTGAAGAAAGTGAACTGGAACCTCCAGCATGGCATCTCCAGTTTCTCCTACTGGCACCAATACACACAGCGTGAGGACTTTGCGGTTGTGGTGCAGCCTTTCTTCCAAAACACACTCACCCCACTGAACAGAGGGGACACTGACCTCACCTTCTTCTCCGAGGACTGTTTTCACTTCTCAGACCGCGGGCATGCCGAGATGGCCATCGCACTCTGGAACAACATGCTGGAACCAGTGGGCCGCAAGACTACCTCCAACAACTTCACCCACAGCCGAGCCAAACTCAAGTGCCCCTCTCCTGTGAGTCCTTACCTCTACACCCTGCGGAACAGCCGATTGCTCCCAGACCAGGCTGAAGAAGCCCCCGAGGTGCTCTACTGGGCTGTCCCAGTGGCAGCGGGAGTCGGCCTTGTGGTGGGCATCATCGGGACAGTGGTCTGGAGGTGCAGGAGAGGTGGCCGGAGGGAAGATCCTCCAATGAGCCTGCGCACTGTGGCCCTCTAGGCCCGGGGORF Start: ATG at 1ORF Stop: TAG at 4258SEQ ID NO:821419 aaMW at 158435.1 kDNOV24a,MTWDTALWTSVFLIGLLPTLGFANCILQTSGKMCTLRGRYPQPPQPPLCLSPLVHQLRCG57399-01 ProteinSequencePADIKVVAALGNDETFQESGAGQLSEPDPRQWSWPQACLPGVKKEMQDVVGERTPSRRRSLRRREALVPAAGKESLCRQDIFISLLEIIKHFPPSPQDINLEKDWKLVTLFIGVNDLCHYCPLVQGPVIDLGGMDTLHSLQLPRAFVNVVEVMELASLYQGQGGKCAMLAAQEAWNSLLASSRYSEQESFTVVFQPFFYETTPSDPRLQDSTTLAWHLWNRMMEPAGEKDEPLSVKHGRPMKCPSQESPYLFSYRNSNYLTRLQKPQDKLVREGAEIRCPDKDPSDTVPTSVHRLKPADINVIGALGDSLTAGNGAGSTPGNVLDVLTQYRGLSWSVGGDENIGTVTTLADILREFNPSLKGFSVGTGKETSPNAFLNQAVAGGRAEQARRLVDLMKNDTRIHFQEDWKIITLFIGGNDLCDETNDLVHYSPQNFTDNTGKALDILHAESQVPRAFVNLVTVLEIVNLRELYQEKKVYCPRMILRSLCPCVLKFDDNSTELATLIEFNKKFQEKTHQLIESGRYDTREDFTVVVQPFFENVDMPKTQEGLPDNSFFAPDCFHFSSKSHSRAASALWNNMLEPVGQKTTRHKFENKINITCPSQVQPFLRTYKNSMQGHGTWLPCRDRAPSALHPTSVHALRPADIQVVAALGDSLTAGNGIGSKPDDLPDVTTQYRGLSYSAGGDGSLENVTTLPSSILREFNRNLTGYAVGTGDANDTNAFLNQAVPGAKARDLMSQVQTLMQKMKDDHRVNFHEDWKVITVLIGGSDLCDYCTDSNLYDAANFVHHLRNALDVLHREVPRVLVNLVDFLNPTIMRQVFLGNPDKCPVQQASVLCNCVLTLRENSQELARLEAFSRAYQSSMRELVGSGRYDTQEDFSVVLQPFFQNIQLPVLQDGLPDTSFFAPDCIHPNQKFHSQLARALWTNMLEPLGSKTETLDLRAEMPITCPTQNEPFLRTPRNSNYTYPIKPAIENWGSDFLCTEWKASNSVPTSVHQLRPADIKVVAALGDSLTTAVGARPNNSSDLPTSWRGLSWSIGGDGNLETHTTLPSILKKFNPYLLGFSTSTWEGTAGLNVAAEGARARRDMPAQAWDLVERMKNSPIHFQEDWKIITLFIGGNDLCDFCNDLVGEYVQHIQQALDILSEELPRAFVNVVEVMELASLYQGQGGKCAMLAAQNNCTCLRHSQSSLEKQELKKVNWNLQHGISSFSYWHQYTQREDFAVVVQPFFQNTLTPLNRGDTDLTFFSEDCFHFSDRGHAEMAIALWNNMLEPVGRKTTSNNFTHSRAKLKCPSPVSPYLYTLRNSRLLPDQAEEAPEVLYWAVPVAAGVGLVVGIIGTVVWRCRRGGRREDPPMSLRTVALSEQ ID NO:831624 bpNOV24b,GCCGGCTGACATCAATGTAATTGGAGCCCTGGGTGACTCTCTCACGGCAGGCAATGGGCG57399-02 DNA SequenceGCCGGGTCCACACCTGGGAACGTCTTGGACGTCTTGACTCAGTACCGAGGCCTGTCCTGGAGCGTCGGCGGAGATGAGAACATCGGCACCGTTACCACCCTGGCGAACATCCTCCGGGAATTCAACCCTTCCCTGAAGGGCTTCTCTGTTGGCACTGGGAAAGAAACCAGTCCTAATGCCTTCTTAAACCAGGCTGTGGCAGGAGGCCGAGCTGAGGATCTACCTGTCCAGGCCAGGAGGCTGGTGGACCTGATGAAGAATGACACGAGGATACACTTTCAGGAAGACTGGAAGATAATAACCCTGTTTATAGGCGGCAATGACCTCTGTGATTTCTGCAATGATCTGGTCCACTATTCCCCCCAGAACTTCACAGACAACATTGGAAAGGCCCTGGACATCCTCCATGCTGAGGTTCCTCGGGCATTTGTGAACCTGGTGACGGTGCTTGAGATCGTCAACCTGAGGGAGCTGTACCAGGAGAAAAAAGTCTACTGCCCAAGGATGATCCTCAGGTCTCTGTGTCCCTGTGTCCTGAAGTTTGATGATAACTCAACAGAACTTGCTACCCTCATCGAATTCAACAAGAAGTTTCAGGAGAAGACCCACCAACTGATTGAGAGTGGGCGATATGACACAAGGGAAGATTTTACTGTGGTTGTGCAGCCGTTCTTTGAAAACGTGGACATGCCAAAGACCTCGGAAGGATTGCCTGACAACTCTTTCTTCGCTCCTGACTGTTTCCACTTCAGCAGCAAGTCTCACTCCCGAGCAGCCAGTGCTCTCTGGAACAATATGCTGGAGCCTGTTGGCCAGAAGACGACTCGTCATAAGTTTGAAAACAAGATCAATATCACATGTCCGAACCAGGTCCAGCCGTTTCTGAGGACCTACAAGAACAGCATGCAGGGTCATGGGACCTGGCTGCCATGCAGGGACAGAGCCCCTTCTGCCTTGCACCCTACCTCAGTGCATGCCCTGAGACCTGCAGACATCCAAGTTGTGGCTGCTCTGGGGGATTCTCTGACCGCTGGCAATGGAATTGGCTCCAAACCAGACGACCTCCCCGATGTCACCACACAGTATCGGGGACTGTCATACAGAGAAAGTAAACCAGGGTTCTTATCAGACTCCTGGGTCAGCAAATCCAACAGGAAATGCACCAGAAAAGCACCAAATCCCTGAATCTTCACCTCCCCGCTTGCATGTATACGTGTACACGTGGTGTTCCTACGTCTCTGTTTACTGTCTTTATGTGTTTATTCATGTTGTCTTGTAGTCACACAGCTGCCTTTACATATATGTACACATCTGCACAGAAAACCTCTGAAACCCATCGCACACTTCGAGAGGCCATAACCAAGACACAATCACAATCAGCCATGTCTTGAAAGATTAGCAATTCGACAAGAGGAAAGGGTGAGAAAGGGCATCCCGAACACGGAAGTGGAGAAGCTCAGGGTGTGTCAGGCGAGCGGTTGCGTGTAGATATTCTCAAGTTTCTTTCTCTCCTAATAAAGTTCTCATTCCTGTAGGCTTCAAAGTAAGTGGCGAGTAGCTCAGAATORF Start: ATG at 311ORF Stop: TGA at 1241SEQ ID NO:84310 aaMW at 35240.6 kDNOV24b,MKNDTRIHFQEDWKIITLFIGGNDLCHFCNDLVHYSPQNFTDNIGKALDILHAEVPRACG57399-02 ProteinSequenceFVNLVTVLEIVNLRELYQEKKVYCPRMILRSLCPCVLKFDDNSTELATLIEFNKKFQEKTHQLIESGRYDTREDPTVVVQPFFENVDMPKTSEGLPDNSFFAPDCFHFSSKSHSRAASALWNNMLEPVGQKTTRHKFENKINITCPNQVQPFLRTYKNSMQGHGTWLPCRDRAPSALHPTSVHALRPADIQVVAALGDSLTAGNGIGSKPDDLPDVTTQYRGLSYRESKPGFLSDSWVSKSNRKCTRKAPNPSEQ ID NO:854425 bpNOV24c,CTGGAGCATTCTGGCATGGGGCTGCGGCCAGGCATTTTCCTCCTGGAGCTGCTGCTGCCG57399-03 DNA SequenceTTCTGGGGCAAGGTACCCCTCAGATCCATACCTCTCCTAGAAAGAGTACATTGGAAGGGCAGCTATGGCCAGAGACAGTTCACTCTCTGAAGCCTTCTGATATTAAATTTGTGGCAGCCATTGGCAATCTGGAAATTGTGCCAGACCCAGGGACGGGCGATCTGGAGAAGCAAGACGAAAGGCCACAGCAGGTGTGCATGGGAGTGATGACAGTCCTTTCAGACATCATCAGATATTTCAGTCCTTCTGTTCCAATGCCTGTGTGCCACACTGGAAAGAGAGTCATACCCCACGATGGTGCTGAGGACTTGTGGATTCAGGCTCAAGAACTGGTGAGAAACATGAAAGAGAACCAACTTGACTTTCAATTTGACTGGAAGCTCATCAATGTGTTCTTCAGTAATGCAAGCCAGTGTTACCTGTGCCCCTCTGCTCAACAGAATGCGCTTGCGGCGGGCGGCGTGGATGAGCTGATGGGGGTGCTGGACTACCTGCAGCAGGAGGTGCCCAGAGCATTTGTAAACCTGGTGGACCTCTCTGAGGTTGCAGAGGTCTCTCGTCAGTATCACGGCACTTGGCTCAGCCCTGCACCAGAGCCCTGTAATTGCTCAGAGGAGACCACCCGGCTGGCCAAGGTGGTGATGCAGTGGTCTTATCAGGAAGCCTGGAACAGCCTCCTGGCCTCCAGCAGGTACAGTGAGCAGGAGTCCTTCACCGTGGTTTTCCAGCCTTTCTTCTATGAGACCACCCCATCTGACCCCCGACTCCAGGATTCTACCACGCTGGCCTGGCATCTCTGGAATAGGATGATGGAGCCAGCAGGAGAGAAGATGAGCCATTGAGTGTAAAACACGGGAGGCCAAATGAAGTGTCCCTCTCAGGAGAGCCCCTATCTGTTCAGCTACAGAAACAGCAACTACCTGACCAGACTGCAGAAACCCCAAGACAAGCTTGAGGTAAGAGAAGGAGCGGAAATCAGATGTCCTGACAAAGACCCCTCCGATACGGTTCCCACCTCAGTTCATAGGCTGAAGCCGGCTGACATCAACGTAATTGGAGCCCTGGGTGACTCTCTCACGGCAGGCAATGGGGCCGGGTCCACACCTGGGAACCTCTTGGACGTCTTGACTCAGTACCGAGGCCTGTCCTGGAGCGTCGGCGGAGATGAGAACATCGGCACCGTTACCACCCTGGCGGACATCCTCCGGGAATTCAACCCTTCCCTGAAGGGCTTCTCTGTTGGCACTGGGAAAGAAACCAGTCCTAATGCCTTCTTAAACCAGGCTGTGGCAGGAGGCCGAGCTGAGCAGGCCAGGAGGCTGGTGGACCTGATGAAGAATGACACGAGGATACACTTTCAGGAAGACTCCAACATAATAACCCTGTTTATAGGCGGCAATGACCTCTGTGATTTCTGCAATGATCTGGTACACTATTCTCCCCAGAACTTCACAGACAACATTGGAAAGGCCCTGGACATCCTCCATGCTGAGGTTCCTCGGGCATTTGTGAACCTGGTGACGGTGCTTGAGATCGTCAACCTGAGGGAGCTGTACCAGGACAAAAAAGTCTACTGCCCAAGGATGATCCTCAGGTCACTGTGTCCCTGTGTCCTGAAGTTTGATGATAACTCAACAGAACTTGCTACCCTCATCGAATTCAACAACAAGTTTCAGGAGAAGACCCACCAACTGATTGAGAGTGGGCGATATGACACAAGGGAAGATTTTACTGTGGTTGTGCAGCCGTTCTTTGAAAACGTGCACATGCCAAAGACCCAGGAAGGATTGCCTGACAACTCTTTCTTCGCTCCTGACTGTTTCCACTTCAGCAGCAAGTCTCACTCCCGAGCAGCCAGTGCTCTCTGGAACAATATGCTGGAGCCTGTTOCCCAGAAGACGACTCGTCATAAGTTTGAAAACAAGATCAATATCACATGTCCGAACCACGTAGAGTGGCCGTTTCTGAGGACCTACAAGAACAGCATGCAGGGTCATGGGACCTGGCTGCCATGCAGGGACAGAGCCCCTTCTGCCTTGCACCCTACCTCAGTCCATGCCCTGAGACCTGCAGACATCCAAGTTGTGGCTGCTCTGGGGGATTCTCTGACCGCTGGCAATGGAATTGGCTCCAAACCAGACGACCTCCCCGATGTCACCACACAGTATCGGGGACTGTCATACAGTGCAGGAGGGGACGGCTCCCTGGAGAATGTGACCACCTTACCTGATATCCTTCGGGAGTTTAACAGAAACCTCACAGGCTACGCCGTGGGCACGGGTGATCCCAATGACACGAATGCATTCCTCAATCAAGCTGTTCCCGGAGCAAAGGCTAGGGATCTTATGAGCCAAGTCCAAACTCTGATGCACAAGATGAAAGATGATCATAGAGTAAATTTCCATGAAGACTGGAAGGTCATCACAGTGCTGATCGGAGGCAGCGATTTATGTGACTACTGCACAGATTCGAATCTGTATTCTGCAGCCAACTTTGTTCACCATCTCCGCAATGCCTTGGACGTCCTGCATAGAGAGGTGCCCAGAGTCCTGGTCAACCTCGTCGACTTCCTGAACCCCACTATCATGCGGCAGGTGTTCCTGGGAAACCCAGACAAGTGCCCAGTGCAGCAGGCCAGCGTTTTGTGTAACTGCGTTCTGACCCTGCGGGAGAACTCCCAAGAGCTAGCCAGGCTGGAGGCCTTCAGCCGACCCTACCAGAGCAGCATGCGCGAGCTGGTGGGGTCAGGCCGCTATGACACGCAGGAGGACTTCTCTGTGGTGCTGCAGCCCTTCTTCCAGAACATCCAGCTCCCTGTCCTGCAGGATGGGCTCCCAGATACGTCCTTCTTTGCCCCAGACTGCATCCACCCAAATCAGAAATTCCACTCCCAGCTGGCCAGAGCCCTTTGGACCAATATGCTTGAACCACTTGGAAGCAAAACAGAGACCCTGGACCTGAGAGCAGAGATGCCCATCACCTGTCCCACTCAGAATGAGCCCTTCCTGAGAACCCCTCGGAATAGTAACTACACGTACCCCATCAAGCCAGCCATTGAGAACTGGGGCAGTGACTTCCTGTGTACAGAGTGGAAGGCTTCCAATAGTGTTCCAACCTCTGTCCACCAGCTCCCACCAGCAGACATCAAAGTGGTGGCCGCCCTGGGTGACTCTCTGACTGTGGCAGTGGGAGCTCGACCAAACAACTCCAGTGACCTACCCACATCTTGGAGGGGACTCTCTTGGAGCATTGGAGGGGATGGGAACTTGGAGACTCACACCACACTGCCCGACATTCTGAAGAAGTTCAACCCTTACCTCCTTGGCTTCTCTACCAGCACCTGGGAGGGGACAGCAGGACTAAATGTGGCAGCGGAAGGGGCCAGAGCTAGGGACATGCCAGCCCAGGCCTGGGACCTGGTAGAGCGAATGAAAAACAGCCCCCAGGACATCAACCTGGAGAAAGACTGGAAGCTGGTCACACTCTTCATTGGGGTCAACGACTTGTGTCATTACTGTGAGAATCCGGTAGGCGAATATGTTCAGCACATCCAACAGGCCCTGGACATCCTCTCTGAGGAGCTCCCAAGGGCTTTCGTCAACGTGGTGGAGGTCATGGAGCTGGCTAGCCTGTACCAGGGCCAAGGCGGGAAATGTGCCATGCTGGCAGCTCAGAACAACTGCACTTGCCTCAGACACTCGCAAAGCTCCCTGGAGAAGCAAGAACTGAAGAAAGTGAACTGGAACCTCCAGCATGGCATCTCCAGTTTCTCCTACTGGCACCAATACACACAGCGTGAGGACTTTGCGGTTGTGGTGCAGCCTTTCTTCCAAAACACACTCACCCCACTGAACAGAGGGGACACTGACCTCACCTTCTTCTCCGAGGACTGTTTTCACTTCTCAGACCGCGGGCATGCCGAGATGGCCATCGCACTCTGGAACAACATGCTGGAACCAGTGGGCCGCAAGACTACCTCCAACAACTTCACCCACAGCCGAGCCAAACTCAAGTGCCCCTCTCCTGAGAGCCCTTACCTCTACACCCTGCGGAACAGCCGATTGCTCCCAGACCAGGCTGAAGAAGCCCCCGAGGTGCTCTACTGGGCTGTCCCAGTGGCAGCGGGAGTCGGCCTTGTGGTGGGCATCATCGGGACAGTGGTCTGGAGGTGCAGGAGAGGTGGCCGGAGGGAAGATCCTCCAATGAGCCTGCGCACTGTGGCCCTCTAGGCCCGGGGGTGGGTCCTCACCCTAAACTCCCTATAGCCACTCTCTTCACCGCCCTCTGCCCCAGCCACTCCCGGCCACCAGGACATGCTTCAATGCCTGGTGCCATAGGAAGCCCAGGGGACAGTCACAACTTCTTGGORF Start ATG at 16ORF Stop: TAG at 4285SEQ ID NO:861423 aaMW at 159352.7 kDNOV24c,MGLRPGIFLLELLLLLGQGTPQIHTSPRKSTLEGQLWPETVHSLKPSKIKFVAAIGNLCG57399-03 ProteinSequenceEIVPDPGTGDLEKQDERPQQVCMGVMTVLSDIIRYFSPSVPMPVCHTGKRVIPHDGAEDLWIQAQELVRNMKENQLDFQFDWKLINVFFSNASQCYLCPSAQQNGLAAGGVDELMGVLDYLQQEVPRAFVNLVDLSEVAEVSRQYHGTWLSPAPEPCNCSEETTRLAKVVMQWSYQEAWNSLLASSRYSEQESFTVVFQPFFYETTPSDPRLQDSTTLAWHLWNRMMEPAGEKDEPLSVKHGRPMKCPSQESPYLFSYRNSNYLTRLQKPQDKLEVREGAEIRCPDKDPSDTVPTSVHRLKPADINVIGALGDSLTAGNGAGSTPGNVLDVLTQYRGLSWSVGGDENIGTVTTLADILREFNPSLKGFSVGTGKETSPNAFLNQAVAGGRAEQARRLVDLMKNDTRIHFQEDWKIITLFIGGNDLCDFCNDLVHYSPQNFTDNIGKALDILHAEVPRAFVNIVTVLEIVNLRELYQEKKVYCPRMILRSLCPCVLKFDDNSTELATLIEFWKKFQEKTHQLIESGRYDTREDFTVVVQPFFENVDMPKTQEGLPDNSFFAPDCFHFSSKSHSRAASALWNNMLEPVGQKTTRHKFENKINITCPNQVEWPFLRTYKNSMQGHGTWLPCRDRAPSAIHPTSVHALRPADIQVVAALGDSLTAGNGIGSKPDDLPDVTTQYRGLSYSAGGDGSLENVTTLPDILREFNRNLTGYAVGTGDANDTNAFLNQAVPGAKARDLMSQVQTLMQKMKDDHRVNFHEDWKVITVLIGGSDLCDYCTDSNLYSAANFVHHLRNALDVLHREVPRVLVNLVDFLNPTIMRQVFLGNPDKCPVQQASVLCNCVLTLRENSQELARLEAFSRAYQSSMRELVGSGRYDTQEDFSVVLQPFFQNIQLPVLQDGLPDTSFFAPDCIHPNQKFHSQLARALWTNNLEPLGSKTETLDLRAEMPITCPTQNEPFLRTPRNSNYTYPIKPAIENWGSDFLCTEWKASNSVPTSVHQLRPADIKVVAALGDSLTVAVGARPNNSSDLPTSWRGLSWSIGGDGNLETHTTLPDILKKPNPYLLGPSTSTWEGTAGLNVAAEGARARDMPAQAWDLVERMKNSPQDINLEKDWKLVTLFIGVNDLCHYCENPVGEYVQHIQQALDILSEELPRAFVNVVEVMELASLYQGQGGKCAMLAAQNNCTCLRHSQSSLEKQELKKVNWNLQHGISSFSYWHQYTQREDFAVVVQPFFQNTLTPLNRGDTDLTFFSEDCFHFSDRGHAEMAIALWNNMLEPVGRKTTSNNFTHSRAKLKCPSPESPYLYTLRNSRLLPDQAEEAPEVLYWAVPVAAGVGLVVGIIGTVVWRCRRGGRREDPPMSLRTVAL


[0449] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 24B.
126TABLE 24BComparison of NOV24a against NOV24b through NOV24c.ProteinNOV24a Residues/Identities/SimilaritiesSequenceMatch Residuesfor the Matched RegionNOV24b454 . . . 748 283/295 (95%) 1 . . . 293 285/295 (95%)NOV24c 27 . . . 14191211/1426 (84%) 23 . . . 14231261/1426 (87%)


[0450] Further analysis of the NOV24a protein yielded the following properties shown in Table 24C.
127TABLE 24CProtein Sequence Properties NOV24aPSort0.6850 probability located in endoplasmic reticulumanalysis:(membrane); 0.6400 probability located in plasma membrane;0.4600 probability located in Golgi body; 0.1080 probabilitylocated in nucleusSignalPLikely cleavage site between residues 24 and 25analysis:


[0451] A search of the NOV24a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 24D.
128TABLE 24DGeneseq Results for NOV24aIdentities/NOV24aSimilaritiesProtein/Residues/for theGeneseqOrganism/LengthMatchMatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAW30751Rat phospho- 50 . . . 1403 911/14040.0lipase-B/lipase—(64%)Rattus rattus 60 . . . 14471077/14041450 aa.(75%)[JP09248190-A,Sep. 22, 1997]ABB11053Human phospho-985 . . . 1203205/224 e−117lipase B Homo(91%)sapiens, 267 aa.45 . . . 267213/224[WO200157188-(94%)A2, Aug. 9,2001]AAM25824Human protein985 . . . 1203205/224 e−117sequence SEQ ID(91%)NO:1339—Homo45 . . . 267213/224sapiens, 267 aa.(94%)[WO200153455-A2, Jul. 26, 2001]AAM95420Human979 . . . 1106110/1303e−56 reproductive(84%)system related 4 . . . 133117/130antigen SEQ ID(89%)NO:4078—Homosapiens, 148 aa.[WO200155320-A2, Aug. 2,2001]ABB11237Human phospho-393 . . . 478 84/903e−40 lipase homologue,(93%)SEQ ID NO:43 . . . 13286/901607—Homo(95%)sapiens, 132 aa.[WO200157188-A2, Aug. 9,2001]


[0452] In a BLAST search of public sequence databases, the NOV24a protein was found to have homology to the proteins shown in the BLASTP data in Table 24E.
129TABLE 24EPublic BLASTP Results for NOV24aNOV24aIdentities/ProteinResidues/Similarities forAccessionProtein/Matchthe MatchedExpectNumberOrganism/LengthResiduesPortionValueQ05017Phospholipase 6 . . . 14161042/14660.0ADRAB-B(71%)precursor 2 . . . 14561179/1466(EC 3.1.-.-)—(80%)Oryctolaguscuniculus(Rabbit), 1458 aa.O70320PHOSPHO- 7 . . . 1414 965/14740.0LIPASE B—(65%)Cavia porcellus 3 . . . 14581135/1474(Guinea pig),(76%)1463 aa.O54728PHOSPHO- 50 . . . 1403 911/14040.0LIPASE B—(64%)Rattus norvegicus 60 . . . 14471077/1404(Rat), 1450 aa.(75%)Q96DP9CDNA FLJ30866454 . . . 714 257/261 e−151FIS, CLONE(98%)FEBRA2004110, 1 . . . 259258/261HIGHLY(98%)SIMILAR TOPHOSPHO-LIPASEADRAB-BPRECURSOR(EC 3.1.-.-)—Homo sapiens(Human), 270 aa.Q9N2Z4HYPO-343 . . . 673 130/3431e−59 THETICAL(37%)41.4 KDA37 . . . 369202/343PROTEIN—(57%)Caenorhabditiselegans, 377 aa.


[0453] PFam analysis predicts that the NOV24a protein contains the domains shown in the Table 24F.
130TABLE 24FDomain Analysis of NOV24aIdentities/NOV24aSimilarities forExpectPfam DomainMatch Regionthe Matched RegionValueLipase_GDSL: domain360 . . . 484 54/147 (37%)4.8e−421 of 3116/147 (79%)Lipase_GDSL: domain705 . . . 834 57/147 (39%)4.5e−442 of 3116/147 (79%)SecA_protein: domain834 . . . 851 10/20 (50%)4.91 of 1 17/20 (85%)Vitellogenin_N: domain1107 . . . 1124  8/18 (44%)3.81 of 1 17/18 (94%)Lipase_GDSL: domain1062 . . . 1185 48/147 (33%)6.3e−373 of 3114/147 (78%)



Example 25

[0454] The NOV25 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 25A.
131TABLE 25ANOV25 Sequence AnalysisSEQ ID NO:871348 bpNOV25a,CTGGGTCGCCCCTGTTCTACCCAGATTGGGATGGCAGCGACGCTGATCCTGGAGCCCGCG59311-01 DNA SequenceCGGGCCGCTGCTGCTGGGACGAGCCGCTGCGCATCGCAGTGCGCGGCCTGGCCCCGGAGCAGCCAGTCACGCTGCGCACGTCCCTGCGCGACGAAGAGGGCGCGCTCTTCCGGGCCCACGCGCGCTACCGTGCCGACGCCCGCGACGAGCTGGACCTGGAGCGCGCGCCCGCGCTGGGAGGCAGCTTCGCGGGGCTCCAGCCCATGGGGCTGCTGTGGGCGTTGGAGCCCGAGAAAGCCTTGGTGCGGCTGGTGAAGCGCGACGTGCGGACGCCCTTCGCCGTGGAGCTGGAAGTGCTGGACGGCCACGACACCGAGCCCGGGCGGCTGCTGTGCCTGGCGCAGAACAAGCGCGACTTTCTCCGGCCGGGGGTGCGGCGCGAGCCGGTGCGCGCGGGCCCGGTGCGCGCCGCGCTCTTCCTGCCGCCGGATAGGGGGCCCTTTCCTGGGATCATTGATCTGTTTGGGAGCAGCAGGGGCCTTTGTGAATACAGGGCCAGCCTCCTGGCCGGACATGGTTTTGCTGTGCTTGCCCTGGCTTATTTCAGATTTGAAGACCTCCCCGAAGATCTGAATGATGTACATCTGGAGTACTTTGAAGAAGCCGTGGACTTTATGCTGCAGCATCCAAAGGTGAAAGGTCCTAGTATTGCGCTTCTTGGATTTTCCAAAGGAGGTGACCTGTGTCTCTCAATGGCTTCTTTCTTGAAGGGCATCACAGCCACTGTACTTATCAATGCCTGTGTAGCCAACACAGTAGCTCCTCTACATTACAAGGATATGATTATTCCTAAACTTGTCGATGATCTAGGAAAAGTAAAAATCACTAAGTCAGGATTTCTCACTTTTATGGACACTTGGAGCAATCCACTGGAGGAACACAATCACCAAAGTCTTGTTCCATTGGAAAAGGCGCAGGTGCCCTTCTTGTTTATTGTTGGCATGGATGATCAAAGCTGGAAGAGTGAATTCTATGCTCAGATAGCCTCTGAAAGGCTACAAGCTCATGGGAAAGAAAGACCCCAGATAATCTGTTACCCAGAAACTGGTCACTGTATTGACCCACCTTATTTTCCTCCTTCTAGAGCTTCTGTGCACGCTGTTTTGGGTGAGGCAATATTCTATGGAGGTGAGCCAAAGGCTCACTCAAAGGCACAGGTAGATGCCTGGCAGCAAATTCAAACTTTCTTCCATAAACATCTCAATGGTAAAAAATCTGTCAAGCACAGCAAAATATAACATTGTAGCCACAGACCAGATACCATTAATAAAAATCCTATTCATACAACTTORF Start: ATG at 31ORF Stop: TAA at 1294SEQ ID NO:88421 aaMW at 46815.4 kDNOV25a,MAATLILEPAGRCCWDEPLRIAVRGLAPEQPVTLRTSLRDEEGALFRAHARYRADARDCG59311-01 Protein SequnceELDLERAPALGGSFAGLQPMGLLWALEPEKALVRLVKRDVRTPFAVELEVLDGHDTEPGRLLCLAQNKRDFLRPGVRREPVRAGPVRAALFLPPDRGPFPFIIDLFGSSRGLCEYRASLLAGHGFAVLALAYFRFEDLPEDLNDVHLEYFEEAVDFMLQHPKVKGPSIALLGFSKGGDLCLSMASFLKGITATVLINACVANTVAPLHYKDMIIPKLVDDLGKVKITKSGFLTFMDTWSNPLEEHNHQSLVPLEKAQVPFLFIVGMDDQSWKSEFYAQIASERLQAHGKERPQIICYPETGHCIDPPYFPPSRASVHAVLGEAIFYGGEPKAHSKAQVDAWQQIQTFFHKHLNGKKSVKHSKISEQ ID NO:891021 bpNOV25b,AGATTGGGATGGCAGCGACGCTGATCCTGGAGCCCGCGGGCCGCTGCTGCTGGGACGACG59311-01 DNA SequenceGCCGCTGCGCATCGCAGTGCGCGGCCTGGCCCCGGAGCAGCCAGTCACGCTGCGCACGTCCCTGCGCGACGAAGAGGGCGCGCTCTTCCGGGCCCACGCGCGCTACCGTGCCGACGCCTCTAATCCCGGCACTTTGGGGGGCCAAGGCAGGGGGCCCTTTCCTGGGATCATTGATCTGTTTGGGAGCAGCAGGGGCCTTTGTGAATACAGGGCCAGCCTCCTGGCCGGACATGGTTTTGCTGTGCTTGCCCTGGCTTATTTCAGATTTGAAGACCTCCCCGAAGATCTGAATGATGTACATCTGGAGTACTTTGAAGAAGCCGTGGACTTTATGCTGCAGCATCCAAAGGTGAAAGGTCCTAGTATTGCGCTTCTTGGATTTTCCAAAGGAGGTGACCTGTGTCTCTCAATGGCTTCTTTCTTGAAGGGCATCACAGCCACTGTACTTATCAATGCCTGTGTAGCCAACACAGTAGCTCCTCTACATTACAAGGATATGATTATTCCTAAACTTGTCGATGATCTAGGAAAAGTAAAAATCACTAAGTCAGGATTTCTCACTTTTATGGACACTTGGAGCAATCCACTGGAGGAACACAATCACCAAAGTCTTGTTCCATTGGAAAAGGCGCAGGTGCCCTTCTTGTTTATTGTTGGCATGGATGATCAAAGCTGGAAGAGTGAATTCTATGCTCAGATAGCCTCTGAAAGGCTACAAGCTCATGGGAAAGAAAGACCCCAGATAATCTGTTACCCAGAAACTGGTCACTGTATTGACCCACCTTATTTTCCTCCTTCTAGAGCTTCTGTGCACGCTGTTTTGGGTGAGGCAATATTCTATGGAGGTGAGCCAAAGGCTCACTCAAAGGCACAGGTAGATGCCTGGCAGCAAATTCAAACTTTCTTCCATAAACATCTCAATGGTAAAAAATCTGTCAAGCACAGCAAAATATAACATTGTAGORF Start: ATG at 9ORF Stop: TAA at 1011SEQ ID NO:90334 aaMW at 36926.0 kDNOV25b,MAATLILEPAGRCCWDEPLRIAVRGLAPEQPVTLRTSLRDEEGALFRAHARYRADASNCG59311-02 Protein SequencePGTLGGQGRGPFPGIIDLFGSSRGLCEYRASLLAGHGFAVLALAYFRFEDLPEDLNDVHLEYFEEAVDFMLQHPKVKGPSIALLGFSKGGDLCLSMASFLKGITATVLINACVANTVAPLHYKDMIIPKLVDDLGKVKITKSGFLTFMDTWSNPLEEHNHQSLVPLEKAQVPFLFIVGMDDQSWKSEFYAQIASERLQAHGKERPQIICYPETGHCIDPPYFPPSRASVHAVLGEAIFYGGEPKAHSKAQVDAWQQIQTFFHKHLNGKKSVKHSKISEQ ID NO:911021 bpNOV25c,AGATTGGGATGGCAGCGACGCTGATCCTGGAGCCCGCGGGCCGCTGCTGCTGGGACGACG59311-03 DNA SequenceGCCGCTGCGCATCGCAGTGCGCGGCCTGGCCCCGGAGCAGCCAGTCACGCTGCGCACGTCCCTGCGCGACGAAGAGGGCGCGCTCTTCCGGGCCCACGCGCGCTACCGTGCCGACGCCTCTAATCCCGGCACTTTGGGAGGCCAAGGCAGGGGGCCCTTTCCTGGGATCATTGATCTGTTTGGGAGCAGCAGGGGCCTTTGTGAATACAGGGCCAGCCTCCTGGCCGGACATGGTTTTGCTGTGCTTGCCCTGGCTTATTTCAGATTTGAAGACCTCCCCGAAGATCTGAATGATGTACATCTGGAGTACTTTGAAGAAGCCGTGGACTTTATGCTGCAGCATCCAAAGGTGAAAGGTCCTAGTATTGCGCTTCTTGGATTTTCCAAAGGAGGTGACCTGTGTCTCTCAATGGCTTCTTTCTTGAAGGGCATCACAGCCACTGTACTTATCAATGCCTGTGTAGCCAACACAGTAGCTCCTCTACATTACAAGGATATGATTATTCCTAAACTTGTCGATGATCTAGGAAAAGTAAAAATCACTAAGTCAGGATTTCTCACTTTTATGGACACTTGGAGCAATCCACTGGAGGAACACAATCACCAAAGTCTTGTTCCATTGOAAAAGGCGCAGGTGCCCTTCTTGTTTATTGTTGGCATGGATGATCAAAGCTGGAAGAGTGAATTCTATGCTCAGATAGCCTCTGAAAGGCTACAAGCTCATGGGAAAGAAAGACCCCAGATAATCTGTTACCCAGAAACTGGTCACTGTATTGACCCACCTTATTTTCCTCCTTCTAGAGCTTCTGTGCACGCTGTTTTGGGTGAGGCAATATTCTATGGAGGTGAGCCAAAGGCTCACTCAAAGGCACAGGTAGATGCCTGGCAGCAAATTCAAACTTTCTTCCATAAACATCTCAATGGTAAAAAATCTGTCAAGCACAGCAAAATATAACATTGTAGORF Start: ATG at 9ORF Stop: TAA at 1011SEQ ID NO:92334 aaMW at 36926.0 kDNOV25c,MAATLILEPAGRCCWDEPLRIAVRGLAPEQPVTLRTSLRDEEGALFRAHARYRADASNCG59311-03 Protein SequencePGTLGGQGRGPFPGIIDLFGSSRGLCEYRASLLAGHGFAVLALAYFRFEDLPEDLNDVHLEYFEEAVDFMLQHPKVKGPSIALLGFSKGGDLCLSMASFLKGITATVLINACVANTVAPLHYKDMIIPKLVDDLGKVKITKSGFLTFMDTWSNPLEEHNHQSLVPLEKAQVPFLFIVGMDDQSWKSEFYAQIASERLQAHGKERPQIICYPETGHCIDPPYFPPSRASVHAVLGEAIFYGGEPKAHSKAQVDAWQQIQTFFHKHLNGKKSVKHSKI


[0455] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 25B.
132TABLE 25BComparison of NOV25a against NOV25b through NOV25c.ProteinNOV25a Residues/Identities/SimilaritiesSequenceMatch Residuesfor the Matched RegionNOV25b154 . . . 421268/268 (100%) 67 . . . 334268/268 (100%)NOV25c154 . . . 421268/268 (100%) 67 . . . 334268/268 (100%)


[0456] Further analysis of the NOV25a protein yielded the following properties shown in Table 25C.
133TABLE 25CProtein Sequence Properties NOV25aPSort0.4500 probability located in cytoplasm; 0.3630 probabilityanalysis:located in microbody (peroxisome); 0.1958 probability locatedin lysosome (lumen); 0.1000 probability located inmitochondrial matrix spaceSignalPNo Known Signal Sequence Predictedanalysis:


[0457] A search of the NOV25a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 25D.
134TABLE 25DGeneseq Results for NOV25aNOV25aIdentities/Protein/Residues/Similarities forGeneseqOrganism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAM41490Human poly- 1 . . . 421288/421e−175peptide SEQ ID(68%)NO 6421—Homo 74 . . . 494347/421sapiens, 494 aa.(82%)Jul. 26, 2001]AAM39704Human poly- 1 . . . 421288/421e−175peptide SEQ ID(68%)NO 2849—Homo 63 . . . 483346/421sapiens, 483 aa.(81%)[WO200153312-A1, Jul. 26, 2001]AAY71112Human Hydrolase 1 . . . 421288/421e−175protein-10(68%)(HYDRL-10)— 63 . . . 483346/421Homo sapiens,(81%)483 aa.[WO200028045-A2, May 18,2000]AAB93479Human protein 1 . . . 421287/421e−175sequence SEQ ID(68%)NO:12766— 63 . . . 483346/421Homo sapiens,(82%)483 aa.[EP1074617-A2,Feb. 7, 2001]AAY07932Human secreted241 . . . 421 181/181e−105protein fragment(100%)encoded from 1 . . . 181 181/181gene 81—Homo(100%)sapiens, 182 aa.[WO9918208-A1,Apr. 15, 1999]


[0458] In a BLAST search of public sequence databases, the NOV25a protein was found to have homology to the proteins shown in the BLASTP data in Table 25E.
135TABLE 25EPublic BLASTP Results for NOV25aNOV25aIdentities/ProteinResidues/Similarities forAccessionProtein/Matchthe MatchedExpectNumberOrganism/LengthResiduesPortionValueP49753Peroxisomal acyl- 1 . . . 421288/421 (68%)e−175coenzyme A 1 . . . 421347/421 (82%)thioester hydrolase2 (EC 3.1.2.2)(Peroxisomal long-chain acyl-coAthioesterase 2)(ZAP128)—Homosapiens (Human),421 aa.Q9QYR7Peroxisomal acyl- 1 . . . 421264/421 (62%)e−157coenzyme A12 . . . 432331/421 (77%)thioester hydrolase2 (EC 3.1.2.2)(Peroxisomal long-chain acyl-coAthioesterase 2)(PTE-Ia)—Musmusculus (Mouse),432 aa.O88267Cytosolic acyl 1 . . . 421268/421 (63%)e−153coenzyme A 1 . . . 419318/421 (74%)thioester hydrolase,inducible(EC 3.1.2.2) (Longchain acyl-CoAthioester hydrolase)(Long chain acyl-CoA hydrolase)(CTE-I) (LACH2)(ACH2) Rattusnorvegicus (Rat),419 aa.Q9QYR9Acyl coenzyme A 3 . . . 413264/411 (64%)e−153thioester hydrolase,44 . . . 452321/411 (77%)mitochondrialprecursor(EC 3.1.2.2) (Very-long-chain acyl-CoA thioesterase)(MTE-I)—Musmusculus (Mouse),453 aa.O55137Cytosolic acyl 1 . . . 413262/413 (63%)e−153coenzyme A 1 . . . 411319/413 (76%)thioester (Longchain acyl-CoAthioester hydrolase)(Long chain acyl-CoA hydrolase)(CTE-I)—Musmusculus (Mouse),419 aa.


[0459] PFam analysis predicts that the NOV25a protein contains the domains shown in the Table 25F.
136TABLE 25FDomain Analysis of NOV25aNOV25aIdentities/SimilaritiesExpectPfam DomainMatch Regionfor the Matched RegionValueNo Significant Matches Found



Example 26

[0460] The NOV26 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 26A.
137TABLE 26ANOV26 Sequence AnalysisSEQ ID NO:931375 bpNOV26a,GGGACGCCGGACGCCGTCCGGACATTCGGCGCGCTTGCCACGATCTTGGACGGGTCTCCG59309-01 DNA SequenceGGGCCTCGACCTTTGAATTCCCCGCTCCGGCTCCAAGATGTCAGCAACGCTGATCCTGGAGCCCCCAGGCCGCTGCTGCTGGAACGAGCCGGTGCGCATTGCCGTGCGCGGCCTGGCCCCGGAGCAGCGGGTTACGCTGCGCGCGTCCCTGCGCGACGAGAAGGGCGCGCTCTTCCGGGCCCACGCGCGCTACTGCGCCGACGCCCGCGGCGAGCTGGACCTGGAGCGCGCACCCGCGCTGGGCGGCAGCTTCGCGGGACTCGAGCCCATGGGGCTGCTCTGGGCCCTGGAACCCGAGAAGCCTTTTTGGCGCTTCCTGAAGCGGGACGTACAGATTCCTTTTGTCGTGGAGTTGGAGGTGCTGGACGGCCACGACCCCGAGCCTGGACGGCTGCTGTGCCAGGCGCAGCACGAGCGCCACTTCCTCCCGCCAGGGGTGCGGCGCCAGTCGGTGCGAGCGGGCCGGGTGCGCGCCACGCTCTTCCTGCCGCCAGGTGAGCCTGGACCCTTCCCAGGGATCATTGACATCTTTGGTATTGGAGGGGGCCTCTTGGAATATCGAGCCAGCCTCCTTGCTGGCCATGGCTTTGCCACGTTGGCTCTAGCTTATTATAACTTTGAAGATCTCCCCAATAACATGGACAACATATCCCTGGAGTACTTCGAAGAAGCCGTATGCTACATGCTTCAACATCCCCAGGTTAAAGGCCCAGGCATTGGGCTTTTGGGCATTTCTCTAGGAGCTGATATTTGTCTCTCAATGGCCTCATTCTTGAAGAATGTCTCAGCCACAGTTTCCATCAATGGATCTGGGATCAGTGGGAACACAGCCATCAACTATAAGCACAGTAGCATTCCACCATTGGGCTATGACCTGAGGAGAATCAAGGTAGCTTTCTCAGGCCTCGTGGACATTGTGGATATAAGGAATGCTCTCGTAGGAGGGTACAAGAACCCCAGCATGATTCCAATAGAGAAGGCCCAGGGGCCCATCCTGCTCATTGTTGGTCAGGATGACCATAACTGGAGAAGTGAGTTGTATGCCCAAACAGTCTCTGAACGGTTACAGGCCCATGGAAAGGAAAAACCCCAGATCATCTGTTACCCTGGGACTGGGCATTACATCGAGCCTCCTTACTTCCCCCTGTGCCCAGCTTCCCTTCACAGATTACTGAACAAACATGTTATATGGGGTGGGGAGCCCAGGGCTCATTCTAAGGCCCAGGAAGATGCCTGGAAGCAAATTCTAGCCTTCTTCTGCAAACACCTGGGAGGTACCCAGAAAACAGCTGTCCCTAAATTGTAATGCATTTGTCTORF Start: ATG at 96ORF Stop: TAA at 1362SEQ ID NO:94422 aaMW at 46455.1 kDNOV26a,MSATLILEPPGRCCWNEPVRIAVRGLAPEQRVTLRASLRDEKGALFRAHARYCADARGCG59309-01 Protein SequenceELDLERAPALGGSFAGLEPMGLLWALEPEKPFWRFLKRDVQIPFVVELEVLDGHDPEPGRLLCQAQHERHFLPPGVRRQSVRAGRVRATLFLPPGEPGPFPGIIDIFGIGGGLLEYRASLLAGHGFATLALAYYNFEDLPNNMDNISLEYFEEAVCYMLQHPQVKGPGIGLLGISLGADICLSMASFLKNVSATVSINGSGISGNTAINYKHSSIPPLGYDLRRIKVAFSGLVDIVDIRNALVGGYKNPSMIPIEKAQGPILLIVGQDDHNWRSELYAQTVSERLQAHGKEKPQIICYPGTGHYIEPPYFPLCPASLHRLLNKHVIWGGEPRAHSKAQEDAWKQILAFFCKHLGGTQKTAVPKL


[0461] Further analysis of the NOV26a protein yielded the following properties shown in Table 26B.
138TABLE 26BProtein Sequence Properties NOV26aPSort0.4500 probability located in cytoplasm; 0.2585 probabilityanalysis:located in lysosome (lumen); 0.1940 probability located inmicrobody (peroxisome); 0.1000 probability located inmitochondrial matrix spaceSignalPNo Known Signal Sequence Predictedanalysis:


[0462] A search of the NOV26a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 26C.
139TABLE 26CGeneseq Results for NOV26aNOV26aIdentities/Protein/Residues/Similarities forGeneseqOrganism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAM41490Human poly- 1 . . . 422296/422 (70%) e−179peptide SEQ ID 74 . . . 494341/422 (80%)NO 6421—Homosapiens, 494 aa.[WO200153312-A1, Jul. 26, 2001]AAM39704Human poly- 1 . . . 422296/422 (70%) e−179peptide SEQ ID 63 . . . 483341/422 (80%)NO 2849—Homosapiens, 483 aa.[WO200153312-A1, Jul. 26, 2001]AAY71112Human Hydrolase 1 . . . 422296/422 (70%) e−179protein-10 63 . . . 483341/422 (80%)(HYDRL-10)—Homo sapiens,483 aa.[WO200028045-A2, May 18,2000]AAB93479Human protein 1 . . . 422295/422 (69%) e−178sequence SEQ ID 63 . . . 483340/422 (79%)NO:12766—Homo sapiens,483 aa.[EP1074617-A2,Feb. 7, 2001]AAY07932Human secreted242 . . . 422 93/181 (51%)2e−48 protein fragment 1 . . . 181123/181 (67%)encoded fromgene 81—Homosapiens, 182 aa.[WO9918208-A1,Apr. 15, 1999]


[0463] In a BLAST search of public sequence databases, the NOV26a protein was found to have homology to the proteins shown in the BLASTP data in Table 26D.
140TABLE 26DPublic BLASTP Results for NOV26aNOV26aIdentities/ProteinResidues/Similarities forAccessionProtein/Matchthe MatchedExpectNumberOrganism/LengthResiduesPortionValueQ9QYR8PEROXISOMAL 1 . . . 422312/422 (73%)0.0LONG CHAIN 1 . . . 421362/422 (84%)ACYL-COA THIO-ESTERASE IB—Mus musculus(Mouse), 421 aa.P49753Peroxisomal acyl- 1 . . . 422296/422 (70%)e−178coenzyme A 1 . . . 421341/422 (80%)thioester hydrolase2 (EC 3.1.2.2)(Peroxisomal long-chain acyl-coAthioesterase 2)(ZAP128)—Homosapiens (Human),421 aa.Q9QYR7Peroxisomal acyl- 1 . . . 422281/424 (66%)e−163coenzyme A12 . . . 432333/424 (78%)thioester hydrolase2 (EC 3.1.2.2)(Peroxisomal long-chain acyl-coAthioesterase 2)(PTE-Ia)—Musmusculus (Mouse),432 aa.O55137Cytosolic acyl 1 . . . 422275/423 (65%)e−162coenzyme A 1 . . . 419330/423 (78%)thioester hydrolase,inducible(EC 3.1.2.2) (Longchain acyl-CoAthioester hydrolase)(Long chain acyl-CoA hydrolase)(CTE-I)—Musmusculus (Mouse),419 aa.O88267Cytosolic acyl 1 . . . 422276/423 (65%)e−162coenzyme A 1 . . . 419329/423 (77%)thioester hydrolase,inducible(EC 3.1.2.2) (Longchain acyl-CoAthioester hydrolase)(Long chain acyl-CoA hydrolase)(CTE-I) (LACH2)(ACH2) Rattusnorvegicus (Rat),419 aa.


[0464] PFam analysis predicts that the NOV26a protein contains the domains shown in the Table 26E.
141TABLE 26EDomain Analysis of NOV26aIdentities/NOV26aSimilaritiesMatchfor thePfam DomainRegionMatched RegionExpect ValueDLH: domain 1 of 2144 . . . 18817/52 (33%)6332/52 (62%)DLH: domain 2 of 2394 . . . 411 9/18 (50%)2.613/18 (72%)



Example 27

[0465] The NOV27 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 27A.
142TABLE 27ANOV27 Sequence AnalysisSEQ ID NO:951333 bpNOV27a,CCTGGCCCCCAAGCTCCCCACTCTGGTGCCCCGAGCAGCCCTGTGGGCAAGCAGCCGCCG57364-01 DNA SequenceCGCCATGGCCGAGCACCTGGAGCTGCTGGCAGAGATGCCCATGGTGGGCAGGATGAGCACACAGGAGCGGCTGAAGCATGCCCAGAAGCGGCGCGCCCAGCAGGTGAAGATGTGGGCCCAGGCTGAGAAGGAGGCCCAGGGCAAGAAGGGTCCTGGGGAGCGTCCCCGGAAGGAGGCAGCCAGCCAAGGGCTCCTGAAGCAGGTCCTCTTCCCTCCCAGTGTTGTCCTTCTGGAGGCCGCTGCCCGAAATGACCTGGAAGAAGTCCGCCAGTTCCTTGGGAGTGGGGTCAGCCCTGACTTGGCCAACGAGGACGGCCTGACGGCCCTGCACCAGTGCTGCATTGATGATTTCCGAGAGATGGTGCAGCAGCTCCTGGAGGCTGGGGCCAACATCAATGCCTGTGACAGTGAGTGCTGGACGCCTCTGCATGCTGCGGCCACCTGCGGCCACCTGCACCTGGTGGAGCTGCTCATCGCCAGTGGCGCCAATCTCCTGGCGGTCAACACCGACGGGAACATGCCCTATGACCTGTGTGATGATGAGCAGACGCTGGACTGCCTGGAGACTGCCATGGCCGACCGTGGCATCACCCAGGACAGCATCGAGGCCGCCCGGGCCGTGCCAGAACTGCGCATGCTGGACGACATCCGGAGCCGGCTGCAGGCCGGGGCAGACCTCCATGCCCCCCTGGACCACGGGGCCACGCTGCTGCACGTCGCAGCCGCCAACGGGTTCAGCGAGGCGGCTGCCCTGCTGCTGGAACACCGAGCCAGCCTGAGCGCTAAGGACCAAGACGGCTGGGAGCCGCTGCACGCCGCGGCCTACTGGGGCCAGGTGCCCCTGGTGGAGCTGCTCGTGGCGCACGGGGCCGACCTGAACGCAAAGTCCCTGATGGACGAGACGCCCCTTGATGTGTGCGGGGACGAGGAGGTGCGGGCCAAGCTGCTGGAGCTGAAGCACAAGCACGACGCCCTCCTGCGCGCCCAGAGCCGCCAGCGCTCCTTGCTGCGCCGCCGCACCTCCAGCGCCGGCAGCCGCGGGAAGGTGGTGAGGCGGGATGAGCCTAACCCAGCGCAGCGGCTGACGCATGTCCCAGAAGCGGCGCGCCCAGCAGGTGAAGATGTGGGCCCAGGCTGAGAAGGAGGCCCAGGGCAAGAAGGGTCCTGGGGAGCGTCCCCGGAAGGAGGCAGCCAGCCAAGGGCTCCTGAAGCAGGTCCTCTTCCCTCCCAGTGTTGTCCTTCTGGAGGCCGCTGCCCGAAATGACCTGGAAGAAGORF Start: ATG at 63ORF Stop: TGA at 1194SEQ ID NO:96377 aaMW at 41019.9 kDNOV27a,MAEHLELLAEMPMVGRMSTQERLKHAQKRRAQQVKMWAQAEKEAQGKKGPGERPRKEACG57364-01 Protein SequenceASQGLLKQVLFPPSVVLLEAAARNDLEEVRQFLGSGVSPDLANEDGLTALHQCCIDDFREMVQQLLEAGANINACDSECWTPLHAAATCGHLHLVELLIASGANLLAVNTDGNMPYDLCDDEQTLDCLETAMADRGITQDSIEAARAVPELRMLDDIRSRLQAGADLHAPLDHGATLLHVAAANGFSEAAALLLEHRASLSAKDQDGWEPLHAAAYWGQVPLVELLVAHGADLNAKSLMDETPLDVCGDEEVRAKLLELKHKHDALLRAQSRQRSLLRRRTSSAGSRGKVVRRDEPNPAQRLTHVPEAARPAGEDVGPG


[0466] Further analysis of the NOV27a protein yielded the following properties shown in Table 27B.
143TABLE 27BProtein Sequence Properties NOV27aPSort0.3000 probability located in microbody (peroxisome); 0.3000analysis:probability located in nucleus; 0.1547 probability located inlysosome (lumen); 0.1000 probability located in mitochondrialmatrix spaceSignalPNo Known Signal Sequence Predictedanalysis:


[0467] A search of the NOV27a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 27C.
144TABLE 27CGeneseq Results for NOV27aIdentities/NOV27aSimilaritiesProtein/Residues/for theGeneseqOrganism/LengthMatchMatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAM40636Human polypeptide 89 . . . 351262/263 e−151SEQ ID NO 5567— (99%)Homo sapiens, 1 . . . 263263/263440 aa. (99%)[WO200153312-A1,Jul. 26, 2001]AAM38850Human polypeptide119 . . . 351233/233 e−132SEQ ID NO 1995—(100%)Homo sapiens, 1 . . . 233233/233410 aa.(100%)[WO200153312-A1,Jul. 26, 2001]AAM78864Human protein SEQ 1 . . . 351209/351 e−118ID NO 1526— (59%)Homo sapiens, 1 . . . 348265/351567 aa. (74%)[WO200157190-A2,Aug. 9, 2001]ABB11817Human KIAA0823 45 . . . 354173/3163e−94 protein homologue, (54%)SEQ ID NO: 3 . . . 318226/3162187—Homo (70%)sapiens, 536 aa.[WO200157188-A2,Aug. 9, 2001]AAM79848Human protein 45 . . . 354173/3163e−94 SEQ ID NO 3494— (54%)Homo sapiens, 3 . . . 318226/316536 aa. (70%)[WO200157190-A2,Aug. 9, 2001]


[0468] In a BLAST search of public sequence databases, the NOV27a protein was found to have homology to the proteins shown in the BLASTP data in Table 27D.
145TABLE 27DPublic BLASTP Results for NOV27aNOV27aIdentities/ProteinResidues/SimilaritiesAccessionProtein/Matchfor theExpectNumberOrganism/LengthResiduesMatched PortionValueQ96134UNKNOWN1 . . . 351351/351 (100%)0.0(PROTEIN FOR1 . . . 351351/351 (100%)MGC:14333)—Homo sapiens(Human), 528 aa.Q923M0MYOSIN1 . . . 351301/351 (85%) e−171PHOSPHATASE1 . . . 351320/351 (90%) TARGETINGSUBUNIT 3MYPT3—Musmusculus(Mouse), 524 aa(fragment).AAL62093PROTEIN PHOS-1 . . . 351210/351 (59%) e−118PHATASE 11 . . . 348266/351 (74%) REGULATORYSUBUNIT 16B—Mus musculus(Mouse), 568 aa.Q95N27CAAX BOX1 . . . 351210/351 (59%) e−118PROTEIN1 . . . 348266/351 (74%) TIMAP—Bostaurus (Bovine),568 aa.Q96T49CAAX BOX1 . . . 351209/351 (59%) e−117PROTEIN1 . . . 348265/351 (74%) TIMAP—Homosapiens (Human),567 aa.


[0469] PFam analysis predicts that the NOV27a protein contains the domains shown in the Table 27E.
146TABLE 27EDomain Analysis of NOV27aNOV27aIdentities/SimilaritiesExpectPfam DomainMatch Regionfor the Matched RegionValueank: domain 1 of 5 70 . . . 102 8/33 (24%)9920/33 (61%)ank: domain 2 of 5103 . . . 13516/33 (48%)7.1e−0826/33 (79%)ank: domain 3 of 5136 . . . 16815/33 (45%)2.9e−0726/33 (79%)ank: domain 4 of 5231 . . . 26316/33 (48%)  2e−0624/33 (73%)ank: domain 5 of 5264 . . . 29616/33 (48%)2.7e−0827/33 (82%)



Example 28

[0470] The NOV28 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 28A.
147TABLE 28ANOV28 Sequence AnalysisSEQ ID NO:971719 bpNOV28a,CGGGCACAGGCTCACCCTCGAGTGGCACAGGAATCCCAGGTAGATGACGGCGGCCGCGCG59348-01 DNA SequenceGCTGGTGCTGCAGGGTCGCCAGCTCCCGCGGCAGCGGCCGGCGCCCCGGGATCTGGGGGCGCACCCTCAGGGTCGCAGGGGGTGCTGATCGGGGACAGGCTGTACTCCGGGGTGCTCATCACCTTGGAGAACTGCCTCCTGCCTGACGACAAGCTCCGTTTCACGCCGTCCATGTCGAGCGGCCTCGACACCGACACAGAGACCGACCTCCGCGTGGTGGGCTGCGAGCTCATCCAGGCGGCCGGTATCCTGCTCCGCCTGCCGCAGGTGGCCATGGCTACCGGGCAGGTGTTGTTCCAGCGGTTCTTTTATACCAAGTCCTTCGTGAAGCACTCCATGGAGCATGTGTCAATGGCCTGTGTCCACCTGGCTTCCAAGATAGAAGAGGCCCCAAGACGCATACGGGACGTCATCAATGTGTTTCACCGCCTTCGACAGCTGAGAGACAAAAAGAAGCCCGTGCCTCTACTACTGGATCAAGATTATGTTAATTTAAAGAACCAAATTATAAAGGCGGAAAGACGAGTTCTCAAAGAGTTGGGTTTCTGCGTCCATGTGAAGCATCCTCATAAGATAATCGTTATGTACCTTCAGGTGTTAGAGTGTGAGCGTAACCAACACCTGGTCCAGACCTCATGGAATTACATGAACGACAGCCTTCGCACCGACGTCTTCGTGCGGTTCCAGCCAGAGAGCATCGCCTGTGCCTGCATTTATCTTGCTGCCCGGACGCTGGAGATCCCTTTGCCCAATCGTCCCCATTGGTTTCTTTTGTTTGGAGCAACTGAAGAAGAAATTCAGGAAATCTGCTTAAAGATCTTGCAGCTTTATGCTCGGAAAAAGGTTGATCTCACACACCTGGAGGGTGAAGTGGAAAAAAGAAAGCACGCTATCGAAGAGGCAAAGGCCCAAGCCCGGGGCCTGTTGCCTGGGGGCACACAGGTGCTGGATGGTACCTCGGGGTTCTCTCCTGCCCCCAAGCTGGTGGAATCCCCCAAAGAAGGTAAAGGGAGCAAGCCTTCCCCACTGTCTGTGAAGAACACCAAGAGGAGGCTGGAGGGCGCCAAGAAAGCCAAGGCGGACAGCCCCGTGAACGGCTTGCCAAAGGGGCGAGAGAGTCGGAGTCGGAGCCGGAGCCGTGAGCAGAGCTACTCGAGGTCCCCATCCCGATCAGCGTCTCCTAAGAGGAGGAAAAGTGACAGCGGCTCCACATCTGGTGGGTCCAAGTCGCAGAGCCGCTCCCGGAGCAGGAGTGACTCCCCACCGAGACAGGCCCCCCGCAGCGCTCCCTACAAAGGCTCTGAGATTCGGGGCTCCCGGAAGTCCAAGGACTGCAAGTACCCCCAGAAGCCACACAAGTCTCGGAGCCGGAGTTCTTCCCGTTCTCGAAGCAGGTCACGGGAGCGGGCGGATAATCCGGGAAAATACAAGAAGAAAAGTCATTACTACAGAGATCAGCGACGAGAGCGCTCGAGGTCGTATGAACGCACAGGCCGTCGCTATGAGCGGGACCACCCTGGGCACAGCAGGCATCGGAGGTGACACGTGCTTCAGACCGGTCTGGGGTGCGGCGCACACCTGGGCCCGTGCAGGGCTCAGCTCGGCAGCAGCTCTGAGGGCAGCTCAATGAAAAAGTGAATGCACACGCCCTTGTTGGCGTGORF Start: ATG at 44ORF Stop: TGA at 1598SEQ ID NO:98518 aaMW at 58034.5 kDNOV28a,MTAAAAGAAGSAAPAAAAGAPGSGGAPSGSQGVLIGDRLYSGVLITLENCLLPDDKLRCG59348-01 Protein SequenceFTPSMSSGLDTDTETDLRVVGCELIQAAGILLRLPQVAMATGQVLFQRFFYTKSFVKHSMEHVSMACVHLASKIEEAPRRIRDVINVFHRLRQLRDKKKPVPLLLDQDYVNLKNQIIKAERRVLKELGFCVHVKHPHKIIVMYLQVLECERNQHLVQTSWNYMNDSLRTDVFVRFQPESIACACIYLAARTLEIPLPNRPHWFLLFGATEEEIQEICLKILQLYARKKVDLTHLEGEVEKRKHAIEEAKAQARGLLPGGTQVLDGTSGFSPAPKLVESPKEGKGSKPSPLSVKNTKRRLEGAKKAKADSPVNGLPKGRESRSRSRSREQSYSRSPSRSASPKRRKSDSGSTSGGSKSQSRSRSRSDSPPRQAPRSAPYKGSEIRGSRKSKDCKYPQKPHKSRSRSSSRSRSRSRERADNPGKYKKKSHYYRDQRRERSRSYERTGRRYERDHPGHSRHRR


[0471] Further analysis of the NOV28a protein yielded the following properties shown in Table 28B.
148TABLE 28BProtein Sequence Properties NOV28aPsort0.5500 probability located in endoplasmic reticulumanalysis:(membrane); 0.2400 probability located in nucleus; 0.1900probability located in lysosome (lumen); 0.1000 probabilitylocated in endoplasmic reticulum (lumen)SignalPNo Known Signal Sequence Predictedanalysis:


[0472] A search of the NOV28a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 28C.
149TABLE 28CGeneseq Results for NOV28aNOV28aIdentities/Protein/Residues/Similarities forGeneseqOrganism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAM94028Human stomach221 . . . 518298/298e−172cancer expressed(100%)polypeptide SEQ 1 . . . 298298/298ID NO 126—(100%)Homo sapiens,298 aa.[WO200109317-A1, Feb. 8, 2001]AAG64403Human paneth221 . . . 518298/298e−172cell enhanced(100%)expression-like 1 . . . 298298/298protein—Homo(100%)sapiens, 298 aa.[WO200138372-A1, May 31,2001]AAB94641Human protein221 . . . 518298/298e−172sequence SEQ ID(100%)NO:15526— 1 . . . 298298/298Homo sapiens,(100%)298 aa.[EP1074617-A2,Feb. 7, 2001]AAM78533Human protein 2 . . . 518316/526e−168SEQ ID NO (60%)1195—Homo 8 . . . 526390/526sapiens, 526 aa. (74%)[WO200157190-A2, Aug. 9,2001]AAB94371Human protein 2 . . . 518316/526e−168sequence SEQ ID (60%)NO:14909— 8 . . . 526390/526Homo sapiens, (74%)526 aa.[EP1074617-A2,Feb. 7, 2001]


[0473] In a BLAST search of public sequence databases, the NOV28a protein was found to have homology to the proteins shown in the BLASTP data in Table 28D.
150TABLE 28DPublic BLASTP Results for NOV28aNOV28aIdentities/ProteinResidues/SimilaritiesAccessionProtein/Matchfor theExpectNumberOrganism/LengthResiduesMatched PortionValueQ96S94HYPO- 3 . . . 518516/516 (100%)0.0THETICAL 5 . . . 520516/516 (100%)58.1 KDAPROTEIN—Homo sapiens(Human), 520 aa.Q9JJA7BRAIN CDNA, 1 . . . 518466/519 (89%) 0.0CLONE MNCB- 1 . . . 518482/519 (92%) 5160, SIMILARTO MUSMUSCULUSPANETH CELLENHANCEDEXPRESSIONPCEE MRNA—Mus musculus(Mouse), 518 aa.Q9UK58CYCLIN L 2 . . . 518316/526 (60%) e−167ANIA-6A— 8 . . . 526390/526 (74%) Homo sapiens(Human), 526 aa.Q9R1Q2CYCLIN ANIA- 2 . . . 518312/526 (59%) e−1656A—Rattus 9 . . . 527391/526 (74%) norvegicus(Rat), 527 aa.Q9WV44CYCLIN ANIA- 3 . . . 518314/526 (59%) e−1626A—Mus15 . . . 531385/526 (72%) musculus(Mouse), 531 aa.


[0474] PFam analysis predicts that the NOV28a protein contains the domains shown in the Table 28E.
151TABLE 28EDomain Analysis of NOV28aIdentities/NOV28aSimilarities forMatchthe MatchedExpectPfam DomainRegionRegionValuecyclin: domain 1 of 1 46 . . . 19028/163(17%)0.002286/163(53%)Srg: domain 1 of 1221 . . . 2304/10(40%)6.710/10(100%)transcript_fac2: domain 1235 . . . 25312/19(63%)0.86of 115/19(79%)cyclin_C: domain 1 of 1196 . . . 31122/139(16%)2.665/139(47%)



Example 29

[0475] The NOV29 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 29A.
152TABLE 29ANOV29 Sequence AnalysisSEQ ID NO:991069 bpNOV29a,CGGGGCCTGGTCGGCAGCTGGGCCGCCATGGAGTCCACGCTGGGCGCGGGCATCGTGACG59245-01 DNA SequenceTAGCCGAGGCGCTACAGAACCAGCTAGCCTGGCTGGAGAACGTGTGGCTCTGGATCACCTTTCTGGGCGATCCCAAGATCCTCTTTCTGTTCTACTTCCCCGCGGCCTACTACGCCTCCCGCCGTGTGGGCATCGCGGTGCTCTGGATCAGCCTCATCACCGAGTGGCTCAACCTCATCTTCAAGTGGTTTCTTTTTGGAGACAGGCCCTTTTGGTGGGTCCATGAGTCTGGTTACTACAGCCAGGCTCCAGCCCAGGTTCACCAGTTCCCCTCTTCTTGTGAGACTGGTCCAGGTGGCAGCCCTTCTGGACACTGCATGATCACAGGAGCAGCCCTCTGGCCCATAATGACGGCCCTGTCTTCGCAGGTGCGCTGGGTAAGGGTGATGCCTAGCCTGGCTTATTGCACCTTCCTTTTGGCGGTTGGCTTGTCGCGAATCTTCATCTTAGCACATTTCCCTCACCAGGTGCTGGCTGGCCTAATAACTGGTTGGCTGATGACTCCCCGAGTGCCTATGGAGCGGGAGCTAAGCTTCTATGGGTTGACTGCACTGGCCCTCATGCTAGGCACCAGCCTCATCTATTGGACCCTCTTTACACTGGGCCTGGATCTTTCTTGGTCCATCAGCCTAGCCTTCAAGTGGTGTGAGCGGCCTGAGTGGATACACGTGGATAGCCGGCCCTTTGCCTCCCTGAGCCGTGACTCAGGGGCTGCCCTGGGCCTGGGCATTGCCTTGCACTCTCCCTGCTATGCCCAGGTGCGTCGGGCACAGCTGGGAAATGGCCAGAAGATAGCCTGCCTTGTGCTGGCCATGGGGCTGCTGGGCCCCCTGGACTGGCTGGGCCACCCCCCTCAGATCAGCCTCTTCTACATTTTCAATTTCCTCAAGTACACCCTCTGGCCATGCCTAGTCCTGGCCCTCGTGCCCTGGGCAGTGCACATGTTCAGTGCCCAGGAAGCACCGCCCATCCACTCTTCCTGACTTCTTGTGTGCCTCCCTTTCCTTTCCCORF Start: ATG at 28ORF Stop: TGA at 1039SEQ ID NO:100337 aaMW at 37808.0 kDNOV29a,MESTLGAGIVIAEALQNQLAWLENVWLWITFLGDPKILFLFYFPAAYYASRRVGIAVLCG59245-01 Protein SequenceWISLITEWLNLIFKWFLFGDRPFWWVHESGYYSQAPAQVHQFPSSCETGPGGSPSGHCMITGAALWPIMTALSSQVRWVRVMPSLAYCTFLLAVGLSRIFILAHFPHQVLAGLITGWLMTPRVPMERELSFYGLTALALMLGTSLIYWTLFTLGLDLSWSISLAFKWCERPEWIHVDSRPFASLSRDSGAALGLGIALHSPCYAQVRRAQLGNGQKIACLVLAMGLLGPLDWLGHPPQISLFYIFNFLKYTLWPCLVLALVPWAVEMFSAQEAPPIHSSSEQ ID NO:1011386 bpNOV29b,TGAGTCTGTACTTTCCGCCCTGGAGCAAGCCGGGGCCTGGTCGGCAGCTGGGCCGCCACG59245-01 DNA SequenceTGGAGTCCACGCTGGGCGCGGGCATCGTGATAGCCGAGGCGCTACAGAACCAGCTAGCCTGGCTGGAGAACGTGTGGCTCTGGATCACCTTTCTGGGCGATCCCAAGATCCTCTTTCTGTTCTACTTCCCCGCGGCCTACTACGCCTCCCGCCGTGTGGGCATCGCGGTGCTCTGGATCAGCCTCATCACCGAGTGGCTCAACCTCATCTTCAAGTGGTTTCTTTTTGGAGACAGGCCCTTTTGGTGGGTCCATGAGTCTGGTTACTACAGCCAGGCTCCAGCCCAGGTTCACCAGTTCCCCTCTTCTTGTGAGACTGGTCCAGGCAGCCCTTCTGGACACTGCATGATCACAGGAGCAGCCCTCTGGCCCATAATGACGGCCCTGTCTTCGCAGGTGGCCACTCGGGCCCGCAGCCGCTGGGTAAGGGTGATGCCTAGCCTGGCTTATTGCACCTTCCTTTTGGCGGTTGGCTTGTCGCGAATCTTCATCTTAGCACATTTCCCTCACCAGGTGCTGGCTGGCCTAATAACTGGCGCTGTCCTGGGCTGGCTGATGACTCCCCGAGTGCCTATGGAGCGGGAGCTAAGCTTCTATGGGTTGACTGCACTGGCCCTCATGCTAGGCACCAGCCTCATCTATTGGACCCTCTTTACACTGGGCCTGGATCTTTCTTGGTCCATCAGCCTAGCCTTCAAGTGGTGTGAGCGGCCTGAGTGGATACACGTGGATAGCCGGCCCTTTGCCTCCCTGAGCCGTGACTCAGGGGCTGCCCTGGGCCTGGGCATTGCCTTGCACTCTCCCTGCTATGCCCAGGTGCGTCGGGCACAGCTGGGAAATGGCCAGAAGATAGCCTGCCTTGTGCTGGCCATGGGGCTGCTGGGCCCCCTGGACTGGCTGGGCCACCCCCCTCAGATCAGCCTCTTCTACATTTTCAATTTCCTCAAGTACACCCTCTGGCCATGCCCAGTCCTGGCCCTCGTGCCCTGGGCAGTGCACATGTTCAGTGCCCAGGAAGCACCGCCCATCCACTCTTCCTGACTTCTTGTGTGCCTCCCTTTCCTTTCCCTCCCACAAAGCCAACACTCTGTGACCACCACACTCCAGGAGGCAGCCCCATCCCCTTCCAGCCCCTAAGTAGGCCCTCCCCTCCCTAAATCTGCTTCCGCACCACCTGGTCTTAGCCCCAAAGATGGGCCTTCTCTCTCCCAGATAAGTTGGTCCTCCCTCTGCCTTTCCTCTCAAGCCCCCAAAGAGCAAAGGCAACAGCAAGACCAGCGGGTTCTTGCAACACTGTGAGGGGCAGCCAGGGCGGAAAGTACAGACTCAORF Start: ATG at 58ORF Stop: TGA at 1096SEQ ID NO:102346 aaMW at 38718.0 kDNOV29b,MESTLGAGIVIAEALQNQLAWLENVWLWITFLGDPKILFLFYFPAAYYASRRVGIAVLCG59245-01 Protein SequenceWISLITEWLNLIFKWFLFGDRPFWWVHESGYYSQAPAQVHQFPSSCETGPGSPSGHCMITGAALWPIMTALSSQVATRARSRWVRVMPSLAYCTFLLAVGLSRIFILAHFPHQVLAGLITGAVLGWLMTPRVPMERELSFYGLTALALMLGTSLIYWTLFTLGLDLSWSISLAFKWCERPEWIHVDSRPFASLSRDSGAALGLGIALHSPCYAQVRRAQLGNGQKIACLVLAMGLLGPLDWLGHPPQISLFYIFNFLKYTLWPCPVLALVPWAVHMFSAQEAPPIHSS


[0476] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 29B.
153TABLE 29BComparison of NOV29a against NOV29b.NOV29aIdentities/Residues/Similarities forProteinMatchthe MatchedSequenceResiduesRegionNOV29b1 . . . 337335/347 (96%)1 . . . 346335/347 (96%)


[0477] Further analysis of the NOV29a protein yielded the following properties shown in Table 29C.
154TABLE 29CProtein Sequence Properties NOV29aPSort0.6850 probability located in endoplasmic reticulumanalysis:(membrane); 0.6400 probability located in plasmamembrane; 0.4600 probability located in Golgi body;0.1000 probability located in endoplasmic reticulum (lumen)SignalPLikely cleavage site between residues 41 and 42analysis:


[0478] A search of the NOV29a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 29D.
155TABLE 29DGeneseq Results for NOV29aNOV29aIdentities/Residues/Similarities forGeneseqProtein/Organism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAM79500Human protein SEQ ID NO 3146 -1 . . . 337336/347 (96%)0.0Homo sapiens, 382 aa.37 . . . 382 336/347 (96%)[WO200157190-A2, 9 AUG2001]AAB42637Human ORFX ORF24011 . . . 337328/348 (94%)0.0polypeptide sequence SEQ ID31 . . . 377 328/348 (94%)NO:4802 - Homo sapiens, 377 aa.[WO200058473-A2, 5 OCT2000]AAB85355Human phosphatase (PP) (clone ID1 . . . 305297/315 (94%) e−1741269556CD1) - Homo sapiens, 3851 . . . 314298/315 (94%)aa. [WO200153469-A2, 26 JUL2001]AAM78516Human protein SEQ ID NO 1178 -1 . . . 337266/341 (78%) e−146Homo sapiens, 404 aa.125 . . . 404 272/341 (79%)[WO200157190-A2, 9 AUG2001]AAB25679Human secreted protein sequence198 . . . 337 140/140 (100%)6e−81encoded by gene 15 SEQ ID1 . . . 140140/140 (100%)NO:68 - Homo sapiens, 141 aa.[WO200043495-A2, 27 JUL 2000]


[0479] In a BLAST search of public sequence databases, the NOV29a protein was found to have homology to the proteins shown in the BLASTP data in Table 29E.
156TABLE 29EPublic BLASTP Results for NOV29aIdentities/NOV29aSimilaritiesProteinResidues/for theAccessionMatchMatchedExpectNumberProtein/Organism/LengthResiduesPortionValueAAH21574HYPOTHETICAL 38.7 KDA1 . . . 337336/347 (96%)0.0PROTEIN - Homo sapiens1 . . . 346336/347 (96%)(Human), 346 aa.Q9BUM1HYPOTHETICAL 40.1 KDA1 . . . 337336/347 (96%)0.0PROTEIN - Homo sapiens15 . . . 360 336/347 (96%)(Human), 360 aa (fragment).O42153Glucose-6-phosphatase (EC8 . . . 323127/333 (38%)1e−593.1.3.9) (G6Pase) (G-6-Pase) -8 . . . 339184/333 (55%)Haplochromis nubilus, 352 aa.Q98UF8GLUCOSE-6-PHOSPHATASE -8 . . . 323123/333 (36%)2e−57Sparus aurata (Gilthead sea8 . . . 337185/333 (54%)bream), 350 aa.Q9Z186GLUCOSE-6-PHOSPHATASE -7 . . . 325128/343 (37%)5e−56Mus musculus (Mouse), 355 aa.7 . . . 345188/343 (54%)


[0480] PFam analysis predicts that the NOV29a protein contains the domains shown in the Table 29F.
157TABLE 29FDomain Analysis of NOV29aIdentities/SimilaritiesPfamNOV29afor theExpectDomainMatch RegionMatched RegionValuePAP2: domain 1 of 151 . . . 19038/175 (22%)0.0003795/175 (54%)



Example 30

[0481] The NOV30 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 30A.
158TABLE 30ANOV39 Sequence AnalysisSEQ ID NO:1031624 bpNOV30a,ATGGAACTGAAGGCCGAGGAGGAGGAGGTGGGTGGCGTCCAGCCGGTGGACTTGGTGGCG59241-01 DNA SequenceCCTTTGCCAACAGCTGCACCCTCCATGGCACCAACCACATTTTTGTGGAGGGGGGTCCAGGGCCAAGGCAGGTGCTGTGGGCGGTGGCCTTTGTCCTGGCACTGGGTGCCTTCCTGTGCCAGGTAGGGGACCGCGTTGCTTATTACCTCAGCTACCCACACGTGACCCTTCTAAACGAAGTGGCCACCACGGAGCTGGCCTTCCCGGCAGTCACCCTCTGCAACACTAATGCTGTGCGGCTGTCCCAGCTCAGCTACCCTGACTTGCTTTATTTGGCCCCCATGCTGGGACTGGATGAAAGTGATGACCCCGGGGTGCCCCTCGCTCCACCGGGCCCTGAGGCCTTCTCTGGGGAGCCCTTTAACCTGCACCGCTTCTACAATCGCTCCTGCCACCGGCTGGAGGACATGCTGCTCTATTGCTCCTACCAAGGGGGACCCTGCGGCCCTCACAACTTCTCAGTGGTGTTCACACGCTATGGAAAGTGCTACACGTTCAACTCGGGCCGAGATGGGCGGCCGCGGCTGAAGACCATGAAGGGTGGGACGGGCAATGGGCTGGAAATCATGCTGGACATCCAGCAGGACGAGTACCTGCCTGTGTGGGGGGAGACTGACGAGACGTCCTTCGAAGCAGGCATCAAAGTGCAGATCCATAGTCAGGATGAACCTCCTTTCATCGACCAGCTGGGCTTTGGCGTGGCCCCAGGCTTCCAGACCTTTGTGGCCTGCCAGGAGCAGCGGATCTACCTGCCCCCACCCTGGGGCACCTGCAAAGCTGTTACCATGGACTCGGATTTCTTCGACTCCTACAGCATCACTGCCTGCCGCATCGACTGTGAGACGCGCTACCTGGTGGAGAACTGCAACTGCCGCATGGTGCACATGCCAGGTGATGCCCCATACTGTACTCCAGAGCAGTACAAGGAGTGTGCAGATCCTGCTCTGGACTTCCTGGTGGAGAAGGACCAGGAGTACTGCGTGTGTGAAATGCCTTGCAACCTGACCCGCTATGGCAAAGAGCTGTCCATGGTCAAGATCCCCAGCAAAGCCTCAGCCAAGTACCTGGCCAAGAAGTTCAACAAATCTGAGCAATACATAGGGGAGAACATCCTGGTGCTGGACATTTTCTTTGAAGTCCTCAACTATGAGACCATTGAACAGAAGAAGGCCTATGAGATTGCAGGGCTCCTGGGTGACATCGGGGGCCAGATGGGGCTGTTCATCGGGGCCAGCATCCTCACGGTGCTGGAGCTCTTTGACTACGCCTACGAGGTAGTCATTAAGCACAAGCTGTGCCGACGAGGAAAATGCCAGAAGGAGGCCAAAAGGAGCAGTGCGGACAAGGGCGTGGCCCTCAGCCTGGACGACGTCAAAAGACACAACCCGTGCGAGAGCCTTCGGGGCCACCCTGCCGGGATGACATACGCTGCCAACATCCTACCTCACCATCCGGCCCGAGGCACGTTCGAGGACTTTACCTGCTGAGCCCCGCAGGCCGCTGAACCAAAGGCCTAGATGGGGAGGACTAGGAGAGCGAGGGGGCCCCCAGCTGCCTCCTCACATCORF Start: ATG at 1ORF Stop: TGA at 1543SEQ ID NO:104514 aaMW at 57221.7 kDNOV3a,MELKAEEEEVGGVQPVDLVAFANSCTLHGTNHIFVEGGPGPRQVLWAVAFVLALGAFLCG59241-01 Protein SequenceCQVGDRVAYYLSYPHVTLLNEVATTELAFPAVTLCNTNAVRLSQLSYPDLLYLAPMLGLDESDDPGVPLAPPGPEAFSGEPFNLHRFYNRSCHRLEDMLLYCSYQGGPCGPHNFSVVFTRYGKCYTFNSGRDGRPRLKTMKGGTGNGLEIMLDIQQDEYLPVWGETDETSFEAGIKVQIHSQDEPPFIDQLGFGVAPGFQTFVACQEQRIYLPPPWGTCKAVTMDSDFFDSYSITACRIDCETRYLVENCNCRMVHMPGDAPTCTPEQYKECADPALDFLVEKDQEYCVCEMPCNLTRYGKELSMVKIPSKASAKYLAKKFNKSEQYIGENILVLDIFFEVLNYETIEQKKAYEIAGLLGDIGGQMGLFIGASILTVLELFDYAYEVVIKHKLCRRGKCQKEAKRSSADKGVALSLDDVKRHNPCESLRGHPAGMTYAANILPHHPARGTFEDFTC


[0482] Further analysis of the NOV30a protein yielded the following properties shown in Table 30B.
159TABLE 30BProtein Sequence Properties NOV30aPSort0.7900 probability located in plasma membrane; 0.3000analysis:probability located in Golgi body; 0.2000 probabilitylocated in endoplasmic reticulum (membrane);0.1000 probability located in mitochondrial inner membraneSignalPLikely cleavage site between residues 60 and 61analysis:


[0483] A search of the NOV30a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 30C.
160TABLE 30CGeneseq Results for NOV30aNOV30aIdentities/Residues/Similarities forGeneseqProtein/Organism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAY69178A rat acid-sensitive cationic 1 . . . 514488/515 (94%)0.0channel 1B (rASIC1B) - Rattus sp,47 . . . 559497/515 (95%)559 aa. [WO200008149-A2, 17FEB 2000]AAY03186Rat Acid sensitive ion channel 1 . . . 514488/515 (94%)0.0protein sequence - Rattus sp, 513 1 . . . 513498/515 (95%)aa. [WO9911784-A1, 11 MAR1999]AAW68507Rat acid sensing ionic channel 1B - 1 . . . 514488/515 (94%)0.0Rattus sp, 559 aa. [WO9835034-47 . . . 559497/515 (95%)A1, 13 AUG 1998]AAY69175A rat acid-sensitive cationic 1 . . . 514416/527 (78%)0.0526 aa. [WO200008149-A2, 17 1 . . . 526445/527 (83%)FEB 2000]AAY03188Rat Acid sensitive ion channel 1 . . . 514416/527 (78%)0.0alpha protein sequence - Rattus sp, 1 . . . 526445/527 (83%)526 aa. [WO9911784-A1, 11MAR 1999]


[0484] In a BLAST search of public sequence databases, the NOV30a protein was found to have homology to the proteins shown in the BLASTP data in Table 30D.
161TABLE 30DPublic BLASTP Results for NOV30aIdentities/NOV30aSimilaritiesProteinResidues/for theAccessionMatchMatchedExpectNumberProtein/Organism/LengthResiduesPortionValueQ91YB8ION CHANNEL - Rattus norvegicus1 . . . 514489/515 (94%)0.0(Rat), 559 aa.47 . . . 559 498/515 (95%)O88762ASIC-BETA - Rattus norvegicus1 . . . 514488/515 (94%)0.0(Rat), 513 aa.1 . . . 513498/515 (95%)P55926Amiloride-sensitive brain sodium1 . . . 514416/527 (78%)0.0channel BNaC2 (Amiloride-sensitive1 . . . 526445/527 (83%)cation channel neuronal 2) (Protongated cation channel ASIC1) - Rattusnorvegicus (Rat), 526 aa.P78348Amiloride-sensitive brain sodium1 . . . 514421/575 (73%)0.0channel BNaC2 (Amiloride-sensitive1 . . . 574447/575 (77%)cation channel neuronal 2) - Homosapiens (Human), 574 aa.Q99NA1PROTON-GATED CATION175 . . . 514 334/341 (97%)0.0CHANNEL SUBUNIT ASIC-86 . . . 425 337/341 (97%)BETA2 - Rattus norvegicus (Rat),425 aa.


[0485] PFam analysis predicts that the NOV30a protein contains the domains shown in the Table 30E.
162TABLE 30EDomain Analysis of NOV30aIdentities/SimilaritiesPfamNOV30afor theExpectDomainMatch RegionMatched RegionValueASC: domain 1 of 2 21 . . . 11834/106(32%)1.6e−29 79/106(75%)ASC: domain 2 of 2145 . . . 442133/351(38%)2.1e−139281/351(80%)



Example 31

[0486] The NOV31 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 31A.
163TABLE 31ANOV31 Sequence AnalysisSEQ ID NO:1051949 bpNOV31a,TGCCTGGCTATGGCCCGACTGCTCAGGTCTGCAACCTGGGAGCTGTTCCCCTGGAGGGCG58602-01 DNA SequenceGCTACTGCTCCCAGTCCCTGCAGGGAGAGCTCTGCAGGGACTTCGTAGAGGCTCTGAAGGCCGTGGTGGGCGGCTCCCACGTGTCCACTGCCGCGGTGGTCCGAGAGCAGCACGGGCGCGATGAGTCGGTGCACAGGTGCGAACCTCCTGATGCTGTGGTGTGGCCCCAGAACGTGGAGCAGGTCAGCCGGCTGGCAGCCCTGTGCTATCGCCAAGGTGTGCCCATCATCCCATTCGGCACCGGCACCGGGCTTGAGGGTGGCGTCTGTGCTGTGCAGGGCGGCGTCTGCGTTAACCTGACGCATATGGACCGAATCCTGGAGCTGAACCAGGAGGACTTCTCTGTGGTGGTGGAGCCAGGTGTCACCCGCAAAGCCCTCAACGCCAACCTGCGGGACAGCGGCCTCTGGTTTCCTCCAGACCCAGGCGCGGACGCCTCTCTCTGTGGCATGGCGGCCACCGGGGCGTCGGGGACCAACGCGGTCCGCTACGGCACCATGCGGGACAACGTGCTCAACCTGGAGGTGGTGCTGCCCGACGGGCGGCTGCTGCACACGGCGGGCCGAGGCCTCATCACAGATTCCACTGCTGCATTCCCCCACATCAGCCCCACTGAGTGCTTTTCCCAGGGGCCAGGGCCTCATGTCAATTCTCCTCACCCTGCCCCTGAGGCCACAGTGGCCGCCACGTGTGCGTTCCCCAGTGTCCAGGCTGCTGTGGACAGCACTGTACACATCCTCCAGGCTGCAGTGCCCGTAGCCCGCATTGAGTTCCTGGATGAAGTCATGATGGATGCCTGCAACAGGTACAGCAAGCTGAATTGCTTAGTGGCGCCCACACTCTTCCTGGAGTTCCATGGCTCCCAGCAGGCACTGGAGGAGCAGCTGCAGCGCACAGAGGAGATAGTCCAGCAGAACGGAGCCTCTGACTTCTCCTGGGCCAAGGAGGCCGAGGAGCGCAGCCGGCTTTGGACAGCACGGCACAATGCCTGGTACGCAGCCCTGGCCACGCGGCCAGGCTGCAAGGGCTACTCCACGGATGTGTGTGTGCCCATCTCCCGGCTGCCGGAGATCGTGGTGCAGACCAAGGAGGATCTGAATGCCTCAGGACTCACAGGAAGCATTGTCGGGCATGTGGGTGACGGCAACTTCCACTGCATCCTGCTGGTCAACCCTGATGACGCCGAGGAACTGGGCAGGGTCAAGGCTTTTGCAGAACAGCTGGGCAGGCGGGCACTGGCTCTCCACGGAACGTGCACCGGGGGAGCATGGCATGGAATGGGCAAGCGGCAGCTGCTGCAGGAGGAGGTGGGCGCCGTGGGCGTGGAGACCATGCGGCAGCTCAAGGCCGTGCTAGACCCCCAAGGCCTCATGAATCCAGGCAAAGTGCTGTGAAGGGGGTCTGAGCACTTAGCCCACAAGTTCCCTGACTACGGAGCCGGTTCTGGAACTTTTCTTCATGCCACGGCCCCTGCAAGGAAATAGATGCTGAGGCAGTCTTCCTGCCAGCGAGCCCACTGTATCTGGGCCCAAGGCCAGAGGGCCCAGAGAGAAGCCTGAGCACCGTGTTACCTCCCTGGCCCTCTGGCTGGCCCCAGGAGCCTTTGGTTCAGTAAACGACCCAGGGTGGTTCCCAGCAAAGCTGCTTCCTCTCTGCTCCTACGCATCCTGTCCTGGCGGGAAGAGAGCGTCTGGGTCCATTCAAGACTCTGATGACACCCCTCCCCGAGGCCTCCCACTGCCGGGGTCCCAGGACCCTTCCCCCTTCACCTGGTGACAGGAACACTCCTTTCCTGGTATGGAACGTGAGCTCCCGTGACATGATGATAGGTCTTCTCCTTGGGGCCTCCCCCAATAAATCTGTAATAAACCTGAAACCCACCTACAGCTAAORF Start: ATG at 10ORF Stop: TGA at 1450SEQ ID NO:106480 aaMW at 51629.1 kDNOV31a,MARLLRSATWELFPWRGYCSQSLQGELCRDFVEALKAVVGGSHVSTAAVVREQHGRDECG58602-01 Protein SequenceSVHRCEPPDAVVWPQNVEQVSRLAALCYRQGVPIIPFGTGTGLEGGVCAVQGGVCVNLTHMDRILELNQEDFSVVVEPGVTRKALNAHLRDSGLWFPPDPGADASLCGMAATGASGTNAVRYGTMRDNVLNLEVVLPDGRLLHTAGRGLITDSTAAFPHISPTECFSQGPGPHVNSPHPAPEATVAATCAFPSVQAAVDSTVHILQAAVPVARIEFLDEVMMDACNRYSKLNCLVAPTLFLEFHGSQQALEEQLQRTEEIVQQNGASDFSWAKEAEERSRLWTARHNAWYAALATRPGCKGYSTDVCVPISRLPEIVVQTKEDLNASGLTGSIVGHVGDGNFHCILLVNPDDAEELGRVKAFAEQLGRRALALHGTCTGEHGIGMGKRQLLQEEVGAVGVETMRQLKAVLDPQGLMNPGKVL


[0487] Further analysis of the NOV31a protein yielded the following properties shown in Table 31B.
164TABLE 31BProtein Sequence Properties NOV31aPSort0.6574 probability located in mitochondrial matrix space;analysis:0.3502 probability located in mitochondrial inner membrane;0.3502 probability located in mitochondrial intermembranespace; 0.3502 probability located in mitochondrial outermembraneSignalPLikely cleavage site between residues 20 and 21analysis:


[0488] A search of the NOV31a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 31C.
165TABLE 31CGeneseq Results for NOV31aNOV31aIdentities/Residues/Similarities forGeneseqProtein/Organism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueABB10446Human cDNA SEQ ID NO: 754 -1 . . . 9691/96(94%)8e−49Homo sapiens, 115 aa.15 . . . 11092/96(95%)[WO200154474-A2, 2 AUG 2001]AAE09597Human gene 5 encoded novel1 . . . 9691/96(94%)8e−49protein HDPMT22, SEQ ID NO:33 -15 . . . 11092/96(95%)Homo sapiens, 115 aa.[WO200155311-A2, 2 AUG 2001]AAM52368GIP12-C4 protein - Arabidopsis66 . . . 20369/138(50%)9e−34thaliana, 159 aa. [FR2806095-A1, 3 . . . 14098/138(71%)14 SEP 2001]AAG92286C glutamicum protein fragment SEQ46 . . . 477108/486(22%)2e−22ID NO: 6040 - Corynebacterium25 . . . 502186/486(38%)glutamicum, 948 aa. [EP1108790-A2, 20 JUN 2001]AAB79309Corynebacterium glutamicum SMP46 . . . 477108/486(22%)2e−22protein sequence SEQ ID NO:134 -22 . . . 499186/486(38%)Corynebacterium glutamicum, 945aa. [WO200100844-A2, 4 JAN2001]


[0489] In a BLAST search of public sequence databases, the NOV31a protein was found to have homology to the proteins shown in the BLASTP data in Table 31D.
166TABLE 31DPublic BLASTP Results for NOV31aIdentities/NOV31aSimilaritiesProteinResidues/for theAccessionMatchMatchedExpectNumberProtein/Organism/LengthResiduesPortionValueQ9D6354733401P21RIK PROTEIN - Mus 1 . . . 480394/483 (81%)0.0musculus (Mouse), 481 aa. 1 . . . 481423/483 (87%)Q19965F32D8.4 PROTEIN - Caenorhabditis20 . . . 480221/466 (47%)e−121elegans, 912 aa.445 . . . 909 307/466 (65%)CAD16371PUTATIVE D-LACTATE32 . . . 479226/454 (49%)e−119DEHYDROGENASE20 . . . 469300/454 (65%)(CYTOCHROME)OXIDOREDUCTASE PROTEIN(EC 1.1.2.4) - Ralstoniasolanacearum (Pseudomonassolanacearum), 472 aa.A89201protein F32D8.4 [imported] -30 . . . 480214/469 (45%)e−115Caenorhabditis elegans, 870 aa.399 . . . 867 296/469 (62%)AAL51780D-LACTATE DEHYDROGENASE41 . . . 480209/444 (47%)e−114(CYTOCHROME) (EC 1.1.2.4) -28 . . . 467286/444 (64%)Brucella melitensis, 468 aa.


[0490] PFam analysis predicts that the NOV31a protein contains the domains shown in the Table 31E.
167TABLE 31EDomain Analysis of NOV31aIdentities/SimilaritiesPfamNOV31afor theExpectDomainMatch RegionMatched RegionValueFAD_binding_4: 33 . . . 21470/208(34%)3.7e−56domain 1 of 1154/208(74%)FAD-oxidase_C:206 . . . 47991/307(30%)1.3e−58domain 1 of 1210/307(68%)



Example 32

[0491] The NOV32 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 32A.
168TABLE 32ANOV32 Sequence AnalysisSEQ ID NO:107698 bpNOV32a,CTCCTTCCTGTGCTCTTTATATGGACCAACAACTTCTCGTCCTTGGGGTCTCTGTGCACG58468-01 DNA SequenceAATATCAATTTTTTCACATTATCTTTTCTCCACAGACATGAGAGGGAAGGCATTTATTTTCCCTCAAGAATCAGCTACAGTCTATGTGTCCCTGATCCCCAAGGTGAAGAAGCCCCTGAAGAACTTCAAGCTTTGCCTGAAAACCTTCACAGACTTCACCTGCCCTTATAGCCTCTTCTACAGCACTCCGTCCCAGGACAATGAGCTGCTTCTCCTTGTCAACAAAATGGGAATGTATCTGCTGCACATTGGAAATGCTGCGGTCACTTTCAATGGCCCCACCCCCTGCCCTCGATCTCCTTATGCTTCGACCCATGTCAATGTGAGCTGGGAGTCTGCCTCTGGAATTGCTACACTCTGGGCAAATGGGAAGCTGGTGGGGAGGAAGGGTGTGTGGAAGGGGTACTCTGTGGGAGAAGAGGCTAAGATCATCCTGGGACAAGAGCAGGATTCCTTTGGGGGACATTTTGATGAAAATCAATCCTTTGTTGGGGTGATATGGGATGTGTTTTTGTGGGATCATGTGCTCCCTCCAAAGGAGATGTGTGACTCCTGTTACAGCGGCAGCCTCCTGAATCGGCATACCCTGACTTATGAAGATAATGGCTATGTGGTAACTAAGCCCAAGGTGTGGGCTTAAORF Start: ATG at 21ORF Stop: TAA at 696SEQ ID NO:108225 aaMW at 25265.8 kDNOV32a,MDQQLLVLGVSVQISIFSHYLFSTDMRGKAFIFPQESATVYVSLIPKVKKPLKNFKLCCG58468-01 Protein SequenceLKTFTDFTCPYSLFYSTRSQDNELLLLVNKMGMYLLHIGNAAVTFNGPTPCPRSPYASTHVNVSWESASGIATLWANGKLVGRKGVWKGYSVGEEAKIILGQEQDSFGGHFDENQSFVGVIWDVFLWDHVLPPKEMCDSCYSGSLLNRHTLTYEDNGYVVTKPKVWA


[0492] Further analysis of the NOV32a protein yielded the following properties shown in Table 32B.
169TABLE 32BProtein Sequence Properties NOV32aPSort0.5500 probability located in endoplasmic reticulumanalysis:(membrane); 0.3200 probability located in microbody(peroxisome); 0.2368 probability located in lysosome(lumen); 0.1000 probability located in endoplasmicreticulum (lumen)SignalPNo Known Signal Sequence Predictedanalysis:


[0493] A search of the NOV32a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 32C.
170TABLE 32CGeneseq Results for NOV32aNOV32aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAR74763Sermun amyloid P component,24 . . . 224 98/207 (47%)4e−48promoter sapm-Homo sapiens, 2 . . . 203136/207 (65%)204 aa. [WO9505394-A,23 Feb. 1995]AAR29923SAP-Homo sapiens, 223 aa. 7 . . . 224101/224 (45%)3e−47[WO9221364-A, 10 DEC. 1992] 5 . . . 222143/224 (63%)AAR29922CRP-Homo sapiens, 225 aa.14 . . . 224100/218 (45%)2e−43[WO9221364-A, 10 DEC. 1992]11 . . . 224132/218 (59%)AAR74769Female hamster protein, 1 fhp-24 . . . 222 95/206 (46%)6e−43Cricetus cricetus, 210 aa. 1 . . . 199132/206 (63%)[WO9505394-A, 23 FEB. 1995]AAY76844Human C reactive protein (CRP)24 . . . 224 98/208 (47%)1e−42sequence-Homo sapiens, 206 aa. 2 . . . 205128/208 (61%)[JP2000014388-A,18 JAN. 2000]


[0494] In a BLAST search of public sequence databases, the NOV32a protein was found to have homology to the proteins shown in the BLASTP data in Table 32D.
171TABLE 32DPublic BLASTP Results for NOV32aNOV32aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueQ9D8J81810030J14RIK PROTEIN-Mus 6 . . . 224130/220 (59%)5e−72musculus (Mouse), 219 aa. 4 . . . 218166/220 (75%)Q9D8V21810030J14RIK PROTEIN-Mus 6 . . . 190110/186 (59%)2e−58musculus (Mouse), 200 aa.20 . . . 200139/186 (74%)Q63913SERUM AMYLOID P-Cricetulus 1 . . . 224109/231 (47%)4e−51migratorius (Armenian hamster), 1 . . . 222152/231 (65%)223 aa.P23680Serum amyloid P-component 6 . . . 224105/224 (46%)7e−50precursor (SAP)-Rattus norvegicus 4 . . . 223145/224 (63%)(Rat), 228 aa.P15697Female protein precursor (FP) 1 . . . 222108/229 (47%)7e−50(Serum amyloid P-component)- 1 . . . 220151/229 (65%)Cricetulus migratorius (Armenianhamster), 231 aa.


[0495] PFam analysis predicts that the NOV32a protein contains the domains shown in the Table 32E.
172TABLE 32EDomain Analysis of NOV32aIdentities/PfamNOV32a MatchSimilarities forExpectDomainRegionthe Matched RegionValuepentaxin: domain 1 of29 . . . 221103/214 (48%)8e−761156/214 (73%)



Example 33

[0496] The NOV33 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 33A.
173TABLE 33ANOV33 Sequence AnalysisSEQ ID NO:1093350 bpNOV33a,TAATGAGGAGACTGAGTTTGTGGTGGCTGCTGAGCAGGGTCTGTCTGCTGTTGCCGCCCG58183-01 DNA SequenceGCCCTGCGCACTGGTGCTGGCCGGGGTGCCCAGCTCCTCCTCGCACCCGCAGCCCTGCCAGATCCTCAAGCGCATCGGGCACGCGGTGAGGGTGGGCGCGGTGCACTTGCAGCCCTGGACCACCGCCCCCCGCGCGGCCAGCCGCGCTCCGGACGACAGCCGAGCAGGAGCCCAGAGGGATGAGCCGGAGCCAGGGACTAGGCGGTCCCCGGCGCCCTCGCCGGGCGCACGCTGGTTGGGGAGCACCCTGCATGGCCGGGGGCCGCCGGGCTCCCGTAAGCCCGGGGAGGGCGCCAGGGCGGAGGCCCTGTGGCCACGGGACGCCCTCCTATTTGCCGTGGACAACCTGAACCGCGTGGAAGGGCTGCTACCCTACAACCTGTCTTTGGAAGTAGTGATGGCCATCGAGGCAGGCCTGGGCGATCTGCCACTTTTGCCCTTCTCCTCCCCTAGTTCGCCATGGAGCAGTGACCCTTTCTCCTTCCTGCAAAGTGTGTGCCATACCGTGGTGGTGCAAGGGGTGTCGGCGCTGCTCGCCTTCCCCCAGAGCCAGGGCGAAATGATGGAGCTCGACTTGGTCAGCTTAGTCCTGCACATTCCAGTGATCAGCATCGTGCGCCACGAGTTTCCACGGGAGAGTCAGAATCCCCTTCACCTACAACTGAGTTTAGAAAATTCATTAAGTTCTGATGCTGATGTCACTGTCTCAATCCTGACCATGAACAACTGGTACAATTTTAGCTTGTTGCTGTGCCAGGAAGACTGGAACATCACCGACTTCCTCCTCCTTACCCAGAATAATTCCAAGTTCCACCTTGGTTCTATCATCAACATCACCGCTAACCTCCCCTCCACCCAGGACCTCTTGAGCTTCCTACAGATCCAGCTTGAGAGTATTAAGAACAGCACACCCACAGTGGTGATGTTTGGCTGCGACATGGAAAGTATCCGGCGGATTTTCGAAATTACAACCCAGTTTGGGGTCATGCCCCCTGAACTTCGTTGGGTGCTGGGAGATTCCCAGAATGTGGAGGAACTGAGGACAGAGGGTCTGCCCTTAGGGCTCATTGCTCATGGAAAAACAACACAGTCTGTCTTTGAGCACTACGTACAAGATGCTATGGAGCTGGTCGCAAGAGCTGTAGCCACAGCCACCATGATCCAACCAGAACTTGCTCTCATTCCCAGCACGATGAACTGCATGGAGGTGGAAACTACAAATCTCACTTCAGGACAATATTTATCAAGGTTTCTAGCCAATACCACTTTCAGAGGCCTCAGTGGTTCCATCAGAGTAAAAGGTTCCACCATCGTCAGCTCAGAAAACAACTTTTTCATCTGGAATCTTCAACATCACCCCATGGGAAAGCCAATGTGGACCCGCTTGGGCAGCTGGCAGGGGGGAAAGATTGTCATGGACTATGGAATATGGCCAGAGCAGGCCCAGAGACACAAAACCCACTTCCAACATCCAAGTAAGCTACACTTGAGAGTGGTTACCCTGATTGAGCATCCTTTTGTCTTCACAAGGGAGGTAGATGATGAAGGCTTGTGCCCTGCTGGCCAACTCTGTCTAGACCCCATGACTAATGACTCTTCCACATTGGACAGCCTTTTTAGCAGCCTCCATAGCAGTAATGATACAGTGCCCATTAAATTCAAGAAGTGCTGCTATGGATATTGCATTGATCTGCTGGAAAAGATAGCAGAAGACATGAACTTTGACTTCGACCTCTATATTGTAGGGGATGGAAAGTATGGAGCATGGAAAAATGGGCACTGGACTGGGCTAGTGGGTGATCTCCTGAGAGGGACTGCCCACATGGCAGTCACTTCCTTTAGCATCAATACTGCACGGAGCCAGGTGATAGATTTCACCAGCCCTTTCTTCTCCACCAGCTTGGGCATCTTAGTGAGGACCCGAGATACAGCAGCTCCCATTGGAGCCTTCATGTGGCCACTCCACTGGACAATGTGGCTGGGGATTTTTGTGGCTCTGCACATCACTGCCGTCTTCCTCACTCTGTATGAATGGAAGAGTCCATTTGGTTTGACTTCCAAGGCGCGAAATAGAAGTAAAGTCTTCTCCTTTTCTTCAGCCTTGAACATCTGTTATGCCCTCTTGTTTGGCAGAACAGTGGCCATCAAACCTCCAAAATGTTGGACTGGAAGGTTTCTAATGAACCTTTGGGCCATTTTCTGTATGTTTTGCCTTTCCACATACACGGCAAACTTGCCTGCTGTCATGGTAGGTGAGAAGATCTATGAAGAGCTTTCTGGAATACATGACCCCAAGTTACATCATCCTTCCCAAGGATTCCGCTTTGGAACTGTCCGAGAAAGCAGTGCTGAAGATTATGTGAGACAAAGTTTCCCAGAGATGCATGAATATATGAGAAGGTACAATGTTCCAGCCACCCCTGATGGAGTGGAGTATCTGAAGAATGATCCAGAGAAACTAGACGCCTTCATCATGGACAAAGCCCTTCTGGATTATGAAGTGTCAATAGATGCTGACTGCAAACTTCTCACTGTGGGGAAGCCATTTGCCATAGAAGGTTACGGCATTGGCCTCCCACCCAACTCTCCATTGACCGCCAACATATCCGAGCTAATCAGTCAATACAAGTCACATGGGTTTATGGATATGCTCCATGACAAGTGGTACAGGGTGGTTCCCTGTGGCAAGAGAAGTTTTGCTGTCACGGAGACTTTGCAAATGGGCATCAAACACTTCTCTGGGCTCTTTGTGCTGCTGTGCATTGGATTTGGTCTGTCCATTTTGACCACCATTGGTGAGCACATAGTATACAGGCTGCTGCTACCACGAATCAAAAACAAATCCAAGCTGCAATACTGGCTCCACACCAGCCAGAGATTACACAGAGCAATAAATACATCATTTATAGAGGAAAAGCAGCAGCATTTCAAGACCAAACGTGTGGAAAAGAGATCTAATGTGGGACCCCGTCAGCTTACCGTATGGAATACTTCCAATCTGAGTCATGACAACCGACGGAAATACATCTTTAGTGATGAGGAAGGACAAAACCAGCTGGGCATCCGGATCCACCAGGACATCCCCCTCCCTCCAAGGAGAAGAGAGCTCCCTGCCTTGCGGACCACCAATGGGAAAGCAGACTCCCTAAATGTATCTCGGAACTCAGTGATGCAGGAACTCTCAGAGCTCGAGAAGCAGATTCAGGTGATCCGTCAGGAGCTGCAGCTGGCTGTGAGCAGGAAAACGGAGCTGGAGGAGTATCAAAGGACAAGTCGGACTTGTGAGTCCTAGORF Start: ATG at 3ORF Stop: TAG at 3348SEQ ID NO:1101115 aaMW at 125453.7 kDNOV33a,MRRLSLWWLLSRVCLLLPPPCALVLAGVPSSSSHPQPCQILKRIGHAVRVGAVHLQPWCG58183-01 Protein SequenceTTAPRAASRAPDDSRAGAQRDEPEPGTRRSTAPSPGARWLGSTLHGRGPPGSRKPGEGARAEALWPRDALLFAVDNLNRVEGLLPYNLSLEVVNAIEAGLGDLPLLPFSSPSSPWSSDPFSFLQSVCHTVVVQGVSALLAFPQSQGEMMELDLVSLVLHIPVISIVRHEFPRESQNPLHLQLSLENSLSSDADVTVSILTMNNWYNFSLLLCQEDWNITDFLLLTQNNSKFHLGSIINITANLPSTQDLLSFLQIQLESIKNSTPTVVMFGCDMESIRRIFEITTQFGVMPPELRWVLGDSQNVEELRTEGLPLGLIAHGKTTQSVFEHYVQDAMELVARAVATATMIQPELALIPSTMNCMEVETTNLTSGQYLSRFLANTTFRGLSGSIRVKGSTIVSSENNFFIWNLQHDPMGKPMWTRLGSWQGCKIVMDYGIWPEQAQRNKTHFQHPSKLHLRVVTLIEHPFVFTREVDDEGLCPAGQLCLDPMTNDSSTLDSLFSSLHSSNDTVPIKFKKCCYGYCIDLLEKIAEDMNFDFDLYIVGDGKYGAWKNGHWTGLVGDLLRGTAHMAVTSFSINTARSQVIDFTSPFFSTSLGILVRTRDTAAPIGAFMWPLHWTMWLGIFVALHITAVFLTLYEWKSPFGLTSKGRNRSKVFSFSSALNICYALLFGRTVAIKPPKCWTGRFLMNLWAIFCMFCLSTYTANLAAVMVGEKIYEELSGIHDPKLNHPSQGFRFGTVRESSAEDYVRQSFPEMHEYMRRYNVPATPDGVEYLKNDPEKLDAFIMDKALLDYEVSIDADCKLLTVGKPFAIEGYGIGLPPNSPLTANISELISQYKSHGFMDMLHDKWYRVVPCGKRSFAVTETLQNGIKHFSGLFVLLCIGFGLSILTTIGEHIVYRLLLPRIKNKSKLQYWLHTSQRLHRAINTSFIEEKQQHFKTKRVEKRSNVGPRQLTVWNTSNLSHDNRRKYIFSDEEGQNQLGIRIHQDIPLPPRRRELPALRTTNGKADSLNVSRNSVMQELSELEKQIQVIRQELQLAVSRKTELEEYQRTSRTCES


[0497] Further analysis of the NOV33a protein yielded the following properties shown in Table 33B.
174TABLE 33BProtein Sequence Properties NOV33aPSort0.6400 probability located in plasma membrane; 0.4600analysis:probability located in Golgi body; 0.3700 probabilitylocated in endoplasmic reticulum (membrane); 0.1000probability located in endoplasmicreticulum (lumen)SignalPLikely cleavage site between residues 34 and 35analysis:


[0498] A search of the NOV33a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 33C.
175TABLE 33CGeneseq Results for NOV33aNOV33aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAU02199Human glutamate receptor-like 95 . . . 1103508/1047 (48%)0.0protein, MEM4-Homo sapiens, 6 . . . 1007680/1047 (64%)1043 aa. [WO200144473-A2,21 JUN. 2001]AAB42494Human ORFX ORF2258 95 . . . 985484/912 (53%)0.0polypeptide sequence SEQ ID 6 . . . 885635/912 (69%)NO: 4516-Homo sapiens,901 aa. [WO200058473-A2,5 OCT. 2000]AAU02198Human glutamate receptor-like532 . . . 1103361/579 (62%)0.0protein, MEM3-Homo sapiens,362 . . . 935448/579 (77%)971 aa. [WO200144473-A2,21 JUN. 2001]AAU02197Human glutamate receptor-like532 . . . 1103352/579 (60%)0.0protein, MEM2-Homo sapiens,362 . . . 929437/579 (74%)965 aa. [WO200144473-A2,21 JUN. 2001]AAR44192Rat NMDA receptor subunit,175 . . . 1023245/873 (28%)2e−83NR2A-Rattus rattus, 1464 aa. 77 . . . 911425/873 (48%)[DE4216321-A, 18-NOV. 1993]


[0499] In a BLAST search of public sequence databases, the NOV33a protein was found to have homology to the proteins shown in the BLASTP data in Table 33D.
176TABLE 33DPublic BLASTP Results for NOV33aNOV33aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueAAL40734N-METHYL-D-ASPARTATE 1 . . . 11151110/1115 (99%)0.0RECEPTOR 3A-Homo sapiens 1 . . . 11151112/1115 (99%)(Human), 1115 aa.Q62800IONOTROPIC GLUTAMATE 1 . . . 11151032/1115 (92%)0.0RECEPTOR-Rattus norvegicus 1 . . . 11151083/1115 (96%)(Rat), 1115 aa.Q9R1M7N-METHYL-D-ASPARTATE 1 . . . 11151032/1135 (90%)0.0RECEPTOR SPLICE 1 . . . 11351083/1135 (94%)VARIANT NR3A-2-Rattusnorvegicus (Rat), 1135 aa.CAC69380SEQUENCE 7 FROM PATENT 95 . . . 1103 508/1047 (48%)0.0WO0144473-Homo sapiens 6 . . . 1007 680/1047 (64%)(Human), 1043 aa.Q91ZU9NMDA-TYPE GLUTAMATE112 . . . 1103 510/1001 (50%)0.0RECEPTOR SUBUNIT NR3B 34 . . . 980 669/1001 (65%)PRECURSOR-Mus musculus(Mouse), 1003 aa.


[0500] PFam analysis predicts that the NOV33a protein contains the domains shown in the Table 33E.
177TABLE 33EDomain Analysis of NOV33aIdentities/PfamNOV33a MatchSimilarities forExpectDomainRegionthe Matched RegionValuelig_chan: domain 1 of674 . . . 952 81/323 (25%)4e−951232/323 (72%)



Example 34

[0501] The NOV34 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 34A.
178TABLE 34ANOV34 Sequence AnalysisSEQ ID NO:1111253 bpNOV34a,CCCAGCGCCATGGGGGAGTGGGCGTTCCTGGGCTCGCTGCTGGACGCCGTGCAGCTGCCG59315-01 DNA SequenceAGTCGCCGCTCGTGGGCCGCCTCTGGCTGGTGGTCATGCTGATCTTCCGCATCCTGGTGCTGGCCACGGTGGGCGGCGCCGTGTTCGAGGACGAGCAAGAGGAGTTCGTGTGCAACACGCTGCAGCCGGGCTGTCGCCAGACCTGCTACGACCGCGCCTTCCCGGTCTCCCACTACCGCTTCTGGCTCTTCCACATCCTGCTGCTCTCCGCGCCCCCGGTGCTGTTCGTCGTCTACTCCATGCACCGGGCAGGCAAGGAGGCGGGCGGCGCTGAGGCGGCGGCGCAGTGCGCCCCCGGACTGCCCGAGGCCCAGTGCGCGCCGTGCGCCCTGCGCGCCCGCCGCGCGCGCCGCTGCTACCTGCTGAGCGTGGCGCTGCGCCTGCTGGCCGAGCTGACCTTCCTGGGCGGCCAGGCGCTGCTCTACGGCTTCCGCGTGGCCCCGCACTTCGCGTGCGCCGGTCCGCCCTGCCCGCACACGGTCGACTGCTTCGTGAGCCGCCCCACCGAGAAGACCGTCTTCGTGCTCTTCTATTTCGCGGTGGGGCTGCTGTCGGCGCTGCTCAGCGTAGCCGAGCTGGGCCACCTGCTCTGGAAGGGCCGCCCGCGCGCCGGGGAGCGTGACAACCGCTGCAACCGTGCACACGAAGAGGCGCAGAAGCTGCTCCCGCCGCCGCCGCCGCCACCTCCCCCACCGGCCCTGCCCTCCCGGCGCCCCGGCCCCGAGCCGTGCGCCCCGCCGGCCTATGCGCACCCGGCGCCGGCCAGCCTCCGCGAGTGCGGCAGCGGCCGCGGCAGGAATGCGCCAATGGCTCCCAGATGTGGACCCCACCGCTTAACCCCTTACCCCCCAGCCGCGCTCCCCCAAGGGCCTTCCAGCCTGAGCCCCGCCAACAGCAGGGAGCTCTGCCCAGGTGAGAACCAGCCCAGGACTGGAGTCAGCGCCAGCCCGCCCCTAGTGCCCACGGACACCTCCCAACCTAGATCCTACCTGTCTTCCTTCCTTGAGGCTGGAGGGGAAGGCTCATGGACACAAGAATGCAAGCATGCATGCACACAGCTACACTGCCTCCCATCCCCTCCCGCCGACGCTGCCAGGGTGCCCCTCCCTCGCTCCCCATCCTGGCAGGGCGGGCGGCGCAGAGCGCTCCACTCCGGATTCCCCACGCCCCCGAGCCGTTCGCAGGCTCGCACAAGORF Start: ATG at 10ORF Stop: AG at 1252SEQ ID NO:112414 aaMW at 44773.0 kDNOV34a,MGEWAFLGSLLDAVQLQSPLVGRLWLVVMLIFRILVLATVGGAVFEDEQEEFVCNTLQCG59315-01 Protein SequencePGCRQTCYDRAFPVSHYRFWLFHILLLSAPPVLFVVYSMHRAGKEAGGAEAAAQCAPGLPEAQCAPCALRARRARRCYLLSVALRLLAELTFLGGQALLYGFRVAPHFACAGPPCPHTVDCFVSRPTEKTVFVLFYFAVGLLSALLSVAELGHLLWKGRPRAGERDNRCNRAHEEAQKLLPPPPPPPPPPALPSRRPGPEPCAPPAYAHPAPASLRECGSGRGRNAPMAPRCGRHRLTPYPPAALPQGPSSLSPANSRELCPGENQPRTGVSASPPLVPTDTSQPRSYLSSFLEAGGEGSWTQECKHACTQLHCLPSPPADAARVPLPRSPSWQGGRRRALHSGFPTPPSRSQART


[0502] Further analysis of the NOV34a protein yielded the following properties shown in Table 34B.
179TABLE 34BProtein Sequence Properties NOV34aPSort0.6000 probability located in plasma membrane; 0.4000analysis:probability located in Golgi body; 0.3000 probabilitylocated in endoplasmic reticulum (membrane);0.0300 probability located in mitochondrial inner membraneSignalPLikely cleavage site between residues 39 and 40analysis:


[0503] A search of the NOV34a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 34C.
180TABLE 34CGeneseq Results for NOV34aNOV34aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAW49009Mouse alpha 3 connexin protein-1 . . . 296121/334 (36%)5e−52Mus sp, 417 aa. [WO9830677-A1,1 . . . 327169/334 (50%)16 JUL. 1998]AAW23968Connexin protein Cx40-Homo1 . . . 215 93/233 (39%)9e−46sapiens, 358 aa. [WO9802150-A1,1 . . . 232133/233 (56%)22 JAN. 1998]AAW23970Connexin protein Cx45-Homo4 . . . 212 93/252 (36%)3e−43sapiens, 396 aa. [WO9802150-A1,3 . . . 253137/252 (53%)22 JAN. 1998]AAW23969Connexin protein Cx43-Homo1 . . . 216 86/235 (36%)1e−42sapiens, 382 aa. [WO9802150-A1,1 . . . 235130/235 (54%)22 JAN. 1998]AAM93194Human polypeptide, SEQ ID NO:7 . . . 384129/409 (31%)8e−38[EP1130094-A2, 5 SEP. 2001]7 . . . 360169/409 (40%)


[0504] In a BLAST search of public sequence databases, the NOV34a protein was found to have homology to the proteins shown in the BLASTP data in Table 34D.
181TABLE 34DPublic BLASTP Results for NOV34aNOV34aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueQ91YD1CONNEXIN30.2-Mus musculus1 . . . 283228/283 (80%) e−129(Mouse), 278 aa.1 . . . 265240/283 (84%)I46053connexin44-bovine, 402 aa.1 . . . 397151/418 (36%)1e−621 . . . 396207/418 (49%)P41987Gap junction alpha-3 protein2 . . . 397150/417 (35%)4e−62(Connexin 44) (Cx44)-Bos1 . . . 395206/417 (48%)taurus (Bovine), 401 aa.AAA50954CONNEXIN44-Bos taurus1 . . . 398154/429 (35%)1e−60(Bovine), 407 aa.1 . . . 402214/429 (48%)Q9TU17GAP JUNCTION PROTEIN1 . . . 398147/415 (35%)1e−60(CONNEXIN)-Ovis aries1 . . . 408204/415 (48%)(Sheep), 413 aa.


[0505] PFam analysis predicts that the NOV34a protein contains the domains shown in the
182TABLE 34EDomain Analysis of NOV34aIdentities/PfamNOV34a MatchSimilarities forExpectDomainRegionthe Matched RegionValueDUF26: domain 1 of 1107 . . . 152 12/56 (21%)1.4 27/56 (48%)connexin: domain 1 of 1 . . . 212101/247 (41%)6.5e−751150/247 (61%)



Example 35

[0506] The NOV35 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 35A.
183TABLE 35ANOV35 Sequence AnalysisSEQ ID NO:113724 bpNOV35a,TAAATTCGCGGCCGCGTCGACCTTCCGCAGACTCAACTGAGAAGTCAGCCTCTGCGGCCG59203-01 DNA SequenceAGGCACCAGGAATCTGCCTTTTCAGTTCTGTCTCCGGCAGGCTTTGAGGATGAAGGCTGCGGGCATTCTGACCCTCATTGGCTGCCTGGTCACAGGCGCCGAGTCCAAAATCTACACTCGTTGCAAACTGGCAAAAATATTCTCGAGGGCTGGCCTGGACAATTACTGGGGCTTCAGCCTTGGAAACTGGATCTGCATGGCGTATTATGAGAGCGGCTACAACACCACAGCCCAGACGGTCCTGGATGACGGCAGCATCGACTACGGCATCTTCCAGATCAACAGCTTCGCGTGGTGCAGACGCGGAAAGCTGAAGGAGAACAACCACTGCCACGTCGCCTGCTCAGCCTTGGTCACTGATGACCTCACAGATGCGATTATCTGTGCCAAGAAAATTGTTAAAGAGACACAAGGAATGAACTATTGGCAAGGCTGGAAGAAACACTGTGAGGGGAGAGACCTGTCCGACTGGAAAAAAGACTGTGAGGTTTCCTAAACTGGAACTGGACCCAGGATGCTTTGCAGCAACGCCCTAGGGTTTGCAGTGAATGTCCAAATGCCTGTGTCATCTTGTCCCGTTTCCTCCCAATATTCCTTCTCAAACTTGGAGAGGGAAAATTAAGCTATACTTTTAAGAAAATAAATATTTCCATTTAAATGTCAAAAORF Start: ATG at 108ORF Stop: TAA at 552SEQ ID NO:114148 aaMW at 16655.9 kDNOV35a,MKAAGILTLIGCLVTGAESKIYTRCKLAKIFSRAGLDNYWGFSLGNWICMAYYESGYNCG59203-01 Protein SequenceTTAQTVLDDGSIDYGIFQINSFAWCRRGKLKENNHCHVACSALVTDDLTDAIICAKKIVKETQGMNYWQGWKKHCEGRDLSDWKKDCEVSSEQ ID NO:115453 bpNOV35b,CATTCTGACCCTCATTGGCTGCCTGGTCACAGGCGCCGAGTCCAAAATCTACACTCGTCG59203-02 DNA SequenceTGCAAACTGGCAAAAATATTCTCGAGGGCTGGCCTGGACAATTACTGGGGCTTCAGCCTTGGAAACTGGATCTGCATGGCGTATTATGAGAGCGGCTACAACACCACAGCCCAGACGGTCCTGGATGACGGCAGCATCGACTACGGCATCTTCCAGATCAACAGCTTCGCGTGGTGCAGACGCGGAAAGCTGAAGGAGAACAACCACTGCCACGTCGCCTGCTCAGCCTTGGTCACTGATGACCTCACAGATGCAATTATCTGTGCCAGGAAAATTGTTAAAGAGACACAAGGAATGAATTATTGGCAAGGCTGGAAGAAACATTGTGAGGGCAGAGACCTGTCCGACTGGAAAAAAGGCTGTGAGGTTTCCTAAACTGGAACTGGACCCAGGATORF Start: ATG at 134ORF Stop: TAA at 431SEQ ID NO:11699 aaMW at 11288.6 kDNOV35b,MAYYESGYNTTAQTVLDDGSIDYGIFQINSFAWCRRGKLKENNHCHVACSALVTDDLTCG59203-02 Protein SequenceDAIICARKIVKETQGMNYWQGWKKHCEGRDLSDWKKGCEVS


[0507] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 35B.
184TABLE 35BComparison of NOV35a against NOV35b.Identities/ProteinNOV35a Residues/Similarities forSequenceMatch Residuesthe Matched RegionNOV35b50 . . . 14897/99 (97%) 1 . . . 9998/99 (98%)


[0508] Further analysis of the NOV35a protein yielded the following properties shown in Table 35C.
185TABLE 35CProtein Sequence Properties NOV35aPsort0.3700 probability located in outside; 0.1697 probabilityanalysis:located in microbody (peroxisome); 0.1000 probability locatedin endoplasmic reticulum (membrane); 0.1000 probabilitylocated in endoplasmic reticulum (lumen)SignalPLikely cleavage site between residues 20 and 21analysis:


[0509] A search of the NOV35a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 35D.
186TABLE 35DGeneseq Results for NOV35aNOV35aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAY57399Human lysoenzyme LYC2 1 . . . 148143/148 (96%)3e−86polypeptide-Homo sapiens, 148 aa. 1 . . . 148147/148 (98%)[WO200012722-A1,9 MAR. 2000]AAU29169Human PRO polypeptide sequence 1 . . . 148143/148 (96%)6e−86#146-Homo sapiens, 148 aa. 1 . . . 148146/148 (98%)[WO200168848-A2,20 SEP. 2001]AAB66145Protein of the invention #57- 1 . . . 148143/148 (96%)6e−86Unidentified, 148 aa. 1 . . . 148146/148 (98%)[WO200078961-A1,28 DEC. 2000]AAY99396Human PRO1278 (UNQ648) 1 . . . 148143/148 (96%)6e−86amino acid sequence SEQ ID NO: 1 . . . 148146/148 (98%)203-Homo sapiens, 148 aa.[WO200012708-A2,9 MAR. 2000]AAY71109Human Hydrolase protein-7 1 . . . 148142/148 (95%)1e−85(HYDRL-7)-Homo sapiens, 19447 . . . 194146/148 (97%)aa. [WO200028045-A2,18 MAY 2000]


[0510] In a BLAST search of public sequence databases, the NOV35a protein was found to have homology to the proteins shown in the BLASTP data in Table 35E.
187TABLE 35EPublic BLASTP Results for NOV35aNOV35aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueQ96LF2BA14C22.1 (NOVEL PROTEIN 1 . . . 148148/148 (100%)7e−88SIMILAR TO LYSOZYME)- 1 . . . 148148/148 (100%)Homo sapiens (Human), 148 aa.Q9H1R9BA534G20.1.1 (NOVEL PROTEIN 1 . . . 148144/148 (97%)4e−86SIMILAR TO LYSOZYME C-1 1 . . . 148147/148 (99%)(1,4-BETA-N-ACYLMURAMIDASE C, EC3.2.1.17) (ISOFORM 1))-Homosapiens (Human), 148 aa.AAH21730HYPOTHETICAL 21.6 KDA 1 . . . 148143/148 (96%)2e−85PROTEIN-Homo sapiens47 . . . 194146/148 (98%)(Human), 194 aa.Q9CPX31700038F02RIK PROTEIN-Mus 1 . . . 148110/148 (74%)3e−66musculus (Mouse), 148 aa. 1 . . . 148127/148 (85%)Q9H1R8BA534G20.1.2 (NOVEL PROTEIN20 . . . 125104/106 (98%)1e−59SIMILAR TO LYSOZYME C-1 1 . . . 106106/106 (99%)(1,4-BETA-N-ACYLMURAMIDASE C, EC3.2.1.17) (ISOFORM 2))-Homosapiens (Human), 106 aa (fragment).


[0511] PFam analysis predicts that the NOV35a protein contains the domains shown in the Table 35F.
188TABLE 35FDomain Analysis of NOV35aIdentities/PfamNOV35a MatchSimilarities forExpectDomainRegionthe Matched RegionValuelys: domain 1 of 120 . . . 145 68/129 (53%)8e−58107/129 (83%)



Example 36

[0512] The NOV36 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 36A.
189TABLE 36ANOV36 Sequence AnalysisSEQ ID NO:117712 bpNOV36a,GCAGCTATTGCACTTAATCGCGGCTGCTAGCACCATGTCCCGCGTTTTGGTGCCTTGCCG58662-01 DNA SequenceCATGTGAAAGGCACCGTAGCCCTGCAGGTGGGGGACGTATGGACCTCCCAAGGCCGGCCTAGTGTGCTGGTCATTGATGTCACCTTCCCCTGTGTCACTCCGTTCGAGGGGATCACATTTAAGAATTATTACACAGCGTTTTTTGAGCATCCTGTCTGTCAGCACACCTCAGCACACACACCGGCCAAGTGGGTGACCTGCCTGTGGGACTACTGTCTGATGCCCGACCCACACAGTGAGGAGGGAGCCCAGGAGTATGTGTCGCTGTTCAAGCAACAGATACTGTGTGACATGGCCAGAATATCGGACCTACACCTGATTCTGCAGCAGCCATCACCACTGTGGCTGTCTTTCACAGTGGACGAGCTGCAGATCTATCAGCAGGGACCAAAGAGCCCCTCCATGATCTTCCCCAAGTGGCTCTCCCACCCAGTGCCCTGTGAGCAACCTGCACTCCTCCATGAGGGTCTCCCAGACCCCAGCAGGGTATCCTCTGAGGTGCAGCAGATGTGGGCACTGACAGAGATGATCCGGGCCAGTCACACCTCCGCGAGGATAGGCCACTTTGATGTAGATGGCTGTTATGACCTGAACTTACTCTCCTACACTTGAGTGGTGGCTCCTAGCCAAGATGTTGGCCTTTCTGTGCCCACTORF Start: ATG at 35ORF Stop: TGA at 668SEQ ID NO:118211 aaMW at 23932.3 kDNOV36a,MSRVLVPCHVKGTVALQVGDVWTSQCRPSVLVIDVTFPCVTPFEGITFKNYYTAFFEHCG58662-01 Protein SequencePVCQETSAHTPAKWVTCLWDYCLMPDPHSEEGAQEYVSLPKQQILCDMARISELHLILQQPSPLWLSFTVEELQIYQQGPKSPSMIFPKWLSHPVPCEQPALLHEGLPDPSRVSSEVQQMWALTEMIRASRTSARIGEFDVDGCYDLNLLSYTSEQ ID NO:119843 bpNOV36b,CTGGCCTGAAGCCATGTCCCGCGTTCTAGCACCATGTCCCGCGTCTAGCACCATGTCCCG58662-02 DNA SequenceCGCGTCTAGCACCATGTCCCGCGTTCTAGCACCATGTCCCGCGTTCTAGCACCATGTCCCGCGTTCTAGCACCATGTCCCGCGTTTTGGTGCCTTGCCATGTGAAAGGCTCCGTAGCCCTCCAGGTGGGCGACGTGCGGACCTCCCAAGGCCGGCCTGGCGTGCTGGTCATCGATGTCACCTTCCCCAGCGTCGCTCCCTTCGAGTTGCAGGAAATCACGTTTAAGAATTACTACACAGCTTTTTTGAGCATCCGTGTCCGTCAGTACACCTCAGCACACACACCTGCCAAGTGGGTGACCTGCCTTCGGGACTACTGCCTGATGCCTGACCCACACAGTGAAGAGGGAGCCCAGGAGTATGTATCGCTGTTCAAGCATCAGATGCTATGTGACATGGCTAGAATATCGGAGCTACGCCTGATTCTGCGGCAGCCATCACCACTGTGGCTGTCTTTCACAGTGGAGGAGCTGCAGATCTATCAGCAGGGACCAAAGAGCCCCTCCGTGACCTTTCCCAAGTGGCTCTCCCACCCAGTGCCCTGTGAGCAACCTGCACTCCTCCGTGAGGGTTTCCCAGACCCCAGCAGGGTATCCTCCGAGGTGCAGCAGATGTGGGCACTGACAGAGATGATCCGGGCCAGTCACACCTCCGCAAGGATCGGCCGCTTTGATGTGGATGGCTGTTATGACCTGACCTTGCTCTCCTACACTTGAATGGTTGCTCTTAGCCAAGATGTTGGCCTTTTTGTGGGCACAGAAAGGCCAACGCGGGACATGGTGCTAGORF Start: ATG at 132Stop: TGA at 771SEQ ID NO:120213 aaMW at 24222.6 kDNOV36b,MSRVLVPCHVKGSVALQVGDVRTSQGRPGVLVIDVTFPSVAPFELQEITFKNYYTAFLCG58662-02 Protein SequenceSIRVRQYTSAHTPAKWVTCLRDYCLMPDPHSEEGAQEYVLSFKHQMLCDMARISELRLILRQPSPLWLSFTVEELQIYQQGPKSPSVTFPKWLSHPVPCEQPALLREGFPDPSRVSSEVQQMWALTEMIRASHTSARIGRFDVDGCYDLTLLSYT


[0513] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 36B.
190TABLE 36BComparison of NOV36a against NOV36b.Identities/ProteinNOV36a Residues/Similarities forSequenceMatch Residuesthe Matched RegionNOV36b1 . . . 211188/213 (88%)1 . . . 213193/213 (90%)


[0514] Further analysis of the NOV36a protein yielded the following properties shown in Table 36C.
191TABLE 36CProtein Sequence Properties NOV36aPSort0.5666 probability located in microbody (peroxisome);analysis:0.4500 probability located in cytoplasm; 0.1562probability located in lysosome (lumen); 0.1000probability located in mitochondrial matrix spaceSignalPNo Known Signal Sequence Predictedanalysis:


[0515] A search of the NOV36a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 36D.
192TABLE 36DGeneseq Results for NOV36aNOV36aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAG04038Human secreted protein, SEQ ID1 . . . 10382/105 (78%)1e−39NO: 8119-Homo sapiens, 115 aa.1 . . . 10585/105 (80%)[EP1033401-A2, 6 SEP. 2000]


[0516] In a BLAST search of public sequence databases, the NOV36a protein was found to have homology to the proteins shown in the BLASTP data in Table 36E.
193TABLE 36EPublic BLASTP Results for NOV36aNOV36aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueQ9BSH3SIMILAR TO RIKEN CDNA1 . . . 211190/213 (89%) e−1071500032A17 GENE-Homo1 . . . 213195/213 (91%)sapiens (Human), 213 aa.Q9CQM01500032A17RIK PROTEIN-1 . . . 211174/213 (81%)4e−97Mus musculus (Mouse),1 . . . 213183/213 (85%)213 aa.


[0517] PFam analysis predicts that the NOV36a protein contains the domains shown in the Table 36F.
194TABLE 36FDomain Analysis of NOV36aIdentities/PfamNOV36aSimilarities forExpectDomainMatch Regionthe Matched RegionValueNo Significant Matches Found



Example 37

[0518] The NOV37 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 37A.
195TABLE 37ANOV37 Sequence AnalysisSEQ ID NO:121520 bpNOV37a,CATTTGCTGTCTCCTCTGCTCACCAGCAGCTGTACTGGAGCCACCCGCGAAAATTCGGCG58584-01 DNA SequenceCCAGGGTTCTCGCTCTTGTCGTGTCTGTTCAAACCGGCACGGTCTGATCCGGAAATATGGCCTCAATATGTGCCGCCAGTGTTTCCGTCAGTACGCGAAGGATATCGGTTTCATTAAGAAAGACCTGAGCTGTCTTCCTTGGCACTGCCTATGGAGGTGACACCCATCTCCTCCATCATGGCCATCCTGAGACCGCTCGCGAAGCCCAAGATCATCAAAAAGAGCACCAAGTTCACTGGGAACCAGTCAGACTGATATGTCAAAATTAAGGGTAACTGGTGGAAACACAGAGGTATTGACAACAGGGTTCATAGAAGGTTTGAGGGCCAGATCTATGCCCAACATTGGTTATGGGAGAAACAAAAAGACAAAGCACATACTGCCCAGTGGCTTCTGGAAGTTCCTCGTCCACAACGTTAAGGAGCTGGAAGTACTGCTGGTGAGCAGAGGAGACAGCAAATGORF Start: TTT at 3ORF Stop: TGA at 216SEQ ID NO:12271 aaMW at 8461.8 kDNOV37a,FAVSSAHQQLYWSHPRKFGQGSRSCRVCSNRHGLIRKYGLNMCRQCFRQYAKDIGFIKCG58584-01 Protein SequenceKDLSCLPWHCLWR


[0519] Further analysis of the NOV37a protein yielded the following properties shown in Table 37B.
196TABLE 37BProtein Sequence Properties NOV37aPSort0.6400 probability located in microbody (peroxisome);analysis:0.4500 probability located in cytoplasm; 0.1000probability located in mitochondrial matrixspace; 0.1000 probability located in lysosome (lumen)SignalPNo Known Signal Sequence Predictedanalysis:


[0520] A search of the NOV37a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 37C.
197TABLE 37CGeneseq Results for NOV37aNOV37aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAG76128Human colon cancer antigen 7 . . . 6046/54 (85%)4e−24protein SEQ ID NO: 6892-Homo 2 . . . 5548/54 (88%)sapiens, 80 aa. [WO200122920-A2, 5 APR. 2001]AAM79084Human protein SEQ ID NO 1746- 7 . . . 6039/54 (72%)2e−18Homo sapiens, 56 aa. 3 . . . 5643/54 (79%)[WO200157190-A2,9 AUG. 2001]AAG39921Arabidopsis thaliana protein 7 . . . 6340/57 (70%)2e−18fragment SEQ ID NO: 49464- 3 . . . 5845/57 (78%)Arabidopsis thaliana, 637 aa.[EP1033405-A2, 6 SEP. 2000]AAM80068Human protein SEQ ID NO 3714- 7 . . . 5838/52 (73%)5e−18Homo sapiens, 74 aa.22 . . . 7342/52 (80%)[WO200157190-A2,9 AUG. 2001]AAG34802Arabidopsis thaliana protein 7 . . . 5837/52 (71%)1e−17fragment SEQ ID NO: 42406- 3 . . . 5442/52 (80%)Arabidopsis thaliana, 56 aa.[EP1033405-A2, 6 SEP. 2000]


[0521] In a BLAST search of public sequence databases, the NOV37a protein was found to have homology to the proteins shown in the BLASTP data in Table 37D.
198TABLE 37DPublic BLASTP Results for NOV37aNOV37aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueBAB79485RIBOSOMAL PROTEIN S29- 7 . . . 6053/54 (98%)1e−27Homo sapiens (Human), 56 aa. 3 . . . 5653/54 (98%)P3005440S ribosomal protein S29-Homo 7 . . . 6053/54 (98%)1e−27sapiens (Human),, 55 aa. 2 . . . 5553/54 (98%)Q9OYP240S RIBOSOMAL PROTEIN S29- 7 . . . 6052/54 (96%)2e−27Ictalurus punctatus (Channel 3 . . . 5653/54 (97%)catfish), 56 aa.AAL62474RIBOSOMAL PROTEIN S29- 7 . . . 6041/54 (75%)6e−21Spodoptera frugiperda (Fall 3 . . . 5648/54 (87%)armyworm), 56 aa.Q9VH69CG8495 PROTEIN-Drosophila10 . . . 6041/51 (80%)3e−20melanogaster (Fruit fly), 56 aa. 6 . . . 5646/51 (89%)


[0522] PFam analysis predicts that the NOV37a protein contains the domains shown in the Table 37E.
199TABLE 37EDomain Analysis of NOV37aIdentities/PfamNOV37a MatchSimilarities forExpectDomainRegionthe Matched RegionValueRibosomal_S14:7 . . . 6117/60 (28%)7.5e−20domain 1 of 151/60 (85%)



Example 38

[0523] The NOV38 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 38A.
200TABLE 38ANOV38 Sequence AnalysisSEQ ID NO:1232039 bpNOV38a,GCAGCACACCTGCTCTGTGACTGACACTCTTGCAGAAGTGGGGCCACTTCAGGGACATCG58538-01 DNA SequenceGGACAAGGTGTTGTACCTGCTGTCACAGAGCCTGTTATCTGTTCAGAATGACCGAAGAAGCATGCCGAACACGGAGTCAGAAACGAGCGCTTGAACGGGACCCAACAGAGGACGATGTGGAGAGCAAGAAAATAAAAATGGAGAGAGGATTGTTGGCTTCAGATTTAAACACTGACGGAGACATGAGGGTGACACCTGAGCCCGCAGCAGGTCCAACCCAAGCATTGCTGAGGGCAACAGAGGCCACGGCCATGGCCATGGGCAGAGGCGAAGGGCTGGTGGGCGATGGGCCCGTGGACATGCGCACCTCACACAGTGACATGAAGTCCGAGAGGAGACCCCCCTCACCTGACGTGATTGTGCTCTCCGACAACGAGCAGCCCTCGAGCCCGAGAGTGAATGGGCTGACCACCGTGGCCTTGAAGGAGACTAGCACCGAGGCCCTCATGAAAAGCAGTCCTGAAGAACGAGAAAGGATGATCAAGCAGCTGAAGGAAGAATTGAGGTTAGAAGAAGCAAAACTCGTGTTGTTGAAAAAGTTGCGGCAGAGTCAAATACAAAAGGAAGCCACCGCCCAGAAGCCCACAGGTTCTGTTGGGAGCACCGTGACCACCCCTCCCCCGCTTGTTCGGGGCACTCAGAACATTCCTGCTGGCAAGCCATCACTCCAGACCTCTTCAGCTCGGATGCCCGGCAGTGTCATACCCCCGCCCCTGGTCCGAGGTGGGCAGCAGGCGTCCTCGAAGCTGGGGCCACAGGCGAGCTCACAGGTCGTCATGCCCCCACTCGTCAGGGGGGCTCAGCAAATCCACAGCATTAGGCAACATTCCAGCACAGGGCCACCGCCCCTCCTCCTGGCCCCCCGGGCGTCGGTGCCCAGTGTGCAGATTCAGGGACAGAGGATCATCCAGCAGGGCCTCATCCGCGTCGCCAATGTTCCCAACACCAGCCTGCTCGTCAACATCCCACAGCCCACCCCAGCATCACTGAAGGGGACAACAGCCACCTCCGCTCAGGCCAACTCCACCCCCACTAGTGTGGCCTCTGTGGTCACCTCTGCCGAGTCTCCAGCAAGCCGACAGGCGGCCGCCAAGCTGGCGCTGCGCAAACAGCTGGAGAAGACGCTACTCGAGATCCCCCCACCCAAGCCCCCAGCCCCAGAGATGAACTTCCTGCCCAGCGCCGCCAACAACGAGTTCATCTACCTGGTCGGCCTGGAGGAGGTGGTGCAGAACCTACTGGAGACACAAGCAGGCAGGATGTCGGCCGCCACTGTGCTGTCCCGGGAGCCCTACATGTGTGCACAGTGCAAGACGGACTTCACGTGCCGCTGGCGGGAGGAGAAGAGCGGCGCCATCATGTGTGAGAACTGCATGACAACCAACCAGAAGAAGGCGCTCAAGGTGGAGCACACCAGCCGGCTGAAGGCCGCCTTTGTGAAGGCGCTGCAGCAGGAACAGGAGATTGAGCAGCGGCTCCTGCAGCAGGGCACGGCCCCTGCACAGGCCAAGGCCGAGCCCACCGCTGCCCCACACCCCGTGCTGAAGCAGGCCTCCAGCCAGCTGTCCCGGGGTTCGGCCACGACGCCCCGAGGTGTCCTGCACACGTTCAGTCCGTCACCCAAACTGCAGAACTCAGCCTCGGCCACAGCCCTGGTCAGCAGGACCGGCAGACATTCTGAGAGAACCGTGAGCGCCGGCAAGGGCAGCGCCACCTCCAACTGGAAGAAGACGCCCCTCAGCACAGGCGGGACCCTTGCGTTTGTCAGCCCAAGCCTGGCGGTGCACAAGAGCTCCTCGGCCGTGGACCGCCAGCGAGAGTACCTCCTGGACATGATCCCACCCCGCTCCATCCCCCAGTCAGCCACGTGGAAATAGTGCGAGCCAGGCCCCGTGGAAGACGGGCTCCCTCCTCCCCCACCTGGCCCCTGGTCTAGAAGGACCCACTGCACCACCCTCCGCTGGCTCGGGAAGACACCGTGORF Start: ATG at 106ORF Stop: TAG at 1933SEQ ID NO:124609 aaMW at 65295.8 kDNOV38a,MTEEACRTRSQKRALERDPTEDDVESKKIKMERGLLASDLNTDGDMRVTPEPGAGPTQCG58538-01 Protein SequenceGLLRATEATAMAMGRGEGLVGDGPVDMRTSHSDMKSERRPPSPDVIVLSDNSQPSSPRVNGLTTVAIKETSTEALMKSSPEERERNIKQLKEELRLEEAKLVLLKKLRQSQIQKEATAQKPTGSVGSTVTTPPPLVRGTQNIPAGKPSLQTSSARMPGSVIPPPLVRGGQQASSKLGPQASSQVVMPPLVRGAQQIHSIRQHSSTGPPPLLLAPRASVPSVQIQGQRIIQQGLIRVANVPNTSLLVNIPQPTPASLKGTTATSAQANSTPTSVASVVTSAESPASRQAAAKLALRKQLEKTLLEIPPPKPPAPEMNFLPSAANNEFIYLVGLEEVVQNLLETQAGRMSAATVLSREPYMCAQCKTDFTCRWREEKSGAIMCENCMTTNQKKALKVEHTSRLKAAEVKALQQEQEIEQRLLQQGTAFAQAKAEPTAAPHPVLKQASSQLSRGSATTPRGVLHTFSPSPKLQNSASATALVSRTGRHSERTVSAGKGSATSNWKKTPLSTGGTLAFVSPSLAVHKSSSAVDRQREYLLDMIPPRSIPQSATWK


[0524] Further analysis of the NOV38a protein yielded the following properties shown in Table 38B.
201TABLE 38BProtein Sequence Properties NOV38aPSort0.4404 probability located in mitochondrial matrix space;analysis:0.3000 probability located in microbody (peroxisome); 0.1257probability located in mitochondrial inner membrane; 0.1257probability located in mitochondrial intermembrane spaceSignalPNo Known Signal Sequence Predictedanalysis:


[0525] A search of the NOV38a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 38C.
202TABLE 38CGeneseq Results for NOV38aNOV38aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAM00991Human bone marrow protein, SEQ 1 . . . 471217/504 (43%)2e−87ID NO: 492-Homo sapiens, 502 4 . . . 473290/504 (57%)aa. [WO200153453-A2,26 JUL. 2001]AAM00944Human bone marrow protein, SEQ 1 . . . 471217/504 (43%)2e−87ID NO: 420-Homo sapiens, 546 48 . . . 517290/504 (57%)aa. [WO200153453-A2,26 JUL. 2001]AAM00831Human bone marrow protein, SEQ 1 . . . 197 84/217 (38%)1e−23ID NO: 194-Homo sapiens, 266 47 . . . 262110/217 (49%)aa. [WO200153453-A2,26 JUL. 2001]AAM85818Human immune/haematopoietic417 . . . 471 41/55 (74%)7e−19antigen SEQ ID NO: 13411-Homo 1 . . . 55 49/55 (88%)sapiens, 84 aa. [WO200157182-A2, 9 AUG. 2001]


[0526] In a BLAST search of public sequence databases, the NOV38a protein was found to have homology to the proteins shown in the BLASTP data in Table 38D.
203TABLE 38DPublic BLASTP Results for NOV38aNOV38aProteinProtein/Residues/Identities/AccessionOrganism/MatchSimilarities forExpectNumberLengthResiduesthe Matched PortionValueNo Significant Matches Found


[0527] PFam analysis predicts that the NOV38a protein contains the domains shown in the Table 38E.
204TABLE 38EDomain Analysis of NOV38aIdentities/PfamNOV38a MatchSimilarities forExpectDomainRegionthe Matched RegionValueGATA: domain 1 of 1414 . . . 45312/43 (28%)1.117/43 (40%)



Example 39

[0528] The NOV39 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 39A.
205TABLE 39ANOV39 Sequence AnalysisSEQ ID NO:1251421 bpNOV39a,ACCATTTCAGAGATGTCTTCCAGAAGTACCAAAGATTTAATTAAAAGTAAGTGGGGATCG59371-01 DNA SequenceCGAAGCCTAGTAACTCCAAATCCGAAACTACATTAGAAAAATTAAAGGGAGAAATTGCACACTTAAAGACATCAGTGGATGAAATCACAAGTGGGAAAGGAAAGCTGACTGATAAAGAGAGACACAGACTTTTGGAGAAAATTCGAGTCCTTGAGGCTGAGAAGGAGAAGAATGCTTATCAACTCACAGAGAAGGACAAAGAAATACAGCGACTGAGAGACCAACTGAAGGCCAGATATAGTACTACCACATTGCTTGAACAGCTGGAAGAGACAACGAGAGAAGGAGAAAGGAGGGAGCAGGTGTTGAAAGCCTTATCTGAAGAGAAAGACGTATTGAAACAACAGTTGTCTGCTGCAACCTCACGAATTGCTGAACTTGAAAGCAAAACCAATACACTCCGTTTATCACAGACTGTGGCTCCAAACTGCTTCAACTCATCAATAAATAATATTCATGAAATGGAAATACAGCTGAAAGATGCTCTGGAGAAAAATCAGCAGTGGCTCGTGTATGATCAGCAGCGGGAAGTCTATGTAAAAGGACTTTTAGCAAAGATCTTTGAGTTGGAAAAGAAAACGGAAACAGCTGCTCATTCACTCCCACAGCAGACAAAAAAGCCTGAATCAGAAGGTTATCTTCAAGAAGAGAAGCAGAAATGTTACAACGATCTCTTGGCAACTGCAAAAAAAGATCTTGAGGTTGAACGACAAACCATAACTCAGCTGAGTTTTGAACTGAGTGAATTTCGAAGAAAATATGAAGAAACCCAAAAAGAAGTTCACAATTTAAATCAGCTGTTGTATTCACAAAGAAGGGCAGATGTGCAACATCTGGAAGATGATAGGCATAAAACAGAGAAGATACAAAAACTCAGGGAAGAGAATGATATTGCTAGGGGAAAACTTGAAGAAGAGAAGAAGAGATCCGAAGAGCTCTTATCTCAGGTCCAGTCTCTTTACACATCTCTGCTAAACCAGCAAGAAGAACAAACAAGGGTAGCTCTGTTGGAACAACAGATGCAGGCATGTACTTTAGACTTTGAAAATGAAAAACTCGACCGTCAACATGTGCAGCATCAATTGCATGTAATTCTTAAGGAGCTCCGAAAAGCAAGAAAAAATATAACACAGTTGGAATCCTTGAAACAGCTTCATGAGTTTGCCATCACAGAGCCATTAGTCACTTTCCAAGGAGAGACTGAAAACAGAGAAAAAGTTGCCGCCTCACCAAAAAGTCCCACTGCTGCACTCAATGGAAGCCTGGTGGAATGTCCCAAGTGCAATATACAGTATCCAGCCACTGAGCATCGCGATCTGCTTGTCCATGTGGAATACTGTTCAAAGTAGCAAAATAAGTATTTORF Start: ATG at 13ORF Stop: TAG at 1405SEQ ID NO:126464 aaMW at 54045.6 kDNOV39a,MSSRSTKDLIKSKWGSKPSNSKSETTLEKLKGEIAHLKTSVDEITSGKGKLTDKERHRCG59371-01 Protein SequenceLLEKIRVLEAEKEKNAYQLTEKDKEIQRLRDQLKARYSTTTLLEQLEETTREGERREQVLKALSEEKDVLKQQLSAATSRIAELESKTNTLRLSQTVAPNCFNSSINNIHEMEIQLKDALEKNQQWLVYDQQREVYVKGLLAKTFELEKKTETAAHSLPQQTKKPSSEGYLQEEKQKCYNDLLASAKKDLEVERQTITQLSFELSEFRRKYEETQKEVHNLNQLLYSQRRADVQHLEDDRHKTEKIQKLREENDIARGKLEEEKKRSEELLSQVQSLYTSLLKQQEEQTRVALLEQQAQACTLDFENEKLDRQHVQHQLNVILKELRKARKNITQLESLKQLHEFAITEPLVTFQGETENREKVAASPKSPTAALNGSLVECPKCNIQYPATEHRDLLVHVEYCSK


[0529] Further analysis of the NOV39a protein yielded the following properties shown in Table 39B.
206TABLE 39BProtein Sequence Properties NOV39aPSort0.4500 probability located in cytoplasm; 0.3000analysis:probability located in microbody (peroxisome);0.1000 probability located in mitochondrial matrixspace; 0.1000 probability located in lysosome (lumen)SignalPNo Known Signal Sequence Predictedanalysis:


[0530] A search of the NOV39a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 39C.
207TABLE 39CGeneseq Results for NOV39aNOV39aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAB92925Human protein sequence SEQ ID170 . . . 392222/223 (99%) e−122NO: 11576-Homo sapiens, 231 aa. 1 . . . 223222/223 (99%)[EP1074617-A2, 7 FEB. 2001]AAG75490Human colon cancer antigen 1 . . . 67 64/67 (95%)1e−28protein SEQ ID NO: 6254-Homo 99 . . . 165 64/67 (95%)sapiens, 165 aa. [WO200122920-A2, 5 APR. 2001]AAM78520Human protein SEQ ID NO 1182- 6 . . . 394 96/421 (22%)3e−12Homo sapiens, 990 aa.515 . . . 929182/421 (42%)[WO200157190-A2,9 AUG. 2001]AAM41000Human polypeptide SEQ ID NO 70 . . . 420 90/384 (23%)3e−125931-Homo sapiens, 1988 aa.852 . . . 1203161/384 (41%)[WO200153312-A1,26 JUL. 2001]AAM40999Human polypeptide SEQ ID NO 70 . . . 420 90/384 (23%)3e−125930-Homo sapiens, 1988 aa.852 . . . 1203161/384 (41%)[WO200153312-A1,26 JUL. 2001]


[0531] In a BLAST search of public sequence databases, the NOV39a protein was found to have homology to the proteins shown in the BLASTP data in Table 39D.
208TABLE 39DPublic BLASTP Results for NOV39aNOV39aIdentities/ProteinResidues/Similarities forAccessionMatchthe MatchedExpectNumberProtein/Organism/LengthResiduesPortionValueQ96H32SIMILAR TO RIKEN CDNA1 . . . 464458/464 (98%)0.01200008O12 GENE - Homo1 . . . 464458/464 (98%)sapiens (Human), 464 aa.Q9DBZ81200008O12RIK PROTEIN - 1 . . . 464348/464 (75%)0.0Mus musculus (Mouse), 462 aa.1 . . . 462401/464 (86%)Q9NVS7CDNA FLJ10540 FIS, CLONE170 . . . 392 222/223 (99%) e−122NT2RP2001245 - Homo sapiens1 . . . 223222/223 (99%)(Human), 231 aa.Q9CZP82700032M20RIK PROTEIN -1 . . . 176121/176 (68%)3e−63Mus musculus (Mouse), 189 aa.1 . . . 176150/176 (84%)Q9VJE5CLIP-190 PROTEIN - Drosophila4 . . . 439108/461 (23%)2e−16melanogaster (Fruit fly), 1690 aa.675 . . . 1118 203/461 (43%)


[0532] PFam analysis predicts that the NOV39a protein contains the domains shown in the Table 39E.
209TABLE 39EIdentities/NOV39aSimilaritiesExpectPfam DomainMatch Regionfor the Matched RegionValueNo Significant Matches Found


[0533] Table 39E. Domain Analysis of NOV39a Identities Pfam Domain NOV39a Match Region Similarities Expect Value for the Matched Region No Significant Matches Found



Example 40

[0534] The NOV40 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 40A.
210TABLE 40ANOV40 Sequence AnalysisSEQ ID NO:1273955 bpNOV40a,TGCACCCTCGCTGCCTCCTTTCCTCCATGCTGCCTGGATCTGGCGAGCTGGGGTGATTCG59346.01 DNA SequenceAATTGGCTATGATGATGAACGTCCCCGGCGGAGGAGCGGCCGCGGTGATGATGACGGGCTACAATAATGGTCGCTGTCCCCGGAATTCTCTCTACAGTGACTGCATTATTGAGGAGAAGACGGTGGTCCTGCAGAAAAAAGACAATGAGGGCTTTGGATTCGTGCTTCGAGGGGCCAAAGCTGACACACCCATTGAAGAATTCACACCAACACCGGCTTTCCCAGCCCTACAGTACCTGGAGTCCGTGGATGAAGGTGGGGTGGCGTGGCAAGCCCGACTAAGGACCGGGGACTTCTTGATTGAGGTTAACAATGAGAATGTTGTCAAAGTCGGCCACAGGCAGGTGGTGAACATGATCCGGCAGGGAGGGAATCACCTGGTCCTTAAGGTGGTCACGGTGACCAGGAATCTGGACCCCGACGACACCGCCAGGAAGAAAGCTCCCCCGCCTCCAAAGCGGGCACCGACCACAGCCCTCACCCTGCGCTCCAAGTCCATGACCTCGGAGCTGGAGGAGCTCGATAAACCCGAGGAGATAGTCCCGGCCTCCAAGCCCTCCCGCGCTGCTGAGAACATGGCTGTGGAACCGAGGGTGGCGACCATCAAGCAGCGGCCCAGCAGCCGGTGCTTCCCGGCGGGCTCAGACATGAACGTGAGTGGCCGTACCTTGGGACCACGAGGGCGGGGGCCGACGGTGCCCCCTAGGCTCTCTGGTTTGCAGTCTGTGTACGAACGCCAAGGAATCGCCGTGATGACGCCCACTGTTCCTGGGAGCCCAAAAGCCCCGTTTCTGGGCATCCCTCGAGGTACGATGCGAAGGCAGAAATCAATAGGAATAACAGAGGAAGAGCGGCAGTTTCTGGCTCCTCCAATGCTGAAGTTCACCAGAAGCCTGTCCATGCCGGACACCTCTGAGGACATCCCCCCTCCACCGCAGTCTGTGCCCCCGTCCCCACCACCACCTTCCCCAACCACTTACAACTGCCCCAAGTCCCCAACTCCAAGAGTCTACGGGACGATTAAGCCTGCGTTCAATCAGAATTCTGCCGCCAAGGTGTCCCCCGCCACCAGGTCCGACACCGTGGCCACCATGATGAGGGAGAAGGGGATGTACTTCAGGAGAGAGCTGGACCGCTACTCCTTGGACTCTGAAGACCTCTACAGTCGGAATGCCGGCCCGCAAGCCAACTTCCGCAACAAGAGAGGCCAGATGCCAGAAAACCCATACTCAGACGTGGGGAAGATCGCCAGCAAAGCCGTCTACGTCCCCGCCAAGCCCGCCAGGCGGAAGGGGATGCTGGTGAAGCAGTCCAACGTGGAGGACAGCCCCGAGAAGACGTGCTCCATCCCTATCCCGACCATCATCGTGAAGGAGCCGTCCACCAGCAGCAGCGGCAAGAGCAGCCAGGGCAGCAGCATGGAGATCGACCCCCAGGCCCCGGAGCCACCGAGCCAGCTGCGGCCTGACGAAAGCCTCACCGTCAGCAGCCCCTTTGCCGCCGCCATCGCCGGAGCCGTCCGCGACCGTGAGAAGCGGCTGGAAGCCAGGAGGAACTCCCCGGCCTTCCTCTCCACAGACCTGGGGGATGAGGATGTGGGCCTGGGGCCACCCGCCCCCAGGACGCGGCCCTCCATGTTCCCCGAGGAGGGGGATTTTGCTGACGAGGACAGCGCTGAGCAGCTGTCATCCCCCATGCCGAGTGCCACGCCCAGGGAGCCCGAAAACCATTTCGTGGGTGGCGCCGAGGCCAGTGCTCCGGGTGAGGCTGGGAGGCCGCTGAATTCCACGTCCAAAGCCCAGGGGCCCGAGAGCAGCCCAGCAGTGCCCTCCGCGAGCAGCGGCACAGCCGGCCCCGGGAATTATGTCCACCCACTCACAGGGCGGCTGCTTGATCCCAGCTCCCCGCTGGCCCTGGCACTCTCCGCAAGGGACCCAGCCATGAAGGAGTCTCAACAGGGACCCAAAGGGGAGGCCCCCAAGGCCGACCTCAACAAACCTCTTTACATTGATACCAAAATGCGGCCCAGCCTGGATGCCGGCTTCCCTACGGTCACCAGGCAGAACACCCGGGGACCCCTGAGGCGGCAGGAGACGGAGAACAAGTACGAGACCGACCTGGGCCGAGACCGGAAAGGCGATGACAAGAAGAACATGCTGATCGACATCATGGACACGTCCCAGCAGAAGTCGGCTGGCCTGCTGATGGTGCACACCGTGGACGCCACTAAGCTGGACAACGCCCTGCAGGAAGAGGACGAGAAGGCAGAGGTGGAGATGAAGCCAGACAGCTCGCCGTCCGAGGTGCCAGAAGGTGTTTCCGAAACCGAAGGTGCTTTACAGATCTCCGCTGCCCCCGAGCCCACCACCGTGCCCGGCAGAACCATCGTCGCGGTGGGCTCCATGGAAGAGGCGGTGATTTTGCCATTCCGCATCCCTCCTCCCCCTCTGGCATCCGTGGACTTGGATGAGGATTTTATTTTTACAGAGCCATTGCCTCCTCCCCTGGAATTTGCAAATAGTTTTGATATCCCCGATGACCGGGCAGCTTCTGTCCCGGCTCTCTCAGACTTAGTGAAGCAGAACAAAAGCGACACCCCTCAGTCCCCTTCGTTGAACTCCAGCCAACCAACCAACTCTGCAGACAGCAAGAAGCCAGCCAGTCTTTCAAACTGTCTGCCTGCCTCATTCCTGCCACCCCCTGAAAGCTTTGACGCCGTCGCCGACTCTGGGATCGAGGAGGTGGACAGCCGGAGTAGCAGCGACCACCACCTCGAGACGACCAGCACTATCTCCACCGTGTCTAGCATCTCCACCCTGTCTTCCGAAGGTGGAGAGAATGTGGACACCTGCACAGTCTATGCAGATGGGCAAGCATTTATGGTTGACAAACCCCCAGTACCTCCTAAGCCAAAAATGAAGCCCATCATTCACAAAAGCAATGCACTTTATCAAGACGCGCTCGTGGAAGAAGATGTAGATAGCTTTGTTATCCCCCCGCCCGCTCCCCCGCCCCCGCCGGGCAGTGCCCAGCCTGGGATGGCCAAGGTTCTCCAGCCAAGGACCTCCAAGTTGTGGGGCGACGTCACAGAGATCAAAAGCCCGATTCTCTCAGGCCCAAAGGCAAACGTTATTAGTGAATTGAACTCTATCCTACAGCAAATGAACCGAGAGAAATTGGCAAAGCCGGGGGAAGGACTGGATTCACCAATGGGAGCCAAGTCCGCCAGCCTCGCTCCAAGAAGCCCGGAGATCATGAGCACCATCTCAGGTACACGGAGCACGACGGTCACCTTCACTGTTCGCCCCGGCACCTCCCAGCCCATCACCCTGCAGAGCCGGCCCCCCGACTATGAAAGCAGGACCTCAGGAACAAGACGTGCCCCAAGCCCTGTGGTCTCGCCAACACAGATGAACAAAGAGACCCTGCCCGCCCCCCTGTCTGCTGCCACCGCCTCTCCTTCTCCCGCTCTCTCAGATGTCTTTAGCCTTCCAAGCCAGCCCCCTTCTGGGGATCTATTTGGCTTGAACCCAGCGGGACGCAGTAGGTCGCCATCCCCCTCGATACTGCAACAGCCAATCTCAAATAAGCCTTTTACAACTAAACCTGTCCACCTGTGGACTAAACCAGATGTGGCCGATTGGCTGGAAAGTCTAAACTTGGGTGAACATAAAGAGGCCTTCATGGACAATGAGATCGATGGCAGTCACTTACCAAACCTGCAGAAGGAGGACCTCATCGATCTTGGGGTAACTCGAGTCGGGCACAGAATGAACATAGAAAGGGCTTTGAAACAGCTGCTGGACAGATAAGGACGGCTGCTCTCCACCTCGCAGACTGCTCTTGTTATAAGTAGAGATGGGCTCGTGCTGAAACATCTGAATGCCAAGCGAAGTCORF Start: ATG at 67ORF Stop: TAA at 3868SEQ ID NO:1281267 aaMW at 136108.7 kDNOV40a,MMMNVPGGGAAAVMNTGYNNGRCPRNSLYSDCIIEEKTVVLQKKDNEGFGFVLRGAKACG59346-01 ProteinSequenceDTPIEEFTPTPAFPALQYLESVDEGGVAWQAGLRTGDFLIEVNNENVVKVGHRQVVNMIRQGGNHLVLKVVTVTRNLDPDDTARKKAPPPPKRAPTTALTLRSKSMTSELEELDKPEEIVPASKPSRAAENMAVEPRVATIKQRPSSRCFPAGSDNNVSGRTLGPRGRGPTVPPRLSGLQSVYERQGIAVMTPTVPGSPKAPFLGIPRGTMRRQKSTGTTEEERQFLAPPMLKFTRSLSMPDTSEDIPPPPQSVPPSPFPPSPTTYNCPKSPTPRVYGTIKPAFNQNSAAKVSPATRSDTVATMMREKGMYFRRELDRYSLDSEDLYSRNAGPQANFRNKRGQMPENPYSEVGKIASKAVYVPAKPARRKGMLVKQSNVEDSPEKTCSIPTPTIIVKEPSTSSSGKSSQGSSMEIDPQAPEPPSQLRPDESLTVSSPFAAAIAGAVRDREKRLEARRNSPAFLSTDLGDEDVGLGPPAPRTRPSMFPEEGDFADEDSAEQLSSPMPSATPREPENHFVGGAEASAPGEAGRPLNSTSKAQGPESSPAVPSASSGTAGPGNYVHPLTGRLLDPSSPLALALSARDRAMKESQQGPKGEAPKADLNKPLYIDTKMRPSLDAGFPTVTRQNTRGPLRRQETENKYETDLGRDRKGDDKKNNLIDIMDTSQQKSAGLLMVHTVDATKLDNALQEEDEKAEVEMKPDSSPSEVPEGVSETEGALQISAAPEPTTVPGRTIVAVGSMEEAVILPFRIPPPPLASVDLDEDFIFTEPLPPPLEFANSFDIPDDRAASVPALSDLVKQRKSDTPQSPSLNSSQPTNSADSKKPASLSNCLPASFLPPPESFDAVADSGIEEVDSRSSSDHHLETTSTISTVSSISTLSSEGGENVDTCTVYADGQAFMVDKPPVPPKPKNKPIIHKSNALYQDALVEEDVDSFVIPPPAPPPPPGSAQPGMAKVLQPRTSKLWGDVTEIKSPILSGPKANVISELNSILQQMNREKLAKPGEGLDSPMGAKSASLAPRSPEIMSTISGTRSTTVTFTVRPGTSQPITLQSRPPDYESRTSGTRRAPSPVVSPTEMNKETLPAPLSAATASPSPALSDVFSLPSQPPSGDLFGLNPAGRSRSPSPSILQQPISNKPFTTKPVHLWTKPDVADWLESLNLGEHKEAFMDNEIDGSHLPNLQKEDLIDLGVTRVGHRMNIERALKQLLDR


[0535] Further analysis of the NOV40a protein yielded the following properties shown in Table 40B.
211TABLE 40BProtein Sequence Properties NOV40aPSort0.4500 probability located in cytoplasm; 0.3000 probabilityanalysis:located in microbody (peroxisome); 0.1000 probabilitylocated in mitochondrial matrix space; 0.1000 probabilitylocated in lysosome (lumen)SignalPNo Known Signal Sequence Predictedanalysis:


[0536] A search of the NOV40a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 40C.
212TABLE 40CGeneseq Results for NOV40aNOV40aIdentities/Residues/Similarities forGeneseqProtein/Organism/LengthMatchthe MatchedExpectIdentifier[Patent #, Data]ResiduesRegionValueAAM79240Human protein SEQ ID NO 1902 -14 . . . 12671231/1271(96%)0.0Homo sapiens, 1248 aa. 1 . . . 12481231/1271(96%)[WO200157190-A2, 9 AUG 2001]AAB31518Amino acid sequence of the rat30 . . . 12671078/1255(85%)0.0Shank2 polypeptide - Rattus sp,240 . . . 1470 1132/1255(89%)1470 aa. [WO200078921-A2,28 DEC 2000]AAM80224Human protein SEQ ID NO 3870 -172 . . . 1267 1071/1103(97%)0.0Homo sapiens, 1161 aa.82 . . . 11611071/1103(97%)[WO200157190-A2, 9 AUG2001]AAB31517Amino acid sequence of the rat18 . . . 1264496/1349(36%)0.0Shank3a polypeptide - Rattus sp,550 . . . 1737 673/1349(49%)1740 aa. [WO200078921-A2,28 DEC 2000]AAY83017Rat shank 3a - Rattus rattus, 174018 . . . 1264496/1349(36%)0.0aa. [WO200011204-A2,550 . . . 1737 673/1349(49%)2 MAR 2000]


[0537] In a BLAST search of public sequence databases, the NOV40a protein was found to have homology to the proteins shown in the BLASTP data in Table 40D.
213TABLE 40DPublic BLASTP Results for NOV40aNOV40aIdentities/ProteinResidues/Similarities forAccessionMatchthe MatchedExpectNumberProtein/Organism/LengthResiduesPortionValueQ9UPX8KIAA1022 PROTEIN - Homo124 . . . 1267 1121/1154 (97%)0.0sapiens (Human), 1131 aa1 . . . 11311121/1154 (97%)(fragment).Q9QX93PROLINE RICH SYNAPSE2 . . . 12671103/1276 (86%)0.0ASSOCIATED PROTEIN 1 -1 . . . 12521158/1276 (90%)Rattus norvegicus (Rat), 1252 aa.O70470CORTACTIN-BINDING2 . . . 12671102/1276 (86%)0.0PROTEIN 1 - Rattus norvegicus1 . . . 12521158/1276 (90%)(Rat), 1252 aa.Q9WUV9PROLINE RICH SYNAPSE2 . . . 12671103/1283 (85%)0.0ASSOCIATED PROTEIN 1 -1 . . . 12591158/1283 (89%)Rattus norvegicus (Rat), 1259 aa.Q9WUW0PROLINE RICH SYNAPSE2 . . . 12671095/1276 (85%)0.0ASSOCIATED PROTEIN 1 -1 . . . 12501151/1276 (89%)Rattus norvegicus (Rat), 1250 aa.


[0538] PFam analysis predicts that the NOV40a protein contains the domains shown in the Table 40E.
214TABLE 40EDomain Analysis of NOV40aIdentities/SimilaritiesNOV40afor theExpectPfam DomainMatch RegionMatched RegionValuePDZ: domain 1 of 1 38 . . . 13123/97 (24%)  1e−0770/97 (72%)SAM: domain 1 of 11202 . . . 126527/68 (40%)9.8e−2253/68 (78%)



Example 41

[0539] The NOV41 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 41A.
215TABLE 41ANOV41 Sequence AnalysisSEQ ID NO:1292069 bpNOV41a,GGACACTGACATGGACTGAAGGAGTAGAAAGCACTATAAATGTCTTTCCTTATCTGTGCG57814-01 DNA SequenceTGTACTCTTATCTCACTGTTCTATTTTTTCTCCTCATTTATATTAACTCTTTCTTACCTTTTTTTCTGAACTTCTAGGCCTTCTCTTTCCAGAACTGGTGGAAGACAAATGAAACGGCCAAGATGGTAAGAAACAAGCCGCATTTCTCCTTGGGGAGACTGATAATTTAAAAGGTTTGTTGTGTCAGAAACATTCCCAGCTTCATCACCAACCCTTTCCTTCCACCTCTGCCCACTGGAGACCACTTACATCCCGAAGCGGACGCGGCAGCTGAAGTCAGGAAACCATGCATCACATTAGCAGGAGCCAACTGCAGACTTTAAACTCCGTTCAACATGTGGATGCGGCAGAGAAATGACCTGTCCAGACAAGCCGGGGCAGCTCATAAACTGGTTCATCTGCTCCCTGTGCGTCCCGCGGGTGCGTAAGCTCTGGAGCAGCCGGCGTCCAAGGACCCGGAGAAACCTTCTGCTGGGCACTGCGTGTGCCATCTACTTGGGCTTCCTGGTGAGCCAGGTGGGGAGGGCCTCTCTCCAGCATGGACAGGCGGCTGAGAAGGGGCCACATCGCAGCCGCGACACCGCCGAGCCATCCTTCCCTGAGATACCCCTGGATGGTACCCTGGCCCCTCCAGAGTCCCAGGGCAATGGGTCCACTCTGCAGCCCAATGTGGTGTACATTACCCTACGCTCCGAGCGCAGCAAGCCGGCCAATATCCGTGGCACCGTGAAGCCCAAGCGCAGGAAAAAGCATGCAGTGGCATCGGCTGCCCCAGGGCAGGAGGCTTTGGTCGGACCATCCCTTCAGCCGCAGGAAGCGGCAAGGGAAGCTGATGCTGTAGCACCTGGGTACGCTCAGGGAGCAAACCTGGTTAAGATTGGAGAGCGACCCTGGAGGTTGGTGCGGGGTCCGGGAGTGCGAGCCGGGGGCCCAGACTTCCTGCAGCCCAGCTCCAGGGAGAGCAACATTAGGATCTACAGCGAGAGCGCCCCCTCCTGGCTGAGCAAAGATGACATCCGAAGAATGCGACTCTTGGCGGACAGCGCAGTGGCAGGGCTCCGGCCTGTGTCCTCTAGGAGCGGAGCCCGTTTGCTGGTGCTGGAGGGGGGCGCACCTGGCGCTGTGCTCCGCTGTGGCCCTAGCCCCTGTGGGCTTCTCAAGCAGCCCTTGGACATGAGTGAGGTGTTTGCCTTCCACCTAGACAGGATCCTGGGGCTCAACAGGACCCTGCCGTCTGTGAGCAGGAAAGCAGAGTTCATCCAAGATGCCCGCCCATGCCCCATCATTCTTTGGGATGCATCTTTATCTTCAGCAAGTAATGACACCCATTCTTCTGTTAAGCTCACCTGGGGAACTTATCAGCAGTTGCTGAAACAGAAATGCTGGCAGAATGGCCGAGTACCCAAGCCTGAATCAGGTTGTACTGAAATACATCATCATGAGTGGTCCAAGATGGCACTCTTTGATTTTTTGTTACAGATTTATAATCGCTTAGATACAAATTGCTGTGGATTCAGACCTCGCAAGGAAGATGCCTGTGTACAGAATGGATTGAGGCCAAAATGTGATGACCAAGGTTCTGCGGCTCTAGCACACATTATCCAGCGAAAGCATGACCCAAGGCATTTGGTTTTTATAGACAACAAGGGTTTCTTTGACAGGAGTGAAGATAACTTAAACTTCAAATTGTTAGAAGGCATCAAAGAGTTTCCAGCTTCTGCAGTTTCTGTTTTGAAGAGCCAGCACTTACGGCAGAAACTTCTTCAGTCTCTGTTTCTTGATAAAGTGTATTGGGAAAGTCAAGGAGGTAGACAAGGAATTGAAAAGCTTATCGATGTAATAGAACACAGAGCCAAAATTCTTATCACCTATATCAATGCACACGGGGTCAAAGTATTACCTATGAATGAATGACAAAAGAATCTTCTGGCTAGGGTGTTAGATATATTTATGCATTTTTGGTTTTGTTTTTAAATCAAGCACATCAACCTCAAGCCCGTTTAGCAATGAGORF Start: ATG at 413ORF Stop: TGA at 1970SEQ ID NO:130519 aaMW at 57552.4 kDNOV41a,MTCPDKPGQLINWFICSLCVPRVRRLWSSRRPRTRRNLLLGTACAIYLGFLVSQVGRACG57814-01 Protein SequenceSLQHGQAAEKGPHRSRDTAEPSFPEIPLDGTLAPPESQGNGSTLQPNVVYITLRSERSKPANIRGTVKPKRRKKHAVASAAPGQEALVGPSLQPQEAAREADAVAPGYAQGANLVKIGERPWRLVRGPGVRAGGPDFLQPSSRESNIRIYSESAPSWLSKDDIRRMRLLADSAVAGLRPVSSRSGARLLVLEGGAPGAVLRCGPSPCGLLKQPLDMSEVFAFHLDRILGLNRTLPSVSRKAEFIQDGRPCPIILWDASLSSASNDTHSSVKLTWGTYQQLLKQKCWQNGRVPKPESGCTEIHHHEWSKMALFDFLLQIYNRLDTNCCGFRPRKEDACVQNGLRPKCDDQGSAALAHIIQRKHDPRHLVFTDNKGFFDRSEDNLNFKLLEGIKEFPASAVSVLKSQHLRQKLLQSLFLDKVYWESQGGRQGIEKLIDVIEHRAKILITYINAHGVKVLPMNESEQ ID NO:1311740 bpNOV41b,GGCAGCTGAAGTCAGGAAACCATGCATCACATTAGCAGGAGCCAACTGCAGACTTTAACG57814-02 DNA SequenceACTCCGTTCAACATGTGGATGCGGCAGAGAAATGACCTGTCCAGACAAGCCGGGGCAGCTCATAAACTGGTTCATCTGCTCCCTGTGCGTCCCGCGGGTGCGTAAGCTCTGGAGCAGCCGGCGTCCAAGGACCCGGAGAAACCTTCTGCTGGGCACTGCGTGTGCCATCTACTTGGGCTTCCTGGTGAGCCAGGTGGGGAGGGCCTCTCTCCAGCATGGACAGGCGGCTGAGAAGGGGCCACATCGCAGCCGCGACACCGCCGAGCCATCCTTCCCTGAGATACCCCTGGATGGTACCCTGGCCCCTCCAGAGTCCCAGGGCAATGGGTCCACTCTGCAGCCCAATGTGGTGTACATTACCCTACGCTCCAAGCGCAGCAAGCCGGCCAATATCCGTGGCACCGTGAAGCCCAAGCGCAGGAAAAAGCATGCAGTGGCATCGGCTGCCCAAGGGCAGGAGGCTTTGGTCGGACCATCCCTTCAGCCGCAAGAAGCGGCAAGGGAAGCTGATGCTGTAGCACTGGGTACGCTCAGGAGCAAACTGGTTAAGATGGAGAGCGACCCTGAAGGTGGTGCGGGGTCGGGAGTGCGAGCCGGGGGCCCAGACTTCCTGCAGCCCAGCTCCAGGGAGAGCAACATTAGGATCTACAGCGAGAGCGCCCCCTCCTGGCTGAGCAAAGATGACATCCGAAGAATGCGACTCTTGGCGGAGAGCGCAGTGGCAGGGCTCCGGCCTGTGTCCTCTAGGAGCGGAGCCCGTTTGCTGGTGCTGGAGGGGGGCGCACCTGGCGCTGTGCTCCGCTGTGGCCCTAGCCCCTGTGGGCTTCTCAAGCAGCCCTTGGACATGAGTGAGGTGTTTGCCTTCCACCTAGACAGGATCCTGGGGCTCAACAGGACCCTGCCGTCTGTGAGCAGGAAAGCAGAGTTCATCCAAGATGGCCGCCCATGCCCCATCATTCTTTGGCATGCATCTTTATCTTCAGCAAGTAATGACACCCATTCTTCTGTTAAGCTCACCTGGGGAACTTATCAGCAGTTGCTGAAACAGAAATGCTGGCAGAATGGCCGAGTACCCAAGCCTGAATCAGGTTGTACTGAAATACATCATCATGAGTGGTCCAAGATGGCACTCTTTGATTTTTTGTTACAGATTTATAATCGCTTAGATACAAATTGCTGTGGATTCAGACCTCGCAACGAAGATGCCTGTGTACAGAATGGATTGAGGCCAAAATGTGATGACCAAGGTTCTGCGGCTCTAGCACACATTATCCAGCGAAAGCATGACCCAAGGCATTTGGTTTTTATAGACAACAAGGGTTTCTTTGACAGGAGTGAAGATAACTTAAACTTCAAATTGTTAGAAGGCATCAAAGAGTTTCCAGCTTCTGCAGTTTCTGTTTTGAAGAGCCAGCACTTACGGCAGAAACTTCTTCAGTCTCTGTTTCTTGATAAAGTGTATTGGGAAAGTCAAGGAGGTAGACAAGGAATTGAAAAGCTTATCGATGTAATAGAACACAGAGCCAAAATTCTTATCACCTATATCAATGCACACGGGGTCAAAGTATTACCTATGAATGAATGACAAAAGAATCTTCTGGCTAGCGTGTTAGATATATTTATGCATTTTTGGTTTTGTTTTTAAATCAAGCACATCAACCTCAAGCCCGTTTAGCAATGAGORF Start: ATG at 90ORF Stop: TGA at 1641SEQ ID NO:132517 aaMW at 57179.9 kDNOV41b,MTCPDKPGQLINWFICSLCVPRVRKLWSSRRPRTRRNLLLGTACAIYLGFLVSQVGRACG57814-02 Protein SequenceSLQHGQAAEKGPHRSRDTAEPSFPEIPLDGTLAPPESQGNGSTLQPNVVYITLRSKRSKPANIRGTVKPKRRKKHAVASAAQGQEALVGPSLQPQEAAREADAVALGTLRSKLVKMESDPEGGAGSGVRAGGPDFLQPSSRESNIRIYSESAPSWLSKDDIRRMRLLADSAVAGLRPVSSRSGARLLVLEGGAPGAVLRCGPSPCGLLKQPLDMSEVFAFHLDRILGLNRTLPSVSRKAEFIQDGRPCPIILWDASLSSASNDTHSSVKLTWGTYQQLLKQKCWQNGRVPKPESGCTEIHHHEWSKMALFDFLLQIYNRLDTNCCGFRPRKEDACVQNGLRPKCDDQGSAALAHIIQRKHDPRHLVFIDNKGFFDRSEDNLNFKLLEGIKEFPASAVSVLKSQHLRQKLLQSLFLDKVYWESQGGRQGIEKLIDVIEHRAKILITYINAHGVKVLPMNE


[0540] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 41B.
216TABLE 41BComparison of NOV41a against NOV41b.Identities/NOV41a Residues/Similarities forProtein SequenceMatch Residuesthe Matched RegionNOV41b1 . . . 519493/519 (94%)1 . . . 517497/519 (94%)


[0541] Further analysis of the NOV41a protein yielded the following properties shown in Table 41C.
217TABLE 41CProtein Sequence Properties NOV41aPSort0.5500 probability located in endoplasmic reticulumanalysis:(membrane); 0.2404 probability located in lysosome(lumen); 0.1000 probability located in endoplasmicreticulum (lumen); 0.1000 probability located in outsideSignalPLikely cleavage site between residues 59 and 60analysis:


[0542] A search of the NOV41a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 41D.
218TABLE 41DGeneseq Results for NOV41aNOV41aIdentities/Residues/Similarities forGeneseqProtein/Organism/LengthMatchthe MatchedExpectIdentifier[Patent #, Data]ResiduesRegionValueAAU12276Human PRO6001 polypeptide1 . . . 519518/519 (99%)0.0sequence - Homo sapiens, 519 aa.1 . . . 519519/519 (99%)[WO200140466-A2, 7 JUN 2001]AAM39125Human polypeptide SEQ ID NO1 . . . 519518/519 (99%)0.02270 - Homo sapiens, 519 aa.1 . . . 519519/519 (99%)[WO200153312-A1, 26 JUL 2001]AAM40911Human polypeptide SEQ ID NO1 . . . 519491/527 (93%)0.05842 - Homo sapiens, 537 aa.19 . . . 537 495/527 (93%)[WO200153312-A1, 26 JUL 2001]AAM41373Human polypeptide SEQ ID NO212 . . . 512 130/316 (41%)1e−646304 - Homo sapiens, 479 aa.161 . . . 471 180/316 (56%)[WO200153312-A1, 26 JUL 2001]AAM39587Human polypeptide SEQ ID NO212 . . . 512 130/316 (41%)1e−642732 - Homo sapiens, 397 aa.79 . . . 389 180/316 (56%)[WO200153312-A1, 26 JUL 2001]


[0543] In a BLAST search of public sequence databases, the NOV41a protein was found to have homology to the proteins shown in the BLASTP data in Table 41E.
219TABLE 41EPublic BLASTP Results for NOV41aNOV41aIdentities/ProteinResidues/Similarities forAccessionMatchthe MatchedExpectNumberProtein/Organism/LengthResiduesPortionValueQ9ET25HYPOTHETICAL BASIC 1 . . . 519431/519(83%)0.0PROTEIN I-19 - Mus musculus 1 . . . 517462/519(88%)(Mouse), 517 aa.Q9NYZ0AD021 PROTEIN - Homo274 . . . 519246/246(100%) e−145sapiens (Human), 246 aa. 1 . . . 246246/246(100%)Q9UFP1HYPOTHETICAL 49.5 KDA212 . . . 512129/316(40%)2e−63PROTEIN - Homo sapiens130 . . . 440179/316(55%)(Human), 448 aa (fragment).


[0544] PFam analysis predicts that the NOV41a protein contains the domains shown in the Table 41F.
220TABLE 41FDomain Analysis of NOV41aIdentities/SimilaritiesNOV41afor theExpectPfam DomainMatch RegionMatched RegionValueSQS_PSY:109 . . . 1458/37(22%)9.9domain 1 of 129/37(78%)



Example 42

[0545] The NOV42 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 42A.
221TABLE 42ANOV42 Sequence AnalysisSEQ ID NO:1331294 bpNOV42a,GATGGCCACCTTGAACGTTGTACTGATGTTGATGCCCCTTGCCCAGTACATTTTCCATCG59327-01 DNA SequenceTGTTTTATAACTGTGCTACTGAAGTACTTGTGTGCAGAGTATGGCTGGAGGAATGCCATGTTGATCCAAGICCCCGTTTCCTTAAACCTGTTTGTTTTTGGGACCCTCATGAGGCCCCTCCCTCCTGGGAAAAACCCAAATGACCCAGAAGAGAAAGATCTGCGCGTCCTGCCCGCGCACTCCACAGAGTCTGTAATGTCAAATGGACAGCAGGGAAGAATAGAAGAGAAGGATGGCGGGTCTGGGAACGAGGAGACCCTCTGTGACCTGCAAGCCCAGGAGTGCAAGCCCAGGAGTGCCCCGATCAGGCCAGATCATGTGCGCTTTCCGGTTCTGAAGACGGTCAGCTGGCTCATTATGAGAGTCAAGAAGGGCTTCGAGGATTGGTACTCAGGCTATTTTGGGACAGCCAGCCTATTTACAAATCGAATGTTTGTAGCCTTTGTTTTCTGGGCTTCATTTGCATACAGCAGCTTTGTCATCTCCTTTATTCATCTCCCAGAAATCGTCAATTTGTATAACTTATTGGAGCAAACGAAGGTTTTCCCTCTGACTTCAATTATAGCAATAGTTCACATTGTTGGAAAAGTGATCCTGGGCGTCATAGCTGACTTACCTTGCATCAGTGTTTGGAATGTCTTCCTGTTGGCCAGCTTCGTTCTTGTCCTCAGTATTTTTGTTTTGCTGCCTTTGATGCATATGTACGCTGGCCTGGTGGTCATCTGCACACTGACAGGGTTTTCCAGCGGTTATTTCTCCCTAATGCCCATAGTGACTGAAGACTTGGTTGGCATTGAACATTTGGCCAATGCCTACGGCATCATCATCTGTGCTAATGGCATCTCTGCGTTGTTGGGACCACCTTTTGCAGGTAAACTGTCTGAGGTTTTAAGAGTTCATAGTGCATATAGATACGGTGTGTTAGCTCTGCGAGGAGACGGATGCAGAGCACTCACATCTTCTCTTATACATAGAAGTGAAATGGCTTTCTAAAGTTAGATCACTGGCCAGAGTTTTTGAGTCACAAGAGCTATTCCACAGATTTCCTTTAGAAAAACAATCACCACTGGCAGTCCACTTCAGTGACACAGAATGGGTTGCAGAACTTGCTTACTTATGTGACACATTCAACCTGCTCAATGAACTCAATCTGTCACTTCAGGGGAGAAGGACAACTGTGTTCAAGTCAGCAAATAAAGTGGCTACATTCAAAACCAAACTGGAATTACGGGGGTGORF Start: ATG at 2Stop: TAA at 1049SEQ ID NO:134349 aaMW at 38694.2 kDNOV42a,MATLNVVLMLNPLAQYIFHCFITVLLKYLCAEYGWRNAMLIQGAVSLNLFVFGTLMRPCG59327-01 Protein SequenceLPPGKNPNDPEEKDLRVLPAHSTESVNSNGQQGRIEEKDGGSGNEETLCDLQAQECKPRSAPIRPDHVRFPVLKTVSWLIMRVKKGFEDWYSGYFGTASLFTNRMFVAFVFWASFAYSSFVISFIHLPEIVNLYNLLEQTKVFFLTSIIAIVHIVGKVILGVIADLPCISVWNVFLLASFVLVLSIFVLLPLMHMYAGLVVICTLTGFSSGYFSLMPIVTEDLVGIEHLANAYGIIICANGISALLGPPFAGKLSEVLRVHSAYRYGVLALRGDGCRALTSSLIHRSEMAF


[0546] Further analysis of the NOV42a protein yielded the following properties shown in Table 42B.
222TABLE 42BProtein Sequence Properties NOV42aPSort0.6850 probability located in endoplasmic reticulumanalysis:(membrane); 0.6400 probability located in plasmamembrane; 0.4600 probability located in Golgibody; 0.1000 probability located in endoplasmicreticulum (lumen)SignalPLikely cleavage site between residues 32 and 33analysis:


[0547] A search of the NOV42a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 42C.
223TABLE 42CGeneseq Results for NOV42aNOV42aIdentities/Residues/SimilaritiesGeneseqProtein/Organism/LengthMatchfor theExpectIdentifier[Patent #, Data]ResiduesMatched RegionValueAAO07132Human polypeptide SEQ ID NO257 . . . 33149/77(63%)6e−2021024 - Homo sapiens, 107 aa. 5 . . . 8158/77(74%)[WO200164835-A2, 7 SEP 2001]AAY31642Human transport-associated protein-157 . . . 34254/197(27%)1e−074 (TRANP-4) - Homo sapiens, 465221 . . . 40186/197(43%)aa. [WO9941373-A2, 19 AUG 1999]AAY02737Human secreted protein encoded by198 . . . 34241/147(27%)9e−06gene 88 clone HKAFB88 - Homo 24 . . . 16465/147(43%)sapiens, 229 aa. [WO9902546-A1,21 JAN 1999]


[0548] In a BLAST search of public sequence databases, the NOV42a protein was found to have homology to the proteins shown in the BLASTP data in Table 42D.
224TABLE 42DPublic BLASTP Results for NOV42aIdentities/ProteinSimilaritiesAccessionNOV42a Residues/for the ExpectNumberProtein/Organism/LengthMatch ResiduesMatched PortionValueQ96NI7CDNA FLJ30794 FIS, CLONE 22 . . . 331250/312(80%) e−138FEBRA2001093, WEAKLY 1 . . . 310266/312(85%)SIMILAR TOMONOCARBOXYLATE(Human), 336 aa.Q9D1K01110004H10RIK PROTEIN - Mus 22 . . . 331220/312(70%) e−119musculus (Mouse), 336 aa. 1 . . . 310250/312(79%)AAL39716LD30953P - Drosophila142 . . . 31450/180(27%)2e−15melanogaster (Fruit fly), 894 aa.665 . . . 84389/180(48%)Q9V9B3CG3409 PROTEIN - Drosophila142 . . . 31450/180(27%)2e−15melanogaster (Fruit fly), 800 aa.571 . . . 74989/180(48%)Q9W0L6CG13907 PROTEIN - Drosophila157 . . . 33155/178(30%)1e−14melanogaster (Fruit fly), 816 aa.565 . . . 73891/178(50%)


[0549] PFam analysis predicts that the NOV42a protein contains the domains shown in the Table 42E.
225TABLE 42EDomain Analysis of NOV42aIdentities/SimilaritiesNOV42afor theExpectPfam DomainMatch RegionMatched RegionValueoxidored_q3:197 . . . 31425/177 (14%)9.1domain 1 of 173/177 (41%)



Example 43

[0550] The NOV43 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 43A.
226TABLE 43ANOV43 Sequence AnalysisSEQ ID NO:135455 bpNOV43a,TAGAACTGTGTTGAGCTCTCACCCATCACGATGAGCAACAAATTCTTGGGAACCTGGACG59494-01 DNA SequenceAGCTGGTCTCCAGTGAAAACTTTGAGGATTACATGAAAGAACTGGGAGTGAATTTCGCAGCCCGGAACATGGCAGGGTTAGTGAAACCGACAGTAACTATTAGTGTTGATGGGAAAATGATGACCATAAGAACAGAAAGTTCTTTCCAGGACACTAAGATCTCCTTCAAGCTGGGGGAAGAATTTGATGAAACTACAGCAGACAACCGGAAAGTAAAGAGCACCATAACATTAGAGAATGGCTCAATGATTCACGTCCAAAAATGGCTTGGCAAAGAGACAACAATCAAAAGAAAAATTGTGGATGAAAAAATGGTAGTGGAATGTAAAATGAATAATATTGTCAGCACCAGAATCTACGAAAAGGTCTGAAAAATCATTTCTTCATTGAAGTGGCTORF Start: ATG at 31ORF Stop: TGA at 427SEQ ID NO:136132 aaMW at 15096.4 kDNOV43a,MSNKFLGTWKLVSSENFEDYMKELGVNFAARNMAGLVKPTVTISVDGKMMTIRTESSFCG59494-01 Protein SequenceQDTKISFKLGEEPDETTADNRRVKSTITLENGSMIHVQKWLGKETTIKRKIVDEKMVVECKMNNIVSTRIYEKV


[0551] Further analysis of the NOV43a protein yielded the following properties shown in Table 43B.
227TABLE 43BProtein Sequence Properties NOV43aPSort0.6500 probability located in cytoplasm; 0.1000analysis:probability located in mitochondrial matrix space;0.1000 probability located in lysosome (lumen);0.0053 probability located in microbody (peroxisome)SignalPNo Known Signal Sequence Predictedanalysis:


[0552] A search of the NOV43a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 43C.
228TABLE 43CGeneseq Results for NOV43aNOV43aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAW40227Human myelin P2 protein-Homo1 . . . 130 89/130 (68%)2e−47sapiens, 136 aa. [WO9803647-A2,1 . . . 130107/130 (81%)29 JAN. 1998]AAW40228Bovine myelin P2 protein-Bos1 . . . 130 89/130 (68%)9e−47taurus, 136 aa. [WO9803647-A2,1 . . . 130106/130 (81%)29 JAN. 1998]AAY90320Human AFABP protein sequence-1 . . . 131 84/131 (64%)3e−46Homo sapiens, 132 aa.1 . . . 131110/131 (83%)[WO200047734-A1,17 AUG. 2000]AAY90319Mouse AFABP protein sequence-1 . . . 131 83/131 (63%)7e−45Mus sp, 132 aa. [WO200047734-1 . . . 131108/131 (82%)A1, 17 AUG. 2000]AAG66576Mouse MDGI polypeptide-Mus1 . . . 131 73/131 (55%)6e−40sp, 133 aa. [U.S. Pat.1 . . . 131103/131 (77%)No. 6232291-B1, 15 MAY 2001]


[0553] In a BLAST search of public sequence databases, the NOV43a protein was found to have homology to the proteins shown in the BLASTP data in Table 43D.
229TABLE 43DPublic BLASTP Results for NOV43aNOV43aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueMPRB2myelin P2 protein-rabbit, 132 aa.1 . . . 132 95/132 (71%)3e−491 . . . 132109/132 (81%)P02691Myelin P2 protein-Oryctolagus2 . . . 132 94/131 (71%)1e−48cuniculus (Rabbit), 131 aa.1 . . . 131108/131 (81%)MPHU2myelin P2 protein [validated]-1 . . . 132 92/132 (69%)3e−48human, 132 aa.1 . . . 132109/132 (81%)Q90X56ADIPOCYTE FATTY ACID1 . . . 131 86/131 (65%)1e−47BINDING PROTEIN-Gallus1 . . . 131113/131 (85%)gallus (Chicken), 132 aa.P02689Myelin P2 protein-Homo sapiens2 . . . 132 91/131 (69%)1e−47(Human), 131 aa.1 . . . 131108/131 (81%)


[0554] PFam analysis predicts that the NOV43a protein contains the domains shown in the Table 43E.
230TABLE 43EDomain Analysis of NOV43aIdentities/PfamNOV43aSimilarities forExpectDomainMatch Regionthe Matched RegionValuelipocalin: domain 1 of4 . . . 132 45/157 (29%)3.2e−361113/157 (72%)



Example 44

[0555] The NOV44 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 44A.
231TABLE 44ANOV44 Sequence AnalysisSEQ ID NO:1371561 bpNOV44a,AAGAATTGTAGCTCTCCACTGAATTGCAGGGGTTCTTGAATGTTGTCAACATTTGGAGCG59432-01 DNA SequenceGCAGTTGGAGGAGGGAGCTCTATTGATGAAAAATGGCTACATATTCAAAATTTCAGTGTATACCAGGAAGATAATTCAATTCAATCTCTGGCTTACCCAAAGAATCTTGGAGTTACTGCCAATGAGGAAATCCCCAGGGTCTAATAAAAATATCTTTAGGAGTGAAGGAGTTAACTGAGTGTGTAAGCTTTATCTTCTGTCCAATGGACTTGTGGTTTGCTTATAAAACTCTCCAGTAAATAATTGTTAGAGACCTGTCATTGATAGCAGTTGCTAGTTGCTGCCTTTTAAGAGCTCGTTGATTCCTCTGCAAGGTGGTGCAGCATCCTCTGTCCCTTCATTCATTTCAGATCTACTCAGGTCTCCCTGTAAACAGATCTCTCGGATCAATAAGCATGAATGACGAAGACTACACCACCATCTATGACACAATCCAAAATGAGAGGACGTATGAGGTTCCAGACCAGCCAGAAGAAAATGAAAGTCCCCATTATGATGATGTCCATGAGTACTTAAGGCCAGAAAATGATTTATATGCCACTCAGCTGAATACCCATGAGTATGATTTTGTGTCAGTCTATACCATTAAGGGTGAAGAGACCAGCTTGGCCTCTGTCCAGTCAGAAGACAGAGGCTACCTCCTGCCTGATGAGATATACTCTGAACTCCAGGAGGCTCATCCAGGTGAGCCCCAGGAGGACAGGGGCATCTCAATGGAAGGGTTATATTCATCAACCCAGGACCAGCAACTCTGCGCAGCAGAACTCCAGGAGAATGGGAGTGTGATGAAGGAAGATCTGCCTTCTCCTTCAAGCTTCACCATTCAGCACAGTAAGGCCTTCTCTACCACCAAGTATTCCTGCTATTCTGATGCTGAAGGTTTGGAAGAAAAGGAGGCAGCTCACATGAACCCTGAGATTTACCTCTTTGTGAAGGTAAGGTCTGCCTCTGACAGGCATACCCTGTTCATGCAGATATTATGGCTGGTGTTTTATTTTGCTCTGAATGACCAGGGAAAGATTCATAATGCCATGGTCCTTGGATCTCAATACATATTCAGGAGTCGGAGGGACTAAATCAGTCATTAGAGTGTACTCAGCTCTTCACAAAATTAGAGGAATTGGAAGGTGCATTTAAAGCACGTATTTAATCACTGACTTTTACATACCATGGGCAAAGTATTTTTCAAAACGGTTCACATAAGTGAGCCATAACTGCTGCCCAAATCCTTGCCATTGTGGCTGACATTAAGTACATTTTTCTGTCTGGTTAAATTTCCTTTGTCGACATGTTTAAAAGTGAAACCAAAGCTTGTGAAAGAAAGACCTTCTTGTGCTTCTAAGGTCACAGATTTGTCAGATAGGTGGTCAATAAAGGCTATCTCTGTCACTAGCTTGCCCCTTTGGCACCAATATAACTAAAAATTTGATGAAGTCAAATGATTTCAGTAGTAGTAAGACACTACCAGTGTTAATGTTTAATACTTACGATATCTAAACAGAAORF Start: ATG at 454ORF Stop: TAA at 1132SEQ ID NO:138226 aaMW at 26132.2 kDNOV44a,MNDEDYSTIYDTIQNERTYEVPDQPEENESPHYDDVHEYLRPENDLYATQLNTHEYDFCG59432-01 Protein SequenceVSVYTIKGEETSLASVQSEDRGYLLPDEIYSELQEAHPGEPQEDRGISMEGLYSSTQDQQLCAAELQENGSVMKEDLPSPSSFTIQHSKAFSTTKYSCYSDAEGLEEKEGAHMNPEIYLFVKVRSASDRHTLFMQILWLVFYFALNDQGKIHNAMVLGSQYIFRSRRDSEQ ID NO:139809 bpNOV44b,ATCCTCTGTCCCTTCATTCATTTCAGATCTACTCAGGTCTCCCTGTAAACAGATCTCTCG59432-02 DNA SequenceCGGATCAATAAGCATGAATGACGAAGACTACGGCACCATCTATGACACAATCCAAAATGAGAGGACGTATGAGGTTCCAGACCAGCCAGAAGAAAATGAAAGTCCCCATTATGATGATGTCCATGAGTACTTAAGGCCAGAAAATGATTTATATGCCACTCAGCTGAATACCCATGAGTATGATTTTGTGTCAGTCTATACCATTAAGGGTGAAGAGACCAGCTTGGCCTCTGTCCAGTCAGAAGACAGAGGCTACCTCCTGCCTGATGAGATATACTCTGAACTCCAGGAGGCTCATCCAGGTGAGCCCCAGGAGGACAGGGGCATCTCAATGGAAGGGTTATATTCATCAACCCAGGACCAGCAACTCTGCGCAGCAGAACTCCAGGAGAATGGGAGTGTGATGAAGGAAGATCTGCCTTCTCCTTCAAGCTTCACCATTCAGCACAGTAAGGCCTTCTCTACCACCAAGTATTCCTGCTATTCTGATGCTGAAGGTTTGGAAGAAAAGGAGGGAGCTCACATGAACCCTGAGATTTACCTCTTTGTGAAGGTAAGGTCTGCCTCTGACAGGCATACCCTGTTCATGCAGATATTATGGCTGCTGTTTTATTTTCCTCTGAATGACCAGGGAAAGATTCATAATGCCATGGTCCTTGGATCTCAATACATATTCAGGAGTCGGAGGGACTAAATCAGTCATTAGAGTGTACTCAGCTCTTCACAAAATTAGAGGAATTGGAAGGTGCATORF Start: ATG at 72ORF Stop: TAA at 750SEQ ID NO:140226 aaMW at 26102.2 kDNOV44b,MNDEDYGTIYDTIQNERTYEVPDQPEENESPHYDDVHEYLRPENDLYATQLNTHEYDFCG59432-02 Protein SequenceVSVYTIKGEETSLASVQSEDRGYLLPDEIYSELQEAHPGEPQEDRGISMEGLYSSTQDQQLCAAELQENGSVNKEDLPSPSSFTIQHSKAFSTTKYSCYSDAEGLEEKEGAHMNPEIYLFVKVRSASDRHTLFMQILWLVFYFALNDQGKIHNANVLGSQYIFRSRRD


[0556] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 44B.
232TABLE 44BComparison of NOV44a against NOV44b.Identities/ProteinNOV44a Residues/Similarities forSequenceMatch Residuesthe Matched RegionNOV44b1 . . . 226225/226 (99%)1 . . . 226225/226 (99%)


[0557] Further analysis of the NOV44a protein yielded the following properties shown in Table 44C.
233TABLE 44CProtein Sequence Properties NOV44aPSort0.6500 probability located in cytoplasm; 0.1000analysis:probability located in mitochondrial matrix space;0.1000 probability located in lysosome (lumen);0.0000 probability located in endoplasmic reticulum(membrane)SignalPNo Known Signal Sequence Predictedanalysis:


[0558] A search of the NOV44a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 44D.
234TABLE 44DGeneseq Results for NOV44aNOV44aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueNo Significant Matches Found


[0559] In a BLAST search of public sequence databases, the NOV44a protein was found to have homology to the proteins shown in the BLASTP data in Table 44E.
235TABLE 44EPublic BLASTP Results for NOV44aNOV44aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueQ96JT5CLIC5B-Homo sapiens (Human),1 . . . 200185/202 (91%) e−104410 aa.1 . . . 202191/202 (93%)Q9NPY9DJ447E21.4 (SIMILAR TO1 . . . 180180/180 (100%) e−103BOVINE CHLORIDE CHANNEL1 . . . 180180/180 (100%)PROTEIN (P64))-Homo sapiens(Human), 180 aa (fragment).A47104chloride channel 64K chain-1 . . . 197104/231 (45%)1e−39bovine, 437 aa.1 . . . 229133/231 (57%)P35526Chlorine channel protein p64-Bos1 . . . 197103/231 (44%)1e−38taurus (Bovine), 437 aa.1 . . . 229131/231 (56%)


[0560] PFam analysis predicts that the NOV44a protein contains the domains shown in the Table 44F.
236TABLE 44FDomain Analysis of NOV44aIdentities/PfamNOV44aSimilarities forExpectDomainMatch Regionthe Matched RegionValueNo Significant Matches Found



Example 45

[0561] The NOV45 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 45A.
237TABLE 45ANOV45 Sequence AnalysisSEQ ID NO:141877 bpNOV45a,ACTTTGTCCTCTTGGGCTTCACACAGAATCCAAAGGAGCAGAAAGTACTTTTTGTTATCS59394-01 DNA SequenceGTTCTTGCTCTTCTACATTTTGACCATGGTGGGCAACCTGCTCATTGTAGTGACCGTAACTGTCAGTGACACCCTGGGCTCACCAATGTACTTCTTTCTTGCTGGCTTATCATTTATAGATATCATTTATTCTTCATCCATTTCCCCCAGATTGATTTCAGGCTTGTTCTTTGGGAATAATTCCATATCCTTCCAATCTTGCATGGCCCAGCTCTTTATCGAGCACATTTTCGGTGGGTCAGAGGTCTTTCTCCTGTTGGTQATGGCCTATGACTGCTATGTGGCCATCTGTAAGCCCTTGCATTATTTGGTTATCATGAGACAATGGGTGTGTGTTCTGCTGCTGGTAGTGTCCTGGGTTGGAGGATTTCTGCACTCAGTATTTCAACTTAGCATTATTTATGGGCTCCCATTCTGTGGCCCCAATGTCATTGATCATTTTTTCTGTGACATGTATCCCTTATTGAAACTGGTCTGCACTGACACCCATGCTATTGGCCTCTTAGTGGTOGCCAATGGAGGACTGGCTTGCACTATTGTGTTTCTGCTCTTACTCATCTCTTATGGTGTCATCTTGCACTCTTTAAAGAACCTTAGTCAGAAAGGGAGGCAAAAAGCCCTCTCAACCTGCAGTTCCCACATGACTGTGGTTGTCTTCTTCTTTGTTCCTTGTATTTTTATGTATcCTAGACCTGCTAGGACCTTCCCCATTGACAAATCAGTGAGTGTGTTTTATACAGTCATAACCCCAATGCTGAACCCCTTAATCTACACTCTGAGAAATTCTGAGATGACAAGTGCTATGAAGAAGCTTTAGAGORF Start: TTT at 3ORF Stop: TAG at 873SEQ ID NO:142290 aaMW at 32485.7 kDNOV45a,FVLLGFTQNPKEQKVLFVMFLLFYILTMVGNLLIVVTVTVSETLGSPMYFFLAGLSFICG59394-01 Protein SequenceDIIYSSSISPRLISGLFFGNNSISFQSCMAQLFIEHIFGGSEVFLLLVMAYDCYVAICKPLHYLVIMRQWVCVVLLVVSWVGGFLHSVFQLSIIYGLPFCGPNVIDHFFCDMYPLLKLVCTDTHAIGLLVVANGGLACTIVFLLLLISYGVILHSLKNLSQKGRQKALSTCSSHMTVVVFFFVPCIFMYARPARTFPIDKSVSVFYTVITPMLNPLIYTLRNSEMTSAMKKL


[0562] Further analysis of the NOV45a protein yielded the following properties shown in Table 45B.
238TABLE 45BProtein Sequence Properties NOV45aPSort0.6400 probability located in plasma membrane; 0.4600analysis:probability located in Golgi body; 0.3700 probabilitylocated in endoplasmic reticulum (membrane);0.1000 probability located in endoplasmic reticulum (lumen)SignalPLikely cleavage site between residues 42 and 43analysis:


[0563] A search of the NOV45a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 45C.
239TABLE 45CGeneseq Results for NOV45aNOV45aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAU24536Human olfactory receptor 1 . . . 290273/290 (94%)e−155AOLFR21-Homo sapiens, 299 aa.10 . . . 299278/290 (95%)[WO200168805-A2,20 SEP. 2001]AAG71950Human olfactory receptor 1 . . . 290273/290 (94%)e−155polypeptide, SEQ ID NO: 1631-10 . . . 299278/290 (95%)Homo sapiens, 299 aa.[WO200127158-A2,19 APR. 2001]AAG72258Human olfactory receptor33 . . . 290234/258 (90%)e−131polypeptide, SEQ ID NO: 1939- 1 . . . 250240/258 (92%)Homo sapiens, 262 aa.[WO200127158-A2,19 APR. 2001]AAG72553Human OR-like polypeptide query 1 . . . 290198/290 (68%)e−121SEQ NO: 2234-10 . . . 299242/290 (83%)Homo sapiens, 327 aa.[WO200127158-A2,19 APR. 2001]AAG71909Human olfactory receptor 1 . . . 290198/290 (68%)e−121polypeptide, SEQ ID NO: 1590-10 . . . 299242/290 (83%)Homo sapiens, 327 aa.[WO200127158-A2,19 APR. 2001]


[0564] In a BLAST search of public sequence databases, the NOV45a protein was found to have homology to the proteins shown in the BLASTP data in Table 45D.
240TABLE 45DPublic BLASTP Results for NOV45aNOV45aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueQ9QW37OR18=ODORANT RECEPTOR- 1 . . . 290192/290 (66%) e−115Rattus sp, 307 aa.10 . . . 299237/290 (81%)Q96R66OLFACTORY RECEPTOR-57 . . . 269198/213 (92%) e−111Homo sapiens (Human), 213 aa 1 . . . 213202/213 (93%)(fragment).Q9R0K2ODORANT RECEPTOR 1 . . . 290177/290 (61%) e−105MOR18-Mus musculus10 . . . 299229/290 (78%)(Mouse), 308 aa.Q9R0K1ODORANT RECEPTOR A16- 1 . . . 290171/290 (58%) e−102Mus musculus (Mouse), 302 aa.10 . . . 299226/290 (76%)CAC88333SEQUENCE 34 FROM PATENT 1 . . . 290167/290 (57%)5e−99WO0164879-Homo sapiens10 . . . 299221/290 (75%)(Human), 309 aa.


[0565] PFam analysis predicts that the NOV45a protein contains the domains shown in the Table 45E.
241TABLE 45EDomain Analysis of NOV45aIdentities/PfamNOV45aSimilarities forExpectDomainMatch Regionthe Matched RegionValue7tm_1: domain 1 of 130 . . . 27650/268 (19%)4.4e−23174/268 (65%)



Example 46

[0566] The NOV46 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 46A.
242TABLE 46ANOV46 Sequence AnalysisSEQ ID NO:1431746 bpNOV46a,ATAATTCAGTTTGAAAACCAGTGGTTTCTCTTTCCTTCCCTATAGGTGTAAAGAATATCG59383-01 DNA SequenceCCAGCTGGTGGCTACAGTTCCCCCTCTGGTTTTGCTGCCATGCATCCTGGGCGAACTACTGGTAAAGGGCCCTCTACTCACACTCAGATTGACCAGCAACCTCCACGGCTTCTCATTGTGCACATTGCTCTACCGTCCTGGGCTGACATCTGCACCAACCTCTGTGAGGCTCTGCAGAACTTCTTCTCTCTAGCCTGCAGCTTGATGGGCCCCAGCCGCATGTCCCTGTTCAGTTTATACATGGTACAAGATCAGCATGAGTGCATCCTCCCTTTTGTGCAAGTGAAAGGGAACTTTGCTAGOTTGCAGACCTGCATCTCAGAACTCCGCATGTTACAGAGAGAAGGGTGTTTCAGATCACAAGGTGCTTCTCTGCGGCTGGCAGTAGAGGATGGGCTCCAGCAATTCAAACAATACAGCAGACATGTGACCACAAGGGCAGCTCTGACCTATACCTCCCTGGAGATTACTATTCTGACTTCTCAGCCTGGAAAAGAGGTGGTCAAACAGTTGGAGGAAGGGTTGAAAGATACAGACCTAGCCAGAGTCAGGAGGTTTCAGGTCGTTGAGGTCACAAAGGGAATCCTAGAGCACGTGGACTCAGCGTCTCCTGTTGAGGATACCAGCAATGATGAGAGTTCTATTCTGGGAACTGACATTGACCTTCAGACTATAGACAATGATATCGTCAGCATGGAGATTTTCTTCAAAGCCTGGCTACATAACAGTGGAACAGACCAAGAACAAATCCATCTTCTTCTTTCTTCACAGTGTTTCAGCAACATTTCCAGACCCAGAGATAATCCAATGTGTCTGAAATGTGATCTCCAAGAGCGACTGCTCTGCCCATCCCTACTCGCTGGCACAGCTGACGGCTCCTTGAGAATGGATGACCCTAAAGGAGACTTCATCACACTCTACCAGATGGCTTCCCAGTCATCGGCCTCTCATTACAAOCTCCAAGTGATCAAGGCTTTAAAATCTAGCGGGCTCTGCGAGTCATTGACATATGGACTCCCGTTCATCCTCAGACCTACAAGCTGTTGGCAGCTCGACTGGGATGAGCTGGAGACAAATCAGCAACATTTCCATGCTTTGTGTCACAGCCTGCTGAAAAGGGAATGGCTGCTGTTAGCCAAGGGGGAACCACCGGGCCCAGGACACAGCCAGAGAATTCCTGCCAGCACCTTCTATGTGATCATGCCGTCACACTCCCTCACACTGCTGGTAAAGGCGGTGGCCACGCGGGAACTGATGCTGCCCAGCACCTTCCCCCTGCTACCTGAGGACCCACATGATGATAGCCTTAAGAATAGCATGCTGGACAGCCTGGAGCTGGAGCCCACCTACAACCCCTTGCATGTTCAAAGCCACCTGTACTCACACCTGAGCAGCATCTATGCCAAGCCTCAGGGGCGGCTCCACCCACACTGGGAGAGCCGAGCTCCGAGAAAGACTGGGCAGTTGCAGACCAACCGAGCTCGAGCTACTGTGGCCCCCCTGCCTATGACTCCTGTCCCAGGCAGAGCCTCCAAGATGCCAGCAGCCAGCAAATCTTCCTCAGATGCCTTCTTCCTGCCTTCAGAGTGGGAGAAGGATCCCTCAAGGCCCTAAGTCACCAGCACCAGAGCCCAGCTGCCCAGCTTAACCATATCCATGCTCAGGTTCACATAATGGCTATCTGTGGTORF Start: ATG at 98ORF Stop: TAA at 1670SEQ ID NO:144524 aaMW AT 58691.3 kDNOV46a,MHPGRTTGKGPSTHTQIDQQPPRLLIVHIALPSWADICTNLCEALQNFFSLACSLMGPCG59383-01 Protein SequenceSRMSLFSLYMVQDQHECILPFVQVKGNFARLQTCISELRMLQREGCFRSQGASLRLAVEDGLQQEKQYSRHVTTRAALTYTSLEITILTSQPGKEVVKQLEEGLKDTDLARVRRFQVVEVTKGILEHVDSASPVEDTSNDESSILGTDIDLQTIDNDTVSMEIFFKAWLHNSGTDQEQIHLLLSSQCFSNISRPRDNPMCLKCDLQERLLCPSLLAGTADGSLRNDDPKGDFITLYQMASQSSASHYKLQVIKALKSSGLCESLTYGLPFILRPTSCWQLDWDELETNQQHFHALCHSLLKREWLLLAKGEPPGPGHSQRIPASTFYVIMPSHSLTLLVKAVATRELMLPSTFPLLPEDPHDDSLKNSMLDSLELEPTYNPLHVQSHLYSHLSSIYAKPQGRLHPHWESRAPRKTGQLQTNRARATVAPLPMTPVPGRASKNPAASKSSSDAFFLPSEWEKDPSRPSEQ ID NO:1451647 bpNOV46b,AAAGAATATCCAGCTGGTGGCTACAGTTCCCCCTCTGGTTTTGCTGCCATGCATCCTGCG59383-02 DNA SequenceGGCGAACTACTGGTAAAGGGCCCTCTACTCACACTCAGATTGACCAGCAACCTCCACGGCTTCTCATTGTGCACATTGCTCTACCGTCCTGGGCTGACATCTGCACCAACCTCTGTGAGGCTCTGCAGAACTTCTTCTCTCTAGCCTGCAGCTTGATGGGCCCCAGCCGCATGTCCCTGTTCAGTTTATACATGGTACAAGATCAGCATGAGTGCATCCTCCCTTTTGTGCAAGTGAAAOGGAACTTTGCTAGGTTGCAGACCTGCATCTCAGAACTCCGCATGTTACAGAGAGAAGGGTGTTTCAGATCACAAGGTGCTTCTCTGCGGCTGGCAGTAGAGGATGGGCTCCAGCAATTCAAACAATACAGCAGACATGTGACCACAAGGGCAGCTCTGACCTATACCTCCCTGGAGATTACTATTCTGACTTCTCAGCCTGGAAAAGAGGTGGTCAAACAGTTGGAGGAAGGGTTGAAAGATACAGACCTAGCCAGAGTCAGGAGGTTTCAGGTCGTTGAGGTCACAAAGGGAATCCTAGAGCACGTGGACTCAGCGTCTCCTGTTGAGGATACCAGCAATGATGAGAGTTCTATTCTGGGAACTGACATTGACCTTCAGACTATAGACAATGATATCGTCAGCATGGAGATTTTCTTCAAAGCCTGGCTACATAACAGTGGAACAGACCAGGAACAAATCCATCTTCTTCTTTCTTCACAGTGTTTCAGCAACATTTCCAGACCCAGAGATAATCCAATGTGTCTGAAATGTGATCTCCAAGAGCGACTGCTCTGCCCATCCCTACTCGCTGGCACAGCTGACGGCTCCTTGAGAATGGATGACCCTAAAGGAGACTTCATCACACTCCACCAGATGGCTTCCCAGTCATCGGCCTCTCATTACAAGCTCCAAGTGATCAAGGCTTTAAAATCTAGCGGGCTCTGCGAGTCATTGACATATGGACTCCCGTTCATCCTCAGACCTACAACCTGTTGGCAGCTGGACTGGGATGAGCTGGAGACAAATCAGCAACATTTCCATGCTTTGTGTCACAGCCTGCTGAAAAGGGAATGGCTGCTGTTAGCCAAGGGGGAACCACCGGGCCCAGGACACAGCCAGAGAATTCCTGCCAGCACCTTCTATGTGATCATGCCGTCACACTCCCTCACACTGCTGGTAAAGGCGGTGGCCACGCGGCAACTGATGCTGCCCAGCACCTTCCCCCTGCTGCCTGAGGACCCACATGATGATAGCCTTAAGAATGTGGAGAGCATGCTGGACAGCCTGGAGCTGOAGCCCACCTACAACCCCTTGCATGTTCAAAGCCACCTGTACTCACACCTGAGCAGCATCTATGCCAAGCCTCAGGGGCGGCTCCACCCACACTGGGAGAGCCGAGCTCCGAGAAAGCATCCCTGCAAGACTGGGCAGTTGCAGACCAACCGAGCTCGAGCTACTGTGGCCCCCCTGCCTATGACTCCTGTCCCAGGCAGAGCCTCCAAGATGCCAGCAGCCAGCAAATCTTCCTCAGATGCCTTCTTCCTGCCTTCAGAGTGGGAGAAGGATCCCTCAAGGCCCTAAGTCACCORF Start: ATG at 49ORF Stop: TAA at 1639SEQ ID NO:146530 aaMW at 59359.1 kDNOV46b,MHPGRTTGKGPSTHTQIDQQPPRLLIVHIALPSWADICTNLCEALQNFFSLACSLMGPCG59383-02 Protein SequenceSRMSLFSLYMVQDQHECILPFVQVKGNFARLQTCISELRMLQREGCFRSQGASLRLAVEDGLQQFKQYSRHVTTRAALTYTSLEITILTSQPGKEVVKQLEEGLKDTDLARVRRFQVVEVTKGTLEHVDSASPVEDTSNDESSILGTDIDLQTIDNDIVSMEIFFKAWLHNSGTDQEQIELLLSSQCFSNISRPRDNPMCLKCDLQERLLCPSLLAGTADGSLRMDDPKGDFITLHQMASQSSASUYKLQVIKALKSSGLCESLTYGLPFILRPTSCWQLDWDELETNQQHFHALCHSLLKREWLLLAKGEPPGPGHSQRIPASTFYVIMPSHSLTLLVKAVATRELMLPSTFPLLPEDPHDDSLKNVESMLDSLELEPTYNPLHVQSHLYSHLSSIYAKPQGRLHPHWESRAPRKHPCKTGQLQTNRARATVAPLPMTPVPGRASKMPAASKSSSDAPFLPSEWEKDPSRP


[0567] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 46B.
243TABLE 46BComparison of NOV46a against NOV46b.Identities/ProteinNOV44a Residues/Similarities forSequenceMatch Residuesthe Matched RegionNOV46b1 . . . 524509/530 (96%)1 . . . 530510/530 (96%)


[0568] Further analysis of the NOV46a protein yielded the following properties shown in Table 46C.
244TABLE 46CProtein Sequence Properties NOV46aPSort0.4500 probability located in cytoplasm; 0.3000analysis:probability located in microbody (peroxisome);0.1000 probability located in mitochondrial matrixspace; 0.1000 probability located in lysosome (lumen)SignalPNo Known Signal Sequence Predictedanalysis:


[0569] A search of the NOV46a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 46D.
245TABLE 46DGeneseq Results for NOV46aNOV46aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAM34317Peptide #8354 encoded by probe for259 . . . 31052/52 (100%)7e−23measuring placental gene expression- 1 . . . 5252/52 (100%)Homo sapiens, 52 aa.[WO200157272-A2, 9 AUG. 2001]ABB18624Protein #623 encoded by probe for101 . . . 14242/42 (100%)2e−16measuring heart cell gene expression- 1 . . . 4242/42 (100%)Homo sapiens, 42 aa.[WO200157274-A2, 9 AUG. 2001]AAM66343Human bone marrow expressed101 . . . 14242/42 (100%)2e−16probe encoded protein SEQ ID NO: 1 . . . 4242/42 (100%)26649-Homo sapiens, 42 aa.[WO200157276-A2, 9 AUG. 2001]AAM53955Human brain expressed single exon101 . . . 14242/42 (100%)2e−16probe encoded protein SEQ ID NO: 1 . . . 4242/42 (100%)26060-Homo sapiens, 42 aa.[WO200157275-A2, 9 AUG. 2001]AAM26622Peptide #659 encoded by probe for101 . . . 14242/42 (100%)2e−16measuring placental gene expression- 1 . . . 4242/42 (100%)Homo sapiens, 42 aa.[WO200157272-A2, 9 AUG. 2001]


[0570] In a BLAST search of public sequence databases, the NOV46a protein was found to have homology to the proteins shown in the BLASTP data in Table 46E.
246TABLE 46EPublic BLASTP Results for NOV46aNOV46aIdentities/ProteinResidues/SimilaritiesAccessionMatchfor theExpectNumberProtein/Organism/LengthResiduesMatched PortionValueQ9Z0E1D6MM5E PROTEIN - Mus1 . . . 524380/526(72%)0.0musculus (Mouse), 529 aa.1 . . . 526423/526(80%)Q96L07SIMILAR TO DNA SEGMENT,1 . . . 358358/358(100%)0.0CHR 6, MIRIAM MEISLER 5,1 . . . 358358/358(100%)EXPRESSED - Homo sapiens(Human), 365 aa.


[0571] PFam analysis predicts that the NOV46a protein contains the domains shown in the Table 46F.
247TABLE 46FDomain Analysis of NOV46aIdentities/SimilaritiesNOV46afor thePfam DomainMatch RegionMatched RegionExpect ValueRA: domain 1 of 1124 . . . 21418/115 (16%)8.465/115 (57%)



Example 47

[0572] The NOV47 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 47A.
248TABLE 47ANOV47 Sequence AnalysisSEQ ID NO:147960 bpNOV47a,AGGACTAAATAAAATGGCCTAAATTTAAATATGGATTGGGATTTCCATTCTCTTGCAGCG58526-01 DNA SequenceATGCCCAGAACCAAAGAAGAGGTCTGCCTGGTTTTCTTCCTGGAGCTCCAGACCCAGACCAAAGCCTTCCTGCCTCTTCCAATCCAGGGAACCAAGCATGGCAGCTGAGTCTCCCTCTGCCAAGCAGTTTCCTGCCAACAGTCAGTCTCCCTCCTGGTCTAGAATATTTAAGCCAGTTAGACCTGATAATTATACACCAGCAGGTGGAGCTGCTTGTGATACTTGGTACTGAGACCTCCAACAAATATGAGATTAAAAACAGCTTGGGACAAAGAATTTACTTTGCAGTGGAGGAAAGCATCTGCTTCAATCGTACTTTCTGTTCCACTCTGCGATCTTGCACCCTGAGGATCACAGATAACTCAGGTCGAGAGGTCATTACAGTGAACAGGCCCTTGAGATGTAACAGCTGCTGGTGCCCTTGCTACCTACAAGAGTTAGAAATCCAAGCCCCTCCTGGTACTATAGTTGGTTACGTTACGCAGAAGTGGGACCCCTTTCTGCCTAAATTCACAATCCAAAATGCAAACAAAGAAGATATTTTGAAAATTGTTGGTCCTTGTGTGACATGTGGCTGTTTTGGCGATGTGGATTTTGAGAAGGTGAAAACCATTAATGAAAAGCTTACAATTGGGAAGATTTCAAAGTACTGGTCAGGATTTGTAAATGATGTCTTCACAAATGCTGACAATTTCGGAATTCATGTTCCTGCAGATCTAGATGTAACAGTCAAAGCAGCAATGATCGGTGCCTGTTTTCTCTTTGTAAGTATGGGCTTTGAGAGCCCAGCCCTCCAAGATGAGAAAGAGTCAGTGTGGCAATTCAAAAAATCAGAGTGCCCTCTCACCTCCAAACAAGCCCACTTGTTCCCCAGCGATGGTTCTTAGCCAGACTGAAATGACORF Start: ATG at 31ORF Stop: TAG at 943SEQ ID NO:148304 aaMW at 33794.2 kDNOV47a,MDWDFHSLADAQNQRRGLPGFLPGAPDPDQSLPASSNPGNQAWQLSLPLPSSFLPTVSCG58526-01 Protein SequenceLPPGLEYLSQLDLIIIHQQVELLVILGTETSNKYEIKNSLGQRIYFAVEESICFNRTFCSTLRSCTLRITDNSGREVITVNRPLRCNSCWCPCYLQELEIQAPPGTIVGYVTQKWDPFLPKFTIQNANKEDILRIVGPCVTCGCFGDVDFEKVKTINEKLTIGKISKYWSGFVNDVFTNADNFGIRVPADLDVTVKAAMIGACFLFVSMGFESPALQDEKESVWQFKKSECPLTSKQAHLFPSDGS


[0573] Further analysis of the NOV47a protein yielded the following properties shown in Table 47B.
249TABLE 47BProtein Sequence Properties NOV47aPSort0.8500 probability located in endoplasmic reticulumanalysis:(membrane); 0.4400 probability located in plasmamembrane; 0.4244 probability located in microbody(peroxisome); 0.1000 probability located inmitochondrial inner membraneSignalPNo Known Signal Sequence Predictedanalysis:


[0574] A search of the NOV47a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 47C.
250TABLE 47CGeneseq Results for NOV47aNOV47aIdentities/Protein/Residues/Similarities forGeneseqOrganism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAG78341Human Mm-1 cell line derived24 . . . 282152/263 (57%)5e−84transplantability-associated gene 1b -60 . . . 318187/263 (70%)Homo sapiens , 318 aa.[WO200164894-A2, 7 SEP 2001]AAB24113Human phospholipid scramblase24 . . . 282152/263 (57%)5e−84HPLS protein sequence - Homo60 . . . 318187/263 (70%)sapiens , 318 aa. [CN1259574-A,12 JUL 2000]AAB24112Mouse phospholipid scramblase24 . . . 282152/263 (57%)5e−84MPLS protein sequence - Mus sp,60 . . . 318187/263 (70%)318 aa. [CN1259574-A, 12 JUL2000]AAY09309Human phospholipid scramblase -24 . . . 282152/263 (57%)5e−84Homo sapiens , 318 aa.60 . . . 318187/263 (70%)[WO9919352-A2, 22 APR 1999]AAY29323Human PL scramblase - Homo24 . . . 282152/263 (57%)5e−84sapiens , 318 aa. [WO9936536-A2,60 . . . 318187/263 (70%)22 JUL 1999]


[0575] In a BLAST search of public sequence databases, the NOV47a protein was found to have homology to the proteins shown in the BLASTP data in Table 47D.
251TABLE 47DPublic BLASTP Results for NOV47aNOV47aIdentities/ProteinResidues/Similarities forAccessionMatchthe MatchedExpectNumberProtein/Organism/LengthResiduesPortionValueQ9JJ00Phospholipid scramblase 1 (PL20 . . . 283150/267 (56%)4e−84scramblase 1) (Transplantability66 . . . 328191/267 (71%)associated protein 1) (TRA1) (NOR1) -Mus musculus (Mouse), 328 aa.Q99M50PHOSPHOLIPID SCRAMBLASE 1 -20 . . . 282150/266 (56%)6e−84Mus musculus (Mouse), 327 aa.66 . . . 327191/266 (71%)O15162Phospholipid scramblase 1 (PL24 . . . 282152/263 (57%)2e−83scramblase 1) (Erythrocyte60 . . . 318187/263 (70%)phospholipid scramblase) (Ca2 +dependent phospholipid scramblase 1)(MmTRA1b) - Homo sapiens(Human), 318 aa.P58195Phospholipid scramblase 1 (PL28 . . . 282145/256 (56%)3e−81scramblase 1) (Ca2 + dependent84 . . . 335183/256 (70%)phospholipid scramblase 1) - Rattusnorvegicus (Rat), 335 aa.Q9NRY7Phospholipid scramblase 2 (PL55 . . . 270135/217 (62%)le−75scramblase 2) (Ca2 + dependent 6 . . . 221164/217 (75%)phospholipid scramblase 2) - Homosapiens (Human), 224 aa.


[0576] PFam analysis predicts that the NOV47a protein contains the domains shown in the Table 47E.
252TABLE 47EDomain Analysis of NOV47aIdentities/PfamNOV47aSimilaritiesExpectDomainMatch Regionfor the Matched RegionValueNo Significant Matches Found



Example 48

[0577] The NOV48 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 48A.
253TABLE 48ANOV48 Sequence AnalysisSEQ ID NO:149957 bpNOV48a,CCCCTGCTGGTGCCCAAGACCACCGTGGAAGGAATGGCTAAAGAGGAGACAAGTGAGTCG57851-01 DNA SequenceTAGAATGGGGCTTGTTACCCCCAGAAGAATTTTCCCAAGTGAATGGAATCATTCTTCAAAAGAAAATGTGCGATTTCTGGGATAAGATCTGGAACTTCCAAGCCAAGCCTGATGACCTGCTCATTGCTTCTTACCCCAAAGCAGGTACCACTTGGACACAGGAAATTGTAGATCTGATACAAAATGATGGCGATATTGAGAAAAGCAGGCGCGCTTCCATTCAACTTCAACACCCTTTCCTGGAGTGGATAAGAATGACACACGCCAGGAAAATTTTTGCAGGGATTGACCAGGCTAACACAATGCCTTCCCCAAGGACCCTGAAAACTCATCTTCCTGTACAACTACTGCCTCCATCCTTCTGGGAGGAAAACTGTAAGATAATCTATGTGGCAAGAAATGCCAAGGATAACCTGGTGTCCTACTACCATTTTCAAAGGATGAGCAAAGCACTCCCTGACGTTTTGACAGTGGGAGAATACATTATGTGTGGGGAAGTGTTGTGGGGAATATGGGAAGAGATTCGGACTTGGCAACTGCATAGGTTGTTCTGCTGGTTCTTTGATCATGCTTCTGAGAATCCTAGAAAGTTCAAAAGGATAATGGAATTTATGGGGAATAAACTAGATGAAGATCCTGTCAAAAGAATTGTTCAGCACACATCTTTTGAAAGTAAGAAGAAAAACCAGATGACCAACTATGTAATGATAACCTGTGACATCATGGACCACTCCATCTCCCCATTTATGAGGAAAGGGACCGTTGGAGAGTGGAAGGATTACTTCTCAGCAGCACACAATAAGAGATTTGATGAAGACAGGAAAATGGCTGACTCTTCTCTGACCTTCCACACGGAGCTCTAAAGAGAGAGAGACAAAGTCTATACTACACAGGGGCACORF Start: ATG at 34ORF Stop: TAA at 919SEQ ID NO:150295 aaMW at 34853.7 kDNOV48a,MAKEETSELEWGLLPPEEFSQVNGIILQKKMCDFWDKIWNFQAKPDDLLIASYPKAGTCG57851-01 Protein SequenceTWTQEIVDLIQNDGDIEKSRRASIQLQHPFLEWIRMTHARKIFAGIDQANTMPSPRTLKTHLPVQLLPPSFWEENCKIIYVARNAKDNLVSYYHFQRMSKALPDVLTVGEYIMCGEVLWGIWEEIRTWQLHRLFCWFFDHASENPRKFKRIMEFMGNKLDEDPVKRIVQHTSFESKKKNQMTNYVNITCDIMDESISPFMRKGTVGEWKDYFSAAQNKRFDEDRKMADSSLTFHTEL


[0578] Further analysis of the NOV48a protein yielded the following properties shown in Table 48B.
254TABLE 48BProtein Sequence Properties NOV48aPSort0.6400 probability located in microbody (peroxisome);analysis:0.4500 probability located in cytoplasm; 0.1000 probabilitylocated in mitochondrial matrix space; 0.1000 probabilitylocated in lysosome (lumen)SignalPNo Known Signal Sequence Predictedanalysis:


[0579] A search of the NOV48a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 48C.
255TABLE 48CGeneseq Results for NOV48aNOV48aIdentities/Protein/Residues/Similarities forGeneseqOrganism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAE12209Human ST drug-metabolising16 . . . 295137/293 (46%)9e−74protein 2 encoded by DNA15 . . . 304200/293 (67%)transcript 2 - Homo sapiens, 304 aa.[WO200172977-A2, 4 OCT 2001]AAE12210Human ST drug-metabolising16 . . . 295129/293 (44%)1e−67protein 3 encoded by cDNA - Homo15 . . . 304190/293 (64%)sapiens, 304 aa. [WO200172977-A2, 4 OCT 2001]AAE12208Human ST drug-metabolising16 . . . 295128/293 (43%)6e−67protein 1 encoded by DNA15 . . . 304190/293 (64%)transcript 1 - Homo sapiens, 304 aa.[WO200172977-A2, 4 OCT 2001]AAE05178Human drug metabolising enzyme16 . . . 295128/293 (43%)1e−66(DME-9) protein - Homo sapiens,15 . . . 304189/293 (63%)304 aa. [WO200151638-A2,19 JUL 2001]AAY67294Human STP2 (phenol15 . . . 295133/292 (45%)5e−66sulphotransferase 2) amino acid10 . . . 295186/292 (63%)sequence - Homo sapiens, 295 aa.[WO9964630-A1, 16 DEC 1999]


[0580] In a BLAST search of public sequence databases, the NOV48a protein was found to have homology to the proteins shown in the BLASTP data in Table 48D.
256TABLE 48DPublic BLASTP Results for NOV48aNOV48aIdentities/ProteinResidues/Similarities forAccessionMatchthe MatchedExpectNumberProtein/Organism/LengthResiduesPortionValueQ90WR6SULFOTRANSFERASE 1C - 3 . . . 295170/304 (55%)3e−94Gallus gallus (Chicken), 307 aa. 5 . . . 307218/304 (70%)P50237N-hydroxyarylamine 1 . . . 295172/308 (55%)3e−92sulfotransferase (EC 2.8.2.-) 1 . . . 304222/308 (71%)(HAST-I) - Rattus norvegicus(Rat), 304 aa.O70262PHENOL SULFOTRANSFERASE - 18 . . . 295164/289 (56%)1e−91Mus musculus (Mouse), 304 aa.19 . . . 304215/289 (73%)O75897Sulfotransferase 1C2 (EC 2.8.2.-)22 . . . 292160/282 (56%)1e−87(SULT1C) (SULT1C#2) - Homo22 . . . 299203/282 (71%)sapiens (Human), 302 aa.O00338Sulfotransferase 1C1 (EC 2.8.2.-)18 . . . 295149/289 (51%)1e−80(SULT1C#1) (ST1C2)12 . . . 296201/289 (68%)(humSULTC2) - Homo sapiens(Human), 296 aa.


[0581] PFam analysis predicts that the NOV48a protein contains the domains shown in the Table 48E.
257TABLE 48EDomain Analysis of NOV48aIdentities/PfamNOV48aSimilaritiesExpectDomainMatch Regionfor the Matched RegionValueSulfotransfer:23 . . . 285116/298 (39%)6.2e−82domain 1 of 1207/298 (69%)



Example 49

[0582] The NOV49 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 49A.
258TABLE 49ANOV49 Sequence AnalysisSEQ ID NO:1511934 bpNOV49a,CTTGATTACGGAGACTGAACCTTCATAGGGTGCGCACTTACCAAGGACAGGAAGGTTTCG59377-01 DNA SequenceCTCTGTTTGAAGGGCTTTAAACTTATAACAAAGAAAATAAAAATGACGACTTCGTCTATCAGACGGCAGATGAAAAACATCGTGAACAATTACTCAGAGGCAGAAATCAAAGTCCGGGAAGCCACCTCCAATGACCCGTGGGGCCCGTCCAGTTCTCTGATGACCGAGATTGCCGACCTGACCTACAACGTGGTGGCCTTCTCGGAGATCATGAGCATGGTGTGGAAGCGGCTGAATGACCATGGCAAGAACTGGCGGCATGTGTACAAGGCGCTGACCCTGCTGGACTACCTCATCAAGACAGGCTCCGAACGTGTGGCCCAGCAGTGCCGGGAGAACATCTTCGCCATCCAGACCCTGAAGGACTTCCAGTACATTGACCOAGATGGCAAGGACCAGGGCATCAATGTGCGTGAGAAGTCAAAGCAACTGGTGGCTCTCCTCAAGGACGAGGAACGGTTGAAGGCTGAGAGGGCCCAGGCTCTCAAAACCAAAGAGCGCATGGCCCAGGTTGCCACTGGCATGGGCAGCAACCAGATCACCTTTGGGCGAGGCTCCAGCCAGCCCAACCTCtCCACCAGCCACTCGGAGCAGGAGTATGGCAAGGCCGGGGGCTCCCCGGCCTCCTACCATGGCTCCACCTCCCCGCGAGTGTCCTCCGAGCTGGAGCAAGCCCGGCCCCAGACTAGTGGAGAAGAGGAGCTTCAGCTGCAGCTGGCACTTGCCATGAGCAGAGAAGTGGCTGAGCAGGAAGAACGCCTCAGGCGGGGTGATGACCTCAGATTACAGATGGCCCTGGAAGAAAGCCGAAGGGACACAGTTAAAATTCCAAAAAAGAAAGAGCAGACTACGCTGTTGGATTTAATGGATGCTCTCCCCAGCTCGGGCCCCGCGGCCCACAAAGCAGAGCCCTGGGGCCCGTCAGCCTCCACTAACCAGACCAACCCCTGGGGCGGGCCAGCGGCTCCTGCGAGTACTTCAGACCCCTGGCCATCGTTTGGTACCAAGCCAGCTGCCTCCATTGACCCATGGGGGGTGCCCACTGGAGCCACCGCACAATCTGTCCCCAAGAACTCGGACCCCTGGGCAGCTTCACAGCAGCCTGCCTCCAGTGCTGGGAAAAGAGCTTCTGACGCGTGGGGCGCAGTCTCCACCACCAAGCCCGTGTCTGTCTCTGGGTCCTTTGAGCTCTTCAGTAATCTGAATGGTACAATTAAAGATGACTTTTCTGAATTTGACAACCTTCGGACTTCAAAAAAAACAGCCGAATCTGTGACCTCTCTGCCATCCCAAAACAATGGAACTACCAGCCCTGACCCCTTTGAGTCTCAACCCCTGACTGTCGCCTCAAGCAAGCCCAGCAGTGCCCGGAAAACACCTGAGTCCTTCCTGGGCCCCAACGCGGCCCTGGTGAACCTGGACTCACCGGTGACCAGGCCTGCCCCACCAGCCCAGTCCCTCAACCCTTTCCTGGCACCAGGTGCTCCCGCCACCTCGGCCCCTGTTAACCCTTTCCAGGTGAACCAGCCCCAGCCGCTGACACTGAACCAGCTTCGGGGGAGCCCAGTCCTGGGGACCAGCACATCCTTTGGGCCTGGCCCAGGAGTGGAGTCCATGGCTGTGGCCTCGATGACCTCCGCGGCCCCACAGCCAGCTCTGGGGGCCACTGGTTCCTCTCTGACACCACTGGGCCCTGCAATGATGAACATGGTGGGCAGTGTCGGTATACCCCCATCAGCAGCCCAGGCCACTGGCACAACCAACCCTTTCCTTCTCTAGTGCCTGGGCCTGGGACCCACCCAGAGCACCTGTGCTGGAGGATGCCGAGCAGGCACTCTCGTCTGTGGCACGGGATCCAAGAGTTTGGQGATTAGGGORF Start: ATG at 101ORF Stop: TAG at 1835SEQ ID NO:152578 aaMW at 61651.2 kDNOV49a,MTTSSIRRQNKNIVNNYSEAEIKVREATSNDPWGPSSSLMTEIADLTYNVVAFSEIMSCG59377-01 Protein SequenceMVWKRLNDHGKNWRHVYKALTLLDYLIKTGSERVAQQCRENIFAIQTLKDFQYIDRDGKDQGINVREKSKQLVALLKDEERLKAERAQALKTKERMAQVATGMGSNQITFGRGSSQPNLSTSESEQEYGKAGGSPASYHGSTSPRVSSELEQARPQTSGEEELQLQLALAISREVAEQEERLRRGDDLRLQMALEESRRDTVKIPKKKEQTTLLDLMDALPSSGPAAQKAEPWGPSASTNQTNPWGGPAAPASTSDPWPSFGTKPAASIDPWGVPTGATAQSVPKNSDPWAASQQPASSAGKRASDAWGAVSTTKPVSVSGSFELFSNLNGTIKDDFSEFDNLRTSKKTAESVTSLPSQNNGTTSPDPFESQPLTVASSKPSSARKTPESFLGPNAALVNLDSLVTRPAPPAQSLNPFLAPGAFATSAPVNPFQVNQPQPLTLNQLRGSPVLGTSTSFGPGPGVESMAVASMTSAAPQPATGATGSSLTPLGPAMMNMVGSVGIPPSAAQATGTTNPFLL


[0583] Further analysis of the NOV49a protein yielded the following properties shown in Table 49B.
259TABLE 49BProtein Sequence Properties NOV49aPSort0.4936 probability located in mitochondrial matrix space;analysis:0.3000 probability located in nucleus; 0.2087 probabilitylocated in mitochondrial inner membrane; 0.2087 probabilitylocated in mitochondrial intermembrane spaceSignalPNo Known Signal Sequence Predictedanalysis:


[0584] A search of the NOV49a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologousproteins shown in Table 49C.
260TABLE 49CGeneseq Results for NOV49aNOV49aIdentities/Protein/Residues/Similarities forGeneseqOrganism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]Residues/RegionValueAAB93525Human protein sequence SEQ ID1 . . . 578578/584 (98%)0.0NO:12872 - Homo sapiens , 584 aa.1 . . . 584578/584 (98%)[EP1074617-A2, 7 FEB 2001]AAB95663Human protein sequence SEQ ID40 . . . 403 364/370 (98%)0.0NO: 18438 - Homo sapiens, 370 aa.1 . . . 370364/370 (98%)[EP1074617-A2, 7 FEB 2001]AAB93011Human protein sequence SEQ ID1 . . . 407385/470 (81%)0.0NO:11762 - Homo sapiens , 484 aa.1 . . . 470390/470 (82%)[EP1074617-A2, 7 FEB 2001]AAB42049Human ORFX ORF18131 . . . 578306/636 (48%)e−141polypeptide sequence SEQ ID1 . . . 551370/636 (58%)NO:3626 - Homo sapiens, 551 aa.[WO200058473-A2, 5 OCT 2000]AAB95100Human protein sequence SEQ ID1 . . . 578298/636 (46%)e−137NO:17064 - Homo sapiens, 576 aa.1 . . . 576371/636 (57%)[EP1074617-A2, 7 FEB 2001]


[0585] In a BLAST search of public sequence databases, the NOV49a protein was found to have homology to the proteins shown in the BLASTP data in Table 49D.
261TABLE 49DPublic BLASTP Results for NOV49aIdentities/ProteinNOV49aSimilarities forAccessionResidues/Matchthe MatchedExpectNumberProtein/Organism/LengthResiduesPortionValueO95207EPSIN 2A - Homo sapiens1 . . . 578576/584 (98%)0.0(Human), 584 aa.1 . . . 584576/584 (98%)Q9UPT7KIAA1065 PROTEIN - Homo1 . . . 578557/641 (86%)0.0sapiens (Human), 641 aa.1 . . . 641562/641 (86%)O95208EPSIN 2B - Homo sapiens1 . . . 578556/642 (86%)0.0(Human), 642 aa.1 . . . 642560/642 (86%)Q9Z1Z3EH DOMAIN BINDING1 . . . 578512/590 (86%)0.0PROTEIN EPSIN 2 - Rattus1 . . . 583526/590 (88%)norvegicus (Rat), 583 aa.O70447INTERSECTIN-EH BINDING76 . . . 578 438/515 (85%)0.0PROTEIN IBP2 - Mus musculus2 . . . 509459/515 (89%)(Mouse), 509 aa (fragment).


[0586] PFam analysis predicts that the NOV49a protein contains the domains shown in the Table 49E.
262TABLE 49EDomain Analysis of NOV49aIdentities/PfamNOV49aSimilaritiesExpectDomainMatch Regionfor the Matched RegionValueENTH: domain 17 . . . 14070/131(53%)7.9e−681 of 1117/131(89%)VHS: domain 1 of 1 14 . . . 15833/160(21%)3.390/160(56%)UIM: domain 1 of 2217 . . . 23411/18(61%)0.04316/18(89%)UIM: domain 2 of 2242 . . . 2595/18(28%)8012/18(67%)



Example 50

[0587] The NOV50 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 50A.
263TABLE 50ANOV50 Sequence AnalysisSEQ ID NO:1532580 bpNOV50a,ATGCTGCTGGCCCCCTTTTATTGCTGGGTGTGTGCCCATGCTGCTGGCCCCCTTTTATCG59258-01 DNA SequenceTGCTGGGCAGTGACAAACTGTACCATCAGTGGCTCTCCACTGTCCGGAAAGGAAGTGGAGCAATTCTGAATACTGTAAAGACCAAAGCAAATCCGGCCATGAAGACTGTCTACAAGTTCGACATTGCCGAGAATGGCTGCGCCCCCACCCCAGAAGAGCAGCTGCCAAAGACTGCACCGTCCCCACTGGTGGAGGCCAAGGACCCCAAGCTCCGAGAAGACCGGCGGCCAATCACAGTCCACTTTGGACAGGACCAGTCTGAGATGTCTTTCAGCTCAGCACTCACTCACGGCAAAGAGAGTGCCCGGACCCAGCCGGAGAGAGTCGTTGACAGGACTGGCGAGCCCCTGAATCCTGAGCGCGCTCTCTCCGGAGATCATCTCTGGCCTGTTACGCACTTGCTCTGGGCAACCCTGGGCAAGTCCTTGCTTGCCCTCATCTGTGAAATGGGTAGCAGCCCTCGTTCCCTGCAGAGGAGCCTTGCGCTGCTGGGGACACCCCAGCTTATTTGGGAAACTGCAACCACCATGGCCGATGGCCCCACCACGCCCTGTCTAGGAAGCAGAGGCCTCCCCAGCAGCGTGTCCACTGTGCCCCTGGCCCTGCGTGAAGTGCCATCAGATGCCCCGCATCCCTGCAGCAGGGCCCTCGTGACTGGCGTCACAGATGAGGACACAGAGGCCCAGGGAAGTCACTTGCTTGCCAAAGTCACTCAGCAAACCATGTCTGTCTGGCTCTCAGAAAATGGGAAAGAAGCCTGGGCATTCAGCCATGAGGGAGCCACGGCTGTAGCCAGTGGAATGACGTACCCTCAGTCCAGGATGTGCACCCGGGCAGCCAGGTCCCACAGCCACTACTTTCTTGCCCCCACCACTGCTCCCACAGTTCCCAGAACTCAGTCTCCAGATCTGGGCTCCAGGATGCAGAGGCTGTCCTCAGGCCTGGTAAAGCCCTTGCGACACTATGCGGTCTTCCTCTCCGAAGACTCCTCTGATGATGAATGCCAGCGGGAAGAGGGCCCGAGCTCTGGCTTCACCGAGAGCTTTTTCTTCTCCGCTCCCTTTGAATGGCCGCAGCCGTATCGGACACTCAGGGAGTCAGACAGCGCGGAAGGCGACGAGGCAGAGAGTCCAGAGCAGCAAGTGCGGAAGTCCACAGGCCCTGTCCCAGCTCCCCCTGACCGGGCTGCCAGCATCGACCTTCTGGAAGACGTCTTCAGCAACCTGGACATGGAGGCCGCACTGCAGCCACTGGGCCAGGCCAAGAGCTTAGAGGACCTTCGTGCCCCCAAAGACCTGAGGGAGCAGCCAGGGACCTTTGACTATCAGAGGCTGGATCTGGGCGGGAGTGAGAGGAGCCGCGGGGTGACAGTGGCCTTGAAGCTTACCCACCCGTACAACAAGCTCTGGAGCCTGGGCCAGGACGACATGGCCATCCCCAGCAAGCCCCCAGCTGCCTCCCCTGAGAAGCCCTCAGCCCTGCTCGGAAACTCCCTGGCCCTGCCTCGAAGGCCCCAGAACCGGGACAGCATCCTGAACCCCAGTGACAAGGAGGAGGTGCCCACCCCTACTCTGGGCAGCATCACCATCCCCCGGCCCCAAGGCAGGAAGACCCCAGAGCTGGGCATCGTGCCTCCACCGCCCATTCCCCGCCCGGCCAAGCTCCAGGCTGCCGGCGCCGCACTTGGTGACGTCTCAGAGCGGCTGCAGACGGATCGGGACAGGCGAGCTGCCCTGAGTCCAGGGCTCCTGCCTGGTGTTGTCCCCCAAGGCCCCACTGAACTGCTCCAGCCGCTCAGCCCTGGCCCCGGGGCTGCAGGCACGAGCAGTGACGCCCTGCTCGCCCTCCTGGACCCGCTCAGCACAGCCTGGTCAGGCAGCACCCTCCCGTCACGCCCCGCCACCCCGAATGTAGCCACCCCATTCACCCCCCAATTCAGCTTCCCCCCTGCAGGGACACCCACCCCATTCCCACAGCCACCACTCAACCCCTTTGTCCCATCCATGCCAGCAGCCCCACCCACCCTGCCCCTGGTCTCCACACCAGCCGGGCCTTTCGGGGCCCCTCCAGCTTCCCTGGGGCCGGCTTTTGCGTCCGGCCTCCTGCTGTCCAGTGCTGGCTTCTGTGCCCCTCACAGGTCTCAGCCCAACCTCTCCGCCCTCTCCATGCCCAACCTCTTTGGCCAGATGCCCATGGGCACCCACACGAGCCCCCTACAGCCGCTGGGTCCCCCAGCAGTTGCCCCGTCGAGGATCCGAACGTTGCCCCTGGCCCGCTCAAGTGCCAGGGCTGCTGAGACCAAGCAGGGGCTCGCCCTGAGGCCTGGAGACCCCCCGCTTCTGCCTCCCAGGCCCCCTCAAGGCCTGGAGCCAACACTGCAGCCCTCTGCTCCTCAACAGGCCAGAGACCCCTTTGAGGATTTGTTACAGAAAACCAAGCAAGACGTGAGCCCGAGTCCGGCCCTGGCCCCGGCCCCAGACTCGGTGGAGCAGCTCAGGAAGCAGTGGGAGACCTTCGAGTGAORF Start: ATG at 1ORF Stop: TGA at 2578SEQ ID NO:154859 aaMW at 91746.7 kDNOV50a,MLLAPFYCWVCAHAAGPLLLLGSDKLYHQWLSTVRKGSGAILNTVKTKANPAMKTVYKCG59258-01 Protein SequenceFDIAENGCAPTPEEQLPKTAPSPLVEAKDPKLREDRRPITVHFCQDQSEMSFSSALTHGKESARTQPERVVDRTGEPLNPERALSGDHLWPVTELLWATLGKSLLALICEMGSSPRSLQRSLALLGTPQLIWETATTMADGPTTPCLGSRGLPSSVSTVPLALREVPSDAPHPCSRALVTGLTDEDTEAQGSHLLAXVTQQTMSVWLSENGKEAWAFSHEGATAVASGMTYPQSRMCTRAARSHSHYFLAPTTAPTVPRTQSPDLGSRMQRLSSGLVKPLRHYAVFLSEDSSDDECQREEGPSSGFTESFFFSAPFEWPQPYRTLRESDSAEGDEAESPEQQVRKSTGPVPAPPDRAASIDLLEDVFSNLDMEAALQPLGQAKSLEDLRAPKDLREQPGTFDYQRLDLGGSERSRGVTVALKLTHPYNKLWSLGQDDMAIPSKPPAASPEKPSALLGNSLALPRRPQNRNSILNPSDKEEVPTPTLGSITIPRPQGRKTPELGIVPPPPIPRPAKLQAAGAALGDVSERLQTDRDRRAALSPGLLPGVVPQGPTELLQPLSPGPGAAGTSSDALLALLDPLSTAWSGSTLPSRPATPNVATPPTPQFSFPPAGTPTPFPQPPLNPFVPSMPAAPPTLPLVSTPAGPFGAPPASLGPAFASGLLLSSAGFCAPHRSQPNLSALSMPNLFGQMPNGTHTSPLQPLGPPAVAPSRIRTLPLARSSARAAETKQGLALRPGDPPLLPPRPPQGLEPTLQPSAPQQARDPFEDLLQKTKQDVSPSPALAPAPDSVEQLRKQWETFE


[0588] Further analysis of the NOV50a protein yielded the following properties shown in Table 50B.
264TABLE 50BProtein Sequence Properties NOV50aPSort0.4500 probability located in cytoplasm; 0.3000analysis:probability located in microbody (peroxisome);0.1940 probability located in lysosome (lumen);0.1000 probability located in mitochondrial matrix spaceSignalPLikely cleavage site between residues 15 and 16analysis:


[0589] A search of the NOV50a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 50C.
265TABLE 50CGeneseq Results for NOV50aNOV50aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAM41501Human polypeptide SEQ ID NO 22 . . . 103 82/82 (100%)2e−426432-Homo sapiens, 545 aa. 401 . . . 482 82/82 (100%)[WO200153312-A1,26 JUL. 2001]AAM39715Human polypeptide SEQ ID NO 22 . . . 103 82/101 (81%)6e−392860-Homo sapiens, 559 aa. 396 . . . 496 82/101 (81%)[WO200153312-A1,26 JUL. 2001]AAW31855Mycobacterium tuberculosis 55 498 . . . 845 96/358 (26%)8e−12kDa protein-Mycobacterium 71 . . . 389125/358 (34%)tuberculosis, 572 aa.[WO9741252-A2,6 NOV. 1997]AAW31852Mycobacterium tuberculosis 74 498 . . . 845 96/358 (26%)8e−12kDa protein-Mycobacterium 262 . . . 580125/358 (34%)tuberculosis, 763 aa.[WO9741252-A2,6 NOV. 1997]AAB50363Human SRCAP-Homo sapiens, 501 . . . 845112/369 (30%)1e−112972 aa. [WO200073467-A1,1235 . . . 1575141/369 (37%)7 DEC. 2000]


[0590] In a BLAST search of public sequence databases, the NOV50a protein was found to have homology to the proteins shown in the BLASTP data in Table 50D.
266TABLE 59DPublic BLASTP Results for NOV50aNOV50aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueQ9HCG4KIAA1608 PROTEIN-Homo309 . . . 859501/555 (90%)0.0sapiens (Human), 603 aa 62 . . . 603510/555 (91%)(fragment).Q9H796CDNA: FLJ21129 FIS, CLONE 22 . . . 103 81/101 (80%)2e−37CAS06266-Homo sapiens396 . . . 496 81/101 (80%)(Human), 559 aa.AAK44515HYPOTHETICAL 58.5 KDA499 . . . 845104/354 (29%)8e−14PROTEIN-Mycobacterium299 . . . 562121/354 (33%)tuberculosis CDC1551, 598 aa.Q9SN46EXTENSIN-LIKE PROTEIN-604 . . . 848 73/249 (29%)3e−12Arabidopsis thaliana (Mouse-ear407 . . . 626100/249 (39%)cress), 839 aa.Q41805EXTENSIN-LIKE PROTEIN492 . . . 848 88/361 (24%)5e−12PRECURSOR-Zea mays415 . . . 749124/361 (33%)(Maize), 1188 aa.


[0591] PFam analysis predicts that the NOV50a protein contains the domains shown in the Table 50E.
267TABLE 50EDomain Analysis of NOV50aIdentities/PfamNOV50aSimilarities forExpectDomainMatch Regionthe Matched RegionValueNo Significant Matches Found



Example 51

[0592] The NOV51 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 51A.
268TABLE 51ANOV51 Sequence AnalysisSEQ ID NO:1551394 bpNOV51,GTGGCCTGCTCCTGCAGCAATCCCAGGACCCCCTGCTCATGGGGCTGTTTCCTACTAACG59492-01 DNA SequenceCCCCAAAGAGAAGACCCAGGAGGAACCCCCTGGCCAGAGCAGGGCCCCTGTGTTGACCGTGGTGTCCAAGTTCAAGGCCTCACTGGAGCAGCTTCTGCAGGTCCTACACAGCACCACGCCCCACTACATTCGCTGCATCAAGCCCAACAGCCAGGGCCAGGCGCAGACCTTTCTCCAAGAGGAGGTCCTGAGCCAGCTGGAGGCCTGTGGCCTCGTGGAGACCATCCATATCAGTGCTGCTGGCTTCCCCATCCGGGTCTCTCACCGAAACTTTGTAGAACGATACAAGTTACTAAGAAGGCTTCATCCTTGCACATCCTCTGGCCCCGACAGCCCATATCCTGCCAAAGGGCTCCCTGAATGGTGTCCACACAGCGAGGAAGCCACGCTTGAACCTCTCATCCAGGACATTCTCCACACTCTGCCGGTCCTAACTCAGGCAGCAGCCATAACTGGTGACTCGGCTGAGGCCATGCCAGCCCCCATGCACTGTGGCAGGACCAAGGTGTTCATGACTGACTCTATGCTGGAGCTTCTGGAATGTGGGCGTGCCCGGGTGCTGGAGCAGTGTGCCCGCTGCATCCAGGGTGGCTGGAGGCGACACCGGCACCGAGAGCAGGAGCGGCAGTGGCGGGCCGTCATGCTCATCCAGGCAGCCATTCGTTCCTGGTTAACTCGGAAACACATCCAGAGGCTGCATGCAGCTGCCACAGTCATCAAGCGTGCATGGCAGAAGTGGAGAATCAGAATGGCCTGCCTTGCTGCTAAAGAGCTGGATGGTGTGGAAGAAAAACACTTCTCTCAAGCTCCCTGTTCCCTGAGCACCTCGCCGCTGCAGACCAGGCTCCTGGAGGCAATAATCCGCTTCTGGCCCCTGGGACTGGTCCTGGCCAATACGGCTATGGGTGTAGGCAGCTTTCAGAGGAAATTAGTGGTCTGGGCTTGCCTCCAGCTCCCCAGGGGCAGCCCCAGTAGCTACACTGTCCAGACAGCACAAGACCAGGCTGGTGTCACGTCCATCCGAGCGCTGCCTCAGGGATCGATAAAGTTTCACTGCAGAAAGTCTCCACTGCGGTATGCTGACATCTGCCCTGAACCTTCACCCTACAGCATTGCAGGCTTTAATCAGATTCTGCTGGAAAGACACAGGCTGATCCACGTGACCTCTTCTGCCTTCACTGGGCTGGGGTGATCCTTGGTGCCTTTGTTTCCACAAGGCCTTTTCCTGCCCCCTGCCTTGCCAAAGACATTTAATCAGCACACAGCTGCCAGACTATTCCCACAGTGCTCCAAATGCACATGAACAACAGTGACGGCTCCAGCCTTCGACCCAGAGORF Start: ATG at 39ORF Stop: TGA at 1248SEQ ID NO:156403 aaMW at 45142.8 kDNOV51a,MGLFPTNPKEKTQEEPPGQSRAPVLTVVSKFKASLEQLLQVLUSTTPHYIRCIKPNSQCG59492-01 Protein SequenceGQAQTFLQEEVLSQLEACGLVETIHISAAGFPIRVSHRNFVERYKLLRRLHPCTSSGPDSPYPAKGLPEWCPHSEEATLEPLIQDILHTLPVLTQAAAITGDSAEAMPAPMHCGRTKVFMTDSNLELLECGRARVLEQCARCIQGGWRRHRHREQERQWRAVMLIQAAIRSWLTRKHIQRLHAAATVIKRAWQKWRIRMACLAAKELDGVEEKHFSQAPCSLSTSPLQTRLLEAIIRFWPLGLVLANTAMGVGSFQRKLVVWACLQLPRGSPSSYTVQTAQDQAGVTSIRALPQGSIKFIICRKSPLRYADICPEPSPYSIAGFNQILLERHRLIHVTSSAFTGLG


[0593] Further analysis of the NOV51a protein yielded the following properties shown in Table 51B.
269TABLE 51BProtein Sequence Properties NOV51aPSort0.3000 probability located in nucleus; 0.2029 probabilityanalysis:located in lysosome (lumen); 0.1000 probability locatedin mitochondrial matrix space; 00320 probability locatedin microbody (peroxisome)SignalPNo Known Signal Sequence Predictedanalysis:


[0594] A search of the NOV51a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 51C.
270TABLE 51CGeneseq Results for NOV51aNOV51aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAY94290Human myosin heavy chain 1 . . . 403401/403 (99%)0.0homologue-Homo sapiens, 612210 . . . 612401/403 (99%)aa. [WO200026372-A1,11 MAY 2000]AAU23676Novel human enzyme polypeptide 17 . . . 403384/387 (99%)0.0#762-Homo sapiens, 387 aa. 1 . . . 387384/387 (99%)[WO200155301-A2,2 AUG. 2001]ABB10243Human cDNA SEQ ID NO: 551- 1 . . . 365365/365 (100%)0.0Homo sapiens, 570 aa.206 . . . 570365/365 (100%)[WO200154474-A2,2 AUG. 2001]AAU23123Novel human enzyme polypeptide 1 . . . 365364/365 (99%)0.0#209-Homo sapiens, 567 aa.203 . . . 567364/365 (99%)[WO200155301-A2,2 AUG. 2001]AAM23563Human EST encoded protein SEQ 1 . . . 189188/189 (99%)e−108ID NO: 1088-Homo sapiens, 477288 . . . 476188/189 (99%)aa. [WO200154477-A2,2 AUG. 2001]


[0595] In a BLAST search of public sequence databases, the NOV51a protein was found to have homology to the proteins shown in the BLASTP data in Table 5 ID.
271TABLE 51DPublic BLASTP Results for NOV51aNOV51aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueQ96H55HYPOTHETICAL 86.7 KDA 72 . . . 403330/332 (99%)0.0PROTEIN-Homo sapiens (Human)439 . . . 770330/332 (99%)770 aa.Q9D2Z31110055A02R1K PROTEIN 3 . . . 394288/394 (73%) e−162RIKEN CDNA 1110055A02 2 . . . 395320/394 (81%)GENE)-Mus musculus (Mouse),395 aa.Q948A2PUTATIVE MYOSIN HEAVY 2 . . . 255 84/258 (32%)1e−23CHAIN-Oryza sativa (Rice), 1601663 . . . 876125/258 (47%)aa.O74805HYPOTHETICAL MYOSIN- 20 . . . 347 96/340 (28%)1e−21LIKE PROTEIN C2D10.14C IN615 . . . 903152/340 (44%)CHROMOSOME II-Schizosaccharomyces pombe(Fission yeast), 1471 aa.T30148hypothetical protein E02C12.1- 5 . . . 249 74/248 (29%)6e−21Caenorhabditis elegans, 1019 aa.619 . . . 830119/248 (47%)


[0596] PFam analysis predicts that the NOV51a protein contains the domains shown in the Table 51E.
272TABLE 51EDomain Analysis of NOV51aIdentities/PfamNOV51aSimilarities forExpectDomainMatch Regionthe Matched RegionValuemyosin_head: domain 126 . . . 10537/81 (46%)5.1e−25of 160/81 (74%)



Example 52

[0597] The NOV52 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 52A.
273TABLE 52ANOV52 Sequence AnalysisSEQ ID NO:1571380 bpNOV52a,TAGAATTCCAGCGGCCGCTGAAATCCTCACTCGGTCAGTTCCTCGGGCGAGTTACGGGCG59564-01 DNA SequenceGACGACCTGCGGGAGCACGCGGGCAGTGGCCGGACGCTGAAGCCCAGGAGAGCGATGGAGACGTATGCGGAGGTTGGGAAGGAGGGCAAGCCTTCCTGTGCATCGGTGGATCTGCAGGGAGACAGCTCCTTACAGGTGGAGATTTCTCACGCAGTGAGTGAGCGGGACAAGGTGAAATTCACTGTTCAAACAAAGAGCTGCCTCCCTCACTTCGCCCAGACCGAGTTCTCAGTCGTGCGGCAGCACGAGGAGTTCATCTGGCTGCATGATGCCTACGTGGAGAATGAGGAGTACGCCGGCCTCATCATCCCCCCAGCCCCTCCGAGCCCAGACTTTGAGGCTTCGAGGGAAAAGCTACAGAAATTGGGCGAGGGGGACAGCTCTGTCACTCGGGAAGAGTTTGCCAAGATGAAGCAGGAGCTGGAAGCGGAGTACCTGGCCATCTTTAAGAAGACAGTTGCGATGCACGAAGTCTTTCTGCAGCGCCTGGCGGCCCACCCCACCCTGCGTCGAGACCACAACTTCTTTGTGTTTTTGCAATATGGACAGGATCTCAGTGTCCGGGGGAAGAACAGGAAGGAGCTCCTCGGAGGGTTTCTGAGGAATATTGTGAAGTCCGCGGATGAAGCCCTCATCACGGGCATGTCAGGGCTCAAGGAGGTGGATGACTTCTTTGAGCATGAGAGGACCTTCCTGTTGGAGTATCACACCCGTATCCGAGATGCCTGCCTCCGGGCCGACCGCGTCATGCGCGCCCACAAGTGCCTGGCAGACGATTATATCCCTATCTCAGCTGCGCTGAGCAGTCTGGGAACACAGGAAGTCAACCAGCTAAGGACGAGCTTCCTCAAATTGGCACAGCTCTTTGACCGGCTGAGGAAGCTGGAGGGCCGGGTGGCTTCCGATGAGGACCTGAAGCTGTCAGACATGCTGAGGTACTACATGCGTGACTCACAGGCAGCCAAGGACCTGCTGTACCGGCGGCTGCGGGCACTGGCCGACTACGACAATGCCAACAAGGCGCTGCACAAGCCGCGCACCAGGAACCGGGAGGTGCGGCCCGCCGAGAGCCACCAGCAGCTGTGCTGCCAACGCTTCGAGCGCCTCTCCGACTCCGCCAAGCAAGAGCTCATGGACTTCAAGTCCCGCCGGGTCTCCTCTTTTCGAAAGAATCTCATTGAGCTGGCAGAGCTCGAGCTCAAACACGCCAAGGCCAGCACCCTGATTCTCCGGAACACCCTTGTTGCCCTAAAGGGGGAGCCTTAGAGTAGCCAGAGCTCAGCCAGACCCTAATCTGGGATCTCCAGTCACCAGGGTATCCCORF Start: ATG at 113ORF Stop: TAG at 1322SEQ ID NO:158403 aaMW at 46384.2 kDNOV52a,METYAEVGKEGKPSCASVDLQGDSSLQVEISDAVSERDKVKFTVQTKSCLPHFAQTEFCG59564-01 Protein SequenceSVVRQHEEFIWLHDAYVENEEYAGLIIPPAPPRPDFEASREKLQKLGEGDSSVTREEFAKMKQELEAEYLAIFKKTVAMHEVFLQRLAAHPTLRRDHNFFVFLEYGQDLSVRGKNRKELLGGFLRNIVKSADEALITGMSGLKEVDDFFFHERTFLLEYHTRTRDACLRADRVNRAHKCLADDYIPISAALSSLGTQEVNQLRTSFLKLAELFDRLRKLEGRVASDEDLKLSDMLRYYMRDSQAAKDLLYRRLRALADYENANKALDKARTRNREVRPAESEQQLCCQRFERLSDSAKQELMDFKSRRVSSFRKNLIELAELELKHAKASTLILRNTLVALKGEP


[0598] Further analysis of the NOV52a protein yielded the following properties shown in Table 52B.
274TABLE 52BProtein Sequence Properties NOV52aPSort0.6500 probability located in cytoplasm; 0.1000 probabilityanalysis:located in mitochondrial matrix space; 0.1000 probabilitylocated in lysosome (lumen); 0.0000 probability located inendoplasmic reticulum (membrane)SignalPNo Known Signal Sequence Predictedanalysis:


[0599] A search of the NOV52a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 52C.
275TABLE 52CGeneseq Results for NOV52aNOV52aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAY94209Human TRAF four associated factor17 . . . 402273/386 (70%) e−160TFAF2-Homo sapiens, 406 aa.23 . . . 405333/386 (85%)[CA2245340-A1, 19 FEB. 2000]AAB07856Amino acid sequence of Smad117 . . . 402273/386 (70%)1e−160interactor protein clone S1 + 12-2-31 . . . 413333/386 (85%)Homo sapiens, 414 aa.[WO200047102-A2, 17 AUG. 2000]AAB43157Human ORFX ORF292117 . . . 402273/386 (70%) e−160polypeptide sequence SEQ ID77 . . . 459333/386 (85%)NO: 5842-Homo sapiens, 460 aa.[WO200058473-A2, 5 OCT. 2000]AAB58368Lung cancer associated polypeptide17 . . . 402273/386 (70%) e−160sequence SEQ ID 706-Homosapiens, 414 aa. [WO200055180-A2, 21 SEP. 2000]AA013507Human polypeptide SEQ ID NO-17 . . . 400242/384 (63%) e−14427399-Homo sapiens, 443 aa.61 . . . 441317/384 (82%)[WO200164835-A2, 7 SEP. 2001]


[0600] In a BLAST search of public sequence databases, the NOV52a protein was found to have homology to the proteins shown in the BLASTP data in Table 52D.
276TABLE 52DPublic BLASTP Results for NOV52aNOV52aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueQ9UNH7Sorting nexin 6 (TRAF4-associated17 . . . 402273/386 (70%)e−159factor 2)-Homo sapiens (Human),23 . . . 405333/386 (85%)406 aa.Q9CZ032810425K19RIK PROTEIN-Mus17 . . . 402271/386 (70%)e−159musculus (Mouse), 406 aa.23 . . . 405333/386 (86%)Q9Y5X3Sorting nexin 5-Homo sapiens17 . . . 400242/384 (63%)e−143(Human), 404 aa.22 . . . 402317/384 (82%)Q9D8U8Sorting nexin 5-Mus musculus17 . . . 400241/384 (62%)e−142(Mouse), 404 aa.22 . . . 402314/384 (81%)Q96NG4CDNA FLJ30934 FIS, CLONE 1 . . . 237236/237 (99%)e−134FEBRA2007017, MODERATELY 1 . . . 237236/237 (99%)SIMILAR TO HOMO SAPIENSTRAF4-ASSOCIATED FACTOR 2MRNA-Homo sapiens (Human),277 aa.


[0601] PFam analysis predicts that the NOV52a protein contains the domains shown in the Table 52E.
277TABLE 52EDomain Analysis of NOV52aIdentities/PfamNOV52aSimilarities forExpectDomainMatch Regionthe Matched RegionValuePX: domain 1 of 123 . . . 164 39/160 (24%)1.6e−15103/160 (64%)



Example 53

[0602] The NOV53 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 53A.
278TABLE 53ANOV53 Sequence AnalysisSEQ ID NO:1593056 bpNOV53a,CTCCTGCGGGGTCAAATACAGAATTTACGCACCCTTCGCTTCCTTGGAGCCTAGCGGCCG59553-01 DNA SequenceTCTCCCCGCGTCCAAGATGGCGGCAGAAGCAGCTGGTGGGAAATACAGAAGCACAGTCAGCAAAAGCAAAGACCCCTCGGCGCTGCTCATCTCTCTGATCAGGACTCTGTCTACTAGTGACGATGTCGAAGACAGGGAAAATGAAAAGGGTCGCCTTGAAGAAGCCTACGAGAAATGTGACCGTGACCTGGATGAATTGATTGTACAGCACTACACAGAATTGACGACAGCCATTCGCACATACCAGAGCATCACAGAGCGCATCACTAACTCCCGAAATAAAATAAAGCAGGTAAAAGAGAACCTGCTTTCATGCAAGATCCTGCTGCACTGCAAACCGGATGAGCTTCGGAAACTGTGCATTGAAGGAATTGAGCATAAGCATGTCCTGAACTTGTTGGATGAAATTGAGAATATCAAGCAAGTGCCTCAAAAGCTGGAACAGTGCATGGCCAGCAAGCACTATCTCAGTGCCACTGACATGTTGGTGTCAGCAGTTGAGTCTTTGGAGGGCCCCCTGCTCCACGTCGAAGGACTCAGTGACCTTCGACTACAGCTTCACAGCAAGAAGATGAACCTTCACTTGGTTCTCATAGATGAACTACACCGGCACCTGTACATCAAATCGACTAGCCGAGTTGTGCAGCGTAACAAGGAAAAAGGGAAAATCAGCTCCCTCGTGAAACATCCTTCTGTTCCTCTGATTGATGTTACAAACCTCCCTACTCCTCGAAAATTCCTTGATACCTCTCACTATTCTACTGCTGGAAGCTCAAGTGTGAGGGAGATAAATCTGCAGGACATCAAGGAAGATTTAGAATTGGATCCAGAGGAAAACAGCACCCTGTTTATGGGTATCCTCATTAAGGGCTTGGCGAAACTGAAGAAGATCCCAGAAACAGTTAAGGCAATCATAGAGCGCTTGGAGCAGGAGTTGAAGCAAATTCTGAAGAGGTCTACAACCCACGTGCCAGACAGTGGCTATCAGCGGCGGGAGAACGTTACTGTGGAGAACCAACCAAGGTTGCTTCTAGAACTGCTGGAGTTACTGTTTGACAAGTTTAATGCTGTAGCCGCTGCACACTCTGTGGTCCTGGGATACCTGCAGGACACTGTAGTGACTCCACTGACTCAGCAGGAAGATATCAAACTGTATGATATGGCAGATGTATCGGTCAAGATCCAAGATGTTCTACAGATGCTATTAACTCAGTACTTGGATATGAAAAATACTCGTACGGCCTCTGAACCATCAGCTCAACTAAGCTATGCCAGCACTGGACGAGAGTTTGCACCCTTTTTTGCCAAGAACAAACCTCAAACGCCAAAAAATTCTCTTTTCAAGTTCGAATCGTCCTCCCATGCCATCAGTATGAGCGCCTATCTGCGAGAACAGAGAAGGGAGCTCTATAGTCGGAGTGGACAACTCCAAGGCGGTCCTCATGACAACTTAATTGAAGGTGGAGGAACAAAATTTGTCTGCAAACCTGGAGCCAGAAACATTACCGTCATATTCCACCCATTACTAAGATTTATTCAGGAGATTGAGCATGCTCTGCGTCTTGGCCCAGCCAAACAGTGTCCTGTTCGAGAGTTTCTCACCGTGTACATCAAAAACATCTTTCTCAATCAAGTCTTGCCTGAGATCAACAAGCAGATTGAACGAGTCACTAAAACATCTGACCCTTTGAAGATTCTCGCCAACGCACACACCATGAAGGTGCTGGCACTGCAGCGGCCTCTCCTACAGAGCACAATCATTGTGGAGAAGACAGTTCAAGACCTCCTGAACCTGATGCATGACTTGAGTGCATATTCAGATCAATTCCTCAACATGGTGTGCGTGAAGCTCCAGGAGTACAAGGACACCTGCACTGCAGCTTACAGGGGTATTGTCCAGTCAGAAOAAAAACTTGTCATCACTCCATCCTGGGCAAAAGATGATGATATCAGCAGACTCTTGAAATCTCTACCAAACTGGATGAATATGGCTCAACCCAAACAGCTGAGGCCAAAAAGAGAGGAGGAAGAAGATTTCATAAGGGCAGCTTTTGGCAAGGAGTCTGAAGTTCTTATTGGGAACCTGGGTGATAAATTAATCCCTCCACAAGACATCCTTCCTGACCTCAGTGACCTCAAAGCCTTGGCCAACATGCATGAAAGCCTGGAATGCTTGGCAACTCGAACAAAGTCAGCTTTCTCCAATCTTTCTACATCCCAGATGCTTTCTCCTGCTCAAGACAGCCACACGAACACGGATCTCCCCCCAGTGTCAGAGCAGATCATGCAGACTCTCAGTGAACTTGCCAAATCGTTCCAGGATATGGCTGACCGCTGCTTGCTTGTCTTACATCTCGAAGTGACGGTTCACTGTTTCCACTATCTTATCCCTCTTGCAAAGGAGGGGAACTATGCCATTGTGGCTAATGTGGAAAGTATGGATTATGACCCCCTGGTGGTCAAGGTCAACAAAGATATCAGCGCCATTGAAGAGGCCATGAGCGCCAGCCTTCAGCAGCACAAGTTCCAGTATATCTTCGAAGGCCTGGGCCACCTGATCTCCTGCATCCTCATTAATGGTGCCCAGTACTTCAGGCGCATCAGTGAGTCTGGCATCAAGAAAATGTGTAGGAACATTTTTGTTCTTCAGCAGAATTTGACCAACATCACCATGTCGCCGGAGGCAGACCTGGACTTTGCAAGGCAGTACTACGAGATGCTTTACAACACAGCTGACGAGCTCCTGAACCTGGTGGTGGACCAGGGTGTGAAGTACACGGAGCTGGAGTACATCCACGCTCTGACCCTGCTGCACCGCAGCCAGACTGGGGTGGGGGAACTGACCACCCAGAACACGAGCTGCAGAGGAGGCTCAAAGAGATCATCTGCGAGCAGGCTGCCATCAAGCAAGCCACCAAGGACAAGAAGATAACTACCGTTTAGCAGGGCGTACTGCGGTTGGTGACGGGGGTCCCCTCAGTCACACTCACTTTTTTCCORF Start: ATG at 75ORF Stop: TAA at 2988SEQ ID NO:160971 aaMW at 109984.9 kDNOV53a,MAAEAAGGKYRSTVSKSKDPSGLLISVIRTLSTSDDVEDRENEKGRLEEAYEKCDRDLCG59553-01 Protein SequenceDELIVQHYTELTTAIRTYQSITERITNSRNKIKQVKENLLSCKMLLHCKRDELRKLWIEGIEHKHVLNLLDEIENIKQVPQKLEQCMASKHYLSATDMLVSAVESLEGPLLQVEGLSDLRLELHSKKMNLHLVLIDELRRMLYIKSTSRVVQRNKEKGKISSLVRDASVPLIDVTNLPTPRKFLDTSHYSTAGSSSVREINLQDIKEDLELDPEENSTLFMGILIKGLAKLKKIPETVKAITERLEQELKQIVKRSTTQVADSGYQRGENVTVENQPRLLLELLELLFDKFNAVAAAHSVVLGYLQDTVVTPLTQQEDIKLYDMADVWVKIQDVLQMLLTEYLDMKNTRTASEPSAQLSYASTGREFAAFFAKKKPQRPKNSLFKEESSSHAISMSAYLREQRRELYSRSGELQCCPDDNLTECCGTKFVCKPGAPNTTVTFHPLLRFIQETEHALGLCPAKQCPLREFLTVYIKNIFLNQVLAEINKEIEGVTKTSDPLKILANADTMKVLGVQRPLLQSTIIVEKTVQDLLNLMHDLSAYSDQFLNMVCVKLQEYKDTCTAAYRGIVQSEEKLVISASWAKDDDISRLLKSLPNWMNMAQPKQLRPKREEEEDFIRAAFGKESEVLIGNLGDKLIPPQDILRDVSDLKALANMHESLEWLASRTKSAFSNLSTSQMLSPAQDSHTNTDLPPVSEQIMQTLSELAFSFQDMADRCLLVLHLEVRVHCFHYLIPLAKEGNYAIVANVESMDYDPLVVKLNKDISAIEEAMSASLQQHKFQYIFEGLGHLISCILINGAQYFRRISESGIKKMCRNIFVLQQNLTNITMSREADLDFARQYYEMLYNTADELLNLVVDQGVKYTELEYIHALTLLHRSQTGVCELTTQNTSCRCGSKRSSASRLPSSKPPRTRR


[0603] Further analysis of the NOV53a protein yielded the following properties shown in Table 53B.
279TABLE 53BProtein Sequence Properties NOV53aPSort0.5500 probability located in endoplasmic reticulumanalysis:(membrane); 0.1900 probability located in lysosome(lumen); 0.1000 probability located in endoplasmicreticulum (lumen); 0.1000 probability located in outsideSignalPNo Known Signal Sequence Predictedanalysis:


[0604] A search of the NOV53a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 53C.
280TABLE 53CGeneseq Results for NOV53aNOV53aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAB93175Human protein sequence SEQ ID 1 . . . 947947/947 (100%)0.0NO: 12114-Homo sapiens ,974 aa. 1 . . . 947947/947 (100%)[EP1074617-A2, 7 FEB. 2001]AAW69801Amino acid sequence of rsec8, a 1 . . . 947902/948 (95%)0.0protein present in SA-17S 1 . . . 948925/948 (97%)complex-Rattus sp, 975 aa.[WO9828419-A2, 2 JUL. 1998]AAB95143Human protein sequence SEQ ID403 . . . 947545/545 (100%)0.0NO: 17163-Homo sapiens, 572 aa. 1 . . . 545545/545 (100%)[EP1074617-A2, 7 FEB. 2001]AAB58175Lung cancer associated571 . . . 947369/377 (97%)0.0polypeptide sequence SEQ ID 513- 15 . . . 391369/377 (97%)Homo sapiens, 418 aa.[WO200055180-A2,21 SEP. 2000]AAG00950Human secreted protein, SEQ ID451 . . . 544 76/94 (80%)3e−36NO: 5031-Homo sapiens, 100 aa. 7 . . . 100 79/94 (83%)[EP1033401-A2, 6 SEP. 2000]


[0605] In a BLAST search of public sequence databases, the NOV53a protein was found to have homology to the proteins shown in the BLASTP data in Table 53D.
281TABLE 53DPublic BLASTP Results for NOV53aNOV53aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueQ96A65CDNA FLJ14782 FIS, CLONE 1 . . . 947947/947 (100%)0.0NT2RP4000524, HIGHLY 1 . . . 947947/947 (100%)SIMILAR TO MUS MUSCULUSSEC8 MRNA (SECRETORYPROTEIN SEC8)-Homo sapiens(Human), 974 aa.Q9C0G4KIAA1699 PROTEIN-Homo 9 . . . 947939/939 (100%)0.0sapiens (Human), 966 aa 1 . . . 939939/939 (100%)(fragment).O35382SEC8-Mus musculus (Mouse), 971 1 . . . 971923/972 (94%)0.0aa. 1 . . . 971946/972 (96%)Q62824RSEC8-Rattus norvegicus (Rat), 1 . . . 947902/948 (95%)0.0975 aa (fragment). 1 . . . 948925/948 (97%)Q9P102REC8-Homo sapiens (Human),339 . . . 947609/609 (100%)0.0637 aa (fragment). 2 . . . 610609/609 (100%)


[0606] PFam analysis predicts that the NOV53a protein contains the domains shown in the Table 53E.
282TABLE 53EDomain Analysis of NOV53aIdentities/PfamNOV53aSimilarities forExpectDomainMatch Regionthe Matched RegionValueNo Significant Matches Found



Example 54

[0607] The NOV54 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 54A.
283TABLE 54ANOV54 Sequence AnalysisSEQ ID NO:141877 bpNOV54a,CAACACGAGGAACAATGTCTTCTTTACCCGTGCCATACAAACTGCCTGTGTCTTTGTCCG59545-01 DNA SequenceTGTTGGTTCCTGCGTGATAATCAAACCOACACTGATCGACTCTTCTATCAACGAACCACAGCTGCAGGTGGATTTCTACACTGAGATGAATGAGGACTCAGAAATTGCCTTCCATTTGCGAGTGCACTTAGGCCGTCGTGTGGTCATGAACAGTCGTGAGTTTGGGATATGGATGTTGGAGGAGAATTTACACTATGTCCCCTTTGAGGATGGCAAACCATTTCACTTGCGCATCTACGTGTGTCTCAATGAGTATGACGTAAAGGTAAATGGTGAATACATTTATGCCTTTGTCCATCGAATCCCGCCATCATATGTGAAGATGATTCAAGTCTGGAGAGATCTCTCCCTGGACTCAGTGCTTGTCAACAATGGACGGAGATGATCACACTCCTCATTGTTGAGGAAACCCTCTTTCTACCTCACCATCGGATTCCTAGAGCORF Start: ATG at 15ORF Stop: TGA at 441SEQ ID NO:162142 aaMW at 16511.9 kDNOV54a,MSSLPVPYKLPVSLSVGSCVIIKGTLIDSSINEPQLQVDFYTEMNEDSEIAFHLRVILCG59545-01 Protein SequenceGRRVVMNSREFGIWMLEENLHYVPFEDGKPFDLRIYVCLNEYEVKVNGEYIYAFVHRIPPSYVKMTQVWRDVSLDSVLVNNGRR


[0608] Further analysis of the NOV54a protein yielded the following properties shown in Table 54B.
284TABLE 54BProtein Sequence Properties NOV54aPSort0.5500 probability located in endoplasmic reticulumanalysis:(membrane); 0.1900 probability located in lysosome(lumen); 0.1000 probability located in endoplasmicreticulum (lumen); 0.1000 probability locatedin outsideSignalPNo Known Signal Sequence Predictedanalysis:


[0609] A search of the NOV54a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 54C.
285TABLE 54CGeneseq Results for NOV54aNOV54aIdentities/Residues/Similarities forGeneseqProtein/Organism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAG66741Human Charcot-Leyden crystal1 . . . 142139/142 (97%)2e−77protein 5A (CLC5A) - Homo1 . . . 142139/142 (97%)sapiens, 142 aa. [CN1302875-A,11 JUL 2001]AAG66742Human Charcot-Leyden crystal6 . . . 142136/137 (99%)3e−76protein 5B (CLC5B) - Homo34 . . . 170 136/137 (99%)sapiens, 170 aa. [CN1302875-A,11 JUL 2001]AAM79041Human protein SEQ ID NO 1703 -1 . . . 139107/139 (76%)2e−56Homo sapiens, 139 aa.1 . . . 139116/139 (82%)[WO200157190-A2, 09 AUG2001]AAY28350Full Placental Protein 13 amino1 . . . 139107/139 (76%)2e−56acid sequence - Homo sapiens, 1391 . . . 139116/139 (82%)aa. [WO9938970-A1, 5 AUG 1999]AAG78627Human Charcot-Leyden crystal 46 . . . 139102/134 (76%)2e−53CLC4 protein #2 - Homo sapiens,34 . . . 167 111/134 (82%)167 aa. [CN1302876-A, 11 JUL 2001]


[0610] In a BLAST search of public sequence databases, the NOV54a protein was found to have homology to the proteins shown in the BLASTP data in Table 54D.
286TABLE 54DPublic BLASTP Results for NOV54aNOV54aIdentities/ProteinResidues/Similarities forAccessionMatchthe MatchedExpectNumberProtein/Organism/LengthResiduesPortionValueQ9UHV8PLACENTAL PROTEIN 131 . . . 139107/139(76%)9e−56(PLACENTA PROTEIN 13) - Homo1 . . . 139116/139(82%)sapiens (Human), 139 aa.Q9NR03PLACENTAL PROTEIN 13-LIKE1 . . . 13986/139(61%)9e−45PROTEIN - Homo sapiens (Human),1 . . . 139107/139(76%)139 aa.A46523Charcot-Leyden crystal protein -1 . . . 14276/142(53%)7e−36human, 142 aa.1 . . . 14296/142(67%)Q05315Eosinophil lysophospholipase (EC2 . . . 14275/141(53%)3e−353.1.1.5) (Charcot-Leyden crystal1 . . . 14195/141(67%)protein) (Lysolecithin acylhydrolase)(CLC) (Galactin-10) - Homo sapiens(Human), 141 aa.Q96KD6PLACENTAL PROTEIN 13-LIKE -1 . . . 10466/104(63%)1e−31Homo sapiens, (Human), 104 aa1 . . . 10479/104(75%)(fragment).


[0611] PFam analysis predicts that the NOV54a protein contains the domains shown in the Table 54E.
287TABLE 54EDomain Analysis of NOV54aIdentities/SimilaritiesNOV54a Matchfor the MatchedExpectPfam DomainRegionRegionValueGal-bind_lectin:5 . . . 13737/142(26%)3.1e−28domain 1 of 1106/142(75%)



Example 55

[0612] The NOV55 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 55A.
288TABLE 55ANOV55 Sequence AnalysisSEQ ID NO:1632071 bpNOV55a,AAACTATTTTTAGGCGCACTCATGCAGGAAAACCTCAGATTTCCTTCATCAGGAGATGCG59435-01 DNA SequenceATATTAAAATATGGGATGCTTCATCTATCACATTGGTGGATAAATTCAACCCACACACATCACCACATGGAATCAGCTCAATATGTTCGA~CAGCAATAGTAACTTTTTAGTAACAGCATCTTCCAGTGGCGACAAAATAGTTGTCTCAAGTTGCAAATGTAAACCTGTTCCACTTTTAGAGCTTGCTGAAGGGCAAAACCAGACATGTGTCAATTTAAATTCTACATCTATGTATTTGGTAAGCGGAGGCCTAAATAACACTGTTAATATTTGGGATTTAAAATCAAAAAGAGTTCATCGATCTCTTAAGGATCATAAAGATCAAGTAACTTGTGTAACATACAATTGGAATCATTGCTACATTGCTTCTGGATCTCTTAGTGGTGAAATTATTTTACACAGTGTAACCACTAATTTATCTAGTACTCCTTTTGGCCATGGTAGTAACCAGGTTCGGCACTTGAAGTACTCCTTGTTTAAGAAATCACTACTGGGCAGTGTTTCGGATAATGGAATAGTAACTCTCTGGGATGTAAATAGTCAGAGTCCATACCATAACTTTGACAGTGTACACAAAGCTCCAGCGTCAGGCATCTGTTTTTCTCCTGTCAATGAATTGCTCTTTGTAACCATAGGCTTGGATAAAAGAATCATCCTCTAmGACACTTCAAGTAAGAAGCTAGTGAAAACTTTAGTGGCTGACACTCCTCTAACTGCGGTAGATTTCATGCCTGATGCAGCCACTTTGGCTATTGGATCTTCCCGGGGGAAAATATATCAATATGATTTAAGAATGTTGAAATCACCAGTTAAGACCATCAGTCCTCACAAGACATCTGTGCAGTGTATAGCATTTCAGTACTCCACTGTTCTTACTAAGTCAAGTTTAAATAAAGCCTCTTCAAATAACCCCACAACAGTGAACAAACGAAGTGTTAATGTGAATGCTGCTAGTGGAGGAGTTCAGAATTCCGGAATTGTCAGAGAAGCACCTGCCACGTCCATTGCCACAGTTCTACCACAACCTATGACATCAGCTATGGGGAAAGGAACAGTTGCTGTTCAAGAAAAAGCAGGTTTGCCTCGAAGCATAAACACAGACACTTTATCTAAGGAAACAGACAGTGCAAAAAATCAGGATTTCTCCAGCTTTGATGATACTGGGAAAAGTAGTTTAGGTGACATGTTCTCACCTATCAGAGATGATGCTGTAGTTAACAAGGGAAGTGATGAGTCCATAGGCAAAGGAGATGGCTTTGACTTTCTACCGCAGTTGAACTCAGTGTTTCCTCCAACAAAAAATCCAGTAACTTCAAGTACTTCAGTATTGCATTCTAGTCCTCTTAATGTTTTTATGGGATCTCCAGGGAAAGAGGAAAATCAAAACCGTGATCTAACAGCTGAGTCTAAGAAAATATATATCGGAAAACACGAATCTAAACACTCCTTCAAACACTTAGCAAAGTTGGTCACATCTGGTGCTCAAAGTGGAAATCTAAATACCTCTCCATCATCTAACCAAACAAGAAATTCTGAGAAATTTGAAAAGCCAGAGAATGAAATTGAAGCCCAGTTGATATGTGAACCCCCAATCAATCGATCCTCAACTCCAAATCCAAAGATAGCATCTTCTGTCACTGCTGGAGTTGCCAGTTCACTCTCAGAAAAAATAGCCGACAGCATTCCAAATAACCGGCAAAATGCACCATTGACTTCCATTCAAATTCGTTTTATTCAGAACATCATACAGGAAACGTTGGATGACTTTACAGAAGCATGCCATAGCGACATTGTGAATTTGCAAGTGGAGATGATTAAACAGTTTCATATGCAACTCAATGAAATGCATTCTTTGCTGGAAAGATACTCAGTGAATGAAGGTTTAGTGGCTGAAATTGAAAGACTACGAGAAGAAAACAAAACATTACGGGCCCACTTTTGAAATTTCAGTGAATACCTTAATGTTCTGTAATTTGGGAAGTTTCTGGCAACACAGAACTACATAGAATCATORF Start: ATG at 22ORF Stop: TGA at 1999SEQ ID NO:164659 aaMW at 71851.2 kDNOV55a,MQENLRFASSGDDIKTWDASSMTLVDKFNPETSPHGTSSTCWSSNSNFLVTASSSGDKCG59535-01 Protein SequenceIVVSSCKCKPVPLLELAEGQKQTCVNLNSTSMYLVSGCLNNTvNTwDLKSKRVERSLKDHKDQVTCVTYNWNDCYIASGSLSGEITLHSVTTNLSSTFFGHGSNQVRHLKYSLFKKSLLGSVSDNGIVTLWDVNSQSPYHNFDSVHKAPASGICFSPVNELLFVTTGLDKRIILYDTSSKKLVKTLVADTPLTAVDFMPDGATLAIGSSRGKIYQYDLRMLKSPVKTISAHKTSVQCIAFQYSTVLTKSSLNKGCSNKPTTVNKRSVNVNAASGGVQNSCIVREAPATSIATVLPQPMTSAMGKGTVAVQEKAGLPRSINTDTLSKETDSGKNQDFSSFDDTGKSSLGDMFSPIRDDAVVNKGSDESIGKGDGFDFLPQLNSVFPPRKNPVTSSTSVLHSSPLNVFMGSPGKEENENRDLTAESKKIYMGKQESKDSFKQLAKLVTSGAESGNLNTSPSSNQTRNSEKFEKPENEIEAQLICEPPINGSSTPNPKIASSVTAGVASSLSEKIADSIGNNRQNAPLTSIQIRFIQNMIQETLDDFREACHRDIVNLQVEMIKQFHMQLNEMISLLERYSVNEGLVAEIERLREENKRLRAHFSEQ ID NO:1652009 bpNOV55b,AAACTATTTGTAGGCGCAGTCATGCAGGAAAACCTCAGATTTGCTTCATCAGGAGATGCG59435-02 DNA SequenceATATTAAAATATGGGATGCTTCATCTATGACATTGGTGGATAAATTCAACCCACACACATCACCACATGGAATCACCTCAATATGTTGGACCAGCAATAATAACTTTTTAGTAACAGCATCTTCCAGTGGCGACAAAATAGTTGTCTCAAGTTGCAAATGTAAACCTGTTCCACTTTTAGAGCTTGCTGAAGGGCAAAAGCAGACATGTGTCAATTTAAATTCTACATCTATGTATTTGGTAAGCGGAGGCCTAAATAACACTGTTAATATTTGCGATTTAAAATCAAAAAGAGTTCATCGATCTCTTAACGATCATAAAGATCAACTAACTTGTGTAACATACAATTGGAATGATTCCTACATTGCTTCTGGATCTCTTAGTGGTCAAATTATTTTACACAGTGTAACCACTAATTTATCTAGTACTCCTTTTGGCCATGGTAGTAACCAGTCTGTTCGGCACTTGAAGTACTCCTTGTTTAAGAAATCACTACTGGGCAGTGTTTCGGATAATGGAATAGTAACTCTCTGGGATGTAAATAGTCAGAGTCCATACCATAACTTTGACAGTCTACACAAAGCTCCAGCGTCAGGCATCTGTTTTTCTCCTGTCAATGAATTGCTCTTTGTAACCATAGCCTTGGATAAAAGAATCATCCTCTATGACACTTCAAGTAAGAAGCTAGTGAAAACTTTAGTGGCTGACACTCCTCTAACTGCGGTAGATTTCATGCCTGATGGAGCCACTTTGGCTATTGGATCTTCCCGGGGGAAAATATATCAATATGATTTAAGAATGTTGAAATCACCAGTTAAGACCATCAGTGCTCACAAGACATCTGTGCAGTGTATAGCATTTCAGTACTCCACTGTTCTTACTAAGTCAAGTTTAAATAAAOGCTCTTCAAATAAGCCCACAACAGTGAACAAACGAAGTGTTAATCTGAATGCTGCTAGTGGAGGAGTTCAGAATTCCGGAATTGTCAGAGAAGCACCTGCCACGTCCATTGCCACAGTTCTACCACAACCTATGACATCAGCTATGGGGAAACGAACACTTGCTGTTCAAGAAAAAGCAGGTTTGCCTCGAACCATAAACACAGACACTTTATCTAAGGAAACAGACAGTGGAAAAAATCAGGATTTCTCCAGCTTTGATGATACTGGGAAAAGTAGTTTAGGTGACATGTTCTCACCTATCAGAGATGATGCTGTAGTTAACAAGGGAAGTGATGAGTCCATAGGCAAAGGAGATGGCTTTGACTTTCTACCGCAGTTGAACTCAGTGTTTCCTCCAAGAAAAAATCCAGTAACTTCAAGTACTTCAGTATTGCATTCTAGTCCTCTTAATCTTTTTATGGCATCTCCAGGGAAAGAGGAAAATGAAAACCGTGATCTAACAGCTGAGTCTAACAAAATATATATGGGAAAACAGGAATCTAAAGACTCCTTCAAACAGTTAGCAAAGTTGGTCACATCTGGTGCTGAAAGTGGAAATCTAAATACCTCTCCATCATCTAACCAAACAAGAAATTCTGAGAAATTTGAAAAGCCAGAGAATGAAATTGAAGCCCAGTTGATATGTGAACCCCCAATCAATGGATCCTCAACTCCAAATCCAAAGATAGCATCTTCTGTCACTGCTGGAGTTGCCAGTTCACTCTCAGAAAAAATAGCCGACAGCATTGGAAATAACCGGCAAAATGCACCATTGACTTCCATTCAAATTCGTTTTATTCAGAACATGATACAGGAAACGTTGCATCACTTTAGAGAAGCATGCCATAGGGACATTGTGAATTTGCAAGTGGAGATGATTAAACAGTTTCATATGCAACTGAATGAAATGCATTCTTTGCTCGAAAGATACTCAGTGAATGAAGGTTTAGTGGCTGAAATTGAAAGACTACGAGAAGAAAACAAAAGATTACGGGCCCACTTTTGAAATTTORF Start: ATG at 22ORF Stop: TGA at 2002SEQ ID NO:166600 aaMW at 71965.3 kDNOV55b,MQENLRFASSGDDIKIWDASSMTLVDKFNPHTSPHGISSICWSSNNNFLVTASSSGDKCG59435-02 Protein SequenceIVVSSCKCKPVPLLELAEGQKQTCVNLNSTSMYLVSGGLNNTVNIWDLKSKRVHRSLKDHKDQVTCVTYNWNDCYIASGSLSGEIILHSVTTNLSSTPFGHGSNQSVRHLKYSLFKKSLLGSVSDNGIVTLWDVNSQSPYHNFDSVHKAPASGICFSPVNELLFVTICLDKRIILYDTSSKKLVKTLVADTPLTAVDFMPDGATLAIGSSRGKIYQYDLRMIASPVKTISAHKTSVQCIAFQYSTVLTKSSLNXGCSNKPTTVNKRSVNVNAASGGVQNSGIVREAPATSIATVLPQPMTSANGKGTVAVQEKAGLPRSINTDTLSKETDSGKNQDFSSFDDTGKSSLGDMFSPIRDDAVVNKCSDESTGKGDGFDFLPQLNSVFPPRKNPVTSSTSVLHSSPLNVFMGSPGKEENENRDLTAESKKTYMGKQESKDSFKQLAKLVTSGAESGNLNTSPSSNQTRNSEKFEKPENEIEAQLICEPPINGSSTPNPKIASSVTAGVASSLSEKIADSIGNNRQNAPLTSIQIRFIQNNIQETLDDFREACHRDIVNLQVEMIKQFHMQLNEMHSLLERYSVNEGLVAEIERLREENRRLRAHF


[0613] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 55B.
289TABLE 55BComparison of NOV55a against NOV55b.Identities/NOV55a Residues/Similarities for theProtein SequenceMatch ResiduesMatched RegionNOV55b1 . . . 659658/660 (99%)1 . . . 660659/660 (99%)


[0614] Further analysis of the NOV55a protein yielded the following properties shown in Table 55C.
290TABLE 55CProtein Sequence Properties NOV55aPSort0.4500 probability located in cytoplasm; 0.3000analysis:probability located in microbody (peroxisome);0.1000 probability located in mitochondrialmatrix space; 0.1000 probability located inlysosome (lumen)SignalPNo Known Signal Sequence Predictedanalysis:


[0615] A search of the NOV55a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 55D.
291TABLE 55DGeneseq Results for NOV55aIdentities/NOV55aSimilaritiesGeneseqProtein/Organism/LengthResidues/for theExpectIdentifier[Patent #, Date]Match ResiduesMatched RegionValueAAG74568Human colon cancer antigen protein256 . . . 659399/404(98%)0.0SEQ ID NO:5332 - Homo sapiens, 1 . . . 404399/404(98%)404 aa. [WO200122920-A2, 5APR 2001]AAE10677Human NEDD1-related protein -453 . . . 611145/159(91%)4e−75Homo sapiens, 208 aa. 2 . . . 159149/159(93%)[WO200172955-A2, 4 OCT 2001]AAM70774Human bone marrow expressed240 . . . 30667/67(100%)9e−31probe encoded protein SEQ ID NO: 1 . . . 6767/67(100%)31080 - Homo sapiens, 67 aa.[WO200157276-A2, 9 AUG 2001]AAM06190Peptide #4872 encoded by probe for240 . . . 30667/67(100%)9e−31measuring breast gene expression - 1 . . . 6767/67(100%)Homo sapiens, 67 aa.[WO200157270-A2, 9 AUG 2001]ABB23122Protein #5121 encoded by probe for307 . . . 37165/65(100%)3e−29measuring heart cell gene 1 . . . 6565/65(100%)expression - Homo sapiens, 65 aa.[WO200157274-A2, 9 AUG 2001]


[0616] In a BLAST search of public sequence databases, the NOV55a protein was found to have homology to the proteins shown in the BLASTP data in Table 55E.
292TABLE 55EPublic BLASTP Results for NOV55aNOV55aIdentities/ProteinResidues/SimilaritiesAccessionMatchfor theExpectNumberProtein/Organism/LengthResiduesMatched PortionValueI60167regulatory protein Nedd1 - mouse,1 . . . 659564/660(85%)0.0660 aa.1 . . . 660607/660(91%)P33215NEDD1 protein - Mus musculus1 . . . 659564/660(85%)0.0(Mouse), 675 aa (fragment).16 . . . 675 607/660(91%)Q9CWK2NEURAL PRECURSOR CELL1 . . . 659563/660(85%)0.0EXPRESSED,1 . . . 660606/660(91%)DEVELOPMENTALLY DOWN-REGULATED GENE 1 - Musmusculus (Mouse), 660 aa.Q9FI89SIMILARITY TO REGULATORY8 . . . 533145/550(26%)4e−40PROTEIN NEDD1 - Arabidopsis15 . . . 532 246/550(44%)thaliana (Mouse-ear cress), 787 aa.BAB75165WD-40 REPEAT PROTEIN -2 . . . 29892/307(29%)2e−18Anabaena sp. (strain PCC 7120),916 . . . 1208 147/307(46%)1526 aa.


[0617] PFam analysis predicts that the NOV55a protein contains the domains shown in the Table 55F.
293TABLE 55FDomain Analysis of NOV55aIdentities/SimilaritiesNOV55a Matchfor the MatchedExpectPfam DomainRegionRegionValueWD40: domain 1 of 728 . . . 616/37(16%)5727/37(73%)WD40: domain 2 of 7 70 . . . 10510/37(27%)0.06227/37(73%)WD40: domain 3 of 7111 . . . 1479/37(24%)2028/37(76%)WD40: domain 4 of 7153 . . . 19010/38(26%)3.429/38(76%)WD40: domain 5 of 7197 . . . 2347/38(18%)1925/38(66%)WD40: domain 6 of 7240 . . . 27514/37(38%)3.128/37(76%)WD40: domain 7 of 7282 . . . 3168/37(22%)1.3e+0326/37(70%)



Example 56

[0618] The NOV56 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 56A.
294TABLE 56ANOV56 Sequence AnalysisSEQ ID NO:1671771 bpNOV56a,GACTGTTTCACCATGCAGTGGCTAATGAGGTTCCGGACCCTCTGGGGCATCCACAAATCG59439.01 DNA SequenceCCTTCCACAACATCCACCCTGCCCCTTCACAGCTGCGCTCCCGGTCTTTATCAGAATTTGGAGCCCCAAGATGGAATGACTATGAAGTACCGGAGGAATTTAACTTTGCAAGTTATGTACTGGACTACTGCGCTCAAAAGGAGAAGGACGGCAACAGAGGTCCAAATCCAGCTTTTTCGTGGGTGAATGGCCAAGGGGATGAAGTAAAGTGGAGCTTCAGAGAGATGGGAGACCTAACCCGCCGTGTAGCCAACCTCTTCACACAGACCTGTGGCCTACAACAGGGACACCATCTGGCCTTOATGCTGCCTCGAGTTCCTGAGTGGTGGCTCGTGGCTGTGGGCTGCATGCGAACAGGGATCATCTTCATTCCTGCGACCATCCTGTTGAAGGCCAAAGACATTCTCTATCGACTACAGTTGTCTAAAGCCAAGGGCATTGTGACCATAGATGCCCTTGCCTCAGAGGTGGACTCCATAGCTTCTCAGTGCCCCTCTCTGAAAACCAAGCTCCTGGTGTCTGATCACAGCCGTGAAGGGTGGCTGGACTTCCGATCGCTGGTTAAATCAGCATCCCCAGAACACACCTGTGTTAAGTCAAAGACCTTGCACCCAATGGTCATCTTCTTCACCAGTGGGACCACAGGCTTCCCCAAGATGGCAAAACACTCCCATGGGTTGGCCTTACAACCCTCCTTCCCAGGAAGTACGAAATTACGCAGCCTGAAGACATCTGATGTCTCCTGGTGCCTGTCGGACTCAGGATGGATTGTGGCTACCATTTGGACCCTGGTAGAACCATGGACAGCGGGTTGTACAGTCTTTATCCACCATCTGCCACAGTTTGACACCAAGGTCATCATACAGACATTGTTGAAATACCCCATTAACCACTTTTGGGGGGTATCATCTATATATCGAATGATTCTGCAGCAGCATTTCACCACCATCAGGTTCCCTGCCCTGGAGCACTGCTATACTGGCCGGGAGGTCGTGTTGCCCAAGGATCAGGAGGAGTGGAAAAGACGGACCGGCCTTCTGCTCTACGAGAACTATGGGCAGTCGGAAACGGGACTAATTTGTGCCACCTACTGGGGAATGAAGATCAAGCCGGGTTTCATGGGGAAGGCCACTCCACCCTACGACGTCCAGGTCATTGATGACAAGGGCAGCATCCTGCCACCTAACACAGAAGGAAACATTGGCATCAGAATCAAACCTGTCAGGCCTGTGAGCCTCTTCATGTGCTATGAGGGTGACCCAGAGAAGACAGCTAAAGTGGAATGTGGGGACTTCTACAACACTGGGGACAGAGGTAAGATGGATGAAGAGGGCTACATTTGTTTCCTGGGGAGGAGTCATGACATCATTAATGCCTCTGGGTATCGCATCGGGCCTGCAGAGGTTGAAAGCGCTTTGGTGGAGCACCCAGCGGTGGCGGAGTCAGCCGTGGTGGGCAGCCCAGACCCGATTCGAGGGGAGGTGGTGAAGGCCTTTATTGTCCTGACCCCACACTTCCTGTCCCATGACAAGGATCACCTGACCAAGCAACTGCAGCAGCATGTCAAGTCAGTGACAGCCCCATACAAGTACCCAAGGAAGGTGGAGTTTGTCTCAGAGCTGCCAAAAACCATCACTGGCAAGATTGAACCGAACGAACTTCCGAAAAACGAGACTGGTCAGATGTAATCGGCAGTGAACTCAGAACGCACTGORF Start: ATG at 13ORF Stop: TAA at 1744SEQ ID NO:168577 aaMW at 65272.6 kDNOV56a,MQWLMRFRTLWGIHKSFHNIHPAPSQLRCRSLSEFGAPRWNDYEVPEEFNFASYVLDYCG59439-01 Protein SequenceWAQKEKEGKRGPNPAFWWVNGQGDEVKWSFREMGDLTRRVANVFTQTCGLQQGDHLALMLPRVPEWWLVAVGCMRTGIIFIPATILLKAKDILYRLQLSKAKGIVTIDALASEVDSIASQCPSLKTKLLVSDHSREGWLDFRSLVKSASPEHTCVKSKTLDPMVIFFTSGTTGFPKMAKHSHGLALQPSFPGSRKLRSLKTSDVSWCLSDSGWIVATTWTLVEPWTAGCTVFIHHLPQFDTKVIIQTLLKYPINHFWGVSSTYRMILQQDFTSIRFPALEHCYTGGEVVLPKDQEEWKRRTGLLLYENYGQSETGLICATYWGMKIKPGFMGKATPPYDVQVIDDKGSILPPNTEGNTGIRIKPVRPVSLFMCYEGDPEKTAKVECGDFYNTGDRGKMDEEGYICFLGRSDDIINASGYRIGPAEVESALVEHPAVAESAVVGSPDPIRGEVVKAFIVLTPQFLSHDKDQLTKELQQHVKSVTAPYKYPRKVEFVSELPKTITGKIERKELRKKETGQMSEQ ID NO:1691659 bpNOV56b,GTTTCACCATGCAGTCGCTAATCACGTTCCGGACCCTCTGGGGCATCCACAAATCCTTCG59539-02 DNA SequenceCCACAACATCCACCCTGCCCCTTCACAGCTGCGCTGCCGGTCTTTATCAGAATTTGGAGCCCCAACATGGAATGACTATGAAGTACCGGAGGAATTTAACTTTGCAACTTATGTACTGGACTACTGGGCTCAAAAGGAGAAGGAGGGCAAGAGAGGTCCAAATCCAGCTTTTTGGTGCGTGAATCCCCAAGGCGATGAAGTAAAGTGCAGCTTCAGAGAGATGGCAGACCTAACCCGCCGTGTAGCCAACGTCTTCACACAGACCTGTGCCCTACAACAGGCAGACCATCTGGCCTTGATGCTGCCTCGAGTTCCTGAGTGGTGGCTGGTGGCTGTGGGCTGCATGCGAACAGGGATCATCTTCATTCCTGCGACCATCCTGTTGAAGGCCAAAGACATTCTCTATCGACTACAGTTGTCTAAAGCCAAGGCCATTGTGACCATAGATCCCCTTGCCTCAGAGGTGGACTCCATAGCTTCTCAGTGCCCCTCTCTGAAAACCAAGCTCCTGGTGTCTGATCACAGCCGVCAAGGGTGGCTGGACTTCCGATCGCTGGTTAAATCAGCATCCCCAGAACACACCTGTGTTAACTCAAAGACCTTGGACCCAATGGTCATCTTCTTCACCACTGGGACCACAGGCTTCCCCAAGATGGCAAAACACTCCCATGGGTTCGCCTTACAACCCTCCTTCCCAGGAAGTAGGAAATTACGGAGCCTCAAAACATCTGATGTCTCCTGGTGCCTGTCGGACTCACGATGCATTGTGGCTACCATTTGGACCCTGGTAGAACCATGGACAGCGGGTTGTACAGTCTTTATCCACCATCTGCCACAGTTTGACACCAAGGTCATCATACAGACATTGTTGAAATACCCCATTAACCACTTTTGGGGGGTATCATCTATATATCGAATGATTCTGCAGCAGGATTTCACCAGCATCAGGTTCCCTGCCCTGGAGCACTGCTATACTGGCGGGGAGGTCGTGTTGCCCAAGGATCACGAGGAGTCGAAAAGACGGACGGGCCTTCTGCTCTACGAGAACTATCCCCACTCGGAAACGGGACTAATTTGTGCCACCTACTCGGGAATGAAGATCAAGCCGCGTTTCATGGGGAAGGCCACTCCACCCTACGACCTCCAGGGTGACCCAGAGAAGACAGCTAAAGTGGAATGTGGCGACTTCTACAACACTGGGGACAGAGGAAAGATGGATGAAGAGGGCTACATTTGTTTCCTGGGGAGGAGTGATCACATCATTAATGCCTCTGGGTATCGCATCGGGCCTGCAGAGGTTGAAAGTGCTTTGGTGGAGCACCCAGCGGTCGCGGAGTCAGCCGTGGTGGGCAGCCCAGACCCGATTCGAGGGGAGGTGGTGAAGGCCTTTATTGTCCTGACCCCACAGTTCCTGTCCCATGACAAGGATCAGCTGACCAAGGAACTGCAGCAGCATCTCAAGTCAGTGACAGCCCCATACAAGTACCCAAGGAAAGTGGAGTTTGTCTCAGAGCTGCCAAAAACCATCACTGGCAAGATTGAACGGAAGGAACTTCGGAAAAAGGACACTGGTCAGATGTAATCGGCAGTGAACTCAGAACORF Start: ATG at 9ORF Stop: TAA at 1638SEQ ID NO:170543 aaMW at 61518.2 kDNOV56b,MQWLMRFRTLWGIHHSFHNIHPARSQLRCRSLSEFGAPRWNDYEVPEEFNFASYVLDYCG59439-02 Protein SequenceWAQKEKEGKRGPNPAFWWVNGQGDEVKWSFREMGDLTRRVANVFTQTCGLQQGDHLALMLPRVPEWWLVAVGCMRTGIIFIPATILLKAKDILYRLQLSKAKGIVTIDALASEVDSIASQCPSLKTKLLVSDHSREGWLDFRSLVKSASPEHTCVKSKTLDPMVIFFTSGTTCFPKMAKHSHGLALQPSFPGSRKLRSLKTSDVSWCLSDSGWTVATTWTLVEPWTAGCTVFIHHLPQFDTKVIIQTLLKYPINHFWGVSSIYRMILQQDFTSIRFPALEHCYTGGEVVLPKDQEEWKRRTGLLLYENYGQSETGLICATYWGMKIKPGFMGKATPPYDVQGDPEKTAKVECGDFYNTGDRGKMDEEGYICFLGRSDDIINASGYRIGPAEVESALVEHPAVAESAVVGSPDPTRGEVVKAFIVLTPQFLSHDKDQLTKELQQHVKSVTAPYKYPRKVEFVSELPKTTTGKIERKELRKKETCQM


[0619] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 56B.
295TABLE 56BComparison of NOV56a against NOV56b.Identities/NOV56a Residues/Similarities for theProtein SequenceMatch ResiduesMatched RegionNOV56b1 . . . 577543/577 (94%)1 . . . 543543/577 (94%)


[0620] Further analysis of the NOV56a protein yielded the following properties shown in Table 56C.
296TABLE 56CProtein Sequence Properties NOV56aPSort0.6400 probability located in microbody (peroxisome);analysis:0.4712 probability located in mitochondrial matrix space;0.1737 probability located in mitochondrial inner membrane;0.1737 probability located in mitochondrialintermembrane spaceSignalPLike1y cleavage site between residues 23 and 24analysis:


[0621] A search of the NOV56a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 56D.
297TABLE 56DGeneseq Results for NOV56aNOV56aIdentities/Residues/SimilaritiesGeneseqProtein/Organism/LengthMatchfor the ExpectIdentifier[Patent #, Date]ResiduesMatched RegionValueAAB43245Human ORFX ORF3009 46 . . . 573309/529(58%)0.0polypeptide sequence SEQ ID 1 . . . 527402/529(75%)NO:6018 - Homo sapiens, 537 aa.[WO200058473-A2, 5 OCT2000]AAM80008Human protein SEQ ID NO 3654 -331 . . . 577247/279(88%)e−140Homo sapiens, 302 aa. 24 . . . 302247/279(88%)[WO200157190-A2, 9 AUG 2001]AAM80007Human protein SEQ ID NO 3653 -331 . . . 577247/279(88%)e−140Homo sapiens, 302 aa. 24 . . . 302247/279(88%)[WO200157190-A2, 9 AUG 2001]AAM41894Human polypeptide SEQ ID NO257 . . . 573193/317(60%)e−1166825 - Homo sapiens, 390 aa. 7 . . . 323246/317(76%)[WO200153312-A1, 26 JUL 2001]AAM79024Human protein SEQ ID NO 1686 -382 . . . 577196/196(100%)e−112Homo sapiens, 196 aa. 1 . . . 196196/196(100%)[WO200157190-A2, 9 AUG 2001]


[0622] In a BLAST search of public sequence databases, the NOV56a protein was found to have homology to the proteins shown in the BLASTP data in Table 56E.
298TABLE 56EPublic BLASTP Results for NOV56aNOV56aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueQ96A20MIDDLE-CHAIN ACYL-COA1 . . . 577576/577 (99%)0.0SYNTHETASE1 (MEDIUM-1 . . . 577576/577 (99%)CHAIN ACYL-COASYNTHETASE) - Homo sapiens(Human), 577 aa.Q9TVB5XENOBIOTIC/MEDIUM-CHAIN1 . . . 576439/576 (76%)0.0FATTY ACID:COA LIGASE1 . . . 576486/576 (84%)FORM XL-III PRECURSOR - Bostaurus (Bovine), 577 aa.Q9BEA2LIPOATE-ACTIVATING1 . . . 576438/576 (76%)0.0ENZYME PRECURSOR - Bos1 . . . 576485/576 (84%)taurus (Bovine), 577 aa.Q91VA0MEDIUM-CHAIN ACYL-COA1 . . . 577406/577 (70%)0.0SYNTHETASE (EC 6.2.1.2)1 . . . 573472/577 (81%)(HYPOTHETICAL 64.8 KDAPROTEIN) - Mus musculus(Mouse), 573 aa.O70490KIDNEY-SPECIFIC PROTEIN -1 . . . 573315/580 (54%)0.0Rattus norvegicus (Rat), 572 aa.1 . . . 567417/580 (71%)


[0623] PFam analysis predicts that the NOV56a protein contains the domains shown in the Table 56F.
299TABLE 56FDomain Analysis of NOV56aIdentities/SimilaritiesNOV56a Matchfor the MatchedExpectPfam DomainRegionRegionValueAMP-binding:87 . . . 499106/425 (25%)2.5e−96domain 1 of 1299/425 (70%)



Example 57

[0624] The NOV57 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 57A.
300TABLE 57ANOV57 Sequence AnalysisSEQ ID NO:1712501 bpNOV57A,ACACCATGACCACCCTTCATGATAAGTTCCTGGCGGAGAAACTCCAGTACTACTATAGCG59354-01 DNA SequenceCAGCAGTGAGGATGAGGACAGTGACCACCAGGACAAGGACCGAGGCAGATGTGCCCCAGCCAGCAGTTCTGTGCCTGCAGAGGCTGACCTGGCAGCCCAAGGCATCTCAGTTAACACAATGACTCTGAAGGAGTTTGCCATAATGAATGAGGACCAAGATGATGAAGAGTTTCTGCAGCAGTACCCGAAGCAGCGAATGGAAGAGATGCGGCAGCAGCTTCACAAGGGGCCCCAATTCAAGCAAGTTTTTGAGATCTCCAGTGGAGAACGGTTTTTACACATCATTGATAAAGAACAGAAAAGCATTGTCATCATCGTTCATATTTATGAGGATGGCATTCCAGGGACCGAACCCATGAATGGTTGCATGATCTGCCTTGCCGCAGAGTACCCAGCTGTCAAGTTCTGCAAGGTGAAGACCTCACTTATTGCCGCCAGCAGTCAGTTCACCAGGAATGCCCTTCCTGCCCTGCTGATCTATAAGGGGGGTGAATTGATCGGCAATTTTGTTCGTGTTACTGACCAGCTGGGGGATGATTTCTTTGCTGTGCACCTTGAAGCTTTTCTCCAGGAATTTGGATTACTCCCAGAAAAGGAAGTCTTGGTGCTGACATCTGTGCGTAACTCTGCCACGTGTCACAGTGAGGATAGCGACCTGGAAATAGATTGAACTGATAGTCTAGTTGCATAGATTTCTCATTGTTTGGGTTGGAATACACGTCATTCTTTATTTTTGTTCCTTTGTCTTCTGGCTTTTCAGCTGTTCTTTGTAGTCCCTTTTATTATGCATAAAATAAAGAAATTCTTAGATTAAATCAGAATGCTGAATAACCTTGTAGCTAGCAATAAGGTGACTTACAATTGTATAAACAGGAAGCCAGGCTTTTGAACTGTTTACTTAAGATTCTGTGGTGTGACATCTCTGTTATTGTTTCCAGTCAATATTTACAAAGCATCCTAAAGACAGGGTCTTGGAAATTGTCTTCAGATGATCTTAGAGGTCTCTGCCAAGTCTGAGAGTATAATTCTGTAGGTATTGTGTTATTTGCAACGTAAATAGTGCATTTTCTTAATCAAATGATTGTAAATTATATTTACTTGTAATCAGTTCCATAGCTTTAGACGGTGGTTAGATTTTTTTTTTCCCCACCAGGGTCTTGTTTAAAGGGGTCAGCCACCGCACCCAGTCCTGAGGGGTGGCCTCTGCTGCTGGATTTCATGTCTTCCTCCAGCATGACTAACTCTGGAACAGCAGCAAGCGTTGATGCTTACTGACCTGGTGATGTTAGAAGACAAGTAGTTTATGCATTTAAACATTAGAGCTGCAGTGGGGCTGGAAATCTTTGTAAAGGAAGTTCTTTCAGTAAGATGCCCCTGCTTGTCTTTGTCTCTTTTTTGTTTAACAAGGTAACTTTTTGTTTAACAAGGTAACTTTTTGTTTAACCTAGATTTTTTTTAAAACTTTTTTTTTTTTTCATATTGGAAAAGTAATTCATATTCAGTAGAGGAAAACTGACCAAAACAGAAGCAAAAATAAGAAAATTAAAATAATCTCTAATCCTACTACCTAGAATAAAACACTATTAATATTTTGGTCTGTTTCCTGCCAAGGTGTTTTCTGTGTATACATGGATATTTTGTTTGTTTTTAAACAAAACGATGGGATCATTCTGAACATACTGTTCTATAGTATGGTCAGCTAATAATATATCAGACCTTTTTTTTATATTATTAAATATTCTACAACTTTTTAAAAATGTCTATTAATATTCCATCGTATAGATGTGATATAATTTGCTTGATGGTTGTCTCTTAAAAAGAAAGATAGCAAATACTTTTTTTAAATTACAAAAGTGATAGATGTTCATTGTAGAAAATGTAATAAACACTGTTAAGACTTAAAAGCCATATAATTCCACCAACCAAAATTAATCCCTTTTGTCATATTTCTAGTCATTTTTATAGCCTTTTTTTTCTATGTATTTATAATAATTATCATTTGCGTTTTTTTCCTTTTTTTAACTTTAAAAATGTATATTCTAGGGTCAGGGGAAATGTAATCTGGAATTAAATATTAGCCTTAAAATTCACAATTTTGATTTTCCTGGCTTTTCAGGAATTGACTAACTGTAAAAGAGTCTTGAAAGTATTTAGTCAACAAACAGAGTGCATTTTTTTTTTTTTGACTAAGAAAGCTCGTTGTAGTAGAAAGGGTGGAATGTATTGAAAATTATTAGAAGCAGGGAAGTATTGTTAGTCTAGCTTATTTCCTTTCAGTCTTTTTTCAATATTTTTATAAACATTGAGTACTTACTGAATTTAGTTCTGTGCTCTTCCTTATTTAGTGTTGTATCATAAATACTTTGATGTTTCAAACATTCTAATAAATAATTTTCAGTGGCTTCATAATAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAORF Start: ATG at 6ORF Stop: TGA at 726SEQ ID NO:172240 aaMW at 26866.9 kDNOV57a,MTTLDDKLLGEKLQYYYSSSEDEDSDHEDKDRGRCAPASSSVPAEAELAGEGISVNTMCG59354-01 Protein SequenceTLKEFAIMNEDQDDEEFLQQYRKQRMEEMRQQLHKGPQFKQVFEISSGEGFLDMIDKEQKSTVTMVHIYEDGIPGTEANNGCMTCLAAEYPAVKFCKVKSSVIGASSQETRNALPALLIYKGGELIGNFVRVTDQLGDDFFAVDLEAFLQEFGLLPEKEVLVLTSVRNSATCHSEDSDLEIDSEQ ID NO:173893 bpNOV57b,CACCATGACCACCCTGTATGATAAGTTGCTGGGCCAGAAACTGCAGTACTACTATAGCCG59354-02 DNA SequenceAGCAGTGAAGATGAGGACAGTGACCACGAGGACAAGGACCGAGCCATCTCAGTTAACACAGGCCCAAAAGGTGTGATCAATGACTAGCGCCGCTTCAAGCAGTTGGAGACACACCAGAGGGAGGAGCAGTGCCGGGAGATGGAAAGGCTGATCAAGAAGCTGTCAATGACTTGCAGGTCCCATCTGGATGAAGAGGAGGAGCAACAGAAACAGAAAGACCTCCAGGAGAAGATCAGTGGGAACATGACTCTGAAGGAGTTTGCCATAATGAATGAGGACCAACATGATGAAGAGTTTCTGCAGCAGTACCGGAAGCAGCGAATCGAAGAGATGCGGCAGCAGCTTCACAAGCGCCCCCAATTCAAGCAGGTTTTTGAOATCTCCAGTGGAGAAGGGTTTTTAGACATGATTGATAAAGAACAGAAAAGCATTGTCATCATGGTTCATATTTATGAGGATGGCATCAGGGACCGAAGCCATGAATGGTTGCATGATCCCCCTTGCAAGGGGCGTGAATTGATCGGCAATTTTGTTCGTGTTACTGACCAGCTGGGOGATGATTTCTTTGCTGTCGACCTTGAAGCTTTTCTCCAGGAATTTGGATTACTCCCAGAAAAGGAAGTCTTGGTCCTGACATCTGTGCGTAACTCTGCCACGTGTCACAGTGAGGATAGCGACCTGGAAATAGATTGAACTGATAGTCTAGTTGCATATAGATTTCTCATTGTTTGGGTTGGAATACACCATTGTTTATTTTTQTTCCTTTGTCTTCTGGCTTTTCAGCTGTTCTTTGTAGTCCCTTTTATTATGCATAAAATAAAAAAATTCTTAGATTORF Start: ATG at 5ORF Stop: TGA at 749SEQ ID NO:174248 aaMW at 29227.4 kDNOV57b,MTTLYDKLLGEKLQYYYSSSEDEDSDHEDKDRGISVNTGPKGVINDWRRKFQLETEQRCG59354-02 Protein SequenceEEQCREMERLIKKLSMTCRSHLDEEEEQQKQKDLQEKTSGKMTLKEFAIMTEDQDDEEFLQQYRKQRNEEMRQQLHKGPQFKQVFEISSGEGFLDMIDKEQKSIVIMVHIYEDGIRDRSHEWLHDPPCKGGELIGNFVRVTDQLGDDFFAVDLEAFLQEFGLLPEKEVLVLTSVRNSATCHSEDSDLEIDSEQ ID NO:175891 bpNOV57c,CACCATGACCACCCTGTATGATAAGTTGCTGGGGGAGAAACTGCAGTACTACTATAGCCG59354-02 DNA SequenceAGCAGTGAAGATGAGGACAGTGACCACGAGGACAAGGACCGAGGCATCTCAGTTAACACAGGCCCAAAAGGTGTGATCAATGACTGGCGCCGCTTCAAGCAGTTGGAGACAGAGCAGAGGGAGGAGCAGTGCCGGGAGATGGAAAGGCTCATCAAGAAGCTGTCAATGACTTGCAGGTCCCATCTGGATGAAGAGGAGGAGCAACAGAAACAGAAAGACCTCCAGGAGAAGATCAGTGGGAAGATGACTCTGAAGGAGTTTGCCATAATGAATGAGGACCAAGATGATGAAGAGTTTCTGCAGCAGTACCGGAAGCAGCGAATGGAAGAGATGCGGCAGCAGCTTCACAAGGGGCCCCAATTCAAGCAGGTTTTTCAGATCTCCAGTGGAGAAGGGTTTTTAGACATGATTGATAAAGAACAGAAAAGCATTGTCATCATGGTTCATATTTATGAGCATGGCATTCCAGGGACCGAAGCCATGAATGGTTGCATGATCCGCCTTGCCGCAGAGTACCCACCTGTCAAGTTCTGCAAGGTGAAGAGCTCAGTTATTGGCGCCAGCAGTCAGTTCACCAGGAATGCCCTTCCTGCCCTGCTGATCTATAAGGGGGGTGAATTGATCGGCAATTTTGTTCGTGTTACTGACCAGCTGGGGGATGATTTCTTTGCTGTGGACCTTGAAGCTTTTCTCCAGGAATTTGGATTACTCCCAGAAAAGGAAGTCTTGGTGCTGACATCTGTGCGTAACTCTGCCACGTGTCACAGTGAGGATAGCGACCTGGAAATAGATTGAACTGATAGTCTAGTTGCATAGATTTCTCATTGTTTGGGORF Start: ATG at 5ORF Stop: TGA at 851SEQ ID NO:176272 aaMW at 32598.5 kDNOV57c,MTTLYDKLLGEKLQYYYSSSEDEDSDHEDRDRGISVNTGPKGVINDWRRFKQLETEQRCG59354-03 Protein SequenceEEQCREMERLIKKLSMTCRSHLDEEEEQQKQKDLQEKISGKMTLKEFAIMNEDQDDEEFLQQYRKQRMEEMRQQLEKGPQFKQVFETSSGEGFLDMIDKEQKSIVIMVHIYEDGIPGTEAMNGCMIRLAAEYPAVKFCKVKSSVICASSQETRNALPALLIYKGGELIGNFVRVTDQLGDDEFAVDLEAFLQEFGLLPEKEVLVLTSVRNSATCHSEDSDLEID


[0625] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 57B.
301TABLE 57BComparison of NOV57a against NOV57b through NOV57c.Identities/NOV57a Residues/Similarities for theProtein SequenceMatch ResiduesMatched RegionNOV57b 58 . . . 240138/183 (75%)100 . . . 248140/183 (76%)NOV57c 58 . . . 240182/183 (99%)100 . . . 282182/183 (99%)


[0626] Further analysis of the NOV57a protein yielded the following properties shown in Table 57C.
302TABLE 57CProtein Sequence Properties NOV57aPSort0.6500 probability located in cytoplasm; 0.1000 probabilityanalysis:located in mitochondrial matrix space; 0.1000 probabilitylocated in lysosome (lumen); 0.0000 probability located inendoplasmic reticulum (membrane)SignalPNo Known Signal Sequence Predictedanalysis:


[0627] A search of the NOV57a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 57D.
303TABLE 57DGeneseq Results for NOV57aNOV57aIdentities/Protein/Residues/Similarities forGeneseqOrganism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAE03537Human secreted 1 . . . 240226/301 (75%) e−117protein variant, 1 . . . 301230/301 (76%)SEQ ID NO:228—Homosapiens, 301 aa.[WO200132675-A1, May 10,2001]AAY99657Human GTPase 1 . . . 240226/301 (75%) e−117associated 1 . . . 301230/301 (76%)protein-8—Homo sapiens,301 aa.[WO200031263-A2, Jun. 2, 2000]AAE02004Fruitfly viral55 . . . 214 52/161 (32%)3e−14 IAP-associated59 . . . 213 86/161 (53%)factor (VIAF)—Drosophilamelanogaster,240 aa.[WO200134798-A1, May 17,2001]AAE02003Zebrafish viral21 . . . 236 69/241 (28%)5e−13 IAP-associated 2 . . . 237117/241 (47%)factor (VIAF)—Brachydaniorerio, 239 aa.[WO200134798-A1, May 17,2001]AAE02002Mouse viral58 . . . 240 59/195 (30%)4e−12 IAP-associated52 . . . 240 99/195 (50%)factor (VIAF)—Mus musculus,240 aa.[WO200134798-A1, May 17,2001]


[0628] In a BLAST search of public sequence databases, the NOV57a protein was found to have homology to the proteins shown in the BLASTP data in Table 57E.
304TABLE 57EPublic BLASTP Results for NOV57aNOV57aIdentities/ProteinResidues/Similarities forAccessionProtein/Matchthe MatchedExpectNumberOrganism/LengthResiduesPortionValueQ96AF1HYPOTHETICAL1 . . . 240226/301 (75%)e−11734.3 KDA1 . . . 301230/301 (76%)PROTEIN—Homosapiens (Human),301 aa.Q13371Phosducin-like1 . . . 240225/301 (74%)e−116protein (PHLP)—1 . . . 301230/301 (75%)Homo sapiens(Human), 301 aa.T17321hypothetical protein1 . . . 240225/301 (74%)e−116DKFZp564M1863.1—1 . . . 301230/301 (75%)human, 301 aa.Q923E8RIKEN CDNA1 . . . 240210/301 (69%)e−1091200011E13 GENE—1 . . . 301223/301 (73%)Mus musculus(Mouse), 301 aa.Q63737Phosducin-like protein1 . . . 240210/301 (69%)e−108(PHLP)—Rattus1 . . . 301223/301 (73%)norvegicus (Rat),301 aa.


[0629] PFam analysis predicts that the NOV57a protein contains the domains shown in the Table 57F.
305TABLE 57FDomain Analysis of NOV57aIdentities/NOV57aSimilarities forExpectPfam DomainMatch Regionthe Matched RegionValuePhosducin: domain35 . . . 57 14/23 (61%)8.7e−08 1 of 2 21/23 (91%)Phosducin: domain 58 . . . 240133/183 (73%)9.7e−1482 of 2174/183 (95%)



Example 58

[0630] The NOV58 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 58A.
306TABLE 58ANOV58 Sequence AnalysisSEQ ID NO:177756 bpNOV58a,GGATCCCAATGAAGATACAGAATGGAATGACATTTTAAGAGATTTCCGCATTCTTCCTCG59319-01 DNA SequenceCCTAAAGAAGAGTCAAAAGATGAAATTGAAGAAATGGTTTTACGTTTACAGAAAGAAGCAATGGTGAAACCATTTGAAAAGATGACTCTTGCACAGCTAAAGGAAGCTGAAGATGAATTCGATGAAGAAGATATGCAGGCTGTTGAAACATATAGAAAGAAGCGGTTACAGGAATGGAAAGCTCTTAAGAAAAAACAAAAATTTGGACAATTAACAGAAATTTCTGGAAATCAGTATGTGAATGAAGTCACAAATGCAGAAGAAGATGTGTGGGTTATAATTCATCTATACAGATCAAGCATCCCAATGTGTTTGTTGGTTAACCAGCATCTTAGTCTTCTAGCAAGAAAGTTTCCAGAAACTAAATTTGTTAAAGCCATCGTGAATAGCTGTATTCAACACTACCATGACAATTGTTTACCAACAATTTTTGTGTATAAAAATGGTCAGATAGAACCCAAATTCATTGGAATTATAGAATGTGCAOGGATAAATCTCAAGCTGOAAGAACTTGAATGGAAGCTAGCACAACTTGGAGCAATACAGACTCATTTGCAACAAAACCCCACAAAAGACATGGTAGATATGATGGTATCTTCAATTAGAAACACTTCTATTCATGATGACAGTGATAGCTCCAACAGTGATAATGATACCAAATAGAGAGAAATATTCAATAAATAGCTTTTAGTAAAAAAORF Start: GAT at 2ORF Stop: TAG at 719SEQ ID NO:178239 aaMW at 27811.3 kDNOV58a,DPNEDTEWNDILRDFGILPPKEESKDEIEEMVLRLQKEAMVKPFEKMTLAQLKEAEDECG59319-01 Protein SequenceFDEEDMQAVETYRKKRLQEWKALKKKQKFGELREISGHQYVNEVTNAEEDVWVIIHLYRSSIPMCLLVNQHLSLLARKFPETKFVKATVNSCIQHYHDNCLPTTFVYKNGQIEAKFIGIIECGGINLKLEELEWKLAEVGATQTDLEENPRKDMVDMMVSSIRNTSIHDDSDSSNSDNDTKSEQ ID NO:179745 bpNOV58b,GGATCCCAATGAAGATACAGAATGGATCCCAATGAAGATACAGAATGGAATGACATTTCG59319-02 DNA SequenceTAAGACATTTCGGCATTCTTCCTCCTAAAGAAGAGTCAAAAGATGAAATTGAAGAAATGGTTTTACGTTTACAGAAAGAAGCAATGGTGAAACCATTTGAAAAGATGACTCTTGCACAGCTAAAGGAAGCTGAAGATGAATTTGATGAAGAAGATATGCAGGCTGTTGAAACATATAGAAAGAAGCGGTTACAGGAATGGAAACCTCTTAACAAAAAACAAAAATTTGGAGAATTAAGAGAAATTTCTCGAAATCAGTATGTGAATGAAGTCACAAATGCAOAAGAAGATGTGTCGGTTATAATTCATCTATACAGATCAAGCATCCCAATGTGTTTGTTGGTTAACCAGCATCTTAGTCTTCTAGCAAGAAAGTTTCCAGAAACTAAATTTGTTAAAGCCATCGTGAATAGCTGTATTCAACACTACCATGACAATTGTTTACCAACAATTTTTGTGTATAAAAATGCTCACATAGAAGCCAAATTCATTGGAATTATAGAATCTGGAGGGATAAATCTCAAGCTGGAAGAACTTGAATGGAAGCTAGCAGAAGTTGGAGCAATACAGACTGATTTGGAAGAAAACCCCAGAAAACACATCGTAGATATCATGCTATCTTCAATTAGAAACACTTCTATCCATGATGACAGTGATAGCTCCAACAGTGATAATGATACCAAATAGAORF Start: ATG at 22ORF Stop: TAG at 742SEQ ID NO:180240 aaMW at 27942.5 kDNOV58b,MDPNEDTEWNDILRDFCTLPPKEESKDEIEEMVLRLQKEANVKPBERMTLAQLKEAEDCG59319-02 Protein SequenceEFDEEDNQAVETYRKKRLQEWKALKKKQKFGELRETSGNQYVNEVTNAEEDVWVIIHLYRSSIPMCLLVNQHLSLLARKFPETKFVKAIVNSCIQHYHDNCLPTIFVYKNGQIAEKFIGIIECGGINLKLEELEWKLAEVGAIQTDLEENPRKDMVDMMVSSIRNTSIHDDSDSSNSDNDTK


[0631] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 58B.
307TABLE 58BComparison of NOV58a against NOV58b.ProteinNOV58a Residues/Identities/SimilaritiesSequenceMatch Residuesfor the Matched RegionNOV58b1 . . . 239216/239 (90%)2 . . . 240216/239 (90%)


[0632] Further analysis of the NOV58a protein yielded the following properties shown in Table 58C.
308TABLE 58CProtein Sequence Properties NOV58aPSort0.8800 probability located in nucleus; 0.1000 probabilityanalysis:located in mitochondrial matrix space; 0.1000 probabilitylocated in lysosome (lumen); 0.0000 probability located inendoplasmic reticulum (membrane)SignalPNo Known Signal Sequence Predictedanalysis:


[0633] A search of the NOV58a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 58D.
309TABLE 58DGeneseq Results for NOV58aNOV58aIdentities/Protein/Residues/Similarities forGeneseqOrganism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAE02003Zebrafish viral1 . . . 237133/238 (55%)3e−75IAP-associated3 . . . 239181/238 (75%)factor (VIAF)—Brachydanio rerio,239 aa.[WO200134798-A1,May 17, 2001]AAU27979Mouse contig1 . . . 231137/234 (58%)2e−74polypeptide7 . . . 240176/234 (74%)sequence #132—Mus musculus,243 aa.[WO200164834-A2,Sep. 7, 2001]AAU27807Human full-length1 . . . 231137/234 (58%)2e−74polypeptide3 . . . 236176/234 (74%)sequence #132—Mus musculus,239 aa.[WO200164834-A2,Sep. 7, 2001]AAE02001Human viral IAP-1 . . . 231137/234 (58%)2e−74associated factor3 . . . 236176/234 (74%)(VIAF)—Homosapiens, 239 aa.[WO200134798-A1,May 17, 2001]AAB68507Human GTP-1 . . . 231137/234 (58%)2e−74binding associated3 . . . 236176/234 (74%)protein #7—Homo sapiens,239 aa.[WO200105970-A2,Jan. 25, 2001]


[0634] In a BLAST search of public sequence databases, the NOV58a protein was found to have homology to the proteins shown in the BLASTP data in Table 58E.
310TABLE 58EPublic BLASTP Results for NOV58aNOV58aIdentities/ProteinResidues/Similarities forAccessionProtein/Matchthe MatchedExpectNumberOrganism/LengthResiduesPortionValueQ9CQU41700010B22RIK1 . . . 239208/239 (87%) e−121PROTEIN—Mus3 . . . 240229/239 (95%)musculus(Mouse), 240 aa.Q9WUP3PDCL2—Mus1 . . . 239207/239 (86%) e−121musculus1 . . . 238228/239 (94%)(Mouse), 238 aa(fragment).Q9DA991700016K07RIK47 . . . 239 165/193 (85%)3e−94 PROTEIN—Mus1 . . . 192183/193 (94%)musculus(Mouse), 192 aa.CAC40345SEQUENCE 51 . . . 237133/238 (55%)1e−74 FROM PATENT3 . . . 239181/238 (75%)W00134798—Brachydaniorerio (Zebrafish)(Zebra danio),239 aa.Q9H2J4HTPHLP1 . . . 231137/234 (58%)8e−74 (UNKNOWN)3 . . . 236176/234 (74%)(PROTEIN FORMGC:3062)—Homo sapiens(Human), 239 aa.


[0635] PFam analysis predicts that the NOV58a protein contains the domains shown in the Table 58F.
311TABLE 58FDomain Analysis of NOV58aIdentities/NOV58aSimilarities forExpectPfam DomainMatch Regionthe Matched RegionValuePhosducin: domain60 . . . 17532/120 (27%)5.81 of 155/120 (46%)



Example 59

[0636] The NOV59 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 59A.
312TABLE 59ANOV59 Sequence AnalysisSEQ ID NO:181981 bpNOV59a,GCCACCGCGCCCAGCTGGCTTTTGTTTTTTATCCTTCTGCTCCTCATTTACCTATTCACG59576-01 DNA SequenceCCATCATTGGTACTCTTATGCTQTTCTTTGCCATCAAACTGGATTTCTGCCTGCACAGCTCCTTCTATTTCTTCATCACTGTCCTCTCCTTCCTAGAGATCTGGTATACCACCATCACCATCCCCAAGATGTTCTTCAACCTACCCAGTGAGCAGAAGACCACCTCCCTGGATGGTTGCCTATTGCAGATGTATTTCTTTTACTCCCTCGGCATCACTGAGGTTTGCTTGCTCACCACCAGGGCTATGGACACATACCTGGCCATCTGTAATCACCTTTGCTACCCCACAGTCACGACACCTCAGCTCTACACTCAGGTGATTCTAGGTTGTTGCATCTGTGGCTTCTTCACGCTGCTCCCTGAGATTGCTTGGATATCCACACFGCCATTTTGTGGTCCAAATCAAATCCACAACATTTTCTGTGACCTTGATCCTATCCTGAATCTAGCATGTGTAGACACTGGCCCAGTTGTTTTAATCAAGGTTGTGGACATTGTACATGCTGTGGAGATCATCACAGCTATAATGCTTGTGACTTTGCCTTACCTCCAAATTATTGCAGTGATCCTAAGAAACTGCTCTGCTGATCGATGCCAAAAGGCATTTTCTACCTATGCTTTCCACCTTGCTATTTTCTTAATCTTTTTTGGAAGTGTAGCCCTGATGTACCTGCTCTTCTCTGCCAAGTACTCCTTTTTCTGGGACACAACCATCAGCCTAATGTTTGCAGTGCTGTCACCGACAACAATCATCTGTAGTCTCAGGAATAAAGAGATAAAGGAACCAATAAAAAAGCACATGTCCCAATCAATGATATGCACACATCATGTCAAATAAGACCAAATACACACCTCTTAATTACCAAACAATATTTATACAAATATTTACATTAATACGTTCAGTGTGTTTGTTGCTGCTGTGORF Start: GCC at 1ORF Stop: TAA at 895SEQ ID NO:182298 aaMW at 33780.0 kDNOV59a,ATAPSWLLFFTLLLLIYLFTIIGSLMVFFAIKLDFCLHSSFYFFTSVLSFLETWYTTICG59576-01 Protein SequenceTIPKMFFNLASEQKTTSLDGCLLQMYFFYSLGITEVCLLTTRAMDRYLAICNHLCYPTVTTPQLYTQVTLGCCICGFFTLLPETAWISTLPFCGPNQIHNTFCDLDPILNLACVDTGPVVLIKVVDIVHAVEIITAIMLVTLAYVQIIAVILRNCSADGCQKAFSTYAFHLAIFLIFFCSVALMYLLFSAKYSFFWDTTTSLMFAVLSPTTITCSLRNKEIKEATKKHMCQSMICTHHVK


[0637] Further analysis of the NOV59a protein yielded the following properties shown in Table 59B.
313TABLE 59BProtein Sequence Properties NOV59aPSort0.6400 probability located in plasma membrane; 0.4600analysis:probability located in Golgi body; 0.3700 probability locatedin endoplasmic reticulum (membrane); 0.1000 probabilitylocated in endoplasmic reticulum (lumen)SignalPLikely cleavage site between residues 25 and 26analysis:


[0638] A search of the NOV59a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 59C.
314TABLE 59CNOV59aIdentities/Protein/Residues/Similarities forGeneseqOrganism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAG72586Human OR-like 7 . . . 295286/289 (98%) e−167polypeptide query 1 . . . 289286/289 (98%)sequence, SEQID NO: 2267—Homo sapiens,289 aa.[WO200127158-A2, Apr. 19,2001]AAG71784Human olfactory 7 . . . 295286/289 (98%) e−167receptor poly- 1 . . . 289286/289 (98%)peptide, SEQ IDNO: 1465—Homo sapiens,289 aa.[WO200127158-A2, Apr. 19,2001]AAG71785Human olfactory 5 . . . 292175/293 (59%)6e−95 receptor poly-20 . . . 311217/293 (73%)peptide, SEQ IDNO: 1466—Homo sapiens,318 aa.[WO200127158-A2, Apr. 19,2001]AAU24721Human olfactory 7 . . . 283170/279 (60%)4e−94 receptor53 . . . 328212/279 (75%)AOLFR220—Homo sapiens,343 aa.[WO200168805-A2, Sep. 20,2001]AAG71808Human olfactory 7 . . . 283170/279 (60%)4e−94 receptor poly-29 . . . 304212/279 (75%)peptide, SEQ IDNO: 1489—Homo sapiens,317 aa.[WO200127158-A2, Apr. 19,2001]


[0639] In a BLAST search of public sequence databases, the NOV59a protein was found to have homology to the proteins shown in the BLASTP data in Table 59D.
315TABLE 59DPublic BLASTP Results for NOV59aNOV59aIdentities/ProteinResidues/Similarities forAccessionProtein/Matchthe MatchedExpectNumberOrganism/LengthResiduesPortionValueQ96R35OLFACTORY50 . . . 267107/218 (49%)7e−55RECEPTOR— 1 . . . 216146/218 (66%)Homo sapiens(Human), 216 aa(fragment).Q9EPG2M51 OLFACTORY 2 . . . 285115/289 (39%)2e−52RECEPTOR—Mus19 . . . 303172/289 (58%)musculus(Mouse), 314 aa.O95007Olfactory receptor10 . . . 285109/279 (39%)1e−516B1 (Olfactory28 . . . 301170/279 (60%)receptor 7-3)(OR7-3)—Homosapiens (Human),311 aa.Q9QWU6OLFACTORY 1 . . . 289111/298 (37%)2e−50RECEPTOR 17—20 . . . 314171/298 (57%)Mus musculus(Mouse), 327 aa.P23270Olfactory receptor- 1 . . . 289111/298 (37%)2e−50like protein 17—20 . . . 314171/298 (57%)Rattus norvegicus(Rat), 327 aa.


[0640] PFam analysis predicts that the NOV59a protein contains the domains shown in the Table 59E.
316TABLE 59EDomain Analysis of NOV59aIdentities/NOV59aSimilarities forExpectPfam DomainMatch Regionthe Matched RegionValue7tm_1: domain37 . . . 16430/134 (22%)5.4e−131 of 190/134 (67%)



Example 60

[0641] The NOV60 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 60A.
317TABLE 60ANOV60 Sequence AnalysisSEQ ID NO:1831201 bpNOV60aAGGATAACTTTATATGTTGCAAAATGACTCACATAGTATATTTTATTTAACCAGCCTACG59557-1 DNA SequenceATTTCAAGGCTGTTTAGTTGCTTGAAAAGAAGGTTTTTATTTGTTCTTTGCATGTACTTAGAATGCTGACTGTGTTTTATCACCCAACAAGTGAAACCGCTGAAAATATGGATCCAGAGAATCAGACAATGGTGACTGAGTTTTATTTCTCTGATTTTCCTCAATCTAAGAATGGCAGCCTCTTATTCTTCATTCCTATGCTCTTTATTTATATATTCATTCTTGTTGGAAATTTCATGATTTTCTTTGCTGTCCGACCGCACCCCCATCTCCATAATCCTATGTACACTTTTATCAGTGTCTTCTCCTTCCTGGAGATTTGGTACACCACCGTGACTATCCCCAAGATGCTCTCCAACCTTCTCAGTGAACAGAAAACCATCTCTTTCATAGCTTGCCTCCTGCAGATGTACTTCTTCCACTCACTCGGGGTCACAGAAGCCCTAGTCCTCACAGTGATGGCCATTGACAGCTGTGTAGCCATCTGCAACCCCCTTCGCTATGCAATCACTATGTCCCCTAGACTGTGCATCCAGCTCTCCACTGGCTCTTGCATTTTTGGCTTCCTCATGTTACTGCCAGAGATTCTGTGCATTTCCACTCTTCCATTCTGTGGCGCCAACCAAATTCATCAACTCTTTTGTGACTTTGAACCTCTGCTGCAGTTAGCCTGCACAGATACGTACATAATTCTGGTTGAACATGTGATCCGTGCTATTTCCATTCTGACCTCTGTCTCTGTCATCACCCTTTTCTATTTAAGAATCATCACCGTGATCCTGACGATTCCCTCTGGTGAGAGTCGTCACAAGGCTTTCTTCACATGTGCAGCCCACATTGCTATTTTCTTCCTGTTTTTTCGCAGTGTGTCACTCATGTATCTGCGCTTCTCTGTCACATTCCCACCATTACTGGACAAGGCCATTGCACTGATGTTTGCTGTCCTTGCCCTACTTTTCAACCCAGTAATCTATAGTCTGAGGAACAAAGATATCAAAAACGCCACCAAGAAAATCCTCTGTTCTCAAAAGATCTTCAATGCCTCTGGGAGCTAATGGAGTTCACACACACCTCTTCAAAGAAATCTCATCATCTCCTTAAGTTTAAAATGCTAACAAATCAGTTTTTTTAAATTACCATGCAORF Start: ATG at 121ORF Stop: TAA at 1111SEQ ID NO:184330 aaMW at 37439.1 kDNOV60a,MLTVFYEPTSETAENMDPENQTN1VTEFYFSDFPQSKNGSLLFPIPMLFIYIFILVGNFCG59557-01 Protein SequenceMIFFAVRPDPHLHNPMYSFISVFSFLEIWYTTVVTIPKMLSNLLSEQKTISFIGCLLQMYFFHSLGVTEALVLTVMAIDRCVAICNPLRYAITMSPRLCIQLSTGSCIFGFLMLLPEIVCISTLPFCGANQIHQLFCDFEPVLQLACTDTYIILVEDVIRAISILTSVSVITLFYLRITTVILRIPSGESRQKAFFTCAAHIAIELLFFGSVSLMYLRFSVTFPPLLDKAIALMFAVLALLFNPVIYSLRNKDMKNATKKILCSQKMFNASGS


[0642] Further analysis of the NOV60a protein yielded the following properties shown in Table 60B.
318TABLE 60BProtein Sequence Properties NOV60aPSort0.6000 probability located in plasma membrane; 0.4000analysis:probability located in Golgi body; 0.3000 probability locatedin endoplasmic reticulum (membrane); 0.0300 probabilitylocated in mitochondrial inner membraneSignalPLikely cleavage site between residues 67 and 68analysis:


[0643] A search of the NOV60a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 60C.
319TABLE 60CGeneseq Results for NOV60aNOV60aIdentities/Protein/Residues/Similarities forGeneseqOrganism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAG71807Human olfactory16 . . . 330313/315 (99%)e−180receptor poly- 1 . . . 315314/315 (99%)peptide, SEQ IDNO: 1488—Homo sapiens,319 aa.[WO200127158-A2, Apr. 19,2001]AAG71803Human olfactory16 . . . 329219/314 (69%)e−129receptor poly- 1 . . . 314259/314 (81%)peptide, SEQ IDNO: 1484—Homo sapiens,315 aa.[WO200127158-A2, Apr. 19,2001]AAU246581Human olfactory 9 . . . 329218/321 (67%)e−128receptor10 . . . 330259/321 (79%)AOLFR156—Homo sapiens,331 aa.[WO200168805-A2, Sep. 20,2001]AAU24721Human olfactory20 . . . 329196/310 (63%)e−111receptor33 . . . 342234/310 (75%)AOLFR220—Homo sapiens,343 aa.[WO200168805-A2, Sep. 20,2001]AAG71808Human olfactory20 . . . 323195/304 (64%)e−111receptor Homo 9 . . . 312232/304 (76%)sapiens, 317 aa.[WO200127158-A2, Apr. 19,2001]


[0644] In a BLAST search of public sequence databases, the NOV60a protein was found to have homology to the proteins shown in the BLASTP data in Table 60D.
320TABLE 60DPublic BLASTP Results for NOV60aNOV60aIdentities/ProteinResidues/Similarities forAccessionProtein/Matchthe MatchedExpectNumberOrganism/LengthResiduesPortionValueQ9WU86ODORANT15 . . . 324135/315 (42%)4e-67RECEPTOR S1— 8 . . . 320188/315 (58%)Mus musculus(Mouse), 324 aa.Q9EPG2M51 OLFACTORY20 . . . 325129/307 (42%)4e−65RECEPTOR— 5 . . . 311189/307 (61%)Mus musculus(Mouse), 314 aa.P23270Olfactory receptor-24 . . . 319126/301 (41%)8e−65like protein I7—10 . . . 310182/301 (59%)Rattus norvegicus(Rat), 327 aa.Q9QWU6OLFACTORY16 . . . 319128/310 (41%)9e−64RECEPTOR I7— 1 . . . 310184/310 (59%)Mus musculus(Mouse), 327 aa.O13036CHICK16 . . . 319122/305 (40%)1e−63OLFACTORY 1 . . . 305187/305 (61%)RECEPTOR 7—Gallus gallus(Chicken), 323 aa.


[0645] PFam analysis predicts that the NOV60a protein contains the domains shown in the Table 60E.
321TABLE 60EDomain Analysis of NOV60aIdentities/NOV60aSimilarities forExpectPfam DomainMatch Regionthe Matched RegionValue7tm_1: domain56 . . . 204 45/270 (17%)2.4e−211 of 1172/270 (64%)



Example 61

[0646] The NOV61 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 61A.
322TABLE 61ANOV61 Sequence AnalysisSEQ ID NO:1851061 bpNOV61a,CAATCTGCTCCTAAGTCATCTTTTTCTTTTTCACAGGGAAATGGGGGAAAATCAGACACG59555-01 DNA SequenceATGGTCACAGAGTTCCTCCTACTGGGATTTCTCCTGGGCCCAAGGATTCAGATGCTCCTCTTTCGGCTCTTCTCCCTGTTCTATATCTTCACCCTGCTGCGGAACGGGGCCATCCTGGGGCTCATCTCACTGGACTCCAGACTCCACACCCCCATGTACTTCTTCCTCTCACACCTGGCTGTCGTCGACATCGCCTACACCCGCAACACGGTGCCCCAGATGCTGGCGAACCTCCTGCATCCAGCCAAGCCCATCTCCTTTGCTGGCTGCATGACGCAGACCTTTCTCTGTTTGAGTTTTGGACACAGCCAATGTCTCCTGCTGGTGCTGATGTCCTACGATCGTTACGTGGCCATCTGCCACCCTCTCCGATACTCCGTCATCATGACCTGGAGAGTCTGCATCACCCTGGCCGTCACTTCCTCCACCTGTGQCTCCCTCCTGGCTCTGGCCCATGTGGTTCTCATCCTAAGACTCCCCTTCTCTGGGCCTCATCAAATCAACCACTTCTTCTCTGAAATCCTGTCTGTCCTCAGGCTGGCCTGTGCTGACACCTGGCTCAACCAGGTGGTCATCTTTGCAGCCTGCGTGTTCTTCCTGGTGGGGCCACCCAGCCTGGTCCTTGTCTCCTACTCGCACATCCTGGCGGCCATCCTGAGGATCCAGTCTGGGGAGGGCCGCAGAAAGGCCTTCTCCACCTGCTCCTCCCACCTCTGCGTGGTGGGACTCTTCTTTGGCAGTGCCATCATCATGTACATGGCCCCCAAGTCCCGCCATCCTGAGGAGCAGCAAAAGGTCTTTTTTCTATTTTACAGTTTTTTCAACCCAACACTTAACCCCCTGATTTACAGCCTGAGGAACGGAGAGGTCAAGGGTGCCCTGAGGAGAGCACTGGGCAAGGAAAGTCATTCCTAACTGGTCTGACATTTGACTCTCCCTCCTCACTCATCTCCTCGAATCTTGGTACCAAATACCACCTAAGTTCACTACTCTCTTTATATCAORF Start: ATG at 41ORF Stop: TAA at 971SEQ ID NO:186310 aaMW at 34713.8 kDNOV61aMGENQTMVTEFLLLGFLLGPRIQMLLFGLFSLFYIFTLLGNGAILGLISLDSRLHTPMCG59555-01 Protein SequenceYFFLSHLAVVDIAYTRNTVPQMLANLLHPAKPISFAGCMTQTFLCLSFGHSECLLLVLMSYDRYVAICHPLRYSVIMTWRVCITLAVTSWTCGSLLALAHVVLILRLPFSGPHEINHFFCEILSVLRLACADTWLNQVVIFAACVFFLVGPPSLVLVSYSHILAAILRIQSGEGRRKAFSTCSSHLCVVGLFFGSAIIMYMAPKSRHPEEQQKVFFLFYSFFNPTLNPLIYSLRNGEVKGALRRALGKESHS


[0647] Further analysis of the NOV61a protein yielded the following properties shown in Table 61B.
323TABLE 61BProtein Sequence Properties NOV61aPSort0.6400 probability located in plasma membrane; 0.4600analysis:probability located in Golgi body; 0.3700 probability locatedin endoplasmic reticulum (membrane); 0.1000 probabilitylocated in endoplasmic reticulum (lumen)SignalPLikely cleavage site between residues 43 and 44analysis:


[0648] A search of the NOV61a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 61C.
324TABLE 61CGeneseq Results for NOV61aNOV61aIdentities/Protein/Residues/SimilaritiesGeneseqOrganism/LengthMatchfor theExpectIdentifier[Patent #, Date]ResiduesMatched RegionValueAAM29935Peptide #39721 . . . 310310/310 (100%)0.0encoded by probe2 . . . 311310/310 (100%)for measuringplacental geneexpression—Homo sapiens,311 aa.[WO200157272-A2, Aug. 9,2001]AAM17409Peptide #38431 . . . 310310/310 (100%)0.0encoded by probe2 . . . 311310/310 (100%)for measuringcervical geneexpression—Homo sapiens,311 aa.[WO200157278-A2, Aug. 9,2001]AAG72949Human olfactory1 . . . 310310/310 (100%)0.0receptor data2 . . . 311310/310 (100%)explorationsequence, SEQID NO: 2631—Homo sapiens,314 aa.[WO200127158-A2, Apr. 19,2001]AAG72187Human olfactory1 . . . 310310/310 (100%)0.0receptor poly-1 . . . 310310/310 (100%)peptide, SEQ IDNO: 1868—Homo sapiens,310 aa.[WO200127158-A2, Apr. 19,2001]AAU04577Human G-protein1 . . . 310288/310 (92%) e−165coupled receptor1 . . . 308294/310 (93%) like protein,GPCR #11—Homo sapiens,308 aa.[WO200153454-A2, Jul. 26, 2001]


[0649] In a BLAST search of public sequence databases, the NOV61a protein was found to have homology to the proteins shown in the BLASTP data in Table 61D.
325TABLE 61DPublic BLASTP Results for NOV61aNOV61aIdentities/ProteinResidues/SimilaritiesAccessionProtein/Matchfor theExpectNumberOrganism/LengthResiduesMatched PortionValueQ96R46OLFACTORY67 . . . 283217/217 (100%) e−125RECEPTOR— 1 . . . 217217/217 (100%)Homo sapiens(Human), 217 aa(fragment).O95047Olfactory 1 . . . 307217/307 (70%)  e−122receptor 2A4— 1 . . . 307250/307 (80%) Homo sapiens(Human), 310 aa.Q9NQN0DJ1005H11.139 . . . 307187/269 (69%)  e−103(7 TRANS- 1 . . . 269216/269 (79%) MEMBRANERECEPTOR(RHODOPSINFAMILY)(OLFACTORYRECEPTORLIKE)PROTEIN))—Homo sapiens(Human), 272 aa(fragment).Q9Z1V2OLFACTORY63 . . . 285172/223 (77%) 9e−98 RECEPTOR 1 . . . 223190/223 (85%) B12—Musmusculus(Mouse), 223 aa(fragment).O43888OLFACTORY67 . . . 282173/217 (79%) 1e−97 RECEPTOR— 1 . . . 217188/217 (85%) Homo sapiens(Human), 217 aa(fragment).


[0650] PFam analysis predicts that the NOV61a protein contains the domains shown in the Table 61E.
326TABLE 61EDomain Analysis of NOV61aIdentities/NOV61aSimilarities forExpectPfam DomainMatch Regionthe Matched RegionValue7tm_1: domain40 . . . 289 65/269 (24%)1.1e−451 of 1188/269 (70%)



Example 62

[0651] The NOV62 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 62A.
327TABLE 62ANOV62 Sequence AnalysisSEQ ID NO:1871206 bpNOV62a,AGTTGGTTGTAAATAATTCTGCTTATATTACCTACAGAGTAAACATTATAGCATTATCCG59551-1 DNA SequenceACTCCAGAATCCTTTGTTTCTATGGTTTCCACATCTTTCCAATGTCTAGATGTTCCAGCTGCCCATCTCTGACAAATCCACCTGTGTCTCACAATGGATGCCACAGCCTGTAATGAATCAGTGGATGGCTCACCCGTCTTCTATCTATTGGGCATCCCCTCTCTGCCAGAGACCTTCTTCCTCCCTGTGTTTTTTATTTTCCTCCTCTTCTACCTTCTCATCCTGATGGCTAATGCCCTGATCCTGGTGGCCGTGGTGGCAGAGCCCAGCCTCCACAAGCCCATGTACTTCTTTCTGATCAATCTCTCCACCTTCCACATCCTTTTCACCACAACCACTGTCCCCAAGATGCTGTCCTTATTCTTGCTTGCGGACCGCTTCCTCAGCTTTTCTTCCTGCTTACTGCAGATGTACCTCTTCCAAACTTTTACATGTTCAGAAGCCTTCATCCTGGTGGTCATGGCCTATGACCGCTATGTCGCTATCTGCCACCCACTGCACTACCCTGTCCTCATGAACCCACAGACCAATGCTACCTTGGCAGCCAGTGCCTGGCTAACTGCCCTCCTCCTGCCCATCCCAGCACTACTAAGGACCTCCCAGATGGCATATAACAGCATTGCCTACATCTACCACTGCTTCTGTCATCATCTGGCTGTGGTCCAGGCCTCCTGCTCTGACACCACCCCCCAGACCCTCATGGGCTTCTGCATCGCCATGGTGGTGTCCTTCCTCCCCCTTCTCCTGGTGCTTCTCTCCTATGTCCACATCCTGGCCTCAGTGCTTCGCATCAGTTCCCTAGAAGGACGGCCAAAAGCCTTCTCCACCTGCAGCTCCCACCTTCTGGTCGTGGGCACCTACTACTCATCTATTGCCATAGCCTACGTGGCCTACACGGCTGACCTGCCCCTTGACTTCCATATCATGGGCAATGTGGTATATGCCATTCTCACACCAATTCTCAACCCCCTCATTTACACGCTGAGAAACAGCGATGTAAAGGCAGCCATCACCAAAATCATGTCTCAAGACCCACGCTGTGACAGGAGCATTTGACCTTTAAATGCAGCTAACTCTGCTTCCAGGACACCAAATAACAGTGCTTAGCACAGAGAAAGGACTCAATACATGATAATGAAATAAORF Start: ATG at 152ORF Stop: TGA at 1112SEQ ID NO:188320 aaMW at 35502.6 kDNOV62a,MDATACNESVDGSPVFYLLGIPSLPETFFLPVFFIFLLFYLLILMGNALILVAVVAEPCG59551-1 Protein SequenceSLHKPMYFFLINLSTLDILFTTTTVPKMLSLFLLGDRFLSFSSCLLQMYLFQSFTCSEAFILVVMAYDRYVAICHPLHYPVLMNPQTNATLAASAWLTALLLPIPAVVRTSQMAYNSIAYIYHCFCDHLAVVQASCSDTTPQTLMGFCIAMVVSFLPLLLVLLSYVHILASVLRISSLEGRAKAFSTCSSELLVVGTYYSSIAIAYVAYRADLPLDFHIMGNVVYAILTPILNPLIYTLRNRDVKAAITKIMSQDPGCDRSI


[0652] Further analysis of the NOV62a protein yielded the following properties shown in Table 62B.
328TABLE 62BProtein Sequence Properties NOV62aPSort0.6000 probability located in plasma membrane; 0.4000analysis:probability located in Golgi body; 0.3000 probability locatedin endoplasmic reticulum (membrane); 0.3000 probabilitylocated in microbody (peroxisome)SignalPLikely cleavage site between residues 57 and 58analysis:


[0653] A search of the NOV62a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 62C.
329TABLE 62CGeneseq Results for NOV62aNOV62aIdentities/Protein/Residues/Similarities forGeneseqOrganism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAG72119Human olfactory35 . . . 290213/256 (83%) e−119receptor poly- 2 . . . 257228/256 (88%)peptide, SEQ IDNO: 1800—Homo sapiens,295 aa.[WO200127158-A2, Apr. 19,2001]AAU24639Human olfactory16 . . . 308129/293 (44%)6e−67 receptor17 . . . 308186/293 (63%)AOLFR134—Homo sapiens,325 aa.[WO200168805-A2, Sep. 20,2001]AAG72479Human OR-like16 . . . 308129/293 (44%)6e−67 polypeptide query17 . . . 308186/293 (63%)sequence, SEQID NO: 2160—Homo sapiens,324 aa.[WO200127158-A2, Apr. 19,2001]AAG71590Human olfactory16 . . . 308129/293 (44%)6e−67 receptor poly-17 . . . 308186/293 (63%)peptide, SEQ IDNO: 1271—Homo sapiens,324 aa.[WO200127158-A2, Apr. 19,2001]AAG71632Human olfactory16 . . . 315126/300 (44%)3e−64 receptor Homo13 . . . 312179/300 (59%)sapiens, 316 aa.[WO200127158-A2, Apr. 19,2001]


[0654] In a BLAST search of public sequence databases, the NOV62a protein was found to have homology to the proteins shown in the BLASTP data in Table 62D.
330TABLE 62DPublic BLASTP Results for NOV62aNOV62aIdentities/ProteinResidues/Similarities forAccessionProtein/Matchthe MatchedExpectNumberOrganism/LengthResiduesPortionValueQ9Z236OLFACTORY70 . . . 289187/220 (85%) e−104RECEPTOR— 2 . . . 221202/220 (91%)Rattus norvegicus(Rat), 221 aa(fragment).CAB43131OLFACTORY69 . . . 240136/172 (79%)1e−73 RECEPTOR— 1 . . . 172148/172 (85%)Stenellacoeruleoalba(Striped dolphin),172 aa(fragment).Q9EPG2M5116 . . . 310131/295 (44%)2e−67 OLFACTORY12 . . . 305191/295 (64%)RECEPTOR—Mus musculus(Mouse), 314 aa.Q9H208HP416 . . . 312127/297 (42%)3e−65 OLFACTORY12 . . . 308180/297 (59%)RECEPTOR—Homo sapiens(Human), 317 aa(fragment).Q920G5OLFACTORY16 . . . 308126/295 (42%)1e−62 RECEPTOR19 . . . 311180/295 (60%)P3—Musmusculus(Mouse), 324 aa.


[0655] PFam analysis predicts that the NOV62a protein contains the domains shown in the Table 62E.
331TABLE 62EDomain Analysis of NOV62aIdentities/NOV62aSimilarities forExpectPfam DomainMatch Regionthe Matched RegionValue7tm_1: domain46 . . . 295 58/268 (22%)4.6e−381 of 1179/268 (67%)



Example 63

[0656] The NOV63 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 63A.
332TABLE 63ANOV63 Sequence AnalysisSEQ ID NO:1891042 bpNOV63a,GACCTTTCATCACACTCTGGTCATTTACAAACTGTTATTAAGGAATGGGGGACAAGCACG59540-01 DNA SequenceGCCCTGGGTCACAGAATTCATCCTGGTTGGATTCCAGCTCAGTGCAGAGATGGAGATCTTTCTCTCTTGCATCTTCTCCCTGTTATATCTCTTCAGTCTACTGAGGAATGGCATGAACATGGGACTCATCTGTCTGGATCCCAGACTACACACCCCCATATACTTCTTCCTGTCACACTTGGCCGTCATTGACATATACTATGCTTCCAACAATTTGCTCAACATGCTCGAAAACCTAGTGAAACACAAAAAAACTATCTCGTTCATCTCTTGCATTATGCAGATGGCTTTGTATTTGACTTTTGCTGCTGCAGTGTGCATGATTTTGGTGGTGATGTCCTATGACAGATTTGTCGCGATCTGCCATCCCCTGCATTACACTGTCATCATGAACTGGAGAGTGTGCACAGTACTGGCTATTACTTCCTGGGCATCTGCATTTTCCCTGGCCCTCATAAATCTAATTCTCCTTCTAAGGCTGCCCTTCTGTGGGCCCCAGGAGGTGAACCACTTCTTCGGTGAAATTCTGTCTGTCCTCAAACTGGCCTGTGCAGACACCTGGATTAATCAAATTTTTGTCTTTGCTGGTGGTGTGTTTGTCTTAGTCGGGCCCCTTTCCTTGATGCTGATCTCCTACATGCGCATCCTCTTGGCCATCCTGAAGATCCAGTCAGGCGAGGGCCACAGAAAGCACTTCTCTACCTGCTCCTCCCACCTCTGTGTGCTGGCGTTCTTCTTTGCCAACGCCATTGTCATGTACATGGCCCCCAAGTCCCGCCATCCCGAGGAGCAGCAGAAGGTCCTTTCCCTGTTTTGCAGCCTTTCGAATCAGGTGCTGAACCCCCCTCTGATCTACAGCTTGACGAATGCAGAGGTCAAGAGTGCCCCACAAGAGGGCCACTGAAGAAGGAGAGGCTGATGTTACAATCTCAAAGGCACCACGAGGAGAGGGCCTGCTCCGACAAATGGGGAAGTTGGCTTTTTORF Start: ATG at 45ORF Stop: TGA at 960SEQ ID NO:190305 aaMW at 345548 kDNOV63a,MGDKQPWVTEFILVGFQLSAEMEIFLSCIFSLLYLFSLLRNGMNMGLICLDPRLHTPICG59540-1 Protein SequenceYFFLSHLAVIDIYYASNNLLNMLENLVKHKKTISFISCIMQMALYLTFAAAVCMILVVMSYDRFVAICHPLHYTVIMNWRVCTVLAITSWACGFSLALINLILLLRLPFCGPQEVNHFFGEILSVLKLACADTWINEIFVFAGGVFVLVGPLSLMLISYMRTLLAILKIQSGEGHRKDFSTCSSHLCVVGFFFANAIVMYMAPKSRHPEEQQKVLSLFCSLWNQVLNPPLIYSLRNAEVKSAPQEGH


[0657] Further analysis of the NOV63a protein yielded the following properties shown in Table 63B.
333TABLE 63BProtein Sequence Properties NOV63aPSort0.6000 probability located in plasma membrane; 0.4000analysis:probability located in Golgi body; 0.3000 probabilitylocated in endoplasmic reticulum (membrane); 0.3000probability located in microbody (peroxisome)SignalPLikely cleavage site between residues 43 and 44analysis:


[0658] A search of the NOV63a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 63C.
334TABLE 63CGeneseq Results for NOV63aNOV63aIdentities/Protein/Residues/Similarities forGeneseqOrganism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAU24758Human olfactory1 . . . 300258/300 (86%)e−146receptor1 . . . 299275/300 (91%)[WO200168805-A2,Sep. 20, 2001]AAG72952Human olfactory1 . . . 300255/300 (85%)e−144receptor data1 . . . 299272/300 (90%)exploratoriumsequence, SEQ IDNO: 2634—Homo sapiens,310 aa.[WO200127158-A2,Apr. 19, 2001]AAG72377Human OR-like1 . . . 300255/300 (85%)e−144polypeptide query1 . . . 299272/300 (90%)sequence, SEQ IDNO: 2058—Homo sapiens,312 aa.[WO200127158-A2,Apr. 19, 2001]AAG72169Human olfactory1 . . . 300255/300 (85%)e−144receptor poly-1 . . . 299272/300 (90%)peptide, SEQ IDNO: 1850—Homo sapiens,312 aa.[WO200127158-A2,Apr. 19, 2001]AAG71994Human olfactory1 . . . 300225/300 (75%)e−129receptor poly-1 . . . 299256/300 (85%)peptide, SEQ IDNO: 1675—Homo sapiens,314 aa.[WO200127158-A2,Apr. 19, 2001]


[0659] In a BLAST search of public sequence databases, the NOV63a protein was found to have homology to the proteins shown in the BLASTP data in Table 63D.
335TABLE 63DPublic BLASTP Results for NOV63aNOV63aIdentities/ProteinResidues/Similarities forAccessionProtein/Matchthe MatchedExpectNumberOrganism/LengthResiduesPortionValueO95047Olfactory receptor 1 . . . 299173/299 (57%)2e−922A4—Homo 1 . . . 298217/299 (71%)sapiens (Human),310 aa.O43885OLFACTORY67 . . . 281154/216 (71%)5e−88RECEPTOR— 1 . . . 216182/216 (83%)Homo sapiens(Human), 217 aa(fragment).O43888OLFACTORY67 . . . 281153/216 (70%)8e−88RECEPTOR— 1 . . . 216182/216 (83%)Homo sapiens(Human), 217 aa(fragment).Q96R48OLFACTORY67 . . . 281153/216 (70%)2e−87RECEPTOR— 1 . . . 216181/216 (82%)Homo sapiens(Human), 217 aa(fragment).Q96R47OLFACTORY67 . . . 281149/215 (69%)3e−84RECEPTOR— 1 . . . 214175/215 (81%)Homo sapiens(Human), 215 aa(fragment).


[0660] PFam analysis predicts that the NOV63a protein contains the domains shown in the Table 63E.
336TABLE 63EDomain Analysis of NOV63aIdentities/NOV63aSimilarities forExpectPfam DomainMatch Regionthe Matched RegionValue7tm_1: domain47 . . . 290 55/270 (20%)9.7e−251 of 1174/270 (64%)



Example 64

[0661] The NOV64 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 64A.
337TABLE 64ANOV64 Sequence AnalysisSEQ ID NO:191973 bpNOV64a,AGGCACTAAATGAATATCTGTTTAATTCATAAAGTAACAGAGTTTCTCTTCTCTGGATCG59280-01 DNA SequenceTCCCACAGTTTGAAGATGGTAGCCTCCTCTTCTTCATTCCATTGTTTGTTATCTACATATTCATTCTCATTGGGAATCTTATTCTATTTTTTCCACTCAGGGTGGATACCCGTCTCCACAACCCCATGTATAATTTTATCAGCATTTTCTCATTTCTGGAGATCTGGTACACAACTGCCACAATTCCCAAGATGCTCTCCATCCTCATCAGCAGGCAGAGGACCATCTCCATGGTTGGTTGCCTCTTGCAGATGTACTTCTTCCATTCACTGGGAAATTCAGAGGGGATTCAACCATCATGACCCCCGGGCTCTGTGTTCAGCTCTCTGTGGGGTCCTGCATCTTTGGCTTTCTTGTGTTGCTCCCAGAGATTGCATGGATTTCCACACTGCCCTTCTGTGGACCCAACCAAATCCACCAGATCTTCTGTGATTTTGAACCTGTGCTGCGCTTGGCCTGTACAGACACGTCCATGATTCTGATTGAGGATGTGATCCATGCTGTGGCCATTGTATTCTCTGTCCTGATTATTGCCTTTTCTTATATCAGAATCATCACTGTAATCCTGAGGATTCCCTCTGTTGAAGGCCGCCAGAAGGCCTTTTCTACCTGTGCCCCCCATCTTACTGTCTTTCTGATGTTCTATGGCAGTGTATCCCTCATGTACCTGCGTTTCTCTGCCACTTTCCCACCGATTTTGCACACAGCTGTTGCACTGATGTTTGCAGTTCTTGCTCCCTTTTTCAACCCTATCATCTATAGCTTTAGAAATAAGGACATGAAGATTCCAATTAAAAAGCTTTTCTGCCCTCAGAAGATGGTTAATTTATCTGTAGATTAATGCTAGCTCATAGGCAORF Start: ATG at 10ORF Stop: TAA at 955SEQ ID NO:192315 aaMW at 35741.4 kDNOV64a,MNICLIHKVTEFLFSGFPQFEDGSLLFFIPLFVIYIFIVIGNLIVFFAVRVDTRLHNPCG59280-01 Protein SequenceMYNFISIFSFLEIWYTTATIPKMLSILISRQRTISMVGCLLQMYFFHSLGNSEGILLTTMAIDRYVAICNPLRYPTIMTPGLCVQLSVGSCIFGFLVLLPEIAWISTLPFCGPNQIHQIFCDFEPVLRLACTDTSMILTEDVTHAVAIVFSVLIIAFSYIRTTTVTLRTPSVEGRQKAFSTCAAHLSVFLMFYGSVSLMYLRFSATFPPILDTAVALMFAVLAPFFNPIIYSFRNKDMKTAIKKLFCPQKMVNLSVDSEQ ID NO:193929 bpNOV64b,TCTTCTTCATTCCATTGTTTGTTATCTACATATTCATTGTCATTGGGAATCTTATTGTCG59280-02 DNA SequenceATTTTTTGCAGTCAGGGTGGATACCCGTCTCCACAACCCCATGTATAATTTTATCAGCATTTTCTCATTTCTGGAGATCTGGTACACAACTGCCACAATTCCCAAGATGCTCTCCATCCTCATCAGCAGGCAGAGGACCATCTCCATGGTTGGTTGCCTCTTGCAGATGTACTTCTTCCATTCACTGGGAAATTCAGAGGGCATTTTGTTGACCACCATGGCCATTGATAGGTACGTTGCCATCTGTAACCCTCTCCGCTACCCAACCATCATGACCCCCGGGCTCTGTGTTCAGCTCTCTGTGGGGTCCTGCATCTTTGGCTTTCTTGTGTTGCTCCCAGAGATTGCATGGATTTCCACACTGCCCTTCTGTGGACCCAACCAAATCCACCAGATCTTCTGTGATTTTCAACCTGTGCTGCGCTTGGCCTGTACAGACACGTCCATGATTCTGATTGAGGATCTGATCCATGCTGTGGCCATTGTATTCTCTGTCCTGATTATTGCCTTTTCTTATATCAGAATCATCACTGTAATCCTGAGGATTCCCTCTGTTGAAGGCCGCCAGAAGGCCTTTTCTACCTGTCCCGCCCATCTTACTGTCTTTCTGATGTTCTATGGCAGTGTATCCCTCATGTACCTGCGTTTCTCTCCCACTTTCCCACCGATTTTGGACACAGCTGTTGCACTGATGTTTGCAGTTCTTGCTCCCTTTTTCAACCCTATCATCTATAGCTTTACAAATAAGGACATGAAGATTCCAATTAAAAAGCTTTTCTGCCCTCAGAAGATCGTTAATTTATCTGTAGATTAATGCTAGCTCATAGGCACCTTTCACTGTGGATGTTACTCTAACACAATAAACCATATAORF Start: TTC at 3ORF Stop: TAA at 870SEQ ID NO:194289 aaMW at 32772.9 kDNOV64b,FFIPLFVIYIFIVIGNLIVFFAVRVDTRLHNPMYNFISIFSFLEIWYTTATIPKMLSICG59280-02 Protein SequenceLISRQRTISMVGCLLQMYFFHSLGNSEGILLTTMAIDRYVAICNPLRYPTIMTPGLCVQLSVGSCIFGFLVLLPEIAWISTLPFCGPNQIHQIFCDFEPVLRLACTDTSMILIEDVIHAVAIVFSVLIIAFSYTRIITVILRIPSVEGRQKAFSTCAAHLSVFLMFYCSVSLMYLRFSATFPPILDTAVALMFAVLAPFFNPIIYSFRNKDMKIAIKKLFCPQKMVNLSVD


[0662] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 64B.
338TABLE 64BComparison of NOV64a against NOV64b.ProteinNOV64a Residues/Identities/SimilaritiesSequenceMatch Residuesfor the Matched RegionNOV64b27 . . . 315289/289 (100%) 1 . . . 289289/289 (100%)


[0663] Further analysis of the NOV64a protein yielded the following properties shown in Table 64C.
339TABLE 64CProtein Sequence Properties NOV64aPSort0.6000 probability located in plasma membrane; 0.4000analysis:probability located in Golgi body; 0.3000 probabilitylocated in endoplasmic reticulum (membrane); 0.3000probability located in microbody (peroxisome)SignalPLikely cleavage site between residues 54 and 55analysis:


[0664] A search of the NOV64a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 64D.
340TABLE 64DGeneseq Results for NOV64aNOV64aIdentities/Protein/Residues/Similarities forGeneseqOrganism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAG71805Human olfactory59 . . . 314255/256 (99%)e−145receptor poly- 1 . . . 256255/256 (99%)peptide, SEQ IDNO: 1486—Homo sapiens,256 aa.[WO200127158-A2, Apr. 19,2001]AAG71803Human olfactory 9 . . . 311243/303 (80%)e−143receptor SEQ ID 9 . . . 311267/303 (87%)NO: 1484—Homo sapiens,315 aa.[WO200127158-A2, Apr. 19,2001]AAU24658Human olfactory 9 . . . 311240/303 (79%)e−140receptor25 . . . 327264/303 (86%)AOLFR156—Homo sapiens,331 aa.[WO200168805-A2, Sep. 20,2001]AAG71807Human olfactory 9 . . . 313222/305 (72%)e−131receptor poly- 9 . . . 313259/305 (84%)peptide, SEQ IDNO: 1488—Homo sapiens,319 aa.[WO200127158-A2, Apr. 19,2001]AAU24721Human olfactory 9 . . . 308209/300 (69%)e−119receptor37 . . . 336242/300 (80%)AOLFR220—Homo sapiens,343 aa.[WO200168805-A2, Sep. 20,2001]


[0665] In a BLAST search of public sequence databases, the NOV64a protein was found to have homology to the proteins shown in the BLASTP data in Table 64E.
341TABLE 64EPublic BLASTP Results for NOV64aNOV64aIdentities/ProteinResidues/Similarities forAccessionProteinMatchthe MatchedExpectNumberOrganism/LengthResiduesPortionValueQ9EPG2M51 OLFACTORY1 . . . 302137/303 (45%)2e−71RECEPTOR—Mus4 . . . 303194/303 (63%)musculus (Mouse),314 aa.Q9EPV0M50 OLFACTORY6 . . . 302132/298 (44%)3e−71RECEPTOR4 . . . 301191/298 (63%)(OLFACTORYRECEPTORM50)—Musmusculus (Mouse),316 aa.Q9EPG1M50 OLFACTORY6 . . . 302130/298 (43%)2e−70RECEPTOR—4 . . . 301190/298 (63%)Mus musculus(Mouse), 316 aa.Q9WU86ODORANT1 . . . 310133/313 (42%)4e−69RECEPTOR S1—12 . . . 321 190/313 (60%)Mus musculus(Mouse), 324 aa.Q96KK4DJ994E9.59 . . . 314137/307 (44%)9e−68(OLFACTORY2 . . . 306189/307 (60%)RECEPTOR,FAMILY 10,SUBFAMILY C,MEMBER 1(HS6M1-17))—Homo sapiens(Human), 306 aa.


[0666] PFam analysis predicts that the NOV64a protein contains the domains shown in the Table 64F.
342TABLE 64FDomain Analysis of NOV64aIdentities/NOV64aSimilarities forExpectPfam DomainMatch Regionthe Matched RegionValue7tm_1: domain41 . . . 289 51/269 (19%)2.2e−331 of 1179/269 (67%)



Example 65

[0667] The NOV65 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 65A.
343TABLE 65ANOV65 Sequence AnalysisSEQ ID NO:195972 bpNOV65a,GCATGGTGATCCTGTCCTGGGAAAACCAAACGATGAGAGTGGAATTCGTGCTTCAAGGCG59568-01 DNA SequenceATTCTCTTCCATCAGACAGTTAAATATTTTCCTCTTTATGATAATTTTAGTTTTCTACATCTTAACTGTTTCTGCAAACATCCTCATTGTCCTTCTAGTTTTAGTCAGACATCATCTCCACACCCCTATGTACTTCCTCCTGGTGAACTTGTCCTGTCTGGAGATCTGGTATACCTCTAACATCATCCCCAAAATGTTCCTGATTATCATACCTGAAGAGAAGACTATCTCTGTGGCTGGCTGGCTGGCACAATTCTACTTCTTCGGATCCCTGGCTGCCACGGAGTGCCTCTTCCTCACTGTGATGTCCTATGATCGCTACCTAGCCATCTGCCAGCCTCTTTGCTACCGTGTCCTCATGACTGGCCCCCTTTGCATCAGGCTAGCTGCTGGCTCTTGCTTCTGCTGCTTCCTCCTTACAGCAATCACCATGGTCTTGCTATGTAGACTAACCTTCTGTCGACCCTATGAAACTGATCACTTCTTTTGTGACTTCACCCCTCTGCTTCATCTCTCCTGCATGGATACCTCAGTGACTGAGACCATTGCCTTTGCCACCTCTTCTGCAGTAACTCTGATCCCATTTCTCCTCATTGTAGCCTCCTACTCCTCCGTCCTTTCTGCTATCCTAAGAATCCCATCTTGCACAGGCCAGAAAAAGGCCTTCTCCACCTGCTCTTCCCACCTCACTGTGGTCATACTGTTTTATGGGACACTGATTGCCACATACCTTGTGCCCTCAGCCAACTCATCCCAACTCTTGTGCAAAGGGTCCTCTCTGCTCTACATCATCCTGACACCCATGTTTAACCCCATCATTTATAGCCTGAGAAATAGAGACATCCATGAAGCTCTGAAGAACTGCTTGAGGAAGAAGTCAGGTGTTTGCCTTAGATAATACGAAAAGGAAAAAAORF Start: ATG at 3ORF Stop: TAA at 954SEQ ID NO:196317 aa MW at 35713.4 kDNOV65a,MVILSWENQTMRVEFVLQGFSSIRQLNIFLFMIILVFYILTVSGNILIVLLVLVRHHLCG59568-01 Protein SequenceHTPMYFLLVNLSCLETWYTSNYTPKMLLIIIAEEKTISVAGWLAQFYFFGSLAATECLLLTVMSYDRYLATCQPLCYRVLNITGPLCIRLAAGSWFCCFLLTAITMVLLCRLTFCGPYETDHFFCDFTPLVHLSCMDTSVTETTAFATSSAVTLTPFLLIVASYSCVLSATLRIPSCTGQKKAFSTCSSHLTVVIVFYGTLIATYLVPSANSSQLLCKGSSLLYIILTPMFNPIIYSLRDIHEALKKCLRKKSGVCLR


[0668] Further analysis of the NOV65a protein yielded the following properties shown in Table 65B.
344TABLE 65BProtein Sequence Properties NOV65aPSort0.6000 probability located in plasma membrane; 0.4000analysis:probability located in Golgi body; 0.3888 probability locatedin mitochondrial inner membrane; 0.3030 probability locatedin mitochondrial intermembrane spaceSignalPLikely cleavage site between residues 45 and 46analysis:


[0669] A search of the NOV65a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 65C.
345TABLE 65CGeneseq Results for NOV65aNOV65aIdentities/Protein/Residues/Similarities forGeneseqOrganism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAG72527Human OR-like1 . . . 316315/316 (99%)0.0polypeptide query1 . . . 316315/316 (99%)sequence, SEQ IDNO: 2208—Homo sapiens,316 aa.[WO200127158-A2, Apr. 19,2001]AAG72231Human olfactory1 . . . 316315/316 (99%)0.0receptor poly-1 . . . 316315/316 (99%)peptide, SEQ IDNO: 1912—Homo sapiens,316 aa.[WO200127158-A2, Apr. 19,2001]AAG72084Human olfactory1 . . . 316315/316 (99%)0.0receptor poly-1 . . . 316315/316 (99%)peptide, SEQ IDNO: 1765—Homo sapiens,316 aa.[WO200127158-A2, Apr. 19,2001]AAG72700Murine OR-like1 . . . 308154/308 (50%)2e−83polypeptide query3 . . . 308208/308 (67%)sequence, SEQ IDNO: 2382—Musmusculus, 314 aa.[WO200127158-A2, Apr. 19,2001]AAG71814Human olfactory8 . . . 311142/304 (46%)7e−79receptor poly-5 . . . 308208/304 (67%)peptide, SEQ IDNO: 1495—Homo sapiens,317 aa.[WO200127158-A2, Apr. 19,2001]


[0670] In a BLAST search of public sequence databases, the NOV65a protein was found to have homology to the proteins shown in the BLASTP data in Table 65D.
346TABLE 65DPublic BLASTP Results for NOV65aNOV65aIdentities/ProteinResidues/Similarities forAccessionProteinMatchthe MatchedExpectNumberOrganism/LengthResiduesPortionValueQ9GZK7Olfactory receptor1 . . . 308147/308 (47%)4e−7711A1 (Hs6M1-1 . . . 306202/308 (64%)18)—Homosapiens (Human),315 aa.O13036CHICK7 . . . 311139/305 (45%)1e−76OLFACTORY4 . . . 308198/305 (64%)RECEPTOR 7—Gallus gallus(Chicken), 323 aa.Q9JKA6OLFACTORY4 . . . 313143/311 (45%)1e−75RECEPTOR P2—1 . . . 311194/311 (61%)Mus musculus(Mouse), 315 aa.Q9WU86ODORANT14 . . . 308 144/295 (48%)2e−75RECEPTOR S1—21 . . . 315 189/295 (63%)Mus musculus(Mouse), 324 aa.Q9UGF6Olfactory receptor7 . . . 305138/299 (46%)5e−755V1 (Hs6M1-21)—4 . . . 302199/299 (66%)Homo sapiens(Human), 321 aa.


[0671] PFam analysis predicts that the NOV65a protein contains the domains shown in the Table 65E.
347TABLE 65EDomain Analysis of NOV65aIdentities/NOV65aSimilarities forExpectPfam DomainMatch Regionthe Matched RegionValuegranulin: domain144 . . . 155  7/13 (54%)1.71 of 1 11/13 (85%)Trypan_glycop:218 . . . 241  6/24 (25%)7.9domain 1 of 1 21/24 (88%)7tm_1: domain 44 . . . 293 53/268 (20%)1.5e−311 of 1172/268 (64%)



Example 66

[0672] The NOV66 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 66A.
348TABLE 66ANOV66 Sequence AnalysisSEQ ID NO:197987 bpNOV66a,CATCTTCCTATGTGTCATGTCTCCTCTTAATGACACAAAAATGGAAGTCCTTAGATTCCG59224-01 DNA SequenceCTCCTTATCGGGATCACTGGACTGGAGAAAAGTCGCACCTGGATATCCATTCCTTTCTTATCTGTGTACCTTCTTTCTTGGATGCCTAATTTTACCGTCCTCTTTTTTATCAAGACAGACCAAAGCCTCCATGAACCTATGTATTATTTGCTTTCCATGCTCTCCATCTCTGACCTACGGCTGTCTCTGTCTTCCTTACCCATCACTTTGGGACTATTCCTATTTGATGTCCATGAAATTCATGCAGCTCCATGCTTTGCCCAGGAATTTTTTATCCATCTGTTTACACTCAGTGAAGCCTCTGTACTGTCTGTAATGGCATTTGACTGGTATGTGGCAATCCACAGTCCTTTGAGATACAGCACTATCTTAACTAGTCCCAGAGCCATCAAAACAGGGGTTCTTCTGACTTCCAAGAATGTTCTTTTGATCCTTCCACTGCCCTTTCTCTTGCAAAGGCTGAGATATTGTCATCAAAACCTGCTCTCCCACTCCTATTGTCTCCACCAGGATGTCATCAAGCTGATGTGTTCTGACAACACAGTCAATGTTGTCTACGGACTCTGTGCAGGACTTTCTACTATGCTGGACTTGGTGTTTATTACCTTCTCCTATATGATTTTAAGGGCTGTACTGGGAATTGCTACCCCCAGACAGCAGTTCAAGGCCCTCAACACGTGCATCTCTCACATCTCTGGGATGTGTCTCCTATGATCCACGTCCTCATCGCTGATATTTTTCTGCTCGTCCCACCGCTGTGCTTATCTTCTATGTGCCCACGCTGAGTGCTGCCATGCTCCACCAGTTTGCCACCTGTTGAATCCCATCGTGTACTGTGTGAAGACCCACCAAATCCGAGAAAAGGTTGTGGGCAAACTTTGTCCAAAAGTAAGTTGATCAAAGGAATGAGAAAGGGAATGAATGTATAAORF Start: ATG at 17ORF Stop: TGA at 953SEQ ID NO:198312 aa MW at 35250.7 kDNOV66a,MSPLNDTRMEVLRFLLIGITGLEKSRTWISIPFLSVYLLSWMGNFTVLFFIKTEQSLHCG59224-01 Protein SequenceEPMYYLLSMLSTSDLGLSLSSLPITLSLFLFDVHETHAAPCFAQEFFIHLFTVSEASVLSVMAFDWYVAIHSPLRYSTTLTSPRAIKTGVLLTSKNVLLILPLPFLLQRLRYCHQNLLSHSYCLHQDVMKLMCSDNTVNVVYGLCAGLSTMLOLVFITFSYMILRAVLGTATPRQQFKALNTCISHICAVLTFYVPTLSAAMLHQFARDVSPMTHVLMADIFLLVPPLLNPIVYCVKTHQIREKVVGKLCPKVS


[0673] Further analysis of the NOV66a protein yielded the following properties shown in Table 66B.
349TABLE 66BProtein Sequence Properties NOV66aPSort0.6000 probability located in plasma membrane; 0.4000analysis:probability located in Golgi body; 0.3000 probability locatedin endoplasmic reticulum (membrane); 0.2007 probabilitylocated in mitochondrial inner membraneSignalPLikely cleavage site between residues 50 and 51analysis:


[0674] A search of the NOV66a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 66C.
350TABLE 66CGeneseq Results for NOV66aNOV66aIdentities/Protein/Residues/Similarities forGeneseqOrganism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAG72488Human OR-like1 . . . 312309/313 (98%)e−176polypeptide query1 . . . 313309/313 (98%)sequence, SEQ IDNO: 2169—Homosapiens, 319 aa.[WO200127158-A2,Apr. 19, 2001]AAG71557Human olfactory1 . . . 312309/313 (98%)e−176receptor poly-1 . . . 313309/313 (98%)peptide, SEQ IDNO: 1238—Homosapiens, 319 aa.[WO200127158-A2,Apr. 19, 2001]AAU24573Human olfactory1 . . . 310186/311 (59%)e−109receptor1 . . . 311246/311 (78%)AOLFR63—Homosapiens, 313 aa.[WO200168805-A2,Sep. 20, 2001]AAG71558Human olfactory1 . . . 310185/311 (59%)e−108receptor Homo1 . . . 311245/311 (78%)sapiens, 313 aa.[WO200127158-A2,Apr. 19, 2001]AAU24682Human olfactory1 . . . 307188/308 (61%)e−106receptor1 . . . 306237/308 (76%)AOLFR181—Homosapiens, 312 aa.[WO200168805-A2,Sep. 20, 2001]


[0675] In a BLAST search of public sequence databases, the NOV66a protein was found to have homology to the proteins shown in the BLASTP data in Table 66D.
351TABLE 66DPublic BLASTP Results for NOV66aNOV64aIdentities/ProteinResidues/Similarities forAccessionProteinMatchthe MatchedExpectNumberOrganism/LengthResiduesPortionValueAAL351091PROSTATE-14 . . . 304141/293 (48%)2e−77SPECIFIC G11 . . . 303199/293 (67%)PROTEIN-COUPLEDRECEPTORRA1C—Musmusculus(Mouse), 320 aa.O88628Olfactory14 . . . 304141/293 (48%)2e−77receptor 51E211 . . . 303200/293 (68%)(G-proteincoupled receptorRA1c)—Rattusnorvegicus(Rat), 320 aa.CAC38935SEQUENCE 9 5 . . . 304145/302 (48%)2e−77FROM PATENT 6 . . . 306206/302 (68%)WO0131014—Homo sapiens(Human), 318 aa.CAC37756SEQUENCE 1 5 . . . 304145/302 (48%)3e−77FROM PATENT 5 . . . 305206/302 (68%)WO0125434—Homo sapiens(Human), 317 aa.Q9H255Olfactory receptor14 . . . 304139/293 (47%)2e−7651E2 (Prostate11 . . . 303198/293 (67%)specific G-proteincoupled receptor)(HPRAJ)—Homo sapiens(Human), 320 aa.


[0676] PFam analysis predicts that the NOV66a protein contains the domains shown in the Table 66E.
352TABLE 66EDomain Analysis of NOV66aIdentities/NOV64aSimilarities forExpectPfam DomainMatch Regionthe Matched RegionValue7tm_1: domain43 . . . 15130/111 (27%)6.3e−141 of 273/111 (66%)7tm_1: domain43 . . . 151 16/92 (17%)0.0521 of 2 52/92 (57%)



Example 67

[0677] The NOV67 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 67A.
353TABLE 67ANOV67 Sequence AnalysisSEQ ID NO:199994 bpNOV67a,CACAATGTCTGTCTTCAATAGTTCTCCCTTATACCCTCCCTTCCTCCTAACGGGCCTCCG59222-01 DNA SequenceTCAGGCCTTGAAAGCAGATATGACTTGATTTCCCTGCCCATCTTCTTGGTTTATGCCACCTCAATTGCCGGGAACATTAGCATCCTCTTCATTATCAGAACTGAGTCTTCCCTCCACCAACCGATGTATTACTTTCTGTCAATGCTGGCATTCACTGACCTGGGCCTATCTAACACTACCTTACCTACCATGTTCAGTGTCTTCTGGTTCCATGCCCGCGAGATCTCCTTCAATGCTTCTCTGGTCCAAATGTACTTCATTCATCTTTTCTCGATTATTGAGTCAGCTGTACTCCTGGCTATGGCCTTTGACTGCTTTATAGCAATCTGTGAACCCTTGCGCTATGCAGCCATCCTAACCAATGATGTAATCATTGGGATTGGGTTGGCAATTGCTGGAAGGGCCTTGGCTCTGGTCTTTCCAGCTTCTTTCCTCTTGAAGAGGCTTCAATATCATGATGTCAATATTCTGTCCTACCTCTTCTGCCTGCACCAGGACCTCATAAAGACGACTGTATCCAACTGTCGAGTCAGCAGCATCTATGGCCTCATGGTGGTCATCTGTTCCATGGGACTTGATTCAGTCCTTCTCCTCCTCTCCTATGTCCTCATCCTCCCCACACTGTTCAGTATAGCCTCCAAGGCAGAGAGAGTGAGAGCCCTCAATACTTGCATCTCCCACATCTGTGCTGTACTCACCTTCTATACACCAATGATTCGCCTATCTATGATCCATCGCTATCCACAGAATCCTTCCTCAATTGTCCATGTGCTGATGGCCAATGTCTACTTGCTGGTTCCACCTCTCATGAACCCCGTTGTCTACAGTGTTAAGACCAAGCAGATTCGTGACAGAATCTTCAATAAATTCAAGAAACATGAAGTGTAGATCACAGAGATTCTCAAACATAACTTTCCCTCCATTCCCCATATATTTORF Start: ATG at 5ORF Stop: TAG at 944SEQ ID NO:200313 aaMW at 35044.2 kDNOV67a,MSVFNSSALYPRFLLTGLSGLESRYDLISLPIFLVYATSIAGNISILFIIRTESSLHQCG59222-01 Protein SequencePMYYFLSMLAFTDLGLSNTTLPTMFSVFWFHAREISFNACLVQMYFIHVFSIIESAVLLAMAFDCFIAICEPLRYAAILTNDVIIGIGLAIAGRALALVFPASFLLKRLQYHDVNILSYLFCLHQDLIKTTVSNCRVSSIYGLMVVICSMGLDSVLLLLSYVLILGTVLSIASKAERVRALNTCISHICAVLTPYTPMTGLSMIHRYGQNASSIVHVLMANVYLLVPPLMNPVVYSVKTKQIRDRIFNKFKKHEV


[0678] Further analysis of the NOV67a protein yielded the following properties shown in Table 67B.
354TABLE 67BProtein Sequence Properties NOV67aPSort0.6000 probability located in plasma membrane; 0.4047analysis:probability located in mitochondrial inner membrane; 0.4000probability located in Golgi body; 0.3480 probability locatedin mitochondrial intermembrane spaceSignalPNo Known Signal Sequence Predictedanalysis:


[0679] A search of the NOV67a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 67C.
355TABLE 67CGeneseq Results for NOV67aNOV67aIdentities/Protein/Residues/Similarities forGeneseqOrganism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAG72605Human OR-like1 . . . 309295/310 (95%) e−163polypeptide query4 . . . 313298/310 (95%)sequence, SEQ IDNO: 2286—Homosapiens, 318 aa.[WO200127158-A2,Apr. 19, 2001]AAG71519Human olfactory1 . . . 309295/310 (95%) e−163receptor poly-4 . . . 313298/310 (95%)peptide, SEQ IDNO: 1200—Homosapiens, 318 aa.[WO200127158-A2,Apr. 19, 2001]AAU24683Human olfactory5 . . . 308178/304 (58%) e−102receptor9 . . . 312235/304 (76%)AOLFR182—Homosapiens, 314 aa.[WO200168805-A2,Sep. 20, 2001]AAG71715Human olfactory5 . . . 308178/304 (58%) e−102receptor poly-9 . . . 312235/304 (76%)peptide, SEQ IDNO: 1396—Homosapiens, 314 aa.[WO200127158-A2,Apr. 19, 2001]ABB44526Human GPCR4a5 . . . 308169/304 (55%)2e−96 polypeptide SEQ ID6 . . . 309227/304 (74%)NO 11—Homosapiens, 315 aa.[WO200174904-A2,Oct. 11, 2001]


[0680] In a BLAST search of public sequence databases, the NOV67a protein was found to have homology to the proteins shown in the BLASTP data in Table 67D.
356TABLE 67DPublic BLASTP Results for NOV67aNOV67aIdentities/ProteinResidues/Similarities forAccessionProtein/Matchthe MatchedExpectNumberOrganism/LengthResiduesPortionValueQ9H344Olfactory13 . . . 308154/296 (52%)2e−91receptor 51I212 . . . 307221/296 (74%)(HOR5′beta12)—Homo sapiens(Human), 312 aa.Q9H2C8ODORANT 2 . . . 308160/307 (52%)5e−89RECEPTOR10 . . . 316216/307 (70%)HOR3′BETA1—Homo sapiens(Human), 321 aa.Q9H343Olfactory 5 . . . 312156/309 (50%)9e−89receptor 51I1 5 . . . 313223/309 (71%)(HOR5′beta11)—Homo sapiens(Human), 314 aa.AAL35109PROSTATE-13 . . . 309148/297 (49%)2e−86SPECIFIC G11 . . . 307207/297 (68%)PROTEIN-COUPLEDRECEPTORRA1C—Musmusculus(Mouse), 320 aa.Q924X8OLFACTORY 2 . . . 304150/303 (49%)1e−85RECEPTOR 3 . . . 305221/303 (72%)S85—Musmusculus(Mouse), 314 aa.


[0681] PFam analysis predicts that the NOV67a protein contains the domains shown in the Table 67E.
357TABLE 67EDomain Analysis of NOV67aIdentities/NOV67aSimilarities forExpectPfam DomainMatch Regionthe Matched RegionValue7tm_1: domain42 . . . 13824/99 (24%)7.8e−141 of 167/99 (68%)



Example 68

[0682] The NOV68 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 68A.
358TABLE 68ANOV68 Sequence AnalysisSEQ ID NO:201981 bpNOV68a,GCAATGAGAAACCGCAGTGTTGTCCCTGAGTTTGTCCTCCTCGGGCTGTCAGCTGGCCCG59220-01 DNA SequenceCCCACACCCACACTCTGCTCTTTGTGCTGTTCGTGGTGATTTGCCTCCTGACTGTGATGGGAAACCTGCTGCTGCTGGTGGTGATTAATGCTGATTCTTGCCTCCACACACCCATGTACTTCTTCCTGGGACAATTGTCCTTCTTGGATCTCTGCCATTCCTCTGTCACTGCACCTAAGCTGTTGGAGAACCTCCTGTCTGAGAAGAAAACCATCTCAGTAGAGGGCTGCATGGCTCAGGTCTTCTTTGTGTTTGCCACTGGGGGCACTGAATCCTCCCTGCTTGCTGTGATGGCCTATGACCGCTATGTTGCCATCAGCTCTCCTTTGCTCTATGCCCAACTGATGAACAGACAGCTGTGTTCAGGGCTGGTGGGGGGCTCATGGGGCTTGGCTTTTCTGGATGCCCTCATCAATATCCTTGTAGCTCTCAATTTAGACTTCTGTGACGCTCAAAATATCCACCACTTCAGCTGTGAGCTGCCCTCTCTCTATCCTTTGTCTTGCTCTGATGTGTCAGCAAGTTTTACCACCCTGCTCTGCTCCAGCTTCCTGCATTTCTTTGGAAATTTTCTCATGATATTCTTGTCTTATATTTGCATTTTGTCCACCATCCTGAGGATCAGCTCCACTACAGGCACAAGCAAAGCCTTCTCCACCTGCTCCTCCCACCTCACTGCACTGATTTTCTTTTATCGCTCCGGATTACTCCGCTATCTCATGCCAAATTCAGGATCCATTCAAGAGCTGATCTTCTCCTTGCAGTACAGCGTGATCACTCCCATGCTGAATCTCCTCATTTACAGCCTGAAGAACAGGGAGGTGAAGGCAGCTGTGAGAAGAACATTGAGAAAATATTTCTAGTGTTTCAATAGACTTATGAAATCAGAATGATGAGGGAACTGGATAGAACTGCAACAAGCAORF Start: ATG at 4ORF Stop: TAG at 919SEQ ID NO:202305 aaMW at 33732.3 kDNOV68aMRNRSVVPEFVLLGLSAGPQTQTLLFVLFVVICLLTVMGNLLLLVVINADSCLHTPMYCG59220-01 Protein SequenceFFLGQLSFLDLCHSSVTAPKLLENLLSEKKTISVEGCMAQVFFVFATGGTESSLLAVMAYDRYVAISSPLLYGQVMNRQLCSGLVGGSWGLAFLDALINILVALNLDFCEAQNTGRFSCELPSLYPLSCSDVSASFTTLLCSSFLHFFGNFLMTFLSYICTLSTILRISSTTGRSKAFSTCSSHLTAVIFFYGSGLLRYLMPNSGSIQELIESLQYSVITPMLNLLTYSLKNREVKAAVRRTLRKYF


[0683] Further analysis of the NOV68a protein yielded the following properties shown in Table 68B.
359TABLE 68BProtein Sequence Properties NOV68aPSort0.6400 probability located in plasma membrane; 0.4600analysis:probability located in Golgi body; 0.3700 probability locatedin endoplasmic reticulum (membrane); 0.1000 probabilitylocated in endoplasmic reticulum (lumen)SignalPLikely cleavage site between residues 50 and 51analysis:


[0684] A search of the NOV68a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 68C.
360TABLE 68CGeneseq Results for NOV68aNOV68aIdentities/Protein/Residues/Similarities forGeneseqOrganism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAU24771Human olfactory 3 . . . 304212/302 (70%) e−120receptor 5 . . . 306251/302 (82%)AOLFR328—Homo sapiens,312 aa.[WO200168805-A2, Sep. 20,2001]AAG98585Mouse olfactory66 . . . 279144/214 (67%)1e−78 receptor 7— 1 . . . 214169/214 (78%)Mus musculusdomesticus,214 aa.[WO200146262-A2, Jun. 28, 2001]AAG72680Murine OR-like 3 . . . 305148/305 (48%)3e−74 polypeptide query20 . . . 324201/305 (65%)sequence, SEQID NO: 2362—Mus musculus,337 aa.[WO200127158-A2, Apr. 19,2001]AAG71546Human olfactory 3 . . . 301143/302 (47%)2e−73 receptor poly- 5 . . . 306201/302 (66%)peptide, SEQ IDNO: 1227—Homo sapiens,315 aa.[WO200127158-A2, Apr. 19,2001]AAG66701Human GPCR1 3 . . . 301143/302 (47%)2e−73 polypeptide— 5 . . . 306201/302 (66%)Homo sapiens,311 aa.[WO200160865-A2, Aug. 23,2001]


[0685] In a BLAST search of public sequence databases, the NOV68a protein was found to have homology to the proteins shown in the BLASTP data in Table 68D.
361TABLE 68DPublic BLASTP Results for NOV68aNOV68aIdentities/ProteinResidues/Similarities forAccessionProtein/Matchthe MatchedExpectNumberOrganism/LengthResiduesPortionValueQ9JM36OLFACTORY66 . . . 279 144/214 (67%)5e−78RECEPTOR—Mus1 . . . 214169/214 (78%)musculusdomesticus(western Europeanhouse mouse), 214aa (fragment).Q9QZ18OLFACTORY3 . . . 299142/299 (47%)2e−72RECEPTOR—Mus5 . . . 303193/299 (64%)musculus (Mouse),312 aa.Q9EPG6B1 OLFACTORY3 . . . 299140/299 (46%)2e−72RECEPTOR—Mus5 . . . 303196/299 (64%)musculus (Mouse),314 aa.P23266Olfactory receptor-3 . . . 305142/305 (46%)9e−72like protein F5—5 . . . 309196/305 (63%)Rattus norvegicus(Rat), 313 aa.Q9EQA3ODORANT3 . . . 305143/306 (46%)2e−71RECEPTOR K30—5 . . . 310202/306 (65%)Mus musculus(Mouse), 311 aa.


[0686] PFam analysis predicts that the NOV68a protein contains the domains shown in the Table 68E.
362TABLE 68EDomain Analysis of NOV68aIdentities/NOV68aSimilarities forExpectPfam DomainMatch Regionthe Matched RegionValue7tm_1: domain39 . . . 286 54/268 (20%)1.7e−291 of 1169/268 (63%)



Example 69

[0687] The NOV69 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 69A.
363TABLE 69ANOV69 Sequence AnalysisSEQ ID NO:203957 bpNOV69a,GTCCACAATGGCCAATCAGACTGTGGTGACTGAGTTCTTCCTCCAAGGCCTGACGGATCG59218-01 DNA SequenceACCAAAGAGCTTCAGGTGGCTGTTTTTCTGCTCCTGCTGCTTGCCTACCTTGTGACTGTCTCTGGGAACCTGATCATCATCAGCCTGACCTTGCTGGACACCCGCCTGCAGACATCTATGTACTTATTTCTCCAGAATCTGTCCTGCTTAGAAATTTGGTTCCAGACAGTCATCGTGCCCAAGATGCTGCTCAACATTGCCATGGGGACCAAGACCGTTAGCTTTGCTGGGTGCATTACCCAGGACTTTTTCTTTCCACATCTTCTGGGGGCCACAGAGTTCTTCCTCCTCACAGCCATGGCCTATGACCAGTATATTGCCATCTGCAAGCCCCTCCACTACCCCATGCTCATAAGTAGTAGAGTCTGCACACAGCTCATCCTCACCTGCTGGCTACTAGGTTTCTCCTTCATCATCATGCCTGTCATCCTGACCAGTCAGCTTCCATTCTGTGATACCCACATCAAGCATTTCTTCTGTGACTACACGCCTCTAATGGAGGTGGTCTGCAGTGGGCCAAAGGTGCTGGAGATGGTGGATTTTACCCTGGCCTTAGTAGCACTGTTTGGCACCTTGGTACTCATCACCCTGTCCTATGTCCAGATCATCCAGACAATTGTCACAATCCCCGCTGTCCAGGAGAGGAAGAAGGCTTTCTCTACCTGTTCCTCTCATGTCATTATGGTTACCATGTGTTATGACAGCTCCTTCTTTATGTATGTCAAGCCCTCTCCAGGAAACTGGGTTGATGTCAACAAGGGAGTCTCTCTAATCAATACAATTATTGCCCCACTGTTAAATCCCTTCATCTCTACTCTGAGGAACCAACAAGTTAAGCAGGTAATGAAAGACCTAGTCAGAAAAATGACTTTGTTCCAAAATAAATAAGCGCCCTAAAAORF Start: ATG at 8ORF Stop: TAA at 944SEQ ID NO:204312 aaMW at 35358.1 kDNOV69a,MANQTVVTEFFLQGLTDTKELQVAVFLLLLLAYLVTVSGNLIIISLTLLDTRLQTSMYCG59218-01 Protein SequenceLFLQNLSCLEIWFQTVIVPKMLLNIAMGTKTVSFAGCITQDFFFPHLLGATEFFLLTAMAYDQYIAICRPLHYPMLISSRVCTQLILTCWLLGFSFTIMPVTLTSQLPFCDTHIKHFFCDYTPLMEVVCSGPKVLEMVDFTLALVALFGTLVLITLSYVQIIQTIVRIPAVQERKKAFSTCSSHVIMVTMCYDSCFFMYVKPSPGKWVDVNKGVSLINTIIAPLLNPFICTLRNQQVKQVMKDLVRKNTLFQNK


[0688] Further analysis of the NOV69a protein yielded the following properties shown in Table 69B.
364TABLE 69BProtein Sequence Properties NOV69aPSort0.6000 probability located in plasma membrane; 0.4000analysis:probability located in Golgi body; 0.3000 probability locatedin endoplasmic reticulum (membrane); 0.0300 probabilitylocated in mitochondrial inner membraneSignalPLikely cleavage site between residues 40 and 41analysis:


[0689] A search of the NOV69a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 69C.
365TABLE 69CGeneseq Results for NOV69aNOV69aIdentities/Protein/Residues/Similarities forGeneseqOrganism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAG72538Human OR-like1 . . . 312284/317 (89%)e−157polypeptide query1 . . . 313293/317 (91%)sequence, SEQ IDNO: 2219—Homosapiens, 313 aa.[WO200127158-A2,Apr. 19, 2001]AAG72229Human olfactory1 . . . 312284/317 (89%)e−157receptor poly-1 . . . 313293/317 (91%)peptide, SEQ IDNO:1910—Homosapiens, 313 aa.[WO200127158-A2,Apr. 19, 2001]AAU24761Human olfactory1 . . . 306173/307 (56%)2e−96receptor1 . . . 306227/307 (73%)AOLFR112B—Homo sapiens,309 2001]AAU24765Human olfactory1 . . . 306166/307 (54%)2e−94receptor1 . . . 306227/307 (73%)AOLFR225B—Homo sapiens,309 aa.[WO200168805-A2,Sep. 20, 2001]AAG66353GPCR partial1 . . . 309160/311 (51%)4e−87protein sequence—1 . . . 310209/311 (66%)Unidentified,313 aa.[WO200155179-A2,Aug. 2, 2001]


[0690] In a BLAST search of public sequence databases, the NOV69a protein was found to have homology to the proteins shown in the BLASTP data in Table 69D.
366TABLE 69DPublic BLASTP Results for NOV69aNOV69aIdentities/ProteinResidues/Similarities forAccessionProtein/Matchthe MatchedExpectNumberOrganism/LengthResiduesPortionValueQ9Z1V0OLFACTORY 1 . . . 309160/311 (51%)2e−86RECEPTOR 1 . . . 310209/311 (66%)C6—Musmusculus(Mouse), 313 aa.CAC88326SEQUENCE 18 8 . . . 306142/301 (47%)4e−78FROM PATENT12 . . . 311200/301 (66%)WO0164879—Homo sapiens(Human), 331 aa.CAC88328SEQUENCE 22 8 . . . 306142/301 (47%)2e−77FROM PATENT12 . . . 311198/301 (65%)WO0164879—Homo sapiens(Human), 331 aa.CAC88327SEQUENCE 20 8 . . . 306141/301 (46%)8e−77FROM PATENT12 . . . 311198/301 (64%)WO0164879—Homo sapiens(Human), 331 aa.O70270OLFACTORY 3 . . . 308136/307 (44%)4e−76RECEPTOR-11 . . . 316208/307 (67%)LIKEPROTEIN—Rattusnorvegicus (Rat),327 aa.


[0691] PFam analysis predicts that the NOV69a protein contains the domains shown in the Table 69E.
367TABLE 69EDomain Analysis of NOV69aIdentities/NOV69aSimilarities forExpectPfam DomainMatch Regionthe Matched RegionValue7tm_1: domain39 . . . 244 47/214 (22%)1.9e−251 of 1147/214 (69%)



Example 70

[0692] The NOV70 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 70A.
368TABLE 70ANOV70 Sequence AnalysisSEQ ID NO:205962 bpNOV70a,CATCTTCCTATGTGTCATGTCTCCTCTTAATGACACAAAAATGGAAGTCCTTAGATTCCG59216-01 DNA SequenceCTCCTTATCGGGATCACTGGACTGCAGAAAAGTCGCACCTGGATATCCATTCCTTTCTTATCTGTGTACCTTCTTTCTTCGATCGGTAATTTTACCGTCCTCTTTTTTATCAAGACAGACCAAAGCCTCCATCAACCTATGTATTATTTGCTTTCCATGCTCTCCATCTCTGACCTAGGGCTGTCTCTGTCTTCCTTACCCATCACTTTGGGACTATTCCTATTTGATGTCCATGAAATTCATGCAGCTCCATGCTTTGCCCAGGAATTTTTTATCCATCTGTTTACAGTCAGTGAAGCCTCTGTACTGTCTGTAATGGCATTTGACTGGTATGTGGCAATCCACAGTCCTTTGAGATACAGCACTATCTTAACTAGTCCCAGAGCCATCAAAACAGGGGTTCTTCTGACTTCCAAGAATGTTCTTTTGATCCTTCCACTGCCCTTTCTCTTGCAAAGGCTGAGATATTGTCATCAAAACCTGCTCTCCCACTCCTATTGTCTCCACCAGGATGTCATGAAGCTGATGTGTTCTGACAACACAGTCAATGTTGTCTACGGACTCTGTGCAGGACTTTCTACTATGCTCCACTTGGTGTTTATTACCTTCTCCTATATTATGATTTTAAGGGCTGTACTGGGAATTGCTACCCCCAGACAGCAGTTCAAGCCCCTCAACACCTCCATCTCTCACATCTGTGCTCTCCTTATCTTCTATGTGCCCACGCTGAGTGCTCCCATGCTCCACCAGTTTCCCAGGGATGTGTCTCCTATGATCCACGTCCTCATGGCTGATATTTTTCTGCTGGTGCCACCCCTGTTGAATCCCATCGTGTACTGTGTGAAGACCCACCAAATCCGAGAAAAGGTTGTGGGGAAACTTTGTCCAAAAGTAAGTTGATCAAORF Start: ATG at 17ORF Stop: TGA at 956SEQ ID NO:206313 aaMW at 35363.9 kDNOV70a,MSPLNDTKMEVLRFLLIGITGLEKSRTWISIPFLSVYLLSWMGNFTVLFFIKTEQSLHCG59216-01 Protein SequenceEPMYYLLSMLSISDLGLSLSSLPITLGLFLFDVHEIHAAPCFAQEFFIHLFTVSEASVLSVMAFDWYVAIHSPLRYSTILTSPRAIKTGVLLTSKNVLLILPLPFLLQRLRYCHQNLLSHSYCLEQDVMKLMCSDNTVNVVYGLCAGLSTMLDLVFTTFSYTMILRAVLGIATPRQQFKALNTCISHICAVLIFYVPTLSAAMLHQFARDVSPMTHVLMADIFLLVPPLLNPIVYCVKTHQIREKVVCKLCPKVS


[0693] Further analysis of the NOV70a protein yielded the following properties shown in Table 70B.
369TABLE 70BProtein Sequence Properties NOV70aPSort0.6000 probability located in plasma membrane; 0.4000analysis:probability located in Golgi body; 0.3000 probability locatedin endoplasmic reticulum (membrane); 0.2007 probabilitylocated in mitochondrial inner membraneSignalPLikely cleavage site between residues 50 and 51analysis:


[0694] A search of the NOV70a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 70C.
370TABLE 70CGeneseq Results for NOV70aNOV70aIdentities/Protein/Residues/Similarities forGeneseqOrganism/LengthMatchthe MatchedExpectIdentifier[Patent #, Date]ResiduesRegionValueAAG72488Human OR-like1 . . . 313310/313 (99%)e−178polypeptide query1 . . . 313310/313 (99%)sequence, SEQ IDNO: 2169—Homosapiens, 319 aa.[WO200127158-A2,Apr. 19, 2001]AAG71557Human olfactory1 . . . 313310/313 (99%)e−178receptor poly-1 . . . 313310/313 (99%)peptide, SEQ IDNO: 1238—Homosapiens, 319 aa.[WO200127158-A2,Apr. 19, 2001]AAU24573Human olfactory1 . . . 311186/311 (59%)e−110receptor1 . . . 311246/311 (78%)AOLFR63—Homosapiens, 313 aa.[WO200168805-A2,Sep. 20, 2001]AAG71558Human olfactory1 . . . 311185/311 (59%)e−109receptor poly-1 . . . 311245/311 (78%)peptide, SEQ IDNO: 1239—Homosapiens, 313 aa.[WO200127158-A2,Apr. 19, 2001]AAU24682Human olfactory1 . . . 308188/308 (61%)e−107receptor1 . . . 306238/308 (77%)AOLFR181 —Homo sapiens,312 aa.[WO200168805-A2,Sep. 20, 2001]


[0695] In a BLAST search of public sequence databases, the NOV70a protein was found to have homology to the proteins shown in the BLASTP data in Table 70D.
371TABLE 70DPublic BLASTP Results for NOV70aNOV70aIdentities/ProteinResidues/Similarities forAccessionProtein/Matchthe MatchedExpectNumberOrganism/LengthResiduesPortionValueCAC38935SEQUENCE 9 5 . . . 305145/302 (48%)5e−79FROM PATENT 6 . . . 306207/302 (68%)WO0131014—Homo sapiens318 aa.AAL35109PROSTATE-14 . . . 305141/293 (48%)7e−79SPECIFIC G11 . . . 303199/293 (67%)PROTEIN-COUPLEDRECEPTORRA1C—Musmusculus(Mouse), 320 aa.CAC37756SEQUENCE 1 5 . . . 305145/302 (48%)7e−79FROM PATENT 5 . . . 305207/302 (68%)WO0125434—Homo sapiens(Human), 317 aa.O88628Olfactory receptor14 . . . 305141/293 (48%)7e−7951E2 (G-protein11 . . . 303200/293 (68%)coupled receptorRA1c)—Rattusnorvegicus(Rat), 320 aa.Q9H255Olfactory receptor14 . . . 305139/293 (47%)7e−7851E2 (Prostate11 . . . 303198/293 (67%)specific G-proteincoupled receptor)(HPRAJ)—Homosapiens(Human), 320 aa.


[0696] PFam analysis predicts that the NOV70a protein contains the domains shown in the Table 70E.
372TABLE 70EDomain Analysis of NOV70aIdentities/NOV70aSimilarities forExpectPfam DomainMatch Regionthe Matched RegionValue7tm_1: domain 43 . . . 15130/111 (27%)6.3e−141 of 273/111 (66%)YCF9: domain208 . . . 262 10/59 (17%)7.5  1 of 1 31/59 (53%)7tm_1: domain212 . . . 293 18/93 (19%)0.000342 of 2 55/93 (59%)



Example 71

[0697] The NOV71 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 71A.
373TABLE 71ANOV71 Sequence AnalysisSEQ ID NO:207995 bpNOV71a,GCACAATGTCTGTCTTCAATAGTTCTGCCTTATACCCTCGCTTCCTCCTAACGGGCCTCG59214-01 DNA SequenceCTCAGGCCTTGAAAGCAGATATGACTTGATTTCCCTGCCCATCTTCTTGGTTTATGCCACCTCAATTGCCGGGAACATTAGCATCCTCTTCATTATCAGAACTGAGTCTTCCCTCCACCAACCGATGTATTACTTTCTGTCAATGCTGGCATTCACTGACCTGGGCCTATCTAACACTACCTTACCTACCATGTTCAGTGTCTTCTGGTTCCATGCCCGGGAGATCTCCTTCAATGCTTGTCTGGTCCAAATGTACTTCATTCATGTTTTCTCGATTATTGAGTCAGCTGTACTCCTGGCTATCGCCTTTGACTGCTTTATAGCAATCTGTGAACCCTTGCGCTATGCAGCCATCCTAACCAATGATGTAATCATTGGGATTGCGTTGGCAATTGCTGGAAGGGCCTTGGCTCTGGTCTTTCCAGCTTCTTTCCTCTTGAAGAGGCTTCAATATCATGATGTCAATATTCTGTCCTACCTCTTCTGCCTGCACCAGGACCTCATAAAGACGACTGTATCCAACTGTCGAGTCAGCAGCATCTATGGCCTCATGGTGGTCATCTGTTCCATGGGACTTGATTCAGTGCTTCTCCTCCTCTCCTATGTCCTCATCCTGGGCACAGTGTTGAGTATAGCCTCCAAGGCAGAGAGAGTGAGAGCCCTCAATACTTGCATCTCCCACATCTGTGCTGTACTTCCTCAATTGTCCATGTGCTGATGGCCAATGTCTACTTGCTGGTTCCACCTCTCATGACACCTTCTATACACCAATGATTGGGCTATCTATGATCCATCGCTATGGACASAATGCTACCCCGTTGTCTACAGTGTTAAGACCAAGCAGATTCGTGACAGAATCTTCAATAAATTCAAGAAACATGAAGTGTAGATGACAGAGATTCTGAAACATAACTTTCCCTCCATTCCCCATATATTTORF Start: ATG at 6ORF Stop: TAG at 945SEQ ID NO:208313 aaMW at 35044.2 kDNOV71a,MSVFNSSALYPRFLLTGLSGLESRYDLISLPTELVYATSIAGNTSILFTTRTESSLHQCG59214-01 Protein SequencePMYYFLSMLAFTDLGLSNTTLPTMFSVFWFHAREISFNACLVQMYFIHVFSIIESAVLLAMAFDCFIAICEPLRYAATLTNDVIISTGLAIAGRALALVFPASFLLKRLQYHDVNILSYLFCLHQDLTKTTVSNCRVSSIYGLMVVICSMGLDSVLLLLSYVLILCTVLSTASKAERVRALNTCISHICAVLTFYTPMIGLSMTHRYGQNASSTVHVLMANVYLLVPPLMNPVVYSVKTKQIRDRIFNKFKKHEV


[0698] Further analysis of the NOV71a protein yielded the following properties shown in Table 71B.
374TABLE 71BProtein Sequence Properties NOV71aPSort0.6000 probability located in plasma membrane; 0.4047analysis:probability located in mitochondrial inner membrane;0.4000 probability located in Golgi body; 0.3480probability located in mitochondrial intermembrane spaceSignalPNo Known Signal Sequence Predictedanalysis:


[0699] A search of the NOV71a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 71C.
375TABLE 71CGeneseq Results for NOV71aIdentities/NOV71aSimilarities forGeneseqProtein/Organism/LengthResidues/the MatchedExpectIdentifier[Patent #, Date]Match ResiduesRegionValueAAG72605Human OR-like polypeptide1 . . . 309295/310 (95%) e−163query sequence, SEQ ID NO:4 . . . 313298/310 (95%)2286 - Homo sapiens, 318 aa.[WO200127158-A2, 19 APR2001]AAG71519Human olfactory receptor1 . . . 309295/310 (95%) e−163polypeptide, SEQ ID NO: 1200 -4 . . . 313298/310 (95%)Homo sapiens, 318 aa.[WO200127158-A2, 19 APR2001]AAU24683Human olfactory receptor5 . . . 308178/304 (58%) e−102aa. [WO200168805-A2, 20 SEP9 . . . 312235/304 (76%)2001]AAG71715Human olfactory receptor5 . . . 308178/304 (58%) e−102polypeptide, SEQ ID NO: 1396 -9 . . . 312235/304 (76%)Homo sapiens, 314 aa.[WO200127158-A2, 19 APR2001]ABB44526Human GPCR4a polypeptide5 . . . 308169/304 (55%)2e−96SEQ ID NO 11 - Homo sapiens,6 . . . 309227/304 (74%)315 aa. [WO200174904-A2,11 OCT 2001]


[0700] In a BLAST search of public sequence databases, the NOV71a protein was found to have homology to the proteins shown in the BLASTP data in Table 71D.
376TABLE 71DPublic BLASTP Results for NOV71aNOV71aIdentities/ProteinResidues/Similarities forAccessionMatchthe MatchedExpectNumberProtein/Organism/LengthResiduesPortionValueQ9H344Olfactory receptor 51I213 . . . 308154/296 (52%)2e−91(HOR5′beta12) - Homo sapiens12 . . . 307221/296 (74%)(Human), 312 aa.Q9H2C8ODORANT RECEPTOR 2 . . . 308160/307 (52%)5e−89HOR3′BETA1 - Homo sapiens10 . . . 316216/307 (70%)Human), 321 aa.Q9H343Olfactory receptor 51I1 5 . . . 312156/309 (50%)9e−89(HOR5′beta11) - Homo sapiens 5 . . . 313223/309 (71%)(Human), 314 aa.AAL35109PROSTATE-SPECIFIC G13 . . . 309148/297 (49%)2e−86PROTEIN-COUPLED11 . . . 307207/297 (68%)RECEPTOR RA1C - Musmusculus (Mouse), 320 aa.Q924X8OLFACTORY RECEPTOR S85 - 2 . . . 304150/303 (49%)1e−85Mus musculus (Mouse), 314 aa. 3 . . . 305221/303 (72%)


[0701] PFam analysis predicts that the NOV71a protein contains the domains shown in the Table 71E.
377TABLE 71EDomain Analysis of NOV71aIdentities/SimilaritiesNOV71afor thePfam DomainMatch RegionMatched RegionExpect Value7tm_1:42 . . . 13824/99 (24%)7.8e−14domain 1 of 167/99 (68%)


[0702] The NOV72 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 72A.
378TABLE 72ANOV72 Sequence AnalysisSEQ ID NO:2091004 bpNOV72a,CTTCTCATCTTTTCCCTCAAATACTGGGATGTCCATTCTCAATACCTCTGAAATGGAACG59211-01 DNA SequenceATCTCTATTTTCTACTTGGTTGGGATCCCAGGTTTGGAGCATGCCAATATTTGGATCTCTATCCCCATATGTCTCATGTACACTGTTGCTATCCTAGGGAATTGTACCATTCTGTTTTTCATAAAAACACAGCCTTCTTTGCATGAGCCCATGTACTATTTTCTCTCCATGTTGGCTCTCTCTGACCTGGGACTATCCCTCTCCTCTCTCCCTACCATGTTAACGATTTTCCTGTTCAATGCTCCAGGAATTTCCCCTGATGCCTGTATTGCTCAAGAGTTTTTCATCCATGGATTCTCAGCTATGGAGTCATCTGTACTTCTTATAATGTCCTTTGATCGCTTTATTGCCATCTGCAACCCCCTGAGATACACTTCCATCCTCACCAGTCCCAGAGTCATTCAAATTGGGCTTGCTTTTTCTCTCAAAAATCTTTTGTTCATCCTCCCATTTCCTTTCACTCTAAAACATCTAAAATATTGTAAGAAGAACCTCCTGTCCCAATCCTACTGCCTCCATCAAGATGTCATGAAACTGGCCTGCACTGACAACAAGGTCAACATCATCTATGGCTTATTTGTGGCTCTCACAGGCATCCTAGACTTGACATTTATTTTCATGTCCTACATCTTGATACTGAAAGCAGTGTTGAGCATAGCATCAAGAAAGAAAAGGCTCAAGGTCCTCAATACATGTGTTTCCCACATCTGTGCTGTGCTCATCTTCTATGTGCCCATTATCTCCCTAGCTGTCATCTACCGGTTTGCCAAACACAGTTTCCCAATCACTAGGATCCTCATAGCTGATGCTTTTCTGCTGGTGCCTCCATTGATGAACCCCATTGTATACTGTGTGAAGAGCCAGCAGATAAGAAATCTTCTCTTAGAAAAACTGTGCCAGAAGCAAAGCTGAAGCGGATGCTTAACCACATGATGCTTAACCCAAAORF Start: ATG at 29ORF Stop: TGA at 968SEQ ID NO:210313 aaMW at 35313.1 kDNOV72a,MSILNTSEMEISIFYLVGIPGLEHANIWISIPICLMYTVAILGNCTILFFIKTEPSLHCG59211-01 Protein SequenceEPMYYFLSMLALSDLGLSLSSLPTMLRIFLFNAPGISPDACIAQEFFIHGFSAMESSVLLIMSFDRFIAICNPLRYTSILTSARVIQIGLAFSLKNVLLILPFPFTLKHLKYCKKNLLSQSYCLHQDVMKLACTDNKVNIIYGLFVALTGILDLTFTEMSYMLTLKAVLSIASRKKRLKVLNTCVSHICAVLTFYVPIISLAVIYRFAKHSFPTTRTLIADAFLLVPPLMNPIVYCVKSQQIRNLVLEKLCQKQS


[0703] Further analysis of the NOV72a protein yielded the following properties shown in Table 72B.
379TABLE 72BProtein Sequence Properties NOV72aPSort0.6000 probability located in plasma membrane; 0.4000analysis:probability located in Golgi body; 0.3000 probability locatedin endoplasmic reticulum (membrane); 0.0300 probabilitylocated in mitochondrial inner membraneSignalPLikely cleavage site between residues 44 and 45analysis:


[0704] A search of the NOV72a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 72C.
380TABLE 72CGeneseq Results for NOV72aIdentities/NOV72aSimilarities forGeneseqProtein/Organism/LengthResidues/the MatchedExpectIdentifier[Patent #, Date]Match ResiduesRegionValueAAG71564Human olfactory receptor1 . . . 313312/313 (99%)e−177polypeptide, SEQ ID NO: 1245 -5 . . . 317312/313 (99%)Homo sapiens, 322 aa.[WO200127158-A2, 19 APR 2001]AAU24573Human olfactory receptor1 . . . 312225/312 (72%)e−131AOLFR63 - Homo sapiens, 313 aa.1 . . . 312272/312 (87%)[WO200168805-A2, 20 SEP 2001]AAG71721Human olfactory receptor1 . . . 311236/312 (75%)e−131polypeptide, SEQ ID NO: 1402 -1 . . . 311267/312 (84%)Homo sapiens, 316 aa.[WO200127158-A2, 19 APR 2001]AAU24682Human olfactory receptor1 . . . 308224/308 (72%)e−131AOLFR181 - Homo sapiens, 3121 . . . 306265/308 (85%)aa. [WO200168805-A2, 20 SEP 2001]AAG71701Human olfactory receptor1 . . . 308224/308 (72%)e−131polypeptide, SEQ ID NO: 1382 -1 . . . 306265/308 (85%)Homo sapiens, 312 aa.[WO200127158-A2, 19 APR 2001]


[0705] In a BLAST search of public sequence databases, the NOV72a protein was found to have homology to the proteins shown in the BLASTP data in Table 72D.
381TABLE 72DPublic BLASTP Results for NOV72aNOV72aIdentities/ProteinResidues/Similarities forAccessionMatchthe MatchedExpectNumberProtein/Organism/LengthResiduesPortionValueQ9H344Olfactory receptor 51I212 . . . 304 152/294 (51%)6e−90(HOR5′beta12) - Homo sapiens10 . . . 303 219/294 (73%)(Human), 312 aa.Q9EQQ7MOR 3′BETA4 - Mus musculus1 . . . 309159/310 (51%)9e−89(Mouse), 319 aa.1 . . . 310219/310 (70%)Q9H343Olfactory receptor 51I14 . . . 313154/311 (49%)9e−89(HOR5′beta11) - Homo sapiens4 . . . 314226/311 (72%)(Human), 314 aa.CAC38935SEQUENCE 9 FROM PATENT5 . . . 305153/302 (50%)2e−87WO0131014 - Homo sapiens6 . . . 306217/302 (71%)(Human), 318 aa.CAC37756SEQUENCE 1 FROM PATENT5 . . . 305153/302 (50%)3e−87WO0125434 - Homo sapiens5 . . . 305217/302 (71%)(Human), 317 aa.


[0706] PFam analysis predicts that the NOV72a protein contains the domains shown in the Table 72E.
382TABLE 72EDomain Analysis of NOV72aIdentities/SimilaritiesNOV72afor thePfam DomainMatch RegionMatched RegionExpect ValueDUF40: domain109 . . . 13410/26(38%)0.381 of 120/26(77%)7tm_1: 43 . . . 14427/107(25%)1.6e−15domain 1 of 271/107(66%)7tm_1:212 . . . 29316/93(17%)4.7domain 2 of 256/93(60%)Sina: domain 1 of 1300 . . . 3117/12(58%)110/12(83%)



Example 73

[0707] The NOV73 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 73A.
383TABLE 73ANOV73 Sequence AnalysisSEQ ID NO:2111581 bpNOV73a,CTGGTGGGTTGGCGGCTAACGGCCGGAGACAAGAGCGGCCGCCACCATCTCCTCCAATCG59276-01 DNA SequenceGGAAGGGAGACAGGGGCGGGCTTAATGACGGAAGGAGCATGGCGTGGAGACACCTGAAAAAGCGGGCCCAGGATGCTCTCATCATCCTGGGGGCAGGAGGACTTCTCTTCGCCTCCTACCTGATGGCCACGGGAGATGAGCGTTTCTATGCTGAACACCTGATGCCGACTCTGCAGGGGCTGCTGGACCCGGAGTCAGCCCACAGACTGGCTGTTCGCTTCACCTCCCTGGGGCTCCTTCCACGGGCCAGATTTCAAGACTCTGACATGCTGGAAGTGAGAGTTCTGGGCCATAAATTCCGAAATCCAGTAGGAATTGCTGCAGCATTTGACAAGCATGGGGAAGCCGTGGACGGACTTTATAAGATGGGCTTTGGTTTTGTTGAGATAGGAAGTGTGACTCCAAAACCTCAGGAAGGAAACCCTAGACCCAGAGTCTTCCGCCTCCCTGAGGACCAAGCTGTCATTAACAGGTATGGATTTAACAGTCACGGGCTTTCAGTGGTGGAACACAGGTTACGGGCCAGACAGCAGAAGCAGGCCAAGCTCACAGAAGATGGACTGCCTCTGGGGGTCAACTTGGGGAAGAACAAGACCTCAGTGGACGCCGCGGAGGACTACGCAGAAGGGGTGCGCGTACTGGGCCCCCTGGCCGACTACCTGCTGGTGAATGTGTCCAGCCCCAACACTGCCGGGCTGCGGAGCCTTCAGGGAAAGGCCGAGCTGCGCCGCCTGCTGACCAAGGTGCTCCAGGAGAGGGATGGCTTGCGGAGAGTGCACAGGCCGGCAGTCCTGGTGAAGATCGCTCCTGACCTCACCAGCCAGGATAAGGAGGACATTGCCAGTGTGGTCAAAGAGTTGGGCATCGATGGGCTGATTGTTACGAACACCACCGTGAGTCGCCCTGCGGGCCTCCAGGGTGCCCTGCGCTCTGAAACAGGAGGGCTGAGTGGGAAGCCCCTCCGGGATTTATCAACTCAAACCATTCGGGAGATGTATGCACTCACCCAAGGCAAGGTTTCCCGTCGACTTCCCATAATTGGGGTTGGTGGTGTGAGCAGCGGGCAGGACGCGCTGGAGAAGATCCGGGCAGGGGCCTCCCTGGTGCAGCTGTACACGGCCCTCACCTTCTGGGGGCCACCCGTTGTGGGCAAAGTCAAGCGGGAACTGGAGGCCCTTCTGAAGGAGCAGGGCTTTGGCGGAGTCACAGATGCCATTGGAGCAGATCATCGGAGCATGAGGAAACGGGCAGAGAAGCGGCTGATTGTCCAGTCCCCCTGCGTGGAGGCTGCTTGGCTGGGCTCCAGCCCAGCGGTGGTGGGTCAGTTGGCACCTGGTGGTCTGCTGGTGGTCAGTTTGGGAATTTCCAGGTACGATTGTTTTCAGGCACTGTTCTTTGACTTGGTTGCAGAAAAACAGATTTTGCAACACTTTCCAAGGACACAGTGTTACCACTCCCTCACCCTGCCATGGCCTCTTGGTTCTGCTTTTAACTTCTGAGCCTCAGGGAGTCCATCTTGTCTGORF Start: ATG at 97ORF Stop: TGA at 1555SEQ ID NO:212486 aaMW at 52982.6 kDNOV73a,MAWRHLKKRAQDAVIILGGGGLLFASYLMATGDERFYAEHLMPTLQGLLDPESAHRLACG59276-01 Protein SequenceVRFTSLGLLPRARFQDSDMLEVRVLGHKFRNPVGIAAGFDKHGEAVDGLYKMGFGFVEIGSVTPKPQEGNPRPRVFRLPEDQAVINRYGFNSHGLSVVEHRLRARQQKQAKLTEDGLPLGVNLGKNKTSVDAAEDYAEGVRVLGPLADYLVVNVSSPNTAGLRSLQGKAELRRLLTKVLQERDCLRRVHRPAVLVKIAPDLTSQDKEDTASVVKELGZDCLIVTNTTVSRPAGLQGALRSETGGLSGKPLRDLSTQTIREMYALTQGKVSRRVPIIGVGGVSSGQDALEKIRAGASLVQLYTALTFWGPPVVGKVKRELEALLKEQGFGGVTDAIGADHRRMRKRAEKRLIVQSPCVEAAWLGSSPAVVGQLGPGGLLVVSLGISRYDCFQALFFDLVAEKQILQHFPRTQCYHSLTLPWPLGSAFNF


[0708] Further analysis of the NOV73a protein yielded the following properties shown in Table 73B.
384TABLE 73BProtein Sequence Properties NOV73aPsort0.8110 probability located in plasma membrane; 0.6400analysis:probability located in endoplasmic reticulum (membrane);0.3700 probability located in Golgi body; 0.1839 probabilitylocated in microbody (peroxisome)SignalPNo Known Signal Sequence Predictedanalysis:


[0709] A search of the NOV73a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 73C.
385TABLE 73CGeneseq Results for NOV73aIdentities/NOV73aSimilarities forGeneseqProtein/Organism/LengthResidues/the MatchedExpectIdentifier[Patent #, Date]Match ResiduesRegionValueAAB70780Tobacco dihydro-orotase protein -36 . . . 398199/383 (51%) e−101Nicotiana tabacum, 458 aa.81 . . . 458257/383 (66%)[WO200118190-A2, 15 MAR 2001]AAG01301Human secreted protein, SEQ ID 1 . . . 144143/144 (99%)3e−79NO: 5382 - Homo sapiens, 144 aa. 1 . . . 144144/144 (99%)[EP1033401-A2, 6 SEP 2000]AAG91420C glutamicum protein fragment SEQ76 . . . 396131/328 (39%)6e−60ID NO: 5174 - Corynebacterium60 . . . 366190/328 (56%)glutamicum, 371 aa. [EP1108790-A2, 20 JUN 2001]AAB46597C. glutamicum dihydroorotate76 . . . 396131/328 (39%)6e−60dehydrogenase protein -10 . . . 316190/328 (56%)Corynebacterium glutamicum, 321aa. [DE19929364-A1, 28 DEC 2000]AAB80123Corynebacterium glutamicum MP76 . . . 396131/328 (39%)1e−59protein sequence SEQ ID NO:980 -23 . . . 329190/328 (56%)Corynebacterium glutamicum, 334aa. [WO200100843-A2, 4 JAN2001]


[0710] In a BLAST search of public sequence databases, the NOV73a protein was found to have homology to the proteins shown in the BLASTP data in Table 73D.
386TABLE 73DPublic BLASTP Results for NOV73aNOV73aIdentities/ProteinResidues/Similarities forAccessionMatchthe MatchedExpectNumberProtein/Organism/LengthResiduesPortionValueQ02127Dihydroorotate dehydrogenase,1 . . . 399392/399 (98%)0.0mitochondrial precursor (EC 1.3.3.1)2 . . . 396394/399 (98%)(Dihydroorotate oxidase)(DHOdehase) - Homo sapiens(Human), 396 aa (fragment).PC1219dihydroorotate oxidase (EC 1.3.3.1)1 . . . 399388/399 (97%)0.0precursor - human, 397 aa.3 . . . 397393/399 (98%)Q63707Dihydroorotate dehydrogenase,1 . . . 399350/399 (87%)0.0mitochondrial precursor (EC 1.3.3.1)1 . . . 395369/399 (91%)(Dihydroorotate oxidase)(DHOdehase) - Rattus norvegicus(Rat), 395 aa.O35435Dihydroorotate dehydrogenase,1 . . . 399346/399 (86%)0.0mitochondrial precursor (EC 1.3.3.1)1 . . . 395366/399 (91%)(Dihydroorotate oxidase)(DHOdehase) - Mus musculus(Mouse), 395 aa.Q9FZM9DIHYDROOROTATE29 . . . 398 206/394 (52%)e−101DEHYDROGENASE - Oryza sativa79 . . . 468 261/394 (65%)(Rice), 468 aa.


[0711] PFam analysis predicts that the NOV73a protein contains the domains shown in the Table 73E.
387TABLE 73EDomain Analysis of NOV73aIdentities/SimilaritiesNOV73afor thePfam DomainMatch RegionMatched RegionExpect ValueDHOdehase:77 . . . 381183/331 (55%)1.9e−169domain 1 of 1282/331 (85%)



Example 74

[0712] The NOV74 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 74A.
388TABLE 74ANOV74 Sequence AnalysisSEQ ID NO:2131875 bpNOV74a,ATGGCCGCAGCCTCGCCTCTGCGCGACTGCCAGGCCTGGAAGGATGCGAGGCTCCCGCCG59268-01 DNA SequenceTCTCCACCACAAGCAACGAAGCCTGCAAGCTGTTCGATGCCACGCTGACCCAGTATGTAAAATGGACCAATGACAAGACTCTCGCTGGCATCGAGGGCTGCCTGTCAAAGCTCAAAGCAGCAGATCCAACCTTTGTGATGGGCCACGCCATGGCTACTGGCCTTGTGCTGATTGGCACTGGAAGCTCCGTGAAGCTGGACAAAGAGCTGGACCTGGCTGTGAAGACAATGGTGGAGATTTCAAGAACCCAGCCGCTGACAAGGCGGGAGCAGCTGCACGTGTCTGCAGTAGAGACATTTGCCAATGGGAACTTTCCGAAAGCCTGTGAACTATGGGAACAGATTCTCCAGGACCACCCGACAGACATGTTGGCCCTGAAATTTTCCCATGATGCTTATTTTTACCTGGGCTATCAGGAACAGATGAGAGATTCTGTTGCTCGAATTTACCCCTTCTGCACACCTGACATCCCCCTAAGCAGCTATGTGAAAGGCATCTACTCTTTTGGCTTGATGGAAACCAACTTCTACGACCAGGCAGAAAAACTCGCCAAAGAGGCACCAACTCTTTGTCTTCAACACCAGCACCCCACAGACAACTACTGGGCAGGAAAAGCAGGCTGTGATGGGGCCAGGAGTGGTAACACATGGGCTCTGTGTCTGCAGCCCCAGGCTGACGCATGGTCCCTGCACACCGTCGCTCACATCCACGAGATGAAAGCAGAGATCAAGGATGGGTTGGAATTCATGCAGCACTCAGAGACCTTCTGGAAGGACTCTGATATGTTGGCTTGTCATAACTATTGGCACTGGGCTTTATATCTGATTGAGAAGGGTTTAATAACGACAACTTTATTCTTCCAGGGCGAATATGAGGCCGCGCTGACCATCTACGATACCCACATCCTTCCCAGCCTGCAGGCCAACGATGCAATGCTGGACGTGGTGGACAGCTGCTCCATGCTCTACCGCCTGCAGATGGAAGGAGTGTCTGTGGGCCAGCGGTGGCAGGATGTCCTGCCTGTGGCCCGGAAGCACAGCCGAGACCACATCCTGCTGTTCAATGACGCACACTTCCTGATGGCATCCCTGGGTGCACACGACCCCCAGACCACACAGGAGCTGCTGACCACCCTGCGGGACGCCAGCGAGTATGCAGAGGGGCCTTCTCGGGGTGGGGGTCCTCACCCTGCCGAGAGGTGCCAGGCCTTTGCCTGTATTATCAGCAATCCTGACGGTTCTGTTAGATTGGCACTGTTATGCCTGCTTACAGATGAGCAAACTGAGGCTGGAAGATCCCCAGGGGAGAACTGCCAGCACCTCCTGGCCCGAGACGTGGGGCTGCCCCTGTGCCAGGCCCTGGTGGAGGCTGAGGACGGGAACCCTGACCGCGTCCTGGAGCTGCTCCTGCCCATCCGCTACCGGATCGTCCAGCTCGGTGGGAGCAATGCCCAGAGAGACGTCTTCAACCAGCTGCTGATTCACGCGGCCTTAAACTGCACCTCCAGCGTCCATAAGAACGTAGCCCGGAGCCTTCTGATGGAGCGTGATGCCTTGAAGCCCAACTCGCCCCTCACCGAGCGGCTCATCCGCAAGGCAGCTACCGTCCACCTCATGCAGAAGCCTTCTACCCGCCAACCCCCACTGCAGGCTGCTCTCTCCATGGAAGGAGGCGGCGGCCGCGATGAGCCTTCAGCCTGCCGGGCAGGGGACGTGAACATGGATGACCCTAACAAGGAAGTGATTTAATGTTTCCCTGAORF Start: ATG at 1ORF Stop: TGA at 1873SEQ ID NO:214624 aaMW at 69393.3 kDNOV74a,MAAASPLRDCQAWKDARLPLSTTSNEACKLFDATLTQYVKWTNDKSLGGTEGCLSKLKCG59268-01 Protein SequenceAADPTFVMGHAMATGLVLIGTGSSVKLDKELDLAVKTMVEISRTQPLTRREQLHVSAVETFANGNFPKACELWEQILQDHPTDMLALKFSHDAYFYLGYQEQMRDSVARIYPFWTPDIPLSSYVKGTYSEGLMETNFYDQAEKLAKEAPTLCLQHQHPTDNYWAGKAGCDGARSGNTWALCLQPQADAWSVHTVAHIHEMKAEIKDGLEFMQHSETFWKDSDMLACHNYWIWALYLIEKGLIRRTLFFQGEYEAALTIYDTHILPSLQANDANLDVVDSCSMLYRLQMEGVSVGQRWQDVLPVARKHSRDHILLFNDAHFLMASLGAHDPQTTQELLTTLRDASEYAEGPSRGGGPHPAERCQAFACIISNPDGSVRLALLCLLTDEQTEAGRSPGENCQHLLARDVGLPLCQALVEAEDGNPDRVLELLLPIRYRIVQLGGSNAQRDVFNQLLIHAALWCTSSVHKNVARSLLMERDALKPNSPLTERLTRKAATVHLMQKPSTRQPPLQAALSMEGGGGRDEPSACRAGDVNMDDPKKEGKSLLLRRCCCSGCSVEMEGDLMFP


[0713] Further analysis of the NOV74a protein yielded the following properties shown in Table 74B.
389TABLE 74BProtein Sequence Properties NOV74aPSort0.4328 probability located in mitochondrial matrix space;analysis:0.3000 probability located in microbody (peroxisome);0.1137 probability located in mitochondrial inner membrane;0.1137 probability located in mitochondrial intermembranespaceSignalPNo Known Signal Sequence Predictedanalysis:


[0714] A search of the NOV74a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 74C.
390TABLE 74CGeneseq Results for NOV74aIdentities/NOV74aSimilarities forGeneseqProtein/Organism/LengthResidues/the MatchedExpectIdentifier[Patent #, Date]Match ResiduesRegionValueAAM41338Human polypeptide SEQ ID NO1 . . . 559463/559(82%)0.06269 - Homo sapiens, 478 aa.10 . . . 478 466/559(82%)[WO200153312-A1, 26 JUL2001]AAM39552Human polypeptide SEQ ID NO1 . . . 529434/529(82%)0.02697 - Homo sapiens, 453 aa.1 . . . 439437/529(82%)[WO200153312-A1, 26 JUL2001]AAG02871Human secreted protein, SEQ ID1 . . . 102102/102(100%)1e−52NO: 6952 - Homo sapiens, 104 aa.1 . . . 102102/102(100%)[EP1033401-A2, 6 SEP 2000]AAM40893Human polypeptide SEQ ID NO568 . . . 604 32/37(86%)2e−105824 - Homo sapiens, 746 aa.1 . . . 37 32/37(86%)[WO200153312-A1, 26 JUL2001]AAM40892Human polypeptide SEQ ID NO568 . . . 604 32/37(86%)2e−105823 - Homo sapiens, 746 aa.1 . . . 37 32/37(86%)[WO200153312-A1, 26 JUL2001]


[0715] In a BLAST search of public sequence databases, the NOV74a protein was found to have homology to the proteins shown in the BLASTP data in Table 74D.
391TABLE 74DPublic BLASTP Results for NOV74aNOV74aIdentities/ProteinResidues/Similarities forAccessionMatchthe MatchedExpectNumberProtein/Organism/LengthResiduesPortionValueAAH18918HYPOTHETICAL 45.7 KDA66 . . . 559399/494 (80%)0.0PROTEIN - Homo sapiens 1 . . . 404402/494 (80%)(Human), 404 aa.Q9NWP8KAIA2372 PROTEIN - Homo 1 . . . 352305/352 (86%) e−172sapiens (Human), 336 aa. 1 . . . 310308/352 (86%)3e−61Q9XW02Y54G11A.4 PROTEIN - 4 . . . 556165/557 (29%)Caenorhabditis elegans, 497 aa. 6 . . . 458256/557 (45%)Q9XW01Y54G11A.7 PROTEIN - 4 . . . 347122/347 (35%)7e−53Caenorhabditis elegans, 407 aa. 6 . . . 305177/347 (50%)Q98CS1MLR5032 PROTEIN -60 . . . 553145/496 (29%)1e−43Rhizobium loti (Mesorhizobium46 . . . 435215/496 (43%)loti), 440 aa.


[0716] PFam analysis predicts that the NOV74a protein contains the domains shown in the Table 74E.
392TABLE 74EDomain Analysis of NOV74aIdentities/PfamNOV74aSimilarities forExpectDomainMatch Regionthe Matched RegionValueMonooxygenase: domain225 . . . 410 28/238 (12%)6.41 of 1121/238 (51%)



Example 75

[0717] The NOV75 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 75A.
393TABLE 75ANOV75 Sequence AnalysisSEQ ID NO:2151851 bpNOV75a,CAGCTACAGCAAACATCGTTCGAGATGTCCCACCAAGAGGGCAGCACAGGTGGCTTACCG59549-01 DNA SequenceCAGACTTAGTGACTGAAAGCCTGTTCAGCAGCCCAGAGGAGCAGTCTGGAGTAGCAGCGGTGACGGCGCCCTCCTCACACATTCAAATGGCACCCACAGAGCCATCGACCGGAGATGGTGGTGATACCAGGGATGGTGGTTTCCTGAACGATGCCAGCACAGAAAATCAAAACACAGACTCAGAAAGTTCAAGTGAAGACGTCGAACTTGAAAGCATGGGTGAACGTTTATTTGGTTACCCGTTAGTGGGAGAGGAGACAGAAAGGGAGGAGGAAGAAGAAGAGATGGAGGAGGAAGGGGAGGAGGAACAACAGCCTCCGATGTGTCCACGATGCGCTGGCACCAACCATGATCAGTGTTTGTTAGACGAGGATCAGGCGTTGGAGGAGTGGATTTCCTCAGAGACATCTGCCCTGCCCCGATCTCGCTGGCAAGTCCTTACTGCTCTTCGCCAGCGGCAGCTGGGTTCAAGTGCCCGCTTTGTATATGAGGCCTGTGGGGCAAGAACCTTTGTGCAGCGTTTCCGCCTGCAQTATCTTCTTGGAAGCCATGCCGGTTCTGTCAGTACCATACACTTTAACCAGCGTGGCACCCGACTGGCCAGTAGCGGTGATGACTTAAGGGTGATAGTGTGGGACTGGGTGCGGCAGAAQCCAGTACTGAACTTTGAGAGTGGTCACGATATTAATGTCATCCAGGCTAAGTTCTTTCCTAACTGTGGTGATTCCACTCTGGCCATGTGTGGCCATGATGGACAGGTACGGGTAGCAGAACTAATTAATGCATCATATTGCGAGAATACTAAGCGTGTGGCCAAGCACAGGGGACCTGCCCACGAGTTGGCTCTGGAGCCAGACTCTCCTTATAAGTTCCTCACTTCAGGTGAAGATGCCGTTGTGTTCACCATTGACCTCAGGCAAGACCCGCCAGCTTCAAAAGTTGTGCTAACAAGAGAAAATGATAAGAAAGTCGCACTGTATACAATCTCTATGAATCCTGCCAATATTTACCAATTTGCAGTGGGTGGACATGATCAGTTTGTAAGGATTTATGACCAGAGGAGAATTGATAAGAAAGAAAACAATGGAGTACTCAAGAAATTCACTCCTCATCATCTCGTTTATTGTGATTTCCCAACAAACATCACCTCCGTTGTGTACAGCCACGATCGCACAGAGCTCCTGGCCAGCTACAATGATGAAGATATTTACCTCTTCAACTCCTCTCTCAGTGATGGTGCTCAATATGTTAAGAGATATAAGGGGCACAGAAATAATGACACAATCAAATGTGTTAATTTCTATGGCCCCCGGAGTGAGTTTGTCGTGAGCGGTAGTGATTGTGGGCACGTCTTCTTCTGGGAGAAATCATCCTCCCAGATCATCCAGTTCATGGAGGGGGACAGAGGATATATAGTAAACTGTCTTGAACCCCACCCTTACCTACCTGTGTTGGCGACCAGTGGCCTAGATCAGCATGTCAGCATCTGGACACCCACAGCTAAAACTGCCACTGAGCTTACTGGGTTAAAAGATGTGATTAAGAAGAACAAGCAGGAGCGAGATGAAGACAACTTGAACTATACGGACTCGTTTGACAACCGCATGCTTCGGTTCTTCGTGCCTCACCTGTTACAGAGAGCTCATCAACCCGGCTGGAGAGATCATGGAGCTGAGTTCCCAGATGAAGAAGAGTTGGATGAGTCTTCCAGCACCTCAGATACATCCGAGGAGGAGGGCCAAGATCGAGTGCAGTGCATACCATCCTGAAGGCCTCATATCCAGTCCAGCTAGORF Start: ATG at 25ORF Stop: TGA at 1825SEQ ID NO:216600 aaMW at 67372.4 kDNOV75a,MSHQEGSTGGLPDLVTESLFSSPEEQSGVAAVTAASSDIEMAATEPSTGDGGDTRDGGCG59549-01 Protein SequenceFLNDASTENQNTDSESSSEDVELESMGEGLFGYPLVGEETEREEEEEEMEEEGEEEEQPRMCPRCGGTNHDQCLLDEDQALEEWISSETSALPRSRWQVLTALRQRQLGSSARFVYEACGARTFVQRFRLQYLLGSHAGSVSTTHFNQRGTRLASSGDDLRVTVWDWVRQKPVLNFESGHDINVIQAKFFPNCGDSTLAMCGHDGQVRVAELINASYCENTKRVAKHRGPAHELALEPDSPYKFLTSGEDAVVFTIDLRQDRPASKVVVTRENDKKVGLYTISMNPANIYQFAVGGHDQFVRIYDQRRIDKKENNGVLKKFTPHHLVYCDFPTNITCVVYSHDGTELLASYNDEDTYLFNSSLSDGAQYVKRYKCHRNNDTIKCVNFYGFRSEFVVSGSDCGEVFFWEKSSSQIIQFMECDRGDTVNCLEPHPYLPVLATSGLDQHVRIWTPTAKTATELTCLKDVIKKNKQERDEDNLNYTDSFDNRNLRFFVRHLLQRAHQPGWRDHGAEFPDEEELDESSSTSDTSEEEGQDRVQCIPS


[0718] Further analysis of the NOV75a protein yielded the following properties shown in Table 75B.
394TABLE 75BProtein Sequence Properties NOV75aPSort0.6500 probability located in cytoplasm; 0.1000 probabilityanalysis:located in mitochondrial matrix space; 0.1000 probabilitylocated in lysosome (lumen); 0.0442 probability located inmicrobody (peroxisome)SignalPNo Known Signal Sequence Predictedanalysis:


[0719] A search of the NOV75a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 75C.
395TABLE 75CGeneseq Results for NOV75aNOV75aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAR85870WD-40 domain-contg. Mus 95 . . . 589295/495 (59%) e−179musculus protein-Mus musculus,333 . . . 815372/495 (74%)816 aa. [WO9521252-A2,10 AUG. 1995]AAM73935Human bone marrow expressed 1 . . . 157157/157 (100%)2e−87probe encoded protein SEQ ID NO: 8 . . . 164157/157 (100%)34241-Homo sapiens, 164 aa.[WO200157276-A2, 9 AUG. 2001]AAM61216Human brain expressed single exon 1 . . . 157157/157 (100%)2e−87probe encoded protein SEQ ID NO: 8 . . . 164157/157 (100%)33321-Homo sapiens, 164 aa.[WO200157275-A2, 9 AUG. 2001]AAM34114Peptide #8151 encoded by probe 1 . . . 157157/157 (100%)2e−87for measuring placental gene 8 . . . 164157/157 (100%)expression-Homo sapiens, 164 aa.[WO200157272-A2, 9 AUG. 2001]AAB57007Human prostate cancer antigen408 . . . 600144/194 (74%)2e−80protein sequence SEQ ID NO: 1585- 22 . . . 214162/194 (83%)Homo sapiens, 214 aa.[WO200055174-A1, 21 SEP. 2000]


[0720] In a BLAST search of public sequence databases, the NOV75a protein was found to have homology to the proteins shown in the BLASTP data in Table 75D.
396TABLE 75DPublic BLASTP Results for NOV75aNOV75aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueQ12839H326 PROTEIN-Homo sapiens 1 . . . 600408/604 (67%)0.0(Human), 597 aa. 1 . . . 597471/604 (77%)Q01078PROTEIN PC326-Mus musculus 95 . . . 589295/495 (59%) e−178(Mouse), 747 aa.264 . . . 746372/495 (74%)Q9W091CG8001 PROTEIN-Drosophila 68 . . . 587178/533 (33%)1e−77melanogaster (Fruit fly), 748 aa.209 . . . 711280/533 (52%)Q96E00UNKNOWN (PROTEIN FOR 1 . . . 246141/249 (56%)8e−66MGC: 9478)-Homo sapiens 1 . . . 243173/249 (68%)(Human), 273 aa.Q9M1E5HYPOTHETICAL 54.0 KDA183 . . . 536136/382 (35%)2e−62PROTEIN-Arabidopsis thaliana 42 . . . 419209/382 (54%)(Mouse-ear cress), 481 aa.


[0721] PFam analysis predicts that the NOV75a protein contains the domains shown in the Table 75E.
397TABLE 75EDomain Analysis of NOV75aIdentities/PfamNOV75aSimilarities forExpectDomainMatch Regionthe Matched RegionValueWD40: domain 1 of 7188 . . . 22413/37 (35%) 0.001629/37 (78%)WD40: domain 2 of 7231 . . . 26912/39 (31%)1126/39 (67%)WD40: domain 3 of 7278 . . . 315 9/38 (24%)2.2e+0224/38 (63%)WD40: domain 4 of 7326 . . . 363 8/38 (21%) 8.827/38 (71%)WD40: domain 5 of 7382 . . . 418 5/37 (14%)1227/37 (73%)WD40: domain 6 of 7429 . . . 466 6/38 (16%)1826/38 (68%)WD40: domain 7 of 7473 . . . 50911/37 (30%) 0.5122/37 (59%)



Example 76

[0722] The NOV76 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 76A.
398TABLE 76ANOV76 Sequence AnalysisSEQ ID NO:2177497 bpNOV76a,ATGGTCTTGCTTCTTTGTCTATCTTGTCTGATTTTCTCCTGTCTGACCTTTTCCTGGTCG59641-01 DNA SequenceTAAAAATCTGGGGGAAAATGACGGACTCCAAGCCGATCACCAAGAGTAAATCAGAAGCAAACCTCATCCCGAGCCAGGAGCCCTTTCCAGCCTCTGATAACTCAGGGGAGACACCGCAGAGAAATGGGGAGGGCCACACTCTGCCCAACACACCCAGCCAGGCCGAGCCAGCCTCCCACAAAGGCCCCAAAGATGCCGGTCGGCGGAGAAACTCCCTACCACCCTCCCACCAGAAGCCCCCAAGAAACCCCCTTTCTTCCAGTGACGCAGCACCCTCCCCAGAGCTTCAAGCCAACGCGACTGGGACACAAGGTCTGGAGGCCACAGATACCAATGGCCTGTCCTCCTCAGCCAGGCCCCAGGGCCAGCAAGCTGGCTCCCCCTCCAAAGAAGACAAGAAGCAGGCAAACATCAAGAGGCAGCTGATGACCAACTTCATCCTGGGCTCTTTTGATGACTACTCCTCCGACGAGGACTCTGTTGCTGGCTCATCTCGTGAGTCTACCCCGAAGGGCAGCCGGCCCAGCTTGGGGGCCCTGTCCCTGGAGGCTTATCTGACCACAAGGCCGAGCATGTCGGGACTCCACCTGGTGAAGAGGGGACGGGAACACAAGAAGCTGGACCTGCACAGAGACTTTACCGTGGCTTCTCCCGCTGAGTTTGTCACACGCTTTGGGGGGGATCGGGTCATCGAGAAGGTGCTTATTGCCAACAACGGCATTGCCGCCGTGAAGTGCATGCGCTCCATCCGCAGGTGGGCCTATGAGATGTTCCGCAACGAGCGGGCCATCCGGTTTGTTGTGATGGTGACCCCCGAGGACCTTAAGGCCAACGCAGAGTACATCAAGATGGCGGATCATTACGTCCCCGTCCCAGGAGGGCCCAATAACAACAACTATGCCAACGTGGAGCTGATTGTGGACATTGCCAAGAGAATCCCCGTGCAGCCGGTGTGGGCTGGCTGGGGCCATGCTTCAGAAAACCCTAAACTTCCGGAGCTGCTGTGCAAGAATGGAGTTGCTTTCTTAGGCCCTCCCAGTGAGGCCATGTGGGCCTTAGGAGATAAGATCGCCTCCACCGTTGTCGCCCAGACGCTACAGGTCCCAACCCTGCCCTGGAGTGGAAGCGGCCTGACAGTGGAGTGGACAGAAGATGATCTGCAGCAGGGAAAAAGAATCAGTGTCCCAGAAGATGTTTATGACAAGGGTTGCGTGAAAGACGTAGATGAGGGCTTGGAGGCAGCAGAAACAATTGGTTTTCCATTGATCATCAAAGCTTCTGAAGGTGGCGGAGGGAAGGGAATCCGGAAGGCTGAGAGTGCGGAGGACTTCCCGATCCTTTTCAGACAAGTACAGAGTGAGATCCCAGGCTCGCCCATCTTTCTCATGAAGCTGGCCCAGCACGCCCGTCACCTGGAAGTTCAGATCCTCGCTGACCAGTATGGGAATGCTGTGTCTCTGTTTGGTCGCGACTGCTCCATCCAGCGGCGGCATCAGAAGATCGTTGAGGAAGCACCGGCCACCATCGCCCCGCTGGCCATATTCGAGTTCATGGAGCAGTGTGCCATCCGCCTGGCCAAGACCGTGGGCTATGTGAGTGCAGGGACAGTGGAATACCTCTATAGTCAGGATGGCAGCTTCCACTTCTTGGAGCTGAATCCTCGCTTGCAGGTGGAACATCCCTGCACAGAAATGATTGCTGATGTTAATCTGCCGGCCGCCCAGCTACAGATCGCCATGGGCGTGCCACTGCACCGGCTGAAGGATATCCGGCTTCTGTATGGAGAGTCACCATGGGGAGTGACTCCCATTTCTTTTGAAACCCCCTCAAACCCTCCCCTCGCCCGAGGCCACGTCATTGCCGCCAGAATCACCAGCGAAAACCCAGACGAGGGTTTTAAGCCGAGCTCCGGGACTGTCCAGGAACTGAATTTCCGGAGCAGCAAGAACGTGTGGGGTTACTTCAGCGTGGCCGCTACTGGAGCCCTGCACCAGTTTGCGGATTCCCAATTTGGGCACTGCTTCTCCTGGGGAGAGAACCGGGAAGAGGCCATTTCGAACATGGTGGTGGCTTTGAAGGAACTGTCCATCCGAGGCGACTTTAGGACTACCGTGGAATACCTCATTAACCTCCTGGACACCGAGAGCTTCCAGAACAACGACATCGACACCGGGTGGTTGGACTACCTCATTGCTGAGAAAGTGCAGGCGGAGAAACCGGATATCATGCTTGGGGTGGTATGCGGGGCCTTGAACGTGGCCGATGCGATGTTCAGAACGTGCATGACAGATTTCTTACACTCCCTCCAAAGGCGCCAGGTCCTCCCAGCGGATTCACTACTGAACCTCGTAGATGTGGAATTAATTTACGGAGGTGTTAAGTACATTCTCAAGGTGGCCCGGCAGTCTCTGACCATGTTCGTTCTCATCATGAATGGCTCCCACATCGAGATTGATGCCCACCGCCTGAATGATCCGGGGCTCCTCCTCTCCTACAATGGGAACAGCTACACCACCTACATGAAGGAAGAGGTTGACACTTACCGAATTACCATCGGCAATAAGACGTGTGTGTTTGAGAAGGAGAACGATCCTACAGTCCTGAGATCCCCCTCGGCTGGGAAGCTGACACAGTACACAGTGGAGGATGGGGGCCACGTTGAGGCTGGGAGCAGCTACGCTGAGATGGAGGTGATGAAGATGATCATGACCCTGAACGTTCAGGAAAGAGGCCGGGTGAAGTACATCAAGCGTCCAGGTGCCGTGCTGGAAGCAGGCTGCGTGGTGGCCAGGCTGGAGCTCGATGACCCTTCTAAAGTCCACCCGGCTCAACCGTTCACAGGAGAACTCCCTGCCCAGCAGACACTGCCCATCCTCGGAGAGAAACTGCACCACGTCTTCCACAGCGTCCTGGAAAACCTCACCAACCTCATGAGTCGCTTTTCTCTGCCAGACCCCGTTTTTAGCATAAAGCTGAAGGAGTGGGTGCAGAAGCTCATGATGACCCTCCGGCACCCGTCACTGCCGCTGCTGGAGCTCCAGGAGATCATGACCAGCGTGGCAGGCCGCATCCCCGCCCCTGTGGAGAAGTCTGTCCGCAGGGTGATGGCCCAGTATGCCAGCAACATCACCTCGGTGCTGTGCCAGTTCCCCACCCAGCAGATAGCCACCATCCTGGACTGCCATCCAGCCACCCTGCAGCGGAAGGCTGATCGAGAGGTCTTCTTCATCAACACCCACAGCATCGTGCAGTTGGTCCAGAGATACCGCAGCGCGATCCGCGCCTATATGAAAACAGTGGTGTTGGATCTCCTGAGAAGATACTTGCGTGTTGAGAGCAACGCAAGACATGCTGATGCCAACACCAGTGGGATGGTGGGGGGCGTGAGGAGCCTGAGCTTTACCTCTGTGTGGTGTTTTGTCTCCCCCGAATCCCACTACGACAAGTGTGTGATAAACCTCAGGGAGCAGTTCAAGCCAGACATGTCCCAGGTGCTGGACTGCATCTTCTCCCACGCACAGGTGGCCAAGAAGAACCAGCTGGTGATCATGTTGATCGATGAGCTGTGTGGCCCAGACCCTTCCCTGTCGGACGAGCTGATCTCCATCCTCAACGAGCTCACTCAGCTGAGCAAAAGCGAGCACTGCAAAGTGGCCCTCAGAGCCCGGCAGATCCTGATTGCCTCCCACCTCCCCTCCTACGAGCTGCGGCATAACCACGTGGAGTCCATTTTCCTGTCTGCCATTGACATCTACGCCCACCAGTTCTGCCCCCACAACCTCAAGAAATTAATACTTTCGGAAACAACCATCTTCGACGTCCTGCCTACTTTCTTCTATCACGCAAACAAAGTCGTGTGCATGGCGTCCTTGGAGCTTTACGTGCCGAGGGGCTACATCGCCTATGAGTTAAACAGCCTGCAGCACCGGCAGCTCCCGGACGGCACCTGCGTGGTAGAATTCCAGTTCATCCTGCCGTCCTCCCACCCAAACCGGATGACCGTGCCCATCACCATCACCAACCCTGACCTGCTGAGGCACAGCACAGAGCTCTTCATGCACAGCGGCTTCTCCCCACTGTGCCAGCGCATGGGAGCCATGGTAGCCTTCAGGAGATTCGAGCACTTCACCAGAAATTTTGATGAAGTCATCTCTTGCTTCGCCAACGTCCCCAAAGACACCCCCCTCTTCACCGAGGCCCGCACCTCCCTATACTCCGAGGATGACTGCAAGAGCCTCAGAGAAGAGCCCATCCACATTCTGAATGTGTCCATCCAGTGTGCAGACCACCTGGAGGATGAGGCACTGGTGCCGATTTTACGGACATTCGTACAGTCCAAGAAAAATATCCTTGTGGATTATCCACTCCGACGAATCACATTCTTGATTGCCCAAGACTTTGCAGAAGATCGCATTTACCGTCACTTCGAACCTGCCCTGGCCTTCCAGCTGGAACTTAACCGGATGCGTAACTTCGATCTGACCGCCGTGCCCTGTGCCAACCACAAGATGCACCTTTACCTGGGTGCTGCCAAGGTGAAGGAAGGTGTGGAAGTGACGGACCATAGGTTCTTCATCCGCGCCATCATCAGGCACTCTGACCTGATCACAAAGGAAGCCTCCTTCGAATACCTGCAGAACGAGGGTGAGCGGCTGCTCCTGGAGGCCATGGACGAGCTGGAGGTGGCGTTCAATAACACCAGCGTGCGCACCGACTGCAACCACATCTTCCTCAACTTCGTGCCCACTGTCATCATGGACCCCTTCAAGATCGAGGAGTCCGTGCGCTACATGGTTATGCGCTACGGCAGCCGGCTGTGGAAACTCCGTGTGCTACAGGCTGAGGTCAAGATCAACATCCGCCAGACCACCACCGGCAGTGCCGTTCCCATCCGCCTGTTCATCACCAATGAGTCGGGCTACTACCTGGACATCAGCCTCTACAAAGAAGTGACTGACTCCACATCTGGAAATATCATCTTTCACTCCTTCGGCAACAAGCAAGGGCCCCAGCACGGGATGCTGATCAATACTCCCTACGTCACCAAGGATCTGCTCCAGGCCAAGCGATTCCACGCCCAGACCCTGGGAACCACCTACATCTATGACTTCCCCGAAATGTTCACCCAGGCAAGTCCGGCGGCTCACACGCGGGTACATGTGCACAATGTGCAGCCTCTCTTTAAACTGTGGGGCTCCCCAGACAAGTATCCCAAACACATCCTGACATACACTCAATTAGTGTTGGACTCTCAGGCCCAGCTGGTCCAGATGAACCGACTTCCTGGTGGAAATGAGGTGCCCATGGTGGCCTTCAAAATGAGCTTTAAGACCCAGGAGTACCCGGAAGGACGGGATGTGATCGTCATCGGCAATGACATCACCTTTCGCATTGGATCCTTTGGCCCTGGAGAGCACCTTCTGTACCTGCCGGCATCCGAGATCCCCCGCGCAGAGGGCATTCCCAAAATTTACGTGGCAGCCAACAGTGGCGCCCGTATTCGCATGGCAGAGGAGATCAAACACATGTTCCACGTGGCTTGGGTGGACCCAGAAGACCCCCACAAAAAAAAAAAAACAGTGGCTTTCAGTGCAGGGAACTGGATTCGTAGCCTCACTAAAGTATTTTTTAAGGGATTTAAATACCTGTACCTGACTCCCCAAGACTACACCACAATCAGCTCCCTGAACTCCGTCCACTGTAAACACATCGAGGAAGGAGGAGAGTCCAGATACATGATCACGGATATCATCGGGAAGGATGATGGCTTGGGCGTGGAGAATCTGAGGGGCTCAGGCATGATTGCTGGGGAGTCCTCTCTGGCTTACGAAGAGATCGTCACCATTAGCTTGGTGACCTGCCGAGCCATTGGGATTGGGGCCTACTTGGTGAGGCTGGGCCAGCGAGTGATCCAGGTGGAGAATTCCCACATCATCCTCACAGGAGCAAGTGCTCTCAACAAGGTCCTGGGAAGAGAGGTCTACACATCCAACAACCAGCTGGGTGGCGTTCAGATCATGCATTACAATGGTGTCTCCCACATCACCGTGCCAGATGACTTTGAGGGGGTTTATACCATCCTGGAGTGGCTGTCCTATATGCCAAAGGATAATCACAGCCCTGTCCCTATCATCACACCCACTGACCCCATTGACAGAGAAATTGAATTCCTCCCATCCAGAGCTCCCTACGACCCCCGGTGGATGCTTGCAGGAAGGCCTCACCCAACTCTGAAGGGAACGTGGCAGAGCGGATTCTTTGACCACGGCAGTTTCAAGGAAATCATGGCACCCTGGGCGCAGACCGTGGTGACAGGACGAGCAAGGCTTGGGGGGATTCCCGTGGGAGTGATTGCTGTGGAGACACGGACTGTGGAGGTGGCAGTCCCTGCACACCCTGCCAACCTGGATTCTGAGGCCAAGATAATTCAGCAGGCAGGACAGGTGTGGTTCCCAGACTCAGCCTACAAAACCGCCCAGGCCCTCAAGGACTTCAACCGGGAGAAGTTCCCCCTGATGATCTTTGCCAACTGGAGGGCGTTCTCCGGTGGCATGAAAGACATGTATGACCAGGTGCTGAAGTTTGGAGCCTACATCGTGGACGGCCTTAGACAATACAAACAGCCCATCCTGATCTATATCCCGCCCTATGCGGAGCTCCGGGGAGGCTCCTGGGTGGTCATAGATGCCACCATCAACCCGCTGTGCATAGAAATGTATGCAGACAAAGAGAGCAGGGGTGGTGTTCTGGAACCAGAGGGGACAGTGGAGATTAAGTTCCGAAAGAAAGATCTGATAAAGTCCATGAGAAGGATCGATCCAGCTTACAAGAAGCTCATGGAACAGCTAGGGGAACCTGATCTCTCCGACAAGGACCGAAAGGACCTGGAGGGCCGGCTAAAGGCTCGCGAGGACCTGCTGCTCCCCATCTACCACCAGGTGGCGGTGCAGTTCGCCGACTTCCATGACACACCCGGCCGGATGCTGGAGAAGGGCGTCATATCTGACATCCTGGAGTGGAAGACCGCACGCACCTTCCTGTATTGGCGTCTGCGCCGCCTCCTCCTGGAGGACCAGGTCAAGCAGGAGATCCTGCAGGCCAGCGGGGAGCTGAGTCACGTGCATATCCAGTCCATGCTGCGTCGCTGGTTCGTGGAGACGGAGGGGGCTGTCAAGGCCTACTTGTGGGACAACAACCAGGTGGTTGTGCAGTGGCTGGAACAGCACTGGCAGGCAGGGGATGGCCCGCGCTCCACCATCCGTGAGAACATCACGTACCTGAAGCACGACTCTGTCCTCAAGACCATCCGAGGCCTGGTTGAAGAAAACCCCGAGGTGGCCGTGGACTGTGTGATATACCTGAGCCAGCACATCAGCCCAGCTGAGCGGGCGCAGGTCGTTCACCTGCTGTCTACCATGGACAGCCCGGCCTCCACCTGAORF Start: ATG at 1ORF Stop: TGA at 7495SEQ ID NO:2182498 aaMW at 280484.4 kDNOV76a,MVLLLCLSCLIFSCLTFSWLKIWGKMTDSKPITKSKSEANLIPSQEPFPASDNSGETPCG59641-01 Protein SequenceQRNGEGHTLPKTPSQAEPASHKGPKDAGRRRNSLPPSHQKPPRNPLSSSDAAPSPELQANGTGTQGLEATDTNGLSSSARPQGQQAGSPSKEDKKQANIKRQLMTNFILGSFDDYSSDEDSVAGSSRESTRKGSRASLGALSLEAYLTTRPSMSGLHLVKRGREHKKLDLHRDFTVASPAEFVTRFGGDRVIEKVLIANNGIAAVKCMRSIRRWAYEMFRNERAIRFVVMVTPEDLKANAEYIKMADHYVPVPGGPNNNNYANVELIVDIAKRIPVQAVWAGWGHASENPKLPELLCKNGVAFLGPPSEAMWALGDKIASTVVAQTLQVPTLPWSGSGLTVEWTEDDLQQGKRISVPEDVYDKGCVKDVDEGLEAAERTGFPLMIKASEGGGGKGIRKAESAEDFPILFRQVQSEIPGSPIFLMKLAQHARHLEVQILADQYGNAVSLFGRDCSIQRRHQKIVEEAPATIAPLAIFEFMEQCAIRLAKTVGYVSAGTVEYLYSQDGSFHFLELNPRLQVEHPCTEMIADVNLPAAQLQIAMGVPLHRLKDIRLLYGESPWGVTPISFETPSNPPLARGBVIAARITSENPDEGFKPSSGTVQELNFRSSKNVWGYFSVAATGGLHEFADSQFGHCFSWGENREEAISNMVVALKELSIRGDFRTTVEYLINLLETESFQNNDIDTGWLDYLIAEKVQAEKPDIMLGVVCGALNVADAMFRTCMTDFLHSLERGQVLPADSLLNLVDVELIYGGVKYILKVARQSLTMFVLIMNGCHIEIDAHRLNDGGLLLSYNGNSYTTYMKEEVDSYRITIGNKTCVFEKENDPTVLRSPSAGKLTQYTVEDGGHVEAGSSYAEMEVMKMIMTLNVQERGRVKYIKRPGAVLEAGCVVARLELDDPSKVHPAEPFTGELPAQQTLPILGEKLHQVFHSVLENLTNVMSGFCLPEPVFSIKLKEWVQKLMMTLRHPSLPLLELQEIMTSVAGRIPAPVEKSVRRVMAQYASNITSVLCQFPSQQIATILDCKAATLQRKADREVFFINTQSIVQLVQRYRSGIRCYMKTVVLDLLRRYLRVESKARDADANTSGMVGGVRSLSFTSVWCFVSPESHYDKCVINLREQFKPDMSQVLDCIFSHAQVAKKNQLVIMLIDELCGPDPSLSDELISILNELTQLSKSEECKVALRARQILIASHLPSYELRHNQVESIFLSAIDMYGHQFCPENLKKLILSETTIFDVLPTFFYHANKVVCMASLEVYVRRGYIAYELNSLQHRQLPDGTCVVEFQFMLPSSEPNRMTVPISITNPDLLRHSTELFMDSGFSPLCQRNGANVAFRRFEDFTRNFDEVISCFANVPKDTPLFSEARTSLYSEDDCKSLREEPIHILNVSIQCADHLEDEALVPILRTFVQSKKNILVDYGLRRITFLIAQEFAEDRIYRHLEPALAFQLELNRNRNFDLTAVPCANHKMHLYLGAAKVKEGVEVTDHRFFIRAIIRHSDLITKEASFEYLQNECERLLLEAMDELEVAFNNTSVRTDCNBIFLNFVPTVIMDPFKIEESVRYMVMRYGSRLWKLRVLQAEVKINIRQTTTGSAVPIRLPITNESGYYLDISLYKEVTDSRSGNIMFHSFGNKQGPQHGMLINTPYVTKDLLQAKRFQAQTLGTTYIYDfPEMFRQASPAAQTRVHVHNVQALFKLWGSPDKYPKDILTYTELVLDSQGQLVEMNRLPGGNEVGMVAFKMRFKTQEYPEGRDVIVIGNDITFRIGSFGPGEDLLYLRASEMARAEGIPKIYVAANSGARIGMAEEIKHMFHVAWVDPEDPHKKKKTVAFSAGNWIRSLTKVPFKGFKYLYLTPQDYTRISSLNSVHCKHIEEGGESRYMITDIIGKDDGLGVENLRGSGMIAGESSLAYEEIVTISLVTCRAIGIGAYLVRLGQRVIQVENSHIILTGASALNKVLCREVYTSNNQLCGVQIMHYNGVSHITVPDDFEGVYTILEWLSYMPKDNESPVPIITPTDPIDREIEFLPSRAPYDPRWMLAGRPHPTLKGTWQSGPEDEGSFKEIMAPWAQTVVTGRARLGGIPVGVIAVETRTVEVAVPADPANLDSEAKIIQQAGQVWFPDSAYKTAQAVKDFNREKLPLMIFANWRGFSGGMKDMYDQVLKPGAYIVDGLRQYKQPILIYIPPYAELRGGSWVVIDATINPLCIEMYADKESRGGVLEPEGTVEIKFRKKDLIKSMRRIDPAYKKLMEQLGEPDLSDKDRKDLEGRLKAREDLLLPIYHQVAVQFADFHDTPGRMLEKGVISDILEWKTARTFLYWRLRRLLLEDQVKQEILQASGELSHVHIQSMLRRWFVETEGAVKAYLWDNNQVVVQWLEQHWQAGDGPRSTIRENITYLKHDSVLKTIRGLVEENPEVAVDCVIYLSQHISPAERAQVVHLLSTMDSPAST


[0723] Further analysis of the NOV76a protein yielded the following properties shown in Table 76B.
399TABLE 76BProtein Sequence Properties NOV76aPSort0.6850 probability located in endoplasmic reticulumanalysis:(membrane); 0.6400 probability located in plasmamembrane; 0.4600 probability located in Golgibody; 0.1000 probability located in endoplasmicreticulum (lumen)SignalPLikely cleavage site between residues 25 and 26analysis:


[0724] A search of the NOV76a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 76C.
400TABLE 76CGeneseq Results for NOV76aNOV76aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAU32848Novel human secreted protein 26 . . . 24982316/2555 (90%)0.0#3339-Homo sapiens, 2486 aa. 1 . . . 24862339/2555 (90%)[WO200179449-A2,25 OCT. 2001]AAR05707Acetyl-CoA-carboxylase-Gallus163 . . . 24981728/2375 (72%)0.0sp, 2324 aa. [JP02057179-A, 17 . . . 23242003/2375 (83%)26 FEB. 1990]AAB86033Bovine acetyl-coenzyme A204 . . . 24971719/2342 (73%)0.0carboxylase−alpha protein 14 . . . 22881969/2342 (83%)fragment-Bos taurus, 2288 aa.[DE19946173-A1, 5 APR. 2001]AAR98811Erysiphe graminis acetyl235 . . . 24901045/2326 (44%)0.0coenzyme A carboxylase- 42 . . . 22711432/2326 (60%)Erysiphe graminis f.sp.hordei,2273 aa. [FR2727129-A1,24 MAY 1996]AAY24150Candida albicans acetyl CoA239 . . . 24891015/2300 (44%)0.0carboxylase-Candida albicans, 88 . . . 22691396/2300 (60%)2270 aa. [WO9932635-A1,1 JUL. 1999]


[0725] In a BLAST search of public sequence databases, the NOV76a protein was found to have homology to the proteins shown in the BLASTP data in Table 76D.
401TABLE 76DPublic BLASTP Results for NOV76aNOV76aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueO00763Acetyl-CoA carboxylase 2 (EC 1 . . . 24982349/2528 (92%)0.06.4.1.2) (ACC-beta) [Includes: 1 . . . 24832384/2528 (93%)Biotin carboxylase (BC 6.3.4.14)]-Homo sapiens (Human), 2483 aa.O70151ACETYL-COA CARBOXYLASE- 1 . . . 24972068/2524 (81%)0.0Rattus norvegicus (Rat), 2456 aa. 1 . . . 24552224/2524 (87%)CAA48770ACETYL-COA CARBOXYLASE163 . . . 24981921/2390 (80%)0.0(EC 6.4.1.2)-Homo sapiens 17 . . . 23392086/2390 (86%)(Human), 2339 aa.P11029Acetyl-CoA carboxylase (EC163 . . . 24981732/2375 (72%)0.06.4.1.2) (ACC) [Includes: Biotin 17 . . . 23242004/2375 (83%)carboxylase (EC 6.3.4.14)]-Gallus gallus (Chicken), 2324 aa.P11497Acetyl-CoA carboxylase 1 (EC163 . . . 24971736/2396 (72%)0.06.4.1.2) (ACC-alpha) [Includes: 17 . . . 23451993/2396 (82%)Biotin carboxylase (BC 6.3.4.14)]-Rattus norvegicus (Rat), 2345 aa.


[0726] PFam analysis predicts that the NOV76a protein contains the domains shown in the Table 76E.
402TABLE 76EDomain Analysis of NOV76aIdentities/PfamNOV76aSimilarities forExpectDomainMatch Regionthe Matched RegionValueCPSase_L_chain: 249 . . . 372 49/132 (37%)2.2e−57domain 1 of 1CPSase_L_D2: 374 . . . 619102/253 (40%)6.6e−118domain 1 of 1218/253 (86%)Biotin_carb_C: 640 . . . 747 40/118 (34%)1.9e−53domain 1 of 1100/118 (85%)biotin_lipoyl: 885 . . . 951 22/75 (29%)6.5e−17domain 1 of 1 56/75 (75%)Carboxyl_trans:1783 . . . 1878 31/100 (31%)7.4e−34domain 1 of 2 88/100 (88%)GTP_cyclohydroI:2287 . . . 2304 6/18 (33%)6.6domain 1 of 1 13/18 (72%)Carboxyl_trans:1897 . . . 2374191/504 (38%)4.1e−258domain 2 of 2447/504 (89%)



Example 77

[0727] The NOV77 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 77A.
403TABLE 77ANOV77 Sequence AnalysisSEQ ID NO: 2191624 bpNOV77a,CGCGCGCCGGGGATGGAGCCGCAGCCCGGCGGCGCCCGGAGCTGCCGGCGCGGGGCCCCG59630-01 DNA SequenceCCGGCGGCGCCTGCGAGCTGGGCCCGGCGGCCGAGGCGGCGCCCATGAGCCTCGCCATCCACAGCACCACGGGCACCCGCTACGACCTGGCCGTGCCGCCCGACGAGACGGTGGAGGGGCTGCGCAAGCGGTTGTCCCAGCGCCTCAAAGTGCCCAAGGAGCGCCTGGCTCTTCTCCACAAAGACACGCGGCTCAGTTCGGGGAAGCTGCAGGAGTTCGGCGTGGGTGATGGCAGCAAGCTGACCTTGGTACCCACCGTGGAAGCGGGCCTCATGTCTCAGGCCTCAAGGCCGGAACAGTCCGTGATGCAAGCTCTCGAGAGTCTCACGGAGACGCAGCCCCCAGCGGCGCCCGGGCCGGGCCGGGCTGGCGGAGGAGGCTTCCGGAAATACAGATTCATTTTATTTAAGCGTCCGTGGCACCGACAGGGACCCCAGAGCCCAGAGAGGGGCGGCGAGAGGCCCCAGGTCAGTGACTTCCTGTCGGGCCGTTCGCCACTGACACTGGCCTTGCGTGTGGGCGACCACATGATGTTCGTGCAGCTGCAGCTCGCGGCCCAGCACGCTCCACTGCAACACCGCCATGTGCTGGCCGCTGCGGCCGCCGCCGCTGCTGCGCGGGGGGACCCCAGCATAGCCTCCCCCGTGTCCTCGCCCTGCCGGCCGGTGTCCAGTGCCGCCCGAGTCCCCCCGGTGCCCACCAGCCCGTCCCCTGCATCTCCCTCGCCCATCACAGCCGGCTCCTTCCGGTCCCACGCAGCCTCCACCACCTGCCCGGAGCAGATGGACTGCTCCCCCACGGCCAGCAGCAGTGCCAGTCCTGGTGCCAGCACCACGTCTACCCCAGGGGCCAGCCCTGCCCCCCGCTCCCGAAAACCCGGCGCCGTCATCGAGAGCTTTGTGAATCACGCCCCGGGGGTCTTCTCAGGGACCTTCTCTGGCACGCTACACCCCAACTGCCAAGACAGCAGCGGGCGGCCGCGGCGTGACATCGGCACCATCCTGCAGATCCTGAACGACCTCCTGAGCGCCACCCGGCACTACCAGGGCATGCCCCCTTCGCTGGCCCAGCTCCGCTGCCACGCCCAGTGCTCCCCGGCCTCACCGGCCCCCGACCTGGCCCCCAGAACTACCTCCTGCGAGAAGCTCACGGCTGCCCCCTCAGCCTCCCTGCTGCAGGGCCAGAGCCAGATCCGCATGTGCAAGCCCCCGGGTGACCGGCTTCGGCAGACAGAAAACCGCGCCACGCGCTGCAAGGTGGAACGGCTGCAGCTGCTTCTGCAGCAGAAACGGCTCCGTAGAAAGGCCCGGCGGGACGCGCGGGGTCCGTACCACTGGTCACCCAGCCGCAAGGCCGGCCGCAGCGACAGCAGTAGCAGCGGGGGCGGCGGCAGCCCCAGCGAGGCCTCCGGCTTGGGCCTCGACTTCGAGGACTCCGTGTGGAAGCCAGAAGTCAACCCTGACATCAAGTCAGAGTTCGTGGTGGCTTAGGATCTTCGGATCGGCCACCCTCGCCCCTCGCACCCCAGCCCAGGGCGGCGGGGACTCCGAGAGCCCCGGAGAGAACORF Start: ATG at 13ORF Stop: TAG at 1546SEQ ID NO: 220511 aaMW at 53949.3 kDNOV77a,MEPQPGGARSCRRGAPGGACELGPAAEAAPMSLAIHSTTGTRYDLAVPPDETVEGLRKCG59630-01 Protein SequenceRLSQRLKVPKERLALLHKDTRLSSGKLQEFGVGDGSKLTLVPTVEAGLMSQASRPEQSVMQALESLTETQPPAAPGPGRAGGGGFRKYRFILFKRPWHRQGPQSPERGGERPQVSDFLSGRSPLTLALRVGDHMMFVQLQLAAQHAPLQHRHVLAAAAAAAAARGDPSIASPVSSPCRPVSSAARVPPVPTSPSPASPSPITAGSFRSHAASTTCPEQMDCSPTASSSASPGASTTSTPGASPAPRSRKPGAVIESFVNHAPGVFSGTFSGTLHPNCQDSSGRPRRDIGTILQILNDLLSATRHYQGMPPSLAQLRCHAQCSPASPAPDLAPRTTSCEKLTAAPSASLLQGQSQIRMCKPPGDRLRQTENRATRCKVERLQLLLQQKRLRRKARRDARGPYHWSPSRKAGRSDSSSSGGGGSPSEASGLGLDFEDSVWKPEVNPDIKSEFVVA


[0728] Further analysis of the NOV77a protein yielded the following properties shown in Table 77B.
404TABLE 77BProtein Sequence Properties NOV77aPSort0.3000 probability located in microbody (peroxisome);analysis:0.3000 probability located in nucleus; 0.1526 probabilitylocated in lysosome (lumen); 0.1000 probability located inmitochondrial matrix spaceSignalPNo Known Signal Sequence Predictedanalysis:


[0729] A search of the NOV77a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 77C.
405TABLE 77CGeneseq Results for NOV77aNOV77aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAB56832Human prostate cancer antigen267 . . . 493189/227 (83%)e−104protein sequence SEQ ID NO: 1410- 1 . . . 227195/227 (85%)Homo sapiens, 236 aa.[WO200055174-A1, 21 SEP. 2000]


[0730] In a BLAST search of public sequence databases, the NOV77a protein was found to have homology to the proteins shown in the BLASTP data in Table 77D.
406TABLE 77DPublic BLASTP Results for NOV77aNOV77aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueQ9JJJ6MIDNOLIN-Mus musculus 1 . . . 511475/514 (92%)0.0(Mouse), 508 aa. 1 . . . 508486/514 (94%)Q96BW8SIMILAR TO MIDNOLIN-338 . . . 511174/174 (100%)2e−97Homo sapiens (Human), 177 aa 4 . . . 177174/174 (100%)(fragment).Q9W2S4CG9732 PROTEIN-Drosophila213 . . . 363 58/155 (37%)6e−18melanogaster (Fruit fly), 989 aa.524 . . . 677 80/155 (51%)AAL40834BPLF1-Human herpesvirus 4200 . . . 406 64/223 (28%)2e−07(Epstein-Barr virus), 3179 aa.320 . . . 530 95/223 (41%)Q9BKV7PPG3-Leishmania major, 1325213 . . . 328 37/121 (30%)2e−06aa.984 . . . 1104 66/121 (53%)


[0731] PFam analysis predicts that the NOV77a protein contains the domains shown in the Table 77E.
407TABLE 77EDomain Analysis of NOV77aIdentities/PfamNOV77aSimilarities forExpectDomainMatch Regionthe Matched RegionValueubiquitin: 31 . . . 9919/79 (24%)0.00033domain 1 of 146/79 (58%)PI3_PI4_kinase:411 . . . 427 7/18 (39%)1.5domain 1 of 114/18 (78%)



Example 78

[0732] The NOV78 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 78A.
408TABLE 78ANOV78 Sequence AnalysisSEQ ID NO: 2211034 bpNOV78aCCACCGCCACAGCTGCCAGCATGTCTGGCCCAGACATCAAGACGCCGACCGCCATCCACG59561-01 DNA SequenceGATCTGCCGGATTATGCGGGACGCTAATGTGGCCCGCAATGTCTACGGCGGGACCATCCTGAAGATGATCAAAGAGGCGGGCGCCATCATCAGCACCCGGCATTGCAATCCGCAGAACGGGGATCGCTGTGTGGCCGCTCTGGCTCGGGTCGAGTGCACCCACTTCCTGTGGCCCATGTGCATCGGTGAGGTGGCCCACGTCAGCGCGGAGATCACCTACACCTCCAAGCACTCTGTGGAGGTGCAGGTCAACATGATGTCCGAAAACATCCTCACAGGTGCCAAAAAGCTGACCAATAAGGCCACCCTCTGGTATGCGCCCCTGTCGCTGACGAACGTGGACAAGGTCCTCGAAGAGCCTCCTGTTGTGTATTTCCGGCAGGAGCAGGAGGAGGAGGGCCAGAAGCGGTACAAAACCCAGAAGCTGGAGCGCATGGAGACCAACTGGAGGAACGGGGACATCGTCCAGCCAGTCCTCAACCCAGAGCCGAACACTGTCAGCTACAGCCAGTCCAGCTTGATCCACCTGGTGGGGCCTTCAGACTGTACCCTGCACAGCTTCGTGCATGAAGGGGTGACCATGAAGGTCATGGACGAGGTCGCCGGGATCTTGGCTGCACGCCACTGCAAGACCAACCTCGTCACAGCCTCCATGGAGGCCATTAATTTTGACAACAAGATCAGAAAAGGCTGCATCAAGACCATCTCCGGACGCATGACCTTCACGAGCAATAAGTCCGTAGAGATCGAGGTCTTGGTGGATGCCGACTGTGTTGTGGACAGCTCTCAGAAGCGCTACAGGGCCGCCAGTGTCTTCACCTATGTGTCGCTGAGCCAGGAAGGCAGGTCGCTGCCCATGCCCCAGCTCGTGCCGGAGACCCAGGACGAGAAGGGCTTTGAGGCCTGGCTCGGTGGCTCACGCCTATAATCCCAGCACTTTAGGATGCTGAGGCAGGCGGATCACTTGACGTCAGGAORF Start: ATG at 21ORF Stop: TAA at 984SEQ ID NO: 222321 aaMW at 35738.7 kDNOV78a,MSGPDIKTPTAIQICRIMRDANVARNVYGGTILKMIKEAGAIISTRHCNPQNGDRCVACG59561-01 Protein SequenceALARVECTHFLWPMCIGEVAHVSAEITYTSKHSVEVQVNMMSENILTGAKKLTNKATLWYAPLSLTNVDKVLEEPPVVYFRQEQEEEGQKRYKTQKLERMETNWRNGDIVQPVLNPEPNTVSYSQSSLIHLVGPSDCTLHSFVHEGVTMKVMDEVAGILAARHCKTNLVTASMEAINFDNKIRKGCIKTISGRMTFTSNKSVEIEVLVDADCVVDSSQKRYRAASVFTYVSLSQEGRSLPMPQLVPETQDEKGFEAWLGGSRL


[0733] Further analysis of the NOV78a protein yielded the following properties shown in Table 78B.
409TABLE 78BProtein Sequence Properties NOV78aPSort0.8000 probability located in microbody (peroxisome);analysis:0.1000 probability located in mitochondrial matrix space;0.1000 probability located in lysosome (lumen); 0.0000probability located in endoplasmic reticulum (membrane)SignalPNo Known Signal Sequence Predictedanalysis:


[0734] A search of the NOV78a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 78C.
410TABLE 78cGeneseq Results for NOV78aNOV78aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAW74896Human secreted protein encoded by 1 . . . 310273/313 (87%) e−154gene 169 clone HPTTU11-Homo 1 . . . 313292/313 (93%)sapiens, 339 aa. [WO9839448-A2,11 SEP. 1998]AAY71115Human Hydrolase protein-13 1 . . . 310247/313 (78%) e−133(HYDRL-13)-Homo sapiens, 375 33 . . . 316266/313 (84%)aa. [WO200028045-A2, 18 MAY 2000]AAY35275Chlamydia pneumoniae187 . . . 310 35/124 (28%)1e−09transmembrane protein sequence- 16 . . . 138 72/124 (57%)Chlamydia pneumoniae, 155 aa.[WO9927105-A2, 3 JUN. 1999]AAG92590C glutamicum protein fragment 24 . . . 309 69/296 (23%)7e−08SEQ ID NO: 6344- 35 . . . 307112/296 (37%)Corynebacterium glutamicum, 339aa. [EP1108790-A2, 20 JUN. 2001]AAB76624Corynebacterium glutamicum MCT 24 . . . 309 69/296 (23%)7e−08protein SEQ ID NO: 230- 35 . . . 307112/296 (37%)Corynebacterium glutamicum, 339aa. [WO200100805-A2, 4 JAN. 2001]


[0735] In a BLAST search of public sequence databases, the NOV78a protein was found to have homology to the proteins shown in the BLASTP data in Table 78D.
411TABLE 78DPublic BLASTP Results for NOV78aNOV78aIdentities/ProteinResidues/Similarities forAccessionMatchthe MatchedExpectNumberProtein/Organism/LengthResiduesPortionValueO00154Cytosolic acyl coenzyme A thioester1 . . . 310274/313 (87%)e−154hydrolase (EC 3.1.2.2) (Long chain1 . . . 313293/313 (93%)acyl-CoA thioester hydrolase) (CTE-II) (Brain acyl-CoA hydrolase)(BACH) - Homo sapiens (Human),338 aa.Q91V12ACYL-COA HYDROLASE1 . . . 310265/313 (84%)e−150(HYPOTHETICAL 37.6 KDA1 . . . 313287/313 (91%)PROTEIN) - Mus musculus (Mouse),338 aa.Q64559Cytosolic acyl coenzyme A thioester1 . . . 310263/313 (84%)e−149hydrolase (EC 3.1.2.2) (Long chain1 . . . 313286/313 (91%)acyl-CoA thioester hydrolase) (CTE-II) (Brain acyl-CoA hydrolase)(BACH) (ACT) (LACH1) (ACH1) -Rattus norvegicus (Rat), 338 aa.JC5416palmitoyl-CoA hydrolase (EC12 . . . 310 251/302 (83%)e−1423.1.2.2), hepatic - rat, 343 aa.17 . . . 318 276/302 (91%)Q9Y541DJ202O8.3.1 (HBACH (BRAIN1 . . . 202181/204 (88%)e−100ACYL-COA HYDROLASE (ACYL33 . . . 236 190/204 (92%)COENZYME A THIOESTERHYDROLASE, EC 3.1.2.2))(ISOFORM 1)) - Homo sapiens,(Human), 237 aa (fragment).


[0736] PFam analysis predicts that the NOV78a protein contains the domains shown in the Table 78E.
412TABLE 78EDomain Analysis of NOV78aIdentities/SimilaritiesNOV78a Matchfor the MatchedExpectPfam DomainRegionRegionValueAcyl-CoA_hydro:165 . . . 30546/147(31%)1.1e−47domain 1 of 1131/147(89%)


[0737] The NOV79 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 79A.
413TABLE 79ANOV79 Sequence AnalysisSEQ ID NO: 2234203 bpNOV79aAATGTGATGGGATCACTAGCATGTCTGCGGAGAGCGGCCCTGGGACGAGATTGAGAAACG59452-01 DNA SequenceTCTGCCAGTAATGGGGGATGGACTAGAAACTTCCCAAATGTCTACAACACAGGCCCAGGCCCAACCCCAGCCAGCCAACGCAGCCAGCACCAACCCCCCGCCCCCAGAGACCTCCAACCCTAACAAGCCCAAGAGGCAGACCAACCAACTGCAATACCTGCTCAGAGTGGTGCTCAAGACACTATGGAAACACCAGTTTGCATGGCCTTTCCAGCAGCCTGTGGATGCCGTCAAGCTGAACCTCCCTGATTACTATAAGATCATTAAAACGCCTATGGATATGGGAACAATAAAGAAGCGCTTGGAAAACAACTATTACTGGAATGCTCAGGAATGTATCCAGGACTTCAACACTATGTTTACAAATTGTTACATCTACAACAAGCCTGGAGATGACATAGTCTTAATGGCAGAAGCTCTGGAAAAGCTCTTCTTGCAAAAAATAAATGAGCTACCCACAGAAGAAACCGAGATCATGATAGTCCAGGCAAAAGGAAGAGGACGTGGGAGGAAAGAAACAGGTACAGCAAAACCTGGCGTTTCCACGGTACCAAACACAACTCAAGCATCGACTCCTCCGCAGACCCAGACCCCTCAGCCGAATCCTCCTCCTGTGCAGGCCACGCCTCACCCCTTCCCTGCCGTCACCCCGGACCTCATCGTCCAGACCCCTGTCATGACAGTGGTGCCTCCCCAGCCACTGCAGACGCCCCCGCCAGTGCCCCCCCAGCCACAACCCCCACCCGCTCCAGCTCCCCAGCCCGTACAGAGCCACCCACCCATCATCGCGGCCACCCCACAGCCTGTGAAGACAAAGAAGGGAGTGAAGAGGAAAGCAGACACCACCACCCCCACCACCATTGACCCCATTCACGAGCCACCCTCGCTGCCCCCGGAGCCCAAGACCACCAAGCTGGGCCAGCGGCGGGAGAGCAGCCGGCCTGTGAAACCTCCAAAGAAGGACGTGCCCGACTCTCAGCAGCACCCAGCACCAGAGAAGAGCAGCAAGGTCTCGGAGCAGCTCAAGTGCTGCAGCGGCATCCTCAAGGAGATGTTTGCCAAGAAGCACGCCGCCTACGCCTGGCCCTTCTACAAGCCTGTGGACGTGGAGGCACTGGGCCTACACGACTACTGTGACATCATCAAGCACCCCATGGACATGAGCACAATCAAGTCTAAACTGGAGGCCCGTGAGTACCGTGATGCTCAGGAGTTTGGTGCTGACGTCCGATTGATGTTCTCCAACTGCTATAAGTACAACCCTCCTGACCATGAGGTGGTGGCCATGGCCCGCAAGCTCCAGGATGTGTTCGAAATGCGCTTTGCCAAGATGCCGGACGAGCCTGAGGAGCCAGTGGTGGCCGTGTCCTCCCCGGCAGTGCCCCCTCCCACCAAGGTTGTGGCCCCGCCCTCATCCAGCGACAGCAGCAGCGATAGCTCCTCGGACAGTGACAGTTCGACTGATGACTCTGAGGAGGAGCGAGCCCAGCGGCTGGCTGAGCTCCAGGAGCAGCTCAAAGCCGTGCACGAGCAGCTTGCAGCCCTCTCTCAGCCCCAGCAGAACAAACCAAAGAAAAAGGAGAAAGACAAGAAGGAAAAGAAAAAAGAAAAGCACAAAAGGAAAGAGGAAGTGGAAGAGAATAAAAAAAGCAAAGCCAAGGAACCTCCTCCTAAAAAGACGAAGAAAAATAATAGCAGCAACAGCAATGTGAGCAAGAAGGAGCCAGCGCCCATGAAGAGCAAGCCCCCTCCCACGTATGAGTCGGAGGAAGAGGACAAGTGCAAGCCTATGTCCTATGAGGAGAAGCGGCAGCTCAGCTTGGACATCAACAAGCTCCCCGGCGAGAAGCTGGGCCGCGTGGTGCACATCATCCAGTCACGGGAGCCCTCCCTGAAGAATTCCAACCCCGACGAGATTGAAATCGACTTTGAGACCCTGAAGCCGTCCACACTGCGTGAGCTGGAGCGCTATGTCACCTCCTGTTTGCGGAAGAAAAGGAAACCTCAAGCTGAGAAAGTTGATGTGATTGCCGGCTCCTCCAAGATGAAGGGCTTCTCGTCCTCAGAGTCGGAGAGCTCCAGTGAGTCCAGCTCCTCTGACAGCGAAGACTCCGAAACAGAGATGGCTCCGAAGTCAAAAAAGAAGGGGCACCCCGGGAGGGAGCAGAAGCAGCACCATCATCACCACCATCAGCAGATGCAGCAGGCCCCGGCTCCTGTGCCCCAGCAGCCGCCCCCGCCTCCCCAGCAGCCCCCACCGCCTCCACCTCCGCAGCAGCAACAGCAGCCGCCACCCCCGCCTCCCCCACCCTCCATGCCGCAGCAGGCAGCCCCGGCGATGAAGTCCTCGCCCCCACCCTTCATTGCCACCCAGGTGCCCGTCCTGGAGCCCCAGCTCCCAGGCAGCGTCTTTGACCCCATCGGCCACTTCACCCAGCCCATCCTGCACCTGCCGCAGCCTGAGCTGCCCCCTCACCTGCCCCAGCCGCCTGAGCACAGCACTCCACCCCATCTCAACCAGCACGCAGTGGTCTCTCCTCCAGCTTTGCACAACGCACTACCCCAGCAGCCATCACGGCCCAGCAACCGAGCCGCTGCCCTGCCTCCCAAGCCCGCCCGGCCCCCAGCCGTGTCACCAGCCTTGACCCAAACACCCCTGCTCCCACAGCCCCCCATGGCCCAACCCCCCCAAGTGCTGCTGGAGGATGAAGAGCCACCTGCCCCACCCCTCACCTCCATGCAGATGCAGCTGTACCTGCAGCAGCTGCAGAAGGTGCAGCCCCCTACGCCGCTACTCCCTTCCGTGAAGGTGCAGTCCCAGCCCCCACCCCCCCTGCCGCCCCCACCCCACCCCTCTGTGCAGCAGCAGCTGCAGCAGCAGCCGCCACCACCCCCACCACCCCAGCCCCAGCCTCCACCCCAGCAGCAGCATCAGCCCCCTCCACGGCCCGTGCACTTGCAGCCCATGCAGTTTTCCACCCACATCCAACAGCCCCCGCCACCCCAGGGCCAGCAGCCCCCCCATCCGCCCCCAGGCCAGCAGCCACCCCCGCCGCAGCCTGCCAAGCCTCAGCAAGTCATCCAGCACCACCATTCACCCCGGCACCACAAGTCGGACCCCTACTCAACCGGTCACCTCCGCGAAGCCCCCTCCCCGCTTATGATACATTCCCCCCAGATGTCACAGTTCCAGAGCCTGACCCACCAGTCTCCACCCCAGCAAAACGTCCAGCCTAAGAAACAGGTAACTGGCAGGGCTGGGCCAAGTCCTGTGGGCCAGGGCCGGGGGTGCCTGCCCACCTCACCGGCCGCTGTGCCTGTGCCATCCCAGGAGCTGCGTGCTGCCTCCGTGGTCCAGCCCCAGCCCCTCGTGGTGGTGAAGGAGGAGAAGATCCACTCACCCATCATCCGCAGCGAGCCCTTCAGCCCCTCGCTGCGGCCGGAGCCCCCCAAGCACCCGGAGAGCATCAAGGCCCCCGTTTATGTTCCAGGGCCGGAAATGAAGCCTGTGGATGTCGGGAGGCCTGTGATCCGGCCCCCAGAGCAGAACGCACCGCCACCAGGGGCCCCTGACAAGGACAAACAGAAACAGGAGCCGAAGACTCCAGTTGCGCCCAAAAAGGACCTGAAAATCAAGAACATGGGCTCCTGGGCCAGCCTAGTGCAGAAGCATCCGACCACCCCCTCCTCCACAGCCAAGTCATCCAGCGACAGCTTCGAGCAGTTCCGCCGCGCCGCTCGGGAGAAAGAGGAGCGTGAGAAGGCCCTGAAGGCTCAGGCCGAGCACGCTGAGAAGGAGAAGGAGCGGCTGCGGCAGGAGCGCATGAGGAGCCGAGAGGACGAGGATGCGCTGGAGCAGGCCCGGCGGGCCCATGAGGAGGCACGTCGGCGCCAGGAGCAGCAGCAGCAGCAGCGCCAGGAGCAACAGCAGCAGCAGCAACAGCAAGCAGCTGCGGTGGCTGCCGCCGCCACCCCACAGGCCCAGAGCTCCCAGCCCCAGTCCATGCTGGACCAGCAGAGGGAGTTGGCCCGGAAGCGGGAGCAGGAGCGAAGACGCCGGGAAGCCATGGCAGCTACCATTGACATGAATTTCCAGAGTGATCTATTGTCAATATTTGAAGAAAATCTTTTCTGAGCGCACCTAGORF Start: ATG at 21ORF Stop: TGA at 4191SEQ ID NO: 2241390 aaMW at 154728.4 kDNOV79a,MSAESGPGTRLRNLPVMGDGLETSQMSTTQAQAQPQPANAASTNPPPPETSNPNKPKRCG59452-01 ProteinSequencesQTNQLQYLLRVVLKTLWKHQFAWPFQQPVDAVKLNLPDYYKIIKTPMDMGTIKKRLENNYYWNAQECIQDFNTMFTNCYIYNKPGDDIVLMAEALEKLFLQKINELPTEETEIMIVQAKGRGRGRKETGTAKPGVSTVPNTTQASTPPQTQTPQPNPPPVQATPHPFPAVTPDLIVQTPVMTVVPPQPLQTPPPVPPQPQPPPAPAPQPVQSHPPIIAATPQPVKTKKGVKRKADTTTPTTIDPIHEPPSLPPEPKTTKLGQRRESSRPVKPPKKDVPDSQQHPAPEKSSKVSEQLKCCSGILKEMFAKKHAAYAWPFYKPVDVEALGLHDYCDIIKHPMDMSTIKSKLEAREYRDAQEFGADVRLMFSNCYKYNPPDHEVVAMARKLQDVFEMRFAKMPDEPEEPVVAVSSPAVPPPTKVVAPPSSSDSSSDSSSDSDSSTDDSEEERAQRLAELQEQLKAVHEQLAALSQPQQNKPKKKEKDKKEKKKEKHKRKEEVEENKKSKAKEPPPKKTKKNNSSNSNVSKKEPAPMKSKPPPTYESEEEDKCKPMSYEEKRQLSLDINKLPGEKLGRVVHIIQSREPSLKNSNPDEIEIDFETLKPSTLRELERYVTSCLRKKRKPQAEKVDVIAGSSKMKGFSSSESESSSESSSSDSEDSETEMAPKSKKKGHPGREQKQHHHHHHQQMQQAPAPVPQQPPPPPQQPPPPPPPQQQQQPPPPPPPPSMPQQAAPAMKSSPPPFIATQVPVLEPQLPGSVFDPIGHFTQPILHLPQPELPPHLPQPPEHSTPPHLNQHAVVSPPALHNALPQQPSRPSNRAAALPPKPARPPAVSPALTQTPLLPQPPMAQPPQVLLEDEEPPAPPLTSMQMQLYLQQLQKVQPPTPLLPSVKVQSQPPPPLPPPPHPSVQQQLQQQPPPPPPPQPQPPPQQQHQPPPRPVHLQPMQFSTHIQQPPPPQGQQPPHPPPGQQPPPPQPAKPQQVIQHHHSPRHHKSDPYSTGHLREAPSPLMIHSPQMSQFQSLTHQSPPQQNVQPKKQVTGRAGPSPVGQGRGCLPTSPAAVPVPSQELRAASVVQPQPLVVVKEEKIHSPIIRSEPFSPSLRPEPPKHPESIKAPVYVPGPEMKPVDVGRPVIRPPEQNAPPPGAPDKDKQKQEPKTPVAPKKDLKIKNMGSWASLVQKHPTTPSSTAKSSSDSFEQFRRAAREKEEREKALKAQAEHAEKEKERLRQERMRSREDEDALEQARRAHEEARRRQEQQQQQRQEQQQQQQQQAAAVAAAATPQAQSSQPQSMLDQQRELARKREQERRRREAMAATIDMNFQSDLLSIFEENLF


[0738] Further analysis of the NOV79a protein yielded the following properties shown in Table 79B.
414TABLE 79BProtein Sequence Properties NOV79aPSort0.9800 probability located in nucleus; 0.3000 probabilityanalysis:located in microbody (peroxisome); 0.1000 probabilitylocated in mitochondrial matrix space; 0.1000 probabilitylocated in lysosome (lumen)SignalPNo Known Signal Sequence Predictedanalysis:


[0739] A search of the NOV79a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 79C.
415TABLE 79CGeneseq Results for NOV79aNOV79aIdentities/Residues/SimilaritiesGeneseqProtein/Organism/LengthMatchfor theExceptIdentifier[Patent #, Date]ResiduesMatched RegionValueAAY57898Human transmembrane protein 1 . . . 667667/667 (100%)0.0HTMPN-22 - Homo sapiens, 688 1 . . . 667667/667 (100%)aa. [WO9961471-A2, 2 DEC1999]AAY07027Breast cancer associated antigen44 . . . 724407/732 (55%)0.0precursor sequence - Homo13 . . . 708487/732 (65%)sapiens, 754 aa. [WO9904265-A2,28 JAN 1999]AAY07114WO9904265 Seq ID No: 685 -35 . . . 738357/761 (46%) e−170Homo sapiens, 947 aa. 4 . . . 686444/761 (57%)[WO9904265-A2, 28 JAN 1999]AAW81168Transcriptional regulatory factor35 . . . 738357/761 (46%) e−170RING3 - Homo sapiens, 947 aa. 4 . . . 686444/761 (57%)[WO9848015-A1, 29 OCT 1998]AAU16206Human novel secreted protein, Seq51 . . . 255118/206 (57%)2e−59ID 1159 - Homo sapiens, 235 aa. 1 . . . 203137/206 (66%)[WO200155322-A2, 2 AUG2001]


[0740] In a BLAST search of public sequence databases, the NOV79a protein was found to have homology to the proteins shown in the BLASTP data in Table 79D.
416TABLE 79DPublic BLASTP Results for NOV79aNOV79aIdentities/ProteinResidues/Similarities forAccessionMatchthe MatchedExpectNumberProtein/Organism/LengthResiduesPortionValueO60885Bromodomain-containing protein1 . . . 13901357/1391(97%)0.04 (HUNK1 protein) - Homo1 . . . 13621360/1391(97%)sapiens (Human), 1362 aa.Q9ESU6CELL PROLIFERATION1 . . . 13901318/1400(94%)0.0RELATED PROTEIN CAP -1 . . . 14001338/1400(95%)Mus musculus (Mouse), 1400 aa.AAL67833BROMODOMAIN-1 . . . 13901318/1400(94%)0.0CONTAINING PROTEIN BRD41 . . . 14001338/1400(95%)LONG VARIANT - Musmusculus (Mouse), 1400 aa.O60433R31546_1 - Homo sapiens1 . . . 719 719/719(100%)0.0(Human), 731 aa (fragment).12 . . . 730 719/719(100%)AAL67834BROMODOMAIN-1 . . . 719 694/720(96%)0.0CONTAINING PROTEIN BRD41 . . . 720 700/720(96%)SHORT VARIANT - Musmusculus (Mouse), 723 aa.


[0741] PFam analysis predicts that the NOV79a protein contains the domains shown in the Table 79E.
417TABLE 79EDomain Analysis of NOV79aIdentities/SimilaritiesNOV79a Matchfor the MatchedExpectPfam DomainRegionRegionValuebromodomain: 63 . . . 15242/92 (46%)8.6e−45domain 1 of 282/92 (89%)bromodomain:356 . . . 44540/92 (43%)  3e−40domain 2 of 281/92 (88%)



Example 80

[0742] The NOV80 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 80A.
418TABLE 80ANOV80 Sequence AnalysisSEQ ID NO: 2251776 bpNOV80a,TGGTTCGTTTATTCCTGGGGTTGTCATATCATGGCTTATAATGACACAGACAGAAACCCG59572-01 DNA SequenceAGACTGAGAAGCTCCTAAAAAGAGTACGAGAACTGGAGCAAGAGGTGCAAAGACTTAAAAAGGAACAGGCCAAAAATAAGGAGGACTCAAACATTAGAGAAAATTCAGCAGGAGCTGGAAAAACTAAGCGTGCATTTGATTTCAGTGCTCATGGCCGAAGACACGTAGCCCTAAGAATAGCCTATATGGGCTGGGGATACCAGGGCTTTGCTAGTCAGGAAAACACAAATAATACCATTGAAGAGAAACTGTTTGAAGCTCTAACCAAGACTCGACTAGTAGAAAGCAGACAGACATCCAACTATCACCGATGTGGGAGAACAGATAAAGGAGTTAGTGCCTTTGGACAGGTGATCTCACTTGACCTTCGCTCTCAGTTTCCAAGGGGCAGGGATTCCGAGGACTTTAATGTAAAAGAGGAGGCTAATGCTGCTGCTGAAGAGATCCGTTATACCCACATTCTCAATCGGGTACTCCCTCCAGACATCCGTATATTGGCCTGGGCCCCTGTAGAACCAAGCTTCAGTGCTAGGTTCAGCTGCCTTGAGCGGACTTACCGCTATTTTTTCCCTCGTGCTGATTTAGATATTGTAACCATGGATTATGCAGCTCAGAAGTATGTTGGCACCCATGATTTCAGGAACTTGTGTAAAATGGATGTAGCCAACGGTGTGATTAATTTTCAGAGGACTATTCTATCTGCTCAAGTACAGCTAGTGGGCCAGAGCCCAGGTGAGGGGAGATGGCAAGAACCTTTCCAGTTATGTCAGTTTGAAGTGACTGGCCAGGCATTCCTTTATCATCAAGTCCGATGTATGATGGCTATCCTCTTTCTGATTGGCCAAGGAATGGAGAAGCCAGAGATTATTGATGAGCTGCTGAATATAGAGAAAAATCCCCAAAAGCCTCAATATAGTATGGCTGTAGAATTTCCTCTAGTCTTATATGACTGTAAGTTTGAAAATGTCAAGTGGATCTATGACCAGGAGGCTCAGGAGTTCAATATTACCCACCTACAACAACTGTGGGCTAATCATGCTGTCAAAACTCACATGTTGTATAGTATGCTACAAGGACTGGACACTGTTCCAGTACCCTGTGGAATAGGACCAAAGATGGATGGAATGACAGAATGGGGAAATGTTAAGCCCTCTGTCATAAAGCAGACCAGTGCCTTTGTAGAAGGAGTGAAGATGCGCACATATAAGCCCCTCATGGACCGTCCTAAATGCCAAGGACTGGAATCCCGGATCCAGCATTTTGTACGTAGGGGACGAATTGAGCACCCACATTTATTCCATGAGGAAGAAACAAAAGCCAAAAGGGACTGTAATGACACACTAGAGGAAGAGAATACTAATTTGGAGACACCAACGAAGAGGGTCTGTGTTGACACAGAAATTAAAAGCATCATTTAACCATAGACAATTTGCCAGGATCTAGGAACCACCTAATGGTAGGTGGACAGAAAAGGAAAAAAAAAAAAATTTACTTGCAAGTACTAGGAATTCAGATGATCAGCTCTTAAAAAAAAAAAAAAAGCAAAAAGACTAAAGCCCTATTAAGGAAGTTATTGCTTTAATAAGAAATTTCAAATATTCTCTTATCCCGGTCCAAAAGGATTAAGCGATTAAAGAACGTAAAATGGAGATGTATTTACATACACCTGGAAACCTGTGCCTTGTATTCAAATTCATTAAAGCCTAATCCTGCAAGAAORF Start: ATG at 31ORF Stop: TAA at 1474SEQ ID NO:226481 aaMW at 55646.8kDNOV80a,MAYNDTDRNQTEKLLKRVRELEQEVQRLKKEQAKNKEDSNIRENSAGAGKTKRAFDFSCG59572-01 Protein SequenceAHGRRHVALRIAYMGWGYQGFASQENTNNTIEEKLFEALTKTRLVESRQTSNYHRCGRTDKGVSAFGQVISLDLRSQFPRGRDSEDFNVKEEANAAAEEIRYTHILNRVLPPDIRILAWAPVEPSFSARFSCLERTYRYFFPRADLDIVTMDYAAQKYVGTHDFRNLCKMDVANGVINFQRTILSAQVQLVGQSPGEGRWQEPFQLCQFEVTGQAFLYHQVRCMMAILFLIGQGMEKPEIIDELLNIEKNPQKPQYSMAVEFPLVLYDCKFENVKWIYDQEAQEFNITHLQQLWANHAVKTHMLYSMLQGLDTVPVPCGIGPKMDGMTEWGNVKPSVIKQTSAFVEGVKMRTYKPLMDRPKCQGLESRIQHFVRRGRIEHPHLFHEEETKAKRDCNDTLEEENTNLETPTKRVCVDTEIKSIISEQ ID NO:2271508 bpNOV80b,CATGGCTTATAATGACACAGACAGAAACCAGACTGAGAAGCTCCTAAAAAGAGTACGACG59572-02 DNA SequenceGAACTGGAGCAAGAGGTGCAAAGACTTAAAAAGGAACAGGCCAAAAATAAGGAGGACTCAAACATTAGAGAAAATTCAGCAGGAGCTGGAAAAACTAAGCGTGCATTTGATTTCAGTGCTCATGGCCGAAGACACGTAGCCCTAAGAATAGCCTATATGGGCTGGGGATACCAGGGCTTTGCTAGTCAGGAAAACACAAATAATACCATTGAAGAGAAACTGTTTGAAGCTCTAACCAAGACTCGACTAGTAGAAAGCAGACAGACATCCAACTATCACCGATGTGGGAGAACAGATAAAGGAGTTAGTGCCTTTGGACAGGTGATCTCACTTGACCTTCGCTCTCAGTTTCCAAGGGGCAGGGATTCCGAGGACTTTAATGTAAAAGAGGAGGCTAATGCTGCTGCTGAAGAGATCCGTTATACCCACATTCTCAATCGGGTACTCCCTCCAGACATCCGTATATTGGCCTGGGCCCCTGTAGAACCAAGCTTCAGTGCTAGGTTCAGCTGCCTTGAGCGGACTTACCGCTATTTTTTCCCTCGTGCTGATTTAGATATTGTAACCATGGATTATGCAGCTCAGAAGTATGTTGGCACCCATGATTTCAGGAACTTGTGTAAAATGGATGTAGCCAACGGTGTGATTAATTTTCAGAGGACTATTCTATCTGCTCAAGTACAGCTAGTGGGCCAGAGCCCAGGTGAGGGGAGATGGCAAGAACCTTTCCAGTTATGTCAGTTTGAAGTGACTGGCCAGGCATTCCTTTATCATCAAGTCCGATGTATGATGGCTATCCTCTTTCTGATTGGCCAAGGAATGGAGAAGCCAGAGATTATTGATGAGCTGCTGAATATAGAGAAAAATCCCCAAAAGCCTCAATATAGTATGGCTGTAGAATTTCCTCTAGTCTTATATGACTGTAAGTTTGAAAATGTCAAGTGGATCTATGACCAGGAGGCTCAGGAGTTCAATATTACCCACCTACAACAACTGTGGGCTAATCATGCTGTCAAAACTCACATGTTGTATAGTATGCTACAAGGACTGGACACTGTTCCAGTACCCTGTGGAATAGGACCAAAGATGGATGGAATGACAGAATGGGGAAATGTTAAGCCCTCTGTCATAAAGCAGACCAGTGCCTTTGTAGAAGGAGTGAAGATGCGCACATATAAGCCCCTCATGGACCGTCCTAAATGCCAAGGACTGGAATCCCGGATCCAGCATTTTGTACGTAGGGGACGAATTGAGCACCCACATTTATTCCATGAGGAAGAAACAAAAGCCAAAAGGGACTGTAATGACACACTAGAGGAAGAGAATACTAATTTGGAGACACCAACGAAGAGGGTCTGTGTTGACACAGAAATTAAAAGTATCATTTAACCATAGACAATTTGCCAGGATCTAGGAACCACCTAATGGTAGGTGGACAGAAAAGGAAAAAORF Start: ATG at 2ORF Stop: TAA at 1445SEQ ID NO: 228481 aaMW at 55646.8 kDNOV80b,MAYNDTDRNQTEKLLKRVRELEQEVQRLKKEQAKNKEDSNIRENSAGAGKTKRAFDFSCG59572-02 Protein SequenceAHGRRHVALRIAYMGWGYQGFASQENTNNTIEEKLFEALTKTRLVESRQTSNYHRCGRTDKGVSAFGQVISLDLRSQFPRGRDSEDFNVKEEANAAAEEIRYTHILNRVLPPDIRILAWAPVEPSFSARFSCLERTYRYFFPRADLDIVTMDYAAQKYVGTHDFRNLCKMDVANGVINFQRTILSAQVQLVGQSPGEGRWQEPFQLCQFEVTGQAFLYHQVRCMMAILFLIGQGMEKPEIIDELLNIEKNPQKPQYSMAVEFPLVLYDCKFENVKWIYDQEAQEFNITHLQQLWANHAVKTHMLYSMLQGLDTVPVPCGIGPKMDGMTEWGNVKPSVIKQTSAFVEGVKMRTYKPLMDRPKCQGLESRIQHFVRRGRIEHPHLFHEEETKAKRDCNDTLEEENTNLETPTKRVCVDTEIKSII


[0743] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 80B.
419TABLE 80BComparison of NOV80a against NOV80b.Identities/SimilaritiesProteinNOV80a Residues/for theSequenceMatch ResiduesMatched RegionNOV80b1 . . . 481459/481 (95%)1 . . . 481459/481 (95%)


[0744] Further analysis of the NOV80a protein yielded the following properties shown in Table 80C.
420TABLE 80CProtein Sequence Properties NOV80aPSort0.6500 probability located in cytoplasm; 0.1000 probabilityanalysis:located in mitochondrial matrix space; 0.1000 probabilitylocated in lysosome (lumen); 0.0142 probability locatedin microbody (peroxisome)SignalPNo Known Signal Sequence Predictedanalysis:


[0745] A search of the NOV80a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 80D.
421TABLE 80DGeneseq Results for NOV80aNOV80aIdentieies/Residues/SimilaritiesGeneseqProtein/Organism/LengthMatchfor theExpectIdentifier[Patent #, Date]ResiduesMatched RegionValueAAM79457Human protein SEQ ID NO 3103 -1 . . . 481478/481(99%)0.0Homo sapiens, 490 aa.10 . . . 490 480/481(99%)[WO200157190-A2, 9 AUG2001]AAM78473Human protein SEQ ID NO 1135 -1 . . . 481478/481(99%)0.0Homo sapiens, 481 aa.1 . . . 481480/481(99%)[WO200157190-A2, 9 AUG2001]AAG64907Human depressed growth rate209 . . . 431 223/223(100%) e−132protein DEG1 - Homo sapiens,1 . . . 223223/223(100%)248 aa. [CN1296014-A, 23 MAY2001]AAG02637Human secreted protein, SEQ ID361 . . . 456 96/96(100%)5e−53NO: 6718 - Homo sapiens, 96 aa.1 . . . 96 96/96(100%)[EP1033401-A2, 6 SEP 2000]AAB96592Putative P. abyssi pseudourydilate65 . . . 367 79/305(25%)4e−16synthase I - Pyrococcus abyssi,3 . . . 261140/305(45%)263 aa. [FR2792651-A1, 27 OCT2000]


[0746] In a BLAST search of public sequence databases, the NOV80a protein was found to have homology to the proteins shown in the BLASTP data in Table 80E.
422TABLE 80EPublic BLASTP Results for NOV80aNOV80aIdentities/ProteinResidues/Similarities forAccessionMatchthe MatchedExpectNumberProtein/Organism/LengthResiduesPortionValueQ9BZE2FKSG32 - Homo sapiens (Human),1 . . . 481481/481(100%)0.0481 aa.1 . . . 481481/481(100%)Q96J23HYPOTHETICAL 55.6 KDA1 . . . 481478/481(99%)0.0PROTEIN - Homo sapiens (Human),1 . . . 481480/481(99%)481 aa.Q96NB4CDNA FLJ31140 FIS, CLONE1 . . . 481478/481(99%)0.0IMR322001218, HIGHLY1 . . . 481479/481(99%)SIMILAR TO MUS MUSCULUSPSEUDOURIDINE SYNTHASE 3(PUS3) MRNA - Homo sapiens(Human), 481 aa.Q9JI38PSEUDOURIDINE SYNTHASE 3 -5 . . . 480407/479(84%)0.0Mus musculus (Mouse), 481 aa.4 . . . 480434/479(89%)Q9D0F72610020J05RIK PROTEIN - Mus5 . . . 314276/312(88%)e−158musculus (Mouse), 316 aa.4 . . . 315291/312(92%)


[0747] PFam analysis predicts that the NOV80a protein contains the domains shown in the Table 80F.
423TABLE 80FDomain Analysis of NOV80aIdentities/SimilaritiesNOV80a Matchfor the MatchedExpectPfam DomainRegionRegionValuePseudoU_synth_1:88 . . . 30770/249(28%)4.7e−57domain 1 of 1176/249(71%)



Example 81

[0748] The NOV81 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 81A.
424TABLE 81ANOV81 Sequence AnalysisSEQ ID NO: 2293080 bpNOV81a,TTCCAGCCGGCAGGATGGAGGACGAGGAAGGCCCTGAGTATGGCAAACCTGACTTTGTCG59522-01 DNA SequenceGCTTTTGGACCAAGTGACCATGGAGGACTTCATGAGGAACCTGCAGCTCAGGTTCGAGAAGGGCCGCATCTACACCTACATCGGTGAGGTGCTGGTGTCCGTGAACCCCTACCAGGAGCTGCCCCTGTATGGGCCTGAGGCCATCGCCAGGTACCAGGGCCGTGAGCTCTATGAGCGGCCACCCCATCTCTATGCTGTGGCCAACGCCGCCTACAAGGCAATGAAGCACCGGTCCAGGGACACCTGCATCGTCATCTCAGGGGAGAGTGGGGCAGGGAAGACAGAAGCCAGTAAGCACATCATGCAGTACATCGCTGCTGTCACCAATCCAAGCCAGAGGGCTGAGGTGGAGAGGGTCAAGGACGTGCTGCTCAAGTCCACCTGTGTGCTGGAGGCCTTTGGCAATGCCCGCACCAACCGCAATCACAACTCCAGCCGCTTTGGCAAGTACATGGACATCAACTTTGACTTCAAGGGGGACCCGATCGGAGGACACATCCACAGCTACCTACTGGAGAAGTCTCGGGTCCTCAAGCAGCACGTGGGTGAAAGAAACTTCCACGCCTTCTACCAATTGCTGAGAGGCAGTGAGGACAAGCAGCTGCATGAACTGCACTTGGAGAGAAACCCTGCTGTATACAATTTCACACACCAGGGAGCAGGACTCAACATGACTGTGAGTGATGAGCAGAGCCACCAGGCAGTGACCGAGGCCATGAGGGTCATCGGCTTCAGTCCTGAAGAGGTGGAGTCTGTGCATCGCATCCTGGCTGCCATATTGCACCTGGGAAACATCGAGTTTGTGGAGACGGAGGAGGGTGGGCTGCAGAAGGAGGGCCTGGCAGTGGCCGAGGAGGCACTGGTGGACCATGTGGCTGAGCTGACGGCCACACCCCGGGACCTCGTGCTCCGCTCCCTGCTGGCTCGCACAGTTGCCTCGGGAGGCAGGGAACTCATAGAGAAGGGCCACACTGCAGCTGAGGCCAGCTATGCCCGGGATGCCTGTGCCAAGGCAGTGTACCAGCGGCTGTTTGAGTGGGTGGTGAACAGGATCAACAGTGTCATGGAACCCCGGGGCCGGGATCCTCGGCGTGATGGCAAGGACACAGTCATTGGCGTGCTGGACATCTATGGCTTCGAGGTGTTTCCCGTCAACAGTTTCGAGCAGTTCTGCATCAACTACTGCAACGAGAAGCTGCAGCAGCTATTCATCCAGCTCATCCTGAAGCAGGAACAGGAAGAGTACGAGCGCGAGGGCATCACCTGGCAGAGCGTTGAGTATTTCAACAACGCCACCATTGTGGATCTGGTGGAGCGGCCCCACCGTGGCATCCTGGCCGTGCTGGACGAGGCCTGCAGCTCTGCTGGCACCATCACTGACCGAATCTTCCTGCAGACCCTGGACATGCACCACCGCCATCACCTACACTACACCAGCCGCCAGCTCTGCCCCACAGACAAGACCATGGAGTTTGGCCGAGACTTCCGGATCAAGCACTATGCAGGGGACGTCACGTACTCCGTGGAAGGCTTCATCGACAAGAACAGAGATTTCCTCTTCCAGGACTTCAAGCGGCTGCTGTACAACAGCACGGACCCCACTCTACGGGCCATGTGGCCGGACGGGCAGCAGGACATCACAGAGGTGACCAAGCGCCCCCTGACGGCTGGCACACTCTTCAAGAACTCCATGGTGGCCCTGGTGGAGAACCTTGCCTCCAAGGAGCCCTTCTACGTCCGCTGCATCAAGCCCAATGAGGACAAGGTAGCTGGGAAGCTGGATGAGAACCACTGTCGCCACCAGGTCGCATACCTGGGGCTGCTGGAGAATGTGAGGGTCCGCAGGGCTGGCTTCGCTTCCCGCCAGCCCTACTCTCGATTCCTGCTCAGGTACAAGATGACCTGTGAATACACATGGCCCAACCACCTGCTGGGCTCCGACAAGGCAGCCGTGAGCGCTCTCCTGGAGCAGCACGGGCTGCAGGGGGACGTGGCCTTTGGCCACAGCAAGCTGTTCATCCGCTCACCCCGGACACTGGTCACACTGGAGCAGAGCCGAGCCCGCCTCATCCCCATCATTGTGCTGCTATTGCAGAAGGCATGGCGGGGCACCTTGGCGAGGTGGCGCTGCCGGAGGCTGAGGGCTATCTACACCATCATGCGCTGGTTCCGGAGACACAAGGTGCGGGCTCACCTGGCTGAGCTGCAGCGGCGATTCCAGGCTGCAAGGCAGCCGCCACTCTACGGGCGTGACCTTGTGTGGCCGCTGCCCCCTGCTGTGCTGCAGCCCTTCCAGGACACCTGCCACGCACTCTTCTGCAGGTGGCGGGCCCGGCAGCTGGTGAAGAACATCCCCCCTTCAGACATGCCCCAGATCAAGGCCAAGGTGGCCGCCATGGGGGCCCTGCAAGGGCTTCGTCAGGACTGGGGCTGCCGACGGGCCTGGGCCCGAGACTACCTGTCCTCTGCCACTGACAATCCCACAGCATCAAGCCTGTTTGCTCAGCGACTAAAGACACTTCAGGACAAAGATGGCTTCGGGGCTGTGCTCTTTTCAAGCCATGTCCGCAAGGTGAACCGCTTCCACAAGATCCGGAACCGGGCCCTCCTGCTCACAGACCAGCACCTCTACAAGCTGGACCCTGACCGGCAGTACCGGGTGATGCGGGCCGTGCCCCTTGAGGCGGTGACGGGGCTGAGCGTGACCAGCGGAGGAGACCAGCTGGTGGTGCTGCACGCCCGCGGCCAGGACGACCTCGTGGTGTGCCTGCACCGCTCCCGGCCGCCATTGGACAACCGCGTTGGGGAGCTGGTGGGCGTGCTGGCCGCACACTGCCGCAGGGAGGGCCGCACCCTGGAGGTTCGCGTCTCCGACTGCATCCCACTAAGCCATCGCGGGGTCCGGCGCCTCATCTCCGTGGAGCCCAGGCCGGAGCAGCCAGAGCCCGATTTCCGCTGCGCTCGCGGCTCCTTCACCCTGCTCTGGCCCAGCCGCTGAGCGCCCGCACCCGCCGCACCCCGAORF Start: ATG at 15ORF Stop: TGA at 3054SEQ ID NO: 2301013 aaMW at 116044.5kDNOV81a,MEDEEGPEYGKPDFVLLDQVTMEDFMRNLQLRFEKGRIYTYIGEVLVSVNPYQELPLYCG59522-01 ProteinSequenceGPEAIARYQGRELYERPPHLYAVANAAYKAMKHRSRDTCIVISGESGAGKTEASKHIMQYIAAVTNPSQRAEVERVKDVLLKSTCVLEAFGNARTNRNHNSSRFGKYMDINFDFKGDPIGGHIHSYLLEKSRVLKQHVGERNFHAFYQLLRGSEDKQLHELHLERNPAVYNFTHQGAGLNMTVSDEQSHQAVTEAMRVIGFSPEEVESVHRILAAILHLGNIEFVETEEGGLQKEGLAVAEEALVDHVAELTATPRDLVLRSLLARTVASGGRELIEKGHTAAEASYARDACAKAVYQRLFEWVVNRINSVMEPRGRDPRRDGKDTVIGVLDIYGFEVFPVNSFEQFCINYCNEKLQQLFIQLILKQEQEEYEREGITWQSVEYFNNATIVDLVERPHRGILAVLDEACSSAGTITDRIFLQTLDMHHRHHLHYTSRQLCPTDKTMEFGRDFRIKHYAGDVTYSVEGFIDKNRDFLFQDFKRLLYNSTDPTLRAMWPDGQQDITEVTKRPLTAGTLFKNSMVALVENLASKEPFYVRCIKPNEDKVAGKLDENHCRHQVAYLGLLENVRVRRAGFASRQPYSRFLLRYKMTCEYTWPNHLLGSDKAAVSALLEQHGLQGDVAFGHSKLFIRSPRTLVTLEQSRARLIPIIVLLLQKAWRGTLARWRCRRLRAIYTIMRWFRRHKVRAHLAELQRRFQAARQPPLYGRDLVWPLPPAVLQPFQDTCHALFCRWRARQLVKNIPPSDMPQIKAKVAAMGALQGLRQDWGCRRAWARDYLSSATDNPTASSLFAQRLKTLQDKDGFGAVLFSSHVRKVNRFHKIRNRALLLTDQHLYKLDPDRQYRVMRAVPLEAVTGLSVTSGGDQLVVLHARGQDDLVVCLHRSRPPLDNRVGELVGVLAAHCRREGRTLEVRVSDCIPLSHRGVRRLISVEPRPEQPEPDFRCARGSFTLLWPSR


[0749] Further analysis of the NOV81a protein yielded the following properties shown in Table 81B.
425TABLE 81BProtein Sequence Properties NOV81aPSort0.8800 probability located in nucleus; 0.3902 probabilityanalysis:located in microbody (peroxisome); 0.2210 probabilitylocated in lysosome (lumen); 0.1000 probability locatedin mitochondrial matrix spaceSignalPNo Known Signal Sequence Predictedanalysis:


[0750] A search of the NOV81a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 81C.
426TABLE 81CGeneseq Results for NOV81aNOV81aIdentities/Residues/SimilaritiesGeneseqProtein/Organism/LengthMatchfor theExpectIdentifier[Patent #, Date]ResiduesMatched RegionValueAAU23125Novel human enzyme1 . . . 10131009/1018(99%)0.0polypeptide #211-Homo9 . . . 10261011/1018(99%)sapiens, 1026 aa.[WO200155301-A2, 2 AUG2001]AAU23128Novel human enzyme1 . . . 853851/858(99%)0.0polypeptide #214 - Homo9 . . . 866851/858(99%)sapiens, 909 aa. [WO200155301-A2, 2 AUG 2001]AAM80123Human protein SEQ ID NO 3769 -243 . . . 1011 438/769(56%)0.0Homo sapiens, 764 aa.1 . . . 762570/769(73%)[WO200157190-A2, 9 AUG2001]AAM79139Human protein SEQ ID NO 1801 -254 . . . 1011 434/758(57%)0.0Homo sapiens, 753 aa.1 . . . 751564/758(74%)[WO200157190-A2, 9 AUG2001]AAM39991Human polypeptide SEQ ID NO10 . . . 933 410/966(42%)0.03136 - Homo sapiens, 1063 aa.47 . . . 986 556/966(57%)[WO200153312-A1, 26 JUL2001]


[0751] In a BLAST search of public sequence databases, the NOV81a protein was found to have homology to the proteins shown in the BLASTP data in Table 81D.
427TABLE 81DPublic BLASTP Results for NOV81aNOV81aIdentities/ProteinResidues/Similarities forAccessionMatchthe MatchedExpectNumberProtein/Organism/LengthResiduesPortionValueQ63357MYOSIN I - Rattus norvegicus1 . . . 1011606/1011(59%)0.0(Rat), 1006 aa.1 . . . 1004780/1011(76%)A53933myosin I myr 4 - rat, 1006 aa.1 . . . 1011604/1011(59%)0.01 . . . 1004778/1011(76%)Q96RI6UNCONVENTIONAL MYOSIN33 . . . 646 612/619(98%)0.01G VALINE FORM - Homo1 . . . 619 612/619(98%)sapiens, (Human), 633 aa(fragment).Q96RI5UNCONVENTIONAL MYOSIN33 . . . 646 611/619(98%)0.01G METHONINE FORM - Homo1 . . . 619 612/619(98%)sapiens, (Human), 633 aa(fragment).Q23978Myosin IA (MIA) (Brush border8 . . . 1012503/1017(49%)0.0myosin IA) (BBMIA) - Drosophila6 . . . 1007686/1017(66%)melanogaster (Fruit fly), 1011 aa.


[0752] PFam analysis predicts that the NOV81a protein contains the domains shown in the Table 81E.
428TABLE 81EDomain Analysis of NOV81aIdentities/SimilaritiesNOV81a Matchfor the MatchedExpectPfam DomainRegionRegionValuePRK: domain 1 of 197 . . . 1098/13(62%)3.710/13(77%)Vir_DNA_binding:575 . . . 592 5/18(28%)8.2domain 1 of 114/18(78%)myosin_head:11 . . . 689305/747(41%)8.1e−288domain 1 of 1531/747(71%)



Example 82

[0753] The NOV82 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 82A.
429TABLE 82ANOV82 Sequence AnalysisSEQ ID NO: 2311066 bpNOV82a,GAACGAATGGGAAACCAGAAATCAGATATTTATGCCCAAGCAAAGCAGGATTTCGTTCCG59520-01 DNA SequenceAGCACTACTCCCAGATCGTTAGGGTGCTGACTGAGGATGAGATGGGGCACCCAGAGACAGGAGATGCTACTGCCCGGCTCAAGGAGGTCCTGGAGTACAATGCCATTGGAGGCAAGTATCACCGAGGTTTGATGGTGCTAGTAGCGTTCCGGGAGCTGGTGGAGCCGAGGAAACTGGATGCTGATAGTCTCCAGTGGGCACCGACTGTGGGCTGGTATGCGCAACTGCTGCAAGCTTTCTTCCTGGTGGCAGATGACATTATGGATTCATCCCTTACCTGCCAGGGACAGATCTCCTGGTATCAGAAGCTGGGCATGGGTTTGGATGCCATCAATGATGCTATCCTTCTGGAAGCATGTATCTACTGCCTGCTGAAGCTGTATTGCCGGGAGCAGCCCTATTACCTGAACCTGATGGAGCTCTTCCAGCAGAATTCTTATCAGACTGAGATTGGGCAGACCCTCGACCTCATCACAACCCCCCAGGGCAATGTGGATCTTCGCAGATGCACCGAAAAAAGGCACAAATCTGTTGTCAAGTACAAGACAGCTTTCTACTCCTTCTACCTTCCTGTAGCTGCAGCCATGTACATGTCAAGAATGGATGACAAGAAGGAGCACACCAGTGCCAAGAAGATCCTGCTGGAGATTCAAGAGTTCTTTCAGATTCAGGATGATTACCTTGACTTCTCTGGGGACCCCAGTGTGACTGGCAGAGTTGGCAATGACTTCCAGGACAACAAATGCAGCTGGCTGGTGGTTCAGTGTCTGCTACAGGCCACTCCAGAACAGTACCAGATCCTGAAGGAAAATTACAGGCAGAAGGAGGCCGAGAAGGTGGCCCGGGTGAAGGCACTATACGAGGAGCTGGATCTGCCAGCCGTGTTCTTGCAGTATGAGAAAGACAGTTACAGCCACGTTATGGGTCTCATCGAACAGTACGCAGAGCCCCTGCCCCCAGCCATCTTTCTGGGGCTTGTGCACAAAATCTACAAGTGGAAAAAGTGACORF Start: ATG at 7ORF Stop: TGA at 1063SEQ ID NO: 232352 aa MW at 40740.3 kDNOV82a,MGNQKSDIYAQAKQDFVQHYSQIVRVLTEDEMGHPETGDATARLKEVLEYNAIGGKYHCG59520-01 Protein SequenceRGLMVLVAFRELVEPRKLDADSLQWAPTVGWYAQLLQAFFLVADDIMDSSLTCQGQISWYQKLGMGLDAINDAILLEACIYCLLKLYCREQPYYLNLMELFQQNSYQTEIGQTLDLITTPQGNVDLRRCTEKRHKSVVKYKTAFYSFYLPVAAAMYMSRMDDKKEHTSAKKILLEIQEFFQIQDDYLDFSGDPSVTGRVGNDFQDNKCSWLVVQCLLQATPEQYQILKENYRQKEAEKVARVKALYEELDLPAVFLQYEKDSYSHVMGLIEQYAEPLPPAIFLGLVHKIYKWKK


[0754] Further analysis of the NOV82a protein yielded the following properties shown in Table 82B.
430TABLE 82BProtein Sequence Properties NOV82aPSort0.4066 probability located in microbody (peroxisome); 0.3000analysis:probability located in nucleus; 0.1000 probability located inmitochondrial matrix space; 0.1000 probability located inlysosome (lumen)SignalPNo Known Signal Sequence Predictedanalysis:


[0755] A search of the NOV82a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 82C.
431TABLE 82CGeneseq Results for NOV82aNOV82aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAG29733Arabidopsis thaliana protein10 . . . 352147/343 (42%)7e−75fragment SEQ ID NO: 35427- 2 . . . 342219/343 (62%)Arabidopsis thaliana, 342 aa.[EP1033405-A2, 6 SEP. 2000]AAG29732Arabidopsis thaliana protein10 . . . 352147/343 (42%)7e−75fragment SEQ ID NO: 35426- 9 . . . 349219/343 (62%)Arabidopsis thaliana, 349 aa.[EP1033405-A2, 6 SEP. 2000]AAG29734Arabidopsis thaliana protein47 . . . 352138/306 (45%)4e−73fragment SEQ ID NO: 35428- 1 . . . 305204/306 (66%)Arabidopsis thaliana, 305 aa.[EP1033405-A2, 6 SEP. 2000]AAY43635Amino acid sequence of the farnesyl12 . . . 352145/346 (41%)4e−69pyrophosphate synthase enzyme−11 . . . 355208/346 (59%)Phaffia rhodozyma, 355 aa.[EP955363-A2, 10 NOV. 1999]AAB48971Sunflower seedling farnesyl13 . . . 352138/343 (40%)3e−64pyrophosphate synthase (FPS)- 6 . . . 341204/343 (59%)Helianthus annuus, 341 aa.[EP1063297-A1, 27 DEC. 2000]


[0756] In a BLAST search of public sequence databases, the NOV82a protein was found to have homology to the proteins shown in the BLASTP data in Table 82D.
432TABLE 82DPublic BLASTP Results for NOV82aNOV82aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueQ96G29FARNESYL DIPHOSPHATE 2 . . . 352291/351 (82%)e−168SYNTHASE (FARNESYL69 . . . 419317/351 (89%)PYROPHOSPHATESYNTHETASE,DIMETHYLALLYLTRANSTRANSFERASE,GERANYLTRANSTRANSFERASE)-Homo sapiens (Human), 419 aa.P14324Farnesyl pyrophosphate synthetase 2 . . . 352291/351 (82%)e−168(FPP synthetase) (FPS) (Farnesyl 3 . . . 353317/351 (89%)diphosphate synthetase) [Includes:Dimethylallyltransferase (EC2.5.1.1); Geranyltranstransferase(EC 2.5.1.10)]-Homo sapiens(Human), 353 aa.A35726farnesyl-pyrophosphate synthetase- 2 . . . 352290/351 (82%)e−168human, 353 aa. 3 . . . 353316/351 (89%)AAL58886FARNESYL DIPHOSPHATE 2 . . . 352270/351 (76%)e−157SYNTHASE-Bos taurus (Bovine), 3 . . . 353308/351 (86%)353 aa.Q14329FARNESYL PYROPHOSPHATE 6 . . . 352268/347 (77%)e−150SYNTHETASE LIKE-4 PROTEIN- 2 . . . 348295/347 (84%)Homo sapiens (Human), 348 aa.


[0757] PFam analysis predicts that the NOV82a protein contains the domains shown in the Table 82E.
433TABLE 82EDomain Analysis of NOV82aIdentities/PfamNOV82aSimilarities forExpectDomainMatch Regionthe Matched RegionValuepolyprenyl_synt:43 . . . 315 82/285 (29%)6.3e−91domain 1 of 1237/285 (83%)



Example 83

[0758] The NOV83 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 83A.
434TABLE 83ANOV83 Sequence AnalysisSEQ ID NO: 233411 bpNOV83a,TGCCTACCCCGAGACTGCTGCTGTTCGGAGACCTGCAGGTGAATGCCCCATCACCATGCG59758-01 DNA SequenceTCTGACCTGGAGGCAAAACCTTCAACTGAGCATTTGGGGGATAAGATAAAAGATGAAGATATTAAACTCAGGGTTATTGGACAGGATAGCAGTGAGATTCATTTCAAAGTGAAAATGACAACACCTCTCAAGAAACTCAAGAAATCGTACTGTCAGAGACAGGGCGTTCCAGTGAATTCCCTCAGGTTTCTCTTTGAAGGTCAGAGAATTGCTGATAATCATACTCCAGAAGAACTGGGAATGGAGGAAGAAGATGTGATTGAGGTTTATCAGGAACAAATCGGAGGTCATTCAACAGTTTAGACATTCTTTTTTTTTTTCCTTTTCCCTCAATCCTTTTTTATTTTTTTAAAORF Start: ATG at 56ORF Stop: TAG at 359SEQ ID NO: 234101 aaMW at 11526.0 kDNOV83a,MSDLEAKPSTEHLGDKIKDEDIKLRVIGQDSSEIHFKVKMTTPLKKLKKSYCQRQGVPCG59758-01 Protein SequenceVNSLRFLFEGQRIADNHTPEELGMEEEDVIEVYQEQIGGHSTVSEQ ID NO: 235658 bpNOV83b,CTACCCCGAGACTGCTGCTGTTCGGAGACCTGCAGGTGAATGCCCCATCACCAATGTCTCG59758-02 DNA SequenceGACCTGGAGGCAAAACCTTCAACTGAGCATTTGGGGGATAAGATAAAAGATGAAGATATTAAACTCAGGGTTATTGGACAGGATAGCAGTGAGATTCATTTCAAAGTGAAAATGACAACACCTCTCAAGAAACTCAAGAAATCGTACTGTCAGAGACAGGGCGTTCCAGTGAATTCCCTCAGGTTTCTCTTTGAAGGTCAGAGAATTGCTGATAATCATACTCCAGAAGAACTGGGAATGGAGGAAGAAGATGTGATTGAGGTTTATCAGGAACAAATCGGAGGTCATTCAACAGTTTAGACAATCGGAGGTCATTCAACAGTTTAGACAATCGGAGGTCATTCAACAGTTTAGACAATCGGAGGTCATTCAACAGTTTAGACAATCGGAGGTCATTCAACAGTTTAGACAATCGGAGGTCATTCAACAGTTTAGACAATCGGAGGTCATTCAACAGTTTAGACAATCGGAGGTCATTCAACAGTTTAGACAATCGGAGGTCATTCAACAGTTTAGACAATCGGAGGTCATTCAACAGTTTAGACAATCGGAGGTCATTCAACAGTTTAGACAATCGGAGGTCATTCAACAGTTTAGACAORF Start: ATG at 53ORF Stop: TAG at 356SEQ ID NO: 236101 aaMW at 11526.0 kDNOV83b,MSDLEAKPSTEHLGDKIKDEDIKLRVIGQDSSEIHFKVKMTTPLKKLKKSYCQRQGVPCG59758-02 Protein SequenceVNSLRFLFEGQRIADNHTPEELGMEEEDVIEVYQEQIGGHSTV


[0759] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 83B.
435TABLE 83BComparison of NOV83a against NOV83b.Identities/ProteinNOV83a Residues/Similarities forSequenceMatch Residuesthe Matched RegionNOV83b1 . . . 101101/101 (100%)1 . . . 101101/101 (100%)


[0760] Further analysis of the NOV83a protein yielded the following properties shown in Table 83C.
436TABLE 83CProtein Sequence Properties NOV83aPSort0.6500 probability located in cytoplasm; 0.1000 probabilityanalysis:located in mitochondrial matrix space; 0.1000 probabilitylocated in lysosome (lumen); 0.0000 probability located inendoplasmic reticulum (membrane)SignalPNo Known Signal Sequence Predictedanalysis:


[0761] A search of the NOV83a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 83D.
437TABLE 83DGeneseq Results for NOV83aNOV83aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAM79976Human protein SEQ ID NO 3622- 1 . . . 101100/101 (99%)1e−52Homo sapiens, 125 aa.25 . . . 125100/101 (99%)[WO200157190-A2, 9 AUG. 2001]AAM78992Human protein SEQ ID NO 1654- 1 . . . 101100/101 (99%)1e−52Homo sapiens, 101 aa. 1 . . . 101100/101 (99%)[WO200157190-A2, 9 AUG. 2001]AAY49967Human sentrin protein sequence- 1 . . . 101 89/101 (88%)2e−45Homo sapiens, 101 aa. 1 . . . 101 94/101 (92%)[U.S. Pat. No. 5985664-A,16 NOV. 1999]AAW87984Ubiquitin-like domain of the 1 . . . 101 89/101 (88%)2e−45protein SUMO1-Mammalia, 101 1 . . . 101 94/101 (92%)aa. [WO9857978-A1, 23 DEC. 1998]AAW60079Homo sapiens sentrin-1 1 . . . 101 89/101 (88%)2e−45polypeptide-Homo sapiens, 101 1 . . . 101 94/101 (92%)aa. [WO9820038-A1, 14 MAY 1998]


[0762] In a BLAST search of public sequence databases, the NOV83a protein was found to have homology to the proteins shown in the BLASTP data in Table 83E.
438TABLE 83EPublic BLASTP Results for NOV83aNOV83aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueQ93068Ubiquitin-like protein SMT3C1 . . . 10189/101 (88%)6e−45precursor (Ubiquitin-homology domain1 . . . 10194/101 (92%)protein PIC1) (Ubiquitin-like proteinUBL1) (Ubiquitin-related proteinSUMO-1) (GAP modifying protein 1)(GMP1) (Sentrin)-Homo sapiens(Human), and, 101 aa.Q9MZD5SENTRIN-Cervus nippon (Sika deer),1 . . . 10188/101 (87%)2e−44101 aa.1 . . . 10193/101 (91%)O57686SUMO-1 PROTEIN-Xenopus laevis1 . . . 10083/101 (82%)2e−39(African clawed frog), 102 aa.1 . . . 10190/101 (88%)Q9PT08SMALL UBIQUITIN-RELATED1 . . . 9772/97 (74%)9e−35PROTEIN 1-Oncorhynchus mykiss1 . . . 9784/97 (86%)(Rainbow trout) (Salmo gairdneri), 101aa.Q9D4664933411G06RIK PROTEIN-Mus1 . . . 9768/97 (70%)8e−30musculus (Mouse), 117 aa.1 . . . 9680/97 (82%)


[0763] PFam analysis predicts that the NOV83a protein contains the domains shown in the Table 83F.
439TABLE 83FDomain Analysis of NOV83aIdentities/PfamNOV83aSimilarities forExpectDomainMatch Regionthe Matched RegionValueubiquitin:20 . . . 9514/83 (17%)4.7e−18domain 1 of 166/83 (80%)



Example 84

[0764] The NOV84 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 84A.
440TABLE 84ANOV84 Sequence AnalysisSEQ ID NO: 237912 bpNOV84a,ACTCACTAATGGGCTCGAGCGGCTGCCTGTGTTTCAGCGGCTCGGGGAAATCCACCGTCG59586-01 DNA SequenceGGGCGCCCTGCTGGCATCTGAGCTGGGATGGAAATTCTATGATGCTGATGATTATCACCCGGAGGAAAATCGAAGGAAGATGGGAAAAGGCATACCGCTCAATGACCAGGACCGGATTCCATGGCTCTGTAACTTGCATGACATTTTACTAAGAGATGTAGCCTCGGGACAGCGTGTGGTTCTAGCCTGTTCAGCCCTGAAGAAAACGTACAGAGACATATTAACACAAGGAAAAGATGGTGTAGCTCTGAAGTGTGAGGAGTCGGGAAAGGAAGCAAAGCAGGCTGAGATGCAGCTCCTGGTGGTCCATCTGAGCGGGTCGTTTGAGGTCATCTCTGGACGCTTACTCAAAAGAGAGGGACATTTTATGCCCCCTGAATTATTGCAGTCCCAGTTTGAGACTCTGGAGCCCCCAGCAGCTCCAGAAAACTTTATCCAAATAAGTGTGGACAAAAATGTTTCAGAGATAATTGCTACAATTATGGAAACCCTAAAAATGAAATGACAATGATTTTGTATCAGTGGTCCAAACAGAACTAAGCATAAATCATTGTGCCATCCCAAACCTCGTTCCAGCCGCCTTGCCCATACTAGATTCTAAATGTTTCTAAAGGCAAACCCCAATGTGTCAAGACAGACTTGTTTAGGTGTAATTTTAGGAATTATGCTGGTTCATCAGGAAGCAGAGGGGGAGTTTTAAAAGTCAAGCTTAAATTGAAGTTTAAATTCATCTATAACCAAATCAAATGATCAGAGGAAATTCTGTAATCAATGCTGGAAATCGTTACATTGTTTAGAACATTCTTGCTCATGCCTGTATTTGCACAAATAAATGAAACTTCGCTGTAAAAAAAORF Start: ATG at 9ORF Stop: TGA at 561SEQ ID NO: 238184 aaMW at 20352.2 kDNOV84a,MGSSGCLCFSGSGKSTVGALLASELGWKFYDADDYHPEENRRKMGKGIPLNDQDRIPWCG59586-01 Protein SequenceLCNLHDILLRDVASGQRVVLACSALKKTYRDILTQGKDGVALKCEESGKEAKQAEMQLLVVHLSGSFEVISGRLLKREGHFMPPELLQSQFETLEPPAAPENFIQISVDKNVSEIIATIMETLKMK


[0765] Further analysis of the NOV84a protein yielded the following properties shown in Table 84B.
441TABLE 84BProtein Sequence Properties NOV84aPSort0.6500 probability located in cytoplasm; 0.1000 probabilityanalysis:located in mitochondrial matrix space; 0.1000 probabilitylocated in lysosome (lumen); 0.1000 probability located inplasma membraneSignalPNo Known Signal Sequence Predictedanalysis:


[0766] A search of the NOV84a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 84C.
442TABLE 84CGeneseq Results for NOV84aNOV84aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAG73989Human colon cancer antigen10 . . . 184175/175 (100%)1e−97protein SEQ ID NO: 4753-Homo19 . . . 193175/175 (100%)sapiens, 193 aa. [WO200122920-A2, 5 APR. 2001]AAB58998Breast and ovarian cancer10 . . . 184175/175 (100%)1e−97associated antigen protein sequence19 . . . 193175/175 (100%)SEQ ID 706-Homo sapiens, 193aa. [WO200055173-A1,21 SEP. 2000]AAM89100Human immune/haematopoietic24 . . . 126 70/103 (67%)1e−34antigen SEQ ID NO: 16693-Homo22 . . . 124 77/103 (73%)sapiens, 133 aa. [WO200157182-A2, 9 AUG. 2001]AAG50675Arabidopsis thaliana protein10 . . . 179 75/173 (43%)4e−28fragment SEQ ID NO: 64243- 4 . . . 167102/173 (58%)Arabidopsis thaliana, 175 aa.[EP1033405-A2, 6 SEP. 2000]AAG50674Arabidopsis thaliana protein10 . . . 179 75/173 (43%)4e−28fragment SEQ ID NO: 64242-16 . . . 179102/173 (58%)Arabidopsis thaliana, 187 aa.[EP1033405-A2, 6 SEP. 2000]


[0767] In a BLAST search of public sequence databases, the NOV84a protein was found to have homology to the proteins shown in the BLASTP data in Table 84D.
443TABLE 84DPublic BLASTP Results for NOV84aNOV84aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueBAB74785GLUCONOKINASE-Anabaena10 . . . 183 72/174 (41%)1e−30sp. (strain PCC 7120), 160 aa. 9 . . . 160101/174 (57%)Q9RT56THERMORESISTANT10 . . . 183 66/174 (37%)1e−29GLUCONOKINASE- 4 . . . 159101/174 (57%)Deinococcus radiodurans, 172 aa.CAC93415PUTATIVE GLUCONOKINASE10 . . . 174 68/166 (40%)2e−29(EC 2.7.1.12)-Yersinia pestis,12 . . . 159 95/166 (56%)167 aa.Q9CMM6GLK-Pasteurella multocida, 17210 . . . 182 68/174 (39%)2e−29aa.15 . . . 169 99/174 (56%)AAK86014AGR_C_329P-Agrobacterium10 . . . 182 74/173 (42%)6e−29tumefaciens str. C58 (Cereon), 5 . . . 159 98/173 (55%)163 aa.


[0768] PFam analysis predicts that the NOV84a protein contains the domains shown in the Table 84E.
444TABLE 84EDomain Analysis of NOV84aIdentities/PfamNOV84aSimilarities forExpectDomainMatch Regionthe Matched RegionValueSKI: domain 1 of 19 . . . 182 37/206 (18%)1.1114/206 (55%)



Example 85

[0769] The NOV85 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 85A.
445TABLE 85ANOV85 Sequence AnalysisSEQ ID NO: 2394332 bpNOV85a,GGCGTATTAACGCGCGGGTGCACACCCCCACGGGCGCGCAATGAACAACTATGTGCTTCG59704-01 DNA SequenceAATGACGAGATCGGCCAGGGTGCCTTCAGCACTATTTACAAGGGCCGCTATCGCACCACCACCGAGTTCTACGCGATTGCTTCCATCGACAAGAAGCGACGGGAGCGCGTCGTGAACTGCGTTCAGCTGTTACGCTCCATGCACCACTCAAACGTCATAGAGTTCCACAACTGGTATGAGACCAACAATCACTTGTGGATCATTACGGAGTACTGCACCGGCGGAGACATGAGCACGATCCTCCGCTCGAACATTAATCTCACCACTCAGGCGGTCCAGGCGTTCGGCCGTGATGTGGCGATGGGCCTCATGTACATCCACAGTAAGGGTGTCGTGTATAACGACTTGCAGACTCGCAATCTGCTGATGGACTCCGCAGCAATGCTGCGCTTCCACGACTTTAGCTTGGCCTGTCTCTTCCAAGACGCGGCGACGCGGCCACTGGTGGGGACGCCACTGTACATGGCCCCCGAGTTGTTCATGGCGGATCGCCCGCTGTACTCGATGGCATCAGACCTGTGGTCCTTCGGTTGTGTGCTGCACGAGCTGGCGACAGGCAAGCCGCCCTTTGCCGCATCCGACCTCGAGACGCTGCTGGGCGACATACTGACGAGTCCGACGCCAGCGGTGCCTGGTGCGCCGGAGTCCTTTCAAACGCTCCTGTGCGGCCTGCTGGAAAAGGACCCGTTGAAGCGCTACGCGTGGGTCGATGTTGTCCGCAGCGAGTTCTGGGATGAGCCCTTGCCGCTGCCGAGCAACGGCTTTCCATCTCAGGTGGCGTGGGAGGACTACAAGCGTTCGCGTTCTGGACGCGGTGCGAGTCAGTATAATTGGACGGACTCCGATGTGCGTGTGGCAGTGGCTCACGCCGTGGGGGCAGCGAAATCAAACGCTTCTACGCACAACGTGGAGGAGAGGGAGCGAGCGGCTGCGACGTTGAACGTCGCGAAGGAGCTGGACTTCACTGCAAGCGCGGCGATGTTGCTGGAACGGTTACCGGAGCGGACACAGGAGCGTGCTGCGCACGCAACAGGCCATGTCGCGACCGCGCACGGCAGCCTGGTGCACGGCTGCCCATCCACGGCCTCAGCGGCGACCTCGCCAAGACGTTCAAGGACAAGGCGGCGCTGCTCAAGATTGTGGAAGAGGTCAAAACCGCTGTCGAGGGCTTCAAGCCGTGGGTGTCCTTCCACGTCGCTGCGCCACCCGGGCATGAGGGAGCGCCACTGGACCGGCTTGTCTCAGAAGCTCGGGATGAAGCTGGTGCCTGGCGACACACTGATGCTTCTGGAGGACTGCGAACCGCTGCTAGCGCACCGCGACACCATTATCAGCTACTGCGAGGTGGCCGCGAAGGAGTCGCAGATCGAGATGACGCTCAAGGACATGCGTGCCAAGTGGGAGACCAAGTGCTTCATCATCGAGGCATACAAGGAGACAGGCACGTACATCCTCAAGGACACCTCCGAGGTGGTGGAGCTCCTCGACGAGCACCTCAACGTCGTCCAGCAGCTGCAGTTCTCTCCATTCAAGGGCTACTTCGAGGAGTCCATCACGGACTGGGAGCGCTCCCTCAACCTCATCTCCGACATACTCGAACAATGGCTGGAGTGCCAGCGAGCGTGGCGTTATCTGGAGCCGATCCTCAACTCGGAGGACATCGCCATGCAGCTACCGCGACTGTCCACGCTGTTCGAGAAGGTGGACCGCACATGGAGACGTGTCATGGGCAACGCGCACGCGCAGCCAAACGCACTCGAGTACTGCATTGGCACAAACAAGCTCTTGGACCACCTGCGCGAGGCGAACCGGCTCCTCGAAGTGCTGCAGCACTTGATGGCGCAGAAGGTCAACGTTGCCGCTGTTGGTCCGACTGGCACCGGCAAGTCCATCTCACTCGCGCGTCTCGTGCTTGGCGGCGGCATGCCGGCCAACTTTCTTGGCCTCAACTTCACCTTCTCGGCGCAGACAAAGTGCACAGTGTTGCAGAATTCACTGATGGCCAAGTTCGATAAGCGGCGCTCGCACGTCTACGGCGCCCCTGCCGGTAAGCACTTTCTCATCTTCATTGACGACGCGAACCTGCCGCAGCCAGAGAAGTACGGCGCGCAGCCCCCGGTGGAGCTTCTGCGGCAGATGCTCGCCCAAGGCGGCTTCTACAACTTTACAGGTGGCATCAAGTGGTCCTCCATCATCGACTGCTCGCTTGCGCTGGCGATGGGGCCGCCTGGCGGGGGCCGCAGCCGGGTTTCGAACCGCTTTATGCGCTACTTCAATTACCTTGCCTTCCCCGAGATGTCGGACATGTCGAAGCGAACGATCTTGCAGGCCATCCTCGTCGGCGGCCTCGCGCAGAGCGGCCTCGCTGACCGCCTCGCGAACGTCGCCTCCGCCGTGGTCGATAGCACGTTGCGGGTGTTTCGCAAGTGCACCCAGGTCTTTCTGCCGACCCCGGCGCACGTGCACTACTCCTTCAACATGCGGGATGTGATGCGTGTTTTTCCCCTCTTGTACACAGCAGACAAGTCGGTGCTGCAGTCGGAGGAATCCATCGTGCGGCTGTGGATGCACGAGATGCAGCGCGTCTTCTACGATCGCCTCGTCGACGCGACAGACAAGGGTCTGTTCATCGAGTACCTCAATGCCGAGCTGCCGTCCATGGGGGTGGACAAGTCCTACAACGAGGTAGTGAAGGCTGACCGCCTCATCTTTGCCGACGTACTGAGCGACAAGGGCGTGTACGAGCAGATTACCGACATGAACGCCCTCACGACACGCATGAATGAGCTGCTGGAGGCGTACAATGACGAGAATGAAGTGAAGATGAACCTCGTGCTCTTCCTCGACGCCATCGAGCATGTCTGCCGTATCTCGCGCGTGCTGCGACTGCCGAACGGGCACTGCCTCCTCCTCGGCGTTGGCGGGTCGGGACGCAAGTCACTCACGCGCCTGGCTTGTTCTCTGATTGCCGAGATGGAGGTGTTCACGATTGAGCTGTCGAAGAACTTCGGTGTCAAGGAATGGCACGAGAGCCTCGCGAAGTTGCTGCTCGAGTGTGGCAAGGACGAGAAGAAGCGGACGTTTCTCTTCGCCGACACCCAGCTGGCGCATCCGACGTTTCTGGAGGATGTGGCGGGCCTGCTCACATCGGGTGATGTGCCGAACCTCTTTGAGGACCAAGATATCGAGCTCATCAACGACAAGTTTCGCGGCGTCTGCCTAAGCGAGAACCTGCCAACGACGAAGGTGTCGGTGTACGCGCGCTTTGTGAAGGAGGCGCGAGCCAACCTGCACCTTGTGCTCGCCTTCTCTCCCATCGGAGAGGCGTTTCGCAGCCGCCTGCGTATGTTCCCATCGCTCATTGCGTGCTGCACAATCGACTGGTTTGCTGAGTGGCCATCCGAGGCGCTACTGTCGGTAGCCGCAGTGCAGCTGAACGCCGGCGACGTTACTGACGTCATGGGGGCGGCAAGCCATGCCGACTTGCCGGGCTGCTTCCAGGCAGTGCACCGCGCGGCGGCGGAGGTGACGGAGCGCTTCTTCACGGAAACGCGTCGTCGCTCGTACGTGACGCCGACGTCCTATCTGTCGCTCCTCTCCAACTTCAAAGTGATGGCGGCGGCAAAACGCCGCTTCGTTCGCGAGCAGCGCGGCCGCCTCGAGAAGGGGCTGGAGAAGCTGCGGCACACCGAGGTGCAAGTGGCGGAGCTGGAGGCCCAGCTCAAGGCGCAGCAGCCGGTTCTGGTGCAGAAAAAGGCAGAGATTCAGTCGATGATGGAGCGGCTGACGGTGGACCGAAAGGAGGCGGCGGTGAAGGAGGCGGACGCGCGCAGGGAGGCCCAGCTTCCCGGTGGCCGTGCTGCATACGGCGGTGAAGATGACGAATGAGCCGCCGATGGGGCTGCGGGCGAACGTGATGCGCTCCTACTACGGCTTCACTCCCGAGGACCTCGAGCAGGAGGAGAAGCCCGCCGAGTTCAAAAAGATGTTGATGGCATCCGCATGCCTGGTCCCATACCCGAGCACTGAAGAGCAGGGTCTCTGGAGCCTGGCATCGTGGGGTGGCCCTCAGCTTCCCCACTCACTGTGGGAAGTTTCCTTAGTGTCTCTGAGCCTGTTTCCTCATCCGTTGCCTGAGGATAAACCTGCTTCAGGATTGTTGGTGAAAAGACTTCCCTCACCTAGCTTCTGTAACGCCACTGCATGCCACCACTGCTGAGTACTGTTTGTTTGCTAGGTTGGTGTCATTCTCATTTTACCAGAAAGTGAAGCTCORF Start: ATG at 41ORF Stop: TGA at 3944SEQ ID NO: 2401301 aaMW at 146115.7 kDNOV85a,MNNYVLNDEIGQGAFSTIYKGRYRTTTEFYAIASIDKKRRERVVNCVQLLRSMHHSNVCG59704-01 Protein SequenceIEFHNWYETNNHLWIITEYCTGGDMSTILRSNINLTTQAVQAFGRDVAMGLMYIHSKGVVYNDLQTRNLLMDSAAMLRFHDFSLACLFQDAATRPLVGTPLYMAPELFMADRPLYSMASDLWSFGCVLHELATGKPPFAASDLETLLGDILTSPTPAVPGAPESFQTLLCGLLEKDPLKRYAWVDVVRSEFWDEPLPLPSNGFPSQVAWEDYKRSRSGRGASQYNWTDSDVRVAVAHAVGAAKSNASTHNVEERERAAATLNVAKELDFTASAAMLLERLPERTQERAAHATGHVATAHGSLVHGCPSTASAATSPRRSRTRRRCSRLWKRSKPLSRASSRGCPSTSLRHPGMRERHWTGLSQKLGMKLVPGDTLMLLEDCEPLLAHRDTIISYCEVAAKESQIEMTLKDMRAKWETKCFIIEAYKETGTYILKDTSEVVELLDEHLNVVQQLQFSPFKGYFEESITDWERSLNLISDILEQWLECQRAWRYLEPILNSEDIAMQLPRLSTLFEKVDRTWRRVMGNAHAQPNALEYCIGTNKLLDHLREANRLLEVLQHLMAQKVNVAAVGPTGTGKSISLARLVLGGGMPANFLGLNFTFSAQTKCTVLQNSLMAKFDKRRSHVYGAPAGKHFLIFIDDANLPQPEKYGAQPPVELLRQMLAQGGFYNFTGGIKWSSIIDCSLALAMGPPGGGRSRVSNRFMRYFNYLAFPEMSDMSKRTILQAILVGGLAQSGLADRLANVASAVVDSTLRVFRKCTQVFLPTPAHVHYSFNMRDVMRVFPLLYTADKSVLQSEESIVRLWMHEMQRVFYDRLVDATDKGLFIEYLNAELPSMGVDKSYNEVVKADRLIFADVLSDKGVYEQITDMNALTTRMNELLEAYNDENEVKMNLVLFLDAIEHVCRISRVLRLPNGHCLLLGVGGSGRKSLTRLACSLIAEMEVFTIELSKNFGVKEWHESLAKLLLECGKDEKKRTFLFADTQLAHPTFLEDVAGLLTSGDVPNLFEDQDIELINDKFRGVCLSENLPTTKVSVYARFVKEARANLHLVLAFSPIGEAFRSRLRMFPSLIACCTIDWFAEWPSEALLSVAAVQLNAGDVTDVMGAASHADLPGCFQAVHRAAAEVTERFFTETRRRSYVTPTSYLSLLSNFKVMAAAKRRFVREQRGRLEKGLEKLRHTEVQVAELEAQLKAQQPVLVQKKAEIQSMMERLTVDRKEAAVKEADARREAQLPGGRAAYGGEDDE


[0770] Further analysis of the NOV85a protein yielded the following properties shown in Table 85B.
446TABLE 85BProtein Sequence Properties NOV85aPSort0.8800 probability located in nucleus; 0.3562 probabilityanalysis:located in microbody (peroxisome); 0.1671 probability locatedin lysosome (lumen); 0.1000 probability located inmitochondrial matrix spaceSignalPNo Known Signal Sequence Predictedanalysis:


[0771] A search of the NOV85a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 85C.
447TABLE 85CGeneseq Results for NOV85aNOV85aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAM79863Human protein SEQ ID NO 3509-602 . . . 1287218/692 (31%)1e−89Homo sapiens, 2127 aa.168 . . . 847347/692 (49%)[WO200157190-A2,9 AUG. 2001]AAM79862Human protein SEQ ID NO 3508-602 . . . 1287218/692 (31%)1e−89Homo sapiens, 2127 aa.168 . . . 847347/692 (49%)[WO200157190-A2,9 AUG. 2001]AAM78879Human protein SEQ ID NO 1541-602 . . . 1287218/692 (31%)1e−89Homo sapiens, 2143 aa.108 . . . 787347/692 (49%)[WO200157190-A2,9 AUG. 2001]AAM78878Human protein SEQ ID NO 1540-602 . . . 1287218/692 (31%)1e−89Homo sapiens, 2067 aa.108 . . . 787347/692 (49%)[WO200157190-A2,9 AUG. 2001]AAM80293Human protein SEQ ID NO 3945-910 . . . 1293153/393 (38%)5e−70Homo sapiens, 1774 aa. 33 . . . 405227/393 (56%)[WO200157190-A2,9 AUG. 2001]


[0772] In a BLAST search of public sequence databases, the NOV85a protein was found to have homology to the proteins shown in the BLASTP data in Table 85D.
448TABLE 85DPublic BLASTP Results for NOV85aNOV85AIdentities/ProteinResidues/Similarities forAccessionMatchthe MatchedExpectNumberProtein/Organism/LengthResiduesPortionValueAAL37427CILIARY DYNEIN HEAVY 628 . . . 1293271/692 (39%)e−132CHAIN 7 - Homo sapiens1975 . . . 2655395/692 (56%)(Human), 4024 aa.Q27812DYNEIN HEAVY CHAIN 601 . . . 1247264/667 (39%)e−127ISOTYPE 7B (EC 3.6.1.3) - 654 . . . 1310389/667 (57%)Tripneustes gratilla (Hawaian seaurchin), 1314 aa (fragment).Q9MBF81 BETA DYNEIN HEAVY 611 . . . 1293257/693 (37%)e−117CHAIN - Chlamydomonas2486 . . . 3159377/693 (54%)reinhardtii, 4513 aa.Q9VJC6DHC36C PROTEIN - Drosophila 596 . . . 1275249/699 (35%)e−116melanogaster (Fruit fly), 4010 aa.1913 . . . 2604383/699 (54%)Q9VWZ3DHC16F PROTEIN - Drosophila 618 . . . 1301248/704 (35%)e−108melanogaster (Fruit fly), 4081 aa.2022 . . . 2709380/704 (53%)


[0773] PFam analysis predicts that the NOV85a protein contains the domains shown in the Table 85E.
449TABLE 85EDomain Analysis of NOV85aIdentities/SimilaritiesNOV85a Matchfor theExpectPfam DomainRegionMatched RegionValuepkinase: domain 1 of 1 4 . . . 25080/286(28%)6.8e−62190/286(66%)DEAD: domain 1 of 1613 . . . 6377/25(28%)0.8322/25(88%)dNK: domain 1 of 1 865 . . . 102032/179(18%)6.8 101/179(56%)


[0774] The NOV86 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 86A.
450TABLE 86ANOV86 Sequence AnalysisSEQ ID NO: 2411420 bpNOV86a,GTCCAGCTTTAGCTCTCTGCTCGCCGCCGCCGCTGTCGCCGCCACCTCCTCTGATCTACG59628-01 DNA SequenceCGAAAGTCATGTTACCCAACACCGGGAGGCTGGCAGGATGTACAGTTTTTTATCACAGGTGCAAGCCGTGGCATTGGCAAAGCTATTGCATTGAAAGCAGCAAAGGATGGAGCAAATATTGTTATTGCTGCAAAGACCGCCCAGCCACATCCAAAACTTCTAGGCACAATCTATACTGCTGCTGAAGAAATTGAAGCAGTTGGAGGAAAGGCCTTGCCATGTATTGTTGATGTGAGAGATGAACAGCAGATCAGTGCTGCAGTGGAGAAAGCCATCAAGAAATTTGGAGGAATTGATATTCTGGTAAATAATGCCAGTGCCATTAGTTTGACCAATACATTGGACACACCTACCAAGAGATTGGATCTGATGATGAACGTGAACACCAGAGGCACCTACCTTGCATCTAAAGCATGTATTCCTTATTTGAAAAAGAGCAAAGTTGCTCATATCCTCAATATCAGTCCACCACTGAACCTAAATCCAGTTTGGTTCAAACAGCACTGTGCTTATACCATTGCTAAGTATGGTATGTCTATGTATGTGCTTGGAATGGCAGAAGAATTTAAAGGTGAAATTGCAGTCAATGCATTATGGCCTAAAACAGCCATACACACTGCTGCTATGGATATGCTGGGAGGACCTGGTATCGAAAGCCAGTGTAGAAAAGTTGATATCATTGCAGATGCAGCATATTCCATTTTCCAAAAGCCAAAAAGTTTTACTGGCAACTTTGTCATTGATGAAAATATCTTAAAAGAAGAAGGAATAGAAAATTTTGACGTTTATGCAATTAAACCAGGTCATCCTTTGCAACCAGATTTCTTCTTAGATGAATACCCAGAAGCAGTTAGCAAGAAAGTGGAATCAACTGGTGCTGTTCCAGAATTCAAAGAAGAGAAACTGCAGCTGCAACCAAAACCACGTTCTGGAGCTGTGGAAGAAACATTTAGAATTGTTAAGGACTCTCTCAGTGATGATGTTGTTAAAGCCACTCAAGCAATCTATCTGTTTGAACTCTCCGGTGAAGATGGTGGCACGTGGTTTCTTGATCTGAAAAGCAAGGGTGGGAATGTCGGATATGGAGAGCCTTCTGATCAGGCAGATGTGGTGATGAGTATGACTACTGATGACTTTGTAAAAATGTTTTCAGGTAAACTAAAACCAACAATGGCATTCATGTCAGGGAAATTGAAGATTAAAGGTAACATGGCCCTAGCAATCAAATTGGAGAAGCTAATGAATCAGATGAATGCCAGACTGTGAAGGAAAATATAAAAAAAAAGTCGACTGCTATGCTCAAAAAGTAAAAAAAGCTCAACAGTTAAAATCTAATGTTTGTTTTCTTTCCTGTTATATTATAORF Start: ATG at 67ORF Stop: TGA at 1321SEQ ID NO: 242418 aaMW at 45394.2 kDNOV86a,MLPNTGRLAGCTVFITGASRGIGKAIALKAAKDGANIVIAAKTAQPHPKLLGTIYTAACG59628-01 Protein SequenceEEIEAVGGKALPCIVDVRDEQQISAAVEKAIKKFGGIDILVNNASAISLTNTLDTPTKRLDLMMNVNTRGTYLASKACIPYLKKSKVAHILNISPPLNLNPVWFKQHCAYTIAKYGMSMYVLGMAEEFKGEIAVNALWPKTAIHTAAMDMLGGPGIESQCRKVDIIADAAYSIFQKPKSFTGNFVIDENILKEEGIENFDVYAIKPGHPLQPDFFLDEYPEAVSKKVESTGAVPEFKEEKLQLQPKPRSGAVEETFRIVKDSLSDDVVKATQAIYLFELSGEDGGTWFLDLKSKGGNVGYGEPSDQADVVMSMTTDDFVKMFSGKLKPTMAFMSGKLKIKGNMALAIKLEKLMNQMNARL


[0775] Further analysis of the NOV86a protein yielded the following properties shown in Table 86B.
451TABLE 86BProtein Sequence Properties NOV86aPSort0.5500 probability located in endoplasmic reticulumanalysis:(membrane); 0.5000 probability located in microbody(peroxisome); 0.1900 probability located inlysosome (lumen); 0.1000 probability locatedin endoplasmic reticulum (lumen)SignalPNo Known Signal Sequence Predictedanalysis:


[0776] A search of the NOV86a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 86C.
452TABLE 86CGeneseq Results for NOV86aNOV86aIdentities/Residues/SimilaritiesGeneseqProtein/Organism/LengthMatchfor theExpectIdentifier[Patent #, Date]ResiduesMatched RegionValueAAG81260Human AFP protein sequence SEQ1 . . . 418418/418(100%)0.0ID NO:38 - Homo sapiens, 418 aa.1 . . . 418418/418(100%)[WO200129221-A2, 26 APR2001]AAB84367Amino acid sequence of human1 . . . 418418/418(100%)0.0alcohol dehydrogenase 21612 -1 . . . 418418/418(100%)Homo sapiens, 418 aa.[WO200144446-A2, 21 JUN 2001]AAG81258Human AFP protein sequence SEQ1 . . . 382382/382(100%)0.0ID NO:34 - Homo sapiens, 383 aa.1 . . . 382382/382(100%)[WO200129221-A2, 26 APR2001]ABB10251Human cDNA SEQ ID NO: 559 -141 . . . 418 271/278(97%)e−156Homo sapiens, 278 aa.1 . . . 278274/278(98%)[WO200154474-A2, 2 AUG2001]AAU23020Novel human enzyme polypeptide141 . . . 418 271/278(97%)e−156#106 - Homo sapiens, 278 aa.1 . . . 278274/278(98%)[WO200155301-A2, 2 AUG2001]


[0777] In a BLAST search of public sequence databases, the NOV86a protein was found to have homology to the proteins shown in the BLASTP data in Table 86D.
453TABLE 86DPublic BLASTP Results for NOV86aNOV86AIdentities/ProteinResidues/SimilaritiesAccessionMatchfor theExpectNumberProtein/Organism/LengthResiduesMatched PortionValueCAC38510SEQUENCE 37 FROM1 . . . 418418/418(100%)0.0PATENT WO0129221 - Homo1 . . . 418418/418(100%)sapiens (Human), 418 aa.CAC38508SEQUENCE 33 FROM1 . . . 382382/382(100%)0.0PATENT WO0129221 - Homo1 . . . 382382/382(100%)sapiens (Human), 383 aa.Q99LV2HYPOTHETICAL 54.9 KDA1 . . . 418355/496(71%)0.0PROTEIN - Mus musculus1 . . . 496390/496(78%)(Mouse), 496 aa.Q9BT58SIMILAR TO RIKEN CDNA163 . . . 418 253/256(98%)e−1432610207116 GENE - Homo90 . . . 345 254/256(98%)sapiens (Human), 345 aa.Q9VB10CG5590 PROTEIN (GH01709P) -4 . . . 418238/422(56%)e−128Drosophila melanogaster (Fruit3 . . . 412300/422(70%)fly), 412 aa.


[0778] PFam analysis predicts that the NOV86a protein contains the domains shown in the Table 86E.
454TABLE 86EDomain Analysis of NOV86aIdentities/SimilaritiesNOV86a Matchfor theExpectPfam DomainRegionMatched RegionValuebeta-lactamase:222 . . . 2364/15(27%)6.5domain 1 of 114/15(93%)adh_short: 9 . . . 32174/339(22%)2.4e−29domain 1 of 1211/339(62%)SCP2: domain 1 of 1306 . . . 41541/114(36%)1.5e−2587/114(76%)



Example 87

[0779] The NOV87 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 87A.
455TABLE 87ANOV87 Sequence AnalysisSEQ ID NO: 243888 bpNOV87a,TTCAACAAGGGCCCCTCCTACAGGCTCTTGGCGGACGTCCAGAACAGGCTTCTGTTCACG59516-01 DNA SequenceAATATGACTCCCAGAAGGAGGCAGAGCTCCGCAGCTGGATCAAGGGATTCACTGGCCTCTCCATCCGCCCCGACTTCCAGAAGGGCCTGAAGGACGGGATTATTTTATGCACACTCGTGAACAAACTGCAGCCGGGCTCAGTCCCCAAGATCAACGGCTTCCGTGTAGAACTGGCACCAGCTAGAAAACCTCTCCAACATCCTCAAGGCAATGGTCAGCTACGGCATGATCCCGTGGACCTATTTGAGGCCAACGACCTGTTTGAGAGTGGGAACAATATGCAGGTGCGGGTGTCTCTTCTCGCCCTGGCAGGGAAGGCCAAGACTAAGGGGCTGCAGAGCGGGGTGGACATCCGTGACAAGTACTCAGAGAAGCAGAACTTCAACGACACCACCATGAAGGCCAGGCTGTGCGTCATCCGGCTGCAGATTACCAACAAATGTGCCAGCCAGTCAGGCATGACCGCATACGTCACGAGGAGGCATCTCTACGACCCCAAGAACCGCATCCTGCCCCCCATGGACAACTCGACCATCAGCCTCCGGATGGGTACAAACAAGTGCGCCAGCCAGGTGGGCATGACGGCTCCCGGGAACCAGTGGCACATCTATGACACCAAGTTGGGAATCGACAAGTGTGAGAACTCCTCCATGTCCCTGAAGATGGGCTACACGCAGGTCGCCAATCACAGCAGACAGGTCTTTGGCCTAGGCCGGCAAATATATGAACCCAAGTACCAGCCGGGTGGCCCAGTGGCCCACGGGGCTCCCTCCGCCGGCAACTGCCCAGGGCCAGGGGAGGCCCCTTAGTACCAGGAGGAGACCAGCTACORF Start: TTC at 1ORF Stop: TAG at 865SEQ ID NO: 244288 aaMW at 31831.2 kDNOV87a,FNKGPSYRLLADVQNRLLFKYDSQKEAELRSWIKGFTGLSIRPDFQKGLKDGIILCTLCG59516-01 Protein SequenceVNKLQPGSVPKINGFRVELAPARKPLQHPQGNGQLRHDPVDLFEANDLFESGNNMQVRVSLLALAGKAKTKGLQSGVDIRDKYSEKQNFNDTTMKARLCVIRLQITNKCASQSGMTAYVTRRHLYDPKNRILPPMDNSTISLRMGTNKCASQVGMTAPGNQWHIYDTKLGIDKCENSSMSLKMGYTQVANHSRQVFGLGRQIYEPKYQPGGPVAHGAPSAGNCPGPGEAPSEQ ID NO: 245888 bpNOV87b,TTCAACAAGGGCCCCTCCTACAGGCTCTTGGCGGACGTCCAGAACAGGCTTCTGTTCACG59516-02 DNA SequenceAATATGACTCCCAGAAGGAGGCAGAGCTCCGCAGCTGGATCAAGGGATTCACTGGCCTCTCCATCCGCCCCGACTTCCAGAAGGGCCTGAAGGACGGGATTATTTTATGCACACTCGTGAACAAACTGCAGCCGGGCTCAGTCCCCAAGATCAACGGCTTCCGTGTAGAACTGGCACCAGCTAGAAAACCTCTCCAACATCCTCAAGGCAATGGTCAGCTACGGCATGATCCCGTGGACCTATTTGAGGCCAACGACCTGTTTGAGAGTGGGAACAATATGCAGGTGCGGGTGTCTCTTCTCGCCCTGGCAGGGAAGGCCAAGACTAAGGGGCTGCAGAGCGGGGTGGACATCCGTGACAAGTACTCAGAGAAGCAGAACTTCAACGACACCACCATGAAGGCCAGGCTGTGCGTCATCCGGCTGCAGATTACCAACAAATGTGCCAGCCAGTCAGGCATGACCGCATACGTCACGAGGAGGCATCTCTACGACCCCAAGAACCGCATCCTGCCCCCCATGGACAACTCGACCATCAGCCTCCGGATGGGTACAAACAAGTGCGCCAGCCAGGTGGGCATGACGGCTCCCGGGAACCAGTGGCACATCTATGACACCAAGTTGGGAATCGACAAGTGTGAGAACTCCTCCATGTCCCTGAAGATGGGCTACACGCAGGTCGCCAATCACAGCAGACAGGTCTTTGGCCTAGGCCGGCAAATATATGAACCCAAGTACCAGCCGGGTGGCCCAGTGGCCCACGGGGCTCCCTCCGCCGGCAACTGCCCAGGGCCAGGGGAGGCCCCTTAGTACCAGGAGGAGACCAGCTACORF Start: TTC at 1ORF Stop: TAG at 865SEQ ID NO: 246288 aaMW at 31831.2 kDNOV87b,FNKGPSYRLLADVQNRLLFKYDSQKEAELRSWIKGFTGLSIRPDFQKGLKDGIILCTLCG59516-02 Protein SequenceVNKLQPGSVPKINGFRVELAPARKPLQHPQGNGQLRHDPVDLFEANDLFESGNNMQVRVSLLALAGKAKTKGLQSGVDIRDKYSEKQNFNDTTMKARLCVIRLQITNKCASQSGMTENSSMSLKMGYTQVANHSRQVFGLGRQIYEPKYQPGGPVAHGAPSAGNCPGPGEAP


[0780] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 87B.
456TABLE 87BComparison of NOV87a against NOV87b.Identities/SimilaritiesProteinNOV87a Residues/for theSequenceMatch ResiduesMatched RegionNOV87b1 . . . 288288/288 (100%)1 . . . 288288/288 (100%)


[0781] Further analysis of the NOV87a protein yielded the following properties shown in Table 87C.
457TABLE 87CProtein Sequence Properties NOV87aPSort0.4500 probability located in cytoplasm; 0.3000 probabilityanalysis:located in microbody (peroxisome); 0.2110 probabilitylocated in lysosome (lumen); 0.1000 probability located inmitochondrial matrix spaceSignalPNo Known Signal Sequence Predictedanalysis:


[0782] A search of the NOV87a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 87D.
458TABLE 87DGeneseq Results for NOV87aNOV87aIdentities/Residues/SimilaritiesGeneseqProtein/Organism/LengthMatchfor theExpectIdentifier[Patent #, Date]ResiduesMatched RegionValueAAR94888Carponin - Homo sapiens, 297 aa.1 . . . 265136/269(50%)7e−63[JP08073380-A, 19 MAR 1996]6 . . . 272176/269(64%)AAR72588Carponin protein - Homo sapiens,1 . . . 265136/269(50%)7e−63297 aa. [WO9509010-A, 6 APR6 . . . 272176/269(64%)1995]AAB43807Human cancer associated protein164 . . . 273 67/113(59%)6e−30sequence SEQ ID NO:1252 - Homo4 . . . 11682/113(72%)sapiens, 163 aa. [WO200055350-A1, 21 SEP 2000]AAM73074Human bone marrow expressed157 . . . 225 49/70(70%)4e−21probe encoded protein SEQ ID NO:2 . . . 71 55/70(78%)33380 - Homo sapiens, 71 aa.[WO200157276-A2, 09 AUG 2001]AAM60434Human brain expressed single exon157 . . . 225 49/70(70%)4e−21probe encoded protein SEQ ID NO:2 . . . 71 55/70(78%)32539 - Homo sapiens, 71 aa.[WO200157275-A2, 9 AUG 2001]


[0783] In a BLAST search of public sequence databases, the NOV87a protein was found to have homology to the proteins shown in the BLASTP data in Table 87E.
459TABLE 87EPublic BLASTP Results for NOV87aNOV87AIdentities/ProteinResidues/SimilaritiesAccessionMatchfor theExpectNumberProtein/Organism/LengthResiduesMatched PortionValueQ08094Calponin H2, smooth muscle - Sus1 . . . 287219/291 (75%) e−116scrofa (Pig), 296 aa (fragment).6 . . . 296237/291 (81%)Q99439Calponin H2, smooth muscle1 . . . 288218/292 (74%) e−115(Neutral calponin) - Homo sapiens6 . . . 297235/292 (79%)(Human), 309 aa.Q08093Calponin H2, smooth muscle -1 . . . 288214/291 (73%) e−112Mus musculus (Mouse), 305 aa.6 . . . 293231/291 (78%)O93547CALPONIN H3 - Xenopus laevis1 . . . 269179/273 (65%)6e−91(African clawed frog), 295 aa.5 . . . 276208/273 (75%)Q922F8UNKNOWN (PROTEIN FOR59 . . . 288 166/233 (71%)8e−83MGC:8135) - Mus musculus1 . . . 230179/233 (76%)(Mouse), 242 aa.


[0784] PFam analysis predicts that the NOV87a protein contains the domains shown in the Table 87F.
460TABLE 87FDomain Analysis of NOV87aIdentities/SimilaritiesNOV87a Matchfor theExpectPfam DomainRegionMatched RegionValueCH: domain 1 of 1 23 . . . 12327/124(22%)0.06865/124(52%)calponin:159 . . . 18317/26(65%)3.8e−07domain 1 of 221/26(81%)calponin:198 . . . 22315/26(58%)  3e−08domain 2 of 219/26(73%)



Example 88

[0785] The NOV88 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 88A.
461TABLE 88ANOV 88 Sequence AnalysisSEQ ID NO: 2472213 bpNOV88a,CGTGAGGCACCCACTCTGGGAGCACAGAGAGCTCAGGTAGCCTGCCTAGATGGCGGCGCG59671-02 DNA SequenceCGCACCCTGGGCCGCGGCGTCGGGAGGCTGCTGGGCAGCCTGCGAGGGCTCTCGGGGCAGCCCGCGCGGCCGCCGTGCGGGGTGAGCGCGCCGCGCAGGGCGGCCTCGGGACCCTCGGGCAGCGCTCCCGCAGTTGCAGCAGCAGCAGCACAGCCAGGCTCGTATCCCGCGCTGAGTGCACAGGCAGCCCGGGAGCCGGCCGCCTTCTGGGGGCCTCTGGCGCGGGACACTCTCGTGTGGGACACCCCCTACCACACCGTCTGGGACTGCGACTTCAGCACTGGCAAGATCGGCTGGTTCCTGGGAGGCCAGTTAAATGTCTCTGTCAACTGCTTGGACCAGCATGTTCGGAAGTCCCCCGAGAGCGTTGCTTTGATCTGGGAGCGCGATGAGCCTGGAACGGAAGTGAGGATCACCTACAGGGAACTACTGGAGACCACGTGCCGCCTGGCCAACACGCTGAAGAGGCATGGAGTCCACCGTGGGGACCGTGTTGCCATCTACATGCCCGTGTCCCCATTGGCTGTGGCAGCAATGCTGGCCTGTGCCAGGATCGGAGCTGTCCACACAGTCATCTTTGCTGGCTTCAGTGCAGAGTCCTTGGCTGGGAGGATCAATGATGCCAAGTGCAAGGTGGTTATCACCTTCAACCAAGGACTCCGGGGTGGGCGCGTGGTGGAGCTGAAGAAAATAGTGGATGAGGCTGTGAAGCACTGCCCCACCGTGCAGCATGTCCTGGTGGCTCACAGGACAGACAACAAGGTCCACATGGGGGATCTGGACGTCCCGCTGGAGCAGGAAATGGCCAAGGAGGACCCTGTTTGCGCCCCAGAGAGCATGGGCAGTGAGGACATGCTCTTCATGCTGTACACCTCAGGGAGCACCGGAATGCCCAAGGGCATCGTCCATACCCAGGCAGGCTACCTGCTCTATGCCGCCCTGACTCACAAGCTTGTGTTTGACCACCAGCCAGGTGACATCTTTGGCTGTGTGGCCGACATCGGTTGGATTACAGGACACAGCTACGTGGTGTATGGGCCTCTCTGCAATGGTGCCACCAGCGTCCTTTTTGAGAGCACCCCAGTTTATCCCAATGCTGGTCGGTACTGGGAGACAGTAGAGAGGTTGAAGATCAATCAGTTCTATGGCGCCCCAACGGCTGTCCGGCTGTTGCTGAAATACGGTGATGCCTGGGTGAAGAAGTATGATCGCTCCTCCCTGCGGACCCTGGGGTCAGTGGGAGAGCCCATCAACTGTGAGGCCTGGGAGTGGCTTCACAGGGTGGTGGGGGACAGCAGGTGCACGCTGGTGGACACCTGGTGGCAGACAGAAACAGGTGGCATCTGCATCGCACCACGGCCCTCGGAAGAAGGGGCGGAAATCCTCCCTGCCATGGCGATGAGGCCCTTCTTTGGCATCGTCCCCGTCCTCATGGATGAGAAGGGCAGCGTCGTGGAGGGCAGCAACGTCTCCGGGGCCCTGTGCATCTCCCAGGCCTGGCCGGGCATGGCCAGGACCATCTATGGCGACCACCAGCGATTTGTGGACGCCTACTTCAAGGCCTACCCAGGCTATTACTTCACTGGAGACGGGGCTTACCGAACTGAGGGCGGCTATTACCAGATCACAGGGCGGATGGATGATGTCATCAACATCAGTGGCCACCGGCTGGGGACCGCAGAGATTGAGGACGCCATCGCCGACCACCCTGCAGTACCAGAAAGTGCTGTCATTGGCTACCCCCACGACATCAAAGGAGAAGCTGCCTTTGCCTTCATTGTGGTGAAAGATAGTGCGGGTGACTCAGATGTGGTGGTGCAGGAGCTCAAGTCCATGGTGGCCACCAAGATCGCCAAATATGCTGTGCCTGATGAGATCCTGGTGGTGAAACGTCTTCCAAAAACCAGGTCTGGGAAGGTCATGCGGCGGCTCCTGAGGAAGATCATCACTAGTGAGGCCCAGGAGCTGGGAGACACTACCACCTTGGAGGACCCCAGCATCATCGCAGAGATCCTGAGTGTCTACCAGAAGTGCAAGGACAAGCAGGCTGCTGCTAAGTGAGCTGGCACCTTGTGGGGCTCTTGGGATGGGCGGGCACCCAAGCCCTGGCTTGTCCTTCCCAGAAGGTACCCCTGAGGTTGGCGTCTTCCTACGTORF Start: ATG at 50ORF Stop: TGA at 2117SEQ ID NO: 248689 aaMW at 74855.9 kDNOV88a,MAARTLGRGVGRLLGSLRGLSGQPARPPCGVSAPRRAASGPSGSAPAVAAAAAQPGSYCG59671-02 Protein SequencePALSAQAAREPAAFWGPLARDTLVWDTPYHTVWDCDFSTGKIGWFLGGQLNVSVNCLDQHVRKSPESVALIWERDEPGTEVRITYRELLETTCRLANTLKRHGVHRGDRVAIYMPVSPLAVAAMLACARIGAVHTVIFAGFSAESLAGRINDAKCKVVITFNQGLRGGRVVELKKIVDEAVKHCPTVQHVLVAHRTDNKVHMGDLDVPLEQEMAKEDPVCAPESMGSEDMLFMLYTSGSTGMPKGIVHTQAGYLLYAALTHKLVFDHQPGDIFGCVADIGWITGHSYVVYGPLCNGATSVLFESTPVYPNAGRYWETVERLKINQFYGAPTAVRLLLKYGDAWVKKYDRSSLRTLGSVGEPINCEAWEWLHRVVGDSRCTLVDTWWQTETGGICIAPRPSEEGAEILPAMAMRPFFGIVPVLMDEKGSVVEGSNVSGALCISQAWPGMARTIYGDHQRFVDAYFKAYPGYYFTGDGAYRTEGGYYQITGRMDDVINISGHRLGTAEIEDAIADHPAVPESAVIGYPHDIKGEAAFAFIVVKDSAGDSVVVQELKSMVATKIAKYAVPDEILVVKKRLPKTRSGKVMRRLLRKIITSEAQELGDTTTLEDPSIIAEILSVYQKCKDKQAAAK


[0786] Further analysis of the NOV88a protein yielded the following properties shown in Table 88B.
462TABLE 88BProtein Sequence Properties NOV88aPSort0.6500 probability located in plasma membrane; 0.6000analysis:probability located in nucleus; 0.4340 probabilitylocated in mitochondrial inner membrane; 0.3000probability located in Golgi bodySignalPLikely cleavage site between residues 23 and 24analysis:


[0787] A search of the NOV88a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 88C.
463TABLE 88CGeneseq Results for NOV88aNOV88aIdentities/Residues/SimilaritiesGeneseqProtein/Organism/LengthMatchfor theExpectIdentifier[Patent #, Date]ResiduesMatched RegionValueAAU23058Novel human enzyme polypeptide26 . . . 689663/664(99%)0.0#144 - Homo sapiens, 664 aa. 1 . . . 664663/664(99%)[WO200155301-A2, 2 AUG2001]AAB34712Human secreted protein encoded172 . . . 689 518/518(100%)0.0by DNA clone vo9 1 - Homo 1 . . . 518518/518(100%)sapiens, 518 aa. [WO200055375-A1, 21 SEP 2000]AAU23050Novel human enzyme polypeptide224 . . . 689 459/466(98%)0.0#136 - Homo sapiens, 479 aa.18 . . . 479461/466(98%)[WO200155301-A2, 2 AUG2001]ABB12253Human acetate-coA ligase 1 . . . 446446/446(100%)0.0homologue, SEQ ID NO:2623 - 1 . . . 446446/446(100%)Homo sapiens, 446 aa.[WO200157188-A2, 9 AUG2001]AAR23968facA gene product - Penicillium58 . . . 684305/629(48%)e−175chrysogenum, 669 aa.45 . . . 669407/629(64%)[WO9207079-A, 30 APR 1992]


[0788] In a BLAST search of public sequence databases, the NOV88a protein was found to have homology to the proteins shown in the BLASTP data in Table 88D.
464TABLE 88DPublic BLASTP Results for NOV88aNOV88AIdentities/ProteinResidues/SimilaritiesAccessionMatchfor theExpectNumberProtein/Organism/LengthResiduesMatched PortionValueQ99NB1ACETYL-COA SYNTHETASE 2 -1 . . . 687599/687(87%)0.0Mus musculus (Mouse), 682 aa.1 . . . 680638/687(92%)Q9BEA3ACETYL-COA SYNTHETASE 2 -1 . . . 689575/689(83%)0.0Bos taurus (Bovine), 675 aa.1 . . . 675625/689(90%)Q9NUB1DJ568C11.3 (NOVEL AMP-212 . . . 689 478/478(100%)0.0BINDING ENZYME SIMILAR TO1 . . . 478478/478(100%)ACETYL-COENZYME ALIGASE)) - Homo sapiens (Human),478 aa (fragment).Q96JI1KIAA1846 PROTEIN - Homo336 . . . 689 354/354(100%)0.0sapiens (Human), 354 aa (fragment).1 . . . 354354/354(100%)Q9HV66ACETYL-COENZYME A58 . . . 675 326/619(52%)0.0SYNTHETASE - Pseudomonas24 . . . 639 433/619(69%)aeruginosa, 645 aa.


[0789] PFam analysis predicts that the NOV88a protein contains the domains shown in the Table 88E.
465TABLE 88EDomain Analysis of NOV88aIdentities/SimilaritiesNOV88a Matchfor theExpectPfam DomainRegionMatched RegionValueAMP-binding:142 . . . 580121/441 (27%)7.1e−117domain 1 of 1341/441 (77%)



Example 89

[0790] The NOV89 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 89A.
466TABLE 89ANOV89 Sequence AnalysisSEQ ID NO: 2491268 bpNOV89a,ACTTCTTTCTTTTCTGTTTCAGAGTTACTGATTTATTCTTGAGATTCCTCTACTCTCGCG56870-01 DNA SequenceTTATCTGACCTCATGGATGAACTTCAGGATGTTCAGCTCACAGAGATCAAACCACTTCTAAATGATAAGAATGGTACAAGAAACTTCCAGGACTTTGACTGTCAGGAACATGATATAGAAACAACTCATGGTGTGGTCCACGTCACTATAAGAGGCTTACCCAAAGGAAACAGACCAGTTATACTAACATATCATGACATTGGCCTCAACCGTAAATCCTGTTTCAATGCATTCTTTAACTTTGAGGATATGCAAGAGATCACCCAGCACTTTGCTGTCTGTCATGTGGATGCCCCAGGCCAGCAGGAAGGTGCACCCTCTTTCCCAACAGGGTATCAGTACCCCACAATGGATGAGCTGGCTGAAATGCTGCCTCCTGTTCTTACCCACCTAAGCCTGAAAAGCATCATTGGAATTGGAGTTGGAGCTGGAGCTTACATCCTCAGCAGATTTGCACTCAACCATCCAGAGCTTGTGGAAGGCCTTGTGCTCATTAATGTTGACCCTTGCGCTAAAGGCTGGATTGACTGGGCAGCTTCCAAACTCTCTGGCCTGACAACCAATGTTGTGGACATTATTTTGGCTCATCACTTTGGGCAGGAAGAGTTACAGGCCAACCTGGACCTGATCCAAACCTACAGAATGCATATTGCCCAAGACATCAACCAAGACAACCTGCAGCTCTTCTTGAATTCCTACAATGGGCGCAGAGACCTGGAGATCGAAAGACCCATACTGGGCCAAAATGATAACAAATCAAAAACATTAAAGTGTTCTACTTTACTGGTGGTAGGGGACAATTCGCCTGCAGTTGAGGCTGTGGTCGAATGCAATTCCCGCCTGAACCCTATAAATACAACTTTGCTAAAGATGGCGGACTGTGGGGGACTGCCCCAGGTAGTTCAGCCTGGGAAGCTCACCGAGGCCTTCAAGTACTTTTTGCAGGGAATGGGCTACGTCCCGTCTGCCAGCATGACTCGGCTCGCCCGATCACGAACCCACTCAACCTCGAGTAGCCTCGGCTCTGGAGAAAGTCCCTTCAGCCGGTCTGTCACCAGCAATCAGTCAGATGGAACTCAAGAATCCTGTGAGTCCCCTGATGTCCTGGACAGACACCAGACCATGGAGGTGTCCTGCTAAGCAGATGCTCCTCCCCTGGACCATTGCAAGTCCATCCTTCAAATGACCACTCCATAATATAACATTTCATORF Start: ATG at 71ORF Stop: TAA at 1196SEQ ID NO: 250375 aaMW at 41413.3 kDNOV89a,MDELQDVQLTEIKPLLNDKNGTRNFQDFDCQEHDIETTHGVVHVTIRGLPKGNRPVILCG56870-01 Protein SequenceTYHDIGLNRKSCFNAFFNFEDMQEITQHFAVCHVDAPGQQEGAPSFPTGYQYPTMDELAEMLPPVLTHLSLKSIIGIGVGAGAYILSRFALNHPELVEGLVLINVDPCAKGWIDWAASKLSGLTTNVVDIILAHHFGQEELQANLDLIQTYRMHIAQDINQDNLQLFLNSYNGRRDLEIERPILGQNDNKSKTLKCSTLLVVGDNSPAVEAVVECNSRLNPINTTLLKMADCGGLPQVVQPGKLTEAFKYFLQGMGYVPSASMTRLARSRTHSTSSSLGSGESPFSRSVTSNQSDGTQESCESPDVLDRHQTMEVSCSEQ ID NO: 2511175 bpNOV89b,TCGTTATCTGACCTCATGGATGAACTTCAGGATGTTCAGCTCACAGAGATCAAACCACCG56870-02 DNA SequenceTTCTAAATGATAAGAATGGTACAAGAAACTTCCAGGACTTTGACTGTCAGGAACATGATATAGAAACAACTCATGGTGTGGTCCACGTCACTATAAGAGGCTTACCCAAAGGAAACAGACCAGTTATACTAACATATCATGACATTGGCCTCAACCATAAATCCTGTTTCAATGCATTCTTTAACTTTGAGGATATGCAAGAGATCACCCAGCACTTTGCTGTCTGTCATGTGGATGCCCCAGGCCAGCAGGAAGGTGCACCCTCTTTCCCAACAGGGTATCAGTACCCCACAATGGATGAGCTGGCTGAAGTGCTGCCTCCTGTTCTTACCCACCTAAGCCTGAAAAGCATCATTGGAATTGGAGTTGGAGCTGGAGCTTACATCCTCAGCAGATTTGCACTCAACCATCCAGAGCTTGTGGAAGGCCTTGTGCTCATTAATGTTGACCCTTGCGCTAAAGGCTGGATTGACTGGGCAGCTTCCAAACTCTCTGGCCTGACAACCAATGTTGTGGACATTATTTTGGCTCATCACTTTGGGCAGGAAGAGTTACAGGCCAACCTGGACCTGATCCAAACCTACAGAATGCATATTGCCCAAGACATCAACCAAGACAACCTGCAGCTCTTCTTGAATTCCTACAATGGACGCAGAGACCTGGAGATCGAAAGACCCATACTGGGCCAAAATGATAACAAATCAAAAACATTAAAGTGTTCTACTTTACTGGTGGTAGGGGACAATTCGCCTGCAGTTGAGGCTGTGGTCGAATGCAATTCCCGCCTGAACCCTATAAATACAACTTTGCTAAAGATGGCGGACTGTGGGGGACTGCCCCAGGTAGTTCAGCCTGGGAAGCTCACCGAGGCCTTCAAGTACTTTTTGCAGGGAATGGGCTACATACCATCTGCCAGCATGACTCGGCTCGCCCGATCACGAACCCACTCAACCTCGAGTAGCCTCGGCTCTGGAGAAAGTCCCTTCAGCCGGTCTGTCACCAGCAATCAGTCAGATGGAACTCAAGAATCCTGTGAGTCCCCTGATGTCCTGGACAGACACCAGACCATGGAGGTGTCCTGCTAAGCAGATGCTCCTCCCCTGGACCATTGCAAGTCORF Start: ATG at 16ORF Stop: TAA at 1141SEQ ID NO: 252375 aaMW at 41376.2 kDNOV89b,MDELQDVQLTEIKPLLNDKNGTRNFQDFDCQEHDIETTHGVVHVTIRGLPKGNRPVILCG56870-02 Protein SequenceTYHDIGLNHKSCFNAFFNFEDMQEITQHFAVCHVDAPGQQEGAPSFPTGYQYPTMDELAEVLPPVLTHLSLKSIIGIGVGAGAYILSRFALNHPELVEGLVLINVDPCAKGWIDWAASKLSGLTTNVVDIILAHHFGQEELQANLDLIQTYRMHIAQDINQDNLQLFLNSYNGRRDLEIERPILGQNDNKSKTLKCSTLLVVGDNSPAVEAVVECNSRLNPINTTLLKMADCGGLPQVVQPGKLTEAFKYFLQGMGYIPSASMTRLARSRTHSTSSSLGSGESPFSRSVTSNQSDGTQESCESPDVLDRHQTMEVSCSEQ ID NO: 2531232 bpNOV89c,ACTTCTTTCTTTTCTGTTTCAGAGTTACTGATTTATTCTTGAGATTCCTCTACTCTCGCG56870-03 DNA SequenceTTATCTGACCTCATGGATGAACTTCAGGATGTTCAGCTCACAGAGATCAAACCACTTCTAAATGATAAGGAACATGATATAGAAACAACTCATGGTGTGGTCCACGTCACTATAAGAGGCTTACCCAAAGGAAACAGACCAGTTATACTAACATATCATGACATTGGCCTCAACCATAAATCCTGTTTCAATGCATTCTTTAACTTTGAGGATATGCAAGAGATCACCCAGCACTTTGCTGTCTGTCATGTGGATGCCCCAGGCCAGCAGGAAGGTGCACCCTCTTTCCCAACAGGGTATCAGTACCCCACAATGGATGAGCTGGCTGAAATGCTGCCTCCTGTTCTTACCCACCTAAGCCTGAAAAGCATCATTGGAATTGGAGTTGGAGCTGGAGCTTACATCCTCAGCAGATTTGCACTCAACCATCCAGAGCTTGTGGAAGGCCTTGTGCTCATTAATGTTGACCCTTGCGCTAAAGGCTGGATTGACTGGGCAGCTTCCAAACTCTCTGGCCTGACAACCAATGTTGTGGACATTATTTTGGCTCATCACTTTGGGCAGGAAGAGTTACAGGCCAACCTGGACCTGATCCAAACCTACAGAATGCATATTGCCCAAGACATCAACCAAGACAACCTGCAGCTCTTCTTGAATTCCTACAATGGGCGCAGAGACCTGGAGATCGAAAGACCCATACTGGGCCAAAATGATAACAAATCAAAAACATTAAAGTGTTCTACTTTACTGGTGGTAGGGGACAATTCGCCTGCAGTTGAGGCTGTGGTCGAATGCAATTCCCGCCTGAACCCTATAAATACAACTTTGCTAAAGATGGCGGACTGTGGGGGACTGCCCCAGGTAGTTCAGCCTGGGAAGCTCACCGAGGCCTTCAAGTACTTTTTGCAGGGAATGGGCTACGTCCCGTCTGCCAGCATGACTCGGCTCGCCCGATCACGAACCCACTCAACCTCGAGTAGCCTCGGCTCTGGAGAAAGTCCCTTCAGCCGGTCTGTCACCAGCAATCAGTCAGATGGAACTCAAGAATCCTGTGAGTCCCCTGATGTCCTGGACAGACACCAGACCATGGAGGTGTCCTGCTAAGCAGATGCTCCTCCCCTGGACCATTGCAAGTCCATCCTTCAAATGACCACTCCATAATATAACATTTCATORF Start: ATG at 71ORF Stop: TAA at 1160SEQ ID NO: 254363 aaMW at 39967.8 kDNOV89c,MDELQDVQLTEIKPLLNDKEHDIETTHGVVHVTIRGLPKGNRPVILTYHDIGLNHKSCCG56870-03 Protein SequenceFNAFFNFEDMQEITQHFAVCHVDAPGQQEGAPSFPTGYQYPTMDELAEMLPPVLTHLSLKSEEGIGVGAGAYILSRFALNHPELVEGLVLINVDPCAKGWIDWAASKLSGLTTNVVDIILAHHFGQEELQANLDLIQTYRMHIAQDINQDNLQLFLNSYNGRRDLEIERPILGQNDNKSKTLKCSTLLVVGDNSPAVEAVVECNSRLNPINTTLLKMADCGGLPQVVQPGKLTEAFKYFLQGMGYVPSASMTRLARSRTHSTSSSLGSGESPFSRSVTSNQSDGTQESCESPDVLDRHQTMEVSCSEQ ID NO: 2551220 bpNOV89d,ACTTCTTTCTTTTCTGTTTCAGAGTTACTGATTTATTCTTGAGATTCCTCTACTCTCGCG56870-04DNA SequenceTTATCTGACCTCATGGATGAACTTCAGGATGTTCAGCTCACAGAGATCAAACCACTTCTAAATGATAAGAATGGTACAAGAAACTTCCAGGACTTTGACTGTCAGGAACATGATATAGAAACAACTCATGGTGTGGTCCACGTCACTATAAGAGGCTTACCCAAAGGAAACAGACCAGTTATACTAACATATCATGACATTGGCCTCAACCGTAAATCCTGTTTCAATGCATTCTTTAACTTTGAGGATATGCAAGAGATCACCCAGCACTTTGCTGTCTGTCATGTGGATGCCCCAGGCCAGCAGGAAGGTGCACCCTCTTTCCCAACAGGGTATCAGTACCCCACAATGGATGAGCTGGCTGAAATGCTGCCTCCTGTTCTTACCCACCTAAGCCTGAAAAGCATCATTGGAATTGGAGTTGGAGCTGGAGCTTACATCCTCAGCAGATTTGCACTCAACCATCCAGAGCTTGTGGAAGGCCTTGTGCTCATTAATGTTGACCCTTGCGCTAAAGGCTGGATTGACTGGGCAGCTTCCAAACTCTCTGGCCTGACAACCAATGTTGTGGACATTATTTTGGCTCATCACTTTGGGCAGGAAGAGTTACAGGCCAACCTGGACCTGATCCAAACCTACAGAATGCATATTGCCCAAGACATCAACCAAGACAACCTGCAGCTCTTCTTGAATTCCTACAATGGACGCAGAGACCTGGAGATCGAAAGACCCATACTGGGCCAAAATGATAACAAATCAAAAACATTAAAGTGTTCTACTTTACTGGTGGTAGGGGACAATTCGCCTGCAGTTGAGGCTGTGATGGCGGACTGTGGGGGACTGCCCCAGGTAGTTCAGCCTGGGAAGTTCACCGAGGCCTTCAAGTACTTTTTGCAGGGAATGGGCTACACACCATCTGCCAGCATGACTCGGCTCGCCCGATCACGAACCCACTCAACCTCGAGTAGCCTCGGCTCTGGAGAAAGTCCCTTCAGCCGGTCTGTCACCAGCAATCAGTCAGATGGAACTCAAGAATCCTGTGAGTCCCCTGATGTCCTGGACAGACACCAGACCATGGAGGTGTCCTGCTAAGCAGATGCTCCTCCCCTGGACCATTGCAAGTCCATCCTTCAAATGACCACTCCATAATATAACATTTCATORF Start: ATG at 71ORF Stop: TAA at 1148SEQ ID NO: 256359 aaMW at 39652.2 kDNOV89d,MDELQDVQLTEIKPLLNDKNGTRNFQDFDCQEHDIETTHGVVHVTIRGLPKGNRPVILCG56870-04 Protein SequenceTYHDIGLNRKSCFNAFFNFEDMQEITQHFAVCHVDAPGQQEGAPSFPTGYQYPTMDELAEMLPPVLTHLSLKSIIGIGVGAGAYILSRFALNHPELVEGLVLINVDPCAKGWIDWAASKLSGLTTNVVDIILAHHFGQEELQANLDLIQTYRMHIAQDINQDNLQLFLNSYNGRRDLEIERPILGQNDNKSKTLKCSTLLVVGDNSPAVEAVMADCGGLPQVVQPGKFTEAFKYFLQGMGYTPSASMTRLARSRTHSTSSSLGSGESPFSRSVTSNQSDGTQESCESPDVLDRHQTMEVSCSEQ ID NO: 257970 bpNOV89e,ATGGATGAACTTCAGGATGTTCAGCTCACAGAGATCAAACCACTTCTAAATGATAAGACG56870-05 DNA SequenceATGGTACAAGAAACTTCCAGGACTTTGACTGTCAGTATCAGTACCCCACAATGGATGAGCTGGCTGAAATGCTGCCTCCTGTTCTTACCCACCTAAGCCTGAAAAGCATCATTGGAATTGGAGTTGGAGCTGGAGCTTACATCCTCAGCAGATTTGCACTCAACCATCCAGAGCTTGTGGAAGGCCTTGTGCTCATTAATGTTGACCCTTGCGCTAAAGGCTGGATTGACTGGGCAGCTTCCAAACTCTCTGGCCTGACAACCAATGTTGTGGACATTATTTTGGCTCATCACTTTGGGCAGGAAGAGTTACAGGCCAACCTGGACCTGATCCAAACCTACAGAATGCATATTGCCCAAGACATCAACCAAGACAACCTGCAGCTCTTCTTGAATTCCTACAATGGGCGCAGAGACCTGGAGATCGAAAGACCCATACTGGGCCAAAATGATAACAAATCAAAAACATTAAAGTGTTCTACTTTACTGGTGGTAGGGGACAATTCGCCTGCAGTTGAGGCTGTGGTCGAATGCAATTCCCGCCTGAACCCTATAAATACAACTTTGCTAAAGATGGCGGACTGTGGGGGACTGCCCCAGGTAGTTCAGCCTGGGAAGCTCACCGAGGCCTTCAAGTACTTTTTGCAGGGAATGGGCTACGTCCCGTCTGCCAGCATGACTCGGCTCGCCCGATCACGAACCCACTCAACCTCGAGTAGCCTCGGCTCTGGAGAAAGTCCCTTCAGCCGGTCTGTCACCAGCAATCAGTCAGATGGAACTCAAGAATCCTGTGAGTCCCCTGATGTCCTGGACAGACACCAGACCATGGAGGTGTCCTGCTAAGCAGATGCTCCTCCCCTGGACCATTGCAAGTCCATCCTTCAAATGACCACTCCATAATATAACATTTCATORF Start: ATG at 1ORF Stop: TAA at 898SEQ ID NO: 258299 aaMW at 32956.9 kDNOV89e,MDELQDVQLTEIKPLLNDKNGTRNFQDFDCQYQYPTMDELAEMLPPVLTHLSLKSIIGCG56870-05 Protein SequenceIGVGAGAYILSRFALNHPELVEGLVLINVDPCAKGWIDWAASKLSGLTTNVVDIILAHHFGQEELQANLDLIQTYRMHIAQDINQDNLQLFLNSYNGRRDLEIERPILGQNDNKSKTLKCSTLLVVGDNSPAVEAVVECNSRLNPINTTLLKMADCGGLPQVVQPGKLTEAFKYFLQGMGYVPSASMTRLARSRTHSTSSSLGSGESPFSRSVTSNQSDGTQESCESPDVLD


[0791] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 89B.
467TABLE 89BComparison of NOV89a against NOV89b through NOV89e.Identities/ProteinNOV89a Residues/Similarities forSequenceMatch Residuesthe Matched RegionNOV89b 1 . . . 375336/375 (89%) 1 . . . 375338/375 (89%)NOV89c 1 . . . 375326/375 (86%) 1 . . . 363326/375 (86%)NOV89d 1 . . . 375321/375 (85%) 1 . . . 359321/375 (85%)NOV89e104 . . . 375233/272 (85%) 28 . . . 299233/272 (85%)


[0792] Further analysis of the NOV89a protein yielded the following properties shown in Table 89C.
468TABLE 89CProtein Sequence Properties NOV89aPSort0.4500 probability located in cytoplasm; 0.3000 probabilityanalysis:located in microbody (peroxisome); 0.1685 probability locatedin lysosome (lumen); 0.1000 probability located inmitochondrial matrix spaceSignalPNo Known Signal Sequence Predictedanalysis:


[0793] A search of the NOV89a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 89D.
469TABLE 89DGeneseq Results for NOV89aNOV89aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAM94019Human stomach cancer expressed 1 . . . 375360/375 (96%)0.0polypeptide SEQ ID NO 108- 1 . . . 363361/375 (96%)Homo sapiens, 363 aa.[WO200109317-A1, 8 FEB. 2001]AAG64392Human reducing agent and 1 . . . 375360/375 (96%)0.0tunicamycin-responsive protein 40- 1 . . . 363361/375 (96%)Homo sapiens, 363 aa.[WO200155375-A1,2 AUG. 2001]AAB94494Human protein sequence SEQ ID 1 . . . 375360/375 (96%)NO: 15186-Homo sapiens, 363 aa. 1 . . . 363361/375 (96%)[EP1074617-A2, 7 FEB. 2001]AAU31598Novel human secreted protein 68 . . . 374282/323 (87%)e−154#2089-Homo sapiens, 395 aa. 1 . . . 307286/323 (88%)[WO200179449-A2,25 OCT. 2001]AAB95462Human protein sequence SEQ ID133 . . . 375240/243 (98%)e−138NO: 17944-Homo sapiens, 286 aa. 44 . . . 286242/243 (98%)[EP1074617-A2, 7 FEB. 2001]


[0794] In a BLAST search of public sequence databases, the NOV89a protein was found to have homology to the proteins shown in the BLASTP data in Table 89E.
470TABLE 89EPublic BLASTP Results for NOV89aNOV89aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumerProtein/Organism/LengthResiduesthe Matched PortionValueQ9UGV2NDRG3 protein-Homo sapiens1 . . . 375373/375 (99%)0.0(Human), 375 aa.1 . . . 375374/375 (99%)Q96PL8NDR1-RELATED1 . . . 375372/375 (99%)0.0DEVELOPMENT PROTEIN NDR3-1 . . . 375373/375 (99%)Homo sapiens (Human), 375 aa.Q9QYF9NDRG3 protein (Ndr3 protein)-1 . . . 375358/375 (95%)0.0Mus musculus (Mouse), 375 aa.1 . . . 375368/375 (97%)AAH18504SIMILAR TO N-MYC1 . . . 375359/388 (92%)0.0DOWNSTREAM REGULATED 3-1 . . . 388368/388 (94%)Mus musculus (Mouse), 388 aa.Q96SM2CDNA FLJ14759 FIS, CLONE1 . . . 375360/375 (96%)0.0NT2RP3003290, MODERATELY1 . . .363361/375 (96%)SIMILAR TO MUS MUSCULUSNDR1 RELATED PROTEIN NDR3-Homo sapiens (Human), 363 aa.


[0795] PFam analysis predicts that the NOV89a protein contains the domains shown in the Table 89F.
471TABLE 89FDomain Analysis of NOV89aIdentities/PfamNOV89aSimilarities forExpectDomainMatch Regionthe Matched RegionValueOrn_Arg_deC_N:62 . . . 89 7/33 (21%)1.9domain 1 of 1 24/33 (73%)abhydrolase:87 . . . 310 48/239 (20%)0.0066domain 1 of 1142/239 (59%)Ndr: domain 1 of 122 . . . 346210/340 (62%)3.7e−211311/340 (91%)



Example 90

[0796] The NOV90 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 90A.
472TABLE 90ANOV90 Sequence AnalysisSEQ ID NO: 259632 bpNOV90a,GAAACTATAAAGGGTCCGAACCCTCTTTTAAAGGATCCCAATGCATTTCTTTGATCCCCG59764-01 DNA SequenceTCGCCGGTGCGACGGTACCACCATCCCAGCTGTGAGGCTGCCATCAACACCCACATCAGCCTGGAGCTCCACGCATCCTATGTGTACCTGTCCATGGCCTTCTACTTCGACCAGGACGACGCGGCCCTGGAGCACTTTGACCGCTACTTCCTGCGCCAGTCGCAGGAGAAAAGGGAGCACGCCCAGGAGCTGATGAGCCTGCAGAACCTGCGCGGTGGCCGCATCTGCCTTCATGACATCAGGAAGCCAGAGGGCCAAGGCTGGGAGAGCGGGCTCAAGGCCATGGAGTGCACCTTCCACCTGGAGAAGAACATCAACCAGAGCCTCCTGGAGCTGCACCAGCTGGCCAGGGAGAACGGCGACCCCCAGCTCTGCGACTTCCTGGAGAACGACTTCCTGAACCAGCAGGCCAAGACCATCAAAGAGCTGGGTGGCTACCTGAGCAACCTGCACAAGATGGGGGCCCCGGAAGCAGGCCTGGCAGAGTACCTCTTTAACAAGCTCACCCTGGGCCGCAGCGAACCACTTCCTTGAACCAGCAGGCCAAGACCATCAAAGAGATTGGTGGCTACCTORF Start: ATG at 41ORF Stop: TGA at 590SEQ ID NO: 260183 aaMW at 21159.6 kDNOV90a,MHFFDPSPVRRYHHPSCEAAINTHISLELHASYVYLSMAFYFDQDDAALEHFDRYFLRCG59764-01 Protein SequenceQSQEKREHAQELMSLQNLRGGRICLHDIRKPEGQGWESGLKAMECTFHLEKNINQSLLELHQLARENGDPQLCDFLENDFLNQQAKTIKELGGYLSNLHKMGAPEAGLAEYLFNKLTLGRSEPLP


[0797] Further analysis of the NOV90a protein yielded the following properties shown in Table 90B.
473TABLE 90BProtein Sequence Properties NOV90aPSort0.4500 probability located in cytoplasm; 0.1400 probabilityanalysis:located in microbody (peroxisome); 0.1000 probability locatedin mitochondrial matrix space; 0.1000 probability located inlysosome (lumen)SignalPNo Known Signal Sequence Predictedanalysis:


[0798] A search of the NOV90a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 90C.
474TABLE 90CGeneseq Results for NOV90aNOV90aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAU07889Polypeptide sequence for human 7 . . . 180159/174 (91%)4e−91hspG34a-Homo sapiens, 221 aa.45 . . . 218164/174 (93%)[WO200166752-A2,13 SEP. 2001]AAU07890Polypeptide sequence for human 6 . . . 177125/172 (72%)6e−70hspG34b-Homo sapiens, 183 aa. 6 . . . 177149/172 (85%)[WO200166752-A2,13 SEP. 2001]AAB90804Human shear stress-response 7 . . . 180114/174 (65%)6e−64protein SEQ ID NO: 108-Homo 7 . . . 180141/174 (80%)sapiens, 183 aa. [WO200125427-A1, 12 APR. 2001]AAR71567Human monocyte growth factor- 7 . . . 180114/174 (65%)6e−64Homo sapiens, 183 aa. 7 . . . 180141/174 (80%)[JP07031482-A, 3 FEB. 1995]AAU27741Mouse full-length polypeptide 6 . . . 180112/175 (64%)5e−63sequence #66-Mus musculus, 182 6 . . . 180141/175 (80%)aa. [WO200164834-A2,7 SEP. 2001]


[0799] In a BLAST search of public sequence databases, the NOV90a protein was found to have homology to the proteins shown in the BLASTP data in Table 90D.
475TABLE 90DPublic BLASTP Results for NOV90aNOV90aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueQ9BXU8Ferritin heavy polypeptide-like 17- 6 . . . 177125/172 (72%)2e−69Homo sapiens (Human), 183 aa. 6 . . . 177149/172 (85%)P29389Ferritin heavy chain (Ferritin H 6 . . . 180115/175 (65%)6e−64subunit)-Cricetulus griseus10 . . . 184142/175 (80%)(Chinese hamster), 185 aa.A26886ferritin heavy chain-chicken, 180 6 . . . 180112/175 (64%)1e−63aa. 5 . . . 179142/175 (81%)P08267Ferritin heavy chain (Ferritin H 6 . . . 180112/175 (64%)1e−63subunit)-Gallus gallus (Chicken), 4 . . . 178142/175 (81%)179 aa.Q95MP7FERRITIN-Canis familiaris 6 . . . 180112/175 (64%)2e−63(Dog), 183 aa. 6 . . . 180143/175 (81%)


[0800] PFam analysis predicts that the NOV90a protein contains the domains shown in the Table 90E.
476TABLE 90EDomain Analysis of NOV90aIdentities/PfamNOV90aSimilarities forExpectDomainMatch Regionthe Matched RegionValueBacteriofer:14 . . . 159 35/172 (20%)6.7domain 1 of 1 76/172 (44%)ferritin:17 . . . 173 92/161 (57%)4.7e−87domain 1 of 1138/161 (86%)



Example 91

[0801] The NOV91 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 91A.
477TABLE 91ANOV91 Sequence AnalysisSEQ ID NO: 261487 bpNOV91a,TGCTGTGCGTTGTCTTTCCTTCTCACTCAAGCCTGTGAAATCTCTCTTTCAGGTTGACCG59710-01 DNA SequenceAGACTAATGGAGTTGCATTTTAAATATCTGGGTGCAATGCAGGTGGCGGACAAGAAGATTGAAGGGGAAAAACACGACATGGTCCGGCGAGGAGAGATCATCGACAATGACACCGAGGAGGAGTTCTACCTCCGGCGCCTGGATGCGGGGCTCTTTGTTCTCCAGCACATCTGCTACATCATGGCCGAGATCTGCAATGCCAATGTCCCCCAGATTCGCCAGAGGGTTCACCAGATCCTAAACATGCGAGGAAGCTCCATCAAAATTGTCAGGCATATCATCAAGGAGTATGCAGAGAACATCGGGGACGGCCGGAGCCCGGAGTTCCGGGAGAACGAGCAAAAGCGCATCCTGGGCTTGCTGGAGAACTTCTAGAGGCACCTTGGCCCTGCGCATCATGGACTCTCTCAGCTTCCCTCCCAGGATCAGORF Start: ATG at 65ORF Stop: TAG at 431SEQ ID NO: 262122 aaMW at 14385.4 kDNOV91a,MELHFKYLGAMQVADKKIEGEKHDMVRRGEIIDNDTEEEFYLRRLDAGLFVLQHICYICG59710-01 Protein SequenceMAEICNANVPQIRQRVHQILNMRGSSIKIVRHIIKEYAENIGDGRSPEFRENEQKRILGLLENF


[0802] Further analysis of the NOV91a protein yielded the following properties shown in Table 91B.
478TABLE 91BProtein Sequence Properties NOV91aPSort0.6500 probability located in cytoplasm; 0.1000 probabilityanalysis:located in mitochondrial matrix space; 0.1000 probabilitylocated in lysosome (lumen); 0.0000 probability located inendoplasmic reticulum (membrane)SignalPNo Known Signal Sequence Predictedanalysis:


[0803] A search of the NOV91a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 91C.
479TABLE 91CGeneseq Results for NOV91aNOV91aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAU28058Novel human secretory protein, 1 . . . 122122/122 (100%)1e−66Seq ID No 227-Homo sapiens,397 . . . 518122/122 (100%)518 aa. [WO200166689-A2,13 SEP. 2001]AAM93729Human polypeptide, SEQ ID NO: 1 . . . 122122/122 (100%)1e−663689-Homo sapiens, 563 aa.442 . . . 563122/122 (100%)[EP1130094-A2, 5 SEP. 2001]AAB63116Human secreted protein sequence 1 . . . 119119/119 (100%)1e−64encoded by gene 39 SEQ ID283 . . . 401119/119 (100%)NO: 126 -Homo sapiens, 401 aa.[WO200061748-A1,19 OCT. 2000]AAU28246Novel human secretory protein, 1 . . . 118104/120 (86%)2e−51Seq ID No 603-Homo sapiens,197 . . . 316106/120 (87%)360 aa. [WO200166689-A2,13 SEP. 2001]ABB21673Protein #3672 encoded by probe 24 . . . 55 32/32 (100%)1e−11for measuring heart cell gene 1 . . . 132 32/32 (100%)expression-Homo sapiens, 32 aa.[WO200157274-A2,9 AUG. 2001]


[0804] In a BLAST search of public sequence databases, the NOV91a protein was found to have homology to the proteins shown in the BLASTP data in Table 91D.
480TABLE 91DPublic BLASTP Results for NOV91aNOV91aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumerProtein/Organism/LengthResiduesthe Matched PortionValueQ96KD2TESTES DEVELOPMENT- 1 . . . 122122/122 (100%)5e−66RELATED NYD-SP19-Homo255 . . . 376122/122 (100%)sapiens (Human), 376 aa.Q9H7A5CDNA: FLJ21108 FIS, CLONE 1 . . . 122121/122 (99%)5e−65CAS05257-Homo sapiens104 . . . 225121/122 (99%)(Human), 225 aa.O62703P14-Bos taurus (Bovine), 122 aa. 1 . . . 122116/122 (95%)2e−62 1 . . . 122119/122 (97%)Q9CWL85730471K09RIK PROTEIN-Mus 1 . . . 122115/122 (94%)3e−62musculus (Mouse), 563 aa.442 . . . 563118/122 (96%)Q9Y3M7DJ633O20.1 (P14L, SIMILAR TO 1 . . . 93 93/93 (100%)3e−48BOS TAURUS P14)-Homo192 . . . 284 93/93 (100%)sapiens (Human), 284 aa(fragment).


[0805] PFam analysis predicts that the NOV91a protein contains the domains shown in the Table 91E.
481TABLE 91EDomain Analysis of NOV91aIdentities/PfamNOV91aSimilarities forExpectDomainMatch Regionthe Matched RegionValueNo Significant Matches Found



Example 92

[0806] The NOV92 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 92A.
482TABLE 92ANOV92 Sequence AnalysisSEQ ID NO:2636527 bpNOV92a,CCACAGAGGGGAAATGCCAGCTTCCCTCTCCCTGGGGCTCCGTGCCCCCTCTGATCCACG59754-02 DNA SequenceGCCCTTCGAATTCCCACCCGCCTCCATCGGCCAGCTGCTCTACATTCCCTGTGTGGTGTCCTCGGGGGACATGCCCATCCGTATCACCTGGAGGAAGGACGGACAGGTGATCATCTCAGGCTCGGGCGTGACCATCGAGAGCAAGGAATTCATGAGCTCCCTGCAGATCTCTAGCGTCTCCCTCAAGCACAACGGCAACTATACATGCATCGCCAGCAACGCAGCCGCCACCGTGAGCATTGTGTCTCCAGAACACAGGTTTTTTATTACCTACCACGGCGGGCTGTACATCTCTGACGTACAGAAGGAGGACGCCCTCTCCACCTATCGCTGCATCACCAAGCACAAGTATAGCGGGGAGACCCGGCAGAGCAATGGGGCACGCCTCTCTGTGACAGACCCTGCTGAGTCGATCCCCACCATCCTGGATGGCTTCCACTCCCAGGAAGTGTGGGCCGGCCACACCGTGGAGCTGCCCTGCACCGCCTCGGGCTACCCTATCCCCGCCATCCGCTGGCTCAAGGATGGCCGGCCCCTCCCGGCTGACAGCCGCTGGACCAAGCGCATCACAGGGCTGACCATCAGCGACTTGCGGACCGAGGACAGCGGCACCTACATTTGTGAGGTCACCAACACCTTCGGTTCGGCAGAGGCCACAGGCATCCTCATGGTCATTGATCCCCTTCATGTGACCCTGACACCAAAGAAGCTGAAGACCGGCATTGGCAGCACGGTCATCCTCTCCTGTGCCCTGACGGGCTCCCCAGAGTTCACCATCCGCTGGTATCGCAACACGGAGCTGGTGCTGCCTGACGAGGCCATCTCCATCCGCGGGCTCAGCAACGAGACGCTGCTCATCACCTCGGCCCAGAAGAGCCATTCCGGGGCCTACCAGTGCTTCGCTACCCGCAAGGCCCAGACCGCCCAGGACTTTGCCATCATTGCACTTGAGGATGGCACGCCCCGCATCGTCTCGTCCTTCAGCGAGAAGGTGGTCAACCCCGGGGAGCAGTTCTCACTGATGTGTGCGGCCAAGGGCGCCCCGCCCCCCACGGTCACCTGGGCCCTCGACGATGAGCCCATCGTGCGGGATGGCAGCCACCGCACCAACCAGTACACCATGTCGGACGGCACCACCATCAGCCACATGAACGTCACAGGCCCCCAGATCCGCGACGGGGGCGTGTACCGGTGCACAGCGCGGAACTTGGTGGGCAGTGCTGAATATCAGGCGCGAATAAACGTAAGAGGCCCACCCAGCATCCGGGCTATGCGGAACATCACAGCAGTCGCCGGGCGGGACACCCTTATCAACTGCAGGGTCATCGGCTATCCCTACTACTCCATCAAGTGGTACAAGGATGCCTTGCTGCTGCCAGACAACCACCGCCAGGTGGTGTTTGAGAATGGGACCCTCAAGCTGACTGACGTGCAGAAGGGCATGGATGAGGGGGAGTACCTGTGCAGTGTCCTCATCCAGCCCCAGCTCTCCATCAGCCAGAGCGTTCACGTAGCCGTCAAAGTGCCCCCTCTGATCCAGCCCTTCGAATTCCCACCCGCCTCCATCGGCCAGCTGCTCTACATTCCCTGTGTGGTGTCCTCGGGGGACATGCCCATCCGTATCACCTGGAGGAAGGACGGACAGGTGATCATCTCAGGCTCGGGCGTGACCATCGAGAGCAAGGAATTCATGAGCTCCCTGCAGATCTCTAGCGTCTCCCTCAAGCACAACGGCAACTATACATGCATCGCCAGCAACGCAGCCGCCACCGTGAGCCGGGAGCGTCAGCTCATCGTGCGTGTGCCCCCTCGATTTGTGGTGCAACCCAACAACCAGGATGGCATCTACGGCAAAGCTGGTGTGCTCAACTGCTCGGTGGACGGCTACCCCCCACCCAAGGTCATGTGGAAGCATGCCAAGGGGAGCGGGAACCCCCAGCAGTACCACCCTGTGCCCCTCACTGGCCGCATCCAGATCCTGCCCAACAGCTCGCTGCTGATCCGCCACGTCCTAGAAGAGGACATCGGCTACTACCTCTGCCAGGCCAGCAACGGCGTAGGCACCGACATCAGCAAGTCCATGTTCCTCACAGTCAAGATCCCGGCCATGATCACTTCCCACCCCAACACCACCATCGCCATCAAGGGCCATGCGAAGGAGCTAAACTGCACGGCACGGGGTGAGCGGCCCATCATCATCCGCTGGGAGAAGGGGGACACAGTCATCGACCCTGACCGCGTCATGCGGTATGCCATCGCCACCAAGGACAACGGCGACGAGGTCGTCTCCACACTGAAGCTCAAGCCCGCTGACCGTGGGGACTCTGTGTTCTTCAGCTGCCATGCCATCAACTCGTATGGGGAGGACCGGGGCTTGATCCAACTCACTGTGCAAGAGCCCCCCGACCCCCCAGAGCTGGAGATCCGGGAGGTGAAGGCCCGGAGCATGAACCTGCGCTGGACCCAGCGATTCGACGGGAACAGCATCATCACGGGCTTCGACATTGAATACAAGAACAAATCAGATTCCTGGGACTTCAAGCAGTCCACACGCAACATCTCCCCCACCATCAACCAGGCCAACATTGTGGACTTGCACCCGGCATCTGTGTACAGCATCCGCATGTACTCTTTCAACAAGATTGGCCGCAGTGAACCAAGCAAGGAGCTCACCATCAGCACTGAGGAGGCCGCTCCCGATGGGCCCCCCATGGATGTTACCTTGCAGCCAGTGACCTCACAGAGCATCCAGGTGACCTGGAAGGCACCCAAGAAGGAGCTGCAGAACGGTGTCATCCGGGGCTACCAGATTGGCTACAGAGAGAACAGCCCCGGCAGCAACGGGCAGTACAGCATCGTGGAGATGAAGGCCACGGGGGACAGCGAGGTCTACACCCTGGACAACCTCAAGAAGTTCGCCCAGTATGGGGTGGTGGTCCAAGCCTTCAATCGGGCTGGCACGGGGCCCTCTTCCAGCGAGATCAATGCCACCACTCTGGAGGATGTGCCCAGCCAGCCCCCTGAGAACGTCCGGGCCCTGTCCATCACTTCTGACGTGGCCGTCATCTCCTGGTCAGAGCCCCCGCGCAGCACCCTCAATGGCGTCCTCAAAGGCTATCGGGTCATCTTCTGGTCCCTCTATGTTGATGGGGAGTGGGGCGAGATGCAGAACATCACCACCACGCGGGAGCGGGTGGAGCTGCGGGGCATGGAGAAGTTCACCAACTACAGCGTCCAGGTGCTGGCCTACACCCAGGCTGGGGACGGCGTACGCAGCAGTGTGCTCTACATCCAGACCAAGGAGGACGTTCCAGGTCCCCCTGCTGGCATCAAAGCTGTCCCTTCATCAGCTAGCAGTGTGGTTGTGTCTTGGCTCCCCCCTACCAAGCCCAACGGGGTGATCCGCAAGTACACCATCTTCTGTTCCAGCCCCGGGTCTGGCCAGCCGGCTCCCAGCGAGTACGAGACGAGTCCAGAGCAGCTCTTCTACCGGATCGCCCACCTAAACCGCGGTCAGCAGTATCTGCTGTGGGTGGCCGCCGTCACCTCTGCCGGCCGGGGCAACAGCAGCGAGAAGGTGACCATCGAGCCTGCTGGCAAGGCCCCAGCAAAGATCATCTCCTTTGGGGGCACCGTGACAACACCTTGGATGAAAGATGTTCGGCTGCCTTGCAATTCAGTGGGAGATCCAGCCCCTGCTGTGAAGTGGACCAAGGACAGTGAAGACTCGGCCATTCCAGTGTCCATGGATGGGCACCGGCTCATCCACACCAATGGCACACTGCTGCTGCGTGCAGTGAAGGCTGAGGACTCTGGCTACTACACGTGCACGGCCACCAACACTGGTGGCTTTGACACCATCATCGTCAACCTTCTGGTGCAAGTTCCCCCGGACCAGCCCCGCCTCACTGTCTCCAAAACCTCAGCTTCGTCCATCACCCTGACCTGGATTCCAGGTGACAATGGGGGCAGCTCCATCCGAGGCTTCGTGCTACAGTACTCGGTGGACAACAGCGAGGAGTGGAAGGATGTGTTCATCAGCTCCAGCGAGCGCTCCTTCAAGCTGGACAGCCTCAAGTGTGGCACGTGGTACAAGGTGAAGCTGGCAGCCAAGAACAGCGTGGGCTCTGGGCGCATCAGCGAGATCATCGAGGCCAAGACCCACGGGCGGGAGCCCTCCTTCAGCAAAGACCAACACCTCTTCACCCACATCAACTCCACGCATGCTCGGCTTAACCTGCAGGGCTGGAACAATGGGGGCTGCCCTATCACAGCCATCGTTCTGGAGTACCGGCCCAAGGGGACCTGGGCCTGGCAGGGCCTCCGGGCCAACAGCTCCGGGGAGGTGTTTCTGACGGAACTGCGAGAGGCCACGTGGTACGAGCTGCGCATGAGGGCTTGCAACAGTGCGGGCTGCGGCAATGAAACAGCCCAGTTCGCCACCCTGGACTACGATGGCAGCACCATTCCACCCATCAAGTCTGCTCAAGGTGAAGGGGATGATGTGAAGAAGCTGTTCACCATCGGCTGCCCTGTCATCCTGGCCACACTGGGGGTGGCACTGCTCTTCATCGTACGCAAGAAGAGGAAGGAGAAACGGCTGAAGCGACTCCGAGATGCAAAGAGTTTGGCAGAAATGTTGATAAGCAAGAACAATAGAAGCTTTGACACCCCTGTGAAAGGGCCACCCCAGGGCCCACGGCTACACATTGACATCCCCAGGGTCCAGCTGCTCATCGAGGACAAAGAAGGCATCCTGTCAACCCACAGAGCTTCTGTACTGGCGTCTCCTTGCACCACCCAACCCTCATCCAGAGCACAGGACCCCTCATCGACATGTCTGACATCCGGCCAGGAACCAATCCAGTGTCCAGGAAGAATGTGAAGTCAGCCCACAGCACCCGGAACCGGTACTCAAGCCAGTGGACCCTGACCAAGTGCCAGGCCTCCACACCTGCCCGCACCCTCACCTCCGACTGGCGCACCGTGGGCTCCCAGCATGGTGTCACGGTCACTGAGAGTGACAGCTACAGTGCCAGCCTGTCCCAGGACACAGACAAAGGAAGGAACAGCATGGTGTCCACTGAGAGTGCCTCTTCCACCTACGAGGAGCTGGCCCGGGCCTATGAGCATGCCAAGCTGGAGGAGCAGCTGCAGCACGCCAAGTTTGAGATCACCGAGTGCTTCATCTCTGACAGTTCCTCTGACCAGATGACCACAGGCACCAACGAGAACGCCGACAGCATGACATCCATGAGCACACCCTCAGAGCCTGGCATCTGCCGCTTTACCGCCTCACCACCCAAGCCCCAGGATGCGGACCGGGGCAAAAACGTGGCTGTGCCCATCCCTCACCGGGCCAACAAGAGTGACTACTGCAACCTGCCCCTGTATGCCAAGTCAGAGGCCTTCTTTCGAAAGGCAGATGGACGTGAGCCCTGCCCCGTGGTCCCACCCCGTGAGGCCTCCATCCGGAACCTGGCTCGAACCTACCACACCCAGGCTCGCCACCTGACCCTGGACCCTGCCAGCAAGTCCTTGGGCCTTCCCCACCCAGGGGCCCCCGCTGCCGCCTCCACAGCCACCTTACCTCAGAGGACTCTGGCCATGCCAGCCCCCCCAGCCGGCACAGCCCCCCCAGCCCCCGGCCCCACCCCTGCTGAGCCACCCACCGCCCCCAGCGCTGCCCCTCCGGCCCCCAGCACCGAGCCTCCACGAGCCGGGGGCCCACACACCAAAATGGGGGGCTCCAGGGACTCGCTTCTCGAGATGAGCACATCGGGGGTAGGGAGGTCTCAGAAGCAGGGGGCCGGGGCCTACTCCAAATCCTACACCCTGGTGTAGGGCCGGCAGGAAGAGCAGCCACGCCTGGGCCGCGCCGCGCCGCAGCCCCACACGCCAGCTCGGCTGTTTTTCTGCATTATTTATATTCAACTGACAGACAAAAACCAACCAACGACAAAACAAAAACCCCCAATCATGAACGCCTGTACATAGAACTCTTTTGTACAAATGAAACTATTTTCTTCTTCTCCATGAAGCCAGGGCACAAAGAATTTGACAGTACAAGTCAAATCCCCCACCCCACAAAATATGTGTGGAGATATATATACATATATAGACAGACAGGAACGCCTCCACGAGCTATATATCTATATATTTCTCTCACCCTATTTTGAGACAGAGGCACAAAGACTCAGCAATTTTTTTCCCTCCTCCTCACCTTCCCCCCAGTCTAGGTGGTTTTGACAAAGACCAAAATCCCAACTCAGAGACACTGCATGCGATTTTACTGTTCCAAGAAAACCAGGAGTTGCTTCAATTTGCAGATGCTTATGTGTTAATACCTTTTTCTATGAAAAAAGACCCAGCGCCGTGTGCAATAAAGGTTATGTTTCCAAAAAAAAGCTTORF Start: ATG at 129ORF Stop: TAG at 5958SEQ ID NO:2641943 aaMW at 211904.3 kDNOV92a,MPIRITWRKDGQVIISGSGVTIESKEFMSSLQISSVSLKHNGNYTCIASNAAATVSIVCG59754-02 ProteinSequenceSPEHRFFITYHGGLYISDVQKEDALSTYRCITKHKYSGETRQSNGARLSVTDPAESIPTILDGFHSQEVWAGHTVELPCTASGYPIPAIRWLKDGRPLPADSRWTKRITGLTISDLRTEDSGTYICEVTNTFGSAEATGILMVIDPLHVTLTPKKLKTGIGSTVILSCALTGSPEFTIRWYRNTELVLPDEAISIRGLSNETLLITSAQKSHSGAYQCFATRKAQTAQDFAIIALEDGTPRIVSSFSEKVVNPGEQFSLMCAAKGAPPPTVTWALDDEPIVRDGSHRTNQYTMSDGTTISHMNVTGPQIRDGGVYRCTARNLVGSAEYQARINVRGPPSIRAMRNITAVAGRDTLINCRVIGYPYYSIKWYKDALLLPDNHRQVVFENGTLKLTDVQKGMDEGEYLCSVLIQPQLSISQSVHVAVKVPPLIQPFEFPPASIGQLLYIPCVVSSGDMPIRITWRKDGQVIISGSGVTIESKEFMSSLQISSVSLKHNGNYTCIASNAAATVSRERQLIVRVPPRFVVQPNNQDGIYGKAGVLNCSVDGYPPPKVMWKHAKGSGNPQQYHPVPLTGRIQILPNSSLLIRHVLEEDIGYYLCQASNGVGTDISKSMFLTVKIPAMITSHPNTTIAIKGHAKELNCTARGERPIIIRWEKGDTVIDPDRVMRYAIATKDNGDEVVSTLKLKPADRGDSVFFSCHAINSYGEDRGLIQLTVQEPPDPPELEIREVKARSMNLRWTQRFDGNSIITGFDIEYKNKSDSWDFKQSTRNISPTINQANIVDLHPASVYSIRMYSFNKIGRSEPSKELTISTEEAAPDGPPMDVTLQPVTSQSIQVTWKAPKKELQNGVIRGYQIGYRENSPGSNGQYSIVEMKATGDSEVYTLDNLKKFAQYGVVVQAFNRAGTGPSSSEINAEELEDVPSQPPENVRALSITSDVAVISWSEPPRSTLNGVLKGYRVIFWSLYVDGEWGEMQNITTTRERVELRGMEKFTNYSVQVLAYTQAGDGVRSSVLYIQTKEDVPGPPAGIKAVPSSASSVVVSWLPPTKPNGVIRKYTIFCSSPGSGQPAPSEYETSPEQLFYRIAHLNRGQQYLLWVAAVTSAGRGNSSEKVTIEPAGKAPAKIISFGGTVTTPWMKDVRLPCNSVGDPAPAVKWTKDSEDSAIPVSMDGHRLIHTNGTLLLRAVKAEDSGYYTCTATNTGGFDTIIVNLLVQVPPDQPRLTVSKTSASSITLTWIPGDNGGSSIRGFVLQYSVDNSEEWKDVFISSSERSFKLDSLKCGTWYKVKLAAKNSVGSGRISEIIEAKTHGREPSFSKDQHLFTHINSTHARLNLQGWNNGGCPITAIVLEYRPKGTWAWQGLRANSSGEVFLTELREATWYELRMRACNSAGCGNETAQFATLDYDGSTIPPIKSAQGEGDDVKKLFTIGCPVILATLGVALLFIVRKKRKEKRLKRLRDAKSLAEMLISKNNRSFDTPVKGPPQGPRLHIDIPRVQLLIEDKEGIKQLGDDKATIPVTDAEFSQAVNPQSFCTGVSLHHPTLIQSTGPLIDMSDIRPGTNPVSRKNVKSAHSTRNRYSSQWTLTKCQASTPARTLTSDWRTVGSQHGVTVTESDSYSASLSQDTDKGRNSMVSTESASSTYEELARAYEHAKLEEQLQHAKFEITECFISDSSSDQMTTGTNENADSMTSMSTPSEPGICRFTASPPKPQDADRGKNVAVPIPHRANKSDYCNLPLYAKSEAFFRKADGREPCPVVPPREASIRNLARTYHTQARHLTLDPASKSLGLPHPGAPAAASTDSLLEMSTSGVGRSQKQGAGAYSKSYTLVSEQ ID NO:2656049 bpNOV92b,CCACAGAGGGGAAATGCCAGCTTCCCTCTCCCTGGGGCTCCGTGCCCCCTCTGATCCACG59754-01 DNA SequenceGCCCTTCGAATTCCCACCCGCCTCCATCGGCCAGCTGCTCTACATTCCCTGTGTGGTGTCCTCGGGGGACATGCCCATCCGTATCACCTGGAGGAAGGACGGACAGGTGATCATCTCAGGCTCGGGCGTGACCATCGAGAGCAAGGAATTCATGAGCTCCCTGCAGATCTCTAGCGTCTCCCTCAAGCACAACGGCAACTATACATGCATCGCCAGCAACGCAGCCGCCACCGTGAGCATTGTGTCTCCAGAACACAGGTTTTTTATTACCTACCACGGCGGGCTGTACATCTCTGACGTACAGAAGGAGGACGCCCTCTCCACCTATCGCTGCATCACCAAGCACAAGTATAGCGGGGAGACCCGGCAGAGCAATGGGGCACGCCTCTCTGTGACAGACCCTGCTGAGTCGATCCCCACCATCCTGGATGGCTTCCACTCCCAGGAAGTGTGGGCCGGCCACACCGTGGAGCTGCCCTGCACCGCCTCGGGCTACCCTATCCCCGCCATCCGCTGGCTCAAGGATGGCCGGCCCCTCCCGGCTGACAGCCGCTGGACCAAGCGCATCACAGGGCTGACCATCAGCGACTTGCGGACCGAGGACAGCGGCACCTACATTTGTGAGGTCACCAACACCTTCGGTTCGGCAGAGGCCACAGGCATCCTCATGGTCATTGATCCCCTTCATGTGACCCTGACACCAAAGAAGCTGAAGACCGGCATTGGCAGCACGGTCATCCTCTCCTGTGCCCTGACGGGCTCCCCAGAGTTCACCATCCGCTGGTATCGCAACACGGAGCTGGTGCTGCCTGACGAGGCCATCTCCATCCGCGGGCTCAGCAACGAGACGCTGCTCATCACCTCGGCCCAGAAGAGCCATTCCGGGGCCTACCAGTGCTTCGCTACCCGCAAGGCCCAGACCGCCCAGGACTTTGCCATCATTGCACTTGAGGATGGCACGCCCCGCATCGTCTCGTCCTTCAGCGAGAAGGTGGTCAACCCCGGGGAGCAGTTCTCACTGATGTGTGCGGCCAAGGGCGCCCCGCCCCCCACAGTCACCTGGGCCCTCGACGATGAGCCCATCGTGCGGGATGGCAGCCACCGCACCAACCAGTACACCATGTCGGACGGCACCACCATCAGCCACATGAACGTCACAGGCCCCCAGATCCGCGACGGGGGCGTGTACCGGTGCACAGCGCGGAACTTGGTGGGCAGTGCTGAATATCAGGCGCGAATAAACGTAAGAGGCCCACCCAGCATCCGGGCTATGCGGAACATCACAGCAGTCGCCGGGCGGGACACCCTTATCAACTGCAGGGTCATCGGCTATCCCTACTACTCCATCAAGTGGTACAAGGATGCCTTGCTGCTGCCAGACAACCACCGCCAGGTGGTGTTTGAGAATGGGACCCTCAAGCTGACTGACGTGCAGAAGGGCAGGGATGAGGGGGAGTACCTGTGCAGTGTCCTCATCCAGCCCCAGCTCTCCATCAGCCAGAGCGTTCACGTAGCCGTCAAAGTGCCCCCTCTGATCCAGCCCTTCGAATTCCCACCCGCCTCCATCGGCCAGCTGCTCTACATTCCCTGTGTGGTGTCCTCGGGGGACATGCCCATCCGTATCACCTGGAGGAAGGACGGACAGGTGATCATCTCAGGCTCGGGCGTGACCATCGAGAGCAAGGAATTCATGAGCTCCCTGCAGATCTCTAGCGTCTCCCTCAAGCACAACGGCAACTATACATGCATCGCCAGCAACGCAGCCGCCACCGTGAGCCGGGAGCGTCAGCTCATCGTGCGTGTGCCCCCTCGATTTGTGGTGCAACCCAACAACCAGGATGGCATCTACGGCAAAGCTGGTGTGCTCAACTGCTCGGTGGACGGCTACCCCCCACCCAAGGTCATGTGGAAGCATGCCAAGGGTAGCGGGAACCCCCAGCAGTACCACCCTGTGCCCCTCACTGGCCGCATCCAGATCCTGCCCAACAGCTCGCTGCTGATCCGCCACGTCCTAGAAGAGGACATCGGCTACTACCTCTGCCAGGCCAGCAACGGCGTAGGCACCGACATCAGCAAGTCCATGTTCCTCACAGTCAAGATCCCCACCATCCTGGATGGCTTCCACTCCCAGGAAGTGTGGGCCGGCCACACCGTGGAGCTGCCCTGCACCGCCTCGGGCTACCCTATCCCCGCCATCCGCTGGCTCAAGGATGGCCGGCCCCTCCCGGCTGACAGCCGCTGGACCAAGCGCATCACAGGGCTGACCATCAGCGACTTGCGGACCGAGGACAGCGGCACCTACATTTGTGAGGTCACCAACACCTTCGGTGAGGCCACAGGCATCCTCATGGTCATTGGTGAGGAGCCCCCCGACCCCCCAGAGCTGGAGATCCGGGAGGTGAAGGCCCGGAGCATGAACCTGCGCTGGACCCAGCGATTCGACGGGAACAGCATCATCACGGGCTTCGACATTGAATACAAGAACAAATCAGATTCCTGGGACTTCAAGCAGTCCACACGCAACATCTCCCCCACCATCAACCAGGCCAACATTGTGGACTTGCACCCGGCATCTGTGTACAGCATCCGCATGTACTCTTTCAACAAGATTGGCCGCAGTGAACCAAGCAAGGAGCTCACCATCAGCACTGAGGAGGCCTCAGCTCCCGATGGGCCCCCCATGGATGTTACCTTGCAGCCAGTGACCTCACAGAGCATCCAGGTGACCTGGAAGCAGGCACCCAAGAAGGAGCTGCAGAACGGTGTCATCCGGGGCTACCAGATTGGCTACAGAGAGAACAGCCCCGGCAGCAACGGGCAGTACAGCATCGTGGAGATGAAGGCCACGGGGGACAGCGAGGTCTACACCCTGGACAACCTCAAGAAGTTCGCCCAGTATGGGGTGGTGGTCCAGGCCTTCAATCGGGCTGGCACGGGGCCCTCTTCCAGCGAGATCAATGCCACCACTCTGGAGGATGTGCCCAGCCAGCCCCCTGAGAACGTCCGGGCCCTGTCCATCACTTCTGACGTGGCCGTCATCTCCTGGTCAGAGCCCCCGCGCAGCACCCTCAATGGCGTCCTCAAAGGCTATCGGGTCATCTTCTGGTCCCTCTATGTTGATGGGGAGTGGGGCGAGATGCAGAACATCACCACCACGCGGGAGCGGGTGGAGCTGCGGGGCATGGAGAAGTTCACCAACTACAGCGTCCAGGTGCTGGCCTACACCCAGGCTGGGGACGGCGTACGCAGCAGTGTGCTCTACATCCAGACCAAGGAGGACGTTCCAGGTCCCCCTGCTGGCATCAAAGCTGTCCCTTCATCAGCTAGCAGTGTGGTTGTGTCTTGGCTCCCCCCTACCAAGCCCAACGGGGTGATCCGCAAGTACACCATCTTCTGTTCCAGCCCCGCCCCGCAGGCTCCCAGCGAGTACGAGACGAGTCCAGAGCAGCTCTTCTACCGGATCGCCCACCTAAACCGCGGTCAGCAGTATCTGCTGTGGGTGGCCGCCGTCACCTCTGCCGGCCGGGGCAACAGCAGCGAGAAGGTGACCATCGAGCCTGCTGGCAAGGCCCCAGCAAAGATCATCTCCTTTGGGGGCACCGTGACAACACCTTGGATGAAAGATGTTCGGCTGCCTTGCAATTCAGTGGGAGATCCAGCCCCTGCTGTGAAGTGGACCAAGGACAGTGAAGACTCGGCCATTCCAGTGTCCATGGATGGGCACCGGCTCATCCACACCAATGGCACACTGCTGCTGCGTGCAGTGAAGGCTGAGGACTCTGGCTACTACACGTGCACGGCCACCAACACTGGTGGCTTTGACACCATCATCGTCAACCTTCTGGTGCAAGTTCCCCCGGACCAGCCCCGCCTCACTGTCTCCAAAACCTCAGCTTCGTCCATCACCCTGACCTGGATTCCAGGTGACAATGGGGGCAGCTCCATCCGAGGTTTTGTGCTACAGTACTCGGTGGACAACAGCGAGGAGTGGAAGGATGTGTTCATCAGCTCCAGCGAGCGCTCCTTCAAGCTGGACAGCCTCAAGTGTGGCACGTGGTACAAGGTGAAGCTGGCAGCCAAGAACAGCGTGGGCTCTGGGCGCATCAGCGAGATCATCGAGGCCAAGACCCACGGGCGGGAGCCCTCCTTCAGCAAAGACCAACACCTCTTCACCCACATCAACTCCACGCATGCTCGGCTTAACCTGCAGGGCTGGAACAATGGGGGCTGCCCTATCACAGCCATCGTTCTGGAGTACCGGCCCAAGGGGACCTGGGCCTGGCAGGGCCTCCGGGCCAACAGCTCCGGGGAGGTGTTTCTGACGGAACTGCGAGAGGCCACGTGGTACGAGCTGCGCATGAGGGCTTGCAACAGTGCGGGCTGCGGCAATGAAACAGCCCAGTTCGCCACCCTGGACTACGATGGCAGTACCATTCCACCCATCAAGTCTGCTCAAGGTGAAGGGGATGATGTGAAGAAGCTGTTCACCATCGGCTGCCCTGTCATCCTGGCCACACTGGGGGTGGCACTGCTCTTCATCGTACGCAAGAAGAGGAAGGAGAAACGGCTGAAGCGACTCCGAGATGCAAAGAGTTTGGCAGAAATGTTGATAAGCAAGAACAATAGAAGCTTTGACACCCCTGTGAAAGGGCCACCCCAGGGCCCACGGCTACACATTGACATCCCCAGGGTCCAGCTGCTCATCGAGGACAAAGAAGGCATCAAGCAACTGGGTGAGGACAAGGCCACCATCCCTGTGACAGATGCTGAGTTCAGCCAAGCTGTCAACCCACAGAGCTTCTGTACTGGCGTCTCCTTGCACCACCCAACCCTCATCCAGAGCACAGGACCCCTCATCGACATGTCTGACATCCGGCCAGGAACCGATCCAGTGTCCAGGAAGAATGTGAAGTCAGCCCACAGCACCCGGAACCGGTACTCAAGCCAGTGGACCCTGACCAAGTGCCAGGCCTCCACACCTGCCCGCACCCTCACCTCCGACTGGCGCACCGTGGGCTCCCAGCATGGTGTCACGGTCACTGAGAGTGACAGCTACAGTGCCAGCCTGTCCCAGGACACAGACAAAGGAAGGAACAGCATGGTGTCCACTGAGAGTGCCTCTTCCACCTACGAGGAGCTGGCCCGGGCCTATGAGCATGCCAAGCTGGAGGAGCAGCTGCAGCACGCCAAGTTTGAGATCACCGAGTGCTTCATCTCTGACAGTTCCTCTGACCAGATGACCACAGGCACCAACGAGAACGCCGACAGCATGACATCCATGAGCACACCCTCAGAGCCTGGCATCTGCCGCTTTACCGCCTCACCACCCAAGCCCCAGGATGCGGACCGGCTGCTGATGCTGGTCCCAGGTGCCCACCTCCCTCCTCAGTCCATCCATGTTGTAGCATATGTCAGAATTTCCTTCTTACTGAACAAGGGTGGGGGAGACCTGGCTTCTGATCTTAGCTCCGGCAGAGCTTGCAGTGAGCCGAGATCACGCGGCACCCGGCCACCAACACTGGTGGCTTTGACACCATCATCGTCAACCTGTGAGGCAGGTGACCCCAGGTGGGGACAGGGATGGAGAAAGGGTAGGGATTCCATCATGCGAGAGGGTCATCGAATGGAAGAAGCCAAACCAAGGGAGAGACAGACCTCTGGAGAAACAGAGGTGCACATGGAAGGGGAGGCAGGAGAGCTGGGGAGTGGGAGTGGGAGTGAGGGTGTGGGAGAGCCAGCACCTTCCCGTCACGGGGGGACTCCCCACACCCCATCACAGGGTCCGCCCTTGTGCTAAGGGGTGGTGGCTTTCCCCTCACAGTTCCCCCGGACCAGCCCCGCCTCACTGTCTCCAAAACCTCAGCTTCGTCCATCACCCTGACCTGGATTCCAGGTGACAATGGGGGCAGCTCCATCCGAGGTGAGGAGGGGTCTGGATGCGGGGGAAGATAGGGGAAGGAATTCTGGGCCCGGGGCAGGGAAGGGGCTTCAORF Start: ATG at 129ORF Stop: TAA at 5853SEQ ID NO:2661908 aaMW at 208575.3 kDNOV92b,MPIRITWRKDGQVIISGSGVTIESKEFMSSLQISSVSLKHNGNYTCIASNAAATVSIVCG59754-01 ProteinSequenceSPEHRFFITYHGGLYISDVQKEDALSTYRCITKHKYSGETRQSNGARLSVTDPAESIPTILDGFHSQEVWAGHTVELPCTASGYPIPAIRWLKDGRPLPADSRWTKRITGLTISDLRTEDSGTYICEVTNTFGSAEATGILMVIDPLHVTLTPKKLKTGIGSTVILSCALTGSPEFTIRWYRNTELVLPDEAISIRGLSNETLLITSAQKSHSGAYQCFATRKAQTAQDFAIIALEDGTPRIVSSFSEKVVNPGEQFSLMCAAKGAPPPTVTWALDDEPIVRDGSHRTNQYTMSDGTTISHMNVTGPQIRDGGVYRCTARNLVGSAEYQARINVRGPPSIRAMRNITAVAGRDTLINCRVIGYPYYSIKWYKDALLLPDNHRQVVFENGTLKLTDVQKGMDEGEYLCSVLIQPQLSISQSVHVAVKVPPLIQPFEFPPASIGQLLYIPCVVSSGDMPIRITWRKDGQVIISGSGVTIESKEFMSSLQISSVSLKHNGNYTCIASNAAATVSRERQLIVRVPPRFVVQPNNQDGIYGKAGVLNCSVDGYPPPKVMWKHAKGSGNPQQYHPVPLTGRIQILPNSSLLIRHVLEEDIGYYLCQASNGVGTDISKSMFLTVKIPTILDGFHSQEVWAGHTVELPCTASGYPIPAIRWLKDGRPLPADSRWTKRITGLTISDLRTEDSGTYICEVTNTFGEATGILMVIGEEPPDPPELEIREVKARSMNLRWTQRFDGNSIITGFDIEYKNKSDSWDFKQSTRNISPTINQANIVDLHPASVYSIRMYSFNKIGRSEPSKELTISTEEASAPDGPPMDVTLQPVTSQSIQVTWKQAPKKELQNGVIRGYQIGYRENSPGSNGQYSIVEMKATGDSEVYTLDNLKKFAQYGVVVQAFNRAGTGPSSSEINATTLEDVPSQPPENVRALSITSDVAVISWSEPPRSTLNGVLKGYRVIFWSLYVDGEWGEMQNITTTRERVELRGMEKFTNYSVQVLAYTQAGDGVRSSVLYIQTKEDVPGPPAGIKAVPSSASSVVVSWLPPTKPNGVIRKYTIFCSSPAPQAPSEYETSPEQLFYRIAHLNRGQQYLLWVAAVTSAGRGNSSEKVTIEPAGKAPAKIISFGGTFTTPWMKDVRLPCNSVGDPAPAVKWTKDSEDSAIPVSMDGHRLIHTNGTLLLRAVKAEDSGYYTCTATNTGGFDTIIVNLLVQVPPDQPRLTVSKTSASSITLTWIPGDNGGSSIRGFVLQYSVDNSEEWKDVFISSSERSFKLDSLKCGTWYKVKLAAKNSVGSGRISEIIEAKTHGREPSFSKDQHLFTHINSTHARLNLQGWNNGGCPITAIVLEYRPKGTWAWQGLRANSSGEVFLTELREATWYELRMRACNSAGCGNETAQFATLDYDGSTIPPIKSAQGEGDDVKKLFTIGCPVILATLGVALLFIVRKKRKEKRLKRLRDAKSLAEMLISKNNRSFDTPVKGPPQGPRLHIDIPRVQLLIEDKEGIKQLGEDKATIPVTDAEFSQAVNPQSFCTGVSLHHPTLIQSTGPLIDMSDIRPGTDPVSRKNVKSAHSTRNRYSSQWTLTKCQASTPARTLTSDWRTVGSQHGVTVTESDSYSASLSQDTDKGRNSMVSTESASSTYEELARAYEHAKLEEQLQHAKFEITECFISDSSSDQMTTGTNENADSMTSMSTPSEPGICRFTASPPKPQDADRLLMLVPGAHLPPQSIHVVAYVRISFLLNKGGGDLASDLSSGRACSEPRSRGTRPPTLVALTPSSSTCEAGDPRWGQGWRKGRDSIMREGHRMEEAKPRERQTSGETEVHMEGEAGELGSGSGSEGVGEPAPSRHGGTPHTPSQGPPLC


[0807] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 92B.
483TABLE 92BComparison of NOV92a against NOV92b.Identities/ProteinNOV92a Residues/Similarities forSequenceMatch Residuesthe Matched RegionNOV92b1 . . . 17711663/1773 (93%)1 . . . 17601681/1773 (94%)


[0808] Further analysis of the NOV92a protein yielded the following properties shown in Table 92C.
484TABLE 92CProtein Sequence Properties NOV92aPSort0.7000 probability located in plasma membrane; 0.3000analysis:probability located in microbody (peroxisome); 0.3000probability located in nucleus; 0.2000 probability locatedin endoplasmic reticulum (membrane)SignalPNo Known Signal Sequence Predictedanalysis:


[0809] A search of the NOV92a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 92D.
485TABLE 92DGeneseq Results for NOV92aNOV92aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAU28091Novel human secretory protein,200 . . . 19431744/1744 (100%)0.0Seq ID No 260-Homo sapiens, 1 . . . 17441744/1744 (100%)1744 aa. [WO200166689-A2,13 SEP. 2001]AAM78713Human protein SEQ ID NO 1375-200 . . . 19431744/1744 (100%)0.0Homo sapiens, 1744 aa. 1 . . . 17441744/1744 (100%)[WO200157190-A2,9 AUG. 2001]AAM39040Human polypeptide SEQ ID NO200 . . . 19431744/1744 (100%)0.02185-Homo sapiens, 1744 aa. 1 . . . 17441744/1744 (100%)[WO200153312-A1,26 JUL. 2001]AAW42086Human Down syndrome-cell 44 . . . 17781085/1745 (62%)0.0adhesion molecule DS-CAM1-154 . . . 18901357/1745 (77%)[WO9817795-A1, 30 APR. 1998]AAW42087Human Down syndrome-cell 44 . . . 1457 890/1416 (62%)0.0adhesion molecule DS-CAM2-154 . . . 15641109/1416 (77%)Homo sapiens, 1571 aa.[WO9817795-A1, 30 APR. 1998]


[0810] In a BLAST search of public sequence databases, the NOV92a protein was found to have homology to the proteins shown in the BLASTP data in Table 92E.
486TABLE 92EPublic BLASTP Results for NOV92aNOV92aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueAAL57166DOWN SYNDROME CELL 44 . . . 19431889/1900 (99%)0.0ADHESION MOLECULE155 . . . 20531892/1900 (99%)DSCAML1-Homo sapiens(Human), 2053 aa.Q9ULT7KIAA1132 PROTEIN-Homo122 . . . 19431822/1822 (100%)0.0sapiens (Human), 1822 aa 1 . . . 18221822/1822 (100%)(fragment).O60469Down syndrome cell adhesion 44 . . . 19431123/1920 (58%)0.0molecule precursor (CHD2)-154 . . . 20121410/1920 (72%)Homo sapiens (Human),2012 aa.Q9ERC8DOWN SYNDROME CELL 44 . . . 19431119/1921 (58%)0.0ADHESION MOLECULE-154 . . . 20131405/1921 (72%)Mus musculus (Mouse),2013 aa.AAL57167DOWN SYNDROME CELL 44 . . . 19431119/1921 (58%)0.0ADHESION MOLECULE154 . . . 20131405/1921 (72%)DSCAM-Rattus norvegicus(Rat), 2013 aa.


[0811] PFam analysis predicts that the NOV92a protein contains the domains shown in the Table 92F.
487TABLE 92FDomain Analysis of NOV92aIdentities/PfamNOV92aSimilarities forExpectDomainMatch Regionthe Matched RegionValueig: domain 1 of 10  1 . . . 4812/49 (24%)2.7e−0538/49 (78%)ig: domain 2 of 10 72 . . . 90 8/19 (42%)8514/19 (74%)ig: domain 3 of 10 130 . . . 18622/60 (37%)2.1e−1446/60 (77%)ig: domain 4 of 10 219 . . . 27816/63 (25%)4.9e−0944/63 (70%)ig: domain 5 of 10 312 . . . 37714/69 (20%)1.5e−0750/69 (72%)ig: domain 6 of 10 409 . . . 46712/61 (20%)4.8e−0541/61 (67%)ig: domain 7 of 10 500 . . . 56117/64 (27%)3.2e−1149/64 (77%)ig: domain 8 of 10 594 . . . 65919/69 (28%)9.4e−0747/69 (68%)ig: domain 9 of 10 693 . . . 759 9/70 (13%)7.9e−0647/70 (67%)fn3: domain 1 of 6 777 . . . 86422/89 (25%) 3e−1665/89 (73%)fn3: domain 2 of 6 876 . . . 96833/93 (35%)3.1e−1668/93 (73%)fn3: domain 3 of 6 980 . . . 106926/93 (28%)2.9e−1669/93 (74%)fn3: domain 4 of 61081 . . . 116724/88 (27%)3.7e−1764/88 (73%)ig: domain 10 of 101194 . . . 125517/65 (26%)4.3e−0946/65 (71%)fn3: domain 5 of 61274 . . . 135730/86 (35%)1.2e−1867/86 (78%)fn3: domain 6 of 61371 . . . 145327/86 (31%) 0.04553/86 (62%)



Example 93

[0812] The NOV93 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 93A.
488TABLE 93ANOV93 Sequence AnalysisSEQ ID NO:2671272 bpNOV93a,AGAGCCTGGTATGCAGGAGGTGCTCTGTAAATACCTGCCCCATACATACCCGCCCCATCG59800-01 DNA SequenceACATACCCACCCCATACATACCCACCCCATACATACCTGCCCTGTCCATACCTCCCCCCTACATACCTGCCCCGTCCATACCTGCCCCCTACATACCTGCCCCGTCCATACCTGCCCCCTACATACCTGCTCTGTCTATACCTGTGGCTAGGACTGTGGCCTTCCTTCTTAGCCGCTCAGAGCCTGCCTCCTCCTCTGCAGAGTGGCGGTGGTAGCAGGGCTTCCCGCGCGCCGATGCTGCTCGTGGCCCTGGTGCTCGGCGCCTACTGCCTCTGCGCCCTCCCCGGCCGCTGCCCGCCCGCCGCCCCCGCCCCCGCGCCCGCCCCCGCGCCCTCCGAGCCGTCCAGCTCCGTCCACCGCCCGGGACCACCCGGCCTGCCTTTGGCCACCGGTCCCGGCCGCCGGCCCTTCCCGCAACCGCTCATCGTTGGCGTGAAGAAGGGCGGCACGCGCGCCCTGCTGGAGTTTCTCCGGCTGCACCCCGACCTCCGCGCGCTCGCCTCTGAGCCCCACTTCTTCGACAGGTGCCCCGACCGCGGCCTCCCCTGGTCCCGCAGTCTGATGCCCCGAACCCTCCATGGGCAGATCACCATGGAGACGACCCCGGGCTACTTCGTGACGCGAGAGGCCCCCCGCCGCATCCACGCCATGTCCCCGGACACGAAGCTGATCGTGGTGGTGCGGAACCCCGTCACCCGGGCCATCTCCGACTAGGCCCACACGCTCTCCAAGACCCCGGGCCTGCCCAGCTTCCGCGCCCTGGCCTTCCGCCACGGCCTGGGCCCCGTGGACACAGCCTGGAGCGCCGTCCGCATCCGCCTGTACGCCCACCACCTGGACCACTGGCTGCGCTACTTCCCCCTGTCCCACTTCCTGTTCGTCAGCGGGGAGCGTCTGGTCAGCGACCCGGCCGGAGAGCTCGGCCGCGTGCAGGACTTCCTGGGCCTGAAACGGGTCGTCACGGACAAGCACTTCTACTTCAACGCCACCAAGGGCTTCCCCTGCCTCAAGAAGGCCCAGGGCGGCAGCCCTCCCCCCTGCCTGGGCAAGTCCAAGGGCCGGCCACACCCACCCGTGCCCCAGGCCGTGGTCCGGCGCCTGCAGGAGTTCTACCCGCCCTTCAACCGCAGGTTCTACCAGATCACGGGCCAGGACTTCGGCTGGGGCTGAGCGGCACCCTGGGCATGCTCAGCACCTTGATTGACACCCGCTCGORF Start: GAG at 2ORF Stop: GGC at 1217SEQ ID NO:268405 aaMW at 43994.8 kDNOV93aMQEVLCKYLPHTYPPHTYPPHTYPPHTYLPCPYLPPTYLPRPYLPPTYLPRPYLPPTYCG59800-01 Protein SequenceLLCLYLWLGLWFCFIQSLFPPLQSGGGSRASRAPMLLVALVLGAYCLCALPGRCPFAARAPAPAPAPSEPSSSVERPGAPGLPLASGPGRRRFPQALIVGVKKGGTRALLEFLRLHPDXRALGSEXEFFDRCXXXCLXWXRSLMPRTLDGQTTMEXTPXYFVTREAPRRIHAMSPDTKLIVVVRNPVTRAISDXXQTLSKTPGLPSFRALAFRHGLGPVDTAWSAVRIGLYAQHLDEWLRYFPLSEELFVSGERLVSDPAGEVGRVQDFLGLKRVVTDKHFYFNATKGFPCLKKAQGGSRPRCLGKSKGRPHPRVPQAXVRRLQEFYRPFNRRFYQMTGQDFGWG


[0813] Further analysis of the NOV93a protein yielded the following properties shown in Table 93B.
489TABLE 93BProtein Sequence Properties NOV93aPSort0.6000 probability located in plasma membrane; 0.4000analysis:probability located in Golgi body; 0.3000 probabilitylocated in endoplasmic reticulum (membrane); 0.1000probability located in mitochondrial inner membraneSignalPLikely cleavage site between residues 7 and 8analysis:


[0814] A search of the NOV93a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 93C.
490TABLE 93CGeneseq Results for NOV93aNOV93aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAB95507Human protein sequence SEQ ID31 . . . 253121/229 (52%)4e−55NO: 18067-Homo sapiens, 390 aa.11 . . . 237146/229 (62%)[EP1074617-A2, 7 FEB. 2001]AAY17066Human 3-OST-3B protein-Homo31 . . . 253121/229 (52%)4e−55sapiens, 390 aa. [WO9922005-A2,11 . . . 237146/229 (62%)6 MAY 1999]AAB70115Human 3-OST-3B-Homo sapiens,31 . . . 253121/230 (52%)9e−54391 aa. [WO200113910-A2,11 . . . 238146/230 (62%)1 MAR. 2001]AAB70114Murine 3-OST-3B-Mus sp, 39131 . . . 253119/231 (51%)2e−51aa. [WO200113910-A2,11 . . . 238147/231 (63%)1 MAR. 2001]AAU12275Human PRO5004 polypeptide86 . . . 253102/170 (60%)9e−48sequence-Homo sapiens, 367 aa.45 . . . 214117/170 (68%)[WO200140466-A2, 7 JUN. 2001]


[0815] In a BLAST search of public sequence databases, the NOV93a protein was found to have homology to the proteins shown in the BLASTP data in Table 93D.
491TABLE 93DPublic BLASTP Results for NOV93aNOV93aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueQ96QI5C439A6.1 (NOVEL PROTEIN85 . . . 253160/169 (94%)2e−89SIMILAR TO HEPARAN61 . . . 229162/169 (95%)SULFATE (GLUCOSAMINE) 3-O-SULFOTRANSFERASES)-Homosapiens (Human), 381 aa (fragment).Q96RX7HEPARAN SULPHATE D-95 . . . 253153/159 (96%)1e−85GLUCOSAMINYL 3-O- 1 . . . 159155/159 (97%)SULFOTRANSFERASE-3B LIKE-Homo sapiens (Human), 311 aa.Q9Y662HEPARAN SULFATE D-31 . . . 253121/229 (52%)1e−54GLUCOSAMINYL 3-O-11 . . . 237146/229 (62%)2.8.2.23)-Homo sapiens (Human),390 aa.Q9QZS6D-GLYCOSAMINYL 3-O-31 . . . 253119/230 (51%)3e−52SULFOTRANSFERASE-3B-Mus11 . . . 237147/230 (63%)musculus (Mouse), 390 aa.Q9Y278HEPARAN SULFATE D-86 . . . 253102/170 (60%)3e−47GLUCOSAMINYL 3-O-45 . . . 214117/170 (68%)SULFOTRANSFERASE-2 (EC2.8.2.23)-Homo sapiens (Human),367 aa.


[0816] PFam analysis predicts that the NOV93a protein contains the domains shown in the Table 93E.
492TABLE 93EDomain Analysis of NOV93aIdentities/PfamNOV93aSimilarities forExpectDomainMatch Regionthe Matched RegionValueNo Significant Matches Found


[0817] The NOV94 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 94A.
493TABLE 94ANOV94 Sequence AnalysisSEQ ID NO:2692949 bpNOV94a,GTCCGCCTCCCGGCCGCCGAGCCGCAGCCGCCGAGATGCGCGCCGCCCCGGGCCGCGCCG59761-01 DNA SequenceCCCCGCCGGGTCCCGCCCGCCCCGCTGCCGCTGAGCGCATGGGCCCGGACCGCGCCGCGCCGCTCCGGGAGCCGGGCCCGCGGTCCCGCCACCACCCCGCGCGGGACAGATTCATTCACTTTGGAGCTGTAAGTACTGATGTATTAGGGTGCAGCCCTCATTGTTCATTGACGCACAGTCCCAAAATGAATATCCAAGAGCAGGGTTTCCCCTTCGACCTCGGAGCAAGTTTCACCGAAGATGCTCCCCGACCCCCAGTCCCTCGTGAGGAGCGAGAACTCGTGTCCACAGACCCGAGGCCCGCCAGCTACAGTTTCTGCTCCGGGAAAGGTGTTGGCATTAAAGGTGAGACTTCGACGGCCACTCCGAGGCGCTCGGATCTCGACCTGGGGTATGAGCCTGAGGGCAGTCCCTCCCCCACCCCACCATACTTGAAGTGGGCTGAGTCACTGCATTCCCTGCTGGATGACCAAGATGGGATAAGCCTGTTCAGGACTTTCCTGAAGCAGGAGGGCTGTGCCGACTTGCTGCACTTCTGGTTTGCCTGCACTGCCTTCAGCAACCTGGAGCCCTGTCACTCGAACGAGGAGAAGAGGCTGAAGCTGGCGAGAGCCATCTACCCAAAGTACATTCTTGATAACAATGGCATCGTGTCCCGGCAGACCAAGCCAGCCACCAAGAGCTTCATAAAGGGCTGCATCATGAAGCAGCTGATCGATCCTCCCATGTTTGACCAGGCCCAGACCGAAATCCAGGCCACTATGGAGGAAAACACCTATCCCTCCTTCCTTAAGTCTCATATTTATTTGGAATATACGAGGACAGGCTCGGAGAGCCCCAAAGTCTGTAGTGACCAGACCTCTGCGTCAGGGACAGGGAAGGGCATATCTGGATACCTGCCGACCTTAAATGAAGATGAGGAATGGAAGTGTGACCAGGACATGGATCACGACGATGGCAGAGACGCTGCTCCCCCCGGAAGACTCCCTCAGAAGCTGCTCCTGGAGACAGCTGCCCCGAGGGTCTCCTCCAGTAGACGGTACAGCGAAGGCAGAGAGTTCAGGTATGGATCCTGGCGGGAGCCAGTCAACCCCTATTATGTCAATGCCGGCTATGCCCTGGCCCCAGCCACCAGTGCCAACCACAGCGAGCAGCAGAGCCTGTCCAGCGATGCAGACACCCTGTCCCTCACGGACAGCAGCGTGGATGGGATCCCCCCATACAGGATCCGTAAGCAGCACCGCAGGGAGATGCAGGAGAGCGTGCAGGTCAATGGGCGGGTGCCCCTACCTCACATTCCCCGCACGTACCGGGTGCCGAAGGAGGTCCGCGTGGAGCCTCAGAAGTTCGCGGAGGACCTCATCCACCGCCTGGAGGCTGTGCAGCGCACGCCGGAGGCCGAGGAGAAGCTGGAGGAGCGGCTGAAGCGCGTGCGCATGGAGGAGGAAGGTGAGGACGGCGATCCATCATCAGGGCCCCCAGGGCCGTGTCACAAGCTGCCTCCCGCCCCCGCTTGGCACCACTTCCCGCCCCGCCTGTGTTGGACATGGGCTTGTGCCGGGCTCCGGGATGCACACGAGGAGAACCCTGAGAGCATCCTGGACGAGCACGTACAGCGTGTGCTGACGACACCTGGCCGCCAGTCGCCTGGGCCTGGCCATCGCTCCCCGGACAGTGGGCACGTGGCCAAGATGCCAGTGGCACTGGGGGGTGCCGCCTCGGGGCACGGGAAGCACGTACCCAAGTCAGGGGCGAAGCTGGACGCGGCCGGCCTGCACCACCACCGACACGTCCACCACCACGTCCACCACAGCACAGCCCGGCCCAAGGAGCAGGTGGAGGCCGAGGCCACCCGCAGGGCCCAGAGCACCTTCGCCTCGGGCCTGGAACCACACAGCCATGGCGCAAGGTCCCGAGCCTACTCAGAGAGTGTTCGCGCTGCCCCCAACGCCAGTGATGGCCTCGCCCACACTGGGAAGGTGGGCGTGGCGTGCAAAAGAAATGCCAAGAAGGCCGAGTCGGGGAAGAGCGCCAGCACCCAGGTGCCAGGTGCCTCGGAGGATGCGGAGAAGAACCAGAAAATCATGCAGTGGATCATTGAGGGGGAAAAGGAGATCAGCAGCCACCGCACCACCGCCCACGGGTCTTCGGGGACCAGGAAGCCACAGCCCCATGAGAACTCCAGACCCTTGTCCCTTGAGCACCCCTGCCCCGGCCCTCAGCTCCGGACCTCCGTGCAGCCCTCCCACCTCTTCATCCAAGACCCCACCATGCCACCCCACCCAGCTCCCAACCCCCTAACCCAGCTGGAGGAGGCGCGCCGACGTCTCGAGGAGCAAGAAAACAGAGCCAGCCGAGCACCCTCCAAGCAGACGTATCTCCAGCAGGTTATGCCGCGCGGACGCGCCTCCGTCAGGCCAGCGTCCGCGCCGGTCCTGCACGTGGTACCAGCCGTGTCGGACATGGAGCTCTCCGAGACAGAGACAAGATCGCAGAGGAAGGTCCGCGGCGGGAGTGCCCAGCCGTGTGACAGCATCGTTGTGGCCTACTACTTCTGCGGGGAACCCATCCCCTACCGCACCCTGGTGAGGGGCCGCGCTGTCACCCTGGGCCAGTTCAAGGAGCTGCTGACCAAAAAGGGCAGCTACAGATACTACTTCAAGAAAGTGAGCGACGAGTTTGACTGTGCGGTGGTGTTTGAGGAGGTTCGAGAGGACGAGGCCGTCCTGCCCGTCTTTGAGGAGAACATCATCGGCAAAGTGGAGAAGGTGGACTGATAGGCTGGTGGGCTGGCCCCTGTGCCAGGCGACCCCCTTGGCGGGCACGGGTGTCACGGCCAGGCAGATCACCTCGTACTCAGGAGCCCGATGGGGAACAGTGTTGCCTGTACCORF Start: ATG at 97ORF Stop: TGA at 2833SEQ ID NO:270912 aaMW at 101118.1 kDNOV94a,MGPDRAAPLREPGPGSRHHRARDRLIHFGAVSTDVLGCSAHCSLTQSPKMNIQEQGFPCG59761-01 Protein SequenceLDLGASFTEDAPRPPVPGEEGELVSTDPRPASYSFCSGKGVGIKGETSTATPRRSDLDLGYEPEGSASPTPPYLKWAESLHSLLDDQDGISLFRTFLKQEGCADLLDFWFACTGFRKLEPCDSNEEKRLKLARAIYRKYILDNNGIVSRQTKPATKSFIKGCIMKQLIDPAMFDQAQTEIQATMEENTYPSFLKSDIYLEYTRTGSESPKVCSDQSSGSGTGKGISGYLPTLNEDEEWKCDQDMDEDDGRDAAPPGRLPQKLLLETAAPRVSSSRRYSEGREFRYGSWREPVNPYYVNAGYALAPATSANDSEQQSLSSDADTLSLTDSSVDGIPPYRIRKQHRREMQESVQVNGRVPLPHIPRTYRVPKEVRVEPQKFAEELIHRLEAVQRTREAEEKLEERLKRVRMEEEGEDGDPSSGPPGPCHKLPPAPAWHHFPPRLCWTWACAGLRDAHEENPESILDEHVQRVLRTPGRQSPGPGHRSPDSGHVAKMPVALGGAASGHGKHVPKSGAKLDAAGLHHHRHVHHHVHHSTARPKEQVEAEATRRAQSSFAWGLEPHSHGARSRGYSESVGAAPNASDGLAHSGKVGVACKRNAKKAESGKSASTEVPGASEDAEKNQKIMQWIIEGEKEISRHRRTGHGSSGTRKPQPHENSRPLSLEHPWAGPQLRTSVQPSHLFIQDPTMPPHPAPNPLTQLEEARRRLEEEEKRASRAPSKQRYVQEVMRRGRACVRPACAPVLHVVPAVSDMELSETETRSQRKVGGGSAQPCDSIVVAYYFCGEPIPYRTLVRGRAVTLGQFKELLTKKGSYRYYFKKVSDEFDCGVVFEEFREDEAVLPVFEEKIIGKVEKVD


[0818] Further analysis of the NOV94a protein yielded the following properties shown in Table 94B.
494TABLE 94BProtein Sequence Properties NOV94aPSort0.6000 probability located in nucleus; 0.3000 probabilityanalysis:located in microbody (peroxisome); 0.1000 probability locatedin mitochondrial matrix space; 0.1000 probability located inlysosome (lumen)SignalPNo Known Signal Sequence Predictedanalysis:


[0819] A search of the NOV94a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 94C.
495TABLE 94CGeneseq Results for NOV94aNOV94aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAG68175Wnt signaling protein SEQ ID13 . . . 912898/900 (99%)0.0NO: 91-Homo sapiens, 900 aa. 1 . . . 900898/900 (99%)[WO200177327-A1,18 OCT. 2001]AAW96264Human axin-Homo sapiens, 90013 . . . 912898/900 (99%)0.0aa. [WO9902179-A1, 1 . . . 900898/900 (99%)21 JAN. 1999]AAW96265Murine axin-Mus musculus, 992 6 . . . 912781/914 (85%)0.0aa. [WO9902179-A1,84 . . . 992820/914 (89%)21 JAN. 1999]AAW93569Human conductin protein-Homo60 . . . 912378/892 (42%)e−171sapiens, 840 aa. [WO9911780-A2,12 . . . 840506/892 (56%)11 MAR. 1999]AAW93570Human conductin protein-Homo60 . . . 912378/892 (42%)e−171sapiens, 840 aa. [WO9911780-A2,12 . . . 840506/892 (56%)11 MAR. 1999]


[0820] In a BLAST search of public sequence databases, the NOV94a protein was found to have homology to the proteins shown in the BLASTP data in Table 94D.
496TABLE 94DPublic BLASTP Results for NOV94aNOV94aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueO15169Axin 1 (Axis inhibition protein 1)13 . . . 912898/900 (99%)0.0(hAxin)-Homo sapiens (Human), 1 . . . 900898/900 (99%)900 aa (fragment).Q96S28AXIN-Homo sapiens (Human),50 . . . 912858/863 (99%)0.0862 aa. 1 . . . 862858/863 (99%)O35625Axin 1 (Axis inhibition protein 1) 6 . . . 912781/914 (85%)0.0(Fused protein)-Mus musculus84 . . . 992820/914 (89%)(Mouse), 992 aa (fragment).O70239Axin 1 protein (Axis inhibition 6 . . . 912756/914 (82%)0.0protein 1) (rAxin)-Rattus21 . . . 893793/914 (86%)norvegicus (Rat), 893 aa(fragment).T08422negative regualtor axin [imported]-46 . . . 912726/872 (83%)0.0rat, 832 aa. 2 . . . 832760/872 (86%)


[0821] PFam analysis predicts that the NOV94a protein contains the domains shown in the Table 94E.
497TABLE 94EDomain Analysis of NOV94aIdentities/PfamNOV94aSimilarities forExpectDomainMatch Regionthe Matched RegionValueRGS: domain 1 of 2137 . . . 19823/75 (31%)5.6e−0644/75 (59%)RGS: domain 2 of 2231 . . . 26013/30 (43%)0.1221/30 (70%)TP2: domain 1 of 1585 . . . 70933/147 (22%)9.652/147 (35%)DIX: domain 1 of 1830 . . . 91240/86 (47%)5.6e−4483/86 (97%)



Example 95

[0822] The NOV95 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 95A.
498TABLE 95ANOV95 Sequence AnalysisSEQ ID NO:2712223 bpNOV95a,TTGCAGGCATCACCCACGCCCTCTGCACCCACGCTGGAGGACGGGGAGGTTGTCAGGGCG59756-01 DNA SequenceGCTATGATGAGATGAGTCGGGGCCGCTTCGACTTTGATGATGGAGGGGCGTACTGCGGGGGCTGGGAGGGGGGAAAGGCCCATGGGCATGGACTGTGCACAGGCCCCAAGGGCCAGGGCGAATACTCTCGCTCCTGGAACTTTGGCTTTGAGGTGGCAGGTGTCTACACCTCGCCCAGCGGAAACACCTTTGAGGGATACTGGAGCCAGGGCAAACGGCATGGGCTGGGCATAGAGACCAAGGGGCGCTGGCTCTACAAGGCCGAGTGGACACATGGCTTCAAGGGACGCGCCTGCAAGACGGCTATGGCACCGAGACCTATGCTGATGGAGGGACGTACCAAGGCCAGTTCACCAACGGCATGCGCCATGGCTACGGAGTACGCCAGAGCGTGCCCTACGGGATGGCAACCGCACGGTGGCCCCGGACTCTCCCGCCTCGCCGGCCTCCGACGGCCCCGCGCTGCCCTCGCCCGCCATCCCGCGTGGCGGCTTCGCGCTCAGCCTCCTGGCCAATGCCGAGGCGGCCGCGCGGGCGCCCAAGGGCGGCGGCCTCTTCCAGCGGGCCGCGCTGCTGGGCAACCTGCGGCGCGCAGAGTCGCGCACGTCCGTGGGTAGCCAGCGCAGCCGTGTCAGCTTCCTTAAGAGCGACCTCAGCTCGGGCGCCAGCGACGCCGCGTCCACCGCCAGCCTGCGAGAGGCCGCCGAGGGCGCCGACGAGGCCGCACCCTTCGAGGCCGATATCGACGCCACCACCACCGAGACCTACATGGGCGAGTGGAAGAACGACAAACGCTCGGGCTTCGGCGTGACCGAACGCTCCAGTGGCCTCCGCTACGAGGGCGAGTGGCTGGACAACCTGCGCCACGGCTATGGCTCCACCACGCTGCCCGACGGCCACCCCGAGGAGGGCAAGTACCGCCACAACGTGCTGGTCAAGGACACCAAGCGCCGCATGCTGCAGCTCAAGAGCAACAAGGTCCGCCAGAAAGTGGAGCACAGTGTGGAGGGTGCCCAGCGCGCCGCTGCTATCGCGCCCCAGAAGGCCGAGATTGCCGCCTCCAGGACAAGCCACGCCAAGGCCAAAGCTGAGGCAGCGGAACAGGCCGCCCTGGCTGCCAACCAGGACTCCAACATTGCTCGCACTTTGGCCAGGGAGCTGGCTCCGGACTTCTACCAGCCAGGTCCGGAATATCAGAAGCGCCGGCTGCTGCAGGAGATCCTGGAGAACTCGGAGAGCCTGCTGGAGCCCCCCGACCGGGGCGCCGGCGCAGCGGGCCTCCGACAGCCGCCCCGCGAGAGCCCGCAGCTGCACGAGCGTGAGACCCCTCGGCCCGAGGGTCCCTCCCCGTCACCGGCCGGGACGCCCCCGCAGCCCAAGCGGCCCAGGCCCGGGGTGTCCAAGGACCGCCTGCTGAGCCCAGGCGCCTGGAACGGCGAGCCCAGCGGTGAGGGCAGCCGGTCAGTCACTCCGTCCGAGGGCGCGGGCCGCCGCAGCCCCGCGCGTCCAGCCACCGAGCGCATGGCCATCGAGGCTCTGCAGGCACCGCCTGCGCCGTCGCGGGAGCCGGAGGTGGCGCTTTACCAGGGCTACCACACCTATGCTGTGCGCACCACCCCGCCCGAGCCCCCACCCTTTGACGACCAGCCCGACCCCGACGTCTCCGGGTCCGAGTCCGCGCCCTCGTCCCCCGCCACCGCCCCCCTGCAGGCCCCCACCCTCCGAGGCCCCGAGCCTGCACGCGAGACCCCCGCCAAGCTGGAGCCCAAGCCCATCATCCCCAAAGCCGAGCCCAGGGCCAAGGCCCGCAAGACTGAGGCTCCAGGGCTGACCAAGGCGGGGGCCAAGAAGAAGGCGCGGAAGGAGGCCGCACTGGCGGCAGAGGCGGAGGTGGAGGTGGAAGAGGTCCCCAACACCATCCTCATCTGCATGGTGATCCTGCTGAACATCGGCCTGGCCATCCTCTTTGTTCACCTCCTGACCTGACCGTCGCTTACCAGGTGCAGCCAGCTGGCTGCAGGAGGGGTTGGGGGGCAGGAGCCCCTGGGGORF Start: ATG at 70ORF Stop: TGA at 2158SEQ ID NO:272696 aaMW at 74220.7 kDNOV95a,MSGGRFDFDDQCAYCGGWEGGKAEGHQLCTGPKCQGEYSGSFGFEVAGVYTWPSGNCG59756-01 Protein SequenceTFEGYWSQGKRHGLGIETKGRWLYKGEWTHGFKGRYGIRQSSSSGAKYEGTWNNGLQDGYGTETYADGGTYQGQFTNGMRHGYCVRQSVPYGMAVVVRSPLRTSLSSLRSEHSNGTVAPDSPASPASDCPALPSPAIPRGGFALSLLANAEAAAPAPKGGGLFQRGAILGRLRRAESRTSVGSQRSRVSFLKSDLSSGASDAASTASLGEAAEGADEAAPFEADTDATTTETYMGEWKNDKRSGFGVSERSSGLRYEGEWLDNLRHGYGCTTLPDGHREEGKYRHNVLVKDTKRRMLQLKSNKVRQKVEHSVEGAQRAAAIARQKAEIAASRTSHAKAKAEAAEQAALAANQESNIARTLARELAPDFYQPGPEYQKRRLLQEILENSESLLEPPDRGAGAAGLPQPPRESPQLHERETPRPEGGSPSPAGTPPQPKRPRPGVSKDGLLSPGAWNGEPSGEGSRSVTPSEGAGRRSPARPATERMAIEAIQAPPAPSREPEVALYQGYHSYAVRTTPPEPPPFEDQPEPEVSGSESAPSSPATAPLQAFTLRGPEPARETPAKLEPKPIIPKAEPRAKARKTEARCLTKACAKKKARKEAALAAEAEVEVEEVPNTILICMVILLNICLAILFVHLLT


[0823] Further analysis of the NOV95a protein yielded the following properties shown in Table 95B.
499TABLE 95BProtein Sequence Properties NOV95aPSort0.8000 probability located in nucleus; 0.7000 probabilityanalysis:located in plasma membrane; 0.3133 probability located inmicrobody (peroxisome); 0.2000 probability located inendoplasmic reticulum (membrane)SignalPNo Known Signal Sequence Predictedanalysis:


[0824] A search of the NOV95a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 95C.
500TABLE 95CGeneseq Results for NOV95aNOV95aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAM79123Human protein SEQ ID NO 1785- 3 . . . 696293/704 (41%) e−127Homo sapiens, 628 aa. 4 . . . 628377/704 (52%)[WO200157190-A2, 9 AUG. 2001]AAM80107Human protein SEQ ID NO 3753-283 . . . 696146/421 (34%)2e−43Homo sapiens, 378 aa. 24 . . . 378194/421 (45%)[WO200157190-A2, 9 AUG. 2001]ABB21683Protein #3682 encoded by probe for257 . . . 389 78/133 (58%)7e−42measuring heart cell gene expression- 6 . . . 135104/133 (77%)Homo sapiens, 135 aa.[WO200157274-A2, 9 AUG. 2001]AAM57089Human brain expressed single exon257 . . . 389 78/133 (58%)7e−42probe encoded protein SEQ ID NO: 6 . . . 135104/133 (77%)29194-Homo sapiens, 135 aa.[WO200157275-A2, 9 AUG. 2001]AAM17323Peptide #3757 encoded by probe for257 . . . 389 78/133 (58%)7e−42measuring cervical gene expression- 6 . . . 135104/133 (77%)Homo sapiens, 135 aa.[WO200157278-A2, 9 AUG. 2001]


[0825] In a BLAST search of public sequence databases, the NOV95a protein was found to have homology to the proteins shown in the BLASTP data in Table 95D.
501TABLE 95DPublic BLASTP Results for NOV95aNOV95aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueQ9GKY7JUNCTOPHILIN TYPE 2- 1 . . . 696644/701 (91%)0.0Oryctolagus cuniculus (Rabbit), 694 aa. 1 . . . 694662/701 (93%)Q9ET79JUNCTOPHILIN TYPE 2-Mus 1 . . . 696608/706 (86%)0.0musculus (Mouse), 696 aa. 1 . . . 696644/706 (91%)Q9BR39DJ1108D11.1 (NOVEL PROTEIN128 . . . 672544/545 (99%)0.0SIMILAR TO C. ELEGANS T22C1.7)- 1 . . . 545544/545 (99%)Homo sapiens (Human), 552 aa(fragment).Q9GKY8MITSUGUMIN72/JUNCTOPHILIN 1 . . . 696364/704 (51%)0.0TYPE1-Oryctolagus cuniculus 1 . . . 662468/704 (65%)(Rabbit), 662 aa.Q9ET80JUNCTOPHILTN TYPE 1-Mus 1 . . . 696371/707 (52%)0.0musculus (Mouse), 660 aa. 1 . . . 660469/707 (65%)


[0826] PFam analysis predicts that the NOV95a protein contains the domains shown in the Table 95E.
502TABLE 95EDomain Analysis of NOV95aIdentities/PfamNOV95aSimilarities forExpectDomainMatch Regionthe Matched RegionValueMORN: domain 1 of 7 14 . . . 3610/23 (43%)1.113/23 (57%) MORN: domain 2 of 7 38 . . . 59 9/23 (39%)0.3115/23 (65%)MORN: domain 3 of 7 60 . . . 77 8/23 (35%)315/23 (65%)MORN: domain 4 of 7106 . . . 12811/23 (48%)3.7e−0620/23 (87%)MORN: domain 5 of 7129 . . . 151 8/23 (35%)0.02715/23 (65%)MORN: domain 6 of 7291 . . . 31312/23 (52%)0.0005619/23 (83%)MORN: domain 7 of 7314 . . . 33611/23 (48%)0.0002219/23 (83%)



Example 96

[0827] The NOV96 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 96A.
503TABLE 96ANOV96 Sequence AnalysisSEQ ID NO:2733257 bpNOV96a,CGTAGGCGCTTCGGCCATGACTGCGGAGCTGCAGCAGGACGACGCGGCCGGCGCGGCACG59708-01 DNA SequenceGACGGCCACGGCTCGAGCTGCCAAATGCTGTTAAATCAACTGAGAGAAATCACAGGCATTCAGGACCCTTCCTTTCTCCATGAAGCTCTGAAGGCCAGTAATCGTCACATTACTCAGGCAGTCAGCCTTCTCACTGATGAGAGAGTTAAGGAGCCCAGTCAAGACACTGTTGCTACAGAACCATCTGAACTAGAGGCGACTGCTGCCAACAAGGAAGTATTAGCAAAAGTTATAGACCTTACTCATGATAACAAAGATGATCTTCAGGCTGCCATTGCTTTGAGTCTACTGGAGTCTCCCAAAATTCAAGCTGATGGAAGAGATCTTAACAGGATGCATGAAGCAACCTCTGCAGAAACTAAACGCTCAAAGAGAAAACGCTGTGAAGTCTGGGGAGAAAACCCCAATCCCAATGACTGGAGGAGAGTTGATGGTTGGCCAGTTGGGCTGTAAAATGTTGGCAATACATGTTGGTTTAGTGCTGTTATTCAGTCTCTCTTTCAATTGCCTCAATTTCGAAGACTTGTTCTCAGTTATAGTCTGCCACAAAATGTACTTGAAAATTGTCGAAGTCATACAGAAAAGAGAAATATCATGTTTATGCAAGAGCTTCAGTATTTGTTTGCTCTAATGATGGGATCAAATAGAAAATTTGTAGACCCCTCTGCAGCCCTGGATCTATTAAAGGGAGCATTCCGATCATCTGAGGAACAGCAGCAAGATGTGAGTGAATTCACACACAACCTCCTGGATTGGCTAGACCACGCATTCCAGCTACCTGTTAATGTTAACAGTCCCAGGAACAAATCTGAAAATCCAATGGTGCAGCTGTTCTATGGTACTTTCCTGACTGAAGGGCTTCGTGAAGGAAAACCCTTTTGTAACAATGAGACCTTCGGCCAGTATCCTCTTCAGCTAAACGGTTATCGCAACTTACACGAGTGTTTGCAAGGGGCCATGGTGCAGGGTGATGTTCAGCTTCTTCCCTCCGATCACTCGGTGAAGTATGGACAAGAGCGTTGGTTTACAAAGCTACCTCCAGTGTTCACCTTTGAACTCTCAAGATTTGAGTTTAATCACTCCCTTGGGCAGCCAGAGAAAATTCACAATAAGCTGGAATTTCCTCAGATTATTTATATGGACACCTACATGTACACGAGCAAGGAGCTTATTCGAAATAAGAGAGAGTGTATTCGAAAGTTGAAGGAGGAAATAAAAATTCTGCAGCAAAAATTGGAAAGGTATGTGAAATATCGCTCAGGCCCAGCTCGCTTCCCGCTCCCGGACATGCTGAAATATGTTATTGAATTTGCTAGTACAAAACCTGCCTCAGAAAGCTGTCCACCTGAAAGTGACACACATATGACATTACCACTTTCTTCAGTGCACTGCTCGGTTTCTGACCAGACATCCAAGGAAAGTACAAGTACAGAAAGCTCTTCTCAGGATGTTGAAAGTACCTTTTCTTCTCCTGAAGATTCTTTACCCAAGTCTAAACCACTGACATCTTCTCGGTCTTCCATGGAAATGCCTTCACAGCCAGCTCCACGAACAGTCACAGATGAGGAGATAAATTTTGTTAAGACCTCTCTTCAGAGATGGAGGACTGAGATTGAACAAGATATACAAGATTTAAAGACTTGTATTGCAAGTACTACTCAGACTATTGAACAGATGTACTGCGATCCTCTCCTTCGTCAGGTGCCTTATCGCTTGCATGCAGTTCTTGTTCATGAAGGACAAGCAAATCCTGGACACTATTGGGCCTATATCTATAATCAACCCCGACAGAGCTGGCTCAAGTACAATGACATCTCTGTTACTGAATCTTCCTGGGAAGAAGTTGAAAGAGATTCCTATGGAGGCCTGAGAAATGTTAGTCCTTACTGTCTGATGTACATTAATGCCAAACTACCCTACTTCAATCCAGAGGCAGCCCCAACTGAATCAGATCAAATGTCAGAAGTGGAAGCCCTATCTGTGGAACTCAAGCATTACATTCAGGAGGATAACTGGCGGTTTGAGCAGGAAGTAGAGGAGTGGGAAGAAGAGCAGTCTTGCAAAATCCCTCAAATGGAGTCCTCCCCCAACTCCTCATCACAGGGCTACTCTACATCACAAGAGCCTTCAGTAGCCTCTTCTCATGGGGTTCGCTGCTTGTCATCTGAGCATGCTGTGATTGTAAAGGAGCAAACTGCCCAGGCTATTGCAAACACAGCCCGTGCCTATGAGAAGAGCGGTGTAGAAGCGGCACTGAGTGAGGCATTCCATGAAGAATACTCCAGGCTCTATCAGCTTGCCAAAGAGACCCCCACCTCTCACAGTGATCCTCGACTTCAGCATGTCCTTGTCTACTTTTTCCAAAATGAAGCACCCAAAAGGGTAGTAGAACGAACGCTTCTGGAACAGTTTGCAGATAAAAATCTTAGCTATGATGAAAGATCAATCAGCATTATGAAGGTGGCTCAAGCGAAACTGAAGGAAATTGGTCCAGATGAGATGAATATGGAAGAGTACAAGAGGTGGCATGAAGATTATAGTTTGTTCCGAAAAGTGTCTGTGTATCTCCTAACAGCCCTACAACTCTATCAAAAAGGAAAGTACCAAGACGCACTTTCCTACCTGGTATATGCCTACCAGAGCAATGCTGCCCTGCTGATGAAGGGGCGGCATTAATGTGATGAATGAACTGATCATCCCCTGCATTCACCTTATCATTAATAATGACATTTCCAAGGATGATCTGGATGCCATTGAGGTCATGAGAAACCATTGGTGCTCTTACCTTGGGCAAGATATTGCAGAAAATCTGCAGCTGTGCCTAGGCGAGTTTCTACCCAGACTTCTAGATCCTTCTGCAGAAATCATCGTCTTGAAAGAGCCTCCAACTATTCGACCCAATTCTCCCTATGACCTATGTAGCCGATTTGCAGCTGTCATGGAGTCAATTCAGGGAGTTTCAACTGTGACAGTGAAATAAGCTCCCACATGTTCAAGGCCCATTCTGGTTCCTGGCTGCCTGCCTCTTGCACACAAGTTCGTTGTCATAGTCCTCACCTTGGGAAAAGGATTAGGTGGGCACAORF Start: ATG at 17ORF Stop: TAA at 3152SEQ ID NO:2741045 aaMW at 119041.7 kDNOV96a,MTAELQQDDAAGAADGHGSSCQMLLNQLREITGIQDPSFLHEALKASNGDITQAVSLLCG59708-01 ProteinSequenceTDERVKBPSQDTVATEPSEVEGSAANKEVLAKVTDLTHDNKDDLQAAIALSLLESPKIQADGRDLNRMHEATSAETKRSKRKRCEVWGENPNPNDWRRVDGWPVGLKNVGNTCWFSAVIQSLFQLPEFRRLVLSYSLPQNVLENCRSHTEKRNIMFMQELQYLFALMMGSNRKFVDPSAALDLLKGAFRSSEEQQQDVSEFTHKLLDWLEDAFQLAVNVNSPRNKSENPMVQLFYGTFLTEGVREGKPFCNNETFGQYPLQVNGYRNLDECLEGAMVEGDVELLPSDHSVKYGQERWFTKLPPVLTFELSRFEFNQSLGQPEKIHNKLEFPQIIYMDRYMYRSKELIRNKRECIRKLKEEIKILQQKLERYVKYGSGPARFPLPDMLKYVIEFASTKPASESCPPESDTHMTLPLSSVHCSVSDQTSKESTSTESSSQDVESTFSSPEDSLPKSKPLTSSRSSMEMPSQPAPRTVTDEEINFVKTCLQRWRSEIEQDIQDLKTCIASTTQTIEQMYCDPLLRQVPYRLHAVLVHEGQANAGHYWAYIYNQPRQSWLKYNDISVTESSWEEVERDSYGGLRNVSAYCLMYINAKLPYFNAEAAPTESDQMSEVEALSVELKHYIQEDNWRFEQEVEEWEEEQSCKIPQMESSPNSSSQGYSTSQEPSVASSHGVRCLSSEHAVIVKEQTAQAIANTARAYEKSGVEAALSEAFHEEYSRLYQLAKETPTSHSDPRLQHVLVYFFQNEAPKRVVERTLLEQFADKNLSYDERSISIMKVAQAKLKEIGPDDMNMEEYKRWHEDYSLFRKVSVYLLTGLELYQKGKYQEALSYLVYAYQSNAALLMKGPRRGVKESVIALYRRKCLLELNAKAASLFETNDDHSVTEGINVMNELIIPCIHLIINNDISKDDLDAIEVMRNHWCSYLGQDIAENLQLCLGEFLPRLLDPSAEIIVLKEPPTIRPNSPYDLCSRFAAVMESIQGVSTVTVKSEQ ID NO:2753044 bpNOV96b,CGTAGGCGCTTCGGCCATGACTGCGGAGCTGCAGCAGGACGACGCGGCCGGCGCGGCACG59708-02 DNA SequenceGACGGCCACGGCTCGAGCTGCCAAATGCTGTTAAATCAACTGAGAGAAATCACAGGCATTCAGGACCCTTCCTTTCTCCATGAAGCTCTGAAGGCCAGTAATGGTGACATTACTCAGGCAGTCAGCCTTCTCACTGATGAGAGAGTTAAGGAGCCCAGTCAAGACACTGTTGCTACAGAACCATCTGAAGTAGAGGGGAGTGCTGCCAACAAGGAAGTATTAGCAAAAGTTATAGACCTTACTCATGATAACAAAGATGATCTTCAGGCTGCCATTGCTTTGAGTCTACTGGAGTCTCCCAAAATTCAAGCTGATGGAAGAGATCTTAACAGGATGCATGAAGCAACCTCTGCAGAAACTAAACGCTCAAAGAGAAATATCATGTTTATGCAAGAGCTTCAGTATTTGTTTGCTCTAATGATGGGATCAAATAGAAAATTTGTAGACCCGTCTGCAGCCCTGGATCTATTAAAGGGAGCATTCCGATCATCTGAGGAACAGCAGCAAGATGTGAGTGAATTCACACACAAGCTCCTGGATTGGCTAGAGGACGCATTCCAGCTAGCTGTTAATGTTAACAGTCCCAGGAACAAATCTGAAAATCCAATGGTGCAGCTGTTCTATGGTACTTTCCTGACTGAAGGGGTTCGTGAAGGAAAACCCTTTTGTAACAATGAGACCTTCGGCCAGTATCCTCTTCAGGTAAACGGTTATCGCAACTTAGACGAGTGTTTGGAAGGGGCCATGGTGGAGGGTGATGTTGAGCTTCTTCCCTCCGATCACTCGGTGAAGTATGGACAAGAGCGTTGGTTTACAAAGCTACCTCCAGTGTTGACCTTTGAACTCTCAAGATTTGAGTTTAATCAGTCCCTTGGGCAGCCAGAGAAAATTCACAATAAGCTGGAATTTCCTCAGATTATTTATATGGACAGGTACATGTACAGGAGCAAGGAGCTTATTCGAAATAAGAGAGAGTGTATTCGAAAGTTGAAGGAGGAAATAAAAATTCTGCAGCAAAAATTGGAAAGGTATGTGAAATATGGCTCAGGCCCAGCTCCGTTCCCGCTCCCGGACATGCTGAAATATGTTATTGAATTTGCTAGTACAAAACCTGCCTCAGAAAGCTGTCCACCTGAAAGTGACACACATATGACATTACCACTTTCTTCAGTGCACTGCTCGGTTTCTGACCAGACATCCAAGGAAACTACAAGTACAGAAACCTCTTCTCAGGATGTTGAAAGTACCTTTTCTTCTCCTGAAGATTCTTTACCCAAGTCTAAACCACTGACATCTTCTCGGTCTTCCATGGAAATGCCTTCACAGCCAGCTCCACGAACAGTCACAGATGAGCAGATAAATTTTGTTAAGACCTGTCTTCAGACATGGAGGAGTGAGATTGAACAAGATATACAAGATTTAAAGACTTGTATTGCAAGTACTACTCAGACTATTGAACAGATGTACTGCGATCCTCTCCTTCGTCAGGTGCCTTATCGCTTGCATGCAGTTCTTGTTCATGAACGACAAGCAAATGCTGGACACTATTCGGCCTATATCTATAATCAACCCCGACAGAGCTGGCTCAAGTACAATGACATCTCTGTTACTGAATCTTCCTGGGAACAAGTTCAAAGAGATTCCTATGGAGGCCTGAGAAATGTTACTGCTTACTGTCTCATCTACATTAATCCCAAACTACCCTACTTCAATGCAGAGGCAGCCCCAACTGAATCAGATCAAATGTCAGAACTGGAAGCCCTATCTCTGGAACTCAAGCATTACATTCACGAGGATAACTGGCGGTTTGAGCAGGAAGTAGAGGAGTGGGAAGAAGAGCAGTCTTGCAAAATCCCTCAAATCGAGTCCTCCCCCAACTCCTCATCACAGGCCTACTCTACATCACAAGAGCCTTCAGTAGCCTCTTCTCATGGGGTTCGCTGCTTGTCATCTGAGCATGCTGTGATTGTAAAGGAGCAAACTGCCCAGGCTATTGCAAACACAGCCCGTGCCTATGAGAAGAGCGGTGTAGAAGCGGCACTGAGTGAGGCATTCCATGAAGAATACTCCAGGCTCTATCAGCTTGCCAAAGAGACCCCCACCTCTCACAGTGATCCTCGACTTCAGCATGTCCTTGTCTACTTTTTAAAAATCTTAGCTATGATCAAAGATCAATCAGCATTATGAAGGTGGCTCAAGCGAAACTGAAGGAAATTGGTCCAGATGACATGAATATGGAAGAGTACAAGAGGTGGCATGAAGATTATAGTTTGTTCCGAAAAGTGTCTGTGTATCTCCTAACAGGCCTAGAACTCTATCAAAAAGGAAAGTACCAAGAGGCACTTTCCTACCTGGTATATCCCTACCAGAGCAATGCTGCCCTGCTGATGAACCGGCCCCGCCGGCGGCTCAAAGAATCCGTCATTGCTTTATACCGAAGAAAATGCCTTCTCGAGCTGAATGCCAAAGCAGCTTCTCTTTTTGAAACAAATGACACCTTATCATTAATAATGACATTTCCAAGGATGATCTGGATGCCATTGAGGTCATGAGAAACCATTGGTCCTCTTACCTTGGGCAAGATATTGCAGAAAATCTGCAGCTGTGCCTAGGGGAGTTTCTACCCAGACTTCTAGATCCTTCTCCAGAAATCATCGTCTTGAAAGAGCCTCCAACTATTCGACCCAATTCTCCCTATGACCTATGTAGCCGATTTGCAGCTGTCATCGAGTCAATTCAGGGAGTTTCAACTGTCACAGTGAAATAAGCTCCCACATGTTCAAGGCCCATTCTGGTTCCTGGCTGCCTCCCTCTTGCACAGAAGTTCCTTGTCATACTGCTCACCTTGGGAAAAGGATTAGGTGGGCACAORF Start: ATG at 17ORF Stop: TAA at 2939SEQ ID NO:276974 aaMW at 110687.3 kDNOV96b,MTAELQQDDAAGAADGHGSSCQMLLNQLREITGIQDPSFLHEALKASNGDITQAVSLLCG59708-02 ProteinSequenceTDERVKBPSQDTVATEPSEVEGSAANKEVLAKVTDLTHDNKDDLQAAIALSLLESPKIQADGRDLNRMHEATSAETKRSKRNIMFMQELQYLFALMMGSNRKFVDPSAALDLLKGAFRSSEEQQQDVSEFTHKLLDWLEDAFQLAVNVNSPRNKSENPMVQLFYGTFLTEGVREGKPFCNNETFGQYPLQVNGYRNLDECLEGAMVEGDVELLPSDHSVKYGQERWFTKLPPVLTFELSRFEFNQSLGQPEKIHNKLEFPQIIYMDRYMYRSKELIRNKRECIRKLKEEIKILQQKLERYVKYGSGPARFPLPDMLKYVIEFASTKPASESCPPESDTHMTLPLSSVHCSVSDQTSKESTSTESSSQDVESTFSSPEDSLPKSKPLTSSRSSMEMPSQPAPRTVTDEEINFVKTCLQRWRSEIEQDIQDLKTCIASTTQTIEQMYCDPLLRQVPYRLHAVLVHEGQANAGHYWAYIYNQPRQSWLKYNDISVTESSWEEVERDSYGGLRNVSAYCLMYINAKLPYFNAEAAPTESDQMSEVEALSVELKHYIQEDNWRFEQEVEEWEEEQSCKIPQMESSPNSSSQGYSTSQEPSVASSHGVRCLSSEHAVIVKEQTAQAIANTARAYEKSGVEAALSEAFHEEYSRLYQLAKETPTSHSDPRLQHVLVYFFQNEAPKRVVERTLLEQFADKNLSYDERSISIMKVAQAKLKEIGPDDMNMEEYKRWHEDYSLFRKVSVYLLTGLELYQKGKYQEALSYLVYAYQSNAALLMKGPRRGVKESVIALYRRKCLLELNAKAASLFETNDDHSVTEGINVMNELIIPCIHLIINNDISKDDLDAIEVMRNHWCSYLGQDIAENLQLCLGEFLPRLLDPSAEIIVLKEPPTIRPNSPYDLCSRFAAVMESIQGVSTVTVKSEQ ID NO:2773231 bpNOV96c,GCGCTTCGGCCATGACTGCGGAGCTGCAGCAGGACGACGCGGCCGGCGCGGCAGACGGCG59708-03 DNA SequenceCCACGGCTCGAGCTGCCAAATGCTGTTAAATCAACTGAGAGAAATCACAGGCATTCAGGACCCTTCCTTTCTCCATGAAGCTCTGAGGGCCAGTAATGGTGACATTACTCAGGCAGTCAGCCTTCTCACTGATGAGAGAGTTAAGGAGCCCAGTCAAGACACTGTTGCTACAGAACCATCTGAAGTAGAGGGGAGTGCTGCCAACAAGGAAGTATTAGCAAAAGTTATAGACACCATCTGAAGTAGAGGGGAGTGCTGCCAACAAGGAAGTATTAGCAAAAGTTATAGACCTTACTCATGATAACAAAGATGATCTTCAGGCTGCCATTGCTTTGAGTCTACTGGAGTCTCCCAAAATTCAAGCTGATGGAAGAGATCTTAACAGGATGCATGAAGCAACCTCTGCAGAAACTAAACGCTCAAAGAGAAAACGCTGTGAAGTCTGGGGAGAAAACCCCAATCCCAATGACTGGAGGAGAGTTGATGGTTGGCCAGTTGGGCTGAAAAATGTTGGCAATACATGTTGGTTTAGTGCTGTTATTCAGTCTCTCTTTCAATTGCCTGAATTTCGAAGACTTGTTCTCAGTTATAGTCTGCCACAAAATGTACTTGAAAATTGTCGAAGTCATACAGAAAAGAGAAATATCATGTTTATGCAAGAGCTTCAGTATTTGTTTGCTCTAATGATGGGATCAAATAGAAAATTTGTAGACCCGTCTGCAGCCCTGGATCTATTAAAGGGAGCATTCCGATCATCTGAGGAACAGCAGCAAGATGTGAGTGAATTCACACACAAGCTCCTGGATTGGCTAGAGGACGCATTCCAGCTAGCTGTTAATGTTAACAGTCCCAGGAACAAATTTGAAAATCCAATGGTGCAGCTGTTCTATGGTACTTTCCTGACTGAAGGGGTTCGTGAAGGAAAACCCTTTTGTAACAATGAGACCTTCGCCCAGTATCCTCTTCAGCTAAACGGTTATCCCAACTTAGACGAGTGTTTCGAAGGGGCCATGGTGGAGGCTGATGTTGAGCTTCTTCCCTCCGATCACTCGGTGAAGTATGGACAAGAGCGTTGGTTTACAAAGCTACCTCCAGTGTTGACCTTTGAACTCTCAACATTTGAGTTTAATCAGTCCCTTGGGCAGCCAGAGAAAATTCACAATAAGCTGGAATTTCCTCAGATTATTThTATGGACAQGTACATGTACAGGAGCAAGGGCAGCAAAAATTGGAAGGGTATGTGAAATATGGCTCAGGCCCAGCTCGGTTCCCGCTCCCGGACATGCTCAAATATCTTATTGAATTTCCTAGTACAAAACCTGCCTCAGAAAGCTGTCCACCTGAAACTGACACACATATGACATTACCACTTTCTTCAGTGCACTGCTCGCTAGTACCTTTTCTTCTCCTGAAGATTCTTTACCCAAGTCTAAACCACTGACATCTTCTCGGTCTTCCATGGAAATGCCTTCACAGCCAGCTCCACGAACACTCACAGATGAGGAGATAAATTTTGTTAAGACCTGTCTTCAGAGATGCAGCAGTGAGATTCAACAAGATATACAAGATTTAAAGACTTGTATTGCAAGTACTACTCAGACTATTCAACAGATGTACTGCGATCCTCTCCTTCGTCAGGTGCCTTATCGCTTGCATGCAGTTCTTGTTCATCAAGGACAAGCAAATGCTGGACACTATTGGGCCTATATCTATAATCAACCCCGACAGAGCTGCCTCAAGTACAATGACATCTCTCTTACTGAATCTTCCTGGGAACAAGTTGAAAGAGATTCCTATGCACCCCTGAGAAATGTTACTGCTTACTGTCTGATGTACATTAACGACAAACTACCCTACTCATCACAGGACTACTCTACATCACAAGAGCCTTCAGTACCCTCTTCTCATGGGCTTCGCTGCTTCTCATCTGAGCATGCTGTGATTGTAAAGGAGCAAACTGCCCAGGCTATTGCAAACACAGCCCGTGCCTATGAGAAGAGCCGTGTACAAGCGGCACTCAGTGAGGCATTCCATGAACAATACTCCAGGCTCTATCAGCTTGCCAAAGAGACCCCCACCTCTCACAGTGATCCTCGACTTCAGCATGTCCTTGTCTACTTTTTCCAAAATGAAGCACCCAAAAGGGTAGTAGAACGAACCCTTCTGGAACAGTTTGCAGATAAAAATCTTAGCTATGATGAAAGATGAATATGGAAGAGTACAAGAAGTGGCATGAAGATTATAGTTTGTTCCGAAAAGTGTCTGTGTATCTCCTAACAGGCCTAGAACTCTATCAAAAAGGAAAGTACCAAGAGGCACTTTCCTACCTGGTATATGCCTACCAGAGCAATGCTGCCCTGCTGATGAAGGGGCCCCCCCGGGGGGTCAAACAATCCGTGATTGCTTTATACCGAAGAAAATGCCTTCTGCAGCTGAATGCCAAAGCAGCTTCTCTTTTTGAAACAAATGATGATCACTCCGTAACTGAGGGCATTAATGTGATGAATGAACTGATCATCCCCTGCATTCACCTTATCATTAATAATGACATTGGCAAGATATTGCAGAAAATCTGCAGCTGTGCCTAGGGGAGTTTCTACCCAGACTTCTAGATCCTTCTGCAGAAATCATCCTCTTGAAAGAGCCTCCAACTATTCGACCCAATTCTCCCTATGACCTATGTAGCCGATTTCCAGCTGTCATGGAGTCAATTCAGGGAGTTTCAACTGTGACACTGAAATAAGCTCCCACATGTTCAAGCCCCATTCTGGTTCCTGGCTGCCTGCCTCTTGCACAGAACTTCCTTGTCATAGTGCTCACCTTGGORF Start: ATG at 12ORF Stop: TAA at 3147SEQ ID NO:2781045 aaMW at 119107.7 kDNOV96c,MTAELQQDDAAGAADGHGSSCQMLLNQLREITGIQDPSFLHEALKASNGDITQAVSLLCG59708-03 ProteinSequenceTDERVKBPSQDTVATEPSEVEGSAANKEVLAKVTDLTHDNKDDLQAAIALSLLESPKIQADGRDLNRMHEATSAETKRSKRKRCEVWGENPNPNDWRRVDGWPVGLKNVGNTCWFSAVIQSLFQLPEFRRLVLSYSLPQNVLENCRSHTEKRNIMFMQELQYLFALMMGSNRKFVDPSAALDLLKGAFRSSEEQQQDVSEFTHKLLDWLEDAFQLAVNVNSPRNKSENPMVQLFYGTFLTEGVREGKPFCNNETFGQYPLQVNGYRNLDECLEGAMVEGDVELLPSDHSVKYGQERWFTKLPPVLTFELSRFEFNQSLGQPEKIHNKLEFPQIIYMDRYMYRSKELIRNKRECIRKLKEEIKILQQKLERYVKYGSGPARFPLPDMLKYVIEFASTKPASESCPPESDTHMTLPLSSVHCSVSDQTSKESTSTESSSQDVESTFSSPEDSLPKSKPLTSSRSSMEMPSQPAPRTVTDEEINFVKTCLQRWRSEIEQDIQDLKTCIASTTQTIEQMYCDPLLRQVPYRLHAVLVHEGQANAGHYWAYIYNQPRQSWLKYNDISVTESSWEEVERDSYGGLRNVSAYCLMYINAKLPYFNAEAAPTESDQMSEVEALSVELKHYIQEDNWRFEQEVEEWEEEQSCKIPQMESSPNSSSQGYSTSQEPSVASSHGVRCLSSEHAVIVKEQTAQAIANTARAYEKSGVEAALSEAFHEEYSRLYQLAKETPTSHSDPRLQHVLVYFFQNEAPKRVVERTLLEQFADKNLSYDERSISIMKVAQAKLKEIGPDDMNMEEYKRWHEDYSLFRKVSVYLLTGLELYQKGKYQEALSYLVYAYQSNAALLMKGPRRGVKESVIALYRRKCLLELNAKAASLFETNDDHSVTEGINVMNELIIPCIHLIINNDISKDDLDAIEVMRNHWCSYLGQDIAENLQLCLGEFLPRLLDPSAEIIVLKEPPTIRPNSPYDLCSRFAAVMESIQGVSTVTVK


[0828] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 96B.
504TABLE 96BComparison of NOV96a against NOV96b through NOV96c.Identities/ProteinNOV96a Residues/Similarities forSequenceMatch Residuesthe Matched RegionNOV96b209 . . . 1045805/837 (96%)138 . . . 974805/837 (96%)NOV96c 1 . . . 1045979/1045 (93%) 1 . . . 1045981/1045 (93%)


[0829] Further analysis of the NOV96a protein yielded the following properties shown in Table 96C.
505TABLE 96CProtein Sequence Properties NOV96aPSort0.8800 probability located in nucleus; 0.3000 probabilityanalysis:located in microbody (peroxisome); 0.1000 probability locatedin mitochondrial matrix space; 0.1000 probability located inlysosome (lumen)SignalPNo Known Signal Sequence Predictedanalysis:


[0830] A search of the NOV96a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 96D.
506TABLE 96DGeneseq Results for NOV96aNOV96aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAE04874Human protease protein-1 (PRTS-22 . . . 1036524/1035 (50%)0.01) Homo sapiens, 1055 aa.18 . . . 1047713/1035 (68%)[WO200146443-A2,28 JUN. 2001]AAB31552A human ubiquitin specific22 . . . 1036524/1035 (50%)0.0protease 25 (USP25)-Homo18 . . . 1047713/1035 (68%)sapiens, 1055 aa. [WO200079267-A2, 28 DEC. 2000]AAB31546A human ubiquitin specific22 . . . 1036524/1035 (50%)0.0protease 25 (USP25)-Homo18 . . . 1047713/1035 (68%)sapiens, 1055 aa. [WO200078934-A2, 28 DEC. 2000]AAB74491Human SYK kinase binding22 . . . 1036522/1035 (50%)0.0protein sapiens, 1055 aa.18 . . . 1047710/1035 (68%)[WO200121654-A2,29 MAR. 2001]AAB31556A human ubiquitin specific22 . . . 1036525/1067 (49%)0.0protease (USP)-Homo sapiens,18 . . . 1079717/1067 (66%)1087 aa. [WO200079267-A2,28 DEC. 2000]


[0831] In a BLAST search of public sequence databases, the NOV96a protein was found to have homology to the proteins shown in the BLASTP data in Table 96E.
507TABLE 96EPublic BLASTP Results for NOV96aNOV96aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueQ96RU2UBIQUITIN SPECIFIC PROTEASE- 1 . . . 10451041/1077 (96%)0.0Homo sapiens (Human), 1077 aa. 1 . . . 10771042/1077 (96%)Q9P213KIAA1515 PROTEIN-Homo304 . . . 1045 738/742 (99%)0.0sapiens (Human), 757 aa (fragment). 16 . . . 757 739/742 (99%)P57080Ubiquitin carboxyl-terminal 22 . . . 1036 527/1033 (51%)0.0hydrolase 25 (EC 3.1.2.15) 18 . . . 1047 710/1033 (68%)(Ubiquitin thiolesterase 25)(Ubiquitin-specific processingprotease 25) (Deubiquitinatingenzyme 25) (mUSP25)-Musmusculus (Mouse), 1055 aa.Q9UHP3Ubiquitin carboxyl-terminal 22 . . . 1036 525/1067 (49%)0.0hydrolase 25 (EC 3.1.2.15) 18 . . . 1079 717/1067 (66%)(Ubiquitin thiolesterase 25)(Ubiquitin-specific processingprotease 25) (Deubiquitinatingenzyme 25) (USP on chromosome21)-Homo sapiens (Human), 1087aa.Q9H9W1CDNA FLJ12512 FIS, CLONE313 . . . 1036363/733 (49%)0.0NT2RM2001730, WEAKLY 2 . . . 729510/733 (69%)SIMILAR TO PROBABLEUBIQUITIN CARBOXYL-TERMINAL HYDROLASEK02C4.3 (EC 3.1.2.15)-Homosapiens (Human), 737 aa.


[0832] PFam analysis predicts that the NOV96a protein contains the domains shown in the Table 96F.
508TABLE 96FDomain Analysis of NOV96aIdentities/PfamNOV96aSimilarities forExpectDomainMatch Regionthe Matched RegionValueUIM: domain 1 of 1 96 . . . 113 9/18 (50%)8.414/18 (78%)UCH-1: domain 1 of 1162 . . . 19314/32 (44%)2.6e−1128/32 (88%)UCH-2: domain 1 of 1580 . . . 64926/72 (36%)1.5e−1956/72 (78%)



Example 97

[0833] The NOV97 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 97A.
509TABLE 97ANOV97 Sequence AnalysisSEQ ID NO:2791601 bpNOV97a,AGGGCAGAGGCCACAGCGCCATCCCCTTCCCCATGGTCTCCCTACCCCCAACCTGCACCG59559-01 DNA SequenceTGGGCGCTCCGCCCAGAGGTGAGTCCCTCCCAGCCCTTCTCTCCTTCTGTCCTAGCCATCCGCAGAGCCATCCTCTGCAAAGGAAGGAGCTAGGCTGTGCGCCCTGGGCCTCATGAGGGGGACTCTGTGCATAGGGCAGTATACAAGGACCTGGTGCTTCTGCTGCAGAAGGACCGCCTGCTCACTCCCGGGCAGCTTAGAGCAAGGGGGCAGCTGAACTTCGAACAAGATGAGCTGGTGGACGGAGGCCAGCGGGGCCACATGCACAACGGCCTTAACTACCGTGAGGTCCGCGAGTTCCGCTCCGACCACCATCTGCTACGTTTTTACTTCCTCACCCGCGTGTACTCCCATTACCTCCAGACCATCTTGAAAGAGCTGCAGTCGGGCGAGCACGCCCCCGACCTGGTCATCATGAATTCCTGCCTCTGGGACATCTCCAGGTATGGTCCGAACTCCTGGAGAAGCTACCTCGAGAACCTGGAGAACCTGTTCCAGTCCCTGGGCCAGGTGCTGCCCGAGTCTTGCCTCCTGGTGTGGAACACGGCCATGCCTGTGGGCGAGGAAGTCACCGGGGGTTTTCTTCCGCCCAAGCTCCGGCGGCACAAGGCCACCTTCCTGAAAAACGAAGTGGTCAAAGCCAACTTCCACAGCGCCACCGACGCACGTAAACATAACTTCGATGTACTGGACTTGCATTTCCACTTCCCCCACGCGAGGGAGAACCTGCACTGGGACGGGGTGCACTGGAATGGACGTGTGCACCGCTGCCTCTCCCAGCTGCTGCTGGCCCACGTGGCCGACGCCTGGGGTGTGGACCTGCCCCACCGCCACCCCGTGGGCGAGTGGATCAAGAAGAAAAAACCTGGCCCGAGAGTCGAAGGGCCGCCCCAGGCCAACAGAAATCACCCGGCCTTACCTCTGTCCCCACCCTTACCTTCCCCCACATACCGCCCCCTGCTTGGGTTCCCACCCCAGCGCTTGCCGCTGCTCCCGCTCCTGTCCCCACAGCCTCCTCCTCCCATTCTCCATCACCAGGGAATGCCCCGGTTCCCACACGGTCCCCCAGATGCCTGTTTTTCCTCAGACCATACTTTCCAGTCGCATCAATTCTATTGCCATTCAGATGTCCCCTCATCAGCCCATGCAGGTTTCTTCGTCGAAGACAATTTTATGGTTGGTCCTCAGCTGCCTATGCCCTTCTTCCCCACACCCCGTTATCAGCGGCCTGCCCCAGTGGTACATAGGGGTTTTGGCAGGTATCGTCCCCGTGGCCCCTATACGCCCTGGGGACAGCGGCCTCGACCTTCAAAGAGAAGGGCCCCAGCCAATCCTGAGCCAAGGCCTCAATAGACGGACCTAGGCCTTATTTCCTCTTTATGAACATGGATTGGACAGATCTGACACTTCCTTTCCATTGCTTCGCCTGAACAGACTGACCTTGTTAACTTAAGCCTCCAGTCCATGCCTCGTCTTCCTTTTGTTORF Start: ATG at 171ORF Stop: TAG at 1467SEQ ID NO:280432 aaMW at 49726.6 kDNOV97a,MILLRASEVRQLLHNKFVVILGDSVHRAVYKDLVLLLQKDRLLTPGQLRARGELNFEQCG59559-01 Protein SequenceDELVDGGQRGHMHNGLNYREVREFRSDHHLVRFYFLTRVYSDYLQTILKELQSGEHAPDLVIMNSCLWDISRYGPNSWRSYLENLENLFQCLGQVLPESCLLVWNTAMPVGEEVTGGFLPPKLRRQKATFLKNEVVKANFHSATEARKHNFDVLDLHFHFRHARENLHWDGVHWNGRVHRCLSQLLLAHVADAWGVELPHRHPVGEWIKKKKPGPRVEGPPQANRNHPALPLSPPLPSPTYRPLLGFPPQRLPLLPLLSPQPPPPILHHQGMPRFPQGPPDACFSSDHTFQSDQFYCHSDVPSSAHAGFFVEDNFMVGPQLPMPFFPTPRYQRPAPVVHRGFGRYRPRGPYTPWGQRPRPSKRRAPANPEPRPQ


[0834] Further analysis of the NOV97a protein yielded the following properties shown in Table 97B.
510TABLE 97BProtein Sequence Properties NOV97aPSort0.5937 probability located in mitochondrial matrix space;analysis:0.5103 probability located in microbody (peroxisome); 0.4900probability located in nucleus; 0.3252 probability located inlysosome (lumen)SignalPNo Known Signal Sequence Predictedanalysis:


[0835] A search of the NOV97a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 97C.
511TABLE 97CGeneseq Results for NOV97aNOV97aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAG74241Human colon cancer antigen protein34 . . . 294162/268 (60%)1e−82SEQ ID NO: 5005-Homo sapiens, 1 . . . 266191/268 (70%)281 aa. [WO200122920-A2,5 APR. 2001]AAE03639Human extracellular matrix and cell 1 . . . 421197/435 (45%)2e−82adhesion molecule-3 (XMAD-3)- 1 . . . 366231/435 (52%)Homo sapiens, 386 aa.[WO200142285-A2, 14 JUN. 2001]


[0836] In a BLAST search of public sequence databases, the NOV97a protein was found to have homology to the proteins shown in the BLASTP data in Table 97D.
512TABLE 97DPublic BLASTP Results for NOV97aNOV97aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueQ96HM7SIMILAR TO HYPOTHETICAL 1 . . . 432432/432 (100%)0.0PROTEIN FLJ22376-Homo sapiens 1 . . . 432432/432 (100%)(Human), 432 aa.Q96B20HYPOTHETICAL 31.4 KDA121 . . . 310190/190 (100%) e−116PROTEIN-Homo sapiens (Human), 1 . . . 190190/190 (100%)279 aa.Q9H1Q7BA12M19.1.3 (NOVEL PROTEIN) 1 . . . 421234/437 (53%) e−111(CDNA FLJ31791 FIS, CLONE 18 . . . 434273/437 (61%)NT2RI2008749, WEAKLYSIMILAR TO SPLICEOSOMEASSOCIATED PROTEIN 49)-Homo sapiens (Human), 454 aa.Q9H1Q6BA12M19.1.1 (NOVEL PROTEIN)- 1 . . . 421197/435 (45%)7e−82Homo sapiens (Human), 403 aa. 18 . . . 383231/435 (52%)Q9H6D1CDNA: FLJ22376 FIS, CLONE 1 . . . 421196/435 (45%)1e−81HRC07327-Homo sapiens 18 . . . 383231/435 (53%)(Human), 403 aa.


[0837] PFam analysis predicts that the NOV97a protein contains the domains shown in the Table 97E.
513TABLE 97EDomain Analysis of NOV97aIdentities/PfamNOV97aSimilarities forExpectDomainMatch Regionthe Matched RegionValueNo Significant Matches Found


[0838] The NOV98 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 98A.
514TABLE 98ANOV98 Sequence AnalysisSEQ ID NO:281981 bpNOV98a,GCGCCGGGTCCCAGAATCTAGTCCTACGCCACGGTTTTGACCACGCGTGACCCGCTGCCG59669-01 DNA SequenceCCAGCCGGCCCGGCCATCAGGTGGTCCGTGTGTCCCTCTGACATGTCGTCCTGCAGCCGCGTGGCCCTGGTAACTGGGGCTAACAAAGGCATCGGCTTTGCGATCACGCGTGACCTGTGTCGGAAATTCTCCGGGGACGTGGTGCTCACGGCGCGGGACGAGGCGCGGGGCCGCGCGGCGGTGCAGCAGCTGCAGGCGGAGGGCCTGAGCCCACGCTTCCACCAGCTGGACATCGACGACCCGCAGAGCATCCGTGCGCTGCGCGACTTTCTGCGCAAGGAGTACGGGGGACTTAACGTGCTGGTCAACAACGCGGGCATCGCCTTTAGAAGTACTGATCTCACCCACTTTCACATTCTAAGAGAAGCTGCAATGAAAACTAACTTTTTTGGTACCCAGGCCGTCTGCACAGAGCTACTCCCTCTAATAAAAACCCAAGGTAGAGTGGTGAATATATCAAGCCTAATAAGTCTAGAGGCCCTGAAAAACTGCAGCCTGGAGCTACAGCAGAAGTTTCGAAGTGAGACCATCACAGAGGAGGAGCTGGTGGGGCTCATGAACAAGTTTGTGGAGGATACAAAGAAAGGAGTCCATGCAAAAGAAGGCTGGCCTAATAGTGCATACGGGGTGTCTAAGATTGGAGTGACAGTCCTGTCCAGAATCCTTGCCAGGAAACTCAATGAGCAGAGGAGAGGGGACAAGATCCTTCTGAATGCCTGCTGCCCTGGCTGGGTCAGAACCGACATGGCAGGACCACAAGCCACCAAAAGCCCAGAAGAAGGAGCAGAGACCCCTGTGTACTTGGCCCTTTTGCCTCCAGATGCAGAGGGACCTCATGGGCAGTTTGTTCAAGATAAAAAAGTGGAACAATGGTGAACTCAGCTCTTTGTACAGCTCCCATCTGTAGCCTGTCCTAAAGGGGAORF Start: ATG at 101ORF Stop: TGA at 932SEQ ID NO:282277 aaMW at 30547.7 kDNOV98a,MSSCSRVALVTGANKGIGFAITRDLCRKFSGDVVLTARDEARGRAAVQQLQAEGLSPRCG59669-01 Protein SequenceFHQLDIDDPQSIRALRDFLRKEYGGLNVLVNNAGIAFRSTDLTHFHILREAAMKTNFFGTQAVCTELLPLIKTQGRVVNISSLISLEALKNCSLELQQKFRSETITEEELVGLMNKFVEDTKKGVHAKEGWPNSAYGVSKIGVTVLSRILARKLNEQRRGDKILLNACCPGWVRTDMAGPQATKSPEEGAETPVYLALLPPDAEGPHGQFVQDKKVEQW


[0839] Further analysis of the NOV98a protein yielded the following properties shown in Table 98B.
515TABLE 98BProtein Sequence Properties NOV98aPSort0.4766 probability located in mitochondrial matrix space;analysis:0.4500 probability located in cytoplasm; 0.1822 probabilitylocated in mitochondrial inner membrane; 0.1822 probabilitylocated in mitochondrial intermembrane spaceSignalPNo Known Signal Sequence Predictedanalysis:


[0840] A search of the NOV98a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 98C.
516TABLE 98CGeneseq Results for NOV98aNOV98aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAW51011Human liver carbonyl reductase- 1 . . . 277236/277 (85%) e−134Homo sapiens, 277 aa. 1 . . . 277252/277 (90%)[U.S. Pat. No. 5756299-A,26 MAY 1998]AAU33100Novel human secreted protein142 . . . 277119/136 (87%)2e−66#3591-Homo sapiens, 175 aa. 39 . . . 174128/136 (93%)[WO200179449-A2, 25 Oct. 2001]AAM73641Human bone marrow expressed 1 . . . 97 86/97 (88%)7e−43probe encoded protein SEQ ID NO: 1 . . . 97 92/97 (94%)33947-Homo sapiens, 123 aa.[WO200157276-A2, 9 AUG. 2001]AAM60948Human brain expressed single exon 1 . . . 97 86/97 (88%)7e−43probe encoded protein SEQ ID NO: 1 . . . 97 92/97 (94%)33053-Homo sapiens, 123 aa.[WO200157275-A2, 9 AUG. 2001]AAM33832Peptide #7869 encoded by probe for 1 . . . 97 86/97 (88%)7e−43measuring placental gene expression- 1 . . . 97 92/97 (94%)Homo sapiens, 123 aa.[WO200157272-A2, 9 AUG. 2001]


[0841] In a BLAST search of public sequence databases, the NOV98a protein was found to have homology to the proteins shown in the BLASTP data in Table 98D.
517TABLE 98DPublic BLASTP Results for NOV98aNOV98aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueQ924V2CARBONYL REDUCTASE 2-1 . . . 277243/277 (87%)e−139Cricetulus griseus (Chinese1 . . . 277260/277 (93%)hamster), 277 aa.Q91X28SIMILAR TO CARBONYL1 . . . 277244/277 (88%)e−139REDUCTASE 1-Mus musculus1 . . . 277256/277 (92%)(Mouse), 277 aa.Q924V3CARBONYL REDUCTASE 1-1 . . . 277241/277 (87%)e−137Cricetulus griseus (Chinese1 . . . 277256/277 (92%)hamster), 277 aa.P48758Carbonyl reductase [NADPH] 1 (EC2 . . . 277240/276 (86%)e−1361.1.1.184) (NADPH-dependent1 . . . 276253/276 (90%)carbonyl reductase 1)-Musmusculus (Mouse), 276 aa.JC5284carbonyl reductase (NADPH) (EC1 . . . 277236/277 (85%)e−1341.1.1.184), inducible-rat, 277 aa.1 . . . 277249/277 (89%)


[0842] PFam analysis predicts that the NOV98a protein contains the domains shown in the Table 98E.
518TABLE 98EDomain Analysis of NOV98aIdentities/PfamNOV98aSimilarities forExpectDomainMatch Regionthe Matched RegionValueadh_short: domain 14 . . . 274 67/286 (23%)1.6e−38of 1185/286 (65%)



Example 99.

[0843] The NOV99 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 99A.
519TABLE 99ANOV99 Sequence AnalysisSEQ ID NO:2831001 bpNOV99a,CTTGGTATAAGTAAGTGCTCGTCAATGTTGGCTACTCTCAATGTCAGAGCCGCAGCCGCG58624-01 DNA SequenceCGGGGCGCAGAGCGCGATCTCTACCGGGACACGTGGGTGCGATACCTGGGCTATGCCAATGAGGTGGGCGAGGCTTTCCGCTCTCTTGTGCCAGCGGCGGTGGTGTGGCTGAGCTATGGCGTGGCCAGCTCCTACGTGCTGGCGGATGCCATTGACAAAGGCAAGAAGGCTGGAGAGGTGCCCAGCCCTGAAGCAGGCCGCAGCGCCAGGGTGACTGTGGCTGTGGTGGACACCTTTGTATGGCAGGCTCTAGCCTCTGTGGCCATTCCGGGCTTCACCATCAACCGCGTGTGTGCTGCCTCTCTCTATGTCCTGGGCACTGCCACCCGCTGGCCCCTGGCTGTCCGCAAGTGGACCACCACCGCGCTTGGGCTGTTGACCATCCCCATCATTATCCACCCCATTGACAGGGATCATCCACTCTCCAGTGATGAGAGTGGATCATCCAGTCTCCAGCACGAAGGGCCAGGGGTCCCACAGGTGAGTGGAGCCCCAGCAGCCCCCTCAGCTCTGCGTGCCCATGTACTGGTCTTCTCCCTGGCTCTATACTCAGTGTTCAAGGGGTTGGACGGGGCTTGGGCCGCGGAGCTGCGCCTGGCTTTGCTGCTCCACAAGGGCACCGTGGCTGTCAGCCTGTCCCTGCAACTGCTGCAGAGCCACGTAGGGTTACAGGTGGTGGCTGGCTGTGGGATCCACTTCTTGTGCATGACACTTCTAGGCATCCGGCTGGGTGCGGCTCTGGCACAGTCAGCAGGGCCTCTGCACCAGCTGGCCCAGTCTGTGCTAGAGGGCATGGTGGCTGGCACCTTCCTGTATACCACCTTTCTGGAAATCTTTCCACAGGAGCTGGCGACTTCTGAGCAAAGGATCCTCAAGGTCATTCTGCTCCTAGAAGGGTGTGCCCTGCTCACTGGCCTGCTCTTCATCCATATCTAGGGGGCTTORF Start: ATG at 41ORF Stop: TAG at 992SEQ ID NO:284317aaMW at 33737.8 kDNOV99a,MSEPQPRGAERDLYRDTWVRYLGYANEVGEAFRSLVPAAVVWLSYGVASSYVLADAIDCG58624-01 Protein SequenceKGKKAGEVPSPEAGRSARVTVAVVDTFVWQALASVAIPGFTINRVCAASLYVLGTATRWPLAVRKWTTTALGLLTIPIIIHPIDRDHPLSSDESGSSSLQHEGPGVPQVSGAPAAPSALRAHVLVFSLALYSVFKGLDGAWAAELRLALLLHKGTVAVSLSLQLLQSHVGLQVVAGCGIHFLCMTLLGIRLGAALAQSAGPLHQLAQSVLEGMVAGTFLYTTFLEIFPQELATSEQRILKVILLLEGCALLTGLLFIHI


[0844] Further analysis of the NOV99a protein yielded the following properties shown in Table 99B.
520TABLE 99BProtein Sequence Properties NOV99aPSort0.6000 probability located in plasma membrane;analysis:0.4000 probability located in Golgi body; 0.3000probability located in endoplasmic reticulum (membrane);0.1000 probability located in mitochondrial inner membraneSignalPLikely cleavage site between residues 55 and 56analysis:


[0845] A search of the NOV99a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 99C.
521TABLE 99CGeneseq Results for NOV99aNOV99aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAM93835Human polypeptide, SEQ ID NO:140 . . . 317134/184 (72%)3e−633905-Homo sapiens, 324 aa.141 . . . 324145/184 (77%)[EP1130094-A2, 5 SEP. 2001]AAY52394Human transmembrane protein140 . . . 317134/184 (72%)3e−63HP10528-Homo sapiens, 324 aa.141 . . . 324145/184 (77%)[WO9955862-A2, 4 NOV. 1999]AAY84895A human proliferation and140 . . . 317134/184 (72%)3e−63apoptosis related protein-Homo141 . . . 324145/184 (77%)sapiens, 324 aa. [WO200023589-A2, 27 APR. 2000]AAB43291Human ORFX ORF3055140 . . . 317134/184 (72%)3e−63polypeptide sequence SEQ ID140 . . . 323145/184 (77%)NO: 6110-Homo sapiens, 323 aa.[WO200058473-A2, 5 OCT. 2000]AAM93650Human polypeptide, SEQ ID NO:140 . . . 317133/184 (72%)2e−623514-Homo sapiens, 324 aa.141 . . . 324144/184 (77%)[EP1130094-A2, 5 SEP. 2001]


[0846] In a BLAST search of public sequence databases, the NOV99a protein was found to have homology to the proteins shown in the BLASTP data in Table 99D.
522TABLE 99DPublic BLASTP Results for NOV99aNOV99aIdentities/ProteinResidues/SimilaritiesAccessionMatchfor theExpectNumberProtein/Organism/LengthResiduesMatched PortionValueQ9UDX5WUGSC:H_DJ0539M06.2 PROTEIN - 1 . . . 152145/152 (95%)6e−78Homo sapiens (Human), 166 aa. 1 . . . 152145/152 (95%)Q9CRB82610507A21RIK PROTEIN 1 . . . 168133/168 (79%)8e−69(1700020C11RIK PROTEIN) - Mus 1 . . . 164143/168 (84%)musculus (Mouse), 166 aa.Q9CZX42610507A21RIK PROTEIN - Mus 1 . . . 143125/143 (87%)2e−68musculus (Mouse), 166 aa. 1 . . . 143133/143 (92%)Q9NY26IRT1 PROTEIN (SIMILAR TO140 . . . 317134/184 (72%)1e−62ZINC/IRON REGULATED141 . . . 324145/184 (77%)TRANSPORTER-LIKE)(HYPOTHETICAL 34.2 KDAPROTEIN) (UNKNOWN) (PROTEINFOR MGC:14180) - Homo sapiens(Human), 324 aa.Q9Y380CGI-71 PROTEIN - Homo sapiens140 . . . 317134/184 (72%)1e−62(Human), 324 aa.141 . . . 324145/184 (77%)


[0847] PFam analysis predicts that the NOV99a protein contains the domains shown in the Table 99E.
523TABLE 99EDomain Analysis of NOV99aIdentities/SimilaritiesNOV99a Matchfor theExpectPfam DomainRegionMatched RegionValueSyndecan: domain 1 of 1235 . . . 2559/21(43%)6.916/21(76%)Zip: domain 1 of 1174 . . . 31352/178(29%)2.3e−15108/178(61%)



Example 100

[0848] The NOV100 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 100A.
524TABLE 100ANOV100 Sequence AnalysisSEQ ID NO:285987 bpNOV100a,AGACGCTCACACAGACAACCTCAAGTCCAGCAACATCTTAGTAGCCCAAAATCGACTGCG59679-01 DNA SequenceCTTTAGTTCTTCTGGTGGGTGCCTCTCACTGTCCACTCGGCTATGCCATCCTGCAGTCGCATTGCACTGGTGACTGGAGCTAATAAGGGCATTGGCTTTGCGATCACTCGTGACCTGTGTCAGCAATTCTCAGGGGATGTGGTGCTCACTGCACGGGACGAGGCACGGGGCCTTGCGGCAGTGCAGAAGCTGCAGGCTGAGGGCCTGATTCCTCGCTTCCACCAGCTGGACATCAATGACCCTCAGAGCATCCATGCACTTCGCAACTTTCTGCTCAAGGAGTACGGAGGCCTGGATGTGCTGGTCAACAACGCGGGCATTGGCGTGCTTTTCAAAGTGGATGACCCAACACCCTTCGACATTCAAGCTGAGGTGACACTGAAGACGAACTTTTTTGCCACTAGAAATGTCTGCACTGAGTTACTGCCTATAATGAAACCACATGGTAGAGTGGTGAACATCAGCAGTCTGCAGGGGTTAAAAGCCCTTGAGAACTGCAGGGAAGATCTTCAGGAAAAGTTCCGATGTGACACACTTACCGAGGTGGACCTGGTCGACCTCATGAAAAAGTTTGTGGAGGATACAAAAAATGAAGTCCATGAGAGGGAAGGTTGGCCAGACTCGGCTTACGGGGTGTCGAAGCTGGGGGTGACAGTCCTTACGAGGATCCTGGCCCGGCAGCTGGATGAAAAGAGGAAAGCGGACAGGATTCTGCTCAATGCCTGCTGCCCGGGATGGGTGAAGACCGACATGGCGAGGGACCAGGGCTCCCGGACCGTGGAAGAGGGGGCCGAAACCCCCGTTTACTTGGCTCTCCTGCCTCCAGATGCCACTGAACCTCACGGCCAGCTAGTCCGTGACAAAGTTGTGCAAACTTGGTGAACGTCTGCTCTGGGGCTTAATTGTTTGATAAACGTTAGCGGGAGAGAORF Start: ATG at 101ORF Stop: TGA at 938SEQ ID NO:286279 aaMW at 31007.2 kDNOV100a,MPSCSRIALVTGANKGIGFAITRDLCQQFSGDVVLTARDEARGLAAVQKLQAEGLIPRCG59679-01 Protein SequenceFHQLDINDPQSIHALRNFLLKEYGGLDVLVNNAGIGVLFKVDDPTPFDIQAEVTLKTNFFATRNVCTELLPIMKPHGRVVNISSLQGLKALENCREDLQEKFRCDTLTEVDLVDLMKKFVEDTKNEVHEREGWPDSAYGVSKLGVTVLTRILARQLDEKRKADRILLNACCPGWVKTDMARDQGSRTVEEGAETPVYLALLPPDATEPHGQLVRDKVVQTW


[0849] Further analysis of the NOV100a protein yielded the following properties shown in Table 100B.
525TABLE 100BProtein Sequence Properties NOV100aPSort0.3600 probability located in mitochondrial matrix space;analysis:0.3000 probability located in microbody (peroxisome); 0.1808probability located in lysosome (lumen); 0.0000 probabilitylocated in endoplasmic reticulum (membrane)SignalPNo Known Signal Sequence Predictedanalysis:


[0850] A search of the NOV100a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 100C.
526TABLE 100CGeneseq Results for NOV100aNOV100aIdentities/Residues/SimilaritiesGeneseqProtein/Organism/LengthMatchfor theExpectIdentifier[Patent #, Date]ResiduesMatched RegionValueAAW51011Human liver carbonyl reductase - 1 . . . 279198/279(70%) e−112Homo sapiens, 277 aa. 1 . . . 277233/279(82%)[US5756299-A, 26 MAY 1998]AAU33100Novel human secreted protein145 . . . 27988/135(65%)2e−48#3591 - Homo sapiens, 175 aa. 40 . . . 174110/135(81%)[WO200179449-A2, 25 OCT2001]AAG46601Arabidopsis thaliana protein 3 . . . 259106/268(39%)6e−43fragment SEQ ID NO: 58644 - 20 . . . 283157/268(58%)Arabidopsis thaliana, 302 aa.[EP1033405-A2, 6 SEP 2000]AAG46600Arabidopsis thaliana protein 3 . . . 259106/268(39%)6e−43fragment SEQ ID NO: 58643 - 34 . . . 297157/268(58%)Arabidopsis thaliana, 316 aa.[EP1033405-A2, 6 SEP 2000]AAG46599Arabidopsis thaliana protein 3 . . . 259106/268(39%)fragment SEQ ID NO: 58642 - 45 . . . 308157/268(58%)Arabidopsis thaliana, 327 aa.[EP1033405-A2, 6 SEP 2000]


[0851] In a BLAST search of public sequence databases, the NOV100a protein was found to have homology to the proteins shown in the BLASTP data in Table 100D.
527TABLE 100DPublic BLASTP Results for NOV100aNOV100aIdentities/ProteinResidues/SimilaritiesAccessionMatchfor theExpectNumberProtein/Organism/LengthResiduesMatched PortionValueQ9JJN7CARBONYL REDUCTASE (EC1 . . . 279246/279 (88%)e−1401.1.1.184) (CARBONYL1 . . . 277262/279 (93%)REDUCTASE 3) - Cricetulusgriseus (Chinese hamster), 277 aa.AAH02812CARBONYL REDUCTASE 3 -1 . . . 279227/279 (81%)e−126Homo sapiens (Human), 277 aa.1 . . . 277246/279 (87%)O75828Carbonyl reductase [NADPH] 33 . . . 279226/277 (81%)e−126(EC 1.1.1.184) (NADPH-2 . . . 276245/277 (87%)dependent carbonyl reductase 3) -Homo sapiens (Human), 276 aa.Q924V2CARBONYL REDUCTASE 2 -1 . . . 279206/279 (73%)e−119Cricetulus griseus (Chinese1 . . . 277244/279 (86%)hamster), 277 aa.Q91X28SIMILAR TO CARBONYL1 . . . 279204/279 (73%)e−116REDUCTASE 1 - Mus musculus1 . . . 277240/279 (85%)(Mouse), 277 aa.


[0852] PFam analysis predicts that the NOV100a protein contains the domains shown in the Table 100E.
528TABLE 100EDomain Analysis of NOV100aIdentities/SimilaritiesNOV100a Matchfor theExpectPfam DomainRegionMatched RegionValueadh_short:4 . . . 27777/316(24%)5.2e−31domain 1 of 1186/316(59%)



Example 101

[0853] The NOV101 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 101A.
529TABLE 101ANOV101 Sequence AnalysisSEQ ID NO:2871011 bpNOV101a,CTCCTCGGGGGGGCGGCGGCGGCGATGTTCTCGGTCCTCTCGTACGGGCGGCTGGTGGCG59644-01 DNA SequenceCCCGCGCCGTGCTCGGCGGCCTCTCGCAGACCGACCCCAGGGCCGGCGGCGGCGGCGGCGGCGCCGTGCTCGGCGGCCTCTCGCAGACCGACCCCAGGGCCGGCGGCGGCGGCGGCGGCGACTACGGACTGGTGACGGCCGGCTGCGGCTTCGGGAAGGACTTCCGTAAGGGCCTCCTCAAGAAGGGCGCGTGCTACGGGGACGACGCGTGCTTCGTGGCCCGGCACCGTTCCGCGGACGTGCTCGGTGTTGCAGATGGTGTAGGAGGCTGGAGAGACTATGGAGTTGATCCATCTCAATTCTCAGGGACTTTAATGCGGACGTGTGAACGTTTAGTAAAAGAAGGACGGTTCGTACCTAGTAATCCCATTGGAATTCTCACCACAAGCTACTGTGAGTTGCTGCAAAATAAAGTCCCTTTGCTCGGTAGCAGCACCGCCTGCATTGTGGTGCTGGACAGAACCAGCCACCGCTTACACACAGCAAACCTGGGCGATTCAGGCTTCCTGGTTGTCAGGGGTGGTGAAGTCGTGCACCGATCAGATGAGCAGCAGCATTACTTCAACACTCCATTCCAGCTCTCAATCGCTCCCCCTGAAGCCGAGGGAGTCGTCTTGAGCGACAGTCCGGATGCTGCTGATAGCACGTCTTTCGATGTCCAGCTAGGAGACATTATCCTGACGGCAACAGATGGACTCTTTGACAACATGCCTGATTATATGATTCTTCAGGAGCTAAAAAAGTTAAAGAATTCAAATTATGAGAGTATACAACAGACTGCCAGAAGCATTGCTGAGCAAGCTCATGAGCTGGCCTATGACCCAAATTATATGTCACCTTTTGCACAGTTTGCATGTGACAATGGATTGAATGTGAGAGGTGGTGGAAAGCCAGATGACATCACCGTCCTTCTTTCAATAGTGGCTGAGTATACAGACTAGCTGAGGTGTCAAORF Start: ATG at 25ORF Stop: TAG at 997SEQ ID NO:288324 aaMW at 34311.1 kDNOV101a,MFSVLSYGRLVARAVLGGLSQTDPRAGGGGGGAVLGGLSQTDPRAGGGGGGDYGLVTACG59644-01 Protein SequenceGCGFGKDFRKGLLKKGACYGDDACFVARHRSADVLGVADGVGGWRDYGVDPSQFSGTLMRTCERLVKEGRFVPSNPIGILTTSYCELLQNKVPLLGSSTACIVVLDRTSHRLHTANLGDSGFLVVRGGEVVHRSDEQQHYFNTPFQLSIAPPEAEGVVLSDSPDAADSTSFDVQLGDIILTATDGLFDNMPDYMILQELKKLKNSNYESIQQTARSIAEQAHELAYDPNYMSPFAQFACDNGLNVRGGGKPDDITVLLSIVAEYTD


[0854] Further analysis of the NOV101a protein yielded the following properties shown in Table 101B.
530TABLE 101BProtein Sequence Properties NOV101aPSort0.5708 probability located in mitochondrial matrix space;analysis:0.4996 probability located in mitochondrial intermembranespace; 0.2852 probability located in mitochondrial innermembrane; 0.2852 probability located in mitochondrialouter membraneSignalPLikely cleavage site between residues 23 and 24analysis:


[0855] A search of the NOV101a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 101C.
531TABLE 101CGeneseq Results for NOV101aNOV101aIdentities/Residues/SimilaritiesGeneseqProtein/Organism/LengthMatchfor theExpectIdentifier[Patent #, Date]ResiduesMatched RegionValueAAB85357Human phosphatase (PP) (clone ID 1 . . . 324304/324 (93%) e−1733402521CD1) - Homo sapiens, 304 1 . . . 304304/324 (93%)aa. [WO200153469-A2, 26 JUL2001]AAU32112Novel human secreted protein 25 . . . 324272/300 (90%) e−156#2603 - Homo sapiens, 304 aa. 6 . . . 304274/300 (90%)[WO200179449-A2, 25 OCT2001]AAG52267Arabidopsis thaliana protein 71 . . . 320101/261 (38%)4e−33fragment SEQ ID NO: 66421 - 99 . . . 340133/261 (50%)Arabidopsis thaliana, 348 aa.[EP1033405-A2, 6 SEP 2000]AAG52266Arabidopsis thaliana protein 71 . . . 320101/261 (38%)4e−33fragment SEQ ID NO: 66420 -125 . . . 366133/261 (50%)Arabidopsis thaliana, 374 aa.[EP1033405-A2, 6 SEP 2000]AAG52265Arabidopsis thaliana protein 71 . . . 320101/261 (38%)4e−33fragment SEQ ID NO: 66419 -218 . . . 459133/261 (50%)Arabidopsis thaliana, 467 aa.[EP1033405-A2, 6 SEP 2000]


[0856] In a BLAST search of public sequence databases, the NOV101a protein was found to have homology to the proteins shown in the BLASTP data in Table 101D.
532TABLE 101DPublic BLASTP Results for NOV101aNOV101aIdentities/ProteinResidues/SimilaritiesAccessionMatchfor theExpectNumberProtein/Organism/LengthResiduesMatched PortionValueQ9W0E2CG12091 PROTETN - Drosophila 1 . . . 320163/322 (50%)1e−83melanogaster (Fruit fly), 321 aa. 1 . . . 320218/322 (67%)Q9W3R1CG15035 PROTEIN - Drosophila 55 . . . 319127/266 (47%)1e−64melanogaster (Fruit fly), 374 aa.109 . . . 373178/266 (66%)O18183W09D10.4 PROTEIN - 4 . . . 320136/331 (41%)2e−60Caenorhabditis elegans, 330 aa. 7 . . . 330198/331 (59%)Q9VAH4CG7615 PROTEIN - Drosophila 35 . . . 319122/285 (42%)2e−56melanogaster (Fruit fly), 314 aa. 26 . . . 309168/285 (58%)Q9SUK9HYPOTHETICAL 36.2 KDA 71 . . . 320101/261 (38%)1e−32PROTEIN - Arabidopsis thaliana 86 . . . 327133/261 (50%)(Mouse-ear cress), 335 aa.


[0857] PFam analysis predicts that the NOV101a protein contains the domains shown in the Table 110E.
533TABLE 101EDomain Analysis of NOV101aIdentities/SimilaritiesNOV101a Matchfor theExpectPfam DomainRegionMatched RegionValuePP2C: domain 1 of 1147 . . . 19113/48 (27%)0.2636/48 (75%)



Example 102

[0858] The NOV1102 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 102A.
534TABLE 102ANOV 102 Sequence AnalysisSEQ ID NO:289523 bpNOV102a,AGTCCCAGTACTATCAGCCATGGTCAACCACACCATGTTCTTCGACGTTGCTGTCGACCG59662-01 DNA SequenceAGTGAGCCCTTGGACCACGTCTCCTTTGAGCTGTTTGCAGAAAAGTTTCCAAAGACAGCAGAAAACGTTCGTGCTCTGAGCACTGAAGAGAAAGGATTTGGTTATAAGGGTCCCTGCTTTCACAGAATTATACCAGCATTTATGTGTCAGGGTGGTGACTTCACGCACCATAATGGCACTGGTGGCAAGTCCATCTACGGGGAGAAATTTGAAGATGAGAAATTTATCCTAAAGCGTACAGGTCCTGGCATCTTGTCCATGGCAAATTCTGGACCCAACACAAACTGTTCCGTTTTTTTCATCTGCACTGCCAAGACGGGGTGGTTGGATGGCAAGCATGTAGTCTTTGGCAAGGTGAAAGAAGGCATGAATATTTTGGAGGCCATAGAGCAATTTGGGTCCAGGAATGGCAAGACCAGCAAGAAGACCACCATTGCTGACTGTGGACAGCTCTGGTAAGTTTGAORF Start: ATG at 20ORF Stop: TAA at 515SEQ ID NO:290165 aaMW at 18237.7 kDNOV102a,MVNHTMFFDVAVDSEPLDHVSFELFAEKFPKTAENVRALSTEEKGFGYKGPCFHRIIPCG59662-01 DNA SequenceAFMCQGGDFTHHNGTGGKSIYGEKFEDEKFILKRTGPGILSMANSGPNTNCSVFFICTAKTGWLDGKHVVFGKVKEGMNILEAIEQFGSRNGKTSKKTTIADCGQLW


[0859] Further analysis of the NOV102a protein yielded the following properties shown in Table 102B.
535TABLE 102BProtein Sequence Properties NOV102aPSort0.6400 probability located in microbody (peroxisome);analysis:0.4500 probability located in cytoplasm; 0.1000probability located in mitochondrial matrix space;0.1000 probability located in lysosome (lumen)SignalPNo Known Signal Sequence Predictedanalysis:


[0860] A search of the NOV102a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 102C.
536TABLE 102CGeneseq Results for NOV102aNOV102aIdentities/Residues/SimilaritiesGeneseqProtein/Organism/LengthMatchfor theExpectIdentifier[Patent #, Date]ResiduesMatched RegionValueAAU01195Human cyclophilin A protein -1 . . . 164141/164 (85%)1e−80Homo sapiens, 165 aa.1 . . . 164148/164 (89%)[WO200132876-A2, 10 MAY2001]AAW56028Calcineurin protein - Mammalia,1 . . . 164141/164 (85%)1e−80165 aa. [WO9808956-A2,1 . . . 164148/164 (89%)5 MAR 1998]AAG65275Haematopoietic stem cell2 . . . 164140/163 (85%)5e−80proliferation agent related human1 . . . 163147/163 (89%)protein #2 - Homo sapiens, 164 aa.[JP2001163798-A, 19 JUN 2001]AAP90431Cyclophulin - Homo sapiens2 . . . 164140/163 (85%)5e−80(human), 164 aa. [EP326067-A,1 . . . 163147/163 (89%)2 AUG 1989]AAG03831Human secreted protein, SEQ ID1 . . . 164140/164 (85%)8e−80NO: 7912 - Homo sapiens, 165 aa.1 . . . 164147/164 (89%)[EP1033401-A2, 6 SEP 2000]


[0861] In a BLAST search of public sequence databases, the NOV102a protein was found to have homology to the proteins shown in the BLASTP data in Table 102D.
537TABLE 102DPublic BLASTP Results for NOV102aNOV102aIdentities/ProteinResidues/SimilaritiesAccessionMatchfor theExpectNumberProtein/Organism/LengthResiduesMatched PortionValueCAC39529SEQUENCE 26 FROM PATENT1 . . . 164141/164 (85%)4e−80(Human), 165 aa.1 . . . 164148/164 (89%)Q9BRU4PEPTIDYLPROLYL ISOMERASE1 . . . 164140/164 (85%)2e−79A (CYCLOPHILIN A) - Homo1 . . . 164147/164 (89%)sapiens (Human), 165 aa.P05092Peptidyl-prolyl cis-trans isomerase2 . . . 164140/163 (85%)2e−79A (EC 5.2.1.8) (PPIase) (Rotamase)1 . . . 163147/163 (89%)(Cyclophilin A) (Cyclosporin A-binding protein) - Homo sapiens(Human),, 164 aa.Q961X3PEPTIDYLPROLYL ISOMERASE1 . . . 164140/164 (85%)5e−79A (CYCLOPHILIN A) - Homo1 . . . 164147/164 (89%)sapiens (Human), 165 aa.P04374Peptidyl-prolyl cis-trans isomerase2 . . . 164138/163 (84%)7e−79A (EC 5.2.1.8) (PPIase) (Rotamase)1 . . . 163147/163 (89%)(Cyclophilin A) (Cyclosporin A-binding protein) - Bos taurus(Bovine), and, 163 aa.


[0862] PFam analysis predicts that the NOV102a protein contains the domains shown in the Table 102E.
538TABLE 102EDomain Analysis of NOV102aIdentities/SimilaritiesNOV102a Matchfor theExpectPfam DomainRegionMatched RegionValuepro_isomerase:5 . . . 165105/180 (58%)4.2e−91domain 1 of 1141/180 (78%)



Example 103

[0863] The NOV103 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 103A.
539TABLE 103ANOV103 Sequence AnalysisSEQ ID NO:2918860 bpNOV103a,GGATCCTTGAGGGCACTGGTGCGACTTTCAGGTGAGGTCTTAGCAGATGAAAGCGGCTCG59773-01 DNA SequenceGGCTGTGGCCCGCGCCAGTAGTGCTTTCTGCTCCGCACTCGCCGTGAGCCAGGTGTGCAACCGGATTTGGGGCGAGGGTCGCGCTGGCTACCTCGCATGCGCAGAGCCGGAAGCCCGCTGACCGGACTACAGCTCCCAGAAGAGCCTTGTGGAGGCCGCAGACGCGAAGCCGCTGGCGCCATCTTGAAATCTGATCCTCCATCCCCGAGGCTTTGCGTCTGCGCGGCCGGCCGCTGCTGCTCCGGGAGCCCAGTCTGCTAAAAGGGGAGGACGTTGAGGACGCGGCGGCTGGCGGGAGAGACAGCTGGGGAGAGACATGGCAGGGTCGGAGCGCGGCCTGCGCCTCTGTCACTCAGCATCCTCTTAGGCGTTTCCACGCCCGCCCCCTGCCCGAGGGGCGGGGCTGACGGCTCTGGTACCCGGAGTCGGCGCGCGGGGCAGGGGCGCGCCCCTGCAGAGTGGGGACCCCACTGGGCTGTGCCATGCTGACCGGAGACCACCGAGGCGGGAGACAGAGCGCGGCGAAGAGCCATTGAGTGGTCACCCAGTAGCCGCCGCCGCCGCCGCCTCGGGAAGCTTGCCACCCGCTAGGAGGGAAGATGAAGGAGATTTGCAGGATCTGTGCCCGAGAGCTGTGTGGAAACCAGCGGCGCTGGATCTTCCACACGGCGTCCAAGCTCAATCTCCAGGTTCTGCTTTCGCACGTCTTGGGCAAGGATGTCCCCCGCGATGGCAAAGCCGAGTTCGCTTGCAGCAAGTGTGCTTTCATGCTTGATCGAATCTATCGATTCGACACAGTTATTGCCCGGATTGAAGCGCTTTCTATTGAGCGCTTGCAAAAGCTGCTACTGGAGAAGGATCGCCTCAAGTTCTGCATTGCCAGTATGTATCGGAAGAATAACGATGACTCTGGCGCGGAGATCAAGGCGGGGAATGGGACGGTTGACATGTCCGTCTTACCCGATGCGAGATACTCTGCACTGCTCCAGGAGGACTTCGCCTATTCAGGGTTTGAGTGCTGGGTGGAGAATGAGGATCAGATCCAGGAGCCACACAGCTGCCATGGTTCAGAAGGCCCTGGAAACCGACCCAGGAGATGCCGTGGTTGTGCCGCTTTGCGGGTTGCTGATTCTGACTATGAAGCCATTTGTAAGGTACCTCGAAAGGTGGCCAGAAGTATCTCCTGCGGCCCTTCTAGCAGGTGGTCGACCAGCATTTGCACTGAAGAACCAGCGTTGTCTGAGGTTGGGCCACCCGACTTAGCAAGCACAAAGGTACCCCCAGATGGAGAAAGCATGGAGGAAGAGACGCCTGGTTCCTCTGTGGAATCTTTGGATGCAAGCGTCCAGGCTAGCCCTCCACAACAGAAAGATGAGGAGACTGAGAGAAGTGCAAAGGAACTTGGAAAGTGTGACTGTTGTTCAGATGATCAGGCTCCGCAGCATGGGTGTAATCACAAGCTGGAATTAGCTCTTAGCATGATTAAAGGTCTTGATTATAAGCCCATCCAGAGCCCCCGAGGGAGCAGGCTTCCGATTCCAGTGAAATCCAGCCTACCTGGAGCCAAGCCTGGCCCTAGCATGACAGATGGAGTTAGTTCCGGTTTCCTTAACAGGTCTTTGAAACCCCTTTACAAGACACCTGTGAGTTATCCCTTGGAGCTTTCAGACCTGCAGGAGCTGTGGGATGATCTCTGTGAAGATTATTTGCCGCTCCGGGTCCAGCCCATGACTGAAGAGTTGCTGAAACAACAAAAGCTGAATTCACATGAGACCACTATAACTCAGCAGTCTGTATCTGATTCCCACTTGGCAGAACTCCAGGAAAAAATCCAGCAAACAGAGGCCACCAACAAGATTCTTCAAGAGAAACTTAATGAAATGAGCTATGAACTAAAGTGTGCTCAGGAGTCGTCTCAAAAGCAAGATGGTACAATTCAGAACCTCAAGGAAACTCTGAAAAGCAGGGAACGTGAGACTGAGGAGTTGTACCAGGTAATTGAAGGTCAAAATGACACAATGGCAAAGCTTCGAGAAATGCTGCACCAAAGCCAGCTTGGACAACTTCACAGCTCAGAGGGTACTTCTCCAGCTCAGCAACAGGTAGCTCTGCTTGATCTTCAGAGTGCTTTATTCTGCAGCCAACTTGAAATACAGAAGCTCCAGAGGGTGGTACGACAGAAAGAGCGCCAACTGGCTGATGCCAAACAATGTGTGCAATTTGTAGAGGCTGCAGCACACGAGAGTGAACAGCAGAAAGAGGCTTCTTGGAAACATAACCAGGAATTGCGAAAAGCCTTGCAGCAGCTACAAGAAGAATTGCAGAATAAGAGCCAACAGCTTCGTGCCTGGGAGGCTGAAAAATACAATGAGATTCGAACCCAGGAACAAAACATCCAGCACCTAAACCATAGTCTGAGTCACAAGGAGCAGTTGCTTCAGGAATTTCGGGAGCTCCTACAGTATCGAGATAACTCAGACAAAACCCTTGAAGCAAATGAAATGTTGCTTGAGAAACTTCGCCAGCGAATACATGATAAAGCTGTTGCTCTGGAGCGGGCTATAGATGAAAAATTCTCTGCTCTAGAAGAGAAAGAAAAAGAACTGCGCCAGCTTCGTCTTGCTGTGAGAGAGCGAGATCATGACTTAGAGAGACTGCGCGATGTCCTCTCCTCCAATGAAGCTACTATGCAAAGTATGGAGAGTCTCCTGAGGGCCAAAGGCCTGGAAGTGGAACAGTTATCTACTACCTGTCAAAACCTCCAGTGGCTGAAAGAAGAAATGGAAACCAAATTTAGCCGTTGGCAGAAGGAACAAGAGAGTATCATTCAGCAGTTACAGACGTCTCTTCATGATAGGAACAAAGAAGTGGAGGATCTTAGTGCAACACTGCTCTGCAAACTTGGACCAGGGCAGAGTGAGATAGCAGAGGAGCTGTGCCAGCGTCTACAGCGAAAGGAAAGGATGCTGCAGGACCTTCTAAGTGATCGAAATAAACAAGTGCTGGAACATGAAATGGAGATTCAAGGCCTGCTTCAGTCTGTGAGCACCAGGGAGCAGGAAAGCCAAGCTGCTGCAGAGAAGTTGGTGCAAGCCTTAATGGAAAGAAATTCAGAATTACAGGCCCTGCGCCAATATTTAGGAGGGAGAGACTCCCTGATGTCCCAAGCACCCATCTCTAACCAACAAGCTGAAGTTACCCCCACTGGCCGTCTTGGAAAACAGACTGATCAAGGTTCAATGCAGATACCTTCCAGAGATGATAGCACTTCATTGACTGCCAAAGAGGATGTCAGCATACCCAGATCCACATTAGGAGACTTGGACACAGTTGCAGGGCTGGAAAAAGAACTGAGTAATGCCAAAGAGGAACTTGAACTCATGGCTAAAAAAGAAAGAGAAAGTCAGATGGAACTTTCTGCTCTACAGTCCATGATGGCTGTGCAGGAAGAAGAGCTGCAGGTGCAGGCTGCTGATATGGAGTCTCTGACCAGGAACATACAGATTAAAGAAGATCTCATAAAGGACCTGCAAATGCAACTGGTTGATCCTGAAGACATACCAGCTATGGAACGCCTGACCCAGGAAGTCTTACTTCTTCGGGAAAAAGTTGCTTCAGTAGAATCCCAGGGTCAAGAAATTTCAGGAAACCGAAGACAACAGTTGCTGCTGATGCTAGAAGGACTAGTAGATGAACGGAGTCGGCTCAATGAGGCCTTACAAGCAGAGAGACAGCTCTATAGCAGTCTGGTGAAGTTCCATGCCCATCCAGAGAGCTCTGAGAGAGACCGAACTCTGCAGGTGGAACTGGAAGGGGCTCAGGTGTTACGCAGTCGGCTAGAAGAAGTTCTTGGAAGAAGCTTGGAGCGCTTAAACAGGCTGGAGACCCTGGCCGCCATTGGAGGTGCAGCTGCAGGGGATGACACCGAAGATACAAGCACTGAGTTCACTGACAGTATTGAGGAGGAGGCTGCACACCATAGTCACCAGCAACTTGTCAAGGTGGCTTTGGAGAAAAGTCTGGCAACTGTGGAGACCCAGAACCCATCTTTTTCCCCTCCTTCTCCGATGGGAGGGGACAGTAACAGGTGTCTTCAGGAAGAAATGCTCCACCTGAGGGCTGAGTTCCACCAGCACTTAGAAGAGAAGAGGAAAGCTGAGGAGGAACTGAAGGAGCTAAAGGCTCAAATTGAGGAAGCAGGATTCTCCTCAGTGTCCCACATCAGGAACACCATGCTGAGCCTTTGCCTTGAGAATGCGGAGCTGAAAGAGCAGATGGGAGAAGCAATGTCTGATGGATGGGAGATCGAGGAAGACAAGGAGAAGGGCGAGGTGATGGTTGAGACTGTGGTAACCAAAGAGGGTCTGAGTGAGAGTAGCCTTCAGGCTGAGTTCAGAAAGCTCCAGGGAAAACTGAAGAATGCCCACAATATCATCAACCTCCTCAAAGAACAACTTGTGCTGAGTAGCAAGGAAGGGAATAGTAAACTTACTCCAGAGCTCCTTGTGCATCTGACCAGCACCATTGAAAGAATAAACACAGAACTGGTTGGTTCCCCTGGGAAGCACCAACACCAAGAGGAGGGGAATGTGACTGTGAGGCCTTTCCCCAGACCCCAGAGCCTTGACCTTGGGGCTACCTTCACAGTGGATGCCCACCAATTGGATAACCAGTCCCAGCCTCGTGACCCTGGGCCTCAGTCAGCGTTTAGCCTACCAGGGTCCACCCAGCACCTGCGCTCCCAGCTGTCACAATGCAAACAACGCTATCAAGATCTCCAGGAGAAGCTGCTGCTATCAGAAGCCACTGTCTTTGCTCAGGCTAACGAGCTGGAGAAATACAGAGTTATGCTTACAGGTGAATCCTTGGTGAAGCAGGACAGCCAGCAGATCCAGGTGGACCTCCAGGACCTGGGCTATGAGACTTGTGGCCGAAGCGAGAATGAGGCTGAACGGGAGGAAACCACCAGTCCTGAGTGTGAGGAGCACAACAGCCTCAAGGAAATGGTCCTGATGGAGGGGCTGTGCTCTGAGCAGGGACGCCGGGGCTCAACACTGGCTAGTTCCTCTGAGAGGAAGCCCTTGGAGAACCAGCTAGGGAAGCAGGAAGAGTTCCGGGTATATGGAAAGTCAGAAAACATCTTGGTCCTACGAAAGGACATCAAAGATCTGAAGGCCCAGCTGCAGAATGCCAACAAGGTCATTCAAAACCTCAAGAGCCGGGTCCGGTCCCTCTCAGTTACAAGTGATTATTCGTCTAGTCTGGAAAGACCCCGGAAGCTGAGAGCTGTTGGCACCTTGGAGGGGTCTTCACCTCATAGTGTCCCTGATGAGGATGAGGGGTGGCTGTCTGATGGCACTGGGGCTTTCTACTCTCCAGGGCTTCAGGCCAAAAAGGACCTGGAGAGTCTCATCCAGAGAGTATCCCAGCTGGAGGCCCAGCTCCCAAAAAATGGACTAGAAGAGAAGCTGGCTGAGGAGCTGAGATCAGCCTCGTGGCCTGGGAAATATGATTCCCTGATTCAGGATCAGGCCCGGGAACTGTCTTACCTACGGCAAAAAATACGAGTGAGGATCTCCTAAGGAGCAATGACATTGACTACTACCTGGGACAGAGCTTCCGGGAGTGAGGATCTCCTAAGGAGCAATGACATTGACTACTACCTGGGACAGAGCTTCCGGGAGCAACTCGCCCAGGGAAGCCAGCTGACAGAGAGGCTCACCAGCAAACTCAGCACCAAGGATCATAAAAGTGAGAAAGATCAAGCTGGACTTGAGCCACTGGCCCTCAGGCTCAGCAGGGAGCTGCAGGAGAAGGAGAAAGTGATTGAAGTCCTGCAGGCCAAGCTGGATGCTCGGTCCCTCACACCCTCCAGCAGCCATGCCTTGTCTGACTCCCACCGCTCTCCCAGCAGCACCTCTTTCCTGTCTGATGAACTGGAAGCCTGCTCTGACATGGACATAGTCAGCGAGTACACACACTATGAAGAGAAGAAAGCTTCTCCCAGTCACTCAGATTCCATCCATCATTCGAGTCATTCTGCTGTGTTGTCTTCTAAACCATCATCAACCAGTGCATCTCAGGGGGCTAAGGCCGAATCCAACAGCAACCCCATCAGCTTGCCAACTCCCCAGAATACCCCCAAGGAGGCCAACCAGGCCCATTCAGGCTTTCATTTTCACTCCATACCCAAGCTGGCTAGCCTTCCTCAGGCACCATTGCCCTCAGCTCCATCCAGCTTCCTGCCTTTCAGCCCCACTGGCCCTCTCCTCCTTGGCTGCTGTGAGACACCAGTGGTCTCCTTGGCTGAGGCTCAGCAGGAGCTACAGATGCTGCAGAAGCAGTTGGGAGAAAGTGCCAGCACTGTTCCTCCTGCTTCCACAGCTACATTGCTGAGCAACGACTTGGAAGCCGACTCTTCCTACTACCTCAACTCTGCCCAGCCTCACTCTCCTCCAAGGGGCACCATAGAACTGGGAAGAATCCTAGAGCCTGGGTACCTGGGCAGCAGTGGCAAGTGGGATGTGATGAGGCCTCAGAAAGGGAGTGTATCTGGGGACCTATCCTCAGGCTCCTCTGTGTACCAGCTTAACTCCAAACCCACAGGGGCTGACCTGCTGGAAGAGCATCTTGGTGAAATCCGGAACCTGCGCCAGCGCCTGGAGGAGTCCATCTGCATCAATGACCGCCTACGGGAGCAACTGGAACACCGGCTGACCTCTACTGCTCGTGGAAGGGGATCCACTTCTAACTTCTACAGTCAGGGCCTGGAGTCCATACCTCAGCTCTGCAATGAGAACAGAGTCCTCAGGGAAGACAATCGAAGACTTCAGGCTCAACTGAGTCATGTTTCCAGAGAGCACTCCCAGGAAACAGAAAGCCTGAGGGAGGCTCTGCTGTCCTCTCGATCCCACCTTCAAGAGCTGGAAAAGGAGCTGGAGCACCAGAAGGTGGAAAGGCAGCAGCTTTTGGAAGACTTGAGGGAGAAGCAGCAAGAGGTCTTGCATTTCAGGGAGGAACGTCTTTCCCTCCAGGAAAACGACTCCAGACTGCAGCACAAGCTGGTTCTCCTGCAGCAACAGTGTGAAGAGAAACAGCAGCTCTTTGAGTCCCTCCAGTCAGAGCTACAAATCTACGAGGCACTTTATGGCAATTCCAAGAAGGGGCTGAAAGGCTTGGGTTTGGATACTTCTCCAGTAATGAAGACCCCTCCCAAGCTAGAGGGTGATGCTACTGATGGCTCCTTTGCCAATAAGCATGGCCGCCATGTCATTGGCCACATTGATGACTACAGTGCCCTAAGACAGCAGATTGCGGAGGGCAAGCTGCTGGTCAAAAAGATAGTGTCTCTTGTGAGATCAGCGTGCAGCTTCCCTGGCCTTGAAGCCCAAGGCACAGAGGTGCTAGGCAGCAAAGGTATTCATGAGCTTCGGAGCAGCACCAGTGCCCTGCACCATGCCCTAGAGGAGTCGGCTTCCCTCCTCACCATGTTCTGGAGAGCAGCCCTGCCAAGCACCCACATCCCTGTGCTGCCTGGCAAAGTGGGAGAATCAACAGAAAGGGAACTTCTGGAACTGAGAACCAAAGTATCCAAACAGGAGCGGCTCCTTCAGAGCACAACTGAGCATCTGAAGAACGCCAACCAGCAGAAGGAGAGCATGGAGCAGTTCATCGTCAGCCAGCTAACCAGAACACATGATGTTTTAAAGAAGGCAAGGACTAACTTAGAGGTGAAATCCCTAAGGGCTCTGCCATGTACTCCAGCCTTGTGACCCTTGCCTTCCAGGAACCATGCAAGAAGCGCAGCCACCAGAAGTCCTTAAAACAGCAGGAAAGGTGGGCCTGTCCCCCTTTTGTGCAGCTACCTATCTGCTGAGGAGCATCTGGGCCTCATTCCTCCAAGTCCACGGGAGGGTCCAGAAGAGGGAGTCAGAGATGTATCCTGGTGGAGCTGGGAGAAAGGCAGAAAGCCTTTCTGACAGCTATGGAATACGATTAGCCAAGGTCCACTTGGCCCAGCACTAAGAAAAAGATGCGTAGTTTGCACAGAAGGTTTTGTGATCCTGCCTCTCAACAGCCCCAGCAGCTTGGGAACTAGCAAGAGCACATTTCTTGCCTCATCAGCTGTCCTGAGATGGAAAACTCAGTGGATATAGGACCCTGATTCCGATGAAAGGGGCACGTGGTCCCAATGCTGGAGCTCCTCTGGCAGGTTCTAAAAGCACACTACTGAGCAGCGGTGCCCTGCCGGACACTGCTGGCGGGGGCTCAGTGAGCACTACTCACAGATCCACACCTGACCCTGTTGGGTCGAGTCAGGCTGGGCCTTGGTCTGCACTGTAGCACCTGTGTTCTTTGAGTTCACATCATGAATGTGGTGACTTCCCAGATACCATCTCAGGCTTAACCTAGCACATCCTATTTCTTTTCTTCTATGATATCCAAATTGGACTGACCTCACTTCAAAGTTGCTGTCCCATTTTGTCACCCTATCTTATCTCGGGGAAATTGCAGACTGATGGCCAGACCAACTCTGTTGAAATTCTTGCATAGAGCAAACCTGTGCTCATTTTTAAGTGGCATGGGAGAGGCCCCCAGCCTAGTAAAGCCTAGTCTGTGTCTTCACAGTGCTGGTAGAATGTGTTTGTGTGTATAAATATATGATATAGATTTATATATGTTGCTAACGCCATATATTGAAGGCCAACATAACTGGTGGACAGGGTGGGTGACAGAAAATGAAAGCCTTTTTGGTGATTGTTAAAGCAAGATGTGTATAAAGAAATAAATAGTTTTTCTTTCORF Start: ATG at 658ORF Stop: TGA at 7828SEQ ID NO:2922390 aaMW at 268843.7 kDNOV103a,MKEICRICARELCGNQRRWIFHTASKLNLQVLLSHVLGKDVPRDGKAEFACSKCAFMLCG59773-01 ProteinSequenceDRIYRFDTVIARIEALSIERLQKLLLEKDRLKFCIASMYRKNNDDSGAEIKAGNGTVDMSVLPDARYSALLQEDFAYSGFECWVENEDQIQEPHSCHGSEGPGNRPRRCRGCAALRVADSDYEAICKVPRKVARSISCGPSSRWSTSICTEEPALSEVGPPDLASTKVPPDGESMEEETPGSSVESLDASVQASPPQQKDEETERSAKELGKCDCCSDDQAPQHGCNHKLELALSMIKGLDYKPIQSPRGSRLPIPVKSSLPGAKPGPSMTDGVSSGFLNRSLKPLYKTPVSYPLELSDLQELWDDLCEDYLPLRVQPMTEELLKQQKLNSHETTITQQSVSDSHLAELQEKIQQTEATNKILQEKLNEMSYELKCAQESSQKQDGTIQNLKETLKSRERETEELYQVIEGQNDTMAKLREMLHQSQLGQLHSSEGTSPAQQQVALLDLQSALFCSQLEIQKLQRVVRQKERQLADAKQCVQFVEAAAHESEQQKEASWKHNQELRKALQQLQEELQNKSQQLRAWEAEKYNEIRTQEQNIQHLNHSLSHKEQLLQEFRELLQYRDNSDKTLEANEMLLEKLRQRIHDKAVALERAIDEKFSALEEKEKELRQLRLAVRERDHDLERLRDVLSSNEATMQSMESLLRAKGLEVEQLSTTCQNLQWLKEEMETKFSRWQKEQESIIQQLQTSLHDRNKEVEDLSATLLCKLGPGQSEIAEELCQRLQRKERMLQDLLSDRNKQVLEHEMEIQGLLQSVSTREQESQAAAEKLVQALMERNSELQALRQYLGGRDSLMSQAPISNQQAEVTPTGRLGKQTDQGSMQIPSRDDSTSLTAKEDVSIPRSTLGDLDTVAGLEKELSNAKEELELMAKKERESQMELSALQSMMAVQEEELQVQAADMESLTRNIQIKEDLIKDLQMQLVDPEDIPAMERLTQEVLLLREKVASVESQGQEISGNRRQQLLLMLEGLVDERSRLNEALQAERQLYSSLVKFHAHPESSERDRTLQVELEGAQVLRSRLEEVLGRSLERLNRLETLAAIGGAAAGDDTEDTSTEFTDSIEEEAAHHSHQQLVKVALEKSLATVETQNPSFSPPSPMGGDSNRCLQEEMLHLRAEFHQHLEEKRKAEEELKELKAQIEEAGFSSVSHIRNTMLSLCLENAELKEQMGEAMSDGWEIEEDKEKGEVMVETVVTKEGLSESSLQAEFRKLQGKLKNAHNIINLLKEQLVLSSKEGNSKLTPELLVHLTSTIERINTELVGSPGKHQHQEEGNVTVRPFPRPQSLDLGATFTVDAHQLDNQSQPRDPGPQSAFSLPGSTQHLRSQLSQCKQRYQDLQEKLLLSEATVFAQANELEKYRVMLTGESLVKQDSKQIQVDLQDLGYETCGRSENEAEREETTSPECEEHNSLKEMVLMEGLCSEQGRRGSTLASSSERKPLENQLGKQEEFRVYGKSENILVLRKDIKDLKAQLQNANKVIQNLKSRVRSLSVTSDYSSSLERPRKLRAVGTLEGSSPHSVPDEDEGWLSDGTGAFYSPGLQADDKLESLIQRVSQLEAQLPKNGLEEKLAEELRSASWPGKYDSLIQDQARELSYLRQKIREGRGICYLITRHAKDTVKSFEDLLRSNDIDYYLGQSFREQLAQGSQLTERLTSKLSTKDHKSEKDQAGLEPLALRLSRELQEKEKVIEVLQAKLDARSLTPSSSHALSDSHRSPSSTSFLSDELEACSDMDIVSEYTHYEEKKASPSHSDSIHHSSHSAVLSSKPSSTSASQGAKAESNSNPISLPTPQNTPKEANQAHSGFHFHSIPKLASLPQAPLPSAPSSFLPFSPTGPLLLGCCETPVVSLAEAQQELQMLQKQLGESASTVPPASTATLLSNDLEADSSYYLNSAQPHSPPRGTIELGRILEPGYLGSSGKWDVMRPQKGSVSGDLSSGSSVYQLNSKPTGADLLEEHLGEIRNLRQRLEESICINDRLREQLEHRLTSTARGRGSTSNFYSQGLESIPQLCNENRVLREDNRRLQAQLSHVSREHSQETESLREALLSSRSHLQELEKELEHQKVERQQLLEDLREKQQEVLHFREERLSLQENDSRLQHKLVLLQQQCEEKQQLFESLQSELQIYEALYGNSKKGLKGLGLDTSPVMKTPPKLEGDATDGSFANKHGRHVIGHIDDYSALRQQIAEGKLLVKKIVSLVRSACSFPGLEAQGTEVLGSKGIHELRSSTSALHHALEESASLLTMFWRAALPSTHIPVLPGKVGESTERELLELRTKVSKQERLLQSTTEHLKNANQQKESMEQFIVSQLTRTHDVLKKARTNLEVKSLRALPCTPALSEQ ID NO:2937161 bpNOV103b,GTTGAGGGGGCAATCGGGCACGCTCCTCCCCATGGGTTGCCCATCATGTCTAATGGATCG59773-02 DNA SequenceATCGCACTCTGTCCCAGCACCTCAATGACCTGAAGAAGGAGAACTTCAGCCTCAAGCTGCGCATCTACTTCCTGGAGGAGCGCATGCAACAGAAGTATGAGGCCAGCCGGGAGGACATCTACAAGCGGAACATTGAGCTGAAGGTTGAAGTGGAGAGCTTGAAACGAGAACTCCAGGACAAGAAACAGCATCTGGATAAAACATGGGCTGATGTGGAGAATCTCAACAGTCAGAATGAAGCTGAGCTCCGACGCCAGTTTGAGGAGCGACAGCAGGAGACGGAGCATGTTTATGAGCTCTTGGAGAATAAGATCCAGCTTCTGCAGGAGGAATCCAGGCTAGCAAAGAATGAAGCTGCGCGGATGGCAGCTCTGGTGGAAGCAGAGAAGGAGTGTAACCTGGAGCTCTCAGAGAAACTGAAGGGAGTCACCAAAAACTGGGAAGATGTACCAGGAGACCAGGTCAAGCCCGACCAATACACTGAGGCCCTGGCCCAGAGGGACAGGAGAATTGAAGAACTGAATCAGAGCCTGGCTGCCCAGGAGAGGCTTGTAGAACAGCTATCTCGGGAGAAACAACAACTGCTACATCTGTTGGAGGAGCCAACTAGCATGGAAGTGCAGCCCATGACTGAAGAGTTGCTGAAACAACAAAAGCTGAATTCACATGAGACCACTATAACTCAGCAGTCTGTATCTGATTCCCACTTGGCAGAACTCCAGGAAAAAATCCAGCAAACAGAGGCCACCAACAAGATTCTTCAAGAGAAACTTAATGAAATGAGCTATGAACTAAAGTGTGCTCAGGAGTCGTCTCAAAAGCAAGATGGTACAATTCAGAACCTCAAGGAAACTCTGAAAAGCAGGGAACGTGAGACTGAGGAGTTGTACCAGGTAATTGAAGGTCAAAATGACACAATGGCAAAGCTTCGAGAAATGCTGCACCAAAGCCAGCTTGGACAACTTCAGAGCTCAGAGGGTACTTCTCCAGCTCAGCAACAGGTAGCTCTGCTTGATCTTCAGAGTGCTTTATTCTGCAGCCAACTTGAAATACAGAAGCTCCAGAGGGTGGTACGACAGAAAGAGCGCCAACTGGCTGATGCCAAACAATGTGTGCAATTTGTAGAGGCTGCAGCACACGAGAGTGAACAGCAGAAAGAGGCTTCTTGGAAACATAACCAGGAATTGCGAAAAGCCTTGCAGCAGCTACAAGAAGAATTGCAGAATAAGAGCCAACAGCTTCGTGCCTGGGAGGCTGAAAAATACAATGAGATTCGAACCCAGGAACAAAACATCCAGCACCTAAACCATAGTCTGAGTCACAAGGAGCAGTTGCTTCAGGAATTTCGGGAGCTCCTACAGTATCGAGATAACTCAGACAAAACCCTTGAAGCAAATGAAATGTTGCTTGAGAAACTTCGCCAGCGAATACATGATAAAGCTGTTGCTCTGGAGCGGGCTATAGATGAAAAATTCTCTGCTCTAGAAGAGAAAGAAAAAGAACTGCGCCAGCTTCGTCTTGCTGTGAGAGAGCGAGATCATGACTTAGAGAGACTGCGCGATGTCCTCTCCTCCAATGAAGCTACTATGCAAAGTATGGAGAGTCTCCTGAGGGCCAAAGGCCTGGAAGTGGAACAGTTATCTACTACCTGTCAAAACCTCCAGTGGCTGAAAGAAGAAATGGAAACCAAATTTAGCCGTTGGCAGAAGGAACAAGAGAGTATCATTCAGCAGTTACAGACGTCTCTTCATGATAGGAACAAAGAAGTGGAGGATCTTAGTGCAACACTGCTCTGCAAACTTGGACCAGGGCAGAGTGAGATAGCAGAGGAGCTGTGCCAGCGTCTACAGCGAAAGGAAAGGATGCTGCAGGACCTTCTAAGTGATCGAAATAAACAAGTGCTGGAACATGAAATGGAGATTCAAGGCCTGCCTCAGTCTGTGAGCACCAGGGAGCAGGAAAGCCAAGCTGCTGCAGAGAAGTTGGTGCAAGCCTTAATGGAAAGAAATTCAGAATTACAGGCCCTGCGCCAATATTTAGGAGGGAGAGACTCCCTGATGTCCCAAGCACCCATCTCTAACCAACAAGCTGAAGTTACCCCCACTGGCCGTCTTGGAAAACAGACTGATCAAGGTTCAATGCAGATACCTTCCAGAGATGATAGCACTTCATTGACTGCCAAAGAGGATGTCAGCATACCCAGATCCACATTAGGAGATTTGGACACAGTTGCAGGGCTGGAAAAAGAACTGAGTAATGCCAAAGAGGAACTTGAACTCATGGCTAAAAAAGAAAGAGAATCACAGATGGAACTTTCTGCTCTACAGTCCATGATGGCTGTGCAGGAAGAAGAGCTGCAGGTGCAGGCTGCTGATATGGAGTCTCTGACCAGGAACATACAGATTAAAGAAGATCTCATAAAGGACCTGCAAATGCAACTGGTTGATCCTGAAGACATACCAGCTATGGAACGCCTGACCCAGGAAGTCTTACTTCTTCGGGAAAAAGTTGCTTCAGTAGAATCCCAGGGTCAAGAAATTTCAGGAAACCGAAGACAACAGCAGTTGCTGCTGATGCTAGAAGGACTAGTAGATGAACGGAGTCGGCTCAATGAGGCCTTACAAGCAGAGAGACAGCTCTATAGCAGTCTGGTGAAGTTCCATGCCCATCCAGAGAGCTCTGAGAGAGACCGAACTCTGCAGGTGGAACTGGAAGGGGCTCAGGTGTTACGCAGTCGGCTAGAAGAAGTTCTTGGAAGAAGCTTGGAGCGCTTAAACAGGCTGGAGACCCTGGCCGCCATTGGAGGTGCAGCTGCAGGGGATGACACCGAAGATACAAGCACTGAGTTCACTGACAGTATTGAGGAGGAGGCTGCACACCATAGTCACCAGCAACTTGTCAAGGTGGCTTTGGAGAAAAGTCTGGCAACTGTGGAGACCCAGAACCCATCTTTTTCCCCTCCTTCTCCGATGGGAGGGGACAGTAACAGGTGTCTTCAGGAAGAAATGCTCCACCTGAGGGCTGAGATCCACCAGCACTTAGAAGAGAAGAGGAAAGCTGAGGAGGAACTGAAGGAGCTAAAGGCTCAAATTGAGGAAGCAGGATTCTCCTCAGTGTCCCACATCAGGAACACCATGCTGAGCCTTTGCCTTGAGAATGCGGAGCTGAAAGAGCAGATGGGAGAAACAATGTCTGATGGATGGGAGATCGAGGAAGACAAGGAGAAGGGCGAGGTGATGGTTGAGACTGTGGTAACCAAAGAGGGTCTGAGTGAGAGTAGCCTTCAGGCTGAGTTCAGAAAGCTCCAGGGAAAACTGAAGAATGCCCACAATATCATCAACCTCCTCAAAGAACAACTTGTGCTGAGTAGCAAGGAAGGGAATAGTAAACTTACTCCAGAGCTCCTTGTGCATCTGACCAGCACCATCGAAAGAATAAACACAGAACTGGTTGGTTCCCCTGGGAAGCACCAACACCAAGAGGAGGGGAATGTGACTGTGAGGCCTTTCCCCAGACCCCAGAGCCTTGACCTTGGGGCTACCTTCACAGTGGATGCCCACCAACAGTTGGATAACCAGTCCCAGCCTCGTGACCCTGGGCCTCAGCCAGCGTTTAGCCTACCAGGGTCCACCCAGCACCTGCGCTCCCAGCTGTCACAATGCAAACAACGCTATCAAGATCTCCAGGAGAAGCTGCTGCTATCAGAAGCCACTGTCTTTGCTCAGGCTAACGAGCTGGAGAAATACAGAGTTATGCTTAGTGAATCCTTGGTGAAGCAGGACAGCAAGCAGATCCAGGTGGACTTCCAGGACCTGGGCTATGAGACTTGTGGCCGAAGCGAGAATGAGGCTGAACGGGAGGAAACCACCAGTCCTGAGTGTGAGGAGCACAACAGCCTCAAGGAAATGGTCCTGATGGAGGGGCTGTGCTCTGAGCAGGGACGCCGGGGCTCAACACTGGCTAGTTCCTCTGAGAGGAAGCCCTTGGAGAACCAGCTAGGGAAGCAGGAAGAGTTCCGGGTATATGGAAAGTCAGAAAACATCTTGGTCCTACGAAAGGACATCGAAGATCTGAAGGCCCAGCTGCAGAATGCCAACAAGGTCATTCAAAACCTCAAGAGCCGGGTCCGGTCCCTCTCAGTTACAAGTGATTATTCGTCTAGTCTGGAAAGACCCCGGAAGCTGAGAGCTGTTGGCACCTTGGAGGGGTCTTCACCTCATAGTGTCCCTGATGAGGATGAGGGGTGGCTGTCTGATGGCACTGGGGCTTTCTACTCTCCAGGGCTTCAGGCCAAAAAGGACCTGGAGAGTCTCATCCAGAGAGTATCCCAGCTGGAGGCCCAGCTCCCAGAAAATGGACTAGAAGAGAAGCTGGCTGAGGAGCTGAGATCAGCCTCGTGGCCTGGGAAATATGATTCCCTGATTCAGGATCAGGCCCGGGAACTGTCTTACCTACGGCAAAAAATACGAGAAGGGAGAGGTATTTGTTATCTTATCACCCAGCATGCAAAAGATACAGTAAAATCTTTTGAGGATCTCCTAAGGAGCAATGACATTGACTACTACCTGGGACAGAGCTTCCGGGAGCAACTCGCCCAGGGAAGCCAGCTGACAGAGAGGCTCACCAGCAAACTCAGCACAGAGGATCATAAAAGTGAGAAAGATCAAGCTGGACTTGAGCCACTGGCCCTCAGGCTCAGCAGGGAGCTGCAGGAGAAGGAGAAAGTGATTGAAGTCCTGCAGGCCAAGCTGGATGCTCGGTCCCTCACACCCTCCAGCAGCCGTGCCTTGTCTGACTCCCACCGCTCTCCCAGCAGCACCTCTTTCCTGTCTGATGATCTGGAAGCCTGCTCTGACATGGACATAGTCAGCGAGTACACACACTATGAAGAGAAGAAAGCTTCTCCCAGTCACTCAGGTAGCAGTGCATCTCAGGGGGCTAAGGCCGAATCCAACAGCAACCCCATCAGCTTGCCAACTCCCCAGAATACCCCCAAGGAGGCCAACCAAGCCCATTCAGGCTTTCATTTTCACTCCATACCCAAGCTGGCTAGCCTTCCTCAGGCACCATTGCCCTCAGCTCCATCCAGCTTCCTGCCTTTCAGCCCCACTGGCCCTCCCCTCCTTGGCTGCTGTGAGACACCAGAGGTCTCCTTGGCTGAGTCTCAGCAGGAGCTACAGATGCTGCAGAAGCAGTTGGGAGAAAGTAGCACTGTTCCTCCTGCTTCCACAGCTACATTGCTGAGCAACGACTTGGAAGCCGACTCTTCCTACTACCTCAACTCTGCCCAGCCTCACTCTCCTCCAAGGGGCACCATAGAACTGGGAAGAATCCTAGAGCCTGGGTACCTGGGCAGCAGTGGCAAGTGGGATGTGATGAGGCCTCAGAAAGGGAGTGTATCTGGGGACCTATCCTCAGGCTCCTCTGTGTACCAGCTTAACTCCAAACCCACAGGGGCTGACCTGCTGGAAGAGCATCTTGGTGAAATCTGGAACCTGCGCCAGCGCCTGGAGGAGTCCATCTGCATCAATGACTGCCTACGGGAGCAACTGGAACACCGGCTGACCTCTACTGCTCGTGGAAGGGGATCCACTTCTAACTTCTACAGTCAGGGCCTGGAGTCCATACCTCAGCTCTGCAATGAGAACAGAGTCCTCAGGGAAGAAAATCGAAGACTTCAGGCTCAACTGAGTCATGTTTCCAGAGGTCACTCCCAGGAAACAGAAAGCCTGAGGGAGGCTCTGCTGTCCTCTCGATCCCACCTTCAAGAGCTGGAAAAGGAGCTGGAGCACCAGAAGGTGGAAAGGCAGCAGCTTTTGGAAGACTTGAGGGAGAAGCAGCAAGAGGTCTTGCATTTCAGGGAGGAACGTCTTTCCCTCCAGGAAAACGACTCCAGACTGCAGCACAAGCTGGTTCTCCTGCAGCAACAGTGTGAAGAGAAACAGCAGCTCTTTGAGTCCCTCCAGTCAGAGCTACAAATCTACGAGGCACTTTATGGCAATTCCAAGAAGGGGCTGAAAGCTTACAGCCTGGATGCCTGTCACCAAATCCCTTTGAGCAGTGACCTGAGCCACCTGGTGGCAGAGGTACAAGCTCTGAGAGGGCAGCTGGAGCAGAGCATTCAGGGGAACAATTGTCTGCGACTGCAGCTGCAACAGCAGCTGGAGAGCGGTGCTGGCAAAGCCAGCCTCAGCCCCTCCTCCATTAACCAGAACTTCCCAGCCAGCACTGACCCTGGAAACAAGCAGCTGCTCCTCCAAGGTTCAGCTGTGTCCCCTCCAGTCCGGGATGTTGGTATGAATTCCCCAGCTCTGGTCTTCCCCAGCTCTGCTTCCTCTACTCCTGGCTCAGATTCAGTTGTGTTGTCATTTTCTTTTTCAGGCTTGGGTTTGGATACTTCTCCAGTAATGAAGACCCCTCCCAAGCTAGAGGGTGATGCTACTGATGGCTCCTTTGCCAATAAGCATGGCCGCCATGTCATTGGCCACATTGATGACTACAGTGCCCTAAGACAGCAGATTGCGGAGGGCAAGCTGCTGGTCAAAAAGATAGTGTCTCTTGTGAGATCAGCGTGCAGCTTCCCTGGCCTTGAAGCCCAAGGCACAGAGGGCAGCAAAGGCATTCATGAGCTTCGGAGCAGCACCAGTGCCCTGCACCATGCCCTAGAGGAGTCGGCTTCCCTCCTCACCATGTTCTGGAGAGCGGCCCTGCCAAGCACCCACATCCCTGTGCTGCCTGGCAAACAGGGAGAATCAACAGAAAGGGAACTTCTGGAACTGAGAACCAAAGTATCCAAACAGGAGCAGCTCCTTCAGAGCACAACTGAGCATCTGAAGAACGCCAACCAGCAGAAGGAGAGCATGGAACAGTTCATTGTCAGCGTAACCAGAACACATGATGTTTTAAAGAAGGCAAGGACTAACTTAGAGGTGAAATCCCTAAGGGCTCTGCCGTGTACTCCAGCCTTGTGACCCTTGCCTTCCAGGAACCATGCAAGAAGCGCAGCCACCAGAAGTCCTTAAAACAGCAGGAAGGTGAGCCTGTCCCCCTTTTGTGCAGCTACCTATCTGCTGAGGAGCATCTGGGCCTCATTCCTCCAAGTORF Start: ATG at 46ORF Stop: TGA at 7027SEQ ID NO:2942327 aaMW at 263034.6 kDNOV103b,MSNGYRTLSQHLNDLKKENFSLKLRIYFLEERMQQKYEASREDIYKRNIELKVEVESLCG59773-02 ProteinSequenceKRELQDKKQHLDKTWADVENLNSQNEAELRRQFEERQQETEHVYELLENKIQLLQEESRLAKNEAARMAALVEAEKECNLELSEKLKGVTKNWEDVPGDQVKPDQYTEALAQRDRRIEELNQSLAAQERLVEQLSREKQQLLHLLEEPTSMEVQPMTEELLKQQKLNSHETTITQQSVSDSHLAELQEKIQQTEATNKILQEKLNEMSYELKCAQESSQKQDGTIQNLKETLKSRERETEELYQVIEGQNDTMAKLREMLHQSQLGQLQSSEGTSPAQQQVALLDLQSALFCSQLEIQKLQRVVRQKERQLADAKQCVQFVEAAAHESEQQKEASWKHNQELRKALQQLQEELQNKSQQLRAWEAEKYNEIRTQEQNIQHLNHSLSHKEQLLQEFRELLQYRDNSDKTLEANEMLLEKLRQRIHDKAVALERAIDEKFSALEEKEKELRQLRLAVRERDHDLERLRDVLSSNEATMQSMESLLRAKGLEVEQLSTTCQNLQWLKEEMETKFSRWQKEQESIIQQLQTSLHDRNKEVEDLSATLLCKLGPGQSEIAEELCQRLQRKERMLQDLLSDRNKQVLEHEMEIQGLLQSVSTREQESQAAAEKLVQALMERNSELQALRQYLGGRDSLMSQAPISNQQAEVTPTGRLGKQTDQGSMQIPSRDDSTSLTAKEDVSIPRSTLGDLDTVAGLEKELSNAKEELELMAKKERESQMELSALQSMMAVQEEELQVQAADMESLTRNIQIKEDLIKDLQMQLVDPEDIPAMERLTQEVLLLREKVASVESQGQEISGNRRQQQLLLMLEGLVDERSRLNEALQAERQLYSSLVKFHAHPESSERDRTLQVELEGAQVLRSRLEEVLGRSLERLNRLETLAAIGGAAAGDDTEDTSTEFTDSIEEEAAHHSHQQLVKVALEKSLATVETQNPSFSPPSPMGGDSNRCLQEEMLHLRAEIHQHLEEKRKAEEELKELKAQIEEAGFSSVSHIRNTMLSLCLENAELKEQMGETMSDGWEIEEDKEKGEVMVETVVTKEGLSESSLQAEFRKLQGKLKNAHNIINLLKEQLVLSSKEGNSKLTPELLVHLTSTIERINTELVGSPGKHQHQEEGNVTVRPFPRPQSLDLGATFTVDAHQQLDNQSQPRDPGPQPAFSLPGSTQHLRSQLSQCKQRYQDLQEKLLLSEATVFAQANELEKYRVMLSESLVKQDSKQIQVDFQDLGYETCGRSENEAEREETTSPECEEHNSLKEMVLMEGLCSEQGRRGSTLASSSERKPLENQLGKQEEFRVYGKSENILVLRKDIEDLKAQLQNANKVIQNLKSRVRSLSVTSDYSSSLERPRKLRAVGTLEGSSPHSVPDEDEGWLSDGTGAFYSPGLQAKKDLESLIQRVSQLEAQLPENGLEEKLAEELRSASWPGKYDSLIQDQARELSYLRQKIREGRGICYLITQHAKDTVKSFEDLLRSNDIDYYLGQSFREQLAQGSQLTERLTSKLSTEDHKSEKDQAGLEPLALRLSRELQEKEKVIEVLQAKLDARSLTPSSSRALSDSHRSPSSTSFLSDELEACSDMDIVSEYTHYEEKKASPSHSGSSASQGAKAESNSNPISLPTPQNTPKEANQAHSGFHFHSIPKLASLPQAPLPSAPSSFLPFSPTGPPLLGCCETPEVSLAESQQELQMLQKQLGESSTVPPASTATLLSNDLEADSSYYLNSAQPHSPPRGTIELGRILEPGYLGSSGKWDVMRPQKGSVSGDLSSGSSVYQLNSKPTGADLLEEHLGEIWNLRQRLEESICINDCLREQLEHRLTSTARGRGSTSNFYSQGLESIPQLCNENRVLREENRRLQAQLSHVSRGHSQETESLREALLSSRSHLQELEKELEHQKVERQQLLEDLREDQQEVLHFREERLSLQENDSRLQHKLVLLQQQCEEKQQLFESLQSELQIYEALYGNSKKGLKAYSLDACHQIPLSSDLSHLVAEVQALRGQLEQSIQGNNCLRLQLQQQLESGAGKASLSPSSINQNFPASTDPGNKQLLLQGSAVSPPVRDVGMNSPALVFPSSASSTPGSDSVVLSFSFSGLGLDTSPVMKTPPKLEGDATDGSFANKHGRHVIGHIDDYSALRQQIAEGKLLVKKIVSLVRSACSFPGLEAQGTEGSKGIHELRSSTSALHHALEESASLLTMFWRAALPSTHIPVLPGKQGESTERELLELRTKVSKQEQLLQSTTEHLKNANQQKESMEQFIVSVTRTHDVLKKARTNLEVKSLRALPCTPALSEQ ID NO:2957084 bpNOV103c,GTTGAGGGGGCAATCGGGCACGCTCCTCCCCATGGGTTGCCCATCATGTCTAATGGATCG59773-03 DNA SequenceATCGCACTCTGTCCCAGCACCTCAATGACCTGAAGAAGGAGAACTTCAGCCTCAAGCTGCTCATCTACTTCCTGGAGGAGCGCATGCAACAGAAGTATGAGGCCAGCCGGGAGGACATCTACAAGCGGGGGTGATGTGGAGAATCTCAACAGTCAGAATGAAGCTGAGCTCCGACGCCAGTTTGAGGAGCGACAGCAGGAGACGGAGCATGTTTATGAGCTCTTGGAGAATAAGATCCAGCTTCTGCAGGAGGAATCCAGGCTAGCAAAGAATGAAGCTGCGCGGATGGCAGCTCTGGTGGAAGCAGAGAAGGAGTGTAACCTGGAGCTCTCAGAGAAACTGAAGGGAGTCACCAAAAACTGGGAAGATGTACCAGGAGACCAGGTCAAGCCCGACCAATACACTGAGACCCTGGCCCAGAGGGACAAGAGAATTGAAGAACTGAATCAGAGCCTGGCTGCCCAGGAGAGGCTTGTAGAACAGCTATCTCGGGAGAAACAACAACTGCTACATCTGTTGGAGGAGCCAACTAGCATGGAAGTGCAGCCCATGACTGAAGAGTTGCTGAAACAACAAAAGCTGAATTCACATGAGACCACTATAACTCAGCAGTCTGTATCTGATTCCCACTTGGCAGAACTCCAGGAAAAAATCCAGCAAACAGAGGCCACCAACAAGATTCTTCAAGAGAAACTTAATGAAATGAGCTATGAACTAAAGTGTGCTCAGGAGTCGTCTCAAAAGCAAGATGGTACAATTCAGAACCTCAAGGAAACTCTGAAAAGCAGGGAACGTGAGACTGAGGAGTTGTACCAGGTAATTGAAGGTCAAAATGACACAATGGCAAAGCTTCGAGAAATGCTGCACCAAAGCCAGCTTGGACAACTTCAGAGCTCAGAGGGTACTTCTCCAGCTCAGCAACAGGTAGCTCTGCTTGATCTTCAGAGTGCTTTATTCTGCAGCCAACTTGAAATACAGAAGCTCCAGAGGGTGGTACGACAGAAAGAGCGCCAACTGGCTGATGCCAAACAATGTGTGCAATTTGTAGAGGCTGCAGCACACGAGAGTGAACAGCAGAAAGAGGCTTCTTGGAAACATAACCAGGAATTGCGAAAAGCCTTGCAGCAGCTACAAGAAGAATTGCAGAATAAGAGCCAACAGCTTCGTGCCTGGGAGGCTGAAAAATACAATGAGATTCGAACCCAGGAACAAAACATCCAGCACCTAAACCATAGTCTGAGTCACAAGGAGCAGTTGCTTCAGGAATTTCGGGAGCTCCTACAGTATCGAGATAACTCAGACAAAACCCTTGAAGCAAATGAAATGTTGCTTGAGAAACTTCGCCAGCGAATACATGATAAAGCTGTTGCTCTGGAGCGGGCTATAGATGAAAAATTCTCTGCTCTAGAAGAGAAAGAAAAAGAACTGCGCCAGCTTCGTCTTGCTGTGAGAGAGCGAGATCATGACTTAGAGAGACTGCGCGATGTCCTCTCCTCCAATGAAGCTACTATGCAAAGTATGGAGAGTCTCCTGAGGGCCAAAGGCCTGGAAGTGGAACAGTTATCTACTACCTGTCAAAACCTCCAGTGGCTGAAAGAAGAAATGGAAACCAAATTTAGCCGTTGGCAGAAGGAACAAGAGAGTATCATTCAGCAGTTACAGACGTCTCTTCATGATAGGAACAAAGAAGTGGAGGATCTTAGTGCAACACTGCTCTGCAAACTTGGACCAGGGCAGAGTGAGATAGCAGAGGAGCTGTGCCAGCGTCTACAGCGAAAGGAAAGGATGCTGCAGGACCTTCTAAGTGATCGAAATAAACAAGTGCTGGAACATGAAATGGAGATTCAAGGCCTGCTTCAGTCTGTGAGCACCAGGGAGCAGGAAAGCCAAGCTGCTGCAGAGAAGTTGGTGCAAGCCTTAATGGAAAGAAATTCAGAATTACAGGCCCTGCGCCAATATTTAGGAGGGAGAGACTCCCTGATGTCCCAAGCACCCATCTCTAACCAACAAGCTGAAGTTACCCCCACTGGCCGTCTTGGAAAACAGACTGATCAAGGTTCAATGCAGATACCTTCCAGAGATGATAGCACTTCATTGACTGCCAAAGAGGATGTCAGCATACCCAGATCCACATTAGGAGATTTGGACACAGTTGCAGGGCTGGAAAAAGAACTGAGTAATGCCAAAGAGGAACTTGAACTCATGGCTAAAAAAGAAAGAGAATCACAGATGGAACTTTCTGCTCTACAGTCCATGATGGCTGTGCAGGAAGAAGAGCTGCAGGTGCAGGCTGCTGATATGGAGTCTCTGACCAGGAACATACAGATTAAAGAAGATCTCATAAAGGACCTGCAAATGCAACTGGTTGATCCTGAAGACATACCAGCTATGGAACGCCTGACCCAGGAAGTCTTACTTCTTCGGGAAAAAGTTGCTTCAGTAGAATCCCAGGGTCAAGAAATTTCAGGAAACCGAAGACAACAGCAGTTGCTGCTGATGCTAGAAGGACTAGTAGATGAACGGAGTCGGCTCAATGAGGCCTTACAAGCAGAGAGACAGCTCTATAGCAGTCTGGTGAAGTTCCATGCCCATCCAGAGAGCTCTGAGAGAGACCGAACTCTGCAGGTGGAACTGGAAGGGGCTCAGGTGTTACGCAGTCGGCTAGAAGAACTTCTTGGAAGAAGCTTGGAGCGCTTAAACAGGCTGGAGACCCTGGCCGCCATTGGAGGTGCAGCTGCAGGGGATGACACCGAAGATACAAGCACTGAGTTCACTGACAGTATTGAGGAGGAGGCTGCACACCATAGTCACCAGCAACTTGTCAAGGTGGCTTTGGAGAAAAGTCTGGCAACTGTGGAGACCCAGAACCCATCTTTTTCCCCTCCTTCTCCGATGGGAGGGGACAGTAACAGGTGTCTTCAGGAAGAAATGCTCCACCTGAGGGCTGAGATCCACCAGCACTTAGAAGAGAAGAGGAAAGCTGAGGAGGAACTGAAGGAGCTAAAGGCTCAAATTGAGGAAGCAGGATTCTCCTCAGTGTCCCACATCAGGAACACCATGCTGAGCCTTTGCCTTGAGAATGCGGAGCTGAAAGAGCAGATGGGAGAAACAATGTCTGATGGATGGGAGATCGAGGAAGACAAGGAGAAGGGCGAGGTGATGGTTGAGACTGTGGTAACCAAAGAGGGTCTGAGTGAGAGTAGCCTTCAGGCTGAGTTCAGAAAGCTCCAGGGAAAACTGAAGAATGCCCACAATATCATCAACCTCCTCAAAGAACAACTTGTGCTGAGTAGCAAGGAAGGGAATAGTAAACTTACTCCAGAGCTCCTTGTGCATCTGACCAGCACCATCGAAAGAATAAACACAGAACTGGTTGGTTCCCCTGGGAAGCACCAACACCAAGAGGAGGGGAATGTGACTGTGAGGCCTTTCCCCAGACCCCAGAGCCTTGACCTTGGGGCTACCTTCACAGTGGATGCCCACCAACAGTTGGATAACCAGTCCCAGCCTCGTGACCCTGGGCCTCAGCCAGCGTTTAGCCTACCAGGGTCCACCCAGCACCTGCGCTCCCAGCTGTCACAATGCAAACAACGCTATCAAGATCTCCAGGAGAAGCTGCTGCTATCAGAAGCCACTGTCTTTGCTCAGGCTAACGAGCTGGAGAAATACAGAGTTATGCTTAGTGAATCCTTGGTGAAGCAGGACAGCAAGCAGATCCAGGTGGACTTCCAGGACCTGGGCTATGAGACTTGTGGCCGAAGCGAGAATGAGGCTGAACGGGAGGAAACCACCAGTCCTGAGTGTGAGGAGCACAACAGCCTCAAGGAAATGGTCCTGATGGAGGGGCTGTGCTCTGAGCAGGGACGCCGGGGCTCAACACTGGCTAGTTCCTCTGAGAGGAAGCCCTTGGAGAACCAGCTAGGGAAGCAGGAAGAGTTCCGGGTATATGGAAAGTCAGAAAACATCTTGGTCCTACGAAAGGACATCGAAGATCTGAAGGCCCAGCTGCAGAATGCCAACAAGGTCATTCAAAACCTCAAGAGCCGGGTCCGGTCCCTCTCAGTTACAAGTGATTATTCGTCTAGTCTGGAAAGACCCCGGAAGCTGAGAGCTGTTGGCACCTTGGAGGGGTCTTCACCTCATAGTGTCCCTGATGAGGATGAGGGGTGGCTGTCTGATGGCACTGGGGCTTTCTACTCTCCAGGGCTTCAGGCCAAAAAGGACCTGGAGAGTCTCATCCAGAGAGTATCCCAGCTGGAGGCCCAGCTCCCAGAAAATGGACTAGAAGAGAAGCTGGCTGAGGAGCTGAGATCAGCCTCGTGGCCTGGGAAATATGATTCCCTGATTCAGGATCAGGCCCGGGAACTGTCTTACCTACGGCAAAAAATACGAGAAGGGAGAGGTATTTGTTATCTTATCACCCAGCATGCAAAAGATACAGTAAAATCTTTTGAGGATCTCCTAAGGAGCAATGACATTGACTACTACCTGGGACAGAGCTTCCGGGAGCAACTCGCCCAGGGAAGCCAGCTGACAGAGAGGCTCACCAGCAAACTCAGCACAGAGGATCATAAAAGTGAGAAAGATCAAGCTGGACTTGAGCCACTGGCCCTCAGGCTCAGCAGGGAGCTGCAGGAGAAGGAGAAAGTGATTGAAGTCCTGCAGGCCAAGCTGGATGCTCGGTCCCTCACACCCTCCAGCAGCCGTGCCTTGTCTGACTCCCACCGCTCTCCCAGCAGCACCTCTTTCCTGTCTGATGAGCTGGAAGCCTGCTCTGACATGGACATAGTCAGCGAGTACACACACTATGAAGAGAAGAAAGCTTCTCCCAGTCACTCAGGTAGCAGTGCATCTCAGGGGGCTAAGGCCGAATCCAACAGCAACCCCATCAGCTTGCCAACTCCCCAGAATACCCCCAAGGAGGCCAACCAAGCCCATTCAGGCTTTCATTTTCACTCCATACCCAAGCTGGCTAGCCTTCCTCAGGCACCATTGCCCTCAGCTCCATCCAGCTTCCTGCCTTTCAGCCCCACTGGCCCTCCCCTCCTTGGCTGCTGTGAGACACCAGAGGTCTCCTTGGCTGAGTCTCAGCAGGAGCTACAGATGCTGCAGAAGCAGTTGGGAGAAAGTAGCACTGTTCCTCCTGCTTCCACAGCTACATTGCTGAGCAACGACTTGGAAGCCGACTCTTCCTACTACCTCAACTCTGCCCAGCCTCACTCTCCTCCAAGGGGCACCATAGAACTGGGAAGAATCCTAGAGCCTGGGTACCTGGGCAGCAGTGGCAAGTGGGATGTGATGAGGCCTCAGAAAGGGAGTGTATCTGGGGACCTATCCTCAGGCTCCTCTGTGTACCAGCTTAACTCCAAACCCACAGGGGCTGACCTGCTGGAAGAGCATCTTGGTGAAATCTGGAACCTGCGCCAGCGCCTGGAGGAGTCCATCTGCATCAATGACTGCCTACGGGAGCAACTGGAACACCGGCTGACCTCTACTGCTCGTGGAAGGGGATCCACTTCTAACTTCTACAGTCAGGGCCTGGAGTCCATACCTCAGCTCTGCAATGAGAACAGAGTCCTCAGGGAAGAAAATCGAAGACTTCAGGCTCAACTGAGTCATGTTTCCAGAGGTCACTCCCAGGAAACAGAAAGCCTGAGGGAGGCTCTGCTGTCCTCTCGATCCCACCTTCAAGAGCTGGAAAAGGAGCTGGAGCACCAGAAGGTGGAAAGGCAGCAGCTTTTGGAAGACTTGAGGGAGAAGCAGCAAGAGGTCTTGCATTTCAGGGAGGAACGTCTTTCCCTCCAGGAAAACGACTCCAGACTGCAGCACAAGCTGGTTCTCCTGCAGCAACAGTGTGAAGAGAAACAGCAGCTCTTTGAGTCCCTCCAGTCAGAGCTACAAATCTACGAGGCACTTTATGGCAATTCCAAGAAGGGGCTGAAAGCTTACAGCCTGGATGCCTGTCACCAAATCCCTTTGAGCAGTGACCTGAGCCACCTGGTGGCAGAGGTACAAGCTCTGAGAGGGCAGCTGGAGCAGAGCATTCAGGGGAACAATTGTCTGCGACTGCAGCTGCAACAGCAGCTGGAGAGCGGTGCTGGCAAAGCCAGCCTCAGCCCCTCCTCCATTAACCAGAACTTCCCAGCCAGCACTGACCCTGGAAACAAGCAGCTGCTCCTCCAAGGTTCAGCTGTGTCCCCTCCAGTCCGGGATGTTGGTATGAATTCCCCAGCTCTGGTCTTCCCCAGCTCTGCTTCCTCTACTCCTGGCTCAGATTCAGTTGTGTTGTCATTTTCTTTTTCAGGCTTGGGTTTGGATACTTCTCCAGTAATGAAGACCCCTCCCAAGCTAGAGGGTGATGCTACTGATGGCTCCTTTGCCAATAAGCATGGCCGCCATGTCATTGGCCACATTGATGACTACAGTGCCCTAAGACAGCAGATTGCGGAGGGCAAGCTGCTGGTCAAAAAGATAGTGTCTCTTGTGAGATCAGCGTGCAGCTTCCCTGGCCTTGAAGCCCAAGGCACAGAGGGCAGCAAAGGCATTCATGAGCTTCGGAGCAGCACCAGTGCCCTGCACCATGCCCTAGAGGAGTCGGCTTCCCTCCTCACCATGTTCTGGAGAGCGGCCCTGCCAAGCACCCACATCCCTGTGCTGCCTGGCAAACAGGGAGAATCAACAGAAAGGGAACTTCTGGAACTGAGAACCAAAGTATCCAAACAGGAGCAGCTCCTTCAGAGCACAACTGAGCATCTGAAGAACGCCAACCAGCAGAAGGAGAGCATGGAACAGTTCATTGTCAGCGTAACCAGAACACATGATGTTTTAAAGAAGGCAAGGACTAACTTAGAGGTGAAATCCCTAAGGGCTCTGCCGTGTACTCCAGCCTTGTGACCCTTGCCTTCCAGGAACCATGCAAGAAGCGCAGCCACCAGAAGTCCTTAAAACAGCAGGAAAGGTGAGCCTGTCCCCCTTTTGTGCAGCTACCTATCTGCTGAGGAGCATCTGGGCCTCATTCCTCCAAGTORF Start: ATG at 155ORF Stop: TGA at 6950SEQ ID NO:2962265 aaMW at 255081.5 kDNOV103c,MRPAGRTSTSGGDVENLNSQNEAELRRQFEERQQETEHVYELLENKIQLLQEESRLAKCG59773-03 ProteinSequenceNEAARMAALVEAEKECNLELSEKLKGVTKNWEDVPGDQVKPDQYTETLAQRDKRIEELNQSLAAQERLVEQLSREKQQLLHLLEEPTSMEVQPMTEELLKQQKLNSHEETTITQQSVSDSHLAELQEKIQQTEATNKILQEKLNEMSYELKCAQESSQKQDGTIQNLKETLKSRERETEELYQVIEGQNDTMAKLREMLHQSQLGQLHSSEGTSPAQQQVALLDLQSALFCSQLEIQKLQRVVRQKERQLADAKQCVQFVEAAAHESEQQKEASWKHNQELRKALQQLQEELQNKSQQLRAWEAEKYNEIRTQEQNIQHLNHSLSHKEQLLQEFRELLQYRDNSDKTLEANEMLLEKLRQRIHDKAVALERAIDEKFSALEEKEKELRQLRLAVRERDHDLERLRDVLSSNEATMQSMESLLRAKGLEVEQLSTTCQNLQWLKEEMETKFSRWQKEQESIIQQLQTSLHDRNKEVEDLSATLLCKLGPGQSEIAEELCQRLQRKERMLQDLLSDRNKQVLEHEMEIQGLLQSVSTREQESQAAAEKLVQALMERNSELQALRQYLGGRDSLMSQAPISNQQAEVTPTGRLGKQTDQGSMQIPSRDDSTSLTAKEDVSIPRSTLGDLDTVAGLEKELSNAKEELELMAKKERESQMELSALQSMMAVQEEELQVQAADMESLTRNIQIKEDLIKDLQMQLVDPEDIPAMERLTQEVLLLREKVASVESQGQEISGNRRQQQLLLMLEGLVDERSRLNEALQAERQLYSSLVKFHAHPESSERDRTLQVELEGAQVLRSRLEEVLGRSLERLNRLETLAAIGGAAAGDDTEDTSTEFTDSIEEEAAHHSHQQLVKVALEKSLATVETQNPSFSPPSPMGGDSNRCLQEEMLHLRAEFHQHLEEKRKAEEELKELKAQIEEAGFSSVSHIRNTMLSLCLENAELKEQMGEAMSDGWEIEEDKEKGEVMVETVVTKEGLSESSLQAEFRKLQGKLKNAHNIINLLKEQLVLSSKEGNSKLTPELLVHLTSTIERINTELVGSPGKHQHQEEGNVTVRPFPRPQSLDLGATFTVDAHQQLDNQSQPRDPGPQSAFSLPGSTQHLRSQLSQCKQRYQDLQEKLLLSEATVFAQANELEKYRVMLSESLVKQDSKQIQVDFQDLGYETCGRSENEAEREETTSPECEEHNSLKEMVLMEGLCSEQGRRGSTLASSSERKPLENQLGKQEEFRVYGKSENILVLRKDIEDLKAQLQNANKVIQNLKSRVRSLSVTSDYSSSLERPRKLRAVGTLEGSSPHSVPDEDEGWLSDGTGAFYSPGLQAKKDLESLIQRVSQLEAQLPENGLEEKLAEELRSASWPGKYDSLIQDQARELSYLRQKIREGRGICYLITQHAKDTVKSFEDLLRSNDIDYYLGQSFREQLAQGSQLTERLTSKLSTEDHKSEKDQAGLEPLALRLSRELQEKEKVIEVLQAKLDARSLTPSSSRALSDSHRSPSSTSFLSDELEACSDMDIVSEYTHYEEKKASPSHSGSSASQGAKAESNSNPISLPTPQNTPKEANQAHSGFHFHSIPKLASLPQAPLPSAPSSFLPFSPTGPPLLGCCETPEVSLAESQQELQMLQKQLGESSTVPPASTATLLSNDLEADSSYYLNSAQPHSPPRGTIELGRILEPGYLGSSGKWDVMRPQKGSVSGDLSSGSSVYQLNSKPTGADLLEEHLGEIWNLRQRLEESICINDCLREQLEHRLTSTARGRGSTSNFYSQGLESIPQLCNENRVLREENRRLQAQLSHVSRGHSQETESLREALLSSRSHLQELEKELEHQKVERQQLLEDLREKQQEVLHFREERLSLQENDSRLQHKLVLLQQQCEEKQQLFESLQSELQIYEALYGNSKKGLKAYSLDACHQIPLSSDLSHLVAEVQALRGQLEQSIQGNNCLRLQLQQQLESGAGKASLSPSSINQNFPASTDPGNKQLLLQGSAVSPPVRDVGMNSPALVFPSSASSTPGSDSVVLSFSFSGLGLDTSPVKMTPPKLEGDATDGSFANKHGRHVIGHIDDYSALRQQIAEGKLLVKKIVSLVRSACSFPGLEAQGTEGSKGIHELRSSTSALHHALEESASLLTMFWRAALPSTHIPVLPGKQGESTERELLELRTKVSKQEQLLQSTTEHLKNANQQKESMEQFIVSVTRTHDVLKKARTNLEVKSLRARPCTPAL


[0864] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 103B.
540TABLE 103BComparison of NOV103a against NOV103b through NOV103c.Identities/SimilaritiesProteinNOV103a Residues/for theSequenceMatch ResiduesMatched RegionNOV103b365 . . . 21961510/1834 (82%)202 . . . 20161518/1834 (82%)NOV103c365 . . . 21961510/1834 (82%)140 . . . 19541518/1834 (82%)


[0865] Further analysis of the NOV103a protein yielded the following properties shown in Table 103C.
541TABLE 103CProtein Sequence Properties NOV103aPSort0.5855 probability located in mitochondrial matrix space;analysis:0.4200 probability located in nucleus; 0.3000 probabilitylocated in microbody (peroxisome); 0.2957 probability locatedin mitochondrial inner membraneSignalPLikely cleavage site between residues 39 and 40analysis:


[0866] A search of the NOV103a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 103D.
542TABLE 103DGeneseq Results for NOV103aNOV103aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAY71159Human phosphodiesterase 1 . . . 21962193/2204 (99%)0.0interacting protein, myomegalin- 1 . . . 22042193/2204 (99%)Homo sapiens, 2517 aa.[WO200027861-A1,18 MAY 2000]AAM40183Human polypeptide SEQ ID NO635 . . . 21961557/1570 (99%)0.03328-Homo sapiens, 1883 aa. 1 . . . 15701559/1570 (99%)[WO200153312-A1,26 JUL. 2001]AAY71158phosphodiesterase interacting365 . . . 21971433/1837 (78%)0.0protein, myomegalin-Rattus sp,202 . . . 20171572/1837 (85%)2326 aa. [WO200027861-A1,18 MAY 2000]AAY67600Human adipose tissue protein #3- 1 . . . 934925/934 (99%)0.0Homo sapiens, 944 aa. 1 . . . 934927/934 (99%)[JP2000037190-A, 8 FEB. 2000]AAU01768Human secreted protein #47-365 . . . 1102730/738 (98%)0.0Homo sapiens, 934 aa.197 . . . 934733/738 (98%)[WO200123546-A1, 5 APR. 2001]


[0867] In a BLAST search of public sequence databases, the NOV103a protein was found to have homology to the proteins shown in the BLASTP data in Table 103E.
543TABLE 103EPublic BLASTP Results for NOV103aNOV103aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueO75042KIAA0454 PROTEIN-Homo636 . . . 21961558/1569 (99%)0.0sapiens (Human), 1882 aa 1 . . . 15691558/1569 (99%)(fragment).Q9WUJ3MYOMEGALIN-Rattus365 . . . 21971444/1838 (78%)0.0norvegicus (Rat), 2324 aa.202 . . . 20151581/1838 (85%)O75065KIAA0477 PROTEIN-Homo 1 . . . 11321132/1132 (100%)0.0sapiens (Human), 1132 aa. 1 . . . 11321132/1132 (100%)Q25893LIVER STAGE ANTIGEN-356 . . . 1459 243/1129 (21%)4e−35Plasmodium falciparum (isolate605 . . . 1651 488/1129 (42%)NF54), 1909 aa.Q13439Golgi autoantigen, golgin229 . . . 1749 349/1638 (21%)4e−34subfamily A 4 (Trans-Golgi p230)267 . . . 1814 679/1638 (41%)(256 kDa golgin) (Golgin-245)(72.1 protein)-Homo sapiens(Human), 2230 aa.


[0868] PFam analysis predicts that the NOV103a protein contains the domains shown in the Table 103F.
544TABLE 103FDomain Analysis of NOV103aIdentities/PfamNOV103aSimilarities forExpectDomainMatch Regionthe Matched RegionValueSomatomedin_B: 150 . . . 189 14/47 (30%)7.6domain 1 of 1 25/47 (53%)necA: domain 1 of 1 621 . . . 650 8/30 (27%)8.1 22/30 (73%)Ribosomal_L10: 604 . . . 695 20/109 (18%)9.9domain 1 of 1 59/109 (54%)Dishevelled: 844 . . . 914 19/74 (26%)2.7domain 1 of 1 37/74 (50%)Transposase_22:1135 . . . 1416 71/376 (19%)4.6domain 1 of 1127/376 (34%)Phe_tRNA-synt_N:2079 . . . 2152 13/79 (16%)4.9domain 1 of 1 49/79 (62%)



Example 104

[0869] The NOV104 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 104A.
545TABLE 104ANOV104 Sequence AnalysisSEQ ID NO:297736 bpNOV104a,AAAGCACCCGAGATGACCCCGGCTCCTCCACCAGGAGCGCGGCCGGGCGCGGCGTCCCCG57460-01 DNA SequenceTAGCGGGCTTCGCCGGGGTGGCGTCTCTGGGGCCTGGGGACCCCCGCCGCGCCGCTGACCCGCGCCCTCTGCCCCCAGCGCTGTGCTTCGCCGTGAGCCGCTCGCTGCTGCTGACGTGCCTGGTGCCGGCCGCGCTGCTGGGCCTGCGCTACTACTACAGCCGCAAGGTGATCCGCGCCTACCTGGAGTGCGCGCTGCACACGGACATGGCGGACATCGAGCAGTACTACATGAAGCCGCCCGGTGTGTCCCTGACCGCCCTATCCCCTGCAGGCTCCTGCTTCTGGGTGGCCGTGCTGGATGGCAACGTGGTGGGCATTGTGGCTGCACGGGCCCACGAGGAGGACAACACGGTGGAGCTGCTGCGGATGTCTGTGGACTCACGTTTCCGAGGCAAGGGCATCGCCAAGGCGCTGGGCCGGAAGGTGCTGGAGTTCGCCGTGGTGCACAACTACTCCGCGGTGGTGCTGGGCACGACGGCCGTCAAGGTGGCCGCCCACAAGCTCTACGAGTCGCTGGGCTTCAGACACATGGGCGCCAGTGACCACTACGTGCTGCCGGGCATGACCCTCTCGCTGGCTGAGCGCCTCTTCTTCCAGGTCCGCTACCACCGCTACCGCCTGCAGCTGCGCGAGGAGTGACCGCCGCCGCTCGCCCGCCCGCCCCCCCGGCCGCCCTORF Start: ATG at 13ORF Stop: TGA at 697SEQ ID NO:298228 aaMW at 24767.5 kDNOV104a,MTPAPPPGARPGAASLAGFAGVASLGPGDPRRAADPRPLPPALCFAVSRSLLLTCLVPCG57460-01 Protein SequenceAALLGLRYYYSRKVIRAYLECALHTDMADIEQYYMKPPGVSLTALSPAGSCFWVAVLDGNVVGIVAARAHEEDNTVELLRMSVDSRFRGKGIAKALGRKVLEFAVVHNYSAVVLGTTAVKVAAHKLYESLGFRHMGASDHYVLPGMTLSLAERLFFQVRYHRYRLQLREE


[0870] Further analysis of the NOV104a protein yielded the following properties shown in Table 104B.
546TABLE 104BProtein Sequence Properties NOV104aPSort0.6400 probability located in plasma membrane; 0.4600analysis:probability located in Golgi body; 0.3700 probabilitylocated in endoplasmic reticulum (membrane); 0.1000probability located in endoplasmic reticulum (lumen)SignalPLikely cleavage site between residues 64 and 65analysis:


[0871] A search of the NOV104a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 104C.
547TABLE 104CGeneseq Results for NOV104aNOV104aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAB19986Human camello 3 (Hcml3) protein42 . . . 195144/154 (93%)7e−76(partial)-Homo sapiens, 144 aa. 1 . . . 144144/154 (93%)[WO200077024-A1,21 DEC. 2000]AAB19985Human camello 2 (Hcml2) protein-47 . . . 200 63/158 (39%)1e−21Homo sapiens, 227 aa.56 . . . 203 92/158 (57%)[WO200077024-A1,21 DEC. 2000]AAB19984Human camello 1 (Hcml1) protein-41 . . . 196 60/160 (37%)7e−20Homo sapiens, 227 aa.50 . . . 199 88/160 (54%)[WO200077024-A1,21 DEC. 2000]AAY57959Human TSC501 protein SEQ ID41 . . . 196 59/160 (36%)4e−19NO: 1-Homo sapiens, 227 aa.50 . . . 199 87/160 (53%)[JP11332579-A, 7 DEC. 1999]AAB19987Mouse camello 1 (Mcml1)41 . . . 194 63/158 (39%)1e−18protein-Mus sp, 222 aa.50 . . . 197 87/158 (54%)[WO200077024-A1,21 DEC. 2000]


[0872] In a BLAST search of public sequence databases, the NOV104a protein was found to have homology to the proteins shown in the BLASTP data in Table 104D.
548TABLE 104DPublic BLASTP Results for NOV104aNOV104aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueQ9UHF3PUTATIVE N-47 . . . 20063/158 (39%)5e−21ACETYLTRANSFERASE56 . . . 20392/158 (57%)CAMELLO 2-Homo sapiens(Human), 227 aa.Q9UHE5PUTATIVE N-41 . . . 19660/160 (37%)3e−19ACETYLTRANSFERASE CML1-50 . . . 19988/160 (54%)Homo sapiens (Human), 227 aa.Q9UQ17GLA PROTEIN-Homo sapiens41 . . . 19660/160 (37%)3e−19(Human), 227 aa.50 . . . 19988/160 (54%)Q96QI8KIDNEY-AND LIVER-SPECIFIC41 . . . 19659/160 (36%)1e−18GENE -Homo sapiens (Human),50 . . . 19987/160 (53%)227 aa.O75839TSC501 PROTEIN-Homo41 . . . 19659/160 (36%)1e−18sapiens (Human), 227 aa.50 . . . 19987/160 (53%)


[0873] PFam analysis predicts that the NOV104a protein contains the domains shown in the Table 104E.
549TABLE 104EDomain Analysis of NOV104aIdentities/PfamNOV104aSimilarities forExpectDomainMatch Regionthe Matched RegionValueAcetyltransf: domain 1111 . . . 19128/82 (34%)2.2e−17of 164/82 (78%)



Example 105

[0874] The NOV105 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 105A.
550TABLE 105ANOV105 Sequence AnalysisSEQ ID NO:2991230 bpNOV105a,CTTCCCGGCGGCTGCGCGATGGACAGCCCCGAGGTGACCTTCACTCTCGCCTATCTGGCG57464-01 DNA SequenceTGTTCGCCGTGTGCTTCGTGTTCACGCCCAACGAGTTCCACGCGGCGGGGCTCACGGTGCAGAACCTGCTGTCGGGCTGGCTGGGCAGCGAGGACGCCGCCTTCGTGCCCTTCCACTTGCGCCGCACGGCCGCCACGCTGTTGTGCCACTCGCTGCTGCCGCTCGGTGAGGCTGCTCGGGCCGGCCGGCCGCATCCTCTCCTGCGCAGGGCTTGCTGGGAGGTCAGGAGGAGGCCTCCGCCAGCTCCCCGAGGCCCCGAAAGCGCCTGGGCGCAGCTGGGGAGAGGCGCCGGTCCTCATCCAGAGGGACCGCGGCGTGGGCTGAGCGCGCTTAGGGGTGCCGCCGGCCTGGCCTGGCGGCTCTTCCTGCTGCTGGCCGTGACCCTCCCCTCCATCGCCTGCATCCTGATCTACTACTGGTCCCGTGACCGGTGGGCCTGCCACCCACTGGCGCGCACCCTGGCCCTCTACGCCCTCCCACAGTCTGGCTGGCAGGCTGTTGCCTCCTCTGTCAACACTGAGTTCCGGCGGATTGACAAGTTTGCCACCGGTGCACCAGGTGCCCGTGTGATTGTGACAGACACGTGGGTGATGAAGGTAACCACCTACCGAGTGCACGTGGCCCAGCAGCAGGACGTGCACCTGACTGTGACGGAGTCTCGGCAGCATGAGCTCTCGCCAGACTCGAACTTGCCCGTGCAGCTCCTCACCATCCGTGTGGCCAGCACCAACCCTGCTGTGCAGGCCTTTGACATCAGGCTGAACTCCACTGAGTACGGGGAGCTCTGCGAGAAGCTCCGGGCACCCATCCGCAGGGCAGCCCATGTGGTCATCCACCAGAGCCTGGGCGACCTGTTCCTGGAGACATTTGCCTCCCTGGTAGAGGTCAACCCGGCCTACTCAGTGCCCAGCAGCCAGGTGGGGGGCCTGGAGGCCTGCATAGGCTGCATGCAGACACGTGCCAGCGTGAAGCTGGTGAAGACCTGCCAGGAGGCAGCCACAGGCGAGTGCCAGCAGTGTTACTGCCGCCCCATGTGGTGCCTCACCTGCATGGGCAAGTGGTTCGCCAGCCGCCAGGACCCCCTGCGCCCTGACACCTGGCTGGCCAGCCGCGTGCCCTGCCCCACCTGCCGCGCACGCTTCTGCATCCTGGATGTGTGCACCGTGCGCTGAORF Start: ATG at 19ORF Stop: TGA at 1228SEQ ID NO:300403 aaMW at 44585.0 kDNOV105a,MDSPEVTFTLAYLVFAVCFVFTPNEFHAAGLTVQNLLSGWLGSEDAAFVPFHLRRTAACG57464-01 Protein SequenceTLLCHSLLPLGEAARAGRPHPLLRRACWEVRRRPPPAPRGPESAWAQLGRGAGPHPEGPRRGLSALRGAAGLAWRLFLLLAVTLPSIACILIYYWSRDRWACHPLARTLALYALPQSGWQAVASSVNTEFRRIDKFATGAPGARVIVTDTWVMKVTTYRVHVAQQQDVHLTVTESRQHELSPDSNLPVQLLTIRVASTNPAVQAFDIRLNSTEYGELCEKLRAPIRRAAHVVIHQSLGDLFLETFASLVEVNPAYSVPSSQVGGLEACIGCMQTRASVKLVKTCQEAATGECQQCYCRPMWCLTCMGKWFASRQDPLRPDTWLASRVPCPTCRARFCILDVCTVR


[0875] Further analysis of the NOV105a protein yielded the following properties shown in Table 105B.
551TABLE 105BProtein Sequence Properties NOV105aPSort0.6760 probability located in plasma membrane; 0.1000analysis:probability located in endoplasmic reticulum (membrane);0.1000 probability located in endoplasmic reticulum (lumen);0.1000 probability located in outsideSignalPLikely cleavage site between residues 29 and 30analysis:


[0876] A search of the NOV105a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 105C.
552TABLE 105CGeneseq Results for NOV105aNOV105aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAG81377Human AFP protein sequence SEQ1 . . . 403344/409 (84%)0.0ID NO: 272-Homo sapiens, 3621 . . . 362345/409 (84%)aa. [WO200129221-A2,26 APR. 2001]


[0877] In a BLAST search of public sequence databases, the NOV105a protein was found to have homology to the proteins shown in the BLASTP data in Table 105D.
553TABLE 105DPublic BLASTP Results for NOV105aNOV105aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueCAC38627SEQUENCE 271 FROM 1 . . . 403345/409 (84%)0.0PATENT WO0129221-Homo 1 . . . 362346/409 (84%)sapiens (Human), 362 aa.Q9DCF30610039G24RIK PROTEIN- 1 . . . 403311/403 (77%) e−176Mus musculus (Mouse), 362 aa. 1 . . . 362328/403 (81%)Q96GP5SIMILAR TO RIKEN CDNA 1 . . . 265211/271 (77%) e−1090610039G24 GENE-Homo 1 . . . 226212/271 (77%)sapiens (Human), 232 aa.Q9VN16CG14646 PROTEIN-Drosophila 1 . . . 399123/409 (30%)1e−55melanogaster (Fruit fly), 409 aa. 1 . . . 383202/409 (49%)Q95TM4LD39811P-Drosophila20 . . . 399117/390 (30%)1e−51melanogaster (Fruit fly), 393 aa. 4 . . . 367192/390 (49%)


[0878] PFam analysis predicts that the NOV105a protein contains the domains shown in the Table 105E.
554TABLE 105EDomain Analysis of NOV105aIdentities/PfamNOV105aSimilarities forExpectDomainMatch Regionthe Matched RegionValueNo Significant Matches Found



Example 106

[0879] The NOV106 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 106A.
555TABLE 106ANOV106 Sequence AnalysisSEQ ID NO:3011136 bpNOV106a,TTTCTGCAATGGGAGCCTCCGCCACCCACCCTGGAGCCACAGAAGGCCCAGAAGCCAACG57466-01 DNA SequenceATGGACAGCTGGTGAACCCCAACAACTTCTGGAAGAACCCGAAAGATGTGTGCGCCCACGCCCATGGCCTCTCAGGGCCCAGGCCTGGGACGTGACCACCACTAACTGCTCAGCCAATATCAACTTGACCCACCAGCCCTGGTTCCAGGTCCTGGAGCCGCAGTTCCGGCAGTTTCTCTTCTACCGCCACTGCCGCTACTTCCCCATGCTGCTGAACCACCCGGAGAAGTGCAGGGGCGATGTCTACCTGCTGGTGGTTGTCAAGTCGGTCATCACGCAGCACGACCGCCGCGAGGCCATCCGCCAGACCTGGGCGCGAGCGGCAGTCCGCGGGTGGGGGCCGAGCGCCGTGCGCACCCTCTTCCTGCTGGGCACGGCCTCCAAGCAGGAGGAGCGCACGCACTACCAGCAGCTGCTGGCCTACGAAGACGCCCTCTACGGCGACATCCTGCAGTGGGGCTTTCTCGACACCTTCTTCAACCTGACCCTCAAGGAGATCCACTTCCTCAAGTGGCTGGACATCTACTGCCCCCACGTCCCCTTCATTTTCAAAGGCGACGATGACGTCTTCGTCAACCCCACCAACCTGCTAGAATTTCTGGCTGACCGGCAGCCACAGGAAAACCTGTTCGTGGGCGATGTCCTGCAGCACGCTCGGCCCATTCGCAGGAAAGACAACAAATACTACATCCCGGGGGCCCTGTACGGCAAGGCCAGCTATCCGCCGTATGCAGGCGGCGGTGGCTTCCTCATGGCCGGCAGCCTGGCCCGGCGCCTGCACCATGCCTGCGACACCCTGGAGCTCTACCCGATCGACGACGTCTTTCTGGGCATGTGCCTGGAGGTGCTGGGCGTGCAGCCCACGGCCCACGAGGGCTTCAAGACTTTCGGCATCTCCCGGAACCGCAACAGCCGCATGAACAAGGAGCCGTGCTTTTTCCGCGCCATGCTCGTGGTGCACAAGCTGCTGCCCCCTGAGCTGCTCGCCATGTGGGGGCTGGTGCACAGCAATCTCACCTGCTCCCGCAAGCTCCAGGTGCTCTGACCCCAGCCGGGCTACTAGGACAGGCCAGGGCACORF Start: ATG at 9ORF Stop: TGA at 1101SEQ ID NO:302364 aaMW at 41853.8 kDNOV106a,MGASATHPGATEGPEAKWTAGEPQQLLEEPERCVRPRPWPLRAQAWDVTTTNCSANINCG57466-01 Protein SequenceLTHQPWFQVLEPQFRQFLFYRHCRYFPDMLLNHPEKCRGDVYLLVVVKSVITQHDRREAIRQTWARAAVRGWGPSAVRTLFLLGTASKQEERTHYQQLLAYEDALYGDILQWGFLDTFFNLTLKEIHFLKWLDIYCPHVPFIFKGDDDVFVNPTNLLEFLADRQPQENLFVGDVLQHARPIRRKDNKYYIPGALYGKASYPPYAGGGGFLMAGSLARRLHHACDTLELYPIDDVFLGMCLEVLGVQPTAHEGFKTFGISRNRNSRMNKEPCFFRAMLVVHKLLPPELLAMWGLVHSNLTCSRKLQVL


[0880] Further analysis of the NOV106a protein yielded the following properties shown in Table 106B.
556TABLE 106BProtein Sequence Properties NOV106aPSort0.6400 probability located in microbody (peroxisome); 0.4500analysis:probability located in cytoplasm; 0.3122 probability locatedin lysosome (lumen); 0.1000 probability located inmitochondrial matrix spaceSignalPNo Known Signal Sequence Predictedanalysis:


[0881] A search of the NOV106a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 106C.
557TABLE 106CGeneseq Results for NOV106aNOV106aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAB24035Human PRO4397 protein sequence72 . . . 352149/300 (49%)4e−76SEQ ID NO: 42-Homo sapiens,84 . . . 380191/300 (63%)402 aa. [WO200053750-A1,14 SEP. 2000]AAU29167Human PRO polypeptide sequence26 . . . 363149/348 (42%)9e−76#144-Homo sapiens, 372 aa.27 . . . 371207/348 (58%)[WO200168848-A2,20 SEP. 2001]AAB88404Human membrane or secretory26 . . . 363149/348 (42%)9e−76protein clone PSEC0159-Homo27 . . . 371207/348 (58%)sapiens, 372 aa. [EP1067182-A2,10 JAN. 2001]AAB49750Human beta 1,3-N-26 . . . 363149/348 (42%)9e−76acetylglucosamine transferase27 . . . 371207/348 (58%)protein G4-Homo sapiens, 372 aa.[WO200100848-A1, 4 JAN. 2001]AAB49749Human beta 1,3-N-26 . . . 363149/348 (42%)9e−76acetylglucosamine transferase27 . . . 371207/348 (58%)protein G4-Homo sapiens, 372 aa.[WO200100848-A1, 4 JAN. 2001]


[0882] In a BLAST search of public sequence databases, the NOV106a protein was found to have homology to the proteins shown in the BLASTP data in Table 106D.
558TABLE 106DPublic BLASTP Results for NOV106aNOV106aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueAAL32295BETA-3-GALACTOSYLTRANSFERASE- 46 . . . 364199/319 (62%) e−121Brachydanio rerio (Zebrafish) (Zebra danjo),101 . . . 417249/319 (77%)418 aa.AAL32297BETA-3-GALACTOSYLTRANSFERASE- 29 . . . 360180/337 (53%) e−104Brachydanio rerio (Zebrafish) (Zebra danio), 82 . . . 409244/337 (71%)412 aa.Q96EK0UNKNOWN (PROTEIN FOR MGC: 20513)- 60 . . . 352152/313 (48%)9e−76Homo sapiens (Human), 377 aa. 46 . . . 355198/313 (62%)CAC39768SEQUENCE 175 FROM PATENT 26 . . . 363149/348 (42%)3e−75EP1067182-Homo sapiens (Human), 372 aa. 27 . . . 371207/348 (58%)Q9C0J2BETA-1,3-N- 26 . . . 363149/348 (42%)3e−75ACETYLGLUCOSAMINYLTRANSFERASE 27 . . . 371207/348 (58%)BGNT-3-Homo sapiens (Human), 372 aa.


[0883] PFam analysis predicts that the NOV106a protein contains the domains shown in the Table 106E.
559TABLE 106EDomain Analysis of NOV106aIdentities/PfamNOV106aSimilarities forExpectDomainMatch Regionthe Matched RegionValueP13_P14_kinase:195 . . . 205 8/12 (67%)8.5domain 1 of 1 10/12 (83%)Galactosyl_T:112 . . . 308 69/212 (33%)7.7e−45domain 1 of 1148/212 (70%)



Example 107

[0884] The NOV107 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 107A.
560TABLE 107ANOV107 Sequence AnalysisSEQ ID NO:3034091 bpNOV 107a,AAGCAAGAGGCTGAGATGGATCTTGAGGCGGCAAAGAACGGAACAGCCTGGCGCCCCACG57468-01 DNA SequenceCGAGCGCGGAGGGCGACTTTGAACTGGGCATCAGCAGCAAACAAAAAAGGAAAAAAACGAAGACAGTGAAAATGATTGGAGTATTAACATTGTTTCGATACTCCGATTGGCAGGATAAATTGTTTATGTCGCTGGGTACCATCATGGCCATAGCTCACGGATCAGGTCTCCCCCTCATGATGATAGTATTTGGAGAGATGACTGACAAATTTGTTGATACTGCAGGAAACTTCTCCTTTCCAGTGAACTTTTCCTTGTCGCTGCTAAATCCAGGCAAAATTCTGGAAGAAGAAATGACTAGATATGCATATTACTACTCAGGATTGGGTGCTGGAGTTCTTGTTGCTGCCTATATACAAGTTTCATTTTGGACTTTGGCAGCTGGTCGACAGATCAGGAAAATTAGGCAGAAGTTTTTTCATGCTATTCTACGACAGGAAATAGGATGGTTTGACATCAATGACACCACTGAACTCAATACGCGGCTAACAGATGACATCTCCAAAATCAGTGAAGGAATTGGTGACAAGGTTGGAATGTTCTTTCAAGCAGTAGCCACGTTTTTTGCAGGATTCATAGTGGGATTCATCAGAGGATGGAAGCTCACCCTTGTGATAATGGCCATCAGCCCTATTCTAGGACTCTCTGCAGCCGTTTGGGCAAAGATACTCTCGGCATTTAGTGACAAAGAACTAGCTGCTTATGCAAAAGCAGGCGCCGTGGCAGAAGAGGCTCTGGGGGCCATCAGGACTGTGATAGCTTTCGGGGGCCAGAACAAAGAGCTGGAAAGGTATCAGAAACATTTAGAAAATGCCAAAGAGATTGGAATTAAAAAAGCTATTTCAGCAAACATTTCCATGGGTATTGCCTTCCTGTTAATATATGCATCATATGCACTGGCCTTCTGGTATGGATCCACTCTAGTCATATCAAAAGAATATACTATTGGAAATGCAATGACAGTTTTTTTTTCAATCCTAATTGGAGCTATGGCCATCGGAGAAACGCTCGTTTTGGCTCCTGAATATTCCAAAGCCAAATCGGGGGCTGCGCATCTGTTTGCCTTGTTGGAAAAGAAACCAAATATAGACAGCCGCAGTCAAGAAGGGAAAAAGCCAGTAAGCGACACATGTGAAGGGAATTTAGAGTTTCGAGAAGTCTCTTTCTTCTATCCATGTCGCCCAGATGTTTTCATCCTCCGTGGCTTATCCCTCAGTATTGAGCGAGGAAAGACAGTAGCATTTGTGGGGAGCAGCGGCTGTGGGAAAAGCACTTCTGTTCAACTTCTGCAGAGACTTTATGACCCCGTGCAAGGACAAGTGGATGGTGTGGATGCAAAAGAATTGAATGTACAGTGGCTCCGTTCCCAAATAGCAATCGTTCCTCAAGAGCCTGTGCTCTTCAACTGCAGCATTGCTGAGAACATCGCCTATGGTGACAACAGCCGTGTGGTGCCATTAGATGAGATCAAAGAAGCCGCAAATGCAGCAAATATCCATTCTTTTATTGAAGGTCTCCCTGAGAAATACAACACACAAGTTGGACTGAAAGGAGCACAGCTTTCTGGCGGCCAGAAACAAAGACTAGCTATTGCAAGGGCTCTTCTCCAAAAACCCAAAATTTTATTGTTGGATGAGGCCACTTCAGCCCTCGATAATGACAGTGAGTGGCAGGTGGTTCAGCATGCCCTTGATAAAGCCAGGACGGGAAGGACATGCCTAGTGGTCACTCACAGGCTCTCTGCAATTCAGAACGCAGATTTGATAGTGGTTCTGCACAATGGAAAGATAAAGGAACAAGGAACTCATCAAGAGCTCCTGAGAAATCGAGACATATATTTTAAGTTAGTGAATGCACAGTCAGCGAGCAAAGGTCGGACTACAATCGTGGTAGCACACCGACTTTCTACTATTCGAAGTGCAGATTTGATTGTGACCCTAAAGGATGGAATGCTGGCGGAGAAAGGAGCACATGCTGAACTAATGGCAAAACGAGGTCTATATTATTCACTTGTGATGTCACAGGTAATGCTTATGGGGACTCTTTCAGACTGTGGTAATAGTCTTCCTGAAGTCTCTCTATTAAAAATTTTAAAGTTAAACAAGCCTGAATGGCCTTTTGTGGTTCTGGGGACATTGGCTTCTGTTCTAAATGGAACTGTTCATCCAGTATTTTCCATCATCTTTGCAAAAATTATAACCGTAATGTTTGGAAATAATGATCTTTTGTTTTTCCTCAAAATTTTTTTATATTCATTCCTTTTGTTTTTCCTCAAACAAGGTTTCAGCGTAGATTTTTGTTTGTTTGCTTTTCAGGGATTATTTTACGGCAGAGCAGGGGAAATTTTAACGATGAGATTAAGACACTTGGCCTTCAAAGCCATGTTATATCAGGATATTGCCTGGTTTGATGAAAAGGAAAACAGCACAGGAGGCTTGACAACAATATTAGCCATAGATATAGCACAAATTCAAGGAGCAACAGGTTCCAGGATTGGCGTCTTAACACAAAATGCAACTAACATGGGACTTTCAGTTATCATTTCCTTTATATATGGATGGGAGATGACATTCCTGATTCTGAGTATTGCTCCAGTACTTGCCGTGACAGGAATGATTGAAACCGCAGCAATGACTGGATTTGCCAACAAAGATAAGCAAGAACTTAAGCATGCTGGAAAGGTAAAGATAGCAACTGAAGCTTTGGAGAATATACGTACTATAGTGTCATTAACAAGGGAAAAAGCCTTCGAGCAAATGTATGAAGAGATGCTTCAGACTCAACACAGGAGAAATACCTCGAAGAAAGCACAGATTATTGGAAGCTGTTATGCATTCAGCCATGCCTTTATATATTTTGCCTATGCGGCAGGGTTTCGATTTGGAGCCTATTTAATTCAAGCTGGACGAATGTCAAATGCTTTATCTTTTGATAGAGTTTTTACTGCAATTGCATATGGAGCTATGGCCATCGGAGAAACGCTCGTTTTGGCTCCTGAATATTCCAAAGCCAAATCGGGGGCTGCGCATCTGTTTGCCTTGTTGGAAAAGAAACCAAATATAGACAGCCGCAGTCAAGAAGGGAAAAAGCCACTTTCACAGGACACATGTGAAGGGAATTTAGAGTTTCGAGAAGTCTCTTTCTTCTATCCATGTCGCCCAGATGTTTTCATCCTCCGTGGCTTATCCCTCAGTATTGAGCGAGGAAAGACAGTAGCATTTGTGGGGAGCAGCGGCTGTGGGAAAAGCACTTCTGTTCAACTTCTGCAGAGACTTTATGACCCCGTGCAAGGACAACAGCTGTTTGATGGTGTGGATGCAAAAGAATTGAATGTACAGTGGCTCCGTTCCCAAATAGCAATCGTTCCTCAAGAGCCTGTGCTCTTCAACTGCAGCATTGCTGAGAACATCGCCTATGGTGACAACAGCCGTGTGGTGCCATTAGATGAGATCAAAGAAGCCGCAAATGCAGCAAATATCCATTCTTTTATTGAAGGTCTCCCTAAATACAACACACAAGTTGGACTGAAAGGAGCACAGCTTTCTGGCGGCCAGAAACAAAGACTAGCTATTGCAAGGGCTCTTCTCCAAAAACCCAAAATTTTATTGTTGGATGAGGCCACTTCAGCCCTCGATAATGACAGTGAGAAGGTACAGGTGGTTCAGCATGCCCTTGATAAAGCCAGGACGGGAAGGACATGCCTAGTGGTCACTCACAGGCTCTCTGCAATTCAGAACGCAGATTTGATAGTGGTTCTGCACAATGGAAAGATAAAGGAACAAGGAACTCATCAAGAGCTCCTGAGAAATCGAGACATATATTTTAAGTTAGTGAATGCACAGTCAGCGAGCAAAGGTCGGACTACAATCGTGGTAGCACACCGACTTTCTACTATTCGAAGTGCAGATTTGATTGTGACCCTAAAGGATGGAATGCTGGCGGAGAAAGGAGCACATGCTGAACTAATGGCAAAACGAGGTCTATATTATTCACTTGTGATGTCACAGGTAATGCTTATGTGACATAATGCTATORF Start: ATG at 16ORF Stop: TGA at 4078SEQ ID NO:3041354 aaMW at 149167.3 kDNOV107a,MDLEAAKNGTAWRPTSAEGDFELGISSKQKRKKTKTVKMIGVLTLFRYSDWQDKLFMSCG57468-01 ProteinSequenceLGTIMAIAHGSGLPLMMIVFGEMTDKFVDTAGNFSFPVNFSLSLLNPGKILEEEMTRYAYYYSGLGAGVLVAAYIQVSFWTLAAGRQIRKIRQKFFHAILRQEIGWFDINDTTELNTRLTDDISKISEGIGDKVGMFFQAVATFFAGFIVGFIRGWKLTLVIMAISPILGLSAAVWAKILSAFSDKELAAYAKAGAVAEEALGAIRTVIAFGGQNKELERYQKHLENAKEIGIKKAISANISMGIAFLLIYASYALAFWYGSTLVISKEYTIGNAMTVFFSILIGAMAIGETLVLAPEYSKAKSGAAHLFALLEKKPNIDSRSQEGKKPVSDTCEGNLEFREVSFFYPCRPDVFILRGLSLSIERGKTVAFVGSSGCGKSTSVQLLQRLYDPVQGQVDGVDAKELNVQWLRSQIAIVPQEPVLFNCSIAENIAYGDNSRVVPLDEIKEAANAANIHSFIEGLPEKYNTQVGLKGAQLSGGQKQRLAIARALLQKPKILLLDEATSALDNDSEWQVVQHALDKARTGRTCLVVTHRLSAIQNADLIVVLHNGKIKEQGTHQELLRNRDIYFKLVNAQSASKGRTTIVVAHRLSTIRSADLIVTLKDGMLAEKGAHAELMAKRGLYYSLVMSQVMLMGTLSDCGNSLPEVSLLKILKLNKPEWPFVVLGTLASVLNGTVHPVFSIIFAKIITVMFGNNDLLFFLKIFLYSFLLFFLKQGFSVDFCLFAFQGLFYGRAGEILTMRLRHLAFKAMLYQDIAWFDEKENSTGGLTTILAIDIAQIQGATGSRIGVLTQNATNMGLSVIISFIYGWEMTFLILSIAPVLAVTGMIETAAMTGFANKDKQELKHAGKVKIATEALENIRTIVSLTREKAFEQMYEEMLQTQHRRNTSKKAQIIGSCYAFSHAFIYFAYAAGFRFGAYLIQAGRMSNALSFDRVFTAIAYGAMAIGETLVLAPEYSKAKSGAAHLFALLEKKPNIDSRSQEGKKPLSQDTCEGNLEFREVSFFYPCRPDVFILRGLSLSIERGKTVAFVGSSGCGKSTSVQLLQRLYDPVQGQQLFDGVDAKELNVQWLRSQIAIVPQEPVLFNCSIAENIAYGDNSRVVPLDEIKEAANAANIHSFIEGLPKYNTQVGLKGAQLSGGQKQRLAIARALLQKPKILLLDEATSALDNDSEKVQVVQHALDKARTGRTCLVVTHRLSAIQNADLIVVLHNGKIKEQGTHQELLRNRDIYFKLVNAQSASKGRTTIVVAHRLSTIRSADLIVTLKDGMLAEKGAHAELMAKRGLYYSLVMSQVMLM


[0885] Further analysis of the NOV107a protein yielded the following properties shown in Table 107B.
561TABLE 107BProtein Sequence Properties NOV107aPSort0.6000 probability located in plasma membrane; 0.4000analysis:probability located in Golgi body; 0.3000 probabilitylocated in endoplasmic reticulum (membrane); 0.3000probability located in microbody (peroxisome)SignalPNo Known Signal Sequence Predictedanalysis.


[0886] A search of the NOV107a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 107C.
562TABLE 107CGeneseq Results for NOV107aNOV107aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAB81064Cynomologous monkey P-1 . . . 1299750/1312 (57%)0.0glycoprotein variant 1-Macaca1 . . . 1278964/1312 (73%)fascicularis, 1280 aa.[WO200123565-A1, 5 APR. 2001]AAB81065Cynomologous monkey P-1 . . . 1299749/1312 (57%)0.0glycoprotein variant 2-Macaca1 . . . 1281967/1312 (73%)fascicularis, 1283 aa.[WO200123565-A1, 5 APR. 2001]AAB81959Human MDR1-Homo sapiens,1 . . . 1299749/1324 (56%)0.01280 aa. [WO200121762-A2,1 . . . 1278967/1324 (72%)29 MAR. 2001]AAY58186Human wild-type multidrug1 . . . 1299749/1324 (56%)0.0resistance-1 (MDR-1) protein-1 . . . 1278967/1324 (72%)Homo sapiens, 1280 aa.[WO9961589-A2, 2 DEC. 1999]AAW44073Human multidrug resistance P-1 . . . 1299749/1324 (56%)0.0glycoprotein MDR1-Homo1 . . . 1278967/1324 (72%)sapiens, 1280 aa. [WO9740160-A1, 30 OCT. 1997]


[0887] In a BLAST search of public sequence databases, the NOV107a protein was found to have homology to the proteins shown in the BLASTP data in Table 107D.
563TABLE 107DPublic BLASTP Results for NOV107aNOV107aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueP23174Multidrug resistance protein 3 (P-1 . . . 1299818/1303 (62%)0.0glycoprotein 3)-Cricetulus1 . . . 1279999/1303 (75%)griseus (Chinese hamster), 1281aa.P21440Multidrug resistance protein 2 (P-1 . . . 1299823/1306 (63%)0.0glycoprotein 2)-Mus musculus1 . . . 1274998/1306 (76%)(Mouse), 1276 aa.Q08201Multidrug resistance protein 2 (P-1 . . . 1299823/1309 (62%)0.0glycoprotein 2)-Rattus1 . . . 1276999/1309 (75%)norvegicus (Rat), 1278 aa.CAC37764SEQUENCE 1 FROM PATENT1 . . . 1299750/1312 (57%)0.0WO0123565-Macaca fascicularis1 . . . 1278964/1312 (73%)(Crab eating macaque)(Cynomolgus monkey), 1280 aa.CAC37765SEQUENCE 3 FROM PATENT1 . . . 1299749/1312 (57%)0.0WO0123565-Macaca fascicularis1 . . . 1281967/1312 (73%)(Crab eating macaque)(Cynomolgus monkey), 1283 aa.


[0888] PFam analysis predicts that the NOV107a protein contains the domains shown in the Table 107E.
564TABLE 107EDomain Analysis of NOV107aIdentities/PfamNOV107aSimilarities forExpectDomainMatch Regionthe Matched RegionValueABC_membrane: 57 . . . 350115/301 (38%)3.3e−83domain 1 of 2252/301 (84%)MVIN: 57 . . . 447 70/531 (13%)5.8domain 1 of 1263/531 (50%)SAA_proteins: 518 . . . 524 6/7 (86%)3domain 1 of 1 7/7 (100%)ABC_tran: 424 . . . 609 76/199 (38%)3.1e−56domain 1 of 2150/199 (75%)DsbD: 722 . . . 926 39/249 (16%)9.6domain 1 of 1126/249 (51%)ABC_membrane: 722 . . . 1008 80/297 (27%)2.2e−43domain 1 of 2222/297 (75%)ABC_tran:1083 . . . 1270 77/202 (38%)7.1e−54domain 2 of 2154/202 (76%)GidB:1170 . . . 1312 29/202 (14%)6.6domain 1 of 1 97/202 (48%)



Example 108

[0889] The NOV108 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 108A.
565TABLE 108ANOV108 Sequence AnalysisSEQ ID NO:305520 bpNOV 108a,CCCCGTTCTATCAGCCATGGTCAACCCCACCAGGTTCTTAGACATCATCGTGGATGGTCG59609-01 DNA SequenceGAGCTCTTGGGACGTGTCTCCTTTGAGCTGTTTGCAGACAAGATTCCAAAGACAGCAGAAAATTTTTGTGCTCTAATCATTGGAGAGAAAGGATTTGGTTATAAAGGTTCCTACTTTCACAGAATTGTTCCTGGGTTTATGTGTCAGGGTGGTGACTTCACACAGCATAATGGCACTGGTGGCAAGTCCATCTACGGGAAGAAATTTGATGATGAGAACTTCGTCCTAAATTATACAGGTCCTGGCATCTTGTCCGTGGAGAATGCTGGACCCAACACAAATGGTTCCCAGTTTTTCATCTGCACTGCCATGTCTGAGTGGTTGGATGGCATGCAGGTGGTCTTTGGCAAGGGAAGGAAGGTGAGTATTGTGGAAGCCATGGAGTGCTTTGGGTCCACAAATGGCAAGACCAGCAAGAAGATCACCATTGCTGACTGTGGACAACTCTAATAGGTTTGACTTORF Start: ATG at 17ORF Stop: TAA at 506SEQ ID NO:306163 aaMW at 17734.1 kDNOV 108a,MVNPTRFLDIIVDGELLGRVSFELFADKIPKTAENFCALIIGEKGFGYKGSYFHRIVPCG59609-01 Protein SequenceGFMCQGGDFTQHNGTGGKSIYGKKFDDENFVLNYTGPGILSVENAGPNTNGSQFFICTAMSEWLDCMQVVGKCRKVGIVEAMECFGSTNCKTSKKITIADCGQL


[0890] Further analysis of the NOV108a protein yielded the following properties shown in Table 108B.
566TABLE 108BProtein Sequence Properties NOV108aPSort0.6400 probability located in microbody (peroxisome);analysis:0.6000 probability located in plasma membrane; 0.4500probability located in cytoplasm; 0.1000 probabilitylocated in mitochondrial matrix spaceSignalPNo Known Signal Sequence Predictedanalysis:


[0891] A search of the NOV108a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 108C.
567TABLE 108CGeneseq Results for NOV108aNOV108aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAU01195Human cyclophilin A protein-1 . . . 163134/164 (81%)2e−75Homo sapiens, 165 aa.1 . . . 164147/164 (88%)[WO200132876-A2, 10 MAY 2001]AAW56028Calcineurin protein-Mammalia,1 . . . 163134/164 (81%)2e−75165 aa. [WO9808956-A2,1 . . . 164147/164 (88%)5 MAR 1998]AAR13726Bovine cyclophilin-Bos taurus,2 . . . 163133/163 (81%)5e−75163 aa. [U.S. Pat. No. 5047512-A,1 . . . 163146/163 (88%)10 SEP. 1991]AAG65275Haematopoietic stem cell2 . . . 163133/163 (81%)9e−75proliferation agent related human1 . . . 163146/163 (88%)protein #2-Homo sapiens, 164 aa.[JP2001163798-A, 19 JUN. 2001]AAP90431Cyclophilin-Homo sapiens2 . . . 163133/163 (81%)9e−75(human), 164 aa. [EP326067-A,1 . . . 163146/163 (88%)2 AUG. 1989]


[0892] In a BLAST search of public sequence databases, the NOV108a protein was found to have homology to the proteins shown in the BLASTP data in Table 108D.
568TABLE 108DPublic BLASTP Results for NOV108aNOV108aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueCAC39529SEQUENCE 26 FROM PATENT1 . . . 163134/164 (81%)8e−75WO0132876-Homo sapiens1 . . . 164147/164 (88%)(Human), 165 aa.Q9BRU4PEPTIDYLPROLYL ISOMERASE1 . . . 163134/164 (81%)2e−74A (CYCLOPHILIN A)-Homo1 . . . 164146/164 (88%)sapiens (Human), 165 aa.P04374Peptidyl-prolyl cis-trans isomerase2 . . . 163133/163 (81%)2e−74A (EC 5.2.1.8) (PPIase) (Rotamase)1 . . . 163146/163 (88%)(Cyclophilin A) (Cyclosporin A-binding protein)-Bos taurus(Bovine), and, 163 aa.P05092Peptidyl-prolyl cis-trans isomerase2 . . . 163133/163 (81%)3e−74A (EC 5.2.1.8) (PPIase) (Rotamase)1 . . . 163146/163 (88%)(Cyclophilin A) (Cyclosporin A-binding protein)-Homo sapiens(Human),, 164 aa.Q9TTC6CYCLOPHILIN 18-Oryctolagus1 . . . 163133/164 (81%)5e−74cuniculus (Rabbit), 164 aa.1 . . . 164147/164 (89%)


[0893] PFam analysis predicts that the NOV108a protein contains the domains shown in the Table 108E.
569TABLE 108EDomain Analysis of NOV108aIdentities/PfamNOV108aSimilarities forExpectDomainMatch Regionthe Matched RegionValuepro_isomerase:5 . . . 163101/181 (56%)5.2e−79domain 1 of 1137/181 (76%)



Example 109

[0894] The NOV109 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 109A.
570TABLE 109ANOV109 Sequence AnalysisSEQ ID NO:307887 bpNOV109a,GATATCATTTTTTATGGCAGCCATTGTTAAGCCTCCAGAACCTATACCTTTAAAATGGCG59613-01 DNA SequenceTTAACAGATAAGCCAGTTTGGATAGAACAATGGCCACTGAGTAAAGAGAAACTGGAGGCTTTAGAGGATTTGGTTACTGAACAATTCTCAATAATCATTTTCCAAAAAGTGAACCTACACAGCATGAAAGTATCACACATTTCCTTAGTGCAGCTAACCCTGTGTGACCAGGGCTTCAACACATACCACTGTGACCACAACCTAGCCATGAGCATGAGCCTCACCAGCATGTCCAAAATGCTAAAATACAACAATGGCAGTGAAGACATCACTACATGGAGGGCTGAAGGTACTATGGATCTCTTGGTGCTAGAATTTGAAGCACTAAATCAAGAGAACTTTGTGGACTGTGAATTGAAGTTAATGACTCTAGATGTTGAGCAACTTGAAATTCCAGAACAAGAGTACAGCTGTGTAATAAAGATGCATTCTAGTGAATTTGTTCATATATGCCAAGATCTCAGTCATATTGGAGAGTCTGCTATAATTTCTTGTGCAAAAGATGGAGTGAATTTTTCTGCAAATGGAGAACTTGGACATGGAAACATTGCCACAATTGCCCAAACAAGTAATTACAATAAAGAAGAGGAGGCTGTTGCCATAATGATGAATGGGCCAGTTCAGCTAACTTTTGCACTAAGTTACTTAAATTTCTTTATAACAGGCACTCCACTCTCTCAGATGCACCCCTTGCTGGAGAGTATAAGATTGCCGGATATGGAACATTTAAAGTATTATTTGGCTCCCAAAATTGAGGATGAAAAAGGATTTTAGAAATTCTTAGAATCCAAGAAAATAAAACTAAGCTCTTTGAAAATTGCTTCTGAGAORF Start: ATG at 14ORF Stop: TAG at 830SEQ ID NO:308272 aaMW at 30831.1 kDNOV109a,MAAIVKPPEPIPLKWLTDKPVWIEQWPLSKEKLEALEDLVTEQFSIIIFQKVNLHSMKCG59613-01 Protein SequenceVSHISLVQLTLCDQGFNTYHCDHNLAMSMSLTSMSKMLKYNNGSEDITTWRAEGTMDLLVLEFEALNQENFVDCELKLMTLDVEQLEIPEQEYSCVIKMHSSEFVHICQDLSHIGESAIISCAKDGVNFSANGELGHGNIATIAQTSNYNKEEEAVAIMMNGPVQLTFALSYLNFFITGTPLSQMHIPLLESIRLPDMEHLKYYLAPKIEDEKGF


[0895] Further analysis of the NOV109a protein yielded the following properties shown in Table 109B.
571TABLE 109BProtein Sequence Properties NOV109aPSort0.6500 probability located in cytoplasm; 0.1000 probabilityanalysis:located in mitochondrial matrix space; 0.1000 probabilitylocated in lysosome (lumen); 0.0000 probability located inendoplasmic reticulum (membrane)SignalPLikely cleavage site between residues 19 and 20analysis:


[0896] A search of the NOV109a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 109C.
572TABLE 109CGeneseq Results for NOV109aNOV109aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAY51639Human PCNA protein fragment-25 . . . 271158/255 (61%)8e−78Homo sapiens, 261 aa. 8 . . . 260184/255 (71%)[WO200008164-A2, 17 FEB. 2000]AAY52010Human PCNA protein-Homo25 . . . 271158/255 (61%)8e−78sapiens, 261 aa. [DE19840771-A1, 8 . . . 260184/255 (71%)10 FEB. 2000]AAB43712Human cancer associated protein25 . . . 271158/255 (61%)8e−78sequence SEQ ID NO: 1157-Homo16 . . . 268184/255 (71%)sapiens, 269 aa. [WO200055350-A1, 21 SEP. 2000]AAG75139Human colon cancer antigen25 . . . 269157/253 (62%)5e−77protein SEQ ID NO: 5903-Homo16 . . . 266182/253 (71%)sapiens, 268 aa. [WO200122920-A2, 5 APR. 2001]AAW90758Human PCNA protein fragment #2-39 . . . 268149/238 (62%)7e−73Homo sapiens, 236 aa. 1 . . . 236171/238 (71%)[DE19840771-A1, 10 FEB. 2000]


[0897] In a BLAST search of public sequence databases, the NOV109a protein was found to have homology to the proteins shown in the BLASTP data in Table 109D.
573TABLE 109DPublic BLASTP Results for NOV109aNOV109aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueP12004Proliferating cell nuclear antigen25 . . . 271158/255 (61%)3e−77(PCNA) (Cyclin)-Homo sapiens 8 . . . 260184/255 (71%)(Human), 261 aa.P04961Proliferating cell nuclear antigen25 . . . 271158/255 (61%)5e−77(PCNA) (Cyclin)-Rattus norvegicus 8 . . . 260185/255 (71%)(Rat), 261 aa.P57761Proliferating cell nuclear antigen25 . . . 271158/255 (61%)7e−77(PCNA)-Cricetulus griseus 8 . . . 260184/255 (71%)(Chinese hamster), 261 aa.Q91ZH211 DAYS EMBRYO CDNA,25 . . . 272156/256 (60%)1e−75RIKEN FULL-LENGTH 8 . . . 261183/256 (70%)ENRICHED LIBRARY,CLONE: 2700095L20, FULLINSERT SEQUENCE-Musmusculus (Mouse), 261 aa.P17918Proliferating cell nuclear antigen25 . . . 270155/254 (61%)5e−75(PCNA) (Cyclin)-Mus musculus 8 . . . 259182/254 (71%)(Mouse), 261 aa.


[0898] PFam analysis predicts that the NOV109a protein contains the domains shown in the Table 109E.
574TABLE 109EDomain Analysis of NOV109aIdentities/PfamNOV109aSimilarities forExpectDomainMatch Regionthe Matched RegionValuePCNA: 23 . . . 14346/128 (36%)2.3e−20domain 1 of 183/128 (65%)PCNA_C:145 . . . 26559/131 (45%)1.6e−45domain 1 of 198/131 (75%)



Example 110

[0899] The NOV110 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 110A.
575TABLE 110ANOV110 Sequence AnalysisSEQ ID NO:3091233 bpNOV110a,TGGCAATGGAAGAAGAGATCCCCGCGCTCTTCATTGACAATGGCTCCGGCATGTGGAACG59619-01 DNA SequenceAGCAGCTTTGCTGGGAGACAATGCCCTCCGAGCCATATTCCCCTCCATCATCGGGCACCCCCGGCACCAGGGCGTGATGGTGGGCATGGGCCAGAAGGACTCCTACGTGGGCGACCAGGCCCAGAGCAAGTGCGGCATCCTGACCCTGAAGTACCCCATCAAGCATGGCATCGTCACAAACTGGGACGACATGGAGAAGATCTGGCACCATGTTTTCTACAACGAGCTGTGCGTGGCCCTGGAGGAGCAGGTGGTGCTGCTGACCGAGGCCCCGCTAAACCCCAGGGCCAATAGGGAGAAGATGACTCAGATCATGTTTAAGACCTTCAACACCCAGGCCATGTACGTGGCCATTCAGGCCGTGCTGACCCTCCACAGCTCTGGTTGCACCACTGGCATTGTCATGGACTCTGGAGATGGGGTCACCCACACAGTGCCCATCTACGAGCGCCACACCCTCCCTCACACCATCTTGCATCTGGACCTGGCTGGCCAGGACCTTACTGACTACCTCATGAAGATCCCTACCTACCGCAGCTATAGCTTCAACACCATGGCCAAGTGGAAAATCGTGCGCAACATCAAGGAGAAGCTATGCTATGTCGCTCTGGACTTCGAGGAGGAGATGGCCACTGCTGCATCCTCCTCCTCCCTGGAGAAGAGCTACGAGCTGCCTGACAGCCAGGCCATCATTATTAGCAATGAGCGGTTCCGGTGTCCGGAGGCACTGTTCCAGCCTTCCTTCCTGGGCATGGAATCCTGTGGCATCCATGAAAGTACCTTCAACTCCATCATGAAGTGTGATATGGACATCCCCAAAGACCTGTACGCCAACACAGTGCTGTCTGGCGTCACCACCATGTACCCTGGCATCCCCAATAGGATGCAGAAGGAGATCACTGCCCTGGCATCCAGCACCATGAAGATCAAGATATCGTGCCCCATCGTGCCCCCAGAGTGCAAGTACTTTGTGTGGATCGGTGGCTCCATCCTGGCCTCACTGTCCACCTTCCAGCAGATGTGGATTAGCAAGCAGGAGTACAACGAGTCGGGCCCCTCCATCATCCACCGCAAATGGACTGCGAGCAGATGCATAGCATTTGCTGCATGGGTTAATTCAGAAGTATAAATTTGCCCCTGGCAAATGCATATACCTCATGCTAGCCTCACGATACORF Start: ATG at 6ORF Stop: TAA at 1185SEQ ID NO:310393 aaMW at 44147.5 kDNOV110A,MEEEIPALFIDNGSGMWKAALLGDNALRAIFPSIIGHPRHQGVMVGMGQKDSYVGDQACG59619-01 Protein SequenceQSKCGILTLKYPIKHGIVTNWDDMEKIWHHVFYNELCVALEEQVVLLTEAPLNPRANREKMTQIMFKTFNTQAMYVAIQAVLTLHSSGCTTGIVMDSGDGVTHTVPIYERHTLPHTILHLDLAGQDLTDYLMKIPTYRSYSFNTMAKWKIVRNIKEKLCYVALDFEEEMATAASSSSLEKSYELPDSQAIIISNERFRCPEALFQPSFLGMESCGIHESTFNSIMKCDMDIPKDLYANTVLSGVTTMYPGIPNRMQKEITALASSTMKIKISCPIVPPECKYFVWIGGSILASLSTFQQMWISKQEYNESGPSIIHRKWTASRCTAFAAWVNSEV


[0900] Further analysis of the NOV110a protein yielded the following properties shown in Table 110B.
576TABLE 110BProtein Sequence Properties NOV110aPSort0.4500 probability located in cytoplasm; 0.1547 probabilityanalysis:located in microbody (peroxisome); 0.1000 probability locatedin mitochondrial matrix space; 0.1000 probability located inlysosome (lumen)SignalPNo Known Signal Sequence Predictedanalysis:


[0901] A search of the NOV110a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 110C.
577TABLE 110CGeneseq Results for NOV110aNOV110AIdentities/Residues/Similarities forGeneseqProtein/Organism/Length [PatentMatchthe MatchedExpectIdentifier+190, Date]ResiduesRegionValueAAU32060Novel human secreted protein1..3764 315/376 (83%)e−180#2551 - Homo sapiens, 399 aa.25..397 336/376 (88%)[WO200179449-A2, 25 OCT. 2001]AAB43991Human cancer associated protein1..376311/376 (82%)e−179sequence SEQ ID NO:1436 - Homo.39..411 336/376 (88%)sapiens, 413 aa. [WO200055350-A1, 21 SEP. 2000]AAP61532Sequence of beta-actin - Homo1..376311/376 (82%)e−179sapiens, 375 aa. [EP174608-A, 191..373335/376 (88%)MAR. 1986]AAB12985Human beta-actin protein sequence2..376310/375 (82%)e−178- Homo sapiens, 374 aa.1..372334/375 (88%)[US6087398-A, 11 JUL. 2000]AAR50328Drug resistant structural protein -1..376309/376 (82%)e−178Homo sapiens, 375 aa.1..373335/376 (88%)[JP06038773-A, 15 FEB. 1994]


[0902] In a BLAST search of public sequence databases, the NOV110a protein was found to have homology to the proteins shown in the BLASTP data in Table 110D.
578TABLE 110DPublic BLASTP Results for NOV110aNOV110aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueP02571Actin, cytoplasmic 2 (Gamma-actin)-1 . . . 376315/376 (83%)e−179Homo sapiens (Human),, 375 aa.1 . . . 373336/376 (88%)ATBOGactin gamma (tentative sequence)-2 . . . 376314/375 (83%)e−179bovine, 374 aa.1 . . . 372335/375 (88%)P53505Actin, cytoplasmic type 5-Xenopus2 . . . 376313/375 (83%)e−178laevis (African clawed frog), 376 aa.3 . . . 374335/375 (88%)P29751Actin, cytoplasmic 1 (Beta-actin)-1 . . . 376311/376 (82%)e−178Oryctolagus cuniculus (Rabbit), 3751 . . . 373337/376 (88%)aa.O93400ACTIN, CYTOPLASMIC 11 . . . 376311/376 (82%)e−178(BETA-ACTIN) (CYTOPLASMIC1 . . . 373336/376 (88%)BETA ACTIN)-Xenopus laevis(African clawed frog), 375 aa.


[0903] PFam analysis predicts that the NOV110a protein contains the domains shown in the Table 110E.
579TABLE 110EDomain Analysis of NOV110aIdentities/SimilaritiesNOV110afor theExpectPfam DomainMatch RegionMatched RegionValueactin: domain 1 of 11 . . . 378284/382 (74%)2.2e−227336/382 (88%)



Example 111.

[0904] The NOV111 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 111A.
580TABLE 111ANOV111 Sequence AnalysisSEQ ID NO:3111197 bpNOV111a,AACCATGTCTAAGCGGGAGTCCTTTAACCTGGAAAGTTATGAATTGGACAAAAGCTTCCG59621-01 DNA SequenceTGGCTAACCAGATTCACTGAACTGAAGGGCACAGGTTGCAAAGTGCCCCAAGATGTCTTGCAAAAATTGCTGGAATCTTTACAGGAGAACCACTTCCAAGAAGATGAGCAGTTTCTGGGAGCCGTTATGCCAAGGCTTCGCATTGGAATGGATACTTGTGCCATTTCTTTGAGGCATGGTGGGCTTTCCTTGGTTCAAACCACAGATTACATTTACCCGATCGTAGACGACCCTTACATGATGGGCAGGATAGCATGTGCCAATGTCCTCAGTGACCTCTATGCAATGGGGGTCACAGAATGTGACAATATGCTGATGCTCCTTGGAGTCAGTAATAAAATGACCGACAGGGAAAGGGATAAAGTGATGCCTCTGATTATCCAAAGTTTTAAAGATGCAGCTGAGGAAGCAGGAATGTCTGTAATGGTCAGCCAAACAGTACTAAATCCCTGGATTGTCCTGGGAGGAGTCACTACCACTGTCTTCCAGCCCAATGAATTTATCATGCCAGACAATGCAGTGCCAGGGGACGTGCTGGTGTTGACAAAACCCCTGGGGACACAGGTGGCAGTGGCTGTGCACCAGTGGCTGGATATTCCTTTGAAATGGAATAAGATTAAGCTAGTGGTCACCGAAGATGTAGAGCTGGCCAACCAGGAGGCGATGATGAACATGGTGAGGCTCAACAGGACAGCTGCAGGACTCATGCACACGTTCAATGCCCACATGGCCACTGACATCACGGGCTTCGGGATTTTGGGCCACGTGCAGAACCTAGCCAAGCAGCAGAGGAACGAGGTGTCGTTTGTAATTCACAACCTCCTGGTGCTGGCCAAGATGGCTGCGGTGAGCAAGGCCTGCGGAAACATGTTCAGCCTCATGCATGGGACCTGCCCGGAGACCTCAGGCGGCCTTCTGATCTGTTTACCATGTCAGCAAGCAGCTCGGTTCTGTGCAGAGATAAAGTCCCCCAAATATAGTGAAGGCCACCAAGCATGGATTATTGGGATTGTAGAGAAGGGCAACCACACAGCCAGAATCATAGACAAACCCCAGATCATCAAGGTTGCACCACAAGTGGCCACTCAAAATGTGAATCTCACACCCGGGGCCACATCTTAATCTAGACAGAAATAGCTORF Start: ATG at 5ORF Stop: TAA at 1178SEQ ID NO:312391 aaMW at 43193.9 kDNOV111a,MSKRESFNLESYELDKSFWLTRFTELKGTGCKVPQDVLQKLLESLQENHFQEDEQFLGCG59621-01 Protein SequenceAVMPRLRIGMDTCAISLRHGGLSLVQTTDYIYPIVDDPYMMGRIACANVLSDLYAMGVTECDNMLMLLGVSNKMTDRERDKVMPLIIQSFKDAAEEAGMSVMVSQTVLNPWIVLGGVTTTVFQPNEFIMPDNAVPGDVLVLTKPLGTQVAVAVHQWLDIPLKWNKIKLVVTEDVELANQEAMMNMVRLNRTAAGLMHTFNAHMATDITGFGILGHVQNLAKQQRNEVSFVIHNLLVLAKMAAVSKACGNMFSLMHGTCPETSGGLLICLPCQQAARFCAEIKSPKYSEGHQAWIIGIVEKGNHTARIIDKPQIIKVAPQVATQNVNLTPGATS


[0905] Further analysis of the NOV111a protein yielded the following properties shown in Table 111B.
581TABLE 111BProtein Sequence Properties NOV111aPSort0.8500 probability located in endoplasmic reticulumanalysis:(membrane); 0.4400 probability located in plasma membrane;0.1000 probability located in mitochondrial inner membrane;0.1000 probability located in Golgi bodySignalPNo Known Signal Sequence Predictedanalysis:


[0906] A search of the NOV111a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 111C.
582TABLE 111CGeneseq Results for NOV111aNOV111aIdentities/Residues/SimilaritiesGeneseqProtein/Organism/LengthMatchfor theExpectIdentifier[Patent #, Date]ResiduesMatched RegionValueAAB58174Lung cancer associated polypeptide166 . . . 391168/227(74%)2e−88sequence SEQ ID 512 - Homo 20 . . . 243189/227(83%)sapiens, 250 aa. [WO200055180-A2, 21 SEP 2000]AAO01161Human polypeptide SEQ ID NO147 . . . 26481/119(68%)2e−3615053 - Homo sapiens, 122 aa. 1 . . . 11892/119(77%)[WO200164835-A2, 7 SEP 2001]AAB53700Human colon cancer antigen protein42 . . . 9953/58(91%)1e−24sequence SEQ ID NO:1240 - Homo 1 . . . 5854/58(92%)sapiens, 106 aa. [WO200055351-A1, 21 SEP 2000]


[0907] In a BLAST search of public sequence databases, the NOV111a protein was found to have homology to the proteins shown in the BLASTP data in Table 111D.
583TABLE 111DPublic BLASTP Results for NOV111aNOV111aIdentities/ProteinResidues/SimilaritiesAccessionMatchfor theExpectNumberProtein/Organism/LengthResiduesMatched PortionValueQ9BVT4SELENOPHOSPHATE1 . . . 391364/392 (92%)0.0SYNTHETASE, HUMAN1 . . . 392367/392 (92%)SELENIUM DONOR PROTEIN -Homo sapiens (Human), 392 aa.P49903Selenide,water dikinase 1 (EC1 . . . 375348/376 (92%)0.02.7.9.3) (Selenophosphate1 . . . 376351/376 (92%)synthetase 1) (Selenium donorprotein 1) - Homo sapiens(Human), 383 aa.AAC50958SELENOPHOSPHATE2 . . . 391272/411 (66%)e−147SYNTHETASE 2- Homo sapiens33 . . . 441 313/411 (75%)(Human), 448 aa.Q99611Selenide,water dikinase 2 (EC2 . . . 391272/411 (66%)e−1472.7.9.3) (Selenophosphate33 . . . 441 313/411 (75%)synthetase 2) (Selenium donorprotein 2) - Homo sapiens(Human), 448 aa.AAC53024SELENOPHOSPHATE2 . . . 387267/407 (65%)e−146SYNTHETASE 2 - Mus musculus36 . . . 441 307/407 (74%)(Mouse), 452 aa.


[0908] PFam analysis predicts that the NOV111a protein contains the domains shown in the Table 111E.
584TABLE 111EDomain Analysis of NOV111aIdentities/SimilaritiesNOV111afor theExpectPfam DomainMatch RegionMatched RegionValueAIRS: domain 1 of 1 32 . . . 18829/180(16%)  3e−18113/180(63%)AIRS_C:191 . . . 36734/197(17%)1.1e−20domain 1 of 1125/197(63%)



Example 112.

[0909] The NOV112 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 112A.
585TABLE 112ANOV112 Sequence AnalysisSEQ ID NO:313544 bpNOV112a,CGATGGGACACAGACAGGTCACCCCAGCTCTGATCTTTGCCATCACAGTTGCTACAATCG59625-01 DNA SequenceCGGCTCTTTCCAGTTTGGCTACAACACTGGGGTCATCAATGCTCCTGAGACGGTGCAGATCATAAAGGAATTTATCAATAAAACTTTGACGGACAAGGCAAATGCCCCTCCCTCTGAGGTGCTGCTCACGAATCTCTGGTCCTTGTCTGTGGCCATATTTTCCGTCGGGGGTATGATCGGCTCCTTTTCCGTCGGACTCTTTGTTAACCGCTTTGGCAGGAGGCGCAATTCAATGCTGATTGTCAACCTGTTGGCTGCCACTGGTGGCTGCCTTATGGGACTGTGTAAAATAGCTGAGTCAGTTGAAATGCTGATCCTGGGCCGCTTGGTTATTGGCCTCTTCTGCGGACTCTGCACAGGTTTTGTGCCCATGTACATTGGAGAGATCTCGCCTACTGCCCTGAGGGGTGCCTTTGGCACTCTCAACCAGCTGGGCATAGTTATTGGAATTCTGGTGGCCCAGGTAATCTTTGGTCTGGAACTCATCCTTGGGTCTGAAGAGCTATGGCCGGTGCTATTAGGCTTTACCATCCTTCCAGCTATCCTGCAAAGTGCAGCCCTTCCATGTTGCCCTGAAAGTCCCAGATTTTTGCTCATTAACAGAAAAAAAGAGGAGAATGCTACGCGGGTCCTCCAGCGGTTGTGGGGCACCCAGGATGTATCCCAAGACATCCAGGAGATGAAAGATGAGAGTGCAAGGATGTCACAAGAAAAGCAAGTCACCGTGCTGGAGCTCTTTAGAGTGTCCAGCTACCGACAGCCCATCATCATTTCCATTGTGCTCCAGCTCTCTCAGCAGCTCTCTGGGATCAATGCTGTGGTGTTCTATTACTCAACAGGAATCTTCAAGGATGCAGGTGTTCAACAGCCCATCTATGCCACCATCAGCGCGGGTGTGGTTAATACTATCTTCACTTTACTTTCTGTAGTAGCTCAGATGCTGTTTTCATGGAAAGGAAAACTGAAGTTTCATGTCATAACTGTTTCTTTGTTATTAAAGCTGGGTTACACTGTCTTTAAATTTAATCTTCTGTGTTCCTTCCTCTTACAGAATCACTATAATGGGATGAGCTTTGTCTGTATTGGGGCTATCTTGGTCTTTGTGGCCTGTTTTGAAATTGGACCAGGCCCCATTCCCTGGTTTATTGTGGCCGAACTCTTCAGCCAGGGCCCCCGCCCAGCTGCGATGGCAGTGGCCGGCTGCTCCAACTGGACCTCCAACTTCCTAGTCGGATTGCTCTTCCCCTCTGCTGCTTACTATTTAGGAGCCTACGTTTTTATTATCTTCACCGGCTTCCTCATTACCTTCTTGGCCTTTACCTTCTTCAAAGTCCCTGAGACCCGTGGCAGGACTTTTGAGGATATCACACGGGCCTTTGAAGGGCAGGCACACGGTGCAGATAGATCTGGGAAGGACGGCGTCATGGGGATGAACAGCATCGAGCCTGCTAAGGAGACCACCACCAATGTCTAAGTCATGCCTCCTORF Start: ATG at 3ORF Stop: TAA at 1530SEQ ID NO:314509 aaMW at 55571.7 kDNOV112a,MGHRQVTPALIFAITVATIGSFQFGYNTGVINAPETVQIIKEFINKTLTDKANAPPSECG59625-01 Protein SequenceVLLTNLWSLSVAIFSVGGMIGSFSVGLFVNRFGRRRNSMLIVNLLAATGGCLMGLCKIAESVEMLILGRLVIGLFCGLCTGFVPMYIGEISPTALRGAFGTLNQLGIVIGILVAQVIFGLELILGSEELWPVLLGFTILPAILQSAALPCCPESPRFLLINRKKEENATRVLQRLWGTQDVSQDIQEMKDESARMSQEKQVTVLELFRVSSYRQPIIISIVLQLSQQLSGINAVVFYYSTGIFKDAGVQQPIYATISAGVVNTIFTLLSVVAQMLFSWKGKLKFHVITVSLLLKLGYTVFKFNLLCSFLLQNHYNGMSFVCIGAILVFVACFEIGPGPIPWFIVAELFSQGPRPAAMAVAGCSNWTSNFLVGLLFPSAAYYLGAYVFIIFTGFLITFLAFTFFKVPETRGRTFEDITRAFEGQAHGADRSGKDGVMGMNSIEPAKETTTNV


[0910] Further analysis of the NOV112a protein yielded the following properties shown in Table 112B.
586TABLE 112BProtein Sequence Properties NOV112aPsort0.6400 probability located in plasma membrane; 0.4600analysis:probability located in Golgi body; 0.3700 probabilitylocated in endoplasmic reticulum (membrane); 0.1000probability located in endoplasmic reticulum (lumen)SignalPLikely cleavage site between residues 22 and 23analysis:


[0911] A search of the NOV112a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 112C.
587TABLE 112CGeneseq Results for NOV112aNOV112aIdentities/Residues/SimilaritiesGeneseqProtein/Organism/LengthMatchfor theExpectIdentifier[Patent #, Date]ResiduesMatched RegionValueAAY27289Glucose transporter protein1 . . . 505389/505 (77%)0.0GLUT3 - Homo sapiens, 494 aa.1 . . . 492431/505 (85%)[US5942398-A, 24 AUG 1999]AAR11360Glucose Transporter Protein from4 . . . 491289/489 (59%)e−156CHO cells - Cricetulus sp, 492 aa.6 . . . 481364/489 (74%)[WO9103554-A, 21 MAR 1991]AAW17835Human glucose transporter GLUT-4 . . . 491287/489 (58%)e−1551 - Homo sapiens, 492 aa.6 . . . 481362/489 (73%)[WO9715668-A2, 1 MAY 1997]AAW93000Human GLUT1 protein - Homo4 . . . 491284/489 (58%)e−153sapiens, 492 aa. [WO9618957-A1,6 . . . 481360/489 (73%)20 JUN 1996]AAB30522Amino acid sequence of a6 . . . 501289/496 (58%)e−151consensus GLUT polypeptide -10 . . . 490 357/496 (71%)Synthetic, 493 aa. [US6136547-A,24 OCT 2000]


[0912] In a BLAST search of public sequence databases, the NOV112a protein was found to have homology to the proteins shown in the BLASTP data in Table 112D.
588TABLE 112DPublic BLASTP Results for NOV112aNOV112aIdentities/ProteinResidues/SimilaritiesAccessionMatchfor theExpectNumberProtein/Organism/LengthResiduesMatched PortionValueP11169Solute carrier family 2, facilitated1 . . . 509446/510 (87%)0.0glucose transporter, member 31 . . . 496468/510 (91%)(Glucose transporter type 3, brain) -Homo sapiens (Human), 496 aa.P47842Solute carrier family 2, facilitated1 . . . 507400/507 (78%)0.0glucose transporter, member 31 . . . 494446/507 (87%)(Glucose transporter type 3, brain) -Canis familiaris (Dog), 495 aa.P47843Solute carrier family 2, facilitated1 . . . 505389/505 (77%)0.0glucose transporter, member 31 . . . 492431/505 (85%)(Glucose transporter type 3, brain) -Ovis aries (Sheep), 494 aa.P58352Solute carrier family 2, facilitated1 . . . 505390/505 (77%)0.0glucose transporter, member 31 . . . 492431/505 (85%)(Glucose transporter type 3, brain) -Bos taurus (Bovine), 494 aa.Q07647Solute carrier family 2, facilitated1 . . . 508380/508 (74%)0.0glucose transporter, member 31 . . . 492422/508 (82%)(Glucose transporter type 3, brain) -Rattus norvegicus (Rat), 493 aa.


[0913] PFam analysis predicts that the NOV112a protein contains the domains shown in the Table 112E.
589TABLE 112EDomain Analysis of NOV112aIdentities/SimilaritiesNOV112afor theExpectPfam DomainMatch RegionMatched RegionValueHerpes_glycop: 1 . . . 24940/417(10%)7.2domain 1 of 1171/417(41%)GntP_permease:65 . . . 32970/478(15%)2.5domain 1 of 1185/478(39%)sugar_tr:12 . . . 478188/503(37%)2.2e−158domain 1 of 1410/503(82%)



Example 113

[0914] The NOV113 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 113A.
590TABLE 113ANOV113 Sequence AnalysisSEQ ID NO:3151731 bpNOV113a,ACTACTTCGCCGACACTCGCCAGCCTCGGCTACGAGCAAAAAATGCACCGCACCATGACG59887-01 DNA SequenceGCTCGTTCACCTCGTTTGCCCTGGCCTTTTCCATGGTCTCGATCAACACCGGCGTGGTCACGCTGTTCGCCGACCCGTTCAACCGCGTCGGGGGCATCGGCATCCTCCTGTGGCTGTTGGTGATCCCGCTGGTGTGCTGCATCGTCATGGTCTACTGCCACCTGGCCGGGCGCATTCCGCTCACCGGCTACGCCTACCAATGGTCCAGCCGATTGGCGGGCAATCACTTCGGCTGGTTTACCGGCTGGGTGGCGTTCACCTCGTTTGTCGCCGGTACAGCCGCCACCTCGGCGGCCATCGGTACGGTGTTCGCACCGGAGATCTGGGCCAACCCGACACAGGGTCAGATCCAGGGCCTGAGCATCGGCGCCACGCTGGTGGTGGGCTTGCTGAATATCTGCGGGATTCGCCTGGCCACCCGGATCAACGACATCGGCGCGATCATCGAAATCATCGGCACGGTACTGCTGGCGATTGCGTTGTTCTTCGGGGTGTTTTTCTTCTTTGAGCACACCCAGGGCGTGGCGATCCTGACCTCCGCGCAACCAGTGAGCGGCGGCACGCTCAGCTTCACCACCATCGCCCTCGCCACCTTGCTGCCGGTCTCGGTGCTGCTGGGTTGGGAAGGCGCCGCCGACCTGTCCGAGGAAACCAAGGACCCACGCCGCGCCGCGCCCCGGGCGATGATTCGTGCGGTGCTGGTGTCCAGCGTATTGGGCTTCGTGGTGTTCGCCTTGCTGAGCATCGCGATCCCGGGCTCGGTCAGCGAACTGCTCAGCCACAGCGAAAACCCGGTGATCAATATCGTGCGCCTGCAACTGGGCAATGCCGCCGGCGTGGGCATGATCGTGATCGCTTTCGCCTCGATCCTCGCCTGCCTGATCGCCAACATGGCGGTGGCCACGCGCATGACCTTCGCCCTGTCCCGGGACAACATGCTGCCGGGCTCCAAGGTGCTGGCGAAGATCAACCCGCACTTCGGCACGCCGGTCGCCGCCATCGTGCTGATCACCGCCATCGCCGTGCTGCTGAACCTGGCGAGTGGCGGGTTTGTCACGGCGATCTACTCGATGGTCGGCCTGACCTACTACTGCACTTACCTGCTGACGCTGATTGCCGCGTACCTGGCCTATAAAAACGGCCGGATGCCGGGGGCGCCTGCGGGCGTGTTCAGCCTGGGCCGCTGGTTGCTGCCGATGATTATCCTCGGCGGCCTGTGGGCCATCGCGGTGATCCTGACCCTGAGCGTGCCGGAAGAAAGCCACACTGGCGCTATCACCACCGGGGTTACACTCGGCGTGGGCGTGTTGTGGTGGTTGTTTTCACTGCGCACGCGCCTTAACAATGGCACCGCCGGGCCGAGCGGCAAATTGCTCGACCACTAGCCGCTGATTGCAGCCAAAAGACAAAACCCCGAACACCGGGGTTTTGTCTTGTCACCTCCAAGGAGCTTCCCGATGTTTGAACAGGCCAGCTGGCTCAATCAACCCCAGCATTGGCGCCGAGAAGGCGAGCGACTCAAGGTCCGCACCGATGCCAGTACCGATTTCTGGCGTGAAACCCACTATGGTTTTGTACGCGACAACGGGCATTTCCTGTTTGTTGAAACCGACGGCGACTTTACCGCCCAAGTCAAAATCCACAGTGAGTTTACCCACCTGTATGACCTTCGCORF Start: ATG at 43ORF Stop: TAG at 1441SEQ ID NO:316466 aaMW at 49070.4 kDNOV113a,MHRTMSSFTSFALAFSMVSINTGVVTLFADPFNRVGGIGILLWLLVIPLVCCIVMVYCCG59887-01 Protein SequenceHLAGRIPLTGYAYQWSSRLAGNHFGWFTGWVAFTSFVAGTAATSAAIGTVFAPEIWANPTQGQIQGLSIGATLVVGLLNICGIRLATRINDIGAIIEIIGTVLLAIALFFGVFFFFEHTQGVAILTSAQPVSGGTLSFTTIALATLLPVSVLLGWEGAADLSEETKDPRRAAPRAMIRAVLVSSVLGFVVFALLSIAIPGSVSELLSHSENPVINIVRLQLGNAAGVGMIVIAFASILACLIANMAVATRMTFALSRDNMLPGSKVLAKINPHFGTPVAAIVLITAIAVLLNLASGGFVTAIYSMVGLTYYCTYLLTLIAAYLAYKNGRMPGAPAGVFSLGRWLLPMIILGGLWAIAVILTLSVPEESHTGAITTGVTLGVGVLWWLFSLRTRLNNGTAGPSGKLLDHSEQ ID NO:3171433 bpNOV113b,AAAAATGCACCGCACCATGAGCTCGTTCACCTCGTTTGCCCTGGCCTTTTCCATGGTCCG59887-02 DNA SequenceTCGATCAACACCGGCGTGGTCACGCTGTTCGCCGACCCGTTCAACCGCGTCGGGGGCATCGGCATCCTCCTGTGGCTGTTGGTGATCCCGCTGGTGTGCTGCATCGTCATGGTCTACTGCCACCTGGCCGGGCGCATTCCGCTCACCGGCTACGCCTACCAATGGTCCAGCCGATTGGCGGGCAATCACTTCGGCTGGTTTACCGGCTGGGTGGCGTTCACCTCGTTTGTCGCCGGTACAGCCGCCACCTCGGCGGCCATCGGTACGGTGTTCGCACCGGAGATCTGGGCCAACCCGACACAGGGTCAGATCCAGGGCCTGAGCATCGGCGCCACGCTGGTGGTGGGCTTGCTGAATATCTGCGGGATTCGCCTGGCCACCCGGATCAACGACATCGGCGCGATCATCGAAATCATCGGCACGGTACTGCTGGCGATTGCGTTGTTCTTCGGGGTGTTTTTCTTCTTTGAGCACACCCAGGGCGTGGCGATCCTGACCTCCGCGCAACCAGTGAGCGGCGGCACGCTCAGCTTCACCACCATCGCCCTCGCCACCTTGCTGCCGGTCTCGGTGCTGCTGGGTTGGGAAGGCGCCGCCGACCTGTCCGAGGAAACCAAGGACCCACGCCGCGCCGCGCCCCGGGCGATGATTCGTGCGGTGCTGGTGTCCAGCGTATTGGGCTTCGTGGTGTTCGCCTTGCTGAGCATCGCGATCCCGGGCTCGGTCAGCGAACTGCTCAGCCGCAGCGAAAACCCGGTGATCAATATCGTGCGCCTGCAACTGGGCAATGCCGCCGGCGTGGGCATGGTCGTGATCGCTTTCGCCTCGATCCTCGCCTGCCTGATCGCCAACATGGCGGTGGCCACGCGCATGACCTTCGCCCTGTCCCGGGACAACATGCTGCCGGGCTCCAAGGTGCTGGCGAAGATCAACCCGCACTTCGGCACGCCGGTCGCCGCCATCGTGCTGATCACCGCCATCGCCGTGCTGCTGAACCTGGCGAGTGGCGGGTTTGTCACGGCGATCTACTCGATGGTCGGCCTGACCTACTACTGCACTTACCTGCTGACGCTGATTGCCGCGTACCTGGCCTATAAAAACGGCCGGATGCCGGGGGCGCCTGCGGGCGTGTTCAGCCTGGGCCGCTGGTTGCTGCCGATGATTATCCTCGGCGGCCTGTGGGCCATCGCGGTGATCCTGACCCTGAGCGTGCCGGAAGAAAGCCACACTGGCGCTATCACCACCGGGGTTACACTCGGCGTGGGCGTGTTGTGGTGGTTGTTTTCACTGCGCACGCGCCTTAACAATGGCACCGCCGGGCCGAGCGGCAAATTGCTCGACCACTAGCCGCTGATTGCAGCCAAAAGACAAAACCORF Start: ATG at 5ORF Stop: TAG at 1403SEQ ID NO:318466 aaMW at 49075.4 kDNOV113b,MHRTMSSFTSFALAFSMVSINTGVVTLFADPFNRVGGIGILLWLLVIPLVCCIVMVYCCG59887-02 Protein SequenceHLAGRIPLTGYAYQWSSRLAGNHFGWFTGWVAFTSFVAGTAATSAAIGTVFAPEIWANPTQGQIQGLSIGATLVVGLLNICGIRLATRINDIGAIIEIIGTVLLAIALFFGVFFFFEHTQGVAILTSAQPVSGGTLSFTTIALATLLPVSVLLGWEGAADLSEETKDPRRAAPRAMIRAVLVSSVLGFVVFALLSIAIPGSVSELLSRSENPVINIVRLQLGNAAGVGMVVIAFASILACLIANMAVATRMTFALSRDNMLPGSKVLAKINPHFGTPVAAIVLITAIAVLLNLASGGFVTAIYSMVGLTYYCTYLLTLIAAYLAYKNGRMPGAPAGVFSLGRWLLPMIILGGLWAIAVILTLSVPEESHTGAITTGVTLGVGVLWWLFSLRTRLNNGTAGPSGKLLDH


[0915] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 113B.
591TABLE 113BComparison of NOV113a against NOV113b.Identities/SimilaritiesProteinNOV113a Residues/for theSequenceMatch ResiduesMatched RegionNOV113b1 . . . 466343/466 (73%)1 . . . 466344/466 (73%)


[0916] Further analysis of the NOV113a protein yielded the following properties shown in Table 113C.
592TABLE 113CProtein Sequence Properties NOV113aPSort0.6400 probability located in plasma membrane; 0.4600analysis:probability located in Golgi body; 0.3700 probabilitylocated in endoplasmic reticulum (membrane); 0.1000probability located in endoplasmic reticulum (lumen)SignalPLikely cleavage site between residues 59 and 60analysis:


[0917] A search of the NOV113a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 113D.
593TABLE 113DGeneseq Results for NOV113aNOV113aIdentities/Residues/SimilaritiesGeneseqProtein/Organism/LengthMatchfor theExpectIdentifier[Patent #, Date]ResiduesMatched RegionValueAAG49885Arabidopsis thaliana protein 1 . . . 449122/486 (25%)3e−31fragment SEQ ID NO: 63155 -17 . . . 492217/486 (44%)Arabidopsis thaliana, 504 aa.[EP1033405-A2, 6 SEP 2000]AAG49884Arabidopsis thaliana protein 1 . . . 449122/486 (25%)3e−31fragment SEQ ID NO: 63154 -29 . . . 504217/486 (44%)Arabidopsis thaliana, 516 aa.[EP1033405-A2, 6 SEP 2000]AAG20282Arabidopsis thaliana protein 1 . . . 449122/486 (25%)3e−31fragment SEQ ID NO: 22407 -17 . . . 492217/486 (44%)Arabidopsis thaliana, 504 aa.[EP1033405-A2, 6 SEP 2000]AAG20281Arabidopsis thaliana protein 1 . . . 449122/486 (25%)3e−31fragment SEQ ID NO: 22406 -29 . . . 504217/486 (44%)Arabidopsis thaliana, 516 aa.[EP1033405-A2, 6 SEP 2000]AAG20280Arabidopsis thaliana protein 1 . . . 449122/486 (25%)3e−31fragment SEQ ID NO: 22405 -41 . . . 516217/486 (44%)Arabidopsis thaliana, 528 aa.[EP1033405-A2, 6 SEP 2000]


[0918] In a BLAST search of public sequence databases, the NOV113a protein was found to have homology to the proteins shown in the BLASTP data in Table 113E.
594TABLE 113EPublic BLASTP Results for NOV113aNOV113aIdentities/ProteinResidues/SimilaritiesAccessionMatchfor theExpectNumberProtein/Organism/LengthResiduesMatched PortionValueQ9KZF1PROBABLE AMINO 3 . . . 450139/469 (29%)2e−41ACID/METABOLITE27 . . . 481214/469 (44%)PERMEASE - Streptomycescoelicolor, 504 aa.Q98H14AMINO ACID/METABOLITE 1 . . . 446118/466 (25%)1e−36PERMEASE - Rhizobium loti27 . . . 485209/466 (44%)(Mesorhizobium loti), 518 aa.Q92NI8PUTATIVE AMINO-ACID 1 . . . 449122/475 (25%)1e−32PERMEASE PROTEIN -25 . . . 487204/475 (42%)Rhizobium meliloti (Sinorhizobiummeliloti), 515 aa.O22509PUTATIVE AMINO ACID OR 1 . . . 449122/486 (25%)1e−30GABA PERMEASE - Arabidopsis29 . . . 504217/486 (44%)thaliana (Mouse-ear cress), 516 aa.Q9ZU50PUTATIVE AMINO ACID 1 . . . 449120/487 (24%)2e−28PERMEASE - Arabidopsis thaliana29 . . . 505216/487 (43%)(Mouse-ear cress), 517 aa.


[0919] PFam analysis predicts that the NOV113a protein contains the domains shown in the Table 113F.
595TABLE 113FDomain Analysis of NOV113aIdentities/SimilaritiesNOV113afor theExpectPfam DomainMatch RegionMatched RegionValueoxidored_q3:162 . . . 30728/182(15%)3.7domain 1 of 191/182(50%)ISK_Channel:196 . . . 32632/136(24%)8.8domain 1 of 155/136(40%)ABC2_membrane:122 . . . 37746/273(17%)8.3domain 1 of 1154/273(56%)SSF: domain 1 of 1 7 . . . 39477/470(16%)7.8222/470(47%)Aa_trans: 29 . . . 41767/483(14%)9.7domain 1 of 1236/483(49%)aa_permeases: 1 . . . 45186/516(17%)1.1e−05domain 1 of 1287/516(56%)


[0920] The NOV114 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 114A.
596TABLE 114ANOV114 Sequence AnalysisSEQ ID NO:319876 bpNOV114a,AACTTGCTTTTGGGAGCCAGCGGTATGGCGTCGGGCTGCAAGATTGGCCCGTCCATCCCG59861-01 DNA SequenceTCAACAGCGACCTGGCCAATTTAGGGGCCGAGTGCTCCCGGATGCTAGACTCTGGGGCCGATTATCTGCACCTGGACGTAATGGACGGGCATTTTGTTCCCAACATCACCTTTGGTCACCCTGTGGTGGAAAGCCTTCGAAAGCAGCTAGGCCAGGACCCTTTCTTTGACATGCACATGATGGTGTCCAAGCCAGAACAGTGGGTAAAGCCAATGGCTGTAGCAGGAGCCAATCAGTACACCTTTCATCTCGAGGCTACTGAGAACCCAGGGGCTTTGATTAAAGACATTCGGGAGAATGGGATGAAGGTTGGCCTTGCCATCAAACCAGGAACCTCAGTTGAGTATTTGGCACCATGGGCTAATCAGATAGATATGGCCTTGGTTATGACAGTGGAACCGGGGTTTGGAGGGCAGAAATTCATGGAAGATATGATGCCAAAGGTTCACTGGTTGAGGACCCAGTTCCCATCTTTGGATATAGAGGTCGATGGTGGAGTAGGTCCTGACACTGTCCATAAATGTGCAGAGGCAGGAGCTAACATGATTGTGTCTGGCAGTGCTATTATGAGGAGTGAAGACCCCAGATCTGTGATCAATCTATTAAGAAATGTTTGCTCAGAAGCTGCTCAGAAACGTTCTCTTGATCGGTGAAACCATAAGGAGCCCAGTGTTCCTGTTCATGAAATCTCCCTTTTACTGGAAAACAGGAATATTGACTACCAAATCACAATGCAATTGAAGCCGTACTGCTTTTTTGAGCAGTTATTCATTCCAGTGATTAAAACTGATTGTGCAGAATAAAAAAAAAAAAAAAAAORF Start: ATG at 25ORF Stop: TGA at 709SEQ ID NO:320228 aaMW at 24901.4 kDNOV114a,MASGCKIGPSILNSDLANLGAECSRMLDSGADYLHLDVMDGHFVPNITFGHPVVESLRCG59861-01 Protein SequenceKQLGQDPFFDMHMMVSKPEQWVKPMAVAGANQYTFHLEATENPGALIKDIRENGMKVGLAIKPGTSVEYLAPWANQIDMALVMTVEPGFGGQKFMEDMMPKVHWLRTQFPSLDIEVDGGVGPDTVHKCAEAGANMIVSGSAIMRSEDPRSVINLLRNVCSEAAQKRSLDRSEQ ID NO:321730 bpNOV114b,AACTTGCTTTTGGGAGCCAGCGGTATGGCGTCGGGCTGCAAGATTGGCCCGTCCATCCCG59861-02 DNA SequenceTCAACAGCGACCTGGCCAATTTAGGGGCCGAGTGCCTCCGGATGCTAGACTCTGGGGCCGATTATCTGCACCTGGACGTAATGGACGGGCATTTTGTTCCCAACATCACCTTTGGTCACCCTGTGGTAGAAAGCCTTCGAAAGCAGCTAGGCCAGGACCCTTTCTTTGACATGCACATGATGGTGTCCAAGCCAGAACAGTGGGTAAAGCCAATGGCTGTAGCAGGAGCCAATCAGTACACCTTTCATCTCGAGGCTACTGAGAACCCAGGGGCTTTGATTAAAGACATTCGGGAGAATGGGATGAAGGTTGGCCTTGCCATCAAACCAGGAACCTCAGTTGAGTATTTGGCACCATGGGCTAATCAGATAGATATGGCCTTGGTTATGACAGTGGAACCGGGGTTTGGAGGGCAGAAATTCATGGAAGATATGATGCCAAAGGTTCACTGGTTGAGGACCCAGTTCCCATCTTTGGATATAGAGGTCGATGGTGGAGTAGGTCCTGACACTGTCCATAAATGTGCAGAGGCAGGAGCTAACATGATTGTGTCTGGCAGTGCTATTATGAGGAGTGAAGACCCCAGATCTGTGATCAATCTATTAAGAAATGTTTGCTCAGAAGCTGCTCAGAAACGTTCTCTTGATCGGTGAAACCATAAGGAGCCCAGTGORF Start: ATG at 25ORF Stop: TGA at 709SEQ ID NO:322228 aaMW at 24927.5 kDNOV114b,MASGCKIGPSILNSDLANLGAECLRMLDSGADYLHLDVMDGHFVPNITFGHPVVESLRCG59861-02 Protein SequenceKQLGQDPFFDMHMMVSKPEQWVKPMAVAGANQYTFHLEATENPGALIKDIRENGMKVGLAIKPGTSVEYLAPWANQIDMALVMTVEPGFGGQKFMEDMMPKVHWLRTQFPSLDIEVDGGVGPDTVHKCAEAGANMIVSGSAIMRSEDPRSVINLLRNVCSEAAQKRSLDR


[0921] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 114B.
597TABLE 114BComparison of NOV114a against NOV114b.Identities/SimilaritiesProteinNOV114a Residues/for theSequenceMatch ResiduesMatched RegionNOV114b1 . . . 228227/228 (99%)1 . . . 228227/228 (99%)


[0922] Further analysis of the NOV114a protein yielded the following properties shown in Table 114C.
598TABLE 114CProtein Sequence Properties NOV114aPSort0.6500 probability located in cytoplasm; 0.1753 probabilityanalysis:located in lysosome (lumen); 0.1000 probability located inmitochondrial matrix space; 0.0000 probability located inendoplasmic reticulum (membrane)SignalPNo Known Signal Sequence Predictedanalysis:


[0923] A search of the NOV114a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 114D.
599TABLE 114DGeneseq Results for NOV114aProtein/Organism/LengthNOV114aIdentities/[Patent #,Residues/SimilaritiesGeneseqProtein/Organism/LengthMatchfor theExpectIdentifier[Patent #, Date]ResiduesMatched RegionValueAAM41358Human polypeptide SEQ ID NO1 . . . 228227/228(99%)e−1326289 - Homo sapiens, 247 aa.20 . . . 247 227/228(99%)[WO200153312-A1, 26 JUL2001]AAM41357Human polypeptide SEQ ID NO1 . . . 228227/228(99%)e−1326288 - Homo sapiens, 247 aa.20 . . . 247 227/228(99%)[WO200153312-A1, 26 JUL2001]AAM39571Human polypeptide SEQ ID NO1 . . . 228227/228(99%)e−1322716 - Homo sapiens, 228 aa.1 . . . 228227/228(99%)[WO200153312-A1, 26 JUL2001]AAB71912Human ISOM-4 - Homo sapiens,1 . . . 228227/228(99%)e−132228 aa. [WO200112790-A2, 221 . . . 228227/228(99%)FEB 2001]AAM39572Human polypeptide SEQ ID NO1 . . . 228227/246(92%)e−1292717 - Homo sapiens, 246 aa.1 . . . 246227/246(92%)[WO200153312-A1, 26 JUL2001]


[0924] In a BLAST search of public sequence databases, the NOV114a protein was found to have homology to the proteins shown in the BLASTP data in Table 114E.
600TABLE 114EPublic BLASTP Results for NOV114aNOV114aIdentities/ProteinResidues/SimilaritiesAccessionMatchfor theExpectNumberProtein/Organism/LengthResiduesMatched PortionValueQ96AT9HYPOTHETICAL 24.9 KDA1 . . . 228227/228(99%) e−131PROTEIN - Homo sapiens1 . . . 228227/228(99%)(Human), 228 aa.Q9BSB5HYPOTHETICAL 25.3 KDA1 . . . 228227/228(99%) e−131PROTEIN- Homo sapiens5 . . . 232227/228(99%)(Human), 232 aa (fragment).AAH19126HYPOTHETICAL 24.9 KDA1 . . . 228221/228(96%) e−129PROTEIN - Mus musculus1 . . . 228226/228(98%)(Mouse), 228 aa.O43767RIBULOSE-5-PHOSPHATE-55 . . . 228 174/174(100%)2e−98EPIMERASE - Homo sapiens1 . . . 174174/174(100%)(Human), 174 aa (fragment).Q96N34CDNA FLJ31466 FIS, CLONE69 . . . 228 160/178(89%)2e−86NT2NE2001372, HIGHLY1 . . . 178160/178(89%)SIMILAR TO HOMO SAPIENSPUTATIVE RIBULOSE-5-PHOSPHATE-EPIMERASE -Homo sapiens (Human), 178 aa.


[0925] PFam analysis predicts that the NOV114a protein contains the domains shown in the Table 114F.
601TABLE 114FDomain Analysis of NOV114aIdentities/SimilaritiesPfamNOV114afor theExpectDomainMatch RegionMatched RegionValueRibul_P_3_epim: 6 . . . 20495/209(45%)1.9e−105domain 1 of 1174/209(83%)IGPS: domain 1 of 1179 . . . 21315/35(43%)0.0227/35(77%)trp_syntA: 34 . . . 22245/273(16%)2.9 domain 1 of 1124/273(45%)


[0926] The NOV115 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 115A.
602TABLE 115ANOV115 Sequence AnalysisSEQ ID NO:3231761 bpNOV115a,AGTGTGGTACCTATCTGTCCCCCCTCTGGAGGGGTTGACAAGGGAAAGGGCACCGGGGCG59857-01 DNA SequenceGGCACAGAGATGCAGGACAGATTGCACATCCTGGAGGACCTGAATATGCTCTACATTCGGCAGATGGCACTCAGCCTGGAGGACACGGAGTTGCAGAGGAAGCTAGACCATGAGATCCGGATGAGGGAAGGGGCCTGTAAGCTGCTGGCAGCCTGCTCCCAGCGAGAGCAGGCTCTGGAGGCCACCAAGAGCCTGCTAGTGTGCAACAGCCGCATCCTCAGCTACATGGGCGAGCTGCAGCGGCGCAAGGAGGCGCAGGTGCTGGGGAAGACAAGCCGGCGGCCTTCTGACAGTGGCCCGCCCGCTGAGCGCTCCCCCTGCCGCGGCCGGGTCTGCATCTCTGACCTCCGGATTCCACTCATGTGGAAGGACACAGAATATTTCAAGAACAAAGACTTGCACCGCTGGGCTGTGTTCCTGCTGCTGCAGCTGGGGGAACACATCCAGGACACAGAGATGATCCTAGTGGACAGGACCCTCACAGACATCTCCTTTCAGAGCAATGTGCTCTTCGCTGAGGCGGGGCCAGACTTTGAACTGCGGTTAGAGCTGTATGGGGCCTGTGTGGAAGAAGAGGGGGCCCTGACTGGCGGCCCCAAGAGGCTTGCCACCAAACTCAGCAGCTCCCTGGGCCGCTCCTCAGGGAGGCGTGTCCGGGCATCGCTGGACAGTGCTGGGGGTTCAGGGAGCAGTCCCATCTTGCTCCCCACCCCAGTTGTTGGTGGTCCTCGTTACCACCTCTTGGCTCACACCACACTCACCCTGGCAGCAGTGCAAGATGGATTCCGCACACATGACCTCACCCTTGCCAGTCATGAGGAGAACCCTGCCTGGCTGCCCCTTTATGGTAGCGTGTGTTGCCGTCTGGCAGCTCAGCCTCTCTGCATGACTCAGCCCACTGCAAGTGGTACCCTCAGGGTGCAGCAAGCTGGGGAGATGCAGAACTGGGCACAAGTGCATGGAGTTCTGAAAGGCACAAACCTCTTCTGTTACCGGCAACCTGAGGATGCAGACACTGGGGAAGAGCCGCTGCTTACTATTGCTGTCAACAAGGAGACTCGAGTCCGGGCAGGGGAGCTGGACCAGGCTCTAGGACGGCCCTTCACCCTAAGCATCAGTAACCAGTATGGGGATGATGAGGTGACACACACCCTTCAGACAGAAAGTCGGGAAGCACTGCAGAGCTGGATGGAGGCTCTGTGGCAGCTTTTCTTTGACATGAGCCAATGGAAGCAGTGCTGTGATGAAATCATGAAAATTGAAACTCCTGCTCCCCGGAAACCACCCCAAGCACTGGCAAAGCAGGGGTCCTTGTACCATGAGATGGCTATTGAGCCGCTGGATGACATCGCAGCGGTGACAGACATCCTGACCCAGCGGGAGGGCGCAAGGCTGGAGACACCCCCACCCTGGCTGGCAATGTTTACAGACCAGCCTGCCCTGCCTAACCCCTGCTCGCCTGCCTCAGTGGCCCCAGCCCCAGACTGGACCCACCCCCTGCCCTGGGGGAGACCCCGAACCTTTTCCCTGGATGCTGTCCCCCCAGACCACTCCCCTAGGGCTCGCTCGGTTGCCCCCCTCCCACCTCAGCGATCCCCACGGACCAGAGGCCTCTGCAGCAAAGGCCAACCTCGCACTTGGCTCCAGTCACCAGTGTGAGAGAGAAAGGTGCTGGCATAGGATCTGCCCAGAAGAGAAAATGAORF Start: ATG at 68ORF Stop: TGA at 1715SEQ ID NO:324549 aaMW at 61171.0 kDNOV115a,MQDRLHILEDLNMLYIRQMALSLEDTELQRKLDHEIRMREGACKLLAACSQREQALEACG5987-01 Protein SequenceTKSLLVCNSRILSYMGELQRRKEAQVLGKTSRRPSDSGPPAERSPCRGRVCISDLRIPLMWKDTEYFKNKDLHRWAVFLLLQLGEHIQDTEMILVDRTLTDISFQSNVLFAEAGPDFELRLELYGACVEEEGALTGGPKRLATKLSSSLGRSSGRRVRASLDSAGGSGSSPILLPTPVVGGPRYHLLAHTTLTLAAVQDGFRTHDLTLASHEENPAWLPLYGSVCCRLAAQPLCMTQPTASGTLRVQQAGEMQNWAQVHGVLKGTNLFCYRQPEDADTGEEPLLTIAVNKETRVRAGELDQALGRPFTLSISNQYGDDEVTHTLQTESREALQSWMEALWQLFFDMSQWKQCCDEIMKIETPAPRKPPQALAKQGSLYHEMAIEPLDDIAAVTDILTQREGARLETPPPWLAMFTDQPALPNPCSPASVAPAPDWTHPLPWGRPRTFSLDAVPPDHSPRARSVAPLPPQRSPRTRGLCSKGQPRTWLQSPV


[0927] Further analysis of the NOV115a protein yielded the following properties shown in Table 115B.
603TABLE 115BProtein Sequence Properties NOV115aPSort0.4500 probability located in cytoplasm; 0.3000analysis:probability located in microbody (peroxisome);0.1707 probability located in lysosome (lumen);0.1000 probability located in mitochondrialmatrix spaceSignalPNo Known Signal Sequence Predictedanalysis:


[0928] A search of the NOV115a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 115C.
604TABLE 115CGeneseq Results for NOV115aNOV115aIdentities/Residues/SimilaritiesGeneseqProtein/Organism/LengthMatchfor theExpectIdentifier[Patent #, Date]ResiduesMatched RegionValueAAB35241Human rhotekin - Homo sapiens,24 . . . 549526/527 (99%)0.0563 aa. [US6183990-B1, 6 FEB37 . . . 563526/527 (99%)2001]AAY44559Human Rhotekin protein - Homo24 . . . 549526/527 (99%)0.0sapiens, 563 aa. [WO9958667-A1,37 . . . 563526/527 (99%)18 NOV 1999]AAB35242Human rhotekin EST-derived24 . . . 549522/527 (99%)0.0protein - Homo sapiens, 527 aa. 1 . . . 527523/527 (99%)[US6183990-B1, 6 FEB 2001]AAY44560Human Rhotekin variant protein -24 . . . 549522/527 (99%)0.0Homo sapiens, 527 aa. 1 . . . 527523/527 (99%)[WO9958667-A1, 18 NOV 1999]AAB26790Human Ras correlative GTP24 . . . 549518/527 (98%)0.0binding kinase protein sequence -18 . . . 544519/527 (98%)Homo sapiens, 544 aa.[CN1257924-A, 28 JUN 2000]


[0929] In a BLAST search of public sequence databases, the NOV115a protein was found to have homology to the proteins shown in the BLASTP data in Table 115D.
605TABLE 115DPublic BLASTP Results for NOV115aNOV115aIdentities/ProteinResidues/SimilaritiesAccessionMatchfor theExpectNumberProtein/Organism/LengthResiduesMatched PortionValueAAH17727SIMILAR TO RHOTEKIN - 1 . . . 549549/550 (99%)0.0Homo sapiens (Human), 550 aa. 1 . . . 550549/550 (99%)Q9BST9SIMILAR TO RHOTEKIN -24 . . . 549526/527 (99%)0.0Homo sapiens (Human), 587 aa61 . . . 587526/527 (99%)(fragment).Q96PT6RTKN - Homo sapiens (Human),24 . . . 549518/527 (98%)0.0544 aa.18 . . . 544519/527 (98%)Q9HB05RHOTEKIN - Homo sapiens24 . . . 549505/527 (95%)0.0(Human), 567 aa (fragment).41 . . . 567513/527 (96%)Q61192RHOTEKIN - Mus musculus 1 . . . 549477/551 (86%)0.0(Mouse), 551 aa. 1 . . . 551500/551 (90%)


[0930] PFam analysis predicts that the NOV115a protein contains the domains shown in the Table 115E.
606TABLE 115EDomain Analysis of NOV115aIdentities/SimilaritiesPfamNOV115afor theExpectDomainMatch RegionMatched RegionValueHR1: domain 1 of 123 . . . 9517/87(20%)0.2754/87(62%)PH: domain 1 of 1296 . . . 39719/102(19%)1e−0672/102(71%)



Example 116

[0931] The NOV116 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 116A.
607TABLE 116ANOV116 Sequence AnalysisSEQ ID NO:325450 bpNOV116a,CTGGGAGACTGAAAAAATGCAGACCACCGGGGTATTACTCATTTCTCCAGCTCTGATCCG59855-01 DNA SequenceTGCTGTTGTACCAGGGGTCTAATCAGGCCTGTGTCTGCCTTCTCCTTGAATAGCCCAGAGAATTCATCTAAACAGCCTTCCTACAGCAGCTCCCCACTCCAGGTGGCCAGACGGGAGTTCCAGACCAGTGTTGTCTCCCGGGACACTGACACAGCCGCCAAGTTTATTGGTGCTGGGTCAGCCACAGTTGGTGTGGCTGATTCAGGGGCTGGCATTGGAGCGGTGTTTGGCAGCTTGATTATTGTCTATGCCAGGAAGCTGTCTCTCAAGCAGCAACTCCTCTTCTATGCCATTCTGGGCTTTGCCCTGTCTGAGGCCATGGGGCTCTTCTGTTTGATGATCTCCTTCTTCATCCTGTTCGCCATGTGAGGCTCCGTGAGGGTCACCTGCCTORF Start: ATG at 17ORF Stop: TGA at 425SEQ ID NO:326136 aaMW at 14384.6 kDNOV116a,MQTTGVLLISPALICCCTRGLIRPVSAFSLNSPENSSKQPSYSSSPLQVARREFQTSVCG59855-01 Protein SequenceVSRDTDTAAKFIGAGSATVGVADSGAGIGAVFGSLIIVYARKLSLKQQLLFYAILGFALSEAMGLFCLMISFFILFAMSEQ ID NO:327434 bpNOV116b,ATGCAGACCACCGGGGTATTACTCATTTCTCCAGCTCTGATCTGCTGTTGTACCAGGGCG59855-02 DNA SequenceGTCTAATCAGGCCTGTGTCTGCCTTCTCCTTGAATAGCCCAGAGAATTCATCTAAACAGCCTTCCTACAGCAGCTCCCCACTCCAGGTGGCCAGACGGGAGTTCCAGACCAGTGTTGTCTCCCGGGACACTGACACAGCCGCCAAGTTTATTGGTGCTGGGTCAGCCACAGTTGGTGTGGCTGATTCAGAGGCTGGCATTGGAGCGGTGTTTGGCAGCTTGATTATTGTCTATGCCAGGAAGCTGTCTCTCAAGCAGCAACTCCTCTTCTATGCCATTCTGGGCTTTGCCCTGTCTGAGGCCATGGGGCTCTTCTGTTTGATGATCTCCTTCTTCATCCTGTTCGCCATGTGAGGCTCCGTGAGGGTCACCTGCCTORF Start: ATG AT 1ORF Stop: TGA at 409SEQ ID NO:328136 aaMW at 14456.7 kDNOV116b,MQTTGVLLISPALICCCTRGLIRPVSAFSLNSPENSSKQPSYSSSPLQVARREFQTSVCG59855-02 Protein SequenceVSRDTDTAAKFIGAGSATVGVADSEAGIGAVFGSLIIVYARKLSLKQQLLFYAILGFALSEAMGLFCLMISFFILFAM


[0932] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 116B.
608TABLE 116BComparison of NOV116a against NOV116b.Identities/SimilaritiesProteinNOV116a Residues/for theSequenceMatch ResiduesMatched RegionNOV116b1 . . . 136120/136 (88%)1 . . . 136120/136 (88%)


[0933] Further analysis of the NOV116a protein yielded the following properties shown in Table 116C.
609TABLE 116CProtein Sequence Properties NOV116aPSort0.9190 probability located in plasma membrane; 0.3000analysis:probability located in lysosome (membrane); 0.1888probability located in microbody (peroxisome); 0.1000probability located in endoplasmic reticulum (membrane)SignalPLikely cleavage site between residues 28 and 29analysis:


[0934] A search of the NOV116a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 116D.
610TABLE 116DGeneseq Results for NOV116aNOV116aIdentities/Residues/SimilaritiesGeneseqProtein/Organism/LengthMatchfor theExpectIdentifier[Patent #, Date]ResiduesMatched RegionValueAAG75142Human colon cancer antigen protein1 . . . 136115/136(84%)2e−57SEQ ID NO:5906 - Homo sapiens,7 . . . 142119/136(86%)142 aa. [WO200122920-A2,5 APR 2001]AAB43866Human cancer associated protein1 . . . 136115/136(84%)2e−57sequence SEQ ID NO:1311 - Homo7 . . . 142119/136(86%)sapiens, 142 aa. [WO200055350-Al, 21 SEP 2000]AAU69713Cell death protective sequence CNI-7 . . . 13685/136(62%)2e−3600730, protein #1 - Homo sapiens,7 . . . 14298/136(71%)142 aa. [WO200176532-A2,18 OCT 2001]ABB12016Human ATP synthase subunit7 . . . 13685/136(62%)2e−36homologue, SEQ ID NO:2386 -52 . . . 187 98/136(71%)Homo sapiens, 187 aa.[WO200157188-A2, 9 AUG2001]AAB53428Human colon cancer antigen protein7 . . . 13685/136(62%)2e−36sequence SEQ ID NO:968 - Homo77 . . . 212 98/136(71%)sapiens, 212 aa. [WO200055351 -A1, 21 SEP 2000]


[0935] In a BLAST search of public sequence databases, the NOV116a protein was found to have homology to the proteins shown in the BLASTP data in Table 116E.
611TABLE 116EPublic BLASTP Results for NOV116aNOV115aIdentities/ProteinResidues/SimilaritiesAccessionMatchfor theExpectNumberProtein/Organism/LengthResiduesMatched PortionValueP05496ATP synthase lipid-binding protein,1 . . . 136115/136 (84%)9e−57mitochondrial precursor (EC1 . . . 136119/136 (86%)3.6.1.34) (ATP synthase proteolipidP1) (ATPase protein 9) (ATPasesubunit C) - Homo sapiens (Human),136 aa.P32876ATP synthase lipid-binding protein,1 . . . 136113/136 (83%)1e−54mitochondrial precursor (EC1 . . . 136117/136 (85%)3.6.1.34) (ATP synthase proteolipidP1) (ATPase protein 9) (ATPasesubunit C) - Bos taurus (Bovine), 136aa.P17605ATP synthase lipid-binding protein,1 . . . 136113/136 (83%)2e−54mitochondrial precursor (EC1 . . . 136117/136 (85%)3.6.1.34) (ATP synthase proteolipidP1) (ATPase protein 9) (ATPasesubunit C) - Ovis aries (Sheep), 136aa.Q9CR84ATP SYNTHASE C CHAIN1 . . . 136112/136 (82%)1e−53ISOFORM 1 (EC 3.6.1.34) (LIPID-1 . . . 136117/136 (85%)BINDING PROTEIN) (SUBUNIT C) - Mus musculus (Mouse), 136 aa.P48202ATP synthase lipid-binding protein,1 . . . 136112/136 (82%)1e−53mitochondrial precursor (EC1 . . . 136117/136 (85%)3.6.1.34) (ATP synthase proteolipidP1) (ATPase protein 9) (ATPasesubunit C) - Mus musculus (Mouse),136 aa.


[0936] PFam analysis predicts that the NOV116a protein contains the domains shown in the Table 116F.
612TABLE 116FDomain Analysis of NOV116aIdentities/SimilaritiesPfamNOV116afor theExpectDomainMatch RegionMatched RegionValueATP-synt_C:67 . . . 13531/70 (44%)2.3e−18domain 1 of 157/70 (81%)


[0937] The NOV117 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 117A.
613TABLE 117ANOV117 Sequence AnalysisSEQ ID NO:3291769 bpNOV117a,GAGGTGATGCTGGAGACCTGCGGACTTCTCATGTCTCTGGGCTGTCCTTTGTTCAAACCG59807-01 DNA SequenceCAGAGCTGATCTACCAGTTGGATCACAGACAGGAGCTATGGATGGCTACAAAAGACCTCTCCCAAAGCTCCTATCCAGGTGACAACACAAAACCCAAGACCACAGAGCCTACCTTTTCTCACCTGGCCTTGCCTGAGGAAGTCTTACTCCAGGAACAACTGACACAAGGAGCCTCAAAGAACTCCCAATTAGGGCAATCCAAGGATCAGGATGGGCCATCTGAAATGCAAGAAGTCCACTTGAAAATAGGGATAGGCCCCCAGCGGGGGAAGCTGCTGGAGAAAATGAGTTCTGAACGTGATGGTTTGGGGTCAGATGATGGTGTATGTACAAAGATTACACAGAAACAAGTTTCAACAGAAGGTGATCTCTATGAATGTGATTCACATGGACCAGTTACAGATGCCTTGATTCGCGAAGAGAAAAATTCCTATAAATGTGAGGAATGCGGGAAAGTGTTTAAAAAGAATGCCCTCCTTGTTCAGCATGAACGGATTCACACTCAAGTGAAGCCCTATGAATGCACAGAGTGTGGGAAAACCTTTAGCAAGAGCACTCATCTTCTTCAGCACCTCATCATCCACACTGGGGAGAACCCCTATAAGTGCATGGAGTGTGGGAAGGCTTTTAACCGCAGGTCACACCTCACACGGCACCAGCGGATTCACAGTGGAGAGAAGCCTTATAAGTGCAGTGAATGTGGAAAGGCCTTCACCCACCGCTCCACTTTTGTCTTGCATCACAGGAGCCACACTGGAGAAAAACCCTTTGTGTGCAAAGAGTGTGGCAAAGCCTTTCGAGATAGGCCAGGTTTCATTCGACACTACATCATCCACACGGGAGAGAAGCCCTATGAGTGCATTGAGTGTGGGAAGGCCTTCAACCGCCGGTCATACCTCACGTGGCACCAACAGATTCACACTGGAGTGAAACCCTTTGAATGCAACGAGTGTGGAAAAGCTTTTTGCGAGAGTGCAGACCTCATTCAACACTACATTATCCACACTGGGGAGAAGCCCTATAAGTGCATGGAGTGTGGGAAGGCGTTCAACCGTAGGTCACACCTCAAGCAGCATCAACGGATTCACACTGGGGAGAAGCCTTATGAATGCAGTGAATGTGGAAAGGCCTTCACCCACTGCTCCACTTTTGTCTTGCATAAAAGGACCCACACAGGAGAAAAACCCTATGAATGCAAAGAATGTGGAAAAGCCTTTAGTGATAGGGCAGACCTCATTCGCCACTTCAGCATCCACACTGGAGAGAAACCCTATGAGTGCGTGGAGTGTGGAAAGGCCTTCAACCGCAGCTCACACCTCACGAGGCACCAACAGATTCACACTGGAGAGAAACCCTATGAATGCATCCAGTGTGGGAAAGCCTTTTGCCGGAGCGCAAACCTTATTCGACACTCCATCATTCACACTGGAGAGAAGCCGTATGAATGCAGTGAGTGTGGAAAGGCTTTTAATCGCGGCTCATCCCTCACACATCATCAAAGGATTCATACTGGGAGAAACCCTACCATTGTAACAGATGTGGGAAGACCTTTTATGACTGCACAGACTTCAGTCAACATCCAGGAACTTTTATTAGGGAAAGAGTTTTTGAATATCACCACTGAAGAAAATCTGTGGTGAAAGGGAACATCTTACCATCTGGCCATTCACACTGAAGAGAAACTTCATAAGCATCCTCTCTTTGAGAAAACORF Start: ATG at 7ORF Stop: TGA at 1696SEQ ID NO:330563 aaMW at 64300.6 kDNOV117a,MLETCGLLMSLGCPLFKPELIYQLDHRQELWMATKDLSQSSYPGDNTKPKTTEPTFSHCG59807-01 Protein SequenceLALPEEVLLQEQLTQGASKNSQLGQSKDQDGPSEMQEVHLKIGIGPQRGKLLEKMSSERDGLGSDDGVCTKITQKQVSTEGDLYECDSHGPVTDALIREEKNSYKCEECQKVFKKNALLVQHERTHTQVKPYECTECGKTFSKSTHLLQHLITHTGEKPYKCMECGKAFNRRSHLTRHQRTHSGEKPYKCSECGKAFTHRSTFVLHHRSHTGEKPFVCKECGKAFRDRPGFIRHYIIHTGEKPYECIECGKAFNRRSYLTWHQQIHTGVKPFECNECGKAFCESADLIQHYIIHTGEKPYKCMECGKAFNRRSHLKQHQRIHTGEKPYECSECGKAFTHCSTFVLHKRTHTGEKPYECKECGKAFSDRADLIRHFSIHTGEKPYECVECGKAFNRSSHLTRHQQIHTGEKPYECIQCGKAFCRSANLIRHSIIHTGEKPYECSECGKAFNRGSSLTHHQRIHTGRNPTIVTDVGRPFMTAQTSVNIQELLLGKEFLNITTEENLW


[0938] Further analysis of the NOV117a protein yielded the following properties shown in Table 117B.
614TABLE 117BProtein Sequence Properties NOV117aPsort0.4500 probability located in cytoplasm; 0.3000 probabilityanalysis:located in microbody (peroxisome); 0.1000 probabilitylocated in mitochondrial matrix space; 0.1000 probabilitylocated in lysosome (lumen)SignalPLikely cleavage site between residues 19 and 20analysis:


[0939] A search of the NOV117a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 117C.
615TABLE 117CGeneseq Results for NOV117aNOV117aIdentities/Residues/SimilaritiesGeneseqProtein/Organism/LengthMatchfor theExpectIdentifier[Patent #, Date]ResiduesMatched RegionValueAAM79549Human protein SEQ ID NO 3195 - 1 . . . 563563/566 (99%)0.0Homo sapiens, 603 aa.38 . . . 603563/566 (99%)[WO200157190-A2, 9 AUG 2001]AAM78565Human protein SEQ ID NO 1227 - 1 . . . 563563/566 (99%)0.0Homo sapiens, 603 aa.38 . . . 603563/566 (99%)[WO200157190-A2, 9 AUG2001]ABB21767Protein #3766 encoded by probe for44 . . . 562375/519 (72%)0.0measuring heart cell gene10 . . . 527437/519 (83%)expression - Homo sapiens, 551 aa.[WO200157274-A2, 9 AUG2001]AAM69575Human bone marrow expressed44 . . . 562375/519 (72%)0.0probe encoded protein SEQ ID NO:10 . . . 527437/519 (83%)29881 - Homo sapiens, 551 aa.[WO200157276-A2, 9 AUG 2001]AAM57172Human brain expressed single exon44 . . . 562375/519 (72%)0.0probe encoded protein SEQ ID NO:10 . . . 527437/519 (83%)29277 - Homo sapiens, 551 aa.[WO200157275-A2, 9 AUG 2001]


[0940] In a BLAST search of public sequence databases, the NOV117a protein was found to have homology to the proteins shown in the BLASTP data in Table 117D.
616TABLE 117DPublic BLASTP Results for NOV117aNOV117aIdentities/ProteinResidues/Similarities forAccessionProtein/Matchthe MatchedExpectNumberOrganism/LengthResiduesPortionValueO43296Zinc finger 1 . . . 562401/562 (71%)0.0protein 264 - Homo 43 . . . 603468/562 (82%)sapiens (Human),627 aa.Q96NL3CDNA FLJ30663 1 . . . 535299/535 (55%)0.0FIS, CLONE 38 . . . 572369/535 (68%)SIMILAR TO ZINCFINGER PROTEIN84 - Homo sapiens(Human), 588 aa.Q99676Zinc finger 2 . . . 535261/542 (48%)e−151protein 184 - Homo 58 . . . 595355/542 (65%)sapiens (Human),751 aa.Q96SE7ZINC FINGER151 . . . 541233/391 (59%)e−1481111 - Homo306 . . . 694281/391 (71%)sapiens (Human),839 aa.Q03923Zinc finger protein 1 . . . 535266/544 (48%)e−14885 (Zinc finger 33 . . . 547328/544 (59%)protein HPF4)(HTF1) - Homosapiens (Human),595 aa.


[0941] PFam analysis predicts that the NOV117a protein contains the domains shown in the Table 117E.
617TABLE 117EDomain Analysis of NOV117aIdentities/NOV117aSimilaritiesMatchfor the MatchedExpectPfam DomainRegionRegionValueKRAB: domain 1 of 1 1 . . . 3414/66 (21%)0.1524/66 (36%)zf-C2H2: domain 1 of 13162 . . . 18411/24 (46%)3.6e−0619/24 (79%)zf-C2H2: domain 2 of 13190 . . . 21211/24 (46%)7.1e−0619/24 (79%)zf-C2H2: domain 3 of 13218 . . . 24014/24 (58%)2.3e−0722/24 (92%)zf-BED: domain 1 of 3203 . . . 24113/52 (25%)225/52 (48%)zf-C2H2: domain 4 of 13246 . . . 26811/24 (46%)4.6e−0520/24 (83%)LIM: domain 1 of 1220 . . . 28416/72 (22%)0.6950/72 (69%)zf-C2H2: domain 5 of 13274 . . . 296 8/24 (33%)7.6e−0518/24 (75%)zf-C2H2: domain 6 of 13302 . . . 32411/24 (46%)8.4e−0520/24 (83%)Zn_carbOpept: domain 1312 . . . 330 5/19 (26%)1.2of 117/19 (89%)zf-C2H2: domain 7 of 13330 . . . 352 8/24 (33%)9.7e−0519/24 (79%)zf-C2H2: domain 8 of 13358 . . . 38014/24 (58%)5.3e−0722/24 (92%)zf-BED: domain 2 of 3343 . . . 38112/52 (23%)1.326/52 (50%)zf-C2H2: domain 9 of 13386 . . . 40811/24 (46%)9.4e−0520/24 (83%)zf-C2H2: domain 10 of 13414 . . . 43611/24 (46%)5e−0620/24 (83%)zf-C2H2: domain 11 of 13442 . . . 46412/24 (50%)3e−0722/24 (92%)zf-BED: domain 3 of 3427 . . . 46514/52 (27%)0.3827/52 (52%)zf-C2H2: domain 12 of 13470 . . . 49212/24 (50%)0.0004419/24 (79%)zf-C2H2: domain 13 of 13498 . . . 52012/24 (50%)9.8e−0722/24 (92%)



Example 118

[0942] The NOV118 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 118A.
618TABLE 118ANOV118 Sequence AnalysisSEQ ID NO:3311899 bpNOV118a,CAAACTCTACTACCTCTATATGACATTTCAGGTGTCTGTGACCTTTGATGATGTGGCTCG59805-01 DNA SequenceGTGACTTTCACCCAGGAGGAGTGGGGCCAGCTGGACCTAGCTCAGCGGACCCTGTACCAGGAGGTGATGCTGGAAAACTGTGGGCTCCTGGTATCTCTGGGTGGGTGTCCTGTTCCCAGACCTGAGCTGATCTACCACCTAGAGCATGGGCAGGAGCCATGGACCAGGAAGGAAGACCTCTCCCAAGGCACCTGTCCAGGTGACAAAGGAAAACCCAAGAGCACAGAACCTACCACCTGTGAGCTAGCCTTGTCTGAAGGAATCTCTTTTTGGGGACAACTAACACAAGGAGCTTCAGGGGACTCCCAGTTGGGGCAACCCAAGGATCAGGATGGGTTTTCAGAAATGCAGGGAGAACGCTTGAGACCAGGGTTAGATTCCCAAAAGGAGAAGCTTCCTGGAAAAATGAGCCCCAAACATGATGGTTTAGGGACAGCTGATAGTGTGTGTTCAAGGATTATACAGGATCGAGTCTCCTTAGGAGATGATGTCCATGACTGTGACTCACATGGATCAGGTAAAAATCCAGTTATTCAGGAAGAGGAAAATATCTTTAAATGCAATGAATGTGAAAAAGTGTTTAACAAGAAACGCCTGCTTGCTCGGCATGAGAGGATTCACTCTGGAGTGAAGCCCTATGAATGCACAGAGTGTCGAAAAACCTTTAGCAAGAGTACATACCTCCTGCAGCACCACATGGTCCACACTGGGGAGAAGCCCTATAAGTGCATGGAGTGTGGGAAGGCTTTTAATCGGAAGTCACACCTTACCCAGCACCAGCGGATTCACAGTGGAGAGAAGCCTTATAAGTGCAGTGAATGTGGAAAGGCCTTCACCCACCGCTCCACTTTTGTCTTGCATAACAGGAGCCACACTGGAGAAAAACCCTTTGTGTGCAAAGAGTGTGGCAAAGCCTTTCGAGATAGGCCAGGTTTCATTCGACACTACATCATCCACAGTGGTGAGAATCCCTACGAGTGCTTCGAATGTGGCAAGGTCTTCAAACACAGATCATACCTCATGTGGCACCAGCAGACTCATACCGGGGAGAAGCCCTATGAGTGCAGTGAATGTGGGAAGGCCTTCTGTGAGAGCGCAGCGCTGATTCACCACTATGTCATCCACACTGGAGAGAAGCCCTTTGAGTGCCTCGAGTGTGGGAAGGCTTTCAACCACCGATCCTACCTCAAAAGGCACCAGCGGATTCACACTGGGGAGAAGCCATATGTGTGTAGTGAATGCGGAAAGGCCTTCACCCACTGCTCTACTTTCATCTTGCATAAAAGGGCCCACACTGGAGAAAAACCTTTCGAGTGCAAAGAGTGTGGGAAAGCCTTTAGCAATAGGGCAGACCTCATTCGCCACTTCAGCATCCACACTGGAGAGAAGCCCTATGAGTGCATGGAGTGTGGAAAGGCCTTCAACCGCAGGTCAGGCCTCACAAGGCACCAGCGGATTCATAGTGGAGAGAAGCCCTATGAATGCATCGAGTGTGGGAAAACATTTTGCTGGAGCACAAACCTCATTCGACACTCTATCATCCACACTGGAGAGAAGCCGTATGAGTGCAGTGAATGTGGAAAGGCCTTCAGTCGCAGCTCGTCCCTCACTCAGCATCAAAGGATGCATACTGGGAGAAATCCTATCAGTGTAACAGATGTGGGAAGACCTTTTACAAGTGGGCAGACCTCAGTCAACATCCAAGAACTTTTATTGGGGAAAAACTTTTTGAATGTCACCACTGAGGAAAATCTTTTGCAAGAGGAAGCATCTTACATGGCATCTGATCGTACATACCAAAGAGAAACCCCACAAGTGTCTTCACTGTGAGAAAACCTTCTORF Start: ATG at 20ORF Stop: TGA at 1886SEQ ID NO:332622 aaMW at 70677.2 kDNOV118a,MTFQVSVTFDDVAVTFTQEEWGQLDLAQRTLYQEVMLENCGLLVSLGGCPVPRPELIYCG59805-01 Protein SequenceHLEHGQEPWTRKEDLSQGTCPGDKGKPKSTEPTTCELALSEGISFWGQLTQGASGDSQLGQPKDQDGFSEMQGERLRPGLDSQKEKLPGKMSPKHDGLGTADSVCSRIIQDRVSLGDDVHDCDSHGSGKNPVIQEEENIFKCNECEKVFNKKRLLARHERIHSGVKPYECTECGKTFSKSTYLLQHHMVHTGEKPYKCMECGKAFNRKSHLTQHQRIHSGEKPYKCSECGKAFTHRSTFVLHNRSHTGEKPFVCKECGKAFRDRPGFIRHYIIHSGENPYECFECGKVFKHRSYLMWHQQTHTGEKPYECSECGKAFCESAALIHHYVIHTGEKPFECLECCKAFNHRSYLKRHQRIHTGEKPYVCSECGKAFTHCSTFILHKRAHTGEKPFECKECGKAFSNRADLIRHFSIHTGEKPYECMECGKAFNRRSGLTRHQRIHSGEKPYECIECGKTFCWSTNLIRHSIIHTGEKPYECSECGKAFSRSSSLTQHQRMHTGRNPISVTDVGRPFTSGQTSVNIQELLLGKNFLNVTTEENLLQEEASYMASDRTYQRETPQVSSL


[0943] Further analysis of the NOV118a protein yielded the following properties shown in Table 118B.
619TABLE 118BProtein Sequence Properties NOV118aPSort0.4500 probability located in cytoplasm; 0.3796 probabilityanalysis:located in microbody (peroxisome); 0.1000 probability locatedin mitochondrial matrix space; 0.1000 probability located inlysosome (lumen)SignalPNo Known Signal Sequence Predictedanalysis:


[0944] A search of the NOV118a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 118C.
620TABLE 118CGeneseq Results for NOV118aIdentities/NOV118aSimilaritiesProtein/Organism/Residues/forGeneseqLengthMatchthe MatchedExpectNumber[Patent #, Date]ResiduesPortionValueABB22693Protein #469281 . . . 548468/4680.0encoded by probe 1 . . . 468(100%)for measuring heart468/468cell gene(100%)expression -Homo sapiens,468 aa.[WO200157274-A2,09 AUG. 2001]AAM70526Human bone81 . . . 548468/4680.0marrow expressed 1 . . . 468(100%)probe encoded468/468protein SEQ(100%)ID NO:30832 - Homosapiens, 468 aa.[WO200157276-A2,09 AUG. 2001]AAM58080Human brain81 . . . 548468/4680.0expressed single 1 . . . 468(100%)exon probe encoded468/468protein SEQ ID NO:(100%)30185 - Homosapiens, 468 aa.[WO200157275-A2,09 AUG. 2001]AAM30843Peptide #488081 . . . 548468/4680.0encoded by probe 1 . . . 468(100%)for measuring468/468placental gene(100%)expression - Homosapiens, 468 aa.[WO200157272-A2,09 AUG. 2001]AAM18364Peptide #479881 . . . 548468/4680.0encoded by probe 1 . . . 468(100%)for measuring468/468cervical gene(100%)expression - Homosapiens, 468 aa.[WO200157278-A2,09 AUG. 2001]


[0945] In a BLAST search of public sequence databases, the NOV118a protein was found to have homology to the proteins shown in the BLASTP data in Table 118D.
621TABLE 118DPublic BLASTP Results for NOV118aNOV118aIdentities/ProteinResidues/Similarities forAccessionProtein/Matchthe MatchedExpectNumberOrganism/LengthResiduesPortionValueO43296Zinc finger 4 . . . 622530/619 (85%)0.0sapiens11 . . . 627567/619 (90%)(Human), 627 aa.Q96NL3CDNA FLJ30663 7 . . . 572334/566 (59%)0.0FIS, CLONE 9 . . . 573403/566 (71%)FCBBF1000598,MODERATELYSIMILAR TOZINC FINGERPROTEIN 84 -Homo sapiens(Human), 588 aa.Q99676Zinc finger 2 . . . 571280/604 (46%)e−160protein 184 - Homo23 . . . 623377/604 (62%)sapiens (Human),751 aa.P51523Zinc finger 4 . . . 617286/637 (44%)e−157protein 84 (Zinc 5 . . . 626368/637 (56%)finger proteinHPF2) - Homosapiens (Human),738 aa.Q9BX82EZFIT-RELATED 7 . . . 617278/621 (44%)e−156PROTEIN 1 -14 . . . 626364/621 (57%)Homo sapiens(Human), 626 aa.


[0946] PFam analysis predicts that the NOV118a protein contains the domains shown in the Table 118E.
622TABLE 118EDomain Analysis of NOV118aIdentities/NOV118aSimilaritiesMatchfor the MatchedExpectPfam DomainRegionRegionValueKRAB: domain 1 of 1 7 . . . 7041/66 (62%)2.2e−3354/66 (82%)zf-C2H2: domain 1 of 13198 . . . 22011/24 (46%)3.9e−0517/24 (71%)BolA: domain 1 of 1161 . . . 23814/88 (16%)3.449/88 (56%)zf-C2H2: domain 2 of 13226 . . . 24810/24 (42%)6.2e−0518/24 (75%)zf-C2H2: domain 3 of 13254 . . . 27614/24 (58%)  5e−0722/24 (92%)TFIIS: domain 1 of 1257 . . . 29212/39 (31%)5.721/39 (54%)zf-C2H2: domain 4 of 13282 . . . 30411/24 (46%)3.7e−0520/24 (83%)LIM: domain 1 of 1256 . . . 32014/71 (20%)0.3848/71 (68%)zf-C2H2: domain 5 of 13310 . . . 332 8/24 (33%)7.6e−0518/24 (75%)zf-C2H2: domain 6 of 13338 . . . 36011/24 (46%)1.1e−0519/24 (79%)zf-C2H2: domain 7 of 13366 . . . 388 9/24 (38%)0.0002718/24 (75%)zf-C2H2: domain 8 of 13394 . . . 41612/24 (50%)7.9e−0721/24 (88%)zf-C2H2: domain 9 of 13422 . . . 44410/24 (42%)0.0001419/24 (79%)zf-C2H2: domain 10 of 13450 . . . 47210/24 (42%)8.3e−0620/24 (83%)zf-C2H2: domain 11 of 13478 . . . 50013/24 (54%)  3e−0721/24 (88%)zf-BED: domain 1 of 1463 . . . 50114/52 (27%)0.129/52 (56%)zf-C2H2: domain 12 of 13506 . . . 52811/24 (46%)0.001617/24 (71%)zf-C2H2: domain 13 of 13534 . . . 55613/24 (54%)7.2e−0823/24 (96%)



Example 119

[0947] The NOV119 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 119A.
623TABLE 119ANOV119 Sequence AnalysisSEQ ID NO:3331546 bpNOV119a,GCTCAGTAGGCGTCGGGCTGTGATGCCCCAACTGCTCCAGCGTCTGCAGGCGCGCGCGCG59928-01 DNA SequenceGGCGCGGTAGGCGTACTCGCTGGCCGGATAGCGCGTGATGATGAACTGGTAGGTCTGCGCCGCATCGACGAACAGGCTCTCGCGCTCCAGGCATTGACCGCGCAGCAGGGAAATCTCCGGCTGCAGGTAATTGCGTGAGCGGCTCTTGCGCTCGGCCTGCGACAGCTCCAGCGCGACACGGGCGCAATCGCCTTCGTTGTAGGCGCGATAGGCGTTGTTCAGATGATGGTCGAGCGAGACACGGGTGCAACCCGCAGCAACCAGGGCCACGGCCAGAATGATCAGGTTACGCATGGGCAATTCCTCCAATGAGCAGTGTATCGACAGCCCAGGCAAAAACTGAACAGCGGCAAGCCGACGACGGTTTTTCTGGCGGCGCCTTGGCATGACGCCACTGCCTCTCATTTTATCAACGCCAGCGCCACGACCGCTCGTCCTCTCGAACCAGCGCTAAATCCCCTTCTGCGCTGACCCATATCAATGCCGTTCAGCGCAACAGGGTGTGTAATGTAGGTACAGACTCCAGGCGAGGACGCTGCCATGAAACTGCAACGACTGTTGGTCGTCATCGACGCCGAACACCAGCAACAACCCGCCCTGCAACGCGCAGCCGATGTGGCACGCAAGACCGGCGCCGAATTGCACCTGTTGCAGATCGAATACCACCCAAGCCTGGAAAGCGGCCTGCTGGACAGCCATCTGCTCAACCGCGCCCGTGAAACCATCCTGCGACAGAGCCACGAGGCCCTGCGTGCCAGCGTCGCTCACCTGAGCGATGAAGGATTCAAGATCGCAGTGGACGTGCGCTGGGGCAAACGTCGTCATGAAGAAATCCTCGCCCGCGTCGCGGTGTTGCAACCGGACATCCTGTTCAAGTCGACTCATCCCAGCAGTGCGCTGCGCCGCCTGTTGTTCAGTGATACCAGTTGGCAGCTGATTCGCCGCAGCCCGGTGCCGCTGTGGCTGGTACACGACGCCGAGCCCCATGGTCAGAGCCTGTGCGCTGCGCTCGACCCGCTGCACAGCGCGGACAAACCTGCCGCCCTCGATCATCAGTTGATTGATGCCAGCCAGACCCTGCAGGCCGAGCTCGGCTTACAGGCCCAATACCTGCATGCACAGGCGCCTCTGCCGCGGTCGCTGCTGTTCGACGCCGAGGTAGCGCAGGAATATGAAGACTACGTGACCCAGTGCAGCCGCGAGCACCGCGAAGCCTTCGACAAGCTGATCGCCCAGCACGCCATCGATAGAGCACAGGCCCACCTGTTGGACGGTTTTGCCGAGGAAGTCATCCCGCGTTTCGTGCGTGAGCACAATATAGGCCTGCTGGTGATGGGCGCCATCGCCCGCGGCCATCTGGACAGCCTGCTGATCGGCCACACCGCAGAACGGGTGCTGGAACGTGTCGAGTGCGATCTGCTGGTGATCAAATCGCACGGCAAAGGGTAGTGCACAGGAACAATGACTACAGCCCGACGCCTACTGAGCORF Start: ATG at 599ORF Stop: TAG at 1505SEQ ID NO:334302 aaMW at 33922.3 kDNOV119a,MKLQRLLVVIDAEHQQQPALQRAADVARKTGAELHLLQIEYHPSLESGLLDSHLLNRACG59928-01 Protein SequenceRETILRQSHEALRASVAHLSDEGFKIAVDVRWGKRRHEEILARVAVLQPDILFKSTHPSSALRRLLFSDTSWQLIRRSPVPLWLVHDAEPHGQSLCAALDPLHSADKPAALDHQLIDASQTLQAELGLQAQYLHAQAPLPRSLLFDAEVAQEYEDYVTQCSREEREAFDKLIAQHAIDRAQAHLLDGFAEEVIPRFVREHNIGLLVMGAIARGHLDSLLIGHTAERVLERVECDLLVIKSHGKG


[0948] Further analysis of the NOV119a protein yielded the following properties shown in Table 119B.
624TABLE 119BProtein Sequence Properties NOV119aPSort0.3000 probability located in microbody (peroxisome); 0.3000analysis:probability located in nucleus; 0.2014 probability located inlysosome (lumen); 0.1000 probability located in mitochondrialmatrix spaceSignalPNo Known Signal Sequence Predictedanalysis:


[0949] A search of the NOV119a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 119C.
625TABLE 119CGeneseq Results for NOV119aIdentities/NOV119aSimilaritiesProtein/Organism/Residues/forGeneseqLengthMatchthe MatchedExpectNumber[Patent #, Date]ResiduesPortionValueNo Significant Matches Found


[0950] In a BLAST search of public sequence databases, the NOV119a protein was found to have homology to the proteins shown in the BLASTP data in Table 119D.
626TABLE 119DPublic BLASTP Results for NOV119aNOV119aIdentities/ProteinResidues/Similarities forAccessionProtein/Matchthe MatchedExpectNumberOrganism/LengthResiduesPortionValueQ9HW73HYPOTHETICAL1 . . . 297156/299 (52%)1e−79PROTEIN PA4328 -1 . . . 299200/299 (66%)Pseudomonasaeruginosa, 304 aa.Q9KS28HYPOTHETICAL5 . . . 300 78/302 (25%)4e−29PROTEIN6 . . . 304147/302 (47%)VC1433 -Vibrio cholerae,315 aa.CAC91106PUTATIVE2 . . . 300 93/310 (30%)2e−28STRESS3 . . . 303137/310 (44%)PROTEIN -Yersinia pestis,318 aa.AAL20579PUTATIVE4 . . . 297 91/305 (29%)2e−28UNIVERSAL5 . . . 300139/305 (44%)STRESSPROTEIN -Salmonellatyphimurium LT2,315 aa.CAD01669CONSERVED4 . . . 297 91/305 (29%)3e−28HYPOTHETICAL5 . . . 300139/305 (44%)PROTEIN -Salmonella entericasubsp. entericaserovar Typhi,315 aa.


[0951] PFam analysis predicts that the NOV119a protein contains the domains shown in the Table 119E.
627TABLE 119EDomain Analysis of NOVL19aIdentities/NOV119aSimilaritiesExpectPfam DomainMatch Regionfor the Matched RegionValueUsp: domain 1 of 2 2 . . . 14428/153 (18%)0.001492/153 (60%)Usp: domain 2 of 2160 . . . 29728/153 (18%)0.01388/153 (58%)



Example 120

[0952] The NOV120 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 120A.
628TABLE 120ANOV120 Sequence AnalysisSEQ ID NO:3352202 bpNOV120a,CACCCTCCCGCCCCGCCCCCCGTCCAATGCTGAGCTCAGTCTGCGTCTCGTCCTTCCGCG59947-01 DNA SequenceCGGGCGCCAGGGGGCCAGCAAGCAGCAGCCGGCGCCACCGCCGCAGCCGCCCGAGGTCCCCGGTGGCGACAGCGGCAAGATCGTGATCAACGTGGGCGGCGTGCGCCATGAGACGTACCGCTCGACGCTGCGCACCCTGCCGGGGACGCGGCTGGCCGGCCTGACGGAGCCCGAGGCGGCGGCACGCTTCGACTACGACCCGGGCGCCGACGAGTTCTTCTTTGACCGGCACCCGGGAGTCTTCGCGTACGTGCTCAACTACTACCGCACCGGCAAGCTGCACTGCCCAGCCGACGTGTGCGGGCCCCTGTTTGAGGAGGAGCTCGGCTTCTGGGGCATCGACGAGACCGACGTGGAGGCCTGCTGCTGGATGACCTACCGGCAGCATCGCGACGCTGAGGAGGCGCTCGACTCCTTCGAGGCGCCCGACCCCGCGGGCGCCGCCAACGCCGCCAACGCCGCAGGCGCCCACGACGGAGGCCTGGACGACGAGGCGGGCGCGGGCGGCGGCGGCCTGGACGGAGCGGGCGGCGAGCTCAAGCGCCTCTGCTTCCAGGACGCGGGCGGCGGCGCCGGGGGGCCGCCAGGGGGCGCGGGCGGCGCGGGCGGCACATGGTGGCGCCGCTGGCAGCCCCGCGTGTGGGCGCTCTTCGAGGACCCCTACTCGTCGCGGGCTGCCAGGTATGTGGCCTTCGCCTCCCTCTTCTTCATCCTCATCTCCATCACCACCTTCTGCCTGGAAACCCATGAGGGCTTCATCCATATTAGCAACAAGACGGTGACCCAGGCCTCCCCGATCCCCGGGGCACCTCCGGAGAACATCACCAACGTGGAGGTGGAGACGGAGCCCTTCCTGACCTACGTGGAGGGGGTGTGCGTGGTCTGGTTCACCTTCGAGTTCCTCATGCGCATCACCTTCTGCCCAGACAAGGTGGAGTTTCTTAAAAGCAGCCTCAACATCATCGACTGTGTGGCCATCCTGCCCTTCTATCTCGAGGTGGGCCTCTCGGGCCTCAGCTCCAAGGCCGCCAAAGACGTGCTGGGCTTCCTGCGGGTGGTCCGCTTCGTCCGCATCCTGCGCATCTTCAAGCTGACCCGGCACTTCGTGGGGCTGCGCGTGCTGGGACACACGCTCCGCGCCAGCACCAACGAGTTCCTGCTGCTCATCATCTTCCTGGCCCTGGGGGTGCTCATCTTCGCCACCATGATTTACTACGCTGAGCGCATTGGCGCCGACCCCGATGACATCCTGGGCTCCAACCACACCTACTTCAAGAACATCCCCATTGGCTTCTGGTGGGCTGTGGTCACCATGACGACCCTGGGCTATGGAGACATGTACCCCAAGACGTGGTCGGGGATGCTGGTCGGGGCGCTGTGTGCCCTGGCGGGGGTGCTGACCATCGCCATGCCTGTGCCCGTCATTGTCAACAACTTTGGCATGTACTATTCGCTGGCCATGGCCAAGCAGAAGCTGCCCAAGAAGAAGAACAAACACATCCCCCGGCCCCCGCAACCGGGCTCGCCCAACTACTGCAAGCCTGACCCACCCCCGCCACCCCCGCCCCACCCGCACCACGGCAGCGGGGGCATCAGCCCGCCGCCACCCATCACCCCACCCTCCATGGGGGTGACTGTGGCCGGGGCCTACCCAGCGGGGCCCCACACGCACCCCGGGCTGCTCAGGGGGGGAGCGGGTGGGCTGGGGATCATGGGGCTGCCTCCTCTGCCAGCCCCCGGCGAGCCTTGCCCGTTGGCTCAGGAGGAGGTGATTGAGATCAACCGGGCAGATCCTCGCCCCAATGGGGATCCGGCAGCAGCTGCGCTTGCCCACGAGGACTGCCCAGCCATTGACCAGCCTGCCATGTCCCCGGAAGACAAGAGCCCCATCACGCCTGGAAGCCGTGGCCGCTATAGCCGGGACCGAGCCTGCTTCCTCCTCACCGACTATGCCCCTTCCCCTGATGGCTCCATCCGAAAAGCCACTGGTGCTCCCCCACTGCCCCCCCAAGACTGGCGTAAGCCAGGCCCCCCAAGCTTCTTGCCCGACCTCAACGCCAACGCCGCGGCCTGGATATCCCCCTAGTGGACGAACCCCCTCCCCCCGGGCTCTTGTCACCGCCTGAGACCTCGCGAGACTTTCGORF Start: ATG at 27ORF Stop: TAG at 2142SEQ ID NO:336705 aaMW at 75590.5 kDNOV120a,MLSSVCVSSFRGRQGASKQQPAPPPQPPEVPGGDSGKIVINVGGVRHETYRSTLRTLPCG59947-01 Protein SequenceGTRLAGLTEPEAAARFDYDPGADEFFFDRHPGVFAYVLNYYRTGKLHCPADVCGPLFEEELGFWGIDETDVEACCWMTYRQHRDAEEALDSFEAPDPAGAANAANAAGAHDGGLDDEAGAGGGGLDGAGGELKRLCFQDAGGGAGGPPGGAGGAGGTWWRRWQPRVWALFEDPYSSRAARYVAFASLFFILISITTFCLETHEGFIHISNKTVTQASPIPGAPPENITNVEVETEPFLTYVEGVCVVWFTFEFLMRITFCPDKVEFLKSSLNIIDCVAILPFYLEVGLSGLSSKAAKDVLGFLRVVRFVRILRIFKLTRHFVGLRVLGHTLRASTNEFLLLIIFLALGVLIFATMIYYAERIGADPDDILGSNHTYFKNIPIGFWWAVVTMTTLGYGDMYPKTWSGMLVGALCALAGVLTIAMPVPVIVNNFGMYYSLAMAKQKLPKKKNKHIPRPPQPGSPNYCKPDPPPPPPPHPHHGSGGISPPPPITPPSMGVTVAGAYPAGPHTHPGLLRGGAGGLGIMGLPPLPAPGEPCPLAQEEVIEINRADPRPNGDPAAAALAHEDCPAIDQPAMSPEDKSPITPGSRGRYSRDRACFLLTDYAPSPDGSIRKATGAPPLPPQDWRKPGPPSFLPDLNANAAAWISP


[0953] Further analysis of the NOV120a protein yielded the following properties shown in Table 120B.
629TABLE 120BProtein Sequence Properties NOV120aPSort0.6000 probability located in plasma membrane; 0.5071analysis:probability located in mitochondrial inner membrane;0.4000 probability located in Golgi body; 0.3000 probabilitylocated in endoplasmic reticulum (membrane)SignalPNo Known Signal Sequence Predictedanalysis:


[0954] A search of the NOV120a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 120C.
630TABLE 120CGeneseq Results for NOV120aIdentities/NOV120aSimilaritiesProtein/Organism/Residues/forGeneseqLengthMatchthe MatchedExpectNumber[Patent #, Date]ResiduesRegionValueAAY34120human potassium32 . . . 526371/5100.0channel K + 4 . . . 476(72%)Hnov4 - Homo399/510sapiens, 601 aa.(77%)[WO9943696-A1,02 SEP. 1999]AAY32016Caenorhabditis33 . . . 512217/486 e−113elegans cation27 . . . 465(44%)channel protein -300/486Caenorhabditis(61%)elegans, 556 aa.[WO9947923-A2,23 SEP. 1999]AAB86319Human Kv4.216 . . . 521173/5115e−69protein - Homo22 . . . 441(33%)sapiens, 629 aa.256/511[DE19963612-A1,(49%)12 JUL. 2001]AAY13523Amino acid16 . . . 521173/5118e−68sequence of23 . . . 442(33%)KV4.2FL ion257/511channel protein -(49%)Mammalia, 630 aa.[WO9923880-A1,20 MAY 1999]AAW42996Putative mature17 . . . 510171/5032e−66potassium 4 . . . 425(33%)channel 2240/503protein - Homo(46%)sapiens, 494 aa.[U.S. Pat.No. 5710019-A,20 JAN. 1998]


[0955] In a BLAST search of public sequence databases, the NOV120a protein was found to have homology to the proteins shown in the BLASTP data in Table 120D.
631TABLE 120DPublic BLASTP Results for NOV120aNOV120aIdentities/ProteinResidues/Similarities forAccessionProtein/Matchthe MatchedExpectNumberOrganism/LengthResiduesPortionValueQ14003Voltage-gated 1 . . . 705704/757 (92%)0.0potassium channel 1 . . . 757704/757 (92%)protein Kv3.3(KSHIIID) -Homo sapiens(Human), 757 aa.Q01956Voltage-gated 1 . . . 693663/757 (87%)0.0potassium channel 1 . . . 756668/757 (87%)protein Kv3.3(KSHIIID) - Rattusnorvegicus (Rat),889 aa.Q63959Voltage−gated 1 . . . 671650/725 (89%)0.0potassium channel 1 . . . 724653/725 (89%)protein Kv3.3(KSHIIID) - Musmusculus (Mouse),769 aa.A42073potassium channel32 . . . 607557/576 (96%)0.0protein Kv3.3 -mouse, 679 aa.Q9PVD1KV3.134 . . . 671441/640 (68%)0.0POTASSIUM 6 . . . 547479/640 (73%)CHANNEL -Xenopuslaevis (Africanclawed frog),592 aa.


[0956] PFam analysis predicts that the NOV120a protein contains the domains shown in the Table 120E.
632TABLE 120EDomain Analysis of NOV120aIdentities/NOV120aSimilaritiesMatchfor the MatchedExpectPfam DomainRegionRegionValueK_tetra: domain 1 of 1 36 . . . 137 50/112 (45%)1.6e−47 86/112 (77%)thaumatin: domain 1 of 1314 . . . 319 4/6 (67%)0.7 6/6 (100%)ion trans: domain 1 of 1295 . . . 486 51/231 (22%)2.1e−29155/231 (67%)



Example 121

[0957] The NOV121 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 121A.
633TABLE 121ANOV121 Sequence AnalysisSEQ ID NO:3371943 bpNOV121a,AGATCCACGTGATCTCCAAAGACCCCTGTTGTCTTGTGTTGGGAGGTGGATCCTGAATCG59938-01 DNA SequenceCCACCCAGAGAAGCCTGATACCAATAAAATCCCTGCTTGCTTTCCAGGAGACCCTTGGTCTTCATGTCTTTGGTGTGTGCACTCTTGAACACATGCCAGGCACACAGGGTGCATGACGACAAGCCTAATATTGTCCTAATCATGGTTGATGACCTGGGTATTGGAGATCTGGGCTGCTACGGCAATGACACCATGAGGACGCCTCACATCGACCGCCTTGCCAGGGAAGGCGTGCGACTGACTCAGCACATCTCTGCCCCCTCCCTCTGCAGCCCAAGCCGGTCCGCGTTCTTGACGGGAAGATACCCCATCCGATCAGGTATGGTTTCTAGTGGTAATAGACGTGTCATCCAAAATCTTGCAGTCCCCGCACGCCTCCCTCTTAATGAGACAACACTTGCAGCCTTGCTAAAGAAGCAAGGATACAGCACCGGGCTTATAGGTAACTTAGGCAAATGGCACCTGGGTTTGAGCTGCGCCTCTCGGAATGATCACTGTTACCACCCGCTCAACCATGGTTTTCACTACTTTTACGGGGTGCCTTTTGGACTTTTAAGCGACTGCCAGGCATCCAAGACACCAGAACTGCACCGCTGGCTCAGGATCAAACTGTGGATCTCCACGGTAGCCCTTGCCCTGGTTCCTTTTCTGCTTCTCATTCCCAAGTTCGCCCGCTGGTTCTCAGTGCCATGGAAGGTCATCTTTGTCTTTGCTCTCCTCGCCTTTCTGTTTTTCACTTCCTGGTACTCTAGTTATGGATTTACTCGACGTTGGAATTGCATCCTTATGAGGAACCATGAAATTATCCAGCAGCCAATGAAACACGAGAAAGTAGCTTCCCTCATGCTGAAGCAGGCACTTGCTTTCATTGAAAGGTACAAAAGGGAACCTTTTCTCCTCTTTTTTTCCTTCCTGCACGTACATACTCCACTCATCTCCAAAAAGAAGTTTGTTGGGCGCAGTAAATATGGCAGGTATGCCGACAATGTAGAAGAAATGGATTGGATGGTGGGTGGTAAAATCCTGGATGCCCTGGACCAGGAGCGCCTGGCCAACCACACCTTGGTGTACTTCACCTCTGACAACGGGGGCCACCTGGAGCCCCTCCACGGGGCTGTTCAGCTGGGTGGCTGGAACGGGATCTACAAAGGTGGCAAAGGAATGGGAGGATGGGAAGGAGGTATCCGTCTGCCAGGGATATTCCGGTGGCCGTCAGTCTTGGACGCTGGGAGAGTGATCAATCAGCCCACCAGCTTAATCGACATCTATCCGACGCTGTCTTATATAGGCGGAGGGATCTTGTCCCAGGACAGAGTGATTGACGGCCAGAACCTAATGCCCCTGCTGGAACGAAGGGCGTCCCACTCCGACCACGAGTTCCTCTTCCACTACTGTGGGGTCTATCTGCACACGGTCAGGTGGCATCAGAAGGACACTGTGTGGAAAGCTCATTATGTGACTCCTAAATTCTACCCTGAAGGAACAGGTGCCTGCTATGGGAGTGGAATATGTTCATGTTCGGGCCATGTAACCTACCACCACCCACCACTCCTCTTTGACATCTCAAGAGACCCTTCAGAAGCCCTTCCACTGAACCCTGACAATGAGCCATTATTTGACTCCGTGATCAAAAAGATGGAGGCAGCCATAAGAGAGCATCGTAGGACACTAACACCTGTCCCACAGCAGTTCTCTCTGTTCAACACAATTTGGAAACCATGGCTGCAGCCTTGCTCTGCGACCTTCCCCTTCTGTGGGTGTGACAAGGAAGATGACATCCTTCCCATGGCTCCCTGAGACCATGCGGACCACGTGTTACCCACCACAAACTTACTGTTACAATGGTCATAGGAGCAGAGCTCACCTGACTGATTCATTCCATTTGORF Start: ATG at 122ORF Stop: TGA at 1853SEQ ID NO:338577 aaMW at 65099.5 kDNOV121a,MSLVCALLNTCQAHRVHDDKPNIVLTMVDDLGIGDLGCYGNDTMRTPHIDRLARECVRCG59938-01 Protein SequenceLTQHISAASLCSPSRSAFLTGRYFIRSGMVSSGNRRVIQNLAVPAGLPLNETTLAALLKKQGYSTGLIGKLGKWHLGLSCASRNDHCYHPLNHGFHYFYGVPFGLLSDCQASKTPELHRWLRIKLWISTVALALVPFLLLIPKFARWFSVPWKVIEVFALLAFLFFTSWYSSYGFTRRWNCILMRNHEIIQQPMKEEKVASLMLKEALAFIERYKREPFLLFFSFLHVHTPLISKKKFVGRSKYGRYGDNVEEMDWMVGGKILDALDQERLANHTLVYFTSDNGGHLEPLDGAVQLGGWNGIYKGGKGMGGWEGGIRVPGIFRWPSVLEAGRVINEPTSLMDIYPTLSYIGGGILSQDRVIDGQNLMPLLEGRASHSDHEFLFHYCGVYLHTVRWHQKDTVWKAHYVTPKFYPEGTGACYGSGICSCSGDVTYHDPPLLFDISRDPSEALPLNPDNEPLFDSVIKKMEAAIREHRRTLTPVPQQFSVFNTIWKPWLQPCCGTFPFCGCDKEDDILPMAP


[0958] Further analysis of the NOV121a protein yielded the following properties shown in Table 121B.
634TABLE 121BProtein Sequence Properties NOV121aPSort0.6400 probability located in plasma membrane; 0.4600analysis:probability located in Golgi body; 0.3700 probability locatedin endoplasmic reticulum (membrane); 0.1000 probabilitylocated in endoplasmic reticulum (lumen)SignalPNo Known Signal Sequence Predictedanalysis:


[0959] A search of the NOV121a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 121C.
635TABLE 121CGeneseq Results for NOV121aNOV121aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAM78688Human protein SEQ ID NO 1350- 1 . . . 572388/576 (67%)0.0Homo sapiens, 590 aa.10 . . . 580449/576 (77%)[WO200157190-A2, 9 AUG. 2001]AAM39343Human polypeptide SEQ ID NO20 . . . 571331/555 (59%)0.02488-Homo sapiens, 589 aa.37 . . . 587404/555 (72%)[WO200153312-A1, 26 JUL. 2001]AAM41129Human polypeptide SEQ ID NO20 . . . 571331/555 (59%)0.06060-Homo sapiens, 646 aa.94 . . . 644404/555 (72%)[WO200153312-A1, 26 JUL. 2001]AAY39920Human steroid sulphatase protein20 . . . 569295/559 (52%)e−166sequence-Homo sapiens, 583 aa.26 . . . 575374/559 (66%)[WO9950453-A1, 7 OCT. 1999]AAB51185Human sulfatase protein C SEQ ID20 . . . 569294/559 (52%)e−165NO: 14-Homo sapiens, 583 aa.26 . . . 575372/559 (65%)[U.S. Pat. No. 6153188-A,28 NOV. 2000]


[0960] In a BLAST search of public sequence databases, the NOV121a protein was found to have homology to the proteins shown in the BLASTP data in Table 121D.
636TABLE 121DPublic BLASTP Results for NOV121aNOV121aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueP54793Arylsulfatase F precursor (EC 1 . . . 572379/577 (65%)0.03.1.6.-) (ASF)-Homo sapiens10 . . . 581441/577 (75%)(Human), 591 aa.AAH20229HYPOTHETICAL 64.9 KDA 4 . . . 574358/574 (62%)0.0PROTEIN-Homo sapiens24 . . . 593440/574 (76%)(Human), 593 aa.P51689Arylsulfatase D precursor (EC 4 . . . 574349/574 (60%)0.03.1.6.-) (ASD)-Homo sapiens24 . . . 593429/574 (73%)(Human), 593 aa.P51690Arylsulfatase E precursor (EC20 . . . 571334/555 (60%)0.03.1.6.-) (ASE)-Homo sapiens37 . . . 587405/555 (72%)(Human), 589 aa.P08842Steryl-sulfatase precursor (EC20 . . . 569295/559 (52%)e−1663.1.6.2) (Steroid sulfatase) (Steryl-26 . . . 575374/559 (66%)sulfate sulfohydrolase)(Arylsulfatase C) (ASC)-Homosapiens (Human), 583 aa.


[0961] PFam analysis predicts that the NOV121a protein contains the domains shown in the Table 121E.
637TABLE 121EDomain Analysis of NOV121aIdentities/PfamNOV121aSimilarities forExpectDomainMatch Regionthe Matched RegionValueSulfatase:21 . . . 504231/530 (44%)1e−187domain 1 of 1410/530 (77%)



Example 122

[0962] The NOV122 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 122A.
638TABLE 122ANOV122 Sequence AnalysisSEQ ID NO:3393005 bpNOV122a,ATTTCTTTGGTGTTGTCTTCACAGCTGAACTTGCAAAACAGATTGGAACTTCAAGATTCG59746-01 DNA SequenceATCAATAATCGGAGATACGTATATTTTATTTGTAAAGAAAACATGGCTGCCCTATTCCTACGTGGTTTTGTCCAAATAGGGAACTGCAAGACTGGGATATCTAAGTCAAAAGAAGCATTCATTGAAGCAGTGGAAAGAAAGAAGAAAGATAGACTGGTGCTGTATTTCAAAAGTGGAAAATATAGCACTTTTCCGCTAAGTGATAATATTCAAAATGTAGTCCTTAAATCCTATAGAGGAAACCAAAATCACCTGCATTTAACTTTACAAAATAATAATGCCTTGTTTATTGAAGGATTATCCTCCACAGATGCTGAACAATTGAAGATATTCTTGGACAGAGTTCATCAAAACGAGGTTCAGCCACCTGTGAGACCTGGTAAGGGTGGGAGTGTCTTTTCTAGCACAACACAGAAGGAAATCAACAAAACTTCATTCCAGAAAGTTGATGAGAAATCAAGTAGCAAATCTTTTGAGATAGCAAAAGGAAGTGGGACAGGTGTCCTTCAGAGGATGCCTTTGCTTACATCAAAATTGACACTTACTTGCGGAGAGTTATCAGAAAATCAGCACAAGAAGAGGAAAAGAATGCTCTCATCTAGCTCAGACATCAATGAGGAATTCTTGAAAGAAAATAATTCTGTAGAATACAAGAAATCCAACGCAGATTGTTCGAGGTGTGTAAGCTATAATCGAGAGAAACAATTGAAGTTAAAAGAGTTAGAAGAGAATAAGAAATTGGAATGTGAATCTTCATGCATCATGAACGCCACTGGAAATCCTTACCTACATGACATTGGTCTTCTCCAAGCTCTCACTGAGAAAATGGTTTTGGTATTTCTGTTACAACAAGGGTATAGTGACGGTTACACAAAGTGGGATAAATTAAAACTATTTTTTGAATTATTTCCAGAGAAAATATGCCACGGCCTCCCCAATTTGGGAAACACCTGTTATATGAATGCAGTGTTACAGTCTCTACTTTCAATCCCATCGTTTGCTGATGATTTACTTAATCAGAGTTTCCCATGGGGTAAAATTCCCCTTAATGCTCTTACCATGTGCTTGGCACGGCTACTTTTTTTTAAACATACCTATAATATAGAAATCAAGGAGATGTTACTCTTGAATCTTAAAAAGGCCATTTCAGCAGCTGCAGAGATATTCCATGGCAATGCACAGAACGATGCTCATGAGTTTTTAGCTCACTGTTTAGATGGGAAGATAATTTTCCTAAACAGGTTTTTGCTGATGATCCTGACACCAGTGGGTTTTCTTGCCCTGTCATTACTAATTTTGAGTTAGAGTTGTTGCACTCCATTGCTTGTAAAGCTTGTGGTCAGGTTATTCTCAAGACAGAACTGAATAATTACCTCTCCATCAACCTTCCCCAAAGAATAAAACCACATCCTTCATCTATTCAGTCTACTTTTGATCTTTTTTTTCCAGCAGAAGAGCTTGAGTATAAATCTCCAAAATGTGAGCACAAGACTTCCGTTGCAGTGCACTCATTCAGTAGGCTACCTACAATCCTTATTCTTCACCTCAAACGCTATACCTTGAATCAGTTTTGTGCATTAAACAAGAATGACCAGCAAGTCATCATTTCCAAATATTTAAACGTGTCTTCTCATTGCAATCAACGCACCAGACCACCTCTTCCCTTGAGTGAGGATGGAGAAATTACAGATTTCCAATTATTAAAACTTATTCGAAAGATGACTTCTCCAAACATCACTGTATCATGGCCTGCAACAAAGGAATCCAAAGATATCCTGGCTCCACACATTCGATCAGATAAGCAGTCTGAACAAAAAAAAGGCCAGACAGTCTTTAAAGGGGCAAGCAGAAGACAGCAGCAAAAGTACCTTGGAAAAAATTCTAAACCAAATGAGCTAGAATCTGTATACTCAGGAGATCGAGCATTCATTGAAAAACAACCGTTAGCTCACTTAATGACGTATCTGGAAGATACCTCACTTTGTCAGTTCCACAAAGCTGGAGGTAAACCTCCCAGCAGCCCAGGCACACCTCTCTCAAAAGTTCACTTTCAAACACTGCCCCAAAATCCAAAACCAAAGAAATATGTGAAAACCACTAAGTTTGTACCTTTTGATAGGATTATCAATCCTACTAAAGATTTGTATGAAGATAAAAATATCAGAATTCCAGAAAGATTCCAAAAAGTGTCTGAACAGACTCAGCAGTGTGACGGTATGAGAATCTGTGAACAAGCCCCTCAGCAGGCACTGCCTCAAAGCTTTCCAAAGCCAGGCACCCACGCCCACACAAAGAACCTCCTAACACCTACAAAATTAAATCTACAGAAGTCTAACAGGAATTCCCTACTTGCACTGGGTTCCAATAAGAATCCAAGAAACAAAGACATTTTAGATAAGATAAAATCTAAAGCCAAGGAAACAAAAAGAAATGATGATAAGGGAGATCATACCTACCGGCTCATTAGTGTTGTCAGCCATCTTGGGAACACTCTAAACTCACCCCATTATATCTGTGATCCCTATCACTTTCACAAACACATCTCCTTCACTTACGATGATATCCCGGTGTTACCTATCCAGGAGGCCCAGATGCAGGAGGATAGGCCTTGCACTGGGTACATCTTCTTTTACATGCATAATGAGATCTTTGAAGAGATGTTGAAAAGAGAAGAGAATGCCCAGCTTAATAGCAAGGAGGTAGAGGAGACCCTTCAGAAGGAATAAGAGGAACGTACTCCTCCTTGTACAGATCTCCCTGACTGTCTCACTCGATACCACTTCCTCCATGGAAGGAAAACTGTGAACTTTATCCAGAGATGAAAATGCAATTAGTCTAGGACCAAAGGTCAAACAGAAACACTTAATGGGGAGATCTGCATTCTAATCCORF Start: ATG at 101ORF Stop: TAA at 2840SEQ ID NO:340913 aaMW at 104046.0 kDNOV122a,MAALFLRGFVQIGNCKTGISKSKEAFIEAVERKKKDRLVLYFKSGKYSTFRLSDNIQNCG59746-01 ProteinSequenceVVLKSYRGNQNHLHLTLQNNNGLFIEGLSSTDAEQLKIFLDRVHQNEVQPPVRPGKGGSVFSSTTQKEINKTSFHKVDEKSSSKSFEIAKGSGTGVLQRMPLLTSKLTLTCGELSENQHKKRKRMLSSSSEMNEEFLKENNSVEYKKSKADCSRCVSYNREKQLKLKELEENKKLECESSCIMNATGNPYLDDIGLLQALTEKMVLVFLLQQGYSDGYTKWDKLKLFFELFPEKICHGLPNLGNTCYMNAVLQSLLSIPSFADDLLNQSFPWGKIPLNALTMCLARLLFFKDTYNIEIKEMLLLNLKKAISAAAEIFHGNAQNDAHEFLAHCLDQLKDNMEKLNTIWKPKSEFGEDNFPKQVFADDPDTSGFSCPVITNFELELLHSIACKACGQVILKTELNNYLSINLPQRIKAHPSSIQSTFDLFFGAEELEYKCAKCEHKTSVGVHSFSRLPRILIVHLKRYSLNEFCALKKNDQEVIISKYLKVSSHCNEGTRPPLPLSEDGEITDFQLLKVIRKMTSGNISVSWPATKESKDILAPHIGSDKESEQKKGQTVFKGASRRQQQKYLGKNSKPNELESVYSGDRAFIEKEPLAHLMTYLEDTSLCQFHKAGGKPASSPGTPLSKVDFQTVPENPKRKKYVKTSKFVAFDRIINPTKDLYEDKNIRIPERFQKVSEQTQQCDGMRICEQAPQQALPQSFPKPGTQGHTKNLLRPTKLNLQKSNRNSLLALGSNKNPRNKDILDKIKSKAKETKRNDDKGDHTYRLISVVSHLGKTLKSGHYICDAYDFEKQIWFTYDDMRVLGIQEAQMQEDRRCTGYIFFYMHNEIFEEMLKREENAQLNSKEVEETLQKE


[0963] Further analysis of the NOV122a protein yielded the following properties shown in Table 122B.
639TABLE 122BProtein Sequence Properties NOV122aPSort0.7000 probability located in nucleus; 0.4270 probabilityanalysis:located in mitochondrial matrix space; 0.3000 probabilitylocated in microbody (peroxisome); 0.1047 probability locatedin mitochondrial inner membraneSignalPLikely cleavage site between residues 16 and 17analysis:


[0964] A search of the NOV122a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 122C.
640TABLE 122CGeneseq Results for NOV122aNOV122aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAU07888Polypeptide sequence for human 1 . . . 913913/913 (100%)0.0hspG25-Homo sapiens, 913 aa. 1 . . . 913913/913 (100%)[WO200166752-A2, 13 SEP. 2001]AAB75607Human cancer associated antigen 1 . . . 905429/920 (46%)0.0precursor HOM-TES-84/6 SEQ ID 1 . . . 904566/920 (60%)NO: 6-Homo sapiens, 912 aa.[WO200100874-A2, 4 JAN. 2001]AAU07869Polypeptide sequence for 1 . . . 904335/921 (36%) e−147mammalian Spg25-Mammalia, 1 . . . 834504/921 (54%)835 aa. [WO200166752-A2,13 SEP. 2001]AAG75460Human colon cancer antigen810 . . . 912 61/105 (58%)3e−28protein SEQ ID NO: 6224-Homo 3 . . . 107 79/105 (75%)sapiens, 109 aa. [WO200122920-A2, 5 APR. 2001]AAB39364Gene 8 human secreted protein810 . . . 871 39/64 (60%)5e−15homologous amino acid sequence 1 . . . 64 48/64 (74%)#113-Bos taurus, 64 aa.[WO200057903-A2, 5 OCT. 2000]


[0965] In a BLAST search of public sequence databases, the NOV122a protein was found to have homology to the proteins shown in the BLASTP data in Table 122D.
641TABLE 122DPublic BLASTP Results for NOV122aNOV122aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueQ9BXU7Ubquitin carboxyl-terminal 1 . . . 913913/913 (100%)0.0hydrolase 26 (EC 3.1.2.15) 1 . . . 913913/913 (100%)(Ubiquitin thiolesterase 26)(Ubiquitin-specific processingprotease 26) (Deubiquitinatingenzyme 26)-Homo sapiens(Human), 913 aa.Q9HBJ7UBIQUITIN-SPECIFIC 1 . . . 905429/920 (46%)0.0PROCESSING PROTEASE-Homo 1 . . . 904566/920 (60%)sapiens (Human), 922 aa.Q9HCH8KIAA1594 PROTEIN-Homo50 . . . 912393/932 (42%)e−171sapiens (Human), 931 aa (fragment). 3 . . . 929535/932 (57%)Q99MX1Ubiquitin carboxyl-terminal 1 . . . 904335/921 (36%)e−147hydrolase 26 (EC 3.1.2.15) 1 . . . 834504/921 (54%)(Ubiquitin thiolesterase 26)(Ubiquitin-specific processingprotease 26) (Deubiquitinatingenzyme 26)-Mus musculus(Mouse), 835 aa.Q9ES63UBIQUITIN-SPECIFIC 1 . . . 908341/933 (36%)e−131PROCESSING PROTEASE-Mus 1 . . . 848480/933 (50%)musculus (Mouse), 869 aa.


[0966] PFam analysis predicts that the NOV122a protein contains the domains shown in the Table 122E.
642TABLE 122EDomain Analysis of NOV122aIdentities/PfamNOV122aSimilarities forExpectDomainMatch Regionthe Matched RegionValueUCH-1:295 . . . 32621/32 (66%)8.8e−12domain 1 of 129/32 (91%)UCH-2:820 . . . 88520/72 (28%)2.2e−11domain 1 of 147/72 (65%)



Example 123

[0967] The NOV123 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 123A.
643TABLE 123ANOV123 Sequence AnalysisSEQ ID NO:3412146 bp NOV123a,GAAGGAGCGGGCATGAGGCGCTGCCCGTGCCGTGGGAGCCTGAACGAGGCGGAGGCCGCG88613-01 DNA SequenceGGGCGCTGCCCGCGGCGGCCCGCATGGGACTGGAGGCGCCGCGAGGAGGGCGCCGGCGGCAGCCGGGACAGCAGCGACCTGGGCCCGGCGCAGGGGCCCCGGCGGGGCGGCCGGAGGGGGGCGGGCCCTGGGCCCGGACACAGGGGTCCAGCCTCCACAGCGAGCCTGAGAGGGCCGGCCTCGGGCCTGCGCCGGGGACAGAGAGTCCGCAGGCAGAATTCTGGACAGACGGACAGACTGAGCCCGCGGCAGCTGGCCTTGGAGTAGAGACCGAGAGGCCCAAGCAAAAGACGGAGCCAGACAGGTCCAGCCTCCGGACGCATCTAGAATGGAGCTGGTCAGAGCTGGAGACGACTTGTCTTTGGACGGAGACCGGGACAGATGGCCTTTGGACTGATCCCCACACGTCCGACCTCCAGTTTCAGCCCGAGGAGGCCAGCCCCTGGACACAGCCAGGGGTTCATGGGCCCTGGACAGAGCTGGAAACGCATGCCTCACAGACTCAGCCAGAGAGGGTCAAGTCCTGGGCTGATAACCTCTGGACCCACCAGAACAGTTCCAGCCTCCAGACTCACCCAGAAGGAGCCTGTCCCTCAAAAGAGCCAAGTGCTGATGGCTCCTGGAAAGAATTGTATACTGATGGCTCCAGGACACAACAGGATATTGAAGGTCCCTGGACAGACCCATATACTGATGGCTCCCAGAAAAAACAGGATACTGAAGCAGCCAGGAAACAGCCTGGCACTGGTGGTTTCCAAATACAACAGGATACTGATGGCTCCTGGACACAACCTAGCACTGACGGTTCCCAGACAGCACCTCGGACAGACTGCCTCTTCGGAGAGCCTCAGGATGGCCCATTAGAGGAACCAGAGCCTGGAGAATTCCTCACTCACCTGTACTCTCACCTGAAGTGTAGCCCCCTGTGCCCTGTGCCCCGCCTCATCATTACCCCTGAGACCCCTCAGCCTGAGGCCCAGCCAGTGGGACCCCCCTCCCGGGTTGAGGGGGGCAGCGGCGGCTTCTCCTCTGCCTCTTCTTTCGACGAGTCTGAGGATGACGTGGTCGCCGGGGGCGGAGGTGCCAGCGATCCCGAGGACAGGTCTGGGAGCAAACCCTGGAAGAAGCTGAAGACAGTTCTGAAGTATTCACCCTTTGTGGTCTCCTTCCGAAAACACTACCCTTGCGTCCAGCTTTCTGGACATGCTGGGAACTTCCAGGCAGGAGAGGATGGTCGCATTCTGAAACCTTTCTGTCAGTGTGACCAGCGCAGCCTGGAGCAGCTGATGAAAGACCCGCTGCGACCTTTCGTGCCTGCCTACTATGGCATGGTGCTGCAGGATGGCCAGACCTTCAACCAGATGGAAGACCTCCTGCCTGACTTTGAGGGCCCCTCCATTATGGACTGCAACATGGGCAGCAGCACCTATCTGGAAGAGGAGCTAGTGAAGGCACGGCAACGTCCCCGTCCCCGGAAGGACATCTATGAGAAGATGGTGGCTGTGGACCCTGGGGCCCCTACCCCTGAGGAGCATGCCCAGCGTGCAGTCACCAAGCCCCGCTACATGCAGTGGAGGGAAACCATGAGCTCCACCTCTACCCTGGGCTTCCGGATCGAGGGCATCAAGAAGCCAGATGGGACCTGTAACACCAACTTCAAGAAGACGCAGGCACTGGAGCAGGTGACAAAAGTGCTGGAGGACTTCGTGGATGGAGACCACGTCATCCTGCAAAAGTACGTGGCATGCCTAGAAGAACTTCGTGAAGCTCTGCAGATCTCCCCCTTCTTCAAGACCCACGAGGTGGTAGGCAGCTCCCTCCTCTTCGTGCACGACCACACCGGCCTGGCCAAGGTCTGGATGATAGACTTCGGCAAGACGGTGGCCTTGCCCGACCACCAGACGCTCAGCCACAGGCTGCCCTGGGCTGAGGGCAACCGTGAGGACGGCTACCTCTGGGGCCTGGACAACATGATCTGCCTCCTGCAGGGGCTGGCACAGAGCTGAGCTGCTCAGCCACCATCAGGTTAATTGGATGGCGCCAGTCTGGCTGGAGGAGCCCTGAGATGCCATGGGAGGCCTGAGGTTGORF Start: ATG at 13ORF Stop: TGA at 2062SEQ ID NO:342683 aaMW at 75206.8 kDNOV123a,MRRCPCRGSLNEAEAGALPAAARMGLEAPRGGRRRQPGQQRPGPGAGAPAGRPEGGGPCG88613-01 Protein SequenceWARTEGSSLHSEPERAGLGPAPGTESPQAEFWTDGQTEPAAAGLGVETERPKQKTEPDRSSLRTHLEWSWSELETTCLWTETGTDGLWTDPHRSDLQFQPEEASPWTQPGVHGPWTELETHGSQTQPERVKSWADNLWTHQNSSSLQTHPEGACPSKEPSADGSWKELYTDGSRTQQDIEGPWTEPYTDGSQKKQDTEAARKQPGTGGFQIQQDTDGSWTQPSTDGSQTAPGTDCLLGEPEDGPLEEPEPGELLTHLYSHLKCSPLCPVPRLIITPETPEPEAQPVGPPSRVEGGSGGFSSASSFDESEDDVVAGGGGASDPEDRSGSKPWKKLKTVLKYSPFVVSFRKHYPWVQLSGHAGNFQAGEDGRILKRFCQCEQRSLEQLMKDPLRPFVPAYYGMVLQDGQTFNQMEDLLADFEGPSIMDCKMGSRTYLEEELVKARERPRPRKDMYEKMVAVDPGAPTPEEHAQGAVTKPRYMQWRETMSSTSTLGFRIEGIKKADGTCNTNFKKTQALEQVTKVLEDFVDGDHVILQKYVACLEELREALEISPFFKTHEVVGSSLLFVHDHTGLAKVWMIDFGKTVALPDHQTLSHRLPWAEGNREDGYLWGLDNMICLLQGLAQS


[0968] Further analysis of the NOV123a protein yielded the following properties shown in Table 123B.
644TABLE 123BProtein Sequence Properties NOV123aPSort0.5663 probability located in microbody (peroxisome); 0.3000analysis:probability located in nucleus; 0.1000 probability located inmitochondrial matrix space; 0.1000 probability located inlysosome (lumen)SignalPNo Known Signal Sequence Predictedanalysis:


[0969] A search of the NOV123a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 123C.
645TABLE 123CGeneseq Results for NOV123aNOV123aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAM41393Human polypeptide SEQ ID NO 1 . . . 683682/683 (99%)0.06324-Homo sapiens, 687 aa. 5 . . . 687682/683 (99%)[WO200153312-A1, 26 JUL. 2001]AAM39607Human polypeptide SEQ ID NO 12 . . . 683642/680 (94%)0.02752-Homo sapiens, 711 aa. 36 . . . 711643/680 (94%)[WO200153312-A1, 26 JUL. 2001]AAE04364Human kinase (PKIN)-5-Homo273 . . . 682219/432 (50%)e−117sapiens, 798 aa. [WO200146397-380 . . . 793285/432 (65%)A2, 28 JUN. 2001]


[0970] In a BLAST search of public sequence databases, the NOV123a protein was found to have homology to the proteins shown in the BLASTP data in Table 123D.
646TABLE 123DPublic BLASTP Results for NOV123aNOV121aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueQ96DU7INOSITOL 1,4,5- 1 . . . 683683/683 (100%)0.0TRISPHOSPHATE 3-KINASE C- 1 . . . 683683/683 (100%)Homo sapiens (Human), 683 aa.Q9Y475INOSITOL 1,4,5- 83 . . . 683601/601 (100%)0.0TRISPHOSPHATE 3-KINASE 4 . . . 604601/601 (100%)ISOENZYME (EC 2.7.1.127)-Homo sapiens (Human), 604 aa(fragment).S176821D-myo-inositol-trisphosphate 3-273 . . . 682219/432 (50%)e−117kinase (EC 2.7.1.127) B-human, 54 . . . 467285/432 (65%)472 aa.CAB65055INOSITOL 1,4,5-273 . . . 682219/432 (50%)e−117TRISPHOSPHATE 3-KINASE B-528 . . . 941285/432 (65%)Homo sapiens (Human), 946 aa.Q96JS1INOSITOL 1,4,5-273 . . . 682219/432 (50%)e−117TRISPHOSPHATE 3-KINASE,528 . . . 941285/432 (65%)ISOFORM B (EC 2.7.1.127)-Homo sapiens (Human), 946 aa.


[0971] PFam analysis predicts that the NOV123a protein contains the domains shown in the Table 123E.
647TABLE 123EDomain Analysis of NOV123aIdentities/PfamNOV123aSimilarities forExpectDomainMatch Regionthe Matched RegionValueNo Significant Matches Found



Example 124

[0972] The NOV124 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 124A.
648TABLE 124ANOV124 Sequence AnalysisSEQ ID NO:3431395 bpNOV124a,GGTAAGACGACCTCTGGATGCTCACCCTGCCCTCTTCACCTCTCGTCCCCAGCTGTTTCG59993-01 DNA SequenceCCTCTGCCACCATGAGGAACATTTTCAAGAGGAACCAGGAGCCTATTGTGCCTCCTGCCACCACCACCGCCACGATGCCCATTGGACCCGTCGACAACTCCACTGAGAGTGCCGCTTAAACAAGATTCCCTTACCACCCTGGGCACTGATCGCCATTGCTCTGGTTGCTGGGCTCCTGCTTCTCACCTGCTGCTTCTGCATCTGCAAGAAATGCTGCTGCAAGAAGAAGAAGAACAAGAAGGAGAAGGCCAAAGGCATGAAGAATGCCATGAACATGAAGGACATGAAAGGGGGTCAGGATGACGACGACGCAGAGACACGCCTCACTGAGGGGGAAGGTGAAGGGGAGGAGGAGAAAGAGCCAGAGAACCTGGGCAAACTGCAGTTTTCCCTGGACTATGATTTTCAGGCTAATCAGCTTACTGTGGGCGTTCTGCAGGCTGCTGAACTGCCTGCCCTGGACATGGGAGGCACCTCAGACCCTTATGTCAAGGTCTTCCTCCTTCCTGACAAGAAGAAGAAATATGAGACCAAACTCCATCGGAAGACACTGAACCCTGCCTTCAATGAAACCTTCACCTTCAAGGTGCCATACCAGGAGCTTGGGGGCAAAACTCTGGTGATGGCCATCTATGACTTTGACCGCTTCTCCAAACATGACATCATTGCAGAGGTAAAGGTGCCTATCAACACAGTGGACCTCGGCCAGCCCATTGAGGAGTGGAGAGACCTGCAAGGCGGGGAAAAGCAGGAGCCGGAGAAGCTCGGCGACATCTGCACCTCCCTGCGCTATGTGCCCACGGCCGGGAAGCTCACTGTCTGCATCCTGGAGGCTAAGAACCTCAAGAAGATGGACGTGGGCGGCCTTTCAGACCCGTACGTGAAGATCCACCTGATGCAGAATGGCAAGAGGCTCAAGAAGAAGAAGACAACCGTGAAGAAGAAGACCCTGAACCCATACTTCAACGAGTCCTTCAGCTTTGAGATCCCCTTCGAGCAGATTCACAAAGTCCAGGTAGTCGTCACCGTGCTGGACTATGACAAGCTGCGCAAGAACGAAGCCATACGCAAGATCTTCGTGGGCAGCAATGCCACGGGCACAGAGCTGCGGCACTGGTCCGAGATGCTGGCCAACCCCCGGAGGCCCATCGCCCAGTGGCACTCGCTCAAGCCTGAGGACGAGGTGCATGCACTCCTGGGCAACAACAAGTAGACAGCAGCGGCTGGGACCCCACACCTTTCACGGACACTGACAAGATCCAGAGCTATCAATACCTCAORF Start: ATG at 70ORF Stop: TAG at 1327SEQ ID NO:344419 aaMW at 46871.8 kDNOV124a,MRNIFKRNQEPIVAPATTTATMPIGPVDNSTESGGAGESQEDMFAKLKEKLFNEINKICG59993-01 Protein SequencePLPPWALIAIAVVAGLLLLTCCFCICKKCCCKKKKNKKEKGKGMKNAMNMKDMKGGQDDDDAETGLTEGEGEGEEEKEPENLGKLQFSLDYDFQANQLTVGVLQAAELPALDMGGTSDPYVKVFLLPDKKKKYETKVHRKTLNPAFNETFTFKVPYQELGGKTLVMAIYDFDRFSKHDIIGEVKVPMNTVDLGQPIEEWRDLQGGEKEEPEKLGDICTSLRYVPTAGKLTVCILEAKNLKKMDVGGLSDPYVKIHLMQNGKRLKKKKTTVKKKTLNPYFNESFSFEIPFEQIQKVQVVVTVLDYDKLGKNEAIGKIFVGSNATGTELRHWSDMLANPRRPIAQWHSLKPEEEVDALLGKNKSEQ ID NO:3451338 bpNOV124b,CCACCATGAGGAACATTTTCAAGACGAACCAGGAGCCTATTGTGGCTCCTCCCACCACCG59993-02 DNA SequenceCACCGCCACGATGCCCATTGGACCCGTGGACAACTCCACTGAGAGTGGGGGTGCTGGGGAGAGTCAGGAGGACATCTTTGCCAAACTGAACGAGAAGTTATTCAATGAGATAAACAAGATTCCCTTACCACCCTGGGCACTGATCGCCATTGCTGTGGTTGCTGGGCTCCTGCTTCTCACCTGCTGCTTCTGCATCTGCAAGAAATGCTGCTGCAAGAAGAAGAAGAACAAGAAGGAGAAGGGCAAAGGTATGAAGAATGCCATGAACATGAAGGACATGAAAGGGGGTCAGGATGACGACGACGCAGAGACAGGCCTCACTGAGGGGGAAGGTGAAGGGGAGGAGGAAATCAGCTTACTGTGGGCCTTCTGCAGGCTGCTGAACTGCCTGCCCTGCACATGGGAGGCACCTCACACCCTTATGTCAAGGTCTTCCTCCTTCCTGACAAGAAGAAGAAATATGAGACCAAAGTCCATCGGAAGACACTGAACCCTGCCTTCAATGAAACCTTCACCTTCAAGGTCCCATACCAGGAGCTTGGGGGCAAAACTCTGGTCATGGCCATCTATGACTTTGACCGCTTCTCCAAACATGACATCATTGCAGAGGTAAAGGTGCCTATGAACACAGTGGACCTCGGCCAGCCCATTGAGGAGTGGAGAGACCTGCAAGGCGGCGAAAAGGAGGAGCCGGAGAAGCTGGGCGACATCTGCACCTCCCTGCGCTATGTGCCCACGGCCGGGAAGCTCACTGTCTGCATCCTGGAGGCTAAGAACCTCAAGAAGATGGACCTGGGCGGCCTTTCAGACCCATGAACAAGAAGACCCTGAACCCATACTTCAACGAGTCCTTCAGCTTTGACATCCCCTTCCAGCAGATTCAGAAACTCCAGGTAGTGGTCACCGTGCTGGACTATGACAAGCTGGGCAAGAACGAAGCCATAGGCAAGATCTTCGTGGGCAGCAATGCCACGGGCACACAGCTGCGGCACTGGTCCGACATGCTGGCCAACCCCCGGAGGCCCATCGCCCAGTGGCACTCGCTCAAGCCTGAGGAGGAGGTGGGTGCACTCCTGGGCAAGAACAAGTAGACAGCAGCGGCTGGGACCCCACACCTTTCACGGACACTGACAAGATCCAGAGCTATCAATAAGGTGTAGGCGGORF Start: ATG at 6ORF Stop: TAG at 1263SEQ ID NO:346419 aaMW at 46845.9 kDNOV124b,MRNIFKRNQEPIVAPATTTATMPIGPVDNSTESGGAGESQEDMFAKLKEKLFNEINKICG59993-02 Protein SequencePLPPWALIAIAVVAGLLLLTCCFCICKKCCCKKKKNKKEKGKGMKNAMNMKDMKGGQDDDDAETGLTEGEGEGEEEKEPENLGKLQFSLDYDFQANQLTVGVLQAAELPALDMGGTSDPYVKVFLLPDKKKKYETKVHRKTLNPAFNETFTFKVPYQELGGKTLVMAIYDFDRFSKHDIIGEVKVPMNTVDLGQPIEEWRDLQGGEKEEPEKLGDICTSLRYVPTAGKLTVCILEAKNLKKMDVGGLSDPYVKIHLMQNGKRLKKKKTTVKKKTLNPYFNESFSFEIPFEQIQKVQVVVTVLDYDKLGKNEAIGKIFVGSNATGTELRHWSDMLANPRRPIAQWHSLKPEEEVDALLGKNK


[0973] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 124B.
649TABLE 124BComparison of NOV124a against NOV124b.Identities/ProteinNOV124a Residues/Similarities forSequenceMatch Residuesthe Matched RegionNOV124b1 . . . 419335/419 (79%)1 . . . 419335/419 (79%)


[0974] Further analysis of the NOV124a protein yielded the following properties shown in Table 124C.
650TABLE 124CProtein Sequence Properties NOV124aPSort0.8202 probability located in mitochondrial inneranalysis:membrane; 0.6000 probability located in endoplasmicreticulum (membrane); 0.3500 probability located innucleus; 0.3034 probability located in mitochondrialintermembrane spaceSignalPNo Known Signal Sequence Predictedanalysis:


[0975] A search of the NOV124a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 124D.
651TABLE 124DGeneseq Results for NOV124aNOV124aProtein/Organism/Residues/Identities/GeneseqLength [Patent #,MatchSimilarities forExpectIdentifierDate]Residuesthe Matched RegionValueAAR97722Mouse inositol polyphosphate 1 . . . 419412/422 (97%)0.0binding protein IP4-BP-Mus 1 . . . 422414/422 (97%)musculus, 422 aa. [JP08092290-A,9 APR. 1996]AAU19715Human novel extracellular matrix128 . . . 405141/280 (50%)2e−80protein, Seq ID No 365-Homo169 . . . 447201/280 (71%)sapiens, 461 aa. [WO200155368-A1, 2 AUG. 2001]AAU19714Human novel extracellular matrix141 . . . 409140/273 (51%)3e−74protein, Seq ID No 364-Homo 11 . . . 281193/273 (70%)sapiens, 295 aa. [WO200155368-A1, 2 AUG. 2001]AAW87702A human membrane fusion protein 59 . . . 407146/352 (41%)4e−73designated SYTAX2-Homo 31 . . . 364220/352 (62%)sapiens, 375 aa. [WO9856813-A2,17 DEC. 1998]AAO05534Human polypeptide SEQ ID NO 33 . . . 164127/135 (94%)5e−7019426-Homo sapiens, 149 aa. 15 . . . 149131/135 (96%)[WO200164835-A2, 7 SEP. 2001]


[0976] In a BLAST search of public sequence databases, the NOV124a protein was found to have homology to the proteins shown in the BLASTP data in Table 124E.
652TABLE 124EPublic BLASTP Results for NOV124aNOV124aProteinResidues/Identities/AccessionMatchSimilarities forExpectNumberProtein/Organism/LengthResiduesthe Matched PortionValueP29101Synaptotagmin II (SytII)-Rattus 1 . . . 419411/422 (97%)0.0norvegicus (Rat), 422 aa. 1 . . . 422414/422 (97%)A55417synaptotagmin II-mouse, 422 aa. 1 . . . 419412/422 (97%)0.0 1 . . . 422414/422 (97%)P46097Synaptotagmin II (SytII)-Mus 1 . . . 419411/422 (97%)0.0musculus (Mouse), 422 aa. 1 . . . 422413/422 (97%)P24506Synaptotagmin B (Synaptic vesicle,10 . . . 419341/413 (82%)0.0protein O-P65-B)-Discopyge27 . . . 439366/413 (88%)ommata (Electric ray), 439 aa.P46096Synaptotagmin I (SytI) (p65)-10 . . . 419323/418 (77%)0.0Mus musculus (Mouse), 421 aa. 8 . . . 421353/418 (84%)


[0977] PFam analysis predicts that the NOV124a protein contains the domains shown in the Table 124F.
653TABLE 124FDomain Analysis of NOV124aIdentities/SimilaritiesPfamNOV124afor theExpectDomainMatch RegionMatched RegionValueAdeno_E3_CR2: 62 . . . 10816/50 (32%)6.5domain 1 of 126/50 (52%)C2: domain 1 of 2156 . . . 24254/97 (56%)1.8e−4281/97 (84%)C2: domain 2 of 2287 . . . 37544/97 (45%)2.9e−3980/97 (82%)



Example 125

[0978] The NOV125 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 125A.
654TABLE 125ANOV125 Sequence AnalysisSEQ ID NO:3473226 bpNOV125a,GGACCACTTCTGATGCATCTCTGGGTCCCAACACTATCCACTGCAAGGCCTCGAAACACG59991-01 DNA SequenceGGGGGGCCAGATGGCACCCCCATTTAGCACAAGAGACACGTCCACACTCTGTGAGCCCAAAGGGAGAAGGCTCAGGCCACGGCAGAGACGGAACCAGGAAAACGTCACGAAAAACAGCCTCAAGTTGCCAGGTCCCTTGCAGGAACAGACAGGCCTGGGGCCGCCCCACCTGGGCTCAGAGCTTGCGCTGCATCCAGGTGACACATGGGACTACAACAGTCACGTGATGACCAAATTCGCTGAGGAGGAGGATGTACGTCGTAGTTTTGAAAACACTGCTGCTGACTGGCCGGAAATGCAAACGTTCGCTGGTCCTTTTGATTCAGACCGGTGGGCCTTCCGGCCTCGCACGGTGGTTCTGCACGGAAAGTCAGGAATTGGGAAATCGGCTCTAGCCAGAAGGATCGTGCTGTGCTGGGCGCAAGGTGGACTCTACCAGGGAATGTTCTCCTACGTCTTCTTCCTCCCCGTTAGAGAGATGCAGCGGAAGAACGAGAGCAGTGTCACAGAGTTCATCTCCAGGGAGTGGCCAGACTCCCAGGCTCCGGTGACGGAGATCATGTCCCGACCAGAAAGGCTGTTGTTCATCATTGACGGTTTCGATGACCTGGGCTCTGTCCTCAACAATGACACAAAGCTCTGCAAAGACTGGGCTGAGAACCAGCCTCCGTTCACCCTCATACGCAGTCTGCTGAGGAAGGTCCTGCTCCCTGAGTCCTTCCTGATCGTCACCGTCAGAGACGTGGGCACAGAGCTTGCGTGCGATCATCAACAACCGTGAGCTCCTCCACCAGTGCCAGCTGCCCGCCGTCTGCCGTATGGCTGTGGAGGGAGTGTGGAATAGCAAGTCAGTGTTTGACGGTGACGACCTCATCGTTCAAGGACTCGCCGAGTCTGAGCTCCGTCCTCTCTTTCACATGAACATCCTTCTCCCAGACAGCCACTGTGAGGAGTACTACACCTTCTTCCACCTCAGTCTCCAGGACTTCTGTGCCGCCTTGTACTACGTGTTAGAGGGCCTGGAAATCGAGCCAGCTCTCTGCCCTCTCTACGTTGAGAAGACAAAGAGGTCCATGGAGCTTAAACAGGCAGGCTTCCATATCCACTCCCTTTGGATGAAGCCTTTCTTGTTTGGCCTCGTCACCGAAGACGTAAGGAGGCCACTGGAGGTCCTGCTGGGCTGTCCCGTTCCCCTGGGGGTGAAGCAGAAGCTTCTGCACTGGGTCTCTCTGTTGGGTCAGCAGCCTAATGCCACCACCCCAGGAGACACCCTGGACGCCTTCCACTGTCTTTTCCAGACTCAAGACAAAGAGTTTGTTCGCTTGGCATTAAACAGCTTCCAACAACTGTGGCTTCCGATTAACCAGAACCTGGACTTGATAGCATCTTCCTTCTGCCTCCAGCACTGTCCGTATTTGCGGAAAATTCGGGTGGATGTCAAAGGCATCTTCCCAAGAGATGAGTCCCCTCAGGCATGTCCTCTGGTCCCTCTATGGATGCCGGATAAGACCCTCATTGAGGAGCACTCCCAAGATTTCTGCTCCATGCTTGGCACCCACCCACACCTGCCAAGCTGAGGCATCCCACCTCCAACATACAGACCCTGATGTTTAGAAATGCACAGATTACCCGTGCTGTCCAGCACCTCTGCAGAATCCTCATCGCCAACCGTAACCTAAGATCCCTCAACTTCGGAGGCACCCACCTCAACGAAGAGGATGTAAGGATGCCCTGTGAACCCTTAAAACACCCAAAATGTTTGTTGGAGTCTTTGAGGCTGGATTCCTGTGGATTGACCCATGCCTGTTACCTGAACATCTCCCAAATCCTTACGACCTCCCCCAGCCTCAAATCTCTGAGCCTGGCACGAAACAAGGTGACACACCACGGAGTAATGCCTCTCAGTCATGCCTTGACACTCTCCCAGTGCGCCCTCCACAAGCTGATACTGGAGCACTCTGGCATCACACCCACGGGTTGCCAGAGTCTCGCCTCAGCCCTCGTCAGCAACCGGAGCTTGACACACCTGTCCCTATCCAACAACACCCTGCCGAACGAAGGTGTAAATCTACTCTCTCGATCCATGAGGCTTCCCCACTGTAGTCTGCACAGGCTGATGCTGAATCAGTGCCACCTGGACACGGCTGGCTGTGCTTTTCTTGCACTTCCCCTTATGGGTAACTCATGCCTCACGCACCTGAGCCTTAGCATGAACCCTCTGGAAGACAATGGCCTCAACCTTCTGTGCCAGCTCATGAGAGAACCATCTTGTCATCTCCACCACCTCCACTTGGTAAAGTCTCATCTCACCGCCCCGTGCCGGACAATGCCCTGGGTGACCCTCGCGTTCCTGCACTGTGCCAGCCACTGAAGCAAAACAACACTGTTCTGACCACACTCGGGTTGAAGCCATGTCCACTGACTTCTCATTGCTGTGAGGCACTCTCCTTCCCCCTTTCCTCCAACCGGCATCTGACCAGTCTAAACCTGCTGCAGAATAACTTCACTCCCAAAGGAATGATCAAGCTCTGTTCGGCCTTTCCCTGTCCCACGTCTAACTTACACATAATTCGCCTGTGGAAATGGCAGTACCCTGTCCAAATAACCAAGCTGCTCCACCAAGTGCAGCTACTCAACCCCCGAGTCGTAATTCACGGTAGTTCGCATTCTTTTCATCAACATGACCGGTACTGGTGGAAAAACTGAACATACCCAAACCTGCCCCACTCACACCCATCTGATGGAGGAACTTTAAACCCTGTORF Start: ATG at 69ORF Stop: TGA at 3168SEQ ID NO:3481033 aaMW at 116310.7 kDNOV125a,MGPPFSTRETSTLCEPKGRRLRPRQRRNQENVTKNSLKLPGPLQEQTGLGPPHLGSELCG59991-01 ProteinSequenceGLHGGDTWDYKSHVMTKFAEEEDVRRSFENTAADWPEMQTLAGAFDSDRWGFRPRTVVLHGKSGIGKSALARRIVLCWAQGGLYQGMFSYVFFLPVREMQRKKESSVTEFISREWPDSQAPVTEIMSRPERLLFIIDGFDDLGSVLNNDTKLCKDWAEKQPPFTLIRSLLRKVLLPESFLIVTVRDVGTEKLKSEVVSPRYLLVRGISGEQRIHLLLERGIGEHQKTQGLRAIMNNRELLDQCQVPAVGSLICVALQLQDVVGESVAPFNQTLTGLHAAFVFHQLTPRGVVRRCLNLEERVVLKRFCRMAVEGVWNRKSVFDGDDLMVQGLGESELRALFHMNILLPDSHCEEYYTFFHLSLQDFCAALYYVLEGLEIEPALCPLYVEKTKRSMELKQAGFHIHSLWMKRFLFGLVSEDVRRPLEVLLGCPVPLGVKQKLLHWVSLLGQQPNATTPGDTLDAFHCLFETQDKEFVRLALNSFQEVWLPINQNLDLIASSFCLQHCPYLRKIRVDVKGIFPRDESAEACPVVPLWMRDKTLIEEQWEDFCSMLGTHPHLRQLDLGSSILTERAMKTLCAKLRHPTCKIQTLMFRNAQITPGVQHLWRIVMANRNLRSLNLGGTHLKEEDVRMACEALKHPKCLLESLRLDCCFLTHACYLKISQILTTSPSLKSLSLAGNKVTDQGVMPLSDALRVSQCALQKLILEDCGITATGCQSLASALVSNRSLTHLCLSNNSLGNEGVNLLCRSMRLPHCSLQRLMLNQCHLDTAGCGFLALALMGNSWLTHLSLSMNPVEDNGVKLLCEVMREPSCHLQDLELVKCHLTAACCESLSCVISRSRHLKSLDLTDNALGDGGVAALCEGLKQKNSVLTRLGLKACGLTSDCCEALSLALSCNRHLTSLNLVQNNFSPKGMMKLCSAFACPTSNLQIIGLWKWQYPVQIRKLLEEVQLLKPRVVIDGSWHSFDEDDRYWWKN


[0979] Further analysis of the NOV125a protein yielded the following properties shown in Table 125B.
655TABLE 125BProtein Sequence Properties NOV125aPSort0.7600 probability located in nucleus; 0.3000 probabilityanalysis:located in microbody (peroxisome); 0.1000 probabilitylocated in mitochondrial matrix space; 0.1000 probabilitylocated in lysosome (lumen)SignalPNo Known Signal Sequence Predictedanalysis:


[0980] A search of the NOV125a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 125C.
656TABLE 125CGeneseq Results for NOV125aNOV125aIdentities/Residues/SimilaritiesGeneseqProtein/Organism/LengthMatchfor theExpectIdentifier[Patent #, Date]ResiduesMatched RegionValueAAE07514Human PYRIN-1 protein - Homo103 . . . 934276/843 (32%) e−126sapiens, 1034 aa. [WO200161005- 207 . . . 1003445/843 (52%)A2, 23 AUG 2001]AAE07513Human nucleotide binding site 1114 . . . 935281/839 (33%) e−120(NBS-1) protein - Homo sapiens,180 . . . 990431/839 (50%)1033 aa. [WO200161005-A2,23 AUG 2001]AAU07878Polypeptide sequence for207 . . . 963218/766 (28%)7e−95mammalian Spg65 - Mammalia, 9 . . . 748380/766 (49%)748 aa. [WO200166752-A2,13 SEP 2001]AAE06758Human G-protein coupled receptor- 21 . . . 764235/772 (30%)3e−888 (GCREC-8) protein - Homo219 . . . 959380/772 (48%)sapiens, 1473 aa. [WO200157085-A2, 9 AUG 2001]AAB62571Human CARD-7 polypeptide - 21 . . . 764235/772 (30%)3e−88[WO200130813-A1, 3 MAY 219 . . . 959380/772 (48%)2001]


[0981] In a BLAST search of public sequence databases, the NOV125a protein was found to have homology to the proteins shown in the BLASTP data in Table 125D.
657TABLE 125DPublic BLASTP Results for NOV125aIdentities/ProteinNOV125aSimilaritiesAccessionResidues/for theExpectNumberProtein/Organism/LengthMatch ResiduesMatched PortionValueQ9JLR2MATERNAL-ANTIGEN-THAT- 24 . . . 1033548/1019(53%)0.0EMBRYOS-REQUIRE PROTEIN - 104 . . . 1111716/1019(69%)Mus musculus (Mouse), 1111 aa.Q9R1M5MATER PROTEIN - Mus musculus 24 . . . 1033547/1019(53%)0.0(Mouse), 1111 aa. 104 . . . 1111716/1019(69%)AAL35293NALP4 - Homo sapiens (Human), 63 . . . 958291/907(32%)e−133994 aa. 94 . . . 981473/907(52%)Q96MN2CDNA FLJ32126 FIS, CLONE 63 . . . 958291/907(32%)e−133PEBLM2000112, WEAKLY 19 . . . 906473/907(52%)SIMILAR TO HOMO SAPIENSNUCLEOTIDE-BINDING SITEPROTEIN 1 MRNA - Homosapiens (Human), 919 aa.AAL12497CRYOPYRIN - Homo sapiens103 . . . 934276/843(32%)e−125(Human), 1034 aa. 207 . . . 1003445/843(52%)


[0982] PFam analysis predicts that the NOV125a protein contains the domains shown in the Table 125E.
658TABLE 125EDomain Analysis of NOV125aIdentities/NOV125aSimilaritiesMatchfor thePfam DomainRegionMatched RegionExpect ValueLRR: domain 1 of 6671 . . . 695 6/25 (24%)1.6e+0216/25 (64%)LRR: domain 2 of 6728 . . . 752 7/27 (26%)2.3e+0217/27 (63%)LRR: domain 3 of 6785 . . . 809 7/26 (27%)1.6e+0219/26 (73%)LRR: domain 4 of 6814 . . . 836 6/25 (24%)4.3e+0214/25 (56%)LRR: domain 5 of 6899 . . . 923 8/26 (31%)2720/26 (77%)LRR: domain 6 of 6956 . . . 977 7/25 (28%)2.9e+0216/25 (64%)


[0983] The NOV126 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 126A.
659TABLE 126ANOV126 Sequence AnalysisSEQ ID NO:3492310 bpNOV126a,CCGCGCCTCAGTCCGCCGTCCGCCCTCCGCGCCCGCGCCGCTAGCATGACCGACGCGCCG59987-01 DNA SequenceTGTTGCCCGCGGCCCCCCAGCCGCTGGAGAAGGAGAACGACGGCTACTTTCGGAAGGGCTGTAATCCCCTTGCACAAACCGGCCGGAGTAAATTCCAGAATCAAAGAGCTGCTTTGAATCAGCAGATCCTGAAAGCCGTGCGGATGAGGACCGGAGCGGAAAACCTTCTGTTTGTGGCCACAAACTCAAAGGTGCGGGAGCAAGTGCGGCTGGAGCTGAGCTTCGTCAACTCAGACCTGCAGATGCTCAAGGAAGAGCTGGAGGGGCTGAACATCTCGGTGGGCGTCTATCAGAACACAGAGGAGGCATTTACCATTCCCCTGATTCCTCTTGGCCTGAAGGAAACGAAAGACGTCGACTTTGCAGTCGTCCTCAAGGATTTTATCCTGGAACATTACAGTGAAGATGGCTATTTATATCAAGATGAAATTGCACATCTTATGGATCTGACACAAGCTTGTCGGACGCCTAGCCGGGATGAGGCCGGGGTGGAACTGCTGATGACATACTTCATCCAGCTGGGCTTTGTCGAGAGTCCATTCTTCCCCCCCACACGGCAGATGGGACTCCTGTTCACCTGGTATGACTCTCTCACCGGGGTTCCGGTCAGCCAGCAGAACCTGCTGCTGGAGAAGGCCAGTGTCCTGTTCAACACTGGGGCCCTCTACACCCAGATTGGGACCCGGTGTGATCGGCAGACGCAGGCTGGCCTGGAGAGTGCCATAGATGCCTTTCAGAGAGCCGCAGGGGTTTTAAATTACCTGAAAGACACATTTACCCATACTCCAAGTTACGACATGACCCCTGCCATGCTCAGCGTGCTCGTCAAAATGATGCTTCCACAAGCCCAAGAAAGCGTGTTTGAGAAAATCAGCCTTCCTGCGATCCGGAATGAATTCTTCATGCTGGTGAAGGTGGCTCAGGAGGCAAAGAGAACATCCCCTACTCCTGGGCCAGCTTAGCCTGCGTGAAGGCCCACCACTACGCGGCCCTGCCCCACTACTTCACTGCCATCCTCCTCATCCACCACCAGGTGAAGCCAGGCACGGATCTGGACCACCAGGAGAAGTGCCTGTCCCAGCTCTACGACCACATGCCAGAGGGGCTGACACCCTTGGCCACACTGAAGAATGATCACCACCGCCGACAGCTGGGGAAGTCCCACTTGCGCAGAGCCATGGCTCATCACGAGGAGTCGGTGCCGGAGGCCAGCCTCTGCAAGAAGCTGCCGAGCATTGAGGTGCTACAGAAGGTGCTGTGTGCCGCACAGGAACGCTCCCGGCTCACGTACGCCCACCACCAGGAGGAGGATCACCTGCTGAACCTGATCGACCCCCCCAGAGTGTTGTTGCTAAAACTGAGCAAGAGGTTGACATTATATTGCCCCAGTTCTCCAGCTGACAGTCACGGACTTCTTCCAGAAGCTGGGCCCTTATCTGTGCTGTCGGCTAACAAGCGGTGGACGCCTCCTCGAAGCATCCGCTTCACTGCAGAACAAGGGGACTTGGCGTTCACCTTGAGAGGGAACGCCCCCGTTCACCTTCACTTCCTGGATCCTTACTGCTCTGCCTCGGTGGCAGCAGCCCGGGAAGGAGATTATATTGTCTCCATTCAGCTTGTGGATTGTAAGTGGCTGACGCTGAGTGAGGTTATGAAGCTGCTGAAGAGCTTTGGCGAGGACGAGATCGAAATGAAAGTCGTGAGCCTCCTGGACTCCACATCATCCATGCATAATAAGAGTGCCACATACTCCGTGGGAATGCACAAAACGTACTCCATGATCTGCTTAGCCATTCATGATGACGACAAAACTGATAAAACCAAGAAAATCTCCAAGAAGCTTTCCTTCCTGAGTTGGCTGCACGGCCTCACGTCAAGAAGAAGCTGCCCTCCCCTTTCAGCCTTCTCAACTCAGACACTTCTTGGTACTAATGTGAGGAAACAAACATGTTCAGGCCCCCAACATTTCCGGTGCTGACTCGGCCTTAAACGTTTGTGCCATAATGGAAAATATCTATCTATCTGTTCTCAAATCCTGTTTTTCTCATAGTGTAAACTCACATTTGATGTGTTTTTATGAAGGAAAGTAACCAAGAAACCTCTAGGAATTAGTGAAAAAAGAACTTTTTTGAGGTGORF Start: ATG at 46ORF Stop: TAA at 2104SEQ ID NO:350686 aaMW at 76812.3 kDNOV126a,MTDALLPAAPQPLEKENDGYFRKGCNPLAQTGRSKLQNQRAALNQQILKAVRMRTGAECG59987-01 Protein SequenceNLLKVATNSKVREQVRLELSFVNSDLQMLKEELEGLNISVGVYQNTEEAFTIPLIPLGLKETKDVDFAVVLKDFILEHYSEDGYLYEDEIADLMDLRQACRTPSRDEAGVELLMTYFIQLGFVESRFFPPTRQMGLLFTWYDSLTGVPVSQQNLLLEKASVLFNTGALYTQIGTRCDRQTQAGLESAIDAFQRAAGVLNYLKDTFTHTPSYDMSPAMLSVLVKMMLAQAQESVFEKISLPGIRNEFFMLVKVAQEAAKVGEVYQQLHAAMSQAPVKENIPYSWASLACVKAHHYAALAHYFTAILLIDHQVKPGTDLDHQEKCLSQLYDHMPEGLTPLATLKNDQQRRQLGKSELRRAMAHHEESVREASLCKKLRSIEVLQKVLCAAQERSRLTYAQHQEEDDLLNLIDAPRVLLLKLSKRLTLYCPSSPADSHGLLPEAGPLSVLSANKRWTPPRSIRFTAEEGDLGFTLRGNAPVQVHFLDPYCSASVAGAREGDYIVSIQLVDCKWLTLSEVMKLLKSFGEDEIEMKVVSLLDSTSSMHNKSATYSVGMQKTYSMICLAIDDDDKTDKTKKISKKLSFLSWGTNKNRQKSASTLCLPSVGAARPQVKKKLPSPFSLLNSDSSWYSEQ ID NO:3512109 bpNOV126b,CGCCGCTAGCATGACCGACGCGCTGTTGCCCGCGGCCCCCCAGCCGCTGGAGAAGGAGCG59987-02 DNA SequenceAACGACGGCTACTTTCGGAAGGGCTGTAATCCCCTTGCACAAACCGGCCGGAGTAAATTGCAGAATCAAAGAGCTGCTTTGAATCAGCAGATCCTGAAAGCCGTGCGGATGAGGACCGGAGCGGAAAACCTTCTGAAAGTGGCCACAAACTCAAAGGTGCGGGAGCAAGTGCGGCTGGAGCTGAGCTTCGTCAACTCAGACCTGCAGATCCTCAAGGAAGAGCTGGAGGGGCTGAACATCTCGCTGCGCGTCTATCACAACACAGACGAGGCATTTACGATTCCCCTGATTCCTCTTGGCCTGAACGAAACCAAAGACGTCCACTTTGCACTCCTCCTCAACGATTTTATCCTCGAACATTACAGTGAAGATGGCTATTTATATGAAGATGAAATTGCAGATCTTATGGATCTGAGACAAGCTTGTCCGACGCCTAGCCGGGATGACGCCGGGGTGGAACTGCTGATGACATACTTCATCCAGCTGGGCTTTGTCCACAGTCGATTCTTCCCGCCCACACGGCAGATGGGACTCCTGTTCACCTGGTATGACTCTCTCACCGCGGTTCCGGTCACCCAGCAGAACCTGCTGCTGGAGAAGGCCAGTGTCCTGTTCAACACTGGGGCCCTCTACACCCAGATTCGGACCCGGTGCGATCGGCAGACGCAGGCTGCGCTGGAGACTGCCATAGATGCCTTTCAGAGAGCCGCACGGGTTTTAAATTACCTGAAAGACACATTTACCCATACTCCAAGTTACGACATGAGCCCTGCCATGCTCAGCGTGCTCGTCAAAATGATGCTTCCACAAGCCCAAGAAACCGTGTTTGAGAAAATCAGCCTTCCTCCGATCCCGAATGAATTCTTCATGCTGGTGAAGGTGGCTCAGGAGGCTGCTAAGGTGGGAGACGTCTACCAACAGCTACACCCTGCGTGAAGGCCCACCACTACGCGGCCCTGGCCCACTACTTCACTGCCATCCTCCTCCAGCCATCAGCCAGGCCCCCGTGAAAGACAACATCCCCTACTCCTGGGCCAGCTTAGCATCGACCACCAGGTGAAGCCAGGCACGGATCTGGACCACCAGGACAAGTGCCTGTCCCGCAGCGCCGACAGCTCGGGAAGTCCCACTTGCGCACACCCATCGCTCATCACGAGCAGTCGGTGCGGGAGGCAAGCCTCTGCAAGAAGCTGCGGAGCATTGACGTGCTACAGAAGGTGCTGTGTGCCGCACAGGAACGCTCCCGGCTCACGTACGCCCAGCACCAGGAGGAGGATGACCTGCTGAACCTGATCGACGCCCCCAGTGTTGTTGCTAAAACTGAGCAAGAGGTTGACATTATATTGCCCCAGTTCTCCAAGCTGACAGTCACGGACTTCTTCCAGAACCTCGGCCCCTTATCTGTGTTTTCGGCTAACAAGCGGTGGACGCCTCCTCGAAGCATCCGCTTCACTGCAGAAGAAGGGGACTTGGGGTTCACCTTGAGAGGGAACGCCCCCGTTCAGGTTCACTTCCTCGATCCTTACTCCTCTGCCTCCCTGCCAGGAGCCCGCGAAGGACATTATATTGTCTCCATTCAGCTTCTGGATTGTAAGTCGCTGACGCTGAGTGAGGTTATGAAGCTGCTGAAGAGCTTTGGCGAGGACGAGATCGAGATCAAAGTCGIGAGCCTCCTGGACTCCACATCATCCATGCATAATAAGAGTGCCACATACTCCCTGGGAATGTAGAAAACGTACTCCATGATCTCCTTAGCCATTCATGATGACGACAAAACTGATAAAACCAAGAAAATCTCCAAGAAGCTTTCCTTCCTGAGTTGGGGCACCAACAACAACAGACACAAGTCAGCCAGCACCTTGTGCCTCCCATCGGTCGGGGCTGCACGGCCTCAGGTCAAGAAGAAGCTGCCCTCCCCTTTCACCCTTCTCAACTCACACACTTCTTGGTACTAATGTGAGCAAACAAACATGTTCAGGCCCCGAACATTTCCORF Start: ATG at 11ORF Stop: TAG at 1844SEQ ID NO:352611 aaMW at 68613.9 kDNOV126b,MTDALLPAAPQPLEKENDGYFRKGCNPLAQTGRSKLQNQRAALNQQILKAVRMRTGAECG59987-02 Protein SequenceNLLKVATNSKVREQVRLELSFVNSDLQMLKEELEGLNISVGVYQNTEEAFTIPLIPLGLKETKDVDFAVVLKDFILEHYSEDGYLYEDEIADLMDLRQACRTPSRDEAGVELLMTYFIQLGFVESRFFPPTRQMGLLFTWYDSLTGVPVSQQNLLLEKASVLFNTGALYTQIGTRCDRQTQAGLESAIDAFQRAAGVLNYLKDTFTHTPSYDMSPAMLSVLVKMMLAQAQESVFEKISLPGIRNEFFMLVKVAQEAAKVGEVYQQLHAAMSQAPVKENIPYSWASLACVKAHHYAALAHYFTAILLIDHQVKPGTDLDHQEKCLSQLYDHMPEGLTPLATLKNDQQRRQLGKSELRRAMAHHEESVREASLCKKLRSIEVLQKVLCAAQERSRLTYAQHQEEDDLLNLIDAPRVLLLKLSKRLTLYCPSSPADSHGLLPEAGPLSVLSANKRWTPPRSIRFTAEEGDLGFTLRGNAPVQVHFLDPYCSASVAGAREGDYIVSIQLVDCKWLTLSEVMKLLKSFGEDEIEMKVVSLLDSTSSMHNKSATYSVGM


[0984] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 126B.
660TABLE 126BComparison of NOV126a against NOV126b.Identities/SimilaritiesProteinNOV126a Residues/for theSequenceMatch ResiduesMatched RegionNOV126b1 . . . 611585/612 (95%)1 . . . 611590/612 (95%)


[0985] Further analysis of the NOV126a protein yielded the following properties shown in Table 126C.
661TABLE 126CProtein Sequence Properties NOV126aPSort0.4500 probability located in cytoplasm; 0.3000 probabilityanalysis:located in microbody (peroxisome); 0.1000 probability locatedin mitochondrial matrix space; 0.1000 probability located inlysosome (lumen)SignalPNo Known Signal Sequence Predictedanalysis:


[0986] A search of the NOV126a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 126D.
662TABLE 126DGeneseq Results for NOV126aNOV126aIdentities/Residues/SimilaritiesGeneseqProtein/Organism/LengthMatchfor theExpectIdentifier[Patent #, Date]ResiduesMatched RegionValueAAU10192Human prostate specific protein1 . . . 686660/687(96%)0.0PSL22 - Homo sapiens, 686 aa.1 . . . 686665/687(96%)[WO200172962-A2, 4 OCT 2001]AAB68561Human GTP-binding associated27 . . . 686 626/661(94%)0.0protein #61 - Homo sapiens, 666 aa.7 . . . 666633/661(95%)[WO200105970-A2, 25 JAN 2001]AAG64579Human transcription termination201 . . . 686 458/487(94%)0.0factor binding protein 54 - Homo3 . . . 488464/487(95%)sapiens, 488 aa. [CN1297918-A,6 JUN 2001]AAB29661Human histidine domain-protein110 . . . 357 82/252(32%)3e−28tyrosine phosphatase, SEQ ID NO:27 . . . 253135/252(53%)[WO200063392-A1, 26 OCT 2000]AAU00869Human cancer related protein 5 -409 . . . 597 70/189(37%)2e−27Homo sapiens, 257 aa.8 . . . 196102/189(53%)[WO200118014-A1, 15 MAR2001]


[0987] In a BLAST search of public sequence databases, the NOV126a protein was found to have homology to the proteins shown in the BLASTP data in Table 126E.
663TABLE 126EPublic BLASTP Results for NOV126aNOV126aIdentities/ProteinResidues/SimilaritiesAccessionMatchfor theExpectNumberProtein/Organism/LengthResiduesMatched PortionValueQ96RU1RHOPHILIN-LIKE PROTEIN - 1 . . . 686627/688 (91%)0.0Homo sapiens (Human), 685 aa. 1 . . . 685640/688 (92%)Q9DBN21300002E07RIK PROTEIN - 1 . . . 686573/687 (83%)0.0Mus musculus (Mouse), 686 aa. 1 . . . 686616/687 (89%)Q61085GTP-RHO binding protein 116 . . . 596273/583 (46%) e−135(Rhophilin) - Mus musculus20 . . . 580361/583 (61%)(Mouse), 643 aa.Q9XYY9RHOPHILIN - Drosophila21 . . . 615248/654 (37%) e−110melanogaster (Fruit fly), 718 aa.31 . . . 674363/654 (54%)Q96PV9KIAA1929 PROTEIN - Homo23 . . . 366178/346 (51%)1e−93sapiens (Human), 410 aa17 . . . 362241/346 (69%)(fragment).


[0988] PFam analysis predicts that the NOV126a protein contains the domains shown in the Table 126F.
664TABLE 126FDomain Analysis of NOV126aIdentities/SimilaritiesPfamNOV126afor theExpectDomainMatch RegionMatched RegionValueHR1: domain 1 of 1 38 . . . 11019/87(22%)1.2e−0553/87(61%)BRO1: domain 1 of 1111 . . . 26360/172(35%)3.8e−56125/172(73%)PDZ: domain 1 of 1516 . . . 59320/84(24%)0.4653/84(63%)



Example 127

[0989] The NOV127 clone was analyzed, and the nucleotide and predicted polypeptide sequences are shown in Table 127A.
665TABLE 127ANOV127 Sequence AnalysisSEQ ID NO:3533351 bpNOV127a,CGTCCCGTGGCCATGACGACCGCTCAGAGGGACTCCCTGTTGTGGAAGCTCGCGGGGTCG59971-01 DNA SequenceTGCTGCGCGAGTCCCGTCATGTGGTCCTGTCTGGCTGTAGCACCCTGAGCCTGCTGACTCCCACACTGCAACAGCTGAACCACGTATTTGAGCTGCACCTGGGGCCATGGGGCCCTGGCCAGACAGGCTTTGTGGCTCTGCCCTCCCATCCTGCCGACTCCCCTGTTATTCTTCAGCTTCAGTTTCTCTTCGATGTGCTGCAGAAAACACTTTCACTCAAGCTGGTCCATGTTGCTGGTCCTGGCCCCACAGGGCCCATCAAGATTTTCCCCTTCAAATCCCTTCGGCACCTGGAGCTCCCAGGTGTTCCCCTCCACTGTCTCCATGGCCTCCCAGGCATCTACTCCCAGCTACAATGCACTGACCGCCTTAGACAGCTCCCTGCGCCTCTTGTCAGCTCTGCGTTTCTTGAACCTAAGCCACAATCAAGTCCAGGACTGTCAGGGATTCCTGATGGATTTGTGTGAGCTCCACCATCTGGACATCTCCTATAATCGCCTGCATTTGGTGCCAAGAATGGGACCCTCAGGGGCTGCTCTGGGGGTCCTGATACTGCGAGGCAATGAGCTTCGGAGCCTGCCAGGCCTAGAGCAGCTGAGGAATCTGCGGCACCTGGATTTGGCATACAACCTGCTGGAAGGACACCGGGAGCTGTCACCACTGTGGCTGCTGGCTGAGCTCCGCAAGCTCTACCTGGAGGGGAACCCTCTTTGGTTCCACCCTGAGCACCGAGCAGCCACTGCCCAGTACTTGTCACCCCGGGCCACCCATGCTGCTACTGGCTTCCTTCTCGATGGCAAGGTCTTGTCACTGACAGATTTTCAGCAGACTCACACATCCTTGCGGCTCAGCCCCATGGGCCCACCTTTGCCCTGGCCAGTGGGGAGTACTCCTGAAACCTCAGGTCGCCCTGACCTGAGTGACAGCCTCTCCTCAGGGGGTGTTGTGACCCAGCCCCTGCTTCATAAGGTTAAGAGCCGAGTCCGTGTGAGGCGGGCAAGCATCTCTGAACCCAGTGATACGGACCCGGAGCCCCGAACTCTGAACCCCTCTCCGGCTGGTTGGTTCGTGCAGCAGCACCCGGAGCTGGAGCTCATGAGCAGCTTCCGGGAACGGTTCGGCCGCAACTGGCTGCAGTACAGGAGTCACCTGGAGCCCTCCGGAAACCCTCTGCCGGCCACCCCCACTACTTCTGCACCCAGTGCACCTCCAGCCAGCTCCCAGGGCCCCGACACTGCACCCAGACCTTCACCCCCGCAGCAGGAAGCCAGAGGCCCCCAGGAGTCACCACAGAAAATGTCAGAGGAGGTCAGGGCGGAGCCACAGGAGGAGGAAGAGGAGAAGGAGGGGAAGGAGGAGAAGGAGGAGGGGGAGATGGTGGAACAGGGAGAAGAGGAGGCAGGAGAGGAGGAAGAAGAGGAGCAGGACCAGAAGGAAGTGGAAGCGGAACTCTGTCGCCCCTTGTTGGTGTGTCCCCTGGAGGGGCCTGAGGGCGTACGGGGCAGGGAATGCTTTCTCAGGGTCACTTCTGCCCACCTGTTTGAGGTGGAACTCCAAGCAGCTCGCACCTTGGAGCGACTGGAGCTCCAGAGTCTGGAGGCAGCTGAGATAGAGCCGGAGGCCCAGGCCCAGGGTCCCCCTCTTGCTCCGCAGGGCTCAGATCTGCTCCCTGGAGCCCCCATCCTCAGTCTGCGCTTCTCCTACATCTGCCCTGACCGGCAGTTGCGTCGCTATTTGGTGCTGGAGCCTGATGCCCACGCAGCTGTCCACCAGCTGCTTGCCGTGTTGACCCCAGTCACCAATGTGGCTCGGGAACAGCTTGGGGAGGCCAGGGACCTCCTGCTGGGTAGATTCCAGTCTCTACGCTGTGGCCATGAGTTCAAGCCAGAGGAGCCCAGCATCGGATTAGACAGTGAGGAAGGCTGGAGGCCTCTGTTCCAAAAGACAGAATCTCCTGCTGTGTGTCCTAACTAGTCGCATAGAGCTGGGCCTGGCAGCCCAGAGCCTGCGGCTAGAGTGGGCAGCTGGGGCGGGCCGCTGTGTGCTGCTGCCCCGACATGCCAGGCATTGCCGGGCCTTCCTAGAGCAGCTCCTTGGTGTCTTGCAGTCTCTCCCCCCTGCCTGGAGGAACTCTGTCAGTGCCACAGAGGAGGAGGTCACCCCCCAGCACCGGCTCTGGCCATTGCTGGAAAAAGACTCATCCTGCAGCTGATGCTTCCCTCCACCTGCCTCGTATCCCTGTTGCTGACTCCCTCCACCCTGTTCCTGTTAGATGAGGATGCTGCAGGGTCCCCGGCAGAGCCCTCTCCTCCAGCACCATCTGCCGAAGCCTCTGAGAAGGTGCCTCCCTCGGCGCCGCGCCCTGCTGTCCGTGTCAGGGAGCAGCAGCCACTCAGCAGCCTGAGCTCCGTGCTGCTCTACCGCTCAGCCCCTGAGGACTTGCGGCTGCTCTTCTACCATGAGGTGTCCCGGCTGGAGAGCTTTTCGGCACTCCGGAGCTGTTTTCCATCCGACTCCGCACACTCATCCAAGAGGCGCTCGCCCTTCACCGATGAGGGTCCCACGCTGACCTTGGCCCTGACCTCAGGAGCCACGCTORF start: ATG at 13ORF Stop: TGA at 3307SEQ ID NO:3541098 aaMW at 121004.1 kDNOV127a,MTTAQRDSLLWKLAGLLRESGDVVLSGCSTLSLLTPTLQQLNHVFELHLGPWGPGQTGCG59971-01 ProteinSequenceFVALPSHPADSPVILQLQFLFDVLQKTLSLKLVHVAGPGPTGPIKIFPFKSLRHLELRGVPLHCLHGLRGIYSQLETLICSRSLQALEELLSACGGDFCSALPWLALLSANFSYNALTALDSSLRLLSALRFLNLSHNQVQDCQGFLMDLCELHHLDISYNRLHLVPRMGPSGAALGVLILRGNELRSLPGLEQLRNLRHLDLAYNLLEGHRELSPLWLLAELRKLYLEGNPLWFHPEHRAATAQYLSPRARDAATGFLLDGKVLSLTDFQQTHTSLGLSPMGPPLPWPVGSTPETSGGPDLSDSLSSGGVVTQPLLHKVKSRVRVRRASISEPSDTDPEPRTLNPSPAGWFVQQHPELELMSSFRERFGRNWLQYRSHLEPSGNPLPATPTTSAPSAPPASSQGPDTAPRPSPPQEEARGPQESPQKMSEEVRAEPQEEEEEKEGKEEKEEGEMVEQGEEEAGEEEEEEQDQKEVEAELCRPLLVCPLEGPEGVRGRECFLRVTSAHLFEVELQAARTLERLELQSLEAAEIEPEAQAQGPPLATGSDLLPGAPILSLRFSYICPDRQLRRYLVLEPDAAHAAVQELLAVLTPVTNVAREQLGEARDLLLGRFQCLRCGHEFKPEEPRMGLDSEEGWRPLFQKTESPAVCPNCGSDHVVLLAVSRGTPNRERKQGEQSLAPSPSASPVCHPPGHGDHLDRAKNSPPQAPSTRDHGSWSLSPAPERCGLRSVDHRLRLFLDVEVFSDAQEEFQCCLKVPVALAGHTGEFMCLVVVSDRRLYLLKVTGEMSEPPASWLQLTLAVPLQDLSGIELGLAGQSLRLEWAAGAGRCVLLPRDARHCRAFLEELLGVLQSLPPAWRNCVSATEEEVTPQHRLWPLLEKDSSLEARQFFYLRAFLVEGEASVQLMLPSTCLVSLLLTPSTLFLLDEDAAGSPAEPSPPAASGEASEKVPPSGPGPAVRVREQQPLSSLSSVLLYRSAPEDLRLLFYDEVSRLESFWALRVVCQEQLTALLAWIREPWEELFSIGLRTVIQEALALDRSEQ ID NO:3553348 bpNOV127b,CGTCCCGTGGCCATGACGACCGCTCAGAGGGACTCCCTGTTGTGGAAGCTCGCGGGGTCG59971-02 DNA Sequence DNA SequenceTGCTGCGGGAGTCCGGTGATGTGGTCCTGTCTGGCTGTAGCACCCTGAGCCTGCTGACTCCCACACTGCAACAGCTGAACCACGTATTTGAGCTGCACCTGGGGCCATGGGGCCCTGGCCAGACAGGCTTTGTGGCTCTGCCCTCCCATCCTGCCGACTCCCCTGTTATTCTTCAGCTTCAGTTTCTCTTCGATGTGCTGCAGAAAACACTTTCACTCAAGCTGGTCCATGTTGCTGGTCCTGGCCCCACAGGGCCCATCAAGATTTTCCCCTTCAAATCCCTTCGGCACCTGGAGCTCCGAGGTGTTCCCCTCCACTGTCTGCATGGCCTCCGAGGCATCTACTCCCAGCTGGAGACCCTGATTTGCAGCAGGAGCCTCCAGGCATTAGACGAGCTCCTCTCAGCCTGCGGCGGCGACTTCTGCTCTGCCCTCCCTTGGCTGGCTCTGCTTTCTGCCAACTTCAGCTACAATGCACTGACCGCCTTAGACAGCTCCCTGCGCCTCTTGTCAGCTCTGCGTTTCTTGAACCTAAGCCACAATCAAGTCCAGGACTGTCAGGGATTCCTGATGGATTTCTGTGAGCTCCACCATCTGGACATCTCCTATAATCGCCTGCATTTGGTGCCAAGAATGGGACCCTCAGGGCCTGCTCTGGGGCTCCTGATACTGCGAGGCAATGAGCTTCGGAGCCTGCCAGGCCTAGAGCAGCTGAGGAATCTGCGGCACCTGGATTTGGCATACAACCTGCTGGAAGGACACCGGGAGCTGTCACCACTGTGGCTGCTGGCTGAGCTCCGCAAGCTCTACCTGGAGGGCAACCCTCTTTGGTTCCACCCTGAGCACCGAGCAGCCACTGCCCAGTACTTGTCACCCCGGGCCAGGGATGCTGCTACTGGCTTCCTTCTCGATGGCAAGGTCTTGTCACTGACAGATTTTCAGCAGACTCACACATCCTTGGGGCTCAGCCCCATGGGCCCACCTTTGAACCCCTCTCCGCCTCGTTGGTTCGTGCAGCAGCACCCGGAGCTGGAGCTCATGAGCAGCTTCCGGGAACGGTTCGGCCGCAACTGGCTGCAGTACAGGAGTCACCTGGAGCCCTCCGGAAACCCTCTGCCGGCCACCCCCACTACTTCTGCACCCAGTGCACCTCCAGCCAGCTCCCAGGGCCCCGACACTGCACCCAGACCTTCACCCCCGCAGGAGGAAGCCAGAGGCCCCCAGGAGTCACCACAGAAAATGTCAGAGGAGCTCAGGGCGGAGCCACAGGAGGAGGAAGACGAGAAGGAGGGGAAGGAGGAGAAGGAGGAGGGGGAGATGGTGGAACAGGGAGAAGAGGACGCAGGAGAGGAGGAAGAAGAGCAGCAGGACCAGAACGAAGTGGAACCGGAACTCTGTCGCCCCTTGTTGGTCTGTCCCCTGGAGGGGCCTGAGGGCGTACGGGGCAGGGAATGCTTTCTCAGGGTCACTTCTGCCCACCTGTTTGAGGTGGPACTCCAAGCAGCTCGCACCTTGGAGCGACTGGAGCTCCAGAGTCTGGAGGCACCTGAGATAGAGCCGGAGGCCCACGCCCAGAGGTCGCCCAGGCCCACGGGCTCAGATCTGCTCCCTGGAGCCCCCATGCTCAGTCTGCGCTTCTCCTACATCTGCCCTGACCGGCAGTTGCGTCGCTATTTGGTGCTGGAGCCTGATGCCCACGCAGCTCTCCAGGAGCTGCTTGCCGTGTTGACCCCAGTCACCAATCTGGCTCGGCAACAGCTTGCCGACCCCAGGGACCTCCTGCTGGGTAGATTCCAGTGTCTACGCTCTGCCCATGACTTCAAGCCAGAGGAGCCCAGGATGGGATTAGACAGTGAGGAAGGCTCGAGGCCTCTGTTCCAAAAGACAGAATCTCCTGCTGTGTGTCCTAACTGTGCTAGTCACCACGTGCTTCTCCTCCCTCTCTCTCGGGGAACCCCCAACAGCGACCCGAAACAGGCACAGCAGTCTCTGGCTCCTTCTCCGTCTGCCACCCCTCTCTGCCACCCTCCTGGCCATGCTCACCACCTTCACAGGGCCAACAACAGCCCACCTCACGCACCGACCACCCCTGACCATGGTAGTTGGAGCCTCAGTCCCGCCCGTGAGCGCTGTGGCCTCCGCTCTGTGGACCACCGACTCCGGCTCTTCCTGGATGTTGAGGTGTTCAGCGATGCCCACGAGGAGTTCCAGTGCTGCCTCAAGGTCCCACTCCCATTGGCAGGCCACACTGGGGAGTTCATGTGCCTTCTGCTTGTGTCTGACCGCAGCCTCTACCTGTTGAAGGTGACTGGGGAGATGACTGACCCTCCAGCTACCTGGCTGCAGCTGACCCTGGCTCTTCCCCTCCAGGATCTGAGTGGCATACAGCTGGGCCTGGCAGGCCACAGCCTGCGGCTAGAGTGGGCAGCTCGGGCGGGCCGCTGTGTGCTCCTGCCCCGACATCCCAGCCATTGCCGGGCCTTCCTAGACGACCTCCTTGGTGTCTTGCAGTCTCTGCCCCCTCCCTGCAGGAACTGTGTCACTGCCACAGAGGAGGAGGTCACCCCCCACCACCGGCTCTGGCCATTCCTGGAAAAACACTCATCCTTGCAGGCTCCCCAGTTCTTCTACCTTCCGGCGTTCCTGGTTGAACCTGAAGCCTCTCTCCAGCTGATGCTTCCCTCCACCTGCCTCGTATCCCTGTTGCTGACTCCGTCCACCCTGTTCCTGTTAGATGAGGATGCTGCAGGGTCCCCGGCACAGCCCTCTCCTCCAGCAGCATCTGGCGAACCCTCTGAGAAGGTGCCTCCCTCGGGGCCCCGCCCTGCTGTGCGTGTCAGCCAGCAGCACCCACTCAGCAGCCTGAGCTCCGTGCTGCTCTACCGCTCAGCCCCTGAGGACTTGCGGCTGCTCTTCTACGATGAGGTGTCCCGGCTGGAGAGCTTTTGGGCACTCCGTGTGGTGTGTCAGGAGCAGCTGACAGCCCTGCTTGCCTGGATCCGGGAACCATGGGAGGAGCTGTTTTCCATCGGACTCCGGACAGTGATCCAAGAGGCGCTGGCCCTTGACCGATGAGGGTCCCACGCTGACCTTGGCCCTGACCTCAGGAGCCACGCTORF Start: ATG at 13ORF Stop: TGA at 3304SEQ ID NO:3561097 aaMW at 121064.1 kDNOV127b,MTTAQRDSLLWKLAGLLRESGDVVLSGCSTLSLLTPTLQQLNHVFELHLGPWGPGQTGCG59971-02 ProteinSequenceFVALPSHPADSPVILQLQFLFDVLQKTLSLKLVHVAGPGPTGPIKIFPFKSLRHLELRGVPLHCLHGLRGIYSQLETLICSRSLQALEELLSACGGDFCSALPWLALLSANFSYNALTALDSSLRLLSALRFLNLSHNQVQDCQGFLMDLCELHHLDISYNRLHLVPRMGPSGAALGVLILRGNELRSLPGLEQLRNLRHLDLAYNLLEGHRELSPLWLLAELRKLYLEGNPLWFHPEHRAATAQYLSPRARDAATGFLLDGKVLSLTDFQQTHTSLGLSPMGPPLPWPVGSTPETSGGPDLSDSLSSGGVVTQPLLHKVKSRVRVRRASISEPSDTDPEPRTLNPSPAGWFVQQHPELELMSSFRERFGRNWLQYRSHLEPSGNPLPATPTTSAPSAPPASSQGPDTAPRPSPPQEEARGPQESPQKMSEEVRAEPQEEEEEKEGKEEKEEGEMVEQGEEEAGEEEEEEQDQKEVEAELCRPLLVCPLEGPEGVRGRECFLRVTSAHLFEVELQAARTLERLELQSLEAAEIEPEAQAQGPPLATGSDLLPGAPILSLRFSYICPDRQLRRYLVLEPDAHAAVQELLAVLTPVTNVAREQLGEARDLLLGRFQCLRCGHEFKPEEPRMGLDSEEGWRPLFQKTESPAVCPNCGSDHVVLLAVSRGTPNRERKQGEQSLAPSPSASPVCHPPGHGDHLDRAKNSPPQAPSTRDHGSWSLSPAPERCGLRSVDHRLRLFLDVEVFSDAQEEFQCCLKVPVALAGHTGEFMCLVVVSDRRLYLLKVTGEMSEPPASWLQLTLAVPLQDLSGIELGLAGQSLRLEWAAGAGRCVLLPRDARHCRAFLEELLGVLQSLPPAWRNCVSATEEEVTPQHRLWPLLEKDSSLEARQFFYLRAFLVEGEASVQLMLPSTCLVSLLLTPSTLFLLDEDAAGSPAEPSPPAASGEASEKVPPSGPGPAVRVREQQPLSSLSSVLLYRSAPEDLRLLFYDEVSRLESFWALRVVCQEQLTALLAWIREPWEELFSIGLRTVIQEALALDR


[0990] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 127B.
666TABLE 127BComparison of NOV127a against NOV127b.Identities/SimilaritiesProteinNOV127a Residues/for theSequenceMatch ResiduesMatched RegionNOV127b1 . . . 1098891/1098 (81%)1 . . . 1097891/1098 (81%)


[0991] Further analysis of the NOV127a protein yielded the following properties shown in Table 127C.
667TABLE 127CProtein Sequence Properties NOV127aPSort0.5163 probability located in mitochondrial matrix space;analysis:0.3000 probability located in microbody (peroxisome); 0.2442probability located in mitochondrial inner membrane; 0.2442probability located in mitochondrial intermembrane spaceSignalPNo Known Signal Sequence Predictedanalysis:


[0992] A search of the NOV127a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 127D.
668TABLE 127DGeneseq Results for NOV127aNOV127aIdentities/Residues/SimilaritiesGeneseqProtein/Organism/LengthMatchfor theExpectIdentifier[Patent #, Date]ResiduesMatched RegionValueAAM39827Human polypeptide SEQ ID NO375 . . . 528140/154(90%)3e−782972 - Homo sapiens, 169 aa. 14 . . . 167145/154(93%)[WO200153312-A1, 26 JUL 2001]AAM41613Human polypeptide SEQ ID NO375 . . . 528140/154(90%)4e−786544 - Homo sapiens, 184 aa. 29 . . . 182145/154(93%)[WO200153312-A1, 26 JUL 2001]AAU19764Human novel extracellular matrix444 . . . 647157/207(75%)2e−75protein, Seq ID No 414 - Homo 13 . . . 209160/207(76%)sapiens, 211 aa. [WO200155368-A1, 2 AUG 2001]ABB19833Protein #1832 encoded by probe409 . . . 535127/127(100%)2e−70for measuring heart cell gene 1 . . . 127127/127(100%)expression - Homo sapiens, 127 aa.[WO200157274-A2, 9 AUG2001]AAM67606Human bone marrow expressed409 . . . 535127/127(100%)2e−70probe encoded protein SEQ ID 1 . . . 127127/127(100%)NO: 27912 - Homo sapiens, 127aa. [WO200157276-A2, 9 AUG2001]


[0993] In a BLAST search of public sequence databases, the NOV127a protein was found to have homology to the proteins shown in the BLASTP data in Table 127E.
669TABLE 127EPublic BLASTP Results for NOV127aNOV127aIdentities/ProteinResidues/SimilaritiesAccessionMatchfor theExpectNumberProtein/Organism/LengthResiduesMatched PortionValueAAL49726LKB1-INTERACTING  1 . . . 10981077/1098(98%)0.0PROTEIN 1 - Homo sapiens 12 . . . 10991078/1098(98%)(Human), 1099 aa.Q96PY9KIAA1898 PROTEIN - Homo 76 . . . 10981003/1023(98%)0.0sapiens (Human), 1013 aa  1 . . . 10131003/1023(98%)(fragment).Q96CN3SIMILAR TO RIKEN CDNA 288 . . . 1098793/811(97%)0.01200014D22 GENE - Homo 4 . . . 804793/811(97%)sapiens (Human), 804 aa(fragment).Q9DBT71200014D22RIK PROTEIN -   1 . . . 1098816/1098(74%)0.0Mus musculus (Mouse), 1072 aa.  1 . . . 1072895/1098(81%)Q9VMK9CG9044 PROTEIN - Drosophila 12 . . . 433139/459(30%)6e−38melanogaster (Fruit fly), 1289 aa. 8 . . . 463220/459(47%)


[0994] PFam analysis predicts that the NOV127a protein contains the domains shown in the Table 127F.
670TABLE 127FDomain Analysis of NOV127aIdentities/SimilaritiesPfamNOV127afor theExpectDomainMatch RegionMatched RegionValueLRR: domain 1 of 5164 . . . 1867/25(28%)2.5e+0215/25(60%)LRR: domain 2 of 5187 . . . 2096/25(24%)2.5e+0216/25(64%)LRR: domain 3 of 5210 . . . 2318/25(32%)8313/25(52%)LRR: domain 4 of 5233 . . . 2549/25(36%)1617/25(68%)LRR: domain 5 of 5255 . . . 27910/27(37%)2219/27(70%)Pkinase_C:620 . . . 6295/11(45%)8.9domain 1 of 19/11(82%)rubredoxin:669 . . . 6865/18(28%)4.6domain 1 of 213/18(72%)rubredoxin:708 . . . 7135/6(83%)1.2e+03domain 2 of 26/6(100%)



Example B


Sequencing Methodology and Identofication of NOVX Clones

[0995] 1. GeneCalling™ Technology: This is a proprietary method of performing differential gene expression profiling between two or more samples developed at CuraGen and described by Shimkets, et al., “Gene expression analysis by transcript profiling coupled to a gene database query” Nature Biotechnology 17:198-803 (1999). cDNA was derived from various human samples representing multiple tissue types, normal and diseased states, physiological states, and developmental states from different donors. Samples were obtained as whole tissue, primary cells or tissue cultured primary cells or cell lines. Cells and cell lines may have been treated with biological or chemical agents that regulate gene expression, for example, growth factors, chemokines or steroids. The cDNA thus derived was then digested with up to as many as 120 pairs of restriction enzymes and pairs of linker-adaptors specific for each pair of restriction enzymes were ligated to the appropriate end. The restriction digestion generates a mixture of unique cDNA gene fragments. Limited PCR amplification is performed with primers homologous to the linker adapter sequence where one primer is biotinylated and the other is fluorescently labeled. The doubly labeled material is isolated and the fluorescently labeled single strand is resolved by capillary gel electrophoresis. A computer algorithm compares the electropherograms from an experimental and control group for each of the restriction digestions. This and additional sequence-derived information is used to predict the identity of each differentially expressed gene fragment using a variety of genetic databases. The identity of the gene fragment is confirmed by additional, gene-specific competitive PCR or by isolation and sequencing of the gene fragment.


[0996] 2. SeqCalling™ Technology: cDNA was derived from various human samples representing multiple tissue types, normal and diseased states, physiological states, and developmental states from different donors. Samples were obtained as whole tissue, primary cells or tissue cultured primary cells or cell lines. Cells and cell lines may have been treated with biological or chemical agents that regulate gene expression, for example, growth factors, chemokines or steroids. The cDNA thus derived was then sequenced using CuraGen's proprietary SeqCalling technology. Sequence traces were evaluated manually and edited for corrections if appropriate. cDNA sequences from all samples were assembled together, sometimes including public human sequences, using bioinformatic programs to produce a consensus sequence for each assembly. Each assembly is included in CuraGen Corporation's database. Sequences were included as components for assembly when the extent of identity with another component was at least 95% over 50 bp. Each assembly represents a gene or portion thereof and includes information on variants, such as splice forms single nucleotide polymorphisms (SNPs), insertions, deletions and other sequence variations.


[0997] 3. PathCalling™ Technology:


[0998] The NOVX nucleic acid sequences are derived by laboratory screening of cDNA library by the two-hybrid approach. cDNA fragments covering either the full length of the DNA sequence, or part of the sequence, or both, are sequenced. In silico prediction was based on sequences available in CuraGen Corporation's proprietary sequence databases or in the public human sequence databases, and provided either the full length DNA sequence, or some portion thereof.


[0999] The laboratory screening was performed using the methods summarized below:


[1000] cDNA libraries were derived from various human samples representing multiple tissue types, normal and diseased states, physiological states, and developmental states from different donors. Samples were obtained as whole tissue, primary cells or tissue cultured primary cells or cell lines. Cells and cell lines may have been treated with biological or chemical agents that regulate gene expression, for example, growth factors, chemokines or steroids. The cDNA thus derived was then directionally cloned into the appropriate two-hybrid vector (Gal4-activation domain (Gal4-AD) fusion). Such cDNA libraries as well as commercially available cDNA libraries from Clontech (Palo Alto, Calif.) were then transferred from E. coli into a CuraGen Corporation proprietary yeast strain (disclosed in U.S. Pat. Nos. 6,057,101 and 6,083,693, incorporated herein by reference in their entireties).


[1001] Gal4-binding domain (Gal4-BD) fusions of a CuraGen Corportion proprietary library of human sequences was used to screen multiple Gal4-AD fusion cDNA libraries resulting in the selection of yeast hybrid diploids in each of which the Gal4-AD fusion contains an individual cDNA. Each sample was amplified using the polymerase chain reaction (PCR) using non-specific primers at the cDNA insert boundaries. Such PCR product was sequenced; sequence traces were evaluated manually and edited for corrections if appropriate. cDNA sequences from all samples were assembled together, sometimes including public human sequences, using bioinformatic programs to produce a consensus sequence for each assembly. Each assembly is included in CuraGen Corporation's database. Sequences were included as components for assembly when the extent of identity with another component was at least 95% over 50 bp. Each assembly represents a gene or portion thereof and includes information on variants, such as splice forms single nucleotide polymorphisms (SNPs), insertions, deletions and other sequence variations.


[1002] Physical clone: the cDNA fragment derived by the screening procedure, covering the entire open reading frame is, as a recombinant DNA, cloned into pACT2 plasmid (Clontech) used to make the cDNA library. The recombinant plasmid is inserted into the host and selected by the yeast hybrid diploid generated during the screening procedure by the mating of both CuraGen Corporation proprietary yeast strains N106′ and YULH (U.S. Pat. Nos. 6,057,101 and 6,083,693).


[1003] 4. RACE: Techniques based on the polymerase chain reaction such as rapid amplification of cDNA ends (RACE), were used to isolate or complete the predicted sequence of the cDNA of the invention. Usually multiple clones were sequenced from one or more human samples to derive the sequences for fragments. Various human tissue samples from different donors were used for the RACE reaction. The sequences derived from these procedures were included in the SeqCalling Assembly process described in preceding paragraphs.


[1004] 5. Exon Linking: The NOVX target sequences identified in the present invention were subjected to the exon linking process to confirm the sequence. PCR primers were designed by starting at the most upstream sequence available, for the forward primer, and at the most downstream sequence available for the reverse primer. Table B1 shows the sequences of the PCR primers used for obtaining different clones. In each case, the sequence was examined, walking inward from the respective termini toward the coding sequence, until a suitable sequence that is either unique or highly selective was encountered, or, in the case of the reverse primer, until the stop codon was reached. Such primers were designed based on in silico predictions for the full length cDNA, part (one or more exons) of the DNA or protein sequence of the target sequence, or by translated homology of the predicted exons to closely related human sequences from other species. These primers were then employed in PCR amplification based on the following pool of human cDNAs: adrenal gland, bone marrow, brain—amygdala, brain—cerebellum, brain—hippocampus, brain—substantia nigra, brain—thalamus, brain—whole, fetal brain, fetal kidney, fetal liver, fetal lung, heart, kidney, lymphoma—Raji, mammary gland, pancreas, pituitary gland, placenta, prostate, salivary gland, skeletal muscle, small intestine, spinal cord, spleen, stomach, testis, thyroid, trachea, uterus. Usually the resulting amplicons were gel purified, cloned and sequenced to high redundancy. The PCR product derived from exon linking was cloned into the pCR2.1 vector from Invitrogen. The resulting bacterial clone has an insert covering the entire open reading frame cloned into the pCR2.1 vector. The resulting sequences from all clones were assembled with themselves, with other fragments in CuraGen Corporation's database and with public ESTs. Fragments and ESTs were included as components for an assembly when the extent of their identity with another component of the assembly was at least 95% over 50 bp. In addition, sequence traces were evaluated manually and edited for corrections if appropriate. These procedures provide the sequence reported herein.


[1005] 6. Physical Clone:


[1006] Exons were predicted by homology and the intron/exon boundaries were determined using standard genetic rules. Exons were further selected and refined by means of similarity determination using multiple BLAST (for example, tBlastN, BlastX, and BlastN) searches, and, in some instances, GeneScan and Grail. Expressed sequences from both public and proprietary databases were also added when available to further define and complete the gene sequence. The DNA sequence was then manually corrected for apparent inconsistencies thereby obtaining the sequences encoding the full-length protein.


[1007] The PCR product derived by exon linking, covering the entire open reading frame, was cloned into the pCR2.1 vector from Invitrogen to provide clones used for expression and screening purposes.



Example C


Quantitative Expression Analysis of Clones in Various Cells and Tissues

[1008] The quantitative expression of various clones was assessed using microtiter plates containing RNA samples from a variety of normal and pathology-derived cells, cell lines and tissues using real time quantitative PCR (RTQ PCR). RTQ PCR was performed on an Applied Biosystems ABI PRISM® 7700 or an ABI PRISM® 7900 HT Sequence Detection System. Various collections of samples are assembled on the plates, and referred to as Panel 1 (containing normal tissues and cancer cell lines), Panel 2 (containing samples derived from tissues from normal and cancer sources), Panel 3 (containing cancer cell lines), Panel 4 (containing cells and cell lines from normal tissues and cells related to inflammatory conditions), Panel 5D/5I (containing human tissues and cell lines with an emphasis on metabolic diseases), AI_comprehensive_panel (containing normal tissue and samples from autoimmune diseases), Panel CNSD.01 (containing central nervous system samples from normal and diseased brains) and CNS_neurodegeneration_panel (containing samples from normal and Alzheimer's diseased brains).


[1009] RNA integrity from all samples is controlled for quality by visual assessment of agarose gel electropherograms using 28S and 18S ribosomal RNA staining intensity ratio as a guide (2:1 to 2.5:1 28s:18s) and the absence of low molecular weight RNAs that would be indicative of degradation products. Samples are controlled against genomic DNA contamination by RTQ PCR reactions run in the absence of reverse transcriptase using probe and primer sets designed to amplify across the span of a single exon.


[1010] First, the RNA samples were normalized to reference nucleic acids such as constitutively expressed genes (for example, β-actin and GAPDH). Normalized RNA (5 ul) was converted to cDNA and analyzed by RTQ-PCR using One Step RT-PCR Master Mix Reagents (Applied Biosystems; Catalog No. 4309169) and gene-specific primers according to the manufacturer's instructions.


[1011] In other cases, non-normalized RNA samples were converted to single strand cDNA (sscDNA) using Superscript II (Invitrogen Corporation; Catalog No. 18064-147) and random hexamers according to the manufacturer's instructions. Reactions containing up to 10 μg of total RNA were performed in a volume of 20 μl and incubated for 60 minutes at 42° C. This reaction can be scaled up to 50 μg of total RNA in a final volume of 100 μl. sscDNA samples are then normalized to reference nucleic acids as described previously, using 1×TaqMan® Universal Master mix (Applied Biosystems; catalog No. 4324020), following the manufacturer's instructions.


[1012] Probes and primers were designed for each assay according to Applied Biosystems Primer Express Software package (version I for Apple Computer's Macintosh Power PC) or a similar algorithm using the target sequence as input. Default settings were used for reaction conditions and the following parameters were set before selecting primers: primer concentration=250 nM, primer melting temperature (Tm) range=58°-60° C., primer optimal Tm=59° C., maximum primer difference=2° C., probe does not have 5′G, probe Tm must be 10° C. greater than primer Tm, amplicon size 75 bp to 100 bp. The probes and primers selected (see below) were synthesized by Synthegen (Houston, Tex., USA). Probes were double purified by HPLC to remove uncoupled dye and evaluated by mass spectroscopy to verify coupling of reporter and quencher dyes to the 5′ and 3′ ends of the probe, respectively. Their final concentrations were: forward and reverse primers, 900 nM each, and probe, 200 nM.


[1013] PCR conditions: When working with RNA samples, normalized RNA from each tissue and each cell line was spotted in each well of either a 96 well or a 384-well PCR plate (Applied Biosystems). PCR cocktails included either a single gene specific probe and primers set, or two multiplexed probe and primers sets (a set specific for the target clone and another gene-specific set multiplexed with the target probe). PCR reactions were set up using TaqMan® One-Step RT-PCR Master Mix (Applied Biosystems, Catalog No. 4313803) following manufacturer's instructions. Reverse transcription was performed at 48° C. for 30 minutes followed by amplification/PCR cycles as follows: 95° C. 10 min, then 40 cycles of 95° C. for 15 seconds, 60° C. for 1 minute. Results were recorded as CT values (cycle at which a given sample crosses a threshold level of fluorescence) using a log scale, with the difference in RNA concentration between a given sample and the sample with the lowest CT value being represented as 2 to the power of delta CT. The percent relative expression is then obtained by taking the reciprocal of this RNA difference and multiplying by 100.


[1014] When working with sscDNA samples, normalized sscDNA was used as described previously for RNA samples. PCR reactions containing one or two sets of probe and primers were set up as described previously, using 1×TaqMan® Universal Master mix (Applied Biosystems; catalog No. 4324020), following the manufacturer's instructions. PCR amplification was performed as follows: 95° C. 10 min, then 40 cycles of 95° C. for 15 seconds, 60° C. for 1 minute. Results were analyzed and processed as described previously.


[1015] Panels 1, 1.1, 1.2, and 1.3D


[1016] The plates for Panels 1, 1.1, 1.2 and 1.3D include 2 control wells (genomic DNA control and chemistry control) and 94 wells containing cDNA from various samples. The samples in these panels are broken into 2 classes: samples derived from cultured cell lines and samples derived from primary normal tissues. The cell lines are derived from cancers of the following types: lung cancer, breast cancer, melanoma, colon cancer, prostate cancer, CNS cancer, squamous cell carcinoma, ovarian cancer, liver cancer, renal cancer, gastric cancer and pancreatic cancer. Cell lines used in these panels are widely available through the American Type Culture Collection (ATCC), a repository for cultured cell lines, and were cultured using the conditions recommended by the ATCC. The normal tissues found on these panels are comprised of samples derived from all major organ systems from single adult individuals or fetuses. These samples are derived from the following organs: adult skeletal muscle, fetal skeletal muscle, adult heart, fetal heart, adult kidney, fetal kidney, adult liver, fetal liver, adult lung, fetal lung, various regions of the brain, the spleen, bone marrow, lymph node, pancreas, salivary gland, pituitary gland, adrenal gland, spinal cord, thymus, stomach, small intestine, colon, bladder, trachea, breast, ovary, uterus, placenta, prostate, testis and adipose.


[1017] In the results for Panels 1, 1.1, 1.2 and 1.3D, the following abbreviations are used:


[1018] ca.=carcinoma,


[1019] *=established from metastasis,


[1020] met=metastasis,


[1021] s cell var=small cell variant,


[1022] non-s=non-sm=non-small,


[1023] squam=squamous,


[1024] pl. eff=pl effusion=pleural effusion,


[1025] glio=glioma,


[1026] astro=astrocytoma, and


[1027] neuro=neuroblastoma.


[1028] General_screening_panel_v0.4


[1029] The plates for Panel 1.4 include 2 control wells (genomic DNA control and chemistry control) and 94 wells containing cDNA from various samples. The samples in Panel 1.4 are broken into 2 classes: samples derived from cultured cell lines and samples derived from primary normal tissues. The cell lines are derived from cancers of the following types: lung cancer, breast cancer, melanoma, colon cancer, prostate cancer, CNS cancer, squamous cell carcinoma, ovarian cancer, liver cancer, renal cancer, gastric cancer and pancreatic cancer. Cell lines used in Panel 1.4 are widely available through the American Type Culture Collection (ATCC), a repository for cultured cell lines, and were cultured using the conditions recommended by the ATCC. The normal tissues found on Panel 1.4 are comprised of pools of samples derived from all major organ systems from 2 to 5 different adult individuals or fetuses. These samples are derived from the following organs: adult skeletal muscle, fetal skeletal muscle, adult heart, fetal heart, adult kidney, fetal kidney, adult liver, fetal liver, adult lung, fetal lung, various regions of the brain, the spleen, bone marrow, lymph node, pancreas, salivary gland, pituitary gland, adrenal gland, spinal cord, thymus, stomach, small intestine, colon, bladder, trachea, breast, ovary, uterus, placenta, prostate, testis and adipose. Abbreviations are as described for Panels 1, 1.1, 1.2, and 1.31).


[1030] Panels 2D and 2.2


[1031] The plates for Panels 2D and 2.2 generally include 2 control wells and 94 test samples; composed of RNA or cDNA isolated from human tissue procured by surgeons working in close cooperation with the National Cancer Institute's Cooperative Human Tissue Network (CHTN) or the National Disease Research Initiative (NDRI). The tissues are derived from human malignancies and in cases where indicated many malignant tissues have “matched margins” obtained from noncancerous tissue just adjacent to the tumor. These are termed normal adjacent tissues and are denoted “NAT” in the results below. The tumor tissue and the “matched margins” are evaluated by two independent pathologists (the surgical pathologists and again by a pathologist at NDRI or CHTN). This analysis provides a gross histopathological assessment of tumor differentiation grade. Moreover, most samples include the original surgical pathology report that provides information regarding the clinical stage of the patient. These matched margins are taken from the tissue surrounding (i.e. immediately proximal) to the zone of surgery (designated “NAT”, for normal adjacent tissue, in Table RR). In addition, RNA and cDNA samples were obtained from various human tissues derived from autopsies performed on elderly people or sudden death victims (accidents, etc.). These tissues were ascertained to be free of disease and were purchased from various commercial sources such as Clontech (Palo Alto, Calif.), Research Genetics, and Invitrogen.


[1032] Panel 3D


[1033] The plates of Panel 3D are comprised of 94 cDNA samples and two control samples. Specifically, 92 of these samples are derived from cultured human cancer cell lines, 2 samples of human primary cerebellar tissue and 2 controls. The human cell lines are generally obtained from ATCC (American Type Culture Collection), NCI or the German tumor cell bank and fall into the following tissue groups: Squamous cell carcinoma of the tongue, breast cancer, prostate cancer, melanoma, epidermoid carcinoma, sarcomas, bladder carcinomas, pancreatic cancers, kidney cancers, leukemias/lymphomas, ovarian/uterine/cervical, gastric, colon, lung and CNS cancer cell lines. In addition, there are two independent samples of cerebellum. These cells are all cultured under standard recommended conditions and RNA extracted using the standard procedures. The cell lines in panel 3D and 1.3D are of the most common cell lines used in the scientific literature.


[1034] Panels 4D, 4R, and 4.1D


[1035] Panel 4 includes samples on a 96 well plate (2 control wells, 94 test samples) composed of RNA (Panel 4R) or cDNA (Panels 4D/4.1D) isolated from various human cell lines or tissues related to inflammatory conditions. Total RNA from control normal tissues such as colon and lung (Stratagene, La Jolla, Calif.) and thymus and kidney (Clontech) was employed. Total RNA from liver tissue from cirrhosis patients and kidney from lupus patients was obtained from BioChain (Biochain Institute, Inc., Hayward, Calif.). Intestinal tissue for RNA preparation from patients diagnosed as having Crohn's disease and ulcerative colitis was obtained from the National Disease Research Interchange (NDRI) (Philadelphia, Pa.).


[1036] Astrocytes, lung fibroblasts, dermal fibroblasts, coronary artery smooth muscle cells, small airway epithelium, bronchial epithelium, microvascular dermal endothelial cells, microvascular lung endothelial cells, human pulmonary aortic endothelial cells, human umbilical vein endothelial cells were all purchased from Clonetics (Walkersville, Md.) and grown in the media supplied for these cell types by Clonetics. These primary cell types were activated with various cytokines or combinations of cytokines for 6 and/or 12-14 hours, as indicated. The following cytokines were used; IL-1 beta at approximately 1-5 ng/ml, TNF alpha at approximately 5-10 ng/ml, IFN gamma at approximately 20-50 ng/ml, IL-4 at approximately 5-10 ng/ml, IL-9 at approximately 5-10 ng/ml, IL-13 at approximately 5-10 ng/ml. Endothelial cells were sometimes starved for various times by culture in the basal media from Clonetics with 0.1% serum.


[1037] Mononuclear cells were prepared from blood of employees at CuraGen Corporation, using Ficoll. LAK cells were prepared from these cells by culture in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco/Life Technologies, Rockville, Md.), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), and 10 mM Hepes (Gibco) and Interleukin 2 for 4-6 days. Cells were then either activated with 10-20 ng/ml PMA and 1-2 μg/ml ionomycin, IL-12 at 5-10 ng/ml, IFN gamma at 20-50 ng/ml and IL-18 at 5-10 ng/ml for 6 hours. In some cases, mononuclear cells were cultured for 4-5 days in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), and 10 mM Hepes (Gibco) with PEA (phytohemagglutinin) or PWM (pokeweed mitogen) at approximately 5 μg/ml. Samples were taken at 24, 48 and 72 hours for RNA preparation. MLR (mixed lymphocyte reaction) samples were obtained by taking blood from two donors, isolating the mononuclear cells using Ficoll and mixing the isolated mononuclear cells 1:1 at a final concentration of approximately 2×106cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol (5.5×10−5M) (Gibco), and 10 mM Hepes (Gibco). The MLR was cultured and samples taken at various time points ranging from 1-7 days for RNA preparation.


[1038] Monocytes were isolated from mononuclear cells using CD14 Miltenyi Beads, +ve VS selection columns and a Vario Magnet according to the manufacturer's instructions. Monocytes were differentiated into dendritic cells by culture in DMEM 5% fetal calf serum (FCS) (Hyclone, Logan, Utah), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), and 10 mM Hepes (Gibco), 50 ng/ml GMCSFs and 5 ng/ml IL-4 for 5-7 days. Macrophages were prepared by culture of monocytes for 5-7 days in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), 10 mM Hepes (Gibco) and 10% AB Human Serum or MCSF at approximately 50 ng/ml. Monocytes, macrophages and dendritic cells were stimulated for 6 and 12-14 hours with lipopolysaccharide (LPS) at 100 ng/ml. Dendritic cells were also stimulated with anti-CD40 monoclonal antibody (Pharmingen) at 10 μg/ml for 6 and 12-14 hours.


[1039] CD4 lymphocytes, CD8 lymphocytes and NK cells were also isolated from mononuclear cells using CD4, CD8 and CD56 Miltenyi beads, positive VS selection column!; and a Vario Magnet according to the manufacturer's instructions. CD45RA and CD45RO CD4 lymphocytes were isolated by depleting mononuclear cells of CD8, CD56, CD14 and CD19 cells using CD8, CD56, CD14 and CD19 Miltenyi beads and positive selection. CD45RO beads were then used to isolate the CD45RO CD4 lymphocytes with the remaining cells being CD45RA CD4 lymphocytes. CD45RA CD4, CD45RO CD4 and CD8 lymphocytes were placed in DMBM 5% FCS (Hyclone), 100AM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), and 10 mM Hepes (Gibco) and plated at 106cells/ml onto Falcon 6 well tissue culture plates that had been coated overnight with 0.5 ug/ml anti-CD28 (Pharmingen) and 3 ug/ml anti-CD3 (OKT3, ATCC) in PBS. After 6 and 24 hours, the cells were harvested for RNA preparation. To prepare chronically activated CD8 lymphocytes, we activated the isolated CD8 lymphocytes for 4 days on anti-CD28 and anti-CD3 coated plates and then harvested the cells and expanded them in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×105M (Gibco), and 10 mM Hepes (Gibco) and IL-2. The expanded CD8 cells were then activated again with plate bound anti-CD3 and anti-CD28 for 4 days and expanded as before. RNA was isolated 6 and 24 hours after the second activation and after 4 days of the second expansion culture. The isolated NK cells were cultured in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), and 10 mM Hepes (Gibco) and IL-2 for 4-6 days before RNA was prepared.


[1040] To obtain B cells, tonsils were procured from NDRI. The tonsil was cut up with sterile dissecting scissors and then passed through a sieve. Tonsil cells were then spun down and resupended at 106cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), and 10 mM Hepes (Gibco). To activate the cells, we used PWM at 5 μg/ml or anti-CD40 (Pharmingen) at approximately 10 μg/ml and IL-4 at 5-10 ng/ml. Cells were harvested for RNA preparation at 24, 48 and 72 hours.


[1041] To prepare the primary and secondary Th1/Th2 and Tr1 cells, six-well Falcon plates were coated overnight with 101 g/ml anti-CD28 (Pharmingen) and 2 μg/ml OKT3 (ATCC), and then washed twice with PBS. Umbilical cord blood CD4 lymphocytes (Poietic Systems, German Town, Md.) were cultured at 105-106cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), 10 mM Hepes (Gibco) and IL-2 (4 ng/ml). IL-12 (5 ng/ml) and anti-IL4 (1 μg/ml) were used to direct to Th1, while IL-4 (5 ng/ml) and anti-IFN gamma (1 μg/ml) were used to direct to Th2 and IL-10 at 5 ng/ml was used to direct to Tr1. After 4-5 days, the activated Th1, Th2 and Tr1 lymphocytes were washed once in DMEM and expanded for 4-7 days in DMEM 5% FCS (Hyclone), 1001M non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), 10 mM Hepes (Gibco) and IL-2 (1 ng/ml). Following this, the activated Th1, Th2 and Tr1 lymphocytes were re-stimulated for 5 days with anti-CD28/OKT3 and cytokines as described above, but with the addition of anti-CD95L (11 g/ml) to prevent apoptosis. After 4-5 days, the Th1, Th2 and Tr1 lymphocytes were washed and then expanded again with IL-2 for 4-7 days. Activated Th1 and Th2 lymphocytes were maintained in this way for a maximum of three cycles. RNA was prepared from primary and secondary Th1, Th2 and Tr1 after 6 and 24 hours following the second and third activations with plate bound anti-CD3 and anti-CD28 mAbs and 4 days into the second and third expansion cultures in Interleukin 2.


[1042] The following leukocyte cells lines were obtained from the ATCC: Ramos, EOL-1, KU-812. EOL cells were further differentiated by culture in 0.1 mM dbcAMP at 5×105cells/ml for 8 days, changing the media every 3 days and adjusting the cell concentration to 5×105cells/ml. For the culture of these cells, we used DMEM or RPMI (as recommended by the ATCC), with the addition of 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), 10 mM Hepes (Gibco). RNA was either prepared from resting cells or cells activated with PMA at 10 ng/ml and ionomycin at 1 μg/ml for 6 and 14 hours. Keratinocyte line CCD106 and an airway epithelial tumor line NCI-H292 were also obtained from the ATCC. Both were cultured in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), and 10 mM Hepes (Gibco). CCD1106 cells were activated for 6 and 14 hours with approximately 5 ng/ml TNF alpha and 1 ng/ml IL-1 beta, while NCI-H292 cells were activated for 6 and 14 hours with the following cytokines: 5 ng/ml IL-4, 5 ng/ml IL-9, 5 ng/ml IL-13 and 25 ng/ml IFN gamma.


[1043] For these cell lines and blood cells, RNA was prepared by lysing approximately 107cells/ml using Trizol (Gibco BRL). Briefly, {fraction (1/10)} volume of bromochloropropane (Molecular Research Corporation) was added to the RNA sample, vortexed and after 10 minutes at room temperature, the tubes were spun at 14,000 rpm in a Sorvall SS34 rotor. The aqueous phase was removed and placed in a 15 ml Falcon Tube. An equal volume of isopropanol was added and left at −20° C. overnight. The precipitated RNA was spun down at 9,000 rpm for 15 min in a Sorvall SS34 rotor and washed in 70% ethanol. The pellet was redissolved in 300 μl of RNAse-free water and 35 μl buffer (Promega) 5 μl DTT, 7 μl RNAsin and 8 μl DNAse were added. The tube was incubated at 37° C. for 30 minutes to remove contaminating genomic DNA, extracted once with phenol chloroform and re-precipitated with {fraction (1/10)} volume of 3M sodium acetate and 2 volumes of 100% ethanol. The RNA was spun down and placed in RNAse free water. RNA was stored at −80° C.


[1044] AI_comprehensive panel_v1.0


[1045] The plates for AI_comprehensive panel_v1.0 include two control wells and 89 test samples comprised of cDNA isolated from surgical and postmortem human tissues obtained from the Backus Hospital and Clinomics (Frederick, Md.). Total RNA was extracted from tissue samples from the Backus Hospital in the Facility at CuraGen. Total RNA from other tissues was obtained from Clinomics.


[1046] Joint tissues including synovial fluid, synovium, bone and cartilage were obtained from patients undergoing total knee or hip replacement surgery at the Backus Hospital. Tissue samples were immediately snap frozen in liquid nitrogen to ensure that isolated RNA was of optimal quality and not degraded. Additional samples of osteoarthritis and rheumatoid arthritis joint tissues were obtained from Clinomics. Normal control tissues were supplied by Clinomics and were obtained during autopsy of trauma victims surgical specimens of psoriatic tissues and adjacent matched tissues were provided as total RNA by Clinomics. Two male and two female patients were selected between the ages of 25 and 47. None of the patients were taking prescription drugs at the time samples were isolated.


[1047] Surgical specimens of diseased colon from patients with ulcerative colitis and Crohns disease and adjacent matched tissues were obtained from Clinomics. Bowel tissue from three female and three male Crohn's patients between the ages of 41-69 were used. Two patients were not on prescription medication while the others were taking dexamethasone, phenobarbital, or tylenol. Ulcerative colitis tissue was from three male and four female patients. Four of the patients were taking lebvid and two were on phenobarbital.


[1048] Total RNA from post mortem lung tissue from trauma victims with no disease or with emphysema, asthma or COPD was purchased from Clinomics. Emphysema patients ranged in age from 40-70 and all were smokers, this age range was chosen to focus on patients with cigarette-linked emphysema and to avoid those patients with alpha-i anti-trypsin deficiencies. Asthma patients ranged in age from 36-75, and excluded smokers to prevent those patients that could also have COPD. COPD patients ranged in age from 35-80 and included both smokers and non-smokers. Most patients were taking corticosteroids, and bronchodilators.


[1049] In the labels employed to identify tissues in the AI_comprehensive panel_v1.0 panel, the following abbreviations are used:


[1050] AI=Autoimmunity


[1051] Syn=Synovial


[1052] Normal=No apparent disease


[1053] Rep22/Rep20=individual patients


[1054] RA=Rheumatoid arthritis


[1055] Backus=From Backus Hospital


[1056] IDA=Osteoarthritis


[1057] (SS) (BA) (MF)=Individual patients


[1058] Adj=Adjacent tissue


[1059] Match control=adjacent tissues


[1060] -M=Male


[1061] -F=Female


[1062] COPD=Chronic obstructive pulmonary disease


[1063] Panels: 5D and 5I


[1064] The plates for Panel 5D and 5I include two control wells and a variety of cDNAs isolated from human tissues and cell lines with an emphasis on metabolic diseases. Metabolic tissues were obtained from patients enrolled in the Gestational Diabetes study. Cells were obtained during different stages in the differentiation of adipocytes from human mesenchymal stem cells. Human pancreatic islets were also obtained.


[1065] In the Gestational Diabetes study subjects are young (18-40 years), otherwise healthy women with and without gestational diabetes undergoing routine (elective) Caesarean section. After delivery of the infant, when the surgical incisions were being repaired/closed, the obstetrician removed a small sample (<1 cc) of the exposed metabolic tissues during the closure of each surgical level. The biopsy material was rinsed in sterile saline, blotted and fast frozen within 5 minutes from the time of removal. The tissue was then flash frozen in liquid nitrogen and stored, individually, in sterile screw-top tubes and kept on dry ice for shipment to or to be picked up by CuraGen. The metabolic tissues of interest include uterine wall (smooth muscle), visceral adipose, skeletal muscle (rectus) and subcutaneous adipose. Patient descriptions are as follows:
671Patient 2Diabetic Hispanic, overweight, not on insulinPatient 7-9Nondiabetic Caucasian and obese (BMI > 30)Patient 10Diabetic Hispanic, overweight, on insulinPatient 11Nondiabetic African American and overweightPatient 12Diabetic Hispanic on insulin


[1066] Adipocyte differentiation was induced in donor progenitor cells obtained from Osirus (a division of Clonetics/BioWhittaker) in triplicate, except for Donor 3U which had only two replicates. Scientists at Clonetics isolated, grew and differentiated human mesenchymal stem cells (HuMSCs) for CuraGen based on the published protocol found in Mark F. Pittenger, et al., Multilineage Potential of Adult Human Mesenchymal Stem Cells Science Apr. 2, 1999: 143-147. Clonetics provided Trizol lysates or frozen pellets suitable for mRNA isolation and ds cDNA production. A general description of each donor is as follows:


[1067] Donor 2 and 3 U: Mesenchymal Stem cells, Undifferentiated Adipose


[1068] Donor 2 and 3 AM: Adipose, AdiposeMidway Differentiated


[1069] Donor 2 and 3 AD: Adipose, Adipose Differentiated


[1070] Human cell lines were generally obtained from ATCC (American Type Culture Collection), NCI or the German tumor cell bank and fall into the following tissue groups: kidney proximal convoluted tubule, uterine smooth muscle cells, small intestine, liver HepG2 cancer cells, heart primary stromal cells, and adrenal cortical adenoma cells. These cells are all cultured under standard recommended conditions and RNA extracted using the standard procedures. All samples were processed at CuraGen to produce single stranded cDNA.


[1071] Panel 5I contains all samples previously described with the addition of pancreatic islets from a 58 year old female patient obtained from the Diabetes Research Institute at the University of Miami School of Medicine. Islet tissue was processed to total RNA at an outside source and delivered to CuraGen for addition to panel 5I.


[1072] In the labels employed to identify tissues in the 5D and 5I panels, the following abbreviations are used:


[1073] GO Adipose=Greater Omentum Adipose


[1074] SK=Skeletal Muscle


[1075] UT=Uterus


[1076] PL=Placenta


[1077] AD=Adipose Differentiated


[1078] AM=Adipose Midway Differentiated


[1079] U=Undifferentiated Stem Cells


[1080] Panel CNSD.01


[1081] The plates for Panel CNSD.01 include two control wells and 94 test samples comprised of cDNA isolated from postmortem human brain tissue obtained from the Harvard Brain Tissue Resource Center. Brains are removed from calvaria of donors between 4 and 24 hours after death, sectioned by neuroanatomists, and frozen at −80° C. in liquid nitrogen vapor. All brains are sectioned and examined by neuropathologists to confirm diagnoses with clear associated neuropathology.


[1082] Disease diagnoses are taken from patient records. The panel contains two brains from each of the following diagnoses: Alzheimer's disease, Parkinson's disease, Huntington's disease, Progressive Supernuclear Palsy, Depression, and “Normal controls”. Within each of these brains, the following regions are represented: cingulate gyrus, temporal pole, globus palladus, substantia nigra, Brodman Area 4 (primary motor strip), Brodman Area 7 (parietal cortex), Brodman Area 9 (prefrontal cortex), and Brodman area 17 (occipital cortex). Not all brain regions are represented in all cases; e.g., Huntington's disease is characterized in part by neurodegeneration in the globus palladus, thus this region is impossible to obtain from confirmed Huntington's cases. Likewise Parkinson's disease is characterized by degeneration of the substantia nigra making this region more difficult to obtain. Normal control brains were examined for neuropathology and found to be free of any pathology consistent with neurodegeneration.


[1083] In the labels employed to identify tissues in the CNS panel, the following abbreviations are used:


[1084] PSP=Progressive supranuclear palsy


[1085] Sub Nigra=Substantia nigra


[1086] Glob Palladus=Globus palladus


[1087] Temp Pole=Temporal pole


[1088] Cing Gyr=Cingulate gyrus


[1089] BA4=Brodman Area 4


[1090] Panel CNS_Neurodegeneration_V1.0


[1091] The plates for Panel CNS_Neurodegeneration_V1.0 include two control wells and 47 test samples comprised of cDNA isolated from postmortem human brain tissue obtained from the Harvard Brain Tissue Resource Center (McLean Hospital) and the Human Brain and Spinal Fluid Resource Center (VA Greater Los Angeles Healthcare System). Brains are removed from calvaria of donors between 4 and 24 hours after death, sectioned by neuroanatomists, and frozen at −80° C. in liquid nitrogen vapor. All brains are sectioned and examined by neuropathologists to confirm diagnoses with clear associated neuropathology.


[1092] Disease diagnoses are taken from patient records. The panel contains six brains from Alzheimer's disease (AD) patients, and eight brains from “Normal controls” who showed no evidence of dementia prior to death. The eight normal control brains are divided into two categories: Controls with no dementia and no Alzheimer's like pathology (Controls) and controls with no dementia but evidence of severe Alzheimer's like pathology, (specifically senile plaque load rated as level 3 on a scale of 0-3; 0=no evidence of plaques, 3=severe AD senile plaque load). Within each of these brains, the following regions are represented: hippocampus, temporal cortex (Brodman Area 21), parietal cortex (Brodman area 7), and occipital cortex (Brodman area 17). These regions were chosen to encompass all levels of neurodegeneration in AD. The hippocampus is a region of early and severe neuronal loss in AD; the temporal cortex is known to show neurodegeneration in AD after the hippocampus; the parietal cortex shows moderate neuronal death in the late stages of the disease; the occipital cortex is spared in AD and therefore acts as a “control” region within AD patients. Not all brain regions are represented in all cases.


[1093] In the labels employed to identify tissues in the CNS_Neurodeeneration_V1.0 panel, the following abbreviations are used:


[1094] AD=Alzheimer's disease brain; patient was demented and showed AD-like pathology upon autopsy


[1095] Control=Control brains; patient not demented, showing no neuropathology


[1096] Control (Path)=Control brains; pateint not demented but showing sever AD-like pathology


[1097] SupTemporal Ctx=Superior Temporal Cortex


[1098] Inf Temporal Ctx=Inferior Temporal Cortex


[1099] A. CG58522-01: Human Platelet-Activating Factor Acetylhydrolase Ib Beta


[1100] Expression of gene CG58522-01 was assessed using the primer-probe set Ag3365, described in Table AA. Results of the RTQ-PCR runs are shown in Table AB.


[1101] Table AA. Probe Name Ag3365
672TABLE AAProbe Name Ag3365StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-cagaatgaaccaaggagactca-3′223357ProbeTET-5′-ctactccgcatgcggcagaagacatt-3′-TAMRA2635358Reverse5′-cacatccatctgtcatctcctt-3′2262359


[1102]

673





TABLE AB










General_screening_panel_v1.4











Rel. Exp.

Rel. Exp.



(%) Ag3365,

(%) Ag3365,



Run

Run


Tissue Name
216709759
Tissue Name
216709759













Adipose
0.0
Renal ca. TK-10
0.0


Melanoma*
0.0
Bladder
0.0


Hs688(A).T


Melanoma*
0.0
Gastric ca. (liver met.)
0.0


Hs688(B).T

NCI-N87


Melanoma* M14
0.0
Gastric ca. KATO III
0.0


Melanoma*
0.0
Colon ca. SW-948
0.0


LOXIMVI


Melanoma* SK-
0.0
Colon ca. SW480
0.0


MEL-5


Squamous cell
0.0
Colon ca.* (SW480
0.0


carcinoma SCC-4

met) SW620


Testis Pool
10.7
Colon ca. HT29
0.0


Prostate ca.* (bone
0.0
Colon ca. HCT-116
0.0


met) PC-3


Prostate Pool
0.0
Colon ca. CaCo-2
0.0


Placenta
0.0
Colon cancer tissue
0.0


Uterus Pool
0.0
Colon ca. SW1116
0.0


Ovarian ca.
0.0
Colon ca. Colo-205
0.0


OVCAR-3


Ovarian ca. SK-
4.9
Colon ca. SW-48
0.0


OV-3


Ovarian ca.
0.0
Colon Pool
0.0


OVCAR-4


Ovarian ca.
0.0
Small Intestine Pool
0.0


OVCAR-5


Ovarian ca.
7.9
Stomach Pool
0.0


IGROV-1


Ovarian ca.
26.8
Bone Marrow Pool
0.0


OVCAR-8


Ovary
0.0
Fetal Heart
0.0


Breast ca. MCF-7
0.0
Heart Pool
0.0


Breast ca. MDA-
1.7
Lymph Node Pool
16.5


MB-231


Breast ca. BT 549
0.0
Fetal Skeletal Muscle
0.0


Breast ca. T47D
0.0
Skeletal Muscle Pool
0.0


Breast ca. MDA-N
0.0
Spleen Pool
0.0


Breast Pool
0.0
Thymus Pool
0.0


Trachea
0.0
CNS cancer
0.0




(glio/astro) U87-MG


Lung
0.0
CNS cancer
0.0




(glio/astro) U-118-MG


Fetal Lung
0.0
CNS cancer
0.0




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.0
CNS cancer (astro)
0.0




SF-539


Lung ca. LX-1
3.3
CNS cancer (astro)
0.0




SNB-75


Lung ca. NCI-H146
4.5
CNS cancer (glio)
6.2




SNB-19


Lung ca. SHP-77
0.0
CNS cancer (glio) SF-
25.7




295


Lung ca. A549
0.0
Brain (Amygdala)
0.0




Pool


Lung ca. NCI-H526
0.0
Brain (cerebellum)
0.0


Lung ca. NCI-H23
100.0
Brain (fetal)
0.0


Lung ca. NCI-H460
0.0
Brain (Hippocampus)
4.8




Pool


Lung ca. HOP-62
0.0
Cerebral Cortex Pool
0.0


Lung ca. NCI-H522
0.0
Brain (Substantia
1.8




nigra) Pool


Liver
0.0
Brain (Thalamus) Pool
3.6


Fetal Liver
0.0
Brain (whole)
6.9


Liver ca. HepG2
0.0
Spinal Cord Pool
0.0


Kidney Pool
0.0
Adrenal Gland
0.0


Fetal Kidney
0.0
Pituitary gland Pool
0.0


Renal ca. 786-0
0.0
Salivary Gland
0.0


Renal ca. A498
0.0
Thyroid (female)
0.0


Renal ca. ACHN
0.0
Pancreatic ca.
0.0




CAPAN2


Renal ca. UO-31
0.0
Pancreas Pool
0.0










[1103] CNS_neurodegeneration_v1.0 Summary: Ag3365—Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1104] General_screening_panel_v1.4 Summary: Ag3365—Significant expression of this gene is seen only in the lung cancer cell line NCI-H23 (CT=33.1). Therefore, expression of this gene may be used to distinguish this sample from the other samples on this panel.


[1105] Panel 4D Summary: Ag3365—Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1106] B. CG58520-01: Gamma-Aminobutyric-Acid Receptor Gamma-1


[1107] Expression of gene CG58520-01 was assessed using the primer-probe set Ag3364, described in Table BA.


[1108] Table BA. Probe Name Ag3364
674TABLE BAProbe Name Ag3364StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-ttcttctgcggagtcaaagtag-3′2243360ProbeTET-5′-ttggtcttcttgttactgaccctgca-3′-TAMRA2675361Reverse5′-tcatctgccttatcaacgtttc-3′22106362


[1109] CNS_neurodegeneration_v1.0 Summary: Ag3364—Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1110] General_screening_panel_v1.4 Summary: Ag3364—Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1111] Panel 4D Summary: Ag3364—Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1112] Panel CNS1 Summary: Ag3364—Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1113] C. CG58520-03: Gamma-Aminobutyric-Acid Receptor Gamma-1 Subunit Precursor (Gaba(A) Receptor)


[1114] Expression of gene CG58520-03 was assessed using the primer-probe set Ag5092, described in Table CA.


[1115] Table CA. Probe Name Ag5092
675TABLE CAProbe Name Ag5092StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-gaacattcctgtccactgga-3′20625363ProbeTET-5′-attttcaagcgatggataccctaaaa-3′-TAMRA26645364Reverse5′-cacttctacggagggctttt-3′20692365


[1116] CNS_neurodegeneration_v1.0 Summary: Ag5092—Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1117] General_screening_panel_v1.5 Summary: Ag5092—Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1118] Panel 4.1D Summary: Ag5092—Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1119] D. CG58518-01: Gamma-Aminobutyric-Acid Receptor RHO-3


[1120] Expression of gene CG58518-01 was assessed using the primer-probe sets Ag3363, Ag1130, Ag1198, Ag1253 and Ag1603, described in Tables DA, DB, DC, DD and DE. Results of the RTQ-PCR runs are shown in Tables DF, DG and DH.


[1121] Table DA. Probe Name Ag3363
676TABLE DAProbe Name Ag3363StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-tggctttccagttagtctcctt-3′2214366ProbeTET-5′-cacctacatctggatcatattgaaacca-3′-TAMRA2836367Reverse5′-ttgatgttagaagcagcacaaa-3′2268368


[1122] Table DB. Probe Name Ag1130
677TABLE DBProbe Name Ag1130StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-gtcctggctttccagttagtct-3′2210369ProbeTET-5′-tcacctacatctggatcatattgaaacca-3′-TAMRA2935370Reverse5′-ttgatgttagaagcagcacaaa-3′2268371


[1123] Table DC. Probe Name Ag1198
678TABLE DCProbe Name Ag1198StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-gtcctggctttccagttagtct-3′2210372ProbeTET-5′-tcacctacatctggatcatattgaaacca-3′-TAMRA2935373Reverse5′-ttgatgttagaagcagcacaaa-3′2268374


[1124] Table DD. Probe Name Ag1253
679TABLE DDProbe Name Ag1253StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-atctgggtgcctgatatctttt-3′22466375ProbeTET-5′-tgtccactctaaaagatccttcatccatga-3′-TAMRA30489376Reverse5′-cgcagcatgatattctccatag-3′22524377


[1125] Table DE. Probe Name Ag1603
680TABLE DEProbe Name Ag1603StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-gtcctggctttccagttagtct-3′2210378ProbeTET-5′-tcacctacatctggatcatattgaaacca-3′-TAMRA2935379Reverse5′-ttgatgttagaagcagcacaaa-3′2268380


[1126]

681





TABLE DF










General_screening_panel_v1.4











Rel. Exp.

Rel. Exp.



(%) Ag3363,

(%) Ag3363,



Run

Run


Tissue Name
216709559
Tissue Name
216709559













Adipose
0.0
Renal ca. TK-10
0.0


Melanoma*
0.0
Bladder
6.6


Hs688(A).T


Melanoma*
0.0
Gastric ca. (liver met.)
0.0


Hs688(B).T

NCI-N87


Melanoma* M14
0.0
Gastric ca. KATO III
0.0


Melanoma*
0.0
Colon ca. SW-948
0.0


LOXIMVI


Melanoma* SK-
0.0
Colon ca. SW480
0.0


MEL-5


Squamous cell
0.0
Colon ca.* (SW480
0.0


carcinoma SCC-4

met) SW620


Testis Pool
16.7
Colon ca. HT29
0.0


Prostate ca.* (bone
0.0
Colon ca. HCT-116
0.0


met) PC-3


Prostate Pool
0.0
Colon ca. CaCo-2
0.0


Placenta
0.0
Colon cancer tissue
0.0


Uterus Pool
0.0
Colon ca. SW1116
0.0


Ovarian ca.
0.0
Colon ca. Colo-205
0.0


OVCAR-3


Ovarian ca. SK-
0.0
Colon ca. SW-48
0.0


OV-3


Ovarian ca.
0.0
Colon Pool
0.0


OVCAR-4


Ovarian ca.
0.0
Small Intestine Pool
0.0


OVCAR-5


Ovarian ca.
0.0
Stomach Pool
0.0


IGROV-1


Ovarian ca.
0.0
Bone Marrow Pool
0.0


OVCAR-8


Ovary
0.0
Fetal Heart
0.0


Breast ca. MCF-7
0.0
Heart Pool
0.0


Breast ca. MDA-
0.0
Lymph Node Pool
6.8


MB-231


Breast ca. BT 549
0.0
Fetal Skeletal Muscle
0.0


Breast ca. T47D
6.4
Skeletal Muscle Pool
0.0


Breast ca. MDA-N
0.0
Spleen Pool
8.5


Breast Pool
0.0
Thymus Pool
0.0


Trachea
0.0
CNS cancer
0.0




(glio/astro) U87-MG


Lung
0.0
CNS cancer
10.9




(glio/astro) U-118-MG


Fetal Lung
0.0
CNS cancer
0.0




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.0
CNS cancer (astro)
0.0




SF-539


Lung ca. LX-1
0.0
CNS cancer (astro)
0.0




SNB-75


Lung ca. NCI-H146
77.9
CNS cancer (glio)
0.0




SNB-19


Lung ca. SHP-77
100.0
CNS cancer (glio) SF-
11.4




295


Lung ca. A549
10.1
Brain (Amygdala)
0.0




Pool


Lung ca. NCI-H526
0.0
Brain (cerebellum)
0.0


Lung ca. NCI-H23
34.4
Brain (fetal)
0.0


Lung ca. NCI-H460
30.6
Brain (Hippocampus)
0.0




Pool


Lung ca. HOP-62
0.0
Cerebral Cortex Pool
0.0


Lung ca. NCI-H522
0.0
Brain (Substantia
0.0




nigra) Pool


Liver
0.0
Brain (Thalamus) Pool
5.1


Fetal Liver
0.0
Brain (whole)
50.0


Liver ca. HepG2
0.0
Spinal Cord Pool
0.0


Kidney Pool
3.0
Adrenal Gland
0.0


Fetal Kidney
8.4
Pituitary gland Pool
0.0


Renal ca. 786-0
0.0
Salivary Gland
0.0


Renal ca. A498
0.0
Thyroid (female)
0.0


Renal ca. ACHN
0.0
Pancreatic ca.
0.0




CAPAN2


Renal ca. UO-31
0.0
Pancreas Pool
0.0










[1127]

682





TABLE DG










Panel 1.2















Rel.
Rel.
Rel.

Rel.
Rel.
Rel.



Exp. (%)
Exp. (%)
Exp. (%)

Exp. (%)
Exp. (%)
Exp. (%)



Ag1130,
Ag1130,
Ag1198,

Ag1130,
Ag1130,
Ag1198,


Tissue
Run
Run
Run
Tissue
Run
Run
Run


Name
125117140
126566764
129140506
Name
125117140
126566764
129140506

















Endothelial
0.0
0.0
0.0
Renal ca.
0.0
0.0
0.0


cells



786-0


Heart
0.0
0.0
0.0
Renal ca.
7.3
4.7
0.0


(Fetal)



A498


Pancreas
0.0
0.0
0.0
Renal ca.
0.0
0.0
0.0






RXF 393


Pancreatic
9.0
0.0
0.0
Renal ca.
0.0
0.0
0.0


ca. CAPAN 2



ACHN


Adrenal
0.0
2.6
0.0
Renal ca.
3.9
0.0
0.0


Gland



UO-31


Thyroid
0.0
0.0
0.0
Renal ca.
0.0
0.0
0.0






TK-10


Salivary
0.0
0.0
0.0
Liver
26.6
0.0
0.0


gland


Pituitary
0.0
0.0
0.0
Liver
25.3
0.0
0.0


gland



(fetal)


Brain
0.0
0.0
0.0
Liver ca.
0.0
0.0
0.0


(fetal)



(hepatoblast)






HepG2


Brain
2.6
20.0
0.0
Lung
0.0
0.0
0.0


(whole)


Brain
1.3
32.1
0.0
Lung
0.0
0.0
0.0


(amygdala)



(fetal)


Brain
1.5
3.8
0.0
Lung ca.
3.4
0.0
0.0


(cerebellum)



(small






cell) LX-1


Brain
0.0
27.0
0.0
Lung ca.
28.5
74.2
0.0


(hippocampus)



(small






cell) NCI-






H69


Brain
9.9
22.5
9.8
Lung ca.
3.8
9.7
0.0


(thalamus)



(s.cell






var.)






SHP-77


Cerebral
0.0
0.0
0.0
Lung ca.
8.8
4.1
5.3


Cortex



(large






cell)NCI-






H460


Spinal cord
4.4
0.0
0.0
Lung ca.
51.4
9.5
7.2






(non-sm.






cell) A549


glio/astro
0.0
0.0
0.0
Lung ca.
0.0
0.0
0.0


U87-MG



(non-






s.cell)






NCI-H23


glio/astro
0.0
0.0
0.0
Lung ca.
8.4
2.7
9.6


U-118-MG



(non-






s.cell)






HOP-62


astrocytoma
2.9
0.0
0.0
Lung ca.
0.0
0.0
0.0


SW1783



(non-s.cl)






NCI-






H522


neuro*; met
0.0
0.0
0.0
Lung ca.
3.2
8.7
0.0


SK-N-AS



(squam.)






SW 900


astrocytoma
5.1
0.0
0.0
Lung ca.
2.3
15.9
0.0


SF-539



(squam.)






NCI-






H596


astrocytoma
2.3
0.0
0.0
Mammary
0.0
0.0
0.0


SNB-75



gland


glioma
6.3
20.7
9.0
Breast
0.0
0.0
0.0


SNB-19



ca.*






(pl.ef)






MCF-7


glioma
1.4
0.0
1.8
Breast
0.0
0.0
0.0


U251



ca.*






(pl.ef)






MDA-






MB-231


glioma SF-
0.0
0.0
0.0
Breast
14.1
37.4
0.0


295



ca.* (pl.






ef) T47D


Heart
0.0
0.0
0.0
Breast ca.
12.5
21.0
12.3






BT-549


Skeletal
2.3
0.0
0.0
Breast ca.
0.0
0.0
0.0


Muscle



MDA-N


Bone
0.0
0.0
0.0
Ovary
0.0
0.0
0.0


marrow


Thymus
0.0
0.0
0.0
Ovarian
0.0
0.0
0.0






ca.






OVCAR-3


Spleen
2.2
0.0
0.0
Ovarian
0.0
0.0
0.0






ca.






OVCAR-4


Lymph
0.0
0.0
0.0
Ovarian
66.9
35.4
4.4


node



ca.






OVCAR-5


Colorectal
11.3
27.7
21.8
Ovarian
2.7
0.0
0.0


Tissue



ca.






OVCAR-8


Stomach
0.0
0.0
0.0
Ovarian
6.0
0.0
0.0






ca.






IGROV-1


Small
5.4
0.0
0.0
Ovarian
30.8
0.0
0.0


intestine



ca.






(ascites)






SK-OV-3


Colon ca.
3.2
0.0
0.0
Uterus
0.0
0.0
0.0


SW480


Colon ca.*
0.0
0.0
0.0
Placenta
0.0
0.0
0.0


SW620


(SW480


met)


Colon ca.
1.9
14.4
0.0
Prostate
6.9
0.0
0.0


HT29


Colon ca.
0.0
0.0
0.0
Prostate
100.0
0.0
0.0


HCT-116



ca.* (bone






met) PC-3


Colon ca.
0.0
0.0
0.0
Testis
54.7
100.0
36.9


CaCo-2


Colon ca.
72.2
75.8
100.0
Melanoma
4.2
0.0
0.0


Tissue



Hs688(A).T


(ODO3866)


Colon ca.
5.3
4.8
0.0
Melanoma*
2.7
34.2
13.3


HCC-2998



(met)






Hs688(B).T


Gastric ca.*
50.3
0.0
0.0
Melanoma
0.0
0.0
0.0


(liver met)



UACC-


NCI-N87



62


Bladder
6.0
22.1
0.0
Melanoma
31.4
36.3
20.2






M14


Trachea
0.0
0.0
0.0
Melanoma
0.0
0.0
0.0






LOX






IMVI


Kidney
2.0
0.0
0.0
Melanoma*
2.4
0.0
0.0






(met)






SK-MEL-5


Kidney
1.1
2.5
0.0


(fetal)










[1128]

683





TABLE DH










Panel 4R











Rel. Exp. (%)

Rel. Exp. (%)



Ag1198, Run

Ag1198, Run


Tissue Name
142014937
Tissue Name
142014937













Secondary Th1 act
0.0
HUVEC IL-1beta
0.0


Secondary Th2 act
0.0
HUVEC IFN gamma
0.0


Secondary Tr1 act
2.5
HUVEC TNF alpha +
0.0




IFN gamma


Secondary Th1 rest
0.0
HUVEC TNF alpha +
0.0




IL4


Secondary Th2 rest
0.0
HUVEC IL-11
0.0


Secondary Tr1 rest
0.0
Lung Microvascular EC
0.0




none


Primary Th1 act
0.0
Lung Microvascular EC
0.0




TNF alpha + IL-1beta


Primary Th2 act
0.0
Microvascular Dermal
0.0




EC none


Primary Tr1 act
0.0
Microsvasular Dermal
0.0




EC TNF alpha + IL-1beta


Primary Th1 rest
0.0
Bronchial epithelium
0.0




TNF alpha + IL1beta


Primary Th2 rest
0.0
Small airway epithelium
0.0




none


Primary Tr1 rest
0.0
Small airway epithelium
0.0




TNF alpha + IL-1beta


CD45RA CD4
0.0
Coronery artery SMC rest
0.0


lymphocyte act


CD45RO CD4
0.0
Coronery artery SMC
0.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
0.0
Astrocytes rest
0.0


Secondary CD8
0.0
Astrocytes TNF alpha +
0.0


lymphocyte rest

IL-1beta


Secondary CD8
0.0
KU-812 (Basophil) rest
0.0


lymphocyte act


CD4 lymphocyte none
0.0
KU-812 (Basophil)
0.0




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
0.0
CCD1106
0.0


CD95 CH11

(Keratinocytes) none


LAK cells rest
0.0
CCD1106
0.0




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
0.0
Liver cirrhosis
16.4


LAK cells IL-2 + IL-12
0.0
Lupus kidney
0.0


LAK cells IL-2 + IFN
0.0
NCI-H292 none
0.0


gamma


LAK cells IL-2 + IL-18
0.0
NCI-H292 IL-4
0.0


LAK cells
0.0
NCI-H292 IL-9
0.0


PMA/ionomycin


NK Cells IL-2 rest
0.0
NCI-H292 IL-13
0.0


Two Way MLR 3 day
0.0
NCI-H292 IFN gamma
0.0


Two Way MLR 5 day
0.0
HPAEC none
0.0


Two Way MLR 7 day
0.0
HPAEC TNF alpha + IL-
0.0




1beta


PBMC rest
0.0
Lung fibroblast none
0.0


PBMC PWM
0.0
Lung fibroblast TNF
0.0




alpha + IL-1beta


PBMC PHA-L
0.0
Lung fibroblast IL-4
0.0


Ramos (B cell) none
0.0
Lung fibroblast IL-9
0.0


Ramos (B cell)
0.0
Lung fibroblast IL-13
0.0


ionomycin


B lymphocytes PWM
0.0
Lung fibroblast IFN
0.0




gamma


B lymphocytes CD40L
0.0
Dermal fibroblast
0.0


and IL-4

CCD1070 rest


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0




CCD1070 TNF alpha


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
0.0
Dermal fibroblast IFN
0.0




gamma


Dendritic cells LPS
0.0
Dermal fibroblast IL-4
0.0


Dendritic cells anti-
0.0
IBD Colitis 1
100.0


CD40


Monocytes rest
0.0
IBD Colitis 2
0.0


Monocytes LPS
0.0
IBD Crohn's
0.0


Macrophages rest
0.0
Colon
0.0


Macrophages LPS
0.0
Lung
0.0


HUVEC none
0.0
Thymus
0.0


HUVEC starved
0.0
Kidney
0.0










[1129] CNS_neurodegeneration_v1.0 Summary: Ag3363—Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1130] General_screening_panel_v1.4 Summary: Ag3363—Significant expression is seen in lung cancer cell line NCI-H1146 (CT=34.5) and lung cancer cell line SHP-77 (CT=34.2). Therefore, expression of this can be used to distinguish these samples from the rest of the samples on this panel.


[1131] Panel 1.2 Summary: Ag1130/Ag1198—Three different runs using the same primer sequences yield similar results. Significant expression of this gene is seen in testis and a colon cancer sample. Therefore, expression of this gene can be used to differentiate these samples from other samples on these panels. Results from a third experiment using the probe and primer set Ag1253 show low/undetectable levels of expression in all the samples on this panel.


[1132] Panel 1.3D Summary: Ag1253—Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1133] Panel 2D Summary: Ag1603—Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown)


[1134] Panel 4D Summary: Ag1130/Ag1198/Ag1253/Ag3363—Two experiments showed possible experimental difficulties, while the other three runs showed expression of this gene as low/undetectable (CTs>35) across all of the samples on the panel.


[1135] Panel 4R Summary: Ag1198—Significant expression of this gene is seen only in the IBD colitis 1 sample (CT=34.2). Therefore, expression of this gene can be used to differentiate this sample from others on the panel.


[1136] Panel CNS 1 Summary: Ag1253/Ag1603—Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1137] E. CG58516-01: G-Protein Beta WD-40 Repeats


[1138] Expression of gene CG58516-01 was assessed using the primer-probe set Ag3362, described in Table EA. Results of the RTQ-PCR runs are shown in Tables EB and EC.


[1139] Table EA. Probe Name Ag3362
684TABLE EAProbe Name Ag3362StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-gtcgggcaggacctttact-3′191474381ProbeTET-5′-tcctacagctaattctgcagggcaca-3′-TAMRA261498382Reverse5′-tacgctttactcccgtaagtca-3′221543383


[1140]

685





TABLE EB










CNS_neurodegeneration_v1.0













Rel. Exp.



Rel. Exp. (%)

(%) Ag3362,



Ag3362, Run

Run


Tissue Name
210153738
Tissue Name
210153738













AD 1 Hippo
9.9
Control (Path) 3
0.0




Temporal Ctx


AD 2 Hippo
33.2
Control (Path) 4
24.3




Temporal Ctx


AD 3 Hippo
4.3
AD 1 Occipital
2.0




Ctx


AD 4 Hippo
16.5
AD 2 Occipital
0.0




Ctx (Missing)


AD 5 hippo
96.6
AD 3 Occipital
5.4




Ctx


AD 6 Hippo
43.2
AD 4 Occipital
24.7




Ctx


Control 2 Hippo
29.1
AD 5 Occipital
24.5




Ctx


Control 4 Hippo
16.6
AD 6 Occipital
31.9




Ctx


Control (Path) 3
3.8
Control 1 Occipital
0.9


Hippo

Ctx


AD 1 Temporal Ctx
7.1
Control 2 Occipital
89.5




Ctx


AD 2 Temporal Ctx
23.2
Control 3 Occipital
12.6




Ctx


AD 3 Temporal Ctx
5.6
Control 4 Occipital
6.3




Ctx


AD 4 Temporal Ctx
20.0
Control (Path) 1
65.1




Occipital Ctx


AD 5 Inf Temporal
100.0
Control (Path) 2
15.8


Ctx

Occipital Ctx


AD 5 SupTemporal
43.8
Control (Path) 3
2.0


Ctx

Occipital Ctx


AD 6 Inf Temporal
30.8
Control (Path) 4
11.6


Ctx

Occipital Ctx


AD 6 Sup Temporal
69.7
Control 1 Parietal
2.8


Ctx

Ctx


Control 1 Temporal
9.0
Control 2 Parietal
39.2


Ctx

Ctx


Control 2 Temporal
59.0
Control 3 Parietal
23.5


Ctx

Ctx


Control 3 Temporal
11.7
Control (Path) 1
69.7


Ctx

Parietal Ctx


Control 4 Temporal
8.2
Control (Path) 2
14.9


Ctx

Parietal Ctx


Control (Path) 1
56.3
Control (Path) 3
0.9


Temporal Ctx

Parietal Ctx


Control (Path) 2
34.2
Control (Path) 4
38.7


Temporal Ctx

Parietal Ctx










[1141]

686





TABLE EC










General_screening_panel_v1.4











Rel. Exp.

Rel. Exp.



(%) Ag3362,

(%) Ag3362,



Run

Run


Tissue Name
216523482
Tissue Name
216523482













Adipose
6.3
Renal ca. TK-10
44.1


Melanoma*
17.6
Bladder
9.4


Hs688(A).T


Melanoma*
18.3
Gastric ca. (liver met.)
21.6


Hs688(B).T

NCI-N87


Melanoma* M14
17.1
Gastric ca. KATO III
17.6


Melanoma*
13.6
Colon ca. SW-948
5.8


LOXIMVI


Melanoma* SK-
19.6
Colon ca. SW480
34.6


MEL-5


Squamous cell
14.6
Colon ca.* (SW480
14.2


carcinoma SCC-4

met) SW620


Testis Pool
4.0
Colon ca. HT29
7.2


Prostate ca.* (bone
90.8
Colon ca. HCT-116
14.3


met) PC-3


Prostate Pool
4.0
Colon ca. CaCo-2
19.8


Placenta
11.4
Colon cancer tissue
3.6


Uterus Pool
2.1
Colon ca. SW1116
9.4


Ovarian ca.
17.4
Colon ca. Colo-205
8.8


OVCAR-3


Ovarian ca. SK-
47.0
Colon ca. SW-48
13.2


OV-3


Ovarian ca.
14.7
Colon Pool
5.7


OVCAR-4


Ovarian ca.
31.6
Small Intestine Pool
10.2


OVCAR-5


Ovarian ca.
12.9
Stomach Pool
6.2


IGROV-1


Ovarian ca.
6.7
Bone Marrow Pool
1.3


OVCAR-8


Ovary
12.5
Fetal Heart
1.1


Breast ca. MCF-7
75.8
Heart Pool
3.4


Breast ca. MDA-
30.4
Lymph Node Pool
8.7


MB-231


Breast ca. BT 549
65.5
Fetal Skeletal Muscle
2.3


Breast ca. T47D
100.0
Skeletal Muscle Pool
9.4


Breast ca. MDA-N
33.4
Spleen Pool
4.6


Breast Pool
4.6
Thymus Pool
7.3


Trachea
7.7
CNS cancer
33.9




(glio/astro) U87-MG


Lung
4.9
CNS cancer
27.2




(glio/astro) U-118-MG


Fetal Lung
7.1
CNS cancer
16.0




(neuro; met) SK-N-AS


Lung ca. NCI-N417
9.3
CNS cancer (astro)
14.3




SF-539


Lung ca. LX-1
15.8
CNS cancer (astro)
60.7




SNB-75


Lung ca. NCI-H146
4.9
CNS cancer (glio)
13.8




SNB-19


Lung ca. SHP-77
16.5
CNS cancer (glio) SF-
28.5




295


Lung ca. A549
27.2
Brain (Amygdala)
5.3




Pool


Lung ca. NCI-H526
4.1
Brain (cerebellum)
5.0


Lung ca. NCI-H23
15.0
Brain (fetal)
16.4


Lung ca. NCI-H460
9.5
Brain (Hippocampus)
5.5




Pool


Lung ca. HOP-62
7.6
Cerebral Cortex Pool
8.7


Lung ca. NCI-H522
18.2
Brain (Substantia
8.3




nigra) Pool


Liver
0.0
Brain (Thalamus) Pool
6.3


Fetal Liver
7.3
Brain (whole)
7.0


Liver ca. HepG2
29.5
Spinal Cord Pool
5.6


Kidney Pool
17.7
Adrenal Gland
6.3


Fetal Kidney
4.6
Pituitary gland Pool
0.8


Renal ca. 786-0
17.2
Salivary Gland
5.6


Renal ca. A498
5.1
Thyroid (female)
9.7


Renal ca. ACHN
17.3
Pancreatic ca.
11.7




CAPAN2


Renal ca. UO-31
11.1
Pancreas Pool
9.2










[1142] CNS_neurodegeneration_v1.0 Summary: Ag3362 Highest expression of the CG58516-01 gene is seen in the occipital cortex of a control patient and the temporal cortex of an Alzheimer's patient. While the CG58516-01 gene does not appear to be preferentially expressed in Alzheimer's disease, this panel confirms expression of the CG58516-01 gene at moderate/high levels in the brain in an additional set of individuals. Please see Panel 1.4 for discussion of potential utility of this gene in the central nervous system.


[1143] General_screening_panel_v1.4 Summary: Ag3362 The CG58516-01 gene is widely expressed in this panel, with highest expression in the breast cancer cell line T47D (CT=29). Significant expression is also seen in cell lines derived from prostate, breast and ovarian cancers. In general, expression of the CG58516-0l gene appears to be greater in the cancer cell lines than in normal tissue. Thus, the expression of this gene could be used to distinguish these cell line types from others in the panel.


[1144] Among tissues involved in central nervous system function, this gene is expressed at low but significant levels in all brain regions examined. This gene encodes a protein with a putativie zinc-finger motif. Since these proteins are known to interact with nucleic acids, this suggests that this gene product may play a potential role in transcription. Thus, therapeutic modulation of the CG58516-01 gene product may be used to regulate the transcription of disease-related proteins such as ataxin, huntingtin, or various apoptosis cascade proteins.


[1145] Among tissues with metabolic function, this gene is expressed at low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, skeletal muscle, heart, and fetal liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.



REFERENCES

[1146] 1. Zhu W, Chan E K, Li J, Hemmerich P, Tan E M. (2001) Transcription activating property of autoantigen SG2NA and modulating effect of WD-40 repeats. Exp Cell Res. 269(2):312-21


[1147] Panel 4D Summary: Ag3362 Results from one experiment with the CG58516-01 gene are not included because the amp plot corresponding to the run indicates that there were problems with the experiment.


[1148] F. CG58473-01: Protein Kinase


[1149] Expression of gene CG58473-01 was assessed using the primer-probe set Ag3357, described in Table FA. Results of the RTQ-PCR runs are shown in Tables FB and FC.


[1150] Table FA. Probe Name Ag3357
687TABLE FAProbe Name Ag3357StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-gtcaaggtggccctaaaattc-3′21853384ProbeTET-5′-ccaggacctcatctccaagctgctta-3′-TAMRA26897385Reverse5′-agccgttctgaggggttat-3′19926386


[1151]

688





TABLE FB










General_screening_panel_v1.4











Rel. Exp.

Rel. Exp.



(%) Ag3357,

(%) Ag3357,



Run

Run


Tissue Name
216523477
Tissue Name
216523477













Adipose
0.0
Renal ca. TK-10
13.2


Melanoma*
0.0
Bladder
7.2


Hs688(A).T


Melanoma*
1.1
Gastric ca. (liver met.)
5.4


Hs688(B).T

NCI-N87


Melanoma* M14
50.0
Gastric ca. KATO III
49.0


Melanoma*
33.0
Colon ca. SW-948
14.9


LOXIMVI


Melanoma* SK-
24.7
Colon ca. SW480
95.9


MEL-5


Squamous cell
11.6
Colon ca.* (SW480
53.6


carcinoma SCC-4

met) SW620


Testis Pool
8.2
Colon ca. HT29
10.3


Prostate ca.* (bone
3.2
Colon ca. HCT-116
76.3


met) PC-3


Prostate Pool
0.0
Colon ca. CaCo-2
14.1


Placenta
2.4
Colon cancer tissue
6.3


Uterus Pool
0.0
Colon ca. SW1116
18.6


Ovarian ca.
51.1
Colon ca. Colo-205
24.3


OVCAR-3


Ovarian ca. SK-
53.2
Colon ca. SW-48
26.1


OV-3


Ovarian ca.
10.4
Colon Pool
4.6


OVCAR-4


Ovarian ca.
12.3
Small Intestine Pool
1.7


OVCAR-5


Ovarian ca.
10.1
Stomach Pool
1.2


IGROV-1


Ovarian ca.
13.4
Bone Marrow Pool
1.0


OVCAR-8


Ovary
0.0
Fetal Heart
0.0


Breast ca. MCF-7
20.3
Heart Pool
0.0


Breast ca. MDA-
65.1
Lymph Node Pool
1.4


MB-231


Breast ca. BT 549
100.0
Fetal Skeletal Muscle
0.0


Breast ca. T47D
34.2
Skeletal Muscle Pool
1.6


Breast ca. MDA-N
36.3
Spleen Pool
3.4


Breast Pool
1.3
Thymus pool
4.7


Trachea
0.0
CNS cancer
7.8




(glio/astro) U87-MG


Lung
0.0
CNS cancer
54.0




(glio/astro) U-118-MG


Fetal Lung
5.0
CNS cancer
7.9




(neuro; met) SK-N-AS


Lung ca. NCI-N417
17.9
CNS cancer (astro)
22.4




SF-539


Lung ca. LX-1
28.5
CNS cancer (astro)
19.2




SNB-75


Lung ca. NCI-H146
74.7
CNS cancer (glio)
14.6




SNB-19


Lung ca. SHP-77
40.6
CNS cancer (glio) SF-
3.0




295


Lung ca. A549
64.6
Brain (Amygdala)
0.0




Pool


Lung ca. NCI-H526
23.8
Brain (cerebellum)
0.0


Lung ca. NCI-H23
63.7
Brain (fetal)
0.0


Lung ca. NCI-H460
0.8
Brain (Hippocampus)
0.0




Pool


Lung ca. HOP-62
2.0
Cerebral Cortex Pool
0.0


Lung ca. NCI-H522
34.4
Brain (Substantia
2.6




nigra) Pool


Liver
0.0
Brain (Thalamus) Pool
9.3


Fetal Liver
0.0
Brain (whole)
2.5


Liver ca. HepG2
11.4
Spinal Cord Pool
0.0


Kidney Pool
0.0
Adrenal Gland
0.0


Fetal Kidney
3.1
Pituitary gland Pool
1.4


Renal ca. 786-0
20.0
Salivary Gland
0.0


Renal ca. A498
3.6
Thyroid (female)
0.0


Renal ca. ACHN
18.9
Pancreatic ca.
20.4




CAPAN2


Renal ca. UO-31
10.4
Pancreas Pool
1.3










[1152]

689





TABLE FC










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3357, Run

Ag3357, Run


Tissue Name
165231196
Tissue Name
165231196













Secondary Th1 act
9.0
HUVEC IL-1beta
9.5


Secondary Th2 act
43.2
HUVEC IFN gamma
6.3


Secondary Tr1 act
46.0
HUVEC TNF alpha +
7.3




IFN gamma


Secondary Th1 rest
6.7
HUVEC TNF alpha +
25.3




IL4


Secondary Th2 rest
12.2
HUVEC IL-11
13.1


Secondary Tr1 rest
1.9
Lung Microvascular EC
3.3




none


Primary Th1 act
6.1
Lung Microvascular EC
7.1




TNF alpha + IL-1beta


Primary Th2 act
21.8
Microvascular Dermal
10.9




EC none


Primary Tr1 act
33.0
Microsvasular Dermal
7.3




EC TNF alpha + IL-1beta


Primary Th1 rest
28.1
Bronchial epithelium
1.9




TNF alpha + IL1beta


Primary Th2 rest
12.1
Small airway epithelium
3.6




none


Primary Tr1 rest
29.7
Small airway epithelium
36.3




TNF alpha + IL-1beta


CD45RA CD4
28.5
Coronery artery SMC rest
0.0


lymphocyte act


CD45RO CD4
39.8
Coronery artery SMC
0.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
18.6
Astrocytes rest
1.4


Secondary CD8
26.8
Astrocytes TNF alpha +
1.2


lymphocyte rest

IL-1beta


Secondary CD8
19.2
KU-812 (Basophil) rest
18.2


lymphocyte act


CD4 lymphocyte none
10.6
KU-812 (Basophil)
30.4




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
15.6
CCD1106
18.3


CD95 CH11

(Keratinocytes) none


LAK cells rest
0.0
CCD1106
7.7




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
42.6
Liver cirrhosis
25.7


LAK cells IL-2 + IL-12
24.0
Lupus kidney
0.0


LAK cells IL-2 + IFN
24.8
NCI-H292 none
7.8


gamma


LAK cells IL-2 + IL-18
40.3
NCI-H292 IL-4
26.4


LAK cells
0.0
NCI-H292 IL-9
29.7


PMA/ionomycin


NK Cells IL-2 rest
23.5
NCI-H292 IL-13
20.7


Two Way MLR 3 day
13.7
NCI-H292 IFN gamma
27.9


Two Way MLR 5 day
13.2
HPAEC none
8.6


Two Way MLR 7 day
11.7
HPAEC TNF alpha + IL-
2.4




1beta


PBMC rest
0.0
Lung fibroblast none
5.5


PBMC PWM
52.1
Lung fibroblast TNF
2.2




alpha + IL-1beta


PBMC PHA-L
14.6
Lung fibroblast IL-4
0.0


Ramos (B cell) none
16.5
Lung fibroblast IL-9
0.0


Ramos (B cell)
14.7
Lung fibroblast IL-13
0.0


ionomycin


B lymphocytes PWM
100.0
Lung fibroblast IFN
0.0




gamma


B lymphocytes CD40L
10.4
Dermal fibroblast
40.1


and IL-4

CCD1070 rest


EOL-1 dbcAMP
9.9
Dermal fibroblast
43.8




CCD1070 TNF alpha


EOL-1 dbcAMP
13.2
Dermal fibroblast
23.5


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
4.7
Dermal fibroblast IFN
3.7




gamma


Dendritic cells LPS
1.1
Dermal fibroblast IL-4
4.6


Dendritic cells anti-
0.0
IBD Colitis 2
0.0


CD40


Monocytes rest
0.0
IBD Crohn's
0.0


Monocytes LPS
0.0
Colon
28.1


Macrophages rest
4.3
Lung
59.0


Macrophages LPS
0.0
Thymus
0.0


HUVEC none
28.3
Kidney
10.0


HUVEC starved
25.3










[1153] CNS_neurodegeneration_v1.0 Summary: Ag3357—Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1154] General_screening_panel_v1.4 Summary: Ag3357 This gene is primarily expressed in cancer cell lines, with highest expression in a breast cancer cell line BT 549(CT=32.8). This gene is expressed in the following cell lines but not the corresponding healthy tissue: gastric, brain, colon, lung, breast, ovarian cancer and melanomas. Thus, expression of this gene could be used as a diagnostic marker for the presence of these cancers. Furthermore, therapeutic inhibition using antibodies or small molecule drugs might be of use in the treatment of these cancers.


[1155] Panel 4D Summary: Ag3357 Highest expression of the CG58473-01 gene is seen in pokeweed mitogen-activated purified peripheral blood B lymphocytes (CT=33.2). In addition, no expression of the transcript is seen in PBMC that contain normal B cells, but the transcript is induced when PBMC are treated with the B cell selective pokeweed mitogen. The transcript is not seen in the B cell lymphoma cell line Ramos regardless of stimulation. Thus, the putative protein encoded by this gene could potentially be used diagnostically to identify activated B cells. Therefore, therapeutics that antagonize the function of this gene product may be useful as therapeutic drugs to reduce or eliminate the symptoms in patients with autoimmune and inflammatory diseases in which B cells play a part in the intiation or progression of the disease process, such as lupus erythematosus, Crohn's disease, ulcerative colitis, multiple sclerosis, chronic obstructive pulmonary disease, asthma, emphysema, rheumatoid arthritis, or psoriasis.


[1156] G. CG58470-01: UDP-N-Acetylhexosamine Pyrophosphorylase


[1157] Expression of gene CG58470-01 was assessed using the primer-probe set Ag5940, described in Table GA.


[1158] Table GA. Probe Name Ag5940
690TABLE GAProbe Name Ag5940SEQStartIDPrimersSequencesLengthPositionNO:Forward5′-atatcctgaagctacaacagttagct-3′26422387ProbeTET-5′-tggcaacaaatgcattattccatattacg-3′-TAMRA29459388Reverse5′-gagtgaactcgctggtcatg-3′20489389


[1159] General_screening_panel_v1.5 Summary: Ag5940—Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1160] Panel 5 Islet Summary: Ag5940—Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1161] H. CG58593-01: Ubiquitin-52


[1162] Expression of gene CG58593-01 was assessed using the primer-probe set Ag3421, described in Table HA.


[1163] Table HA. Probe Name Ag3421
691TABLE HAProbe Name Ag3421StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-atctgctgcaagtgctatgc-3′20291390ProbeTET-5′-cggtgctatcaactgccacaagaaga-3′-TAMRA26323391Reverse5′-tgaccttcttcctggggtac-3′20371392


[1164] CNS_neurodegeneration_v1.0 Summary: Ag3421—Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1165] General_screening_panel_v1.4 Summary: Ag3421—Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1166] Panel 4D Summary: Ag3421—Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1167] I. CG57871-01: Tousled-Like Kinase


[1168] Expression of gene CG57871-01 was assessed using the primer-probe set Ag3351, described in Table IA. Results of the RTQ-PCR runs are shown in Tables IB and IC.


[1169] Table IA. Probe Name Ag3351
692TABLE IAProbe Name Ag3351StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-gatcctcactgcaacattcttt-3′22346393ProbeTET-5′-aatcccttaccgcgacgagtagaaca-3′-TAMRA26372394Revers5′-gcactgccatctaaaccataga-3′22403395


[1170]

693





TABLE IB










CNS_neurodegeneration_v1.0











Rel. Exp.





(%) Ag3351,

Rel. Exp.(%)



Run

Ag3351, Run


Tissue Name
210141594
Tissue Name
210141594













AD 1 Hippo
10.4
Control (Path) 3
3.0




Temporal Ctx


AD 2 Hippo
33.4
Control (Path) 4
65.1




Temporal Ctx


AD 3 Hippo
5.5
AD 1 Occipital
20.2




Ctx


AD 4 Hippo
8.4
AD 2 Occipital
0.0




Ctx (Missing)


AD 5 hippo
100.0
AD 3 Occipital
3.8




Ctx


AD 6 Hippo
33.4
AD 4 Occipital
45.1




Ctx


Control 2 Hippo
29.9
AD 5 Occipital
15.2




Ctx


Control 4 Hippo
6.7
AD 6 Occipital
46.7




Ctx


Control (Path) 3
3.7
Control 1 Occipital
2.7


Hippo

Ctx


AD 1 Temporal Ctx
16.8
Control 2 Occipital
52.5




Ctx


AD 2 Temporal Ctx
45.1
Control 3 Occipital
45.4




Ctx


AD 3 Temporal Ctx
6.9
Control 4 Occipital
6.3




Ctx


AD 4 Temporal Ctx
54.0
Control (Path) 1
79.0




Occipital Ctx


AD 5 Inf Temporal
92.0
Control (Path) 2
34.4


Ctx

Occipital Ctx


AD 5 SupTemporal
13.0
Control (Path) 3
0.8


Ctx

Occipital Ctx


AD 6 Inf Temporal
48.6
Control (Path) 4
40.6


Ctx

Occipital Ctx


AD 6 Sup Temporal
56.6
Control 1 Parietal
6.9


Ctx

Ctx


Control 1 Temporal
6.2
Control 2 Parietal
48.0


Ctx

Ctx


Control 2 Temporal
29.3
Control 3 Parietal
26.1


Ctx

Ctx


Control 3 Temporal
32.8
Control (Path) 1
73.7


Ctx

Parietal Ctx


Control 4 Temporal
13.9
Control (Path) 2
57.4


Ctx

Parietal Ctx


Control (Path) 1
79.6
Control (Path) 3
3.4


Temporal Ctx

Parietal Ctx


Control (Path) 2
97.3
Control (Path) 4
78.5


Temporal Ctx

Parietal Ctx










[1171]

694





TABLE IC










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3351, Run

Ag3351, Run


Tissue Name
165222896
Tissue Name
165222896













Secondary Th1 act
16.5
HUVEC IL-1beta
15.4


Secondary Th2 act
26.4
HUVEC IFN gamma
13.5


Secondary Tr1 act
23.3
HUVEC TNF alpha +
17.0




IFN gamma


Secondary Th1 rest
6.0
HUVEC TNF alpha +
11.0




IL4


Secondary Th2 rest
10.7
HUVEC IL-11
5.4


Secondary Tr1 rest
2.1
Lung Microvascular EC
12.4




none


Primary Th1 act
19.2
Lung Microvascular EC
9.6




TNF alpha + IL-1beta


Primary Th2 act
17.6
Microvascular Dermal
14.7




EC none


Primary Tr1 act
36.1
Microsvasular Dermal
14.8




EC TNF alpha + IL-1beta


Primary Th1 rest
55.5
Bronchial epithelium
14.1




TNF alpha + IL1beta


Primary Th2 rest
43.8
Small airway epithelium
7.7




none


Primary Tr1 rest
15.9
Small airway epithelium
50.3




TNF alpha + IL-1beta


CD45RA CD4
13.0
Coronery artery SMC rest
15.6


lymphocyte act


CD45RO CD4
21.0
Coronery artery SMC
6.1


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
12.9
Astrocytes rest
11.5


Secondary CD8
14.9
Astrocytes TNF alpha +
11.8


lymphocyte rest

IL-1beta


Secondary CD8
14.8
KU-812 (Basophil) rest
19.2


lymphocyte act


CD4 lymphocyte none
10.7
KU-812 (Basophil)
54.0




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
12.7
CCD1106
12.2


CD95 CH11

(Keratinocytes) none


LAK cells rest
17.2
CCD1106
9.0




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
22.4
Liver cirrhosis
7.4


LAK cells IL-2 + IL-12
20.4
Lupus kidney
3.4


LAK cells IL-2 + IFN
37.9
NCI-H292 none
47.6


gamma


LAK cells IL-2 + IL-18
18.6
NCI-H292 IL-4
42.3


LAK cells
10.5
NCI-H292 IL-9
30.4


PMA/ionomycin


NK Cells IL-2 rest
17.8
NCI-H292 IL-13
15.7


Two Way MLR 3 day
33.2
NCI-H292 IFN gamma
25.5


Two Way MLR 5 day
10.6
HPAEC none
13.5


Two Way MLR 7 day
9.9
HPAEC TNF alpha + IL-
17.7




1beta


PBMC rest
12.8
Lung fibroblast none
11.5


PBMC PWM
63.3
Lung fibroblast TNF
12.4




alpha + IL-1beta


PBMC PHA-L
18.0
Lung fibroblast IL-4
31.2


Ramos (B cell) none
14.0
Lung fibroblast IL-9
22.2


Ramos (B cell)
77.9
Lung fibroblast IL-13
27.4


ionomycin


B lymphocytes PWM
100.0
Lung fibroblast IFN
44.8




gamma


B lymphocytes CD40L
30.8
Dermal fibroblast
33.7


and IL-4

CCD1070 rest


EOL-1 dbcAMP
11.3
Dermal fibroblast
50.0




CCD1070 TNF alpha


EOL-1 dbcAMP
13.7
Dermal fibroblast
13.4


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
14.7
Dermal fibroblast IFN
14.3




gamma


Dendritic cells LPS
19.8
Dermal fibroblast IL-4
25.7


Dendritic cells anti-
14.2
IBD Colitis 2
2.0


CD40


Monocytes rest
22.5
IBD Crohn's
3.2


Monocytes LPS
32.8
Colon
26.8


Macrophages rest
31.0
Lung
14.6


Macrophages LPS
30.8
Thymus
28.7


HUVEC none
18.3
Kidney
45.4


HUVEC starved
45.7










[1172] CNS_neurodegeneration_v1.0 Summary: Ag3351—This panel confirms the expression of this gene at low levels in the brain in an independent group of individuals. While no differential expression of this gene is detected between Alzheimer's diseased postmortem brains and those of non-demented controls, the widespread expression of this gene in the brain suggests that therapeutic modulation of the expression or function of this gene may be effective in the treatment of neurologic disorders such as Parkinson's disease, epilepsy, stroke and multiple sclerosis.


[1173] General_screening_panel_v1.4 Summary: Ag3351—Results from one experiment are not included. The amp plot indicates that there were experimental difficulties with this run.


[1174] Panel 4D Summary: Ag3351 The CG57871-01 gene is expressed at high to moderate levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.


[1175] J. CG58590-01 and CG58590-02: PALS Guanylate Kinase


[1176] Expression of gene CG58590-01 and CG58590-02 was assessed using the primer-probe set Ag3380, described in Table JA. Results of the RTQ-PCR runs are shown in Tables JB, JC and JD. Please note that CG58590-02 represents a full-length physical clone of the CG58590-01 gene, validating the prediction of the gene sequence.


[1177] Table JA. Probe Name Ag3380
695TABLE JAProbe Name Ag3380StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-tttgatacggcaattgtgaatt-3′221931396ProbeTET-5′-ccgatcttgataaagcctatcaggaa-3′-TAMRA261953397Reverse5′-cccactgaggttcagtatcaag-3′222000398


[1178]

696





TABLE JB










CNS_neurodegeneration_v1.0













Rel. Exp.



Rel. Exp. (%)

(%) Ag3380,



Ag3380, Run

Run


Tissue Name
210153753
Tissue Name
210153753













AD 1 Hippo
12.9
Control (Path) 3
4.7




Temporal Ctx


AD 2 Hippo
27.7
Control (Path) 4
24.3




Temporal Ctx


AD 3 Hippo
4.8
AD 1 Occipital
15.6




Ctx


AD 4 Hippo
7.7
AD 2 Occipital
0.0




Ctx (Missing)


AD 5 hippo
100.0
AD 3 Occipital
7.5




Ctx


AD 6 Hippo
64.2
AD 4 Occipital
19.1




Ctx


Control 2 Hippo
25.5
AD 5 Occipital
29.5




Ctx


Control 4 Hippo
9.9
AD 6 Occipital
40.1




Ctx


Control (Path) 3
8.4
Control 1 Occipital
4.2


Hippo

Ctx


AD 1 Temporal Ctx
17.6
Control 2 Occipital
65.5




Ctx


AD 2 Temporal Ctx
25.3
Control 3 Occipital
13.4




Ctx


AD 3 Temporal Ctx
4.9
Control 4 Occipital
6.4




Ctx


AD 4 Temporal Ctx
17.4
Control (Path) 1
78.5




Occipital Ctx


AD 5 Inf Temporal
81.8
Control (Path) 2
9.4


Ctx

Occipital Ctx


AD 5 SupTemporal
42.9
Control (Path) 3
3.2


Ctx

Occipital Ctx


AD 6 Inf Temporal
48.6
Control (Path) 4
9.9


Ctx

Occipital Ctx


AD 6 Sup Temporal
53.6
Control 1 Parietal
6.0


Ctx

Ctx


Control 1 Temporal
5.7
Control 2 Parietal
37.1


Ctx

Ctx


Control 2 Temporal
34.6
Control 3 Parietal
16.5


Ctx

Ctx


Control 3 Temporal
10.2
Control (Path) 1
67.4


Ctx

Parietal Ctx


Control 4 Temporal
7.1
Control (Path) 2
18.7


Ctx

Parietal Ctx


Control (Path) 1
41.5
Control (Path) 3
3.3


Temporal Ctx

Parietal Ctx


Control (Path) 2
29.5
Control (Path) 4
34.4


Temporal Ctx

Parietal Ctx










[1179]

697





TABLE JC










General_screening_panel_v1.4











Rel. Exp.

Rel. Exp.



(%) Ag3380,

(%) Ag3380,



Run

Run


Tissue Name
217043276
Tissue Name
217043276













Adipose
9.0
Renal ca. TK-10
25.5


Melanoma*
18.9
Bladder
15.9


Hs688(A).T


Melanoma*
16.8
Gastric ca. (liver met.)
52.5


Hs688(B).T

NCI-N87


Melanoma* M14
14.9
Gastric ca. KATO III
34.6


Melanoma*
21.6
Colon ca. SW-948
4.9


LOXIMVI


Melanoma* SK-
27.0
Colon ca. SW480
82.4


MEL-5


Squamous cell
28.7
Colon ca.* (SW480
20.6


carcinoma SCC-4

met) SW620


Testis Pool
5.1
Colon ca. HT29
9.2


Prostate ca.* (bone
59.9
Colon ca. HCT-116
20.6


met) PC-3


Prostate Pool
8.6
Colon ca. CaCo-2
22.8


Placenta
3.9
Colon cancer tissue
10.1


Uterus Pool
1.9
Colon ca. SW1116
6.2


Ovarian ca.
32.5
Colon ca. Colo-205
4.9


OVCAR-3


Ovarian ca. SK-
57.4
Colon ca. SW-48
4.2


OV-3


Ovarian ca.
14.7
Colon Pool
11.4


OVCAR-4


Ovarian ca.
59.5
Small Intestine Pool
9.8


OVCAR-5


Ovarian ca.
13.1
Stomach Pool
7.4


IGROV-1


Ovarian ca.
19.2
Bone Marrow Pool
4.2


OVCAR-8


Ovary
5.9
Fetal Heart
6.3


Breast ca. MCF-7
35.1
Heart Pool
4.9


Breast ca. MDA-
58.2
Lymph Node Pool
11.4


MB-231


Breast ca. BT 549
26.8
Fetal Skeletal Muscle
3.3


Breast ca. T47D
100.0
Skeletal Muscle Pool
8.1


Breast ca. MDA-N
8.7
Spleen Pool
5.6


Breast Pool
10.4
Thymus Pool
6.3


Trachea
5.5
CNS cancer
39.2




(glio/astro) U87-MG


Lung
3.8
CNS cancer
54.7




(glio/astro) U-118-MG


Fetal Lung
11.8
CNS cancer
19.6




(neuro; met) SK-N-AS


Lung ca. NCI-N417
3.2
CNS cancer (astro)
12.2




SF-539


Lung ca. LX-1
20.7
CNS cancer (astro)
29.7




SNB-75


Lung ca. NCI-H146
3.8
CNS cancer (glio)
13.4




SNB-19


Lung ca. SHP-77
17.9
CNS cancer (glio) SF-
28.9




295


Lung ca. A549
30.6
Brain (Amygdala)
11.8




Pool


Lung ca. NCI-H526
3.6
Brain (cerebellum)
6.0


Lung ca. NCI-H23
29.3
Brain (fetal)
8.4


Lung ca. NCI-H460
14.8
Brain (Hippocampus)
14.5




Pool


Lung ca. HOP-62
19.5
Cerebral Cortex Pool
16.2


Lung ca. NCI-H522
28.7
Brain (Substantia
16.0




nigra) Pool


Liver
0.4
Brain (Thalamus) Pool
22.7


Fetal Liver
11.9
Brain (whole)
5.9


Liver ca. HepG2
12.9
Spinal Cord Pool
16.0


Kidney Pool
18.4
Adrenal Gland
5.1


Fetal Kidney
22.8
Pituitary gland Pool
3.8


Renal ca. 786-0
28.5
Salivary Gland
2.1


Renal ca. A498
5.0
Thyroid (female)
8.2


Renal ca. ACHN
22.4
Pancreatic ca.
51.4




CAPAN 2


Renal ca. UO-31
36.9
Pancreas Pool
12.3










[1180]

698





TABLE JD










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3380, Run

Ag3380, Run


Tissue Name
165296532
Tissue Name
165296532













Secondary Th1 act
13.1
HUVEC IL-1beta
15.0


Secondary Th2 act
14.6
HUVEC IFN gamma
19.6


Secondary Tr1 act
15.2
HUVEC TNF alpha +
28.3




IFN gamma


Secondary Th1 rest
4.6
HUVEC TNF alpha +
26.1




IL4


Secondary Th2 rest
4.7
HUVEC IL-11
7.8


Secondary Tr1 rest
8.0
Lung Microvascular EC
25.5




none


Primary Th1 act
14.9
Lung Microvascular EC
19.5




TNF alpha + IL-1beta


Primary Th2 act
13.2
Microvascular Dermal
37.9




EC none


Primary Tr1 act
20.7
Microsvasular Dermal
24.8




EC TNF alpha + IL-1beta


Primary Th1 rest
35.6
Bronchial epithelium
37.1




TNF alpha + IL1beta


Primary Th2 rest
24.0
Small airway epithelium
15.0




none


Primary Tr1 rest
16.2
Small airway epithelium
100.0




TNF alpha + IL-1beta


CD45RA CD4
23.3
Coronery artery SMC rest
30.1


lymphocyte act


CD45RO CD4
18.2
Coronery artery SMC
13.6


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
7.4
Astrocytes rest
22.5


Secondary CD8
13.4
Astrocytes TNF alpha +
21.2


lymphocyte rest

IL-1beta


Secondary CD8
4.4
KU-812 (Basophil) rest
17.9


lymphocyte act


CD4 lymphocyte none
8.0
KU-812 (Basophil)
68.3




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
10.7
CCD1106
22.1


CD95 CH11

(Keratinocytes) none


LAK cells rest
13.5
CCD1106
9.2




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
12.9
Liver cirrhosis
3.1


LAK cells IL-2 + IL-12
13.2
Lupus kidney
2.9


LAK cells IL-2 + IFN
15.6
NCI-H292 none
48.6


gamma


LAK cells IL-2 + IL-18
17.0
NCI-H292 IL-4
66.9


LAK cells
9.5
NCI-H292 IL-9
59.5


PMA/ionomycin


NK Cells IL-2 rest
7.0
NCI-H292 IL-13
36.6


Two Way MLR 3 day
15.2
NCI-H292 IFN gamma
42.6


Two Way MLR 5 day
7.0
HPAEC none
14.3


Two Way MLR 7 day
9.6
HPAEC TNF alpha + IL-
25.9




1beta


PBMC rest
6.4
Lung fibroblast none
12.5


PBMC PWM
60.7
Lung fibroblast TNF
11.0




alpha + IL-1beta


PBMC PHA-L
18.8
Lung fibroblast IL-4
25.9


Ramos (B cell) none
31.9
Lung fibroblast IL-9
20.6


Ramos (B cell)
94.0
Lung fibroblast IL-13
18.8


ionomycin


B lymphocytes PWM
42.9
Lung fibroblast IFN
23.3




gamma


B lymphocytes CD40L
24.7
Dermal fibroblast
59.5


and IL-4

CCD1070 rest


EOL-1 dbcAMP
12.9
Dermal fibroblast
64.2




CCD1070 TNF alpha


EOL-1 dbcAMP
10.4
Dermal fibroblast
32.8


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
19.6
Dermal fibroblast IFN
10.7




gamma


Dendritic cells LPS
10.7
Dermal fibroblast IL-4
21.6


Dendritic cells anti-
18.8
IBD Colitis 2
2.0


CD40


Monocytes rest
15.0
IBD Crohn's
3.6


Monocytes LPS
13.8
Colon
36.9


Macrophages rest
25.3
Lung
19.3


Macrophages LPS
8.1
Thymus
72.2


HUVEC none
19.9
Kidney
24.5


HUVEC starved
35.8










[1181] CNS_neurodegeneration_v1.0 Summary: Ag3380 This panel does not show differential expression of the CG58590-01 gene in Alzheimer's disease. However, this expression profile confirms the presence of this gene in the brain. Please see Panel 1.3D for discussion of utility of this gene in the central nervous system.


[1182] General_screening_panel_v1.4 Summary: Ag3380—This gene is expressed at low to moderate levels in all samples on this pattern. The highest level of expression is seen in breast cancer cell line T47D (CT=27.8). Based on expression in this panel, this gene may be involved in brain, colon, renal, lung, ovarian and prostate cancer as well as melanomas. Thus, expression of this gene could be used as a diagnostic marker for the presence of these cancers. Furthermore, therapeutic inhibition using antibodies or small molecule drugs might be of use in the treatment of these cancers.


[1183] This gene product is also expressed in adipose, pancreas, adrenal, thyroid, pituitary, skeletal muscle, heart, and fetal liver. This widespread expression in tissues with metabolic function suggests that this gene product may be important for the pathogenesis, diagnosis, and/or treatment of metabolic and endocrine diseases, including obesity and Types 1 and 2 diabetes;. Furthermore, this gene is more highly expressed in fetal (CT=30.9) liver when compared to expression in the adult (CT>35) and may be useful for the differentiation of the fetal and adult sources of this tissue.


[1184] In addition, this gene is expressed at moderate levels in the all regions of the CNS examined. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[1185] Panel 4D Summary: Ag3380—This gene is expressed from moderate to low levels across all of the samples on this panel. The highest expression is seen in small airway epithelium treated with TNFalpha and IL-1beta (CT=28.7). Interestingly, expression is much lower in untreated small airway epithelium (CT=31.5). There is also a significant difference between mononuclear cells treated with PWM (CT=29.5) and untreated cells (CT=32.7). Therefore, expression of this gene can be used to differentiate treated and untreated samples.


[1186] Expression of this gene is detected at a moderate level (CT=30.2) in normal colon (similar levels for colon are seen on panel 1.4 (CT=30.9), but is significantly lower in the IBD Colitis 2 (CT=34.4) and IBD Crohn's (CT=33.5) samples. Therefore, therapies designed with the protein encoded for by this gene may potentially modulate colon function and play a role in the identification and treatment of inflammatory or autoimmune diseases, which effect the colon including Crohn's disease and ulcerative colitis.


[1187] K. CG58572-01 and CG58572-02: Glucosamine-Phosphate N-Acetyltransferase


[1188] Expression of gene CG58572-01 and full length clone CG58572-02 was assessed using the primer-probe set Ag3375, described in Table KA. Results of the RTQ-PCR runs are shown in Tables KB, KC and KD.


[1189] Table KA. Probe Name Ag3375
699TABLE KAProbe Name Ag3375StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-aagaagtggactggagtcagaa-3′2258399ProbeTET-5′-tacattttctccagccatttccccaa-3′-TAMRA2686400Reverse5′-agcagtacaaagaggcctcaa-3′21135401


[1190]

700





TABLE KB










CNS_neurodegeneration_v1.0











Rel. Exp.





(%) Ag3375,

Rel. Exp. (%)



Run

Ag3375, Run


Tissue Name
210154239
Tissue Name
210154239













AD 1 Hippo
17.1
Control (Path) 3
4.8




Temporal Ctx


AD 2 Hippo
19.3
Control (Path) 4
27.5




Temporal Ctx


AD 3 Hippo
7.4
AD 1 Occipital Ctx
11.5


AD 4 Hippo
4.5
AD 2 Occipital Ctx
0.0




(Missing)


AD 5 Hippo
72.2
AD 3 Occipital Ctx
5.9


AD 6 Hippo
53.6
AD 4 Occipital Ctx
12.7


Control 2 Hippo
20.3
AD 5 Occipital Ctx
26.6


Control 4 Hippo
6.8
AD 6 Occipital Ctx
19.8


Control (Path) 3
5.5
Control 1 Occipital
3.2


Hippo

Ctx


AD 1 Temporal
11.6
Control 2 Occipital
36.1


Ctx

Ctx


AD 2 Temporal
23.8
Control 3 Occipital
7.4


Ctx

Ctx


AD 3 Temporal
5.5
Control 4 Occipital
4.1


Ctx

Ctx


AD 4 Temporal
16.5
Control (Path) 1
66.0


Ctx

Occipital Ctx


AD 5 Inf Temporal
100.0
Control (Path) 2
8.2


Ctx

Occipital Ctx


AD 5 Sup
55.9
Control (Path) 3
1.9


Temporal Ctx

Occipital Ctx


AD 6 Inf Temporal
37.9
Control (Path) 4
12.2


Ctx

Occipital Ctx


AD 6 Sup
59.5
Control 1 Parietal
2.4


Temporal Ctx

Ctx


Control 1
3.5
Control 2 Parietal
31.6


Temporal Ctx

Ctx


Control 2
25.3
Control 3 Parietal
11.7


Temporal Ctx

Ctx


Control 3
8.2
Control (Path) 1
49.7


Temporal Ctx

Parietal Ctx


Control 3
4.0
Control (Path) 2
15.4


Temporal Ctx

Parietal Ctx


Control (Path) 1
52.9
Control (Path) 3
4.2


Temporal Ctx

Parietal Ctx


Control (Path) 2
26.6
Control (Path) 4
32.5


Temporal Ctx

Parietal Ctx










[1191]

701





TABLE KC










Panel 1.3D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3375,

Ag3375,


Tissue Name
Run 165674233
Tissue Name
Run 165674233













Liver adenocarcinoma
51.8
Kidney (fetal)
9.7


Pancreas
9.3
Renal ca. 786-0
19.6


Pancreatic ca. CAPAN 2
52.1
Renal ca. A498
26.2


Adrenal gland
8.9
Renal ca. RXF 393
15.7


Thyroid
6.3
Renal ca. ACHN
8.2


Salivary gland
18.3
Renal ca. UO-31
35.4


Pituitary gland
15.1
Renal ca. TK-10
9.8


Brain (fetal)
15.5
Liver
20.4


Brain (whole)
34.6
Liver (fetal)
16.5


Brain (amygdala)
16.0
Liver ca.
49.0




(hepatoblast) HepG2


Brain (cerebellum)
34.2
Lung
4.5


Brain (hippocampus)
12.1
Lung (fetal)
5.4


Brain (substantia nigra)
12.8
Lung ca. (small cell)
32.3




LX-1


Brain (thalamus)
17.9
Lung ca. (small cell)
17.3




NCI-H69


Cerebral Cortex
10.4
Lung ca. (s.cell var.)
30.1




SHP-77


Spinal cord
13.3
Lung ca. (large
66.4




cell)NCI-H460


glio/astro U87-MG
14.8
Lung ca. (non-sm.
19.1




cell) A549


glio/astro U-118-MG
95.3
Lung ca. (non-s.cell)
13.8




NCI-H23


Astrocytoma SW1783
42.0
Lung ca. (non-s.cell)
18.7




HOP-62


neuro*; met SK-N-AS
47.0
Lung ca. (non-s.cl)
19.5




NCI-H522


Astrocytoma SF-539
11.4
Lung ca. (squam.)
9.9




SW 900


Astrocytoma SNB-75
15.6
Lung ca. (squam.)
19.6




NCI-H596


glioma SNB-19
11.8
Mammary gland
14.6


glioma U251
40.9
Breast ca.* (pl.ef)
81.2




MCF-7


glioma SF-295
10.1
Breast ca.* (pl.ef)
91.4




MDA-MB-231


Heart (fetal)
1.3
Breast ca.* (pl.ef)
35.4




T47D


Heart
4.7
Breast ca. BT-549
97.9


Skeletal muscle (fetal)
1.2
Breast ca. MDA-N
14.8


Skeletal muscle
38.7
Ovary
1.6


Bone marrow
4.6
Ovarian ca.
39.2




OVCAR-3


Thymus
2.7
Ovarian ca.
23.0




OVCAR-4


Spleen
7.9
Ovarian ca.
13.8




OVCAR-5


Lymph node
13.0
Ovarian ca.
8.5




OVCAR-8


Colorectal
3.3
Ovarian ca. IGROV-1
5.6


Stomach
27.7
Ovarian ca.*
44.8




(ascites) SK-OV-3


Small intestine
19.3
Uterus
19.5


Colon ca. SW480
16.5
Placenta
2.6


Colon ca.*
29.1
Prostate
15.6


SW620(SW480 met)


Colon ca. HT29
13.8
Prostate ca.* (bone
56.6




met)PC-3


Colon ca. HCT-116
27.7
Testis
40.6


Colon ca. CaCo-2
17.4
Melanoma
5.5




Hs688(A).T


Colon ca.
26.4
Melanoma* (met)
8.9


tissue(ODO3866)

Hs688(B).T


Colon ca. HCC-2998
32.1
Melanoma UACC-
17.8




62


Gastric ca.* (liver met)
100.0
Melanoma M14
27.7


NCI-N87


Bladder
28.7
Melanoma LOX
6.6




IMVI


Trachea
9.4
Melanoma* (met)
13.0




SK-MEL-5


Kidney
9.0
Adipose
8.0










[1192]

702





TABLE KD










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3375, Run

Ag3375, Run


Tissue Name
165296547
Tissue Name
165296547













Secondary Th1 act
14.6
HUVEC IL-1beta
24.5


Secondary Th2 act
13.0
HUVEC IFN gamma
24.5


Secondary Tr1 act
17.3
HUVEC TNF alpha +
24.0




IFN gamma


Secondary Th1 rest
0.9
HUVEC TNF alpha +
23.2




IL4


Secondary Th2 rest
1.5
HUVEC IL-11
12.1


Secondary Tr1 rest
2.9
Lung Microvascular EC
21.3




none


Primary Th1 act
16.0
Lung Microvascular EC
24.1




TNF alpha + IL-1beta


Primary Th2 act
12.1
Microvascular Dermal
27.4




EC none


Primary Tr1 act
25.0
Microsvasular Dermal
24.0




EC TNF alpha + IL-1beta


Primary Th1 rest
10.4
Bronchial epithelium
20.3




TNF alpha + IL1beta


Primary Th2 rest
6.1
Small airway epithelium
11.3




none


Primary Tr1 rest
9.0
Small airway epithelium
54.0




TNF alpha + IL-1beta


CD45RA CD4
14.6
Coronery artery SMC rest
23.5


lymphocyte act


CD45RO CD4
13.6
Coronery artery SMC
12.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
14.2
Astrocytes rest
5.3


Secondary CD8
14.4
Astrocytes TNF alpha +
5.4


lymphocyte rest

IL-1beta


Secondary CD8
5.8
KU-812 (Basophil) rest
19.5


lymphocyte act


CD4 lymphocyte none
2.4
KU-812 (Basophil)
56.3




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
2.6
CCD1106
26.6


CD95 CH11

(Keratinocytes) none


LAK cells rest
5.1
CCD1106
7.8




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
10.7
Liver cirrhosis
2.6


LAK cells IL-2 + IL-12
12.5
Lupus kidney
0.8


LAK cells IL-2 + IFN
20.2
NCI-H292 none
28.7


gamma


LAK cells IL-2 + IL-18
16.6
NCI-H292 IL-4
54.7


LAK cells
12.5
NCI-H292 IL-9
45.7


PMA/ionomycin


NK Cells IL-2 rest
7.1
NCI-H292 IL-13
24.3


Two Way MLR 3 day
6.8
NCI-H292 IFN gamma
33.2


Two Way MLR 5 day
8.9
HPAEC none
17.8


Two Way MLR 7 day
6.0
HPAEC TNF alpha + IL-
30.1




1beta


PBMC rest
0.8
Lung fibroblast none
10.2


PBMC PWM
42.3
Lung fibroblast TNF
6.3




alpha + IL-1beta


PBMC PHA-L
11.6
Lung fibroblast IL-4
27.2


Ramos (B cell) none
30.6
Lung fibroblast IL-9
26.8


Ramos (B cell)
100.0
Lung fibroblast IL-13
21.8


ionomycin


B lymphocytes PWM
77.4
Lung fibroblast IFN
29.5




gamma


B lymphocytes CD40L
12.2
Dermal fibroblast
42.3


and IL-4

CCD1070 rest


EOL-1 dbcAMP
13.0
Dermal fibroblast
51.4




CCD1070 TNF alpha


EOL-1 dbcAMP
6.9
Dermal fibroblast
22.5


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
4.5
Dermal fibroblast IFN
11.1




gamma


Dendritic cells LPS
3.8
Dermal fibroblast IL-4
19.5


Dendritic cells anti-
2.9
IBD Colitis 2
0.7


CD40


Monocytes rest
2.2
IBD Crohn's
0.9


Monocytes LPS
1.3
Colon
7.6


Macrophages rest
6.6
Lung
6.2


Macrophages LPS
2.7
Thymus
9.4


HUVEC none
17.4
Kidney
4.2


HUVEC starved
37.4










[1193] CNS_neurodegeneration_v1.0 Summary: Ag3375 This panel does not show differential expression of the CG58572-01 gene in Alzheimer's disease. However, this expression profile confirms the presence of this gene in the brain. Please see Panel 1.3D for discussion of utility of this gene in the central nervous system.


[1194] Panel 1.3D Summary: Ag3375—This gene is expressed at moderate to low levels in all samples on this panel, with the highest expression in gastric cancer cell line NCI-N87 (CT=28.8). Based on expression in this panel, this gene may be involved in gastric, pancreatic, brain, colon, renal, lung, breast, ovarian and prostate cancer as well as melanomas. Thus, expression of this gene could be used as a diagnostic marker for the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene might be of use in the treatment of these cancers.


[1195] This gene product is also expressed in adipose, pancreas, adrenal, thyroid, pituitary, skeletal muscle, heart, and liver. This widespread expression in tissues with metabolic function suggests that this gene product may be important for the pathogenesis, diagnosis, and/or treatment of metabolic and endocrine diseases, including obesity and Types 1 and 2 diabetes.


[1196] In addition, this gene is expressed at moderate levels in the CNS. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[1197] Panel 4D Summary: Ag3375 The CG58572-01 gene is ubiquitously expressed on this panel, with highest expression in the B cell line Ramos treated with ionomycin (CT=26.2). Significant levels of expression are also seen in pokeweed mitogen-activated B lymphocytes. Therefore, therapies that antagonize the function of this gene product may be useful as therapeutic drugs to reduce or eliminate the symptoms in patients with autoimmune and inflammatory diseases in which B cells play a part in the initiation or progression of the disease process, such as lupus erythematosus, Crohn's disease, ulcerative colitis, multiple sclerosis, chronic obstructive pulmonary disease, asthma, emphysema, rheumatoid arthritis, or psoriasis.


[1198] Interestingly, there is a difference between the levels of expression in resting and activated secondary T cells. The level in activated secondary T cells (CT=28.7-29.2) appears to be higher than in resting T cells (CT=31.3-33.1). Therefore, therapeutics designed with the protein encoded by this transcript could be important in the regulation of T cell function.


[1199] L. CG58564-01 and CG58564-02: Protein Tyrosine Phosphatase


[1200] Expression of gene CG58564-01 and full length clone CG58564-02 was assessed using the primer-probe sets Ag3023 and Ag3373, described in Tables LA and LB. Results of the RTQ-PCR runs are shown in Tables LC, LD, LE and LF.


[1201] Table LA. Probe Name Ag3023
703TABLE LAProbe Name Ag3023StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-ctaatgctggatttgtccatca-3′22492402ProbeTET-5′-tcaggaatatgaagccatctacctagca-3′-TAMRA28517403Reverse5′-tggagtggtgacatcatctgta-3′22555404


[1202] Table LB. Probe Name Ag3373
704TABLE LBProbe Name Ag3373StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-atttgtccatcaacttcaggaa-3′22502405ProbeTET-5′-tgaagccatctacctagcaaaattaaca-3′-TAMRA28526406Reverse5′-tggagtggtgacatcatctgta-3′22555407


[1203]

705





TABLE LC










CNS_neurodegeneration_v1.0













Rel. Exp. (%)
Rel. Exp. (%)

Rel. Exp. (%)
Rel. Exp. (%)



Ag3023, Run
Ag3373, Run
Tissue
Ag3023, Run
Ag3373, Run


Tissue Name
209821074
210154071
Name
209821074
210154071















AD 1 Hippo
10.9
16.8
Control
9.1
8.0





(Path) 3





Temporal





Ctx


AD 2 Hippo
34.2
37.6
Control
40.6
65.5





(Path) 4





Temporal





Ctx


AD 3 Hippo
12.0
15.8
AD 1
24.7
29.1





Occipital





Ctx


AD 4 Hippo
13.8
10.3
AD 2
0.0
0.0





Occipital





Ctx





(Missing)


AD 5 hippo
60.7
57.8
AD 3
14.7
15.0





Occipital





Ctx


AD 6 Hippo
80.7
72.2
AD 4
35.4
22.4





Occipital





Ctx


Control 2
35.8
38.4
AD 5
3.9
30.4


Hippo


Occipital





Ctx


Control 4
16.5
11.7
AD 6
46.0
37.4


Hippo


Occipital





Ctx


Control (Path)
13.1
15.4
Control 1
9.9
10.7


3 Hippo


Occipital





Ctx


AD 1 Temporal
39.0
31.4
Control 2
39.0
38.4


Ctx


Occipital





Ctx


AD 2 Temporal
38.7
73.2
Control 3
23.0
20.6


Ctx


Occipital





Ctx


AD 3 Temporal
9.5
13.2
Control 4
13.3
13.3


Ctx


Occipital





Ctx


AD 4 Temporal
27.9
34.9
Control
80.1
76.3


Ctx


(Path) 1





Occipital





Ctx


AD 5 Inf
59.0
100.0
Control
17.3
20.0


Temporal Ctx


(Path) 2





Occipital





Ctx


AD 5
33.2
44.1
Control
8.4
8.7


SupTemporal


(Path) 3


Ctx


Occipital





Ctx


AD 6 Inf
100.0
73.2
Control
21.2
20.6


Temporal Ctx


(Path) 4





Occipital





Ctx


AD 6 Sup
79.6
80.1
Control 1
12.1
16.3


Temporal Ctx


Parietal Ctx


Control 1
10.2
13.7
Control 2
48.0
40.9


Temporal Ctx


Parietal Ctx


Control 2
41.2
31.9
Control 3
17.9
16.3


Temporal Ctx


Parietal Ctx


Control 3
20.3
20.0
Control
74.7
64.2


Temporal Ctx


(Path) 1





Parietal Ctx


Control 4
9.7
9.9
Control
28.9
59.9


Temporal Ctx


(Path) 2





Parietal Ctx


Control (Path)
59.9
68.3
Control
10.2
9.0


1 Temporal Ctx


(Path) 3





Parietal Ctx


Control (Path)
40.3
41.2
Control
44.8
43.8


2 Temporal Ctx


(Path) 4





Parietal Ctx










[1204]

706





TABLE LD










General_screening_panel_v1.4











Rel.

Rel.



Exp. (%)

Exp. (%)



Ag3373,

Ag3373,



Run

Run


Tissue Name
217043119
Tissue Name
217043119













Adipose
12.0
Renal ca. TK-10
20.3


Melanoma*
30.8
Bladder
23.2


Hs688(A).T


Melanoma*
69.3
Gastric ca. (liver met.)
25.3


Hs688(B).T

NCI-N87


Melanoma* M14
15.0
Gastric ca. KATO III
30.8


Melanoma*
26.6
Colon ca. SW-948
9.7


LOXIMVI


Melanoma* SK-
21.5
Colon ca. SW480
35.1


MEL-5


Squamous cell
33.0
Colon ca.* (SW480
13.9


carcinoma SCC-4

met) SW620


Testis Pool
19.8
Colon ca. HT29
8.5


Prostate ca.* (bone
100.0
Colon ca. HCT-116
36.9


met) PC-3


Prostate Pool
9.2
Colon ca. CaCo-2
42.9


Placenta
3.8
Colon cancer tissue
9.0


Uterus Pool
7.4
Colon ca. SW1116
5.8


Ovarian ca.
28.5
Colon ca. Colo-205
4.3


OVCAR-3


Ovarian ca. SK-
40.3
Colon ca. SW-48
4.2


OV-3


Ovarian ca.
20.0
Colon Pool
20.7


OVCAR-4


Ovarian ca.
35.1
Small Intestine Pool
12.2


OVCAR-5


Ovarian ca.
10.9
Stomach Pool
9.9


IGROV-1


Ovarian ca.
9.2
Bone Marrow Pool
11.6


OVCAR-8


Ovary
9.7
Fetal Heart
20.7


Breast ca. MCF-7
37.6
Heart Pool
10.6


Breast ca. MDA-
37.1
Lymph Node Pool
17.9


MB-231


Breast ca. BT 549
62.4
Fetal Skeletal Muscle
12.3


Breast ca. T47D
61.1
Skeletal Muscle Pool
16.0


Breast ca. MDA-N
10.0
Spleen Pool
11.6


Breast Pool
17.3
Thymus Pool
12.2


Trachea
12.0
CNS cancer
29.1




(glio/astro) U87-MG


Lung
6.7
CNS cancer
69.3




(glio/astro) U-118-MG


Fetal Lung
34.2
CNS cancer
34.9




(neuro; met) SK-N-AS


Lung ca. NCI-N417
5.4
CNS cancer (astro)
19.1




SF-539


Lung ca. LX-1
17.2
CNS cancer (astro)
35.8




SNB-75


Lung ca. NCI-H146
3.0
CNS cancer (glio)
11.3




SNB-19


Lung ca. SHP-77
18.6
CNS cancer (glio) SF-
26.4




295


Lung ca. A549
29.1
Brain (Amygdala)
4.5




Pool


Lung ca. NCI-H526
4.6
Brain (cerebellum)
8.1


Lung ca. NCI-H23
31.6
Brain (fetal)
13.2


Lung ca. NCI-H460
18.2
Brain (Hippocampus)
5.3




Pool


Lung ca. HOP-62
14.1
Cerebral Cortex Pool
5.4


Lung ca. NCI-H522
31.6
Brain (Substantia
4.8




nigra) Pool


Liver
1.2
Brain (Thalamus) Pool
8.0


Fetal Liver
32.3
Brain (whole)
6.2


Liver ca. HepG2
14.6
Spinal Cord Pool
6.6


Kidney Pool
22.1
Adrenal Gland
8.1


Fetal Kidney
26.1
Pituitary gland Pool
3.0


Renal ca. 786-0
28.7
Salivary Gland
4.7


Renal ca. A498
11.3
Thyroid (female)
4.4


Renal ca. ACHN
12.2
Pancreatic ca.
17.3




CAPAN2


Renal ca. UO-31
24.1
Pancreas Pool
17.1










[1205]

707





TABLE LE










Panel 1.3D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3023, Run

Ag3023, Run


Tissue Name
167966931
Tissue Name
167966931













Liver adenocarcinoma
51.1
Kidney (fetal)
26.2


Pancreas
6.1
Renal ca. 786-0
34.2


Pancreatic ca. CAPAN 2
17.7
Renal ca. A498
17.6


Adrenal gland
3.8
Renal ca. RXF 393
17.2


Thyroid
3.0
Renal ca. ACHN
13.5


Salivary gland
3.9
Renal ca. UO-31
0.0


Pituitary gland
3.6
Renal ca. TK-10
23.0


Brain (fetal)
8.1
Liver
11.7


Brain (whole)
8.5
Liver (fetal)
8.0


Brain (amygdala)
6.7
Liver ca.
26.2




(hepatoblast) HepG2


Brain (cerebellum)
15.2
Lung
3.1


Brain (hippocampus)
5.4
Lung (fetal)
11.0


Brain (substantia nigra)
9.0
Lung ca. (small cell)
12.9




LX-1


Brain (thalamus)
4.2
Lung ca. (small cell)
9.9




NCI-H69


Cerebral Cortex
2.0
Lung ca. (s.cell var.)
67.8




SHP-77


Spinal cord
6.9
Lung ca. (large
3.4




cell)NCI-H460


glio/astro U87-MG
28.5
Lung ca. (non-sm.
45.1




cell) A549


glio/astro U-118-MG
46.7
Lung ca. (non-s.cell)
22.7




NCI-H23


astrocytoma SW1783
40.6
Lung ca. (non-s.cell)
25.7




HOP-62


neuro*; met SK-N-AS
27.2
Lung ca. (non-s.cl)
38.2




NCI-H522


astrocytoma SF-539
29.7
Lung ca. (squam.)
27.4




SW 900


astrocytoma SNB-75
35.1
Lung ca. (squam.)
29.9




NCI-H596


glioma SNB-19
15.6
Mammary gland
5.1


glioma U251
37.9
Breast ca.* (pl.ef)
47.0




MCF-7


glioma SF-295
18.4
Breast ca.* (pl.ef)
22.7




MDA-MB-231


Heart (fetal)
2.9
Breast ca.* (pl.ef)
86.5




T47D


Heart
12.9
Breast ca. BT-549
15.9


Skeletal muscle (fetal)
3.4
Breast ca. MDA-N
10.4


Skeletal muscle
36.3
Ovary
2.9


Bone marrow
4.5
Ovarian ca.
26.1




OVCAR-3


Thymus
14.3
Ovarian ca.
16.3




OVCAR-4


Spleen
8.7
Ovarian ca.
83.5




OVCAR-5


Lymph node
11.8
Ovarian ca.
9.3




OVCAR-8


Colorectal
10.4
Ovarian ca. IGROV-1
12.0


Stomach
7.8
Ovarian ca.*
100.0




(ascites) SK-OV-3


Small intestine
5.1
Uterus
4.9


Colon ca. SW480
19.3
Placenta
1.3


Colon ca.*
42.9
Prostate
3.9


SW620(SW480 met)


Colon ca. HT29
9.9
Prostate ca.* (bone
78.5




met)PC-3


Colon ca. HCT-116
26.2
Testis
9.7


Colon ca. CaCo-2
41.5
Melanoma
5.9




Hs688(A).T


Colon ca.
6.3
Melanoma* (met)
14.2


tissue(ODO3866)

Hs688(B).T


Colon ca. HCC-2998
16.0
Melanoma UACC-
14.0




62


Gastric ca.* (liver met)
18.8
Melanoma M14
5.7


NCI-N87


Bladder
30.6
Melanoma LOX
8.8




IMVI


Trachea
3.2
Melanoma* (met)
14.7




SK-MEL-5


Kidney
9.6
Adipose
18.9










[1206]

708





TABLE LF










Panel 4D













Rel.
Rel.

Rel.
Rel.



Exp. (%)
Exp. (%)

Exp. (%)
Exp. (%)



Ag3023,
Ag3373,

Ag3023,
Ag3373,



Run
Run

Run
Run


Tissue Name
164516146
165296617
Tissue Name
164516146
165296617















Secondary Th1 act
18.6
17.9
HUVEC IL-1beta
20.3
18.6


Secondary Th2 act
24.3
28.5
HUVEC IFN
25.3
22.7





gamma


Secondary Tr1 act
22.8
21.8
HUVEC TNF
16.3
18.0





alpha + IFN





gamma


Secondary Th1 rest
7.5
6.8
HUVEC TNF
18.2
13.4





alpha + IL4


Secondary Th2 rest
11.6
9.5
HUVEC IL-11
13.7
9.9


Secondary Tr1 rest
12.1
10.7
Lung
25.7
21.6





Microvascular EC





none


Primary Th1 act
20.7
16.5
Lung
26.2
18.3





Microvascular EC





TNF alpha + IL-





1beta


Primary Th2 act
20.2
19.3
Microvascular
27.5
21.3





Dermal EC none


Primary Tr1 act
23.3
27.7
Microsvasular
20.7
19.9





Dermal EC





TNF alpha + IL-





1beta


Primary Th1 rest
51.1
51.4
Bronchial
13.0
16.3





epithelium





TNF alpha +





IL1beta


Primary Th2 rest
26.2
29.5
Small airway
8.1
8.5





epithelium none


Primary Tr1 rest
23.7
26.1
Small airway
50.3
39.8





epithelium





TNF alpha + IL-





1beta


CD45RA CD4
14.6
11.0
Coronery artery
20.2
18.9


lymphocyte act


SMC rest


CD45RO CD4
25.2
22.4
Coronery artery
12.0
9.8


lymphocyte act


SMC TNF alpha +





IL-1beta


CD8 lymphocyte
20.4
15.8
Astrocytes rest
10.4
11.1


act


Secondary CD8
16.5
19.9
Astrocytes
11.7
9.8


lymphocyte rest


TNF alpha + IL-





1beta


Secondary CD8
13.2
9.3
KU-812
47.6
38.2


lymphocyte act


(Basophil) rest


CD4 lymphocyte
17.1
11.6
KU-812
94.0
92.0


none


(Basophil)





PMA/ionomycin


2ry
18.3
16.6
CCD1106
19.9
13.2


Th1/Th2/Tr1_anti-


(Keratinocytes)


CD95 CH11


none


LAK cells rest
25.5
16.0
CCD1106
6.0
4.8





(Keratinocytes)





TNF alpha + IL-





1beta


LAK cells IL-2
27.2
22.5
Liver cirrhosis
3.1
2.7


LAK cells IL-
27.2
19.3
Lupus kidney
2.1
1.7


2 + IL-12


LAK cells IL-
36.3
34.4
NCI-H292 none
30.1
18.9


2 + IFN gamma


LAK cells IL-2 +
35.1
29.7
NCI-H292 IL-4
33.9
34.6


IL-18


LAK cells
12.4
11.0
NCI-H292 IL-9
40.1
29.1


PMA/ionomycin


NK Cells IL-2 rest
20.0
15.0
NCI-H292 IL-13
16.2
14.2


Two Way MLR 3
24.0
16.7
NCI-H292 IFN
16.6
18.4


day


gamma


Two Way MLR 5
12.9
10.1
HPAEC none
13.6
13.5


day


Two Way MLR 7
11.4
9.5
HPAEC TNF
25.3
25.3


day


alpha + IL-1beta


PBMC rest
13.7
10.5
Lung fibroblast
11.4
14.2





none


PBMC PWM
69.3
66.4
Lung fibroblast
6.1
7.2





TNF alpha + IL-





1beta


PBMC PHA-L
22.8
17.7
Lung fibroblast
28.5
29.1





IL-4


Ramos (B cell)
24.1
19.3
Lung fibroblast
23.0
23.3


none


IL-9


Ramos (B cell)
100.0
100.0
Lung fibroblast
20.6
18.9


ionomycin


IL-13


B lymphocytes
71.7
74.2
Lung fibroblast
39.0
32.5


PWM


IFN gamma


B lymphocytes
29.1
28.7
Dermal fibroblast
33.9
31.0


CD40L and IL-4


CCD1070 rest


EOL-1 dbcAMP
12.1
10.5
Dermal fibroblast
76.8
62.0





CCD1070 TNF





alpha


EOL-1 dbcAMP
14.5
10.9
Dermal fibroblast
20.3
13.9


PMA/ionomycin


CCD1070 IL-





1beta


Dendritic cells
13.2
14.8
Dermal fibroblast
14.2
9.5


none


IFN gamma


Dendritic cells LPS
11.7
8.3
Dermal fibroblast
26.4
20.4





IL-4


Dendritic cells
17.7
12.7
IBD Colitis 2
2.6
2.2


anti-CD40


Monocytes rest
16.7
17.6
IBD Crohn's
2.0
1.9


Monocytes LPS
6.4
5.0
Colon
11.9
10.5


Macrophages rest
23.5
22.8
Lung
13.3
11.2


Macrophages LPS
9.9
7.1
Thymus
14.4
12.9


HUVEC none
20.6
17.9
Kidney
27.5
19.6


HUVEC starved
43.5
38.4










[1207] CNS_neurodegeneration_v1.0 Summary: Ag3023/Ag3373 This panel does not show differential expression of the CG58564-01 gene in Alzheimer's disease. However, this expression profile confirms the presence of this gene in the brain. Please see Panel 1.3D for discussion of utility of this gene in the central nervous system.


[1208] General_screening_panel_v1.4 Summary: Ag3373 Highest expression of the CG58564-01 gene is seen in a prostate cancer cell line (CT=27). Overall, this gene is expressed at moderate levels in the cancer cell lines in this panel. A higher level of expression is observed in clusters of cell lines derived from prostate, brain, melanoma, colon, lung, breast and ovarian cancer when compared to expression in normal prostate, brain, colon, lung, breast and ovary. Thus, this gene could potentially be used as a diagnostic marker of cancer in these tissues. Furthermore, inhibition of the activity of this gene product using small molecule drugs may be effective in the treatment of cancer in these tissues.


[1209] Among tissues with metabolic function, this gene product has moderate levels of expression in adipose, heart, skeletal muscle, adrenal, pituitary, thyroid and pancreas. Thus, this gene product may be a small molecule target for the treatment of endocrine and metabolic diseases, including obesity and Types 1 and 2 diabetes.


[1210] In addition, this gene appears to be differentially expressed in fetal (CT value=29) vs adult liver (CT value=33) and may be useful for differentiation between the two sources of this tissue.


[1211] This gene is also expressed at moderate levels in all central nervous system samples present on this panel. Please see Panel 10.3D for discussion of utility of this gene in the central nervous system.


[1212] Panel 1.3D Summary: Ag3023 The CG58564-01 gene is ubiquitously expressed among the samples on this panel, with highest expression in an ovarian cancer cell line (CT=28.8). Overall, the expression of this gene shows good agreement with panel 1.4. A higher level of expression is observed in prostate, brain, melanoma, colon, lung, pancreatic, breast and ovarian cancer cell lines than the normal prostate, brain, colon, lung, pancreas, breast and ovary. Thus, expression of this gene could be used as a diagnostic marker of cancer in these tissues. Furthermore, inhibition of the activity of this gene product using small molecule drugs may be effective in the treatment of cancer in these tissues.


[1213] Among tissues with metabolic function, expression of this gene is widespread, as in the previous panel. Please see Panel 1.4 for discussion of utility of this gene in metabolic disease.


[1214] This gene represents a phosphatase that is also expressed at low to moderate levels across the CNS. Some phosphatases comprise a family of MAP kinase regulating enzymes, members of which are upregulated in brains subjected to insults such as ischemia and seizure activity. MAP kinases are kown to regulate neurotrophic and neurotoxic pathways. Consequently, agents that modulate the activity of this gene may have utility in attenuating the apoptotic and neurodegenerative processes following brain insults.



REFERENCES

[1215] 1. Wiessner C. The dual specificity phosphatase PAC-1 is transcriptionally induced in the rat brain following transient forebrain ischemia. Brain Res Mol Brain Res February 1995;28(2):353-6


[1216] 2. Boschert U, Muda M, Camps M, Dickinson R, Arkinstall S. Induction of the dual specificity phosphatase PAC1 in rat brain following seizure activity. Neuroreport Sep. 29, 1997;8(14):3077-80


[1217] Panel 4D Summary: Ag3023/Ag3373 The CG585864-01 gene is expressed at high to moderate levels in a wide range of cell types and tissues of significance in the immune response in health and disease. Highest expression of this gene is seen in ionomycin treated Ramos B cells (CT=26.83). Therefore, targeting of this gene product with a small molecule drug or antibody therapeutic may modulate the functions of cells of the immune system as well as resident tissue cells and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, and arthritis, including osteoarthritis and rheumatoid arthritis.


[1218] M. CG58564-03: Dual Specificity Phosphatase


[1219] Expression of gene CG58564-03 was assessed using the primer-probe sets Ag3023, Ag3373 and Ag5847, described in Tables MA, MB and MC. Results of the RTQ-PCR runs are shown in Tables MD, ME, MF, MG and NM.


[1220] Table MA. Probe Name Ag3023
709TABLE MAProbe Name Ag3023StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-ctaatgctggatttgtccatca-3′22261408ProbeTET-5′-tcaggaatatgaagccatctacctagca-3′-TAMRA28230409Reverse5′-tggagtggtgacatcatctgta-3′22198410


[1221] Table MB. Probe Name Ag3373
710TABLE MBProbe Name Ag3373StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-atttgtccatcaacttcaggaa-3′22251411ProbeTET-5′-tgaagccatctacctagcaaaattaaca-3′-TAMRA28221412Reverse5′-tggagtggtgacatcatctgta-3′22198413


[1222] Table MC. Probe Name Ag5847
711TABLE MCProbe Name Ag5847StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-cattccaaatgtttctgtagt-3′21335414ProbeTET-5′-ttcatagcagatgaatatgggcctaagaac-3′-TAMRA30371415Reverse5′-ccacagtgcaaggaagac-3′18457416


[1223]

712





TABLE MD










CNS_neurodegeneration_v1.0













Rel. Exp. (%)
Rel. Exp. (%)

Rel. Exp. (%)
Rel. Exp. (%)



Ag3023, Run
Ag3373, Run
Tissue
Ag3023, Run
Ag3373, Run


Tissue Name
209821074
210154071
Name
209821074
210154071















AD 1 Hippo
10.9
16.8
Control
9.1
8.0





(Path) 3





Temporal





Ctx


AD 2 Hippo
34.2
37.6
Control
40.6
65.5





(Path) 4





Temporal





Ctx


AD 3 Hippo
12.0
15.8
AD 1
24.7
29.1





Occipital





Ctx


AD 4 Hippo
13.8
10.3
AD 2
0.0
0.0





Occipital





Ctx





(Missing)


AD 5 hippo
60.7
57.8
AD 3
14.7
15.0





Occipital





Ctx


AD 6 Hippo
80.7
72.2
AD 4
35.4
22.4





Occipital





Ctx


Control 2
35.8
38.4
AD 5
3.9
30.4


Hippo


Occipital





Ctx


Control 4
16.5
11.7
AD 6
46.0
37.4


Hippo


Occipital





Ctx


Control (Path)
13.1
15.4
Control 1
9.9
10.7


3 Hippo


Occipital





Ctx


AD 1 Temporal
39.0
31.4
Control 2
39.0
38.4


Ctx


Occipital





Ctx


AD 2 Temporal
38.7
73.2
Control 3
23.0
20.6


Ctx


Occipital





Ctx


AD 3 Temporal
9.5
13.2
Control 4
13.3
13.3


Ctx


Occipital





Ctx


AD 4 Temporal
27.9
34.9
Control
80.1
76.3


Ctx


(Path) 1





Occipital





Ctx


AD 5 Inf
59.0
100.0
Control
17.3
20.0


Temporal Ctx


(Path) 2





Occipital





Ctx


AD 5
33.2
44.1
Control
8.4
8.7


SupTemporal


(Path) 3


Ctx


Occipital





Ctx


AD 6 Inf
100.0
73.2
Control
21.2
20.6


Temporal Ctx


(Path) 4





Occipital





Ctx


AD 6 Sup
79.6
80.1
Control 1
12.1
16.3


Temporal Ctx


Parietal Ctx


Control 1
10.2
13.7
Control 2
48.0
40.9


Temporal Ctx


Parietal Ctx


Control 2
41.2
31.9
Control 3
17.9
16.3


Temporal Ctx


Parietal Ctx


Control 3
20.3
20.0
Control
74.7
64.2


Temporal Ctx


(Path) 1





Parietal Ctx


Control 4
9.7
9.9
Control
28.9
59.9


Temporal Ctx


(Path) 2





Parietal Ctx


Control (Path)
59.9
68.3
Control
10.2
9.0


1 Temporal Ctx


(Path) 3





Parietal Ctx


Control (Path)
40.3
41.2
Control
44.8
43.8


2 Temporal Ctx


(Path) 4





Parietal Ctx










[1224]

713





TABLE ME










General_screening_panel_v1.4











Rel. Exp. (%)

Rel. Exp. (%)



Ag3373, Run

Ag3373, Run


Tissue Name
217043119
Tissue Name
217043119













Adipose
12.0
Renal ca. TK-10
20.3


Melanoma*
30.8
Bladder
23.2


Hs688(A).T


Melanoma*
69.3
Gastric ca. (liver met.)
25.3


Hs688(B).T

NCI-N87


Melanoma* M14
15.0
Gastric ca. KATO III
30.8


Melanoma*
26.6
Colon ca. SW-948
9.7


LOXIMVI


Melanoma* SK-
21.5
Colon ca. SW480
35.1


MEL-5


Squamous cell
33.0
Colon ca.* (SW480
13.9


carcinoma SCC-4

met) SW620


Testis Pool
19.8
Colon ca. HT29
8.5


Prostate ca.* (bone
100.0
Colon ca. HCT-116
36.9


met) PC-3


Prostate Pool
9.2
Colon ca. CaCo-2
42.9


Placenta
3.8
Colon cancer tissue
9.0


Uterus Pool
7.4
Colon ca. SW1116
5.8


Ovarian ca.
28.5
Colon ca. Colo-205
4.3


OVCAR-3


Ovarian ca. SK-
40.3
Colon ca. SW-48
4.2


OV-3


Ovarian ca.
20.0
Colon Pool
20.7


OVCAR-4


Ovarian ca.
35.1
Small Intestine Pool
12.2


OVCAR-5


Ovarian ca.
10.9
Stomach Pool
9.9


IGROV-1


Ovarian ca.
9.2
Bone Marrow Pool
11.6


OVCAR-8


Ovary
9.7
Fetal Heart
20.7


Breast ca. MCF-7
37.6
Heart Pool
10.6


Breast ca. MDA-
37.1
Lymph Node Pool
17.9


MB-231


Breast ca. BT 549
62.4
Fetal Skeletal Muscle
12.3


Breast ca. T47D
61.1
Skeletal Muscle Pool
16.0


Breast ca. MDA-N
10.0
Spleen Pool
11.6


Breast Pool
17.3
Thymus Pool
12.2


Trachea
12.0
CNS cancer
29.1




(glio/astro) U87-MG


Lung
6.7
CNS cancer
69.3




(glio/astro) U-118-MG


Fetal Lung
34.2
CNS cancer
34.9




(neuro; met) SK-N-AS


Lung ca. NCI-N417
5.4
CNS cancer (astro) SF-
19.1




539


Lung ca. LX-1
17.2
CNS cancer (astro)
35.8




SNB-75


Lung ca. NCI-H146
3.0
CNS cancer (glio)
11.3




SNB-19


Lung ca. SHP-77
18.6
CNS cancer (glio) SF-
26.4




295


Lung ca. A549
29.1
Brain (Amygdala) Pool
4.5


Lung ca. NCI-H526
4.6
Brain (cerebellum)
8.1


Lung ca. NCI-H23
31.6
Brain (fetal)
13.2


Lung ca. NCI-H460
18.2
Brain (Hippocampus)
5.3




Pool


Lung ca. HOP-62
14.1
Cerebral Cortex Pool
5.4


Lung ca. NCI-H522
31.6
Brain (Substantia
4.8




nigra) Pool


Liver
1.2
Brain (Thalamus) Pool
8.0


Fetal Liver
32.3
Brain (whole)
6.2


Liver ca. HepG2
14.6
Spinal Cord Pool
6.6


Kidney Pool
22.1
Adrenal Gland
8.1


Fetal Kidney
26.1
Pituitary gland Pool
3.0


Renal ca. 786-0
28.7
Salivary Gland
4.7


Renal ca. A498
11.3
Thyroid (female)
4.4


Renal ca. ACHN
12.2
Pancreatic ca.
17.3




CAPAN2


Renal ca. UO-31
24.1
Pancreas Pool
17.1










[1225]

714





TABLE MF










General_screening_panel_v1.5











Rel. Exp. (%)

Rel. Exp. (%)



Ag5847, Run

Ag5847, Run


Tissue Name
247590257
Tissue Name
247590257













Adipose
0.1
Renal ca. TK-10
0.2


Melanoma*
0.1
Bladder
0.1


Hs688(A).T


Melanoma*
0.1
Gastric ca. (liver met.)
0.2


Hs688(B).T

NCI-N87


Melanoma* M14
0.1
Gastric ca. KATO III
0.1


Melanoma*
0.1
Colon ca. SW-948
0.1


LOXIMVI


Melanoma* SK-
0.1
Colon ca. SW480
0.2


MEL-5


Squamous cell
0.2
Colon ca.* (SW480
1.8


carcinoma SCC-4

met) SW620


Testis Pool
0.1
Colon ca. HT29
0.0


Prostate ca.* (bone
0.6
Colon ca. HCT-116
0.2


met) PC-3


Prostate Pool
0.0
Colon ca. CaCo-2
0.0


Placenta
0.0
Colon cancer tissue
0.0


Uterus Pool
0.0
Colon ca. SW1116
0.0


Ovarian ca.
0.2
Colon ca. Colo-205
0.0


OVCAR-3


Ovarian ca. SK-
0.1
Colon ca. SW-48
0.0


OV-3


Ovarian ca.
0.1
Colon Pool
0.1


OVCAR-4


Ovarian ca.
0.2
Small Intestine Pool
0.0


OVCAR-5


Ovarian ca.
0.0
Stomach Pool
0.0


IGROV-1


Ovarian ca.
0.1
Bone Marrow Pool
0.0


OVCAR-8


Ovary
0.1
Fetal Heart
0.1


Breast ca. MCF-7
0.3
Heart Pool
0.0


Breast ca. MDA-
0.2
Lymph Node Pool
0.1


MB-231


Breast ca. BT 549
0.2
Fetal Skeletal Muscle
0.1


Breast ca. T47D
0.2
Skeletal Muscle Pool
0.1


Breast ca. MDA-N
0.1
Spleen Pool
0.1


Breast Pool
0.0
Thymus Pool
0.1


Trachea
0.1
CNS cancer
0.2




(glio/astro) U87-MG


Lung
0.0
CNS cancer
0.5




(glio/astro) U-118-MG


Fetal Lung
0.2
CNS cancer
0.2




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.0
CNS cancer (astro) SF-
0.1




539


Lung ca. LX-1
0.0
CNS cancer (astro)
0.2




SNB-75


Lung ca. NCI-H146
0.0
CNS cancer (glio)
0.1




SNB-19


Lung ca. SHP-77
0.1
CNS cancer (glio) SF-
0.2




295


Lung ca. A549
0.2
Brain (Amygdala) Pool
0.0


Lung ca. NCI-H526
0.0
Brain (cerebellum)
0.0


Lung ca. NCI-H23
0.1
Brain (fetal)
0.1


Lung ca. NCI-H460
0.1
Brain (Hippocampus)
0.0




Pool


Lung ca. HOP-62
0.0
Cerebral Cortex Pool
0.0


Lung ca. NCI-H522
0.1
Brain (Substantia
0.0




nigra) Pool


Liver
0.0
Brain (Thalamus) Pool
0.0


Fetal Liver
0.1
Brain (whole)
0.0


Liver ca. HepG2
0.1
Spinal Cord Pool
0.0


Kidney Pool
0.1
Adrenal Gland
0.0


Fetal Kidney
0.1
Pituitary gland Pool
0.0


Renal ca. 786-0
0.2
Salivary Gland
100.0


Renal ca. A498
0.1
Thyroid (female)
0.0


Renal ca. ACHN
0.1
Pancreatic ca.
0.1




CAPAN2


Renal ca. UO-31
0.1
Pancreas Pool
0.0










[1226]

715





TABLE MG










Panel 1.3D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3023, Run

Ag3023, Run


Tissue Name
167966931
Tissue Name
167966931













Liver adenocarcinoma
51.1
Kidney (fetal)
26.2


Pancreas
6.1
Renal ca. 786-0
34.2


Pancreatic ca. CAPAN 2
17.7
Renal ca. A498
17.6


Adrenal gland
3.8
Renal ca. RXF 393
17.2


Thyroid
3.0
Renal ca. ACHN
13.5


Salivary gland
3.9
Renal ca. UO-31
0.0


Pituitary gland
3.6
Renal ca. TK-10
23.0


Brain (fetal)
8.1
Liver
11.7


Brain (whole)
8.5
Liver (fetal)
8.0


Brain (amygdala)
6.7
Liver ca.
26.2




(hepatoblast) HepG2


Brain (cerebellum)
15.2
Lung
3.1


Brain (hippocampus)
5.4
Lung (fetal)
11.0


Brain (substantia nigra)
9.0
Lung ca. (small cell)
12.9




LX-1


Brain (thalamus)
4.2
Lung ca. (small cell)
9.9




NCI-H69


Cerebral Cortex
2.0
Lung ca. (s.cell var.)
67.8




SHP-77


Spinal cord
6.9
Lung ca. (large
3.4




cell)NCI-H460


Glio/astro U87-MG
28.5
Lung ca. (non-sm.
45.1




cell) A549


Glio/astro U-118-MG
46.7
Lung ca. (non-s.cell)
22.7




NCI-H23


astrocytoma SW1783
40.6
Lung ca. (non-s.cell)
25.7




HOP-62


neuro*; met SK-N-AS
27.2
Lung ca. (non-s.cl)
38.2




NCI-H522


astrocytoma SF-539
29.7
Lung ca. (squam.)
27.4




SW 900


astrocytoma SNB-75
35.1
Lung ca. (squam.)
29.9




NCI-H596


glioma SNB-19
15.6
Mammary gland
5.1


glioma U251
37.9
Breast ca.* (pl.ef)
47.0




MCF-7


glioma SF-295
18.4
Breast ca.* (pl.ef)
22.7




MDA-MB-231


Heart (fetal)
2.9
Breast ca.* (pl.ef)
86.5




T47D


Heart
12.9
Breast ca. BT-549
15.9


Skeletal muscle (fetal)
3.4
Breast ca. MDA-N
10.4


Skeletal muscle
36.3
Ovary
2.9


Bone marrow
4.5
Ovarian ca.
26.1




OVCAR-3


Thymus
14.3
Ovarian ca.
16.3




OVCAR-4


Spleen
8.7
Ovarian ca.
83.5




OVCAR-5


Lymph node
11.8
Ovarian ca.
9.3




OVCAR-8


Colorectal
10.4
Ovarian ca. IGROV-1
12.0


Stomach
7.8
Ovarian ca.*
100.0




(ascites) SK-OV-3


Small intestine
5.1
Uterus
4.9


Colon ca. SW480
19.3
Placenta
1.3


Colon ca.*
42.9
Prostate
3.9


SW620(SW480 met)


Colon ca. HT29
9.9
Prostate ca.* (bone
78.5




met)PC-3


Colon ca. HCT-116
26.2
Testis
9.7


Colon ca. CaCo-2
41.5
Melanoma
5.9




Hs688(A).T


Colon ca.
6.3
Melanoma* (met)
14.2


tissue(ODO3866)

Hs688(B).T


Colon ca. HCC-2998
16.0
Melanoma UACC-
14.0




62


Gastric ca.* (liver met)
18.8
Melanoma M14
5.7


NCI-N87


Bladder
30.6
Melanoma LOX
8.8




IMVI


Trachea
3.2
Melanoma* (met)
14.7




SK-MEL-5


Kidney
9.6
Adipose
18.9










[1227]

716





TABLE MH










Panel 4D













Rel.
Rel.

Rel.
Rel.



Exp. (%)
Exp. (%)

Exp. (%)
Exp. (%)



Ag3023,
Ag3373,

Ag3023,
Ag3373,



Run
Run

Run
Run


Tissue Name
164516146
165296617
Tissue Name
164516146
165296617















Secondary Th1 act
18.6
17.9
HUVEC IL-1beta
20.3
18.6


Secondary Th2 act
24.3
28.5
HUVEC IFN
25.3
22.7





gamma


Secondary Tr1 act
22.8
21.8
HUVEC TNF
16.3
18.0





alpha + IFN





gamma


Secondary Th1 rest
7.5
6.8
HUVEC TNF
18.2
13.4





alpha + IL4


Secondary Th2 rest
11.6
9.5
HUVEC IL-11
13.7
9.9


Secondary Tr1 rest
12.1
10.7
Lung
25.7
21.6





Microvascular EC





none


Primary Th1 act
20.7
16.5
Lung
26.2
18.3





Microvascular EC





TNF alpha + IL-





1beta


Primary Th2 act
20.2
19.3
Microvascular
27.5
21.3





Dermal EC none


Primary Tr1 act
23.3
27.7
Microsvasular
20.7
19.9





Dermal EC





TNF alpha + IL-





1beta


Primary Th1 rest
51.1
51.4
Bronchial
13.0
16.3





epithelium





TNF alpha +





IL1beta


Primary Th2 rest
26.2
29.5
Small airway
8.1
8.5





epithelium none


Primary Tr1 rest
23.7
26.1
Small airway
50.3
39.8





epithelium





TNF alpha + IL-





1beta


CD45RA CD4
14.6
11.0
Coronery artery
20.2
18.9


lymphocyte act


SMC rest


CD45RO CD4
25.2
22.4
Coronery artery
12.0
9.8


lymphocyte act


SMC TNF alpha +





IL-1beta


CD8 lymphocyte
20.4
15.8
Astrocytes rest
10.4
11.1


act


Secondary CD8
16.5
19.9
Astrocytes
11.7
9.8


lymphocyte rest


TNF alpha + IL-





1beta


Secondary CD8
13.2
9.3
KU-812
47.6
38.2


lymphocyte act


(Basophil) rest


CD4 lymphocyte
17.1
11.6
KU-812
94.0
92.0


none


(Basophil)





PMA/ionomycin


2ry
18.3
16.6
CCD1106
19.9
13.2


Th1/Th2/Tr1_anti-


(Keratinocytes)


CD95 CH11


none


LAK cells rest
25.5
16.0
CCD1106
6.0
4.8





(Keratinocytes)





TNF alpha + IL-





1beta


LAK cells IL-2
27.2
22.5
Liver cirrhosis
3.1
2.7


LAK cells IL-
27.2
19.3
Lupus kidney
2.1
1.7


2 + IL-12


LAK cells IL-
36.3
34.4
NCI-H292 none
30.1
18.9


2 + IFN gamma


LAK cells IL-2 +
35.1
29.7
NCI-H292 IL-4
33.9
34.6


IL-18


LAK cells
12.4
11.0
NCI-H292 IL-9
40.1
29.1


PMA/ionomycin


NK Cells IL-2 rest
20.0
15.0
NCI-H292 IL-13
16.2
14.2


Two Way MLR 3
24.0
16.7
NCI-H292 IFN
16.6
18.4


day


gamma


Two Way MLR 5
12.9
10.1
HPAEC none
13.6
13.5


day


Two Way MLR 7
11.4
9.5
HPAEC TNF
25.3
25.3


day


alpha + IL-1beta


PBMC rest
13.7
10.5
Lung fibroblast
11.4
14.2





none


PBMC PWM
69.3
66.4
Lung fibroblast
6.1
7.2





TNF alpha + IL-





1beta


PBMC PHA-L
22.8
17.7
Lung fibroblast
28.5
29.1





IL-4


Ramos (B cell)
24.1
19.3
Lung fibroblast
23.0
23.3


none


IL-9


Ramos (B cell)
100.0
100.0
Lung fibroblast
20.6
18.9


ionomycin


IL-13


B lymphocytes
71.7
74.2
Lung fibroblast
39.0
32.5


PWM


IFN gamma


B lymphocytes
29.1
28.7
Dermal fibroblast
33.9
31.0


CD40L and IL-4


CCD1070 rest


EOL-1 dbcAMP
12.1
10.5
Dermal fibroblast
76.8
62.0





CCD1070 TNF





alpha


EOL-1 dbcAMP
14.5
10.9
Dermal fibroblast
20.3
13.9


PMA/ionomycin


CCD1070 IL-





1beta


Dendritic cells
13.2
14.8
Dermal fibroblast
14.2
9.5


none


IFN gamma


Dendritic cells LPS
11.7
8.3
Dermal fibroblast
26.4
20.4





IL-4


Dendritic cells
17.7
12.7
IBD Colitis 2
2.6
2.2


anti-CD40


Monocytes rest
16.7
17.6
IBD Crohn's
2.0
1.9


Monocytes LPS
6.4
5.0
Colon
11.9
10.5


Macrophages rest
23.5
22.8
Lung
13.3
11.2


Macrophages LPS
9.9
7.1
Thymus
14.4
12.9


HUVEC none
20.6
17.9
Kidney
27.5
19.6


HUVEC starved
43.5
38.4










[1228] CNS_neurodegeneration_v1.0 Summary: Ag3023/Ag3373 This panel does not show differential expression of the CG56804-03 gene, a splice variant of CG56804-01, in Alzheimrer's disease. However, this expression profile confirms the presence of this gene in the brain. Please see Panel 1.3D for discussion of utility of this gene in the central nervous system. Ag5847—This primer pair recognizes only the splice variant CG58564-03. Expression of this variant is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1229] General_screening_panel_v1.4 Summary: Ag3373 Highest expression of the CG56804-03 gene is seen in a prostate cancer cell line (CT=27). Overall, this gene is expressed at moderate levels in the cancer cell lines in this panel. A higher level of expression is observed in clusters of cell lines derived from prostate, brain, melanoma, colon, lung, breast and ovarian cancer when compared to expression in normal prostate, brain, colon, lung, breast and ovary. Thus, this gene could potentially be used as a diagnostic marker of cancer in these tissues. Furthermore, inhibition of the activity of this gene product using small molecule drugs may be effective in the treatment of cancer in these tissues.


[1230] Among tissues with metabolic function, this gene product has moderate levels of expression in adipose, heart, skeletal muscle, adrenal, pituitary, thyroid and pancreas. Thus, this gene product may be a small molecule target for the treatment of endocrine and metabolic diseases, including obesity and Types 1 and 2 diabetes.


[1231] In addition, this gene appears to be differentially expressed in fetal (CT value=29) vs adult liver (CT value=33) and may be useful for differentiation between the two sources of this tissue.


[1232] This gene is also expressed at moderate levels in all central nervous system samples present on this panel. Please see Panel 1.3D for discussion of utility of this gene in the central nervous system.


[1233] General_screening_panel_v1.5 Summary: Ag5847—This primer pair, specific to this splice variant, CG58564-03. Expression of this variant is highest in salivary gland (CT=28.6). Therefore, expression of this gene can be used to differentiate this sample from others on the panel.


[1234] Panel 1.3D Summary: Ag3023 The CG56804-03 gene is ubiquitously expressed among the samples on this panel, with highest expression in an ovarian cancer cell line (CT=28.8). Overall, the expression of this gene shows good agreement with panel 1.4. A higher level of expression is observed in prostate, brain, melanoma, colon, lung, pancreatic, breast and ovarian cancer cell lines than the normal prostate, brain, colon, lung, pancreas, breast and ovary. Thus, expression of this gene could be used as a diagnostic marker of cancer in these tissues. Furthermore, inhibition of the activity of this gene product using small molecule drugs may be effective in the treatment of cancer in these tissues.


[1235] Among tissues with metabolic function, expression of this gene is widespread, as in the previous panel. Please see Panel 1.4 for discussion of utility of this gene in metabolic disease.


[1236] This gene represents a dual specificity phosphatase that is also expressed at low to moderate levels across the CNS. Dual-specificity phosphatases comprise a family of MAP kinase regulating enzymes, members of which are upregulated in brains subjected to insults such as ischemia and seizure activity. MAP kinases are kown to regulate neurotrophic and neurotoxic pathways. Consequently, agents that modulate the activity of this gene may have utility in attenuating the apoptotic and neurodegenerative processes following brain insults.


[1237] Panel 4.1D Summary: Ag5847—This primer pair recognizes a splice variant of CG58564-03. Expression of this variant is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1238] Panel 4D Summary: Ag3023/Ag3373 The CG56804-03 gene is expressed at high to moderate levels in a wide range of cell types and tissues of significance in the immune response in health and disease. Highest expression of this gene is seen in ionomycin treated Ramos 13 cells (CT=26.83). Therefore, targeting of this gene product with a small molecule drug or antibody therapeutic may modulate the functions of cells of the immune system as well as resident tissue cells and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, and arthritis, including osteoarthritis and rheumatoid arthritis.


[1239] N. CG58564-04: Dual Specificity Phosphatase


[1240] Expression of gene CG58564-04, a splice variant of CG58564-01, was assessed using the primer-probe sets Ag3023, Ag3373 and Ag5844, described in Tables NA, NB and NC. Results of the RTQ-PCR runs are shown in Tables ND, NE, NF and NG.


[1241] Table NA. Probe Name Ag3023
717TABLE NAProbe Name Ag3023StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-ctaatgctggatttgtccatca-3′22190417ProbeTET-5′-tcaggaatatgaagccatctacctagca-3′-TAMRA28159418Reverse5′-tggagtggtgacatcatctgta-3′22127419


[1242] Table NB. Probe Name Ag3373
718TABLE NBProbe Name Ag3373StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-atttgtccatcaacttcaggaa-3′22180420ProbeTET-5′-tgaagccatctacctagcaaaattaaca-3′-TAMRA28150421Reverse5′-tggagtggtgacatcatctgta-3′22127422


[1243] Table NC. Probe Name Ag5844
719TABLE NCProbe Name Ag5844StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-ccttagtctaaataactgctg-3′21377423ProbeTET-5′-agtttgcttcaatattttgtcgtatgcata-3′-TAMRA30415424Reverse5′-aggagtggacctaccctat-3′19552425


[1244]

720





TABLE ND










CNS_neurodegeneration_v1.0













Rel. Exp. (%)
Rel. Exp. (%)

Rel. Exp. (%)
Rel. Exp. (%)



Ag3023, Run
Ag3373, Run
Tissue
Ag3023, Run
Ag3373, Run


Tissue Name
209821074
210154071
Name
209821074
210154071















AD 1 Hippo
10.9
16.8
Control
9.1
8.0





(Path) 3





Temporal





Ctx


AD 2 Hippo
34.2
37.6
Control
40.6
65.5





(Path) 4





Temporal





Ctx


AD 3 Hippo
12.0
15.8
AD 1
24.7
29.1





Occipital





Ctx


AD 4 Hippo
13.8
10.3
AD 2
0.0
0.0





Occipital





Ctx





(Missing)


AD 5 hippo
60.7
57.8
AD 3
14.7
15.0





Occipital





Ctx


AD 6 Hippo
80.7
72.2
AD 4
35.4
22.4





Occipital





Ctx


Control 2
35.8
38.4
AD 5
3.9
30.4


Hippo


Occipital





Ctx


Control 4
16.5
11.7
AD 6
46.0
37.4


Hippo


Occipital





Ctx


Control (Path)
13.1
15.4
Control 1
9.9
10.7


3 Hippo


Occipital





Ctx


AD 1 Temporal
39.0
31.4
Control 2
39.0
38.4


Ctx


Occipital





Ctx


AD 2 Temporal
38.7
73.2
Control 3
23.0
20.6


Ctx


Occipital





Ctx


AD 3 Temporal
9.5
13.2
Control 4
13.3
13.3


Ctx


Occipital





Ctx


AD 4 Temporal
27.9
34.9
Control
80.1
76.3


Ctx


(Path) 1





Occipital





Ctx


AD 5 Inf
59.0
100.0
Control
17.3
20.0


Temporal Ctx


(Path) 2





Occipital





Ctx


AD 5
33.2
44.1
Control
8.4
8.7


SupTemporal


(Path) 3


Ctx


Occipital





Ctx


AD 6 Inf
100.0
73.2
Control
21.2
20.6


Temporal Ctx


(Path) 4





Occipital





Ctx


AD 6 Sup
79.6
80.1
Control 1
12.1
16.3


Temporal Ctx


Parietal Ctx


Control 1
10.2
13.7
Control 2
48.0
40.9


Temporal Ctx


Parietal Ctx


Control 2
41.2
31.9
Control 3
17.9
16.3


Temporal Ctx


Parietal Ctx


Control 3
20.3
20.0
Control
74.7
64.2


Temporal Ctx


(Path) 1





Parietal Ctx


Control 4
9.7
9.9
Control
28.9
59.9


Temporal Ctx


(Path) 2





Parietal Ctx


Control (Path)
59.9
68.3
Control
10.2
9.0


1 Temporal Ctx


(Path) 3





Parietal Ctx


Control (Path)
40.3
41.2
Control
44.8
43.8


2 Temporal Ctx


(Path) 4





Parietal Ctx










[1245]

721





TABLE NE










General_screening_panel_v1.4











Rel. Exp. (%)

Rel. Exp. (%)



Ag3373, Run

Ag3373, Run


Tissue Name
217043119
Tissue Name
217043119













Adipose
12.0
Renal ca. TK-10
20.3


Melanoma*
30.8
Bladder
23.2


Hs688(A).T


Melanoma*
69.3
Gastric ca. (liver met.)
25.3


Hs688(B).T

NCI-N87


Melanoma* M14
15.0
Gastric ca. KATO III
30.8


Melanoma*
26.6
Colon ca. SW-948
9.7


LOXIMVI


Melanoma* SK-
21.5
Colon ca. SW480
35.1


MEL-5


Squamous cell
33.0
Colon ca.* (SW480
13.9


carcinoma SCC-4

met) SW620


Testis Pool
19.8
Colon ca. HT29
8.5


Prostate ca.* (bone
100.0
Colon ca. HCT-116
36.9


met) PC-3


Prostate Pool
9.2
Colon ca. CaCo-2
42.9


Placenta
3.8
Colon cancer tissue
9.0


Uterus Pool
7.4
Colon ca. SW1116
5.8


Ovarian ca.
28.5
Colon ca. Colo-205
4.3


OVCAR-3


Ovarian ca. SK-
40.3
Colon ca. SW-48
4.2


OV-3


Ovarian ca.
20.0
Colon Pool
20.7


OVCAR-4


Ovarian ca.
35.1
Small Intestine Pool
12.2


OVCAR-5


Ovarian ca.
10.9
Stomach Pool
9.9


IGROV-1


Ovarian ca.
9.2
Bone Marrow Pool
11.6


OVCAR-8


Ovary
9.7
Fetal Heart
20.7


Breast ca. MCF-7
37.6
Heart Pool
10.6


Breast ca. MDA-
37.1
Lymph Node Pool
17.9


MB-231


Breast ca. BT 549
62.4
Fetal Skeletal Muscle
12.3


Breast ca. T47D
61.1
Skeletal Muscle Pool
16.0


Breast ca. MDA-N
10.0
Spleen Pool
11.6


Breast Pool
17.3
Thymus Pool
12.2


Trachea
12.0
CNS cancer
29.1




(glio/astro) U87-MG


Lung
6.7
CNS cancer
69.3




(glio/astro) U-118-MG


Fetal Lung
34.2
CNS cancer
34.9




(neuro; met) SK-N-AS


Lung ca. NCI-N417
5.4
CNS cancer (astro) SF-
19.1




539


Lung ca. LX-1
17.2
CNS cancer (astro)
35.8




SNB-75


Lung ca. NCI-H146
3.0
CNS cancer (glio)
11.3




SNB-19


Lung ca. SHP-77
18.6
CNS cancer (glio) SF-
26.4




295


Lung ca. A549
29.1
Brain (Amygdala) Pool
4.5


Lung ca. NCI-H526
4.6
Brain (cerebellum)
8.1


Lung ca. NCI-H23
31.6
Brain (fetal)
13.2


Lung ca. NCI-H460
18.2
Brain (Hippocampus)
5.3




Pool


Lung ca. HOP-62
14.1
Cerebral Cortex Pool
5.4


Lung ca. NCI-H522
31.6
Brain (Substantia
4.8




nigra) Pool


Liver
1.2
Brain (Thalamus) Pool
8.0


Fetal Liver
32.3
Brain (whole)
6.2


Liver ca. HepG2
14.6
Spinal Cord Pool
6.6


Kidney Pool
22.1
Adrenal Gland
8.1


Fetal Kidney
26.1
Pituitary gland Pool
3.0


Renal ca. 786-0
28.7
Salivary Gland
4.7


Renal ca. A498
11.3
Thyroid (female)
4.4


Renal ca. ACHN
12.2
Pancreatic ca.
17.3




CAPAN2


Renal ca. UO-31
24.1
Pancreas Pool
17.1










[1246]

722





TABLE NF










Panel 1.3D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3023, Run

Ag3023, Run


Tissue Name
167966931
Tissue Name
167966931













Liver adenocarcinoma
51.1
Kidney (fetal)
26.2


Pancreas
6.1
Renal ca. 786-0
34.2


Pancreatic ca. CAPAN 2
17.7
Renal ca. A498
17.6


Adrenal gland
3.8
Renal ca. RXF 393
17.2


Thyroid
3.0
Renal ca. ACHN
13.5


Salivary gland
3.9
Renal ca. UO-31
0.0


Pituitary gland
3.6
Renal ca. TK-10
23.0


Brain (fetal)
8.1
Liver
11.7


Brain (whole)
8.5
Liver (fetal)
8.0


Brain (amygdala)
6.7
Liver ca.
26.2




(hepatoblast) HepG2


Brain (cerebellum)
15.2
Lung
3.1


Brain (hippocampus)
5.4
Lung (fetal)
11.0


Brain (substantia nigra)
9.0
Lung ca. (small cell)
12.9




LX-1


Brain (thalamus)
4.2
Lung ca. (small cell)
9.9




NCI-H69


Cerebral Cortex
2.0
Lung ca. (s.cell var.)
67.8




SHP-77


Spinal cord
6.9
Lung ca. (large
3.4




cell)NCI-H460


Glio/astro U87-MG
28.5
Lung ca. (non-sm.
45.1




cell) A549


Glio/astro U-118-MG
46.7
Lung ca. (non-s.cell)
22.7




NCI-H23


astrocytoma SW1783
40.6
Lung ca. (non-s.cell)
25.7




HOP-62


neuro*; met SK-N-AS
27.2
Lung ca. (non-s.cl)
38.2




NCI-H522


astrocytoma SF-539
29.7
Lung ca. (squam.)
27.4




SW 900


astrocytoma SNB-75
35.1
Lung ca. (squam.)
29.9




NCI-H596


glioma SNB-19
15.6
Mammary gland
5.1


glioma U251
37.9
Breast ca.* (pl.ef)
47.0




MCF-7


glioma SF-295
18.4
Breast ca.* (pl.ef)
22.7




MDA-MB-231


Heart (fetal)
2.9
Breast ca.* (pl.ef)
86.5




T47D


Heart
12.9
Breast ca. BT-549
15.9


Skeletal muscle (fetal)
3.4
Breast ca. MDA-N
10.4


Skeletal muscle
36.3
Ovary
2.9


Bone marrow
4.5
Ovarian ca.
26.1




OVCAR-3


Thymus
14.3
Ovarian ca.
16.3




OVCAR-4


Spleen
8.7
Ovarian ca.
83.5




OVCAR-5


Lymph node
11.8
Ovarian ca.
9.3




OVCAR-8


Colorectal
10.4
Ovarian ca. IGROV-1
12.0


Stomach
7.8
Ovarian ca.*
100.0




(ascites) SK-OV-3


Small intestine
5.1
Uterus
4.9


Colon ca. SW480
19.3
Placenta
1.3


Colon ca.*
42.9
Prostate
3.9


SW620(SW480 met)


Colon ca. HT29
9.9
Prostate ca.* (bone
78.5




met)PC-3


Colon ca. HCT-116
26.2
Testis
9.7


Colon ca. CaCo-2
41.5
Melanoma
5.9




Hs688(A).T


Colon ca.
6.3
Melanoma* (met)
14.2


tissue(ODO3866)

Hs688(B).T


Colon ca. HCC-2998
16.0
Melanoma UACC-
14.0




62


Gastric ca.* (liver met)
18.8
Melanoma M14
5.7


NCI-N87


Bladder
30.6
Melanoma LOX
8.8




IMVI


Trachea
3.2
Melanoma* (met)
14.7




SK-MEL-5


Kidney
9.6
Adipose
18.9










[1247]

723





TABLE NG










Panel 4D













Rel.
Rel.

Rel.
Rel.



Exp. (%)
Exp. (%)

Exp. (%)
Exp. (%)



Ag3023,
Ag3373,

Ag3023,
Ag3373,



Run
Run

Run
Run


Tissue Name
164516146
165296617
Tissue Name
164516146
165296617















Secondary Th1 act
18.6
17.9
HUVEC IL-1beta
20.3
18.6


Secondary Th2 act
24.3
28.5
HUVEC IFN
25.3
22.7





gamma


Secondary Tr1 act
22.8
21.8
HUVEC TNF
16.3
18.0





alpha + IFN





gamma


Secondary Th1 rest
7.5
6.8
HUVEC TNF
18.2
13.4





alpha + IL4


Secondary Th2 rest
11.6
9.5
HUVEC IL-11
13.7
9.9


Secondary Tr1 rest
12.1
10.7
Lung
25.7
21.6





Microvascular EC





none


Primary Th1 act
20.7
16.5
Lung
26.2
18.3





Microvascular EC





TNF alpha + IL-





1beta


Primary Th2 act
20.2
19.3
Microvascular
27.5
21.3





Dermal EC none


Primary Tr1 act
23.3
27.7
Microsvasular
20.7
19.9





Dermal EC





TNF alpha + IL-





1beta


Primary Th1 rest
51.1
51.4
Bronchial
13.0
16.3





epithelium





TNF alpha +





IL1beta


Primary Th2 rest
26.2
29.5
Small airway
8.1
8.5





epithelium none


Primary Tr1 rest
23.7
26.1
Small airway
50.3
39.8





epithelium





TNF alpha + IL-





1beta


CD45RA CD4
14.6
11.0
Coronery artery
20.2
18.9


lymphocyte act


SMC rest


CD45RO CD4
25.2
22.4
Coronery artery
12.0
9.8


lymphocyte act


SMC TNF alpha +





IL-1beta


CD8 lymphocyte
20.4
15.8
Astrocytes rest
10.4
11.1


act


Secondary CD8
16.5
19.9
Astrocytes
11.7
9.8


lymphocyte rest


TNF alpha + IL-





1beta


Secondary CD8
13.2
9.3
KU-812
47.6
38.2


lymphocyte act


(Basophil) rest


CD4 lymphocyte
17.1
11.6
KU-812
94.0
92.0


none


(Basophil)





PMA/ionomycin


2ry
18.3
16.6
CCD1106
19.9
13.2


Th1/Th2/Tr1_anti-


(Keratinocytes)


CD95 CH11


none


LAK cells rest
25.5
16.0
CCD1106
6.0
4.8





(Keratinocytes)





TNF alpha + IL-





1beta


LAK cells IL-2
27.2
22.5
Liver cirrhosis
3.1
2.7


LAK cells IL-
27.2
19.3
Lupus kidney
2.1
1.7


2 + IL-12


LAK cells IL-
36.3
34.4
NCI-H292 none
30.1
18.9


2 + IFN gamma


LAK cells IL-2 +
35.1
29.7
NCI-H292 IL-4
33.9
34.6


IL-18


LAK cells
12.4
11.0
NCI-H292 IL-9
40.1
29.1


PMA/ionomycin


NK Cells IL-2 rest
20.0
15.0
NCI-H292 IL-13
16.2
14.2


Two Way MLR 3
24.0
16.7
NCI-H292 IFN
16.6
18.4


day


gamma


Two Way MLR 5
12.9
10.1
HPAEC none
13.6
13.5


day


Two Way MLR 7
11.4
9.5
HPAEC TNF
25.3
25.3


day


alpha + IL-1beta


PBMC rest
13.7
10.5
Lung fibroblast
11.4
14.2





none


PBMC PWM
69.3
66.4
Lung fibroblast
6.1
7.2





TNF alpha + IL-





1beta


PBMC PHA-L
22.8
17.7
Lung fibroblast
28.5
29.1





IL-4


Ramos (B cell)
24.1
19.3
Lung fibroblast
23.0
23.3


none


IL-9


Ramos (B cell)
100.0
100.0
Lung fibroblast
20.6
18.9


ionomycin


IL-13


B lymphocytes
71.7
74.2
Lung fibroblast
39.0
32.5


PWM


IFN gamma


B lymphocytes
29.1
28.7
Dermal fibroblast
33.9
31.0


CD40L and IL-4


CCD1070 rest


EOL-1 dbcAMP
12.1
10.5
Dermal fibroblast
76.8
62.0





CCD1070 TNF





alpha


EOL-1 dbcAMP
14.5
10.9
Dermal fibroblast
20.3
13.9


PMA/ionomycin


CCD1070 IL-





1beta


Dendritic cells
13.2
14.8
Dermal fibroblast
14.2
9.5


none


IFN gamma


Dendritic cells LPS
11.7
8.3
Dermal fibroblast
26.4
20.4





IL-4


Dendritic cells
17.7
12.7
IBD Colitis 2
2.6
2.2


anti-CD40


Monocytes rest
16.7
17.6
IBD Crohn's
2.0
1.9


Monocytes LPS
6.4
5.0
Colon
11.9
10.5


Macrophages rest
23.5
22.8
Lung
13.3
11.2


Macrophages LPS
9.9
7.1
Thymus
14.4
12.9


HUVEC none
20.6
17.9
Kidney
27.5
19.6


HUVEC starved
43.5
38.4










[1248] CNS_neurodegeneration_v1.0 Summary: Ag3023/Ag3373 This panel does not show differential expression of the CG56804-04 gene in Alzheimer's disease. However, this expression profile confirms the presence of this gene in the brain. Please see Panel 1.3D for discussion of utility of this gene in the central nervous system. Ag5847—This primer pair recognizes a splice variant of CG58564-01 designated CG58564-04. Expression of this variant is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1249] General_screening_panel_v1.4 Summary: Ag3373 Highest expression of the CG56804-04 gene is seen in a prostate cancer cell line (CT=27). Overall, this gene is expressed at moderate levels in the cancer cell lines in this panel. A higher level of expression is observed in clusters of cell lines derived from prostate, brain, melanoma, colon, lung, breast and ovarian cancer when compared to expression in normal prostate, brain, colon, lung, breast and ovary. Thus, this gene could potentially be used as a diagnostic marker of cancer in these tissues. Furthermore, inhibition of the activity of this gene product using small molecule drugs may be effective in the treatment of cancer in these tissues.


[1250] Among tissues with metabolic function, this gene product has moderate levels of expression in adipose, heart, skeletal muscle, adrenal, pituitary, thyroid and pancreas. Thus, this gene product may be a small molecule target for the treatment of endocrine and metabolic diseases, including obesity and Types 1 and 2 diabetes.


[1251] In addition, this gene appears to be differentially expressed in fetal (CT value=29) vs adult liver (CT value=33) and may be useful for differentiation between the two sources of this tissue.


[1252] This gene is also expressed at moderate levels in all central nervous system samples present on this panel. Please see Panel 1.3D for discussion of utility of this gene in the central nervous system.


[1253] General_screening_panel_v1.5 Summary: Ag5844—This primer pair recognizes a splice variant of CG58564-01. Expression of this variant is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1254] Panel 1.3D Summary: Ag3023 The CG56804-04 gene is ubiquitously expressed among the samples on this panel, with highest expression in an ovarian cancer cell line (CT=28.8). Overall, the expression of this gene shows good agreement with panel 1.4. A higher level of expression is observed in prostate, brain, melanoma, colon, lung, pancreatic, breast and ovarian cancer cell lines than the normal prostate, brain, colon, lung, pancreas, breast and ovary. Thus, expression of this gene could be used as a diagnostic marker of cancer in these tissues. Furthermore, inhibition of the activity of this gene product using small molecule drugs may be effective in the treatment of cancer in these tissues.


[1255] Among tissues with metabolic function, expression of this gene is widespread, as in the previous panel. Please see Panel 1.4 for discussion of utility of this gene in metabolic disease.


[1256] This gene represents a dual specificity phosphatase that is also expressed at low to moderate levels across the CNS. Dual-specificity phosphatases comprise a family of MAP kinase regulating enzymes, members of which are upregulated in brains subjected to insults such as ischemia and seizure activity. MAP kinases are known to regulate neurotrophic and neurotoxic pathways. Consequently, agents that modulate the activity of this gene may have utility in attenuating the apoptotic and neurodegenerative processes following brain insults.


[1257] Panel 41.1D Summary: Ag5844—This primer pair recognizes a splice variant of CG58564-01. Expression of this variant is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1258] Panel 4D Summary: Ag3023/Ag3373 The CG56804-04 gene is expressed at high to moderate levels in a wide range of cell types and tissues of significance in the immune response in health and disease. Highest expression of this gene is seen in ionomycin treated Ramos cells (CT=26.83). Therefore, targeting of ghis gene product with a small molecule drug or antibody therapeutic may modulate the functions of cells of the immune system as well as resident tissue cells and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, and arthritis, including osteoarthritis and rheumatoid arthritis.


[1259] O. CG57819-01: RPGR-Interacting Protein-1


[1260] Expression of gene CG57819-01 was assessed using the primer-probe set Ag3338, described in Table OA. Results of the RTQ-PCR runs are shown in Tables OB and OC.


[1261] Table OA. Probe Name Ag3338
724TABLE OAProbe Name Ag3338StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-cccattcagcactgaaacag-3′203021426ProbeTET-5′-tcctgtaaatgacaaagaatcctctgaaca-3′-TAMRA303055427Reverse5′-tgcttcactgacttcagaacct-3′223085428


[1262]

725





TABLE OB










General_screening_panel_v1.4











Rel. Exp. (%)

Rel. Exp. (%)



Ag3338, Run

Ag3338, Run


Tissue Name
215773746
Tissue Name
215773746













Adipose
1.1
Renal ca. TK-10
0.8


Melanoma*
0.0
Bladder
1.1


Hs688(A).T


Melanoma*
0.0
Gastric ca. (liver met.)
0.0


Hs688(B).T

NCI-N87


Melanoma* M14
0.0
Gastric ca. KATO III
0.0


Melanoma*
0.0
Colon ca. SW-948
0.0


LOXIMVI


Melanoma* SK-
0.2
Colon ca. SW480
0.4


MEL-5


Squamous cell
0.0
Colon ca.* (SW480
0.0


carcinoma SCC-4

met) SW620


Testis Pool
100.0
Colon ca. HT29
0.5


Prostate ca.* (bone
0.0
Colon ca. HCT-116
0.2


met) PC-3


Prostate Pool
1.0
Colon ca. CaCo-2
1.0


Placenta
0.0
Colon cancer tissue
0.9


Uterus Pool
0.0
Colon ca. SW1116
0.2


Ovarian ca.
0.9
Colon ca. Colo-205
0.2


OVCAR-3


Ovarian ca. SK-
0.0
Colon ca. SW-48
0.0


OV-3


Ovarian ca.
1.2
Colon Pool
0.5


OVCAR-4


Ovarian ca.
3.5
Small Intestine Pool
0.3


OVCAR-5


Ovarian ca.
0.0
Stomach Pool
0.2


IGROV-1


Ovarian ca.
0.0
Bone Marrow Pool
0.0


OVCAR-8


Ovary
0.9
Fetal Heart
0.8


Breast ca. MCF-7
1.9
Heart Pool
1.1


Breast ca. MDA-
1.2
Lymph Node Pool
1.4


MB-231


Breast ca. BT 549
0.2
Fetal Skeletal Muscle
0.2


Breast ca. T47D
6.7
Skeletal Muscle Pool
0.0


Breast ca. MDA-N
0.0
Spleen Pool
1.4


Breast Pool
0.5
Thymus Pool
0.0


Trachea
0.9
CNS cancer
0.0




(glio/astro) U87-MG


Lung
0.2
CNS cancer
0.0




(glio/astro) U-118-MG


Fetal Lung
0.4
CNS cancer
0.0




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.0
CNS cancer (astro) SF-
0.0




539


Lung ca. LX-1
0.8
CNS cancer (astro)
0.0




SNB-75


Lung ca. NCI-H146
0.5
CNS cancer (glio)
0.0




SNB-19


Lung ca. SHP-77
0.1
CNS cancer (glio) SF-
0.2




295


Lung ca. A549
1.5
Brain (Amygdala) Pool
0.7


Lung ca. NCI-H526
0.0
Brain (cerebellum)
0.6


Lung ca. NCI-H23
1.5
Brain (fetal)
0.9


Lung ca. NCI-H460
0.0
Brain (Hippocampus)
0.7




Pool


Lung ca. HOP-62
3.0
Cerebral Cortex Pool
0.2


Lung ca. NCI-H522
0.0
Brain (Substantia
0.7




nigra) Pool


Liver
0.4
Brain (Thalamus) Pool
1.3


Fetal Liver
0.5
Brain (whole)
0.0


Liver ca. HepG2
0.2
Spinal Cord Pool
0.9


Kidney Pool
0.9
Adrenal Gland
0.0


Fetal Kidney
0.6
Pituitary gland Pool
0.0


Renal ca. 786-0
0.0
Salivary Gland
0.0


Renal ca. A498
0.0
Thyroid (female)
0.0


Renal ca. ACHN
0.0
Pancreatic ca.
3.4




CAPAN2


Renal ca. UO-31
0.0
Pancreas Pool
0.8










[1263]

726





TABLE OC










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3338, Run

Ag3338, Run


Tissue Name
165221737
Tissue Name
165221737













Secondary Th1 act
0.0
HUVEC IL-1beta
0.0


Secondary Th2 act
0.0
HUVEC IFN gamma
6.9


Secondary Tr1 act
0.0
HUVEC TNF alpha +
0.0




IFN gamma


Secondary Th1 rest
0.0
HUVEC TNF alpha +
0.0




IL4


Secondary Th2 rest
0.0
HUVEC IL-11
0.0


Secondary Tr1 rest
0.0
Lung Microvascular EC
2.6




none


Primary Th1 act
0.0
Lung Microvascular EC
0.0




TNF alpha + IL-1beta


Primary Th2 act
0.0
Microvascular Dermal
1.9




EC none


Primary Tr1 act
0.0
Microsvasular Dermal
0.0




EC TNF alpha + IL-1beta


Primary Th1 rest
0.0
Bronchial epithelium
0.0




TNF alpha + IL1beta


Primary Th2 rest
0.0
Small airway epithelium
0.0




none


Primary Tr1 rest
0.0
Small airway epithelium
0.0




TNF alpha + IL-1beta


CD45RA CD4
0.0
Coronery artery SMC rest
0.0


lymphocyte act


CD45RO CD4
0.0
Coronery artery SMC
0.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
4.0
Astrocytes rest
0.0


Secondary CD8
0.0
Astrocytes TNF alpha +
0.0


lymphocyte rest

IL-1beta


Secondary CD8
0.0
KU-812 (Basophil) rest
0.0


lymphocyte act


CD4 lymphocyte none
0.0
KU-812 (Basophil)
0.0




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
0.0
CCD1106
0.0


CD95 CH11

(Keratinocytes) none


LAK cells rest
4.6
CCD1106
0.0




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
0.0
Liver cirrhosis
0.0


LAK cells IL-2 + IL-12
0.0
Lupus kidney
2.4


LAK cells IL-2 + IFN
0.0
NCI-H292 none
0.0


gamma


LAK cells IL-2 + IL-18
0.0
NCI-H292 IL-4
4.5


LAK cells
3.1
NCI-H292 IL-9
0.0


PMA/ionomycin


NK Cells IL-2 rest
0.0
NCI-H292 IL-13
0.0


Two Way MLR 3 day
0.0
NCI-H292 IFN gamma
0.0


Two Way MLR 5 day
0.0
HPAEC none
0.0


Two Way MLR 7 day
0.0
HPAEC TNF alpha + IL-
0.0




1beta


PBMC rest
14.0
Lung fibroblast none
0.0


PBMC PWM
0.0
Lung fibroblast TNF
0.0




alpha + IL-1beta


PBMC PHA-L
0.0
Lung fibroblast IL-4
0.0


Ramos (B cell) none
3.0
Lung fibroblast IL-9
0.0


Ramos (B cell)
0.0
Lung fibroblast IL-13
0.0


ionomycin


B lymphocytes PWM
0.0
Lung fibroblast IFN
0.0




gamma


B lymphocytes CD40L
0.0
Dermal fibroblast
0.0


and IL-4

CCD1070 rest


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0




CCD1070 TNF alpha


EOL-1 dbcAMP
4.7
Dermal fibroblast
0.0


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
0.0
Dermal fibroblast IFN
0.0




gamma


Dendritic cells LPS
13.9
Dermal fibroblast IL-4
0.0


Dendritic cells anti-
6.0
IBD Colitis 2
0.0


CD40


Monocytes rest
100.0
IBD Crohn's
0.0


Monocytes LPS
0.0
Colon
15.2


Macrophages rest
1.3
Lung
4.0


Macrophages LPS
0.0
Thymus
0.0


HUVEC none
0.0
Kidney
3.1


HUVEC starved
0.0










[1264] CNS_neurodegeneration_v1.0 Summary: Ag3338—Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1265] General_screening_panel_v1.4 Summary: Ag3338—Expression of this gene is highest in testis (CT=29.4). Therefore, expression of this gene could be used to distinguish this sample from others on the panel.


[1266] There is also low expression in pancreatic cancer cell line CAPAN2, lung cancer cell line HOP-62, breast cancer cell line T47D, and ovarian cancer cell line OVCAR-5. Thus, expression of this gene could be used to differentiate these samples from other samples on this panel.


[1267] Panel 4D Summary: Ag3338—Significant expression of this gene is seen only in resting monocytes (CT=32.3) Therefore, expression of this gene can be used to differentiate between this sample and others on this panel.


[1268] P. CG57789-01 and CG57789-02: RAS-Like Protein RRP22-like


[1269] Expression of gene CG57789-01 and variant CG57789-02 was assessed using the primer-probe set Ag3333, described in Table PA. Results of the RTQ-PCR runs are shown in Tables PB, PC and PD.


[1270] Table PA. Probe Name Ag3333
727TABLE PAProbe Name Ag3333StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-tcgactttccacccatcag-3′19181429ProbeTET-5′-cttccctgtcaatacgctccaggagt-3′-TAMRA26203430Reverse5′-aggatgtaggcgtggacact-3′20258431


[1271]

728





TABLE PB










CNS_neurodegeneration_v1.0











Rel. Exp. (%) Ag3333,

Rel. Exp. (%) Ag3333,


Tissue Name
Run 210146459
Tissue Name
Run 210146459













AD 1 Hippo
22.2
Control (Path) 3
7.5




Temporal Ctx


AD 2 Hippo
18.8
Control (Path) 4
21.6




Temporal Ctx


AD 3 Hippo
17.9
AD 1 Occipital Ctx
29.7


AD 4 Hippo
8.7
AD 2 Occipital Ctx
0.0




(Missing)


AD 5 Hippo
100.0
AD 3 Occipital Ctx
15.8


AD 6 Hippo
42.9
AD 4 Occipital Ctx
24.7


Control 2 Hippo
25.9
AD 5 Occipital Ctx
90.1


Control 4 Hippo
12.1
AD 6 Occipital Ctx
16.3


Control (Path) 3
13.4
Control 1 Occipital
4.2


Hippo

Ctx


AD 1 Temporal
21.3
Control 2 Occipital
74.7


Ctx

Ctx


AD 2 Temporal
29.1
Control 3 Occipital
14.5


Ctx

Ctx


AD 3 Temporal
13.3
Control 4 Occipital
4.5


Ctx

Ctx


AD 4 Temporal
15.8
Control (Path) 1
47.3


Ctx

Occipital Ctx


AD 5 Inf Temporal
92.0
Control (Path) 2
13.5


Ctx

Occipital Ctx


AD 5 Sup
43.2
Control (Path) 3
4.1


Temporal Ctx

Occipital Ctx


AD 6 Inf Temporal
26.4
Control (Path) 4
14.6


Ctx

Occipital Ctx


AD 6 Sup
31.6
Control 1 Parietal
7.6


Temporal Ctx

Ctx


Control 1
5.8
Control 2 Parietal
39.2


Temporal Ctx

Ctx


Control 2
51.8
Control 3 Parietal
21.9


Temporal Ctx

Ctx


Control 3
14.5
Control (Path) 1
56.3


Temporal Ctx

Parietal Ctx


Control 3
8.1
Control (Path) 2
20.2


Temporal Ctx

Parietal Ctx


Control (Path) 1
39.2
Control (Path) 3
6.2


Temporal Ctx

Parietal Ctx


Control (Path) 2
40.9
Control (Path) 4
24.5


Temporal Ctx

Parietal Ctx










[1272]

729





TABLE PC










General_screening_panel_v1.4











Rel. Exp. (%)

Rel. Exp. (%)



Ag3333, Run

Ag3333, Run


Tissue Name
216516940
Tissue Name
216516940













Adipose
4.4
Renal ca. TK-10
40.1


Melanoma*
0.9
Bladder
5.0


Hs688(A).T


Melanoma*
1.8
Gastric ca. (liver met.)
4.5


Hs688(B).T

NCI-N87


Melanoma* M14
2.7
Gastric ca. KATO III
20.0


Melanoma*
0.3
Colon ca. SW-948
0.0


LOXIMVI


Melanoma* SK-
0.9
Colon ca. SW480
100.0


MEL-5


Squamous cell
0.1
Colon ca.* (SW480
33.0


carcinoma SCC-4

met) SW620


Testis Pool
2.1
Colon ca. HT29
5.0


Prostate ca.* (bone
2.4
Colon ca. HCT-116
0.1


met) PC-3


Prostate Pool
0.5
Colon ca. CaCo-2
37.1


Placenta
5.7
Colon cancer tissue
2.3


Uterus Pool
0.3
Colon ca. SW1116
16.2


Ovarian ca.
52.9
Colon ca. Colo-205
0.2


OVCAR-3


Ovarian ca. SK-
0.6
Colon ca. SW-48
0.2


OV-3


Ovarian ca.
17.9
Colon Pool
2.2


OVCAR-4


Ovarian ca.
4.5
Small Intestine Pool
1.0


OVCAR-5


Ovarian ca.
0.9
Stomach Pool
0.9


IGROV-1


Ovarian ca.
15.4
Bone Marrow Pool
1.8


OVCAR-8


Ovary
4.2
Fetal Heart
10.9


Breast ca. MCF-7
0.7
Heart Pool
2.8


Breast ca. MDA-
0.4
Lymph Node Pool
4.4


MB-231


Breast ca. BT 549
42.0
Fetal Skeletal Muscle
1.1


Breast ca. T47D
13.0
Skeletal Muscle Pool
46.7


Breast ca. MDA-N
0.1
Spleen Pool
0.0


Breast Pool
2.4
Thymus Pool
2.3


Trachea
2.4
CNS cancer
0.9




(glio/astro) U87-MG


Lung
0.2
CNS cancer
0.3




(glio/astro) U-118-MG


Fetal Lung
0.9
CNS cancer
69.7




(neuro; met) SK-N-AS


Lung ca. NCI-N417
17.1
CNS cancer (astro) SF-
2.2




539


Lung ca. LX-1
1.1
CNS cancer (astro)
15.9




SNB-75


Lung ca. NCI-H146
14.5
CNS cancer (glio)
0.6




SNB-19


Lung ca. SHP-77
37.6
CNS cancer (glio) SF-
6.0




295


Lung ca. A549
0.4
Brain (Amygdala) Pool
28.5


Lung ca. NCI-H526
23.5
Brain (cerebellum)
29.1


Lung ca. NCI-H23
8.2
Brain (fetal)
21.3


Lung ca. NCI-H460
14.3
Brain (Hippocampus)
27.7




Pool


Lung ca. HOP-62
1.7
Cerebral Cortex Pool
36.1


Lung ca. NCI-H522
86.5
Brain (Substantia
40.1




nigra) Pool


Liver
1.6
Brain (Thalamus) Pool
37.6


Fetal Liver
0.7
Brain (whole)
59.5


Liver ca. HepG2
6.2
Spinal Cord Pool
12.3


Kidney Pool
3.8
Adrenal Gland
4.7


Fetal Kidney
7.4
Pituitary gland Pool
3.7


Renal ca. 786-0
0.2
Salivary Gland
48.0


Renal ca. A498
20.9
Thyroid (female)
1.1


Renal ca. ACHN
8.5
Pancreatic ca.
0.0




CAPAN2


Renal ca. UO-31
3.0
Pancreas Pool
4.0










[1273]

730





TABLE PD










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3333, Run

Ag3333, Run


Tissue Name
165084139
Tissue Name
165084139













Secondary Th1 act
0.8
HUVEC IL-1beta
0.0


Secondary Th2 act
3.0
HUVEC IFN gamma
0.5


Secondary Tr1 act
0.6
HUVEC TNF alpha +
0.8




IFN gamma


Secondary Th1 rest
0.0
HUVEC TNF alpha +
0.0




IL4


Secondary Th2 rest
0.5
HUVEC IL-11
0.3


Secondary Tr1 rest
0.0
Lung Microvascular EC
0.6




none


Primary Th1 act
5.7
Lung Microvascular EC
0.4




TNF alpha + IL-1beta


Primary Th2 act
9.8
Microvascular Dermal
0.0




EC none


Primary Tr1 act
3.8
Microsvasular Dermal
0.4




EC TNF alpha + IL-1beta


Primary Th1 rest
0.0
Bronchial epithelium
1.1




TNF alpha + IL1beta


Primary Th2 rest
0.4
Small airway epithelium
1.9




none


Primary Tr1 rest
0.6
Small airway epithelium
1.4




TNF alpha + IL-1beta


CD45RA CD4
4.1
Coronery artery SMC rest
1.7


lymphocyte act


CD45RO CD4
1.7
Coronery artery SMC
1.2


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
1.4
Astrocytes rest
100.0


Secondary CD8
7.4
Astrocytes TNF alpha +
59.9


lymphocyte rest

IL-1beta


Secondary CD8
0.0
KU-812 (Basophil) rest
2.0


lymphocyte act


CD4 lymphocyte none
0.8
KU-812 (Basophil)
4.1




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
0.5
CCD1106
12.5


CD95 CH11

(Keratinocytes) none


LAK cells rest
0.5
CCD1106
6.2




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
0.3
Liver cirrhosis
0.9


LAK cells IL-2 + IL-12
0.5
Lupus kidney
3.9


LAK cells IL-2 + IFN
0.0
NCI-H292 none
29.3


gamma


LAK cells IL-2 + IL-18
0.6
NCI-H292 IL-4
39.5


LAK cells
0.3
NCI-H292 IL-9
23.3


PMA/ionomycin


NK Cells IL-2 rest
0.0
NCI-H292 IL-13
21.9


Two Way MLR 3 day
0.8
NCI-H292 IFN gamma
14.5


Two Way MLR 5 day
0.9
HPAEC none
0.5


Two Way MLR 7 day
0.0
HPAEC TNF alpha + IL-
0.0




1beta


PBMC rest
0.0
Lung fibroblast none
4.5


PBMC PWM
8.1
Lung fibroblast TNF
2.2




alpha + IL-1beta


PBMC PHA-L
11.6
Lung fibroblast IL-4
12.9


Ramos (B cell) none
0.0
Lung fibroblast IL-9
9.2


Ramos (B cell)
0.0
Lung fibroblast IL-13
8.5


ionomycin


B lymphocytes PWM
15.4
Lung fibroblast IFN
8.4




gamma


B lymphocytes CD40L
2.1
Dermal fibroblast
40.6


and IL-4

CCD1070 rest


EOL-1 dbcAMP
0.0
Dermal fibroblast
20.9




CCD1070 TNF alpha


EOL-1 dbcAMP
0.0
Dermal fibroblast
19.3


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
0.0
Dermal fibroblast IFN
1.8




gamma


Dendritic cells LPS
0.5
Dermal fibroblast IL-4
3.8


Dendritic cells anti-
0.0
IBD Colitis 2
0.0


CD40


Monocytes rest
0.0
IBD Crohn's
2.5


Monocytes LPS
0.0
Colon
4.2


Macrophages rest
0.0
Lung
9.1


Macrophages LPS
0.0
Thymus
11.3


HUVEC none
0.4
Kidney
2.6


HUVEC starved
0.6










[1274] CNS_neurodegeneration_v1.0 Summary: This panel confirms the expression of this gene in the brain in an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.


[1275] General_screening_panel_v1.4 Summary: Ag3333 This gene is expressed at moderate to low levels in many of the samples on this panel, with the highest expression in colon cancer cell line SW480 (CT=27.8). Expression is significantly lower in SW680, a cell line derived from a metastasis of the primary tumor represented by SW480. Thus, expression of this gene could be used to differentiate between these two cell lines and potentially between primary colon cancer and its metastases.


[1276] Based on expression in this panel, this gene may be involved in gastric, brain, colon, renal, lung, breast, ovarian and prostate cancer as well as melanomas. Thus, expression of this gene could be used as a diagnostic marker for the presence of these cancers. Furthermore, therapeutic inhibition using antibodies or small molecule drugs might be of use in the treatment of these cancers.


[1277] This gene product is also expressed in adipose, pancreas, adrenal, thyroid, pituitary, skeletal muscle, heart, and liver. This widespread expression in tissues with metabolic function suggests that this gene product may be important for the pathogenesis, diagnosis, and/or treatment of metabolic and endocrine diseases, including obesity and Types 1 and 2 diabetes


[1278] This gene is expressed at low levels throughout the CNS, including in amygdala, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[1279] Panel 4D Summary: Ag3333 The CG57789-01 gene is expressed at moderate to low levels in several samples on this panel, with the highest expression in resting astrocytes (CT=28.4). Moderate expression of this gene is seen in treated and untreated dermal and lung fibroblasts and the airway epithelial tumor line NCI-H292 cells. Thus, the transcript or the protein it encodes may be involved in pathological and inflammatory skin and lung conditions, including psoriasis, asthma, allergy, emphysema, and COPD.


[1280] Q. CG57758-01 and CG57758-02: Sodium/Lithium-Dependent Dicarboxylate Transporter


[1281] Expression of gene CG57758-01, a splice variant of CG57758-02, and CG57758-02 was assessed using the primer-probe sets Ag3326 and Ag3692, described in Tables QA and QB. Results of the RTQ-PCR runs are shown in Tables QC, QD, QE and QF.


[1282] Table QA. Probe Name Ag3326
731TABLE QAProbe Name Ag3326StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-ccatttactggtgcacagaagt-3′22149432ProbeTET-5′-atccctctggctgtcacctctctcat-3′-TAMRA26172433Reverse5′-ggagtccagaatctggaagagt-3′22216434


[1283] Table QB. Probe Name Ag3692
732TABLE QBProbe Name Ag3692StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-ccatttactggtgcacagaagt-3′22149435ProbeTET-5′-atccctctggctgtcacctctctcat-3′-TAMRA26172436Reverse5′-ggagtccagaatctggaagagt-3′22216437


[1284]

733



















Rel.
Rel.
Rel.

Rel.
Rel.
Rel.



Exp. (%)
Exp. (%)
Exp. (%)

Exp. (%)
Exp. (%)
Exp. (%)



Ag3326,
Ag3692,
Ag3692,

Ag3326,
Ag3692,
Ag3692,


Tissue
Run
Run
Run
Tissue
Run
Run
Run


Name
210144197
211145262
224337942
Name
210144197
211145262
224337942






















AD 1
2.1
4.3
1.0
Control
8.5
15.3
12.0


Hippo



(Path) 3






Temporal






Ctx


AD 2
20.9
28.3
25.0
Control
31.2
36.6
52.1


Hippo



(Path) 4






Temporal






Ctx


AD 3
0.0
0.9
0.6
AD 1
2.7
3.0
0.0


Hippo



Occipital






Ctx


AD 4
2.1
7.1
2.6
AD 2
0.0
0.0
0.0


Hippo



Occipital






Ctx






(Missing)


AD 5
72.7
97.9
85.3
AD 3
1.5
7.2
1.3


hippo



Occipital






Ctx


AD 6
13.7
18.3
5.5
AD 4
71.7
35.6
30.6


Hippo



Occipital






Ctx


Control 2
14.5
20.2
15.2
AD 5
25.3
31.9
12.4


Hippo



Occipital






Ctx


Control 4
11.7
7.4
5.1
AD 6
17.2
19.1
11.2


Hippo



Occipital






Ctx


Control
6.7
4.4
4.5
Control 1
7.0
9.0
8.1


(Path) 3



Occipital


Hippo



Ctx


AD 1
4.0
1.7
2.8
Control 2
33.2
44.8
26.1


Temporal



Occipital


Ctx



Ctx


AD 2
80.7
50.7
37.4
Control 3
30.1
37.6
21.9


Temporal



Occipital


Ctx



Ctx


AD 3
3.6
0.0
1.1
Control 4
16.3
12.6
8.2


Temporal



Occipital


Ctx



Ctx


AD 4
19.5
30.6
15.2
Control
42.0
55.9
52.9


Temporal



(Path) 1


Ctx



Occipital






Ctx


AD 5 Inf
100.0
100.0
99.3
Control
6.7
13.0
7.7


Temporal



(Path) 2


Ctx



Occipital






Ctx


AD 5
32.8
29.1
33.2
Control
8.7
6.6
5.4


SupTemporal



(Path) 3


Ctx



Occipital






Ctx


AD 6 Inf
27.7
21.3
26.6
Control
8.1
9.0
7.4


Temporal



(Path) 4


Ctx



Occipital






Ctx


AD 6 Sup
41.8
53.6
17.0
Control 1
21.2
23.0
15.3


Temporal



Parietal


Ctx



Ctx


Control 1
12.0
33.9
18.3
Control 2
48.6
38.2
22.1


Temporal



Parietal


Ctx



Ctx


Control 2
30.1
49.3
44.4
Control 3
28.3
34.4
32.8


Temporal



Parietal


Ctx



Ctx


Control 3
38.7
39.5
33.4
Control
78.5
97.3
100.0


Temporal



(Path) 1


Ctx



Parietal






Ctx


Control 4
17.6
25.2
24.1
Control
50.7
50.7
37.9


Temporal



(Path) 2


Ctx



Parietal






Ctx


Control
69.7
70.7
49.7
Control
10.7
10.1
9.6


(Path) 1



(Path) 3


Temporal



Parietal


Ctx



Ctx


Control
35.4
50.7
33.4
Control
30.6
24.5
40.9


(Path) 2



(Path) 4


Temporal



Parietal


Ctx



Ctx










[1285]

734





TABLE QD










General_screening_panel_v1.4













Rel. Exp. (%)
Rel. Exp. (%)

Rel. Exp. (%)
Rel. Exp. (%)



Ag3326, Run
Ag3692, Run

Ag3326, Run
Ag3692, Run


Tissue Name
215678613
217131191
Tissue Name
215678613
217131191















Adipose
0.0
0.0
Renal ca. TK-10
11.4
12.0


Melanoma*
0.0
0.0
Bladder
0.0
0.1


Hs688(A).T


Melanoma*
0.1
0.0
Gastric ca. (liver
0.0
0.0


Hs688(B).T


met.) NCI-N87


Melanoma*
0.0
0.0
Gastric ca.
0.0
0.0


M14


KATO III


Melanoma*
0.0
0.0
Colon ca. SW-
0.0
0.0


LOXIMVI


948


Melanoma*
0.0
0.0
Colon ca.
0.0
0.0


SK-MEL-5


SW480


Squamous
0.9
0.7
Colon ca.*
0.0
0.0


cell


(SW480 met)


carcinoma


SW620


SCC-4


Testis Pool
0.1
0.2
Colon ca. HT29
0.0
0.0


Prostate ca.*
0.0
0.0
Colon ca. HCT-
0.0
0.0


(bone met)


116


PC-3


Prostate Pool
0.0
0.0
Colon ca. CaCo-2
0.0
0.0


Placenta
0.0
0.0
Colon cancer
0.1
0.0





tissue


Uterus Pool
0.0
0.0
Colon ca.
0.0
0.0





SW1116


Ovarian ca.
0.0
0.0
Colon ca. Colo-
0.0
0.0


OVCAR-3


205


Ovarian ca.
0.0
0.0
Colon ca. SW-48
0.0
0.0


SK-OV-3


Ovarian ca.
0.1
0.0
Colon Pool
0.6
0.0


OVCAR-4


Ovarian ca.
0.0
0.0
Small Intestine
0.1
0.0


OVCAR-5


Pool


Ovarian ca.
0.0
0.0
Stomach Pool
0.0
0.0


IGROV-1


Ovarian ca.
2.8
2.2
Bone Marrow
0.0
0.1


OVCAR-8


Pool


Ovary
0.7
0.6
Fetal Heart
0.0
0.0


Breast ca.
0.0
0.0
Heart Pool
0.0
0.0


MCF-7


Breast ca.
0.0
0.0
Lymph Node
0.1
0.0


MDA-MB-


Pool


231


Breast ca. BT
0.6
0.8
Fetal Skeletal
0.0
0.0


549


Muscle


Breast ca.
0.0
0.0
Skeletal Muscle
0.0
0.0


T47D


Pool


Breast ca.
0.0
0.0
Spleen Pool
0.4
0.2


MDA-N


Breast Pool
0.0
0.1
Thymus Pool
0.0
0.0


Trachea
0.2
0.1
CNS cancer
0.0
0.0





(glio/astro) U87-





MG


Lung
0.0
0.0
CNS cancer
0.0
0.0





(glio/astro) U-





118-MG


Fetal Lung
0.2
0.1
CNS cancer
0.0
0.0





(neuro; met) SK-





N-AS


Lung ca.
0.0
0.0
CNS cancer
0.0
0.0


NCI-N417


(astro) SF-539


Lung ca. LX-1
0.0
0.0
CNS cancer
0.0
0.0





(astro) SNB-75


Lung ca.
0.0
0.0
CNS cancer
0.0
0.0


NCI-H146


(glio) SNB-19


Lung ca.
0.0
0.0
CNS cancer
0.1
0.1


SHP-77


(glio) SF-295


Lung ca.
0.0
0.1
Brain
0.4
0.4


A549


(Amygdala) Pool


Lung ca.
2.0
0.0
Brain
1.4
1.0


NCI-H526


(cerebellum)


Lung ca.
0.7
0.6
Brain (fetal)
0.7
0.4


NCI-H23


Lung ca.
0.0
0.0
Brain
0.5
0.7


NCI-H460


(Hippocampus)





Pool


Lung ca.
0.1
0.2
Cerebral Cortex
1.4
1.5


HOP-62


Pool


Lung ca.
0.0
0.0
Brain (Substantia
1.4
1.4


NCI-H522


nigra) Pool


Liver
28.7
24.1
Brain
1.1
0.9





(Thalamus) Pool


Fetal Liver
100.0
100.0
Brain (whole)
4.1
3.7


Liver ca.
29.5
26.2
Spinal Cord Pool
0.1
0.2


HepG2


Kidney Pool
0.0
0.0
Adrenal Gland
2.6
1.9


Fetal Kidney
0.1
0.1
Pituitary gland
0.0
0.2





Pool


Renal ca.
0.0
0.0
Salivary Gland
40.9
35.1


786-0


Renal ca.
0.0
0.0
Thyroid (female)
0.0
0.0


A498


Renal ca.
0.0
0.0
Pancreatic ca.
0.5
0.8


ACHN


CAPAN2


Renal ca.
0.0
0.0
Pancreas Pool
0.0
0.0


UO-31










[1286]

735





TABLE QE










Panel 4.1D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3692, Run

Ag3692, Run


Tissue Name
169987356
Tissue Name
169987356













Secondary Th1 act
0.0
HUVEC IL-1beta
0.0


Secondary Th2 act
0.0
HUVEC IFN gamma
0.0


Secondary Tr1 act
0.0
HUVEC TNF alpha +
0.0




IFN gamma


Secondary Th1 rest
0.0
HUVEC TNF alpha +
0.0




IL4


Secondary Th2 rest
0.0
HUVEC IL-11
0.0


Secondary Tr1 rest
0.0
Lung Microvascular EC
0.0




none


Primary Th1 act
0.0
Lung Microvascular EC
0.0




TNF alpha + IL-1beta


Primary Th2 act
0.0
Microvascular Dermal
11.3




EC none


Primary Tr1 act
4.2
Microsvasular Dermal
0.0




EC TNF alpha + IL-1beta


Primary Th1 rest
0.0
Bronchial epithelium
28.5




TNF alpha + IL1beta


Primary Th2 rest
0.0
Small airway epithelium
5.7




none


Primary Tr1 rest
0.0
Small airway epithelium
0.0




TNF alpha + IL-1beta


CD45RA CD4
3.9
Coronery artery SMC rest
0.0


lymphocyte act


CD45RO CD4
0.0
Coronery artery SMC
0.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
0.0
Astrocytes rest
0.0


Secondary CD8
0.0
Astrocytes TNF alpha +
0.0


lymphocyte rest

IL-1beta


Secondary CD8
0.0
KU-812 (Basophil) rest
3.6


lymphocyte act


CD4 lymphocyte none
0.0
KU-812 (Basophil)
4.3




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
0.0
CCD1106
10.7


CD95 CH11

(Keratinocytes) none


LAK cells rest
0.0
CCD1106
0.0




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
0.0
Liver cirrhosis
94.0


LAK cells IL-2 + IL-12
0.0
NCI-H292 none
0.0


LAK cells IL-2 + IFN
0.0
NCI-H292 IL-4
0.0


gamma


LAK cells IL-2 + IL-18
0.0
NCI-H292 IL-9
0.0


LAK cells
0.0
NCI-H292 IL-13
0.0


PMA/ionomycin


NK Cells IL-2 rest
0.0
NCI-H292 IFN gamma
0.0


Two Way MLR 3 day
0.0
HPAEC none
0.0


Two Way MLR 5 day
3.2
HPAEC TNF alpha + IL-
0.0




1beta


Two Way MLR 7 day
0.0
Lung fibroblast none
0.0


PBMC rest
0.0
Lung fibroblast TNF
0.0




alpha + IL-1beta


PBMC PWM
0.0
Lung fibroblast IL-4
0.0


PBMC PHA-L
0.0
Lung fibroblast IL-9
0.0


Ramos (B cell) none
0.0
Lung fibroblast IL-13
0.0


Ramos (B cell)
0.0
Lung fibroblast IFN
0.0


ionomycin

gamma


B lymphocytes PWM
0.0
Dermal fibroblast
0.0




CCD1070 rest


B lymphocytes CD40L
0.0
Dermal fibroblast
0.0


and IL-4

CCD1070 TNF alpha


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0




CCD1070 IL-1beta


EOL-1 dbcAMP
0.0
Dermal fibroblast IFN
0.0


PMA/ionomycin

gamma


Dendritic cells none
0.0
Dermal fibroblast IL-4
0.0


Dendritic cells LPS
0.0
Dermal Fibroblasts rest
0.0


Dendritic cells anti-
0.0
Neutrophils TNFa + LPS
0.0


CD40


Monocytes rest
0.0
Neutrophils rest
0.0


Monocytes LPS
0.0
Colon
0.0


Macrophages rest
0.0
Lung
0.0


Macrophages LPS
0.0
Thymus
2.4


HUVEC none
0.0
Kidney
100.0


HUVEC starved
0.0










[1287]

736





TABLE QF










Panel 5 Islet











Rel. Exp. (%)

Rel. Exp. (%)



Ag3326, Run

Ag3326, Run


Tissue Name
242385365
Tissue Name
242385365













97457_Patient-
0.0
94709_Donor 2 AM - A_adipose
0.2


02go_adipose


97476_Patient-
0.0
94710_Donor 2 AM - B_adipose
0.0


07sk_skeletal muscle


97477_Patient-
0.0
94711_Donor 2 AM - C_adipose
0.0


07ut_uterus


97478_Patient-
0.0
94712_Donor 2 AD - A_adipose
0.0


07pl_placenta


99167_Bayer Patient 1
0.3
94713_Donor 2 AD - B_adipose
0.0


97482_Patient-
0.0
94714_Donor 2 AD - C_adipose
0.0


08ut_uterus


97483_Patient-
0.0
94742_Donor 3 U -
0.0


08pl_placenta

A_Mesenchymal Stem Cells


97486_Patient-
0.0
94743_Donor 3 U -
0.0


09sk_skeletal muscle

B_Mesenchymal Stem Cells


97487_Patient-
0.0
94730_Donor 3 AM - A_adipose
0.0


09ut_uterus


97488_Patient-
0.0
94731_Donor 3 AM - B_adipose
0.0


09pl_placenta


97492_Patient-
0.0
94732_Donor 3 AM - C_adipose
0.0


10ut_uterus


97493_Patient-
0.0
94733_Donor 3 AD - A_adipose
0.0


10pl_placenta


97495_Patient-
0.0
94734_Donor 3 AD - B_adipose
0.0


11go_adipose


97496_Patient-
0.0
94735_Donor 3 AD - C_adipose
0.0


11sk_skeletal muscle


97497_Patient-
0.0
77138_Liver_HepG2untreated
100.0


11ut_uterus


97498_Patient-
0.0
73556_Heart_Cardiac stromal
0.0


11pl_placenta

cells (primary)


97500_Patient-
0.1
81735_Small Intestine
39.5


12go_adipose


97501_Patient-
0.3
72409_Kidney_Proximal
0.0


12sk_skeletal muscle

Convoluted Tubule


97502_Patient-
0.0
82685_Small
0.0


12ut_uterus

intestine_Duodenum


97503_Patient-
0.0
90650_Adrenal_Adrenocortical
0.0


12pl_placenta

adenoma


94721_Donor 2 U -
0.0
72410_Kidney_HRCE
0.0


A_Mesenchymal


Stem Cells


94722_Donor 2 U -
0.0
72411_Kidney_HRE
0.0


B_Mesenchymal


Stem Cells


94723_Donor 2 U -
0.0
73139_Uterus_Uterine smooth
0.0


C_Mesenchymal

muscle cells


Stem Cells










[1288] CNS_neurodegeneration_v1.0 Summary: Ag3326/Ag3692—Three experiments done with two primer pairs (same sequence) are in excellent agreement. This panel confirms the expression of this gene at low levels in the brain in an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.


[1289] General_screening_panel_v1.4 Summary: Ag3326/Ag3692 Two experiments with the smae probe and primer set produce results that are in excellent agreement. This gene is highly expressed in fetal liver (CT=26.5-27.0) and moderately expressed in adult liver (CT=28.5-28.8) and liver cancer cell line HepG2 (CT=28.4-28.8). This result agrees with the results seen in Panel 5 (expression in HepG2 (CT=29.2). These results are in agreement with published data that show a novel sodium dicarboxylate transporter in brain, choroid plexus kidney, intestine and liver. Thus, expression of this gene could be used to differentiate between these samples and other samples on this panel and as a marker for liver derived tissue.


[1290] This gene is expressed at low levels throughout the CNS, including in amygdala, substantia nigra, thalamus, cerebellum, and cerebral cortex. Therefore, this gene may play a role in central nervous system disorders such as Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[1291] Low but significant levels of expression are also seen in the adrenal gland. Thus, this gene product may also be involved in metabolic disorders of this gland, including adrenoleukodystrophy and congenital adrenal hyperplasia.



REFERENCES

[1292] 1. Pajor A M, Gangula R, Yao X. Cloning and functional characterization of a high-affinity Na(+)/dicarboxylate cotransporter from mouse brain. Am J Physiol Cell Physiol May 2001;280(5):C1215-23.


[1293] 2. Chen X Z, Shayakul C, Berger UV, Tian W, Hediger M A. Characterization of a rat Na+-dicarboxylate cotransporter. J Biol Chem Aug. 14, 1998;273(33):20972-81.


[1294] Panel 4.1D Summary: Ag3692 Significant expression of this gene is seen only in kidney and a liver cirrhosis sample (CTs=34.0). These results confirm that this gene is expressed in liver derived samples. The presence in the kidney is also in agreement with published results. Please see Panel 1.4. This gene product may be involved in maintaining or restoring normal function to the kidney during inflammation.


[1295] Panel 4D Summary: Ag3326 Results from one experiment are not included. The amp plot indicates that there were experimental difficulties with this run.


[1296] Panel 5 Islet Summary: Ag3326—The highest expression of this gene is in liver cancer cell line HepG2 (CT=29.2). There is also moderate expression in the small intestine (CT=30.5). These results compare well with previously published reports of sodium dicarboxylate transporter expression in mouse and rat (see discussion Panel 1.4).


[1297] R. CG57758-04 and CG57758-05: Sodium:Sulfate Symporter


[1298] Expression of gene CG57758-04 and CG57758-05, both splice variants of CG577584-01, was assessed using the primer-probe sets Ag3326, Ag3692 and Ag5818, described in Tables RA, RB and RC. Results of the RTQ-PCR runs are shown in Tables RD, RE, RF, RG and RH.


[1299] Table RA. Probe Name Ag3326
737TABLE RAProbe Name Ag3326StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-ccatttactggtgcacagaagt-3′22138438ProbeTET-5′-atccctctggctgtcacctctctcat-3′-TAMRA26161439Reverse5′-ggagtccagaatctggaagagt-3′22205440


[1300] Table RB. Probe Name Ag3692
738TABLE RBProbe Name Ag3692StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-ccatttactggtgcacagaagt-3′22138441ProbeTET-5′-atccctctggctgtcacctctctcat-3′-TAMRA26161442Reverse5′-ggagtccagaatctggaagagt-3′22205443


[1301] Table RC. Probe Name Ag5818
739TABLE RCProbe Name Ag5818StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-ccatcaccttgatcttgtcc-3′201341444ProbeTET-5′-ttatgactcctgttttcaccatggaggca-3′-TAMRA291429445Reverse5′-cagaagactccaattatgttca-3′221458446


[1302]

740





TABLE RD










CNS_neurodegeneration_v1.0















Rel.
Rel.
Rel.

Rel.
Rel.
Rel.



Exp. (%)
Exp. (%)
Exp. (%)

Exp. (%)
Exp. (%)
Exp. (%)



Ag3326,
Ag3692,
Ag3692,

Ag3326,
Ag3692,
Ag3692,


Tissue
Run
Run
Run
Tissue
Run
Run
Run


Name
210144197
211145262
224337942
Name
210144197
211145262
224337942

















AD 1
2.1
4.3
1.0
Control
8.5
15.3
12.0


Hippo



(Path) 3






Temporal






Ctx


AD 2
20.9
28.3
25.0
Control
31.2
36.6
52.1


Hippo



(Path) 4






Temporal






Ctx


AD 3
0.0
0.9
0.6
AD 1
2.7
3.0
0.0


Hippo



Occipital






Ctx


AD 4
2.1
7.1
2.6
AD 2
0.0
0.0
0.0


Hippo



Occipital






Ctx






(Missing)


AD 5
72.7
97.9
85.3
AD 3
1.5
7.2
1.3


hippo



Occipital






Ctx


AD 6
13.7
18.3
5.5
AD 4
71.7
35.6
30.6


Hippo



Occipital






Ctx


Control 2
14.5
20.2
15.2
AD 5
25.3
31.9
12.4


Hippo



Occipital






Ctx


Control 4
11.7
7.4
5.1
AD 6
17.2
19.1
11.2


Hippo



Occipital






Ctx


Control
6.7
4.4
4.5
Control 1
7.0
9.0
8.1


(Path) 3



Occipital


Hippo



Ctx


AD 1
4.0
1.7
2.8
Control 2
33.2
44.8
26.1


Temporal



Occipital


Ctx



Ctx


AD 2
80.7
50.7
37.4
Control 3
30.1
37.6
21.9


Temporal



Occipital


Ctx



Ctx


AD 3
3.6
0.0
1.1
Control 4
16.3
12.6
8.2


Temporal



Occipital


Ctx



Ctx


AD 4
19.5
30.6
15.2
Control
42.0
55.9
52.9


Temporal



(Path) 1


Ctx



Occipital






Ctx


AD 5 Inf
100.0
100.0
99.3
Control
6.7
13.0
7.7


Temporal



(Path) 2


Ctx



Occipital






Ctx


AD 5
32.8
29.1
33.2
Control
8.7
6.6
5.4


SupTemporal



(Path) 3


Ctx



Occipital






Ctx


AD 6 Inf
27.7
21.3
26.6
Control
8.1
9.0
7.4


Temporal



(Path) 4


Ctx



Occipital






Ctx


AD 6 Sup
41.8
53.6
17.0
Control 1
21.2
23.0
15.3


Temporal



Parietal


Ctx



Ctx


Control 1
12.0
33.9
18.3
Control 2
48.6
38.2
22.1


Temporal



Parietal


Ctx



Ctx


Control 2
30.1
49.3
44.4
Control 3
28.3
34.4
32.8


Temporal



Parietal


Ctx



Ctx


Control 3
38.7
39.5
33.4
Control
78.5
97.3
100.0


Temporal



(Path) 1


Ctx



Parietal






Ctx


Control 4
17.6
25.2
24.1
Control
50.7
50.7
37.9


Temporal



(Path) 2


Ctx



Parietal






Ctx


Control
69.7
70.7
49.7
Control
10.7
10.1
9.6


(Path) 1



(Path) 3


Temporal



Parietal


Ctx



Ctx


Control
35.4
50.7
33.4
Control
30.6
24.5
40.9


(Path) 2



(Path) 4


Temporal



Parietal


Ctx



Ctx










[1303]

741





TABLE RE










General_screening_panel_v1.4













Rel. Exp. (%)
Rel. Exp. (%)

Rel. Exp. (%)
Rel. Exp. (%)



Ag3326, Run
Ag3692, Run

Ag3326, Run
Ag3692, Run


Tissue Name
215678613
217131191
Tissue Name
215678613
217131191















Adipose
0.0
0.0
Renal ca. TK-10
11.4
12.0


Melanoma*
0.0
0.0
Bladder
0.0
0.1


Hs688(A).T


Melanoma*
0.1
0.0
Gastric ca. (liver
0.0
0.0


Hs688(B).T


met.) NCI-N87


Melanoma*
0.0
0.0
Gastric ca.
0.0
0.0


M14


KATO III


Melanoma*
0.0
0.0
Colon ca. SW-
0.0
0.0


LOXIMVI


948


Melanoma*
0.0
0.0
Colon ca.
0.0
0.0


SK-MEL-5


SW480


Squamous
0.9
0.7
Colon ca.*
0.0
0.0


cell


(SW480 met)


carcinoma


SW620


SCC-4


Testis Pool
0.1
0.2
Colon ca. HT29
0.0
0.0


Prostate ca.*
0.0
0.0
Colon ca. HCT-
0.0
0.0


(bone met)


116


PC-3


Prostate Pool
0.0
0.0
Colon ca. CaCo-2
0.0
0.0


Placenta
0.0
0.0
Colon cancer
0.1
0.0





tissue


Uterus Pool
0.0
0.0
Colon ca.
0.0
0.0





SW1116


Ovarian ca.
0.0
0.0
Colon ca. Colo-
0.0
0.0


OVCAR-3


205


Ovarian ca.
0.0
0.0
Colon ca. SW-48
0.0
0.0


SK-OV-3


Ovarian ca.
0.1
0.0
Colon Pool
0.6
0.0


OVCAR-4


Ovarian ca.
0.0
0.0
Small Intestine
0.1
0.0


OVCAR-5


Pool


Ovarian ca.
0.0
0.0
Stomach Pool
0.0
0.0


IGROV-1


Ovarian ca.
2.8
2.2
Bone Marrow
0.0
0.1


OVCAR-8


Pool


Ovary
0.7
0.6
Fetal Heart
0.0
0.0


Breast ca.
0.0
0.0
Heart Pool
0.0
0.0


MCF-7


Breast ca.
0.0
0.0
Lymph Node
0.1
0.0


MDA-MB-


Pool


231


Breast ca. BT
0.6
0.8
Fetal Skeletal
0.0
0.0


549


Muscle


Breast ca.
0.0
0.0
Skeletal Muscle
0.0
0.0


T47D


Pool


Breast ca.
0.0
0.0
Spleen Pool
0.4
0.2


MDA-N


Breast Pool
0.0
0.1
Thymus pool
0.0
0.0


Trachea
0.2
0.1
CNS cancer
0.0
0.0





(glio/astro) U87-





MG


Lung
0.0
0.0
CNS cancer
0.0
0.0





(glio/astro) U-





118-MG


Fetal Lung
0.2
0.1
CNS cancer
0.0
0.0





(neuro; met) SK-





N-AS


Lung ca.
0.0
0.0
CNS cancer
0.0
0.0


NCI-N417


(astro) SF-539


Lung ca. LX-1
0.0
0.0
CNS cancer
0.0
0.0





(astro) SNB-75


Lung ca.
0.0
0.0
CNS cancer
0.0
0.0


NCI-H146


(glio) SNB-19


Lung ca.
0.0
0.0
CNS cancer
0.1
0.1


SHP-77


(glio) SF-295


Lung ca.
0.0
0.1
Brain
0.4
0.4


A549


(Amygdala) Pool


Lung ca.
2.0
0.0
Brain
1.4
1.0


NCI-H526


(cerebellum)


Lung ca.
0.7
0.6
Brain (fetal)
0.7
0.4


NCI-H23


Lung ca.
0.0
0.0
Brain
0.5
0.7


NCI-H460


(Hippocampus)





Pool


Lung ca.
0.1
0.2
Cerebral Cortex
1.4
1.5


HOP-62


Pool


Lung ca.
0.0
0.0
Brain (Substantia
1.4
1.4


NCI-H522


nigra) Pool


Liver
28.7
24.1
Brain
1.1
0.9





(Thalamus) Pool


Fetal Liver
100.0
100.0
Brain (whole)
4.1
3.7


Liver ca.
29.5
26.2
Spinal Cord Pool
0.1
0.2


HepG2


Kidney Pool
0.0
0.0
Adrenal Gland
2.6
1.9


Fetal Kidney
0.1
0.1
Pituitary gland
0.0
0.2





Pool


Renal ca.
0.0
0.0
Salivary Gland
40.9
35.1


786-0


Renal ca.
0.0
0.0
Thyroid (female)
0.0
0.0


A498


Renal ca.
0.0
0.0
Pancreatic ca.
0.5
0.8


ACHN


CAPAN2


Renal ca.
0.0
0.0
Pancreas Pool
0.0
0.0


UO-31










[1304]

742





TABLE RF










General_screening_panel_v1.5











Rel. Exp. (%)

Rel. Exp. (%)



Ag5818, Run

Ag5818, Run


Tissue Name
245382899
Tissue Name
245382899













Adipose
0.0
Renal ca. TK-10
13.4


Melanoma*
0.0
Bladder
0.0


Hs688(A).T


Melanoma*
0.0
Gastric ca. (liver met.)
0.0


Hs688(B).T

NCI-N87


Melanoma* M14
0.0
Gastric ca. KATO III
0.0


Melanoma*
0.0
Colon ca. SW-948
0.0


LOXIMVI


Melanoma* SK-
0.0
Colon ca. SW480
0.0


MEL-5


Squamous cell
1.4
Colon ca.* (SW480
0.0


carcinoma SCC-4

met) SW620


Testis Pool
0.5
Colon ca. HT29
0.0


Prostate ca.* (bone
0.0
Colon ca. HCT-116
0.0


met) PC-3


Prostate Pool
0.0
Colon ca. CaCo-2
0.4


Placenta
0.0
Colon cancer tissue
0.0


Uterus Pool
0.0
Colon ca. SW1116
0.0


Ovarian ca.
0.0
Colon ca. Colo-205
0.0


OVCAR-3


Ovarian ca. SK-
0.1
Colon ca. SW-48
0.0


OV-3


Ovarian ca.
0.0
Colon Pool
0.0


OVCAR-4


Ovarian ca.
0.0
Small Intestine Pool
0.0


OVCAR-5


Ovarian ca.
0.0
Stomach Pool
0.0


IGROV-1


Ovarian ca.
1.9
Bone Marrow Pool
0.0


OVCAR-8


Ovary
0.3
Fetal Heart
0.0


Breast ca. MCF-7
0.0
Heart Pool
0.0


Breast ca. MDA-
0.0
Lymph Node Pool
0.0


MB-231


Breast ca. BT 549
0.4
Fetal Skeletal Muscle
0.0


Breast ca. T47D
0.0
Skeletal Muscle Pool
0.0


Breast ca. MDA-N
0.0
Spleen Pool
0.7


Breast Pool
0.0
Thymus Pool
0.0


Trachea
0.2
CNS cancer
0.0




(glio/astro) U87-MG


Lung
0.0
CNS cancer
0.0




(glio/astro) U-118-MG


Fetal Lung
0.2
CNS cancer
0.0




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.0
CNS cancer (astro) SF-
0.0




539


Lung ca. LX-1
0.0
CNS cancer (astro)
0.0




SNB-75


Lung ca. NCI-H146
0.0
CNS cancer (glio)
0.0




SNB-19


Lung ca. SHP-77
0.0
CNS cancer (glio) SF-
0.0




295


Lung ca. A549
0.2
Brain (Amygdala) Pool
0.7


Lung ca. NCI-H526
0.0
Brain (cerebellum)
1.1


Lung ca. NCI-H23
1.5
Brain (fetal)
0.8


Lung ca. NCI-H460
0.0
Brain (Hippocampus)
0.6




Pool


Lung ca. HOP-62
0.0
Cerebral Cortex Pool
1.7


Lung ca. NCI-H522
0.0
Brain (Substantia
1.2




nigra) Pool


Liver
40.3
Brain (Thalamus) Pool
1.3


Fetal Liver
100.0
Brain (whole)
5.6


Liver ca. HepG2
33.2
Spinal Cord Pool
0.3


Kidney Pool
0.0
Adrenal Gland
6.0


Fetal Kidney
0.0
Pituitary gland Pool
0.2


Renal ca. 786-0
0.0
Salivary Gland
67.4


Renal ca. A498
0.0
Thyroid (female)
0.0


Renal ca. ACHN
0.0
Pancreatic ca.
0.7




CAPAN2


Renal ca. UO-31
0.0
Pancreas Pool
0.0










[1305]

743





TABLE RG










Panel 4.1D













Rel.
Rel.

Rel.
Rel.



Exp. (%)
Exp. (%)

Exp. (%)
Exp. (%)



Ag3692,
Ag5818,

Ag3692,
Ag5818,



Run
Run

Run
Run


Tissue Name
169987356
246920287
Tissue Name
169987356
246920287















Secondary Th1 act
0.0
0.0
HUVEC IL-1beta
0.0
0.0


Secondary Th2 act
0.0
0.0
HUVEC IFN
0.0
0.0





gamma


Secondary Tr1 act
0.0
0.0
HUVEC TNF
0.0
0.0





alpha + IFN





gamma


Secondary Th1 rest
0.0
0.0
HUVEC TNF
0.0
0.0





alpha + IL4


Secondary Th2 rest
0.0
0.0
HUVEC IL-11
0.0
0.0


Secondary Tr1 rest
0.0
0.0
Lung
0.0
0.0





Microvascular EC





none


Primary Th1 act
0.0
0.0
Lung
0.0
0.0





Microvascular EC





TNF alpha + IL-





1beta


Primary Th2 act
0.0
0.0
Microvascular
11.3
0.0





Dermal EC none


Primary Tr1 act
4.2
0.0
Microsvasular
0.0
0.0





Dermal EC





TNF alpha + IL-





1beta


Primary Th1 rest
0.0
0.0
Bronchial
28.5
0.0





epithelium





TNF alpha +





IL1beta


Primary Th2 rest
0.0
0.0
Small airway
5.7
0.0





epithelium none


Primary Tr1 rest
0.0
0.0
Small airway
0.0
0.0





epithelium





TNF alpha + IL-





1beta


CD45RA CD4
3.9
0.0
Coronery artery
0.0
0.0


lymphocyte act


SMC rest


CD45RO CD4
0.0
0.0
Coronery artery
0.0
0.0


lymphocyte act


SMC TNF alpha +





IL-1beta


CD8 lymphocyte
0.0
0.0
Astrocytes rest
0.0
0.0


act


Secondary CD8
0.0
0.0
Astrocytes
0.0
0.0


lymphocyte rest


TNF alpha + IL-





1beta


Secondary CD8
0.0
0.0
KU-812
3.6
24.3


lymphocyte act


(Basophil) rest


CD4 lymphocyte
0.0
0.0
KU-812
4.3
0.0


none


(Basophil)





PMA/ionomycin


2ry
0.0
0.0
CCD1106
10.7
0.0


Th1/Th2/Tr1_anti-


(Keratinocytes)


CD95 CH11


none


LAK cells rest
0.0
0.0
CCD1106
0.0
0.0





(Keratinocytes)





TNF alpha + IL-





1beta


LAK cells IL-2
0.0
0.0
Liver cirrhosis
94.0
27.5


LAK cells IL-
0.0
0.0
NCI-H292 none
0.0
0.0


2 + IL-12


LAK cells IL-
0.0
0.0
NCI-H292 IL-4
0.0
0.0


2 + IFN gamma


LAK cells IL-2 +
0.0
0.0
NCI-H292 IL-9
0.0
0.0


IL-18


LAK cells
0.0
0.0
NCI-H292 IL-13
0.0
0.0


PMA/ionomycin


NK Cells IL-2 rest
0.0
0.0
NCI-H292 IFN
0.0
0.0





gamma


Two Way MLR 3
0.0
0.0
HPAEC none
0.0
0.0


day


Two Way MLR 5
3.2
0.0
HPAEC TNF
0.0
0.0


day


alpha + IL-1beta


Two Way MLR 7
0.0
0.0
Lung fibroblast
0.0
0.0


day


none


PBMC rest
0.0
0.0
Lung fibroblast
0.0
0.0





TNF alpha + IL-





1beta


PBMC PWM
0.0
0.0
Lung fibroblast
0.0
0.0





IL-4


PBMC PHA-L
0.0
0.0
Lung fibroblast
0.0
0.0





IL-9


Ramos (B cell)
0.0
0.0
Lung fibroblast
0.0
0.0


none


IL-13


Ramos (B cell)
0.0
0.0
Lung fibroblast
0.0
0.0


ionomycin


IFN gamma


B lymphocytes
0.0
0.0
Dermal fibroblast
0.0
0.0


PWM


CCD1070 rest


B lymphocytes
0.0
0.0
Dermal fibroblast
0.0
0.0


CD40L and IL-4


CCD1070 TNF





alpha


EOL-1 dbcAMP
0.0
0.0
Dermal fibroblast
0.0
0.0





CCD1070 IL-





1beta


EOL-1 dbcAMP
0.0
0.0
Dermal fibroblast
0.0
0.0


PMA/ionomycin


IFN gamma


Dendritic cells
0.0
0.0
Dermal fibroblast
0.0
0.0


none


IL-4


Dendritic cells LPS
0.0
0.0
Dermal
0.0
0.0





Fibroblasts rest


Dendritic cells
0.0
0.0
Neutrophils
0.0
0.0


anti-CD40


TNFa + LPS


Monocytes rest
0.0
0.0
Neutrophils rest
0.0
0.0


Monocytes LPS
0.0
0.0
Colon
0.0
0.0


Macrophages rest
0.0
0.0
Lung
0.0
0.0


Macrophages LPS
0.0
0.0
Thymus
2.4
0.0


HUVEC none
0.0
0.0
Kidney
100.0
100.0


HUVEC starved
0.0
0.0










[1306]

744





TABLE RH










Panel 5 Islet











Rel. Exp. (%)

Rel. Exp. (%)



Ag3326, Run

Ag3326, Run


Tissue Name
242385365
Tissue Name
242385365













97457_Patient-
0.0
94709_Donor 2 AM - A_adipose
0.2


02go_adipose


97476_Patient-
0.0
94710_Donor 2 AM - B_adipose
0.0


07sk_skeletal muscle


97477_Patient-
0.0
94711_Donor 2 AM - C_adipose
0.0


07ut_uterus


97478_Patient-
0.0
94712_Donor 2 AD - A_adipose
0.0


07pl_placenta


99167_Bayer Patient
0.3
94713_Donor 2 AD - B_adipose
0.0


1


97482_Patient-
0.0
94714_Donor 2 AD - C_adipose
0.0


08ut_uterus


97483_Patient-
0.0
94742_Donor 3 U -
0.0


08pl_placenta

A_Mesenchymal Stem Cells


97486_Patient-
0.0
94743_Donor 3 U -
0.0


09sk_skeletal muscle

B_Mesenchymal Stem Cells


97487_Patient-
0.0
94730_Donor 3 AM - A_adipose
0.0


09ut_uterus


97488_Patient-
0.0
94731_Donor 3 AM - B_adipose
0.0


09pl_placenta


97492_Patient-
0.0
94732_Donor 3 AM - C_adipose
0.0


10ut_uterus


97493_Patient-
0.0
94733_Donor 3 AD - A_adipose
0.0


10pl_placenta


97495_Patient-
0.0
94734_Donor 3 AD - B_adipose
0.0


11go_adipose


97496_Patient-
0.0
94735_Donor 3 AD - C_adipose
0.0


11sk_skeletal muscle


97497_Patient-
0.0
77138_Liver_HepG2untreated
100.0


11ut_uterus


97498_Patient-
0.0
73556_Heart_Cardiac stromal
0.0


11pl_placenta

cells (primary)


97500_Patient-
0.1
81735_Small Intestine
39.5


12go_adipose


97501_Patient-
0.3
72409_Kidney_Proximal
0.0


12sk_skeletal muscle

Convoluted Tubule


97502_Patient-
0.0
82685_Small
0.0


12ut_uterus

intestine_Duodenum


97503_Patient-
0.0
90650_Adrenal_Adrenocortical
0.0


12pl_placenta

adenoma


94721_Donor 2 U -
0.0
72410_Kidney_HRCE
0.0


A_Mesenchymal


Stem Cells


94722_Donor 2 U -
0.0
72411_Kidney_HRE
0.0


B_Mesenchymal


Stem Cells


94723_Donor 2 U -
0.0
73139_Uterus_Uterine smooth
0.0


C_Mesenchymal

muscle cells


Stem Cells










[1307] CNS_neurodegeneration_v1.0 Summary: Ag3326/Ag3692—Three experiments done with two primer pairs (same sequence) are in excellent agreement. This panel confirms the expression of this gene at low levels in the brain in an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of the potential utility of this gene in treatment of central nervous system disorders. Ag5818 Results from one experiment are not included. The amp plot indicates that there were experimental difficulties with this run.


[1308] General_screening_panel_v1.4 Summary: Ag3326/Ag3692 Two experiments with the same probe and primer set produce results that are in excellent agreement. This gene is highly expressed in fetal liver (CT=26.5-27.0) and moderately expressed in adult liver (CT=28.5-28.8) and liver cancer cell line HepG2 (CT=28.4-28.8). This result agrees with In the results seen in Panel 5 (expression in HepG2 (CT=29.2). These results are in agreement with published data that show a novel sodium dicarboxylate transporter in brain, choroid plexus kidney, intestine and liver. Thus, expression of this gene could be used to differentiate between these samples and other samples on this panel and as a marker for liver derived tissue.


[1309] This gene is expressed at low levels throughout the CNS, including in amygdala, substantia nigra, thalamus, cerebellum, and cerebral cortex. Therefore, this gene may play a role in central nervous system disorders such as Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[1310] Low but significant levels of expression are also seen in the adrenal gland. Thus, this gene product may also be involved in metabolic disorders of this gland, including adrenoleukodystrophy and congenital adrenal hyperplasia.



REFERENCES

[1311] 1. Pajor A M, Gangula R, Yao X. Cloning and functional characterization of a high-affinity Na(+)/dicarboxylate cotransporter from mouse brain. Am J Physiol Cell Physiol May 2001;280(5):C1215-23.


[1312] 2. Chen X Z, Shayakul C, Berger UV, Tian W, Hediger M A. Characterization of a rat Na+-dicarboxylate cotransporter. J Biol Chem Aug. 14, 1998;273(33):20972-81.


[1313] General_screening_panel_v1.5 Summary: Ag5818 Results using this primer pair are in excellent agreement with the results seen in panel 1.4. See Panel 1.4 for discussion. Panel 4.1D Summary: Ag3692 Significant expression of this gene is seen only in kidney and a liver cirrhosis sample (CTs=34.0). These results confirm that this gene is expressed in liver derived samples. The presence in the kidney is also in agreement with published results. Please see Panel 1.4. This gene product may be involved in maintaining or restoring normal function to the kidney during inflammation.


[1314] Panel 4D Summary: Ag3326 Results from one experiment are not included. The amp plot indicates that there were experimental difficulties with this run.


[1315] Panel 5 Islet Summary: Ag3326 The highest expression of this gene is in liver cancer cell line HepG2 (CT=29.2). There is also moderate expression in the small intestine (CT=30.5). These results compare well with previously published reports of sodium dicarboxylate transporter expression in mouse and rat (see discussion Panel 1.4).


[1316] S. CG57732-01 and CG57732-02 and CG57732-03: CA2+/Calmodulin-Dependent Protein Kinase IV Kinase


[1317] Expression of gene CG57732-01 and full length clones CG57732-02 and CG57732-03, was assessed using the primer-probe set Ag3317, described in Table SA. Results of the RTQ-PCR runs are shown in Tables SB, SC and SD. Please note CG57732-03 represents a splice variant of CG57732-01.


[1318] Table SA. Probe Name Ag3317
745TABLE SAProbe Name Ag3317StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-ggcctacaacgaaagtgaaga-3′21451447ProbeTET-5′-cagacactatgcaatgaaagtcctttcca-3′-TAMRA29472448Reverse5′-ggaaagccatactgcttcagta-3′22510449


[1319]

746





TABLE SB










CNS_neurodegeneration_v1.0













Rel. Exp.



Rel. Exp. (%)

(%) Ag3317,



Ag3317, Run

Run


Tissue Name
210144081
Tissue Name
210144081













AD 1 Hippo
10.7
Control (Path) 3
4.1




Temporal Ctx


AD 2 Hippo
23.7
Control (Path) 4
42.6




Temporal Ctx


AD 3 Hippo
4.5
AD 1 Occipital
12.5




Ctx


AD 4 Hippo
7.5
AD 2 Occipital
0.0




Ctx (Missing)


AD 5 hippo
97.9
AD 3 Occipital
5.4




Ctx


AD 6 Hippo
25.7
AD 4 Occipital
18.4




Ctx


Control 2 Hippo
24.8
AD 5 Occipital
21.8




Ctx


Control 4 Hippo
4.3
AD 6 Occipital
58.6




Ctx


Control (Path) 3
2.8
Control 1 Occipital
1.5


Hippo

Ctx


AD 1 Temporal Ctx
10.4
Control 2 Occipital
94.0




Ctx


AD 2 Temporal Ctx
35.8
Control 3 Occipital
21.5




Ctx


AD 3 Temporal Ctx
5.8
Control 4 Occipital
2.6




Ctx


AD 4 Temporal Ctx
23.2
Control (Path) 1
100.0




Occipital Ctx


AD 5 Inf Temporal
88.9
Control (Path) 2
13.8


Ctx

Occipital Ctx


AD 5 Sup Temporal
26.6
Control (Path) 3
0.9


Ctx

Occipital Ctx


AD 6 Inf Temporal
39.5
Control (Path) 4
19.6


Ctx

Occipital Ctx


AD 6 Sup Temporal
47.3
Control 1 Parietal
4.9


Ctx

Ctx


Control 1 Temporal
4.4
Control 2 Parietal
33.0


Ctx

Ctx


Control 2 Temporal
63.3
Control 3 Parietal
27.4


Ctx

Ctx


Control 3 Temporal
20.4
Control (Path) 1
95.9


Ctx

Parietal Ctx


Control 4 Temporal
8.7
Control (Path) 2
24.5


Ctx

Parietal Ctx


Control (Path) 1
77.4
Control (Path) 3
2.0


Temporal Ctx

Parietal Ctx


Control (Path) 2
38.7
Control (Path) 4
51.8


Temporal Ctx

Parietal Ctx










[1320]

747





TABLE SC










General_screening_panel_v1.4











Rel. Exp.

Rel. Exp.



(%) Ag3317,

(%) Ag3317,



Run

Run


Tissue Name
215678602
Tissue Name
215678602













Adipose
2.4
Renal ca. TK-10
14.2


Melanoma*
6.2
Bladder
10.5


Hs688(A).T


Melanoma*
7.9
Gastric ca. (liver met)
22.2


Hs688(B).T

NCI-N87


Melanoma* M14
18.2
Gastric ca. KATO
23.0




III


Melanoma*
9.4
Colon ca. SW-948
11.1


LOXIMVI


Melanoma* SK-
9.8
Colon ca. SW480
20.9


MEL-5


Squamous cell
1.6
Colon ca.* (SW
21.6


carcinoma SCC-4

480 met) SW620


Testis Pool
13.1
Colon ca. HT29
11.3


Prostate ca.* (bone
6.4
Colon ca. HCT-116
27.0


met) PC-3


Prostate Pool
3.1
Colon ca. CaCo-2
1.6


Placenta
1.8
Colon cancer tissue
11.3


Uterus Pool
3.9
Colon ca. SW1116
9.7


Ovarian ca.
11.6
Colon ca. Colo-205
1.7


OVCAR-3


Ovarian ca. SK-
18.7
Colon ca. SW-48
8.8


OV-3


Ovarian ca.
3.4
Colon Pool
17.1


OVCAR-4


Ovarian ca.
17.2
Small Intestine Pool
21.2


OVCAR-5


Ovarian ca.
6.2
Stomach Pool
5.3


IGROV-1


Ovarian ca.
4.7
Bone Marrow Pool
5.1


OVCAR-8


Ovary
2.9
Fetal Heart
6.8


Breast ca. MCF-7
6.1
Heart Pool
5.4


Breast ca. MDA-
20.3
Lymph Node Pool
13.4


MB-231


Breast ca. BT 549
7.4
Fetal Skeletal Muscle
2.6


Breast ca. T47D
37.9
Skeletal Muscle Pool
2.3


Breast ca. MDA-N
9.0
Spleen Pool
2.8


Breast Pool
12.0
Thymus Pool
9.0


Trachea
17.2
CNS cancer
66.4




(glio/astro) U87-MG


Lung
0.7
CNS cancer
53.2




(glio/astro) U-118-MG


Fetal Lung
6.0
CNS cancer
4.6




(neuro; met) SK-N-AS


Lung ca. NCI-N417
16.5
CNS cancer (astro)
17.2




SF-539


Lung ca. LX-1
20.9
CNS cancer (astro)
21.5




SNB-75


Lung ca. NCI-H146
7.0
CNS cancer (glio)
5.1




SNB-19


Lung ca. SHP-77
23.0
CNS cancer (glio)
12.2




SF-295


Lung ca. A549
23.7
Brain (Amygdala)
46.3




Pool


Lung ca. NCI-H526
4.4
Brain (Cerebellum)
92.7


Lung ca. NCI-H23
5.8
Brain (fetal)
25.7


Lung ca. NCI-H460
10.3
Brain (Hippocampus)
42.9




Pool


Lung ca. HOP-62
7.0
Cerebral Cortex Pool
100.0


Lung ca. NCI-H522
2.9
Brain (Substantia
76.3




nigra) Pool


Liver
0.1
Brain (Thalamus) Pool
63.7


Fetal Liver
1.3
Brain (whole)
56.6


Liver ca. HepG2
1.4
Spinal Cord Pool
9.3


Kidney Pool
26.2
Adrenal Gland
16.2


Fetal Kidney
3.5
Pituitary gland Pool
16.4


Renal ca. 786-0
26.4
Salivary Gland
13.4


Renal ca. A498
14.2
Thyroid (female)
6.3


Renal ca. ACHN
33.2
Pancreatic ca.
2.6




CAPAN2


Renal ca. UO-31
4.3
Pancreas Pool
19.6










[1321]

748





TABLE SD










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3317, Run

Ag3317, Run


Tissue Name
164683049
Tissue Name
164683049













Secondary Th1 act
21.6
HUVEC IL-1beta
3.8


Secondary Th2 act
23.2
HUVEC IFN gamma
12.5


Secondary Tr1 act
22.8
HUVEC TNF alpha +
2.9




IFN gamma


Secondary Th1 rest
12.7
HUVEC TNF alpha +
9.0




IL4


Secondary Th2 rest
9.3
HUVEC IL-11
4.0


Secondary Tr1 rest
33.7
Lung Microvascular EC
24.3




none


Primary Th1 act
44.1
Lung Microvascular EC
11.3




TNF alpha + IL-1beta


Primary Th2 act
49.3
Microvascular Dermal
41.5




none


Primary Tr1 act
74.2
Microsvasular Dermal EC
17.2




TNF alpha + IL-1beta


Primary Th1 rest
38.2
Bronchial epithelium
31.2




TNF alpha + IL1beta


Primary Th2 rest
44.4
Small airway epithelium
8.0




none


Primary Tr1 rest
50.0
Small airway epithelium
11.1




TNF alpha + IL-1beta


CD45RA CD4
41.2
Coronery artery SMC rest
20.6


lymphocyte act


CD45RO CD4
25.0
Coronery artery SMC
19.6


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
17.8
Astrocytes rest
14.7


Secondary CD8
21.8
Astrocytes TNF alpha +
11.0


lymphocyte rest

IL-1beta


Secondary CD8
7.4
KU-812 (Basophil) rest
2.1


lymphocyte act


CD4 lymphocyte none
21.8
KU-812 (Basophil)
12.9




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
5.8
CCD1106
30.6


CD95 CH11

(Keratinocytes) none


LAK cells rest
51.1
CCD1106
23.7




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
7.0
Liver cirrhosis
0.8


LAK cells IL-2 + IL-12
25.5
Lupus kidney
2.2


LAK cells IL-2 + IFN
35.4
NCI-H292 none
33.7


gamma


LAK cells IL-2 + IL-18
28.7
NCI-H292 IL-4
43.5


LAK cells
20.6
NCI-H292 IL-9
36.3


PMA/ionomycin


NK Cells IL-2 rest
13.5
NCI-H292 IL-13
35.6


Two Way MLR 3 day
33.0
NCI-H292 IFN gamma
24.3


Two Way MLR 5 day
9.6
HPAEC none
22.8


Two Way MLR 7 day
10.0
HPAEC TNF alpha + IL-
8.3




1beta


PBMC rest
12.0
Lung fibroblast none
11.8


PBMC PWM
24.7
Lung fibroblast TNF
1.2




alpha + IL-1beta


PBMC PHA-L
32.5
Lung fibroblast IL-4
19.2


Ramos (B cell) none
1.5
Lung fibroblast IL-9
12.1


Ramos (B cell)
0.0
Lung fibroblast IL-13
14.8


ionomycin


B lymphocytes PWM
41.2
Lung fibroblast IFN
17.2




gamma


B lymphocytes CD40L
14.5
Dermal fibroblast
100.0


and IL-4

CCD1070 rest


EOL-1 dbcAMP
20.0
Dermal fibroblast
57.8




CCD1070 TNF alpha


EOL-1 dbcAMP
60.3
Dermal fibroblast
14.2


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
55.5
Dermal fibroblast IFN
24.1




gamma


Dendritic cells LPS
26.1
Dermal fibroblast IL-4
39.0


Dendritic cells anti-
74.7
IBD Colitis 2
1.6


CD40


Monocytes rest
48.0
IBD Crohn's
2.7


Monocytes LPS
15.4
Colon
19.1


Macrophages rest
98.6
Lung
14.4


Macrophages LPS
5.6
Thymus
10.5


HUVEC none
27.9
Kidney
100.0


HUVEC starved
27.0










[1322] CNS_neurodegeneration_v1.0 Summary: Ag3317—This panel does not show differential expression of this gene in Alzheimer's disease. However, this expression profile confirms the presence of this gene in the brain. Please see Panel 1.4 for discussion of utility of this gene in the central nervous system.


[1323] General_screening_panel_v1.4 Summary: Ag3317—There is low to moderate expression this gene across all samples on this panel. This gene is expressed at moderate levels throughout the CNS, including in amygdala, substantia nigra, thalamus, cerebellum, and cerebral cortex. Highest expression is observed in the cerebral cortex (CT=29.0). This gene encodes a calmodulin-dependent protein kinase IV homolog, which is known to play a role in. Ca2+ signaling in the CNS that controls neuronal growth, differentiation, and plasticity. Mice deficient in calmodulin-dependent protein kinase IV were found to have cerebellar defects. Therefore, this gene may play a role in central nervous system disorders such as Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[1324] This gene product is also expressed in adipose, pancreas, adrenal, thyroid, pituitary, skeletal muscle, heart, and liver. This widespread expression in tissues with metabolic function suggests that this gene product may be important for the pathogenesis, diagnosis, and/or treatment of metabolic and endocrine diseases, including obesity and Types 1 and 2 diabetes.


[1325] Based on expression in this panel, this gene may be also be involved in gastric, pancreatic, brain, colon, renal, lung, breast, ovarian and prostate cancer as well as melanomas. Thus, expression of this gene could be used as a diagnostic marker for the presence of these cancers. Furthermore, therapeutic inhibition using antibodies or small molecule drugs might be of use in the treatment of these cancers.



REFERENCES

[1326] 1. Okuno S, Kitani T, Fujisawa H. Evidence for the existence of Ca2+/calmodulin-dependent protein kinase IV kinase isoforms in rat brain. J Biochem (Tokyo) June 1996;119(6):1176-81.


[1327] 2. Ribar T J, Rodriguiz R M, Khiroug L, Wetsel W C, Augustine G J, Means A R. Cerebellar defects in Ca2+/calmodulin kinase IV-deficient mice. J Neurosci Nov. 15, 2000;20(2C2):RC 107.


[1328] Panel 4D Summary: Ag3317—This gene was found to have low expression across almost all the samples on this panel, with the highest level of expression seen in kidney and resting dermal Fibroblasts (CTs=32). Expression of Ca2+/calmodulin-dependent kinase type IV in thymocytes has been found in mice, where it plays a role in Ca2+-dependent gene transcription.


[1329] REFERENCE


[1330] 1. Raman V, Blaeser F, Ho N, Engle D L, Williams C B, Chatila T A. Requirement for Ca2+/calmodulin-dependent kinase type IV/Gr in setting the thymocyte selection threshold. J Immunol Dec. 1, 2001;167(11):6270-8.


[1331] T. CG57709-01: Novel Mitochondrial Protein


[1332] Expression of gene CG57709-01 was assessed using the primer-probe set Ag3323, described in Table TA. Results of the RTQ-PCR runs are shown in Tables TB, TC and TD.


[1333] Table TA. Probe Name Ag3323
749TABLE TAProbe Name Ag3323StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-atgtgcagaggatacgcatg-3′20589450ProbeTET-5′-tgcaaaacaggaagacaaaggaaggg-3′-TAMRA26626451Reverse5′-tggttctggcattctagacg-3′20665452


[1334]

750





TABLE TB










CNS_neurodegeneration_v1.0











Rel. Exp.

Rel. Exp.



(%) Ag3323,

(%) Ag3323,



Run

Run


Tissue Name
210144152
Tissue Name
210144152













AD 1 Hippo
22.5
Control (Path) 3
5.2




Temporal Ctx


AD 2 Hippo
29.5
Control (Path) 4
32.5




Temporal Ctx


AD 3 Hippo
6.9
AD 1 Occipital
18.6




Ctx


AD 4 Hippo
7.4
AD 2 Occipital
0.0




Ctx (Missing)


AD 5 hippo
82.4
AD 3 Occipital
7.6




Ctx


AD 6 Hippo
66.4
AD 4 Occipital
17.8




Ctx


Control 2 Hippo
27.5
AD 5 Occipital
30.8




Ctx


Control 4 Hippo
11.9
AD 6 Occipital
48.6




Ctx


Control (Path) 3
8.4
Control 1 Occipital
4.0


Hippo

Ctx


AD 1 Temporal Ctx
18.6
Control 2 Occipital
58.2




Ctx


AD 2 Temporal Ctx
30.6
Control 3 Occipital
14.2




Ctx


AD 3 Temporal Ctx
7.6
Control 4 Occipital
6.6




Ctx


AD 4 Temporal Ctx
21.5
Control (Path) 1
70.7




Occipital Ctx


AD 5 Inf Temporal
100.0
Control (Path) 2
12.6


Ctx

Occipital Ctx


AD 5 Sup Temporal
42.6
Control (Path) 3
2.4


Ctx

Occipital Ctx


AD 6 Inf Temporal
48.6
Control (Path) 4
14.6


Ctx

Occipital Ctx


AD 6 Sup Temporal
42.0
Control 1 Parietal
6.5


Ctx

Ctx


Control 1 Temporal
6.3
Control 2 Parietal
48.0


Ctx

Ctx


Control 2 Temporal
39.0
Control 3 Parietal
19.6


Ctx

Ctx


Control 3 Temporal
13.1
Control (Path) 1
61.1


Ctx

Parietal Ctx


Control 4 Temporal
8.9
Control (Path) 2
19.3


Ctx

Parietal Ctx


Control (Path) 1
53.6
Control (Path) 3
3.8


Temporal Ctx

Parietal Ctx


Control (Path) 2
34.2
Control (Path) 4
42.6


Temporal Ctx

Parietal Ctx










[1335]

751





TABLE TC










Panel 1.3D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3323,

Ag3323,


Tissue Name
Run 165678151
Tissue Name
Run 165678151













Liver adenocarcinoma
25.0
Kidney (fetal)
6.5


Pancreas
12.8
Renal ca. 786-0
14.3


Pancreatic ca. CAPAN 2
24.5
Renal ca. A498
34.2


Adrenal gland
12.2
Renal ca. RXF 393
14.2


Thyroid
6.9
Renal ca. ACHN
12.9


Salivary gland
14.0
Renal ca. UO-31
48.6


Pituitary gland
10.1
Renal ca. TK-10
7.2


Brain (fetal)
13.7
Liver
20.2


Brain (whole)
29.7
Liver (fetal)
22.1


Brain (amygdala)
21.3
Liver ca.
21.3




(hepatoblast) HepG2


Brain (cerebellum)
24.7
Lung
6.7


Brain (hippocampus)
25.7
Lung (fetal)
14.8


Brain (substantia nigra)
20.0
Lung ca. (small cell)
39.8




LX-1


Brain (thalamus)
27.2
Lung ca. (small cell)
25.0




NCI-H69


Cerebral Cortex
33.0
Lung ca. (s.cell var.)
42.3




SHP-77


Spinal cord
16.5
Lung ca. (large
25.7




cell)NCI-H460


glio/astro U87-MG
8.9
Lung ca. (non-sm.
12.0




cell) A549


glio/astro U-118-MG
100.0
Lung ca. (non-s.cell)
9.1




NCI-H23


astrocytoma SW1783
14.6
Lung ca. (non-s.cell)
9.5




HOP-62


neuro*; met SK-N-AS
43.2
Lung ca. (non-s.cl)
10.7




NCI-H522


astrocytoma SF-539
13.9
Lung ca. (squam.)
12.4




SW 900


astrocytoma SNB-75
29.7
Lung ca. (squam.)
59.0




NCI-H596


glioma SNB-19
13.5
Mammary gland
10.6


glioma U251
43.8
Breast ca.* (pl.ef)
46.3




MCF-7


glioma SF-295
17.7
Breast ca.* (pl.ef)
31.6




MDA-MB-231


Heart (fetal)
22.7
Breast ca.* (pl.ef)
15.1




T47D


Heart
14.5
Breast ca. BT-549
54.0


Skeletal muscle (fetal)
6.8
Breast ca. MDA-N
11.5


Skeletal muscle
55.5
Ovary
8.7


Bone marrow
10.7
Ovarian ca.
26.2




OVCAR-3


Thymus
5.5
Ovarian ca.
21.6




OVCAR-4


Spleen
13.3
Ovarian ca.
20.9




OVCAR-5


Lymph node
24.8
Ovarian ca.
12.6




OVCAR-8


Colorectal
8.8
Ovarian ca. IGROV-1
4.4


Stomach
15.1
Ovarian ca.*
23.5




(ascites) SK-OV-3


Small intestine
28.3
Uterus
14.3


Colon ca. SW480
27.5
Placenta
6.9


Colon ca.*
17.6
Prostate
9.5


SW620(SW480 met)


Colon ca. HT29
14.6
Prostate ca.* (bone
17.7




met)PC-3


Colon ca. HCT-116
43.2
Testis
10.1


Colon ca. CaCo-2
12.7
Melanoma
7.6




Hs688(A).T


Colon ca.
22.5
Melanoma* (met)
6.6


tissue(ODO3866)

Hs688(B).T


Colon ca. HCC-2998
25.2
Melanoma UACC-
19.6




62


Gastric ca.* (liver met)
29.5
Melanoma M14
39.2


NCI-N87


Bladder
6.1
Melanoma LOX
13.4




IMVI


Trachea
13.2
Melanoma* (met)
21.2




SK-MEL-5


Kidney
15.6
Adipose
6.5










[1336]

752





TABLE TD










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3323, Run

Ag3323, Run


Tissue Name
165296416
Tissue Name
165296416













Secondary Th1 act
32.3
HUVEC IL-1beta
3.8


Secondary Th2 act
22.8
HUVEC IFN gamma
12.0


Secondary Tr1 act
29.9
HUVEC TNF alpha +
8.1




IFN gamma


Secondary Th1 rest
3.8
HUVEC TNF alpha +
11.1




IL4


Secondary Th2 rest
4.3
HUVEC IL-11
8.4


Secondary Tr1 rest
6.0
Lung Microvascular EC
7.6




none


Primary Th1 act
33.0
Lung Microvascular EC
6.9




TNF alpha + IL-1beta


Primary Th2 act
25.0
Microvascular Dermal
14.7




EC none


Primary Tr1 act
40.1
Microsvasular Dermal
7.6




EC TNF alpha + IL-1beta


Primary Th1 rest
17.8
Bronchial epithelium
17.3




TNF alpha + IL1beta


Primary Th2 rest
11.6
Small airway epithelium
6.6




none


Primary Tr1 rest
15.0
Small airway epithelium
18.4




TNF alpha + IL-1beta


CD45RA CD4
15.0
Coronery artery SMC rest
9.9


lymphocyte act


CD45RO CD4
24.7
Coronery artery SMC
6.5


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
19.3
Astrocytes rest
5.1


Secondary CD8
22.7
Astrocytes TNF alpha +
3.9


lymphocyte rest

IL-1beta


Secondary CD8
12.9
KU-812 (Basophil) rest
14.0


lymphocyte act


CD4 lymphocyte none
2.9
KU-812 (Basophil)
22.1




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
5.4
CCD1106
16.0


CD95 CH11

(Keratinocytes) none


LAK cells rest
7.2
CCD1106
8.1




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
17.2
Liver cirrhosis
1.7


LAK cells IL-2 + IL-12
15.1
Lupus kidney
1.0


LAK cells IL-2 + IFN
27.9
NCI-H292 none
30.1


gamma


LAK cells IL-2 + IL-18
17.7
NCI-H292 IL-4
49.0


LAK cells
1.9
NCI-H292 IL-9
33.2


PMA/ionomycin


NK Cells IL-2 rest
8.4
NCI-H292 IL-13
26.2


Two Way MLR 3 day
9.9
NCI-H292 IFN gamma
26.6


Two Way MLR 5 day
18.4
HPAEC none
11.7


Two Way MLR 7 day
8.9
HPAEC TNF alpha + IL-
7.5




1beta


PBMC rest
3.8
Lung fibroblast none
8.0


PBMC PWM
50.3
Lung fibroblast TNF
5.5




alpha + IL-1beta


PBMC PHA-L
29.3
Lung fibroblast IL-4
19.1


Ramos (B cell) none
33.9
Lung fibroblast IL-9
15.3


Ramos (B cell)
83.5
Lung fibroblast IL-13
11.4


ionomycin


B lymphocytes PWM
100.0
Lung fibroblast IFN
16.5




gamma


B lymphocytes CD40L
22.4
Dermal fibroblast
28.9


and IL-4

CCD1070 rest


EOL-1 dbcAMP
10.5
Dermal fibroblast
31.2




CCD1070 TNF alpha


EOL-1 dbcAMP
3.7
Dermal fibroblast
11.3


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
9.9
Dermal fibroblast IFN
5.2




gamma


Dendritic cells LPS
6.3
Dermal fibroblast IL-4
12.3


Dendritic cells anti-
7.3
IBD Colitis 2
0.7


CD40


Monocytes rest
7.0
IBD Crohn's
1.0


Monocytes LPS
1.4
Colon
8.8


Macrophages rest
13.5
Lung
5.8


Macrophages LPS
3.5
Thymus
17.3


HUVEC none
11.9
Kidney
12.3


HUVEC starved
24.8










[1337] CNS_neurodegeneration_v1.0 Summary: Ag3323 This panel does not show differential expression of the CG57709-01 gene in Alzheimer's disease. However, this expression profile confirms the presence of this gene in the brain. Please see Panel 1.3D for discussion of utility of this gene in the central nervous system.


[1338] Panel 1.3D Summary: Ag3323—This gene is expressed at moderate levels in all samples on this panel, with highest expression in a brain cancer cell line. Expression is also seen in all the cancer cell lines on this panel. Thus, expression of this gene could be used to differentiate between this brain cancer cell line sample and other samples on this panel and as a marker for brain cancer.


[1339] Among tissues with metabolic function, this gene is expressed at moderate to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.


[1340] This molecule is also expressed at moderate to low levels in the CNS and may be a small molecule target for the treatment of neurologic diseases such as Alzheimer's disease, Parkinson's disease, epilepsy, schizophrenia, stroke and multiple sclerosis.


[1341] Panel 4D Summary: Ag3323—This gene is expressed at high to moderate levels in all samples on this panel, with highest expression in B lymphocytes stimulated with polkweed mitoger (CT=24.5). In addition, this gene is expressed at higher levels in ionomycin-activated Ramos B lymphocytes. The high levels of expression in activated B lymphocytes suggests that therapies that antagonize the function of this gene product may reduce or eliminate the symptoms in patients with autoimmune and inflammatory diseases in which B cells play a part in the initiation or progression of the disease process, such as lupus erythemratosus, Crohn's disease, ulcerative colitis, multiple sclerosis, chronic obstructive pulmonary disease, asthma, emphysema, rheumatoid arthritis, or psoriasis.


[1342] U. CG57700-01: Hydroxyacylglutathione Hydrolase (Glyoxalase II)


[1343] Expression of gene CG57700-01 was assessed using the primer-probe set Ag3311, described in Table UA. Results of the RTQ-PCR runs are shown in Table UB.


[1344] Table UA. Probe Name Ag3311
753TABLE UAProbe Name Ag3311StartPrimersSequencesLengthPositionSEQ ID NO:Forward5′-acgcttagcaacctggagtt-3′20536453ProbeTET-5′-accacgtgagagccaagctgtcct-3′-TAMRA24582454Reverse5′-gtcatcctcatccctcttctg-3′21611456


[1345]

754





TABLE UB










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3311, Run

Ag3311, Run


Tissue Name
164682845
Tissue Name
164682845













Secondary Th1 act
10.2
HUVEC IL-1beta
0.0


Secondary Th2 act
3.8
HUVEC IFN gamma
0.0


Secondary Tr1 act
0.0
HUVEC TNF alpha +
0.0




IFN gamma


Secondary Th1 rest
0.0
HUVEC TNF alpha +
0.0




IL4


Secondary Th2 rest
0.0
HUVEC IL-11
0.0


Secondary Tr1 rest
0.0
Lung Microvascular EC
0.0




none


Primary Th1 act
0.0
Lung Microvascular EC
0.0




TNF alpha + IL-1beta


Primary Th2 act
0.0
Microvascular Dermal
0.0




EC none


Primary Tr1 act
1.6
Microsvasular Dermal
0.0




EC TNF alpha + IL-1beta


Primary Th1 rest
0.0
Bronchial epithelium
5.1




TNF alpha + IL1beta


Primary Th2 rest
0.0
Small airway epithelium
0.0




none


Primary Tr1 rest
0.0
Small airway epithelium
0.0




TNF alpha + IL-1beta


CD45RA CD4
0.0
Coronery artery SMC rest
0.0


lymphocyte act


CD45RO CD4
0.0
Coronery artery SMC
0.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
0.0
Astrocytes rest
0.0


Secondary CD8
0.0
Astrocytes TNF alpha +
0.0


lymphocyte rest

IL-1beta


Secondary CD8
0.0
KU-812 (Basophil) rest
0.0


lymphocyte act


CD4 lymphocyte none
0.0
KU-812 (Basophil)
0.0




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
0.0
CCD1106
4.2


CD95 CH11

(Keratinocytes) none


LAK cells rest
0.0
CCD1106
2.7




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
0.0
Liver cirrhosis
0.0


LAK cells IL-2 + IL-12
0.0
Lupus kidney
0.0


LAK cells IL-2 + IFN
0.0
NCI-H292 none
0.0


gamma


LAK cells IL-2 + IL-18
0.0
NCI-H292 IL-4
0.0


LAK cells
0.0
NCI-H292 IL-9
0.0


PMA/ionomycin


NK Cells IL-2 rest
0.0
NCI-H292 IL-13
0.0


Two Way MLR 3 day
4.5
NCI-H292 IFN gamma
1.9


Two Way MLR 5 day
0.0
HPAEC none
0.0


Two Way MLR 7 day
0.0
HPAEC TNF alpha + IL-
0.0




1beta


PBMC rest
0.0
Lung fibroblast none
0.0


PBMC PWM
3.7
Lung fibroblast TNF
0.0




alpha + IL-1beta


PBMC PHA-L
0.0
Lung fibroblast IL-4
0.0


Ramos (B cell) none
0.0
Lung fibroblast IL-9
14.1


Ramos (B cell)
0.0
Lung fibroblast IL-13
4.3


ionomycin


B lymphocytes PWM
0.0
Lung fibroblast IFN
0.0




gamma


B lymphocytes CD40L
0.0
Dermal fibroblast
0.0


and IL-4

CCD1070 rest


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0




CCD1070 TNF alpha


EOL-1 dbcAMP
1.6
Dermal fibroblast
0.0


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
2.1
Dermal fibroblast IFN
0.0




gamma


Dendritic cells LPS
0.0
Dermal fibroblast IL-4
3.0


Dendritic cells anti-
2.5
IBD Colitis 2
0.0


CD40


Monocytes rest
0.0
IBD Crohn's
0.0


Monocytes LPS
0.0
Colon
100.0


Macrophages rest
0.0
Lung
29.3


Macrophages LPS
0.0
Thymus
0.0


HUVEC none
0.0
Kidney
2.4


HUVEC starved
0.0










[1346] AI_comprehensive panel_v1.0 Summary: Ag3311—Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1347] CNS_neurodegeneration_v1.0 Summary: Ag3311—Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1348] General_screening_panel_v1.4 Summary: Ag3311—Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1349] Panel 4D Summary: Ag3311—Significant expression of this gene is seen only in colon (CT=33.9). Therefore, expression of this gene can be used to distinguish between this sample and the others on the panel and between healthy and inflammed bowel. Since expression is not detectable in samples derived from Crohn's and colitis patients, therapeutic modulation of the expression or function of this gene may be useful in the treatment of inflammatory bowel disease.


[1350] V. CG58553-01: Vasolpressin Receptor


[1351] Expression of gene CG58553-01 was assessed using the primer-probe set Ag3372, described in Table VA. Results of the RTQ-PCR runs are shown in Tables VB and VC.


[1352] Table VA. Probe Name Ag3372
755TABLE VAProbe Name Ag3372StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-cggatctggtcatcacaca-3′191983457ProbeTET-5′-ccacccacaacctcccaaggaact-3′-TAMRA242017458Reverse5′-agcctcagaaggtcgagatg-3′202041459


[1353]

756





TABLE VB










Panel 1.3D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3372,

Ag3372,


Tissue Name
Run 165524269
Tissue Name
Run 165524269













Liver adenocarcinoma
0.7
Kidney (fetal)
0.0


Pancreas
0.2
Renal ca. 786-0
0.0


Pancreatic ca. CAPAN 2
0.0
Renal ca. A498
0.1


Adrenal gland
0.0
Renal ca. RXF 393
0.0


Thyroid
0.1
Renal ca. ACHN
0.0


Salivary gland
0.1
Renal ca. UO-31
0.0


Pituitary gland
0.2
Renal ca. TK-10
0.0


Brain (fetal)
0.0
Liver
2.1


Brain (whole)
0.3
Liver (fetal)
0.0


Brain (amygdala)
0.0
Liver ca.
0.2




(hepatoblast) HepG2


Brain (cerebellum)
0.1
Lung
2.4


Brain (hippocampus)
0.5
Lung (fetal)
0.2


Brain (substantia nigra)
0.2
Lung ca. (small cell)
0.0




LX-1


Brain (thalamus)
0.0
Lung ca. (small cell)
0.0




NCI-H69


Cerebral Cortex
0.0
Lung ca. (s.cell var.)
0.1




SHP-77


Spinal cord
1.0
Lung ca. (large
0.0




cell)NCI-H460


glio/astro U87-MG
0.0
Lung ca. (non-sm.
0.1




cell) A549


glio/astro U-118-MG
0.0
Lung ca. (non-s.cell)
0.6




NCI-H23


astrocytoma SW1783
0.0
Lung ca. (non-s.cell)
0.1




HOP-62


neuro*; met SK-N-AS
0.0
Lung ca. (non-s.cl)
0.0




NCI-H522


astrocytoma SF-539
0.0
Lung ca. (squam.)
0.0




SW 900


astrocytoma SNB-75
0.1
Lung ca. (squam.)
0.0




NCI-H596


glioma SNB-19
0.4
Mammary gland
0.7


glioma U251
0.2
Breast ca.* (pl.ef)
0.0




MCF-7


glioma SF-295
0.0
Breast ca.* (pl.ef)
0.0




MDA-MB-231


Heart (fetal)
0.0
Breast ca.* (pl.ef)
0.1




T47D


Heart
0.0
Breast ca. BT-549
0.0


Skeletal muscle (fetal)
0.0
Breast ca. MDA-N
0.0


Skeletal muscle
0.0
Ovary
0.0


Bone marrow
1.6
Ovarian ca.
0.2




OVCAR-3


Thymus
1.7
Ovarian ca.
0.0




OVCAR-4


Spleen
2.8
Ovarian ca.
0.2




OVCAR-5


Lymph node
5.5
Ovarian ca.
0.2




OVCAR-8


Colorectal
0.2
Ovarian ca. IGROV-1
0.0


Stomach
1.2
Ovarian ca.*
0.0




(ascites) SK-OV-3


Small intestine
100.0
Uterus
0.0


Colon ca. SW480
0.0
Placenta
0.8


Colon ca.*
0.0
Prostate
0.1


SW620(SW480 met)


Colon ca. HT29
0.0
Prostate ca.* (bone
0.0




met)PC-3


Colon ca. HCT-116
0.0
Testis
1.4


Colon ca. CaCo-2
0.3
Melanoma
0.0




Hs688(A).T


Colon ca.
0.7
Melanoma* (met)
0.0


tissue(ODO3866)

Hs688(B).T


Colon ca. HCC-2998
3.8
Melanoma UACC-
0.0




62


Gastric ca.* (liver met)
1.0
Melanoma M14
0.2


NCI-N87


Bladder
0.0
Melanoma LOX
0.2




IMVI


Trachea
0.1
Melanoma* (met)
0.4




SK-MEL-5


Kidney
0.6
Adipose
1.3










[1354]

757





TABLE VC










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3372, Run

Ag3372, Run


Tissue Name
165296616
Tissue Name
165296616













Secondary Th1 act
1.4
HUVEC IL-1beta
0.0


Secondary Th2 act
1.4
HUVEC IFN gamma
0.0


Secondary Tr1 act
2.9
HUVEC TNF alpha +
0.0




IFN gamma


Secondary Th1 rest
5.4
HUVEC TNF alpha +
0.0




IL4


Secondary Th2 rest
6.4
HUVEC IL-11
0.0


Secondary Tr1 rest
12.0
Lung Microvascular EC
0.0




none


Primary Th1 act
11.4
Lung Microvascular EC
0.0




TNF alpha + IL-1beta


Primary Th2 act
18.9
Microvascular Dermal
0.0




EC none


Primary Tr1 act
27.0
Microsvasular Dermal
0.0




EC TNF alpha + IL-1beta


Primary Th1 rest
27.5
Bronchial epithelium
0.1




TNF alpha + IL1beta


Primary Th2 rest
13.6
Small airway epithelium
0.0




none


Primary Tr1 rest
32.8
Small airway epithelium
0.0




TNF alpha + IL-1beta


CD45RA CD4
3.0
Coronery artery SMC rest
0.0


lymphocyte act


CD45RO CD4
8.5
Coronery artery SMC
0.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
5.8
Astrocytes rest
0.0


Secondary CD8
3.1
Astrocytes TNF alpha +
0.0


lymphocyte rest

IL-1beta


Secondary CD8
2.9
KU-812 (Basophil) rest
0.0


lymphocyte act


CD4 lymphocyte none
4.7
KU-812 (Basophil)
0.1




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
7.5
CCD1106
0.0


CD95 CH11

(Keratinocytes) none


LAK cells rest
1.8
CCD1106
0.0




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
5.8
Liver cirrhosis
1.5


LAK cells IL-2 + IL-12
2.3
Lupus kidney
0.6


LAK cells IL-2 + IFN
5.5
NCI-H292 none
2.5


gamma


LAK cells IL-2 + IL-18
5.5
NCI-H292 IL-4
1.8


LAK cells
2.7
NCI-H292 IL-9
5.9


PMA/ionomycin


NK Cells IL-2 rest
6.0
NCI-H292 IL-13
2.3


Two Way MLR 3 day
2.1
NCI-H292 IFN gamma
3.0


Two Way MLR 5 day
0.9
HPAEC none
0.0


Two Way MLR 7 day
1.8
HPAEC TNF alpha + IL-
0.0




1beta


PBMC rest
1.5
Lung fibroblast none
0.0


PBMC PWM
5.6
Lung fibroblast TNF
0.0




alpha + IL-1beta


PBMC PHA-L
0.9
Lung fibroblast IL-4
0.0


Ramos (B cell) none
0.0
Lung fibroblast IL-9
0.0


Ramos (B cell)
0.2
Lung fibroblast IL-13
0.0


ionomycin


B lymphocytes PWM
2.2
Lung fibroblast IFN
0.0




gamma


B lymphocytes CD40L
3.7
Dermal fibroblast
0.0


and IL-4

CCD1070 rest


EOL-1 dbcAMP
1.0
Dermal fibroblast
5.2




CCD1070 TNF alpha


EOL-1 dbcAMP
0.4
Dermal fibroblast
0.0


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
0.2
Dermal fibroblast IFN
0.1




gamma


Dendritic cells LPS
0.0
Dermal fibroblast IL-4
0.0


Dendritic cells anti-
0.0
IBD Colitis 2
0.4


CD40


Monocytes rest
0.3
IBD Crohn's
8.4


Monocytes LPS
0.2
Colon
100.0


Macrophages rest
0.7
Lung
0.9


Macrophages LPS
0.0
Thymus
8.1


HUVEC none
0.0
Kidney
6.8


HUVEC starved
0.0










[1355] Panel 1.3D Summary: Ag3372 Highest expression of the CG58553-01 gene is seen in the small intestine sample (CT=26.8). This gene encodes a novel vasopressin gene that plays a role in regulating electrolyte transport in the colon. Therefore, regulation of the transcript or the protein it encodes could be important in maintaining normal cellular homeostasis and in the treatment of Crohn's disease and ulcerative colitis.


[1356] Among tissues with metabolic function, this gene is expressed in liver and adipose. Thus, this gene product may be involved in disorders that affect these tissues, such as obesity and type II diabetes.


[1357] Low, but significant expression is also seen in the hippocampus. The hippocampus is critical for learning and memory. Thus, this gene product may have utility treating CNS disorders involving memory deficits, including Alzheimer's disease and aging.



REFERENCES

[1358] 1. Sato Y, Hanai H, Nogaki A, Hirasawa K, Kaneko E, Hayashi H, Suzuki Y. Role of the vasopressin V(1) receptor in regulating the epithelial functions of the guinea pig distal colon. Am J Physiol October 1999;277(4 Pt 1):G819-28.


[1359] Panel 4D Summary: Ag3372 In agreement with the results seen in panel 1.4, the highest level of expression of this gene is in the colon sample (CT=27.5). Interestingly, the expression is significantly lower in the IBD colitis 2 (CTh35) and IBD Crohn's (CT=30.9) samples. Therefore, alterations in the expression of this gene may be used in the treatment of Crohn's disease and ulcerative colitis.


[1360] In addition, the expression of the CG58553-01 gene in several preparations of T lymphocytes suggests that small molecule antagonists, therapeutic antibodies specific for this molecule, or the extracellular domain of this protein, may be useful to reduce or eliminate the symptoms of Crohn's disease, ulcerative colitis, multiple sclerosis, chronic obstructive pulmonary disease, asthma, emphysema, rheumatoid arthritis, lupus erythematosus, or psoriasis.


[1361] W. CG58626-01: Phospholipase


[1362] Expression of gene CG58626-01 was assessed using the primer-probe set Ag3386, described in Table WA. Results of the RTQ-PCR runs are shown in Tables WB, WC and WD.


[1363] Table WA. Probe Name Ag3386
758TABLE WAProbe Name Ag3386StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-agtggcggtcaaaacttactct-3′221386460ProbeTET-5′-tggagacactgttgattccattactcctg-3′-TAMRA291411461Reverse5′-ctgctgttcagcatatccctta-3′221455462


[1364]

759





TABLE WB










CNS_neurodegeneration_v1.0













Rel. Exp.



Rel. Exp. (%)

(%) Ag3386,



Ag3386, Run

Run


Tissue Name
210154893
Tissue Name
210154893













AD 1 Hippo
6.4
Control (Path) 3
4.2




Temporal Ctx


AD 2 Hippo
21.5
Control (Path) 4
25.0




Temporal Ctx


AD 3 Hippo
5.0
AD 1 Occipital
14.4




Ctx


AD 4 Hippo
5.3
AD 2 Occipital
0.0




Ctx (Missing)


AD 5 hippo
95.3
AD 3 Occipital
3.3




Ctx


AD 6 Hippo
51.1
AD 4 Occipital
18.7




Ctx


Control 2 Hippo
26.4
AD 5 Occipital
28.7




Ctx


Control 4 Hippo
4.5
AD 6 Occipital
52.5




Ctx


Control (Path) 3
4.0
Control 1 Occipital
2.4


Hippo

Ctx


AD 1 Temporal Ctx
13.5
Control 2 Occipital
56.3




Ctx


AD 2 Temporal Ctx
24.5
Control 3 Occipital
11.0




Ctx


AD 3 Temporal Ctx
3.8
Control 4 Occipital
4.3




Ctx


AD 4 Temporal Ctx
18.9
Control (Path) 1
100.0




Occipital Ctx


AD 5 Inf Temporal
95.9
Control (Path) 2
8.8


Ctx

Occipital Ctx


AD 5 Sup Temporal
37.6
Control (Path) 3
1.7


Ctx

Occipital Ctx


AD 6 Inf Temporal
52.5
Control (Path) 4
12.3


Ctx

Occipital Ctx


AD 6 Sup Temporal
63.7
Control 1 Parietal
5.4


Ctx

Ctx


Control 1 Temporal
4.9
Control 2 Parietal
39.5


Ctx

Ctx


Control 2 Temporal
38.4
Control 3 Parietal
11.3


Ctx

Ctx


Control 3 Temporal
12.2
Control (Path) 1
77.4


Ctx

Parietal Ctx


Control 4 Temporal
5.0
Control (Path) 2
20.7


Ctx

Parietal Ctx


Control (Path) 1
76.8
Control (Path) 3
2.7


Temporal Ctx

Parietal Ctx


Control (Path) 2
37.6
Control (Path) 4
45.4


Temporal Ctx

Parietal Ctx










[1365]

760





TABLE WC










General_screening_panel_v1.4











Rel. Exp.

Rel. Exp.



(%) Ag3386,

(%) Ag3386,



Run

Run


Tissue Name
217043839
Tissue Name
217043839













Adipose
12.2
Renal ca. TK-10
10.7


Melanoma*
26.4
Bladder
18.4


Hs688(A).T


Melanoma*
30.4
Gastric ca. (liver met.)
26.6


Hs688(B).T

NCI-N87


Melanoma* M14
13.1
Gastric ca. KATO III
0.0


Melanoma*
22.8
Colon ca. SW-948
10.8


LOXIMVI


Melanoma* SK-
22.7
Colon ca. SW480
40.9


MEL-5


Squamous cell
11.2
Colon ca.* (SW480
20.4


carcinoma SCC-4

met) SW620


Testis Pool
47.0
Colon ca. HT29
5.2


Prostate ca.* (bone
80.1
Colon ca. HCT-116
100.0


met) PC-3


Prostate Pool
7.1
Colon ca. CaCo-2
13.8


Placenta
3.2
Colon cancer tissue
13.6


Uterus Pool
6.4
Colon ca. SW1116
10.2


Ovarian ca.
22.8
Colon ca. Colo-205
1.8


OVCAR-3


Ovarian ca. SK-
94.0
Colon ca. SW-48
2.4


OV-3


Ovarian ca.
4.7
Colon Pool
27.7


OVCAR-4


Ovarian ca.
29.3
Small Intestine Pool
14.6


OVCAR-5


Ovarian ca.
12.7
Stomach Pool
12.2


IGROV-1


Ovarian ca.
11.1
Bone Marrow Pool
6.9


OVCAR-8


Ovary
11.6
Fetal Heart
8.1


Breast ca. MCF-7
36.9
Heart Pool
6.3


Breast ca. MDA-
39.5
Lymph Node Pool
13.9


MB-231


Breast ca. BT 549
28.5
Fetal Skeletal Muscle
3.6


Breast ca. T47D
52.9
Skeletal Muscle Pool
6.7


Breast ca. MDA-N
11.3
Spleen Pool
17.1


Breast Pool
28.1
Thymus Pool
26.1


Trachea
11.0
CNS cancer
33.2




(glio/astro) U87-MG


Lung
6.0
CNS cancer
44.1




(glio/astro) U-118-MG


Fetal Lung
39.2
CNS cancer
44.4




(neuro; met) SK-N-AS


Lung ca. NCI-N417
6.3
CNS cancer (astro)
10.4




SF-539


Lung ca. LX-1
33.9
CNS cancer (astro)
27.7




SNB-75


Lung ca. NCI-H146
14.3
CNS cancer (glio)
10.2




SNB-19


Lung ca. SHP-77
73.2
CNS cancer (glio) SF-
28.7




295


Lung ca. A549
25.3
Brain (Amygdala)
23.2




Pool


Lung ca. NCI-H526
5.8
Brain (cerebellum)
19.8


Lung ca. NCI-H23
30.1
Brain (fetal)
35.6


Lung ca. NCI-H460
20.2
Brain (Hippocampus)
25.2




Pool


Lung ca. HOP-62
11.9
Cerebral Cortex Pool
39.2


Lung ca. NCI-H522
20.7
Brain (Substantia
23.0




nigra) Pool


Liver
0.7
Brain (Thalamus) Pool
45.7


Fetal Liver
29.5
Brain (whole)
24.0


Liver ca. HepG2
10.1
Spinal Cord Pool
22.5


Kidney Pool
21.3
Adrenal Gland
8.5


Fetal Kidney
19.5
Pituitary gland Pool
7.0


Renal ca. 786-0
15.9
Salivary Gland
1.9


Renal ca. A498
3.5
Thyroid (female)
3.2


Renal ca. ACHN
8.0
Pancreatic ca.
3.7




CAPAN2


Renal ca. UO-31
12.2
Pancreas Pool
18.2










[1366]

761





TABLE WD










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3386, Run

Ag3386, Run


Tissue Name
165296474
Tissue Name
165296474













Secondary Th1 act
30.4
HUVEC IL-1beta
2.0


Secondary Th2 act
35.6
HUVEC IFN gamma
3.3


Secondary Tr1 act
27.9
HUVEC TNF alpha +
3.8




IFN gamma


Secondary Th1 rest
8.9
HUVEC TNF alpha +
3.3




IL4


Secondary Th2 rest
8.0
HUVEC IL-11
1.5


Secondary Tr1 rest
11.3
Lung Microvascular EC
5.5




none


Primary Th1 act
57.4
Lung Microvascular EC
4.8




TNF alpha + IL-1beta


Primary Th2 act
36.9
Microvascular Dermal
3.7




EC none


Primary Tr1 act
51.1
Microsvasular Dermal
3.3




EC TNF alpha + IL-1beta


Primary Th1 rest
54.0
Bronchial epithelium
5.5




TNF alpha + IL1beta


Primary Th2 rest
18.8
Small airway epithelium
2.1




none


Primary Tr1 rest
24.7
Small airway epithelium
6.1




TNF alpha + IL-1beta


CD45RA CD4
12.4
Coronery artery SMC rest
4.6


lymphocyte act


CD45RO CD4
33.9
Coronery artery SMC
2.4


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
29.3
Astrocytes rest
3.0


Secondary CD8
26.1
Astrocytes TNF alpha +
3.0


lymphocyte rest

IL-1beta


Secondary CD8
20.7
KU-812 (Basophil) rest
12.1


lymphocyte act


CD4 lymphocyte none
1.1
KU-812 (Basophil)
27.7




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
12.8
CCD1106
2.7


CD95 CH11

(Keratinocytes) none


LAK cells rest
12.0
CCD1106
0.8




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
24.3
Liver cirrhosis
0.3


LAK cells IL-2 + IL-12
28.7
Lupus kidney
0.7


LAK cells IL-2 + IFN
42.0
NCI-H292 none
8.1


gamma


LAK cells IL-2 + IL-18
45.1
NCI-H292 IL-4
9.5


LAK cells
8.8
NCI-H292 IL-9
8.5


PMA/ionomycin


NK Cells IL-2 rest
21.8
NCI-H292 IL-13
4.5


Two Way MLR 3 day
18.7
NCI-H292 IFN gamma
3.6


Two Way MLR 5 day
11.0
HPAEC none
2.5


Two Way MLR 7 day
10.9
HPAEC TNF alpha + IL-
3.0




1beta


PBMC rest
4.5
Lung fibroblast none
4.6


PBMC PWM
66.0
Lung fibroblast TNF
3.3




alpha + IL-1beta


PBMC PHA-L
17.9
Lung fibroblast IL-4
12.1


Ramos (B cell) none
26.1
Lung fibroblast IL-9
12.3


Ramos (B cell)
100.0
Lung fibroblast IL-13
6.7


ionomycin


B lymphocytes PWM
88.9
Lung fibroblast IFN
16.6




gamma


B lymphocytes CD40L
49.3
Dermal fibroblast
8.2


and IL-4

CCD1070 rest


EOL-1 dbcAMP
13.0
Dermal fibroblast
37.1




CCD1070 TNF alpha


EOL-1 dbcAMP
9.5
Dermal fibroblast
4.4


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
8.9
Dermal fibroblast IFN
6.0




gamma


Dendritic cells LPS
5.4
Dermal fibroblast IL-4
12.1


Dendritic cells anti-
4.3
IBD Colitis 2
0.7


CD40


Monocytes rest
4.7
IBD Crohn's
0.5


Monocytes LPS
2.6
Colon
3.4


Macrophages rest
8.8
Lung
4.9


Macrophages LPS
2.8
Thymus
4.1


HUVEC none
2.8
Kidney
13.0


HUVEC starved
6.4










[1367] CNS_neurodegeneration_v1.0 Summary: Ag3386 This panel confirms the expression of this gene at moderate to low levels in the brain in an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.


[1368] General_screening_panel_v1.4 Summary: Ag3386 This gene is moderately expressed in most of the samples on this panel. Based on expression in this panel, this gene may be involved in gastric, pancreatic, brain, colon, renal, lung, breast, ovarian and prostate cancer as well as melanomas. Thus, expression of this gene could be used as a diagnostic marker for the presence of these cancers. Furthermore, therapeutic inhibition using antibodies or small molecule drugs might be of use in the treatment of these cancers.


[1369] This gene product is also expressed in adipose, pancreas, adrenal, thyroid, pituitary, skeletal muscle, heart, and liver. This widespread expression in tissues with metabolic function suggests that this gene product may be important for the pathogenesis, diagnosis, and/or treatment of metabolic and endocrine diseases, including obesity and Types 1 and 2 diabetes.


[1370] In addition, this gene is expressed at moderate levels in the CNS. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[1371] Panel 4D Summary: Ag3386 The CG58626-01 transcript is expressed ubiquitously in this panel. Highest expression of this transcript is seen in activated Ramos cells and activated B cells (CTs=27). The expression of this transcript in activated lymphoid cells when compared to non activated cells suggests that the CG58626-01 gene may be important for the diagnosis or pathogenesis of immune mediated diseases. Therefore, modulation of the expression and/or activity of this gene product might important for the treatment of autoimmune diseases, allergy, and delayed type hypersensitivity.


[1372] X. CG57597-01: Hypothetical Protein


[1373] Expression of gene CG57597-01 was assessed using the primer-probe set Ag3293, described in Table XA.


[1374] Table XA. Probe Name Ag3293
762TABLE XAProbe Name Ag3293StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-cagaaacctgtgaactctgcat-3′2240463ProbeTET-5′-atgcaccaccactcctggctaatttt-3′-TAMRA2669464Reverse5′-ataaaaggtttgagccggatt-3′21115465


[1375] CNS_neurodegeneration_v1.0 Summary: Ag3293—Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1376] General_screening_panel_v1.4 Summary: Ag3293—Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1377] Panel 4D Summary: Ag3293—Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1378] Y. CG57804-01: talin


[1379] Expression of gene CG57804-01 was assessed using the primer-probe set Ag3337, described in Table YA. Results of the RTQ-PCR runs are shown in Tables YB, YC and YD.


[1380] Table YA. Probe Name Ag3337
763TABLE YAProbe Name Ag3337StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-ggatttcaagcccagatacaat-3′22781466ProbeTET-5′-tggacctcatgtggaacataaacaca-3′-TAMRA26804467Reverse5′-ggcaggaattccttcagatc-3′20844468


[1381]

764





TABLE YB










CNS_neurodegeneration_v1.0













Rel. Exp.



Rel. Exp. (%)

(%) Ag3337,



Ag3337, Run

Run


Tissue Name
210138775
Tissue Name
210138775













AD 1 Hippo
6.8
Control (Path) 3
3.6




Temporal Ctx


AD 2 Hippo
25.3
Control (Path) 4
22.4




Temporal Ctx


AD 3 Hippo
3.6
AD 1 Occipital Ctx
5.6


AD 4 Hippo
5.7
AD 2 Occipital Ctx
0.0




(Missing)


AD 5 Hippo
78.5
AD 3 Occipital Ctx
2.2


AD 6 Hippo
27.5
AD 4 Occipital Ctx
14.7


Control 2 Hippo
27.4
AD 5 Occipital Ctx
44.1


Control 4 Hippo
8.1
AD 6 Occipital Ctx
16.6


Control (Path) 3
4.3
Control 1 Occipital
1.6


Hippo

Ctx


AD 1 Temporal
7.6
Control 2 Occipital
67.8


Ctx

Ctx


AD 2 Temporal
24.5
Control 3 Occipital
11.9


Ctx

Ctx


AD 3 Temporal
3.3
Control 4 Occipital
3.0


Ctx

Ctx


AD 4 Temporal
15.3
Control (Path) 1
89.5


Ctx

Occipital Ctx


AD 5 Inf Temporal
89.5
Control (Path) 2
8.2


Ctx

Occipital Ctx


AD 5 Sup Temporal
35.8
Control (Path) 3
0.6


Ctx

Occipital Ctx


AD 6 Inf Temporal
27.4
Control (Path) 4
10.3


Ctx

Occipital Ctx


AD 6 Sup
32.8
Control 1 Parietal
3.6


Temporal Ctx

Ctx


Control 1
3.4
Control 2 Parietal
23.7


Temporal Ctx

Ctx


Control 2
47.6
Control 3 Parietal
14.1


Temporal Ctx

Ctx


Control 3
12.4
Control (Path) 1
100.0


Temporal Ctx

Parietal Ctx


Control 3
5.8
Control (Path) 2
21.9


Temporal Ctx

Parietal Ctx


Control (Path) 1
64.2
Control (Path) 3
2.0


Temporal Ctx

Parietal Ctx


Control (Path) 2
42.0
Control (Path) 4
39.2


Temporal Ctx

Parietal Ctx










[1382]

765





TABLE YC










General_screening_panel_v1.4











Rel. Exp.

Rel. Exp.



(%) Ag3337,

(%) Ag3337,



Run

Run


Tissue Name
215773748
Tissue Name
215773748













Adipose
20.2
Renal ca. TK-10
22.1


Melanoma*
58.6
Bladder
14.2


Hs688(A).T


Melanoma*
22.8
Gastric ca. (liver met.)
16.2


Hs688(B).T

NCI-N87


Melanoma* M14
5.7
Gastric ca. KATO
100.0




III


Melanoma*
5.5
Colon ca. SW-
16.3


LOXIMVI

948


Melanoma* SK-
3.4
Colon ca. SW480
4.2


MEL-5


Squamous cell
4.4
Colon ca.* (SW480
2.6


carcinoma SCC-4

met) SW620


Testis Pool
5.1
Colon ca. HT29
0.7


Prostate ca.* (bone
6.4
Colon ca. HCT-116
7.6


met) PC-3



Prostate Pool
3.4
Colon ca. CaCo-2
81.8


Placenta
1.6
Colon cancer tissue
1.7


Uterus Pool
2.1
Colon ca. SW1116
1.6


Ovarian ca.
8.9
Colon ca. Colo-205
0.1


OVCAR-3


Ovarian ca. SK-
32.1
Colon ca. SW-48
3.2


OV-3


Ovarian ca.
7.2
Colon Pool
8.0


OVCAR-4


Ovarian ca.
21.0
Small Intestine Pool
7.9


OVCAR-5


Ovarian ca.
23.5
Stomach Pool
5.7


IGROV-1


Ovarian ca.
5.4
Bone Marrow Pool
3.8


OVCAR-8


Ovary
11.7
Fetal Heart
24.8


Breast ca. MCF-7
5.1
Heart Pool
10.2


Breast ca. MDA-
19.5
Lymph Node Pool
10.6


MB-231


Breast ca. BT 549
11.7
Fetal Skeletal Muscle
30.1


Breast ca. T47D
30.8
Skeletal Muscle Pool
24.8


Breast ca. MDA-N
5.0
Spleen Pool
2.9


Breast Pool
6.9
Thymus Pool
0.0


Trachea
10.3
CNS cancer
10.7




(glio/astro) U87-MG


Lung
2.2
CNS cancer
68.3




(glio/astro) U-118-MG


Fetal Lung
10.8
CNS cancer
23.5




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.8
CNS cancer (astro)
21.5




SF-539


Lung ca. LX-1
1.7
CNS cancer (astro)
40.3




SNB-75


Lung ca. NCI-H146
0.4
CNS cancer (glio)
27.7




SNB-19


Lung ca. SHP-77
11.9
CNS cancer (glio) SF-
38.2




295


Lung ca. A549
13.6
Brain (Amygdala)
28.7




Pool


Lung ca. NCI-H526
7.6
Brain (cerebellum)
38.7


Lung ca. NCI-H23
10.2
Brain (fetal)
58.6


Lung ca. NCI-H460
5.1
Brain (Hippocampus)
25.7




Pool


Lung ca. HOP-62
3.8
Cerebral Cortex Pool
59.0


Lung ca. NCI-H522
10.1
Brain (Substantia
39.2




nigra) Pool


Liver
0.3
Brain (Thalamus) Pool
51.4


Fetal Liver
15.3
Brain (whole)
58.2


Liver ca. HepG2
53.2
Spinal Cord Pool
18.6


Kidney Pool
18.4
Adrenal Gland
11.1


Fetal Kidney
11.4
Pituitary gland Pool
4.7


Renal ca. 786-0
31.0
Salivary Gland
14.0


Renal ca. A498
0.7
Thyroid (female)
4.9


Renal ca. ACHN
20.3
Pancreatic ca.
7.5




CAPAN2


Renal ca. UO-31
8.1
Pancreas Pool
9.4










[1383]

766





TABLE YD










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3337, Run

Ag3337, Run


Tissue Name
165725932
Tissue Name
165725932













Secondary Th1 act
0.0
HUVEC IL-1beta
0.7


Secondary Th2 act
0.0
HUVEC IFN gamma
3.9


Secondary Tr1 act
0.4
HUVEC TNF alpha +
0.3




IFN gamma


Secondary Th1 rest
0.4
HUVEC TNF alpha +
0.6




IL4


Secondary Th2 rest
0.0
HUVEC IL-11
0.3


Secondary Tr1 rest
0.3
Lung Microvascular EC
2.1




none


Primary Th1 act
0.3
Lung Microvascular EC
5.1




TNF alpha + IL-1beta


Primary Th2 act
1.3
Microvascular Dermal
16.4




EC none


Primary Tr1 act
0.6
Microsvasular Dermal
9.8




EC TNF alpha + IL-1beta


Primary Th1 rest
1.3
Bronchial epithelium
1.2




TNF alpha + IL1beta


Primary Th2 rest
0.6
Small airway epithelium
1.3




none


Primary Tr1 rest
0.3
Small airway epithelium
2.1




TNF alpha + IL-1beta


CD45RA CD4
18.7
Coronery artery SMC rest
9.9


lymphocyte act


CD45RO CD4
0.6
Coronery artery SMC
3.5


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
1.2
Astrocytes rest
100.0


Secondary CD8
0.9
Astrocytes TNF alpha +
65.5


lymphocyte rest

IL-1beta


Secondary CD8
0.2
KU-812 (Basophil) rest
11.7


lymphocyte act


CD4 lymphocyte none
0.0
KU-812 (Basophil)
8.5




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
0.3
CCD1106
2.0


CD95 CH11

(Keratinocytes) none


LAK cells rest
4.0
CCD1106
2.0




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
1.2
Liver cirrhosis
3.6


LAK cells IL-2 + IL-12
0.4
Lupus Kidney
13.6


LAK cells IL-2 + IFN
2.1
NCI-H292 none
11.0


gamma


LAK cells IL-2 + IL-18
1.2
NCI-H292 IL-4
25.0


LAK cells
2.0
NCI-H292 IL-9
15.6


PMA/ionomycin


NK Cells IL-2 rest
0.0
NCI-H292 IL-13
12.5


Two Way MLR 3 day
5.2
NCI-H292 IFN gamma
4.6


Two Way MLR 5 day
2.7
HPAEC none
1.5


Two Way MLR 7 day
1.8
HPAEC TNF alpha + IL-
2.5




1beta


PBMC rest
0.2
Lung fibroblast none
80.1


PBMC PWM
1.9
Lung fibroblast TNF
22.7




alpha + IL-1beta


PBMC PHA-L
0.3
Lung fibroblast IL-4
97.3


Ramos (B cell) none
2.4
Lung fibroblast IL-9
47.6


Ramos (B cell)
2.1
Lung fibroblast IL-13
81.8


ionomycin


B lymphocytes PWM
0.7
Lung fibroblast IFN
50.7




gamma


B lymphocytes CD40L
0.6
Dermal fibroblast
94.6


and IL-4

CCD1070 rest


EOL-1 dbcAMP
4.9
Dermal fibroblast
43.2




CCD1070 TNF alpha


EOL-1 dbcAMP
1.2
Dermal fibroblast
31.2


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
12.8
Dermal fibroblast IFN
14.2




gamma


Dendritic cells LPS
1.3
Dermal fibroblast IL-4
95.9


Dendritic cells anti-
11.4
IBD Colitis 2
1.2


CD40


Monocytes rest
0.5
IBD Crohn's
9.1


Monocytes LPS
1.3
Colon
60.7


Macrophages rest
13.6
Lung
8.0


Macrophages LPS
2.8
Thymus
39.2


HUVEC none
1.0
Kidney
10.4


HUVEC starved
1.6










[1384] CNS_neurodegeneration_v1.0 Summary: Ag3337—This panel confirms the expression of this gene at low to moderate levels in the brain in an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of the potential utility of this gene in treatment of central nervous system disorders


[1385] General_screening_panel_v1.4 Summary: Ag3337—This gene is expressed in almost all samples on this panel. This gene is expressed at moderate levels in the CNS. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[1386] In addition, this gene is also expressed in adipose, pancreas, adrenal, thyroid, pituitary, skeletal muscle, heart, and liver. This widespread expression in tissues with metabolic function suggests that this gene product may be important for the pathogenesis, diagnosis, and/or treatment of metabolic and endocrine diseases, including obesity and Types 1 and 2 diabetes.


[1387] Panel 4D Summary: Ag3337 This gene is most highly expressed in resting astrocytes (CT=28.9). In addition, this gene is highly expressed in a cluster of treated and untreated samples derived from lung and dermal fibroblasts. Thus, therapeutic modulation of the expression or function of this gene may be effective in the treatment of pathological and inflammatory lung and skin diseases, such as psoriasis, asthma, emphysema, and allergies.


[1388] Z. CG57551-01: NAC-1 Like Gene


[1389] Expression of gene CG57551-01 was assessed using the primer-probe set Ag3282, described in Table ZA. Results of the RTQ-PCR runs are shown in Tables ZB, ZC and ZD.


[1390] Table ZA. Probe Name Ag3282
767TABLE ZAProbe Name Ag3282StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-cagatcctcagcttctgctaca-3′22269469ProbeTET-5′-accagttcctgctcatgtacacggct-3′-TAMRA26318470Reverse5′-atctcctggatctgcaggaa-3′20347471


[1391]

768





TABLE ZB










CNS_neurodegeneration_v1.0











Rel. Exp. (%) Ag3282,

Rel. Exp. (%) Ag3282,


Tissue Name
Run 210060482
Tissue Name
Run 210060482













AD 1 Hippo
22.8
Control (Path) 3
9.7




Temporal Ctx


AD 2 Hippo
49.0
Control (Path) 4
24.3




Temporal Ctx


AD 3 Hippo
11.5
AD 1 Occipital
16.5




Ctx


AD 4 Hippo
12.3
AD 2 Occipital
0.0




Ctx (Missing)


AD 5 hippo
66.9
AD 3 Occipital
10.2




Ctx


AD 6 Hippo
59.9
AD 4 Occipital
18.2




Ctx


Control 2 Hippo
49.3
AD 5 Occipital
9.5




Ctx


Control 4 Hippo
18.7
AD 6 Occipital
41.5




Ctx


Control (Path) 3
6.3
Control 1 Occipital
6.8


Hippo

Ctx


AD 1 Temporal Ctx
19.2
Control 2 Occipital
91.4




Ctx


AD 2 Temporal Ctx
40.3
Control 3 Occipital
16.3




Ctx


AD 3 Temporal Ctx
14.3
Control 4 Occipital
12.2




Ctx


AD 4 Temporal Ctx
18.3
Control (Path) 1
100.0




Occipital Ctx


AD 5 Inf Temporal
66.0
Control (Path) 2
9.2


Ctx

Occipital Ctx


AD 5 SupTemporal
37.4
Control (Path) 3
5.3


Ctx

Occipital Ctx


AD 6 Inf Temporal
36.1
Control (Path) 4
15.8


Ctx

Occipital Ctx


AD 6 Sup Temporal
34.4
Control 1 Parietal
11.7


Ctx

Ctx


Control 1 Temporal
10.0
Control 2 Parietal
34.2


Ctx

Ctx


Control 2 Temporal
74.7
Control 3 Parietal
23.3


Ctx

Ctx


Control 3 Temporal
15.0
Control (Path) 1
72.7


Ctx

Parietal Ctx


Control 4 Temporal
15.5
Control (Path) 2
21.6


Ctx

Parietal Ctx


Control (Path) 1
74.2
Control (Path) 3
5.5


Temporal Ctx

Parietal Ctx


Control (Path) 2
31.2
Control (Path) 4
35.8


Temporal Ctx

Parietal Ctx










[1392]

769





TABLE ZC










General_screening_panel_v1.4











Rel. Exp. (%) Ag3282, Run

Rel. Exp. (%) Ag3282, Run


Tissue Name
216512995
Tissue Name
216512995













Adipose
1.8
Renal ca. TK-10
22.7


Melanoma*
16.3
Bladder
6.3


Hs688(A).T


Melanoma*
25.0
Gastric ca. (liver met.)
47.0


Hs688(B).T

NCI-N87


Melanoma* M14
25.3
Gastric ca. KATO III
45.7


Melanoma*
21.6
Colon ca. SW-948
19.3


LOXIMVI


Melanoma* SK-
17.0
Colon ca. SW480
50.3


MEL-5


Squamous cell
24.7
Colon ca.* (SW480
25.9


carcinoma SCC-4

met) SW620


Testis Pool
6.1
Colon ca. HT29
17.7


Prostate ca.* (bone
67.8
Colon ca. HCT-116
100.0


met) PC-3


Prostate Pool
3.5
Colon ca. CaCo-2
29.1


Placenta
9.6
Colon cancer tissue
14.0


Uterus Pool
0.6
Colon ca. SW1116
12.7


Ovarian ca.
41.2
Colon ca. Colo-205
7.6


OVCAR-3


Ovarian ca. SK-
65.5
Colon ca. SW-48
5.8


OV-3


Ovarian ca.
35.8
Colon Pool
4.9


OVCAR-4


Ovarian ca.
37.6
Small Intestine Pool
2.4


OVCAR-5


Ovarian ca.
28.9
Stomach Pool
3.3


IGROV-1


Ovarian ca.
14.2
Bone Marrow Pool
1.5


OVCAR-8


Ovary
3.9
Fetal Heart
3.0


Breast ca. MCF-7
42.3
Heart Pool
2.2


Breast ca. MDA-
69.7
Lymph Node Pool
5.6


MB-231


Breast ca. BT 549
51.4
Fetal Skeletal Muscle
1.5


Breast ca. T47D
86.5
Skeletal Muscle Pool
0.0


Breast ca. MDA-N
26.4
Spleen Pool
2.8


Breast Pool
4.6
Thymus Pool
3.8


Trachea
8.7
CNS cancer
60.3




(glio/astro) U87-MG


Lung
0.2
CNS cancer
100.0




(glio/astro) U-118-MG


Fetal Lung
6.3
CNS cancer
47.3




(neuro; met) SK-N-AS


Lung ca. NCI-N417
8.4
CNS cancer (astro) SF-
22.8




539


Lung ca. LX-1
17.3
CNS cancer (astro)
47.3




SNB-75


Lung ca. NCI-H146
15.3
CNS cancer (glio)
29.3




SNB-19


Lung ca. SHP-77
16.5
CNS cancer (glio) SF-
49.3




295


Lung ca. A549
27.2
Brain (Amygdala) Pool
6.9


Lung ca. NCI-H526
6.1
Brain (cerebellum)
15.1


Lung ca. NCI-H23
25.9
Brain (fetal)
9.2


Lung ca. NCI-H460
8.0
Brain (Hippocampus)
8.9




Pool


Lung ca. HOP-62
11.9
Cerebral Cortex Pool
13.4


Lung ca. NCI-H522
21.9
Brain (Substantia
15.3




nigra) Pool


Liver
1.7
Brain (Thalamus) Pool
11.5


Fetal Liver
9.8
Brain (whole)
12.6


Liver ca. HepG2
18.2
Spinal Cord Pool
7.1


Kidney Pool
5.0
Adrenal Gland
5.3


Fetal Kidney
3.4
Pituitary gland Pool
1.9


Renal ca. 786-0
42.0
Salivary Gland
4.0


Renal ca. A498
16.7
Thyroid (female)
3.6


Renal ca. ACHN
13.9
Pancreatic ca.
15.5




CAPAN2


Real ca. UO-31
17.4
Pancreas Pool
6.6










[1393]

770





TABLE ZD










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3282, Run

Ag3282, Run


Tissue Name
164634321
Tissue Name
164634321













Secondary Th1 act
52.9
HUVEC IL-1beta
13.6


Secondary Th2 act
67.8
HUVEC IFN gamma
42.9


Secondary Tr1 act
75.3
HUVEC TNF alpha +
37.1




IFN gamma


Secondary Th1 rest
8.4
HUVEC TNF alpha +
42.6




IL4


Secondary Th2 rest
11.4
HUVEC IL-11
25.9


Secondary Tr1 rest
12.2
Lung Microvascular EC
41.2




none


Primary Th1 act
53.6
Lung Microvascular EC
36.3




TNF alpha + IL-1beta


Primary Th2 act
44.4
Microvascular Dermal
50.3




EC none


Primary Tr1 act
60.7
Microsvasular Dermal
33.0




EC TNF alpha + IL-1beta


Primary Th1 rest
37.6
Bronchial epithelium
51.4




TNF alpha + IL1beta


Primary Th2 rest
15.8
Small airway epithelium
23.3




none


Primary Tr1 rest
18.3
Small airway epithelium
71.7




TNF alpha + IL-1beta


CD45RA CD4
33.0
Coronery artery SMC rest
43.5


lymphocyte act


CD45RO CD4
54.7
Coronery artery SMC
31.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
42.9
Astrocytes rest
38.4


Secondary CD8
50.3
Astrocytes TNF alpha +
37.1


lymphocyte rest

IL-1beta


Secondary CD8
32.5
KU-812 (Basophil) rest
36.1


lymphocyte act


CD4 lymphocyte none
2.4
KU-812 (Basophil)
90.8




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
11.7
CCD1106
64.2


CD95 CH11

(Keratinocytes) none


LAK cells rest
18.9
CCD1106
34.4




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
41.2
Liver cirrhosis
2.9


LAK cells IL-2 + IL-12
29.5
Lupus kidney
2.2


LAK cells IL-2 + IFN
36.3
NCI-H292 none
38.4


gamma


LAK cells IL-2 + IL-18
34.2
NCI-H292 IL-4
66.9


LAK cells
11.8
NCI-H292 IL-9
62.4


PMA/ionomycin


NK Cells IL-2 rest
29.3
NCI-H292 IL-13
65.1


Two Way MLR 3 day
21.9
NCI-H292 IFN gamma
48.3


Two Way MLR 5 day
27.7
HPAEC none
31.2


Two Way MLR 7 day
27.0
HPAEC TNF alpha + IL-
37.6




1beta


PBMC rest
6.5
Lung fibroblast none
35.6


PBMC PWM
89.5
Lung fibroblast TNF
20.7




alpha + IL-1beta


PBMC PHA-L
53.6
Lung fibroblast IL-4
63.3


Ramos (B cell) none
40.6
Lung fibroblast IL-9
55.5


Ramos (B cell)
56.3
Lung fibroblast IL-13
44.8


ionomycin


B lymphocytes PWM
100.0
Lung fibroblast IFN
71.2




gamma


B lymphocytes CD40L
41.2
Dermal fibroblast
78.5


and IL-4

CCD1070 rest


EOL-1 dbcAMP
50.0
Dermal fibroblast
88.9




CCD1070 TNF alpha


EOL-1 dbcAMP
46.3
Dermal fibroblast
49.7


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
33.2
Dermal fibroblast IFN
21.5




gamma


Dendritic cells LPS
26.1
Dermal fibroblast IL-4
43.8


Dendritic cells anti-
29.9
IBD Colitis 2
1.2


CD40


Monocytes rest
17.1
IBD Crohn's
1.8


Monocytes LPS
14.0
Colon
15.4


Macrophages rest
59.0
Lung
16.6


Macrophages LPS
29.1
Thymus
15.6


HUVEC none
35.1
Kidney
18.9


HUVEC starved
62.0










[1394] CNS_neurodegeneration_v1.0 Summary: Ag3282—This panel confirms the expression of this gene at low levels in the brain in an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.


[1395] General_screening_panel_v1.4 Summary: Ag3282 Highest expression of this gene is seen in a brain cancer cell line (CT=24.3). This gene appears to be expressed more highly in the cancer cell lines than in the normal tissue samples on this panel and may be involved in cellular growth and proliferation. Based on this expression profile, this gene may be involved in gastric, pancreatic, brain, colon, renal, lung, breast, ovarian and prostate cancer as well as melanomas. Thus, expression of this gene could be used as a diagnostic marker for the presence of these cancers. Furthermore, therapeutic inhibition using antibodies or small molecule drugs might be of use in the treatment of these cancers.


[1396] This gene is also expressed at high levels in all regions of the CNS examined. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[1397] In addition, this gene product is expressed in adipose, pancreas, adrenal, thyroid, pituitary, fetal skeletal muscle, heart, and liver. This widespread expression in tissues with metabolic function suggests that this gene product may be important for the pathogenesis, diagnosis, and/or treatment of metabolic and endocrine diseases, including obesity and Types 1 and 2 diabetes.


[1398] Furthermore, this gene is more highly expressed in fetal skeletal muscle (CT=30.4) and liver (CT=27) when compared to expression in the adult skeletal muscle (CT>35) and liver (CT=30) may be useful for the differentiation of the fetal and adult sources of this tissue.


[1399] Panel 4D Summary: Ag3282 This gene is expressed at high to moderate levels in a wide range of cell types of significance in the immune response in health and disease. Highest expression is seen in polkweed mitogen stimulated B lymphocytes (CT=25.7). In addition, expression is seen in members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in Panel 1.4 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.


[1400] AA. CG57411-01: Kelch-Like Protein KLHL3C


[1401] Expression of gene CG57411-01 was assessed using the primer-probe set Ag3229, described in Table AAA. Results of the RTQ-PCR runs are shown in Tables AAB, AAC, AAD and AAE.


[1402] Table AAA. Probe Name Ag3229
771TABLE AAAProbe Name Ag3229StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-gcagcgagctctaccacat-3′19287472ProbeTET-5′-aaggccttcgcgctgcagatctt-3′-TAMRA23310473Reverse5′-aagtcgtccttggagatgct-3′20364474


[1403]

772





TABLE AAB










CNS_neurodegeneration_v1.0











Rel. Exp. (%) Ag3229,

Rel. Exp. (%) Ag3229,


Tissue Name
Run 209862301
Tissue Name
Run 209862301













AD 1 Hippo
16.3
Control (Path) 3
8.0




Temporal Ctx


AD 2 Hippo
34.6
Control (Path) 4
35.8




Temporal Ctx


AD 3 Hippo
15.9
AD 1 Occipital Ctx
18.6


AD 4 Hippo
6.9
AD 2 Occipital Ctx
0.0




(Missing)


AD 5 Hippo
100.0
AD 3 Occipital Ctx
11.7


AD 6 Hippo
35.4
AD 4 Occipital Ctx
17.7


Control 2 Hippo
31.2
AD 5 Occipital Ctx
49.7


Control 4 Hippo
12.1
AD 6 Occipital Ctx
14.2


Control (Path) 3
6.2
Control 1 Occipital
3.3


Hippo

Ctx


AD 1 Temporal
21.6
Control 2 Occipital
69.3


Ctx

Ctx


AD 2 Temporal
33.0
Control 3 Occipital
26.6


Ctx

Ctx


AD 3 Temporal
14.1
Control 4 Occipital
7.5


Ctx

Ctx


AD 4 Temporal
16.8
Control (Path) 1
72.2


Ctx

Occipital Ctx


AD 5 Inf Temporal
71.7
Control (Path) 2
13.7


Ctx

Occipital Ctx


AD 5 Sup
32.3
Control (Path) 3
6.3


Temporal Ctx

Occipital Ctx


AD 6 Inf Temporal
30.6
Control (Path) 4
16.8


Ctx

Occipital Ctx


AD 6 Sup
33.9
Control 1 Parietal
8.6


Temporal Ctx

Ctx


Control 1
4.4
Control 2 Parietal
39.8


Temporal Ctx

Ctx


Control 2
56.6
Control 3 Parietal
21.5


Temporal Ctx

Ctx


Control 3
19.6
Control (Path) 1
66.4


Temporal Ctx

Parietal Ctx


Control 3
14.2
Control (Path) 2
26.8


Temporal Ctx

Parietal Ctx


Control (Path) 1
62.0
Control (Path) 3
5.2


Temporal Ctx

Parietal Ctx


Control (Path) 2
36.1
Control (Path) 4
54.3


Temporal Ctx

Parietal Ctx










[1404]

773





TABLE AAC










General_screening_panel_v1.4

















Rel. Exp. (%) Ag3229, Run

Rel. Exp. (%) Ag3229, Run


Tissue Name
214439727
Tissue Name
214439727













Adipose
6.0
Renal ca. TK-10
20.4


Melanoma*
8.1
Bladder
6.7


Hs688(A).T


Melanoma*
13.5
Gastric ca. (liver met.)
11.2


Hs688(B).T

NCI-N87


Melanoma* M14
2.1
Gastric ca. KATO III
59.5


Melanoma*
24.8
Colon ca. SW-948
0.6


LOXIMVI


Melanoma* SK-
20.7
Colon ca. SW480
31.6


MEL-5


Squamous cell
6.7
Colon ca.* (SW480
4.7


carcinoma SCC-4

met) SW620


Testis Pool
3.0
Colon ca. HT29
2.7


Prostate ca.* (bone
17.8
Colon ca. HCT-116
35.1


met) PC-3


Prostate Pool
8.5
Colon ca. CaCo-2
2.5


Placenta
14.2
Colon cancer tissue
6.2


Uterus Pool
5.8
Colon ca. SW1116
3.3


Ovarian ca.
40.9
Colon ca. Colo-205
5.4


OVCAR-3


Ovarian ca. SK-
17.7
Colon ca. SW-48
3.3


OV-3


Ovarian ca.
11.9
Colon Pool
25.0


OVCAR-4


Ovarian ca.
84.1
Small Intestine Pool
14.9


OVCAR-5


Ovarian ca.
2.0
Stomach Pool
6.4


IGROV-1


Ovarian ca.
8.1
Bone Marrow Pool
9.7


OVCAR-8


Ovary
8.7
Fetal Heart
1.7


Breast ca. MCF-7
0.9
Heart Pool
10.7


Breast ca. MDA-
30.1
Lymph Node Pool
21.8


MB-231


Breast ca. BT 549
8.1
Fetal Skeletal Muscle
4.2


Breast ca. T47D
100.0
Skeletal Muscle Pool
8.7


Breast ca. MDA-N
0.0
Spleen Pool
10.4


Breast Pool
22.4
Thymus pool
11.2


Trachea
10.4
CNS cancer
55.5




(glio/astro) U87-MG


Lung
1.7
CNS cancer
44.8




(glio/astro) U-118-MG


Fetal Lung
6.7
CNS cancer
5.8




(neuro; met) SK-N-AS


Lung ca. NCI-N417
11.7
CNS cancer (astro) SF-
0.4




539


Lung ca. LX-1
37.1
CNS cancer (astro)
5.0




SNB-75


Lung ca. NCI-H146
6.2
CNS cancer (glio)
2.9




SNB-19


Lung ca. SHP-77
61.1
CNS cancer (glio) SF-
39.0




295


Lung ca. A549
6.3
Brain (Amygdala) Pool
8.4


Lung ca. NCI-H526
8.7
Brain (cerebellum)
22.2


Lung ca. NCI-H23
6.3
Brain (fetal)
48.6


Lung ca. NCI-H460
2.9
Brain (Hippocampus)
8.5




Pool


Lung ca. HOP-62
8.1
Cerebral Cortex Pool
20.7


Lung ca. NCI-H522
0.5
Brain (Substantia
14.7




nigra) Pool


Liver
0.3
Brain (Thalamus) Pool
13.8


Fetal Liver
1.8
Brain (whole)
11.5


Liver ca. HepG2
0.2
Spinal Cord Pool
3.3


Kidney Pool
26.8
Adrenal Gland
29.9


Fetal Kidney
10.2
Pituitary gland Pool
10.7


Renal ca. 786-0
7.5
Salivary Gland
4.1


Renal ca. A498
4.0
Thyroid (female)
1.1


Renal ca. ACHN
11.9
Pancreatic ca.
1.0




CAPAN2


Renal ca. UO-31
15.3
Pancreas Pool
28.7










[1405]

774





TABLE AAD










Panel 2.2











Rel. Exp. (%) Ag3229, Run

Rel. Exp. (%) Ag3229, Run


Tissue Name
174442765
Tissue Name
174442765













Normal Colon
15.5
Kidney Margin
100.0




(OD04348)


Colon cancer
31.9
Kidney malignant
10.7


(OD06064)

cancer (OD06204B)


Colon Margin
20.6
Kidney normal
11.6


(OD06064)

adjacent tissue




(OD06204E)


Colon cancer
6.0
Kidney Cancer
38.4


(OD06159)

(OD04450-01)


Colon Margin
12.7
Kidney Margin
17.4


(OD06159)

(OD04450-03)


Colon cancer
3.7
Kidney Cancer
0.0


(OD06297-04)

8120613


Colon Margin
22.4
Kidney Margin
6.0


(OD06297-05)

8120614


CC Gr.2 ascend colon
6.5
Kidney Cancer
12.0


(ODO3921)

9010320


CC Margin (ODO3921)
10.5
Kidney Margin
9.9




9010321


Colon cancer metastasis
8.6
Kidney Cancer
47.3


(OD06104)

8120607


Lung Margin
6.2
Kidney Margin
5.6


(OD06104)

8120608


Colon mets to lung
31.0
Normal Uterus
48.3


(OD04451-01)


Lung Margin
39.5
Uterine Cancer 064011
14.9


(OD04451-02)


Normal Prostate
41.2
Normal Thyroid
2.6


Prostate Cancer
8.1
Thyroid Cancer
4.3


(OD04410)

064010


Prostate Margin
10.6
Thyroid Cancer
15.3


(OD04410)

A302152


Normal Ovary
23.2
Thyroid Margin
2.7




A302153


Ovarian cancer
7.2
Normal Breast
46.0


(OD06283-03)


Ovarian Margin
17.8
Breast Cancer
5.9


(OD06283-07)

(OD04566)


Ovarian Cancer 064008
22.2
Breast Cancer 1024
27.4


Ovarian cancer
9.0
Breast Cancer
19.5


(OD06145)

(OD04590-01)


Ovarian Margin
13.4
Breast Cancer Mets
13.5


(OD06145)

(OD04590-03)


Ovarian cancer
6.3
Breast Cancer
12.2


(OD06455-03)

Metastasis (OD04655-




05)


Ovarian Margin
12.9
Breast Cancer 064006
8.1


(OD06455-07)


Normal Lung
14.5
Breast Cancer 9100266
3.0


Invasive poor diff. lung
5.0
Breast Margin
3.4


adeno (ODO4945-01)

9100265


Lung Margin
37.4
Breast Cancer
11.2


(ODO4945-03)

A209073


Lung Malignant Cancer
9.6
Breast Margin
61.1


(OD03126)

A2090734


Lung Margin
14.2
Breast cancer
4.7


(OD03126)

(OD06083)


Lung Cancer
4.9
Breast cancer node
12.7


(OD05014A)

metastasis (OD06083)


Lung Margin
39.0
Normal Liver
2.8


(OD05014B)


Lung cancer
17.4
Liver Cancer 1026
13.6


(OD06081)


Lung Margin
32.3
Liver Cancer 1025
12.9


(OD06081)


Lung Cancer
4.2
Liver Cancer 6004-T
13.2


(OD04237-01)


Lung Margin
24.7
Liver Tissue 6004-N
1.3


(OD04237-02)


Ocular Melanoma
12.9
Liver Cancer 6005-T
43.2


Metastasis


Ocular Melanoma
10.7
Liver Tissue 6005-N
4.8


Margin (Liver)


Melanoma Metastasis
52.9
Liver Cancer 064003
39.5


Melanoma Margin
21.0
Normal Bladder
9.3


(Lung)


Normal Kidney
4.7
Bladder Cancer 1023
5.8


Kidney Ca, Nuclear
40.3
Bladder Cancer
4.2


grade 2 (OD04338)

A302173


Kidney Margin
7.5
Normal Stomach
31.4


(OD04338)


Kidney Ca Nuclear
82.4
Gastric Cancer
1.2


grade 1/2 (OD04339)

9060397


Kidney Margin
13.2
Stomach Margin
7.1


(OD04339)

9060396


Kidney Ca, Clear cell
8.3
Gastric Cancer
7.4


type (OD04340)

9060395


Kidney Margin
24.7
Stomach Margin
10.9


(OD04340)

9060394


Kidney Ca, Nuclear
13.1
Gastric Cancer 064005
10.4


grade 3 (OD04348)










[1406]

775





TABLE AAE










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3229, Run

Ag3229, Run


Tissue Name
164389704
Tissue Name
164389704













Secondary Th1 act
3.4
HUVEC IL-1beta
20.0


Secondary Th2 act
4.8
HUVEC IFN gamma
32.5


Secondary Tr1 act
2.1
HUVEC TNF alpha +
26.6




IFN gamma


Secondary Th1 rest
1.2
HUVEC TNF alpha +
35.1




IL4


Secondary Th2 rest
2.0
HUVEC IL-11
17.6


Secondary Tr1 rest
4.5
Lung Microvascular EC
34.2




none


Primary Th1 act
17.7
Lung Microvascular EC
49.0




TNF alpha + IL-1beta


Primary Th2 act
5.3
Microvascular Dermal
30.6




EC none


Primary Tr1 act
25.9
Microsvasular Dermal
38.7




EC TNF alpha + IL-1beta


Primary Th1 rest
14.0
Bronchial epithelium
46.7




TNF alpha + IL1beta


Primary Th2 rest
6.5
Small airway epithelium
22.1




none


Primary Tr1 rest
22.1
Small airway epithelium
97.9




TNF alpha + IL-1beta


CD45RA CD4
12.7
Coronery artery SMC rest
31.2


lymphocyte act


CD45RO CD4
6.6
Coronery artery SMC
10.5


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
2.4
Astrocytes rest
7.5


Secondary CD8
4.2
Astrocytes TNF alpha +
8.6


lymphocyte rest

IL-1beta


Secondary CD8
0.0
KU-812 (Basophil) rest
0.8


lymphocyte act


CD4 lymphocyte none
5.6
KU-812 (Basophil)
2.9




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
3.7
CCD1106
6.2


CD95 CH11

(Keratinocytes) none


LAK cells rest
5.9
CCD1106
6.0




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
3.0
Liver cirrhosis
15.5


LAK cells IL-2 + IL-12
6.2
Lupus kidney
12.2


LAK cells IL-2 + IFN
10.7
NCI-H292 none
30.8


gamma


LAK cells IL-2 + IL-18
5.0
NCI-H292 IL-4
49.7


LAK cells
4.0
NCI-H292 IL-9
43.5


PMA/ionomycin


NK Cells IL-2 rest
1.9
NCI-H292 IL-13
31.6


Two Way MLR 3 day
9.0
NCI-H292 IFN gamma
17.7


Two Way MLR 5 day
3.3
HPAEC none
18.0


Two Way MLR 7 day
1.2
HPAEC TNF alpha + IL-
58.2




1beta


PBMC rest
0.8
Lung fibroblast none
40.6


PBMC PWM
10.7
Lung fibroblast TNF
11.0




alpha + IL-1beta


PBMC PHA-L
10.2
Lung fibroblast IL-4
100.0


Ramos (B cell) none
0.0
Lung fibroblast IL-9
55.1


Ramos (B cell)
0.0
Lung fibroblast IL-13
78.5


ionomycin


B lymphocytes PWM
23.3
Lung fibroblast IFN
82.4




gamma


B lymphocytes CD40L
18.6
Dermal fibroblast
45.4


and IL-4

CCD1070 rest


EOL-1 dbcAMP
1.8
Dermal fibroblast
36.3




CCD1070 TNF alpha


EOL-1 dbcAMP
2.0
Dermal fibroblast
23.8


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
5.9
Dermal fibroblast IFN
4.6




gamma


Dendritic cells LPS
8.0
Dermal fibroblast IL-4
16.6


Dendritic cells anti-
3.3
IBD Colitis 2
6.2


CD40


Monocytes rest
4.2
IBD Crohn's
3.6


Monocytes LPS
0.9
Colon
30.1


Macrophages rest
3.1
Lung
19.9


Macrophages LPS
1.4
Thymus
20.6


HUVEC none
35.1
Kidney
20.9


HUVEC starved
58.2










[1407] CNS_neurodegeneration_v1.0 Summary: A3229—This panel confirms the expression of this gene at low levels in the brain in an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.


[1408] General_screening_panel_v1.4 Summary: Ag3229—Highest levels of expression of this gene are seen in breast cancer cell line T47D (CT=28.5). Based on expression in this panel, this gene may be involved in gastric, brain, colon, renal, lung, breast, ovarian and prostate cancer as well as melanomas. Thus, expression of this gene could be used as a diagnostic marker for the presence of these cancers. Furthermore, therapeutic inhibition using antibodies or small molecule drugs might be of use in the treatment of these cancers.


[1409] This gene product is also expressed in adipose, pancreas, adrenal, thyroid, pituitary, skeletal muscle, and heart. This widespread expression in tissues with metabolic function suggests, that this gene product may be important for the pathogenesis, diagnosis, and/or treatment of metabolic and endocrine diseases, including obesity and Types 1 and 2 diabetes.


[1410] In addition, this gene is expressed at low to moderate levels in all regions of the CNS examined. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[1411] Panel 2.2 Summary: Ag3229 Highest expression of the CG57411-01 gene is seen in the kidney (CT=32.2). In addition, significant levels of expression are seen in samples derived from normal lung and breast. Expression in these normal tissues is also higher than in the corresponding malignant tissue. Thus, expression of this gene could be used to differentiate between these samples and other samples on this panel and as a marker to detect the presence of lung, breast and kidney cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of lung, breast and kidney cancer.


[1412] Panel 4D Summary: Ag3229 Highest expression of the CG57411-01 gene is seen in IL-4 treated lung fibroblasts (CT=31.3). Significant levels of expression are seen in activated-NCI-H292 mucoepidermoid cells as well as untreated NCI-H292 cells. Moderate expression is also detected in IL-9, IL-13 and IFN gamma activated lung fibroblasts, human pulmonary aortic endothelial cells (treated and untreated), small airway epithelium (treated and untreated), treated bronchial epithelium and lung microvascular endothelial cells (treated and untreated). The expression of this gene in cells derived from or within the lung suggests that this gene may be involved in normal conditions as well as pathological and inflammatory lung disorders that include chronic obstructive pulmonary disease, asthma, allergy and emphysema. Moderate/low expression of this gene is also detected in treated and untreated HUVECs (endothelial cells) and coronary artery smooth muscle cells (treated and untreated) and normal tissues that include lung, colon, thymus and kidney. Expression in the various immune cell types and tissue samples suggests that therapeutic modulation of this gene product may ameliorate symptoms associated with infectious conditions as well as inflammatory and autoimmune disorders that include psoriasis, allergy, asthma, inflammatory bowel disease, rheumatoid arthritis and osteoarthritis.


[1413] AB. CG57399-01 and CG57399-03: Phospholipase ADRAB-B Precursor


[1414] Expression of gene CG57399-01 and variant CG57399-03 was assessed using the primer-probe sets Ag3952 and Ag3226, described in Tables ABA and ABB. Results of the RTQ-PCR runs are shown in Tables ABC and ABD.
776TABLE ABAProbe Name Ag3952StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-ctgtgtccctgtgtcctgaa-3′201633475ProbeTET-5′-tcaacagaacttgctaccctcatcga-3′-TAMRA261666476Reverse5′-gtgggtcttctcctgaaacttc-3′221701477


[1415]

777





TABLE ABB










Probe Name Ag3226














Start
SEQ ID


Primers
Sequences
Length
Position
NO:














Forward
5′-gatgatcctcaggtcactgtgt-3′
22
1617
478





Probe
TET-5′-ccctgtgtcctgaagtttgatgataactca-3′-TAMRA
30
1639
479





Reverse
5′-tcgatgagggtagcaagttct-3′
21
1671
480










[1416]

778





TABLE ABC










General_screening_panel_v1.4











Rel. Exp. (%) Ag3952, Run

Rel. Exp. (%) Ag3952, Run


Tissue Name
213856126
Tissue Name
213856126













Adipose
9.0
Renal ca. TK-10
15.0


Melanoma*
3.0
Bladder
22.7


Hs688(A).T


Melanoma*
3.4
Gastric ca. (liver met.)
13.0


Hs688(B).T

NCI-N87


Melanoma* M14
0.9
Gastric ca. KATO III
75.3


Melanoma*
11.7
Colon ca. SW-948
4.3


LOXIMVI


Melanoma* SK-
1.5
Colon ca. SW480
97.3


MEL-5


Squamous cell
8.7
Colon ca.* (SW480
4.4


carcinoma SCC-4

met) SW620


Testis Pool
12.8
Colon ca. HT29
0.4


Prostate ca.* (bone
10.5
Colon ca. HCT-116
1.2


met) PC-3


Prostate Pool
12.9
Colon ca. CaCo-2
60.7


Placenta
5.1
Colon cancer tissue
28.7


Uterus Pool
6.5
Colon ca. SW1116
0.0


Ovarian ca.
7.3
Colon ca. Colo-205
0.9


OVCAR-3


Ovarian ca. SK-
26.4
Colon ca. SW-48
26.1


OV-3


Ovarian ca.
1.9
Colon Pool
18.8


OVCAR-4


Ovarian ca.
6.7
Small Intestine Pool
5.3


OVCAR-5


Ovarian ca.
9.2
Stomach Pool
7.9


IGROV-1


Ovarian ca.
4.2
Bone Marrow Pool
8.4


OVCAR-8


Ovary
10.0
Fetal Heart
1.2


Breast ca. MCF-7
0.4
Heart Pool
5.7


Breast ca. MDA-
92.0
Lymph Node Pool
32.1


MB-231


Breast ca. BT 549
5.5
Fetal Skeletal Muscle
1.2


Breast ca. T47D
2.5
Skeletal Muscle Pool
4.7


Breast ca. MDA-N
1.6
Spleen Pool
18.2


Breast Pool
19.6
Thymus Pool
19.3


Trachea
10.3
CNS cancer
38.2




(glio/astro) U87-MG


Lung
1.2
CNS cancer
12.2




(glio/astro) U-118-MG


Fetal Lung
8.3
CNS cancer
0.9




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.9
CNS cancer (astro) SF-
7.6




539


Lung ca. LX-1
27.2
CNS cancer (astro)
17.1




SNB-75


Lung ca. NCI-H146
10.7
CNS cancer (glio)
6.8




SNB-19


Lung ca. SHP-77
47.3
CNS cancer (glio) SF-
5.7




295


Lung ca. A549
5.1
Brain (Amygdala) Pool
7.0


Lung ca. NCI-H526
0.0
Brain (cerebellum)
3.2


Lung ca. NCI-H23
4.1
Brain (fetal)
19.3


Lung ca. NCI-H460
0.5
Brain (Hippocampus)
13.1




Pool


Lung ca. HOP-62
2.7
Cerebral Cortex Pool
14.8


Lung ca. NCI-H522
1.3
Brain (Substantia
6.3




nigra) Pool


Liver
0.0
Brain (Thalamus) Pool
15.2


Fetal Liver
1.7
Brain (whole)
10.4


Liver ca. HepG2
0.5
Spinal Cord Pool
5.3


Kidney Pool
21.2
Adrenal Gland
100.0


Fetal Kidney
1.6
Pituitary gland Pool
4.3


Renal ca. 786-0
1.7
Salivary Gland
3.4


Renal ca. A498
1.3
Thyroid (female)
14.5


Renal ca. ACHN
4.3
Pancreatic ca.
1.7




CAPAN2


Renal ca. UO-31
17.4
Pancreas Pool
24.5










[1417]

779





TABLE ABD










Panel 1.3D











Rel. Exp. (%) Ag3226, Run

Rel. Exp. (%) Ag3226, Run


Tissue Name
167994701
Tissue Name
167994701













Liver adenocarcinoma
2.5
Kidney (fetal)
16.3


Pancreas
0.0
Renal ca. 786-0
0.9


Pancreatic ca. CAPAN2
0.0
Renal ca. A498
1.4


Adrenal gland
19.6
Renal ca. RXF 393
3.4


Thyroid
16.3
Renal ca. ACHN
1.4


Salivary gland
0.0
Renal ca. UO-31
2.8


Pituitary gland
1.9
Renal ca. TK-10
4.4


Brain (fetal)
25.5
Liver
0.0


Brain (whole)
4.6
Liver (fetal)
1.1


Brain (amygdala)
6.7
Liver ca.
0.0




(hepatoblast) HepG2


Brain (cerebellum)
1.6
Lung
8.8


Brain (hippocampus)
22.2
Lung (fetal)
1.7


Brain (substantia nigra)
3.1
Lung ca. (small cell)
18.6




LX-1


Brain (thalamus)
3.2
Lung ca. (small cell)
4.2




NCI-H69


Cerebral Cortex
26.2
Lung ca. (s.cell var.)
100.0




SHP-77


Spinal cord
3.1
Lung ca. (large
0.0




cell)NCI-H460


glio/astro U87-MG
7.5
Lung ca. (non-sm.
6.7




cell) A549


glio/astro U-118-MG
4.2
Lung ca. (non-s.cell)
5.7




NCI-H23


astrocytoma SW1783
1.2
Lung ca. (non-s.cell)
0.0




HOP-62


neuro*; met SK-N-AS
0.0
Lung ca. (non-s.cl)
0.0




NCI-H522


astrocytoma SF-539
0.0
Lung ca. (squam.)
0.9




SW 900


astrocytoma SNB-75
4.3
Lung ca. (squam.)
3.7




NCI-H596


glioma SNB-19
6.0
Mammary gland
6.3


glioma U251
14.1
Breast ca.* (pl.ef)
0.0




MCF-7


glioma SF-295
0.0
Breast ca.* (pl.ef)
45.4




MDA-MB-231


Heart (fetal)
1.4
Breast ca.* (pl.ef)
4.3




T47D


Heart
1.0
Breast ca. BT-549
7.1


Skeletal muscle (fetal)
0.7
Breast ca. MDA-N
0.0


Skeletal muscle
3.2
Ovary
10.9


Bone marrow
3.1
Ovarian ca.
0.0




OVCAR-3


Thymus
5.7
Ovarian ca.
2.4




OVCAR-4


Spleen
7.2
Ovarian ca.
5.2




OVCAR-5


Lymph node
0.0
Ovarian ca.
0.0




OVCAR-8


Colorectal
4.8
Ovarian ca. IGROV-1
0.0


Stomach
5.1
Ovarian ca.*
3.0




(ascites) SK-OV-3


Small intestine
1.5
Uterus
5.8


Colon ca. SW480
33.2
Placenta
0.0


Colon ca.*
8.8
Prostate
1.6


SW620(SW480 met)


Colon ca. HT29
0.0
Prostate ca.* (bone
2.6




met)PC-3


Colon ca. HCT-116
0.0
Testis
7.4


Colon ca. CaCo-2
35.4
Melanoma
0.0




Hs688(A).T


Colon ca.
24.5
Melanoma* (met)
0.0


tissue(ODO3866)

Hs688(B).T


Colon ca. HCC-2998
15.7
Melanoma UACC-
0.0




62


Gastric ca.* (liver met)
6.4
Melanoma M14
0.0


NCI-N87


Bladder
14.6
Melanoma LOX
0.0




IMVI


Trachea
4.4
Melanoma* (met)
0.0




SK-MEL-5


Kidney
2.4
Adipose
17.3










[1418] General_screening_panel_v1.4 Summary: Ag3952 Highest expression of this gene is seen in the adrenal gland (CT=29). Thus, this gene product may be a treatment for Addison's disease and other adrenalopathies. This gene also has low levels of expression in adipose, heart, skeletal muscle, pituitary, thyroid, and pancreas. Therapeutic modulation of this gene product may be important for the diagnosis or treatment of endocrine or metabolic disease, including Types 1 and 2 diabetes, obesity and pancreatitis.


[1419] Expression of this gene is also seen in sample derived from colon, gastric, lung and breast cancers. Thus, expression of this gene could be used to differentiate between these samples and other samples on this panel and as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of colon, gastric, lung and breast cancers.


[1420] Low but significant levels of expression are also seen for all regions of the CNS examined. Thus, this gene product may be useful for treatment of CNS disorders such as Alzheimner's disease, Parkinson's disease, stroke, epilepsy, schizophrenia and multiple sclerosis.


[1421] Panel 1.3D Summary: Ag3952 Highest expression of the CG57399-01 gene is seen in a lung cancer cell line (CT=32.5). Low but significant expression is also seen in cell lines derived from breast and colon cancers. Overall, expression is consistent with expression seen in Panel 1.4. Thus, expression of this gene could be used to differentiate between these samples and other samples on this panel and as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of colon, gastric, lung and breast cancers.


[1422] Among metabolic tissues, significant levels of expression are seen in adipose and the adrenal gland. Thus, this gene product may be useful for treatment of obesity, Addisonl's disease and other adrenalopathies.


[1423] In addition, this gene is expressed in the hippocampus, and cerebral cortex. Both these regions of the brain undergo degeneration in Alzheimer's disease. Thus, therapeutic modulation of the expression or function of this gene may be effective in the treatment of this disease or any other neurodegenerative disorders.


[1424] AC. CG57399-02: Phospholipase Adrab-B Precursor


[1425] Expression of gene CG57399-02 was assessed using the primer-probe set Ag3952, described in Table ACA. Results of the RTQ-PCR runs are shown in Table ACB. Please note that this gene represents a variant of CG57399-01. This sequence however, only corresponds to probe and primer set Ag3952.
780TABLE ACAProbe Name Ag3952SEQ IDPrimersSequencesLengthStart PositionNO:Forward5′-ctgtgtccctgtgtcctgaa-3′20578481ProbeTET-5′-tcaacagaacttgctaccctcatcga-3′-TAMRA26611482Reverse5′-gtgggtcttctcctgaaacttc-3′22646483


[1426]

781





TABLE ACB










General_screening_panel_v1.4











Rel. Exp. (%) Ag3952, Run

Rel. Exp. (%) Ag3952, Run


Tissue Name
213856126
Tissue Name
213856126













Adipose
9.0
Renal ca. TK-10
15.0


Melanoma*
3.0
Bladder
22.7


Hs688(A).T


Melanoma*
3.4
Gastric ca. (liver met.)
13.0


Hs688(B).T

NCI-N87


Melanoma* M14
0.9
Gastric ca. KATO III
75.3


Melanoma*
11.7
Colon ca. SW-948
4.3


LOXIMVI


Melanoma* SK-
1.5
Colon ca. SW480
97.3


MEL-5


Squamous cell
8.7
Colon ca.* (SW480
4.4


carcinoma SCC-4

met) SW620


Testis Pool
12.8
Colon ca. HT29
0.4


Prostate ca.* (bone
10.5
Colon ca. HCT-116
1.2


met) PC-3


Prostate Pool
12.9
Colon ca. CaCo-2
60.7


Placenta
5.1
Colon cancer tissue
28.7


Uterus Pool
6.5
Colon ca. SW1116
0.0


Ovarian ca.
7.3
Colon ca. Colo-205
0.9


OVCAR-3


Ovarian ca. SK-
26.4
Colon ca. SW-48
26.1


OV-3


Ovarian ca.
1.9
Colon Pool
18.8


OVCAR-4


Ovarian ca.
6.7
Small Intestine Pool
5.3


OVCAR-5


Ovarian ca.
9.2
Stomach Pool
7.9


IGROV-1


Ovarian ca.
4.2
Bone Marrow Pool
8.4


OVCAR-8


Ovary
10.0
Fetal Heart
1.2


Breast ca. MCF-7
0.4
Heart Pool
5.7


Breast ca. MDA-
92.0
Lymph Node Pool
32.1


MB-231


Breast ca. BT 549
5.5
Fetal Skeletal Muscle
1.2


Breast ca. T47D
2.5
Skeletal Muscle Pool
4.7


Breast ca. MDA-N
1.6
Spleen Pool
18.2


Breast Pool
19.6
Thymus Pool
19.3


Trachea
10.3
CNS cancer
38.2




(glio/astro) U87-MG


Lung
1.2
CNS cancer
12.2




(glio/astro) U-118-MG


Fetal Lung
8.3
CNS cancer
0.9




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.9
CNS cancer (astro) SF-
7.6




539


Lung ca. LX-1
27.2
CNS cancer (astro)
17.1




SNB-75


Lung ca. NCI-H146
10.7
CNS cancer (glio)
6.8




SNB-19


Lung ca. SHP-77
47.3
CNS cancer (glio) SF-
5.7




295


Lung ca. A549
5.1
Brain (Amygdala) Pool
7.0


Lung ca. NCI-H526
0.0
Brain (cerebellum)
3.2


Lung ca. NCI-H23
4.1
Brain (fetal)
19.3


Lung ca. NCI-H460
0.5
Brain (Hippocampus)
13.1




Pool


Lung ca. HOP-62
2.7
Cerebral Cortex Pool
14.8


Lung ca. NCI-H522
1.3
Brain (Substantia
6.3




nigra) Pool


Liver
0.0
Brain (Thalamus) Pool
15.2


Fetal Liver
1.7
Brain (whole)
10.4


Liver ca. HepG2
0.5
Spinal Cord Pool
5.3


Kidney Pool
21.2
Adrenal Gland
100.0


Fetal Kidney
1.6
Pituitary gland Pool
4.3


Renal ca. 786-0
1.7
Salivary Gland
3.4


Renal ca. A498
1.3
Thyroid (female)
14.5


Renal ca. ACHN
4.3
Pancreatic ca.
1.7




CAPAN2


Renal ca. UO-31
17.4
Pancreas Pool
24.5










[1427] General_screening_panel_v1.4 Summary: Ag3952 Highest expression of this gene is seen in the adrenal gland (CT=29). Thus, this gene product may be a treatment for Addison's disease and other adrenalopathies. This gene also has low levels of expression in adipose., heart, skeletal muscle, pituitary, thyroid, and pancreas. Therapeutic modulation of this gene product may be important for the diagnosis or treatment of endocrine or metabolic disease, including Types 1 and 2 diabetes, obesity and pancreatitis.


[1428] Expression of this gene is also seen in cell line samples derived from colon, gastric, lung and breast cancers. Thus, expression of this gene could be used to differentiate between these samples and other samples on this panel and as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of colon, gastric, lung and breast cancers.


[1429] Low but significant levels of expression are also seen for all regions of the CNS examined. Thus, this gene product may be useful for treatment of CNS disorders such as Alzheimer's disease, Parkinson's disease, stroke, epilepsy, schizophrenia and multiple sclerosis.


[1430] AD. CG59311-01: ACYL-Coenzyme a Thioester Hydrolase bp.


[1431] Expression of gene CG59311-01, splice variant CG59311-02, and full length clone CG59311-03, was assessed using the primer-probe set Ag3541, described in Table ADA. Results of the RTQ-PCR runs are shown in Tables ADB and ADC.


[1432] Table ADA. Probe Name Ag3541
782TABLE ADAProbe Name Ag3541StartSEQ IDPrimerSequencesLengthPositionNO:Forward5′-ctcactcaaaggcacaggtaga-3′221199484ProbeTET-5′-tggcagcaaattcaaactttcttcca-3′-TAMRA261225485Reverse5′-tttgctgtgcttgacagatttt-3′221269486


[1433]

783





TABLE ADB










General_screening_panel_v1.4











Rel. Exp. (%) Ag3541, Run

Rel. Exp. (%) Ag3541, Run


Tissue Name
217049294
Tissue Name
217049294













Adipose
0.0
Renal ca. TK-10
6.0


Melanoma*
0.7
Bladder
3.7


Hs688(A).T


Melanoma*
1.6
Gastric ca. (liver met.)
0.0


Hs688(B).T

NCI-N87


Melanoma* M14
0.0
Gastric ca. KATO III
0.0


Melanoma*
0.0
Colon ca. SW-948
0.0


LOXIMVI


Melanoma* SK-
0.0
Colon ca. SW480
2.7


MEL-5


Squamous cell
0.0
Colon ca.* (SW480
5.4


carcinoma SCC-4

met) SW620


Testis Pool
3.1
Colon ca. HT29
0.0


Prostate ca.* (bone
1.4
Colon ca. HCT-116
0.6


met) PC-3


Prostate Pool
2.3
Colon ca. CaCo-2
0.6


Placenta
0.5
Colon cancer tissue
0.0


Uterus Pool
0.0
Colon ca. SW1116
0.0


Ovarian ca.
2.9
Colon ca. Colo-205
0.0


OVCAR-3


Ovarian ca. SK-
0.0
Colon ca. SW-48
0.0


OV-3


Ovarian ca.
0.9
Colon Pool
4.6


OVCAR-4


Ovarian ca.
27.0
Small Intestine Pool
6.6


OVCAR-5


Ovarian ca.
0.0
Stomach Pool
3.1


IGROV-1


Ovarian ca.
1.8
Bone Marrow Pool
1.4


OVCAR-8


Ovary
2.5
Fetal Heart
9.2


Breast ca. MCF-7
2.4
Heart Pool
3.4


Breast ca. MDA-
8.0
Lymph Node Pool
3.9


MB-231


Breast ca. BT 549
4.9
Fetal Skeletal Muscle
4.9


Breast ca. T47D
52.9
Skeletal Muscle Pool
13.5


Breast ca. MDA-N
0.0
Spleen Pool
0.0


Breast Pool
6.7
Thymus pool
4.7


Trachea
0.9
CNS cancer
0.9




(glio/astro) U87-MG


Lung
1.7
CNS cancer
12.1




(glio/astro) U-118-MG


Fetal Lung
2.2
CNS cancer
0.0




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.0
CNS cancer (astro) SF-
0.0




539


Lung ca. LX-1
4.2
CNS cancer (astro)
5.2




SNB-75


Lung ca. NCI-H146
2.1
CNS cancer (glio)
0.0




SNB-19


Lung ca. SHP-77
6.7
CNS cancer (glio) SF-
0.7




295


Lung ca. A549
0.0
Brain (Amygdala) Pool
4.2


Lung ca. NCI-H526
0.0
Brain (cerebellum)
100.0


Lung ca. NCI-H23
10.2
Brain (fetal)
14.7


Lung ca. NCI-H460
3.4
Brain (Hippocampus)
9.0




Pool


Lung ca. HOP-62
0.0
Cerebral Cortex Pool
9.7


Lung ca. NCI-H522
8.5
Brain (Substantia
3.5




nigra) Pool


Liver
0.5
Brain (Thalamus) Pool
10.5


Fetal Liver
1.5
Brain (whole)
12.9


Liver ca. HepG2
0.5
Spinal Cord Pool
7.6


Kidney Pool
9.8
Adrenal Gland
10.2


Fetal Kidney
7.9
Pituitary gland Pool
3.1


Renal ca. 786-0
0.0
Salivary Gland
1.7


Renal ca. A498
0.0
Thyroid (female)
0.9


Renal ca. ACHN
0.0
Pancreatic ca.
2.8




CAPAN2


Renal ca. UO-31
3.3
Pancreas Pool
6.6










[1434]

784





TABLE ADC










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3541, Run

Ag3541, Run


Tissue Name
166447041
Tissue Name
166447041













Secondary Th1 act
2.7
HUVEC IL-1beta
0.0


Secondary Th2 act
4.1
HUVEC IFN gamma
0.0


Secondary Tr1 act
0.0
HUVEC TNF alpha +
0.0




IFN gamma


Secondary Th1 rest
0.0
HUVEC TNF alpha +
0.0




IL4


Secondary Th2 rest
0.0
HUVEC IL-11
2.1


Secondary Tr1 rest
0.0
Lung Microvascular EC
0.0




none


Primary Th1 act
2.7
Lung Microvascular EC
0.0




TNF alpha + IL-1beta


Primary Th2 act
0.0
Microvascular Dermal
0.0




EC none


Primary Tr1 act
0.0
Microsvasular Dermal
0.0




EC TNF alpha + IL-1beta


Primary Th1 rest
0.0
Bronchial epithelium
0.0




TNF alpha + IL1beta


Primary Th2 rest
0.0
Small airway epithelium
0.0




none


Primary Tr1 rest
0.0
Small airway epithelium
0.0




TNF alpha + IL-1beta


CD45RA CD4
0.0
Coronery artery SMC rest
2.3


lymphocyte act


CD45RO CD4
1.7
Coronery artery SMC
0.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
0.0
Astrocytes rest
1.8


Secondary CD8
0.0
Astrocytes TNF alpha +
0.0


lymphocyte rest

IL-1beta


Secondary CD8
0.0
KU-812 (Basophil) rest
4.2


lymphocyte act


CD4 lymphocyte none
0.0
KU-812 (Basophil)
1.4




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
0.0
CCD1106
0.0


CD95 CH11

(Keratinocytes) none


LAK cells rest
2.8
CCD1106
9.8




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
0.0
Liver cirrhosis
22.2


LAK cells IL-2 + IL-12
0.0
Lupus kidney
18.4


LAK cells IL-2 + IFN
0.0
NCI-H292 none
10.4


gamma


LAK cells IL-2 + IL-18
0.0
NCI-H292 IL-4
7.2


LAK cells
0.0
NCI-H292 IL-9
15.2


PMA/ionomycin


NK Cells IL-2 rest
1.7
NCI-H292 IL-13
3.1


Two Way MLR 3 day
0.0
NCI-H292 IFN gamma
7.3


Two Way MLR 5 day
5.3
HPAEC none
0.0


Two Way MLR 7 day
0.0
HPAEC TNF alpha + IL-
0.0




1beta


PBMC rest
0.0
Lung fibroblast none
1.7


PBMC PWM
0.0
Lung fibroblast TNF
5.7




alpha + IL-1beta


PBMC PHA-L
2.0
Lung fibroblast IL-4
0.0


Ramos (B cell) none
0.0
Lung fibroblast IL-9
0.0


Ramos (B cell)
2.2
Lung fibroblast IL-13
3.2


ionomycin


B lymphocytes PWM
0.0
Lung fibroblast IFN
0.0




gamma


B lymphocytes CD40L
0.0
Dermal fibroblast
2.9


and IL-4

CCD1070 rest


EOL-1 dbcAMP
0.0
Dermal fibroblast
2.9




CCD1070 TNF alpha


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
0.0
Dermal fibroblast IFN
0.0




gamma


Dendritic cells LPS
3.5
Dermal fibroblast IL-4
1.5


Dendritic cells anti-
0.0
IBD Colitis 2
5.4


CD40


Monocytes rest
0.0
IBD Crohn's
0.0


Monocytes LPS
0.0
Colon
14.1


Macrophages rest
4.5
Lung
0.0


Macrophages LPS
2.1
Thymus
100.0


HUVEC none
0.0
Kidney
2.3


HUVEC starved
2.5










[1435] CNS_neurodegeneration_v1.0 Summary: Ag3541—Expression of this gene is low/undetectable (CTs>34.5) across all of the samples on this panel (data not shown).


[1436] General_screening_panel_v1.4 Summary: Ag3541 Significant expression of this gene is seen only in cerebellum, fetal brain, the breast cancer cell line T47D, and ovarian cancer cell line OVCAR-5 (CTs=32-35). Therefore, expression of this gene can be used to differentiate between these samples and others on this panel.


[1437] Panel 4D Summary: Ag3541—There is significant expression of this gene only in thymus (CT=33.8). Therefore, expression of this gene may be used to identify thymic tissue. Furthermore, drugs that inhibit the function of this protein may regulate T cell development in the thymus and reduce or eliminate the symptoms of T cell mediated autoimmune or inflammatory diseases, including asthma, allergies, inflammatory bowel disease, lupus erythematosus, or rheumatoid arthritis. Additionally, therapeutics designed against this putative protein may disrupt T cell development in the thymus and function as an immunosuppresant for tissue transplant.


[1438] AE. CG59309-01: Acyl-Coenzyme a Thioester Hydrolase


[1439] Expression of gene CG59309-01 was assessed using the primer-probe set Ag3540, described in Table AEA. Results of the RTQ-PCR runs are shown in Tables AEB, AEC, AED and AEE.


[1440] Table AEA. Probe Name Ag3540
785TABLE AEAProbe Name Ag3540StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-ccacgttggctctagcttatta-3′22649487ProbeTET-5′-tgaagatctccccaataacatggaca-3′-TAMRA26677488Reverse5′-ttcgaagtactccagggatatg-3′22704489


[1441]

786





TABLE AEB










CNS_neurodegeneration_v1.0











Rel. Exp. (%) Ag3540,

Rel. Exp. (%) Ag3540,


Tissue Name
Run 210638385
Tissue Name
Run 210638385













AD 1 Hippo
13.7
Control (Path) 3
8.2




Temporal Ctx


AD 2 Hippo
26.2
Control (Path) 4
34.2




Temporal Ctx


AD 3 Hippo
13.1
AD 1 Occipital
23.2




Ctx


AD 4 Hippo
3.4
AD 2 Occipital
0.0




Ctx (Missing)


AD 5 hippo
30.4
AD 3 Occipital
7.8




Ctx


AD 6 Hippo
55.9
AD 4 Occipital
15.0




Ctx


Control 2 Hippo
24.0
AD 5 Occipital
8.1




Ctx


Control 4 Hippo
4.5
AD 6 Occipital
76.3




Ctx


Control (Path) 3
6.2
Control 1 Occipital
3.6


Hippo

Ctx


AD 1 Temporal Ctx
11.0
Control 2 Occipital
96.6




Ctx


AD 2 Temporal Ctx
19.5
Control 3 Occipital
36.3




Ctx


AD 3 Temporal Ctx
4.8
Control 4 Occipital
3.9




Ctx


AD 4 Temporal Ctx
15.6
Control (Path) 1
100.0




Occipital Ctx


AD 5 Inf Temporal
36.9
Control (Path) 2
7.6


Ctx

Occipital Ctx


AD 5 SupTemporal
27.4
Control (Path) 3
1.6


Ctx

Occipital Ctx


AD 6 Inf Temporal
47.3
Control (Path) 4
16.6


Ctx

Occipital Ctx


AD 6 Sup Temporal
64.2
Control 1 Parietal
8.7


Ctx

Ctx


Control 1 Temporal
7.0
Control 2 Parietal
20.7


Ctx

Ctx


Control 2 Temporal
53.2
Control 3 Parietal
27.2


Ctx

Ctx


Control 3 Temporal
19.9
Control (Path) 1
88.9


Ctx

Parietal Ctx


Control 4 Temporal
10.5
Control (Path) 2
10.8


Ctx

Parietal Ctx


Control (Path) 1
68.3
Control (Path) 3
10.1


Temporal Ctx

Parietal Ctx


Control (Path) 2
25.3
Control (Path) 4
47.6


Temporal Ctx

Parietal Ctx










[1442]

787





TABLE AEC










General_screening_panel_v1.4











Rel. Exp. (%) Ag3540, Run

Rel. Exp. (%) Ag3540, Run


Tissue Name
217049291
Tissue Name
217049291













Adipose
1.3
Renal ca. TK-10
0.1


Melanoma*
0.7
Bladder
1.1


Hs688(A).T


Melanoma*
0.5
Gastric ca. (liver met.)
5.6


Hs688(B).T

NCI-N87


Melanoma* M14
0.2
Gastric ca. KATO III
0.0


Melanoma*
0.0
Colon ca. SW-948
0.0


LOXIMVI


Melanoma* SK-
0.0
Colon ca. SW480
10.3


MEL-5


Squamous cell
0.3
Colon ca.* (SW480
2.8


carcinoma SCC-4

met) SW620


Testis Pool
0.3
Colon ca. HT29
0.8


Prostate ca.* (bone
0.8
Colon ca. HCT-116
0.0


met) PC-3


Prostate Pool
0.3
Colon ca. CaCo-2
3.5


Placenta
1.4
Colon cancer tissue
1.4


Uterus Pool
0.1
Colon ca. SW1116
0.0


Ovarian ca.
1.6
Colon ca. Colo-205
3.3


OVCAR-3


Ovarian ca. SK-
3.6
Colon ca. SW-48
1.7


OV-3


Ovarian ca.
0.4
Colon Pool
0.2


OVCAR-4


Ovarian ca.
23.7
Small Intestine Pool
0.3


OVCAR-5


Ovarian ca.
0.0
Stomach Pool
0.1


IGROV-1


Ovarian ca.
0.0
Bone Marrow Pool
0.2


OVCAR-8


Ovary
0.1
Fetal Heart
0.4


Breast ca. MCF-7
0.0
Heart Pool
0.2


Breast ca. MDA-
2.5
Lymph Node Pool
0.3


MB-231


Breast ca. BT 549
3.0
Fetal Skeletal Muscle
0.1


Breast ca. T47D
100.0
Skeletal Muscle Pool
0.4


Breast ca. MDA-N
0.0
Spleen Pool
0.2


Breast Pool
0.3
Thymus Pool
0.3


Trachea
0.4
CNS cancer
0.0




(glio/astro) U87-MG


Lung
0.0
CNS cancer
0.3




(glio/astro) U-118-MG


Fetal Lung
0.2
CNS cancer
1.0




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.0
CNS cancer (astro) SF-
0.6




539


Lung ca. LX-1
3.5
CNS cancer (astro)
3.1




SNB-75


Lung ca. NCI-H146
0.0
CNS cancer (glio)
0.0




SNB-19


Lung ca. SHP-77
0.1
CNS cancer (glio) SF-
0.2




295


Lung ca. A549
1.4
Brain (Amygdala) Pool
0.7


Lung ca. NCI-H526
0.7
Brain (cerebellum)
2.1


Lung ca. NCI-H23
1.3
Brain (fetal)
0.5


Lung ca. NCI-H460
0.8
Brain (Hippocampus)
1.0




Pool


Lung ca. HOP-62
1.2
Cerebral Cortex Pool
0.9


Lung ca. NCI-H522
0.0
Brain (Substantia
1.3




nigra) Pool


Liver
2.6
Brain (Thalamus) Pool
1.1


Fetal Liver
0.8
Brain (whole)
1.4


Liver ca. HepG2
0.1
Spinal Cord Pool
0.5


Kidney Pool
0.7
Adrenal Gland
0.8


Fetal Kidney
0.6
Pituitary gland Pool
0.1


Renal ca. 786-0
0.0
Salivary Gland
0.2


Renal ca. A498
0.0
Thyroid (female)
0.7


Renal ca. ACHN
0.0
Pancreatic ca.
9.4




CAPAN2


Renal ca. UO-31
1.1
Pancreas Pool
0.9










[1443]

788





TABLE AED










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3540, Run

Ag3540, Run


Tissue Name
166447040
Tissue Name
166447040













Secondary Th1 act
4.8
HUVEC IL-1beta
1.7


Secondary Th2 act
10.2
HUVEC IFN gamma
0.9


Secondary Tr1 act
12.9
HUVEC TNF alpha +
1.5




IFN gamma


Secondary Th1 rest
2.1
HUVEC TNF alpha +
0.8




IL4


Secondary Th2 rest
1.4
HUVEC IL-11
1.5


Secondary Tr1 rest
1.6
Lung Microvascular EC
0.6




none


Primary Th1 act
4.7
Lung Microvascular EC
0.8




TNF alpha + IL-1beta


Primary Th2 act
6.8
Microvascular Dermal
1.5




EC none


Primary Tr1 act
7.3
Microsvasular Dermal
0.8




EC TNF alpha + IL-1beta


Primary Th1 rest
6.6
Bronchial epithelium
1.3


7

TNF alpha + IL1beta


Primary Th2 rest
2.6
Small airway epithelium
0.6




none


Primary Tr1 rest
4.2
Small airway epithelium
0.0




TNF alpha + IL-1beta


CD45RA CD4
4.1
Coronery artery SMC rest
0.9


lymphocyte act


CD45RO CD4
10.9
Coronery artery SMC
0.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
6.6
Astrocytes rest
2.6


Secondary CD8
17.0
Astrocytes TNF alpha +
2.1


lymphocyte rest

IL-1beta


Secondary CD8
6.0
KU-812 (Basophil) rest
2.2


lymphocyte act


CD4 lymphocyte none
2.0
KU-812 (Basophil)
10.2




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
2.4
CCD1106
6.8


CD95 CH11

(Keratinocytes) none


LAK cells rest
2.0
CCD1106
25.7




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
16.2
Liver cirrhosis
12.0


LAK cells IL-2 + IL-12
12.8
Lupus kidney
5.1


LAK cells IL-2 + IFN
15.6
NCI-H292 none
44.8


gamma


LAK cells IL-2 + IL-18
7.4
NCI-H292 IL-4
37.6


LAK cells
3.4
NCI-H292 IL-9
41.2


PMA/ionomycin


NK Cells IL-2 rest
9.0
NCI-H292 IL-13
19.8


Two Way MLR 3 day
10.5
NCI-H292 IFN gamma
30.1


Two Way MLR 5 day
7.2
HPAEC none
1.2


Two Way MLR 7 day
8.9
HPAEC TNF alpha + IL-
3.3




1beta


PBMC rest
0.5
Lung fibroblast none
0.9


PBMC PWM
3.8
Lung fibroblast TNF
0.7




alpha + IL-1beta


PBMC PHA-L
1.0
Lung fibroblast IL-4
0.5


Ramos (B cell) none
0.0
Lung fibroblast IL-9
0.0


Ramos (B cell)
0.0
Lung fibroblast IL-13
0.9


ionomycin


B lymphocytes PWM
10.3
Lung fibroblast IFN
1.2




gamma


B lymphocytes CD40L
3.8
Dermal fibroblast
1.1


and IL-4

CCD1070 rest


EOL-1 dbcAMP
0.0
Dermal fibroblast
18.9




CCD1070 TNF alpha


EOL-1 dbcAMP
0.0
Dermal fibroblast
1.9


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
14.9
Dermal fibroblast IFN
0.0




gamma


Dendritic cells LPS
8.9
Dermal fibroblast IL-4
1.5


Dendritic cells anti-
7.9
IBD Colitis 2
2.9


CD40


Monocytes rest
0.0
IBD Crohn's
1.9


Monocytes LPS
0.6
Colon
82.9


Macrophages rest
40.3
Lung
9.7


Macrophages LPS
6.1
Thymus
100.0


HUVEC none
1.1
Kidney
1.8


HUVEC starved
1.4










[1444]

789





TABLE AEE










Panel 5 Islet











Rel. Exp. (%)

Rel. Exp. (%)



Ag3540, Run

Ag3540, Run


Tissue Name
242386396
Tissue Name
242386396













97457_Patient-
3.3
94709_Donor 2 AM - A_adipose
9.1


02go_adipose


97476_Patient-
0.8
94710_Donor 2 AM - B_adipose
1.6


07sk_skeletal muscle


97477_Patient-
0.0
94711_Donor 2 AM - C_adipose
1.4


07ut_uterus


97478_Patient-
12.9
94712_Donor 2 AD - A_adipose
2.8


07pl_placenta


99167_Bayer Patient 1
15.5
94713_Donor 2 AD - B_adipose
5.8


97482_Patient-
3.4
94714_Donor 2 AD - C_adipose
4.2


08ut_uterus


97483_Patient-
3.4
94742_Donor 3 U -
3.0


08pl_placenta

A_Mesenchymal Stem Cells


97486_Patient-
100.0
94743_Donor 3 U -
1.1


09sk_skeletal muscle

B_Mesenchymal Stem Cells


97487_Patient-
1.6
94730_Donor 3 AM - A_adipose
4.3


09ut_uterus


97488_Patient-
2.6
94731_Donor 3 AM - B_adipose
2.0


09pl_placenta


97492_Patient-
3.1
94732_Donor 3 AM - C_adipose
2.0


10ut_uterus


97493_Patient-
23.2
94733_Donor 3 AD - A_adipose
10.7


10pl_placenta


97495_Patient-
0.8
94734_Donor 3 AD - B_adipose
3.0


11go_adipose


97496_Patient-
0.0
94735_Donor 3 AD - C_adipose
4.0


11sk_skeletal muscle


97497_Patient-
2.5
77138_Liver_HepG2untreated
0.7


11ut_uterus


97498_Patient-
6.7
73556_Heart_Cardiac stromal
0.0


11pl_placenta

cells (primary)


97500_Patient-
6.5
81735_Small Intestine
4.8


12go_adipose


97501_Patient-
4.5
72409_Kidney_Proximal
0.7


12sk_skeletal muscle

Convoluted Tubule


97502_Patient-
6.7
82685_Small
3.6


12ut_uterus

intestine_Duodenum


97503_Patient-
2.4
90650_Adrenal_Adrenocortical
0.6


12pl_placenta

adenoma


94721_Donor 2 U -
2.2
72410_Kidney_HRCE
8.0


A_Mesenchymal


Stem Cells


94722_Donor 2 U -
0.6
72411_Kidney_HRE
8.5


B_Mesenchymal


Stem Cells


94723_Donor 2 U -
3.1
73139_Uterus_Uterine smooth
0.0


C_Mesenchymal

muscle cells


Stem Cells










[1445] CNS_neurodegeneration_v1.0 Summary: Ag3540—This panel confirms the expression of this gene at low levels in the brain in an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment.


[1446] General_screening_panel_v1.4 Summary: Ag3540 This gene is most highly expressed in a breast cancer cell line (CT=27.1). Thus, expression of this gene could be used to differentiate between this sample and other samples on this panel and as a marker to detect the presence of breast cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of breast cancer.


[1447] Among metabolic tissues, this gene, an acyl coA thioesterase homolog, has a low level of expression in adipose, adult and fetal liver, adrenal, thyroid and pancreas. Acyl CoA thioesterases have multiple roles in lipid homeostasis. Therefore, therapeutic modulation of this gene product may be a treatment for endocrine and metabolic disease, including Types 1 and 2 diabetes and obesity.


[1448] In addition, this gene is expressed in all CNS regions examined. Thus, therapeutic modulation of the expression or function of this gene may be effective in the treatment of neurologic disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, stroke, schizophrenia and multiple sclerosis.



REFERENCES

[1449] 1. Hunt M C, Alexson S E. The role Acyl-CoA thioesterases play in mediating intracellular lipid metabolism. Prog Lipid Res. March 2002;41(2):99-130.


[1450] 2. Hunt M C, Nousiainen S E, Huttunen M K, Orii K E, Svensson L T, Alexson S E. Peroxisome proliferator-induced long chain acyl-CoA thioesterases comprise a highly conserved novel multi-gene family involved in lipid metabolism. J. Biol. Chem. Nov. 26, 1999;274(48):34317-26.


[1451] Panel 4D Summary: Ag3540 Highest expression of the CG59309-01 gene is seen in the thymus and colon (CTs=31.5). Significant levels of expression are also seen in a cluter of treated and untreated samples derived from the NCI-H292 mucoepidermoid cell line. Thus, expression of this gene could be used as a marker for thymus and colon. Furthermore, therapeutic modulation of the expression or function of this gene may regulate T cell development in the thymus and reduce or eliminate the symptoms of T cell mediated autoimmune or inflammatory diseases, including asthma, allergies, inflammatory bowel disease, lupus erythematosus, or rheumatoid arthritis. Additionally, small molecule or antibody therapeutics designed against this putative protein may disrupt T cell development in the thymus and function as an immunosuppresant for tissue transplant.


[1452] Panel 5 Islet Summary: Ag3540 This gene has moderate expression in skeletal muscle, (highest expression CT=30.5). Acyl CoA thioesterases function in peroxisomal fatty acid oxidation. Therefore, therapeutic modulation of this homolog may increase fatty acid oxidation in muscle and be a treatment for Type 2 diabetes and obesity.


[1453] REFERENCES


[1454] 1. Hunt M C, Solaas K, Kase B F, Alexson S E. Characterization of an acyl-coA thioesteirase that functions as a major regulator of peroxisomal lipid metabolism. J. Biol. Chem. Jan. 11, 2002;277(2):1128-38.


[1455] AF. CG57364-01: CG6896


[1456] Expression of gene CG57364-01 was assessed using the primer-probe sets Ag3218 and Ag3378, described in Tables AFA and AFB. Results of the RTQ-PCR runs are shown in Tables AFC, AFD, AFE and AFF.


[1457] Table AFA. Probe Name Ag3218
790TABLE AFAProbe Name Ag3218StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-ctcctgaagcaggtcctctt-3′20249490ProbeTET-5′-cctcccagtgttgtccttctggagg-3′-TAMRA25270491Reverse5′-gacttcttccaggtcatttcg-3′21303492


[1458] Table AFB. Probe Name Ag3378
791TABLE AFBProbe Name Ag3378StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-ctcctgaagcaggtcctctt-3′20249493ProbeTET-5′-cctcccagtgttgtccttctggagg-3′-TAMRA25270494Reverse5′-gacttcttccaggtcatttcg-3′21303495


[1459]

792





TABLE AFC










CNS_neurodegeneration_v1.z0













Rel. Exp. (%)
Rel. Exp. (%)

Rel. Exp. (%)
Rel. Exp. (%)



Ag3218, Run
Ag3378, Run
Tissue
Ag3218, Run
Ag3378, Run


Tissue Name
209861784
210154573
Name
209861784
210154573















AD 1 Hippo
37.6
30.4
Control
17.6
16.7





(Path) 3





Temporal





Ctx


AD 2 Hippo
31.0
37.6
Control
37.6
31.2





(Path) 4





Temporal





Ctx


AD 3 Hippo
34.2
21.5
AD 1
56.3
40.3





Occipital





Ctx


AD 4 Hippo
40.6
25.3
AD 2
0.0
0.0





Occipital





Ctx





(Missing)


AD 5 hippo
100.0
69.3
AD 3
43.2
24.1





Occipital





Ctx


AD 6 Hippo
62.9
55.9
AD 4
80.1
24.3





Occipital





Ctx


Control 2
55.1
52.9
AD 5
17.9
25.2


Hippo


Occipital





Ctx


Control 4
35.4
39.5
AD 6
66.9
55.5


Hippo


Occipital





Ctx


Control (Path)
22.8
26.8
Control 1
27.9
17.4


3 Hippo


Occipital





Ctx


AD 1 Temporal
40.3
28.3
Control 2
94.0
64.6


Ctx


Occipital





Ctx


AD 2 Temporal
83.5
94.6
Control 3
43.5
40.6


Ctx


Occipital





Ctx


AD 3 Temporal
30.8
24.5
Control 4
20.3
22.5


Ctx


Occipital





Ctx


AD 4 Temporal
61.1
26.8
Control
79.6
51.4


Ctx


(Path) 1





Occipital





Ctx


AD 5 Inf
84.7
100.0
Control
34.4
24.7


Temporal Ctx


(Path) 2





Occipital





Ctx


AD 5
55.9
39.8
Control
25.2
16.2


SupTemporal


(Path) 3


Ctx


Occipital





Ctx


AD 6 Inf
47.0
46.0
Control
76.3
45.1


Temporal Ctx


(Path) 4





Occipital





Ctx


AD 6 Sup
63.7
41.2
Control 1
31.0
21.9


Temporal Ctx


Parietal Ctx


Control 1
32.8
18.0
Control 2
67.4
45.1


Temporal Ctx


Parietal Ctx


Control 2
52.1
39.2
Control 3
31.4
29.3


Temporal Ctx


Parietal Ctx


Control 3
34.9
28.1
Control
48.6
58.6


Temporal Ctx


(Path) 1





Parietal Ctx


Control 4
62.9
36.3
Control
46.3
27.0


Temporal Ctx


(Path) 2





Parietal Ctx


Control (Path)
75.8
50.0
Control
26.1
23.8


1 Temporal Ctx


(Path) 3





Parietal Ctx


Control (Path)
56.6
41.8
Control
48.0
54.3


2 Temporal Ctx


(Path) 4





Parietal Ctx










[1460]

793





TABLE AFD










Panel 1.3D













Rel.
Rel.

Rel.
Rel.



Exp. (%)
Exp. (%)

Exp. (%)
Exp. (%)



Ag3218,
Ag3378,

Ag3218,
Ag3378,



Run
Run

Run
Run


Tissue Name
168013878
165674263
Tissue Name
168013878
165674263















Liver
10.7
20.2
Kidney (fetal)
48.3
13.9


adenocarcinoma


Pancreas
10.8
13.1
Renal ca. 786-0
15.6
10.4


Pancreatic ca.
9.6
5.4
Renal ca.
19.2
14.9


CAPAN 2


A498


Adrenal gland
5.1
18.4
Renal ca. RXF
39.0
33.2





393


Thyroid
12.3
33.2
Renal ca.
12.1
11.3





ACHN


Salivary gland
5.1
5.5
Renal ca. UO-
18.9
17.8





31


Pituitary gland
21.5
74.7
Renal ca. TK-
20.0
10.1





10


Brain (fetal)
19.5
36.1
Liver
18.0
8.7


Brain (whole)
22.1
29.9
Liver (fetal)
5.5
25.3


Brain (amygdala)
57.4
46.7
Liver ca.
14.2
14.1





(hepatoblast)





HepG2


Brain (cerebellum)
25.2
23.5
Lung
14.1
18.7


Brain
28.1
85.9
Lung (fetal)
17.2
4.0


(hippocampus)


Brain (substantia
11.5
16.7
Lung ca.
6.5
14.8


nigra)


(small cell)





LX-1


Brain (thalamus)
57.0
67.4
Lung ca.
20.6
4.8





(small cell)





NCI-H69


Cerebral Cortex
75.8
36.9
Lung ca.
100.0
39.8





(s.cell var.)





SHP-77


Spinal cord
9.7
13.2
Lung ca.
5.0
37.1





(large





cell)NCI-





H460


glio/astro U87-
22.8
13.6
Lung ca. (non-
27.7
13.6


MG


sm. cell) A549


glio/astro U-118-
37.4
79.6
Lung ca. (non-
61.1
44.1


MG


s.cell) NCI-





H23


astrocytoma
29.9
14.9
Lung ca. (non-
29.9
13.7


SW1783


s.cell) HOP-





62


neuro*; met SK-
17.1
52.5
Lung ca. (non-
11.3
3.1


N-AS


s.cl) NCI-





H522


astrocytoma SF-
15.5
16.0
Lung ca.
23.2
13.5


539


(squam.) SW





900


astrocytoma SNB-
43.8
50.0
Lung ca.
41.5
10.2


75


(squam.) NCI-





H596


glioma SNB-19
17.9
26.2
Mammary
14.8
35.1





gland


glioma U251
47.6
39.0
Breast ca.*
48.6
39.0





(pl.ef) MCF-7


glioma SF-295
12.3
10.7
Breast ca.*
25.9
60.7





(pl.ef) MDA-





MB-231


Heart (fetal)
38.4
8.0
Breast ca.*
77.4
21.2





(pl.ef) T47D


Heart
3.5
5.0
Breast ca. BT-
47.0
95.9





549


Skeletal muscle
17.0
10.0
Breast ca.
16.6
7.3


(fetal)


MDA-N


Skeletal muscle
4.4
7.2
Ovary
10.1
4.7


Bone marrow
1.3
14.7
Ovarian ca.
36.3
31.2





OVCAR-3


Thymus
13.9
12.3
Ovarian ca.
33.0
20.7





OVCAR-4


Spleen
2.6
12.9
Ovarian ca.
42.6
15.7





OVCAR-5


Lymph node
1.7
15.9
Ovarian ca.
8.7
5.2





OVCAR-8


Colorectal
18.2
11.8
Ovarian ca.
11.3
15.1





IGROV-1


Stomach
14.8
33.7
Ovarian ca.*
43.5
17.0





(ascites) SK-





OV-3


Small intestine
18.3
66.0
Uterus
10.5
21.8


Colon ca. SW480
12.9
14.2
Placenta
2.6
15.0


Colon ca.*
17.0
14.2
Prostate
11.7
30.6


SW620 (SW480


met)


Colon ca. HT29
17.2
18.8
Prostate ca.*
35.4
40.3





(bone met) PC-3


Colon ca. HCT-
16.5
18.2
Testis
23.3
100.0


116


Colon ca. CaCo-2
20.9
7.4
Melanoma
5.0
1.4





Hs688(A).T


Colon ca.
14.7
21.9
Melanoma*
6.0
3.5


tissue (ODO3866)


(met)





Hs688(B).T


Colon ca. HCC-
22.1
13.1
Melanoma
14.3
12.2


2998


UACC-62


Gastric ca.* (liver
48.6
82.4
Melanoma
3.1
8.2


met) NCI-N87


M14


Bladder
6.2
4.7
Melanoma
30.1
8.4





LOX IMVI


Trachea
12.8
49.3
Melanoma*
21.8
13.1





(met) SK-





MEL-5


Kidney
43.5
35.4
Adipose
9.2
3.0










[1461]

794





TABLE AFE










Panel 2.2











Rel. Exp. (%)

Rel. Exp. (%)



Ag3218, Run

Ag3218, Run


Tissue Name
174416494
Tissue Name
174416494













Normal Colon
5.9
Kidney Margin
70.2




(OD04348)


Colon cancer
5.6
Kidney malignant
3.9


(OD06064)

cancer (OD06204B)


Colon Margin
3.6
Kidney normal
6.7


(OD06064)

adjacent tissue




(OD06204E)


Colon cancer
6.3
Kidney Cancer
15.1


(OD06159)

(OD04450-01)


Colon Margin
7.0
Kidney Margin
3.1


(OD06159)

(OD04450-03)


Colon cancer
2.6
Kidney Cancer
2.5


(OD06297-04)

8120613


Colon Margin
5.6
Kidney Margin
18.2


(OD06297-05)

8120614


CC Gr.2 ascend colon
20.0
Kidney Cancer
2.4


(ODO3921)

9010320


CC Margin (ODO3921)
13.7
Kidney Margin
4.4




9010321


Colon cancer metastasis
0.0
Kidney Cancer
23.0


(OD06104)

8120607


Lung Margin
11.0
Kidney Margin
15.1


(OD06104)

8120608


Colon mets to lung
29.9
Normal Uterus
2.3


(OD04451-01)


Lung Margin
0.3
Uterine Cancer 064011
6.1


(OD04451-02)


Normal Prostate
5.6
Normal Thyroid
6.6


Prostate Cancer
3.9
Thyroid Cancer
6.8


(OD04410)

064010


Prostate Margin
6.1
Thyroid Cancer
11.9


(OD04410)

A302152


Normal Ovary
7.0
Thyroid Margin
7.7




A302153


Ovarian cancer
1.3
Normal Breast
3.4


(OD06283-03)


Ovarian Margin
0.0
Breast Cancer
9.9


(OD06283-07)

(OD04566)


Ovarian Cancer 064008
31.2
Breast Cancer 1024
16.8


Ovarian cancer
3.5
Breast Cancer
100.0


(OD06145)

(OD04590-01)


Ovarian Margin
8.4
Breast Cancer Mets
26.2


(OD06145)

(OD04590-03)


Ovarian cancer
13.7
Breast Cancer
36.3


(OD06455-03)

Metastasis (OD04655-




05)


Ovarian Margin
1.1
Breast Cancer 064006
5.4


(OD06455-07)


Normal Lung
5.4
Breast Cancer 9100266
12.8


Invasive poor diff. lung
14.5
Breast Margin
1.0


adeno (ODO4945-01)

9100265


Lung Margin
2.7
Breast Cancer
3.3


(ODO4945-03)

A209073


Lung Malignant Cancer
1.8
Breast Margin
11.7


(OD03126)

A2090734


Lung Margin
5.1
Breast cancer
6.9


(OD03126)

(OD06083)


Lung Cancer
12.8
Breast cancer node
10.7


(OD05014A)

metastasis (OD06083)


Lung Margin
3.3
Normal Liver
9.4


(OD05014B)


Lung cancer
6.3
Liver Cancer 1026
2.6


(OD06081)


Lung Margin
2.7
Liver Cancer 1025
9.7


(OD06081)


Lung Cancer
12.9
Liver Cancer 6004-T
10.4


(OD04237-01)


Lung Margin
6.4
Liver Tissue 6004-N
5.3


(OD04237-02)


Ocular Melanoma
4.6
Liver Cancer 6005-T
4.2


Metastasis


Ocular Melanoma
0.1
Liver Tissue 6005-N
11.5


Margin (Liver)


Melanoma Metastasis
1.6
Liver Cancer 064003
22.5


Melanoma Margin
4.6
Normal Bladder
6.1


(Lung)


Normal Kidney
10.4
Bladder Cancer 1023
10.8


Kidney Ca, Nuclear
14.6
Bladder Cancer
15.1


grade 2 (OD04338)

A302173


Kidney Margin
10.5
Normal Stomach
15.0


(OD04338)


Kidney Ca Nuclear
44.8
Gastric Cancer
7.1


grade 1/2 (OD04339)

9060397


Kidney Margin
17.7
Stomach Margin
10.4


(OD04339)

9060396


Kidney Ca, Clear cell
5.3
Gastric Cancer
8.4


type (OD04340)

9060395


Kidney Margin
25.3
Stomach Margin
10.4


(OD04340)

9060394


Kidney Ca, Nuclear
7.5
Gastric Cancer 064005
7.7


grade 3 (OD04348)










[1462]

795





TABLE AFF










Panel 4D













Rel.
Rel.

Rel.
Rel.



Exp. (%)
Exp. (%)

Exp. (%)
Exp. (%)



Ag3218,
Ag3378,

Ag3218,
Ag3378,



Run
Run

Run
Run


Tissue Name
164682519
165296553
Tissue Name
164682519
165296553















Secondary Th1 act
18.2
25.7
HUVEC IL-1beta
14.5
12.9


Secondary Th2 act
39.0
26.6
HUVEC IFN
47.0
25.3





gamma


Secondary Tr1 act
33.2
19.1
HUVEC TNF
43.5
45.1





alpha + IFN





gamma


Secondary Th1 rest
9.5
12.2
HUVEC TNF
37.1
48.0





alpha + IL4


Secondary Th2 rest
11.2
5.1
HUVEC IL-11
43.5
18.0


Secondary Tr1 rest
22.7
8.0
Lung
16.8
61.6





Microvascular EC





none


Primary Th1 act
43.2
27.9
Lung
18.6
14.7





Microvascular EC





TNF alpha + IL-





1beta


Primary Th2 act
30.1
12.0
Microvascular
31.2
23.8





Dermal EC none


Primary Tr1 act
24.7
14.4
Microsvasular
66.4
22.1





Dermal EC





TNF alpha + IL-





1beta


Primary Th1 rest
25.2
17.4
Bronchial
30.6
29.3





epithelium





TNF alpha +





IL-1beta


Primary Th2 rest
15.5
7.5
Small airway
36.1
24.3





epithelium none


Primary Tr1 rest
21.3
6.7
Small airway
76.3
62.9





epithelium





TNF alpha + IL-





1beta


CD45RA CD4
35.4
16.6
Coronery artery
49.7
28.1


lymphocyte act


SMC rest


CD45RO CD4
27.9
25.9
Coronery artery
25.3
23.7


lymphocyte act


SMC TNF





alpha + IL-1beta


CD8 lymphocyte
21.0
14.8
Astrocytes rest
22.2
31.2


act


Secondary CD8
39.2
17.8
Astrocytes
26.1
25.0


lymphocyte rest


TNF alpha + IL-





1beta


Secondary CD8
20.9
7.4
KU-812
90.8
85.3


lymphocyte act


(Basophil) rest


CD4 lymphocyte
4.5
11.8
KU-812
87.1
72.2


none


(Basophil)





PMA/ionomycin


2ry
2.6
10.0
CCD1106
36.6
36.9


Th1/Th2/Tr1_anti-


(Keratinocytes)


CD95 CH11


none


LAK cells rest
11.7
12.3
CCD1106
33.4
20.4





(Keratinocytes)





TNF alpha + IL-





1beta


LAK cells IL-2
6.8
27.5
Liver cirrhosis
25.5
19.9


LAK cells IL-
37.1
11.6
Lupus kidney
44.4
15.7


2 + IL-12


LAK cells IL-
20.7
19.1
NCI-H292 none
79.6
64.6


2 + IFN gamma


LAK cells IL-2 +
21.9
14.7
NCI-H292 IL-4
85.3
96.6


IL-18


LAK cells
4.7
3.3
NCI-H292 IL-9
100.0
98.6


PMA/ionomycin


NK Cells IL-2 rest
11.9
11.3
NCI-H292 IL-13
68.8
50.7


Two Way MLR 3
23.7
11.0
NCI-H292 IFN
80.1
56.6


day


gamma


Two Way MLR 5
12.5
6.1
HPAEC none
38.4
27.2


day


Two Way MLR 7
12.3
8.7
HPAEC TNF
42.6
43.2


day


alpha + IL-1beta


PBMC rest
6.0
5.7
Lung fibroblast
31.2
21.3





none


PBMC PWM
40.3
27.7
Lung fibroblast
14.7
24.5





TNF alpha + IL-





1beta


PBMC PHA-L
37.9
17.7
Lung fibroblast
47.0
42.6





IL-4


Ramos (B cell)
11.7
14.9
Lung fibroblast
49.3
30.6


none


IL-9


Ramos (B cell)
33.9
26.8
Lung fibroblast
36.6
42.6


ionomycin


IL-13


B lymphocytes
33.7
40.9
Lung fibroblast
44.8
22.5


PWM


IFN gamma


B lymphocytes
34.4
18.3
Dermal fibroblast
33.7
47.3


CD40L and IL-4


CCD1070 rest


EOL-1 dbcAMP
50.0
28.1
Dermal fibroblast
47.3
33.2





CCD1070 TNF





alpha


EOL-1 dbcAMP
44.1
32.1
Dermal fibroblast
50.0
34.6


PMA/ionomycin


CCD1070 IL-





1beta


Dendritic cells
33.9
19.6
Dermal fibroblast
24.0
34.4


none


IFN gamma


Dendritic cells LPS
21.9
10.2
Dermal fibroblast
24.3
32.8





IL-4


Dendritic cells
49.7
33.9
IBD Colitis 2
6.0
11.7


anti-CD40


Monocytes rest
10.7
10.3
IBD Crohn's
25.3
26.1


Monocytes LPS
30.6
9.3
Colon
70.7
100.0


Macrophages rest
41.2
33.7
Lung
64.6
17.7


Macrophages LPS
20.0
7.5
Thymus
80.7
56.3


HUVEC none
26.8
29.5
Kidney
26.4
41.5


HUVEC starved
26.2
37.6










[1463] CNS_neurodegeneration_v1.0 Summary: Ag3218/Ag3378—Two different experiments using probe/primer sets with the same sequence are in very good agreement. This panel confirms the expression of this gene at low levels to moderate levels in the brain in an independent group of individuals. However, no differential expression of this gene was detected, between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.3D for a discussion of the potential utility of this gene in treatment of central nervous system disorders.


[1464] Panel 1.3D Summary: Ag3218/Ag3378—Two different experiments using probe/primer sets with the same sequence are in good agreement. Highest expression is seen in testis and a lung cancer cell line (CTs=30-31). This panel confirms the expression of this gene at low levels in the brain. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[1465] This gene product is also expressed in adipose, pancreas, thyroid, pituitary, heart, and liver. This widespread expression in tissues with metabolic function suggests that this gene product may be important for the pathogenesis, diagnosis, and/or treatment of metabolic and endocrine diseases, including obesity and Types 1 and 2 diabetes.


[1466] Based on expression in this panel, this gene may be involved in gastric, pancreatic, brain, colon, renal, lung, breast, ovarian and prostate cancer as well as melanomas. Thus, expression of this gene could be used as a diagnostic marker for the presence of these cancers. Furthermore, therapeutic inhibition using antibodies or small molecule drugs might be of use in the treatment of these cancers.


[1467] Panel 2.2 Summary: Ag3218—This gene is expressed at low to moderate levels in many samples on this panel, with the highest levels of expression in breast cancer sample OD04590-01 (CT=30.3). This gene is expressed in a cluster of breast cancer samples with no expression in normal breast (CTh35). Similarly, this gene is expressed in ovarian cancer samples at higher levels than the matched margin samples.


[1468] Interestingly, this gene is expressed at higher levels in kidney cancer margin samples than in the matched cancer samples.


[1469] This gene is homologous to a mouse myosin phosphatase targeting subunit (MYPT) which have been found to play a role in cell division. MYPT undergoes mitosis-specific phosphorylation which is reversed during cytokinesis.



REFERENCES

[1470] 1. Totsukawa G, Yamakita Y, Yamashiro S, Hosoya H, Hartshorne D J, Matsumura F. Activation of myosin phosphatase targeting subunit by mitosis-specific phosphorylation. J Cell Biol Feb. 22, 1999;144(4):735-44.


[1471] Panel 4D Summary: Ag3218/Ag3378—Two different experiments using probe/primer sets with the same sequence are in very good agreement. Highest expression is seen in the colon and a mucoepidermoid cell line (CTs=30-32). This gene is expressed at low to moderate levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.


[1472] AG. CG59241-01: Amiloride-Sensitive Sodium Channel


[1473] Expression of gene CG59241-01 was assessed using the primer-probe set Ag3407, described in Table AGA. Results of the RTQ-PCR runs are shown in Tables AGB, AGC and AGD.


[1474] Table AGA. Probe Name Ag3407
796TABLE AGAProbe Name Ag3407StartSEQ IDPrimersSequencesLengthPostionNO:Forward5′-gtcaccctctgcaacactaatg-3′22268496ProbeTET-5′-ctgtcccagctcagctaccctgactt-3′-TAMRA26298497Reverse5′-tttcatccagtcccagcat-3′19340498


[1475]

797





TABLE AGB










CNS_neurodegeneration_v1.0











Rel. Exp. (%) Ag3407,

Rel. Exp. (%) Ag3407,


Tissue Name
Run 210349883
Tissue Name
Run 210349883













AD 1 Hippo
18.4
Control (Path) 3
4.1




Temporal Ctx


AD 2 Hippo
29.7
Control (Path) 4
40.3




Temporal Ctx


AD 3 Hippo
18.3
AD 1 Occipital
36.9




Ctx


AD 4 Hippo
5.4
AD 2 Occipital
0.0




Ctx (Missing)


AD 5 hippo
91.4
AD 3 Occipital
19.1




Ctx


AD 6 Hippo
80.7
AD 4 Occipital
18.8




Ctx


Control 2 Hippo
9.3
AD 5 Occipital
18.3




Ctx


Control 4 Hippo
19.9
AD 6 Occipital
28.9




Ctx


Control (Path) 3
8.8
Control 1 Occipital
4.3


Hippo

Ctx


AD 1 Temporal Ctx
28.5
Control 2 Occipital
80.1




Ctx


AD 2 Temporal Ctx
41.8
Control 3 Occipital
20.2




Ctx


AD 3 Temporal Ctx
32.5
Control 4 Occipital
6.0




Ctx


AD 4 Temporal Ctx
36.3
Control (Path) 1
92.7




Occipital Ctx


AD 5 Inf Temporal
100.0
Control (Path) 2
25.3


Ctx

Occipital Ctx


AD 5 SupTemporal
56.6
Control (Path) 3
3.0


Ctx

Occipital Ctx


AD 6 Inf Temporal
82.4
Control (Path) 4
41.2


Ctx

Occipital Ctx


AD 6 Sup Temporal
44.1
Control 1 Parietal
21.9


Ctx

Ctx


Control 1 Temporal
15.3
Control 2 Parietal
79.0


Ctx

Ctx


Control 2 Temporal
24.1
Control 3 Parietal
22.2


Ctx

Ctx


Control 3 Temporal
34.6
Control (Path) 1
77.9


Ctx

Parietal Ctx


Control 4 Temporal
12.0
Control (Path) 2
47.6


Ctx

Parietal Ctx


Control (Path) 1
53.6
Control (Path) 3
6.2


Temporal Ctx

Parietal Ctx


Control (Path) 2
56.6
Control (Path) 4
67.4


Temporal Ctx

Parietal Ctx










[1476]

798





TABLE AGC










General_screening_panel_v1.4











Rel. Exp. (%)

Rel. Exp. (%)



Ag3407, Run

Ag3407, Run


Tissue Name
216821458
Tissue Name
216821458













Adipose
0.2
Renal ca. TK-10
16.6


Melanoma*
2.3
Bladder
0.3


Hs688(A).T


Melanoma*
0.4
Gastric ca. (liver met.)
8.8


Hs688(B).T

NCI-N87


Melanoma* M14
2.0
Gastric ca. KATO III
0.7


Melanoma*
2.5
Colon ca. SW-948
3.7


LOXIMVI


Melanoma* SK-
8.7
Colon ca. SW480
14.1


MEL-5


Squamous cell
1.2
Colon ca.* (SW480
21.2


carcinoma SCC-4

met) SW620


Testis Pool
0.4
Colon ca. HT29
10.7


Prostate ca.* (bone
4.4
Colon ca. HCT-116
64.2


met) PC-3


Prostate Pool
2.3
Colon ca. CaCo-2
32.3


Placenta
0.5
Colon cancer tissue
13.2


Uterus Pool
0.0
Colon ca. SW1116
12.5


Ovarian ca.
8.4
Colon ca. Colo-205
0.3


OVCAR-3


Ovarian ca. SK-
9.7
Colon ca. SW-48
0.6


OV-3


Ovarian ca.
1.6
Colon Pool
2.8


OVCAR-4


Ovarian ca.
18.9
Small Intestine Pool
4.5


OVCAR-5


Ovarian ca.
4.9
Stomach Pool
1.4


IGROV-1


Ovarian ca.
5.9
Bone Marrow Pool
1.8


OVCAR-8


Ovary
2.0
Fetal Heart
2.4


Breast ca. MCF-7
16.7
Heart Pool
0.3


Breast ca. MDA-
12.1
Lymph Node Pool
3.5


MB-231


Breast ca. BT 549
22.7
Fetal Skeletal Muscle
1.9


Breast ca. T47D
27.4
Skeletal Muscle Pool
0.0


Breast ca. MDA-N
4.5
Spleen Pool
0.0


Breast Pool
2.9
Thymus Pool
2.1


Trachea
9.0
CNS cancer
0.9




(glio/astro) U87-MG


Lung
0.0
CNS cancer
11.7




(glio/astro) U-118-MG


Fetal Lung
10.8
CNS cancer
58.6




(neuro; met) SK-N-AS


Lung ca. NCI-N417
1.3
CNS cancer (astro) SF-
28.1




539


Lung ca. LX-1
21.8
CNS cancer (astro)
24.7




SNB-75


Lung ca. NCI-H146
5.4
CNS cancer (glio)
7.3




SNB-19


Lung ca. SHP-77
11.7
CNS cancer (glio) SF-
4.8




295


Lung ca. A549
8.0
Brain (Amygdala) Pool
3.9


Lung ca. NCI-H526
0.0
Brain (cerebellum)
36.1


Lung ca. NCI-H23
7.4
Brain (fetal)
100.0


Lung ca. NCI-H460
5.4
Brain (Hippocampus)
5.6




Pool


Lung ca. HOP-62
2.9
Cerebral Cortex Pool
5.6


Lung ca. NCI-H522
8.5
Brain (Substantia
7.1




nigra) Pool


Liver
0.0
Brain (Thalamus) Pool
11.3


Fetal Liver
0.0
Brain (whole)
13.4


Liver ca. HepG2
0.8
Spinal Cord Pool
12.7


Kidney Pool
2.1
Adrenal Gland
0.0


Fetal Kidney
3.7
Pituitary gland Pool
0.0


Renal ca. 786-0
1.7
Salivary Gland
0.9


Renal ca. A498
0.7
Thyroid (female)
0.0


Renal ca. ACHN
1.9
Pancreatic ca.
2.3




CAPAN2


Renal ca. UO-31
0.2
Pancreas Pool
2.6










[1477]

799





TABLE AGD










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3407, Run

Ag3407, Run


Tissue Name
165296462
Tissue Name
165296462













Secondary Th1 act
7.9
HUVEC IL-1beta
0.0


Secondary Th2 act
17.1
HUVEC IFN gamma
0.0


Secondary Tr1 act
40.1
HUVEC TNF alpha +
0.0




IFN gamma


Secondary Th1 rest
4.4
HUVEC TNF alpha +
0.0




IL4


Secondary Th2 rest
7.0
HUVEC IL-11
0.0


Secondary Tr1 rest
11.7
Lung Microvascular EC
0.0




none


Primary Th1 act
61.1
Lung Microvascular EC
0.0




TNF alpha + IL-1beta


Primary Th2 act
69.3
Microvascular Dermal
0.0




EC none


Primary Tr1 act
90.8
Microsvasular Dermal
0.0




EC TNF alpha + IL-1beta


Primary Th1 rest
20.0
Bronchial epithelium
0.0




TNF alpha + IL1beta


Primary Th2 rest
42.6
Small airway epithelium
3.0




none


Primary Tr1 rest
52.5
Small airway epithelium
0.0




TNF alpha + IL-1beta


CD45RA CD4
2.8
Coronery artery SMC rest
3.6


lymphocyte act


CD45RO CD4
14.0
Coronery artery SMC
0.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
5.8
Astrocytes rest
11.6


Secondary CD8
18.9
Astrocytes TNF alpha +
0.0


lymphocyte rest

IL-1beta


Secondary CD8
22.2
KU-812 (Basophil) rest
0.0


lymphocyte act


CD4 lymphocyte none
0.0
KU-812 (Basophil)
0.0




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
4.5
CCD1106
2.7


CD95 CH11

(Keratinocytes) none


LAK cells rest
3.3
CCD1106
0.0




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
4.0
Liver cirrhosis
13.5


LAK cells IL-2 + IL-12
5.7
Lupus kidney
4.1


LAK cells IL-2 + IFN
21.3
NCI-H292 none
9.0


gamma


LAK cells IL-2 + IL-18
6.7
NCI-H292 IL-4
14.8


LAK cells
0.0
NCI-H292 IL-9
3.5


PMA/ionomycin


NK Cells IL-2 rest
0.0
NCI-H292 IL-13
0.0


Two Way MLR 3 day
5.0
NCI-H292 IFN gamma
5.5


Two Way MLR 5 day
2.3
HPAEC none
0.0


Two Way MLR 7 day
8.2
HPAEC TNF alpha + IL-
0.0




1beta


PBMC rest
0.0
Lung fibroblast none
2.8


PBMC PWM
21.3
Lung fibroblast TNF
0.0




alpha + IL-1beta


PBMC PHA-L
20.4
Lung fibroblast IL-4
0.0


Ramos (B cell) none
0.0
Lung fibroblast IL-9
0.0


Ramos (B cell)
2.8
Lung fibroblast IL-13
0.0


ionomycin


B lymphocytes PWM
100.0
Lung fibroblast IFN
1.4




gamma


B lymphocytes CD40L
19.8
Dermal fibroblast
34.4


and IL-4

CCD1070 rest


EOL-1 dbcAMP
2.6
Dermal fibroblast
68.8




CCD1070 TNF alpha


EOL-1 dbcAMP
6.2
Dermal fibroblast
0.0


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
0.0
Dermal fibroblast IFN
0.0




gamma


Dendritic cells LPS
0.0
Dermal fibroblast IL-4
14.1


Dendritic cells anti-
6.0
IBD Colitis 2
0.0


CD40


Monocytes rest
0.0
IBD Crohn's
0.0


Monocytes LPS
6.5
Colon
42.3


Macrophages rest
0.0
Lung
35.8


Macrophages LPS
0.0
Thymus
45.4


HUVEC none
0.0
Kidney
55.1


HUVEC starved
0.0










[1478] CNS_neurodegeneration_v1.0 Summary: Ag3407 This panel confirms the expression of this gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.


[1479] General_screening_panel_v1.4 Summary: Ag3407 Highest expression of the CG59241-01 gene is seen in fetal brain (CT=31.3). Furthermore, low to moderate levels of expression is also observed in CNS cancer cell lines (CTs=32-34). The CG59241-01 gene codes for a putative amiloride-sensitive sodium channel. A similar amiloride-sensitive sodium channel was shown to be highly expressed in malignant glioblastoma multiforme tumors and to be a charachteristic feature of malignant brain tumor cells (Ref. 1). Therefore, therapeutic modulation of the activity of the protein encoded by this gene may be beneficial in the treatment of CNS cancer. Significant expression is also seen in a cluster of cell lines derived from brain, colon, breast, and ovarian cancers. Therefore, therapeutic modulation of the activity of this gene or its protein product, through the use of small molecule drugs, protein therapeutics or antibodies, might be beneficial in the treatment of these cancers.


[1480] In addition, this gene is expressed at low levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.



REFERENCES

[1481] 1. Bubien J K, Keeton D A, Fuller C M, Gillespie G Y, Reddy A T, Mapstone T B, Benos D J. (1999) Malignant human gliomas express an amiloride-sensitive Na+ conductance. Am J Physiol 276(6 Pt 1):C1405-10


[1482] Panel 4D Summary: Ag3407 Highest expression Of the CG59241-01 gene is detected in PWM treated B lymphocytes (CT=32). Similar expression is also detected in primary activated Th1, Th2 and Tr1 cells, as well as TNF alpha treated dermal fibroblast CCD1070 cells (CTs=32). Therefore, expression of this gene can be used to distinguish these samples from other samples in the panel. Furthermore, this gene is expressed in activated lymphocytes. Likewise, no expression of this gene is seen in PBMC that contain normal B cells (CTr=40), but it is induced when PBMC are treated with the pokeweed mitogen or PHA-L (CTs=34). In addition, the transcript is not seen in the B cell lymphoma Ramos regardless of stimulation. Therefore, the gene product could potentially be used therapeutically in the treatment of Crohn's disease, ulcerative colitis, multiple sclerosis, chronic obstructive pulmonary disease, asthma, emphysema, rheumatoid arthritis, lupus erythematosus, psoriasis and in other diseases in which T cells and B cells are activated.


[1483] In addition, low expression of this gene is also observed in normal colon, lung, thymus and kidney tissues. The CG59241-01 gene encodes an amiloride-sensitive sodium channel, A similar channel, the amiloride-sensitive epithelial sodium channel (ENaC) constitutes the limiting step for sodium reabsorption in epithelial cells that line the distal nephron, distal colon, ducts of several exocrine glands and lung airways and plays an important role in pathophysiological and clinical conditions such as hypertension or lung edema. ENaC has been implicated in two genetic diseases, Liddle's syndrome and pseudoeiypoaldosteronism (PHA-1) (Ref. 1). Therefore, antibody or small molecule therapies designed with the protein encoded for by CG59241-01 gene could modulate kidney/colon/lung function and be important in the treatment of inflammatory or autoimmune diseases of these tissues in addition to hypertension, lung edema, Liddle's syndrom and PHA-1.



REFERENCE

[1484] 1. Hummler E. (11998) Reversal of convention: from man to experimental animal in elucidating the function of the renal amiloride-sensitive sodium channel. Exp Nephrol July-August 1998;6(4):265-71


[1485] AH. CG58602-01: FAD Binding Domain Containing Protein


[1486] Expression of gene CG58602-01 was assessed using the primer-probe set Ag3385, described in Table AHA. Results of the RTQ-PCR runs are shown in Tables AHB, AHC and AHD.


[1487] Table AHA. Probe Name Ag3385
800TABLE AHAProbe Name Ag3385StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-tcatgaatccaggcaaagtg-3′201427499ProbeTET-5′-ttagcccacaagttccctgactacgg-3′-TAMRA261468500Reverse5′-tggcatgaagaaaagttcca-3′201503501


[1488]

801





TABLE AHB










CNS_neurodegeneration_v1.0











Rel. Exp. (%) Ag3385,

Rel. Exp. (%) Ag3385,


Tissue Name
Run 210154892
Tissue Name
Run 210154892













AD 1 Hippo
34.6
Control (Path) 3
21.2




Temporal Ctx


AD 2 Hippo
47.6
Control (Path) 4
36.1




Temporal Ctx


AD 3 Hippo
11.9
AD 1 Occipital Ctx
28.1


AD 4 Hippo
24.3
AD 2 Occipital Ctx
0.0




(Missing)


AD 5 Hippo
56.3
AD 3 Occipital Ctx
15.0


AD 6 Hippo
63.3
AD 4 Occipital Ctx
34.9


Control 2 Hippo
42.6
AD 5 Occipital Ctx
52.1


Control 4 Hippo
24.7
AD 6 Occipital Ctx
25.3


Control (Path) 3
23.3
Control 1 Occipital
14.3


Hippo

Ctx


AD 1 Temporal
23.8
Control 2 Occipital
69.3


Ctx

Ctx


AD 2 Temporal
73.7
Control 3 Occipital
29.5


Ctx

Ctx


AD 3 Temporal
7.3
Control 4 Occipital
14.9


Ctx

Ctx


AD 4 Temporal
39.0
Control (Path) 1
68.3


Ctx

Occipital Ctx


AD 5 Inf Temporal
100.0
Control (Path) 2
11.0


Ctx

Occipital Ctx


AD 5 Sup
55.5
Control (Path) 3
8.9


Temporal Ctx

Occipital Ctx


AD 6 Inf Temporal
64.2
Control (Path) 4
17.3


Ctx

Occipital Ctx


AD 6 Sup
54.0
Control 1 Parietal
32.8


Temporal Ctx

Ctx


Control 1
23.8
Control 2 Parietal
62.0


Temporal Ctx

Ctx


Control 2
50.3
Control 3 Parietal
33.4


Temporal Ctx

Ctx


Control 3
38.4
Control (Path) 1
70.7


Temporal Ctx

Parietal Ctx


Control 3
19.2
Control (Path) 2
31.4


Temporal Ctx

Parietal Ctx


Control (Path) 1
56.6
Control (Path) 3
20.9


Temporal Ctx

Parietal Ctx


Control (Path) 2
47.6
Control (Path) 4
43.2


Temporal Ctx

Parietal Ctx










[1489]

802





TABLE AHC










General_screening_panel_v1.4











Rel. Exp. (%)

Rel. Exp. (%)



Ag3385, Run

Ag3385, Run


Tissue Name
217043538
Tissue Name
217043538













Adipose
2.4
Renal ca. TK-10
3.5


Melanoma*
0.7
Bladder
6.6


Hs688(A).T


Melanoma*
1.1
Gastric ca. (liver met.)
2.1


Hs688(B).T

NCI-N87


Melanoma* M14
0.9
Gastric ca. KATO III
0.9


Melanoma*
1.3
Colon ca. SW-948
4.5


LOXIMVI


Melanoma* SK-
2.2
Colon ca. SW480
0.8


MEL-5


Squamous cell
0.1
Colon ca.* (SW480
1.3


carcinoma SCC-4

met) SW620


Testis Pool
1.3
Colon ca. HT29
0.6


Prostate ca.* (bone
5.8
Colon ca. HCT-116
1.9


met) PC-3


Prostate Pool
4.0
Colon ca. CaCo-2
28.5


Placenta
2.5
Colon cancer tissue
2.0


Uterus Pool
0.5
Colon ca. SW1116
0.9


Ovarian ca.
1.1
Colon ca. Colo-205
3.5


OVCAR-3


Ovarian ca. SK-
3.7
Colon ca. SW-48
4.2


OV-3


Ovarian ca.
0.2
Colon Pool
3.0


OVCAR-4


Ovarian ca.
42.0
Small Intestine Pool
3.5


OVCAR-5


Ovarian ca.
8.0
Stomach Pool
1.8


IGROV-1


Ovarian ca.
2.7
Bone Marrow Pool
0.9


OVCAR-8


Ovary
3.3
Fetal Heart
12.9


Breast ca. MCF-7
10.3
Heart Pool
8.3


Breast ca. MDA-
3.0
Lymph Node Pool
3.5


MB-231


Breast ca. BT 549
1.3
Fetal Skeletal Muscle
2.6


Breast ca. T47D
100.0
Skeletal Muscle Pool
25.5


Breast ca. MDA-N
0.4
Spleen Pool
0.2


Breast Pool
3.1
Thymus Pool
2.7


Trachea
3.2
CNS cancer
4.0




(glio/astro) U87-MG


Lung
2.9
CNS cancer
1.3




(glio/astro) U-118-MG


Fetal Lung
3.0
CNS cancer
1.8




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.2
CNS cancer (astro) SF-
1.3




539


Lung ca. LX-1
1.1
CNS cancer (astro)
0.9




SNB-75


Lung ca. NCI-H146
0.4
CNS cancer (glio)
5.0




SNB-19


Lung ca. SHP-77
3.1
CNS cancer (glio) SF-
5.5




295


Lung ca. A549
4.3
Brain (Amygdala) Pool
5.5


Lung ca. NCI-H526
0.4
Brain (cerebellum)
13.5


Lung ca. NCI-H23
6.8
Brain (fetal)
5.6


Lung ca. NCI-H460
1.5
Brain Hippocampus)
5.2




Pool


Lung ca. HOP-62
0.1
Cerebral Cortex Pool
7.1


Lung ca. NCI-H522
3.6
Brain (Substantia
11.5




nigra) Pool


Liver
13.6
Brain (Thalamus) Pool
7.2


Fetal Liver
12.0
Brain (whole)
7.2


Liver ca. HepG2
2.7
Spinal Cord Pool
4.8


Kidney Pool
6.2
Adrenal Gland
6.0


Fetal Kidney
4.0
Pituitary gland Pool
1.7


Renal ca. 786-0
0.2
Salivary Gland
6.6


Renal ca. A498
1.4
Thyroid (female)
5.2


Renal ca. ACHN
0.8
Pancreatic ca.
3.5




CAPAN2


Renal ca. UO-31
0.9
Pancreas Pool
4.4










[1490]

803





TABLE AHD










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3385, Run

Ag3385, Run


Tissue Name
165296471
Tissue Name
165296471













Secondary Th1 act
1.2
HUVEC IL-1beta
0.0


Secondary Th2 act
3.6
HUVEC IFN gamma
3.7


Secondary Tr1 act
2.6
HUVEC TNF alpha +
0.7




IFN gamma


Secondary Th1 rest
0.4
HUVEC TNF alpha +
2.2




IL4


Secondary Th2 rest
0.9
HUVEC IL-11
1.3


Secondary Tr1 rest
0.4
Lung Microvascular EC
3.2




none


Primary Th1 act
1.1
Lung Microvascular EC
1.5




TNF alpha + IL-1beta


Primary Th2 act
0.7
Microvascular Dermal
3.0




EC none


Primary Tr1 act
0.0
Microsvasular Dermal
0.0




EC TNF alpha + IL-1beta


Primary Th1 rest
1.1
Bronchial epithelium
0.6




TNF alpha + IL-1beta


Primary Th2 rest
0.5
Small airway epithelium
0.7




none


Primary Tr1 rest
0.6
Small airway epithelium
0.8




TNF alpha + IL-1beta


CD45RA CD4
2.0
Coronery artery SMC rest
0.5


lymphocyte act


CD45RO CD4
3.7
Coronery artery SMC
2.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
0.9
Astrocytes rest
1.5


Secondary CD8
2.7
Astrocytes TNF alpha +
2.6


lymphocyte rest

IL-1beta


Secondary CD8
0.0
KU-812 (Basophil) rest
3.0


lymphocyte act


CD4 lymphocyte none
0.0
KU-812 (Basophil)
8.2




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
0.0
CCD1106
3.3


CD95 CH11

(Keratinocytes) none


LAK cells rest
9.4
CCD1106
0.3




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
0.8
Liver cirrhosis
7.9


LAK cells IL-2 + IL-12
1.5
Lupus kidney
2.3


LAK cells IL-2 + IFN
3.7
NCI-H292 none
3.3


gamma


LAK cells IL-2 + IL-18
2.5
NCI-H292 IL-4
8.4


LAK cells
2.0
NCI-H292 IL-9
2.6


PMA/ionomycin


NK Cells IL-2 rest
0.7
NCI-H292 IL-13
2.9


Two Way MLR 3 day
4.6
NCI-H292 IFN gamma
1.8


Two Way MLR 5 day
2.8
HPAEC none
2.3


Two Way MLR 7 day
1.8
HPAEC TNF alpha + IL-
1.9




1beta


PBMC rest
0.6
Lung fibroblast none
1.5


PBMC PWM
11.0
Lung fibroblast TNF
0.7




alpha + IL-1beta


PBMC PHA-L
2.3
Lung fibroblast IL-4
1.6


Ramos (B cell) none
0.0
Lung fibroblast IL-9
2.0


Ramos (B cell)
0.9
Lung fibroblast IL-13
0.9


ionomycin


B lymphocytes PWM
3.5
Lung fibroblast IFN
0.7




gamma


B lymphocytes CD40L
5.4
Dermal fibroblast
1.6


and IL-4

CCD1070 rest


EOL-1 dbcAMP
5.0
Dermal fibroblast
0.0




CCD1070 TNF alpha


EOL-1 dbcAMP
1.2
Dermal fibroblast
2.3


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
15.5
Dermal fibroblast IFN
0.5




gamma


Dendritic cells LPS
4.5
Dermal fibroblast IL-4
0.4


Dendritic cells anti-
11.7
IBD Colitis 2
0.3


CD40


Monocytes rest
8.7
IBD Crohn's
0.0


Monocytes LPS
0.6
Colon
5.1


Macrophages rest
13.5
Lung
6.7


Macrophages LPS
1.6
Thymus
100.0


HUVEC none
0.6
Kidney
11.3


HUVEC starved
1.7










[1491] CNS_neurodegeneration_v1.0 Summary: Ag3385 This panel confirms the expression of CG58602-01 gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.


[1492] General_screening_panel_v1.4 Summary: Ag3385 Highest expression of the CG58602-01 gene is seen in a breast cancer cell line (CT=26.3). Significant expression is also seen in an ovarian cancer cell line. Thus, expression of this gene could be used to differentiate between these samples and other samples on this panel and as a marker to detect the presence of breast and ovarian cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of breast and ovarian cancers.


[1493] Among tissues with metabolic function, this gene is expressed at moderate to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.


[1494] Expression of this gene is higher in fetal skeletal muscle (CT=28.3) when compared to expression in adult skeletal muscle (CT=31.5). Thus, expression of this gene could be used to distinguish fetal from adult skeletal muscle.


[1495] In addition, this gene is expressed at high levels (CTs=29-30.4) in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[1496] Panel 4D Summary: Ag3385 Highest expression of the CG58602-01 gene is seen in the thymus (CT=28). Thus, the putative protein encoded for by this gene could therefore play an important role in T cell development. Therefore, small molecule therapeutics designed against the proetin encoded by this gene could be utilized to modulate immune function (T cell development) and be important for organ transplant, AIDS treatment or post chemotherapy immune reconstitiution.


[1497] AI. CG58468-01: Serum Amyloid P Component


[1498] Expression of gene CG58468-01 was assessed using the primer-probe set Ag3356, described in Table AIA. Results of the RTQ-PCR runs are shown in Table AIB.


[1499] Table AIA. Probe Name Ag3356
804TABLE AIAProbe Name Ag3356StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-aggcatttattttccctcaaga-3′22106502ProbeTET-5′-agtctatgtgtccctgatccccaagg-3′-TAMRA26137503Reverse5′-gttttcaggcaaagcttgaagt-3′22181504


[1500]

805





TABLE AIB










General_screening_panel_v1.4











Rel. Exp. (%)

Rel. Exp. (%)



Ag3356, Run

Ag3356, Run


Tissue Name
216523476
Tissue Name
216523476













Adipose
2.2
Renal ca. TK-10
0.0


Melanoma*
0.0
Bladder
0.0


Hs688(A).T


Melanoma*
0.0
Gastric ca. (liver met.)
0.0


Hs688(B).T

NCI-N87


Melanoma* M14
0.0
Gastric ca. KATO III
0.0


Melanoma*
0.0
Colon ca. SW-948
0.0


LOXIMVI


Melanoma* SK-
0.0
Colon ca. SW480
0.0


MEL-5


Squamous cell
0.0
Colon ca.* (SW480
0.0


carcinoma SCC-4

met) SW620


Testis Pool
1.7
Colon ca. HT29
0.0


Prostate ca.* (bone
0.0
Colon ca. HCT-116
0.0


met) PC-3


Prostate Pool
0.0
Colon ca. CaCo-2
0.0


Placenta
0.0
Colon cancer tissue
0.0


Uterus Pool
0.0
Colon ca. SW1116
0.0


Ovarian ca.
0.0
Colon ca. Colo-205
0.0


OVCAR-3


Ovarian ca. SK-
0.0
Colon ca. SW-48
0.0


OV-3


Ovarian ca.
0.0
Colon Pool
100.0


OVCAR-4


Ovarian ca.
0.0
Small Intestine Pool
5.6


OVCAR-5


Ovarian ca.
0.0
Stomach Pool
0.0


IGROV-1


Ovarian ca.
0.0
Bone Marrow Pool
10.7


OVCAR-8


Ovary
0.0
Fetal Heart
0.0


Breast ca. MCF-7
0.0
Heart Pool
2.6


Breast ca. MDA-
0.0
Lymph Node Pool
25.9


MB-231


Breast ca. BT 549
0.0
Fetal Skeletal Muscle
2.1


Breast ca. T47D
0.0
Skeletal Muscle Pool
0.0


Breast ca. MDA-N
0.0
Spleen Pool
0.0


Breast Pool
19.6
Thymus Pool
0.0


Trachea
1.5
CNS cancer
0.0




(glio/astro) U87-MG


Lung
0.0
CNS cancer
0.0




(glio/astro) U-118-MG


Fetal Lung
5.0
CNS cancer
0.0




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.0
CNS cancer (astro) SF-
0.0




539


Lung ca. LX-1
0.0
CNS cancer (astro)
0.0




SNB-75


Lung ca. NCI-H146
0.0
CNS cancer (glio)
0.0




SNB-19


Lung ca. SHP-77
0.0
CNS cancer (glio) SF-
0.0




295


Lung ca. A549
0.0
Brain (Amygdala) Pool
0.0


Lung ca. NCI-H526
0.0
Brain (cerebellum)
0.0


Lung ca. NCI-H23
38.7
Brain (fetal)
2.6


Lung ca. NCI-H460
0.0
Brain (Hippocampus)
0.0




Pool


Lung ca. HOP-62
0.0
Cerebral Cortex Pool
0.0


Lung ca. NCI-H522
0.0
Brain (Substantia
0.0




nigra) Pool


Liver
2.3
Brain (Thalamus) Pool
0.0


Fetal Liver
0.0
Brain (whole)
0.0


Liver ca. HepG2
0.0
Spinal Cord Pool
2.1


Kidney Pool
19.1
Adrenal Gland
0.0


Fetal Kidney
0.0
Pituitary gland Pool
2.1


Renal ca. 786-0
0.0
Salivary Gland
0.0


Renal ca. A498
0.0
Thyroid (female)
0.0


Renal ca. ACHN
0.0
Pancreatic ca.
0.0




CAPAN2


Renal ca. UO-31
0.0
Pancreas Pool
7.2










[1501] CNS_neurodegeneration_v1.0 Summary: Ag3356 Expression of the CG58468-01 gene is low/undetectable in all the samples on this panel. (CTs>35). (Data not shown.)


[1502] General_screening_panel_v1.4 Summary: Ag3356 Expression of the CG58468-01 gene is restricted to the colon (CT=34). Thus, expression of this gene could be used to differentiate between this sample and other samples on this panel.


[1503] Panel 4D Summary: Ag3356 Results from one experiment with the CG56003-01 gene are not included. The amp plot indicates that there were experimental difficulties with this run.


[1504] AJ. CG58183-01: N-Methyl-D-Aspartate Receptor


[1505] Expression of gene CG58183-01 was assessed using the primer-probe set Ag3355, described in Table AJA. Results of the RTQ-PCR runs are shown in Tables AJB, AJC and AJD.


[1506] Table AJA. Probe Name Ag3355
806TABLE AJAProbe Name Ag3355StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-gctggccaactctgtctagac-3′211617505ProbeTET-5′-tgactcttccacattggacagccttt-3′-TAMRA261649506Reverse5′-ttactgctatggaggctgctaa-3′221675507


[1507]

807





TABLE AJB










CNS_neurodegeneration_v1.0











Rel. Exp. (%) Ag3355,

Rel. Exp. (%) Ag3355,


Tissue Name
Run 210142850
Tissue Name
Run 210142850













AD 1 Hippo
17.7
Control (Path) 3
7.3




Temporal Ctx


AD 2 Hippo
27.4
Control (Path) 4
47.6




Temporal Ctx


AD 3 Hippo
8.8
AD 1 Occipital Ctx
18.8


AD 4 Hippo
16.2
AD 2 Occipital Ctx
0.0




(Missing)


AD 5 Hippo
53.6
AD 3 Occipital Ctx
3.0


AD 6 Hippo
51.4
AD 4 Occipital Ctx
27.2


Control 2 Hippo
41.8
AD 5 Occipital Ctx
55.1


Control 4 Hippo
10.4
AD 6 Occipital Ctx
6.3


Control (Path) 3
4.5
Control 1 Occipital
2.8


Hippo

Ctx


AD 1 Temporal
18.3
Control 2 Occipital
39.0


Ctx

Ctx


AD 2 Temporal
48.0
Control 3 Occipital
18.2


Ctx

Ctx


AD 3 Temporal
5.7
Control 4 Occipital
3.4


Ctx

Ctx


AD 4 Temporal
15.2
Control (Path) 1
81.8


Ctx

Occipital Ctx


AD 5 Inf
61.6
Control (Path) 2
9.0


Temporal Ctx

Occipital Ctx


AD 5 Sup
69.3
Control (Path) 3
0.0


Temporal Ctx

Occipital Ctx


AD 6 Inf
66.9
Control (Path) 4
13.3


Temporal Ctx

Occipital Ctx


AD 6 Sup
62.9
Control 1 Parietal
6.6


Temporal Ctx

Ctx


Control 1
8.5
Control 2 Parietal
74.7


Temporal Ctx

Ctx


Control 2
66.9
Control 3 Parietal
21.0


Temporal Ctx

Ctx


Control 3
34.9
Control (Path) 1
100.0


Temporal Ctx

Parietal Ctx


Control 3
7.0
Control (Path) 2
21.9


Temporal Ctx

Parietal Ctx


Control (Path) 1
90.1
Control (Path) 3
6.0


Temporal Ctx

Parietal Ctx


Control (Path) 2
74.7
Control (Path) 4
50.7


Temporal Ctx

Parietal Ctx










[1508]

808





TABLE AJC










General_screening_panel_v1.4











Rel. Exp. (%)

Rel. Exp. (%)



Ag3355, Run

Ag3355, Run


Tissue Name
216523475
Tissue Name
216523475













Adipose
0.0
Renal ca. TK-10
0.0


Melanoma*
0.9
Bladder
0.0


Hs688(A).T


Melanoma*
0.0
Gastric ca. (liver met.)
0.0


Hs688(B).T

NCI-N87


Melanoma* M14
0.0
Gastric ca. KATO III
0.0


Melanoma*
0.0
Colon ca. SW-948
0.0


LOXIMVI


Melanoma* SK-
0.0
Colon ca. SW480
0.2


MEL-5


Squamous cell
0.0
Colon ca.* (SW480
0.0


carcinoma SCC-4

met) SW620


Testis Pool
2.4
Colon ca. HT29
0.0


Prostate ca.* (bone
0.0
Colon ca. HCT-116
0.0


met) PC-3


Prostate Pool
2.1
Colon ca. CaCo-2
0.0


Placenta
0.0
Colon cancer tissue
0.0


Uterus Pool
0.0
Colon ca. SW1116
0.0


Ovarian ca.
0.4
Colon ca. Colo-205
0.0


OVCAR-3


Ovarian ca. SK-
0.3
Colon ca. SW-48
0.0


OV-3


Ovarian ca.
0.0
Colon Pool
2.2


OVCAR-4


Ovarian ca.
0.0
Small Intestine Pool
3.4


OVCAR-5


Ovarian ca.
0.0
Stomach Pool
2.4


IGROV-1


Ovarian ca.
0.0
Bone Marrow Pool
1.5


OVCAR-8


Ovary
4.4
Fetal Heart
1.9


Breast ca. MCF-7
0.0
Heart Pool
3.6


Breast ca. MDA-
0.0
Lymph Node Pool
2.9


MB-231


Breast ca. BT 549
0.0
Fetal Skeletal Muscle
1.8


Breast ca. T47D
0.0
Skeletal Muscle Pool
0.0


Breast ca. MDA-N
0.0
Spleen Pool
4.3


Breast Pool
5.7
Thymus Pool
4.7


Trachea
1.7
CNS cancer
0.0




(glio/astro) U87-MG


Lung
1.6
CNS cancer
0.1




(glio/astro) U-118-MG


Fetal Lung
0.0
CNS cancer
3.2




(neuro; met) SK-N-AS


Lung ca. NCI-N417
17.8
CNS cancer (astro) SF-
14.8




539


Lung ca. LX-1
0.0
CNS cancer (astro)
17.6




SNB-75


Lung ca. NCI-H146
4.0
CNS cancer (glio)
0.0




SNB-19


Lung ca. SHP-77
11.7
CNS cancer (glio) SF-
0.0




295


Lung ca. A549
0.0
Brain (Amygdala) Pool
27.7


Lung ca. NCI-H526
0.3
Brain (cerebellum)
0.7


Lung ca. NCI-H23
1.9
Brain (fetal)
100.0


Lung ca. NCI-H460
0.3
Brain (Hippocampus)
33.0




Pool


Lung ca. HOP-62
0.3
Cerebral Cortex Pool
42.3


Lung ca. NCI-H522
0.0
Brain (Substantia
43.8




nigra) Pool


Liver
0.2
Brain (Thalamus) Pool
50.7


Fetal Liver
0.4
Brain (whole)
71.2


Liver ca. HepG2
0.0
Spinal Cord Pool
15.0


Kidney Pool
1.4
Adrenal Gland
0.0


Fetal Kidney
7.2
Pituitary gland Pool
0.0


Renal ca. 786-0
0.0
Salivary Gland
0.1


Renal ca. A498
0.0
Thyroid (female)
0.1


Renal ca. ACHN
0.0
Pancreatic ca.
0.0




CAPAN2


Renal ca. UO-31
0.0
Pancreas Pool
2.7










[1509]

809





TABLE AJD










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3355, Run

Ag3355, Run


Tissue Name
165241988
Tissue Name
165241988













Secondary Th1 act
0.0
HUVEC IL-1beta
0.0


Secondary Th2 act
0.0
HUVEC IFN gamma
0.0


Secondary Tr1 act
0.0
HUVEC TNF alpha +
0.0




IFN gamma


Secondary Th1 rest
0.0
HUVEC TNF alpha +
0.0




IL4


Secondary Th2 rest
11.8
HUVEC IL-11
0.0


Secondary Tr1 rest
0.0
Lung Microvascular EC
0.0




none


Primary Th1 act
0.0
Lung Microvascular EC
0.0




TNF alpha + IL-1beta


Primary Th2 act
0.0
Microvascular Dermal
0.0




EC none


Primary Tr1 act
0.0
Microsvasular Dermal
0.0




EC TNF alpha + IL-1beta


Primary Th1 rest
0.0
Bronchial epithelium
0.0




TNF alpha + IL1beta


Primary Th2 rest
0.0
Small airway epithelium
0.0




none


Primary Tr1 rest
0.0
Small airway epithelium
0.0




TNF alpha + IL-1beta


CD45RA CD4
0.0
Coronery artery SMC rest
0.0


lymphocyte act


CD45RO CD4
0.0
Coronery artery SMC
0.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
0.0
Astrocytes rest
0.0


Secondary CD8
0.0
Astrocytes TNF alpha +
57.8


lymphocyte rest

IL-1beta


Secondary CD8
0.0
KU-812 (Basophil) rest
0.0


lymphocyte act


CD4 lymphocyte none
0.0
KU-812 (Basophil)
67.4




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
0.0
CCD1106
0.0


CD95 CH11

(Keratinocytes) none


LAK cells rest
0.0
CCD1106
0.0




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
0.0
Liver cirrhosis
39.8


LAK cells IL-2 + IL-12
0.0
Lupus kidney
0.0


LAK cells IL-2 + IFN
0.0
NCI-H292 none
0.0


gamma


LAK cells IL-2 + IL-18
0.0
NCI-H292 IL-4
0.0


LAK cells
0.0
NCI-H292 IL-9
0.0


PMA/ionomycin


NK Cells IL-2 rest
0.0
NCI-H292 IL-13
0.0


Two Way MLR 3 day
0.0
NCI-H292 IFN gamma
0.0


Two Way MLR 5 day
0.0
HPAEC none
0.0


Two Way MLR 7 day
0.0
HPAEC TNF alpha + IL-
0.0




1beta


PBMC rest
0.0
Lung fibroblast none
0.0


PBMC PWM
0.0
Lung fibroblast TNF
0.0




alpha + IL-1beta


PBMC PHA-L
0.0
Lung fibroblast IL-4
0.0


Ramos (B cell) none
0.0
Lung fibroblast IL-9
0.0


Ramos (B cell)
0.0
Lung fibroblast IL-13
0.0


ionomycin


B lymphocytes PWM
0.0
Lung fibroblast IFN
0.0




gamma


B lymphocytes CD40L
0.0
Dermal fibroblast
0.0


and IL-4

CCD1070 rest


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0




CCD1070 TNF alpha


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
0.0
Dermal fibroblast IFN
0.0




gamma


Dendritic cells LPS
0.0
Dermal fibroblast IL-4
0.0


Dendritic cells anti-
0.0
IBD Colitis 2
0.0


CD40


Monocytes rest
0.0
IBD Crohn's
0.0


Monocytes LPS
0.0
Colon
12.7


Macrophages rest
0.0
Lung
15.2


Macrophages LPS
0.0
Thymus
100.0


HUVEC none
0.0
Kidney
73.2


HUVEC starved
0.0










[1510] CNS_neurodegeneration_v1.0 Summary: Ag3355 This panel confirms the expression of CG58183-01 gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.


[1511] General_screening_panel_v1.4 Summary: Ag3355 Highest expression of CG58183-01 gene is detected in fetal brain (Ct=29.2). In addition, this gene is expressed at high levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord (CTs=29-32). Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[1512] This gene codes for N-methyl-D-aspartate (NMDA) receptor 3A protein. In cats and rhodent models competitive NMDA receptor antagonists, such as D-(E)-4-(3-phosphonoprop-2-enyl)piperazine-2-carboxylic acid, which act at the neurotransmitter recognition site were shown to be effective in reducing ischaemic brain damage when administered prior to the onset of an ischaemic episode (Ref. 1). Therefore, therapeutic modulation of the activity of the protein encoded by this gene may be beneficial in the treatment of ischaemic brain.


[1513] Among tissues with metabolic or endocrine function, this gene is expressed at low levels in pancreas, heart, and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.


[1514] Furthermore, low to moderate expression of this gene is detected in lung cancer, and CNS3 cancer cell lines. Therefore, therapeutic modulation of the activity of this gene or its protein product, through the use of small molecule drugs, protein therapeutics or antibodies, might be beneficial in the treatment of lung cancer or CNS cancer.



REFERENCES

[1515] 1. McCulloch J. (1991) Ischaemic brain damage—prevention with competitive and non-comnpetitive antagonists of N-methyl-D-aspartate receptors. Arzneimittelforschung 41(3A):319-24.


[1516] Panel 4D Summary: Ag3355 Expression of the CG58183-01 gene is limited to a few samples, with highest expression in the thymus (CT=33.5). Thus, expression of this gene may be useful as a marker of thymic tissue. Low, but significant levels of expression are also seen in the kidney, in TNF-alpha and IL-1 beta treated astrocytes and in the PMA/ionomycin treated basophil cell line KU-812. Thus, this gene product may be involved in the normal homeostasis of this tissue. Therefore, agonistic antibodies or protein therapeutics may be important in the treatment of inflammatory or autoimmune diseases that affect the kidney, including lupus and glomerulonephritis. In addition, the expression of this transcript in astrocytes treated with TNF-a and IL-1 indicates that therapeutics designed against the protein encoded by this gene may be useful for the treatment of inflammatory CNS diseases such as multiple sclerosis.


[1517] AK. CG59315-01: connexin


[1518] Expression of gene CG59315-01 was assessed using the primer-probe set Ag3542, described in Table AKA. Results of the RTQ-PCR runs are shown in Tables AKB and AKC.


[1519] Table AKA. Probe Name Ag3542
810TABLE AKAProbe Name Ag3542StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-ggacacctcccaacctagatc-3′211024508ProbeTET-5′-tacctgtcttccttccttgaggctgg-3′-TAMRA261046509Reverse5′-ttgcattcttgtgtccatgag-3′211081510


[1520]

811





TABLE AKB










General_screening_panel_v1.4











Rel. Exp. (%)

Rel. Exp. (%)



Ag3542, Run

Ag3542, Run


Tissue Name
217049297
Tissue Name
217049297













Adipose
17.3
Renal ca. TK-10
6.8


Melanoma*
0.4
Bladder
2.5


Hs688(A).T


Melanoma*
1.0
Gastric ca. (liver met.)
13.1


Hs688(B).T

NCI-N87


Melanoma* M14
12.2
Gastric ca. KATO III
12.2


Melanoma*
0.0
Colon ca. SW-948
3.8


LOXIMVI


Melanoma* SK-
0.7
Colon ca. SW480
39.0


MEL-5


Squamous cell
2.0
Colon ca.* (SW480
6.7


carcinoma SCC-4

met) SW620


Testis Pool
0.3
Colon ca. HT29
2.3


Prostate ca.* (bone
0.0
Colon ca. HCT-116
17.7


met) PC-3


Prostate Pool
0.0
Colon ca. CaCo-2
2.8


Placenta
1.2
Colon cancer tissue
1.6


Uterus Pool
0.0
Colon ca. SW1116
0.3


Ovarian ca.
6.3
Colon ca. Colo-205
0.3


OVCAR-3


Ovarian ca. SK-
2.5
Colon ca. SW-48
0.0


OV-3


Ovarian ca.
0.0
Colon Pool
1.7


OVCAR-4


Ovarian ca.
25.0
Small Intestine Pool
6.3


OVCAR-5


Ovarian ca.
6.4
Stomach Pool
5.4


IGROV-1


Ovarian ca.
0.0
Bone Marrow Pool
3.1


OVCAR-8


Ovary
0.6
Fetal Heart
1.7


Breast ca. MCF-7
12.9
Heart Pool
1.5


Breast ca. MDA-
5.0
Lymph Node Pool
3.6


MB-231


Breast ca. BT 549
8.7
Fetal Skeletal Muscle
0.0


Breast ca. T47D
100.0
Skeletal Muscle Pool
6.1


Breast ca. MDA-N
2.7
Spleen Pool
5.8


Breast Pool
4.9
Thymus Pool
3.0


Trachea
9.3
CNS cancer
1.0




(glio/astro) U87-MG


Lung
0.0
CNS cancer
13.7




(glio/astro) U-118-MG


Fetal Lung
3.2
CNS cancer
35.4




(neuro; met) SK-N-AS


Lung ca. NCI-N417
1.2
CNS cancer (astro) SF-
4.9




539


Lung ca. LX-1
11.7
CNS cancer (astro)
2.7




SNB-75


Lung ca. NCI-H146
2.9
CNS cancer (glio)
1.4




SNB-19


Lung ca. SHP-77
8.1
CNS cancer (glio) SF-
12.5




295


Lung ca. A549
10.8
Brain (Amygdala) Pool
0.4


Lung ca. NCI-H526
2.1
Brain (cerebellum)
13.6


Lung ca. NCI-H23
8.1
Brain (fetal)
6.9


Lung ca. NCI-H460
0.8
Brain (Hippocampus)
1.5




Pool


Lung ca. HOP-62
10.2
Cerebral Cortex Pool
0.0


Lung ca. NCI-H522
4.9
Brain (Substantia
0.2




nigra) Pool


Liver
0.0
Brain (Thalamus) Pool
1.2


Fetal Liver
1.2
Brain (whole)
0.0


Liver ca. HepG2
0.0
Spinal Cord Pool
0.4


Kidney Pool
3.1
Adrenal Gland
2.0


Fetal Kidney
0.0
Pituitary gland Pool
1.8


Renal ca. 786-0
6.3
Salivary Gland
3.2


Renal ca. A498
0.0
Thyroid (female)
3.8


Renal ca. ACHN
12.1
Pancreatic ca.
0.0




CAPAN2


Renal ca. UO-31
3.2
Pancreas Pool
4.2










[1521]

812





TABLE AKC










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3542, Run

Ag3542, Run


Tissue Name
166453844
Tissue Name
166453844













Secondary Th1 act
3.9
HUVEC IL-1beta
0.0


Secondary Th2 act
5.4
HUVEC IFN gamma
2.4


Secondary Tr1 act
3.8
HUVEC TNF alpha +
0.4




IFN gamma


Secondary Th1 rest
33.0
HUVEC TNF alpha +
0.0




IL4


Secondary Th2 rest
5.3
HUVEC IL-11
1.4


Secondary Tr1 rest
14.8
Lung Microvascular EC
3.1




none


Primary Th1 act
6.1
Lung Microvascular EC
1.9




TNF alpha + IL-1beta


Primary Th2 act
0.6
Microvascular Dermal
1.9




EC none


Primary Tr1 act
5.5
Microsvasular Dermal
0.0




EC TNF alpha + IL-1beta


Primary Th1 rest
84.7
Bronchial epithelium
2.7




CCD1070 TNF alpha


EOL-1 dbcAMP
11.7
Dermal fibroblast
0.0


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
6.3
Dermal fibroblast IFN
0.3




gamma


Dendritic cells LPS
1.4
Dermal fibroblast IL-4
1.4


Dendritic cells anti-
2.3
IBD Colitis 2
4.0


CD40


Monocytes rest
53.2
IBD Crohn's
3.2


Monocytes LPS
19.2
Colon
100.0


Macrophages rest
0.6
Lung
11.1


Macrophages LPS
0.0
Thymus
2.7


HUVEC none
5.4
Kidney
7.7


HUVEC starved
4.3










[1522] CNS_neurodegeneration_v1.0 Summary: Ag3542 Expression of the CG59315-01 gene is low/undetectable in all the samples on this panel. (CTs>35). (Data not shown.)


[1523] General_screening_panel_v1.4 Summary: Ag3542 Expression of the CG59315-01 gene is highest in a breast cancer cell line (CT=31.3). Furthermore, there is significant expression in a cluster of cell lines derived from brain cancer, colon cancer and ovarian cancer. Therefore, expression of this gene could be used to differentiate between these samples and other samples on this panel and as a marker to detect the presence of colon, brain, ovarian, and breast cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of colon, brain, ovarian, and breast cancers.


[1524] Low but significant levels of expression are also seen in the cerebellum. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.


[1525] Among metabolic tissues, this gene is expressed at low levels in adipose. Therefore, this gene product may be useful in the treatment of obesity.


[1526] Panel 4D Summary: Ag3542 Expression of the CG59315-01 gene is highest in the normal colon (CT=30). Furthermore, expression is undetectable in colon samples from Crohn's and colitis patients. Thus, expression of this gene could be used to differentiate between normal and inflammed colon. This gene encodes a connexin homolog, a gap junction protein involved in intercellular communication.


[1527] The expression of this connexin-like protein in several of the resting and activated T lymphocyte preparations and in resting monocytes suggests that small molecule antagonists or therapeutic antibodies that block its function may also be useful in the treatment of a number of inflammatory and autoimmune diseases in which T cells and monocytes play a pivotal role. These include, but are not limited to, Crohn's disease, ulcerative colitis, multiple sclerosis, chronic obstructive pulmonary disease, asthma, emphysema, rheumatoid arthritis, lupus erythematosus, or psoriasis.



REFERENCES

[1528] 1. Kwak B R, Mulhaupt F, Veillard N, Gros D B, Mach F. Altered pattern of vascular connexin expression in atherosclerotic plaques. Arterioscler Thromb Vasc Biol Feb. 1, 2002;22(2):225-30


[1529] AL. CG59203-01: Lysozyme C-Like Protein


[1530] Expression of gene CG59203-01 was assessed using the primer-probe set Ag3392, described in Table ALA. Results of the RTQ-PCR runs are shown in Tables ALB and ALC.


[1531] Table ALA. Probe Name Ag3392
813TABLE ALAProbe Name Ag3392StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-tgtgaggtttcctaaactggaa-3′22540511ProbeTET-5′-ctttgcagcaacgccctagggttt-3′-TAMRA24576512Reverse5′-tgacacaggcatttggacat-3′20607513


[1532]

814





TABLE ALB










General_screening_panel_v1.4











Rel. Exp. (%)

Rel. Exp. (%)



Ag3392, Run

Ag3392, Run


Tissue Name
216821373
Tissue Name
216821373













Adipose
0.0
Renal ca. TK-10
2.7


Melanoma*
0.0
Bladder
0.0


Hs688(A).T


Melanoma*
0.0
Gastric ca. (liver met.)
0.7


Hs688(B).T

NCI-N87


Melanoma* M14
1.2
Gastric ca. KATO III
0.4


Melanoma*
0.0
Colon ca. SW-948
0.6


LOXIMVI


Melanoma* SK-
0.0
Colon ca. SW480
2.0


MEL-5


Squamous cell
0.0
Colon ca.* (SW480
4.7


carcinoma SCC-4

met) SW620


Testis Pool
100.0
Colon ca. HT29
0.0


Prostate ca.* (bone
0.0
Colon ca. HCT-116
0.0


met) PC-3


Prostate Pool
0.0
Colon ca. CaCo-2
1.2


Placenta
0.7
Colon cancer tissue
0.0


Uterus Pool
0.0
Colon ca. SW1116
0.0


Ovarian ca.
0.4
Colon ca. Colo-205
11.6


OVCAR-3


Ovarian ca. SK-
1.0
Colon ca. SW-48
2.2


OV-3


Ovarian ca.
0.0
Colon Pool
1.1


OVCAR-4


Ovarian ca.
0.0
Small Intestine Pool
0.4


OVCAR-5


Ovarian ca.
0.0
Stomach Pool
0.0


IGROV-1


Ovarian ca.
0.0
Bone Marrow Pool
1.3


OVCAR-8


Ovary
0.0
Fetal Heart
0.0


Breast ca. MCF-7
15.2
Heart Pool
1.1


Breast ca. MDA-
0.0
Lymph Node Pool
0.0


MB-231


Breast ca. BT 549
1.7
Fetal Skeletal Muscle
0.0


Breast ca. T47D
0.0
Skeletal Muscle Pool
0.5


Breast ca. MDA-N
0.0
Spleen Pool
0.0


Breast Pool
0.0
Thymus Pool
0.9


Trachea
1.1
CNS cancer
1.4




(glio/astro) U87-MG


Lung
0.0
CNS cancer
0.5




(glio/astro) U-118-MG


Fetal Lung
0.8
CNS cancer
0.0




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.0
CNS cancer (astro) SF-
0.0




539


Lung ca. LX-1
5.4
CNS cancer (astro)
6.1




SNB-75


Lung ca. NCI-H146
0.0
CNS cancer (glio)
0.0




SNB-19


Lung ca. SHP-77
0.0
CNS cancer (glio) SF-
0.0




295


Lung ca. A549
3.1
Brain (Amygdala) Pool
0.0


Lung ca. NCI-H526
0.0
Brain (cerebellum)
0.0


Lung ca. NCI-H23
0.9
Brain (fetal)
0.0


Lung ca. NCI-H460
1.1
Brain (Hippocampus)
0.0




Pool


Lung ca. HOP-62
0.0
Cerebral Cortex Pool
0.5


Lung ca. NCI-H522
0.0
Brain (Substantia
0.0




nigra) Pool


Liver
1.5
Brain (Thalamus) Pool
0.9


Fetal Liver
1.2
Brain (whole)
0.0


Liver ca. HepG2
18.3
Spinal Cord Pool
0.0


Kidney Pool
1.6
Adrenal Gland
0.0


Fetal Kidney
0.0
Pituitary gland Pool
0.0


Renal ca. 786-0
0.3
Salivary Gland
0.0


Renal ca. A498
0.0
Thyroid (female)
0.0


Renal ca. ACHN
0.0
Pancreatic ca.
0.0




CAPAN2


Renal ca. UO-31
0.0
Pancreas Pool
0.0










[1533]

815





TABLE ALC










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3392, Run

Ag3392, Run


Tissue Name
165296470
Tissue Name
165296470













Secondary Th1 act
0.0
HUVEC IL-1beta
0.0


Secondary Th2 act
36.9
HUVEC IFN gamma
0.0


Secondary Tr1 act
0.0
HUVEC TNF alpha +
0.0




IFN gamma


Secondary Th1 rest
0.0
HUVEC TNF alpha +
0.0




IL4


Secondary Th2 rest
0.0
HUVEC IL-11
0.0


Secondary Tr1 rest
0.0
Lung Microvascular EC
0.0




none


Primary Th1 act
0.0
Lung Microvascular EC
0.0




TNF alpha + IL-1beta


Primary Th2 act
0.0
Microvascular Dermal
0.0




EC none


Primary Tr1 act
0.0
Microsvasular Dermal
0.0




EC TNF alpha + IL-1beta


Primary Th1 rest
0.0
Bronchial epithelium
0.0




TNF alpha + IL-1beta


Primary Th2 rest
0.0
Small airway epithelium
0.0




none


Primary Tr1 rest
0.0
Small airway epithelium
0.0




TNF alpha + IL-1beta


CD45RA CD4
0.0
Coronery artery SMC rest
0.0


lymphocyte act


CD45RO CD4
0.0
Coronery artery SMC
0.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
0.0
Astrocytes rest
0.0


Secondary CD8
0.0
Astrocytes TNF alpha +
0.0


lymphocyte rest

IL-1beta


Secondary CD8
0.0
KU-812 (Basophil) rest
0.0


lymphocyte act


CD4 lymphocyte none
0.0
KU-812 (Basophil)
0.0




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
0.0
CCD1106
0.0


CD95 CH11

(Keratinocytes) none


LAK cells rest
0.0
CCD1106
0.0




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
0.0
Liver cirrhosis
100.0


LAK cells IL-2 + IL-12
0.0
Lupus kidney
0.0


LAK cells IL-2 + IFN
0.0
NCI-H292 none
0.0


gamma


LAK cells IL-2 + IL-18
0.0
NCI-H292 IL-4
0.0


LAK cells
16.8
NCI-H292 IL-9
0.0


PMA/ionomycin


NK Cells IL-2 rest
0.0
NCI-H292 IL-13
0.0


Two Way MLR 3 day
0.0
NCI-H292 IFN gamma
0.0


Two Way MLR 5 day
0.0
HPAEC none
0.0


Two Way MLR 7 day
0.0
HPAEC TNF alpha + IL-
0.0




1beta


PBMC rest
0.0
Lung fibroblast none
0.0


PBMC PWM
11.1
Lung fibroblast TNF
0.0




alpha + IL-1beta


PBMC PHA-L
0.0
Lung fibroblast IL-4
0.0


Ramos (B cell) none
0.0
Lung fibroblast IL-9
0.0


Ramos (B cell)
0.0
Lung fibroblast IL-13
0.0


ionomycin


B lymphocytes PWM
26.8
Lung fibroblast IFN
0.0




gamma


B lymphocytes CD40L
0.0
Dermal fibroblast
0.0


and IL-4

CCD1070 rest


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0




CCD1070 TNF alpha


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
0.0
Dermal fibroblast IFN
0.0




gamma


Dendritic cells LPS
0.0
Dermal fibroblast IL-4
0.0


Dendritic cells anti-
0.0
IBD Colitis 2
0.0


CD40


Monocytes rest
0.0
IBD Crohn's
0.0


Monocytes LPS
0.0
Colon
0.0


Macropages rest
0.0
Lung
0.0


Macrophages LPS
0.0
Thymus
0.0


HUVEC none
0.0
Kidney
0.0


HUVEC starved
0.0










[1534] CNS_neurodegeneration_v1.0 Summary: Ag3392 Expression of the CG59203-01 gene is low/undetectable in all samples on this panel (CTs>35). (Data not shown.)


[1535] General_screening_panel_v1.4 Summary: Ag3392 Highest expression of the CG59203-01 gene is seen in the testis. Thus, expression of this gene could be used as a marker of testicular tissue. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in treating infertility or hypogonadism.


[1536] Panel 4D Summary: Ag3392 Significant expression of this gene is detected in a liver cirrhosis sample (CT=33.8). Furthermore, expression of this gene is not detected in normal liver in Panel 1.3D, suggesting that its expression is unique to liver cirrhosis. Therefore, therapeutic modulation of the expression or function of this gene may reduce or inhibit fibrosis that occurs in liver cirrhosis. In addition, expression of this gene could also be used for the diagnosis of liver cirrhosis.


[1537] AM. CG58662-01: Cytoplasmic Protein


[1538] Expression of gene CG58662-01 was assessed using the primer-probe set Ag3387, described in Table AMA. Results of the RTQ-PCR runs are shown in Tables AMB, AMC and AMD.


[1539] Table AMA. Probe Name Ag3387
816TABLE AMAProbe Name Ag3387StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-aacctgcactcctccatga-3′19504514ProbeTET-5′-agaccccagcagggtatcctctgag-3′-TAMRA25532515Reverse5′-ctctgtcagtgcccacatct-3′20564516


[1540]

817





TABLE AMB










CNS_neurodegeneration_v1.0













Rel. Exp.





(%)



Rel. Exp. (%)

Ag3387,



Ag3387, Run

Run


Tissue Name
210155038
Tissue Name
210155038













AD 1 Hippo
15.7
Control (Path) 3
7.3




Temporal Ctx


AD 2 Hippo
34.6
Control (Path) 4
42.0




Temporal Ctx


AD 3 Hippo
5.5
AD 1 Occipital Ctx
17.9


AD 4 Hippo
9.7
AD 2 Occipital Ctx
0.0




(Missing)


AD 5 Hippo
95.3
AD 3 Occipital Ctx
5.4


AD 6 Hippo
33.9
AD 4 Occipital Ctx
19.6


Control 2 Hippo
41.5
AD 5 Occipital Ctx
61.1


Control 4 Hippo
9.0
AD 6 Occipital Ctx
19.5


Control (Path) 3
6.7
Control 1 Occipital
5.8


Hippo

Ctx


AD 1 Temporal
11.2
Control 2 Occipital
83.5


Ctx

Ctx


AD 2 Temporal
37.6
Control 3 Occipital
19.3


Ctx

Ctx


AD 3 Temporal
4.0
Control 4 Occipital
5.0


Ctx

Ctx


AD 4 Temporal
21.5
Control (Path) 1
88.9


Ctx

Occipital Ctx


AD 5 Inf Temporal
100.0
Control (Path) 2
13.4


Ctx

Occipital Ctx


AD 5 Sup
37.9
Control (Path) 3
5.8


Temporal Ctx

Occipital Ctx


AD 6 Inf Temporal
35.6
Control (Path) 4
24.3


Ctx

Occipital Ctx


AD 6 Sup
39.2
Control 1 Parietal
9.4


Temporal Ctx

Ctx


Control 1
6.7
Control 2 Parietal
44.4


Temporal Ctx

Ctx


Control 2
65.5
Control 3 Parietal
28.5


Temporal Ctx

Ctx


Control 3
19.3
Control (Path) 1
90.8


Temporal Ctx

Parietal Ctx


Control 3
11.4
Control (Path) 2
25.7


Temporal Ctx

Parietal Ctx


Control (Path) 1
83.5
Control (Path) 3
5.6


Temporal Ctx

Parietal Ctx


Control (Path) 2
56.6
Control (Path) 4
56.6


Temporal Ctx

Parietal Ctx










[1541]

818





TABLE AMC










General_screening_panel_v1.4











Rel. Exp. (%)

Rel. Exp. (%)



Ag3387,

Ag3387,


Tissue Name
Run 217043912
Tissue Name
Run 217043912













Adipose
8.2
Renal ca. TK-10
66.4


Melanoma* Hs688(A).T
30.6
Bladder
11.2


Melanoma*
34.6
Gastric ca. (liver met.)
15.3


Hs688(B).T

NCI-N87


Melanoma* M14
27.0
Gastric ca. KATO III
20.6


Melanoma* LOXIMVI
17.6
Colon ca. SW-948
1.1


Melanoma* SK-
25.3
Colon ca. SW480
33.0


MEL-5


Squamous cell
5.7
Colon ca.* (SW480
29.9


carcinoma SCC-4

met) SW620


Testis Pool
17.8
Colon ca. HT29
8.8


Prostate ca.* (bone
27.7
Colon ca. HCT-116
15.4


met) PC-3


Prostate Pool
16.0
Colon ca. CaCo-2
13.1


Placenta
11.0
Colon cancer tissue
13.8


Uterus Pool
1.7
Colon ca. SW1116
7.9


Ovarian ca.
17.0
Colon ca. Colo-205
4.4


OVCAR-3


Ovarian ca. SK-
11.3
Colon ca. SW-48
9.3


OV-3


Ovarian ca.
7.1
Colon Pool
20.4


OVCAR-4


Ovarian ca.
37.4
Small Intestine Pool
12.5


OVCAR-5


Ovarian ca.
23.7
Stomach Pool
12.1


IGROV-1


Ovarian ca.
16.8
Bone Marrow Pool
4.3


OVCAR-8


Ovary
20.0
Fetal Heart
18.7


Breast ca. MCF-7
5.6
Heart Pool
12.3


Breast ca. MDA-
41.5
Lymph Node Pool
18.9


MB-231


Breast ca. BT 549
55.1
Fetal Skeletal Muscle
8.9


Breast ca. T47D
63.3
Skeletal Muscle Pool
23.2


Breast ca. MDA-N
23.5
Spleen Pool
10.8


Breast Pool
25.5
Thymus Pool
18.0


Trachea
13.6
CNS cancer
62.4




(glio/astro) U87-MG


Lung
5.3
CNS cancer
12.5




(glio/astro) U-118-MG


Fetal Lung
32.5
CNS cancer
8.1




(neuro; met) SK-N-AS


Lung ca. NCI-N417
6.2
CNS cancer (astro) SF-
17.3




539


Lung ca. LX-1
33.7
CNS cancer (astro)
27.2




SNB-75


Lung ca. NCI-H146
10.0
CNS cancer (glio)
25.9




SNB-19


Lung ca. SHP-77
39.2
CNS cancer (glio) SF-
54.0




295


Lung ca. A549
43.8
Brain (Amygdala) Pool
47.6


Lung ca. NCI-H526
6.5
Brain (cerebellum)
90.1


Lung ca. NCI-H23
44.8
Brain (fetal)
56.6


Lung ca. NCI-H460
23.8
Brain (Hippocampus) Pool
45.7


Lung ca. HOP-62
53.6
Cerebral Cortex Pool
60.3


Lung ca. NCI-H522
100.0
Brain (Substantia
61.6




nigra) Pool


Liver
4.4
Brain (Thalamus) Pool
75.8


Fetal Liver
17.0
Brain (whole)
63.3


Liver ca. HepG2
33.9
Spinal Cord Pool
24.1


Kidney Pool
37.1
Adrenal Gland
23.5


Fetal Kidney
16.4
Pituitary gland Pool
3.9


Renal ca. 786-0
14.8
Salivary Gland
9.9


Renal ca. A498
7.5
Thyroid (female)
29.1


Renal ca. ACHN
26.2
Pancreatic ca.
39.8




CAPAN2


Renal ca. UO-31
81.8
Pancreas Pool
49.3










[1542]

819





TABLE AMD










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3387, Run

Ag3387, Run


Tissue Name
165296475
Tissue Name
165296475













Secondary Th1 act
24.1
HUVEC IL-1beta
12.1


Secondary Th2 act
29.9
HUVEC IFN gamma
27.0


Secondary Tr1 act
26.2
HUVEC TNF alpha +
19.1




IFN gamma


Secondary Th1 rest
18.9
HUVEC TNF alpha +
16.0




IL4


Secondary Th2 rest
22.8
HUVEC IL-11
16.4


Secondary Tr1 rest
28.1
Lung Microvascular EC
36.6




none


Primary Th1 act
12.4
Lung Microvascular EC
27.2




TNF alpha + IL-1beta


Primary Th2 act
20.9
Microvascular Dermal
43.5




EC none


Primary Tr1 act
25.7
Microsvasular Dermal
23.2




EC TNF alpha + IL-1beta


Primary Th1 rest
46.0
Bronchial epithelium
18.0




TNF alpha + IL1beta


Primary Th2 rest
36.1
Small airway epithelium
3.9




none


Primary Tr1 rest
37.6
Small airway epithelium
33.2




TNF alpha + IL-1beta


CD45RA CD4
5.7
Coronery artery SMC rest
19.6


lymphocyte act


CD45RO CD4
19.9
Coronery artery SMC
12.7


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
16.2
Astrocytes rest
27.9


Secondary CD8
11.3
Astrocytes TNF alpha +
21.8


lymphocyte rest

IL-1beta


Secondary CD8
12.3
KU-812 (Basophil) rest
7.6


lymphocyte act


CD4 lymphocyte none
5.7
KU-812 (Basophil)
22.1




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
12.2
CCD1106
12.0


CD95 CH11

(Keratinocytes) none


LAK cells rest
19.2
CCD1106
19.3




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
25.9
Liver cirrhosis
9.4


LAK cells IL-2 + IL-12
10.2
Lupus kidney
3.2


LAK cells IL-2 + IFN
26.4
NCI-H292 none
62.0


gamma


LAK cells IL-2 + IL-18
21.2
NCI-H292 IL-4
71.2


LAK cells
4.2
NCI-H292 IL-9
52.5


PMA/ionomycin


NK Cells IL-2 rest
21.2
NCI-H292 IL-13
24.8


Two Way MLR 3 day
30.6
NCI-H292 IFN gamma
33.7


Two Way MLR 5 day
26.2
HPAEC none
27.7


Two Way MLR 7 day
16.8
HPAEC TNF alpha + IL-
12.6




1beta


PBMC rest
10.7
Lung fibroblast none
25.3


PBMC PWM
21.3
Lung fibroblast TNF
12.1




alpha + IL-1beta


PBMC PHA-L
25.5
Lung fibroblast IL-4
48.0


Ramos (B cell) none
18.4
Lung fibroblast IL-9
34.6


Ramos (B cell)
68.3
Lung fibroblast IL-13
51.1


ionomycin


B lymphocytes PWM
54.0
Lung fibroblast IFN
63.3




gamma


B lymphocytes CD40L
0.0
Dermal fibroblast
20.4


and IL-4

CCD1070 rest


EOL-1 dbcAMP
18.4
Dermal fibroblast
74.2




CCD1070 TNF alpha


EOL-1 dbcAMP
3.1
Dermal fibroblast
4.6


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
28.1
Dermal fibroblast IFN
10.1




gamma


Dendritic cells LPS
29.7
Dermal fibroblast IL-4
23.8


Dendritic cells anti-
19.6
IBD Colitis 2
1.4


CD40


Monocytes rest
17.2
IBD Crohn's
2.4


Monocytes LPS
1.6
Colon
21.8


Macrophages rest
30.8
Lung
16.6


Macrophages LPS
17.4
Thymus
100.0


HUVEC none
22.8
Kidney
48.0


HUVEC starved
28.5










[1543] CNS_neurodegeneration_v1.0 Summary: Ag3387 This panel does not show differential expression of the CG58662-01 gene in Alzheimer's disease. However, this expression profile confirms the presence of this gene in the brain. Please see Panel 1.3D for discussion of utility of this gene in the central nervous system.


[1544] General_screening_panel_v1.4 Summary: Ag3387 Expression of the CG58662-01 gene is ubiquitous in this panel, with highest expression in a lung cancer cell line (CT=29.5). In addition, this gene is expressed at higher levels in kidney cancer cell lines when compared to normal kidney expression. Thus, expression of this gene could be used to differentiate these samples from other samples and as a marker for these cancers. Furthermore, therapeutic modulation of the expression of function of this gene may be effective in the treatment of lung and kidney cancer.


[1545] Among metabolic tissues this gene is expressed at moderate to low levels in adipose, adrenal gland, pancreas, pituitary, and adult and fetal skeletal muscle, heart and liver. This widespread expression among these tissues suggests that this gene plays a role in normal metabolic and neuroendocrine function and that disregulated expression of this gene may contribute to neuroendocrine diseases or metabolic disorders, such as obesity and diabetes.


[1546] In addition, this gene is expressed at moderate to low levels in all CNS regions examinded and may be a small molecule target for the treatment of neurologic diseases, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.


[1547] Panel 4D Summary: Ag3387 The CG58662-01 gene is expressed at high to moderate levels in a wide range of cell types of significance in the immune response in health and disease, with highest expression in the thymus (CT=31). In addition, expression is seen in members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.5 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.


[1548] AN. CG59371-01: Novel Cytoplasmic Protein


[1549] Expression of gene CG59371-01 was assessed using the primer-probe set Ag3558, described in Table ANA. Results of the RTQ-PCR runs are shown in Tables ANB, ANC, AND and ANE.


[1550] Table ANA. Probe Name Ag3558
820TABLE ANAProbe Name Ag3558SEQStartIDPrimersSequencesLengthPositionNO:Forward5′-cttgaggctgagaaggagaag-3′21208517ProbeTET-5′-tgcttatcaactcacagagaaggaca-3′-TAMRA26231518Reverse5′-gttggtctctcagtcgctgta-3′21263519


[1551]

821





TABLE ANB










General_screening_panel_v1.4











Rel. Exp. (%)

Rel. Exp. (%)



Ag3558, Run

Ag3558, Run


Tissue Name
213391281
Tissue Name
213391281













Adipose
0.4
Renal ca. TK-10
14.3


Melanoma* Hs688(A).T
1.9
Bladder
5.7


Melanoma*
2.2
Gastric ca. (liver met.)
6.4


Hs688(B).T

NCI-N87


Melanoma* M14
41.5
Gastric ca. KATO III
82.9


Melanoma* LOXIMVI
30.1
Colon ca. SW-948
14.8


Melanoma* SK-MEL-5
23.8
Colon ca. SW480
81.2


Squamous cell
34.6
Colon ca.* (SW480
24.0


carcinoma SCC-4

met) SW620


Testis Pool
7.6
Colon ca. HT29
20.6


Prostate ca.* (bone met) PC-3
9.7
Colon ca. HCT-116
61.6


Prostate Pool
0.1
Colon ca. CaCo-2
17.7


Placenta
0.3
Colon cancer tissue
7.7


Uterus Pool
0.1
Colon ca. SW1116
6.9


Ovarian ca.
15.3
Colon ca. Colo-205
3.2


OVCAR-3


Ovarian ca. SK-OV-3
62.0
Colon ca. SW-48
9.3


Ovarian ca. OVCAR-4
27.5
Colon Pool
0.3


Ovarian ca.
14.4
Small Intestine Pool
0.1


OVCAR-5


Ovarian ca.
5.8
Stomach Pool
2.0


IGROV-1


Ovarian ca.
2.5
Bone Marrow Pool
0.3


OVCAR-8


Ovary
0.2
Fetal Heart
3.3


Breast ca. MCF-7
15.5
Heart Pool
0.0


Breast ca. MDA-
100.0
Lymph Node Pool
0.5


MB-231


Breast ca. BT 549
72.7
Fetal Skeletal Muscle
0.7


Breast ca. T47D
17.1
Skeletal Muscle Pool
0.0


Breast ca. MDA-N
13.5
Spleen Pool
0.8


Breast Pool
0.2
Thymus Pool
7.2


Trachea
0.4
CNS cancer
17.6




(glio/astro) U87-MG


Lung
0.0
CNS cancer
61.6




(glio/astro) U-118-MG


Fetal Lung
2.5
CNS cancer
14.9




(neuro; met) SK-N-AS


Lung ca. NCI-N417
5.4
CNS cancer (astro) SF-
21.6




539


Lung ca. LX-1
27.2
CNS cancer (astro)
30.4




SNB-75


Lung ca. NCI-H146
15.2
CNS cancer (glio)
4.6




SNB-19


Lung ca. SHP-77
42.0
CNS cancer (glio) SF-
0.8




295


Lung ca. A549
28.5
Brain (Amygdala) Pool
0.1


Lung ca. NCI-H526
6.4
Brain (cerebellum)
0.0


Lung ca. NCI-H23
21.3
Brain (fetal)
1.1


Lung ca. NCI-H460
0.7
Brain (Hippocampus) Pool
0.2


Lung ca. HOP-62
4.7
Cerebral Cortex Pool
0.1


Lung ca. NCI-H522
23.8
Brain (Substantia
0.1




nigra) Pool


Liver
0.0
Brain (Thalamus) Pool
0.0


Fetal Liver
0.8
Brain (whole)
0.0


Liver ca. HepG2
7.7
Spinal Cord Pool
0.1


Kidney Pool
0.1
Adrenal Gland
0.2


Fetal Kidney
4.1
Pituitary gland Pool
0.0


Renal ca. 786-0
52.5
Salivary Gland
0.0


Renal ca. A498
6.5
Thyroid (female)
0.2


Renal ca. ACHN
14.0
Pancreatic ca. CAPAN2
43.2


Renal ca. UO-31
20.2
Pancreas Pool
0.9










[1552]

822





TABLE ANC










General_screening_panel_v.1.5











Rel. Exp. (%)

Rel. Exp. (%)



Ag3558, Run

Ag3558, Run


Tissue Name
248592792
Tissue Name
248592792













Adipose
0.4
Renal ca. TK-10
16.6


Melanoma* Hs688(A).T
2.0
Bladder
3.3


Melanoma*
3.1
Gastric ca. (liver met.)
6.7


Hs688(B).T

NCI-N87


Melanoma* M14
34.9
Gastric ca. KATO III
93.3


Melanoma* LOXIMVI
26.4
Colon ca. SW-948
13.0


Melanoma* SK-MEL-5
29.5
Colon ca. SW480
76.3


Squamous cell
33.0
Colon ca.* (SW480
25.5


carcinoma SCC-4

met) SW620


Testis Pool
7.2
Colon ca. HT29
18.8


Prostate ca.* (bone met) PC-3
10.3
Colon ca. HCT-116
55.5


Prostate Pool
0.1
Colon ca. CaCo-2
23.5


Placenta
0.1
Colon cancer tissue
5.0


Uterus Pool
0.2
Colon ca. SW1116
4.6


Ovarian ca.
29.5
Colon ca. Colo-205
5.6


OVCAR-3


Ovarian ca. SK-
40.6
Colon ca. SW-48
6.8


OV-3


Ovarian ca.
29.5
Colon Pool
0.2


OVCAR-4


Ovarian ca.
11.7
Small Intestine Pool
0.2


OVCAR-5


Ovarian ca.
4.6
Stomach Pool
0.2


IGROV-1


Ovarian ca.
5.2
Bone Marrow Pool
0.2


OVCAR-8


Ovary
0.2
Fetal Heart
2.0


Breast ca. MCF-7
18.0
Heart Pool
0.0


Breast ca. MDA-
85.3
Lymph Node Pool
0.5


MB-231


Breast ca. BT 549
100.0
Fetal Skeletal Muscle
0.8


Breast ca. T47D
23.3
Skeletal Muscle Pool
0.0


Breast ca. MDA-N
20.2
Spleen Pool
1.0


Breast Pool
0.3
Thymus Pool
3.7


Trachea
0.4
CNS cancer
15.4




(glio/astro) U87-MG


Lung
0.0
CNS cancer
64.6




(glio/astro) U-118-MG


Fetal Lung
3.5
CNS cancer
24.7




(neuro; met) SK-N-AS


Lung ca. NCI-N417
5.0
CNS cancer (astro) SF-
21.6




539


Lung ca. LX-1
32.1
CNS cancer (astro)
30.4




SNB-75


Lung ca. NCI-H146
13.6
CNS cancer (glio)
4.8




SNB-19


Lung ca. SHP-77
34.9
CNS cancer (glio) SF-
3.3




295


Lung ca. A549
35.4
Brain (Amygdala) Pool
0.0


Lung ca. NCI-H526
3.4
Brain (cerebellum)
0.0


Lung ca. NCI-H23
15.9
Brain (fetal)
0.7


Lung ca. NCI-H460
0.4
Brain (Hippocampus) Pool
0.0


Lung ca. HOP-62
4.5
Cerebral Cortex Pool
0.0


Lung ca. NCI-H522
25.5
Brain (Substantia
0.0




nigra) Pool


Liver
0.0
Brain (Thalamus) Pool
0.0


Fetal Liver
1.3
Brain (whole)
0.0


Liver ca. HepG2
6.6
Spinal Cord Pool
0.0


Kidney Pool
0.1
Adrenal Gland
0.1


Fetal Kidney
4.6
Pituitary gland Pool
0.0


Renal ca. 786-0
44.1
Salivary Gland
0.0


Renal ca. A498
4.2
Thyroid (female)
0.1


Renal ca. ACHN
15.2
Pancreatic ca.
48.3




CAPAN2


Renal ca. UO-31
20.4
Pancreas Pool
0.5










[1553]

823





TABLE AND










Panel 2.2













Rel. Exp. (%)
Rel. Exp. (%)

Rel. Exp. (%)
Rel. Exp. (%)



Ag3558, Run
Ag3558, Run

Ag3558, Run
Ag3558, Run


Tissue Name
173762113
174924057
Tissue Name
173762113
174924057















Normal Colon
12.5
5.6
Kidney Margin
3.3
1.1





(OD04348)


Colon cancer
100.0
100.0
Kidney
5.6
8.9


(OD06064)


malignant





cancer





(OD06204B)


Colon Margin
27.5
17.7
Kidney normal
0.6
0.3


(OD06064)


adjacent tissue





(OD06204E)


Colon cancer
3.1
4.8
Kidney Cancer
6.3
2.8


(OD06159)


(OD04450-01)


Colon Margin
5.6
7.3
Kidney Margin
0.6
0.0


(OD06159)


(OD04450-03)


Colon cancer
11.5
16.6
Kidney Cancer
0.0
0.0


(OD06297-04)


8120613


Colon Margin
12.5
7.8
Kidney Margin
0.3
0.3


(OD06297-05)


8120614


CC Gr.2 ascend
6.9
5.7
Kidney Cancer
0.2
1.9


colon


9010320


(ODO3921)


CC Margin
6.8
6.4
Kidney Margin
2.1
2.3


(ODO3921)


9010321


Colon cancer
6.8
4.9
Kidney Cancer
0.8
1.7


metastasis


8120607


(OD06104)


Lung Margin
17.9
12.6
Kidney Margin
0.3
0.0


(OD06104)


8120608


Colon mets to
15.1
23.3
Normal Uterus
1.6
0.5


lung


(OD04451-01)


Lung Margin
2.5
1.6
Uterine Cancer
3.5
3.6


(OD04451-02)


064011


Normal Prostate
2.1
0.0
Normal
0.3
0.0





Thyroid


Prostate Cancer
0.0
0.2
Thyroid Cancer
1.1
0.7


(OD04410)


064010


Prostate Margin
0.4
0.3
Thyroid Cancer
1.2
1.0


(OD04410)


A302152


Normal Ovary
2.7
0.4
Thyroid Margin
0.3
0.3





A302153


Ovarian cancer
30.1
32.8
Normal Breast
2.7
1.9


(OD06283-03)


Ovarian Margin
1.4
1.3
Breast Cancer
7.4
8.5


(OD06283-07)


(OD04566)


Ovarian Cancer
7.0
1.9
Breast Cancer
4.3
6.5


064008


1024


Ovarian cancer
1.2
1.9
Breast Cancer
11.8
13.9


(OD06145)


(OD04590-01)


Ovarian Margin
0.9
0.6
Breast Cancer
8.0
6.8


(OD06145)


Mets





(OD04590-03)


Ovarian cancer
28.1
30.4
Breast Cancer
7.9
11.0


(OD06455-03)


Metastasis





(OD04655-05)


Ovarian Margin
0.7
0.6
Breast Cancer
5.7
5.8


(OD06455-07)


064006


Normal Lung
1.4
1.3
Breast Cancer
0.7
0.3





9100266


Invasive poor
25.0
20.3
Breast Margin
1.8
1.1


diff. lung adeno


9100265


(ODO4945-01


Lung Margin
1.0
1.7
Breast Cancer
2.5
1.2


(ODO4945-03)


A209073


Lung Malignant
6.3
6.4
Breast Margin
3.0
1.2


Cancer


A2090734


(OD03126)


Lung Margin
1.3
1.0
Breast cancer
15.7
24.7


(OD03126)


(OD06083)


Lung Cancer
13.5
10.3
Breast cancer
16.5
15.0


(OD05014A)


node metastasis





(OD06083)


Lung Margin
3.1
4.8
Normal Liver
0.0
0.0


(OD05014B)


Lung cancer
38.4
28.7
Liver Cancer
1.2
0.0


(OD06081)


1026


Lung Margin
1.2
1.1
Liver Cancer
4.1
1.3


(OD06081)


1025


Lung Cancer
7.4
3.8
Liver Cancer
0.9
0.9


(OD04237-01)


6004-T


Lung Margin
0.8
1.9
Liver Tissue
2.2
1.4


(OD04237-02)


6004-N


Ocular
0.2
0.6
Liver Cancer
0.8
1.0


Melanoma


6005-T


Metastasis


Ocular
0.0
0.0
Liver Tissue
1.3
0.3


Melanoma


6005-N


Margin (Liver)


Melanoma
13.2
12.5
Liver Cancer
1.6
2.0


Metastasis


064003


Melanoma
1.6
1.1
Normal
4.4
4.4


Margin (Lung)


Bladder


Normal Kidney
0.3
0.0
Bladder Cancer
4.6
1.9





1023


Kidney Ca,
0.0
1.0
Bladder Cancer
23.0
15.4


Nuclear grade 2


A302173


(OD04338)


Kidney Margin
0.8
0.3
Normal
6.5
9.5


(OD04338)


Stomach


Kidney Ca
0.6
2.6
Gastric Cancer
2.9
3.2


Nuclear grade


9060397


1/2 (OD04339)


Kidney Margin
0.8
0.6
Stomach
4.9
1.0


(OD04339)


Margin





9060396


Kidney Ca,
0.6
1.2
Gastric Cancer
6.3
4.6


Clear cell type


9060395


(OD04340)


Kidney Margin
0.7
1.4
Stomach
3.5
3.0


(OD04340)


Margin





9060394


Kidney Ca,
36.9
31.0
Gastric Cancer
22.1
20.0


Nuclear grade 3


064005


(OD04348)










[1554]

824





TABLE ANE










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3558, Run

Ag3558, Run


Tissue Name
166488678
Tissue Name
166488678













Secondary Th1 act
17.9
HUVEC IL-1beta
10.3


Secondary Th2 act
12.4
HUVEC IFN gamma
12.2


Secondary Tr1 act
12.3
HUVEC TNF alpha +
12.8




IFN gamma


Secondary Th1 rest
1.7
HUVEC TNF alpha +
14.9




IL4


Secondary Th2 rest
2.6
HUVEC IL-11
8.6


Secondary Tr1 rest
2.5
Lung Microvascular EC
5.2




none


Primary Th1 act
9.1
Lung Microvascular EC
4.8




TNF alpha + IL-1beta


Primary Th2 act
11.6
Microvascular Dermal
19.5




EC none


Primary Tr1 act
11.4
Microsvasular Dermal
8.5




EC TNF alpha + IL-1beta


Primary Th1 rest
32.8
Bronchial epithelium
1.0




TNF alpha + IL1beta


Primary Th2 rest
10.4
Small airway epithelium
0.5




none


Primary Tr1 rest
13.4
Small airway epithelium
5.8




TNF alpha + IL-1beta


CD45RA CD4
10.7
Coronery artery SMC rest
2.3


lymphocyte act


CD45RO CD4
17.2
Coronery artery SMC
1.3


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
12.2
Astrocytes rest
1.4


Secondary CD8
11.7
Astrocytes TNF alpha +
0.7


lymphocyte rest

IL-1beta


Secondary CD8
10.4
KU-812 (Basophil) rest
3.1


lymphocyte act


CD4 lymphocyte none
0.1
KU-812 (Basophil)
6.6




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
6.0
CCD1106
11.3


CD95 CH11

(Keratinocytes) none


LAK cells rest
1.8
CCD1106
2.6




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
16.3
Liver cirrhosis
0.3


LAK cells IL-2 + IL-12
9.7
Lupus Kidney
0.0


LAK cells IL-2 + IFN
19.9
NCI-H292 none
12.2


gamma


LAK cells IL-2 + IL-18
16.4
NCI-H292 IL-4
29.7


LAK cells
0.7
NCI-H292 IL-9
24.3


PMA/ionomycin


NK Cells IL-2 rest
9.9
NCI-H292 IL-13
16.4


Two Way MLR 3 day
1.5
NCI-H292 IFN gamma
16.0


Two Way MLR 5 day
7.4
HPAEC none
8.9


Two Way MLR 7 day
6.1
HPAEC TNF alpha + IL-
5.5




1beta


PBMC rest
0.1
Lung fibroblast none
2.2


PBMC PWM
44.4
Lung fibroblast TNF
2.3




alpha + IL-1beta


PBMC PHA-L
23.3
Lung fibroblast IL-4
0.8


Ramos (B cell) none
13.4
Lung fibroblast IL-9
2.3


Ramos (B cell)
47.0
Lung fibroblast IL-13
0.5


ionomycin


B lymphocytes PWM
79.0
Lung fibroblast IFN
0.5




gamma


B lymphocytes CD40L
16.2
Dermal fibroblast
48.6


and IL-4

CCD1070 rest


EOL-1 dbcAMP
6.3
Dermal fibroblast
100.0




CCD1070 TNF alpha


EOL-1 dbcAMP
4.5
Dermal fibroblast
25.5


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
1.1
Dermal fibroblast IFN
14.0




gamma


Dendritic cells LPS
0.1
Dermal fibroblast IL-4
14.9


Dendritic cells anti-
0.1
IBD Colitis 2
0.5


CD40


Monocytes rest
0.0
IBD Crohn's
0.2


Monocytes LPS
0.0
Colon
1.7


Macropages rest
3.0
Lung
1.2


Macrophages LPS
0.4
Thymus
0.0


HUVEC none
18.7
Kidney
11.4


HUVEC starved
0.0










[1555] CNS_neurodegeneration_v1.0 Summary: Ag3558 Expression of the CG59371-0l gene is low/undetectable in all samples on this panel (CTs>35). (Data not shown.)


[1556] General_screening_panel_v1.4 Summary: Ag3558 Highest expression of the CG59371-01 gene is seen in a breast cancer cell line (CT=23.4). Overall, expression of this gene is significantly higher in cancer cell lines and fetal derived tissues than in samples derived from normal adult tissues. There are significant levels of expression in clusters of cell lines derived from pancreatic, brain, colon, gastric, renal, lung, ovarian, breast and melanoma cancers. Thus, expression of this gene in could be used to differentiate between the cancer derived samples and fetal tissues from other samples on this panel and as a marker to detect the presence of cancer. Furthermore, the much higher levels of expression in proliferative tissue suggest that this gene may be involved in cell proliferation. Therefore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of these cancers.


[1557] Among tissues with metabolic function, this gene is expressed at moderate to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.


[1558] This molecule is a novel protein phosphatase expressed at moderate to low levels in all regions of the CNS examined. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.


[1559] General_screening_panel_v1.5 Summary: Ag3558 Results from this experiment are in excellent agreement with results from Panel 1.4. Please see that panel for discussion of utility of this gene in cancer, metabolic disorders and the central nervous system.


[1560] Panel 2.2 Summary: Ag3558 Two experiments with the same probe and primer produce results that are in excellent agreement, with highest expression of the CG59371-01 gene in colon cancer (CTs=30). Furthermore, expression is higher in kidney, lung, ovary and colon cancers when compared to normal adjacent tissue. In addition, significant expression is also seen in gastric, breast, and bladder cancer. Thus, expression of this gene in could be used to differentiate between the cancer derived samples and other samples on this panel and as a marker to detect the presence of cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of these cancers.


[1561] Panel 4D Summary: Ag3558 The CG59371-01 gene is widely expressed among the samples on this panel, with highest expression in dermal fibroblasts treated with TNF-alpha. Significant levels of expression are also seen in treated and untreated samples from skin, lung, T-cells and B-cells. Therefore, modulation of the expression or activity of the protein encoded by this transcript through the application of antibodies or peptides therapeutics may be beneficial for the treatment of lung inflammatory diseases such as asthma, and chronic obstructive pulmonary diseases, inflammatory skin diseases such as psoriasis, atopic dermatitis, ulcerative dermatitis, and ulcerative colitis, autoimmune diseases such as Crohn's disease, lupus erythematosus, rheumatoid arthritis and osteoarthritis and in other diseases in which T cells and B cells are activated.


[1562] AO. CG59346-01: Cortactin-Binding Protein 1


[1563] Expression of gene CG59346-01 was assessed using the primer-probe set Ag3550, described in Table AOA. Results of the RTQ-PCR runs are shown in Tables AOB, AOC and AOD.


[1564] Table AOA. Probe Name Ag3550
825TABLE AOAProbe Name Ag3550SEQ IDPrimersSequenceLengthStart PositionNO:Forward5′-gccaacagagatgaacaaagag-3′223459520ProbeTET-5′-accgcctctccttctcccgctct-3′-TAMRA233508521Reverse5′-ttggaaggctaaagacatctga-3′223532522


[1565]

826





TABLE AOB










CNS_neurodegeneration_v1.0













Rel. Exp.





(%)



Rel. Exp. (%)

Ag3550,



Ag3550, Run

Run


Tissue Name
210641081
Tissue Name
210641081













AD 1 Hippo
12.8
Control (Path) 3
5.1




Temporal Ctx


AD 2 Hippo
38.7
Control (Path) 4
40.3




Temporal Ctx


AD 3 Hippo
10.4
AD 1 Occipital Ctx
18.8


AD 4 Hippo
15.8
AD 2 Occipital Ctx
0.0




(Missing)


AD 5 Hippo
79.6
AD 3 Occipital Ctx
7.2


AD 6 Hippo
49.3
AD 4 Occipital Ctx
25.9


Control 2 Hippo
37.4
AD 5 Occipital Ctx
37.6


Control 4 Hippo
10.3
AD 6 Occipital Ctx
19.6


Control (Path) 3
9.6
Control 1 Occipital
2.1


Hippo

Ctx


AD 1 Temporal
15.7
Control 2 Occipital
56.6


Ctx

Ctx


AD 2 Temporal
37.1
Control 3 Occipital
26.8


Ctx

Ctx


AD 3 Temporal
8.6
Control 4 Occipital
5.0


Ctx

Ctx


AD 4 Temporal
30.6
Control (Path) 1
93.3


Ctx

Occipital Ctx


AD 5 Inf Temporal
66.9
Control (Path) 2
14.6


Ctx

Occipital Ctx


AD 5 Sup
38.7
Control (Path) 3
2.6


Temporal Ctx

Occipital Ctx


AD 6 Inf Temporal
45.4
Control (Path) 4
23.8


Ctx

Occipital Ctx


AD 6 Sup
53.2
Control 1 Parietal
8.7


Temporal Ctx

Ctx


Control 1
7.3
Control 2 Parietal
48.0


Temporal Ctx

Ctx


Control 2
36.6
Control 3 Parietal
17.2


Temporal Ctx

Ctx


Control 3
29.7
Control (Path) 1
84.1


Temporal Ctx

Parietal Ctx


Control 3
14.6
Control (Path) 2
28.5


Temporal Ctx

Parietal Ctx


Control (Path) 1
100.0
Control (Path) 3
4.6


Temporal Ctx

Parietal Ctx


Control (Path) 2
65.5
Control (Path) 4
56.6


Temporal Ctx

Parietal Ctx










[1566]

827





TABLE AOC










General_screening_panel_v1.4











Rel. Exp. (%)

Rel. Exp. (%)



Ag3550, Run

Ag3550, Run


Tissue Name
217048931
Tissue Name
217048931













Adipose
0.5
Renal ca. TK-10
27.7


Melanoma* Hs688(A).T
1.4
Bladder
13.7


Melanoma*
1.6
Gastric ca. (liver met.)
25.0


Hs688(B).T

NCI-N87


Melanoma* M14
0.0
Gastric ca. KATO III
24.5


Melanoma*
0.0
Colon ca. SW-948
1.4


LOXIMVI


Melanoma* SK-MEL-5
0.8
Colon ca. SW480
8.8


Squamous cell
2.1
Colon ca.* (SW480
7.4


carcinoma SCC-4

met) SW620


Testis Pool
2.0
Colon ca. HT29
2.0


Prostate ca.* (bone
15.2
Colon ca. HCT-116
7.1


met) PC-3


Prostate Pool
6.7
Colon ca. CaCo-2
92.0


Placenta
18.9
Colon cancer tissue
6.0


Uterus Pool
0.0
Colon ca. SW1116
1.8


Ovarian ca.
7.6
Colon ca. Colo-205
3.0


OVCAR-3


Ovarian ca. SK-
14.9
Colon ca. SW-48
3.1


OV-3


Ovarian ca.
3.4
Colon Pool
2.2


OVCAR-4


Ovarian ca.
24.5
Small Intestine Pool
5.0


OVCAR-5


Ovarian ca.
2.1
Stomach Pool
6.9


IGROV-1


Ovarian ca.
2.4
Bone Marrow Pool
0.2


OVCAR-8


Ovary
1.4
Fetal Heart
0.1


Breast ca. MCF-7
34.6
Heart Pool
0.1


Breast ca. MDA-
8.2
Lymph Node Pool
2.8


MB-231


Breast ca. BT 549
0.2
Fetal Skeletal Muscle
0.2


Breast ca. T47D
57.4
Skeletal Muscle Pool
0.0


Breast ca. MDA-N
0.0
Spleen Pool
1.8


Breast Pool
4.6
Thymus Pool
7.2


Trachea
14.1
CNS cancer
0.1




(glio/astro) U87-MG


Lung
0.0
CNS cancer
0.1




(glio/astro) U118-MG


Fetal Lung
19.5
CNS cancer
0.0




(neuro; met) SK-N-AS


Lung ca. NCI-N417
1.5
CNS cancer (astro) SF-
0.0




539


Lung ca. LX-1
24.7
CNS cancer (astro)
0.0




SNB-75


Lung ca. NCI-H146
7.4
CNS cancer (glio)
2.1




SNB-19


Lung ca. SHP-77
0.2
CNS cancer (glio) SF-
0.1




295


Lung ca. A549
26.1
Brain (Amygdala) Pool
22.1


Lung ca. NCI-H526
13.9
Brain (cerebellum)
63.3


Lung ca. NCI-H23
6.6
Brain (fetal)
100.0


Lung ca. NCI-H460
11.1
Brain (Hippocampus) Pool
28.1


Lung ca. HOP-62
0.2
Cerebral Cortex Pool
34.2


Lung ca. NCI-H522
0.5
Brain (Substantia
26.2




nigra) Pool


Liver
3.6
Brain (Thalamus) Pool
37.9


Fetal Liver
19.1
Brain (whole)
57.8


Liver ca. HepG2
26.4
Spinal Cord Pool
2.8


Kidney Pool
0.3
Adrenal Gland
2.6


Fetal Kidney
11.7
Pituitary gland Pool
3.6


Renal ca. 786-0
23.3
Salivary Gland
25.5


Renal ca. A498
11.0
Thyroid (female)
6.9


Renal ca. ACHN
27.7
Pancreatic ca.
15.3




CAPAN2


Renal ca. UO-31
12.7
Pancreas Pool
12.9










[1567]

828





TABLE AOD










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3550, Run

Ag3550, Run


Tissue Name
166453850
Tissue Name
166453850













Secondary Th1 act
0.2
HUVEC IL-1beta
0.0


Secondary Th2 act
0.1
HUVEC IFN gamma
0.0


Secondary Tr1 act
0.0
HUVEC TNF alpha +
0.0




IFN gamma


Secondary Th1 rest
0.0
HUVEC TNF alpha +
0.0




IL4


Secondary Th2 rest
0.0
HUVEC IL-11
0.0


Secondary Tr1 rest
0.0
Lung Microvascular EC
0.0




none


Primary Th1 act
0.0
Lung Microvascular EC
0.0




TNF alpha + IL-1beta


Primary Th2 act
0.0
Microvascular Dermal
0.0




EC none


Primary Tr1 act
0.0
Microsvasular Dermal
0.0




EC TNF alpha + IL-1beta


Primary Th1 rest
0.0
Bronchial epithelium
9.5




TNF alpha + IL1beta


Primary Th2 rest
0.0
Small airway epithelium
8.1




none


Primary Tr1 rest
0.0
Small airway epithelium
27.2




TNF alpha + IL-1beta


CD45RA CD4
1.4
Coronery artery SMC rest
0.7


lymphocyte act


CD45RO CD4
0.0
Coronery artery SMC
1.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
0.0
Astrocytes rest
5.2


Secondary CD8
0.0
Astrocytes TNF alpha +
5.9


lymphocyte rest

IL-1beta


Secondary CD8
0.0
KU-812 (Basophil) rest
0.0


lymphocyte act


CD4 lymphocyte none
0.0
KU-812 (Basophil)
0.1




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
0.0
CCD1106
10.5


CD95 CH11

(Keratinocytes) none


LAK cells rest
0.0
CCD1106
23.0




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
0.0
Liver cirrhosis
22.8


LAK cells IL-2 + IL-12
0.1
Lupus kidney
22.5


LAK cells IL-2 + IFN
0.0
NCI-H292 none
66.0


gamma


LAK cells IL-2 + IL-18
0.0
NCI-H292 IL-4
81.8


LAK cells
0.0
NCI-H292 IL-9
69.7


PMA/ionomycin


NK Cells IL-2 rest
0.0
NCI-H292 IL-13
58.6


Two Way MLR 3 day
0.0
NCI-H292 IFN gamma
61.1


Two Way MLR 5 day
0.0
HPAEC none
0.0


Two Way MLR 7 day
0.0
HPAEC TNF alpha + IL-
0.0




1beta


PBMC rest
0.0
Lung fibroblast none
57.4


PBMC PWM
0.0
Lung fibroblast TNF
45.7




alpha + IL-1beta


PBMC PHA-L
0.0
Lung fibroblast IL-4
36.6


Ramos (B cell) none
0.0
Lung fibroblast IL-9
33.9


Ramos (B cell)
0.0
Lung fibroblast IL-13
17.2


ionomycin


B lymphocytes PWM
2.4
Lung fibroblast IFN
34.9




gamma


B lymphocytes CD40L
11.3
Dermal fibroblast
28.5


and IL-4

CCD1070 rest


EOL-1 dbcAMP
0.0
Dermal fibroblast
11.3




CCD1070 TNF alpha


EOL-1 dbcAMP
0.0
Dermal fibroblast
4.8


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
0.0
Dermal fibroblast IFN
0.3




gamma


Dendritic cells LPS
0.0
Dermal fibroblast IL-4
0.0


Dendritic cells anti-
0.3
IBD Colitis 2
6.9


CD40


Monocytes rest
36.3
IBD Crohn's
2.0


Monocytes LPS
0.0
Colon
36.6


Macrophages rest
0.0
Lung
14.3


Macrophages LPS
0.0
Thymus
100.0


HUVEC none
0.0
Kidney
0.1


HUVEC starved
0.0










[1568] CNS_neurodegeneration_v1.0 Summary: Ag3550 This panel does not show differential expression of the CG59346-01 gene in Alzheimer's disease. However, this expression profile confirms the presence of this gene in the brain. Please see Panel 1.4 for discussion of utility of this gene in the central nervous system.


[1569] General_screening_panel_v1.4 Summary: Ag3550 Highest expression of the CG59346-01 gene is seen in the brain. Expression of this gene is seen at high levels in the cerebellum, cerebral cortex, and thalamus and at moderate levels in the amygdala, hippocampus, and thalamus. This CG59346-01 gene encodes a homologue of Proline-rich synapse-associated protein-1/cortactin binding protein 1 (ProSAP1/CortBP1). ProSAP1 is PDZ-domain protein highly enriched in the postsynaptic density (PSD) and involved in in the assembly of the PSD during neuronal differentiation that may function with contactin, in the recruitment and activation of neural intracellular signaling pathways. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[1570] In addition, moderate levels of expression are seen in colon, gastric, renal, pancreatic, lung, ovarian, breast and prostate cancer cell lines. Thus, expression of this gene could be used to detect the presence of cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of these cancers.


[1571] Among tissues with metabolic function, this gene is expressed at moderate to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.


[1572] In addition, this gene is expressed at higher levels in fetal lung and kidney (CTs=29) when compared to expression in adult lung and kidney (CTs=35-40). Thus, expression of this gene could be used to differentiate between the two sources of lung and kidney tissue.



REFERENCES

[1573] 1. Peles E, Nativ M, Lustig M, Grumet M, Schilling J, Martinez R, Plowman G D, Schlessinger J. Identification of a novel contactin-associated transmembrane receptor with multiple domains implicated in protein-protein interactions. EMBO J. Mar. 3, 1997;16(5):978-88.


[1574] 2. Boeckers T M, Kreutz M R, Winter C, Zuschratter W, Smalla K H, Sanmarti-Vila L, Wex H, Langnaese K, Bockmann J, Garner C C, Gundelfinger E D. (1999) Proline-rich synapse-associated protein-1/cortactin binding protein 1 (ProSAP1/CortBP1) is a PDZ-domain protein highly enriched in the postsynaptic density. J Neurosci Aug. 1, 1999;19(15):6506-18.


[1575] Panel 4D Summary: Ag3550 Highest expression of the CG59346-01 gene is seen in thymus (CT=27). In addition, significant levels of expression are seen in IL-4, IL-9, IL-13 and IFN gamma activated-NCI-H292 mucoepidermoid cells as well as untreated NCI-H292 cells. Moderate/low expression is also detected in IL-4, IL-9, IL-13 and IFN gamma activated lung fibroblasts, small airway epithelium (treated and untreated), and treated bronchial epithelium. The expression of this gene in cells derived from or within the lung suggests, that this gene may be involved in normal conditions as well as pathological and inflammatory lung disorders that include chronic obstructive pulmonary disease, asthma, allergy and emphysema.


[1576] In addition, significant levels of expression are seen in treated and untreated dermal fibroblasts and keratinocytes, suggesting that modulation of the expression or function of this gene may also reduce symtptoms in inflammatory skin diseases such as psoriasis, atopic dermatitis, and ulcerative dermatitis.


[1577] AP. CG57814-01 and CG57814-02: Basic I 19 Protein


[1578] Expression of gene CG57814-01 and varian CG57814-02 was assessed using the primer-p robe set Ag791, described in Table APA.


[1579] Table APA. Probe Name Ag791
829TABLE APAProbe Name Ag791StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-aaatgtgatgaccaaggttctg-3′221290523ProbeTET-5′-agcacacattatccagcgaaagcatg-3′-TAMRA261319524Reverse5′-tgtcaaagaaacccttgttgtc-3′221368525


[1580] Panel 1.2 Summary: Ag791 Expression of the CG57814-01 gene is low/undetectable in all samples on this panel (CTs>35). (Data not shown.)


[1581] AQ. CG59327-01: Monocarboxylate Transporter 1 Like Protein


[1582] Expression of gene CG59327-01 was assessed using the primer-probe set Ag3548, described in Table AQA. Results of the RTQ-PCR runs are shown in Tables AQB and AQC.


[1583] Table AOA. Probe Name Ag3548
830TABLE AQAProbe Name Ag3548StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-atttgcatacagcagctttgtc-3′22517526ProbeTET-5′-ttcatctcccagaaatcgtcaatttg-3′-TAMRA26549527Reverse5′-accttcgtttgctccaataagt-3′22579528


[1584]

831















Rel. Exp. (%)

Rel. Exp. (%)



Ag3548, Run

Ag3548, Run


Tissue Name
217048438
Tissue Name
217048428


















Adipose
0.0
Renal ca. TK-10
3.6


Melanoma* Hs688(A).T
0.0
Bladder
0.0


Melanoma*
0.0
Gastric ca. (liver met.)
0.0


Hs688(B).T

NCI-N87


Melanoma* M14
0.0
Gastric ca. KATO III
0.0


Melanoma*
0.0
Colon ca. SW-948
0.0


LOXIMVI


Melanoma* SK-MEL-5
0.0
Colon ca. SW480
1.3


Squamous cell
0.0
Colon ca.* (SW480
0.0


carcinoma SCC-4

met) SW620


Testis Pool
0.0
Colon ca. HT29
0.0


Prostate ca.* (bone
0.0
Colon ca. HCT-116
0.0


met) PC-3


Prostate Pool
0.0
Colon ca. CaCo-2
0.0


Placenta
0.0
Colon cancer tissue
0.0


Uterus Pool
1.2
Colon ca. SW1116
0.0


Ovarian ca.
0.0
Colon ca. Colo-205
0.0


OVCAR-3


Ovarian ca. SK-OV-3
0.0
Colon ca. SW-48
0.0


Ovarian ca.
0.0
Colon Pool
2.2


OVCAR-4


Ovarian ca.
0.0
Small Intestine Pool
0.0


OVCAR-5


Ovarian ca.
0.0
Stomach Pool
0.0


IGROV-1


Ovarian ca.
0.0
Bone Marrow Pool
0.0


OVCAR-8


Ovary
0.0
Fetal Heart
0.0


Breast ca. MCF-7
0.0
Heart Pool
0.0


Breast ca. MDA-
0.0
Lymph Node Pool
0.0


MB-231


Breast ca. BT 549
1.9
Fetal Skeletal Muscle
0.0


Breast ca. T47D
0.0
Skeletal Muscle Pool
0.0


Breast ca. MDA-N
0.0
Spleen Pool
0.0


Breast Pool
0.0
Thymus Pool
0.0


Trachea
0.0
CNS cancer
0.0




(glio/astro) U87-MG


Lung
2.4
CNS cancer
6.5




(glio/astro) U-118-MG


Fetal Lung
0.0
CNS cancer
0.0




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.0
CNS cancer (astro) SF-
0.0




539


Lung ca. LX-1
0.0
CNS cancer (astro)
6.4




SNB-75


Lung ca. NCI-H146
0.0
CNS cancer (glio)
0.0




SNB-19


Lung ca. SHP-77
0.0
CNS cancer (glio) SF-
0.0




295


Lung ca. A549
0.0
Brain (Amygdala) Pool
0.0


Lung ca. NCI-H526
0.0
Brain (cerebellum)
0.0


Lung ca. NCI-H23
0.0
Brain (fetal)
0.0


Lung ca. NCI-H460
0.0
Brain (Hippocampus) Pool
0.0


Lung ca. HOP-62
0.0
Cerebral Cortex Pool
0.0


Lung ca. NCI-H522
3.1
Brain (Substantia
0.0




nigra) Pool


Liver
0.0
Brain (Thalamus) Pool
0.0


Fetal Liver
0.0
Brain (whole)
0.0


Liver ca. HepG2
0.0
Spinal Cord Pool
0.0


Kidney Pool
0.0
Adrenal Gland
0.0


Fetal Kidney
3.4
Pituitary gland Pool
0.0


Renal ca. 786-0
0.0
Salivary Gland
0.0


Renal ca. A498
100.0
Thyroid (female)
0.0


Renal ca. ACHN
0.0
Pancreatic ca.
0.0




CAPAN2


Renal ca. UO-31
0.0
Pancreas Pool
0.0










[1585]

832





TABLE AQC










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3548, Run

Ag3548, Run


Tissue Name
166453848
Tissue Name
166453848













SecondaryTh1 act
0.0
HUVEC IL-1beta
0.0


Secondary Th2 act
0.0
HUVEC IFN gamma
0.0


Secondary Tr1 act
0.0
HUVEC TNF alpha +
0.0




IFN gamma


Secondary Th1 rest
0.0
HUVEC TNF alpha +
0.0




IL4


Secondary Th2 rest
0.0
HUVEC IL-11
0.5


Secondary Tr1 rest
0.0
Lung Microvascular EC
0.0




none


PrimaryTh1 act
0.0
Lung Microvascular EC
0.0




TNF alpha + IL-1beta


Primary Th2 act
0.0
Microvascular Dermal
100.0




EC none


Primary Tr1 act
0.0
Microsvasular Dermal
0.0




EC TNF alpha + IL-1beta


Primary Th1 rest
0.0
Bronchial epithelium
0.2




TNF alpha + IL-1beta


Primary Th2 rest
0.0
Small airway epithelium
1.2




none


Primary Tr1 rest
0.0
Small airway epithelium
0.0




TNF alpha + IL-1beta


CD45RA CD4
0.0
Coronery artery SMC rest
0.0


lymphocyte act


CD45RO CD4
0.0
Coronery artery SMC
0.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
0.0
Astrocytes rest
0.3


Secondary CD8
0.0
Astrocytes TNF alpha +
0.0


lymphocyte rest

IL-1beta


Secondary CD8
0.0
KU-812 (Basophil) rest
0.0


lymphocyte act


CD4 lymphocyte none
0.0
KU-812 (Basophil)
0.3




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
0.0
CCD1106
0.0


CD95 CH11

(Keratinocytes) none


LAK cells rest
0.0
CCD1106
0.0




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
0.0
Liver cirrhosis
6.5


LAK cells IL-2 + IL-12
0.0
Lupus kidney
0.7


LAK cells IL-2 + IFN
0.0
NCI-H292 none
1.8


gamma


LAK cells IL-2 + IL-18
0.0
NCI-H292 IL-4
1.7


LAK cells
0.0
NCI-H292 IL-9
0.2


PMA/ionomycin


NK Cells IL-2 rest
0.0
NCI-H292 IL-13
0.0


Two Way MLR 3 day
0.0
NCI-H292 IFN gamma
0.0


Two Way MLR 5 day
0.0
HPAEC none
0.5


Two Way MLR 7 day
0.0
HPAEC TNF alpha + IL-
0.0




1beta


PBMC rest
0.0
Lung fibroblast none
0.0


PBMC PWM
0.0
Lung fibroblast TNF
0.0




alpha + IL-1beta


PBMC PHA-L
0.0
Lung fibroblast IL-4
0.0


Ramos (B cell) none
0.0
Lung fibroblast IL-9
0.0


Ramos (B cell)
0.0
Lung fibroblast IL-13
0.0


ionomycin


B lymphocytes PWM
0.0
Lung fibroblast IFN
0.0




gamma


B lymphocytes CD40L
0.0
Dermal fibroblast
0.0


and IL-4

CCD1070 rest


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0




CCD1070 TNF alpha


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
0.0
Dermal fibroblast IFN
0.0




gamma


Dendritic cells LPS
0.0
Dermal fibroblast IL-4
0.0


Dendritic cells anti-
0.0
IBD Colitis 2
2.0


CD40


Monocytes rest
0.0
IBD Crohn's
3.5


Monocytes LPS
0.0
Colon
1.0


Macrophages rest
0.0
Lung
2.3


Macrophages LPS
0.0
Thymus
0.7


HUVEC none
0.0
Kidney
0.0


HUVEC starved
0.4










[1586] CNS_neurodegeneration_v1.0 Summary: Ag3548 Expression of the CG59327-01 gene is low/undetectable in all the samples on the panel (CTs>35). (Data not shown.)


[1587] General_screening_panel_v1.4 Summary: Ag3548 Significant expression of the CG59327-01 gene is restricted to a sample derived from a kidney cancer cell line (CT=33.34). Thus, expression of this gene could be used to differentiate between this sample and other samples on this panel and as a marker to detect the presence of kidney cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of kidney cancer.


[1588] Panel 4D Summary: Ag3548 Significant expression of the CG59327-01 gene is restricted to a samples derived from untreated microvascular dermal endothelial cells (CT=30.3). Thus, expression of this gene could be used as a marker of these cells.


[1589] AR. CG59494-01: Myelin P2


[1590] Expression of gene CG59494-01, which represents a full length physical clone, was assessed using the primer-probe set Ag3206, described in Table ARA. Results of the RTQ-PCR runs are shown in Tables ARB and ARC.


[1591] Table ARA. Probe Name Ag3206
833TABLE ARAProbe Name Ag3206StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-agtgttgatgggaaaatgatga-3′22160455ProbeTET-5′-ccataagaacagaaagttctttccaggaca-3′-TAMRA30182758Reverse5′-ccccagcttgaaggagatc-3′19216759


[1592]

834





TABLE ARB










Panel 1.3D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3206, Run

Ag3206, Run


Tissue Name
165527079
Tissue Name
165527079













Liver adenocarcinoma
0.0
Kidney (fetal)
10.5


Pancreas
0.0
Renal ca. 786-0
0.0


Pancreatic ca. CAPAN 2
17.8
Renal ca. A498
15.6


Adrenal gland
0.0
Renal ca. RXF 393
0.0


Thyroid
0.0
Renal ca. ACHN
14.8


Salivary gland
0.0
Renal ca. UO-31
0.0


Pituitary gland
0.0
Renal ca. TK-10
0.0


Brain (fetal)
0.0
Liver
0.0


Brain (whole)
9.9
Liver (fetal)
0.0


Brain (amygdala)
0.0
Liver ca.
0.0




(hepatoblast) HepG2


Brain (cerebellum)
0.0
Lung
0.0


Brain (hippocampus)
0.0
Lung (fetal)
0.0


Brain (substantia nigra)
0.0
Lung ca. (small cell) LX-1
4.5


Brain (thalamus)
0.0
Lung ca. (small cell)
0.0




NCI-H69


Cerebral Cortex
0.0
Lung ca. (s.cell var.)
18.0




SHP-77


Spinal cord
33.4
Lung ca. (large
41.2




cell)NCI-H460


glio/astro U87-MG
0.0
Lung ca. (non-sm.
0.0




cell) A549


glio/astro U-118-MG
0.0
Lung ca. (non-s.cell)
0.0




NCI-H23


astrocytoma SW1783
0.0
Lung ca. (non-s.cell)
0.0




HOP-62


neuro*; met SK-N-AS
0.0
Lung ca. (non-s.cl)
0.0




NCI-H522


astrocytoma SF-539
0.0
Lung ca. (squam.)
0.0




SW 900


astrocytoma SNB-75
11.7
Lung ca. (squam.)
0.0




NCI-H596


glioma SNB-19
0.0
Mammary gland
14.4


glioma U251
0.0
Breast ca.* (pl.ef)
0.0




MCF-7


glioma SF-295
0.0
Breast ca.* (pl.ef)
0.0




MDA-MB-231


Heart (fetal)
0.0
Breast ca.* (pl.ef)
0.0




T47D


Heart
15.5
Breast ca. BT-549
0.0


Skeletal muscle (fetal)
0.0
Breast ca. MDA-N
0.0


Skeletal muscle
0.0
Ovary
0.0


Bone marrow
0.0
Ovarian ca.
14.0




OVCAR-3


Thymus
0.0
Ovarian ca.
0.0




OVCAR-4


Spleen
0.0
Ovarian ca.
0.0




OVCAR-5


Lymph node
0.0
Ovarian ca.
0.0




OVCAR-8


Colorectal
0.0
Ovarian ca. IGROV-1
11.6


Stomach
0.0
Ovarian ca.*
0.0




(ascites) SK-OV-3


Small intestine
0.0
Uterus
0.0


Colon ca. SW480
0.0
Placenta
0.0


Colon ca.*
0.0
Prostate
0.0


SW620(SW480 met)


Colon ca. HT29
0.0
Prostate ca.* (bone
100.0




met)PC-3


Colon ca. HCT-116
0.0
Testis
27.5


Colon ca. CaCo-2
42.0
Melanoma
0.0




Hs688(A).T


Colon ca.
0.0
Melanoma* (met)
0.0


tissue(ODO3866)

Hs688(B).T


Colon ca. HCC-2998
0.0
Melanoma UACC-62
0.0


Gastric ca.* (liver met)
0.0
Melanoma M14
0.0


NCI-N87


Bladder
0.0
Melanoma LOX
0.0




IMVI


Trachea
0.0
Melanoma* (met)
0.0




SK-MEL-5


Kidney
0.0
Adipose
0.0










[1593]

835





TABLE ARC










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3206, Run

Ag3206, Run


Tissue Name
164531735
Tissue Name
164531735













Secondary Th1 act
0.0
HUVEC IL-1beta
0.0


Secondary Th2 act
11.9
HUVEC IFN gamma
0.0


Secondary Tr1 act
0.0
HUVEC TNF alpha +
12.6




IFN gamma


Secondary Th1 rest
11.9
HUVEC TNF alpha +
15.9




IL4


Secondary Th2 rest
0.0
HUVEC IL-11
0.0


Secondary Tr1 rest
0.0
Lung Microvascular EC
75.8




none


Primary Th1 act
0.0
Lung Microvascular EC
100.0




TNF alpha + IL-1beta


Primary Th2 act
0.0
Microvascular Dermal
72.2




EC none


Primary Tr1 act
0.0
Microsvasular Dermal
0.0




EC TNF alpha + IL-1beta


Primary Th1 rest
0.0
Bronchial epithelium
0.0




TNF alpha + IL1beta


Primary Th2 rest
0.0
Small airway epithelium
0.0




none


Primary Tr1 rest
0.0
Small airway epithelium
0.0




TNF alpha + IL-1beta


CD45RA CD4
0.0
Coronery artery SMC rest
0.0


lymphocyte act


CD45RO CD4
0.0
Coronery artery SMC
0.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
0.0
Astrocytes rest
0.0


Secondary CD8
0.0
Astrocytes TNF alpha +
0.0


lymphocyte rest

IL-1beta


Secondary CD8
0.0
KU-812 (Basophil) rest
0.0


lymphocyte act


CD4 lymphocyte none
0.0
KU-812 (Basophil)
0.0




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
0.0
CCD1106
0.0


CD95 CH11

(Keratinocytes) none


LAK cells rest
0.0
CCD1106
0.0




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
0.0
Liver cirrhosis
29.7


LAK cells IL-2 + IL-12
0.0
Lupus kidney
0.0


LAK cells IL-2 + IFN
0.0
NCI-H292 none
97.3


gamma


LAK cells IL-2 + IL-18
0.0
NCI-H292 IL-4
0.0


LAK cells
0.0
NCI-H292 IL-9
43.8


PMA/ionomycin


NK Cells IL-2 rest
7.8
NCI-H292 IL-13
24.0


Two Way MLR 3 day
0.0
NCI-H292 IFN gamma
12.7


Two Way MLR 5 day
0.0
HPAEC none
14.3


Two Way MLR 7 day
0.0
HPAEC TNF alpha + IL-
33.2




1beta


PBMC rest
0.0
Lung fibroblast none
0.0


PBMC PWM
0.0
Lung fibroblast TNF
0.0




alpha + IL-1beta


PBMC PHA-L
0.0
Lung fibroblast IL-4
0.0


Ramos (B cell) none
0.0
Lung fibroblast IL-9
16.2


Ramos (B cell)
0.0
Lung fibroblast IL-13
15.9


ionomycin


B lymphocytes PWM
0.0
Lung fibroblast IFN
0.0




gamma


B lymphocytes CD40L
0.0
Dermal fibroblast
0.0


and IL-4

CCD1070 rest


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0




CCD1070 TNF alpha


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
0.0
Dermal fibroblast IFN
0.0




gamma


Dendritic cells LPS
0.0
Dermal fibroblast IL-4
15.0


Dendritic cells anti-
0.0
IBD Colitis 2
27.4


CD40


Monocytes rest
0.0
IBD Crohn's
0.0


Monocytes LPS
0.0
Colon
6.7


Macrophages rest
0.0
Lung
0.0


Macrophages LPS
0.0
Thymus
0.0


HUVEC none
27.7
Kidney
0.0


HUVEC starved
20.0










[1594] Panel 1.3D Summary: Ag3206 Expression of the CG59494-01 gene is restricted to a sample derived from a prostate cancer cell line (CT=34.9). Thus, expression of this gene could be used to differentiate between this sample and other samples on this panel and as a marker to detect the presence of prostate cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of prostate cancer.


[1595] Panel 4D Summary: Ag3206 Expression of the CG59494-01 gene is primarily restricted to a cluster of samples derived from microvasculature of the lung and the dermis suggesting a role for this gene in the maintenance of the integrity of the microvasculature. Therefore, therapeutics designed for this putative protein could be beneficial for the treatment of diseases associated with damaged microvasculature including heart diseases or inflammatory diseases, such as psoriasis, asthma, and chronic obstructive pulmonary diseases.


[1596] AS. CG59432-01 and CG59432-02: Chloride Channel


[1597] Expression of gene CG59432-01 and CG59432-02 was assessed using the primer-110 probe set Ag5938, described in Table ASA. Results of the RTQ-PCR runs are shown in Tables ASB and ASC. Please note that CG59432-02 represents a full-length physical clone of CG59432-01 gene, validating the prediction of the gene sequence.


[1598] Table ASA. Probe Name Ag5938
836TABLE ASAProbe Name Ag5938SEQ IDPrimersSequencesLengthStart PositionNO:Forward5′-ttgtgtcagtctataccattaa-3′22626529ProbeTET-5′-accagcttggcctctgtccagt-3′-TAMRA22658530Reverse5′-tcctggagttcagagtatatct-3′22710531


[1599]

837





TABLE ASB










General_screening_panel_v1.5











Rel. Exp. (%)

Rel. Exp. (%)



Ag5938, Run

Ag5938, Run


Tissue Name
248102142
Tissue Name
248102142













Adipose
6.3
Renal ca. TK-10
2.7


Melanoma* Hs688(A).T
0.0
Bladder
17.6


Melanoma*
0.0
Gastric ca. (liver met.)
100.0


Hs688(B).T

NCI-N87


Melanoma* M14
0.0
Gastric ca. KATO III
8.2


Melanoma*
0.0
Colon ca. SW-948
0.0


LOXIMVI


Melanoma* SK-MEL-5
0.0
Colon ca. SW480
7.5


Squamous cell
21.5
Colon ca.* (SW480
0.6


carcinoma SCC-4

met) SW620


Testis Pool
21.0
Colon ca. HT29
7.1


Prostate ca.* (bone
0.0
Colon ca. HCT-116
11.0


met) PC-3


Prostate Pool
6.9
Colon ca. CaCo-2
25.2


Placenta
0.0
Colon cancer tissue
4.7


Uterus Pool
1.5
Colon ca. SW1116
2.7


Ovarian ca.
20.2
Colon ca. Colo-205
0.0


OVCAR-3


Ovarian ca. SK-OV-3
0.0
Colon ca. SW-48
0.0


Ovarian ca.
0.0
Colon Pool
5.7


OVCAR-4


Ovarian ca.
24.7
Small Intestine Pool
7.6


OVCAR-5


Ovarian ca.
0.0
Stomach Pool
3.2


IGROV-1


Ovarian ca.
2.8
Bone Marrow Pool
6.6


OVCAR-8


Ovary
0.0
Fetal Heart
1.0


Breast ca. MCF-7
4.2
Heart Pool
4.3


Breast ca. MDA-
0.0
Lymph Node Pool
3.8


MB-231


Breast ca. BT 549
0.0
Fetal Skeletal Muscle
59.9


Breast ca. T47D
0.0
Skeletal Muscle Pool
93.3


Breast ca. MDA-N
0.0
Spleen Pool
3.2


Breast Pool
10.4
Thymus Pool
3.6


Trachea
15.1
CNS cancer
0.0




(glio/astro) U87-MG


Lung
0.6
CNS cancer
3.1




(glio/astro) U-118-MG


Fetal Lung
31.6
CNS cancer
0.0




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.0
CNS cancer (astro) SF-
0.0




539


Lung ca. LX-1
0.0
CNS cancer (astro)
0.0




SNB-75


Lung ca. NCI-H146
3.2
CNS cancer (glio)
3.6




SNB-19


Lung ca. SHP-77
0.0
CNS cancer (glio) SF-
0.0




295


Lung ca. A549
0.0
Brain (Amygdala) Pool
47.3


Lung ca. NCI-H526
32.8
Brain (cerebellum)
15.3


Lung ca. NCI-H23
0.0
Brain (fetal)
1.8


Lung ca. NCI-H460
0.0
Brain (Hippocampus) Pool
15.8


Lung ca. HOP-62
0.0
Cerebral Cortex Pool
27.0


Lung ca. NCI-H522
0.0
Brain (Substantia
25.2




nigra) Pool


Liver
0.0
Brain (Thalamus) Pool
29.1


Fetal Liver
7.0
Brain (whole)
9.5


Liver ca. HepG2
0.0
Spinal Cord Pool
11.0


Kidney Pool
6.8
Adrenal Gland
8.4


Fetal Kidney
17.1
Pituitary gland Pool
6.3


Renal ca. 786-0
0.0
Salivary Gland
4.8


Renal ca. A498
0.0
Thyroid (female)
0.0


Renal ca. ACHN
0.0
Pancreatic ca.
1.4




CAPAN2


Renal ca. UO-31
0.0
Pancreas Pool
4.5










[1600]

838





TABLE ASC










Panel 5 Islet











Rel. Exp. (%)

Rel. Exp. (%)



Ag5938, Run

Ag5938, Run


Tissue Name
248045753
Tissue Name
248045753













97457_Patient-
0.0
94709_Donor 2 AM - A_adipose
0.0


02go_adipose


97476_Patient-
0.0
94710_Donor 2 AM - B_adipose
0.0


07sk_skeletal muscle


97477_Patient-
0.0
94711_Donor 2 AM - C_adipose
0.0


07ut_uterus


97478_Patient-
1.1
94712_Donor 2 AD - A_adipose
0.0


07pl_placenta


99167_Bayer Patient 1
0.0
94713_Donor 2 AD - B_adipose
0.0


97482_Patient-
0.0
94714_Donor 2 AD - C_adipose
0.0


08ut_uterus


97483_Patient-
0.0
94742_Donor 3 U -
0.0


08pl_placenta

A_Mesenchymal Stem Cells


97486_Patient-
0.0
94743_Donor 3 U -
0.0


09sk_skeletal muscle

B_Mesenchymal Stem Cells


97487_Patient-
0.0
94730_Donor 3 AM - A_adipose
0.7


09ut_uterus


97488_Patient-
0.5
94731_Donor 3 AM - B_adipose
0.0


09pl_placenta


97492_Patient-
0.0
94732_Donor 3 AM - C_adipose
0.0


10ut_uterus


97493_Patient-
0.4
94733_Donor 3 AD - A_adipose
0.0


10pl_placenta


97495_Patient-
1.0
94734_Donor 3 AD - B_adipose
0.0


11go_adipose


97496_Patient-
2.4
94735_Donor 3 AD - C_adipose
0.0


11sk_skeletal muscle


97497_Patient-
0.0
77138_Liver_HepG2untreated
0.0


11ut_uterus


97498_Patient-
0.0
73556_Heart_Cardiac stromal
0.0


11pl_placenta

cells (primary)


97500_Patient-
0.7
81735_Small Intestine
100.0


12go_adipose


97501_Patient-
6.8
72409_Kidney_Proximal
0.0


12sk_skeletal muscle

Convoluted Tubule


97502_Patient-
0.0
82685_Small
4.6


12ut_uterus

intestine_Duodenum


97503_Patient-
0.0
90650_Adrenal_Adrenocortical
0.0


12pl_placenta

adenoma


94721_Donor 2 U -
0.0
72410_Kidney_HRCE
0.0


A_Mesenchymal


Stem Cells


94722_Donor 2 U -
0.0
72411_Kidney_HRE
0.0


B_Mesenchymal


Stem Cells


94723_Donor 2 U -
6.5
73139_Uterus_Uterine smooth
0.0


C_Mesenchymal

muscle cells


Stem Cells










[1601] General_screening_panel_v1.5 Summary: Ag5938 Highest expression of the CG59432-01 gene is seen in a gastric cancer cell line (CT=32.5). Thus, expression of this gene could be used to differentiate between this sample and other samples on this panel. In addition, low expression of this gene is seen in colon cancer CaCo-2, lung cancer NCI-H526, ovarian cancer OVCAR-5, and squamous cell carcinoma SCC-4 cell lines. Therefore, therapeutic modulation of the activity of this gene or its protein product, through the use of small molecule drugs, protein therapeutics or antibodies, might be beneficial in the treatment of these cancers.


[1602] Significant expression is also detected in fetal skeletal muscle and adult skeletal muscle (CT=32.5). At least 50 disease-causing mutations in the skeletal muscle voltage-gated chloride channel gene (CLCN1), almost all of which originate from Caucasian families, have been identified. Therefore, therapeutic modulation of this gene product, a chloride channel homolog, may be a treatment for myotonia congenita and other muscle channelopathies.


[1603] In addition, this gene is expressed at low levels in most regions of the central nervous system examined, including amygdala, substantia nigra, thalamus, and cerebral cortex. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.



REFERENCES

[1604] 1. Sasaki R, Ito N, Shimamura M, Murakami T, Kuzuhara S, Uchino M, Uyama E. A novel CLCN1 mutation: P480T in a Japanese family with Thomsen's myotonia congenita. Muscle Nerve. March 2001;24(3):357-63.


[1605] Panel 5 Islet Summary: Ag5938 Expression of the CG59432-01 is restricted to a sample from small intestine (CT=31.6). Thus, expression of this gene could be used to differentiate between this sample and other samples on this panel and as a marker for this tissue.


[1606] AT. CG59383-01: D6MM5E


[1607] Expression of gene CG59383-01 was assessed using the primer-probe set Ag3427, described in Table ATA. Results of the RTQ-PCR runs are shown in Tables ATB, ATC and ATD.


[1608] Table AJTA. Probe Name Ag3427
839TABLE ATAProbe Name Ag3427StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-cagtggaacagaccaagaaca-3′21784532ProbeTET-5′-tctttcttcacagtgtttcagcaaca-3′-TAMRA26817533Reverse5′-ggattatctctgggtctggaa-3′21844534


[1609]

840





TABLE ATB










CNS_neurodegeneration_v1.0











Rel. Exp. (%)

Rel. Exp. (%)



Ag3427, Run

Ag3427, Run


Tissue Name
210351187
Tissue Name
210351187













AD 1 Hippo
11.4
Control (Path) 3
2.0




Temporal Ctx


AD 2 Hippo
50.3
Control (Path) 4
23.3




Temporal Ctx


AD 3 Hippo
10.2
AD 1 Occipital Ctx
9.8


AD 4 Hippo
17.6
AD 2 Occipital Ctx
0.0




(Missing)


AD 5 Hippo
59.5
AD 3 Occipital Ctx
0.0


AD 6 Hippo
42.9
AD 4 Occipital Ctx
17.0


Control 2 Hippo
21.2
AD 5 Occipital Ctx
25.3


Control 4 Hippo
6.1
AD 6 Occipital Ctx
29.9


Control (Path) 3
15.1
Control 1 Occipital
3.0


Hippo

Ctx


AD 1 Temporal
22.7
Control 2 Occipital
32.3


Ctx

Ctx


AD 2 Temporal
45.1
Control 3 Occipital
26.2


Ctx

Ctx


AD 3 Temporal
6.0
Control 4 Occipital
8.4


Ctx

Ctx


AD 4 Temporal
39.0
Control (Path) 1
84.1


Ctx

Occipital Ctx


AD 5 Inf
100.0
Control (Path) 2
11.7


Temporal Ctx

Occipital Ctx


AD 5 Sup
53.6
Control (Path) 3
0.9


Temporal Ctx

Occipital Ctx


AD 6 Inf
57.0
Control (Path) 4
10.3


Temporal Ctx

Occipital Ctx


AD 6 Sup
58.2
Control 1 Parietal
6.4


Temporal Ctx

Ctx


Control 1
18.8
Control 2 Parietal
48.6


Temporal Ctx

Ctx


Control 2
51.1
Control 3 Parietal
38.7


Temporal Ctx

Ctx


Control 3
16.5
Control (Path) 1
54.7


Temporal Ctx

Parietal Ctx


Control 3
5.5
Control (Path) 2
8.4


Temporal Ctx

Parietal Ctx


Control (Path) 1
82.9
Control (Path) 3
1.4


Temporal Ctx

Parietal Ctx


Control (Path) 2
33.0
Control (Path) 4
16.2


Temporal Ctx

Parietal Ctx










[1610]

841





TABLE ATC










General_screening_panel_v1.4











Rel. Exp. (%)

Rel. Exp. (%)



Ag3427, Run

Ag3427, Run


Tissue Name
216821480
Tissue Name
216821480













Adipose
0.5
Renal ca. TK-10
8.4


Melanoma* Hs688(A).T
0.0
Bladder
1.7


Melanoma*
0.1
Gastric ca. (liver met.)
0.0


Hs688(B).T

NCI-N87


Melanoma* M14
0.2
Gastric ca. KATO III
0.3


Melanoma*
0.0
Colon ca. SW-948
0.0


LOXIMVI


Melanoma* SK-
0.2
Colon ca. SW480
0.4


MEL-5


Squamous cell
14.5
Colon ca.* (SW480
0.1


carcinoma SCC-4

met) SW620


Testis Pool
10.7
Colon ca. HT29
0.0


Prostate ca.* (bone
0.0
Colon ca. HCT-116
100.0


met) PC-3


Prostate Pool
0.0
Colon ca. CaCo-2
0.1


Placenta
0.2
Colon cancer tissue
1.0


Uterus Pool
0.0
Colon ca. SW1116
0.0


Ovarian ca.
2.9
Colon ca. Colo-205
0.0


OVCAR-3


Ovarian ca. SK-OV-3
50.7
Colon ca. SW-48
0.0


Ovarian ca.
2.1
Colon Pool
0.4


OVCAR-4


Ovarian ca.
1.1
Small Intestine Pool
0.3


OVCAR-5


Ovarian ca.
9.7
Stomach Pool
0.9


IGROV-1


Ovarian ca.
13.7
Bone Marrow Pool
0.4


OVCAR-8


Ovary
0.2
Fetal Heart
0.0


Breast ca. MCF-7
0.1
Heart Pool
0.0


Breast ca. MDA-
0.0
Lymph Node Pool
0.4


MB-231


Breast ca. BT 549
0.0
Fetal Skeletal Muscle
0.2


Breast ca. T47D
2.1
Skeletal Muscle Pool
0.0


Breast ca. MDA-N
0.0
Spleen Pool
0.2


Breast Pool
1.7
Thymus Pool
1.4


Trachea
1.7
CNS cancer
0.0




(glio/astro) U87-MG


Lung
0.0
CNS cancer
0.4




(glio/astro) U-118-MG


Fetal Lung
0.4
CNS cancer
0.1




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.0
CNS cancer (astro) SF-
0.0




539


Lung ca. LX-1
0.3
CNS cancer (astro)
0.8




SNB-75


Lung ca. NCI-H146
0.0
CNS cancer (glio)
13.9




SNB-19


Lung ca. SHP-77
0.0
CNS cancer (glio) SF-
0.0




295


Lung ca. A549
0.0
Brain (Amygdala) Pool
1.7


Lung ca. NCI-H526
0.0
Brain (cerebellum)
0.9


Lung ca. NCI-H23
0.2
Brain (fetal)
0.1


Lung ca. NCI-H460
0.0
Brain (Hippocampus)
2.2




Pool


Lung ca. HOP-62
0.5
Cerebral Cortex Pool
1.7


Lung ca. NCI-H522
0.1
Brain (Substantia nigra) Pool
1.0


Liver
0.0
Brain (Thalamus) Pool
2.9


Fetal Liver
0.1
Brain (whole)
1.7


Liver ca. HepG2
0.0
Spinal Cord Pool
0.2


Kidney Pool
0.2
Adrenal Gland
0.4


Fetal Kidney
0.8
Pituitary gland Pool
1.3


Renal ca. 786-0
0.1
Salivary Gland
0.6


Renal ca. A498
0.1
Thyroid (female)
1.9


Renal ca. ACHN
0.0
Pancreatic ca.
0.1




CAPAN2


Renal ca. UO-31
0.5
Pancreas Pool
2.3










[1611]

842





TABLE ATD










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3427, Run

Ag3427, Run


Tissue Name
166396769
Tissue Name
166396769













Secondary Th1 act
1.4
HUVEC IL-1beta
0.0


Secondary Th2 act
0.0
HUVEC IFN gamma
0.0


Secondary Tr1 act
0.8
HUVEC TNF alpha +
0.0




IFN gamma


Secondary Th1 rest
1.0
HUVEC TNF alpha +
0.0




IL4


Secondary Th2 rest
0.0
HUVEC IL-11
0.0


Secondary Tr1 rest
2.9
Lung Microvascular EC
0.0




none


Primary Th1 act
0.0
Lung Microvascular EC
0.0




TNF alpha + IL-1beta


Primary Th2 act
0.0
Microvascular Dermal
0.0




EC none


Primary Tr1 act
4.9
Microsvasular Dermal
0.0




EC TNF alpha + IL-1beta


Primary Th1 rest
2.5
Bronchial epithelium
7.9




TNF alpha + IL-1beta


Primary Th2 rest
2.0
Small airway epithelium
0.0




none


Primary Tr1 rest
0.6
Small airway epithelium
0.0




TNF alpha + IL-1beta


CD45RA CD4
0.0
Coronery artery SMC rest
0.0


lymphocyte act


CD45RO CD4
0.9
Coronery artery SMC
0.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
0.0
Astrocytes rest
5.0


Secondary CD8
1.0
Astrocytes TNF alpha +
2.4


lymphocyte rest

IL-1beta


Secondary CD8
0.8
KU-812 (Basophil) rest
0.0


lymphocyte act


CD4 lymphocyte none
0.0
KU-812 (Basophil)
0.0




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
2.0
CCD1106
28.5


CD95 CH11

(Keratinocytes) none


LAK cells rest
0.0
CCD1106
100.0




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
0.0
Liver cirrhosis
23.8


LAK cells IL-2 + IL-12
1.6
Lupus kidney
3.4


LAK cells IL-2 + IFN
3.7
NCI-H292 none
1.8


gamma


LAK cells IL-2 + IL-18
0.9
NCI-H292 IL-4
3.8


LAK cells
0.0
NCI-H292 IL-9
2.0


PMA/ionomycin


NK Cells IL-2 rest
0.0
NCI-H292 IL-13
4.0


Two Way MLR 3 day
0.0
NCI-H292 IFN gamma
1.1


Two Way MLR 5 day
0.0
HPAEC none
0.0


Two Way MLR 7 day
0.9
HPAEC TNF alpha + IL-
0.0




1beta


PBMC rest
0.0
Lung fibroblast none
0.0


PBMC PWM
0.7
Lung fibroblast TNF
0.8




alpha + IL-1beta


PBMC PHA-L
0.0
Lung fibroblast IL-4
0.0


Ramos (B cell) none
0.0
Lung fibroblast IL-9
0.7


Ramos (B cell)
0.0
Lung fibroblast IL-13
0.0


ionomycin


B lymphocytes PWM
3.4
Lung fibroblast IFN
0.0




gamma


B lymphocytes CD40L
4.0
Dermal fibroblast
0.9


and IL-4

CCD1070 rest


EOL-1 dbcAMP
0.0
Dermal fibroblast
5.6




CCD1070 TNF alpha


EOL-1 dbcAMP
1.1
Dermal fibroblast
0.0


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
0.0
Dermal fibroblast IFN
0.0




gamma


Dendritic cells LPS
0.0
Dermal fibroblast IL-4
1.6


Dendritic cells anti-
0.0
IBD Colitis 2
5.9


CD40


Monocytes rest
0.0
IBD Crohn's
2.4


Monocytes LPS
0.0
Colon
4.1


Macrophages rest
0.0
Lung
1.7


Macrophages LPS
0.0
Thymus
12.4


HUVEC none
0.0
Kidney
10.2


HUVEC starved
0.0










[1612] CNS_neurodegeneration_v1.0 Summary: Ag3427 This panel confirms the expression of CG59383-01 gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.


[1613] General_screening_panel_v1.4 Summary: Ag3427 Highest expression of the CG59383-01 gene is seen in a colon cancer cell line (CT=27.2). Significant expression is also seen in a cluster of samples derived from ovarian cancer cell lines. Thus, expression of this gene could be used to differentiate between these samples and other samples on this panel and as a marker for the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of ovarian or colon cancers.


[1614] This molecule is also expressed at low levels in all regions of the CNS examined. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.


[1615] Among tissues with metabolic function, this gene is expressed at low levels in adipose and pancreas. This expression suggests that this gene product may play a role in normal neuroendocrine and metabolic and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes


[1616] Panel 4D Summary: Ag3427 Highest expression of the CG59383-01 gene is seen in keratinocytes treated with the inflammatory cytokines TNF-alpha and IL-1 beta (CT=30.3). Therefore, modulation of the expression or activity of the protein encoded by this transcript through the application of small molecule therapeutics may be useful in the treatment of asthma, COPD, emphysema, psoriasis and wound healing.


[1617] AU. CG58526-01: Scramblase


[1618] Expression of gene CG358526-01 was assessed using the primer-probe set Ag3366, described in Table AUA. Results of the RTQ-PCR runs are shown in Table AUB.


[1619] Table AUA. Probe Name Ag3366
843TABLE AUAProbe Name Ag3366StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-tgtcttcacaaatgctgacaat-3′22729535ProbeTET-5′-ttcggaattcatgttcctgcagatct-3′-TAMRA26751536Reverse5′-gatcattgctgctttgactgtt-3′22783537


[1620]

844





TABLE AUB










General_screening_panel_v1.4











Rel. Exp. (%)

Rel. Exp. (%)



Ag3366, Run

Ag3366, Run


Tissue Name
217042585
Tissue Name
217042585













Adipose
0.0
Renal ca. TK-10
0.0


Melanoma* Hs688(A).T
0.0
Bladder
0.0


Melanoma*
0.0
Gastric ca. (liver met.)
0.0


Hs688(B).T

NCI-N87


Melanoma* M14
0.0
Gastric ca. KATO III
0.0


Melanoma*
0.0
Colon ca. SW-948
0.0


LOXIMVI


Melanoma* SK-MEL-5
0.0
Colon ca. SW480
0.0


Squamous cell
0.0
Colon ca.* (SW480
100.0


carcinoma SCC-4

met) SW620


Testis Pool
69.3
Colon ca. HT29
0.0


Prostate ca.* (bone
0.0
Colon ca. HCT-116
25.2


met) PC-3


Prostate Pool
0.0
Colon ca. CaCo-2
43.2


Placenta
0.0
Colon cancer tissue
0.0


Uterus Pool
0.0
Colon ca. SW1116
0.0


Ovarian ca.
0.0
Colon ca. Colo-205
0.0


OVCAR-3


Ovarian ca. SK-
0.0
Colon ca. SW-48
0.0


OV-3


Ovarian ca.
0.0
Colon Pool
0.0


OVCAR-4


Ovarian ca.
0.0
Small Intestine Pool
0.0


OVCAR-5


Ovarian ca.
0.0
Stomach Pool
49.0


IGROV-1


Ovarian ca.
0.0
Bone Marrow Pool
0.0


OVCAR-8


Ovary
0.0
Fetal Heart
0.0


Breast ca. MCF-7
0.0
Heart Pool
0.0


Breast ca. MDA-
0.0
Lymph Node Pool
0.0


MB-231


Breast ca. BT 549
0.0
Fetal Skeletal Muscle
0.0


Breast ca. T47D
0.0
Skeletal Muscle Pool
0.0


Breast ca. MDA-N
0.0
Spleen Pool
3.9


Breast Pool
0.0
Thymus Pool
0.0


Trachea
0.0
CNS cancer
3.5




(glio/astro) U87-MG


Lung
0.0
CNS cancer
0.0




(glio/astro) U-118-MG


Fetal Lung
0.0
CNS cancer
0.0




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.0
CNS cancer (astro) SF-
0.0




539


Lung ca. LX-1
0.0
CNS cancer (astro)
0.0




SNB-75


Lung ca. NCI-H146
0.0
CNS cancer (glio)
0.0




SNB-19


Lung ca. SHP-77
0.0
CNS cancer (glio) SF-
0.0




295


Lung ca. A549
0.0
Brain (Amygdala) Pool
12.5


Lung ca. NCI-H526
0.0
Brain (cerebellum)
0.0


Lung ca. NCI-H23
0.0
Brain (fetal)
13.8


Lung ca. NCI-H460
0.0
Brain (Hippocampus) Pool
15.0


Lung ca. HOP-62
0.0
Cerebral Cortex Pool
2.6


Lung ca. NCI-H522
0.0
Brain (Substantia
7.5




nigra) Pool


Liver
0.0
Brain (Thalamus) Pool
15.7


Fetal Liver
0.0
Brain (whole)
15.2


Liver ca. HepG2
0.0
Spinal Cord Pool
7.5


Kidney Pool
0.0
Adrenal Gland
0.0


Fetal Kidney
0.0
Pituitary gland Pool
22.8


Renal ca. 786-0
0.0
Salivary Gland
0.0


Renal ca. A498
0.0
Thyroid (female)
0.0


Renal ca. ACHN
0.0
Pancreatic ca.
0.0




CAPAN2


Renal ca. UO-31
0.0
Pancreas Pool
0.0










[1621] CNS_neurodegeneration_v1.0 Summary: Ag3366 Expression of the CG58526-01 gene is low/undetectable in all samples on this panel (CTs>35). (Data not shown.) General_screening_panel_v1.4 Summary: Ag3366 Expression of the CG58526-01 gene is restricted to a sample derived from a colon cancer cell line (CT=34.5) and the testis. Thus, expression of this gene could be used to differentiate between these samples and other samples on this panel and as a marker to detect the presence of colon cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of colon cancer.


[1622] Panel 4D Summary: Ag3366 Results from one experiment with the CG58526-01 gene are not included. The amp plot indicates that there were experimental difficulties with this run.


[1623] AV. CG57851-01: Sulfotransferase


[1624] Expression of gene CG57851-01 was assessed using the primer-probe set Ag3349, described in Table AVA. Results of the RTQ-PCR runs are shown in Tables AVB, AVC and AVD.


[1625] Table AVA. Probe Name Ag3349
845TABLE AVAProbe Name Ag3349StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-acaaaatgatggcgatattgag-3′22237538ProbeTET-5′-cgcttccattcaacttcaacaccct-3′-TAMRA25270539Reverse5′-tcattcttatccactccaggaa-3′22295540


[1626]

846





TABLE AVB










CNS_neurodegeneration_v1.0











Rel. Exp. (%)

Rel. Exp. (%)



Ag3349, Run

Ag3349, Run


Tissue Name
210141483
Tissue Name
210141483













AD 1 Hippo
32.8
Control (Path) 3
0.0




Temporal Ctx


AD 2 Hippo
61.6
Control (Path) 4
48.6




Temporal Ctx


AD 3 Hippo
18.0
AD 1 Occipital
10.5




Ctx


AD 4 Hippo
8.9
AD 2 Occipital
0.0




Ctx (Missing)


AD 5 hippo
18.0
AD 3 Occipital
0.0




Ctx


AD 6 Hippo
11.7
AD 4 Occipital
0.0




Ctx


Control 2 Hippo
27.4
AD 5 Occipital
8.6




Ctx


Control 4 Hippo
17.9
AD 6 Occipital
0.0




Ctx


Control (Path) 3
12.7
Control 1
0.0


Hippo

Occipital Ctx


AD 1 Temporal Ctx
14.8
Control 2
0.0




Occipital Ctx


AD 2 Temporal Ctx
8.7
Control 3
51.4




Occipital Ctx


AD 3 Temporal Ctx
8.2
Control 4
5.6




Occipital Ctx


AD 4 Temporal Ctx
10.4
Control (Path) 1
100.0




Occipital Ctx


AD 5 Inf Temporal
7.2
Control (Path) 2
17.8


Ctx

Occipital Ctx


AD 5 Sup Temporal
7.4
Control (Path) 3
0.0


Ctx

Occipital Ctx


AD 6 Inf Temporal
9.1
Control (Path) 4
41.2


Ctx

Occipital Ctx


AD 6 Sup Temporal
27.9
Control 1 Parietal
3.3


Ctx

Ctx


Control 1 Temporal
9.2
Control 2 Parietal
70.7


Ctx

Ctx


Control 2 Temporal
25.9
Control 3 Parietal
14.3


Ctx

Ctx


Control 3 Temporal
13.4
Control (Path) 1
35.8


Ctx

Parietal Ctx


Control 4 Temporal
3.7
Control (Path) 2
17.7


Ctx

Parietal Ctx


Control (Path) 1
53.2
Control (Path) 3
0.0


Temporal Ctx

Parietal Ctx


Control (Path) 2
51.1
Control (Path) 4
52.1


Temporal Ctx

Parietal Ctx










[1627]

847





TABLE AVC










General_screening_panel_v1.4











Rel. Exp. (%)

Rel. Exp. (%)



Ag3349, Run

Ag3349, Run


Tissue Name
215620671
Tissue Name
215620671













Adipose
3.6
Renal ca. TK-10
1.9


Melanoma* Hs688(A).T
4.5
Bladder
35.4


Melanoma*
0.3
Gastric ca. (liver met.)
0.4


Hs688(B).T

NCI-N87


Melanoma* M14
0.0
Gastric ca. KATO III
0.7


Melanoma*
0.5
Colon ca. SW-948
2.8


LOXIMVI


Melanoma* SK-MEL-5
8.0
Colon ca. SW480
10.2


Squamous cell
0.0
Colon ca.* (SW480
13.5


carcinoma SCC-4

met) SW620


Testis Pool
5.4
Colon ca. HT29
0.0


Prostate ca.* (bone
0.8
Colon ca. HCT-116
0.7


met) PC-3


Prostate Pool
15.1
Colon ca. CaCo-2
3.0


Placenta
0.0
Colon cancer tissue
7.0


Uterus Pool
0.4
Colon ca. SW1116
0.2


Ovarian ca.
0.9
Colon ca. Colo-205
0.8


OVCAR-3


Ovarian ca. SK-
18.4
Colon ca. SW-48
0.0


OV-3


Ovarian ca.
0.0
Colon Pool
5.3


OVCAR-4


Ovarian ca.
10.4
Small Intestine Pool
2.7


OVCAR-5


Ovarian ca.
0.3
Stomach Pool
5.8


IGROV-1


Ovarian ca.
1.3
Bone Marrow Pool
1.7


OVCAR-8


Ovary
5.0
Fetal Heart
2.0


Breast ca. MCF-7
1.0
Heart Pool
2.4


Breast ca. MDA-
1.3
Lymph Node Pool
8.9


MB-231


Breast ca. BT 549
0.4
Fetal Skeletal Muscle
2.7


Breast ca. T47D
9.0
Skeletal Muscle Pool
0.0


Breast ca. MDA-N
1.6
Spleen Pool
0.4


Breast Pool
10.5
Thymus Pool
10.5


Trachea
1.2
CNS cancer
11.4




(glio/astro) U87-MG


Lung
1.3
CNS cancer
2.4




(glio/astro) U-118-MG


Fetal Lung
7.6
CNS cancer
0.1




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.3
CNS cancer (astro) SF-
0.2




539


Lung ca. LX-1
100.0
CNS cancer (astro)
4.6




SNB-75


Lung ca. NCI-H146
0.8
CNS cancer (glio)
3.1




SNB-19


Lung ca. SHP-77
0.0
CNS cancer (glio) SF-
5.3




295


Lung ca. A549
0.8
Brain (Amygdala) Pool
0.4


Lung ca. NCI-H526
0.0
Brain (cerebellum)
0.9


Lung ca. NCI-H23
7.1
Brain (fetal)
1.6


Lung ca. NCI-H460
0.8
Brain (Hippocampus) Pool
0.8


Lung ca. HOP-62
2.6
Cerebral Cortex Pool
2.3


Lung ca. NCI-H522
0.4
Brain (Substantia
2.2




nigra) Pool


Liver
0.0
Brain (Thalamus) Pool
2.8


Fetal Liver
10.5
Brain (whole)
3.1


Liver ca. HepG2
0.8
Spinal Cord Pool
4.1


Kidney Pool
7.9
Adrenal Gland
2.4


Fetal Kidney
47.3
Pituitary gland Pool
1.4


Renal ca. 786-0
2.6
Salivary Gland
1.4


Renal ca. A498
0.9
Thyroid (female)
0.9


Renal ca. ACHN
1.3
Pancreatic ca.
3.7




CAPAN2


Renal ca. UO-31
2.8
Pancreas Pool
9.3










[1628]

848





TABLE AVD










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3349, Run

Ag3349, Run


Tissue Name
165222879
Tissue Name
165222879













Secondary Th1 act
0.0
HUVEC IL-1beta
0.0


Secondary Th2 act
0.0
HUVEC IFN gamma
0.0


Secondary Tr1 act
0.8
HUVEC TNF alpha +
0.0




IFN gamma


Secondary Th1 rest
0.0
HUVEC TNF alpha +
0.0




IL4


Secondary Th2 rest
0.0
HUVEC IL-11
0.0


Secondary Tr1 rest
0.0
Lung Microvascular EC
2.3




none


Primary Th1 act
0.0
Lung Microvascular EC
0.0




TNF alpha + IL-1beta


Primary Th2 act
0.0
Microvascular Dermal
2.3




EC none


Primary Tr1 act
0.0
Microsvasular Dermal
0.6




EC TNF alpha + IL-1beta


Primary Th1 rest
0.0
Bronchial epithelium
0.0




TNF alpha + IL-1beta


Primary Th2 rest
0.7
Small airway epithelium
0.4




none


Primary Tr1 rest
0.0
Small airway epithelium
2.1




TNF alpha + IL-1beta


CD45RA CD4
0.0
Coronery artery SMC rest
0.6


lymphocyte act


CD45RO CD4
0.0
Coronery artery SMC
0.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
0.0
Astrocytes rest
0.0


Secondary CD8
0.0
Astrocytes TNF alpha +
1.0


lymphocyte rest

IL-1beta


Secondary CD8
0.0
KU-812 (Basophil) rest
0.0


lymphocyte act


CD4 lymphocyte none
0.0
KU-812 (Basophil)
0.0




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
0.0
CCD1106
0.6


CD95 CH11

(Keratinocytes) none


LAK cells rest
1.4
CCD1106
0.0




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
0.0
Liver cirrhosis
3.3


LAK cells IL-2 + IL-12
0.0
Lupus kidney
5.8


LAK cells IL-2 + IFN
1.0
NCI-H292 none
0.6


gamma


LAK cells IL-2 + IL-18
0.0
NCI-H292 IL-4
0.0


LAK cells
1.3
NCI-H292 IL-9
1.5


PMA/ionomycin


NK Cells IL-2 rest
0.0
NCI-H292 IL-13
0.8


Two Way MLR 3 day
0.0
NCI-H292 IFN gamma
0.3


Two Way MLR 5 day
0.0
HPAEC none
0.7


Two Way MLR 7 day
1.0
HPAEC TNF alpha + IL-
0.0




1beta


PBMC rest
0.0
Lung fibroblast none
0.0


PBMC PWM
0.0
Lung fibroblast TNF
0.6




alpha + IL-1beta


PBMC PHA-L
0.0
Lung fibroblast IL-4
0.0


Ramos (B cell) none
0.0
Lung fibroblast IL-9
0.9


Ramos (B cell)
0.6
Lung fibroblast IL-13
0.0


ionomycin


B lymphocytes PWM
0.0
Lung fibroblast IFN
0.0




gamma


B lymphocytes CD40L
0.0
Dermal fibroblast
0.6


and IL-4

CCD1070 rest


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.8




CCD1070 TNF alpha


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
7.4
Dermal fibroblast IFN
0.0




gamma


Dendritic cells LPS
2.1
Dermal fibroblast IL-4
0.7


Dendritic cells anti-
2.9
IBD Colitis 2
0.0


CD40


Monocytes rest
0.0
IBD Crohn's
0.0


Monocytes LPS
1.3
Colon
0.6


Macrophages rest
0.9
Lung
0.7


Macrophages LPS
0.2
Thymus
100.0


HUVEC none
0.0
Kidney
1.7


HUVEC starved
0.0










[1629] CNS_neurodegeneration_v1.0 Summary: Ag3349 This panel confirms the expression of CG57851-01 gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. The expression of this gene in the brain suggests that therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.


[1630] General_screening_panel_v1.4 Summary: Ag3349 Highest expression of the CG57851-01 gene is seen in a lung cancer cell line (CT=30). Thus, expression of this gene may be used to differentiate between this sample and other samples on this panel and as a marker for lung cancer. This gene encodes a sulfotransferase homolog. Sulfotransferases are involved in the metabolism of drugs and endogenous compounds in the body and also synthesize the complex glycoproteins found on the cell surface of cancer cells. Therefore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of lung cancer.


[1631] Among tissues with metabolic function, this gene is expressed at moderate to low levels in adipose and pancreas. This expression among these tissues suggests that this gene product may play a role in normal metabolic function and that disregulated expression of this gene may contribute to metabolic diseases, such as obesity and diabetes.


[1632] Panel 4D Summary: Ag3349 Highest expression of the CG57851-01 gene is seen in the thymus (CT=29.7). The putative protein encoded by this gene could therefore play an important role in T cell development. Small molecule therapeutics designed against the protein encoded by this gene could be utilized to modulate immune function (T cell development) and be important for organ transplant, AIDS treatment or post chemotherapy immune reconstitution.


[1633] Panel 5 Islet Summary: Ag3349 Expression of the CG57851-01 gene is low/undetectable in all samples on this panel (CTs>35). (Data not shown.)


[1634] AW. CG59258-01: KIAA1608 Protein


[1635] Expression of gene CG59258-01 was assessed using the primer-probe set Ag3520, described in Table AWA.


[1636] Table AWA. Probe Name Ag3520
849TABLE AWAProbe Name Ag3520StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-cctcacagatgaggacacaga-3′21717541ProbeTET-5′acttgcttgccaaagtcactcagcaa-3′-TAMRA26752542Reverse5′-tttctgagagccagacagacat-3′22781543


[1637] CNS_neurodegeneration_v1.0 Summary: Ag3520 Expression of the CG59258-01 gene is low/undetectable in all samples on this panel (CTs>35). (Data not shown.)


[1638] General_screening_panel_v1.4 Summary: Ag3520 Expression of the CG59258-01 gene is low/undetectable in all samples on this panel (CTs>35). (Data not shown.)


[1639] Panel 4D Summary: Ag3520 Expression of the CG59258-01 gene is low/undetectable in all samples on this panel (CTs>35). (Data not shown.)


[1640] AX. CG59564-01: Sorting Nexin 6


[1641] Expression of gene CG59564-01 was assessed using the primer-probe set Ag3471, described in Table AXA. Results of the RTQ-PCR runs are shown in Tables AXB, AXC and AXD.


[1642] Table AXA. Probe Name Ag3471
850TABLE AXAProbe Name Ag3471StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-gtgcctggcagacgattata-3′20820544ProbeTET-5′-ctatctcagctgcgctgagcagtctg-3′-TAMRA26843545Reverse5′-gtccttagctggttgacttcct-3′22876546


[1643]

851





TABLE AXB










CNS_neurodegeneration_v1.0











Rel. Exp. (%)

Rel. Exp. (%)



Ag3471, Run

Ag3471, Run


Tissue Name
210376963
Tissue Name
210376963













AD 1 Hippo
10.8
Control (Path) 3
2.4




Temporal Ctx


AD 2 Hippo
27.0
Control (Path) 4
28.5




Temporal Ctx


AD 3 Hippo
5.9
AD 1 Occipital Ctx
10.3


AD 4 Hippo
10.8
AD 2 Occipital Ctx
0.0




(Missing)


AD 5 Hippo
64.6
AD 3 Occipital Ctx
3.6


AD 6 Hippo
43.8
AD 4 Occipital Ctx
30.4


Control 2 Hippo
56.3
AD 5 Occipital Ctx
100.0


Control 4 Hippo
4.0
AD 6 Occipital Ctx
14.5


Control (Path) 3
2.3
Control 1 Occipital
1.1


Hippo

Ctx


AD 1 Temporal
11.5
Control 2 Occipital
82.9


Ctx

Ctx


AD 2 Temporal
36.3
Control 3 Occipital
13.3


Ctx

Ctx


AD 3 Temporal
4.7
Control 4 Occipital
5.4


Ctx

Ctx


AD 4 Temporal
27.9
Control (Path) 1
87.7


Ctx

Occipital Ctx


AD 5 Inf
85.9
Control (Path) 2
10.3


Temporal Ctx

Occipital Ctx


AD 5 Sup
37.1
Control (Path) 3
1.5


Temporal Ctx

Occipital Ctx


AD 6 Inf
46.3
Control (Path) 4
12.2


Temporal Ctx

Occipital Ctx


AD 6 Sup
52.1
Control 1 Parietal
3.1


Temporal Ctx

Ctx


Control 1
3.6
Control 2 Parietal
38.4


Temporal Ctx

Ctx


Control 2
81.2
Control 3 Parietal
17.4


Temporal Ctx

Ctx


Control 3
19.1
Control (Path) 1
88.9


Temporal Ctx

Parietal Ctx


Control 3
8.0
Control (Path) 2
22.2


Temporal Ctx

Parietal Ctx


Control (Path) 1
88.9
Control (Path) 3
1.7


Temporal Ctx

Parietal Ctx


Control (Path) 2
48.0
Control (Path) 4
38.7


Temporal Ctx

Parietal Ctx










[1644]

852





TABLE AXC










General_screening_panel_v1.4











Rel. Exp. (%)

Rel. Exp. (%)



Ag3471, Run

Ag3471, Run


Tissue Name
222691297
Tissue Name
222691297













Adipose
2.3
Renal ca. TK-10
2.7


Melanoma* Hs688(A).T
3.1
Bladder
4.2


Melanoma*
4.2
Gastric ca. (liver met.)
6.3


Hs688(B).T

NCI-N87


Melanoma* M14
13.0
Gastric ca. KATO III
4.1


Melanoma*
0.7
Colon ca. SW-948
0.7


LOXIMVI


Melanoma* SK-MEL-5
0.8
Colon ca. SW480
2.6


Squamous cell
1.5
Colon ca.* (SW480
4.5


carcinoma SCC-4

met) SW620


Testis Pool
6.2
Colon ca. HT29
2.2


Prostate ca.* (bone
3.8
Colon ca. HCT-116
3.9


met) PC-3


Prostate Pool
0.7
Colon ca. CaCo-2
3.5


Placenta
2.3
Colon cancer tissue
1.0


Uterus Pool
0.7
Colon ca. SW1116
1.9


Ovarian ca.
5.3
Colon ca. Colo-205
0.6


OVCAR-3


Ovarian ca. SK-
2.1
Colon ca. SW-48
2.3


OV-3


Ovarian ca.
2.8
Colon Pool
7.0


OVCAR-4


Ovarian ca.
5.8
Small Intestine Pool
5.8


OVCAR-5


Ovarian ca.
5.3
Stomach Pool
5.5


IGROV-1


Ovarian ca.
3.0
Bone Marrow Pool
3.5


OVCAR-8


Ovary
7.1
Fetal Heart
1.7


Breast ca. MCF-7
2.2
Heart Pool
3.1


Breast ca. MDA-
2.4
Lymph Node Pool
9.5


MB-231


Breast ca. BT 549
98.6
Fetal Skeletal Muscle
1.4


Breast ca. T47D
8.4
Skeletal Muscle Pool
4.2


Breast ca. MDA-N
4.5
Spleen Pool
1.8


Breast Pool
7.5
Thymus Pool
6.2


Trachea
2.7
CNS cancer
7.0




(glio/astro) U87-MG


Lung
1.9
CNS cancer
4.9




(glio/astro) U-118-MG


Fetal Lung
13.4
CNS cancer
11.3




(neuro; met) SK-N-AS


Lung ca. NCI-N417
2.2
CNS cancer (astro) SF-
1.9




539


Lung ca. LX-1
2.2
CNS cancer (astro)
23.8




SNB-75


Lung ca. NCI-H146
2.1
CNS cancer (glio)
3.6




SNB-19


Lung ca. SHP-77
3.7
CNS cancer (glio) SF-
11.3




295


Lung ca. A549
3.7
Brain (Amygdala) Pool
22.1


Lung ca. NCI-H526
2.5
Brain (cerebellum)
42.9


Lung ca. NCI-H23
17.6
Brain (fetal)
100.0


Lung ca. NCI-H460
1.8
Brain (Hippocampus) Pool
26.6


Lung ca. HOP-62
3.6
Cerebral Cortex Pool
33.0


Lung ca. NCI-H522
5.7
Brain (Substantia
29.3




nigra) Pool


Liver
0.1
Brain (Thalamus) Pool
37.4


Fetal Liver
1.3
Brain (whole)
55.1


Liver ca. HepG2
1.3
Spinal Cord Pool
7.7


Kidney Pool
10.6
Adrenal Gland
1.5


Fetal Kidney
6.7
Pituitary gland Pool
0.6


Renal ca. 786-0
0.9
Salivary Gland
0.8


Renal ca. A498
0.8
Thyroid (female)
0.8


Renal ca. ACHN
2.1
Pancreatic ca.
3.0




CAPAN2


Renal ca. UO-31
3.4
Pancreas Pool
7.4










[1645]

853





TABLE AXD










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3471, Run

Ag3471, Run


Tissue Name
166417126
Tissue Name
166417126













Secondary Th1 act
10.2
HUVEC IL-1beta
2.3


Secondary Th2 act
11.2
HUVEC IFN gamma
7.8


Secondary Tr1 act
19.2
HUVEC TNF alpha +
4.7




IFN gamma


Secondary Th1 rest
28.7
HUVEC TNF alpha +
6.3




IL4


Secondary Th2 rest
18.4
HUVEC IL-11
6.2


Secondary Tr1 rest
24.5
Lung Microvascular EC
6.4




none


Primary Th1 act
8.7
Lung Microvascular EC
7.1




TNF alpha + IL-1beta


Primary Th2 act
20.4
Microvascular Dermal
6.9




EC none


Primary Tr1 act
31.0
Microsvasular Dermal
2.5




EC TNF alpha + IL-1beta


Primary Th1 rest
45.7
Bronchial epithelium
2.6




TNF alpha + IL1beta


Primary Th2 rest
23.3
Small airway epithelium
3.1




none


Primary Tr1 rest
25.3
Small airway epithelium
3.3




TNF alpha + IL-1beta


CD45RA CD4
9.7
Coronery artery SMC rest
3.9


lymphocyte act


CD45RO CD4
23.2
Coronery artery SMC
4.6


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
9.0
Astrocytes rest
12.7


Secondary CD8
24.8
Astrocytes TNF alpha +
18.9


lymphocyte rest

IL-1beta


Secondary CD8
19.9
KU-812 (Basophil) rest
26.2


lymphocyte act


CD4 lymphocyte none
10.6
KU-812 (Basophil)
50.0




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
22.7
CCD1106
6.9


CD95 CH11

(Keratinocytes) none


LAK cells rest
6.4
CCD1106
10.9




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
27.5
Liver cirrhosis
15.3


LAK cells IL-2 + IL-12
21.3
Lupus Kidney
4.2


LAK cells IL-2 + IFN
27.4
NCI-H292 none
5.8


gamma


LAK cells IL-2 + IL-18
22.7
NCI-H292 IL-4
7.2


LAK cells
8.2
NCI-H292 IL-9
3.6


PMA/ionomycin


NK Cells IL-2 rest
13.6
NCI-H292 IL-13
3.7


Two Way MLR 3 day
23.7
NCI-H292 IFN gamma
3.2


Two Way MLR 5 day
5.6
HPAEC none
3.7


Two Way MLR 7 day
7.7
HPAEC TNF alpha + IL-
2.3




1beta


PBMC rest
6.1
Lung fibroblast none
18.3


PBMC PWM
7.3
Lung fibroblast TNF
20.6




alpha + IL-1beta


PBMC PHA-L
7.1
Lung fibroblast IL-4
16.6


Ramos (B cell) none
6.3
Lung fibroblast IL-9
9.2


Ramos (B cell)
3.2
Lung fibroblast IL-13
7.9


ionomycin


B lymphocytes PWM
12.2
Lung fibroblast IFN
6.2




gamma


B lymphocytes CD40L
11.1
Dermal fibroblast
11.4


and IL-4

CCD1070 rest


EOL-1 dbcAMP
7.4
Dermal fibroblast
28.5




CCD1070 TNF alpha


EOL-1 dbcAMP
12.5
Dermal fibroblast
7.2


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
13.4
Dermal fibroblast IFN
6.9




gamma


Dendritic cells LPS
14.0
Dermal Fibroblasts IL-4
12.8


Dendritic cells anti-
15.9
IBD Colitis 2
1.7


CD40


Monocytes rest
21.3
IBD Crohn's
4.8


Monocytes LPS
11.4
Colon
100.0


Macrophages rest
23.5
Lung
12.6


Macrophages LPS
3.7
Thymus
8.9


HUVEC none
6.7
Kidney
34.4


HUVEC starved
11.0










[1646] CNS_neurodegeneration_v1.0 Summary: Ag3471 This panel does not show differential expression of the CG59564-01 gene in Alzheimer's disease. However, this expression profile confirms the presence of this gene in the brain. Please see Panel 1.4 for discussion of utility of this gene in the central nervous system.


[1647] General_screening_panel_v1.4 Summary: Ag3471 The CG59564-01 gene, a sorting nexin homolog, shows highly brain preferential expression. Moderate levels of expression are seen in all brain regions examined, with highest expression in the fetal brain (CT=28.5). Thus, this gene would be useful for distinguishing brain tissue from non-neural tissue, and may be beneficial as a drug target in neurologic disease, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.


[1648] Among tissues with metabolic function, this gene is expressed at low levels in pituitary, adipose, adrenal gland, pancreas, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.


[1649] In addition, this gene is expressed at significant levels in a breast cancer cell line (CT=28.6). Thus, expression of this gene could be used to differentiate this sample from other samples on this panel and as a marker for breast cancer.


[1650] Panel 4D Summary: Ag3471 The CG59564-01 gene, a sorting nexin homolog, is most highly expressed in normal colon (CT=30). In addition, this gene is expressed at high to moderate levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.4 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.


[1651] AY. CG59553-01: Secretory Protein SEC8


[1652] Expression of gene CG59553-01 was assessed using the primer-probe set Ag3465, described in Table AYA. Results of the RTQ-PCR runs are shown in Tables AYB, AYC and AYD.


[1653] Table AYA. Probe Name Ag3465
854TABLE AYAProbe Name Ag3465StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-ttcacagcaagaagatgaacct-3′22616547ProbeTET-5′-tcatagatgaactacaccggcacctg-3′-TAMRA26649548Reverse5′-ctcggctagtcgatttgatgt-3′21676549


[1654]

855





TABLE AYB










CNS_neurodegeneration_v1.0











Rel. Exp. (%)

Rel. Exp. (%)



Ag3465, Run

Ag3465, Run


Tissue Name
210376516
Tissue Name
210376516













AD 1 Hippo
21.3
Control (Path) 3
8.2




Temporal Ctx


AD 2 Hippo
33.0
Control (Path) 4
40.9




Temporal Ctx


AD 3 Hippo
11.0
AD 1 Occipital Ctx
20.7


AD 4 Hippo
11.6
AD 2 Occipital Ctx
0.0




(Missing)


AD 5 Hippo
87.7
AD 3 Occipital Ctx
10.3


AD 6 Hippo
46.7
AD 4 Occipital Ctx
24.8


Control 2 Hippo
29.7
AD 5 Occipital Ctx
40.6


Control 4 Hippo
20.4
AD 6 Occipital Ctx
25.3


Control (Path) 3
14.2
Control 1 Occipital
6.7


Hippo

Ctx


AD 1 Temporal
21.3
Control 2 Occipital
59.9


Ctx

Ctx


AD 2 Temporal
38.7
Control 3 Occipital
21.8


Ctx

Ctx


AD 3 Temporal
8.2
Control 4 Occipital
11.8


Ctx

Ctx


AD 4 Temporal
30.8
Control (Path) 1
79.6


Ctx

Occipital Ctx


AD 5 Inf
100.0
Control (Path) 2
18.8


Temporal Ctx

Occipital Ctx


AD 5 Sup
58.2
Control (Path) 3
4.0


Temporal Ctx

Occipital Ctx


AD 6 Inf
47.6
Control (Path) 4
25.7


Temporal Ctx

Occipital Ctx


AD 6 Sup
52.1
Control 1 Parietal
14.2


Temporal Ctx

Ctx


Control 1
11.8
Control 2 Parietal
56.6


Temporal Ctx

Ctx


Control 2
42.0
Control 3 Parietal
23.8


Temporal Ctx

Ctx


Control 3
22.8
Control (Path) 1
75.3


Temporal Ctx

Parietal Ctx


Control 3
14.0
Control (Path) 2
29.7


Temporal Ctx

Parietal Ctx


Control (Path) 1
64.6
Control (Path) 3
8.5


Temporal Ctx

Parietal Ctx


Control (Path) 2
47.0
Control (Path) 4
52.9


Temporal Ctx

Parietal Ctx










[1655]

856





TABLE AYC










General_screening_panel_v1.4











Rel. Exp. (%)

Rel. Exp. (%)



Ag3465, Run

Ag3465, Run


Tissue Name
217118990
Tissue Name
217118990













Adipose
13.1
Renal ca. TK-10
60.7


Melanoma* Hs688(A).T
22.5
Bladder
37.9


Melanoma*
30.1
Gastric ca. (liver met.)
42.9


Hs688(B).T

NCI-N87


Melanoma* M14
54.7
Gastric ca. KATO III
48.0


Melanoma*
15.5
Colon ca. SW-948
5.5


LOXIMVI


Melanoma* SK-MEL-5
42.0
Colon ca. SW480
57.4


Squamous cell
8.7
Colon ca.* (SW480
37.4


carcinoma SCC-4

met) SW620


Testis Pool
12.8
Colon ca. HT29
25.0


Prostate ca.* (bone
63.7
Colon ca. HCT-116
28.3


met) PC-3


Prostate Pool
13.0
Colon ca. CaCo-2
46.7


Placenta
7.1
Colon cancer tissue
26.4


Uterus Pool
12.0
Colon ca. SW1116
8.6


Ovarian ca.
37.4
Colon ca. Colo-205
6.9


OVCAR-3


Ovarian ca. SK-
21.5
Colon ca. SW-48
7.5


OV-3


Ovarian ca.
26.1
Colon Pool
21.8


OVCAR-4


Ovarian ca.
42.0
Small Intestine Pool
25.5


OVCAR-5


Ovarian ca.
23.5
Stomach Pool
15.4


IGROV-1


Ovarian ca.
24.7
Bone Marrow Pool
9.4


OVCAR-8


Ovary
14.0
Fetal Heart
6.9


Breast ca. MCF-7
38.4
Heart Pool
11.1


Breast ca. MDA-
49.0
Lymph Node Pool
23.8


MB-231


Breast ca. BT 549
45.4
Fetal Skeletal Muscle
11.9


Breast ca. T47D
74.7
Skeletal Muscle Pool
26.2


Breast ca. MDA-N
20.4
Spleen Pool
39.2


Breast Pool
22.8
Thymus Pool
39.8


Trachea
15.4
CNS cancer
100.0




(glio/astro) U87-MG


Lung
6.8
CNS cancer
54.7




(glio/astro) U-118-MG


Fetal Lung
41.5
CNS cancer
50.0




(neuro; met) SK-N-AS


Lung ca. NCI-N417
12.2
CNS cancer (astro) SF-
19.3




539


Lung ca. LX-1
26.1
CNS cancer (astro)
75.3




SNB-75


Lung ca. NCI-H146
12.6
CNS cancer (glio)
23.8




SNB-19


Lung ca. SHP-77
33.9
CNS cancer (glio) SF-
95.3




295


Lung ca. A549
43.8
Brain (Amygdala) Pool
11.6


Lung ca. NCI-H526
7.6
Brain (cerebellum)
12.2


Lung ca. NCI-H23
78.5
Brain (fetal)
32.5


Lung ca. NCI-H460
25.0
Brain (Hippocampus) Pool
12.7


Lung ca. HOP-62
28.5
Cerebral Cortex Pool
15.8


Lung ca. NCI-H522
25.0
Brain (Substantia
11.7




nigra) Pool


Liver
2.0
Brain (Thalamus) Pool
17.7


Fetal Liver
18.7
Brain (whole)
15.6


Liver ca. HepG2
15.5
Spinal Cord Pool
12.5


Kidney Pool
36.6
Adrenal Gland
17.7


Fetal Kidney
26.8
Pituitary gland Pool
6.0


Renal ca. 786-0
55.5
Salivary Gland
7.0


Renal ca. A498
19.8
Thyroid (female)
6.6


Renal ca. ACHN
31.0
Pancreatic ca.
40.3




CAPAN2


Renal ca. UO-31
48.0
Pancreas Pool
28.7










[1656]

857





TABLE AYD










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3465, Run

Ag3465, Run


Tissue Name
166417102
Tissue Name
166417102













Secondary Th1 act
22.1
HUVEC IL-1beta
14.6


Secondary Th2 act
33.9
HUVEC IFN gamma
17.8


Secondary Tr1 act
44.4
HUVEC TNF alpha +
10.6




IFN gamma


Secondary Th1 rest
33.4
HUVEC TNF alpha +
8.3




IL4


Secondary Th2 rest
25.0
HUVEC IL-11
8.2


Secondary Tr1 rest
29.7
Lung Microvascular EC
12.3




none


Primary Th1 act
14.3
Lung Microvascular EC
14.8




TNF alpha + IL-1beta


Primary Th2 act
41.2
Microvascular Dermal
15.5




EC none


Primary Tr1 act
46.7
Microsvasular Dermal
14.7




EC TNF alpha + IL-1beta


Primary Th1 rest
88.9
Bronchial epithelium
15.5




TNF alpha + IL1beta


Primary Th2 rest
39.2
Small airway epithelium
14.0




none


Primary Tr1 rest
31.0
Small airway epithelium
65.5




TNF alpha + IL-1beta


CD45RA CD4
20.6
Coronery artery SMC rest
18.3


lymphocyte act


CD45RO CD4
29.9
Coronery artery SMC
12.5


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
23.0
Astrocytes rest
28.7


Secondary CD8
24.1
Astrocytes TNF alpha +
31.6


lymphocyte rest

IL-1beta


Secondary CD8
18.7
KU-812 (Basophil) rest
19.8


lymphocyte act


CD4 lymphocyte none
19.5
KU-812 (Basophil)
42.6




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
37.4
CCD1106
21.8


CD95 CH11

(Keratinocytes) none


LAK cells rest
17.1
CCD1106
100.0




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
35.8
Liver cirrhosis
16.5


LAK cells IL-2 + IL-12
32.3
Lupus kidney
23.5


LAK cells IL-2 + IFN
38.4
NCI-H292 none
48.6


gamma


LAK cells IL-2 + IL-18
32.5
NCI-H292 IL-4
45.1


LAK cells
12.0
NCI-H292 IL-9
49.7


PMA/ionomycin


NK Cells IL-2 rest
24.7
NCI-H292 IL-13
26.4


Two Way MLR 3 day
31.4
NCI-H292 IFN gamma
25.3


Two Way MLR 5 day
19.6
HPAEC none
17.9


Two Way MLR 7 day
14.9
HPAEC TNF alpha + IL-
20.2




1beta


PBMC rest
18.4
Lung fibroblast none
39.2


PBMC PWM
18.7
Lung fibroblast TNF
32.8




alpha + IL-1beta


PBMC PHA-L
10.2
Lung fibroblast IL-4
28.3


Ramos (B cell) none
61.6
Lung fibroblast IL-9
20.4


Ramos (B cell)
46.7
Lung fibroblast IL-13
19.5


ionomycin


B lymphocytes PWM
28.1
Lung fibroblast IFN
26.6




gamma


B lymphocytes CD40L
44.8
Dermal fibroblast
26.8


and IL-4

CCD1070 rest


EOL-1 dbcAMP
33.2
Dermal fibroblast
50.7




CCD1070 TNF alpha


EOL-1 dbcAMP
25.5
Dermal fibroblast
18.4


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
30.1
Dermal fibroblast IFN
19.2




gamma


Dendritic cells LPS
19.1
Dermal fibroblast IL-4
34.6


Dendritic cells anti-
33.7
IBD Colitis 2
9.0


CD40


Monocytes rest
25.0
IBD Crohn's
12.4


Monocytes LPS
16.3
Colon
56.3


Macrophages rest
44.4
Lung
16.4


Macrophages LPS
14.4
Thymys
49.3


HUVEC none
20.4
Kidney
52.1


HUVEC starved
37.1










[1657] CNS_neurodegeneration_v1.0 Summary: Ag3465 This panel does not show differential expression of the CG59553-01 gene in Alzheimer's disease. However, this expression profile confirms the presence of this gene in the brain. Please see Panel 1.4 for discussion of utility of this gene in the central nervous system.


[1658] General_screening_panel_v1.4 Summary: Ag3465 Highest expression of the CG59553-01 gene is seen in a brain cancer cell line (CTs=24). Expression of this gene is ubiquitous throughout this panel, with significant levels of expression in clusters of cell lines derived from brain, renal, colon, lung, breast, ovarian, and melanoma cancers. These high levels of expression in all the samples on this panel suggest a role for this gene in cell growth and proliferation.


[1659] This molecule is also expressed at high levels in all regions of the CNS examined. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.


[1660] Among tissues with metabolic function, this gene is expressed at high to moderate levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.


[1661] Panel 4D Summary: Ag3465 The CG59553-01 gene is expressed at high to moderate levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.5 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.


[1662] AZ. CG59435-01 and CG59435-02: Human Nedd1


[1663] Expression of gene CG59435-01 and CG59435-02 was assessed using the primer-probe set Ag3437, described in Table AZA. Results of the RTQ-PCR runs are shown in Tables AZB, AZC and AZD. Please note that CG59435-02 represents a full-length physical clone of the CG59435-01 gene, validating the prediction of the gene sequence.


[1664] Table AZA. Probe Name Ag3437
858TABLE AZAProbe Name Ag3437StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-tggtgctgaaagtggaaatc-3′201536550ProbeTET-5′-cctctccatcatctaaccaaacaaga-3′-TAMRA2615621551Reverse5′-tgggcttcaatttcattctct-3′211611552


[1665]

859





TABLE AZB










CNS_neurodegeneration_v1.0











Rel.

Rel.



Exp. (%)

Exp. (%)



Ag3437,

Ag3437,



Run

Run


Tissue Name
210374394
Tissue Name
210374394













AD 1 Hippo
8.9
Control (Path) 3
6.9




Temporal Ctx


AD 2 Hippo
25.7
Control (Path) 4
27.9




Temporal Ctx


AD 3 Hippo
18.2
AD 1 Occipital
26.6




Ctx


AD 4 Hippo
13.2
AD 2 Occipital
0.0




Ctx (Missing)


AD 5 hippo
52.9
AD 3 Occipital
7.6




Ctx


AD 6 Hippo
100.0
AD 4 Occipital
26.6




Ctx


Control 2 Hippo
26.1
AD 5 Occipital
26.8




Ctx


Control 4 Hippo
26.2
AD 6 Occipital
21.8




Ctx


Control (Path) 3
14.7
Control 1
9.0


Hippo

Occipital Ctx


AD 1 Temporal Ctx
35.8
Control 2
23.5




Occipital Ctx


AD 2 Temporal Ctx
27.7
Control 3
17.8




Occipital Ctx


AD 3 Temporal Ctx
14.6
Control 4
14.6




Occipital Ctx


AD 4 Temporal Ctx
23.3
Control (Path) 1
70.2




Occipital Ctx


AD 5 Inf Temporal
65.5
Control (Path) 2
12.9


Ctx

Occipital Ctx


AD 5 SupTemporal
47.0
Control (Path) 3
4.9


Ctx

Occipital Ctx


AD 6 Inf Temporal
78.5
Control (Path) 4
22.2


Ctx

Occipital Ctx


AD 6 Sup Temporal
92.0
Control 1 Parietal
13.3


Ctx

Ctx


Control 1 Temporal
10.9
Control 2 Parietal
50.0


Ctx

Ctx


Control 2 Temporal
23.5
Control 3 Parietal
13.1


Ctx

Ctx


Control 3 Temporal
17.9
Control (Path) 1
35.4


Ctx

Parietal Ctx


Control 4 Temporal
12.8
Control (Path) 2
26.6


Ctx

Parietal Ctx


Control (Path) 1
37.4
Control (Path) 3
5.4


Temporal Ctx

Parietal Ctx


Control (Path) 2
44.4
Control (Path) 4
29.3


Temporal Ctx

Parietal Ctx










[1666]

860





TABLE AZC










General_screening_panel_v1.4











Rel.

Rel.



Exp. (%)

Exp. (%)



Ag3437,

Ag3437,



Run

Run


Tissue Name
217066730
Tissue Name
217066730













Adipose
10.0
Renal ca. TK-10
24.0


Melanoma*
25.7
Bladder
18.6


Hs688(A).T


Melanoma*
27.5
Gastric ca. (liver met.)
100.0


Hs688(B).T

NCI-N87


Melanoma* M14
34.9
Gastric ca. KATO III
60.3


Melanoma*
31.9
Colon ca. SW-948
9.7


LOXIMVI


Melanoma* SK-
8.7
Colon ca. SW480
61.6


MEL-5


Squamous cell
24.8
Colon ca.* (SW480
46.3


carcinoma SCC-4

met) SW620


Testis Pool
25.9
Colon ca. HT29
22.7


Prostate ca.* (bone
84.1
Colon ca. HCT-116
72.2


met) PC-3


Prostate Pool
12.3
Colon ca. CaCo-2
32.8


Placenta
0.3
Colon cancer tissue
38.2


Uterus Pool
11.4
Colon ca. SW1116
7.5


Ovarian ca.
33.2
Colon ca. Colo-205
6.7


OVCAR-3


Ovarian ca. SK-
92.7
Colon ca. SW-48
7.1


OV-3


Ovarian ca.
9.7
Colon Pool
27.2


OVCAR-4


Ovarian ca.
26.4
Small Intestine Pool
22.8


OVCAR-5


Ovarian ca.
16.5
Stomach Pool
12.3


IGROV-1


Ovarian ca.
6.5
Bone Marrow Pool
13.5


OVCAR-8


Ovary
7.6
Fetal Heart
21.9


Breast ca. MCF-7
24.3
Heart Pool
11.7


Breast ca. MDA-
84.1
Lymph Node Pool
30.4


MB-231


Breast ca. BT 549
68.3
Fetal Skeletal Muscle
15.2


Breast ca. T47D
52.1
Skeletal Muscle Pool
28.5


Breast ca. MDA-N
18.9
Spleen Pool
15.8


Breast Pool
26.6
Thymus Pool
21.2


Trachea
9.2
CNS cancer
14.0




(glio/astro) U87-MG


Lung
4.9
CNS cancer
91.4




(glio/astro) U-118-MG


Fetal Lung
49.0
CNS cancer
55.5




(neuro; met) SK-N-AS


Lung ca. NCI-N417
4.9
CNS cancer (astro)
14.5




SF-539


Lung ca. LX-1
37.4
CNS cancer (astro)
33.0




SNB-75


Lung ca. NCI-H146
6.8
CNS cancer (glio)
12.5




SNB-19


Lung ca. SHP-77
51.4
CNS cancer (glio)
51.4




SF-295


Lung ca. A549
33.9
Brain (Amygdala)
0.0




Pool


Lung ca. NCI-H526
8.4
Brain (cerebellum)
1.5


Lung ca. NCI-H23
34.4
Brain (fetal)
6.2


Lung ca. NCI-H460
98.6
Brain (Hippocampus)
3.0




Pool


Lung ca. HOP-62
15.2
Cerebral Cortex Pool
3.0


Lung ca. NCI-H522
37.9
Brain (Substantia
3.6




nigra) Pool


Liver
0.4
Brain (Thalamus) Pool
3.9


Fetal Liver
26.8
Brain (whole)
1.1


Liver ca. HepG2
11.3
Spinal Cord Pool
5.0


Kidney Pool
23.2
Adrenal Gland
3.3


Fetal Kidney
42.9
Pituitary gland Pool
4.5


Renal ca. 786-0
41.5
Salivary Gland
0.9


Renal ca. A498
12.9
Thyroid (female)
4.2


Renal ca. ACHN
20.2
Pancreatic ca.
20.7




CAPAN2


Renal ca. UO-31
29.7
Pancreas Pool
19.8










[1667]

861





TABLE AZD










Panel 4.1D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3437, Run

Ag3437, Run


Tissue Name
169839068
Tissue Name
169839068













Secondary Th1 act
44.8
HUVEC IL-1beta
23.2


Secondary Th2 act
57.8
HUVEC IFN gamma
26.2


Secondary Tr1 act
60.7
HUVEC TNF alpha +
18.6




IFN gamma


Secondary Th1 rest
10.2
HUVEC TNF alpha +
16.7




IL4


Secondary Th2 rest
14.3
HUVEC IL-11
10.9


Secondary Tr1 rest
13.9
Lung Microvascular EC
28.1




none


Primary Th1 act
37.4
Lung Microvascular EC
25.3




TNF alpha + IL-1beta


Primary Th2 act
34.9
Microvascular Dermal
19.9




EC none


Primary Tr1 act
39.0
Microsvasular Dermal
17.3




EC TNF alpha + IL-1beta


Primary Th1 rest
17.8
Bronchial epithelium
20.9




TNF alpha + IL1beta


Primary Th2 rest
14.7
Small airway epithelium
4.9




none


Primary Tr1 rest
23.2
Small airway epithelium
20.4




TNF alpha + IL-1beta


CD45RA CD4
39.0
Coronery artery SMC rest
10.7


lymphocyte act


CD45RO CD4
37.4
Coronery artery SMC
10.7


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
31.9
Astrocytes rest
9.2


Secondary CD8
33.7
Astrocytes TNF alpha +
6.4


lymphocyte rest

IL-1beta


Secondary CD8
21.8
KU-812 (Basophil) rest
36.6


lymphocyte act


CD4 lymphocyte none
10.4
KU-812 (Basophil)
100.0




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
15.7
CCD1106
21.9


CD95 CH11

(Keratinocytes) none


LAK cells rest
21.8
CCD1106
29.9




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
24.1
Liver cirrhosis
6.0


LAK cells IL-2 + IL-12
33.2
NCI-H292 none
13.0


LAK cells IL-2 + IFN
38.4
NCI-H292 IL-4
25.2


gamma


LAK cells IL-2 + IL-18
33.9
NCI-H292 IL-9
32.8


LAK cells
9.3
NCI-H292 IL-13
26.2


PMA/ionomycin


NK Cells IL-2 rest
27.9
NCI-H292 IFN gamma
37.9


Two Way MLR 3 day
23.2
HPAEC none
13.7


Two Way MLR 5 day
25.3
HPAEC TNF alpha + IL-
30.8




1beta


Two Way MLR 7 day
23.8
Lung fibroblast none
12.1


PBMC rest
9.1
Lung fibroblast TNF
9.5




alpha + IL-1beta


PBMC PWM
25.9
Lung fibroblast IL-4
11.7


PBMC PHA-L
27.7
Lung fibroblast IL-9
19.3


Ramos (B cell) none
23.5
Lung fibroblast IL-13
11.2


Ramos (B cell)
23.0
Lung fibroblast IFN
19.5


ionomycin

gamma


B lymphocytes PWM
36.3
Dermal fibroblast
66.9




CCD1070 rest


B lymphocytes CD40L
21.5
Dermal fibroblast
70.2


and IL-4

CCD1070 TNF alpha


EOL-1 dbcAMP
21.0
Dermal fibroblast
46.3




CCD1070 IL-1beta


EOL-1 dbcAMP
19.8
Dermal fibroblast IFN
17.1


PMA/ionomycin

gamma


Dendritic cells none
10.2
Dermal fibroblast IL-4
21.5


Dendritic cells LPS
10.8
Dermal Fibroblasts rest
8.9


Dendritic cells anti-
9.1
Neutrophils TNFa + LPS
0.5


CD40


Monocytes rest
10.1
Neutrophils rest
5.7


Monocytes LPS
11.6
Colon
5.5


Macrophages rest
13.9
Lung
10.7


Macrophages LPS
15.7
Thymus
39.2


HUVEC none
11.8
Kidney
8.8


HUVEC starved
18.7










[1668] CNS_neurodegeneration_v1.0 Summary: Ag3437 This panel confirms the expression of CG59435-01 gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.


[1669] General_screening_panel_v1.4 Summary: Ag3437 The CG59435-01 is gene is ubiquitously expressed in this panel, with highest expression in a gastric cancer cell line (CT=26.5). In addition, significant levels of expression are evident in cell lines from brain cancer, colon cancer, ovarian cancer, breast cancer, prostate cancer and lung cancer. Thus, expression of this gene could be used as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of these cancers.


[1670] In addition, this gene is expressed at moderate to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among metabolic tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.


[1671] In addition, the CG59435-01 gene encodes a homologue of mouse NEDD1 protein. Nedd is an acronym of “neural precursor cell expressed developmentally and down-regulated” (Ref 1) The developmentally regulated mouse gene Nedd1 encodes a protein with similarities to the beta subunit of heterotrimeric GTP-binding proteins that has growth suppressing activity when overexpressed in various cultured cell types. Neddl mRNA is shown to be strongly expressed in early embryonic brain and may play a role in the differentiation-coupled growth arrest in neuronal cells (Ref. 2). The moderate to low levels (CT=30-0.33) in all regions of the central nervous system examined suggest that this gene product may also play a role in the differentiation-coupled growth arrest in neuronal cells. Furthermore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.



REFERENCES

[1672] 1. Kumar S, Tomooka Y, Noda M. (1992) Identification of a set of genes with developmentally down-regulated expression in the mouse brain. Biochem Biophys Res Commun 185(3):1155-61


[1673] 2. Kumar S, Matsuzaki T, Yoshida Y, Noda M. (1994) Molecular cloning and biological activity of a novel developmentally regulated gene encoding a protein with beta-transducin-like structure. J Biol Chem 269(15):11318-26.


[1674] Panel 4.1D Summary: Ag3437 The CG59435-01 is gene is ubiquitously expressed in this panel, with highest expression in the basophil cell line KU-812 treated with PMA/ionomycin (CT=27.9). This gene is expressed at high to moderate levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.4 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.


[1675] BA. CG59439-01 and CG59439-02: Xenobiotic/Medium-Chain Fatty acid:CoA Ligase Form XL-III


[1676] Expression of gene CG59439-01 was assessed using the primer-probe set Ag3438, described in Table BAA. Results of the RTQ-PCR runs are shown in Table BAB. Please note that CG59439-02 represents a full-length physical clone of the CG59439-01 gene, validating the prediction of the gene sequence.


[1677] Table BAA. Probe Name Ag3438
862TABLE BAAProbe Name Ag3438StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-accccattaaccacttttgg-3′20938553ProbeTET-5′-tcatctatatatcgaatgattctgcagca-3′-TAMRA29964554Reverse5′-gaacctgatgctggtgaaatc-3′21994555


[1678]

863





TABLE BAB










Panel 4.1D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3438, Run

Ag3438, Run


Tissue Name
198383568
Tissue Name
198383568













Secondary Th1 act
4.0
HUVEC IL-1beta
0.0


Secondary Th2 act
100.0
HUVEC IFN gamma
0.0


Secondary Tr1 act
25.9
HUVEC TNF alpha +
0.0




IFN gamma


Secondary Th1 rest
0.0
HUVEC TNF alpha +
0.0




IL4


Secondary Th2 rest
0.0
HUVEC IL-11
0.0


Secondary Tr1 rest
0.0
Lung Microvascular EC
0.0




none


Primary Th1 act
0.0
Lung Microvascular EC
0.0




TNF alpha + IL-1beta


Primary Th2 act
0.0
Microvascular Dermal
0.0




EC none


Primary Tr1 act
0.0
Microsvasular Dermal
0.0




EC TNF alpha + IL-1beta


Primary Th1 rest
0.0
Bronchial epithelium
9.4




TNF alpha + IL1beta


Primary Th2 rest
0.0
Small airway epithelium
7.0




none


Primary Tr1 rest
0.0
Small airway epithelium
13.8




TNF alpha + IL-1beta


CD45RA CD4
16.3
Coronery artery SMC rest
0.0


lymphocyte act


CD45RO CD4
0.0
Coronery artery SMC
0.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
0.0
Astrocytes rest
0.0


Secondary CD8
0.0
Astrocytes TNF alpha +
0.0


lymphocyte rest

IL-1beta


Secondary CD8
0.0
KU-812 (Basophil) rest
25.9


lymphocyte act


CD4 lymphocyte none
12.9
KU-812 (Basophil)
10.5




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
0.0
CCD1106
0.0


CD95 CH11

(Keratinocytes) none


LAK cells rest
6.9
CCD1106
0.0




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
6.1
Liver cirrhosis
20.4


LAK cells IL-2 + IL-12
7.7
NCI-H292 none
0.0


LAK cells IL-2 + IFN
13.6
NCI-H292 IL-4
6.7


gamma


LAK cells IL-2 + IL-18
14.2
NCI-H292 IL-9
11.7


LAK cells
0.0
NCI-H292 IL-13
25.9


PMA/ionomycin


NK Cells IL-2 rest
0.0
NCI-H292 IFN gamma
17.2


Two Way MLR 3 day
14.9
HPAEC none
0.0


Two Way MLR 5 day
0.0
HPAEC TNF alpha + IL-
0.0




1beta


Two Way MLR 7 day
0.0
Lung fibroblast none
0.0


PBMC rest
4.4
Lung fibroblast TNF
0.0




alpha + IL-1beta


PBMC PWM
2.7
Lung fibroblast IL-4
0.0


PBMC PHA-L
21.2
Lung fibroblast IL-9
0.0


Ramos (B cell) none
0.0
Lung fibroblast IL-13
0.0


Ramos (B cell)
0.0
Lung fibroblast IFN
0.0


ionomycin

gamma


B lymphocytes PWM
0.0
Dermal fibroblast
0.0




CCD1070 rest


B lymphocytes CD40L
11.1
Dermal fibroblast
0.0


and IL-4

CCD1070 TNF alpha


EOL-1 dbcAMP
12.2
Dermal fibroblast
0.0




CCD1070 IL-1beta


EOL-1 dbcAMP
0.0
Dermal fibroblast IFN
0.0


PMA/ionomycin

gamma


Dendritic cells none
6.9
Dermal fibroblast IL-4
0.0


Dendritic cells LPS
0.0
Dermal Fibroblasts rest
0.0


Dendritic cells anti-
0.0
Neutrophils TNFa + LPS
0.0


CD40


Monocytes rest
6.4
Neutrophils rest
4.8


Monocytes LPS
0.0
Colon
5.5


Macrophages rest
7.0
Lung
0.0


Macrophages LPS
0.0
Thymus
3.6


HUVEC none
0.0
Kidney
22.4


HUVEC starved
0.0










[1679] CNS_neurodegeneration_v1.0 Summary: Ag3438 Expression of the CG59439-02 gene is low/undetectable in all samples on this panel (CTs>35). (Data not shown.)


[1680] General_screening_panel_v1.4 Summary: Ag3438 Results from one experiment with the CG5;9439-02 gene are not included. The amp plot indicates that there were experimental difficulties with this run.


[1681] Panel 4.1D Summary: Ag3438 Expression of the CG59439-02 gene is restricted to a sample derived from chronically activated Th2 cells (CT=33).


[1682] Panel 41D Summary: Ag3438 Results from one experiment with the CG59439-02 gene are not included. The amp plot indicates that there were experimental difficulties with this run.


[1683] BB. CG59354-01 and CG59354-02 and CG59354-03: Phosducin-Like Protein


[1684] Expression of gene CG59354-01 and variant CG59354-02 was assessed using the primer-probe set Ag3553, described in Table BBA. Results of the RTQ-PCR runs are shown in Tables BBB, BBC and BBD. Please note that CG59354-03 represents a full-length physical clone of the CG59354-01 gene, validating the prediction of the gene sequence.
864TABLE BBAProbe Name Ag3553StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-tctatttccaggtcgctatcct-3′221778556ProbeTET-5′-acgcacagatgtcagcaccaagactt-3′-TAMRA261822557Reverse5′-ggaatttggattactcccagaa-3′221852558


[1685]

865





TABLE BBB










CNS_neurodegeneration_v1.0











Rel.

Rel.



Exp. (%)

Exp. (%)



Ag3553,

Ag3553,



Run

Run


Tissue Name
210641082
Tissue Name
210641082













AD 1 Hippo
11.3
Control (Path) 3
3.7




Temporal Ctx


AD 2 Hippo
17.8
Control (Path) 4
19.6




Temporal Ctx


AD 3 Hippo
4.8
AD 1 Occipital
15.6




Ctx


AD 4 Hippo
4.6
AD 2 Occipital
0.0




Ctx (Missing)


AD 5 hippo
70.2
AD 3 Occipital
4.5




Ctx


AD 6 Hippo
55.5
AD 4 Occipital
12.5




Ctx


Control 2 Hippo
20.3
AD 5 Occipital
28.7




Ctx


Control 4 Hippo
14.5
AD 6 Occipital
32.1




Ctx


Control (Path) 3
7.0
Control 1 Occipital
3.5


Hippo

Ctx


AD 1 Temporal Ctx
15.1
Control 2 Occipital
51.1




Ctx


AD 2 Temporal Ctx
18.8
Control 3 Occipital
14.4




Ctx


AD 3 Temporal Ctx
3.4
Control 4 Occipital
4.7




Ctx


AD 4 Temporal Ctx
11.7
Control (Path) 1
64.6




Occipital Ctx


AD 5 Inf Temporal
100.0
Control (Path) 2
8.0


Ctx

Occipital Ctx


AD 5 SupTemporal
50.7
Control (Path) 3
3.9


Ctx

Occipital Ctx


AD 6 Inf Temporal
69.7
Control (Path) 4
11.8


Ctx

Occipital Ctx


AD 6 Sup Temporal
66.9
Control 1 Parietal
7.0


Ctx

Ctx


Control 1 Temporal
4.8
Control 2 Parietal
41.2


Ctx

Ctx


Control 2 Temporal
26.6
Control 3 Parietal
12.0


Ctx

Ctx


Control 3 Temporal
9.1
Control (Path) 1
62.0


Ctx

Parietal Ctx


Control 4 Temporal
7.5
Control (Path) 2
21.6


Ctx

Parietal Ctx


Control (Path) 1
44.8
Control (Path) 3
3.5


Temporal Ctx

Parietal Ctx


Control (Path) 2
24.8
Control (Path) 4
41.8


Temporal Ctx

Parietal Ctx










[1686]

866





TABLE BBC










General_screening_panel_v1.4











Rel.

Rel.



Exp. (%)

Exp. (%)



Ag3553,

Ag3553,



Run

Run


Tissue Name
217049381
Tissue Name
217049381













Adipose
5.2
Renal ca. TK-10
40.6


Melanoma*
40.3
Bladder
29.9


Hs688(A).T


Melanoma*
31.9
Gastric ca. (liver met.)
39.5


Hs688(B).T

NCI-N87


Melanoma* M14
41.5
Gastric ca. KATO III
55.9


Melanoma*
37.1
Colon ca. SW-948
9.0


LOXIMVI


Melanoma* SK-
25.9
Colon ca. SW480
68.3


MEL-5


Squamous cell
17.9
Colon ca.* (SW480
23.5


carcinoma SCC-4

met) SW620


Testis Pool
5.4
Colon ca. HT29
20.0


Prostate ca.* (bone
31.4
Colon ca. HCT-116
66.0


met) PC-3


Prostate Pool
9.0
Colon ca. CaCo-2
32.8


Placenta
4.0
Colon cancer tissue
17.4


Uterus Pool
5.5
Colon ca. SW1116
4.0


Ovarian ca.
40.1
Colon ca. Colo-205
11.3


OVCAR-3


Ovarian ca. SK-
47.3
Colon ca. SW-48
9.9


OV-3


Ovarian ca.
11.4
Colon Pool
18.4


OVCAR-4


Ovarian ca.
37.9
Small Intestine Pool
11.7


OVCAR-5


Ovarian ca.
25.0
Stomach Pool
14.9


IGROV-1


Ovarian ca.
16.6
Bone Marrow Pool
6.9


OVCAR-8


Ovary
10.2
Fetal Heart
4.6


Breast ca. MCF-7
42.6
Heart Pool
6.6


Breast ca. MDA-
50.7
Lymph Node Pool
21.3


MB-231


Breast ca. BT 549
81.8
Fetal Skeletal Muscle
3.8


Breast ca. T47D
85.9
Skeletal Muscle Pool
6.0


Breast ca. MDA-N
33.0
Spleen Pool
13.9


Breast Pool
17.3
Thymus Pool
11.1


Trachea
16.4
CNS cancer
44.4




(glio/astro) U87-MG


Lung
5.3
CNS cancer
45.4




(glio/astro) U-118-MG


Fetal Lung
33.7
CNS cancer
44.8




(neuro; met) SK-N-AS


Lung ca. NCI-N417
5.8
CNS cancer (astro)
31.0




SF-539


Lung ca. LX-1
22.7
CNS cancer (astro)
100.0




SNB-75


Lung ca. NCI-H146
16.7
CNS cancer (glio)
27.4




SNB-19


Lung ca. SHP-77
59.5
CNS cancer (glio)
59.5




SF-295


Lung ca. A549
41.5
Brain (Amygdala)
8.3




Pool


Lung ca. NCI-H526
5.4
Brain (cerebellum)
8.0


Lung ca. NCI-H23
31.0
Brain (fetal)
23.8


Lung ca. NCI-H460
33.4
Brain (Hippocampus)
10.7




Pool


Lung ca. HOP-62
21.9
Cerebral Cortex Pool
15.1


Lung ca. NCI-H522
17.8
Brain (Substantia
11.0




nigra) Pool


Liver
0.5
Brain (Thalamus) Pool
16.6


Fetal Liver
18.3
Brain (whole)
11.8


Liver ca. HepG2
9.2
Spinal Cord Pool
11.7


Kidney Pool
29.5
Adrenal Gland
6.5


Fetal Kidney
16.2
Pituitary gland Pool
4.7


Renal ca. 786-0
57.0
Salivary Gland
9.2


Renal ca. A498
7.9
Thyroid (female)
8.3


Renal ca. ACHN
20.9
Pancreatic ca.
30.4




CAPAN2


Renal ca. UO-31
29.1
Pancreas Pool
21.3










[1687]

867





TABLE BBD










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3553, Run

Ag3553, Run


Tissue Name
166487505
Tissue Name
166487505













Secondary Th1 act
45.4
HUVEC IL-1beta
17.0


Secondary Th2 act
42.9
HUVEC IFN gamma
39.2


Secondary Tr1 act
58.6
HUVEC TNF alpha +
27.4




IFN gamma


Secondary Th1 rest
6.7
HUVEC TNF alpha +
31.4




IL4


Secondary Th2 rest
14.5
HUVEC IL-11
23.7


Secondary Tr1 rest
15.0
Lung Microvascular EC
41.2




none


Primary Th1 act
38.4
Lung Microvascular EC
28.3




TNF alpha + IL-1beta


Primary Th2 act
24.5
Microvascular Dermal
59.0




EC none


Primary Tr1 act
32.8
Microsvasular Dermal
23.5




EC TNF alpha + IL-1beta


Primary Th1 rest
57.0
Bronchial epithelium
21.5




TNF alpha + IL1beta


Primary Th2 rest
43.2
Small airway epithelium
5.8




none


Primary Tr1 rest
39.0
Small airway epithelium
52.5




TNF alpha + IL-1beta


CD45RA CD4
25.5
Coronery artery SMC rest
14.3


lymphocyte act


CD45RO CD4
34.6
Coronery artery SMC
12.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
28.1
Astrocytes rest
18.2


Secondary CD8
30.8
Astrocytes TNF alpha +
11.3


lymphocyte rest

IL-1beta


Secondary CD8
21.9
KU-812 (Basophil) rest
19.6


lymphocyte act


CD4 lymphocyte none
6.0
KU-812 (Basophil)
71.2




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
21.9
CCD1106
31.6


CD95 CH11

(Keratinocytes) none


LAK cells rest
24.8
CCD1106
9.0




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
32.8
Liver cirrhosis
4.1


LAK cells IL-2 + IL-12
24.0
Lupus kidney
4.0


LAK cells IL-2 + IFN
37.6
NCI-H292 none
35.1


gamma


LAK cells IL-2 + IL-18
27.2
NCI-H292 IL-4
39.2


LAK cells
16.8
NCI-H292 IL-9
49.0


PMA/ionomycin


NK Cells IL-2 rest
23.5
NCI-H292 IL-13
28.7


Two Way MLR 3 day
21.5
NCI-H292 IFN gamma
29.5


Two Way MLR 5 day
16.3
HPAEC none
38.2


Two Way MLR 7 day
17.6
HPAEC TNF alpha + IL-
27.2




1beta


PBMC rest
8.0
Lung fibroblast none
9.4


PBMC PWM
91.4
Lung fibroblast TNF
11.1




alpha + IL-1beta


PBMC PHA-L
33.9
Lung fibroblast IL-4
34.6


Ramos (B cell) none
29.5
Lung fibroblast IL-9
21.3


Ramos (B cell)
85.3
Lung fibroblast IL-13
15.8


ionomycin


B lymphocytes PWM
100.0
Lung fibroblast IFN
39.2




gamma


B lymphocytes CD40L
33.0
Dermal fibroblast
45.1


and IL-4

CCD1070 rest


EOL-1 dbcAMP
35.8
Dermal fibroblast
75.3




CCD1070 TNF alpha


EOL-1 dbcAMP
46.7
Dermal fibroblast
37.4


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
14.3
Dermal fibroblast IFN
15.7




gamma


Dendritic cells LPS
15.2
Dermal fibroblast IL-4
25.9


Dendritic cells anti-
22.2
IBD Colitis 2
1.4


CD40


Monocytes rest
10.4
IBD Crohn's
1.5


Monocytes LPS
16.7
Colon
16.7


Macrophages rest
27.9
Lung
12.2


Macrophages LPS
5.7
Thymus
28.7


HUVEC none
29.5
Kidney
28.5


HUVEC starved
67.4










[1688] CNS_neurodegeneration_v1.0 Summary: Ag3553 This panel confirms the expression of CG59354-03 gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.


[1689] General_screening_panel_v1.4 Summary: Ag3553 The CG59354-03 gene is ubiquitously expressed in this panel, with highest expression in a brain cancer cell line (CT=25.9). In addition, significant levels of expression are seen in cell lines derived from colon, breast, ovarian, renal, lung, prostate, and melanoma cancers. Furthermore, higher levels of expression are seen in fetal liver and lung (CTs=27-28) when compared to expression in the adult tissues (CTs=30-33). The high levels of expression in fetal tissue and cancer cell lines, both of which are highly proliferative, suggests that this gene product may be involved in cell growth and differentiation. Therefore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of cancer.


[1690] Among tissues with metabolic or endocrine function, this gene is expressed at high to moderate levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases;, such as obesity and diabetes.


[1691] In addition, this gene is expressed at high levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. The CG59354-03 gene encodes a splice variant of phosphoducin-like protein (PHLP). PDCL is a putative modulator of heterotrimeric G proteins. It was initially isolated as the product of an ethanol-responsive gene in neural cell cultures (Ref. 1). PDCL shares extensive amino acid sequence homology with phosducin (PDC), a phosphoprotein expressed in retina and pineal gland that inhibits several G protein-coupled signaling pathways by binding to the beta-gamma subunits, of G proteins. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.



REFERENCES

[1692] 1. Miles M F, Barhite S, Sganga M, Elliott M. (1993) Phosducin-like protein: an ethanol.-responsive potential modulator of guanine nucleotide-binding protein function. Proc Natl Acad Sci USA 90(22):10831-5


[1693] Panel 4D Summary: Ag3553 The CG59354-03 gene is ubiquitously expressed in this panel, with highest expression in B cells treated with polk-weed mitogen (CT=27.2). In addition, this gene is expressd at is expressed at high to moderate levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.4 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.


[1694] BC. CG59319-01 and CG59319-02: Phosducin-Like Protein


[1695] Expression of gene CG59319-01 was assessed using the primer-probe set Ag3544, described in Table BCA. Results of the RTQ-PCR runs are shown in Tables BCB and BCC. Please note that CG59319-02 represents a full-length physical clone of the CG59319-01 gene, validating the prediction of the gene sequence.


[1696] Table BCA. Probe Name Ag3544
868TABLE BCAProbe Name Ag3544StartPrimersSequencesLengthPositionSEQ ID NO:Forward5′-tacagatcaagcatcccaatgt-3′22347559ProbeTET-5′-tggttaaccagcatcttagtcttctagca-3′-TAMRA29375560Reverse5′-ttcacgatggctttaacaaatt-3′22423561


[1697]

869





TABLE BCB










General_screening_panel_v1.4











Rel.

Rel.



Exp. (%)

Exp. (%)



Ag3544,

Ag3544,



Run

Run


Tissue Name
217048127
Tissue Name
217048127













Adipose
0.0
Renal ca. TK-10
0.0


Melanoma*
0.0
Bladder
0.0


Hs688(A).T


Melanoma*
0.0
Gastric ca. (liver met.)
0.7


Hs688(B).T

NCI-N87


Melanoma* M14
0.0
Gastric ca. KATO III
0.0


Melanoma*
0.0
Colon ca. SW-948
0.2


LOXIMVI


Melanoma* SK-
0.0
Colon ca. SW480
0.0


MEL-5


Squamous cell
1.4
Colon ca.* (SW480
0.0


carcinoma SCC-4

met) SW620


Testis Pool
100.0
Colon ca. HT29
0.0


Prostate ca.* (bone
0.0
Colon ca. HCT-116
0.3


met) PC-3


Prostate Pool
0.0
Colon ca. CaCo-2
0.0


Placenta
0.0
Colon cancer tissue
0.0


Uterus Pool
0.0
Colon ca. SW1116
0.0


Ovarian ca.
1.2
Colon ca. Colo-205
0.0


OVCAR-3


Ovarian ca. SK-
0.9
Colon ca. SW-48
0.0


OV-3


Ovarian ca.
0.0
Colon Pool
0.0


OVCAR-4


Ovarian ca.
0.0
Small Intestine Pool
0.0


OVCAR-5


Ovarian ca.
0.2
Stomach Pool
0.0


IGROV-1


Ovarian ca.
0.0
Bone Marrow Pool
0.0


OVCAR-8


Ovary
0.0
Fetal Heart
0.0


Breast ca. MCF-7
0.0
Heart Pool
0.0


Breast ca. MDA-
0.2
Lymph Node Pool
0.0


MB-231


Breast ca. BT 549
0.0
Fetal Skeletal Muscle
0.0


Breast ca. T47D
0.3
Skeletal Muscle Pool
0.0


Breast ca. MDA-N
0.0
Spleen Pool
0.0


Breast Pool
0.0
Thymus Pool
0.0


Trachea
0.5
CNS cancer
0.0




(glio/astro) U87-MG


Lung
0.0
CNS cancer
0.0




(glio/astro) U-118-MG


Fetal Lung
0.0
CNS cancer
0.0




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.0
CNS cancer (astro)
0.3




SF-539


Lung ca. LX-1
0.0
CNS cancer (astro)
0.0




SNB-75


Lung ca. NCI-H146
0.0
CNS cancer (glio)
0.0




SNB-19


Lung ca. SHP-77
0.0
CNS cancer (glio)
0.2




SF-295


Lung ca. A549
0.0
Brain (Amygdala)
0.2




Pool


Lung ca. NCI-H526
1.0
Brain (cerebellum)
0.0


Lung ca. NCI-H23
0.0
Brain (fetal)
0.6


Lung ca. NCI-H460
0.0
Brain (Hippocampus)
0.0




Pool


Lung ca. HOP-62
0.0
Cerebral Cortex Pool
0.2


Lung ca. NCI-H522
0.0
Brain (Substantia
0.0




nigra) Pool


Liver
0.0
Brain (Thalamus) Pool
0.0


Fetal Liver
0.0
Brain (whole)
0.0


Liver ca. HepG2
0.0
Spinal Cord Pool
0.0


Kidney Pool
0.0
Adrenal Gland
0.0


Fetal Kidney
0.0
Pituitary gland Pool
0.0


Renal ca. 786-0
1.6
Salivary Gland
0.0


Renal ca. A498
0.0
Thyroid (female)
0.2


Renal ca. ACHN
0.0
Pancreatic ca.
0.0




CAPAN2


Renal ca. UO-31
0.0
Pancreas Pool
0.0










[1698]

870





TABLE BCC










Panel 4.1D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3544, Run

Ag3544, Run


Tissue Name
169850546
Tissue Name
169850546













Secondary Th1 act
0.0
HUVEC IL-1beta
0.0


Secondary Th2 act
0.0
HUVEC IFN gamma
0.0


Secondary Tr1 act
0.0
HUVEC TNF alpha +
0.0




IFN gamma


Secondary Th1 rest
0.0
HUVEC TNF alpha +
0.0




IL4


Secondary Th2 rest
0.0
HUVEC IL-11
0.0


Secondary Tr1 rest
0.0
Lung Microvascular EC
0.0




none


Primary Th1 act
0.0
Lung Microvascular EC
0.0




TNF alpha + IL-1beta


Primary Th2 act
0.0
Microvascular Dermal
0.0




EC none


Primary Tr1 act
0.0
Microsvasular Dermal
0.0




EC TNF alpha + IL-1beta


Primary Th1 rest
2.6
Bronchial epithelium
0.0




TNF alpha + IL-1beta


Primary Th2 rest
0.0
Small airway epithelium
0.0




none


Primary Tr1 rest
0.0
Small airway epithelium
0.0




TNF alpha + IL-1beta


CD45RA CD4
0.0
Coronery artery SMC rest
0.0


lymphocyte act


CD45RO CD4
0.0
Coronery artery SMC
0.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
0.0
Astrocytes rest
0.0


Secondary CD8
0.0
Astrocytes TNF alpha +
0.0


lymphocyte rest

IL-1beta


Secondary CD8
0.0
KU-812 (Basophil) rest
100.0


lymphocyte act


CD4 lymphocyte none
0.0
KU-812 (Basophil)
61.1




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
0.0
CCD1106
0.0


CD95 CH11

(Keratinocytes) none


LAK cells rest
0.0
CCD1106
0.0




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
0.0
Liver cirrhosis
0.0


LAK cells IL-2 + IL-12
0.0
NCI-H292 none
0.0


LAK cells IL-2 + IFN
0.0
NCI-H292 IL-4
0.0


gamma


LAK cells IL-2 + IL-18
0.0
NCI-H292 IL-9
0.0


LAK cells
0.0
NCI-H292 IL-13
0.0


PMA/ionomycin


NK Cells IL-2 rest
0.0
NCI-H292 IFN gamma
0.0


Two Way MLR 3 day
0.0
HPAEC none
0.0


Two Way MLR 5 day
0.0
HPAEC TNF alpha + IL-
0.0




1beta


Two Way MLR 7 day
0.0
Lung fibroblast none
0.0


PBMC rest
0.0
Lung fibroblast TNF
0.0




alpha + IL-1beta


PBMC PWM
0.0
Lung fibroblast IL-4
0.0


PBMC PHA-L
0.0
Lung fibroblast IL-9
0.0


Ramos (B cell) none
0.0
Lung fibroblast IL-13
0.0


Ramos (B cell)
0.0
Lung fibroblast IFN
0.0


ionomycin

gamma


B lymphocytes PWM
0.0
Dermal fibroblast
0.0




CCD1070 rest


B lymphocytes CD40L
0.0
Dermal fibroblast
0.0


and IL-4

CCD1070 TNF alpha


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0




CCD1070 IL-1beta


EOL-1 dbcAMP
0.0
Dermal fibroblast IFN
0.0


PMA/ionomycin

gamma


Dendritic cells none
0.0
Dermal fibroblast IL-4
0.0


Dendritic cells LPS
0.0
Dermal fibroblasts rest
0.0


Dendritic cells anti-
0.0
Neutrophils TNFa + LPS
0.0


CD40


Monocytes rest
0.0
Neutrophils rest
0.0


Monocytes LPS
0.0
Colon
0.0


Macrophages rest
0.0
Lung
0.0


Macrophages LPS
0.0
Thymus
0.0


HUVEC none
0.0
Kidney
0.0


HUVEC starved
0.0










[1699] CNS_neurodegeneration_v1.0 Summary: Ag3544 Expression of the CG59319-02 gene is low/undetectable in all samples on this panel (CTs>35). (Data not shown.)


[1700] General_screening_panel_v1.4 Summary: Ag3544 Expression of the CG59319-02 gene is restricted to a sample derived from the testis (CT=29.8). Thus, expression of this gene could be used to differentiate between this sample and other samples on this panel and as a marker of testicular tissue. Furthermore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of male infertility or hypogonadism.


[1701] Panel 4.1D Summary: Ag3544 Expression of the CG59319-02 gene is restricted to samples derived from the basophil cell line KU-812 (CTs=32). Thus, expression of this gene could be used as a marker of this cell type. Furthermore, the specific pattern of expression of this gene suggests that therapeutic modulation of the expression or function of the protein encoded by this gene may block or inhibit inflammation or tissue damage due to basophil activation in response to asthma, allergies, hypersensitivity reactions, psoriasis, and viral infections.


[1702] BD. CG59576-01: Olfactory Receptor


[1703] Expression of gene CG59576-01 was assessed using the primer-probe set Ag3478, described in Table BDA. Results of the RTQ-PCR runs are shown in Table BDB.


[1704] Table BDA. Probe Name Ag3478
871TABLE BDAProbe Name Ag3478StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-tggaagtgtagccctgatgtac-3′22708562ProbeTET-5′-tgctcttctctgccaagtactccttt-3′-TAMRA26731563Reverse5′-aaacattaggctgatggttgtg-3′22765564


[1705]

872





TABLE BDB










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3478, Run

Ag3478, Run


Tissue Name
166441540
Tissue Name
166441540













Secondary Th1 act
0.0
HUVEC IL-1beta
0.0


Secondary Th2 act
0.0
HUVEC IFN gamma
0.0


Secondary Tr1 act
0.0
HUVEC TNF alpha +
0.0




IFN gamma


Secondary Th1 rest
0.0
HUVEC TNF alpha +
0.0




IL4


Secondary Th2 rest
9.0
HUVEC IL-11
0.0


Secondary Tr1 rest
0.0
Lung Microvascular EC
0.0




none


Primary Th1 act
0.0
Lung Microvascular EC
0.0




TNF alpha + IL-1beta


Primary Th2 act
0.0
Microvascular Dermal
0.0




EC none


Primary Tr1 act
0.0
Microsvasular Dermal
0.0




EC TNF alpha + IL-1beta


Primary Th1 rest
0.0
Bronchial epithelium
0.0




TNF alpha + IL-1beta


Primary Th2 rest
0.0
Small airway epithelium
0.0




none


Primary Tr1 rest
0.0
Small airway epithelium
0.0




TNF alpha + IL-1beta


CD45RA CD4
0.0
Coronery artery SMC rest
0.0


lymphocyte act


CD45RO CD4
0.0
Coronery artery SMC
0.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
0.0
Astrocytes rest
0.0


Secondary CD8
0.0
Astrocytes TNF alpha +
0.0


lymphocyte rest

IL-1beta


Secondary CD8
0.0
KU-812 (Basophil) rest
0.0


lymphocyte act


CD4 lymphocyte none
0.0
KU-812 (Basophil)
4.6




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
2.6
CCD1106
0.0


CD95 CH11

(Keratinocytes) none


LAK cells rest
0.0
CCD1106
0.0




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
0.0
Liver cirrhosis
100.0


LAK cells IL-2 + IL-12
0.0
Lupus kidney
0.0


LAK cells IL-2 + IFN
0.0
NCI-H292 none
0.0


gamma


LAK cells IL-2 + IL-18
0.0
NCI-H292 IL-4
0.0


LAK cells
0.0
NCI-H292 IL-9
0.0


PMA/ionomycin


NK Cells IL-2 rest
0.0
NCI-H292 IL-13
0.0


Two Way MLR 3 day
0.0
NCI-H292 IFN gamma
0.0


Two Way MLR 5 day
0.0
HPAEC none
0.0


Two Way MLR 7 day
0.0
HPAEC TNF alpha + IL-
0.0




1beta


PBMC rest
0.0
Lung fibroblast none
0.0


PBMC PWM
0.0
Lung fibroblast TNF
0.0




alpha + IL-1beta


PBMC PHA-L
0.0
Lung fibroblast IL-4
0.0


Ramos (B cell) none
0.0
Lung fibroblast IL-9
0.0


Ramos (B cell)
0.0
Lung fibroblast IL-13
0.0


ionomycin


B lymphocytes PWM
0.0
Lung fibroblast IFN
0.0




gamma


B lymphocytes CD40L
0.0
Dermal fibroblast
0.0


and IL-4

CCD1070 rest


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0




CCD1070 TNF alpha


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
0.0
Dermal fibroblast IFN
0.0




gamma


Dendritic cells LPS
0.0
Dermal fibroblast IL-4
0.0


Dendritic cells anti-
0.0
IBD Colitis 2
25.7


CD40


Monocytes rest
0.0
IBD Crohn's
24.3


Monocytes LPS
0.0
Colon
5.9


Macrophages rest
0.0
Lung
5.8


Macrophages LPS
0.0
Thymus
5.9


HUVEC none
0.0
Kidney
10.2


HUVEC starved
0.0










[1706] CNS_neurodegeneration_v1.0 Summary: Ag3478 Expression of the CG59576-01 gene is low/undetectable in all samples on this panel (CTs>35). (Data not shown.)


[1707] General_screening_panel_v1.4 Summary: Ag3478 Expression of the CG59576-01 gene is low/undetectable in all samples on this panel (CTs>35). (Data not shown.)


[1708] General_screening_panel_v1.5 Summary: Ag3478 Expression of the CG59576-01 gene is low/undetectable in all samples on this panel (CTs>35). (Data not shown.)


[1709] Panel 4D Summary: Ag3478 Expression of the CG59576-01 gene is restricted to a sample derived from liver cirrhosis (CT=32.3). Furthermore, expression of this gene is not detected in normal liver in Panel 1.4, suggesting that its expression is unique to liver cirrhosis. This gene encodes a putative GPCR; therefore, antibodies or small molecule therapeutics could reduce or inhibit fibrosis that occurs in liver cirrhosis. In addition, antibodies to this putative GPCR could also be used for the diagnosis of liver cirrhosis.


[1710] Panel 5 Islet Summary: Ag3478 Expression of the CG59576-01 gene is low/undetectable in all samples on this panel (CTs>35). (Data not shown.)


[1711] BE. CG59557-01: Olfactory Receptor


[1712] Expression of gene CG59557-01 was assessed using the primer-probe set Ag3470, described in Table BEA. Results of the RTQ-PCR runs are shown in Table BEB.


[1713] Table BEA. Probe Name Ag3470
873TABLE BEAProbe Name Ag3470StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-ccaaccttctcagtgaacagaa-3′22413565ProbeTET-5′-tctctttcataggttgcctcctgca-3′-TAMRA27440566Reverse5′-ccgagtgagtggaagaagtaca-3′22467567


[1714]

874





TABLE BEB










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3470, Run

Ag3470, Run


Tissue Name
166417125
Tissue Name
166417125













Secondary Th1 act
0.0
HUVEC IL-1beta
0.0


Secondary Th2 act
3.2
HUVEC IFN gamma
0.0


Secondary Tr1 act
0.0
HUVEC TNF alpha +
0.0




IFN gamma


Secondary Th1 rest
0.0
HUVEC TNF alpha +
0.0




IL4


Secondary Th2 rest
0.0
HUVEC IL-11
0.0


Secondary Tr1 rest
0.0
Lung Microvascular EC
0.0




none


Primary Th1 act
0.0
Lung Microvascular EC
3.0




TNF alpha + IL-1beta


Primary Th2 act
0.0
Microvascular Dermal
0.0




EC none


Primary Tr1 act
0.0
Microsvasular Dermal
0.0




EC TNF alpha + IL-1beta


Primary Th1 rest
2.8
Bronchial epithelium
0.0




TNF alpha + IL1beta


Primary Th2 rest
0.0
Small airway epithelium
0.0




none


Primary Tr1 rest
0.0
Small airway epithelium
0.0




TNF alpha + IL-1beta


CD45RA CD4
0.0
Coronery artery SMC rest
0.0


lymphocyte act


CD45RO CD4
0.0
Coronery artery SMC
0.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
0.0
Astrocytes rest
0.0


Secondary CD8
0.0
Astrocytes TNF alpha +
0.0


lymphocyte rest

IL-1beta


Secondary CD8
0.0
KU-812 (Basophil) rest
0.0


lymphocyte act


CD4 lymphocyte none
2.9
KU-812 (Basophil)
0.0




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
0.0
CCD1106
0.0


CD95 CH11

(Keratinocytes) none


LAK cells rest
0.0
CCD1106
0.0




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
0.0
Liver cirrhosis
100.0


LAK cells IL-2 + IL-12
0.0
Lupus kidney
2.2


LAK cells IL-2 + IFN
0.0
NCI-H292 none
0.0


gamma


LAK cells IL-2 + IL-18
3.2
NCI-H292 IL-4
0.0


LAK cells
0.0
NCI-H292 IL-9
0.0


PMA/ionomycin


NK Cells IL-2 rest
0.0
NCI-H292 IL-13
0.0


Two Way MLR 3 day
0.0
NCI-H292 IFN gamma
0.0


Two Way MLR 5 day
0.0
HPAEC none
0.0


Two Way MLR 7 day
0.0
HPAEC TNF alpha + IL-
0.0




1beta


PBMC rest
5.8
Lung fibroblast none
0.0


PBMC PWM
2.7
Lung fibroblast TNF
0.0




alpha + IL-1beta


PBMC PHA-L
0.0
Lung fibroblast IL-4
0.0


Ramos (B cell) none
0.0
Lung fibroblast IL-9
0.0


Ramos (B cell)
0.0
Lung fibroblast IL-13
0.0


ionomycin


B lymphocytes PWM
6.5
Lung fibroblast IFN
0.0




gamma


B lymphocytes CD40L
2.2
Dermal fibroblast
0.0


and IL-4

CCD1070 rest


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0




CCD1070 TNF alpha


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
3.2
Dermal fibroblast IFN
0.0




gamma


Dendritic cells LPS
20.9
Dermal fibroblast IL-4
0.0


Dendritic cells anti-
0.0
IBD Colitis 2
19.6


CD40


Monocytes rest
0.0
IBD Crohn's
4.9


Monocytes LPS
6.3
Colon
13.9


Macrophages rest
21.6
Lung
14.8


Macrophages LPS
0.0
Thymus
2.2


HUVEC none
0.0
Kidney
0.0


HUVEC starved
0.0










[1715] CNS_neurodegeneration_v1.0 Summary: Ag3470 Expression of the CG59557-01 gene is low/undetectable in all samples on this panel (CTs>35). (Data not shown.)


[1716] General_screening_panel_v1.4 Summary: Ag3470 Expression of the CG59557-01 gene is low/undetectable in all samples on this panel (CTs>35). (Data not shown.)


[1717] Panel 4D Summary: Ag3470 Expression of the CG59557-01 gene is detected in a liver cirrhosis sample (CT=32.2). Furthermore, expression of this gene is not detected in normal liver in Panel 1.4, suggesting that its expression is unique to liver cirrhosis. This gene encodes a putative GPCR; therefore, antibodies or small molecule therapeutics could reduce or inhibit fibrosis that occurs in liver cirrhosis. In addition, antibodies to this putative GPCR could also be used for the diagnosis of liver cirrhosis.


[1718] BF. CG59555-01: Olfactory Receptor


[1719] Expression of gene CG59555-01 was assessed using the primer-probe set Ag3467, described in Table BFA. Results of the RTQ-PCR runs are shown in Tables BFB, BFC and BFD.


[1720] Table BFA. Probe Name Ag3467
875TABLE BFAProbe Name Ag3467StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-ggcaaggaaagtcattcctaa-3′21953568ProbeTET-5′-tggtgtgacatttgactctccctcct-3′-TAMRA26975569Reverse5′-tggtaccaagattccaggagat-3′221006570


[1721]

876





TABLE BFB










CNS_neurodegeneration_v1.0











Rel.

Rel.



Exp. (%)

Exp. (%)



Ag3467,

Ag3467,



Run

Run


Tissue Name
210376517
Tissue Name
210376517













AD 1 Hippo
4.6
Control (Path) 3
14.8




Temporal Ctx


AD 2 Hippo
29.7
Control (Path) 4
15.2




Temporal Ctx


AD 3 Hippo
10.7
AD 1 Occipital
14.5




Ctx


AD 4 Hippo
28.9
AD 2 Occipital
0.0




Ctx (Missing)


AD 5 hippo
21.6
AD 3 Occipital
14.5




Ctx


AD 6 Hippo
100.0
AD 4 Occipital
14.8




Ctx


Control 2 Hippo
8.8
AD 5 Occipital
13.7




Ctx


Control 4 Hippo
35.6
AD 6 Occipital
10.3




Ctx


Control (Path) 3
21.9
Control 1 Occipital
18.3


Hippo

Ctx


AD 1 Temporal Ctx
28.3
Control 2 Occipital
7.9




Ctx


AD 2 Temporal Ctx
37.4
Control 3 Occipital
16.2




Ctx


AD 3 Temporal Ctx
7.4
Control 4 Occipital
24.0




Ctx


AD 4 Temporal Ctx
28.3
Control (Path) 1
28.3




Occipital Ctx


AD 5 Inf Temporal
19.3
Control (Path) 2
10.1


Ctx

Occipital Ctx


AD 5 Sup Temporal
33.4
Control (Path) 3
12.6


Ctx

Occipital Ctx


AD 6 Inf Temporal
39.8
Control (Path) 4
14.3


Ctx

Occipital Ctx


AD 6 Sup Temporal
83.5
Control 1 Parietal
8.7


Ctx

Ctx


Control 1 Temporal
14.4
Control 2 Parietal
22.2


Ctx

Ctx


Control 2 Temporal
13.6
Control 3 Parietal
9.8


Ctx

Ctx


Control 3 Temporal
11.8
Control (Path) 1
33.2


Ctx

Parietal Ctx


Control 4 Temporal
16.0
Control (Path) 2
12.4


Ctx

Parietal Ctx


Control (Path) 1
24.3
Control (Path) 3
19.6


Temporal Ctx

Parietal Ctx


Control (Path) 2
6.1
Control (Path) 4
12.9


Temporal Ctx

Parietal Ctx










[1722]

877





TABLE BFC










General_screening_panel_v1.4











Rel.

Rel.



Exp. (%)

Exp. (%)



Ag3467,

Ag3467,



Run

Run


Tissue Name
217119371
Tissue Name
217119371













Adipose
11.6
Renal ca. TK-10
14.6


Melanoma*
27.0
Bladder
14.1


Hs688(A).T


Melanoma*
27.9
Gastric ca. (liver met.)
3.2


Hs688(B).T

NCI-N87


Melanoma* M14
11.2
Gastric ca. KATO III
2.1


Melanoma*
0.0
Colon ca. SW-948
0.4


LOXIMVI


Melanoma* SK-
0.0
Colon ca. SW480
12.7


MEL-5


Squamous cell
1.8
Colon ca.* (SW480
10.4


carcinoma SCC-4

met) SW620


Testis Pool
7.0
Colon ca. HT29
1.7


Prostate ca.* (bone
15.2
Colon ca. HCT-116
7.9


met) PC-3


Prostate Pool
9.7
Colon ca. CaCo-2
5.3


Placenta
1.7
Colon cancer tissue
3.6


Uterus Pool
5.1
Colon ca. SW1116
0.4


Ovarian ca.
4.1
Colon ca. Colo-205
0.2


OVCAR-3


Ovarian ca. SK-
16.2
Colon ca. SW-48
0.5


OV-3


Ovarian ca.
5.2
Colon Pool
20.6


OVCAR-4


Ovarian ca.
13.9
Small Intestine Pool
26.8


OVCAR-5


Ovarian ca.
0.0
Stomach Pool
19.5


IGROV-1


Ovarian ca.
9.5
Bone Marrow Pool
16.7


OVCAR-8


Ovary
8.4
Fetal Heart
23.5


Breast ca. MCF-7
0.8
Heart Pool
11.2


Breast ca. MDA-
26.2
Lymph Node Pool
31.9


MB-231


Breast ca. BT 549
0.0
Fetal Skeletal Muscle
7.1


Breast ca. T47D
18.2
Skeletal Muscle Pool
1.8


Breast ca. MDA-N
10.9
Spleen Pool
22.4


Breast Pool
26.6
Thymus Pool
25.9


Trachea
9.5
CNS cancer
0.4




(glio/astro) U87-MG


Lung
12.4
CNS cancer
0.2




(glio/astro) U-118-MG


Fetal Lung
100.0
CNS cancer
0.0




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.0
CNS cancer (astro)
0.0




SF-539


Lung ca. LX-1
11.6
CNS cancer (astro)
1.5




SNB-75


Lung ca. NCI-H146
0.0
CNS cancer (glio)
1.1




SNB-19


Lung ca. SHP-77
0.1
CNS cancer (glio)
20.0




SF-295


Lung ca. A549
3.0
Brain (Amygdala)
1.9




Pool


Lung ca. NCI-H526
0.0
Brain (cerebellum)
1.0


Lung ca. NCI-H23
13.9
Brain (fetal)
2.5


Lung ca. NCI-H460
5.4
Brain (Hippocampus)
0.2




Pool


Lung ca. HOP-62
6.7
Cerebral Cortex Pool
1.3


Lung ca. NCI-H522
0.0
Brain (Substantia
1.6




nigra) Pool


Liver
0.1
Brain (Thalamus) Pool
2.5


Fetal Liver
6.6
Brain (whole)
1.1


Liver ca. HepG2
1.4
Spinal Cord Pool
4.5


Kidney Pool
34.4
Adrenal Gland
6.3


Fetal Kidney
76.3
Pituitary gland Pool
4.5


Renal ca. 786-0
28.1
Salivary Gland
1.8


Renal ca. A498
12.1
Thyroid (female)
13.4


Renal ca. ACHN
23.0
Pancreatic ca.
1.0




CAPAN2


Renal ca. UO-31
25.0
Pancreas Pool
27.2










[1723]

878





TABLE BFD










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3467, Run

Ag3467, Run


Tissue Name
166417105
Tissue Name
166417105













Secondary Th1 act
2.4
HUVEC IL-1beta
1.5


Secondary Th2 act
5.1
HUVEC IFN gamma
18.2


Secondary Tr1 act
7.2
HUVEC TNF alpha +
6.2




IFN gamma


Secondary Th1 rest
18.2
HUVEC TNF alpha +
1.7




IL4


Secondary Th2 rest
14.6
HUVEC IL-11
1.8


Secondary Tr1 rest
22.1
Lung Microvascular EC
0.6




none


Primary Th1 act
1.3
Lung Microvascular EC
0.3




TNF alpha + IL-1beta


Primary Th2 act
9.0
Microvascular Dermal
0.1




EC none


Primary Tr1 act
7.2
Microsvasular Dermal
0.5




EC TNF alpha + IL-1beta


Primary Th1 rest
100.0
Bronchial epithelium
1.5




TNF alpha + IL1beta


Primary Th2 rest
38.7
Small airway epithelium
1.6




none


Primary Tr1 rest
28.1
Small airway epithelium
6.6




TNF alpha + IL-1beta


CD45RA CD4
1.9
Coronery artery SMC rest
4.5


lymphocyte act


CD45RO CD4
8.7
Coronery artery SMC
5.1


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
4.0
Astrocytes rest
0.4


Secondary CD8
7.5
Astrocytes TNF alpha +
1.7


lymphocyte rest

IL-1beta


Secondary CD8
4.7
KU-812 (Basophil) rest
0.7


lymphocyte act


CD4 lymphocyte none
9.3
KU-812 (Basophil)
3.2




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
52.5
CCD1106
1.5


CD95 CH11

(Keratinocytes) none


LAK cells rest
4.6
CCD1106
16.4




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
15.1
Liver cirrhosis
14.6


LAK cells IL-2 + IL-12
6.5
Lupus kidney
37.6


LAK cells IL-2 + IFN
10.9
NCI-H292 none
4.6


gamma


LAK cells IL-2 + IL-18
6.9
NCI-H292 IL-4
5.2


LAK cells
1.1
NCI-H292 IL-9
5.6


PMA/ionomycin


NK Cells IL-2 rest
3.1
NCI-H292 IL-13
2.3


Two Way MLR 3 day
11.0
NCI-H292 IFN gamma
1.5


Two Way MLR 5 day
6.0
HPAEC none
3.6


Two Way MLR 7 day
6.7
HPAEC TNF alpha + IL-
10.5




1beta


PBMC rest
2.6
Lung fibroblast none
15.3


PBMC PWM
4.2
Lung fibroblast TNF
5.9




alpha + IL-1beta


PBMC PHA-L
3.1
Lung fibroblast IL-4
5.6


Ramos (B cell) none
0.0
Lung fibroblast IL-9
5.6


Ramos (B cell)
0.1
Lung fibroblast IL-13
5.1


ionomycin


B lymphocytes PWM
6.0
Lung fibroblast IFN
7.9




gamma


B lymphocytes CD40L
6.5
Dermal fibroblast
4.5


and IL-4

CCD1070 rest


EOL-1 dbcAMP
0.0
Dermal fibroblast
21.6




CCD1070 TNF alpha


EOL-1 dbcAMP
0.0
Dermal fibroblast
2.0


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
0.4
Dermal fibroblast IFN
3.5




gamma


Dendritic cells LPS
0.1
Dermal fibroblast IL-4
6.9


Dendritic cells anti-
0.1
IBD Colitis 2
10.6


CD40


Monocytes rest
1.6
IBD Crohn's
1.8


Monocytes LPS
1.7
Colon
34.9


Macrophages rest
8.4
Lung
6.7


Macrophages LPS
1.2
Thymus
26.8


HUVEC none
2.6
Kidney
11.3


HUVEC starved
2.8










[1724] CNS_neurodegeneration_v1.0 Summary: Ag3467 The CG59555-01 gene encodes a putative GPCR. It is expressed at low to moderate levels in most of the samples used in this panel. This panel confirms the expression of CG59555-01 gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 10.4 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.


[1725] General_screening_panel_v1.4 Summary: Ag3467 The CG59555-01 gene encodes a putative GPCR. It is expressed at low to moderate levels in large number of the samples used in this panel. Highest expression of this gene is detected in fetal lung (CT=28). Interestingly, this gene is expressed at much higher levels in fetal (CT=28) when compared to adult lung (CT=31). Therefore, expression of this gene can be used to distinguish fetal lung from adult lung and from other samples used in this panel. In addition, this gene is also expressed at much higher levels in fetal fetal liver (CT=32) as compared to adult liver (CT=38). Thus, expression of this gene can be used to distinguish fetal liver from adult liver.


[1726] Among tissues with metabolic or endocrine function, this gene is expressed at low to moderate levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases;, such as obesity and diabetes.


[1727] This gene is also expressed at low levels in all regions of the central nervous system examined, including amygdala, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Several neurotransmitter receptors are GPCRs, including the dopamine receptor family, the serotonin receptor family, the GABAB receptor, muscarinic acetylcholine receptors, and others; thus this GPCR may represent a novel neurotransmitter receptor. Targeting various neurotransmitter receptors (dopamine, serotonin) has proven to be an effective therapy in psychiatric illnesses such as schizophrenia, bipolar disorder, and depression. Furthermore, the cerebral cortex and hippocampus are regions of the brain that are known to be involved in Alzheimer's disease, seizure disorders, and in the normal process of memory formation. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[1728] Panel 4D Summary: Ag3467 The CG59555-01 gene encodes a putative GPCR. Highest expression of this gene is detected in resting primary Th1 cells (CT=27). This gene is expressed at moderate levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests; that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.4 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.


[1729] BG. CG59551-01: Olfactory Receptor


[1730] Expression of gene CG59551-01 was assessed using the primer-probe set Ag3463, described in Table BGA. Results of the RTQ-PCR runs are shown in Tables BGB and BGC.


[1731] Table BGA. Probe Name Ag3463
879TABLE BGAProbe Name Ag3463StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-ctatggtttccagatgtttcca-3′2278571Probe5′-tagatgttccagctgcccatctctga-3′-TAMRA26105572Reverse5′-attqtqaqacacaqctqqattt-3′22132573


[1732]

880





TABLE BGB










General_screening_panel_v1.4











Rel.

Rel.



Exp. (%)

Exp. (%)



Ag3463,

Ag3463,



Run

Run


Tissue Name
217067349
Tissue Name
217067349













Adipose
0.0
Renal ca. TK-10
9.0


Melanoma*
0.0
Bladder
11.2


Hs688(A).T


Melanoma*
0.0
Gastric ca. (liver met.)
13.0


Hs688(B).T

NCI-N87


Melanoma* M14
0.0
Gastric ca. KATO III
0.0


Melanoma*
0.0
Colon ca. SW-948
0.0


LOXIMVI


Melanoma* SK-
43.8
Colon ca. SW480
11.6


MEL-5


Squamous cell
0.0
Colon ca.* (SW480
0.0


carcinoma SCC-4

met) SW620


Testis Pool
85.9
Colon ca. HT29
0.0


Prostate ca.* (bone
0.0
Colon ca. HCT-116
10.7


met) PC-3


Prostate Pool
7.2
Colon ca. CaCo-2
12.8


Placenta
12.8
Colon cancer tissue
0.0


Uterus Pool
0.0
Colon ca. SW1116
0.0


Ovarian ca.
0.0
Colon ca. Colo-205
0.0


OVCAR-3


Ovarian ca. SK-
100.0
Colon ca. SW-48
0.0


OV-3


Ovarian ca.
11.9
Colon Pool
12.5


OVCAR-4


Ovarian ca.
11.3
Small Intestine Pool
0.0


OVCAR-5


Ovarian ca.
26.1
Stomach Pool
0.0


IGROV-1


Ovarian ca.
0.0
Bone Marrow Pool
0.0


OVCAR-8


Ovary
0.0
Fetal Heart
0.0


Breast ca. MCF-7
0.0
Heart Pool
0.0


Breast ca. MDA-
0.0
Lymph Node Pool
23.2


MB-231


Breast ca. BT 549
20.3
Fetal Skeletal Muscle
82.9


Breast ca. T47D
0.0
Skeletal Muscle Pool
0.0


Breast ca. MDA-N
31.9
Spleen Pool
0.0


Breast Pool
12.5
Thymus Pool
0.0


Trachea
20.9
CNS cancer
0.0




(glio/astro) U87-MG


Lung
0.0
CNS cancer
24.0




(glio/astro) U-118-MG


Fetal Lung
23.7
CNS cancer
0.0




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.0
CNS cancer (astro)
0.0




SF-539


Lung ca. LX-1
0.0
CNS cancer (astro)
38.2




SNB-75


Lung ca. NCI-H146
0.0
CNS cancer (glio)
0.0




SNB-19


Lung ca. SHP-77
8.8
CNS cancer (glio)
33.2




SF-295


Lung ca. A549
0.0
Brain (Amygdala)
0.0




Pool


Lung ca. NCI-H526
0.0
Brain (cerebellum)
0.0


Lung ca. NCI-H23
57.4
Brain (fetal)
48.6


Lung ca. NCI-H460
31.2
Brain (Hippocampus)
21.3




Pool


Lung ca. HOP-62
0.0
Cerebral Cortex Pool
35.6


Lung ca. NCI-H522
14.4
Brain (Substantia
15.5




nigra) Pool


Liver
0.0
Brain (Thalamus) Pool
14.1


Fetal Liver
0.0
Brain (whole)
0.0


Liver ca. HepG2
5.0
Spinal Cord Pool
29.5


Kidney Pool
37.9
Adrenal Gland
14.8


Fetal Kidney
0.0
Pituitary gland Pool
0.0


Renal ca. 786-0
0.0
Salivary Gland
0.0


Renal ca. A498
0.0
Thyroid (female)
0.0


Renal ca. ACHN
0.0
Pancreatic ca.
0.0




CAPAN2


Renal ca. UO-31
0.0
Pancreas Pool
12.2










[1733]

881





TABLE BGC










Panel 4.1D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3463, Run

Ag3463, Run


Tissue Name
169839351
Tissue Name
169839351













Secondary Th1 act
0.0
HUVEC IL-1beta
0.0


Secondary Th2 act
0.0
HUVEC IFN gamma
0.0


Secondary Tr1 act
1.3
HUVEC TNF alpha +
0.0




IFN gamma


Secondary Th1 rest
2.6
HUVEC TNF alpha +
0.0




IL4


Secondary Th2 rest
0.0
HUVEC IL-11
0.0


Secondary Tr1 rest
0.0
Lung Microvascular EC
0.0




none


Primary Th1 act
0.0
Lung Microvascular EC
0.0




TNF alpha + IL-1beta


Primary Th2 act
0.0
Microvascular Dermal
0.0




EC none


Primary Tr1 act
0.0
Microsvasular Dermal
1.4




EC TNF alpha + IL-1beta


Primary Th1 rest
0.0
Bronchial epithelium
0.6




TNF alpha + IL1beta


Primary Th2 rest
0.0
Small airway epithelium
0.0




none


Primary Tr1 rest
0.0
Small airway epithelium
0.0




TNF alpha + IL-1beta


CD45RA CD4
0.0
Coronery artery SMC rest
0.0


lymphocyte act


CD45RO CD4
0.0
Coronery artery SMC
0.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
0.0
Astrocytes rest
0.0


Secondary CD8
0.0
Astrocytes TNF alpha +
0.0


lymphocyte rest

IL-1beta


Secondary CD8
0.0
KU-812 (Basophil) rest
7.2


lymphocyte act


CD4 lymphocyte none
0.0
KU-812 (Basophil)
100.0




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
0.0
CCD1106
0.0


CD95 CH11

(Keratinocytes) none


LAK cells rest
0.0
CCD1106
1.1




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
0.0
Liver cirrhosis
1.2


LAK cells IL-2 + IL-12
0.0
NCI-H292 none
0.0


LAK cells IL-2 + IFN
0.0
NCI-H292 IL-4
0.0


gamma


LAK cells IL-2 + IL-18
0.0
NCI-H292 IL-9
0.0


LAK cells
0.0
NCI-H292 IL-13
0.0


PMA/ionomycin


NK Cells IL-2 rest
0.0
NCI-H292 IFN gamma
0.0


Two Way MLR 3 day
1.3
HPAEC none
1.2


Two Way MLR 5 day
0.0
HPAEC TNF alpha + IL-
0.0




1beta


Two Way MLR 7 day
0.0
Lung fibroblast none
1.0


PBMC rest
0.0
Lung fibroblast TNF
0.0




alpha + IL-1beta


PBMC PWM
0.0
Lung fibroblast IL-4
0.0


PBMC PHA-L
0.0
Lung fibroblast IL-9
0.0


Ramos (B cell) none
1.3
Lung fibroblast IL-13
0.0


Ramos (B cell)
0.0
Lung fibroblast IFN
0.0


ionomycin

gamma


B lymphocytes PWM
0.0
Dermal fibroblast
0.0




CCD1070 rest


B lymphocytes CD40L
1.2
Dermal fibroblast
0.0


and IL-4

CCD1070 TNF alpha


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0




CCD1070 IL-1beta


EOL-1 dbcAMP
0.0
Dermal fibroblast IFN
0.0


PMA/ionomycin

gamma


Dendritic cells none
6.1
Dermal fibroblast IL-4
0.0


Dendritic cells LPS
0.0
Dermal Fibroblast rest
0.0


Dendritic cells anti-
1.2
Neutrophils TNFa + LPS
0.0


CD40


Monocytes rest
0.0
Neutrophils rest
0.0


Monocytes LPS
0.0
Colon
0.5


Macrophages rest
4.1
Lung
0.0


Macrophages LPS
0.0
Thymus
0.0


HUVEC none
0.0
Kidney
2.3


HUVEC starved
0.0










[1734] CNS_neurodegeneration_v1.0 Summary: Ag3463


[1735] Expression of the CG59551-01 gene is low/undetectable in all the samples on this panel. (Data not shown.)


[1736] General_screening_panel_v1.4 Summary: Ag3463 The CG59551-01 gene encodes a putative GPCR. Highest expression of this gene is detected in an ovarian cancer cell line SK-OV-3 (CT=34). In addition, low expression of this gene is also observed in fetal skeletal muscle (CT=34.4), one of the lung cancer cell line (CT=34.9), and testis (CT=34.3). Thus, expression of this gene can be used to distinguish these sample from other samples used in this panel. In addition, therapeutic modulation of the activity of the GPCR encoded by this gene may be useful in the treatment of ovarian and lung cancer, fertility, hypogonadism, and muscle related diseases.


[1737] Panel 4.1D Summary: Ag3463 The CG59551-01 gene encodes a putative GPCR. Highest expression of this gene is seen in KU-812 cells treated with PMA/ionomycin (CT=30.86). Thus, expression of this gene can be used to distinguish this sample from other samples used in this panel. In addition, expression of this gene is high in KU-812 (basophils) cells treated with PMA/ionomycin (CT=30.86) as compared to resting KU-812 cells (CT=34.66). Therefore, expression of this gene can be used to distinguish resting from PMA/ionomycin treated-basophils. It is known that GPCR-type receptors are important in multiple physiological responses mediated by basophils (ref. 1). Therefore, antibody or small molecule therapies designed with the protein encoded for by this gene could block or inhibit inflammation or tissue damage due to basophil activation in response to asthma, allergies, hypersensitivity reactions, psoriasis, and viral infections.



REFERENCES

[1738] 1. Heinemann A., Hartnell A., Stubbs V. E., Murakami K., Soler D., LaRosa G., Askenase P. W., Williams T. J., Sabroe I. (2000) Basophil responses to chemokines are regulated by both sequential and cooperative receptor signaling. J. Immunol. 165: 7224-7233.


[1739] BH. CG759540-01: Olfactory Receptor


[1740] Expression of gene CG59540-01 was assessed using the primer-probe sets A03460 and Ag 1519, described in Tables BHA and BHB. Results of the RTQ-PCR runs are shown in Tables BHC, BHD and BHE.


[1741] Table BHA. Probe Name Ag3460
882TABLE BHAProbe Name Ag3460StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-tcagtgcagagatggagatctt-3′2297574ProbeTET-5′-tgcatcttctccctgttatatctcttca-3′-TAMRA28126575Reverse5′-gacagatgagtcccatgttcat-3′22171576


[1742] Table BHB. Probe Name Ag1519
883TABLE BHBProbe Name Ag1519StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-cctggccctcataaatctaatt-3′22503577ProbeTET-5′-ctccttctaaggctgcccttctgtgg-3′-TAMRA26525578Reverse5′-acagacagaatttcaccgaaga-3′22571579


[1743]

884





TABLE BHC










Panel 1.2











Rel.

Rel.



Exp. (%)

Exp. (%)



Ag1519,

Ag1519,



Run

Run


Tissue Name
142098791
Tissue Name
142098791













Endothelial cells
0.0
Renal ca. 786-0
32.1


Heart (Fetal)
1.3
Renal ca. A498
10.7


Pancreas
1.5
Renal ca. RXF 393
7.5


Pancreatic ca.
3.6
Renal ca. ACHN
10.2


CAPAN 2


Adrenal Gland
4.7
Renal ca. UO-31
26.8


Thyroid
0.4
Renal ca. TK-10
14.0


Salivary gland
27.7
Liver
7.2


Pituitary gland
0.0
Liver (fetal)
3.5


Brain (fetal)
0.0
Liver ca.
0.9




(hepatoblast) HepG2


Brain (whole)
0.0
Lung
0.0


Brain (amygdala)
0.0
Lung (fetal)
1.3


Brain (cerebellum)
0.0
Lung ca. (small cell)
22.8




LX-1


Brain
0.3
Lung ca. (small cell)
11.5


(hippocampus)

NCI-H69


Brain (thalamus)
0.2
Lung ca. (s. cell var.)
0.0




SHP-77


Cerebral Cortex
0.3
Lung ca. (large
2.3




cell)NCI-H460


Spinal cord
0.0
Lung ca. (non-sm.
5.1




cell) A549


glio/astro U87-MG
0.4
Lung ca. (non-s. cell)
7.7




NCI-H23


glio/astro
0.9
Lung ca. (non-s. cell)
6.8


U-118-MG

HOP-62


astrocytoma
0.0
Lung ca. (non-s. cl)
0.9


SW1783

NCI-H522


neuro*; met SK-N-
0.0
Lung ca. (squam.)
52.1


AS

SW 900


astrocytoma SF-539
0.0
Lung ca. (squam.)
4.1




NCI-H596


astrocytoma
0.0
Mammary gland
11.8


SNB-75


glioma SNB-19
4.0
Breast ca.* (pl. ef)
11.3




MCF-7


glioma U251
0.0
Breast ca.* (pl. ef)
1.4




MDA-MB-231


glioma SF-295
2.8
Breast ca.* (pl. ef)
6.3




T47D


Heart
13.9
Breast ca. BT-549
0.0


Skeletal Muscle
0.2
Breast ca. MDA-N
12.5


Bone marrow
0.7
Ovary
1.5


Thymus
0.0
Ovarian ca.
12.4




OVCAR-3


Spleen
0.7
Ovarian ca.
23.8




OVCAR-4


Lymph node
0.0
Ovarian ca.
38.2




OVCAR-5


Colorectal Tissue
4.5
Ovarian ca.
35.6




OVCAR-8


Stomach
2.6
Ovarian ca. IGROV-1
2.4


Small intestine
2.6
Ovarian ca. (ascites)
11.2




SK-OV-3


Colon ca. SW480
3.1
Uterus
1.7


Colon ca.* SW620
12.3
Placenta
0.8


(SW480 met)


Colon ca. HT29
12.3
Prostate
14.2


Colon ca. HCT-116
14.3
Prostate ca.* (bone
12.6




met) PC-3


Colon ca. CaCo-2
11.5
Testis
0.4


Colon ca. Tissue
5.7
Melanoma
6.5


(ODO3866)

Hs688(A).T


Colon ca.
100.0
Melanoma* (met)
12.2


HCC-2998

Hs688(B).T


Gastric ca.* (liver
15.7
Melanoma UACC-
0.0


met) NCI-N87

62


Bladder
95.3
Melanoma M14
10.3


Trachea
1.0
Melanoma LOX
0.0




IMVI


Kidney
55.9
Melanoma* (met)
0.0




SK-MEL-5


Kidney (fetal)
7.7










[1744]

885





TABLE BHD










Panel 1.3D











Rel. Exp. (%)

Rel. Exp. (%)



Ag1519,

Ag1519,


Tissue Name
Run 165529518
Tissue Name
Run 165529518













Liver adenocarcinoma
0.0
Kidney (fetal)
0.0


Pancreas
38.7
Renal ca. 786-0
8.1


Pancreatic ca. CAPAN 2
7.9
Renal ca. A498
0.0


Adrenal gland
29.9
Renal ca. RXF 393
29.7


Thyroid
26.6
Renal ca. ACHN
13.4


Salivary gland
0.0
Renal ca. UO-31
0.0


Pituitary gland
17.2
Renal ca. TK-10
16.8


Brain (fetal)
0.0
Liver
0.0


Brain (whole)
0.0
Liver (fetal)
27.4


Brain (amygdala)
0.0
Liver ca.
0.0




(hepatoblast) HepG2


Brain (cerebellum)
0.0
Lung
0.0


Brain (hippocampus)
0.0
Lung (fetal)
15.6


Brain (substantia nigra)
0.0
Lung ca. (small cell)
50.7




LX-1


Brain (thalamus)
0.0
Lung ca. (small cell)
0.0




NCI-H69


Cerebral Cortex
0.0
Lung ca. (s. cell var.)
25.0




SHP-77


Spinal cord
0.0
Lung ca. (large
26.1




cell)NCI-H460


glio/astro U87-MG
0.0
Lung ca. (non-sm.
0.0




cell) A549


glio/astro U-118-MG
0.0
Lung ca. (non-s. cell)
0.0




NCI-H23


astrocytoma SW1783
0.0
Lung ca. (non-s. cell)
27.4




HOP-62


neuro*; met SK-N-AS
0.0
Lung ca. (non-s. cl)
0.0




NCI-H522


astrocytoma SF-539
0.0
Lung ca. (squam.)
18.0




SW 900


astrocytoma SNB-75
0.0
Lung ca. (squam.)
0.0




NCI-H596


glioma SNB-19
0.0
Mammary gland
27.0


glioma U251
18.8
Breast ca.* (pl. ef)
27.0




MCF-7


glioma SF-295
0.0
Breast ca.* (pl. ef)
45.7




MDA-MB-231


Heart (fetal)
16.4
Breast ca.* (pl. ef)
13.7




T47D


Heart
0.0
Breast ca. BT-549
0.0


Skeletal muscle (fetal)
0.0
Breast ca. MDA-N
13.8


Skeletal muscle
18.8
Ovary
0.0


Bone marrow
0.0
Ovarian ca.
0.0




OVCAR-3


Thymus
0.0
Ovarian ca.
11.4




OVCAR-4


Spleen
0.0
Ovarian ca.
2.6




OVCAR-5


Lymph node
34.4
Ovarian ca.
12.3




OVCAR-8


Colorectal
100.0
Ovarian ca. IGROV-1
0.0


Stomach
0.0
Ovarian ca.*
33.7




(ascites) SK-OV-3


Small intestine
0.0
Uterus
0.0


Colon ca. SW480
22.8
Placenta
17.6


Colon ca.*
10.0
Prostate
0.0


SW620(SW480 met)


Colon ca. HT29
16.7
Prostate ca.* (bone
0.0




met)PC-3


Colon ca. HCT-116
16.8
Testis
0.0


Colon ca. CaCo-2
15.6
Melanoma
15.1




Hs688(A).T


Colon ca.
28.9
Melanoma* (met)
9.0


tissue(ODO3866)

Hs688(B).T


Colon ca. HCC-2998
31.0
Melanoma UACC-
0.0




62


Gastric ca.* (liver met)
36.6
Melanoma M14
26.2


NCI-N87


Bladder
51.4
Melanoma LOX
0.0




IMVI


Trachea
0.0
Melanoma* (met)
14.1




SK-MEL-5


Kidney
56.3
Adipose
0.0










[1745]

886





TABLE BHE










Panel 2D











Rel. Exp. (%)

Rel. Exp. (%)



Ag1519,

Ag1519,


Tissue Name
Run 145158010
Tissue Name
Run 145158010













Normal Colon
81.8
Kidney Margin
5.0




8120608


CC Well to Mod Diff
6.0
Kidney Cancer
0.0


(ODO3866)

8120613


CC Margin (ODO3866)
7.3
Kidney Margin
1.9




8120614


CC Gr.2 rectosigmoid
5.8
Kidney Cancer
7.6


(ODO3868)

9010320


CC Margin (ODO3868)
0.0
Kidney Margin
5.8




9010321


CC Mod Diff
18.6
Normal Uterus
4.2


(ODO3920)


CC Margin (ODO3920)
10.6
Uterus Cancer
47.3




064011


CC Gr.2 ascend colon
8.2
Normal Thyroid
21.6


(ODO3921)


CC Margin (ODO3921)
4.8
Thyroid Cancer
42.3




064010


CC from Partial
47.6
Thyroid Cancer
20.9


Hepatectomy

A302152


(ODO4309) Mets


Liver Margin
10.4
Thyroid Margin
59.5


(ODO4309)

A302153


Colon mets to lung
12.2
Normal Breast
71.2


(OD04451-01)


Lung Margin (OD04451-
6.5
Breast Cancer
15.7


02)

(OD04566)


Normal Prostate 6546-1
11.6
Breast Cancer
19.9




(OD04590-01)


Prostate Cancer
31.6
Breast Cancer Mets
41.5


(OD04410)

(OD04590-03)


Prostate Margin
25.5
Breast Cancer
33.7


(OD04410)

Metastasis




(OD04655-05)


Prostate Cancer
27.2
Breast Cancer
27.0


(OD04720-01)

064006


Prostate Margin
31.4
Breast Cancer 1024
48.0


(OD04720-02)


Normal Lung 061010
25.2
Breast Cancer
3.3




9100266


Lung Met to Muscle
6.2
Breast Margin
7.8


(ODO4286)

9100265


Muscle Margin
0.0
Breast Cancer
24.8


(ODO4286)

A209073


Lung Malignant Cancer
39.0
Breast Margin
32.3


(OD03126)

A209073


Lung Margin (OD03126)
12.0
Normal Liver
3.5


Lung Cancer (OD04404)
4.9
Liver Cancer 064003
56.6


Lung Margin (OD04404)
27.9
Liver Cancer 1025
7.2


Lung Cancer (OD04565)
11.9
Liver Cancer 1026
1.8


Lung Margin (OD04565)
1.4
Liver Cancer 6004-T
6.0


Lung Cancer (OD04237-
52.5
Liver Tissue 6004-N
0.0


01)


Lung Margin (OD04237-
20.7
Liver Cancer 6005-T
5.6


02)


Ocular Mel Met to Liver
5.6
Liver Tissue 6005-N
0.0


(ODO4310)


Liver Margin
2.2
Normal Bladder
24.0


(ODO4310)


Melanoma Mets to Lung
0.0
Bladder Cancer 1023
3.3


(OD04321)


Lung Margin (OD04321)
24.7
Bladder Cancer
5.7




A302173


Normal Kidney
100.0
Bladder Cancer
2.9




(OD04718-01)


Kidney Ca, Nuclear
34.4
Bladder Normal
0.0


grade 2 (OD04338)

Adjacent (OD04718-




03)


Kidney Margin
54.7
Normal Ovary
3.9


(OD04338)


Kidney Ca Nuclear
81.8
Ovarian Cancer
7.2


grade 1/2 (OD04339)

064008


Kidney Margin
48.3
Ovarian Cancer
38.4


(OD04339)

(OD04768-07)


Kidney Ca, Clear cell
11.0
Ovary Margin
5.1


type (OD04340)

(OD04768-08)


Kidney Margin
56.6
Normal Stomach
11.4


(OD04340)


Kidney Ca, Nuclear
3.4
Gastric Cancer
6.5


grade 3 (OD04348)

9060358


Kidney Margin
43.2
Stomach Margin
0.0


(OD04348)

9060359


Kidney Cancer
11.5
Gastric Cancer
6.7


(OD04622-01)

9060395


Kidney Margin
3.5
Stomach Margin
4.5


(OD04622-03)

9060394


Kidney Cancer
17.8
Gastric Cancer
0.0


(OD04450-01)

9060397


Kidney Margin
42.0
Stomach Margin
6.7


(OD04450-03)

9060396


Kidney Cancer 8120607
0.0
Gastric Cancer
16.6




064005










[1746] CNS_neurodegeneration_v1.0 Summary: Ag3460 Expression of the CG59540-01 gene is low/undetectable (CT values>35) across the samples in this panel.


[1747] General_screening_panel_v1.4 Summary: Ag3460 Expression of the CG59540-01 gene is low/undetectable (CT values>35) across the samples in this panel.


[1748] Panel 1.2 Summary: Ag1519 The expression of the CG59540-01 gene appears to be highest in a sample derived from a colon cancer cell line (HCC-2998) (CT=28.2). In addition, there is substantial expression associated with normal kidney and bladder. Thus, the expression of this gene could be used to distinguish these tissues from other tissues in the panel. In addition there was noted expression clustered in ovarian, renal and colon cancer cell lines. Therefore, therapeutic modulation of this gene, through the use of small molecule drugs, antibodies or protein therapeutics might be of use in the treatment of colon cancer, renal cancer or ovarian cancer.


[1749] Among tissues with metabolic function, there is moderate expression in fetal and adult heart, adrenal, and pancreas. This expression suggests that therapeutic modulation of the expression or function of the protein encoded by this gene may be useful in the treatment of diseases that involve these tissues, including obesity and diabetes.


[1750] In addition, there appears to be higher levels of expression in adult heart (CT=31) when compared to expression in fetal heart (CT=34.4). Thus, expression of this gene could be used to differentiate between adult and fetal heart tissue. Conversely, expression of this gene is higher in fetal lung (CT=34.5) than in adult lung (CT=40). Thus, expression of this gene could also be used to differentiate between adult and fetal lung.


[1751] Panel 1.3D Summary: Ag1519 Significant expression the CG59540-01 gene is limited to a sample derived from colorectal tissue (CT=34.3). Thus, expression of this gene could be used to differentiate between this sample and other samples on this panel, and between coloreclal tissue and other normal or malignant tissues.


[1752] Panel 2D Summary: Ag1519 The expression of the CG59540-01 gene in panel 2 appears to be highest in a samples derived from normal kidney tissue (CT=32). In addition there appears to be substantial difference in expression between normal kidney adjacent to cancer tissue and the cancer tissue itself. Thus, the expression of this gene could be used to distinguish normal kidney tissue from other samples in the panel. In addition, the expression of this gene could be used to distinguish normal kidney from malignant tissue. Moreover, therapeutic modulation of this gene, through the use of small molecule drugs, antibodies or protein therapeutics might be of use in the treatment of kidney cancer.


[1753] Panel 4D Summary: Ag3460 Expression of the CG59540-01 gene is low/undetectable (CT values>35) across the samples in this panel.


[1754] BI. CG59280-01 and CG59280-02: Olfactory Receptor


[1755] Expression of gene CG59280-01 and CG59280-02 was assessed using the primer-probe set Ag3527, described in Table BIA. Results of the RTQ-PCR runs are shown in Table BIB. Please note that CG59280-02 represents a full-length physical clone of the CG59280-01 gene, validating the prediction of the gene sequence.


[1756] Table BIA. Probe Name Ag3527
887TABLE BIAProbe Name Ag3527StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-atggccattgataggtacgtt-3′21361580ProbeTET-5′-catctgtaaccctctccgctacccaa-3′-TAMRA26384581Reverse5′-ccacagagagctgaacacaga-3′21428582


[1757]

888





TABLE BIB










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3527, Run

Ag3527, Run


Tissue Name
166446354
Tissue Name
166446354













Secondary Th1 act
0.0
HUVEC IL-1beta
0.0


Secondary Th2 act
0.0
HUVEC IFN gamma
0.0


Secondary Tr1 act
0.0
HUVEC TNF alpha +
0.0




IFN gamma


Secondary Th1 rest
0.0
HUVEC TNF alpha +
0.0




IL4


Secondary Th2 rest
0.0
HUVEC IL-11
0.0


Secondary Tr1 rest
2.0
Lung Microvascular EC
0.0




none


Primary Th1 act
0.0
Lung Microvascular EC
0.0




TNF alpha + IL-1beta


Primary Th2 act
0.0
Microvascular Dermal
4.2




EC none


Primary Tr1 act
0.0
Microsvasular Dermal
0.0




EC TNF alpha + IL-1beta


Primary Th1 rest
0.0
Bronchial epithelium
4.2




TNF alpha + IL1beta


Primary Th2 rest
0.0
Small airway epithelium
0.0




none


Primary Tr1 rest
0.0
Small airway epithelium
0.0




TNF alpha + IL-1beta


CD45RA CD4
0.0
Coronery artery SMC rest
0.0


lymphocyte act


CD45RO CD4
0.0
Coronery artery SMC
0.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
0.0
Astrocytes rest
0.0


Secondary CD8
0.0
Astrocytes TNF alpha +
0.0


lymphocyte rest

IL-1beta


Secondary CD8
0.0
KU-812 (Basophil) rest
0.0


lymphocyte act


CD4 lymphocyte none
4.4
KU-812 (Basophil)
0.0




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
0.0
CCD1106
0.0


CD95 CH11

(Keratinocytes) none


LAK cells rest
0.0
CCD1106
0.0




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
0.0
Liver cirrhosis
100.0


LAK cells IL-2 + IL-12
0.0
Lupus kidney
0.0


LAK cells IL-2 + IFN
5.1
NCI-H292 none
0.0


gamma


LAK cells IL-2 + IL-18
0.0
NCI-H292 IL-4
0.0


LAK cells
0.0
NCI-H292 IL-9
0.0


PMA/ionomycin


NK Cells IL-2 rest
0.0
NCI-H292 IL-13
0.0


Two Way MLR 3 day
0.0
NCI-H292 IFN gamma
0.0


Two Way MLR 5 day
0.0
HPAEC none
4.5


Two Way MLR 7 day
0.0
HPAEC TNF alpha + IL-
0.0




1beta


PBMC rest
3.1
Lung fibroblast none
0.0


PBMC PWM
0.0
Lung fibroblast TNF
0.0




alpha + IL-1beta


PBMC PHA-L
0.0
Lung fibroblast IL-4
0.0


Ramos (B cell) none
0.0
Lung fibroblast IL-9
0.0


Ramos (B cell)
0.0
Lung fibroblast IL-13
0.0


ionomycin


B lymphocytes PWM
0.0
Lung fibroblast IFN
0.0




gamma


B lymphocytes CD40L
0.0
Dermal fibroblast
0.0


and IL-4

CCD1070 rest


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0




CCD1070 TNF alpha


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
4.5
Dermal fibroblast IFN
0.0




gamma


Dendritic cells LPS
5.3
Dermal fibroblast IL-4
0.0


Dendritic cells anti-
9.9
IBD Colitis 2
10.8


CD40


Monocytes rest
0.0
IBD Crohn's
8.9


Monocytes LPS
27.0
Colon
0.0


Macrophages rest
9.5
Lung
4.6


Macrophages LPS
4.0
Thymus
0.0


HUVEC none
0.0
Kidney
0.0


HUVEC starved
0.0










[1758] CNS_neurodegeneration_v1.0 Summary: Ag3527 Expression of the CG59280-01 gene is low/undetectable (CT values>35) across the samples in this panel. (Data not shown.)


[1759] General_screening_panel_v1.4 Summary: Ag3527 Expression of the CG59280-01 gene is low/undetectable (CT values>35) across the samples in this panel. (Data not shown.) This gene encodes a G protein-coupled receptor (GPCR), a type of cell surface receptor involved in signal transduction. It is most similar to members of the odorant receptor subfamily of GPCRs. Based on analogy to other odorant receptor genes, we predict that expression of this gene may be highest in nasal epithelium, a sample not represented on this panel.


[1760] Panel 4D Summary: Ag3527 Highest expression of the CG59280-01 gene is seen in the liver cirrhosis sample (CT=31.81). Thus, expression of this gene could be used to differentiate between this sample from the other samples on this panel and as a marker to detect the presence of liver cirrhosis. Furthermore, expression of this gene is not detected in normal liver in Panel 1.4, suggesting that its expression is unique to liver cirrhosis. This gene encodes a putative GPCR; therefore, antibodies or small molecule therapeutics could reduce or inhibit fibrosis that occurs in liver cirrhosis. In addition, antibodies to this putative GPCR could also be used for the diagnosis of liver cirrhosis.


[1761] BJ. CG59568-01: GPCR


[1762] Expression of gene CG59568-01 was assessed using the primer-probe set Ag3474, described in Table BJA. Results of the RTQ-PCR runs are shown in Table BJB.


[1763] Table BJA. Probe Name Ag3474
889TABLE BJAProbe Name Ag3474StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-ttacagcaatcaccatggtctt-3′22475760ProbeTET-5′-accttctgtggaccctatgaaactg-3′-TAMRA26510761Reverse5′-gggtgaagtcacaaaagaagtg-3′22537762


[1764]

890





TABLE BJB










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3474, Run

Ag3474, Run


Tissue Name
166417193
Tissue Name
166417193













Secondary Th1 act
7.1
HUVEC IL-1beta
0.0


Secondary Th2 act
0.0
HUVEC IFN gamma
0.0


Secondary Tr1 act
4.2
HUVEC TNF alpha +
0.0




IFN gamma


Secondary Th1 rest
0.0
HUVEC TNF alpha +
0.0




IL4


Secondary Th2 rest
0.0
HUVEC IL-11
0.0


Secondary Tr1 rest
0.0
Lung Microvascular EC
0.0




none


Primary Th1 act
0.0
Lung Microvascular EC
0.0




TNF alpha + IL-1beta


Primary Th2 act
2.2
Microvascular Dermal
0.0




EC none


Primary Tr1 act
0.0
Microsvasular Dermal
0.0




EC TNF alpha + IL-1beta


Primary Th1 rest
3.3
Bronchial epithelium
0.0




TNF alpha + IL1beta


Primary Th2 rest
5.9
Small airway epithelium
0.0




none


Primary Tr1 rest
0.0
Small airway epithelium
0.3




TNF alpha + IL-1beta


CD45RA CD4
0.0
Coronery artery SMC rest
0.0


lymphocyte act


CD45RO CD4
0.0
Coronery artery SMC
0.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
0.0
Astrocytes rest
0.0


Secondary CD8
1.7
Astrocytes TNF alpha +
0.0


lymphocyte rest

IL-1beta


Secondary CD8
0.0
KU-812 (Basophil) rest
0.0


lymphocyte act


CD4 lymphocyte none
0.0
KU-812 (Basophil)
3.1




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
0.0
CCD1106
0.0


CD95 CH11

(Keratinocytes) none


LAK cells rest
0.0
CCD1106
0.5




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
0.0
Liver cirrhosis
100.0


LAK cells IL-2 + IL-12
3.6
Lupus kidney
0.0


LAK cells IL-2 + IFN
3.9
NCI-H292 none
0.0


gamma


LAK cells IL-2 + IL-18
2.4
NCI-H292 IL-4
0.0


LAK cells
0.0
NCI-H292 IL-9
0.0


PMA/ionomycin


NK Cells IL-2 rest
0.0
NCI-H292 IL-13
0.0


Two Way MLR 3 day
0.0
NCI-H292 IFN gamma
0.0


Two Way MLR 5 day
0.0
HPAEC none
0.0


Two Way MLR 7 day
0.0
HPAEC TNF alpha + IL-
0.0




1beta


PBMC rest
0.0
Lung fibroblast none
0.0


PBMC PWM
0.0
Lung fibroblast TNF
6.2




alpha + IL-1beta


PBMC PHA-L
0.0
Lung fibroblast IL-4
0.0


Ramos (B cell) none
0.0
Lung fibroblast IL-9
0.0


Ramos (B cell)
0.0
Lung fibroblast IL-13
0.3


ionomycin


B lymphocytes PWM
8.4
Lung fibroblast IFN
0.0




gamma


B lymphocytes CD40L
0.0
Dermal fibroblast
0.0


and IL-4

CCD1070 rest


EOL-1 dbcAMP
0.0
Dermal fibroblast
1.6




CCD1070 TNF alpha


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
0.0
Dermal fibroblast IFN
0.0




gamma


Dendritic cells LPS
1.5
Dermal fibroblast IL-4
0.0


Dendritic cells anti-
0.0
IBD Colitis 2
11.9


CD40


Monocytes rest
0.0
IBD Crohn's
0.0


Monocytes LPS
5.8
Colon
1.5


Macrophages rest
3.4
Lung
0.0


Macrophages LPS
0.0
Thymus
3.8


HUVEC none
0.0
Kidney
6.7


HUVEC starved
0.0










[1765] CNS_neurodegeneration_v1.0 Summary: Ag3474 Expression of the CG59568-01 gene is low/undetectable (CT values>35) across the samples in this panel. (Data not shown.)


[1766] General_screening_panel_v1.4 Summary: Ag3474 Expression of the CG59568-01 gene is low/undetectable (CT values>35) across the samples in this panel. (Data not shown.) This gene encodes a G protein-coupled receptor (GPCR), a type of cell surface receptor involved in signal transduction. It is most similar to members of the odorant receptor subfamily of GPCRs. Based on analogy to other odorant receptor genes, we predict that expression of this gene may be highest in nasal epithelium, a sample not represented on this panel.


[1767] Panel 4D Summary: Ag3474 Highest expression of the CG59280-01 gene is seen in the liver cirrhosis sample (CT=31.37). Thus, expression of this gene could be used to differentiate between this sample from the other samples on this panel and as a marker to detect the presence of liver cirrhosis. Furthermore, expression of this gene is not detected in normal liver in Panel 1.4, suggesting that its expression is unique to liver cirrhosis. This gene encodes a putative GPCR; therefore, antibodies or small molecule therapeutics could reduce or inhibit fibrosis that occurs in liver cirrhosis. In addition, antibodies to this putative GPCR could also be used for the diagnosis of liver cirrhosis.



REFERENCES

[1768] 1. Mark M. D., Wittemann S., Herlitze S. (2000) G protein modulation of recombinant P/Q-type calcium channels by regulators of G protein signalling proteins. J. Physiol 528 Pt 1: 65-77.


[1769] BK. CG59224-01 and CG59216-01: GPCR


[1770] Expression of gene CG59224-01 and variant CG59216-01 was assessed using the primer-probe sets Ag3400 and Ag3405, described in Tables BKA and BKB. Results of the RTQ-PCR runs are shown in Table BKC.


[1771] Table BKA. Probe Name Ag3400
891TABLE BKAProbe Name Ag3400StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-tctctgacctagggctgtctct-3′22225584ProbeTET-5′-tcttccttacccatcactttgggact-3′-TAMRA26248585Reverse5′-catgaatttcatggacatcaaa-3′22281586


[1772] Table BKB. Probe Name Ag3405
892TABLE BKBProbe Name Ag3405StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-cacatctgtgctgtgcttatct-3′22746587ProbeTET-5′-agtgctgccatgctccaccagttt-3′-TAMRA24785588Reverse5′-acgtggatcataggagacacat-3′22816589


[1773]

893





TABLE BKC










General_screening_panel_v1.4













Rel. Exp. (%)
Rel. Exp. (%)

Rel. Exp. (%)
Rel. Exp. (%)



Ag3400, Run
Ag3405, Run

Ag3400, Run
Ag3405, Run


Tissue Name
216822602
216838741
Tissue Name
216822602
216838741















Adipose
0.0
0.0
Renal ca. TK-10
0.0
0.0


Melanoma*
0.0
0.0
Bladder
1.2
0.0


Hs688(A).T


Melanoma*
0.0
0.0
Gastric ca. (liver
0.0
0.0


Hs688(B).T


met.) NCI-N87


Melanoma*
0.0
0.0
Gastric ca.
0.0
0.0


M14


KATO III


Melanoma*
0.0
0.0
Colon ca. SW-
0.0
0.0


LOXIMVI


948


Melanoma*
0.0
0.0
Colon ca.
0.0
0.0


SK-MEL-5


SW480


Squamous
0.0
0.0
Colon ca.*
0.0
0.0


cell


(SW480 met)


carcinoma


SW620


SCC-4


Testis Pool
0.0
0.0
Colon ca. HT29
0.0
0.0


Prostate ca.*
0.0
0.0
Colon ca. HCT-
0.0
0.0


(bone met)


116


PC-3


Prostate Pool
3.2
1.8
Colon ca. CaCo-2
0.0
0.0


Placenta
0.0
0.0
Colon cancer
0.0
0.0





tissue


Uterus Pool
0.0
0.0
Colon ca.
0.0
0.0





SW1116


Ovarian ca.
0.0
0.0
Colon ca. Colo-
0.0
0.0


OVCAR-3


205


Ovarian ca.
1.0
0.0
Colon ca. SW-48
0.0
0.0


SK-OV-3


Ovarian ca.
0.0
0.0
Colon Pool
0.0
0.0


OVCAR-4


Ovarian ca.
0.0
0.0
Small Intestine
0.0
0.0


OVCAR-5


Pool


Ovarian ca.
0.0
0.0
Stomach Pool
0.0
0.0


IGROV-1


Ovarian ca.
0.0
0.0
Bone Marrow
0.0
0.0


OVCAR-8


Pool


Ovary
0.0
0.0
Fetal Heart
0.0
0.0


Breast ca.
0.0
0.0
Heart Pool
1.7
1.3


MCF-7


Breast ca.
0.0
0.0
Lymph Node
0.0
0.0


MDA-MB-


Pool


231


Breast ca. BT
0.0
0.0
Fetal Skeletal
0.0
0.0


549


Muscle


Breast ca.
0.0
0.0
Skeletal Muscle
0.0
0.0


T47D


Pool


Breast ca.
0.0
0.5
Spleen Pool
0.0
0.0


MDA-N


Breast Pool
0.0
0.5
Thymus Pool
0.0
0.5


Trachea
0.0
0.0
CNS cancer
0.0
0.0





(glio/astro) U87-





MG


Lung
0.0
0.0
CNS cancer
0.0
0.0





(glio/astro) U-





118-MG


Fetal Lung
0.0
0.0
CNS cancer
0.0
0.0





(neuro; met) SK-





N-AS


Lung ca.
0.0
0.0
CNS cancer
0.0
0.0


NCI-N417


(astro) SF-539


Lung ca. LX-1
0.0
0.0
CNS cancer
0.0
0.0





(astro) SNB-75


Lung ca.
2.5
3.3
CNS cancer
0.0
0.0


NCI-H146


(glio) SNB-19


Lung ca.
100.0
100.0
CNS cancer
0.0
0.0


SHP-77


(glio) SF-295


Lung ca.
0.0
0.0
Brain
0.0
0.0


A549


(Amygdala) Pool


Lung ca.
0.0
0.0
Brain
0.0
0.0


NCI-H526


(cerebellum)


Lung ca.
0.0
0.0
Brain (fetal)
0.0
0.0


NCI-H23


Lung ca.
0.0
0.0
Brain
0.0
0.0


NCI-H460


(Hippocampus)





Pool


Lung ca.
0.0
0.0
Cerebral Cortex
0.0
0.6


HOP-62


Lung ca.
0.0
0.0
Brain (Substantia
0.0
0.0


NCI-H522


nigra) Pool


Liver
0.0
0.0
Brain
0.0
0.0





(Thalamus) Pool


Fetal Liver
0.0
0.0
Brain (whole)
0.0
0.0


Liver ca.
0.0
0.0
Spinal Cord Pool
0.0
0.0


HepG2


Kidney Pool
0.0
0.4
Adrenal Gland
0.0
0.0


Fetal Kidney
10.8
2.6
Pituitary gland
0.0
0.0





Pool


Renal ca.
0.0
0.0
Salivary Gland
0.0
0.0


786-0


Renal ca.
0.0
0.0
Thyroid (female)
0.0
0.0


A498


Renal ca.
0.0
0.0
Pancreatic ca.
0.0
0.0


ACHN


CAPAN2


Renal ca.
0.0
0.0
Pancreas Pool
0.0
1.2


UO-31










[1774] CNS_neurodegeneration_v1.0 Summary: Ag3400/Ag3405 Expression of the CG59224-01 gene is low/undetectable (CT values>35) across the samples in this panel. (Data not shown.)


[1775] General_screening_panel_v1.4 Summary: Ag3400/Ag3405 Two experiments with two different probe and primer sets produce results that are in excellent agreement, with significant expression of the CG59224-01 gene exclusively in a lung cancer cell line sample (CTs=30-33). Therefore, expression of this gene may be used to distinguish this sample from other samples on this panel and as a marker for lung cancer. Furthermore, therapeutic modulation of the activity of the GPCR encoded by this gene may be beneficial in the treatment of lung cancer.


[1776] Panel 4D Summary: Ag3400/Ag3405 Expression of the CG59224-01 gene is low/undetectable (CT values>35) across the samples in this panel. (Data not shown.) This gene encodes a G protein-coupled receptor (GPCR), a type of cell surface receptor involved in signal transduction. It is most similar to members of the odorant receptor subfamily of GPCRs. Based on analogy to other odorant receptor genes, we predict that expression of this gene may be highest in nasal epithelium, a sample not represented on this panel.


[1777] BL. CG59214-01 and CG59214-01: GPCR


[1778] Expression of gene CG59214-01 and CG59214-01 was assessed using the primer-probe sets Ag3398 and Ag3404, described in Tables BLA and BLB. Results of the RTQ-PCR runs are shown in Tables BLC and BLD.


[1779] Table BLA. Probe Name Ag3398
894TABLE BLAProbe Name Ag3398StartSEQPrimersSequencesLengthPositionID NO:Forward5′-atacttgcatctcccacatctg-3′22724590ProbeTET-5′-caccaatgattgggctatctatgatcca-3′-TAMRA28766591Reverse5′-tgaggaagcattctgtccatag-3′22797592


[1780] Table BLB. Probe Name Ag3404
895TABLE BLBProbe Name Ag3404StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-atacttgcatctcccacatctg-3′22724593ProbeTET-5′-caccaatgattgggctatctatgatcca-3′-TAMRA28766594Reverse5′-tgaggaagcattctgtccatag-3′22797595


[1781]

896





TABLE BLC










General_screening_panel_v1.4













Rel. Exp. (%)
Rel. Exp. (%)

Rel. Exp. (%)
Rel. Exp. (%)



Ag3398, Run
Ag3404, Run

Ag3398, Run
Ag3404, Run


Tissue Name
216822567
216838380
Tissue Name
216822567
216838380















Adipose
0.0
0.0
Renal ca. TK-10
0.0
0.0


Melanoma*
0.0
0.0
Bladder
0.0
0.0


Hs688(A).T


Melanoma*
0.0
0.0
Gastric ca. (liver
0.0
0.0


Hs688(B).T


met.) NCI-N87


Melanoma*
0.0
0.0
Gastric ca.
0.0
0.0


M14


KATO III


Melanoma*
0.0
0.0
Colon ca. SW-
0.0
0.0


LOXIMVI


948


Melanoma*
0.0
88.9
Colon ca.
0.0
0.0


SK-MEL-5


SW480


Squamous
0.0
0.0
Colon ca.*
0.0
0.0


cell


(SW480 met)


carcinoma


SW620


SCC-4


Testis Pool
0.0
0.0
Colon ca. HT29
0.0
0.0


Prostate ca.*
0.0
0.0
Colon ca. HCT-
0.0
0.0


(bone met)


116


PC-3


Prostate Pool
0.0
0.0
Colon ca. CaCo-2
0.0
0.0


Placenta
0.0
0.0
Colon cancer
0.0
0.0





tissue


Uterus Pool
0.0
0.0
Colon ca.
0.0
0.0





SW1116


Ovarian ca.
0.0
0.0
Colon ca. Colo-
0.0
0.0


OVCAR-3


205


Ovarian ca.
0.0
0.0
Colon ca. SW-48
0.0
0.0


SK-OV-3


Ovarian ca.
0.0
0.0
Colon Pool
0.0
0.0


OVCAR-4


Ovarian ca.
0.0
0.0
Small Intestine
0.0
8.9


OVCAR-5


Pool


Ovarian ca.
0.0
0.0
Stomach Pool
0.0
15.6


IGROV-1


Ovarian ca.
0.0
0.0
Bone Marrow
0.0
0.0


OVCAR-8


Pool


Ovary
0.0
7.5
Fetal Heart
0.0
0.0


Breast ca.
0.0
0.0
Heart Pool
0.0
0.0


MCF-7


Breast ca.
0.0
0.0
Lymph Node
0.0
0.0


MDA-MB-


Pool


231


Breast ca. BT
0.0
0.0
Fetal Skeletal
0.0
0.0


549


Muscle


Breast ca.
0.0
0.0
Skeletal Muscle
0.0
0.0


T47D


Pool


Breast ca.
6.9
0.0
Spleen Pool
0.0
0.0


MDA-N


Breast Pool
0.0
0.0
Thymus Pool
0.0
0.0


Trachea
0.0
0.0
CNS cancer
0.0
0.0





(glio/astro) U87-





MG


Lung
0.0
0.0
CNS cancer
0.0
12.5





(glio/astro) U-





118-MG


Fetal Lung
0.0
0.0
CNS cancer
0.0
0.0





(neuro; met) SK-





N-AS


Lung ca.
0.0
0.0
CNS cancer
0.0
0.0


NCI-N417


(astro) SF-539


Lung ca. LX-1
0.0
0.0
CNS cancer
0.0
0.0





(astro) SNB-75


Lung ca.
0.0
0.0
CNS cancer
0.0
0.0


NCI-H146


(glio) SNB-19


Lung ca.
100.0
100.0
CNS cancer
0.0
0.0


SHP-77


(glio) SF-295


Lung ca.
0.0
0.0
Brain
0.0
0.0


A549


(Amygdala) Pool


Lung ca.
0.0
0.0
Brain
0.0
0.0


NCI-H526


(cerebellum)


Lung ca.
0.0
0.0
Brain (fetal)
0.0
0.0


NCI-H23


Lung ca.
0.0
0.0
Brain
0.0
0.0


NCI-H460


(Hippocampus)





Pool


Lung ca.
0.0
0.0
Cerebral Cortex
0.0
0.0


HOP-62


Pool


Lung ca.
0.0
0.0
Brain (Substantia
0.0
0.0


NCI-H522


nigra) Pool


Liver
0.0
0.0
Brain
4.3
0.0





(Thalamus) Pool


Fetal Liver
0.0
0.0
Brain (whole)
0.0
0.0


Liver ca.
0.0
0.0
Spinal Cord Pool
0.0
0.0


HepG2


Kidney Pool
0.0
0.0
Adrenal Gland
0.0
0.0


Fetal Kidney
11.1
8.5
Pituitary gland
0.0
0.0





Pool


Renal ca.
0.0
0.0
Salivary Gland
0.0
0.0


786-0


Renal ca.
0.0
0.0
Thyroid (female)
0.0
0.0


A498


Renal ca.
0.0
0.0
Pancreatic ca.
0.0
0.0


ACHN


CAPAN2


Renal ca.
0.0
0.0
Pancreas Pool
0.0
0.0


UO-31










[1782]

897





TABLE BLD










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3404, Run

Ag3404, Run


Tissue Name
165825947
Tissue Name
165825947













Secondary Th1 act
0.0
HUVEC IL-1beta
0.0


Secondary Th2 act
0.0
HUVEC IFN gamma
0.0


Secondary Tr1 act
0.0
HUVEC TNF alpha +
0.0




IFN gamma


Secondary Th1 rest
0.0
HUVEC TNF alpha +
0.0




IL4


Secondary Th2 rest
0.0
HUVEC IL-11
0.0


Secondary Tr1 rest
0.0
Lung Microvascular EC
0.0




none


Primary Th1 act
0.0
Lung Microvascular EC
0.0




TNF alpha + IL-1beta


Primary Th2 act
0.0
Microvascular Dermal
0.0




EC none


Primary Tr1 act
0.0
Microsvasular Dermal
0.0




EC TNF alpha + IL-1beta


Primary Th1 rest
0.0
Bronchial epithelium
0.0




TNF alpha + IL1beta


Primary Th2 rest
0.0
Small airway epithelium
0.0




none


Primary Tr1 rest
0.0
Small airway epithelium
0.0




TNF alpha + IL-1beta


CD45RA CD4
0.0
Coronery artery SMC rest
0.0


lymphocyte act


CD45RO CD4
0.0
Coronery artery SMC
0.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
0.0
Astrocytes rest
0.0


Secondary CD8
0.0
Astrocytes TNF alpha +
0.0


lymphocyte rest

IL-1beta


Secondary CD8
0.0
KU-812 (Basophil) rest
0.0


lymphocyte act


CD4 lymphocyte none
0.0
KU-812 (Basophil)
5.8




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
8.9
CCD1106
0.0


CD95 CH11

(Keratinocytes) none


LAK cells rest
0.0
CCD1106
0.0




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
0.0
Liver cirrhosis
100.0


LAK cells IL-2 + IL-12
0.0
Lupus kidney
0.0


LAK cells IL-2 + IFN
0.0
NCI-H292 none
0.0


gamma


LAK cells IL-2 + IL-18
0.0
NCI-H292 IL-4
0.0


LAK cells
0.0
NCI-H292 IL-9
0.0


PMA/ionomycin


NK Cells IL-2 rest
0.0
NCI-H292 IL-13
0.0


Two Way MLR 3 day
0.0
NCI-H292 IFN gamma
0.0


Two Way MLR 5 day
0.0
HPAEC none
0.0


Two Way MLR 7 day
0.0
HPAEC TNF alpha + IL-
0.0




1beta


PBMC rest
0.0
Lung fibroblast none
0.0


PBMC PWM
0.0
Lung fibroblast TNF
0.0




alpha + IL-1beta


PBMC PHA-L
0.0
Lung fibroblast IL-4
0.0


Ramos (B cell) none
0.0
Lung fibroblast IL-9
0.0


Ramos (B cell)
0.0
Lung fibroblast IL-13
0.0


ionomycin


B lymphocytes PWM
0.0
Lung fibroblast IFN
0.0




gamma


B lymphocytes CD40L
0.0
Dermal fibroblast
0.0


and IL-4

CCD1070 rest


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0




CCD1070 TNF alpha


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
0.0
Dermal fibroblast IFN
0.0




gamma


Dendritic cells LPS
0.0
Dermal fibroblast IL-4
3.9


Dendritic cells anti-
0.0
IBD Colitis 2
7.2


CD40


Monocytes rest
0.0
IBD Crohn's
4.0


Monocytes LPS
0.0
Colon
5.5


Macrophages rest
0.0
Lung
3.1


Macrophages LPS
0.0
Thymus
0.0


HUVEC none
0.0
Kidney
0.0


HUVEC starved
0.0










[1783] CNS_neurodegeneration_v1.0 Summary: Ag3398/Ag3404 Expression of the CG59222-01 gene is low/undetectable (CT values>35) across the samples in this panel. (Data not shown.)


[1784] General_screening_panel_v1.4 Summary: Ag3398/Ag3404 Two experiments with two different probe and primer sets produce results that are in excellent agreement, with significant expression of the CG59222-01 gene exclusively in a lung cancer cell line sample (CT=33.8). Therefore, expression of this gene may be used to this sample from other samples on this panel and as a marker for lung cancer. Furthermore, therapeutic modulation of the activity of the GPCR encoded by this gene may be beneficial in the treatment of lung cancer.


[1785] Panel 4D Summary: Ag3404 Highest expression of the CG59222-01 gene is seen in the liver cirrhosis sample (CT=32.65). Thus, expression of this gene could be used to differentiate between this sample from the other samples on this panel and as a marker to detect the presence of liver cirrhosis. Furthermore, expression of this gene is not detected in normal liver in Panel 1.4, suggesting that its expression is unique to liver cirrhosis. This gene encodes a putative GPCR; therefore, antibodies or small molecule therapeutics could reduce or inhibit fibrosis that occurs in liver cirrhosis. In addition, antibodies to this putative GPCR could also be used for the diagnosis of liver cirrhosis. Ag3398 Expression of CG59222-01 gene is low/undetectable (CTs>35) across all of the samples on this panel (Data not shown).


[1786] BM. CG159220-01: GPCR


[1787] Expression of gene CG59220-01 was assessed using the primer-probe set Ag3402, described in Table BMA. Results of the RTQ-PCR runs are shown in Tables BMB, BMC and BMD.


[1788] Table BMA. Probe Name Ag3402
898TABLE BMAProbe Name Ag3402StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-ctccacacacccatgtacttct-3′22160596ProbeTET-5′-cttggatctctgccattcctctgtca-3′-TAMRA26201597Reverse5′-aggaggttctccaacagcttag-3′22233598


[1789]

899





TABLE BMB










CNS_neurodegeneration_v1.0











Rel.

Rel.



Exp. (%)

Exp. (%)



Ag3402,

Ag3402,



Run

Run


Tissue Name
210349784
Tissue Name
210349784













AD 1 Hippo
9.0
Control (Path) 3
18.6




Temporal Ctx


AD 2 Hippo
46.3
Control (Path) 4
56.6




Temporal Ctx


AD 3 Hippo
8.8
AD 1 Occipital Ctx
21.6


AD 4 Hippo
24.1
AD 2 Occipital Ctx
0.0




(Missing)


AD 5 Hippo
52.9
AD 3 Occipital Ctx
15.0


AD 6 Hippo
39.2
AD 4 Occipital Ctx
48.0


Control 2 Hippo
41.8
AD 5 Occipital Ctx
56.3


Control 4 Hippo
18.2
AD 6 Occipital Ctx
31.4


Control (Path) 3
13.7
Control 1 Occipital
14.4


Hippo

Ctx


AD 1 Temporal
27.4
Control 2 Occipital
55.5


Ctx

Ctx


AD 2 Temporal
57.0
Control 3 Occipital
42.3


Ctx

Ctx


AD 3 Temporal
10.2
Control 4 Occipital
21.2


Ctx

Ctx


AD 4 Temporal
54.3
Control (Path) 1
100.0


Ctx

Occipital Ctx


AD 5 Inf Temporal
42.9
Control (Path) 2
27.7


Ctx

Occipital Ctx


AD 5 Sup
28.7
Control (Path) 3
9.0


Temporal Ctx

Occipital Ctx


AD 6 Inf Temporal
41.8
Control (Path) 4
34.2


Ctx

Occipital Ctx


AD 6 Sup
51.4
Control 1 Parietal
23.5


Temporal Ctx

Ctx


Control 1
18.2
Control 2 Parietal
28.5


Temporal Ctx

Ctx


Control 2
43.2
Control 3 Parietal
29.5


Temporal Ctx

Ctx


Control 3
32.8
Control (Path) 1
99.3


Temporal Ctx

Parietal Ctx


Control 3
20.0
Control (Path) 2
46.7


Temporal Ctx

Parietal Ctx


Control (Path) 1
87.1
Control (Path) 3
12.0


Temporal Ctx

Parietal Ctx


Control (Path) 2
60.3
Control (Path) 4
82.4


Temporal Ctx

Parietal Ctx










[1790]

900





TABLE BMC










General_screening_panel_v1.4











Rel.

Rel.



Exp. (%)

Exp. (%)



Ag3402,

Ag3402,



Run

Run


Tissue Name
216823314
Tissue Name
216823314













Adipose
14.7
Renal ca. TK-10
2.5


Melanoma*
10.1
Bladder
28.7


Hs688(A).T


Melanoma*
1.4
Gastric ca. (liver met.)
17.9


Hs688(B).T

NCI-N87


Melanoma* M14
0.9
Gastric ca. KATO III
0.7


Melanoma*
0.8
Colon ca. SW-948
0.0


LOXIMVI


Melanoma* SK-
2.1
Colon ca. SW480
1.7


MEL-5


Squamous cell
2.9
Colon ca.* (SW480
1.8


carcinoma SCC-4

met) SW620


Testis Pool
25.9
Colon ca. HT29
1.3


Prostate ca.* (bone
1.2
Colon ca. HCT-116
0.0


met) PC-3


Prostate Pool
16.0
Colon ca. CaCo-2
0.7


Placenta
1.3
Colon cancer tissue
7.4


Uterus Pool
15.6
Colon ca. SW1116
0.0


Ovarian ca.
3.1
Colon ca. Colo-205
0.0


OVCAR-3


Ovarian ca. SK-
6.0
Colon ca. SW-48
0.0


OV-3


Ovarian ca.
0.6
Colon Pool
49.7


OVCAR-4


Ovarian ca.
2.9
Small Intestine Pool
53.6


OVCAR-5


Ovarian ca.
1.6
Stomach Pool
15.8


IGROV-1


Ovarian ca.
1.6
Bone Marrow Pool
14.5


OVCAR-8


Ovary
48.3
Fetal Heart
9.1


Breast ca. MCF-7
0.6
Heart Pool
39.5


Breast ca. MDA-
0.0
Lymph Node Pool
39.2


MB-231


Breast ca. BT 549
2.4
Fetal Skeletal Muscle
5.8


Breast ca. T47D
1.3
Skeletal Muscle Pool
47.6


Breast ca. MDA-N
0.4
Spleen Pool
22.2


Breast Pool
31.6
Thymus Pool
12.9


Trachea
5.9
CNS cancer
0.8




(glio/astro) U87-MG


Lung
16.6
CNS cancer
3.4




(glio/astro) U-118-MG


Fetal Lung
30.8
CNS cancer
1.5




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.0
CNS cancer (astro)
0.0




SF-539


Lung ca. LX-1
9.7
CNS cancer (astro)
1.1




SNB-75


Lung ca. NCI-H146
0.0
CNS cancer (glio)
1.1




SNB-19


Lung ca. SHP-77
0.6
CNS cancer (glio) SF-
4.1




295


Lung ca. A549
0.6
Brain (Amygdala)
28.1




Pool


Lung ca. NCI-H526
0.0
Brain (cerebellum)
35.1


Lung ca. NCI-H23
5.9
Brain (fetal)
12.3


Lung ca. NCI-H460
0.9
Brain (Hippocampus)
39.8




Pool


Lung ca. HOP-62
1.6
Cerebral Cortex Pool
88.9


Lung ca. NCI-H522
7.1
Brain (Substantia
43.2




nigra) Pool


Liver
0.0
Brain (Thalamus) Pool
74.2


Fetal Liver
2.5
Brain (whole)
26.1


Liver ca. HepG2
0.7
Spinal Cord Pool
100.0


Kidney Pool
51.8
Adrenal Gland
24.1


Fetal Kidney
16.7
Pituitary gland Pool
8.6


Renal ca. 786-0
0.8
Salivary Gland
3.2


Renal ca. A498
0.0
Thyroid (female)
8.9


Renal ca. ACHN
1.4
Pancreatic ca.
0.8




CAPAN2


Renal ca. UO-31
1.5
Pancreas Pool
24.8










[1791]

901





TABLE BMD










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3402, Run

Ag3402, Run


Tissue Name
165825209
Tissue Name
165825209













Secondary Th1 act
0.0
HUVEC IL-1beta
3.5


Secondary Th2 act
0.0
HUVEC IFN gamma
6.5


Secondary Tr1 act
3.3
HUVEC TNF alpha +
15.4




IFN gamma


Secondary Th1 rest
0.0
HUVEC TNF alpha +
2.9




IL4


Secondary Th2 rest
5.2
HUVEC IL-11
9.0


Secondary Tr1 rest
0.0
Lung Microvascular EC
2.7




none


Primary Th1 act
5.4
Lung Microvascular EC
0.0




TNF alpha + IL-1beta


Primary Th2 act
0.0
Microvascular Dermal
3.0




EC none


Primary Tr1 act
0.0
Microsvasular Dermal
10.7




EC TNF alpha + IL-1beta


Primary Th1 rest
3.3
Bronchial epithelium
18.0




TNF alpha + IL1beta


Primary Th2 rest
5.1
Small airway epithelium
0.0




none


Primary Tr1 rest
0.0
Small airway epithelium
79.0




TNF alpha + IL-1beta


CD45RA CD4
2.7
Coronery artery SMC rest
0.0


lymphocyte act


CD45RO CD4
0.0
Coronery artery SMC
2.5


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
0.0
Astrocytes rest
11.3


Secondary CD8
3.0
Astrocytes TNF alpha +
75.3


lymphocyte rest

IL-1beta


Secondary CD8
0.0
KU-812 (Basophil) rest
2.6


lymphocyte act


CD4 lymphocyte none
0.0
KU-812 (Basophil)
6.8




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
1.6
CCD1106
0.0


CD95 CH11

(Keratinocytes) none


LAK cells rest
0.0
CCD1106
27.9




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
5.1
Liver cirrhosis
90.8


LAK cells IL-2 + IL-12
3.0
Lupus kidney
51.8


LAK cells IL-2 + IFN
4.5
NCI-H292 none
28.1


gamma


LAK cells IL-2 + IL-18
23.2
NCI-H292 IL-4
10.6


LAK cells
0.0
NCI-H292 IL-9
23.5


PMA/ionomycin


NK Cells IL-2 rest
6.2
NCI-H292 IL-13
4.8


Two Way MLR 3 day
12.1
NCI-H292 IFN gamma
10.3


Two Way MLR 5 day
3.1
HPAEC none
5.8


Two Way MLR 7 day
5.8
HPAEC TNF alpha + IL-
0.0




1beta


PBMC rest
0.0
Lung fibroblast none
3.7


PBMC PWM
0.0
Lung fibroblast TNF
0.0




alpha + IL-1beta


PBMC PHA-L
0.0
Lung fibroblast IL-4
0.0


Ramos (B cell) none
0.0
Lung fibroblast IL-9
6.4


Ramos (B cell)
0.0
Lung fibroblast IL-13
3.2


ionomycin


B lymphocytes PWM
2.6
Lung fibroblast IFN
10.5




gamma


B lymphocytes CD40L
1.8
Dermal fibroblast
0.0


and IL-4

CCD1070 rest


EOL-1 dbcAMP
0.0
Dermal fibroblast
13.7




CCD1070 TNF alpha


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
6.5
Dermal fibroblast IFN
0.0




gamma


Dendritic cells LPS
4.7
Dermal fibroblast IL-4
6.3


Dendritic cells anti-
0.0
IBD Colitis 2
27.0


CD40


Monocytes rest
24.8
IBD Crohn's
9.3


Monocytes LPS
3.1
Colon
100.0


Macrophages rest
4.0
Lung
24.7


Macrophages LPS
0.0
Thymus
59.5


HUVEC none
6.5
Kidney
27.0


HUVEC starved
41.2










[1792] CNS_neurodegeneration_v1.0 Summary: Ag3402 The CG59220-01 gene is expressed at low levels throughout the CNS, including in amygdala, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. The GPCR family of receptors contains a large number of neurotransmitter receptors, including the dopamine, serotonin, a and b-adrenerlyic, acetylcholine muscarinic, histamine, peptide, and metabotropic glutamate receptors. GPCRs are excellent drug targets in various neurologic and psychiatric diseases. All antipsychotics have been shown to act at the dopamine D2 receptor; similarly novel antipsychotics also act at the serotonergic receptor, and often the muscarinic and adrenergic receptors as well. While the majority of antidepressants can be classified as selective serotonin reuptake inhibitors, blockade of the 5-HT1A and a2 adrenergic receptors increases the effects of these drugs. The GPCRs are also of use as drug targets in the treatment of stroke. Blockade of the glutamate receptors may decrease the neuronal death resulting from excitotoxicity; further more the purinergic receptors have also been implicated as drug targets in the treatment of cerebral ischemia. The b-adrenergic receptors have been implicated in the treatment of ADHD with Ritalin, while the a-adrenergic receptors have been implicated in memory. Therefore this gene may be of use as a small molecule target for the treatment of any of the described diseases.


[1793] General_screening_panel_v1.4 Summary: Ag3402 The CG59220-01 gene represents a novel G-protein coupled receptor (GPCR) with highest expression in spinal cord sample (CT=31.12) and moderate expression in other samples from brain. Please see Panel CNS_neurodegeneration_v1.0 for discussion of utility of this gene in the central nervous system.


[1794] Low levels of expression of the CG59220-01 gene are also observed in areas outside of the central nervous system such as the, adipose tissue, fetal and adult heart, skeletal muscle, adrenal gland, pituitary gland, and thyroid suggesting the possibility of a wider role in intercellular signaling. Therapeutic modulation of the expression or function of this gene may therefore be useful in the treatment of metabolic disorders, including obesity and diabetes.


[1795] Panel 4D Summary: Ag3402 The CG59220-01 gene represents a novel G-protein coupled receptor (GPCR) with highest expression in colon (CT=33.12). Thus expression of this gene can be used to distinguish these samples from other samples used in this panel. In addition, expression of this gene is low/undetectable (CT values>35) in samples derived from IBD colitis and IBS Crohn's. Therefore, expression of this gene can be used to distinguish normal colon sample from the IBD colitis and IBD Crohn's sample used in this panel.


[1796] BN. CG59218-01: GPCR


[1797] Expression of gene CG59218-01 was assessed using the primer-probe set Ag3401, described in Table BNA. Results of the RTQ-PCR runs are shown in Tables BNB.


[1798] Table BNA. Probe Name Ag3401
902TABLE BNAProbe Name Ag3401StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-gctggctactaggtttctcctt-3′22447599ProbeTET-5′-atcatcatgcctgtcatcctgaccag-3′-TAMRA26470600Reverse5′-ttgatgtgggtatcacagaatg-3′22504601


[1799]

903





TABLE BNB










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3401, Run

Ag3401, Run


Tissue Name
165825154
Tissue Name
165825154













Secondary Th1 act
2.4
HUVEC IL-1beta
0.0


Secondary Th2 act
3.4
HUVEC IFN gamma
0.0


Secondary Tr1 act
8.4
HUVEC TNF alpha +
0.0




IFN gamma


Secondary Th1 rest
3.1
HUVEC TNF alpha +
0.0




IL4


Secondary Th2 rest
0.0
HUVEC IL-11
0.0


Secondary Tr1 rest
0.0
Lung Microvascular EC
0.0




none


Primary Th1 act
0.0
Lung Microvascular EC
0.0




TNF alpha + IL-1beta


Primary Th2 act
3.1
Microvascular Dermal
0.0




EC none


Primary Tr1 act
0.0
Microsvasular Dermal
0.0




EC TNF alpha + IL-1beta


Primary Th1 rest
8.1
Bronchial epithelium
0.0




TNF alpha + IL1beta


Primary Th2 rest
0.0
Small airway epithelium
0.0




none


Primary Tr1 rest
3.3
Small airway epithelium
0.0




TNF alpha + IL-1beta


CD45RA CD4
0.0
Coronery artery SMC rest
0.0


lymphocyte act


CD45RO CD4
0.0
Coronery artery SMC
0.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
8.1
Astrocytes rest
5.7


Secondary CD8
0.0
Astrocytes TNF alpha +
0.0


lymphocyte rest

IL-1beta


Secondary CD8
1.0
KU-812 (Basophil) rest
0.0


lymphocyte act


CD4 lymphocyte none
0.0
KU-812 (Basophil)
0.0




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
5.7
CCD1106
0.0


CD95 CH11

(Keratinocytes) none


LAK cells rest
0.0
CCD1106
0.0




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
3.1
Liver cirrhosis
100.0


LAK cells IL-2 + IL-12
3.2
Lupus kidney
0.0


LAK cells IL-2 + IFN
8.0
NCI-H292 none
0.0


gamma


LAK cells IL-2 + IL-18
4.3
NCI-H292 IL-4
0.0


LAK cells
2.1
NCI-H292 IL-9
0.0


PMA/ionomycin


NK Cells IL-2 rest
0.0
NCI-H292 IL-13
0.0


Two Way MLR 3 day
0.0
NCI-H292 IFN gamma
0.0


Two Way MLR 5 day
0.0
HPAEC none
0.0


Two Way MLR 7 day
0.0
HPAEC TNF alpha + IL-
0.0




1beta


PBMC rest
0.0
Lung fibroblast none
0.0


PBMC PWM
3.3
Lung fibroblast TNF
0.0




alpha + IL-1beta


PBMC PHA-L
0.0
Lung fibroblast IL-4
0.0


Ramos (B cell) none
0.0
Lung fibroblast IL-9
0.0


Ramos (B cell)
0.0
Lung fibroblast IL-13
0.0


ionomycin


B lymphocytes PWM
3.4
Lung fibroblast IFN
0.0




gamma


B lymphocytes CD40L
0.0
Dermal fibroblast
2.5


and IL-4

CCD1070 rest


EOL-1 dbcAMP
0.0
Dermal fibroblast
14.8




CCD1070 TNF alpha


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
6.0
Dermal fibroblast IFN
0.0




gamma


Dendritic cells LPS
0.0
Dermal fibroblast IL-4
0.0


Dendritic cells anti-
0.0
IBD Colitis 2
17.1


CD40


Monocytes rest
0.0
IBD Crohn's
0.0


Monocytes LPS
6.1
Colon
0.0


Macrophages rest
0.0
Lung
0.0


Macrophages LPS
0.0
Thymus
0.0


HUVEC none
0.0
Kidney
3.2


HUVEC starved
0.0










[1800] CNS_neurodegeneration_v1.0 Summary: Ag3401 Expression of the CG59218-01 gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1801] General_screening_panel_v1.4 Summary: Ag3401 Expression of the CG59218-01 gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown). This gene product is most similar to members of the odorant receptor subfamily of GPCRs. Based on analogy to other odorant receptor genes, we predict that expression of this gene may be highest in nasal epithelium, a sample not represented on this panel.


[1802] Panel 4D Summary: Ag3401 Highest expression of the CG59218-01 gene is seen in the liver cirrhosis sample (CT=33.03). Thus, expression of this gene could be used to differentiate between this sample from the other samples on this panel and as a marker to detect the presence of liver cirrhosis. Furthermore, expression of this gene is not detected in normal liver in Panel 1.4, suggesting that its expression is unique to liver cirrhosis. This gene encodes a putative GPCR; therefore, antibodies or small molecule therapeutics could reduce or inhibit fibrosis that occurs in liver cirrhosis. In addition, antibodies to this putative GPCR could also be used for the diagnosis of liver cirrhosis.


[1803] BO. CG59211-01: GPCR


[1804] Expression of gene CG59211-01 was assessed using the primer-probe set Ag3397, described in Table BOA. Results of the RTQ-PCR runs are shown in Table BOB.
904TABLE BOAProbe Name A3397StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-tcacaggcatcctagacttgac-3′22645602ProbeTET-5′-tcatgtcctacatgttgatactgaaagca-3′-TAMRA29675603Reverse5′-tttcttgatgctatgctcaaca-3′22705604


[1805]

905





TABLE BOB










General_screening_panel_v1.4











Rel.

Rel.



Exp. (%)

Exp. (%)



Ag3397,

Ag3397,



Run

Run


Tissue Name
216822307
Tissue Name
216822307













Adipose
0.0
Renal ca. TK-10
0.0


Melanoma*
0.0
Bladder
0.0


Hs688(A).T


Melanoma*
0.0
Gastric ca. (liver met.)
0.0


Hs688(B).T

NCI-N87


Melanoma* M14
0.0
Gastric ca. KATO III
0.0


Melanoma*
0.0
Colon ca. SW-948
0.0


LOXIMVI


Melanoma* SK-
0.0
Colon ca. SW480
0.0


MEL-5


Squamous cell
0.0
Colon ca.* (SW480
0.7


carcinoma SCC-4

met) SW620


Testis Pool
0.0
Colon ca. HT29
0.0


Prostate ca.* (bone
0.0
Colon ca. HCT-116
0.0


met) PC-3


Prostate Pool
0.0
Colon ca. CaCo-2
0.0


Placenta
0.0
Colon cancer tissue
0.0


Uterus Pool
0.0
Colon ca. SW1116
0.0


Ovarian ca.
0.0
Colon ca. Colo-205
0.0


OVCAR-3


Ovarian ca. SK-
0.0
Colon ca. SW-48
0.0


OV-3


Ovarian ca.
0.0
Colon Pool
0.6


OVCAR-4


Ovarian ca.
0.0
Small Intestine Pool
0.0


OVCAR-5


Ovarian ca.
0.0
Stomach Pool
0.0


IGROV-1


Ovarian ca.
0.0
Bone Marrow Pool
0.0


OVCAR-8


Ovary
0.0
Fetal Heart
0.5


Breast ca. MCF-7
0.0
Heart Pool
0.5


Breast ca. MDA-
0.0
Lymph Node Pool
0.0


MB-231


Breast ca. BT 549
0.0
Fetal Skeletal Muscle
0.0


Breast ca. T47D
0.0
Skeletal Muscle Pool
0.0


Breast ca. MDA-N
0.0
Spleen Pool
0.0


Breast Pool
0.6
Thymus Pool
0.0


Trachea
0.0
CNS cancer
0.0




(glio/astro) U87-MG


Lung
0.0
CNS cancer
0.0




(glio/astro) U-118-MG


Fetal Lung
0.0
CNS cancer
0.8




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.0
CNS cancer (astro)
0.0




SF-539


Lung ca. LX-1
0.0
CNS cancer (astro)
0.0




SNB-75


Lung ca. NCI-H146
2.6
CNS cancer (glio)
0.0




SNB-19


Lung ca. SHP-77
100.0
CNS cancer (glio) SF-
0.0




295


Lung ca. A549
0.0
Brain (Amygdala)
0.0




Pool


Lung ca. NCI-H526
0.0
Brain (cerebellum)
0.0


Lung ca. NCI-H23
0.0
Brain (fetal)
0.0


Lung ca. NCI-H460
0.0
Brain (Hippocampus)
0.0




Pool


Lung ca. HOP-62
0.0
Cerebral Cortex Pool
0.0


Lung ca. NCI-H522
0.0
Brain (Substantia
0.0




nigra) Pool


Liver
0.0
Brain (Thalamus) Pool
0.0


Fetal Liver
0.0
Brain (whole)
0.9


Liver ca. HepG2
0.0
Spinal Cord Pool
0.0


Kidney Pool
0.9
Adrenal Gland
0.0


Fetal Kidney
3.3
Pituitary gland Pool
0.0


Renal ca. 786-0
0.0
Salivary Gland
0.0


Renal ca. A498
0.0
Thyroid (female)
0.0


Renal ca. ACHN
0.0
Pancreatic ca.
0.0




CAPAN2


Renal ca. UO-31
0.0
Pancreas Pool
0.0










[1806] CNS_neurodegeneration_v1.0 Summary: Ag3397 Expression of the CG59211-01 gene is low/undetectable (CT values>35) across the samples in this panel. (Data not shown.) This gene encodes a G protein-coupled receptor (GPCR), a type of cell surface receptor involved in signal transduction. It is most similar to members of the odorant receptor subfamily of GPCRs. Based on analogy to other odorant receptor genes, we predict that expression of this gene may be highest in nasal epithelium, a sample not represented on this panel.


[1807] General_screening_panel_v1.4 Summary: Ag3397 Significant expression of the CG59211-01 gene is seen exclusively in one of the lung cancer sample (CT=32.29). Therefore, expression of this gene may be used to distinguish this sample from other samples on this panel and as a marker for lung cancer. There is an increasing awareness that some GPCRs can regulate proliferative signaling pathways and that chronic stimulation or mutational activation of receptors can lead to oncogenic transformation. Activating mutations in GPCRs are associated with several types of human tumors and some receptors exhibit potent oncogenic activity due to agonist overexpression (Whitehead et al., 2001). Therefore, therapeutic modulation of the activity of the GPCR encoded by this gene may be beneficial in the treatment of lung cancer.



REFERENCES

[1808] 1. Whitehead I P, Zohn I E, Der C J. (2001) Rho GTPase-dependent transformation by G protein-coupled receptors. Oncogene Mar. 26, 2001;20(13):1547-55


[1809] Panel 4D Summary: Ag3397 Expression of the CG59211-01 gene is low/undetectable (CT values>35) across the samples in this panel. (Data not shown.)


[1810] BP. CG59276-01: Dihydroorotate Dehydrogenase


[1811] Expression of gene CG59276-01 was assessed using the primer-probe set Ag3524, described in Table BPA. Results of the RTQ-PCR runs are shown in Tables BPB, BPC, BPD, BPE and BPF.
906TABLE BPAProbe Name Ag3524StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-ttcaggcactgttctttgactt-3′221439605ProbeTET-5′-aacagattttgcaacactttccaagg-3′-TAMRA261472606Reverse5′-tgagggagtggtaacactgtgt-3′221498607


[1812]

907





TABLE BPB










CNS_neurodegeneration_v1.0











Rel.

Rel.



Exp. (%)

Exp. (%)



Ag3524,

Ag3524,



Run

Run


Tissue Name
206915926
Tissue Name
206915926













AD 1 Hippo
26.8
Control (Path) 3
18.9




Temporal Ctx


AD 2 Hippo
30.8
Control (Path) 4
51.4




Temporal Ctx


AD 3 Hippo
25.3
AD 1 Occipital Ctx
37.1


AD 4 Hippo
38.2
AD 2 Occipital Ctx
0.0




(Missing)


AD 5 Hippo
77.4
AD 3 Occipital Ctx
16.5


AD 6 Hippo
83.5
AD 4 Occipital Ctx
40.9


Control 2 Hippo
43.8
AD 5 Occipital Ctx
33.9


Control 4 Hippo
20.6
AD 6 Occipital Ctx
17.0


Control (Path) 3
17.6
Control 1 Occipital
6.3


Hippo

Ctx


AD 1 Temporal
37.1
Control 2 Occipital
74.7


Ctx

Ctx


AD 2 Temporal
31.2
Control 3 Occipital
22.1


Ctx

Ctx


AD 3 Temporal
6.5
Control 4 Occipital
25.7


Ctx

Ctx


AD 4 Temporal
79.6
Control (Path) 1
89.5


Ctx

Occipital Ctx


AD 5 Inf Temporal
97.9
Control (Path) 2
18.4


Ctx

Occipital Ctx


AD 5 Sup
56.3
Control (Path) 3
11.2


Temporal Ctx

Occipital Ctx


AD 6 Inf Temporal
100.0
Control (Path) 4
24.8


Ctx

Occipital Ctx


AD 6 Sup
66.9
Control 1 Parietal
26.8


Temporal Ctx

Ctx


Control 1
10.6
Control 2 Parietal
68.3


Temporal Ctx

Ctx


Control 2
13.4
Control 3 Parietal
28.1


Temporal Ctx

Ctx


Control 3
25.9
Control (Path) 1
58.6


Temporal Ctx

Parietal Ctx


Control 3
36.6
Control (Path) 2
51.4


Temporal Ctx

Parietal Ctx


Control (Path) 1
80.7
Control (Path) 3
6.9


Temporal Ctx

Parietal Ctx


Control (Path) 2
76.8
Control (Path) 4
54.7


Temporal Ctx

Parietal Ctx










[1813]

908





TABLE BPC










General_screening_panel_v1.4











Rel.

Rel.



Exp. (%)

Exp. (%)



Ag3524,

Ag3524,



Run

Run


Tissue Name
213390931
Tissue Name
213390931













Adipose
6.2
Renal ca. TK-10
9.3


Melanoma*
3.1
Bladder
22.1


Hs688(A).T


Melanoma*
9.2
Gastric ca. (liver met.)
24.8


Hs688(B).T

NCI-N87


Melanoma* M14
0.9
Gastric ca. KATO III
0.0


Melanoma*
0.4
Colon ca. SW-948
1.2


LOXIMVI


Melanoma* SK-
0.7
Colon ca. SW480
4.2


MEL-5


Squamous cell
0.0
Colon ca.* (SW480
10.5


carcinoma SCC-4

met) SW620


Testis Pool
11.3
Colon ca. HT29
1.1


Prostate ca.* (bone
3.1
Colon ca. HCT-116
5.3


met) PC-3


Prostate Pool
8.7
Colon ca. CaCo-2
8.5


Placenta
1.3
Colon cancer tissue
7.2


Uterus Pool
2.9
Colon ca. SW1116
1.4


Ovarian ca.
6.9
Colon ca. Colo-205
1.6


OVCAR-3


Ovarian ca. SK-
11.7
Colon ca. SW-48
1.7


OV-3


Ovarian ca.
0.2
Colon Pool
12.6


OVCAR-4


Ovarian ca.
8.5
Small Intestine Pool
20.9


OVCAR-5


Ovarian ca.
2.5
Stomach Pool
13.2


IGROV-1


Ovarian ca.
4.1
Bone Marrow Pool
8.7


OVCAR-8


Ovary
15.3
Fetal Heart
9.5


Breast ca. MCF-7
3.4
Heart Pool
11.3


Breast ca. MDA-
3.1
Lymph Node Pool
27.2


MB-231


Breast ca. BT 549
23.5
Fetal Skeletal Muscle
9.1


Breast ca. T47D
19.5
Skeletal Muscle Pool
6.7


Breast ca. MDA-N
0.3
Spleen Pool
8.9


Breast Pool
25.2
Thymus Pool
18.2


Trachea
12.6
CNS cancer
8.7




(glio/astro) U87-MG


Lung
13.3
CNS cancer
7.5




(glio/astro) U-118-MG


Fetal Lung
41.8
CNS cancer
21.3




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.0
CNS cancer (astro)
2.4




SF-539


Lung ca. LX-1
32.1
CNS cancer (astro)
97.9




SNB-75


Lung ca. NCI-H146
1.4
CNS cancer (glio)
3.0




SNB-19


Lung ca. SHP-77
2.3
CNS cancer (glio) SF-
26.1




295


Lung ca. A549
5.4
Brain (Amygdala)
4.1




Pool


Lung ca. NCI-H526
0.4
Brain (cerebellum)
33.0


Lung ca. NCI-H23
100.0
Brain (fetal)
25.5


Lung ca. NCI-H460
7.9
Brain (Hippocampus)
7.5




Pool


Lung ca. HOP-62
4.2
Cerebral Cortex Pool
7.7


Lung ca. NCI-H522
1.4
Brain (Substantia
5.8




nigra) Pool


Liver
1.4
Brain (Thalamus) Pool
11.7


Fetal Liver
9.3
Brain (whole)
9.5


Liver ca. HepG2
5.2
Spinal Cord Pool
10.5


Kidney Pool
40.3
Adrenal Gland
9.1


Fetal Kidney
40.1
Pituitary gland Pool
2.0


Renal ca. 786-0
12.9
Salivary Gland
8.3


Renal ca. A498
3.4
Thyroid (female)
2.5


Renal ca. ACHN
5.4
Pancreatic ca.
9.3




CAPAN2


Renal ca. UO-31
7.2
Pancreas Pool
20.9










[1814]

909





TABLE BPD










Panel 2D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3524,

Ag3524,


Tissue Name
Run 169590472
Tissue Name
Run 169590472













Normal Colon
28.1
Kidney Margin
1.8




8120608


CC Well to Mod Diff
2.4
Kidney Cancer
2.7


(ODO3866)

8120613


CC Margin (ODO3866)
1.4
Kidney Margin
8.0




8120614


CC Gr.2 rectosigmoid
3.5
Kidney Cancer
6.0


(ODO3868)

9010320


CC Margin (ODO3868)
1.1
Kidney Margin
11.7




9010321


CC Mod Diff
9.9
Normal Uterus
4.8


(ODO3920)


CC Margin (ODO3920)
6.0
Uterus Cancer
2.3




064011


CC Gr.2 ascend colon
12.3
Normal Thyroid
6.6


(ODO3921)


CC Margin (ODO3921)
3.1
Thyroid Cancer
0.5




064010


CC from Partial
12.8
Thyroid Cancer
2.1


Hepatectomy

A302152


(ODO4309) Mets


Liver Margin
34.6
Thyroid Margin
9.2


(ODO4309)

A302153


Colon mets to lung
12.2
Normal Breast
13.6


(OD04451-01)


Lung Margin (OD04451-
2.9
Breast Cancer
6.4


02)

(OD04566)


Normal Prostate 6546-1
9.9
Breast Cancer
9.8




(OD04590-01)


Prostate Cancer
16.6
Breast Cancer Mets
14.0


(OD04410)

(OD04590-03)


Prostate Margin
15.4
Breast Cancer
5.3


(OD04410)

Metastasis




(OD04655-05)


Prostate Cancer
20.6
Breast Cancer
11.2


(OD04720-01)

064006


Prostate Margin
16.6
Breast Cancer 1024
31.6


(OD04720-02)


Normal Lung 061010
27.2
Breast Cancer
8.0




9100266


Lung Met to Muscle
3.5
Breast Margin
4.6


(ODO4286)

9100265


Muscle Margin
6.7
Breast Cancer
4.1


(ODO4286)

A209073


Lung Malignant Cancer
3.7
Breast Margin
8.4


(OD03126)

A209073


Lung Margin (OD03126)
10.8
Normal Liver
100.0


Lung Cancer (OD04404)
4.1
Liver Cancer 064003
44.4


Lung Margin (OD04404)
4.3
Liver Cancer 1025
47.0


Lung Cancer (OD04565)
0.9
Liver Cancer 1026
0.9


Lung Margin (OD04565)
8.5
Liver Cancer 6004-T
59.5


Lung Cancer (OD04237-
13.2
Liver Tissue 6004-N
6.6


01)


Lung Margin (OD04237-
4.5
Liver Cancer 6005-T
1.5


02)


Ocular Mel Met to Liver
6.7
Liver Tissue 6005-N
0.5


(ODO4310)


Liver Margin
6.7
Normal Bladder
21.5


(ODO4310)


Melanoma Mets to Lung
3.9
Bladder Cancer 1023
0.9


(OD04321)


Lung Margin (OD04321)
4.7
Bladder Cancer
5.9




A302173


Normal Kidney
35.8
Bladder Cancer
5.5




(OD04718-01)


Kidney Ca, Nuclear
18.0
Bladder Normal
6.5


grade 2 (OD04338)

Adjacent (OD04718-




03)


Kidney Margin
14.1
Normal Ovary
4.5


(OD04338)


Kidney Ca Nuclear
13.7
Ovarian Cancer
3.7


grade 1/2 (OD04339)

064008


Kidney Margin
9.9
Ovarian Cancer
11.0


(OD04339)

(OD04768-07)


Kidney Ca, Clear cell
10.8
Ovary Margin
1.1


type (OD04340)

(OD04768-08)


Kidney Margin
12.7
Normal Stomach
7.6


(OD04340)


Kidney Ca, Nuclear
0.5
Gastric Cancer
3.3


grade 3 (OD04348)

9060358


Kidney Margin
10.6
Stomach Margin
4.0


(OD04348)

9060359


Kidney Cancer
0.9
Gastric Cancer
8.2


(OD04622-01)

9060395


Kidney Margin
1.6
Stomach Margin
5.5


(OD04622-03)

9060394


Kidney Cancer
4.2
Gastric Cancer
3.8


(OD04450-01)

9060397


Kidney Margin
5.4
Stomach Margin
0.9


(OD04450-03)

9060396


Kidney Cancer 8120607
1.0
Gastric Cancer
14.5




064005










[1815]

910





TABLE BPE










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3524, Run

Ag3524, Run


Tissue Name
166445583
Tissue Name
166445583













Secondary Th1 act
13.9
HUVEC IL-1beta
2.4


Secondary Th2 act
17.1
HUVEC IFN gamma
16.4


Secondary Tr1 act
15.4
HUVEC TNF alpha +
4.8




IFN gamma


Secondary Th1 rest
36.6
HUVEC TNF alpha +
3.8




IL4


Secondary Th2 rest
19.1
HUVEC IL-11
6.1


Secondary Tr1 rest
28.7
Lung Microvascular EC
9.2




none


Primary Th1 act
10.2
Lung Microvascular EC
5.0




TNF alpha + IL-1beta


Primary Th2 act
18.2
Microvascular Dermal
14.5




EC none


Primary Tr1 act
28.5
Microsvasular Dermal
10.4




EC TNF alpha + IL-1beta


Primary Th1 rest
100.0
Bronchial epithelium
6.1




TNF alpha + IL-1beta


Primary Th2 rest
42.3
Small airway epithelium
3.3




none


Primary Tr1 rest
35.8
Small airway epithelium
29.3




TNF alpha + IL-1beta


CD45RA CD4
14.6
Coronery artery SMC rest
5.6


lymphocyte act


CD45RO CD4
28.7
Coronery artery SMC
3.4


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
17.7
Astrocytes rest
12.1


Secondary CD8
23.7
Astrocytes TNF alpha +
11.5


lymphocyte rest

IL-1beta


Secondary CD8
12.7
KU-812 (Basophil) rest
23.2


lymphocyte act


CD4 lymphocyte none
22.2
KU-812 (Basophil)
37.1




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
39.5
CCD1106
5.0


CD95 CH11

(Keratinocytes) none


LAK cells rest
17.9
CCD1106
41.5




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
41.2
Liver cirrhosis
37.9


LAK cells IL-2 + IL-12
31.0
Lupus kidney
21.8


LAK cells IL-2 + IFN
47.0
NCI-H292 none
25.0


gamma


LAK cells IL-2 + IL-18
44.8
NCI-H292 IL-4
21.3


LAK cells
5.3
NCI-H292 IL-9
21.6


PMA/ionomycin


NK Cells IL-2 rest
17.8
NCI-H292 IL-13
9.2


Two Way MLR 3 day
47.6
NCI-H292 IFN gamma
10.6


Two Way MLR 5 day
13.0
HPAEC none
16.5


Two Way MLR 7 day
18.8
HPAEC TNF alpha + IL-
4.0




1beta


PBMC rest
7.6
Lung fibroblast none
30.4


PBMC PWM
24.7
Lung fibroblast TNF
24.3




alpha + IL-1beta


PBMC PHA-L
4.9
Lung fibroblast IL-4
23.8


Ramos (B cell) none
19.5
Lung fibroblast IL-9
14.6


Ramos (B cell)
10.7
Lung fibroblast IL-13
17.1


ionomycin


B lymphocytes PWM
22.8
Lung fibroblast IFN
24.1




gamma


B lymphocytes CD40L
40.1
Dermal fibroblast
20.3


and IL-4

CCD1070 rest


EOL-1 dbcAMP
15.9
Dermal fibroblast
22.4




CCD1070 TNF alpha


EOL-1 dbcAMP
11.7
Dermal fibroblast
0.6


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
22.2
Dermal fibroblast IFN
10.6




gamma


Dendritic cells LPS
14.5
Dermal fibroblast IL-4
11.8


Dendritic cells anti-
23.5
IBD Colitis 2
7.3


CD40


Monocytes rest
37.9
IBD Crohn's
8.0


Monocytes LPS
15.8
Colon
54.0


Macrophages rest
10.2
Lung
9.7


Macrophages LPS
5.0
Thymus
39.5


HUVEC none
17.3
Kidney
63.7


HUVEC starved
11.8










[1816]

911





TABLE BPF










Panel 5 Islet











Rel. Exp. (%)

Rel. Exp. (%)



Ag3524, Run

Ag3524, Run


Tissue Name
242386392
Tissue Name
242386392













97457_Patient-
66.0
94709_Donor 2 AM - A_adipose
9.0


02go_adipose


97476_Patient-
10.7
94710_Donor 2 AM - B_adipose
9.8


07sk_skeletal muscle


97477_Patient-
9.4
94711_Donor 2 AM - C_adipose
8.1


07ut_uterus


97478_Patient-
7.8
94712_Donor 2 AD - A_adipose
17.8


07pl_placenta


99167_Bayer Patient
10.2
94713_Donor 2 AD - B_adipose
27.0


1


97482_Patient-
0.0
94714_Donor 2 AD - C_adipose
43.5


08ut_uterus


97483_Patient-
0.0
94742_Donor 3 U -
0.0


08pl_placenta

A_Mesenchymal Stem Cells


97486_Patient-
0.0
94743_Donor 3 U -
0.0


09sk_skeletal muscle

B_Mesenchymal Stem Cells


97487_Patient-
0.0
94730_Donor 3 AM - A_adipose
16.8


09ut_uterus


97488_Patient-
17.0
94731_Donor 3 AM - B_adipose
7.8


09pl_placenta


97492_Patient-
28.1
94732_Donor 3 AM - C_adipose
18.0


10ut_uterus


97493_Patient-
25.3
94733_Donor 3 AD - A_adipose
0.0


10pl_placenta


97495_Patient-
61.6
94734_Donor 3 AD - B_adipose
0.0


11go_adipose


97496_Patient-
28.5
94735_Donor 3 AD - C_adipose
18.9


11sk_skeletal muscle


97497_Patient-
16.2
77138_Liver_HepG2untreated
15.8


11ut_uterus


97498_Patient-
5.0
73556_Heart_Cardiac stromal
9.7


11pl_placenta

cells (primary)


97500_Patient-
100.0
81735_Small Intestine
62.9


12go_adipose


97501_Patient-
42.6
72409_Kidney_Proximal
24.0


12sk_skeletal muscle

Convoluted Tubule


97502_Patient-
41.8
82685_Small
32.8


12ut_uterus

intestine_Duodenum


97503_Patient-
0.0
90650_Adrenal_Adrenocortical
0.0


12pl_placenta

adenoma


94721_Donor 2 U -
0.0
72410_Kidney_HRCE
39.8


A_Mesenchymal


Stem Cells


94722_Donor 2 U -
0.0
72411_Kidney_HRE
21.8


B_Mesenchymal


Stem Cells


94723_Donor 2 U -
0.0
73139_Uterus_Uterine smooth
8.1


C_Mesenchymal

muscle cells


Stem Cells










[1817] CNS_neurodegeneration_v1.0 Summary: Ag3524 No differential expression of the CG59276-01 gene is detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. However, as observed in panel 1.4 this gene is expressed at low levels throughout the CNS, including in amygdala, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, this gene may play a role in central nervous system disorders such as Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[1818] General_screening_panel_v1.4 Summary: Ag3524 Expression of the CG59276-01 gene is highest in a sample derived from a brain and lung cancer cell lines (CTs=29). Thus, the expression of this gene could be used to distinguish these samples from the other samples in the panel. The CG59276-01 gene encodes a dihydroorotate dehydrogenase (DHODH) homolog. DHODH is an enzyme involved in the pathway for pyrimidine production. Drugs known to inhibit DHODH activity, such as brequinar sodium (Dup-785), have been shown to have anti-tumor activities (ref. 1). Therefore, therapeutic modulation of the activity of this gene encoded by this gene may be beneficial in the treatment of CNS and lung cancer. In addition, low to moderate expression of this gene is seen in all of the samples on this panel. Therefore, this gene may be playing an important role in cellular function.


[1819] This gene is expressed at low to moderate levels in a number of tissues with metabolic or endocrine function, including adipose, adrenal gland, gastrointestinal tract, pancreas, and skeletal muscle. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.


[1820] Recently, it has been demonstrated that down regulation of DHODH mRNA using RNA interference (RNAi) may inhibit growth of Plasmodium falciparum (ref 2). REFERENCES


[1821] 1. Braakhuis B J, van Dongen G A, Peters G J, van Walsum M, Snow G B (1990) Antitumor activity of brequinar sodium (Dup-785) against human head and neck squamous cell carcinoma xenografts. Cancer Lett 49(2):133-7.


[1822] 2. McRobert L, McConkey G A.(2002) RNA interference (RNAi) inhibits growth of Plasmodium falciparum. Mol Biochem Parasitol 119(2):273-8


[1823] Panel 2D Summary: Ag3524 The expression of this gene appears to be highest in a sample derived from a normal liver tissue (CT=30.3). In addition, there appears to be substantial expression in other samples derived from liver cancers and breast cancers. Thus, the expression of this gene could be used to distinguish normal liver tissue from other samples in the panel. Moreover, therapeutic modulation of this gene, through the use of small molecule drugs, protein therapeutics or antibodies could be of benefit in the treatment of liver or breast cancer.


[1824] Panel 4D Summary: Ag3524 Highest expression of the CG59276-01 gene is detected in resting primary Th1 cells (CT=30.03). In addition, the expression of this gene is significantly reduced in activated primary Th1 cells, suggesting a regulatory role for this gene in T-cell activation. The CG59276-01 encodes a dihydroorotate dehydrogenase, an enzyme involved in the pathway for pyrimidine production. Recently, an inhibitor of this enzyme, leflunomide has been shown to be an effective treatment for rheumatoid arthritis (ref 1). Therefore, therapeutics designed with the protein encoded for by this transcript could be important in regulating T cell function and treating T cell mediated diseases such as asthma, rheumatoid arthritis, psoriasis, IBD, and systemic lupus erythematosus.


[1825] Overall, this gene is expressed at low to moderate levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.4 and also suggests a role for the gene product in cell survival and proliferation.


[1826] Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.



REFERENCES

[1827] 1. Schattenkirchner M. (2000) The use of leflunomide in the treatment of rheumatoid arthritis: an experimental and clinical review. Immunopharmacology 47(2-3):291-3


[1828] Panel 5 Islet Summary: Ag3524 This gene has a low level of expression in adipose tissue (CTs=33-35). Thus, this gene product may be a small molecule drug for the treatment of obesity and obesity-related diseases, including Type 2 diabetes.


[1829] BQ. CG59268-01: K1AA2372


[1830] Expression of gene CG59268-01 was assessed using the primer-probe set Ag3523, described in Table BQA. Results of the RTQ-PCR runs are shown in Tables BQB and BQC.
912TABLE BQAProbe Name Ag3523StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-tactcttttggcttgatggaaa-3′22556608ProbeTET-5′-ccaacttctacgaccaggcagaaaa-3′-TAMRA25578609Reverse5′-gacaaagagttggtgcctcttt-3′22610610


[1831]

913





TABLE BQB










General_screening_panel_v1.4











Rel. Exp.

Rel. Exp.



(%) Ag3523,

(%) Ag3523,



Run

Run


Tissue Name
216874716
Tissue Name
216874716













Adipose
47.6
Renal ca. TK-10
62.9


Melanoma*
4.0
Bladder
25.2


Hs688(A).T


Melanoma*
0.0
Gastric ca. (liver met.)
40.1


Hs688(B).T

NCI-N87


Melanoma* M14
15.4
Gastric ca. KATO III
0.0


Melanoma*
0.8
Colon ca. SW-948
0.0


LOXIMVI


Melanoma* SK-
39.5
Colon ca. SW480
9.7


MEL-5


Squamous cell
0.0
Colon ca.* (SW480
10.2


carcinoma SCC-4

met) SW620


Testis Pool
35.8
Colon ca. HT29
27.2


Prostate ca.* (bone
8.5
Colon ca. HCT-116
52.5


met) PC-3


Prostate Pool
0.0
Colon ca. CaCo-2
31.2


Placenta
0.0
Colon cancer tissue
14.1


Uterus Pool
0.0
Colon ca. SW1116
0.0


Ovarian ca.
0.0
Colon ca. Colo-205
12.2


OVCAR-3


Ovarian ca. SK-
16.3
Colon ca. SW-48
0.0


OV-3


Ovarian ca.
10.3
Colon Pool
0.0


OVCAR-4


Ovarian ca.
47.6
Small Intestine Pool
3.9


OVCAR-5


Ovarian ca.
0.0
Stomach Pool
4.3


IGROV-1


Ovarian ca.
1.5
Bone Marrow Pool
0.0


OVCAR-8


Ovary
0.0
Fetal Heart
4.2


Breast ca. MCF-7
6.0
Heart Pool
4.2


Breast ca. MDA-
8.8
Lymph Node Pool
0.0


MB-231


Breast ca. BT 549
33.4
Fetal Skeletal Muscle
0.0


Breast ca. T47D
62.9
Skeletal Muscle Pool
5.1


Breast ca. MDA-N
8.8
Spleen Pool
0.0


Breast Pool
0.0
Thymus Pool
0.0


Trachea
0.0
CNS cancer
9.0




(glio/astro) U87-MG


Lung
0.0
CNS cancer
33.2




(glio/astro) U-118-MG


Fetal Lung
15.1
CNS cancer
23.5




(neuro; met) SK-N-AS


Lung ca. NCI-N417
3.5
CNS cancer (astro)
11.0




SF-539


Lung ca. LX-1
3.7
CNS cancer (astro)
13.8




SNB-75


Lung ca. NCI-H146
0.0
CNS cancer (glio)
20.7




SNB-19


Lung ca. SHP-77
11.0
CNS cancer (glio) SF-
30.1




295


Lung ca. A549
6.3
Brain (Amygdala)
0.0




Pool


Lung ca. NCI-H526
0.0
Brain (cerebellum)
0.0


Lung ca. NCI-H23
3.8
Brain (fetal)
4.5


Lung ca. NCI-H460
13.5
Brain (Hippocampus)
4.6




Pool


Lung ca. HOP-62
4.0
Cerebral Cortex Pool
0.0


Lung ca. NCI-H522
9.2
Brain (Substantia
4.4




nigra) Pool


Liver
4.5
Brain (Thalamus) Pool
0.0


Fetal Liver
0.0
Brain (whole)
0.0


Liver ca. HepG2
100.0
Spinal Cord Pool
0.0


Kidney Pool
6.5
Adrenal Gland
8.3


Fetal Kidney
17.9
Pituitary gland Pool
6.6


Renal ca. 786-0
38.7
Salivary Gland
16.3


Renal ca. A498
3.2
Thyroid (female)
0.0


Renal ca. ACHN
9.0
Pancreatic ca.
16.5




CAPAN2


Renal ca. UO-31
0.0
Pancreas Pool
11.3










[1832]

914





TABLE BQC










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3523, Run

Ag3523, Run


Tissue Name
166407138
Tissue Name
166407138













Secondary Th1 act
11.3
HUVEC IL-1beta
1.5


Secondary Th2 act
2.7
HUVEC IFN gamma
0.0


Secondary Tr1 act
9.5
HUVEC TNF alpha +
0.0




IFN gamma


Secondary Th1 rest
0.0
HUVEC TNF alpha +
0.0




IL4


Secondary Th2 rest
1.3
HUVEC IL-11
5.1


Secondary Tr1 rest
1.7
Lung Microvascular EC
0.0




none


Primary Th1 act
13.1
Lung Microvascular EC
0.0




TNF alpha + IL-1beta


Primary Th2 act
10.8
Microvascular Dermal
1.0




EC none


Primary Tr1 act
7.5
Microsvasular Dermal
1.6




EC TNF alpha + IL-1beta


Primary Th1 rest
1.4
Bronchial epithelium
0.0




TNF alpha + IL-1beta


Primary Th2 rest
0.0
Small airway epithelium
1.0




none


Primary Tr1 rest
2.6
Small airway epithelium
4.4




TNF alpha + IL-1beta


CD45RA CD4
0.0
Coronery artery SMC rest
0.0


lymphocyte act


CD45RO CD4
8.0
Coronery artery SMC
0.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
0.0
Astrocytes rest
0.0


Secondary CD8
1.5
Astrocytes TNF alpha +
0.0


lymphocyte rest

IL-1beta


Secondary CD8
3.1
KU-812 (Basophil) rest
0.0


lymphocyte act


CD4 lymphocyte none
1.0
KU-812 (Basophil)
8.1




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
3.7
CCD1106
4.0


CD95 CH11

(Keratinocytes) none


LAK cells rest
7.2
CCD1106
2.2




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
0.0
Liver cirrhosis
15.3


LAK cells IL-2 + IL-12
8.9
Lupus kidney
5.0


LAK cells IL-2 + IFN
12.2
NCI-H292 none
1.0


gamma


LAK cells IL-2 + IL-18
4.7
NCI-H292 IL-4
0.6


LAK cells
1.4
NCI-H292 IL-9
1.6


PMA/ionomycin


NK Cells IL-2 rest
7.9
NCI-H292 IL-13
1.5


Two Way MLR 3 day
0.0
NCI-H292 IFN gamma
1.2


Two Way MLR 5 day
0.0
HPAEC none
0.0


Two Way MLR 7 day
0.0
HPAEC TNF alpha + IL-
0.0




1beta


PBMC rest
5.5
Lung fibroblast none
0.0


PBMC PWM
2.6
Lung fibroblast TNF
0.0




alpha + IL-1beta


PBMC PHA-L
0.0
Lung fibroblast IL-4
3.9


Ramos (B cell) none
0.0
Lung fibroblast IL-9
0.0


Ramos (B cell)
0.0
Lung fibroblast IL-13
0.0


ionomycin


B lymphocytes PWM
8.2
Lung fibroblast IFN
0.0




gamma


B lymphocytes CD40L
1.5
Dermal fibroblast
0.0


and IL-4

CCD1070 rest


EOL-1 dbcAMP
4.5
Dermal fibroblast
13.9




CCD1070 TNF alpha


EOL-1 dbcAMP
10.8
Dermal fibroblast
0.4


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
0.0
Dermal fibroblast IFN
0.0




gamma


Dendritic cells LPS
0.0
Dermal fibroblast IL-4
0.0


Dendritic cells anti-
0.0
IBD Colitis 2
0.0


CD40


Monocytes rest
11.5
IBD Crohn's
66.0


Monocytes LPS
6.4
Colon
100.0


Macrophages rest
4.5
Lung
0.0


Macrophages LPS
1.4
Thymus
38.4


HUVEC none
1.9
Kidney
0.0


HUVEC starved
1.6










[1833] CNS_neurodegeneration_v1.0 Summary: Ag3523 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1834] General_screening_panel_v1.4 Summary: Ag3523 Expression of the CG59268-01 gene is highest in sample derived from liver cancer cell line (CT=32.55). Therefore, expression of this gene may be used to distinguish liver cancers from the other samples on this panel. In addition, low levels of expression of this gene are also observed in one of the ovarian cancer, 2 of the breast cancer, 2 of the renal cancer, bladder, gastric cancer, 3 of the colon cancer, and 4 of the CNS cancer samples. Therefore, therapeutic modulation of the activity of this gene product may be beneficial in the treatment of these cancers.


[1835] Among the tissues with metabolic or endocrine function, this gene is expressed at low levels in adipose tissue sample. Adipose tissue has several crucial roles including (i) mobilization from stores of fatty acids as an energy source, (ii) catabolism of lipoproteins such as very-low-density lipoprotein and (iii) synthesis and release of hormonal signals such as leptin and interleukin-6 (Coppack et al., 2001). Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity, hyperlipidemia, and insulin resistance.



REFERENCES

[1836] 1. Coppack S W, Patel J N, Lawrence V J. (2001) Nutritional regulation of lipid metabolism in human adipose tissue. Exp Clin Endocrinol Diabetes; 109(Suppl 2):S202-S214


[1837] Panel 4D Summary: Ag3523 Expression of the CG59268-01 gene is highest in sample derived from colon (CT=31.56). Therefore, expression of this gene may be used to distinguish colon sample from the other samples on this panel. In addition, significant expression of this gene is also observed in IBD Crohn's sample (CT=32.16). Thus, expression of this gene in colon and Crohn's sample can be used to distinguish these two samples from IBD Colitis 2 sample. In addition, therapeutic modulation of the activity of this gene product may be beneficial in the treatment of IBD Crohn's disease.


[1838] BR. CG59549-01: H326 Like


[1839] Expression of gene CG59549-01 was assessed using the primer-probe set Ag3464, described in Table BRA. Results of the RTQ-PCR runs are shown in Tables BRB and BRC.
915TABLE BRAProbe Name Ag3464StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-gtgcgtcacctgttacagaga-3′211678611ProbeTET-5′-ctcatcaacccggctggagagatcat-3′-TAMRA261700612Reverse5′-ctcttcttcatctgggaactca-3′221731613


[1840]

916





TABLE BRB










General_screening_panel_v1.4











Rel. Exp.

Rel. Exp.



(%) Ag3464,

(%) Ag3464,



Run

Run


Tissue Name
217067408
Tissue Name
217067408













Adipose
0.0
Renal ca. TK-10
0.0


Melanoma*
0.0
Bladder
0.0


Hs688(A).T


Melanoma*
0.0
Gastric ca. (liver met.)
1.6


Hs688(B).T

NCI-N87


Melanoma* M14
1.0
Gastric ca. KATO III
2.1


Melanoma*
0.0
Colon ca. SW-948
0.0


LOXIMVI


Melanoma* SK-
23.8
Colon ca. SW480
2.6


MEL-5


Squamous cell
0.0
Colon ca.* (SW480
0.0


carcinoma SCC-4

met) SW620


Testis Pool
22.8
Colon ca. HT29
0.0


Prostate ca.* (bone
0.0
Colon ca. HCT-116
0.0


met) PC-3


Prostate Pool
0.0
Colon ca. CaCo-2
0.0


Placenta
0.0
Colon cancer tissue
0.3


Uterus Pool
0.0
Colon ca. SW1116
0.0


Ovarian ca.
0.0
Colon ca. Colo-205
0.0


OVCAR-3


Ovarian ca. SK-
1.0
Colon ca. SW-48
0.0


OV-3


Ovarian ca.
0.0
Colon Pool
3.3


OVCAR-4


Ovarian ca.
0.0
Small Intestine Pool
0.9


OVCAR-5


Ovarian ca.
0.0
Stomach Pool
0.0


IGROV-1


Ovarian ca.
4.8
Bone Marrow Pool
0.0


OVCAR-8


Ovary
0.0
Fetal Heart
0.0


Breast ca. MCF-7
0.0
Heart Pool
0.0


Breast ca. MDA-
0.0
Lymph Node Pool
0.0


MB-231


Breast ca. BT 549
0.0
Fetal Skeletal Muscle
0.0


Breast ca. T47D
4.9
Skeletal Muscle Pool
0.0


Breast ca. MDA-N
1.1
Spleen Pool
0.0


Breast Pool
2.2
Thymus Pool
0.7


Trachea
0.0
CNS cancer
0.0




(glio/astro) U87-MG


Lung
0.0
CNS cancer
20.4




(glio/astro) U-118-MG


Fetal Lung
0.0
CNS cancer
0.0




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.0
CNS cancer (astro)
0.0




SF-539


Lung ca. LX-1
0.0
CNS cancer (astro)
0.0




SNB-75


Lung ca. NCI-H146
2.0
CNS cancer (glio)
0.0




SNB-19


Lung ca. SHP-77
0.7
CNS cancer (glio) SF-
100.0




295


Lung ca. A549
0.6
Brain (Amygdala)
1.1




Pool


Lung ca. NCI-H526
0.0
Brain (cerebellum)
0.0


Lung ca. NCI-H23
0.0
Brain (fetal)
0.0


Lung ca. NCI-H460
0.0
Brain (Hippocampus)
0.0




Pool


Lung ca. HOP-62
2.6
Cerebral Cortex Pool
0.0


Lung ca. NCI-H522
0.0
Brain (Substantia
0.8




nigra) Pool


Liver
0.0
Brain (Thalamus) Pool
1.1


Fetal Liver
0.0
Brain (whole)
0.0


Liver ca. HepG2
0.0
Spinal Cord Pool
0.8


Kidney Pool
0.0
Adrenal Gland
2.0


Fetal Kidney
3.2
Pituitary gland Pool
0.0


Renal ca. 786-0
0.0
Salivary Gland
0.0


Renal ca. A498
0.0
Thyroid (female)
0.0


Renal ca. ACHN
0.0
Pancreatic ca.
0.0




CAPAN2


Renal ca. UO-31
0.0
Pancreas Pool
1.8










[1841]

917





TABLE BRC










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3464, Run

Ag3464, Run


Tissue Name
166417099
Tissue Name
166417099













Secondary Th1 act
0.0
HUVEC IL-1beta
0.0


Secondary Th2 act
0.0
HUVEC IFN gamma
0.0


Secondary Tr1 act
2.5
HUVEC TNF alpha +
0.0




IFN gamma


Secondary Th1 rest
0.0
HUVEC TNF alpha +
0.0




IL4


Secondary Th2 rest
0.0
HUVEC IL-11
0.0


Secondary Tr1 rest
0.0
Lung Microvascular EC
0.0




none


Primary Th1 act
0.0
Lung Microvascular EC
0.0




TNF alpha + IL-1beta


Primary Th2 act
0.0
Microvascular Dermal
0.0




EC none


Primary Tr1 act
0.0
Microsvasular Dermal
0.0




EC TNF alpha + IL-1beta


Primary Th1 rest
0.0
Bronchial epithelium
0.0




TNF alpha + IL-1beta


Primary Th2 rest
0.0
Small airway epithelium
0.0




none


Primary Tr1 rest
0.0
Small airway epithelium
0.0




TNF alpha + IL-1beta


CD45RA CD4
0.0
Coronery artery SMC rest
0.0


lymphocyte act


CD45RO CD4
0.0
Coronery artery SMC
0.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
0.0
Astrocytes rest
0.0


Secondary CD8
0.0
Astrocytes TNF alpha +
0.0


lymphocyte rest

IL-1beta


Secondary CD8
0.0
KU-812 (Basophil) rest
0.0


lymphocyte act


CD4 lymphocyte none
0.0
KU-812 (Basophil)
12.0




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
5.9
CCD1106
0.0


CD95 CH11

(Keratinocytes) none


LAK cells rest
0.0
CCD1106
0.0




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
0.0
Liver cirrhosis
100.0


LAK cells IL-2 + IL-12
0.0
Lupus kidney
0.0


LAK cells IL-2 + IFN
0.0
NCI-H292 none
0.0


gamma


LAK cells IL-2 + IL-18
0.0
NCI-H292 IL-4
0.0


LAK cells
0.0
NCI-H292 IL-9
10.0


PMA/ionomycin


NK Cells IL-2 rest
0.0
NCI-H292 IL-13
0.0


Two Way MLR 3 day
0.0
NCI-H292 IFN gamma
3.2


Two Way MLR 5 day
0.0
HPAEC none
0.0


Two Way MLR 7 day
0.0
HPAEC TNF alpha + IL-
0.0




1beta


PBMC rest
0.0
Lung fibroblast none
7.0


PBMC PWM
0.0
Lung fibroblast TNF
0.0




alpha + IL-1beta


PBMC PHA-L
0.0
Lung fibroblast IL-4
0.0


Ramos (B cell) none
0.0
Lung fibroblast IL-9
0.0


Ramos (B cell)
0.0
Lung fibroblast IL-13
0.0


ionomycin


B lymphocytes PWM
0.0
Lung fibroblast IFN
0.0




gamma


B lymphocytes CD40L
0.0
Dermal fibroblast
0.0


and IL-4

CCD1070 rest


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0




CCD1070 TNF alpha


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
0.0
Dermal fibroblast IFN
0.0




gamma


Dendritic cells LPS
0.0
Dermal fibroblast IL-4
0.0


Dendritic cells anti-
0.0
IBD Colitis 2
0.0


CD40


Monocytes rest
0.0
IBD Crohn's
6.3


Monocytes LPS
0.0
Colon
27.4


Macrophages rest
0.0
Lung
3.8


Macrophages LPS
0.0
Thymus
0.0


HUVEC none
0.0
Kidney
0.0


HUVEC starved
0.0










[1842] CNS_neurodegeneration_v1.0 Summary: Ag3464 Expression of the CG59549-01 gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1843] General_screening_panel_v1.4 Summary: Ag3464 Expression of the CG59549-01 gene is highest in a CNS cancer (glio) SF-295 sample (CT=31.15). Thus, the expression of this gene could be used to distinguish this sample from the other samples in the panel. In addition, low to moderate expression of this gene is detected in a melanoma and a CNS cancer sample. Therefore, therapeutic modulation of this gene or its protein product may be beneficial in the treatment of melanoma and CNS cancer.


[1844] Panel 4D Summary: Ag3464 Low but significant expression of the CG59549-01 gene is detected exclusively in liver cirrhosis sample (CT=33.4). Therefore, expression of this gene may be used to distinguish liver cirrhosis from the other samples on this panel. Furthermore, expression of this gene is not detected in normal liver in Panel 1.3D, suggesting that its expression is unique to liver cirrhosis. Therefore, antibodies or small molecule therapeutics could reduce or inhibit fibrosis that occurs in liver cirrhosis. In addition, antibodies to this gene product could also be used for the diagnosis of liver cirrhosis.


[1845] BS. CG59641-01: Acetyl-Coa Carboxylase 2


[1846] Expression of gene CG59641-01 was assessed using the primer-probe set Ag3502, described in Table BSA. Results of the RTQ-PCR runs are shown in Table BSB.
918TABLE BSAProbe Name Ag3502StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-ctccctacgtcaccaaggat-3′205090614ProbeTET-5′-aagcgattccaggcccagaccct-3′-TAMRA235122615Reverse5′-ccgggaagtcatagatgtaggt-3′-225152616


[1847]

919





TABLE BSB










General_screening_panel_v1.4











Rel. Exp.

Rel. Exp.



(%) Ag3502,

(%) Ag3502,



Run

Run


Tissue Name
217131537
Tissue Name
217131537













Adipose
100.0
Renal ca. TK-10
6.6


Melanoma*
1.5
Bladder
14.2


Hs688(A).T


Melanoma*
1.4
Gastric ca. (liver met.)
11.6


Hs688(B).T

NCI-N87


Melanoma* M14
7.2
Gastric ca. KATO III
4.2


Melanoma*
0.0
Colon ca. SW-948
0.5


LOXIMVI


Melanoma* SK-
14.8
Colon ca. SW480
7.8


MEL-5


Squamous cell
0.2
Colon ca.* (SW480
5.8


carcinoma SCC-4

met) SW620


Testis Pool
10.0
Colon ca. HT29
1.0


Prostate ca.* (bone
19.9
Colon ca. HCT-116
5.8


met) PC-3


Prostate Pool
12.9
Colon ca. CaCo-2
8.2


Placenta
1.9
Colon cancer tissue
7.6


Uterus Pool
9.2
Colon ca. SW1116
2.0


Ovarian ca.
6.6
Colon ca. Colo-205
9.0


OVCAR-3


Ovarian ca. SK-
12.2
Colon ca. SW-48
1.7


OV-3


Ovarian ca.
1.9
Colon Pool
20.7


OVCAR-4


Ovarian ca.
8.5
Small Intestine Pool
27.9


OVCAR-5


Ovarian ca.
1.2
Stomach Pool
28.7


IGROV-1


Ovarian ca.
1.7
Bone Marrow Pool
8.0


OVCAR-8


Ovary
12.1
Fetal Heart
30.6


Breast ca. MCF-7
63.7
Heart Pool
16.7


Breast ca. MDA-
4.5
Lymph Node Pool
18.8


MB-231


Breast ca. BT 549
1.8
Fetal Skeletal Muscle
5.4


Breast ca. T47D
10.8
Skeletal Muscle Pool
66.0


Breast ca. MDA-N
2.3
Spleen Pool
14.9


Breast Pool
39.0
Thymus Pool
16.4


Trachea
15.3
CNS cancer
5.8




(glio/astro) U87-MG


Lung
5.6
CNS cancer
9.1




(glio/astro) U-118-MG


Fetal Lung
13.6
CNS cancer
5.0




(neuro; met) SK-N-AS


Lung ca. NCI-N417
2.3
CNS cancer (astro)
3.1




SF-539


Lung ca. LX-1
6.4
CNS cancer (astro)
3.7




SNB-75


Lung ca. NCI-H146
2.2
CNS cancer (glio)
1.3




SNB-19


Lung ca. SHP-77
2.8
CNS cancer (glio)
8.1




SF-295


Lung ca. A549
10.0
Brain (Amygdala)
6.2




Pool


Lung ca. NCI-H526
0.9
Brain (cerebellum)
13.0


Lung ca. NCI-H23
26.6
Brain (fetal)
4.2


Lung ca. NCI-H460
3.9
Brain (Hippocampus)
7.5




Pool


Lung ca. HOP-62
1.4
Cerebral Cortex Pool
8.4


Lung ca. NCI-H522
13.5
Brain (Substantia
7.0




nigra) Pool


Liver
23.2
Brain (Thalamus) Pool
10.2


Fetal Liver
11.7
Brain (whole)
8.8


Liver ca. HepG2
6.6
Spinal Cord Pool
9.1


Kidney Pool
38.7
Adrenal Gland
50.0


Fetal Kidney
10.4
Pituitary gland Pool
7.4


Renal ca. 786-0
1.5
Salivary Gland
11.3


Renal ca. A498
1.4
Thyroid (female)
5.1


Renal ca. ACHN
3.0
Pancreatic ca.
1.7




CAPAN2


Renal ca. UO-31
2.5
Pancreas Pool
17.0










[1848] General_screening_panel_v1.4 Summary: Ag3502 The CG59641-01 encodes an acetyl-CoA carboxylase 2 (ACC2) protein. Expression of this gene is highest in adipose tissue (CT=25.5). High levels of expression of this gene are also detected in other tissues with metabolic or endocrine function such as pancreas, adrenal gland, gastrointestinal tract, heart, skeletal muscle, and thyroid. Acetyl-coenzyme A (acetyl-CoA) carboxylase (ACC) catalyzes the synthesis of malonyl-CoA, a metabolite that plays a pivotal role in the synthesis and oxidation of fatty. Hence, ACC links fatty acid and carbohydrate metabolism through the shared intermediate acetyl-CoA, the product of pyruvate dehydrogenase. It has been shown recently that mutations in ACC2 gene lead to loss of body fat in a normal caloric intake in mouse (Abu-Elheiga et al., 2001). Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.


[1849] Low to moderate expression of this gene is also detected in most of the samples used in this panel suggesting the possibility of a wider role in intercellular signaling for this molecule.


[1850] Among tissues that originate in the central nervous system, this gene is expressed in all regions represented on this panel. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.


[1851] In addition, significantly higher levels of expression are seen in a breast cancer cell line. Thus, expression of this gene could be used to differentiate between this sample and other samples on this panel and as a marker to detect the presence of breast cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of breast cancer.



REFERENCES

[1852] 1. Abu-Elheiga L, Matzuk M M, Abo-Hashema K A, Wakil S J. (2001) Continuous fatty acid oxidation and reduced fat storage in mice lacking acetyl-CoA carboxylase 2. Science Mar. 30, 2001;291(5513):2613-6


[1853] BT. CG59630-01: Midnolin


[1854] Expression of gene CG59630-01 was assessed using the primer-probe set Ag3425, described in Table BTA. Results of the RTQ-PCR runs are shown in Tables BTB, BTC and BTD.
920TABLE BTAProbe Name Ag3425SEQ IDPrimersSequencesLengthStart PositionNO:Forward5′-aagctgaccttggtacccac-3′20295617ProbeTET-5′-ctcatgtctcaggcctcaaggcc-3′-TAMRA23328618Reverse5′-ctctcgagagcttgcatcac-3′20361619


[1855]

921





TABLE BTB










CNS_neurodegeneration_v1.0











Rel. Exp.

Rel. Exp.



(%) Ag3425,

(%) Ag3425,



Run

Run


Tissue Name
210350911
Tissue Name
210350911













AD 1 Hippo
18.6
Control (Path) 3
14.0




Temporal Ctx


AD 2 Hippo
44.1
Control (Path) 4
25.0




Temporal Ctx


AD 3 Hippo
11.3
AD 1 Occipital Ctx
13.6


AD 4 Hippo
19.3
AD 2 Occipital Ctx
0.0




(Missing)


AD 5 Hippo
53.2
AD 3 Occipital Ctx
11.5


AD 6 Hippo
100.0
AD 4 Occipital Ctx
24.7


Control 2 Hippo
47.0
AD 5 Occipital Ctx
53.2


Control 4 Hippo
38.2
AD 6 Occipital Ctx
80.7


Control (Path) 3
10.5
Control 1 Occipital
19.9


Hippo

Ctx


AD 1 Temporal
17.3
Control 2 Occipital
49.3


Ctx

Ctx


AD 2 Temporal
33.7
Control 3 Occipital
31.2


Ctx

Ctx


AD 3 Temporal
10.4
Control 4 Occipital
13.9


Ctx

Ctx


AD 4 Temporal
19.1
Control (Path) 1
81.2


Ctx

Occipital Ctx


AD 5 Inf Temporal
49.3
Control (Path) 2
11.0


Ctx

Occipital Ctx


AD 5 Sup
45.4
Control (Path) 3
8.4


Temporal Ctx

Occipital Ctx


AD 6 Inf Temporal
97.3
Control (Path) 4
19.6


Ctx

Occipital Ctx


AD 6 Sup
85.9
Control 1 Parietal
18.8


Temporal Ctx

Ctx


Control 1
20.3
Control 2 Parietal
29.9


Temporal Ctx

Ctx


Control 2
59.9
Control 3 Parietal
32.3


Temporal Ctx

Ctx


Control 3
32.3
Control (Path) 1
91.4


Temporal Ctx

Parietal Ctx


Control 3
17.4
Control (Path) 2
32.3


Temporal Ctx

Parietal Ctx


Control (Path) 1
70.7
Control (Path) 3
7.7


Temporal Ctx

Parietal Ctx


Control (Path) 2
27.5
Control (Path) 4
45.1


Temporal Ctx

Parietal Ctx










[1856]

922





TABLE BTC










General_screening_panel_v1.4











Rel. Exp.

Rel. Exp.



(%) Ag3425,

(%) Ag3425,



Run

Run


Tissue Name
217049295
Tissue Name
217049295













Adipose
17.8
Renal ca. TK-10
26.4


Melanoma*
15.5
Bladder
16.0


Hs688(A).T


Melanoma*
19.5
Gastric ca. (liver met.)
26.6


Hs688(B).T

NCI-N87


Melanoma* M14
10.5
Gastric ca. KATO III
23.0


Melanoma*
15.7
Colon ca. SW-948
11.6


LOXIMVI


Melanoma* SK-
8.0
Colon ca. SW480
27.5


MEL-5


Squamous cell
27.2
Colon ca.* (SW480
15.3


carcinoma SCC-4

met) SW620


Testis Pool
5.6
Colon ca. HT29
15.2


Prostate ca.* (bone
18.7
Colon ca. HCT-116
40.6


met) PC-3


Prostate Pool
3.3
Colon ca. CaCo-2
41.8


Placenta
16.8
Colon cancer tissue
19.6


Uterus Pool
2.6
Colon ca. SW1116
9.5


Ovarian ca.
27.7
Colon ca. Colo-205
41.5


OVCAR-3


Ovarian ca. SK-
58.2
Colon ca. SW-48
6.8


OV-3


Ovarian ca.
4.0
Colon Pool
5.9


OVCAR-4


Ovarian ca.
27.2
Small Intestine Pool
6.6


OVCAR-5


Ovarian ca.
30.1
Stomach Pool
42.9


IGROV-1


Ovarian ca.
19.3
Bone Marrow Pool
2.7


OVCAR-8


Ovary
7.6
Fetal Heart
9.0


Breast ca. MCF-7
37.1
Heart Pool
5.7


Breast ca. MDA-
15.3
Lymph Node Pool
6.5


MB-231


Breast ca. BT 549
51.1
Fetal Skeletal Muscle
6.6


Breast ca. T47D
100.0
Skeletal Muscle Pool
17.4


Breast ca. MDA-N
8.3
Spleen Pool
11.2


Breast Pool
41.8
Thymus Pool
8.0


Trachea
15.9
CNS cancer
46.3




(glio/astro) U87-MG


Lung
2.6
CNS cancer
20.7




(glio/astro) U-118-MG


Fetal Lung
55.5
CNS cancer
29.1




(neuro; met) SK-N-AS


Lung ca. NCI-N417
43.5
CNS cancer (astro)
13.8




SF-539


Lung ca. LX-1
23.5
CNS cancer (astro)
36.9




SNB-75


Lung ca. NCI-H146
5.8
CNS cancer (glio)
29.1




SNB-19


Lung ca. SHP-77
11.7
CNS cancer (glio)
73.7




SF-295


Lung ca. A549
21.5
Brain (Amygdala)
5.3




Pool


Lung ca. NCI-H526
15.7
Brain (cerebellum)
14.6


Lung ca. NCI-H23
12.9
Brain (fetal)
20.6


Lung ca. NCI-H460
49.3
Brain (Hippocampus)
4.6




Pool


Lung ca. HOP-62
10.1
Cerebral Cortex Pool
4.9


Lung ca. NCI-H522
16.2
Brain (Substantia
10.4




nigra) Pool


Liver
1.3
Brain (Thalamus) Pool
6.1


Fetal Liver
9.3
Brain (whole)
45.1


Liver ca. HepG2
29.7
Spinal Cord Pool
5.8


Kidney Pool
8.0
Adrenal Gland
13.6


Fetal Kidney
11.3
Pituitary gland Pool
6.8


Renal ca. 786-0
23.0
Salivary Gland
4.6


Renal ca. A498
18.2
Thyroid (female)
13.9


Renal ca. ACHN
13.6
Pancreatic ca.
7.6




CAPAN2


Renal ca. UO-31
28.5
Pancreas Pool
14.0










[1857]

923





TABLE BTD










Panel 4.1D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3425, Run

Ag3425, Run


Tissue Name
169839020
Tissue Name
169839020













Secondary Th1 act
20.6
HUVEC IL-1beta
46.7


Secondary Th2 act
30.6
HUVEC IFN gamma
23.3


Secondary Tr1 act
32.1
HUVEC TNF alpha +
13.3




IFN gamma


Secondary Th1 rest
18.2
HUVEC TNF alpha +
22.8




IL4


Secondary Th2 rest
23.8
HUVEC IL-11
22.5


Secondary Tr1 rest
12.6
Lung Microvascular EC
37.9




none


Primary Th1 act
2.8
Lung Microvascular EC
22.2




TNF alpha + IL-1beta


Primary Th2 act
24.7
Microvascular Dermal
24.1




EC none


Primary Tr1 act
20.0
Microsvasular Dermal
21.2




EC TNF alpha + IL-1beta


Primary Th1 rest
18.6
Bronchial epithelium
26.6




TNF alpha + IL-1beta


Primary Th2 rest
19.5
Small airway epithelium
23.5




none


Primary Tr1 rest
22.4
Small airway epithelium
27.2




TNF alpha + IL-1beta


CD45RA CD4
17.7
Coronery artery SMC rest
22.1


lymphocyte act


CD45RO CD4
19.8
Coronery artery SMC
20.2


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
14.1
Astrocytes rest
24.7


Secondary CD8
23.8
Astrocytes TNF alpha +
17.8


lymphocyte rest

IL-1beta


Secondary CD8
12.2
KU-812 (Basophil) rest
16.5


lymphocyte act


CD4 lymphocyte none
6.5
KU-812 (Basophil)
36.6




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
15.2
CCD1106
40.1


CD95 CH11

(Keratinocytes) none


LAK cells rest
34.2
CCD1106
41.8




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
24.5
Liver cirrhosis
20.0


LAK cells IL-2 + IL-12
21.6
NCI-H292 none
41.2


LAK cells IL-2 + IFN
23.2
NCI-H292 IL-4
58.6


gamma


LAK cells IL-2 + IL-18
22.2
NCI-H292 IL-9
61.6


LAK cells
97.3
NCI-H292 IL-13
47.6


PMA/ionomycin


NK Cells IL-2 rest
28.7
NCI-H292 IFN gamma
54.0


Two Way MLR 3 day
32.5
HPAEC none
16.6


Two Way MLR 5 day
30.1
HPAEC TNF alpha + IL-
20.7




1beta


Two Way MLR 7 day
18.7
Lung fibroblast none
46.0


PBMC rest
27.9
Lung fibroblast TNF
20.2




alpha + IL-1beta


PBMC PWM
25.3
Lung fibroblast IL-4
47.0


PBMC PHA-L
22.7
Lung fibroblast IL-9
52.1


Ramos (B cell) none
25.5
Lung fibroblast IL-13
45.1


Ramos (B cell)
23.5
Lung fibroblast IFN
50.0


ionomycin

gamma


B lymphocytes PWM
17.8
Dermal fibroblast
28.3




CCD1070 rest


B lymphocytes CD40L
23.8
Dermal fibroblast
37.1


and IL-4

CCD1070 TNF alpha


EOL-1 dbcAMP
34.4
Dermal fibroblast
13.3




CCD1070 IL-1beta


EOL-1 dbcAMP
87.7
Dermal fibroblast IFN
28.5


PMA/ionomycin

gamma


Dendritic cells none
32.3
Dermal fibroblast IL-4
26.2


Dendritic cells LPS
21.5
Dermal Fibroblasts rest
26.6


Dendritic cells anti-
32.8
Neutrophils TNFa + LPS
33.7


CD40


Monocytes rest
54.3
Neutrophils rest
100.0


Monocytes LPS
93.3
Colon
18.4


Macrophages rest
23.8
Lung
28.7


Macrophages LPS
36.1
Thymus
28.1


HUVEC none
24.7
Kidney
14.0


HUVEC starved
38.4










[1858] CNS_neurodegeneration_v1.0 Summary: Ag3425 This panel confirms the expression of this gene at low levels in the brain in an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.


[1859] General_screening_panel_v1.4 Summary: Ag3425 The CG59630-01 gene is a homologue of mouse midnoline (midbrain nucleolar protein). Its expression is moderate to high across all of the samples on this panel, with highest expression in a breast cancer cell line (CT=25.3). The widespread expression suggests that this gene may play an important role in cellular function. In mouse, the expression of this gene is developmentally regulated: it is strongly expressed at the mesencephalon (midbrain) of the embryo and is involved in regulation of genes related to neurogenesis in the nucleolus (Tsukahara et al., 2000). Based on the gene's expression in all CNS regions examined, this gene may therefore play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[1860] Among tissues with metabolic function, this gene is expressed at moderate to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.



REFERENCE

[1861] 1. Tsukahara M, Suemori H, Noguchi S, Ji Z S, Tsunoo H. (2000) Novel nucleolar protein, midnolin, is expressed in the mesencephalon during mouse development. Gene Aug. 22, 2000;254(1-2):45-55


[1862] Panel 4.1D Summary: Ag3425 The CG59630-01 gene is a homologue of mouse midnoline (midbrain nucleolar protein). Its expression is moderate to high across all of the samples on this panel, with highest expression in resting neutrophils (CT=29.1). In addition, this gene is expressed at high to moderate levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.4 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.


[1863] BU. CG59561-01: Cytosolic Acyl Coenzyme a Thioester Hydrolase


[1864] Expression of gene CG59561-01 was assessed using the primer-probe set Ag3424, described in Table BUA. Results of the RTQ-PCR runs are shown in Tables BUB, BUC and BUD.
924TABLE BUAProbe Name Ag3424StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-aagctgaccaataaggccac-3′20345620ProbeTET-5′-gtggacaaggtcctcgaagagcctc-3′-TAMRA25396621Reverse5′-ctgccggaaatacacaacag-3′20421622


[1865]

925





TABLE BUB










CNS_neurodegeneration_v1.0











Rel. Exp.

Rel. Exp. (%)



(%) Ag3424

(%) Ag3424



Run

Run


Tissue Name
210350585
Tissue Name
210350585













AD 1 Hippo
8.8
Control (Path) 3
1.5




Temporal Ctx


AD 2 Hippo
16.7
Control (Path) 4
25.5




Temporal Ctx


AD 3 Hippo
2.7
AD 1 Occipital
3.7




Ctx


AD 4 Hippo
4.7
AD 2 Occipital
0.0




Ctx (Missing)


AD 5 hippo
100.0
AD 3 Occipital
2.0




Ctx


AD 6 Hippo
34.6
AD 4 Occipital
8.5




Ctx


Control 2 Hippo
44.8
AD 5 Occipital
11.7




Ctx


Control 4 Hippo
2.2
AD 6 Occipital
90.8




Ctx


Control (Path) 3
2.0
Control 1 Occipital
0.8


Hippo

Ctx


AD 1 Temporal Ctx
2.4
Control 2 Occipital
84.1




Ctx


AD 2 Temporal Ctx
16.6
Control 3 Occipital
5.1




Ctx


AD 3 Temporal Ctx
2.1
Control 4 Occipital
1.3




Ctx


AD 4 Temporal Ctx
8.6
Control (Path) 1
96.6




Occipital Ctx


AD 5 Inf Temporal
62.9
Control (Path) 2
5.7


Ctx

Occipital Ctx


AD 5 SupTemporal
28.3
Control (Path) 3
0.5


Ctx

Occipital Ctx


AD 6 Inf Temporal
26.6
Control (Path) 4
8.8


Ctx

Occipital Ctx


AD 6 Sup Temporal
22.1
Control 1 Parietal
2.0


Ctx

Ctx


Control 1 Temporal
1.2
Control 2 Parietal
22.1


Ctx

Ctx


Control 2 Temporal
65.1
Control 3 Parietal
19.9


Ctx

Ctx


Control 3 Temporal
8.7
Control (Path) 1
94.0


Ctx

Parietal Ctx


Control 4 Temporal
2.4
Control (Path) 2
14.0


Ctx

Parietal Ctx


Control (Path) 1
61.1
Control (Path) 3
0.9


Temporal Ctx

Parietal Ctx


Control (Path) 2
28.3
Control (Path) 4
39.0


Temporal Ctx

Parietal Ctx










[1866]

926





TABLE BUC










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3424, Run

Ag3424, Run


Tissue Name
166385382
Tissue Name
166385382













Secondary Th1 act
62.9
HUVEC IL-1beta
4.0


Secondary Th2 act
37.9
HUVEC IFN gamma
10.7


Secondary Tr1 act
68.8
HUVEC TNF alpha +
18.6




IFN gamma


Secondary Th1 rest
4.2
HUVEC TNF alpha +
15.5




IL4


Secondary Th2 rest
12.1
HUVEC IL-11
10.2


Secondary Tr1 rest
4.4
Lung Microvascular EC
28.7




none


Primary Th1 act
66.9
Lung Microvascular EC
25.7




TNF alpha + IL-1beta


Primary Th2 act
61.1
Microvascular Dermal
36.3




EC none


Primary Tr1 act
43.2
Microsvasular Dermal
20.3




EC TNF alpha + IL-1beta


Primary Th1 rest
30.1
Bronchial epithelium
25.5




TNF alpha + IL-1beta


Primary Th2 rest
17.4
Small airway epithelium
19.5




none


Primary Tr1 rest
15.9
Small airway epithelium
52.1




TNF alpha + IL-1beta


CD45RA CD4
14.8
Coronery artery SMC rest
14.8


lymphocyte act


CD45RO CD4
37.6
Coronery artery SMC
8.3


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
43.8
Astrocytes rest
13.9


Secondary CD8
49.7
Astrocytes TNF alpha +
13.3


lymphocyte rest

IL-1beta


Secondary CD8
24.1
KU-812 (Basophil) rest
23.8


lymphocyte act


CD4 lymphocyte none
0.9
KU-812 (Basophil)
51.4




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
9.0
CCD1106
62.4


CD95 CH11

(Keratinocytes) none


LAK cells rest
33.0
CCD1106
37.1




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
27.7
Liver cirrhosis
3.5


LAK cells IL-2 + IL-12
25.5
Lupus kidney
1.0


LAK cells IL-2 + IFN
35.6
NCI-H292 none
16.2


gamma


LAK cells IL-2 + IL-18
21.9
NCI-H292 IL-4
23.5


LAK cells
3.6
NCI-H292 IL-9
29.5


PMA/ionomycin


NK Cells IL-2 rest
15.1
NCI-H292 IL-13
13.4


Two Way MLR 3 day
9.4
NCI-H292 IFN gamma
20.6


Two Way MLR 5 day
17.4
HPAEC none
17.4


Two Way MLR 7 day
13.1
HPAEC TNF alpha + IL-
20.9




1beta


PBMC rest
0.8
Lung fibroblast none
37.9


PBMC PWM
88.9
Lung fibroblast TNF
34.9




alpha + IL-1beta


PBMC PHA-L
52.5
Lung fibroblast IL-4
69.7


Ramos (B cell) none
17.2
Lung fibroblast IL-9
49.7


Ramos (B cell)
31.9
Lung fibroblast IL-13
45.4


ionomycin


B lymphocytes PWM
75.8
Lung fibroblast IFN
90.8




gamma


B lymphocytes CD40L
9.9
Dermal fibroblast
54.3


and IL-4

CCD1070 rest


EOL-1 dbcAMP
11.0
Dermal fibroblast
84.1




CCD1070 TNF alpha


EOL-1 dbcAMP
8.1
Dermal fibroblast
30.6


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
38.2
Dermal fibroblast IFN
31.4




gamma


Dendritic cells LPS
31.9
Dermal fibroblast IL-4
45.4


Dendritic cells anti-
37.1
IBD Colitis 2
2.5


CD40


Monocytes rest
0.4
IBD Crohn's
4.7


Monocytes LPS
0.6
Colon
45.4


Macrophages rest
12.6
Lung
16.6


Macrophages LPS
5.8
Thymus
100.0


HUVEC none
16.0
Kidney
20.6


HUVEC starved
27.4










[1867]

927





TABLE BUD










Panel 5 Islet











Rel. Exp. (%)

Rel. Exp. (%)



Ag3424, Run

Ag3424, Run


Tissue Name
242385366
Tissue Name
242385366













97457_Patient-
8.2
94709_Donor 2 AM - A_adipose
6.7


02go_adipose


97476_Patient-
3.9
94710_Donor 2 AM - B_adipose
8.7


07sk_skeletal muscle


97477_Patient-
7.4
94711_Donor 2 AM - C_adipose
5.9


07ut_uterus


97478_Patient-
7.9
94712_Donor 2 AD - A -
8.3


07pl_placenta

adipose


99167_Bayer Patient
4.8
94713_Donor 2 AD - B_adipose
5.4


1


97482_Patient-
4.1
94714_Donor 2 AD - C_adipose
7.7


08ut_uterus


97483_Patient-
2.4
94742_Donor 3 U -
3.0


08pl_placenta

A_Mesenchymal Stem Cells


97486_Patient-
0.0
94743_Donor 3 U -
9.9


09sk_skeletal muscle

B_Mesenchymal Stem Cells


97487_Patient-
5.3
94730_Donor 3 AM - A_adipose
22.5


09ut_uterus


97488_Patient-
2.3
94731_Donor 3 AM - B_adipose
15.1


09pl_placenta


97492_Patient-
4.8
94732_Donor 3 AM - C_adipose
10.2


10ut_uterus


97493_Patient-
6.6
94733_Donor 3 AD - A_adipose
29.7


10pl_placenta


97495_Patient-
0.9
94734_Donor 3 AD - B_adipose
6.4


11go_adipose


97496_Patient-
0.3
94735_Donor 3 AD - C_adipose
34.9


11sk_skeletal muscle


97497_Patient-
9.8
77138_Liver_HepG2untreated
57.8


11ut_uterus


97498_Patient-
3.0
73556_Heart_Cardiac stromal
10.3


11pl_placenta

cells (primary)


97500_Patient-
1.7
81735_Small Intestine
23.7


12go_adipose


97501_Patient-
1.4
72409_Kidney_Proximal
4.5


12sk_skeletal muscle

Convoluted Tubule


97502_Patient-
10.2
82685_Small
1.2


12ut_uterus

intestine_Duodenum


97503_Patient-
3.2
90650_Adrenal_Adrenocortical
1.4


12pl_placenta

adenoma


94721_Donor 2 U -
6.8
72410_Kidney_HRCE
100.0


A_Mesenchymal


Stem Cells


94722_Donor 2 U -
2.8
72411_Kidney_HRE
69.7


B_Mesenchymal


Stem Cells


94723_Donor 2 U -
5.1
73139_Uterus_Uterine smooth
22.4


C_Mesenchymal

muscle cells


Stem Cells










[1868] CNS_neurodegeneration_v1.0 Summary: Ag3424 This panel confirms the expression of the CG59561-01 gene at low levels in the brain in an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. This expression profile suggests that this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[1869] General_screening_panel_v1.4 Summary: Ag3424 Results from one experiment with the CG59561-01 gene are not included. The amp plot indicates that there were experimental difficulties with this run. (Data not shown.)


[1870] Panel 4D Summary: Ag3424 The CG59561-01 gene encodes a protein homologous to cytosolic acyl coenzyme A thioester hydrolase (Brain acyl-CoA hydrolase, BACH). Among the tissue samples used in this panel, highest expression of this gene is detected in thymus (CT=29.6). In addition, expression of this gene is stimulated in activated primary and secondary—Th1, Th2 and Tr1 cells. Therefore, this gene product may play an important role in T cell development. Thus, therapeutics designed with the protein encoded for by this transcript could be important in regulating T cell function and treating T cell mediated diseases such as emphysema, asthma, arthritis, psoriasis, IBD, and systemic lupus erythematosus.


[1871] Interestingly, expression of this gene is also seen in activated PBMCs (CTs=30) as compared to resting PBMCs (CT=36) suggesting a role for this gene product in B-cell and T-cell proliferation. Therefore, small molecules that antagonize the function of this gene product may be useful as therapeutic drugs to reduce or eliminate the symptoms in patients with autoimmune and inflammatory diseases in which B cells play a part in the initiation or progression of the disease process, such as systemic lupus erythematosus, Crohn's disease, ulcerative colitis, multiple sclerosis, chronic obstructive pulmonary disease, asthma, emphysema, rheumatoid arthritis, or psoriasis.


[1872] Panel 5 Islet Summary: Ag3424 The CG59561-01 gene is expressed at low levels in adipose and placenta, with highest expression in the kidney (CT=30.8). As an enzyme involved in lipid homeostasis, therapeutic modulation of this gene product may be a treatment for obesity and obesity-related diseases, including Type 2 diabetes.


[1873] BV. CG59452-01: Cell Proliferation Related Protein Cap


[1874] Expression of gene CG59452-01 was assessed using the primer-probe set Ag3443, described in Table BVA. Results of the RTQ-PCR runs are shown in Tables BVB and BVC.
928TABLE BVAProbe Name Ag3443StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-caggaatgtatccaggacttca-3′22387623ProbeTET-5′-catctacaacaagcctggagatgaca-3′-TAMRA26431624Reverse5′-tttccagagcttctgccatt-3′20464625


[1875]

929





TABLE BVB










CNS_neurodegeneration_v1.0











Rel. Exp.

Rel. Exp.



(%) Ag3443,

(%) Ag3443,



Run

Run


Tissue Name
210374885
Tissue Name
210374885













AD 1 Hippo
10.2
Control (Path) 3
6.2




Temporal Ctx


AD 2 Hippo
28.3
Control (Path) 4
27.0




Temporal Ctx


AD 3 Hippo
8.0
AD 1 Occipital Ctx
13.6


AD 4 Hippo
4.8
AD 2 Occipital Ctx
0.0




(Missing)


AD 5 Hippo
84.1
AD 3 Occipital Ctx
6.0


AD 6 Hippo
71.7
AD 4 Occipital Ctx
17.9


Control 2 Hippo
31.4
AD 5 Occipital Ctx
54.3


Control 4 Hippo
6.1
AD 6 Occipital Ctx
22.7


Control (Path) 3
3.3
Control 1 Occipital
4.0


Hippo

Ctx


AD 1 Temporal
21.9
Control 2 Occipital
73.7


Ctx

Ctx


AD 2 Temporal
33.4
Control 3 Occipital
13.7


Ctx

Ctx


AD 3 Temporal
7.4
Control 4 Occipital
7.7


Ctx

Ctx


AD 4 Temporal
16.8
Control (Path) 1
100.0


Ctx

Occipital Ctx


AD 5 Inf Temporal
74.7
Control (Path) 2
11.0


Ctx

Occipital Ctx


AD 5 Sup
36.1
Control (Path) 3
1.3


Temporal Ctx

Occipital Ctx


AD 6 Inf Temporal
79.0
Control (Path) 4
15.3


Ctx

Occipital Ctx


AD 6 Sup
85.9
Control 1 Parietal
6.1


Temporal Ctx

Ctx


Control 1
8.6
Control 2 Parietal
35.8


Temporal Ctx

Ctx


Control 2
48.3
Control 3 Parietal
12.9


Temporal Ctx

Ctx


Control 3
11.4
Control (Path) 1
59.5


Temporal Ctx

Parietal Ctx


Control 3
6.5
Control (Path) 2
25.5


Temporal Ctx

Parietal Ctx


Control (Path) 1
93.3
Control (Path) 3
2.4


Temporal Ctx

Parietal Ctx


Control (Path) 2
23.8
Control (Path) 4
23.2


Temporal Ctx

Parietal Ctx










[1876]

930





TABLE BVC










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3443, Run

Ag3443, Run


Tissue Name
166397102
Tissue Name
166397102













Secondary Th1 act
22.7
HUVEC IL-1beta
18.2


Secondary Th2 act
25.7
HUVEC IFN gamma
18.6


Secondary Tr1 act
37.9
HUVEC TNF alpha +
16.6




IFN gamma


Secondary Th1 rest
15.7
HUVEC TNF alpha +
17.0




IL4


Secondary Th2 rest
11.2
HUVEC IL-11
9.3


Secondary Tr1 rest
11.5
Lung Microvascular EC
14.2




none


Primary Th1 act
16.6
Lung Microvascular EC
12.9




TNF alpha + IL-1beta


Primary Th2 act
29.9
Microvascular Dermal
17.7




EC none


Primary Tr1 act
44.1
Microsvasular Dermal
17.1




EC TNF alpha + IL-1beta


Primary Th1 rest
69.7
Bronchial epithelium
6.8




TNF alpha + IL-1beta


Primary Th2 rest
40.9
Small airway epithelium
8.5




none


Primary Tr1 rest
24.5
Small airway epithelium
40.9




TNF alpha + IL-1beta


CD45RA CD4
15.6
Coronery artery SMC rest
9.4


lymphocyte act


CD45RO CD4
30.4
Coronery artery SMC
8.5


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
19.3
Astrocytes rest
16.3


Secondary CD8
27.7
Astrocytes TNF alpha +
30.4


lymphocyte rest

IL-1beta


Secondary CD8
16.3
KU-812 (Basophil) rest
26.8


lymphocyte act


CD4 lymphocyte none
12.4
KU-812 (Basophil)
80.7




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
17.3
CCD1106
13.6


CD95 CH11

(Keratinocytes) none


LAK cells rest
10.7
CCD1106
100.0




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
30.4
Liver cirrhosis
10.4


LAK cells IL-2 + IL-12
24.5
Lupus kidney
16.5


LAK cells IL-2 + IFN
34.2
NCI-H292 none
22.4


gamma


LAK cells IL-2 + IL-18
20.9
NCI-H292 IL-4
36.9


LAK cells
13.3
NCI-H292 IL-9
27.5


PMA/ionomycin


NK Cells IL-2 rest
15.6
NCI-H292 IL-13
15.9


Two Way MLR 3 day
19.5
NCI-H292 IFN gamma
15.9


Two Way MLR 5 day
16.2
HPAEC none
9.3


Two Way MLR 7 day
15.1
HPAEC TNF alpha + IL-
18.9




1beta


PBMC rest
13.1
Lung fibroblast none
20.4


PBMC PWM
26.6
Lung fibroblast TNF
20.9




alpha + IL-1beta


PBMC PHA-L
9.6
Lung fibroblast IL-4
19.5


Ramos (B cell) none
39.2
Lung fibroblast IL-9
12.2


Ramos (B cell)
37.9
Lung fibroblast IL-13
10.5


ionomycin


B lymphocytes PWM
31.4
Lung fibroblast IFN
29.1




gamma


B lymphocytes CD40L
32.3
Dermal fibroblast
26.8


and IL-4

CCD1070 rest


EOL-1 dbcAMP
18.7
Dermal fibroblast
46.3




CCD1070 TNF alpha


EOL-1 dbcAMP
45.7
Dermal fibroblast
16.0


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
12.8
Dermal fibroblast IFN
7.5




gamma


Dendritic cells LPS
9.6
Dermal fibroblast IL-4
17.1


Dendritic cells anti-
14.6
IBD Colitis 2
4.2


CD40


Monocytes rest
20.6
IBD Crohn's
2.9


Monocytes LPS
20.9
Colon
49.0


Macrophages rest
15.8
Lung
11.1


Macrophages LPS
12.9
Thymus
20.2


HUVEC none
24.3
Kidney
33.2


HUVEC starved
33.7










[1877] CNS_neurodegeneration_v1.0 Summary: Ag3443 This panel confirms the expression of the CG59452-01 gene at significant levels in the brain in an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Expression of this gene in the brain suggests that it may play a role in central nervous system disorders other than Alzheimer's disease, such as Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[1878] General_screening_panel_v1.4 Summary: Ag3443 The amp plot indicates that there were experimental difficulties with this run. (Data not shown).


[1879] Panel 4D Summary: Ag3443 Highest expression of the CG59452-01 gene is detected in TNFalpha+IL-1 beta treated keratinocytes and PMA/ionomycin treated KU-812 basophil cells (CTs=24.5). Thus, antibody or small molecule therapies designed with the protein encoded for by this gene could block or inhibit inflammation or tissue damage due to basophil activation in response to asthma, allergies, hypersensitivity reactions, psoriasis, and viral infections.


[1880] BW. CG59572-01 and CG59572-02: Pseudouridine Synthase 3


[1881] Expression of gene CG59572-01 and CG59572-02 was assessed using the primer-probe set Ag3476, described in Table BWA. Results of the RTQ-PCR runs are shown in Tables BWB, BWC and BWD. Please note that CG59572-02 represents a full-length physical clone of the CG59572-01 gene, validating the prediction of the gene sequence.
931TABLE BWAProbe Name Ag3476StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-acctacaacaactgtgggctaa-3′221070626ProbeTET-5′-tcatgctgtcaaaactcacatgttgt-3′-TAMRA261092627Reverse5′-ggaacagtgtccagtccttgta-3′221127628


[1882]

932





TABLE BWB










CNS_neurodegeneration_v1.0











Rel. Exp.





(%) Ag3476,

Rel. Exp. (%)



Run

Ag3476, Run


Tissue Name
210377171
Tissue Name
210377171













AD 1 Hippo
16.7
Control (Path) 3
4.5




Temporal Ctx


AD 2 Hippo
23.8
Control (Path) 4
31.6




Temporal Ctx


AD 3 Hippo
10.3
AD 1 Occipital
28.5




Ctx


AD 4 Hippo
8.5
AD 2 Occipital
0.0




Ctx (Missing)


AD 5 hippo
88.3
AD 3 Occipital
7.9




Ctx


AD 6 Hippo
77.4
AD 4 Occipital
20.6




Ctx


Control 2 Hippo
37.4
AD 5 Occipital
35.4




Ctx


Control 4 Hippo
9.6
AD 6 Occipital
54.7




Ctx


Control (Path) 3
8.4
Control 1 Occipital
4.7


Hippo

Ctx


AD 1 Temporal Ctx
18.6
Control 2 Occipital
67.8




Ctx


AD 2 Temporal Ctx
32.3
Control 3 Occipital
15.6




Ctx


AD 3 Temporal Ctx
8.0
Control 4 Occipital
5.6




Ctx


AD 4 Temporal Ctx
21.6
Control (Path) 1
100.0




Occipital Ctx


AD 5 Inf Temporal
84.1
Control (Path) 2
7.8


Ctx

Occipital Ctx


AD 5 SupTemporal
41.5
Control (Path) 3
5.9


Ctx

Occipital Ctx


AD 6 Inf Temporal
77.4
Control (Path) 4
18.0


Ctx

Occipital Ctx


AD 6 Sup Temporal
88.3
Control 1 Parietal
8.1


Ctx

Ctx


Control 1 Temporal
5.4
Control 2 Parietal
47.0


Ctx

Ctx


Control 2 Temporal
40.1
Control 3 Parietal
18.2


Ctx

Ctx


Control 3 Temporal
22.1
Control (Path) 1
71.7


Ctx

Parietal Ctx


Control 4 Temporal
5.1
Control (Path) 2
20.6


Ctx

Parietal Ctx


Control (Path) 1
55.1
Control (Path) 3
5.3


Temporal Ctx

Parietal Ctx


Control (Path) 2
31.6
Control (Path) 4
46.3


Temporal Ctx

Parietal Ctx










[1883]

933





TABLE BWC










General_screening_panel_v1.4











Rel. Exp.

Rel. Exp.



(%) Ag3476,

(%) Ag3476,



Run

Run


Tissue Name
217119004
Tissue Name
217119004













Adipose
5.7
Renal ca. TK-10
13.9


Melanoma*
13.4
Bladder
16.3


Hs688(A).T


Melanoma*
14.6
Gastric ca. (liver met.)
42.9


Hs688(B).T

NCI-N87


Melanoma* M14
18.6
Gastric ca. KATO III
92.0


Melanoma*
38.7
Colon ca. SW-948
7.3


LOXIMVI


Melanoma* SK-
27.0
Colon ca. SW480
40.9


MEL-5


Squamous cell
9.9
Colon ca.* (SW480
27.5


carcinoma SCC-4

met) SW620


Testis Pool
5.9
Colon ca. HT29
24.0


Prostate ca.* (bone
34.4
Colon ca. HCT-116
32.5


met) PC-3


Prostate Pool
5.6
Colon ca. CaCo-2
52.1


Placenta
1.1
Colon cancer tissue
10.4


Uterus Pool
3.8
Colon ca. SW1116
3.9


Ovarian ca.
15.4
Colon ca. Colo-205
6.1


OVCAR-3


Ovarian ca. SK-
20.7
Colon ca. SW-48
9.0


OV-3


Ovarian ca.
14.5
Colon Pool
13.6


OVCAR-4


Ovarian ca.
44.8
Small Intestine Pool
8.4


OVCAR-5


Ovarian ca.
18.4
Stomach Pool
7.0


IGROV-1


Ovarian ca.
10.3
Bone Marrow Pool
4.0


OVCAR-8


Ovary
7.0
Fetal Heart
6.3


Breast ca. MCF-7
16.8
Heart Pool
5.4


Breast ca. MDA-
31.0
Lymph Node Pool
14.5


MB-231


Breast ca. BT 549
51.1
Fetal Skeletal Muscle
4.2


Breast ca. T47D
100.0
Skeletal Muscle Pool
10.7


Breast ca. MDA-N
28.7
Spleen Pool
5.4


Breast Pool
11.0
Thymus Pool
8.2


Trachea
6.2
CNS cancer
11.9




(glio/astro) U87-MG


Lung
2.0
CNS cancer
44.1




(glio/astro) U-118-MG


Fetal Lung
15.5
CNS cancer
29.9




(neuro; met) SK-N-AS


Lung ca. NCI-N417
14.5
CNS cancer (astro)
13.6




SF-539


Lung ca. LX-1
31.0
CNS cancer (astro)
43.8




SNB-75


Lung ca. NCI-H146
9.3
CNS cancer (glio)
16.0




SNB-19


Lung ca. SHP-77
36.6
CNS cancer (glio) SF-
44.8




295


Lung ca. A549
14.4
Brain (Amygdala)
3.6




Pool


Lung ca. NCI-H526
21.6
Brain (cerebellum)
7.8


Lung ca. NCI-H23
23.0
Brain (fetal)
7.6


Lung ca. NCI-H460
13.9
Brain (Hippocampus)
4.5




Pool


Lung ca. HOP-62
14.9
Cerebral Cortex Pool
6.3


Lung ca. NCI-H522
38.7
Brain (Substantia
3.4




nigra) Pool


Liver
1.9
Brain (Thalamus) Pool
6.9


Fetal Liver
17.2
Brain (whole)
3.8


Liver ca. HepG2
18.4
Spinal Cord Pool
3.6


Kidney Pool
12.9
Adrenal Gland
3.8


Fetal Kidney
15.3
Pituitary gland Pool
3.2


Renal ca. 786-0
13.4
Salivary Gland
1.8


Renal ca. A498
7.1
Thyroid (female)
4.4


Renal ca. ACHN
10.4
Pancreatic ca.
27.7




CAPAN2


Renal ca. UO-31
22.1
Pancreas Pool
14.7










[1884]

934





TABLE BWD










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3476, Run

Ag3476, Run


Tissue Name
166420471
Tissue Name
166420471













Secondary Th1 act
31.4
HUVEC IL-1beta
27.5


Secondary Th2 act
30.6
HUVEC IFN gamma
23.7


Secondary Tr1 act
40.3
HUVEC TNF alpha +
15.4




IFN gamma


Secondary Th1 rest
11.6
HUVEC TNF alpha +
16.2




IL4


Secondary Th2 rest
9.3
HUVEC IL-11
13.4


Secondary Tr1 rest
9.2
Lung Microvascular EC
12.3




none


Primary Th1 act
23.5
Lung Microvascular EC
11.0




TNF alpha + IL-1beta


Primary Th2 act
44.8
Microvascular Dermal
20.3




EC none


Primary Tr1 act
55.5
Microsvasular Dermal
13.6




EC TNF alpha + IL-1beta


Primary Th1 rest
48.6
Bronchial epithelium
7.8




TNF alpha + IL1beta


Primary Th2 rest
24.7
Small airway epithelium
9.5




none


Primary Tr1 rest
22.8
Small airway epithelium
48.0




TNF alpha + IL-1beta


CD45RA CD4
15.9
Coronery artery SMC rest
14.1


lymphocyte act


CD45RO CD4
45.1
Coronery artery SMC
9.8


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
26.2
Astrocytes rest
13.9


Secondary CD8
46.3
Astrocytes TNF alpha +
14.2


lymphocyte rest

IL-1beta


Secondary CD8
23.0
KU-812 (Basophil) rest
29.5


lymphocyte act


CD4 lymphocyte none
6.3
KU-812 (Basophil)
55.1




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
15.8
CCD1106
18.7


CD95 CH11

(Keratinocytes) none


LAK cells rest
8.4
CCD1106
100.0




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
29.1
Liver cirrhosis
12.8


LAK cells IL-2 + IL-12
35.8
Lupus kidney
7.9


LAK cells IL-2 + IFN
42.6
NCI-H292 none
44.4


gamma


LAK cells IL-2 + IL-18
28.7
NCI-H292 IL-4
52.5


LAK cells
14.0
NCI-H292 IL-9
55.5


PMA/ionomycin


NK Cells IL-2 rest
19.9
NCI-H292 IL-13
29.3


Two Way MLR 3 day
23.0
NCI-H292 IFN gamma
30.1


Two Way MLR 5 day
31.0
HPAEC none
10.7


Two Way MLR 7 day
18.0
HPAEC TNF alpha + IL-
13.1




1beta


PBMC rest
4.8
Lung fibroblast none
23.3


PBMC PWM
39.5
Lung fibroblast TNF
16.0




alpha + IL-1beta


PBMC PHA-L
11.4
Lung fibroblast IL-4
27.7


Ramos (B cell) none
18.2
Lung fibroblast IL-9
22.5


Ramos (B cell)
16.2
Lung fibroblast IL-13
19.6


ionomycin


B lymphocytes PWM
56.3
Lung fibroblast IFN
48.3




gamma


B lymphocytes CD40L
36.9
Dermal fibroblast
28.5


and IL-4

CCD1070 rest


EOL-1 dbcAMP
23.5
Dermal fibroblast
38.7




CCD1070 TNF alpha


EOL-1 dbcAMP
20.0
Dermal fibroblast
11.8


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
10.1
Dermal fibroblast IFN
9.9




gamma


Dendritic cells LPS
9.7
Dermal fibroblast IL-4
15.7


Dendritic cells anti-
10.2
IBD Colitis 2
6.6


CD40


Monocytes rest
12.0
IBD Crohn's
6.2


Monocytes LPS
12.5
Colon
46.0


Macrophages rest
13.3
Lung
12.6


Macrophages LPS
7.4
Thymus
21.8


HUVEC none
24.3
Kidney
18.3


HUVEC starved
33.4










[1885] CNS_neurodegeneration_v1.0 Summary: Ag3476 This panel confirms the expression of the CG59572-01 gene at low levels in the brain in an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.


[1886] General_screening_panel_v1.4 Summary: Ag3476 Highest expression of the CG59572-01 gene is detected in a breast cancer cell line sample (CT=27.4). Furthermore, moderate to high expression of this gene is detected in CNS cancer, colon cancer, gastric cancer, pancreatic cancer, lung cancer, ovarian cancer, and prostate cancer. Therefore, therapeutic modulation of the activity of this gene or its protein product, through the use of small molecule drugs, protein therapeutics or antibodies, might be beneficial in the treatment of these cancers.


[1887] This gene is expressed at low to moderate levels throughout the CNS, including in amygdala, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[1888] Among tissues with metabolic function, this gene is expressed at moderate to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.


[1889] In addition, this gene is expressed at much higher levels in fetal lung and liver tissue (CTs=30) when compared to expression in the adult counterpart (CTs=33). Thus, expression of this gene may be used to differentiate between the fetal and adult source of these tissues.


[1890] Panel 4D Summary: Ag3476 Highest expression of the CG59572-01 gene is detected in TNFalpha+IL-1 beta treated keratinocytes (CT=27.2). Expression of this gene appears to be stimulated in activated secondary Th1, Th2 and Tr1 cells, PWM treated PBMCs, PWM treated 13-lymphocytes, IL-2/IL-2+IL-12/IL-2+IFN gamma/IL-2+IL-18 treated LAK cells, and TNFalpha+IL-1beta treated small airway epithelium (CTs=28-30). Thus, this gene may be important in the activation of T and B cells or the function of activated T and B cells. Therefore, small molecules that antagonize the function of this gene product may reduce or eliminate the symptoms in patients with autoimmune and inflammatory diseases in which B and T cells play a part in the initiation or progression of the disease process, such as systemic lupus erythematosus, Crohn's disease, ulcerative colitis, multiple sclerosis, chronic obstructive pulmonary disease, asthma, emphysema, rheumatoid arthritis, or psoriasis.


[1891] BX. CG59522-01: Myosin I


[1892] Expression of gene CG59522-01 was assessed using the primer-probe set Ag3456, described in Table BXA. Results of the RTQ-PCR runs are shown in Table BXB.
935TABLE BXAProbe Name 3456StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-atgaactgcacttggagagaaa-3′22664629ProbeTET-5′-aatttcacacaccagggagcaggact-3′-TAMRA26699630Reverse5′-ctctgctcatcactcacagtca-3′22730631


[1893]

936





TABLE BXB










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3456, Run

Ag3456, Run


Tissue Name
166397214
Tissue Name
166397214













Secondary Th1 act
20.2
HUVEC IL-1beta
0.0


Secondary Th2 act
19.6
HUVEC IFN gamma
0.0


Secondary Tr1 act
35.4
HUVEC TNF alpha +
0.0




IFN gamma


Secondary Th1 rest
34.2
HUVEC TNF alpha +
0.0




IL4


Secondary Th2 rest
17.3
HUVEC IL-11
0.0


Secondary Tr1 rest
20.7
Lung Microvascular EC
0.0




none


Primary Th1 act
10.6
Lung Microvascular EC
0.0




TNF alpha + IL-1beta


Primary Th2 act
13.3
Microvascular Dermal
0.0




EC none


Primary Tr1 act
25.2
Microsvasular Dermal
0.0




EC TNF alpha + IL-1beta


Primary Th1 rest
100.0
Bronchial epithelium
0.0




TNF alpha + IL1beta


Primary Th2 rest
35.1
Small airway epithelium
0.0




none


Primary Tr1 rest
25.9
Small airway epithelium
0.0




TNF alpha + IL-1beta


CD45RA CD4
9.9
Coronery artery SMC rest
0.0


lymphocyte act


CD45RO CD4
28.9
Coronery artery SMC
0.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
27.5
Astrocytes rest
0.0


Secondary CD8
15.6
Astrocytes TNF alpha +
0.0


lymphocyte rest

IL-1beta


Secondary CD8
26.6
KU-812 (Basophil) rest
2.2


lymphocyte act


CD4 lymphocyte none
5.0
KU-812 (Basophil)
5.2




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
31.2
CCD1106
0.0


CD95 CH11

(Keratinocytes) none


LAK cells rest
4.7
CCD1106
1.0




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
41.5
Liver cirrhosis
0.8


LAK cells IL-2 + IL-12
22.4
Lupus kidney
0.4


LAK cells IL-2 + IFN
29.5
NCI-H292 none
0.3


gamma


LAK cells IL-2 + IL-18
25.7
NCI-H292 IL-4
0.1


LAK cells
4.4
NCI-H292 IL-9
0.0


PMA/ionomycin


NK Cells IL-2 rest
22.2
NCI-H292 IL-13
0.0


Two Way MLR 3 day
14.2
NCI-H292 IFN gamma
0.0


Two Way MLR 5 day
16.0
HPAEC none
0.0


Two Way MLR 7 day
17.2
HPAEC TNF alpha + IL-
0.0




1beta


PBMC rest
7.5
Lung fibroblast none
0.0


PBMC PWM
33.9
Lung fibroblast TNF
0.0




alpha + IL-1beta


PBMC PHA-L
12.7
Lung fibroblast IL-4
0.0


Ramos (B cell) none
4.7
Lung fibroblast IL-9
0.0


Ramos (B cell)
8.5
Lung fibroblast IL-13
0.1


ionomycin


B lymphocytes PWM
25.5
Lung fibroblast IFN
0.0




gamma


B lymphocytes CD40L
18.8
Dermal fibroblast
0.0


and IL-4

CCD1070 rest


EOL-1 dbcAMP
17.3
Dermal fibroblast
43.5




CCD1070 TNF alpha


EOL-1 dbcAMP
9.9
Dermal fibroblast
0.0


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
2.1
Dermal fibroblast IFN
0.0




gamma


Dendritic cells LPS
16.4
Dermal fibroblast IL-4
0.0


Dendritic cells anti-
1.6
IBD Colitis 2
0.3


CD40


Monocytes rest
20.9
IBD Crohn's
0.1


Monocytes LPS
45.7
Colon
4.2


Macrophages rest
1.3
Lung
2.5


Macrophages LPS
16.3
Thymus
0.0


HUVEC none
0.0
Kidney
11.3


HUVEC starved
0.0










[1894] CNS_neurodegeneration_v1.0 Summary: Ag3456 Expression of CG59522-01 gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1895] General_screening_panel_v1.4 Summary: Ag3456 Expression of CG59522-01 gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1896] Panel 4D Summary: Ag3456 Highest expression of the CG59522-01 gene is detected in sample derived from resting primary Th1 cells (CT=29.8). Thus, expression of this gene can be used to distinguish this sample from other samples in this panel. This gene is also expressed at low but significant levels in T cells prepared under a number of conditions, LAK cells, macrophages and dendritic cells also express the transcript. The only non-hematopoietic cell type that expresses the transcript detected by this primer and probe at significant levels is dermal fibroblasts. Colon and kidney also express low levels of the transcript. Thus, this transcript or the protein it encodes could be used to detect hematopoietically-derived cells. Furthermore, therapeutics designed with the protein encoded by this transcript could be important in the regulation the function of antigen presenting cells (macrophages and dendritic cells) or T cells and be important in the treatment of asthma, emphysema, psoriasis, arthritis, and IBD. Therefore, therapeutics designed with the protein encoded for by this transcript could be important in regulating T cell function and treating T and B cell mediated diseases such as asthma, arthritis, psoriasis, IBD, and systemic lupus erythematosus.


[1897] BY. CG59520-01: Farnesyl Pyrophosphate Synthetase


[1898] Expression of gene CG59520-01 was assessed using the primer-probe set Ag5923, described in Table BYA. Results of the RTQ-PCR runs are shown in Tables BYB and BYC.
937TABLE BYAProbe Name Ag5923StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-gaatgggaaaccagaaatcag-3′215632ProbeTET-5′-tttatgcccaagcaaagcaggatttc-3′-TAMRA2629633Reverse5′-accctaacgatctgggagtagt-3′2262634


[1899]

938





TABLE BYB










General_screening panel v1.5











Rel. Exp.

Rel. Exp.



(%) Ag5923,

(%) Ag5923,



Run

Run


Tissue Name
247608956
Tissue Name
247608956













Adipose
0.6
Renal ca. TK-10
12.1


Melanoma*
1.9
Bladder
7.1


Hs688(A).T


Melanoma*
2.9
Gastric ca. (liver met.)
26.2


Hs688(B).T

NCI-N87


Melanoma* M14
8.9
Gastric ca. KATO III
31.0


Melanoma*
3.9
Colon ca. SW-948
6.8


LOXIMVI


Melanoma* SK-
2.4
Colon ca. SW480
15.3


MEL-5


Squamous cell
1.8
Colon ca.* (SW480
8.2


carcinoma SCC-4

met) SW620


Testis Pool
15.1
Colon ca. HT29
1.9


Prostate ca.* (bone
5.6
Colon ca. HCT-116
9.3


met) PC-3


Prostate Pool
2.3
Colon ca. CaCo-2
6.4


Placenta
2.3
Colon cancer tissue
7.3


Uterus Pool
0.0
Colon ca. SW1116
7.1


Ovarian ca.
6.7
Colon ca. Colo-205
9.5


OVCAR-3


Ovarian ca. SK-
14.8
Colon ca. SW-48
3.8


OV-3


Ovarian ca.
4.2
Colon Pool
5.6


OVCAR-4


Ovarian ca.
23.0
Small Intestine Pool
7.0


OVCAR-5


Ovarian ca.
4.1
Stomach Pool
0.6


IGROV-1


Ovarian ca.
0.7
Bone Marrow Pool
2.1


OVCAR-8


Ovary
12.1
Fetal Heart
4.1


Breast ca. MCF-7
4.4
Heart Pool
1.1


Breast ca. MDA-
6.8
Lymph Node Pool
7.3


MB-231


Breast ca. BT 549
17.8
Fetal Skeletal Muscle
1.0


Breast ca. T47D
5.6
Skeletal Muscle Pool
5.3


Breast ca. MDA-N
2.5
Spleen Pool
2.0


Breast Pool
9.5
Thymus Pool
8.0


Trachea
14.1
CNS cancer
1.7




(glio/astro) U87-MG


Lung
13.9
CNS cancer
10.2




(glio/astro) U-118-MG


Fetal Lung
16.7
CNS cancer
2.8




(neuro; met) SK-N-AS


Lung ca. NCI-N417
1.7
CNS cancer (astro)
2.8




SF-539


Lung ca. LX-1
12.8
CNS cancer (astro)
14.2




SNB-75


Lung ca. NCI-H146
1.6
CNS cancer (glio)
3.9




SNB-19


Lung ca. SHP-77
1.5
CNS cancer (glio) SF-
10.8




295


Lung ca. A549
11.0
Brain (Amygdala)
1.8




Pool


Lung ca. NCI-H526
0.5
Brain (cerebellum)
4.0


Lung ca. NCI-H23
10.9
Brain (fetal)
4.6


Lung ca. NCI-H460
4.1
Brain (Hippocampus)
3.3




Pool


Lung ca. HOP-62
2.3
Cerebral Cortex Pool
0.0


Lung ca. NCI-H522
5.2
Brain (Substantia
3.2




nigra) Pool


Liver
0.5
Brain (Thalamus) Pool
1.6


Fetal Liver
4.3
Brain (whole)
1.8


Liver ca. HepG2
0.3
Spinal Cord Pool
1.7


Kidney Pool
13.6
Adrenal Gland
1.7


Fetal Kidney
7.1
Pituitary gland Pool
0.0


Renal ca. 786-0
11.7
Salivary Gland
1.2


Renal ca. A498
5.6
Thyroid (female)
0.5


Renal ca. ACHN
6.2
Pancreatic ca.
100.0




CAPAN2


Renal ca. UO-31
14.0
Pancreas Pool
15.3










[1900]

939





TABLE BYC










Panel 4.1D











Rel. Exp. (%)

Rel. Exp. (%)



Ag5923, Run

Ag5923, Run


Tissue Name
247579946
Tissue Name
247579946













Secondary Th1 act
14.6
HUVEC IL-1beta
5.3


Secondary Th2 act
36.6
HUVEC IFN gamma
12.1


Secondary Tr1 act
5.6
HUVEC TNF alpha +
0.0




IFN gamma


Secondary Th1 rest
0.0
HUVEC TNF alpha +
0.0




IL4


Secondary Th2 rest
10.5
HUVEC IL-11
6.7


Secondary Tr1 rest
0.0
Lung Microvascular EC
15.5




none


Primary Th1 act
0.0
Lung Microvascular EC
2.4




TNF alpha + IL-1beta


Primary Th2 act
11.1
Microvascular Dermal
0.0




EC none


Primary Tr1 act
11.0
Microsvasular Dermal
5.0




EC TNF alpha + IL-1beta


Primary Th1 rest
0.0
Bronchial epithelium
13.5




TNF alpha + IL1beta


Primary Th2 rest
1.5
Small airway epithelium
7.2




none


Primary Tr1 rest
1.3
Small airway epithelium
44.8




TNF alpha + IL-1beta


CD45RA CD4
13.5
Coronery artery SMC rest
1.6


lymphocyte act


CD45RO CD4
12.9
Coronery artery SMC
6.7


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
1.8
Astrocytes rest
1.5


Secondary CD8
3.6
Astrocytes TNF alpha +
0.0


lymphocyte rest

IL-1beta


Secondary CD8
0.0
KU-812 (Basophil) rest
0.0


lymphocyte act


CD4 lymphocyte none
0.0
KU-812 (Basophil)
15.3




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
0.0
CCD1106
21.5


CD95 CH11

(Keratinocytes) none


LAK cells rest
15.9
CCD1106
31.9




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
3.5
Liver cirrhosis
4.0


LAK cells IL-2 + IL-12
0.0
NCI-H292 none
61.1


LAK cells IL-2 + IFN
2.3
NCI-H292 IL-4
100.0


gamma


LAK cells IL-2 + IL-18
0.0
NCI-H292 IL-9
45.1


LAK cells
13.0
NCI-H292 IL-13
47.0


PMA/ionomycin


NK Cells IL-2 rest
37.1
NCI-H292 IFN gamma
14.5


Two Way MLR 3 day
4.9
HAPEC none
0.0


Two Way MLR 5 day
0.0
HPAEC TNF alpha + IL-
24.1




1beta


Two Way MLR 7 day
1.2
Lung fibroblast none
6.0


PBMC rest
0.0
Lung fibroblast TNF
3.7




alpha + IL-1beta


PBMC PWM
0.0
Lung fibroblast IL-4
1.0


PBMC PHA-L
0.0
Lung fibroblast IL-9
8.7


Ramos (B cell) none
0.0
Lung fibroblast IL-13
0.0


Ramos (B cell)
17.7
Lung fibroblast IFN
3.8


ionomycin

gamma


B lymphocytes PWM
11.4
Dermal fibroblast
5.8




CCD1070 rest


B lymphocytes CD40L
23.2
Dermal fibroblast
21.3


and IL-4

CCD1070 TNF alpha


EOL-1 dbcAMP
21.0
Dermal fibroblast
8.6




CCD1070 IL-1beta


EOL-1 dbcAMP
3.5
Dermal fibroblast IFN
12.9


PMA/ionomycin

gamma


Dendritic cells none
11.7
Dermal fibroblast IL-4
13.8


Dendritic cells LPS
8.4
Dermal Fibroblasts rest
0.0


Dendritic cells anti-
3.8
Neutrophils TNFa + LPS
1.5


CD40


Monocytes rest
0.0
Neutrophils rest
18.0


Monocytes LPS
57.8
Colon
0.0


Macrophages rest
1.7
Lung
0.0


Macrophages LPS
9.8
Thymus
8.8


HUVEC none
3.1
Kidney
4.0


HUVEC starved
2.5










[1901] CNS_neurodegeneration_v1.0 Summary: Ag5923 Expression of the CG59520-01 gene is low/undetectable (CTs>34.5) across all of the samples on this panel (data not shown).


[1902] General_screening_panel_v1.5 Summary: Ag5923 Highest expression of the CG59520-01 gene is detected in sample derived from a pancreatic cancer cell line (CT=31.5). Thus, expression of this gene can be used in distinguishing this sample from other samples from the panel and as a marker for pancreatic cancer. In addition low levels of expression of this gene are associated with samples derived from CNS, colon, gastric, renal, lung, breast, ovarian and melanoma cnacer cell lines. This gene encodes a farnesyl pyrophosphate synthetase, which is involved in cholesterol biosynthesis. It has been suggested that in several types of cancer, activation of p21 would be aided by continuous farnesylation due to stimulation of the cholesterol biosynthetic pathway in tumors (Rao, 1995). Therefore, therapeutic modulation of the activity of protein encoded by this gene may be beneficial in the treatment of these cancers.


[1903] In addition, low but significant levels of expression in the pancreas suggest that this gene product may be useful in the treatment of type II diabetes.



REFERENCES

[1904] 1. Rao K N. (1995) The significance of the cholesterol biosynthetic pathway in cell growth and carcinogenesis (review). Anticancer Res March-April 1995;15(2):309-14


[1905] Panel 4.1D Summary: Ag5923 High expression of the CG59520-01 gene is detected in sample derived from untreated and IL4 treated NCI-H292 cells (CTs=33). Thus, expression of this gene could be used to distinguish these samples from other samples from the panel. Also, therapeutic modulation of the activity of this gene product may be beneficial in the treatment asthma and emphysema.


[1906] Panel 5 Islet Summary: Ag5923 Expression of the CG59520-01 gene is low/undetectable (CTs>34.5) across all of the samples on this panel (data not shown).


[1907] BZ. CG-59704-01: Serine/Threonine Kinase


[1908] Expression of gene CG59704-01 was assessed using the primer-probe set Ag3509, described in Table BZA. Results of the RTQ-PCR runs are shown in Tables BZB, BZC and BZD.
940TALE BZAProbe Name Ag3509StartPrimersSequencesLengthPositionSEQ ID NO:Forward5′-gacttccctcacctagcttctg-3′224228635ProbeTET-5′-actgcatgccaccactgctgagta-3′-TAMRA244257636Reverse5′-caccaacctagcaaacaaacag-3′224281637


[1909]

941





TABLE BZB










CNS_neurodegeneration_v1.0













Rel. Exp.



Rel. Exp. (%)

(%) Ag3509,



Ag3509, Run

Run


Tissue Name
210499481
Tissue Name
210499481













AD 1 Hippo
20.2
Control (Path) 3
24.1




Temporal Ctx


AD 2 Hippo
20.2
Control (Path) 4
20.7




Temporal Ctx


AD 3 Hippo
23.3
AD 1 Occipital Ctx
16.4


AD 4 Hippo
13.5
AD 2 Occipital Ctx
0.0




(Missing)


AD 5 Hippo
66.4
AD 3 Occipital Ctx
9.9


AD 6 Hippo
84.7
AD 4 Occipital Ctx
4.6


Control 2 Hippo
18.0
AD 5 Occipital Ctx
30.4


Control 4 Hippo
0.4
AD 6 Occipital Ctx
0.0


Control (Path) 3
0.3
Control 1 Occipital
10.0


Hippo

Ctx


AD 1 Temporal
23.7
Control 2 Occipital
35.6


Ctx

Ctx


AD 2 Temporal
15.4
Control 3 Occipital
16.3


Ctx

Ctx


AD 3 Temporal
10.8
Control 4 Occipital
25.2


Ctx

Ctx


AD 4 Temporal
18.8
Control (Path) 1
57.4


Ctx

Occipital Ctx


AD 5 Inf Temporal
100.0
Control (Path) 2
8.1


Ctx

Occipital Ctx


AD 5 Sup
72.2
Control (Path) 3
5.4


Temporal Ctx

Occipital Ctx


AD 6 Inf Temporal
21.9
Control (Path) 4
30.4


Ctx

Occipital Ctx


AD 6 Sup
62.4
Control 1 Parietal
12.1


Temporal Ctx

Ctx


Control 1
5.4
Control 2 Parietal
54.0


Temporal Ctx

Ctx


Control 2
30.6
Control 3 Parietal
12.0


Temporal Ctx

Ctx


Control 3
6.0
Control (Path) 1
51.4


Temporal Ctx

Parietal Ctx


Control 3
12.2
Control (Path) 2
16.0


Temporal Ctx

Parietal Ctx


Control (Path) 1
40.9
Control (Path) 3
2.1


Temporal Ctx

Parietal Ctx


Control (Path) 2
31.9
Control (Path) 4
29.7


Temporal Ctx

Parietal Ctx










[1910]

942





TABLE BZC










General_screening_panel_v1.4











Rel. Exp.

Rel. Exp.



(%) Ag3509,

(%) Ag3509,



Run

Run


Tissue Name
217240617
Tissue Name
217240617













Adipose
9.5
Renal ca. TK-10
20.4


Melanoma*
8.7
Bladder
16.6


Hs688(A).T


Melanoma*
4.5
Gastric ca. (liver met.)
37.6


Hs688(B).T

NCI-N87


Melanoma* M14
12.0
Gastric ca. KATO III
23.3


Melanoma*
3.1
Colon ca. SW-948
6.9


LOXIMVI


Melanoma* SK-
11.0
Colon ca. SW480
35.8


MEL-5


Squamous cell
9.5
Colon ca.* (SW480
24.7


carcinoma SCC-4

met) SW620


Testis Pool
5.4
Colon ca. HT29
9.3


Prostate ca.* (bone
24.1
Colon ca. HCT-116
62.4


met) PC-3


Prostate Pool
4.5
Colon ca. CaCo-2
8.8


Placenta
1.9
Colon cancer tissue
10.9


Uterus Pool
1.8
Colon ca. SW1116
3.7


Ovarian ca.
43.2
Colon ca. Colo-205
1.2


OVCAR-3


Ovarian ca. SK-
42.3
Colon ca. SW-48
2.8


OV-3


Ovarian ca.
1.1
Colon Pool
9.2


OVCAR-4


Ovarian ca.
19.1
Small Intestine Pool
8.2


OVCAR-5


Ovarian ca.
8.7
Stomach Pool
3.7


IGROV-1


Ovarian ca.
7.5
Bone Marrow Pool
4.6


OVCAR-8


Ovary
3.4
Fetal Heart
7.3


Breast ca. MCF-7
20.7
Heart Pool
5.6


Breast ca. MDA-
32.8
Lymph Node Pool
10.1


MB-231


Breast ca. BT 549
35.1
Fetal Skeletal Muscle
6.7


Breast ca. T47D
34.4
Skeletal Muscle Pool
3.6


Breast ca. MDA-N
18.6
Spleen Pool
7.7


Breast Pool
15.7
Thymus Pool
11.0


Trachea
6.8
CNS cancer
27.4




(glio/astro) U87-MG


Lung
15.3
CNS cancer
45.4




(glio/astro) U-118-MG


Fetal Lung
17.6
CNS cancer
16.3




(neuro; met) SK-N-AS


Lung ca. NCI-N417
11.8
CNS cancer (astro)
9.9




SF-539


Lung ca. LX-1
29.5
CNS cancer (astro)
50.7




SNB-75


Lung ca. NCI-H146
5.6
CNS cancer (glio)
7.0




SNB-19


Lung ca. SHP-77
19.1
CNS cancer (glio) SF-
25.7




295


Lung ca. A549
17.2
Brain (Amygdala)
4.9




Pool


Lung ca. NCI-H526
4.2
Brain (cerebellum)
13.7


Lung ca. NCI-H23
100.0
Brain (fetal)
14.8


Lung ca. NCI-H460
27.2
Brain (Hippocampus)
3.7




Pool


Lung ca. HOP-62
16.2
Cerebral Cortex Pool
3.0


Lung ca. NCI-H522
29.9
Brain (Substantia
1.7




nigra) Pool


Liver
0.0
Brain (Thalamus) Pool
5.6


Fetal Liver
10.1
Brain (whole)
6.1


Liver ca. HepG2
17.7
Spinal Cord Pool
2.0


Kidney Pool
26.1
Adrenal Gland
8.8


Fetal Kidney
24.3
Pituitary gland Pool
3.4


Renal ca. 786-0
19.8
Salivary Gland
4.9


Renal ca. A498
2.4
Thyroid (female)
3.4


Renal ca. ACHN
8.2
Pancreatic ca.
34.2




CAPAN2


Renal ca. UO-31
9.5
Pancreas Pool
16.7










[1911]

943





TABLE BZD










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3509, Run

Ag3509, Run


Tissue Name
166407201
Tissue Name
166407201













Secondary Th1 act
50.0
HUVEC IL-1beta
4.7


Secondary Th2 act
45.4
HUVEC IFN gamma
4.8


Secondary Tr1 act
87.7
HUVEC TNF alpha +
10.0




IFN gamma


Secondary Th1 rest
17.4
HUVEC TNF alpha +
19.9




IL4


Secondary Th2 rest
21.9
HUVEC IL-11
13.4


Secondary Tr1 rest
32.5
Lung Microvascular EC
14.1




none


Primary Th1 act
40.9
Lung Microvascular EC
24.8




TNF alpha + IL-1beta


Primary Th2 act
83.5
Microvascular Dermal
22.1




EC none


Primary Tr1 act
100.0
Microsvasular Dermal
12.2




EC TNF alpha + IL-1beta


Primary Th1 rest
75.8
Bronchial epithelium
9.9




TNF alpha + IL1beta


Primary Th2 rest
31.0
Small airway epithelium
7.7




none


Primary Tr1 rest
41.5
Small airway epithelium
23.0




TNF alpha + IL-1beta


CD45RA CD4
21.9
Coronery artery SMC rest
7.6


lymphocyte act


CD45RO CD4
56.6
Coronery artery SMC
2.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
58.6
Astrocytes rest
25.5


Secondary CD8
51.4
Astrocytes TNF alpha +
28.5


lymphocyte rest

IL-1beta


Secondary CD8
52.1
KU-812 (Basophil) rest
25.5


lymphocyte act


CD4 lymphocyte none
21.0
KU-812 (Basophil)
68.8




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
41.8
CCD1106
17.4


CD95 CH11

(Keratinocytes) none


LAK cells rest
27.9
CCD1106
36.6




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
58.6
Liver cirrhosis
57.8


LAK cells IL-2 + IL-12
61.1
Lupus kidney
24.3


LAK cells IL-2 + IFN
85.3
NCI-H292 none
20.0


gamma


LAK cells IL-2 + IL-18
61.1
NCI-H292 IL-4
21.6


LAK cells
49.3
NCI-H292 IL-9
24.5


PMA/ionomycin


NK Cells IL-2 rest
43.2
NCI-H292 IL-13
24.8


Two Way MLR 3 day
50.0
NCI-H292 IFN gamma
14.8


Two Way MLR 5 day
39.5
HPAEC none
9.5


Two Way MLR 7 day
37.1
HPAEC TNF alpha + IL-
25.9




1beta


PBMC rest
15.1
Lung fibroblast none
19.6


PBMC PWM
44.8
Lung fibroblast TNF
21.3




alpha + IL-1beta


PBMC PHA-L
14.8
Lung fibroblast IL-4
18.8


Ramos (B cell) none
75.3
Lung fibroblast IL-9
17.8


Ramos (B cell)
17.8
Lung fibroblast IL-13
21.9


ionomycin


B lymphocytes PWM
33.4
Lung fibroblast IFN
21.3




gamma


B lymphocytes CD40L
42.3
Dermal fibroblast
46.7


and IL-4

CCD1070 rest


EOL-1 dbcAMP
25.3
Dermal fibroblast
69.3




CCD1070 TNF alpha


EOL-1 dbcAMP
18.9
Dermal fibroblast
20.3


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
10.7
Dermal fibroblast IFN
17.4




gamma


Dendritic cells LPS
13.6
Dermal fibroblast IL-4
21.8


Dendritic cells anti-
12.2
IBD Colitis 2
7.1


CD40


Monocytes rest
10.0
IBD Crohn's
5.5


Monocytes LPS
25.3
Colon
53.6


Macrophages rest
29.3
Lung
5.6


Macrophages LPS
7.2
Thymus
27.5


HUVEC none
24.1
Kidney
51.4


HUVEC starved
33.9










[1912] CNS_neurodegeneration_v1.0 Summary: Ag3509 This panel confirms the expression of this gene at low levels in the brain in an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment.


[1913] General_screening_panel_v1.4 Summary: Ag3509 Highest expression of the CG59704-01 gene is detected in a sample derived from a lung cancer cell line (CT=31.69). Thus, expression of this gene can be used in distinguishing this sample from other samples in this panel. Furthermore, moderate expression of this gene is associated with cell lines derived from pancreatic, brain, colon, gastric, renal, lung, breast and ovarian cancers. Therefore, therapeutic modulation of the activity of this gene or its protein product, through the use of small molecule drugs, or antibodies, might be beneficial in the treatment of these cancers.


[1914] Panel 4D Summary: Ag3509 Expression of the CG59704-01 gene is stimulated in T cells, LAK cells and B cells, with highest expression in primary activated Tr1 cells (CT=32). Therefore, therapeutics designed with the protein encoded for by this transcript could be important in regulating T and B cell function and treating T cell/B cell mediated diseases such as asthma, arthritis, psoriasis, IBD, allergies, hypersensitivity reactions, microbial and viral infections systemic lupus erythematosus, multiple sclerosis, chronic obstructive pulmonary disease and systemic lupus erythematosus.


[1915] Furthermore, expression of this gene is decreased in colon samples from patients with IBD colitis and Crohn's disease relative to normal colon. Therefore, therapeutic modulation of the activity of this gene product may be useful in the treatment of inflammatory bowel disease.


[1916] Panel 5 Islet Summary: Ag3509 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[1917] CA. CG59628-01: Short-Chain Dehydrogenase Like Homo Sapiens


[1918] Expression of gene CG59628-01 was assessed using the primer-probe set Ag3500, described in Table CAA. Results of the RTQ-PCR runs are shown in Tables CAB and CAC.
944TABLE CCAProbe Name Ag3500StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-gcagatgtggtgatgagtatga-3′221159638ProbeTET-5′-tcaggtaaactaaaaccaacaatggca-3′-TAMRA271207639Reverse5′-atcttcaatttccctgacatga-3′221235640


[1919]

945





TABLE CAB










General_screening_panel_v1.4











Rel. Exp.

Rel. Exp.



(%) Ag3500,

(%) Ag3500,



Run

Run


Tissue Name
217131378
Tissue Name
217131378













Adipose
25.0
Renal ca. TK-10
82.4


Melanoma*
19.3
Bladder
15.6


Hs688(A).T


Melanoma*
18.3
Gastric ca. (liver met.)
36.3


Hs688(B).T

NCI-N87


Melanoma* M14
33.9
Gastric ca. KATO III
51.1


Melanoma*
36.3
Colon ca. SW-948
17.8


LOXIMVI


Melanoma* SK-
61.1
Colon ca. SW480
66.4


MEL-5


Squamous cell
17.0
Colon ca.* (SW480
36.1


carcinoma SCC-4

met) SW620


Testis Pool
11.4
Colon ca. HT29
31.6


Prostate ca.* (bone
35.1
Colon ca. HCT-116
46.0


met) PC-3


Prostate Pool
3.9
Colon ca. CaCo-2
58.6


Placenta
1.2
Colon cancer tissue
24.1


Uterus Pool
1.9
Colon ca. SW1116
6.7


Ovarian ca.
12.2
Colon ca. Colo-205
12.1


OVCAR-3


Ovarian ca. SK-
55.9
Colon ca. SW-48
25.0


OV-3


Ovarian ca.
7.2
Colon Pool
16.2


OVCAR-4


Ovarian ca.
47.6
Small Intestine Pool
9.9


OVCAR-5


Ovarian ca.
23.8
Stomach Pool
6.2


IGROV-1


Ovarian ca.
16.5
Bone Marrow Pool
4.6


OVCAR-8


Ovary
31.2
Fetal Heart
27.0


Breast ca. MCF-7
9.7
Heart Pool
12.9


Breast ca. MDA-
33.2
Lymph Node Pool
13.1


MB-231


Breast ca. BT 549
42.0
Fetal Skeletal Muscle
13.7


Breast ca. T47D
90.8
Skeletal Muscle Pool
40.9


Breast ca. MDA-N
18.9
Spleen Pool
11.6


Breast Pool
14.1
Thymus Pool
13.4


Trachea
7.7
CNS cancer
27.0




(glio/astro) U87-MG


Lung
8.1
CNS cancer
39.0




(glio/astro) U-118-MG


Fetal Lung
27.7
CNS cancer
20.0




(neuro; met) SK-N-AS


Lung ca. NCI-N417
4.4
CNS cancer (astro)
15.0




SF-539


Lung ca. LX-1
30.1
CNS cancer (astro)
100.0




SNB-75


Lung ca. NCI-H146
1.7
CNS cancer (glio)
22.5




SNB-19


Lung ca. SHP-77
27.4
CNS cancer (glio) SF-
20.6




295


Lung ca. A549
24.5
Brain (Amygdala)
4.5




Pool


Lung ca. NCI-H526
5.6
Brain (cerebellum)
1.8


Lung ca. NCI-H23
23.8
Brain (fetal)
2.0


Lung ca. NCI-H460
22.2
Brain (Hippocampus)
9.2




Pool


Lung ca. HOP-62
14.4
Cerebral Cortex Pool
11.7


Lung ca. NCI-H522
24.0
Brain (Substantia
7.7




nigra) Pool


Liver
1.2
Brain (Thalamus) Pool
10.1


Fetal Liver
28.7
Brain (whole)
2.8


Liver ca. HepG2
36.6
Spinal Cord Pool
17.2


Kidney Pool
10.8
Adrenal Gland
18.6


Fetal Kidney
13.6
Pituitary gland Pool
2.4


Renal ca. 786-0
44.1
Salivary Gland
1.7


Renal ca. A498
13.7
Thyroid (female)
11.3


Renal ca. ACHN
19.1
Pancreatic ca.
34.9




CAPAN2


Renal ca. UO-31
37.4
Pancreas Pool
22.8










[1920]

946





TABLE CAC










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3500, Run

Ag3500, Run


Tissue Name
166441942
Tissue Name
166441942













Secondary Th1 act
6.0
HUVEC IL-1beta
6.8


Secondary Th2 act
10.1
HUVEC IFN gamma
17.1


Secondary Tr1 act
14.0
HUVEC TNF alpha +
5.6




IFN gamma


Secondary Th1 rest
4.1
HUVEC TNF alpha +
6.2




IL4


Secondary Th2 rest
2.4
HUVEC IL-11
7.2


Secondary Tr1 rest
3.1
Lung Microvascular EC
6.0




none


Primary Th1 act
1.7
Lung Microvascular EC
4.5




TNF alpha + IL-1beta


Primary Th2 act
6.4
Microvascular Dermal
20.0




EC none


Primary Tr1 act
10.5
Microsvasular Dermal
5.9




EC TNF alpha + IL-1beta


Primary Th1 rest
20.3
Bronchial epithelium
6.8




TNF alpha + IL1beta


Primary Th2 rest
9.8
Small airway epithelium
11.2




none


Primary Tr1 rest
18.0
Small airway epithelium
50.7




TNF alpha + IL-1beta


CD45RA CD4
11.5
Coronery artery SMC rest
6.8


lymphocyte act


CD45RO CD4
8.5
Coronery artery SMC
5.7


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
13.2
Astrocytes rest
17.9


Secondary CD8
6.9
Astrocytes TNF alpha +
26.2


lymphocyte rest

IL-1beta


Secondary CD8
6.2
KU-812 (Basophil) rest
13.2


lymphocyte act


CD4 lymphocyte none
2.1
KU-812 (Basophil)
23.0




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
3.2
CCD1106
14.5


CD95 CH11

(Keratinocytes) none


LAK cells rest
2.5
CCD1106
68.8




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
12.2
Liver cirrhosis
20.4


LAK cells IL-2 + IL-12
9.8
Lupus kidney
13.5


LAK cells IL-2 + IFN
11.7
NCI-H292 none
47.0


gamma


LAK cells IL-2 + IL-18
8.0
NCI-H292 IL-4
21.8


LAK cells
2.0
NCI-H292 IL-9
29.5


PMA/ionomycin


NK Cells IL-2 rest
6.3
NCI-H292 IL-13
13.3


Two Way MLR 3 day
6.4
NCI-H292 IFN gamma
12.3


Two Way MLR 5 day
12.3
HPAEC none
10.5


Two Way MLR 7 day
6.3
HPAEC TNF alpha + IL-
7.3




1beta


PBMC rest
3.3
Lung fibroblast none
10.1


PBMC PWM
11.6
Lung fibroblast TNF
15.1




alpha + IL-1beta


PBMC PHA-L
5.7
Lung fibroblast IL-4
9.1


Ramos (B cell) none
6.1
Lung fibroblast IL-9
9.3


Ramos (B cell)
8.3
Lung fibroblast IL-13
8.1


ionomycin


B lymphocytes PWM
27.4
Lung fibroblast IFN
24.5




gamma


B lymphocytes CD40L
15.0
Dermal fibroblast
39.8


and IL-4

CCD1070 rest


EOL-1 dbcAMP
20.7
Dermal fibroblast
47.3




CCD1070 TNF alpha


EOL-1 dbcAMP
4.7
Dermal fibroblast
12.4


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
6.9
Dermal fibroblast IFN
11.4




gamma


Dendritic cells LPS
11.6
Dermal fibroblast IL-4
48.3


Dendritic cells anti-
3.8
IBD Colitis 2
2.2


CD40


Monocytes rest
6.0
IBD Crohn's
8.4


Monocytes LPS
2.3
Colon
100.0


Macrophages rest
12.2
Lung
14.0


Macrophages LPS
5.4
Thymus
73.2


HUVEC none
19.2
Kidney
25.0


HUVEC starved
31.9










[1921] CNS_neurodegeneration_v1.0 Summary: Ag3500 Results from one experiment with the CG59628-01 gene are not included. The amp plot indicates that there were experimental difficulties with this run.


[1922] General_screening_panel_v1.4 Summary: Ag3500 Highest expression of the CG59628-01 gene is detected in a sample derived from a CNS cancer cell line (CT=31.1). Therefore, expression of this gene may be used to distinguish this sample from the other samples on this panel. In addition, significant expression of this gene is associated with samples derived from colon, ovarian, breast, renal, lung, melanoma, and brain cancer cell lines. Therefore, therapeutic modulation of the activity of this gene or its protein product might be beneficial in the treatment of these cancers.


[1923] Among tissues with metabolic function, this gene is expressed at low but significant levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.


[1924] This molecule is also expressed at low levels in the CNS, including the hippocampus, thalamus, substantia nigra and cerebral cortex. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurologic disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.


[1925] Panel 4.1D Summary: Ag3500 Highest expression of the CG59628-01 gene is detected in colon (CT=30.3). Therefore, expression of this gene may be used to distinguish colon from the other tissues on this panel. Furthermore, expression of this gene is decreased in colon samples from patients with IBD colitis and Crohn's disease relative to normal colon. Therefore, therapeutic modulation of the activity of the GPCR encoded by this gene may be useful in the treatment of inflammatory bowel disease.


[1926] CB. CG59671-02: Acetyl-Coenzyme A Synthetase


[1927] Expression of gene CG59671-02 was assessed using the primer-probe sets Ag3506 and Ag3581, described in Tables CBA and CBB. Results of the RTQ-PCR runs are shown in Tables CBC, CBD, CBE and CBF.
947TABLE CBAProbe Name Ag3506SEQ IDPrimersSequencesLengthStart PositionNO:Forward5′-aggacacagctacgtggtgtat-3′221072641ProbeTET-5′-cctctctgcaatggtgccaccag-3′-TAMRA231097642Reverse5′-gataaactggggtgctctcaa-3′211128643


[1928]

948






TABLE CBB










Probe Name Ag3581
















Start
SEQ ID



Primers
Sequences
Length
Position
NO:





Forward
5′-aggacacagctacgtggtgtat-3′
22
1072
644






Probe
TET-5′-cctctctgcaatggtgccaccag-3′-TAMRA
23
1097
645





Reverse
5′-gataaactggggtgctctcaa-3′
21
1128
646t










[1929]

949





TABLE CBC










CNS_neurodegeneration_v1.0













Rel. Exp. (%)
Rel. Exp. (%)

Rel. Exp. (%)
Rel. Exp. (%)


Tissue
Ag3506, Run
Ag3581, Run
Tissue
Ag3506, Run
Ag3581, Run


Name
210497900
210643840
Name
210497900
210643840















AD 1 Hippo
30.1
36.9
Control
15.8
21.5





(Path) 3





Temporal





Ctx


AD 2 Hippo
87.7
89.5
Control
42.6
53.6





(Path) 4





Temporal





Ctx


AD 3 Hippo
12.5
12.5
AD 1
35.6
31.4





Occipital





Ctx


AD 4 Hippo
29.1
38.4
AD 2
0.0
0.0





Occipital





Ctx





(Missing)


AD 5 Hippo
55.5
69.3
AD 3
17.8
18.7





Occipital





Ctx


AD 6 Hippo
24.1
33.4
AD 4
47.0
38.4





Occipital





Ctx


Control 2
42.3
56.3
AD 5
42.9
26.1


Hippo


Occipital





Ctx


Control 4
42.6
60.3
AD 6
24.3
51.1


Hippo


Occipital





Ctx


Control
19.8
23.0
Control 1
20.3
16.2


(Path) 3


Occipital


Hippo


Ctx


AD 1
63.7
48.3
Control 2
71.2
63.7


Temporal


Occipital


Ctx


Ctx


AD 2
60.7
87.7
Control 3
35.4
41.5


Temporal


Occipital


Ctx


Ctx


AD 3
15.9
15.6
Control 4
20.0
27.9


Temporal


Occipital


Ctx


Ctx


AD 4
47.0
57.0
Control
81.2
100.0


Temporal


(Path) 1


Ctx


Occipital





Ctx


AD 5 Inf
68.3
72.2
Control
18.9
26.4


Temporal


(Path) 2


Ctx


Occipital





Ctx


AD 5 Sup
65.5
57.8
Control
15.7
10.1


Temporal


(Path) 3


Ctx


Occipital





Ctx


AD 6 Inf
29.5
35.6
Control
24.8
26.8


Temporal


(Path) 4


Ctx


Occipital





Ctx


AD 6 Sup
31.2
31.9
Control 1
21.9
33.7


Temporal


Parietal Ctx


Ctx


Control 1
22.5
29.3
Control 2
51.8
79.0


Temporal


Parietal Ctx


Ctx


Control 2
55.1
58.6
Control 3
31.4
38.4


Temporal


Parietal Ctx


Ctx


Control 3
26.4
34.6
Control
100.0
93.3


Temporal


(Path) 1


Ctx


Parietal Ctx


Control 3
35.6
35.8
Control
51.1
57.4


Temporal


(Path) 2


Ctx


Parietal Ctx


Control
62.9
73.7
Control
17.1
17.2


(Path) 1


(Path) 3


Temporal


Parietal Ctx


Ctx


Control
54.0
55.1
Control
54.3
55.9


(Path) 2


(Path) 4


Temporal


Parietal Ctx


Ctx










[1930]

950





TABLE CBD










General_screening_panel_v1.4













Rel. Exp. (%)
Rel. Exp. (%)

Rel. Exp. (%)
Rel. Exp. (%)



Ag3506, Run
Ag3581, Run

Ag3506, Run
Ag3581, Run


Tissue Name
217236187
217423588
Tissue Name
217236187
217423588















Adipose
3.6
3.5
Renal ca. TK-10
4.1
3.4


Melanoma*
1.8
1.0
Bladder
16.5
12.2


Hs688(A).T


Melanoma*
0.6
0.6
Gastric ca. (liver
21.5
17.3


Hs688(B).T


met.) NCI-N87


Melanoma*
100.0
30.4
Gastric ca.
63.3
53.2


M14


KATO III


Melanoma*
0.0
0.0
Colon ca. SW-
8.0
5.0


LOXIMVI


948


Melanoma*
7.5
100.0
Colon ca.
20.7
16.6


SK-MEL-5


SW480


Squamous
10.9
6.3
Colon ca.*
0.0
0.1


cell


(SW480 met)


carcinoma


SW620


SCC-4


Testis Pool
11.9
9.8
Colon ca. HT29
24.7
15.7


Prostate ca.*
2.0
2.3
Colon ca. HCT-
0.0
0.0


(bone met)


116


PC-3


Prostate Pool
13.0
7.5
Colon ca. CaCo-2
60.3
40.1


Placenta
87.1
50.3
Colon cancer
30.8
18.8





tissue


Uterus Pool
7.0
4.5
Colon ca.
5.3
2.4





SW1116


Ovarian ca.
28.5
14.4
Colon ca. Colo-
1.9
1.9


OVCAR-3


205


Ovarian ca.
7.7
4.2
Colon ca. SW-48
33.2
16.8


SK-OV-3


Ovarian ca.
2.6
1.0
Colon Pool
14.3
15.1


OVCAR-4


Ovarian ca.
28.3
14.1
Small Intestine
15.0
7.4


OVCAR-5


Pool


Ovarian ca.
0.5
0.2
Stomach Pool
8.3
4.8


IGROV-1


Ovarian ca.
1.4
1.1
Bone Marrow
7.3
4.7


OVCAR-8


Pool


Ovary
7.9
7.3
Fetal Heart
16.0
12.8


Breast ca.
3.8
2.1
Heart Pool
13.1
10.1


MCF-7


Breast ca.
8.2
6.0
Lymph Node
16.3
9.2


MDA-MB-


Pool


231


Breast ca. BT
1.6
1.2
Fetal Skeletal
6.9
3.7


549


Muscle


Breast ca.
62.9
31.2
Skeletal Muscle
18.9
15.1


T47D


Pool


Breast ca.
29.7
15.4
Spleen Pool
8.8
6.9


MDA-N


Breast Pool
12.5
8.8
Thymus Pool
19.6
11.6


Trachea
12.4
8.2
CNS cancer
0.6
0.3





(glio/astro) U87-





MG


Lung
1.7
0.8
CNS cancer
0.4
0.2





(glio/astro) U-





118-MG


Fetal Lung
29.7
18.0
CNS cancer
3.4
2.2





(neuro; met) SK-





N-AS


Lung ca.
0.1
0.0
CNS cancer
0.1
0.0


NCI-N417


(astro) SF-539


Lung ca. LX-1
0.1
0.1
CNS cancer
10.4
2.1





(astro) SNB-75


Lung ca.
0.3
0.1
CNS cancer
1.0
0.2


NCI-H146


(glio) SNB-19


Lung ca.
7.8
5.0
CNS cancer
1.3
0.6


SHP-77


(glio) SF-295


Lung ca.
7.8
5.1
Brain
10.3
5.9


A549


(Amygdala) Pool


Lung ca.
10.2
2.5
Brain
32.3
21.0


NCI-H526


(cerebellum)


Lung ca.
3.4
3.2
Brain (fetal)
9.7
4.7


NCI-H23


Lung ca.
1.9
0.8
Brain
15.5
10.6


NCI-H460


(Hippocampus)





Pool


Lung ca.
0.9
0.6
Cerebral Cortex
20.7
14.5


HOP-62


Pool


Lung ca.
0.1
0.1
Brain (Substantia
18.8
9.9


NCI-H522


nigra) Pool


Liver
0.8
0.5
Brain
15.9
10.4





(Thalamus) Pool


Fetal Liver
37.1
22.4
Brain (whole)
20.3
14.3


Liver ca.
1.8
0.8
Spinal Cord Pool
14.8
9.0


HepG2


Kidney Pool
18.7
14.9
Adrenal Gland
5.6
3.8


Fetal Kidney
6.2
6.0
Pituitary gland
1.6
1.0





Pool


Renal ca.
0.3
0.1
Salivary Gland
15.3
8.6


786-0


Renal ca.
1.8
1.1
Thyroid (female)
11.0
11.4


A498


Renal ca.
4.3
1.4
Pancreatic ca.
0.3
0.2


ACHN


CAPAN2


Renal ca.
9.3
2.5
Pancreas Pool
16.7
16.5


UO-31










[1931]

951





TABLE CBE










Panel 4.1D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3581, Run

Ag3581, Run


Tissue Name
169910402
Tissue Name
169910402













Secondary Th1 act
36.6
HUVEC IL-1beta
4.0


Secondary Th2 act
38.2
HUVEC IFN gamma
19.5


Secondary Tr1 act
45.1
HUVEC TNF alpha +
5.3




IFN gamma


Secondary Th1 rest
72.2
HUVEC TNF alpha +
2.6




IL4


Secondary Th2 rest
58.2
HUVEC IL-11
11.5


Secondary Tr1 rest
79.0
Lung Microvascular EC
27.9




none


Primary Th1 act
23.2
Lung Microvascular EC
28.1




TNF alpha + IL-1beta


Primary Th2 act
48.6
Microvascular Dermal
7.9




EC none


Primary Tr1 act
38.4
Microsvasular Dermal
10.6




EC TNF alpha + IL-1beta


Primary Th1 rest
90.8
Bronchial epithelium
6.9




TNF alpha + IL1beta


Primary Th2 rest
99.3
Small airway epithelium
1.7




none


Primary Tr1 rest
90.8
Small airway epithelium
3.2




TNF alpha + IL-1beta


CD45RA CD4
15.2
Coronery artery SMC rest
0.3


lymphocyte act


CD45RO CD4
45.1
Coronery artery SMC
0.3


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
36.3
Astrocytes rest
0.0


Secondary CD8
27.0
Astrocytes TNF alpha +
0.0


lymphocyte rest

IL-1beta


Secondary CD8
41.2
KU-812 (Basophil) rest
100.0


lymphocyte act


CD4 lymphocyte none
31.0
KU-812 (Basophil)
25.2




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
77.4
CCD1106
13.0


CD95 CH11

(Keratinocytes) none


LAK cells rest
40.6
CCD1106
19.3




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
66.0
Liver cirrhosis
8.9


LAK cells IL-2 + IL-12
28.3
NCI-H292 none
0.5


LAK cells IL-2 + IFN
34.9
NCI-H292 IL-4
0.8


gamma


LAK cells IL-2 + IL-18
32.1
NCI-H292 IL-9
0.8


LAK cells
9.3
NCI-H292 IL-13
1.2


PMA/ionomycin


NK Cells IL-2 rest
82.4
NCI-H292 IFN gamma
3.0


Two Way MLR 3 day
59.9
HPAEC none
8.6


Two Way MLR 5 day
28.7
HPAEC TNF alpha + IL-
7.7




1beta


Two Way MLR 7 day
27.4
Lung fibroblast none
1.9


PBMC rest
45.1
Lung fibroblast TNF
0.1




alpha + IL-1beta


PBMC PWM
19.5
Lung fibroblast IL-4
1.2


PBMC PHA-L
28.1
Lung fibroblast IL-9
0.3


Ramos (B cell) none
47.0
Lung fibroblast IL-13
0.6


Ramos (B cell)
37.4
Lung fibroblast IFN
2.6


ionomycin

gamma


B lymphocytes PWM
16.4
Dermal fibroblast
3.6




CCD1070 rest


B lymphocytes CD40L
48.6
Dermal fibroblast
73.7


and IL-4

CCD1070 TNF alpha


EOL-1 dbcAMP
0.3
Dermal fibroblast
3.5




CCD1070 IL-1beta


EOL-1 dbcAMP
0.0
Dermal fibroblast IFN
8.3


PMA/ionomycin

gamma


Dendritic cells none
24.0
Dermal fibroblast IL-4
6.1


Dendritic cells LPS
6.5
Dermal Fibroblasts rest
23.0


Dendritic cells anti-
24.1
Neutrophils TNFa + LPS
2.1


CD40


Monocytes rest
44.8
Neutrophils rest
8.7


Monocytes LPS
10.7
Colon
69.3


Macrophages rest
38.7
Lung
27.7


Macrophages LPS
9.5
Thymus
75.3


HUVEC none
2.9
Kidney
84.7


HUVEC starved
3.3










[1932]

952





TABLE CBF










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3506, Run

Ag3506, Run


Tissue Name
166407188
Tissue Name
166407188













Secondary Th1 act
8.4
HUVEC IL-1beta
0.4


Secondary Th2 act
7.2
HUVEC IFN gamma
6.7


Secondary Tr1 act
11.4
HUVEC TNF alpha +
1.1




IFN gamma


Secondary Th1 rest
31.6
HUVEC TNF alpha +
1.0




IL4


Secondary Th2 rest
13.7
HUVEC IL-11
2.3


Secondary Tr1 rest
22.5
Lung Microvascular EC
3.8




none


Primary Th1 act
3.9
Lung Microvascular EC
4.0




TNF alpha + IL-1beta


Primary Th2 act
14.6
Microvascular Dermal
3.4




EC none


Primary Tr1 act
14.3
Microsvasular Dermal
2.8




EC TNF alpha + IL-1beta


Primary Th1 rest
69.7
Bronchial epithelium
0.9




TNF alpha + IL1beta


Primary Th2 rest
44.1
Small airway epithelium
0.2




none


Primary Tr1 rest
28.9
Small airway epithelium
1.2




TNF alpha + IL-1beta


CD45RA CD4
3.2
Coronery artery SMC rest
0.0


lymphocyte act


CD45RO CD4
12.3
Coronery artery SMC
0.3


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
8.7
Astrocytes rest
0.1


Secondary CD8
9.5
Astrocytes TNF alpha +
0.1


lymphocyte rest

IL-1beta


Secondary CD8
12.0
KU-812 (Basophil) rest
18.3


lymphocyte act


CD4 lymphocyte none
9.6
KU-812 (Basophil)
14.9




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
23.8
CCD1106
2.0


CD95 CH11

(Keratinocytes) none


LAK cells rest
6.8
CCD1106
11.7




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
21.2
Liver cirrhosis
5.4


LAK cells IL-2 + IL-12
8.5
Lupus kidney
12.2


LAK cells IL-2 + IFN
12.2
NCI-H292 none
0.2


gamma


LAK cells IL-2 + IL-18
12.0
NCI-H292 IL-4
0.2


LAK cells
1.8
NCI-H292 IL-9
0.2


PMA/ionomycin


NK Cells IL-2 rest
16.0
NCI-H292 IL-13
0.0


Two Way MLR 3 day
16.6
NCI-H292 IFN gamma
0.1


Two Way MLR 5 day
7.2
HPAEC none
2.9


Two Way MLR 7 day
9.6
HPAEC TNF alpha + IL-
2.8




1beta


PBMC rest
8.5
Lung fibroblast none
0.5


PBMC PWM
3.5
Lung fibroblast TNF
0.6




alpha + IL-1beta


PBMC PHA-L
2.8
Lung fibroblast IL-4
0.1


Ramos (B cell) none
11.3
Lung fibroblast IL-9
0.1


Ramos (B cell)
5.6
Lung fibroblast IL-13
0.0


ionomycin


B lymphocytes PWM
6.2
Lung fibroblast IFN
0.5




gamma


B lymphocytes CD40L
12.2
Dermal fibroblast
1.1


and IL-4

CCD1070 rest


EOL-1 dbcAMP
0.1
Dermal fibroblast
21.8




CCD1070 TNF alpha


EOL-1 dbcAMP
0.0
Dermal fibroblast
1.0


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
4.3
Dermal fibroblast IFN
2.1




gamma


Dendritic cells LPS
1.4
Dermal fibroblast IL-4
1.8


Dendritic cells anti-
4.6
IBD Colitis 2
2.6


CD40


Monocytes rest
11.9
IBD Crohn's
5.5


Monocytes LPS
1.7
Colon
100.0


Macrophages rest
9.3
Lung
5.9


Macrophages LPS
1.6
Thymus
37.9


HUVEC none
0.9
Kidney
24.7


HUVEC starved
1.7










[1933] CNS_neurodegeneration_v1.0 Summary: Ag3506/Ag3581 This panel confirms the expression of the CG59671-02 gene at significant levels in the brain in an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment.


[1934] This gene is expressed at moderate levels throughout the CNS, including in amygdala, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord as observed in panel 1.4. Therefore, this gene may play a role in other central nervous system disorders such as, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression


[1935] General_screening_panel_v1.4 Summary: Ag3506/Ag3581 Two experiments produce results that are in very good agreement. Highest expression of the CG59671-02 gene is observed in samples derived from melanoma cell lines (CTs=23-35). Thus, expression of this gene can be used in distinguishing these samples from other samples in the panel. In addition, significant levels of expression of this gene are also associated with colon cancer, ovarian cancer, breast cancer, and lung cancer cell lines. Therefore, therapeutic modulation of the activity of this gene or its protein product might be beneficial in the treatment of these cancers.


[1936] This gene is also expressed at low to moderate levels in a number of tissues with metabolic or endocrine function, including adipose, adrenal gland, gastrointestinal tract, pancreas, skeletal muscle and thyroid. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.


[1937] This gene is also expressed at high to moderate levels in all regions of the CNS examined. Please see Panel CNS_neurodegeneration_v1.0 for discussion of utility of this gene in the central nervous system.


[1938] Panel 4.1D Summary: Ag3581 Highest expression of the CG59671-02 gene is observed in the resting KU-812 sample (CT=29.18). In addition, high expression of this gene is detected in colon, lung, thymus and kidney. Therefore, therapies designed with the protein encoded for by this gene could be important in the treatment of inflammatory or autoimmune diseases that affect the kidney, lung and kidney including, asthma, allergies, lupus and glomerulonephritis. Expression of this gene is decreased in colon samples from patients with IBD colitis and Crohn's disease relative to normal colon. Therefore, therapeutic modulation of the activity of the protein encoded by this gene may also be useful in the treatment of inflammatory bowel disease.


[1939] Expression of this gene appears to be down-regulated in activated primary and secondary Th1, Th2, and Tr1 cells. Also, TNF alpha stimulates the expression of this gene in resting dermal fibroblasts. Therefore, therapeutics designed with the protein encoded by this transcript could be important in regulating T cell function and treating diseases such as asthma, arthritis, psoriasis, IBD, and systemic lupus erythematosus.


[1940] Panel 4D Summary: Ag3506 Highest expression of CG59671-02 is observed colon sample (CT=27.3). Overall, the expression pattern using this probe is in excellent agreement with results in panel 4.1 D for Ag3581. Please see that panel for discussion of utility of this gene in inflammation.


[1941] CC. CG56870-01: NDR3


[1942] Expression of gene CG56870-01 was assessed using the primer-probe set Ag2075, described in Table CCA. Results of the RTQ-PCR runs are shown in Tables CCB, CCC, CCD and CCE. Please note that CG56870-02 represents a full-length physical clone of the CG56870-01 gene, validating the prediction of the gene sequence.


[1943] Table CCA. Probe Name Ag2075
953TABLE CCAProbe Name Ag2075StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-catggatgaacttcaggatgtt-3′2270647ProbeTET-5′-cagctcacagagatcaaaccacttct-3′-TAMRA2692648Reverse5′-tgacagtcaaagtcctggaagt-3′22141649


[1944]

954





TABLE CCB










Panel 1.3D











Rel. Exp. (%)

Rel. Exp. (%)



Ag2075,

Ag2075,


Tissue Name
Run 152355202
Tissue Name
Run 152355202













Liver adenocarcinoma
11.9
Kidney (fetal)
1.4


Pancreas
0.8
Renal ca. 786-0
3.5


Pancreatic ca. CAPAN2
1.6
Renal ca. A498
12.9


Adrenal gland
2.4
Renal ca. RXF 393
1.5


Thyroid
1.8
Renal ca. ACHN
1.7


Salivary gland
1.2
Renal ca. UO-31
6.8


Pituitary gland
2.4
Renal ca. TK-10
2.8


Brain (fetal)
3.2
Liver
0.4


Brain (whole)
25.2
Liver (fetal)
0.8


Brain (amygdala)
14.1
Liver ca.
6.7




(hepatoblast) HepG2


Brain (cerebellum)
10.8
Lung
2.1


Brain (hippocampus)
39.8
Lung (fetal)
3.2


Brain (substantia nigra)
2.7
Lung ca. (small cell)
4.1




LX-1


Brain (thalamus)
12.4
Lung ca. (small cell)
3.8




NCI-H69


Cerebral Cortex
100.0
Lung ca. (s.cell var.)
3.8




SHP-77


Spinal cord
3.5
Lung ca. (large
0.6




cell)NCI-H460


glio/astro U87-MG
6.4
Lung ca. (non-sm.
3.0




cell) A549


glio/astro U-118-MG
10.4
Lung ca. (non-s.cell)
7.7




NCI-H23


astrocytoma SW1783
5.1
Lung ca. (non-s.cell)
3.1




HOP-62


neuro*; met SK-N-AS
6.2
Lung ca. (non-s.cl)
6.3




NCI-H522


astrocytoma SF-539
5.4
Lung ca. (squam.)
1.4




SW 900


astrocytoma SNB-75
6.7
Lung ca. (squam.)
1.4




NCI-H596


glioma SNB-19
3.1
Mammary gland
2.4


glioma U251
2.0
Breast ca.* (pl.ef)
1.8




MCF-7


glioma SF-295
3.4
Breast ca.* (pl.ef)
11.6




MDA-MB-231


Heart (fetal)
6.7
Breast ca.* (pl.ef)
9.0




T47D


Heart
1.4
Breast ca. BT-549
4.8


Skeletal muscle (fetal)
18.0
Breast ca. MDA-N
4.2


Skeletal muscle
0.7
Ovary
13.4


Bone marrow
0.9
Ovarian ca.
1.8




OVCAR-3


Thymus
0.9
Ovarian ca.
1.6




OVCAR-4


Spleen
3.7
Ovarian ca.
1.8




OVCAR-5


Lymph node
1.9
Ovarian ca.
4.9




OVCAR-8


Colorectal
3.3
Ovarian ca. IGROV-1
1.6


Stomach
2.7
Ovarian ca.*
5.8




(ascites) SK-OV-3


Small intestine
2.5
Uterus
2.4


Colon ca. SW480
10.4
Placenta
1.2


Colon ca.*
3.7
Prostate
6.0


SW620(SW480 met)


Colon ca. HT29
4.6
Prostate ca.* (bone
4.5




met)PC-3


Colon ca. HCT-116
3.6
Testis
1.7


Colon ca. CaCo-2
10.3
Melanoma
3.8




Hs688(A).T


Colon ca.
3.2
Melanoma* (met)
4.4


tissue(ODO3866)

Hs688(B).T


Colon ca. HCC-2998
2.6
Melanoma UACC-
1.4




62


Gastric ca.* (liver met)
3.1
Melanoma M14
1.8


NCI-N87


Bladder
0.8
Melanoma LOX
3.3




IMVI


Trachea
2.0
Melanoma* (met)
2.4




SK-MEL-5


Kidney
1.3
Adipose
1.2










[1945]

955





TABLE CCC










Panel 2.2











Rel. Exp.

Rel. Exp.



(%) Ag2075,

(%) Ag2075,



Run

Run


Tissue Name
174255357
Tissue Name
174255357













Normal Colon
27.7
Kidney Margin
46.3




(OD04348)


Colon cancer
52.9
Kidney malignant
19.2


(OD06064)

cancer (OD06204B)


Colon Margin
30.1
Kidney normal
14.3


(OD06064)

adjacent tissue




(OD06204E)


Colon cancer
5.5
Kidney Cancer
66.0


(OD06159)

(OD04450-01)


Colon Margin
21.0
Kidney Margin
19.8


(OD06159)

(OD04450-03)


Colon cancer
22.2
Kidney Cancer
3.0


(OD06297-04)

8120613


Colon Margin
41.8
Kidney Margin
11.0


(OD06297-05)

8120614


CC Gr.2 ascend colon
4.0
Kidney Cancer
6.8


(ODO3921)

9010320


CC Margin
6.7
Kidney Margin
9.7


(OD03921)

9010321


Colon cancer metastasis
11.1
Kidney Cancer
35.6


(OD06104)

8120607


Lung Margin
42.6
Kidney Margin
13.7


(OD06104)

8120608


Colon mets to lung
17.8
Normal Uterus
59.5


(OD04451-01)


Lung Margin
9.3
Uterine Cancer 064011
9.7


(OD04451-02)


Normal Prostate
51.4
Normal Thyroid
8.8


Prostate Cancer
23.0
Thyroid Cancer
11.2


(OD04410)

064010


Prostate Margin
19.3
Thyroid Cancer
17.9


(OD04410)

A302152


Normal Ovary
22.8
Thyroid Margin
5.5




A302153


Ovarian cancer
9.9
Normal Breast
33.2


(OD06283-03)


Ovarian Margin
17.1
Breast Cancer
8.5


(OD06283-07)

(OD04566)


Ovarian Cancer 064008
18.0
Breast Cancer 1024
36.1


Ovarian cancer
6.6
Breast Cancer
18.4


(OD06145)

(OD04590-01)


Ovarian Margin
12.5
Breast Cancer Mets
31.9


(OD06145)

(OD04590-03)


Ovarian cancer
14.7
Breast Cancer
45.4


(OD06455-03)

Metastasis (OD0465505)


Ovarian Margin
21.8
Breast Cancer 064006
11.5


(OD06455-07)


Normal Lung
21.9
Breast Cancer
20.9


Invasive poor diff. lung
17.6
9100266 Breast
35.1


adeno (OD04945-01)

Margin 9100265


Lung Margin
12.2
Breast Cancer
9.7


(ODO4945-03)

A209073


Lung Malignant Cancer
8.7
Breast Margin
22.2


(OD03126)

A2090734


Lung Margin
7.4
Breast cancer
100.0


(OD03126)

(OD06083)


Lung Cancer
9.9
Breast cancer node
63.7


(OD05014A)

metastasis (OD06083)


Lung Margin
21.8
Normal Liver
9.9


(OD05014B)


Lung cancer
5.1
Liver Cancer 1026
5.6


(OD06081)


Lung Margin
7.9
Liver Cancer 1025
13.5


(OD06081)


Lung Cancer
17.4
Liver Cancer 6004-T
4.8


(OD04237-01)


Lung Margin
24.0
Liver Tissue 6004-N
9.3


(OD04237-02)


Ocular Melanoma
9.7
Liver Cancer 6005-T
15.7


Metastasis


Ocular Melanoma
4.6
Liver Tissue 6005-N
20.4


Margin (Liver)


Melanoma Metastasis
19.8
Liver Cancer 064003
10.7


Melanoma Margin
21.6
Normal Bladder
8.0


(Lung)


Normal Kidney
11.0
Bladder Cancer 1023
10.5


Kidney Ca, Nuclear
37.6
Bladder Cancer
17.3


grade 2 (OD04338)

A302173


Kidney Margin
22.1
Normal Stomach
37.9


(OD04338)


Kidney Ca Nuclear
21.6
Gastric Cancer
11.1


grade 1/2 (OD04339)

9060397


Kidney Margin
12.9
Stomach Margin
20.6


(OD04339)

9060396


Kidney Ca, Clear
6.5
Gastric Cancer
22.7


cell type (OD04340)

9060395


Kidney Margin
18.4
Stomach Margin
36.1


(OD04340)

9060394


Kidney Ca, Nuclear
12.9
Gastric Cancer 064005
8.1


grade 3 (OD04348)










[1946]

956





TABLE CCD










Panel 3D











Rel. Exp. (%)

Rel. Exp. (%)



Ag2075, Run

Ag2075, Run


Tissue Name
164750734
Tissue Name
164750734













Daoy-Medulloblastoma
6.7
Ca Ski-Cervical epidermoid
50.3




carcinoma (metastasis)


TE671-
9.0
ES-2-Ovarian clear cell
13.9


Medulloblastoma

carcinoma


D283 Med-
35.4
Ramos-Stimulated with
2.7


Medulloblastoma

PMA/ionomycin 6 h


PFSK-1-Primitive
15.4
Ramos-Stimulated with
3.3


Neuroectodermal

PMA/ionomycin 14 h


XF-498-CNS
4.4
MEG-01-Chronic
3.4




myelogenous leukemia




(megokaryoblast)


SNB-78-Glioma
23.3
Raji-Burkitt's Lymphoma
3.7


SF-268-Glioblastoma
13.6
Daudi-Burkitt's lymphoma
6.5


T98G-Glioblastoma
18.6
U266-B-cell plasmacytoma
8.4


SK-N-SH-
17.0
CA46-Burkitt's lymphoma
7.2


Neuroblastoma


(metastasis)


SF-295-Glioblastoma
8.4
RL-non-Hodgkin's B-cell
3.5




lymphoma


Cerebellum
74.7
JM1-pre-B-cell lymphoma
3.1


Cerebellum
62.4
Jurkat-T cell leukemia
11.6


NCI-H292-
45.7
TF-1-Erythroleukemia
13.4


Mucoepidermoid lung


carcinoma


DMS-114-Small cell
10.9
HUT 78-T-cell lymphoma
10.0


lung cancer


DMS-79-Small cell
100.0
U937-Histiocytic lymphoma
18.2


lung cancer


NCI-H146-Small cell
30.6
KU-812-Myelogenous
6.0


lung cancer

leukemia


NCI-H526-Small cell
57.4
769-P-Clear cell renal
11.3


lung cancer

carcinoma


NCI-N417-Small cell
15.2
Caki-2-Clear cell renal
10.4


lung cancer

carcinoma


NCI-H82-Small cell
36.9
SW 839-Clear cell renal
2.2


lung cancer

carcinoma


NCI-H157-Squamous
51.1
G401-Wilms' tumor
6.2


cell lung cancer


(metastasis)


NCI-H1155-Large cell
26.6
Hs766T-Pancreatic
42.9


lung cancer

carcinoma (LN metastasis)


NCI-H1299-Large cell
44.4
CAPAN-1-Pancreatic
5.0


lung cancer

adenocarcinoma (liver




metastasis)


NCI-H727-Lung
47.0
SU86.86-Pancreatic
28.1


carcinoid

carcinoma (liver metastasis)


NCI-UMC-11-Lung
60.3
BxPC-3-Pancreatic
6.3


carcinoid

adenocarcinoma


LX-1-Small cell lung
23.5
HPAC-Pancreatic
7.4


cancer

adenocarcinoma


Colo-205-Colon cancer
29.5
MIA PaCa-2-Pancreatic
3.6




carcinoma


KM12-Colon cancer
24.0
CFPAC-1-Pancreatic ductal
40.9




adenocarcinoma


KM20L2-Colon cancer
8.4
PANC-1-Pancreatic
20.9




epithelioid ductal carcinoma


NCI-H716-Colon
23.3
T24-Bladder carcinma
13.1


cancer

(transitional cell)


SW-48-Colon
27.0
5637-Bladder carcinoma
11.0


adenocarcinoma


SW1116-Colon
10.0
HT-1197-Bladder
9.2


adenocarcinoma

carcinoma


LS 174T-Colon
9.9
UM-UC-3-Bladder
7.2


adenocarcinoma

carcinma (transitional cell)


SW-948-Colon
1.1
A204-Rhabdomyosarcoma
7.0


adenocarcinoma


SW-480-Colon
8.8
HT-1080-Fibrosarcoma
16.6


adenocarcinoma


NCI-SNU-5-Gastric
7.2
MG-63-Osteosarcoma
16.7


carcinoma


KATO III-Gastric
32.8
SK-LMS-1-
26.4


carcinoma

Leiomyosarcoma (vulva)


NCI-SNU-16-Gastric
13.6
SJRH30-
16.8


carcinoma

Rhabdomyosarcoma (met to




bone marrow)


NCI-SNU-1-Gastric
16.0
A431-Epidermoid
9.8


carcinoma

carcinoma


RF-1-Gastric
2.1
WM266-4-Melanoma
12.0


adenocarcinoma


RF-48-Gastric
4.0
DU 145-Prostate carcinoma
0.1


adenocarcinoma

(brain metastasis)


MKN-45-Gastric
28.7
MDA-MB-468-Breast
14.7


carcinoma

adenocarcinoma


NCI-N87-Gastric
13.3
SCC-4-Squamous cell
0.9


carcinoma

carcinoma of tongue


OVCAR-5-Ovarian
2.6
SCC-9-Squamous cell
0.3


carcinoma

carcinoma of tongue


RL95-2-Uterine
7.2
SCC-15-Squamous cell
0.5


carcinoma

carcinoma of tongue


HelaS3-Cervical
13.4
CAL 27-Squamous cell
21.2


adenocarcinoma

carcinoma of tongue










[1947]

957





TABLE CCE










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag2075, Run

Ag2075, Run


Tissue Name
152787491
Tissue Name
152787491













Secondary Th1 act
46.3
HUVEC IL-1beta
25.0


Secondary Th2 act
39.2
HUVEC IFN gamma
33.0


Secondary Tr1 act
31.9
HUVEC TNF alpha +
13.1




IFN gamma


Secondary Th1 rest
11.7
HUVEC TNF alpha +
20.7




IL4


Secondary Th2 rest
13.9
HUVEC IL-11
20.0


Secondary Tr1 rest
21.6
Lung Microvascular EC
22.7




none


Primary Th1 act
30.1
Lung Microvascular EC
15.0




TNF alpha + IL-1beta


Primary Th2 act
39.2
Microvascular Dermal
26.8




EC none


Primary Tr1 act
54.7
Microsvasular Dermal
16.6




EC TNF alpha + IL-1beta


Primary Th1 rest
84.1
Bronchial epithelium
4.9




TNF alpha + IL1beta


Primary Th2 rest
48.6
Small airway epithelium
19.9




none


Primary Tr1 rest
39.0
Small airway epithelium
72.7




TNF alpha + IL-1beta


CD45RA CD4
21.8
Coronery artery SMC rest
27.9


lymphocyte act


CD45RO CD4
33.0
Coronery artery SMC
19.6


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
25.5
Astrocytes rest
26.4


Secondary CD8
21.5
Astrocytes TNF alpha +
13.2


lymphocyte rest

IL-1beta


Secondary CD8
29.3
KU-812 (Basophil) rest
6.3


lymphocyte act


CD4 lymphocyte none
12.7
KU-812 (Basophil)
16.0




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
25.5
CCD1106
46.0


CD95 CH11

(Keratinocytes) none


LAK cells rest
26.1
CCD1106
4.3




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
30.6
Liver cirrhosis
2.7


LAK cells IL-2 + IL-12
18.2
Lupus kidney
3.0


LAK cells IL-2 + IFN
31.0
NCI-H292 none
76.8


gamma


LAK cells IL-2 + IL-18
31.2
NCI-H292 IL-4
94.6


LAK cells
9.5
NCI-H292 IL-9
97.3


PMA/ionomycin


NK Cells IL-2 rest
37.4
NCI-H292 IL-13
59.5


Two Way MLR 3 day
24.0
NCI-H292 IFN gamma
51.8


Two Way MLR 5 day
23.0
HPAEC none
23.3


Two Way MLR 7 day
19.6
HPAEC TNF alpha + IL-
15.8




1beta


PBMC rest
11.4
Lung fibroblast none
18.4


PBMC PWM
72.2
Lung fibroblast TNF
12.0




alpha + IL-1beta


PBMC PHA-L
33.9
Lung fibroblast IL-4
35.8


Ramos (B cell) none
19.6
Lung fibroblast IL-9
25.5


Ramos (B cell)
100.0
Lung fibroblast IL-13
18.7


ionomycin


B lymphocytes PWM
81.8
Lung fibroblast IFN
38.4




gamma


B lymphocytes CD40L
42.3
Dermal fibroblast
48.0


and IL-4

CCD1070 rest


EOL-1 dbcAMP
23.7
Dermal fibroblast
83.5




CCD1070 TNF alpha


EOL-1 dbcAMP
13.5
Dermal fibroblast
13.6


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
20.9
Dermal fibroblast IFN
13.1




gamma


Dendritic cells LPS
11.5
Dermal fibroblast IL-4
36.6


Dendritic cells anti-
23.2
IBD Colitis 2
1.8


CD40


Monocytes rest
19.2
IBD Crohn's
2.4


Monocytes LPS
6.5
Colon
26.8


Macrophages rest
36.1
Lung
21.3


Macrophages LPS
13.3
Thymus
41.5


HUVEC none
37.6
Kidney
24.3


HUVEC starved
58.6










[1948] Panel 1.3D Summary: Ag2075 Highest expression of the CG56870-01 gene is detected in the cerebral cortex (CT=24.2). Thus expression of this gene can be used in distinguishing this sample from other samples in the panel. Furthermore, significant expression of this gene is observed throughout the CNS, including in amygdala, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. The CG56870-01 gene encodes an Ndr3 homolog which is a putative member of Ndr family. This family consists of proteins from different gene families: Ndr1/RTP/Drg1/NDRG1, Ndr2, and Ndr3 (PFAM: IPR004142). NDRG1 is a cytoplasmic protein involved in stress responses, hormone responses, cell growth, and differentiation. Mutation of this gene was reported to be causative for hereditary motor and sensory neuropathy-Lom. Recently, NDRG4, another memember of Ndr family, was shown to be expressed in neurons of the brain and spinal cord. Its expression was markedly decreased in the brain of Alzheimer's disease patient (Zhou et al., 2001). Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[1949] This gene also has moderate levels of expression in adipose, adrenal, thyroid, liver, heart, thyroid and skeletal muscle. Thus, this gene product may be important in the pathogenesis, diagnosis and/or treatment of metabolic and endocrine disease, including Types 1 and 2 diabetes and obesity.


[1950] In addition, there appears to be substantial expression in other samples derived from breast cancer cell lines, lung cancer cell lines, renal cancer cell lines and colon cancer cell lines. Thus, therapeutic modulation of this gene could be of benefit in the treatment of breast, lung, renal or colon cancer.



REFERENCES

[1951] 1. Zhou R H, Kokame K, Tsukamoto Y, Yutani C, Kato H, Miyata T. (2001) Characterization of the human NDRG gene family: a newly identified member, NDRG4, is specifically expressed in brain and heart. Genomics 73(1):86-97


[1952] Ag2075 The expression of this gene appears to be highest in a sample derived from a normal brain tissue. In addition, there appears to be substantial expression in other samples derived from breast cancer cell lines, lung cancer cell lines, renal cancer cell lines and colon cancer cell lines. Thus, the expression of this gene could be used to distinguish normal brain tissue from other samples in the panel. Moreover, therapeutic modulation of this gene could be of benefit in the treatment of breast, lung, renal or colon cancer.


[1953] Panel 2.2 Summary: Ag2075 Highest expression of CG56870-01 is detected in breast cancer sample (CT=29.89). Thus expression of this gene can be used in distinguishing this sample from other samples in the panel. In addition, there appears to be substantial expression in other samples derived from breast cancers, kidney cancers and colon cancers. Therefore, therapeutic modulation of this could be of benefit in the treatment of breast, kidney or colon cancer.


[1954] Panel 3D Summary: Ag2075 The expression of this gene appears to be highest in a sample derived from a lung cancer cell line (DMS-79)(CT=26.4). In addition, there appears to be substantial expression in other samples derived from pancreatic cancer cell lines, lung cancer cell lines, brain cancer cell lines and cervical cancer cell lines. Thus, the expression of this gene could be used to distinguish DMS-79 cells from other samples in the panel. Moreover, therapeutic modulation of this gene could be of benefit in the treatment of pancreatic, lung, brain or cervical cancer.


[1955] Panel 4D Summary: Ag2075 Expression of the CG56870-01 gene is ubiquitous througout this panel, with highest in samples derived from ionomycin treated Ramos (B cell) cells (CT=26.1). Furthermore, expression of this gene is also detected in PWM treated PBMC cells and PWM treated B lymphocytes. Therefore, therapeutic modulation of the express ion or function of this gene may reduce or eliminate the symptoms in patients with autoimmune and inflammatory diseases in which B cells play a part in the initiation or progression of the disease process, such as systemic lupus erythematosus, Crohn's disease, ulcerative colitis, multiple sclerosis, chronic obstructive pulmonary disease, asthma, emphysema, rheumatoid arthritis, or psoriasis.


[1956] CD. CG56870-04: N-myc Downstream-Regulated Gene 3


[1957] Expression of gene CG56870-04 was assessed using the primer-probe sets Ag5279 and Ag2075, described in Tables CDA and CDB. Results of the RTQ-PCR runs are shown in Tables CDC, CDD, CDE, CDF, CDG, CDH and CDI.


[1958] Table CDA. Probe Name Ag5279
958TABLE CDAProbe Name Ag5279StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-aggctgtgatggcggact-3′18873650ProbeTET-5′-ttcagcctgggaagttcaccgaggcc-3′-TAMRA26912651Reverse5′-gccgagtcatgctggcagat-3′20973652


[1959] Table CDB. Probe Name Ag2075
959TABLE CDBProbe Name Ag2075StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-catggatgaacttcaggatgtt-3′2270653ProbeTET-5′-cagctcacagagatcaaaccacttct-3′-TAMRA2692654Reverse5′-tgacagtcaaagtcctggaagt-3′22141655


[1960]

960





TABLE CDC










CNS_neurodegeneration_v1.0













Rel. Exp.



Rel. Exp. (%)

(%) Ag5279,



Ag5279, Run

Run


Tissue Name
230512909
Tissue Name
230512909













AD 1 Hippo
7.7
Control (Path) 3
1.0




Temporal Ctx


AD 2 Hippo
8.4
Control (Path) 4
13.2




Temporal Ctx


AD 3 Hippo
3.4
AD 1 Occipital
7.2




Ctx


AD 4 Hippo
2.8
AD 2 Occipital
0.0




Ctx (Missing)


AD 5 hippo
100.0
AD 3 Occipital
2.1




Ctx


AD 6 Hippo
32.8
AD 4 Occipital
13.1




Ctx


Control 2 Hippo
32.3
AD 5 Occipital
15.6




Ctx


Control 4 Hippo
2.7
AD 6 Occipital
54.7




Ctx


Control (Path) 3
1.2
Control 1 Occipital
1.1


Hippo

Ctx


AD 1 Temporal Ctx
6.4
Control 2 Occipital
81.2




Ctx


AD 2 Temporal Ctx
17.1
Control 3 Occipital
8.1




Ctx


AD 3 Temporal Ctx
2.3
Control 4 Occipital
2.5




Ctx


AD 4 Temporal Ctx
8.7
Control (Path) 1
66.0




Occipital Ctx


AD 5 Inf Temporal
79.0
Control (Path) 2
5.6


Ctx

Occipital Ctx


AD 5 SupTemporal
6.4
Control (Path) 3
1.5


Ctx

Occipital Ctx


AD 6 Inf Temporal
25.7
Control (Path) 4
7.6


Ctx

Occipital Ctx


AD 6 Sup Temporal
24.1
Control 1 Parietal
2.4


Ctx

Ctx


Control 1 Temporal
2.0
Control 2 Parietal
10.7


Ctx

Ctx


Control 2 Temporal
41.2
Control 3 Parietal
16.6


Ctx

Ctx


Control 3 Temporal
4.6
Control (Path) 1
75.3


Ctx

Parietal Ctx


Control 4 Temporal
2.7
Control (Path) 2
13.7


Ctx

Parietal Ctx


Control (Path) 1
35.4
Control (Path) 3
1.6


Temporal Ctx

Parietal Ctx


Control (Path) 2
27.7
Control (Path) 4
19.3


Temporal Ctx

Parietal Ctx










[1961]

961





TABLE CDD










General_screening_panel_v1.5











Rel. Exp.

Rel. Exp.



(%) Ag5279,

(%) Ag5279,



Run

Run


Tissue Name
230509998
Tissue Name
230509998













Adipose
1.3
Renal ca. TK-10
9.2


Melanoma*
7.6
Bladder
2.4


Hs688(A).T


Melanoma*
8.0
Gastric ca. (liver met.)
8.7


Hs688(B).T

NCI-N87


Melanoma* M14
12.2
Gastric ca. KATO III
21.8


Melanoma*
13.8
Colon ca. SW-948
4.6


LOXIMVI


Melanoma* SK-
8.2
Colon ca. SW480
14.1


MEL-5


Squamous cell
6.5
Colon ca.* (SW480
10.4


carcinoma SCC-4

met) SW620


Testis Pool
8.2
Colon ca. HT29
12.3


Prostate ca.* (bone
2.3
Colon ca. HCT-116
12.2


met) PC-3


Prostate Pool
6.2
Colon ca. CaCo-2
17.8


Placenta
3.5
Colon cancer tissue
4.9


Uterus Pool
1.4
Colon ca. SW1116
2.6


Ovarian ca.
8.8
Colon ca. Colo-205
7.3


OVCAR-3


Ovarian ca. SK-
20.4
Colon ca. SW-48
5.9


OV-3


Ovarian ca.
5.6
Colon Pool
5.1


OVCAR-4


Ovarian ca.
10.9
Small Intestine Pool
3.9


OVCAR-5


Ovarian ca.
6.0
Stomach Pool
2.3


IGROV-1


Ovarian ca.
5.5
Bone Marrow Pool
1.5


OVCAR-8


Ovary
5.7
Fetal Heart
7.5


Breast ca. MCF-7
5.0
Heart Pool
3.3


Breast ca. MDA-
23.0
Lymph Node Pool
5.1


MB-231


Breast ca. BT 549
21.9
Fetal Skeletal Muscle
3.1


Breast ca. T47D
10.6
Skeletal Muscle Pool
4.0


Breast ca. MDA-N
5.8
Spleen Pool
2.2


Breast Pool
5.9
Thymus Pool
2.9


Trachea
5.0
CNS cancer
20.4




(glio/astro) U87-MG


Lung
2.5
CNS cancer
16.8




(glio/astro) U-118-MG


Fetal Lung
8.7
CNS cancer
10.7




(neuro; met) SK-N-AS


Lung ca. NCI-N417
3.7
CNS cancer (astro)
7.0




SF-539


Lung ca. LX-1
12.1
CNS cancer (astro)
21.3




SNB-75


Lung ca. NCI-H146
5.8
CNS cancer (glio)
5.8




SNB-19


Lung ca. SHP-77
7.9
CNS cancer (glio) SF-
12.2




295


Lung ca. A549
14.1
Brain (Amygdala)
19.3




Pool


Lung ca. NCI-H526
5.1
Brain (cerebellum)
100.0


Lung ca. NCI-H23
11.2
Brain (fetal)
20.0


Lung ca. NCI-H460
2.9
Brain (Hippocampus)
17.4




Pool


Lung ca. HOP-62
4.6
Cerebral Cortex Pool
23.7


Lung ca. NCI-H522
13.6
Brain (Substantia
17.9




nigra) Pool


Liver
0.5
Brain (Thalamus) Pool
34.2


Fetal Liver
3.2
Brain (whole)
46.3


Liver ca. HepG2
5.3
Spinal Cord Pool
9.5


Kidney Pool
7.1
Adrenal Gland
11.8


Fetal Kidney
5.7
Pituitary gland Pool
2.9


Renal ca. 786-0
6.3
Salivary Gland
3.5


Renal ca. A498
11.0
Thyroid (female)
2.0


Renal ca. ACHN
6.0
Pancreatic ca.
5.6




CAPAN2


Renal ca. UO-31
8.0
Pancreas Pool
6.2










[1962]

962





TABLE CDE










Panel 1.3D











Rel. Exp. (%)

Rel. Exp. (%)



Ag2075, Run

Ag2075,


Tissue Name
Run 152355202
Tissue Name
Run 152355202













Liver adenocarcinoma
11.9
Kidney (fetal)
1.4


Pancreas
0.8
Renal ca. 786-0
3.5


Pancreatic ca. CAPAN 2
1.6
Renal ca. A498
12.9


Adrenal gland
2.4
Renal ca. RXF 393
1.5


Thyroid
1.8
Renal ca. ACHN
1.7


Salivary gland
1.2
Renal ca. UO-31
6.8


Pituitary gland
2.4
Renal ca. TK-10
2.8


Brain (fetal)
3.2
Liver
0.4


Brain (whole)
25.2
Liver (fetal)
0.8


Brain (amygdala)
14.1
Liver ca.
6.7




(hepatoblast) HepG2


Brain (cerebellum)
10.8
Lung
2.1


Brain (hippocampus)
39.8
Lung (fetal)
3.2


Brain (substantia nigra)
2.7
Lung ca. (small cell)
4.1




LX-1


Brain (thalamus)
12.4
Lung ca. (small cell)
3.8




NCI-H69


Cerebral Cortex
100.0
Lung ca. (s.cell var.)
3.8




SHP-77


Spinal cord
3.5
Lung ca. (large
0.6




cell)NCI-H460


glio/astro U87-MG
6.4
Lung ca. (non-sm.
3.0




cell) A549


glio/astro U-118-MG
10.4
Lung ca. (non-s.cell)
7.7




NCI-H23


astrocytoma SW1783
5.1
Lung ca. (non-s.cell)
3.1




HOP-62


neuro*; met SK-N-AS
6.2
Lung ca. (non-s.cl)
6.3




NCI-H522


astrocytoma SF-539
5.4
Lung ca. (squam.)
1.4




SW 900


astrocytoma SNB-75
6.7
Lung ca. (squam.)
1.4




NCI-H596


glioma SNB-19
3.1
Mammary gland
2.4


glioma U251
2.0
Breast ca.* (pl.ef)
1.8




MCF-7


glioma SF-295
3.4
Breast ca.* (pl.ef)
11.6




MDA-MB-231


Heart (fetal)
6.7
Breast ca.* (pl.ef)
9.0




T47D


Heart
1.4
Breast ca. BT-549
4.8


Skeletal muscle (fetal)
18.0
Breast ca. MDA-N
4.2


Skeletal muscle
0.7
Ovary
13.4


Bone marrow
0.9
Ovarian ca.
1.8




OVCAR-3


Thymus
0.9
Ovarian ca.
1.6




OVCAR-4


Spleen
3.7
Ovarian ca.
1.8




OVCAR-5


Lymph node
1.9
Ovarian ca.
4.9




OVCAR-8


Colorectal
3.3
Ovarian ca. IGROV-1
1.6


Stomach
2.7
Ovarian ca.*
5.8




(ascites) SK-OV-3


Small intestine
2.5
Uterus
2.4


Colon ca. SW480
10.4
Placenta
1.2


Colon ca.*
3.7
Prostate
6.0


SW620(SW480 met)


Colon ca. HT29
4.6
Prostate ca.* (bone
4.5




met)PC-3


Colon ca. HCT-116
3.6
Testis
1.7


Colon ca. CaCo-2
10.3
Melanoma
3.8




Hs688(A).T


Colon ca.
3.2
Melanoma* (met)
4.4


tissue(ODO3866)

Hs688(B).T


Colon ca. HCC-2998
2.6
Melanoma UACC-
1.4




62


Gastric ca.* (liver met)
3.1
Melanoma M14
1.8


NCI-N87


Bladder
0.8
Melanoma LOX
3.3




IMVI


Trachea
2.0
Melanoma* (met)
2.4




SK-MEL-5


Kidney
1.3
Adipose
1.2










[1963]

963





TABLE CDF










Panel 2.2











Rel. Exp. (%)

Rel. Exp. (%)



Ag2075, Run

Ag2075,


Tissue Name
174255357
Tissue Name
Run 174255357













Normal Colon
27.7
Kidney Margin
46.3




(OD04348)


Colon cancer
52.9
Kidney malignant
19.2


(OD06064)

cancer (OD06204B)


Colon Margin
30.1
Kidney normal
14.3


(OD06064)

adjacent tissue




(OD06204E)


Colon cancer
5.5
Kidney Cancer
66.0


(OD06159)

(OD04450-01)


Colon Margin
21.0
Kidney Margin
19.8


(OD06159)

(OD04450-03)


Colon cancer
22.2
Kidney Cancer
3.0


(OD06297-04)

8120613


Colon Margin
41.8
Kidney Margin
11.0


(OD06297-05)

8120614


CC Gr.2 ascend colon
4.0
Kidney Cancer
6.8


(ODO3921)

9010320


CC Margin (ODO3921)
6.7
Kidney Margin
9.7




9010321


Colon cancer metastasis
11.1
Kidney Cancer
35.6


(OD06104)

8120607


Lung Margin
42.6
Kidney Margin
13.7


(OD06104)

8120608


Colon mets to lung
17.8
Normal Uterus
59.5


(OD04451-01)


Lung Margin
9.3
Uterine Cancer 064011
9.7


(OD04451-02)


Normal Prostate
51.4
Normal Thyroid
8.8


Prostate Cancer
23.0
Thyroid Cancer
11.2


(OD04410)

064010


Prostate Margin
19.3
Thyroid Cancer
17.9


(OD04410)

A302152


Normal Ovary
22.8
Thyroid Margin
5.5




A302153


Ovarian cancer
9.9
Normal Breast
33.2


(OD06283-03)


Ovarian Margin
17.1
Breast Cancer
8.5


(OD06283-07)

(OD04566)


Ovarian Cancer 064008
18.0
Breast Cancer 1024
36.1


Ovarian cancer
6.6
Breast Cancer
18.4


(OD06145)

(OD04590-01)


Ovarian Margin
12.5
Breast Cancer Mets
31.9


(OD06145)

(OD04590-03)


Ovarian cancer
14.7
Breast Cancer
45.4


(OD06455-03)

Metastasis (OD04655-




05)


Ovarian Margin
21.8
Breast Cancer 064006
11.5


(OD06455-07)


Normal Lung
21.9
Breast Cancer 9100266
20.9


Invasive poor diff. lung
17.6
Breast Margin
35.1


adeno (ODO4945-01)

9100265


Lung Margin
12.2
Breast Cancer
9.7


(ODO4945-03)

A209073


Lung Malignant Cancer
8.7
Breast Margin
22.2


(OD03126)

A2090734


Lung Margin
7.4
Breast cancer
100.0


(OD03126)

(OD06083)


Lung Cancer
9.9
Breast cancer node
63.7


(OD05014A)

metastasis (OD06083)


Lung Margin
21.8
Normal Liver
9.9


(OD05014B)


Lung cancer
5.1
Liver Cancer 1026
5.6


(OD06081)


Lung Margin
7.9
Liver Cancer 1025
13.5


(OD06081)


Lung Cancer
17.4
Liver Cancer 6004-T
4.8


(OD04237-01)


Lung Margin
24.0
Liver Tissue 6004-N
9.3


(OD04237-02)


Ocular Melanoma
9.7
Liver Cancer 6005-T
15.7


Metastasis


Ocular Melanoma
4.6
Liver Tissue 6005-N
20.4


Margin (Liver)


Melanoma Metastasis
19.8
Liver Cancer 064003
10.7


Melanoma Margin
21.6
Normal Bladder
8.0


(Lung)


Normal Kidney
11.0
Bladder Cancer 1023
10.5


Kidney Ca, Nuclear
37.6
Bladder Cancer
17.3


grade 2 (OD04338)

A302173


Kidney Margin
22.1
Normal Stomach
37.9


(OD04338)


Kidney Ca Nuclear
21.6
Gastric Cancer
11.1


grade 1/2 (OD04339)

9060397


Kidney Margin
12.9
Stomach Margin
20.6


(OD04339)

9060396


Kidney Ca, Clear cell
6.5
Gastric Cancer
22.7


type (OD04340)

9060395


Kidney Margin
18.4
Stomach Margin
36.1


(OD04340)

9060394


Kidney Ca, Nuclear
12.9
Gastric Cancer 064005
8.1


grade 3 (OD04348)










[1964]

964





TABLE CDG










Panel 3D











Rel. Exp. (%)

Rel. Exp. (%)



Ag2075, Run

Ag2075, Run


Tissue Name
164750734
Tissue Name
164750734













Daoy-Medulloblastoma
6.7
Ca Ski-Cervical epidermoid
50.3




carcinoma (metastasis)


TE671-
9.0
ES-2-Ovarian clear cell
13.9


Medulloblastoma

carcinoma


D283 Med-
35.4
Ramos-Stimulated with
2.7


Medulloblastoma

PMA/ionomycin 6 h


PFSK-1-Primitive
15.4
Ramos-Stimulated with
3.3


Neuroectodermal

PMA/ionomycin 14 h


XF-498-CNS
4.4
MEG-01-Chronic
3.4




myelogenous leukemia




(megokaryoblast)


SNB-78-Glioma
23.3
Raji-Burkitt's lymphoma
3.7


SF-268-Glioblastoma
13.6
Daudi-Burkitt's lymphoma
6.5


T98G-Glioblastoma
18.6
U266-B-cell plasmacytoma
8.4


SK-N-SH-
17.0
CA46-Burkitt's lymphoma
7.2


Neuroblastoma


(metastasis)


SF-295-Glioblastoma
8.4
RL-non-Hodgkin's B-cell
3.5




lymphoma


Cerebellum
74.7
JM1-pre-B-cell lymphoma
3.1


Cerebellum
62.4
Jurkat-T cell leukemia
11.6


NCI-H292-
45.7
TF-1-Erythroleukemia
13.4


Mucoepidermoid lung


carcinoma


DMS-114-Small cell
10.9
HUT 78-T-cell lymphoma
10.0


lung cancer


DMS-79-Small cell
100.0
U937-Histiocytic lymphoma
18.2


lung cancer


NCI-H146-Small cell
30.6
KU-812-Myelogenous
6.0


lung cancer

leukemia


NCI-H526-Small cell
57.4
769-P-Clear cell renal
11.3


lung cancer

carcinoma


NCI-N417-Small cell
15.2
Caki-2-Clear cell renal
10.4


lung cancer

carcinoma


NCI-H82-Small cell
36.9
SW 839-Clear cell renal
2.2


lung cancer

carcinoma


NCI-H157-Squamous
51.1
G401-Wilms' tumor
6.2


cell lung cancer


(metastasis)


NCI-H1155-Large cell
26.6
Hs766T-Pancreatic
42.9


lung cancer

carcinoma (LN metastasis)


NCI-H1299-Large cell
44.4
CAPAN-1-Pancreatic
5.0


lung cancer

adenocarcinoma (liver




metastasis)


NCI-H727-Lung
47.0
SU86.86-Pancreatic
28.1


carcinoid

carcinoma (liver metastasis)


NCI-UMC-11-Lung
60.3
BxPC-3-Pancreatic
6.3


carcinoid

adenocarcinoma


LX-1-Small cell lung
23.5
HPAC-Pancreatic
7.4


cancer

adenocarcinoma


Colo-205-Colon cancer
29.5
MIA PaCa-2-Pancreatic
3.6




carcinoma


KM12-Colon cancer
24.0
CFPAC-1-Pancreatic ductal
40.9




adenocarcinoma


KM20L2-Colon cancer
8.4
PANC-1-Pancreatic
20.9




epithelioid ductal carcinoma


NCI-H716-Colon
23.3
T24-Bladder carcinma
13.1


cancer

(transitional cell)


SW-48-Colon
27.0
5637-Bladder carcinoma
11.0


adenocarcinoma


SW1116-Colon
10.0
HT-1197-Bladder
9.2


adenocarcinoma

carcinoma


LS 174T-Colon
9.9
UM-UC-3-Bladder
7.2


adenocarcinoma

carcinma (transitional cell)


SW-948-Colon
1.1
A204-Rhabdomyosarcoma
7.0


adenocarcinoma


SW-480-Colon
8.8
HT-1080-Fibrosarcoma
16.6


adenocarcinoma


NCI-SNU-5-Gastric
7.2
MG-63-Osteosarcoma
16.7


carcinoma


KATO III-Gastric
32.8
SK-LMS-1-
26.4


carcinoma

Leiomyosarcoma (vulva)


NCI-SNU-16-Gastric
13.6
SJRH30-
16.8


carcinoma

Rhabdomyosarcoma (met to




bone marrow)


NCI-SNU-1-Gastric
16.0
A431-Epidermoid
9.8


carcinoma

carcinoma


RF-1-Gastric
2.1
WM266-4-Melanoma
12.0


adenocarcinoma


RF-48-Gastric
4.0
DU 145-Prostate carcinoma
0.1


adenocarcinoma

(brain metastasis)


MKN-45-Gastric
28.7
MDA-MB-468-Breast
14.7


carcinoma

adenocarcinoma


NCI-N87-Gastric
13.3
SCC-4-Squamous cell
0.9


carcinoma

carcinoma of tongue


OVCAR-5-Ovarian
2.6
SCC-9-Squamous cell
0.3


carcinoma

carcinoma of tongue


RL95-2-Uterine
7.2
SCC-15-Squamous cell
0.5


carcinoma

carcinoma of tongue


HelaS3-Cervical
13.4
CAL 27-Squamous cell
21.2


adenocarcinoma

carcinoma of tongue










[1965]

965





TABLE CDH










Panel 4.1D











Rel. Exp. (%)

Rel. Exp. (%)



Ag5279, Run

Ag5279, Run


Tissue Name
230472927
Tissue Name
230472927













Secondary Th1 act
59.0
HUVEC IL-1beta
41.5


Secondary Th2 act
91.4
HUVEC IFN gamma
71.7


Secondary Tr1 act
27.5
HUVEC TNF alpha +
17.4




IFN gamma


Secondary Th1 rest
7.5
HUVEC TNF alpha +
20.7




IL4


Secondary Th2 rest
8.4
HUVEC IL-11
32.3


Secondary Tr1 rest
2.6
Lung Microvascular EC
57.4




none


Primary Th1 act
26.8
Lung Microvascular EC
14.6




TNF alpha + IL-1beta


Primary Th2 act
55.1
Microvascular Dermal
10.9




EC none


Primary Tr1 act
55.5
Microsvasular Dermal
13.2




EC TNF alpha + IL-1beta


Primary Th1 rest
3.2
Bronchial epithelium
17.4




TNF alpha + IL1beta


Primary Th2 rest
13.7
Small airway epithelium
18.8




none


Primary Tr1 rest
7.6
Small airway epithelium
56.3




TNF alpha + IL-1beta


CD45RA CD4
31.9
Coronery artery SMC rest
31.9


lymphocyte act


CD45RO CD4
48.3
Coronery artery SMC
37.1


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
21.2
Astrocytes rest
28.3


Secondary CD8
36.1
Astrocytes TNF alpha +
15.8


lymphocyte rest

IL-1beta


Secondary CD8
8.0
KU-812 (Basophil) rest
15.2


lymphocyte act


CD4 lymphocyte none
8.4
KU-812 (Basophil)
17.0




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
8.9
CCD1106
71.2


CD95 CH11

(Keratinocytes) none


LAK cells rest
26.1
CCD1106
42.0




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
16.3
Liver cirrhosis
15.5


LAK cells IL-2 + IL-12
2.0
NCI-H292 none
45.4


LAK cells IL-2 + IFN
12.5
NCI-H292 IL-4
63.7


gamma


LAK cells IL-2 + IL-18
7.5
NCI-H292 IL-9
70.7


LAK cells
21.9
NCI-H292 IL-13
99.3


PMA/ionomycin


NK Cells IL-2 rest
44.4
NCI-H292 IFN gamma
45.4


Two Way MLR 3 day
21.9
HPAEC none
25.9


Two Way MLR 5 day
13.5
HPAEC TNF alpha + IL-
34.9




1beta


Two Way MLR 7 day
11.3
Lung fibroblast none
37.9


PBMC rest
11.0
Lung fibroblast TNF
21.2




alpha + IL-1beta


PBMC PWM
4.5
Lung fibroblast IL-4
31.6


PBMC PHA-L
18.4
Lung fibroblast IL-9
36.3


Ramos (B cell) none
14.0
Lung fibroblast IL-13
9.0


Ramos (B cell)
42.9
Lung fibroblast IFN
58.6


ionomycin

gamma


B lymphocytes PWM
18.9
Dermal fibroblast
43.2




CCD1070 rest


B lymphocytes CD40L
31.0
Dermal fibroblast
100.0


and IL-4

CCD1070 TNF alpha


EOL-1 dbcAMP
37.9
Dermal fibroblast
23.5




CCD1070 IL-1beta


EOL-1 dbcAMP
14.7
Dermal fibroblast IFN
31.4


PMA/ionomycin

gamma


Dendritic cells none
26.2
Dermal fibroblast IL-4
45.4


Dendritic cells LPS
13.2
Dermal Fibroblasts rest
61.6


Dendritic cells anti-
17.0
Neutrophils TNFA + LPS
4.2


CD40


Monocytes rest
11.6
Neutrophils rest
31.4


Monocytes LPS
8.5
Colon
1.0


Macrophages rest
12.9
Lung
1.6


Macrophages LPS
2.6
Thymus
4.5


HUVEC none
36.1
Kidney
32.5


HUVEC starved
36.9










[1966]

966





TABLE CDI










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag2075, Run

Ag2075, Run


Tissue Name
152787491
Tissue Name
152787491













Secondary Th1 act
46.3
HUVEC IL-1beta
25.0


Secondary Th2 act
39.2
HUVEC IFN gamma
33.0


Secondary Tr1 act
31.9
HUVEC TNF alpha +
13.1




IFN gamma


Secondary Th1 rest
11.7
HUVEC TNF alpha +
20.7




IL4


Secondary Th2 rest
13.9
HUVEC IL-11
20.0


Secondary Tr1 rest
21.6
Lung Microvascular EC
22.7




none


Primary Th1 act
30.1
Lung Microvascular EC
15.0




TNF alpha + IL-1beta


Primary Th2 act
39.2
Microvascular Dermal
26.8




EC none


Primary Tr1 act
54.7
Microsvasular Dermal
16.6




EC TNF alpha + IL-1beta


Primary Th1 rest
84.1
Bronchial epithelium
4.9




TNF alpha + IL1beta


Primary Th2 rest
48.6
Small airway epithelium
19.9




none


Primary Tr1 rest
39.0
Small airway epithelium
72.7




TNF alpha + IL-1beta


CD45RA CD4
21.8
Coronery artery SMC rest
27.9


lymphocyte act


CD45RO CD4
33.0
Coronery artery SMC
19.6


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
25.5
Astrocytes rest
26.4


Secondary CD8
21.5
Astrocytes TNF alpha +
13.2


lymphocyte rest

IL-1beta


Secondary CD8
29.3
KU-812 (Basophil) rest
6.3


lymphocyte act


CD4 lymphocyte none
12.7
KU-812 (Basophil)
16.0




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
25.5
CCD1106
46.0


CD95 CH11

(Keratinocytes) none


LAK cells rest
26.1
CCD1106
4.3




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
30.6
Liver cirrhosis
2.7


LAK cells IL-2 + IL-12
18.2
Lupus kidney
3.0


LAK cells IL-2 + IFN
31.0
NCI-H292 none
76.8


gamma


LAK cells IL-2 + IL-18
31.2
NCI-H292 IL-4
94.6


LAK cells
9.5
NCI-H292 IL-9
97.3


PMA/ionomycin


NK Cells IL-2 rest
37.4
NCI-H292 IL-13
59.5


Two Way MLR 3 day
24.0
NCI-H292 IFN gamma
51.8


Two Way MLR 5 day
23.0
HPAEC none
23.3


Two Way MLR 7 day
19.6
HPAEC TNF alpha + IL-
15.8




1beta


PBMC rest
11.4
Lung fibroblast none
18.4


PBMC PWM
72.2
Lung fibroblast TNF
12.0




alpha + IL-1beta


PBMC PHA-L
33.9
Lung fibroblast IL-4
35.8


Ramos (B cell) none
19.6
Lung fibroblast IL-9
25.5


Ramos (B cell)
100.0
Lung fibroblast IL-13
18.7


ionomycin


B lymphocytes PWM
81.8
Lung fibroblast IFN
38.4




gamma


B lymphocytes CD40L
42.3
Dermal fibroblast
48.0


and IL-4

CCD1070 rest


EOL-1 dbcAMP
23.7
Dermal fibroblast
83.5




CCD1070 TNF alpha


EOL-1 dbcAMP
13.5
Dermal fibroblast
13.6


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
20.9
Dermal fibroblast IFN
13.1




gamma


Dendritic cells LPS
11.5
Dermal fibroblast IL-4
36.6


Dendritic cells anti-
23.2
IBD Colitis 2
1.8


CD40


Monocytes rest
19.2
IBD Crohn's
2.4


Monocytes LPS
6.5
Colon
26.8


Macrophages rest
36.1
Lung
21.3


Macrophages LPS
13.3
Thymus
41.5


HUVEC none
37.6
Kidney
24.3


HUVEC starved
58.6










[1967] CNS_neurodegeneration_v1.0 Summary: Ag5279 This panel confirms the expression of the CG56870-04 gene at low levels in the brain in an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.5 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.


[1968] General_screening_panel_v1.5 Summary: Ag5279 Highest expression of the CG56870-01 is detected in cerebral cortex (CT=25.02). Thus, expression of this gene can be used in distinguishing this sample from other samples in the panel. Furthermore, significant expression of this gene is observed throughout the CNS, including in amygdala, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. The CG56870-01 gene encodes a Ndr3 protein homolog. The Ndr family is comprised of members from different gene families: Ndr1/RTP/Drg1/NDRG1, Ndr2, and Ndr3 (PFAM: IPR004142). NDRG1 is a cytoplasmic protein involved in stress responses, hormone responses, cell growth, and differentiation. Mutation of this gene was reported to be causative for hereditary motor and sensory neuropathy-Lom. Recently, NDRG4, another memember of Ndr family, was shown to be expressed in neurons of the brain and spinal cord. Its expression was markedly decreased in the brain of Alzheimer's disease patient (Zhou et al., 2001). Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[1969] Among metabolic tissues, this gene is moderately expressed in adipose, adrenal, heart, thyroid, liver, pancreas, pituitary, and skeletal muscle. Thus, this gene product may be important for the pathogenesis, diagnosis, and/or treatment of metabolic and endocrine disease, including Types 1 and 2 diabetes and obesity.


[1970] In addition, there appears to be substantial expression in other samples derived from brain cancer cell lines, colon cancer cell lines, breast cancer cell lines and ovarian cancer cell lines. Moreover, therapeutic modulation of this gene could be of benefit in the treatment of brain, colon, breast or ovarian cancer.



REFERENCES

[1971] 1. Zhou R H, Kokame K, Tsukamoto Y, Yutani C, Kato H, Miyata T. (2001) Characterization of the human NDRG gene family: a newly identified member, NDRG4, is specifically expressed in brain and heart. Genomics 73(1):86-97


[1972] Panel 1.3D Summary: Ag2075 Highest expression of the CG56870-01 gene is detected in the cerebral cortex (CT=24.2). This expression is consistent with expression in Panel 1.5. Please see that panel for discussion of utility of this gene in the central nervous system.


[1973] This gene also has moderate levels of expression in adipose, adrenal, thyroid, liver, heart, thyroid and skeletal muscle. Thus, this gene product may be important in the pathogenesis, diagnosis and/or treatment of metabolic and endocrine disease, including Types 1 and 2 diabetes and obesity.


[1974] In addition, there appears to be substantial expression in other samples derived from breast cancer cell lines, lung cancer cell lines, renal cancer cell lines and colon cancer cell lines. Thus, therapeutic modulation of this gene could be of benefit in the treatment of breast, lung, renal or colon cancer.


[1975] Panel 2.2 Summary: Ag2075 Highest expression of CG56870-01 is detected in breast cancer sample (CT=29.89). Thus expression of this gene can be used in distinguishing this sample from other samples in the panel. In addition, there appears to be substantial expression in other samples derived from breast cancers, kidney cancers and colon cancers. Therefore, therapeutic modulation of this gene could be of benefit in the treatment of breast, kidney or colon cancer.


[1976] Panel 3D Summary: Ag2075 The expression of this gene appears to be highest in a sample derived from a lung cancer cell line (DMS-79)(CT=26.4). In addition, there appears to be substantial expression in other samples derived from pancreatic cancer cell lines, lung cancer cell lines, brain cancer cell lines and cervical cancer cell lines. Thus, the expression of this gene could be used to distinguish DMS-79 cells from other samples in the panel. Moreover, therapeutic modulation of this gene could be of benefit in the treatment of pancreatic, lung, brain or cervical cancer.


[1977] Panel 4.1D Summary: Ag5279 Expression of the CG56870-01 gene is highest in samples derived from TNF alpha treated dermal fibroblast CCD1070 cells (CT=30.6). Expression of this gene is also prominent in activated secondary and primarey Th1, Th2 and Tr1 cells when compared expression in the corresponding resting cell lines. Thus, this gene may be involved in T lymphocyte function. Therefore, therapeutic modulation to the expression or function of this gene may be as anti-inflammatory therapeutics for T cell-mediated autoimmune and inflammatory diseases, such as asthma, athritis, psoriasis, IBD, and lupus.


[1978] Panel 4D Summary: Ag2075 Expression of the CG56870-01 gene is ubiquitous throughout this panel, with highest in samples derived from ionomycin treated Ramos (B cell) cells (CT=26.1). Furthermore, expression of this gene is also detected in PWM treated PBMC cells and PWM treated B lymphocytes. Therefore, therapeutic modulation of the expression or function of this gene may reduce or eliminate the symptoms in patients with autoimmune and inflammatory diseases in which B cells play a part in the initiation or progression of the disease process, such as systemic lupus erythematosus, Crohn's disease, ulcerative colitis, multiple sclerosis, chronic obstructive pulmonary disease, asthma, emphysema, rheumatoid arthritis, or psoriasis.


[1979] CE. CG!56870-05: N-myc Downstream-Regulated Gene 3


[1980] Expression of gene CG56870-05 was assessed using the primer-probe set Ag5265, described in Table CEA. Results of the RTQ-PCR runs are shown in Tables CEB and CEC.


[1981] Table CEA. Probe Name Ag5265
967TABLE CEAProbe Name Ag5265StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-tgttcagctcacagagatcaaa-3′2218656ProbeTET-5′-caagaaacttccaggactttgactgtca-3′-TAMRA2865657Reverse5′-catccattgtggggtactga-3′2096658


[1982]

968





TABLE CEB










CNS_neurodegeneration_v1.0













Rel. Exp.



Rel. Exp. (%)

(%) Ag5265,



Ag5265, Run

Run


Tissue Name
230512714
Tissue Name
230512714













AD 1 Hippo
7.2
Control (Path) 3
2.4




Temporal Ctx


AD 2 Hippo
15.2
Control (Path) 4
10.3




Temporal Ctx


AD 3 Hippo
2.0
AD 1 Occipital Ctx
11.5


AD 4 Hippo
3.3
AD 2 Occipital Ctx
0.0




(Missing)


AD 5 Hippo
59.9
AD 3 Occipital Ctx
7.0


AD 6 Hippo
22.1
AD 4 Occipital Ctx
6.9


Control 2 Hippo
14.5
AD 5 Occipital Ctx
54.7


Control 4 Hippo
2.6
AD 6 Occipital Ctx
12.2


Control (Path) 3
3.9
Control 1 Occipital
1.2


Hippo

Ctx


AD 1 Temporal
12.7
Control 2 Occipital
60.3


Ctx

Ctx


AD 2 Temporal
16.0
Control 3 Occipital
8.2


Ctx

Ctx


AD 3 Temporal
5.5
Control 4 Occipital
1.7


Ctx

Ctx


AD 4 Temporal
13.9
Control (Path) 1
53.6


Ctx

Occipital Ctx


AD 5 Inf Temporal
64.6
Control (Path) 2
5.9


Ctx

Occipital Ctx


AD 5 Sup
28.9
Control (Path) 3
2.2


Temporal Ctx

Occipital Ctx


AD 6 Inf Temporal
27.0
Control (Path) 4
5.5


Ctx

Occipital Ctx


AD 6 Sup
100.0
Control 1 Parietal
3.0


Temporal Ctx

Ctx


Control 1
2.6
Control 2 Parietal
19.6


Temporal Ctx

Ctx


Control 2
38.2
Control 3 Parietal
18.8


Temporal Ctx

Ctx


Control 3
9.7
Control (Path) 1
56.6


Temporal Ctx

Parietal Ctx


Control 3
1.5
Control (Path) 2
14.2


Temporal Ctx

Parietal Ctx


Control (Path) 1
31.4
Control (Path) 3
2.6


Temporal Ctx

Parietal Ctx


Control (Path) 2
18.3
Control (Path) 4
25.0


Temporal Ctx

Parietal Ctx










[1983]

969





TABLE CEC










General_screening_panel_v1.5











Rel. Exp.

Rel. Exp.



(%) Ag5265,

(%) Ag5265,



Run

Run


Tissue Name
232936652
Tissue Name
232936652













Adipose
1.1
Renal ca. TK-10
14.8


Melanoma*
7.9
Bladder
2.5


Hs688(A).T


Melanoma*
10.1
Gastric ca. (liver met.)
7.3


Hs688(B).T

NCI-N87


Melanorna* M14
12.4
Gastric ca. KATO III
17.8


Melanoma*
13.7
Colon ca. SW-948
1.8


LOXIMVI


Melanoma* SK-
9.9
Colon ca. SW480
16.0


MEL-5


Squamous cell
8.3
Colon ca.* (SW480
8.2


carcinoma SCC-4

met) SW620


Testis Pool
2.2
Colon ca. HT29
6.7


Prostate ca.* (bone
18.0
Colon ca. HCT-116
15.8


met) PC-3


Prostate Pool
4.4
Colon ca. CaCo-2
25.5


Placenta
2.1
Colon cancer tissue
2.5


Uterus Pool
1.9
Colon ca. SW1116
2.3


Ovarian ca.
9.0
Colon ca. Colo-205
4.8


OVCAR-3


Ovarian ca. SK-
16.0
Colon ca. SW-48
5.1


OV-3


Ovarian ca.
4.5
Colon Pool
2.8


OVCAR-4


Ovarian ca.
10.4
Small Intestine Pool
2.4


OVCAR-5


Ovarian ca.
12.0
Stomach Pool
1.8


IGROV-1


Ovarian ca.
4.5
Bone Marrow Pool
1.2


OVCAR-8


Ovary
2.8
Fetal Heart
2.3


Breast ca. MCF-7
4.9
Heart Pool
1.5


Breast ca. MDA-
30.1
Lymph Node Pool
3.0


MB-231


Breast ca. BT 549
18.9
Fetal Skeletal Muscle
0.9


Breast ca. T47D
4.0
Skeletal Muscle Pool
1.8


Breast ca. MDA-N
8.4
Spleen Pool
2.2


Breast Pool
3.6
Thymus Pool
1.9


Trachea
3.2
CNS cancer
18.3




(glio/astro) U87-MG


Lung
1.7
CNS cancer
19.5




(glio/astro) U-118-MG


Fetal Lung
4.8
CNS cancer
8.4




(neuro; met) SK-N-AS


Lung ca. NCI-N417
2.0
CNS cancer (astro)
8.8




SF-539


Lung ca. LX-1
8.5
CNS cancer (astro)
29.1




SNB-75


Lung ca. NCI-H146
9.2
CNS cancer (glio)
10.9




SNB-19


Lung ca. SHP-77
8.2
CNS cancer (glio) SF-
17.2




295


Lung ca. A549
15.2
Brain (Amygdala)
14.0




Pool


Lung ca. NCI-H526
3.2
Brain (cerebellum)
100.0


Lung ca. NCI-H23
16.2
Brain (fetal)
10.7


Lung ca. NCI-H460
2.7
Brain (Hippocampus)
11.4




Pool


Lung ca. HOP-62
5.6
Cerebral Cortex Pool
15.5


Lung ca. NCI-H522
13.0
Brain (Substantia
14.7




nigra) Pool


Liver
0.9
Brain (Thalamus) Pool
17.9


Fetal Liver
2.4
Brain (whole)
25.9


Liver ca. HepG2
6.2
Spinal Cord Pool
9.0


Kidney Pool
6.9
Adrenal Gland
5.0


Fetal Kidney
3.1
Pituitary gland Pool
1.5


Renal ca. 786-0
9.0
Salivary Gland
2.3


Renal ca. A498
7.6
Thyroid (female)
2.0


Renal ca. ACHN
6.0
Pancreatic ca.
6.5




CAPAN2


Renal ca. UO-31
6.3
Pancreas Pool
3.2










[1984] CNS_neurodegeneration_v1.0 Summary: Ag5265 This panel confirms the expression of the CG56870-04 gene at low levels in the brain in an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.5 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.


[1985] General_screening_panel_v1.5 Summary: Ag5265 Highest expression of the CG56870-05 gene is detected in cerebral cortex (CT=28.86). Thus, expression of this gene can be used in distinguishing this sample from other samples in the panel. Furthermore, significant expression of this gene is observed throughout the CNS, including in amygdala, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. The CG56870-05 gene encodes a putative Ndr3 protein. This family consists of proteins from different gene families: Ndr1/RTP/Drg1/NDRG1, Ndr2, and Ndr3 (PFAM: IPR004142). NDRG1 is a cytoplasmic protein involved in stress responses, hormone responses, cell growth, and differentiation. Mutation of this gene was reported to be causative for hereditary motor and sensory neuropathy-Lom. Recently, NDRG4, another memember of Ndr family, was shown to be expressed in neurons of the brain and spinal cord. Its expression was markedly decreased in the brain of Alzheimer's disease patient (Zhou et al., 2001). Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[1986] Among metabolic tissues, this gene has low levels of expression in heart, skeletal muscle, adrenal, thyroid, pancreas and pituitary. Therefore, this gene product may be important for the pathogenesis, diagnosis, and/or treatment of metabolic and endocrine disease, including Types 1 and 2 diabetes and obesity.


[1987] Overall, this gene is expressed in all the samples on this panel, with slightly higher levels of expression in the cancer cell lines compared to expression in the normal tissues samples.


[1988] Panel 4.1D Summary: Ag5265 Expression of this gene is low/undetectable (CTs>34.5) across all of the samples on this panel (data not shown).


[1989] sCF. CG59764-01: Ferritin Heavy Chain Like Protein


[1990] Expression of gene CG59764-01 was assessed using the primer-probe set Ag3578, described in Table CFA. Results of the RTQ-PCR runs are shown in Tables CFB and CFC.


[1991] Table CFA. Probe Name Ag3578
970TABLE CFAProbe Name Ag3578StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-ctgcgacttcctggagaac-3′19430659ProbeTET-5′-agcaggccaagaccatcaaagagct-3′-TAMRA25462660Reverse5′-tgtgcaggttgctcaggta-3′19494661


[1992]

971





TABLE CFB










CNS_neurodegeneration_v1.0













Rel. Exp.



Rel. Exp. (%)

(%) Ag3578,



Ag3578, Run

Run


Tissue Name
210642348
Tissue Name
210642348













AD 1 Hippo
14.0
Control (Path) 3
3.2




Temporal Ctx


AD 2 Hippo
8.2
Control (Path) 4
52.9




Temporal Ctx


AD 3 Hippo
6.7
AD 1 Occipital Ctx
22.8


AD 4 Hippo
2.3
AD 2 Occipital Ctx
0.0




(Missing)


AD 5 Hippo
83.5
AD 3 Occipital Ctx
7.3


AD 6 Hippo
29.1
AD 4 Occipital Ctx
14.9


Control 2 Hippo
1.6
AD 5 Occipital Ctx
11.4


Control 4 Hippo
3.1
AD 6 Occipital Ctx
19.8


Control (Path) 3
8.0
Control 1 Occipital
9.0


Hippo

Ctx


AD 1 Temporal
19.5
Control 2 Occipital
29.5


Ctx

Ctx


AD 2 Temporal
22.8
Control 3 Occipital
24.0


Ctx

Ctx


AD 3 Temporal
17.0
Control 4 Occipital
7.4


Ctx

Ctx


AD 4 Temporal
16.8
Control (Path) 1
38.4


Ctx

Occipital Ctx


AD 5 Inf Temporal
50.3
Control (Path) 2
10.3


Ctx

Occipital Ctx


AD 5 Sup
40.6
Control (Path) 3
0.0


Temporal Ctx

Occipital Ctx


AD 6 Inf Temporal
63.7
Control (Path) 4
46.0


Ctx

Occipital Ctx


AD 6 Sup
100.0
Control 1 Parietal
9.2


Temporal Ctx

Ctx


Control 1
9.2
Control 2 Parietal
44.1


Temporal Ctx

Ctx


Control 2
13.3
Control 3 Parietal
21.0


Temporal Ctx

Ctx


Control 3
21.3
Control (Path) 1
20.2


Temporal Ctx

Parietal Ctx


Control 3
14.2
Control (Path) 2
16.7


Temporal Ctx

Parietal Ctx


Control (Path) 1
35.1
Control (Path) 3
0.0


Temporal Ctx

Parietal Ctx


Control (Path) 2
25.3
Control (Path) 4
45.4


Temporal Ctx

Parietal Ctx










[1993]

972





TABLE CFC










General_screening_panel_v1.4











Rel. Exp.

Rel. Exp.



(%) Ag3578,

(%) Ag3578,



Run

Run


Tissue Name
217423081
Tissue Name
217423081













Adipose
8.6
Renal ca. TK-10
19.9


Melanoma*
0.0
Bladder
0.0


Hs688(A).T


Melanoma*
0.0
Gastric ca. (liver met.)
15.3


Hs688(B).T

NCI-N87


Melanoma* M14
0.0
Gastric ca. KATO III
16.4


Melanoma*
0.0
Colon ca. SW-948
22.8


LOXIMVI


Melanoma* SK-
0.0
Colon ca. SW480
5.6


MEL-5


Squamous cell
8.3
Colon ca.* (SW480
42.0


carcinoma SCC-4

met) SW620


Testis Pool
27.4
Colon ca. HT29
2.6


Prostate ca.* (bone
11.0
Colon ca. HCT-116
39.2


met) PC-3


Prostate Pool
0.0
Colon ca. CaCo-2
13.5


Placenta
15.3
Colon cancer tissue
4.8


Uterus Pool
0.0
Colon ca. SW1116
0.0


Ovarian ca.
0.0
Colon ca. Colo-205
4.2


OVCAR-3


Ovarian ca. SK-
14.4
Colon ca. SW-48
9.3


OV-3


Ovarian ca.
8.8
Colon Pool
27.5


OVCAR-4


Ovarian ca.
16.6
Small Intestine Pool
11.2


OVCAR-5


Ovarian ca.
13.0
Stomach Pool
11.3


IGROV-1


Ovarian ca.
4.3
Bone Marrow Pool
8.7


OVCAR-8


Ovary
0.0
Fetal Heart
17.7


Breast ca. MCF-7
0.0
Heart Pool
9.9


Breast ca. MDA-
5.7
Lymph Node Pool
22.4


MB-231


Breast ca. BT 549
47.3
Fetal Skeletal Muscle
10.2


Breast ca. T47D
8.0
Skeletal Muscle Pool
100.0


Breast ca. MDA-N
0.0
Spleen Pool
0.0


Breast Pool
7.6
Thymus Pool
3.5


Trachea
0.0
CNS cancer
0.0




(glio/astro) U87-MG


Lung
3.1
CNS cancer
8.1




(glio/astro) U-118-MG


Fetal Lung
7.1
CNS cancer
22.4




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.0
CNS cancer (astro)
8.2




SF-539


Lung ca. LX-1
49.7
CNS cancer (astro)
25.2




SNB-75


Lung ca. NCI-H146
0.0
CNS cancer (glio)
10.1




SNB-19


Lung ca. SHP-77
0.0
CNS cancer (glio) SF-
24.5




295


Lung ca. A549
0.0
Brain (Amygdala)
7.8




Pool


Lung ca. NCI-H526
0.0
Brain (cerebellum)
20.3


Lung ca. NCI-H23
11.9
Brain (fetal)
18.7


Lung ca. NCI-H460
2.7
Brain (Hippocampus)
14.9




Pool


Lung ca. HOP-62
10.9
Cerebral Cortex Pool
26.2


Lung ca. NCI-H522
0.0
Brain (Substantia
35.4




nigra) Pool


Liver
0.0
Brain (Thalamus) Pool
19.1


Fetal Liver
0.0
Brain (whole)
17.3


Liver ca. HepG2
3.2
Spinal Cord Pool
9.2


Kidney Pool
21.5
Adrenal Gland
3.7


Fetal Kidney
21.2
Pituitary gland Pool
0.0


Renal ca. 786-0
11.7
Salivary Gland
0.0


Renal ca. A498
9.2
Thyroid (female)
6.7


Renal ca. ACHN
11.5
Pancreatic ca.
48.3




CAPAN2


Renal ca. UO-31
10.3
Pancreas Pool
5.5










[1994] CNS_neurodegeneration_v1.0 Summary: Ag3578 This panel confirms the expression of the CG59764-01 gene at low levels in the brain in an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.


[1995] General_screening_panel_v1.4 Summary: Ag3578 Highest expression of the CG59764-01 gene is detected in sample derived from skeletal muscle (CT=31.2). Thus expression of this gene can be used to distinguish skeletal muscle sample from other samples used in this panel. This gene is also expressed at low but significant levels in heart and adipose. Thus, this gene product may be useful in the treatment of metabolic disorders that involve these tissues, including obesity.


[1996] Significant expression of this gene is also associated with samples derived from breast cancer, pancreatic cancer, colon cancer and lung cancer cell lines. Therefore, therapeutic modulation of the activity of this gene or its protein product might be beneficial in the treatment of these cancers.


[1997] In addition, this gene is expressed at low levels throughout the CNS, including in amygdala, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. The CG59764-01 gene encodes a homologue of ferritin heavy chain protein (H-feritin). It has been hypothesized that the up-regulation of the H-ferritin mRNA is part of a mechanism protecting the hippocampus, a seizure-prone area, against a possible overactivation during absence seizures (Lakaye et al., 2000). Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of seizure disorders, such as epilepsy. Furthermore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, schizophrenia and depression.



REFERENCES

[1998] 1. Lakaye B, de Borman B, Minet A, Arckens L, Vergnes M, Marescaux C, Grisar T. (2000) Increased expression of mRNA encoding ferritin heavy chain in brain structures of a rat model of absence epilepsy. Exp Neurol 162(1):112-20.


[1999] Panel 4.1D Summary: Ag3578 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[2000] CG. CG59710-01: P14


[2001] Expression of gene CG59710-01 was assessed using the primer-probe set Ag3512, described in Table CGA. Results of the RTQ-PCR runs are shown in Tables CGB and CGC.


[2002] Table CGA. Probe Name Ag3512
973TABLE CGAProbe Name Ag3512StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-ctttgttctccagcacatctg-3′21211662ProbeTET-5′-ctacatcatggccgagatctgcaatg-3′-TAMRA26232663Reverse5′-cctcgcatytttaggatctg-3′20290664


[2003]

974





TABLE CGB










CNS_neurodegeneration_v1.0













Rel. Exp.



Rel. Exp. (%)

(%) Ag3512,



Ag3512, Run

Run


Tissue Name
211004862
Tissue Name
211004862













AD 1 Hippo
23.0
Control (Path) 3
7.2




Temporal Ctx


AD 2 Hippo
31.2
Control (Path) 4
37.1




Temporal Ctx


AD 3 Hippo
9.8
AD 1 Occipital
20.0




Ctx


AD 4 Hippo
10.0
AD 2 Occipital
0.0




Ctx (Missing)


AD 5 Hippo
85.9
AD 3 Occipital
9.0




Ctx


AD 6 Hippo
56.6
AD 4 Occipital
21.3




Ctx


Control 2 Hippo
41.5
AD 5 Occipital
15.2




Ctx


Control 4 Hippo
21.6
AD 6 Occipital
49.0




Ctx


Control (Path) 3
12.5
Control 1 Occipital
6.0


Hippo

Ctx


AD 1 Temporal Ctx
31.9
Control 2 Occipital
77.4




Ctx


AD 2 Temporal Ctx
41.2
Control 3 Occipital
22.1




Ctx


AD 3 Temporal Ctx
11.3
Control 4 Occipital
9.8




Ctx


AD 4 Temporal Ctx
21.0
Control (Path) 1
77.9




Occipital Ctx


AD 5 Inf Temporal
100.0
Control (Path) 2
12.6


Ctx

Occipital Ctx


AD 5 SupTemporal
42.6
Control (Path) 3
5.4


Ctx

Occipital Ctx


AD 6 Inf Temporal
35.1
Control (Path) 4
21.6


Ctx

Occipital Ctx


AD 6 Sup Temporal
56.6
Control 1 Parietal
11.4


Ctx

Ctx


Control 1 Temporal
10.1
Control 2 Parietal
52.5


Ctx

Ctx


Control 2 Temporal
53.2
Control 3 Parietal
21.5


Ctx

Ctx


Control 3 Temporal
17.2
Control (Path) 1
68.8


Ctx

Parietal Ctx


Control 4 Temporal
15.9
Control (Path) 2
29.7


Ctx

Parietal Ctx


Control (Path) 1
55.1
Control (Path) 3
10.2


Temporal Ctx

Parietal Ctx


Control (Path) 2
39.5
Control (Path) 4
48.3


Temporal Ctx

Parietal Ctx










[2004]

975





TABLE CGC










General_screening_panel_v1.4











Rel. Exp.

Rel. Exp.



(%) Ag3512,

(%) Ag3512,



Run

Run


Tissue Name
217240776
Tissue Name
217240776













Adipose
3.3
Renal ca. TK-10
21.8


Melanoma*
9.7
Bladder
5.5


Hs688(A).T


Melanoma*
10.5
Gastric ca. (liver met.)
37.1


Hs688(B).T

NCI-N87


Melanoma* M14
26.4
Gastric ca. KATO III
48.6


Melanoma*
35.4
Colon ca. SW-948
7.2


LOXIMVI


Melanoma* SK-
14.4
Colon ca. SW480
62.4


MEL-5


Squamous cell
14.9
Colon ca.* (SW480
29.7


carcinoma SCC-4

met) SW620


Testis Pool
6.7
Colon ca. HT29
14.6


Prostate ca.* (bone
17.2
Colon ca. HCT-116
24.1


met) PC-3


Prostate Pool
4.8
Colon ca. CaCo-2
46.0


Placenta
4.4
Colon cancer tissue
13.9


Uterus Pool
3.1
Colon ca. SW1116
2.1


Ovarian ca.
20.0
Colon ca. Colo-205
10.8


OVCAR-3


Ovarian ca. SK-
31.6
Colon ca. SW-48
11.9


OV-3


Ovarian ca.
19.6
Colon Pool
13.4


OVCAR-4


Ovarian ca.
30.8
Small Intestine Pool
7.0


OVCAR-5


Ovarian ca.
10.2
Stomach Pool
4.0


IGROV-1


Ovarian ca.
14.0
Bone Marrow Pool
2.4


OVCAR-8


Ovary
3.6
Fetal Heart
3.3


Breast ca. MCF-7
18.2
Heart Pool
4.1


Breast ca. MDA-
33.7
Lymph Node Pool
7.5


MB-231


Breast ca. BT 549
24.8
Fetal Skeletal Muscle
1.8


Breast ca. T47D
100.0
Skeletal Muscle Pool
6.3


Breast ca. MDA-N
24.8
Spleen Pool
10.8


Breast Pool
7.3
Thymus Pool
5.9


Trachea
2.8
CNS cancer
33.7




(glio/astro) U87-MG


Lung
3.1
CNS cancer
30.1




(glio/astro) U-118-MG


Fetal Lung
7.0
CNS cancer
13.3




(neuro; met) SK-N-AS


Lung ca. NCI-N417
7.3
CNS cancer (astro)
16.2




SF-539


Lung ca. LX-1
17.6
CNS cancer (astro)
46.3




SNB-75


Lung ca. NCI-H146
13.1
CNS cancer (glio)
10.6




SNB-19


Lung ca. SHP-77
21.0
CNS cancer (glio) SF-
27.5




295


Lung ca. A549
25.7
Brain (Amygdala)
4.1




Pool


Lung ca. NCI-H526
15.0
Brain (cerebellum)
6.7


Lung ca. NCI-H23
30.8
Brain (fetal)
6.7


Lung ca. NCI-H460
9.3
Brain (Hippocampus)
4.4




Pool


Lung ca. HOP-62
6.7
Cerebral Cortex Pool
6.3


Lung ca. NCI-H522
15.2
Brain (Substantia
6.1




nigra) Pool


Liver
1.3
Brain (Thalamus) Pool
5.6


Fetal Liver
7.7
Brain (whole)
4.7


Liver ca. HepG2
11.2
Spinal Cord Pool
4.5


Kidney Pool
12.9
Adrenal Gland
3.3


Fetal Kidney
4.2
Pituitary gland Pool
2.6


Renal ca. 786-0
11.8
Salivary Gland
2.5


Renal ca. A498
6.1
Thyroid (female)
3.5


Renal ca. ACHN
10.5
Pancreatic ca.
15.3




CAPAN2


Renal ca. UO-31
18.2
Pancreas Pool
7.6










[2005] CNS_neurodegeneration_v1.0 Summary: Ag3512 This panel confirms the expression of the CG59710-01 gene at low levels in the brain in an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. However, as seen in panel 1.4, this gene is expressed at low levels throughout the CNS, including in amygdala, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, this gene may play a role in other central nervous system disorders such as Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[2006] General_screening_panel_v1.4 Summary: Ag3512 Highest expression of the CG59710-01 gene is detected in a sample derived from a breast cancer cell line (CT=25.3). Therefore, expression of this gene could be used in distinguishing this sample from other samples in the panel. Overall, expression of this gene appears to be associated with the cancer cell lines suggesting a role for this gene product in cellular growth and proliferation. Specifically, significant expression of this gene is associated with CNS cancer, colon cancer, gastric cancer, renal cancer, lung cancer, breast cancer, ovarian cancer, and melanoma cancer cell lines. Therefore, therapeutic modulation of the activity of this gene or its protein product might be beneficial in the treatment of these cancers.


[2007] Panel 4.1D Summary: Ag3512 Results from one experiment with the CG59710-01 gene are not included. The amp plot indicates that there were experimental difficulties with this run.


[2008] CH. CG59754-02 and CG59754-01: Down Syndrome Cell Adhesion Molecule


[2009] Expression of gene CG59754-02 and variant CG59754-01 was assessed using the primer-probe set Ag1305, described in Table CHA.


[2010] Table CHA. Probe Name Ag1305
976TABLE CHAProbe Name Ag1305StartSEQ IDPrimersSequencesLengthPositionNO:Forward5-′-gtgagcattgtgtctccagaa-3′21291665ProbeTET-5′-tttattacctaccacggcgggctgta-3′-TAMRA26321666Reverse5′-tcctccttctgtacgtcagaga-3′22349667


[2011] Panel 4D Summary: Ag1305 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[2012] CI. CG59800-01: Heparan Sulfate D-Glucosaminyl 3-O-Sulfotransferase-3B


[2013] Expression of gene CG59800-01 was assessed using the primer-probe set Ag3589, described in Table CIA.


[2014] Table CIA. Probe Name Ag3589
977TABLE CIAProbe Name Ag3589StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-tacatacctgccctgtccatac-3′2288668ProbeTET-5′-ctacatacctgccccgtccatacctg-3′-TAMRA26117669Reverse5′-gtatggacggggcaggtat-3′19121670


[2015] Results from Panels CNS_neurodegeneration_v1.0, 1.4, 2.2, and 4.1D are not included. The amp plots corresponding to these runs suggest that there were experimental difficulties with these runs.


[2016] CJ. CG59761-01: AXIN 1 (Axis Inhibition Protein 1) (Haxin)—Isoform1, Submitted to Study DDSMT on Mar. 21, 2001 by Cmiller; Clone Status=FIS; Novelty=Novel; ORF Start=97, ORF Stop=2833, Frame=1; 2949 bp.


[2017] Expression of gene CG59761-01 was assessed using the primer-probe set Ag3577, described in Table CJA. Results of the RTQ-PCR runs are shown in Tables CJB, CJC and CJD.


[2018] Table CJA. Probe Name Ag3577
978TABLE CJAProbe Name Ag3577StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-atacttgaagtgggctgagtca-3′22486671ProbeTET-5′-cattccctgctggatgaccaagatg-3′-TAMRA25511672Reverse5′-aggaaagtcctgaacaggctta-3′22539673


[2019]

979





TABLE CJB










CNS_neurodegeneration_v1.0













Rel. Exp.



Rel. Exp. (%)

(%) Ag3577,



Ag3577, Run

Run


Tissue Name
210642177
Tissue Name
210642177













AD 1 Hippo
26.1
Control (Path) 3
7.5




Temporal Ctx


AD 2 Hippo
20.6
Control (Path) 4
26.8




Temporal Ctx


AD 3 Hippo
10.8
AD 1 Occipital
23.5




Ctx


AD 4 Hippo
9.1
AD 2 Occipital
0.0




Ctx (Missing)


AD 5 hippo
86.5
AD 3 Occipital
12.3




Ctx


AD 6 Hippo
48.3
AD 4 Occipital
18.9




Ctx


Control 2 Hippo
21.8
AD 5 Occipital
24.3




Ctx


Control 4 Hippo
16.6
AD 6 Occipital
34.4




Ctx


Control (Path) 3
4.7
Control 1 Occipital
6.2


Hippo

Ctx


AD 1 Temporal Ctx
25.7
Control 2 Occipital
57.4




Ctx


AD 2 Temporal Ctx
28.3
Control 3 Occipital
13.4




Ctx


AD 3 Temporal Ctx
14.5
Control 4 Occipital
8.7




Ctx


AD 4 Temporal Ctx
19.8
Control (Path) 1
62.4




Occipital Ctx


AD 5 Inf Temporal
100.0
Control (Path) 2
10.5


Ctx

Occipital Ctx


AD 5 SupTemporal
44.1
Control (Path) 3
5.3


Ctx

Occipital Ctx


AD 6 Inf Temporal
48.3
Control (Path) 4
20.4


Ctx

Occipital Ctx


AD 6 Sup Temporal
47.0
Control 1 Parietal
15.9


Ctx

Ctx


Control 1 Temporal
11.6
Control 2 Parietal
54.3


Ctx

Ctx


Control 2 Temporal
35.1
Control 3 Parietal
15.5


Ctx

Ctx


Control 3 Temporal
14.6
Control (Path) 1
43.5


Ctx

Parietal Ctx


Control 4 Temporal
12.9
Control (Path) 2
21.3


Ctx

Parietal Ctx


Control (Path) 1
47.0
Control (Path) 3
7.0


Temporal Ctx

Parietal Ctx


Control (Path) 2
28.5
Control (Path) 4
39.0


Temporal Ctx

Parietal Ctx










[2020]

980





TABLE CJC










General_screening_panel_v1.4











Rel. Exp.

Rel. Exp.



(%) Ag3577,

(%) Ag3577,



Run

Run


Tissue Name
217343282
Tissue Name
217343282













Adipose
2.8
Renal ca. TK-10
35.4


Melanoma*
13.9
Bladder
13.3


Hs688(A).T


Melanoma*
13.7
Gastric ca. (liver met.)
70.7


Hs688(B).T

NCI-N87


Melanoma* M14
28.5
Gastric ca. KATO III
100.0


Melanoma*
21.2
Colon ca. SW-948
15.0


LOXIMVI


Melanoma* SK-
24.3
Colon ca. SW480
43.5


MEL-5


Squamous cell
23.2
Colon ca.* (SW480
47.6


carcinoma SCC-4

met) SW620


Testis Pool
6.4
Colon ca. HT29
26.2


Prostate ca.* (bone
32.3
Colon ca. HCT-116
27.2


met) PC-3


Prostate Pool
5.1
Colon ca. CaCo-2
35.4


Placenta
6.2
Colon cancer tissue
13.1


Uterus Pool
2.8
Colon ca. SW1116
14.2


Ovarian ca.
12.5
Colon ca. Colo-205
10.1


OVCAR-3


Ovarian ca. SK-
56.6
Colon ca. SW-48
21.8


OV-3


Ovarian ca.
11.4
Colon Pool
10.7


OVCAR-4


Ovarian ca.
42.0
Small Intestine Pool
10.4


OVCAR-5


Ovarian ca.
12.9
Stomach Pool
5.6


IGROV-1


Ovarian ca.
13.1
Bone Marrow Pool
5.2


OVCAR-8


Ovary
7.3
Fetal Heart
3.5


Breast ca. MCF-7
29.3
Heart Pool
4.0


Breast ca. MDA-
32.3
Lymph Node Pool
12.7


MB-231


Breast ca. BT 549
30.1
Fetal Skeletal Muscle
3.6


Breast ca. T47D
75.3
Skeletal Muscle Pool
10.6


Breast ca. MDA-N
21.8
Spleen Pool
7.3


Breast Pool
12.3
Thymus Pool
13.9


Trachea
10.8
CNS cancer
10.7




(glio/astro) U87-MG


Lung
1.8
CNS cancer
42.9




(glio/astro) U-118-MG


Fetal Lung
16.0
CNS cancer
25.3




(neuro; met) SK-N-AS


Lung ca. NCI-N417
7.0
CNS cancer (astro)
6.0




SF-539


Lung ca. LX-1
79.0
CNS cancer (astro)
34.2




SNB-75


Lung ca. NCI-H146
12.3
CNS cancer (glio)
13.8




SNB-19


Lung ca. SHP-77
29.1
CNS cancer (glio) SF-
28.1




295


Lung ca. A549
29.1
Brain (Amygdala)
5.3




Pool


Lung ca. NCI-H526
7.4
Brain (cerebellum)
34.9


Lung ca. NCI-H23
28.3
Brain (fetal)
21.5


Lung ca. NCI-H460
23.3
Brain (Hippocampus)
5.4




Pool


Lung ca. HOP-62
7.8
Cerebral Cortex Pool
6.3


Lung ca. NCI-H522
28.5
Brain (Substantia
6.6




nigra) Pool


Liver
0.9
Brain (Thalamus) Pool
8.1


Fetal Liver
12.5
Brain (whole)
11.6


Liver ca. HepG2
26.8
Spinal Cord Pool
5.1


Kidney Pool
14.1
Adrenal Gland
10.1


Fetal Kidney
7.2
Pituitary gland Pool
0.0


Renal ca. 786-0
13.6
Salivary Gland
5.9


Renal ca. A498
7.9
Thyroid (female)
5.3


Renal ca. ACHN
22.1
Pancreatic ca.
30.8




CAPAN2


Renal ca. UO-31
17.7
Pancreas Pool
13.9










[2021]

981





TABLE CJD










Panel 4.1D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3577, Run

Ag3577, Run


Tissue Name
169851850
Tissue Name
169851850













Secondary Th1 act
50.0
HUVEC IL-1beta
37.9


Secondary Th2 act
57.0
HUVEC IFN gamma
25.5


Secondary Tr1 act
71.2
HUVEC TNF alpha +
35.8




IFN gamma


Secondary Th1 rest
29.5
HUVEC TNF alpha +
36.9




IL4


Secondary Th2 rest
58.2
HUVEC IL-11
14.6


Secondary Tr1 rest
55.1
Lung Microvascular EC
48.0




none


Primary Th1 act
62.9
Lung Microvascular EC
45.7




TNF alpha + IL-1beta


Primary Th2 act
61.6
Microvascular Dermal
27.5




EC none


Primary Tr1 act
60.7
Microvascular Dermal
24.1




EC TNF alpha + IL-1beta


Primary Th1 rest
50.3
Bronchial epithelium
39.2




TNF alpha + IL1beta


Primary Th2 rest
61.1
Small airway epithelium
20.4




none


Primary Tr1 rest
85.3
Small airway epithelium
57.8




TNF alpha + IL-1beta


CD45RA CD4
47.6
Coronery artery SMC rest
13.9


lymphocyte act


CD45RO CD4
58.6
Coronery artery SMC
12.9


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
55.5
Astrocytes rest
16.8


Secondary CD8
51.4
Astrocytes TNF alpha +
18.7


lymphocyte rest

IL-1beta


Secondary CD8
31.0
KU-812 (Basophil) rest
37.1


lymphocyte act


CD4 lymphocyte none
33.2
KU-812 (Basophil)
64.2




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
54.3
CCD1106
48.0


CD95 CH11

(Keratinocytes) none


LAK cells rest
52.1
CCD1106
43.8




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
50.3
Liver cirrhosis
7.5


LAK cells IL-2 + IL-12
47.0
NCI-H292 none
30.6


LAK cells IL-2 + IFN
62.9
NCI-H292 IL-4
60.3


gamma


LAK cells IL-2 + IL-18
61.1
NCI-H292 IL-9
72.2


LAK cells
95.9
NCI-H292 IL-13
57.8


PMA/ionomycin


NK Cells IL-2 rest
100.0
NCI-H292 IFN gamma
85.9


Two Way MLR 3 day
74.7
HPAEC none
23.0


Two Way MLR 5 day
50.7
HPAEC TNF alpha + IL-
33.4




1beta


Two Way MLR 7 day
27.9
Lung fibroblast none
15.3


PBMC rest
58.2
Lung fibroblast TNF
17.4




alpha + IL-1beta


PBMC PWM
46.7
Lung fibroblast IL-4
23.7


PBMC PHA-L
29.9
Lung fibroblast IL-9
29.3


Ramos (B cell) none
39.2
Lung fibroblast IL-13
30.4


Ramos (B cell)
42.6
Lung fibroblast IFN
36.3


ionomycin

gamma


B lymphocytes PWM
31.9
Dermal fibroblast
47.3




CCD1070 rest


B lymphocytes CD40L
49.7
Dermal fibroblast
94.6


and IL-4

CCD1070 TNF alpha


EOL-1 dbcAMP
59.5
Dermal fibroblast
20.6




CCD1070 IL-1beta


EOL-1 dbcAMP
55.1
Dermal fibroblast IFN
25.0


PMA/ionomycin

gamma


Dendritic cells none
47.6
Dermal fibroblast IL-4
34.6


Dendritic cells LPS
41.2
Dermal Fibroblasts rest
22.4


Dendritic cells anti-
62.4
Neutrophils TNFa + LPS
10.2


CD40


Monocytes rest
50.3
Neutrophils rest
28.9


Monocytes LPS
63.7
Colon
20.2


Macrophages rest
46.0
Lung
21.9


Macrophages LPS
27.7
Thymus
57.0


HUVEC none
15.8
Kidney
15.8


HUVEC starved
29.9










[2022] CNS_neurodegeneration_v1.0 Summary: Ag3577 This panel confirms the expression of the CG59671-01 gene at low levels in the brain in an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. As seen in panel 1.4, this gene is expressed at low levels throughout the CNS, including in amygdala, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, this gene may play a role in other central nervous system disorders such as Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[2023] General_screening_panel_v1.4 Summary: Ag3577 Highest expression of the CG59671-01 gene is detected in a gastric cancer cell line sample (CTs=27.3). In addition, significant expression of this gene is associated with clusters of cell lines derived from ovarian cancer, breast cancer, and gastric cancer. Therefore, expression of this gene might be used to differentiate between these samples and other samples on this panel and as a marker for these cancers. The CG59671-01 gene encodes an Axin 1 protein, which is known play an important role in Wnt signalling transduction pathway. The Wnt/Wingless signaling transduction pathway plays an important role in both embryonic development and tumorigenesis. Beta-Catenin, a key component of the Wnt signaling pathway, interacts with the TCF/LEF family of transcription factors and activates transcription of Wnt target genes. A number of proteins such as the tumor suppressor APC and Axin are also involved in the regulation of the Wnt signaling pathway. Furthermore, mutations in APC or beta-catenin have been found to be responsible for the genesis of human cancers (Akiyama T, 2000). Recently, Dahmen et al. (2001) have shown presence of a single somatic point mutation in exon 1 (Pro255Ser) and deletion of seven large of AXIN1 (12%) in 86 medulloblastoma (MB) samples and 11 MB cell lines. Therefore, AXIN1 may play a role as tumor suppressor gene in MBs. Furthermore, therapeutic modulation of the activity of this gene or its protein product might be beneficial in the treatment of these cancers.


[2024] Among tissues with metabolic function, this gene is expressed at moderate to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.


[2025] This gene is also expressed in all regions of the CNS examined. Please see Panel CNS_neurodegeneration_v1.0 for discussion of utility of this gene in the central nervous system.



REFERENCES

[2026] 1. Akiyama T. (2000) Wnt/beta-catenin signaling. Cytokine Growth Factor Rev 11(4):273-82.


[2027] 2. Dahmen R P, Koch A, Denkhaus D, Tonn J C, Sorensen N, Berthold F, Behrens J, Birchmeier W, Wiestler O D, Pietsch T. (2001) Deletions of AXIN1, a component of the WNT/wingless pathway, in sporadic medulloblastomas. Cancer Res Oct. 1, 2001;61(19):7039-43


[2028] Panel 4.1D Summary: Ag3577 Highest expression of the CG59671-01 gene is detected in resting NK Cells IL-2 cells (CTs=28.3). In addition, this gene is expressed at high to moderate levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.


[2029] CK. CG59708-01 and CG59708-02 and CG59708-03: Ubiquitin Carboxyl-Terminal Hydrolase 21


[2030] Expression of gene CG59708-01, full length clone CG59708-03 and variant CG59708-02 was assessed using the primer-probe set Ag3511, described in Table CKA. Results of the RTQ-PCR runs are shown in Tables CKB, CKC and CKD. Please note that CG59708-03 represents a full-length physical clone of the CG59708-01 gene, validating the prediction of the gene sequence.


[2031] Table CKA. Probe Name Ag3511
982TABLE CKAProbe Name Ag3511StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-acccaaaagggtagtagaacga-3′222431674ProbeTET-5′-cccttctggaacagtttgcagataaa-3′-TAMRA262454675Reverse5′-gccaccttcataatgctgatt-3′212503676


[2032]

983





TABLE CKB










CNS_neurodegeneration_v1.0













Rel. Exp.



Rel. Exp. (%)

(%) Ag3511,



Ag3511, Run

Run


Tissue Name
210499621
Tissue Name
210499621













AD 1 Hippo
8.2
Control (Path) 3
4.1




Temporal Ctx


AD 2 Hippo
17.9
Control (Path) 4
32.1




Temporal Ctx


AD 3 Hippo
6.0
AD 1 Occipital Ctx
17.7


AD 4 Hippo
4.1
AD 2 Occipital Ctx
0.0




(Missing)


AD 5 Hippo
87.1
AD 3 Occipital Ctx
3.1


AD 6 Hippo
52.5
AD 4 Occipital Ctx
20.0


Control 2 Hippo
13.0
AD 5 Occipital Ctx
22.4


Control 4 Hippo
6.4
AD 6 Occipital Ctx
21.6


Control (Path) 3
3.4
Control 1 Occipital
2.5


Hippo

Ctx


AD 1 Temporal
15.0
Control 2 Occipital
39.5


Ctx

Ctx


AD 2 Temporal
22.7
Control 3 Occipital
18.6


Ctx

Ctx


AD 3 Temporal
4.5
Control 4 Occipital
3.8


Ctx

Ctx


AD 4 Temporal
20.0
Control (Path) 1
61.6


Ctx

Occipital Ctx


AD 5 Inf Temporal
100.0
Control (Path) 2
10.4


Ctx

Occipital Ctx


AD 5 Sup
36.6
Control (Path) 3
2.4


Temporal Ctx

Occipital Ctx


AD 6 Inf Temporal
46.7
Control (Path) 4
14.1


Ctx

Occipital Ctx


AD 6 Sup
58.6
Control 1 Parietal
5.3


Temporal Ctx

Ctx


Control 1
5.6
Control 2 Parietal
47.0


Temporal Ctx

Ctx


Control 2
20.2
Control 3 Parietal
14.7


Temporal Ctx

Ctx


Control 3
15.8
Control (Path) 1
57.4


Temporal Ctx

Parietal Ctx


Control 3
6.1
Control (Path) 2
27.4


Temporal Ctx

Parietal Ctx


Control (Path) 1
50.0
Control (Path) 3
2.2


Temporal Ctx

Parietal Ctx


Control (Path) 2
33.2
Control (Path) 4
37.1


Temporal Ctx

Parietal Ctx










[2033]

984





TABLE CKC










General_screening_panel_v1.4











Rel. Exp.

Rel. Exp.



(%) Ag3511,

(%) Ag3511,



Run

Run


Tissue Name
217240774
Tissue Name
217240774













Adipose
4.9
Renal ca. TK-10
18.4


Melanoma*
15.9
Bladder
9.3


Hs688(A).T


Melanoma*
12.8
Gastric ca. (liver met.)
24.3


Hs688(B).T

NCI-N87


Melanoma* M14
20.6
Gastric ca. KATO III
100.0


Melanoma*
9.1
Colon ca. SW-948
4.7


LOXIMVI


Melanoma* SK-
26.6
Colon ca. SW480
63.7


MEL-5


Squamous cell
14.3
Colon ca.*(SW480
26.1


carcinoma SCC-4

met) SW620


Testis Pool
6.3
Colon ca. HT29
17.4


Prostate ca.* (bone
43.5
Colon ca. HCT-116
24.3


met) PC-3


Prostate Pool
6.6
Colon ca. CaCo-2
54.7


Placenta
0.7
Colon cancer tissue
6.5


Uterus Pool
4.4
Colon ca. SW1116
4.8


Ovarian ca.
11.7
Colon ca. Colo-205
2.0


OVCAR-3


Ovarian ca. SK-
45.1
Colon ca. SW-48
4.0


OV-3


Ovarian ca.
17.9
Colon Pool
13.0


OVCAR-4


Ovarian ca.
26.1
Small Intestine Pool
14.1


OVCAR-5


Ovarian ca.
12.5
Stomach Pool
7.2


IGROV-1


Ovarian ca.
10.2
Bone Marrow Pool
6.5


OVCAR-8


Ovary
7.5
Fetal Heart
73.2


Breast ca. MCF-7
9.7
Heart Pool
19.1


Breast ca. MDA-
47.0
Lymph Node Pool
14.5


MB-231


Breast ca. BT 549
58.2
Fetal Skeletal Muscle
34.9


Breast ca. T47D
44.1
Skeletal Muscle Pool
45.1


Breast ca. MDA-N
12.9
Spleen Pool
9.8


Breast Pool
15.2
Thymus Pool
13.0


Trachea
7.1
CNS cancer
2.6




(glio/astro) U87-MG


Lung
3.8
CNS cancer
33.4




(glio/astro) U-118-MG


Fetal Lung
27.5
CNS cancer
8.5




(neuro; met) SK-N-AS


Lung ca. NCI-N417
2.5
CNS cancer (astro)
11.6




SF-539


Lung ca. LX-1
24.0
CNS cancer (astro)
31.6




SNB-75


Lung ca. NCI-H146
3.2
CNS cancer (glio)
12.1




SNB-19


Lung ca. SHP-77
13.0
CNS cancer (glio) SF-
40.9




295


Lung ca. A549
18.9
Brain (Amygdala)
4.7




Pool


Lung ca. NCI-H526
20.6
Brain (cerebellum)
12.0


Lung ca. NCI-H23
23.5
Brain (fetal)
10.7


Lung ca. NCI-H460
10.5
Brain (Hippocampus)
3.8




Pool


Lung ca. HOP-62
10.2
Cerebral Cortex Pool
7.5


Lung ca. NCI-H522
21.8
Brain (Substantia
3.2




nigra) Pool


Liver
1.6
Brain (Thalamus) Pool
8.0


Fetal Liver
10.9
Brain (whole)
5.0


Liver ca. HepG2
7.2
Spinal Cord Pool
3.8


Kidney Pool
16.3
Adrenal Gland
5.0


Fetal Kidney
16.3
Pituitary gland Pool
3.0


Renal ca. 786-0
11.3
Salivary Gland
3.1


Renal ca. A498
4.2
Thyroid (female)
3.1


Renal ca. ACHN
10.2
Pancreatic ca.
25.0




CAPAN2


Renal ca. UO-31
17.1
Pancreas Pool
13.0










[2034]

985





TABLE CKD










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3511, Run

Ag3511, Run


Tissue Name
166407112
Tissue Name
166407112













Secondary Th1 act
26.6
HUVEC IL-1beta
14.8


Secondary Th2 act
31.6
HUVEC IFN gamma
16.8


Secondary Tr1 act
33.7
HUVEC TNF alpha +
9.7




IFN gamma


Secondary Th1 rest
22.8
HUVEC TNF alpha +
9.1




IL4


Secondary Th2 rest
17.2
HUVEC IL-11
9.9


Secondary Tr1 rest
20.3
Lung Microvascular EC
13.2




none


Primary Th1 act
10.4
Lung Microvascular EC
8.3




TNF alpha + IL-1beta


Primary Th2 act
17.2
Microvascular Dermal
22.7




EC none


Primary Tr1 act
25.7
Microsvasular Dermal
11.9




EC TNF alpha + IL-1beta


Primary Th1 rest
57.4
Bronchial epithelium
8.0




TNF alpha + IL1beta


Primary Th2 rest
28.1
Small airway epithelium
3.7




none


Primary Tr1 rest
15.6
Small airway epithelium
24.3




TNF alpha + IL-1beta


CD45RA CD4
11.0
Coronery artery SMC rest
11.9


lymphocyte act


CD45RO CD4
28.1
Coronery artery SMC
7.6


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
19.2
Astrocytes rest
10.6


Secondary CD8
15.3
Astrocytes TNF alpha +
12.4


lymphocyte rest

IL-1beta


Secondary CD8
20.3
KU-812 (Basophil) rest
20.2


lymphocyte act


CD4 lymphocyte none
8.4
KU-812 (Basophil)
46.7




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
24.8
CCD1106
12.6


CD95 CH11

(Keratinocytes) none


LAK cells rest
12.2
CCD1106
53.2




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
49.3
Liver cirrhosis
7.7


LAK cells IL-2 + IL-12
27.5
Lupus kidney
9.7


LAK cells IL-2 + IFN
47.6
NCI-H292 none
59.5


gamma


LAK cells IL-2 + IL-18
35.4
NCI-H292 IL-4
100.0


LAK cells
3.6
NCI-H292 IL-9
69.7


PMA/ionomycin


NK Cells IL-2 rest
46.0
NCI-H292 IL-13
46.7


Two Way MLR 3 day
24.7
NCI-H292 IFN gamma
36.6


Two Way MLR 5 day
22.1
HPAEC none
11.8


Two Way MLR 7 day
13.9
HPAEC TNF alpha + IL-
12.9




1beta


PBMC rest
13.0
Lung fibroblast none
13.3


PBMC PWM
17.3
Lung fibroblast TNF
31.9




alpha + IL-1beta


PBMC PHA-L
11.7
Lung fibroblast IL-4
9.6


Ramos (B cell) none
19.8
Lung fibroblast IL-9
7.4


Ramos (B cell)
18.2
Lung fibroblast IL-13
6.3


ionomycin


B lymphocytes PWM
37.1
Lung fibroblast IFN
10.4




gamma


B lymphocytes CD40L
34.6
Dermal fibroblast
23.7


and IL-4

CCD1070 rest


EOL-1 dbcAMP
14.4
Dermal fibroblast
75.8




CCD1070 TNF alpha


EOL-1 dbcAMP
21.6
Dermal fibroblast
18.7


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
10.8
Dermal fibroblast IFN
5.6




gamma


Dendritic cells LPS
13.5
Dermal fibroblast IL-4
11.3


Dendritic cells anti-
14.4
IBD Colitis 2
5.3


CD40


Monocytes rest
11.6
IBD Crohn's
6.0


Monocytes LPS
7.6
Colon
52.9


Macrophages rest
20.3
Lung
9.7


Macrophages LPS
15.0
Thymus
16.3


HUVEC none
16.8
Kidney
19.9


HUVEC starved
29.9










[2035] CNS_neurodegeneration_v1.0 Summary: Ag3511 This panel confirms the expression of CG59708-01 gene at low levels in the brain in an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. However, as seen in panel 1.4, this gene is expressed at low levels throughout the CNS, including in amygdala, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, this gene may play a role in other central nervous system disorders such as Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[2036] General_screening_panel_v1.4 Summary: Ag3511 Highest expression of the CG59708-01 is detected in a gastric cancer cell line sample (CT=27.1). Thus, expression of this gene can be used to distinguish this sample from other samples in this panel. In addition, high levels of expression of this gene are associated with breast cancer, ovarian cancer, and gastric cancer cell lines. Therefore, therapeutic modulation of the activity of this gene or its protein product might be beneficial in the treatment of these cancers.


[2037] Among tissues with metabolic function, this gene is expressed at moderate to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.


[2038] This gene is also expressed at moderate to low levels in all regions of the CNS examined. Please see Panel CNS_neurodegeneration_v1.0 for discussion of utility of this gene in the central nervous system.


[2039] Panel 4D Summary: Ag3511 Highest expression of the CG59708-01 gene is detected in a IL-4 treated NCI-H292 sample (CT=26.4). In addition, this gene is expressed at high to moderate levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.5 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.


[2040] CL. CG59559-01: CPSase-Related


[2041] Expression of gene CG59559-01 was assessed using the primer-probe set Ag3469, described in Table CLA. Results of the RTQ-PCR runs are shown in Tables CLB, CLC and CLD.


[2042] Table CLA. Probe Name Ag3469
986TABLE CLAProbe Name Ag3469StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-tccagtcggatcaattctattg-3′221213677ProbeTET-5′-attcagatgtcccctcatcagcccat-3′-TAMRA261237678Reverse5′-aattgtcttcgacgaagaaacc-3′221266679


[2043]

987





TABLE CLB










CNS_neurodegeneration_v1.0













Rel. Exp.



Rel. Exp. (%)

(%) Ag3469,



Ag3469, Run

Run


Tissue Name
210376662
Tissue Name
210376662













AD 1 Hippo
23.5
Control (Path) 3
13.9




Temporal Ctx


AD 2 Hippo
31.0
Control (Path) 4
35.6




Temporal Ctx


AD 3 Hippo
17.1
AD 1 Occipital Ctx
8.1


AD 4 Hippo
23.0
AD 2 Occipital Ctx
0.0




(Missing)


AD 5 Hippo
21.0
AD 3 Occipital Ctx
2.0


AD 6 Hippo
69.3
AD 4 Occipital Ctx
25.9


Control 2 Hippo
56.6
AD 5 Occipital Ctx
31.9


Control 4 Hippo
52.5
AD 6 Occipital Ctx
10.4


Control (Path) 3
7.5
Control 1 Occipital
3.3


Hippo

Ctx


AD 1 Temporal
39.8
Control 2 Occipital
42.6


Ctx

Ctx


AD 2 Temporal
35.8
Control 3 Occipital
10.7


Ctx

Ctx


AD 3 Temporal
12.2
Control 4 Occipital
17.6


Ctx

Ctx


AD 4 Temporal
30.1
Control (Path) 1
59.0


Ctx

Occipital Ctx


AD 5 Inf Temporal
37.6
Control (Path) 2
14.6


Ctx

Occipital Ctx


AD 5 Sup
33.4
Control (Path) 3
0.0


Temporal Ctx

Occipital Ctx


AD 6 Inf Temporal
52.1
Control (Path) 4
10.6


Ctx

Occipital Ctx


AD 6 Sup
31.0
Control 1 Parietal
9.1


Temporal Ctx

Ctx


Control 1
12.7
Control 2 Parietal
28.5


Temporal Ctx

Ctx


Control 2
31.4
Control 3 Parietal
17.2


Temporal Ctx

Ctx


Control 3
36.3
Control (Path) 1
64.2


Temporal Ctx

Parietal Ctx


Control 3
16.8
Control (Path) 2
25.7


Temporal Ctx

Parietal Ctx


Control (Path) 1
100.0
Control (Path) 3
1.3


Temporal Ctx

Parietal Ctx


Control (Path) 2
62.4
Control (Path) 4
55.9


Temporal Ctx

Parietal Ctx










[2044]

988





TABLE CLC










General_screening_panel_v1.4











Rel. Exp.

Rel. Exp.



(%) Ag3469,

(%) Ag3469,



Run

Run


Tissue Name
217119419
Tissue Name
217119419













Adipose
3.8
Renal ca. TK-10
7.1


Melanoma*
9.2
Bladder
5.7


Hs688(A).T


Melanoma*
4.7
Gastric ca. (liver met.)
4.9


Hs688(B).T

NCI-N87


Melanorna* M14
0.1
Gastric ca. KATO III
1.0


Melanoma*
0.8
Colon ca. SW-948
0.8


LOXIMVI


Melanoma* SK-
2.3
Colon ca. SW480
0.0


MEL-5


Squamous cell
1.9
Colon ca.* (SW480
5.1


carcinoma SCC-4

met) SW620


Testis Pool
5.1
Colon ca. HT29
8.9


Prostate ca.* (bone
3.6
Colon ca. HCT-116
0.7


met) PC-3


Prostate Pool
1.8
Colon ca. CaCo-2
8.1


Placenta
1.4
Colon cancer tissue
8.2


Uterus Pool
2.7
Colon ca. SW1116
0.3


Ovarian ca.
7.9
Colon ca. Colo-205
1.6


OVCAR-3


Ovarian ca. SK-
11.3
Colon ca. SW-48
0.9


OV-3


Ovarian ca.
0.8
Colon Pool
10.4


OVCAR-4


Ovarian ca.
9.2
Small Intestine Pool
3.6


OVCAR-5


Ovarian ca.
5.5
Stomach Pool
2.7


IGROV-1


Ovarian ca.
2.0
Bone Marrow Pool
6.3


OVCAR-8


Ovary
16.7
Fetal Heart
0.9


Breast ca. MCF-7
31.6
Heart Pool
3.8


Breast ca. MDA-
4.0
Lymph Node Pool
11.9


MB-231


Breast ca. BT 549
3.7
Fetal Skeletal Muscle
0.4


Breast ca. T47D
20.9
Skeletal Muscle Pool
0.5


Breast ca. MDA-N
0.1
Spleen Pool
10.7


Breast Pool
11.3
Thymus Pool
7.5


Trachea
3.8
CNS cancer
10.2




(glio/astro) U87-MG


Lung
9.3
CNS cancer
1.3




(glio/astro) U-118-MG


Fetal Lung
3.8
CNS cancer
0.1




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.0
CNS cancer (astro)
3.0




SF-539


Lung ca. LX-1
13.8
CNS cancer (astro)
10.8




SNB-75


Lung ca. NCI-H146
0.1
CNS cancer (glio)
4.9




SNB-19


Lung ca. SHP-77
6.0
CNS cancer (glio) SF-
21.0




295


Lung ca. A549
100.0
Brain (Amygdala)
1.1




Pool


Lung ca. NCI-H526
0.0
Brain (cerebellum)
2.0


Lung ca. NCI-H23
0.1
Brain (fetal)
1.2


Lung ca. NCI-H460
8.9
Brain (Hippocampus)
1.1




Pool


Lung ca. HOP-62
45.4
Cerabral Cortex Pool
1.2


Lung ca. NCI-H522
4.2
Brain (Substantia
1.3




nigra) Pool


Liver
0.6
Brain (Thalamus) Pool
1.2


Fetal Liver
1.8
Brain (whole)
1.1


Liver ca. HepG2
1.5
Spinal Cord Pool
1.9


Kidney Pool
8.8
Adrenal Gland
26.8


Fetal Kidney
3.7
Pituitary gland Pool
0.5


Renal ca. 786-0
3.9
Salivary Gland
1.3


Renal ca. A498
10.5
Thyroid (female)
0.7


Renal ca. ACHN
6.2
Pancreatic ca.
20.2




CAPAN2


Renal ca. UO-31
6.3
Pancreas Pool
9.6










[2045]

989





TABLE CLD










Panel 4.1D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3469, Run

Ag3469, Run


Tissue Name
169839390
Tissue Name
169839390













Secondary Th1 act
19.2
HUVEC IL-1beta
1.3


Secondary Th2 act
25.2
HUVEC IFN gamma
6.2


Secondary Tr1 act
14.4
HUVEC TNF alpha +
1.3




IFN gamma


Secondary Th1 rest
26.1
HUVEC TNF alpha +
1.1




IL4


Secondary Th2 rest
46.3
HUVEC IL-11
1.1


Secondary Tr1 rest
36.6
Lung Microvascular EC
0.7




none


Primary Th1 act
13.6
Lung Microvascular EC
0.4




TNF alpha + IL-1beta


Primary Th2 act
27.7
Microvascular Dermal
0.1




EC none


Primary Tr1 act
15.2
Microsvasular Dermal
0.0




EC TNF alpha + IL-1beta


Primary Th1 rest
46.0
Bronchial epithelium
5.8




TNF alpha + IL1beta


Primary Th2 rest
44.4
Small airway epithelium
2.0




none


Primary Tr1 rest
45.1
Small airway epithelium
6.9




TNF alpha + IL-1beta


CD45RA CD4
25.2
Coronery artery SMC rest
3.1


lymphocyte act


CD45RO CD4
67.8
Coronery artery SMC
3.4


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
59.5
Astrocytes rest
1.4


Secondary CD8
47.0
Astrocytes TNF alpha +
3.2


lymphocyte rest

IL-1beta


Secondary CD8
38.4
KU-812 (Basophil) rest
3.0


lymphocyte act


CD4 lymphocyte none
61.1
KU-812 (Basophil)
6.4




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
27.2
CCD1106
3.8


CD95 CH11

(Keratinocytes) none


LAK cells rest
50.7
CCD1106
5.2




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
36.9
Liver cirrhosis
3.0


LAK cells IL-2 + IL-12
49.0
NCI-H292 none
5.0


LAK cells IL-2 + IFN
59.5
NCI-H292 IL-4
5.5


gamma


LAK cells IL-2 + IL-18
58.2
NCI-H292 IL-9
6.8


LAK cells
65.5
NCI-H292 IL-13
6.7


PMA/ionomycin


NK Cells IL-2 rest
47.0
NCI-H292 IFN gamma
8.0


Two Way MLR 3 day
54.0
HPAEC none
2.7


Two Way MLR 5 day
25.2
HPAEC TNF alpha + IL-
3.3




1beta


Two Way MLR 7 day
42.6
Lung fibroblast none
1.5


PBMC rest
23.5
Lung fibroblast TNF
1.1




alpha + IL-1beta


PBMC PWM
37.4
Lung fibroblast IL-4
0.7


PBMC PHA-L
59.5
Lung fibroblast IL-9
3.1


Ramos (B cell) none
1.8
Lung fibroblast IL-13
0.7


Ramos (B cell)
2.5
Lung fibroblast IFN
0.3


ionomycin

gamma


B lymphocytes PWM
26.8
Dermal fibroblast
7.7




CCD1070 rest


B lymphocytes CD40L
100.0
Dermal fibroblast
36.9


and IL-4

CCD1070 TNF alpha


EOL-1 dbcAMP
2.7
Dermal fibroblast
5.5




CCD1070 IL-1beta


EOL-1 dbcAMP
0.5
Dermal fibroblast IFN
0.7


PMA/ionomycin

gamma


Dendritic cells none
10.4
Dermal fibroblast IL-4
3.7


Dendritic cells LPS
3.2
Dermal Fibroblasts rest
0.2


Dendritic cells anti-
4.2
Neutrophils TNFa + LPS
0.8


CD40


Monocytes rest
1.7
Neutrophils rest
3.2


Monocytes LPS
2.6
Colon
4.4


Macrophages rest
5.6
Lung
5.0


Macrophages LPS
2.6
Thymus
6.9


HUVEC none
0.7
Kidney
2.0


HUVEC starved
1.6










[2046] CNS_neurodegeneration_v1.0 Summary: Ag3469 This panel confirms the expression of the CG59559-01 gene at low levels in the brain in an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. However, as seen in panel 1.4, this gene is expressed at low levels throughout the CNS, including in amygdala, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, this gene may play a role in other central nervous system disorders such as Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[2047] General_screening_panel_v1.4 Summary: Ag3469 Highest expression of the CG59559-01 gene is detected in sample derived from a lung cancer cell line (CT=25.6). Thus, expression of this gene can be used to distinguish this sample from other samples used in this panel. Furthermore, significant expression of this gene is associated with pancreatic cancer, CNS cancer and breast cancer cell lines. Therefore, therapeutic modulation of the activity of this gene or its protein product might be beneficial in the treatment of these cancers.


[2048] Among tissues with metabolic function, this gene is expressed in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.


[2049] This gene is also expressed at low but significant levels in all regions of the CNS examined. Please see Panel CNS_neurodegeneration_v1.0 for discussion of utility of this gene in the central nervous system.


[2050] Panel 4.1D Summary: Ag3469 Highest expression of the CG59559-01 gene is detected in sample derived CD40L and IL-4 treated B lymphocytes (CT=27.2). Fur5hermore, this gene is expressed at significant levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.


[2051] CM. CG59669-01: Carbonyl Reductase


[2052] Expression of gene CG59669-01 was assessed using the primer-probe set Ag3505, described in Table CMA.


[2053] Table CMA. Probe Name Ag3505
990TABLE CMAProbe Name Ag3505SEQ IDPrimersSequencesLengthStart PositionNO:Forward5′-ccgggtcccagaatctagt-3′194680ProbeTET-5′-cctacgccacggttttgaccacg-3′-TAMRA2323681Reverse5′-gacacacggaccacctgat-3′1974682


[2054] CNS_neurodegeneration_v1.0 Summary: Ag3505 Expression of the CG59669-01 gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[2055] General_screening_panel_v1.4 Summary: Ag3505 Results from one experiment with the CG59669-01 gene are not included. The amp plot indicates that there were experimental difficulties with this run.


[2056] Panel 4.1D Summary: Ag3505 Expression of the CG59669-01 gene is low/undetectable (CTs>35) across all of the samples on this panel due to a probable probe or chemistry failure (data not shown).


[2057] Panel 5 Islet Summary: Ag3505 Expression of the CG59669-01 gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[2058] CN. CG59679-01: Carbonyl Reductase


[2059] Expression of gene CG59679-01 was assessed using the primer-probe set Ag3507, described in Table CNA.


[2060] Table CNA. Probe Name Ag3507
991TABLE CNAProbe Name Ag3507StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-gactggagctaataagggcatt-3′22130683ProbeTET-5′-tcgtgacctgtgtcagcaattctcag-3′-TAMRA26166684Reverse5′-gtgcagtgagcaccacatc-3′19194685


[2061] CNS_neurodegeneration_v1.0 Summary: Ag3507 Expression of the CG59679-01 gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[2062] General_screening_panel_v1.4 Summary: Ag3507 Expression of the CG59679-01 gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[2063] Panel 4.1D Summary: Ag3507 Expression of the CG59679-01 gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown). The data suggest that there may have been experimental difficulties with this run.


[2064] Panel 5 Islet Summary: Ag3507 Expression of CG59679-01 gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[2065] CO. CG59644-01: Putative Protein Phosphatase


[2066] Expression of gene CG59644-01 was assessed using the primer-probe set Ag3503, described in Table COA. Results of the RTQ-PCR runs are shown in Tables COB, COC and COD.


[2067] Table COA. Probe Name Ag3503
992TABLE COAProbe Name Ag3503StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-tcgtacctagtaatcccattgg-3′22410763ProbeTET-5′-ccacaagctactgtgagttgctgcaa-3′-TAMRA26440764Reverse5′-ctaccgagcaaagggactttat-3′22467765


[2068]

993





TABLE COB










CNS_neurodegeneration_v1.0













Rel. Exp.



Rel. Exp. (%)

(%) Ag3503,



Ag3503, Run

Run


Tissue Name
210938272
Tissue Name
210938272













AD 1 Hippo
22.1
Control (Path) 3
5.7




Temporal Ctx


AD 2 Hippo
29.1
Control (Path) 4
25.3




Temporal Ctx


AD 3 Hippo
10.8
AD 1 Occipital
21.8




Ctx


AD 4 Hippo
9.4
AD 2 Occipital
0.0




Ctx (Missing)


AD 5 hippo
100.0
AD 3 Occipital
8.9




Ctx


AD 6 Hippo
80.7
AD 4 Occipital
22.8




Ctx


Control 2 Hippo
27.0
AD 5 Occipital
26.8




Ctx


Control 4 Hippo
11.4
AD 6 Occipital
56.6




Ctx


Control (Path) 3
11.3
Control 1 Occipital
5.6


Hippo

Ctx


AD 1 Temporal Ctx
18.9
Control 2 Occipital
93.3




Ctx


AD 2 Temporal Ctx
29.5
Control 3 Occipital
15.8




Ctx


AD 3 Temporal Ctx
7.2
Control 4 Occipital
6.1




Ctx


AD 4 Temporal Ctx
19.3
Control (Path) 1
80.1




Occipital Ctx


AD 5 Inf Temporal
73.2
Control (Path) 2
7.5


Ctx

Occipital Ctx


AD 5 Sup Temporal
49.0
Control (Path) 3
5.9


Ctx

Occipital Ctx


AD 6 Inf Temporal
68.8
Control (Path) 4
14.5


Ctx

Occipital Ctx


AD 6 Sup Temporal
66.0
Control 1 Parietal
7.6


Ctx

Ctx


Control 1 Temporal
4.4
Control 2 Parietal
29.1


Ctx

Ctx


Control 2 Temporal
53.2
Control 3 Parietal
26.6


Ctx

Ctx


Control 3 Temporal
9.7
Control (Path) 1
95.9


Ctx

Parietal Ctx


Control 4 Temporal
11.3
Control (Path) 2
22.5


Ctx

Parietal Ctx


Control (Path) 1
48.0
Control (Path) 3
6.8


Temporal Ctx

Parietal Ctx


Control (Path) 2
22.2
Control (Path) 4
49.7


Temporal Ctx

Parietal Ctx










[2069]

994





TABLE COC










General_screening_panel_v1.4











Rel. Exp.

Rel. Exp.



(%) Ag3503,

(%) Ag3503,



Run

Run


Tissue Name
217131685
Tissue Name
217131685













Adipose
12.9
Renal ca. TK-10
26.8


Melanoma*
7.7
Bladder
22.1


Hs688(A).T


Melanoma*
11.0
Gastric ca. (liver met.)
63.7


Hs688(B).T

NCI-N87


Melanoma* M14
25.0
Gastric ca. KATO III
66.0


Melanoma*
25.9
Colon ca. SW-948
16.4


LOXIMVI


Melanoma* SK-
69.3
Colon ca. SW480
37.4


MEL-5


Squamous cell
18.9
Colon ca.* (SW480
24.8


carcinoma SCC-4

met) SW620


Testis Pool
13.0
Colon ca. HT29
13.7


Prostate ca.* (bone
51.8
Colon ca. HCT-116
60.3


met) PC-3


Prostate Pool
6.9
Colon ca. CaCo-2
25.7


Placenta
7.1
Colon cancer tissue
34.9


Uterus Pool
5.9
Colon ca. SW1116
8.2


Ovarian ca.
14.0
Colon ca. Colo-205
9.2


OVCAR-3


Ovarian ca. SK-
90.8
Colon ca. SW-48
5.8


OV-3


Ovarian ca.
12.5
Colon Pool
17.4


OVCAR-4


Ovarian ca.
34.2
Small Intestine Pool
15.7


OVCAR-5


Ovarian ca.
33.0
Stomach Pool
6.6


IGROV-1


Ovarian ca.
17.6
Bone Marrow Pool
6.4


OVCAR-8


Ovary
7.8
Fetal Heart
12.1


Breast ca. MCF-7
15.9
Heart Pool
17.7


Breast ca. MDA-
55.1
Lymph Node Pool
17.6


MB-231


Breast ca. BT 549
19.8
Fetal Skeletal Muscle
4.8


Breast ca. T47D
66.9
Skeletal Muscle Pool
100.0


Breast ca. MDA-N
12.2
Spleen Pool
12.5


Breast Pool
17.6
Thymus Pool
14.2


Trachea
28.7
CNS cancer
42.9




(glio/astro) U87-MG


Lung
3.0
CNS cancer
55.1




(glio/astro) U-118-MG


Fetal Lung
18.8
CNS cancer
30.6




(neuro; met) SK-N-AS


Lung ca. NCI-N417
9.1
CNS cancer (astro)
12.2




SF-539


Lung ca. LX-1
41.2
CNS cancer (astro)
22.4




SNB-75


Lung ca. NCI-H146
7.0
CNS cancer (glio)
36.3




SNB-19


Lung ca. SHP-77
26.8
CNS cancer (glio) SF-
50.7




295


Lung ca. A549
24.8
Brain (Amygdala)
12.4




Pool


Lung ca. NCI-H526
8.0
Brain (cerebellum)
14.6


Lung ca. NCI-H23
26.6
Brain (fetal)
10.2


Lung ca. NCI-H460
29.7
Brain (Hippocampus)
13.8




Pool


Lung ca. HOP-62
8.0
Cerebral Cortex Pool
17.2


Lung ca. NCI-H522
19.9
Brain (Substantia
19.1




nigra) Pool


Liver
2.9
Brain (Thalamus) Pool
18.4


Fetal Liver
10.4
Brain (whole)
15.7


Liver ca. HepG2
14.2
Spinal Cord Pool
10.9


Kidney Pool
23.8
Adrenal Gland
25.7


Fetal Kidney
10.4
Pituitary gland Pool
3.9


Renal ca. 786-0
12.3
Salivary Gland
11.1


Renal ca. A498
3.7
Thyroid (female)
4.4


Renal ca. ACHN
27.9
Pancreatic ca.
15.0




CAPAN2


Renal ca. UO-31
12.0
Pancreas Pool
17.1










[2070]

995





TABLE COD










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3503, Run

Ag3503, Run


Tissue Name
166441943
Tissue Name
166441943













Secondary Th1 act
54.3
HUVEC IL-1beta
20.4


Secondary Th2 act
52.5
HUVEC IFN gamma
14.6


Secondary Tr1 act
61.1
HUVEC TNF alpha +
16.0




IFN gamma


Secondary Th1 rest
34.6
HUVEC TNF alpha +
24.8




IL4


Secondary Th2 rest
20.0
HUVEC IL-11
6.6


Secondary Tr1 rest
23.0
Lung Microvascular EC
12.9




none


Primary Th1 act
39.5
Lung Microvascular EC
17.4




TNF alpha + IL-1beta


Primary Th2 act
59.9
Microvascular Dermal
21.6




EC none


Primary Tr1 act
92.7
Microsvasular Dermal
20.2




EC TNF alpha + IL-1beta


Primary Th1 rest
94.6
Bronchial epithelium
17.7




TNF alpha + IL1beta


Primary Th2 rest
31.4
Small airway epithelium
7.9




none


Primary Tr1 rest
32.8
Small airway epithelium
53.6




TNF alpha + IL-1beta


CD45RA CD4
44.1
Coronery artery SMC rest
7.7


lymphocyte act


CD45RO CD4
65.5
Coronery artery SMC
8.3


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
68.3
Astrocytes rest
11.7


Secondary CD8
68.8
Astrocytes TNF alpha +
21.9


lymphocyte rest

IL-1beta


Secondary CD8
40.1
KU-812 (Basophil) rest
12.1


lymphocyte act


CD4 lymphocyte none
20.9
KU-812 (Basophil)
42.6




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
40.9
CCD1106
21.0


CD95 CH11

(Keratinocytes) none


LAK cells rest
22.7
CCD1106
72.2




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
46.7
Liver cirrhosis
12.8


LAK cells IL-2 + IL-12
38.2
Lupus Kidney
16.7


LAK cells IL-2 + IFN
68.8
NCI-H292 none
33.0


gamma


LAK cells IL-2 + IL-18
57.8
NCI-H292 IL-4
35.1


LAK cells
100.0
NCI-H292 IL-9
35.4


PMA/ionomycin


NK Cells IL-2 rest
32.8
NCI-H292 IL-13
24.8


Two Way MLR 3 day
42.9
NCI-H292 IFN gamma
22.5


Two Way MLR 5 day
39.8
HPAEC none
11.2


Two Way MLR 7 day
33.7
HPAEC TNF alpha + IL-
27.9




1beta


PBMC rest
22.5
Lung fibroblast none
10.6


PBMC PWM
54.0
Lung fibroblast TNF
25.5




alpha + IL-1beta


PBMC PHA-L
20.6
Lung fibroblast IL-4
11.6


Ramos (B cell) none
56.3
Lung fibroblast IL-9
5.4


Ramos (B cell)
38.4
Lung fibroblast IL-13
8.5


ionomycin


B lymphocytes PWM
44.8
Lung fibroblast IFN
11.7




gamma


B lymphocytes CD40L
42.9
Dermal fibroblast
16.4


and IL-4

CCD1070 rest


EOL-1 dbcAMP
18.2
Dermal fibroblast
56.3




CCD1070 TNF alpha


EOL-1 dbcAMP
30.4
Dermal fibroblast
14.4


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
31.2
Dermal fibroblast IFN
14.5




gamma


Dendritic cells LPS
40.9
Dermal fibroblast IL-4
29.1


Dendritic cells anti-
31.2
IBD Colitis 2
13.7


CD40


Monocytes rest
50.0
IBD Crohn's
11.6


Monocytes LPS
31.0
Colon
70.7


Macrophages rest
26.4
Lung
17.1


Macrophages LPS
28.9
Thymus
29.3


HUVEC none
22.2
Kidney
40.1


HUVEC starved
25.3










[2071] CNS_neurodegeneration_v1.0 Summary: Ag3503 This panel confirms the expression of this gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.


[2072] General_screening_panel_v1.4 Summary: Ag3503 Expression of the CG59644-01 gene is highest in adult skeletal muscle (CT=25.5). Interestingly, expression of this gene is much lower in fetal skeletal muscle (CT=29.9), suggesting that expression of this gene may be used to distinguish adult and fetal skeletal muscle.


[2073] The CG59644-01 gene encodes a protein with homology to protein phosphatases. This gene is expressed at high to moderate levels in the majority of samples on this panel. However, expression of this gene appears to be higher in cancer cell lines when compared to normal adult tissues. This observation is consistent with the potential role for this gene product in cell survival and proliferation.


[2074] In addition, this gene is expressed at high levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[2075] Among tissues with metabolic or endocrine function, this gene is expressed at high to moderate levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.


[2076] Panel 4D Summary: Ag3503 This gene is expressed at high to moderate levels in a wide range of cell types of significance in the immune response in health and disease. These cells include T cells, B cells, endothelial cells, macrophages, monocytes, dendritic cells, basophils, eosinophils and peripheral blood mononuclear cells, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.5 and also suggests a role for the gene product in cell survival and proliferation. Therefore, therapeutic modulation of the activity of this gene or its protein product may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis., and osteoarthritis.


[2077] CP. CG59662-01: Cyclophilin


[2078] Expression of gene CG59662-01 was assessed using the primer-probe set Ag3504, described in Table CPA. Results of the RTQ-PCR runs are shown in Tables CPB and CPC.


[2079] Table CPA. Probe Name Ag3504
996TABLE CPAProbe Name Ag3504StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-ggtcaaccacaccatgttctt-3′2122686ProbeTET-5′-cttggaccacgtctcctttgagctg-3′-TAMRA2567687Reverse5′-tctttggaaacttttctgcaaa-3′2292688


[2080] Table CPB. General_screening_panel_v1.4
997TABLE CPBGeneral_screening_panel_v1.4Ref. Exp. (%)Rel. Exp. (%)Ag3504, RunAg3504, RunTissue Name217236170Tissue Name217236170Adipose0.5Renal ca. TK-100.4Melanoma*1.0Bladder0.6Hs688(A).TMelanoma*0.4Gastric ca. (liver met.)4.8Hs688(B).TNCI-N87Melanoma* M14100.0Gastric ca. KATO III14.2Melanoma*3.9Colon ca. SW-9482.3LOXIMVIMelanoma* SK-4.9Colon ca. SW48012.9MEL-5Squamous Cell47.6Colon ca.* (SW4800.3carcinoma SCC-4met) SW620Testis Pool2.7Colon ca. HT293.5Prostate ca.* (bone3.1Colon ca. HCT-1161.1met) PC-3Prostate Pool5.7Colon ca. CaCo-211.6Placenta5.0Colon cancer tissue7.6Uterus Pool2.2Colon ca. SW11161.5Ovarian ca.20.6Colon ca. Colo-20511.7OVCAR-3Ovarian ca. SK-6.3Colon ca. SW-486.2OV-3Ovarian ca.1.5Colon Pool4.7OVCAR-4Ovarian ca.10.2Small Intestine Pool2.5OVCAR-5Ovarian ca.0.6Stomach Pool5.8IGROV-1Ovarian ca.0.7Bone Marrow Pool1.2OVCAR-8Ovary2.2Fetal Heart3.3Breast ca. MCF-72.9Heart Pool2.2Breast ca. MDA-4.0Lymph Node Pool11.8MB-231Breast ca. BT 5495.6Fetal Skeletal Muscle0.9Breast ca. T47D15.0Skeletal Muscle Pool32.3Breast ca. MDA-N17.7Spleen Pool2.0Breast Pool0.9Thymus Pool9.3Trachea2.0CNS cancer1.0(glio/astro) U87-MGLung16.3CNS cancer3.3(glio/astro) U-118-MGFetal Lung42.0CNS cancer6.2(neuro;met) SK-N-ASLung ca. NCI-N4173.6CNS cancer (astro) SF-2.3539Lung ca. LX-10.7CNS cancer (astro)12.7SNB-75Lung ca. NCI-H1465.1CNS cancer (glio)4.1SNB-19Lung ca. SHP-7717.6CNS cancer (glio) SF-0.7295Lung ca. A54919.9Brain (Amygdala) Pool3.3Lung ca. NCI-H5264.3Brain (cerebellum)2.3Lung ca. NCI-H233.3Brain (fetal)0.9Lung ca. NCI-H4603.8Brain (Hippocampus)16.3PoolLung ca. HOP-620.7Cerebral Cortex Pool0.5Lung ca. NCI-H5221.5Brain (Substantia4.6nigra) PoolLiver1.2Brain (Thalamus) Pool9.0Fetal Liver17.2Brain (whole)1.4Liver ca. HepG21.2Spinal Cord Pool11.6Kidney Pool5.1Adrenal Gland0.3Fetal Kidney7.1Pituitary gland Pool3.9Renal ca. 786-01.2Salivary Gland1.2Renal ca. A4982.4Thyroid (female)5.5Renal ca. ACHN1.2Pancreatic ca.0.6CAPAN2Renal ca. UO-312.5Pancreas Pool8.8


[2081] CNS_neurodegeneration_v1.0 Summary: Ag3504 Expression of the CG59662-01 gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[2082] General_screening_panel_v1.4 Summary: Ag3504 The CG59662-01 gene is expressed at low le,vels in the majority of samples on this panel, with highest expression in a melanoma cell line (CT=30). The CG59662-01 gene encodes a protein with homology to cyclophilin, a specific high-affinity binding protein for the immunosuppressant agent cyclosporin A.


[2083] Among tissues with metabolic or endocrine function, this gene is expressed at low levels in pancreas, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes. Interestingly, this gene is expressed at higher levels in fetal liver (CT=32.5) than in adult liver (CT=36.4), suggesting that expression of this gene can be used to distinguish fetal and adult liver.


[2084] In addition, this gene is expressed at low levels in some regions of the central nervous system, including amygdala, hippocampus, substantia nigra, thalamus, and spinal cord. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[2085] Panel 4D Summary: Ag3504 Significant expression of this gene is detected in a liver cirrhosis sample (CT=34.4). Furthermore, expression of this gene is not detected at significant levels in normal adult liver in Panel 1.4, suggesting that its expression is unique to liver cirrhosis. This gene encodes a putative cyclophilin; therefore, small molecule therapeutics could reduce or inhibit fibrosis that occurs in liver cirrhosis. In addition, expression of this putative cyclophilin could also be used for the diagnosis of liver cirrhosis.


[2086] CQ. CG59773-01: Splice Variant Of Myomegalin


[2087] Expression of gene CG59773-01 was assessed using the primer-probe set Ag3580, described in Table CQA. Results of the RTQ-PCR runs are shown in Tables CQB, CQC and CQD.
998TABLE DDAProbe Name Ag3591StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-cactgctccacttttgtcttg-3′211195728ProbeTET-5′-cataaaaggacccacacaggagaaaa-3′-TAMRA261216729Reverse5′-cttttccacattctttgcattc-3′221249730


[2088]

999





TABLE DGD










Panel 4.1D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3635, Run

Ag3635, Run


Tissue Name
169960385
Tissue Name
169960385













Secondary Th1 act
26.1
HUVEC IL-1beta
12.5


Secondary Th2 act
19.1
HUVEC IFN gamma
34.6


Secondary Tr1 act
12.7
HUVEC TNF alpha +
3.2




IFN gamma


Secondary Th1 rest
2.0
HUVEC TNF alpha +
5.3




IL4


Secondary Th2 rest
8.2
HUVEC IL-11
29.3


Secondary Tr1 rest
4.8
Lung Microvascular EC
12.7




none


Primary Th1 act
16.0
Lung Microvascular EC
3.0




TNF alpha + IL-1beta


Primary Th2 act
17.8
Microvascular Dermal
6.0




EC none


Primary Tr1 act
13.1
Microsvasular Dermal
4.3




EC TNF alpha + IL-1beta


Primary Th1 rest
3.4
Bronchial epithelium
12.5




TNF alpha + IL-1beta


Primary Th2 rest
6.3
Small airway epithelium
4.5




none


Primary Tr1 rest
5.4
Small airway epithelium
11.0




TNF alpha + IL-1beta


CD45RA CD4
17.1
Coronery artery SMC rest
20.4


lymphocyte act


CD45RO CD4
44.1
Coronery artery SMC
21.8


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
23.3
Astrocytes rest
6.4


Secondary CD8
42.9
Astrocytes TNF alpha +
9.9


lymphocyte rest

IL-1beta


Secondary CD8
7.4
KU-812 (Basophil) rest
0.2


lymphocyte act


CD4 lymphocyte none
11.5
KU-812 (Basophil)
0.8




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
2.4
CCD1106
11.2


CD95 CH11

(Keratinocytes) none


LAK cells rest
36.3
CCD1106
22.8




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
9.1
Liver cirrhosis
7.4


LAK cells IL-2 + IL-12
22.8
NCI-H292 none
14.3


LAK cells IL-2 + IFN
21.8
NCI-H292 IL-4
20.9


gamma


LAK cells IL-2 + IL-18
21.2
NCI-H292 IL-9
26.1


LAK cells
21.0
NCI-H292 IL-13
25.5


PMA/ionomycin


NK Cells IL-2 rest
8.7
NCI-H292 IFN gamma
13.2


Two Way MLR 3 day
24.8
HPAEC none
32.5


Two Way MLR 5 day
18.7
HPAEC TNF alpha + IL-
14.3




1beta


Two Way MLR 7 day
21.6
Lung fibroblast none
1.3


PBMC rest
23.0
Lung fibroblast TNF
0.8




alpha + IL-1beta


PBMC PWM
71.2
Lung fibroblast IL-4
1.5


PBMC PHA-L
46.7
Lung fibroblast IL-9
2.9


Ramos (B cell) none
1.8
Lung fibroblast IL-13
1.4


Ramos (B cell)
1.5
Lung fibroblast IFN
1.2


ionomycin

gamma


B lymphocytes PWM
49.7
Dermal fibroblast
33.7




CCD1070 rest


B lymphocytes CD40L
68.8
Dermal fibroblast
22.5


and IL-4

CCD1070 TNF alpha


EOL-1 dbcAMP
22.7
Dermal fibroblast
10.1




CCD1070 IL-1beta


EOL-1 dbcAMP
40.3
Dermal fibroblast IFN
6.1


PMA/ionomycin

gamma


Dendritic cells none
54.0
Dermal fibroblast IL-4
10.4


Dendritic cells LPS
73.7
Dermal Fibroblasts rest
9.9


Dendritic cells anti-
100.0
Neutrophils TNFa + LPS
0.8


CD40


Monocytes rest
66.0
Neutrophils rest
2.8


Monocytes LPS
22.4
Colon
6.7


Macrophages rest
86.5
Lung
34.6


Macrophages LPS
13.4
Thymus
51.1


HUVEC none
8.6
Kidney
90.8


HUVEC starved
11.3










[2089]

1000





TABLE CQC










General_screening_panel_v1.4











Rel.

Rel.



Exp.

Exp.



(%)

(%)



Ag3580,

Ag3580,



Run

Run


Tissue Name
217423587
Tissue Name
217423587













Adipose
20.7
Renal ca. TK-10
20.7


Melanoma*
76.8
Bladder
15.7


Hs688(A).T


Melanoma*
38.7
Gastric ca. (liver met.)
50.0


Hs688(B).T

NCI-N87


Melanoma* M14
7.6
Gastric ca. KATO III
13.1


Melanoma*
81.2
Colon ca. SW-948
5.8


LOXIMVI


Melanoma* SK-
14.9
Colon ca. SW480
12.9


MEL-5


Squamous cell
10.2
Colon ca.* (SW480
2.6


carcinoma SCC-4

met) SW620


Testis Pool
4.5
Colon ca. HT29
4.5


Prostate ca.* (bone
29.1
Colon ca. HCT-116
15.0


met) PC-3


Prostate Pool
6.1
Colon ca. CaCo-2
29.7


Placenta
8.2
Colon cancer tissue
8.4


Uterus Pool
7.7
Colon ca. SW1116
2.5


Ovarian ca.
24.0
Colon ca. Colo-205
2.9


OVCAR-3


Ovarian ca.
15.4
Colon ca. SW-48
7.1


SK-OV-3


Ovarian ca.
17.0
Colon Pool
18.8


OVCAR-4


Ovarian ca.
19.8
Small Intestine Pool
18.0


OVCAR-5


Ovarian ca.
15.1
Stomach Pool
7.4


IGROV-1


Ovarian ca.
6.7
Bone Marrow Pool
9.9


OVCAR-8


Ovary
4.4
Fetal Heart
9.0


Breast ca. MCF-7
28.9
Heart Pool
8.2


Breast ca. MDA-
39.8
Lymph Node Pool
22.8


MB-231


Breast ca. BT 549
13.9
Fetal Skeletal Muscle
6.8


Breast ca. T47D
49.0
Skeletal Muscle Pool
22.7


Breast ca. MDA-N
7.6
Spleen Pool
12.1


Breast Pool
9.5
Thymus Pool
19.9


Trachea
15.0
CNS cancer
35.1




(glio/astro)




U87-MG


Lung
4.0
CNS cancer
28.9




(glio/astro)




U-118-MG


Fetal Lung
30.6
CNS cancer
3.4




(neuro; met)




SK-N-AS


Lung ca. NCI-N417
5.4
CNS cancer
13.4




(astro)




SF-539


Lung ca. LX-1
6.6
CNS cancer (astro)
57.4




SNB-75


Lung ca. NCI-H146
15.8
CNS cancer (glio)
9.0




SNB-19


Lung ca. SHP-77
25.9
CNS cancer (glio)
49.7




SF-295


Lung ca. A549
4.2
Brain (Amygdala)
15.9




Pool


Lung ca. NCI-H526
7.6
Brain (cerebellum)
100.0


Lung ca. NCI-H23
50.0
Brain (fetal)
69.3


Lung ca. NCI-H460
4.8
Brain (Hippocampus)
16.0




Pool


Lung ca. HOP-62
24.3
Cerebral Cortex Pool
26.1


Lung ca. NCI-H522
4.5
Brain
22.7




(Substantia nigra)




Pool


Liver
4.9
Brain (Thalamus) Pool
37.4


Fetal Liver
12.0
Brain (whole)
33.4


Liver ca. HepG2
11.1
Spinal Cord Pool
34.4


Kidney Pool
54.0
Adrenal Gland
5.2


Fetal Kidney
40.3
Pituitary gland Pool
9.7


Renal ca. 786-0
13.9
Salivary Gland
3.4


Renal ca. A498
15.0
Thyroid (female)
5.3


Renal ca. ACHN
1.6
Pancreatic ca.
16.4




CAPAN2


Renal ca. UO-31
10.2
Pancreas Pool
17.2










[2090]

1001





TABLE CQD










Panel 4.1D











Rel.

Rel.



Exp.

Exp.



(%)

(%)



Ag3580,

Ag3580,



Run

Run


Tissue Name
169910382
Tissue Name
169910382













Secondary Th1 act
28.3
HUVEC IL-1beta
28.5


Secondary Th2 act
32.8
HUVEC IFN gamma
8.0


Secondary Tr1 act
34.2
HUVEC TNF alpha +
30.1




IFN gamma


Secondary Th1 rest
23.7
HUVEC TNF alpha +
27.2




IL4


Secondary Th2 rest
26.4
HUVEC IL-11
8.8


Secondary Tr1 rest
34.2
Lung Microvascular
42.9




EC none


Primary Th1 act
11.2
Lung Microvascular
33.2




EC TNFalpha +




IL-1beta


Primary Th2 act
10.8
Microvascular Dermal
24.8




EC none


Primary Tr1 act
11.0
Microvascular Dermal
20.7




EC TNFalpha +




IL-1beta


Primary Th1 rest
32.3
Bronchial epithelium
18.6




TNFalpha + IL1beta


Primary Th2 rest
31.2
Small airway
8.2




epithelium none


Primary Tr1 rest
24.1
Small airway
10.7




epithelium




TNFalpha + IL-beta


CD45RA CD4
50.0
Coronery artery
10.7


lymphocyte act

SMC rest


CD45RO CD4
25.5
Coronery artery
15.6


lymphocyte act

SMC TNFalpha +




IL-1beta


CD8 lymphocyte act
18.8
Astrocytes rest
14.1


Secondary CD8
16.3
Astrocytes
13.0


lymphocyte rest

TNFalpha +




IL-1beta


Secondary CD8
16.3
KU-812 (Basophil)
4.0


lynphocyte act

rest


CD4 lymphocyte
22.4
KU-812 (Basophil)
7.8


none

PMA/ionomycin


2ry Th1/Th2/
47.6
CCD1106
24.3


Tr1_anti-

(Keratinocytes)


CD95 CH11

none


LAK cells rest
24.1
CCD1106
26.4




(Keratinocytes)




TNFalpha + IL-1beta


LAK cells IL-2
21.8
Liver cirrhosis
12.0


LAK cells IL-2 +
23.2
NCI-H292 none
9.6


IL-12


LAK cells IL-2 +
29.1
NCI-H292 IL-4
15.5


IFN gamma


LAK cells IL-2 +
32.5
NCI-H292 IL-9
26.2


IL-18


LAK cells
35.8
NCI-H292 IL-13
15.3


PMA/ionomycin


NK Cells IL-2 rest
26.1
NCI-H292 IFN gamma
14.0


Two Way MLR
35.8
HPAEC none
8.2


3 day


Two Way MLR
19.5
HPAEC TNF alpha +
31.9


5 day

IL-1beta


Two Way MLR
46.0
Lung fibroblast none
51.8


7 day


PBMC rest
15.8
Lung fibroblast
44.8




TNF alpha +




IL-1beta


PBMC PWM
16.0
Lung fibroblast IL-4
32.8


PBMC PHA-L
13.3
Lung fibroblast IL-9
51.4


Ramos (B cell) none
16.8
Lung fibroblast IL-13
29.9


Ramos (B cell)
15.9
Lung fibroblast IFN
27.7


ionomycin

gamma


B lymphocytes
14.4
Dermal fibroblast
38.4


PMW

CCD1070 rest


B lymphocytes
16.3
Dermal fibroblast
100.0


CD40L and IL-4

CCD1070 TNF alpha


EOL-1 dbcAMP
5.6
Dermal fibroblast
48.3




CCD1070 IL-1beta


EOL-1 dbcAMP
29.3
Dermal fibroblast IFN
11.0


PMA/ionomycin

gamma


Dendritic cells none
13.6
Dermal fibroblast IL-4
22.7


Dendritic cells LPS
14.4
Dermal Fibroblasts
18.8




rest


Dendritic cells anti-
13.5
Neutrophils TNFa +
1.7


CD40

LPS


Monocytes rest
12.3
Neutrophils rest
2.6


Monocytes LPS
62.9
Colon
15.8


Macrophages rest
18.4
Lung
15.6


Macrophages LPS
15.3
Thymus
21.8


HUVEC none
12.6
Kidney
46.3


HUVEC starved
17.0










[2091] CNS_neurodegeneration_v1.0 Summary: Ag3580 Results from two experiments using the same probe/primer set are in excellent agreement. This panel confirms the expression of this gene at high to moderate levels in the brains of an independent group of individuals. This gene is found to be upregulated in the temporal cortex of Alzheimer's disease patients. Therefore, therapeutic modulation of this gene or its protein product may be used to decrease neuronal death and treat Alzheimer's disease.


[2092] General_screening_panel_v1.4 Summary: Ag3580 The CG59773-01 gene encodes a splice variant of the myomegalin protein, which is a component of the golgi/centrosome and interacts with a cyclic nucleotide phosphodiesterase (ref. 1). Expression of the CG59773-01 gene is highest in the cerebellum (CT=23.8). In addition, this gene is expressed at high levels in all other regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebral cortex, and spinal cord. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[2093] Among tissues with metabolic or endocrine function, this gene is expressed at high to moderate levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.


[2094] This gene is also expressed at very high levels in a number of melanoma cell lines. Therefore, therapeutic modulation of the activity of this gene or its protein product may be of benefit in the treatment of melanoma.



References

[2095] 1. Verde I, Pahlke G, Salanova M, Zhang G, Wang S, Coletti D, Onuffer J, Jin S L, Conti M. Myomegalin is a novel protein of the golgi/centrosome that interacts with a cyclic nucleotide phosphodiesterase. J Biol Chem Apr. 6, 2001;276(14): 11189-98


[2096] Panel 4.1D Summary: Ag3580 This gene is expressed at high to moderate levels in a wide range of cell types of significance in the immune response in health and disease. These cells include T cells, B cells, endothelial cells, macrophages, monocytes, dendritic cells, basophils, eosinophils and peripheral blood mononuclear cells, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.5 and also suggests a role for the gene product in cell survival and proliferation. Therefore, therapeutic modulation of the activity of this gene or its protein product may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.


[2097] CR. CG57460-01: N-Acetyltransferase Camello 2


[2098] Expression of gene CG57460-01 was assessed using the primer-probe set Ag3273, described in Table CRA. Results of the RTQ-PCR runs are shown in Tables CRB, CRC and CRD.
1002TABLE CRAProbe Name Ag3273SEQStartIDPrimersSequencesLengthPositionNO:Forward5′-cgctactactacagccgcaa-3′20205692ProbeTET-5′-gtgatccgcgcctacctggagtg-3′-23226693TAMRAReverse5′-gggcggcttcatgtagtact-3′20281694


[2099]

1003





TABLE CRB










CNS_neurodegeneration_v1.0













Rel. Exp. (%)
Rel. Exp. (%)

Rel. Exp. (%)
Rel. Exp. (%)


Tissue
Ag3273, Run
Ag3273, Run
Tissue
Ag3273, Run
Ag3273, Run


Name
210038591
230512515
Name
210038591
230512515















AD 1 Hippo
15.7
18.6
Control
12.2
12.7





(Path) 3





Temporal





Ctx


AD 2 Hippo
28.9
23.2
Control
40.3
35.4





(Path) 4





Temporal





Ctx


AD 3 Hippo
11.0
11.0
AD 1
20.9
18.8





Occipital





Ctx


AD 4 Hippo
10.2
13.8
AD 2
0.0
0.0





Occipital





Ctx





(Missing)


AD 5 hippo
100.0
100.0
AD 3
15.2
13.1





Occipital





Ctx


AD 6 Hippo
21.8
22.4
AD 4
22.1
23.2





Occipital





Ctx


Control 2
27.0
27.9
AD 5
18.4
18.4


Hippo


Occipital





Ctx


Control 4
22.5
21.8
AD 6
46.3
48.3


Hippo


Occipital





Ctx


Control (Path)
8.4
9.0
Control 1
8.0
11.2


3 Hippo


Occipital





Ctx


AD 1 Temporal
16.5
15.1
Control 2
80.1
82.4


Ctx


Occipital





Ctx


AD 2 Temporal
29.3
26.2
Control 3
26.2
27.2


Ctx


Occipital





Ctx


AD 3 Temporal
10.9
12.9
Control 4
14.8
14.1


Ctx


Occipital





Ctx


AD 4 Temporal
22.5
20.3
Control
70.2
68.8


Ctx


(Path) 1





Occipital





Ctx


AD 5 Inf
57.0
59.5
Control
21.6
20.6


Temporal Ctx


(Path) 2





Occipital





Ctx


AD 5
30.6
26.8
Control
8.8
7.4


Sup Temporal


(Path) 3


Ctx


Occipital





Ctx


AD 6 Inf
27.2
30.1
Control
36.1
34.2


Temporal Ctx


(Path) 4





Occipital





Ctx


AD 6 Sup
34.2
37.4
Control 1
14.1
13.7


Temporal Ctx


Parietal Ctx


Control 1
12.2
11.1
Control 2
33.9
36.9


Temporal Ctx


Parietal Ctx


Control 2
43.2
39.8
Control 3
33.0
28.7


Temporal Ctx


Parietal Ctx


Control 3
16.7
18.3
Control
63.7
67.8


Temporal Ctx


(Path) 1





Parietal Ctx


Control 4
18.3
19.8
Control
30.6
30.4


Temporal Ctx


(Path) 2





Parietal Ctx


Control (Path)
51.4
48.0
Control
8.1
9.7


1 Temporal Ctx


(Path) 3





Parietal Ctx


Control (Path)
39.2
45.7
Control
64.2
59.5


2 Temporal Ctx


(Path) 4





Parietal Ctx










[2100]

1004





TABLE CRC










General_screening_panel_v1.4











Rel.

Rel.



Exp.

Exp.



(%)

(%)



Ag3273,

Ag3273,



Run

Run


Tissue Name
215775405
Tissue Name
215775405













Adipose
7.1
Renal ca. TK-10
4.9


Melanoma*
0.0
Bladder
0.9


Hs688(A).T


Melanoma*
0.0
Gastric ca. (liver met.)
2.4


Hs688(B).T

NCI-N87


Melanoma* M14
17.6
Gastric ca. KATO III
0.0


Melanoma*
0.9
Colon ca. SW-948
0.0


LOXIMVI


Melanoma* SK-
4.2
Colon ca. SW480
2.7


MEL-5


Squamous cell
0.2
Colon ca.* (SW480
1.0


carcinoma SCC-4

met) SW620


Testis Pool
13.5
Colon ca. HT29
0.1


Prostate ca.* (bone
2.7
Colon ca. HCT-116
6.0


met) PC-3


Prostate Pool
0.2
Colon ca. CaCo-2
2.0


Placenta
0.0
Colon cancer tissue
0.6


Uterus Pool
0.0
Colon ca. SW1116
0.4


Ovarian ca.
5.4
Colon ca. Colo-205
0.0


OVCAR-3


Ovarian ca.
6.8
Colon ca. SW-48
0.0


SK-OV-3


Ovarian ca.
1.6
Colon Pool
0.4


OVCAR-4


Ovarian ca.
2.1
Small Intestine Pool
0.1


OVCAR-5


Ovarian ca.
7.7
Stomach Pool
0.3


IGROV-1


Ovarian ca.
9.6
Bone Marrow Pool
0.1


OVCAR-8


Ovary
0.8
Fetal Heart
100.0


Breast ca. MCF-7
1.7
Heart Pool
0.2


Breast ca. MDA-
0.8
Lymph Node Pool
0.0


MB-231


Breast ca. BT 549
7.7
Fetal Skeletal Muscle
0.3


Breast ca. T47D
9.3
Skeletal Muscle Pool
1.3


Breast ca. MDA-N
0.0
Spleen Pool
0.0


Breast Pool
0.4
Thymus Pool
0.4


Trachea
0.2
CNS cancer
0.0




(glio/astro)




U87-MG


Lung
0.0
CNS cancer
0.0




(glio/astro)




U-118-MG


Fetal Lung
0.3
CNS cancer
0.0




(neuro; met)




SK-N-AS


Lung ca. NCI-N417
5.1
CNS cancer
0.2




(astro)




SF-539


Lung ca. LX-1
0.4
CNS cancer (astro)
0.6




SNB-75


Lung ca. NCI-H146
12.2
CNS cancer (glio)
7.1




SNB-19


Lung ca. SHP-77
2.4
CNS cancer (glio)
1.8




SF-295


Lung ca. A549
3.4
Brain (Amygdala)
31.4




Pool


Lung ca. NCI-H526
12.0
Brain (cerebellum)
32.3


Lung ca. NCI-H23
5.8
Brain (fetal)
9.3


Lung ca. NCI-H460
2.3
Brain (Hippocampus)
22.5




Pool


Lung ca. HOP-62
1.0
Cerebral Cortex Pool
40.3


Lung ca. NCI-H522
7.4
Brain
57.4




(Substantia nigra)




Pool


Liver
0.0
Brain (Thalamus) Pool
36.6


Fetal Liver
0.1
Brain (whole)
24.8


Liver ca. HepG2
0.3
Spinal Cord Pool
20.2


Kidney Pool
0.2
Adrenal Gland
0.0


Fetal Kidney
0.7
Pituitary gland Pool
2.2


Renal ca. 786-0
0.2
Salivary Gland
0.2


Renal ca. A498
1.0
Thyroid (female)
1.1


Renal ca. ACHN
4.5
Pancreatic ca.
0.0




CAPAN2


Renal ca. UO-31
3.7
Pancreas Pool
0.6










[2101]

1005





TABLE CRD










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3273, Run

Ag3273, Run


Tissue Name
165338992
Tissue Name
165338992













Secondary Th1 act
1.0
HUVEC IL-1beta
0.0


Secondary Th2 act
2.5
HUVEC IFN gamma
0.0


Secondary Tr1 act
3.7
HUVEC TNF alpha+
0.0




IFN gamma


Secondary Th1 rest
5.0
HUVEC TNF alpha+
0.0




IL4


Secondary Th2 rest
0.9
HUVEC IL-11
0.0


Secondary Th1 rest
6.9
Lung Microvascular EC
0.0




none


Primary Th1 act
6.2
Lung Microvascular EC
0.0




TNFalpha + IL-1beta


Primary Th2 act
5.9
Microvascular Dermal
0.0




EC none


Primary Tr1 act
9.5
Microsvasular Dermal
0.0




EC TNFalpha + IL-1beta


Primary Th1 rest
3.1
Bronchial epithelium
0.0




TNFalpha + IL-1beta


Primary Th2 rest
0.0
Small airway epithelium
2.9




none


Primary Tr1 rest
0.0
Small airway epithelium
0.0




TNFalpha + IL-1beta


CD45RA CD4
0.0
Coronery artery SMC rest
1.8


lymphocyte act


CD45RO CD4
0.0
Coronery artery SMC
0.0


lymphocyte act

TNFalpha + IL-1beta


CD8 lymphocyte act
0.0
Astrocytes rest
16.5


Secondary CD8
0.0
Astrocytes TNFalpha +
10.4


lymphocyte rest

IL-1beta


Secondary CD8
0.0
KU-812 (Basophil) rest
0.0


lymphocyte act


CD4 lymphocyte none
0.0
KU-812 (Basophil)
0.0




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
19.1
CCD1106
0.0


CD95 CH11

(Keratinocytes) none




CCD1106


LAK cells rest
0.0
(Keratinocytes)
0.0




TNFalpha + IL-1beta


LAK cells IL-2
1.2
liver cirrhosis
12.7


LAK cells IL-2 + IL-12
2.5
Lupus kidney
3.9


LAK cells IL-2 + IFN
4.1
NCI-H292 none
10.8


gamma


LAK cells IL-2 + IL-18
0.0
NCI-H292 IL-4
23.2


LAK cells
0.0
NCI-H292 IL-9
22.4


PMA/ionomycin


NK Cells IL-2 rest
0.0
NCI-H292 IL-13
10.3


Two Way MLR 3 day
1.1
NCI-H292 IFN gamma
18.0


Two Way MLR 5 day
0.0
AHPAEC none
0.0


Two Way MLR 7 day
0.0
HPAEC TNF alpha + IL-
0.0




1 beta


PBMC rest
0.0
Lung fibroblast none
1.9


PBMC PWM
1.2
Lung fibroblast TNF
0.0




alpha + IL-1 beta


PBMC PHA-L
0.0
Lung fibroblast IL-4
3.8


Ramos (B cell) none A
0.0
Lung fibroblast IL-9
0.5


Ramos (B cell)
0.0
Lung fibroblast IL-13
5.7


ionomycin


B lymphocytes PWM
3.5
Lung fibroblast IFN
2.9




gamma


B lymphocytes CD40L
0.0
Dermal fibroblast
0.0


and IL-4

CCD1070 rest


EOL-1 dbcAMP
100.0
Dermal fibroblast
0.0




CCD1070 TNF alpha
0.0


EOL-1 dbcAMP
25.9
Dermal fibroblast


PMA/ionomycin

CCD1070 IL-1 beta


Dendritic cells none
3.8
Dermal fibroblast IFN
2.8




gamma


Dendritic cells LPS
2.6
Dermal fibroblast IL-4
4.8


Dendritic cells anti-
5.0
IBD Colitis 2
0.0


CD40


Monocytes rest
0.0
IBD Crohn's
0.0


Monocytes LPS
0.0
Colon
37.4


Macrophages rest
4.2
Lung
8.4


Macrophages LPS
0.0
Thymus
40.9


HUVEC none
0.0
Kidney
6.3


HUVEC starved
0.0










[2102] CNS_neurodegeneration_v1.0 Summary: Ag3273 Two experiments with the same probe and primer set produce results that are in excellent agreement. This panel confirms the expression of this gene at low to moderate levels in the brains of an independent group of individuals. Expression of this gene is found to be down-regulated in the temporal cortex of Alzheimer's disease patients. Therefore, up-regulation of this gene or its protein product, or treatment with specific agonists for this protein, may be of use in reversing the dementia/memory loss associated with Alzheimer's disease and neuronal death.


[2103] General_screening_panel_v1.4 Summary: Ag3273 Highest expression of the CG57460-01 gene is seen in fetal heart (CT=28.6). In addition, this gene is expressed at much higher levels in fetal heart when compared to expression in the adult heart (CT=38). Thus, expression of this gene may be used to differentiate between the fetal and adult source of this tissue. In addition, the higher expression in fetal heart suggests that this protein product may be involved in the development of this organ. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of heart disease.


[2104] This gene also shows highly specific brain expression. Please see Panel CNS_neurodegeneration for discussion of utility of this gene in the central nervous system.


[2105] In addition, expression of this gene appears to be upregulated in a number of cancer cell lines when compared to the normal tissues. Specifically, expression of this gene appears to be higher in ovarian, breast, lung and renal cancer cell lines when compared to their respective normal tissues. Therefore, therapeutic modulation of the activity of this gene or its protein may be of benefit in the treatment of ovarian, breast, lung and renal cancer. The CG57460-01 gene encodes a transmembrane protein with homology to N-acetyltransferase Camello 2, a protein involved in cellular adhesion (ref. 1).



REFERENCES

[2106] 1. Popsueva A E, Luchinskaya N N, Ludwig A V, Zinovjeva O Y, Poteryaev D A, Feigelman M M, Ponomarev M B, Berekelya L, Belyavsky A V. Overexpression of camello, a member of a novel protein family, reduces blastomere adhesion and inhibits gastrulation in Xenopus laevis. Dev Biol Jun. 15, 2001;234(2):483-96


[2107] Panel 4.1D Summary: Ag3273 Highest expression of the CG57460-01 is seen in eosinophils. In addition, differential expression is observed in the eosinophil cell line EOL-1 under resting conditions over that in EOL-1 cells stimulated by phorbol ester and ionomycin. Thus, this gene may be involved in eosinophil function. Therefore, therapeutic modulation of the expression or function of this gene may reduce eosinophil activation and be useful in the treatment of asthma and allergies.


[2108] In addition, significant expression in normal colon and thymus suggest a role for this gene in the normal homeostasis of these tissues. Therefore, therapeutic modulation of the expression or function of this gene may modulate immune function (T cell development) and be important for organ transplant, AIDS treatment or post chemotherapy immune reconstitution. Furthermore, since expression of this gene is decreased in colon samples from patients with IBD colitis and Crohn's disease relative to normal colon, therapeutic modulation of the activity of the protein encoded by this gene may be useful in the treatment of inflammatory bowel disease.


[2109] CS. CG57464-01


[2110] Expression of gene CG57464-01 was assessed using the primer-probe set Ag3248, described in Table CSA. Results of the RTQ-PCR runs are shown in Tables CSB, CSC, CSD and CSE.
1006TABLE CSAProbe Name Ag3248SEQStartIDPrimersSequencesLengthPositionNO:Forward5′-cctccctggtagaggtcaac-3′20929695ProbeTET-5′-ctactcagtgcccagcagccaggt-3′-24954696TAMRAReverse5′-tgtctgcatgcagcctatg-3′19996697


[2111]

1007





TABLE CSB










CNS_neurodegeneration_v1.0













Rel. Exp. (%)
Rel. Exp. (%)

Rel. Exp. (%)
Rel. Exp. (%)


Tissue
Ag3248, Run
Ag3248, Run
Tissue
Ag3248, Run
Ag3248, Run


Name
210037962
224063124
Name
210037962
224063124















AD 1 Hippo
26.4
4.8
Control
28.5
39.2





(Path) 3





Temporal





Ctx


AD 2 Hippo
73.2
71.7
Control
57.8
61.1





(Path) 4





Temporal





Ctx


AD 3 Hippo
21.6
5.6
AD 1
19.1
21.2





Occipital





Ctx


AD 4 Hippo
28.3
28.9
AD 2
0.0
0.0





Occipital





Ctx





(Missing)


AD 5 hippo
85.3
100.0
AD 3
13.0
15.9





Occipital





Ctx


AD 6 Hippo
70.2
72.7
AD 4
37.4
28.7





Occipital





Ctx


Control 2
64.6
49.3
AD 5
33.9
85.3


Hippo


Occipital





Ctx


Control 4
55.5
64.2
AD 6
58.6
14.4


Hippo


Occipital





Ctx


Control (Path)
46.3
0.9
Control 1
17.3
22.7


3 Hippo


Occipital





Ctx


AD 1 Temporal
28.9
24.1
Control 2
89.5
81.2


Ctx


Occipital





Ctx


AD 2 Temporal
57.4
62.4
Control 3
68.3
62.0


Ctx


Occipital





Ctx


AD 3 Temporal
18.9
16.7
Control 4
29.3
34.2


Ctx


Occipital





Ctx


AD 4 Temporal
42.3
29.9
Control
100.0
92.7


Ctx


(Path) 1





Occipital





Ctx


AD 5 Inf
77.4
97.3
Control
36.3
15.1


Temporal Ctx


(Path) 2





Occipital





Ctx


AD 5
69.7
87.7
Control
32.5
25.2


Sup Temporal


(Path) 3


Ctx


Occipital





Ctx


AD 6 Inf
39.2
87.1
Control
70.2
66.9


Temporal Ctx


(Path) 4





Occipital





Ctx


AD 6 Sup
73.2
70.7
Control 1
24.8
32.3


Temporal Ctx


Parietal Ctx


Control 1
25.3
26.1
Control 2
70.7
94.0


Temporal Ctx


Parietal Ctx


Control 2
43.5
77.4
Control 3
59.0
0.0


Temporal Ctx


Parietal Ctx


Control 3
74.2
49.3
Control
42.6
80.7


Temporal Ctx


(Path) 1





Parietal Ctx


Control 4
45.7
68.8
Control
67.4
59.9


Temporal Ctx


(Path) 2





Parietal Ctx


Control (Path)
63.3
58.6
Control
25.3
24.1


1 Temporal Ctx


(Path) 3





Parietal Ctx


Control (Path)
55.9
55.1
Control
78.5
79.0


2 Temporal Ctx


(Path) 4





Parietal Ctx










[2112]

1008





TABLE CSC










General_screening_panel_v1.4











Rel. Exp.

Rel. Exp.



(%) Ag3248,

(%) Ag3248,



Run

Run


Tissue Name
214693634
Tissue Name
214693634













Adipose
1.5
Renal ca. TK-10
3.6


Melanoma*
6.2
Bladder
7.6


Hs688(A).T


Melanoma*
5.8
Gastric ca. (liver met.)
16.8


Hs688(B).T

NCI-N87


Melanoma* M14
4.9
Gastric ca. KATO III
14.5


Melanoma*
5.3
Colon ca. SW-948
6.4


LOXIMVI


Melanoma* SK-
4.3
Colon ca. SW480
15.6


MEL-5


Squamous cell
3.3
Colon ca.* (SW480
9.1


carcinoma SCC-4

met) SW620


Testis Pool
1.5
Colon ca. HT29
7.1


Prostate ca.* (bone
2.3
Colon ca. HCT-116
7.5


met) PC-3


Prostate Pool
3.1
Colon ca. CaCo-2
8.7


Placenta
3.0
Colon cancer tissue
4.9


Uterus Pool
0.9
Colon ca. SW1116
10.2


Ovarian ca.
24.0
Colon ca. Colo-205
6.2


OVCAR-3


Ovarian ca. SK-
18.7
Colon ca. SW-48
7.5


OV-3


Ovarian ca.
4.1
Colon Pool
4.2


OVCAR-4


Ovarian ca.
33.0
Small Intestine Pool
4.5


OVCAR-5


Ovarian ca.
16.0
Stomach Pool
2.7


IGROV-1


Ovarian ca.
20.9
Bone Marrow Pool
1.3


OVCAR-8


Ovary
3.1
Fetal Heart
3.2


Breast ca. MCF-7
4.5
Heart Pool
2.6


Breast ca. MDA-
12.2
Lymph Node Pool
4.6


MB-231


Breast ca. BT 549
12.0
Fetal Skeletal Muscle
1.2


Breast ca. T47D
100.0
Skeletal Muscle Pool
4.0


Breast ca. MDA-N
9.7
Spleen Pool
4.1


Breast Pool
5.2
Thymus Pool
5.3


Trachea
3.1
CNS cancer
12.1




(glio/astro) U87-MG


Lung
0.4
CNS cancer
10.9




(glio/astro) U-118-MG


Fetal Lung
4.4
CNS cancer
16.0




(neuro; met) SK-N-AS


Lung ca. NCI-N417
3.1
CNS cancer (astro)
6.2




SF-539


Lung ca. LX-1
12.5
CNS cancer (astro)
15.3




SNB-75


Lung ca. NCI-H146
5.1
CNS cancer (glio)
13.2




SNB-19


Lung ca. SHP-77
1.5
CNS cancer (glio) SF-
25.9




295


Lung ca. A549
5.4
Brain (Amygdala)
4.7




Pool


Lung ca. NCI-H526
7.4
Brain (cerebellum)
8.5


Lung ca. NCI-H23
4.4
Brain (fetal)
2.1


Lung ca. NCI-H460
4.5
Brain (Hippocampus)
6.1




Pool


Lung ca. HOP-62
6.3
Cerebral Cortex Pool
6.0


Lung ca. NCI-H522
5.5
Brain (Substantia
8.1




nigra) Pool


Liver
3.2
Brain (Thalamus) Pool
7.8


Fetal Liver
2.3
Brain (whole)
3.4


Liver ca. HepG2
5.4
Spinal Cord Pool
6.6


Kidney Pool
4.5
Adrenal Gland
3.0


Fetal Kidney
3.1
Pituitary gland Pool
3.4


Renal ca. 786-0
7.4
Salivary Gland
4.3


Renal ca. A498
5.8
Thyroid (female)
6.1


Renal ca. ACHN
5.6
Pancreatic ca.
11.3




CAPAN2


Renal ca. UO-31
6.1
Pancreas Pool
5.2










[2113]

1009





TABLE CSD










Panel 2.2











Rel. Exp. (%)

Rel. Exp. (%)



Ag3248, Run

Ag3248,


Tissue Name
174441298
Tissue Name
Run 174441298













Normal Colon
14.4
Kidney Margin
100.0




(OD04348)


Colon cancer
6.3
Kidney malignant
6.3


(OD06064)

cancer (OD06204B)


Colon Margin
7.5
Kidney normal
9.3


(OD06064)

adjacent tissue




(OD06204E)


Colon cancer
8.0
Kidney Cancer
57.8


(OD06159)

(OD04450-01)


Colon Margin
5.3
Kidney Margin
16.2


(OD06159)

(OD04450-03)


Colon cancer
2.4
Kidney Cancer
10.8


(OD06297-04)

8120613


Colon Margin
6.3
Kidney Margin
16.7


(OD06297-05)

8120614


CC Gr.2 ascend colon
14.1
Kidney Cancer
9.0


(ODO3921)

9010320


CC Margin (ODO3921)
12.8
Kidney Margin
19.5




9010321


Colon cancer metastasis
4.4
Kidney Cancer
34.2


(OD06104)

8120607


Lung Margin
4.8
Kidney Margin
27.7


(OD06104)

8120608


Colon mets to lung
15.0
Normal Uterus
3.8


(OD04451-01)


Lung Margin
6.7
Uterine Cancer 064011
10.5


(OD04451-02)


Normal Prostate
9.0
Normal Thyroid
4.6


Prostate Cancer
7.5
Thyroid Cancer
18.6


(OD04410)

064010


Prostate Margin
11.6
Thyroid Cancer
24.0


(OD04410)

A302152


Normal Ovary
28.7
Thyroid Margin
13.3




A302153


Ovarian cancer
3.1
Normal Breast
4.0


(OD06283-03)


Ovarian Margin
1.1
Breast Cancer
9.3


(OD06283-07)

(OD04566)


Ovarian Cancer 064008
6.8
Breast Cancer 1024
6.9


Ovarian cancer
8.6
Breast Cancer
86.5


(OD06145)

(OD04590-01)


Ovarian Margin
17.8
Breast Cancer Mets
22.4


(OD06145)

(OD04590-03)


Ovarian cancer
2.0
Breast Cancer
47.3


(OD06455-03)

Metastasis (OD04655-




05)


Ovarian Margin
2.5
Breast Cancer 064006
9.8


(OD06455-07)


Normal Lung
4.7
Breast Cancer 9100266
5.8


Invasive poor diff. lung
9.0
Breast Margin
3.3


adeno (ODO4945-01)

9100265


Lung Margin
4.5
Breast Cancer
7.3


(ODO4945-03)

A209073


Lung Malignant Cancer
10.6
Breast Margin
17.0


(OD03126)

A2090734


Lung Margin
8.4
Breast cancer
8.6


(OD03126)

(OD06083)


Lung Cancer
8.7
Breast cancer node
8.2


(OD05014A)

metastasis (OD06083)


Lung Margin
8.6
Normal Liver
33.4


(OD05014B)


Lung cancer
6.3
Liver Cancer 1026
20.6


(OD06081)


Lung Margin
4.4
Liver Cancer 1025
29.1


(OD06081)


Lung Cancer
2.7
Liver Cancer 6004-T
27.4


(OD04237-01)


Lung Margin
16.7
Liver Tissue 6004-N
2.5


(OD04237-02)


Ocular Melanoma
25.0
Liver Cancer 6005-T
26.2


Metastasis


Ocular Melanoma
15.8
Liver Tissue 6005-N
58.2


Margin (Liver)


Melanoma Metastasis
3.8
Liver Cancer 064003
52.5


Melanoma Margin
2.6
Normal Bladder
10.7


(Lung)


Normal Kidney
12.4
Bladder Cancer 1023
6.8


Kidney Ca, Nuclear
32.3
Bladder Cancer
3.8


grade 2 (OD04338)

A302173


Kidney Margin
7.1
Normal Stomach
16.8


(OD04338)


Kidney Ca Nuclear
71.7
Gastric Cancer
9.2


grade 1/2 (OD04339)

9060397


Kidney Margin
14.6
Stomach Margin
10.4


(OD04339)

9060396


Kidney Ca, Clear cell
8.4
Gastric Cancer
1.7


type (OD04340)

9060395


Kidney Margin
31.2
Stomach Margin
7.5


(OD04340)

9060394


Kidney Ca, Nuclear
7.5
Gastric Cancer 064005
10.7


grade 3 (OD04348)










[2114]

1010





TABLE CSE










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3248, Run

Ag3248, Run


Tissue Name
164390952
Tissue Name
164390952













Secondary Th1 act
15.3
HUVEC IL-1beta
1.7


Secondary Th2 act
16.5
HUVEC IFN gamma
16.0


Secondary Tr1 act
15.5
HUVEC TNF alpha +
7.8




IFN gamma


Secondary Th1 rest
8.0
HUVEC TNF alpha +
9.2




IL4


Secondary Th2 rest
8.8
HUVEC IL-11
12.8


Secondary Tr1 rest
12.8
Lung Microvascular EC
19.1




none


Primary Th1 act
8.4
Lung Microvascular EC
13.8




TNF alpha + IL-1beta


Primary Th2 act
9.3
Microvascular Dermal
18.0




EC none


Primary Tr1 act
15.1
Microsvasular Dermal
6.9




EC TNF alpha + IL-1beta


Primary Th1 rest
12.3
Bronchial epithelium
21.3




TNF alpha + IL1beta


Primary Th2 rest
4.6
Small airway epithelium
13.5




none


Primary Tr1 rest
5.6
Small airway epithelium
45.4




TNF alpha + IL-1beta


CD45RA CD4
12.1
Coronery artery SMC rest
12.9


lymphocyte act


CD45RO CD4
12.0
Coronery artery SMC
15.2


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
12.5
Astrocytes rest
18.6


Secondary CD8
13.7
Astrocytes TNF alpha +
17.2


lymphocyte rest

IL-1beta


Secondary CD8
9.9
KU-812 (Basophil) rest
8.7


lymphocyte act


CD4 lymphocyte none
6.8
KU-812 (Basophil)
8.6




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
9.5
CCD1106
10.9


CD95 CH11

(Keratinocytes) none


LAK cells rest
15.2
CCD1106
12.2




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
13.6
Liver cirrhosis
7.4


LAK cells IL-2 + IL-12
9.1
Lupus kidney
10.7


LAK cells IL-2 + IFN
13.9
NCI-H292 none
42.6


gamma


LAK cells IL-2 + IL-18
9.7
NCI-H292 IL-4
48.3


LAK cells
1.5
NCI-H292 IL-9
54.3


PMA/ionomycin


NK Cells IL-2 rest
12.9
NCI-H292 IL-13
37.1


Two Way MLR 3 day
19.8
NCI-H292 IFN gamma
48.3


Two Way MLR 5 day
6.3
HPAEC none
17.9


Two Way MLR 7 day
9.7
HPAEC TNF alpha + IL-
5.0




1beta


PBMC rest
10.7
Lung fibroblast none
21.5


PBMC PWM
27.0
Lung fibroblast TNF
27.9




alpha + IL-1beta


PBMC PHA-L
12.0
Lung fibroblast IL-4
31.9


Ramos (B cell) none
27.9
Lung fibroblast IL-9
35.4


Ramos (B cell)
100.0
Lung fibroblast IL-13
18.6


ionomycin


B lymphocytes PWM
21.0
Lung fibroblast IFN
37.4




gamma


B lymphocytes CD40L
8.9
Dermal fibroblast
17.7


and IL-4

CCD1070 rest


EOL-1 dbcAMP
19.8
Dermal fibroblast
21.2




CCD1070 TNF alpha


EOL-1 dbcAMP
1.4
Dermal fibroblast
8.4


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
18.3
Dermal fibroblast IFN
16.8




gamma


Dendritic cells LPS
20.0
Dermal fibroblast IL-4
27.7


Dendritic cells anti-
22.1
IBD Colitis 2
3.0


CD40


Monocytes rest
12.6
IBD Crohn's
4.2


Monocytes LPS
2.6
Colon
28.5


Macrophages rest
20.6
Lung
12.0


Macrophages LPS
10.4
Thymus
53.6


HUVEC none
11.9
Kidney
20.0


HUVEC starved
15.6










[2115] CNS_neurodegeneration_v1.0 Summary: Ag3248 Results from two experiments using the same probe/primer set gave results that are in excellent agreement. This panel confirms the expression of this gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.


[2116] General_screening_panel_v1.4 Summary: Ag3248 Expression of the CG57464-01 gene is highest in a breast cancer cell line (CT=27). This also gene appears to be overexpressed in ovarian and CNS cancer cell lines when compared to the normal tissue controls. Thus, therapeutic modulation of the activity of this gene or its protein may be of benefit in the treatment of breast, ovarian and CNS cancer.


[2117] In addition, this gene is expressed at low levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[2118] Among tissues with metabolic or endocrine function, this gene is expressed at low levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.


[2119] Panel 2.2 Summary: Ag3248 This gene is expressed at low to moderate levels in the majority of samples on this panel, with highest expression detected in a sample derived from normal kidney (CT=28.6). Expression of the CG57464-01 gene appears to be upregulated in a number of breast cancer samples when compared to normal breast. Thus, therapeutic modulation of the activity of this gene or its protein product may be of benefit in the treatment of breast cancer.


[2120] Panel 4D Summary: Ag3248 Expression of the CG57464-01 gene is highest in Ramos B cells treated with ionomycin (CT=29). Therefore, expression of this gene may be used as a marker of activated B cells. In addition, this gene is expressed at relatively high levels in lung fibroblasts as well as in the mucoepidermoid cell line NCI-H292 independent of treatment (CTs=30), suggesting that therapeutic modulation of the activity of this gene or its protein product may be of benefit in the treatment of asthma and emphysema.


[2121] This gene is also expressed at low to moderate levels in a wide range of other cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues.


[2122] This pattern is in agreement with the expression profile in General_screening_panel_v1.5 and also suggests a role for the gene product in cell survival and proliferation.


[2123] Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.


[2124] CT. CG57466-01: Acetylglucosaminyltransferase


[2125] Expression of gene CG57466-01 was assessed using the primer-probe set Ag3249, described in Table CTA. Results of the RTQ-PCR runs are shown in Tables CTB, CTC and CTD.
1011TABLE CTAProbe Name Ag3249StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-accactaactgctcagccaata-3′22156698ProbeTET-5′-aacttgacccaccagccctggtt-3′-TAMRA23180699Reverse5′-tagaagagaaactgccggaact-3′22220700


[2126]

1012





TABLE CTB










CNS_neurodegeneration_v1.0











Rel.

Rel.



Exp. (%)

Exp. (%)



Ag3249,

Ag3249,



Run

Run


Tissue Name
210037963
Tissue Name
210037963













AD 1 Hippo
8.4
Control (Path) 3
5.6




Temporal Ctx


AD 2 Hippo
41.5
Control (Path) 4
27.2




Temporal Ctx


AD 3 Hippo
14.0
AD 1 Occipital Ctx
6.6


AD 4 Hippo
26.1
AD 2 Occipital Ctx
0.0




(Missing)


AD 5 Hippo
29.9
AD 3 Occipital Ctx
8.5


AD 6 Hippo
100.0
AD 4 Occipital Ctx
25.2


Control 2 Hippo
42.0
AD 5 Occipital Ctx
48.0


Control 4 Hippo
29.3
AD 6 Occipital Ctx
22.4


Control (Path) 3
5.6
Control 1 Occipital
6.1


Hippo

Ctx


AD 1 Temporal
10.7
Control 2 Occipital
51.4


Ctx

Ctx


AD 2 Temporal
25.5
Control 3 Occipital
22.1


Ctx

Ctx


AD 3 Temporal
9.9
Control 4 Occipital
15.8


Ctx

Ctx


AD 4 Temporal
29.9
Control (Path) 1
92.7


Ctx

Occipital Ctx


AD 5 Inf Temporal
25.5
Control (Path) 2
18.7


Ctx

Occipital Ctx


AD 5 Sup
27.4
Control (Path) 3
0.7


Temporal Ctx

Occipital Ctx


AD 6 Inf Temporal
87.1
Control (Path) 4
29.9


Ctx

Occipital Ctx


AD 6 Sup
5.0
Control 1 Parietal
13.7


Temporal Ctx

Ctx


Control 1
24.5
Control 2 Parietal
29.1


Temporal Ctx

Ctx


Control 2
41.2
Control 3 Parietal
25.7


Temporal Ctx

Ctx


Control 3
33.7
Control (Path) 1
64.2


Temporal Ctx

Parietal Ctx


Control 3
21.9
Control (Path) 2
25.9


Temporal Ctx

Parietal Ctx


Control (Path) 1
69.7
Control (Path) 3
1.9


Temporal Ctx

Parietal Ctx


Control (Path) 2
26.4
Control (Path) 4
39.8


Temporal Ctx

Parietal Ctx










[2127]

1013





TABLE CTC










General_screening_panel_v1.4











Rel.

Rel.



Exp. (%)

Exp. (%)



Ag3249,

Ag3249,



Run

Run


Tissue Name
214693635
Tissue Name
214693635













Adipose
5.6
Renal ca. TK-10
2.7


Melanoma*
0.4
Bladder
59.5


Hs688(A).T


Melanoma*
0.5
Gastric ca. (liver met.)
78.5


Hs688(B).T

NCI-N87


Melanoma* M14
8.8
Gastric ca. KATO III
60.3


Melanoma*
0.1
Colon ca. SW-948
0.5


LOXIMVI


Melanoma* SK-
15.2
Colon ca. SW480
4.4


MEL-5


Squamous cell
50.7
Colon ca.* (SW480
0.9


carcinoma SCC-4

met) SW620


Testis Pool
1.7
Colon ca. HT29
0.8


Prostate ca.* (bone
9.0
Colon ca. HCT-116
13.2


met) PC-3


Prostate Pool
1.8
Colon ca. CaCo-2
6.6


Placenta
10.9
Colon cancer tissue
26.6


Uterus Pool
0.9
Colon ca. SW1116
3.6


Ovarian ca.
3.8
Colon ca. Colo-205
0.1


OVCAR-3


Ovarian ca. SK-
6.1
Colon ca. SW-48
0.0


OV-3


Ovarian ca.
1.3
Colon Pool
6.2


OVCAR-4


Ovarian ca.
22.1
Small Intestine Pool
11.3


OVCAR-5


Ovarian ca.
7.5
Stomach Pool
6.7


IGROV-1


Ovarian ca.
1.4
Bone Marrow Pool
2.3


OVCAR-8


Ovary
24.5
Fetal Heart
11.6


Breast ca. MCF-7
0.7
Heart Pool
2.7


Breast ca. MDA-
1.4
Lymph Node Pool
7.1


MB-231


Breast ca. BT 549
1.8
Fetal Skeletal Muscle
0.4


Breast ca. T47D
37.9
Skeletal Muscle Pool
0.8


Breast ca. MDA-N
100.0
Spleen Pool
13.3


Breast Pool
4.0
Thymus Pool
3.7


Trachea
65.5
CNS cancer
0.0




(glio/astro) U87-MG


Lung
5.8
CNS cancer
0.7




(glio/astro) U-118-MG


Fetal Lung
87.7
CNS cancer
21.3




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.0
CNS cancer (astro)
0.1




SF-539


Lung ca. LX-1
29.5
CNS cancer (astro)
12.2




SNB-75


Lung ca. NCI-H146
0.6
CNS cancer (glio)
6.5




SNB-19


Lung ca. SHP-77
0.2
CNS cancer (glio) SF-
6.2




295


Lung ca. A549
12.9
Brain (Amygdala)
5.1




Pool


Lung ca. NCI-H526
0.0
Brain (cerebellum)
6.8


Lung ca. NCI-H23
2.3
Brain (fetal)
4.5


Lung ca. NCI-H460
0.2
Brain (Hippocampus)
6.7




Pool


Lung ca. HOP-62
5.0
Cerebral Cortex Pool
6.7


Lung ca. NCI-H522
0.4
Brain (Substantia
7.6




nigra) Pool


Liver
0.8
Brain (Thalamus) Pool
9.0


Fetal Liver
4.8
Brain (whole)
7.5


Liver ca. HepG2
0.0
Spinal Cord Pool
4.6


Kidney Pool
11.7
Adrenal Gland
40.6


Fetal Kidney
4.5
Pituitary gland Pool
10.5


Renal ca. 786-0
2.5
Salivary Gland
5.7


Renal ca. A498
1.4
Thyroid (female)
5.8


Renal ca. ACHN
22.2
Pancreatic ca.
43.8




CAPAN2


Renal ca. UO-31
32.8
Pancreas Pool
11.3










[2128]

1014





TABLE CTD










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3249, Run

Ag3249, Run


Tissue Name
164390953
Tissue Name
164390953













Secondary Th1 act
0.2
HUVEC IL-1beta
0.4


Secondary Th2 act
0.0
HUVEC IFN gamma
1.0


Secondary Tr1 act
0.0
HUVEC TNF alpha +
0.5




IFN gamma


Secondary Th1 rest
0.0
HUVEC TNF alpha +
0.6




IL4


Secondary Th2 rest
0.1
HUVEC IL-11
0.9


Secondary Tr1 rest
0.0
Lung Microvascular EC
1.4




none


Primary Th1 act
0.2
Lung Microvascular EC
4.5




TNF alpha + IL-1beta


Primary Th2 act
0.0
Microvascular Dermal
0.9




EC none


Primary Tr1 act
0.0
Microsvasular Dermal
7.7




EC TNF alpha + IL-1beta


Primary Th1 rest
0.1
Bronchial epithelium
3.6




TNF alpha + IL1beta


Primary Th2 rest
0.0
Small airway epithelium
0.2




none


Primary Tr1 rest
0.1
Small airway epithelium
5.8




TNF alpha + IL-1beta


CD45RA CD4
0.5
Coronery artery SMC rest
0.0


lymphocyte act


CD45RO CD4
0.1
Coronery artery SMC
0.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
0.6
Astrocytes rest
0.8


Secondary CD8
0.0
Astrocytes TNF alpha +
3.1


lymphocyte rest

IL-1beta


Secondary CD8
0.1
KU-812 (Basophil) rest
2.7


lymphocyte act


CD4 lymphocyte none
1.1
KU-812 (Basophil)
3.8




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
0.1
CCD1106
1.6


CD95 CH11

(Keratinocytes) none


LAK cells rest
1.9
CCD1106
1.3




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
5.0
Liver cirrhosis
3.2


LAK cells IL-2 + IL-12
1.6
Lupus kidney
1.3


LAK cells IL-2 + IFN
5.0
NCI-H292 none
100.0


gamma


LAK cells IL-2 + IL-18
4.3
NCI-H292 IL-4
87.7


LAK cells
6.1
NCI-H292 IL-9
96.6


PMA/ionomycin


NK Cells IL-2 rest
12.7
NCI-H292 IL-13
54.0


Two Way MLR 3 day
0.6
NCI-H292 IFN gamma
25.2


Two Way MLR 5 day
1.6
HPAEC none
0.4


Two Way MLR 7 day
0.9
HPAEC TNF alpha + IL-
6.3




1beta


PBMC rest
9.4
Lung fibroblast none
0.1


PBMC PWM
3.7
Lung fibroblast TNF
0.3




alpha + IL-1beta


PBMC PHA-L
0.7
Lung fibroblast IL-4
0.7


Ramos (B cell) none
0.1
Lung fibroblast IL-9
0.0


Ramos (B cell)
2.0
Lung fibroblast IL-13
0.3


ionomycin


B lymphocytes PWM
2.7
Lung fibroblast IFN
0.4




gamma


B lymphocytes CD40L
5.8
Dermal fibroblast
0.1


and IL-4

CCD1070 rest


EOL-1 dbcAMP
26.6
Dermal fibroblast
0.8




CCD1070 TNF alpha


EOL-1 dbcAMP
8.4
Dermal fibroblast
0.0


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
3.2
Dermal fibroblast IFN
0.0




gamma


Dendritic cells LPS
2.5
Dermal fibroblast IL-4
0.0


Dendritic cells anti-
1.3
IBD Colitis 2
1.4


CD40


Monocytes rest
0.4
IBD Crohn's
4.2


Monocytes LPS
10.5
Colon
48.6


Macrophages rest
1.1
Lung
19.5


Macrophages LPS
17.9
Thymus
2.5


HUVEC none
0.8
Kidney
3.9


HUVEC starved
1.1










[2129] CNS_neurodegeneration_v1.0 Summary: Ag3249 This panel confirms the expression of this gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.


[2130] General_screening_panel_v1.4 Summary: Ag3249 The CG57466-01 gene encodes a protein with homology to beta-1,3-galactosyltransferases, which catalyze the formation of type I oligosaccharides (ref. 1). Expression of this gene is highest in a breast cancer cell line (CT=28.1). In addition, expression of this gene appears to be upregulated in pancreatic and gastric cancer cell lines when compared to their respective normal tissues. Thus, therapeutic modulation of the activity of this gene or its protein product may be of benefit in the treatment of breast, pancreatic and gastric cancer.


[2131] This gene also shows significant levels of expression in trachea, bladder and fetal lung. Interestingly, CG57466-01 gene expression is much higher in fetal lung (CT=28.3) than in adult lung (CT=32.2), suggesting that expression of this gene can be used to distinguish adult from fetal lung.


[2132] In addition, this gene is expressed at low levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[2133] Among tissues with metabolic or endocrine function, this gene is expressed at low to moderate levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, heart, fetal liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.



REFERENCES

[2134] 1. Shiraishi N, Natsume A, Togayachi A, Endo T, Akashima T, Yamada Y, Imai N, Nakagawa S, Koizumi S, Sekine S, Narimatsu H, Sasaki K. Identification and characterization of three novel beta 1,3-N-acetylglucosaminyltransferases structurally related to the beta 1,3-galactosyltransferase family. J Biol Chem Feb. 2, 2001;276(5):3498


[2135] Panel 4D Summary: Ag3249 This transcript is most highly expressed in a cluster of treated and untreated samples derived from the NCI-H292 cell line, a human airway epithelial cell line that produces mucins (CTs=30-32). Mucus overproduction is an important feature of bronchial asthma and chronic obstructive pulmonary disease samples. The transcript is also expressed at lower but still significant levels in small airway epithelium treated with IL-1 beta and TNF-alpha. The expression of the transcript in this mucoepidermoid cell line that is often used as a model for airway epithelium (NCI-H292 cells) suggests that this transcript may be important in the proliferation or activation of airway epithelium. Therefore, therapeutics designed with the protein encoded by the transcript may reduce or eliminate symptoms caused by inflammation in lung epithelia in chronic obstructive pulmonary disease, asthma, allergy, and emphysema.


[2136] CU. CG57468-01: Multidrug Resistance Protein 1


[2137] Expression of gene CG57468-01 was assessed using the primer-probe set Ag3250, described in Table CUA. Results of the RTQ-PCR runs are shown in Tables CUB.
1015TABLE CUAProbe Name Ag3250StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-agcaggggaaattttaacgat-3′212391701ProbeTET-5′-agacacttggccttcaaagccatgtt-3′-TAMRA262419702Reverse5′-caaaccaggcaatatcctgata-3′222446703


[2138]

1016





TABLE CUB










General_screening_panel_v1.4











Rel.

Rel.



Exp. (%)

Exp. (%)



Ag3250,

Ag3250,



Run

Run


Tissue Name
214693636
Tissue Name
214693636













Adipose
0.1
Renal ca. TK-10
0.0


Melanoma*
0.0
Bladder
0.0


Hs688(A).T


Melanoma*
0.0
Gastric ca. (liver met.)
0.0


Hs688(B).T

NCI-N87


Melanoma* M14
0.0
Gastric ca. KATO III
0.0


Melanoma*
0.0
Colon ca. SW-948
11.9


LOXIMVI


Melanoma* SK-
0.6
Colon ca. SW480
0.0


MEL-5


Squamous cell
0.0
Colon ca.* (SW480
0.0


carcinoma SCC-4

met) SW620


Testis Pool
0.0
Colon ca. HT29
0.0


Prostate ca.* (bone
0.0
Colon ca. HCT-116
0.0


met) PC-3


Prostate Pool
0.0
Colon ca. CaCo-2
0.0


Placenta
0.0
Colon cancer tissue
0.0


Uterus Pool
0.0
Colon ca. SW1116
0.0


Ovarian ca.
0.0
Colon ca. Colo-205
0.0


OVCAR-3


Ovarian ca. SK-
0.0
Colon ca. SW-48
0.0


OV-3


Ovarian ca.
0.0
Colon Pool
0.1


OVCAR-4


Ovarian ca.
0.0
Small Intestine Pool
0.0


OVCAR-5


Ovarian ca.
0.0
Stomach Pool
0.0


IGROV-1


Ovarian ca.
0.0
Bone Marrow Pool
0.0


OVCAR-8


Ovary
0.0
Fetal Heart
0.0


Breast ca. MCF-7
0.0
Heart Pool
0.7


Breast ca. MDA-
0.0
Lymph Node Pool
0.8


MB-231


Breast ca. BT 549
0.0
Fetal Skeletal Muscle
0.0


Breast ca. T47D
0.0
Skeletal Muscle Pool
0.0


Breast ca. MDA-N
0.3
Spleen Pool
0.0


Breast Pool
100.0
Thymus Pool
0.0


Trachea
0.0
CNS cancer
0.0




(glio/astro) U87-MG


Lung
0.0
CNS cancer
0.0




(glio/astro) U-118-MG


Fetal Lung
0.1
CNS cancer
0.0




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.0
CNS cancer (astro)
0.0




SF-539


Lung ca. LX-1
0.0
CNS cancer (astro)
0.0




SNB-75


Lung ca. NCI-H146
0.0
CNS cancer (glio)
0.0




SNB-19


Lung ca. SHP-77
0.0
CNS cancer (glio) SF-
0.0




295


Lung ca. A549
0.0
Brain (Amygdala)
0.0




Pool


Lung ca. NCI-H526
0.0
Brain (cerebellum)
0.0


Lung ca. NCI-H23
0.0
Brain (fetal)
0.0


Lung ca. NCI-H460
0.0
Brain (Hippocampus)
0.0




Pool


Lung ca. HOP-62
0.0
Cerebral Cortex Pool
0.0


Lung ca. NCI-H522
0.0
Brain (Substantia
0.0




nigra) Pool


Liver
9.5
Brain (Thalamus) Pool
0.0


Fetal Liver
21.0
Brain (whole)
0.0


Liver ca. HepG2
0.0
Spinal Cord Pool
0.0


Kidney Pool
17.4
Adrenal Gland
0.0


Fetal Kidney
6.5
Pituitary gland Pool
0.0


Renal ca. 786-0
0.0
Salivary Gland
0.0


Renal ca. A498
0.0
Thyroid (female)
0.0


Renal ca. ACHN
0.0
Pancreatic ca.
0.0




CAPAN2


Renal ca. UO-31
0.0
Pancreas Pool
0.0










[2139] CNS_neurodegeneration v1.0 Summary: Ag3250 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[2140] General_screening_panel_v1.4 Summary: Ag3250 Expression of the CG57468-01 gene is highest in normal breast (CT=23.8). In addition, this gene is highly expressed in fetal/adult kidney and fetal/adult liver (CTs=26-27). Thus, expression of this gene may be used to distinguish these tissues from the other samples on this panel. Strikingly, expression of this gene is much lower in breast, kidney, and liver cancer cell lines. Therapeutic modulation of the activity of this gene or its protein product may be of benefit in the treatment of these types of cancers.


[2141] Panel 4D Summary: Ag3250 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[2142] CV. CG59609-01: Peptidyl-Prolyl Cis-Trans Isomerase A


[2143] Expression of gene CG59609-01 was assessed using the primer-probe set Ag3494, described in Table CVA. Results of the RTQ-PCR runs are shown in Tables CVB and CVC.
1017TABLE CVAphc,1 Probe Name Ag3494StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-ccgttctatcagccatggt-3′193704ProbeTET-5′-ccccaccaggttcttagacatcatcg-3′-TAMRA2625705Reverse5′-aaggagacacgtcccaagag-3′2062706


[2144]

1018





TABLE CVB










General_screening_panel_v1.4











Rel.

Rel.



Exp. (%)

Exp. (%)



Ag3494,

Ag3494,



Run

Run


Tissue Name
217215292
Tissue Name
217215292













Adipose
0.0
Renal ca.TK-10
0.0


Melanoma*
0.0
Bladder
0.0


Hs688(A).T


Melanoma*
0.0
Gastric ca. (liver met.)
0.0


Hs688(B).T

NCI-N87


Melanoma* M14
25.5
Gastric ca. KATO III
0.0


Melanoma*
0.0
Colon ca. SW-948
0.0


LOXIMVI


Melanoma* SK-
0.0
Colon ca. SW480
0.0


MEL-5


Squamous cell
33.4
Colon ca.* (SW480
0.0


carcinoma SCC-4

met) SW620


Testis Pool
100.0
Colon ca. HT29
0.0


Prostate ca.* (bone
0.0
Colon ca. HCT-116
0.0


met) PC-3


Prostate Pool
0.0
Colon ca. CaCo-2
0.0


Placenta
0.0
Colon cancer tissue
0.0


Uterus Pool
0.0
Colon ca. SW1116
0.0


Ovarian ca.
0.0
Colon ca. Colo-205
0.0


OVCAR-3


Ovarian ca. SK-
0.0
Colon ca. SW-48
0.0


OV-3


Ovarian ca.
0.0
Colon Pool
0.0


OVCAR-4


Ovarian ca.
0.0
Small Intestine Pool
0.0


OVCAR-5


Ovarian ca.
79.0
Stomach Pool
0.0


IGROV-1


Ovarian ca.
0.0
Bone Marrow Pool
0.0


OVCAR-8


Ovary
0.0
Fetal Heart
0.0


Breast ca. MCF-7
0.0
Heart Pool
0.0


Breast ca. MDA-
41.8
Lymph Node Pool
0.0


MB-231


Breast ca. BT 549
0.0
Fetal Skeletal Muscle
0.0


Breast ca. T47D
0.0
Skeletal Muscle Pool
0.0


Breast ca. MDA-N
86.5
Spleen Pool
0.0


Breast Pool
0.0
Thymus Pool
0.0


Trachea
0.0
CNS cancer
0.0




(glio/astro) U87-MG


Lung
0.0
CNS cancer
0.0




(glio/astro) U-118-MG


Fetal Lung
0.0
CNS cancer
0.0




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.0
CNS cancer (astro)
0.0




SF-539


Lung ca. LX-1
0.0
CNS cancer (astro)
0.0




SNB-75


Lung ca. NCI-H146
0.0
CNS cancer (glio)
0.0




SNB-19


Lung ca. SHP-77
40.6
CNS cancer (glio) SF-
0.0




295


Lung ca. A549
0.0
Brain (Amygdala)
0.0




Pool


Lung ca. NCI-H526
0.0
Brain (cerebellum)
0.0


Lung ca. NCI-H23
0.0
Brain (fetal)
0.0


Lung ca. NCI-H460
0.0
Brain (Hippocampus)
0.0




Pool


Lung ca. HOP-62
0.0
Cerebral Cortex Pool
0.0


Lung ca. NCI-H522
0.0
Brain (Substantia
0.0




nigra) Pool


Liver
0.0
Brain (Thalamus) Pool
0.0


Fetal Liver
0.0
Brain (whole)
0.0


Liver ca. HepG2
0.0
Spinal Cord Pool
0.0


Kidney Pool
47.0
Adrenal Gland
0.0


Fetal Kidney
0.0
Pituitary gland Pool
0.0


Renal ca. 786-0
0.0
Salivary Gland
0.0


Renal ca. A498
0.0
Thyroid (female)
0.0


Renal ca. ACHN
0.0
Pancreatic ca.
0.0




CAPAN2


Renal ca. UO-31
0.0
Pancreas Pool
0.0










[2145]

1019





TABLE CVC










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3494, Run

Ag3494, Run


Tissue Name
166441744
Tissue Name
166441744













Secondary Th1 act
0.0
HUVEC IL-1beta
0.0


Secondary Th2 act
0.0
HUVEC IFN gamma
0.0


Secondary Tr1 act
0.0
HUVEC TNF alpha +
0.0




IFN gamma


Secondary Th1 rest
0.0
HUVEC TNF alpha +
0.0




IL4


Secondary Th2 rest
0.0
HUVEC IL-11
0.0


Secondary Tr1 rest
0.0
Lung Microvascular EC
0.0




none


Primary Th1 act
0.0
Lung Microvascular EC
0.0




TNF alpha + IL-1beta


Primary Th2 act
0.0
Microvascular Dermal
0.0




EC none


Primary Tr1 act
0.0
Microsvasular Dermal
0.0




EC TNF alpha + IL-1beta


Primary Th1 rest
0.0
Bronchial epithelium
0.0




TNF alpha + IL1beta


Primary Th2 rest
0.0
Small airway epithelium
0.0




none


Primary Tr1 rest
0.0
Small airway epithelium
0.0




TNF alpha + IL-1beta


CD45RA CD4
0.0
Coronery artery SMC rest
0.0


lymphocyte act


CD45RO CD4
0.0
Coronery artery SMC
0.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
0.0
Astrocytes rest
0.0


Secondary CD8
0.0
Astrocytes TNF alpha +
0.0


lymphocyte rest

IL-1beta


Secondary CD8
0.0
KU-812 (Basophil) rest
0.0


lymphocyte act


CD4 lymphocyte none
0.0
KU-812 (Basophil)
0.0




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
0.0
CCD1106
0.0


CD95 CH11

(Keratinocytes) none


LAK cells rest
0.0
CCD1106
0.0




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
0.0
Liver cirrhosis
100.0


LAK cells IL-2 + IL-12
5.6
Lupus Kidney
4.6


LAK cells IL-2 + IFN
0.0
NCI-H292 none
0.0


gamma


LAK cells IL-2 + IL-18
0.0
NCI-H292 IL-4
0.0


LAK cells
0.0
NCI-H292 IL-9
0.0


PMA/ionomycin


NK Cells IL-2 rest
0.0
NCI-H292 IL-13
0.0


Two Way MLR 3 day
0.0
NCI-H292 IFN gamma
0.0


Two Way MLR 5 day
0.0
HPAEC none
0.0


Two Way MLR 7 day
0.0
HPAEC TNF alpha + IL-
0.0




1beta


PBMC rest
0.0
Lung fibroblast none
0.0


PBMC PWM
0.0
Lung fibroblast TNF
0.0




alpha + IL-1beta


PBMC PHA-L
0.0
Lung fibroblast IL-4
0.0


Ramos (B cell) none
0.0
Lung fibroblast IL-9
0.0


Ramos (B cell)
0.0
Lung fibroblast IL-13
0.0


ionomycin


B lymphocytes PWM
0.0
Lung fibroblast IFN
0.0




gamma


B lymphocytes CD40L
0.0
Dermal fibroblast
7.7


and IL-4

CCD1070 rest


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0




CCD1070 TNF alpha


EOL-1 dbcAMP
0.0
Dermal fibroblast
1.4


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
0.0
Dermal fibroblast IFN
0.0




gamma


Dendritic cells LPS
0.0
Dermal fibroblast IL-4
0.0


Dendritic cells anti-
0.0
IBD Colitis 2
26.2


CD40


Monocytes rest
0.0
IBD Crohn's
13.8


Monocytes LPS
0.0
Colon
17.6


Macrophages rest
0.0
Lung
8.1


Macrophages LPS
0.0
Thymus
16.5


HUVEC none
0.0
Kidney
0.0


HUVEC starved
0.0










[2146] CNS_neurodegeneration_v1.0 Summary: Ag3494 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[2147] General_screening_panel_v1.4 Summary: Ag3494 Expression of the CG59609-01 gene is highest in testis (CT=34.3). In addition, low but significant expression of this gene is detected in a breast cancer cell line and an ovarian cancer cell line. Thus, expression of this gene may be used to distinguish these samples from the other samples on this panel. Furthermore, therapeutic modulation of the activity of this gene may be of benefit in the treatment of fertility, breast cancer, and ovarian cancer.


[2148] Panel 4D Summary: Ag3494 Expression of the CG59609-01 gene is highest in a liver cirrhosis sample (CT=34.3). In addition, low but significant expression of this gene is detected in samples from thymus as well as from normal and IBD colon. Thus, expression of this gene may be used to distinguish these samples from the other samples on this panel. Furthermore, therapies designed with the protein encoded for by this gene may potentially modulate liver function and play a role in the identification and treatment of inflammatory or autoimmune diseases which effect the liver including liver cirrhosis and fibrosis.


[2149] CW. CG59613-01: Proliferating Cell Nuclear Antigen


[2150] Expression of gene CG59613-01 was assessed using the primer-probe set Ag3496, described in Table CWA. Results of the RTQ-PCR runs are shown in Tables CWB and
1020TABLE CWAProbe Name Ag3496StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-cacataccactgtgaccacaac-3′22238707ProbeTET-5′-cctcaccagcatgtccaaaatgctaa-3′-TAMRA26277708Reverse5′-tgtcttcactgccattgttgta-3′22305709


[2151]

1021





TABLE CWB










General_screening_panel_v1.4











Rel.

Rel.



Exp. (%)

Exp. (%)



Ag3496,

Ag3496,



Run

Run


Tissue Name
217217871
Tissue Name
217217871













Adipose
9.6
Renal ca. TK-10
21.8


Melanoma*
25.2
Bladder
11.4


Hs688(A).T


Melanoma*
20.4
Gastric ca. (liver met.)
3.9


Hs688(B).T

NCI-N87


Melanoma* M14
0.0
Gastric ca. KATO III
1.1


Melanoma*
0.0
Colon ca. SW-948
0.0


LOXIMVI


Melanoma* SK-
1.5
Colon ca. SW480
1.7


MEL-5


Squamous cell
5.4
Colon ca.* (SW480
2.0


carcinoma SCC-4

met) SW620


Testis Pool
56.3
Colon ca. HT29
3.9


Prostate ca.* (bone
2.6
Colon ca. HCT-116
12.9


met) PC-3


Prostate Pool
37.6
Colon ca. CaCo-2
8.4


Placenta
0.0
Colon cancer tissue
1.4


Uterus Pool
21.5
Colon ca. SW1116
0.0


Ovarian ca.
18.3
Colon ca. Colo-205
0.0


OVCAR-3


Ovarian ca. SK-
1.9
Colon ca. SW-48
0.0


OV-3


Ovarian ca.
8.0
Colon Pool
29.9


OVCAR-4


Ovarian ca.
2.9
Small Intestine Pool
57.8


OVCAR-5


Ovarian ca.
0.0
Stomach Pool
38.7


IGROV-1


Ovarian ca.
0.0
Bone Marrow Pool
6.3


OVCAR-8


Ovary
4.9
Fetal Heart
6.2


Breast ca. MCF-7
4.3
Heart Pool
12.3


Breast ca. MDA-
6.4
Lymph Node Pool
64.6


MB-231


Breast ca. BT 549
4.7
Fetal Skeletal Muscle
31.6


Breast ca. T47D
12.9
Skeletal Muscle Pool
0.0


Breast ca. MDA-N
0.0
Spleen Pool
1.7


Breast Pool
47.6
Thymus Pool
47.3


Trachea
26.1
CNS cancer
2.3




(glio/astro) U87-MG


Lung
7.7
CNS cancer
22.5




(glio/astro) U-118-MG


Fetal Lung
82.9
CNS cancer
0.9




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.0
CNS cancer (astro)
1.8




SF-539


Lung ca. LX-1
0.0
CNS cancer (astro)
35.4




SNB-75


Lung ca. NCI-H146
0.0
CNS cancer (glio)
0.0




SNB-19


Lung ca. SHP-77
3.7
CNS cancer (glio) SF-
9.2




295


Lung ca. A549
0.0
Brain (Amygdala)
0.0




Pool


Lung ca. NCI-H526
0.0
Brain (cerebellum)
0.0


Lung ca. NCI-H23
46.0
Brain (fetal)
23.8


Lung ca. NCI-H460
0.5
Brain (Hippocampus)
0.0




Pool


Lung ca. HOP-62
7.5
Cerebral Cortex Pool
1.6


Lung ca. NCI-H522
2.1
Brain (Substantia
3.8




nigra) Pool


Liver
0.0
Brain (Thalamus) Pool
3.2


Fetal Liver
7.9
Brain (whole)
4.2


Liver ca. HepG2
0.0
Spinal Cord Pool
1.9


Kidney Pool
80.7
Adrenal Gland
1.7


Fetal Kidney
100.0
Pituitary gland Pool
0.7


Renal ca. 786-0
13.3
Salivary Gland
6.2


Renal ca. A498
0.0
Thyroid (female)
2.6


Renal ca. ACHN
23.8
Pancreatic ca.
5.5




CAPAN2


Renal ca. UO-31
13.7
Pancreas Pool
48.6










[2152]

1022





TABLE CWC










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3496, Run

Ag3496, Run


Tissue Name
166441888
Tissue Name
166441888













Secondary Th1 act
0.0
HUVEC IL-1beta
0.7


Secondary Th2 act
0.7
HUVEC IFN gamma
1.0


Secondary Tr1 act
0.0
HUVEC TNF alpha +
0.0




IFN gamma


Secondary Th1 rest
0.7
HUVEC TNF alpha +
0.6




IL4


Secondary Th2 rest
1.2
HUVEC IL-11
0.4


Secondary Tr1 rest
0.4
Lung Microvascular EC
1.0




none


Primary Th1 act
0.3
Lung Microvascular EC
1.0




TNF alpha + IL-1beta


Primary Th2 act
1.2
Microvascular Dermal
0.4




EC none


Primary Tr1 act
0.8
Microsvasular Dermal
0.2




EC TNF alpha + IL-1beta


Primary Th1 rest
1.5
Bronchial epithelium
5.2




TNF alpha + IL1beta


Primary Th2 rest
1.0
Small airway epithelium
6.6




none


Primary Tr1 rest
1.5
Small airway epithelium
100.0




TNF alpha + IL-1beta


CD45RA CD4
2.1
Coronery artery SMC rest
2.6


lymphocyte act


CD45RO CD4
0.9
Coronery artery SMC
1.5


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
2.1
Astrocytes rest
13.1


Secondary CD8
0.0
Astrocytes TNF alpha +
7.4


lymphocyte rest

IL-1beta


Secondary CD8
0.0
KU-812 (Basophil) rest
4.2


lymphocyte act


CD4 lymphocyte none
1.8
KU-812 (Basophil)
5.2




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
0.7
CCD1106
17.9


CD95 CH11

(Keratinocytes) none


LAK cells rest
0.0
CCD1106
82.4




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
2.3
Liver cirrhosis
17.2


LAK cells IL-2 + IL-12
1.7
Lupus Kidney
9.3


LAK cells IL-2 + IFN
2.3
NCI-H292 none
0.3


gamma


LAK cells IL-2 + IL-18
3.1
NCI-H292 IL-4
0.8


LAK cells
0.2
NCI-H292 IL-9
3.0


PMA/ionomycin


NK Cells IL-2 rest
2.7
NCI-H292 IL-13
1.9


Two Way MLR 3 day
3.3
NCI-H292 IFN gamma
0.5


Two Way MLR 5 day
0.0
HPAEC none
0.3


Two Way MLR 7 day
0.2
HPAEC TNF alpha + IL-
0.6




1beta


PBMC rest
1.0
Lung fibroblast none
12.3


PBMC PWM
1.7
Lung fibroblast TNF
2.9




alpha + IL-1beta


PBMC PHA-L
0.7
Lung fibroblast IL-4
11.0


Ramos (B cell) none
0.0
Lung fibroblast IL-9
5.3


Ramos (B cell)
0.0
Lung fibroblast IL-13
10.4


ionomycin


B lymphocytes PWM
0.9
Lung fibroblast IFN
11.9




gamma


B lymphocytes CD40L
2.8
Dermal fibroblast
11.7


and IL-4

CCD1070 rest


EOL-1 dbcAMP
0.0
Dermal fibroblast
5.8




CCD1070 TNF alpha


EOL-1 dbcAMP
0.9
Dermal fibroblast
2.3


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
0.1
Dermal fibroblast IFN
8.8




gamma


Dendritic cells LPS
0.7
Dermal fibroblast IL-4
11.3


Dendritic cells anti-
0.6
IBD Colitis 2
2.6


CD40


Monocytes rest
0.7
IBD Crohn's
1.3


Monocytes LPS
0.0
Colon
11.4


Macrophages rest
0.0
Lung
1.9


Macrophages LPS
0.0
Thymus
3.8


HUVEC none
1.0
Kidney
7.2


HUVEC starved
1.4










[2153] CNS_neurodegeneration_v1.0 Summary: Ag3496 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[2154] General_screening_panel_v1.4 Summary: Ag3496 Expression of the CG59613-01 gene is highest in fetal and adult kidney (CTs=31). This gene is also expressed at higher levels in fetal lung (CT=31.4) than in adult lung (CT=34.8), suggesting that expression of this gene can be used to distinguish adult and fetal lung and that this gene may play a role in lung development and regeneration. Differentially higher expression in fetal tissues also occurs in brain and skeletal muscle.


[2155] In general, expression of this gene is associated with normal tissues rather than cancer cell lines. Specifically, CG59613-01 gene expression is downregulated in pancreatic, colon, gastric, renal, lung, breast and prostate cancer cell lines when compared to their respective normal tissues. Therefore, therapeutic modulation of the activity of this gene may be of benefit in the treatment of these cancers.


[2156] Among tissues with metabolic or endocrine function, this gene is expressed at low levels in pancreas, adipose, adrenal gland, fetal skeletal muscle, and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.


[2157] Panel 4D Summary: Ag3496 Expression of the CG59613-01 gene is highest in small airway epithelium treated with TNF alpha and IL-1 beta (CT=29.4). In addition, this gene is substantially upregulated in keratinocytes treated with TNF alpha and IL-1 beta. Low expression of this gene is also seen in lung and dermal fibroblasts independent of treatment. Therefore, therapeutics designed with the protein encoded by the transcript may reduce or eliminate symptoms caused by inflammation of the lung and skin in chronic obstructive pulmonary disease, asthma, allergy, emphysema, and psoriasis.


[2158] CX. CG59619-01: Actin, Cytoplasmic 2


[2159] Expression of gene CG59619-01 was assessed using the primer-probe set Ag3498, described in Table CXA. Results of the RTQ-PCR runs are shown in Tables CXB and CXC.
1023TABLE CXAProbe Name Ag3498StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-tgatatggacatccccaaag-3′20860710ProbeTET-5′-acctgtacgccaacacagtgctgtct-3′-TAMRA26880711Reverse5′-atctccttctgcatcctattgg-3′22934712


[2160]

1024





TABLE CXB










General_screening_panel_v1.4











Rel.

Rel.



Exp. (%)

Exp. (%)



Ag3498,

Ag3498,



Run

Run


Tissue Name
217217873
Tissue Name
217217873













Adipose
4.7
Renal ca. TK-10
0.0


Melanoma*
0.0
Bladder
3.3


Hs688(A).T


Melanoma*
0.0
Gastric ca. (liver met.)
0.0


Hs688(B).T

NCI-N87


Melanoma* M14
0.0
Gastric ca. KATO III
0.0


Melanoma*
0.0
Colon ca. SW-948
0.0


LOXIMVI


Melanoma* SK-
0.0
Colon ca. SW480
0.0


MEL-5


Squamous cell
0.0
Colon ca.* (SW480
0.0


carcinoma SCC-4

met) SW620


Testis Pool
55.1
Colon ca. HT29
0.0


Prostate ca.* (bone
0.0
Colon ca. HCT-116
8.7


met) PC-3


Prostate Pool
0.0
Colon ca. CaCo-2
4.9


Placenta
0.0
Colon cancer tissue
0.0


Uterus Pool
0.0
Colon ca. SW1116
0.0


Ovarian ca.
6.6
Colon ca. Colo-205
0.0


OVCAR-3


Ovarian ca. SK-
9.5
Colon ca. SW-48
0.0


OV-3


Ovarian ca.
0.0
Colon Pool
18.3


OVCAR-4


Ovarian ca.
17.9
Small Intestine Pool
26.2


OVCAR-5


Ovarian ca.
0.0
Stomach Pool
7.2


IGROV-1


Ovarian ca.
0.0
Bone Marrow Pool
0.0


OVCAR-8


Ovary
2.9
Fetal Heart
6.4


Breast ca. MCF-7
0.0
Heart Pool
11.2


Breast ca. MDA-
0.0
Lymph Node Pool
34.2


MB-231


Breast ca. BT 549
8.4
Fetal Skeletal Muscle
12.9


Breast ca. T47D
2.5
Skeletal Muscle Pool
10.8


Breast ca. MDA-N
0.0
Spleen Pool
4.7


Breast Pool
13.7
Thymus Pool
27.0


Trachea
5.4
CNS cancer
0.0




(glio/astro) U87-MG


Lung
7.0
CNS cancer
2.2




(glio/astro) U-118-MG


Fetal Lung
7.9
CNS cancer
0.0




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.0
CNS cancer (astro)
0.0




SF-539


Lung ca. LX-1
0.0
CNS cancer (astro)
0.0




SNB-75


Lung ca. NCI-H146
3.1
CNS cancer (glio)
0.0




SNB-19


Lung ca. SHP-77
0.0
CNS cancer (glio) SF-
0.0




295


Lung ca. A549
0.0
Brain (Amygdala)
12.9




Pool


Lung ca. NCI-H526
0.0
Brain (cerebellum)
3.2


Lung ca. NCI-H23
0.0
Brain (fetal)
12.9


Lung ca. NCI-H460
0.0
Brain (Hippocampus)
6.0




Pool


Lung ca. HOP-62
0.0
Cerebral Cortex Pool
4.9


Lung ca. NCI-H522
0.0
Brain (Substantia
26.6




nigra) Pool


Liver
0.0
Brain (Thalamus) Pool
37.9


Fetal Liver
0.0
Brain (whole)
0.0


Liver ca. HepG2
0.0
Spinal Cord Pool
0.0


Kidney Pool
100.0
Adrenal Gland
0.0


Fetal Kidney
4.4
Pituitary gland Pool
0.0


Renal ca. 786-0
0.0
Salivary Gland
0.0


Renal ca. A498
0.0
Thyroid (female)
0.0


Renal ca. ACHN
0.0
Pancreatic ca.
6.5




CAPAN2


Renal ca. UO-31
0.0
Pancreas Pool
6.3










[2161]

1025





TABLE CXC










Panel 4.1D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3498, Run

Ag3498, Run


Tissue Name
169839576
Tissue Name
169839576













Secondary Th1 act
78.5
HUVEC IL-1beta
11.3


Secondary Th2 act
17.0
HUVEC IFN gamma
12.4


Secondary Tr1 act
17.9
HUVEC TNF alpha +
15.7




IFN gamma


Secondary Th1 rest
5.2
HUVEC TNF alpha +
12.5




IL4


Secondary Th2 rest
7.0
HUVEC IL-11
5.4


Secondary Tr1 rest
5.5
Lung Microvascular EC
17.2




none


Primary Th1 act
14.8
Lung Microvascular EC
7.6




TNF alpha + IL-1beta


Primary Th2 act
16.0
Microvascular Dermal
8.1




EC none


Primary Tr1 act
13.3
Microsvasular Dermal
8.0




EC TNF alpha + IL-1beta


Primary Th1 rest
8.2
Bronchial epithelium
5.3




TNF alpha + IL 1beta


Primary Th2 rest
7.1
Small airway epithelium
4.3




none


Primary Tr1 rest
8.1
Small airway epithelium
6.4




TNF alpha + IL-1beta


CD45RA CD4
15.8
Coronery artery SMC rest
5.8


lymphocyte act


CD45RO CD4
15.9
Coronery artery SMC
5.9


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
19.6
Astrocytes rest
6.2


Secondary CD8
14.0
Astrocytes TNF alpha +
4.6


lymphocyte rest

IL-1beta


Secondary CD8
9.7
KU-812 (Basophil) rest
34.4


lymphocyte act


CD4 lymphocyte none
4.3
KU-812 (Basophil)
31.9




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
6.1
CCD1106
28.9


CD95 CH11

(Keratinocytes) none


LAK cells rest
12.6
CCD1106
34.2




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
9.9
Liver cirrhosis
1.4


LAK cells IL-2 + IL-12
12.6
NCI-H292 none
9.3


LAK cells IL-2 + IFN
9.4
NCI-H292 IL-4
13.1


gamma


LAK cells IL-2 + IL-18
12.5
NCI-H292 IL-9
17.7


LAK cells
13.9
NCI-H292 IL-13
13.6


PMA/ionomycin


NK Cells IL-2 rest
15.5
NCI-H292 IFN gamma
22.2


Two Way MLR 3 day
13.0
HPAEC none
4.4


Two Way MLR 5 day
14.4
HPAEC TNF alpha + IL-
12.4




1beta


Two Way MLR 7 day
8.8
Lung fibroblast none
5.7


PBMC rest
6.6
Lung fibroblast TNF
14.6




alpha + IL-1beta


PBMC PWM
16.8
Lung fibroblast IL-4
8.8


PBMC PHA-L
15.1
Lung fibroblast IL-9
13.0


Ramos (B cell) none
13.0
Lung fibroblast IL-13
10.2


Ramos (B cell)
11.4
Lung fibroblast IFN
17.8


ionomycin

gamma


B lymphocytes PWM
13.7
Dermal fibroblast
9.8




CCD1070 rest


B lymphocytes CD40L
13.8
Dermal fibroblast
10.8


and IL-4

CCD1070 TNF alpha


EOL-1 dbcAMP
11.1
Dermal fibroblast
11.2




CCD1070 IL-1beta


EOL-1 dbcAMP
100.0
Dermal fibroblast IFN
19.8


PMA/ionomycin

gamma


Dendritic cells none
14.4
Dermal fibroblast IL-4
9.7


Dendritic cells LPS
9.8
Dermal Fibroblast rest
7.7


Dendritic cells anti-
13.2
Neutrophils TNFa + LPS
0.7


CD40


Monocytes rest
8.9
Neutrophils rest
1.1


Monocytes LPS
32.5
Colon
4.4


Macrophages rest
12.6
Lung
5.1


Macrophages LPS
17.3
Thymus
7.3


HUVEC none
6.2
Kidney
4.9


HUVEC starved
10.0










[2162] CNS_neurodegeneration_v1.0 Summary: Ag3498 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[2163] General_screening_panel_v1.4 Summary: Ag3498 The CG59619-01 gene is only expressed at detectable levels in the adult kidney (CT=34.2). Thus, expression of this gene can be used to distinguish kidney from the other samples on this panel. In addition, expression of this gene is much lower in fetal kidney (CT=38.7), suggesting that this gene can be used to distinguish between the fetal and adult source of this tissue. Furthermore, this gene is not expressed at detectable levels in renal cancer cell lines. Therefore, therapeutic modulation of this gene may be of use in the treatment of renal cell carcinoma.


[2164] Panel 4.1D Summary: Ag3498 Expression of the CG59619-01 gene is highest in activated eosinophils (CT=25.7), displaying 10-fold upregulation when compared to the control eosinophils. Therefore, therapies designed with the protein encoded for by this gene could block or inhibit inflammation or tissue damage due to eosinophil activation in response to asthma, ulcerative colitis and parasitic diseases.


[2165] The CG59619-01 gene is expressed at moderate levels in the majority of samples on this panel, including T cells, B cells, endothelial cells, macrophages, monocytes, dendritic cells, basophils and peripheral blood mononuclear cells, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.


[2166] CY. CG59621-01: Selenide, Water Dikinase 1


[2167] Expression of gene CG59621-01 was assessed using the primer-probe set Ag3764, described in Table CYA.
1026TABLE CYAProbe Name Ag3764StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-catgttcagcctcatgcat-3′19925713ProbeTET-5′-agacctcaggcggccttctgatct-3′-TAMRA24957714Reverse5′-ctgcttgctgacatggtaaac-3′21981715


[2168] General_screening_panel_v1.4 Summary: Ag3764 Results from one experiment with the CG59621-01 gene are not included. The amp plot indicates that there were experimental difficulties with this run.


[2169] Panel 4.1D Summary: Ag3764 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel (data not shown).


[2170] CZ. CG59625-01: Glucose Transporter Type 3


[2171] Expression of gene CG59625-01 was assessed using the primer-probe set Ag3499, described in Table CZA. Results of the RTQ-PCR runs are shown in Tables CZB and CZC.
1027TABLE CZAProbe Name Ag3499StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-cttcccctctgctgcttactat-3′221298716ProbeTET-5′-ttttattatcttcaccggcttcctca-3′-TAMRA261334717Reverse5′-gaaggtaaaggccaagaaggta-3′221361718


[2172]

1028





TABLE CZB










CNS_neurodegeneration_v1.0











Rel.

Rel.



Exp. (%)

Exp. (%)



Ag3499,
Ag3499,



Run

Run


Tissue Name
210935864
Tissue Name
210935864













AD 1 Hippo
5.8
Control (Path) 3
4.9




Temporal Ctx


AD 2 Hippo
25.9
Control (Path) 4
32.3




Temporal Ctx


AD 3 Hippo
5.8
AD 1 Occipital
11.6




Ctx


AD 4 Hippo
1.5
AD 2 Occipital
0.0




Ctx (Missing)


AD 5 hippo
100.0
AD 3 Occipital
5.1




Ctx


AD 6 Hippo
29.7
AD 4 Occipital
4.5




Ctx


Control 2 Hippo
31.9
AD 5 Occipital
39.2




Ctx


Control 4 Hippo
0.0
AD 6 Occipital
72.2




Ctx


Control (Path) 3
6.6
Control 1 Occipital
13.5


Hippo

Ctx


AD 1 Temporal Ctx
7.0
Control 2 Occipital
82.4




Ctx


AD 2 Temporal Ctx
49.3
Control 3 Occipital
8.8




Ctx


AD 3 Temporal Ctx
2.9
Control 4 Occipital
0.0




Ctx


AD 4 Temporal Ctx
5.6
Control (Path) 1
64.6




Occipital Ctx


AD 5 Inf Temporal
83.5
Control (Path) 2
4.0


Ctx

Occipital Ctx


AD 5 SupTemporal
37.6
Control (Path) 3
4.0


Ctx

Occipital Ctx


AD 6 Inf Temporal
23.0
Control (Path) 4
13.2


Ctx

Occipital Ctx


AD 6 Sup Temporal
24.8
Control 1 Parietal
9.9


Ctx

Ctx


Control 1 Temporal
11.0
Control 2 Parietal
33.2


Ctx

Ctx


Control 2 Temporal
50.7
Control 3 Parietal
12.1


Ctx

Ctx


Control 3 Temporal
6.0
Control (Path) 1
57.8


Ctx

Parietal Ctx


Control 4 Temporal
0.1
Control (Path) 2
25.2


Ctx

Parietal Ctx


Control (Path) 1
28.9
Control (Path) 3
5.6


Temporal Ctx

Parietal Ctx


Control (Path) 2
13.9
Control (Path) 4
60.3


Temporal Ctx

Parietal Ctx










[2173]

1029





TABLE CZC










Panel 4D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3499, Run

Ag3499, Run


Tissue Name
166441940
Tissue Name
166441940













Secondary Th1 act
12.1
HUVEC IL-1beta
0.1


Secondary Th2 act
3.2
HUVEC IFN gamma
3.2


Secondary Tr1 act
3.6
HUVEC TNF alpha +
0.1




IFN gamma


Secondary Th1 rest
7.5
HUVEC TNF alpha +
0.0




IL4


Secondary Th2 rest
5.3
HUVEC IL-11
0.9


Secondary Tr1 rest
6.0
Lung Microvascular EC
2.0




none


Primary Th1 act
2.4
Lung Microvascular EC
1.2




TNF alpha + IL-1beta


Primary Th2 act
7.5
Microvascular Dermal
0.1




EC none


Primary Tr1 act
10.1
Microsvasular Dermal
0.1




EC TNF alpha + IL-1beta


Primary Th1 rest
14.9
Bronchial epithelium
0.3




TNF alpha + IL-1beta


Primary Th2 rest
5.1
Small airway epithelium
0.3




none


Primary Tr1 rest
5.8
Small airway epithelium
1.9




TNF alpha + IL1beta


CD45RA CD4
2.9
Coronery artery SMC rest
2.4


lymphocyte act


CD45RO CD4
12.3
Coronery artery SMC
1.3


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
4.1
Astrocytes rest
0.3


Secondary CD8
4.3
Astrocytes TNF alpha +
0.5


lymphocyte rest

IL-1beta


Secondary CD8
2.9
KU-812 (Basophil) rest
0.0


lymphocyte act


CD4 lymphocyte none
3.2
KU-812 (Basophil)
0.3




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
6.4
CCD1106
1.9


CD95 CH11

(Keratinocytes) none


LAK cells rest
8.9
CCD1106
30.6




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
14.1
Liver cirrhosis
19.2


LAK cells IL-2 + IL-12
7.1
Lupus Kidney
1.5


LAK cells IL-2 + IFN
8.2
NCI-H292 none
0.5


gamma


LAK cells IL-2 + IL-18
6.3
NCI-H292 IL-4
0.8


LAK cells
100.0
NCI-H292 IL-9
0.2


PMA/ionomycin


NK Cells IL-2 rest
4.8
NCI-H292 IL-13
0.3


Two Way MLR 3 day
7.4
NCI-H292 IFN gamma
0.2


Two Way MLR 5 day
7.6
HPAEC none
1.7


Two Way MLR 7 day
3.8
HPAEC TNF alpha + IL-
1.5




1beta


PBMC rest
0.1
Lung fibroblast none
3.2


PBMC PWM
10.9
Lung fibroblast TNF
2.7




alpha + IL-1beta


PBMC PHA-L
9.2
Lung fibroblast IL-4
4.7


Ramos (B cell) none
0.3
Lung fibroblast IL-9
2.4


Ramos (B cell)
0.2
Lung fibroblast IL-13
3.0


ionomycin


B lymphocytes PWM
3.8
Lung fibroblast IFN
5.5




gamma


B lymphocytes CD40L
2.6
Dermal fibroblast
3.7


and IL-4

CCD1070 rest


EOL-1 dbcAMP
0.1
Dermal fibroblast
15.1




CCD1070 TNF alpha


EOL-1 dbcAMP
0.6
Dermal fibroblast
2.5


PMA/ionomycin

CCD1070 IL-1beta


Dendritic cells none
30.4
Dermal fibroblast IFN
0.1




gamma


Dendritic cells LPS
14.2
Dermal fibroblast IL-4
0.1


Dendritic cells anti-
15.1
IBD Colitis 2
0.0


CD40


Monocytes rest
5.8
IBD Crohn's
1.1


Monocytes LPS
12.1
Colon
3.3


Macrophages rest
0.3
Lung
7.9


Macrophages LPS
12.9
Thymus
0.6


HUVEC none
0.1
Kidney
9.4


HUVEC starved
0.1










[2174] CNS_neurodegeneration_v1.0 Summary: Ag3499 This panel confirms the expression of this gene at moderate levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.


[2175] Panel 4D Summary: Ag3499 Expression of the CG59625-01 gene is highest in PMA/ionomycin-treated lymphokine activated killer (LAK) cells (CT=24.3). Since these cells are involved in tumor immunology and tumor cell clearance, as well as virally and bacterial infected cells, therapeutic modulation of this gene product may alter the functions of these cells and lead to improvement in cancer cell killing as well as host immunity to microbial and viral infections.


[2176] This gene is also expressed at high levels in stimulated keratinocytes, dendritic cells, monocytes and macrophages, suggesting that small molecule therapeutics designed against the CG59625-01 protein could reduce or inhibit inflammation in asthma, emphysema, allergy, psoriasis, arthritis, or any other condition in which localizalion/activation of these cell types is important.


[2177] This gene is also expressed at moderate levels in a number of other cell types of significance in the immune response in health and disease.


[2178] DA. CG59887-01 and CG59887-02: Amino Acid/Metabolite Permease


[2179] Expression of gene CG59887-01 and full length clone CG59887-02 was assessed using the primer-probe set Ag4715, described in Table DAA. Please note that CG59887-02 represents a full-length physical clone of the CG59887-02 gene, validating the prediction of the gene sequence.
1030TABLE DAAProbe Name Ag4715StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-cgtgttgtggtggttgtttt-3′201362719ProbeTET-5′-actgcgcacgcgccttaacaatg-3′-TAMRA231383720Reverse5′-ggctagtggtcgagcaattt-3′201426721


[2180] General_screening_panel_v1.4 Summary: Ag4715 Expression of the CG59887-01 gene is low/undetectable in all samples on this panel (CTs>35). (Data not shown.) The amp plot indicates that there is a high probability of a probe failure.


[2181] DB. CG59857-01: Rhotekin


[2182] Expression of gene CG59857-01 was assessed using the primer-probe set Ag3622, described in Table DBA. Results of the RTQ-PCR runs are shown in Tables DBB, DBC and DBD.
1031TABLE DBAProbe Name Ag3622StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-acatcctggaggacctgaatat-3′2284722ProbeTET-5′-ctctacattcggcagatggcactcag-3′-TAMRA26107723Reverse5′-ggatctcatggtctagcttcct-3′22155724


[2183]

1032





TABLE DBB










CNS_neurodegeneration_v1.0











Rel.

Rel.



Exp. (%)

Exp. (%)



Ag3622,

Ag3622,



Run

Run


Tissue Name
211005293
Tissue Name
211005293













AD 1 Hippo
10.7
Control (Path) 3
3.9




Temporal Ctx


AD 2 Hippo
42.9
Control (Path) 4
9.2




Temporal Ctx


AD 3 Hippo
6.9
AD 1 Occipital Ctx
10.1


AD 4 Hippo
13.2
AD 2 Occipital Ctx
0.0




(Missing)


AD 5 Hippo
40.6
AD 3 Occipital Ctx
7.1


AD 6 Hippo
38.4
AD 4 Occipital Ctx
23.3


Control 2 Hippo
29.9
AD 5 Occipital Ctx
28.5


Control 4 Hippo
13.6
AD 6 Occipital Ctx
0.1


Control (Path) 3
0.8
Control 1 Occipital
4.9


Hippo

Ctx


AD 1 Temporal
17.8
Control 2 Occipital
51.4


Ctx

Ctx


AD 2 Temporal
27.7
Control 3 Occipital
12.2


Ctx

Ctx


AD 3 Temporal
6.3
Control 4 Occipital
8.2


Ctx

Ctx


AD 4 Temporal
19.5
Control (Path) 1
58.6


Ctx

Occipital Ctx


AD 5 Inf Temporal
100.0
Control (Path) 2
10.2


Ctx

Occipital Ctx


AD 5 Sup
47.3
Control (Path) 3
5.7


Temporal Ctx

Occipital Ctx


AD 6 Inf Temporal
49.0
Control (Path) 4
7.9


Ctx

Occipital Ctx


AD 6 Sup
29.7
Control 1 Parietal
7.6


Temporal Ctx

Ctx


Control 1
5.6
Control 2 Parietal
44.4


Temporal Ctx

Ctx


Control 2
34.9
Control 3 Parietal
16.2


Temporal Ctx

Ctx


Control 3
13.7
Control (Path) 1
32.1


Temporal Ctx

Parietal Ctx


Control 3
8.2
Control (Path) 2
15.6


Temporal Ctx

Parietal Ctx


Control (Path) 1
18.8
Control (Path) 3
2.4


Temporal Ctx

Parietal Ctx


Control (Path) 2
16.0
Control (Path) 4
17.6


Temporal Ctx

Parietal Ctx










[2184]

1033





TABLE DBC










General_screening_panel_v1.4













Rel. Exp. (%)
Rel. Exp. (%)

Rel. Exp. (%)
Rel. Exp. (%)



Ag3622, Run
Ag3622, Run

Ag3622, Run
Ag3622, Run















Tissue Name
218211380
218307304
Tissue Name
218211380
218307304


Adipose
0.7
1.1
Renal ca. TK-10
4.7
4.0


Melanoma*
4.6
7.6
Bladder
10.2
3.5


Hs688(A).T


Melanoma*
7.2
6.4
Gastric ca. (liver
6.0
9.0


Hs688(B).T


met.) NCI-N87


Melanoma*
29.9
37.9
Gastric ca.
7.8
7.7


M14


KATO III


Melanoma*
15.1
17.2
Colon ca. SW-
1.9
1.3


LOXIMVI


948


Melanoma*
19.3
22.7
Colon ca.
11.0
15.1


SK-MEL-5


SW480


Squamous
0.4
1.5
Colon ca.*
5.9
10.4


cell


(SW480 met)


carcinoma


SW620


SCC-4


Testis Pool
2.0
1.7
Colon ca. HT29
5.4
6.8


Prostate ca.*
3.3
3.4
Colon ca. HCT-
5.6
6.7


(bone met)


116


PC-3


Prostate Pool
0.8
2.3
Colon ca. CaCo-2
4.2
3.2


Placenta
2.2
3.0
Colon cancer
2.3
3.5





tissue


Uterus Pool
0.8
0.7
Colon ca.
1.1
2.9





SW1116


Ovarian ca.
19.5
18.7
Colon ca. Colo-
1.0
0.3


OVCAR-3


205


Ovarian ca.
9.0
8.0
Colon ca. SW-48
1.2
1.2


SK-OV-3


Ovarian ca.
1.1
2.2
Colon Pool
16.0
5.8


OVCAR-4


Ovarian ca.
6.4
9.0
Small Intestine
1.7
3.3


OVCAR-5


Pool


Ovarian ca.
10.7
10.7
Stomach Pool
2.7
3.8


IGROV-1


Ovarian ca.
7.1
20.3
Bone Marrow
1.2
1.8


OVCAR-8


Pool


Ovary
3.2
4.3
Fetal Heart
5.1
6.5


Breast ca.
1.1
1.4
Heart Pool
1.5
3.0


MCF-7


Breast ca.
8.8
10.9
Lymph Node
4.9
6.5


MDA-MB-


Pool


231


Breast ca. BT
4.7
8.4
Fetal Skeletal
69.7
11.3


549


Muscle


Breast ca.
17.0
15.2
Skeletal Muscle
2.7
1.5


T47D


Pool


Breast ca.
23.8
21.0
Spleen Pool
2.8
1.8


MDA-N


Breast Pool
4.4
5.0
Thymus Pool
2.8
5.9


Trachea
3.8
5.8
CNS cancer
17.7
25.0





(glio/astro) U87-





MG


Lung
0.7
0.8
CNS cancer
46.0
57.4





(glio/astro) U-





118-MG


Fetal Lung
8.2
9.3
CNS cancer
26.8
35.6





(neuro; met) SK-





N-AS


Lung ca.
0.4
0.5
CNS cancer
9.7
9.8


NCI-N417


(astro) SF-539


Lung ca. LX-1
9.3
10.7
CNS cancer
22.5
34.4





(astro) SNB-75


Lung ca.
8.4
6.7
CNS cancer
9.0
13.0


NCI-H146


(glio) SNB-19


Lung ca.
7.4
6.4
CNS cancer
33.2
37.1


SHP-77


(glio) SF-295


Lung ca.
13.3
23.3
Brain
86.5
82.9


A549


(Amygdala) Pool


Lung ca.
1.3
1.4
Brain
22.5
30.8


NCI-H526


(cerebellum)


Lung ca.
5.1
6.0
Brain (fetal)
5.1
6.5


NCI-H23


Lung ca.
5.2
4.9
Brain
45.4
52.1


NCI-H460


(Hippocampus)





Pool


Lung ca.
5.1
7.4
Cerebral Cortex
27.4
40.3


HOP-62


Pool


Lung ca.
6.7
9.8
Brain (Substantia
46.7
54.7


NCI-H522


nigra) Pool


Liver
0.5
0.9
Brain
51.4
90.1





(Thalamus) Pool


Fetal Liver
1.7
1.5
Brain (whole)
23.8
32.8


Liver ca.
2.9
4.5
Spinal Cord Pool
100.0
100.0


HepG2


Kidney Pool
5.3
6.4
Adrenal Gland
1.5
3.5


Fetal Kidney
7.0
11.7
Pituitary gland
0.3
2.5





Pool


Renal ca.
2.8
3.0
Salivary Gland
1.4
3.2


786-0


Renal ca.
4.9
5.6
Thyroid (female)
2.8
2.1


A498


Renal ca.
4.2
4.0
Pancreatic ca.
1.7
0.6


ACHN


CAPAN2


Renal ca.
10.4
7.7
Pancreas Pool
5.2
6.2


UO-31










[2185]

1034





TABLE DBD










Panel 4.1D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3622, Run

Ag3622, Run


Tissue Name
169944131
Tissue Name
169944131













Secondary Th1 act
0.0
HUVEC IL-1beta
14.7


Secondary Th2 act
2.9
HUVEC IFN gamma
25.2


Secondary Tr1 act
7.3
HUVEC TNF alpha +
2.5




IFN gamma


Secondary Th1 rest
0.0
HUVEC TNF alpha +
5.8




IL4


Secondary Th2 rest
0.0
HUVEC IL-11
19.2


Secondary Tr1 rest
0.0
Lung Microvascular EC
49.0




none


Primary Th1 act
6.5
Lung Microvascular EC
11.3




TNF alpha + IL-1beta


Primary Th2 act
0.0
Microvascular Dermal
7.7




EC none


Primary Tr1 act
0.0
Microsvasular Dermal
10.9




EC TNF alpha + IL-1beta


Primary Th1 rest
0.0
Bronchial epithelium
21.5




TNF alpha + IL1beta


Primary Th2 rest
0.0
Small airway epithelium
7.2




none


Primary Tr1 rest
0.0
Small airway epithelium
27.9




TNF alpha + IL-1beta


CD45RA CD4
0.8
Coronery artery SMC rest
22.5


lymphocyte act


CD45RO CD4
3.5
Coronery artery SMC
31.4


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
1.8
Astrocytes rest
17.0


Secondary CD8
1.6
Astrocytes TNF alpha +
25.3


lymphocyte rest

IL-1beta


Secondary CD8
0.2
KU-812 (Basophil) rest
8.0


lymphocyte act


CD4 lymphocyte none
0.0
KU-812 (Basophil)
3.4




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
4.2
CCD1106
44.8


CD95 CH11

(Keratinocytes) none


LAK cells rest
0.4
CCD1106
61.6




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
6.0
Liver cirrhosis
0.0


LAK cells IL-2 + IL-12
0.0
NCI-H292 none
5.3


LAK cells IL-2 + IFN
1.5
NCI-H292 IL-4
9.9


gamma


LAK cells IL-2 + IL-18
0.0
NCI-H292 IL-9
14.4


LAK cells
0.0
NCI-H292 IL-13
1.4


PMA/ionomycin


NK Cells IL-2 rest
13.9
NCI-H292 IFN gamma
11.4


Two Way MLR 3 day
3.6
HPAEC none
20.9


Two Way MLR 5 day
3.8
HPAEC TNF alpha + IL-
10.2




1beta


Two Way MLR 7 day
0.0
Lung fibroblast none
38.2


PBMC rest
1.7
Lung fibroblast TNF
25.0




alpha + IL-1beta


PBMC PWM
3.6
Lung fibroblast IL-4
35.8


PBMC PHA-L
1.3
Lung fibroblast IL-9
100.0


Ramos (B cell) none
0.2
Lung fibroblast IL-13
69.7


Ramos (B cell)
1.1
Lung fibroblast IFN
58.2


ionomycin

gamma


B lymphocytes PWM
0.5
Dermal fibroblast
39.2




CCD1070 rest


B lymphocytes CD40L
7.9
Dermal fibroblast
5.7


and IL-4

CCD1070 TNF alpha


EOL-1 dbcAMP
0.0
Dermal fibroblast
17.4




CCD1070 IL-1beta


EOL-1 dbcAMP
0.0
Dermal fibroblast IFN
31.2


PMA/ionomycin

gamma


Dendritic cells none
9.9
Dermal fibroblast IL-4
44.8


Dendritic cells LPS
2.4
Dermal Fibroblasts rest
19.1


Dendritic cells anti-
24.7
Neutrophils TNFa + LPS
0.0


CD40


Monocytes rest
0.0
Neutrophils rest
0.0


Monocytes LPS
6.3
Colon
10.3


Macrophages rest
8.8
Lung
13.6


Macrophages LPS
3.4
Thymus
2.4


HUVEC none
11.1
Kidney
23.8


HUVEC starved
28.5










[2186] CNS_neurodegeneration_v1.0 Summary: Ag3622 This panel confirms the expression of the CG59857-01 gene at significant levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.


[2187] General_screening_panel_v1.4 Summary: Ag3622 Two experiments with the same probe and primer set show highest expression of the CG59857-01 gene in spinal cord samples (CTs=26-28). In addition, high levels of expression of this gene are seen in brain derived tissue, including samples from amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and CNS cancer cell lines. Therefore, expression of this gene could be used to distinguish between brain derived samples and other samples used in this panel. Furthermore, this gene may play a role in central nervous system disorders such as Alzheinier's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[2188] Significant expression is also detected in fetal skeletal muscle (CTs=27-31). Interestingly, this gene is expressed at much higher levels in fetal when compared to adult skeletal muscle (CTs=32-34). This observation suggests that expression of this gene can be used to distinguish fetal from adult skeletal muscle. In addition, the relative overexpression of this gene in fetal skeletal muscle suggests that the protein product may enhance muscular growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of muscle related diseases. More specifically, treatment of weak or dystrophic muscle with the protein encoded by this gene could restore muscle mass or function.


[2189] Among tissues with metabolic function, this gene is expressed at moderate to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.


[2190] Panel 4.1D Summary: Ag3622 Highest expression of the CG59857-01 gene is seen in IL-9/IL-13 treated lung fibroblasts (CT=31). In addition, significant expression is seen in clusters of treated and untreated lung and dermal fibroblasts, epithelium and endothelium. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, and psoriasis.


[2191] DC. CG59855-01 and CG59855-02: ATP Synthase Subunit C


[2192] Expression of gene CG59855-01 and full length clone CG59855-02 was assessed using the primer-probe set Ag3621, described in Table DCA. Results of the RTQ-PCR runs are shown in Tables DCB and DCC. Please note that CG59855-02 represents a full-length physical clone of the CG59855-02 gene, validating the prediction of the gene sequence.
1035TABLE DCAProbe Name Ag3621StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-gggtctaatcaggcctgtgt-3′2073725ProbeTET-5′-tgccttctccttgaatagcccagaga-3′-TAMRA2694726Reverse5′-ctgctgtaggaaggctgtttag-3′22126727


[2193]

1036





TABLE DCB










General_screening_panel_v1.4











Rel. Exp.

Rel. Exp.



(%) Ag3621,

(%) Ag3621,



Run

Run


Tissue Name
217702346
Tissue Name
217702346













Adipose
0.0
Renal ca. TK-10
0.0


Melanoma*
0.0
Bladder
7.5


Hs688(A).T


Melanoma*
0.0
Gastric ca. (liver met.)
0.0


Hs688(B).T

NCI-N87


Melanoma* M14
0.0
Gastric ca. KATO III
0.0


Melanoma*
0.0
Colon ca. SW-948
0.0


LOXIMVI


Melanoma* SK-
0.0
Colon ca. SW480
0.0


MEL-5


Squamous cell
0.0
Colon ca.* (SW480
0.0


carcinoma SCC-4

met) SW620


Testis Pool
35.1
Colon ca. HT29
0.0


Prostate ca.* (bone
0.0
Colon ca. HCT-116
0.0


met) PC-3


Prostate Pool
3.5
Colon ca. CaCo-2
0.0


Placenta
2.9
Colon cancer tissue
0.0


Uterus Pool
5.9
Colon ca. SW1116
0.0


Ovarian ca.
0.0
Colon ca. Colo-205
0.0


OVCAR-3


Ovarian ca. SK-
47.6
Colon ca. SW-48
0.0


OV-3


Ovarian ca.
0.0
Colon Pool
57.0


OVCAR-4


Ovarian ca.
0.0
Small Intestine Pool
42.9


OVCAR-5


Ovarian ca.
0.0
Stomach Pool
7.5


IGROV-1


Ovarian ca.
0.0
Bone Marrow Pool
7.0


OVCAR-8


Ovary
12.9
Fetal Heart
0.0


Breast ca. MCF-7
0.0
Heart Pool
0.0


Breast ca. MDA-
0.0
Lymph Node Pool
8.1


MB-231


Breast ca. BT 549
0.0
Fetal Skeletal Muscle
13.2


Breast ca. T47D
0.0
Skeletal Muscle Pool
0.0


Breast ca. MDA-N
0.0
Spleen Pool
27.4


Breast Pool
49.0
Thymus Pool
25.9


Trachea
46.3
CNS cancer
0.0




(glio/astro) U87-MG


Lung
38.4
CNS cancer
0.0




(glio/astro) U-118-MG


Fetal Lung
100.0
CNS cancer
0.0




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.0
CNS cancer (astro)
0.0




SF-539


Lung ca. LX-1
0.0
CNS cancer (astro)
0.0




SNB-75


Lung ca. NCI-H146
0.0
CNS cancer (glio)
0.0




SNB-19


Lung ca. SHP-77
0.0
CNS cancer (glio)
0.0




SF-295


Lung ca. A549
0.0
Brain (Amygdala)
0.0




Pool


Lung ca. NCI-H526
0.0
Brain (cerebellum)
0.0


Lung ca. NCI-H23
6.7
Brain (fetal)
0.0


Lung ca. NCI-H460
0.0
Brain (Hippocampus)
0.0




Pool


Lung ca. HOP-62
0.0
Cerebral Cortex Pool
0.0


Lung ca. NCI-H522
0.0
Brain (Substantia
0.0




nigra) Pool


Liver
0.0
Brain (Thalamus) Pool
0.0


Fetal Liver
0.0
Brain (whole)
0.0


Liver ca. HepG2
0.0
Spinal Cord Pool
6.1


Kidney Pool
57.8
Adrenal Gland
0.0


Fetal Kidney
10.7
Pituitary gland Pool
12.4


Renal ca. 786-0
0.0
Salivary Gland
0.0


Renal ca. A498
0.0
Thyroid (female)
0.0


Renal ca. ACHN
0.0
Pancreatic ca.
0.0




CAPAN2


Renal ca. UO-31
0.0
Pancreas Pool
63.3










[2194]

1037





TABLE DCC










Panel 4.1D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3621, Run

Ag3621, Run


Tissue Name
169944096
Tissue Name
169944096













Secondary Th1 act
1.0
HUVEC IL-1beta
0.0


Secondary Th2 act
0.0
HUVEC IFN gamma
1.0


Secondary Tr1 act
16.5
HUVEC TNF alpha +
0.0




IFN gamma


Secondary Th1 rest
7.5
HUVEC TNF alpha +
0.0




IL4


Secondary Th2 rest
2.6
HUVEC IL-11
7.8


Secondary Tr1 rest
0.0
Lung Microvascular EC
1.0




none


Primary Th1 act
0.0
Lung Microvascular EC
6.7




TNF alpha + IL-1beta


Primary Th2 act
0.0
Microvascular Dermal
0.0




EC none


Primary Tr1 act
0.0
Microsvasular Dermal
0.0




EC TNF alpha + IL-1beta


Primary Th1 rest
0.0
Bronchial epithelium
0.0




TNF alpha + IL-1beta


Primary Th2 rest
1.5
Small airway epithelium
0.0




none


Primary Tr1 rest
0.0
Small airway epithelium
0.0




TNF alpha + IL-1beta


CD45RA CD4
0.0
Coronery artery SMC rest
0.0


lymphocyte act


CD45RO CD4
0.0
Coronery artery SMC
0.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
0.0
Astrocytes rest
1.1


Secondary CD8
0.0
Astrocytes TNF alpha +
0.9


lymphocyte rest

IL-1beta


Secondary CD8
0.0
KU-812 (Basophil) rest
0.0


lymphocyte act


CD4 lymphocyte none
8.6
KU-812 (Basophil)
0.0




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
0.0
CCD1106
0.0


CD95 CH11

(Keratinocytes) none


LAK cells rest
0.0
CCD1106
0.0




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
0.0
Liver cirrhosis
0.0


LAK cells IL-2 + IL-12
0.0
NCI-H292 none
4.5


LAK cells IL-2 + IFN
0.0
NCI-H292 IL-4
0.0


gamma


LAK cells IL-2 + IL-18
0.0
NCI-H292 IL-9
1.5


LAK cells
2.3
NCI-H292 IL-13
0.0


PMA/ionomycin


NK Cells IL-2 rest
0.0
NCI-H292 IFN gamma
0.0


Two Way MLR 3 day
1.3
HPAEC none
2.9


Two Way MLR 5 day
0.0
HPAEC TNF alpha + IL-
2.3




1beta


Two Way MLR 7 day
0.9
Lung fibroblast none
5.1


PBMC rest
1.0
Lung fibroblast TNF
0.0




alpha + IL-1beta


PBMC PWM
0.0
Lung fibroblast IL-4
0.0


PBMC PHA-L
0.0
Lung fibroblast IL-9
0.0


Ramos (B cell) none
0.0
Lung fibroblast IL-13
0.0


Ramos (B cell)
0.0
Lung fibroblast IFN
0.0


ionomycin

gamma


B lymphocytes PWM
0.0
Dermal fibroblast
9.0




CCD1070 rest


B lymphocytes CD40L
0.0
Dermal fibroblast
1.1


and IL-4

CCD1070 TNF alpha


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0




CCD1070 IL-1beta


EOL-1 dbcAMP
0.0
Dermal fibroblast IFN
0.0


PMA/ionomycin

gamma


Dendritic cells none
2.0
Dermal fibroblast IL-4
2.8


Dendritic cells LPS
17.6
Dermal Fibroblasts rest
0.0


Dendritic cells anti-
2.7
Neutrophils TNFa + LPS
0.0


CD40


Monocytes rest
100.0
Neutrophils rest
20.0


Monocytes LPS
6.1
Colon
0.8


Macrophages rest
2.8
Lung
0.0


Macrophages LPS
0.0
Thymus
0.0


HUVEC none
0.0
Kidney
9.3


HUVEC starved
0.0










[2195] CNS_neurodegeneration_v1.0 Summary: Ag3621 Expression of the CG59855-01 gene is low/undetectable in all samples on this panel (CTs>35). (Data not shown.)


[2196] General_screening_panel_v1.4 Summary: Ag3621 Expression of the CG59855-01 gene is restricted to samples from fetal lung and adult pancrease(CTs=34.5-35). Thus, expression of this gene can be used to distinguish this sample from other samples in the panel.


[2197] The CG59855-01 gene encodes a homologue of ATP synthase subunit c, mitochondrial precursor. Subunit c is an intrinsic membrane component of ATP synthase, and in mammals it is encoded by two expressed nuclear genes, P1 and P2. Both genes encode the same mature c subunit, but the mitochondrial import pre-sequences in the precursors of subunit c are different (ref. 1). Each ATP synthase complex has multiple copies of subunit C. The mitochondrial ATP synthase uses energy derived from a proton gradient to synthesize ATP. The structure of this complex has been referred to as a ‘lollipop,’ as the soluble F1 catalytic unit is attached to the mitochondrial inner membrane via the F0 unit containing subunit c. F0 subunit C transports protons across the mitochondrial inner membrane to the F1-ATPase (ref. 2).


[2198] Subunit C of the F0 region of the ATP synthase complex of the inner mitochondrial membrane is found in high concentrations in lysosomes in late infantile neuronal ceroid lipofuscinosis (Batten's disease). Kominami et al. (1995, Ref 3) found marked delay of degradation of subunit C in patient fibroblasts with no significant differences between control and patient cells with regard to degradation of cytochrome oxidase subunit IV. Furthermore, accumulation of labeled subunit C in the mitochondrial fraction was detected before Lysosomal appearance of the radiolabeled subunit, suggesting to the authors a specific failure in the degradation of subunit C after its normal inclusion in mitochondria and its consequent accumulation in lysosomes. Jolly (1995, ref 4) reported that subunit C represents more than 50% of the accumulated metabolites in the ovine form of the disease and also accumulates significantly in late infantile and juvenile forms of the human disease and several other animal forms. The author suggested that the extreme hydrophobicity and lipophilicity of subunit C may be in part responsible.



REFERENCES

[2199] 1. Dyer M R, Walker J E. (1993) Sequences of members of the human gene family for the c subunit of mitochondrial ATP synthase. Biochem J 293 (Pt 1):51-64


[2200] 2. OMIM 603192


[2201] 3. Kominami E, Ezaki J, Wolfe L S. (1995) New insight into lysosomal protein storage disease: delayed catabolism of ATP synthase subunit c in Batten disease. Neuroctiem Res 20(11):1305-9


[2202] 4. Jolly R D. (1995) Batten disease (ceroid-lipofuscinosis): the enigma of subunit c of mitochondrial ATP synthase accumulation. Neurochem Res 20(11):1301-4


[2203] Panel 4.1D Summary: Ag3621 Expression of the CG59855-01 gene is exclusively seen in resting monocytes (CT=32). Thus, expression of this gene can be used to distinguish this sample from other samples in the panel. In addition, expression of this gene in monocytes suggests a role for the gene product in their function as antigen-presenting cells. This suggests that antibodies or small molecule therapeutics that block the function of this protein nay be useful as anti-inflammatory therapeutics for the treatment of autoimmune and inflammatory diseases and for the treatment of immunosupressed individuals.


[2204] DD. CG59807-01: Nuclear Hormone Receptor/Zinc Finger


[2205] Expression of gene CG59807-01 was assessed using the primer-probe set Ag3591, described in Table DDA. Results of the RTQ-PCR runs are shown in Tables DDB and DDC.
1038TABLE DDAProbe Name Ag3591StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-cactgctccacttttgtcttg-3′211195728ProbeTET-5′-cataaaaggacccacacaggagaaaa-3′-TAMRA261216729Reverse5′-cttttccacattctttgcattc-3′221249730


[2206]

1039





TABLE DDB










General_screening_panel_v1.4











Rel. Exp.

Rel. Exp.



(%) Ag3591,

(%) Ag3591,



Run

Run


Tissue Name
217479278
Tissue Name
217479278













Adipose
13.9
Renal ca. TK-10
22.2


Melanoma*
18.6
Bladder
27.5


Hs688(A).T


Melanoma*
17.6
Gastric ca. (liver met.)
100.0


Hs688(B).T

NCI-N87


Melanoma* M14
22.8
Gastric ca. KATO III
63.7


Melanoma*
12.5
Colon ca. SW-948
4.9


LOXIMVI


Melanoma* SK-
10.4
Colon ca. SW480
41.2


MEL-5


Squamous cell
27.9
Colon ca.* (SW480
17.1


carcinoma SCC-4

met) SW620


Testis Pool
14.9
Colon ca. HT29
19.3


Prostate ca.* (bone
51.4
Colon ca. HCT-116
52.9


met) PC-3


Prostate Pool
12.7
Colon ca. CaCo-2
13.5


Placenta
8.7
Colon cancer tissue
7.4


Uterus Pool
5.0
Colon ca. SW1116
11.3


Ovarian ca.
29.9
Colon ca. Colo-205
8.3


OVCAR-3


Ovarian ca. SK-
49.7
Colon ca. SW-48
3.2


OV-3


Ovarian ca.
9.1
Colon Pool
18.8


OVCAR-4


Ovarian ca.
14.6
Small Intestine Pool
19.2


OVCAR-5


Ovarian ca.
26.2
Stomach Pool
15.1


IGROV-1


Ovarian ca.
14.4
Bone Marrow Pool
7.5


OVCAR-8


Ovary
12.7
Fetal Heart
24.5


Breast ca. MCF-7
9.5
Heart Pool
10.9


Breast ca. MDA-
42.0
Lymph Node Pool
33.9


MB-231


Breast ca. BT 549
66.0
Fetal Skeletal Muscle
24.0


Breast ca. T47D
40.3
Skeletal Muscle Pool
19.9


Breast ca. MDA-N
13.7
Spleen Pool
30.4


Breast Pool
25.5
Thymus Pool
30.6


Trachea
14.5
CNS cancer
19.2




(glio/astro) U87-MG


Lung
14.6
CNS cancer
51.1




(glio/astro) U-118-MG


Fetal Lung
72.7
CNS cancer
49.0




(neuro; met) SK-N-AS


Lung ca. NCI-N417
2.6
CNS cancer (astro)
18.7




SF-539


Lung ca. LX-1
21.2
CNS cancer (astro)
48.6




SNB-75


Lung ca. NCI-H146
24.5
CNS cancer (glio)
26.6




SNB-19


Lung ca. SHP-77
33.7
CNS cancer (glio)
80.1




SF-295


Lung ca. A549
16.6
Brain (Amygdala)
10.6




Pool


Lung ca. NCI-H526
14.7
Brain (cerebellum)
65.5


Lung ca. NCI-H23
35.4
Brain (fetal)
50.0


Lung ca. NCI-H460
33.0
Brain (Hippocampus)
15.3




Pool


Lung ca. HOP-62
10.4
Cerebral Cortex Pool
18.6


Lung ca. NCI-H522
30.6
Brain (Substantia
19.9




nigra) Pool


Liver
2.0
Brain (Thalamus) Pool
26.6


Fetal Liver
21.6
Brain (whole)
25.9


Liver ca. HepG2
16.4
Spinal Cord Pool
16.3


Kidney Pool
27.7
Adrenal Gland
25.0


Fetal Kidney
28.1
Pituitary gland Pool
8.2


Renal ca. 786-0
25.2
Salivary Gland
7.0


Renal ca. A498
12.9
Thyroid (female)
9.2


Renal ca. ACHN
23.5
Pancreatic ca.
12.5




CAPAN2


Renal ca. UO-31
32.1
Pancreas Pool
16.8










[2207]

1040





TABLE DDC










Panel 4.1D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3591, Run

Ag3591, Run


Tissue Name
169908857
Tissue Name
169908857













Secondary Th1 act
38.4
HUVEC IL-1beta
24.7


Secondary Th2 act
37.4
HUVEC IFN gamma
23.5


Secondary Tr1 act
48.6
HUVEC TNF alpha +
17.3




IFN gamma


Secondary Th1 rest
22.7
HUVEC TNF alpha +
20.6




IL4


Secondary Th2 rest
34.9
HUVEC IL-11
19.6


Secondary Tr1 rest
35.1
Lung Microvascular EC
36.6




none


Primary Th1 act
47.0
Lung Microvascular EC
39.5




TNF alpha + IL-1beta


Primary Th2 act
43.5
Microvascular Dermal
22.1




EC none


Primary Tr1 act
50.3
Microsvasular Dermal
21.9




EC TNF alpha + IL-1beta


Primary Th1 rest
43.5
Bronchial epithelium
35.4




TNF alpha + IL-1beta


Primary Th2 rest
40.6
Small airway epithelium
14.0




none


Primary Tr1 rest
51.1
Small airway epithelium
31.0




TNF alpha + IL-1beta


CD45RA CD4
22.2
Coronery artery SMC rest
14.5


lymphocyte act


CD45RO CD4
38.4
Coronery artery SMC
12.0


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
39.8
Astrocytes rest
24.1


Secondary CD8
22.5
Astrocytes TNF alpha +
20.0


lymphocyte rest

IL-1beta


Secondary CD8
31.0
KU-812 (Basophil) rest
57.8


lymphocyte act


CD4 lymphocyte none
15.8
KU-812 (Basophil)
98.6




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
57.8
CCD1106
28.7


CD95 CH11

(Keratinocytes) none


LAK cells rest
28.9
CCD1106
24.1




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
44.4
Liver cirrhosis
8.6


LAK cells IL-2 + IL-12
35.4
NCI-H292 none
40.1


LAK cells IL-2 + IFN
44.8
NCI-H292 IL-4
80.7


gamma


LAK cells IL-2 + IL-18
52.5
NCI-H292 IL-9
79.0


LAK cells
18.3
NCI-H292 IL-13
100.0


PMA/ionomycin


NK Cells IL-2 rest
44.1
NCI-H292 IFN gamma
100.0


Two Way MLR 3 day
42.0
HPAEC none
21.6


Two Way MLR 5 day
25.7
HPAEC TNF alpha + IL-
32.8




1beta


Two Way MLR 7 day
20.4
Lung fibroblast none
28.5


PBMC rest
11.2
Lung fibroblast TNF
13.9




alpha + IL-1beta


PBMC PWM
21.3
Lung fibroblast IL-4
28.1


PBMC PHA-L
24.7
Lung fibroblast IL-9
49.3


Ramos (B cell) none
61.1
Lung fibroblast IL-13
37.9


Ramos (B cell)
66.9
Lung fibroblast IFN
29.5


ionomycin

gamma


B lymphocytes PWM
24.1
Dermal fibroblast
29.9




CCD1070 rest


B lymphocytes CD40L
56.6
Dermal fibroblast
45.1


and IL-4

CCD1070 TNF alpha


EOL-1 dbcAMP
69.7
Dermal fibroblast
11.0




CCD1070 IL-1beta


EOL-1 dbcAMP
54.0
Dermal fibroblast IFN
8.7


PMA/ionomycin

gamma


Dendritic cells none
26.6
Dermal fibroblast IL-4
29.7


Dendritic cells LPS
10.2
Dermal Fibroblast rest
12.2


Dendritic cells anti-
23.2
Neutrophils TNFa + LPS
1.3


CD40


Monocytes rest
12.2
Neutrophils rest
3.3


Monocytes LPS
16.5
Colon
8.8


Macrophages rest
18.6
Lung
33.4


Macrophages LPS
8.1
Thymus
82.9


HUVEC none
17.4
Kidney
23.8


HUVEC starved
27.2










[2208] General_screening_panel_v1.4 Summary: Ag3591 Highest expression of the CG59807-01 gene is detected in the gastric cancer cell line (CT=28). In addition, high expression of this gene is seen in samples derived from CNS cancer, colon cancer, breast cancer, ovarian cancer, prostate cancer cell lines (CTs=28-31). Therefore, therapeutic modulation of the activity of this gene or its protein product, through the use of small molecule drugs, protein therapeutics or antibodies, might be beneficial in the treatment of these cancers.


[2209] In addition, expression of this gene is higher in fetal liver (CT=31) as compared to the corresponding adult tissues (CTs=34). Thus, expression of this gene can be used to distinguish between the fetal and adults source of this tissue.


[2210] Among tissues with metabolic or endocrine function, this gene is expressed at high to moderate levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.


[2211] This gene is also expressed at high levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[2212] Panel 4.1D Summary: Ag3591 Highest expression of the CG59807-01 gene is detected in treated mucoepidermoid NCI-H292 cells. In addition, this gene is expressed at high to moderate levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.5 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.


[2213] DE. CG59805-01: Nuclear Hormone Receptor/Zinc Finger


[2214] Expression of gene CG59805-01 was assessed using the primer-probe set Ag3590, described in Table DEA. Results of the RTQ-PCR runs are shown in Tables DEB, DEC and DED.
1041TABLE DEAProbe Name Ag3590StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-atgagtgcagtgaatgtggaa-3′211620731ProbeTET-5′-cttcagtcgcagctcgtccctcact-3′-TAMRA251645732Reverse5′-atttctcccagtatgcatcctt-3′221678733


[2215]

1042





TABLE DEB










CNS_neurodegeneration_v1.0











Rel. Exp.

Rel. Exp.



(%) Ag3590,

(%) Ag3590,



Run

Run


Tissue Name
211006692
Tissue Name
211006692













AD 1 Hippo
16.7
Control (Path) 3
5.8




Temporal Ctx


AD 2 Hippo
22.1
Control (Path) 4
42.6




Temporal Ctx


AD 3 Hippo
8.2
AD 1 Occipital Ctx
17.7


AD 4 Hippo
7.9
AD 2 Occipital Ctx
0.0




(Missing)


AD 5 Hippo
73.2
AD 3 Occipital Ctx
3.9


AD 6 Hippo
87.7
AD 4 Occipital Ctx
23.3


Control 2 Hippo
25.7
AD 5 Occipital Ctx
32.5


Control 4 Hippo
17.0
AD 6 Occipital Ctx
31.2


Control (Path) 3
7.4
Control 1 Occipital
5.2


Hippo

Ctx


AD 1 Temporal
25.2
Control 2 Occipital
39.2


Ctx

Ctx


AD 2 Temporal
34.2
Control 3 Occipital
20.0


Ctx

Ctx


AD 3 Temporal
10.1
Control 4 Occipital
8.1


Ctx

Ctx


AD 4 Temporal
28.3
Control (Path) 1
80.7


Ctx

Occipital Ctx


AD 5 Inf Temporal
71.7
Control (Path) 2
11.1


Ctx

Occipital Ctx


AD 5 Sup
35.4
Control (Path) 3
6.1


Temporal Ctx

Occipital Ctx


AD 6 Inf Temporal
98.6
Control (Path) 4
17.9


Ctx

Occipital Ctx


AD 6 Sup
100.0
Control 1 Parietal
8.8


Temporal Ctx

Ctx


Control 1
8.2
Control 2 Parietal
39.0


Temporal Ctx

Ctx


Control 2
29.1
Control 3 Parietal
18.3


Temporal Ctx

Ctx


Control 3
17.3
Control (Path) 1
55.5


Temporal Ctx

Parietal Ctx


Control 3
10.2
Control (Path) 2
26.8


Temporal Ctx

Parietal Ctx


Control (Path) 1
50.7
Control (Path) 3
7.4


Temporal Ctx

Parietal Ctx


Control (Path) 2
34.6
Control (Path) 4
46.0


Temporal Ctx

Parietal Ctx










[2216]

1043





TABLE DEC










General_screening_panel_v1.4











Rel. Exp.

Rel. Exp.



(%) Ag3590,

(%) Ag3590,



Run

Run


Tissue Name
217474417
Tissue Name
217474417













Adipose
12.8
Renal ca. TK-10
28.9


Melanoma*
33.7
Bladder
28.5


Hs688(A).T


Melanoma*
25.3
Gastric ca. (liver met.)
82.4


Hs688(B).T

NCI-N87


Melanoma* M14
16.3
Gastric ca. KATO III
24.5


Melanoma*
19.6
Colon ca. SW-948
5.8


LOXIMVI


Melanoma* SK-
16.5
Colon ca. SW480
28.1


MEL-5


Squamous cell
29.5
Colon ca.* (SW480
10.7


carcinoma SCC-4

met) SW620


Testis Pool
16.0
Colon ca. HT29
13.6


Prostate ca.* (bone
57.4
Colon ca. HCT-116
26.2


met) PC-3


Prostate Pool
14.6
Colon ca. CaCo-2
28.5


Placenta
7.7
Colon cancer tissue
13.0


Uterus Pool
6.0
Colon ca. SW1116
4.8


Ovarian ca.
18.9
Colon ca. Colo-205
3.4


OVCAR-3


Ovarian ca. SK-
38.2
Colon ca. SW-48
2.3


OV-3


Ovarian ca.
15.4
Colon Pool
27.0


OVCAR-4


Ovarian ca.
17.4
Small Intestine Pool
24.1


OVCAR-5


Ovarian ca.
12.2
Stomach Pool
14.3


IGROV-1


Ovarian ca.
12.5
Bone Marrow Pool
11.7


OVCAR-8


Ovary
14.2
Fetal Heart
21.8


Breast ca. MCF-7
29.1
Heart Pool
10.7


Breast ca. MDA-
28.3
Lymph Node Pool
29.5


MB-231


Breast ca. BT 549
100.0
Fetal Skeletal Muscle
10.7


Breast ca. T47D
34.4
Skeletal Muscle Pool
14.7


Breast ca. MDA-N
12.5
Spleen Pool
26.2


Breast Pool
40.6
Thymus Pool
26.8


Trachea
16.3
CNS cancer
32.3




(glio/astro) U87-MG


Lung
4.6
CNS cancer
57.0




(glio/astro) U-118-MG


Fetal Lung
66.4
CNS cancer
33.2




(neuro; met) SK-N-AS


Lung ca. NCI-N417
2.0
CNS cancer (astro)
14.4




SF-539


Lung ca. LX-1
15.9
CNS cancer (astro)
46.7




SNB-75


Lung ca. NCI-H146
3.3
CNS cancer (glio)
14.9




SNB-19


Lung ca. SHP-77
24.5
CNS cancer (glio)
82.9




SF-295


Lung ca. A549
17.2
Brain (Amygdala)
7.2




Pool


Lung ca. NCI-H526
5.4
Brain (cerebellum)
13.2


Lung ca. NCI-H23
26.4
Brain (fetal)
26.8


Lung ca. NCI-H460
22.5
Brain (Hippocampus)
10.3




Pool


Lung ca. HOP-62
10.6
Cerebral Cortex Pool
14.6


Lung ca. NCI-H522
18.9
Brain (Substantia
13.9




nigra) Pool


Liver
1.6
Brain (Thalamus) Pool
18.2


Fetal Liver
26.1
Brain (whole)
16.5


Liver ca. HepG2
19.8
Spinal Cord Pool
9.1


Kidney Pool
43.5
Adrenal Gland
30.8


Fetal Kidney
26.2
Pituitary gland Pool
7.3


Renal ca. 786-0
26.1
Salivary Gland
7.7


Renal ca. A498
19.8
Thyroid (female)
6.5


Renal ca. ACHN
14.6
Pancreatic ca.
13.3




CAPAN2


Renal ca. UO-31
27.0
Pancreas Pool
25.2










[2217]

1044





TABLE DED










Panel 4.1D











Rel. Exp. (%)

Rel. Exp. (%)



Ag3590, Run

Ag3590, Run


Tissue Name
169908854
Tissue Name
169908854













Secondary Th1 act
33.9
HUVEC IL-1beta
31.0


Secondary Th2 act
42.6
HUVEC IFN gamma
30.6


Secondary Tr1 act
52.1
HUVEC TNF alpha +
18.9




IFN gamma


Secondary Th1 rest
20.3
HUVEC TNF alpha +
18.2




IL4


Secondary Th2 rest
28.1
HUVEC IL-11
17.4


Secondary Tr1 rest
26.6
Lung Microvascular EC
39.5




none


Primary Th1 act
44.1
Lung Microvascular EC
54.0




TNF alpha + IL-1beta


Primary Th2 act
38.7
Microvascular Dermal
25.9




EC none


Primary Tr1 act
45.7
Microsvasular Dermal
36.6




EC TNF alpha + IL-1beta


Primary Th1 rest
23.3
Bronchial epithelium
51.1




TNF alpha + IL-1beta


Primary Th2 rest
27.7
Small airway epithelium
22.1




none


Primary Tr1 rest
30.4
Small airway epithelium
33.0




TNF alpha + IL-1beta


CD45RA CD4
24.8
Coronery artery SMC rest
38.4


lymphocyte act


CD45RO CD4
42.9
Coronery artery SMC
29.1


lymphocyte act

TNF alpha + IL-1beta


CD8 lymphocyte act
39.2
Astrocytes rest
34.9


Secondary CD8
32.8
Astrocytes TNF alpha +
26.2


lymphocyte rest

IL-1beta


Secondary CD8
19.5
KU-812 (Basophil) rest
56.6


lymphocyte act


CD4 lymphocyte none
37.4
KU-812 (Basophil)
100.0




PMA/ionomycin


2ry Th1/Th2/Tr1_anti-
39.8
CCD1106
29.3


CD95 CH11

(Keratinocytes) none


LAK cells rest
43.8
CCD1106
34.9




(Keratinocytes)




TNF alpha + IL-1beta


LAK cells IL-2
38.2
Liver cirrhosis
12.9


LAK cells IL-2 + IL-12
39.5
NCI-H292 none
22.2


LAK cells IL-2 + IFN
50.3
NCI-H292 IL-4
38.7


gamma


LAK cells IL-2 + IL-18
51.1
NCI-H292 IL-9
41.2


LAK cells
50.0
NCI-H292 IL-13
36.1


PMA/ionomycin


NK Cells IL-2 rest
41.5
NCI-H292 IFN gamma
56.3


Two Way MLR 3 day
50.7
HPAEC none
19.3


Two Way MLR 5 day
28.5
HPAEC TNF alpha + IL-
50.3




1beta


Two Way MLR 7 day
19.5
Lung fibroblast none
37.6


PBMC rest
33.2
Lung fibroblast TNF
24.0




alpha + IL-1beta


PBMC PWM
25.7
Lung fibroblast IL-4
49.3


PBMC PHA-L
16.3
Lung fibroblast IL-9
56.6


Ramos (B cell) none
42.3
Lung fibroblast IL-13
43.5


Ramos (B cell)
33.4
Lung fibroblast IFN
42.9


ionomycin

gamma


B lymphocytes PWM
24.3
Dermal fibroblast
38.7




CCD1070 rest


B lymphocytes CD40L
36.9
Dermal fibroblast
43.8


and IL-4

CCD1070 TNF alpha


EOL-1 dbcAMP
40.3
Dermal fibroblast
22.8




CCD1070 IL-1beta


EOL-1 dbcAMP
37.9
Dermal fibroblast IFN
12.3


PMA/ionomycin

gamma


Dendritic cells none
33.7
Dermal fibroblast IL-4
55.1


Dendritic cells LPS
18.9
Dermal Fibroblasts rest
23.2


Dendritic cells anti-
26.8
Neutrophils TNFa + LPS
1.4


CD40


Monocytes rest
33.7
Neutrophils rest
16.5


Monocytes LPS
31.4
Colon
8.8


Macrophages rest
19.8
Lung
41.2


Macrophages LPS
6.6
Thymus
82.9


HUVEC none
16.0
Kidney
30.8


HUVEC starved
20.0










[2218] CNS_neurodegeneration_v1.0 Summary: Ag3590 This panel confirms the expression of the CG59805-01 gene at low levels in the brain in an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.


[2219] General_screening_panel_v1.4 Summary: Ag3590 Highest expression of the CG59805-01 gene is detected in one of the breast cancer cell line BT 549 (CT=26). In addition, expression of this gene is high in CNS cancer, gastric cancer, and prostate cancer cell lines. Therefore, expression of this gene can be used to distinguish these samples from other samples in this panel and it can be used as marker for detection of these cancers. Furthermore, therapeutic modulation of the activity of the protein encoded by this gene may be beneficial in the treatment of these cancers.


[2220] Among tissues with metabolic or endocrine function, this gene is expressed at high to moderate levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases. such as obesity and diabetes.


[2221] In addtion, this gene is expressed at high levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.


[2222] Panel 4.1D Summary: Ag3590 Highest expression of the CG59805-01 gene is detected in PMA/ionomycin treated Ku-812 (basophil) cells (CT=29). In addition, this gene is expressed at high to moderate levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.4 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.


[2223] DF. CG59928-01: Novel Universal Stress (USP) Domain Containg Protein


[2224] Expression of gene CG59928-01 was assessed using the primer-probe set Ag3636, described in Table DFA. Please note that this sequence is represented by a full length clone.
1045TABLE DFAProbe Name Ag3636StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-gaagccttcgacaagctgat-3′201268734ProbeTET-5′-atcgatagagcacaggcccacctgtt-3′-TAMRA261301735Reverse5′-gatgacttcctcggcaaaac-3′201332736


[2225] CNS_neurodegeneration_v1.0 Summary: Ag3636 Expression of the CG59928-01 gene is low/undetectable in all samples on this panel (CTs>35). (Data not shown.) The amp plot indicates that there is a high probability of a probe failure.


[2226] General_screening_panel_v1.4 Summary: Ag3636 Expression of the CG59928-01 gene is low/undetectable in all samples on this panel (CTs>35). (Data not shown.) The amp plot indicates that there is a high probability of a probe failure.


[2227] Panel 4.1D Summary: Ag3636 Expression of the CG59928-01 gene is low/undetectable in all samples on this panel (CTs>35). (Data not shown.) The amp plot indicates that there is a high probability of a probe failure.


[2228] DG. CG59947-01: Voltage-Gated Potassium Channel Protein KV3.3


[2229] Expression of gene CG59947-01 was assessed using the primer-probe set Ag3635, described in Table DGA. Results of the RTQ-PCR runs are shown in Tables DGB, DGC, DGD and DGE.
1046TABLE DGAProbe Name Ag3635StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-tacttcaagaacatccccattg-3′221326737ProbeTET-5′-ctgtggtcaccatgacgaccctg-3′-TAMRA231360738Reverse5′-tcttggggtacatgtctccata-3′221386739


[2230]

1047





TABLE DGB










CNS_neurodegeneration_v1.0











Rel. Exp.

Rel. Exp.



(%) Ag3635,

(%) Ag3635,



Run

Run


Tissue Name
211020704
Tissue Name
211020704













AD 1 Hippo
8.7
Control (Path) 3
2.8




Temporal Ctx


AD 2 Hippo
14.3
Control (Path) 4
23.8




Temporal Ctx


AD 3 Hippo
5.1
AD 1 Occipital
0.9




Ctx


AD 4 Hippo
4.8
AD 2 Occipital
0.0




Ctx (Missing)


AD 5 hippo
100.0
AD 3 Occipital
4.2




Ctx


AD 6 Hippo
23.7
AD 4 Occipital
13.0




Ctx


Control 2 Hippo
22.4
AD 5 Occipital
18.4




Ctx


Control 4 Hippo
4.9
AD 6 Occipital
47.3




Ctx


Control (Path) 3
2.7
Control 1 Occipital
2.0


Hippo

Ctx


AD 1 Temporal Ctx
6.8
Control 2 Occipital
99.3




Ctx


AD 2 Temporal Ctx
18.3
Control 3 Occipital
11.3




Ctx


AD 3 Temporal Ctx
4.6
Control 4 Occipital
2.6




Ctx


AD 4 Temporal Ctx
11.5
Control (Path) 1
80.7




Occipital Ctx


AD 5 Inf Temporal
68.8
Control (Path) 2
10.4


Ctx

Occipital Ctx


AD 5 SupTemporal
23.5
Control (Path) 3
2.5


Ctx

Occipital Ctx


AD 6 Inf Temporal
21.6
Control (Path) 4
18.4


Ctx

Occipital Ctx


AD 6 Sup Temporal
31.0
Control 1 Parietal
3.9


Ctx

Ctx


Control 1 Temporal
3.8
Control 2 Parietal
20.2


Ctx

Ctx


Control 2 Temporal
30.8
Control 3 Parietal
20.3


Ctx

Ctx


Control 3 Temporal
8.3
Control (Path) 1
66.4


Ctx

Parietal Ctx


Control 4 Temporal
4.9
Control (Path) 2
21.2


Ctx

Parietal Ctx


Control (Path) 1
46.7
Control (Path) 3
1.8


Temporal Ctx

Parietal Ctx


Control (Path) 2
16.8
Control (Path) 4
51.4


Temporal Ctx

Parietal Ctx










[2231]

1048





TABLE DGC










Panel 2.2











Rel. Exp.

Rel. Exp.



(%) Ag3635,

(%) Ag3635,



Run

Run


Tissue Name
173764364
Tissue Name
173764364













Normal Colon
5.4
Kidney Margin
100.0




(OD04348)


Colon cancer
5.0
Kidney malignant
5.0


(OD06064)

cancer (OD06204B)


Colon Margin
3.0
Kidney normal
19.2


(OD06064)

adjacent tissue




(OD06204E)


Colon cancer
1.0
Kidney Cancer
5.7


(OD06159)

(OD04450-01)


Colon Margin
2.8
Kidney Margin
23.3


(OD06159)

(OD04450-03)


Colon cancer
2.0
Kidney Cancer
1.2


(OD06297-04)

8120613


Colon Margin
5.0
Kidney Margin
23.5


(OD06297-05)

8120614


CC Gr.2 ascend colon
4.4
Kidney Cancer
3.6


(ODO3921)

9010320


CC Margin
0.7
Kidney Margin
12.9


(ODD3921)

9010321


Colon cancer
1.8
Kidney Cancer
13.3


metastasis (OD06104)

8120607


Lung Margin
0.6
Kidney Margin
16.3


(OD06104)

8120608


Colon mets to lung
1.6
Normal Uterus
6.3


(OD04451-01)


Lung Margin
6.1
Uterine Cancer
20.3


(OD04451-02)

064011


Normal Prostate
8.2
Normal Thyroid
6.7


Prostate Cancer
2.2
Thyroid Cancer
4.8


(OD04410)

064010


Prostate Margin
3.4
Thyroid Cancer
33.7


(OD04410)

A302152


Normal Ovary
5.4
Thyroid Margin
7.0




A302153


Ovarian cancer
9.9
Normal Breast
23.7


(OD06283-03)


Ovarian Margin
5.6
Breast Cancer
3.2


(OD06283-07)

(OD04566)


Ovarian Cancer
8.0
Breast Cancer 1024
63.3


064008


Ovarian cancer
13.1
Breast Cancer
8.7


(OD06145)

(OD04590-01)


Ovarian Margin
15.7
Breast Cancer Mets
4.0


(OD06145)

(OD04590-03)


Ovarian cancer
24.7
Breast Cancer
78.5


(OD06455-03)

Metastasis




(OD04655-05)


Ovarian Margin
3.5
Breast Cancer
16.3


(OD06455-07)

064006


Normal Lung
8.2
Breast Cancer
5.2




9100266


Invasive poor diff.
5.4
Breast Margin
5.4


lung adeno

9100265


(ODO4945-01)


Lung Margin
7.7
Breast Cancer
2.2


(ODO4945-03)

A209073


Lung Malignant
3.7
Breast Margin
20.3


Cancer (OD03126)

A2090734


Lung Margin
3.1
Breast cancer
9.1


(OD03126)

(OD06083)


Lung Cancer
8.8
Breast cancer node
7.6


(OD05014A)

metastasis




(OD06083)


Lung Margin
12.6
Normal Liver
7.4


(OD05014B)


Lung cancer
11.0
Liver Cancer 1026
4.5


(OD06081)


Lung Margin
6.7
Liver Cancer 1025
9.7


(OD06081)


Lung Cancer
1.0
Liver Cancer
7.4


(OD04237-01)

6004-T


Lung Margin
10.4
Liver Tissue
7.4


(OD04237-02)

6004-N


Ocular Melanoma
5.1
Liver Cancer
5.2


Metastasis

6005-T


Ocular Melanoma
6.1
Liver Tissue
8.8


Margin (Liver)

6005-N


Melanoma Metastasis
1.6
Liver Cancer
5.9




064003


Melanoma Margin
5.1
Normal Bladder
6.1


(Lung)


Normal Kidney
11.3
Bladder Cancer
4.6




1023


Kidney Ca, Nuclear
51.8
Bladder Cancer
7.9


grade 2 (OD04338)

A302173


Kidney Margin
4.7
Normal Stomach
8.6


(OD04338)


Kidney Ca Nuclear
24.5
Gastric Cancer
1.2


grade 1/2 (OD04339)

9060397


Kidney Margin
21.5
Stomach Margin
4.3


(OD04339)

9060396


Kidney Ca, Clear cell
2.3
Gastric Cancer
1.9


type (OD04340)

9060395


Kidney Margin
14.8
Stomach Margin
6.8


(OD04340)

9060394


Kidney Ca, Nuclear
1.1
Gastric Cancer
3.1


grade 3 (OD04348)

064005










[2232]

1049





TABLE DGE










Panel CNS_1











Rel. Exp. (%)

Rel. Exp.



Ag3635, Run

Ag3635, Run


Tissue Name
171648701
Tissue Name
171648701













BA4 Control
16.7
BA17 PSP
27.0


BA4 Control2
39.2
BA17 PSP2
8.9


BA4
5.0
Sub Nigra Control
1.1


Alzheimer's2


BA4 Parkinson's
28.5
Sub Nigra Control2
16.5


BA4
100.0
Sub Nigra
4.1


Parkinson's2

Alzheimer's2


BA4
24.7
Sub Nigra
26.1


Huntington's

Parkinson's2


BA4
9.7
Sub Nigra
25.3


Huntington's2

Huntington's


BA4 PSP
11.7
Sub Nigra
9.3




Huntington's2


BA4 PSP2
36.6
Sub Nigra PSP2
2.4


BA4 Depression
14.9
Sub Nigra
2.0




Depression


BA4
8.8
Sub Nigra
4.5


Depression2

Depression2


BA7 Control
25.3
Glob Palladus
3.3




Control


BA7 Control2
42.6
Glob Palladus
4.9




Control2


BA7
4.5
Glob Palladus
4.5


Alzheimer's2

Alzheimer's


BA7 Parkinson's
10.4
Glob Palladus
1.2




Alzheimer's2


BA7
29.5
Glob Palladus
21.6


Parkinson's2

Parkinson's


BA7
25.3
Glob Palladus
2.0


Huntington's

Parkinson's2


BA7
12.9
Glob Palladus PSP
1.6


Huntington's2


BA7 PSP
30.6
Glob Palladus PSP2
2.1


BA7 PSP2
12.1
Glob Palladus
1.4




Depression


BA7 Depression
10.1
Temp Pole Control
7.3


BA9 Control
15.0
Temp Pole Control2
27.4


BA9 Control2
47.0
Temp Pole
4.2




Alzheimer's


BA9 Alzheimer's
4.7
Temp Pole
2.5




Alzheimer's2


BA9
9.2
Temp Pole
15.1


Alzheimer's2

Parkinson's


BA9 Parkinson's
28.9
Temp Pole
14.2




Parkinson's2


BA9
34.4
Temp Pole
19.2


Parkinson's2

Huntington's


BA9
24.1
Temp Pole PSP
3.4


Huntington's


BA9
9.5
Temp Pole PSP2
3.0


Huntington's2


BA9 PSP
10.2
Temp Pole
4.8




Depression2


BA9 PSP2
6.2
Cing Gyr Control
20.9


BA9 Depression
5.6
Cing Gyr Control2
25.9


BA9
8.3
Cing Gyr
5.6


Depression2

Alzheimer's


BA17 Control
33.2
Cing Gyr
6.3




Alzheimer's2


BA17 Control2
64.6
Cing Gyr
9.1




Parkinson's


BA17
7.2
Cing Gyr
13.1


Alzheimer's2

Parkinson's2


BA17
18.3
Cing Gyr
22.1


Parkinson's

Huntington's


BA17
35.1
Cing Gyr
6.0


Parkinson's2

Huntington's2


BA17
32.1
Cing Gyr PSP
6.5


Huntington's


BA17
8.8
Cing Gyr PSP2
2.6


Huntington's2


BA17
7.3
Cing Gyr
2.6


Depression

Depression


BA17
25.7
Cing Gyr
6.1


Depression2

Depression2










[2233] CNS_neurodegeneration_v1.0 Summary: Ag3635 This panel confirms the expression of CG59947-01 gene at low levels in the brain in an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. This gene encodes a potassium channel protein homolog. The significant levels of expression in the brain may indicate a role for this protein in signal processing in the central nervous system.



REFERENCES

[2234] 1. Rudy B, Chow A, Lau D, Amarillo Y, Ozaita A, Saganich M, Moreno H, Nadal M S, Hernandez-Pineda R, Hernandez-Cruz A, Erisir A, Leonard C, Vega-Saenz de Miera E.


[2235] 2. Contributions of Kv3 channels to neuronal excitability. Ann NY Acad Sci Apr. 30, 1999;868:304-43


[2236] General_screening_panel_v1.4 Summary: Ag3635 Results from one experiment with the CG59947-01 gene are not included. The amp plot indicates that there were experimental difficulties with this run.


[2237] Panel 2.2 Summary: Ag3635 Highest expression of the CG59447-01 gene is seen in normal kidney tissue adjacent to a tumor (CT=28). In addition, expression appears to be higher in normal kidney tissue than in the adjacent tumor in six out of nine matched pairs. Conversely expression appears to be higher in breast cancer than in matched normal breast tissue. Thus, expression of this gene could be used to differentiate between these samples and other samples on this panel and as a marker for kidney and breast cancers. Furthermore, therapeutic modulation of the expression or function of this protein may be effective in the treatment of breast and kidney cancer.


[2238] Panel 4.1D Summary: Ag3635 This gene is expressed at high to moderate levels in a wide range of cell types of significance in the immune response in health and disease, with highest expression in anti CD40 dendritic cells (CT=28.1). Other cells that express this protein include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.


[2239] Panel CNS1 Summary: Ag3635 Expression in this panel confirms expression of the CG59947-01 gene in the brain. Please see Panel CNS_neurodegeneration_v1.0 for discussion of utility of this gene in the central nervous system.


[2240] DH. CG59938-01: Arylsulfatase


[2241] Expression of gene CG59938-01 was assessed using the primer-probe set Ag3634, described in Table DHA.
1050TABLE DHAProbe Name Ag3634StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-agccaatgaaagaggagaaagt-3′22870740ProbeTET-5′-cttccctcatgctgaaggaggcactt-3′-TAMRA26894741Reverse5′-cccttttgtacctttcaatgaa-3′22923742


[2242] CNS_neurodegeneration_v1.0 Summary: Ag3634 Expression of the CG55938-01 gene is low/undetectable in all samples on this panel (CTs>35). (Data not shown.)


[2243] General_screening_panel_v1.4 Summary: Ag3634 Expression of the CG55938-01 gene is low/undetectable in all samples on this panel (CTs>35). (Data not shown.)


[2244] Panel 2.2 Summary: Ag3634 Expression of the CG55938-01 gene is low/undetectable in all samples on this panel (CTs>35). (Data not shown.)


[2245] Panel 4.1D Summary: Ag3634 Expression of the CG55938-01 gene is low/undetectable in all samples on this panel (CTs>35). (Data not shown.)


[2246] DI. CG!59746-01: Ubiquitin Carboxyl-Terminal Hydrolase


[2247] Expression of gene CG59746-01 was assessed using the primer-probe set Ag3574, described in Table DIA.
1051TABLE DIAProbe Name Ag3574StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-agcacaacacagaaggaaatca-3′22461743ProbeTET-5′-tcattccacaaagttgatgagaaatca-3′-TAMRA27491744Reverse5′-gtcccacttccttttgctatct-3′22534745


[2248] CNS_neurodegeneration_v1.0 Summary: Ag3574 Expression of the CG59746-01 gene is low/undetectable in all samples on this panel (CTs>35). (Data not shown.)


[2249] General_screening_panel_v1.4 Summary: Ag3574 Expression of the CG59746-01 gene is low/undetectable in all samples on this panel (CTs>35). (Data not shown.)


[2250] Panel 2.2 Summary: Ag3574 Expression of the CG59746-01 gene is low/undetectable in all samples on this panel (CTs>35). (Data not shown.)


[2251] Panel 4.1D Summary: Ag3574 Expression of the CG59746-01 gene is low/undetectable in all samples on this panel (CTs>35). (Data not shown.)


[2252] Panel CNS1 Summary: Ag3574 Expression of the CG59746-01 gene is low/undetectable in all samples on this panel (CTs>35). (Data not shown.)


[2253] DJ. CG8613-01: Inositol 1,4,5-Trisphosphate 3-Kinase Isoenzyme


[2254] Expression of gene CG88613-01 was assessed using the primer-probe set Ag3647, described in Table DJA. Results of the RTQ-PCR runs are shown in Tables DJB, DJC and DJD.
1052TABLE DJAProbe Name Ag3647StartSEQ IDPrimerSequencesLengthPositionNO:Forward5′-actggagcaggtgacaaaagt-3′211731766ProbeTET-5′-accacgtcatcctgcaaaagtacgtg-3′-TAMRA261775767Reverse5′-cagagcttcacgaagttcttct-3′221809768


[2255]

1053





TABLE DJB










CNS_neurodegeneration_v1.0











Rel. Exp.

Rel. Exp.



(%) Ag3647,

(%) Ag3647,



Run

Run


Tissue Name
211019283
Tissue Name
211019283













AD 1 Hippo
44.8
Control (Path) 3
16.3




Temporal Ctx


AD 2 Hippo
28.1
Control (Path) 4
20.7




Temporal Ctx


AD 3 Hippo
10.2
AD 1 Occipital
30.1




Ctx


AD 4 Hippo
10.7
AD 2 Occipital
0.0




Ctx (Missing)


AD 5 hippo
98.6
AD 3 Occipital
17.1




Ctx


AD 6 Hippo
75.3
AD 4 Occipital
17.9




Ctx


Control 2 Hippo
33.4
AD 5 Occipital
39.8




Ctx


Control 4 Hippo
29.1
AD 6 Occipital
42.6




Ctx


Control (Path) 3
14.9
Control 1 Occipital
8.0


Hippo

Ctx


AD 1 Temporal Ctx
19.5
Control 2 Occipital
67.4




Ctx


AD 2 Temporal Ctx
29.1
Control 3 Occipital
29.3




Ctx


AD 3 Temporal Ctx
14.2
Control 4 Occipital
16.6




Ctx


AD 4 Temporal Ctx
23.8
Control (Path) 1
57.4




Occipital Ctx


AD 5 Inf Temporal
100.0
Control (Path) 2
12.9


Ctx

Occipital Ctx


AD 5 SupTemporal
69.7
Control (Path) 3
14.6


Ctx

Occipital Ctx


AD 6 Inf Temporal
73.2
Control (Path) 4
12.5


Ctx

Occipital Ctx


AD 6 Sup Temporal
57.8
Control 1 Parietal
11.7


Ctx

Ctx


Control 1 Temporal
17.3
Control 2 Parietal
50.0


Ctx

Ctx


Control 2 Temporal
47.6
Control 3 Parietal
39.0


Ctx

Ctx


Control 3 Temporal
32.5
Control (Path) 1
41.8


Ctx

Parietal Ctx


Control 4 Temporal
20.9
Control (Path) 2
18.4


Ctx

Parietal Ctx


Control (Path) 1
35.6
Control (Path) 3
16.0


Temporal Ctx

Parietal Ctx


Control (Path) 2
28.3
Control (Path) 4
20.4


Temporal Ctx

Parietal Ctx










[2256]

1054





TABLE DJC










General_screening_panel_v1.4











Rel. Exp.

Rel. Exp.



(%) Ag3647,

(%) Ag3647,



Run

Run


Tissue Name
218342103
Tissue Name
218342103













Adipose
37.9
Renal ca. TK-10
23.3


Melanoma*
15.7
Bladder
24.1


Hs688(A).T


Melanoma*
20.2
Gastric ca. (liver met.)
100.0


Hs688(B).T

NCI-N87


Melanoma* M14
11.3
Gastric ca. KATO III
25.2


Melanoma*
8.5
Colon ca. SW-948
11.2


LOXIMVI


Melanoma* SK-
13.0
Colon ca. SW480
38.7


MEL-5


Squamous cell
35.6
Colon ca.* (SW480
11.7


carcinoma SCC-4

met) SW620


Testis Pool
6.4
Colon ca. HT29
17.2


Prostate ca.* (bone
11.7
Colon ca. HCT-116
24.1


met) PC-3


Prostate Pool
12.7
Colon ca. CaCo-2
78.5


Placenta
31.6
Colon cancer tissue
37.1


Uterus Pool
4.5
Colon ca. SW1116
8.0


Ovarian ca.
21.2
Colon ca. Colo-205
4.6


OVCAR-3


Ovarian ca. SK-
22.2
Colon ca. SW-48
9.3


OV-3


Ovarian ca.
22.2
Colon Pool
13.5


OVCAR-4


Ovarian ca.
32.5
Small Intestine Pool
13.0


OVCAR-5


Ovarian ca.
32.8
Stomach Pool
11.7


IGROV-1


Ovarian ca.
14.3
Bone Marrow Pool
5.7


OVCAR-8


Ovary
7.9
Fetal Heart
5.0


Breast ca. MCF-7
50.0
Heart Pool
6.4


Breast ca. MDA-
25.7
Lymph Node Pool
11.2


MB-231


Breast ca. BT 549
61.1
Fetal Skeletal Muscle
4.4


Breast ca. T47D
87.7
Skeletal Muscle Pool
11.6


Breast ca. MDA-N
7.4
Spleen Pool
6.0


Breast Pool
10.6
Thymus Pool
8.3


Trachea
24.5
CNS cancer
14.9




(glio/astro) U87-MG


Lung
3.5
CNS cancer
16.6




(glio/astro) U-118-MG


Fetal Lung
95.3
CNS cancer
15.7




(neuro; met) SK-N-AS


Lung ca. NCI-N417
3.9
CNS cancer (astro)
11.3




SF-539


Lung ca. LX-1
16.4
CNS cancer (astro)
34.4




SNB-75


Lung ca. NCI-H146
6.0
CNS cancer (glio)
48.0




SNB-19


Lung ca. SHP-77
23.3
CNS cancer (glio)
45.4




SF-295


Lung ca. A549
25.0
Brain (Amygdala)
12.6




Pool


Lung ca. NCI-H526
6.4
Brain (cerebellum)
37.1


Lung ca. NCI-H23
10.2
Brain (fetal)
13.6


Lung ca. NCI-H460
8.7
Brain (Hippocampus)
15.3




Pool


Lung ca. HOP-62
11.3
Cerebral Cortex Pool
15.6


Lung ca. NCI-H522
16.8
Brain (Substantia
27.0




nigra) Pool


Liver
2.5
Brain (Thalamus) Pool
17.0


Fetal Liver
6.6
Brain (whole)
8.9


Liver ca. HepG2
16.3
Spinal Cord Pool
19.9


Kidney Pool
24.0
Adrenal Gland
9.9


Fetal Kidney
8.0
Pituitary gland Pool
6.3


Renal ca. 786-0
11.4
Salivary Gland
7.2


Renal ca. A498
21.2
Thyroid (female)
12.1


Renal ca. ACHN
10.2
Pancreatic ca.
35.1




CAPAN2


Renal ca. UO-31
18.3
Pancreas Pool
23.3










[2257]

1055





TABLE DJD










Panel 4.1D













Rel.
Rel.

Rel.
Rel.



Exp. (%)
Exp. (%)

Exp. (%)
Exp. (%)



Ag3647,
Ag3647,

Ag3647,
Ag3647,



Run
Run

Run
Run


Tissue Name
169975750
197444046
Tissue Name
169975750
197444046















Secondary Th1 act
7.7
7.1
HUVEC IL-1beta
20.4
22.1


Secondary Th2 act
10.7
8.7
HUVEC IFN
21.5
21.6





gamma


Secondary Tr1 act
9.1
7.9
HUVEC TNF
39.2
26.2





alpha + IFN





gamma


Secondary Th1 rest
4.2
2.7
HUVEC TNF
20.9
16.6





alpha + IL4


Secondary Th2 rest
6.0
6.2
HUVEC IL-11
8.5
8.8


Secondary Tr1 rest
5.0
4.0
Lung
29.9
31.0





Microvascular EC





none


Primary Th1 act
8.1
6.3
Lung
37.4
24.1





Microvascular EC





TNF alpha + IL-





1beta


Primary Th2 act
9.0
9.5
Microvascular
17.9
12.4





Dermal EC none


Primary Tr1 act
10.1
10.7
Microsvasular
20.0
15.6





Dermal EC





TNF alpha + IL-





1beta


Primary Th1 rest
6.0
2.3
Bronchial
41.5
34.6





epithelium





TNF alpha +





IL-1beta


Primary Th2 rest
4.3
1.1
Small airway
37.4
33.2





epithelium none


Primary Tr1 rest
7.4
5.4
Small airway
58.2
43.8





epithelium





TNF alpha + IL-





1beta


CD45RA CD4
4.2
4.2
Coronery artery
6.3
8.0


lymphocyte act


SMC rest


CD45RO CD4
7.1
5.7
Coronery artery
9.7
7.8


lymphocyte act


SMC TNF alpha +





IL-1beta


CD8 lymphocyte
6.2
4.5
Astrocytes rest
11.7
4.2


act


Secondary CD8
9.7
8.5
Astrocytes
11.1
7.2


lymphocyte rest


TNF alpha + IL-





1beta


Secondary CD8
6.5
3.7
KU-812
10.0
7.9


lymphocyte act


(Basophil) rest


CD4 lymphocyte
1.8
1.7
KU-812
14.4
13.3


none


(Basophil)





PMA/ionomycin


2ry
3.1
2.9
CCD1106
42.0
46.7


Th1/Th2/Tr1_anti-


(Keratinocytes)


CD95 CH11


none


LAK cells rest
9.9
5.9
CCD1106
100.0
100.0





(Keratinocytes)





TNF alpha + IL-





1beta


LAK cells IL-2
5.3
4.5
Liver cirrhosis
14.7
16.2


LAK cells IL-
9.2
3.2
NCI-H292 none
17.1
16.2


2 + IL-12


LAK cells IL-
6.1
3.8
NCI-H292 IL-4
19.1
25.0


2 + IFN gamma


LAK cells IL-2 +
11.3
5.5
NCI-H292 IL-9
25.7
23.8


IL-18


LAK cells
20.9
16.2
NCI-H292 IL-13
20.6
18.8


PMA/ionomycin


NK Cells IL-2 rest
8.2
12.1
NCI-H292 IFN
42.6
28.3





gamma


Two Way MLR 3
9.2
11.4
HPAEC none
13.6
11.7


day


Two Way MLR 5
8.4
4.9
HPAEC TNF
20.3
22.1


day


alpha + IL-1beta


Two Way MLR 7
8.7
5.8
Lung fibroblast
16.4
17.3


day


none


PBMC rest
3.0
2.2
Lung fibroblast
11.6
13.6





TNF alpha + IL-





1beta


PBMC PWM
11.0
7.6
Lung fibroblast
14.6
28.3





IL-4


PBMC PHA-L
9.1
4.6
Lung fibroblast
16.3
23.8





IL-9


Ramos (B cell)
5.2
3.6
Lung fibroblast
14.7
12.9


none


IL-13


Ramos (B cell)
5.1
4.9
Lung fibroblast
22.7
23.8


ionomycin


IFN gamma


B lymphocytes
4.1
3.8
Dermal fibroblast
12.0
13.6


PWM


CCD1070 rest


B lymphocytes
8.4
4.9
Dermal fibroblast
10.9
14.7


CD40L and IL-4


CCD1070 TNF





alpha


EOL-1 dbcAMP
7.3
5.5
Dermal fibroblast
10.0
4.4





CCD1070 IL-1beta


EOL-1 dbcAMP
8.4
7.8
Dermal fibroblast
9.2
7.7


PMA/ionomycin


IFN gamma


Dendritic cells
7.5
8.0
Dermal fibroblast
9.7
7.5


none


IL-4


Dendritic cells LPS
5.7
4.6
Dermal
10.1
8.5





Fibroblasts rest


Dendritic cells
7.7
6.9
Neutrophils
11.4
5.8


anti-CD40


TNFa + LPS


Monocytes rest
8.5
7.5
Neutrophils rest
3.0
3.0


Monocytes LPS
24.8
25.9
Colon
13.0
9.6


Macrophages rest
8.4
5.6
Lung
16.4
8.4


Macrophages LPS
12.2
5.9
Thymus
10.9
8.8


HUVEC none
8.7
12.8
Kidney
6.3
4.7


HUVEC starved
11.8
11.7










[2258] CNS_neurodegeneration_v1.0 Summary: Ag3647 This panel confirms the expression of this gene at moderate levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.


[2259] General_screening_panel_v1.4 Summary: Ag3647 Expression of the CG88613-01 gene is highest in a gastric cancer cell line (CT=28). Expression of this gene appears to be upregulated in a number of cancer cell lines when compared to normal tissues. Specifically, CG88613-01 gene expression is somewhat higher in breast and ovarian cancers when compared to their respective normal tissues. Thus, therapeutic modulation of the activity of this gene or its protein product, using small molecule drugs, antibodies or protein therapeutics, may be of benefit in the treatment of gastric, breast and ovarian cancer.


[2260] In addition, this gene is expressed at moderate levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. The CG88613-01 gene encodes a protein that is identical to a protein now known in the public domain as inositol 1,4,5-triphosphate 3-kinase C (ref. 1). Inositol 1,4,5-trisphosphate 3-kinase (ITPK) catalyzes the phosphorylation of Ins(1,4,5)P3 to Ins(1,4,5)P4, both of which are modulators of calcium homeostasis. Calcium is one of the most important intracellular messengers in the brain, being essential for neuronal development, synaptic transmission and plasticity, and the regulation of various metabolic pathways (ref. 2). Therefore, this gene may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression. Furthermore, this gene is also expressed in tissues with metabolic or endocrine function, including pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.



REFERENCES

[2261] 1. Dewaste V, Pouillon V, Moreau C, Shears S, Takazawa K, Erneux C. Cloning and expression of a cDNA encoding human inositol 1,4,5-trisphosphate 3-kinase C. Biochem J Dec. 1, 2000;352 Pt 2:343-51


[2262] 2. Mattson M P, Chan S L. Dysregulation of cellular calcium homeostasis in Alzheimer's disease: bad genes and bad habits. J Mol Neurosci October 2001;17(2):205-24


[2263] Panel 4.1D Summary: Ag3647 Results from two experiments using the same probe/primer set are in excellent agreement. Expression of the CG88613-01 gene is highest in keratinocytes treated with the inflammatory cytokines TNF-a and IL-1b(CT=29.5). Therefore, modulation of the expression or activity of this protein through the application of small molecule therapeutics may be useful in the treatment of psoriasis and wound healing.


[2264] This gene is also expressed at moderate levels in small airway epithelial cells, bronchial epithelium, and lung microvascular endothelial cells. Endothelial cells are known to play important roles in inflammatory responses by altering the expression of surface proteins that are involved in activation and recruitment of effector inflammatory cells (ref. 1). Expression in small airway epithelial cells, bronchial epithelium, lung microvascular endothelial cells suggests that the protein encoded by this transcript may be involved in lung disorders including asthma, allergies, chronic obstructive pulmonary disease, and emphysema. This gene is homologoust o PI-3-kinase which is involved in cell survival and receptor signaling of a number of cells of importance in the immune response in health and disease, including lung pathologies. Therefore, Small molecule antagonists of this gene product may lead to amelioration of symptoms associated with asthma, allergies, chronic obstructive pulmonary disease, and emphysema.


[2265] This gene is expressed at low levels in the remainder of the samples on this panel, suggesting that the gene product may play an important role in homeostasis of a number of cell types.



REFERENCES

[2266] 1. Siddiqui R A, English D. Phosphatidylinositol 3′-kinase-mediated calcium mobilization regulates chemotaxis in phosphatidic acid-stimulated human neutrophils. Biochim Biophys Acta Jan. 3, 2000;1483(1):161-73


[2267] 2. Condliffe A M, Cadwallader K A, Walker T R, Rintoul R C, Cowburn A S, Chilvers E R. Phosphoinositide 3-kinase: a critical signalling event in pulmonary cells. Respir Res 2000;1(1):24-9


[2268] DK. CG59993-01 and CG59993-02: Synaptotagmin II


[2269] Expression of gene CG59993-01 and variant CG59993-02 was assessed using the primer-probe set Ag3645, described in Table DKA. Results of the RTQ-PCR runs are shown in Tables DKB, DKC and DKD.
1056TABLE DKAProbe Name Ag3645StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-gaagaagaccctgaacccatac-3′221056746ProbeTET-5′-agctttgagatccccttcgagcagat-3′-TAMRA261093747Reverse5′-tgaccactacctggactttctg-3′221120748


[2270]

1057





TABLE DKB










CNS_neurodegeneration_v1.0











Rel. Exp.

Rel. Exp.



(%) Ag3645,

(%) Ag3645



Run

Run


Tissue Name
211019104
Tissue Name
211019104













AD 1 Hippo
0.4
Control (Path) 3
0.2




Temporal Ctx


AD 2 Hippo
0.2
Control (Path) 4
7.2




Temporal Ctx


AD 3 Hippo
0.0
AD 1 Occipital
8.7




Ctx


AD 4 Hippo
0.1
AD 2 Occipital
0.0




Ctx (Missing)


AD 5 hippo
100.0
AD 3 Occipital
0.6




Ctx


AD 6 Hippo
1.5
AD 4 Occipital
10.7




Ctx


Control 2 Hippo
0.9
AD 5 Occipital
19.2




Ctx


Control 4 Hippo
0.1
AD 6 Occipital
57.8




Ctx


Control (Path) 3
0.0
Control 1 Occipital
0.3


Hippo

Ctx


AD 1 Temporal Ctx
0.8
Control 2 Occipital
81.8




Ctx


AD 2 Temporal Ctx
2.8
Control 3 Occipital
11.0




Ctx


AD 3 Temporal Ctx
0.3
Control 4 Occipital
0.5




Ctx


AD 4 Temporal Ctx
2.6
Control (Path) 1
29.1




Occipital Ctx


AD 5 Inf Temporal
50.0
Control (Path) 2
8.5


Ctx

Occipital Ctx


AD 5 SupTemporal
0.9
Control (Path) 3
0.7


Ctx

Occipital Ctx


AD 6 Inf Temporal
2.8
Control (Path) 4
12.8


Ctx

Occipital Ctx


AD 6 Sup Temporal
8.2
Control 1 Parietal
0.4


Ctx

Ctx


Control 1 Temporal
0.1
Control 2 Parietal
2.3


Ctx

Ctx


Control 2 Temporal
7.2
Control 3 Parietal
28.7


Ctx

Ctx


Control 3 Temporal
1.5
Control (Path) 1
33.2


Ctx

Parietal Ctx


Control 4 Temporal
0.7
Control (Path) 2
21.8


Ctx

Parietal Ctx


Control (Path) 1
4.7
Control (Path) 3
0.5


Temporal Ctx

Parietal Ctx


Control (Path) 2
6.8
Control (Path) 4
68.3


Temporal Ctx

Parietal Ctx










[2271]

1058





TABLE DKC










General_screening_panel_v1.4











Rel. Exp.

Rel. Exp.



(%) Ag3645,

(%) Ag3645,



Run

Run


Tissue Name
218341901
Tissue Name
218341901













Adipose
0.0
Renal ca. TK-10
0.1


Melanoma*
0.1
Bladder
0.1


Hs688(A).T


Melanoma*
0.1
Gastric ca. (liver met.)
0.0


Hs688(B).T

NCI-N87


Melanoma* M14
0.0
Gastric ca. KATO III
0.0


Melanoma*
0.0
Colon ca. SW-948
0.0


LOXIMVI


Melanoma* SK-
0.4
Colon ca. SW480
0.0


MEL-5


Squamous cell
0.1
Colon ca.* (SW480
0.0


carcinoma SCC-4

met) SW620


Testis Pool
1.0
Colon ca. HT29
0.0


Prostate ca.* (bone
0.0
Colon ca. HCT-116
0.0


met) PC-3


Prostate Pool
0.1
Colon ca. CaCo-2
0.6


Placenta
0.0
Colon cancer tissue
0.0


Uterus Pool
0.0
Colon ca. SW1116
0.0


Ovarian ca.
0.2
Colon ca. Colo-205
0.0


OVCAR-3


Ovarian ca. SK-
0.0
Colon ca. SW-48
0.2


OV-3


Ovarian ca.
0.2
Colon Pool
0.2


OVCAR-4


Ovarian ca.
0.1
Small Intestine Pool
0.1


OVCAR-5


Ovarian ca.
0.0
Stomach Pool
0.1


IGROV-1


Ovarian ca.
0.0
Bone Marrow Pool
0.0


OVCAR-8


Ovary
0.7
Fetal Heart
0.1


Breast ca. MCF-7
0.0
Heart Pool
0.0


Breast ca. MDA-
1.4
Lymph Node Pool
1.0


MB-231


Breast ca. BT 549
0.2
Fetal Skeletal Muscle
0.0


Breast ca. T47D
0.1
Skeletal Muscle Pool
0.0


Breast ca. MDA-N
0.0
Spleen Pool
0.1


Breast Pool
0.2
Thymus Pool
0.5


Trachea
0.2
CNS cancer
0.0




(glio/astro) U87-MG


Lung
0.3
CNS cancer
0.0




(glio/astro) U-118-MG


Fetal Lung
0.5
CNS cancer
0.2




(neuro; met) SK-N-AS


Lung ca. NCI-N417
0.5
CNS cancer (astro)
0.0




SF-539


Lung ca. LX-1
0.0
CNS cancer (astro)
0.2




SNB-75


Lung ca. NCI-H146
0.1
CNS cancer (glio)
0.0




SNB-19


Lung ca. SHP-77
0.3
CNS cancer (glio)
0.1




SF-295


Lung ca. A549
0.0
Brain (Amygdala)
5.9




Pool


Lung ca. NCI-H526
0.0
Brain (cerebellum)
100.0


Lung ca. NCI-H23
0.2
Brain (fetal)
0.9


Lung ca. NCI-H460
0.0
Brain (Hippocampus)
2.1




Pool


Lung ca. HOP-62
0.0
Cerebral Cortex Pool
19.3


Lung ca. NCI-H522
0.0
Brain (Substantia
19.5




nigra) Pool


Liver
0.0
Brain (Thalamus) Pool
14.1


Fetal Liver
0.0
Brain (whole)
10.0


Liver ca. HepG2
0.0
Spinal Cord Pool
15.9


Kidney Pool
0.1
Adrenal Gland
0.9


Fetal Kidney
0.6
Pituitary gland Pool
0.0


Renal ca. 786-0
0.0
Salivary Gland
0.0


Renal ca. A498
0.0
Thyroid (female)
0.1


Renal ca. ACHN
0.0
Pancreatic ca.
0.0




CAPAN2


Renal ca. UO-31
0.0
Pancreas Pool
0.8










[2272]

1059





TABLE DKD










Panel 4.1D











Rel.

Rel.



Exp.

Exp.



(%)

(%)



Ag3645,

Ag3645,



Run

Run


Tissue Name
169975206
Tissue Name
169975206













Secondary Th1 act
0.0
HUVEC IL-1beta
0.0


Secondary Th2 act
0.0
HUVEC IFN gamma
0.0


Secondary Tr1 act
0.0
HUVEC TNF alpha +
0.0




IFN gamma


Secondary Th1 rest
0.0
HUVEC TNF alpha +
0.0




IL4


Secondary Th2 rest
0.0
HUVEC IL-11
0.0


Secondary Tr1 rest
0.0
Lung Microvascular
0.0




EC none


Primary Th1 act
0.0
Lung Microvascular
0.0




EC TNFalpha +




IL-1beta


Primary Th2 act
0.0
Microvascular Dermal
0.0




EC none


Primary Tr1 act
0.0
Microvasular Dermal
0.0




EC TNFalpha +




IL-1beta


Primary Th1 rest
0.0
Bronchial epithelium
0.0




TNFalpha + IL1beta


Primary Th2 rest
0.0
Small airway
0.0




epithelium none


Primary Tr1 rest
0.0
Small airway
0.0




epithelium




TNFalpha + IL-beta


CD45RA CD4
0.0
Coronery artery
0.0


lymphocyte act

SMC rest


CD45RO CD4
0.0
Coronery artery
0.0


lymphocyte act

SMC TNFalpha +




IL-1beta


CD8 lymphocyte act
0.0
Astrocytes rest
0.0


Secondary CD8
0.0
Astrocytes
100.0


lymphocyte rest

TNFalpha +




IL-1beta


Secondary CD8
0.0
KU-812 (Basophil)
0.0


lymphocyte act

rest


CD4 lymphocyte
0.0
KU-812 (Basophil)
0.0


none

PMA/ionomycin


2ry Th1/Th2/
0.0
CCD1106
0.0


Tr1_anti-

(Keratinocytes)


CD95 CH11

none


LAK cells rest
0.0
CCD1106
0.0




(Keratinocytes)




TNFalpha + IL-1beta


LAK cells IL-2
0.0
Liver cirrhosis
0.0


LAK cells IL-2 +
0.0
NCI-H292 none
15.0


IL-12


LAK cells IL-2 +
8.3
NCI-H292 IL-4
0.0


IFN gamma


LAK cells IL-2 +
0.0
NCI-H292 IL-9
22.5


IL-18


LAK cells
0.0
NCI-H292 IL-13
0.0


PMA/ionomycin


NK Cells IL-2 rest
0.0
NCI-H292 IFN gamma
0.0


Two Way MLR
0.0
HPAEC none
0.0


3 day


Two Way MLR
0.0
HPAEC TNF alpha +
0.0


5 day

IL-1beta


Two Way MLR
0.0
Lung fibroblast none
0.0


7 day


PBMC rest
0.0
Lung fibroblast
4.3




TNF alpha +




IL-1beta


PBMC PWM
0.0
Lung fibroblast IL-4
0.0


PBMC PHA-L
12.9
Lung fibroblast IL-9
0.0


Ramos (B cell) none
0.0
Lung fibroblast IL-13
36.9


Ramos (B cell)
0.0
Lung fibroblast IFN
0.0


ionomycin

gamma


B lymphocytes
0.0
Dermal fibroblast
0.0


PMW

CCD1070 rest


B lymphocytes
0.0
Dermal fibroblast
0.0


CD40L and IL-4

CCD1070 TNF alpha


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0




CCD1070 IL-1beta


EOL-1 dbcAMP
48.6
Dermal fibroblast IFN
0.0


PMA/ionomycin

gamma


Dendritic cells none
0.0
Dermal fibroblast IL-4
0.0


Dendritic cells LPS
0.0
Dermal Fibroblasts
0.0




rest


Dendritic cells anti-
20.9
Neutrophils TNFa +
0.0


CD40

LPS


Monocytes rest
0.0
Neutrophils rest
0.0


Monocytes LPS
0.0
Colon
25.7


Macrophages rest
0.0
Lung
28.7


Macrophages LPS
0.0
Thymus
43.2


HUVEC none
0.0
Kidney
25.9


HUVEC starved
0.0










[2273] CNS_nturodegeneration_v1.0 Summary: Ag3645 While no association between the expression of the CG59993-01 gene and the presence of Alzheimer's disease is detected in this panel, these results confirm the expression of this gene in areas that degenerate in Alzheimer's disease, including the cortex and hippocampus. Synaptotagmin expression is altered in the brain of Alzheimer's patients, possibly explaining impaired synaptogenesis and/or synaptosomal loss secondary to neuronal loss observed in the neurodegenerative disorder. It may also represent, reflect or account for the impaired neuronal transmission in Alzheimer's disease (AD), caused by deterioration of the exocytic machinery. Since the this gene is a homolog of synaptotagmin, agents that potentiate the expression or function of the protein encoded by the this gene may be useful in the treatment of Alzheimer's disease.


[2274] General_screening_panel_v1.4 Summary: Ag3645 The CG59993-01 gene is a homolog of synaptotagmin, and shows high to moderate expression across all brain regions with highest expression in the cerebellum (CT=26.4) Synaptotagmin is a presynaptic protein involved in synaptic vesicle release, making this an ideal drug target for diseases such as epilepsy, in which reduction of neurotransmission is beneficial. Selective inhibition of this gene or its protein product may therefore be useful in the treatment of seizure disorders. Furthermore, selective inhibition of neural transmission through antagonism of the protein encoded by this gene may show therapeutic benefit in psychiatric diseases where it is believed that inappropriate neural connections have been established, such as schizophrenia and bipolar disorder. In addition, antibodies against synaptotagmin may cause Lambert-Eaton myasthenic syndrome. Therefore, peptide fragments of the protein encoded by this gene may serve to block the action of these antibodies and treat Lambert-Eaton myasthenic syndrome.


[2275] Panel 4.1D Summary: Ag3645 Expression of the CG59993-01 gene is restricted to a sample derived from astrocytes treated with TNF-alpha and IL-1 beta (CT=33.9). This expression in samples related to the central nervous system is consistent with results of the previous panels and suggests that modulation of this protein could be beneficial in the treatment of CNS disease-associated inflammation or neurodegeneration, including mutliple sclerosis.


[2276] DL. CG59991-01: Ooplasm Specific Protein


[2277] Expression of gene CG59991-01 was assessed using the primer-probe set Ag3644, described in Table DLA. Results of the RTQ-PCR runs are shown in Tables DLB and DLC.
1060TABLE DLAProbe Name Ag3644StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-gggagtaatgcctctcagtga-3′212294749ProbeTET-5′-cttgagagtctcccagtgcgccct-3′-TAMRA242318750Reverse5′-atgccacagtcctccagtatc-3′212351751


[2278]

1061





TABLE DLB










General_screening_panel_v1.4











Rel.

Rel.



Exp.

Exp.



(%)

(%)



Ag3644,

Ag3644,



Run

Run


Tissue Name
218306573
Tissue Name
218306573













Adipose
0.0
Renal ca. TK-10
0.0


Melanoma*
0.0
Bladder
0.0


Hs688(A).T


Melanoma*
0.0
Gastric ca. (liver met.)
0.0


Hs688(B).T

NCI-N87


Melanoma* M14
0.0
Gastric ca. KATO III
0.1


Melanoma*
0.0
Colon ca. SW-948
0.0


LOXIMVI


Melanoma* SK-
0.0
Colon ca. SW480
0.0


MEL-5


Squamous cell
0.0
Colon ca.* (SW480
0.0


carcinoma SCC-4

met) SW620


Testis Pool
0.5
Colon ca. HT29
0.0


Prostate ca.* (bone
0.0
Colon ca. HCT-116
0.1


met) PC-3


Prostate Pool
0.0
Colon ca. CaCo-2
0.0


Placenta
0.0
Colon cancer tissue
0.0


Uterus Pool
0.0
Colon ca. SW1116
0.0


Ovarian ca.
0.0
Colon ca. Colo-205
0.0


OVCAR-3


Ovarian ca.
0.0
Colon ca. SW-48
0.0


SK-OV-3


Ovarian ca.
0.6
Colon Pool
0.0


OVCAR-4


Ovarian ca.
0.0
Small Intestine Pool
0.0


OVCAR-5


Ovarian ca.
0.0
Stomach Pool
0.0


IGROV-1


Ovarian ca.
0.0
Bone Marrow Pool
0.0


OVCAR-8


Ovary
0.0
Fetal Heart
0.0


Breast ca. MCF-7
0.0
Heart Pool
0.0


Breast ca. MDA-
0.0
Lymph Node Pool
0.0


MB-231


Breast ca. BT 549
0.0
Fetal Skeletal Muscle
0.0


Breast ca. T47D
0.0
Skeletal Muscle Pool
0.0


Breast ca. MDA-N
0.0
Spleen Pool
0.0


Breast Pool
0.0
Thymus Pool
0.0


Trachea
0.0
CNS cancer
0.0




(glio/astro)




U87-MG


Lung
0.0
CNS cancer
0.0




(glio/astro)




U-118-MG


Fetal Lung
0.0
CNS cancer
0.0




(neuro; met)




SK-N-AS


Lung ca. NCI-N417
0.0
CNS cancer
0.0




(astro)




SF-539


Lung ca. LX-1
0.0
CNS cancer (astro)
0.0




SNB-75


Lung ca. NCI-H146
0.0
CNS cancer (glio)
0.0




SNB-19


Lung ca. SHP-77
100.0
CNS cancer (glio)
0.3




SF-295


Lung ca. A549
0.0
Brain (Amygdala)
0.0




Pool


Lung ca. NCI-H526
0.0
Brain (cerebellum)
0.0


Lung ca. NCI-H23
0.0
Brain (fetal)
0.0


Lung ca. NCI-H460
0.0
Brain (Hippocampus)
0.0




Pool


Lung ca. HOP-62
0.0
Cerebral Cortex Pool
0.0


Lung ca. NCI-H522
0.0
Brain
0.0




(Substantia nigra)




Pool


Liver
0.0
Brain (Thalamus) Pool
0.0


Fetal Liver
0.0
Brain (whole)
0.0


Liver ca. HepG2
0.0
Spinal Cord Pool
0.0


Kidney Pool
0.0
Adrenal Gland
0.0


Fetal Kidney
0.0
Pituitary gland Pool
0.0


Renal ca. 786-0
0.0
Salivary Gland
0.0


Renal ca. A498
0.0
Thyroid (female)
0.1


Renal ca. ACHN
0.0
Pancreatic ca.
0.0




CAPAN2


Renal ca. UO-31
0.0
Pancreas Pool
0.1










[2279]

1062





TABLE DLC










Panel 4.1D











Rel.

Rel.



Exp.

Exp.



(%)

(%)



Ag3644,

Ag3644,



Run

Run


Tissue Name
169975188
Tissue Name
169975188













Secondary Th1 act
0.0
HUVEC IL-beta
0.0


Secondary Th2 act
0.0
HUVEC IFN gamma
0.0


Secondary Tr1 act
0.0
HUVEC TNF alpha +
0.0




IFN gamma


Secondary Th1 rest
0.0
HUVEC TNF alpha +
0.0




IL4


Secondary Th2 rest
0.0
HUVEC IL-11
0.0


Secondary Tr1 rest
0.0
Lung Microvascular
0.0




EC none


Primary Th1 act
0.0
Lung Microvascular
0.0




EC TNFalpha +




IL-1beta


Primary Th2 act
0.0
Microvascular Dermal
0.0




EC none


Primary Tr1 act
0.0
Microvasular Dermal
0.0




EC TNFalpha +




IL-1beta


Primary Tr1 act
0.0
Microvascular Dermal
0.0




EC TNFalpha +




IL-1beta


Primary Th1 rest
0.0
Bronchial epithelium
0.0




TNFalpha + IL1beta


Primary Th2 rest
0.0
Small airway
0.0




epithelium none


Primary Tr1 rest
0.0
Small airway
0.0




epithelium




TNFalpha + IL-beta


CD45RA CD4
0.0
Coronery artery
0.0


lymphocyte act

SMC rest


CD45RO CD4
0.0
Coronery artery
0.0


lymphocyte act

SMC TNFalpha +




IL-1beta


CD8 lymphocyte act
0.0
Astrocytes rest
0.0


Secondary CD8
0.0
Astrocytes
0.0


lymphocyte rest

TNFalpha +




IL-1beta


Secondary CD8
0.0
KU-812 (Basophil)
48.3


lynphocyte act

rest


CD4 lymphocyte
0.0
KU-812 (Basophil)
100.0


none

PMA/ionomycin


2ry Th1/Th2/
0.0
CCD1106
0.0


Tr1_anti-

(Keratinocytes)


CD95 CH11

none


LAK cells rest
0.0
CCD1106
0.0




(Keratinocytes)




TNFalpha + IL-1beta


LAK cells IL-2
0.0
Liver cirrhosis
0.0


LAK cells IL-2 +
0.0
NCI-H292 none
0.0


IL-12


LAK cells IL-2 +
0.0
NCI-H292 IL-4
0.0


IFN gamma


LAK cells IL-2 +
0.0
NCI-H292 IL-9
0.0


IL-18


LAK cells
0.0
NCI-H292 IL-13
0.0


PMA/ionomycin


NK Cells IL-2 rest
0.0
NCI-H292 IFN gamma
0.0


Two Way MLR
0.0
HPAEC none
0.0


3 day


Two Way MLR
0.0
HPAEC TNF alpha +
0.0


5 day

IL-1beta


Two Way MLR
0.0
Lung fibroblast none
0.0


7 day


PBMC rest
0.0
Lung fibroblast
0.0




TNF alpha +




IL-1beta


PBMC PWM
0.0
Lung fibroblast IL-4
0.0


PBMC PHA-L
0.0
Lung fibroblast IL-9
0.0


Ramos (B cell) none
0.0
Lung fibroblast IL-13
0.0


Ramos (B cell)
0.0
Lung fibroblast IFN
0.0


ionomycin

gamma


B lymphocytes
0.0
Dermal fibroblast
0.0


PMW

CCD1070 rest


B lymphocytes
0.0
Dermal fibroblast
0.0


CD40L and IL-4

CCD1070 TNF alpha


EOL-1 dbcAMP
0.0
Dermal fibroblast
0.0




CCD1070 IL-1beta


EOL-1 dbcAMP
0.0
Dermal fibroblast IFN
0.0


PMA/ionomycin

gamma


Dendritic cells none
0.0
Dermal fibroblast IL-4
0.0


Dendritic cells LPS
0.0
Dermal Fibroblasts
0.0




rest


Dendritic cells anti-
0.0
Neutrophils TNFa +
0.0


CD40

LPS


Monocytes rest
0.0
Neutrophils rest
0.0


Monocytes LPS
0.0
Colon
0.0


Macrophages rest
0.0
Lung
0.0


Macrophages LPS
0.0
Thymus
0.0


HUVEC none
0.0
Kidney
0.0


HUVEC starved
0.0










[2280] CNS_neurodegeneration1.0 Summary: Ag3644 Expression of the CG59991-01 gene is low/undetectable in all samples on this panel (CTs>35). (Data not shown).


[2281] General_screening_panel_v1.4 Summary: Ag3644 Expression of the CG59991-01 gene is restricted to a sample derived from a lung cancer cell line (CT=27.2). Thus, expression of this gene could be used to differentiate between this sample and other samples on this panel and as a marker to detect the presence of lung cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of lung cancer.


[2282] Panel 4.1D Summary: Ag3644 Expression of the CG59991-01 gene is restricted to samples derived from the basophil cell line KU-812 (CTs=32). Thus, expression of this gene could be used as a marker of this cell type. Basophils release histamines and other biological modifiers in repose to allergens and play an important role in the pathology of asthma and hypersensitivity reactions. Therefore, the specific pattern of expression of this gene suggests that therapeutic modulation of the expression or function of the protein encoded by this gene may block or inhibit inflammation or tissue damage due to basophil activation in response to asthma, allergies, hypersensitivity reactions, psoriasis, and viral infections.


[2283] DM. CG59987-01 and CG59987-02: Rhophilin


[2284] Expression of gene CG59987-01 and full length clone CG59987-02 was assessed using the primer-probe set Ag3643, described in Table DMA. Results of the RTQ-PCR runs are shown in Tables DMB and DMC. Please note that CG59987-02 represents a full-length physical clone of the CG59987-01 gene, validating the prediction of the gene sequence.


[2285] Table DMA. Probe Name Ag3643
1063TABLE DMAProbe Name Ag3643StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′-tactttcggaagggctgtaatc-3′22103752ProbeTET-5′-cttgcacaaaccggccggagtaaatt-3′-TAMRA26127753Reverse5′-tgattcaaagcagctctttgat-3′22158754


[2286]

1064





TABLE DMB










General_screening_panel_v1.4











Rel.

Rel.



Exp.

Exp.



(%)

(%)



Ag3643,

Ag3643,



Run

Run


Tissue Name
218306426
Tissue Name
218306426













Adipose
1.4
Renal ca. TK-10
17.2


Melanoma*
0.5
Bladder
9.1


Hs688(A).T


Melanoma*
0.6
Gastric ca. (liver met.)
46.7


Hs688(B).T

NCI-N87


Melanoma* M14
6.3
Gastric ca. KATO III
39.2


Melanoma*
1.7
Colon ca. SW-948
16.6


LOXIMVI


Melanoma* SK-
8.7
Colon ca. SW480
7.0


MEL-5


Squamous cell
5.4
Colon ca.* (SW480
0.4


carcinoma SCC-4

met) SW620


Testis Pool
0.5
Colon ca. HT29
24.8


Prostate ca.* (bone
7.7
Colon ca. HCT-116
26.8


met) PC-3


Prostate Pool
6.6
Colon ca. CaCo-2
34.2


Placenta
3.3
Colon cancer tissue
13.0


Uterus Pool
0.4
Colon ca. SW1116
4.5


Ovarian ca.
44.1
Colon ca. Colo-205
5.5


OVCAR-3


Ovarian ca.
36.9
Colon ca. SW-48
6.5


SK-OV-3


Ovarian ca.
58.6
Colon Pool
0.9


OVCAR-4


Ovarian ca.
50.7
Small Intestine Pool
1.9


OVCAR-5


Ovarian ca.
20.3
Stomach Pool
2.3


IGROV-1


Ovarian ca.
7.9
Bone Marrow Pool
0.3


OVCAR-8


Ovary
1.6
Fetal Heart
0.7


Breast ca. MCF-7
17.4
Heart Pool
0.4


Breast ca. MDA-
13.7
Lymph Node Pool
1.0


MB-231


Breast ca. BT 549
8.2
Fetal Skeletal Muscle
0.1


Breast ca. T47D
100.0
Skeletal Muscle Pool
0.2


Breast ca. MDA-N
4.7
Spleen Pool
0.2


Breast Pool
1.9
Thymus Pool
1.5


Trachea
8.4
CNS cancer
1.0




(glio/astro)




U87-MG


Lung
0.3
CNS cancer
1.3




(glio/astro)




U-118-MG


Fetal Lung
6.9
CNS cancer
5.2




(neuro; met)




SK-N-AS


Lung ca. NCI-N417
0.9
CNS cancer
2.5




(astro)




SF-539


Lung ca. LX-1
0.2
CNS cancer (astro)
6.0




SNB-75


Lung ca. NCI-H146
1.9
CNS cancer (glio)
21.6




SNB-19


Lung ca. SHP-77
0.0
CNS cancer (glio)
14.7




SF-295


Lung ca. A549
54.3
Brain (Amygdala)
1.0




Pool


Lung ca. NCI-H526
3.7
Brain (cerebellum)
5.2


Lung ca. NCI-H23
3.2
Brain (fetal)
0.7


Lung ca. NCI-H460
1.2
Brain (Hippocampus)
1.9




Pool


Lung ca. HOP-62
6.5
Cerebral Cortex Pool
2.3


Lung ca. NCI-H522
3.7
Brain
2.1




(Substantia nigra)




Pool


Liver
1.5
Brain (Thalamus) Pool
2.7


Fetal Liver
5.6
Brain (whole)
3.5


Liver ca. HepG2
7.0
Spinal Cord Pool
3.6


Kidney Pool
1.4
Adrenal Gland
0.2


Fetal Kidney
3.4
Pituitary gland Pool
1.3


Renal ca. 786-0
12.2
Salivary Gland
6.7


Renal ca. A498
8.8
Thyroid (female)
1.2


Renal ca. ACHN
9.1
Pancreatic ca.
21.3




CAPAN2


Renal ca. UO-31
9.9
Pancreas Pool
12.2










[2287]

1065





TABLE CMD










Panel 4.1D











Rel.

Rel.



Exp.

Exp.



(%)

(%)



Ag3643,

Ag3643,



Run

Run


Tissue Name
169975145
Tissue Name
169975145













Secondary Th1 act
3.8
HUVEC IL-1beta
6.9


Secondary Th2 act
1.1
HUVEC IFN gamma
4.4


Secondary Tr1 act
0.9
HUVEC TNF alpha +
2.6




IFN gamma


Secondary Th1 rest
0.5
HUVEC TNF alpha +
4.0




IL4


Secondary Th2 rest
0.9
HUVEC IL-11
2.5


Secondary Tr1 rest
0.6
Lung Microvascular
4.3




EC none


Primary Th1 act
1.8
Lung Microvascular
1.5




EC TNFalpha +




IL-1beta


Primary Th2 act
5.0
Microvascular Dermal
6.7




EC none


Primary Tr1 act
3.4
Microvascular Dermal
7.7




EC TNFalpha +




IL-1beta


Primary Th1 rest
1.0
Bronchial epithelium
17.7




TNFalpha + IL1beta


Primary Th2 rest
0.8
Small airway
13.7




epithelium none


Primary Tr1 rest
0.9
Small airway
23.3




epithelium




TNFalpha + IL-beta


CD45RA CD4
3.5
Coronery artery
6.7


lymphocyte act

SMC rest


CD45RO CD4
3.0
Coronery artery
4.3


lymphocyte act

SMC TNFalpha +




IL-1beta


CD8 lymphocyte act
6.2
Astrocytes rest
35.4


Secondary CD8
3.4
Astrocytes
24.3


lymphocyte rest

TNFalpha +




IL-1beta


Secondary CD8
0.0
KU-812 (Basophil)
0.5


lynphocyte act

rest


CD4 lymphocyte
0.0
KU-812 (Basophil)
2.3


none

PMA/ionomycin


2ry Th1/Th2/
0.0
CCD1106
39.8


Tr1_anti-

(Keratinocytes)


CD95 CH11

none


LAK cells rest
0.7
CCD1106
32.5




(Keratinocytes)




TNFalpha + IL-1beta


LAK cells IL-2
0.4
Liver cirrhosis
41.2


LAK cells IL-2 +
1.3
NCI-H292 none
49.3


IL-12


LAK cells IL-2 +
2.2
NCI-H292 IL-4
45.1


IFN gamma


LAK cells IL-2 +
2.0
NCI-H292 IL-9
100.0


IL-18


LAK cells
1.7
NCI-H292 IL-13
51.8


PMA/ionomycin


NK Cells IL-2 rest
0.5
NCI-H292 IFN gamma
53.6


Two Way MLR
0.4
HPAEC none
8.0


3 day


Two Way MLR
0.8
HPAEC TNF alpha +
6.1


5 day

IL-1beta


Two Way MLR
1.5
Long fibroblast none
13.3


7 day


PBMC rest
0.6
Lung fibroblast
7.1




TNF alpha +




IL-1beta


PBMC PWM
4.3
Lung fibroblast IL-4
3.6


PBMC PHA-L
3.6
Lung fibroblast IL-9
8.5


Ramos (B cell) none
14.8
Lung fibroblast IL-13
3.3


Ramos (B cell)
15.7
Lung fibroblast IFN
10.5


ionomycin

gamma


B lymphocytes
6.3
Dermal fibroblast
5.1


PMW

CCD1070 rest


B lymphocytes
6.5
Dermal fibroblast
5.6


CD40L and IL-4

CCD1070 TNF alpha


EOL-1 dbcAMP
0.0
Dermal fibroblast
7.7




CCD1070 IL-1beta


EOL-1 dbcAMP
0.0
Dermal fibroblast IFN
5.5


PMA/ionomycin

gamma


Dendritic cells none
0.5
Dermal fibroblast IL-4
3.7


Dendritic cells LPS
0.0
Dermal Fibroblasts
1.5




rest


Dendritic cells anti-
41.8
Neutrophils TNFa +
0.0


CD40

LPS


Monocytes rest
100.0
Neutrophils rest
0.0


Monocytes LPS
77.4
Colon
34.6


Macrophages rest
62.4
Lung
4.3


Macrophages LPS
15.9
Thymus
9.9


HUVEC none
20.0
Kidney
51.4


HUVEC starved
30.6










[2288] CNS_neurodegeneration_v1.0 Summary: Ag3643 Results from one experiment with the CG59987-01 gene are not included. The amp plot indicates that there were experimental difficulties with this run.


[2289] General_screening_panel_v1.4 Summary: Ag3643 Expression of the CG59987-01 gene is highest in a breast cancer cell line (CT=25.3). In addition, significant levels of expression are seen in clusters of cell lines derived from brain, gastric, colon, lung, and ovarian cancers. In addition, expression overall appears to be higher in samples derived from cancer cell lines than in normal tissues. Thus, expression of this gene could be used as a marker to detect the presence of cancer. This gene encodes a homolog of rhophilin, a rho GTPase that is involved in a signaling pathway that regulates cell adhesion, among other functions. Therefore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of these cancers.


[2290] Among tissues with metabolic function, this gene is expressed at moderate to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, skeletal muscle, and adult and fetal heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.


[2291] This gene is also expressed at moderate to low levels in the CNS and may be a small molecule target for the treatment of neurologic diseases.


[2292] Panel 4.1D Summary: Ag3643 Expression of the CG59987-01 gene is highest in NCI-H292 cells stimulated by IL-9(CT=29.2). The gene is also expressed in a cluster of treated and untreated NCI-H292 mucoepidermoid cell line samples. The transcript is also expressed at lower but still significant levels in both small airway and bronchial epithelium treated with IL-1 beta and TNF-alpha. In comparison, expression in the normal lung is relatively low. The expression of the transcript in activated normal epithelium as well as a cell line that is often used as a model for airway epithelium (NCI-H292 cells) suggests that this transcript may be important in the proliferation or activation of airway epithelium. Therefore, therapuetics designed with the protein encoded by this transcript could be important in the treatment of diseases which include lung airway inflammation such as asthma and COPD.


[2293] DN. CG59971-01 and CG59971-02: Leucine Rich Repeat Protein


[2294] Expression of gene CG59971-01 and variant CG59971-02 was assessed using the primer-probe set Ag3639, described in Table DNA. Results of the RTQ-PCR runs are shown in Tables DNB and DNC.
1066TABLE DNAProbe Name Ag3639StartSEQ IDPrimersSequencesLengthPositionNO:Forward5′ttctgaacttcagctacaat-3′22510755ProbeTET-5′-cttagacagctccctgcgcctcttgt-3′-TAMRA26543756Reverse5′-acttgattgtggcttaggttca-3′22584757


[2295]

1067





TABLE DNB










General_screening_panel_v1.4











Rel.

Rel.



Exp.

Exp.



(%)

(%)



Ag3639,

Ag3639,



Run

Run


Tissue Name
218234144
Tissue Name
218234144













Adipose
3.2
Renal ca. TK-10
24.0


Melanoma*
17.9
Bladder
11.8


Hs688(A).T


Melanoma*
12.6
Gastric ca. (liver met.)
35.6


Hs688(B).T

NCI-N87


Melanoma* M14
64.6
Gastric ca. KATO III
35.8


Melanoma*
15.5
Colon ca. SW-948
8.0


LOXIMVI


Melanoma* SK-
25.2
Colon ca. SW480
55.5


MEL-5


Squamous cell
10.5
Colon ca.* (SW480
32.8


carcinoma SCC-4

met) SW620


Testis Pool
8.9
Colon ca. HT29
13.7


Prostate ca.* (bone
19.3
Colon ca. HCT-116
34.9


met) PC-3


Prostate Pool
3.2
Colon ca. CaCo-2
15.4


Placenta
16.3
Colon cancer tissue
14.3


Uterus Pool
1.0
Colon ca. SW1116
7.9


Ovarian ca.
19.9
Colon ca. Colo-205
13.3


OVCAR-3


Ovarian ca.
30.1
Colon ca. SW-48
8.8


SK-OV-3


Ovarian ca.
14.8
Colon Pool
8.2


OVCAR-4


Ovarian ca.
60.7
Small Intestine Pool
7.7


OVCAR-5


Ovarian ca.
15.1
Stomach Pool
3.9


IGROV-1


Ovarian ca.
9.5
Bone Marrow Pool
2.7


OVCAR-8


Ovary
12.6
Fetal Heart
7.2


Breast ca. MCF-7
54.0
Heart Pool
3.7


Breast ca. MDA-
31.2
Lymph Node Pool
10.4


MB-231


Breast ca. BT 549
27.2
Fetal Skeletal Muscle
4.0


Breast ca. T47D
100.0
Skeletal Muscle Pool
3.6


Breast ca. MDA-N
20.4
Spleen Pool
8.4


Breast Pool
8.9
Thymus Pool
15.3


Trachea
10.3
CNS cancer
37.9




(glio/astro)




U87-MG


Lung
1.1
CNS cancer
26.2




(glio/astro)




U-118-MG


Fetal Lung
21.9
CNS cancer
22.4




(neuro; met)




SK-N-AS


Lung ca. NCI-N417
4.5
CNS cancer
15.7




(astro)




SF-539


Lung ca. LX-1
32.8
CNS cancer (astro)
46.7




SNB-75


Lung ca. NCI-H146
7.7
CNS cancer (glio)
12.2




SNB-19


Lung ca. SHP-77
33.2
CNS cancer (glio)
31.4




SF-295


Lung ca. A549
30.83
Brain (Amygdala)
7.9




Pool


Lung ca. NCI-H526
8.7
Brain (cerebellum)
27.4


Lung ca. NCI-H23
23.2
Brain (fetal)
24.3


Lung ca. NCI-H460
18.0
Brain (Hippocampus)
6.8




Pool


Lung ca. HOP-62
9.2
Cerebral Cortex Pool
8.0


Lung ca. NCI-H522
22.5
Brain
8.3




(Substantia nigra)




Pool


Liver
0.8
Brain (Thalamus) Pool
10.7


Fetal Liver
8.8
Brain (whole)
13.8


Liver ca. HepG2
19.3
Spinal Cord Pool
7.6


Kidney Pool
12.9
Adrenal Gland
14.1


Fetal Kidney
8.4
Pituitary gland Pool
6.6


Renal ca. 786-0
20.0
Salivary Gland
3.0


Renal ca. A498
5.2
Thyroid (female)
4.9


Renal ca. ACHN
34.4
Pancreatic ca.
20.9




CAPAN2


Renal ca. UO-31
15.5
Pancreas Pool
10.7










[2296]

1068





TABLE DNC










Panel 4.1D











Rel.

Rel.



Exp.

Exp.



(%)

(%)



Ag3639,

Ag3639,



Run

Run


Tissue Name
169975065
Tissue Name
169975065













Secondary Th1 act
51.8
HUVEC IL-beta
27.0


Secondary Th2 act
68.8
HUVEC IFN gamma
31.2


Secondary Tr1 act
74.7
HUVEC TNF alpha +
28.9




IFN gamma


Secondary Th1 rest
26.4
HUVEC TNF alpha +
26.4




IL4


Secondary Th2 rest
41.5
HUVEC IL-11
22.4


Secondary Tr1 rest
24.1
Lung Microvascular
55.5




EC none


Primary Th1 act
50.3
Lung Microvascular
36.1




EC TNFalpha +




IL-1beta


Primary Th2 act
75.8
Microvascular Dermal
23.5




EC none


Primary Tr1 act
66.4
Microvascular Dermal
33.0




EC TNFalpha +




IL-1beta


Primary Th1 rest
19.8
Bronchial epithelium
22.8




TNFalpha + IL1beta


Primary Th2 rest
33.9
Small airway
23.2




epithelium none


Primary Tr1 rest
64.2
Small airway
37.1




epithelium




TNFalpha + IL-beta


CD45RA CD4
35.4
Coronery artery
21.2


lymphocyte act

SMC rest


CD45RO CD4
59.5
Coronery artery
13.4


lymphocyte act

SMC TNFalpha +




IL-1beta


CD8 lymphocyte act
64.6
Astrocytes rest
23.3


Secondary CD8
36.1
Astrocytes
25.2


lymphocyte rest

TNFalpha +




IL-1beta


Secondary CD8
45.1
KU-812 (Basophil)
22.4


lynphocyte act

rest


CD4 lymphocyte
20.0
KU-812 (Basophil)
32.8


none

PMA/ionomycin


2ry Th1/Th2/
44.1
CCD1106
61.6


Tr1_anti-

(Keratinocytes)


CD95 CH11

none


LAK cells rest
53.2
CCD1106
49.0




(Keratinocytes)




TNFalpha + IL-1beta


LAK cells IL-2
57.4
Liver cirrhosis
8.1


LAK cells IL-2 +
54.0
NCI-H292 none
46.7


IL-12


LAK cells IL-2 +
59.0
NCI-H292 IL-4
45.1


IFN gamma


LAK cells IL-2 +
61.6
NCI-H292 IL-9
58.6


IL-18


LAK cells
39.0
NCI-H292 IL-13
35.6


PMA/ionomycin


NK Cells IL-2 rest
60.7
NCI-H292 IFN gamma
28.9


Two Way MLR
55.1
HPAEC none
18.3


3 day


Two Way MLR
36.6
HPAEC TNF alpha +
44.8


5 day

IL-1beta


Two Way MLR
36.6
Lung fibroblast none
28.3


7 day


PBMC rest
22.2
Lung fibroblast
20.2




TNF alpha +




IL-1beta


PBMC PWM
62.4
Lung fibroblast IL-4
29.1


PBMC PHA-L
42.9
Lung fibroblast IL-9
50.7


Ramos (B cell) none
43.5
Lung fibroblast IL-13
40.3


Ramos (B cell)
46.3
Lung fibroblast IFN
37.4


ionomycin

gamma


B lymphocytes
40.9
Dermal fibroblast
60.3


PMW

CCD1070 rest


B lymphocytes
78.5
Dermal fibroblast
92.7


CD40L and IL-4

CCD1070 TNF alpha


EOL-1 dbcAMP
34.2
Dermal fibroblast
22.7




CCD1070 IL-1beta


EOL-1 dbcAMP
62.0
Dermal fibroblast IFN
24.0


PMA/ionomycin

gamma


Dendritic cells none
65.1
Dermal fibroblast IL-4
35.6


Dendritic cells LPS
25.3
Dermal Fibroblasts
21.8




rest


Dendritic cells anti-
41.8
Neutrophils TNFa +
1.7


CD40

LPS


Monocytes rest
100.0
Neutrophils rest
18.3


Monocytes LPS
77.4
Colon
11.2


Macrophages rest
62.4
Lung
17.7


Macrophages LPS
15.9
Thymus
81.8


HUVEC none
20.0
Kidney
18.6


HUVEC starved
30.6










[2297] CNS_neurodegeneration_v1.0 Summary: Ag3639 Results from one experiment with the CG59971-01 gene are not included. The amp plot indicates that there were experimental difficulties with this run.


[2298] General_screening_panel_v1.4 Summary: Ag3639 Expression of the CG59971-02 gene is ubiquitous in this panel, with highest expression in a breast cancer cell line (CT=26.6). Overall, expression of this gene appears to be higher in samples derived from cancer cell lines than in normal tissues. This widespread expression suggests that this gene product is involved in cell growth and prolideration. Thus, expression of this gene could be used as a marker to detect the presence of cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of cancer.


[2299] In addition, this gene is expressed at much higher levels in fetal lung and liver (CTs=29-30) when compared to expression in the adult counterpart (CTs=33). Thus, expression of this gene may be used to differentiate between the fetal and adult sources of these tissue.


[2300] Among tissues with metabolic function, this gene is expressed at moderate to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.


[2301] This gene is also highly expressed in the brain, with highest expression in the cerebellum (CT=28.5), with moderate expression in other CNS regions as well including, amygdala, hippocampus, cerebral cortex, substantia nigra and thalamus. This gene encodes a leucine-rich repeat protein. Leucine rich repeats (LRR) mediate reversible protein-protein interactions and have diverse cellular functions, including cellular adhesion and signaling. Several of these proteins, such as connectin, slit, chaoptin, and Toll have pivotal roles in neuronal development in Drosophila and may play significant but distinct roles in neural development and in the adult nervous system of humans (Ref. 1). In Drosophilia, the LRR region of axon guidance proteins has been shown to be critical for their function (especially in axon this gene shows high expression in the brain, it is an excellent candidate neuronal guidance protein for axons, dendrites and/or growth cones in general. Therefore, therapeutic modulation of the levels of this protein, or possible signaling via this protein, may be of utility in enhancing/directing compensatory synaptogenesis and fiber growth in the CNS in response to neuronal death (stroke, head trauma), axon lesion (spinal cord injury), or neurodegeneration (Alzheimer's, Parkinson's, Huntington's, vascular dementia or any neurodegenerative disease).



REFERENCES

[2302] 1. Battye R., Stevens A., Perry R. L., Jacobs J. R. (2001) Repellent signaling by Slit requires the leucine-rich repeats. J. Neurosci. 21: 4290-4298.


[2303] Panel 4.1D Summary: Ag3639 The CG59971-01 gene is expressed at high to moderate levels in a wide range of cell types of significance in the immune response in health and disease. Highest expression of the gene is seen in resting monocytes (CT=28.6). Significant levels of expression are also seen in members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.4 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.



Example D


Identification of Single Nucleotide Polymorphisms in NOVX Nucleic Acid Sequences

[2304] Variant sequences are also included in this application. A variant sequence can include a single nucleotide polymorphism (SNP). A SNP can, in some instances, be referred to as a “cSNP” to denote that the nucleotide sequence containing the SNP originates as a cDNA. A SNP can arise in several ways. For example, a SNP may be due to a substitution of one nucleotide for another at the polymorphic site. Such a substitution can be either a transition or a transversion. A SNP can also arise from a deletion of a nucleotide or an insertion of a nucleotide, relative to a reference allele. In this case, the polymorphic site is a site at which one allele bears a gap with respect to a particular nucleotide in another allele. SNPs occurring within genes may result in an alteration of the amino acid encoded by the gene at the position of the SNP. Intragenic SNPs may also be silent, when a codon including a SNP encodes the same amino acid as a result of the redundancy of the genetic code. SNPs occurring outside the region of a gene, or in an intron within a gene, do not result in changes in any amino acid sequence of a protein but may result in altered regulation of the expression pattern. Examples include alteration in temporal expression, physiological response regulation, cell type expression regulation, intensity of expression, and stability of transcribed message.


[2305] SeqCalling assemblies produced by the exon linking process were selected and extended using the following criteria. Genomic clones having regions with 98% identity to all or part of the initial or extended sequence were identified by BLASTN searches using the relevant sequence to query human genomic databases. The genomic clones that resulted were selected for further analysis because this identity indicates that these clones contain the genomic locus for these SeqCalling assemblies. These sequences were analyzed for putative coding regions as well as for similarity to the known DNA and protein sequences. Programs used for these analyses include Grail, Genscan, BLAST, HMMER, FASTA, Hybrid and other relevant programs.


[2306] Some additional genomic regions may have also been identified because selected SeqCalling assemblies map to those regions. Such SeqCalling sequences may have overlapped with regions defined by homology or exon prediction. They may also be included because the location of the fragment was in the vicinity of genomic regions identified by similarity or exon prediction that had been included in the original predicted sequence. The sequence so identified was manually assembled and then may have been extended using one or more additional sequences taken from CuraGen Corporation's human SeqCalling database. SeqCalling fragments suitable for inclusion were identified by the CuraTools™ program SeqExtend or by identifying SeqCalling fragments mapping to the appropriate regions of the genomic clones analyzed.


[2307] The regions defined by the procedures described above were then manually integrated and corrected for apparent inconsistencies that may have arisen, for example, from miscalled bases in the original fragments or from discrepancies between predicted exon junctions, EST locations and regions of sequence similarity, to derive the final sequence disclosed herein. When necessary, the process to identify and analyze SeqCalling assemblies and genomic clones was reiterated to derive the full length sequence (Alderborn et al., Determination of Single Nucleotide Polymorphisms by Real-time Pyrophosphate DNA Sequencing. Genome Research. 10 (8) 1249-1265, 2000).


[2308] Variants are reported individually but any combination of all or a select subset of variants are also included as contemplated NOVX embodiments of the invention.


[2309] NOV5a has one SNP variant, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs:13 and 14, respectively. The nucleotide sequence of the NOV5a variant differs as shown in Table SNP1.
1069TABLE SNP1NOV5a variants.NucleotidesAmino AcidsPosi-Modi-Posi-Modi-VarianttionInitialfiedtionInitialfied13376274143AT47GlnLeu


[2310] NOV9a has eight SNP variants, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs:21 and 22, respectively. The nucleotide sequence of the NOV9a variant differs as shown in Table SNP2.
1070TABLE SNP2NOV9a variants.NucleotidesAmino AcidsPosi-Modi-Posi-Modi-VarianttionInitialfiedtionInitialfied13376043230GT72GluEnd13376044341GA109GlyArg13376045441AC142GlnPro13376046532CT172HisHis133760501680TC555LeuSer13376O491762GT582LeuPhe133760481818CT601SerLeu133760471900AG628ThrThr


[2311] NOV14a has five SNP variants, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs:43 and 44, respectively. The nucleotide sequence of the NOV14a variant differs as shown in Table SNP3.
1071TABLE SNP3NOV14a variants.NucleotidesAmino AcidsPosi-Modi-Posi-Modi-VarianttionInitialfiedtionInitialfied133764381307TC431ValAla133764371571AG519HisArg133764361625TC537ValAla133764351646TC544ValAla133764341667TC551IleThr


[2312] NOV15a has twelve SNP variants, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs:53 and 54, respectively. The nucleotide sequence of the NOV14a variant differs as shown in Table SNP4.
1072TABLE SNP4NOV15a variants.NucleotidesAmino AcidsPosi-Modi-Posi-Modi-VarianttionInitialfiedtionInitialfied13376083154AG45ProPro13376082194TC59SerPro13376081253GA78ArgArg13376080280GA87GlnGln13376079327CT103AlaVal13376078338CT107ProSer13376077366TC116IleThr13376076502AG161LysLys133760691069AG350ProPro133760721137AG373GluGly133760711264TC415LeuLeu133760701367TC450SerPro


[2313] NOV17a has four SNP variants, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs:61 and 62, respectively. The nucleotide sequence of the NOV17a variant differs as shown in Table SNP5.
1073TABLE SNP5NOV17a variants.NucleotidesAmino AcidsPosi-Modi-Posi-Modi-VarianttionInitialfiedtionInitialfied13377433175TC55HisHis13377432223CG71ProPro13377431538GA176ThrThr13377430680TC224PheLeu


[2314] NOV19a has one SNP variant, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs:71 and 72, respectively. The nucleotide sequence of the NOV19a variant differs as shown in Table SNP6.
1074TABLE SNP6NOV19a variants.NucleotidesAmino AcidsPosi-Modi-Posi-Modi-VarianttionInitialfiedtionInitialfied133774341777TA586ThrThr


[2315] NOV21a has one SNP variant, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs:75 and 76, respectively. The nucleotide sequence of the NOV21a variant differs as shown in Table SNP7.
1075TABLE SNP7NOV21a variants.NucleotidesAmino AcidsPosi-Modi-Posi-Modi-VarianttionInitialfiedtionInitialfied133774357503TA2482AlaAla


[2316] NOV38a has two SNP variants, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs:123 and 124, respectively. The nucleotide sequence of the NOV38a variant differs as shown in Table SNP8.
1076TABLE SNP8NOV38a variants.NucleotidesAmino AcidsVariantPositionInitialModifiedPositionInitialModified13377439801GA232SerSer133774411595CG497ProArg


[2317] NOV39a has three SNP variants, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs:125 and 126, respectively. The nucleotide sequence of the NOV39a variant differs as shown in Table SNP9.
1077TABLE SNP9NOV39a variants.NucleotidesAmino AcidsPosi-Modi-Posi-Modi-VarianttionInitialfiedtionInitialfied13375670183CG57HisGln13375669187CT59LeuPhe133773891385AG458HisArg


[2318] NOV46a has four SNP variants, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs:143 and 144, respectively. The nucleotide sequence of the NOV46a variant differs as shown in Table SNP10.
1078TABLE SNP10NOV46a variants.NucleotidesAmino AcidsPosi-Modi-Posi-Modi-VarianttionInitialfiedtionInitialfied13377442177TC27ValAla13377443590AG165ThrAla13377444799AG234GlnGln13377445977TC294TyrHis


[2319] NOV49a has two SNP variants, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs:151 and 152, respectively. The nucleotide sequence of the NOV49a variant differs as shown in Table SNP11.
1079TABLE SNP11NOV49a variants.NucleotidesAmino AcidsPosi-Modi-Posi-Modi-VarianttionInitialfiedtionInitialfied13377450119AG7ArgGly133774481556GA486AlaThr


[2320] NOV50a has one SNP variant, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs:153 and 154, respectively. The nucleotide sequence of the NOV50a variant differs as shown in Table SNP 12.
1080TABLE SNP12NOV50a variants.NucleotidesAmino AcidsPosi-Modi-Posi-Modi-VarianttionInitialfiedtionInitialfied133774512371GA791AlaThr


[2321] NOV51a has five SNP variants, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs:155 and 156, respectively. The nucleotide sequence of the NOV51a variant differs as shown in Table SNP13.
1081TABLE SNP13NOV51a variants.NucleotidesAmino AcidsPosi-Modi-Posi-Modi-VarianttionInitialfiedtionInitialfied13374492765GA243AlaThr13374491924TC296PheLeu133774531028CT330ProPro133774541052AC338AlaAla133774551205CT389HisHis


[2322] NOV52a has one SNP variant, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs:157 and 158, respectively. The nucleotide sequence of the NOV52a variant differs as shown in Table SNP14.
1082TABLE SNP14NOV52a variants.NucleotidesAmino AcidsPosi-Modi-Posi-Modi-VarianttionInitialfiedtionInitialfied13377458221CT37ArgTrp


[2323] NOV55a has one SNP variant, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs:163 and 164, respectively. The nucleotide sequence of the NOV55a variant differs as shown in Table SNP15.
1083TABLE SNP15NOV55a variants.NucleotidesAmino AcidsPosi-Modi-Posi-Modi-VarianttionInitialfiedtionInitialfied13377462514CT165ArgTrp13377461993TC324SerSer


[2324] NOV60a has one SNP variant, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs:183 and 184, respectively. The nucleotide sequence of the NOV55a variant differs as shown in Table SNP16.
1084TABLE SNP16NOV60a variants.NucleotidesAmino AcidsPosi-Modi-Posi-Modi-VarianttionInitialfiedtionInitialfied13377463453TC111GlyGly


[2325] NOV65a has one SNP variant, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs:195 and 196, respectively. The nucleotide sequence of the NOV65a variant differs as shown in Table SNP17.
1085TABLE SNP17NOV65a variants.NucleotidesAmino AcidsPosi-Modi-Posi-Modi-VarianttionInitialfiedtionInitialfied1337746475CA25GlnLys


[2326] NOV68a has one SNP variant, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs:201 and 202, respectively. The nucleotide sequence of the NOV68a variant differs as shown in Table SNP 18.
1086TABLE SNP18NOV68a variants.NucleotidesAmino AcidsPosi-Modi-Posi-Modi-VarianttionInitialfiedtionInitialfied13377465438CG145GlyGly


[2327] NOV72a has one SNP variant, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs:209 and 210, respectively. The nucleotide sequence of the NOV72a variant differs as shown in Table SNP19.
1087TABLE SNP19NOV72a variants.NucleotidesAmino AcidsPosi-Modi-Posi-Modi-VarianttionInitialfiedtionInitialfied13377466839CT271ProSer


[2328] NOV80a has four SNP variants, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs:225 and 226, respectively. The nucleotide sequence of the NOV80a variant differs as shown in Table SNP20.
1088TABLE SNP20NOV80a variants.NucleotidesAmino AcidsPosi-Modi-Posi-Modi-VarianttionInitialfiedtionInitialfied13377471166GT46AlaSer13377470482CT151AlaVal13377469685AG219ThrAla133774681410GC460GluAsp


[2329] NOV81a has four SNP variants, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs:229 and 230, respectively. The nucleotide sequence of the NOV81a variant differs as shown in Table SNP21.
1089TABLE SNP21NOV81a variants.NucleotidesAmino AcidsPosi-Modi-Posi-Modi-VarianttionInitialfiedtionInitialfied13377472285CT91HisTyr13377473553AG180HisArg13377474554CT180HisHis133774752581AG856GlnArg


[2330] NOV89a has two SNP variants, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs:249 and 250, respectively. The nucleotide sequence of the NOV89a variant differs as shown in Table SNP22.
1090TABLE SNP22NOV89a variants.NucleotidesAmino AcidsPosi-Modi-Posi-Modi-VarianttionInitialfiedtionInitialfied13377477425AG119MetVal133774781162CA364ValVal


[2331] NOV94a has one SNP variants, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs:269 and 270, respectively. The nucleotide sequence of the NOV94a variant differs as shown in Table SNP23.
1091TABLE SNP23NOV94a variants.NucleotidesAmino AcidsPosi-Modi-Posi-Modi-VarianttionInitialfiedtionInitialfied133774791005TC303AspAsp


[2332] NOV96a has two SNP variants, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs:273 and 274, respectively. The nucleotide sequence of the NOV96a variant differs as shown in Table SNP24.
1092TABLE SNP24NOV96a variants.NucleotidesAmino AcidsPosi-Modi-Posi-Modi-VarianttionInitialfiedtionInitialfied13377480150AG45LysArg133774822221AG735SerSer


[2333] NOV99a has one SNP variant, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs:283 and 284, respectively. The nucleotide sequence of the NOV99a variant differs as shown in Table SNP25.
1093TABLE SNP25NOV99a variants.NucleotidesAmino AcidsPosi-Modi-Posi-Modi-VarianttionInitialfiedtionInitialfied13377485274TC78ThrThr


[2334] NOV105a has three SNP variants, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs:299 and 300, respectively. The nucleotide sequence of the NOV105a variant differs as shown in Table SNP26.
1094TABLE SNP26NOV105a variants.NucleotidesAmino AcidsPosi-Modi-Posi-Modi-VarianttionInitialfiedtionInitialfied13377488453CT145IleIle13377487828TG270ThrThr13377486924AG302ThrThr


[2335] NOV113a has three SNP variants, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs:315 and 316, respectively. The nucleotide sequence of the NOV113a variant differs as shown in Table SNP27.
1095TABLE SNP27NOV113a variants.NucleotidesAmino AcidsPosi-Modi-Posi-Modi-VarianttionInitialfiedtionInitialfied13377490 340GA100AlaThr13377491 659CT206ProLeu13377492 726CT228ArgArg13377493 915TC291AlaAla133774941058TC339IleThr133774951088TC349LeuPro


[2336] NOV114a has two SNP variants, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs:319 and 320, respectively. The nucleotide sequence of the NOV114a variant differs as shown in Table SNP28.
1096TABLE SNP28NOV114a variants.NucleotidesAmino AcidsPosi-Modi-Posi-Modi-VarianttionInitialfiedtionInitialfied13375633185TC 54ValAla13375632689AG222Gln Arg


[2337] NOV116a has two SNP variants, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs:325 and 326, respectively. The nucleotide sequence of the NOV116a variant differs as shown in Table SNP29.
1097TABLE SNP29NOV116a variants.NucleotidesAmino AcidsPosi-Modi-Posi-Modi-VarianttionInitialfiedtionInitialfied13374815203AG 63ThrAla13374814384TC123LeuPro


[2338] NOV117a has three SNP variants, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs:329 and 330, respectively. The nucleotide sequence of the NOV117a variant differs as shown in Table SNP30.
1098TABLE SNP30NOV117a variants.NucleotidesAmino AcidsPosi-Modi-Posi-Modi-VarianttionInitialfiedtionInitialfied13377507 453AG149ProPro13377506 755AT250GluVal133775051128GA374LysLys


[2339] NOV124a has six SNP variants, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs:343 and 344, respectively. The nucleotide sequence of the NOV124a variant differs as shown in Table SNP31.
1099TABLE SNIP31NOV124a variants.NucleotidesAmino AcidsPosi-Modi-Posi-Modi-VarianttionInitialfiedtionInitialfied13377511 186CT 39SerSer13377512 372CT101GlyGly13377513 970GT301AspTyr133775141051GA328ValMet133775151266CT399IleIle133775161304AG412AspGly


[2340] NOV126a has two SNP variants, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs:349 and 350, respectively. The nucleotide sequence of the NOV126a variant differs as shown in Table SNP32.
1100TABLE SNP32NOV126a variants.NucleotidesAmino AcidsPosi-Modi-Posi-Modi-VarianttionInitialfiedtionInitialfied13377517747TC234CysCys



Other Embodiments

[2341] Although particular embodiments have been disclosed herein in detail, this has been done by way of example for purposes of illustration only, and is not intended to be limiting with respect to the scope of the appended claims, which follow. In particular, it is contemplated by the inventors that various substitutions, alterations, and modifications may be made to the invention without departing from the spirit and scope of the invention as defined by the claims. The choice of nucleic acid starting material, clone of interest, or library type is believed to be a matter of routine for a person of ordinary skill in the art with knowledge of the embodiments described herein. Other aspects, advantages, and modifications considered to be within the scope of the following claims. The claims presented are representative of the inventions disclosed herein. Other, unclaimed inventions are also contemplated. Applicants reserve the right to pursue such inventions in later claims.


Claims
  • 1. An isolated polypeptide comprising an amino acid sequence selected from the group consisting of: a) a mature form of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 178; b) a variant of a mature form of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 178, wherein any amino acid in the mature form is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed; c) the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 178; d) a variant of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 178 wherein any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed; and e) a fragment of any of a) through d).
  • 2. The polypeptide of claim 1 that is a naturally occurring allelic variant of the sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 178.
  • 3. The polypeptide of claim 2, wherein said allelic variant comprises an amino acid sequence that is the translation of a nucleic acid sequence differing by a single nucleotide from a nucleic acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 178.
  • 4. The polypeptide of claim 1 that is a variant polypeptide described therein, wherein any amino acid specified in the chosen sequence is changed to provide a conservative substitution.
  • 5. A method for determining the presence or amount of the polypeptide of claim 1 in a sample, the method comprising: (a) providing said sample; (b) introducing said sample to an antibody that binds immunospecifically to the polypeptide; and (c) determining the presence or amount of antibody bound to said polypeptide, thereby determining the presence or amount of polypeptide in said sample.
  • 6. A method for determining the presence of or predisposition to a disease associated with altered levels of the polypeptide of claim 1 in a first mammalian subject, the method comprising: a) measuring the level of expression of the polypeptide in a sample from the first mammalian subject; and b) comparing the amount of said polypeptide in the sample of step (a) to the amount of the polypeptide present in a control sample from a second mammalian subject known not to have, or not to be predisposed to, said disease, wherein an alteration in the expression level of the polypeptide in the first subject as compared to the control sample indicates the presence of or predisposition to said disease.
  • 7. A method of identifying an agent that binds to the polypeptide of claim 1, the method comprising: (a) introducing said polypeptide to said agent; and (b) determining whether said agent binds to said polypeptide.
  • 8. The method of claim 7 wherein the agent is a cellular receptor or a downstream effector.
  • 9. A method for identifying a potential therapeutic agent for use in treatment of a pathology, wherein the pathology is related to aberrant expression or aberrant physiological interactions of the polypeptide of claim 1, the method comprising: (a) providing a cell expressing the polypeptide of claim 1 and having a property or function ascribable to the polypeptide; (b) contacting the cell with a composition comprising a candidate substance; and (c) determining whether the substance alters the property or function ascribable to the polypeptide; whereby, if an alteration observed in the presence of the substance is not observed when the cell is contacted with a composition devoid of the substance, the substance is identified as a potential therapeutic agent.
  • 10. A method for screening for a modulator of activity or of latency or predisposition to a pathology associated with the polypeptide of claim 1, said method comprising: a) administering a test compound to a test animal at increased risk for a pathology associated with the polypeptide of claim 1, wherein said test animal recombinantly expresses the polypeptide of claim 1;b) measuring the activity of said polypeptide in said test animal after administering the compound of step (a); and c) comparing the activity of said protein in said test animal with the activity of said polypeptide in a control animal not administered said polypeptide, wherein a change in the activity of said polypeptide in said test animal relative to said control animal indicates the test compound is a modulator of latency of, or predisposition to, a pathology associated with the polypeptide of claim 1.
  • 11. The method of claim 10, wherein said test animal is a recombinant test animal that expresses a
  • 12. A method for modulating the activity of the polypeptide of claim 1, the method comprising introducing a cell sample expressing the polypeptide of said claim with a compound that binds to said polypeptide in an amount sufficient to modulate the activity of the polypeptide.
  • 13. An isolated nucleic acid molecule comprising a nucleic acid sequence encoding a polypeptide comprising an amino acid sequence selected from the group consisting of: a) a mature form of the amino acid sequence given SEQ ID NO: 2n, wherein n is an integer between 1 and 178; b) a variant of a mature form of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 178 wherein any amino acid in the mature form of the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed; c) the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 178; d) a variant of the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 178, in which any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed; e) a nucleic acid fragment encoding at least a portion of a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 178 or any variant of said polypeptide wherein any amino acid of the chosen sequence is changed to a different amino acid, provided that no more than 10% of the amino acid residues in the sequence are so changed; and f) the complement of any of said nucleic acid molecules.
  • 14. The nucleic acid molecule of claim 13, wherein the nucleic acid molecule comprises the nucleotide sequence of a naturally occurring allelic nucleic acid variant.
  • 15. The nucleic acid molecule of claim 13 that encodes a variant polypeptide, wherein the variant polypeptide has the polypeptide sequence of a naturally occurring polypeptide variant.
  • 16. The nucleic acid molecule of claim 13, wherein the nucleic acid molecule differs by a single nucleotide from a nucleic acid sequence selected from the group consisting of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178.
  • 17. The nucleic acid molecule of claim 13, wherein said nucleic acid molecule comprises a nucleotide sequence selected from the group consisting of a) the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178; b) a nucleotide sequence wherein one or more nucleotides in the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178 is changed from that selected from the group consisting of the chosen sequence to a different nucleotide provided that no more than 15% of the nucleotides are so changed; c) a nucleic acid fragment of the sequence selected from the group consisting of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178; and d) a nucleic acid fragment wherein one or more nucleotides in the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178 is changed from that selected from the group consisting of the chosen sequence to a different nucleotide provided that no more than 15% of the nucleotides are so changed.
  • 18. The nucleic acid molecule of claim 13, wherein said nucleic acid molecule hybridizes under stringent conditions to the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178, or a complement of said nucleotide sequence.
  • 19. The nucleic acid molecule of claim 13, wherein the sequence is changed such that no more than 15% of the nucleotides in the coding sequence differ from the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 178 or a fragment thereof.
  • 20. A vector comprising the nucleic acid molecule of claim 19.
  • 21. The vector of claim 20, further comprising a promoter operably linked to said nucleic acid molecule.
  • 22. A cell comprising the vector of claim 20.
  • 23. A method for determining the presence or amount of the nucleic acid molecule of claim 13 in a sample, the method comprising: (a) providing said sample; (b) introducing said sample to a probe that binds to said nucleic acid molecule; and (c) determining the presence or amount of said probe bound to said nucleic acid molecule, thereby determining the presence or amount of the nucleic acid molecule in said sample.
  • 24. The method of claim 23 wherein presence or amount of the nucleic acid molecule is used as a marker for cell or tissue type.
  • 25. The method of claim 24 wherein the cell or tissue type is cancerous.
  • 26. A method for determining the presence of or predisposition to a disease associated with altered levels of the nucleic acid molecule of claim 13 in a first mammalian subject, the method comprising: a) measuring the amount of the nucleic acid in a sample from the first mammalian subject; and b) comparing the amount of said nucleic acid in the sample of step (a) to the amount of the nucleic acid present in a control sample from a second mammalian subject known not to have or not be predisposed to, the disease; wherein an alteration in the level of the nucleic acid in the first subject as compared to the control sample indicates the presence of or predisposition to the disease.
RELATED APPLICATIONS

[0001] This is a request for filing a new nonprovisional application under 37 C.F.R. §1.53(b). This application claims priority to U.S. S. No. 60/274,322 filed on Mar. 8, 2001 (Cura 590); U.S. S. No. 60/283,675 filed on Apr. 13, 2001 (Cura 590D1); U.S. S. No. 60/338,092 filed on Dec. 3, 2001 (Cura 590D2); U.S. S. No. 60/274,281 filed on Mar. 8, 2001 (Cura 591); U.S. S. No. 60/274,101 filed on Mar. 8, 2001 (Cura 592); U.S. S. No. 60/325,681 filed on Sep. 27, 2001 (Cura 592J1); U.S. S. No. 60/304,354 filed on Jul. 10, 2001 (Cura 592I1); U.S. S. No. 60/279,995 filed on Mar. 30, 2001 (Cura 592H1); U.S. S. No. 60/294,899 filed on May 31, 2001 (Cura 592E1); U.S. S. No. 60/287,424 filed on Apr. 30, 2001 (Cura 592D1); U.S. S. No. 60/299,027 filed on Jun. 18, 2001 (Cura 592D2); U.S. S. No. 60/309,198 filed on Jul. 31, 2001 (Cura 592C1); U.S. S. No. 60/281,194 filed on Apr. 4, 2001 (Cura 592A1); U.S. S. No. 60/274,194 filed on Mar. 8, 2001 (Cura 593); U.S. S. No. 60/274,849 filed on Mar. 9, 2001 (Cura 594); U.S. S. No. 60/330,380 filed on Oct. 18, 2001 (Cura 594C1); U.S. S. No. 60/275,235 filed on Mar. 12, 2001 (Cura 595); U.S. S. No. 60/288,342 filed on May 3, 2001 (Cura 595J1); U.S. S. No. 60/275,578 filed on Mar. 13, 2001 (Cura 596); U.S. S. No. 60/291,240 filed on May 16, 2001 (Cura 596I1); U.S. S. No. 60/294,485 filed on May 30, 2001 (Cura 596B1); U.S. S. No. 60/299,310 filed on Jun. 19, 2001 (Cura 596A1); U.S. S. No. 60/275,579 filed on Mar. 13, 2001 (Cura 597); U.S. S. No. 60/275,601 filed on Mar. 13, 2001 (Cura 598); U.S. S. No. 60/276,000 filed on Mar. 14, 2001 (Cura 599); U.S. S. No. 60/280,900 filed on Apr. 2, 2001 (Cura 599E1); U.S. S. No. 60/276,776 filed on Mar. 16, 2001 (Cura 600); U.S. S. No. 60/294,889 filed on May 31, 2001 (Cura 600G 1); U.S. S. No. 60/318,770 filed on Sep. 12, 2001 (Cura 600E1); U.S. S. No. 60/276,994 filed on Mar. 19, 2001 (Cura 604); U.S. S. No. 60/277,338 filed on Mar. 20, 2001 (Cura 607); U.S. S. No. 60/325,430 filed on Sep. 27, 2001 (Cura 607J1); U.S. S. No. 60/332,094 filed on Nov. 21, 2001 (Cura 607C1); U.S. S. No. 60/299,303 filed on Jun. 19, 2001 (Cura 607B1); U.S. S. No. 60/288,066 filed on May 2, 2001 (Cura 607A1); U.S. S. No. 60/277,321 filed on Mar. 20, 2001 (Cura 608); U.S. S. No. 60/280,822 filed on Apr. 2, 2001 (Cura 608A); U.S. S. No. 60/277,239 filed on Mar. 20, 2001 (Cura 609); U.S. S. No. 60/277,327 filed on Mar. 20, 2001 (Cura 610); U.S. S. No. 60/277,791 filed on Mar. 21, 2001 (Cura 611); U.S. S. No. 60/333,184 filed on Nov. 14, 2001 (Cura 611H1); U.S. S. No. 60/277,833 filed on Mar. 22, 2001 (Cura 612); U.S. S. No. 60/318,462 filed on Sep. 10, 2001 (Cura 612J1); U.S. S. No. 60/288,528 filed on May 3, 2001 (Cura 612A1); U.S. S. No. 60/278,152 filed on Mar. 23, 2001 (Cura 613); U.S. S. No. 60/332,272 filed on Nov. 14, 2001 (Cura 613D1); U.S. S. No. 60/278,894 filed on Mar. 26, 2001 (Cura 614); U.S. S. No. 60/312,903 filed on Aug. 16, 2001 (Cura 614C1); U.S. S. No. 60/333,272 filed on Nov. 14, 2001 (Cura 614C2); U.S. S. No. 60/279,036 filed on Mar. 27, 2001 (Cura 615); U.S. S. No. 60/332,172 filed on Nov. 14, 2001 (Cura 615I1); U.S. S. No. 60/337,426 filed on Dec. 3, 2001 (Cura 615I2); U.S. S. No. 60/278,999 filed on Mar. 27, 2001 (Cura 616); U.S. S. No. 60/279,344 filed on Mar. 28, 2001 (Cura 617); U.S. S. No. 60/332,271 filed on Nov. 14, 2001 (Cura 617J1); U.S. S. No. 60/291,099 filed on May 16, 2001 (Cura 617H1); U.S. S. No. 60/291,190 filed on May 15, 2001 (Cura 617E1); U.S. S. No. 60/280,233 filed on Mar. 30, 2001 (Cura 618); U.S. S. No. 60/280,802 filed on Apr. 2, 2001 (Cura 621); U.S. S. No. 60/335,301 filed on Oct. 31, 2001 (Cura 621 F1); U.S. S. No. 60/337,185 filed on Dec. 4, 2001 (Cura 621D1); and U.S. S. No. 60/345,705 filed on Jan. 3, 2002 (Cura 621B1).

Provisional Applications (62)
Number Date Country
60274322 Mar 2001 US
60283675 Apr 2001 US
60338092 Dec 2001 US
60274281 Mar 2001 US
60274191 Mar 2001 US
60325681 Sep 2001 US
60304354 Jul 2001 US
60279995 Mar 2001 US
60294899 May 2001 US
60287424 Apr 2001 US
60299027 Jun 2001 US
60309198 Jul 2001 US
60281444 Apr 2001 US
60274194 Mar 2001 US
60274849 Mar 2001 US
60330380 Oct 2001 US
60275235 Mar 2001 US
60288342 May 2001 US
60275578 Mar 2001 US
60291240 May 2001 US
60294485 May 2001 US
60299310 Jun 2001 US
60275579 Mar 2001 US
60275601 Mar 2001 US
60276000 Mar 2001 US
60280900 Apr 2001 US
60276776 Mar 2001 US
60294889 May 2001 US
60318770 Sep 2001 US
60276994 Mar 2001 US
60277338 Mar 2001 US
60325430 Sep 2001 US
60332094 Nov 2001 US
60299303 Jun 2001 US
60288066 May 2001 US
60277321 Mar 2001 US
60280822 Apr 2001 US
60277239 Mar 2001 US
60277327 Mar 2001 US
60277791 Mar 2001 US
60333184 Nov 2001 US
60277833 Mar 2001 US
60318462 Sep 2001 US
60288528 May 2001 US
60278152 Mar 2001 US
60332272 Nov 2001 US
60278894 Mar 2001 US
60312903 Aug 2001 US
60333272 Nov 2001 US
60279036 Mar 2001 US
60332172 Nov 2001 US
60337426 Dec 2001 US
60278999 Mar 2001 US
60279344 Mar 2001 US
60332271 Nov 2001 US
60291099 May 2001 US
60291190 May 2001 US
60280233 Mar 2001 US
60280802 Apr 2001 US
60335301 Oct 2001 US
60337185 Dec 2001 US
60345705 Jan 2002 US