Novel Human proteins, polynucleotides encoding them and methods of using the same

Abstract

Disclosed are polypeptides and nucleic acids encoding same. Also disclosed are vectors, host cells, antibodies and recombinant methods for producing the polypeptides and polynucleotides, as well as methods for using same.

Description

FIELD OF THE INVENTION

[0002] The present invention is based in part on nucleic acids encoding proteins that are new members of the following protein families: Leucine Rich Repeat-like Homo sapiens proteins, Leucine Rich Repeat proteins, Adenine Nucleotide Translocator 2 (ADP/ATP Translocase 2)-like Homo sapiens proteins, Mitochondrial energy transfer protein domain-like Homo sapiens proteins, ATRAP-like Homo sapiens proteins, Cytosolic phosphoprotein proteins, PAX 3A-like Homo sapiens proteins, GRP-1-Associated Scaffold Protein GRASP proteins, Neurabin 1-like Homo sapiens proteins, Epidermal fatty acid binding protein-like Homo sapiens proteins, Septin 6 (KIAA0128)-like Homo sapiens proteins, RIM2-4C-like Homo sapiens proteins, Cell Growth Regulator Falkor-like Homo sapiens-like proteins, Meningioma-Expressed Antigen 6/11 (MEA6) (MEA11)-like Homo sapiens proteins, Liprin alpha 4-like Homo sapiens proteins, Q9GKW8-like Homo sapiens proteins, GTPase Activator Protein-like Homo sapiens proteins, PEFLIN-like Homo sapiens proteins, Neurotransmitter-gated ion-channel-like Homo sapiens proteins, Carboxyl-Terminal PDZ Ligand of Neuronal Nitric Oxide Synthase-like Homo sapiens proteins, Amyloid Beta A4 Precursor Protein-Binding Family B Member 2-like Homo sapiens proteins, Calreticulin Precursor-like Homo sapiens proteins, Protein Kinase C Inhibitor-like Homo sapiens proteins, PAX Transcription Activation Domain Interacting Protein PTIP-like Homo sapiens proteins, MAP1 Light Chain 3 Related Protein-like Homo sapiens proteins, Intacellular signaling protein-like Homo sapiens proteins, FISH Protein-like Homo sapiens proteins, profilaggrin-like Homo sapiens proteins, VP3 domain-containing protein-like Homo sapiens proteins, VP3 domain-containing protein-like proteins, PX19-like Homo sapiens proteins, Polyubiquitin-like Homo sapiens proteins, Pathcalling Protein-like Homo sapiens proteins, MYND zinc finger (ZnF) domain-containing protein-like Homo sapiens proteins, Q9N061-like Homo sapiens proteins, Stra8-like Homo sapiens proteins, Membrane Protein Kinase-like Homo sapiens proteins, and Delta 4 3-Oxosteroid 5 Beta Reductase-like Homo sapiens proteins.

[0003] The invention relates to polynucleotides and the polypeptides encoded by such polynucleotides, as well as vectors, host cells, antibodies and recombinant methods for producing the polypeptides and polynucleotides, as well as methods for using the same.

BACKGROUND OF THE INVENTION

[0004] The invention generally relates to nucleic acids and polypeptides encoded therefrom. More specifically, the invention relates to nucleic acids encoding cytoplasmic, nuclear, membrane bound, and secreted polypeptides, as well as vectors, host cells, antibodies, and recombinant methods for producing these nucleic acids and polypeptides.

SUMMARY OF THE INVENTION

[0005] The present invention is based in part on nucleic acids encoding proteins that are members of the following protein families: Leucine Rich Repeat-like Homo sapiens proteins, Leucine Rich Repeat proteins, Adenine Nucleotide Translocator 2 (ADP/ATP Translocase 2)-like Homo sapiens proteins, Mitochondrial energy transfer protein domain-like Homo sapiens proteins, ATRAP-like Homo sapiens proteins, Cytosolic phosphoprotein proteins, PAX 3A-like Homo sapiens proteins, GRP-1-Associated Scaffold Protein GRASP proteins, Neurabin 1-like Homo sapiens proteins, Epidermal fatty acid binding protein-like Homo sapiens proteins, Septin 6 (KIAA0128)-like Homo sapiens proteins, RIM2-4C-like Homo sapiens proteins, Cell Growth Regulator Falkor-like Homo sapiens-like proteins, Meningioma-Expressed Antigen 6/11 (MEA6) (MEA11)-like Homo sapiens proteins, Liprin alpha 4-like Homo sapiens proteins, Q9GKW8-like Homo sapiens proteins, GTPase Activator Protein-like Homo sapiens proteins, PEFLIN-like Homo sapiens proteins, Neurotransmitter-gated ion-channel-like Homo sapiens proteins, Carboxyl-Terminal PDZ Ligand of Neuronal Nitric Oxide Synthase-like Homo sapiens proteins, Amyloid Beta A4 Precursor Protein-Binding Family B Member 2-like Homo sapiens proteins, Calreticulin Precursor-like Homo sapiens proteins, Protein Kinase C Inhibitor-like Homo sapiens proteins, PAX Transcription Activation Domain Interacting Protein PTIP-like Homo sapiens proteins, MAP1 Light Chain 3 Related Protein-like Homo sapiens proteins, Intacellular signaling protein-like Homo sapiens proteins, FISH Protein-like Homo sapiens proteins, profilaggrin-like Homo sapiens proteins, VP3 domain-containing protein-like Homo sapiens proteins, VP3 domain-containing protein-like proteins, PX19-like Homo sapiens proteins, Polyubiquitin-like Homo sapiens proteins, Pathcalling Protein-like Homo sapiens proteins, MYND zinc finger (ZnF) domain-containing protein-like Homo sapiens proteins, Q9N061-like Homo sapiens proteins, Stra8-like Homo sapiens proteins, Membrane Protein Kinase-like Homo sapiens proteins, and Delta 4 3-Oxosteroid 5 Beta Reductase-like Homo sapiens proteins. The novel polynucleotides and polypeptides are referred to herein as NOV1a, NOV2a, NOV3a, NOV4a, NOV5a, NOV6a, NOV7a, NOV8a, NOV9a, NOV10a, NOV11a, NOV12a, NOV13a, NOV14a, NOV15a, NOV16a, NOV17a, NOV18a, NOV19a, NOV20a, NOV21a, NOV22a, NOV23a, NOV24a, NOV24b, NOV24c, NOV25a, NOV26a, NOV27a, NOV28a, NOV29a, NOV30a, NOV31a, NOV31b, NOV32a, NOV33a, NOV34a, NOV35a, NOV36a, NOV36b, NOV37a, NOV37b, NOV38a and NOV39a. These nucleic acids and polypeptides, as well as derivatives, homologs, analogs and fragments thereof, will hereinafter be collectively designated as “NOVX” nucleic acid or polypeptide sequences.

[0006] In one aspect, the invention provides an isolated NOVX nucleic acid molecule encoding a NOVX polypeptide that includes a nucleic acid sequence that has identity to the nucleic acids disclosed in SEQ ID NO:2n-1, wherein n is an integer between 1 and 44. In some embodiments, the NOVX nucleic acid molecule will hybridize under stringent conditions to a nucleic acid sequence complementary to a nucleic acid molecule that includes a protein-coding sequence of a NOVX nucleic acid sequence. The invention also includes an isolated nucleic acid that encodes a NOVX polypeptide, or a fragment, homolog, analog or derivative thereof. For example, the nucleic acid can encode a polypeptide at least 80% identical to a polypeptide comprising the amino acid sequences of SEQ ID NO:2n, wherein n is an integer between 1 and 44. The nucleic acid can be, for example, a genomic DNA fragment or a CDNA molecule that includes the nucleic acid sequence of any of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44.

[0007] Also included in the invention is an oligonucleotide, e.g., an oligonucleotide which includes at least 6 contiguous nucleotides of a NOVX nucleic acid (e.g., SEQ ID NO:2n-1, wherein n is an integer between 1 and 44) or a complement of said oligonucleotide. Also included in the invention are substantially purified NOVX polypeptides (SEQ ID NO:2n, wherein n is an integer between 1 and 44). In certain embodiments, the NOVX polypeptides include an amino acid sequence that is substantially identical to the amino acid sequence of a human NOVX polypeptide.

[0008] The invention also features antibodies that immunoselectively bind to NOVX polypeptides, or fragments, homologs, analogs or derivatives thereof.

[0009] In another aspect, the invention includes pharmaceutical compositions that include therapeutically- or prophylactically-effective amounts of a therapeutic and a pharmaceutically-acceptable carrier. The therapeutic can be, e.g., a NOVX nucleic acid, a NOVX polypeptide, or an antibody specific for a NOVX polypeptide. In a further aspect, the invention includes, in one or more containers, a therapeutically- or prophylactically-effective amount of this pharmaceutical composition.

[0010] In a further aspect, the invention includes a method of producing a polypeptide by culturing a cell that includes a NOVX nucleic acid, under conditions allowing for expression of the NOVX polypeptide encoded by the DNA. If desired, the NOVX polypeptide can then be recovered.

[0011] In another aspect, the invention includes a method of detecting the presence of a NOVX polypeptide in a sample. In the method, a sample is contacted with a compound that selectively binds to the polypeptide under conditions allowing for formation of a complex between the polypeptide and the compound. The complex is detected, if present, thereby identifying the NOVX polypeptide within the sample.

[0012] The invention also includes methods to identify specific cell or tissue types based on their expression of a NOVX.

[0013] Also included in the invention is a method of detecting the presence of a NOVX nucleic acid molecule in a sample by contacting the sample with a NOVX nucleic acid probe or primer, and detecting whether the nucleic acid probe or primer bound to a NOVX nucleic acid molecule in the sample.

[0014] In a further aspect, the invention provides a method for modulating the activity of a NOVX polypeptide by contacting a cell sample that includes the NOVX polypeptide with a compound that binds to the NOVX polypeptide in an amount sufficient to modulate the activity of said polypeptide. The compound can be, e.g., a small molecule, such as a nucleic acid, peptide, polypeptide, peptidomimetic, carbohydrate, lipid or other organic (carbon containing) or inorganic molecule, as further described herein.

[0015] In another embodiment, the invention involves 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 polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 44, the method including providing a cell expressing the polypeptide of the invention 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.

[0016] Also within the scope of the invention is the use of a therapeutic in the manufacture of a medicament for treating or preventing disorders or syndromes including, e.g., adrenoleukodystrophy, congenital adrenal hyperplasia, hemophilia, hypercoagulation, idiopathic thrombocytopenic purpura, autoimmune disease, allergies, immunodeficiencies, Von Hippel-Lindau (VHL) syndrome, Alzheimer's disease, stroke, tuberous sclerosis, hypercalcemia, Parkinson's disease, Huntington's disease, cerebral palsy, epilepsy, Lesch-Nyhan syndrome, multiple sclerosis, ataxia-telangiectasia, leukodystrophies, behavioral disorders, addiction, anxiety, pain, diabetes, renal artery stenosis, interstitial nephritis, glomerulonephritis, polycystic kidney disease, systemic lupus erythematosus, renal tubular acidosis, IgA nephropathy, asthma, emphysema, scleroderma, adult respiratory distress syndrome (ARDS), lymphedema, graft versus host disease (GVHD), pancreatitis, obesity, ulcers, anemia, ataxia-telangiectasia, cancer, trauma, viral infections, bacterial infections, parasitic infections and/or other pathologies and disorders of the like. Also within the scope of the invention is the use of a therapeutic in the manufacture of a medicament for treating or preventing conditions including, e.g., transplantation, neuroprotection, fertility, or regeneration (in vitro and in vivo).

[0017] The therapeutic can be, e.g., a NOVX nucleic acid, a NOVX polypeptide, or a NOVX-specific antibody, or biologically-active derivatives or fragments thereof.

[0018] For example, the compositions of the present invention will have efficacy for treatment of patients suffering from the diseases and disorders disclosed above and/or other pathologies and disorders of the like. The polypeptides can be used as immunogens to produce antibodies specific for the invention, and as vaccines. They can also be used to screen for potential agonist and antagonist compounds. For example, a cDNA encoding NOVX may be useful in gene therapy, and NOVX may be useful when administered to a subject in need thereof.

[0019] The invention further includes a method for screening for a modulator of disorders or syndromes including, e.g., the diseases and disorders disclosed above and/or other pathologies and disorders of the like. The method includes contacting a test compound with a NOVX polypeptide and determining if the test compound binds to said NOVX polypeptide. Binding of the test compound to the NOVX polypeptide indicates the test compound is a modulator of activity, or of latency or predisposition to the aforementioned disorders or syndromes.

[0020] Also within the scope of the invention is a method for screening for a modulator of activity, or of latency or predisposition to disorders or syndromes including, e.g., the diseases and disorders disclosed above and/or other pathologies and disorders of the like by administering a test compound to a test animal at increased risk for the aforementioned disorders or syndromes. The test animal expresses a recombinant polypeptide encoded by a NOVX nucleic acid. Expression or activity of NOVX polypeptide is then measured in the test animal, as is expression or activity of the protein in a control animal which recombinantly-expresses NOVX polypeptide and is not at increased risk for the disorder or syndrome. Next, the expression of NOVX polypeptide in both the test animal and the control animal is compared. A change in the activity of NOVX polypeptide in the test animal relative to the control animal indicates the test compound is a modulator of latency of the disorder or syndrome.

[0021] In yet another aspect, the invention includes a method for determining the presence of or predisposition to a disease associated with altered levels of a NOVX polypeptide, a NOVX nucleic acid, or both, in a subject (e.g., a human subject). The method includes measuring the amount of the NOVX polypeptide in a test sample from the subject and comparing the amount of the polypeptide in the test sample to the amount of the NOVX polypeptide present in a control sample. An alteration in the level of the NOVX polypeptide in the test sample as compared to the control sample indicates the presence of or predisposition to a disease in the subject. Preferably, the predisposition includes, e.g., the diseases and disorders disclosed above and/or other pathologies and disorders of the like. Also, the expression levels of the new polypeptides of the invention can be used in a method to screen for various cancers as well as to determine the stage of cancers.

[0022] In a further aspect, the invention includes a method of treating or preventing a pathological condition associated with a disorder in a mammal by administering to the subject a NOVX polypeptide, a NOVX nucleic acid, or a NOVX-specific antibody to a subject (e.g., a human subject), in an amount sufficient to alleviate or prevent the pathological condition. In preferred embodiments, the disorder, includes, e.g., the diseases and disorders disclosed above and/or other pathologies and disorders of the like.

[0023] In yet another aspect, the invention can be used in a method to identity the cellular receptors and downstream effectors of the invention by any one of a number of techniques commonly employed in the art. These include but are not limited to the two-hybrid system, affinity purification, co-precipitation with antibodies or other specific-interacting molecules.

[0024] NOVX nucleic acids and polypeptides are further useful in the generation of antibodies that bind immuno-specifically to the novel NOVX substances for use in therapeutic or diagnostic methods. These NOVX antibodies may be generated according to methods known in the art, using prediction from hydrophobicity charts, as described in the “Anti-NOVX Antibodies” section below. The disclosed NOVX proteins have multiple hydrophilic regions, each of which can be used as an immunogen. These NOVX proteins can be used in assay systems for functional analysis of various human disorders, which will help in understanding of pathology of the disease and development of new drug targets for various disorders.

[0025] The NOVX nucleic acids and proteins identified here may be useful in potential therapeutic applications implicated in (but not limited to) various pathologies and disorders as indicated below. The potential therapeutic applications for this invention include, but are not limited to: protein therapeutic, small molecule drug target, antibody target (therapeutic, diagnostic, drug targeting/cytotoxic antibody), diagnostic and/or prognostic marker, gene therapy (gene delivery/gene ablation), research tools, tissue regeneration in vivo and in vitro of all tissues and cell types composing (but not limited to) those defined here.

[0026] 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.

[0027] Other features and advantages of the invention will be apparent from the following detailed description and claims.

DETAILED DESCRIPTION OF THE INVENTION

[0028] 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 A provides a summary of the NOVX nucleic acids and their encoded polypeptides.

TABLE A
Sequences and Corresponding SEQ ID Numbers
		SEQ ID
		NO
NOVX	Internal	(nucleic	SEQ ID NO
Assignment	Identification	acid)	(polypeptide)	Homology
NOV1a	CG100570-01	1	2	Leucine Rich Repeat-like Homo sapiens
				proteins
NOV2a	CG100750-01	3	4	Leucine Rich Repeat proteins
NOV3a	CG101201-01	5	6	Adenine Nucleotide Translocator 2
				(ADP/ATP Translocase 2)-like Homo
				sapiens proteins
NOV4a	CG101211-01	7	8	Mitochondrial energy transfer protein
				domain-like Homo sapiens proteins
NOV5a	CG101274-01	9	10	ATRAP-like Homo sapiens proteins
NOV6a	CG101904-01	11	12	Cytosolic phosphoprotein proteins
NOV7a	CG102016-01	13	14	PAX 3A-like Homo sapiens proteins
NOV8a	CG102092-01	15	16	GRP-1-Associated Scaffold Protein
				GRASP proteins
NOV9a	CG102595-01	17	18	NEURABIN 1-like Homo sapiens
				proteins
NOV10a	CG102744-01	19	20	Epidermal fatty acid binding protein-
				like Homo sapiens proteins
NOV11a	CG102801-01	21	22	Septin 6 (KIAA0128)-like Homo
				sapiens proteins
NOV12a	CG102899-01	23	24	RIM2-4C-like Homo sapiens proteins
NOV13a	CG105284-01	25	26	Cell Growth Regulator Falkor-like
				Homo sapiens-
				like proteins
NOV14a	CG105444-01	27	28	Meningioma-Expressed Antigen 6/11
				(MEA6) (MEA11)-like Homo sapiens
				proteins
NOV15a	CG105482-01	29	30	Meningioma-Expressed Antigen 6/11
				(MEA6) (MEA11)-like Homo sapiens
				proteins
NOV16a	CG105617-01	31	32	Liprin alpha 4-like Homo sapiens
				proteins
NOV17a	CG105638-01	33	34	Q9GKW8-like Homo sapiens proteins
NOV18a	CG105617-01	35	36	GTPase Activator Protein-like Homo
				sapiens proteins
NOV19a	CG105778-01	37	38	PEFLIN-like Homo sapiens proteins
NOV20a	CG105796-01	39	40	Neurotransmitter-gated ion-channel-like
				Homo sapiens proteins
NOV21a	CG106002-01	41	42	Carboxyl-Terminal PDZ Ligand of
				Neuronal Nitric Oxide Synthase-like
				Homo sapiens proteins
NOV22a	CG106868-01	43	44	Amyloid Beta A4 Precursor Protein-
				Binding Family B Member 2-like Homo
				sapiens proteins
NOV23a	CG106988-01	45	46	Calreticulin Precursor-like Homo
				sapiens proteins
NOV24a	CG107363-01	47	48	Protein Kinase C Inhibitor-like Homo
				sapiens proteins
NOV24b	CG107363-02	49	50	Protein Kinase C Inhibitor-like Homo
				sapiens proteins
NOV24c	CG107363-03	51	52	Protein Kinase C Inhibitor-like Homo
				sapiens proteins
NOV25a	CG108360-01	53	54	PAX Transcription Activation Domain
				Interacting Protein PTIP-like Homo
				sapiens proteins
NOV26a	CG108762-01	55	56	MAP1 Light Chain 3 Related Protein-
				like Homo sapiens proteins
NOV27a	CG108829-01	57	58	Intacellular signaling protein-like Homo
				sapiens proteins
NOV28a	CG108861-01	59	60	FISH Protein-like Homo sapiens
				proteins
NOV29a	CG109523-01	61	62	profilaggrin-like Homo sapiens proteins
NOV30a	CG109649-01	63	64	Intacellular signaling protein-like Homo
				sapiens proteins
NOV31a	CG110063-01	65	66	VP3 domain-containing protein-like
				Homo sapiens proteins
NOV31b	CG110063-02	67	68	VP3 domain-containing protein-like
				proteins
NOV32a	CG110151-01	69	70	PX19-like Homo sapiens proteins
NOV33a	CG110340-01	71	72	Polyubiquitin-like Homo sapiens
				proteins
NOV34a	CG139264-01	73	74	Pathcalling Protein-like Homo sapiens
				proteins
NOV35a	CG148240-01	75	76	MYND zinc finger (ZnF) domain-
				containing protein-like Homo sapiens
				proteins
NOV36a	CG59975-01	77	78	Q9N061-like Homo sapiens proteins
NOV36b	CG59975-02	79	80	Q9N061-like Homo sapiens proteins
NOV37a	CG89947-01	81	82	Stra8-like Homo sapiens proteins
NOV37b	CG89947-02	83	84	Stra8-like Homo sapiens proteins
NOV38a	CG93366-02	85	86	Membrane Protein Kinase-like Homo
				sapiens proteins
NOV39a	CG97068-02	87	88	Delta 4 3-Oxosteroid 5 Beta Reductase-
				like Homo sapiens proteins

[0029] Table A 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 A 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 A.

[0030] 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.

[0031] Consistent with other known members of the family of proteins, identified in column 5 of Table A, 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.

[0032] 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 A.

[0033] 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.

[0034] Additional utilities for NOVX nucleic acids and polypeptides according to the invention are disclosed herein.

[0035] NOVX Clones

[0036] 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.

[0037] 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.

[0038] 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.

[0039] 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 44; (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 44, 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 44; (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 44, 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).

[0040] 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 44; (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 44, 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 44; (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 44, 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 44, 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.

[0041] 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 44; (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 44, 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 44; 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 44, 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.

[0042] NOVX Nucleic Acids and Polypeptides

[0043] 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.

[0044] 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.

[0045] 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.

[0046] 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.

[0047] 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 44, 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 44, 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.)

[0048] 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, e.g., using an automated DNA synthesizer.

[0049] 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 44, or a complement thereof. Oligonucleotides may be chemically synthesized and may also be used as probes.

[0050] In another embodiment, an isolated nucleic acid molecule of the invention comprises a nucleic acid molecule that is a complement of the nucleotide sequence shown in SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, 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 a, that is complementary to the nucleotide sequence shown SEQ ID NO:2n-1, wherein n is an integer between 1 and 44 is one that is sufficiently complementary to the nucleotide sequence shown SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, that it can hydrogen bond with little or no mismatches to the nucleotide sequence shown SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, thereby forming a stable duplex.

[0051] 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.

[0052] 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.

[0053] 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.

[0054] Derivatives and analogs may be fill 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.

[0055] 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 44, as well as a polypeptide possessing NOVX biological activity. Various biological activities of the NOVX proteins are described below.

[0056] 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.

[0057] 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 44; or an anti-sense strand nucleotide sequence of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44; or of a naturally occurring mutant of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44.

[0058] 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.

[0059] “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 44, 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.

[0060] NOVX Nucleic Acid and Polypeptide Variants

[0061] 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 44, 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 44. 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 44.

[0062] In addition to the human NOVX nucleotide sequences shown in SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, 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.

[0063] 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 44, 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.

[0064] 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 44. 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.

[0065] 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.

[0066] 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 defmed 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 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.

[0067] 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 44, 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).

[0068] 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 44, 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 Protocole in Molecular Biology, John Wiley & Sons, NY, and Kriegler, 1990; Gene Transfer and Expression, a Laboratory Manual, Stockton Press, NY.

[0069] 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 44, 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 50C. 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.

[0070] Conservative Mutations

[0071] 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 44, 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 44. 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.

[0072] 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, wherein n is an integer between 1 and 44, 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 44. 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 44; more preferably at least about 70% homologous SEQ ID NO:2n, wherein n is an integer between 1 and 44; still more preferably at least about 80% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 44; even more preferably at least about 90% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 44; and most preferably at least about 95% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 44.

[0073] 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 44, 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 44, such that one or more amino acid substitutions, additions or deletions are introduced into the encoded protein.

[0074] Mutations can be introduced into SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, by 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 of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44, the encoded protein can be expressed by any recombinant technology known in the art and the activity of the protein can be determined.

[0075] 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.

[0076] 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).

[0077] 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).

[0078] Antisense Nucleic Acids

[0079] 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 44, 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 44, 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 44, are additionally provided.

[0080] 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).

[0081] 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).

[0082] 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-N6-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 subdloned 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).

[0083] 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.

[0084] 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.

[0085] Ribozymes and PNA Moieties

[0086] 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.

[0087] 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 44). 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.

[0088] 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.

[0089] 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.

[0090] 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).

[0091] 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.

[0092] 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. WO 88/09810) 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.

[0093] NOVX Polypeptides

[0094] 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 44. 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 44, while still encoding a protein that maintains its NOVX activities and physiological functions, or a functional fragment thereof.

[0095] 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.

[0096] 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.

[0097] 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.

[0098] 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.

[0099] 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 44) 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.

[0100] 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.

[0101] In an embodiment, the NOVX protein has an amino acid sequence shown SEQ ID NO:2n, wherein n is an integer between 1 and 44. In other embodiments, the NOVX protein is substantially homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 44, and retains the functional activity of the protein of SEQ ID NO:2n, wherein n is an integer between 1 and 44, 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 44, and retains the functional activity of the NOVX proteins of SEQ ID NO:2n, wherein n is an integer between 1 and 44.

[0102] Determining Homology Between Two or More Sequences

[0103] 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”).

[0104] 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 sequence shown in SEQ ID NO:2n-1, wherein n is an integer between 1 and 44.

[0105] 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.

[0106] Chimeric and Fusion Proteins

[0107] The invention also provides NOVX chimeric or fusion proteins. As used herein, an 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 44), 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.

[0108] 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.

[0109] 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.

[0110] 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.

[0111] 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.

[0112] NOVX Agonists and Antagonists

[0113] 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.

[0114] 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.

[0115] Polypeptide Libraries

[0116] 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.

[0117] 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.

[0118] Anti-NOVX Antibodies

[0119] Also included in the invention are antibodies to NOVX proteins, or fragments of NOVX proteins. 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, an antibody molecule 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.

[0120] An isolated NOVX-related protein of the invention may be intended to serve as an antigen, or a portion or fragment thereof, and additionally 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 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.

[0121] In certain embodiments of the invention, at least one epitope encompassed by the antigenic peptide is a region of NOVX-related protein that is located on the surface of the protein, e.g., a hydrophilic region. A hydrophobicity analysis of the human NOVX-related protein sequence will indicate which regions of a NOVX-related protein 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 of which is incorporated herein by reference in its 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.

[0122] 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.

[0123] 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 and Lane, 1988, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., incorporated herein by reference). Some of these antibodies are discussed below.

[0124] Polyclonal Antibodies

[0125] 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).

[0126] 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).

[0127] Monoclonal Antibodies

[0128] 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.

[0129] 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.

[0130] 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.

[0131] 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 Antobody Production Techniques and Applications, Marcel Dekker, Inc., New York, (1987) pp. 51-63).

[0132] 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). Preferably, antibodies having a high degree of specificity and a high binding affinity for the target antigen are isolated.

[0133] After the desired hybridoma cells are identified, the clones can be subcloned by limiting dilution procedures and grown by standard methods. 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.

[0134] 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.

[0135] 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.

[0136] Humanized Antibodies

[0137] 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)).

[0138] Human Antibodies

[0139] Fully human antibodies relate to antibody molecules in which essentially the entire sequences 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).

[0140] 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 14, 845-51 (1996)); Neuberger (Nature Biotechnology 14, 826 (1996)); and Lonberg and Huszar (Intern. Rev. Immunol. 13 65-93 (1995)).

[0141] 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.

[0142] 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.

[0143] 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.

[0144] 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.

[0145] Fab Fragments and Single Chain Antibodies

[0146] 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.

[0147] Bispecific Antibodies

[0148] 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.

[0149] 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., 1991 EMBO J., 10:3655-3659.

[0150] 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 Enzymnology, 121:210 (1986).

[0151] 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.

[0152] 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.

[0153] 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.

[0154] 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, Gruberetal., J. Immunol. 152:5368 (1994).

[0155] Antibodies with more than two valencies are contemplated. For example, trispecific antibodies can be prepared. Tutt et al., J. Immunol. 147:60 (1991).

[0156] 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).

[0157] Heteroconjugate Antibodies

[0158] 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.

[0159] Effector Function Engineering

[0160] 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).

[0161] Immunoconjugates

[0162] 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).

[0163] 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 186Re.

[0164] 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.

[0165] 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.

[0166] In one embodiment, methods for the screening of antibodies that possess the desired specificity include, but are not limited to, enzyme-linked immunosorbent assay (ELISA) and other immunologically-mediated techniques known within the art. In a specific embodiment, selection of antibodies that are specific to a particular domain of an NOVX protein is facilitated by generation of hybridomas that bind to the fragment of an NOVX protein possessing such a domain. Thus, antibodies that are specific for a desired domain within an NOVX protein, or derivatives, fragments, analogs or homologs thereof, are also provided herein.

[0167] Anti-NOVX antibodies may be used in methods known within the art relating to the localization and/or quantitation of an NOVX protein (e.g., for use in measuring levels of the NOVX protein within appropriate physiological samples, for use in diagnostic methods, for use in imaging the protein, and the like). In a given embodiment, antibodies for NOVX proteins, or derivatives, fragments, analogs or homologs thereof, that contain the antibody derived binding domain, are utilized as pharmacologically-active compounds (hereinafter “Therapeutics”).

[0168] An anti-NOVX antibody (e.g., monoclonal antibody) can be used to isolate an NOVX polypeptide by standard techniques, such as affinity chromatography or immunoprecipitation. An anti-NOVX antibody can facilitate the purification of natural NOVX polypeptide from cells and of recombinantly-produced NOVX polypeptide expressed in host cells. Moreover, an anti-NOVX antibody can be used to detect NOVX protein (e.g., in a cellular lysate or cell supernatant) in order to evaluate the abundance and pattern of expression of the NOVX protein. Anti-NOVX antibodies 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 streptavidinibiotin 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.

[0169] NOVX Recombinant Expression Vectors and Host Cells

[0170] 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.

[0171] 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 transcriptionptranslation system or in a host cell when the vector is introduced into the host cell).

[0172] 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.).

[0173] 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.

[0174] 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.

[0175] Examples of suitable inducible non-fusion E. coli expression vectors include pTrc (Amrann et al., (1 988) 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).

[0176] 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.

[0177] In another embodiment, the NOVX expression vector is a yeast expression vector. Examples of vectors for expression in yeast Saccharomyces cerivisae include pYepSec1 (Baldari, et al., 1987. EMBO J. 6:229-234), pMFa (Kuijan 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.).

[0178] 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).

[0179] 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.

[0180] 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 (Baneiji, 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).

[0181] 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.

[0182] 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.

[0183] 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.

[0184] 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.

[0185] 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).

[0186] 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.

[0187] Transgenic NOVX Animals

[0188] 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.

[0189] 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 44, 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.

[0190] 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 44), 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 44, 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).

[0191] 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.

[0192] 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: Teratocarcinomas 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.

[0193] 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.

[0194] 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.

[0195] Pharmaceutical Compositions

[0196] 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.

[0197] 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, intradermnal, 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.

[0198] 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.

[0199] 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.

[0200] 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.

[0201] 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.

[0202] 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.

[0203] 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.

[0204] 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.

[0205] 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.

[0206] 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, or can 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.

[0207] The pharmaceutical compositions can be included in a container, pack, or dispenser together with instructions for administration.

[0208] Screening and Detection Methods

[0209] 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.

[0210] The invention farther pertains to novel agents identified by the screening assays described herein and uses thereof for treatments as described, supra.

[0211] Screening Assays

[0212] 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.

[0213] 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. Anticaticer Drug Design 12: 145.

[0214] 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.

[0215] 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.

[0216] Libraries of compounds may be presented in solution (e.g., Houghten, 1992. Biotechniques 13: 412-421), or onbeads (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. Patent 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.).

[0217] 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.

[0218] 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.

[0219] 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.

[0220] 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.

[0221] 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.

[0222] 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.

[0223] 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, Triton® X-114, Thesit®, decanoyl-N-methylglucamide, Tritone® X-100, 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).

[0224] 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.

[0225] 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.

[0226] 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 MnRNA 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 (i.e., 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.

[0227] 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.

[0228] 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., GAL-4). 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.

[0229] 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.

[0230] The invention further pertains to novel agents identified by the aforementioned screening assays and uses thereof for treatments as described herein.

[0231] Detection Assays

[0232] 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.

[0233] Chromosome Mapping

[0234] 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 44, 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.

[0235] 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.

[0236] 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 flull 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.

[0237] 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.

[0238] Fluorescence in situ hybridization (FISH) of a DNA sequence to a metaphase chromosomal 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).

[0239] 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.

[0240] 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, Mendellan 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.

[0241] 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.

[0242] Tissue Typing

[0243] 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).

[0244] 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.

[0245] 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).

[0246] 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 44, are used, a more appropriate number of primers for positive individual identification would be 500-2,000.

[0247] Predictive Medicine

[0248] 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, 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.

[0249] 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.)

[0250] 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.

[0251] These and other agents are described in further detail in the following sections.

[0252] Diagnostic Assays

[0253] 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 44, 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.

[0254] 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.

[0255] 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.

[0256] 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.

[0257] 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.

[0258] Prognostic Assays

[0259] 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.

[0260] 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).

[0261] 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.

[0262] 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.

[0263] 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.

[0264] 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.

[0265] 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.

[0266] 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).

[0267] 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.

[0268] 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.

[0269] 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.

[0270] 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.

[0271] 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.

[0272] 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.

[0273] 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.

[0274] 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.

[0275] Pharmacogenomics

[0276] 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) various disorders including: 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 as well as diseases disorders associated with homologs of NOVX proteins summarized in Table A. 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.

[0277] 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.

[0278] 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 P450 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 CYP2C19 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.

[0279] 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.

[0280] Monitoring of Effects During Clinical Trials

[0281] 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. 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.

[0282] 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.

[0283] 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, ie., to decrease the effectiveness of the agent.

[0284] Methods of Treatment

[0285] 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, adrenoleukodystrophy, congenital adrenal hyperplasia, prostate cancer, neoplasm; adenocarcinoma, lymphoma, uterus cancer, 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. Conditions also include transplantation and fertility.

[0286] These methods of treatment will be discussed more fully, below.

[0287] Disease and Disorders

[0288] 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.

[0289] 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 (i.e., 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.

[0290] 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).

[0291] Prophylactic Methods

[0292] 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.

[0293] Therapeutic Methods

[0294] 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.

[0295] 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).

[0296] Determination of the Biological Effect of the Therapeutic

[0297] 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.

[0298] 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.

[0299] Prophylactic and Therapeutic Uses of the Compositions of the Invention

[0300] 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.

[0301] 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.

[0302] 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.

[0303] The invention will be further described in the following examples, which do not limit the scope of the invention described in the claims.

EXAMPLES

Example A

[0304] NOVX Clone Information

Example 1

[0305] The NOV1 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 1A.

TABLE 1A
NOV1 Sequence Analysis
                 SEQ ID NO:1          3504 bp
NOV1a,           GCACAGGGATTCCCAGGGCATCTACCACCACGCAGCTGGAGCAGGGCTGAGCCCAGGA
CG100570-01      GCATGGAGATGGACGCCCCCAGGCCCCCCAGTCTTGCTGTCCCTGGAGCAGCATCGAG
DNA Sequence     GCCCGGGAGGAGGGACAGTGTCCAGGATGAAAGCCACGTTTCGTCTGAATGGGGCCTG
                 AGCAGGGATGCCAGATCAGATACAGGACACTTGGTCAAATGTGAATTTCAAATAATCC
                 ATTTCTTTGCCCCGCTCGGGTCCCGTGGTTCTCAACTCTGGTTAGAACCACCGGAGGA
                 GCTTAAACTAGATCCACGTGGGGGCCCTTGCCAGACCAATCAAATCTCTGGGTGGCTG
                 CTGGATGGGGGGCACGGCAGGCAGCAGGTTCAGGCCCTCTCTTCACAGCTCCTGGAGG
                 TGATCCCCGACTCCATGAGGAAGCAAGAGGTGCGGACGGGCAGGGAGGCCGGCCAGGG
                 CCACGGTACGGGCTCCCCAGCCGAGCAGGTGAAAGCCCTCATGGATCTGCTGGCTGGG
                 AAGGGCAGTCAAGGCTCCCAGGCCCCGCAGGCCCTGGATAGGACACCGGATGCCCCGC
                 TGAGGATACAGAGGCACCGCAAGGCCCTGCTGAGCAAGGTGGGAGGTGGCCCGGAGCT
                 GGGCGGACCCTGGCACAGGCTGGCCTCCCTCCTGCTGGTGGAGGGCCTGACGGACCTG
                 CAGCTGAGGGAACACGACTTCACACAGGTGGAGGCCACCCGCGGGGGCGGGCACCCCG
                 CCAGGACCGTCGCCCTGGACCGGCTCTTCCTGCCTCTCTCCCGGGTGTCTGTCCCACC
                 CCGGGTCTCCATCACTATCGGGGTGGCCGGCATGGGCAAGACCACCCTGGTGAGGCAC
                 TTCGTCCGCCTCTGGGCCCATGGGCAGGTCGGCAAGGACTTCTCGCTGGTGCTGCCTC
                 TGACCTTCCGGGATCTCAACACCCACGAGAAGCTGTGTGCCGACCGACTCATCTGCTC
                 GGTCTTCCCGCACGTCGGGGAGCCCAGCCTGGCGGTGGCAGTCCCAGCCAGGGCCCTC
                 CTGATCCTGGACGGCTTGGATGAGTGCAGGACGCCTCTGGACTTCTCCAACACCGTGG
                 CCTGCACGGACCCAAAGAAGGAGATCCCGGTGGACCACCTGATCACCAACATCATCCG
                 TGGCAACCTCTTTCCGGAAGTTTCCATCTGGATCACCTCCCGTCCCAGTGCATCTGGC
                 CAGATCCCAGGGGGCCTGGTGGACCGGATGACGGAGATCCGGGGCTTTAACGAGGAGG
                 AGATCAAGGTGTGTTTGGAGCAGATGTTCCCCGAGGACCAGGCCCTTCTGGGCTGGAT
                 TGCAGGCTCACGGGGATGGCGCTAGGCCACCTGTGGCGCAGCAGGACGGGGCCCCAGG
                 ATGCAGAGCTGTGGCCCCCGAGGACCCTGTGCGAGCTCTACTCATGGTACTTTAGGAT
                 GGCCCTCAGCGGGGAGGGGCAGGAGAAGGGCAAGGCAAGCCCTCGCATCGAGCAGGTG
                 GCCCATGGTGGCCGCAAGATGGTGGGGACATTGGGCCGTCTGGCCTTCCATGGGCTGC
                 TCTGCTCCAGGGCGCCCCGTGCAGCTGCTTCCTGCAGAGAGAGGAGACGTTGGCATCG
                 TCAGTGGCCTACTGCTTCACCCACCTGTCCCTGCAGGAGTTTGTGGCAGCCGCGTATT
                 ACTATGGCGCATCCAGGAGGGCCATCTTCGACCTCTTCACTGAGAGCGGCGTATCCTG
                 GCCCAGGCTGGGCTTCCTCACGCATTTCAGGAGCGCAGCCCAGCGGGCCATGCAGGCA
                 GAGGACGGGAGGCTGGACGTGTTCCTGCGCTTCCTCTCCGGCCTCTTGTCTCCGAGGG
                 TCAATGCCCTCCTGGCCGGCTCCCTGCTGGCCCAAGGCGAGCACCAGGCCTACCGGAC
                 CCAGGTGGCTGAGCTCCTGCAGGGCTGCCTGCGCCCCGATGCCGCAGTCTGTGCACGG
                 GCCATCAACGTGTTGCACTGCCTGCATGAGCTGCAGCACACCGAGCTGGCCCGCAGCG
                 TGGAGGAGGCCATGGAGAGCGGGGCCCTGGCCAGGCTGACTGGTCCCGCGCACCGCGC
                 TGCCCTGGCCTACCTCCTGCAGGTGTCCGACGCCTGTGCCCAGGAGGCCAACCTGTCC
                 CTGAGCCTCAGCCAGGGCGTCCTTCAGAGCCTGCTGCCCCAGCTGCTCTACTGCCGGA
                 AGCTCAGGAGGCTGGACACCAACCAGTTCCAGGACCCCGTGATGGAGCTGCTGGGCAG
                 CGTGCTGAGTGGGAAGGACTGTCGCATTCAGAAGATCAGCTTGGCGGAGAACCAGATC
                 AGTAACAAAGGGGCCAAAGCTCTGGCCAGATCCCTCTTGGTCAACAGAAGTCTGACCT
                 CTCTGAGCCTCCGCGGTAACTCCATTGGACCACAAGGGGCCAAGGCGCTGGCAGACGC
                 TTTGAAGATCAACCGCACCCTGACCTCCCTGAGCCTCCAGGGCAACACCGTTAGGGAT
                 GATGGTGCCAGGTCCATGGCTGAGGCCTTGGCCTCCAACCGGACCCTCTCCATGCTGC
                 AGTTCTCCAGTAATAGTATTGGTGATGGAGGTGCCAAGGCCCTGGCTGAGGCCCTGAA
                 GGTGAACCAGGGCCTGGAGAGCCTGAGCCTGCAGAGCAATTCCATCAGTGACGCAGGA
                 GTGGCAGCACTGATGGGGGCCCTCTGCACCAACCAGACCCTCCTCAGCCTCAGCCTTC
                 GAGAAAACTCCATCAGTCCCGAGGGAGCCCAGGCCATCGCTCATGCCCTCTGCGCCAA
                 CAGCACCCTGAAGAACCTGGAGTACGTGGTGGGGGCCTGTGACTCCACAGGCTGTTCA
                 TGCCATGACCACACCCACACCGAGCCTGGGCTGACGGGCACCCTCGCCACGAGCCTGA
                 CAGCCAACCTCCTCCACGACCAGGGTGCCCGGGCCATCGCAGTGGCAGTGAGAGAAAA
                 CCGCACCCTCACCTCCCTTCTGCAGTGGAACTTCATCCAGGCCGGCGCTGCCCAGGCC
                 CTGGGACAAGCACTACAGCTCAACAGGAGCCTCACCAGCTTATTACAGGAGAACGCCA
                 TCGGGGATGACGGAGCGTGTGCGGTGGCCCGTGCACTGAAGGTCAACACAGCCCTCAC
                 TGCTCTCCTCCAGGTGGCCTCAATTGGTGCTTCAGGCGCCCAGGTGCTAGGGGAAGCC
                 TTGGCTGTGAACAGAACCTTGGAGATTCTCGAGTTAAGAGGAAATGCCATTGGGGTGG
                 CTGGAGCCAAAGCCCTGGCAAATGCTCTGAAGGTAAACTCAAGTCTCCGGAGACTCAA
                 GTAAGTGGCTGGAGGGACCTACCTGCATCCTGGAGCAGCAGAGTTCTCTGCTGGGTCC
                 TCCCTGATGGAATAAAATGCTCCT
                 ORF Start: ATG at 61 ORF Stop: TAA at 3424
                 SEQ ID NO:2          1121 aa MW at 120708.7 kD
NOV1a,           MEMDAPRPPSLAVPGAASRPGRRDSVQDESHVSSEWGLSRDARSDTGHLVKCEFQIIH
CG100570-01      FFAPLGSRGSQLWLEPPEELKLDPRGGPCQTNQISGWLLDGGHGRQQVQALSSQLLEV
Protein Sequence IPDSMRKQEVRTGREAGQGHGTGSPAEQVKALMDLLAGKGSQGSQAPQALDRTPDAPL
                 RIQRHRKALLSKVGGGPELGGPWHRLASLLLVEGLTDLQLREHDFTQVEATRGGGHPA
                 RTVALDRLFLPLSRVSVPPRVSITIGVAGMGKTTLVRHFVRLWAHGQVGKDFSLVLPL
                 TFRDLNTHEKLCADRLICSVFPHVGEPSLAVAVPARALLILDGLDECRTPLDFSNTVA
                 CTDPKKEIPVDHLITNIIRGNLFPEVSIWITSRPSASGQIPGGLVDRMTEIRGFNEEE
                 IKVCLEQMFPEDQALLGWMLSQVQADRALYLMCTVPAFCRLTGMALGHLWRSRTGPQD
                 AELWPPRTLCELYSWYFRMALSGEGQEKGKASPRIEQVAHGGRKMVGTLGRLAFHGLL
                 KKKYVFYEQDMKAFGVDLALLQGAPCSCFLQREETLASSVAYCFTHLSLQEFVAAAYY
                 YGASRRAIFDLFTESGVSWPRLGFLTHFRSAAQRAMQAEDGRLDVFLRFLSGLLSPRV
                 NALLAGSLLAQGEHQAYRTQVAELLQGCLRPDAAVCARAINVLHCLHELQHTELARSV
                 EEAMESGALARLTGPAHRAALAYLLQVSDACAQEANLSLSLSQGVLQSLLPQLLYCRK
                 LRRLDTNQFQDPVMELLGSVLSGKDCRIQKISLAENQISNKGAKALARSLLVNRSLTS
                 LSLRGNSIGPQGAKALADALKINRTLTSLSLQGNTVRDDGARSMAEALASNRTLSMLQ
                 FSSNSIGDGGAKALAEALKVNQGLESLSLQSNSISDAGVAALMGALCTNQTLLSLSLR
                 ENSISPEGAQAIAHALCANSTLKNLEYVVGACDSTGCSCHDHTHTEPGLTGTLATSLT
                 ANLLHDQGARAIAVAVRENRTLTSLLQWNFIQAGAAQALGQALQLNRSLTSLLQENAI
                 GDDGACAVARALKVNTALTALLQVASIGASGAQVLGEALAVNRTLEILELRGNAIGVA
                 GAKALANALKVNSSLRRLK

[0306] Further analysis of the NOV1a protein yielded the following properties shown in Table 1B.

TABLE 1B
Protein Sequence Properties NOV1a
analysis: located in nucleus; 0.2221 probability located
          in lysosome (lumen); 0.1000 probability
          located in mitochondrial matrix space
SignalP   No Known Signal Sequence Predicted
analysis:

[0307] 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.

TABLE 1C
Geneseq Results for NOV1a
		NOV1a	Identifies/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAG79119	Amino acid sequence of	234 . . . 965	216/780 (27%)	2e−51
	inflammatory bowel disease 1	276 . . . 1034	343/780 (43%)
	(IBD1) protein - Homo sapiens,
	1041 aa. [FR2806739-A1, 28-SEP-2001]
AAM01379	Peptide #61 encoded by probe for	388 . . . 476	89/89 (100%)	9e−48
	measuring human breast gene	1 . . . 89	89/89 (100%)
	expression - Homo sapiens, 89 aa.
	[WO200157270-A2, 09-AUG-2001]
AAM26026	Peptide #63 encoded by probe for	388 . . . 476	89/89 (100%)	9e−48
	measuring placental gene	1 . . . 89	89/89 (100%)
	expression - Homo sapiens, 89 aa.
	[WO200157272-A2, 09-AUG-2001]
AAM13629	Peptide #63 encoded by probe for	388 . . . 476	89/89 (100%)	9e−48
	measuring cervical gene expression -	1 . . . 89	89/89 (100%)
	Homo sapiens, 89 aa.
	[WO200157278-A2, 09-AUG-2001]
AAM65767	Human bone marrow expressed	388 . . . 476	89/89 (100%)	9e−48
	probe encoded protein SEQ ID NO:	1 . . . 89	89/89 (100%)
	26073 - Homo sapiens, 89 aa.
	[WO200157276-A2, 09-AUG-2001]

[0308] In a BLAST search of public sequence datbases, the NOV1a protein was found to have homology to the proteins shown in the BLASTP data in Table 1D.

TABLE 1D
Public BLASTP Results for NOV1a
		NOV1a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
BAB84935	FLJ00180 PROTEIN - Homo	680 . . . 1120	405/472 (85%)	0.0
	sapiens (Human), 499 aa	1 . . . 441	407/472 (85%)
	(fragment).
AAM22459	CARD15-LIKE PROTEIN - Homo	815 . . . 1038	191/253 (75%)	9e−88
	sapiens (Human), 223 aa	1 . . . 223	192/253 (75%)
	(fragment).
AAM22460	CARD15-LIKE PROTEIN - Homo	815 . . . 1011	148/225 (65%)	6e−64
	sapiens (Human), 195 aa	1 . . . 195	155/225 (68%)
	(fragment).
CAD10212	SEQUENCE 1 FROM PATENT	234 . . . 965	216/780 (27%)	6e−51
	WO0172822 - Homo sapiens	276 . . . 1034	343/780 (43%)
	(Human), 1041 aa.
Q9HC29	Caspase recruitment domain	234 . . . 965	216/780 (27%)	6e−51
	protein 15 (Nod2 protein)	275 . . . 1033	343/780 (43%)
	(Inflammatory bowel disease
	protein 1) - Homo sapiens
	(Human), 1040 aa.

[0309] PFam analysis predicts that the NOV1a protein contains the domains shown in the Table 1E.

TABLE 1E
Domain Analysis of NOV1a
Pfam Domain	NOV1a Match Region	Identities/	Expect
		Similarities	Value
		for the Matched
		Region

Example 2

[0310] The NOV2 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 2A.

TABLE 2A
NOV2 Sequence Analysis
                 SEQ ID NO:3         2049 bp
NOV2a,           CTAGACCACAGAAGAAAATACAGAGAGAACATGAAGGCTGAACTACTGGAGACATGGG
CG100750-01      ACAACATCAGTTGGCCTAAAGACCACGTATATATCCGTAATACATCAAAGGACGAACA
DNA Sequence     TGAGGAACTGCAGCGCCTACTGGATCCTAATAGGACTAGAGCCCAGGCCCAGACGATA
                 GTCTTGGTGGGGAGGGCAGGGGTTGGGAAGACCACCTTGGCAATGCAGGCTATGCTGC
                 ACTGGGCAAATGGAGTTCTCTTTCAGCAAAGGTTCTCCTATGTTTTCTATCTCAGCTG
                 CCATAAAATAAGGTACATGAAGGAAACTACCTTTGCTGAATTGATTTCTTTGGATTGG
                 CCCGATTTTGATGCCCCCATTGAAGAGTTCATGTCTCAACCAGAGAAGCTCCTGTTTA
                 TTATTGATGGCTTTGAGGAAATAATCATATCTGAGTCACGCTCTGAGAGCTTGGATGA
                 TGGCTCGCCATGTACAGACTGGTACCAGGAGCTCCCAGTGACCAAAATCCTACACAGC
                 TTGTTGAAGAAAGAATTGGTTCCCCTGGCTACCTTACTGATCACGATCAAGACCTGGT
                 TTGTGAGAGATCTTAAGGCCTCATTAGTGAATCCATGCTTTGTACAAATTACAGGGTT
                 CACAGGGGACGACCTACGGGTATATTTCATGAGACACTTTGATGACTCAAGTGAAGTT
                 TCTCCAGTCAATCACTCAGACTACCACCAGTCTGTATGCCTATTTTTTCTCCAACTTG
                 TTCTCCACAGCAGAGGTAGATTTGGCAGATGACAGCTGGCCAGGACAATGGAGGGCCC
                 TCTGCAGTCTGGCCATAGAAGGGCTGTGGTCTATGAACTTCACGTTTAACAAAGAAGA
                 CACTGAGATCGAGGGCCTGGAAGTGCCTTTCATTGATTCTCTCTACGAGTTCAATATT
                 CTTCAAAAGATCAATGACTGTGGGGGTTGCACTACTTTCACCCACCTAAGTTTCCAGG
                 AGTTTTTTGCAGCCATGTCCTTTGTGCTAGAGGAACCTAGAGAATTCCCTCCCCATTC
                 CACAAAGCCACAAGAGATGAAGATGTTACTGCAACACGTCTTGCTTGACAAAGAAGCC
                 TACTGGACTCCAGTGGTTCTGTTCTTCTTTGGTCTTTTAAATAAAAACATAGCAAGAG
                 AACTGGAAGATACTTTGCATTGTAAAATATCTCCCAGGGTAATGGAGGAATTATTAAA
                 CTTTTTCACTGCCTACACGAGTCCCAGGAGGAAGACTTCACAAAGAAGATGTTGGGTC
                 GTATCTTTGAAGTTGACCTTAATATTTTGGAGGACGAAGAACTCCAAGCTTCTTCATT
                 TTGCCTAAAGCACTGTAAAAGGTTAAATAAGCTAAGGCTTTCTGTTAGCAGTCACATC
                 CTTGAAAGGGACTTGGAAATTCTGGAGACAAGCAAGTTTGATTCCAGGATGCACGCAT
                 GGAACAGCATTTGCTCTACGTTGGTCACAAATGAGAATCTGCATGAGCTAGACCTGAG
                 TAACAGCAAACTTCATGCTTCCTCTGTGAAGGGTCTCTGTCTTGCACTGAAAAATCCA
                 AGATGCAAAGTCCAGAAACTGACGCTCAGGTGCAAATCGGTAACTCCTGAGTGGGTTC
                 TGCAGGACCTCATTATTGCCCTTCAGGGTAACAGCAAGCTGACCCATCTGAACTTCAG
                 CTCTAACAAGCTGGGAATGACTGTCCCCCTGATTCTTAAAGCTTTGAGACACTCAGCT
                 TGCAACCTCAAGTATCTGTGGTAAGTCTTTGGCTCCCTAGATCTGTCAAGGGGGGTTG
                 CAAGACCACCAGTAGCTTCCACGATCCACTGGGAGGGCTGACAGCACTCAGCCTTGTA
                 GCAAAAGGAGACAGAGAAG
                 ORF Start ATG at 31 ORF Stop: TAA at 1936
                 SEQ ID NO:4         635 aa MW at 73523.9 kD
NOV2a,           MKAELLETWDNISWPKDHVYIRNTSKDEHEELQRLLDPNRTRAQAQTIVLVGRAGVGK
CG100750-01      TTLAMQAMLHWANGVLFQQRFSYVFYLSCHKIRYMKETTFAELISLDWPDFDAPIEEF
Protein Sequence MSQPEKLLFIIDGFEEIIISESRSESLDDGSPCTDWYQELPVTKILHSLLKKELVPLA
                 TLLITIKTWFVRDLKASLVNPCFVQITGFTGDDLRVYFMRHFDDSSEVEKILQQLRKN
                 ETLFHSCSAPMVCWTVCSCLKQPKVRYYDLQSITQTTTSLYAYFFSNLFSTAEVDLAD
                 DSWPGQWRALCSLAIEGLWSMNFTFNKEDTEIEGLEVPFIDSLYEFNILQKINDCGGC
                 TTFTHLSFQEFFAAMSFVLEEPREFPPHSTKPQEMKMLLQHVLLDKEAYWTPVVLFFF
                 GLLNKNTARELEDTLHCKISPRVMEELLKWGEELGKAESASLQFHILRLFHCLHESQE
                 EDFTKKMLGRIFEVDLNILEDEELQASSFCLKHCKRLNKLRLSVSSHTLERDLEILET
                 SKFDSRMHAWNSICSTLVTNENLHELDLSNSKLHASSVKGLCLALKNPRCKVQKLTLR
                 CKSVTPEWVLQDLIIALQGNSKLTHLNFSSNKLGMTVPLILKALRHSACNLKYLW

[0311] Further analysis of the NOV2a protein yielded the following properties shown in Table 2B.

TABLE 2B
Protein Sequence Properties NOV2a
PSort     0.5789 probability located in microbody (peroxisome);
analysis: 0.1000 probability located in mitochondrial matrix space;
          0.1000 probability located in lysosome (lumen);
          0.0000 probability located in endoplasmic reticulum
          (membrane)
SignalP   No Known Signal Sequence Predicted
analysis:

[0312] 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 2C.

TABLE 2C
Geneseq Results for NOV2a
		NOV2a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAM50327	Human nucleotide binding site	1 . . . 521	521/521 (100%)	0.0
	protein NBS-4 - Homo sapiens,	1 . . . 521	521/521 (100%)
	521 aa. [WO200183753-A2, 08-NOV-2001]
AAE07514	Human PYRIN-1 protein - Homo	31 . . . 635	213/642 (33%)	9e−97
	sapiens, 1034 aa. [WO200161005-	202 . . . 831	345/642 (53%)
	A2, 23-AUG-2001]
AAM50328	Human nucleotide binding site	9 . . . 634	206/628 (32%)	3e−92
	protein NBS-5 - Homo sapiens,	4 . . . 621	335/628 (52%)
	858 aa. [WO200183753-A2, 08-NOV-2001]
ABG28379	Novel human diagnostic protein	1 . . . 634	207/647 (31%)	4e−90
	#28370 - Homo sapiens, 877 aa.	191 . . . 815	333/647 (50%)
	[WO200175067-A2, 11-OCT-2001]
AAE07513	Human nucleotide binding site 1	1 . . . 634	207/647 (31%)	4e−90
	(NBS-1) protein - Homo sapiens,	136 . . . 760	333/647 (50%)
	1033 aa. [WO200161005-A2, 23-AUG-2001]

[0313] In a BLAST search of public sequence datbases, the NOV2a protein was found to have homology to the proteins shown in the BLASTP data in Table 2D.

TABLE 2D
Public BLASTP Results for NOV2a
		NOV2a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
CAD19385	SEQUENCE 5 FROM PATENT	1 . . . 521	521/521 (100%)	0.0
	WO0183753 - Homo sapiens	1 . . . 521	521/521 (100%)
	(Human), 521 aa.
Q96P20	Cold autoinflammatory syndrome 1	31 . . . 635	213/642 (33%)	2e−96
	protein (Cryopyrin) (NACHT-,	202 . . . 831	345/642 (53%)
	LRR- and PYD-containing protein
	3) (PYRIN-containing APAF1-like
	protein 1) (Angiotensin/vasopressin
	receptor AII/AVP-like) - Homo
	sapiens (Human), 1034 aa.
AAL78632	NALP3 LONG ISOFORM - Homo	31 . . . 635	212/642 (33%)	4e−96
	sapiens (Human), 1036 aa.	204 . . . 833	345/642 (53%)
Q96MN2	CDNA FLJ32126 FIS, CLONE	2 . . . 634	208/635 (32%)	1e−92
	PEBLM2000112, WEAKLY	29 . . . 653	338/635 (52%)
	SIMILAR TO Homo sapiens
	NUCLEOTIDE-BINDING SITE
	PROTEIN 1 MRNA - Homo sapiens
	(Human), 919 aa.
Q96MN2	NACHT-, LRR- and PYD-	2 . . . 634	208/635 (32%)	1e−92
	containing protein 4 (PAAD and	104 . . . 728	338/635 (52%)
	NACHT-containing protein 2)
	(PYRIN-containing APAF1-like
	protein 4) (Ribonuclease inhibitor 2) -
	Homo sapiens (Human), 994 aa.

[0314] PFam analysis predicts that the NOV2a protein contains the domains shown in the Table 2E.

TABLE 2E
Domain Analysis of NOV2a
		Identities/
Pfam		Similarities	Expect
Domain	NOV2a Match Region	for the Matched Region	Value
NB-ARC	32 . . . 65	13/34 (38%)	0.0058
		27/34 (79%)

Example 3

[0315] The NOV3 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 3A.

TABLE 3A
NOV3 Sequence Analysis
                 SEQ ID NO:5          925 bp
NOV3a,           CCGCCTGCCTCCTCTTCCTTTCAACATGACAGATGCCGCTGTGTCCTTGGCCAAGGAC
CG101201-01      TTCCTGGCAGGTGGAGTGACCGCGGCCATCTCCAAGATGGCGGTGGCACCCACGGAGG
DNA Sequence     GGGTCAAGCTGCTGCTGCAGGTGCAGAGTGCCAGCAAGCAGATCACCGCAGATAAGCA
                 ATACACGGGCGTTGTAGACTGCATGGTCCGCATTCCCAAGGAGCAGGGAGCAGGAGTC
                 CTGTCCCTCTGGCACGGTAACCTGGCCAATGTCATCAGATACTTCCCTACCCACGCTC
                 TCAACTTTGCCTTCAAAGATAAAAACAAGCAGATCTTCCCGGGGGGTGTGGACAAGAG
                 GATCCAGTTTTGGCACAAGTTTGCAGGGAGTCTGGCATCAGGTGGTGCCCCTGGGGCC
                 ACATCCTTATGTTTTGTATACCCTCTTGATTTTGACCGTACCCATCTAGCAGCTGATG
                 TGGGTAAAGCTGGAGCTGAAAGGGAATTCCAAGGCCTTGGTGACCGCCTGGTTAAGAT
                 CTACAAATCTGATGGGATTAAAGGCCTGTACCAAGGCTCTAACAGCTCTGTGCAGGGT
                 ATTATCATCTACCGAGCTGCCTGCTTCGGTGTCTATGACACTGCAAGGAGAATGCTTC
                 CAGATTCCAGGAACACTCACGTCATCAGCCGTATGATCGCGCAGTCCGTCACTGCCGT
                 TGCTGGGTTGACTTCCTATCCATTTGACGCTGTTCGCCACGGAATGATGATGCAGTCA
                 GGGCAGGGTGCAGCTGACATCATGTACACAGGCAGGCTTCACTGCTGGAGGAAGATTG
                 CTCCTGATGAAGGAGGCAGAGCTTTTTTCAAGGGTGCATGGTCCAATGTTCTCAGAGG
                 CATGGGTGGTGCGTTTGTGCTTGTCTTGTATGATGAAATCAGAAAGTACACATAA
                 ORF Start: ATG at 26 ORF Stop: TAA at 923
                 SEQ ID NO:6          299 aa MW at 32484.2 kD
NOV3a,           MTDAAVSLAKDFLAGGVTAAISKMAVAPTEGVKLLLQVQSASKQITADKQYTGVVDCM
CG101201-01      VRIPKEQGAGVLSLWHGNLANVIRYFPTHALNFAFKDKNKQIFPGGVDKRIQFWHKFA
Protein Sequence GSLASGGAPGATSLCFVYPLDFDRTHLAADVGKAGAEREFQGLGDRLVKIYKSDGIKG
                 LYQGSNRSVQGIIIYRAACFGVYDTARRMLPDSRNTHVISRMIAQSVTAVAGLTSYPF
                 DAVRHGMMMQSGQGAADIMYTGRLHCWRKIAPDEGGRAFFKGAWSNVLRGMGGAFVLV
                 LYDEIRKYT

[0316] Further analysis of the NOV3a protein yielded the following properties shown in Table 3B.

TABLE 3B
Protein Sequence Properties NOV3a
PSort     0.6400 probability located in microbody (peroxisome);
analysis: 0.3600 probability located in mitochondrial matrix space;
          0.3088 probability located in lysosome (lumen);
          0.3000 probability located in mitochondrial
          intermembrane space
SignalP   No Known Signal Sequence Predicted
analysis:

[0317] 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.

TABLE 3C
Geneseq Results for NOV3a
		NOV3a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAU10379	Human adenine nucleotide	1 . . . 299	249/300 (83%)	e−137
	translocator 2 (ANT2) - Homo	1 . . . 298	262/300 (87%)
	sapiens, 298 aa. [WO200185944-
	A2, 15-NOV-2001]
AAU01199	Human adenine nucleotide	1 . . . 299	249/300 (83%)	e−137
	translocator-2 (ANT-2) protein -	1 . . . 298	262/300 (87%)
	Homo sapiens, 298 aa.
	[WO200132876-A2, 10-MAY-2001]
AAY71032	Human adenine nucleotide	1 . . . 299	249/300 (83%)	e−137
	translocator ANT2 - Homo sapiens,	1 . . . 298	262/300 (87%)
	298 aa. [WO200026370-A2, 11-MAY-2000]
AAU10380	Human adenine nucleotide	1 . . . 297	235/298 (78%)	e−130
	translocator 3 (ANT3) - Homo	1 . . . 296	255/298 (84%)
	sapiens, 298 aa. [WO200185944-
	A2, 15-NOV-2001]
AAU01200	Human adenine nucleotide	1 . . . 297	235/298 (78%)	e−130
	translocator-3 (ANT-3) protein -	1 . . . 296	255/298 (84%)
	Homo sapiens, 298 aa.
	[WO200132876-A2, 10-MAY-2001]

[0318] In a BLAST search of public sequence datbases, the NOV3a protein was found to have homology to the proteins shown in the BLASTP data in Table 3D.

TABLE 3D
Public BLASTP Results for NOV3a
		NOV3a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q09073	ADP, ATP carrier protein, fibroblast	1 . . . 299	251/300 (83%)	e−138
	isoform (ADP/ATP translocase 2)	1 . . . 298	263/300 (87%)
	(Adenine nucleotide translocator 2)
	(ANT 2) - Rattus norvegicus (Rat),
	298 aa.
P05141	ADP, ATP carrier protein, fibroblast	1 . . . 299	251/300 (83%)	e−138
	isoform (ADP/ATP translocase 2)	1 . . . 298	263/300 (87%)
	(Adenine nucleotide translocator 2)
	(ANT 2) - Homo sapiens (Human),
	298 aa.
P51881	ADP, ATP carrier protein, fibroblast	1 . . . 299	250/300 (83%)	e−137
	isoform (ADP/ATP translocase 2)	1 . . . 298	262/300 (87%)
	(Adenine nucleotide translocator 2)
	(ANT 2) - Mus musculus (Mouse),
	298 aa.
A29132	ADP, ATP carrier protein T2 -	1 . . . 299	249/300 (83%)	e−137
	human, 298 aa.	1 . . . 298	262/300 (87%)
BAB84673	ADENINE NUCLEOTIDE	1 . . . 299	248/300 (82%)	e−137
	TRANSLOCATOR 2 - Bos taurus	1 . . . 298	262/300 (86%)
	(Bovine), 298 aa.

[0319] PFam analysis predicts that the NOV3a protein contains the domains shown in the Table 3E.

TABLE 3E
Domain Analysis of NOV3a
		Identities/
Pfam		Similarities	Expect
Domain	NOV3a Match Region	for the Matched Region	Value
mito_carr	7 . . . 107	32/125 (26%)	2.4e−23
		87/125 (70%)
mito_carr	114 . . . 210	35/125 (28%)	8.7e−17
		82/125 (66%)
mito_carr	211 . . . 299	24/125 (19%)	0.00024
		64/125 (51%)

Example 4

[0320] The NOV4 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 4A.

TABLE 4A
NOV4 Sequence Analysis
                 SEQ ID NO:7          6075 bp
NOV4a,           ACGGCAATGGTTTCTTCCAACCACCACCACCTGACAACCCTGCATGGCGGCTGCCCCC
CG101211-01      TCCGCGCTGCTTCTGCTGCCGCCCTTTCCAGTCCTCTCTACCTATCGGCTCCAGAGCC
DNA Sequence     GCAGTCGTCCTTCCGCCCCAGAGACCGATGATAGTCGAGTTGGGGGCATTATGAGAGG
                 AGAGAAAAACTACTACTTCCGTGGAGCTGCGGGGGACCACGGTTCCTGCCCCACTACA
                 ACTTCGCCTCTGGCCTCGGCCCTCTTGATGCCCTCGGAGGCAGTCTCAAGCAGCTGGT
                 CTGAGTCTGGAGGCGGTTTGTCAGGGGGAGATGAAGAGGACACTCGGCTCCTTCAACT
                 CCTCCGCACTGCCCGGGATCCTTCTGAGGCCTTCCAGGCTTTGCAAGCTGCTTTGCCG
                 CGGCGGGGCGGTCGACTTGGCTTCCCCCGACGCAAGGAAGCTTTGTATCGGGCACTGG
                 GCCGAGTGCTTGTGGAAGGAGGTAGTGATGAGAAGCGGCTCTGCTTGCAACTTCTCTC
                 GGACGTTCTCCGGGGTCAGGGGGAGGCAGGCCAGCTTGAAGAGGCCTTTAGCTTAGCA
                 CTTTTGCCTCAACTAGTTGTCTCGTTACGGGAAGAGAATCCAGCCCTGCGGAAAGATG
                 CGCTGCAGATCCTTCATATATGTCTGAAACGTAGTCCTGGAGAGGTGCTGAGAACGCT
                 TATACAACAAGGACTGGAAAGTACCGATGCCCGACTTAGAGCTTCCACAGCACTACTG
                 CTTCCCATCTTGCTTACTACTGAGCACTTGTTGCTTGGTCTGGATCTCACCGAGGTGA
                 TAATATCCCTAGCCCGAAAGCTTGGTGATCAGGAGACAGAAGAAGAATCTGAGACAGC
                 ATTTCTCGTCTGCCCTCTGCCCTGAGGAGACACTACAATCGCCGCCTGGAGTCCCAGT
                 TTGGAAGTCAGGTTCCTTATTATTTGGAACTTGAAGCCTCTGGATTTCCTGAAGATCC
                 CCTTCCCTGTGCAGTGACTCTTTCCAACAGCAATCTTAAATTTGGGATTATTCCTCAG
                 GAGCTGCATTCACGATTATTGGATCAGGAAGACTATAAGAACCGGACCCAGGCCGTCG
                 TGTTGGCTTCATTAGTTTGCTATATAATTTGTTAGACGATTCTAACTTCAAAGTGGTG
                 CATGGCACACTTGAAGTCCTCCATTTACTGGTTATTCGCCTTGGAGAGCAGGTACAGC
                 AGTTCTTGGGACCAGTTATAGCAGCTTCTGTCAAAGTGCTGGCGGACAACAAGTTGGT
                 GATCAAACAAGAATACATGAAAATCTTCCTCAAGCTAATGAAGGAAGTAGGACCTCAG
                 CAGGTGCTTTGTTTACTCCTGAAACATCTCAAACATAAGCATTCCAGAGTGAGAGAGG
                 AGGTGGTGAACATTTGCATCTGCTCCCTGCTGACCTATCCTAGTGAGGATTTTGACTT
                 GCCCAAACTGTCCTTTGATCTTGCCCCAGCTCTTGTAGATAGCAAACGCAGGGTACGC
                 CAAGCAGCTTTAGAAGCTTTTGCCGTATTGGCATCATCAATGGGCTCAGGTAAAACCA
                 GCATCCTTTTTAAAGCTGTGGATACAGTTGAACTGCAAGATAATGGAGATGGAGTGAT
                 GAATGCTGTGCAGGCCAGATTGGCTAGGAAAACCTTACCAAGGCTCACAGAGCAGGGA
                 TTTGTGGAATATGCAGTACTGATGCCATCTTCTGCCGGGGGTAGGTCAAACCATTTGG
                 CACATGGAGCAGATACGGACTGGCTTTTGGCTGGTAACAGAACTCAGAGTGCACACTG
                 TCACTGTGGTGACCACGTGAGGGATAGCATGCACATTTATGGATCTTACAGCCCAACT
                 ATCTGTACCCGAAGGGTATTAAGTGCAGGAAAAGGAAAAAATAAATTACCATGGGAAA
                 ATGAGCAACCTGGAATCATGGGAGAAAACCAGACCTCCACTTCCAAGGATATAGAGCA
                 GTCAATGATGATTTATGTTTTAGCAGAAAAAGAGTATCAAGAAACTTATTTCAGAATA
                 GTCGGGATTTTAACCCAGATTGTCTTCCTTTATGTGCTGCTGGTACTACTGGGACTCA
                 ACTGGCAGTGTGGGTTCTGACTTACAATTCCTAGGGACAACTAGCAGTCATCAAGAAA
                 AAGTGTATGCTAGCCTCAATTTTGGCAGTAAGACACAGCAAACATTTGGTAGTCAAAC
                 TATCCTGTCTCATCACCTCGAACTAGTCCAAAGCATACATCTCCTCTTATTATATCTC
                 CAAAGAAGTCTCAAGATAATTCTGTTAATTTCTCAAATTCCTGCCCTCTTAAAAGCTT
                 CGAAGGACTATCAAAGCCAAGTCCACAGAAGAAGCTTGTCAGCCAAAAATCGTCTGAT
                 CCTACGGGTAGAAATCATGGAGAAAATTCTCAAGAAAAACCTCCAGTTCAGCTTACAC
                 CTGCCTTGGTGAGATCGCCATCTTCCCGACGAGGTCTAAATGGGACAAAGCCTGTTCC
                 TCCCATACCAAGGGGAATAAGCCTTTTGCCTGATAAAGCTGATTTAAGCACAGTGGGA
                 CACAAAAAGAAAGAGCCTGATGATATTTGGAAGTGTGAAAAAGATAGTCTTCCAATTG
                 ATCTTTCAGAATTAAATTTCAAGGATAAAGATTTGGATCAAGAAGAGATGCATAGCTC
                 TCTTAGGTCCCTTCGTAATAGTGCAGCTAAGAAAAGAGCAAAACTGAGTGGCAGTACT
                 TTAGATCTTGAAAGCCCTGATTCTGCAATGAAGCTCGACTTGACGATGGACTCCCCGT
                 CTCTGTCTTCCTCACCAAACATCAATTCTTACAGTGAAAGTGGAGTTTACAGCCAAGA
                 ATCATTGACTTCTTCTCTGTCTACAACTCCCCAGGGGAAGAGAATAATGTCAGACATA
                 TTTCCAACATTTGGGTCAAAACCTTGTCCAACAAGACTTTCTTCTGCAAAGAAAAAAA
                 TTTCTCATATTGCTGAACAAAGCCCCAGTGCAGGGTCATCATCAAATCCACAGCAAAT
                 TTCCAGTTTTGACTTCACAACCACAAAGGCTTTATCAGAAGACTCAGTAGTAGTTGTT
                 GGAAAAGGCGTATTTGGAAGTTTAAGTTCAGCACCAGCAACCTGCAGCCAATCAGTGA
                 TATCTTCTGTGGAAAATGGGGATACATTTTCAATTAAACAAAGTATTGAACCACCATC
                 AGGGATTTATGGAAGATCAGTCCAGCAAAATATTTCATCATATCTTGATGTTGAGAAT
                 GAAAAAGATGCTAAAGTTTCTATTTCTAAATCTACTTATAACAAGATGAGACAAAAGA
                 GAAAAGAAGAGAAAGAACTGTTTCACAATAAAGATTGTGAAAAGAAGGAAAAAAATTC
                 CTGGGAACGAATGAGACATACAGGAACTGAGAAAATGGCATCTGAAAGTGAAACACCT
                 ACTGGAGCTATTTCACAGTATAAAGAAAGGATGCCTTCTGTCACTCATAGTCCAGAAA
                 TAATGGATCTGTCAGAACTACGACCATTCTCTAAACCAGAAATAGCACTGACAGAAGC
                 CCTGAGGCTTTTGGCTGATGAGGATTGGGAGAAGAAAATTGAGGGACTGAATTTTATT
                 AGATGCTTAGCTGCTTTTCATTCTGAGATACTGAACACAAAGTTGCATGAAACAAATT
                 TTGCAGTTGTTCAAGAGGTGAAAAATTTACGTTCTGGAGTTTCTCGTGCTGCTGTGGT
                 CTGTTTAAGTGATCTTTTCACTTATTTGAAAAAGAGCATGGATCAAGAGCTAGATACC
                 ACAGTAAAAGTTTTGTTGCACAAGGCTGGTGAATCAAATACATTTATAAGAGAAGATG
                 TTGACAAAGCATTGAGAGCTATGGTTAATAATGTAACTCCTGCACGTGCAGTTGTTTC
                 TCTTATCAATGGTGGACAAAGGTATTATGGTCGAAAGATGCTGTTCTTCATGATGTGT
                 CATCCTAACTTTGAAAAAATGCTTGAAAAGTATGTCCCATCTAAAGATTTGCCATATA
                 TTAAGGACTCTGTTAGAAACTTACAGCAAAAGGGTTTGGGGGAGATACCATTAGATAC
                 TCCTTCAGCAAAAGGAAGACGATCTCATACTGGCAGTGTTGGAAATACAAGATCATCA
                 TCTGTTTCTAGAGATGCTTTCAATTCAGCTGAAAGAGCTGTAACTGAAGTTCGTGAAG
                 TCACCAGAAAATCAGTCCCTCGTAATTCCTTAGAAAGTGCTGAGTACCTTAAACTCAT
                 AACTGGCTTATTAAATGCAAAAGACTTTCGTGATCGTATTAATGGGATTAAGCAGCTT
                 TTATCAGATACAGAAAATAATCAAGACCTTGTTGTTGGAAACATTGTGAAGATTTTTG
                 ATGCTTTTAAATCTCGACTTCATGATTCTAATAGTAAAGTAAATCTGGTGGCTCTGGA
                 AACAATGCACAAAATGATTCCTCTACTTAGAGACCACTTATCTCCTATAATCAACATG
                 CTAATTCCAGCAATAGTGGATAACAATCTGAATTCCAAGAATCCAGGCATCTATGCGG
                 CTGCTACAAATGTTGTTCAGGCACTGAGTCAGCATGTAGACAATTACTTACTTCTACA
                 GCCATTTTGCACAAAAGCTCAGTTTTTAAATGGAAAAGCAAAACAGGACATGACGGAA
                 AAGCTTGCTGATATTGTTACGGAACTTTATCAAAGGAAGCCGCATGCCACAGAGCAGA
                 AAGTGTTGGTTGTTTTATGGCATCTCTTAGGAAATATGACAAATAGTGGCTCTCTGCC
                 TGGAGCTGGAGGAAATATACGAACAGCCACAGCTAAATTATCAAAAGCACTCTTTGCA
                 CAGATGGGTCAGAATCTGTTAAATCAGGCTGCATCTCAACCACCACATATCAAAAAGA
                 GTTTGGAGGAATTACTCGATATGACAATTTTAAATGAATTATGAATCTTCGATAAAAT
                 ACTGTATGATGAACAAAAGTGTTTACATGATGACAAATGGAACTTTCTAAAAGTTATG
                 TTATCAGTGCCTGCACTTCACATCCAGCAAATTAAGTCAATGGCTATTTTTATTTGCA
                 GCCTATGAGTACACATCTGTCCTATATCAACCTTACCACTTATATTCATCACATAAAA
                 ACCTAAAATATTCATGAATAATTCATGAAATCTGAGTCACATGGGATGAATTCAATTT
                 TAATATTTTTGAGAAAAGTCCTGCTCATTTGCACTATTCTATAGAAACTACAATTTGT
                 TGCCCTATATGTAAAATTAGAATTGTAATTAAAAATACACATTTTATTATGTAATCAT
                 GTTCTGGTATGTCTCATTTCTCAGCCTTATTTTATAACGTGGAAGTCATTGAACTATG
                 TTATCAGAAACTAAGTTTGTATATTATTTGTGAAAAACATGTATTTCTGAATCAGTCC
                 GCTAATATGATTGTGCAGTATTAGCTTGCTTTTGCTGCTGTGTTAATGTCATATATTT
                 GCTTACCTTTTGGGTTCAATTATCTACATAATTGTGAAATTTAACAAGTTATAATAAA
                 GCATGACAACCAAAGTTTTAGAAAACATTAAACATTTTAAATGCACGTTTAAAAAACG
                 TGTTGAATGTAACCCCCCTATTTTTGTGTGCAAACACTAAATTTTATTGCTTTATGTT
                 TTGACCTTTATAAAGGTGTTATTCTGCTGCCCAGTTTTGTAATTCTCAAAAATAGTGC
                 CAGGTCTTCTATAGCTTTTTTCAGAATTCATGGGCTTACAAGTACTGTATGCATCTTT
                 AAAAAGAAAAGGAATGTTATAAAATAAAAGGATTTATTTCTTT
                 ORF Start: ATG at 44 ORF Stop: TGA at 5204
                 SEQ ID NO:8          1720 aa MW at 189383.1 kD
NOV4a,           MAAAPSALLLLPPFPVLSTYRLQSRSRPSAPETDDSRVGGIMRGEKNYYFRGAAGDHG
CG101211-01      SCPTTTSPLASALLMPSEAVSSSWSESGGGLSGGDEEDTRLLQLLRTARDPSEAFQAL
Protein Sequence QAALPRRGGRLGFPRRKEALYRALGRVLVEGGSDEKRLCLQLLSDVLRGQGEAGQLEE
                 AFSLALLPQLVVSLREENPALRKDALQILHICLKRSPGEVLRTLIQQGLESTDARLRA
                 STALLLPILLTTEDLLLGLDLTEVIISLARKLGDQETEEESETAFSALQQIGERLGQD
                 RFQSYISRLPSALRRHYNRRLESQFGSQVPYYLELEASGFPEDPLPCAVTLSNSNLKF
                 GIIPQELHSRLLDQEDYKNRTQAVEELKQVLGKFNPSSTPHSSLVGFISLLYNLLDDS
                 NFKVVHGTLEVLHLLVIRLGEQVQQFLGPVIAASVKVLADNKLVIKQEYMKIFLKLMK
                 EVGPQQVLCLLLKHLKHKHSRVREEVVNICICSLLTYPSEDFDLPKLSFDLAPALVDS
                 KRRVRQAALEAFAVLASSMGSGKTSILFKAVDTVELQDNGDGVMNAVQARLARKTLPR
                 LTEQGFVEYAVLMPSSAGGRSNHLAHGADTDWLLAGNRTQSAHCHCGDHVRDSMHIYG
                 SYSPTICTRRVLSAGKGKNKLPWENEQPGIMGENQTSTSKDIEQFSTYDFIPSAKLKL
                 SQGMPVNDDLCFSRKRVSRNLFQNSRDFNPDCLPLCAAGTTGTHQTNLSGKCAQLGFS
                 QICGKTGSVGSDLQFLGTTSSHQEKVYASLNFGSKTQQTFGSQTECTSSNGQNPSPGA
                 YILPSYPVSSPRTSPKHTSPLIISPKKSQDNSVNFSNSWPLKSFEGLSKPSPQKKLVS
                 QKSSDPTGRNHGENSQEKPPVQLTPALVRSPSSRRGLNGTKPVPPIPRGISLLPDKAD
                 LSTVGHKKKEPDDIWKCEKDSLPIDLSELNFKDKDLDQEEMHSSLRSLRNSAAKKRAK
                 LSGSTLDLESPDSAMKLDLTMDSPSLSSSPNINSYSESGVYSQESLTSSLSTTPQGKR
                 IMSDIFPTFGSKPCPTRLSSAKKKISHIAEQSPSAGSSSNPQQISSFDFTTTKALSED
                 SVVVVGKGVFGSLSSAPATCSQSVISSVENGDTFSIKQSIEPPSGIYGRSVQQNISSY
                 LDVENEKDAKVSISKSTYNKMRQKRKEEKELFHNKDCEKKEKNSWERMRHTGTEKMAS
                 ESETPTGAISQYKERMPSVTHSPEIMDLSELRPFSKPEIALTEALRLLADEDWEKKIE
                 GLNFIRCLAAFHSEILNTKLHETNFAVVQEVKNLRSGVSRAAVVCLSDLFTYLKKSMD
                 QELDTTVKVLLHKAGESNTFIREDVDKALRAMVNNVTPARAVVSLINGGQRYYGRKML
                 FFMMCHPNFEKMLEKYVPSKDLPYIKDSVRNLQQKGLGEIPLDTPSAKGRRSHTGSVG
                 NTRSSSVSRDAFNSAERAVTEVREVTRKSVPRNSLESAEYLKLITGLLNAKDFRDRIN
                 GIKQLLSDTENNQDLVVGNIVKIFDAFKSRLHDSNSKVNLVALETMHKMIPLLRDHLS
                 PIINMLIPAIVDNNLNSKNPGIYAAATNVVQALSQHVDNYLLLQPFCTKAQFLNGKAK
                 QDMTEKLADIVTELYQRKPHATEQKVLVVLWHLLGNMTNSGSLPGAGGNIRTATAKLS
                 KALFAQMGQNLLNQAASQPPHIKKSLEELLDMTILNEL

[0321] Further analysis of the NOV4a protein yielded the following properties shown in Table 4B.

TABLE 4B
Protein Sequence Properties NOV4a
PSort     0.5231 probability located in outside;
analysis: 0.1900 probability located in lysosome (lumen);
          0.1000 probability located in endoplasmic reticulum
          (membrane);
          0.1000 probability located in endoplasmic reticulum (lumen)
SignalP   Cleavage site between residues 19 and 20
analysis:

[0322] 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.

TABLE 4C
Geneseq Results for NOV4a
		NOV4a
		Residues/	Identities/
Geneseq	Protein/Organism/Length	Match	Similarities for the	Expect
Identifier	[Patent #, Date]	Residues	Matched Region	Value
AAM78886	Human protein SEQ ID NO	1 . . . 1720	1716/1720 (99%)	0.0
	1548 - Homo sapiens, 1720 aa.	1 . . . 1720	1719/1720 (99%)
	[WO200157190-A2, 09-AUG-2001]
AAM79870	Human protein SEQ ID NO	1 . . . 1720	1710/1721 (99%)	0.0
	3516 - Homo sapiens, 1721 aa.	1 . . . 1721	1714/1721 (99%)
	[WO200157190-A2, 09-AUG-2001]
ABG10016	Novel human diagnostic protein #	42 . . . 1714	1673/1673 (100%)	0.0
	10007 - Homo sapiens, 1677	1 . . . 1673	1673/1673 (100%)
	aa. [WO200175067-A2, 11-OCT-2001]
ABG10016	Novel human diagnostic protein #	42 . . . 1714	1673/1673 (100%)	0.0
	10007 - Homo sapiens, 1677	1 . . . 1673	1673/1673 (100%)
	aa. [WO200175067-A2, 11-OCT-2001]
ABG10018	Novel human diagnostic protein #	1385 . . . 1690	278/307 (90%)	e−151
	10009 - Homo sapiens, 1047	27 . . . 322	281/307 (90%)
	aa. [WO200175067-A2, 11-OCT-2001]

[0323] In a BLAST search of public sequence datbases, the NOV4a protein was found to have homology to the proteins shown in the BLASTP data in Table 4D.

TABLE 4D
Public BLASTP Results for NOV4a
		NOV4a
Protein		Residues/	Identities/
Accession		Match	Similarities for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
BAA24853	KIAA0423 PROTEIN - Homo	1 . . . 1720	1720/1720 (100%)	0.0
	sapiens (Human), 1723 aa	4 . . . 1723	1720/1720 (100%)
	(fragment).
Q9Y4F4	KIAA0423 PROTEIN - Homo	25 . . . 1720	1696/1696 (100%)	0.0
	sapiens (Human), 1696 aa	1 . . . 1696	1696/1696 (100%)
	(fragment).
Q17423	B0024.8 PROTEIN -	131 . . . 615	137/504 (27%)	2e−35
	Caenorhabditis elegans, 1185 aa.	59 . . . 535	233/504 (46%)
T18643	hypothetical protein B0024.8 -	131 . . . 625	141/518 (27%)	1e−34
	Caenorhabditis elegans, 537	59 . . . 522	230/518 (44%)
	aa.
Q9VPK5	CG4648 PROTEIN -	1232 . . . 1386	51/160 (31%)	1e−16
	Drosophila melanogaster	701 . . . 860	86/160 (52%)
	(Fruit fly), 953 aa.

[0324] PFam analysis predicts that the NOV4a protein contains the domains shown in the Table 4E.

TABLE 4E
Domain Analysis of NOV4a
Pfam	NOV4a Match Region	Identities/	Expect Value
Domain		Similarities
		for the Matched
		Region

Example 5

[0325] The NOV5 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 5A.

TABLE 5A
NOV5 Sequence Analysis
                 SEQ ID NO:9      653 bp
NOV5a,           GCCCTCGGCCTGAGTCGGGATGGAGCTGCCTGCTGTGAACCTGAAGGTGATTCTCCTA
CG101274-01      GGTCACTGGCTGCTGACAACCTGGGGCTGCATTGTATCCTCAGGCTCCTATGCCTGGG
DNA Sequence     CCAACTTCACCATCCTGGCCTTGGGCGTGTGGGCTGTGGCTCAGCGGGACTCCATCGA
                 CGCCATAAGCATGTTTCTGGGTGGCTTGCTCGCCACCATCTTCCTGGACATCGTGCAC
                 ATCAGCATCTTCTACCCGCGGGTCAGCCTCACGGACACGGGCCGCTTTGGCGTGGGCA
                 TGGCCATCCTCAGCTTGCTGCTCAAGCCGCTCTCCTGCTGCTTCGTCTACCACATGTA
                 CCGGGAGCGCGGGGGTGAGCTCCTGGTCCACACTGGTNTCCTTGGGTCTTCTCAGGAC
                 CGTAGTGCCTACCAGACGATTGACTCAGCAGAGGCGCCCGCAGATCCCTTGCAGTCCC
                 GAAGGCAGGAGTCAGATCCCGAGGGTCTGAGCCAGCCGCTGCCGGCCTCCCGGCCTCT
                 CTCTGGAGGGTTAGGTTCTACCCTTTGACCAAGATTTCCCTGGTTGAATAGGGACCGG
                 TCCCCTTCCTTTATTTCCTTTTTTTTTAGCATCAAAAAAGATCCGCACAGAGGCTTTC
                 TTNNNNNNNNNNNNN
                 ORF Start: at 14 ORF Stop: at 542
                 SEQ ID NO:10     176 aa MW at 18893.6 kD
NOV5a,           MELPAVNLKVILLGHWLLTTWGCIVSSGSYAWANFTILALGVWAVAQRDSIDAISMFL
CG101274-01      GGLLATIFLDIVHISIFYPRVSLTDTGRFGVGMAILSLLLKPLSCCFVYHMYRERGGE
Protein Sequence LLVHTGXLGSSQDRSAYQTIDSAEAPADPLQSRRQESDPEGLSQPLPASRPLSGGLGS
                 TL

[0326] Further analysis of the NOV5a protein yielded the following properties shown in Table 5B.

TABLE 5B
Protein Sequence Properties NOV5a
PSort     0.6000 probability located in plasma membrane;
analysis: 0.4000 probability located in Golgi body;
          0.3000 probability located in endoplasmic reticulum
          (membrane); 0.1000 probability located in mitochondrial
          inner membrane
SignalP   Cleavage site between residues 23 and 24
analysis:

[0327] 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.

TABLE 5C
Geneseq Results for NOV5a
		NOV5a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAB73100	Human angiotensin II-I receptor -	1 . . . 160	148/160 (92%)	1e−79
	Homo sapiens, 159 aa.	1 . . . 154	149/160 (92%)
	[WO200119864-A1, 22-MAR-2001]
AAM25822	Human protein sequence SEQ ID	1 . . . 160	148/160 (92%)	1e−79
	NO: 1337 - Homo sapiens, 161 aa.	3 . . . 156	149/160 (92%)
	[WO200153455-A2, 26-JUL-2001]
AAM79565	Human protein SEQ ID NO: 3211 -	1 . . . 160	148/160 (92%)	1e−79
	Homo sapiens, 161 aa.	3 . . . 156	149/160 (92%)
	[WO200157190-A2, 09-AUG-2001]
AAM78581	Human protein SEQ ID NO: 1243 -	1 . . . 160	148/160 (92%)	1e−79
	Homo sapiens, 159 aa.	1 . . . 154	149/160 (92%)
	[WO200157190-A2, 09-AUG-2001]
ABB12006	Human glioblastoma-derived	1 . . . 160	148/160 (92%)	1e−79
	protein homologue, SEQ ID	3 . . . 156	149/160 (92%)
	NO: 2376 - Homo sapiens, 161 aa.
	[WO200157188-A2, 09-AUG-2001]

[0328] In a BLAST search of public sequence datbases, the NOV5a protein was found to have homology to the proteins shown in the BLASTP data in Table 5D.

TABLE 5D
Public BLASTP Results for NOV5a
		NOV5a	Identities/
Protein		Residues/	Similarities for the
Accession		Match	Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q96PL4	AGTRAP PROTEIN - Homo	1 . . . 160	148/160 (92%)	3e−79
	sapiens (Human), 159 aa.	1 . . . 154	149/160 (92%)
Q9NRW9	ATRAP - Homo sapiens (Human),	1 . . . 160	148/160 (92%)	3e−79
	159 aa.	1 . . . 154	149/160 (92%)
Q96AC0	SIMILAR TO ANGIOTENSIN II,	1 . . . 160	141/160 (88%)	7e−73
	TYPE I RECEPTOR-	1 . . . 147	142/160 (88%)
	ASSOCIATED PROTEIN - Homo
	sapiens (Human), 152 aa.
Q9WVK0	AT1 RECEPTOR-ASSOCIATED	1 . . . 157	117/160 (73%)	2e−60
	PROTEIN - Mus musculus	1 . . . 160	130/160 (81%)
	(Mouse), 161 aa.
Q9D940	ANGIOTENSIN II, TYPE I	1 . . . 148	115/149 (77%)	3e−60
	RECEPTOR-ASSOCIATED	1 . . . 149	125/149 (83%)
	PROTEIN - Mus musculus
	(Mouse), 161 aa.

[0329] PFam analysis predicts that the NOV5a protein contains the domains shown in the Table 5E.

TABLE 5E
Domain Analysis of NOV5a
Pfam	NOV5a Match Region	Identities/	Expect
Domain		Similarities	Value
		for the Matched Region

Example 6

[0330] The NOV6 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 6A.

TABLE 6A
NOV6 Sequence Analysis
                 SEQ ID NO:11          1980 bp
NOV6a,           GGTCCCTGGACGCGGAACAGAGATCCCCTGATTCAGCCACCCCCAGACTGAGCCCCGT
CG101904-01      AGAGTGCGTTCTTACCTTCCTGCCCCGACGAAGGTCCCAGAGACGCTGCGGACAACAC
DNA Sequence     CAGCATGTCGAGCGAGCAGAGCGCGCCGGGGGCCTCACCCAGGGCCCCGCGTCCGGGG
                 ACCCAGAAGTCTTCTGGCGCGGTGACCAAAAAGGGAGAGCGCGCGGCCAAAGAGAAGC
                 CAGCGACCGTTCTGCCTCCCGTGGGGGAGGAGGAGCCCAAAAGCCCTGAGGAGTACCA
                 GTGCTCCGGGGTCCTCGAGACCGACTTCGCCGAGCTCTGCACGCGGTGGGGCTACACG
                 GACTTCCCCAAAGTTGTCAACCGGCCCCGCCCCCACCCGCCCTTCGTCCCCTCCGCCT
                 CTTTGTCGGAAAAGGCCACCTTAGACGATCCGCGGCTGTCGGGGTCCTGCAGCCTCAA
                 TAGCCTGGAGAGCAAATACGTGTTCTTCCGGCCCACCATCCAGGTGGAGCTGGAGCAG
                 GAGGACAGCAAGTCAGTGAAGGAAATCTACATCCGCGGTTGGAAGGTTGAGGAACGGA
                 TTCTGGGTGTCTTCTCTAAATGTCTGCCCCCGCTTACCCAGCTACAGGCCATCAACTT
                 GTGGAAGGTGGGGCTGACCGATAAGACCCTGACCACCTTCATCGAGCTCCTGCCTCTC
                 TGTTCATCCACGCTCAGAGGTTCTCGCTCTCCTTCCTGGCTGCCTGGGGCTCTGGCCC
                 TGTACTGGGGGCTGATCTCCCCTGCCCTCAGGAAGGTGTCTCTGGAGGGGAACCCACT
                 GCCGGAGCAGTCCTATCACAAGCTCATGGCCTTGGACAGCACGATTGCGCACTTGTCT
                 CTGCGGAACAATAACATCGACGACCGCGGGGCGCAACTCCTGGGCCAGGCGCTGTCCA
                 CGCTGCACAGCTGCAACCGGACCCTCGTCTCGCTCAACCTGGGTTTCAACCACATCGG
                 TGACGAGGGCGCAGGCTACATCGCGGACGGCCTCCGGCTGAACCGTTCCCTGCTCTGG
                 CTGTCCCTGGCCCACAACCGCATCCAGGACAAGGGCGCCCTGAAGCTGGCTGAGGTCC
                 TGCGCGCCTTCGAGCTGACACACACCGAAGTGGTGGAGCGCCGACGCCTCCTGCTGGA
                 AAAAGGGACACAGGAGCGCTCGCGATCGCCCTCCTCCTCTCGACACGGGGACTCCAAA
                 ACGGACCGTGAGAAGAGTCAGATGGTAGGGATCAGCAATAGTGCATTGGTGGACAAGA
                 CAGACAAGACGCAGACAATGAAAACCCCTAAGGGCCTGGGCAAGAAAAAGGAGAAATC
                 ATGGGAATTGGCCAAGAAAGAGGAGAAGTTGGGGTCTGGGCAGTCACCCACACAAGGA
                 ACCCCTAAGAAGGAAGATGCCACAAAGGCAGGCAAGGGGAAGGTAACCATCCCTGAAC
                 AGAAGCCAAGCAGGGCAAAAGGGATCAAGATCGGGAGCAGAGAGAAGCGCAGCATCCT
                 CCTGGAGTCCGAGCTGGTTGTTGAGGCTACTGAGGTGGTCAACCCTCTCCTGGAGCCT
                 GTGGAGCACCGAGATGGGAAAGTTTTCATGCCTGGGAACAAGGTCCTTTTGCACCTCA
                 ACCTCATCCGGAACCGCATCACAGAGGTGGGGCTGGAGGGCTTCCTCGCCACGGTGCA
                 GTATCAGATGCAGTTCTCCAAGGCCAAGAGTGCATCCAAGGGTCCAGTGGGGCTGCTG
                 TGGCTGTCCCTGGCTAAAAATTGCTTCGCCCCACAATGTCCTGCGTACGCCATAATCC
                 AGGAGCTGATGTTGCCAAGGGATCCCATCAAGGCCAAACTCAGGGAGGATGAGGCCAT
                 GGCATTCTTCCCCTAGCCCCCTCCCACCTGCTTGCCTCTAAGACTCGGGGCTACAGAA
                 GCACCTCCTGTCCCTGTGTGGGGTGACCTCCCTGGGGGAGATCTCAGACCAATAACAA
                 AGTCTGTT
                 ORF Start: ATG at 121 ORF Stop: TAG at 1870
                 SEQ ID NO:12          583 aa MW at 64375.2 kD
NOV6a,           MSSEQSAPGASPRAPRPGTQKSSGAVTKKGERAAKEKPATVLPPVGEEEPKSPEEYQC
CG101904-01      SGVLETDFAELCTRWGYTDFPKVVNRPRPHPPFVPSASLSEKATLDDPRLSGSCSLNS
Protein Sequence LESKYVFFRPTIQVELEQEDSKSVKEIYIRGWKVEERILGVFSKCLPPLTQLQAINLW
                 KVGLTDKTLTTFIELLPLCSSTLRGSRSPSWLPGALALYWGLISPALRKVSLEGNPLP
                 EQSYHKLMALDSTIAHLSLRNNNIDDRGAQLLGQALSTLHSCNRTLVSLNLGFNHIGD
                 EGAGYIADGLRLNRSLLWLSLAHNRIQDKGALKLAEVLRAFELTHTEVVERRRLLLEK
                 GTQERSRSPSSSRHGDSKTDREKSQMVGISNSALVDKTDKTQTMKTPKGLGKKKEKSW
                 ELAKKEEKLGSGQSPTQGTPKKEDATKAGKGKVTIPEQKPSRAKGIKIGSREKRSILL
                 ESELVVEATEVVNPLLEPVEHRDGKVFMPGNKVLLHLNLIRNRITEVGLEGFLATVQY
                 QMQFSKAKSASKGPVGLLWLSLAKNCFAPQCPAYAIIQELMLPRDPIKAKLREDEAMA
                 FFP

[0331] Further analysis of the NOV6a protein yielded the following properties shown in Table 6B.

TABLE 6B
Protein Sequence Properties NOV6a
PSort     0.4500 probability located in cytoplasm;
analysis: 0.3000 probability located in microbody (peroxisome);
          0.1000 probability located in mitochondrial matrix space;
          0.1000 probability located in lysosome (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0332] 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.

TABLE 6C
Geneseq Results for NOV6a
		NOV6a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAG79119	Amino acid sequence of	221 . . . 328	43/111 (38%)	1e−07
	inflammatory bowel disease 1	846 . . . 952	57/111 (50%)
	(IBD1) protein - Homo sapiens,
	1041 aa. [FR2806739-A1, 28-SEP-2001]
ABG14217	Novel human diagnostic protein #	220 . . . 329	38/115 (33%)	2e−06
	14208 - Homo sapiens, 356 aa.	165 . . . 275	58/115 (50%)
	[WO200175067-A2, 11-OCT-2001]
ABG14217	Novel human diagnostic protein #	220 . . . 329	38/115 (33%)	2e−06
	14208 - Homo sapiens, 356 aa.	165 . . . 275	58/115 (50%)
	[WO200175067-A2, 11-OCT-2001]
AAR35073	Mouse t-complex associated testes	208 . . . 330	45/150 (30%)	2e−06
	expressed protein 1 - Mus musculus,	320 . . . 469	67/150 (44%)
	497 aa. [WO9306859-A, 15-APR-1993]
AAU80865	Human CARD3X protein #2 - Homo	224 . . . 328	41/105 (39%)	3e−06
	sapiens, 1009 aa. [WO200190156-	770 . . . 870	56/105 (53%)
	A2, 29-NOV-2001]

[0333] In a BLAST search of public sequence datbases, the NOV6a protein was found to have homology to the proteins shown in the BLASTP data in Table 6D.

TABLE 6D
Public BLASTP Results for NOV6a
		NOV6a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9D3W5	4933430H15RIK PROTEIN -	1 . . . 580	452/581 (77%)	0.0
	Mus musculus (Mouse), 558 aa.	1 . . . 557	492/581 (83%)
Q96M24	CDNA FLJ32884 FIS, CLONE	240 . . . 549	307/311 (98%)	e−170
	TESTI2004229 - Homo sapiens	1 . . . 311	308/311 (98%)
	(Human), 354 aa.
BAB84935	FLJ00180 PROTEIN - Homo	216 . . . 329	45/117 (38%)	2e−10
	sapiens (Human), 499 aa	125 . . . 237	66/117 (55%)
	(fragment).
Q93ZV8	HYPOTHETICAL 64.7 KDA	208 . . . 329	48/127 (37%)	9e−10
	PROTEIN - Arabidopsis thaliana	326 . . . 448	72/127 (55%)
	(Mouse-ear cress), 605 aa.
AAM22460	CARD15-LIKE PROTEIN-	226 . . . 329	43/107 (40%)	5e−09
	Homo sapiens (Human), 195 aa	1 . . . 103	60/107 (55%)
	(fragment).

[0334] PFam analysis predicts that the NOV6a protein contains the domains shown in the Table 6E.

TABLE 6E
Domain Analysis of NOV6a
Pfam	NOV6a Match Region	Identities/	Expect
Domain		Similarities	Value
		for the Matched Region

Example 7

[0335] The NOV7 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 7A.

TABLE 7A
NOV7 Sequence Analysis
	SEQ ID NO:13	687 bp
NOV7a,	TTGACTGTATCGCCGGAATTCATGACCACGCTGGCCGGCGCTGTGCCCAGGATGATGC
CG102016-01	GGGCGGGCCCGGGGGAAAATAACCCGCGTAGCGGGTTCCCGCTGGAAGTGTCCACTCC	TAA
DNA Sequence	CCTCGGCCAGGGCCGCGTCAACCAGCTCGGCGGCGTTTTTATCAACGGCAGGCCGCTG
	CCCAACCACATCCGCCACAAGATCGTGGAGATGGCCCACCACGGCATCCGGCCCTGCG
	TCATCTCGCGCCAGCTGCGCGTGTCCCACGGCTGCGTCTCCAAGATCCTGTCCAGGTA
	CCAGGAGACTGGCTCCATACGTCCTGGTGCCATCGGCGGCAGCAAGCCCAAGGTGACA
	ACGCCTGACGTGGAGAAGAAAATTGAGGAATACAAAAGAGAGAACCCGGGCATGTTCA
	GCTGGGAAATCCGAGACAAATTACTCAAGGACGCGGTCTGTGATCGAAACACCGTGCC
	GTCAGTGAGTTCCATCAGCCGCATCCTGAGAAGTAAATTCGGGAAAGGTGAAGAGGAG
	GAGGCCGACTTGGAGAGGAAGGAGGCAGAGGAAAGCGAGAAGAAGGCCAAACACAGCA
	TCGACGGCATCCTGAGCGAGCGAGGTAAGCGGTGGCGCCTTGGGCGGCGCACTTGCTG
	GGTGACTTGGAGGCATCGGCTAGCTGACTGCAGCCAAGCTAATTCCGG
	ORF Start: ATG at 22	ORF Stop: TGA at 664
	SEQ ID NO:14	214 aa MW at 23933.3 kD
NOV7a,	MTTLAGAVPRMMRAGPGENNPRSGFPLEVSTPLGQGRVNQLGGVFINGRPLPNHIRHK
CG102016-01	IVEMAHHGIRPCVISRQLRVSHGCVSKILCRYQETGSIRPGAIGGSKPKVTTPDVEKK
Protein Sequence	IEEYKRENPGMFSWEIRDKLLKDAVCDRNTVPSVSSISRILRSKFGKGEEEEADLERK
	EAEESEKKAKHSIDGILSERGKRWRLGRRTCWVTWRASAS

[0336] Further analysis of the NOV7a protein yielded the following properties shown in Table 7B.

TABLE 7B
Protein Sequence Properties NOV7a
PSort     0.7600 probability located in nucleus;
analysis: 0.1000 probability located in mitochondrial matrix space;
          0.1000 probability located in lysosome (lumen);
          0.0000 probability located in endoplasmic reticulum
          (membrane)
SignalP   No Known Signal Sequence Predicted
analysis:

[0337] 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.

TABLE 7C
Geneseq Results for NOV7a
		NOV7a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
ABG20865	Novel human diagnostic protein #	1 . . . 194	191/195 (97%)	e−107
	20856 - Homo sapiens, 837 aa.	1 . . . 195	192/195 (97%)
	[WO200175067-A2, 11-OCT-2001]
ABG20865	Novel human diagnostic protein #	1 . . . 194	191/195 (97%)	e−107
	20856 - Homo sapiens, 837 aa.	1 . . . 195	192/195 (97%)
	[WO200175067-A2, 11-OCT-2001]
ABB62623	Drosophila melanogaster	34 . . . 160	100/127 (78%)	8e−56
	polypeptide SEQ ID NO 14661 -	4 . . . 130	116/127 (90%)
	Drosophila melanogaster, 590 aa.
	[WO200171042-A2, 27-SEP-2001]
ABB59840	Drosophila melanogaster	24 . . . 191	108/168 (64%)	5e−55
	polypeptide SEQ ID NO 6312 -	14 . . . 158	122/168 (72%)
	Drosophila melanogaster, 427 aa.
	[WO200171042-A2, 27-SEP-2001]
ABG26810	Novel human diagnostic protein #	14 . . . 162	102/153 (66%)	5e−52
	26801 - Homo sapiens, 529 aa.	69 . . . 221	119/153 (77%)
	[WO200175067-A2, 11-OCT-2001]

[0338] In a BLAST search of public sequence datbases, the NOV7a protein was found to have homology to the proteins shown in the BLASTP data in Table 7D.

TABLE 7D
Public BLASTP Results for NOV7a
		NOV7a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
I54276	PAX3A protein - human, 215 aa.	1 . . . 214	211/215 (98%)	e−120
		1 . . . 215	212/215 (98%)
Q96H85	PAIRED BOX GENE 3	1 . . . 194	191/194 (98%)	e−108
	(WAARDENBURG	1 . . . 194	192/194 (98%)
	SYNDROME 1) - Homo sapiens
	(Human), 835 aa.
I68547	PAX3B protein - human, 206 aa.	1 . . . 196	193/197 (97%)	e−108
		1 . . . 197	194/197 (97%)
AAF20054	PAX3-FORKHEAD FUSION	1 . . . 194	191/195 (97%)	e−107
	PROTEIN - Homo sapiens	1 . . . 195	192/195 (97%)
	(Human), 836 aa.
Q9CXI6	PAIRED BOX GENE 3 - Mus	1 . . . 194	191/195 (97%)	e−107
	musculus (Mouse), 479 aa.	1 . . . 195	192/195 (97%)

[0339] PFam analysis predicts that the NOV7a protein contains the domains shown in the Table 7E.

TABLE 7E
Domain Analysis of NOV7a
		Identities/
Pfam		Similarities	Expect
Domain	NOV7a Match Region	for the Matched Region	Value
PAX	34 . . . 158	106/125 (85%)	1.1e−92
		125/125 (100%)

Example 8

[0340] The NOV8 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 8A.

TABLE 8A
NOV8 Sequence Analysis
                 SEQ ID NO:15         1305 bp
NOV8a,           GCCGCCAGCCCCGCCGAGGGGAGCCAGCGCCGTCTCTGAGGGGCGTCCGGCGCCGGAG
CG102092-01      CCATGACCCTCCGCCGACTCAGGAAGCTGCAGCAGAAGGAGGAGGCGGCGGCCACCCC
DNA Sequence     GGACCCCGCCGCCCGGACTCCCGACTCGGAAGTCGCGCCCGCCGCTCCGGTCCCGACC
                 CCGGGACCCCCTGCCGCAGCCGCCACCCCTGGGCCCCCAGCGGACGAGCTGTACGCGG
                 CGCTGGAGGACTATCACCCTGCCGAGCTGTACCGCGCGCTCGCCGTGTCCGGGGGCAC
                 CCTGCCCCGCCGAAAGGGCTCAGGATTCCGCTGGAAGAATCTCAGCCAGAGTCCTGAA
                 CAGCAGCGGAAAGTGCTGACGTTGGAGAAGGAGGATAACCAGACCTTCGGCTTTGAGA
                 TCCAGACTTATGGCCTTCACCACCGGGAGGAGCAGCGTGTGGAAATGGTGACCTTTGT
                 CTGCCGAGTTCATGAGTCTAGCCCTGCCCAGCTGGCTGGGCTCACACCAGGGGACACC
                 ATCGCCAGCGTCAATGGCCTGAATGTGGAAGGCATCCGGCATCGAGAGATTGTGGACA
                 TCATTAAGGCGTCAGGCAATGTTCTCAGACTGGAAACTCTATATGGGACATCAATTCG
                 GAAGGCAGAACTGGAGGCTCGTCTGCAGTACCTGAAGCAAACCCTGTATGAGAAGTGG
                 GGAGAGTACAGGTCCCTAATGGTGCAGGAGCAGCGGCTGGTGCATGGCCTGGTGGTGA
                 AGGACCCCAGCATCTACGACACGCTGGAGTCGGTGCGCTCCTGCCTCTACGGCGCGGG
                 CCTGCTCCCGGGCTCGCTGCCCTTCGGGCCTCTGCTCGCCGTGCCCGGGCGTCCCCGC
                 GGAGGCGCCCGACGGGCCAGGGGCGACGCCGACGACGCCGTCTACCACACGTGCTTCT
                 TCGGGGACTCCGAGCCGCCGGCGCTGCCGCCCCCGCCGCCCCCGGCCCGCGCCTTCGG
                 CCCGGGCCCCGCCGAGACCCCTGCCGTGGGGCCGGGCCCTGGGCCGCGGGCCGCGCTG
                 AGCCGCAGCGCCAGTGTGCGGTGCGCGGGCCCTGGCGGGGGCGGAGGCGGGGGCGCGC
                 CGGGCGCGCTCTGGACTGAGGCTCGCGAGCAGGCCCTATGCGGCCCCGGCCTGCGCAA
                 AACCAAGTACCGCAGCTTCCGCCGGCGGCTGCTCAAGTTCATCCCCGGACTCAACCGC
                 TCCCTGGAGGAGGAGGAGAGCCAGCTGTAGGGGCGGGGGCGGGCAGGGAGGTATTTAT
                 TTATTTATTCGCAACAGCCAGCGCTAAAA
                 ORF Start: ATG at 61 ORF Stop: TAG at 1246
                 SEQ ID NO:16         395 aa MW at 42622.9 kD
NOV8a,           MTLRRLRKLQQKEEAAATPDPAARTPDSEVAPAAPVPTPGPPAAAATPGPPADELYAA
CG102092-01      LEDYHPAELYRALAVSGGTLPRRKGSGFRWKNLSQSPEQQRKVLTLEKEDNQTFGFEI
Protein Sequence QTYGLHHREEQRVEMVTFVCRVHESSPAQLAGLTPGDTIASVNGLNVEGIRHREIVDI
                 IKASGNVLRLETLYGTSIRKAELEARLQYLKQTLYEKWGEYRSLMVQEQRLVHGLVVK
                 DPSIYDTLESVRSCLYGAGLLPGSLPFGPLLAVPGRPRGGARRARGDADDAVYHTCFF
                 GDSEPPALPPPPPPARAFGPGPAETPAVGPGPGPRAALSRSASVRCAGPGGGGGGGAP
                 GALWTEAREQALCGPGLRKTKYRSFRRRLLKFIPGLNRSLEEEESQL

[0341] Further analysis of the NOV8a protein yielded the following properties shown in Table 8B.

TABLE 8B
Protein Sequence Properties NOV8a
PSort     0.3600 probability located in mitochondrial matrix space;
analysis: 0.3000 probability located in microbody (peroxisome);
          0.3000 probability located in nucleus;
          0.2357 probability located in lysosome (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0342] 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.

TABLE 8C
Geneseq Results for NOV8a
		NOV8a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAU75901	Human modulator of GRIP-1 and	1 . . . 395	394/395 (99%)	0.0
	arf activity (MGAA) - Homo	1 . . . 395	395/395 (99%)
	sapiens, 395 aa. [WO200200714-
	A2, 03-JAN-2002]
ABG16389	Novel human diagnostic protein	3 . . . 176	118/189 (62%)	2e−50
	#16380 - Homo sapiens, 302 aa.	110 . . . 287	126/189 (66%)
	[WO200175067-A2, 11-OCT-2001]
ABG16389	Novel human diagnostic protein	3 . . . 176	118/189 (62%)	2e−50
	#16380 - Homo sapiens, 302 aa.	110 . . . 287	126/189 (66%)
	[WO200175067-A2, 11-OCT-2001]
AAB30608	Amino acid sequence of a human	71 . . . 394	129/333 (38%)	5e−47
	B3-1 polypeptide - Homo sapiens,	45 . . . 358	186/333 (55%)
	359 aa. [WO200075670-A1, 14-DEC-2000]
AAB58166	Lung cancer associated polypeptide	71 . . . 208	69/141 (48%)	2e−29
	sequence SEQ ID 504 - Homo	49 . . . 189	99/141 (69%)
	sapiens, 251 aa. [WO200055180-
	A2, 21-SEP-2000]

[0343] In a BLAST search of public sequence datbases, the NOV8a protein was found to have homology to the proteins shown in the BLASTP data in Table 8D.

TABLE 8D
Public BLASTP Results for NOV8a
		NOV8a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
CAD22389	SEQUENCE 1 FROM PATENT	1 . . . 395	394/395 (99%)	0.0
	WO0200714 - Homo sapiens	1 . . . 395	395/395 (99%)
	(Human), 395 aa.
AAL87038	TAMALIN - Rattus norvegicus	1 . . . 395	361/395 (91%)	0.0
	(Rat), 394 aa.	1 . . . 394	366/395 (92%)
Q9JKL0	GRP1-ASSOCIATED SCAFFOLD	1 . . . 395	358/395 (90%)	0.0
	PROTEIN GRASP - Mus musculus	1 . . . 392	365/395 (91%)
	(Mouse), 392 aa.
Q9JJA9	BRAIN CDNA, CLONE MNCB-	1 . . . 395	357/395 (90%)	0.0
	4428, SIMILAR TO MUS	1 . . . 392	364/395 (91%)
	MUSCULUS GRP1-ASSOCIATED
	SCAFFOLD PROTEIN GRASP
	MRNA - Mus musculus (Mouse),
	392 aa.
CAC22473	SEQUENCE 1 FROM PATENT	71 . . . 394	129/333 (38%)	1e−46
	WO0075670 - Homo sapiens	45 . . . 358	186/333 (55%)
	(Human), 359 aa.

[0344] PFam analysis predicts that the NOV8a protein contains the domains shown in the Table 8E.

TABLE 8E
Domain Analysis of NOV8a
		Identities/
Pfam	NOV8a	Similarities
Domain	Match Region	for the Matched Region	Expect Value
PDZ	101 . . . 189	30/92 (33%)	1.2e−10
		69/92 (75%)

Example 9

[0345] The NOV9 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 9A.

TABLE 9A
NOV9 Sequence Analysis
                 SEQ ID NO:17         3774 bp
NOV9a,           TGGTTTTTGGTTTTTTTCTTTGATCATTATGAACATTGGCTTTTCACCCCTGAAGTGA
CG102595-01      AAATGTTGAAAACTGAGTCTTCAGGTGAACGAACCACTCTCAGAAGTGCCTCTCCTCA
DNA Sequence     CAGGAATGCATATCGAACTGAGTTTCAGGCACTGAAAAGTACCTTTGACAAACCCAAG
                 TCAGATGGGGAACAAAAAACAAAAGAAGGTGAGGGCTCCCAGCAGAGCAGGGGGAGGA
                 AATATGGCTCCAATGTCAACAGAATTAAAAACCTATTTATGCAGATGGGTATGGAACC
                 CAACGAGAATGCTGCAGTCATTGCCAAAACAAGGGGGAAAGGTGGACATTCATCTCCT
                 CAGAGAAGAATGAAGCCCAAAGAATTTCTGGAAAAAACAGATGGCTCAGTTGTTAAGT
                 TGGAGTCTTCTGTTTCTGAACGAATTAGTAGATTTGACACTATGTACGATGGCCCTTC
                 ATATTCCAAGTTCACTGAGACTCGAAAGATGTTTGAGAGAAGTGTGCATGAATCAGGA
                 CAGAACAACCGCTATTCCCCAAAGAAAGAGAAAGCTGGAGGGAGTGAACCTCAGGATG
                 AATGGGGAGGTTCCAAGTCCAACAGAGGCAGTACTGATTCCTTGGACAGCCTTAGCTC
                 CCGAACTGAGGCTGTCTCCCCAACTGTGAGTCAACTGAGTGCAGTATTTGAGAACACT
                 GATTCTCCCAGTGCCATCATTTCTGAGAAGGCTGAAAACAATGAATACTCAGTGACTG
                 GGCATTATCCCTTGAATTTACCATCTGTTACTGTTACAAATCTTGACACATTTGGTCA
                 CCTGAAGGATTCTAATTCCTGGCCTCCTTCAAACAAGCGAGGTGTTGATACAGAGGAT
                 GCTCACAAGAGTAATGCAACTCCAGTACCAGAAGTGGCTTCTAAAAGTACCTCTCTAG
                 CTTCGATACCTGGTGAAGAGATCCAGCAGAGCAAGGAACCCGAGGACTCCACATCTAA
                 TCAACAGACTCCCGACAGCATTGACAAAGATGGTCCTGAAGAACCTTGTGCTGAAAGT
                 AAGGCAATGCCAAAGTCCGAAATCCCTTCACCACAAAGCCAACTGTTAGAAGATGCTG
                 AAGCTAATTTGGTTGGAAGGGAGGCAGCAAAGCAACAGAGGAAAGAACTTGCAGGTGG
                 TGATTTCACCTCTCCTGATGCTTCTGCATCCAGTTGTGGAAAAGAAGTACCTGAAGAT
                 TCAAATAATTTTGATGGTTCCCATGTGTACATGCACAGTGACTATAATGTGTATAGGG
                 TGAGATCCAGGTATAATTCAGACTGGGGAGAGACAGGCACTGAGCAGGATGAGGAGGA
                 AGATAGTGATGAGAACAGTTACTATCAGCCTGATATGGAGTACTCGGAAATTGTTGGA
                 TTGCCAGAAGAAGAAGAAATCCCAGCAAATAGGAAAATTAAGTTTAGTAGTGCTCCTA
                 TTAAGGTTTTCAACACATACTCCAATGAAGACTATGACAGGAGAAATGACGAAGTTGA
                 CCCTGTGGCTGCTTCAGCTGAGTATGAACTTGAAAAACGTGTAGAAAAGCTGGAACTT
                 TTCCCAGTGGAGCTAGAGAAAGATGAGGATGGTCTTGGTATAAGTATTATTGGAATGG
                 GTGTTGGAGCAGATGCTGGACTTGAAAAGCTGGGAATATTCGTCAAGACAGTAACAGA
                 AGGTGGTGCTGCTCAACGGGATGGCAGAATACAAGTCAATGACCAGATTGTGGAAGTG
                 GATGGAATCAGCTTGGTGGGTGTGACACAGAATTTTGCAGCAACAGTTCTCAGAAACA
                 CCAAGGGCAACGTCAGATTTGTTATTGGGCGGGAAAAACCAGGACAAGTGAGCGAGGT
                 TGCCCAGTTGATAAGCCAGACACTGGAACAGGAGAGGCGCCAGAGAGAGCTGCTGGAA
                 CAGCACTATGCCCAGTATGATGCCGACGATGACGAGACAGGAGAATATGCCACAGATG
                 AAGAAGAAGATGAGGTAGGACCTGTCCTTCCTGGCAGCGACATGGCCATTGAAGTCTT
                 TGAGCTGCCTGAGAATGAGGACATGTTTTCCCCATCAGAACTGGACACAAGCAAGCTC
                 AGTCACAAGTTCAAAGAGTTGCAAATCAAACATGCAGTTACAGAAGCAGAGATTCAAA
                 AATTGAAGACCAAGCTGCAGGCAGCAGAAAATGAGAAAGTGAGGTGGGAACTAGAAAA
                 AACCCAACTCCAACAAAACATAGAAGAGAATAAGGAAAGAATGTTGAAGTTGGAAAGC
                 TACTGGATTGAGGCCCAAACATTATGCCACACAGTGAATGAGCATCTCAAAGAGACTC
                 AAAGCCAGTATCAGGCCTTGGAAAAGAAATACAACAAGGCAAAGAAGTTGATCAAGGA
                 TTTTCAACAAAAAGAGCTTGATTTCATCAAAAGACAGGAAGCAGAAAGAAAGAAAATA
                 GAAGATTTGGAAAAAGCTCATCTTGTGGAAGTGCAAGGCCTCCAAGTGCGGATTAGAG
                 ATTTGGAAGCTGAGGTATTCAGGCTACTGAAGCAAAATGGGACTCAAGTTAACAATAA
                 TAACAACATCTTTGAGAGAAGAACATCTCTTGGTGAAGTCTCTAAAGGGGATACCATG
                 GAGAACTTGGATGGCAAGCAGACATCTTGCCAAGATGGCCTAAGTCAAGACTTGAATG
                 AAGCAGTCCCAGAGACAGAGCGCCTGGATTCAAAAGCACTGAAAACTCGAGCCCAGCT
                 CTCTGTGAAGAACAGACGCCAGAGACCCTCTAGGACAAGACTGTATGATAGTGTTAGT
                 TCCACAGATGGGGAGGACAGTCTAGAGAGAAAGAATTTTACCTTCAATGATGACTTCA
                 GTCCCAGCAGTACCAGTTCAGCAGACCTCAGCGGCTTAGGAGCAGAACCTAAAACACC
                 AGGGCTCTCTCAGTCCTTAGCACTGTCATCAGATGAGAGCCTGGATATGATAGATGAC
                 GAGATCCTTGATGATGGACAGTCTCCCAAACACAGTCAGTGTCAGAATCGGGCCGTTC
                 AGGAATGGAGTGTGCAGCAGGTTTCTCACTGGTTAATGAGCCTAAATCTGGAGCAGTA
                 TGTATCTGAATTCAGTGCCCAAAACATCACTGGAGAACAGCTCCTGCAGTTGGATGGA
                 AATAAACTTAAGGCTCTTGGAATGACAGCATCCCAGGACCGAGCAGTGGTCAAAAAGA
                 AACTCAAGGAAATGAAGATGTCTCTAGAGAAGGCTCGGAAGGCCCAAGAGAAAATGGA
                 AAAACAAAGAGAAAAGCTAAGGAGAAAGGAGCAAGAGCAAATGCAGAGGAAGTCCAAA
                 AAGACAGAAAAGATGACGTCAACTACAGCCGAGGGTGCTGGTGAGCAGTAACACATAC
                 CCTCTTACAGATGATGGAGATGCTCCAAGAGAAGTCCCCACCTCTTCCTGCCCTGCTC
                 TCCTCCAGAGGATGAAAAAGAAACTAAATGATAAGGGTAATGCGGCTCTAGGCCGGCT
                 GAGGAACTGTGTGTTGAATAACTGCATTTTCTGCAATAGAATGCACTCTTAATTTTAA
                 CTACTAAAATAATCCCAAGCCACCTTTGGTTCATTAACAAACCAGAGATTTCATTTAA
                 GTAGCTGTGTTTTGCTCTTCTCTAACTTACCAACATCTTGTGTTGTGTTGGGTGTGTT
                 TTGTCACTTGGAGAACTAGTGTGACCCCACCCAAGAGCATGACACACCCTGGTGTTGT
                 TAATGGAGCGCCGTGAATTTTCAGTGTGGGATCCTGAAATGGCAATTGCACATGTCTG
                 CATG
                 ORF Start: ATG at 61 ORF Stop: TAA at 3355
                 SEQ ID NO:18         1098 aa MW at 123340.9 kD
NOV9a,           MLKTESSGERTTLRSASPHRNAYRTEFQALKSTFDKPKSDGEQKTKEGEGSQQSRGRK
CG102595-01      YGSNVNRIKNLFMQMGMEPNENAAVIAKTRGKGGHSSPQRRMKPKEFLEKTDGSVVKL
Protein Sequence ESSVSERISRFDTMYDGPSYSKFTETRKMFERSVHESGQNNRYSPKKEKAGGSEPQDE
                 WGGSKSNRGSTDSLDSLSSRTEAVSPTVSQLSAVFENTDSPSAIISEKAENNEYSVTG
                 HYPLNLPSVTVTNLDTFGHLKDSNSWPPSNKRGVDTEDAHKSNATPVPEVASKSTSLA
                 SIPGEEIQQSKEPEDSTSNQQTPDSIDKDGPEEPCAESKAMPKSEIPSPQSQLLEDAE
                 ANLVGREAAKQQRKELAGGDFTSPDASASSCGKEVPEDSNNFDGSHVYMHSDYNVYRV
                 RSRYNSDWGETGTEQDEEEDSDENSYYQPDMEYSEIVGLPEEEEIPANRKIKFSSAPI
                 KVFNTYSNEDYDRRNDEVDPVAASAEYELEKRVEKLELFPVELEKDEDGLGISIIGMG
                 VGADAGLEKLGIFVKTVTEGGAAQRDGRIQVNDQIVEVDGISLVGVTQNFAATVLRNT
                 KGNVRFVIGREKPGQVSEVAQLISQTLEQERRQRELLEQHYAQYDADDDETGEYATDE
                 EEDEVGPVLPGSDMAIEVFELPENEDMFSPSELDTSKLSHKFKELQIKHAVTEAEIQK
                 LKTKLQAAENEKVRWELEKTQLQQNIEENKERMLKLESYWIEAQTLCHTVNEHLKETQ
                 SQYQALEKKYNKAKKLIKDFQQKELDFIKRQEAERKKIEDLEKAHLVEVQGLQVRIRD
                 LEAEVFRLLKQNGTQVNNNNNIFERRTSLGEVSKGDTMENLDGKQTSCQDGLSQDLNE
                 PSSTSSADLSGLGAEPKTPGLSQSLALSSDESLDMIDDEILDDGQSPKHSQCQNRAVQ
                 EWSVQQVSHWLMSLNLEQYVSEFSAQNITGEQLLQLDGNKLKALGMTASQDRAVVKKK
                 LKEMKMSLEKARKAQEKMEKQREKLRRKEQEQMQRKSKKTEKMTSTTAEGAGEQ

[0346] Further analysis of the NOV9a protein yielded the following properties shown in Table 9B.

TABLE 9B
Protein Sequence Properties NOV9a
PSort     0.8800 probability located in nucleus; 0.4472 probability
analysis: located in mitochondrial matrix space; 0.3000 probability
          located in microbody (peroxisome); 0.1362 probability located
          in mitochondrial inner membrane
SignalP   No Known Signal Sequence Predicted
analysis:

[0347] 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 9C.

TABLE 9C
Geneseq Results for NOV9a
		NOV9a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAW80359	An F-actin-combined protein	1 . . . 1093	984/1094 (89%)	0.0
	amino acid sequence - Rattus sp,	1 . . . 1094	1032/1094 (93%)
	1095 aa. [JP10276784-A, 20-OCT-1998]
AAU00022	Human activated T-lymphocyte	1 . . . 829	385/876 (43%)	e−173
	associated sequence 1, ATLAS-1 -	1 . . . 783	500/876 (56%)
	Homo sapiens, 862 aa.
	[WO200114564-A2, 01-MAR-2001]
AAB42620	Human ORFX ORF2384	415 . . . 817	276/403 (68%)	e−157
	polypeptide sequence SEQ ID	54 . . . 455	333/403 (82%)
	NO: 4768 - Homo sapiens, 460 aa.
	[WO200058473-A2, 05-OCT-2000]
AAB36879	Murine Bau protein - Mus sp, 293	665 . . . 924	243/260 (93%)	e−135
	aa. [US6140465-A, 31-OCT-2000]	1 . . . 260	251/260 (96%)
AAW44873	Murine BIN-1 Associated U1	665 . . . 924	243/260 (93%)	e−135
	specific protein - Mus sp, 293 aa.	1 . . . 260	251/260 (96%)
	[WO9808866-A1, 05-MAR-1998]

[0348] In a BLAST search of public sequence datbases, the NOV9a protein was found to have homology to the proteins shown in the BLASTP data in Table 9D.

TABLE 9D
Public BLASTP Results for NOV9a
		NOV9a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
O35867	Neurabin-I (Neural tissue-specific	1 . . . 1093	985/1094 (90%)	0.0
	F-actin binding protein I) (Protein	1 . . . 1094	1033/1094 (94%)
	phosphatase 1 regulatory subunit
	9A) (p180) (PP1bp175) - Rattus
	norvegicus (Rat), 1095 aa.
Q9ULJ8	Neurabin-I (Neural tissue-specific	357 . . . 1098	742/742 (100%)	0.0
	F-actin binding protein I) (Protein	1 . . . 742	742/742 (100%)
	phosphatase 1 regulatory subunit
	9A) - Homo sapiens (Human), 742
	aa (fragment).
O35274	Neurabin-II (Neural tissue-specific	1 . . . 826	411/862 (47%)	0.0
	F-actin binding protein II) (Protein	1 . . . 817	516/862 (59%)
	phosphatase 1 regulatory subunit
	9B) (Spinophilin) (p130)
	(PP1bp134) - Rattus norvegicus
	(Rat), 817 aa.
Q96SB3	NEURABIN II PROTEIN - Homo	1 . . . 826	403/865 (46%)	0.0
	sapiens (Human), 817 aa.	1 . . . 817	524/865 (59%)
CAD28455	HYPOTHETICAL 47.0 KDA	415 . . . 826	279/412 (67%)	e−157
	PROTEIN - Homo sapiens	1 . . . 411	336/412 (80%)
	(Human), 411 aa (fragment).

[0349] PFam analysis predicts that the NOV9a protein contains the domains shown in the Table 9E.

TABLE 9E
Domain Analysis of NOV9a
		Identities/
Pfam	NOV9a	Similarities
Domain	Match Region	for the Matched Region	Expect Value
PDZ	504 . . . 591	27/91 (30%)	1.5e−15
		69/91 (76%)
SAM	986 . . . 1049	22/68 (32%)	1e−12
		47/68 (69%)

Example 10

[0350] The NOV10 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 10A.

TABLE 10A
NOV10 Sequence Analysis
                 SEQ ID NO:19        435 bp
NOV10a,          CCCACCATGGCCACAGTTCAGCAGCTGGAAGGAAGATGGCGCCTGGTGGACAGCGAAG
CG102744-01      GCTTTGATGAATACATGAAGGAGCTAGGAGGAATAGCTTTGCAAAAAATGGGCGCAAT
DNA Sequence     GGCCAAGCCAGATTGTATCATCACTTGTGATGGCAAAAACCTCACCATAAAAACTGAG
                 AGCACTTTGAAAACAACACAGTTTTCTTGTACCCTGGGAGAGAAGTTTGAAGAAACCA
                 CAGCTGATGGCAGAAAAACTCAGACTGTGTGCAACTTTACAGATGGTGCATTGGTTCA
                 GCATCAGGAGTGGGATGGGAAGGAAAGCACAATAACAAGAACATTGAAAGATGGGAAA
                 TTAGTGGTGGACTGTGTCATGAACCATGTCGCCTGTACTCGGATCTATGAAAAAGTAC
                 AATAAAGATTCCATCATCACTTTGGACAG
                 ORF Start: ATG at 7 ORF Stop: TAA at 409
                 SEQ ID NO:20        134 aa MW at 14989.0 kD
NOV10a,          MATVQQLEGRWRLVDSEGFDEYMKELGGIALQKMGAMAKPDCIITCDGKNLTIKTEST
CG102744-01      LKTTQFSCTLGEKFEETTADGRKTQTVCNFTDGALVQHQEWDGKESTITRTLKDGKLV
Protein Sequence VDCVMNHVACTRIYEKVQ

[0351] Further analysis of the NOV10a protein yielded the following properties shown in Table 10B.

TABLE 10B
Protein Sequence Properties NOV10a
PSort     0.6500 probability located in cytoplasm; 0.1000 probability
analysis: located in mitochondrial matrix space;
          0.1000 probability located in lysosome (lumen); 0.0000
          probability located in endoplasmic reticulum (membrane)
SignalP   No Known Signal Sequence Predicted
analysis:

[0352] 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 10C.

TABLE 10C
Geneseq Results for NOV10a
		NOV10a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAU08674	Human keratinocyte fatty acid	1 . . . 134	127/135 (94%)	4e−70
	binding protein, Mal1 - Homo	1 . . . 135	132/135 (97%)
	sapiens, 135 aa. [WO200160384-
	A1, 23-AUG-2001]
AAR55866	Melanogenic inhibitor - Homo	1 . . . 134	127/135 (94%)	4e−70
	sapiens, 135 aa. [WO9412534-A,	1 . . . 135	132/135 (97%)
	09-JUN-1994]
ABG27577	Novel human diagnostic protein	1 . . . 134	125/135 (92%)	9e−69
	#27568 - Homo sapiens, 158 aa.	24 . . . 158	130/135 (95%)
	[WO200175067-A2, 11-OCT-2001]
ABG27577	Novel human diagnostic protein	1 . . . 134	125/135 (92%)	9e−69
	#27568 - Homo sapiens, 158 aa.	24 . . . 158	130/135 (95%)
	[WO200175067-A2, 11-OCT-2001]
AAU08666	Human NOV10 protein - Homo	1 . . . 134	114/135 (84%)	1e−60
	sapiens, 134 aa. [WO200168851-	1 . . . 134	122/135 (89%)
	A2, 20-SEP-2001]

[0353] In a BLAST search of public sequence datbases, the NOV10a protein was found to have homology to the proteins shown in the BLASTP data in Table 10D.

TABLE 10D
Public BLASTP Results for NOV10a
		NOV10a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q01469	Fatty acid-binding protein, epidermal	1 . . . 134	127/135 (94%)	9e−70
	(E-FABP) (Psoriasis-associated fatty	1 . . . 135	132/135 (97%)
	acid-binding protein homolog) (PA-
	FABP) - Homo sapiens (Human),
	135 aa.
P55052	Fatty acid-binding protein, epidermal	1 . . . 134	117/135 (86%)	8e−64
	(E-FABP) (Differentiation-	1 . . . 135	128/135 (94%)
	associated lipid binding protein LP2) -
	Bos taurus (Bovine), 135 aa.
P55053	Fatty acid-binding protein, epidermal	1 . . . 134	106/135 (78%)	6e−60
	(E-FABP) (Cutaneous fatty acid-	1 . . . 135	125/135 (92%)
	binding protein) (C-FABP) (DA11) -
	Rattus norvegicus (Rat), 135 aa.
Q05816	Fatty acid-binding protein, epidermal	1 . . . 134	103/135 (76%)	2e−59
	(E-FABP) (Psoriasis-associated fatty	1 . . . 135	123/135 (90%)
	acid-binding protein homolog) (PA-
	FABP) (Keratinocyte lipid- binding
	protein) - Mus musculus (Mouse),
	135 aa.
MPRB2	myelin P2 protein - rabbit, 132 aa.	9 . . . 133	74/126 (58%)	9e−36
		7 . . . 132	94/126 (73%)

[0354] PFam analysis predicts that the NOV10a protein contains the domains shown in the Table 10E.

TABLE 10E
Domain Analysis of NOV10a
	NOV10a	Identities/Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
lipocalin	6 . . . 133	38/157 (24%)	8.9e−26
		100/157 (64%)

Example 11

[0355] The NOV11 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 11A.

TABLE 11A
NOV11 Sequence Analysis
                 SEQ ID NO:21         4702 bp
NOV11a,          CTCCTCTGTTTCCTGTGCAGTAGCTCCCGTTGCGGCGGCACCCGTGGCAGCCCTGGCG
CG102801-01      GACGCAGGAGCGATGGCAGCGACCGATATAGCTCGCCAGGTGGGTGAAGGTTGCCGAA
DNA Sequence     CTGTCCCCCTGGCTGGACATGTGGGGTTTGACAGCTTGCCTGACCAGCTGGTGAATAA
                 GTCCGTCAGCCAGGGCTTCTGCTTCAACATCCTGTGCGTGGGAGAGACAGGTTTGGGC
                 AAGTCCACCCTCATGGACACCCTGTTCAACACCAAATTCGAAGGGGAGCCAGCCACCC
                 ACACACAGCCGGGTGTCCAGCTCCAGTCTAATACCTATGACCTCCAAGAGAGCAACGT
                 GAGGCTAAAGCTCACGATCGTTAGCACAGTTGGCTTTGGGGACCAGATCAACAAAGAG
                 GACAGCTACAAGCCTATCGTGGAATTCATCGATGCACAATTCGAGGCCTACCTGCAGG
                 AAGAGCTAAAGATCCGAAGAGTGCTACACACCTACCATGACTCCCGAATCCATGTCTG
                 CTTGTATTTCATTGCCCCCACGGGTCATTCCCTGAAGTCTCTGGACCTAGTGACTATG
                 AAGAAGCTGGACAGTAAGGTGAACATCATCCCCATCATTGCCAAAGCAGATGCCATTT
                 CGAAGAGTGAGCTAACAAAGTTCAAAATCAAAATCACCAGCGAGCTTGTCAGCAACGG
                 AGTCCAGATCTATCAGTTTCCTACAGATGATGAGTCGGTGGCAGAGATCAATGGAACC
                 ATGAACGCCCACCTGCCGTTTGCTGTCATTGGCAGCACAGAAGAACTGAAGATAGGCA
                 ACAAGATGATGAGGGCGCGGCAGTATCCTTGGGGCACTGTGCAGGTTGAAAACGAGGC
                 CCACTGCGACTTTGTGAAGCTGCGGGAGATGCTGATTCGGGTCAACATGGAGGATCTG
                 CGGGAGCAGACCCACACCCGGCACTATGAGCTGTATCGCCGCTGTAAGCTGGAGGAGA
                 TGGGCTTCAAGGACACCGACCCTGACAGCAAACCCTTCAGTTTACAGGAGACATATGA
                 GGCCAAAAGGAACGAGTTCCTAGGGGAACTCCAGAAAAAAGAAGAGGAGATGAGACAG
                 ATGTTCGTCCAGCGAGTCAAAGAGAAAGAAGCGGAGCTCAAAGAGGCAGAGAAAGAGC
                 TGCACGAGAAGTTTGACCGTCTGAAGAAACTGCACCAGGACGAGAAGAAGAAACTGGA
                 GGATAAGAAGAAATCCCTGGATGATGAAGTGAATGCTTTCAAGCAAAGAAAGACGGCG
                 GCTGAGCTGCTCCAGTCCCAGGGCTCCCAGGCTGGAGGCTCACAGACTCTGAAGAGAG
                 ACAAAGAGAAGAAAAATTAACTCTGCTGTTTGCTGCATGCTGCATGAGACCCAGGGTC
                 CTGTTTGGGCTTCCTGTAGACACCCTTTTCCTGCGCAACAGAGCTGGGCCTCCCTTTC
                 TCTAATTTCCCCCTTAACATGCCTGGGGGGCATACAATCCAACCCGCGCCCTCTCCTC
                 TCTTCCTGCCAAGGTTTATAGAAACCTGAGAATCTGAGGGTGATGTCTGGCCGCTGGT
                 CAAGAAGCCAACAGTCATGTGGCTCGCAGATGCATCCTGCATCCCAGTCCCCCTCCCA
                 GCACCCCCAGCCATCCCCCCTGTCTTCCCCCACATCTTTGCCAGAGGTGTGACATGGT
                 CAGGGGGCCCATCTGCTACTCTTTCCCACCAGCTCCCCTGTTCCAGTTCTGGTTGCTG
                 TTAGTTTCCCTGAGGTATTTGCAACCACCATGGCTGGGTAACCACCGATCAGCACAGC
                 TGTCCCCTTGGTCTCCTGTATCCCAGTCACTAGTCCTCCCTGGTCCACCCCACCCTCA
                 TCCTCAGGAGCCACAGCCATTTCTTAGAGGGTTTCAAAAGGACAGCCTTTGGCGCCTT
                 TTCCTTCTAACCTTTGAGTCCAGCCCTTTCCAGTTTTCATTCACTCGAAGTAACTGCA
                 CTCAAGCTGTGCTCAAAATCGGCAACGCATTTATTTACACCAAGCCCTTCCCATAAAA
                 CACAACTGCTGAAGAAAATAGCAGACGTTTCCCCTCTCTCTAACTCTGGGTATCCCAC
                 AGATGCAAAAGGGAGAATAAACCTGAATATTATTACCAGCCTAGAGTCTTGAATGATA
                 GCCTTACCGAATTCTTCTTGTGAGGTATTTCAGCATCTCGGGGGGTAATTTCCGGAAG
                 GGCTCCATACTGTCCCAATAAGGTGAGGCCAGTAGCAGGAATAATAAATCCCACTTTG
                 TAGGCTGGAAAACTGAGCTGTCAAAAGAATCAAGTGTTTGGGGGTTTGCTCTGATGAG
                 TCTTCTAGTTCATTTGGTGAATGTCATGATGATTTTTAACATGCATTTTGCATGCATC
                 CCCCAATAAGAAGAGATGAGACTCGGCCGGAGAGAAGAAAAGGCCCTTAACTTTCTTT
                 CCAATTTAAGGAGTTGAGAGTTTAAAAATATTCCAGCCCTAAGTTTTTATCATGGGTC
                 CCATCTGATAGTGGCTTTGGGAACCTCTGTGAAGTAGAGAGCCCTCCCTTGTCAGGGT
                 TATGAGGCACAGTGGCCTTTGGTGTTTGGCCAGTGACAGTGTGAGAGATGGAGTTGAC
                 CTGGCAATGATCTGTGGCTAACATGCCGTCTCTCTGCCCTTCCTTTGCAGTAATCCAT
                 GGCTGTGTACTGAATAGTATTCCCCGCTACAGCTGGACTGGACTCCATTTAGCCTTTT
                 AAGCCGAGGTTCCTATTTTAACTGACAGCTTTCCTTTGGGGTGCCAGGCAGCGAGGCC
                 CCCCACCCCTATCCTGCCATGTACTTCAAGCTCACTTCTTCTTTTTGAGTTCCGCAAC
                 TTGCTCCTGCCTCCCAGCCCCACTGGCACTGACCATGACCACCTACTTCTATTTTTTT
                 TTTAGAGTTTCTTTTTTTGATCACTTACTTTCAAAGCACACAGTCAAACAAGGTTATG
                 CCAAATTTCCAGGCCTTTTTGAAGTATTGAGAAGGGGAAGGGGATTTCTCACTTCAAT
                 TATAGATCATAATAGGAAGCAAAAAGAAAAAAATGAAAAGCAAACATATGCACGCACT
                 TTTCTTGTTGACAAAGCAAGAATGTAGGTTTGCTGTGTAGGTTTGGTGCTCTATTGAT
                 TGGTGAGTGACCAGAGCAAGTATGAAGGTGATGCTGCCAAAGCACAAGCCTTTTTGAA
                 GTATTGAGAAGGGGAAGGGGATTTCTCACTTCAATTATAGATCATAATAGGAAGCAAA
                 AAGAAAAAAATGAAAAGCAAACATATGCACGCACTTTTCTTGTTGACAAAGCAAGAAT
                 ATAGGTTTGCTGTGTAGGTTTGGTGCTCTATTGATTGGTGAGTGACCAGAGCAAGTAT
                 GAAGGTGATGCTGCCAAAGCACAAGCCAGTTTCTTGGGAAAATTCAAGTTACAGTGGA
                 GTATTTTTTTGAAGACCATATGCTTGGAGGTAGAAACAAACCAACGACCAAAAAAAAA
                 AAAAAAAAAAAAATCTGCTCAGATACTCAGCCAGTAGCTCAGAGAGATGCTGAGTTAG
                 GCCTGTCAGGTCTCCTTGGGAAAGGCTTCATATTTGCAACTTTGATGATTCTATGTCC
                 AGCTTCAGAGCTGCTTTCCCAGAAATTCACGCTTAAACAACCAACCGGTAACCACCAC
                 TTCCCCACACCGCCGCCCGGTAATTATTTGCATTACAAACCGGAGGCGCCCTCATTTG
                 CATTTGTGTACAGATTAACTAGTTAAGGCTTGAGAAGCTCTGAATAATTCAAAAGTAT
                 TAGACCCACACAGCCTTGGAGAGACCTTCAGAAACTAAGGAGGAGTTTTATATTAAGG
                 GAGACATTTTAGTCAGTAAGACGATATAACCTACTTACTCCGTAAGGGGAAATGAAGG
                 CCCGGAGAAGGGAAGGGACTTGACCGAGGTCCCACTTCTGTTTCGAGGCAGAAGCCAG
                 ACTAATTTTCATGCCTCCTGACTCCCAATCAGTTTCACAAAGGGATTCAATCTGTTTA
                 TATACGTTACATTCCTGGATACGAGGTCTTTTGATGTTCAGAGTAACTGACTAGTTAG
                 TATTAGAAGACCCTCGAGGTTTTTTTCCACAGAAAAACATCTGAAGATGGATTGGGTG
                 AGGGCTGGCAAAACGAAGGCATGCCGGGCCAGCTCCTTAACCCAATGACCCAGTGATG
                 CTGCAAGGCTGGAACGGGGTCCAGGAGACTGTGTGTAACAGGTGCCCTAGGTGACCCT
                 TATAATCAGGGAAGTTTGGTGAACAAAAATCGAACCCATGAGTGAACATAAATTAAAA
                 AGTTGATCAACCTATTAAAATGTGTATTTCATTGGGTAGCTTTTCTCACTGTAGACAG
                 ATTTTTTCCTTCTTCAATGAAAAGGCTTTTAAATTAGTACAACTGTTACTATTTAAAA
                 AAAAAATACCCTAAGTACTCTGTTTACTTCTGGTGAAACAAAACCAGTCATTAGAAAT
                 GGTCTGTGCTTTTATTTTCCCAGACTGGAGTGGCTTTTCTGAAACACACACACACACA
                 CACACACACACACACACACACACACACGTACACACATCCCTCACTTCTCTTAAGCCAA
                 GAAGTTTGCTTTCCCTAGCTGCAGTGTAGATGGCTCTTGTTTTTGTTTTTTTGTTTTA
                 ATCATTTGGCATTCACATGTGGCTGTTAATATGTGCTTGTTTTTAATTAAAACAAGAA
                 GCTT
                 ORF Start: ATG at 71 ORF Stop: TAA at 1352
                 SEQ ID NO:22         427 aa MW at 48872.3 kD
NOV11a,          MAATDIARQVGEGCRTVPLAGHVGFDSLPDQLVNKSVSQGFCFNILCVGETGLGKSTL
CG102801-01      MDTLFNTKFEGEPATHTQPGVQLQSNTYDLQESNVRLKLTIVSTVGFGDQINKEDSYK
Protein Sequence PIVEFIDAQFEAYLQEELKIRRVLHTYHDSRIHVCLYFIAPTGHSLKSLDLVTMKKLD
                 SKVNIIPIIAKADAISKSELTKFKIKITSELVSNGVQIYQFPTDDESVAEINGTMNAH
                 LPFAVIGSTEELKIGNKMMRARQYPWGTVQVENEAHCDFVKLREMLIRVNMEDLREQT
                 HTRHYELYRRCKLEEMGFKDTDPDSKPFSLQETYEAKRNEFLGELQKKEEEMRQMFVQ
                 RVKEKEAELKEAEKELHEKFDRLKKLHQDEKKKLEDKKKSLDDEVNAFKQRKTAAELL
                 QSQGSQAGGSQTLKRDKEKKN

[0356] Further analysis of the NOV11a protein yielded the following properties shown in Table 11B.

TABLE 11B
Protein Sequence Properties NOV11a
PSort     0.8800 probability located in nucleus; 0.3000 probability
analysis: located in microbody (peroxisome); 0.1000 probability
          located in mitochondrial matrix space; 0.1000 probability
          located in lysosome (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0357] 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 11C.

TABLE 11C
Geneseq Results for NOV11a
		NOV11a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAU21726	Novel human neoplastic disease	1 . . . 427	427/427 (100%)	0.0
	associated polypeptide #159 -	24 . . . 450	427/427 (100%)
	Homo sapiens, 452 aa.
	[WO200155163-A1, 02-AUG-2001]
AAU21837	Novel human neoplastic disease	1 . . . 426	426/426 (100%)	0.0
	associated polypeptide #270 -	52 . . . 477	426/426 (100%)
	Homo sapiens, 478 aa.
	[WO200155163-A1, 02-AUG-2001]
AAU18541	Human cytoskeletal element-	1 . . . 426	426/426 (100%)	0.0
	related polypeptide #34 - Homo	52 . . . 477	426/426 (100%)
	sapiens, 478 aa. [WO200155168-
	A1, 02-AUG-2001]
AAB93251	Human protein sequence SEQ ID	3 . . . 427	351/425 (82%)	0.0
	NO: 12267 - Homo sapiens, 429 aa.	2 . . . 425	386/425 (90%)
	[EP1074617-A2, 07-FEB-2001]
AAB23260	Human cell division regulator	3 . . . 427	351/425 (82%)	0.0
	HCDR-2 - Homo sapiens, 425 aa.	2 . . . 425	386/425 (90%)
	[US6121019-A, 19-SEP-2000]

[0358] In a BLAST search of public sequence datbases, the NOV11a protein was found to have homology to the proteins shown in the BLASTP data in Table 11D.

TABLE 11D
Public BLASTP Results for NOV11a
			Identities/
Protein		NOV11a Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q96A13	SEPTIN6 TYPE V (SEPTIN 2) -	1 . . . 427	427/427 (100%)	0.0
	Homo sapiens (Human), 429	1 . . . 427	427/427 (100%)
	aa.
Q969W5	SEPTIN6 TYPE III - Homo	1 . . . 427	427/427 (100%)	0.0
	sapiens (Human), 427 aa.	1 . . . 427	427/427 (100%)
Q14141	Septin 6 - Homo sapiens	1 . . . 427	427/427 (100%)	0.0
	(Human), 434 aa.	1 . . . 427	427/427 (100%)
Q96GR1	SIMILAR TO SEPTIN 6 -	1 . . . 427	426/427 (99%)	0.0
	Homo sapiens (Human), 434 aa.	1 . . . 427	426/427 (99%)
Q91XH2	SEPTIN 6 - Mus musculus	1 . . . 427	411/427 (96%)	0.0
	(Mouse), 427 aa.	1 . . . 427	420/427 (98%)

[0359] PFam analysis predicts that the NOV11a protein contains the domains shown in the Table 11E.

TABLE 11E
Domain Analysis of NOV11a
	NOV11a	Identities/Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
GTP_CDC	39 . . . 312	123/294 (42%)	8.4e−113
		210/294 (71%)

Example 12

[0360] The NOV12 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 12A.

TABLE 12A
NOV12 Sequence Analysis
                 SEQ ID NO:23         4140 bp
NOV12a,          GCCGCCGCTGCCAGTGGAGTTGCCTCCCCGCTTCCCTAGGGTGGTTCGGCTCCACCAA
CG102899-01      ACATGTCGGCTCCTGTCGGGCCCCGGGGCCGCCTGGCTCCCATCCCGGCGGCCTCTCA
DNA Sequence     GCCGCCTCTGCAGCCCGAGATGCCTGACCTCAGCCACCTCACGGAGGAGGAGAGGAAA
                 ATCATCCTGGCCGTCATGGATAGGCAGAAGAAAGAAGAGGAGAAGGAGCAGTCCGTGC
                 TCAAAAAACTGCATCAGCAGTTTGAAATGTATAAAGAGCAGGTAAAGAAGATGGGAGA
                 AGAATCACAGCAACAGCAAGAACAGAAGGGTGATGCGCCAACCTGTGGTATCTGCCAC
                 AAAACAAAGTTTGCTGATGGATGTGGCCATAACTGTTCATATTGCCAAACAAAGTTCT
                 GTGCTCGTTGTGGAGGTCGAGTGTCATTACGCTCAAACAAGGTTATGTGGGTATGTAA
                 TTTGTGCCGAAAACAACAAGAAATCCTCACTAAATCAGGAGCATGGTTTTATAATAGT
                 GGATCTAATACACCACAGCAACCTGATCAAAAGGTTCTTCGAGGGCTAAGAAATGAGG
                 AGGCACCTCAGGAGAAGAAACCAAAACTACATGAGCAGACCCAGTTCCAAGGACCCTC
                 AGGTGACTTATCTGTACCTGCAGTGGAGAAAAGTCGATCTCATGGGCTCACAAGACAG
                 CATTCTATTAAAAATGGGTCAGGCGTGAAGCATCACATTGCCAGTGACATAGCTTCAG
                 ACAGGAAAAGAAGCCCATCTGTGTCCAGAGATCAGAATAGAAGATACGACCAAAGGGA
                 AGAAAGAGAGGAATATTCACAGTATGCTACTTCGGATACCGCAATGCCTAGATCTCCA
                 TCAGATTATGCTGATAGGCGATCTCAACATGAACCTCAGTTTTATGAAGACTCTGATC
                 ATTTAAGTTATAGGGACTCCAACAGGAGAAGTCATAGGCATTCCAAAGAATATATTGT
                 AGATGATGAGGATGTGGAAAGCAGAGATGAATACGAAAGGCAAAGGAGAGAGGAAGAG
                 TACCAGTCACGCTACCGAAGTGATCCGAATTTGGCCCGTTATCCAGTAAAGCCACAAC
                 CCTATGAAGAACAAATGCGGATCCATGCTGAAGTGTCCCGAGCACGGCATGAGAGAAG
                 GCATAGTGATGTTTCTTTGGCAAATGCTGATCTGGAAGATTCCAGGATTTCTATGCTA
                 AGGATGGATCGACCATCAAGGCAAAGATCTATATCAGAACGTAGAGCTGCCATGGAAA
                 ATCAGCGATCTTATTCAATGGAAAGAACTCGAGAGGCTCAGGGACCAAGTTCTTATGC
                 ACAAAGGACCACAAACCATAGTCCTCCTACCCCCAGGAGGAGTCCACTACCCATAGAT
                 AGACCAGACTTGAGGCGTACTGACTCACTACGGAAACAGCACCACTTAGATCCTAGCT
                 CTGCTGTAAGAAAAACAAAACGGGAAAAAATGGAAACAATGTTAAGGAATGATTCTCT
                 CAGTTCAGACCAGTCAGAGTCAGTGAGACCTCCACCACCAAAGCCTCATAAATCAAAG
                 AAAGGCGGTAAAATGCGCCAGATTTCGTTGAGCAGTTCAGAGGAGGAATTGGCTTCCA
                 CGCCTGAATATACAAGTTGTGATGATGTTGAGATTGAAAGTGAGAGTGTAAGTGAAAA
                 AGGAGACATGGATTACAACTGGTTGGATCATACGTCTTGGCATAGCAGTGAGGCATCC
                 CCAATGTCTTTGCACCCTGTAACCTGGCAACCATCTAAAGATGGAGATCGTTTAATTG
                 GTCGCATTTTATTAAATAAGCGTCTAAAAGATGGAAGTGTACCTCGAGATTCAGGAGC
                 AATGCTTGGCTTGAAGGTTGTAGGAGGAAAGATGACTGAATCAGGTCGGCTTTGTGCA
                 TTTATTACTAAAGTAAAAAAAGGAAGTTTAGCTGATACTGTAGGACATCTTAGACCAG
                 GTGATGAAGTATTAGAATGGAATGGAAGACTACTGCAAGGAGCCACATTTGAGGAAGT
                 GTACAACATCATTCTAGAATCCAAACCTGAACCACAAGTAGAACTTGTAGTTTCAAGG
                 CCTATTGGAGATATACCGCGAATACCTGATAGCACACATGCACAACTGGAGTCCAGTT
                 CTAGCTCCTTTGAATCTCAAAAAATGGATCGTCCTTCTATTTCTGTTACCTCTCCCAT
                 GAGTCCTGGAATGTTGAGGGATGTCCCACAGTTCTTATCAGGACAACTTTCAATAAAA
                 CTATGGTTTGACAAGGTTGGTCACCAATTAATAGTTACAATTTTGGGAGCAAAAGATC
                 TCCCTTCCAGGGAAGATGGGAGGCCAAGGAATCCTTATGTTAAAATTTACTTTCTTCC
                 AGACAGAAGTGATAAAAACAAGAGAAGAACTAAAACAGTAAAGAAAACATTGGAACCC
                 AAATGGAACCAAACATTCATTTATTCTCCAGTCCACCGAAGAGAATTTCGGGAACGAA
                 TGCTAGAGATTACCCTTTGGGATCAAGCTCGTGTTCGAGAGGAAGAAAGTGAATTCTT
                 AGGCGAGATTTTAATTGAATTAGAAACAGCATTATTAGATGATGAGCCACATTGGTAC
                 AAACTTCAGACGCATGATGTCTCTTCATTGCCACTTCCCCACCCTTCTCCATATATGC
                 CACGAAGACAGCTCCATGGAGAGAGCCCAACACGGAGGTTGCAAAGGTCAAAGAGAAT
                 AAGTGATAGTGAAGTCTCTGACTATGACTGTGATGATGGAATTGGTGTAGTATCAGAT
                 TATCGACATGATGGTCGAGATCTTCAAAGCTCAACATTATCAGTGCCAGAACAAGTAA
                 TGTCATCAAACCACTGTTCACCATCAGGGTCTCCTCATCGAGTAGATGTTATAGGAAG
                 GACTAGATCATGGTCACCCAGTGTCCCTCCTCCACAAAGTCGGAATGTGGAACAGGGG
                 CTTCGAGGGACCCGCACTATGACCGGACATTATAATACAATTAGCCGAATGGACAGAC
                 ATCGTGTCATGGATGACCATTATTCTCCAGATAGAGACAGGGATTGTGAAGCAGCAGA
                 TAGACAGCCATATCACAGATCCAGATCAACAGAACAACGGCCTCTCCTTGAGCGGACC
                 ACCACCCGCTCCAGATCCACTGAACGTCCTGATACAAACCTCATGAGGTCGATGCCTT
                 CATTAATGACTGGAAGATCTGCCCCTCCTTCACCTGCCTTATCGAGGTCTCATCCTCG
                 TACTGGGTCTGTCCAGACAAGCCCATCAAGTACTCCAGTCGCAGGACGAAGGGGCCGA
                 CAGCTTCCACAGCTTCCACCAAAGGGAACGTTGGATAGAAAAGCAGGAGGTAAAAAAC
                 TAAGGAGCACTGTCCAAAGAAGTACAGAAACAGGCCTGGCCGTGGAAATGAGGAACTG
                 GATGACTCGACAGGCAAGCCGAGAGTCTACAGATGGTAGCATGAACAGCTACAGCTCA
                 GAAGGAAATCTGATTTTCCCTGGTGTTCGCTTGGCCTCTGATAGCCAGTTCAGTGATT
                 TCCTGGATGGCCTTGGCCCTGCTCAGCTAGTGGGACGCCAGACTCTGGCAACACCTGC
                 AATGGGTGACATTCAGGTAGGAATGATGGACAAAAAGGGACAGCTGGAGGTAGAAATC
                 ATCCGGGCCCGTGGCCTTGTTGTAAAACCAGGTTCCAAGACACTGCCAGCACCGTATG
                 TAAAAGTGTATCTATTAGATAACGGAGTCTGCATAGCCAAAAAGAAAACAAAAGTGGC
                 AAGAAAAACGCTGGAACCCCTTTACCAGCAGCTATTATCTTTCGAAGAGAGTCCACAA
                 GGAAAAGTTTTACAGATCATCGTCTGGGGAGATTATGGCCGCATGGATCACAAATCTT
                 TTATGGGAGTGGCCCAGATACTTTTAGATGAACTAGAGCTATCCAATATGGTGATCGG
                 ATGGTTCAAACTTTTCCCACCTTCCTCCCTAGTAGATCCAACCTTGGCTCCTCTGACA
                 AGAAGAGCTTCCCAATCATCTCTGGAAAGTTCAACTGGACCTTCTTACTCTCGTTCAT
                 AGCAGCTGTAAAAAAATTGTTGTCACAGCAACCAGCGTTACAAAAAAAAAAAAAAAAA
                 AATCACAGGTTGCAACCCTGGT
                 ORF Start: ATG at 61 ORF Stop: TAG at 4060
                 SEQ ID NO:24         1333 aa MW at 151520.5 kD
NOV12a,          MSAPVGPRGRLAPIPAASQPPLQPEMPDLSHLTEEERKIILAVMDRQKKEEEKEQSVL
CG102899-01      KKLHQQFEMYKEQVKKMGEESQQQQEQKGDAPTCGICHKTKFADGCGHNCSYCQTKFC
Protein Sequence ARCGGRVSLRSNKVMWVCNLCRKQQEILTKSGAWFYNSGSNTPQQPDQKVLRGLRNEE
                 APQEKKPKLHEQTQFQGPSGDLSVPAVEKSRSHGLTRQHSIKNGSGVKHHIASDIASD
                 RKRSPSVSRDQNRRYDQREEREEYSQYATSDTAMPRSPSDYADRRSQHEPQFYEDSDH
                 LSYRDSNRRSHRHSKEYIVDDEDVESRDEYERQRREEEYQSRYRSDPNLARYPVKPQP
                 YEEQMRIHAEVSRARHERRHSDVSLANADLEDSRISMLRMDRPSRQRSISERRAAMEN
                 QRSYSMERTREAQGPSSYAQRTTNHSPPTPRRSPLPIDRPDLRRTDSLRKQHHLDPSS
                 AVRKTKREKMETMLRNDSLSSDQSESVRPPPPKPHKSKKGGKMRQISLSSSEEELAST
                 PEYTSCDDVEIESESVSEKGDMDYNWLDHTSWHSSEASPMSLHPVTWQPSKDGDRLIG
                 RILLNKRLKDGSVPRDSGAMLGLKVVGGKMTESGRLCAFITKVKKGSLADTVGHLRPG
                 DEVLEWNGRLLQGATFEEVYNIILESKPEPQVELVVSRPIGDIPRIPDSTHAQLESSS
                 SSFESQKMDRPSISVTSPMSPGMLRDVPQFLSGQLSIKLWFDKVGHQLIVTILGAKDL
                 PSREDGRPRNPYVKIYFLPDRSDKNKRRTKTVKKTLEPKWNQTFIYSPVHRREFRERM
                 LEITLWDQARVREEESEFLGEILIELETALLDDEPHWYKLQTHDVSSLPLPHPSPYMP
                 RRQLHGESPTRRLQRSKRISDSEVSDYDCDDGIGVVSDYRHDGRDLQSSTLSVPEQVM
                 SSNHCSPSGSPHRVDVIGRTRSWSPSVPPPQSRNVEQGLRGTRTMTGHYNTISRMDRH
                 RVMDDHYSPDRDRDCEAADRQPYHRSRSTEQRPLLERTTTRSRSTERPDTNLMRSMPS
                 LMTGRSAPPSPALSRSHPRTGSVQTSPSSTPVAGRRGRQLPQLPPKGTLDRKAGGKKL
                 RSTVQRSTETGLAVEMRNWMTRQASRESTDGSMNSYSSEGNLIFPGVRLASDSQFSDF
                 LDGLGPAQLVGRQTLATPAMGDIQVGMMDKKGQLEVEIIRARGLVVKPGSKTLPAPYV
                 KVYLLDNGVCIAKKKTKVARKTLEPLYQQLLSFEESPQGKVLQIIVWGDYGRMDHKSF
                 MGVAQILLDELELSNMVIGWFKLFPPSSLVDPTLAPLTRRASQSSLESSTGPSYSRS

[0361] Further analysis of the NOV12a protein yielded the following properties shown in Table 12B.

TABLE 12B
Protein Sequence Properties NOV12a
PSort    0.9100 probability located in nucleus; 0.3000 probability
analysis located in microbody (peroxisome); 0.1000 probability
         located in mitochondrial matrix space; 0.1000 probability
         located in lysosome (lumen)
SignalP  No Known Signal Sequence Predicted
analysis:

[0362] 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.

TABLE 12C
Geneseq Results for NOV12a
		NOV12a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAB73488	Mouse Rim2, a novel isoform of	1 . . . 1097	1020/1184 (86%)	0.0
	Rim - Mus musculus, 1590 aa.	1 . . . 1182	1049/1184 (88%)
	[EP1090986-A1, 11-APR-2001]
AAW29640	Human secreted protein	1079 . . . 1333	239/296 (80%)	e−124
	C0618_1 - Homo sapiens, 374	84 . . . 374	241/296 (80%)
	aa. [WO9831802-A1, 23-JUL-1998]
AAB34848	Human secreted protein sequence	1096 . . . 1333	198/238 (83%)	e−110
	encoded by gene 46 SEQ ID	1 . . . 237	218/238 (91%)
	NO: 136 - Homo sapiens, 237 aa.
	[WO200058356-A1, 05-OCT-2000]
AAB34847	Gene 46 human secreted protein	1096 . . . 1333	197/238 (82%)	e−110
	homologous amino acid sequence	1 . . . 237	218/238 (90%)
	#135 - Rattus norvegicus, 237 aa.
	[WO200058356-A1, 05-OCT-2000]
ABB15089	Human nervous system related	983 . . . 1131	139/151 (92%)	2e−72
	polypeptide SEQ ID NO: 3746 -	1 . . . 150	140/151 (92%)
	Homo sapiens, 158 aa.
	[WO200159063-A2, 16-AUG-2001]

[0363] In a BLAST search of public sequence datbases, the NOV12a protein was found to have homology to the proteins shown in the BLASTP data in Table 12D.

TABLE 12D
Public BLASTP Results for NOV12a
		NOV12a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9JIR7	RIM2-4C - Rattus norvegicus	1 . . . 1333	1274/1333 (95%)	0.0
	(Rat), 1330 aa.	1 . . . 1330	1301/1333 (97%)
Q9JHJ6	RIM2-5C (RIM2-2A) (RIM2-	1 . . . 1333	1274/1355 (94%)	0.0
	3B) (RIM2-4A) - Rattus	1 . . . 1352	1301/1355 (95%)
	norvegicus (Rat), 1352 aa.
Q9JIR9	RIM2-3A - Rattus norvegicus	1 . . . 1333	1274/1371 (92%)	0.0
	(Rat), 1368 aa.	1 . . . 1368	1301/1371 (93%)
Q9JIS0	RIM2-2B - Rattus norvegicus	1 . . . 1333	1263/1402 (90%)	0.0
	(Rat), 1399 aa.	1 . . . 1399	1289/1402 (91%)
Q9JIR8	RIM2-4B - Rattus norvegicus	1 . . . 1333	1218/1333 (91%)	0.0
	(Rat), 1292 aa.	1 . . . 1292	1247/1333 (93%)

[0364] PFam analysis predicts that the NOV12a protein contains the domains shown in the Table 12E.

TABLE 12E
Domain Analysis of NOV12a
	NOV12a	Identities/Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
RPH3A—	5 . . . 246	65/325 (20%)	0.017
effector		120/325 (37%)
PDZ	590 . . . 677	21/90 (23%)	0.00023
		64/90 (71%)
C2	744 . . . 835	33/97 (34%)	9.6e−21
		68/97 (70%)
C2	1194 . . . 1281	33/98 (34%)	1.4e−14
		62/98 (63%)

Example 13

[0365] The NOV13 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 13A.

TABLE 13A
NOV13 Sequence Analysis
                 SEQ ID NO:25         1319 bp
NOV13a,          CATGGGCCCGGGCGGTGCCCTCCATGCCCGGGGGATGAAGACACTGCTGCCATGGACA
CG105284-01      GCCCGTGCCAGCCGCAGCCCCTAAGTCAGGCTCTCCCTCAGTTACCAGGGTCTTCGTC
DNA Sequence     AGAGCCCTTGGAGCCTGAGCCTGGCCGGGCCAGGATGGGAGTGGAGAGTTACCTGCCC
                 TGTCCCCTGCTCCCCTCCTACCACTGTCCAGGAGTGCCTAGTGAGGCCTCGGCAGGGA
                 GTGGGACCCCCAGAGCCACAGCCACCTCTACCACTGCCAGCCCTCTTCGGGACGGTTT
                 TGGCGGGCAGGATGGTGGTGAGCTGCGGCCGCTGCAGAGTGAAGGCGCTGCAGCGCTG
                 GTCACCAAGGGGTGCCAGCGATTGGCAGCCCAGGGCGCACGGCCTGAGGCCCCCAAAC
                 GGAAATGGGCCGAGGATGGTGGGGATGCCCCTTCACCCAGCAAACGGCCCTGGGCCAG
                 GCAAGAGAACCAGGAGGCAGAGCGGGAGGGTGGCATGAGCTGCAGCTGCAGCAGTGGC
                 AGTGGTGAGGCCAGTGCTGGGCTGATGGAGGAGGCGCTGCCCTCTGCGCCCGAGCGCC
                 TGGCCCTGGACTATATCGTGCCCTGCATGCGGTACTACGGCATCTGCGTCAAGGACAG
                 CTTCCTGGGGGCAGCACTGGGCGGTCGCGTGCTGGCCGAGGTGGAGGCCCTCAAACGG
                 GGTGGGCGCCTGCGAGACGGGCAGCTAGTGAGCCAGAGGGCGATCCCACCGCGCAGCA
                 TCCGTGGGGACCAGATTGCCTGGGTGGAAGGCCATGAACCAGGCTGTCGAAGCATTGG
                 TGCCCTCATGGCCCATGTGGACGCCGTCATCCGCCACTGCGCAGGGCGGCTGGGCAGC
                 TATGTCATCAACGGGCGCACCAAGGCCATGGTGGCGTGTTACCCAGGCAACGGGCTCG
                 GGTACGTAAGGCACGTTGACAATCCCCACGGCGATGGGCGCTGCATCACCTGTATCTA
                 TTACCTGAATCAGAACTGGGACGTTAAGGTGCATGGCGGCCTGCTGCAGATCTTCCCT
                 GAGGGCCGGCCCGTGGTAGCCAACATCGAGCCACTCTTTGACCGGTTGCTCATTTTCT
                 GGTCTGACCGGCGGAACCCCCACGAGGTGAAGCCAGCCTATGCCACCAGGTACGGCAT
                 CACTGTCTGGTATTTTGATGCCAAGGAGCGGGCAGCAGCCAAAGACAAGTATCAGCTA
                 GCATCAGGACAGAAAGGTGTCCAAGTACCTGTATCACAGCCGCCTACGCCCACCTAGT
                 GGCCAGTCCCAGAGCCGCATGGCAGACAGCTTAAATGACTTCA
                 ORF Start: ATG at 52 ORF Stop: TAG at 1273
                 SEQ ID NO:26         407 aa MW at 43635.9 kD
NOV13a,          MDSPCQPQPLSQALPQLPGSSSEPLEPEPGRARMGVESYLPCPLLPSYHCPGVPSEAS
CG105284-01      AGSGTPRATATSTTASPLRDGFGGQDGGELRPLQSEGAAALVTKGCQRLAAQGARPEA
Protein Sequence PKRKWAEDGGDAPSPSKRPWARQENQEAEREGGMSCSCSSGSGEASAGLMEEALPSAP
                 ERLALDYIVPCMRYYGICVKDSFLGAALGGRVLAEVEALKRGGRLRDGQLVSQRAIPP
                 RSIRGDQIAWVEGHEPGCRSIGALMAHVDAVIRHCAGRLGSYVINGRTKAMVACYPGN
                 GLGYVRHVDNPHGDGRCITCIYYLNQNWDVKVHGGLLQIFPEGRPVVANIEPLFDRLL
                 IFWSDRRNPHEVKPAYATRYGITVWYFDAKERAAAKDKYQLASGQKGVQVPVSQPPTP
                 T

[0366] Further analysis of the NOV13a protein yielded the following properties shown in Table 13B.

TABLE 13B
Protein Sequence Properties NOV13a
PSort    0.3000 probability located in nucleus; 0.1818 probability
analysis located in lysosome (lumen); 0.1000 probability
         located in mitochondrial matrix space; 0.0000 probability
         located in endoplasmic reticulum (membrane)
SignalP  No Known Signal Sequence Predicted
analysis:

[0367] 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 13C.

TABLE 13C
Geneseq Results for NOV13a
		NOV13a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
ABG08029	Novel human diagnostic protein	114 . . . 388	161/280 (57%)	6e−88
	#8020 - Homo sapiens, 284 aa.	3 . . . 276	192/280 (68%)
	[WO200175067-A2, 11-OCT-2001]
ABG08029	Novel human diagnostic protein	114 . . . 388	161/280 (57%)	6e−88
	#8020 - Homo sapiens, 284 aa.	3 . . . 276	192/280 (68%)
	[WO200175067-A2, 11-OCT-2001]
AAB10873	Human tumor-associated antigen	175 . . . 388	132/215 (61%)	1e−80
	9D7 protein - Homo sapiens, 239	12 . . . 226	167/215 (77%)
	aa. [DE19909503-A1, 07-SEP-2000]
ABB03740	Human musculoskeletal system	281 . . . 407	125/127 (98%)	6e−73
	related polypeptide SEQ ID NO:	24 . . . 150	126/127 (98%)
	1687 - Homo sapiens, 150 aa.
	[WO200155367-A1, 02-AUG-2001]
AAB63118	Human secreted protein sequence	281 . . . 388	106/108 (98%)	2e−61
	encoded by gene 40 SEQ ID	1 . . . 108	107/108 (98%)
	NO: 128 - Homo sapiens, 108 aa.
	[WO200061748-A1, 19-OCT-2000]

[0368] In a BLAST search of public sequence datbases, the NOV13a protein was found to have homology to the proteins shown in the BLASTP data in Table 13D.

TABLE 13D
Public BLASTP Results for NOV13a
		NOV13a	Identities/
Protein		Residues/	Similarities
Accession		Match	for the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q96KS0	EGLN2 PROTEIN - Homo	1 . . . 407	406/407 (99%)	0.0
	sapiens (Human), 407 aa.	1 . . . 407	406/407 (99%)
Q8WWY4	ESTROGEN-INDUCED TAG 6 -	1 . . . 407	405/407 (99%)	0.0
	Homo sapiens (Human), 407 aa.	1 . . . 407	405/407 (99%)
Q8VHJ1	EGLN2 - Mus musculus (Mouse),	1 . . . 407	369/421 (87%)	0.0
	419 aa.	1 . . . 419	381/421 (89%)
Q99MI0	CELL GROWTH REGULATOR	1 . . . 407	368/421 (87%)	0.0
	FALKOR - Mus musculus	1 . . . 419	381/421 (90%)
	(Mouse), 419 aa.
Q91YE2	EGLN2 PROTEIN - Mus	1 . . . 407	362/421 (85%)	0.0
	musculus (Mouse), 419 aa.	1 . . . 419	373/421 (87%)

[0369] PFam analysis predicts that the NOV13a protein contains the domains shown in the Table 13E.

TABLE 13E
Domain Analysis of NOV13a
Pfam	NOV13a	Identities/	Expect Value
Domain	Match Region	Similarities
		for the Matched Region

Example 14

[0370] The NOV14 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 14A.

TABLE 14A
NOV14 Sequence Analysis
                 SEQ ID NO:27         2602 bp
NOV14a,          TTCGGGTTCCAGACCCAAGGCTGCGTGTTCTCCACCGCTTGTTGTGGCCAGTGTTACT
CG105444-01      GCGGTGACCGCCAGAGCAGCCTCGACGCTATGGAGGAGCCTGGTGCTACCCCTCAGCC
DNA Sequence     CTACCTGGGGCTGGTCCTGGAGGAGCTAGGCAGAGTTGTGGCAGCACTACCTGAGAGT
                 ATGAGACCAGATGAGAATCCTTATGGTTTTCCATCGGAACTGGTGGTATGTGCAGCTG
                 TTATTGGATTTTTTGTTGTTCTCCTTTTTTTGTGGAGAAGTTTTAGATCGGTTAGGAG
                 TCGGCTTTATGTGGGAAGAGAGCAAAAACTTGGTGCAACGCTTTCTGGACTAATTGAA
                 GAAAAATGTAAACTACTTGAAAAGTTTAGCCTTATTCAAAAAGAGTATGAAGGCTATG
                 AAGTAGAGTCATCTTTAGAGGATGCCAGCTTTGAGAAGGCGGCAGCAGAAGAAGCACG
                 AAGTTTGGAGGCAACCTGTGAAAAGCTGAGCAGGTCCAATTCTGAACTTGAGGATGAA
                 ATCCTCTGTCTAGAAAAAGACTTAAAAGAAGAGAAATCTAAACATTCTCAACAAGATG
                 AATTGATGGCGGATATTTCAAAAAGTATACAGTCTCTAGAAGATGAGTCAAAATCCCT
                 CAAATCACAAATAGCTGAAGCCAAAATCATCTGCAAGACATTTAAAATGAGTGAAGAA
                 CGACGGGCTATAGCAATAAAAGATGCTTTGAATGAAAATTCTCAACTTCAGACAAGCC
                 ATAAACAGCTTTTTCAGCAAGAAGCTGAAGTATGGAAAGGACAAGTGAGTGAACTTAA
                 TAAACAGAAAATAACATTTGAAGACTCCAAAGTACACGCAGAACAAGTTCTGAATGAT
                 AAAGAAAATCACATCAAGACCCTGACTGGACACTTGCCAATGATGAAAGATCAGGCTG
                 CTGTGCTTGAAGAAGACACAACGGATGATGATAACCTGGAATTAAAAGTGAACAGTCA
                 ATGGGAAAATGGTGCTAACTTAGATGATCCTCCGAAAGGAGCTTTGAAGAAACTGATT
                 CATGCTGCTAAGTTAAATGTTTCTTTAAAAAGCTTAGAAGGAGAAAGAAACCACATTA
                 TTATTCAGTTATCTGAAGTGGACAAAACAAAGGAAGAGCTTACAGAGCATATTAAAAA
                 TCTTCAGACTCAACAAGCATCTTTGCAATCAGAAAACATATATTTTGAAAGTGAGAAT
                 CAGAAGCTTCAACAGAAACTTAAAATAATGACTGAATTCTATCAAGAAAATGAAATGA
                 AACTCTACAGGAAATTAACAGTGGAGGAAAATTACCGAATAGAGGAAGAAGAGAAGCT
                 TTCTAGAGTGGAAGAAAAGATCAGCCATGCCACTGAAGAGCTGGAGACCTATAGAAAG
                 CTAGCCAAAGATCTTGAAGAAGAATTGGAGAGAACTGTTCATTTTTATCAAAAGCAGG
                 TTATTTCCTACGAGAAAAGAGGACATGATAATTGGTTGGCAGCTCGGACTGCTGAAAG
                 AAACCTCAGTGATTTAAGGAAAGAAAATGCTCACAACAAACAAAAATTAACTGAAAGA
                 GAGTTGAAATTTGAACTTTTAGAAAAAGATCCTAATGCACTCGATGTTTCAAATACAG
                 CATTTGGCAGAGAGCATTCCCCATGTAGTCCCTCACCATTGGGTCGGCCTTCATCTGA
                 AACGAGAGCTTTTCCCTCTCCTCAAACTTTGTTGGAGGATCCACTCAGACTCTCACCT
                 GTGCTTCCAGGGGGAGGAGGAAGAGGCCCAAGCAGCCCAGGGAATCCCCTGGACCATC
                 AGATTACCAATGAAAGAGGAGAACCAAGCTATGACAGGTTAATCGATCCTCACAGGGC
                 TCCTTCTGACACTGGGTCCCTGTCATCTCCGGTGGAACAGGACCGTAGGATGATGTTT
                 CCTCCACCAGGGCAATCATATCCTGATTCAACTCTTCCTCCACAAAGGGAAGACAGAT
                 TTTATTCTAATTCTGAAAGACTGTCTGGACCAGCAGAACCCAGAAGTTTTAAAATGAC
                 TTCTTTGGATAAAATGGATAGGTCAATGCCTTCAGAAATGGAATCCAGTAGAAATGAT
                 GCCAAAGATGATCTTGGTAATTTAAATGTGCCTGATTCATCTCTCCCTGCTGAAAATG
                 AAGCAACTGGCCCTGGCCTTATTCCTCCACCTCTTGCTCCAATCAGCGGTCCATTGTT
                 TCCAGTGGATACAAGGGGCCCATTCATGAGAAGAGGACCTCCTTTCCCCCCACCTCCT
                 CCAGGAACCATGTTTGGAGCTTCTCGAGGTTATTTTCCACCAAGGGATTTCCCAGGTC
                 CACCACATGCTCCATTTGCAATGAGAAACATCTATCCACCGAGGGGTTTACCTCCTTA
                 CCTTCATCCGAGACCTGGATTTTACCCCAACCCCCCACATTCTGAAGGTAGAAGCGAG
                 TTCCCTTCAGGATTGATTCCGCCTTCAAAGGAGCCTGCTACTGGACATCCAGAACCAC
                 AGCAAGACACCTGACAATATTGTTGCTTTCTTCAAAAGTAATTTTGACTGATCTCATT
                 TTCAGTTTAAGTAACTGCTGTTACTTAAGTGATTGCACTTTTCTCAAATT
                 ORF Start: ATG at 88 ORF Stop: TGA at 2506
                 SEQ ID NO:28         806 aa MW at 90996.1 kD
NOV14a,          MEEPGATPQPYLGLVLEELGRVVAALPESMRPDENPYGFPSELVVCAAVIGFFVVLLF
CG105444-01      LWRSFRSVRSRLYVGREQKLGATLSGLIEEKCKLLEKFSLIQKEYEGYEVESSLEDAS
Protein Sequence FEKAAAEEARSLEATCEKLSRSNSELEDEILCLEKDLKEEKSKHSQQDELMADISKSI
                 QSLEDESKSLKSQIAEAKIICKTFKMSEERRAIAIKDALNENSQLQTSHKQLFQQEAE
                 VWKGQVSELNKQKITFEDSKVHAEQVLNDKENHIKTLTGHLPMMKDQAAVLEEDTTDD
                 DNLELKVNSQWENGANLDDPPKGALKKLIHAAKLNVSLKSLEGERNHIIIQLSEVDKT
                 KEELTEHIKNLQTQQASLQSENIYFESENQKLQQKLKIMTEFYQENEMKLYRKLTVEE
                 NYRIEEEEKLSRVEEKISHATEELETYRKLAKDLEEELERTVHFYQKQVISYEKRGHD
                 NWLAARTAERNLSDLRKENAHNKQKLTERELKFELLEKDPNALDVSNTAFGREHSPCS
                 PSPLGRPSSETRAFPSPQTLLEDPLRLSPVLPGGGGRGPSSPGNPLDHQITNERGEPS
                 YDRLIDPHRAPSDTGSLSSPVEQDRRMMFPPPGQSYPDSTLPPQREDRFYSNSERLSG
                 PAEPRSFKMTSLDKMDRSMPSEMESSRNDAKDDLGNLNVPDSSLPAENEATGPGLIPP
                 PLAPISGPLFPVDTRGPFMRRGPPFPPPPPGTMFGASRGYFPPRDFPGPPHAPFAMRN
                 IYPPRGLPPYLHPRPGFYPNPPHSEGRSEFPSGLIPPSKEPATGHPEPQQDT

[0371] Further analysis of the NOV14a protein yielded the following properties shown in Table 14B.

TABLE 14B
Protein Sequence Properties NOV14a
PSort     0.6000 probability located in endoplasmic reticulum
analysis: (membrane); 0.3000 probability located
          in microbody (peroxisome);
          0.1000 probability located in mitochondrial inner membrane;
          0.1000 probability located in plasma membrane
SignalP   Cleavage site between residues 69 and 70
analysis:

[0372] 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 14C.

TABLE 14C
Geneseq Results for NOV14a
		NOV14a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAM05968	Peptide #4650 encoded by probe	1 . . . 775	775/775 (100%)	0.0
	for measuring breast gene	1 . . . 775	775/775 (100%)
	expression - Homo sapiens, 777 aa.
	[WO200157270-A2, 09-AUG-2001]
AAM30846	Peptide #4883 encoded by probe	1 . . . 775	775/775 (100%)	0.0
	for measuring placental gene	1 . . . 775	775/775 (100%)
	expression - Homo sapiens, 777 aa.
	[WO200157272-A2, 09-AUG-2001]
AAM18368	Peptide #4802 encoded by probe	1 . . . 775	775/775 (100%)	0.0
	for measuring cervical gene	1 . . . 775	775/775 (100%)
	expression - Homo sapiens, 777 aa.
	[WO200157278-A2, 09-AUG-2001]
AAM58083	Human brain expressed single	1 . . . 775	775/775 (100%)	0.0
	exon probe encoded protein SEQ	1 . . . 775	775/775 (100%)
	ID NO: 30188 - Homo sapiens,
	777 aa. [WO200157275-A2, 09-AUG-2001]
ABB22697	Protein #4696 encoded by probe	1 . . . 775	775/775 (100%)	0.0
	for measuring heart cell gene	1 . . . 775	775/775 (100%)
	expression - Homo sapiens, 777 aa.
	[WO200157274-A2, 09-AUG-2001]

[0373] In a BLAST search of public sequence datbases, the NOV14a protein was found to have homology to the proteins shown in the BLASTP data in Table 14D.

TABLE 14D
Public BLASTP Results for NOV14a
		NOV14a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
O95046	WUGSC: H_DJ0988G15.3	1 . . . 775	775/775 (100%)	0.0
	PROTEIN (DJ1005H11.2)	1 . . . 775	775/775 (100%)
	(WUGSC: H_DJ0988G15.3
	PROTEIN) - Homo sapiens
	(Human), 777 aa.
O15320	Meningioma-expressed antigen	1 . . . 806	675/806 (83%)	0.0
	6/11 (MEA6) (MEA11) - Homo	1 . . . 804	721/806 (88%)
	sapiens (Human), 804 aa.
Q96SG9	BA500G10.2 (NOVEL PROTEIN	1 . . . 806	650/806 (80%)	0.0
	SIMILAR TO MENINGIOMA	15 . . . 816	700/806 (86%)
	EXPRESSED ANTIGEN 6
	(MEA6) AND 11 (MEA11)) -
	Homo sapiens (Human), 825 aa
	(fragment).
Q96RT6	CTAGE-2 - Homo sapiens	30 . . . 787	590/758 (77%)	0.0
	(Human), 754 aa.	1 . . . 754	641/758 (83%)
AAH26864	SIMILAR TO MENINGIOMA	30 . . . 804	536/785 (68%)	0.0
	EXPRESSED ANTIGEN 6	1 . . . 778	612/785 (77%)
	(COILED-COIL PROLINE-RICH) -
	Mus musculus (Mouse), 779 aa.

[0374] PFam analysis predicts that the NOV14a protein contains the domains shown in the Table 14E.

TABLE 14E
Domain Analysis of NOV14a
Pfam	NOV14a	Identities/	Expect Value
Domain	Match Region	Similarities
		for the Matched Region

Example 15

[0375] The NOV15 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 15A.

TABLE 15A
NOV15 Sequence Analysis
                 SEQ ID NO:29         2614 bp
NOV15a,          GGATTCGGGTTCCAGACCCAAGGCTGCGTGTTCTCCACCGTTTGTTGTGGCCAGTGTT
CG105482-01      ACTGTGGTGACCGCCAGAGCAGCCTTCGCGCTATGGAGGAGCCCGGTGCTACCCCTCA
DNA Sequence     GCCCTACCTGGGGCTGGTCCTGGAGGAGCTACGCAGAGTTGTGGCAGCACTACCTGAG
                 AGTATGACGGCAGATTCGAATCCTTATGGTTTTCCATGGGAACTGGTGGTATGTGCAG
                 CTGTTGTTGGATTTTTTGTTGTTCTCCTTTTTTTGTGGAGAAGTTTTAGATCGGTTAG
                 GAGTCGGCTTTATGTGGGAAGAGAGAAAAAACTTGGTGAAACGCTTTCTGGACTAATT
                 GAAGAAAAATGTAAACTACTTGAAAAATTTAGCCTTATTCAAAAAGAGTATGAAGGCT
                 ATGAAGTAGAGTCATCTTTAGAGGATGCCAGCTTTGAGAAGGCGGTAGCAGAAGCACG
                 AAGTTTGGAGGCAACCTGTGAAAAGCTGAACAGGTCCAATTCTGAACTTGAGGATGAA
                 ACCCTCTGTCTAGAAAAAGAGTTAAGGGAAATCAAATCTAAACATTCTCAACAAGATG
                 AATTGATGGCGGATATTTCTAAAAGGATACAATCTCTAGAAGATGAGTCAAAATCCCT
                 CAAATCACAAATAGCTGAAGCCAAAATCATCTGCAAGATTTTTCAAGCGACTGAAGAA
                 CGATGGGCAATAGCAATAAAAGATGCTTTGAATAAAAATTCTCAACTTCACGAAAGCC
                 AGAAACAGCTTTTGCAAGAAGCTGAAGTATGGAAAGAACAAGTGAGTGAACTTAATAA
                 ACAGAAAATAACATTTGAAGACTCCAAAGTACATGCAGAACAAGTTCTAAATGATAAA
                 ATCAATCACATCAAGACCCTGACTGGACACTTGCCAATGATGAACGATCAGGCTGCTG
                 TGCTTGAAGAAGACACAACGGATGATGATAACTTGGAATTAGAAGTGAACAGTCAATC
                 GGAAAATGGTGCTTATTTAGATGATCCTCCAAAAGGAGCTTTGAAGAAACTGATTCAT
                 GCTGCTAAGTTAAATGTTTCTTTAAAAACCTTAGAAGGAGAAAGAAACCACATTATTA
                 TTCAGTTATCTGAAGTGGACAAAACAAAGGAAGAGCTTACAGAGCATATTAAAAATCT
                 TCAGACTCAACAAGCATCTTTGCAGTCAGAAAACATATATTTTGAAAGTGAGAATCAG
                 AAGCTTCAACAGAAACTTAAAATAATGACTGAATTATATCAAGAAAATGAAATGACAC
                 TCCACAGGAAATTGACAATAGAGGAAAATTACTGGATAGAGGAAGAAGAGAAGCTTTC
                 TAAAGTGGAAGAAAAGATCAGCCATGCCACTGAAGAGCTGGAGACCTATAGAAAGCTA
                 GCCAAAGATCTTGAAGAAGAATTGGAGAGAACTGTTCATTTTTATCAAAAGCAGGTTA
                 TTTCCTACGAGAAAAAAGGACATGATAATTGGTTGGCAGCTCGGACTGCTGAAAGAAA
                 CCTCAATGATTTAAGGAAAGAAAATGCTCACAACAAACAAAAATTAACTGAAACAGAG
                 TTTAAATTTGAAGTTTTAGAAAAAGATCCTAATGCACTTGATGTTTCAAATACAGCAT
                 CTGGCAGAGAGCATTCCCCATATGGTCCCTCACCATTGGGTCGGCCTTCATCTGAAAC
                 GAGGACTTCTCTCTCCCCTCAAACTTTGTTGGAGGATCCACTCAGACTCTCACCTGTG
                 CTTCCAGCGGGAGGAGGAAGAAGCCCAAGCGGCCGAGAGAATCCTCTGGACCATCAGA
                 TTACCAATGAAAGAGGAGAACCAAGCTGTGATAGGTTAACTGATCCTCACAGAGCTCC
                 TTCTGACACTGGGTCCCTGTCATCTCCATGGGAACAGGACCATAGGATGATGTTTCCT
                 CCACCAGGACAATCATATCCTGATTCAGCTCTTCCTCCACAAAGGGAAGACAGATTTT
                 ATTCTAATTCTGATAGACTGCCTGGACCATCAGAACTCAGAAGTTTTAATATGCCTTC
                 TTTGGATAAAATGGATGGGTCAATGCCTTCAGAAATGGAATCCACTAGACATGATGCC
                 AAAGATGATCCTGGTAGTTTAAATGTGCCTGATTCATCTCTCCCTGCTGAAAATGAAG
                 CAACTGGCCCCGGCTTTATTCCTCCACCTCTTGCTCCAATCAGTGGTCCATTGTTTCC
                 AGTGGACACAAGGTGCCCGTTCATGAGAAGAGGACCTCTTTTCCCCCAACCTCCTCCA
                 GGAACGATGTTTGGAGCTTCACAAGGTTATTTTCCACCAAGGGATTTCCCAGGTCCAC
                 CACATGTTCCATTTGCAATGAGAAACATCTGTCCACTGAGGGGTTTACCTCCTTACTT
                 TCATCCAAGACCTGGATTTTACCCCAACCCCCCACATTCTGAAGGTAGAAGCGAGTTC
                 CCTTCATGGTTGATTCTGCCTTTAAAGGAGCCTGCTACTGAACATCCAGAACCACAGC
                 AAGAAACCTGACAATATTTTTGCTTTCTTCAAAAGTAATTTTGACTGATCTCATTTTC
                 AGTTTAAGTAACTGCTGTTACTTAAGTGATTACACTTTTCTCAAATTGAAGTTTAATG
                 GAAT
                 ORF Start: ATG at 91 ORF Stop: TGA at 2503
                 SEQ ID NO:30         804 aa MW at 91231.4 kD
NOV15a,          MEEPGATPQPYLGLVLEELRRVVAALPESMTADSNPYGFPWELVVCAAVVGFFVVLLF
CG105482-01      LWRSFRSVRSRLYVGREKKLGETLSGLIEEKCKLLEKFSLIQKEYEGYEVESSLEDAS
Protein Sequence FEKAVAEARSLEATCEKLNRSNSELEDETLCLEKELREIKSKHSQQDELMADISKRIQ
                 SLEDESKSLKSQIAEAKIICKIFQATEERWAIAIKDALNKNSQLHESQKQLLQEAEVW
                 KEQVSELNKQKITFEDSKVHAEQVLNDKINHIKTLTGHLPMMNDQAAVLEEDTTDDDN
                 LELEVNSQSENGAYLDDPPKGALKKLIHAAKLNVSLKTLEGERNHIIIQLSEVDKTKE
                 ELTEHIKNLQTQQASLQSENIYFESENQKLQQKLKIMTELYQENEMTLHRKLTIEENY
                 WIEEEEKLSKVEEKISHATEELETYRKLAKDLEEELERTVHFYQKQVISYEKKGHDNW
                 LAARTAERNLNDLRKENAHNKQKLTETEFKFEVLEKDPNALDVSNTASGREHSPYGPS
                 PLGRPSSETRTSLSPQTLLEDPLRLSPVLPAGGGRSPSGRENPLDHQITNERGEPSCD
                 RLTDPHRAPSDTGSLSSPWEQDHRMMFPPPGQSYPDSALPPQREDRFYSNSDRLPGPS
                 ELRSFNMPSLDKMDGSMPSEMESTRHDAKDDPGSLNVPDSSLPAENEATGPGFIPPPL
                 APISGPLFPVDTRCPFMRRGPLFPQPPPGTMFGASQGYFPPRDFPGPPHVPFAMRNIC
                 PLRGLPPYFHPRPGFYPNPPHSEGRSEFPSWLILPLKEPATEHPEPQQET

[0376] Further analysis of the NOV15a protein yielded the following properties shown in Table 15B.

TABLE 15B
Protein Sequence Properties NOV15a
PSort     0.6000 probability located in endoplasmic
analysis: reticulum (membrane);
          0.3000 probability located in microbody (peroxisome);
          0.1000 probability located in mitochondrial inner membrane;
          0.1000 probability located in plasma membrane
SignalP   Cleavage site between residues 69 and 70
analysis:

[0377] 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 15C.

TABLE 15C
Geneseq Results for NOV15a
		NOV15a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAY77574	Human cytoskeletal protein	1 . . . 804	696/806 (86%)	0.0
	(HCYT) (clone 3768043) - Homo	1 . . . 806	731/806 (90%)
	sapiens, 806 aa. [WO200006730-
	A2, 10-FEB-2000]
AAM05968	Peptide #4650 encoded by probe for	1 . . . 773	694/775 (89%)	0.0
	measuring breast gene expression -	1 . . . 775	716/775 (91%)
	Homo sapiens, 777 aa.
	[WO200157270-A2, 09-AUG-2001]
AAM30846	Peptide #4883 encoded by probe for	1 . . . 773	694/775 (89%)	0.0
	measuring placental gene	1 . . . 775	716/775 (91%)
	expression - Homo sapiens, 777 aa.
	[WO200157272-A2, 09-AUG-2001]
AAM18368	Peptide #4802 encoded by probe for	1 . . . 773	694/775 (89%)	0.0
	measuring cervical gene expression -	1 . . . 775	716/775 (91%)
	Homo sapiens, 777 aa.
	[WO200157278-A2, 09-AUG-2001]
AAM58083	Human brain expressed single exon	1 . . . 773	694/775 (89%)	0.0
	probe encoded protein SEQ ID NO:	1 . . . 775	716/775 (91%)
	30188 - Homo sapiens, 777 aa.
	[WO200157275-A2, 09-AUG-2001]

[0378] In a BLAST search of public sequence datbases, the NOV15a protein was found to have homology to the proteins shown in the BLASTP data in Table 15D.

TABLE 15D
Public BLASTP Results for NOV15a
		NOV15a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
O95046	WUGSC: H_DJ0988G15.3	1 . . . 773	694/775 (89%)	0.0
	PROTEIN (DJ1005H11.2)	1 . . . 775	716/775 (91%)
	(WUGSC: H_DJ0988G15.3
	PROTEIN) - Homo sapiens
	(Human), 777 aa.
O15320	Meningioma-expressed antigen 6/11	1 . . . 804	672/804 (83%)	0.0
	(MEA6) (MEA11) - Homo sapiens	1 . . . 804	715/804 (88%)
	(Human), 804 aa.
Q96SG9	BA500G10.2 (NOVEL PROTEIN	1 . . . 804	641/804 (79%)	0.0
	SIMILAR TO MENINGIOMA	15 . . . 816	695/804 (85%)
	EXPRESSED ANTIGEN 6 (MEA6)
	AND 11 (MEA11)) - Homo sapiens
	(Human), 825 aa (fragment).
Q96RT6	CTAGE-2 - Homo sapiens	30 . . . 782	592/753 (78%)	0.0
	(Human), 754 aa.	1 . . . 751	643/753 (84%)
AAH26864	SIMILAR TO MENINGIOMA	30 . . . 802	532/783 (67%)	0.0
	EXPRESSED ANTIGEN 6	1 . . . 778	609/783 (76%)
	(COILED-COIL PROLINE-RICH) -
	Mus musculus (Mouse), 779 aa.

[0379] PFam analysis predicts that the NOV15a protein contains the domains shown in the Table 15E.

TABLE 15E
Domain Analysis of NOV15a
Pfam	NOV15a	Identities/	Expect Value
Domain	Match Region	Similarities
		for the Matched Region

Example 16

[0380] The NOV16 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 16A.

TABLE 16A
NOV16 Sequence Analysis
                 SEQ ID NO:31         3813 bp
NOV16a,          GCCCTGCCAACCCCCACCATGTGTGAGGTGATGCCCACAATCAATGAGGGGGACCTCT
CG105617-01      GGGGTCCCCTCCATGGCGCCGATGCTGACGCCAACTTCGAGCAGCTGATGGTGAACAT
DNA Sequence     GCTGGACGAGCGGGAGAAGTTGCTGGAGTCTCTTCGGGAGAGTCAGGAGACCTTGGCG
                 GCCACACAGAGCCGGCTCCAGGATGCCATACACGAGCGGGACCAGCTCCAGCGCCACC
                 TTAACTCCGCCCTCCCCCAGAATCCTGAAGCACTGAGGGGCCTTGGGGGTTTTCAGGA
                 ATTTGCCACCTTAACCCGGGAGCTGAGCATGTGTCGGGAGCAGCTTCTAGAGCGGGAG
                 GAAGAGATATCAGAACTGAAAGCAGAACGGAATAACACACGGCTGCTTCTGGAACATC
                 TGGAGTGCCTGGTGTCCCGCCATGAACGGTCACTGCGGATGACTGTGGTGAAGCGCCA
                 GGCCCAGTCACCTTCGGGGGTCTCCAGTGAGGTGGAGGTGCTGAAGGCCCTCAAGTCA
                 CTGTTTGAGCACCACAAGGCCCTGGATGAGCAGGTGCGAGAGCGGCTCCGGGCAGCGC
                 TGGAGCGAGTCACCACCTTGGAGGAGCAGCTGGCAGGTGCCCACCAGCAGGTAATCTG
                 CCTGCTCACCCTCAGTCTGCAGCTCCTGGAAGTCCAGGCTGGTTCACCCCTGTGCCCT
                 ACTCTGTTTCTTGTCAGATTTCTCCCTGCCATGGCTGGAAGCTGCCTGCTCACAGAGC
                 TACTGTCCCTATCCCTGGAGGAGGATACGGGCCGGGTAGAGGAGCTGCAGGAGCTCCT
                 GGAGAAGCAGAACTTTGAGTTGAGCCAGGCCCGGGAGCGACTGGTCACCCTAACAACA
                 ACCGTGACTGAACTCGAGGAGGACCTGGGCACGGCCCGCCGGGACCTCATCAAGTCGG
                 AGGAGCTGAGCAGCAAGCATCAGCGGGACCTCCGGGAGGCTCTGGCCCAGAAGGAGGA
                 CATGGAAGAGCGGATTACTACACTGGAGAAGCGCTACCTGGCTGCTCAGCGTGAGGCA
                 ACATCCATCCATGACCTCAATGACAAGCTGGAGAATGAGCTGGCCAACAAGGAGTCCC
                 TGCACCGCCAGGTAGAGGAGAAGGCCCGACACCTGCAGGAGCTGCTGGAGGTGGCAGA
                 GCAGAAGCTGCAGCAGACGATGCGCAAGGCAGAGACGCTGCCAGAGGTGGAGGCTGAG
                 CTGGCCCAGAGAATTGCAGCCCTCACCAAGGCAGAAGAACGGCATGGCAACATTGAGG
                 AGCACCTGCGGCAGCTGGAGGGACAGCTGGAGGAGAAGAACCAGGAGCTGGCACGGGT
                 GAGGCAGCGGGAAAAGATGAATGAGGACCACAACAAGCGGCTGTCGGACACAGTGGAC
                 CGGCTGCTCAGCGAGTCCAACGAGCGTCTGCAGCTCCACCTGAAGGAGCGCATGGCTG
                 CCCTGGAGGAGAAGGTGCCCAGAGGGGCGGGGTTGGGATGCGAGAGGTTAGTGCTGGG
                 TGTGGGGCGGGGGGAGGCGGGACTGCTGTCTGAAGAGATTGAGAAGCTGCGCCAAGAG
                 GTGGACCAGCTGAAGGGCCGAGGGGGGCCGTTTGTGGATCATCACCGCTCAAGGTCGC
                 ACATGGGCAGTGCAGCAGACGTGCGGTTCTCCCTGGGCACAACCACACACGCACCCCC
                 AGGCGTGCATCGCCGCTACTCGGCATTGAGGGAAGAGTCTGCCAAGGTGAGGGGGTGG
                 AGGGATCTCCTCAGGGAGTTTGGGGTCAATTCGGCCGACTGGGAGACTTCTCCACTGC
                 CTGGGATGCTGGCCCCGGCAGCTGGCCCTGCCTTTGACAGTGACCCTGAGATCTCCGA
                 CGTGGATGAGGATGAGCCAGGGGGTCTGGTGGGCTCTGCGGATGTTGTCTCCCCCAGC
                 GGCCACTCAGATGCCCAGACCCTGGCCATGATGCTGCAGGAGCAGCTGGATGCCATCA
                 ATGAGGAAATCAGGTTAATTCAGGAAGAGAAGGAGTCCACGGAGCTCCGCGCGGAGGA
                 GATTGAGACGCGTGTAACCAGTGGCAGCATGGAAGCCCTAAACCTGAAGCAGCTGCGC
                 AAGCGTGGTTCCATCCCCACCTCTCTGACGGCCCTGTCCCTGGCCAGCGCGTCCCCAC
                 CACTCAGCGGCCGCTCCACACCTAAGCTCACCTCCCGCAGTGCTGCCCAGGACCTGGA
                 CCGAATGGGGGTCATGACCCTGCCCAGTGACTTAAGAAAGCATAGGAGGAAGCTGCTG
                 TCGCCAGTGTCTCGGGAAGAGAACCGAGAGGATAAAGCCACCATAAAATGTGAGACTT
                 CTCCTCCTTCCTCACCCAGGACGCTGCGGCTAGAGAAGCTTGGCCACCCAGCCCTGAG
                 CCAGGAAGAAGGCAAGAGTGCCTTGGAGGATCAGGGCAGCAACCCCAGCAGCAGCAAC
                 AGCAGCCAGGACTCCCTGCACAAGGGCGCCAAGCGCAAGGGCATCAAGTCGTCCATTG
                 GCCGCCTGTTTGGGAAGAAGGAGAAGGGCAGGCTGATCCAGCTGAGTCGGGATGGAGC
                 CACAGGCCATGTTCTGCTAACAGACTCCGAATTCAGTATGCAGGAGCCTATGGTGCCT
                 GCCAAGCTGGGGACCCAGGCAGAGAAGGACCGGCGGCTAAAGAAGAAACACCAGCTGC
                 TTGAAGATGCCCGCAGGAAAGGAATGCCCTTTGCCCAGTGGGATGGTCCTACTGTGGT
                 CTCCTGGTTGGAGCTCTGGGTGGGGATGCCTGCCTGGTATGTGGCAGCCTGCCGGGCC
                 AACGTCAAGAGTGGTGCCATCATGTCCGCTCTGTCGGACACAGAGATCCAGCGGGAGA
                 TCGGCATCAGCAATGCCCTGCACCGGCTCAAGCTCCGCCTGGCCATTCAGGAGATGGT
                 GTCATTGACCAGCCCCTCTGCCCCACCCACCTCCAGGACTTCTTCTGGGAATGTCTGG
                 GTCACCCATGAAGAGATGGAAACTCTGGAAACATCTACTAAAACAGACAGTGAGGAGG
                 GCAGCTGGGCTCAGACCCTGGCCTATGGGGACATGAACCATGAGTGGATTGGGAATGA
                 ATGGCTACCCAGCCTGGGGCTCCCGCAGTACCGCAGCTACTTCATGGAGTGCCTGGTG
                 GACGCCCGCATGCTGGACCACCTCACCAAGAAGGACCTGCGGGTCCACCTGAAGATGG
                 TGGACAGCTTCCATCGAACCAGTCTTCAGTATGGCATCATGTGTCTGAAGAGGCTGAA
                 TTATGACCGGAAGGAGCTGGAGAAGAGGCGAGAGGAGAGCCAGCATGAGATCAAGGAT
                 GTGTTAGTCTGGACCAACGACCAGGTGGTTCATTGGGTCCAGTCTATTGGGCTCCGGG
                 ACTACGCAGGAAACCTGCATGAGAGTGGTGTGCATGGAGCCTTGCTGGCCCTGGACGA
                 GAACTTCGACCACAACACACTGGCCCTGATCCTCCAGATCCCCACACAGAACACCCAG
                 GCACGCCAAGTGATGGAAAGAGAGTTCAATAACCTGTTGGCCTTGGGCACAGACCGGA
                 AGCTGGATGACGGGGATGACAAGGTGTTTCGCCGCGCGCCCTCCTGGAGGAAGCGCTT
                 CCGGCCGCGGGAGCACCACGGTCGCGGCGGCATGCTCAGCGCTTCCGCGGAGACCCTC
                 CCGGCGGGCTTCCGTGTGTCCACCCTGGGGACCCTGCAGCCCCCACCGGCCCCGCCAA
                 AGAAGATCATGCCTGAAGCTCACTCCCACTATCTCTACGGACACATGCTCTCCGCCTT
                 CCGGGACTAGCCATGGCCCCCAGGGCTGGCTTCCTCCTTCTGG
                 ORF Start: ATG at 19 ORF Stop: TAG at 3778
                 SEQ ID NO:32         1253 aa MW at 141282.1 kD
NOV16a,          MCEVMPTINEGDLWGPLHGADADANFEQLMVNMLDEREKLLESLRESQETLAATQSRL
CG105617-01      QDAIHERDQLQRHLNSALPQNPEALRGLGGFQEFATLTRELSMCREQLLEREEEISEL
Protein Sequence KAERNNTRLLLEHLECLVSRHERSLRMTVVKRQAQSPSGVSSEVEVLKALKSLFEHHK
                 ALDEQVRERLRAALERVTTLEEQLAGAHQQVICLLTLSLQLLEVQAGSPLCPTLFLVR
                 FLPAMAGSCLLTELLSLSLEEDTGRVEELQELLEKQNFELSQARERLVTLTTTVTELE
                 EDLGTARRDLIKSEELSSKHQRDLREALAQKEDMEERITTLEKRYLAAQREATSIHDL
                 NDKLENELANKESLHRQVEEKARHLQELLEVAEQKLQQTMRKAETLPEVEAELAQRIA
                 ALTKAEERHGNIEEHLRQLEGQLEEKNQELARVRQREKMNEDHNKRLSDTVDRLLSES
                 NERLQLHLKERMAALEEKVPRGAGLGCERLVLGVGRGEAGLLSEEIEKLRQEVDQLKG
                 RGGPFVDHHRSRSHMGSAADVRFSLGTTTHAPPGVHRRYSALREESAKVRGWRDLLRE
                 FGVNSADWETSPLPGMLAPAAGPAFDSDPEISDVDEDEPGGLVGSADVVSPSGHSDAQ
                 TLAMMLQEQLDAINEEIRLIQEEKESTELRAEEIETRVTSGSMEALNLKQLRKRGSIP
                 TSLTALSLASASPPLSGRSTPKLTSRSAAQDLDRMGVMTLPSDLRKHRRKLLSPVSRE
                 ENREDKATIKCETSPPSSPRTLRLEKLGHPALSQEEGKSALEDQGSNPSSSNSSQDSL
                 HKGAKRKGIKSSIGRLFGKKEKGRLIQLSRDGATGHVLLTDSEFSMQEPMVPAKLGTQ
                 AEKDRRLKKKHQLLEDARRKGMPFAQWDGPTVVSWLELWVGMPAWYVAACRANVKSGA
                 IMSALSDTEIQREIGISNALHRLKLRLAIQEMVSLTSPSAPPTSRTSSGNVWVTHEEM
                 ETLETSTKTDSEEGSWAQTLAYGDMNHEWIGNEWLPSLGLPQYRSYFMECLVDARMLD
                 HLTKKDLRVHLKMVDSFHRTSLQYGIMCLKRLNYDRKELEKRREESQHEIKDVLVWTN
                 DQVVHWVQSIGLRDYAGNLHESGVHGALLALDENFDHNTLALILQIPTQNTQARQVME
                 REFNNLLALGTDRKLDDGDDKVFRRAPSWRKRFRPREHHGRGGMLSASAETLPAGFRV
                 STLGTLQPPPAPPKKIMPEAHSHYLYGHMLSAFRD

[0381] Further analysis of the NOV16a protein yielded the following properties shown in Table 16B.

TABLE 16B
Protein Sequence Properties NOV16a
PSort     0.9800 probability located in nucleus; 0.3000 probability
analysis: located in microbody (peroxisome); 0.1000 probability located
          in mitochondrial matrix space;
          0.1000 probability located in lysosome (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0382] 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.

TABLE 16C
Geneseq Results for NOV16a
		NOV16a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAM38932	Human polypeptide SEQ ID NO	587 . . . 1253	666/667 (99%)	0.0
	2077 - Homo sapiens, 698 aa.	32 . . . 698	667/667 (99%)
	[WO200153312-A1, 26-JUL-2001]
AAM38933	Human polypeptide SEQ ID NO	587 . . . 1253	657/667 (98%)	0.0
	2078 - Homo sapiens, 689 aa.	32 . . . 689	658/667 (98%)
	[WO200153312-A1, 26-JUL-2001]
AAM40719	Human polypeptide SEQ ID NO	643 . . . 1253	609/611 (99%)	0.0
	5650 - Homo sapiens, 611 aa.	1 . . . 611	610/611 (99%)
	[WO200153312-A1, 26-JUL-2001]
AAM40718	Human polypeptide SEQ ID NO	643 . . . 1253	609/611 (99%)	0.0
	5649 - Homo sapiens, 611 aa.	1 . . . 611	610/611 (99%)
	[WO200153312-A1, 26-JUL-2001]
AAB94562	Human protein sequence SEQ ID	858 . . . 1237	371/380 (97%)	0.0
	NO: 15337 - Homo sapiens, 373	1 . . . 371	371/380 (97%)
	aa. [EP1074617-A2, 07-FEB-2001]

[0383] In a BLAST search of public sequence datbases, the NOV16a protein was found to have homology to the proteins shown in the BLASTP data in Table 16D.

TABLE 16D
Public BLASTP Results for NOV16a
		NOV16a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
O75334	LIPRIN-ALPHA2 - Homo	1 . . . 1220	831/1242 (66%)	0.0
	sapiens (Human), 1257 aa.	2 . . . 1227	982/1242 (78%)
S55553	LAR-interacting protein LIP1b -	1 . . . 1239	798/1274 (62%)	0.0
	human, 1202 aa.	2 . . . 1185	948/1274 (73%)
Q13136	LAR-INTERACTING	1 . . . 1239	798/1274 (62%)	0.0
	PROTEIN 1B - Homo sapiens	2 . . . 1185	947/1274 (73%)
	(Human), 1202 aa.
Q13135	LAR-INTERACTING	1 . . . 1234	798/1269 (62%)	0.0
	PROTEIN 1A - Homo sapiens	2 . . . 1180	945/1269 (73%)
	(Human), 1185 aa.
O75145	KIAA0654 PROTEIN - Homo	1 . . . 1240	736/1245 (59%)	0.0
	sapiens (Human), 1267 aa	75 . . . 1251	894/1245 (71%)
	(fragment).

[0384] PFam analysis predicts that the NOV16a protein contains the domains shown in the Table 16E.

TABLE 16E
Domain Analysis of NOV16a
		Identities/
Pfam	NOV16a	Similarities
Domain	Match Region	for the Matched Region	Expect Value
SAM	895 . . . 961	16/68 (24%)	0.84
		36/68 (53%)
SAM	1010 . . . 1074	22/68 (32%)	3.6e−11
		47/68 (69%)

Example 17

[0385] The NOV17 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 17A.

TABLE 17A
NOV17 Sequence Analysis
                 SEQ ID NO:33         1245 bp
NOV17a,          GCCCAAAAAGGCCATGTGCCTGTGCTGGCGTTCATAATGGAGGACCTGGAGGATGTGG
CG105638-01      CCCTGGACCACGTAGACAAGCTGGGGAGGACGGCGTTTCACAGGGCAGCTGAGCACGG
DNA Sequence     GCAGCTGGATGCTCTGGACTTCCTCGTGGGCTCTGGCTGTGACCACAATGTCAAAGAC
                 AAGGAGGGGAACACTGCCCTTCATCTGGCTGCTGGTCGGGGCCATATGGCTGTGCTGC
                 AGCGACTTGTGGACATCGGGCTGGACCTGGAGGAGCAGAATGCGGAAGGTCTGACTGC
                 CCTGCATTCGGCTGCTGGAGGATCCCACCCTGACTGTGTGCAGCTCCTCCTCAGGGCT
                 GGGAGCACCGTGAATGCCCTCACCCAGAAAAACCTAAGCTGCCTTCACTATGCAGCCC
                 TCAGTGGCTCGGAGGATGTGTCTCGGGTCCTCATCCACGCAGGAGGCTGCGCCAACGT
                 GGTTGATCATGGTGCCTCTCCTCTGCACCTCGCTGTGAGGCACAACTTCCCTGCCTTG
                 GTCCGGCTCCTCATCAACTCCGACAGTGACGTGAATGCCGTGGACAATAGGCAGCAGA
                 CGCCCCTTCACCTGGCTGCAGAGCACGCCTGGCAGGACATAGCAGATATGCTCCTCAT
                 TGCTGGGGTTGACTTAAACCTGAGAGATAAGCAGGGAAAAACCGCCCTGGCAGTGGCT
                 GTCCGCAGCAACCATGTCAGCCTGGTGGACATGATCATAAAAGCTGATCGTTTCTACA
                 GATGGGAGAAGACCACCCCAGTGATCCCTCTGGGAAGAGCTTGTCCTTTAAGCAGGAC
                 CATCGGCAGGAAACACAGCAGCTCCGTTCTGTGCTGTGGCGGCTGGCCTCCAGGTATC
                 TGCAGCCCCGTGAGTGGAAGAAGCTGGCATATTCCTGGGAGTTCACGGAGGCACATGT
                 CGACGCCATCGAGCAACAGTGGACAGGCACCAGGAGCTATCAGGAGCACGGCCACCGA
                 ATGCTGCTCATTTGGCTGCATGGCGTGGCCACGGCTGGTGAGAACCCCAGCAAAGCGC
                 TGTTCGAGGGCCTCGTGGCCATTGGCAGGAGGGACCTGGCTGGTAAGAGCGTACTCTG
                 CTGGGCTGCTTCTCAGGAGCTGGGTGGCCCCCACTGGAATGCAGCAGGGCCCTCCAAG
                 GGCTGCTCAGACAAGAATGCTGTGATGCTGGCTCTAGGCCTTCCAGATTCCTACCCCT
                 AGCCCTGCCCTCTTTTCCCTTGGGCAA
                 ORF Start: ATG at 37 ORF Stop: TGA at 1183
                 SEQ ID NO:34         382 aa MW at 40940.2 kD
NOV17a,          MEDLEDVALDHVDKLGRTAFHRAAEHGQLDALDFLVGSGCDHNVKDKEGNTALHLAAG
CG105638-01      RGHMAVLQRLVDIGLDLEEQNAEGLTALHSAAGGSHPDCVQLLLRAGSTVNALTQKNL
Protein Sequence SCLHYAALSGSEDVSRVLIHAGGCANVVDHGASPLHLAVRHNFPALVRLLINSDSDVN
                 AVDNRQQTPLHLAAEHAWQDIADMLLIAGVDLNLRDKQGKTALAVAVRSNHVSLVDMI
                 IKADRFYRWEKTTPVIPLGRACPLSRTIGRKHSSSVLCCGGWPPGICSPVSGRSWHIP
                 GSSRRHMSTPSSNSGQAPGAIRSTATECCSFGCMAWPRLVRTPAKRCSRASWPLAGGT
                 WLVRAYSAGLLLRSWVAPTGMQQGPPRAAQTRML

[0386] Further analysis of the NOV17a protein yielded the following properties shown in Table 17B.

TABLE 17B
Protein Sequence Properties NOV17a
PSort     0.6500 probability located in cytoplasm;
analysis: 0.2403 probability located in lysosome (lumen);
          0.1000 probability located in mitochondrial matrix space;
          0.0000 probability located in endoplasmic reticulum
          (membrane)
SignalP   No Known Signal Sequence Predicted
analysis:

[0387] 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 17C.

TABLE 17C
Geneseq Results for NOV17a
		NOV17a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAU19570	Human diagnostic and therapeutic	14 . . . 156	121/144 (84%)	3e−60
	polypeptide (DITHP) #156 -	19 . . . 162	124/144 (86%)
	Homo sapiens, 162 aa.
	[WO200162927-A2, 30-AUG-2001]
AAM93683	Human polypeptide, SEQ ID NO:	1 . . . 113	113/113 (100%)	8e−60
	3580 - Homo sapiens, 129 aa.	1 . . . 113	113/113 (100%)
	[EP1130094-A2, 05-SEP-2001]
AAO02579	Human polypeptide SEQ ID NO	16 . . . 243	83/231 (35%)	1e−33
	16471 - Homo sapiens, 266 aa.	21 . . . 251	128/231 (54%)
	[WO200164835-A2, 07-SEP-2001]
AAU03539	Human protein kinase #39 - Homo	5 . . . 234	78/232 (33%)	6e−28
	sapiens, 832 aa. [WO200138503-	574 . . . 804	127/232 (54%)
	A2, 31-MAY-2001]
ABB53291	Human polypeptide #31 - Homo	5 . . . 234	77/232 (33%)	1e−27
	sapiens, 784 aa. [WO200181363-	526 . . . 756	127/232 (54%)
	A1, 01-NOV-2001]

[0388] In a BLAST search of public sequence datbases, the NOV17a protein was found to have homology to the proteins shown in the BLASTP data in Table 17D.

TABLE 17D
Public BLASTP Results for NOV17a
		NOV17a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9GKW8	HYPOTHETICAL 40.3 KDA	1 . . . 243	229/243 (94%)	e−131
	PROTEIN - Macaca fascicularis	1 . . . 243	238/243 (97%)
	(Crab eating macaque)
	(Cynomolgus monkey), 366 aa.
AAH27350	HYPOTHETICAL 14.0 KDA	15 . . . 113	76/105 (72%)	5e−32
	PROTEIN - Homo sapiens	13 . . . 117	82/105 (77%)
	(Human), 133 aa (fragment).
Q8YTG9	HYPOTHETICAL PROTEIN	22 . . . 233	75/214 (35%)	2e−27
	ALL2748 - Anabaena sp. (strain	10 . . . 223	124/214 (57%)
	PCC 7120), 426 aa.
Q96KH0	PROBABLE DUAL-	5 . . . 234	78/232 (33%)	2e−27
	SPECIFICITY SER/THR/TYR	526 . . . 756	127/232 (54%)
	KINASE - Homo sapiens
	(Human), 784 aa.
Q9NTA1	HYPOTHETICAL 42.9 KDA	5 . . . 234	78/232 (33%)	2e−27
	PROTEIN - Homo sapiens	139 . . . 369	127/232 (54%)
	(Human), 397 aa (fragment).

[0389] PFam analysis predicts that the NOV17a protein contains the domains shown in the Table 17E.

TABLE 17E
Domain Analysis of NOV17a
			Identities/
			Similarities
	Pfam	NOV17a Match	for the Matched	Expect
	Domain	Region	Region	Value
	ank	15 . . . 47	14/33 (42%)	2.7e−06
			25/33 (76%)
	ank	48 . . . 80	13/33 (39%)	3.3e−06
			25/33 (76%)
	ank	81 . . . 113	16/33 (48%)	2.2e−07
			24/33 (73%)
	ank	114 . . . 146	11/33 (33%)	0.0005
			26/33 (79%)
	ank	147 . . . 178	15/33 (45%)	0.00017
			26/33 (79%)
	ank	179 . . . 211	16/33 (48%)	2.6e−06
			26/33 (79%)

Example 18

[0390] The NOV18 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 18A.

TABLE 18A
NOV18 Sequence Analysis
                 SEQ ID NO:35        5650 bp
NOV18a,          ATGGCCCCTTCTGAGACTGCTCGGAAGTGGGAGAGGATGCTTGCCCTTACGGGTGTTC
CG105671-01      TGCCCCTGAGACTGGCGCCCCTTGGTGCTCCCTCTGTTCCCTCCCAGATCTTGGGAGA
DNA Sequence     AGCACGGACATCTCTGTTTCTGCTTTTGGTCCCCGAACGCAGTTACGCGCCCACTGGC
                 TCCCTGTCTCTGGCGCTTCTGGGCACGGGGGAGCTGGGGCGGCCCCGCCTGCGCACGG
                 CGGACAAGCTGACCGGGTCTCTGAGGCGCGGGGGGAGATGCCTGAAGCGGCAGGGCGG
                 CGGCGTGGGCACCATCCTGAGCAATGTGCTCAAGAAGCGCAGCTGCATTTCCCGGACC
                 GCGCCCCGGCTGCTGTGCACCCTGGAGCCGGGCCGGGGAGCTCTGGGGAAAGTCCGCG
                 TGCCACCTGGTGCGGGGCACCGCGTTGGCACCTGCAGGGAGCGATTGGTCTGGAAGGG
                 CTCGCAGGAAGCCAGACCTTGCGAGAGGTGTGTGGGGGCGGAGAGTGGCACAGGTTTG
                 ACACTGCAGGTCGGAGGAGGAAGACAGTGGCTGCAAAGGCAAAATCGGGTGTTATTTT
                 CCCAAGAGTCCCTTCAGCGTGAGTGCCGGGGTCAGCTCGAACTGGAGCCTGTAATTTG
                 TGAGTGCGAGTGGGGAGCAGCAGGAGATCCTTTTCATAGACTGCATAACTCCGTGTCG
                 GCTCCATCACCCGGCATCCCTCCCCGGGATTTTAAGAGCCTGGCCCTAGCGCGGGCTC
                 CTGGGCACGGAGGTTTCTGGCAAGGAGTGGCTGCAGAGGGAGTTGGCTGTACTCTCAC
                 TGGTGCTTGGCGCTCACCTGTTCCCTGGAGTGGCACCGGCTGCGTTCCAGGCGGGTTC
                 ACGGTCCCCGGCCCCCGCCCCCCAGCGCCAGCGCCTTGGGGACCTGCTGTAGAGCCGC
                 AGGAGAATCGAGCTGCAGAGTCCCTGCCTGCTTGCAGGCTGTGTCACAGAAGAGAACA
                 TGGCAGAACAGTATGCTCAGGAGTTGATACCAAGTTGAAATTCACTCTTGAGCCATCT
                 TTAGGTCAAAATGGTTTTCAGCAGTGGTACGATGCTCTCAAGGCAGTTGCCAGGCTAT
                 CCACAGGAATACCAAAGGAATGGAGGAGAAAGGTTTGGTTGACCTTGGCAGATCATTA
                 TTTGCACAGTATAGCCATTGACTGGGACAAAACCATGCGCTTCACTTTCAATGAAAGG
                 AGTAATCCTGATGATGACTCCATGGGAATTCAGATAGTCAAGGACCTTCACCGCACAG
                 GCTGTAGTTCTTACTGTGGCCAGGAGGCTGAGCAGGACAGGGTTGTGTTGAAGCGGGT
                 GCTGCTGGCCTATGCCCGATGGAACAAAACTGTTGGGTACTGCCAAGGCTTTAACATC
                 CTGGCTGCACTAATTCTGGAAGTGATGGAAGGCAATGAAGGGGATGCCCTGAAAATTA
                 TGATTTACCTTATTGATAAGGTACTTCCCGAAAGCTATTTCGTCAATAATCTCCGGGC
                 ATTGTCTGTGGATATGGCTGTCTTCAGAGACCTTTTAAGAATGAAGCTGCCGGAATTA
                 TCTCAGCACCTGGATACTCTTCAGAGAACTGCAAACAAAGAAAGTGGAGGTGGATATG
                 AGCCCCCACTTACAAATGTCTTCACGATGCAGTGGTTTCTGACTCTCTTTGCCACATG
                 CCTCCCTAATCAGACCGTTTTAAAGATCTGGGATTCAGTCTTCTTTGAAGGTTCAGAA
                 ATCATCCTAAGGGTGTCGCTGGCTATCTGGGCAAAATTAGGAGAGCAGATAGAATGTT
                 GTGAAACAGCAGATGAATTCTACAGCACCATGGGGCGCCTTACCCAGGAGATGCTAGA
                 GAATGATCTTCTGCAAAGCCATGAACTCATGCAGACTGTTTATTCCATGGCTCCGTTC
                 CCTTTCCCACAATTGGCAGAGTTGAGGGAAAAATACACCTACAACATTACACCGTTCC
                 CAGCCACAGTTAAACCCACCTCAGTTTCTGGACGACATAGTAAGGCCAGAGACAGTGA
                 TGAAGAGAATGACCCAGACGATGAGGATGCTGTCGTTAATGCAGTGGGGTGTCTTGGA
                 CCTTTTAGTGGGTTCCTGGCTCCTGAACTGCAGAAGTACCAAAAACAAATTAAAGAGC
                 CAAATGAGGAGCAGAGTCTGAGATCTAATAACATTGCAGAGCTGAGTCCAGGAGCAAT
                 CAATTCCTGTCGAAGTGAATACCATGCAGCTTTTAACAGTATGATGATGGAACGCATG
                 ACCACAGATATCAATGCACTGAAGCGGCAGTACTCTCGAATTAAAAAGAAGCAACAGC
                 AGCAGGTTCATCAGGTGTACATCAGGGCAGACAAAGGGCCAGTGACCAGCATTCTCCC
                 GTCTCAGGTAAACAGTTCTCCAGTTATAAACCACCTTCTTTTAGGAAAGAAGATGAAA
                 ATGACTAACAGAGCTGCCAAGAATGCTGTCATCCACATCCCTGGTCACACAGGAGGGA
                 AAATATCTCCTGTCCCCTACGAAGACCTTAAGACGAAGCTCAACTCCCCGTGGCGAAC
                 TCACATCCGAGTCCACAAAAAGAACATGCCAAGGACCAAGAGTCATCCGGGCTGTGGG
                 GACACCGTAGGGCTGATAGATGAGCAGAACGAGGCCAGCAAGACCAATGGGCTGGGGG
                 CAGCAGAGGCATTCCCCTCTGGTTGTACAGCGACAGCTGGGAGAGAAGGCAGCAGCCC
                 TGAAGGCAGTACCAGGAGGACGATCGAGGGGCAGTCTCCGGAGCCGGTGTTCGGAGAT
                 GCTGATGTGGATGTGTCTGCAGTTCAGGCGAAGTTGGGAGCCCTGGAACTGAACCAGA
                 GGGATGCTGCAGCTGAAACTGAGCTCAGGGTGCACCCACCCTGCCAGCGGCACTGCCC
                 AGAGCCGCCGAGTGCACCCGAAGAAAACAAAGCCACCAGCAAAGCTCCCCAAGGCAGC
                 AACTCAAAAACCCCCATCTTTAGCCCTTTTCCCAGCGTCAAGCCCCTGCGGAAATCTG
                 CTACTGCCAGGAACTTGGGATTATATGGCCCTACAGAAAGAACCCCAACTGTGCACTT
                 TCCTCAAATGAGTAGGAGCTTCAGCAAACCCGGCGGTGGAAACAGTGGCACTAAAAAA
                 CGATGATGTCTCCCCGAAACTTTGTATCTGGACTCACCTTTTCACAGTAGTATAAGGG
                 TTGCAGCTGAATGGCTCTAAAAGAGTTTTATTTGTCCAGTGAAAATGAATAGGTTCAG
                 GGATGAGCAACAGCCCATAAAAAATGGGAACTGGAAGTTTTATAATAGGAGTTAGAAC
                 AGGGCTGTTTTCCCAGCTACTTGCTAACTGACGAAGTGGATTCTTGTGGCAAAATAAA
                 TATTGTGGTTTTATAGTGTGAAGTTTTCCCAATTTTTCATTGTGAGCTGTTTAAAAAA
                 GACTATATCTAGATTGTTAACTCTCGTCCATCCTTCTGTTCTGGGGGCCTTCAGAGTC
                 CCTGTGACAGCACCCCCAAACCTTCCAGTTCTCTGGGTGTTACTAATACTCAAGCATG
                 CACATACCAGCTTGCTAGGACAGAAACTGTAAAAAGAAAGTAAGTTTCTTCGTTACAA
                 AAAACTTCCTGATTTTCCTTTTCATGCTTTACGGAGGGGATTGTGTCGTGTGAGATTT
                 CCCACAGTACCAGTTTCAAATTTTTTTTTATTCTTATGCTAAATCATAGGAGAAAAAT
                 CTAGATGGCCTTTCTTTAACTGTCTATTTCTACCTGCAAAATGAAGAAAACCTTTCAT
                 CTGTTGAAATTTCAATCGATAACCCAGCTGAAGATCTTATGCACAGGACACACTTGGC
                 ATATGCTTTACGCAGTTGCTCCGGACAGCTTGCTCGCGCCACTGAGCTTTTCCTGAGG
                 TTTGTGTTCGCCTCTCAAGGAGAGCTTTGATCCTCAGTGGTACGGATGACTTGATGGG
                 CTCCATGCGGAGCCTGGCCTGCATCCCCCACCACACAGCTCACTCACCCACCAGCTCT
                 AGACTGCAGACGCACAAGGCCTCTGCTCAGAAGCCAGAACACAGCACCTGTGACTCTG
                 TTACTTGAATTTTGTGCTTTTTGATTGGAGTCCTTTGTTGAGTACTTTGTTAATTGAA
                 CACTGCCTTTCTCTGGAGAAGGCCCCAGTGCTTTCTAGCTCCCTCTCACTCCTGCCCT
                 TTCTAGCTCTCTCTCACCCAGCGGGTCAGGGATAGCACCTCTTGTCTCCACTATGCAG
                 ATGGGAACTCTGAGCCACACAGAGGTGAAGTAGCACTTCAGTTACTCAAGGTCAGTAC
                 TCTCGGTATTCCAAGTGACTTAGCCACATTTCCTTCAGTGCAATAGGTGGGTTTAATG
                 CTCTTTGTACACAGATGTATTGGCTACATAGCGTGTAAAAACCAAGACTGGGAAGCCA
                 TTCACTAAAATCCCTCCTGACTCAAAGGACCTGTCTCCAGATGGTACAGAGTCCCTTG
                 ATGGCATTTTACAAAACCAGCTCTGACTTCCTTATCCTGAACAGGGAGTTTATTTTAA
                 AAATGCTTCATGCACCTGTTATTTGGCTGAACAGAAGGCTCACTCCTCAATCCCCTTC
                 TCCTCGCCATCATTAGAGGAATAGACTCAGCCTTCATGTTTGTCTCTGGAAGACGATT
                 GGCGATACTTGCAGGAATATTGTTGATGCAGCCAATATTAATTTGAGCTAATGGATTG
                 TTAATTCTGAAACGAAAACTGTAACTGTAGAGCAGGCTTTTACTATGAGAGGTACTAC
                 TTTTTATAATAGAGAATGTGGTTGTGTGGGCTTTTTTTGAACAGAAAACACAACAATG
                 ACCTATACCGTGAGAAAAGCCATTTTATCTTCTTCGTGGTATTTTTACCCCCAAAGGA
                 ACTGAAGATGGAAAATATGACTAATAAGTTATTGCAGTTTTGGTCTTGAATTCTGTGC
                 CATCTGAAGTTAGCATCCAGCTTCTTAAAAAGCAGCCACGCCTACAGCCTGTTTTTTG
                 GGAAGGCTGTAGGTGGAGAGATGGGCTTATTTTGCATACCACCCTCAGGGCCCAGAGA
                 CCCACTGCATTTTCCAAAGTTAAGCATGACACCATTTTCTTCCATCAGCTAAACTTTA
                 CAGATAATAGTGTTTCCACCTCATATCCTTTTCTTTGCCCCTTCTCAAATGAGTCAGA
                 ATAGTCATGTTCCCCTTGAGGGATGTCTGACTTGAATGGAGAATTGTTCTTTCCTCTC
                 TTGAATCAGCTCACTAGCTCCCTGATGGTCTGGGTTCAAGGAAATGGTTAATGAGGTA
                 GAGGCCACTTATACAAGTCCTTGGGATTGTACCATTGCTGTCCACAAACTTAGTATCA
                 ACAACACATGCTGTGCCCTGTGAACACTCTCCTCTCACCTATTTCCAGGGTTGGTCTT
                 CCTGAGAAGGGGATGGATGAGGTAACACACAGTTTGGGATACGTATCTGTTGAATGAA
                 TGAATAAGTGAAAGGATAATAGTCCTCTGAGGTAAAAATGGCCTTGTCAGAATTTTGA
                 AAATCCAACAGATTCCTATTAAAGCACTCTGTGTACCAATAACATGCATGCATTGTAC
                 CAAGTAATCACAATGTGAATTGGTCAATTTATGAGCCTTGCCTACTTTAGAAAATAAA
                 GAAACCTGCAGTAGCCTCTACCAC
                 ORF Start: ATG at 1 ORF Stop: TGA at 3136
                 SEQ ID NO:36        1045 aa MW at 114769.8 kD
NOV18a,          MAPSETARKWERMLALTGVLPLRLAPLGAPSVPSQILGEARTSLFLLLVPERSYAPTG
CG105671-01      SLSLALLGTGELGRPRLRTADKLTGSLRRGGRCLKRQGGGVGTILSNVLKKRSCISRT
Protein Sequence APRLLCTLEPGRGALGKVRVPPGAGHRVGTCRERLVWKGSQEARPCERCVGAESGTGL
                 TLQVGGGRQWLQRQNRVLFSQESLQRECRGQLELEPVICECEWGAAGDPFHRLHNSVS
                 APSPGIPPRDFKSLALARAPGHGGFWQGVAAEGVGCTLTGAWRSPVPWSGTGCVPGGF
                 TVPGPRPPAPAPWGPAVEPQENRAAESLPACRLCHRREHGRTVCSGVDTKLKFTLEPS
                 LGQNGFQQWYDALKAVARLSTGIPKEWRRKVWLTLADHYLHSIAIDWDKTMRFTFNER
                 SNPDDDSMGIQIVKDLHRTGCSSYCGQEAEQDRVVLKRVLLAYARWNKTVGYCQGFNI
                 LAALILEVMEGNEGDALKIMIYLIDKVLPESYFVNNLRALSVDMAVFRDLLRMKLPEL
                 SQHLDTLQRTANKESGGGYEPPLTNVFTMQWFLTLFATCLPNQTVLKIWDSVFFEGSE
                 IILRVSLAIWAKLGEQIECCETADEFYSTMGRLTQEMLENDLLQSHELMQTVYSMAPF
                 PFPQLAELREKYTYNITPFPATVKPTSVSGRHSKARDSDEENDPDDEDAVVNAVGCLG
                 PFSGFLAPELQKYQKQIKEPNEEQSLRSNNIAELSPGAINSCRSEYHAAFNSMMMERM
                 TTDINALKRQYSRIKKKQQQQVHQVYIRADKGPVTSILPSQVNSSPVINHLLLGKKMK
                 MTNRAAKNAVIHIPGHTGGKISPVPYEDLKTKLNSPWRTHIRVHKKNMPRTKSHPGCG
                 DTVGLIDEQNEASKTNGLGAAEAFPSGCTATAGREGSSPEGSTRRTIEGQSPEPVFGD
                 ADVDVSAVQAKLGALELNQRDAAAETELRVHPPCQRHCPEPPSAPEENKATSKAPQGS
                 NSKTPIFSPFPSVKPLRKSATARNLGLYGPTERTPTVHFPQMSRSFSKPGGGNSGTKK
                 R

[0391] Further analysis of the NOV18a protein yielded the following properties shown in Table 18B.

TABLE 18B
Protein Sequence Properties NOV18a
PSort     0.4865 probability located in mitochondrial matrix space;
analysis: 0.3000 probability located in microbody (peroxisome);
          0.1977 probability located in mitochondrial inner membrane;
          0.1977 probability located in mitochondrial
          intermembrane space
SignalP   Cleavage site between residues 32 and 33
analysis:

[0392] 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.

TABLE 18C
Geneseq Results for NOV18a
		NOV18a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
ABG05609	Novel human diagnostic protein #	322 . . . 1045	715/727 (98%)	0.0
	5600 - Homo sapiens, 770 aa.	44 . . . 770	717/727 (98%)
	[WO200175067-A2, 11-OCT-2001]
AAM39447	Human polypeptide SEQ ID NO	322 . . . 1045	715/727 (98%)	0.0
	2592 - Homo sapiens, 761 aa.	35 . . . 761	717/727 (98%)
	[WO200153312-A1, 26-JUL-2001]
ABG05609	Novel human diagnostic protein #	322 . . . 1045	715/727 (98%)	0.0
	5600 - Homo sapiens, 770 aa.	44 . . . 770	717/727 (98%)
	[WO200175067-A2, 11-OCT-2001]
AAM41234	Human polypeptide SEQ ID NO	322 . . . 1044	712/726 (98%)	0.0
	6165 - Homo sapiens, 798 aa.	44 . . . 769	714/726 (98%)
	[WO200153312-A1, 26-JUL-2001]
AAM41233	Human polypeptide SEQ ID NO	322 . . . 1044	712/726 (98%)	0.0
	6164 - Homo sapiens, 798 aa.	44 . . . 769	714/726 (98%)
	[WO200153312-A1, 26-JUL-2001]

[0393] In a BLAST search of public sequence datbases, the NOV18a protein was found to have homology to the proteins shown in the BLASTP data in Table 18D.

TABLE 18D
Public BLASTP Results for NOV18a
		NOV18a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9Y219	KIAA0984 PROTEIN - Homo	318 . . . 1045	728/728 (100%)	0.0
	sapiens (Human), 728 aa	1 . . . 728	728/728 (100%)
	(fragment).
Q9D579	4930505D03RIK PROTEIN -	610 . . . 1045	377/440 (85%)	0.0
	Mus musculus (Mouse), 440 aa.	1 . . . 440	393/440 (88%)
Q9VH10	CG3996 PROTEIN - Drosophila	354 . . . 819	183/496 (36%)	2e−81
	melanogaster (Fruit fly), 3111 aa.	84 . . . 520	259/496 (51%)
Q9NSH4	HYPOTHETICAL 54.4 KDA	367 . . . 647	92/288 (31%)	2e−26
	PROTEIN - Homo sapiens	162 . . . 422	143/288 (48%)
	(Human), 468 aa.
Q9H6A2	CDNA: FLJ22452 FIS, CLONE	367 . . . 647	92/288 (31%)	2e−26
	HRC09667 - Homo sapiens	404 . . . 664	143/288 (48%)
	(Human), 710 aa.

[0394] PFam analysis predicts that the NOV18a protein contains the domains shown in the Table 18E.

TABLE 18E
Domain Analysis of NOV18a
		Identities/
Pfam		Similarities	Expect
Domain	NOV18a Match Region	for the Matched Region	Value
TBC	367 . . . 600	73/342 (21%)	1.8e−26
		156/342 (46%)

Example 19

[0395] The NOV19 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 19A.

TABLE 19A
NOV19 Sequence Analysis
                 SEQ ID NO:37        868 bp
NOV19a,          AATGGCCACAGCCAGCTATCTGTATGGGCGGGGCTGCCCTGGAGATGCAGGGCAAGCG
CG105778-01      CCAGGAACCCCTCCGGGTAGCTACTACCTTGGACCCCCCAGTAGTGGAGGGCAGTATG
DNA Sequence     GCAGCGTGCTACCCCCTGGTGGTGGCTATGGGGGTCCTGCCCCTGGAGGGCCTTATGG
                 ACCACCAGCTGGTAGAGGGCCCTATGGACACCTCAATCCTGGGATGTTCCCCTCTGGA
                 ACTCCAGGAGGACCAAATGATGGTACAGCTCCAGGGGGCCCCTATGGTCAGCCACCTC
                 CAAATTCCTACGGTGCCCAGCAGCCCAGGCCTCATGGACAGGGTGGCTCCCCTCCCAA
                 TATGGATGAGGCCTACTCCTGGTTCCAGTCGGTGGACTCTGATCACAGTGGCTTTATC
                 TCCATGAAGGAGGTGAAGCAGGCTCTGGTCAACTGCAACTGGTCCTTGTTCAATGATG
                 AGACCTGCCTCATGATGATAAACATGTTTGACAAGACCAAATCAGGCCACATAAATGT
                 CTACGGCTTCTCAGCCCTGTGGAAATTCATCCAGCAGTGGAAGCAGCTCTTCCAGCAG
                 TATGACTGGGACAACTCAGGCTCCATTAGCTACACAGAGCTGCAGCAAGCTCTGTCCC
                 AAATGGGCTACAACCTGAGCCCCCAGTTCACCCAGCTACTGGTCTCCAGCTACTGCCC
                 ACGCTCTGTCAATCCTGCCAGACAGCTTGATTGCTTCATCCAGGTGTGCACCCAGCTG
                 CAGATGCCGACAGAGGCCTTCCGGGAGAAGGACACAGCTGTACAAGGCAACATTCGGC
                 TCAGCTTCAAGGACGTCGTCACCATGACAGCTCGGATGCTATGACCCAACCCATCT
                 ORF Start: ATG at 2 ORF Stop: TGA at 854
                 SEQ ID NO:38        284 aa MW at 30581.0 kD
NOV19a,          MATASYLYGRGCPGDAGQAPGTPPGSYYLGPPSSGGQYGSVLPPGGGYGGPAPGGPYG
CG105778-01      PPAGRGPYGHLNPGMFPSGTPGGPNDGTAPGGPYGQPPPNSYGAQQPRPHGQGGSPPN
Protein Sequence MDEAYSWFQSVDSDHSGFISMKEVKQALVNCNWSLFNDETCLMMINMFDKTKSGHINV
                 YGFSALWKFIQQWKQLFQQYDWDNSGSISYTELQQALSQMGYNLSPQFTQLLVSSYCP
                 RSVNPARQLDCFIQVCTQLQMPTEAFREKDTAVQGNIRLSFKDVVTMTARML

[0396] Further analysis of the NOV19a protein yielded the following properties shown in Table 19B.

TABLE 19B
Protein Sequence Properties NOV19a
PSort     0.5472 probability located in microbody (peroxisome);
analysis: 0.4500 probability located in cytoplasm;
          0.3024 probability located in lysosome (lumen);
          0.1000 probability located in mitochondrial matrix space
SignalP   No Known Signal Sequence Predicted
analysis:

[0397] 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.

TABLE 19C
Geneseq Results for NOV19a
		NOV19a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAB87556	Human PRO3573 - Homo sapiens,	4 . . . 284	246/283 (86%)	e−147
	284 aa. [WO200116318-A2, 08-MAR-2001]	2 . . . 284	257/283 (89%)
AAB92943	Human protein sequence SEQ ID	4 . . . 284	246/283 (86%)	e−147
	NO: 11614 - Homo sapiens, 284 aa.	2 . . . 284	257/283 (89%)
	[EP1074617-A2, 07-FEB-2001]
AAU29141	Human PRO polypeptide sequence #	4 . . . 284	246/283 (86%)	e−147
	118 - Homo sapiens, 284 aa.	2 . . . 284	257/283 (89%)
	[WO200168848-A2, 20-SEP-2001]
AAY44254	Human apoptosis linked gene-2	4 . . . 284	246/283 (86%)	e−147
	like protein - Homo sapiens, 284	2 . . . 284	257/283 (89%)
	aa. [WO9961459-A1, 02-DEC-1999]
AAY82706	Human apoptosis related protein	4 . . . 284	246/283 (86%)	e−147
	ABP32 SEQ ID NO: 2 - Homo	2 . . . 284	257/283 (89%)
	sapiens, 284 aa. [JP2000083672-A,
	28-MAR-2000]

[0398] In a BLAST search of public sequence datbases, the NOV19a protein was found to have homology to the proteins shown in the BLASTP data in Table 19D.

TABLE 19D
Public BLASTP Results for NOV19a
		NOV19a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9UBV8	PEFLIN (SIMILAR TO PEF	4 . . . 284	246/283 (86%)	e−146
	PROTEIN WITH A LONG N-	2 . . . 284	257/283 (89%)
	TERMINAL HYDROPHOBIC
	DOMAIN) - Homo sapiens
	(Human), 284 aa.
Q8VCT5	RIKEN CDNA 2600002E23 GENE -	4 . . . 284	211/283 (74%)	e−119
	Mus musculus (Mouse), 275 aa.	2 . . . 275	225/283 (78%)
Q9D934	2600002E23RIK PROTEIN - Mus	4 . . . 284	211/283 (74%)	e−119
	musculus (Mouse), 275 aa.	2 . . . 275	225/283 (78%)
Q9CYW8	2600002E23RIK PROTEIN - Mus	4 . . . 257	186/255 (72%)	e−106
	musculus (Mouse), 268 aa.	2 . . . 247	199/255 (77%)
Q9V5M1	CG17765 PROTEIN (GH27120P) -	81 . . . 279	81/199 (40%)	1e−34
	Drosophila melanogaster (Fruit fly),	6 . . . 193	111/199 (55%)
	199 aa.

[0399] PFam analysis predicts that the NOV19a protein contains the domains shown in the Table 19E.

TABLE 19E
Domain Analysis of NOV19a
		Identities/
Pfam		Similarities	Expect
Domain	NOV19a Match Region	for the Matched Region	Value
efhand	119 . . . 147	11/29 (38%)	0.0098
		22/29 (76%)
efhand	186 . . . 214	10/29 (34%)	2.8e−05
		25/29 (86%)

Example 20

[0400] The NOV20 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 20A.

TABLE 20A
NOV20 Sequence Analysis
                 SEQ ID NO:39        1491 bp
NOV20a,          ATGCCAGATTATAGCAAAAGGATGTTGAGGGAGCAATATGAAAGCAAGCCTGAGAGTC
CG105796-01      CTGGAGAGAAGCAACCCCATGGGTATGAACTTGAGATGATTCACTTTCCTAAAAGCCT
DNA Sequence     CTTTGAGCTGAAAAAGGAAACGCGTTTTATGGCACTGCCACCTCTGGTCACCCACCCC
                 GAGGTGTGGCAGACCTGGACAGACAGCATGACCGAGGGCCAGGCTGGTGAAGTCAAAC
                 CTACCACTCAGGAAGGAGACCCAGCCCTTCTCCAGACAGAGTTCAAATTTTCCTCAGC
                 TGAGAAATGGGGTGGGGGCAAATGGTCTAAGGTTCTGGGAACCTCTAAGTCAGATGAG
                 GGAGAGGCCCTGAGGGTCAGCCGCACGCCTGAGAGGCAGGACAGACCCAAAGGTGGGC
                 AACCTGAGCACATCAGGGTACTCAAGCAGCTGGCCTCTGGGGTAGCAGCCCTGGGTGT
                 GAGAAGCAGGACTCAGAATCTAAGCCAACCCTCCACAGGAATCCCCTCTGGAGAGCCC
                 GGGCACTCTGCAGGAGGGGCAGCAGGCAGCAGGTGCACCAGAAGCATGTTTCGCAAGG
                 TGCCCAATAATGCCTCTGCTCTGATAGGCAGCGAGTTGGAACATGGATGCAGTAGGCA
                 GGGTGGTGGCTGCTCCCCACAGCCAGGAGTCCAGCCCAGCACCCACCTGAGTCCACCT
                 GAGTCCTGCTCAATTGGGTCATCCGTGCTCTGGGCCCTCTGGTCCCACCCACAGAGGG
                 AGGGCTTTGGGGTGACCAGGCTCGCCTGGTCACGTGTCCTTCACTTTCCTCTGAGTCT
                 CCCTCTTTCCAAGCCGCCTCCACTCTACTGGACACACTGTCCCTTAAGACACCAGAGT
                 ACAGAAGCTCAAGTCCCTGCACCTCACCTTTACTCCCAGACATGGGAGGGACATGACA
                 TAAAGACCCAAACGCCACTTGGCAAGAGTTCTGGGGAAGCTGCATGTAAGCTGGCTAT
                 TGAATGTGGCTCTGAGCTGAGACCTCTCCTTGAAGCTCCAGACCAGGAGCCAGCTGCC
                 AGCTGGACCCCGCCATTTGGTGCCTCAGAGAAACCTTGCACTCTTGTGGGACAGCTGC
                 ACAAGGGCCCAGCATGTCTGTGTGTTTACCCAGGGAACTGCCGCATGGCTCATGCTGA
                 GCAGAAGCTGATGGACGACCTTCTGAACAAAACCCGTTACAACAACCTGATCTGCCCA
                 GCCACCAGCTCCTCACAGCTCATCTCCATCGAGACAGAGCTCTCCCTGGCGCAGTGCA
                 TCAGTGTGCTTGCTCAACAGGTGACCTTACAGGCTCCCTACTTGTTGGGGGAAATAAG
                 AACCAAACTGCGGGAACTGACGGGTACAGTGGCCCAGGAGGAAGCACAGCTGAAGGAT
                 GCGAAGGGCAGTAGAGTTGTGTATGCTCCACCCCCTCTCTCCACAGTCAGATCGGAAA
                 GAAGGGGGCTTTCAGCCAGGCTCGCCCAGACTGGGGTCTGA
                 ORF Start: ATG at 1 ORF Stop: TGA at 1489
                 SEQ ID NO:40        496 aa MW at 54061.8 kD
NOV20a,          MPDYSKRMLREQYESKPESPGEKQPHGYELEMIHFPKSLFELKKETRFMALPPLVTHP
CG105796-01      EVWQTWTDSMTEGQAGEVKPTTQEGDPALLQTEFKFSSAEKWGGGKWSKVLGTSKSDE
Protein Sequence GEALRVSRTPERQDRPKGGQPEHIRVLKQLASGVAALGVRSRTQNLSQPSTGIPSGEP
                 GHSAGGAAGSRCTRSMFRKVPNNASALIGSELEHGCSRQGGGCSPQPGVQPSTHLSPP
                 ESCSIGSSVLWALWSHPQREGFGVTRLAWSRVLHFPLSLPLSKPPPLYWTHCPLRHQS
                 TEAQVPAPHLYSQTWEGHDIKTQTPLGKSSGEAACKLAIECGSELRPLLEAPDQEPAA
                 SWTPPFGASEKPCTLVGQLHKGPACLCVYPGNCRMAHAEQKLMDDLLNKTRYNNLICP
                 ATSSSQLISIETELSLAQCISVLAQQVTLQAPYLLGEIRTKLRELTGTVAQEEAQLKD
                 AKGSRVVYAPPPLSTVRSERRGLSARLAQTGV

[0401] Further analysis of the NOV20a protein yielded the following properties shown in Table 20B.

TABLE 20B
Protein Sequence Properties NOV20a
PSort     0.4500 probability located in cytoplasm;
analysis: 0.3000 probability located in microbody (peroxisome);
          0.1000 probability located in mitochondrial matrix
          space; 0.1000 probability located in lysosome (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0402] 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.

TABLE 20C
Geneseq Results for NOV20a
		NOV20a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAE10098	Human ion channel-73 (ion73)	379 . . . 432	49/54 (90%)	5e−21
	protein - Homo sapiens, 54 aa.	1 . . . 54	53/54 (97%)
	[WO200168849-A2, 20-SEP-2001]
AAU83503	Novel human ion channel ion-103 -	379 . . . 428	45/50 (90%)	3e−17
	Homo sapiens, 50 aa.	1 . . . 50	47/50 (94%)
	[WO200202639-A2, 10-JAN-2002]
AAE10099	Human ion channel-74 (ion74)	379 . . . 428	45/50 (90%)	3e−17
	protein - Homo sapiens, 50 aa.	1 . . . 50	47/50 (94%)
	[WO200168849-A2, 20-SEP-2001]
ABG05709	Novel human diagnostic protein #	95 . . . 133	39/39 (100%)	1e−15
	5700 - Homo sapiens, 464 aa.	94 . . . 132	39/39 (100%)
	[WO200175067-A2, 11-OCT-2001]
ABG05709	Novel human diagnostic protein #	95 . . . 133	39/39 (100%)	1e−15
	5700 - Homo sapiens, 464 aa.	94 . . . 132	39/39 (100%)
	[WO200175067-A2, 11-OCT-2001]

[0403] In a BLAST search of public sequence datbases, the NOV20a protein was found to have homology to the proteins shown in the BLASTP data in Table 20D.

TABLE 20D
Public BLASTP Results for NOV20a
			Identities/
		NOV20a	Similarities
Protein		Residues/	for the
Accession		Match	Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
A30992	probable nicotinic acetylcholine	369 . . . 428	48/61 (78%)	2e−17
	receptor precursor - rat, 517 aa.	31 . . . 91	54/61 (87%)
AAM11659	NICOTINIC ACETYLCHOLINE	378 . . . 428	42/51 (82%)	2e−15
	RECEPTOR BETA4 SUBUNIT -	17 . . . 67	47/51 (91%)
	Mus musculus (Mouse), 495 aa.
P30926	Neuronal acetylcholine receptor	379 . . . 428	42/50 (84%)	4e−15
	protein, beta-4 chain precursor -	19 . . . 68	47/50 (94%)
	Homo sapiens (Human), 498 aa.
AAL88712	NEURONAL NICOTINIC	379 . . . 428	41/50 (82%)	1e−14
	ACETYLCHOLINE RECEPTOR	19 . . . 68	47/50 (94%)
	BETA4 SUBUNIT - Bos taurus
	(Bovine), 496 aa.
B35721	nicotinic acetylcholine receptor	379 . . . 428	41/50 (82%)	2e−14
	beta-4 chain precursor - rat, 495 aa.	18 . . . 67	46/50 (92%)

[0404] PFam analysis predicts that the NOV20a protein contains the domains shown in the Table 20E.

TABLE 20E
Domain Analysis of NOV20a
		Identities/
		Similarities
Pfam	NOV20a	for the	Expect
Domain	Match Region	Matched Region	Value
Neur_chan_LBD	387 . . . 428	14/47 (30%)	0.0064
		33/47 (70%)

Example 21

[0405] The NOV21 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 21A.

TABLE 21A
NOV21 Sequence Analysis
                 SEQ ID NO:41          2879 bp
NOV21a,          TTCGTCCCGGGCGGTGCGTTCCACTGCTCTGGGGCCGGCGCCGCGCCCAGTCCCGCTT
CG106002-01      CGGGCCGCAAGCCCCACCGCTCCCCTCCCCGGGCAGGGGCGCCGCGCAGCCCGCTCCC
DNA Sequence     GCCGCCACCTCCTCCCCTGCCGCCCTCCTAGCCGGCAGGAATTGCGCGACCACAGCGC
                 CGCTCGCGTCGCCCGCATCAGCTCAGCCCGCTGCCGCTCGGCCCTCGGCACCGCTCCG
                 GGTCCGGCCGCCGCGCGGCCAGGGCTCCCCCTGCCCAGCGCTCCCAGGCCCCGCCACG
                 CGTCGCCGCGCCCAGCTCCAGTCTCCCCTCCCCGGGGTCTCGCCAGCCCCTTCCTGCA
                 GCCGCCGCCTCCGAAGGAGCGGGTCCGCCGCGGGTAACCATGCCTAGCAAAACCAAGT
                 ACAACCTTGTGGACGATGGGCACGACCTGCGGATCCCCTTGCACAACGAGGACGCCTT
                 CCAGCACGGCATCTGCTTTGAGGCCAAGTACGTAGGAAGCCTGGACGTGCCAAGGCCC
                 AACAGCAGGGTGGAGATCGTGGCTGCCATGCGCCGGATACGGTATGAGTTTAAAGCCA
                 AGAACATCAAGAAGAAGAAAGTGAGCATTATGGTTTCAGTGGATGGAGTGAAAGTGAT
                 TCTGAAGAAGAAGAAAAAGCTTCTTTTATTGCAGAAAAAGGAATGGACGTGGGATGAG
                 AGCAAGATGCTGGTGATGCAGGACCCCATCTACAGGATCTTCTATGTCTCTCATGATT
                 CCCAAGACTTGAAGATCTTCAGCTATATCGCTCGAGATGGTGCCAGCAATATCTTCAG
                 GTGTAACGTCTTTAAATCCAAGAAGAAGAGCCAAGCTATGAGAATCGTTCGGACGGTG
                 GGGCAGGCCTTTGAGGTCTGCCACAAGCTGAGCCTGCAGCACACGCAGCAGAATGCAG
                 ATGGCCAGGAAGATGGAGAGAGTGAGAGGAACAGCAACAGCTCAGGAGACCCAGGCCG
                 CCAGCTCACTGGAGCCGAGAGGGCCTCCACGGCCACTGCAGAGGAGACTGACATCGAT
                 GCGGTGGAGGTCCCACTTCCAGGGAATGATGTCCTGGAATTCAGCCGAGGTGTGACTG
                 ATCTAGATGCTGTAGGGAAGGAAGGAGGCTCTCACACAGGCTCCAAGGTTTCGCACCC
                 CCAGGAGCCCATGCTGACAGCCTCACCCAGGATGCTGCTCCCTTCTTCTTCCTCGAAG
                 CCTCCAGGCCTGGGCACAGAGACACCGCTGTCCACTCACCACCAGATGCAGCTCCTCC
                 AGCAGCTCCTCCAGCAGCAGCAGCAGCAGACACAAGTGGCTGTGGCCCAGGTACACTT
                 GCTGAAGGACCAGTTGGCTGCTGAGGCTGCGGCGCGGCTGGAGGCCCAGGCTCGCGTG
                 CATCAGCTTTTGCTGCAGAACAAGGACATGCTCCAGCACATCTCCCTGCTGGTCAAGC
                 AGGTGCAAGAGCTGGAACTGAAGCTGTCAGGACAGAACGCCATGGGCTCCCAGGACAG
                 CTTGCTGGAGATCACCTTCCGCTCCGGAGCCCTGCCCGTGCTCTGTGACCCCACGACC
                 CCTAAGCCAGAGGACCTGCATTCGCCGCCGCTGGGCGCGGGCTTGGCTGACTTTGCCC
                 ACCCTGCGGGCAGCCCCTTAGGTAGGCGCGACTGCTTGGTGAAGCTGGAGTGCTTTCG
                 CTTTCTTCCGCCCGAGGACACCCCGCCCCCAGCGCAGGGCGAGGCGCTCCTGGGCGGT
                 CTGGAGCTCATCAAGTTCCGAGAGTCAGGCATCGCCTCGGAGTACGAGTCCAACACGG
                 ACGAGAGCGAGGAGCGCGACTCGTGGTCCCAGGAGGAGCTGCCGCGCCTGCTGAATGT
                 CCTGCAGAGGCAGGAACTGGGCGACGGCCTGGATGATGAGATCGCCGTGTAGGTGCCG
                 AGGGCGAGGAGATGGAGGCGGCGGCGTGGCTGGAGGGGCCGTGTCTGGCTGCTGCCCG
                 GGTAGGGGATGCCCAGTGAATGTGCACTGCCGAGGAGAATGCCAGCCAGGGCCCGGGA
                 GAGTGTGAGGTTTCAGGAAAGTATTGAGATTCTGCTTTGGAGGGTAAAGTGGGGAAGA
                 AATCGGATTCCCAGAGGTGAATCAGCTCCTCTCCTACTTGTGACTAGAGGGTGGTGGA
                 GGTAAGGCCTTCCAGAGCCCATGGCTTCAGGAGAGGGTCTCTCTCCAGGACTGCCAGG
                 CTGCTGGAGGACCTGCCCCTACCTGCTGCATCGTCAGGCTCCCACGCTTTGTCCGTGA
                 TGCCCCCCTACCCCCTCACTCTCCCCGTCTCCATGGTCCCGACCAGGAAGGGAAGCCA
                 TCGGTACCTTCTCAGGTACTTTGTTTCTGGATATCACGATGCTGCGAGTTGCCTAACC
                 CTCCCCCTACCTTTATGAGAGGAATTCCTTCTCCAGGCCCTTGCTGAGATTGTAGAGA
                 TTGAGTGCTCTGGACCGCAAAAGCCAGGCTAGTCCTTGTAGGGTGAGCATGGAATTGG
                 AATGTGTCACAGTGGATAAGCTTTTAGAGGAACTGAATCCAAACATTTTCTCCAGCCG
                 GACATTGAATGTTGCTACAAAGGGAGCCTTGAAGCTTTAACATGGTTCAGGCCCTTGG
                 TGTGAGAGCCCAGGGGGAGGACAGCTTGTCTGCTGCTCCAAATCACTTAGATCTGATT
                 CCTGTTTTGAAAGTCCTGCCCTGCCTTCCTCCTGCCTGTAGCCCAGCCCATCTAAATG
                 GAAGCTGGGAATTGCCCCTCACCTCCCCTGTGTCCTGTCCAGCTGAAGCTTTTGCAGC
                 ACTTTACCTCTCTGAAAGCCCCAGAGGACCAGAGCCCCCAGCCTTACCTCTCAACCTG
                 TCCCCTCCACTGGGCAGTGGTGGTCAGTTTTTACTGC
                 ORF Start: ATG at 388 ORF Stop: TAG at 1906
                 SEQ ID NO:42          506 aa MW at 56149.2 kD
NOV21a,          MPSKTKYNLVDDGHDLRIPLHNEDAFQHGICFEAKYVGSLDVPRPNSRVEIVAAMRRI
CG106002-01      RYEFKAKNIKKKKVSIMVSVDGVKVILKKKKKLLLLQKKEWTWDESKMLVMQDPIYRI
Protein Sequence FYVSHDSQDLKIFSYIARDGASNIFRCNVFKSKKKSQAMRIVRTVGQAFEVCHKLSLQ
                 HTQQNADGQEDGESERNSNSSGDPGRQLTGAERASTATAEETDIDAVEVPLPGNDVLE
                 FSRGVTDLDAVGKEGGSHTGSKVSHPQEPMLTASPRMLLPSSSSKPPGLGTETPLSTH
                 HQMQLLQQLLQQQQQQTQVAVAQVHLLKDQLAAEAAARLEAQARVHQLLLQNKDMLQH
                 ISLLVKQVQELELKLSGQNAMGSQDSLLEITFRSGALPVLCDPTTPKPEDLHSPPLGA
                 GLADFAHPAGSPLGRRDCLVKLECFRFLPPEDTPPPAQGEALLGGLELIKFRESGIAS
                 EYESNTDESEERDSWSQEELPRLLNVLQRQELGDGLDDEIAV

[0406] Further analysis of the NOV21a protein yielded the following properties shown in Table 21B.

TABLE 21B
Protein Sequence Properties NOV21a
PSort     0.9700 probability located in nucleus;
analysis: 0.3000 probability located in microbody (peroxisome);
          0.1000 probability located in mitochondrial matrix space;
          0.1000 probability located in lysosome (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0407] 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.

TABLE 21C
Geneseq Results for NOV21a
		NOV21a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
ABB04838	LDL receptor binding protein	1 . . . 506	476/508 (93%)	0.0
	CAPON SEQ ID NO: 61 -	1 . . . 503	483/508 (94%)
	Synthetic, 503 aa. [WO200184159-
	A2, 08-NOV-2001]
AAY28473	Rat Capon protein - Rattus sp, 503	1 . . . 506	476/508 (93%)	0.0
	aa. [WO9937768-A1, 29-JUL-1999]	1 . . . 503	483/508 (94%)
ABB04846	LDL receptor binding protein	1 . . . 506	432/508 (85%)	0.0
	CAPON SEQ ID NO: 69 -	1 . . . 503	444/508 (87%)
	Synthetic, 503 aa. [WO200184159-
	A2, 08-NOV-2001]
ABB04847	LDL receptor binding protein	1 . . . 506	429/508 (84%)	0.0
	CAPON SEQ ID NO: 70 -	1 . . . 503	440/508 (86%)
	Synthetic, 503 aa. [WO200184159-
	A2, 08-NOV-2001]
ABB04845	LDL receptor binding protein	1 . . . 506	431/508 (84%)	0.0
	CAPON SEQ ID NO: 68 -	1 . . . 503	440/508 (85%)
	Synthetic, 503 aa. [WO200184159-
	A2, 08-NOV-2001]

[0408] In a BLAST search of public sequence datbases, the NOV21a protein was found to have homology to the proteins shown in the BLASTP data in Table 21D.

TABLE 21D
Public BLASTP Results for NOV21a
		NOV21a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
O75052	KIAA0464 PROTEIN - Homo	1 . . . 506	506/506 (100%)	0.0
	sapiens (Human), 586 aa	81 . . . 586	506/506 (100%)
	(fragment).
O54960	CARBOXYL-TERMINAL PDZ	1 . . . 506	476/508 (93%)	0.0
	LIGAND OF NEURONAL	1 . . . 503	483/508 (94%)
	NITRIC OXIDE SYNTHASE -
	Rattus norvegicus (Rat), 503 aa.
Q9D3A8	6330408P19RIK PROTEIN - Mus	1 . . . 316	295/317 (93%)	e−165
	musculus (Mouse), 325 aa.	1 . . . 312	300/317 (94%)
O43564	CARBOXYL-TERMINAL PDZ	354 . . . 506	153/153 (100%)	2e−84
	LIGAND OF NEURONAL	1 . . . 153	153/153 (100%)
	NITRIC OXIDE SYNTHASE -
	Homo sapiens (Human), 153 aa
	(fragment).
AAL68331	RE71517P - Drosophila	1 . . . 382	166/384 (43%)	1e−72
	melanogaster (Fruit fly), 698 aa.	1 . . . 358	230/384 (59%)

[0409] PFam analysis predicts that the NOV21a protein contains the domains shown in the Table 21E.

TABLE 21E
Domain Analysis of NOV21a
		Identities/
Pfam		Similarities	Expect
Domain	NOV21a Match Region	for the Matched Region	Value
PID	32 . . . 175	49/167 (29%)	6.2e−44
		127/167 (76%)

Example 22

[0410] The NOV22 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 22A.

TABLE 22A
NOV22 Sequence Analysis
                 SEQ ID NO:43          3252 bp
NOV22a,          GGCTGCCTGACCTCCTTGGGTGCTTGCTATTAATTAACAGACTTTGTGGGGAAAAAAA
CG106868-01      GGAGCTTGCCTTCTGAGCTTTGTACCAAAGACCTGGGAAAAATTTCAAATTATAACCT
DNA Sequence     ATTTCCTGCACCATTGCTGACGCCTGGTGATCCATGTCAGAAGTACTTCCAGCTGACT
                 CAGGTGTTGACACCTTGGCAGTGTTTATGGCCAGCAGCGGAACTACAGACGTCACAAA
                 TCGGAACAGCCCAGCCACACCACCAAACACCCTTAACCTCCGATCCTCCCACAATGAA
                 CTGTTGAACGCTGAAATAAAACACACAGAAACCAAGAACAGCACACCTCCCAAATGCA
                 GGAAAAAATATGCACTAACTAACATCCAGGCGGCCATGGGCCTCTCGGATCCAGCTGC
                 ACAGCCCCTGCTGGGAAATGGCTCTGCCAACATCAAGCTGGTGAAAAATGGGGAGAAC
                 CAGCTCCGTAAGGCTGCAGAGCAAGGGCAGCAGGACCCCAACAAAAACCTGAGCCCCA
                 CTGCAGTCATCAACATAACTTCTGAGAAGTTAGAGGGTAAAGAGCCCCACCCACAGGA
                 TTCCTCGAGCTGTGAGATTTTACCCTCCCAGCCCAGGAGAACTAAGAGCTTCCTAAAT
                 TACTATGCAGATCTGGAAACCTCAGCCAGAGAACTAGAGCAGAACCGAGGCAATCACC
                 ATGGGACTGCGGAAGAGAAATCCCAGCCAGTCCAGGGCCAGGCCTCCACCATCATTGG
                 GAATGGCGATTTGCTGCTGCAGAAACCAAACAGACCCCAGTCCAGCCCTGAAGACGGC
                 CAAGTAGCCACAGTGTCATCCAGCCCAGAAACCAAGAAGGATCATCCGAAAACAGGGG
                 CCAAAACCGACTGTGCACTGCACCGGATCCAGAACCTGGCACCGAGCGATGAGGAGTC
                 CAGCTGGACAACGTTGTCCCAAGACAGTGCCTCACCCAGCTCCCCGGATGAAACAGCA
                 GATATATGGAGTGATCACTCATTTCAGACTGATCCAGATTTGCCGCCTGGCTGGAAAA
                 GAGTCAGTGACATTGCCGGGACCTATTATTGGCACATCCCAACAGGAACGACTCAGTG
                 TCTGTAACGCCATCTCCCACCCCAGAGAACGAGAAACAGCCATGGAGTGATTTTGCTG
                 TTCTGAATGGGGGAAAGATTAATAGTGACATTTGGAAGGATTTGCATGCAGCCACTGT
                 TAACCCGGACCCCAGTTTAAAAGAGTTTGAAGGAGCAACCCTACGCTATGCATCTTTG
                 AAACTCAGAAATGCCCCACACCCTGATGATGATGATTCTTGTAGTATCAACAGTGACC
                 CAGAAGCCAAGTGTTTTGCTGTGCGTTCTCTGGGATGGGTAGAGATGGCAGAAGAGGA
                 CCTCGCCCCCGGTAAAAGTAGTGTTGCGGTCAACAACTGCATCAGGCAACTTTCCTAC
                 TGCAAAAATGACATCCGAGACACAGTCGGGATTTGGGGAGAGGGGAAAGACATGTACC
                 TGATCCTGGAGAATGACATGCTCAGCCTGGTGGACCCCATGGACCGCAGCGTGCTGCA
                 CTCGCAGCCCATCGTCAGCATCCGCGTGTGGGGCGTGGGCCGCGACAATGGCCGGGAT
                 TTTGCTTATGTAGCAAGAGATAAAGATACAAGAATTTTGAAATGTCATGTATTTCGAT
                 GTGACACACCAGCAAAAGCCATTGCCACAAGTCTCCACGAGATCTGCTCCAAGATTAT
                 GGCTGAACGGAAGAATGCCAAAGCGCTGGCCTGCAGCTCCTTACAGGAAAGGGCCAAT
                 GTGAACCTCGATGTCCCTTTGCAAGTAGATTTTCCAACACCAAAGACTGAGCTGGTCC
                 AGAAGTTCCACGTGCAGTACTTGGGCATGTTACCTGTAGACAAACCAGTCGGAATGGA
                 TATTTTGAACAGTGCCATAGAAAATCTTATGACCTCATCCAACAAGGAGGACTGGCTG
                 TCAGTGAACATGAACGTGGCTGATGCCACTGTGACTGTCATCAGTGAAAAGAATGAAG
                 AGGAAGTCTTAGTGGAATGTCGTGTGCGATTCCTGTCCTTCATGGGTGTTGGGAAGGA
                 CGTCCACACATTTGCCTTCATCATGGACACGGGGAACCAGCGCTTTGAGTGCCACGTT
                 TTCTGGTGCGAGCCTAATGCTGGTAACGTGTCTGAAGCGGTGCAGGCCGCCTGCATGT
                 TACGATATCAGAAGTGCTTGGTAGCCAGGCCGCCTTCTCAGAAAGTTCGACCACCTCC
                 ACCGCCAGCAGATTCAGCGACCAGAAGAGTCACGACCAATGTAAAACGAGGGGTCTTA
                 TCCCTCATTGACACTTTGAAACAGAAACGCCCTGTCACCGAAATGCCATAGCTGCACA
                 TGCAAAAGGACTCGGCTATTTACCTGAAGATTGACTAGCTACACTAAAGAAAATGAAC
                 TCCGCCATCCGACCTTCCATCCAGTTGCTGATGCTTTGTCTTCAGAGAATTTACCCTT
                 AACCAAGCAGTGTTAGACAAGCATGTTCTCTCGTCTTGCCACCATCATGTGATATGAA
                 AAGAAGCATGAATAATTTTTTTTGCTGTAAGTTACATCATGCGCAGTGGAAGGTCTTT
                 TTCTTATTGTAAATATTGTGAACATTACTTAACTTCACACACACACAGAGAAGAGTGT
                 GGCCCCACCCCTCCTAGTGAACTAACGCTGCGTCCTTGGAATGAATGATGCGTGAGTT
                 AGTTTCACTGTCTTCTTGGCTGGACCTGTCACAAGCAACCTTTAAGTCCTACAGCACT
                 TTGCCCTGTTTTCAACATTGGAGTAGGCACTGCATAGCAGATACCATTGAATTGCTGT
                 AAAAATAGGATGGCGAGTTTGTGTTTTAATTTTTCATAAAATTGAACCTGTTGGTTGA
                 CAAAATTGGCTGTTGGCATCAGTATAGAAACCAACTGGCAGCTTTCCCTGACAAGCTC
                 TTTGACACATGGACACCATTTCATGTCTACAGCTGTTTGTGGGATGTTGGAAAAAAAT
                 GAAACTTCAAAATTGATGAAAAACTAAATTCGAGGAATTAAAATCGAACAAAACATAG
                 CCTTTCTTTTCCGATGGTTTTCAAACTGATTATTTTTAAAAGAGATTAATAAAATCAT
                 AATGCATTTTGGGTGGGACATATTTCAAGCTTCTGCCTTATATTGTACCTGCCCGGGC
                 GGAA
                 ORF Start: ATG at 150 ORF Stop: TAG at 2427
                 SEQ ID NO:44          759 aa MW at 83415.8 kD
NOV22a,          MSEVLPADSGVDTLAVFMASSGTTDVTNRNSPATPPNTLNLRSSHNELLNAEIKHTET
CG106868-01      KNSTPPKCRKKYALTNIQAAMGLSDPAAQPLLGNGSANIKLVKNGENQLRKAAEQGQQ
Protein Sequence DPNKNLSPTAVINITSEKLEGKEPHPQDSSSCEILPSQPRRTKSFLNYYADLETSARE
                 LEQNRGNHHGTAEEKSQPVQGQASTIIGNGDLLLQKPNRPQSSPEDGQVATVSSSPET
                 KKDHPKTGAKTDCALHRIQNLAPSDEESSWTTLSQDSASPSSPDETADIWSDHSFQTD
                 PDLPPGWKRVSDIAGTYYWHIPTGTTQWERPVSIPADLQGSRKGSLSSVTPSPTPENE
                 KQPWSDFAVLNGGKINSDIWKDLHAATVNPDPSLKEFEGATLRYASLKLRNAPHPDDD
                 DSCSINSDPEAKCFAVRSLGWVEMAEEDLAPGKSSVAVNNCIRQLSYCKNDIRDTVGI
                 WGEGKDMYLILENDMLSLVDPMDRSVLHSQPIVSIRVWGVGRDNGRDFAYVARDKDTR
                 ILKCHVFRCDTPAKAIATSLHEICSKIMAERKNAKALACSSLQERANVNLDVPLQVDF
                 PTPKTELVQKFHVQYLGMLPVDKPVGMDILNSAIENLMTSSNKEDWLSVNMNVADATV
                 TVISEKNEEEVLVECRVRFLSFMGVGKDVHTFAFIMDTGNQRFECHVFWCEPNAGNVS
                 EAVQAACMLRYQKCLVARPPSQKVRPPPPPADSATRRVTTNVKRGVLSLIDTLKQKRP
                 VTEMP

[0411] Further analysis of the NOV22a protein yielded the following properties shown in Table 22B.

TABLE 22B
Protein Sequence Properties NOV22a
PSort     0.3000 probability located in nucleus;
analysis: 0.1000 probability located in mitochondrial matrix space;
          0.1000 probability located in lysosome (lumen);
          0.0000 probability located in endoplasmic reticulum
          (membrane)
SignalP   No Known Signal Sequence Predicted
analysis:

[0412] 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.

TABLE 22C
Geneseq Results for NOV22a
		NOV22a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAY13459	Amino acid sequence of human	44 . . . 759	695/716 (97%)	0.0
	Fe65-like protein - Homo sapiens,	16 . . . 730	699/716 (97%)
	730 aa. [WO9921995-A1, 06-MAY-1999]
AAY13458	Amino acid sequence of human	20 . . . 753	345/752 (45%)	e−168
	Fe65 - Homo sapiens, 710 aa.	5 . . . 704	465/752 (60%)
	[WO9921995-A1, 06-MAY-1999]
AAY13454	Amino acid sequence of rat Fe65 -	250 . . . 759	282/515 (54%)	e−156
	Rattus sp, 499 aa. [WO9921995-	1 . . . 499	367/515 (70%)
	A1, 06-MAY-1999]
AAW24798	Carboxy-terminal region of	250 . . . 759	282/515 (54%)	e−156
	amyloid precursor protein - Homo	1 . . . 499	367/515 (70%)
	sapiens, 499 aa. [FR2740454-A1,
	30-APR-1997]
AAW49835	Amino acid sequence of the rat	346 . . . 753	233/412 (56%)	e−126
	protein FE65 - Rattus sp, 425 aa.	2 . . . 410	299/412 (72%)
	[WO9821327-A1, 22-MAY-1998]

[0413] In a BLAST search of public sequence datbases, the NOV22a protein was found to have homology to the proteins shown in the BLASTP data in Table 22D.

TABLE 22D
Public BLASTP Results for NOV22a
		NOV22a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q92870	Amyloid beta A4 precursor protein-	44 . . . 759	695/716 (97%)	0.0
	binding family B member 2 (Fe65-	16 . . . 730	699/716 (97%)
	like protein) - Homo sapiens
	(Human), 730 aa (fragment).
Q9QXJ1	Amyloid beta A4 precursor protein-	20 . . . 759	350/757 (46%)	e−172
	binding family B member 1 (Fe65	5 . . . 708	474/757 (62%)
	protein) - Mus musculus (Mouse),
	708 aa.
Q99MK3	FE65 - Rattus norvegicus (Rat), 711	20 . . . 759	347/759 (45%)	e−170
	aa.	5 . . . 711	467/759 (60%)
Q96A93	SIMILAR TO AMYLOID BETA	20 . . . 753	345/750 (46%)	e−169
	(A4) PRECURSOR PROTEIN-	5 . . . 702	465/750 (62%)
	BINDING, FAMILY B, MEMBER
	1 (FE65) - Homo sapiens (Human),
	708 aa.
O00213	Amyloid beta A4 precursor protein-	20 . . . 753	345/752 (45%)	e−168
	binding family B member 1 (Fe65	5 . . . 704	465/752 (60%)
	protein) - Homo sapiens (Human),
	710 aa.

[0414] PFam analysis predicts that the NOV22a protein contains the domains shown in the Table 22E.

TABLE 22E
Domain Analysis of NOV22a
		Identities/
Pfam		Similarities	Expect
Domain	NOV22a Match Region	for the Matched Region	Value
WW	293 . . . 321	15/30 (50%)	3e−09
		24/30 (80%)
PID	420 . . . 556	47/161 (29%)	1.1e−50
		128/161 (80%)
PID	591 . . . 713	46/161 (29%)	1.8e−46
		112/161 (70%)

Example 23

[0415] The NOV23 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 23A.

TABLE 23A
NOV23 Sequence Analysis
                 SEQ ID NO:45         1322 bp
NOV23a,          CGCGCCTGAAGAGCCGCAGAGAGAGCTGGGAGCTAAGGGGTGGCGGCGACCGGAAGCG
CG106988-01      CAGTGCACACCCCCATGGCCCGGGCTTTGGTCCAGCTCTGGGCCATATGCATGCTGCG
DNA Sequence     AGTGGCGCTGGCTACCGTCTATTTCCAAGAGGAATTTCTAGACGGAGAGCATTGGAGA
                 AACCGATGGTTGCAGTCCACCAATGACTCCCGATTTGGGCATTTTAGACTTTCGTCGG
                 GCAAGTTTTATGGTCATAAAGAGAAAGATAAAGGTCTGCAAACCACTCAGAATGGCCG
                 ATTCTATGCCATCTCTGCACGCTTCAAACCGTTCAGCAATAAAGGGAAAACTCTGGTT
                 ATTCAGTACACAGTAAAACATGAGCAGAAGATGGACTGTGGAGGGGGCTACATTAAGG
                 TCTTTCCTGCAGACATTGACCAGAAGAACCTGAATGGAAAATCGCAGTACTATATTAT
                 GTTTGGACCCGATATTTGTGGATTTGATATCAAGAAAGTTCATGTTATTTTACATTTC
                 AAGAATAAGTATCACGAAAACAAGAAACTGATCAGGTGTAAGGTTGATGGCTTCACAC
                 ACCTGTACACTCTAATTTTAAGACCAGATCTTTCTTATGATGTGAAAATTGATGGTCA
                 GTCAATTGAATCCGGCAGCATAGAGTACGACTGGAACTTAACATCACTCAAGAAGGAA
                 ACGTCCCCGGCAGAATCGAAGGATTGGGAACAGACTAAAGACAACAAAGCCCAGGACT
                 GGGAGAAGCATTTTCTGGACGCCAGCACCAGCAAGCAGAGCGACTGGAACGGTGACCT
                 GGATGGGGACTGGCCAGCGCCGATGCTCCAGAAGCCCCCGTACCAGGATGGCCTGAAA
                 CCAGAAGGTATTCATAAAGACGTCTGGCTCCACCGTAAGATGAAGAATACCGACTATT
                 TGACGCAGTATGACCTCTCAGAATTTGAGAACATTGGTGCCATTGGCCTGGAGCTTTG
                 GCAGGTCATTTGGCATCTGCAGGTGAGATCTGGAACCATTTTTGATAACTTTCTGATC
                 ACAGATGATGAAGAGTACGCAGATAATTTTGGCAAGGCCACCTGGGGCGAAACCAAGG
                 GTCCAGAAAGGGAGATGGATGCCATACAGGCCAAGGAGGAAATGAAGAAGGCCCGCGA
                 GGAAGAGGAGGAAGAGCTGCTGTCGGGAAAAATTAACAGGCACGAACATTACTTCAAT
                 CAATTTCACAGAAGGAATGAACTTTAGTGATCCCCATTGGATATAAGGATGACTGGTA
                 AAATCTCATTGCTACTTTAATCTATGTTTCAAACTCAAATGTCAAA
                 ORF Start: ATG at 73 ORF Stop: TAG at 1243
                 SEQ ID NO:46         390 aa MW at 45772.2 kD
NOV23a,          MARALVQLWAICMLRVALATVYFQEEFLDGEHWRNRWLQSTNDSRFGHFRLSSGKFYG
CG106988-01      HKEKDKGLQTTQNGRFYAISARFKPFSNKGKTLVIQYTVKHEQKMDCGGGYIKVFPAD
Protein Sequence IDQKNLNGKSQYYIMFGPDICGFDIKKVHVILHFKNKYHENKKLIRCKVDGFTHLYTL
                 ILRPDLSYDVKIDGQSIESGSIEYDWNLTSLKKETSPAESKDWEQTKDNKAQDWEKHF
                 LDASTSKQSDWNGDLDGDWPAPMLQKPPYQDGLKPEGIHKDVWLHRKMKNTDYLTQYD
                 LSEFENIGAIGLELWQVIWHLQVRSGTIFDNFLITDDEEYADNFGKATWGETKGPERE
                 MDAIQAKEEMKKAREEEEEELLSGKINRHEHYFNQFHRRNEL

[0416] Further analysis of the NOV23a protein yielded the following properties shown in Table 23B.

TABLE 23B
Protein Sequence Properties NOV23a
PSort     0.6377 probability located in outside;
analysis: 0.2484 probability located in microbody (peroxisome);
          0.1900 probability located in lysosome (lumen);
          0.1000 probability located in endoplasmic
          reticulum (membrane)
SignalP   Cleavage site between residues 20 and 21
analysis:

[0417] 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.

TABLE 23C
Geneseq Results for NOV23a
		NOV23a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAB32385	Human secreted protein sequence	1 . . . 390	384/390 (98%)	0.0
	encoded by gene 15 SEQ ID NO: 71 -	1 . . . 384	384/390 (98%)
	Homo sapiens, 385 aa.
	[WO200047602-A1, 17-AUG-2000]
AAY92349	Human MBP-calreticulin - Homo	14 . . . 368	192/376 (51%)	e−108
	sapiens, 417 aa. [WO200020577-	14 . . . 383	254/376 (67%)
	A1, 13-APR-2000]
AAP92276	60 kD Ro (Ro/SSA) antigen -	14 . . . 368	192/376 (51%)	e−108
	Synthetic, 417 aa. [WO8909273-A,	14 . . . 383	254/376 (67%)
	05-OCT-1989]
AAY00927	Calreticulin - Homo sapiens, 417	14 . . . 368	192/376 (51%)	e−107
	aa. [WO9907406-A1, 18-FEB-1999]	14 . . . 383	253/376 (67%)
AAY92350	Recombinant human MBP-	21 . . . 368	189/369 (51%)	e−107
	calreticulin - Homo sapiens, 400 aa.	4 . . . 366	251/369 (67%)
	[WO200020577-A1, 13-APR-2000]

[0418] In a BLAST search of public sequence datbases, the NOV23a protein was found to have homology to the proteins shown in the BLASTP data in Table 23D.

TABLE 23D
Public BLASTP Results for NOV23a
		NOV23a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q96LN3	CDNA FLJ25355 FIS, CLONE	1 . . . 390	384/390 (98%)	0.0
	TST01593 - Homo sapiens	1 . . . 384	384/390 (98%)
	(Human), 384 aa.
Q96L12	SIMILAR TO RIKEN CDNA	1 . . . 390	383/390 (98%)	0.0
	1700031L01 GENE - Homo sapiens	1 . . . 384	383/390 (98%)
	(Human), 384 aa.
Q9D9Q6	1700031L01RIK PROTEIN - Mus	2 . . . 390	319/390 (81%)	0.0
	musculus (Mouse), 380 aa.	4 . . . 380	350/390 (88%)
P18418	Calreticulin precursor (CRP55)	14 . . . 378	192/386 (49%)	e−108
	(Calregulin) (HACBP) (ERP60)	14 . . . 393	260/386 (66%)
	(CALBP) (Calcium-binding protein
	3) (CABP3) - Rattus norvegicus
	(Rat), 416 aa.
P27797	Calreticulin precursor (CRP55)	14 . . . 368	192/376 (51%)	e−107
	(Calregulin) (HACBP) (ERp60) -	14 . . . 383	254/376 (67%)
	Homo sapiens (Human), 417 aa.

[0419] PFam analysis predicts that the NOV23a protein contains the domains shown in the Table 23E.

TABLE 23E
Domain Analysis of NOV23a
	NOV23a	Identities/Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
calreticulin	21 . . . 200	99/207 (48%)	9.1e−93
		148/207 (71%)
calreticulin	275 . . . 324	24/51 (47%)	4e−11
		35/51 (69%)

Example 24

[0420] The NOV24 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 24A.

TABLE 24A
NOV24 Sequence Analysis
                 SEQ ID NO:47          543 bp
NOV24a,          ATGGCTGCCCGGACGCGGAGCGAGAGGGTGAGAGAGTCCGAGACACTATCCCGTTCCC
CG107363-01      TTCCGTCGCGCAGACCCTGCCGGAGCCGCTGCCGCTATGGATGATCGAGAGGATCTGG
DNA Sequence     TGTACCAGGCGAAGCTGGCCGAGCAGGCTGAGCGATACGACGAAATGGTGGAGTCAAT
                 GAAGAAAGAAGAAAACAAGGGAGGAGAAGACAAGCTAAAAATGATTCGGGAATATCGG
                 CAAATGGTTGAGACTGAGCTAAAATTAATCTGTTGTGACATTCTGGATGTACTGGACA
                 AACACCTCATTCCAGCAGCTAACACTGGCGAGTCCAAGGTTTTCTATTATAAAATGAA
                 AGGGGACTACCACAGGTATCTGGCAGAATTTGCCACAGGAAACGACAGGAAGGAGGCT
                 GCGGAGAACAGCCTAGTGGCTTATAAAGCTGCTAGTGATATTGCAACAATCCGTGGCT
                 GCTCATTCTTGCCTACTTTACTCTCCCACTGAAGCAGGTTAGCGTTGAAGGTGGTATG
                 GAAAAGCCTGCATGCCTGTTC
                 ORF Start: ATG at 95  ORF Stop: TGA at 494
                 SEQ ID NO:48          133 aa MW at 15309.2 kD
NOV24a,          MDDREDLVYQAKLAEQAERYDEMVESMKKEENKGGEDKLKMIREYRQMVETELKLICC
CG107363-01      DILDVLDKHLIPAANTGESKVFYYKMKGDYHRYLAEFATGNDRKEAAENSLVAYKAAS
Protein Sequence DIATIRGCSFLPTLLSH
                 SEQ ID NO:49          766 bp
NOV24b,          ATGGCTGCCCGGACGCGGAGCGAGAGGGTGAAAAAAGTCGGAAACACTATCCGCTTCC
CG107363-02      ATCCGTCGCGCAGACCCTGCCGGAGCCGCTGCCGCTATGGATGATCGAGAGGATCTGG
DNA Sequence     TGTACCAGGCGAAGCTGGCCGAGCAGGCTGAGCGATACGACGAAATGGTGGAGTCAAT
                 GAAGAAAGAAGAAAACAAGGGAGGAGAAGACAAGCTAAAAATGATTCGGGAATATCGG
                 CAAATGGTTGAGACTGAGCTAAAATTAATCTGTTGTGACATTCTGGATGTACTGGACA
                 AACACCTCATTCCAGCAGCTAACACTGGCGAGTCCAAGGTTTTCTATTATAAAATGAA
                 AGGGGACTACCACAGGTATCTGGCAGAATTTGCCACAGGAAACGACAGGAAGGAGGCT
                 GCGGAGAACAGCCTAGTGGCTTATAAAGCTGCTAGTGATATTGCAATGACAGAACTTC
                 CACCAACGCATCCTATTCGCTTAGGTCTTGCTCTCAATTTTTCCGTATTCTACTACGA
                 AATTCTTAATTCCCCTGACCGTGCCTGCAGGTTGGCAAAAGCAGCTTTTGATGATGCA
                 ATTGCAGAACTGGATACGCTGAGTGAAGAAAGCTATAAGGACTCTACACTTATCATGC
                 AGTTGTTACGTGATAATCTGACACTATGGACTTCAGACATGCAGGGTGACGGTGAAGA
                 GCAGAATAAAGAAGCGCTGCAGGACGTGGAAGACGAAAATCAGTGAGACATAAGCCAA
                 CAAGAGAAACCA
                 ORF Start: ATG at 95  ORF Stop: TGA at 740
                 SEQ ID NO:50          215 aa MW at 24688.4 kD
NOV24b,          MDDREDLVYQAKLAEQAERYDEMVESMKKEENKGGEDKLKMIREYRQMVETELKLICC
CG107363-02      DILDVLDKHLIPAANTGESKVFYYKMKGDYHRYLAEFATGNDRKEAAENSLVAYKAAS
Protein Sequence DIAMTELPPTHPIRLGLALNFSVFYYEILNSPDRACRLAKAAFDDAIAELDTLSEESY
                 KDSTLIMQLLRDNLTLWTSDMQGDGEEQNKEALQDVEDENQ
                 SEQ ID NO:51          1084 bp
NOV24c,          CGGCCGCGTCGACCATTTTTGCTGCCCGGACGCGGAGCGAGAGGCTGAGAGAGTCGGA
CG107363-03      GACACTATCCGCTTCCATCCGTCGCGCAGACCCTGCCGGAGCCGCTGCCGCTATGGAT
DNA Sequence     GATCGAGAGGATCTGGTGTACCAGGCGAAGCTGGCCGAGCAGGCTGAGCGATACGACG
                 AAATGGTGGAGTCAATGAAGAAAGTAGCAGGGATGGATGTGGAGCTGACAGTTGAAGA
                 AAGAAACCTCCTATCTGTTGCATATAAGAATGTGATTGGAGCTAGAAGAGCCTCCTGG
                 AGAATAATCAGCAGCATTGAACAGAAAGAAGAAAACAAGGGAGGAGAAGACAAGCTAA
                 AAATGATTCGGGAATATCGGCAAATGGTTGAGACTGAGCTAAAGTTAATCTGTTGTGA
                 CATTCTGGATGTACTGGACAAACACCTCATTCCAGCAGCTAACACTGGCGAGTCCAAG
                 GTTTTCTATTATAAAATGAAAGGGGACTACCACAGGTATCTGGCAGAATTTGCCACAG
                 GAAACGACAGGAAGGAGGCTGCGGAGAACAGCCTAGTGGCTTATAAAGCTGCTAGTGA
                 TATTGCAATGACAGAACTTCCACCAACGCATCCTATTCGCTTAGGTCTTGCTCTCAAT
                 TTTTCCGTATTCTACTACGAAATTCTTAATTCCCCTGACCGTGCCTGCAGGTTGGCAA
                 AAGCAGCTTTTGATGATGCAATTGCAGAACTGGATACGCTGAGTGAAGAAAGCTATAA
                 GGACTCTACACTTATCATGCAGTTGTTACGTGATAATCTGACACTATGGACTTCAGAC
                 ATGCAGGGTGACGATTCCTAAAGGAAAACCCAACTCTTCCTTTCCTAAAAACTCTACT
                 TTGTGAAGAGCAGAATAAAGAAGCGCTGCAGGACGTGGAAGACGAAAATCAGTGAGAC
                 ATAAGCCAACAAGAGAAACCATCTCTGACCACCCCCTCCTCCCCATCCCACCCTTTGG
                 AAACTCCCCATTGTCACTGAGAACCACCAAATCTGACTTTTACATTTGGTCTCAGAAT
                 TTAGGTTCCTGCCCTGTTGGTTTTTTTTTTTTTTTTTAAA
                 ORF Start: ATG at 111 ORF Stop: TAA at 831
                 SEQ ID NO:52          240 aa MW at 27418.7 kD
NOV24c,          MDDREDLVYQAKLAEQAERYDEMVESMKKVAGMDVELTVEERNLLSVAYKNVIGARRA
CG107363-03      SWRIISSIEQKEENKGGEDKLKMIREYRQMVETELKLICCDILDVLDKHLIPAANTGE
Protein Sequence SKVFYYKMKGDYHRYLAEFATGNDRKEAAENSLVAYKAASDIAMTELPPTHPIRLGLA
                 LNFSVFYYEILNSPDRACRLAKAAFDDAIAELDTLSEESYKDSTLIMQLLRDNLTLWT
                 SDMQGDDS

[0421] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 24B.

TABLE 24B
Comparison of NOV24a against NOV24b and NOV24c.
		NOV24a	Identities/
	Protein	Residues/	Similarities for the Matched
	Sequence	Match Residues	Region
	NOV24b	1 . . . 119	119/119 (100%)
		1 . . . 119	119/119 (100%)
	NOV24c	1 . . . 119	119/159 (74%)
		1 . . . 159	119/159 (74%)

[0422] Further analysis of the NOV24a protein yielded the following properties shown in Table 24C.

TABLE 24C
Protein Sequence Properties NOV24a
PSort     0.4500 probability located in cytoplasm; 0.3000 probability
analysis: located in microbody (peroxisome); 0.1000
          probability located in mitochondrial matrix
          space; 0.1000 probability located in
          lysosome (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0423] 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.

TABLE 24D
Geneseq Results for NOV24a
		NOV24a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
ABG00586	Novel human diagnostic protein	1 . . . 119	119/159 (74%)	7e−58
	#577 - Homo sapiens, 255 aa.	1 . . . 159	119/159 (74%)
	[WO200175067-A2, 11-OCT-2001]
ABG00586	Novel human diagnostic protein	1 . . . 119	119/159 (74%)	7e−58
	#577 - Homo sapiens, 255 aa.	1 . . . 159	119/159 (74%)
	[WO200175067-A2, 11-OCT-2001]
AAY92333	Human 14-3-3-epsilon - Homo	1 . . . 119	119/159 (74%)	7e−58
	sapiens, 255 aa. [WO200020448-	1 . . . 159	119/159 (74%)
	A2, 13-APR-2000]
AAY13596	Cruciform binding protein (CBP) -	1 . . . 119	119/159 (74%)	7e−58
	Ovis ammon aries, 255 aa.	1 . . . 159	119/159 (74%)
	[WO9928340-A2, 10-JUN-1999]
AAB56772	Human prostate cancer antigen	1 . . . 119	118/159 (74%)	3e−57
	protein sequence SEQ ID NO: 1350 -	42 . . . 200	118/159 (74%)
	Homo sapiens, 296 aa.
	[WO200055174-A1, 21-SEP-2000]

[0424] In a BLAST search of public sequence datbases, the NOV24a protein was found to have homology to the proteins shown in the BLASTP data in Table 24E.

TABLE 24E
Public BLASTP Results for NOV24a
		NOV24a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
P42655	14-3-3 protein epsilon	1 . . . 119	119/159 (74%)	2e−57
	(Mitochondrial import stimulation	1 . . . 159	119/159 (74%)
	factor L subunit) (Protein kinase C
	inhibitor protein-1) (KCIP-1) (14-3-
	3E) - Homo sapiens (Human), 255
	aa.
S23303	protein kinase C inhibitor KCIP-1	1 . . . 112	112/152 (73%)	7e−54
	isoform epsilon - sheep, 212 aa.	1 . . . 152	112/152 (73%)
O57468	14-3-3 PROTEIN EPSILON -	1 . . . 119	111/159 (69%)	3e−52
	Xenopus laevis (African clawed	1 . . . 159	116/159 (72%)
	frog), 255 aa.
P92177	14-3-3 protein epsilon (Suppressor of	1 . . . 119	94/159 (59%)	6e−43
	RAS1 3-9) - Drosophila	1 . . . 159	108/159 (67%)
	melanogaster (Fruit fly), 260 aa.
Q9UR29	14-3-3 - Lentinula edodes (Shiitake	2 . . . 119	86/158 (54%)	1e−37
	mushroom) (Lentinus edodes), 256	3 . . . 160	102/158 (64%)
	aa.

[0425] PFam analysis predicts that the NOV24a protein contains the domains shown in the Table 24F.

TABLE 24F
Domain Analysis of NOV24a
	NOV24a	Identities/Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
14-3-3	4 . . . 28	21/25 (84%)	1.9e−09
		25/25 (100%)
14-3-3	29 . . . 120	64/92 (70%)	6.1e−40
		88/92 (96%)

Example 25

[0426] The NOV25 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 25A.

TABLE 25A
NOV25 Sequence Analysis
                 SEQ ID NO:53         3439 bp
NOV25a,          CGGGGGCGGGGGGTGGGCGGGGCCGGGCGCCGCCGCGGAGCCTCCCGGGCCGCCGCGA
CG108360-01      TCATGTCGGACCAGGCGCCCAAAGTTCCTGAGGAGATGTTCAGGGAGGTCAAGTATTA
DNA Sequence     CGCGGTGGGCGACATCGACCCGCAGGTTATTCAGCTTCTCAAGGCTGGAAAAGCGAAG
                 GAAGTTTCCTACAATGCACTAGCCTCACACATAATCTCAGAGGATGGGGACAATCCAG
                 AGGTGGGAGAAGCTCGGGAAGTCTTTGACTTACCTGTTGTAAAGCCTTCTTGGGTGAT
                 TCTGTCCGTTCAGTGTGGAACTCTTCTGCCAGTAAATGGTTTTTCTCCAGAATCATGT
                 CAGATTTTTTTTGGAATCACTGCCTGCCTTTCTCAGGTGTCATCTGAAGACAGAAGTG
                 CCCTGTGGGCTTTGGTTACGTTCTATGGGGGAGATTGCCAGCTAACCCTCAATAAGAA
                 ATGCACGCATTTGATTGTTCCAGAGCCAAAGGGGGAGAAATACGAATGTGCTTTAAAG
                 CGAGCAAGTATTAAAATTGTGACTCCTGACTGGGTTCTGGATTGCGTATCAGAGAAAA
                 CCAAAAAGGACGAAGCATTTTATCATCCTCGTCTGATTATTTATGAAGAGGAAGAAGA
                 GGAAGAGGAAGAGGAGGAGGAAGTAGAAAATGAGGAACAAGATTCTCAGAATGAGGGT
                 AGTACAGATGAGAAGTCAAGCCCTGCCAGCTCTCAAGAAGGGTCTCCTTCAGGTGACC
                 AGCAGTTTTCACCTAAATCCAACACTGAAAAATCTAAAGGGGAATTAATGTTTGATGA
                 TTCTTCAGATTCATCACCGGAAAAACAGGAGAGAAATTTAAACTGGACCCCGGCCGAA
                 GTCCCACAGTTAGCTGCAGCAAAACGCAGGCTGCCTCAGGGAAAGGAGCCTGGGTTGA
                 TTAACTTGTGTGCCAATGTCCCACCCGTCCCAGGTAACATTTTGCCCCCTGAGGTCCG
                 GGGTAATTTAATGGCTGCTGGACAAAACCTCCAAAGTTCTGAAAGATCAGAAATGATA
                 GCTACCTGGAGTCCAGCTGTACGGACACTGAGGAATATTACTAATAATGCTGACATTC
                 AGCAGATGAACCGGCCATCAAATGTAGCACATATCTTACAGACTCTTTCAGCACCTAC
                 GAAAAATTTAGAACAGCAGGTGAATCACAGCCAGCAGGGACATACAAATGCCAATGCA
                 GTGCTGTTTAGCCAAGTGAAAGTGACTCCAGAGACACACATGCTACAGCAGCAGCAGC
                 AGGCCCAGCAGCAGCAGCAGCAGCACCCGGTTTTACACCTTCAGCCCCAGCAGATAAT
                 GCAGCTCCAGCAGCAGCAGCAGCAGCAGATCTCTCAGCAACCTTACCCCCAGCAGCCG
                 CCGCATCCATTTTCACAGCAACAGCAGCAGCAGCAGCAAGCCCATCCGCATCAGTTTT
                 CACAGCAACAGCTACAGTTTCCACAGCAACAGTTGCATCCTCCACAGCAGCTGCATCG
                 CCCTCAGCAGCAGCTCCAGCCCTTTCAGCAGCAGCATGCCCTGCAGCAGCAGTTCCAT
                 CAGCTGCAGCAGCACCAGCTCCAGCAGCAGCAGCTTGCCCAGCTCCAGCAGCAGCACA
                 GCCTGCTCCAGCAGCAGCAGCAACAGCAGATTCAGCAGCAGCAGCTCCAGCGCATGCA
                 CCAGCAGCAGCAGCAGCAGCAGATGCAAAGTCAGACAGCGCCACACTTGAGTCAGACG
                 TCACAGGCGCTGCAGCATCAGGTTCCACCTCAGCAGCCCCCGCAGCAGCAGCAGCAAC
                 AGCAGCCACCACCATCGCCTCAGCAGCATCAGCTTTTTGGACATGATCCAGCAGTGGA
                 GATTCCAGAAGAAGGCTTCTTATTGGGATGTGTGTTTGCAATTGCGGATTATCCAGAG
                 CAGATGTCTGATAAGCAACTGCTGGCCACCTGGAAAAGGATAATCCAGGCACATGGCG
                 GCACTGTTGACCCCACCTTCACGAGTCGATGCACGCACCTTCTCTGTGAGAGTCAAGT
                 CAGCAGCGCGTATGCACAGGCAATAAGAGAAAGAAAGAGATGTGTTACTGCACACTGG
                 TTAAACACAGTCTTAAAGAAGAAGAAAATGGTACCGCCGCACCGAGCCCTTCACTTCC
                 CAGTGGCCTTCCCACCAGGAGGAAAGCCATGTTCACAGCATATTATTTCTGTGACTGG
                 ATTTGTTGATAGTGACAGAGATGACCTAAAATTAATGGCTTATTTGGCAGGTGCCAAA
                 TATACGGGTTATCTATGCCGCAGCAACACAGTCCTCATCTGTAAAGAACCAACTGGTT
                 TAAAGTATGAAAAAGCCAAAGAGTGGAGGATACCCTGTGTCAACGCCCAGTGGCTTGG
                 CGACATTCTTCTGGGAAACTTTGAGGCACTGAGGCAGATTCAGTATAGTCGCTACACG
                 GCATTCAGTCTGCAGGATCCATTTGCCCCTACCCAGCATTTAGTTTTAAATCTTTTAG
                 ATGCTTGGAGAGTTCCCTTAAAAGTGTCTGCAGAGTTGTTGATGAGTATAAGACTACC
                 TCCCAAACTGAAACAGAATGAAGTAGCTAATGTCCAGCCTTCTTCCAAAAGAGCCAGA
                 ATTGAAGACGTACCACCTCCCACTAAAAAGCTAACTCCAGAATTGACCCCTTTTGTGC
                 TTTTCACTGGATTCGAGCCTGTCCAGGTTCAACAGTATATTAAGAAGCTCTACATTCT
                 TGGTGGAGAGGTTGCGGAGTCTGCACAGAAGTGCACACACCTCATTGCCAGCAAAGTG
                 ACTCGCACCGTGAAGTTCCTGACGGCGATTTCTGTCGTGAAGCACATAGTGACGCCAG
                 AGTGGCTGGAAGAATGCTTCAGGTGTCAGAAGTTCATTGATGAGCAGAACTACATTCT
                 CCGAGATGCTGAGGCAGAAGTACTTTTCTCTTTCAGCTTGGAAGAATCCTTAAAACGG
                 GCACACGTTTCTCCACTCTTTAAGGCAAAATATTTTTACATCACACCTGGAATCTGCC
                 CAAGTCTTTCCACTATGAAGGCAATCGTAGAGTGTGCAGGAGGAAAGGTGTTATCCAA
                 ATTTTAATATCCTGTGAAAATGACCTTCATTTATGCCGAGAATATTTTGCCAGAGGCA
                 TAGATGTTCACAATGCAGAGTTCGTTCTGACTGGAGTGCTCACTCAAACGCTGGACTA
                 TGAATCATATAAGTTTAACTGATGGCGTCTAGGCTGCCGTGCATGTCGACTCCTGCGG
                 TGCGGGGCTGGCTGTCTGGCTGGCGAGGAGCTGCTGCGCTTCCTTCACATGCTCTTGT
                 TTTCCAGCTGCTTTCCTGGGGGATCAGACTGTGAAGCAGGAAGACAGATATAATAAAT
                 ATACTGCATCTTTTTAA
                 ORF Start: ATG at 61 ORF Stop: TGA at 3268
                 SEQ ID NO:54         1069 aa MW at 121340.7 kD
NOV25a,          MSDQAPKVPEEMFREVKYYAVGDIDPQVIQLLKAGKAKEVSYNALASHIISEDGDNPE
CG108360-01      VGEAREVFDLPVVKPSWVILSVQCGTLLPVNGFSPESCQIFFGITACLSQVSSEDRSA
Protein Sequence LWALVTFYGGDCQLTLNKKCTHLIVPEPKGEKYECALKRASIKIVTPDWVLDCVSEKT
                 KKDEAFYHPRLIIYEEEEEEEEEEEEVENEEQDSQNEGSTDEKSSPASSQEGSPSGDQ
                 QFSPKSNTEKSKGELMFDDSSDSSPEKQERNLNWTPAEVPQLAAAKRRLPQGKEPGLI
                 NLCANVPPVPGNILPPEVRGNLMAAGQNLQSSERSEMIATWSPAVRTLRNITNNADIQ
                 QMNRPSNVAHILQTLSAPTKNLEQQVNHSQQGHTNANAVLFSQVKVTPETHMLQQQQQ
                 AQQQQQQHPVLHLQPQQIMQLQQQQQQQISQQPYPQQPPHPFSQQQQQQQQAHPHQFS
                 QQQLQFPQQQLHPPQQLHRPQQQLQPFQQQHALQQQFHQLQQHQLQQQQLAQLQQQHS
                 LLQQQQQQQIQQQQLQRMHQQQQQQQMQSQTAPHLSQTSQALQHQVPPQQPPQQQQQQ
                 QPPPSPQQHQLFGHDPAVEIPEEGFLLGCVFAIADYPEQMSDKQLLATWKRIIQAHGG
                 TVDPTFTSRCTHLLCESQVSSAYAQAIRERKRCVTAHWLNTVLKKKKMVPPHRALHFP
                 VAFPPGGKPCSQHIISVTGFVDSDRDDLKLMAYLAGAKYTGYLCRSNTVLICKEPTGL
                 KYEKAKEWRIPCVNAQWLGDILLGNFEALRQIQYSRYTAFSLQDPFAPTQHLVLNLLD
                 AWRVPLKVSAELLMSIRLPPKLKQNEVANVQPSSKRARIEDVPPPTKKLTPELTPFVL
                 FTGFEPVQVQQYIKKLYILGGEVAESAQKCTHLIASKVTRTVKFLTAISVVKHIVTPE
                 WLEECFRCQKFIDEQNYILRDAEAEVLFSFSLEESLKRAHVSPLFKAKYFYITPGICP
                 SLSTMKAIVECAGGKVLSKQPSFRKLMEHKQNSSLSEIILISCENDLHLCREYFARGI
                 DVHNAEFVLTGVLTQTLDYESYKFN

[0427] Further analysis of the NOV25a protein yielded the following properties shown in Table 25B.

TABLE 25B
Protein Sequence Properties NOV25a
PSort     0.9400 probability located in nucleus; 0.1000 probability
analysis: located in mitochondrial matrix space; 0.1000 probability
          located in lysosome (lumen); 0.0000 probability
          located in endoplasmic reticulum (membrane)
SignalP   No Known Signal Sequence Predicted
analysis:

[0428] 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 25C.

TABLE 25C
Geneseq Results for NOV25a
		NOV25a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAU27822	Human full-length polypeptide	466 . . . 1069	535/610 (87%)	0.0
	sequence #147 - Homo sapiens,	314 . . . 911	546/610 (88%)
	911 aa. [WO200164834-A2, 07-SEP-2001]
ABB71695	Drosophila melanogaster	385 . . . 1064	244/730 (33%)	2e−91
	polypeptide SEQ ID NO: 41877 -	1073 . . . 1777	355/730 (48%)
	Drosophila melanogaster, 1798 aa.
	[WO200171042-A2, 27-SEP-2001]
ABB58382	Drosophila melanogaster	342 . . . 586	93/258 (36%)	3e−25
	polypeptide SEQ ID NO: 1938 -	31 . . . 267	116/258 (44%)
	Drosophila melanogaster, 3502 aa.
	[WO200171042-A2, 27-SEP-2001]
ABB71160	Drosophila melanogaster	208 . . . 590	110/401 (27%)	7e−24
	polypeptide SEQ ID NO: 40272 -	3557 . . . 3949	167/401 (41%)
	Drosophila melanogaster, 5560 aa.
	[WO200171042-A2, 27-SEP-2001]
ABB65772	Drosophila melanogaster	208 . . . 590	110/401 (27%)	7e−24
	polypeptide SEQ ID NO: 24108 -	3557 . . . 3949	167/401 (41%)
	Drosophila melanogaster, 5533 aa.
	[WO200171042-A2, 27-SEP-2001]

[0429] In a BLAST search of public sequence datbases, the NOV25a protein was found to have homology to the proteins shown in the BLASTP data in Table 25D.

TABLE 25D
Public BLASTP Results for NOV25a
		NOV25a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9Z0W6	PAX TRANSCRIPTION	1 . . . 1069	916/1077	(85%)	0.0
	ACTIVATION DOMAIN	1 . . . 1056	960/1077	(89%)
	INTERACTING PROTEIN PTIP
	- Mus musculus (Mouse), 1056 aa.
O15404	CAGF28 - Homo sapiens	466 . . . 1069	514/610	(84%)	0.0
	(Human), 744 aa (fragment).	147 . . . 744	529/610	(86%)
Q90WJ3	SWIFT - Xenopus laevis (African	333 . . . 1068	513/795	(64%)	0.0
	clawed frog), 1256 aa.	472 . . . 1255	575/795	(71%)
Q96HP2	UNKNOWN (PROTEIN FOR	679 . . . 1069	391/391	(100%)	0.0
	IMAGE:3503689) - Homo sapiens	1 . . . 391	391/391	(100%)
	(Human), 391 aa (fragment).
Q9VUB6	CG8797 PROTEIN - Drosophila	385 . . . 1064	244/730	(33%)	4e−91
	melanogaster (Fruit fly), 1798 aa.	1073 . . . 1777	355/730	(48%)

[0430] PFam analysis predicts that the NOV25a protein contains the domains shown in the Table 25E.

TABLE 25E
Domain Analysis of NOV25a
		Identifies/
		Similarities
	NOV25a	for the
Pfam Domain	Match Region	Matched Region	Expect Value
BRCT	10 . . . 93	15/101	(15%)	1.2e−08
		59/101	(58%)
BRCT	96 . . . 183	35/101	(35%)	2.3e−25
		64/101	(63%)
BRCT	603 . . . 694	24/102	(24%)	1.8e−17
		69/102	(68%)
BRCT	703 . . . 776	25/88	(28%)	2.3e−18
		64/88	(73%)
BRCT	869 . . . 947	23/93	(25%)	1.9e−17
		67/93	(72%)
BRCT	970 . . . 1053	19/98	(19%)	0.27
		56/98	(57%)

Example 26

[0431] The NOV26 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 26A.

TABLE 26A
NOV26 Sequence Analysis
             SEQ ID NO:55        368 bp
NOV26a,      GATGAAATTCGTGTACAAAGAAGAGCATCCGTTCAAGAAACGGGCGTCCGAGAGCAAG
CG108762-01  AAGACTGGAAAGAAATACCCGGACCGGGTGCCGGTGATAGTAGAAAAGGCTCCCAAAG
DNA Sequence CTCGGATAGGAGACCTGGACCAAAAGAAATACCTGGTGCCTTCTGATCTCACAGCTGG
             TCAGTTCTACTTCTTGATCCAGAAGCGAATTCATCTCCGAGCTGAGGATGCCTTGTTT
             TTCTTTGTCAACAATGTCATTCTGCCCACCAGTGCCACAATGGGTCAGCTCTACCAGG
             AACACCATGAAGACTTCTTTCTCTACGTTGCCTACAGTGACCAAAGTGTCTACAGTCT
             GTGATGCTGCTACCCCTGAG
             ORF Start: ATG at 2 ORF Stop: TGA at 350
             SEQ ID NO:56        116 aa MW at 13595.5 kD
NOV26a,      MKFVYKEEHPFKKRASESKKTGKKYPDRVPVIVEKAPKARIGDLDQKKYLVPSDLTAG
CG108762-01  QFYFLIQKRIHLRAEDALFFFVNNVILPTSATMGQLYQEHHEDFFLYVAYSDQSVYSL
Protein Sequence

[0432] Further analysis of the NOV26a protein yielded the following properties shown in Table 26B.

TABLE 26B
Protein Sequence Properties NOV26a
PSort     0.6400 probability located in microbody (peroxisome);
analysis: 0.4500 probability
          located in cytoplasm; 0.1000 probability located in mito-
          chondrial matrix
          space; 0.1000 probability located in lysosome (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0433] 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.

TABLE 26C
Geneseq Results for NOV26a
		NOV26a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAG03859	Human secreted protein, SEQ ID	1 . . . 116	103/117	(88%)	9e−55
	NO: 7940 - Homo sapiens, 117 aa.	1 . . . 117	109/117	(93%)
	[EP1033401-A2, 06 Sep. 2000]
AAG03857	Human secreted protein, SEQ ID	1 . . . 116	103/117	(88%)	9e−55
	NO: 7938 - Homo sapiens, 117 aa.	1 . . . 117	109/117	(93%)
	[EP1033401-A2, 06 Sep. 2000]
ABB58226	Drosophila melanogaster	1 . . . 116	94/117	(80%)	4e−50
	polypeptide SEQ ID NO 1470 -	1 . . . 117	104/117	(88%)
	Drosophila melanogaster, 121 aa.
	[WO200171042-A2, 27 Sep. 2001]
AAM00990	Human bone marrow protein, SEQ	1 . . . 114	90/115	(78%)	9e−48
	ID NO: 491 - Homo sapiens, 117	1 . . . 115	102/115	(88%)
	aa. [WO200153453-A2, 26 Jul.
	2001]
AAM00943	Human bone marrow protein, SEQ	1 . . . 114	90/115	(78%)	9e−48
	ID NO: 419 - Homo sapiens, 144	28 . . . 142	102/115	(88%)
	aa. [WO200153453-A2, 26 Jul.
	2001]

[0434] In a BLAST search of public sequence datbases, the NOV26a protein was found to have homology to the proteins shown in the BLASTP data in Table 26D.

TABLE 26D
Public BLASTP Results for NOV26a
		NOV26a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
O95166	MM46 (HT004 PROTEIN) (MAP1	1 . . . 116	103/117	(88%)	2e−54
	LIGHT CHAIN 3 RELATED	1 . . . 117	109/117	(93%)
	PROTEIN) - Homo sapiens (Human),
	117 aa.
Q9DCD6	GAMMA-AMINOBUTYRIC ACID	1 . . . 116	103/117	(88%)	4e−54
	RECEPTOR ASSOCIATED	1 . . . 117	108/117	(92%)
	PROTEIN - Mus musculus (Mouse),
	117 aa.
Q9DFN7	GABA(A) RECEPTOR	1 . . . 114	99/115	(86%)	6e−52
	ASSOCIATED PROTEIN -	1 . . . 115	105/115	(91%)
	Gillichthys mirabilis (Long-jawed
	mudsucker), 122 aa.
Q9W2S2	CG1534 PROTEIN - Drosophila	1 . . . 116	94/117	(80%)	1e−49
	melanogaster (Fruit fly), 121 aa.	1 . . . 117	104/117	(88%)
Q9H0R8	HYPOTHETICAL 14.0 KDA	1 . . . 114	90/115	(78%)	2e−47
	PROTEIN (GABA-A RECEPTOR-	1 . . . 115	102/115	(88%)
	ASSOCIATED PROTEIN LIKE 1)
	(EARLY ESTROGEN-
	REGULATED PROTEIN) (RIKEN
	CDNA 9130422N19 GENE) - Homo
	sapiens (Human), 117 aa.

[0435] PFam analysis predicts that the NOV26a protein contains the domains shown in the Table 26E.

TABLE 26E
Domain Analysis of NOV26a
		Identities/
	NOV26a	Similarities for
Pfam Domain	Match Region	the Matched Region	Expect Value
MAP1_LC3	13 . . . 115	59/106 (56%)	1.4e−57
		89/106 (84%)

Example 27

[0436] The NOV27 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 27A.

TABLE 27A
NOV27 Sequence Analysis
                 SEQ ID NO:57          1504 bp
NOV27a,          ACGCGTCCGGTTCGCTCTGAGTCGCGTGGCAGGCCGCGCTGCGTCCACCGCTGCCGAG
CG108829-01      TTCAGAGCCGCGCACCGCCCGCCGCCGCAGGTCGGGTTCCCAGCGCTACTCCCAAGAC
DNA Sequence     ACCGCTCAGCCATGAAGATGCATTTCTGTATCCCGGTGTCCCAGCAGCGGTCCGACGC
                 GCTGGGGGGCCGCTACGTGCTGTACTCCGTGCACCTGGACGGGTTCCTCTTCTGCAGG
                 GTGCGCTACAGCCAGCTGCACGGTTGGAACGAACAGCTAAGGCGGGTCTTTGGAAATT
                 GCCTGCCACCCTTCCCACCAAAGTACTATCTGGCAATGACCACAGCTATGGCTGATGA
                 GAGGAGGGACCAACTGGAACAATATTTGCAAAATGTAACCATGGACCCAAACGTGTTG
                 AGAAGTGATGTCTTCGTTGAGTTTTTAAAACTGGCGCAGCTGAATACATTTGACATCG
                 CCACCAAGAAAGCTTATCTGGACATATTTCTGCCCAATGAACAGAGTATTAGAATCGA
                 AATTATAACATCAGACACTGCTGAAAGAGTCCTAGAGGTGGTGTCACACAAAATTGGA
                 CTGTGTCGAGAGCTCTTGGGCTACTTCGGCCTCTTTCTCATTCGGTTTGGCAAGGAGG
                 GCAAGCTCTCTGTTGTGAAAAAATTGGCTGACTTTGAACTCCCTTATGTTAGTCTTGG
                 AAGTTCTGAGGTGGAAAACTGTAAGGTTGGACTCCGAAAGTGGTATATGGCTCCATCC
                 CTCGACTCCGTGCTGATGGACTGCAGGGTGGCGGTAGATTTGCTCTACATGCAGGCAA
                 TACAGGACATTGAAAAAGGATGGGCCAAACCCACACAGGCACAGAGGCAGAAATTAGA
                 AGCTTTCCAGAAAGAAGACAGTCAAACAAAGTTTTTGGAGCTGGCCCGGGAGGTACGG
                 CACTATGGATACCTGCAGCTGGATCCTTGTACCTGTGACTACCCAGAATCAGGCTCTG
                 GAGCTGTTCTTTCTGTTGGCAATAATGAGATCAGCTGCTGCATCACCCTGCCTGACAG
                 CCAGACCCAGGACATCGTTTTCCAGATGAGCAGGGTGAAGTGCTGGCAGGTCACTTTC
                 CTTGGAACTCTGCTGGATACGGATGGGCCCCAGAGAACTCTCAACCAGAACTTAGAGC
                 TCAGATTTCAATACAGTGAGGATAGTTGCTGGCAGTGGTTTGTTATTTACACCAAACA
                 GGCTTTTTTGCTGAGTAGTTGCTTGAAAAAGATGATCTCAGAAAAGATGGTAAAGCTA
                 GCTGCTGAGAATACAGAAATGCAGATTGAAGTTCCGGAACAAAGCAAAAGTAAAAAAT
                 ACCACATTCAACAAAGCCAGAAAGACTATTCTAGTTTTCTATCAAGAAAAAGCAAGAT
                 TAAGATAGCTAAAGGTGACTGCGTTTTTGGGAACATAAAGGAAGAAGATCTCTGAAGA
                 AAGCTCTCATATTTTAAAATATCCTTGGAGGCTATCTCAAGACAGTGAAAGAAC
                 ORF Start: ATG at 128 ORF Stop: TGA at 1445
                 SEQ ID NO:58          439 aa MW at 50614.8 kD
NOV27a,          MKMHFCIPVSQQRSDALGGRYVLYSVHLDGFLFCRVRYSQLHGWNEQLRRVFGNCLPP
CG108829-01      FPPKYYLAMTTAMADERRDQLEQYLQNVTMDPNVLRSDVFVEFLKLAQLNTFDIATKK
Protein Sequence AYLDIFLPNEQSIRIEIITSDTAERVLEVVSHKIGLCRELLGYFGLFLIRFGKEGKLS
                 VVKKLADFELPYVSLGSSEVENCKVGLRKWYMAPSLDSVLMDCRVAVDLLYMQAIQDI
                 EKGWAKPTQAQRQKLEAFQKEDSQTKFLELAREVRHYGYLQLDPCTCDYPESGSGAVL
                 SVGNNEISCCITLPDSQTQDIVFQMSRVKCWQVTFLGTLLDTDGPQRTLNQNLELRFQ
                 YSEDSCWQWFVIYTKQAFLLSSCLKKMISEKMVKLAAENTEMQIEVPEQSKSKKYHIQ
                 QSQKDYSSFLSRKSKIKIAKGDCVFGNIKEEDL

[0437] Further analysis of the NOV27a protein yielded the following properties shown in Table 27B.

TABLE 27B
Protein Sequence Properties NOV27a
PSort     0.4500 probability located in cytoplasm; 0.1000 probability
analysis: located in mitochondrial matrix space;
          0.1000 probability located in lysosome (lumen);
          0.0782 probability located in microbody (peroxisome)
SignalP   No Known Signal Sequence Predicted
analysis:

[0438] 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.

TABLE 27C
Geneseq Results for NOV27a
		NOV27a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
ABB61758	Drosophila melanogaster	2 . . . 400	133/416	(31%)	5e−52
	polypeptide SEQ ID NO 12066 -	5 . . . 407	222/416	(52%)
	Drosophila melanogaster, 490 aa.
	[WO200171042-A2, 27 Sep. 2001]
AAB54165	Human pancreatic cancer antigen	20 . . . 253	104/235	(44%)	6e−52
	protein sequence SEQ ID NO:617 -	50 . . . 284	153/235	(64%)
	Homo sapiens, 288 aa.
	[WO200055320-A1, 21 Sep. 2000]
ABB59662	Drosophila melanogaster	18 . . . 379	87/368	(23%)	1e−20
	polypeptide SEQ ID NO 5778 -	82 . . . 424	160/368	(42%)
	Drosophila melanogaster, 431 aa.
	[WO200171042-A2, 27 Sep. 2001]
AAM41948	Human polypeptide SEQ ID NO	95 . . . 378	65/289	(22%)	3e−15
	6879 - Homo sapiens, 280 aa.	7 . . . 272	126/289	(43%)
	[WO200153312-A1, 27 Jul. 2001]
AAM40162	Human polypeptide SEQ ID NO	119 . . . 378	59/265	(22%)	5e−14
	3307 - Homo sapiens, 284 aa.	20 . . . 263	115/265	(43%)
	[WO200153312-A1, 26 Jul. 2001]

[0439] In a BLAST search of public sequence datbases, the NOV27a protein was found to have homology to the proteins shown in the BLASTP data in Table 27D.

TABLE 27D
Public BLASTP Results for NOV27a
		NOV27a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9D690	4631426E05RIK PROTEIN	3 . . . 439	330/437	(75%)	0.0
	Mus musculus (Mouse), 436 aa.	1 . . . 436	381/437	(86%)
Q15036	Sorting nexin 17 - Homo sapiens	3 . . . 425	175/434	(40%)	6e−85
	(Human), 470 aa.	1 . . . 433	267/434	(61%)
AAH26571	SIMILAR TO SORTING NEXIN	3 . . . 425	175/434	(40%)	1e−84
	17 - Mus musculus (Mouse), 470	1 . . . 433	266/434	(60%)
	aa.
Q9VL28	CG5734 PROTEIN (LD15323P) -	2 . . . 400	133/416	(31%)	1e−51
	Drosophila melanogaster (Fruit	5 . . . 407	222/416	(52%)
	fly), 490 aa.
Q19532	Hypothetical 54.2 kDa protein	12 . . . 410	102/423	(24%)	2e−34
	F17H10.3 in chromosome X -	14 . . . 419	204/423	(48%)
	Caenorhabditis elegans, 463 aa.

[0440] PFam analysis predicts that the NOV27a protein contains the domains shown in the Table 27E.

TABLE 27E
Domain Analysis of NOV27a
		Identities/
	NOV27a	Similarities for
Pfam Domain	Match Region	the Matched Region	Expect Value
PX	1 . . . 105	30/133 (23%)	3.2e−09
		70/133 (53%)

Example 28

[0441] The NOV28 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 28A.

TABLE 28A
NOV28 Sequence Analysis
                 SEQ ID NO:59         3534 bp
NOV28a,          GAGCCCGGCCGGGATGAGAAGGTGACGCCGCCGGGGGCGCCACTCGCTTTGTGGGGGA
CG108861-01      AGATGCTCGCCTACTGCGTGCAGGATGCCACCGTGGTGGACGTGGAGAAGCGGAGGAA
DNA Sequence     CCCCTCCAAGCACTACGTGAGTACACCACAGGTATACATAATCAATGTGACCTGGTCT
                 GACTCCACCTCCCAGACTATCTACCGGAGGTACAGCAAGTTCTTTGACCTGCAGATGC
                 AGCTTTTGGATAAGTTTCCCATTGAAGGTGGCCAGAAGGACCCCAAGCAAAGGATCAT
                 CCCCTTCCTCCCAGGCAAGATCCTCTTCCGCAGAAGCCACATCCGGGACGTAGCTGTG
                 AAGAGACTGAAGCCCATCGATGAATACTGCCGGGCACTTGTCCGGCTGCCCCCCCACA
                 TCTCACAGTGTGACGAAGTCTTCCGGTTCTTCGAGGCTCGACCCGAGGATGTCAACCC
                 TCCAAAAGAGGACTATGGCAGTTCCAAGAGGAAATCAGTGTGGCTGTCCAGCTGGGCT
                 GAGTCGCCCAAGAAGGACGTGACAGGTGCCGACGCCACCGCCGAGCCCATGATCCTGG
                 AACAGTACGTGGTGGTGTCCAACTATAAGAAGCAGGAGAACTCGGAGCTGAGCCTCCA
                 GGCCGGGGAGGTGGTGGATGTCATCGAGAAGAACGAGAGCGGCTGGTGGTTCGTGAGC
                 ACTTCTGAGGAGCAGGGCTGGGTCCCTGCCACCTACCTGGAGGCCCAGAATGGTACTC
                 GGGATGACTCCGACATCAACACCTCTAAGACTGGAGAAGTGTCCAAGAGACGCAAGGC
                 CCATCTGCGGCGCCTGGATCGCCGGTGGACCCTGGGCGGGATGGTCAACAGGCAGCAC
                 AGCCGAGAGGAGAAGTATGTCACCGTGCAGCCTTACACCAGCCAAAGCAAGGACGAGA
                 TTGGCTTTGAGAAGGGCGTCACAGTGGAGGTGATCCGGAAGAATCTGGAAGGCTGGTG
                 GTATATCAGATACCTGGGCAAAGAGGGCTGGGCGCCAGCATCCTACCTGAAGAAGGCC
                 AAGGATGACCTGCCAACCCGGAAGAAGAACCTGGCCGGCCCAGTGGAGATCATTGGGA
                 ACATCATGGAGATCAGCAACCTGCTGAACAAGAAGGCGTCTGGGGACAAGGAAACTCC
                 ACCAGCCGAAGGCGAGGGCCATGAGGCCCCCATTGCCAAGAAGGAGATCAGCCTGCCC
                 ATCCTCTGCAATGCCTCCAATGGCAGTGCCGTGGGCGTTCCTGACAGGACTGTCTCCA
                 GGCTGGCCCAGGGCTCTCCAGCTGTGGCCAGGATTGCCCCTCAGCGGGCCCAGATCAG
                 CTCCCCGAACCTACGGACAAGACCTCCACCACGCAGAGAATCCAGCCTGGGGTTCCAA
                 CTGCCAAAGCCACCAGAGCCCCCTTCTGTTGAGGTGGAGTACTACACCATTGCCGAAT
                 TCCAGTCGTGCATTTCCGATGGCATCAGCTTTCGGGGTGGACAGAAGGCAGAGGTCAT
                 TGATAAGAACTCAGGTGGCTGGTGGTACGTGCAGATCGGTGAGAAGGAGGGCTGGGCC
                 CCCGCATCATACATCGATAAGCGCAAGAAGCCCAACCTGAGCCGCCGCACAAGCACGC
                 TGACCCGGCCCAAGGTGCCCCCGCCAGCACCCCCCAGCAAGCCCAAGGAGGCCGAGGA
                 GGGCCCTACGGGGGCCAGTGAGAGCCAGGACTCCCCGCGGAAGCTCAAGTATGAGGAG
                 CCTGAGTATGACATCCCTGCATTCGGCTTTGACTCAGAGCCTGAGCTGAGCGAGGAGC
                 CCGTGGAGGACAGAGCCTCAGGGGAGAGGCGGCCTGCCCAGCCCCACCGGCCCTCGCC
                 GGCCTCTTCTCTGCAGCGGGCCCGCTTCAAGGTGGGTGAGTCTTCAGAGGATGTGGCC
                 CTGGAAGAGGAGACCATCTATGAGAATGAGGGCTTCCGGCCATATGCAGAGGACACCC
                 TGTCAGCCAGAGGCTCCTCCGGGGACAGCGACTCCCCAGGCAGCTCCTCGCTGTCCCT
                 GACCAGGAAAAACTCCCCCAAATCAGGCTCCCCCAAGTCATCATCACTCCTAAAGCTC
                 AAGGCAGAGAAGAATGCCCAGGCAGAAATGGGGAAGAACCACTCCTCAGCCTCCTTTT
                 CCTCATCCATCACCATCAACACCACTTGCTGCTCCTCCTCTTCCTCCTCCTCCTCTTC
                 CTTGTCCAAAACCAGTGGCGACCTGAAGCCCCGCTCTGCTTCGGACGCAGGCATCCGC
                 GGCACTCCCAAGGTCAGGGCAAAGAAGGATGCTGATGCGAACGCTGGGCTGACCTCCT
                 GTCCCCGGGCCAAGCCATCGGTCCGGCCCAAGCCATTCCTAAACCGAGCAGAGTCGCA
                 GAGCCAAGAGAAGATGGACATCAGCACTTTACGGCGCCAGCTGAGACCCACAGGCCAG
                 CTCCGTGGAGGGCTCAAGGGCTCCAAGAGTGAGGATTCGGAGCTGCCCCCGCAGACGG
                 CCTCCGAGGCTCCCAGTGAGGGGTCTAGGAGAAGCTCATCCGACCTCATCACCCTCCC
                 AGCCACCACTCCCCCATGTCCCACCAAGAAGGAATGGGAAGGGCCAGCCACCTCGTAC
                 ATGACATGCAGCGCCTACCAGAAGGTCCAGGACTCGGAGATCAGCTTCCCCGCGGGCG
                 TGGAGGTGCAGGTGCTGGAGAAGCAGGAGAGCGGGTGGTGGTATGTGAGGTTTGGGGA
                 GCTGGAGGGCTGGGCCCCTTCCCACTATTTGGTGCTGGATGAGAACGAGCAACCTGAC
                 CCCTCTGGCAAAGAGCTGGACACAGTGCCCGCCAAGGGCAGGCAGAACGAAGGCAAAT
                 CAGACAGCCTGGAGAAGATCGAGAGGCGCGTCCAAGCACTGAACACCGTCAACCAGAG
                 CAAGAAGGCCACGCCCCCCATCCCCTCCAAACCTCCCGGGGGCTTCGGCAAGACCTCA
                 GGCACTCCAGCGGTGAAGATGAGGAACGGAGTGCGGCAGGTGGCGGTCAGGCCCCAGT
                 CGGTGTTTGTGTCCCCGCCACCCAAGGACAACAACCTGTCCTGCGCCCTGCGGAGGAA
                 TGAGTCACTCACGGCCACTGATGGCCTCCGAGGCGTCCGACGGAACTCCTCCTTTAGC
                 ACTGCTCGCTCCGCTGCCGCCGAGGCCAAGGGCCGCCTGGCCGAACGGGCTGCCAGCC
                 AGGGTTCAGACTCACCCCTACTGCCCGCCCAGCGCAACAGCATACCCGTGTCCCCTGT
                 GCGCCCCAAGCCCATCGAGAAGTCTCAGTTCATCCACAATAACCTCAAAGATGTGTAC
                 GTCTCTATCGCAGACTACGAGGGGGATGAGGAGACAGCAGGCTTCCAGGAGGGGGTGT
                 CCATGGAGGTTCTGGAGAGGAACCCTAATGGCTGGTGGTACTGCCAGATCCTGGATGG
                 TGTGAAGCCCTTCAAAGGCTGGGTGCCTTCCAACTACCTTGAGAAAAAGAACTAGCAG
                 AGGGCCTGGGCTCTTCCAGCCTCAGTGTGCCTCTCTGGCCGCCCACTGGATGAG
                 ORF Start: ATG at 61 ORF Stop: TAG at 3475
                 SEQ ID NO:60         1138 aa MW at 125800.4 kD
NOV28a,          MLAYCVQDATVVDVEKRRNPSKHYVSTPQVYIINVTWSDSTSQTIYRRYSKFFDLQMQ
CG108861-01      LLDKFPIEGGQKDPKQRIIPFLPGKILFRRSHIRDVAVKRLKPIDEYCRALVRLPPHI
Protein Sequence SQCDEVFRFFEARPEDVNPPKEDYGSSKRKSVWLSSWAESPKKDVTGADATAEPMILE
                 QYVVVSNYKKQENSELSLQAGEVVDVIEKNESGWWFVSTSEEQGWVPATYLEAQNGTR
                 DDSDINTSKTGEVSKRRKAHLRRLDRRWTLGGMVNRQHSREEKYVTVQPYTSQSKDEI
                 GFEKGVTVEVIRKNLEGWWYIRYLGKEGWAPASYLKKAKDDLPTRKKNLAGPVEIIGN
                 IMEISNLLNKKASGDKETPPAEGEGHEAPIAKKEISLPILCNASNGSAVGVPDRTVSR
                 LAQGSPAVARIAPQRAQISSPNLRTRPPPRRESSLGFQLPKPPEPPSVEVEYYTIAEF
                 QSCISDGISFRGGQKAEVIDKNSGGWWYVQIGEKEGWAPASYIDKRKKPNLSRRTSTL
                 TRPKVPPPAPPSKPKEAEEGPTGASESQDSPRKLKYEEPEYDIPAFGFDSEPELSEEP
                 VEDRASGERRPAQPHRPSPASSLQRARFKVGESSEDVALEEETIYENEGFRPYAEDTL
                 SARGSSGDSDSPGSSSLSLTRKNSPKSGSPKSSSLLKLKAEKNAQAEMGKNHSSASFS
                 SSITINTTCCSSSSSSSSSLSKTSGDLKPRSASDAGIRGTPKVRAKKDADANAGLTSC
                 PRAKPSVRPKPFLNRAESQSQEKMDISTLRRQLRPTGQLRGGLKGSKSEDSELPPQTA
                 SEAPSEGSRRSSSDLITLPATTPPCPTKKEWEGPATSYMTCSAYQKVQDSEISFPAGV
                 EVQVLEKQESGWWYVRFGELEGWAPSHYLVLDENEQPDPSGKELDTVPAKGRQNEGKS
                 DSLEKIERRVQALNTVNQSKKATPPIPSKPPGGFGKTSGTPAVKMRNGVRQVAVRPQS
                 VFVSPPPKDNNLSCALRRNESLTATDGLRGVRRNSSFSTARSAAAEAKGRLAERAASQ
                 GSDSPLLPAQRNSIPVSPVRPKPIEKSQFIHNNLKDVYVSIADYEGDEETAGFQEGVS
                 MEVLERNPNGWWYCQILDGVKPFKGWVPSNYLEKKN

[0442] Further analysis of the NOV28a protein yielded the following properties shown in Table 28B.

TABLE 28B
Protein Sequence Properties NOV28a
PSort     0.9600 probability located in nucleus; 0.3000 probability
analysis: located in microbody (peroxisome); 0.1000 probability
          located in mitochondrial matrix space; 0.1000 probability
          located in lysosome (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0443] A search of the NOV28a protein against the Genseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 28C.

TABLE 28C
Geneseq Results for NOV28a
		NOV28a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAU14174	Human novel protein #45 - Homo	171 . . . 1138	968/968 (100%)	0.0
	sapiens, 968 aa. [WO200155437-	1 . . . 968	968/968 (100%)
	A2, 02-AUG-2001]
AAU68543	Human novel cytokine encoded by	6 . . . 223	146/218 (66%)	8e−83
	cDNA 790CIP2D_4 #1 - Homo	7 . . . 204	175/218 (79%)
	sapiens, 215 aa. [WO200175093-
	A1, 11-OCT-2001]
AAM79155	Human protein SEQ ID NO: 1817 -	1 . . . 138	133/138 (96%)	3e−72
	Homo sapiens, 194 aa.	1 . . . 133	133/138 (96%)
	[WO200157190-A2, 09-AUG-2001]
AAM80139	Human protein SEQ ID NO: 3785 -	1 . . . 138	132/138 (95%)	1e−71
	Homo sapiens, 206 aa.	13 . . . 145	132/138 (95%)
	[WO200157190-A2, 09-AUG-2001]
ABG15716	Novel human diagnostic protein	6 . . . 140	101/135 (74%)	8e−56
	#15707 - Homo sapiens, 142 aa.	13 . . . 142	119/135 (87%)
	[WO200175067-A2, 11-OCT-2001]

[0444] 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.

TABLE 28D
Public BLASTP Results for NOV28a
		NOV28a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9H462	BA416N2.2 (SIMILAR TO	108 . . . 1138	1031/1031 (100%)	0.0
	MURINE FISH (AN SH3 AND	1 . . . 1031	1031/1031 (100%)
	PX DOMAIN-CONTAINING
	PROTEIN, AND SRC
	SUBSTRATE)) - Homo sapiens
	(Human), 1031 aa (fragment).
O89032	FISH PROTEIN - Mus musculus	1 . . . 1138	1032/1138 (90%)	0.0
	(Mouse), 1124 aa.	1 . . . 1124	1062/1138 (92%)
O43302	KIAA0418 PROTEIN - Homo	171 . . . 1138	940/968 (97%)	0.0
	sapiens (Human), 940 aa.	1 . . . 940	940/968 (97%)
Q9NTM6	BA541N10.2 (NOVEL PROTEIN	1 . . . 107	102/107 (95%)	5e−52
	(ORTHOLOG OF MOUSE FISH	1 . . . 102	102/107 (95%)
	PROTEIN)) - Homo sapiens
	(Human), 102 aa (fragment).
Q95MN0	NADPH OXIDASE P47-PHOX -	6 . . . 339	112/334 (33%)	3e−51
	Oryctolagus cuniculus (Rabbit),	6 . . . 294	176/334 (52%)
	391 aa.

[0445] PFam analysis predicts that the NOV28a protein contains the domains shown in the Table 28E.

TABLE 28E
Domain Analysis of NOV28a
	NOV28a	Identities/Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
PX	3 . . . 129	39/149 (26%)	2.4e−23
		105/149 (70%)
SH3	174 . . . 228	18/58 (31%)	1.9e−11
		43/58 (74%)
SH3	274 . . . 328	19/58 (33%)	3.9e−09
		42/58 (72%)
SH3	456 . . . 510	14/58 (24%)	7.1e−05
		36/58 (62%)
SH3	848 . . . 902	17/58 (29%)	2.5e−05
		39/58 (67%)
SH3	1080 . . . 1137	20/61 (33%)	0.0002
		46/61 (75%)

Example 29

[0446] The NOV29 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 29A.

TABLE 29A
NOV29 Sequence Analysis
                 SEQ ID NO:61        1441 bp
NOV29a,          AAAGATGTCTACTCTCCTGGAAAACATCTTTGCCATAATTAATCTTTTCAAGCAATAT
CG109523-01      TCAAAAAAAGATAAAAACACTGACACATTGAGTAAAAAAGAGCTGAAGGAACTTCTGG
DNA Sequence     AAAAGGAATTTCGGCAAATCCTGAAGAATCCAGATGACCCAGATATGGTTGATGTCTT
                 CATGGATCACTTGGATATAGACCACAACAAGAAAATTGACTTCACTGAGTTTCTTCTG
                 ATGGTATTCAAGTTGGCTCAAGCATATTATGAGTCTACCAGAAAAGAGAATTTACCGA
                 TATCAGGACACAAGCACAGAAAGCACAGTCATCATGATAAACATGAAGATAATAAACA
                 AAAGGGAATAAGGGAAGATCCAAGAGCCCAAGAGAAACAGGGGGGAAAAGGCATGAAT
                 CTAGTTCTGAAAAAAAAGAAAGAAAAGGATATTCACCTACTCATAGAGAAGAAGAATA
                 TGGAAAAAACCATCATAACTCAAGTAAAAAAGAGAAAAACAAGACTGAAAATACTAGA
                 TTAGGAGACAATAGGAAGAGGCTAAGTGAAAGACTTGAAGAGAAAGAAGACAATGAAG
                 AAGGAGTATATGATTATGAAAATACAGGAAGAATGACTCAAAAATGGATACAATCAGG
                 CCATATTGCCACATATTACACAATCCAGGATGAAGCCTATGACACCACTGATAGTCTA
                 TTAGAAGAAAACAAAATATATGAAAGATCAAGGTCATCTGATGGCAAATCATCATCTC
                 AAGTGAACAGGTCAAGACATGAAAATACAAGCCAGGTACCATTGCAGGAGTCCAGGAC
                 AAGAAAGCGTAGGGGATCCAGAGTTAGCCAGGACAGGGACAGCCAGGGACACTCAGAA
                 GACTCCGAGAGGCACTCTGGGTCGGCTTCCAGAAACCATCATGGATCTGCGTGGGAGC
                 AGTCAAGAGATGGCTCCAGACACCCCAGGTCCCATGATGAAGACAGAGCCAGTCATGG
                 GCACTCTGCAGACAGCTCCAGACAATCAGGCACTCGTCACGCAGAGGAAACTTCCTCT
                 CGTGGACAGACTGCATCATCCCATGAACAGGCAAGATCAAGTCCAGGAGAAAGACATG
                 GATCCCACCACCAGCTCCAGTCAGCAGACAGCTCCAGACACTCAGCCACTGGGCGCGG
                 GCAAGCTTCATCTGCAGTCAGCGATCGTGGACACCGGGGGTCTAGCGGTAGTCAGGCC
                 AGTGACAGTGAGGGACATTCAGAAAACTCAGACACACAATCAGTGTCGGCCCACGGAA
                 AGGCTGGGCTGAGACAGCAGAGCCACCAAGAGTCCACACGTGGCCGGTCAGCAGGAAC
                 GGTCTGGACGTTCAGGGTCTTCCCTCTACCAGGTGAGCTCTCATGAACA
                 ORF Start: ATG at 5 ORF Stop: TGA at 1436
                 SEQ ID NO:62        477 aa MW at 54535.2 kD
NOV29a,          MSTLLENIFAIINLFKQYSKKDKNTDTLSKKELKELLEKEFRQILKNPDDPDMVDVFM
CG109523-01      DHLDIDHNKKIDFTEFLLMVFKLAQAYYESTRKENLPISGHKHRKHSHHDKHEDNKQE
Protein Sequence ENRENRKRPSSLERRNNRKGNKGRSKSPRETGGKRHESSSEKKERKGYSPTHREEEYG
                 KNHHNSSKKEKNKTENTRLGDNRKRLSERLEEKEDNEEGVYDYENTGRMTQKWIQSGH
                 IATYYTIQDEAYDTTDSLLEENKIYERSRSSDGKSSSQVNRSRHENTSQVPLQESRTR
                 KRRGSRVSQDRDSQGHSEDSERHSGSASRNHHGSAWEQSRDGSRHPRSHDEDRASHGH
                 SADSSRQSGTRHAEETSSRGQTASSHEQARSSPGERHGSHHQLQSADSSRHSATGRGQ
                 ASSAVSDRGHRGSSGSQASDSEGHSENSDTQSVSAHGKAGLRQQSHQESTRGRSAGTV
                 WTFRVFPLPGELS

[0447] Further analysis of the NOV29a protein yielded the following properties shown in Table 29B.

TABLE 29B
Protein Sequence Properties NOV29a
PSort     0.5500 probability located in endoplasmic reticulum
analysis: (membrane); 0.1900 probability located in lysosome (lumen);
          0.1800 probability located in nucleus;
          0.1000 probability located in endoplasmic
          reticulum (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0448] A search of the NOV29a protein against the Genseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 29C.

TABLE 29C
Geneseq Results for NOV29a
		NOV29a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAY22956	Human filagrin sequence of clone	152 . . . 463	175/322 (54%)	5e−79
	HB2650 - Homo sapiens, 330 aa.	11 . . . 321	200/322 (61%)
	[WO9928344-A2, 10-JUN-1999]
AAY22954	Human filagrin sequence of clone	152 . . . 463	174/322 (54%)	1e−78
	HB2641 - Homo sapiens, 330 aa.	11 . . . 321	199/322 (61%)
	[WO9928344-A2, 10-JUN-1999]
AAY22957	Human filagrin sequence of clone	102 . . . 463	175/362 (48%)	4e−78
	HB2648 - Homo sapiens, 330 aa.	28 . . . 321	211/362 (57%)
	[WO9928344-A2, 10-JUN-1999]
AAY22955	Human filagrin sequence of clone	152 . . . 463	173/322 (53%)	6e−78
	HB2642 - Homo sapiens, 330 aa.	11 . . . 321	199/322 (61%)
	[WO9928344-A2, 10-JUN-1999]
AAM25257	Human protein sequence SEQ ID	1 . . . 206	80/210 (38%)	3e−31
	NO: 772 - Homo sapiens, 218 aa.	5 . . . 214	116/210 (55%)
	[WO200153455-A2, 26-JUL-2001]

[0449] 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 29D.

TABLE 29D
Public BLASTP Results for NOV29a
		NOV29a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q01720	FILAGGRIN PRECURSOR	1 . . . 460	454/460 (98%)	0.0
	(PROFILAGGRIN) - Homo	1 . . . 458	456/460 (98%)
	sapiens (Human), 591 aa
	(fragment).
Q9H4U2	DJ14N1.1.1 (PROFILAGGRIN 5′	1 . . . 460	454/460 (98%)	0.0
	END) - Homo sapiens (Human),	1 . . . 458	456/460 (98%)
	687 aa (fragment).
Q05331	FILAGGRIN (PROFILAGGRIN) -	1 . . . 462	434/462 (93%)	0.0
	Homo sapiens (Human), 1218 aa	1 . . . 460	443/462 (94%)
	(fragment).
A48118	major epidermal calcium-binding	2 . . . 307	296/306 (96%)	e−174
	protein profilaggrin - human, 306	1 . . . 306	301/306 (97%)
	aa (fragment).
Q03838	FILAGGRIN (PROFILAGGRIN) -	223 . . . 460	227/238 (95%)	e−125
	Homo sapiens (Human), 465 aa	1 . . . 236	229/238 (95%)
	(fragment).

[0450] PFam analysis predicts that the NOV29a protein contains the domains shown in the Table 29E.

TABLE 29E
Domain Analysis of NOV29a
	NOV29a	Identities/Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
S_100	4 . . . 47	27/44 (61%)	2.6e−19
		41/44 (93%)
efhand	53 . . . 81	9/29 (31%)	0.035
		23/29 (79%)

Example 30

[0451] The NOV30 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 30A.

TABLE 30A
NOV30 Sequence Analysis
                 SEQ ID NO:63         1247 bp
NOV30a,          CGGGAACCCCAACTGGAGTGGGTCCTCACTGTTCTCTTTTTCCTCTGGCAGCCTTGGA
CG109649-01      GCATGGCAAGTCCAGAGCACCCTGGGAGCCCTGGCTGCATGGGACCCATAACCCAGTG
DNA Sequence     CACGGCAAGGACCCAGCAGGAAGCACCAGCCACTGGCCCCGACCTCCCGCACCCAGGA
                 CCTGACGGGCACTTAGACACACACAGTGGCCTGAGCTCCAACTCCAGCATGACCACGC
                 GGGAGCTTCAGCAGTACTGGCAGAACCAGAAATGCCGCTGGAAGCACGTCAAACTGCT
                 CTTTGAGATCGCTTCAGCTCGCATCGAGGAGAGAAAAGTCTCTAAGTTTGTGGTGTAC
                 CAAATCATCGTCATCCAGACTGGGAGCTTTGACAACAACAAGGCCGTCCTGGAACGGC
                 GCTATTCCGACTTCGCGAAGCTCCAGAAAGCGCTGCTGAAGACGTTCAGGGAGGAGAT
                 CGAAGACGTGGAGTTTCCCAGGAAGCACCTGACTGGGAACTTCGCTGAGGAGATGATC
                 TGTGAGCGTCGGCGCGCCCTGCAGGAGTACCTGGGCCTGCTCTACGCCATCCGCTGCG
                 TGCGCCGCTCCCGGGAGTTCCTGGACTTCCTCACGCGGCCGGAGCTGCGCGAGGCTTT
                 CGGCTGCCTGCGGGCCGGCCAGTACCCGCGCGCCCTGGAGCTGCTGCTGCGCGTGCTG
                 CCGCTGCAGGAGAAGCTCACCGCCCACTGCCCTGCGGCCGCCGTCCCGGCCCTGTGCG
                 CCGTGCTGCTGTGCCACCGCGACCTCGACCGCCCCGCCGAGGCCTTCGCGGCCGGAGA
                 GAGGGCCCTGCAGCGCCTGCAGGCCCGGGAGGGCCATCGCTACTATGCGCCTCTGCTG
                 GACGCCATGGTCCGCCTGGCCTACGCGCTGGGCAAGGACTTCGTGACTCTGCAGGAGA
                 GGCTGGAGGAGAGCCAGCTCCGGAGGCCCACGCCCCGAGGCATCACCCTGAAGGAGCT
                 CACTGTGCGAGAATACCTGCACTGAGCCGGCCTGGGACCCCGCAGGGACGCTGGAGAT
                 TTGGGGTCACCATGGCTCACAGTGGGCTGTTTGGGGTTCTTTTTTTTTATTTTTCCTT
                 TTCTTTTTTGTTATTTGAGACAGTCTTGCTCTGTCACCCAGACTGAAGTGCAGTGGCT
                 CAATTATGTCTCACTGCAGCCTCAAACTCCTGGGCACAAGCAATCCTCCCACCTCAGC
                 CTCCCAAGTAGCTGGGATTACAGGTGCAG
                 ORF Start: ATG at 61 ORF Stop: TGA at 1009
                 SEQ ID NO:64         316 aa MW at 36177.2 kD
NOV30a,          MASPEHPGSPGCMGPITQCTARTQQEAPATGPDLPHPGPDGHLDTHSGLSSNSSMTTR
CG109649-01      ELQQYWQNQKCRWKHVKLLFEIASARIEERKVSKFVVYQIIVIQTGSFDNNKAVLERR
Protein Sequence YSDFAKLQKALLKTFREEIEDVEFPRKHLTGNFAEEMICERRRALQEYLGLLYAIRCV
                 RRSREFLDFLTRPELREAFGCLRAGQYPRALELLLRVLPLQEKLTAHCPAAAVPALCA
                 VLLCHRDLDRPAEAFAAGERALQRLQAREGHRYYAPLLDAMVRLAYALGKDFVTLQER
                 LEESQLRRPTPRGITLKELTVREYLH

[0452] Further analysis of the NOV30a protein yielded the following properties shown in Table 30B.

TABLE 30B
Protein Sequence Properties NOV30a
PSort     0.8500 probability located in endoplasmic reticulum
analysis: (membrane); 0.4400 probability located in plasma membrane;
          0.3000 probability located in microbody (peroxisome);
          0.1000 probability located in mitochondrial
          inner membrane
SignalP   No Known Signal Sequence Predicted
analysis:

[0453] 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.

TABLE 30C
Geneseq Results for NOV30a
		NOV30a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAG79225	Amino acid sequence of a human	1 . . . 316	316/316 (100%)	0.0
	PSGL-1 binding protein - Homo	1 . . . 316	316/316 (100%)
	sapiens, 316 aa. [WO200173028-
	A2, 04-OCT-2001]
AAG79120	Amino acid sequence of IBD1prox	1 . . . 316	316/316 (100%)	0.0
	protein - Homo sapiens, 334 aa.	19 . . . 334	316/316 (100%)
	[FR2806739-A1, 28-SEP-2001]
AAB43067	Human ORFX ORF2831	7 . . . 95	85/89 (95%)	4e−46
	polypeptide sequence SEQ ID	26 . . . 114	86/89 (96%)
	NO: 5662 - Homo sapiens, 148 aa.
	[WO200058473-A2, 05-OCT-2000]
AAM89008	Human immune/haematopoietic	1 . . . 58	58/58 (100%)	1e−29
	antigen SEQ ID NO: 16601 -	19 . . . 76	58/58 (100%)
	Homo sapiens, 156 aa.
	[WO200157182-A2, 09-AUG-2001]
ABG27894	Novel human diagnostic protein	1 . . . 44	44/44 (100%)	1e−21
	#27885 - Homo sapiens, 580 aa.	350 . . . 393	44/44 (100%)
	[WO200175067-A2, 11-OCT-2001]

[0454] In a BLAST search of public sequence datbases, the NOV30a protein was found to have homology to the proteins shown in the BLASTP data in Table 30D.

TABLE 30D
Public BLASTP Results for NOV30a
		NOV30a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
CAD10213	SEQUENCE 4 FROM PATENT	1 . . . 316	316/316 (100%)	0.0
	WO0172822 - Homo sapiens	19 . . . 334	316/316 (100%)
	(Human), 334 aa (fragment).
CAD10211	SEQUENCE 1 FROM PATENT	1 . . . 316	316/316 (100%)	0.0
	WO0173028 - Homo sapiens	1 . . . 316	316/316 (100%)
	(Human), 316 aa.
Q9D2Y5	Sorting nexin 20 - Mus musculus	1 . . . 315	244/315 (77%)	e−138
	(Mouse), 313 aa.	1 . . . 312	269/315 (84%)
Q969T3	Sorting nexin 21 - Homo sapiens	37 . . . 315	103/281 (36%)	4e−38
	(Human), 373 aa.	100 . . . 372	145/281 (50%)
Q8WY78	PP3993 - Homo sapiens	138 . . . 315	69/180 (38%)	2e−21
	(Human), 184aa.	4 . . . 183	94/180 (51%)

[0455] PFam analysis predicts that the NOV30a protein contains the domains shown in the Table 30E.

TABLE 30E
Domain Analysis of NOV30a
		NOV30a	Identities/
	Pfam	Match	Similarities	Expect
	Domain	Region	for the Matched Region	Value
	PX	78 . . . 187	34/140 (24%)	3.1e−16
			82/140 (59%)

Example 31

[0456] The NOV31 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 3 1A.

TABLE 31A
NOV31 Sequence Analysis
                 SEQ ID NO:65         867 bp
NOV31a,          GGAACTCGGGCTAGCTAAGGAGGCCATTCTTGATGTTGCTTCTAGATCTCATGTCATC
CG110063-01      ACCGAGCCCTCAGCTGCTGGTGGCAGCTGCTCAGCAGACCCTTGGCATGGGAAAGAGA
DNA Sequence     CGGAGTCCACCCCAAGCCATCTGCCTTCACTTAGCTGGAGAGGTGCTGGCTGTGGCCC
                 GGGGACTGAAGCCAGCTGTGCTCTATGATTGCAACTGTGCAGGGGCATCAGAGCTCCA
                 GAGCTATCTGGAGGAGCTGAAGGGGCTTGGCTTCCTGACTTTTGGACTTCACATCCTT
                 GAGATTGGAGAAAACAGCCTGATTGTCAGTCCTGAGCATGTATGTCAGCACTTGGAGC
                 AGGTGCTGCTTGGTACCATAGCCTTTGTGGATGTTTCCAGCTGCCAGCGTCACCCTTC
                 TGTCTGCTCCCTGGACCAGCTTCAGGACTTGAAGGCCCTCGTGGCTGAGATCATCACA
                 CATTTGCAGGGGCTGCAGAGGGACTTATCTCTAGCAGTCTCCTACAGCAGGCTCCATT
                 CCTCAGACTGGAATCTGTGTACTGTATTTGGGATCCTCCTGGGCTATCCTGTTCCCTA
                 TACCTTTCACCTGAACCAGGGAGATGACAACTGCTTAGCTCTGACTCCACTACGAGTA
                 TTCACTGCCCGGATCTCATGGTTGCTAGGTCAACCCCCAATCCTGCTCTATTCTTTTA
                 GTGTCCCACAGAGTTTGTTCCCAGGCCTGAGGGACATTCTAAACACCTGGGAGAAGGA
                 CCTCAGAACCCGATTTAGGACTCAGAATGACTTTGCTGATCTCAGCATCTCCTCTGAG
                 ATAGTCACACTGCCGGCTGTGGCCCTCTGACTTTAACTCTCCTCCCATATAGAAG
                 ORF Start: ATG at 33 ORF Stop: TGA at 840
                 SEQ ID NO:66         269 aa MW at 29560.8 kD
NOV31a,          MLLLDLMSSPSPQLLVAAAQQTLGMGKRRSPPQAICLHLAGEVLAVARGLKPAVLYDC
CG110063-01      NCAGASELQSYLEELKGLGFLTFGLHILEIGENSLIVSPEHVCQHLEQVLLGTIAFVD
Protein Sequence VSSCQRHPSVCSLDQLQDLKALVAEIITHLQGLQRDLSLAVSYSRLHSSDWNLCTVFG
                 ILLGYPVPYTFHLNQGDDNCLALTPLRVFTARISWLLGQPPILLYSFSVPESLFPGLR
                 DILNTWEKDLRTRFRTQNDFADLSISSEIVTLPAVAL
                 SEQ ID NO:67         856 bp
NOV31b,          CTAGCTAAGGAGGCCATTCTTGATGTTGCTTCTAGATCTCATGTCATCACCGAGCCCT
CG110063-02      CAGCTGCTGGTGGCAGCTGCTCAGCAGACCCTTGGCATGGGAAAGAGACGGAGTCCAC
DAN Sequence     CCCAAGCCATCTGCCTTCACTTAGCTGGAGAGGTGCTGGCTGTGGCCCGGGGACTGAA
                 GCCAGCTGTGCTCTATGATTGCAACTGTGCAGGGGCATCAGAGCTCCAGAGCTATCTG
                 GAGGAGCTGAAGGGGCTTGGCTTCCTGACTTTTGGACTTCACATCCTTGAGATTGGAG
                 AAAACAGCCTGATTGTCAGTCCTGAGCATGTATGTCAGCACTTGGAGCAGGTGCTGCT
                 TGGTACCATAGCCTTTGTGGATGTTTCCAGCTGCCAGCGTCACCCTTCTGTCTGCTCC
                 CTGGACCAGCTTCAGGACTTGAAGGCCCTCGTGGCTGAGATCATCACACATTTGCAGG
                 GGCTGCAGAGGGACTTATCTCTAGCAGTCTCCTACAGCAGGCTCCATTCCTCAGACTG
                 GAATCTGTGTACTGTATTTGGGATCCTCCTGGGCTATCCTGTTCCCTATACCTTTCAC
                 CTGAACCAGGGAGATGACAACTGCTTAGCTCTGACTCCACTACGAGTATTCACTGCCC
                 GGATCTCATGGTTGCTAGGTCAACCCCCAATCCTGCTCTATTCTTTTAGTGTCCCAGA
                 GAGTTTGTTCCCAGGCCTGAGGGACATTCTAAACACCTGGGAGAAGGACCTCAGAACC
                 CGATTTAGGACTCAGAATGACTTTGCTGATCTCAGCATCTCCTCTGAGATAGTCACAC
                 TGCCGGCTGTGGCCCTCTGACTTTAACTCTCCTCCCATATAGAA
                 ORF Start: ATG at 23 ORF Stop: TGA at 830
                 SEQ ID NO:68         269 aa MW at 29560.8 kD
NOV31b.          MLLLDLMSSPSPQLLVAAAQQTLGMGKRRSPPQAICLHLAGEVLAVARGLKPAVLYDC
CG110063-02      NCAGASELQSYLEELKGLGFLTFGLHILEIGENSLIVSPEHVCQHLEQVLLGTIAFVD
Protein Sequence VSSCQRHPSVCSLDQLQDLKALVAEIITHLQGLQRDLSLAVSYSRLHSSDWNLCTVFG
                 ILLGYPVPYTFHLNQGDDNCLALTPLRVFTARISWLLGQPPILLYSFSVPESLFPGLR
                 DILNTWEKDLRTRFRTQNDFADLSISSEIVTLPAVAL

[0457] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 31B.

TABLE 31B
Comparison of NOV31a against NOV31b.
Protein	NOV31a Residues/	Identities/
Sequence	Match Residues	Similarities for the Matched Region
NOV31b	16 . . . 269	254/254 (100%)
	16 . . . 269	254/254 (100%)

[0458] Further analysis of the NOV31a protein yielded the following properties shown in Table 31C.

TABLE 31C
Protein Sequence Properties NOV31a
PSort     0.3600 probability located in mitochondrial matrix space; 0.3000 probability
analysis: located in microbody (peroxisome); 0.2167 probability located in lysosome
          (lumen); 0.1000 probability located in nucleus
SignalP   No Known Signal Sequence Predicted
analysis:

[0459] 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 31D.

TABLE 31D
Geneseq Results for NOV31a
		NOV31a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAG75024	Human colon cancer antigen	1 . . . 107	107/107 (100%)	1e−55
	protein SEQ ID NO:5788 - Homo	7 . . . 113	107/107 (100%)
	sapiens, 113 aa. [WO200122920-
	A2, 05 Apr. 2001]
ABG07312	Novel human diagnostic protein	88 . . . 160	28/76 (36%)	5.6
	#7303 - Homo sapiens, 1132 aa.	131 . . . 205	34/76 (43%)
	[WO200175067-A2, 11 Oct. 2001]
ABG07312	Novel human diagnostic protein	88 . . . 160	28/76 (36%)	5.6
	#7303 - Homo sapiens, 1132 aa.	131 . . . 205	34/76 (43%)
	[WO200175067-A2, 11 Oct. 2001]

[0460] In a BLAST search of public sequence datbases, the NOV31a protein was found to have homology to the proteins shown in the BLASTP data in Table 31E.

TABLE 31E
Public BLASTP Results for NOV31a
		NOV31a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q96LT6	CDNA FLJ25078 FIS, CLONE	1 . . . 269	269/269 (100%)	e−153
	CBL06954 - Homo sapiens	1 . . . 269	269/269 (100%)
	(Human), 269 aa.
Q9DAE8	ADULT MALE TESTIS CDNA,	7 . . . 269	208/263 (79%)	e−118
	RIKEN FULL-LENGTH	1 . . . 263	232/263 (88%)
	ENRICHED LIBRARY,
	CLONE: 1700012B08, FULL
	INSERT SEQUENCE - Mus
	musculus (Mouse), 263 aa.

[0461] PFam analysis predicts that the NOV31a protein contains the domains shown in the Table 31F.

TABLE 31F
Domain Analysis of NOV31a
	Pfam	NOV31a	Identities/	Expect
	Domain	Match	Similarities	Value
		Region	for the Matched Region

Example 32

[0462] The NOV32 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 32A.

TABLE 32A
NOV32 Sequence Analysis
                 SEQ ID NO:69         684 bp
NOV32a           CCCGCTCCGGCCGGGACGATGGTGAAGTATTTCCTGGGCCAGAGCGTGCAACGGAGCT
CG110151-01      CCTGGGACCAAGTGTTCGCCGCCTTCTGGCAGCGGTACCCGAATCCCTATAGCAAACA
DNA Sequence     TGTCTTGACGGAAGACGTAGTACACCGGGAGGTAACCCCTGACCAGAAACTGCTGTCC
                 GGGCGACTCCTGACCAAGACCAACAGGACGCCCTGCTGGGCCGAGCGACTGTTTCCTG
                 CCAATGTTGATCACTCGGTGTACATCCTGGAGGACTCTATTGTGGACCCACAGAATCA
                 GACCATGACCACCTTCACCTGGAACATCAACCATGCCCGGCTGATGGTGGTGGAGGAA
                 CGATGTGTTTACTGTGTGAACTCTGACAACAGTGGCCGGACCGAAATCCGCCGGGAAG
                 CCTGGGTCTCCTCTAGCTTATTTGGTGTCTCCAGAGCTGTCCAGGAATTTGGTCTTGC
                 CTGGTTCAAAAGCAATGTGACCAAGACTATGAAGGGTTTTGAATATATCTTGGCAAAG
                 CTGCAAGGCGAGGCCCCTTCCAAAACACTTGTTGAGACAGCCAAGGAAGCCAAGGAGA
                 AGGCAAAGGAGACAGCACTGGCAGCTACAGAGAAGGCCAAGGACCTCGCCAGCAAGGC
                 AGCCACCAAGAAGCAGCAGCAGCAGCAACAGTTTGTGTAGCCAGCC
                 ORF Start: ATG at 19 ORF Stop: TAG at 676
                 SEQ ID NO:70         219 aa MW at 25057.3 kD
NOV32a,          MVKYFLGQSVQRSSWDQVFAAFWQRYPNPYSKHVLTEDVVHREVTPDQKLLSGRLLTK
CG110151-01      TNRTPCWAERLFPANVDHSVYILEDSIVDPQNQTMTTFTWNINHARLMVVEERCVYCV
Protein Sequence NSDNSGRTEIRREAWVSSSLFGVSRAVQEFGLAWFKSNVTKTMKGFEYILAKLQGEAP
                 SKTLVETAKEAKEKAKETALAATEKAKDLASKAATKKQQQQQQFV

[0463] Further analysis of the NOV32a protein yielded the following properties shown in Table 32B.

TABLE 32B
Protein Sequence Properties NOV32a
PSort     0.5714 probability located in microbody (peroxisome); 0.3600 probability
analysis: located in mitochondrial matrix space; 0.1000 probability located in lysosome
          (lumen); 0.0000 probability located in endoplasmic reticulum (membrane)
SignalP   No Known Signal Sequence Predicted
analysis:

[0464] 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.

TABLE 32C
Geneseq Results for NOV32a
		NOV32a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAW61538	Human LEA-motif developmental	1 . . . 219	210/219 (95%)	e−117
	protein - Homo sapiens, 219 aa.	1 . . . 219	212/219 (95%)
	[WO9835041-A1, 13 Aug. 1998]
ABG09766	Novel human diagnostic protein	1 . . . 214	144/214 (67%)	3e−69
	#9757 - Homo sapiens, 167 aa.	1 . . . 167	152/214 (70%)
	[WO200175067-A2, 11 Oct. 2001]
ABG09766	Novel human diagnostic protein	1 . . . 214	144/214 (67%)	3e−69
	#9757 - Homo sapiens, 167 aa.	1 . . . 167	152/214 (70%)
	[WO200175067-A2, 11 Oct. 2001]
ABB12426	Human bone marrow expressed	26 . . . 101	63/77 (81%)	5e−30
	protein SEQ ID NO: 265 - Homo	19 . . . 95	66/77 (84%)
	sapiens, 99 aa. [WO200174836-
	A1, 11 Oct. 2001]
ABB59225	Drosophila melanogaster	18 . . . 106	48/89 (53%)	7e−17
	polypeptide SEQ ID NO 4467 -	3 . . . 87	58/89 (64%)
	Drosophila melanogaster, 171 aa.
	[WO200171042-A2, 27 Sep. 2001]

[0465] In a BLAST search of public sequence datbases, the NOV32a protein was found to have homology to the proteins shown in the BLASTP data in Table 32D.

TABLE 32D
Public BLASTP Results for NOV32a
		NOV32a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9Y255	PX19 (SBBI12) (PX19-LIKE	1 . . . 219	210/219 (95%)	e−117
	PROTEIN) - Homo sapiens	1 . . . 219	212/219 (95%)
	(Human), 219 aa.
Q9UJS9	PRELI - Homo sapiens (Human),	1 . . . 219	209/219 (95%)	e−116
	219 aa.	1 . . . 219	211/219 (95%)
AAH25859	SIMILAR TO PX19-LIKE	1 . . . 215	204/215 (94%)	e−114
	PROTEIN - Mus musculus	1 . . . 215	208/215 (95%)
	(Mouse), 217aa.
Q9UI13	PX19 PROTEIN - Homo sapiens	1 . . . 219	198/219 (90%)	e−108
	(Human), 208 aa.	1 . . . 208	200/219 (90%)
Q90673	PX19 - Gallus gallus (Chicken),	1 . . . 213	175/213 (82%)	2e−97
	215 aa.	1 . . . 213	189/213 (88%)

[0466] PFam analysis predicts that the NOV32a protein contains the domains shown in the Table 32E.

TABLE 32E
Domain Analysis of NOV32a
Pfam Domain	NOV32a	Identities/	Expect Value
	Match Region	Similarities
		for the
		Matched Region

Example 33

[0467] The NOV33 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 33A.

TABLE 33A
NOV33 Sequence Analysis
                 SEQ ID NO:71        932 bp
NOV33a,          GTCAAAATGCAGATCTTCGTGAAGACCCTGACTGGCAAGACCATCACCCTTGAAGTGG
CG110340-01      AGCCCAGTGACACCATCGAAAATGTGAAGGCCAATATCCAGGATAAGGAAGGCATCCT
DNA Sequence     CCCCGACCAGCAGAGGCTCATCTTTGCAGGCATGCAGCTAGAAGATGGCTGTACTCTT
                 TCTGACTACAACATCCAGAAAGAGTTGACCCTGTACCTGGTCCAGCGTCTGAGATGTG
                 GCATGCAGATCTTCGTGAAGACCCTGACTGGCAAGACCATCACCCTTGAAGTGGAGCC
                 CACTGACACCATCGAAAATGTGAAGGCCAATATCCAGGATAAGGAAGGCATCCTCCCC
                 GACCAGCAGAGGCTCATCTTTGCAGGCATGCAGCTAGAAGATGGCTGTACTCTTTCTG
                 ACTACAACATCCAGAAAGAGTTGACCCTGTACCTGGTCCAGCGTCTGAGATGTGGCAT
                 GCAGATCTTCGTGAAGACCCTGACTGGCAAGACCATCACCCTTGAAGTGGAGCCCAGT
                 GACACCATCGAAAATGTGAAGGCCAATATCCAGGATAAGGAAGGCATCCTCCCCGACC
                 AGCAGAGGCTCATCTTTGCAGGCATGCAGCTAGAAGATGGCTGTACTCTTTCTGACTA
                 CAACATCCAGAAAGAGTTGACCCTGTACCTGGTCCAGCGTCTGAGATGTGGCATGCAG
                 ATCTTCGTGAAGACCCTGACTGGCAAGACCATCACCCTTGAAGTGGAGCCCAGTGACA
                 CCATCGAAAATGTGAAGGCCAATATCCAGGATAAGGAAGCCATCCTCCCCGACCAGCA
                 GAGGCTCATCTTTGCAGGCATGCAGCTAGAAGATGGCTGTACTCTTTCTGACTACAAC
                 ATCCAGAAAGAGTTGACCCTGTACCTGGTCCAGCGTCTGAGATGTGGCTGTTAGTTCT
                 TCAG
                 ORF Start: ATG at 7 ORF Stop: TAG at 922
                 SEQ ID NO:72        305 aa MW at 34568.6 kD
NOV 33a,         MQIFVKTLTGKTITLEVEPSDTIENVKANIQDKEGILPDQQRLIFAGMQLEDGCTLSD
CG110340-01      YNIQKELTLYLVQRLRCGMQIFVKTLTGKTITLEVEPSDTIENVKANIQDKEGILPDQ
Protein Sequence QRLIFAGMQLEDGCTLSDYNIQKELTLYLVQRLRCGMQIFVKTLTGKTITLEVEPSDT
                 IENVKANIQDKEGILPDQQRLIFAGMQLEDGCTLSDYNIQKELTLYLVQRLRCGMQIF
                 VKTLTGKTITLEVEPSDTIENVKANIQDKEGILPDQQRLIFAGMQLEDGCTLSDYNIQ
                 KELTLYLVQRLRCGC

[0468] Further analysis of the NOV33a protein yielded the following properties shown in Table 33B.

TABLE 33B
Protein Sequence Properties NOV33a
PSort     0.6500 probability located in cytoplasm;
analysis: 0.1000 probability located in
          mitochondrial matrix space; 0.1000
          probability located in
          lysosome (lumen);
          0.0000 probability located in
          endoplasmic reticulum (membrane)
SignalP   No Known Signal Sequence Predicted
analysis:

[0469] 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.

TABLE 33C
Geneseq Results for NOV33a
		NOV33a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent #,	Match	the Matched	Expect
Identifier	Date]	Residues	Region	Value
ABB67303	Drosophila melanogaster	1 . . . 304	272/304 (89%)	e−144
	polypeptide SEQ ID NO: 28701 -	153 . . . 456	276/304 (90%)
	Drosophila melanogaster, 719 aa.
	[WO200171042-A2, 27-SEP-2001]
ABB65843	Drosophila melanogaster	1 . . . 304	272/304 (89%)	e−144
	polypeptide SEQ ID NO: 24321 -	153 . . . 456	276/304 (90%)
	Drosophila melanogaster, 719 aa.
	[WO200171042-A2, 27-SEP-2001]
AAB58753	Breast and ovarian cancer	1 . . . 304	272/304 (89%)	e−144
	associated antigen protein sequence	31 . . . 334	276/304 (90%)
	SEQ ID 461 - Homo sapiens, 390
	aa [WO200055173-A1, 21-SEP-2000]
AAW14848	Poly-Ubiquitin - Synthetic, 685 aa.	1 . . . 304	272/304 (89%)	e−144
	[JP09037779-A, FEB-10-1997]	381 . . . 684	276/304 (90%)
AAW14134	Human poly-ubiquitin protein -	1 . . . 304	272/304 (89%)	e−144
	Homo sapiens, 685 aa.	381 . . . 684	276/304 (90%)
	[JP09000263-A, 07-JAN-1997]

[0470] In a BLAST search of public sequence datbases, the NOV33a protein was found to have homology to the proteins shown in the BLASTP data in Table 33D.

TABLE 33D
Public BLASTP Results for NOV33a
		NOV33a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
O46543	POLYUBIQUITIN - Ovis aries	1 . . . 305	272/305 (89%)	e−144
	(Sheep), 305 aa.	1 . . . 305	277/305 (90%)
S29853	polyubiquitin 4 - bovine, 305	1 . . . 305	272/305 (89%)	e−144
	aa.	1 . . . 305	276/305 (90%)
Q9ET23	POLYUBIQUITIN C - Mus	1 . . . 304	272/304 (89%)	e−144
	musculus (Mouse), 886 aa.	381 . . . 684	276/304 (90%)
Q9ET24	POLYUBIQUITIN C - Mus	1 . . . 304	272/304 (89%)	e−144
	musculus (Mouse), 734 aa.	229 . . . 532	276/304 (90%)
S21083	polyubiquitin 5 - Chinese	1 . . . 304	272/304 (89%)	e−144
	hamster, 381 aa.	77 . . . 380	276/304 (90%)

[0471] PFam analysis predicts that the NOV33a protein contains the domains shown in the Table 33E.

TABLE 33E
Domain Analysis of NOV33a
		Identities/
		Similarities
Pfam Domain	NOV33a	for the	Expect Value
	Match Region	Matched Region
ubiquitin	1 . . . 74	51/83 (61%)	2.5e−36
		70/83 (84%)
ubiquitin	77 . . . 150	51/83 (61%)	2.5e−36
		70/83 (84%)
ubiquitin	153 . . . 226	51/83 (61%)	2.5e−36
		70/83 (84%)
ubiquitin	229 . . . 302	51/83 (61%)	2.5e−36
		70/83 (84%)

Example 34

[0472] The NOV34 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 34A.

TABLE 34A
NOV34 Sequence Analysis
                 SEQ ID NO:73           2955 bp
NOV34a,          TCGTGGTAGGGACTCTCCACCTACAATCACAATACCAGTAAATATAAATCATGCTGCT
CG139264-01      AGTGGTTCCTTCAGAGAATCTGTGGACGCTCAAGAGGAAATCAGGAAAGTGGACGAAG
DNA Sequence     AGAGCTACTTATGTTCATAAAGATGGACTAAATTCCACTGATCACATGGTGCCCGACA
                 CTGAAAGTTATGATGCAGTTGAAATCATCCGCAAGGTTGCAGTGCCTCCTCGCCTGTC
                 AGAGCACACACAGAGATATGAAGCGGCCAACCGAACTGTTCAAATGGCTGAAAATTTC
                 GTGAATGACCCTGAAAATCAAATAAACAGATGGTTCAGGGAATTTGAGCATGGCCCAG
                 TTTCTGAAGCAAAGTCAAATAGAAGAGTTTATGCAAAGGGAGAAACAAACCATAACAT
                 ACAACAAGAAAGTCGTACATTTGTAAGGAGGAATTTGGATTAACATCTTTAGGAAACA
                 CGAGTTTTACAGACTTTTCTTGCAAACATCCTAGAGAACTGCGAGAAAAGATTCCTGT
                 TAAGCAGCCCAGGATCTGCTCTGAAACCAGGTCTCTAAGTGAACATTTCTCAGGCATG
                 GATGCATTTGAGAGTCAAATTGTTGAGTCGAAGATGAAAACCTCTTCATCACATAGCT
                 CAGAAGCTGGCAAATCTGGCTGTGACTTCAAGCATGCCCCACCAACCTATGAGGATGT
                 CATTGCTGGACATATTTTAGATATCTCTGATTCACCTAAAGAAGTAAGAAAAAATTTT
                 CAAAAGACGTGGCAAGAGAGTGGAAGAGTTTTTAAAGGCCTGGGATATGCAACCGCAG
                 ATGCTTCTGCAACTGAGATGAGAACCACCTTCCAAGAGGAATCTGCATTTATAAGTGA
                 AGCTGCTGCTCCAAGACAAGGAAATATGTATACTTGGTCAAAAGACAGTTTATCCAAT
                 GGAGTGCCTAGTGGCAGACAAGCAGAATTTTCATAAGTCCTGCTTCCGATGCCACCAT
                 TGCAACAGTAAACTAAGTTTGGGGAAATTATGCATCACTTCATGGACAAATATACTGT
                 AAACCTCACTTTAAACAACTTTTCAAATCCAAAGGAAATTATGATGAAGGTTTTGGAC
                 ATAAGCAGCATAAAGATAGATGGAACTGCAAAAACCAAAGCAGATCAGTGGACTTTAT
                 TCCTAATGAAGAACCAAATATGTGTAAAAATATTGCAGAAAACACCCTTGTACCTGGA
                 GATCGTAATGAACATTTAGATGCTGGTAACAGTGAAGGGCAAAGGAATGATTTGAGAA
                 AATTAGGGGAAAGGGGAAAATTAAAAGTCATTTGGCCTCCTTCCAAGGAGATCCCTAA
                 GAAAACCTTACCCTTTGAGGAAGAGCTCAAAATGAGTAAACCTAAGTGGCCACCTGAA
                 ATGACAACCCTGCTATCCCCTGAATTTAAAAGTGAATCTCTGCTAGAAGATGTTAGAA
                 CTCCAGAAAATAAAGGACAAAGACAAGATCACTTTCCATTTTTGCAGCCTTATCTACA
                 GTCCACCCATGTTTGTCAGAAAGAGGATGTTATAGGAATCAAAGAAATGAAAATGCCT
                 GAAGGAAGAAAAGATGAAAAGAAGGAAGGAAGGAAGAATGTGCAAGATAGGCCGAGTG
                 AAGCTGAAGACACAAAGAGTAACAGGAAAAGTGCTATGGATCTTAATGACAACAATAA
                 TGTGATTGTGCAGAGTGCTGAAAAGGAGAAAAATGAAAAAACTAACCAAACTAATGGT
                 GCAGAAGTTTTACAGGTTACTAACACTGATGATGAGATGATGCCAGAAAATCATAAAG
                 AAAATTTGAATAAGAATAATAATAACAATTATGTAGCAGTCTCATATCTGAATAATTG
                 CAGGCAGAAGACATCTATTTTAGAATTTCTTGATCTATTACCCTTGTCGAGTGAAGCA
                 AATGACACTGCAAATGAATATGAAATTGAGAAGTTAGAAAATACATCTAGAATCTCAG
                 AGTTACTTGGTATATTTGAATCTGAAAAGACTTATTCGAGGAATGTACTAGCAATGGC
                 TCTGAAGAAACAGACTGACAGAGCAGCTGCTGGCAGTCCTGTGCAGCCTGCTCCAAAA
                 CCAAGCCTCAGCAGAGGCCTTATGGTAAAGGGGGGAAGTTCAATCATCTCTCCTGATA
                 CAAATCTCTTAAACATTAAAGGAAGCCATTCAAAGAGCAAAAATTTACACTTTTTCTT
                 TTCTAACACCGTGAAAATCACTGCATTTTCCAAGAAAAATGAGAACATTTTCAATTGT
                 GATTTAATAGATTCTGTAGATCAAATTAAAAATATGCCATGCTTGGATTTAAGGGAAT
                 TGGAAAGGATGTTAAACCTTGGCATGTTGAAACAACAGAAGCTGCCCGCAATAATGAA
                 AACACAGGTTTTGATGCTCTGAGCCATGAATGTACAGCTAAGCCTTTGTTTCCCAGAG
                 TGGAGGTGCAGTCAGAACAACTCACGGTGGAAGAGCAGATTAAAAGAAACAGGTGCTA
                 CAGTGACACTGAGTAAAATATCTATGGCCACTGACAGTCCACACTTAGGCACTGAGAG
                 ATATTGATGTTCTGAAATAAGATTTTATGAATTTGGATACCCTTTTGAGGAACTTGAT
                 GTAAACATGGTGTTCAGAAATCTCGTGTCTATCTCAATGGGATATTTCTTGTATTACA
                 CCTTGTCATTTTTTTCACAATTTATTTACATCTACTTTTGTTTGAACTGGAATGAAGA
                 GATGAAACACTATGGATATGTTTTCCATTCAAATGGCACTTTAGCATATTGTTCTGTT
                 TTCCTGTAAAACATCATGGGTGTGATTTTTATACTGCTGCTGCTTGTCACAATTATTA
                 TAACTTCTCTGTAATTTCCTCTGAAATAAAATTGAATCACCTGAGGTGCCAAACCAAA
                 AAAAAAATTCTATAACTTTTTTGATATAATACTGTCATTCTAAGTACATATGACT
                 ORF Start: ATG at 1180 ORF Stop: TGA at 2398
                 SEQ ID NO:74           406 aa MW at 46085.9 kD
NOV34a,          MCKNIAENTLVPGDRNEHLDAGNSEGQRNDLRKLGERGKLKVIWPPSKEIPKKTLPFE
CG139264-01      EELKMSKPKWPPEMTTLLSPEFKSESLLEDVRTPENKGQRQDHFPFLQPYLQSTHVCQ
Protein Sequence KEDVIGIKEMKMPEGRKDEKKEGRKNVQDRPSEAEDTKSNRKSAMDLNDNNNVIVQSA
                 EKEKNEKTNQTNGAEVLQVTNTDDEMMPENHKENLNKNNNNNYVAVSYLNNCRQKTSI
                 LEFLDLLPLSSEANDTANEYEIEKLENTSRISELLGIFESEKTYSRNVLAMALKKQTD
                 RAAAGSPVQPAPKPSLSRGLMVKGGSSIISPDTNLLNIKGSHSKSKNLHFFFSNTVKI
                 TAFSKKNENIFNCDLIDSVDQIKNMPCLDLRELERMLNLGMLKQQKLPAIMKTQVLML

[0473] Further analysis of the NOV34a protein yielded the following properties shown in Table 34B.

TABLE 34B
Protein Sequence Properties NOV34a
PSort     0.6500 probability located in cytoplasm;
analysis: 0.1000 probability located in
          mitochondrial matrix space; 0.1000
          probability located in lysosome
          (lumen);
          0.0000 probability located in
          endoplasmic reticulum (membrane)
SignalP   No Known Signal Sequence Predicted
analysis:

[0474] 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.

TABLE 34C
Geneseq Results for NOV34a
		NOV34a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent #,	Match	the Matched	Expect
Identifier	Date]	Residues	Region	Value
AAE16626	Human 41441 protein encoded by	1 . . . 380	380/380 (100%)	0.0
	EST clone AW755252 DNA -	105 . . . 484	380/380 (100%)
	Homo sapiens, 547 aa.
	[WO200192567-A2, 06-DEC-2001]
AAU20632	Human secreted protein, Seq ID	1 . . . 380	379/380 (99%)	0.0
	No: 624 - Homo sapiens, 547 aa.	105 . . . 484	379/380 (99%)
	[WO200155326-A2, 02-AUG-2001]
AAU20575	Human secreted protein, Seq ID	1 . . . 380	379/380 (99%)	0.0
	No: 567 - Homo sapiens, 547 aa.	105 . . . 484	379/380 (99%)
	[WO200155326-A2, 02-AUG-2001]
ABG04347	Novel human diagnostic protein	1 . . . 65	65/65 (100%)	5e−32
	#4338 - Homo sapiens, 171 aa.	107 . . . 171	65/65 (100%)
	[WO200175067-A2, 11-OCT-2001]
ABG04347	Novel human diagnostic protein	1 . . . 65	65/65 (100%)	5e−32
	#4338 - Homo sapiens, 171 aa.	107 . . . 171	65/65 (100%)
	[WO200175067-A2, 11-OCT-2001]

[0475] In a BLAST search of public sequence datbases, the NOV34a protein was found to have homology to the proteins shown in the BLASTP data in Table 34D.

TABLE 34D
Public BLASTP Results for NOV34a
		NOV34a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9UHB6	Epithelial protein lost in	23 . . . 182	48/183 (26%)	3e−08
	neoplasm - Homo sapiens	513 . . . 692	83/183 (45%)
	(Human), 759 aa.
AAM08756	HYPOTHETICAL 83.2 KDA	16 . . . 336	74/353 (20%)	4e−05
	PROTEIN - Dictyostelium	336 . . . 670	137/353 (37%)
	discoideum (Slime mold), 734 aa.
O96245	MTN3/RAG1IP-LIKE PROTEIN -	106 . . . 234	34/132 (25%)	3e−04
	Plasmodium falciparum, 686 aa.	117 . . . 248	59/132 (43%)
Q9ERGO	Epithelial protein lost in	23 . . . 71	22/49 (44%)	3e−04
	neoplasm (mEPLIN) - Mus	511 . . . 557	30/49 (60%)
	musculus (Mouse), 753 aa.
P90523	PUTATIVE TRANSCRIPTION	123 . . . 349	46/228 (20%)	6e−04
	FACTOR - Dictyostelium	12 . . . 229	83/228 (36%)
	discoideum (Slime mold), 872 aa.

[0476] PFam analysis predicts that the NOV34a protein contains the domains shown in the Table 34E.

TABLE 34E
Domain Analysis of NOV34a
Pfam Domain	NOV34a	Identities/	Expect Value
	Match Region	Similarities
		for the
		Matched Region

Example 35

[0477] The NOV35 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 35A.

TABLE 35A
NOV35 Sequence Analysis
                 SEQ ID NO:75         1826 bp
NOV35a,          CGGCCGCGTCGACGGAAGGAACCTGACGACTTAGCAGGGTATCACTGGACAGGCCATG
CG148240-01      GCTCCACGGTCCCGGCGACGAAGGCACAAGAAACCTCCCTCATCAGTGGCTCCCATCA
DNA Sequence     TCATGGCCCCAACCACAATTGTGACCCCTGTGCCTCTGACCCCCTCAAAACCTGGCCC
                 TAGCATTGACACACTTGGCTTCTTCTCCTTGGATGATAATGTTCCTGGCCTATCGCAG
                 CTGATCCTTCAAAAGCTGAACATGAAAAGCTATGAAGAATATAAGTTGGTGGTAGATG
                 GGGGTACCCCCGTATCAGGCTTTGGATTTCGATGTCCTCAAGAAATGTTCCAGAGGAT
                 GGAAGACACATTTCGATTCTGTGCTCACTGTAGAGCACTCCCTAGTGGGCTTTCAGAC
                 TCCAAGGTTCTCCGGCACTGTAAGAGGTGCAGAAATGTCTATTACTGTGGTCCAGAGT
                 GCCAGAAGTCAGACTGGCCCGCACACAGGAGGGTTTGTCAAGAGCTTCGTCTTGTGGC
                 TGTGGACCGTCTCATGGAATGGCTTCTGGTCACAGGTGATTTTGTTCTACCCTCAGGA
                 CCTTGGCCATGGCCACCTGAAGCTGTACAGGACTGGGACTCCTGGTTTTCTATGAAGG
                 GGTTACACCTAGATGCTACATTGGATGCTGTGCTAGTTAGTCATGCTGTGACCACCTT
                 ATGGGCCAGTGTAGGACGGCCAAGGCCAGACCCGGATGTCCTGCAGGGATCTTTGAAG
                 CGGCTGCTGACAGATGTCCTGTCACGGCCCTTGACTCTAGGCCTAGGACTTAGGGCCT
                 TGGGGATAGATGTTAGGAGGACTGGGGGAAGCACAGTGCATGTGGTTGGTGCTTCCCA
                 TGTGGAGACATTTCTTACTCGCCCAGGGGACTATGATGAGCTTGGTTACATGTTTCCT
                 GGGCACCTTGGACTCCGTGTGGTCATGGTGGGTGTAGATGTAGCTACTGGCTTTTCAC
                 AGAGCACCTCAACTTCACCCCTGGAACCTGGCACAATTCAGCTTAGTGCCCACAGGGG
                 CCTCTACCATGACTTCTGGGAGGAGCAAGTAGAGACCGGGCAGACACACCATCCAGAT
                 TTGGTGGCGGCATTCCATCCAGGTTTTCATTCCTCCCCAGACTTGATGGAGGCTTGGC
                 TGCCCACCCTGCTGCTACTTCGTGACTATAAGATTCCTACATTGATTACTGTTTACAG
                 CCATCAGGAGTTGGTATCCTCTTTGCAGATTCTGGTGGAACTGGATACACACATCACT
                 GCCTTTGGGTCTAATCCTTTCATGTCCCTCAAACCTGAACAGGTCTATTCCAGTCCCA
                 ACAAGCAGCCAGTATACTGCAGTGCATACTATATCATGTTTCTTGGAAGCTCCTGTCA
                 GCTGGATAATAGGCAATTAGAAGAGAAAGTGGACGGCGGGATTTAAATAGATCATAAC
                 TGGACATCTGGAAAACGGGGAGTTTGTGATGAAATTACCCTGCTAATGCCAGGTTCTT
                 GCAAACTTTGAAAAACATTATATTCTAAACCTCATTTACTGTTTGGGTAAAAATTCTA
                 AGCTGAATGAGAGTTTCTGTATAACATAACTGGTTTCTTTCTTTTTTTGAGATGGAGT
                 CTTGCTCTGTTGCCCAGGCTGGAGTGCAGCGGCATGATCTCGACTCACTGCAGCCTCC
                 GCCTCCTGGGTTCAAGTGGTTCTCCTGCCTCAGCCTCCCTAGTAGCTGGGATTACAGG
                 TGCACACCACCACACCTGGCTAATTTTTGTATTTTTAGCAGACAGGGTTTCACCATGT
                 TGGCCAGGCTCGTATCAAACCCTTGACC
                 ORF Start: ATG at 56 ORF Stop: TAA at 1436
                 SEQ ID NO:76         460 aa MW at 51288.3 kD
NOV35a,          MAPRSRRRRHKKPPSSVAPIIMAPTTIVTPVPLTPSKPGPSIDTLGFFSLDDNVPGLS
CG148240-01      QLILQKLNMKSYEEYKLVVDGGTPVSGFGFRCPQEMFQRMEDTFRFCAHCRALPSGLS
Protein Sequence DSKVLRHCKRCRNVYYCGPECQKSDWPAHRRVCQELRLVAVDRLNEWLLVTGDFVLPS
                 GPWPWPPEAVQDWDSWFSMKGLHLDATLDAVLVSHAVTTLWASVGRPRPDPDVLQGSL
                 KRLLTDVLSRPLTLGLGLRALGIDVRRTGGSTVHVVGASHVETFLTRPGDYDELGYMF
                 PGHLGLRVVMVGVDVATGFSQSTSTSPLEPGTIQLSAHRGLYEDFWEEQVETGQTHHP
                 DLVAAFHPGFHSSPDLMEAWLPTLLLLRDYKIPTLITVYSHQELVSSLQILVELDTHI
                 TAFGSNPFMSLKPEQVYSSPNKQPVYCSAYYIMFLGSSCQLDNRQLEEKVDGGI

[0478] Further analysis of the NOV35a protein yielded the following properties shown in Table 35B.

TABLE 35B
Protein Sequence Properties NOV35a
PSort     0.5500 probability located in endoplasmic
analysis: reticulum (membrane); 0.2832
          probability located in lysosome (lumen);
          0.2287 probability located in
          microbody (peroxisome); 0.1000
          probability located in endoplasmic
          reticulum (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0479] 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 35C.

TABLE 35C
Geneseq Results for NOV35a
		NOV35a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent #,	Match	the Matched	Expect
Identifier	Date]	Residues	Region	Value
AAU21785	Novel human neoplastic disease	88 . . . 152	22/66 (33%)	6e−05
	associated polypeptide #218 - Homo	29 . . . 88	30/66 (45%)
	sapiens, 246 aa. [WO200155163-A1,
	02 Aug. 2001]
AAB74604	Human hBop-m protein sequence	88 . . . 152	22/66 (33%)	6e−05
	SEQ ID NO: 7 - Homo sapiens, 433	34 . . . 93	30/66 (45%)
	aa. [CN1272540-A, 08 Nov. 2000]
ABB03929	Human musculoskeletal system	88 . . . 152	22/66 (33%)	6e−05
	related polypeptide SEQ ID NO 1876 -	29 . . . 88	30/66 (45%)
	Homo sapiens, 246 aa.
	[WO200155367-A1, 02 Aug. 2001]
AAB21035	Human nucleic acid-binding protein,	88 . . . 152	22/66 (33%)	6e−05
	NuABP-39 - Homo sapiens, 433 aa.	34 . . . 93	30/66 (45%)
	[WO200044900-A2, 03 Aug. 2000]
AAB42760	Human ORFX ORF2524 polypeptide	88 . . . 152	22/66 (33%)	6e−05
	sequence SEQ ID NO: 5048 - Homo	30 . . . 89	30/66 (45%)
	sapiens, 429 aa. [WO200058473-A2,
	05 Oct. 2000]

[0480] In a BLAST search of public sequence datbases, the NOV35a protein was found to have homology to the proteins shown in the BLASTP data in Table 35D.

TABLE 35D
Public BLASTP Results for NOV35a
		NOV35a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9D5Z5	4833444M15RIK PROTEIN -	1 . . . 444	353/444 (79%)	0.0
	Mus musculus (Mouse), 446 aa.	1 . . . 443	392/444 (87%)
Q9NRG4	HSKM-B - Homo sapiens	88 . . . 152	22/66 (33%)	1e−04
	(Human), 433 aa.	34 . . . 93	30/66 (45%)
AAH23119	SIMILAR TO HSKM-B	105 . . . 152	20/48 (41%)	4e−04
	PROTEIN - Mus musculus	52 . . . 93	24/48 (49%)
	(Mouse), 433 aa.
Q9VU41	CG11253 PROTEIN - Drosophila	100 . . . 149	20/50 (40%)	5e−04
	melanogaster (Fruit fly), 451 aa.	407 . . . 448	26/50 (52%)
Q96E35	SIMILAR TO RIKEN CDNA	124 . . . 151	15/28 (53%)	0.001
	2700064H14 GENE - Homo	187 . . . 214	21/28 (74)
	sapiens (Human), 227 aa.

[0481] PFam analysis predicts that the NOV35a protein contains the domains shown in the Table 35E.

TABLE 35E
Domain Analysis of NOV35a
	NOV35a	Identities/
Pfam	Match	Similarities	Expect
Domain	Region	for the Matched Region	Value
zf-MYND	105 . . . 149	19/47 (40%)	2.5e−09
		34/47 (72%)

Example 36

[0482] The NOV36 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 36A.

TABLE 36A
NOV36 Sequence Analysis
                 SEQ ID NO:77        1130 bp
NOV36a,          ATGTGTACAAACCCTGAAATTAAACAAGAAGACCCCACAAATGTGGGGCCTGAATGAA
CG59975-01       AGCAACAAGTAACCATGGTTTCAGACACTGAAATCTTAAAGGTAGCTAGAACACATCA
DNA sequence     CGTCCAAGCAGAAAGCTACCTGGTGTACAACATCATGAGCAGTGGAGAGATTGAATGC
                 AGCAACACCCTAGAAGATGAGCTTGACCAGGCCTTACCCAGCCAGGCCTTCATTTACC
                 GTCCCATTCGACAGCGGGTCTACTCACTCTTACTGGAGGACTGTCAAGATGTCACCAG
                 CACCTGCCTAGCTGTCAAGGAGTGGTTTGTGTATCCTGGGAACCCACTGAGGCACCCG
                 GACCTCGTCAGGCCGCTGCAGATGACCATTCCAGGGGGAACGCCTAGTTTGAAAATAT
                 TATGGCTGAACCAAGAGCCAGAAATACAGGTTCGGCGCTTGGACACACTCCTAGCCTG
                 TTTCAATCTTTCCTCCTCAAGAGAAGAGCTGCAGGCTGTCGAAAGCCCATTTCAAGCT
                 TTGTGCTGCCTCTTGATCTACCTCTTTGTCCAGGTGGACACGCTTTGCCTGGAGGATT
                 TGCATGCGTTTATTGCGCAGGCCTTGTGCCTCCAAGGAAAATCCACCTCGCAGCTTGT
                 AAATCTACAGCCTGATTACATCAACCCCAGAGCCGTGCAGCTGGGCTCCCTTCTCGTC
                 CGCGGCCTCACCACTCTGGTTTTAGTCAACAGCGCATGTGGCTTCCCCTGGAAGACGA
                 GTGATTTCATGCCCTGGAATGTATTTGACGGGAAGCTTTTTCATCAGAAGTACTTGCA
                 ATCTGAAAAGGGTTATGCTGTGGAGGTTCTTTTAGAACAAAATAGATCTCGGCTCACC
                 AAATTCCACAACCTGAAGGCAGTCGTCTGCAAGGCCTGCATGAAGGAGAACAGACGCA
                 TCACTGGCCGAGCCCACTGGGGCTCACACCACGCAGGGAGGTGGGGAAGACAGGGCTC
                 CAGCTACCACAGGACGGGCTCTGGGTATAGCCGTTCCAGTCAGGGACAGCCGTGGAGA
                 GACCAGGGACCAGGAAGCAGACAGTATGAGCATGACCAGTGGAGAAGGTACTAGTCAA
                 CCTCCAGGTAAGTTCATCACCTGCATCT
                 ORF Start: ATG at 1 ORF Stop: TAG at 1096
                 SEQ ID NO:78        365 aa MW at 41672.1 kD
NOV36a,          MCTNPEIKQEDPTNVGPEVKQQVTMVSDTEILKVARTHHVQAESYLVYNIMSSGEIEC
CG59975-01       SNTLEDELDQALPSQAFIYRPIRQRVYSLLLEDCQDVTSTCLAVKEWFVYPGNPLRHP
Protein Sequence DLVRPLQMTIPGGTPSLKILWLNQEPEIQVRRLDTLLACFNLSSSREELQAVESPFQA
                 LCCLLIYLFVQVDTLCLEDLHAFIAQALCLQGKSTSQLVNLQPDYINPRAVQLGSLLV
                 RGLTTLVLVNSACGFPWKTSDFMPWNVFDGKLFHQKYLQSEKGYAVEVLLEQNRSRLT
                 KFHNLKAVVCKACMKENRRITGRAHWGSHHAGRWGRQGSSYHRTGSGYSRSSQGQPWR
                 DQGPGSRQYEHDQWRRY
                 SEQ ID NO:79        1124 bp
NOV36b,          TTATGTGTACAAACCCTGAAATTAAACAAGAAGACCCCACAAATGTGGGGCCTGAAGT
CG59975-02       AAAGCAACAAGTAACCATGGTTTCAGACACTGAAATCTTAAAGGTTGCTAGAACACAT
DNA Sequence     CACGTCCAAGCAGAAAGCTACCTGGTGTACAACATCATGAGCAGTGGAGAGATTGAAT
                 GCAGCAACACCCTAGAAGATGAGCTTGACCAGGCCTTACCCAGCCAGGCCTTCATTTA
                 CCGTCCCATTCGACAGCGGGTCTACTCACTCTTACTGGAGGACTGTCAAGATGTCACC
                 AGCACCTGCCTAGCTGTCAAGGAGTGGTTTGTGTATCCTGGGAACCCACTGAGGCACC
                 CGGACCTCGTCAGGCCGCTGCAGATGACCATTCCAGGGGGAACGCCTAGTTTGAAAAT
                 ATTATGGCTGAACCAAGAGCCAGAAATACAGGTTCGGCGCTTGGACACACTCCTAGCC
                 TGTTTCAATCTTTCCTCCTCAAGAGAAGAGCTGCAGGCTGTCGAAAGCCCATTTCAAG
                 CTTTGTGCTGCCTCTTGATCTACCTCTTTGTCCAGGTGGACACGCTTTGCCTGGAGGA
                 TTTGCATGCGTTTATTGCGCAGGCCTTGTGCCTCCAAGGAAAATCCACCTCGCAGCTT
                 GTAAATCTACAGCCTGATTACATCAACCCCAGAGCCGTGCAGCTGGGCTCCCTTCTCG
                 TCCGCGGCCTCACCACTCTGGTTTTAGTCAACAGCGCATGTGGCTTCCCCTGGAAGAC
                 GAGTGATTTCATGCCCTGGAATGTATTTGACGGGAAGCTTTTTCATCAGAAGTACTTG
                 CAATCTGAAAAGGGTTATGCTGTGGAGGTTCTTTTAGAACAAAATAGATCTCGGCTCA
                 CCAAATTCCACAACCTGAAGGCAGTCGTCTGCAAGGCCTGCATGAAGGAGAACAGACG
                 CATCACTGGCCGAGCCCACTGGGGCTCACACCACGCAGGGAGGTGGGGAAGACAGGGC
                 TCCAGCTACCACAGGACGGGCTCTGGGTATAGCCGTTCCAGTCAGGGACAGCCGTGGA
                 GAGACCAAGGACCAGGAAGCAGACAGTATGAGCATGACCAGTGGAGAAGGTACTAGTC
                 AACCTCCAGGTAAGTTCATCAC
                 ORF Start: ATG at 3 ORF Stop: TAG at 1098
                 SEQ ID NO:80        365 aa MW at 41672.1 kD
NOV36b,          MCTNPEIKQEDPTNVGPEVKQQVTMVSDTEILKVARTHHVQAESYLVYNIMSSGEIEC
CG59975-02       SNTLEDELDQALPSQAFIYRPIRQRVYSLLLEDCQDVTSTCLAVKEWFVYPGNPLRHP
Protein Sequence DLVRPLQMTIPGGTPSLKILWLNQEPEIQVRRLDTLLACFNLSSSREELQAVESPFQA
                 LCCLLIYLFVQVDTLCLEDLHAFIAQALCLQGKSTSQLVNLQPDYINPRAVQLGSLLV
                 RGLTTLVLVNSACGFPWKTSDFMPWNVFDGKLFHQKYLQSEKGYAVEVLLEQNRSRLT
                 KFHNLKAVVCKACMKENRRITGRAHWGSHHAGRWGRQGSSYHRTGSGYSRSSQGQPWR
                 DQGPGSRQYEHDQWRRY

[0483] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 36B.

TABLE 36B
Comparison of NOV36a against NOV36b.
Protein	NOV36a Residues/	Identities/
Sequence	Match Residues	Similarities for the Matched Region
NOV36b	1 . . . 365	350/365 (95%)
	1 . . . 365	350/365 (95%)

[0484] Further analysis of the NOV36a protein yielded the following properties shown in Table 36C.

TABLE 36C
Protein Sequence Properties NOV36a
PSort     0.8500 probability located in endoplasmic reticulum
analysis: (membrane); 0.4400 probability located in plasma
          membrane; 0.3044 probability located in microbody
          (peroxisome); 0.1000 probability located in
          mitochondrial inner membrane
SignalP   No Known Signal Sequence Predicted
analysis:

[0485] 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.

TABLE 36D
Geneseq Results for NOV36a
		NOV36a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAU19923	Novel human calcium-binding	1 . . . 365	331/365 (90%)	0.0
	protein #32 - Homo sapiens, 486	156 . . . 486	331/365 (90%)
	aa. [WO200155304-A2, 02 Aug.
	2001]
AAW85612	Secreted protein clone fh123_5 -	1 . . . 285	285/285 (100%)	e−166
	Homo sapiens, 916 aa.	546 . . . 830	285/285 (100%)
	[WO9849302-A1, 05 Nov. 1998]
ABB12073	Human secreted protein	1 . . . 281	281/281 (100%)	e−164
	homologue, SEQ ID NO: 2443 -	578 . . . 858	281/281 (100%)
	Homo sapiens, 915 aa.
	[WO200157188-A2, 09 Aug.
	2001]
AAY53673	Protein 405_hum sequence used	30 . . . 274	87/266 (32%)	1e−30
	for clustral X alignment - Rattus	554 . . . 816	134/266 (49%)
	sp, 1118 aa. [WO9960164-A1,
	25 Nov. 1999]
AAY53670	Mechanical stress induced protein	30 . . . 274	87/266 (32%)	1e−30
	405 amino acid sequence - Rattus	554 . . . 816	134/266 (49%)
	sp, 1118 aa. [WO9960164-A1,
	25 Nov. 1999]

[0486] In a BLAST search of public sequence datbases, the NOV36a protein was found to have homology to the proteins shown in the BLASTP data in Table 36E.

TABLE 36E
Public BLASTP Results for NOV36a
		NOV36a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q96EK7	UNKNOWN (PROTEIN FOR	1 . . . 365	365/365 (100%)	0.0
	MGC: 20434) - Homo sapiens	546 . . . 910	365/365 (100%)
	(Human), 910 aa.
Q96JI9	KIAA1838 PROTEIN - Homo	1 . . . 365	365/365 (100%)	0.0
	sapiens (Human), 917 aa	553 . . . 917	365/365 (100%)
	(fragment).
Q9N061	UNNAMED PROTEIN	1 . . . 365	356/365 (97%)	0.0
	PRODUCT - Macaca fascicularis	1 . . . 365	361/365 (98%)
	(Crab eating macaque)
	(Cynomolgus monkey), 365 aa.
Q99LL4	RIKEN CDNA 4932442K08	1 . . . 365	294/365 (80%)	e−170
	GENE - Mus musculus (Mouse),	1 . . . 362	321/365 (87%)
	362 aa.
Q9D4F4	4932442K08RIK PROTEIN - Mus	1 . . . 365	293/365 (80%)	e−170
	musculus (Mouse), 362 aa.	1 . . . 362	321/365 (87%)

[0487] PFam analysis predicts that the NOV36a protein contains the domains shown in the Table 36F.

TABLE 36F
Domain Analysis of NOV36a
	Pfam	NOV36a	Identities/	Expect
	Domain	Match	Similarities	Value
		Region	for the Matched Region

Example 37

[0488] The NOV37 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 37A.

TABLE 37A
NOV37 Sequence Analysis
                 SEQ ID NO:81         1173 bp
NOV37a,          GCATACTATTACATTACAGCTTATAATGGCAACCCCTGAAGAAAACAGCAATCCCCAT
CG89947-01       GACAGAGCAACACCCCAGCTGCCAGCACAGCTGCAGGAGCTTGAGCATCGGGTGGCCC
DNA Sequence     GGAGACGGCTGTCCCAGGCCCGCCACCGAGCCACCCTGGCAGCGCTCTTCAACAACCT
                 CAGGAAGACAGTGTACTCTCAGTCTGATCTCATAGCCTCAAAGTGGCAGGTTCTGAAT
                 AAGGCAAAGAGTCATATTCCAGAACTGGAGCAAACCCTGGATAATTTGCTGAAGCTGA
                 AAGCATCCTTCAACCTGGAAGATGGGCATGCAAGCAGCTTAGAGGAGGTCAAGAAAGA
                 ATATGCCAGCATGTATTCTGGAAATGACAGCCTGCTTTCAAACAGTTTTCCTCAGAAT
                 GGTTCCTCCCCTTGGTGCCCAACTGAGGCAGTCAGGAAGGATGCTGAGGAGGAGGAAG
                 ATGAGGAAGAGGAAGATCAAGAAGAAGAGGAGGAGGAAGAAGAAGAGGAGGAGGAGGA
                 GGAAGAGGAGGAAGAGGAAGAGGAGGAGGAGGAAGAGGAGAAAAAAGTGATCTTATAC
                 TCCCCAGGAACTTTGTCGCCTGACCTCATGGAATTTGAACGGTATCTCAACTTTTACA
                 AACAGACGATGGACCTTCTGACTGGCAGCGGGATCATTACCCCGCAGGAGGCGGCGCT
                 GCCCATCGTCTCCGCGGCCATCTCCCACCTGTGGCAGAACCTCTCGGAGGAGAGGAAG
                 GCCAGCCTCCGGCAGGCCTGGGCGCAGAAGCACCGCGGCCCTGCGACCCTGGCGGAGG
                 CCTGCCGAGAGCCGGCCTGTGCCGAGGGCAGCGTGAAGGACAGCGGCGTGGACAGCCA
                 GGGGGCCAGCTGCTCGCTGGTCTCCACGCCCGAGGAGATCCTTTTTGAGGATGCCTTT
                 GATGTGGCAAGCTTCCTGGACAAAAGTGAGGTTCCGAGTACATCTAGCTCCAGTTCAG
                 TGCTTGCCAGCTGCAACCCAGAAAACCCAGAGGAGAAGTTTCAGCTCTATATGCAGAT
                 CATCAACTTTTTTAAAGGCCTTAGCTGTGCAAACACTCAAGTAAAGCAGGAAGCATCC
                 TTTCCCGTTGATGAAGAGATGATCATGTTGCAGTGCACAGAGACCTTTGACGATGAAG
                 ATTTGTAATGCAG
                 ORF Start: ATG at 26 ORF Stop: TAA at 1166
                 SEQ ID NO: 82        380 aa MW at 42845.4 kD
NOV37a,          MATPEENSNPHDRATPQLPAQLQELEHRVARRRLSQARHRATLAALFNNLRKTVYSQS
CG89947-01       DLIASKWQVLNKAKSHIPELEQTLDNLLKLKASFNLEDGHASSLEEVKKEYASMYSGN
Protein Sequence DSLLSNSFPQNGSSPWCPTEAVRKDAEEEEDEEEEDQEEEEEEEEEEEEEEEEEEEEE
                 EEEEEKKVILYSPGTLSPDLMEFERYLNFYKQTMDLLTGSGIITPQEAALPIVSAAIS
                 HLWQNLSEERKASLRQAWAQKHRGPATLAEACREPACAEGSVKDSGVDSQGASCSLVS
                 TPEEILFEDAFDVASFLDKSEVPSTSSSSSVLASCNPENPEEKFQLYMQIINFFKGLS
                 CANTQVKQEASFPVDEEMIMLQCTETFDDEDL
                 SEQ ID NO:83         1178 bp
NOV37b,          ATGGCAACCCCTAAAGAAAACAGCAATCCCCATGACAGAGCAACACCCCAGCTGCCAG
CG89947-02       CACAGCTGCAGGAGCTTGAGCATCGGGTGGCCCGGAGACGGCTGTCCCAGGCCCGCCA
DNA Sequence     CCGAGCCACCCTGGCAGCACTCTTCAACAACCTCAGGAAGACAGTGTACTCTCAGTCT
                 GATCTCATAGCCTCAAAGTGGCAGGTTCTGAATAAGGCAAAGAGTCATATTCCAGAAC
                 TGGAGCAAACCCTGGATAATTTGCTGAAGCTGAAAGCATCCTTCAACCTGGAAGATGG
                 GCATGCAAGCAGCTTAGAGGAGGTCAAGAAAGAATATGCCAGCATGTATTCTGGAAAT
                 GACAGCCTGCTTTCAAACAGTTTTCCTCAGAATGGTTCCTCCCCTTGGTGCCCAACTG
                 AGGCAGTCAGGAAGGATGCTGAGGAGGAGGAAGATGAGGAAGAGGAAGATCAAGAAGA
                 AGAGGAGGAGGAAGAAGAAGAGGAGGAGGAGGAGGAAGAGGAGGAAGAGGAAGAGGAG
                 GAGGAGGAAGAGGAGAAAAAAGTGATCTTATACTCCCCAGGAACTTTGTCGCCTGGCC
                 TCATGGAATTTGAACGGTATCTCAACTTTTACAAACAGACGATGGACCTTCTGACTGG
                 CAGCGGGATCATTACCCCGCAGGAGGCGGCGCTGCCCATCGTCTCCGCGGCCATCTCC
                 CACCTGTGGCAGAACCTCTCGGAGGAGAGGAAGGCCAGCCTCCGGCAGGCCTGGGCGC
                 AGAAGCACCGCGGCCCTGCGACCCTGGCGGAGGCCTGCCGAGAGCCGGCCTGTGCCGA
                 GGGCAGCGTGAAGGACAGCGGCGTGGACAGCCAGGGGGCCAGCTGCTCGCTGGTCTCC
                 ACGCCCGAGGAGATCCTTTTTGAGGATGCCTTTGATGTGGCAAGCTTCCTGGACAAAA
                 GTGAGGTTCCGAGTACATCTAGCTCCAGTTCAGTGCTTGCCAGCTGCAACCCAGAAAA
                 CCCAGAGGAGAAGTTTCAGCTCTATATGCAGATCATCAACTTTTTTAAAGGCCTTAGC
                 TGTGCAAACACTCAAGTAAAGCAGGAAGCATCCTTTCCCGTTGATGAAGAGATGATCA
                 TGTTGCAGTGTACAGAGACCTTTGACGATGAAGATTTGTAATGCCAGGGTTTGCTGTT
                 TTCTTAAGGGGTTGCCAT
                 ORF Start: ATG at 1  ORF Stop: TAA at 1141
                 SEQ ID NO:84         380 aa MW at 42786.4 kD
NOV37b,          MATPKENSNPHDRATPQLPAQLQELEHRVARRRLSQARHRATLAALFNNLRKTVYSQS
CG89947-02       DLIASKWQVLNKAKSHIPELEQTLDNLLKLKASFNLEDGHASSLEEVKKEYASMYSGN
Protein Sequence DSLLSNSFPQNGSSPWCPTEAVRKDAEEEEDEEEEDQEEEEEEEEEEEEEEEEEEEEE
                 EEEEEKKVILYSPGTLSPGLMEPERYLNFYKQTMDLLTGSGIITPQEAALPIVSAAIS
                 TPEEILFEDAFDVASFLDKSEVPSTSSSSSVLASCNPENPEEKFQLYMQIINFFKGLS
                 CANTQVKQEASFPVDEEMIMLQCTETFDDEDL

[0489] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 37B.

TABLE 37B
Comparison of NOV37a against NOV37b.
Protein	NOV37a Residues/	Identities/
Sequence	Match Residues	Similarities for the Matched Region
NOV37b	1 . . . 380	326/380 (85%)
	1 . . . 380	327/380 (85%)

[0490] Further analysis of the NOV37a protein yielded the following properties shown in Table 37C.

TABLE 37C
Protein Sequence Properties NOV37a
Psort     0.4500 probability located in cytoplasm; 0.3000 probability located in
analysis: microbody (peroxisome); 0.1000 probability located in mitochondrial matrix
          space; 0.1000 probability located in lysosome (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0491] 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 37D.

TABLE 37D
Geneseq Results for NOV37a
			Identities/
		NOV37a	Similarities
		Residues/	for the
Geneseq	Protein/Organism/Length [Patent	Match	Matched	Expect
Identifier	#, Date]	Residues	Region	Value
ABG11278	Novel human diagnostic protein	124 . . . 179	39/56 (69%)	2e−14
	#11269 - Homo sapiens, 62 aa.	6 . . . 61	45/56 (79%)
	[WO200175067-A2, 11-OCT-2001]
ABG11278	Novel human diagnostic protein	124 . . . 179	39/56 (69%)	2e−14
	#11269 - Homo sapiens, 62 aa.	6 . . . 61	45/56 (79%)
	[WO200175067-A2, 11-OCT-2001]
ABG06956	Novel human diagnostic protein	143 . . . 193	35/51 (68%)	3e−12
	#6947 - Homo sapiens, 58 aa.	4 . . . 54	41/51 (79%)
	[WO200175067-A2, 11-OCT-2001]
ABG04384	Novel human diagnostic protein	143 . . . 193	35/51 (68%)	3e−12
	#4375 - Homo sapiens, 58 aa.	4 . . . 54	41/51 (79%)
	[WO200175067-A2, 11-OCT-2001]
ABG06956	Novel human diagnostic protein	143 . . . 193	35/51 (68%)	3e−12
	#6947 - Homo sapiens, 58 aa.	4 . . . 54	41/51 (79%)
	[WO200175067-A2, 11-OCT-2001]

[0492] In a BLAST search of public sequence datbases, the NOV37a protein was found to have homology to the proteins shown in the BLASTP data in Table 37E.

TABLE 37E
Public BLASTP Results for NOV37a
		NOV37a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
P70278	STRA8 PROTEIN - Mus musculus	1 . . . 377	262/392 (66%)	e−138
	(Mouse), 393 aa.	1 . . . 392	295/392 (74%)
AAL92605	HYPOTHETICAL 96.2 KDA	52 . . . 179	51/128 (39%)	5e−13
	PROTEIN - Dictyostelium	710 . . . 796	71/128 (54%)
	discoideum (Slime mold), 806 aa.
BAB90435	OSJNBB0006H05.12 PROTEIN -	83 . . . 180	37/98 (37%)	7e−10
	Oryza sativa (japonica cultivar-	49 . . . 146	54/98 (54%)
	group), 157 aa.
Q96MU7	CDNA FLJ31868 FIS, CLONE	70 . . . 181	45/112 (40%)	2e−09
	NT2RP7001962, HIGHLY	92 . . . 195	66/112 (58%)
	SIMILAR TO RATTUS
	NORVEGICUS YT521 RNA
	SPLICING-RELATED PROTEIN -
	Homo sapiens (Human), 658 aa.
O35788	CYCLIC NUCLEOTIDE-GATED	103 . . . 181	30/79 (37%)	1e−08
	CHANNEL BETA SUBUNIT -	398 . . . 476	51/79 (63%)
	Rattus norvegicus (Rat), 1339 aa.

[0493] PFam analysis predicts that the NOV37a protein contains the domains shown in the Table 37F.

TABLE 37F
Domain Analysis of NOV37a
		Identities/
		Similarities
	NOV37a	for the
Pfam Domain	Match Region	Matched Region	Expect Value
HLH	31 . . . 79	16/57 (28%)	0.17
		32/57 (56%)

Example 38

[0494] The NOV38 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 38A.

TABLE 38A
NOV38 Sequence Analysis
                SEQ ID NO:85        2490 bp
NOV38a,         ATGTTTCACCTGAAGGACGCTGAAATGGGAGCCTTTACCTTCTTTGCCTCGGCTCTGC
CG03366-02      CACATGATGTTTGTGGAAGCAATGGACTTCCTCTCACACCAAATTCCATCAAAATTTT
DNA Sequence    AGGGCGCTTTCAAATCCTTAAAACCATCACCCATCCCAGACTCTGCCAGTATGTGGAT
                ATTTCTAGGGGAAAGCATGAACGACTAGTGGTCGTGGCTGAACATTGTGAACGTAGTC
                TGGAAGACTTGCTTCGAGAAAGGAAACCTGTGAGGTATCCCTCGTACTTGGCCCCTGA
                GGTAATTGCACAGGGAATTTTCAAAACCACTGATCACATGCCAAGTAAAAAACCATTG
                CCTTCTGGCCCCAAATCAGATGTATGGTCTCTTGGAATCATTTTATTTGAGCTTTGTG
                TGGGAAGAAAATTATTTCAGAGCTTGGATATTTCTGAAAGACTAAAATTTTTGCTTAC
                TTTGGATTGTGTAGATGACACTTTAATAGTTCTGGCTGAAGAGCATGGGTGTTTGGAC
                ATTATAAAGGAGCTTCCTGAAACTGTGATAGATCTTTTGAATAAGTGCCTTACCTTCC
                ATCCTTCTAAGAGGCCAACCCCAGATGAATTAATGAAGGACAAAGTATTCAGTGAGGT
                ATCACCTTTATATACCCCCTTTACCAAACCTGCCAGTCTGTTTTCATCTTCTCTGAGA
                TGTGCTGATTTAACTCTGCCTGAGGATATCAGTCAGTTGTGTAAAGATATAAATAATG
                ATTACCTGGCAGAAAGATCTATTGAAGAAGTGTATTACCTTTGGTGTTTGGCTGGAGG
                TGACTTGGAGAAAGAGCTTGTCAACAAGGAAATCATTCGATCCAAACCACCTATCTGC
                ACACTCCCCAATTTTCTCTTTGAGGATGGTGAAAGCTTTGGACAAGGTCGAGATAGAA
                GCTCGCTTTTAGATGATACCACTGTGACATTGTCGTTATGCCAGCTAAGAAATAGATT
                GAAAGATGTTGGTGGAGAAGCATTTTACCCATTACTTGAAGATGACCAGTCTAATTTA
                CCTCATTCAAACAGCAATAATGAGTTGTCTGCAGCTGCCATGCTCCCTTTAATCATCA
                GAGAGAAGGATACAGAGTACCAACTAAATAGAATTATTCTCTTCGACAGGCTAAAGGC
                TTATCCATATAAAAAAAACCAAATCTGGAAAGAAGCAAGAGTTGACATTCCTCCTCTT
                ATGAGAGGTTTAACCTGGGCTGCTCTTCTGGGAGTTGAGGGAGCTATTCATGCCAAGT
                ACGATGCAATTGATAAAGACACTCCAATTCCTACAGATAGACAAATTGAAGTGGATAT
                TCCTCGCTGTCATCAGTACGATGAACTGTTATCATCACCAGAAGGTCATGCAAAATTT
                AGGCGTGTATTAAAAGCCTGGGTAGTGTCTCATCCTGATCTTGTGTATTGGCAAGGTC
                TTGACTCACTTTGTGCTCCATTCCTATATCTAAACTTCAATAATGAAGCCTTGGCTTA
                TGCATGTATGTCTGCTTTTATTCCCAAATACCTGTATAACTTCTTCTTAAAAGACAAC
                TCACATGTAATACAAGAGTATCTGACTGTCTTCTCTCAGATGATTGCATTTCATGATC
                CAGAGCTGAGTAATCATCTCAATCAGATTGGCTTCATTCCAGATCTCTATGCCATCCC
                TTGGTTTCTTACCATGTTTACTCATGTATTTCCACTACACAAAATTTTCCACCTCTGG
                GATACCTTACTACTTGGGAATTCCTCTTTCCCATTCTGTATTGGAGTAGCAATTCTTC
                AGCAGCTGCGGGACCGGCTTTTGGCTAATGGCTTTAATGAGTGTATTCTTCTCTTCTC
                CGATTTACCAGAAATTGACATTGAACGCTGTGTGAGAGAATCTATCAACCTGTTTTGT
                TGGACTCCTAAAAGTGCTACTTACAGACAGCATGCTCAACCTCCAAAGCCATCTTCTG
                ACAGCAGTGGAGGCAGAAGTTCGGCACCTTATTTCTCTGCTGAGTGTCCAGATCCTCC
                AAAGACAGATCTGTCAAGAGAATCCATCCCATTAAATGACCTGAAGTCAGAAGTATCA
                CCACGGATTTCAGCAGAGGACCTGATTGACTTGTGTGAGCTCACAGTGACAGGCCACT
                TCAAAACACCCAGCAAGAAAACAAAGTCCAGTAAACCAAAGCTCCTGGTGGTTGACAT
                CCTGAATAGTGAAGACTTTATTCGTGGTCACATTTCAGGAAGCATCAACATTCCATTC
                AGTGCTGCCTTCACTGCAGAAGGGGAGCTTACCCAGGGCCCTTACACTGCTATGCTCC
                AGAACTTCAAAGGGAAGGTCATTGTCATCGTGGGGCATGTGGCAAAACACACAGCTGA
                GTTTGCAGCTCACCTTGTGAAGATGAAATATCCAAGAATCTGTATTCTAGATGGTGGC
                ATTAATAAAATAAAGCCAACAGGCCTCCTCACCATCCCATCTCCTCAAATATGA
                ORF Start: ATG at 1 ORF Stop: TGA at 2488
                SEQ ID NO: 86       829 aa MW at 93637.7 kD
NOV38a,         MFHLKDAEMGAFTFFASALPHDVCGSNGLPLTPNSIKILGRFQILKTITHPRLCQYVD
CG93366-02      ISRGKHERLVVVAEHCERSLEDLLRERKPVRYPSYLAPEVIAQGIFKTTDHMPSKKPL
Protein Sequnce PSGPKSDVWSLGIILFELCVGRKLFQSLDISERLKFLLTLDCVDDTLIVLAEEHGCLD
                IIKELPETVIDLLNKCLTFHPSKRPTPDELMKDKVFSEVSPLYTPFTKPASLFSSSLR
                CADLTLPEDISQLCKDINNDYLAERSIEEVYYLWCLAGGDLEKELVNKEIIRSKPPIC
                TLPNFLFEDGESFGQGRDRSSLLDDTTVTLSLCQLRNRLKDVGGEAFYPLLEDDQSNL
                PHSNSNNELSAAAMLPLIIREKDTEYQLNRIILFDRLKAYPYKKNQIWKEARVDIPPL
                MRGLTWAALLGVEGAIHAKYDAIDKDTPIPTDRQIEVDIPRCHQYDELLSSPEGHAKF
                RRVLKAWVVSHPDLVYWQGLDSLCAPFLYLNFNNEALAYACMSAFIPKYLYNFFLKDN
                SHVIQEYLTVFSQMIAFHDPELSNHLNQIGFIPDLYAIPWFLTMFTHVFPLHKIFHLW
                DTLLLGNSSFPFCIGVAILQQLRDRLLANGFNECILLFSDLPEIDIERCVRESINLFC
                WTPKSATYRQHAQPPKPSSDSSGGRSSAPYFSAECPDPPKTDLSRESIPLNDLKSEVS
                PRISAEDLIDLCELTVTGHFKTPSKKTKSSKPKLLVVDILNSEDFIRGHISGSINIPF
                SAAFTAEGELTQGPYTAMLQNFKGKVIVIVGHVAKHTAEFAAHLVKMKYPRTCILDGG
                INKIKPTGLLTIPSPQI

[0495] Further analysis of the NOV38a protein yielded the following properties shown in Table 38B.

TABLE 38B
Protein Sequence Properties NOV38a
PSort     0.8500 probability located in endoplasmic
analysis: reticulum (membrane); 0.4400
          probability located in plasma membrane;
          0.3362 probability located in
          microbody (peroxisome); 0.1000 probability
          located in mitochondrial inner
          membrane
SignalP   No Known Signal Sequence Predicted
analysis:

[0496] 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.

TABLE 38C
Geneseq Results for NOV38a
		NOV38a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length [Patent	Match	the Matched	Expect
Identifier	#, Date]	Residues	Region	Value
AAB62179	Human p100 protein - Homo	87 . . . 829	741/743 (99%)	0.0
	sapiens, 892 aa. [WO200120022-	150 . . . 892	742/743 (99%)
	A1, 22-MAR-2001]
AAB98890	Novel human (NHP) protein that	87 . . . 829	738/744 (99%)	0.0
	has homology to animal kinases -	150 . . . 893	740/744 (99%)
	Homo sapiens, 893 aa.
	[WO200134783-A1, 17-MAY-2001]
AAG67396	Amino acid sequence of human	87 . . . 829	738/744 (99%)	0.0
`	protein kinase SGK382 - Homo	150 . . . 893	740/744 (99%)
	sapiens, 893 aa. [WO200166594-
	A2, 13-SEP-2001]
ABB07503	Human GTP-binding protein	198 . . . 829	629/633 (99%)	0.0
	(GTPB) (ID: 3580727CD1) - Homo	4 . . . 636	630/633 (99%)
	sapiens, 636 aa. [WO200204510-
	A2, 17-JAN-2002]
AAM38995	Human polypeptide SEQ ID NO:	205 . . . 829	610/627 (97%)	0.0
	2140 - Homo sapiens, 627 aa.	1 . . . 627	612/627 (97%)
	[WO200153312-A1, 26-JUL-2001]

[0497] In a BLAST search of public sequence datbases, the NOV38a protein was found to have homology to the proteins shown in the BLASTP data in Table 38D.

TABLE 38D
Public BLASTP Results for NOV38a
		NOV38a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q96GV6	UNKNOWN (PROTEIN FOR	9 . . . 829	818/822 (99%)	0.0
	MGC: 16169) - Homo sapiens	1 . . . 822	819/822 (99%)
	(Human), 822 aa.
BAB85045	CDNA FLJ23725 FIS, CLONE	87 . . . 829	738/744 (99%)	0.0
	HEP14024 - Homo sapiens	150 . . . 893	740/744 (99%)
	(Human), 893 aa.
Q9P080	HSPC302 - Homo sapiens	325 . . . 829	479/507 (94%)	0.0
	(Human), 507 aa (fragment).	1 . . . 507	481/507 (94%)
Q9W4F8	CG4041 PROTEIN - Drosophila	5 . . . 802	353/854 (41%)	e−169
	melanogaster (Fruit fly), 840 aa.	8 . . . 794	468/854 (54%)
Q8WW57	SIMILAR TO HYPOTHETICAL	543 . . . 829	285/287 (99%)	e−167
	PROTEIN MGC16169 - Homo	14 . . . 300	286/287 (99%)
	sapiens (Human), 300 aa
	(fragment).

[0498] PFam analysis predicts that the NOV38a protein contains the domains shown in the Table 38E.

TABLE 38E
Domain Analysis of NOV38a
		Identities/
		Similarities
	NOV38a	for the	Expect
Pfam Domain	Match Region	Matched Region	Value
pkinase	93 . . . 210	38/140 (27%)	2e−17
		87/140 (62%)
TBC	399 . . . 609	63/343 (18%)	1e−26
		153/343 (45%)
Rhodanese	712 . . . 819	29/136 (21%)	0.00039
		76/136 (56%)

Example 39

[0499] The NOV39 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 39A.

TABLE 39A
NOV39 Sequence Analysis
                 SEQ ID NO:87         1136 bp
NOV39a,          ACACCTTTCTAAAAAGACTCCCTGTGGTGTTCAGAATCACTCCTACAGTCAGGTTCTC
CG97068-02       CACAATGGATCTCAGTGCTGCAAGTCACCGCATACCTCTAAGTGATGGAAACAGCATT
DNA Sequence     CCCATCATCGGACTTGGTACCTACTCAGAACCTAAATCGACCCCTAAGGGAGCCTGTG
                 CAACATCGGTGAAGGTTGCTATTGACACAGGGTACCGACATATTGATGGGGCCTACAT
                 CTACCAAAATGAACACGAAGTTGGGGAGGCCATCAGGGAGAAGATAGCAGAAGGAAAG
                 GTGCGGAGGGAAGATATCTTCTACTGTGGAAAGCTATGGGCTACAAATCATGTCCCAG
                 AGATGGTCCGCCCAACCCTGGAGAGGACACTCAGGGTCCTCCAGCTAGATTATGTGGA
                 TCCTTACATCATTGAAGTACCCATGGCCTTTAAGCCAGGAGATGAAATATACCCTAGA
                 GATGAGAATGGCAAATGGTTATATCACAAGTCAGATCTGTGTGCCACTTGGGAGGCGA
                 TGGAAGCTTGCAAAGACGCTGGCTTGGTGAAATCCCTGGGAGTGTCCAATTTTAACCG
                 CAGGCAGCTGGAGCTCATCCTGAACAAGCCAGGACTCAAACACAAGCCAGTCAGCAAC
                 CAGGTTGAGTGCCATCCGTATTTCACCCAGCCAAAACTCTTGAAATTTTGCCAACAAC
                 ATGACATTGTCATTACTGCATATAGCCCTTTGGGGACCAGTAGGAATCCAATCTCGGT
                 GAATGTTTCTTCTCCACCTTTGTTAAAGGATGCACTTCTAAACTCATTGGGGAAAAGG
                 TACAATAAGACAGCAGCTCAAATTGTTTTGCGTTTCAACATCCAGCGAGGGGTGGTTG
                 TCATTCCTAAAAGCTTTAATCTTGAAAGGATCAAAGAAAATTTTCAGATCTTTGACTT
                 TTCTCTCACTGAAGAAGAAATGAAGGACATTGAAGCCTTGAATAAAAATGTCCGCTTT
                 GTAGAATTGCTCATGTGGCGCGATCATCCTGAATACCCATTTCATGATGAATACTGAC
                 TGCCGGGAGTTCCTGAACAGATTTTTCACTCCCATGAGTCCCAAGACGGTGCAATGGG
                 TAGTCCCCTAGATGTGAAAATGAAGAGAGAGGGT
                 ORF Start: ATG at 63 ORF Stop: TGA at 1041
                 SEQ ID NO:88         326 aa MW at 37361.5 kD
NOV39a,          MDLSAASHRIPLSDGNSIPIIGLGTYSEPKSTPKGACATSVKVAIDTGYRHIDGAYIY
CG97068-02       QNEHEVGEAIREKIAEGKVRREDIFYCGKLWATNHVPEMVRPTLERTLRVLQLDYVDP
Protein Sequence YIIEVPMAFKPGDEIYPRDENGKWLYHKSDLCATWEAMEACKDAGLVKSLGVSNFNRR
                 QLELILNKPGLKHKPVSNQVECHPYFTQPKLLKFCQQHDIVITAYSPLGTSRNPIWVN
                 VSSPPLLKDALLNSLGKRYNKTAAQIVLRFNIQRGVVVIPKSFNLERIKENFQIFDFS
                 LTEEEMKDIEALNKNVRFVELLMWRDHPEYPFHDEY

[0500] Further analysis of the NOV39a protein yielded the following properties shown in Table 39B.

TABLE 39B
Protein Sequence Properties NOV39a
PSort     0.6500 probability located in cytoplasm;
analysis: 0.1000 probability located in
          mitochondrial matrix space; 0.1000
          probability located in lysosome (lumen);
          0.0000 probability located in endoplasmic
          reticulum (membrane)
SignalP   No Known Signal Sequence Predicted
analysis:

[0501] 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.

TABLE 39C
Geneseq Results for NOV39a
		NOV39a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
ABG06369	Novel human diagnostic protein	1 . . . 326	324/326 (99%)	0.0
	#6360 - Homo sapiens, 347 aa.	22 . . . 347	325/326 (99%)
	[WO200175067-A2, 11-OCT-2001]
ABG06369	Novel human diagnostic protein	1 . . . 326	324/326 (99%)	0.0
	#6360 - Homo sapiens, 347 aa.	22 . . . 347	325/326 (99%)
	[WO200175067-A2, 11-OCT-2001]
AAR55551	Delta(4)-3-ketosteroid-5-beta-	1 . . . 326	257/327 (78%)	e−153
	reductase - Synthetic, 326 aa.	1 . . . 326	290/327 (88%)
	[JP06121673-A, 06-MAY-1994]
AAB43444	Human cancer associated protein	10 . . . 326	184/317 (58%)	e−109
	sequence SEQ ID NO: 889 - Homo	21 . . . 336	240/317 (75%)
	sapiens, 336 aa. [WO200055350-
	A1, 21-SEP-2000]
AAM79455	Human protein SEQ ID NO: 3101 -	10 . . . 326	178/317 (56%)	e−107
	Homo sapiens, 325 aa.	10 . . . 325	238/317 (74%)
	[WO200157190-A2, 09-AUG-2001]

[0502] In a BLAST search of public sequence datbases, the NOV39a protein was found to have homology to the proteins shown in the BLASTP data in Table 39D.

TABLE 39D
Public BLASTP Results for NOV39a
		NOV39a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
P51857	3-oxo-5-beta-steroid 4-	1 . . . 326	324/326 (99%)	0.0
	dehydrogenase (EC 1.3.99.6)	1 . . . 326	325/326 (99%)
	(Delta(4)-3-ketosteroid 5-beta-
	reductase) (Aldo-keto reductase
	family 1 member D1) - Homo
	sapiens (Human), 326 aa.
Q9TV64	DELTA4-3-OXOSTEROID 5BETA-	1 . . . 326	290/326 (88%)	e−178
	REDUCTASE - Oryctolagus	1 . . . 326	310/326 (94%)
	cuniculus (Rabbit), 326 aa.
Q8VCX1	SIMILAR TO ALDO-KETO	1 . . . 326	267/326 (81%)	e−159
	REDUCTASE FAMILY 1,	1 . . . 325	293/326 (88%)
	MEMBER D1 (DELTA 4-3-
	KETOSTEROID-5-BETA-
	REDUCTASE) - Mus musculus
	(Mouse), 325 aa.
P31210	3-oxo-5-beta-steroid 4-	1 . . . 326	258/327 (78%)	e−153
	dehydrogenase (EC 1.3.99.6)	1 . . . 326	291/327 (88%)
	(Delta(4)-3-ketosteroid 5-beta-
	reductase) (Aldo-keto reductase
	family 1 member D1) - Rattus
	norvegicus (Rat), 326 aa.
P70694	Estradiol 17 beta-dehydrogenase, A-	3 . . . 326	190/324 (58%)	e−111
	specific (EC 1.1.1.-) (17-beta-HSD) -	1 . . . 323	241/324 (73%)
	Mus musculus (Mouse), 323 aa.

[0503] PFam analysis predicts that the NOV39a protein contains the domains shown in the Table 39E.

TABLE 39E
Domain Analysis of NOV39a
	NOV39a	Identities/
	Match	Similarities	Expect
Pfam Domain	Region	for the Matched Region	Value
aldo_ket_red	12 . . . 306	154/368 (42%)	1.5e−146
		262/368 (71%)

Example B

[0504] Identification of NOVX Clones

[0505] The novel NOVX target sequences identified in the present invention may have been 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. 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.

[0506] 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.

Example C

[0507] Quantitative Expression Analysis of Clones in Various Cells and Tissues

[0508] 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 autoinflammatory diseases), Panel CNSD.01 (containing samples from normal and diseased brains) and CNS_neurodegeneration_panel (containing samples from normal and Alzheimer's diseased brains).

[0509] 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.

[0510] 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.

[0511] 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.

[0512] 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.

[0513] 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.

[0514] 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.

[0515] Panels 1, 1.1, 1.2, and 1.3D

[0516] 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.

[0517] In the results for Panels 1, 1.1, 1.2 and 1.3D, the following abbreviations are used:

[0518] ca.=carcinoma,

[0519] *=established from metastasis,

[0520] met=metastasis,

[0521] s cell var=small cell variant,

[0522] non-s=non-sm=non-small,

[0523] squam=squamous,

[0524] pl. eff=pl effusion=pleural effusion,

[0525] glio=glioma,

[0526] astro=astrocytoma, and

[0527] neuro=neuroblastoma.

[0528] General_screening_panel_v1.4, v1.5 and v1.6

[0529] The plates for Panels 1.4, 1.5, and 1.6 include 2 control wells (genomic DNA control and chemistry control) and 94 wells containing cDNA from various samples. The samples in Panels 1.4, 1.5, and 1.6 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 Panels 1.4, 1.5, and 1.6 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 Panels 1.4, 1.5, and 1.6 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 1.3D.

[0530] Panels 2D, 2.2, 2.3 and 2.4

[0531] The plates for Panels 2D, 2.2, 2.3 and 2.4 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) or from Ardais or Clinomics). 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/CHTN/Ardais/Clinomics). Unmatched RNA samples from tissues without malignancy (normal tissues) were also obtained from Ardais or Clinomics. 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.

[0532] HASS Panel v 1.0

[0533] The HASS panel v 1.0 plates are comprised of 93 cDNA samples and two controls. Specifically, 81 of these samples are derived from cultured human cancer cell lines that had been subjected to serum starvation, acidosis and anoxia for different time periods as well as controls for these treatments, 3 samples of human primary cells, 9 samples of malignant brain cancer (4 medulloblastomas and 5 glioblastomas) and 2 controls. The human cancer cell lines are obtained from ATCC (American Type Culture Collection) and fall into the following tissue groups: breast cancer, prostate cancer, bladder carcinomas, pancreatic cancers and CNS cancer cell lines. These cancer cells are all cultured under standard recommended conditions. The treatments used (serum starvation, acidosis and anoxia) have been previously published in the scientific literature. The primary human cells were obtained from Clonetics (Walkersville, Md.) and were grown in the media and conditions recommended by Clonetics. The malignant brain cancer samples are obtained as part of a collaboration (Henry Ford Cancer Center) and are evaluated by a pathologist prior to CuraGen receiving the samples. RNA was prepared from these samples using the standard procedures. The genomic and chemistry control wells have been described previously.

[0534] Panel 3D and 3.1

[0535] The plates of Panel 3D and 3.1 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, 3.1 and 1.3D are of the most common cell lines used in the scientific literature.

[0536] Panels 4D, 4R, and 4.1D

[0537] 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.).

[0538] 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.

[0539] 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 5.5×1031 5M (Gibco), and 10 mM Hepes (Gibco) with PHA (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 2×106 cells/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.

[0540] 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, UT), 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 GMCSF 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.

[0541] CD4 lymphocytes, CD8 lymphocytes and NK cells were also isolated from mononuclear cells using CD4, CD8 and CD56 Miltenyi beads, positive VS selection columns 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 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 plated at 106 cells/ml onto Falcon 6 well tissue culture plates that had been coated overnight with 0.5 μg/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 5.5×10−5M (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.

[0542] 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 106 cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5(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.

[0543] To prepare the primary and secondary Th1/Th2 and Tr1 cells, six-well Falcon plates were coated overnight with 10 μg/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 105-106 cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5 M (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), 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 (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 (1 μg/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.

[0544] 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 5×105 cells/ml for 8 days, changing the media every 3 days and adjusting the cell concentration to 5×105 cells/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). CCD 1106 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.

[0545] For these cell lines and blood cells, RNA was prepared by lysing approximately 107 cells/ml using Trizol (Gibco BRL). Briefly, 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 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.

[0546] AI_comprehensive panel_v1.0

[0547] 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.

[0548] 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.

[0549] 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.

[0550] 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.

[0551] 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-1anti-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.

[0552] In the labels employed to identify tissues in the AI_comprehensive panel_v1.0 panel, the following abbreviations are used:

[0553] AI=Autoimmunity

[0554] Syn=Synovial

[0555] Normal=No apparent disease

[0556] Rep22 /Rep20=individual patients

[0557] RA=Rheumatoid arthritis

[0558] Backus=From Backus Hospital

[0559] OA=Osteoarthritis

[0560] (SS)(BA)(MF)=Individual patients

[0561] Adj=Adjacent tissue

[0562] Match control=adjacent tissues

[0563] −M=Male

[0564] −F=Female

[0565] COPD=Chronic obstructive pulmonary disease

[0566] Panels 5D and 51

[0567] 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.

[0568] 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:

[0569] Patient 2: Diabetic Hispanic, overweight, not on insulin

[0570] Patient 7-9: Nondiabetic Caucasian and obese (BMI>30)

[0571] Patient 10: Diabetic Hispanic, overweight, on insulin

[0572] Patient 11: Nondiabetic African American and overweight

[0573] Patient 12: Diabetic Hispanic on insulin

[0574] Adiocyte 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:

[0575] Donor 2 and 3 U: Mesenchymal Stem cells, Undifferentiated Adipose

[0576] Donor 2 and 3 AM: Adipose, AdiposeMidway Differentiated

[0577] Donor 2 and 3 AD: Adipose, Adipose Differentiated

[0578] 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.

[0579] 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.

[0580] In the labels employed to identify tissues in the 5D and 5I panels, the following abbreviations are used:

[0581] GO Adipose=Greater Omentum Adipose

[0582] SK=Skeletal Muscle

[0583] UT=Uterus

[0584] PL=Placenta

[0585] AD Adipose Differentiated

[0586] AM=Adipose Midway Differentiated

[0587] U=Undifferentiated Stem Cells

[0588] Panel CNSD.01

[0589] 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.

[0590] 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 Supemuclear 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.

[0591] In the labels employed to identify tissues in the CNS panel, the following abbreviations are used:

[0592] PSP=Progressive supranuclear palsy

[0593] Sub Nigra=Substantia nigra

[0594] Glob Palladus=Globus palladus

[0595] Temp Pole=Temporal pole

[0596] Cing Gyr=Cingulate gyrus

[0597] BA 4=Brodman Area 4

[0598] Panel CNS_Neurodegeneration_V1.0

[0599] 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.

[0600] Disease diagnoses are taken from patient records. The panel contains six brains from Alzheimei'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.

[0601] In the labels employed to identify tissues in the CNS_Neurodegeneration_V1.0 panel, the following abbreviations are used:

[0602] AD=Alzheimer's disease brain; patient was demented and showed AD-like pathology upon autopsy

[0603] Control=Control brains; patient not demented, showing no neuropathology

[0604] Control (Path)=Control brains; pateint not demented but showing sever AD-like pathology

[0605] SupTemporal Ctx=Superior Temporal Cortex

[0606] Inf Temporal Ctx=Inferior Temporal Cortex

A. CG100570-01: LRR Protein (Novel Secreted Protein)

[0607] Expression of gene CG100570-01 was assessed using the primer-probe set Ag4181, described in Table AA. Results of the RTQ-PCR runs are shown in Tables AB, AC, AD, AE and AF.

TABLE AA
Probe Name Ag4181
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-agttaagaggaaatgccattgg-3′	22	3338	89
Probe	TET-5′-agccaaagccctggcaaatgctct-3′-TAMRA	24	3369	90
Reverse	5′-tccggagacttgagtttacctt-3′	22	3394	91

[0608]

TABLE AB
AI_comprehensive panel_v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4181,		Ag4181,
Tissue Name	Run 212650186	Tissue Name	Run 212650186
110967 COPD-F	2.9	112427 Match Control	12.8
		Psoriasis-F
110980 COPD-F	4.4	112418 Psoriasis-M	2.9
110968 COPD-M	4.6	112723 Match Control	3.1
		Psoriasis-M
110977 COPD-M	12.5	112419 Psoriasis-M	1.9
110989	13.6	112424 Match Control	2.2
Emphysema-F		Psoriasis-M
110992	7.2	112420 Psoriasis-M	21.9
Emphysema-F
110993	6.8	112425 Match Control	8.0
Emphysema-F		Psoriasis-M
110994	3.2	104689 (MF) OA	8.9
Emphysema-F		Bone-Backus
110995	15.5	104690 (MF) Adj	3.3
Emphysema-F		“Normal” Bone-Backus
110996	4.6	104691 (MF) OA	2.2
Emphysema-F		Synovium-Backus
110997 Asthma-M	4.0	104692 (BA) OA	2.7
		Cartilage-Backus
111001 Asthma-F	6.7	104694 (BA) OA	4.5
		Bone-Backus
111002 Asthma-F	8.5	104695 (BA) Adj	4.0
		“Normal” Bone-
		Backus
111003 Atopic	6.9	104696 (BA) OA	1.0
Asthma-F		Synovium-Backus
111004 Atopic	10.4	104700 (SS) OA	4.7
Asthma-F		Bone-Backus
111005 Atopic	4.8	104701 (SS) Adj	3.8
Asthma-F		“Normal” Bone-
		Backus
111006 Atopic	1.7	104702 (SS) OA	5.4
Asthma-F		Synovium-Backus
111417 Allergy-M	5.8	117093 OA Cartilage	6.8
		Rep7
112347 Allergy-M	0.2	112672 OA Bone5	13.9
112349 Normal	0.1	112673 OA	3.6
Lung-F		Synovium5
112357 Normal	13.4	112674 OA Synovial	5.7
Lung-F		Fluid cells5
112354 Normal Lung-M	4.9	117100 OA Cartilage	0.8
		Rep14
112374 Crohns-F	0.0	112756 OA Bone9	1.0
112389 Match	4.2	112757 OA	3.6
Control Crohns-F		Synovium9
112375 Crohns-F	5.0	112758 OA Synovial	3.1
		Fluid Cells9
112732 Match	58.2	117125 RA Cartilage	4.2
Control Crohns-F		Rep2
112725 Crohns-M	0.7	113492 Bone2 RA	17.8
112387 Match	2.8	113493 Synovium2	5.4
Control Crohns-M		RA
112378 Crohns-M	0.1	113494 Syn Fluid	9.8
		Cells RA
112390 Match	21.6	113499 Cartilage4 RA	12.7
Control Crohns-M
112726 Crohns-M	6.4	113500 Bone4 RA	14.4
112731 Match	4.8	113501 Synovium4	7.6
Control Crohns-M		RA
112380 Ulcer Col-F	5.7	113502 Syn Fluid	6.7
		Cells4 RA
112734 Match	100.0	113495 Cartilage3 RA	7.0
Control Ulcer Col-F
112384 Ulcer Col-F	22.7	113496 Bone3 RA	10.7
112737 Match	2.2	113497 Synovium3	6.8
Control Ulcer Col-F		RA
112386 Ulcer Col-F	3.1	113498 Syn Fluid	13.5
		Cells3 RA
112738 Match	4.0	117106 Normal	3.2
Control Ulcer Col-F		Cartilage Rep20
112381 Ulcer Col-M	0.3	113663 Bone3 Normal	0.0
112735 Match	2.7	113664 Synovium3	0.0
Control Ulcer Col-M		Normal
112382 Ulcer Col-M	6.0	113665 Syn Fluid	0.2
		Cells3 Normal
112394 Match	1.3	117107 Normal	2.9
Control Ulcer Col-M		Cartilage Rep22
112383 Ulcer Col-M	9.9	113667 Bone4 Normal	7.1
112736 Match	1.3	113668 Synovium4	4.2
Control Ulcer Col-M		Normal
112423 Psoriasis-F	4.2	113669 Syn Fluid Cells4	6.6
		Normal

[0609]

TABLE AC
CNS_neurodegeneration_v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4181,		Ag4181,
	Run		Run
Tissue Name	215539691	Tissue Name	215539691
AD 1 Hippo	31.0	Control (Path) 3	3.2
		Temporal Ctx
AD 2 Hippo	26.1	Control (Path) 4	28.5
		Temporal Ctx
AD 3 Hippo	12.3	AD 1 Occipital Ctx	23.7
AD 4 Hippo	4.0	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 Hippo	93.3	AD 3 Occipital Ctx	9.9
AD 6 Hippo	60.7	AD 4 Occipital Ctx	6.7
Control 2 Hippo	8.2	AD 5 Occipital Ctx	20.7
Control 4 Hippo	15.5	AD 6 Occipital Ctx	9.5
Control (Path) 3	4.7	Control 1 Occipital	6.2
Hippo		Ctx
AD 1 Temporal Ctx	20.3	Control 2 Occipital	47.3
		Ctx
AD 2 Temporal Ctx	21.5	Control 3 Occipital	13.5
		Ctx
AD 3 Temporal Ctx	11.0	Control 4 Occipital	12.2
		Ctx
AD 4 Temporal Ctx	40.9	Control (Path) 1	100.0
		Occipital Ctx
AD 5 Inf Temporal	94.0	Control (Path) 2	21.9
Ctx		Occipital Ctx
AD 5 Sup Temporal	52.9	Control (Path) 3	1.5
Ctx		Occipital Ctx
AD 6 Inf Temporal	45.1	Control (Path) 4	20.6
Ctx		Occipital Ctx
AD 6 Sup Temporal	85.9	Control 1 Parietal Ctx	12.1
Ctx
Control 1 Temporal	4.1	Control 2 Parietal Ctx	45.1
Ctx
Control 2 Temporal	29.5	Control 3 Parietal Ctx	20.6
Ctx
Control 3 Temporal	3.9	Control (Path) 1	32.1
Ctx		Parietal Ctx
Control 3 Temporal	9.7	Control (Path) 2	22.2
Ctx		Parietal Ctx
Control (Path) 1	37.6	Control (Path) 3	4.4
Temporal Ctx		Parietal Ctx
Control (Path) 2	38.7	Control (Path) 4	54.7
Temporal Ctx		Parietal Ctx

[0610]

TABLE AD
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4181,		Ag4181, Run
Tissue Name	Run 212717379	Tissue Name	212717379
Adipose	11.7	Renal ca. TK-10	7.9
Melanoma*	1.6	Bladder	19.8
Hs688(A).T
Melanoma*	0.8	Gastric ca. (liver met.)	27.7
Hs688(B).T		NCI-N87
Melanoma* M14	1.3	Gastric ca. KATO III	2.6
Melanoma*	2.4	Colon ca. SW-948	2.2
LOXIMVI
Melanoma* SK-MEL-5	1.8	Colon ca. SW480	6.2
Squamous cell	0.4	Colon ca.* (SW480 met)	5.1
carcinoma SCC-4		SW620
Testis Pool	11.3	Colon ca. HT29	0.8
Prostate ca.* (bone	1.9	Colon ca. HCT-116	9.4
met) PC-3
Prostate Pool	7.2	Colon ca. CaCo-2	6.3
Placenta	3.2	Colon cancer tissue	7.2
Uterus Pool	3.3	Colon ca. SW1116	4.6
Ovarian ca. OVCAR-3	1.9	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	21.9	Colon ca. SW-48	0.9
Ovarian ca. OVCAR-4	1.3	Colon Pool	29.5
Ovarian ca. OVCAR-5	30.4	Small Intestine Pool	3.1
Ovarian ca. IGROV-1	5.0	Stomach Pool	14.9
Ovarian ca. OVCAR-8	3.9	Bone Marrow Pool	12.5
Ovary	11.8	Fetal Heart	14.4
Breast ca. MCF-7	5.3	Heart Pool	12.2
Breast ca. MDA-MB-	6.3	Lymph Node Pool	26.8
231
Breast ca. BT 549	1.7	Fetal Skeletal Muscle	7.4
Breast ca. T47D	36.1	Skeletal Muscle Pool	14.5
Breast ca. MDA-N	0.5	Spleen Pool	55.1
Breast Pool	25.2	Thymus Pool	100.0
Trachea	26.1	CNS cancer (glio/astro)	0.8
		U87-MG
Lung	3.2	CNS cancer (glio/astro)	6.6
		U-118-MG
Fetal Lung	55.1	CNS cancer (neuro; met)	5.4
		SK-N-AS
Lung ca. NCI-N417	0.8	CNS cancer (astro) SF-	0.7
		539
Lung ca. LX-1	11.2	CNS cancer (astro) SNB-	6.1
		75
Lung ca. NCI-H146	1.9	CNS cancer (glio) SNB-	2.4
		19
Lung ca. SHP-77	5.8	CNS cancer (glio) SF-	18.0
		295
Lung ca. A549	5.7	Brain (Amygdala) Pool	3.3
Lung ca. NCI-H526	0.5	Brain (cerebellum)	15.0
Lung ca. NCI-H23	20.9	Brain (fetal)	13.5
Lung ca. NCI-H460	8.1	Brain (Hippocampus)	3.7
		Pool
Lung ca. HOP-62	1.8	Cerebral Cortex Pool	7.3
Lung ca. NCI-H522	6.7	Brain (Substantia nigra)	6.2
		Pool
Liver	1.8	Brain (Thalamus) Pool	10.0
Fetal Liver	6.0	Brain (whole)	5.2
Liver ca. HepG2	3.4	Spinal Cord Pool	9.3
Kidney Pool	32.5	Adrenal Gland	5.3
Fetal Kidney	23.2	Pituitary gland Pool	2.9
Renal ca. 786-0	2.9	Salivary Gland	5.5
Renal ca. A498	9.0	Thyroid (female)	5.9
Renal ca. ACHN	6.7	Pancreatic ca. CAPAN2	6.5
Renal ca. UO-31	6.2	Pancreas Pool	30.1

[0611]

TABLE AE
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4181, Run		Ag4181, Run
Tissue Name	173607818	Tissue Name	173607818
Secondary Th1 act	34.6	HUVEC IL-1beta	0.6
Secondary Th2 act	35.6	HUVEC IFN gamma	1.6
Secondary Tr1 act	35.8	HUVEC TNF alpha +	0.2
		IFN gamma
Secondary Th1 rest	35.8	HUVEC TNF alpha +	0.1
		IL4
Secondary Th2 rest	49.7	HUVEC IL-11	0.7
Secondary Tr1 rest	64.6	Lung Microvascular EC	6.3
		none
Primary Th1 act	12.8	Lung Microvascular EC	1.3
		TNF alpha + IL-1beta
Primary Th2 act	27.5	Microvascular Dermal	0.3
		EC none
Primary Tr1 act	16.7	Microsvasular Dermal	0.3
		EC TNF alpha + IL-1beta
Primary Th1 rest	37.9	Bronchial epithelium	0.2
		TNF alpha + IL1beta
Primary Th2 rest	33.2	Small airway epithelium	0.1
		none
Primary Tr1 rest	54.3	Small airway epithelium	0.1
		TNF alpha + IL-1beta
CD45RA CD4	10.7	Coronery artery SMC	0.3
lymphocyte act		rest
CD45RO CD4	36.1	Coronery artery SMC	0.0
lymphocyte act		TNF alpha + IL-1beta
CD8 lymphocyte act	27.9	Astrocytes rest	0.5
Secondary CD8	19.3	Astrocytes TNF alpha +	0.1
lymphocyte rest		IL-1beta
Secondary CD8	18.8	KU-812 (Basophil) rest	5.4
lymphocyte act
CD4 lymphocyte none	28.7	KU-812 (Basophil)	4.9
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	100.0	CCD1106	0.2
CD95 CH11		(Keratinocytes) none
LAK cells rest	21.9	CCD1106	0.4
		(Keratinocytes)
		TNF alpha + IL-1beta
LAK cells IL-2	44.4	Liver cirrhosis	0.5
LAK cells IL-2 + IL-12	19.1	NCI-H292 none	0.3
LAK cells IL-2 + IFN	14.5	NCI-H292 IL-4	0.5
gamma
LAK cells IL-2 + IL-18	24.7	NCI-H292 IL-9	1.0
LAK cells	4.7	NCI-H292 IL-13	0.8
PMA/ionomycin
NK Cells IL-2 rest	90.1	NCI-H292 IFN gamma	0.9
Two Way MLR 3 day	29.5	HPAEC none	0.9
Two Way MLR 5 day	13.4	HPAEC TNF alpha + IL-	0.7
		1beta
Two Way MLR 7 day	24.8	Lung fibroblast none	1.1
PBMC rest	19.8	Lung fibroblast TNF	0.4
		alpha + IL-1beta
PBMC PWM	14.8	Lung fibroblast IL-4	0.6
PBMC PHA-L	16.6	Lung fibroblast IL-9	0.6
Ramos (B cell) none	32.8	Lung fibroblast IL-13	1.0
Ramos (B cell)	32.5	Lung fibroblast IFN	0.4
ionomycin		gamma
B lymphocytes PWM	8.8	Dermal fibroblast	3.4
		CCD1070 rest
B lymphocytes CD40L	29.7	Dermal fibroblast	55.5
and IL-4		CCD1070 TNF alpha
EOL-1 dbcAMP	21.6	Dermal fibroblast	0.2
		CCD1070 IL-1beta
EOL-1 dbcAMP	20.4	Dermal fibroblast IFN	0.8
PMA/ionomycin		gamma
Dendritic cells none	2.2	Dermal fibroblast IL-4	0.3
Dendritic cells LPS	0.9	Dermal fibroblasts rest	0.2
Dendritic cells anti-	0.0	Neutrophils TNFa + LPS	0.5
CD40
Monocytes rest	0.4	Neutrophils rest	0.9
Monocytes LPS	1.9	Colon	1.3
Macrophages rest	3.4	Lung	2.6
Macrophages LPS	0.5	Thymus	31.6
HUVEC none	0.6	Kidney	10.2
HUVEC starved	1.3

[0612]

TABLE AF
general oncology screening panel_v_2.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4181,		Ag4181,
Tissue Name	Run 260271995	Tissue Name	Run 260271995
Colon cancer 1	16.5	Bladder cancer NAT 2	0.7
Colon NAT 1	10.0	Bladder cancer NAT 3	0.6
Colon cancer 2	8.0	Bladder cancer NAT 4	0.6
Colon cancer NAT 2	3.0	Adenocarcinoma of the	41.2
		prostate 1
Colon cancer 3	6.2	Adenocarcinoma of the	0.9
		prostate 2
Colon cancer NAT 3	6.8	Adenocarcinoma of the	5.0
		prostate 3
Colon malignant	14.9	Adenocarcinoma of the	4.6
cancer 4		prostate 4
Colon normal adjacent	3.0	Prostate cancer NAT 5	1.1
tissue 4
Lung cancer 1	20.4	Adenocarcinoma of the	2.3
		prostate 6
Lung NAT 1	0.8	Adenocarcinoma of the	1.8
		prostate 7
Lung cancer 2	30.1	Adenocarcinoma of the	1.3
		prostate 8
Lung NAT 2	3.4	Adenocarcinoma of the	9.7
		prostate 9
Squamous cell	18.8	Prostate cancer NAT 10	1.4
carcinoma 3
Lung NAT 3	0.4	Kidney cancer 1	27.9
metastatic melanoma 1	12.9	Kidney NAT 1	15.2
Melanoma 2	1.5	Kidney cancer 2	100.0
Melanoma 3	0.7	Kidney NAT 2	4.7
metastatic melanoma 4	17.0	Kidney cancer 3	21.9
metastatic melanoma 5	33.0	Kidney NAT 3	2.0
Bladder cancer 1	0.7	Kidney cancer 4	9.7
Bladder cancer NAT 1	0.0	Kidney NAT 4	1.4
Bladder cancer 2	3.3

[0613] AI_comprehensive panel_v1.0 Summary: Ag4181 Highest expression of the CG100570-01 gene is seen in normal tissue adjacent to a disease sample of ulcerative colitis (CT=29.3). Overall, this gene is widely expressed on this panel, supporting the suggestion that this gene product may be involved in the autoimmune respones. Please see Panel 4.1D for discussion of this gene in autoimmune disease.

[0614] CNS_neurodegeneration_v1.0 Summary: Ag4181 The CG100570-01 gene appears to be upregulated in the temporal cortex of Alzheimer's disease patients. Therefore, therapeutic modulation of the expression or function of this protein may decrease neuronal death and be of use in the treatment of this disease.

[0615] General_screening_panel_v1.4 Summary: Ag4181 Highest expression of the CG100570-01 gene is seen in the thymus (CT=29.3). Significant levels of expression are also seen in ovarian cancer, breast cancer, and lung cancer cell lines. In addition, higher levels of expression are seen in fetal lung (CT=30.1) when compared to expression in the adult lung (CT=34). Thus, expression of this gene could be used to differentiate between adult and fetal lung tissue. Since fetal tissue and cell lines are generally more proliferative than adult tissue, this gene may be involved in cell proliferation, particularly in ovarian, breast and lung cancers. 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 these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of ovarian, breast and lung cancer.

[0616] 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 function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0617] This gene is also expressed at low levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum 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.

[0618] Panel 4.1D Summary: Ag4181 Highest expression of the CG100570-01 gene is seen in secondary Th1/TH2/Tr1 cells treated with anti-CD95 (CT=27.6). The CG100570-01 gene transcript is found in T cells and B cells, including resting and activated Th1, Th2 and Tr1 cells, resting and PWM stimulated B lymphocytes, the Ramos B cell line, PBMCs stimulated with PWM, and the thymus. LAK cells, dendritic cells and eosinophils also express this transcript at moderate levels. Dermal fibroblasts treated with TNF-alpha are the only non-hematopoietic cell type that prominently expresses this transcript. Thus, this transcript or the protein it encodes may be important in the function of B or T cells and could be used to detect hematopoietically-derived cells. Furthermore, therapeutics designed with the protein encoded by this transcript may potentially be important in the treatment of T and B cell mediated diseases, including asthma, emphysema, psoriasis, arthrtis, lupus, and inflammatory bowel disease (IBD).

[0619] General oncology screening panel_v—2.4 Summary: Ag4181 Expression of the CG100570-01 gene is highest in a sample derived from kidney cancer (CT=31.4). In addition, this gene is overexpressed in kidney cancer when compared to corresponding normal adjacent tissue. 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.

B. CG100750-01: LRR Protein (Novel Intracellular Protein)

[0620] Expression of gene CG100750-01 was assessed using the primer-probe set Ag4188, described in Table BA. Results of the RTQ-PCR runs are shown in Table BB.

TABLE BA
Probe Name Ag4188
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ggagttctctttcagcaaaggt-3′	22	244	92
Probe	TET-5′-tcctatgttttctatctcagctgcca-3′-TAMRA	26	268	93
Reverse	5′-tcagcaaaggtagtttccttca-3′	22	308	94

[0621]

TABLE BB
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4188, Run		Ag4188, Run
Tissue Name	182086762	Tissue Name	182086762
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	0.0
lymphocyte act		rest
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	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	2.0
PMA/ionomycin		gamma
Dendritic cells none	0.0	Dermal fibroblast IL-4	0.0
Dendritic cells LPS	0.0	Dermal Fibroblasts rest	0.6
Dendritic cells anti-	0.0	Neutrophils TNFa + LPS	0.0
CD40
Monocytes rest	0.0	Neutrophils rest	0.0
Monocytes LPS	0.0	Colon	1.7
Macrophages rest	0.0	Lung	2.1
Macrophages LPS	0.0	Thymus	6.6
HUVEC none	0.0	Kidney	100.0
HUVEC starved	0.0

[0622] Panel 4.1D Summary: Ag4188 This gene is only expressed at detectable levels in the kidney (CT=32.7). Thus, expression of this gene could be used to differentiate the kidney derived sample from other samples on this panel and as a marker of kidney tissue. In addition, therapeutic targeting of the expression or function of this gene may modulate kidney function and be important in the treatment of inflammatory or autoimmune diseases that affect the kidney, including lupus and glomerulonephritis.

C. CG101201-01: Novel Adenine Nucleotide Translocator 2 (ADP/ATP Translocase 2)

[0623] Expression of gene CG 101201-01 was assessed using the primer-probe set Ag4206, described in Table CA. Results of the RTQ-PCR runs are shown in Table CB.

TABLE CA
Probe Name Ag4206
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ccaaggctctaacaggtctgt-3′	21	553	95
Probe	TET-5′-tatcatctaccgagctgcctgcttcg-3′-TAMRA	26	593	96
Reverse	5′-tctccttgcagtgtcatagaca-3′	22	610	97

[0624]

TABLE CB
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4206, Run		Ag4206, Run
Tissue Name	174268918	Tissue Name	174268918
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	3.0
		TNF alpha + IL1beta
Primary Th2 rest	0.0	Small airway epithelium	6.4
		none
Primary Tr1 rest	0.0	Small airway epithelium	6.4
		TNF alpha + IL-1beta
CD45RA CD4	0.0	Coronery artery SMC	0.0
lymphocyte act		rest
CD45RO CD4	0.0	Coronery artery SMC	0.6
lymphocyte act		TNF alpha + IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	0.0
Secondary CD8	0.0	Astrocytes TNF alpha +	1.7
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	73.7
CD95 CH11		(Keratinocytes) none
LAK cells rest	0.0	CCD1106	6.2
		(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	9.9
LAK cells IL-2 + IFN	0.0	NCI-H292 IL-4	12.2
gamma
LAK cells IL-2 + IL-18	0.0	NCI-H292 IL-9	9.6
LAK cells	0.3	NCI-H292 IL-13	4.9
PMA/ionomycin
NK Cells IL-2 rest	0.0	NCI-H292 IFN gamma	1.8
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	1.1
PBMC PHA-L	0.0	Lung fibroblast IL-9	0.0
Ramos (B cell) none	0.0	Lung fibroblast IL-13	2.6
Ramos (B cell)	0.0	Lung fibroblast IFN	1.7
ionomycin		gamma
B lymphocytes PWM	0.0	Dermal fibroblast	1.5
		CCD1070 rest
B lymphocytes CD40L	0.0	Dermal fibroblast	0.0
and IL-4		CCD1070 TNF alpha
EOL-1 dbcAMP	0.0	Dermal fibroblast	4.0
		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	2.7	Colon	0.0
Macrophages rest	0.0	Lung	2.5
Macrophages LPS	0.0	Thymus	13.3
HUVEC none	1.2	Kidney	100.0
HUVEC starved	0.0

[0625] Panel 4.1D Summary: Ag4206 Highest expression of the CG101201-01 gene is detected in kidney (CT=30.76). Therefore, expression of this gene may be used to distinguish kidney from other samples used in this panel. Furthermore, therapeutic modulation of this gene may be beneficial in the treatment of autoimmune and inflammatory diseases that affect kidney including lupus and glomerulonephritis.

[0626] In addition, moderate to low levels of expression of this gene is also seen in thymus, NCI-H292, small airway epithelium and keratinocytes. Therefore, therapeutic modulation of this gene may be useful in the treatment of autoimmune and inflammatory diseases including chronic obstructive pulmonary disease, asthma, allergy, emphysema, psoriasis and wound healing.

[0627] This gene codes for homolog of adenine nucleotide translocator (ANT 2). Dysfunctioning of the ANT2 have been shown to induce myopathies in mouse and in humans (Fiore et al., 2001, Clin Chim Acta 311(2):125-35, PMID: 11566172). Therefore, based on homology dysfunctioning of the ANT2 homolog encoded by this gene may also contribute to myopathies in human and therapeutic modulation of this gene or its product may be useful in the treatment of this disease.

D. CG101211-01: Novel Protein containing the Mitochondrial Energy Transfer Protein Domain

[0628] Expression of gene CG 101211-01 was assessed using the primer-probe set Ag4207, described in Table DA. Results of the RTQ-PCR runs are shown in Tables DB, DC, DD and DE.

TABLE DA
Probe Name Ag4207
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ctgagaaaatggcatctgaaag-3′	22	3681	98
Probe	TET-5′-tgaaacacctactggagctatttcaca-3′-TAMRA	27	3703	99
Reverse	5′-tgacagaaggcatcctttctt-3′	21	3735	100

[0629]

TABLE DB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4207, Run		Ag4207, Run
Tissue Name	215601929	Tissue Name	215601929
AD 1 Hippo	13.5	Control (Path) 3	5.5
		Temporal Ctx
AD 2 Hippo	24.0	Control (Path) 4	30.1
		Temporal Ctx
AD 3 Hippo	7.2	AD 1 Occipital Ctx	14.5
AD 4 Hippo	6.0	AD 2 Occipital Ctx	0.1
		(Missing)
AD 5 hippo	43.2	AD 3 Occipital Ctx	9.2
AD 6 Hippo	46.3	AD 4 Occipital Ctx	13.2
Control 2 Hippo	25.2	AD 5 Occipital Ctx	11.5
Control 4 Hippo	8.4	AD 6 Occipital Ctx	100.0
Control (Path) 3 Hippo	9.4	Control 1 Occipital Ctx	5.7
AD 1 Temporal Ctx	17.3	Control 2 Occipital Ctx	63.3
AD 2 Temporal Ctx	32.5	Control 3 Occipital Ctx	13.1
AD 3 Temporal Ctx	6.3	Control 4 Occipital Ctx	6.4
AD 4 Temporal Ctx	17.6	Control (Path) 1	92.7
		Occipital Ctx
AD 5 Inf Temporal Ctx	36.1	Control (Path) 2	8.5
		Occipital Ctx
AD 5 Sup Temporal Ctx	19.1	Control (Path) 3	4.5
		Occipital Ctx
AD 6 Inf Temporal Ctx	51.1	Control (Path) 4	13.1
		Occipital Ctx
AD 6 Sup Temporal Ctx	48.6	Control 1 Parietal Ctx	8.0
Control 1 Temporal Ctx	3.6	Control 2 Parietal Ctx	22.4
Control 2 Temporal Ctx	40.9	Control 3 Parietal Ctx	16.2
Control 3 Temporal Ctx	9.9	Control (Path) 1 Parietal	85.9
		Ctx
Control 4 Temporal Ctx	8.6	Control (Path) 2 Parietal	18.0
		Ctx
Control (Path) 1 Temporal	51.4	Control (Path) 3 Parietal	5.8
Ctx		Ctx
Control (Path) 2 Temporal	24.1	Control (Path) 4 Parietal	36.1
Ctx		Ctx

[0630]

TABLE DC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4207,		Ag4207, Run
Tissue Name	Run 221254779	Tissue Name	221254779
Adipose	15.4	Renal ca.TK-10	35.6
Melanoma* Hs688(A).T	28.7	Bladder	24.3
Melanoma* Hs688(B).T	22.5	Gastric ca. (liver met.)	90.1
		NCI-N87
Melanoma* M14	12.2	Gastric ca. KATO III	33.9
Melanoma* LOXIMVI	19.2	Colon ca. SW-948	2.0
Melanoma* SK-MEL-5	35.6	Colon ca. SW480	24.1
Squamous cell carcinoma	20.3	Colon ca.* (SW480 met)	9.9
SCC-4		SW620
Testis Pool	27.5	Colon ca. HT29	11.9
Prostate ca.* (bone met)	43.2	Colon ca. HCT-116	4.3
PC-3
Prostate Pool	16.2	Colon ca. CaCo-2	11.7
Placenta	0.7	Colon cancer tissue	11.6
Uterus Pool	11.0	Colon ca. SW1116	5.3
Ovarian ca. OVCAR-3	41.8	Colon ca. Colo-205	2.7
Ovarian ca. SK-OV-3	42.3	Colon ca. SW-48	1.9
Ovarian ca. OVCAR-4	5.5	Colon Pool	39.2
Ovarian ca. OVCAR-5	74.7	Small Intestine Pool	32.8
Ovarian ca. IGROV-1	21.0	Stomach Pool	20.4
Ovarian ca. OVCAR-8	20.6	Bone Marrow Pool	10.3
Ovary	24.8	Fetal Heart	24.7
Breast ca. MCF-7	67.4	Heart Pool	17.8
Breast ca. MDA-MB-231	36.3	Lymph Node Pool	36.3
Breast ca. BT 549	83.5	Fetal Skeletal Muscle	15.8
Breast ca. T47D	100.0	Skeletal Muscle Pool	22.5
Breast ca. MDA-N	11.3	Spleen Pool	17.6
Breast Pool	43.5	Thymus Pool	31.6
Trachea	22.1	CNS cancer (glio/astro)	34.2
		U87-MG
Lung	9.9	CNS cancer (glio/astro)	44.8
		U-118-MG
Fetal Lung	65.1	CNS cancer (neuro; met)	49.3
		SK-N-AS
Lung ca. NCI-N417	4.7	CNS cancer (astro) SF-	16.3
		539
Lung ca. LX-1	8.3	CNS cancer (astro)	79.6
		SNB-75
Lung ca. NCI-H146	6.9	CNS cancer (glio) SNB-	14.0
		19
Lung ca. SHP-77	40.9	CNS cancer (glio) SF-	70.2
		295
Lung ca. A549	39.2	Brain (Amygdala) Pool	42.0
Lung ca. NCI-H526	7.5	Brain (cerebellum)	49.7
Lung ca. NCI-H23	48.0	Brain (fetal)	51.4
Lung ca. NCI-H460	28.3	Brain (Hippocampus)	44.1
		Pool
Lung ca. HOP-62	22.7	Cerebral Cortex Pool	53.6
Lung ca. NCI-H522	17.2	Brain (Substantia nigra)	33.7
		Pool
Liver	0.9	Brain (Thalamus) Pool	78.5
Fetal Liver	20.9	Brain (whole)	25.7
Liver ca. HepG2	15.6	Spinal Cord Pool	28.7
Kidney Pool	66.9	Adrenal Gland	6.1
Fetal Kidney	55.1	Pituitary gland Pool	10.7
Renal ca. 786-0	13.5	Salivary Gland	1.9
Renal ca. A498	9.0	Thyroid (female)	25.9
Renal ca. ACHN	17.9	Pancreatic ca. CAPAN2	29.7
Renal ca. UO-31	12.4	Pancreas Pool	36.6

[0631]

TABLE DD
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4207, Run		Ag4207, Run
Tissue Name	175226748	Tissue Name	175226748
Secondary Th1 act	35.8	HUVEC IL-1beta	38.4
Secondary Th2 act	44.1	HUVEC IFN gamma	45.4
Secondary Tr1 act	28.5	HUVEC TNF alpha +	18.4
		IFN gamma
Secondary Th1 rest	18.2	HUVEC TNF alpha +	39.8
		IL4
Secondary Th2 rest	17.7	HUVEC IL-11	27.9
Secondary Tr1 rest	24.7	Lung Microvascular EC	66.9
		none
Primary Th1 act	11.8	Lung Microvascular EC	47.3
		TNF alpha + IL-1beta
Primary Th2 act	24.8	Microvascular Dermal	48.3
		EC none
Primary Tr1 act	17.6	Microsvasular Dermal	28.9
		EC TNF alpha + IL-1beta
Primary Th1 rest	12.9	Bronchial epithelium	39.5
		TNF alpha + IL1beta
Primary Th2 rest	15.7	Small airway epithelium	10.3
		none
Primary Tr1 rest	20.3	Small airway epithelium	21.6
		TNF alpha + IL-1beta
CD45RA CD4	28.3	Coronery artery SMC	26.6
lymphocyte act		rest
CD45RO CD4	38.2	Coronery artery SMC	22.2
lymphocyte act		TNF alpha + IL-1beta
CD8 lymphocyte act	17.3	Astrocytes rest	22.2
Secondary CD8	26.1	Astrocytes TNF alpha +	21.2
lymphocyte rest		IL-1beta
Secondary CD8	6.1	KU-812 (Basophil) rest	42.0
lymphocyte act
CD4 lymphocyte none	7.0	KU-812 (Basophil)	82.9
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	45.7	CCD1106	43.5
CD95 CH11		(Keratinocytes) none
LAK cells rest	24.1	CCD1106	19.8
		(Keratinocytes)
		TNF alpha + IL-1beta
LAK cells IL-2	31.0	Liver cirrhosis	12.5
LAK cells IL-2 + IL-12	18.6	NCI-H292 none	32.3
LAK cells IL-2 + IFN	16.7	NCI-H292 IL-4	46.7
gamma
LAK cells IL-2 + IL-18	21.8	NCI-H292 IL-9	100.0
LAK cells	25.2	NCI-H292 IL-13	73.2
PMA/ionomycin
NK Cells IL-2 rest	29.7	NCI-H292 IFN gamma	47.3
Two Way MLR 3 day	32.5	HPAEC none	30.4
Two Way MLR 5 day	22.5	HPAEC TNF alpha +	56.6
		IL-1beta
Two Way MLR 7 day	15.8	Lung fibroblast none	49.3
PBMC rest	4.8	Lung fibroblast TNF	40.6
		alpha + IL-1beta
PBMC PWM	15.8	Lung fibroblast IL-4	34.9
PBMC PHA-L	17.6	Lung fibroblast IL-9	61.1
Ramos (B cell) none	34.4	Lung fibroblast IL-13	39.2
Ramos (B cell) ionomycin	42.9	Lung fibroblast IFN	35.4
		gamma
B lymphocytes PWM	18.2	Dermal fibroblast	34.9
		CCD1070 rest
B lymphocytes CD40L	45.7	Dermal fibroblast	47.3
and IL-4		CCD1070 TNF alpha
EOL-1 dbcAMP	11.7	Dermal fibroblast	25.3
		CCD1070 IL-1beta
EOL-1 dbcAMP	15.2	Dermal fibroblast IFN	39.2
PMA/ionomycin		gamma
Dendritic cells none	38.4	Dermal fibroblast IL-4	67.4
Dendritic cells LPS	25.9	Dermal fibroblasts rest	45.4
Dendritic cells anti-CD40	39.8	Neutrophils TNFa + LPS	7.7
Monocytes rest	20.4	Neutrophils rest	5.7
Monocytes LPS	52.5	Colon	15.3
Macrophages rest	28.5	Lung	32.5
Macrophages LPS	14.2	Thymus	76.3
HUVEC none	27.4	Kidney	62.4
HUVEC starved	23.8

[0632]

TABLE DE
general oncology screening panel_v_2.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4207, Run		Ag4207, Run
Tissue Name	268624900	Tissue Name	268624900
Colon cancer 1	14.5	Bladder cancer NAT 2	1.6
Colon cancer NAT 1	7.3	Bladder cancer NAT 3	0.4
Colon cancer 2	12.4	Bladder cancer NAT 4	5.2
Colon cancer NAT 2	7.1	Adenocarcinoma of the	52.9
		prostate 1
Colon cancer 3	17.0	Adenocarcinoma of the	3.3
		prostate 2
Colon cancer NAT 3	22.7	Adenocarcinoma of the	14.2
		prostate 3
Colon malignant cancer 4	42.9	Adenocarcinoma of the	10.4
		prostate 4
Colon normal adjacent	5.6	Prostate cancer NAT 5	4.5
tissue 4
Lung cancer 1	13.7	Adenocarcinoma of the	4.4
		prostate 6
Lung NAT 1	2.9	Adenocarcinoma of the	6.6
		prostate 7
Lung cancer 2	34.4	Adenocarcinoma of the	2.0
		prostate 8
Lung NAT 2	3.2	Adenocarcinoma of the	27.7
		prostate 9
Squamous cell carcinoma 3	31.6	Prostate cancer NAT 10	1.5
Lung NAT 3	0.4	kidney cancer 1	16.5
metastatic melanoma 1	44.8	KidneyNAT 1	10.3
Melanoma 2	0.9	Kidney cancer 2	100.0
Melanoma 3	4.8	Kidney NAT 2	28.5
metastatic melanoma 4	80.7	Kidney cancer 3	28.9
metastatic melanoma 5	97.9	Kidney NAT 3	10.4
Bladder cancer 1	3.3	Kidney cancer 4	15.2
Bladder cancer NAT 1	0.0	Kidney NAT 4	10.4
Bladder cancer 2	9.9

[0633] CNS_neurodegeneration_v1.0 Summary: Ag4207 This panel confirms the expression of this gene in the brain. Please see Panel 1.4 for discussion of this gene in the central nervous system.

[0634] General_screening_panel_v1.4 Summary: Ag4207 Highest expression of this gene is seen in a breast cancer cell line (CT=27.1). This gene is widely expressed in this panel, with moderate expression seen in brain, colon, gastric, lung, breast, ovarian, and melanoma cancers. In addition, this gene is expressed at much higher levels in fetal lung and liver tissue (CTs=28-29) when compared to expression in the adult counterpart (CTs=30-33). Thus, expression of this gene may be used to differentiate between the fetal and adult source of these tissues. This expression profile suggests a role for this gene product in cell survival and proliferation. Therefore, modulation of this gene product may be useful in the treatment of cancer.

[0635] 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 function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0636] This gene is also expressed at high to moderate levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum 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.

[0637] Panel 4.1D Summary: Ag4207 Highest expression of this gene is seen in IL-9 treated NCI-H292 cells, pulmonary mucoepidermoid cell line (CT=30.1). This gene is expressed at moderate to low 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.

[0638] General oncology screening panel_v—2.4 Summary: Ag4207 Highest expression of this gene is seen in kidney cancer (CT=29.4). In addition, this gene is more highly expressed in lung and kidney cancer than in the corresponding normal adjacent tissue, with moderate levels of expression also seen in melanoma, prostate, and squamous cell cancers. Thus, expression of this gene could be used as a marker of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene product may be useful in the treatment of lung and kidney cancer.

E. CG101904-01: Cytosolic Phosphoprotein-like Proteins

[0639] Expression of gene CG101904-01 was assessed using the primer-probe set Ag4227, described in Table EA. Results of the RTQ-PCR runs are shown in Table EB.

TABLE EA
Probe Name Ag4227
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-atagtgcattggtggacaagac-3′	22	1256	101
Probe	TET-5′-agacaatgaaaacccctaagggcctg-3′-TAMRA	26	1289	102
Reverse	5′-caattcccatgatttctccttt-3′	22	1323	103

[0640]

TABLE EB
General_screening panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4227, Run		Ag4227, Run
Tissue Name	221297231	Tissue Name	221297231
Adipose	0.0	Renal ca. TK-10	2.6
Melanoma* Hs688(A).T	1.6	Bladder	1.4
Melanoma* Hs688(B).T	4.1	Gastric ca. (liver met.) NCI-	0.0
		N87
Melanoma* M14	0.0	Gastric ca. KATO III	0.0
Melanoma* LOXIMVI	1.3	Colon ca. SW-948	0.0
Melanoma* SK-MEL-5	1.9	Colon ca. SW480	2.8
Squamous cell carcinoma	0.0	Colon ca.* (SW480 met)	0.0
SCC-4		SW620
Testis Pool	100.0	Colon ca. HT29	0.0
Prostate ca.* (bone met)	2.2	Colon ca. HCT-116	1.1
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. OVCAR-3	0.0	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	2.3	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	0.0	Colon Pool	0.0
Ovarian ca. OVCAR-5	4.3	Small Intestine Pool	1.4
Ovarian ca. IGROV-1	0.0	Stomach Pool	0.0
Ovarian ca. OVCAR-8	0.0	Bone Marrow Pool	0.0
Ovary	0.0	Fetal Heart	1.1
Breast ca. MCF-7	0.0	Heart Pool	0.0
Breast ca. MDA-MB-231	1.5	Lymph Node Pool	0.0
Breast ca. BT 549	0.0	Fetal Skeletal Muscle	2.6
Breast ca. T47D	4.7	Skeletal Muscle Pool	0.0
Breast ca. MDA-N	0.0	Spleen Pool	0.0
Breast Pool	0.0	Thymus Pool	2.7
Trachea	22.2	CNS cancer (glio/astro)	0.0
		U87-MG
Lung	0.0	CNS cancer (glio/astro) U-	0.0
		118-MG
Fetal Lung	44.1	CNS cancer (neuro; met)	5.8
		SK-N-AS
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-539	0.0
Lung ca. LX-1	0.0	CNS cancer (astro) SNB-75	0.0
Lung ca. NCI-H146	0.0	CNS cancer (glio) SNB-19	1.3
Lung ca. SHP-77	0.0	CNS cancer (glio) SF-295	5.6
Lung ca. A549	0.0	Brain (Amygdala) Pool	0.0
Lung ca. NCI-H526	0.0	Brain (cerebellum)	0.0
Lung ca. NCI-H23	4.2	Brain (fetal)	1.7
Lung ca. NCI-H460	1.8	Brain (Hippocampus) Pool	1.3
Lung ca. HOP-62	0.0	Cerebral Cortex Pool	0.0
Lung ca. NCI-H522	0.0	Brain (Substantia nigra)	0.0
		Pool
Liver	0.0	Brain (Thalamus) Pool	2.1
Fetal Liver	0.0	Brain (whole)	0.0
Liver ca. HepG2	0.0	Spinal Cord Pool	2.4
Kidney Pool	0.0	Adrenal Gland	0.0
Fetal Kidney	1.6	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. CAPAN2	0.0
Renal ca. UO-31	0.0	Pancreas Pool	2.5

[0641] General_screening_panel_v1.4 Summary: Ag4227 Expression of this gene is restricted to the testis (CT=33.5) and fetal lung (CT=34.7). Thus, expression of this gene could be used to differentiate between these samples and the other samples on this panel and as a marker of testicular tissue. In addition, therapeutic modulation of the expression or function of this gene may be useful in the treatment of male infertility and hypogonadism.

F. CG102092-01: GRP1-Associated Scaffold Protein GRASP

[0642] Expression of gene CG102092-01 was assessed using the primer-probe set Ag4231, described in Table FA. Results of the RTQ-PCR runs are shown in Tables FB, FC, FD, FE and FF.

TABLE FA
Probe Name Ag4231
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-atcaattcggaaggcagaac-3′	20	630	104
Probe	TET-5′-cgtctgcagtacctgaagcaaaccct-3′-TAMRA	26	658	105
Reverse	5′-acctgtactctccccacttctc-3′	22	688	106

[0643]

TABLE FB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4231, Run		Ag4231, Run
Tissue Name	224078129	Tissue Name	224078129
AD 1 Hippo	7.7	Control (Path) 3	7.0
		Temporal Ctx
AD 2 Hippo	21.0	Control (Path) 4	30.8
		Temporal Ctx
AD 3 Hippo	4.6	AD 1 Occipital Ctx	6.7
AD 4 Hippo	23.0	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 hippo	57.4	AD 3 Occipital Ctx	6.7
AD 6 Hippo	27.5	AD 4 Occipital Ctx	26.1
Control 2 Hippo	26.6	AD 5 Occipital Ctx	48.0
Control 4 Hippo	10.2	AD 6 Occipital Ctx	48.0
Control (Path) 3 Hippo	5.6	Control 1 Occipital Ctx	12.9
AD 1 Temporal Ctx	11.8	Control 2 Occipital Ctx	75.3
AD 2 Temporal Ctx	29.1	Control 3 Occipital Ctx	21.3
AD 3 Temporal Ctx	9.5	Control 4 Occipital Ctx	7.5
AD 4 Temporal Ctx	33.4	Control (Path) 1	100.0
		Occipital Ctx
AD 5 Inf Temporal Ctx	62.4	Control (Path) 2	14.0
		Occipital Ctx
AD 5 Sup Temporal Ctx	27.4	Control (Path) 3	11.6
		Occipital Ctx
AD 6 Inf Temporal Ctx	32.1	Control (Path) 4	14.2
		Occipital Ctx
AD 6 Sup Temporal Ctx	34.6	Control 1 Parietal Ctx	7.7
Control 1 Temporal Ctx	8.4	Control 2 Parietal Ctx	39.0
Control 2 Temporal Ctx	55.9	Control 3 Parietal Ctx	17.7
Control 3 Temporal Ctx	22.8	Control (Path) 1 Parietal	92.7
		Ctx
Control 4 Temporal Ctx	11.4	Control (Path) 2 Parietal	23.0
		Ctx
Control (Path) 1 Temporal	87.7	Control (Path) 3 Parietal	12.8
Ctx		Ctx
Control (Path) 2 Temporal	54.0	Control (Path) 4 Parietal	50.3
Ctx		Ctx

[0644]

TABLE FC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4231,		Ag4231, Run
Tissue Name	Run 221994366	Tissue Name	221994366
Adipose	48.6	Renal ca. TK-10	1.3
Melanoma* Hs688(A).T	3.3	Bladder	9.3
Melanoma* Hs688(B).T	1.0	Gastric ca. (liver met.)	0.7
		NCI-N87
Melanoma* M14	13.4	Gastric ca. KATO III	0.4
Melanoma* LOXIMVI	0.2	Colon ca. SW-948	0.5
Melanoma* SK-MEL-5	15.1	Colon ca. SW480	0.7
Squamous cell carcinoma	0.3	Colon ca.* (SW480 met)	1.1
SCC-4		SW620
Testis Pool	2.5	Colon ca. HT29	0.0
Prostate ca.* (bone met)	0.4	Colon ca. HCT-116	0.7
PC-3
Prostate Pool	6.0	Colon ca. CaCo-2	1.9
Placenta	7.4	Colon cancer tissue	12.8
Uterus Pool	2.9	Colon ca. SW1116	0.2
Ovarian ca. OVCAR-3	0.7	Colon ca. Colo-205	0.3
Ovarian ca. SK-OV-3	3.5	Colon ca. SW-48	0.2
Ovarian ca. OVCAR-4	1.2	Colon Pool	7.4
Ovarian ca. OVCAR-5	0.6	Small Intestine Pool	9.2
Ovarian ca. IGROV-1	4.7	Stomach Pool	5.8
Ovarian ca. OVCAR-8	2.3	Bone Marrow Pool	2.9
Ovary	5.6	Fetal Heart	3.3
Breast ca. MCF-7	0.5	Heart Pool	3.8
Breast ca. MDA-MB-231	0.4	Lymph Node Pool	7.6
Breast ca. BT 549	0.4	Fetal Skeletal Muscle	4.6
Breast ca. T47D	1.7	Skeletal Muscle Pool	8.0
Breast ca. MDA-N	0.4	Spleen Pool	16.0
Breast Pool	10.4	Thymus Pool	5.9
Trachea	5.9	CNS cancer (glio/astro)	2.5
		U87-MG
Lung	1.4	CNS cancer (glio/astro)	0.8
		U-118-MG
Fetal Lung	69.3	CNS cancer (neuro; met)	15.6
		SK-N-AS
Lung ca. NCI-N417	0.1	CNS cancer (astro) SF-	5.5
		539
Lung ca. LX-1	0.9	CNS cancer (astro)	4.5
		SNB-75
Lung ca. NCI-H146	3.6	CNS cancer (glio) SNB-	4.0
		19
Lung ca. SHP-77	5.5	CNS cancer (glio) SF-	1.3
		295
Lung ca. A549	0.7	Brain (Amygdala) Pool	14.2
Lung ca. NCI-H526	100.0	Brain (cerebellum)	2.6
Lung ca. NCI-H23	2.8	Brain (fetal)	5.4
Lung ca. NCI-H460	0.4	Brain (Hippocampus)	9.0
		Pool
Lung ca. HOP-62	0.2	Cerebral Cortex Pool	16.3
Lung ca. NCI-H522	1.2	Brain (Substantia nigra)	21.6
		Pool
Liver	0.6	Brain (Thalamus) Pool	20.3
Fetal Liver	1.9	Brain (whole)	22.7
Liver ca. HepG2	6.3	Spinal Cord Pool	3.0
Kidney Pool	18.2	Adrenal Gland	4.9
Fetal Kidney	6.0	Pituitary gland Pool	0.4
Renal ca. 786-0	0.6	Salivary Gland	0.8
Renal ca. A498	0.2	Thyroid (female)	6.6
Renal ca. ACHN	0.4	Pancreatic ca. CAPAN2	0.4
Renal ca. UO-31	0.2	Pancreas Pool	7.8

[0645]

TABLE FD
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4231, Run		Ag4231, Run
Tissue Name	175226629	Tissue Name	175226629
Secondary Th1 act	0.1	HUVEC IL-1beta	14.0
Secondary Th2 act	0.4	HUVEC IFN gamma	14.6
Secondary Tr1 act	0.2	HUVEC TNF alpha +	4.0
		IFN gamma
Secondary Th1 rest	0.1	HUVEC TNF alpha +	8.8
		IL4
Secondary Th2 rest	0.4	HUVEC IL-11	10.2
Secondary Tr1 rest	0.2	Lung Microvascular EC	18.0
		none
Primary Th1 act	1.0	Lung Microvascular EC	19.1
		TNF alpha + IL-1beta
Primary Th2 act	1.2	Microvascular Dermal	6.9
		EC none
Primary Tr1 act	2.2	Microsvasular Dermal	10.1
		EC TNF alpha + IL-1beta
Primary Th1 rest	1.2	Bronchial epithelium	0.1
		TNF alpha + IL1beta
Primary Th2 rest	1.1	Small airway epithelium	0.0
		none
Primary Tr1 rest	0.9	Small airway epithelium	0.0
		TNF alpha + IL-1beta
CD45RA CD4 lymphocyte	100.0	Coronery artery SMC	1.0
act		rest
CD45RO CD4 lymphocyte	1.6	Coronery artery SMC	1.3
act		TNF alpha + IL-1beta
CD8 lymphocyte act	1.3	Astrocytes rest	0.0
Secondary CD8	1.1	Astrocytes TNF alpha +	0.3
lymphocyte rest		IL-1beta
Secondary CD8	0.2	KU-812 (Basophil) rest	0.4
lymphocyte act
CD4 lymphocyte none	0.6	KU-812 (Basophil)	0.5
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	0.6	CCD1106	0.1
CD95 CH11		(Keratinocytes) none
LAK cells rest	2.7	CCD1106	0.2
		(Keratinocytes)
		TNF alpha + IL-1beta
LAK cells IL-2	0.4	Liver cirrhosis	1.8
LAK cells IL-2 + IL-12	0.7	NCI-H292 none	0.1
LAK cells IL-2 + IFN	0.4	NCI-H292 IL-4	0.1
gamma
LAK cells IL-2 + IL-18	0.9	NCI-H292 IL-9	0.2
LAK cells PMA/ionomycin	15.3	NCI-H292 IL-13	0.1
NK Cells IL-2 rest	1.0	NCI-H292 IFN gamma	0.1
Two Way MLR 3 day	0.9	HPAEC none	13.3
Two Way MLR 5 day	1.8	HPAEC TNF alpha +	19.2
		IL-1beta
Two Way MLR 7 day	1.7	Lung fibroblast none	2.6
PBMC rest	1.4	Lung fibroblast TNF	0.7
		alpha + IL-1beta
PBMC PWM	0.7	Lung fibroblast IL-4	1.9
PBMC PHA-L	1.2	Lung fibroblast IL-9	1.4
Ramos (B cell) none	0.0	Lung fibroblast IL-13	1.5
Ramos (B cell) ionomycin	0.0	Lung fibroblast IFN	1.1
		gamma
B lymphocytes PWM	0.6	Dermal fibroblast	0.3
		CCD1070 rest
B lymphocytes CD40L and	0.7	Dermal fibroblast	0.3
IL-4		CCD1070 TNF alpha
EOL-1 dbcAMP	0.1	Dermal fibroblast	0.2
		CCD1070 IL-1beta
EOL-1 dbcAMP	0.3	Dermal fibroblast IFN	1.1
PMA/ionomycin		gamma
Dendritic cells none	0.6	Dermal fibroblast IL-4	1.7
Dendritic cells LPS	3.5	Dermal Fibroblasts rest	2.0
Dendritic cells anti-CD40	1.0	Neutrophils TNFa + LPS	1.0
Monocytes rest	0.6	Neutrophils rest	0.3
Monocytes LPS	2.0	Colon	1.0
Macrophages rest	2.0	Lung	3.9
Macrophages LPS	5.9	Thymus	4.9
HUVEC none	9.6	Kidney	1.9
HUVEC starved	16.7

[0646]

TABLE FE
Panel CNS_1
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4231,		Ag4231,
Tissue Name	Run 181012262	Tissue Name	Run 181012262
BA4 Control	25.2	BA17 PSP	22.5
BA4 Control2	71.2	BA17 PSP2	15.9
BA4 Alzheimer's2	5.8	Sub Nigra Control	6.0
BA4 Parkinson's	66.0	Sub Nigra Control2	4.3
BA4 Parkinson's2	55.1	Sub Nigra Alzheimer's2	4.9
BA4 Huntington's	27.7	Sub Nigra Parkinson's2	12.5
BA4 Huntington's2	29.7	Sub Nigra Huntington's	58.2
BA4 PSP	10.3	Sub Nigra Huntington's2	22.1
BA4 PSP2	14.8	Sub Nigra PSP2	3.0
BA4 Depression	11.7	Sub Nigra Depression	8.2
BA4 Depression2	6.9	Sub Nigra Depression2	7.9
BA7 Control	27.9	Glob Palladus Control	10.2
BA7 Control2	43.8	Glob Palladus Control2	23.7
BA7 Alzheimer's2	7.7	Glob Palladus	9.9
		Alzheimer's
BA7 Parkinson's	22.5	Glob Palladus	4.0
		Alzheimer's2
BA7 Parkinson's2	44.8	Glob Palladus	95.9
		Parkinson's
BA7 Huntington's	37.9	Glob Palladus	16.5
		Parkinson's2
BA7 Huntington's2	30.1	Glob Palladus PSP	0.0
BA7 PSP	25.5	Glob Palladus PSP2	3.7
BA7 PSP2	30.6	Glob Palladus	0.7
		Depression
BA7 Depression	4.2	Temp Pole Control	18.9
BA9 Control	31.9	Temp Pole Control2	52.1
BA9 Control2	100.0	Temp Pole Alzheimer's	7.3
BA9 Alzheimer's	7.3	Temp Pole Alzheimer's2	7.9
BA9 Alzheimer's2	19.9	Temp Pole Parkinson's	42.3
BA9 Parkinson's	33.9	Temp Pole Parkinson's2	50.0
BA9 Parkinson's2	59.0	Temp Pole Huntington's	43.8
BA9 Huntington's	64.6	Temp Pole PSP	1.4
BA9 Huntington's2	22.1	Temp Pole PSP2	14.0
BA9 PSP	5.1	Temp Pole Depression2	13.1
BA9 PSP2	0.6	Cing Gyr Control	52.5
BA9 Depression	12.1	Cing Gyr Control2	57.4
BA9 Depression2	16.8	Cing Gyr Alzheimer's	31.2
BA17 Control	23.8	Cing Gyr Alzheimer's2	14.1
BA17 Control2	34.2	Cing Gyr Parkinson's	22.5
BA17 Alzheimer's2	11.0	Cing Gyr Parkinson's2	26.1
BA17 Parkinson's	28.7	Cing Gyr Huntington's	60.7
BA17 Parkinson's2	39.5	Cing Gyr Huntington's2	14.6
BA17 Huntington's	57.8	Cing Gyr PSP	8.5
BA17 Huntington's2	27.5	Cing Gyr PSP2	5.3
BA17 Depression	12.5	Cing Gyr Depression	9.8
BA17 Depression2	24.8	Cing Gyr Depression2	7.3

[0647]

TABLE FF
general oncology screening panel_v_2.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4231, Run		Ag4231, Run
Tissue Name	268624976	Tissue Name	268624976
Colon cancer 1	15.0	Bladder cancer NAT 2	0.0
Colon NAT 1	12.8	Bladder cancer NAT 3	0.5
Colon cancer 2	4.4	Bladder cancer NAT 4	7.0
Colon cancer NAT 2	5.1	Adenocarcinoma of the	13.8
		prostate 1
Colon cancer 3	12.6	Adenocarcinoma of the	8.4
		prostate 2
Colon cancer NAT 3	11.6	Adenocarcinoma of the	8.4
		prostate 3
Colon malignant cancer 4	15.3	Adenocarcinoma of the	6.4
		prostate 4
Colon normal adjacent	2.3	Prostate cancer NAT 5	5.0
tissue 4
Lung cancer 1	13.7	Adenocarcinoma of the	3.3
		prostate 6
Lung NAT 1	5.3	Adenocarcinoma of the	6.2
		prostate 7
Lung cancer 2	39.0	Adenocarcinoma of the	0.9
		prostate 8
Lung NAT 2	15.7	Adenocarcinoma of the	18.0
		prostate 9
Squamous cell carcinoma 3	28.9	Prostate cancer NAT 10	2.3
Lung NAT 3	5.2	Kidney cancer 1	63.3
metastatic melanoma 1	40.1	KidneyNAT 1	22.7
Melanoma 2	9.9	Kidney cancer 2	100.0
Melanoma 3	3.5	Kidney NAT 2	21.3
metastatic melanoma 4	25.9	Kidney cancer 3	26.6
metastatic melanoma 5	29.5	Kidney NAT 3	12.8
Bladder cancer 1	0.7	Kidney cancer 4	49.0
Bladder cancer NAT 1	0.0	Kidney NAT 4	26.6
Bladder cancer 2	1.1

[0648] CNS_neurodegeneration_v1.0 Summary: Ag4231 This panel confirms the expression of the CG102092-01 gene at significant levels in the brain in an independent group of individuals. This gene is found to be down-regulated in the temporal cortex of Alzheimer's disease patients when analyzed by ANCOVA (P=0.04). Treatment with agonists or antagonists may therefore prevent or delay the onset of AD.

[0649] General_screening_panel_v1.4 Summary: Ag4231 Highest expression of the CG102092-01 gene is detected in lung cancer NCI-H526 cell line (CT=25). Significant expression of this gene is also seen in cluster of cancer cell lines derived from gastric, colon, lung, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers. Thus, therapeutic modulation of the expression or function of this gene may be effective in the treatment of gastric, colon, lung, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers.

[0650] 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. This gene codes for a homolog of mouse GRP1-associated scaffold protein GRASP, also known as tamalin. GRASP links a protein complex formation of group 1 metabotropic glutamate receptors (mGluRs) and the guanine nucleotide exchange factor, cytohesins. In addition, it contributes to intracellular trafficking and the macromolecular organization of group 1 mGluRs at synapses (Kitano et al., 2002, J Neurosci 22(4):1280-9, PMID: 11850456; Nevrivy et al., 2000, J Biol Chem 275(22):16827-36, PMID: 10828067). Group I mGluRs are involved in many CNS functions and may participate in a variety of disorders such as pain, epilepsy, ischemia, and chronic neurodegenerative diseases (Bordi F, Ugolini A., 1999, Prog Neurobiol 59(1):55-79, PMID: 10416961). Therefore, therapeutic modulation of this gene product may be useful in the treatment of neurological disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia, pain, ischemia and depression.

[0651] Among tissues with metabolic or endocrine function, this gene is expressed at 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.

[0652] Panel 4.1D Summary: Ag4231 Highest expression of the CG102092-01 gene is detected in activated CD45RA CD4 lymphocyte (CT=26.8). This gene is expressed at moderate to low 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 lung fibroblast cell types 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.

[0653] Panel CNS—1 Summary: Ag4231 This panel confirms the expression of the CG102092-01 gene at significant levels in the brain in an independent group of individuals. Please see Panel 1.4 for a discussion of this gene in treatment of central nervous system disorders.

[0654] General oncology screening panel_v—2.4 Summary: Ag4231 Highest expression of the CG102092-01 gene is detected in kidney cancer sample (CT=30.3). Significant levels of expression of this gene is also seen in both normal and cancer samples derived from colon, lung, melanoma, prostate, and kidney. Thus, therapeutic modulation of the expression or function of this gene may be effective in the treatment of colon, lung, prostate, melanoma and kidney cancers.

G. CG102595-01: neurabin-I (Neural Tissue-specific F-actin Binding Protein I)

[0655] Expression of gene CG102595-01 was assessed using the primer-probe set Ag4239, described in Table GA. Results of the RTQ-PCR runs are shown in Tables GB, GC, GD, GE and GF.

TABLE GA
Probe Name Ag4239
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-caagcgaggtgttgatacaga-3′	21	846	107
Probe	TET-5′-tgcaactccagtaccagaagtggctt-3′-TAMRA	26	885	108
Reverse	5′-ttcaccaggtatcgaagctaga-3′	22	924	109

[0656]

TABLE GB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4239, Run		Ag4239, Run
Tissue Name	224076987	Tissue Name	224076987
AD 1 Hippo	18.9	Control (Path) 3 Temporal	4.2
		Ctx
AD 2 Hippo	27.2	Control (Path) 4 Temporal	32.1
		Ctx
AD 3 Hippo	5.3	AD 1 Occipital Ctx	22.4
AD 4 Hippo	8.3	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 Hippo	95.3	AD 3 Occipital Ctx	6.1
AD 6 Hippo	46.0	AD 4 Occipital Ctx	22.4
Control 2 Hippo	32.3	AD 5 Occipital Ctx	47.3
Control 4 Hippo	13.4	AD 6 Occipital Ctx	26.1
Control (Path) 3 Hippo	6.7	Control 1 Occipital Ctx	2.3
AD 1 Temporal Ctx	15.4	Control 2 Occipital Ctx	67.8
AD 2 Temporal Ctx	31.2	Control 3 Occipital Ctx	19.8
AD 3 Temporal Ctx	7.0	Control 4 Occipital Ctx	6.7
AD 4 Temporal Ctx	25.5	Control (Path) 1 Occipital	93.3
		Ctx
AD 5 Inf Temporal Ctx	100.0	Control (Path) 2 Occipital	17.3
		Ctx
AD 5 Sup Temporal Ctx	46.0	Control (Path) 3 Occipital	2.0
		Ctx
AD 6 Inf Temporal Ctx	46.3	Control (Path) 4 Occipital	17.0
		Ctx
AD 6 Sup Temporal Ctx	45.7	Control 1 Parietal Ctx	6.7
Control 1 Temporal Ctx	5.4	Control 2 Parietal Ctx	44.4
Control 2 Temporal Ctx	41.8	Control 3 Parietal Ctx	24.5
Control 3 Temporal Ctx	15.5	Control (Path) 1 Parietal	84.1
		Ctx
Control 3 Temporal Ctx	11.5	Control (Path) 2 Parietal	25.5
		Ctx
Control (Path) 1 Temporal	58.6	Control (Path) 3 Parietal	3.1
Ctx		Ctx
Control (Path) 2 Temporal	36.6	Control (Path) 4 Parietal	46.7
Ctx		Ctx

[0657]

TABLE GC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4239, Run		Ag4239, Run
Tissue Name	222026936	Tissue Name	222026936
Adipose	8.7	Renal ca. TK-10	76.8
Melanoma* Hs688(A).T	0.0	Bladder	42.9
Melanoma* Hs688(B).T	0.0	Gastric ca. (liver met.) NCI-	0.2
		N87
Melanoma* M14	0.0	Gastric ca. KATO III	0.0
Melanoma* LOXIMVI	2.2	Colon ca. SW-948	11.5
Melanoma* SK-MEL-5	48.6	Colon ca. SW480	71.2
Squamous cell carcinoma	0.0	Colon ca.* (SW480 met)	24.7
SCC-4		SW620
Testis Pool	23.8	Colon ca. HT29	15.0
Prostate ca.* (bone met)	65.5	Colon ca. HCT-116	44.1
PC-3
Prostate Pool	13.2	Colon ca. CaCo-2	100.0
Placenta	3.8	Colon cancer tissue	2.0
Uterus Pool	7.9	Colon ca. SW1116	8.9
Ovarian ca. OVCAR-3	50.3	Colon ca. Colo-205	0.1
Ovarian ca. SK-OV-3	35.4	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	28.5	Colon Pool	13.2
Ovarian ca. OVCAR-5	49.0	Small Intestine Pool	23.7
Ovarian ca. IGROV-1	47.0	Stomach Pool	24.0
Ovarian ca. OVCAR-8	11.0	Bone Marrow Pool	5.9
Ovary	15.7	Fetal Heart	36.6
Breast ca. MCF-7	7.1	Heart Pool	9.0
Breast ca. MDA-MB-231	7.2	Lymph Node Pool	27.4
Breast ca. BT 549	66.0	Fetal Skeletal Muscle	29.3
Breast ca. T47D	63.3	Skeletal Muscle Pool	22.7
Breast ca. MDA-N	0.1	Spleen Pool	25.3
Breast Pool	19.6	Thymus pool	13.5
Trachea	29.5	CNS cancer (glio/astro)	2.2
		U87-MG
Lung	11.2	CNS cancer (glio/astro) U-	0.1
		118-MG
Fetal Lung	77.9	CNS cancer (neuro; met)	20.9
		SK-N-AS
Lung ca. NCI-N417	2.5	CNS cancer (astro) SF-539	0.7
Lung ca. LX-1	55.5	CNS cancer (astro) SNB-75	1.0
Lung ca. NCI-H146	6.7	CNS cancer (glio) SNB-19	57.4
Lung ca. SHP-77	28.3	CNS cancer (glio) SF-295	4.3
Lung ca. A549	74.2	Brain (Amygdala) Pool	40.1
Lung ca. NCI-H526	9.0	Brain (cerebellum)	23.0
Lung ca. NCI-H23	53.6	Brain (fetal)	73.2
Lung ca. NCI-H460	14.7	Brain (Hippocampus) Pool	40.6
Lung ca. HOP-62	7.4	Cerebral Cortex Pool	80.7
Lung ca. NCI-H522	11.0	Brain (Substantia nigra)	53.2
		Pool
Liver	0.0	Brain (Thalamus) Pool	75.3
Fetal Liver	17.2	Brain (whole)	38.7
Liver ca. HepG2	51.1	Spinal Cord Pool	28.9
Kidney Pool	32.1	Adrenal Gland	28.5
Fetal Kidney	84.1	Pituitary gland Pool	16.7
Renal ca. 786-0	43.2	Salivary Gland	14.3
Renal ca. A498	14.2	Thyroid (female)	9.3
Renal ca. ACHN	9.9	Pancreatic ca. CAPAN2	45.1
Renal ca. UO-31	55.5	Pancreas Pool	36.3

[0658]

TABLE GD
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4239, Run		Ag4239, Run
Tissue Name	175226819	Tissue Name	175226819
Secondary Th1 act	1.2	HUVEC IL-1beta	9.9
Secondary Th2 act	0.4	HUVEC IFN gamma	11.3
Secondary Tr1 act	0.0	HUVEC TNF alpha + IFN	3.0
		gamma
Secondary Th1 rest	0.2	HUVEC TNF alpha + IL4	5.5
Secondary Th2 rest	0.0	HUVEC IL-11	9.7
Secondary Tr1 rest	0.3	Lung Microvascular EC	3.9
		none
Primary Th1 act	0.8	Lung Microvascular EC	0.4
		TNF alpha + IL-1beta
Primary Th2 act	0.0	Microvascular Dermal EC	5.0
		none
Primary Tr1 act	0.0	Microsvasular Dermal EC	1.6
		TNF alpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium	0.0
		TNF alpha + IL1beta
Primary Th2 rest	0.0	Small airway epithelium	0.6
		none
Primary Tr1 rest	0.0	Small airway epithelium	0.0
		TNF alpha + IL-1beta
CD45RA CD4 lymphocyte	2.0	Coronery artery SMC rest	0.0
act
CD45RO CD4 lymphocyte	0.0	Coronery artery SMC	0.9
act		TNF alpha + IL-1beta
CD8 lymphocyte act	0.3	Astrocytes rest	22.2
Secondary CD8 lymphocyte	0.0	Astrocytes TNF alpha + IL-	19.5
rest		1beta
Secondary CD8 lymphocyte	0.0	KU-812 (Basophil) rest	7.3
act
CD4 lymphocyte none	0.5	KU-812 (Basophil)	9.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	0.0	CCD1106 (Keratinocytes)	0.0
CD95 CH11		none
LAK cells rest	4.0	CCD1106 (Keratinocytes)	0.0
		TNF alpha + IL-1beta
LAK cells IL-2	2.5	Liver cirrhosis	13.3
LAK cells IL-2 + IL-12	1.8	NCI-H292 none	13.1
LAK cells IL-2 + IFN	1.7	NCI-H292 IL-4	21.6
gamma
LAK cells IL-2 + IL-18	2.1	NCI-H292 IL-9	24.0
LAK cells PMA/ionomycin	1.7	NCI-H292 IL-13	24.0
NK Cells IL-2 rest	18.0	NCI-H292 IFN gamma	19.2
Two Way MLR 3 day	1.2	HPAEC none	14.2
Two Way MLR 5 day	0.4	HPAEC TNF alpha + IL-1	15.7
		beta
Two Way MLR 7 day	0.0	Lung fibroblast none	6.6
PBMC rest	0.5	Lung fibroblast TNF alpha +	3.5
		IL-1beta
PBMC PWM	3.2	Lung fibroblast IL-4	4.6
PBMC PHA-L	0.7	Lung fibroblast IL-9	9.2
Ramos (B cell) none	0.0	Lung fibroblast IL-13	5.8
Ramos (B cell) ionomycin	0.0	Lung fibroblast IFN gamma	5.7
B lymphocytes PWM	3.2	Dermal fibroblast CCD1070	3.5
		rest
B lymphocytes CD40L and	2.1	Dermal fibroblast CCD1070	2.5
IL-4		TNF alpha
EOL-1 dbcAMP	0.0	Dermal fibroblast CCD1070	1.3
		IL-1beta
EOL-1 dbcAMP	0.0	Dermal fibroblast IFN	2.2
PMA/ionomycin		gamma
Dendritic cells none	0.9	Dermal fibroblast IL-4	12.9
Dendritic cells LPS	0.5	Dermal Fibroblasts rest	9.7
Dendritic cells anti-CD40	0.0	Neutrophils TNFa + LPS	1.0
Monocytes rest	0.5	Neutrophils rest	2.3
Monocytes LPS	0.0	Colon	15.4
Macrophages rest	1.1	Lung	19.3
Macrophages LPS	0.0	Thymus	12.8
HUVEC none	4.1	Kidney	100.0
HUVEC starved	7.2

[0659]

TABLE GE
Panel CNS_1
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4239,		Ag4239, Run
Tissue Name	Run 181012675	Tissue Name	181012675
BA4 Control	36.6	BA17 PSP	18.4
BA4 Control2	49.7	BA17 PSP2	11.3
BA4 Alzheimer's2	8.0	Sub Nigra Control	31.6
BA4 Parkinson's	59.5	Sub Nigra Control2	25.3
BA4 Parkinson's2	100.0	Sub Nigra Alzheimer's2	9.0
BA4 Huntington's	32.3	Sub Nigra Parkinson's2	43.5
BA4 Huntington's2	4.4	Sub Nigra Huntington's	46.0
BA4 PSP	11.5	Sub Nigra Huntington's2	24.5
BA4 PSP2	29.3	Sub Nigra PSP2	6.8
BA4 Depression	12.6	Sub Nigra Depression	7.5
BA4 Depression2	8.0	Sub Nigra Depression2	4.6
BA7 Control	49.3	Glob Palladus Control	15.5
BA7 Control2	34.6	Glob Palladus Control2	14.0
BA7 Alzheimer's2	3.6	Glob Palladus Alzheimer's	8.8
BA7 Parkinson's	17.6	Glob Palladus Alzheimer's2	3.8
BA7 Parkinson's2	54.3	Glob Palladus Parkinson's	84.1
BA7 Huntington's	52.1	Glob Palladus Parkinson's2	18.2
BA7 Huntington's2	62.0	Glob Palladus PSP	4.7
BA7 PSP	27.4	Glob Palladus PSP2	8.5
BA7 PSP2	28.5	Glob Palladus Depression	5.8
BA7 Depression	9.0	Temp Pole Control	15.8
BA9 Control	27.4	Temp Pole Control2	41.2
BA9 Control2	74.2	Temp Pole Alzheimer's	6.0
BA9 Alzheimer's	5.2	Temp Pole Alzheimer's2	5.3
BA9 Alzheimer's2	13.1	Temp Pole Parkinson's	27.7
BA9 Parkinson's	31.4	Temp Pole Parkinson's2	29.3
BA9 Parkinson's2	49.0	Temp Pole Huntington's	39.5
BA9 Huntington's	53.2	Temp Pole PSP	2.3
BA9 Huntington's2	23.7	Temp Pole PSP2	4.6
BA9 PSP	12.0	Temp Pole Depression2	7.3
BA9 PSP2	3.8	Cing Gyr Control	63.3
BA9 Depression	4.7	Cing Gyr Control2	35.4
BA9 Depression2	6.5	Cing Gyr Alzheimer's	19.9
BA17 Control	64.2	Cing Gyr Alzheimer's2	9.1
BA17 Control2	47.6	Cing Gyr Parkinson's	35.6
BA17 Alzheimer's2	9.9	Cing Gyr Parkinson's2	37.1
BA17 Parkinson's	36.3	Cing Gyr Huntington's	72.2
BA17 Parkinson's2	57.4	Cing Gyr Huntington's2	27.5
BA17 Huntington's	33.9	Cing Gyr PSP	15.8
BA17 Huntington's2	22.2	Cing Gyr PSP2	4.9
BA17 Depression	8.4	Cing Gyr Depression	7.1
BA17 Depression2	25.5	Cing Gyr Depression2	9.5

[0660]

TABLE GF
general oncology screening panel_v_2.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4239, Run		Ag4239, Run
Tissue Name	268664315	Tissue Name	268664315
Colon cancer 1	5.1	Bladder cancer NAT 2	0.2
Colon NAT 1	6.3	Bladder cancer NAT 3	0.2
Colon cancer 2	8.3	Bladder cancer NAT 4	3.5
Colon cancer NAT 2	4.0	Adenocarcinoma of the	2.2
		prostate 1
Colon cancer 3	2.8	Adenocarcinoma of the	1.2
		prostate 2
Colon cancer NAT 3	18.4	Adenocarcinoma of the	4.0
		prostate 3
Colon malignant cancer 4	17.3	Adenocarcinoma of the	5.8
		prostate 4
Colon normal adjacent	3.4	Prostate cancer NAT 5	0.4
tissue 4
Lung cancer 1	23.8	Adenocarcinoma of the	2.5
		prostate 6
Lung NAT 1	1.6	Adenocarcinoma of the	2.7
		prostate 7
Lung cancer 2	100.0	Adenocarcinoma of the	1.3
		prostate 8
Lung NAT 2	2.0	Adenocarcinoma of the	3.8
		prostate 9
Squamous cell carcinoma 3	17.3	Prostate cancer NAT 10	1.7
Lung NAT 3	0.8	Kidney cancer 1	8.2
metastatic melanoma 1	14.9	KidneyNAT 1	8.7
Melanoma 2	0.2	Kidney cancer 2	33.7
Melanoma 3	1.2	Kidney NAT 2	20.6
metastatic melanoma 4	22.5	Kidney cancer 3	11.0
metastatic melanoma 5	21.5	Kidney NAT 3	6.9
Bladder cancer 1	0.8	Kidney cancer 4	5.0
Bladder cancer NAT 1	0.0	Kidney NAT 4	4.5
Bladder cancer 2	1.8

[0661] CNS_neurodegeneration_v1.0 Summary: Ag4239 This panel confirms the presence of this gene in the brain. Please see Panel 1.4 for discussion of this gene in the central nervous system.

[0662] General_screening panel_v1.4 Summary: Ag4239 This gene is widely expressed in this panel, with highest expression in a colon cancer cell line (CT=26.6). High levels of expression are also seen in cell lines derived from brain, renal, prostate, lung, breast, ovarian, and melanoma cancers. In addition, higher levels of expression are seen in fetal liver (CT=29) and lung (CT=26.9) when compared to expression in the adult liver (CT=40) and lung (CT=29.7). Thus, expression of this gene could be used to differentiate between the fetal and adult sources of these tissues. Since cell lines and fetal tissues are generally more proliferative than adult tissue, this expression profile suggests a role for this gene product in cell survival and proliferation. Therefore, modulation of this gene product may be useful in the treatment of cancer.

[0663] Among tissues with metabolic function, this gene is expressed at moderate levels in pituitary, adipose, adrenal gland, pancreas, thyroid, fetal liver and adult and fetal skeletal muscle and heart. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0664] This gene is also expressed at high levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. This gene encodes a homolog of neurabin, a neural protein that may be involved in neurite formation. 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.

[0665] Panel 4.1D Summary: Ag4239 Highest expression of this gene is seen in kidney (CT=29. 7). In addition, this gene is expressed at low but significant levels in a wide range of cell types of significance in the immune response in health and disease. These cells include LAK and NK 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_v1.4 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.

[0666] Panel CNS—1 Summary: Ag4239 This panel confirms the presence of this gene in the brain. Please see Panel 1.4 for discussion of this gene in the central nervous system.

[0667] General oncology screening panel_v—2.4 Summary: Ag4239 Highest expression of this gene is seen in lung cancer (CT=26.7). In addition, this gene appears to be overexpressed in lung and kidney cancer when compared to expression in normal adjacent tissue. Furthermore, significant expression of this gene is also seen in melanoma, prostate, bladder and colon cancer. Therefore, therapeutic, modulation of this gene product may be useful in the treatment of these cancers.

H. CG102744-01: Novel Epidermal Fatty Acid Receptor

[0668] Expression of gene CG102744-01 was assessed using the primer-probe set Ag4252, described in Table HA.

TABLE HA
Probe Name Ag4252
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ggactgtgtcatgaaccatgt-3′	21	357	110
Probe	TET-5′-cgcctgtactcggatctatgaaaa-3′-TAMRA	24	378	111
Reverse	5′-ctgtccaaagtgatgatggaa-3′	21	415	112

I. CG102801-01: Septin 6-like Protein

[0669] Expression of gene CG102801-01 was assessed using the primer-probe set Ag4243, described in Table IA. Results of the RTQ-PCR runs are shown in Tables IB, IC, ID, IE and IF.

TABLE IA
Probe Name Ag4243
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gtagaaacaaaccaacgaccaa-3′	22	3452	113
Probe	TET-5′-tgctcagatactcagccagtagctca-3′-TAMRA	26	496	114
Reverse	5′-agacctgacaggcctaactca-3′	21	3531	115

[0670]

TABLE IB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4243, Run		Ag4243, Run
Tissue Name	224077466	Tissue Name	224077466
AD 1 Hippo	17.8	Control (Path) 3 Temporal	13.7
		Ctx
AD 2 Hippo	29.5	Control (Path) 4 Temporal	38.2
		Ctx
AD 3 Hippo	17.7	AD 1 Occipital Ctx	32.1
AD 4 Hippo	6.3	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 Hippo	100.0	AD 3 Occipital Ctx	15.0
AD 6 Hippo	63.7	AD 4 Occipital Ctx	27.5
Control 2 Hippo	30.6	AD 5 Occipital Ctx	38.4
Control 4 Hippo	21.6	AD 6 Occipital Ctx	28.9
Control (Path) 3 Hippo	20.6	Control 1 Occipital Ctx	21.3
AD 1 Temporal Ctx	32.3	Control 2 Occipital Ctx	50.3
AD 2 Temporal Ctx	35.6	Control 3 Occipital Ctx	28.3
AD 3 Temporal Ctx	14.9	Control 4 Occipital Ctx	6.3
AD 4 Temporal Ctx	33.9	Control (Path) 1 Occipital	79.0
		Ctx
AD 5 Inf Temporal Ctx	71.2	Control (Path) 2 Occipital	25.5
		Ctx
AD 5 Sup Temporal Ctx	47.0	Control (Path) 3 Occipital	5.1
		Ctx
AD 6 Inf Temporal Ctx	71.2	Control (Path) 4 Occipital	36.6
		Ctx
AD 6 Sup Temporal Ctx	79.0	Control 1 Parietal Ctx	21.0
Control 1 Temporal Ctx	13.8	Control 2 Parietal Ctx	55.1
Control 2 Temporal Ctx	26.1	Control 3 Parietal Ctx	22.1
Control 3 Temporal Ctx	31.0	Control (Path) 1 Parietal	55.9
		Ctx
Control 3 Temporal Ctx	17.1	Control (Path) 2 Parietal	51.4
		Ctx
Control (Path) 1 Temporal	55.1	Control (Path) 3 Parietal	12.9
Ctx		Ctx
Control (Path) 2 Temporal	47.6	Control (Path) 4 Parietal	58.2
Ctx		Ctx

[0671]

TABLE IC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4243, Run		Ag4243, Run
Tissue Name	222018642	Tissue Name	222018642
Adipose	7.9	Renal ca. TK-10	2.0
Melanoma* Hs688(A).T	14.1	Bladder	7.0
Melanoma* Hs688(B).T	2.1	Gastric ca. (liver met.)	4.5
		NCI-N87
Melanoma* M14	26.2	Gastric ca. KATO III	5.2
Melanoma* LOXIMVI	10.7	Colon ca. SW-948	0.7
Melanoma* SK-MEL-5	6.3	Colon ca. SW480	12.2
Squamous cell carcinoma	2.4	Colon ca.* (SW480 met)	23.2
SCC-4		SW620
Testis Pool	22.4	Colon ca. HT29	0.3
Prostate ca.* (bone met)	25.5	Colon ca. HCT-116	4.7
PC-3
Prostate Pool	4.2	Colon ca. CaCo-2	8.1
Placenta	4.4	Colon cancer tissue	3.7
Uterus Pool	3.4	Colon ca. SW1116	0.9
Ovarian ca. OVCAR-3	4.8	Colon ca. Colo-205	0.5
Ovarian ca. SK-OV-3	15.2	Colon ca. SW-48	0.8
Ovarian ca. OVCAR-4	1.9	Colon Pool	9.2
Ovarian ca. OVCAR-5	7.3	Small Intestine Pool	15.4
Ovarian ca. IGROV-1	2.8	Stomach Pool	6.5
Ovarian ca. OVCAR-8	6.3	Bone Marrow Pool	6.0
Ovary	3.5	Fetal Heart	4.5
Breast ca. MCF-7	0.2	Heart Pool	4.4
Breast ca. MDA-MB-231	11.3	Lymph Node Pool	9.5
Breast ca. BT 549	50.7	Fetal Skeletal Muscle	7.1
Breast ca. T47D	11.0	Skeletal Muscle Pool	1.2
Breast ca. MDA-N	13.9	Spleen Pool	23.2
Breast Pool	9.2	Thymus Pool	36.3
Trachea	6.4	CNS cancer (glio/astro)	0.7
		U87-MG
Lung	6.9	CNS cancer (glio/astro) U-	1.2
		118-MG
Fetal Lung	32.3	CNS cancer (neuro; met)	100.0
		SK-N-AS
Lung ca. NCI-N417	3.0	CNS cancer (astro) SF-539	11.0
Lung ca. LX-1	7.5	CNS cancer (astro) SNB-75	15.9
Lung ca. NCI-H146	0.1	CNS cancer (glio) SNB-19	2.8
Lung ca. SHP-77	11.4	CNS cancer (glio) SF-295	21.3
Lung ca. A549	6.1	Brain (Amygdala) Pool	0.6
Lung ca. NCI-H526	1.0	Brain (cerebellum)	4.8
Lung ca. NCI-H23	14.6	Brain (fetal)	3.4
Lung ca. NCI-H460	3.3	Brain (Hippocampus) Pool	1.6
Lung ca. HOP-62	7.3	Cerebral Cortex Pool	1.4
Lung ca. NCI-H522	44.8	Brain (Substantia nigra)	1.0
		Pool
Liver	1.2	Brain (Thalamus) Pool	1.5
Fetal Liver	8.2	Brain (whole)	2.0
Liver ca. HepG2	3.8	Spinal Cord Pool	2.1
Kidney Pool	11.3	Adrenal Gland	45.1
Fetal Kidney	40.3	Pituitary gland Pool	1.8
Renal ca. 786-0	2.8	Salivary Gland	2.3
Renal ca. A498	3.7	Thyroid (female)	1.3
Renal ca. ACHN	4.4	Pancreatic ca. CAPAN2	2.4
Renal ca. UO-31	5.4	Pancreas Pool	9.5

[0672]

TABLE ID
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4243, Run		Ag4243, Run
Tissue Name	175165705	Tissue Name	175165705
Secondary Th1 act	35.8	HUVEC IL-1beta	8.1
Secondary Th2 act	32.1	HUVEC IFN gamma	17.4
Secondary Tr1 act	30.6	HUVEC TNF alpha + IFN	7.7
		gamma
Secondary Th1 rest	22.2	HUVEC TNF alpha + IL4	5.2
Secondary Th2 rest	26.4	HUVEC IL-11	9.7
Secondary Tr1 rest	27.9	Lung Microvascular EC	12.9
		none
Primary Th1 act	27.9	Lung Microvascular EC	9.9
		TNF alpha + IL-1beta
Primary Th2 act	36.9	Microvascular Dermal EC	15.6
		none
Primary Tr1 act	36.3	Microsvasular Dermal EC	11.0
		TNF alpha + IL-1beta
Primary Th1 rest	38.4	Bronchial epithelium	1.0
		TNF alpha + IL1beta
Primary Th2 rest	55.9	Small airway epithelium	0.7
		none
Primary Tr1 rest	99.3	Small airway epithelium	0.9
		TNF alpha + IL-1beta
CD45RA CD4 lymphocyte	22.5	Coronery artery SMC rest	7.6
act
CD45RO CD4 lymphocyte	61.1	Coronery artery SMC	7.5
act		TNF alpha + IL-1beta
CD8 lymphocyte act	35.1	Astrocytes rest	2.9
Secondary CD8	38.7	Astrocytes TNF alpha + IL-	1.1
lymphocyte rest		1beta
Secondary CD8	24.5	KU-812 (Basophil) rest	6.5
lymphocyte act
CD4 lymphocyte none	31.4	KU-812 (Basophil)	6.1
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	54.0	CCD1106 (Keratinocytes)	1.7
CD95 CH11		none
LAK cells rest	16.3	CCD1106 (Keratinocytes)	3.2
		TNF alpha + IL-1beta
LAK cells IL-2	32.5	Liver cirrhosis	5.3
LAK cells IL-2 + IL-12	21.3	NCI-H292 none	5.2
LAK cells IL-2 + IFN	40.1	NCI-H292 IL-4	6.7
gamma
LAK cells IL-2 + IL-18	47.6	NCI-H292 IL-9	8.1
LAK cells PMA/ionomycin	8.4	NCI-H292 IL-13	5.5
NK Cells IL-2 rest	59.5	NCI-H292 IFN gamma	6.2
Two Way MLR 3 day	36.3	HPAEC none	9.9
Two Way MLR 5 day	29.1	HPAEC TNF alpha + IL-1	12.5
		beta
Two Way MLR 7 day	40.3	Lung fibroblast none	2.9
PBMC rest	21.9	Lung fibroblast TNF	3.0
		alpha + IL-1beta
PBMC PWM	14.5	Lung fibroblast IL-4	2.6
PBMC PHA-L	26.4	Lung fibroblast IL-9	2.4
Ramos (B cell) none	29.3	Lung fibroblast IL-13	3.3
Ramos (B cell) ionomycin	26.8	Lung fibroblast IFN	3.7
		gamma
B lymphocytes PWM	25.3	Dermal fibroblast	7.6
		CCD1070 rest
B lymphocytes CD40L and	33.2	Dermal fibroblast	50.7
IL-4		CCD1070 TNF alpha
EOL-1 dbcAMP	19.6	Dermal fibroblast	3.2
		CCD1070 IL-1beta
EOL-1 dbcAMP	8.9	Dermal fibroblast IFN	5.2
PMA/ionomycin		gamma
Dendritic cells none	9.0	Dermal fibroblast IL-4	4.3
Dendritic cells LPS	4.7	Dermal Fibroblasts rest	5.5
Dendritic cells anti-CD40	5.4	Neutrophils TNFa + LPS	2.0
Monocytes rest	7.9	Neutrophils rest	6.5
Monocytes LPS	2.5	Colon	6.0
Macrophages rest	5.2	Lung	6.8
Macrophages LPS	1.8	Thymus	100.0
HUVEC none	7.8	Kidney	21.2
HUVEC starved	8.4

[0673]

TABLE IE
Panel CNS_1.1
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4243,		Ag4243, Run
Tissue Name	Run 195308641	Tissue Name	195308641
Cing Gyr Depression2	62.9	BA17 PSP2	20.7
Cing Gyr Depression	24.5	BA17 PSP	82.4
Cing Gyr PSP2	17.0	BA17 Huntington's2	35.4
Cing Gyr PSP	57.4	BA17 Huntington's	40.9
Cing Gyr Huntington's2	19.3	BA17 Parkinson's2	45.4
Cing Gyr Huntington's	93.3	BA17 Parkinson's	90.1
Cing Gyr Parkinson's2	40.3	BA17 Alzheimer's2	60.3
Cing Gyr Parkinson's	46.0	BA17 Control2	19.3
Cing Gyr Alzheimer's2	29.1	BA17 Control	57.0
Cing Gyr Alzheimer's	21.2	BA9 Depression2	41.5
Cing Gyr Control2	11.7	BA9 Depression	15.2
Cing Gyr Control	24.3	BA9 PSP2	23.5
Temp Pole Depression2	13.0	BA9 PSP	30.8
Temp Pole PSP2	0.0	BA9 Huntington's2	24.0
Temp Pole PSP	20.9	BA9 Huntington's	48.6
Temp Pole Huntington's	42.0	BA9 Parkinson's2	62.9
Temp Pole Parkinson's2	31.6	BA9 Parkinson's	48.0
Temp Pole Parkinson's	57.0	BA9 Alzheimer's2	11.7
Temp Pole Alzheimer's2	29.5	BA9 Alzheimer's	0.0
Temp Pole Alzheimer's	18.6	BA9 Control2	66.0
Temp Pole Control2	38.2	BA9 Control	11.1
Temp Pole Control	14.9	BA7 Depression	10.0
Glob Palladus Depression	11.9	BA7 PSP2	19.8
Glob Palladus PSP2	0.0	BA7 PSP	78.5
Glob Palladus PSP	6.5	BA7 Huntington's2	67.8
Glob Palladus Parkinson's2	14.5	BA7 Huntington's	39.8
Glob Palladus Parkinson's	84.7	BA7 Parkinson's2	27.0
Glob Palladus	18.8	BA7 Parkinson's	100.0
Alzheimer's2
Glob Palladus Alzheimer's	30.4	BA7 Alzheimer's2	24.0
Glob Palladus Control2	15.5	BA7 Control2	20.4
Glob Palladus Control	6.1	BA7 Control	31.2
Sub Nigra Depression2	20.0	BA4 Depression2	27.2
Sub Nigra Depression	45.7	BA4 Depression	28.7
Sub Nigra PSP2	5.9	BA4 PSP2	26.2
Sub Nigra Huntington's2	80.7	BA4 PSP	11.4
Sub Nigra Huntington's	76.8	BA4 Huntington's2	24.1
Sub Nigra Parkinson's2	0.0	BA4 Huntington's	57.0
Sub Nigra Alzheimer's2	11.1	BA4 Parkinson's2	82.9
Sub Nigra Control2	33.9	BA4 Parkinson's	56.6
Sub Nigra Control	55.1	BA4 Alzheimer's2	27.2
BA17 Depression2	92.0	BA4 Control2	68.3
BA17 Depression	33.0	BA4 Control	18.7

[0674]

TABLE IF
general oncology screening panel_v_2.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4243, Run		Ag4243, Run
Tissue Name	268664318	Tissue Name	268664318
Colon cancer 1	5.3	Bladder cancer NAT 2	1.0
Colon cancer NAT 1	0.0	Bladder cancer NAT 3	0.0
Colon cancer 2	13.4	Bladder cancer NAT 4	6.2
Colon cancer NAT 2	0.0	Adenocarcinoma of the	0.0
		prostate 1
Colon cancer 3	31.0	Adenocarcinoma of the	0.0
		prostate 2
Colon cancer NAT 3	40.9	Adenocarcinoma of the	4.0
		prostate 3
Colon malignant cancer 4	4.2	Adenocarcinoma of the	3.0
		prostate 4
Colon normal adjacent	20.6	Prostate cancer NAT 5	3.8
tissue 4
Lung cancer 1	6.7	Adenocarcinoma of the	2.1
		prostate 6
Lung NAT 1	0.0	Adenocarcinoma of the	1.9
		prostate 7
Lung cancer 2	0.0	Adenocarcinoma of the	5.7
		prostate 8
Lung NAT 2	3.2	Adenocarcinoma of the	26.6
		prostate 9
Squamous cell carcinoma 3	31.0	Prostate cancer NAT 10	0.0
Lung NAT 3	3.0	Kidney cancer 1	42.6
metastatic melanoma 1	0.1	KidneyNAT 1	13.8
Melanoma 2	0.0	Kidney cancer 2	100.0
Melanoma 3	6.3	Kidney NAT 2	38.2
metastatic melanoma 4	33.7	Kidney cancer 3	9.7
metastatic melanoma 5	24.1	Kidney NAT 3	9.5
Bladder cancer 1	0.0	Kidney cancer 4	1.9
Bladder cancer NAT 1	0.0	Kidney NAT 4	4.6
Bladder cancer 2	6.2

[0675] CNS_neurodegeneration_v1.0 Summary: Ag4243 This panel confirms the presence of this gene in the brain. Please see Panel 1.4 for discussion of this gene in the central nervous system.

[0676] General_screening_panel_v1.4 Summary: Ag4243 Highest expression of this gene is seen in a brain cancer cell line (CT=25.9). In addition, this gene appears to be more highly expressed in fetal tissues and cancer cell lines, with moderate to high levels of expression in colon, lung, breast, prostate, and melanoma cancer cell lines. Thus, expression of this gene could be used to differentiate the brain cancer cell line from other samples on this panel and as a marker of brain cancer. This expression profile also suggests a role for this gene product in cell survival and proliferation. This gene is homologous to members of the septin family. Septins are a family of conserved GTPases that have been implicated in a variety of cellular functions involving specialized regions of the cell cortex and changes in cell shape (1). Recent work also suggests novel functions for septins in vesicle trafficking, oncogenesis and compartmentalization of the plasma membrane (2). For example, a human septin gene has recently been identified that is commonly deleted in sporadic epithelial ovarian tumors and is therefore a candidate ovarian tumor suppressor gene (3). Given the ability of the septins to bind GTP and phosphatidylinositol 4,5-bisphosphate in a mutually exclusive manner, these proteins might be crucial elements for the spatial and/or temporal control of diverse cellular functions (2). Therefore, modulation of this gene product may be useful in the treatment of cancer.

[0677] Among tissues with metabolic function, this gene is expressed at high levels in adrenal, moderate levels in pituitary, adipose, pancreas, fetal liver and skeletal muscle, adult and fetal liver, and low but significant levels in thyroid, liver, and skeletal muscle. Based on its potential effects on signalling and vesicle trafficking, targeting this septin-like gene might also provide a valuable treatment for metabolic diseases, including diabetes and obesity.

[0678] This gene is also expressed at moderate to low levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. A septin that is preferentially expressed in the nervous system has been described and is proposed to regulate vesicle dynamics through interactions with syntaxin (4). Furthermore, septins have been found in neurofibrillary tangles in Alzheimer's disease, suggesting that septins may play a role in neurological diseases (5). Similarly, comparative immunohistochemical analysis of several mouse septins suggests that mouse septin 6 is associated with synaptic vesicles in various brain regions, including glomeruli of the olfactory bulb (6). Based on the homology of this protein to septin and its expression in this panel, this gene product may play a role in the regulation of cytoskeletal function, the assembly of signalling complexes, vesicle trafficking, and compartmentalization of the plasma membrane. 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.

[0679] References:

[0680] 1. Field C. M., Kellogg D. (1999) Septins: cytoskeletal polymers or signalling GTPases? Trends Cell. Biol. 9: 387-394.

[0681] 2. Kartmann B., Roth D. (2001) Novel roles for mammalian septins: from vesicle trafficking to oncogenesis. J. Cell. Sci. 114: 839-844.

[0682] 3. Russell S. E., McIlhatton M. A., Burrows J. F., Donaghy P. G., Chanduloy S., Petty E. M., Kalikin L. M., Church S. W., Mcllroy S., Harkin D. P., Keilty G. W., Cranston A. N., Weissenbach J., Hickey I., Johnston P. G. (2000) Isolation and mapping of a human septin gene to a region on chromosome 17q, commonly deleted in sporadic epithelial ovarian tumors. Cancer Res. 60: 4729-4734.

[0683] 4. Kinoshita A., Noda M., Kinoshita M. (2000) Differential localization of septins in the mouse brain. J. Comp. Neurol. 428: 223-239.

[0684] 5. Kinoshita A., Kinoshita M., Akiyama H., Tomimoto H., Akiguchi I., Kumar S., Noda M., Kimura J. (1998) Identification of septins in neurofibrillary tangles in Alzheimer's disease. Am. J. Pathol. 153: 1551-1560.

[0685] 6. Beites C. L., Xie H., Bowser R., Trimble W. S. (1999) The septin CDCrel-1 binds syntaxin and inhibits exocytosis. Nat. Neurosci. 2: 434439.

[0686] Panel 4.1D Summary: Ag4243 Highest expression of this gene is in the thymus (CT=28.3). In addition, moderate levels of expression are seen in many hematopoietic cell types, including activated and resting Th1, Th2, and Tr1 cells, LAK cells and B cells. Therefore, the putative protein encoded by this gene could potentially be used diagnostically to identify B or T cells. In addition, the gene product could also potentially be used therapeutically in the treatment of asthma, emphysema, IBD, lupus or arthritis and in other diseases in which T cells and B cells are involved.

[0687] Panel CNS—1.1 Summary: Ag4243 This panel confirms the presence of this gene in the brain. See Panel 1.4 for discussion of this gene in the central nervous system.

[0688] General oncology screening panel_v—2.4 Summary: Ag4243 Highest expression of this gene is in the kidney cancer sample (CT=28.7). In addition, moderate to high expression of this gene is seen in number of cancer samples including melanoma, colon, lung, bladder, kidney and prostate cancers. Interestingly, expression of this gene is higher in some of the colon and lung cancers as compared to matching control samples. Therefore, expression of this gene may used as a diagnostic marker for detection of melanoma, lung, colon, prostate and kidney cancers. Furthermore, therapeutic modulation of this gene product may be useful in the treatment of these cancers.

J. CG102899-01: RIM2-4C

[0689] Expression of gene CG102899-01 was assessed using the primer-probe set Ag4247, described in Table JA. Results of the RTQ-PCR runs are shown in Tables JB, JC, JD, JE and JF.

TABLE JA
Probe Name Ag4247
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-attagatgatgagccacattgg-3′	22	2586	116
Probe	TET-5′-acgcatgatgtctcttcattgccact-3′-TAMRA	26	2620	117
Reverse	5′-tgtcttcgtggcatatatgga-3′	21	2658	118

[0690]

TABLE JB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4247, Run		Ag4247, Run
Tissue Name	224077628	Tissue Name	224077628
AD 1 Hippo	6.0	Control (Path) 3 Temporal	5.0
		Ctx
AD 2 Hippo	13.7	Control (Path) 4 Temporal	37.9
		Ctx
AD 3 Hippo	4.4	AD 1 Occipital Ctx	17.7
AD 4 Hippo	4.0	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 hippo	82.9	AD 3 Occipital Ctx	3.6
AD 6 Hippo	22.1	AD 4 Occipital Ctx	19.9
Control 2 Hippo	19.8	AD 5 Occipital Ctx	38.2
Control 4 Hippo	3.9	AD 6 Occipital Ctx	47.0
Control (Path) 3 Hippo	4.5	Control 1 Occipital Ctx	2.5
AD 1 Temporal Ctx	9.5	Control 2 Occipital Ctx	75.3
AD 2 Temporal Ctx	25.3	Control 3 Occipital Ctx	18.6
AD 3 Temporal Ctx	5.1	Control 4 Occipital Ctx	3.7
AD 4 Temporal Ctx	26.1	Control (Path) 1 Occipital	100.0
		Ctx
AD 5 Inf Temporal Ctx	88.9	Control (Path) 2 Occipital	13.3
		Ctx
AD 5 SupTemporal Ctx	10.6	Control (Path) 3 Occipital	1.4
		Ctx
AD 6 Inf Temporal Ctx	42.3	Control (Path) 4 Occipital	14.2
		Ctx
AD 6 Sup Temporal Ctx	44.4	Control 1 Parietal Ctx	7.4
Control 1 Temporal Ctx	6.3	Control 2 Parietal Ctx	32.8
Control 2 Temporal Ctx	47.0	Control 3 Parietal Ctx	20.3
Control 3 Temporal Ctx	18.7	Control (Path) 1 Parietal	97.9
		Ctx
Control 4 Temporal Ctx	10.6	Control (Path) 2 Parietal	28.1
		Ctx
Control (Path) 1 Temporal	67.4	Control (Path) 3 Parietal	3.9
Ctx		Ctx
Control (Path) 2 Temporal	50.3	Control (Path) 4 Parietal	49.3
Ctx		Ctx

[0691]

TABLE JC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4247, Run		Ag4247, Run
Tissue Name	222019642	Tissue Name	222019642
Adipose	0.1	Renal ca. TK-10	24.7
Melanoma* Hs688(A).T	0.6	Bladder	1.3
Melanoma* Hs688(B).T	0.7	Gastric ca. (liver met.)	0.4
		NCI-N87
Melanoma* M14	0.5	Gastric ca. KATO III	0.0
Melanoma* LOXIMVI	2.2	Colon ca. SW-948	0.0
Melanoma* SK-MEL-5	8.4	Colon ca. SW480	23.7
Squamous cell carcinoma	0.8	Colon ca.* (SW480 met)	0.7
SCC-4		SW620
Testis Pool	4.9	Colon ca. HT29	0.0
Prostate ca.* (bone met)	0.0	Colon ca. HCT-116	0.5
PC-3
Prostate Pool	4.9	Colon ca. CaCo-2	0.1
Placenta	0.0	Colon cancer tissue	0.0
Uterus Pool	0.4	Colon ca. SW1116	0.0
Ovarian ca. OVCAR-3	6.5	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	2.0	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	0.0	Colon Pool	1.1
Ovarian ca. OVCAR-5	0.4	Small Intestine Pool	0.2
Ovarian ca. IGROV-1	0.3	Stomach Pool	0.6
Ovarian ca. OVCAR-8	4.3	Bone Marrow Pool	0.1
Ovary	0.2	Fetal Heart	0.3
Breast ca. MCF-7	0.4	Heart Pool	1.1
Breast ca. MDA-MB-231	0.0	Lymph Node Pool	0.7
Breast ca. BT 549	6.0	Fetal Skeletal Muscle	0.0
Breast ca. T47D	0.4	Skeletal Muscle Pool	0.0
Breast ca. MDA-N	0.0	Spleen Pool	2.3
Breast Pool	1.4	Thymus Pool	0.8
Trachea	0.4	CNS cancer (glio/astro)	3.0
		U87-MG
Lung	1.2	CNS cancer (glio/astro) U-	0.1
		118-MG
Fetal Lung	0.7	CNS cancer (neuro; met)	4.5
		SK-N-AS
Lung ca. NCI-N417	8.4	CNS cancer (astro) SF-	2.4
		539
Lung ca. LX-1	4.5	CNS cancer (astro) SNB-	0.1
		75
Lung ca. NCI-H146	35.6	CNS cancer (glio) SNB-19	0.0
Lung ca. SHP-77	100.0	CNS cancer (glio) SF-295	0.4
Lung ca. A549	0.1	Brain (Amygdala) Pool	48.0
Lung ca. NCI-H526	18.8	Brain (cerebellum)	43.2
Lung ca. NCI-H23	85.9	Brain (fetal)	42.3
Lung ca. NCI-H460	0.2	Brain (Hippocampus) Pool	45.1
Lung ca. HOP-62	0.8	Cerebral Cortex Pool	82.4
Lung ca. NCI-H522	22.1	Brain (Substantia nigra)	47.6
		Pool
Liver	0.0	Brain (Thalamus) Pool	75.3
Fetal Liver	0.2	Brain (whole)	46.7
Liver ca. HepG2	0.0	Spinal Cord Pool	10.7
Kidney Pool	4.9	Adrenal Gland	7.2
Fetal Kidney	0.7	Pituitary gland Pool	21.8
Renal ca. 786-0	0.0	Salivary Gland	0.0
Renal ca. A498	0.0	Thyroid (female)	1.2
Renal ca. ACHN	12.5	Pancreatic ca. CAPAN2	0.1
Renal ca. UO-31	0.3	Pancreas Pool	1.4

[0692]

TABLE JD
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4247, Run		Ag4247, Run
Tissue Name	175165711	Tissue Name	175165711
Secondary Th1 act	1.0	HUVEC IL-1beta	3.3
Secondary Th2 act	17.2	HUVEC IFN gamma	27.0
Secondary Tr1 act	14.7	HUVEC TNF alpha + IFN	8.9
		gamma
Secondary Th1 rest	2.1	HUVEC TNF alpha + IL4	3.7
Secondary Th2 rest	4.6	HUVEC IL-11	11.4
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	1.6	Microvascular Dermal EC	0.0
		none
Primary Tr1 act	3.2	Microsvasular Dermal EC	0.0
		TNF alpha + IL-1beta
Primary Th1 rest	0.5	Bronchial epithelium	20.0
		TNF alpha + IL1beta
Primary Th2 rest	0.0	Small airway epithelium	2.2
		none
Primary Tr1 rest	0.5	Small airway epithelium	4.8
		TNF alpha + IL-1beta
CD45RA CD4 lymphocyte	1.2	Coronery artery SMC rest	0.0
act
CD45RO CD4 lymphocyte	0.4	Coronery artery SMC	1.6
act		TNF alpha + IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	5.0
Secondary CD8 lymphocyte	0.6	Astrocytes TNF alpha +	8.5
rest		IL-1beta
Secondary CD8 lymphocyte	0.6	KU-812 (Basophil) rest	0.9
act
CD4 lymphocyte none	0.5	KU-812 (Basophil)	0.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	0.8	CCD1106 (Keratinocytes)	55.9
CH11		none
LAK cells rest	0.0	CCD1106 (Keratinocytes)	95.9
		TNF alpha + IL-1beta
LAK cells IL-2	0.5	Liver cirrhosis	0.2
LAK cells IL-2 + IL-12	1.0	NCI-H292 none	21.2
LAK cells IL-2 + IFN gamma	0.7	NCI-H292 IL-4	25.3
LAK cells IL-2 + IL-18	0.5	NCI-H292 IL-9	28.7
LAK cells PMA/ionomycin	0.5	NCI-H292 IL-13	27.7
NK Cells IL-2 rest	0.0	NCI-H292 IFN gamma	28.7
Two Way MLR 3 day	0.0	HPAEC none	6.0
Two Way MLR 5 day	1.7	HPAEC TNF alpha +	14.9
		IL-1beta
Two Way MLR 7 day	2.0	Lung fibroblast none	1.5
PBMC rest	0.0	Lung fibroblast	0.6
		TNF alpha + IL-1beta
PBMC PWM	0.0	Lung fibroblast IL-4	0.6
PBMC PHA-L	1.5	Lung fibroblast IL-9	2.1
Ramos (B cell) none	3.8	Lung fibroblast IL-13	0.0
Ramos (B cell) ionomycin	1.8	Lung fibroblast IFN	3.4
		gamma
B lymphocytes PWM	0.0	Dermal fibroblast	5.8
		CCD1070 rest
B lymphocytes CD40L and	0.5	Dermal fibroblast	2.7
IL-4		CCD1070 TNF alpha
EOL-1 dbcAMP	0.0	Dermal fibroblast	0.6
		CCD1070 IL-1beta
EOL-1 dbcAMP	0.0	Dermal fibroblast IFN	6.8
PMA/ionomycin		gamma
Dendritic cells none	0.5	Dermal fibroblast IL-4	4.8
Dendritic cells LPS	2.5	Dermal Fibroblasts rest	3.6
Dendritic cells anti-CD40	0.6	Neutrophils TNFa + LPS	2.3
Monocytes rest	0.0	Neutrophils rest	0.2
Monocytes LPS	0.0	Colon	4.4
Macrophages rest	0.5	Lung	0.7
Macrophages LPS	0.0	Thymus	18.2
HUVEC none	0.0	Kidney	100.0
HUVEC starved	0.0

[0693]

TABLE JE
Panel CNS_1
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4247, Run		Ag4247,
Tissue Name	181012676	Tissue Name	Run 181012676
BA4 Control	34.2	BA17 PSP	29.3
BA4 Control2	60.7	BA17 PSP2	15.8
BA4 Alzheimer's2	5.6	Sub Nigra Control	20.4
BA4 Parkinson's	65.5	Sub Nigra Control2	16.2
BA4 Parkinson's2	97.3	Sub Nigra Alzheimer's2	4.3
BA4 Huntington's	48.0	Sub Nigra Parkinson's2	34.6
BA4 Huntington's2	13.5	Sub Nigra Huntington's	28.9
BA4 PSP	9.5	Sub Nigra Huntington's2	24.5
BA4 PSP2	24.1	Sub Nigra PSP2	3.3
BA4 Depression	14.4	Sub Nigra Depression	2.1
BA4 Depression2	9.9	Sub Nigra Depression2	1.5
BA7 Control	53.2	Glob Palladus Control	9.7
BA7 Control2	55.1	Glob Palladus Control2	10.3
BA7 Alzheimer's2	9.1	Glob Palladus Alzheimer's	4.3
BA7 Parkinson's	30.8	Glob Palladus	3.5
		Alzheimer's2
BA7 Parkinson's2	58.6	Glob Palladus Parkinson's	97.9
BA7 Huntington's	68.8	Glob Palladus Parkinson's2	19.1
BA7 Huntington's2	75.3	Glob Palladus PSP	5.1
BA7 PSP	48.0	Glob Palladus PSP2	3.5
BA7 PSP2	35.6	Glob Palladus Depression	2.4
BA7 Depression	12.3	Temp Pole Control	21.5
BA9 Control	28.1	Temp Pole Control2	80.1
BA9 Control2	100.0	Temp Pole Alzheimer's	6.0
BA9 Alzheimer's	4.1	Temp Pole Alzheimer's2	3.6
BA9 Alzheimer's2	15.1	Temp Pole Parkinson's	45.7
BA9 Parkinson's	51.1	Temp Pole Parkinson's2	37.4
BA9 Parkinson's2	67.4	Temp Pole Huntington's	42.6
BA9 Huntington's	59.5	Temp Pole PSP	5.1
BA9 Huntington's2	27.0	Temp Pole PSP2	2.5
BA9 PSP	13.3	Temp Pole Depression2	5.2
BA9 PSP2	4.1	Cing Gyr Control	58.2
BA9 Depression	8.4	Cing Gyr Control2	31.9
BA9 Depression2	14.0	Cing Gyr Alzheimer's	15.9
BA17 Control	71.2	Cing Gyr Alzheimer's2	9.9
BA17 Control2	61.1	Cing Gyr Parkinson's	33.2
BA17 Alzheimer's2	5.1	Cing Gyr Parkinson's2	35.6
BA17 Parkinson's	45.4	Cing Gyr Huntington's	63.7
BA17 Parkinson's2	59.5	Cing Gyr Huntington's2	21.3
BA17 Huntington's	49.7	Cing Gyr PSP	10.4
BA17 Huntington's2	20.9	Cing Gyr PSP2	4.5
BA17 Depression	7.6	Cing Gyr Depression	7.6
BA17 Depression2	20.0	Cing Gyr Depression2	11.0

[0694]

TABLE JF
general oncology screening panel_v_2.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4247, Run		Ag4247, Run
Tissue Name	268664321	Tissue Name	268664321
Colon cancer 1	2.4	Bladder cancer NAT 2	0.0
Colon NAT 1	0.0	Bladder cancer NAT 3	15.9
Colon cancer 2	0.0	Bladder cancer NAT 4	1.3
Colon cancer NAT 2	2.9	Adenocarcinoma of the	30.8
		prostate 1
Colon cancer 3	0.0	Adenocarcinoma of the	21.3
		prostate 2
Colon cancer NAT 3	4.1	Adenocarcinoma of the	100.0
		prostate 3
Colon malignant cancer 4	1.1	Adenocarcinoma of the	8.3
		prostate 4
Colon normal adjacent	2.4	Prostate cancer NAT 5	4.5
tissue 4
Lung cancer 1	2.5	Adenocarcinoma of the	21.3
		prostate 6
Lung NAT 1	0.0	Adenocarcinoma of the	35.1
		prostate 7
Lung cancer 2	70.7	Adenocarcinoma of the	6.8
		prostate 8
Lung NAT 2	0.0	Adenocarcinoma of the	54.0
		prostate 9
Squamous cell carcinoma 3	56.3	Prostate cancer NAT 10	9.8
Lung NAT 3	0.0	Kidney cancer 1	0.0
metastatic melanoma 1	57.8	KidneyNAT 1	7.0
Melanoma 2	1.5	Kidney cancer 2	1.1
Melanoma 3	0.5	Kidney NAT 2	10.0
metastatic melanoma 4	32.8	Kidney cancer 3	0.0
metastatic melanoma 5	15.5	Kidney NAT 3	4.6
Bladder cancer 1	0.0	Kidney cancer 4	63.7
Bladder cancer NAT 1	0.0	Kidney NAT 4	4.5
Bladder cancer 2	45.1

[0695] CNS_neurodegeneration_v1.0 Summary: Ag4247 This panel confirms the presence of this gene in the brain. Please see Panel 1.4 for discussion of this gene in the central nervous system.

[0696] General_screening_panel_v1.4 Summary: Ag4247 Highest expression of this gene is seen in a lung cancer cell line (CT=26.1). In addition, significant levels of expression are seen in a cluster of lung 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 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.

[0697] In addition, this gene is expressed at high levels in all regions of the CNS examined. This gene is homologous to a RIM protein, a putative regulator of vesicle exocytosis during short-term plasticity. Thus, modulation of this gene product may be useful in the treatment of neurological disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.

[0698] Among tissues with metabolic function, this gene is expressed at moderate to low levels in pituitary, adrenal gland, pancreas, thyroid, and adult and fetal heart. This expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0699] Panel 4.1D Summary: Ag4247 Highest expression of this gene is seen in the kidney (CT=30.6). Moderate levels of expression are seen in both treated and untreated keratinocytes, with low but significant levels of expression in thymus, dermal fibroblasts, HPAECs, HUVECs, astrocytes, activated bronchial and small airway epithelium, and the NCI-H292 cell line. Thus, modulation of the expression or activity of the protein encoded by this may be useful in the treatment of psoriasis, wound healing and other inflammatory conditions that involve these cells.

[0700] Panel CNS—1 Summary: Ag4247 This panel confirms the presence of this gene in the brain. See Panel 1.4 for discussion of this gene in the central nervous system.

[0701] General oncology screening panel_v—2.4 Summary: Ag4247 Highest expression of this gene is seen in prostate cancer (CT=31.8). In addition, expression is seen in lung, kidney and melanoma cancers. The expression of this gene appears to be overexpressed in lung and kidney cancers when compared to expression in normal adjacent tissue. This prominent expression in cancer is in agreement with expression seen in Panel 1.4. Thus, modulation of the expression or function of this gene may be useful in the treatment of these cancers.

K. CG105444-01: Meningioma-Expressed Antigen 6/11 (MEA6) (MEA11)

[0702] Expression of gene CG105444-01 was assessed using the primer-probe set Ag4287, described in Table KA. Results of the RTQ-PCR runs are shown in Tables KB, KC and KD.

TABLE KA
Probe Name Ag4287
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-attcatctctccctgctgaaa-3′	21	2123	119
Probe	TET-5′-ctggccttattcctccacctcttgct-3′-TAMRA	26	2159	120
Reverse	5′-tgtatccactggaaacaatgg-3′	21	2197	121

[0703]

TABLE KB
CNS_neurodegeneration_v1.0
		Rel.	Rel.
		Exp. (%)	Exp. (%)
		Ag4287,	Ag4287,
		Run	Run
	Tissue Name	224075697	268773955
	AD 1 Hippo	7.6	1.0
	AD 2 Hippo	17.0	9.9
	AD 3 Hippo	4.7	3.6
	AD 4 Hippo	13.7	22.7
	AD 5 hippo	100.0	65.1
	AD 6 Hippo	43.2	77.9
	Control 2 Hippo	33.7	4.0
	Control 4 Hippo	23.0	39.0
	Control (Path) 3	15.1	31.4
	Hippo
	AD 1 Temporal	7.6	3.3
	Ctx
	AD 2 Temporal	9.7	6.5
	Ctx
	AD 3 Temporal	2.5	14.4
	Ctx
	AD 4 Temporal	11.0	7.4
	Ctx
	AD 5 Inf	39.8	37.4
	Temporal Ctx
	AD 5	11.3	18.2
	SupTemporal Ctx
	AD 6 Inf	30.6	47.0
	Temporal Ctx
	AD 6 Sup	55.5	71.7
	Temporal Ctx
	Control 1	3.5	1.8
	Temporal Ctx
	Control 2	13.5	0.0
	Temporal Ctx
	Control 3	15.5	31.9
	Temporal Ctx
	Control 4	9.0	27.7
	Temporal Ctx
	Control (Path) 1	31.2	35.8
	Temporal Ctx
	Control (Path) 2	36.6	37.4
	Temporal Ctx
	Control (Path) 3	16.8	27.5
	Temporal Ctx
	Control (Path) 4	42.3	45.1
	Temporal Ctx
	AD 1 Occipital	44.4	28.7
	Ctx
	AD 2 Occipital	0.0	0.0
	Ctx (Missing)
	AD 3 Occipital	5.1	14.2
	Ctx
	AD 4 Occipital	10.7	11.6
	Ctx
	AD 5 Occipital	42.0	7.0
	Ctx
	AD 6 Occipital	23.5	7.7
	Ctx
	Control 1	6.6	22.4
	Occipital Ctx
	Control 2	24.3	2.7
	Occipital Ctx
	Control 3	25.3	100.0
	Occipital Ctx
	Control 4	10.3	9.2
	Occipital Ctx
	Control (Path) 1	66.9	22.4
	Occipital Ctx
	Control (Path) 2	10.3	3.7
	Occipital Ctx
	Control (Path) 3	4.0	13.6
	Occipital Ctx
	Control (Path) 4	32.5	54.3
	Occipital Ctx
	Control 1	13.0	9.9
	Parietal Ctx
	Control 2	27.4	37.6
	Parietal Ctx
	Control 3	22.1	17.3
	Parietal Ctx
	Control (Path) 1	33.2	37.1
	Parietal Ctx
	Control (Path) 2	17.4	23.7
	Parietal Ctx
	Control (Path) 3	3.8	26.6
	Parietal Ctx
	Control (Path) 4	46.7	55.1
	Parietal Ctx

[0704]

TABLE KC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4287, Run		Ag4287, Run
Tissue Name	222182747	Tissue Name	222182747
Adipose	9.8	Renal ca. TK-10	65.5
Melanoma* Hs688(A).T	9.1	Bladder	28.7
Melanoma* Hs688(B).T	9.5	Gastric ca. (liver met.) NCI-	12.4
		N87
Melanoma* M14	5.0	Gastric ca. KATO III	46.7
Melanoma* LOXIMVI	0.2	Colon ca. SW-948	5.3
Melanoma* SK-MEL-5	0.2	Colon ca. SW480	100.0
Squamous cell carcinoma	11.7	Colon ca.* (SW480 met)	57.0
SCC-4		SW620
Testis Pool	18.7	Colon ca. HT29	25.0
Prostate ca.* (bone met)	20.0	Colon ca. HCT-116	19.2
PC-3
Prostate Pool	8.3	Colon ca. CaCo-2	8.5
Placenta	8.3	Colon cancer tissue	16.3
Uterus Pool	1.3	Colon ca. SW1116	10.1
Ovarian ca. OVCAR-3	21.2	Colon ca. Colo-205	5.9
Ovarian ca. SK-OV-3	13.4	Colon ca. SW-48	4.2
Ovarian ca. OVCAR-4	34.6	Colon Pool	22.8
Ovarian ca. OVCAR-5	47.6	Small Intestine Pool	10.6
Ovarian ca. IGROV-1	3.7	Stomach Pool	11.7
Ovarian ca. OVCAR-8	11.1	Bone Marrow Pool	7.3
Ovary	2.8	Fetal Heart	1.5
Breast ca. MCF-7	10.2	Heart Pool	2.5
Breast ca. MDA-MB-231	21.8	Lymph Node Pool	12.5
Breast ca. BT 549	0.2	Fetal Skeletal Muscle	3.1
Breast ca. T47D	57.4	Skeletal Muscle Pool	0.3
Breast ca. MDA-N	4.8	Spleen Pool	4.2
Breast Pool	9.8	Thymus Pool	13.8
Trachea	8.5	CNS cancer (glio/astro) U87-	0.2
		MG
Lung	2.8	CNS cancer (glio/astro) U-	1.2
		118-MG
Fetal Lung	55.9	CNS cancer (neuro; met) SK-	0.2
		N-AS
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-539	0.1
Lung ca. LX-1	82.9	CNS cancer (astro) SNB-75	3.9
Lung ca. NCI-H146	0.3	CNS cancer (glio) SNB-19	3.0
Lung ca. SHP-77	0.3	CNS cancer (glio) SF-295	6.6
Lung ca. A549	0.5	Brain (Amygdala) Pool	0.3
Lung ca. NCI-H526	1.3	Brain (cerebellum)	0.5
Lung ca. NCI-H23	4.4	Brain (fetal)	1.4
Lung ca. NCI-H460	2.6	Brain (Hippocampus) Pool	0.6
Lung ca. HOP-62	2.1	Cerebral Cortex Pool	0.6
Lung ca. NCI-H522	0.1	Brain (Substantia nigra) Pool	1.3
Liver	0.2	Brain (Thalamus) Pool	1.2
Fetal Liver	1.8	Brain (whole)	1.3
Liver ca. HepG2	6.0	Spinal Cord Pool	1.2
Kidney Pool	8.0	Adrenal Gland	3.6
Fetal Kidney	38.7	Pituitary gland Pool	3.3
Renal ca. 786-0	25.5	Salivary Gland	3.1
Renal ca. A498	43.5	Thyroid (female)	12.5
Renal ca. ACHN	4.5	Pancreatic ca. CAPAN2	30.1
Renal ca. UO-31	14.0	Pancreas Pool	24.8

[0705]

TABLE KD
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4287, Run		Ag4287, Run
Tissue Name	182392142	Tissue Name	182392142
Secondary Th1 act	5.1	HUVEC IL-1beta	0.8
Secondary Th2 act	14.8	HUVEC IFN gamma	20.6
Secondary Tr1 act	6.2	HUVEC TNF alpha + IFN	9.1
		gamma
Secondary Th1 rest	8.5	HUVEC TNF alpha + IL4	3.4
Secondary Th2 rest	17.8	HUVEC IL-11	0.9
Secondary Tr1 rest	16.2	Lung Microvascular EC none	2.9
Primary Th1 act	9.0	Lung Microvascular EC	0.8
		TNF alpha + IL-1beta
Primary Th2 act	14.3	Microvascular Dermal EC	0.1
		none
Primary Tr1 act	8.4	Microsvasular Dermal EC	0.0
		TNF alpha + IL-1beta
Primary Th1 rest	4.0	Bronchial epithelium	28.9
		TNF alpha + IL1beta
Primary Th2 rest	2.6	Small airway epithelium none	8.1
Primary Tr1 rest	9.3	Small airway epithelium	37.4
		TNF alpha + IL-1beta
CD45RA CD4 lymphocyte	8.7	Coronery artery SMC rest	5.4
act
CD45RO CD4 lymphocyte	20.0	Coronery artery SMC	5.8
act		TNF alpha + IL-1beta
CD8 lymphocyte act	4.9	Astrocytes rest	0.3
Secondary CD8 lymphocyte	10.4	Astrocytes TNF alpha + IL-	0.6
rest		1beta
Secondary CD8 lymphocyte	7.6	KU-812 (Basophil) rest	20.9
act
CD4 lymphocyte none	3.8	KU-812 (Basophil)	79.6
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	23.5	CCD1106 (Keratinocytes)	45.1
CD95 CH11		none
LAK cells rest	5.2	CCD1106 (Keratinocytes)	52.5
		TNF alpha + IL-1beta
LAK cells IL-2	2.0	Liver cirrhosis	14.8
LAK cells IL-2 + IL-12	4.4	NCI-H292 none	23.0
LAK cells IL-2 + IFN	8.0	NCI-H292 IL-4	25.0
gamma
LAK cells IL-2 + IL-18	5.2	NCI-H292 IL-9	31.6
LAK cells PMA/ionomycin	6.9	NCI-H292 IL-13	36.6
NK Cells IL-2 rest	6.0	NCI-H292 IFN gamma	34.4
Two Way MLR 3 day	12.7	HPAEC none	1.3
Two Way MLR 5 day	6.7	HPAEC TNF alpha +	1.6
		IL-1beta
Two Way MLR 7 day	11.5	Lung fibroblast none	10.7
PBMC rest	2.0	Lung fibroblast TNF alpha +	2.7
		IL-1beta
PBMC PWM	5.2	Lung fibroblast IL-4	3.5
PBMC PHA-L	15.1	Lung fibroblast IL-9	8.0
Ramos (B cell) none	0.0	Lung fibroblast IL-13	4.8
Ramos (B cell) ionomycin	0.1	Lung flbroblast IFN gamma	8.8
B lymphocytes PWM	5.3	Dermal fibroblast CCD1070	3.4
		rest
B lymphocytes CD40L and	10.4	Dermal fibroblast CCD1070	23.5
IL-4		TNF alpha
EOL-1 dbcAMP	0.1	Dermal fibroblast CCD1070	2.3
		IL-1beta
EOL-1 dbcAMP	0.0	Dermal fibroblast IFN gamma	7.1
PMA/ionomycin
Dendritic cells none	0.0	Dermal fibroblast IL-4	7.4
Dendritic cells LPS	0.1	Dermal Fibroblasts rest	5.1
Dendritic cells anti-CD40	0.0	Neutrophils TNFa + LPS	3.2
Monocytes rest	0.1	Neutrophils rest	0.1
Monocytes LPS	0.4	Colon	15.3
Macrophages rest	0.6	Lung	19.2
Macrophages LPS	1.0	Thymus	38.7
HUVEC none	0.2	Kidney	100.0
HUVEC starved	0.8

[0706] CNS_neurodegeneration_v1.0 Summary: Ag4287 Two experiments with same probe and primer sets are in good agreement. This panel confirms the expression of the CG105444-01 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. See Panel 1.4 for a discussion of this gene in treatment of central nervous system disorders.

[0707] General_screening_panel_v1.4 Summary: Ag4287 Highest expression of the CG105444-01 gene is detected in colon cancer SW480 cell line (CT=26.3). Significant expression is also seen in number of cancer cell lines derived from colon, renal, lung, liver, breast, ovarian, and brain cancers. Thus, expression of this gene may 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 colon, renal, lung, liver, breast, ovarian, and brain cancers.

[0708] The CG1105444-01 gene encodes a homolog of meningioma-expressed antigen 6/11 (MEA6). MGEA6 is overexpressed in meningioma and glioma tumor cells. Furthermore, the immune response to MGEA6/11 is frequent in both meningioma and glioma patients (Comtesse et al., 2002, Oncogene 21(2):239-47, PMID: 11803467). Thus, based on the homology, MEA6 like protein encoded by the CG105463-01 gene may play a role in pathology of meningioma and glioma and therapeutic modulation of this gene may be beneficial in the treatment of these tumors.

[0709] Among tissues with metabolic or endocrine function, this gene is expressed at moderate to low levels in pancreas, adipose, skeletal muscle, fetal 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.

[0710] Interestingly, this gene is expressed at much higher levels in fetal (CTs=27-32) when compared to adult liver, lung and skeletal muscle (CTs=3 1.5-35). This observation suggests that expression of this gene can be used to distinguish fetal liver, lung and skeletal muscle from corresponding adult tissues. In addition, the relative overexpression of this gene in fetal tissue suggests that the protein product may enhance growth or development of liver, lung and skeletal muscle in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of MEA6 like protein encoded by this gene could be useful in treatment of liver, lung and skeletal muscle related diseases.

[0711] In addition, this gene is expressed at moderate to 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.

[0712] Panel 4.1D Summary: Ag4287 Highest expression of the CG105444-01 gene is detected in kidney (CT=29). This gene is expressed at moderate to low 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.

L. CG105482-01: Meningioma-Expressed Antigen 6/11 (MEA6) (MEA11)

[0713] Expression of gene CG105482-01 was assessed using the primer-probe set Ag4319, described in Table LA. Results of the RTQ-PCR runs are shown in Tables LB, LC and LD.

TABLE LA
Probe Name Ag4319
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gggtcaatgccttcagaaat-3′	20	2047	122
Probe	TET-5′-agacatgatgccaaagatgatcctgg-3′-TAMRA	26	2077	123
Reverse	5′-cagcagggagagatgaatca-3′	20	2118	124

[0714]

TABLE LB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4319, Run		Ag4319, Run
Tissue Name	224074994	Tissue Name	224074994
AD 1 Hippo	7.6	Control (Path) 3 Temporal	38.2
		Ctx
AD 2 Hippo	20.9	Control (Path) 4 Temporal	36.9
		Ctx
AD 3 Hippo	11.3	AD 1 Occipital Ctx	61.6
AD 4 Hippo	6.7	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 hippo	41.8	AD 3 Occipital Ctx	18.2
AD 6 Hippo	12.9	AD 4 Occipital Ctx	5.2
Control 2 Hippo	7.9	AD 5 Occipital Ctx	0.0
Control 4 Hippo	11.6	AD 6 Occipital Ctx	0.0
Control (Path) 3 Hippo	10.4	Control 1 Occipital Ctx	4.6
AD 1 Temporal Ctx	26.8	Control 2 Occipital Ctx	13.0
AD 2 Temporal Ctx	5.3	Control 3 Occipital Ctx	100.0
AD 3 Temporal Ctx	14.4	Control 4 Occipital Ctx	12.9
AD 4 Temporal Ctx	35.1	Control (Path) 1 Occipital	22.5
		Ctx
AD 5 Inf Temporal Ctx	26.8	Control (Path) 2 Occipital	25.0
		Ctx
AD 5 Sup Temporal Ctx	26.1	Control (Path) 3 Occipital	0.0
		Ctx
AD 6 Inf Temporal Ctx	0.0	Control (Path) 4 Occipital	36.3
		Ctx
AD 6 Sup Temporal Ctx	8.5	Control 1 Parietal Ctx	18.7
Control 1 Temporal Ctx	15.9	Control 2 Parietal Ctx	80.7
Control 2 Temporal Ctx	0.0	Control 3 Parietal Ctx	13.3
Control 3 Temporal Ctx	13.5	Control (Path) 1 Parietal	25.3
		Ctx
Control 4 Temporal Ctx	0.0	Control (Path) 2 Parietal	15.6
		Ctx
Control (Path) 1 Temporal	44.4	Control (Path) 3 Parietal	25.0
Ctx		Ctx
Control (Path) 2 Temporal	56.3	Control (Path) 4 Parietal	14.7
Ctx		Ctx

[0715]

TABLE LC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4319, Run		Ag4319, Run
Tissue Name	222523501	Tissue Name	222523501
Adipose	1.4	Renal ca. TK-10	0.0
Melanoma* Hs688(A).T	0.0	Bladder	8.8
Melanoma* Hs688(B).T	0.0	Gastric ca. (liver met.)	0.0
		NCI-N87
Melanoma* M14	0.0	Gastric ca. KATO III	0.0
Melanoma* LOXIMVI	0.0	Colon ca. SW-948	0.0
Melanoma* SK-MEL-5	0.0	Colon ca. SW480	0.0
Squamous cell carcinoma	0.0	Colon ca.* (SW480 met)	0.0
SCC-4		SW620
Testis Pool	11.7	Colon ca. HT29	0.0
Prostate ca.* (bone met) PC-3	0.0	Colon ca. HCT-116	0.0
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. OVCAR-3	15.8	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	0.0	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	0.0	Colon Pool	0.0
Ovarian ca. OVCAR-5	0.0	Small Intestine Pool	0.0
Ovarian ca. IGROV-1	10.0	Stomach Pool	0.0
Ovarian ca. OVCAR-8	0.0	Bone Marrow Pool	0.0
Ovary	0.0	Fetal Heart	0.0
Breast ca. MCF-7	0.0	Heart Pool	0.0
Breast ca. MDA-MB-231	0.0	Lymph Node Pool	0.0
Breast ca. BT 549	1.4	Fetal Skeletal Muscle	0.0
Breast ca. T47D	0.0	Skeletal Muscle Pool	0.0
Breast ca. MDA-N	3.7	Spleen Pool	0.0
Breast Pool	0.0	Thymus Pool	0.0
Trachea	0.0	CNS cancer (glio/astro)	0.0
		U87-MG
Lung	0.0	CNS cancer (glio/astro) U-	0.0
		118-MG
Fetal Lung	0.0	CNS cancer (neuro; met)	22.7
		SK-N-AS
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-539	0.0
Lung ca. LX-1	0.0	CNS cancer (astro) SNB-	47.3
		75
Lung ca. NCI-H146	0.0	CNS cancer (glio) SNB-19	14.4
Lung ca. SHP-77	0.0	CNS cancer (glio) SF-295	0.0
Lung ca. A549	0.0	Brain (Amygdala) Pool	4.8
Lung ca. NCI-H526	0.0	Brain (cerebellum)	0.0
Lung ca. NCI-H23	0.0	Brain (fetal)	100.0
Lung ca. NCI-H460	0.0	Brain (Hippocampus) Pool	15.3
Lung ca. HOP-62	0.0	Cerebral Cortex Pool	51.1
Lung ca. NCI-H522	0.0	Brain (Substantia nigra)	13.9
		Pool
Liver	0.0	Brain (Thalamus) Pool	8.7
Fetal Liver	0.0	Brain (whole)	18.4
Liver ca. HepG2	0.0	Spinal Cord Pool	1.5
Kidney Pool	0.0	Adrenal Gland	0.0
Fetal Kidney	0.0	Pituitary gland Pool	0.0
Renal ca. 786-0	7.0	Salivary Gland	0.0
Renal ca. A498	10.4	Thyroid (female)	0.0
Renal ca. ACHN	0.0	Pancreatic ca. CAPAN2	0.0
Renal ca. UO-31	0.0	Pancreas Pool	0.0

[0716]

TABLE LD
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4319, Run		Ag4319, Run
Tissue Name	182392175	Tissue Name	182392175
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 + IFN	0.0
		gamma
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	0.0
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 EC	0.0
		none
Primary Tr1 act	0.0	Microsvasular Dermal EC	0.0
		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 lymphocyte	0.0	Coronery artery SMC rest	0.0
act
CD45RO CD4 lymphocyte	0.0	Coronery artery SMC	0.0
act		TNF alpha + IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	0.0
Secondary CD8 lymphocyte	0.0	Astrocytes TNF alpha + IL-	0.0
rest		1beta
Secondary CD8 lymphocyte	0.0	KU-812 (Basophil) rest	0.0
act
CD4 lymphocyte none	0.0	KU-812 (Basophil)	0.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	0.0	CCD1106 (Keratinocytes)	0.0
CH11		none
LAK cells rest	0.0	CCD1106 (Keratinocytes)	0.0
		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 gamma	0.0	NCI-H292 IL-4	0.0
LAK cells IL-2 + IL-18	0.0	NCI-H292 IL-9	0.0
LAK cells PMA/ionomycin	0.0	NCI-H292 IL-13	0.0
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 +	0.0
		IL-1beta
Two Way MLR 7 day	0.0	Lung fibroblast none	0.0
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) ionomycin	0.0	Lung fibroblast IFN	0.0
		gamma
B lymphocytes PWM	0.0	Dermal fibroblast	0.0
		CCD1070 rest
B lymphocytes CD40L and	0.0	Dermal fibroblast	0.0
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-CD40	0.0	Neutrophils TNFa + LPS	0.0
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	100.0
HUVEC starved	0.0

[0717] CNS_neurodegeneration_v1.0 Summary: Ag4319 This panel confirms the expression of the CG105482-01 gene at low levels in the brains of an independent group of individuals. See Panel 1.4 for a discussion of this gene in treatment of central nervous system disorders.

[0718] General_screening_panel_v1.4 Summary: Ag4319 Highest expression of the CG105482-01 gene is detected in fetal brain (CT=32.9). This gene is also expressed at low levels in cerebral cortex and a CNS cancer SNB-75 cell line. Therefore, expression of this gene may be used to distinguish brain samples from other samples used in this panel. Also, therapeutic modulation of this gene may be beneficial in the treatment of brain related diseases including brain cancer, and neurological disorders such as seizure and Huntington's disease.

[0719] The CG105482-01 gene encodes a homolog of meningioma-expressed antigen 6/11 (MEA6). MGEA6 is overexpressed in meningioma and glioma tumor cells. Furthermore, the immune response to MGEA6/11 is frequent in both meningioma and glioma patients (Comtesse et al., 2002, Oncogene 21(2):239-47, PMID: 11803467). Thus, based on the homology, MEA6 like protein encoded by the CG105482-01 gene may play a role in pathology of meningioma and glioma and therapeutic modulation of this gene may be beneficial in the treatment of these tumors.

[0720] Panel 4.1D Summary: Ag4319 Low levels of expression of the CG105482-01 gene is detected in kidney (CT=34.9). Therefore, expression of this gene may be used to distinguish kidney from other samples used in this panel. Furthermore, therapeutic modulation of this gene product may be useful in the treatment of autoimmune and inflammatory disease that affect kidney, including lupus and glomerulonephritis.

M. CG105617-01: Liprin alpha4

[0721] Expression of gene CG105617-01 was assessed using the primer-probe set Ag4294, described in Table MA.

TABLE MA
Probe Name Ag4294
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-tgccctactctgtttcttgtca-3′	22	691	125
Probe	TET-5′-atttctccctgccatggctggaag-3′-TAMRA	24	714	126
Reverse	5′-gggatagggacagtagctctgt-3′	22	748	127

N. CG105638-01: Ankyrin-like Q9GKW8 Homolog

[0722] Expression of gene CG105638-01 was assessed using the primer-probe set Ag3745, described in Table NA. Results of the RTQ-PCR runs are shown in Tables NB, NC, ND and NE.

TABLE NA
Probe Name Ag3745
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-cctggtggacatgatcataaaa-3′	22	717	128
Probe	TET-5′-ctacagatgggagaagaccaccccag-3′-TAMRA	26	750	129
Reverse	5′-cctgcttaaaggacaagctctt-3′	22	789	130

[0723]

TABLE NB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag3745, Run		Ag3745, Run
Tissue Name	212143924	Tissue Name	212143924
AD 1 Hippo	33.7	Control (Path) 3 Temporal	9.7
		Ctx
AD 2 Hippo	45.7	Control (Path) 4 Temporal	59.0
		Ctx
AD 3 Hippo	4.8	AD 1 Occipital Ctx	15.6
AD 4 Hippo	21.8	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 hippo	48.0	AD 3 Occipital Ctx	4.0
AD 6 Hippo	77.9	AD 4 Occipital Ctx	35.4
Control 2 Hippo	35.6	AD 5 Occipital Ctx	19.6
Control 4 Hippo	26.2	AD 6 Occipital Ctx	48.3
Control (Path) 3 Hippo	7.2	Control 1 Occipital Ctx	3.3
AD 1 Temporal Ctx	18.9	Control 2 Occipital Ctx	43.5
AD 2 Temporal Ctx	40.6	Control 3 Occipital Ctx	16.4
AD 3 Temporal Ctx	6.5	Control 4 Occipital Ctx	14.5
AD 4 Temporal Ctx	40.1	Control (Path) 1 Occipital	64.6
		Ctx
AD 5 Inf Temporal Ctx	81.8	Control (Path) 2 Occipital	7.6
		Ctx
AD 5 SupTemporal Ctx	69.7	Control (Path) 3 Occipital	1.8
		Ctx
AD 6 Inf Temporal Ctx	75.8	Control (Path) 4 Occipital	17.1
		Ctx
AD 6 Sup Temporal Ctx	100.0	Control 1 Parietal Ctx	10.9
Control 1 Temporal Ctx	8.7	Control 2 Parietal Ctx	52.9
Control 2 Temporal Ctx	45.7	Control 3 Parietal Ctx	22.2
Control 3 Temporal Ctx	16.7	Control (Path) 1 Parietal	68.3
		Ctx
Control 4 Temporal Ctx	16.7	Control (Path) 2 Parietal	33.7
		Ctx
Control (Path) 1 Temporal	73.7	Control (Path) 3 Parietal	6.1
Ctx		Ctx
Control (Path) 2 Temporal	51.8	Control (Path) 4 Parietal	60.3
Ctx		Ctx

[0724]

TABLE NC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag3745, Run		Ag3745, Run
Tissue Name	218297930	Tissue Name	218297930
Adipose	11.3	Renal ca. TK-10	0.6
Melanoma* Hs688(A).T	16.3	Bladder	18.4
Melanoma* Hs688(B).T	8.4	Gastric ca. (liver met.)	32.5
		NCI-N87
Melanoma* M14	9.0	Gastric ca. KATO III	0.3
Melanoma* LOXIMVI	2.6	Colon ca. SW-948	0.3
Melanoma* SK-MEL-5	6.7	Colon ca. SW480	4.5
Squamous cell carcinoma	5.6	Colon ca.* (SW480 met)	5.4
SCC-4		SW620
Testis Pool	36.3	Colon ca. HT29	0.8
Prostate ca.* (bone met) PC-3	11.4	Colon ca. HCT-116	42.6
Prostate Pool	17.2	Colon ca. CaCo-2	0.5
Placenta	22.2	Colon cancer tissue	7.0
Uterus Pool	12.4	Colon ca. SW1116	0.6
Ovarian ca. OVCAR-3	4.5	Colon ca. Colo-205	0.4
Ovarian ca. SK-OV-3	9.3	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	7.1	Colon Pool	34.2
Ovarian ca. OVCAR-5	41.2	Small Intestine Pool	21.2
Ovarian ca. IGROV-1	1.5	Stomach Pool	15.9
Ovarian ca. OVCAR-8	9.9	Bone Marrow Pool	18.0
Ovary	32.3	Fetal Heart	3.6
Breast ca. MCF-7	0.6	Heart Pool	18.8
Breast ca. MDA-MB-231	4.3	Lymph Node Pool	31.6
Breast ca. BT 549	6.7	Fetal Skeletal Muscle	3.7
Breast ca. T47D	56.6	Skeletal Muscle Pool	1.5
Breast ca. MDA-N	0.5	Spleen Pool	100.0
Breast Pool	31.0	Thymus Pool	14.6
Trachea	18.9	CNS cancer (glio/astro)	20.0
		U87-MG
Lung	16.8	CNS cancer (glio/astro)	14.9
		U-118-MG
Fetal Lung	25.5	CNS cancer (neuro; met)	17.9
		SK-N-AS
Lung ca. NCI-N417	1.6	CNS cancer (astro) SF-	17.8
		539
Lung ca. LX-1	4.1	CNS cancer (astro) SNB-	67.8
		75
Lung ca. NCI-H146	0.9	CNS cancer (glio) SNB-	2.2
		19
Lung ca. SHP-77	0.9	CNS cancer (glio) SF-295	13.9
Lung ca. A549	10.9	Brain (Amygdala) Pool	26.4
Lung ca. NCI-H526	28.3	Brain (cerebellum)	55.5
Lung ca. NCI-H23	33.2	Brain (fetal)	49.3
Lung ca. NCI-H460	4.0	Brain (Hippocampus) Pool	42.9
Lung ca. HOP-62	11.8	Cerebral Cortex Pool	53.6
Lung ca. NCI-H522	28.5	Brain (Substantia nigra)	42.3
		Pool
Liver	0.6	Brain (Thalamus) Pool	58.2
Fetal Liver	1.7	Brain (whole)	26.4
Liver ca. HepG2	0.2	Spinal Cord Pool	51.8
Kidney Pool	78.5	Adrenal Gland	74.2
Fetal Kidney	7.5	Pituitary gland Pool	1.4
Renal ca. 786-0	1.0	Salivary Gland	3.3
Renal ca. A498	3.1	Thyroid (female)	7.5
Renal ca. ACHN	1.0	Pancreatic ca. CAPAN2	12.3
Renal ca. UO-31	3.4	Pancreas Pool	25.9

[0725]

TABLE ND
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag3745, Run		Ag3745, Run
Tissue Name	170068389	Tissue Name	170068389
Secondary Th1 act	12.2	HUVEC IL-1beta	0.0
Secondary Th2 act	36.6	HUVEC IFN gamma	12.9
Secondary Tr1 act	54.3	HUVEC TNF alpha + IFN	8.8
		gamma
Secondary Th1 rest	1.2	HUVEC TNF alpha + IL4	8.7
Secondary Th2 rest	11.8	HUVEC IL-11	7.7
Secondary Tr1 rest	8.1	Lung Microvascular EC	17.6
		none
Primary Th1 act	4.8	Lung Microvascular EC	28.1
		TNF alpha + IL-1beta
Primary Th2 act	1.8	Microvascular Dermal EC	13.0
		none
Primary Tr1 act	1.5	Microsvasular Dermal EC	22.1
		TNF alpha + IL-1beta
Primary Th1 rest	34.6	Bronchial epithelium	28.3
		TNF alpha + IL1beta
Primary Th2 rest	14.3	Small airway epithelium	6.9
		none
Primary Tr1 rest	47.6	Small airway epithelium	8.5
		TNF alpha + IL-1beta
CD45RA CD4 lymphocyte	17.3	Coronery artery SMC rest	9.5
act
CD45RO CD4 lymphocyte	45.1	Coronery artery SMC	11.7
act		TNF alpha + IL-1beta
CD8 lymphocyte act	8.9	Astrocytes rest	5.1
Secondary CD8 lymphocyte	46.7	Astrocytes TNF alpha +	1.8
rest		IL-1beta
Secondary CD8 lymphocyte	39.8	KU-812 (Basophil) rest	9.3
act
CD4 lymphocyte none	11.7	KU-812 (Basophil)	14.1
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	28.7	CCD1106 (Keratinocytes)	8.5
CH11		none
LAK cells rest	34.6	CCD1106 (Keratinocytes)	3.9
		TNF alpha + IL-1beta
LAK cells IL-2	36.6	Liver cirrhosis	6.0
LAK cells IL-2 + IL-12	20.4	NCI-H292 none	2.4
LAK cells IL-2 + IFN gamma	47.0	NCI-H292 IL-4	0.0
LAK cells IL-2 + IL-18	27.5	NCI-H292 IL-9	0.0
LAK cells PMA/ionomycin	11.0	NCI-H292 IL-13	2.0
NK Cells IL-2 rest	94.0	NCI-H292 IFN gamma	0.0
Two Way MLR 3 day	23.7	HPAEC none	6.6
Two Way MLR 5 day	11.1	HPAEC TNF alpha +	8.0
		IL-1beta
Two Way MLR 7 day	46.3	Lung fibroblast none	100.0
PBMC rest	12.6	Lung fibroblast	27.5
		TNF alpha + IL-1beta
PBMC PWM	12.9	Lung fibroblast IL-4	44.8
PBMC PHA-L	5.7	Lung fibroblast IL-9	38.7
Ramos (B cell) none	9.7	Lung fibroblast IL-13	35.8
Ramos (B cell) ionomycin	23.3	Lung fibroblast IFN	69.3
		gamma
B lymphocytes PWM	1.4	Dermal fibroblast	10.3
		CCD1070 rest
B lymphocytes CD40L and	7.9	Dermal fibroblast	68.8
IL-4		CCD1070 TNF alpha
EOL-1 dbcAMP	1.6	Dermal fibroblast	5.7
		CCD1070 IL-1beta
EOL-1 dbcAMP	20.7	Dermal fibroblast IFN	43.2
PMA/ionomycin		gamma
Dendritic cells none	28.1	Dermal fibroblast IL-4	80.7
Dendritic cells LPS	35.6	Dermal Fibroblasts rest	36.6
Dendritic cells anti-CD40	18.3	Neutrophils TNFa + LPS	11.0
Monocytes rest	22.7	Neutrophils rest	19.5
Monocytes LPS	27.5	Colon	6.1
Macrophages rest	42.0	Lung	13.9
Macrophages LPS	12.2	Thymus	50.7
HUVEC none	3.6	Kidney	10.5
HUVEC starved	6.8

[0726]

TABLE NE
general oncology screening panel_v_2.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag3745, Run		Ag3745, Run
Tissue Name	268389961	Tissue Name	268389961
Colon cancer 1	6.2	Bladder cancer NAT 2	0.8
Colon cancer NAT 1	5.2	Bladder cancer NAT 3	2.1
Colon cancer 2	3.6	Bladder cancer NAT 4	5.7
Colon cancer NAT 2	4.5	Adenocarcinoma of the	69.3
		prostate 1
Colon cancer 3	7.6	Adenocarcinoma of the	4.5
		prostate 2
Colon cancer NAT 3	14.0	Adenocarcinoma of the	14.6
		prostate 3
Colon malignant cancer 4	6.0	Adenocarcinoma of the	7.2
		prostate 4
Colon normal adjacent tissue 4	0.0	Prostate cancer NAT 5	3.5
Lung cancer 1	7.2	Adenocarcinoma of the	4.8
		prostate 6
Lung NAT 1	4.5	Adenocarcinoma of the	8.8
		prostate 7
Lung cancer 2	12.5	Adenocarcinoma of the	1.7
		prostate 8
Lung NAT 2	3.1	Adenocarcinoma of the	33.2
		prostate 9
Squamous cell carcinoma 3	6.1	Prostate cancer NAT 10	2.1
Lung NAT 3	0.4	Kidney cancer 1	7.2
metastatic melanoma 1	37.1	KidneyNAT 1	2.0
Melanoma 2	3.2	Kidney cancer 2	27.7
Melanoma 3	3.1	Kidney NAT 2	7.6
metastatic melanoma 4	62.9	Kidney cancer 3	3.7
metastatic melanoma 5	100.0	Kidney NAT 3	3.4
Bladder cancer 1	2.9	Kidney cancer 4	4.1
Bladder cancer NAT 1	0.0	Kidney NAT 4	4.0
Bladder cancer 2	10.7

[0727] CNS_neurodegeneration_v1.0 Summary: Ag3745 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. See Panel 1.4 for discussion of this gene in the central nervous system.

[0728] General_screening_panel_v1.4 Summary: Ag3745 Highest expression of this gene is seen in the spleen (CT=29.6). This gene is widely expressed in this panel, with moderate expression seen in brain, colon, gastric, lung, breast, and ovarian cancer cell lines. Modulation of this gene product may be useful in the treatment of cancer.

[0729] Among tissues with metabolic function, this gene is expressed at moderate to low levels in adipose, adrenal gland, pancreas, thyroid, fetal skeletal muscle and adult and fetal heart. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0730] This gene is also expressed at moderate levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum 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.

[0731] Panel 4.ID Summary: Ag3745 Highest expression of this gene is seen in IL-4 treated fibroblasts (CT=31.2). In addition, prominent levels of expression are seen in treated and untreated lung and dermal fibroblasts, LAK cells, CD8 lymphocytes, chronically activated T cells, and primary resting T cells. Thus, this gene product may be involved in inflammatory conditions of the lung and skin, and T cell mediated autoimmune or inflammatory diseases, including asthma, allergies, inflammatory bowel disease, lupus erythematosus, or rheumatoid arthritis.

[0732] General oncology screening panel_V—2.4 Summary: Ag3745 Highest expression of this gene is seen in melanoma (CT=30.3). In addition, significant expression is seen in prostate and kidney cancer. This gene is overexpressed in kidney cancer when compared to expression in normal adjacent tissue. Thus, modulation of the expression or function of this gene may be useful in the treatment of these cancers.

O. CG105671-01: Novel GTPase Acivator Protein

[0733] Expression of gene CG105671 -01 was assessed using the primer-probe set Ag4295, described in Table OA. Results of the RTQ-PCR runs are shown in Tables OB, OC and OD.

TABLE OA
Probe Name Ag4295
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-aacaaagaaagtggaggtggat-3′	22	1600	131
Probe	TET-5′-cccacttacaaatgtcttcacgatgca-3′-TAMRA	27	1629	132
Reverse	5′-catgtggcaaagagagtcaga-3′	21	1662	133

[0734]

TABLE OB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4295, Run		Ag4295, Run
Tissue Name	224073754	Tissue Name	224073754
AD 1 Hippo	4.5	Control (Path) 3 Temporal	2.0
		Ctx
AD 2 Hippo	12.2	Control (Path) 4 Temporal	15.5
		Ctx
AD 3 Hippo	2.1	AD 1 Occipital Ctx	8.5
AD 4 Hippo	3.1	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 Hippo	100.0	AD 3 Occipital Ctx	1.1
AD 6 Hippo	18.2	AD 4 Occipital Ctx	8.4
Control 2 Hippo	15.4	AD 5 Occipital Ctx	34.4
Control 4 Hippo	1.3	AD 6 Occipital Ctx	11.2
Control (Path) 3 Hippo	3.1	Control 1 Occipital Ctx	1.1
AD 1 Temporal Ctx	2.1	Control 2 Occipital Ctx	48.6
AD 2 Temporal Ctx	13.1	Control 3 Occipital Ctx	6.7
AD 3 Temporal Ctx	2.1	Control 4 Occipital Ctx	1.1
AD 4 Temporal Ctx	6.0	Control (Path) 1 Occipital	51.8
		Ctx
AD 5 Inf Temporal Ctx	45.7	Control (Path) 2 Occipital	6.3
		Ctx
AD 5 Sup Temporal Ctx	17.2	Control (Path) 3 Occipital	1.1
		Ctx
AD 6 Inf Temporal Ctx	19.1	Control (Path) 4 Occipital	7.6
		Ctx
AD 6 Sup Temporal Ctx	18.0	Control 1 Parietal Ctx	1.9
Control 1 Temporal Ctx	1.4	Control 2 Parietal Ctx	16.3
Control 2 Temporal Ctx	22.8	Control 3 Parietal Ctx	10.0
Control 3 Temporal Ctx	4.8	Control (Path) 1 Parietal	54.0
		Ctx
Control 3 Temporal Ctx	1.3	Control (Path) 2 Parietal	11.7
		Ctx
Control (Path) 1 Temporal	35.8	Control (Path) 3 Parietal	0.9
Ctx		Ctx
Control (Path) 2 Temporal	15.9	Control (Path) 4 Parietal	27.4
Ctx		Ctx

[0735]

TABLE OC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4295, Run		Ag4295, Run
Tissue Name	222184063	Tissue Name	222184063
Adipose	1.2	Renal ca. TK-10	5.7
Melanoma* Hs688(A).T	0.3	Bladder	30.6
Melanoma* Hs688(B).T	0.6	Gastric ca. (liver met.) NCI-	49.3
		N87
Melanoma* M14	1.6	Gastric ca. KATO III	92.7
Melanoma* LOXIMVI	0.4	Colon ca. SW-948	16.5
Melanoma* SK-MEL-5	0.7	Colon ca. SW480	8.5
Squamous cell carcinoma	3.2	Colon ca.* (SW480 met)	7.6
SCC-4		SW620
Testis Pool	3.8	Colon ca. HT29	27.5
Prostate ca.* (bone met)	3.5	Colon ca. HCT-116	95.9
PC-3
Prostate Pool	3.8	Colon ca. CaCo-2	40.6
Placenta	1.0	Colon cancer tissue	30.4
Uterus Pool	2.8	Colon ca. SW1116	9.5
Ovarian ca. OVCAR-3	3.8	Colon ca. Colo-205	8.0
Ovarian ca. SK-OV-3	7.0	Colon ca. SW-48	1.6
Ovarian ca. OVCAR-4	6.1	Colon Pool	4.1
Ovarian ca. OVCAR-5	21.9	Small Intestine Pool	3.8
Ovarian ca. IGROV-1	0.6	Stomach Pool	5.3
Ovarian ca. OVCAR-8	2.6	Bone Marrow Pool	1.7
Ovary	3.2	Fetal Heart	0.9
Breast ca. MCF-7	72.2	Heart Pool	1.9
Breast ca. MDA-MB-231	0.9	Lymph Node Pool	5.4
Breast ca. BT 549	1.7	Fetal Skeletal Muscle	0.8
Breast ca. T47D	56.6	Skeletal Muscle Pool	0.2
Breast ca. MDA-N	0.1	Spleen Pool	1.9
Breast Pool	5.6	Thymus Pool	4.0
Trachea	19.6	CNS cancer (glio/astro)	1.1
		U87-MG
Lung	1.0	CNS cancer (glio/astro) U-	0.1
		118-MG
Fetal Lung	11.0	CNS cancer (neuro; met)	21.8
		SK-N-AS
Lung ca. NCI-N417	15.7	CNS cancer (astro) SF-539	0.1
Lung ca. LX-1	8.0	CNS cancer (astro) SNB-75	1.1
Lung ca. NCI-H146	14.9	CNS cancer (glio) SNB-19	0.6
Lung ca. SHP-77	24.3	CNS cancer (glio) SF-295	1.6
Lung ca. A549	5.3	Brain (Amygdala) Pool	12.6
Lung ca. NCI-H526	23.7	Brain (cerebellum)	32.1
Lung ca. NCI-H23	1.9	Brain (fetal)	100.0
Lung ca. NCI-H460	4.2	Brain (Hippocampus) Pool	9.6
Lung ca. HOP-62	0.1	Cerebral Cortex Pool	23.0
Lung ca. NCI-H522	0.9	Brain (Substantia nigra)	15.8
		Pool
Liver	0.1	Brain (Thalamus) Pool	25.0
Fetal Liver	1.6	Brain (whole)	27.2
Liver ca. HepG2	4.1	Spinal Cord Pool	6.7
Kidney Pool	4.0	Adrenal Gland	1.9
Fetal Kidney	5.8	Pituitary gland Pool	9.7
Renal ca. 786-0	0.5	Salivary Gland	18.0
Renal ca. A498	1.3	Thyroid (female)	0.6
Renal ca. ACHN	0.0	Pancreatic ca. CAPAN2	4.5
Renal ca. UO-31	0.4	Pancreas Pool	13.2

[0736]

TABLE OD
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4295, Run		Ag4295, Run
Tissue Name	181981934	Tissue Name	181981934
Secondary Th1 act	0.2	HUVEC IL-1beta	15.3
Secondary Th2 act	1.1	HUVEC IFN gamma	24.1
Secondary Tr1 act	0.0	HUVEC TNF alpha + IFN	11.8
		gamma
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	15.7
Secondary Th2 rest	0.0	HUVEC IL-11	6.3
Secondary Tr1 rest	0.4	Lung Microvascular EC	23.2
		none
Primary Th1 act	2.8	Lung Microvascular EC	19.2
		TNF alpha + IL-1beta
Primary Th2 act	0.6	Microvascular Dermal EC	16.0
		none
Primary Tr1 act	3.1	Microsvasular Dermal EC	10.8
		TNF alpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium	1.1
		TNF alpha + IL1beta
Primary Th2 rest	0.0	Small airway epithelium	0.7
		none
Primary Tr1 rest	0.3	Small airway epithelium	0.5
		TNF alpha + IL-1beta
CD45RA CD4 lymphocyte	1.5	Coronery artery SMC rest	0.0
act
CD45RO CD4 lymphocyte	1.6	Coronery artery SMC	0.7
act		TNF alpha + IL-1beta
CD8 lymphocyte act	0.3	Astrocytes rest	0.5
Secondary CD8 lymphocyte	1.1	Astrocytes TNF alpha + IL-	0.0
rest		1beta
Secondary CD8 lymphocyte	1.5	KU-812 (Basophil) rest	0.3
act
CD4 lymphocyte none	0.3	KU-812 (Basophil)	1.8
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	0.8	CCD1106 (Keratinocytes)	12.3
CD95 CH11		none
LAK cells rest	4.8	CCD1106 (Keratinocytes)	14.6
		TNF alpha + IL-1beta
LAK cells IL-2	1.0	Liver cirrhosis	5.2
LAK cells IL-2 + IL-12	1.6	NCI-H292 none	8.5
LAK cells IL-2 + IFN	1.8	NCI-H292 IL-4	10.5
gamma
LAK cells IL-2 + IL-18	4.7	NCI-H292 IL-9	15.8
LAK cells PMA/ionomycin	5.9	NCI-H292 IL-13	12.6
NK Cells IL-2 rest	1.4	NCI-H292 IFN gamma	26.6
Two Way MLR 3 day	2.6	HPAEC none	12.2
Two Way MLR 5 day	1.9	HPAEC TNF alpha +	22.4
		IL-1beta
Two Way MLR 7 day	4.2	Lung fibroblast none	0.0
PBMC rest	3.0	Lung fibroblast	0.6
		TNF alpha + IL-1beta
PBMC PWM	0.9	Lung fibroblast IL-4	0.0
PBMC PHA-L	2.0	Lung fibroblast IL-9	1.5
Ramos (B cell) none	0.0	Lung fibroblast IL-13	1.0
Ramos (B cell) ionomycin	0.3	Lung fibroblast IFN gamma	1.0
B lymphocytes PWM	2.8	Dermal fibroblast CCD1070	0.0
		rest
B lymphocytes CD40L and	1.1	Dermal fibroblast CCD1070	0.5
IL-4		TNF alpha
EOL-1 dbcAMP	1.5	Dermal fibroblast CCD1070	0.4
		IL-1beta
EOL-1 dbcAMP	1.3	Dermal fibroblast IFN	0.4
PMA/ionomycin		gamma
Dendritic cells none	2.4	Dermal fibroblast IL-4	2.4
Dendritic cells LPS	2.2	Dermal Fibroblasts rest	1.1
Dendritic cells anti-CD40	1.6	Neutrophils TNFa + LPS	13.2
Monocytes rest	5.2	Neutrophils rest	9.7
Monocytes LPS	100.0	Colon	1.5
Macrophages rest	17.8	Lung	13.6
Macrophages LPS	10.9	Thymus	4.4
HUVEC none	9.2	Kidney	6.2
HUVEC starved	5.1

[0737] CNS_neurodegeneration_v1.0 Summary: Ag4295 This panel confirms the presence of this gene in the brain. Please see Panel 1.4 for discussion of this gene in the central nervous system.

[0738] General_screening_panel_v1.4 Summary: Ag4295 Highest expression of this gene is seen in the fetal brain (CT=27.4). Thus, expression of this gene could be used to differentiate between fetal and adult brain tissue. In addition, this gene is expressed at moderate levels in all CNS regions examined. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurological disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.

[0739] This gene is highly expressed in clusters of cell lines derived from colon, gastric, and breast cancers. Thus, expression of this gene could be used as a marker of these cancers. Therapeutic modulation of this gene or gene product may be effective in the treatment of these cancers.

[0740] Among tissues with metabolic function, this gene is expressed at moderate to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, fetal skeletal muscle and liver, and adult and fetal heart. This expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0741] Panel 4.1D Summary: Ag4295 Highest expression of this gene is seen in LPS treated monocytes (CT=30). Low levels of expression are also seen in many samples on this panel, including LPS treated macrophages, treated and untreated HUVECs, NCI-H292 cells, HPAECs, activated neutrophils, and normal lung. The expression of this transcript in LPS treated monocytes, cells that play a crucial role in linking innate immunity to adaptive immunity, suggests a role for this gene product in initiating inflammatory reactions. Therefore, modulation of the expression or activity of this gene through the application of monoclonal antibodies may reduce or prevent early stages of inflammation and reduce the severity of inflammatory diseases such as psoriasis, asthma, inflammatory bowel disease, rheumatoid arthritis, osteoarthritis and other lung inflammatory diseases.

P. CG105778-01: PEFLIN Like Protein

[0742] Expression of gene CG105778-01 was assessed using the primer-probe set Ag4320, described in Table PA. Results of the RTQ-PCR runs are shown in Tables PB, PC and PD.

TABLE PA
Probe Name Ag4320
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-cacctccaaattcctacggt-3′	20	285	134
Probe	TET-5′-ctcatggacagggtggctcccct-3′-TAMRA	23	321	135
Reverse	5′-caggagtaggcctcatccat-3′	20	350	136

[0743]

TABLE PB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4320, Run		Ag4320, Run
Tissue Name	224075257	Tissue Name	224075257
AD 1 Hippo	13.6	Control (Path) 3 Temporal	3.0
		Ctx
AD 2 Hippo	13.3	Control (Path) 4 Temporal	76.8
		Ctx
AD 3 Hippo	8.0	AD 1 Occipital Ctx	13.2
AD 4 Hippo	9.5	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 Hippo	80.7	AD 3 Occipital Ctx	0.0
AD 6 Hippo	81.8	AD 4 Occipital Ctx	12.8
Control 2 Hippo	7.5	AD 5 Occipital Ctx	22.7
Control 4 Hippo	14.2	AD 6 Occipital Ctx	47.6
Control (Path) 3 Hippo	7.0	Control 1 Occipital Ctx	6.0
AD 1 Temporal Ctx	25.2	Control 2 Occipital Ctx	58.6
AD 2 Temporal Ctx	33.2	Control 3 Occipital Ctx	0.0
AD 3 Temporal Ctx	17.3	Control 4 Occipital Ctx	12.9
AD 4 Temporal Ctx	40.1	Control (Path) 1 Occipital	60.3
		Ctx
AD 5 Inf Temporal Ctx	82.4	Control (Path) 2 Occipital	12.9
		Ctx
AD 5 Sup Temporal Ctx	81.8	Control (Path) 3 Occipital	5.7
		Ctx
AD 6 Inf Temporal Ctx	53.6	Control (Path) 4 Occipital	0.0
		Ctx
AD 6 Sup Temporal Ctx	100.0	Control 1 Parietal Ctx	0.0
Control 1 Temporal Ctx	4.9	Control 2 Parietal Ctx	69.7
Control 2 Temporal Ctx	14.7	Control 3 Parietal Ctx	26.6
Control 3 Temporal Ctx	0.7	Control (Path) 1 Parietal	57.0
		Ctx
Control 3 Temporal Ctx	10.3	Control (Path) 2 Parietal	48.3
		Ctx
Control (Path) 1 Temporal	42.9	Control (Path) 3 Parietal	10.3
Ctx		Ctx
Control (Path) 2 Temporal	21.5	Control (Path) 4 Parietal	34.2
Ctx		Ctx

[0744]

TABLE PC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4320, Run		Ag4320, Run
Tissue Name	222523502	Tissue Name	222523502
Adipose	4.1	Renal ca. TK-10	27.4
Melanoma* Hs688(A).T	11.8	Bladder	30.6
Melanoma* Hs688(B).T	11.6	Gastric ca. (liver met.) NCI-	43.8
		N87
Melanoma* M14	11.2	Gastric ca. KATO III	30.6
Melanoma* LOXIMVI	6.6	Colon ca. SW-948	3.3
Melanoma* SK-MEL-5	27.0	Colon ca. SW480	13.4
Squamous cell carcinoma	2.3	Colon ca.* (SW480 met)	16.6
SCC-4		SW620
Testis Pool	3.3	Colon ca. HT29	6.7
Prostate ca.* (bone met)	27.0	Colon ca. HCT-116	35.4
PC-3
Prostate Pool	6.3	Colon ca. CaCo-2	16.8
Placenta	7.7	Colon cancer tissue	20.4
Uterus Pool	1.4	Colon ca. SW1116	4.7
Ovarian ca. OVCAR-3	42.0	Colon ca. Colo-205	8.0
Ovarian ca. SK-OV-3	50.3	Colon ca. SW-48	3.8
Ovarian ca. OVCAR-4	12.2	Colon Pool	5.0
Ovarian ca. OVCAR-5	41.8	Small Intestine Pool	25.5
Ovarian ca. IGROV-1	23.5	Stomach Pool	17.9
Ovarian ca. OVCAR-8	26.8	Bone Marrow Pool	9.5
Ovary	11.1	Fetal Heart	13.0
Breast ca. MCF-7	62.4	Heart Pool	6.2
Breast ca. MDA-MB-231	34.4	Lymph Node Pool	22.5
Breast ca. BT 549	52.1	Fetal Skeletal Muscle	2.7
Breast ca. T47D	100.0	Skeletal Muscle Pool	5.7
Breast ca. MDA-N	17.4	Spleen Pool	21.0
Breast Pool	10.9	Thymus Pool	54.0
Trachea	18.4	CNS cancer (glio/astro)	24.7
		U87-MG
Lung	11.0	CNS cancer (glio/astro) U-	30.4
		118-MG
Fetal Lung	55.5	CNS cancer (neuro; met)	94.6
		SK-N-AS
Lung ca. NCI-N417	7.2	CNS cancer (astro) SF-539	16.5
Lung ca. LX-1	14.1	CNS cancer (astro) SNB-75	46.3
Lung ca. NCI-H146	5.5	CNS cancer (glio) SNB-19	15.8
Lung ca. SHP-77	49.3	CNS cancer (glio) SF-295	25.7
Lung ca. A549	17.2	Brain (Amygdala) Pool	5.0
Lung ca. NCI-H526	3.3	Brain (cerebellum)	16.4
Lung ca. NCI-H23	47.0	Brain (fetal)	20.9
Lung ca. NCI-H460	48.6	Brain (Hippocampus) Pool	9 8
Lung ca. HOP-62	12.6	Cerebral Cortex Pool	8.5
Lung ca. NCI-H522	26.4	Brain (Substantia nigra)	9.0
		Pool
Liver	0.0	Brain (Thalamus) Pool	16.2
Fetal Liver	14.7	Brain (whole)	5.8
Liver ca. HepG2	12.1	Spinal Cord Pool	9.3
Kidney Pool	49.7	Adrenal Gland	13.4
Fetal Kidney	25.3	Pituitary gland Pool	5.3
Renal ca. 786-0	16.7	Salivary Gland	4.4
Renal ca. A498	5.2	Thyroid (female)	2.4
Renal ca. ACHN	10.5	Pancreatic ca. CAPAN2	30.8
Renal ca. UO-31	6.7	Pancreas Pool	18.4

[0745]

TABLE PD
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4320, Run		Ag4320, Run
Tissue Name	182392272	Tissue Name	182392272
Secondary Th1 act	13.7	HUVEC IL-1beta	3.1
Secondary Th2 act	15.8	HUVEC IFN gamma	4.5
Secondary Tr1 act	31.9	HUVEC TNF alpha + IFN	2.5
		gamma
Secondary Th1 rest	2.5	HUVEC TNF alpha + IL4	6.2
Secondary Th2 rest	9.9	HUVEC IL-11	3.1
Secondary Tr1 rest	23.2	Lung Microvascular EC	11.3
		none
Primary Th1 act	19.5	Lung Microvascular EC	6.0
		TNF alpha + IL-1beta
Primary Th2 act	20.7	Microvascular Dermal EC	2.8
		none
Primary Tr1 act	20.4	Microsvasular Dermal EC	5.1
		TNF alpha + IL-1beta
Primary Th1 rest	18.4	Bronchial epithelium	7.0
		TNF alpha + IL1beta
Primary Th2 rest	12.5	Small airway epithelium	1.1
		none
Primary Tr1 rest	13.8	Small airway epithelium	4.0
		TNF alpha + IL-1beta
CD45RA CD4 lymphocyte	2.8	Coronery artery SMC rest	0.0
act
CD45RO CD4 lymphocyte	21.0	Coronery artery SMC	0.0
act		TNF alpha + IL-1beta
CD8 lymphocyte act	34.4	Astrocytes rest	1.5
Secondary CD8 lymphocyte	21.5	Astrocytes TNF alpha + IL-	2.4
rest		1beta
Secondary CD8 lymphocyte	8.8	KU-812 (Basophil) rest	11.6
act
CD4 lymphocyte none	18.8	KU-812 (Basophil)	23.3
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	15.5	CCD1106 (Keratinocytes)	3.5
CH11		none
LAK cells rest	25.0	CCD1106 (Keratinocytes)	3.0
		TNF alpha + IL-1beta
LAK cells IL-2	8.9	Liver cirrhosis	13.2
LAK cells IL-2 + IL-12	17.6	NCI-H292 none	9.4
LAK cells IL-2 + IFN gamma	17.4	NCI-H292 IL-4	11.2
LAK cells IL-2 + IL-18	10.4	NCI-H292 IL-9	6.9
LAK cells PMA/ionomycin	21.5	NCI-H292 IL-13	6.8
NK Cells IL-2 rest	26.2	NCI-H292 IFN gamma	5.4
Two Way MLR 3 day	23.2	HPAEC none	0.7
Two Way MLR 5 day	6.4	HPAEC TNF alpha +	19.1
		IL-1beta
Two Way MLR 7 day	16.0	Lung fibroblast none	3.4
PBMC rest	30.8	Lung fibroblast	2.4
		TNF alpha + IL-1beta
PBMC PWM	15.2	Lung fibroblast IL-4	1.4
PBMC PHA-L	13.3	Lung fibroblast IL-9	4.6
Ramos (B cell) none	17.7	Lung fibroblast IL-13	10.1
Ramos (B cell) ionomycin	12.0	Lung fibroblast IFN gamma	4.8
B lymphocytes PWM	11.8	Dermal fibroblast CCD1070	8.8
		rest
B lymphocytes CD40L and	31.0	Dermal fibroblast CCD1070	15.1
IL-4		TNF alpha
EOL-1 dbcAMP	21.6	Dermal fibroblast CCD1070	0.0
		IL-1beta
EOL-1 dbcAMP	31.2	Dermal fibroblast IFN	2.6
PMA/ionomycin		gamma
Dendritic cells none	8.9	Dermal fibroblast IL-4	8.3
Dendritic cells LPS	3.5	Dermal Fibroblasts rest	1.3
Dendritic cells anti-CD40	8.0	Neutrophils TNFa + LPS	12.7
Monocytes rest	70.7	Neutrophils rest	17.8
Monocytes LPS	25.9	Colon	9.5
Macrophages rest	14.9	Lung	9.7
Macrophages LPS	8.7	Thymus	99.3
HUVEC none	3.0	Kidney	100.0
HUVEC starved	5.9

[0746] CNS_neurodegeneration_v1.0 Summary: Ag4320 This panel confirms the presence of this gene in the brain. Please see Panel 1.4 for discussion of this gene in the central nervous system.

[0747] General_screening_panel_v1.4 Summary: Ag4320 This gene is widely expressed in this panel, with highest expression in a breast cancer cell line (CT=30.2). Prominent levels of expression are also seen in brain, lung, and ovarian cancer cell lines. This widespread expression suggests that this gene is involved in cell growth. Therapeutic modulation of the expression or function of this protein may be useful in the treatment of these cancers.

[0748] This gene is also expressed at low but significant levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum 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.

[0749] Among tissues with metabolic function, this gene is expressed at low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, skeletal muscle, fetal liver and adult and fetal heart. This expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0750] Panel 4.1D Summary: Ag4320 Highest expression is seen in the thymus and kidney (CTs=31). Low but significant levels of expression are also seen in many other samples on this panel including 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.

Q. CG105796-01: Novel Neurotransmitter-gated Ion-channel

[0751] Expression of gene CG105796-01 was assessed using the primer-probe set Ag4307, described in Table QA. Results of the RTQ-PCR runs are shown in Table QB.

TABLE QA
Probe Name Ag4307
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gagctgagacctctccttgaag-3′	22	1000	137
Probe	TET-5′-agaccaggagccagctgccagct-3′-TAMRA	23	1026	138
Reverse	5′-caagagtgcaaggtttctctga-3′	22	1069	139

[0752]

TABLE QB
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4307, Run		Ag4307, Run
Tissue Name	182243415	Tissue Name	182243415
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 + IFN	0.1
		gamma
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	0.1
Secondary Th2 rest	0.1	HUVEC IL-11	0.0
Secondary Tr1 rest	0.0	Lung Microvascular EC none	0.4
Primary Th1 act	0.0	Lung Microvascular EC	0.1
		TNF alpha + IL-1beta
Primary Th2 act	0.0	Microvascular Dermal EC	0.0
		none
Primary Tr1 act	0.0	Microsvasular Dermal EC	0.0
		TNF alpha + IL-1beta
Primary Th1 rest	0.1	Bronchial epithelium	0.0
		TNF alpha + IL1beta
Primary Th2 rest	0.1	Small airway epithelium none	0.0
Primary Tr1 rest	0.2	Small airway epithelium	0.0
		TNF alpha + IL-1beta
CD45RA CD4 lymphocyte	0.1	Coronery artery SMC rest	0.0
act
CD45RO CD4 lymphocyte	0.1	Coronery artery SMC	0.0
act		TNF alpha + IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	0.0
Secondary CD8 lymphocyte	0.1	Astrocytes TNF alpha + IL-	0.0
rest		1beta
Secondary CD8 lymphocyte	0.2	KU-812 (Basophil) rest	0.0
act
CD4 lymphocyte none	0.2	KU-812 (Basophil)	0.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	0.2	CCD1106 (Keratinocytes)	0.0
CD95 CH11		none
LAK cells rest	0.0	CCD1106 (Keratinocytes)	0.0
		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	0.1	NCI-H292 IL-4	0.0
gamma
LAK cells IL-2 + IL-18	0.1	NCI-H292 IL-9	0.0
LAK cells PMA/ionomycin	0.0	NCI-H292 IL-13	0.0
NK Cells IL-2 rest	2.8	NCI-H292 IFN gamma	0.0
Two Way MLR 3 day	0.3	HPAEC none	0.1
Two Way MLR 5 day	0.0	HPAEC TNF alpha +	0.1
		IL-1beta
Two Way MLR 7 day	0.0	Lung fibroblast none	0.0
PBMC rest	0.1	Lung fibroblast TNF alpha +	0.2
		IL-1beta
PBMC PWM	0.0	Lung fibroblast IL-4	0.1
PBMC PHA-L	0.0	Lung fibroblast IL-9	0.0
Ramos (B cell) none	0.0	Lung fibroblast IL-13	0.1
Ramos (B cell) ionomycin	0.0	Lung fibroblast IFN gamma	0.0
B lymphocytes PWM	0.0	Dermal fibroblast CCD1070	0.1
		rest
B lymphocytes CD40L and	0.1	Dermal fibroblast CCD1070	0.6
IL-4		TNF alpha
EOL-1 dbcAMP	1.6	Dermal fibroblast CCD1070	0.0
		IL-1beta
EOL-1 dbcAMP	0.1	Dermal fibroblast IFN	0.1
PMA/ionomycin		gamma
Dendritic cells none	0.0	Dermal fibroblast IL-4	0.5
Dendritic cells LPS	0.1	Dermal Fibroblasts rest	1.0
Dendritic cells anti-CD40	0.1	Neutrophils TNFa + LPS	1.1
Monocytes rest	0.7	Neutrophils rest	2.1
Monocytes LPS	0.2	Colon	2.5
Macrophages rest	0.0	Lung	3.6
Macrophages LPS	0.1	Thymus	14.0
HUVEC none	0.0	Kidney	100.0
HUVEC starved	0.1

[0753] Panel 4.1D Summary: Ag4307 Highest expression of this gene is seen in kidney (CT=27.9). Thus, expression of this gene could be used to differentiate the kidney derived sample from other samples on this panel and as a marker of kidney tissue. In addition, therapeutic targeting of the expression or function of this gene may modulate kidney function and be important in the treatment of inflammatory or autoimmune diseases that affect the kidney, including lupus and glomerulonephritis.

R. CG106002-01: Carboxyl-Terminal PDZ Ligand of Neuronal Nitric Oxide Synthase

[0754] Expression of gene CG 106002-01 was assessed using the primer-probe set Ag4315, described in Table RA. Results of the RTQ-PCR runs are shown in Tables RB, RC and RD.

TABLE RA
Probe Name Ag4315
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gaccccatctacaggatcttct-3′	22	718	141
Probe	TET-5′-tgtctctcatgattcccaagacttga-3′-TAMRA	26	741	142
Reverse	5′-catctcgagcgatatagctgaa-3′	22	772	143

[0755]

TABLE RB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4315, Run		Ag4315, Run
Tissue Name	224074858	Tissue Name	224074858
AD 1 Hippo	12.3	Control (Path) 3 Temporal	2.1
		Ctx
AD 2 Hippo	34.2	Control (Path) 4 Temporal	25.7
		Ctx
AD 3 Hippo	7.6	AD 1 Occipital Ctx	14.9
AD 4 Hippo	5.6	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 hippo	90.8	AD 3 Occipital Ctx	3.4
AD 6 Hippo	57.4	AD 4 Occipital Ctx	12.8
Control 2 Hippo	38.2	AD 5 Occipital Ctx	17.6
Control 4 Hippo	3.5	AD 6 Occipital Ctx	46.7
Control (Path) 3 Hippo	3.1	Control 1 Occipital Ctx	0.7
AD 1 Temporal Ctx	9.5	Control 2 Occipital Ctx	55.1
AD 2 Temporal Ctx	26.1	Control 3 Occipital Ctx	12.3
AD 3 Temporal Ctx	4.5	Control 4 Occipital Ctx	2.7
AD 4 Temporal Ctx	15.3	Control (Path) 1 Occipital	76.3
		Ctx
AD 5 Inf Temporal Ctx	100.0	Control (Path) 2 Occipital	9.4
		Ctx
AD 5 SupTemporal Ctx	45.1	Control (Path) 3 Occipital	1.0
		Ctx
AD 6 Inf Temporal Ctx	61.6	Control (Path) 4 Occipital	16.2
		Ctx
AD 6 Sup Temporal Ctx	59.5	Control 1 Parietal Ctx	2.3
Control 1 Temporal Ctx	2.0	Control 2 Parietal Ctx	35.1
Control 2 Temporal Ctx	28.3	Control 3 Parietal Ctx	13.9
Control 3 Temporal Ctx	13.3	Control (Path) 1 Parietal	54.3
		Ctx
Control 4 Temporal Ctx	4.4	Control (Path) 2 Parietal	23.0
		Ctx
Control (Path) 1 Temporal Ctx	64.6	Control (Path) 3 Parietal	0.8
		Ctx
Control (Path) 2 Temporal Ctx	39.8	Control (Path) 4 Parietal	42.9
		Ctx

[0756]

TABLE RC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4315, Run		Ag4315, Run
Tissue Name	222364258	Tissue Name	222364258
Adipose	4.6	Renal ca. TK-10	31.9
Melanoma* Hs688(A).T	0.1	Bladder	7.6
Melanoma* Hs688(B).T	0.3	Gastric ca. (liver met.)	38.4
		NCI-N87
Melanoma* M14	0.9	Gastric ca. KATO III	22.5
Melanoma* LOXIMVI	0.2	Colon ca. SW-948	9.4
Melanoma* SK-MEL-5	32.1	Colon ca. SW480	23.3
Squamous cell carcinoma	2.6	Colon ca.* (SW480 met)	9.3
SCC-4		SW620
Testis Pool	3.6	Colon ca. HT29	5.7
Prostate ca.* (bone met) PC-3	5.9	Colon ca. HCT-116	19.8
Prostate Pool	3.4	Colon ca. CaCo-2	17.8
Placenta	5.2	Colon cancer tissue	8.1
Uterus Pool	1.0	Colon ca. SW1116	1.9
Ovarian ca. OVCAR-3	4.8	Colon ca. Colo-205	6.6
Ovarian ca. SK-OV-3	24.0	Colon ca. SW-48	5.6
Ovarian ca. OVCAR-4	1.6	Colon Pool	3.8
Ovarian ca. OVCAR-5	58.6	Small Intestine Pool	3.9
Ovarian ca. IGROV-1	23.7	Stomach Pool	3.3
Ovarian ca. OVCAR-8	8.0	Bone Marrow Pool	2.4
Ovary	7.3	Fetal Heart	3.6
Breast ca. MCF-7	28.9	Heart Pool	2.8
Breast ca. MDA-MB-231	10.9	Lymph Node Pool	6.6
Breast ca. BT 549	2.7	Fetal Skeletal Muscle	0.7
Breast ca. T47D	92.7	Skeletal Muscle Pool	0.6
Breast ca. MDA-N	8.0	Spleen Pool	1.2
Breast Pool	6.5	Thymus Pool	3.3
Trachea	15.6	CNS cancer (glio/astro)	9.5
		U87-MG
Lung	0.9	CNS cancer (glio/astro) U-	1.0
		118-MG
Fetal Lung	9.6	CNS cancer (neuro; met)	0.2
		SK-N-AS
Lung ca. NCI-N417	6.4	CNS cancer (astro) SF-539	0.7
Lung ca. LX-1	6.1	CNS cancer (astro) SNB-75	6.2
Lung ca. NCI-H146	10.7	CNS cancer (glio) SNB-19	24.5
Lung ca. SHP-77	3.8	CNS cancer (glio) SF-295	17.8
Lung ca. A549	0.1	Brain (Amygdala) Pool	16.7
Lung ca. NCI-H526	5.9	Brain (cerebellum)	100.0
Lung ca. NCI-H23	2.1	Brain (fetal)	35.8
Lung ca. NCI-H460	1.3	Brain (Hippocampus) Pool	18.9
Lung ca. HOP-62	0.5	Cerebral Cortex Pool	24.7
Lung ca. NCI-H522	3.3	Brain (Substantia nigra)	21.2
		Pool
Liver	5.2	Brain (Thalamus) Pool	34.2
Fetal Liver	13.8	Brain (whole)	28.5
Liver ca. HepG2	21.3	Spinal Cord Pool	11.7
Kidney Pool	9.4	Adrenal Gland	10.9
Fetal Kidney	15.5	Pituitary gland Pool	1.9
Renal ca. 786-0	1.8	Salivary Gland	12.7
Renal ca. A498	3.7	Thyroid (female)	0.6
Renal ca. ACHN	5.8	Pancreatic ca. CAPAN2	23.5
Renal ca. UO-31	3.8	Pancreas Pool	5.1

[0757]

TABLE RD
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4315, Run		Ag4315, Run
Tissue Name	182244231	Tissue Name	182244231
Secondary Th1 act	1.1	HUVEC IL-1 beta	36.1
Secondary Th2 act	0.0	HUVEC IFN gamma	29.3
Secondary Tr1 act	0.0	HUVEC TNF alpha + IFN	11.5
		gamma
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	9.0
Secondary Th2 rest	0.0	HUVEC IL-11	29.1
Secondary Tr1 rest	0.0	Lung Microvascular EC	30.6
		none
Primary Th1 act	0.0	Lung Microvascular EC	13.1
		TNF alpha + IL-1 beta
Primary Th2 act	0.9	Microvascular Dermal EC	61.1
		none
Primary Tr1 act	1.8	Microsvasular Dermal EC	11.0
		TNF alpha + IL-1 beta
Primary Th1 rest	0.0	Bronchial epithelium	4.0
		TNF alpha + IL1 beta
Primary Th2 rest	0.0	Small airway epithelium	2.0
		none
Primary Tr1 rest	0.0	Small airway epithelium	4.6
		TNF alpha + IL-1 beta
CD45RA CD4 lymphocyte act	3.3	Coronery artery SMC rest	0.0
CD45RO CD4 lymphocyte act	0.9	Coronery artery SMC	0.0
		TNF alpha + IL-1 beta
CD8 lymphocyte act	0.0	Astrocytes rest	55.1
Secondary CD8 lymphocyte	3.4	Astrocytes TNF alpha + IL-	11.9
rest		1 beta
Secondary CD8 lymphocyte	0.0	KU-812 (Basophil) rest	8.0
act
CD4 lymphocyte none	0.0	KU-812 (Basophil)	13.8
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	0.0	CCD1106 (Keratinocytes)	5.8
CH11		none
LAK cells rest	1.5	CCD1106 (Keratinocytes)	11.4
		TNF alpha + IL-1 beta
LAK cells IL-2	2.3	Liver cirrhosis	28.7
LAK cells IL-2 + IL-12	0.0	NCI-H292 none	33.2
LAK cells IL-2 + IFN gamma	0.0	NCI-H292 IL-4	29.3
LAK cells IL-2 + IL-18	0.9	NCI-H292 IL-9	82.4
LAK cells PMA/ionomycin	2.1	NCI-H292 IL-13	33.9
NK Cells IL-2 rest	0.0	NCI-H292 IFN gamma	36.9
Two Way MLR 3 day	1.9	HPAEC none	58.6
Two Way MLR 5 day	2.7	HPAEC TNF alpha + IL-1	15.3
		beta
Two Way MLR 7 day	1.8	Lung fibroblast none	0.0
PBMC rest	0.9	Lung fibroblast TNF alpha +	0.0
		IL-1 beta
PBMC PWM	1.9	Lung fibroblast IL-4	1.3
PBMC PHA-L	1.9	Lung fibroblast IL-9	1.6
Ramos (B cell) none	0.0	Lung fibroblast IL-13	3.9
Ramos (B cell) ionomycin	0.0	Lung fibroblast IFN	2.1
		gamma
B lymphocytes PWM	0.8	Dermal fibroblast	0.0
		CCD1070 rest
B lymphocytes CD40L and	3.6	Dermal fibroblast	3.4
IL-4		CCD1070 TNF alpha
EOL-1 dbcAMP	51.8	Dermal fibroblast	2.3
		CCD1070 IL-1 beta
EOL-1 dbcAMP	4.7	Dermal fibroblast IFN	5.4
PMA/ionomycin		gamma
Dendritic cells none	8.0	Dermal fibroblast IL-4	0.0
Dendritic cells LPS	2.0	Dermal Fibroblasts rest	7.3
Dendritic cells anti-CD40	0.0	Neutrophils TNFa + LPS	1.7
Monocytes rest	0.0	Neutrophils rest	1.8
Monocytes LPS	4.9	Colon	27.2
Macrophages rest	100.0	Lung	17.0
Macrophages LPS	6.6	Thymus	18.9
HUVEC none	28.5	Kidney	94.6
HUVEC starved	20.0

[0758] CNS_neurodegeneration_v1.0 Summary: Ag4315 This panel confirms the expression of this gene at moderate levels in the brain in an independent group of individuals. This gene is upregulated in the temporal cortex of Alzheimer's disease patients when compared with non-demented controls. Therefore, therapeutic modulation fo the expression or function of this gene may slow or stop the progression of Alzheimer's disease.

[0759] General_screening_panel_v1.4 Summary: Ag4315 Highest expression of this gene is seen in the cerebellum (CT=28). Moderate levels of expression are seen throughout the CNS. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurological disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.

[0760] Prominent levels of expression are seen in clusters of cell lines derived from breast and ovarian cancer cell lines. Moderate levels of expression are also detected in samples from pancreatic, brain, renal, lung, melanoma, colon and gastric cancers. Thus, expression of this gene could be used as a marker of breast and ovarian cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of these cancers.

[0761] 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 heart and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0762] Panel 4.1D Summary: Ag4315 Highest expression is seen in resting macrophages (CT=32.4). Low but significant levels of expression are seen in kidney, untreated HPAECs, untreated astrocytes, and treated and untreated NCI-H292 cells. In addition, this protein encoded by this gene is down regulated in macrophages after LPS stimulation. Therefore, this gene product may respond to inflammatory stimuli and become down regulated after 12-24 hr exposure. Thus, therapeutics designed against this putative protein may reduce or inhibit inflammation in diseases such as asthma, IBD, psoriasis, arthritis and allergy. Furthermore, agonistic therapeutics designed with this protein product may stimulate/provoke the immune response and improve the efficacy of vaccines and antiviral or antibacterial treatments.

S. CG106868-01: Amyloid Beta A4 Precursor Protein-Binding Family B Member 2

[0763] Expression of gene CG106868-01 was assessed using the primer-probe set Ag4327, described in Table SA. Results of the RTQ-PCR runs are shown in Tables SB, SC and SD.

TABLE SA
Probe Name Ag4327
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-tatactgatgccaacagccaat-3′	22	269	144
Probe	TET-5′-tgtcaaccaacaggttcaattttatga-3′-TAMRA	27	293	145
Reverse	5′-aaataggatggcgagtttgtg-3′	21	330	146

[0764]

TABLE SB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4327, Run		Ag4327, Run
Tissue Name	224344076	Tissue Name	224344076
AD 1 Hippo	12.8	Control (Path) 3 Temporal	6.0
		Ctx
AD 2 Hippo	24.1	Control (Path) 4 Temporal	28.1
		Ctx
AD 3 Hippo	8.2	AD 1 Occipital Ctx	20.0
AD 4 Hippo	6.8	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 Hippo	92.0	AD 3 Occipital Ctx	8.7
AD 6 Hippo	54.7	AD 4 Occipital Ctx	17.3
Control 2 Hippo	21.9	AD 5 Occipital Ctx	32.3
Control 4 Hippo	9.2	AD 6 Occipital Ctx	26.4
Control (Path) 3 Hippo	9.5	Control 1 Occipital Ctx	5.6
AD 1 Temporal Ctx	18.4	Control 2 Occipital Ctx	48.6
AD 2 Temporal Ctx	26.8	Control 3 Occipital Ctx	16.2
AD 3 Temporal Ctx	6.9	Control 4 Occipital Ctx	6.8
AD 4 Temporal Ctx	21.0	Control (Path) 1 Occipital	84.1
		Ctx
AD 5 Inf Temporal Ctx	100.0	Control (Path) 2 Occipital	14.7
		Ctx
AD 5 Sup Temporal Ctx	50.3	Control (Path) 3 Occipital	5.4
		Ctx
AD 6 Inf Temporal Ctx	72.7	Control (Path) 4 Occipital	19.6
		Ctx
AD 6 Sup Temporal Ctx	57.4	Control 1 Parietal Ctx	7.4
Control 1 Temporal Ctx	5.4	Control 2 Parietal Ctx	47.3
Control 2 Temporal Ctx	31.9	Control 3 Parietal Ctx	15.5
Control 3 Temporal Ctx	17.8	Control (Path) 1 Parietal Ctx	68.3
Control 3 Temporal Ctx	6.0	Control (Path) 2 Parietal Ctx	29.1
Control (Path) 1 Temporal	42.3	Control (Path) 3 Parietal Ctx	5.4
Ctx
Control (Path) 2 Temporal	28.9	Control (Path) 4 Parietal Ctx	37.9
Ctx

[0765]

TABLE SC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4327, Run		Ag4327, Run
Tissue Name	222550477	Tissue Name	222550477
Adipose	20.9	Renal ca. TK-10	13.7
Melanoma* Hs688(A).T	32.1	Bladder	18.0
Melanoma* Hs688(B).T	29.5	Gastric ca. (liver met.) NCI-	24.3
		N87
Melanoma* M14	0.7	Gastric ca. KATO III	46.0
Melanoma* LOXIMVI	44.4	Colon ca. SW-948	9.5
Melanoma* SK-MEL-5	9.9	Colon ca. SW480	61.6
Squamous cell carcinoma	6.4	Colon ca.* (SW480 met)	26.4
SCC-4		SW620
Testis Pool	6.7	Colon ca. HT29	2.4
Prostate ca.* (bone met)	47.3	Colon ca. HCT-116	51.1
PC-3
Prostate Pool	5.1	Colon ca. CaCo-2	25.2
Placenta	4.2	Colon cancer tissue	15.1
Uterus Pool	5.3	Colon ca. SW1116	3.1
Ovarian ca. OVCAR-3	14.5	Colon ca. Colo-205	1.8
Ovarian ca. SK-OV-3	26.6	Colon ca. SW-48	11.7
Ovarian ca. OVCAR-4	4.9	Colon Pool	12.9
Ovarian ca. OVCAR-5	30.4	Small Intestine Pool	12.5
Ovarian ca. IGROV-1	13.9	Stomach Pool	11.0
Ovarian ca. OVCAR-8	19.2	Bone Marrow Pool	6.0
Ovary	17.3	Fetal Heart	5.8
Breast ca. MCF-7	100.0	Heart Pool	7.2
Breast ca. MDA-MB-231	61.6	Lymph Node Pool	15.4
Breast ca. BT 549	12.9	Fetal Skeletal Muscle	6.7
Breast ca. T47D	52.1	Skeletal Muscle Pool	7.0
Breast ca. MDA-N	6.8	Spleen Pool	14.0
Breast Pool	11.8	Thymus Pool	11.0
Trachea	13.3	CNS cancer (glio/astro)	46.0
		U87-MG
Lung	5.4	CNS cancer (glio/astro) U-	16.5
		118-MG
Fetal Lung	41.8	CNS cancer (neuro;met) SK-	5.0
		N-AS
Lung ca. NCI-N417	1.6	CNS cancer (astro) SF-539	10.3
Lung ca. LX-1	22.5	CNS cancer (astro) SNB-75	29.3
Lung ca. NCI-H146	20.3	CNS cancer (glio) SNB-19	14.7
Lung ca. SHP-77	8.2	CNS cancer (glio) SF-295	60.7
Lung ca. A549	9.2	Brain (Amygdala) Pool	20.9
Lung ca. NCI-H526	34.6	Brain (cerebellum)	6.3
Lung ca. NCI-H23	31.2	Brain (fetal)	27.4
Lung ca. NCI-H460	10.7	Brain (Hippocampus) Pool	21.5
Lung ca. HOP-62	28.1	Cerebral Cortex Pool	21.8
Lung ca. NCI-H522	96.6	Brain (Substantia nigra)	15.8
		Pool
Liver	1.1	Brain (Thalamus) Pool	29.9
Fetal Liver	8.8	Brain (whole)	20.6
Liver ca. HepG2	7.3	Spinal Cord Pool	27.7
Kidney Pool	35.6	Adrenal Gland	7.2
Fetal Kidney	17.6	Pituitary gland Pool	2.8
Renal ca. 786-0	30.1	Salivary Gland	1.9
Renal ca. A498	6.8	Thyroid (female)	11.2
Renal ca. ACHN	13.9	Pancreatic ca. CAPAN2	27.9
Renal ca. UO-31	20.4	Pancreas Pool	15.9

[0766]

TABLE SD
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4327, Run		Ag4327, Run
Tissue Name	183714654	Tissue Name	183714654
Secondary Th1 act	73.7	HUVEC IL-1 beta	66.4
Secondary Th2 act	13.4	HUVEC IFN gamma	56.6
Secondary Tr1 act	18.6	HUVEC TNF alpha + IFN	35.6
		gamma
Secondary Th1 rest	1.3	HUVEC TNF alpha + IL4	52.1
Secondary Th2 rest	0.4	HUVEC IL-11	27.7
Secondary Tr1 rest	0.3	Lung Microvascular EC	81.8
		none
Primary Th1 act	3.3	Lung Microvascular EC	56.6
		TNF alpha + IL-1 beta
Primary Th2 act	0.4	Microvascular Dermal EC	40.6
		none
Primary Tr1 act	0.9	Microsvasular Dermal EC	28.9
		TNF alpha + IL-1 beta
Primary Th1 rest	0.1	Bronchial epithelium	20.7
		TNF alpha + IL1 beta
Primary Th2 rest	0.0	Small airway epithelium	5.9
		none
Primary Tr1 rest	0.0	Small airway epithelium	16.4
		TNF alpha + IL-1 beta
CD45RA CD4 lymphocyte	11.8	Coronery artery SMC rest	27.4
act
CD45RO CD4 lymphocyte	0.1	Coronery artery SMC	43.2
act		TNF alpha + IL-1 beta
CD8 lymphocyte act	0.2	Astrocytes rest	11.5
Secondary CD8 lymphocyte	0.0	Astrocytes TNF alpha + IL-	12.5
rest		1 beta
Secondary CD8 lymphocyte	0.4	KU-812 (Basophil) rest	0.0
act
CD4 lymphocyte none	0.0	KU-812 (Basophil)	0.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	0.1	CCD1106 (Keratinocytes)	21.0
CH11		none
LAK cells rest	1.3	CCD1106 (Keratinocytes)	24.8
		TNF alpha + IL-1 beta
LAK cells IL-2	2.1	Liver cirrhosis	9.9
LAK cells IL-2 + IL-12	2.2	NCI-H292 none	7.4
LAK cells IL-2 + IFN gamma	1.6	NCI-H292 IL-4	15.6
LAK cells IL-2 + IL-18	2.1	NCI-H292 IL-9	9.1
LAK cells PMA/ionomycin	0.4	NCI-H292 IL-13	16.6
NK Cells IL-2 rest	1.5	NCI-H292 IFN gamma	9.0
Two Way MLR 3 day	2.4	HPAEC none	43.5
Two Way MLR 5 day	3.6	HPAEC TNF alpha + IL-1	100.0
		beta
Two Way MLR 7 day	3.7	Lung fibroblast none	15.6
PBMC rest	0.2	Lung fibroblast TNF alpha +	10.0
		IL-1 beta
PBMC PWM	2.1	Lung fibroblast IL-4	9.9
PBMC PHA-L	0.7	Lung fibroblast IL-9	27.9
Ramos (B cell) none	27.0	Lung fibroblast IL-13	11.9
Ramos (B cell) ionomycin	47.3	Lung fibroblast IFN gamma	22.1
B lymphocytes PWM	1.6	Dermal fibroblast CCD1070	17.8
		rest
B lymphocytes CD40L and	1.1	Dermal fibroblast CCD1070	14.2
IL-4		TNF alpha
EOL-1 dbcAMP	0.8	Dermal fibroblast CCD1070	17.6
		IL-1 beta
EOL-1 dbcAMP	3.4	Dermal fibroblast IFN	10.7
PMA/ionomycin		gamma
Dendritic cells none	8.0	Dermal fibroblast IL-4	27.0
Dendritic cells LPS	1.2	Dermal Fibroblasts rest	13.9
Dendritic cells anti-CD40	3.8	Neutrophils TNFa + LPS	0.0
Monocytes rest	0.2	Neutrophils rest	1.7
Monocytes LPS	1.1	Colon	1.8
Macrophages rest	10.3	Lung	23.3
Macrophages LPS	3.4	Thymus	15.6
HUVEC none	49.7	Kidney	25.3
HUVEC starved	57.4

[0767] CNS_neurodegeneration_v1.0 Summary: Ag4237 This panel confirms the expression of this gene at moderate levels in the brain in an independent group of individuals. This gene appears to be upregulated in the temporal cortex of Alzheimer's disease patients when compared with non-demented controls. Thus, based on the homology of this protein to Abeta protein binding family, therapeutic modulation of this gene or gene product may slow or stop the progression of Alzheimer's disease.

[0768] General_screening_panel_v1.4 Summary: Ag4237 Highest expression of this gene is seen in a breast cancer cell line (CT=27.2). High levels of expression are also seen in cell lines derived from brain, lung, and colon cancers, with moderate levels of expression in all the cancer cell lines on this panel. In addition, higher levels of expression are seen in fetal lung and liver (CTs=28.5-30.5) when compared to expression in the adult tissues (CTs=31.5-33.5). Thus, expression of this gene could be used to differentiate between the adult and fetal sources of these tissues. This expression profile also suggests a role for this gene product in cell survival and proliferation. Therefore, modulation of this gene product may be useful in the treatment of cancer.

[0769] 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 function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0770] This gene is also expressed at moderate levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum 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.

[0771] Panel 4.1D Summary: Ag4237 Highest expression of this gene is seen in TNF-a and IL-1b treated HPAECs (CT=29.2). This gene is also expressed at moderate to low 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.

T. CG106988-01: Calreticulin

[0772] Expression of gene CG106988-01 was assessed using the primer-probe set Ag4333, described in Table TA. Results of the RTQ-PCR runs are shown in Table TB.

TABLE TA
Probe Name Ag4333
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ataaaggtctgcaaaccactca-3′	22	260	147
Probe	TET-5′-attctatgccatctctgcacgcttca-3′-TAMRA	26	291	148
Reverse	5′-ccagagttttccctttattgct-3′	22	325	149

[0773]

TABLE TB
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4333, Run		Ag4333, Run
Tissue Name	222556384	Tissue Name	222556384
Adipose	0.0	Renal ca. TK-10	0.1
Melanoma* Hs688(A).T	0.2	Bladder	0.0
Melanoma* Hs688(B).T	0.0	Gastric ca. (liver met.) NCI-	0.7
		N87
Melanoma* M14	0.1	Gastric ca. KATO III	0.0
Melanoma* LOXIMVI	0.2	Colon ca. SW-948	0.1
Melanoma* SK-MEL-5	0.8	Colon ca. SW480	1.3
Squamous cell carcinoma	0.0	Colon ca.* (SW480 met)	0.3
SCC-4		SW620
Testis Pool	100.0	Colon ca. HT29	0.2
Prostate ca.* (bone met)	0.7	Colon ca. HCT-116	0.2
PC-3
Prostate Pool	0.0	Colon ca. CaCo-2	0.6
Placenta	0.2	Colon cancer tissue	0.1
Uterus Pool	0.0	Colon ca. SW1116	0.2
Ovarian ca. OVCAR-3	0.1	Colon ca. Colo-205	0.2
Ovarian ca. SK-OV-3	0.2	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	0.0	Colon Pool	0.0
Ovarian ca. OVCAR-5	0.1	Small Intestine Pool	0.2
Ovarian ca. IGROV-1	0.1	Stomach Pool	0.0
Ovarian ca. OVCAR-8	0.0	Bone Marrow Pool	0.0
Ovary	0.0	Fetal Heart	0.0
Breast ca. MCF-7	0.6	Heart Pool	0.0
Breast ca. MDA-MB-231	0.4	Lymph Node Pool	0.0
Breast ca. BT 549	0.1	Fetal Skeletal Muscle	0.1
Breast ca. T47D	0.7	Skeletal Muscle Pool	0.1
Breast ca. MDA-N	0.1	Spleen Pool	0.1
Breast Pool	0.0	Thymus Pool	0.0
Trachea	0.7	CNS cancer (glio/astro) U87-	0.3
		MG
Lung	0.0	CNS cancer (glio/astro) U-	0.1
		118-MG
Fetal Lung	0.0	CNS cancer (neuro;met) SK-	0.3
		N-AS
Lung ca. NCI-N417	0.1	CNS cancer (astro) SF-539	0.1
Lung ca. LX-1	0.5	CNS cancer (astro) SNB-75	0.5
Lung ca. NCI-H146	0.1	CNS cancer (glio) SNB-19	0.3
Lung ca. SHP-77	1.4	CNS cancer (glio) SF-295	0.1
Lung ca. A549	0.5	Brain (Amygdala) Pool	0.0
Lung ca. NCI-H526	0.1	Brain (cerebellum)	0.2
Lung ca. NCI-H23	1.6	Brain (fetal)	0.1
Lung ca. NCI-H460	0.0	Brain (Hippocampus) Pool	0.2
Lung ca. HOP-62	0.0	Cerebral Cortex Pool	0.1
Lung ca. NCI-H522	1.6	Brain (Substantia nigra) Pool	0.0
Liver	0.0	Brain (Thalamus) Pool	0.0
Fetal Liver	0.3	Brain (whole)	0.1
Liver ca. HepG2	0.6	Spinal Cord Pool	0.0
Kidney Pool	0.1	Adrenal Gland	0.1
Fetal Kidney	0.2	Pituitary gland Pool	0.0
Renal ca. 786-0	0.4	Salivary Gland	0.0
Renal ca. A498	0.0	Thyroid (female)	0.0
Renal ca. ACHN	0.1	Pancreatic ca. CAPAN2	0.4
Renal ca. UO-31	0.0	Pancreas Pool	0.0

[0774] General_screening_panel_v1.4 Summary: Ag4333 Highest expression of the CG106988-01 gene is detected in testis. Therefore, expression of this gene may be used to distinguish testis from other samples in this panel. In addition, therapeutic modulation of this gene may be beneficial in the treatement diseases that affect testis including fertility and hypogonadism.

[0775] In addition, low expression of this gene is also seen in two colon cancer cell lines, a prostate cancer cell line and a gastric cancer cell lines. Therefore, expression of this gene may be used as a marker to detect the presence of these cancers and therapeutic modulation of this gene product may be beneficial in the treatment of colon, gastric and prostate cancer.

U. CG107363-01: Protein Kinase C Inhibitor

[0776] Expression of gene CG107363-01, representing a full-length physical clone, was assessed using the primer-probe set Ag6926, described in Table UA. Results of the RTQ-PCR runs are shown in Table UB.

TABLE UA
Probe Name Ag6926
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-agtgatattgcaacaatccgt-3′	21	440	150
Probe	TET-5′-ctcattcttgcctactttactctcccactg-3′-TAMRA	30	466	151
Reverse	5′-cataccaccttcaacgctaa-3′	20	503	152

[0777]

TABLE UB
General_screening_panel_v1.6
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag6926, Run		Ag6926, Run
Tissue Name	278700376	Tissue Name	278700376
Adipose	6.7	Renal ca. TK-10	24.0
Melanoma* Hs688(A).T	15.9	Bladder	16.4
Melanoma* Hs688(B).T	16.2	Gastric ca. (liver met.) NCI-	14.9
		N87
Melanoma* M14	86.5	Gastric ca. KATO III	100.0
Melanoma* LOXIMVI	35.8	Colon ca. SW-948	20.6
Melanoma* SK-MEL-5	33.4	Colon ca. SW480	79.0
Squamous cell carcinoma	17.4	Colon ca.* (SW480 met)	59.9
SCC-4		SW620
Testis Pool	14.6	Colon ca. HT29	18.2
Prostate ca.* (bone met)	16.6	Colon ca. HCT-116	59.0
PC-3
Prostate Pool	4.2	Colon ca. CaCo-2	27.7
Placenta	3.6	Colon cancer tissue	14.7
Uterus Pool	3.8	Colon ca. SW1116	13.6
Ovarian ca. OVCAR-3	31.4	Colon ca. Colo-205	18.9
Ovarian ca. SK-OV-3	49.7	Colon ca. SW-48	8.2
Ovarian ca. OVCAR-4	20.4	Colon Pool	7.8
Ovarian ca. OVCAR-5	51.1	Small Intestine Pool	8.5
Ovarian ca. IGROV-1	26.1	Stomach Pool	5.1
Ovarian ca. OVCAR-8	38.2	Bone Marrow Pool	3.8
Ovary	6.0	Fetal Heart	8.4
Breast ca. MCF-7	55.9	Heart Pool	7.7
Breast ca. MDA-MB-231	81.8	Lymph Node Pool	10.6
Breast ca. BT 549	84.7	Fetal Skeletal Muscle	23.5
Breast ca. T47D	24.8	Skeletal Muscle Pool	6.3
Breast ca. MDA-N	35.6	Spleen Pool	7.5
Breast Pool	10.7	Thymus Pool	9.5
Trachea	6.4	CNS cancer (glio/astro) U87-	51.1
		MG
Lung	5.6	CNS cancer (glio/astro) U-	63.7
		118-MG
Fetal Lung	48.6	CNS cancer (neuro; met) SK-	31.0
		N-AS
Lung ca. NCI-N417	23.2	CNS cancer (astro) SF-539	19.6
Lung ca. LX-1	22.5	CNS cancer (astro) SNB-75	54.0
Lung ca. NCI-H146	15.6	CNS cancer (glio) SNB-19	26.6
Lung ca. SHP-77	90.1	CNS cancer (glio) SF-295	55.5
Lung ca. A549	35.4	Brain (Amygdala) Pool	16.0
Lung ca. NCI-H526	10.2	Brain (cerebellum)	43.5
Lung ca. NCI-H23	22.2	Brain (fetal)	42.6
Lung ca. NCI-H460	27.4	Brain (Hippocampus) Pool	27.4
Lung ca. HOP-62	13.0	Cerebral Cortex Pool	24.1
Lung ca. NCI-H522	16.4	Brain (Substantia nigra) Pool	22.7
Liver	1.0	Brain (Thalamus) Pool	24.5
Fetal Liver	16.0	Brain (whole)	33.0
Liver ca. HepG2	7.1	Spinal Cord Pool	18.4
Kidney Pool	14.8	Adrenal Gland	19.9
Fetal Kidney	42.3	Pituitary gland Pool	7.4
Renal ca. 786-0	31.6	Salivary Gland	6.5
Renal ca. A498	14.8	Thyroid (female)	10.1
Renal ca. ACHN	14.8	Pancreatic ca. CAPAN2	22.1
Renal ca. UO-31	17.4	Pancreas Pool	9.4

[0778] General_screening_panel_v1.6 Summary: Ag6926 Highest expression of this gene is seen in a gastric cancer cell line (CT=27.4). This gene is ubiquitously expressed in this panel, with high levels of expression seen in brain, colon, gastric, lung, breast, ovarian, and melanoma cancer cell lines. This expression profile suggests a role for this gene product in cell survival and proliferation. Therefore, modulation of this the expression or activity of this gene product may be useful in the treatment of cancer.

[0779] Among tissues with metabolic function, this gene is expressed at 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 function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0780] This gene is also expressed at moderate levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum 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.

[0781] In addition, this gene is expressed at much higher levels in fetal liver tissue (CT=30) when compared to expression in the adult counterpart (CT=34). Thus, expression of this gene may be used to differentiate between the fetal and adult source of this tissue.

V. CG107363-02 and CG107363-03: Protein Kinase C Inhibitor

[0782] Expression of gene CG107363-02 and variant CG107363-03 was assessed using the primer-probe set Ag4701, described in Table VA. Results of the RTQ-PCR runs are shown in Tables VB, VC and VD. Please note that these genes represent variants of the CG107363-01 gene described in the previous section (Section U) and that CG107363-03 is a full-length physical clone.

TABLE VA
Probe Name Ag4701
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-cctgcatgtctgaagtccatag-3′	22	662	153
Probe	TET-5′tgtcagattatcacgtaacaactgcatga-3′-TAMRA	29	633	154
Reverse	5′-actggatacgctgagtgaagaa-3′	22	589	155

[0783]

TABLE VB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4701, Run		Ag4701, Run
Tissue Name	224710831	Tissue Name	224710831
AD 1 Hippo	12.5	Control (Path) 3 Temporal	7.5
		Ctx
AD 2 Hippo	36.9	Control (Path) 4 Temporal	33.9
		Ctx
AD 3 Hippo	8.1	AD 1 Occipital Ctx	10.2
AD 4 Hippo	9.9	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 Hippo	74.7	AD 3 Occipital Ctx	7.0
AD 6 Hippo	77.9	AD 4 Occipital Ctx	24.0
Control 2 Hippo	43.8	AD 5 Occipital Ctx	51.1
Control 4 Hippo	14.0	AD 6 Occipital Ctx	20.3
Control (Path) 3 Hippo	4.8	Control 1 Occipital Ctx	3.9
AD 1 Temporal Ctx	14.6	Control 2 Occipital Ctx	65.5
AD 2 Temporal Ctx	36.9	Control 3 Occipital Ctx	14.0
AD 3 Temporal Ctx	4.7	Control 4 Occipital Ctx	8.4
AD 4 Temporal Ctx	23.2	Control (Path) 1 Occipital	90.1
		Ctx
AD 5 Inf Temporal Ctx	100.0	Control (Path) 2 Occipital	9.8
		Ctx
AD 5 Sup Temporal Ctx	46.0	Control (Path) 3 Occipital	6.5
		Ctx
AD 6 Inf Temporal Ctx	65.1	Control (Path) 4 Occipital	13.7
		Ctx
AD 6 Sup Temporal Ctx	71.2	Control 1 Parietal Ctx	7.8
Control 1 Temporal Ctx	7.1	Control 2 Parietal Ctx	37.4
Control 2 Temporal Ctx	41.2	Control 3 Parietal Ctx	15.2
Control 3 Temporal Ctx	15.1	Control (Path) 1 Parietal Ctx	79.6
Control 3 Temporal Ctx	9.2	Control (Path) 2 Parietal Ctx	25.7
Control (Path) 1 Temporal	66.4	Control (Path) 3 Parietal Ctx	5.6
Ctx
Control (Path) 2 Temporal	36.1	Control (Path) 4 Parietal Ctx	45.1
Ctx

[0784]

TABLE VC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4701, Run		Ag4701, Run
Tissue Name	222825540	Tissue Name	222825540
Adipose	10.4	Renal ca. TK-10	24.0
Melanoma* Hs688(A).T	22.1	Bladder	15.4
Melanoma* Hs688(B).T	19.3	Gastric ca. (liver met.) NCI-	18.6
		N87
Melanoma* M14	70.7	Gastric ca. KATO III	87.7
Melanoma* LOXIMVI	39.2	Colon ca. SW-948	15.3
Melanoma* SK-MEL-5	36.9	Colon ca. SW480	97.3
Squamous cell carcinoma	20.0	Colon ca.* (SW480 met)	67.4
SCC-4		SW620
Testis Pool	11.9	Colon ca. HT29	25.7
Prostate ca.* (bone met)	29.5	Colon ca. HCT-116	65.5
PC-3
Prostate Pool	5.8	Colon ca. CaCo-2	47.0
Placenta	5.7	Colon cancer tissue	17.8
Uterus Pool	4.5	Colon ca. SW1116	9.6
Ovarian ca. OVCAR-3	29.1	Colon ca. Colo-205	12.8
Ovarian ca. SK-OV-3	28.1	Colon ca. SW-48	8.4
Ovarian ca. OVCAR-4	12.5	Colon Pool	10.6
Ovarian ca. OVCAR-5	34.6	Small Intestine Pool	9.0
Ovarian ca. IGROV-1	25.3	Stomach Pool	5.6
Ovarian ca. OVCAR-8	19.8	Bone Marrow Pool	4.8
Ovary	9.7	Fetal Heart	24.0
Breast ca. MCF-7	35.4	Heart Pool	8.0
Breast ca. MDA-MB-231	77.9	Lymph Node Pool	11.7
Breast ca. BT 549	100.0	Fetal Skeletal Muscle	16.7
Breast ca. T47D	66.9	Skeletal Muscle Pool	15.3
Breast ca. MDA-N	36.9	Spleen Pool	6.0
Breast Pool	10.7	Thymus Pool	8.3
Trachea	11.1	CNS cancer (glio/astro)	42.3
		U87-MG
Lung	3.9	CNS cancer (glio/astro) U-	62.9
		118-MG
Fetal Lung	34.9	CNS cancer (neuro;met) SK-	23.5
		N-AS
Lung ca. NCI-N417	11.7	CNS cancer (astro) SF-539	21.3
Lung ca. LX-1	45.1	CNS cancer (astro) SNB-75	52.9
Lung ca. NCI-H146	18.4	CNS cancer (glio) SNB-19	24.0
Lung ca. SHP-77	62.0	CNS cancer (glio) SF-295	70.2
Lung ca. A549	51.4	Brain (Amygdala) Pool	17.0
Lung ca. NCI-H526	10.4	Brain (cerebellum)	51.1
Lung ca. NCI-H23	25.5	Brain (fetal)	37.9
Lung ca. NCI-H460	24.1	Brain (Hippocampus) Pool	18.6
Lung ca. HOP-62	20.3	Cerebral Cortex Pool	21.0
Lung ca. NCI-H522	23.2	Brain (Substantia nigra)	14.5
		Pool
Liver	2.0	Brain (Thalamus) Pool	32.3
Fetal Liver	18.0	Brain (whole)	29.5
Liver ca. HepG2	10.7	Spinal Cord Pool	19.6
Kidney Pool	14.5	Adrenal Gland	15.5
Fetal Kidney	32.3	Pituitary gland Pool	6.4
Renal ca. 786-0	29.5	Salivary Gland	6.5
Renal ca. A498	14.5	Thyroid (female)	7.7
Renal ca. ACHN	17.2	Pancreatic ca. CAPAN2	19.8
Renal ca. UO-31	24.5	Pancreas Pool	12.9

[0785]

TABLE VD
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4701, Run		Ag4701, Run
Tissue Name	200924228	Tissue Name	200924228
Secondary Th1 act	63.7	HUVEC IL-1 beta	100.0
Secondary Th2 act	57.8	HUVEC IFN gamma	94.0
Secondary Tr1 act	60.3	HUVEC TNF alpha + IFN	56.3
		gamma
Secondary Th1 rest	5.0	HUVEC TNF alpha + IL4	65.1
Secondary Th2 rest	7.5	HUVEC IL-11	49.7
Secondary Tr1 rest	7.9	Lung Microvascular EC	90.8
		none
Primary Th1 act	57.4	Lung Microvascular EC	64.2
		TNF alpha + IL-1 beta
Primary Th2 act	54.7	Microvascular Dermal EC	61.6
		none
Primary Tr1 act	51.1	Microsvasular Dermal EC	51.1
		TNF alpha + IL-1 beta
Primary Th1 rest	8.7	Bronchial epithelium	52.5
		TNF alpha + IL1 beta
Primary Th2 rest	4.6	Small airway epithelium	29.7
		none
Primary Tr1 rest	11.1	Small airway epithelium	60.7
		TNF alpha + IL-1 beta
CD45RA CD4 lymphocyte	58.6	Coronery artery SMC rest	52.9
act
CD45RO CD4 lymphocyte	47.0	Coronery artery SMC	49.0
act		TNF alpha + IL-1 beta
CD8 lymphocyte act	43.5	Astrocytes rest	41.8
Secondary CD8 lymphocyte	46.0	Astrocytes TNF alpha + IL-	31.9
rest		1 beta
Secondary CD8 lymphocyte	18.9	KU-812 (Basophil) rest	48.3
act
CD4 lymphocyte none	3.5	KU-812 (Basophil)	90.8
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	11.7	CCD1106 (Keratinocytes)	84.7
CD95 CH11		none
LAK cells rest	33.7	CCD1106 (Keratinocytes)	69.7
		TNF alpha + IL-1 beta
LAK cells IL-2	29.5	Liver cirrhosis	12.9
LAK cells IL-2 + IL-12	21.6	NCI-H292 none	49.7
LAK cells IL-2 + IFN	19.5	NCI-H292 IL-4	68.3
gamma
LAK cells IL-2 + IL-18	19.3	NCI-H292 IL-9	87.7
LAK cells PMA/ionomycin	37.1	NCI-H292 IL-13	67.4
NK Cells IL-2 rest	29.9	NCI-H292 IFN gamma	59.9
Two Way MLR 3 day	20.7	HPAEC none	55.1
Two Way MLR 5 day	29.1	HPAEC TNF alpha + IL-1	95.3
		beta
Two Way MLR 7 day	21.5	Lung fibroblast none	64.2
PBMC rest	6.3	Lung fibroblast TNF alpha +	38.7
		IL-1 beta
PBMC PWM	36.1	Lung fibroblast IL-4	57.4
PBMC PHA-L	33.7	Lung fibroblast IL-9	72.7
Ramos (B cell) none	31.6	Lung fibroblast IL-13	52.1
Ramos (B cell) ionomycin	41.8	Lung fibroblast IFN gamma	71.2
B lymphocytes PWM	43.2	Dermal fibroblast CCD1070	90.8
		rest
B lymphocytes CD40L and	17.7	Dermal fibroblast CCD1070	85.3
IL-4		TNF alpha
EOL-1 dbcAMP	59.5	Dermal fibroblast CCD1070	55.5
		IL-1 beta
EOL-1 dbcAMP	45.1	Dermal fibroblast IFN	46.7
PMA/ionomycin		gamma
Dendritic cells none	27.2	Dermal fibroblast IL-4	88.9
Dendritic cells LPS	31.9	Dermal Fibroblasts rest	55.1
Dendritic cells anti-CD40	28.1	Neutrophils TNFa + LPS	10.7
Monocytes rest	23.2	Neutrophils rest	12.3
Monocytes LPS	48.0	Colon	12.2
Macrophages rest	27.5	Lung	29.9
Macrophages LPS	18.9	Thymus	24.7
HUVEC none	62.4	Kidney	37.1
HUVEC starved	88.3

[0786] CNS_neurodegeneration_v1.0 Summary: Ag4701 This panel confirms the expression of the CG107363-02 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 this gene in treatment of central nervous system disorders.

[0787] General_screening_panel_v1.4 Summary: Ag4701 Highest expression of the CG107363-02 gene is detected in breast cancer BT 549 cell line (CT=23.7). High levels of expression of this gene is also seen in cluster of cancer cell lines derived from pancreatic, gastric, colon, lung, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers. 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 pancreatic, gastric, colon, lung, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers.

[0788] Among tissues with metabolic or endocrine function, this gene is expressed at high 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.

[0789] 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, therapeutic modulation of this gene product may be useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0790] Panel 4.1D Summary: Ag4701 Highest expression of the CG107363-02 gene is detected in IL-beta treated HUVEC cells (CT=25.4). 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.

W. CG108360-01: PAX Transcription Activation Domain Interacting Protein PTIP

[0791] Expression of gene CG108360-01 was assessed using the primer-probe set Ag4355, described in Table WA. Results of the RTQ-PCR runs are shown in Tables WB, WC and WD.

TABLE WA
Probe Name Ag4355
			Start	SEQ ID
Primers	Sequences	Length	Positon	No
Forward	5′-gtgtctgcagagttgttgatga-3′	22	2518	156
Probe	TET-5′-cctcccaaactgaaacagaatgaagt-3′-TAMRA	26	2551	157
Reverse	5′-cttcaattctggctcttttgg-3′-	21	2597	158

[0792]

TABLE WB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4355, Run		Ag4355, Run
Tissue Name	224371499	Tissue Name	224371499
AD 1 Hippo	0.0	Control (Path) 3 Temporal	0.0
		Ctx
AD 2 Hippo	0.0	Control (Path) 4 Temporal	0.0
		Ctx
AD 3 Hippo	0.0	AD 1 Occipital Ctx	0.0
AD 4 Hippo	0.0	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 Hippo	0.0	AD 3 Occipital Ctx	0.0
AD 6 Hippo	0.0	AD 4 Occipital Ctx	0.0
Control 2 Hippo	0.0	AD 5 Occipital Ctx	0.0
Control 4 Hippo	55.9	AD 6 Occipital Ctx	0.0
Control (Path) 3 Hippo	58.2	Control 1 Occipital Ctx	0.0
AD 1 Temporal Ctx	0.0	Control 2 Occipital Ctx	0.0
AD 2 Temporal Ctx	0.0	Control 3 Occipital Ctx	0.0
AD 3 Temporal Ctx	0.0	Control 4 Occipital Ctx	0.0
AD 4 Temporal Ctx	0.0	Control (Path) 1 Occipital	0.0
		Ctx
AD 5 Inf Temporal Ctx	0.0	Control (Path) 2 Occipital	0.0
		Ctx
AD 5 Sup Temporal Ctx	40.9	Control (Path) 3 Occipital	0.0
		Ctx
AD 6 Inf Temporal Ctx	0.0	Control (Path) 4 Occipital	0.0
		Ctx
AD 6 Sup Temporal Ctx	100.0	Control 1 Parietal Ctx	0.0
Control 1 Temporal Ctx	0.0	Control 2 Parietal Ctx	0.0
Control 2 Temporal Ctx	0.0	Control 3 Parietal Ctx	0.0
Control 3 Temporal Ctx	0.0	Control (Path) 1 Parietal	0.0
		Ctx
Control 3 Temporal Ctx	0.0	Control (Path) 2 Parietal	0.0
		Ctx
Control (Path) 1 Temporal	0.0	Control (Path) 3 Parietal	0.0
Ctx		Ctx
Control (Path) 2 Temporal	0.0	Control (Path) 4 Parietal	0.0
Ctx		Ctx

[0793]

TABLE WC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4355, Run		Ag4355, Run
Tissue Name	222543194	Tissue Name	222543194
Adipose	9.2	Renal ca. TK-10	30.8
Melanoma* Hs688(A).T	12.7	Bladder	15.6
Melanoma* Hs688(B).T	13.2	Gastric ca. (liver met.) NCI-	2.9
		N87
Melanoma* M14	57.8	Gastric ca. KATO III	100.0
Melanoma* LOXIMVI	37.1	Colon ca. SW-948	10.5
Melanoma* SK-MEL-5	92.0	Colon ca. SW480	86.5
Squamous cell carcinoma	20.0	Colon ca.* (SW480 met)	70.2
SCC-4		SW620
Testis Pool	18.4	Colon ca. HT29	28.9
Prostate ca.* (bone met)	15.5	Colon ca. HCT-116	61.1
PC-3
Prostate Pool	9.6	Colon ca. CaCo-2	62.9
Placenta	8.3	Colon cancer tissue	36.3
Uterus Pool	5.3	Colon ca. SW1116	20.4
Ovarian ca. OVCAR-3	20.7	Colon ca. Colo-205	17.6
Ovarian ca. SK-OV-3	35.4	Colon ca. SW-48	15.1
Ovarian ca. OVCAR-4	9.6	Colon Pool	11.9
Ovarian ca. OVCAR-5	33.9	Small Intestine Pool	18.2
Ovarian ca. IGROV-1	19.1	Stomach Pool	8.0
Ovarian ca. OVCAR-8	9.9	Bone Marrow Pool	7.3
Ovary	7.0	Fetal Heart	18.0
Breast ca. MCF-7	31.0	Heart Pool	5.6
Breast ca. MDA-MB-231	61.1	Lymph Node Pool	18.0
Breast ca. BT 549	70.7	Fetal Skeletal Muscle	9.1
Breast ca. T47D	51.4	Skeletal Muscle Pool	9.7
Breast ca. MDA-N	24.0	Spleen Pool	8.9
Breast Pool	15.2	Thymus Pool	31.6
Trachea	7.4	CNS cancer (glio/astro)	65.5
		U87-MG
Lung	3.5	CNS cancer (glio/astro) U-	68.8
		118-MG
Fetal Lung	30.4	CNS cancer (neuro;met)	33.9
		SK-N-AS
Lung ca. NCI-N417	20.9	CNS cancer (astro) SF-539	22.4
Lung ca. LX-1	38.2	CNS cancer (astro) SNB-75	70.2
Lung ca. NCI-H146	18.9	CNS cancer (glio) SNB-19	17.3
Lung ca. SHP-77	34.9	CNS cancer (glio) SF-295	73.2
Lung ca. A549	49.0	Brain (Amygdala) Pool	3.0
Lung ca. NCI-H526	35.8	Brain (cerebellum)	41.2
Lung ca. NCI-H23	80.7	Brain (fetal)	12.8
Lung ca. NCI-H460	20.2	Brain (Hippocampus) Pool	2.6
Lung ca. HOP-62	8.8	Cerebral Cortex Pool	5.7
Lung ca. NCI-H522	40.1	Brain (Substantia nigra)	5.0
		Pool
Liver	0.7	Brain (Thalamus) Pool	8.2
Fetal Liver	29.9	Brain (whole)	12.0
Liver ca. HepG2	15.2	Spinal Cord Pool	4.3
Kidney Pool	21.6	Adrenal Gland	8.2
Fetal Kidney	26.4	Pituitary gland Pool	5.1
Renal ca. 786-0	27.4	Salivary Gland	5.1
Renal ca. A498	31.9	Thyroid (female)	4.0
Renal ca. ACHN	15.8	Pancreatic ca. CAPAN2	49.7
Renal ca. UO-31	31.2	Pancreas Pool	17.2

[0794]

TABLE WD
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4355, Run		Ag4355, Run
Tissue Name	186365411	Tissue Name	186365411
Secondary Th1 act	71.2	HUVEC IL-1beta	23.8
Secondary Th2 act	54.3	HUVEC IFN gamma	22.7
Secondary Tr1 act	48.0	HUVEC TNF alpha + IFN	8.2
		gamma
Secondary Th1 rest	10.5	HUVEC TNF alpha + IL4	19.9
Secondary Th2 rest	12.0	HUVEC IL-11	13.7
Secondary Tr1 rest	10.7	Lung Microvascular EC	22.7
		none
Primary Th1 act	39.2	Lung Microvascular EC	17.6
		TNF aplha + IL-1beta
Primary Th2 act	50.7	Microvascular Dermal EC	13.6
		none
Primary Tr1 act	41.5	Microsvasular Dermal EC	11.6
		TNF aplha + IL-1beta
Primary Th1 rest	9.8	Bronchial epithelium	15.9
		TNF aplha + IL1beta
Primary Th2 rest	9.0	Small airway epithelium	6.3
		none
Primary Tr1 rest	23.2	Small airway epithelium	12.5
		TNF aplha + IL-1beta
CD45RA CD4 lymphocyte	46.3	Coronery artery SMC rest	8.7
act
CD45RO CD4 lymphocyte	62.9	Coronery artery SMC	6.3
act		TNF aplha + IL-1beta
CD8 lymphocyte act	58.2	Astrocytes rest	7.9
Secondary CD8 lymphocyte	54.7	Astrocytes TNF aplha + IL-	4.7
rest		1beta
Secondary CD8 lymphocyte	26.2	KU-812 (Basophil) rest	49.3
act
CD4 lymphocyte none	10.6	KU-812 (Basophil)	44.4
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-	19.5	CCD1106 (Keratinocytes)	25.5
CD95 CH11		none
LAK cells rest	15.3	CCD1106 (Keratinocytes)	15.7
		TNF aplha + IL-1beta
LAK cells IL-2	31.4	Liver cirrhosis	4.3
LAK cells IL-2 + IL-12	25.7	NCI-H292 none	17.7
LAK cells IL-2 + IFN	19.6	NCI-H292 IL-4	34.2
gamma
LAK cells IL-2 + IL-18	39.2	NCI-H292 IL-9	37.9
LAK cells PMA/ionomycin	12.2	NCI-H292 IL-13	36.3
NK Cells IL-2 rest	56.6	NCI-H292 IFN gamma	26.8
Two Way MLR 3 day	21.3	HPAEC none	11.3
Two Way MLR 5 day	46.3	HPAEC TNF alpha + IL-1	21.2
		beta
Two Way MLR 7 day	27.5	Lung fibroblast none	19.2
PBMC rest	11.1	Lung fibroblast TNF alpha +	11.0
		IL-1beta
PBMC PWM	34.4	Lung fibroblast IL-4	13.1
PBMC PHA-L	35.1	Lung fibroblast IL-9	33.7
Ramos (B cell) none	36.9	Lung fibroblast IL-13	20.9
Ramos (B cell) ionomycin	60.3	Lung fibroblast IFN gamma	22.4
B lymphocytes PWM	51.8	Dermal fibroblast CCD1070	24.5
		rest
B lymphocytes CD40L and	32.8	Dermal fibroblast CCD1070	53.2
IL-4		TNF alpha
EOL-1 dbcAMP	100.0	Dermal fibroblast CCD1070	19.1
		IL-1beta
EOL-1 dbcAMP	47.6	Dermal fibroblast IFN	15.8
PMA/ionomycin		gamma
Dendritic cells none	13.3	Dermal fibroblast IL-4	22.4
Dendritic cells LPS	6.9	Dermal Fibroblasts rest	12.8
Dendritic cells anti-CD40	10.8	Neutrophils TNFa + LPS	1.7
Monocytes rest	15.2	Neutrophils rest	6.7
Monocytes LPS	15.2	Colon	6.2
Macrophages rest	13.3	Lung	6.7
Macrophages LPS	4.7	Thymus	94.6
HUVEC none	13.2	Kidney	15.2
HUVEC starved	22.5

[0795] General_screening_panel13v1.4 Summary: Ag4355 Highest expression of this gene is seen in a gastric cancer cell line (CT=27.8). This gene is ubiquitously expressed in this panel, with moderate expression seen in brain, colon, gastric, lung, breast, ovarian, and melanoma cancers. In addition, this gene is expressed at much higher levels in fetal lung and liver (CTs=29) when compared to expression in the adult counterpart (CTs=32-35). Thus, expression of this gene may be used to differentiate between the fetal and adult sources of these tissues. Higher levels of expression of this gene in fetal tissue and cancer cell lines suggest a role for this gene product in cell survival and proliferation. Therefore, modulation of the expression or activity of gene product may be useful in the treatment of cancer.

[0796] 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 function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0797] This gene is also expressed at moderate to low but significant levels in the CNS, including the thalamus, substantia nigra, amygdala, cerebellum 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.

[0798] Panel 4.1D Summary: Ag4355 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 eosinophils (CT=29.2). 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_panel13v1.4 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.

X. CG108762-01: MAP1 Light Chain 3 Related Protein-like protein

[0799] Expression of gene CG108762-01 was assessed using the primer-probe set Ag4371, described in Table XA. Results of the RTQ-PCR runs are shown in Tables XB, XC, XD, XE and XF.

TABLE XA
Probe Name Ag4371
			Start	SEQ ID
Primer	Sequences	Lengh	Position	No
Forward	5′-aattcatctccgagctgagg-3′	20	202	159
Probe	TET-5′-tcaacaatgtcattctgcccaccagt-3′-TAMRA	26	240	160
Reverse	5′-tggtgttcctggtagagctg-3′	20	278	161

[0800]

TABLE XB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4371, Run		Ag4371, Run
Tissue Name	224377285	Tissue Name	224377285
AD 1 Hippo	32.3	Control (Path) 3 Temporal	10.4
		Ctx
AD 2 Hippo	56.3	Control (Path) 4 Temporal	18.4
		Ctx
AD 3 Hippo	14.1	AD 1 Occipital Ctx	14.5
AD 4 Hippo	10.5	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 Hippo	44.4	AD 3 Occipital Ctx	11.5
AD 6 Hippo	69.7	AD 4 Occipital Ctx	25.3
Control 2 Hippo	52.9	AD 5 Occipital Ctx	29.3
Control 4 Hippo	24.7	AD 6 Occipital Ctx	12.7
Control (Path) 3 Hippo	11.9	Control 1 Occipital Ctx	7.5
AD 1 Temporal Ctx	18.4	Control 2 Occipital Ctx	81.8
AD 2 Temporal Ctx	46.0	Control 3 Occipital Ctx	15.0
AD 3 Temporal Ctx	10.1	Control 4 Occipital Ctx	14.6
AD 4 Temporal Ctx	13.3	Control (Path) 1 Occipital	55.5
		Ctx
AD 5 Inf Temporal Ctx	85.9	Control (Path) 2 Occipital	13.3
		Ctx
AD 5 Sup Temporal Ctx	44.4	Control (Path) 3 Occipital	8.6
		Ctx
AD 6 Inf Temporal Ctx	49.7	Control (Path) 4 Occipital	10.2
		Ctx
AD 6 Sup Temporal Ctx	63.7	Control 1 Parietal Ctx	20.3
Control 1 Temporal Ctx	13.8	Control 2 Parietal Ctx	44.8
Control 2 Temporal Ctx	51.1	Control 3 Parietal Ctx	16.8
Control 3 Temporal Ctx	16.7	Control (Path) 1 Parietal Ctx	100.0
Control 3 Temporal Ctx	11.9	Control (Path) 2 Parietal Ctx	22.1
Control (Path) 1 Temporal	57.8	Control (Path) 3 Parietal Ctx	7.8
Ctx
Control (Path) 2 Temporal	48.3	Control (Path) 4 Parietal Ctx	27.0
Ctx

[0801]

TABLE XC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4371, Run		Ag4371, Run
Tissue Name	222544262	Tissue Name	222544262
Adipose	31.6	Renal ca. TK-10	31.4
Melanoma* Hs688(A).T	58.6	Bladder	55.9
Melanoma* Hs688(B).T	49.3	Gastric ca. (liver met.) NCI-	26.2
		N87
Melanoma* M14	50.3	Gastric ca. KATO III	47.0
Melanoma* LOXIMVI	36.9	Colon ca. SW-948	22.5
Melanoma* SK-MEL-5	88.3	Colon ca. SW480	48.0
Squamous cell carcinoma	18.4	Colon ca.* (SW480 met)	64.6
SCC-4		SW620
Testis Pool	24.5	Colon ca. HT29	17.7
Prostate ca.* (bone met)	44.1	Colon ca. HCT-116	41.2
PC-3
Prostate Pool	19.1	Colon ca. CaCo-2	24.0
Placenta	34.4	Colon cancer tissue	23.5
Uterus Pool	4.7	Colon ca. SW1116	9.4
Ovarian ca. OVCAR-3	32.5	Colon ca. Colo-205	13.0
Ovarian ca. SK-OV-3	23.7	Colon ca. SW-48	18.0
Ovarian ca. OVCAR-4	27.4	Colon Pool	25.5
Ovarian ca. OVCAR-5	52.1	Small Intestine Pool	23.5
Ovarian ca. IGROV-1	41.8	Stomach Pool	11.7
Ovarian ca. OVCAR-8	27.7	Bone Marrow Pool	31.9
Ovary	29.5	Fetal Heart	31.4
Breast ca. MCF-7	55.9	Heart Pool	24.1
Breast ca. MDA-MB-231	62.4	Lymph Node Pool	25.3
Breast ca. BT 549	85.9	Fetal Skeletal Muscle	23.2
Breast ca. T47D	86.5	Skeletal Muscle Pool	21.3
Breast ca. MDA-N	36.3	Spleen Pool	18.3
Breast Pool	24.1	Thymus Pool	21.0
Trachea	33.2	CNS cancer (glio/astro) U87-	55.1
		MG
Lung	11.7	CNS cancer (glio/astro) U-	100.0
		118-MG
Fetal Lung	55.9	CNS cancer (neuro;met) SK-	37.1
		N-AS
Lung ca. NCI-N417	11.9	CNS cancer (astro) SF-539	35.4
Lung ca. LX-1	41.8	CNS cancer (astro) SNB-75	78.5
Lung ca. NCI-H146	21.0	CNS cancer (glio) SNB-19	36.3
Lung ca. SHP-77	45.4	CNS cancer (glio) SF-295	60.3
Lung ca. A549	48.3	Brain (Amygdala) Pool	33.9
Lung ca. NCI-H526	17.6	Brain (cerebellum)	47.6
Lung ca. NCI-H23	55.9	Brain (fetal)	26.4
Lung ca. NCI-H460	26.4	Brain (Hippocampus) Pool	19.9
Lung ca. HOP-62	34.6	Cerebral Cortex Pool	32.1
Lung ca. NCI-H522	41.2	Brain (Substantia nigra) Pool	31.6
Liver	7.3	Brain (Thalamus) Pool	39.8
Fetal Liver	32.8	Brain (whole)	49.7
Liver ca. HepG2	25.2	Spinal Cord Pool	32.5
Kidney Pool	42.6	Adrenal Gland	59.5
Fetal Kidney	37.1	Pituitary gland Pool	14.9
Renal ca. 786-0	43.8	Salivary Gland	33.7
Renal ca. A498	32.8	Thyroid (female)	36.9
Renal ca. ACHN	45.1	Pancreatic ca. CAPAN2	20.6
Renal ca. UO-31	56.3	Pancreas Pool	37.1

[0802]

TABLE XD
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4371, Run		Ag4371, Run
Tissue Name	186473883	Tissue Name	186473883
Secondary Th1 act	27.9	HUVEC IL-1beta	35.8
Secondary Th2 act	40.3	HUVEC IFN gamma	65.1
Secondary Tr1 act	36.3	HUVEC TNF alpha + IFN	32.3
		gamma
Secondary Th1 rest	32.5	HUVEC TNF alpha + IL4	30.4
Secondary Th2 rest	25.9	HUVEC IL-11	35.4
Secondary Tr1 rest	26.4	Lung Microvascular EC none	95.9
Primary Th1 act	21.6	Lung Microvascular EC	75.8
		TNF aplha + IL-1beta
Primary Th2 act	41.5	Microvascular Dermal EC	42.3
		none
Primary Tr1 act	31.4	Microsvasular Dermal EC	33.4
		TNF aplha + IL-1beta
Primary Th1 rest	22.4	Bronchial epithelium	40.1
		TNF aplha + IL1beta
Primary Th2 rest	15.7	Small airway epithelium none	25.9
Primary Tr1 rest	19.2	Small airway epithelium	44.4
		TNF aplha + IL-1beta
CD45RA CD4 lymphocyte	31.0	Coronery artery SMC rest	54.0
act
CD45RO CD4 lymphocyte	28.1	Coronery artery SMC	64.2
act		TNF aplha + IL-1beta
CD8 lymphocyte act	36.6	Astrocytes rest	33.9
Secondary CD8 lymphocyte	26.6	Astrocytes TNF aplha + IL-	30.4
rest		1beta
Secondary CD8 lymphocyte	13.4	KU-812 (Basophil) rest	24.0
act
CD4 lymphocyte none	16.6	(KU-812 (Basophil)	37.1
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	31.6	CCD1106 (Keratinocytes)	24.7
CH11		none
LAK cells rest	66.4	CCD1106 (Keratinocytes)	15.8
		TNF aplha + IL-1beta
LAK cells IL-2	28.9	Liver cirrhosis	15.8
LAK cells IL-2 + IL-12	18.7	NCI-H292 none	35.6
LAK cells IL-2 + IFN gamma	15.4	NCI-H292 IL-4	40.6
LAK cells IL-2 + IL-18	16.4	NCI-H292 IL-9	38.7
LAK cells PMA/ionomycin	50.7	NCI-H292 IL-13	34.4
NK Cells IL-2 rest	47.6	NCI-H292 IFN gamma	31.4
Two Way MLR 3 day	42.3	HPAEC none	32.5
Two Way MLR 5 day	31.2	HPAEC TNF alpha + IL-1	68.8
		beta
Two Way MLR 7 day	18.9	Lung fibroblast none	67.8
PBMC rest	27.2	Lung fibroblast TNF alpha +	29.9
		IL-1beta
PBMC PWM	20.4	Lung fibroblast IL-4	41.8
PBMC PHA-L	31.4	Lung fibroblast IL-9	77.9
Ramos (B cell) none	14.1	Lung fibroblast IL-13	63.3
Ramos (B cell) ionomycin	24.8	Lung fibroblast IFN gamma	71.2
B lymphocytes PWM	14.9	Dermal fibroblast CCD1070	39.8
		rest
B lymphocytes CD40L and	35.8	Dermal fibroblast CCD1070	63.7
IL-4		TNF alpha
EOL-1 dbcAMP	50.0	Dermal fibroblast CCD1070	15.0
		IL-1beta
EOL-1 dbcAMP	22.5	Dermal fibroblast IFN gamma	38.7
PMA/ionomycin
Dendritic cells none	67.4	Dermal fibroblast IL-4	84.7
Dendritic cells LPS	52.1	Dermal Fibroblasts rest	40.1
Dendritic cells anti-CD40	65.1	Neutrophils TNFa + LPS	43.8
Monocytes rest	100.0	Neutrophils rest	66.9
Monocytes LPS	70.2	Colon	15.1
Macrophages rest	52.1	Lung	32.5
Macrophages LPS	31.6	Thymus	41.2
HUVEC none	34.9	Kidney	47.6
HUVEC starved	57.0

[0803]

TABLE XE
Panel CNS_1
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4371, Run		Ag4371,
Tissue Name	190320680	Tissue Name	Run 190320680
BA4 Control	10.2	BA17 PSP	15.4
BA4 Control2	21.6	BA17 PSP2	9.0
BA4 Alzheimer's2	3.1	Sub Nigra Control	41.5
BA4 Parkinson's	38.2	Sub Nigra Control2	32.1
BA4 Parkinson's2	69.3	Sub Nigra Alzheimer's2	14.8
BA4 Huntingon's	23.2	Sub Nigra Parkinson's2	57.8
BA4 Huntington's2	4.5	Sub Nigra Huntington's	100.0
BA4 PSP	10.1	Sub Nigra Huntington's2	12.5
BA4 PSP2	12.4	Sub Nigra PSP2	9.0
BA4 Depression	14.1	Sub Nigra Depression	13.7
BA4 Depression2	8.4	Sub Nigra Depression2	0.2
BA7 Control	54.3	Glob Palladus Control	18.6
BA7 Control2	28.3	Glob Palladus Control2	9.9
BA7 Alzheimer's2	6.4	Glob Palladus Alzheimer's	13.9
BA7 Parkinson's	27.0	Glob Palladus Alzheimer's2	6.7
BA7 Parkinson's2	25.5	Glob Palladus Parkinson's	90.8
BA7 Huntington's	32.8	Glob Palladus Parkinson's2	14.2
BA7 Huntington's2	55.9	Glob Palladus PSP	9.1
BA7 PSP	12.9	Glob Palladus PSP2	7.4
BA7 PSP2	30.4	Glob Palladus Depression	6.0
BA7 Depression	6.0	Temp Pole Control	15.4
BA9 Control	15.6	Temp Pole Control2	37.4
BA9 Control2	28.9	Temp Pole Alzheimer's	6.5
BA9 Alzheimer's	4.2	Temp Pole Alzheimer's2	4.4
BA9 Alzheimer's2	13.8	Temp Pole Parkinson's	24.7
BA9 Parkinson's	18.7	Temp Pole Parkinson's2	23.7
BA9 Parkinson's2	33.7	Temp Pole Huntington's	32.1
BA9 Huntington's	53.6	Temp Pole PSP	2.8
BA9 Huntington's2	17.4	Temp Pole PSP2	2.5
BA9 PSP	13.1	Temp Pole Depression2	7.5
BA9 PSP2	3.6	Cing Gyr Control	40.6
BA9 Depression	10.7	Cing Gyr Control2	19.6
BA9 Depression2	3.1	Cing Gyr Alzheimer's	23.3
BA17 Control	32.5	Cing Gyr Alzheimer's2	10.2
BA17 Control2	24.5	Cing Gyr Parkinson's	26.6
BA17 Alzheimer's2	6.3	Cing Gyr Parkinson's2	47.3
BA17 Parkinson's	38.2	Cing Gyr Huntington's	80.7
BA17 Parkinson's2	36.9	Cing Gyr Huntington's2	25.2
BA17 Huntington's	38.7	Cing Gyr PSP	25.3
BA17 Huntington's2	15.5	Cing Gyr PSP2	8.0
BA17 Depression	15.9	Cing Gyr Depression	5.3
BA17 Depression2	16.4	Cing Gyr Depression2	12.2

[0804]

TABLE XF
Panel CNS_1.1
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4371, Run		Ag4371,
Tissue Name	190026607	Tissue Name	Run 190026607
Cing Gyr Depression2	16.3	BA17 PSP2	15.1
Cing Gyr Depression	12.9	BA17 PSP	30.6
Cing Gyr PSP2	8.8	BA17 Huntington's2	7.7
Cing Gyr PSP	30.6	BA17 Huntington's	24.0
Cing Gyr Huntington's2	25.3	BA17 Parkinson's2	35.8
Cing Gyr Huntington's	100.0	BA17 Parkinson's	36.3
Cing Gyr Parkinson's2	28.1	BA17 Alzheimer's2	3.9
Cing Gyr Parkinson's	51.4	BA17 Control2	37.9
Cing Gyr Alzheimer's2	9.2	BA17 Control	35.4
Cing Gyr Alzheimer's	48.6	BA9 Depression2	7.8
Cing Gyr Control2	31.2	BA9 Depression	8.4
Cing Gyr Control	69.3	BA9 PSP2	5.3
Temp Pole Depression2	6.6	BA9 PSP	19.2
Temp Pole PSP2	4.6	BA9 Huntington's2	21.6
Temp Pole PSP	5.3	BA9 Huntington's	73.7
Temp Pole Huntington's	34.9	BA9 Parkinson's2	56.3
Temp Pole Parkinson's2	22.8	BA9 Parkinson's	26.1
Temp Pole Parkinson's	21.9	BA9 Alzheimer's2	12.3
Temp Pole Alzheimer's2	6.5	BA9 Alzheimer's	5.6
Temp Pole Alzheimer's	5.2	BA9 Control2	63.3
Temp Pole Control2	52.9	BA9 Control	19.3
Temp Pole Control	19.3	BA7 Depression	7.7
Glob Palladus Depression	10.3	BA7 PSP2	34.4
Glob Palladus PSP2	7.4	BA7 PSP	42.9
Glob Palladus PSP	9.7	BA7 Huntington's2	21.0
Glob Palladus Parkinson's2	13.3	BA7 Huntington's	39.2
Glob Palladus Parkinson's	68.3	BA7 Parkinson's2	15.1
Glob Palladus Alzheimer's2	11.4	BA7 Parkinson's	16.7
Glob Palladus Alzheimer's	26.8	BA7 Alzheimer's2	5.4
Glob Palladus Control2	8.2	BA7 Control2	28.5
Glob Palladus Control	24.7	BA7 Control	25.9
Sub Nigra Depression2	13.7	BA4 Depression2	7.6
Sub Nigra Depression	15.7	BA4 Depression	16.0
Sub Nigra PSP2	10.4	BA4 PSP2	26.6
Sub Nigra Huntington's2	37.4	BA4 PSP	10.4
Sub Nigra Huntington's	62.4	BA4 Huntington's2	7.7
Sub Nigra Parkinson's2	52.9	BA4 Huntington's	30.8
Sub Nigra Alzheimer's2	23.2	BA4 Parkinson's2	59.5
Sub Nigra Control2	13.1	BA4 Parkinson's	62.9
Sub Nigra Control	56.6	BA4 Alzheimer's2	5.2
BA17 Depression2	17.7	BA4 Control2	48.3
BA17 Depression	14.0	BA4 Control	26.2

[0805] CNS_neurodegeneration_v1.0 Summary: Ag4371 This panel does not show differential expression of this gene in Alzheimer's disease. However, this expression profile confirms the expression of this gene at high levels in the brain. See Panel 1.4 for discussion of this gene in the central nervous system.

[0806] General_screening_panel13v1.4 Summary: Ag4371 Highest expression of this gene is seen in a brain cancer cell line (CT=25.3). This gene is widely expressed in this panel, with high levels of expression seen in brain, colon, gastric, lung, breast, ovarian, and melanoma cancer cell lines. This expression profile suggests a role for this gene product in cell survival and proliferation. Modulation of this gene product may be useful in the treatment of cancer.

[0807] 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 function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0808] This gene is also expressed at high levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. This novel protein has homology to human MAP1 Light Chain 3 Related Protein (GABA(A)-receptor-associated protein). Type-A receptors for the neurotransmitter GABA (gamma-aminobutyric acid) are ligand-gated chloride channels that mediate inhibitory neurotransmission. Each subunit of the pentameric receptor protein has ligand-binding sites in the amino-terminal extracellular domain and four membrane-spanning regions, one of which forms a wall of the ion channel. Each subunit also has a large intracellular loop that may be a target for protein kinases and be required for subcellular targeting and membrane clustering of the receptor, perhaps by anchoring the receptor to the cytoskeleton. Neurotransmitter receptors need to be positioned in high density in the cell membrane at sites postsynaptic to nerve terminals releasing that neurotransmitter. Other members of the superfamily of ligand-gated ion-channel receptors associate in postsynaptic-membrane clusters by binding to the proteins rapsyn or gephyrin. Wang et al. identified a new cellular protein, GABA(A)-receptor-associated protein (GABARAP), which can interact with the gamma2 subunit of GABA(A) receptors. GABARAP binds to GABA(A) receptors both in vitro and in vivo, and co-localizes with the punctate staining of GABA(A) receptors on cultured cortical neurons. Sequence analysis shows similarity between GABARAP and light chain-3 of microtubule-associated proteins 1A and 1B. Moreover, the N terminus of GABARAP is highly positively charged and features a putative tubulin-binding motif. The interactions among GABA(A) receptors, GABARAP and tubulin suggest a mechanism for the targeting and clustering of GABA(A) receptors. Because of the homology to the GABA(A)-receptor-associated protein and the high levels of expression in the brain, 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.

[0809] References:

[0810] Wang H, Bedford F K, Brandon N J, Moss S J, Olsen R W. GABA(A)-receptor-associated protein links GABA(A) receptors and the cytoskeleton. Nature Jan. 7, 1999; 397(6714):69-72.

[0811] Panel 4.1D Summary: Ag4371 Highest expression of this gene is seen in resting monocytes (CT=27.7). This gene is also 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.

[0812] Panel CNS—1 Summary: Ag4371 This panel confirms the expression of this gene at high levels in the brain. See Panel 1.4 for discussion of this gene in the central nervous system.

[0813] Panel CNS—1.1 Summary: Ag4371 This panel confirms the expression of this gene at high levels in the brain. See Panel 1.4 for discussion of this gene in the central nervous system.

Y. CG108829-01: Novel Intracelular Signaling Protein

[0814] Expression of gene CG108829-01 was assessed using the primer-probe set Ag4370, described in Table YA. Results of the RTQ-PCR runs are shown in Tables YB and YC.

TABLE YA
Probe Name Ag4370
			Start	SEQ ID
Primer	Sequences	Length	Position	No
Forward	5′-tggactccgaaagtggtatatg-3′	22	724	162
Probe	TET-5′-cctcgactccgtgctgatggact-3′-TAMRA	23	754	163
Reverse	5′-gcctgcatgtagagcaaatcta-3′	22	789	164

[0815]

TABLE YB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4370, Run		Ag4370, Run
Tissue Name	224376589	Tissue Name	224376589
AD 1 Hippo	38.4	Control (Path) 3 Temporal	1.4
		Ctx
AD 2 Hippo	57.4	Control (Path) 4 Temporal	4.4
		Ctx
AD 3 Hippo	9.6	AD 1 Occipital Ctx	40.3
AD 4 Hippo	4.1	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 hippo	4.7	AD 3 Occipital Ctx	1.7
AD 6 Hippo	4.8	AD 4 Occipital Ctx	9.5
Control 2 Hippo	1.4	AD 5 Occipital Ctx	6.2
Control 4 Hippo	100.0	AD 6 Occipital Ctx	2.9
Control (Path) 3 Hippo	0.0	Control 1 Occipital Ctx	1.7
AD 1 Temporal Ctx	46.0	Control 2 Occipital Ctx	0.0
AD 2 Temporal Ctx	19.8	Control 3 Occipital Ctx	8.8
AD 3 Temporal Ctx	5.1	Control 4 Occipital Ctx	27.7
AD 4 Temporal Ctx	2.4	Control (Path) 1 Occipital	11.7
		Ctx
AD 5 Inf Temporal Ctx	16.7	Control (Path) 2 Occipital	1.0
		Ctx
AD 5 SupTemporal Ctx	2.2	Control (Path) 3 Occipital	0.0
		Ctx
AD 6 Inf Temporal Ctx	18.4	Control (Path) 4 Occipital	8.0
		Ctx
AD 6 Sup Temporal Ctx	16.4	Control 1 Parietal Ctx	1.7
Control 1 Temporal Ctx	0.0	Control 2 Parietal Ctx	4.2
Control 2 Temporal Ctx	0.0	Control 3 Parietal Ctx	4.6
Control 3 Temporal Ctx	6.1	Control (Path) 1 Parietal	16.2
		Ctx
Control 4 Temporal Ctx	10.9	Control (Path) 2 Parietal	4.4
		Ctx
Control (Path) 1 Temporal	10.2	Control (Path) 3 Parietal	0.0
Ctx		Ctx
Control (Path) 2 Temporal	3.1	Control (Path) 4 Parietal	3.7
Ctx		Ctx

[0816]

TABLE YC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4370, Run		Ag4370, Run
Tissue Name	222544261	Tissue Name	222544261
Adipose	12.9	Renal ca. TK-10	0.0
Melanoma* Hs688(A).T	0.0	Bladder	5.1
Melanoma* Hs688(B).T	0.0	Gastric ca. (liver met.) NCI-	2.9
		N87
Melanoma* M14	0.0	Gastric ca. KATO III	0.0
Melanoma* LOXIMVI	0.0	Colon ca. SW-948	0.0
Melanoma* SK-MEL-5	3.0	Colon ca. SW480	0.0
Squamous cell carcinoma	6.7	Colon ca.* (SW480 met)	0.0
SCC-4		SW620
Testis Pool	99.3	Colon ca. HT29	0.0
Prostate ca.* (bone met) PC-3	2.9	Colon ca. HCT-116	2.2
Prostate Pool	100.0	Colon ca. CaCo-2	0.0
Placenta	0.0	Colon cancer tissue	5.6
Uterus Pool	4.2	Colon ca. SW1116	0.0
Ovarian ca. OVCAR-3	0.0	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	3.8	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	0.0	Colon Pool	9.6
Ovarian ca. OVCAR-5	2.6	Small Intestine Pool	13.6
Ovarian ca. IGROV-1	0.0	Stomach Pool	9.9
Ovarian ca. OVCAR-8	0.0	Bone Marrow Pool	0.0
Ovary	7.2	Fetal Heart	2.1
Breast ca. MCF-7	0.0	Heart Pool	13.6
Breast ca. MDA-MB-231	0.0	Lymph Node Pool	0.0
Breast ca. BT 549	2.4	Fetal Skeletal Muscle	0.0
Breast ca. T47D	0.0	Skeletal Muscle Pool	17.9
Breast ca. MDA-N	0.0	Spleen Pool	11.6
Breast Pool	0.0	Thymus Pool	11.2
Trachea	71.7	CNS cancer (glio/astro)	0.0
		U87-MG
Lung	2.1	CNS cancer (glio/astro) U-	0.0
		118-MG
Fetal Lung	4.8	CNS cancer (neuro;met)	2.5
		SK-N-AS
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-539	0.0
Lung ca. LX-1	0.0	CNS cancer (astro) SNB-75	7.4
Lung ca. NCI-H146	0.0	CNS cancer (glio) SNB-19	4.0
Lung ca. SHP-77	0.0	CNS cancer (glio) SF-295	0.0
Lung ca. A549	0.0	Brain (Amygdala) Pool	5.1
Lung ca. NCI-H526	0.0	Brain (cerebellum)	18.9
Lung ca. NCI-H23	43.2	Brain (fetal)	35.4
Lung ca. NCI-H460	0.0	Brain (Hippocampus) Pool	21.9
Lung ca. HOP-62	0.0	Cerebral Cortex Pool	12.3
Lung ca. NCI-H522	0.0	Brain (Substantia nigra)	31.6
		Pool
Liver	0.0	Brain (Thalamus) Pool	34.9
Fetal Liver	0.0	Brain (whole)	12.9
Liver ca. HepG2	0.0	Spinal Cord Pool	65.1
Kidney Pool	39.5	Adrenal Gland	2.6
Fetal Kidney	94.0	Pituitary gland Pool	8.7
Renal ca. 786-0	0.0	Salivary Gland	6.9
Renal ca. A498	0.0	Thyroid (female)	5.5
Renal ca. ACHN	0.0	Pancreatic ca. CAPAN2	0.0
Renal ca. UO-31	0.0	Pancreas Pool	8.0

[0817] CNS_neurodegeneration_v1.0 Summary: Ag4370 This panel confirms the presence of this gene in the brain. 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.

[0818] General_screening_panel_v1.4 Summary: Ag4370 Highest expression of this gene is seen in prostate (CT=31.2). Moderate levels of gene expression are also seen in trachea, fetal kidney, spinal cord, and testis. Low but significant levels of gene expression are seen in all regions of the CNS examined. Thus, expression of this gene could be used to differentiate between prostate and other samples on this panel and as a marker of prostate tissue.

Z. CG108861-01: Fish-like Protein

[0819] Expression of gene CG108861-01 was assessed using the primer-probe set Ag4381, described in Table ZA. Results of the RTQ-PCR runs are shown in Tables ZB, ZC and ZD.

TABLE ZA
Probe Name Ag4381
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-catctcacagtgtgacgaagtc-3′	22	405	165
Probe	TET-5′-ctcgacccgaggatgtcaaccct-3′-TAMRA	23	443	166
Reverse	5′-gaactgccatagtcctcttttg-3′	22	467	167

[0820]

TABLE ZB
CNS_neurodegeneration_panel_v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4381, Run		Ag4381, Run
Tissue Name	224502233	Tissue Name	224502233
AD 1 Hippo	29.9	Control (Path) 3 Temporal	18.4
		Ctx
AD 2 Hippo	39.5	Control (Path) 4 Temporal	39.5
		Ctx
AD 3 Hippo	12.2	AD 1 Occipital Ctx	26.1
AD 4 Hippo	18.2	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 Hippo	49.0	AD 3 Occipital Ctx	10.5
AD 6 Hippo	68.8	AD 4 Occipital Ctx	20.3
Control 2 Hippo	43.8	AD 5 Occipital Ctx	40.3
Control 4 Hippo	21.0	AD 6 Occipital Ctx	36.1
Control (Path) 3 Hippo	19.9	Control 1 Occipital Ctx	13.7
AD 1 Temporal Ctx	29.7	Control 2 Occipital Ctx	38.4
AD 2 Temporal Ctx	39.5	Control 3 Occipital Ctx	18.0
AD 3 Temporal Ctx	9.0	Control 4 Occipital Ctx	27.0
AD 4 Temporal Ctx	39.0	Control (Path) 1 Occipital	100.0
		Ctx
AD 5 Inf Temporal Ctx	66.9	Control (Path) 2 Occipital	28.1
		Ctx
AD 5 Sup Temporal Ctx	37.9	Control (Path) 3 Occipital	27.9
		Ctx
AD 6 Inf Temporal Ctx	70.2	Control (Path) 4 Occipital	31.9
		Ctx
AD 6 Sup Temporal Ctx	60.7	Control 1 Parietal Ctx	20.3
Control 1 Temporal Ctx	13.0	Control 2 Parietal Ctx	44.8
Control 2 Temporal Ctx	41.8	Control 3 Parietal Ctx	20.0
Control 3 Temporal Ctx	15.6	Control (Path) 1 Parietal Ctx	58.2
Control 3 Temporal Ctx	22.1	Control (Path) 2 Parietal Ctx	43.5
Control (Path) 1 Temporal	44.1	Control (Path) 3 Parietal Ctx	26.2
Ctx
Control (Path) 2 Temporal	45.7	Control (Path) 4 Parietal Ctx	57.8
Ctx

[0821]

TABLE ZC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4381, Run		Ag4381, Run
Tissue Name	222567264	Tissue Name	222567264
Adipose	4.2	Renal ca. TK-10	14.9
Melanoma* Hs688(A).T	19.1	Bladder	11.7
Melanoma* Hs688(B).T	24.8	Gastric ca. (liver met.) NCI-	6.0
		N87
Melanoma* M14	0.0	Gastric ca. KATO III	4.8
Melanoma* LOXIMVI	12.2	Colon ca. SW-948	8.4
Melanoma* SK-MEL-5	0.4	Colon ca. SW480	4.7
Squamous cell carcinoma	32.8	Colon ca.* (SW480 met)	6.7
SCC-4		SW620
Testis Pool	2.2	Colon ca. HT29	15.0
Prostate ca.* (bone met) PC-3	7.0	Colon ca. HCT-116	1.8
Prostate Pool	7.7	Colon ca. CaCo-2	16.2
Placenta	19.9	Colon cancer tissue	16.4
Uterus Pool	2.3	Colon ca. SW1116	3.9
Ovarian ca. OVCAR-3	5.0	Colon ca. Colo-205	25.5
Ovarian ca. SK-OV-3	8.7	Colon ca. SW-48	21.8
Ovarian ca. OVCAR-4	0.1	Colon Pool	11.1
Ovarian ca. OVCAR-5	14.6	Small Intestine Pool	7.9
Ovarian ca. IGROV-1	27.4	Stomach Pool	6.2
Ovarian ca. OVCAR-8	4.7	Bone Marrow Pool	8.0
Ovary	7.5	Fetal Heart	15.3
Breast ca. MCF-7	0.1	Heart Pool	5.9
Breast ca. MDA-MB-231	37.6	Lymph Node Pool	16.6
Breast ca. BT 549	100.0	Fetal Skeletal Muscle	11.4
Breast ca. T47D	15.7	Skeletal Muscle Pool	7.4
Breast ca. MDA-N	0.0	Spleen Pool	8.4
Breast Pool	12.1	Thymus Pool	11.3
Trachea	18.6	CNS cancer (glio/astro)	23.7
		U87-MG
Lung	2.8	CNS cancer (glio/astro) U-	18.8
		118-MG
Fetal Lung	58.2	CNS cancer (neuro; met) SK-	13.8
		N-AS
Lung ca. NCI-N417	3.4	CNS cancer (astro) SF-539	21.3
Lung ca. LX-1	24.7	CNS cancer (astro) SNB-75	91.4
Lung ca. NCI-H146	2.3	CNS cancer (glio) SNB-19	24.8
Lung ca. SHP-77	16.7	CNS cancer (glio) SF-295	18.7
Lung ca. A549	17.8	Brain (Amygdala) Pool	16.4
Lung ca. NCI-H526	8.8	Brain (cerebellum)	24.0
Lung ca. NCI-H23	3.9	Brain (fetal)	32.5
Lung ca. NCI-H460	1.0	(Brain Hippocampus) Pool	15.4
Lung ca. HOP-62	3.0	Cerebral Cortex Pool	13.8
Lung ca. NCI-H522	4.6	Brain (Substantia nigra)	15.8
		Pool
Liver	0.5	Brain (Thalamus) Pool	21.0
Fetal Liver	7.4	Brain (whole)	14.2
Liver ca. HepG2	67.8	Spinal Cord Pool	15.9
Kidney Pool	14.9	Adrenal Gland	3.0
Fetal Kidney	5.9	Pituitary gland Pool	1.7
Renal ca. 786-0	0.9	Salivary Gland	4.7
Renal ca. A498	1.7	Thyroid (female)	0.9
Renal ca. ACHN	2.7	Pancreatic ca. CAPAN2	2.6
Renal ca. UO-31	0.6	Pancreas Pool	14.2

[0822]

TABLE ZD
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4381, Run		Ag4381, Run
Tissue Name	186504880	Tissue Name	186504880
Secondary Th1 act	0.9	HUVEC IL-1beta	6.5
Secondary Th2 act	0.8	HUVEC IFN gamma	4.4
Secondary Tr1 act	1.4	HUVEC TNF alpha + IFN	2.1
		gamma
Secondary Th1 rest	2.3	HUVEC TNF alpha + IL4	4.9
Secondary Th2 rest	1.2	HUVEC IL-11	5.1
Secondary Tr1 rest	1.3	Lung Microvascular EC	16.4
		none
Primary Th1 act	0.2	Lung Microvascular EC	24.0
		TNF alpha + IL-1beta
Primary Th2 act	0.3	Microvascular Dermal EC	12.2
		none
Primary Tr1 act	0.6	Microsvasular Dermal EC	24.1
		TNF alpha + IL-1beta
Primary Th1 rest	0.5	Bronchial epithelium	46.3
		TNF alpha + IL1beta
Primary Th2 rest	1.0	Small airway epithelium	32.3
		none
Primary Tr1 rest	0.7	Small airway epithelium	49.3
		TNF alpha + IL-1beta
CD45RA CD4 lymphocyte	2.7	Coronery artery SMC rest	2.8
act
CD45RO CD4 lymphocyte	0.8	Coronery artery SMC	5.8
act		TNF alpha + IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	3.2
Secondary CD8 lymphocyte	0.9	Astrocytes TNF alpha + IL-	9.3
rest		1beta
Secondary CD8 lymphocyte	0.4	KU-812 (Basophil) rest	1.2
act
CD4 lymphocyte none	0.3	KU-812 (Basophil)	1.4
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	1.3	CCD1106 (Keratinocytes)	100.0
CH11		none
LAK cells rest	2.1	CCD1106 (Keratinocytes)	60.7
		TNF alpha + IL-1beta
LAK cells IL-2	0.3	Liver cirrhosis	5.4
LAK cells IL-2 + IL-12	0.4	NCI-H292 none	17.1
LAK cells IL-2 + IFN gamma	0.7	NCI-H292 IL-4	21.5
LAK cells IL-2 + IL-18	0.9	NCI-H292 IL-9	21.2
LAK cells PMA/ionomycin	1.0	NCI-H292 IL-13	16.7
NK Cells IL-2 rest	0.7	NCI-H292 IFN gamma	10.7
Two Way MLR 3 day	0.5	HPAEC none	9.4
Two Way MLR 5 day	1.1	HPAEC TNF alpha + IL-	21.2
		1beta
Two Way MLR 7 day	0.1	Lung fibroblast none	27.9
PBMC rest	0.3	Lung fibroblast TNF alpha +	11.0
		IL-1beta
PBMC PWM	0.6	Lung fibroblast IL-4	32.3
PBMC PHA-L	1.6	Lung fibroblast IL-9	34.4
Ramos (B cell) none	0.0	Lung fibroblast IL-13	32.5
Ramos (B cell) ionomycin	0.0	Lung fibroblast IFN gamma	23.3
B lymphocytes PWM	0.1	Dermal fibroblast CCD1070	12.3
		rest
B lymphocytes CD40L and	0.2	Dermal fibroblast CCD1070	10.7
IL-4		TNF alpha
EOL-1 dbcAMP	11.2	Dermal fibroblast CCD1070	4.7
		IL-1beta
EOL-1 dbcAMP	36.1	Dermal fibroblast IFN	5.1
PMA/ionomycin		gamma
Dendritic cells none	13.1	Dermal fibroblast IL-4	17.7
Dendritic cells LPS	4.1	Dermal Fibroblasts rest	8.0
Dendritic cells anti-CD40	17.9	Neutrophils TNFa+LPS	0.4
Monocytes rest	0.0	Neutrophils rest	1.2
Monocytes LPS	0.1	Colon	2.9
Macrophages rest	3.2	Lung	11.3
Macrophages LPS	0.1	Thymus	6.4
HUVEC none	4.9	Kidney	2.6
HUVEC starved	2.7

[0823] CNS_neurodegeneration_v1.0 Summary: Ag4381 This panel confirms the presence of this gene in the brain. Please see Panel 1.4 for discussion of this gene in the central nervous system.

[0824] General_screening_panel13v1.4 Summary: Ag4381 Highest expression of this gene is seen in a breast cancer cell line (CT=25.5). High levels of gene expression are seen in cell lines derived from brain, colon, liver, lung, breast, ovarian, and skin cancers. In addition, this gene is expressed at much higher levels in fetal lung and liver (CTs=26-29) when compared to expression in the adult counterpart (CTs=30-33). Thus, expression of this gene may be used to differentiate between the fetal and adult sources of these tissues. The high levels of expression of this gene in fetal tissue and cancer cell lines suggests a role for this gene product in cell survival and proliferation. Modulation of this gene product may be useful in the treatment of cancer.

[0825] 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 function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0826] This gene is also expressed at high to moderate levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum 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.

[0827] Panel 4.1D Summary: Ag4381 Highest expression is seen in untreated keratinocytes (CT=26.7). This gene is also expressed at moderate to low 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. This pattern is in agreement with the expression profile in General_screening_panel13v1.5 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.

AA. CG109523-01: Profilaggrin

[0828] Expression of gene CG109523-01 was assessed using the primer-probe set Ag4388, described in Table AAA. Results of the RTQ-PCR runs are shown in Tables AAB and AAC.

TABLE AAA
Probe Name Ag4388
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-tgaaggaacttctggaaaagg-3′	21	102	168
Probe	TET-5′-ttcggcaaatcctgaagaatccagat-3′-TAMRA	26	126	169
Reverse	5′-tccaagtgatccatgaagaca-3′	21	169	170

[0829]

TABLE AAB
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4388, Run		Ag4388, Run
Tissue Name	222567012	Tissue Name	222567012
Adipose	0.0	Renal ca. TK-10	0.1
Melanoma* Hs688(A).T	2.4	Bladder	0.0
Melanoma* Hs688(B).T	45.7	Gastric ca. (liver met.) NCI-	0.2
		N87
Melanoma* M14	0.0	Gastric ca. KATO III	0.0
Melanoma* LOXIMVI	2.8	Colon ca. SW-948	0.0
Melanoma* SK-MEL-5	0.0	Colon ca. SW480	0.0
Squamous cell carcinoma	0.2	Colon ca.* (SW480 met)	0.1
SCC-4		SW620
Testis Pool	0.0	Colon ca. HT29	0.1
Prostate ca.* (bone met)	0.0	Colon ca. HCT-116	0.0
PC-3
Prostate Pool	0.0	Colon ca. CaCo-2	0.0
Placenta	0.0	Colon cancer tissue	0.0
Uterus Pool	0.1	Colon ca. SW1116	0.0
Ovarian ca. OVCAR-3	100.0	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	0.0	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	0.0	Colon Pool	0.0
Ovarian ca. OVCAR-5	0.0	Small Intestine Pool	0.0
Ovarian ca. IGROV-1	0.2	Stomach Pool	0.0
Ovarian ca. OVCAR-8	1.0	Bone Marrow Pool	0.1
Ovary	0.0	Fetal Heart	0.0
Breast ca. MCF-7	0.0	Heart Pool	0.0
Breast ca. MDA-MB-231	12.6	Lymph Node Pool	0.0
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	0.2
Trachea	0.0	CNS cancer (glio/astro) U87-	0.0
		MG
Lung	0.0	CNS cancer (glio/astro) U-118-	0.0
		MG
Fetal Lung	0.1	CNS cancer (neuro; met) SK-	0.0
		N-AS
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-539	0.0
Lung ca. LX-1	0.2	CNS cancer (astro) SNB-75	0.3
Lung ca. NCI-H146	0.0	CNS cancer (glio) SNB-19	0.3
Lung ca. SHP-77	0.0	CNS cancer (glio) SF-295	0.0
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	0.0	Brain (Substantia nigra) Pool	0.0
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	0.2	Pituitary gland Pool	0.0
Renal ca. 786-0	51.4	Salivary Gland	0.0
Renal ca. A498	0.0	Thyroid (female)	0.0
Renal ca. ACHN	0.6	Pancreatic ca. CAPAN2	1.0
Renal ca. UO-31	0.0	Pancreas Pool	0.0

[0830]

TABLE AAC
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4388, Run		Ag4388, Run
Tissue Name	186502000	Tissue Name	186502000
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 + IFN	0.0
		gamma
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	0.0
Secondary Th2 rest	0.0	HUVEC IL-11	0.0
Secondary Tr1 rest	0.0	Lung Microvascular EC none	0.0
Primary Th1 act	0.0	Lung Microvascular EC	0.0
		TNF alpha + IL-1beta
Primary Th2 act	0.0	Microvascular Dermal EC	0.0
		none
Primary Tr1 act	0.0	Microsvasular Dermal EC	0.0
		TNF alpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium	0.0
		TNF alpha + IL1beta
Primary Th2 rest	0.0	Small airway epithelium none	0.8
Primary Tr1 rest	0.0	Small airway epithelium	2.9
		TNF alpha + IL-1beta
CD45RA CD4 lymphocyte	0.0	Coronery artery SMC rest	0.0
act
CD45RO CD4 lymphocyte	0.0	Coronery artery SMC	0.0
act		TNF alpha + IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	100.0
Secondary CD8 lymphocyte	0.0	Astrocytes TNF alpha + IL-	27.9
rest		1beta
Secondary CD8 lymphocyte	0.0	KU-812 (Basophil) rest	0.0
act
CD4 lymphocyte none	0.0	KU-812 (Basophil)	0.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	0.0	CCD1106 (Keratinocytes)	0.6
CH11		none
LAK cells rest	0.0	CCD1106 (Keratinocytes)	0.8
		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 gamma	0.0	NCI-H292 IL-4	0.6
LAK cells IL-2 + IL-18	0.0	NCI-H292 IL-9	0.0
LAK cells PMA/ionomycin	0.0	NCI-H292 IL-13	0.4
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-1	0.0
		beta
Two Way MLR 7 day	0.0	Lung fibroblast none	0.0
PBMC rest	0.0	Lung fibroblast TNF alpha +	0.0
		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) ionomycin	0.0	Lung fibroblast IFN gamma	0.0
B lymphocytes PWM	0.0	Dermal fibroblast CCD1070	0.0
		rest
B lymphocytes CD40L and	0.0	Dermal fibroblast CCD1070	0.0
IL-4		TNF alpha
EOL-1 dbcAMP	0.0	Dermal fibroblast CCD1070	0.0
		IL-1beta
EOL-1 dbcAMP	0.0	Dermal fibroblast IFN gamma	0.0
PMA/ionomycin
Dendritic cells none	0.0	Dermal fibroblast IL-4	0.0
Dendritic cells LPS	0.0	Dermal Fibroblasts rest	0.0
Dendritic cells anti-CD40	0.0	Neutrophils TNFa+LPS	0.0
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	2.5
HUVEC none	0.0	Kidney	0.5
HUVEC starved	0.0

[0831] General_screening_panel13v1.4 Summary: Ag4388 Highest expression of the CG109523-01 gene is detected in ovarian cancer OVCAR-3 cell line (CT=26). Moderate to high levels of expression of this gene are also seen in number of cancer cell lines including pancreatic, renal, breast and melanoma cancer cell lines. Therefore, expression of this gene may be used as diagnostic marker for detection of these cancers and therapeutic modulation of this gene product may be beneficial in the treatment of these cancers

[0832] Panel 4.1D Summary: Ag4388 Highest expression of the CG109523-01 gene is detected in resting astrocytes (CT=29.4). Moderate expression of this gene is also seen in TNFalpha+IL-1beta stimulated astrocytes (CT=31.3). Therefore, therapeutic regulation of this gene or the design of therapeutics with the encoded protein could be important in the treatment of multiple sclerosis or other inflammatory diseases of the CNS. In addition, expression of this gene may also used to distinguish astrocytes from other samples used in this panel.

AB. CG109649-01: Novel Intracellular Signaling Protein

[0833] Expression of gene CG109649-01 was assessed using the primer-probe set Ag4394, described in Table ABA. Results of the RTQ-PCR runs are shown in Tables ABB, ABC and ABD.

TABLE ABA
Probe Name Ag4394
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-actgggagctttgacaacaac-3′	21	367	171
Probe	TET-5′-ctattccgacttcgcgaagctccag-3′-TAMRA	25	408	172
Reverse	5′gatctcctccctgaacgtctt-3′	21	445	173

[0834]

TABLE ABB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4394, Run		Ag4394, Run
Tissue Name	224502243	Tissue Name	224502243
AD 1 Hippo	19.9	Control (Path) 3 Temporal	6.9
		Ctx
AD 2 Hippo	26.6	Control (Path) 4 Temporal	9.6
		Ctx
AD 3 Hippo	7.8	AD 1 Occipital Ctx	20.2
AD 4 Hippo	4.4	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 Hippo	66.0	AD 3 Occipital Ctx	4.5
AD 6 Hippo	100.0	AD 4 Occipital Ctx	18.9
Control 2 Hippo	14.4	AD 5 Occipital Ctx	26.8
Control 4 Hippo	29.1	AD 6 Occipital Ctx	18.2
Control (Path) 3 Hippo	3.5	Control 1 Occipital Ctx	13.4
AD 1 Temporal Ctx	38.4	Control 2 Occipital Ctx	30.4
AD 2 Temporal Ctx	17.2	Control 3 Occipital Ctx	1.7
AD 3 Temporal Ctx	8.8	Control 4 Occipital Ctx	4.3
AD 4 Temporal Ctx	20.6	Control (Path) 1 Occipital	31.4
		Ctx
AD 5 Inf Temporal Ctx	72.2	Control (Path) 2 Occipital	7.5
		Ctx
AD 5 Sup Temporal Ctx	60.7	Control (Path) 3 Occipital	1.8
		Ctx
AD 6 Inf Temporal Ctx	81.8	Control (Path) 4 Occipital	39.5
		Ctx
AD 6 Sup Temporal Ctx	64.2	Control 1 Parietal Ctx	4.5
Control 1 Temporal Ctx	12.6	Control 2 Parietal Ctx	38.2
Control 2 Temporal Ctx	57.8	Control 3 Parietal Ctx	11.0
Control 3 Temporal Ctx	21.6	Control (Path) 1 Parietal Ctx	15.1
Control 3 Temporal Ctx	3.6	Control (Path) 2 Parietal Ctx	9.2
Control (Path) 1 Temporal	27.5	Control (Path) 3 Parietal Ctx	0.0
Ctx
Control (Path) 2 Temporal	14.9	Control (Path) 4 Parietal Ctx	30.8
Ctx

[0835]

TABLE ABC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4394, Run		Ag4394, Run
Tissue Name	222641542	Tissue Name	222641542
Adipose	12.4	Renal ca. TK-10	0.0
Melanoma* Hs688(A).T	0.0	Bladder	39.5
Melanoma* Hs688(B).T	0.0	Gastric ca. (liver met.) NCI-	2.0
		N87
Melanoma* M14	0.0	Gastric ca. KATO III	0.3
Melanoma* LOXIMVI	0.0	Colon ca. SW-948	0.5
Melanoma* SK-MEL-5	0.0	Colon ca. SW480	3.6
Squamous cell carcinoma	0.0	Colon ca.* (SW480 met)	20.3
SCC-4		SW620
Testis Pool	3.7	Colon ca. HT29	0.0
Prostate ca.* (bone met)	0.0	Colon ca. HCT-116	0.0
PC-3
Prostate Pool	4.6	Colon ca. CaCo-2	0.0
Placenta	10.7	Colon cancer tissue	47.6
Uterus Pool	3.8	Colon ca. SW1116	1.7
Ovarian ca. OVCAR-3	0.0	Colon ca. Colo-205	0.7
Ovarian ca. SK-OV-3	0.5	Colon ca. SW-48	3.2
Ovarian ca. OVCAR-4	0.0	Colon Pool	27.2
Ovarian ca. OVCAR-5	0.6	Small Intestine Pool	6.3
Ovarian ca. IGROV-1	0.0	Stomach Pool	12.9
Ovarian ca. OVCAR-8	0.0	Bone Marrow Pool	28.3
Ovary	9.2	Fetal Heart	3.9
Breast ca. MCF-7	0.0	Heart Pool	4.4
Breast ca. MDA-MB-231	0.0	Lymph Node Pool	22.1
Breast ca. BT 549	0.0	Fetal Skeletal Muscle	4.6
Breast ca. T47D	0.8	Skeletal Muscle Pool	1.5
Breast ca. MDA-N	0.0	Spleen Pool	62.4
Breast Pool	23.5	Thymus Pool	100.0
Trachea	32.8	CNS cancer (glio/astro)	0.0
		U87-MG
Lung	3.9	CNS cancer (glio/astro) U-	0.3
		118-MG
Fetal Lung	50.7	CNS cancer (neuro; met) SK-	0.0
		N-AS
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-539	0.0
Lung ca. LX-1	4.9	CNS cancer (astro) SNB-75	0.0
Lung ca. NCI-H146	0.0	CNS cancer (glio) SNB-19	0.0
Lung ca. SHP-77	2.4	CNS cancer (glio) SF-295	0.0
Lung ca. A549	0.0	Brain (Amygdala) Pool	3.5
Lung ca. NCI-H526	0.0	Brain (cerebellum)	20.0
Lung ca. NCI-H23	0.0	Brain (fetal)	1.6
Lung ca. NCI-H460	0.0	Brain (Hippocampus) Pool	5.8
Lung ca. HOP-62	0.0	Cerebral Cortex Pool	2.4
Lung ca. NCI-H522	0.0	Brain (Substantia nigra)	4.4
		Pool
Liver	6.4	Brain (Thalamus) Pool	9.3
Fetal Liver	24.8	Brain (whole)	4.7
Liver ca. HepG2	1.1	Spinal Cord Pool	12.9
Kidney Pool	28.3	Adrenal Gland	9.9
Fetal Kidney	8.8	Pituitary gland Pool	2.0
Renal ca. 786-0	0.0	Salivary Gland	9.6
Renal ca. A498	0.0	Thyroid (female)	7.4
Renal ca. ACHN	0.5	Pancreatic ca. CAPAN2	0.0
Renal ca. UO-31	0.0	Pancreas Pool	21.9

[0836]

TABLE ABD
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4394, Run		Ag4394, Run
Tissue Name	187715315	Tissue Name	187715315
Secondary Th1 act	21.2	HUVEC IL-1beta	0.0
Secondary Th2 act	26.6	HUVEC IFN gamma	0.3
Secondary Tr1 act	21.3	HUVEC TNF alpha + IFN	0.0
		gamma
Secondary Th1 rest	29.3	HUVEC TNF alpha + IL4	0.0
Secondary Th2 rest	64.6	HUVEC IL-11	0.0
Secondary Tr1 rest	39.2	Lung Microvascular EC	0.0
		none
Primary Th1 act	9.9	Lung Microvascular EC	0.0
		TNF alpha + IL-1beta
Primary Th2 act	23.2	Microvascular Dermal EC	0.1
		none
Primary Tr1 act	27.4	Microsvasular Dermal EC	0.0
		TNF alpha + IL-1beta
Primary Th1 rest	27.2	Bronchial epithelium	0.0
		TNF alpha + IL1beta
Primary Th2 rest	16.0	Small airway epithelium	0.1
		none
Primary Tr1 rest	66.9	Small airway epithelium	0.0
		TNF alpha + IL-1beta
CD45RA CD4 lymphocyte	22.4	Coronery artery SMC rest	0.0
act
CD45RO CD4 lymphocyte	79.0	Coronery artery SMC	0.0
act		TNF alpha + IL-1beta
CD8 lymphocyte act	42.0	Astrocytes rest	0.0
Secondary CD8 lymphocyte	50.3	Astrocytes TNF alpha + IL-	0.0
rest		1beta
Secondary CD8 lymphocyte	18.3	KU-812 (Basophil) rest	8.0
act
CD4 lymphocyte none	21.5	(KU-812 (Basophil)	12.2
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	49.7	CCD1106 (Keratinocytes)	0.0
CH11		none
LAK cells rest	47.0	CCD1106 (Keratinocytes)	0.0
		TNF alpha + IL-1beta
LAK cells IL-2	57.0	Liver cirrhosis	0.3
LAK cells IL-2 + IL-12	27.9	NCI-H292 none	0.0
LAK cells IL-2 + IFN gamma	49.3	NCI-H292 IL-4	0.0
LAK cells IL-2 + IL-18	50.7	NCI-H292 IL-9	0.0
LAK cells PMA/ionomycin	23.2	NCI-H292 IL-13	0.0
NK Cells IL-2 rest	100.0	NCI-H292 IFN gamma	0.0
Two Way MLR 3 day	43.8	HPAEC none	0.0
Two Way MLR 5 day	30.6	HPAEC TNF alpha + IL-	0.0
		1beta
Two Way MLR 7 day	21.8	Lung fibroblast none	0.0
PBMC rest	21.6	Lung fibroblast TNF alpha +	0.0
		IL-1beta
PBMC PWM	28.5	Lung fibroblast IL-4	0.0
PBMC PHA-L	57.4	Lung fibroblast IL-9	0.0
Ramos (B cell) none	0.3	Lung fibroblast IL-13	0.0
Ramos (B cell) ionomycin	0.3	Lung fibroblast IFN gamma	0.0
B lymphocytes PWM	31.4	Dermal fibroblast CCD1070	0.0
		rest
B lymphocytes CD40L and	50.7	Dermal fibroblast CCD1070	42.6
IL-4		TNF alpha
EOL-1 dbcAMP	66.4	Dermal fibroblast CCD1070	0.2
		IL-1beta
EOL-1 dbcAMP	18.8	Dermal fibroblast IFN	0.2
PMA/ionomycin		gamma
Dendritic cells none	40.1	Dermal fibroblast IL-4	0.3
Dendritic cells LPS	34.4	Dermal Fibroblasts rest	0.0
Dendritic cells anti-CD40	44.1	Neutrophils TNFa+LPS	22.8
Monocytes rest	49.7	Neutrophils rest	51.1
Monocytes LPS	49.0	Colon	1.4
Macrophages rest	34.4	Lung	4.1
Macrophages LPS	34.9	Thymus	42.3
HUVEC none	0.0	Kidney	0.3
HUVEC starved	0.0

[0837] CNS_neurodegeneration_v1.0 Summary: Ag4394 This panel confirms the expression of the CG 109649-01 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. See Panel 1.4 for a discussion of this gene in treatment of central nervous system disorders.

[0838] General_screening_panel_v1.4 Summary: Ag4394 Highest expression of the CG109649-01 gene is detected in thymus (CT=3 1). Moderate levels of expression of this gene are also seen in spleen (CT=31.7). Therefore, expression of this gene can be used to distinguish between these samples and other samples used in this panel. In addition, therapeutic modulation of this gene may be useful as anti-inflammatory therapeutics for the treatment of allergies, autoimmune diseases, and inflammatory diseases.

[0839] Among tissues with metabolic or endocrine function, this gene is expressed at moderate to low levels in pancreas, adipose, adrenal gland, thyroid, 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.

[0840] This gene is expressed at much higher levels in fetal (CT=32) compared to adult lung (CT=35.7). This observation suggests that expression of this gene can be used to distinguish fetal from adult lung. In addition, the relative overexpression of this gene in fetal skeletal muscle suggests that the protein product may enhance lung 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 lung related diseases.

[0841] In addition, this gene is expressed at low levels in some regions of the central nervous system examined, including thalamus, cerebellum, and spinal cord. Therefore, therapeutic modulation of this gene product may be useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0842] Low levels of expression of this gene are also seen in a colon cancer sample and also in a colon cancer cell line. Therefore, expression of this gene may be used as marker to detect colon cancer and also therapeutic modulation of this gene product may be beneficial in the treatment of colon cancer.

[0843] Panel 4.1D Summary: Ag4394 Highest expression of the CG109649-0l gene is detected in IL2 treated NK Cells (CT=29). This gene is expressed by T lymphocytes prepared under a number of conditions at moderate levels and is expressed at higher levels in treated and untreated dendritic cells, monocytes, and macrophages, basophils, TNF alpha activated dermal fibroblasts, neutrophils, thymus and lung. Dendritic cells and macrophages are powerful antigen-presenting cells (APC) whose function is pivotal in the initiation and maintenance of normal immune responses. Autoimmunity and inflammation may also be reduced by suppression of this function. Therefore, small molecule drugs that antagonzie the function of this gene product may reduce or eliminate the symptoms in patients with several types of autoimmune and inflammatory diseases, such as lupus erythematosus, Crohn's disease, ulcerative colitis, multiple sclerosis, chronic obstructive pulmonary disease, asthma, emphysema, rheumatoid arthritis, or psoriasis.

AC. CG110063-01 and CG110063-02: Vp3 Domain Containing Protein

[0844] Expression of gene CG110063-01 and variant CG110063-02 was assessed using the primer-probe set Ag4407, described in Table ACA. Results of the RTQ-PCR runs are shown in Tables ACB, ACC and ACD. Please note that CG110063-02 represents a full-length physcial clone, verifying the CG110063-01 gene prediction.

TABLE AGA
Probe Name Ag4407
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-cctatacctttcacctgaacca-3′	22	577	174
Probe	TET-5′-ctccactacgagtattcactgcccgg-3′-TAMRA	26	625	175
Reverse	5′-gttgacctagcaaccatgagat-3′	22	651	176

[0845]

TABLE ACB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4407, Run		Ag4407, Run
Tissue Name	224505298	Tissue Name	224505298
AD 1 Hippo	12.5	Control (Path) 3 Temporal	1.5
		Ctx
AD 2 Hippo	25.7	Control (Path) 4 Temporal	28.3
		Ctx
AD 3 Hippo	4.6	AD 1 Occipital Ctx	6.7
AD 4 Hippo	6.6	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 hippo	61.1	AD 3 Occipital Ctx	0.9
AD 6 Hippo	54.0	AD 4 Occipital Ctx	29.5
Control 2 Hippo	23.0	AD 5 Occipital Ctx	12.5
Control 4 Hippo	2.6	AD 6 Occipital Ctx	50.3
Control (Path) 3 Hippo	7.2	Control 1 Occipital Ctx	0.0
AD 1 Temporal Ctx	13.3	Control 2 Occipital Ctx	100.0
AD 2 Temporal Ctx	44.1	Control 3 Occipital Ctx	16.2
AD 3 Temporal Ctx	4.1	Control 4 Occipital Ctx	6.8
AD 4 Temporal Ctx	16.2	Control (Path) 1 Occipital	56.3
		Ctx
AD 5 Inf Temporal Ctx	73.7	Control (Path) 2 Occipital	8.1
		Ctx
AD 5 Sup Temporal Ctx	36.9	Control (Path) 3 Occipital	2.8
		Ctx
AD 6 Inf Temporal Ctx	28.1	Control (Path) 4 Occipital	14.5
		Ctx
AD 6 Sup Temporal Ctx	58.2	Control 1 Parietal Ctx	4.7
Control 1 Temporal Ctx	10.7	Control 2 Parietal Ctx	37.4
Control 2 Temporal Ctx	37.4	Control 3 Parietal Ctx	28.9
Control 3 Temporal Ctx	15.1	Control (Path) 1 Parietal	72.2
		Ctx
Control 4 Temporal Ctx	14.7	Control (Path) 2 Parietal	20.3
		Ctx
Control (Path) 1 Temporal	74.7	Control (Path) 3 Parietal	4.7
Ctx		Ctx
Control (Path) 2 Temporal	30.6	Control (Path) 4 Parietal	54.3
Ctx		Ctx

[0846]

TABLE ACC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4407, Run		Ag4407, Run
Tissue Name	222643602	Tissue Name	222643602
Adipose	0.8	Renal ca. TK-10	15.9
Melanoma* Hs688(A).T	6.9	Bladder	6.5
Melanoma* Hs688(B).T	5.3	Gastric ca. (liver met.) NCI-	40.9
		N87
Melanoma* M14	21.2	Gastric ca. KATO III	41.8
Melanoma* LOXIMVI	6.9	Colon ca. SW-948	6.2
Melanoma* SK-MEL-5	21.8	Colon ca. SW480	28.7
Squamous cell carcinoma	100.0	Colon ca.* (SW480 met)	22.4
SCC-4		SW620
Testis Pool	4.3	Colon ca. HT29	11.2
Prostate ca.* (bone met) PC-3	28.7	Colon ca. HCT-116	47.0
Prostate Pool	3.2	Colon ca. CaCo-2	28.9
Placenta	3.0	Colon cancer tissue	8.2
Uterus Pool	1.2	Colon ca. SW1116	3.8
Ovarian ca. OVCAR-3	27.4	Colon ca. Colo-205	14.3
Ovarian ca. SK-OV-3	15.7	Colon ca. SW-48	10.2
Ovarian ca. OVCAR-4	8.2	Colon Pool	2.7
Ovarian ca. OVCAR-5	27.7	Small Intestine Pool	3.2
Ovarian ca. IGROV-1	7.9	Stomach Pool	2.2
Ovarian ca. OVCAR-8	5.9	Bone Marrow Pool	3.4
Ovary	3.0	Fetal Heart	3.1
Breast ca. MCF-7	15.5	Heart Pool	2.3
Breast ca. MDA-MB-231	15.4	Lymph Node Pool	3.5
Breast ca. BT 549	21.6	Fetal Skeletal Muscle	1.8
Breast ca. T47D	32.5	Skeletal Muscle Pool	1.9
Breast ca. MDA-N	6.8	Spleen Pool	2.0
Breast Pool	3.7	Thymus Pool	4.5
Trachea	12.5	CNS cancer (glio/astro)	13.2
		U87-MG
Lung	1.3	CNS cancer (glio/astro) U-	25.7
		118-MG
Fetal Lung	4.9	CNS cancer (neuro; met)	41.2
		SK-N-AS
Lung ca. NCI-N417	3.8	CNS cancer (astro) SF-539	8.0
Lung ca. LX-1	38.7	CNS cancer (astro) SNB-75	31.4
Lung ca. NCI-H146	7.6	CNS cancer (glio) SNB-19	6.6
Lung ca. SHP-77	23.7	CNS cancer (glio) SF-295	31.2
Lung ca. A549	12.5	Brain (Amygdala) Pool	5.8
Lung ca. NCI-H526	3.7	Brain (cerebellum)	25.2
Lung ca. NCI-H23	20.2	Brain (fetal)	3.8
Lung ca. NCI-H460	17.1	Brain (Hippocampus) Pool	4.1
Lung ca. HOP-62	10.7	Cerebral Cortex Pool	7.4
Lung ca. NCI-H522	21.5	Brain (Substantia nigra)	5.5
		Pool
Liver	1.3	Brain (Thalamus) Pool	6.6
Fetal Liver	6.5	Brain (whole)	5.1
Liver ca. HepG2	0.1	Spinal Cord Pool	3.9
Kidney Pool	4.2	Adrenal Gland	5.6
Fetal Kidney	4.7	Pituitary gland Pool	2.5
Renal ca. 786-0	17.0	Salivary Gland	2.5
Renal ca. A498	3.9	Thyroid (female)	5.6
Renal ca. ACHN	13.0	Pancreatic ca. CAPAN2	15.9
Renal ca. UO-31	8.8	Pancreas Pool	3.7

[0847]

TABLE ACD
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4407, Run		Ag4407, Run
Tissue Name	187791587	Tissue Name	187791587
Secondary Th1 act	6.3	HUVEC IL-1beta	2.5
Secondary Th2 act	8.1	HUVEC IFN gamma	1.9
Secondary Tr1 act	7.9	HUVEC TNF alpha + IFN	0.9
		gamma
Secondary Th1 rest	1.5	HUVEC TNF alpha + IL4	2.9
Secondary Th2 rest	3.3	HUVEC IL-11	2.1
Secondary Tr1 rest	1.5	Lung Microvascular EC	5.7
		none
Primary Th1 act	2.8	Lung Microvascular EC	2.9
		TNF alpha + IL-1beta
Primary Th2 act	4.1	Microvascular Dermal EC	2.9
		none
Primary Tr1 act	4.3	Microsvasular Dermal EC	1.4
		TNF alpha + IL-1beta
Primary Th1 rest	1.8	Bronchial epithelium	27.9
		TNF alpha + IL1beta
Primary Th2 rest	1.4	Small airway epithelium	26.6
		none
Primary Tr1 rest	3.7	Small airway epithelium	92.0
		TNF alpha + IL-1beta
CD45RA CD4 lymphocyte	5.1	Coronery artery SMC rest	1.8
act
CD45RO CD4 lymphocyte	5.7	Coronery artery SMC	1.6
act		TNF alpha + IL-1beta
CD8 lymphocyte act	5.3	Astrocytes rest	1.1
Secondary CD8 lymphocyte	3.7	Astrocytes TNF alpha + IL-	1.5
rest		1beta
Secondary CD8 lymphocyte	3.2	KU-812 (Basophil) rest	4.4
act
CD4 lymphocyte none	1.3	KU-812 (Basophil)	10.4
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	2.7	CCD1106 (Keratinocytes)	16.5
CH11		none
LAK cells rest	2.0	CCD1106 (Keratinocytes)	40.9
		TNF alpha + IL-1beta
LAK cells IL-2	4.8	Liver cirrhosis	0.6
LAK cells IL-2 + IL-12	2.8	NCI-H292 none	51.1
LAK cells IL-2 + IFN gamma	2.4	NCI-H292 IL-4	91.4
LAK cells IL-2 + IL-18	1.4	NCI-H292 IL-9	66.4
LAK cells PMA/ionomycin	1.0	NCI-H292 IL-13	100.0
NK Cells IL-2 rest	4.9	NCI-H292 IFN gamma	55.9
Two Way MLR 3 day	4.8	HPAEC none	1.4
Two Way MLR 5 day	3.2	HPAEC TNF alpha + IL-1	2.3
		beta
Two Way MLR 7 day	3.3	Lung fibroblast none	1.9
PBMC rest	0.1	Lung fibroblast TNF	1.9
		alpha + IL-1beta
PBMC PWM	3.8	Lung fibroblast IL-4	2.2
PBMC PHA-L	5.4	Lung fibroblast IL-9	5.9
Ramos (B cell) none	6.6	Lung fibroblast IL-13	2.6
Ramos (B cell) ionomycin	9.2	Lung fibroblast IFN gamma	2.7
B lymphocytes PWM	3.2	Dermal fibroblast CCD1070	4.0
		rest
B lymphocytes CD40L and	4.1	Dermal fibroblast CCD1070	6.1
IL-4		TNF alpha
EOL-1 dbcAMP	5.7	Dermal fibroblast CCD1070	3.5
		IL-1beta
EOL-1 dbcAMP	3.1	Dermal fibroblast IFN	0.8
PMA/ionomycin		gamma
Dendritic cells none	1.9	Dermal fibroblast IL-4	1.6
Dendritic cells LPS	1.6	Dermal Fibroblasts rest	1.3
Dendritic cells anti-CD40	2.0	Neutrophils TNF a + LPS	1.7
Monocytes rest	0.5	Neutrophils rest	1.6
Monocytes LPS	1.8	Colon	0.9
Macrophages rest	2.3	Lung	1.1
Macrophages LPS	0.8	Thymus	1.7
HUVEC none	1.5	Kidney	3.2
HUVEC starved	3.6

[0848] CNS_neurodegeneration_v1.0 Summary: Ag4407 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. See Panel 1.4 for discussion of this gene in the central nervous system.

[0849] General_screening_panel13v1.4 Summary: Ag4407 Highest expression of this gene is seen in a skin cancer cell line (CT=26.4). This gene is widely expressed in this panel, with moderate expression seen in brain, colon, gastric, lung, breast, ovarian, and melanoma cancers. This expression profile suggests a role for this gene product in cell survival and proliferation. Modulation of this gene product may be useful in the treatment of cancer.

[0850] Among tissues with metabolic function, this gene is expressed at moderate to 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 function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0851] This gene is also expressed at moderate levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum 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.

[0852] Panel 4.1D Summary: Ag4407 This transcript is widely expressed in this panel, with highest expression in NCI-H292 cells stimulated by IL-13 (CT=27.4). The gene is also 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. Mucus overproduction is an important feature of bronchial asthma and chronic obstructive pulmonary disease samples. The transcript is also expressed in small airway epithelium treated with IL-1 beta and TNF-alpha, and at moderate levels in activated bronchial epithelium and untreated small airway epithelium. 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.

AD. CG110151-01: PX19 Like Protein

[0853] Expression of gene CG110151-01 was assessed using the primer-probe set Ag4404, described in Table ADA. Results of the RTQ-PCR runs are shown in Tables ADB and ADC.

TABLE ADA
Probe Name Ag4404
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′tgtttcctgccaatgttgat-3′	20	224	177
Probe	TET-5′-cctggaggactctattgtggacccac-3′-TAMRA	26	258	178
Reverse	5′-gtgaaggtggtcatggtctg-3′	20	289	179

[0854]

TABLE ADB
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4404, Run		Ag4404, Run
Tissue Name	222643401	Tissue Name	222643401
Adipose	0.0	Renal ca. TK-10	2.0
Melanoma* Hs688(A).T	0.9	Bladder	0.4
Melanoma* Hs688(B).T	0.2	Gastric ca. (liver met.) NCI-	1.0
		N87
Melanoma* M14	3.7	Gastric ca. KATO III	9.1
Melanoma* LOXIMVI	3.2	Colon ca. SW-948	1.0
Melanoma* SK-MEL-5	3.2	Colon ca. SW480	4.5
Squamous cell carcinoma	1.9	Colon ca.* (SW480 met)	2.7
SCC-4		SW620
Testis Pool	1.6	Colon ca. HT29	1.8
Prostate ca.* (bone met)	4.2	Colon ca. HCT-116	3.6
PC-3
Prostate Pool	1.0	Colon ca. CaCo-2	5.2
Placenta	0.6	Colon cancer tissue	0.0
Uterus Pool	0.0	Colon ca. SW1116	0.5
Ovarian ca. OVCAR-3	1.5	Colon ca. Colo-205	0.8
Ovarian ca. SK-OV-3	1.4	Colon ca. SW-48	0.9
Ovarian ca. OVCAR-4	3.9	Colon Pool	1.3
Ovarian ca. OVCAR-5	4.8	Small Intestine Pool	0.5
Ovarian ca. IGROV-1	1.0	Stomach Pool	1.0
Ovarian ca. OVCAR-8	1.4	Bone Marrow Pool	0.0
Ovary	0.2	Fetal Heart	0.0
Breast ca. MCF-7	2.0	Heart Pool	1.6
Breast ca. MDA-MB-231	2.2	Lymph Node Pool	1.2
Breast ca. BT 549	5.3	Fetal Skeletal Muscle	0.1
Breast ca. T47D	100.0	Skeletal Muscle Pool	2.0
Breast ca. MDA-N	0.9	Spleen Pool	0.0
Breast Pool	0.8	Thymus Pool	0.0
Trachea	14.0	CNS cancer (glio/astro) U87-	1.8
		MG
Lung	1.7	CNS cancer (glio/astro) U-118-	2.2
		MG
Fetal Lung	0.0	CNS cancer (neuro; met) SK-	2.8
		N-AS
Lung ca. NCI-N417	0.4	CNS cancer (astro) SF-539	0.4
Lung ca. LX-1	3.9	CNS cancer (astro) SNB-75	4.5
Lung ca. NCI-H146	0.5	CNS cancer (glio) SNB-19	0.8
Lung ca. SHP-77	2.5	CNS cancer (glio) SF-295	1.3
Lung ca. A549	2.4	Brain (Amygdala) Pool	0.7
Lung ca. NCI-H526	0.0	Brain (cerebellum)	1.0
Lung ca. NCI-H23	2.2	Brain (fetal)	0.9
Lung ca. NCI-H460	1.2	Brain (Hippocampus) Pool	0.8
Lung ca. HOP-62	2.5	Cerebral Cortex Pool	0.0
Lung ca. NCI-H522	2.0	Brain (Substantia nigra) Pool	1.0
Liver	0.8	Brain (Thalamus) Pool	1.0
Fetal Liver	0.1	Brain (whole)	0.4
Liver ca. HepG2	4.7	Spinal Cord Pool	1.9
Kidney Pool	0.1	Adrenal Gland	1.1
Fetal Kidney	1.5	Pituitary gland Pool	0.0
Renal ca. 786-0	2.1	Salivary Gland	0.2
Renal ca. A498	3.5	Thyroid (female)	0.2
Renal ca. ACHN	1.2	Pancreatic ca. CAPAN2	1.5
Renal ca. UO-31	0.4	Pancreas Pool	1.6

[0855]

TABLE ADC
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4404, Run		Ag4404, Run
Tissue Name	190279047	Tissue Name	190279047
Secondary Th1 act	0.9	HUVEC IL-1beta	0.8
Secondary Th2 act	1.1	HUVEC IFN gamma	0.4
Secondary Tr1 act	3.1	HUVEC TNF alpha + IFN	0.8
		gamma
Secondary Th1 rest	0.1	HUVEC TNF alpha + IL4	1.9
Secondary Th2 rest	0.6	HUVEC IL-11	0.9
Secondary Tr1 rest	0.2	Lung Microvascular EC none	1.3
Primary Th1 act	0.3	Lung Microvascular EC	3.1
		TNF alpha + IL-1beta
Primary Th2 act	0.2	Microvascular Dermal EC	0.9
		none
Primary Tr1 act	2.0	Microsvasular Dermal EC	2.5
		TNF alpha + IL-1beta
Primary Th1 rest	0.5	Bronchial epithelium	1.2
		TNF alpha + IL1beta
Primary Th2 rest	0.6	Small airway epithelium none	0.7
Primary Tr1 rest	0.1	Small airway epithelium	1.0
		TNF alpha + IL-1beta
CD45RA CD4 lymphocyte	0.1	Coronery artery SMC rest	0.5
act
CD45RO CD4 lymphocyte	0.1	Coronery artery SMC	0.5
act		TNF alpha + IL-1beta
CD8 lymphocyte act	0.4	Astrocytes rest	1.2
Secondary CD8 lymphocyte	2.0	Astrocytes TNF alpha + IL-	0.3
rest		1beta
Secondary CD8 lymphocyte	0.4	KU-812 (Basophil) rest	2.6
act
CD4 lymphocyte none	0.2	KU-812 (Basophil)	1.5
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	0.2	CCD1106 (Keratinocytes)	2.2
CH11		none
LAK cells rest	0.4	CCD1106 (Keratinocytes)	3.7
		TNF alpha + IL-1beta
LAK cells IL-2	0.5	Liver cirrhosis	0.1
LAK cells IL-2 + IL-12	0.8	NCI-H292 none	0.3
LAK cells IL-2 + IFN gamma	0.2	NCI-H292 IL-4	1.2
LAK cells IL-2 + IL-18	0.3	NCI-H292 IL-9	1.4
LAK cells PMA/ionomycin	0.0	NCI-H292 IL-13	0.2
NK Cells IL-2 rest	1.3	NCI-H292 IFN gamma	1.8
Two Way MLR 3 day	2.2	HPAEC none	0.7
Two Way MLR 5 day	2.8	HPAEC TNF alpha + IL-1	0.0
		beta
Two Way MLR 7 day	0.7	Lung fibroblast none	0.0
PBMC rest	0.2	Lung fibroblast TNF alpha +	0.0
		IL-1beta
PBMC PWM	1.0	Lung fibroblast IL-4	0.4
PBMC PHA-L	2.5	Lung fibroblast IL-9	2.1
Ramos (B cell) none	0.7	Lung fibroblast IL-13	0.4
Ramos (B cell) ionomycin	3.4	Lung fibroblast IFN gamma	0.7
B lymphocytes PWM	1.7	Dermal fibroblast CCD1070	0.4
		rest
B lymphocytes CD40L and	0.4	Dermal fibroblast CCD1070	0.6
IL-4		TNF alpha
EOL-1 dbcAMP	1.9	Dermal fibroblast CCD1070	0.0
		IL-1beta
EOL-1 dbcAMP	0.8	Dermal fibroblast IFN gamma	0.3
PMA/ionomycin
Dendritic cells none	0.7	Dermal fibroblast IL-4	1.3
Dendritic cells LPS	1.7	Dermal Fibroblasts rest	0.2
Dendritic cells anti-CD40	1.3	Neutrophils TNF a + LPS	0.4
Monocytes rest	2.2	Neutrophils rest	2.5
Monocytes LPS	1.3	Colon	0.0
Macrophages rest	0.9	Lung	2.2
Macrophages LPS	1.0	Thymus	15.0
HUVEC none	1.6	Kidney	100.0
HUVEC starved	1.5

[0856] General_screening_panel13v1.4 Summary: Ag4404 Highest expression of this gene is seen in a breast cancer cell line (CT=29.2).). 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 breast cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of breast cancer.

[0857] Panel 4.1D Summary: Ag4404 Highest expression of this gene is seen in kidney (CT=28.5). Thus, expression of this gene could be used to differentiate the kidney derived sample from other samples on this panel and as a marker of kidney tissue. In addition, therapeutic targeting of the expression or function of this gene may modulate kidney function and be important in the treatment of inflammatory or autoimmune diseases that affect the kidney, including lupus and glomerulonephritis.

AE. CG110340-01: Polyubiquitin-like Protein

[0858] Expression of gene CG110340-01 was assessed using the primer-probe set Ag4445, described in Table AEA. Results of the RTQ-PCR runs are shown in Tables AEB, AEC and AED.

TABLE AEA
Probe Name Ag4445
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-tgcagatcttcgtgaagacc-3′	20	8	180
Probe	TET-5′-actggcaagaccatcacccttgaagt-3′-TAMRA	26	31	181
Reverse	5′-ccttcacattttcgatggtg-3′	20	69	182

[0859]

TABLE AEB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4445, Run		Ag4445, Run
Tissue Name	224535012	Tissue Name	224535012
AD 1 Hippo	16.7	Control (Path) 3 Temporal	2.4
		Ctx
AD 2 Hippo	31.9	Control (Path) 4 Temporal	34.4
		Ctx
AD 3 Hippo	5.9	AD 1 Occipital Ctx	18.0
AD 4 Hippo	8.8	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 hippo	100.0	AD 3 Occipital Ctx	6.3
AD 6 Hippo	42.9	AD 4 Occipital Ctx	19.8
Control 2 Hippo	40.6	AD 5 Occipital Ctx	19.2
Control 4 Hippo	0.0	AD 6 Occipital Ctx	40.1
Control (Path) 3 Hippo	4.1	Control 1 Occipital Ctx	1.5
AD 1 Temporal Ctx	12.9	Control 2 Occipital Ctx	54.7
AD 2 Temporal Ctx	27.0	Control 3 Occipital Ctx	17.4
AD 3 Temporal Ctx	6.0	Control 4 Occipital Ctx	2.6
AD 4 Temporal Ctx	25.0	Control (Path) 1 Occipital	80.1
		Ctx
AD 5 Inf Temporal Ctx	87.7	Control (Path) 2 Occipital	11.7
		Ctx
AD 5 SupTemporal Ctx	37.6	Control (Path) 3 Occipital	1.7
		Ctx
AD 6 Inf Temporal Ctx	46.7	Control (Path) 4 Occipital	15.1
		Ctx
AD 6 Sup Temporal Ctx	42.3	Control 1 Parietal Ctx	2.9
Control 1 Temporal Ctx	3.2	Control 2 Parietal Ctx	46.7
Control 2 Temporal Ctx	41.5	Control 3 Parietal Ctx	18.0
Control 3 Temporal Ctx	18.8	Control (Path) 1 Parietal	66.0
		Ctx
Control 4 Temporal Ctx	8.9	Control (Path) 2 Parietal	15.4
		Ctx
Control (Path) 1 Temporal	66.0	Control (Path) 3 Parietal	2.5
Ctx		Ctx
Control (Path) 2 Temporal	50.3	Control (Path) 4 Parietal	44.8
Ctx		Ctx

[0860]

TABLE AEC
General_screening_panel v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4445, Run		Ag4445, Run
Tissue Name	222693963	Tissue Name	222693963
Adipose	7.2	Renal ca. TK-10	5.5
Melanoma* Hs688(A).T	12.9	Bladder	13.2
Melanoma* Hs688(B).T	15.0	Gastric ca. (liver met.) NCI-	16.8
		N87
Melanoma* M14	24.7	Gastric ca. KATO III	42.0
Melanoma* LOXIMVI	25.0	Colon ca. SW-948	8.7
Melanoma* SK-MEL-5	100.0	Colon ca. SW480	73.7
Squamous cell carcinoma	16.4	Colon ca.* (SW480 met)	29.3
SCC-4		SW620
Testis Pool	15.8	Colon ca. HT29	9.2
Prostate ca.* (bone met) PC-3	17.7	Colon ca. HCT-116	48.3
Prostate Pool	5.1	Colon ca. CaCo-2	29.7
Placenta	5.2	Colon cancer tissue	10.0
Uterus Pool	2.5	Colon ca. SW1116	8.5
Ovarian ca. OVCAR-3	20.7	Colon ca. Colo-205	8.4
Ovarian ca. SK-OV-3	20.3	Colon ca. SW-48	8.1
Ovarian ca. OVCAR-4	12.5	Colon Pool	6.3
Ovarian ca. OVCAR-5	29.9	Small Intestine Pool	4.5
Ovarian ca. IGROV-1	24.0	Stomach Pool	3.9
Ovarian ca. OVCAR-8	6.4	Bone Marrow Pool	2.5
Ovary	6.0	Fetal Heart	12.4
Breast ca. MCF-7	25.7	Heart Pool	6.0
Breast ca. MDA-MB-231	32.3	Lymph Node Pool	6.7
Breast ca. BT 549	56.6	Fetal Skeletal Muscle	5.7
Breast ca. T47D	62.4	Skeletal Muscle Pool	20.3
Breast ca. MDA-N	7.7	Spleen Pool	7.5
Breast Pool	5.3	Thymus Pool	6.7
Trachea	8.1	CNS cancer (glio/astro)	27.9
		U87-MG
Lung	1.7	CNS cancer (glio/astro) U-	41.2
		118-MG
Fetal Lung	15.2	CNS cancer (neuro;met)	14.3
		SK-N-AS
Lung ca. NCI-N417	11.9	CNS cancer (astro) SF-539	22.1
Lung ca. LX-1	20.3	CNS cancer (astro) SNB-75	35.1
Lung ca. NCI-H146	8.4	CNS cancer (glio) SNB-19	21.5
Lung ca. SHP-77	36.6	CNS cancer (glio) SF-295	35.6
Lung ca. A549	32.3	Brain (Amygdala) Pool	12.6
Lung ca. NCI-H526	13.5	Brain (cerebellum)	9.3
Lung ca. NCI-H23	39.8	Brain (fetal)	10.9
Lung ca. NCI-H460	12.9	Brain (Hippocampus) Pool	13.0
Lung ca. HOP-62	22.1	Cerebral Cortex Pool	17.6
Lung ca. NCI-H522	15.4	Brain (Substantia nigra)	16.4
		Pool
Liver	5.6	Brain (Thalamus) Pool	20.6
Fetal Liver	23.3	Brain (whole)	9.9
Liver ca. HepG2	11.3	Spinal Cord Pool	15.1
Kidney Pool	6.3	Adrenal Gland	16.8
Fetal Kidney	12.7	Pituitary gland Pool	6.4
Renal ca. 786-0	20.7	Salivary Gland	5.8
Renal ca. A498	11.0	Thyroid (female)	11.9
Renal ca. ACHN	18.7	Pancreatic ca. CAPAN2	15.1
Renal ca. UO-31	20.6	Pancreas Pool	7.8

[0861]

TABLE AED
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag4445, Run		Ag4445, Run
Tissue Name	190826403	Tissue Name	190826403
Secondary Th1 act	68.3	HUVEC IL-1beta	66.4
Secondary Th2 act	62.4	HUVEC IFN gamma	38.2
Secondary Tr1 act	71.2	HUVEC TNF alpha + IFN	62.9
		gamma
Secondary Th1 rest	30.1	HUVEC TNF alpha + IL4	54.0
Secondary Th2 rest	29.7	HUVEC IL-11	54.3
Secondary Tr1 rest	27.4	Lung Microvascular EC	60.3
		none
Primary Th1 act	49.7	Lung Microvascular EC	64.6
		TNF alpha + IL-1beta
Primary Th2 act	43.2	Microvascular Dermal EC	37.6
		none
Primary Tr1 act	80.1	Microsvasular Dermal EC	40.3
		TNF alpha + IL-1beta
Primary Th1 rest	30.8	Bronchial epithelium	43.8
		TNF alpha + IL1beta
Primary Th2 rest	36.3	Small airway epithelium	35.6
		none
Primary Tr1 rest	46.0	Small airway epithelium	38.4
		TNF alpha + IL-1beta
CD45RA CD4 lymphocyte	49.3	Coronery artery SMC rest	58.6
act
CD45RO CD4 lymphocyte	63.3	Coronery artery SMC	40.1
act		TNF alpha + IL-1beta
CD8 lymphocyte act	64.6	Astrocytes rest	38.2
Secondary CD8 lymphocyte	51.8	Astrocytes TNF alpha + IL-	49.7
rest		1beta
Secondary CD8 lymphocyte	33.7	KU-812 (Basophil) rest	67.4
act
CD4 lymphocyte none	0.0	KU-812 (Basophil)	55.9
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	32.1	CCD1106 (Keratinocytes)	54.7
CH11		none
LAK cells rest	42.9	CCD1106 (Keratinocytes)	39.8
		TNF alpha + IL-1beta
LAK cells IL-2	40.6	Liver cirrhosis	14.9
LAK cells IL-2 + IL-12	46.0	NCI-H292 none	60.3
LAK cells IL-2 + IFN gamma	65.5	NCI-H292 IL-4	69.7
LAK cells IL-2 + IL-18	50.3	NCI-H292 IL-9	84.1
LAK cells PMA/ionomycin	52.9	NCI-H292 IL-13	48.6
NK Cells IL-2 rest	65.1	NCI-H292 IFN gamma	59.0
Two Way MLR 3 day	37.4	HPAEC none	48.3
Two Way MLR 5 day	55.1	HPAEC TNF alpha + IL-1	84.7
		beta
Two Way MLR 7 day	39.2	Lung fibroblast none	48.3
PBMC rest	23.2	Lung fibroblast TNF	59.5
		alpha + IL-1beta
PBMC PWM	45.4	Lung fibroblast IL-4	50.0
PBMC PHA-L	61.6	Lung fibroblast IL-9	68.8
Ramos (B cell) none	39.0	Lung fibroblast IL-13	56.3
Ramos (B cell) ionomycin	36.6	Lung fibroblast IFN gamma	100.0
B lymphocytes PWM	46.3	Dermal fibroblast CCD1070	80.7
		rest
B lymphocytes CD40L and	57.0	Dermal fibroblast CCD1070	88.9
IL-4		TNF alpha
EOL-1 dbcAMP	40.3	Dermal fibroblast CCD1070	35.6
		IL-1beta
EOL-1 dbcAMP	53.2	Dermal fibroblast IFN	46.7
PMA/ionomycin		gamma
Dendritic cells none	58.6	Dermal fibroblast IL-4	55.9
Dendritic cells LPS	49.7	Dermal Fibroblasts rest	41.8
Dendritic cells anti-CD40	58.6	Neutrophils TNF a + LPS	17.9
Monocytes rest	26.2	Neutrophils rest	19.5
Monocytes LPS	55.1	Colon	23.5
Macrophages rest	35.6	Lung	32.1
Macrophages LPS	37.9	Thymus	49.7
HUVEC none	49.3	Kidney	85.9
HUVEC starved	66.4

[0862] CNS_neurodegeneration_v1.0 Summary: Ag4445 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. See Panel 1.4 for discussion of this gene in the central nervous system.

[0863] General_screening_panel13v1.4 Summary: Ag4445 Highest expression of this gene is seen in a melanoma cell line (CT=22.4). This gene is widely expressed in this panel, with high levels of expression seen in brain, colon, gastric, lung, breast, ovarian, and melanoma cancer cell lines. In addition, this gene is expressed at higher levels in fetal lung (CT=25) when compared to expression in adult lung (CT=28). Thus, expression of this gene could be used to differentiate between the fetal and adult source of this tissue. This expression profile suggests a role for this gene product in cell survival and proliferation. Modulation of this gene product may be useful in the treatment of cancer.

[0864] Among tissues with metabolic function, this gene is expressed at high 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 function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0865] This gene is also expressed at high levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum 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.

[0866] Panel 4.1D Summary: Ag4445 Highest expression of this gene is seen in IFN gamma treated lung fibroblasts (CT=28.1). This gene is also 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 fimctions 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.

AF. CG59975-01 and CG59975-02: Q9NO61-like Protein

[0867] Expression of gene CG59975-01 and variant CG59975-02 was assessed using the primer-probe set Ag3640, described in Table AFA. Results of the RTQ-PCR runs are shown in Tables AFB, AFC, AFD and AFE. Please note that CG59975-02 represents a full-length physical clone, verifying the CG59975-01 gene prediction.

TABLE AFA
Probe Name Ag3640
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-tgtttcaatctttcctcctcaa-3′	22	463	183
Probe	TET-5′-catttcaagctttgtgctgcctcttg-3′-TAMRA	26	512	184
Reverse	5′-ccacctggacaaagaggtagat-3′	22	538	185

[0868]

TABLE AFB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag3640, Run		Ag3640, Run
Tissue Name	212315185	Tissue Name	212315185
AD 1 Hippo	9.1	Control (Path) 3 Temporal	8.7
		Ctx
AD 2 Hippo	32.3	Control (Path) 4 Temporal	34.9
		Ctx
AD 3 Hippo	8.1	AD 1 Occipital Ctx	20.4
AD 4 Hippo	8.7	AD 2 Occipital Ctx	0.0
		(Missing)
AD 5 Hippo	87.7	AD 3 Occipital Ctx	8.1
AD 6 Hippo	55.5	AD 4 Occipital Ctx	39.0
Control 2 Hippo	50.0	AD 5 Occipital Ctx	54.0
Control 4 Hippo	14.0	AD 6 Occipital Ctx	25.0
Control (Path) 3 Hippo	8.1	Control 1 Occipital Ctx	4.7
AD 1 Temporal Ctx	22.2	Control 2 Occipital Ctx	81.8
AD 2 Temporal Ctx	34.2	Control 3 Occipital Ctx	16.0
AD 3 Temporal Ctx	4.7	Control 4 Occipital Ctx	9.7
AD 4 Temporal Ctx	19.1	Control (Path) 1 Occipital	100.0
		Ctx
AD 5 Inf Temporal Ctx	98.6	Control (Path) 2 Occipital	12.1
		Ctx
AD 5 SupTemporal Ctx	36.3	Control (Path) 3 Occipital	3.5
		Ctx
AD 6 Inf Temporal Ctx	53.2	Control (Path) 4 Occipital	21.8
		Ctx
AD 6 Sup Temporal Ctx	44.4	Control 1 Parietal Ctx	10.4
Control 1 Temporal Ctx	7.0	Control 2 Parietal Ctx	43.5
Control 2 Temporal Ctx	51.4	Control 3 Parietal Ctx	22.1
Control 3 Temporal Ctx	16.3	Control (Path) 1 Parietal Ctx	95.9
Control 3 Temporal Ctx	12.0	Control (Path) 2 Parietal Ctx	33.9
Control (Path) 1 Temporal	67.4	Control (Path) 3 Parietal Ctx	4.0
Ctx
Control (Path) 2 Temporal	49.0	Control (Path) 4 Parietal Ctx	40.6
Ctx

[0869]

TABLE AFC
General_screening_panel_v1.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag3640, Run		Ag3640, Run
Tissue Name	218234165	Tissue Name	218234165
Adipose	13.1	Renal ca. TK-10	33.4
Melanoma* Hs688(A).T	51.1	Bladder	34.2
Melanoma* Hs688(B).T	41.8	Gastric ca. (liver met.) NCI-	63.3
		N87
Melanoma* M14	26.6	Gastric ca. KATO III	87.7
Melanoma* LOXIMVI	38.4	Colon ca. SW-948	11.6
Melanoma* SK-MEL-5	33.2	Colon ca. SW480	48.3
Squamous cell carcinoma	30.8	Colon ca.* (SW480 met)	23.2
SCC-4		SW620
Testis Pool	22.8	Colon ca. HT29	17.0
Prostate ca.* (bone met)	46.0	Colon ca. HCT-116	57.4
PC-3
Prostate Pool	18.6	Colon ca. CaCo-2	31.4
Placenta	13.9	Colon cancer tissue	29.7
Uterus Pool	4.9	Colon ca. SW1116	9.2
Ovarian ca. OVCAR-3	35.4	Colon ca. Colo-205	7.2
Ovarian ca. SK-OV-3	63.3	Colon ca. SW-48	15.6
Ovarian ca. OVCAR-4	24.8	Colon Pool	37.1
Ovarian ca. OVCAR-5	53.6	Small Intestine Pool	34.4
Ovarian ca. IGROV-1	24.3	Stomach Pool	27.2
Ovarian ca. OVCAR-8	15.0	Bone Marrow Pool	13.7
Ovary	19.5	Fetal Heart	18.7
Breast ca. MCF-7	63.3	Heart Pool	19.5
Breast ca. MDA-MB-231	66.4	Lymph Node Pool	40.1
Breast ca. BT 549	80.1	Fetal Skeletal Muscle	14.6
Breast ca. T47D	62.4	Skeletal Muscle Pool	19.1
Breast ca. MDA-N	21.0	Spleen Pool	18.9
Breast Pool	39.0	Thymus Pool	29.9
Trachea	32.5	CNS cancer (glio/astro)	39.5
		U87-MG
Lung	9.0	CNS cancer (glio/astro) U-	68.8
		118-MG
Fetal Lung	60.3	CNS cancer (neuro;met) SK-	29.3
		N-AS
Lung ca. NCI-N417	5.1	CNS cancer (astro) SF-539	15.5
Lung ca. LX-1	33.0	CNS cancer (astro) SNB-75	93.3
Lung ca. NCI-H146	39.5	CNS cancer (glio) SNB-19	20.6
Lung ca. SHP-77	57.0	CNS cancer (glio) SF-295	100.0
Lung ca. A549	31.6	Brain (Amygdala) Pool	24.5
Lung ca. NCI-H526	14.1	Brain (cerebellum)	38.4
Lung ca. NCI-H23	50.7	Brain (fetal)	49.7
Lung ca. NCI-H460	19.1	Brain (Hippocampus) Pool	27.9
Lung ca. HOP-62	30.8	Cerebral Cortex Pool	36.6
Lung ca. NCI-H522	26.1	Brain (Substantia nigra)	33.0
		Pool
Liver	2.4	Brain (Thalamus) Pool	39.8
Fetal Liver	22.7	Brain (whole)	29.9
Liver ca. HepG2	18.4	Spinal Cord Pool	24.7
Kidney Pool	55.5	Adrenal Gland	33.4
Fetal Kidney	37.9	Pituitary gland Pool	18.0
Renal ca. 786-0	35.8	Salivary Gland	9.9
Renal ca. A498	9.7	Thyroid (female)	16.3
Renal ca. ACHN	24.8	Pancreatic ca. CAPAN2	18.4
Renal ca. UO-31	45.4	Pancreas Pool	41.2

[0870]

TABLE AFD
Panel 4.1D
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag3640, Run		Ag3640, Run
Tissue Name	169975099	Tissue Name	169975099
Secondary Th1 act	30.4	HUVEC IL-1beta	42.6
Secondary Th2 act	49.7	HUVEC IFN gamma	49.0
Secondary Tr1 act	63.3	HUVEC TNF alpha + IFN	50.3
		gamma
Secondary Th1 rest	22.5	HUVEC TNF alpha + IL4	62.0
Secondary Th2 rest	39.5	HUVEC IL-11	15.8
Secondary Tr1 rest	38.2	Lung Microvascular EC	77.9
		none
Primary Th1 act	31.2	Lung Microvascular EC	84.7
		TNF alpha + IL-1beta
Primary Th2 act	42.0	Microvascular Dermal EC	51.1
		none
Primary Tr1 act	31.0	Microsvasular Dermal EC	34.4
		TNF alpha + IL-1beta
Primary Th1 rest	28.3	Bronchial epithelium	34.6
		TNF alpha + IL1beta
Primary Th2 rest	37.6	Small airway epithelium	20.4
		none
Primary Tr1 rest	59.0	Small airway epithelium	62.0
		TNF alpha + IL-1beta
CD45RA CD4 lymphocyte	46.7	Coronery artery SMC rest	27.7
act
CD45RO CD4 lymphocyte	37.9	Coronery artery SMC	35.6
act		TNF alpha + IL-1beta
CD8 lymphocyte act	42.3	Astrocytes rest	43.8
Secondary CD8 lymphocyte	34.2	Astrocytes TNF alpha + IL-	34.2
rest		1beta
Secondary CD8 lymphocyte	22.5	KU-812 (Basophil) rest	50.7
act
CD4 lymphocyte none	24.8	(KU-812 (Basophil)	100.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	32.3	CCD1106 (Keratinocytes)	50.7
CH11		none
LAK cells rest	42.9	CCD1106 (Keratinocytes)	42.6
		TNF alpha + IL-1beta
LAK cells IL-2	43.5	Liver cirrhosis	14.1
LAK cells IL-2 + IL-12	34.6	NCI-H292 none	30.4
LAK cells IL-2 + IFN gamma	62.4	NCI-H292 IL-4	50.3
LAK cells IL-2 + IL-18	67.4	NCI-H292 IL-9	65.1
LAK cells PMA/ionomycin	24.1	NCI-H292 IL-13	61.6
NK Cells IL-2 rest	48.3	NCI-H292 IFN gamma	47.3
Two Way MLR 3 day	62.0	HPAEC none	32.5
Two Way MLR 5 day	20.7	HPAEC TNF alpha + IL-1	70.7
		beta
Two Way MLR 7 day	18.4	Lung fibroblast none	40.9
PBMC rest	15.5	Lung fibroblast TNF alpha +	23.3
		IL-1beta
PBMC PWM	35.1	Lung fibroblast IL-4	52.1
PBMC PHA-L	29.3	Lung fibroblast IL-9	64.2
Ramos (B cell) none	36.9	Lung fibroblast IL-13	54.0
Ramos (B cell) ionomycin	34.2	Lung fibroblast IFN gamma	66.0
B lymphocytes PWM	31.4	Dermal fibroblast CCD1070	61.1
		rest
B lymphocytes CD40L and	55.9	Dermal fibroblast CCD1070	98.6
IL-4		TNF alpha
EOL-1 dbcAMP	58.6	Dermal fibroblast CCD1070	32.1
		IL-1beta
EOL-1 dbcAMP	74.2	Dermal fibroblast IFN	29.5
PMA/ionomycin		gamma
Dendritic cells none	34.4	Dermal fibroblast IL-4	43.5
Dendritic cells LPS	24.3	Dermal Fibroblasts rest	47.3
Dendritic cells anti-CD40	38.7	Neutrophils TNF a + LPS	2.0
Monocytes rest	49.3	Neutrophils rest	32.1
Monocytes LPS	95.3	Colon	16.6
Macrophages rest	33.0	Lung	16.0
Macrophages LPS	13.6	Thymus	74.2
HUVEC none	17.6	Kidney	41.5
HUVEC starved	41.5

[0871]

TABLE AFE
general oncology screening panel_v_2.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag3640, Run		Ag3640, Run
Tissue Name	267752338	Tissue Name	267752338
Colon cancer 1	35.4	Bladder cancer NAT 2	0.4
Colon cancer NAT 1	12.4	Bladder cancer NAT 3	0.4
Colon cancer 2	20.2	Bladder cancer NAT 4	11.6
Colon cancer NAT 2	16.7	Adenocarcinoma of the	61.1
		prostate 1
Colon cancer 3	39.8	Adenocarcinoma of the	6.5
		prostate 2
Colon cancer NAT 3	32.8	Adenocarcinoma of the	39.2
		prostate 3
Colon malignant cancer 4	56.3	Adenocarcinoma of the	31.2
		prostate 4
Colon normal adjacent	6.7	Prostate cancer NAT 5	6.8
tissue 4
Lung cancer 1	17.8	Adenocarcinoma of the	15.3
		prostate 6
Lung NAT 1	2.5	Adenocarcinoma of the	15.3
		prostate 7
Lung cancer 2	96.6	Adenocarcinoma of the	3.6
		prostate 8
Lung NAT 2	7.2	Adenocarcinoma of the	53.6
		prostate 9
Squamous cell carcinoma 3	45.4	Prostate cancer NAT 10	3.0
Lung NAT 3	1.2	Kidney cancer 1	39.5
metastatic melanoma 1	41.2	KidneyNAT 1	15.6
Melanoma 2	5.3	Kidney cancer 2	69.3
Melanoma 3	7.4	Kidney NAT 2	37.6
metastatic melanoma 4	100.0	Kidney cancer 3	30.1
metastatic melanoma 5	82.9	Kidney NAT 3	11.0
Bladder cancer 1	2.3	Kidney cancer 4	32.1
Bladder cancer NAT 1	0.0	Kidney NAT 4	13.1
Bladder cancer 2	12.5

[0872] CNS_neurodegeneration_v1.0 Summary: Ag3640 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. See Panel 1.4 for discussion of this gene in the central nervous system.

[0873] General_screening_panel13v1.4 Summary: Ag3640 Highest expression of this gene is seen in a brain cancer cell line (CT=26,7). This gene is widely expressed in this panel, with moderate expression seen in all cancer cell lines. In addition, this gene is expressed at much higher levels in fetal lung and liver tissue (CTs=27-29) when compared to expression in the adult counterpart (CTs=30-32). Thus, expression of this gene may be used to differentiate between the fetal and adult source of these tissues. This expression profile suggests a role for this gene product in cell survival and proliferation. Modulation of this gene product may be useful in the treatment of cancer.

[0874] 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 function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0875] This gene is also expressed at moderate levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum 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.

[0876] Panel 4.1D Summary: Ag3640 Highest expression of this gene is seen in the activated basophil cell line KU-812 (CT=27.5). This gene is also 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.

[0877] General oncology screening panel_v—2.4 Summary: Ag3640 This gene is widely expressed in this panel, with highest expression in melanoma (CT=27.7). In addition, this gene is more highly expressed in prostate, bladder, and kidney cancer than in the corresponding normal adjacent tissue. Thus, expression of this gene could be used as a marker of these cancers. Furthemore, therapeutic modulation of the expression or function of this gene product may be useful in the treatment of melanoma, prostate, bladder, and kidney cancer.

AG. CG89947-01 and CG89947-02: Stra8

[0878] Expression of gene CG89947-01 and variant CG89947-02 was assessed using the primer-probe set Ag3698, described in Table AGA. Please note that CG89947-02 represents a full-length physical clone, verifying the CG89947-01 gene prediction.

TABLE AGA
Probe Name Ag3698
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ctcttcaacaacctcaggaaga-3′	22	161	186
Probe	TET-5′-tgtactctcagtctgatctcatagcctca-3′-TAMRA	29	186	187
Reverse	5′-ccttattcagaacctgccactt-3′	22	215	188

AH. CG93366-02: Membrane Protein Kinase

[0879] Expression of gene CG93366-02 was assessed using the primer-probe set Ag3851, described in Table AHA. Results of the RTQ-PCR runs are shown in Tables AHB, AHC, AHD and AHE.

TABLE AHA
Probe Name Ag3851
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ttgaaagatgttggtggagaag-3′	22	985	189
Probe	TET-5′-ccagtctaatttacctcattcaaacagca-3′-TAMRA	29	1032	190
Reverse	5′-gcagctgcagacaactcatta-3′	21	1062	140

[0880]

TABLE AHB
CNS_neurodegeneration_v1.0
                           Rel. Exp. (%)
                           Ag3851, Run
Tissue Name                212186804
AD 1 Hippo                 19.2
AD 2 Hippo                 37.4
AD 3 Hippo                 10.2
AD 4 Hippo                 10.5
AD 5 hippo                 90.8
AD 6 Hippo                 52.9
Control 2 Hippo            29.5
Control 4 Hippo            22.8
Control (Path) 3 Hippo     12.8
AD 1 Temporal Ctx          27.2
AD 2 Temporal Ctx          49.3
AD 3 Temporal Ctx          12.9
AD 4 Temporal Ctx          33.2
AD 5 Inf Temporal Ctx      100.0
AD 5 SupTemporal Ctx       62.4
AD 6 Inf Temporal Ctx      71.2
AD 6 Sup Temporal Ctx      59.9
Control 1 Temporal Ctx     11.6
Control 2 Temporal Ctx     40.6
Control 3 Temporal Ctx     22.4
Control 4 Temporal Ctx     16.5
Control (Path) 1 Temporal  76.3
Ctx
Control (Path) 2 Temporal  51.8
Ctx
Control (Path) 3 Temporal  10.8
Ctx
Control (Path) 4 Temporal  50.7
Ctx
AD 1 Occipital Ctx         34.2
AD 2 Occipital Ctx         0.0
(Missing)
AD 3 Occipital Ctx         13.4
AD 4 Occipital Ctx         24.7
AD 5 Occipital Ctx         25.0
AD 6 Occipital Ctx         45.7
Control 1 Occipital Ctx    6.5
Control 2 Occipital Ctx    65.5
Control 3 Occipital Ctx    26.4
Control 4 Occipital Ctx    12.5
Control (Path) 1 Occipital 95.3
Ctx
Control (Path) 2 Occipital 23.0
Ctx
Control (Path) 3 Occipital 6.5
Ctx
Control (Path) 4 Occipital 26.8
Ctx
Control 1 Parietal Ctx     11.8
Control 2 Parietal Ctx     58.6
Control 3 Parietal Ctx     23.8
Control (Path) 1 Parietal  89.5
Ctx
Control (Path) 2 Parietal  37.9
Ctx
Control (Path) 3 Parietal  7.3
Ctx
Control (Path) 4 Parietal  57.0
Ctx

[0881]

TABLE AHC
General screening panel v1.4
                                 Rel. Exp. (%)
                                 Ag3851, Run
Tissue Name                      213603718
Adipose                          22.8
Melanoma* Hs688(A).T             62.4
Melanoma* Hs688(B).T             51.1
Melanoma* M14                    14.8
Melanoma* LOXIMVI                6.7
Melanoma* SK-MEL-5               30.1
Squamous cell carcinoma          24.8
SCC-4
Testis Pool                      20.4
Prostate ca.* (bone met) PC-3    26.8
Prostate Pool                    15.5
Placenta                         3.8
Uterus Pool                      12.7
Ovarian ca. OVCAR-3              32.5
Ovarian ca. SK-OV-3              75.3
Ovarian ca. OVCAR-4              17.2
Ovarian ca. OVCAR-5              54.0
Ovarian ca. IGROV-1              20.7
Ovarian ca. OVCAR-8              11.8
Ovary                            26.1
Breast ca. MCF-7                 35.1
Breast ca. MDA-MB-23             19.5
Breast ca. BT 549                33.0
Breast ca. T47D                  79.0
Breast ca. MDA-N                 12.3
Breast Pool                      38.2
Trachea                          14.3
Lung                             13.3
Fetal Lung                       53.2
Lung ca. NCI-N417                3.7
Lung ca. LX-1                    40.6
Lung ca. NCI-H146                5.1
Lung ca. SHP-77                  29.7
Lung ca. A549                    25.3
Lung ca. NCI-H526                5.8
Lung ca. NCI-H23                 90.8
Lung ca. NCI-H460                32.5
Lung ca. HOP-62                  31.6
Lung ca. NCI-H522                24.5
Liver                            0.7
Fetal Liver                      47.6
Liver ca. HepG2                  50.0
Kidney Pool                      50.0
Fetal Kidney                     51.1
Renal ca. TK-10                  41.2
Bladder                          23.3
Gastric ca. (liver met.) NCI-N87 44.8
Gastric ca. KATO III             27.4
Colon ca. SW-948                 6.3
Colon ca. SW480                  24.1
Colon ca.* (SW480 met)           14.9
SW620
Colon ca. HT29                   14.8
Colon ca. HCT-116                32.8
Colon ca. CaCo-2                 55.9
Colon cancer tissue              15.2
Colon ca. SW1116                 4.0
Colon ca. Colo-205               5.3
Colon ca. SW-48                  7.0
Colon Pool                       29.7
Small Intestine Pool             25.5
Stomach Pool                     29.3
Bone Marrow Pool                 8.1
Fetal Heart                      12.2
Heart Pool                       11.6
Lymph Node Pool                  32.8
Fetal Skeletal Muscle            10.6
Skeletal Muscle Pool             16.8
Spleen Pool                      28.7
Thymus Pool                      33.7
CNS cancer (glio/astro)          38.2
U87-MG
CNS cancer (glio/astro) U-       36.9
118-MG
CNS cancer (neuro; met)          55.9
SK-N-AS
CNS cancer (astro) SF-539        10.7
CNS cancer (astro) SNB-75        21.9
CNS cancer (glio) SNB-19         15.8
CNS cancer (glio) SF-295         100.0
Brain (Amygdala) Pool            13.3
Brain (cerebellum)               19.2
Brain (fetal)                    40.9
Brain (Hippocampus) Pool         20.9
Cerebral Cortex Pool             21.9
Brain (Substantia nigra)         23.8
Pool
Brain (Thalamus) Pool            31.2
Brain (whole)                    23.0
Spinal Cord Pool                 19.2
Adrenal Gland                    10.4
Pituitary gland Pool             10.7
Renal ca. 786-0                  39.0
Renal ca. A498                   12.9
Renal ca. ACHN                   15.9
Renal ca. UO-31                  42.0
Salivary Gland                   5.3
Thyroid (female)                 11.7
Pancreatic ca. CAPAN2            36.3
Pancreas Pool                    52.5

[0882]

TABLE AHD
Panel 4.1D
                            Rel. Exp. (%)
                            Ag3851, Run
Tissue Name                 170121368
Secondary Th1 act           42.3
Secondary Th2 act           74.7
Secondary Tr1 act           84.7
Secondary Th1 rest          23.0
Secondary Th2 rest          52.5
Secondary Tr1 rest          40.6
Primary Th1 act             53.2
Primary Th2 act             55.9
Primary Tr1 act             39.5
Primary Th1 rest            37.4
Primary Th2 rest            62.0
Primary Tr1 rest            66.4
CD45RA CD4 lymphocyte       35.6
act
CD45RO CD4 lymphocyte       65.5
act
CD8 lymphocyte act          67.8
Secondary CD8 lymphocyte    33.9
rest
Secondary CD8 lymphocyte    21.0
act
CD4 lymphocyte none         42.3
2ry Th1/Th2/Tr1 anti-CD95   51.8
CH11
LAK cells rest              46.3
LAK cells IL-2              54.0
LAK cells IL-2 + IL-12      57.0
LAK cells IL-2 + IFN gamma  77.9
LAK cells IL-2 + IL- 18     78.5
LAK cells PMA/ionomycin     27.4
NK Cells IL-2 rest          54.3
Two Way MLR 3 day           80.7
Two Way MLR 5 day           41.2
Two Way MLR 7 day           31.2
PBMC rest                   37.1
PBMC PWM                    42.6
PBMC PHA-L                  54.7
Ramos (B cell) none         47.3
Ramos (B cell) ionomycin    41.8
B lymphocytes PWM           37.9
B lymphocytes CD40L and     72.2
IL-4
EOL-1 dbcAMP                76.8
EOL-1 dbcAMP                100.0
PMA/ionomycin
Dendritic cells none        57.4
Dendritic cells LPS         30.4
Dendritic cells anti-CD40   61.1
Monocytes rest              51.8
Monocytes LPS               38.7
Macrophages rest            49.7
Macrophages LPS             14.5
HUVEC none                  24.0
HUVEC starved               31.9
HUVEC IL-1beta              39.0
HUVEC IFN gamma             65.1
HUVEC TNF alpha + IFN       27.2
gamma
HUVEC TNF alpha + IL4       29.3
HUVEC IL- 11                24.5
Lung Microvascular EC       76.8
none
Lung Microvascular EC       44.4
TNFalpha + IL-1beta
Microvascular Dermal EC     45.4
none
Microsvasular Dermal EC     36.6
TNFalpha + IL-1beta
Bronchial epithelium        42.3
TNFalpha + IL-1beta
Small airway epithelium     14.2
none
Small airway epithelium     33.7
TNFalpha + IL-1beta
Coronery artery SMC rest    33.7
Coronery artery SMC         30.4
TNF alpha + IL-1beta
Astrocytes rest             41.2
Astrocytes TNF alpha + IL-  21.0
1beta
KU-812 (Basophil)rest       52.5
KU-812 (Basophil)           99.3
PMA/ionomycin
CCD1106 (Keratinocytes)     26.2
none
CCD1106 (Keratinocytes)     39.0
TNFalpha + IL-1beta
Liver cirrhosis             18.9
NCI-H292 none               43.2
NCI-H292 IL-4               42.6
NCI-H292 IL-9               71.2
NCI-H292 IL-13              68.8
NCI-H292 IFN gamma          71.7
HPAEC none                  38.7
HPAEC TNF alpha + IL-1      47.0
beta
Lung fibroblast none        54.3
Lung fibroblast TNF alpha + 20.9
IL-1 beta
Lung fibroblast IL-4        56.6
Lung fibroblast IL-9        76.8
Lung fibroblast IL-13       50.0
Lung fibroblast IFN gamma   56.6
Dermal fibroblast CCD1070   33.0
rest
Dermal fibroblast CCD1070   62.4
TNF alpha
Dermal fibroblast CCD1070   21.3
IL-1 beta
Dermal fibroblast IFN       36.1
gamma
Dermal fibroblast IL-4      82.4
Dermal Fibroblasts rest     65.5
Neutrophils TNFa + LPS      0.7
Neutrophils rest            8.3
Colon                       16.4
Lung                        33.7
Thymus                      84.7
Kidney                      78.5

[0883]

TABLE AHE
general oncology screening panel_v_2.4
                               Rel. Exp. (%)
                               Ag3851, Run
Tissue Name                    268036588
Colon cancer 1                 21.6
Colon cancer NAT 1             7.8
Colon cancer 2                 10.7
Colon cancer NAT 2             10.2
Colon cancer 3                 21.9
Colon cancer NAT 3             15.6
Colon malignant cancer 4       31.2
Colon normal adjacent tissue 4 4.9
Lung cancer 1                  8.7
Lung NAT 1                     2.9
Lung cancer 2                  39.5
Lung NAT 2                     4.1
Squamous cell carcinoma 3      18.0
Lung NAT 3                     0.5
metastatic melanoma 1          35.6
Melanoma 2                     1.2
Melanoma 3                     4.1
metastatic melanoma 4          66.0
metastatic melanoma 5          100.0
Bladder cancer 1               2.7
Bladder cancer NAT 1           0.0
Bladder cancer 2               8.8
Bladder cancer NAT 2           1.1
Bladder cancer NAT 3           0.5
Bladder cancer NAT 4           4.2
Adenocarcinoma of the          57.4
prostate 1
Adenocarcinoma of the          3.5
prostate 2
Adenocarcinoma of the          16.4
prostate 3
Adenocarcinoma of the          14.7
prostate 4
Prostate cancer NAT 5          1.9
Adenocarcinoma of the          4.0
prostate 6
Adenocarcinoma of the          5.8
prostate 7
Adenocarcinoma of the          2.2
prostate 8
Adenocarcinoma of the          33.9
prostate 9
Prostate cancer NAT 10         2.2
Kidney cancer 1                21.3
Kidney NAT 1                   12.6
Kidney cancer 2                32.1
Kidney NAT 2                   27.2
Kidney cancer 3                34.4
Kidney NAT 3                   10.4
Kidney cancer 4                16.0
Kidney NAT 4                   6.3

[0884] CNS_neurodegeneration_v1.0 Summary: Ag3851 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. See Panel 1.4 for discussion of this gene in the central nervous system.

[0885] General_screening_panel13v1.4 Summary: Ag3851 Highest expression of this gene is seen in a brain cancer cell line (CT=26.5). This gene is widely expressed in this panel, with high to moderate expression seen in brain, colon, gastric, lung, breast, ovarian, and melanoma cancers. This expression profile suggests a role for this gene product in cell survival and proliferation. Modulation of this gene product may be useful in the treatment of cancer.

[0886] 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 function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0887] This gene is also expressed at moderate levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum 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.

[0888] In addition, this gene is expressed at much higher levels in fetal liver tissue (CT=27.5) when compared to expression in the adult counterpart (CT=33.7). Thus, expression of this gene may be used to differentiate between the fetal and adult source of this tissue. The relative overexpression of this gene in fetal liver suggests that the protein product may enhance growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of this gene could be useful in treatment of liver disease.

[0889] Panel 4.1D Summary: Ag3851 This gene is expressed at moderate levels in a wide range of cell types of significance in the immune response in health and disease, with highest expression in activated eosinophils (CT=28.8). 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_panel13v1.4 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.

[0890] General oncology screening panel_v—2.4 Summary: Ag3851 Highest expression of this gene is seen in melanoma (CT=26.5). In addition, higher levels of expression of this gene are seen in lung, colon, and prostate cancer when compared to expression in normal adjacent tissue. Thus, expression of this gene could be used as a marker of these cancers. Furthemore, therapeutic modulation of the expression or function of this gene product may be useful in the treatment of lung, colon and prostate cancer.

Example D

[0891] Identification of Single Nucleotide Polymorphisms in NOVX Nucleic Acid Sequences

[0892] 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.

[0893] 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.

[0894] 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.

[0895] 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).

[0896] 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.

[0897] SNPs for NOV6a Cytosolic Phosphoprotein Protein (CG101904-01)

	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13377350	197	T	C	26	Val	Ala
13379270	1640	G	A	507	Arg	His

[0898] SNPs for NOV9a NEURABIN 1-like Homo sapiens Proteins (CG102595-01)

	Nucleotides	Amino Acids
Variant	Base Position of			Base Position of
No.	SNP	Wild-type	Variant	SNP	Wild-type	Variant
13379218	3159	A	G	1033	Thr	Thr
13379217	3267	A	G	1069	Leu	Leu

[0899] SNPs for NOV11a Septin 6 (KIAA0128)-like Protein (CG102801-01)

	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13379273	876	G	A	269	Cys	Tyr
13379274	1032	A	G	321	Gln	Arg

[0900] SNPs NOV12a RIM24C-like Homo sapiens Proteins (CG102899-01)

	Nucleotides	Amino Acids
Variant	Base Position of			Base Position of
No.	SNP	Wild-type	Variant	SNP	Wild-type	Variant
13379220	3993	T	C	1311	Ala	Ala

[0901] SNPs for NOV13a Cell Growth Regulator Falkor-like Protein (CG105284-01)

	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13377532	187	C	A	46	Pro	Thr
13377533	1142	A	G	364	Tyr	Cys

[0902] SNPs for NOV17a Ankyrin-like Q9GKW8-like Homo sapiens Protein (CG105638-01)

	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13379275	100	A	T	22	Arg	Trp
13379276	217	C	T	61	His	Tyr
13379277	827	A	G	264	His	Arg

[0903] SNPs for NOV22a Amyloid Beta A4 Precursor Protein-Binding Family B Member 2-like Homo sapiens Protein (CG106868-01)

	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13379281	685	G	A	179	Arg	Gln

[0904] SPNs for NOV 26a Intracellular Signaling Protein-like Homo sapiens Proteins (CG109649-01)

	Nucleotides	Amino Acids
Variant	Base Position of			Base Position of
No.	SNP	Wild-type	Variant	SNP	Wild-type	Variant
13379254	228	C	T	56	Thr	Thr
13379253	300	C	T	80	Ile	Ile

[0905] SPNs for NOV31a VP3 Domain-containing Protein-like Homo sapiens Proteins (CG110063-01)

	Nucleotides	Amino Acids
Variant	Base Position of			Base Position of
No.	SNP	Wild-type	Variant	SNP	Wild-type	Variant
13379257	68	T	C	12	Pro	Pro
13379258	470	G	T	146	Leu	Phe

[0906] SNPs for NOV37a Stra8-like Homo sapiens Proteins (CG89947-01)

	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13375011	86	C	T	21	Gln	End
13375012	160	G	A	45	Ala	Ala
13375013	176	A	G	51	Arg	Gly

[0907] SNPs for NOV38a Membrane Protein Kinase-like Proteins (CG93366-02)

	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13379282	1656	C	T	552	Gly	Gly

Other Embodiments

[0908] 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.

[0909] 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 the mature form of an amino acid sequenced selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 44.

2. An isolated polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 44.

3. An isolated polypeptide comprising an amino acid sequence which is at least 95% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 44.

4. An isolated polypeptide, wherein the polypeptide comprises an amino acid sequence comprising one or more conservative substitutions in the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 44.

5. The polypeptide of claim 1 wherein said polypeptide is naturally occurring.

6. A composition comprising the polypeptide of claim 1 and a carrier.

7. A kit comprising, in one or more containers, the composition of claim 6.

8. The use of a therapeutic in the manufacture of a medicament for treating a syndrome associated with a human disease, the disease selected from a pathology associated with the polypeptide of claim 1, wherein the therapeutic comprises the polypeptide of claim 1.

9. 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.

10. A method for determining the presence of or predisposition to a disease associated with altered levels of expression 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 expression of said polypeptide in the sample of step (a) to the expression 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 level of expression of the polypeptide in the first subject as compared to the control sample indicates the presence of or predisposition to said disease.

11. 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.

12. The method of claim 11 wherein the agent is a cellular receptor or a downstream effector.

13. 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 in the absence of the substance, the substance is identified as a potential therapeutic agent.

14. A method for screening for a modulator of activity of 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 polypeptide 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 activity of or latency or predisposition to, a pathology associated with the polypeptide of claim 1.

15. The method of claim 14, wherein said test animal is a recombinant test animal that expresses a test protein transgene or expresses said transgene under the control of a promoter at an increased level relative to a wild-type test animal, and wherein said promoter is not the native gene promoter of said transgene.

16. A method for modulating the activity of the polypeptide of claim 1, the method comprising contacting a cell sample expressing the polypeptide of claim 1 with a compound that binds to said polypeptide in an amount sufficient to modulate the activity of the polypeptide.

17. A method of treating or preventing a pathology associated with the polypeptide of claim 1, the method comprising administering the polypeptide of claim 1 to a subject in which such treatment or prevention is desired in an amount sufficient to treat or prevent the pathology in the subject.

18. The method of claim 17, wherein the subject is a human.

19. A method of treating a pathological state in a mammal, the method comprising administering to the mammal a polypeptide in an amount that is sufficient to alleviate the pathological state, wherein the polypeptide is a polypeptide having an amino acid sequence at least 95% identical to 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 44, or a biologically active fragment thereof.

20. An isolated nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44.

21. The nucleic acid molecule of claim 20, wherein the nucleic acid molecule is naturally occurring.

22. A nucleic acid molecule, 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 44.

23. An isolated nucleic acid molecule encoding the mature form of a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 44.

24. An isolated nucleic acid molecule comprising a nucleic acid selected from the group consisting of 2n-1, wherein n is an integer between 1 and 44.

25. The nucleic acid molecule of claim 20, 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 44, or a complement of said nucleotide sequence.

26. A vector comprising the nucleic acid molecule of claim 20.

27. The vector of claim 26, further comprising a promoter operably linked to said nucleic acid molecule.

28. A cell comprising the vector of claim 26.

29. An antibody that immunospecifically binds to the polypeptide of claim 1.

30. The antibody of claim 29, wherein the antibody is a monoclonal antibody.

31. The antibody of claim 29, wherein the antibody is a humanized antibody.

32. A method for determining the presence or amount of the nucleic acid molecule of claim 20 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.

33. The method of claim 32 wherein presence or amount of the nucleic acid molecule is used as a marker for cell or tissue type.

34. The method of claim 33 wherein the cell or tissue type is cancerous.

35. A method for determining the presence of or predisposition to a disease associated with altered levels of expression of the nucleic acid molecule of claim 20 in a first mammalian subject, the method comprising: a) measuring the level of expression of the nucleic acid in a sample from the first mammalian subject; and b) comparing the level of expression of said nucleic acid in the sample of step (a) to the level of expression 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 expression of the nucleic acid in the first subject as compared to the control sample indicates the presence of or predisposition to the disease.

36. A method of producing the polypeptide of claim 1, the method comprising culturing a cell under conditions that lead to expression of the polypeptide, wherein said cell comprises a vector comprising an isolated nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44.

37. The method of claim 36 wherein the cell is a bacterial cell.

38. The method of claim 36 wherein the cell is an insect cell.

39. The method of claim 36 wherein the cell is a yeast cell.

40. The method of claim 36 wherein the cell is a mammalian cell.

41. A method of producing the polypeptide of claim 2, the method comprising culturing a cell under conditions that lead to expression of the polypeptide, wherein said cell comprises a vector comprising an isolated nucleic acid molecule comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO:2n-1, wherein n is an integer between 1 and 44.

42. The method of claim 41 wherein the cell is a bacterial cell.

43. The method of claim 41 wherein the cell is an insect cell.

44. The method of claim 41 wherein the cell is a yeast cell.

45. The method of claim 41 wherein the cell is a mammalian cell.