Novel proteins and nucleic acids encoding same

Abstract

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

Description

FIELD OF THE INVENTION

[0002] The present invention relates to novel polypeptides that are targets of small molecule drugs and that have properties related to stimulation of biochemical or physiological responses in a cell, a tissue, an organ or an organism. More particularly, the novel polypeptides are gene products of novel genes, or are specified biologically active fragments or derivatives thereof. Methods of use encompass diagnostic and prognostic assay procedures as well as methods of treating diverse pathological conditions.

BACKGROUND

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

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

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

[0006] Many pathological conditions involve dysregulation of expression of important effector proteins. In certain classes of pathologies the dysregulation is manifested as diminished or suppressed level of synthesis and secretion of protein effectors. In other classes of pathologies the dysregulation is manifested as increased or up-regulated level of synthesis and secretion of protein effectors. In a clinical setting a subject may be suspected of suffering from a condition brought on by altered or mis-regulated levels of a protein effector of interest. Therefore there is a need to assay for the level of the protein effector of interest in a biological sample from such a subject, and to compare the level with that characteristic of a nonpathological condition. There also is a need to provide the protein effector as a product of manufacture. Administration of the effector to a subject in need thereof is useful in treatment of the pathological condition. Accordingly, there is a need for a method of treatment of a pathological condition brought on by a diminished or suppressed levels of the protein effector of interest. In addition, there is a need for a method of treatment of a pathological condition brought on by a increased or up-regulated levels of the protein effector of interest.

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

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

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

SUMMARY OF THE INVENTION

[0010] The invention includes nucleic acid sequences and the novel polypeptides they encode. The novel nucleic acids and polypeptides are referred to herein as NOVX, or NOV1, NOV2, NOV3, etc., nucleic acids and polypeptides. These nucleic acids and polypeptides, as well as derivatives, homologs, analogs and fragments thereof, will hereinafter be collectively designated as “NOVX” nucleic acid, which represents the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 110, or polypeptide sequences, which represents the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 110.

[0011] In one aspect, the invention provides an isolated polypeptide comprising a mature form of a NOVX amino acid. One example is a variant of a mature form of a NOVX amino acid sequence, wherein any amino acid in the mature form is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed. The amino acid can be, for example, a NOVX amino acid sequence or a variant of a NOVX amino acid sequence, wherein any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed. The invention also includes fragments of any of these. In another aspect, the invention also includes an isolated nucleic acid that encodes a NOVX polypeptide, or a fragment, homolog, analog or derivative thereof.

[0012] Also included in the invention is a NOVX polypeptide that is a naturally occurring allelic variant of a NOVX sequence. In one embodiment, the allelic variant includes an amino acid sequence that is the translation of a nucleic acid sequence differing by a single nucleotide from a NOVX nucleic acid sequence. In another embodiment, the NOVX polypeptide is a variant polypeptide described therein, wherein any amino acid specified in the chosen sequence is changed to provide a conservative substitution. In one embodiment, the invention discloses a method for determining the presence or amount of the NOVX polypeptide in a sample. The method involves the steps of: providing a sample; introducing the sample to an antibody that binds immunospecifically to the polypeptide; and determining the presence or amount of antibody bound to the NOVX polypeptide, thereby determining the presence or amount of the NOVX polypeptide in the sample. In another embodiment, the invention provides a method for determining the presence of or predisposition to a disease associated with altered levels of a NOVX polypeptide in a mammalian subject. This method involves the steps of: measuring the level of expression of the polypeptide in a sample from the first mammalian subject; and comparing the amount of the polypeptide in the sample of the first step to the amount of the polypeptide present in a control sample from a second mammalian subject known not to have, or not to be predisposed to, the disease, wherein an alteration in the expression level of the polypeptide in the first subject as compared to the control sample indicates the presence of or predisposition to the disease.

[0013] In a further embodiment, the invention includes a method of identifying an agent that binds to a NOVX polypeptide. This method involves the steps of: introducing the polypeptide to the agent; and determining whether the agent binds to the polypeptide. In various embodiments, the agent is a cellular receptor or a downstream effector.

[0014] In another aspect, the invention provides a method for identifying a potential therapeutic agent for use in treatment of a pathology, wherein the pathology is related to aberrant expression or aberrant physiological interactions of a NOVX polypeptide. The method involves the steps of: providing a cell expressing the NOVX polypeptide and having a property or function ascribable to the polypeptide; contacting the cell with a composition comprising a candidate substance; and determining whether the substance alters the property or function ascribable to the polypeptide; whereby, if an alteration observed in the presence of the substance is not observed when the cell is contacted with a composition devoid of the substance, the substance is identified as a potential therapeutic agent. In another aspect, the invention describes a method for screening for a modulator of activity or of latency or predisposition to a pathology associated with the NOVX polypeptide. This method involves the following steps: administering a test compound to a test animal at increased risk for a pathology associated with the NOVX polypeptide, wherein the test animal recombinantly expresses the NOVX polypeptide. This method involves the steps of measuring the activity of the NOVX polypeptide in the test animal after administering the compound of step; and comparing the activity of the protein in the test animal with the activity of the NOVX polypeptide in a control animal not administered the polypeptide, wherein a change in the activity of the NOVX polypeptide in the test animal relative to the control animal indicates the test compound is a modulator of latency of, or predisposition to, a pathology associated with the NOVX polypeptide. In one embodiment, the test animal is a recombinant test animal that expresses a test protein transgene or expresses the transgene under the control of a promoter at an increased level relative to a wild-type test animal, and wherein the promoter is not the native gene promoter of the transgene. In another aspect, the invention includes a method for modulating the activity of the NOVX polypeptide, the method comprising introducing a cell sample expressing the NOVX polypeptide with a compound that binds to the polypeptide in an amount sufficient to modulate the activity of the polypeptide.

[0015] The invention also includes an isolated nucleic acid that encodes a NOVX polypeptide, or a fragment, homolog, analog or derivative thereof. In a preferred embodiment, the nucleic acid molecule comprises the nucleotide sequence of a naturally occurring allelic nucleic acid variant. In another embodiment, the nucleic acid encodes a variant polypeptide, wherein the variant polypeptide has the polypeptide sequence of a naturally occurring polypeptide variant. In another embodiment, the nucleic acid molecule differs by a single nucleotide from a NOVX nucleic acid sequence. In one embodiment, the NOVX nucleic acid molecule hybridizes under stringent conditions to the nucleotide sequence selected from the group consisting of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 110, or a complement of the nucleotide sequence. In another aspect, the invention provides a vector or a cell expressing a NOVX nucleotide sequence.

[0016] In one embodiment, the invention discloses a method for modulating the activity of a NOVX polypeptide. The method includes the steps of: introducing a cell sample expressing the NOVX polypeptide with a compound that binds to the polypeptide in an amount sufficient to modulate the activity of the polypeptide. In another embodiment, the invention includes an isolated NOVX nucleic acid molecule comprising a nucleic acid sequence encoding a polypeptide comprising a NOVX amino acid sequence or a variant of a mature form of the NOVX amino acid sequence, wherein any amino acid in the mature form of the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence of the mature form are so changed. In another embodiment, the invention includes an amino acid sequence that is a variant of the NOVX amino acid sequence, in which any amino acid specified in the chosen sequence is changed to a different amino acid, provided that no more than 15% of the amino acid residues in the sequence are so changed.

[0017] In one embodiment, the invention discloses a NOVX nucleic acid fragment encoding at least a portion of a NOVX polypeptide or any variant of the polypeptide, wherein any amino acid of the chosen sequence is changed to a different amino acid, provided that no more than 10% of the amino acid residues in the sequence are so changed. In another embodiment, the invention includes the complement of any of the NOVX nucleic acid molecules or a naturally occurring allelic nucleic acid variant. In another embodiment, the invention discloses a NOVX nucleic acid molecule that encodes a variant polypeptide, wherein the variant polypeptide has the polypeptide sequence of a naturally occurring polypeptide variant. In another embodiment, the invention discloses a NOVX nucleic acid, wherein the nucleic acid molecule differs by a single nucleotide from a NOVX nucleic acid sequence.

[0018] In another aspect, the invention includes a NOVX nucleic acid, wherein one or more nucleotides in the NOVX nucleotide sequence is changed to a different nucleotide provided that no more than 15% of the nucleotides are so changed. In one embodiment, the invention discloses a nucleic acid fragment of the NOVX nucleotide sequence and a nucleic acid fragment wherein one or more nucleotides in the NOVX nucleotide sequence is changed from that selected from the group consisting of the chosen sequence to a different nucleotide provided that no more than 15% of the nucleotides are so changed. In another embodiment, the invention includes a nucleic acid molecule wherein the nucleic acid molecule hybridizes under stringent conditions to a NOVX nucleotide sequence or a complement of the NOVX nucleotide sequence. In one embodiment, the invention includes a nucleic acid molecule, wherein the sequence is changed such that no more than 15% of the nucleotides in the coding sequence differ from the NOVX nucleotide sequence or a fragment thereof.

[0019] In a further aspect, the invention includes a method for determining the presence or amount of the NOVX nucleic acid in a sample. The method involves the steps of: providing the sample; introducing the sample to a probe that binds to the nucleic acid molecule; and determining the presence or amount of the probe bound to the NOVX nucleic acid molecule, thereby determining the presence or amount of the NOVX nucleic acid molecule in the sample. In one embodiment, the presence or amount of the nucleic acid molecule is used as a marker for cell or tissue type.

[0020] In another aspect, the invention discloses a method for determining the presence of or predisposition to a disease associated with altered levels of the NOVX nucleic acid molecule of in a first mammalian subject. The method involves the steps of: measuring the amount of NOVX nucleic acid in a sample from the first mammalian subject; and comparing the amount of the nucleic acid in the sample of step (a) to the amount of NOVX nucleic acid present in a control sample from a second mammalian subject known not to have or not be predisposed to, the disease; wherein an alteration in the level of the nucleic acid in the first subject as compared to the control sample indicates the presence of or predisposition to the disease.

[0021] 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.

[0022] Other features and advantages of the invention will be apparent from the following detailed description and claims.

BRIEF DESCRIPTION OF THE FIGURES

[0023] FIG. 1 shows the x-ray crystal structure of trypsin 1 at a 2.2 Å resolution (Gaboriaud, C. et. al, Jol. Mol. Biol., 1996, 259:995-1010)(PDB code 1TRN). The sequences absent in the CG59482-02 splice variant are denoted by short arrows. The view in FIG. 1 shows the active site facing outward with a diisopropyl-phosphofluoridate inhibitor in the active site (indicated by long arrows).

[0024] FIG. 2 shows the three residues which form the catalytic triad of the active site.

[0025] FIG. 3 depicts a proposed mechanism for catalytic triad formation. The pKa for the serine hydroxyl is usually about 13, which makes it a poor nucleophile. The aspartate, histidine and serine are arranged in a charge relay system of hydrogen bonds that helps to lower this pKa, which makes the sidechain more reactive. The carboxyl side chain on aspartate attracts a proton from histidine, which in turn abstracts a proton from the hydroxyl of serine allowing it to react with and then cleave the polypeptide substrate.

DETAILED DESCRIPTION OF THE INVENTION

[0026] The present invention provides novel nucleotides and polypeptides encoded thereby. Included in the invention are the novel nucleic acid sequences, their encoded polypeptides, antibodies, and other related compounds. The sequences are collectively referred to herein as “NOVX nucleic acids” or “NOVX polynucleotides” and the corresponding encoded polypeptides are referred to as “NOVX polypeptides” or “NOVX proteins.” Unless indicated otherwise, “NOVX” is meant to refer to any of the novel sequences disclosed herein. Table A provides a summary of the NOVX nucleic acids and their encoded polypeptides.

TABLE A
Sequences and Corresponding SEQ ID Numbers
		SEQ	SEQ
		ID NO	ID NO
NOVX	Internal	(nucleic	(amino
Assignment	Identification	acid)	acid)	Homology
1a	CG105324-01	1	2	Nuclear Orphan receptor LXR alpha protein
1b	212779039	3	4	Human nuclear orphan receptor LXR-alpha-
				like Proteins
1c	CG105324-01	5	6	Human nuclear orphan receptor LXR-alpha-
				like Proteins
1d	209829541	7	8	Human nuclear orphan receptor LXR-alpha-
				like Proteins
2a	CG105355-01	9	10	Nuclear Aryl Hydrocarbon receptor protein
2b	245279626	11	12	Aryl hydrocarbon receptor- like Proteins
2c	CG105355-02	13	14	Aryl hydrocarbon receptor- like Proteins
2d	CG105355-03	15	16	Aryl hydrocarbon receptor- like Proteins
3a	CG105521-01	17	18	stearoyl CoA desaturase protein
3b	CG105521-02	19	20	stearoyl CoA desaturase protein
3c	301113881	21	22	stearoyl CoA desaturase protein
3d	CG105521-01	23	24	Stearoyl CoA desaturase protein
3e	309330043	25	26	Stearoyl CoA desaturase protein
3f	309330069	27	28	Stearoyl CoA desaturase protein
3g	CG105521-01	29	30	Stearoyl CoA desaturase -like protein
3h	212779051	31	32	Stearoyl CoA desaturase -like protein
3i	CG105521-01	33	34	Stearoyl CoA desaturase- like protein
3j	308782133	35	36	Stearoyl CoA desaturase- like protein
3k	CG105521-03	37	38	Stearoyl CoA desaturase- like protein
3l	CG105521-04	39	40	Stearoyl CoA desaturase- like protein
3m	CG105521-05	41	42	Stearoyl CoA desaturase- like protein
3n	CG105521-06	43	44	Stearoyl CoA desaturase- like protein
4a	CG107234-01	45	46	HYDROLASE like protein
4b	CG107234-03	47	48	HYDROLASE like protein
4c	CG107234-02	49	50	HYDROLASE like protein
5a	CG113144-01	51	52	CtBP like protein
5b	CG113144-02	53	54	CtBP like protein
5c	CG113144-03	55	56	CtBP like protein
6a	CG122634-01	57	58	Neuronal kinesin heavy chain protein
7a	CG125197-01	59	60	LYSOPHOSPHOLIPASE like protein
7b	CG125197-03	61	62	LYSOPHOSPHOLIPASE like protein
7c	CG125197-02	63	64	LYSOPHOSPHOLIPASE like protein
8a	CG125312-01	65	66	Myosin IF (Myosin IE) protein
9a	CG134439-01	67	68	Cation Efflux domain containing Protein
				like protein
10a	CG137109-01	69	70	phospholipid-transporting
				ATPase like protein
11a	CG137330-01	71	72	TGF-BETA Receptor Type I
				Precursor like protein
12a	CG137339-01	73	74	Epidermal Growth Factor Receptor
				Precursor like protein
12b	CG137339-02	75	76	Epidermal Growth Factor Receptor
				Precursor like protein
13a	CG138130-01	77	78	cGMP-stimulated 3′, 5′-cyclic
				nucleotide phosphodiesterase-like Proteins
14a	CG138372-01	79	80	Maleylacetoacetate Isomerase-
				like Proteins
14b	CG138372-02	81	82	Maleylacetoacetate Isomerase-
				like Proteins
14c	CG138372-01	83	84	Maleylacetoacetate Isomerase-
				like Proteins
14d	277582121	85	86	Maleylacetoacetate Isomerase-
				like Proteins
14e	CG138372-03	87	88	Maleylacetoacetate Isomerase-
				like Proteins
15a	CG138461-01	89	90	Intracellular Protein
				belonging to Nitroreductase
				family-like Proteins
16a	CG138529-01	91	92	Novel SA protein-like Proteins
17a	CG138563-01	93	94	Novel CHOLINE/ETHANOLAMINE KINASE-
				like protein
17b	CG138563-02	95	96	Novel CHOLINE/ETHANOLAMINE KINASE-
				like protein
18a	CG138848-01	97	98	Novel protein-tyrosine kinase ryk -
				Like-like Proteins
19a	CG139990-01	99	100	transferase HTFS-18 like protein
20a	CG140041-01	101	102	Pyridoxal-dependent decarboxylase
				like protein
21a	CG140061-01	103	104	IMP dehydrogenase like protein
22a	CG140335-01	105	106	urea transporter isoform UTA-3 like
				protein
23a	CG140355-01	107	108	PEPTIDYLPROLYL ISOMERASE
				A like protein
23b	CG140612-01	109	110	PEPTIDYLPROLYL ISOMERASE
				A like protein
24a	CG140612-02	111	112	ATP SYNTHASE B CHAIN, MITOCHONDRIAL
				like protein
25a	CG140696-01	113	114	AAA ATPase like protein
25b	CG140696-02	115	116	AAA ATPase like protein
25c	CG140696-03	117	118	AAA ATPase like protein
26a	CG140747-01	119	120	Dual specificity phosphatase
				like protein
27a	CG141137-01	121	122	long-chain acyl-coA thioesterase
				2 like protein
28a	CG141240-01	123	124	ATP synthase F chain, mitochondrial
				like protein
29a	CG141355-01	125	126	GTPASE RAB37 like protein
29b	CG141355-02	127	128	Novel GTPASE RAB37 -like Proteins
30a	CG142072-01	129	130	CATHEPSIN L PRECURSOR like protein
30b	CG142072-02	131	132	CATHEPSIN L PRECURSOR like protein
31a	CG142102-01	133	134	PEPTIDYLPROLYL ISOMERASE A
				(CYCLOPHILIN A) like protein
32a	CG57760-01	135	136	Prostaglandin-H2 D-isomerase
				precursor like protein
32b	CG57760-02	137	138	Prostaglandin-H2 D-isomerase
				precursor like protein
33a	CG59361-01	139	140	POTENTIAL PHOSPHOLIPID-TRANSPORTING
				ATPASE VA like protein
34a	CG59444-01	141	142	SA protein like protein
34b	CG59444-02	143	144	SA protein like protein
35a	CG59482-01	145	146	Trypsin I precursor like protein
35b	CG59482-02	147	148	Trypsin I precursor like protein
35c	CG59482-03	149	150	Trypsin I precursor like protein
36a	CG59522-01	151	152	Myosin I protein
36b	CG59522-02	153	154	Myosin I protein
37a	CG89709-01	155	156	Serine/threonine Protein kinase
				like protein
37b	CG89709-02	157	158	Serine/threonine Protein kinase
				like protein
37c	CG89709-03	159	160	novel ser/thr kinase protein
37d	CG89709-04	161	162	Serine/threonine Protein kinase
				like protein
37e	CG89709-01	163	164	Serine/threonine Protein kinase
				like protein
38a	CG90879-01	165	166	Protein kinase D2 like protein
39a	CG96334-01	167	168	DUAL-SPECIFICITY TYROSINE-
				PHOSPHORYLATION REGULATED
				KINASE 1A like protein
39b	CG96334-02	169	170	DUAL-SPECIFICITY TYROSINE-
				PHOSPHORYLATION REGULATED
				KINASE 1A like protein
40a	CG96714-01	171	172	UDP-galactose transporter related
				isozyme 1 protein
40b	212778987	173	174	UDP-galactose transporter related
				isozyme 1-like Proteins
40c	CG96714-02	175	176	UDP-galactose transporter related
				isozyme 1-like Proteins
40d	190235426	177	178	UDP-galactose transporter related
				isozyme 1-like Proteins
40e	CG96714-03	179	180	UDP-galactose transporter related
				isozyme 1-like Proteins
41a	CG97025-01	181	182	3-Hydroxy-3methylglutaryl coenzyme
				A synthase protein
41b	CG97025-01	183	184	Cytosolic HMG-CoA Synthase-like
				protein
41c	CG97025-01	185	186	HYDROXYMETHYLGLUTARYL-COA SYNTHASE,
				CYTOPLASMIC- like Proteins
41d	254869578	187	188	HYDROXYMETHYLGLUTARYL-COA SYNTHASE,
				CYTOPLASMIC- like Proteins
41e	CG97025-01	189	190	HYDROXYMETHYLGLUTARYL-COA SYNTHASE,
				CYTOPLASMIC- like Proteins
41f	253174237	191	192	HYDROXYMETHYLGLUTARYL-COA SYNTHASE,
				CYTOPLASMIC- like Proteins
41g	CG97025-01	193	194	HYDROXYMETHYLGLUTARYL-COA SYNTHASE,
				CYTOPLASMIC- like Proteins
41h	256420363	195	196	HYDROXYMETHYLGLUTARYL-COA SYNTHASE,
				CYTOPLASMIC- like Proteins
41i	CG97025-01	197	198	HYDROXYMETHYLGLUTARYL-COA SYNTHASE,
				CYTOPLASMIC- like Proteins
41j	255667064	199	200	HYDROXYMETHYLGLUTARYL-COA SYNTHASE,
				CYTOPLASMIC- like Proteins
41k	CG97025-01	201	202	Cytosolic HMG-CoA Synthase-
				like protein
41l	228832739	203	204	Cytosolic HMG-CoA Synthase-
				like protein
41m	CG97025-02	205	206	Cytosolic HMG-CoA Synthase-
				like protein
41n	CG97025-03	207	208	Cytosolic HMG-CoA Synthase-
				like protein
41o	CG97025-04	209	210	Cytosolic HMG-CoA Synthase-
				like protein
41p	CG97025-05	211	212	Cytosolic HMG-CoA Synthase-
				like protein
42a	CG97955-01	213	214	Carboxypeptidase A1 like protein
42b	CG97955-03	215	216	Carboxypeptidase A1 like protein
42c	308559628	217	218	Carboxypeptidase A1 like protein
42d	CG97955-02	219	220	Carboxypeptidase A1 like protein

[0027] Table A indicates the homology of NOVX polypeptides 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.

[0028] Pathologies, diseases, disorders and condition and the like that are associated with NOVX sequences include, but are not limited to: 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, metabolic disturbances associated with obesity, transplantation, adrenoleukodystrophy, congenital adrenal hyperplasia, prostate cancer, diabetes, metabolic disorders, neoplasm; adenocarcinoma, lymphoma, uterus cancer, fertility, hemophilia, hypercoagulation, idiopathic thrombocytopenic purpura, immunodeficiencies, graft versus host disease, AIDS, bronchial asthma, Crohn's disease; multiple sclerosis, treatment of Albright Hereditary Ostoeodystrophy, infectious disease, anorexia, cancer-associated cachexia, cancer, neurodegenerative disorders, Alzheimer's Disease, Parkinson's Disorder, immune disorders, hematopoietic disorders, and the various dyslipidemias,] the metabolic syndrome X and wasting disorders associated with chronic diseases and various cancers, as well as conditions such as transplantation and fertility.

[0029] 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.

[0030] 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.

[0031] 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.

[0032] 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. detection of a variety of cancers.

[0033] Additional utilities for NOVX nucleic acids and polypeptides according to the invention are disclosed herein.

[0034] NOVX Clones

[0035] 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.

[0036] 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.

[0037] 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) a biological defense weapon.

[0038] 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 110; (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 110, 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 110; (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 110 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).

[0039] 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 110; (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 110 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 110; (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 110, 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 110 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.

[0040] 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 110; (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 110 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 110; 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 110 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.

[0041] NOVX Nucleic Acids and Polypeptides

[0042] 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.

[0043] A 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, by way of nonlimiting example, as a result of one or more naturally occurring processing steps that may take place within the cell (e.g., 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, myristylation 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.

[0044] The term “probe”, as utilized herein, refers to nucleic acid sequences of variable length, preferably between at least about 10 nucleotides (nt), about 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-stranded or double-stranded and designed to have specificity in PCR, membrane-based hybridization technologies, or ELISA-like technologies.

[0045] The term “isolated” nucleic acid molecule, as used herein, is a nucleic acid that 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, or of chemical precursors or other chemicals.

[0046] A nucleic acid molecule of the invention, e.g., a nucleic acid molecule having the nucleotide sequence of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 110, or a complement of this 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 110, 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.)

[0047] A nucleic acid of the invention can be amplified using cDNA, mRNA or alternatively, genomic DNA, as a template with 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.

[0048] As used herein, the term “oligonucleotide” refers to a series of linked nucleotide residues. 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 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 of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 110, or a complement thereof. Oligonucleotides may be chemically synthesized and may also be used as probes.

[0049] 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 110, 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 a NOVX polypeptide). A nucleic acid molecule that is complementary to the nucleotide sequence of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 110, is one that is sufficiently complementary to the nucleotide sequence of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 110, that it can hydrogen bond with few or no mismatches to the nucleotide sequence shown in SEQ ID NO: 2n-1, wherein n is an integer between 1 and 110, thereby forming a stable duplex.

[0050] 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.

[0051] A “fragment” provided herein is defined as a sequence 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, and is 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.

[0052] 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.

[0053] A “derivative” is a nucleic acid sequence or amino acid sequence formed from the native compounds either directly, by modification or partial substitution. An “analog” is a nucleic acid sequence or amino acid sequence that has a structure similar to, but not identical to, the native compound, e.g. they differs from it in respect to certain components or side chains. Analogs may be synthetic or derived from a different evolutionary origin and may have a similar or opposite metabolic activity compared to wild type. A “homolog” is a nucleic acid sequence or amino acid sequence of a particular gene that is derived from different species.

[0054] Derivatives and analogs may be full length or other than full length. 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 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 include 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 a 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 110, as well as a polypeptide possessing NOVX biological activity. Various biological activities of the NOVX proteins are described below.

[0056] A NOVX polypeptide is encoded by the open reading frame (“ORF”) of a 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 bona fide 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 of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 110; or an anti-sense strand nucleotide sequence of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 110; or of a naturally occurring mutant of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 110.

[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 has a detectable label attached, e.g. the label 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 a NOVX protein, such as by measuring a level of a 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 a 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 of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 110, that encodes a polypeptide having a 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 of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 110, due to degeneracy of the genetic code and thus encode the same NOVX proteins as that encoded by the nucleotide sequences of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 110. In another embodiment, an isolated nucleic acid molecule of the invention has a nucleotide sequence encoding a protein having an amino acid sequence of SEQ ID NO: 2n, wherein n is an integer between 1 and 110.

[0062] In addition to the human NOVX nucleotide sequences of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 110, 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 a 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 a human SEQ ID NO: 2n-1, wherein n is an integer between 1 and 110, 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 110. 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 about 65% 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 defined ionic strength and pH. The Tm is the temperature (under defined ionic strength, pH and nucleic acid concentration) at which 50% of the probes complementary to the target sequence hybridize to the target sequence at equilibrium. Since the target sequences are generally present at excess, at Tm, 50% of the probes are occupied at equilibrium. Typically, stringent conditions will be those in which the salt concentration is less than about 1.0 M sodium ion, typically about 0.01 to 1.0 M sodium ion (or other salts) at 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 a sequence of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 110, 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 110, 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× Reinhardt's solution, 0.5% SDS and 100 mg/ml denatured salmon sperm DNA at 55° C., followed by one or more washes in 1×SSC, 0.1% SDS at 37° C. Other conditions of moderate stringency that may be used are well-known within the art. See, e.g., Ausubel, et al. (eds.), 1993, CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, NY, and Krieger, 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 of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 110, or fragments, analogs or derivatives thereof, under conditions of low stringency, is provided. A non-limiting example of low stringency hybridization onditions are hybridization in 35% formamide, 5×SSC, 50 mM Tris-HCl (pH 7.5), 5 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.2% BSA, 100 mg/ml denatured salmon sperm DNA, 10% (wt/vol) dextran sulfate at 40° C., followed by one or more washes in 2×SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1 % SDS at 50° C. Other conditions of low stringency that may be used are well known in the art (e.g., as employed for cross-species hybridizations). See, e.g., Ausubel, et al. (eds.), 1993, CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, NY, and Kriegler, 1990, GENE TRANSFER AND EXPRESSION, A LABORATORY MANUAL, Stockton Press, NY; Shilo and Weinberg, 1981. Proc Natl Acad Sci USA 78: 6789-6792.

[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 of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 110, thereby leading to changes in the amino acid sequences of the encoded NOVX protein, without altering the functional ability of that NOVX protein. For example, nucleotide substitutions leading to amino acid substitutions at “non-essential” amino acid residues can be made in the sequence of SEQ ID NO: 2n, wherein n is an integer between 1 and 110. 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-1, wherein n is an integer between 1 and 110, 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 40% homologous to the amino acid sequences of SEQ ID NO: 2n, wherein n is an integer between 1 and 110. 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 110; more preferably at least about 70% homologous to SEQ ID NO: 2n, wherein n is an integer between 1 and 110; still more preferably at least about 80% homologous to SEQ ID NO: 2n, wherein n is an integer between 1 and 110; even more preferably at least about 90% homologous to SEQ ID NO: 2n, wherein n is an integer between 1 and 110; and most preferably at least about 95% homologous to SEQ ID NO: 2n, wherein n is an integer between 1 and 110.

[0073] An isolated nucleic acid molecule encoding a NOVX protein homologous to the protein of SEQ ID NO: 2n, wherein n is an integer between 1 and 110, 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 110, such that one or more amino acid substitutions, additions or deletions are introduced into the encoded protein.

[0074] Mutations can be introduced any one of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 110, 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 a 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 a nucleic acid of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 110, 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 a 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] Interfering RNA

[0079] In one aspect of the invention, NOVX gene expression can be attenuated by RNA interference. One approach well-known in the art is short interfering RNA (siRNA) mediated gene silencing where expression products of a NOVX gene are targeted by specific double stranded NOVX derived siRNA nucleotide sequences that are complementary to at least a 19-25 nt long segment of the NOVX gene transcript, including the 5′ untranslated (UT) region, the ORF, or the 3′ UT region. See, e.g., PCT applications WO00/44895, WO99/32619, WO01/75164, WO01/92513, WO 01/29058, WO01/89304, WO02/16620, and WO02/29858, each incorporated by reference herein in their entirety. Targeted genes can be a NOVX gene, or an upstream or downstream modulator of the NOVX gene. Nonlimiting examples of upstream or downstream modulators of a NOVX gene include, e.g., a transcription factor that binds the NOVX gene promoter, a kinase or phosphatase that interacts with a NOVX polypeptide, and polypeptides involved in a NOVX regulatory pathway.

[0080] According to the methods of the present invention, NOVX gene expression is silenced using short interfering RNA. A NOVX polynucleotide according to the invention includes a siRNA polynucleotide. Such a NOVX siRNA can be obtained using a NOVX polynucleotide sequence, for example, by processing the NOVX ribopolynucleotide sequence in a cell-free system, such as but not limited to a Drosophila extract, or by transcription of recombinant double stranded NOVX RNA or by chemical synthesis of nucleotide sequences homologous to a NOVX sequence. See, e.g., Tuschl, Zamore, Lehmann, Bartel and Sharp (1999), Genes & Dev. 13: 3191-3197, incorporated herein by reference in its entirety. When synthesized, a typical 0.2 micromolar-scale RNA synthesis provides about 1 milligram of siRNA, which is sufficient for 1000 transfection experiments using a 24-well tissue culture plate format.

[0081] The most efficient silencing is generally observed with siRNA duplexes composed of a 21-nt sense strand and a 21-nt antisense strand, paired in a manner to have a 2-nt 3′ overhang. The sequence of the 2-nt 3′ overhang makes an additional small contribution to the specificity of siRNA target recognition. The contribution to specificity is localized to the unpaired nucleotide adjacent to the first paired bases. In one embodiment, the nucleotides in the 3′ overhang are ribonucleotides. In an alternative embodiment, the nucleotides in the 3′ overhang are deoxyribonucleotides. Using 2′-deoxyribonucleotides in the 3′ overhangs is as efficient as using ribonucleotides, but deoxyribonucleotides are often cheaper to synthesize and are most likely more nuclease resistant.

[0082] A contemplated recombinant expression vector of the invention comprises a NOVX DNA molecule cloned into an expression vector comprising operatively-linked regulatory sequences flanking the NOVX sequence in a manner that allows for expression (by transcription of the DNA molecule) of both strands. An RNA molecule that is antisense to NOVX mRNA is transcribed by a first promoter (e.g., a promoter sequence 3′ of the cloned DNA) and an RNA molecule that is the sense strand for the NOVX mRNA is transcribed by a second promoter (e.g., a promoter sequence 5′ of the cloned DNA). The sense and antisense strands may hybridize in vivo to generate siRNA constructs for silencing of the NOVX gene. Alternatively, two constructs can be utilized to create the sense and anti-sense strands of a siRNA construct. Finally, cloned DNA can encode a construct having secondary structure, wherein a single transcript has both the sense and complementary antisense sequences from the target gene or genes. In an example of this embodiment, a hairpin RNAi product is homologous to all or a portion of the target gene. In another example, a hairpin RNAi product is a siRNA. The regulatory sequences flanking the NOVX sequence may be identical or may be different, such that their expression may be modulated independently, or in a temporal or spatial manner.

[0083] In a specific embodiment, siRNAs are transcribed intracellularly by cloning the NOVX gene templates into a vector containing, e.g., a RNA pol III transcription unit from the smaller nuclear RNA (snRNA) U6 or the human RNase P RNA H1. One example of a vector system is the GeneSuppressor™ RNA Interference kit (commercially available from Imgenex). The U6 and H1 promoters are members of the type III class of Pol III promoters. The +1 nucleotide of the U6-like promoters is always guanosine, whereas the +1 for H1 promoters is adenosine. The termination signal for these promoters is defined by five consecutive thymidines. The transcript is typically cleaved after the second uridine. Cleavage at this position generates a 3′ UU overhang in the expressed siRNA, which is similar to the 3′ overhangs of synthetic siRNAs. Any sequence less than 400 nucleotides in length can be transcribed by these promoter, therefore they are ideally suited for the expression of around 21-nucleotide siRNAs in, e.g., an approximately 50-nucleotide RNA stem-loop transcript.

[0084] A siRNA vector appears to have an advantage over synthetic siRNAs where long term knock-down of expression is desired. Cells transfected with a siRNA expression vector would experience steady, long-term mRNA inhibition. In contrast, cells transfected with exogenous synthetic siRNAs typically recover from mRNA suppression within seven days or ten rounds of cell division. The long-term gene silencing ability of siRNA expression vectors may provide for applications in gene therapy.

[0085] In general, siRNAs are chopped from longer dsRNA by an ATP-dependent ribonuclease called DICER. DICER is a member of the RNase III family of double-stranded RNA-specific endonucleases. The siRNAs assemble with cellular proteins into an endonuclease complex. In vitro studies in Drosophila suggest that the siRNAs/protein complex (siRNP) is then transferred to a second enzyme complex, called an RNA-induced silencing complex (RISC), which contains an endoribonuclease that is distinct from DICER. RISC uses the sequence encoded by the antisense siRNA strand to find and destroy mRNAs of complementary sequence. The siRNA thus acts as a guide, restricting the ribonuclease to cleave only mRNAs complementary to one of the two siRNA strands.

[0086] A NOVX mRNA region to be targeted by siRNA is generally selected from a desired NOVX sequence beginning 50 to 100 nt downstream of the start codon. Alternatively, 5′ or 3′ UTRs and regions nearby the start codon can be used but are generally avoided, as these may be richer in regulatory protein binding sites. UTR-binding proteins and/or translation initiation complexes may interfere with binding of the siRNP or RISC endonuclease complex. An initial BLAST homology search for the selected siRNA sequence is done against an available nucleotide sequence library to ensure that only one gene is targeted. Specificity of target recognition by siRNA duplexes indicate that a single point mutation located in the paired region of an siRNA duplex is sufficient to abolish target mRNA degradation. See, Elbashir et al. 2001 EMBO J. 20(23):6877-88. Hence, consideration should be taken to accommodate SNPs, polymorphisms, allelic variants or species-specific variations when targeting a desired gene.

[0087] In one embodiment, a complete NOVX siRNA experiment includes the proper negative control. A negative control siRNA generally has the same nucleotide composition as the NOVX siRNA but lack significant sequence homology to the genome. Typically, one would scramble the nucleotide sequence of the NOVX siRNA and do a homology search to make sure it lacks homology to any other gene.

[0088] Two independent NOVX siRNA duplexes can be used to knock-down a target NOVX gene. This helps to control for specificity of the silencing effect. In addition, expression of two independent genes can be simultaneously knocked down by using equal concentrations of different NOVX siRNA duplexes, e.g., a NOVX siRNA and an siRNA for a regulator of a NOVX gene or polypeptide. Availability of siRNA-associating proteins is believed to be more limiting than target mRNA accessibility.

[0089] A targeted NOVX region is typically a sequence of two adenines (AA) and two thymidines (TT) divided by a spacer region of nineteen (N19) residues (e.g., AA(N19)TT). A desirable spacer region has a G/C-content of approximately 30% to 70%, and more preferably of about 50%. If the sequence AA(N19)TT is not present in the target sequence, an alternative target region would be AA(N21). The sequence of the NOVX sense siRNA corresponds to (N19)TT or N21, respectively. In the latter case, conversion of the 3′ end of the sense siRNA to TT can be performed if such a sequence does not naturally occur in the NOVX polynucleotide. The rationale for this sequence conversion is to generate a symmetric duplex with respect to the sequence composition of the sense and antisense 3′ overhangs. Symmetric 3′ overhangs may help to ensure that the siRNPs are formed with approximately equal ratios of sense and antisense target RNA-cleaving siRNPs. See, e.g., Elbashir, Lendeckel and Tuschl (2001). Genes & Dev. 15: 188-200, incorporated by reference herein in its entirely. The modification of the overhang of the sense sequence of the siRNA duplex is not expected to affect targeted mRNA recognition, as the antisense siRNA strand guides target recognition.

[0090] Alternatively, if the NOVX target mRNA does not contain a suitable AA(N21) sequence, one may search for the sequence NA(N21). Further, the sequence of the sense strand and antisense strand may still be synthesized as 5′ (N19)TT, as it is believed that the sequence of the 3′-most nucleotide of the antisense siRNA does not contribute to specificity. Unlike antisense or ribozyme technology, the secondary structure of the target mRNA does not appear to have a strong effect on silencing. See, Harborth, et al. (2001) J. Cell Science 114: 4557-4565, incorporated by reference in its entirety.

[0091] Transfection of NOVX siRNA duplexes can be achieved using standard nucleic acid transfection methods, for example, OLIGOFECTAMINE Reagent (commercially available from Invitrogen). An assay for NOVX gene silencing is generally performed approximately 2 days after transfection. No NOVX gene silencing has been observed in the absence of transfection reagent, allowing for a comparative analysis of the wild-type and silenced NOVX phenotypes. In a specific embodiment, for one well of a 24-well plate, approximately 0.84 μg of the siRNA duplex is generally sufficient. Cells are typically seeded the previous day, and are transfected at about 50% confluence. The choice of cell culture media and conditions are routine to those of skill in the art, and will vary with the choice of cell type. The efficiency of transfection may depend on the cell type, but also on the passage number and the confluency of the cells. The time and the manner of formation of siRNA-liposome complexes (e.g. inversion versus vortexing) are also critical. Low transfection efficiencies are the most frequent cause of unsuccessful NOVX silencing. The efficiency of transfection needs to be carefully examined for each new cell line to be used. Preferred cell are derived from a mammal, more preferably from a rodent such as a rat or mouse, and most preferably from a human. Where used for therapeutic treatment, the cells are preferentially autologous, although non-autologous cell sources are also contemplated as within the scope of the present invention.

[0092] For a control experiment, transfection of 0.84 μg single-stranded sense NOVX siRNA will have no effect on NOVX silencing, and 0.84 μg antisense siRNA has a weak silencing effect when compared to 0.84 μg of duplex siRNAs. Control experiments again allow for a comparative analysis of the wild-type and silenced NOVX phenotypes. To control for transfection efficiency, targeting of common proteins is typically performed, for, example targeting of lamin A/C or transfection of a CMV-driven EGFP-expression plasmid (e.g. commercially available from Clontech). In the above example, a determination of the fraction of lamin A/C knockdown in cells is determined the next day by such techniques as immunofluorescence, Western blot, Northern blot or other similar assays for protein expression or gene expression. Lamin A/C monoclonal antibodies may be obtained from Santa Cruz Biotechnology.

[0093] Depending on the abundance and the half life (or turnover) of the targeted NOVX polynucleotide in a cell, a knock-down phenotype may become apparent after 1 to 3 days, or even later. In cases where no NOVX knock-down phenotype is observed, depletion of the NOVX polynucleotide may be observed by immunofluorescence or Western blotting. If he NOVX polynucleotide is still abundant after 3 days, cells need to be split and transferred to a fresh 24-well plate for re-transfection. If no knock-down of the targeted protein is observed, it may be desirable to analyze whether the target mRNA (NOVX or a NOVX upstream or downstream gene) was effectively destroyed by the transfected siRNA duplex. Two days after transfection, total RNA is prepared, reverse transcribed using a target-specific primer, and PCR-amplified with a primer pair covering at least one exon-exon junction in order to control for amplification of pre-mRNAs. RT/PCR of a non-targeted mRNA is also needed as control. Effective depletion of the mRNA yet undetectable reduction of target protein may indicate that a large reservoir of stable NOVX protein may exist in the cell. Multiple transfection in sufficiently long intervals may be necessary until the target protein is finally depleted to a point where a phenotype may become apparent. If multiple transfection steps are required, cells are split 2 to 3 days after transfection. The cells may be transfected immediately after splitting.

[0094] An inventive therapeutic method of the invention contemplates administering a NOVX siRNA construct as therapy to compensate for increased or aberrant NOVX expression or activity. The NOVX ribopolynucleotide is obtained and processed into siRNA fragments, or a NOVX siRNA is synthesized, as described above. The NOVX siRNA is administered to cells or tissues using known nucleic acid transfection techniques, as described above. A NOVX siRNA specific for a NOVX gene will decrease or knockdown NOVX transcription products, which will lead to reduced NOVX polypeptide production, resulting in reduced NOVX polypeptide activity in the cells or tissues.

[0095] The present invention also encompasses a method of treating a disease or condition associated with the presence of a NOVX protein in an individual comprising administering to the individual an RNAi construct that targets the mRNA of the protein (the mRNA that encodes the protein) for degradation. A specific RNAi construct includes a siRNA or a double stranded gene transcript that is processed into siRNAs. Upon treatment, the target protein is not produced or is not produced to the extent it would be in the absence of the treatment.

[0096] Where the NOVX gene function is not correlated with a known phenotype, a control sample of cells or tissues from healthy individuals provides a reference standard for determining NOVX expression levels. Expression levels are detected using the assays described, e.g., RT-PCR, Northern blotting, Western blotting, ELISA, and the like. A subject sample of cells or tissues is taken from a mammal, preferably a human subject, suffering from a disease state. The NOVX ribopolynucleotide is used to produce siRNA constructs, that are specific for the NOVX gene product. These cells or tissues are treated by administering NOVX siRNA's to the cells or tissues by methods described for the transfection of nucleic acids into a cell or tissue, and a change in NOVX polypeptide or polynucleotide expression is observed in the subject sample relative to the control sample, using the assays described. This NOVX gene knockdown approach provides a rapid method for determination of a NOVX minus (NOVX−) phenotype in the treated subject sample. The NOVX− phenotype observed in the treated subject sample thus serves as a marker for monitoring the course of a disease state during treatment.

[0097] In specific embodiments, a NOVX siRNA is used in therapy. Methods for the generation and use of a NOVX siRNA are known to those skilled in the art. Example techniques are provided below.

[0098] Production of RNAs

[0099] Sense RNA (ssRNA) and antisense RNA (asRNA) of NOVX are produced using known methods such as transcription in RNA expression vectors. In the initial experiments, the sense and antisense RNA are about 500 bases in length each. The produced ssRNA and asRNA (0.5 μM) in 10 mM Tris-HCl (pH 7.5) with 20 mM NaCl were heated to 95° C. for 1 min then cooled and annealed at room temperature for 12 to 16 h. The RNAs are precipitated and resuspended in lysis buffer (below). To monitor annealing, RNAs are electrophoresed in a 2% agarose gel in TBE buffer and stained with ethidium bromide. See, e.g., Sambrook et al., Molecular Cloning. Cold Spring Harbor Laboratory Press, Plainview, N.Y. (1989).

[0100] Lysate Preparation

[0101] Untreated rabbit reticulocyte lysate (Ambion) are assembled according to the manufacturer's directions. dsRNA is incubated in the lysate at 30° C. for 10 min prior to the addition of mRNAs. Then NOVX mRNAs are added and the incubation continued for an additional 60 min. The molar ratio of double stranded RNA and mRNA is about 200:1. The NOVX mRNA is radiolabeled (using known techniques) and its stability is monitored by gel electrophoresis.

[0102] In a parallel experiment made with the same conditions, the double stranded RNA is internally radiolabeled with a 32P-ATP. Reactions are stopped by the addition of 2× proteinase K buffer and deproteinized as described previously (Tuschl et al., Genes Dev., 13:3191-3197 (1999)). Products are analyzed by electrophoresis in 15% or 18% polyacrylamide sequencing gels using appropriate RNA standards. By monitoring the gels for radioactivity, the natural production of 10 to 25 nt RNAs from the double stranded RNA can be determined.

[0103] The band of double stranded RNA, about 21-23 bps, is eluded. The efficacy of these 21-23 mers for suppressing NOVX transcription is assayed in vitro using the same rabbit reticulocyte assay described above using 50 nanomolar of double stranded 21-23 mer for each assay. The sequence of these 21-23 mers is then determined using standard nucleic acid sequencing techniques.

[0104] RNA Preparation

[0105] 21 nt RNAs, based on the sequence determined above, are chemically synthesized using Expedite RNA phosphoramidites and thymidine phosphoramidite (Proligo, Germany). Synthetic oligonucleotides are deprotected and gel-purified (Elbashir, Lendeckel, & Tuschl, Genes & Dev. 15, 188-200 (2001)), followed by Sep-Pak C18 cartridge (Waters, Milford, Mass., USA) purification (Tuschl, et al., Biochemistry, 32:11658-11668 (1993)).

[0106] These RNAs (20 μM) single strands are incubated in annealing buffer (100 mM potassium acetate, 30 mM HEPES-KOH at pH 7.4, 2 mM magnesium acetate) for 1 min at 90° C. followed by 1 h at 37° C.

[0107] Cell Culture

[0108] A cell culture known in the art to regularly express NOVX is propagated using standard conditions. 24 hours before transfection, at approx. 80% confluency, the cells are trypsinized and diluted 1:5 with fresh medium without antibiotics (1-3×105 cells/ml) and transferred to 24-well plates (500 ml/well). Transfection is performed using a commercially available lipofection kit and NOVX expression is monitored using standard techniques with positive and negative control. A positive control is cells that naturally express NOVX while a negative control is cells that do not express NOVX. Base-paired 21 and 22 nt siRNAs with overhanging 3′ ends mediate efficient sequence-specific mRNA degradation in lysates and in cell culture. Different concentrations of siRNAs are used. An efficient concentration for suppression in vitro in mammalian culture is between 25 nM to 100 nM final concentration. This indicates that siRNAs are effective at concentrations that are several orders of magnitude below the concentrations applied in conventional antisense or ribozyme gene targeting experiments.

[0109] The above method provides a way both for the deduction of NOVX siRNA sequence and the use of such siRNA for in vitro suppression. In vivo suppression may be performed using the same siRNA using well known in vivo transfection or gene therapy transfection techniques.

[0110] Antisense Nucleic Acids

[0111] 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 110, 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 a NOVX protein of SEQ ID NO: 2n, wherein n is an integer between 1 and 110, or antisense nucleic acids complementary to a NOVX nucleic acid sequence of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 110, are additionally provided.

[0112] In one embodiment, an antisense nucleic acid molecule is antisense to a “coding region” of the coding strand of a nucleotide sequence encoding a 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).

[0113] 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).

[0114] 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-carboxymethylaminomethyl-2-thiouridine, pseudouracil, 5-(carboxyhydroxylmethyl) uracil, 5-carboxymethylaminomethyluracil, dihydrouracil, beta-D-galactosylqueosine, inosine, N6-isopentenyladenine, 1-methylguanine, 2-thiouracil, 4-thiouracil, 1-methylinosine, 2,2-dimethylguanine, 2-methyladenine, 2-methylguanine, 5-methoxyuracil, 3-methylcytosine, 5-methylcytosine, N6-adenine, 7-methylguanine, queosine, 2-thiocytosine, 5-methylaminomethyluracil, 5-methoxyaminomethyl-2-thiouracil, 2-methylthio-N6-isopentenyladenine, beta-D-mannosylqueosine, 5-methyl-2-thiouracil, 5′-methoxycarboxymethyluracil, uracil-5-oxyacetic acid (v), wybutoxosine, 5-methyluracil, uracil-5-oxyacetic acid methylester, uracil-5-oxyacetic acid (v), 5-methyl-2-thiouracil, 3-(3-amino-3-N-2-carboxypropyl) uracil, (acp3)w, and 2,6-diaminopurine. Alternatively, the antisense nucleic acid can be produced biologically using an expression vector into which a nucleic acid has been subcloned in an antisense orientation (i.e., RNA transcribed from the inserted nucleic acid will be of an antisense orientation to a target nucleic acid of interest, described further in the following subsection).

[0115] 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 a 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.

[0116] 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.

[0117] Ribozymes and PNA Moieties

[0118] 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.

[0119] 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 a NOVX-encoding nucleic acid can be designed based upon the nucleotide sequence of a NOVX cDNA disclosed herein (i.e., SEQ ID NO: 2n-1, wherein n is an integer between 1 and 110). 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 a 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.

[0120] 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.

[0121] 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 nucleotide bases 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 oligomer 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.

[0122] 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).

[0123] 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 nucleotide bases, 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.

[0124] In other embodiments, the oligonucleotide may include other appended groups such as peptides (e.g., for targeting host cell receptors in vivo), or agents facilitating transport across the cell membrane (see, e.g., Letsinger, et al., 1989. Proc. Natl. Acad. Sci. U.S.A. 86: 6553-6556; Lemaitre, et al., 1987. Proc. Natl. Acad. Sci. 84: 648-652; PCT Publication No. WO88/09810) or the blood-brain barrier (see, e.g., PCT Publication No. WO 89/10134). In addition, oligonucleotides can be modified with hybridization triggered cleavage agents (see, e.g., Krol, et al., 1988. BioTechniques 6:958-976) or intercalating agents (see, e.g., Zon, 1988. Pharm. Res. 5: 539-549). To this end, the oligonucleotide may be conjugated to another molecule, e.g., a peptide, a hybridization triggered cross-linking agent, a transport agent, a hybridization-triggered cleavage agent, and the like.

[0125] NOVX Polypeptides

[0126] A polypeptide according to the invention includes a polypeptide including the amino acid sequence of NOVX polypeptides whose sequences are provided in any one of SEQ ID NO: 2n, wherein n is an integer between 1 and 110. The invention also includes a mutant or variant protein any of whose residues may be changed from the corresponding residues shown in any one of SEQ ID NO: 2n, wherein n is an integer between 1 and 110, while still encoding a protein that maintains its NOVX activities and physiological functions, or a functional fragment thereof.

[0127] In general, a 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.

[0128] 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, a NOVX protein or polypeptide can be synthesized chemically using standard peptide synthesis techniques.

[0129] 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.

[0130] 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.

[0131] 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 of SEQ ID NO: 2n, wherein n is an integer between 1 and 110) that include fewer amino acids than the full-length NOVX proteins, and exhibit at least one activity of a 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 a NOVX protein can be a polypeptide which is, for example, 10, 25, 50, 100 or more amino acid residues in length.

[0132] 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.

[0133] In an embodiment, the NOVX protein has an amino acid sequence of SEQ ID NO: 2n, wherein n is an integer between 1 and 110. In other embodiments, the NOVX protein is substantially homologous to SEQ ID NO: 2n, wherein n is an integer between 1 and 110, and retains the functional activity of the protein of SEQ ID NO: 2n, wherein n is an integer between 1 and 110, 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 of SEQ ID NO: 2n, wherein n is an integer between 1 and 110, and retains the functional activity of the NOVX proteins of SEQ ID NO: 2n, wherein n is an integer between 1 and 110.

[0134] Determining Homology Between Two or More Sequences

[0135] 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”).

[0136] 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 of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 110.

[0137] 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.

[0138] Chimeric and Fusion Proteins

[0139] The invention also provides NOVX chimeric or fusion proteins. As used herein, a NOVX “chimeric protein” or “fusion protein” comprises a NOVX polypeptide operatively-linked to a non-NOVX polypeptide. An “NOVX polypeptide” refers to a polypeptide having an amino acid sequence corresponding to a NOVX protein of SEQ ID NO: 2n, wherein n is an integer between 1 and 110, 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 a NOVX fusion protein the NOVX polypeptide can correspond to all or a portion of a NOVX protein. In one embodiment, a NOVX fusion protein comprises at least one biologically-active portion of a NOVX protein. In another embodiment, a NOVX fusion protein comprises at least two biologically-active portions of a NOVX protein. In yet another embodiment, a NOVX fusion protein comprises at least three biologically-active portions of a 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.

[0140] 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.

[0141] In another embodiment, the fusion protein is a 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.

[0142] In yet another embodiment, the fusion protein is a 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 a NOVX ligand and a 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 a 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 a NOVX ligand.

[0143] A 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, PCP 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). A 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.

[0144] NOVX Agonists and Antagonists

[0145] 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.

[0146] 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.

[0147] Polypeptide Libraries

[0148] 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 a NOVX protein. In one embodiment, a library of coding sequence fragments can be generated by treating a double stranded PCR fragment of a 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.

[0149] 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.

[0150] Anti-NOVX Antibodies

[0151] 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, antibody molecules obtained from humans relates to any of the classes IgG, IgM, IgA, IgE and IgD, which differ from one another by the nature of the heavy chain present in the molecule. Certain classes have subclasses as well, such as IgG1, IgG2, and others. Furthermore, in humans, the light chain may be a kappa chain or a lambda chain. Reference herein to antibodies includes a reference to all such classes, subclasses and types of human antibody species.

[0152] An isolated protein of the invention intended to serve as an antigen, or a portion or fragment thereof, can be used as an immunogen to generate antibodies that immunospecifically bind the antigen, using standard techniques for polyclonal and monoclonal antibody preparation. The full-length protein can be used or, alternatively, the invention provides antigenic peptide fragments of the antigen for use as immunogens. An antigenic peptide fragment comprises at least 6 amino acid residues of the amino acid sequence of the full length protein, such as an amino acid sequence of SEQ ID NO: 2n, wherein n is an integer between 1 and 110, 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.

[0153] In certain embodiments of the invention, at least one epitope encompassed by the antigenic peptide is a region of NOVX that is located on the surface of the protein, e.g., a hydrophilic region. A hydrophobicity analysis of the human NOVX protein sequence will indicate which regions of a NOVX polypeptide are particularly hydrophilic and, therefore, are likely to encode surface residues useful for targeting antibody production. As a means for targeting antibody production, hydropathy plots showing regions of hydrophilicity and hydrophobicity may be generated by any method well known in the art, including, for example, the Kyte Doolittle or the Hopp Woods methods, either with or without Fourier transformation. See, e.g., Hopp and Woods, 1981, Proc. Nat. Acad. Sci. USA 78: 3824-3828; Kyte and Doolittle 1982, J. Mol. Biol. 157: 105-142, each incorporated herein by reference in their entirety. Antibodies that are specific for one or more domains within an antigenic protein, or derivatives, fragments, analogs or homologs thereof, are also provided herein.

[0154] The term “epitope” includes any protein determinant capable of specific binding to an immunoglobulin or T-cell receptor. Epitopic determinants usually consist of chemically active surface groupings of molecules such as amino acids or sugar side chains and usually have specific three dimensional structural characteristics, as well as specific charge characteristics. A NOVX polypeptide or a fragment thereof comprises at least one antigenic epitope. An anti-NOVX antibody of the present invention is said to specifically bind to antigen NOVX when the equilibrium binding constant (KD) is ≦1 μM, preferably ≦100 nM, more preferably ≦10 nM, and most preferably ≦100 pM to about 1 pM, as measured by assays such as radioligand binding assays or similar assays known to those skilled in the art.

[0155] 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.

[0156] Various procedures known within the art may be used for the production of polyclonal or monoclonal antibodies directed against a protein of the invention, or against derivatives, fragments, analogs homologs or orthologs thereof (see, for example, Antibodies: A Laboratory Manual, Harlow E, and Lane D, 1988, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., incorporated herein by reference). Some of these antibodies are discussed below.

[0157] Polyclonal Antibodies

[0158] 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).

[0159] 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).

[0160] Monoclonal Antibodies

[0161] 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.

[0162] 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.

[0163] 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.

[0164] Preferred immortalized cell lines are those that fuse efficiently, support stable high level expression of antibody by the selected antibody-producing cells, and are sensitive to a medium such as HAT medium. More preferred immortalized cell lines are murine myeloma lines, which can be obtained, for instance, from the Salk Institute Cell Distribution Center, San Diego, Calif. and the American Type Culture Collection, Manassas, Va. Human myeloma and mouse-human heteromyeloma cell lines also have been described for the production of human monoclonal antibodies (Kozbor, J. Immunol., 133:3001 (1984); Brodeur et al., Monoclonal Antibody Production Techniques and Applications, Marcel Dekker, Inc., New York, (1987) pp. 51-63).

[0165] The culture medium in which the hybridoma cells are cultured can then be assayed for the presence of monoclonal antibodies directed against the antigen. Preferably, the binding specificity of monoclonal antibodies produced by the hybridoma cells is determined by immunoprecipitation or by an in vitro binding assay, such as radioimmunoassay (RIA) or enzyme-linked immunoabsorbent assay (ELISA). Such techniques and assays are known in the art. The binding affinity of the monoclonal antibody can, for example, be determined by the Scatchard analysis of Munson and Pollard, Anal. Biochem., 107:220 (1980). It is an objective, especially important in therapeutic applications of monoclonal antibodies, to identify antibodies having a high degree of specificity and a high binding affinity for the target antigen.

[0166] After the desired hybridoma cells are identified, the clones can be subcloned by limiting dilution procedures and grown by standard methods (Goding,1986). Suitable culture media for this purpose include, for example, Dulbecco's Modified Eagle's Medium and RPMI-1640 medium. Alternatively, the hybridoma cells can be grown in vivo as ascites in a mammal.

[0167] 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. I 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.

[0168] Humanized Antibodies

[0169] 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. Patent 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)).

[0170] Human Antibodies

[0171] Fully human antibodies essentially relate to antibody molecules in which the entire sequence of both the light chain and the heavy chain, including the CDRs, arise from human genes. Such antibodies are termed “human antibodies”, or “fully human antibodies” herein. Human monoclonal antibodies can be prepared by the trioma technique; the human B-cell hybridoma technique (see Kozbor, et al., 1983 Immunol Today 4: 72) and the EBV hybridoma technique to produce human monoclonal antibodies (see Cole, et al., 1985 In: MONOCLONAL ANTIBODIES AND CANCER THERAPY, Alan R. Liss, Inc., pp. 77-96). Human monoclonal antibodies may be utilized in the practice of the present invention and may be produced by using human hybridomas (see Cote, et al., 1983. Proc Natl Acad Sci USA 80: 2026-2030) or by transforming human B-cells with Epstein Barr Virus in vitro (see Cole, et al., 1985 In: MONOCLONAL ANMBODIES AND CANCER THERAPY, Alan R. Liss, Inc., pp. 77-96).

[0172] 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)).

[0173] 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.

[0174] 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.

[0175] 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.

[0176] 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.

[0177] Fab Fragments and Single Chain Antibodies

[0178] 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.

[0179] Bispecific Antibodies

[0180] 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.

[0181] Methods for making bispecific antibodies are known in the art. Traditionally, the recombinant production of bispecific antibodies is based on the co-expression of two immunoglobulin heavy-chain/light-chain pairs, where the two heavy chains have different specificities (Milstein and Cuello, Nature, 305:537-539 (1983)). Because of the random assortment of immunoglobulin heavy and light chains, these hybridomas (quadromas) produce a potential mixture of ten different antibody molecules, of which only one has the correct bispecific structure. The purification of the correct molecule is usually accomplished by affinity chromatography steps. Similar procedures are disclosed in WO 93/08829, published May 13, 1993, and in Traunecker et al., EMBO J., 10:3655-3659 (1991).

[0182] Antibody variable domains with the desired binding specificities (antibody-antigen combining sites) can be fused to immunoglobulin constant domain sequences. The fusion preferably is with an immunoglobulin heavy-chain constant domain, comprising at least part of the hinge, CH2, and CH3 regions. It is preferred to have the first heavy-chain constant region (CH1) containing the site necessary for light-chain binding present in at least one of the fusions. DNAs encoding the immunoglobulin heavy-chain fusions and, if desired, the immunoglobulin light chain, are inserted into separate expression vectors, and are co-transfected into a suitable host organism. For further details of generating bispecific antibodies see, for example, Suresh et al., Methods in Enzymology, 121:210 (1986).

[0183] 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.

[0184] 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 thioritrobenzoate (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.

[0185] 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.

[0186] Various techniques for making and isolating bispecific antibody fragments directly from recombinant cell culture have also been described. For example, bispecific antibodies have been produced using leucine zippers. Kostelny et al., J. Immunol. 148(5):1547-1553 (1992). The leucine zipper peptides from the Fos and Jun proteins were linked to the Fab′ portions of two different antibodies by gene fusion. The antibody homodimers were reduced at the hinge region to form monomers and then re-oxidized to form the antibody heterodimers. This method can also be utilized for the production of antibody homodimers. The “diabody” technology described by Hollinger et al., Proc. Natl. Acad. Sci. USA 90:6444-6448 (1993) has provided an alternative mechanism for making bispecific antibody fragments. The fragments comprise a heavy-chain variable domain (VH) connected to a light-chain variable domain (VL) by a linker which is too short to allow pairing between the two domains on the same chain. Accordingly, the VH and VL domains of one fragment are forced to pair with the complementary VL and VH domains of another fragment, thereby forming two antigen-binding sites. Another strategy for making bispecific antibody fragments by the use of single-chain Fv (sFv) dimers has also been reported. See, Gruber et al., J. Immunol. 152:5368 (1994).

[0187] Antibodies with more than two valencies are contemplated. For example, trispecific antibodies can be prepared. Tutt et al., J. Immunol. 147:60 (1991).

[0188] 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 (FcdγR), 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).

[0189] Heteroconjugate Antibodies

[0190] 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.

[0191] Effector Function Engineering

[0192] 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).

[0193] Immunoconjugates

[0194] 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).

[0195] 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 212 Bi, 131I, 131In, 90Y, and 186Re.

[0196] 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.

[0197] 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.

[0198] Immunoliposomes

[0199] The antibodies disclosed herein can also be formulated as immunoliposomes. Liposomes containing the antibody are prepared by methods known in the art, such as described in Epstein et al., Proc. Natl. Acad. Sci. USA, 82: 3688 (1985); Hwang et al., Proc. Natl Acad. Sci. USA, 77: 4030 (1980); and U.S. Pat. Nos. 4,485,045 and 4,544,545. Liposomes with enhanced circulation time are disclosed in U.S. Pat. No. 5,013,556.

[0200] Particularly useful liposomes can be generated by the reverse-phase evaporation method with a lipid composition comprising phosphatidylcholine, cholesterol, and PEG-derivatized phosphatidylethanolamine (PEG-PE). Liposomes are extruded through filters of defined pore size to yield liposomes with the desired diameter. Fab′ fragments of the antibody of the present invention can be conjugated to the liposomes as described in Martin et al., J. Biol. Chem., 257: 286-288 (1982) via a disulfide-interchange reaction. A chemotherapeutic agent (such as Doxorubicin) is optionally contained within the liposome. See Gabizon et al., J. National Cancer Inst., 81(19): 1484 (1989).

[0201] Diagnostic Applications of Antibodies Directed Against the Proteins of the Invention

[0202] 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.

[0203] Antibodies directed against a NOVX protein of the invention may be used in methods known within the art relating to the localization and/or quantitation of a 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 specific to a NOVX protein, or derivative, fragment, analog or homolog thereof, that contain the antibody derived antigen binding domain, are utilized as pharmacologically active compounds (referred to hereinafter as “Therapeutics”).

[0204] An antibody specific for a NOVX protein of the invention (e.g., a monoclonal antibody or a polyclonal antibody) can be used to isolate a NOVX polypeptide by standard techniques, such as immunoaffinity, chromatography or immunoprecipitation. An antibody to a NOVX polypeptide can facilitate the purification of a natural NOVX antigen from cells, or of a recombinantly produced NOVX antigen expressed in host cells. Moreover, such an anti-NOVX antibody can be used to detect the antigenic NOVX protein (e.g., in a cellular lysate or cell supernatant) in order to evaluate the abundance and pattern of expression of the antigenic NOVX protein. Antibodies directed against a NOVX protein can be used diagnostically to monitor protein levels in tissue as part of a clinical testing procedure, e.g., to, for example, determine the efficacy of a given treatment regimen. Detection can be facilitated by coupling (i.e., physically linking) the antibody to a detectable substance. Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, β-galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include streptavidin/biotin and avidin/biotin; examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin, and examples of suitable radioactive material include 125I, 131I, 35S or 3H.

[0205] Antibody Therapeutics

[0206] Antibodies of the invention, including polyclonal, monoclonal, humanized and fully human antibodies, may used as therapeutic agents. Such agents will generally be employed to treat or prevent a disease or pathology in a subject. An antibody preparation, preferably one having high specificity and high affinity for its target antigen, is administered to the subject and will generally have an effect due to its binding with the target. Such an effect may be one of two kinds, depending on the specific nature of the interaction between the given antibody molecule and the target antigen in question. In the first instance, administration of the antibody may abrogate or inhibit the binding of the target with an endogenous ligand to which it naturally binds. In this case, the antibody binds to the target and masks a binding site of the naturally occurring ligand, wherein the ligand serves as an effector molecule. Thus the receptor mediates a signal transduction pathway for which ligand is responsible.

[0207] Alternatively, the effect may be one in which the antibody elicits a physiological result by virtue of binding to an effector binding site on the target molecule. In this case the target, a receptor having an endogenous ligand which may be absent or defective in the disease or pathology, binds the antibody as a surrogate effector ligand, initiating a receptor-based signal transduction event by the receptor.

[0208] A therapeutically effective amount of an antibody of the invention relates generally to the amount needed to achieve a therapeutic objective. As noted above, this may be a binding interaction between the antibody and its target antigen that, in certain cases, interferes with the functioning of the target, and in other cases, promotes a physiological response. The amount required to be administered will furthermore depend on the binding affinity of the antibody for its specific antigen, and will also depend on the rate at which an administered antibody is depleted from the free volume other subject to which it is administered. Common ranges for therapeutically effective dosing of an antibody or antibody fragment of the invention may be, by way of nonlimiting example, from about 0.1 mg/kg body weight to about 50 mg/kg body weight. Common dosing frequencies may range, for example, from twice daily to once a week.

[0209] Pharmaceutical Compositions of Antibodies

[0210] Antibodies specifically binding a protein of the invention, as well as other molecules identified by the screening assays disclosed herein, can be administered for the treatment of various disorders in the form of pharmaceutical compositions. Principles and considerations involved in preparing such compositions, as well as guidance in the choice of components are provided, for example, in Remington : The Science And Practice Of Pharmacy 19th ed. (Alfonso R. Gennaro, et al., editors) Mack Pub. Co., Easton, Pa.: 1995; Drug Absorption Enhancement: Concepts, Possibilities, Limitations, And Trends, Harwood Academic Publishers, Langhorne, Pa., 1994; and Peptide And Protein Drug Delivery (Advances In Parenteral Sciences, Vol. 4), 1991, M. Dekker, N.Y.

[0211] If the antigenic protein is intracellular and whole antibodies are used as inhibitors, internalizing antibodies are preferred. However, liposomes can also be used to deliver the antibody, or an antibody fragment, into cells. Where antibody fragments are used, the smallest inhibitory fragment that specifically binds to the binding domain of the target protein is preferred. For example, based upon the variable-region sequences of an antibody, peptide molecules can be designed that retain the ability to bind the target protein sequence. Such peptides can be synthesized chemically and/or produced by recombinant DNA technology. See, e.g., Marasco et al., Proc. Natl. Acad. Sci. USA, 90: 7889-7893 (1993). The formulation herein can also contain more than one active compound as necessary for the particular indication being treated, preferably those with complementary activities that do not adversely affect each other. Alternatively, or in addition, the composition can comprise an agent that enhances its function, such as, for example, a cytotoxic agent, cytokine, chemotherapeutic agent, or growth-inhibitory agent. Such molecules are suitably present in combination in amounts that are effective for the purpose intended.

[0212] The active ingredients can also be entrapped in microcapsules prepared, for example, by coacervation techniques or by interfacial polymerization, for example, hydroxymethylcellulose or gelatin-microcapsules and poly-(methylmethacrylate) microcapsules, respectively, in colloidal drug delivery systems (for example, liposomes, albumin microspheres, microemulsions, nano-particles, and nanocapsules) or in macroemulsions.

[0213] The formulations to be used for in vivo administration must be sterile. This is readily accomplished by filtration through sterile filtration membranes.

[0214] Sustained-release preparations can be prepared. Suitable examples of sustained-release preparations include semipermeable matrices of solid hydrophobic polymers containing the antibody, which matrices are in the form of shaped articles, e.g., films, or microcapsules. Examples of sustained-release matrices include polyesters, hydrogels (for example, poly(2-hydroxyethyl-methacrylate), or poly(vinylalcohol)), polylactides (U.S. Pat. No. 3,773,919), copolymers of L-glutamic acid and γ ethyl-L-glutamate, non-degradable ethylene-vinyl acetate, degradable lactic acid-glycolic acid copolymers such as the LUPRON DEPOT™ (injectable microspheres composed of lactic acid-glycolic acid copolymer and leuprolide acetate), and poly-D-(−)-3-hydroxybutyric acid. While polymers such as ethylene-vinyl acetate and lactic acid-glycolic acid enable release of molecules for over 100 days, certain hydrogels release proteins for shorter time periods.

[0215] ELISA Assay

[0216] An agent for detecting an analyte protein is an antibody capable of binding to an analyte protein, preferably an antibody with a detectable label. Antibodies can be polyclonal, or more preferably, monoclonal. An intact antibody, or a fragment thereof (e.g., Fab or F(ab)2) can be used. The term “labeled”, with regard to the probe or antibody, is intended to encompass direct labeling of the probe or antibody by coupling (i.e., physically linking) a detectable substance to the probe or antibody, as well as indirect labeling of the probe or antibody by reactivity with another reagent that is directly labeled. Examples of indirect labeling include detection of a primary antibody using a fluorescently-labeled secondary antibody and end-labeling of a DNA probe with biotin such that it can be detected with fluorescently-labeled streptavidin. The term “biological sample” is intended to include tissues, cells and biological fluids isolated from a subject, as well as tissues, cells and fluids present within a subject. Included within the usage of the term “biological sample”, therefore, is blood and a fraction or component of blood including blood serum, blood plasma, or lymph. That is, the detection method of the invention can be used to detect an analyte mRNA, protein, or genomic DNA in a biological sample in vitro as well as in vivo. For example, in vitro techniques for detection of an analyte mRNA include Northern hybridizations and in situ hybridizations. In vitro techniques for detection of an analyte protein include enzyme linked immunosorbent assays (ELISAs), Western blots, immunoprecipitations, and immunofluorescence. In vitro techniques for detection of an analyte genomic DNA include Southern hybridizations. Procedures for conducting immunoassays are described, for example in “ELISA: Theory and Practice: Methods in Molecular Biology”, Vol. 42, J. R. Crowther (Ed.) Human Press, Totowa, N.J., 1995; “Immunoassay”, E. Diamandis and T. Christopoulus, Academic Press, Inc., San Diego, Calif., 1996; and “Practice and Thory of Enzyme Immunoassays”, P. Tijssen, Elsevier Science Publishers, Amsterdam, 1985. Furthermore, in vivo techniques for detection of an analyte protein include introducing into a subject a labeled anti-an analyte protein antibody. For example, the antibody can be labeled with a radioactive marker whose presence and location in a subject can be detected by standard imaging techniques.

[0217] NOVX Recombinant Expression Vectors and Host Cells

[0218] Another aspect of the invention pertains to vectors, preferably expression vectors, containing a nucleic acid encoding a 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.

[0219] The recombinant expression vectors of the invention comprise a nucleic acid of the invention in a form suitable for expression of the nucleic acid in a host cell, which means that the recombinant expression vectors include one or more regulatory sequences, selected on the basis of the host cells to be used for expression, that is operatively-linked to the nucleic acid sequence to be expressed. Within a recombinant expression vector, “operably-linked” is intended to mean that the nucleotide sequence of interest is linked to the regulatory sequence(s) in a manner that allows for expression of the nucleotide sequence (e.g., in an in vitro transcription/translation system or in a host cell when the vector is introduced into the host cell).

[0220] 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.).

[0221] 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 n. 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.

[0222] 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.

[0223] Examples of suitable inducible non-fusion E. coli expression vectors include pTrc (Amrann et al., (1988) Gene 69:301-315) and pET 11d (Studier et al., GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990) 60-89).

[0224] 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.

[0225] 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 (Kurjan and Herskowitz, 1982. Cell 30: 933-943), pJRY88 (Schultz et al., 1987. Gene 54: 113-123), pYES2 (Invitrogen Corporation, San Diego, Calif.), and picZ (InVitrogen Corp, San Diego, Calif.).

[0226] 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).

[0227] 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.

[0228] 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 (Banerji, 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).

[0229] 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.

[0230] 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.

[0231] 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.

[0232] 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.

[0233] 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).

[0234] 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.

[0235] Transgenic NOVX Animals

[0236] 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.

[0237] 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, i.e., any one of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 110, 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.

[0238] To create a homologous recombinant animal, a vector is prepared which contains at least a portion of a 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 any one of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 110), 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 110, 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).

[0239] 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.

[0240] 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.

[0241] 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.

[0242] 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.

[0243] Pharmaceutical Compositions 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.

[0244] A pharmaceutical composition of the invention is formulated to be compatible with its intended route of administration. Examples of routes of administration include parenteral, e.g., intravenous, intradermal, subcutaneous, oral (e.g., inhalation), transdermal (i.e., topical), transmucosal, and rectal administration. Solutions or suspensions used for parenteral, intradermal, or subcutaneous application can include the following components: a sterile diluent such as water for injection, saline solution, fixed oils, polyethylene glycols, glycerine, propylene glycol or other synthetic solvents; antibacterial agents such as benzyl alcohol or methyl parabens; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as ethylenediaminetetraacetic acid (EDTA); buffers such as acetates, citrates or phosphates, and agents for the adjustment of tonicity such as sodium chloride or dextrose. The pH can be adjusted with acids or bases, such as hydrochloric acid or sodium hydroxide. The parenteral preparation can be enclosed in ampoules, disposable syringes or multiple dose vials made of glass or plastic.

[0245] 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.

[0246] Sterile injectable solutions can be prepared by incorporating the active compound (e.g., a 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.

[0247] 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.

[0248] 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.

[0249] 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.

[0250] 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.

[0251] 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.

[0252] 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.

[0253] 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.

[0254] The pharmaceutical compositions can be included in a container, pack, or dispenser together with instructions for administration.

[0255] Screening and Detection Methods

[0256] 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 a 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.

[0257] The invention further pertains to novel agents identified by the screening assays described herein and uses thereof for treatments as described, supra.

[0258] Screening Assays

[0259] 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.

[0260] 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 a NOVX protein or polypeptide or biologically-active portion thereof. The test compounds of the invention can be obtained using any of the numerous approaches in combinatorial library methods known in the art, including: biological libraries; spatially addressable parallel solid phase or solution phase libraries; synthetic library methods requiring deconvolution; the “one-bead one-compound” library method; and synthetic library methods using affinity chromatography selection. The biological library approach is limited to peptide libraries, while the other four approaches are applicable to peptide, non-peptide oligomer or small molecule libraries of compounds. See, e.g., Lam, 1997. Anticancer Drug Design 12: 145.

[0261] 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.

[0262] 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.

[0263] Libraries of compounds may be presented in solution (e.g., Houghten, 1992. Biotechniques 13: 412-421), or on beads (Lam, 1991. Nature 354: 82-84), on chips (Fodor, 1993. Nature 364: 555-556), bacteria (Ladner, U.S. Pat. No. 5,223,409), spores (Ladner, U.S. Pat. No. 5,233,409), plasmids (Cull, et al., 1992. Proc. Natl. Acad. Sci. USA 89: 1865-1869) or on phage (Scott and Smith, 1990. Science 249: 386-390; Devlin, 1990. Science 249: 404-406; Cwirla, et al., 1990. Proc. Natl. Acad. Sci. U.S.A. 87: 6378-6382; Felici, 1991. J. Mol. Biol. 222: 301-310; Ladner, U.S. Pat. No. 5,233,409.).

[0264] 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 a 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 a NOVX protein, wherein determining the ability of the test compound to interact with a 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.

[0265] 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 a NOVX target molecule. As used herein, a “target molecule” is a molecule with which a NOVX protein binds or interacts in nature, for example, a molecule on the surface of a cell which expresses a 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. A NOVX target molecule can be a non-NOVX molecule or a NOVX protein or polypeptide of the invention. In one embodiment, a 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.

[0266] Determining the ability of the NOVX protein to bind to or interact with a 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 a 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 a 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.

[0267] In yet another embodiment, an assay of the invention is a cell-free assay comprising contacting a 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 a NOVX protein, wherein determining the ability of the test compound to interact with a 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.

[0268] 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 a 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 a NOVX target molecule. For example, the catalytic/enzymatic activity of the target molecule on an appropriate substrate can be determined as described, supra.

[0269] 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 a NOVX protein, wherein determining the ability of the test compound to interact with a NOVX protein comprises determining the ability of the NOVX protein to preferentially bind to or modulate the activity of a NOVX target molecule.

[0270] The cell-free assays of the invention are amenable to use of both the soluble form or the membrane-bound form of NOVX protein. In the case of cell-free assays comprising the membrane-bound form of NOVX protein, it may be desirable to utilize a solubilizing agent such that the membrane-bound form of NOVX protein is maintained in solution. Examples of such solubilizing agents include non-ionic detergents such as n-octylglucoside, n-dodecylglucoside, n-dodecylmaltoside, octanoyl-N-methylglucamide, decanoyl-N-methylglucamide, Triton® X-100, Triton® X-114, Thesit®, Isotridecypoly(ethylene glycol ether)n, N-dodecyl-N,N-dimethyl-3-ammonio-1-propane sulfonate, 3-(3-cholamidopropyl) dimethylamminiol-1-propane sulfonate (CHAPS), or 3-(3-cholamidopropyl)dimethylamminiol-2-hydroxy-1-propane sulfonate (CHAPSO).

[0271] 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.

[0272] 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.

[0273] In another embodiment, modulators of NOVX protein expression are identified in a method wherein a cell is contacted with a candidate compound and the expression of NOVX mRNA or protein in the cell is determined. The level of expression of NOVX mRNA or protein in the presence of the candidate compound is compared to the level of expression of NOVX mRNA or protein in the absence of the candidate compound. The candidate compound can then be identified as a modulator of NOVX mRNA or protein expression based upon this comparison. For example, when expression of NOVX mRNA or protein is greater (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.

[0274] 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 involved in the propagation of signals by the NOVX proteins as, for example, upstream or downstream elements of the NOVX pathway.

[0275] 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 a NOVX-dependent complex, the DNA-binding and activation domains of the transcription factor are brought into close proximity. This proximity allows transcription of a reporter gene (e.g., LacZ) that is operably linked to a transcriptional regulatory site responsive to the transcription factor. Expression of the reporter gene can be detected and cell colonies containing the functional transcription factor can be isolated and used to obtain the cloned gene that encodes the protein which interacts with NOVX.

[0276] The invention further pertains to novel agents identified by the aforementioned screening assays and uses thereof for treatments as described herein.

[0277] Detection Assays

[0278] 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.

[0279] Chromosome Mapping 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 of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 110, 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.

[0280] 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.

[0281] Somatic cell hybrids are prepared by fusing somatic cells from different mammals (e.g., human and mouse cells). As hybrids of human and mouse cells grow and divide, they gradually lose human chromosomes in random order, but retain the mouse chromosomes. By using media in which mouse cells cannot grow, because they lack a particular enzyme, but in which human cells can, the one human chromosome that contains the gene encoding the needed enzyme will be retained. By using various media, panels of hybrid cell lines can be established. Each cell line in a panel contains either a single human chromosome or a small number of human chromosomes, and a full set of mouse chromosomes, allowing easy mapping of individual genes to specific human chromosomes. See, e.g., D'Eustachio, et al., 1983. Science 220: 919-924. Somatic cell hybrids containing only fragments of human chromosomes can also be produced by using human chromosomes with translocations and deletions.

[0282] 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.

[0283] 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).

[0284] 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.

[0285] Once a sequence has been mapped to a precise chromosomal location, the physical position of the sequence on the chromosome can be correlated with genetic map data. Such data are found, e.g., in McKusick, MENDELIAN INHERITANCE IN MAN, available on-line through Johns Hopkins University Welch Medical Library). The relationship between genes and disease, mapped to the same chromosomal region, can then be identified through linkage analysis (co-inheritance of physically adjacent genes), described in, e.g., Egeland, et al., 1987. Nature, 325: 783-787.

[0286] 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.

[0287] Tissue Typing

[0288] 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).

[0289] 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.

[0290] 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).

[0291] 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 coding sequences, such as those of SEQ ID NO: 2n-1, wherein n is an integer between 1 and 110, are used, a more appropriate number of primers for positive individual identification would be 500-2,000.

[0292] Predictive Medicine

[0293] The invention also pertains to the field of predictive medicine in which diagnostic assays, prognostic assays, pharmacogenomics, and monitoring clinical trials are used for prognostic (predictive) purposes to thereby treat an individual prophylactically. Accordingly, one aspect of the invention relates to diagnostic assays for determining NOVX protein and/or nucleic acid expression as well as NOVX activity, in the context of a biological sample (e.g., blood, serum, cells, tissue) to thereby determine whether an individual is afflicted with a disease or disorder, or is at risk of developing a disorder, associated with aberrant NOVX expression or activity. The disorders include metabolic disorders, diabetes, obesity, infectious disease, anorexia, cancer-associated cachexia, cancer, neurodegenerative disorders, Alzheimer's Disease, Parkinson's Disorder, immune disorders, and hematopoietic disorders, and the various dyslipidemias, metabolic disturbances associated with obesity, the metabolic syndrome X and wasting disorders associated with chronic diseases and various cancers. The invention also provides for prognostic (or predictive) assays for determining whether an individual is at risk of developing a disorder associated with NOVX protein, nucleic acid expression or activity. For example, mutations in a 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.

[0294] 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 ag nts (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.)

[0295] 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.

[0296] These and other agents are described in further detail in the following sections.

[0297] Diagnostic Assays

[0298] 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 110, 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.

[0299] 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 (i.e., physically linking) a detectable substance to the probe or antibody, as well as indirect labeling of the probe or antibody by reactivity with another reagent that is directly labeled. Examples of indirect labeling include detection of a primary antibody using a fluorescently-labeled secondary antibody and end-labeling of a DNA probe with biotin such that it can be detected with fluorescently-labeled streptavidin. The term “biological sample” is intended to include tissues, cells and biological fluids isolated from a subject, as well as tissues, cells and fluids present within a subject. 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.

[0300] 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.

[0301] 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.

[0302] 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.

[0303] Prognostic Assays

[0304] 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.

[0305] 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).

[0306] The methods of the invention can also be used to detect genetic lesions in a 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 a 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 a NOVX gene; (ii) an addition of one or more nucleotides to a NOVX gene; (iii) a substitution of one or more nucleotides of a NOVX gene, (iv) a chromosomal rearrangement of a NOVX gene; (v) an alteration in the level of a messenger RNA transcript of a NOVX gene, (vi) aberrant modification of a 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 a NOVX gene, (viii) a non-wild-type level of a NOVX protein, (ix) allelic loss of a NOVX gene, and (x) inappropriate post-translational modification of a 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 a 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.

[0307] 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 a 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.

[0308] 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.

[0309] In an alternative embodiment, mutations in a 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.

[0310] 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.

[0311] 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).

[0312] 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.

[0313] 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 a 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.

[0314] 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.

[0315] 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.

[0316] 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.

[0317] 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.

[0318] 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 a NOVX gene.

[0319] 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.

[0320] Pharmacogenomics

[0321] Agents, or modulators that have a stimulatory or inhibitory effect on NOVX activity (e.g., NOVX gene expression), as identified by a screening assay described herein can be administered to individuals to treat (prophylactically or therapeutically) disorders. The disorders include but are not limited to, e.g., those diseases, disorders and conditions listed above, and more particularly include those diseases, disorders, or conditions associated with homologs of a NOVX protein, such as those summarized in Table A.

[0322] 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.

[0323] 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.

[0324] As an illustrative embodiment, the activity of drug metabolizing enzymes is a major determinant of both the intensity and duration of drug action. The discovery of genetic polymorphisms of drug metabolizing enzymes (e.g., N-acetyltransferase 2 (NAT 2) and cytochrome pregnancy zone protein precursor enzymes CYP2D6 and CYP2C19) has provided an explanation as to why some patients do not obtain the expected drug effects or show exaggerated drug response and serious toxicity after taking the standard and safe dose of a drug. These polymorphisms are expressed in two phenotypes in the population, the extensive metabolizer (EM) and poor metabolizer (PM). The prevalence of PM is different among different populations. For example, the gene coding for CYP2D6 is highly polymorphic and several mutations have been identified in PM, which all lead to the absence of functional CYP2D6. Poor metabolizers of CYP2D6 and 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.

[0325] 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 a NOVX modulator, such as a modulator identified by one of the exemplary screening assays described herein.

[0326] Monitoring of Effects During Clinical Trials

[0327] 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.

[0328] 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.

[0329] 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 a NOVX protein, mRNA, or genomic DNA in the preadministration sample; (iii) obtaining one or more post-administration samples from the subject; (iv) detecting the level of expression or activity of the NOVX protein, mRNA, or genomic DNA in the post-administration samples; (v) comparing the level of expression or activity of the NOVX protein, mRNA, or genomic DNA in the pre-administration sample with the NOVX protein, mRNA, or genomic DNA in the post administration sample or samples; and (vi) altering the administration of the agent to the subject accordingly. For example, increased administration of the agent may be desirable to increase the expression or activity of NOVX to higher levels than detected, i.e., to increase the effectiveness of the agent. Alternatively, decreased administration of the agent may be desirable to decrease expression or activity of NOVX to lower levels than detected, i.e., to decrease the effectiveness of the agent.

[0330] Methods of Treatment

[0331] 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 but are not limited to, e.g., those diseases, disorders and conditions listed above, and more particularly include those diseases, disorders, or conditions associated with homologs of a NOVX protein, such as those summarized in Table A.

[0332] These methods of treatment will be discussed more fully, below.

[0333] Diseases and Disorders

[0334] 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.

[0335] 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.

[0336] 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).

[0337] Prophylactic Methods

[0338] 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, a 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.

[0339] Therapeutic Methods

[0340] 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 a NOVX protein, a peptide, a 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 a 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 a NOVX protein or nucleic acid molecule as therapy to compensate for reduced or aberrant NOVX expression or activity.

[0341] 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).

[0342] Determination of the Biological Effect of the Therapeutic

[0343] 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.

[0344] 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.

[0345] Prophylactic and Therapeutic Uses of the Compositions of the Invention

[0346] The NOVX nucleic acids and proteins of the invention are useful in potential prophylactic and therapeutic applications implicated in a variety of disorders. The disorders include but are not limited to, e.g., those diseases, disorders and conditions listed above, and more particularly include those diseases, disorders, or conditions associated with homologs of a NOVX protein, such as those summarized in Table A.

[0347] 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 diseases, disorders, conditions and the like, including but not limited to those listed herein.

[0348] 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.

[0349] 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

[0350] Polynucleotide and Polypeptide Sequences, and Homology Data

Example 1

[0351] 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	1808 bp
NOV1a,	CGATCGCAGAGAGGCTGGAGTGTGCTACCGACGTCGAATATCCATGCAGACTAGAAGAGTATAATCTG
CG105324-01
DNA Sequence	GGTCCTTCCTGCAGGACAGTGCCTTGGTAATGACCACGGCTCCAGGAAGAGATGTCCTTGTGGCTGGG
	GGCCCCTGTGCCTGACATTCCTCCTGACTCTCGGAAGGAGCTGTGGAAGCCAGGCGCACAGGATGCAA
	CCAGCCACGCCCAGGGAGGCAGCAGCTGCATCCTCAGAGACGAAGCCAGGATGCCCCACTCTGCTGGG
	GGTACTGCAGCGGTGGGGCTGGAGGCTGCAGACCCCACAGCCCTCCTCACCAGGGCAGAGCCCCCTTC
	AGAACCCACAGAGATCCGTCCACAAAAGCGGAAAAAGGGGCCAGCCCCCAAAATGCTGGGGAACGAGC
	TATGCAGCGTGTGTGGGGACAAGGCCTCGGGCTTCCACTACAATGTTCTGAGCTGCGAGGGCTCCAAC
	GCATTCTTCCGCCGCAGCGTCATCAAGGGAGCGCACTACATCTGCCACAGTGGCGGCCACTGCCCCAT
	GGACACCTACATGCGTCGCAAGTGCCAGGAGTGTCGGCTTCGCAAATGCCGTCAGGCTGGCATGCGGG
	AGGAGTGTGTCCTGTCAGAAGAACAGATCCGCCTGAAGAAACTGAAGCGGCAAGAGGAGGAACAGGCT
	CATGCCACATCCTTGCCCCCCAGGCGTTCCTCACCCCCCCAAATCCTGCCCCAGCTCAGCCCGGAACA
	ACTGGGCATGATCGAGAAGCTCGTCGCTGCCCAGCAACAGTCTAACCGGCGCTCCTTTTCTGACCGGC
	TTCGAGTCACGCCTTGGCCCATGGCACCAGATCCCCATAGCCGGGACGCCCGTCAGCAGCGCTTTGCC
	CACTTCACTGAGCTGGCCATCGTCTCTGTGCAGGAGATAGTTGACTTTGCTAAACAGCTACCCGGCTT
	CCTGCAGCTCAGCCGGGAGGACCAGATTGCCCTGCTGAAGACCTCTGCGATCGAGGTGATGCTTCTGG
	AGACATCTCGGAGGTACAACCCTCGGAGTGAGAGTATCACCTTCCTCAAGGATTTCAGTTATAACCGG
	GAAGACTTTGCCAAAGCAGGGCTGCAAGTGGAATTCATCAACCCCATCTTCGAGTTCTCCAGGGCCAT
	GAATGAGCTGCAACTCAATGATGCCGAGTTTGCCTTGCTCATTGCTATCAGCATCTTCTCTGCAGACC
	GGCCCAACGTGCAGGACCAGCTCCAGGTAGAGAGGCTGCAGCACACATATGTGGAAGCCCTGCATGCC
	TACGTCTCCATCCACCATCCCCATGACCGACTGATGTTCCCACCGATGCTAATGAAACTGGTGAGCCT
	CCGGACCCTGAGCAGCGTCCACTCAGAGCAAGTGTTTGCACTGCGTCTGCAGGACAAAAAGCTCCCAC
	CGCTGCTCTCTGAGATCTGCGATGTGCACGAATGACTGTTCTGTCCCCATATTTTCTGTTTTCTTGGC
	CGGATGGCTGAGOCCTGGTGGCTGCCTCCTAGAAGTGGAACAGACTGAGAAGGGCAAACATTCCTGGG
	AGCTGGGCAAGGAGATCCTCCCGTGGCATTAAAAGAGAGTCAAAGGGTTGCGAGTTTTGTGGCTACTG
	AGCAGTGGAGCCCTCGCTAACACTGTGCTGTGTCTGAAGATCATGCTGACCCCACAAACGGATGGGCC
	TGGGGGCCACTTTGCACACGGTTCTCCAGAGCCCTCCCCATCCTGCCTCCACCACTTCCTGTTTTTCC
	CACACGGCCCCAAGAAAAATTCTCCACTGTCAAAAAAAAA
	ORF Start: ATG at 120		ORF Stop: TGA at 1461
	SEQ ID NO: 2	447 aa	MW at 50480.3kD
NOV1a,	MSLWLGAPVPDIPPDSAVELWKPGAQDASSQAQGGSSCILREEARMFHSAGGTAGVGLEAAEPTALLT
CG105324-O1
Protein	RAEPPSEPTETRPQKRKKGPAPKMLGNELCSVCGDKASGFHYNVLSCEGCKGFFRRSVIKGAHYICHS
Sequence
	GGHCPMDTYMRRKCQECRLRKCRQAGMREECVLSEEQIRLKKLKRQEEEQAHATSLPPRRSSPPQILP
	QLSPEQLGMIERLVAAQQQCNRRSFSDRLRVTPWPMAPDPHSREARQQRFAHFTELAIVSVQEIVDFA
	KQLPGFLQLSREDQIALLKTSAILTMLLETSRRYNPGSESITFLKDFSYNREDFAKAGLQVEFINPIF
	EFSRAMNELQLNDAEFALLIAISIFSADRPNVQDQLQVERLQHTYVEALHAYVSIHHPHDRLMFPRML
	MXLVSLRTLSSVHSEQVFALRLQDKKLPPLLSEIWDVHE
	SEQ ID NO:3	1461 bp
NOV1b,	CCCCCAAAAATGTCGTAACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAG
212779039
DNA Sequence	GTCTATATAAGCAGAGCTCTCTGGCTAACTAGAGAACCCACTGCTTACTGGCTTATCGAAATTAATA
	CGACTCACTATAGGGAGACCCAAGCTGGCTAGCGTTTAAACTTAAGCTTGGTACCGAGCTCGGATCC
	ACCATGTCCTTGTGGCTGGGGGCCCCTGTGCCTGACATTCCTCCTGACTCTGCGGTGGAGCTGTGGA
	AGCCAGGCGCACAGGATGCAAGCAGCCAGGCCCACGGAGGCAGCAGCTGCATCCTCAGAGAGGAAGC
	CAGGATGCCCCACTCTGCTGGGGGTACTGCAGGGGTGOGGCTGGAGGCTGCAGAGCCCACAGCCCTG
	CTCACCACGGCACAGCCCCCTTCAGAACCCACAGGTGTCCTGTCAGAAGAACAGATCCGCCTGAAGA
	AACTGAAGCGGCAAGAGGAGGAACAGGCTCATGCCACATCCTTGCCCCCCACGGCTTCCTCACCCCC
	CCAAATCCTGCCCCAGCTCAGCCOGGAACAACTGGGCATGATCCAGAAGCTCGTCGCTGCCCAGCAA
	CAGTCTAACCGGCGCTCCTTTTCTGACCGGCTTCCAGTCACGCCTTGGCCCATCGCACCAGATCCCC
	ATAGCCGGGAGGCCCGTCAGCAGCGCTTTGCCCACTTCACTGAGCTGGCCATCGTCTCTGTGCAGGA
	GATAGTTGACTTTGCTAAACAGCTACCCGGCTTCCTCCACCTCAGCCGGGAGGACCAGATTCCCCTG
	CTGAAGACCTCTGCGATCGACGTGATGCTTCTGGAGACATCTCGGAGGTACAACCCTGGGAGTGAGA
	GTATCACCTTCCTCAAGGATTTCAGTTATAACCGGGAAGACTTTGCCAAAGCAGGGCTGCAAGTGGA
	ATTCATCAACCCCATCTTCGAGTTCTCCAGGGCCATGAATGAGCTGCAACTCAATGATGCCGAGTTT
	GCCTTGCTCATTGCTATCAGCATCTTCTCTGCAGACCGGCCCAACGTGCAGGACCAGCTCCAGGTAG
	AGAGGCTGCAGCACACATATGTGGAAGCCCTCCATGCCTACGTCTCCATCCACCATCCCCATGACCG
	ACTGATGTTCCCACGGATGCTAATGAAACTGGTGAGCCTCCCGACCCTGAGCAGCGTCCACTCAGAG
	CAAGTGTTTGCACTGCGTCTGCAGGACAAAAAGCTCCCACCGCTGCTCTCTGAGATCTGGGATGTGC
	ACGAATGAGCGGCCGCTCGAGTCTAGAGGGCCCGTTTAAACCCGCTCATCAGCCTCGACTGTGCCTT
	CTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTTGACCCTGGAAGGTGCCACTCC
	CACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTGAGTTAGGA
	ORF Start: at 148		ORF Stop: TGA at 1279
	SEQ ID NO: 4	377 aa	MW at 42216.6kD
NOV1b,	GDPSWLAFKLKLGTELGSTMSLWLGAPVPDIPPDSAVELWKPGAQDASSQAQGOSSCILREEARMPH
212779039
Protein	SAGGTAGVGLEAAEPTALLTRAEPPSEPTGVLSEEQIRLKKLKRQEEEQAHATSLPPRASSPPQILP
Sequence
	QLSPEQLGMIEKLVAAQQQCNRRSFSDRLRVTPWPMAPDPHSREARQQRFAHFTELAIVSVQEIVDF
	AKQLPGFLQLSREDQIALLKTSAIEVMLLETSRRYNPGSESITFLKDFSYNREDFAKAGLQVEFINP
	IFEFSRAMNELQLNDAEFALLIAISIFSADRPNVQDQLQVERLQHTYVEALHAYVSTHHPHDRLMFP
	SEQ ID NO:5	1808 bp
NOV1c,	CGATCGGAGAGAGGCTGGAGTGTGCTACCGACGTCGAATATCCATGCAGACTAGAGTATAATCTG
CG105324-01
DNA Sequence	GGTCCTTCCTGCAGGACAGTGCCTTGGTAATGACCAGGCCTCCAGCAAGAGATGTCCTTGTGGCTGGG
	GGCCCCTGTGCCTGACATTCCTCCTGACTCTGCGGTGGAGCTGTGGAAGCCAGGCGCACAGGATGCAA
	GCAGCCAGGCCCAGGGAGGCAGCAGCTGCATCCTCAGAGAGGAAGCCAGGATGCCCCACTCTGCTGGG
	GGTACTGCAGGGGTGGGGCTGGAGGCTGCAGAGCCCACAGCCCTCCTCACCAGGGCAGAGCCCCCTTC
	AGAACCCACAGAGATCCGTCCACAAAAGCGGAAAAAGGGGCCAGCCCCCAAAATGCTGGGGAACGAGC
	TATGCAGCGTGTGTGGGGACAAGGCCTCGGGCTTCCACTACGTGTTCTGAGCTGCGAGGGCTGCATGC
	GGATTCTTCCGCCGCAGCGTCATCAAGGGAGCGCACTACATCTGCCACAGTGGCGGCCACTGCCCCAT
	GGACACCThCATGCGTCGCAAGTGCCAGGGAGTGTCGGCTTCCCGATGCCGTCAGGCTGGCATCCGGG
	AGGAGTGTGTCCTGTCAGAAGAACAGATCCGCCTGAAGAAACTGAAGCGGCAAGAGGAGGAACAGGCT
	CATGCCACATCCTTGCCCCCCAGGCGTTCCTCACCCCCCCTTCCTCCCCCAGCTCAGCCCGGAACACA
	ACTGGGCATGATCGAGAGGCTCGTCGCTGCCCAGCAACAGTGTAACCGGCGCTCCTTTTCTGACCGGC
	TTCGAGTCACGCCTTGGCCCATGGCACCAGATCCCCATAGCCGGGAGGCCCGTCAGCAGCGCTTTGCC
	CACTTCACTGAGCTGGCCATCGTCTCTGTGCAGGAGATAGTTGACTTTGCTAAACAGCTACCCGGCTT
	CCTGCAGCTCAGCCGGGACGACCAGATTGCCCTGCTGAAGACCTCTGCGATCGAGGTGATGCTTCTGG
	AGACATCTCGGAGGTACAACCCTGGGAGTGAGAGTATCACCTTCCTCAAGGATTTCAGTTATGCCCGG
	GAAGACTTTGCCAAAGCAGGGCTGCAAGTGGAATTCATCAACCCCATCTTCGAGTTCTCCAGGGCCAT
	GAATGAGCTGCAACTCAATGATGCCGAGTTTGCCTTCCTCATTCCTATCAGCATCTTCTCTGCAGACC
	GGCCCAACGTGCAGGACCAGCTCCAGGTAGAGAGGCTGCAGCACACATATGTGGTCGCCCTGCATGCC
	TACGTCTCCATCCACCATCCCCATGACCGACTGATGTTCCCACGGATGCTAATGAAACTGGTGAGCCT
	CCGGACCCTGAGCAGCGTCCACTCAGAGCAAGTGTTTGCACTGCGTCTGCAGCACGCTAHGCTCCCAC
	CGCTGCTCTCTGAGATCTGGGATGTGCACGAATGACTGTTCTGTCCCCATATTTTCTGTTTTCTTGCC
	GGATGGCTGAGGCCTGGTGGCTGCCTCCTAGAAGTGGAACAGACTGAGATTGGGCGCACATTCCTGGC
	AGCTGGGCAAGGAGATCCTCCCGTGGCATTAGAGAGAGTCGTAAGGGTTGCGAGTTTTGTGGCTACTG
	AGCAGTGGAGCCCTCGCTAACACTGTGCTGTGTCTGAAGATCATGCTGACCCCACGCTCGGATGGGCC
	TGGGGGCCACTTTGCACAGGGTTCTCCAGAGCCCTGCCCATCCTGCCTCCACCACTTCCTGTTTTTCC
	CACAGGGCCCCAAGAAAATTCTCCACTGTCAAAAAAAAAA
	ORF Start: ATG at 120		RF Stop: TGA at 1461
	SEQ ID NO: 6	447 aa	MW at 50480.3kD
NOV1c,	MSLMLGAPVPDIPPDSAVELWKPGAQDASSQAQGGSSCILREEARMPHSAGGTAGVGLEAAEPTALLT
CG105324-01
Protein	RAEPPSEPTEIRPQKRKKGPAPKMLGNELCSVCGDKASGFHYNVLSCEGCKGFFRRSVIKGAHYICHS
Sequence
	GGHCPMDTYMRRKCQECRLRKCRQAGMREECVLSEEQIRLKKLKRQEEEQAHATSLPPRRSSPPQILP
	QLSPEQLGMIEKLVAAQQQCNRRSFSDRLRVTPWPMAPDPHSREQQRFAHFTELHFAIVSVQEIVDFA
	KQLPGFLQLSREDQIALLKTSAIEVMLLETSRRYNPGSESITFLKDFSYNREDFAKAGLQVEFINPIF
	EFSRAMNELQLNDAEFALLIAISIFSADRPNVQDQLQVERLQHTYVEALHAYVSIHHPHDRLMFPRML
	MKLVSLRTLSSVHSEQVFALRLQDKKLPPLLSEIWDVHE
	SEQ ID NO:7	1374bp
NOV1d,	CGCGGATCCACCATGTCCTTGTGGCTGGGGGCCCCTGTGCCTGACATTCCTCCTGACTCTGCGGTGG
209829541
DNA Sequence	AGCTGTGGAAGCCAGCCGCACAGGATGCAAGCAGCCAGGCCCAGGGAGGCAGCAGCTGCATCCTCAG
	AGAGGAAGCCAGGATGCCCCACTCTGCTGGGGGTACTGCAGGGGTGGGGCTGGAGGCTGCAGAGCCC
	ACAGCCCTGCTCACCAGGGCAGAGCCCCCTTCAGTACCCACAGAGATCCGTCCACAAAAGCGGAAAA
	AGGGGCCAGCCCCCAAAATGCTGGGGAACGAGCTATGCAGTGTGTGTGGGGACAAGGCCTCGGGCTT
	CCACTACAATGTTCTGAGCTGCGAGGGCTGCATCGGGATTCTTCCGCCGCAGCGTCATCGGATAGCG
	CACTACATCTGCCACAGTGGCGGCCACTGCCCCATGGACACCTACATGCGTCGCAAGTGCCAGAAGT
	GTCGGCTTCGCAAATGCCGTCAGGCTGGCATGCGGACGAGTGTGTCCTGTCAGTCGAGTCAGATCCG
	CCTGAAGAAACTGAGCGCAAGAGGAGGAACAAATGCTCATGCCACATCCTTGCCCCCCAAGCATTCC
	TCACCCCCCCAATCCTGCCCCAGCTCAGCCCGGAACAACTGGGCATGATCGAGAAGCATCGTCGCTG
	CCCAGCAACAGTGTAACCGGCGCTCCTTTTCTGACCGGCTTCGAGTCACGCCTTGGCCCATGGCACC
	AGATCCCCATAGCCGGGAGGCCCGTCACCAGCGCTTTGCCCACTTCACTGACCTGCCCATCGTCTCT
	GTGCAGGAGATAGTTGACTTTGCTAAACAGCTACCCGGCTTCCTGCAGCTCAGCCGTAGGAGCCAGA
	TTGCCCTGCTGATGACCTCTOCCATCCAGGTGATGCTTCTGGAGACATCTCGGAGGTACATCCCTGA
	GAGTGAGAGTATCACCTTCCTCAAGGATTTCAGTTATAACCGGGAAGACTTTGCCAAAGCAGGGCTG
	CAAGTGGAATTCATCAACCCCATCTTCGAGTTCTCCAGGGCCATGAATGAGCTGCAACTCAATGATG
	CCGAGTTTGCCTTGCTCATTGCTATCAGCATCTTCTCTGCAGACCGGCCCAACGTGCAGGACCAGCT
	CCAGGTAGAGAGGCTGCAGCACACATATGTGGAAGCCCTGCATGCCTACGTCTCCATCCACCATCCC
	CATGACCGACTGATGTTCCCACGGATGCTAATGAAACTGGTGAGCCTCCCGACCCTGAGCAGCCTCC
	ACTCACAGCAAGTGTTTGCACTGCGTCTGCAGGACAAAAAGCTCCCACCGCTGCTCTCTGAGATCTG
	GGATGGGCACGAATGAGCGGCCGCTTTTTTCCTT
	ORF Start: at 1		ORF Stop: TGA at 1354
	SEQ ID NO: 8	451 aa	MW at 50796.6kD
NOV1d,	RGSTMSLWLGAPVPDIPPDSAVELWKPGAQDASSQAQGGSSCILREEARMPHSAGCTAGVGLEAAEP
209829541
Protein	TALLTRAEPPSEPTEIRPQKRKKGPAPKMLGNELCSVCGDKASGFHYNVLSCEGCKGFFRRSVIKGA
Sequence
	HYICHSGGHCPMDTYNRRKCQECRLRKCRQAGMREECVLSEEQIRLKKLKRQEEEQAHATSLPPRAS
	SPPQILPQLSPEQLGMIEKLVAAQQQCNRRSTSDRLRVTPWPMAPDPHSREARQQRFAHFTELAIVS
	VQEIVDFAXQLPGFLQLSREDQIALLKTSAIEVMLLETSRRYNPGSESITFLKDFSYNREDFAKAGL
	QVEFINPIFEFSRAMNELQLNDAEFALLIAISIFSADRPNVQDQLQVERLQHTYVEALHAYVSIHHP
	HDRLMFPRMLMKLVSLRTLSSVHSEQVFALRLQDKKLPPLLSEIWDVHE

[0352] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 1B.

TABLE 1B
Comparison of NOV1a against NOV1b through NOVld.
			Identities/
			Similarities
	Protein	NOV1a Residues/	for the
	Sequence	Match Residues	Matched Region
	NOV1b	168 . . . 447	264/280 (94%)
		98 . . . 377	264/280 (94%)
	NOV1c	1 . . . 447	418/447 (93%)
		1 . . . 447	418/447 (93%)
	NOV1d	1 . . . 447	417/447 (93%)
		5 . . . 451	417/447 (93%)

[0353] Further analysis of the NOV1a protein yielded the following properties shown in Table 1C.

TABLE 1C
Protein Sequence Properties NOV1a
PSort analysis:   0.3000 probability located in nucleus;
                  0.1000 probability located in mitochondrial
                  matrix space; 0.1000 probability located in
                  lysosome (lumen); 0.0000 probability located
                  in endoplasmic reticulum (membrane)
SignalP analysis: No Known Signal Sequence Predicted

[0354] 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 1D.

TABLE 1D
Geneseq Results for NOVla
		NOV1a	Identities/
		Residues/	Similarities
Geneseq	Protein/Organism/Length	Match	for the	Expect
Identifier	[Patent #, Date]	Residues	Matched Region	Value
AAW03326	LXR-alpha, orphan member	1 . . . 447	447/447 (100%)	0.0
	of nuclear hormone receptor	1 . . . 447	447/447 (100%)
	superfamily - Homo sapiens,
	447 aa.[WO9621726-A1,
	18 JUL. 1996]
AAR33744	XR2 - Homo sapiens, 440 aa.	1 . . . 447	436/447 (97%)	0.0
	[WO9306215-A,	1 . . . 440	437/447 (97%)
	01 APR. 1993]
AAR88452	Retinoic acid receptor	1 . . . 447	422/447 (94%)	0.0
	epsilon -Homo sapiens, 433	1 . . . 433	425/447 (94%)
	aa.[WO9600242-A1,
	04 JAN. 1996]
AAY32374	Mouse CNREB-1 - Mus	1 . . . 447	409/447 (91%)	0.0
	musculus, 445 aa.	1 . . . 445	421/447 (93%)
	[WO9955343-A1,
	04 NOV. 1999]
AAR74738	Human ubiquitous nuclear	14 . . . 447	287/460 (62%)	e−154
	receptor protein - Homo	4 . . . 460	338/460 (73%)
	sapiens, 460 aa.
	[WO9513373-A1,
	18 MAY. 1995]

[0355] In a BLAST search of public sequence datbases, the NOV1a protein was found to

TABLE 1E
Public BLASTP Results for NOV1a
		NOV1a	Identities/
Protein		Residues/	Similarities
Accession		Match	for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
Q13133	Oxysterols receptor LXR-alpha	1 . . . 447	447/447 (100%)	0.0
	(Liver X receptor alpha) (Nuclear	1 . . . 447	447/447 (100%)
	orphan receptor LXR-alpha) -
	Homo sapiens (Human), 447 aa.
Q9Z0Y9	Oxysterols receptor LXR-alpha	1 . . . 447	410/447 (91%)	0.0
	(Liver X receptor alpha) (Nuclear	1 . . . 445	422/447 (93%)
	orphan receptor LXR-alpha) -
	Mus musculus (Mouse), 445 aa.
Q91X41	Similar to nuclear receptor	1 . . . 447	409/447 (91%)	0.0
	subfamily 1, group H, member 3 -	1 . . . 445	421/447 (93%)
	Mus musculus (Mouse), 445 aa.
Q62685	Oxysterols receptor LXR-alpha	1 . . . 447	408/447 (91%)	0.0
	(Liver X receptor alpha) (Nuclear	1 . . . 445	420/447 (93%)
	orphan receptor LXR-alpha) (RLD-1) -
	Rattus norvegicus (Rat), 445 aa.
AAM90897	Liver X receptor - Gallus gallus	62 . . . 447	310/386 (80%)	0.0
	(Chicken), 409 aa.	24 . . . 409	341/386 (88%)

[0356] PFam analysis predicts that the NOV1a protein contains the domains shown in the Table 1F.

TABLE 1F
Domain Analysis of NOV1a
		Identities/
	NOV1a	Similarities
	Match	for the	Expect
Pfam Domain	Region	Matched Region	Value
zf-C4	96 . . . 171	43/77 (56%)	3.4e−41
		64/77 (83%)
hormone_rec	262 . . . 443	63/207 (30%)	1.7e−53
		148/207 (71%)

Example 2

[0357] 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:9	5864 bp
NOV2a,	CACTCGCTGGGGAGTCCCGTCGACGCTCTGTTCCGAGAGCGTGCCCCGGACCGCCAGCTCAGAACAGC
CG105355-01
DNA Sequence	GGCAGCCGTGTAGCCGAACGGAAGCTGGGAGCAGCCGGGACTGGTGGCCCGCGCCCGGAGCTCCGCAGG
	CGGGAACCACCCTGGATTTGGGAAGTCCCGGGACCAGCGCGGCGGCACCTCCCTCACCCAAGGGGCCG
	CGGCGACGGTCACGGGGCGCGGCGCCACCGTGAGCGACCCAGGCCAGGATTCTAAATACACGGCCCAG
	GCTCCTCCTCCGCCCGGGCCGCCTCACCTGCGGGCATTGCCGCGCCGCCTCCGCCGGTGTAGACGCCA
	CCTGCGCCGCCTTGCTCGCGOGTCTCCGCCCCTCGCCCACCCTCACTGCGCCAGGCCCAGGCAGCTCA
	CCTGTGCTGGCGCGGGCTGCGGAAGCCTGCGTGAGCCGAGGCGTTGAGGCGCGGCGCCCACGCCACTG
	TCCCGAGAGGACGCAGGTGGAGCGGGCGCGGCTTCGCGGAACCCGGCGCCGGCCGCCGCAGTGGTCCC
	AGCCTACACCGGGTTCCGGGGACCCGGCCGCCAGTGCCCGGGGAGTAGCCGCCGCCGTCGGCTGGGCA
	CCATGAACAGCAGCAOCGCCAACATCACCTACGCCAGTCGCAAGCGGCGGAAGCCGGTGCAGAAAACA
	GTAAAGCCAATCCCAGCTGAAGGAATCAAGTCAAATCCTTCCAAGCGGCATAGA~ACCGACTTAATAC
	AGAGTTGGACCGTTTGGCTAGCCTGCTGCCTTTCCCACAAGATGTTATTAATAAGTTGGACAAACTTT
	CAGTTCTTAGGCTCAGCGTCAGTTACCTGAGAGCCAAGAGCTTCTTTGATGTTGCATTAAAATCCTCC
	CCTACTGAAAGAAACGGAGGCCAGGATAACTGTAGAGCAGCAAATTTCAGAGAAGGCCTGAACTTACA
	AGAAGGAGAATTCTTATTACAGGCTCTGAATGGCTTTGTATTAGTTGTCACTACAGATGCTTTGGTCT
	TTTATGCTTCTTCTACTATACAAGATTATCTAGGGTTTCAGCAGTCTGATGTCATACATCAGAGTGTA
	TATGAACTTATCCATACCGAAGACCGAGCTGAATTTCAGCGTCAGCTACACTGGGCATTAAATCCTTC
	TCAGTGTACAGAGTCTGGACAAGGAATTGAAGAAGCCACTGGTCTCCCCCAGACAGTAGTCTGTTATA
	ACCCAGACCAGATTCCTCCAGAAAACTCTCCTTTAATGGAGAGGTGCTTCATATGTCGTCTAATGTGT
	CTGCTGGATAATTCATCTGGTTTTCTGGCAATGAATTTCCAAGGGAAGTTAAAGTATCTTCATCGACA
	GAAAAAGAAAGGGAAAGATGGATCAATACTTCCACCTCAGTTGGCTTTGTTTGCGATAGCTACTCCAC
	TTCAGCCACCATCCATACTTGAAATCCGGACCAAAAATTTTATCTTTAGAACCAGACACAAACTAGAC
	TTCACACCTATTGGTTGTGATGCCAAAGGAAGAATTGTTTTACGATATACTGAAGCAGAGCTGTGCAC
	GAGAGGCTCAGGTTATCAGTTTATTCATGCAGCTGATATGCTTTATTGTGCCGAGTCCCATATCCGAA
	TGATTAAGACTGGAGAGGAGTGGCATGATAGTTTTCCGGCTTCTTACAAAAACAACCGATGGACTTGG
	GTCCAGTCTAATGCACGCCTGCTTTATAAAAATGGAAGACCAGATTATATCATTGTAACTCAGAGACC
	ACTAACAGATGAGGAAGGAACAGAGCATTTACGAAAACGAAATACGAAGTTGCCTTTTATGTTTACCA
	CTGGAGAAGCTGTGTTGTATGAGGCACCAACCCTTTTCCTGCCATAATGGATCCCTTACCACTAGGGG
	ACTAAAAATGGCACTAGTGGAAAAGACTCTGCTACCACATCCACTCTAAGCAAGGACTCTCTCGATCC
	TAGTTCCCTCCTGGCTGCCATCATGCAACAAGATGAGTCTATTTATCTCTATCCTGCTTCAAGTACTT
	CAAGTACTGCACCTTTTGAAAACAACTTTTTCAACGAATCTATGAATGAATGCAGATTGATTGGATAT
	AATACTGCACCGATGGGAAATGATACTATCCTGAAACATGAGCAAATTGACCAGCCTGAGGATGTGAT
	CTCATTTGCTGGAGGTCACCCAGGGCTCTTTCAAGATAGTAAAACAGTGACTTGTACAGCATGATTGA
	AAAACCTAGGCATTGATTTTGAAGACATCAGACACATGCAGAATGAAAAATTTTTCAGAATGAGTTTT
	TCTGGTGAGGTTGACTTCAGAGACATTGACTTAACGGATGAAATCCTGACGTATGTGATGATTCTTTT
	AAGTAAGTCTCCCTTCATACCTTCAGATTATCAACAGCAACAGTCCTTGGCTCTGAACTCAAGCTGTA
	TGGTACAGGAACACCTACTATCTAGAACAGCAACAGCAACATCACCAAAGCAAGTAGTAGTGGAGCCA
	CAGCAACAGCTGTGTCAGAAGATGAAGCACATGCAAGTTAATGGCATGTTGAAAATTGGAACATCTAA
	CCAATTCGTGCCTTTCAATTGTCCACAGCAAGACCCACAACAATATAATGTCTTTACAGACTTACATG
	GGATCAGTCAAGAGTTCCCCTACAAATCTGAAATGGATTCTATGCCTTATACACAGAGCTTTATTTCC
	TGTAATCAGCCTGTATTACCACAACATTCCAAATGTACAGAGCTGGACTACCCTATGGGGAGTTTTGA
	ACCATCCCCCATACCCCACTACTTCTAGTTTAGAAGATTTGTCACTTGTTTACAACTTCCTGAAAACC
	AAAAGCATGGATTAAATCCACAGTCAGCCATAATAACTCCTCAGACATGTTATGCTGGGGCCGTGTCG
	ATGTATCAGTGCCAGCCAGAACCTCAGCACACCCACGTGGGTCAGATGCAGTACAATCCAGTACTGCC
	AGCCCAACAGCCATTTTTAAACAAGTTTCAGAATGGAGTTTTAATGAACATATCCAGCTGAAATTTAA
	ATAACATAAATAACACTCAGACTACCACACATCTTCAGCCACTTCATCATCCGTCAGAGCCAGACACT
	TTTCCTGATTTGACATCCAGTGGATTCCTGTAATTCCAAGCCCAATTTTGACCCTGGTTTTTGGATTA
	AATTAGTTTGTGAAGGATTATGCAAAAATAAAACTGTCACTGTTGGACGTCAGCAAGTTCACATGGAG
	GCATTGATGCATGCTATTCACAATTATTCCAAACCAATTTTAATTTTTCCTTTTAAGAAAAGGGAGTT
	TAAAAATGGTATCAAAATTACATATACTACAGTCAAGATAGATAGGGTGCTCCCACGGAGTGGTGAGG
	TACCGTCTACATTTCACATTATTCTGGGCACCACAAAATATACATACTTTATCAGGGAACTAAGCGAT
	TCTTTTAAATTAGAAAATATTCTCTATTTGAATTATTTCTGTCACAGTAAAAAGATTATACTTTGAGT
	TTTGAGCTACTGGATTCTTATTAGTTCCCCAAATACAAAGTTAGAGAACTATGCTAGTTTTTCCTATC
	ATGTTAACCTCTGCTTTTATCTCAGATGTTAAAATAAATGGTTTGGTGCTTTTTATAAAAAGATAATC
	TCAGTGCTTTCCTCCTTCACTGTTTCATCTAAGTGCCTCACATTTTTTTCTACCTATAACACTCTAGC
	ATGTATATTTTATATAAAGTATTCTTTTTCTTTTTTAAATTAATATCTTTCTGCACACAGTTATTATT
	TGTGTTTCCTAAATCCAACCATTTTCATTAATTCAGGCATATTTTAACTCCACTGCTTACCTACTTTC
	TTCAGGTAAAGGGCAAATAATCATCGAAAAAATAATTATTTATTACATAATTTAGTTGTTTCTAGACT
	ATAATGTTGCTATGTCCCTTATGTTGAAAAAATTTAAAAGTAAATGTCTTTCCAAAGCTTATTTCTTA
	ATTATTATAAAAATATTAAGACAATAGCACTTAAATTCCTCAACAGTGTTTTCAGAAGAAATAAATAT
	ACCACTCTTTACCTTTATTGATATCTCCATGATGATAGTTGAATGTTCCAATGTG~.AATCTGCTGT
	ATTTCAATGTCTATAAATTGTCTTTAAAAACTGTTTTAGACCTATAATCCTTGATAATATATTGTGTT
	GACGTTATAAATTTCGCTTCTTAGAACAGTGCAATCTATGTGTTTTTCTCATATTTGAGGAGTGTTTT
	GATTGCAGATAGCAAGGTTTCGTGCAAGTATTATAATGAGTGAATTGATGGTGCATTGTATAGATATA
	TAATGAACAAATTATTTGTAAGATATTTGCAGTTTTTCATTTTAAAAAGTCCATACCTTATAGTATGC
	ACTTAATTTGTTGGGGCTTTACATACTTTATCAATGTGTCTTTCTAAGAAATCAAGTAATGAATCCAA
	CTGCTTAAAGTTGGTATTAATAAAAAGACAACCACATACTTCGTTTACCTTCAAACTTTAGGTTTTTT
	TAATGATATACTGATCTTCATTACCAATAGGCAAATTAATCACCCTACCAACTTTACTGTCCTAACAT
	GGTTTAAAAGAAAAAATGACACCATCTTTTATTCTTTTTTTTTTTTTTTTTGAGAGAGAGTCTTACTC
	TGCCGCCCAACTGGAGTGCAGTCGCACAATCTTGGCTCACTGCAACCTCTACGCTCCTCGGTTCAAGT
	GATTCTCTTGCCTCAGCCTCCCGAGTTGCTGOGATTGCGGGCATGGTGGCGTGAGCCTGTAGTCCTAG
	CTACTCGGGAGGCTGAGGCAGGAGAATAGCCTGAACCTGGGAATCGGAGCTTCCAGGGcCAACATCGC
	CCCACTGCACTCCAGCCTGGCAATAGACCGAGACTCCGTCTCCAAAAAAAAAAAAAATACAATTTTTA
	TTTCTTTTACTTTTTTTAGTAAGTTAATGTATATAAAAATGGCTTCCGACAAAATATCTCTGAGTTCT
	GTGTATTTTCAGTCAAAACTTTAAACCTGTAGAATCAATTTAAGTGTTGGAAAAAATTTGTCTGAAAC
	ATTTCATAATTTGTTTCCAGCATGAGTATCTAAGGATTTAAAACCAGAGGTCTAGATTAATACTCTAT
	TTTTACATTTAAACCTTTTATTATAAGTCTTACATAAACCATTTTTGTTACTCTCTTCCACATGTTAC
	TGGATAAATTGTTTAGTGGAA~ATAGGCTTTTTAATCATGAATATGATGACAATCAGTTATACAGTTA
	TAAAATTAAAAGTTTGAAAAGCAATATTGTATATTTTTATCTATATAAAATAACTAAAATGTATCTAA
	GAATAATAAAATCACGTTAAACCAAATACACGTTTGTCTGTATTGTTAAGTGCCAAACAAAGGATACT
	TAGTGCACTGCTACATTGTGGGATTTATTTCTAGATGATGTGCACATCTAAGGATATGGATGTGTCTA
	ATTTTAGTCTTTTCCTGTACCAGGTTTTTCTTACAATACCTGAAGACTTACCAGTATTCTAGTGTATT
	ATGAAGCTTTCAACATTACTATGCACAAACTAGTGTTTTTCGATGTTACTAAATTTTAGGTAAATGCT
	TTCATGGCTTTTTTCTTCAAAATGTTACTGCTTACATATATCATGCATAGATTTTTGCTTAAAGTATG
	ATTTATAATATCCTCATTATCAAAGTTGTATACAATAATATATAATAAAATAACAAATATGAATAATA
	AAAAAAAAAAAAAAAA
	ORF Start: ATG at 615		ORF Stop: TAA at 3159
	SEQ ID NO: 10	848 aa	MW at 96146.5kD
NOV2a,	NNSSSANITYASRXRRKPVQKTVKPIPAEGIKSNPSKRHRDRLNTELDRLASLLPFPQDVINKLDKLS
CG105355-01
Protein	VLRLSVSYLRAKSFFDVALKSSPTERNGGQDNCRAANFREGLNLQEGEFLLQALNGFVLVVTTDALVF
Sequence
	YASSTIQDYLGFQQSDVIHQSVYELIHTEDRAEFQRQLHWALNPSQCTESGQGIEEATGLPQTVVCYN
	PDQIPPENSPLMERCFICRLRCLLDNSSGFLAMNFQGKLKYLHGQKKKGKDGSILPPQLALFAIATPL
	QPPSILEIRTKNFIFRTKHKLDFTPIGCDAKGRIVLGYTEAELCTRGSGYQFIHAADMLYCAESHIRM
	IKTGESGMIVFRLLTKNNRWTWVQSNARLLYKNGRPDYIIVTQRPLTDEEGTEHLRKRNTKLPFMFTT
	GEAVLYEATNPFPAIMDPLPLRTKNGTSGKDSATTSTLSKDSLNPSSLLAAMMQQDESIYLYPASSTS
	STAPFENNFFNESMNECRNWQDNTAPMGNDTILKHEQIDQPQDVNSFAGGHPGLFQDSKNSDLYSIMK
	NLGIDFEDIRHMQNEKFFRNDFSGEVDFRDIDLTDEILTYVQDSLSKSPFIPSDYQQQQSLALNSSCM
	VOEHLHLEOOOOHHOKOVVVEPOOOLCOKMKHMOVNGMFENWNSNOFVPFNCPOODPOOYNVFTDLHG
	ISQEFPYKSEMDSMPYTQNFISCNQPVLPQHSKCTELDYPMGSFEPSPYPTTSSLEDFVTCLQLPENQ
	KHGLNPQSAIITPQTCYAGAVSMYQCQPEPQHTHVGQMQYNPVLPGQQAFLNKFQNGVLNETYFAELN
	NINNTQTTTHLQPLHHPSEARPFPDLTSSGFL
	SEQ ID NO:11	2551 bp
NOV2b,	CACCATGAACAGCAGCAGCGCCAACATCACCTACGCCAGTCGCAAGCGGCGGAAGCCGGTGCAGAAA
245279626
DNA Sequence	ACAGTAAAGCCAATCCCAGCTGAAGGAATCAAGTCAAATCCTTCCAAGCGGCATAGAGACCGACTTA
	ATACAGAGTTGGACCGTTTGGCTAGCCTGCTGCCTTTCCCACAAGATGTTATTAATAAGTTGGACAA
	ACTTTCAGTTCTTAGGCTCAGCGTCAGTTACCTGAGAGCCAAGAGCTTCTTTGATGTTGCATTAAAA
	TCCTCCCCTACTGAAAGAAACGGAGGCCAGGATAACTGTAGAGCAGCAAATTTCAGAGAAGGCCTGA
	ACTTACAAGAAGGAGAATTCTTATTACAGGCTCTGAATGGCTTTGTATTAGTTGTCACTACAGATCC
	TTTGGTCTTTTATGCTTCTTCTACTATACAAGATTATCTAGGGTTTCAGCAGTCTGATGTCATACAT
	CAGAGTGTATATGAACTTATCCATACCGAAGACCGACCTGAATTTCAGCGTCAGCTACACTGCGCAT
	TAAATCCTTCTCAGTGTACAGAGTCTGGACAAGGAATTGAAGAAGCCACTGGTCTCCCCCAGACAGT
	AGTCTGTTATAACCCAGACCAGATTCCTCCAGAAAACTCTCCTTTAATGGAGAGGTGCTTCATATGT
	CGTCTAAGGTGTCTGCTGGATAATTCATCTGGTTTTCTGGCAATGAATTTCCAAGGGAAGTTAAAGT
	ATCTTCATGGACAGAAAAAGAAAGGGAAAGATGGATCAATACTTCCACCTCAGTTGGCTTTGTTTGC
	GATAGCTACTCCACTTCAGCCACCATCCATACTTGAAATCCGGACCAAAAATTTTATCTTTAGAACC
	AAACACAAACTAGACTTCACACCTATTGGTTGTGATGCCAAAGGAAGAATTGTTTTAGGATATACTG
	AAGCAGAGCTGTGCACGAGAGGCTCAGGTTATCAGTTTATTCATGCAGCTGATATGCTTTATTGTGC
	CGAGTCCCATATCCGAATGATTAAGACTGGAGAAAGTGGCATGATAGTTTTCCGGCTTCTTACAAAA
	AACAACCGATGGACTTGGGTCCAGTCTAATGCACGCCTGCTTTATAAAAATGGAAGACCAGATTATA
	TCATTGTAACTCAGAGACCACTAACAGATGAGGAAGGAACAGAGCATTTACGAAAACGAAATACGAA
	GTTGCCTTTTATGTTTACCACTGGAGAAGCTGTGTTGTATGAGGCAACCAACCCTTTTCCTGCCATA
	ATGGATCCCTTACCACTAAGGACTAAAAATGCCACTAGTGGAAAAGACTCTGCTACCACATCCACTC
	TAAGCAAGGACTCTCTCAATCCTAGTTCCCTCCTGGCTGCCATGATGCAACGAGATGAGTCTATTTA
	TCTCTATCCTGCTTCAAGTACTTCAAGTACTGCACCTTTTGAAACAACTTTTGTCAACGAATCTATG
	AATGAATGCAGAAATTGGCAAGATAATACTGCACCGATCGGAAATGATACTATCCTGAGCCATGAGC
	AAATTGACCAGCCTCAGGATGTGAACTCATTTGCTGGAGGTCACCCAGGGCTCTTTCAAGATAGTAA
	AAACAGTGACTTGTACAGCATAATGAAAAACCTAGGCATTGATTTTGAAGACATCAGACACATGCAG
	AATGAAAAATTTTTCAGAAATGATTTTTCTGGTGAGGTTGACTTCAGAGACATTGACTTAACGGATG
	AATCCTGACGTATGTCCAAGATTCTTTAAGTAAGTCTCCCTTCATACCTTCAGATTATCAAACAGCA
	ACAGTCCTTGGCTCTGAACTCAAGCTGTATGGTACAGGAACACCTACATCTAGAACAGCAACAGCAA
	CATCACCAAAAGCAAGTAGTAGTGGAGCCACAGCAACAGCTGTGTCAGAAGATGAACCACATGCAAG
	TTAATGGCATGTTTGAAAATTGGAACTCTAACCAATTCGTGCCTTTCAATTGTCCACAGCAAGACCC
	ACAACAATATAATGTCTTTACAGACTTACATGGGATCAGTCAAGAGTTCCCCTACAAATCTGAAATG
	GATTCTATGCCTTATACACAGAACTTTATTTCCTGTAATCAGCCTGTATTACCACAACATTCCAAAT
	GTACAGAGCTGGACTACCCTATGGGGAGTTTTGAACCATCCCCATACCCCACTACTTCTAGTTTAGA
	AGATTTTGTCACTTGTTTACAACTTCCTGAAACCAAAAGCATGGATTAAATCCACAGGTCAGCCATA
	ATAACTCCTCAGACATGTTATGCTGGGGCCGTGTCGATGTATCAGTGCCAGCCAGAACCTCAGCACA
	CCCACGTGGGTCACATGCAGTACAATCCAGTACTGCCAGGCCAAACAGGCATTTTTAACAAGTTTCA
	GAATGGAGTTTTAAATGAAACATATCCAGCTGAATTAAATAACATAAATAACACTCAGACTACCACA
	CATCTTCAGCCACTTCATCATCCGTCAGAAGCCAGACCTTTTCCTGATTTGACATCCAGTGGATTCC
	TGTAA
	ORF Start: at 2		ORF Stop: TAA at 2549
	SEQ ID NO: 12	849 aa	MW at 96247.6kD
NOV2b,	TMNSSSANITYASRKRRKPVQKTVKPIPAEGIKSNPSKRHRDRLNTELDRLASLLPFPQDVINKLDK
245279626
Protein	LSVLRLSVSYLRAKSFFDVALKSSPTERNCOQDNCRAANFREGLNLQEGEFLLQALNGFVLVVTTDA
Sequence
	LVFYASSTIQDYLGFQQSDVIHQSVYELIHTEDRAEFQRQLHWALNPSQCTESGQGIEEATGLPQTV
	VCYNPDQTPPENSPLMERCFICRLRCLLDNSSGFLAMNFQGKLKYLHGQKKKGKDGSILPPQLALFA
	IATPLQPPSILEIRTKNFIFRTKHKLDFTPTGCDAKGRIVLGYTEAELCTRGSGYQFIHAADMLYCA
	ESHIRMIKTGESGMIVFRLLTKNNRWTWVQSNARLLYKNGRPDYIIVTQRPLTDEEGTEHLRKRNTK
	LPFMFTTGEAVLYEATNPFPAIMDPLPLRTKNGTSGKDSATTSTLSKDSLNPSSLLAKUMQQDESIY
	LYPASSTSSTAPFENNFFNESMNECRNWQDNTAPMGNDTILKHEQIDQPQDVNSFAGGHPGLFQDSK
	NSDLYSIMKNLGIDFEDIRHMQNEKFFRNDFSGEVDFRDIDLTDEILTYVQDSLSKSPFIPSDYQQQ
	QSLALNSSCMVQEHLHLEQQQQHHQKQVVVEPQQQLCQKMXHMQVNGMFENWNSNQFVPFNCPQQDP
	QQYNVFTDLNGISQEFPYKSEMDSMPYTQNFISCNQPVLPQHSKCTELDYPMGSFEPSPYPTTSSLE
	DFVTCLQLPENQKHGLNPQSAIITPQTCYAGAVSMYQCQPEPQHTHVGQMQYNPvLPGQQAFLNKFQ
	NGVLNETYPAELNNINNTQTTTHLQPLHHPSEARPFPDLTSSGFL
	SEQ ID NO: 13	2677 bp
NOV2c,	CCAGTGCCCGGGGAGTAGCCGCCGCCGTCGGCTGGGCACCATGAACAGCAGCACCGCCAACATCACCT
CG105355-02
DNA Sequence	ACGCCAGTCGCAAGCGGCGGAAGCCGTGCAGAAAACAGTAAAGCCAATCCCAGCTGAAGGAAATCAAG
	TCAAATCCTTCCAAGCGGCATAGAGACCGACTTAATACACAGTTGGACCGTTTGGCTAGCCTGCTGCC
	TTTCCCACAAGATGTTATTAATAAGTTGGACAAACTTTCAGTTCTTAGGCTCAGCGTCAGTTACCTGA
	GAGCCAAGAGCTTCTTTGATGTTGCATTAAAATCCTCCCCTACTGAAAGAAACGGAGGCCAGGATAAC
	TGTAGAGCAGCAAATTTCAGAGAAGGCCTGAACTTACAAGAGGACAATTCTTATTACAGGCTCTGAAA
	TGGCTTTGTATTAGTTGTCACTACAGATGCTTTGGTCTTTTATGCTTCTTCTACTATACAAGATTATC
	TAGGGTTTCAGCAGTCTGATGTCATA&ATCAGAGTCTATATGAACTTATCCATACCGAAGACCGAGCT
	GAATTTCAOCGTCAGCTACACTGGGCATTAAATCCTTCTCAGTGTACAGAGTcTGGAcAAGGAATTGA
	AGAAGCCACTGGTCTCCCCCAGACAGTAGTCTGTTATAACCCAGACCAGATTCCTCCAGAAAACTCTC
	CTTTAATGGAGAGGTGCTTCATATGTCGTCTAWGTGTCTGCTGGATAATTCATCTGGTTTTCTAAACA
	ATGAATTTCCAAGGGAAGTTTAAAGTATCTTCATGGACAGAAGAAAGGGAGGATGGATCAAAAATACT
	TCCACCTCAGTTGGCTTTGTTTGCGATAGCTACTCCACTTCAGCCACCATCCATACTTGAAATCCGGA
	CCAAAAATTTTATCTTTAGAACCAAACACAAACTAGACTTCACACCTATTGGTTGTGATGCCAAAGGA
	AGAATTGTTTTAGGATATACTGAAGCAGAGCTGTGCACGAGAGGCTCAGGTTATCAGTTTATTCATGC
	AGCTGATATGCTTTATTGTGCCGACTCCCATATCCGAATGATTAAGACTGGAGAAAGTGGCATGATAG
	TTTTCCGGCTTCTTACAAAAAACAACCGATGGACTTGGGTCCAGTCTAATGCACGCCTGCTTTATAAA
	AATGGAAGACCAGATTATATCATTGTAACTCAGAGACCACTAACAGATGAGGAAGCAACAGAGCATTT
	ACGAAAACGAAATACGAAGTTGCCTTTTATGTTTACCACTGGAGAAGCTGTGTTGTATGAGGCAACCA
	ACCCTTTTCCTGCCATAATGGATCCCTTACCACTAAGGACTGAAAATGGCACTAGTGGAAAAGACTCT
	GCTACCACATCCACTCTAAGCAAGGACTCTCTCAATCCTAGTTCCCTCCTGGCTGCCATGATGCAACA
	AGATGAGTCTATTTATCTCTATCCTGCTTCAAGTACTTCAAGTACTGCACCTTTTGAAAACAACTTTT
	TCAACGAATCTATGAATGAATGCAGAAATTGGCAAGATAATACTGCACCGATGGGAAATGATACTATC
	CTGAAACATGAGCAAATTGACCAGCCTCAGGATGTGAACTCATTTGCTGGAGGTCACCCAGGGCTCTT
	TCAAGATAGTAAAAACAGTGACTTGTACAGCATAATGAAAAACCTAGGCATTGATTTTGAAGACATCA
	GACACATGCAGAATGAAAAATTTTTCAGAAATGATTTTTCTGGTGAGGTTGACTTCAGAGACATTGAC
	TTAACGGATGAAATCCTGACGTATGTCCAAGATTCTTTAAGTAAGTCTCCCTTCATACCTTCAGATTA
	TCAACAGCAACAGTCCTTGGCTCTGAACTCAAGCTGTATGGTACAGGAACACCTACATCTAGAACAGC
	AACAGCAACATCACCAAAAGCAAGTAGTAGTGGAGCCACAGCAACAGCTGTGTCAGAAGATGAAGCAC
	ATGCAAGTTAATGGCATGTTTGAAAATTGGAACTCTAACCAATTCGTGCCTTTCAATTGTCCACAGCA
	AGACCCACAACAATATAATGTCTTTACAGACTTACATGGGATCAGTCAAGAGTTCCCCTACAAATCTG
	AAATGGATTCTATGCCTTATACACAGAACTTTATTTCCTGTAATCAGCCTGTATTACCACAACATTCC
	AAATGTACAGAGCTGGACTACCCTATGGGGAGTTTTGAACCATCCCCATACCCCACTACTTCTACTTT
	AGAAGATTTTGTCACTTGTTTACAACTTCCTGAAAACCAAAAGCATGGATTAAATCCACAGTCAGCCA
	TAATAACTCCTCAGACATGTTATGCTGGGGCCGTGTCGATGTATCAGTGCCAGCCAGAACCTCAGCAC
	ACCCACGTGGGTCAGATGCAGTACAATCCAGTACTGCCAGGCCAACAGOCATTTTTAAACAAGTTTCA
	GAATGGAGTTTTAAATGAAACATATCCAGCTGAATTAAATAACATAAATAACACTCAGACTACCACAC
	ATCTTCAGCCACTTCATCATCCGTCAGAAGCCAGACCTTTTCCTGATTTGACATCCAGTGGATTCCTG
	TAATTCCAAGCCCAATTTTGAGCCTGGTTTTTGGATTAAATTAGTTTGTGAAGGATTATGGAAAAATA
	AAACTGTCACTGTTGGACGTCAGCA
	ORF Start: ATG at 41		ORF Stop: TAA at 2585
	SEQ ID NO: 14	848 aa	MW at 96146.5kD
NOV2c,	MNSSSANITYASRKRRKPVQKTVKPIPAEGIKSNPSKRHRDRLNTELDRLASLLPFPQDVINKLDKLS
CG105355-02
Protein	VLRLSVSYLRAKSFFDVALKSSPTERNGGQDNCRAANFREGLNLQEGEFLLQALNGFVLVVTTDALVF
Sequence
	YASSTIQDYLGFQQSDVIHQSVYELIHTEDRAEFQRQLHWALNPSQCTESGQGIEEATGLPQTVVCYN
	PDQIPPENSPLMERCFICRLRCLLDNSSGFLAMNFQGKLKYLHGQKKKGKDGSILPPQLALFAIATPL
	QPPSILEIRTKNFTERTKHKLDFTPIGCDAXGRIVLGYTEAELCTRGSGYQFHAADMLYCAESHITPL
	IKTGESGMIVFRLLTKNNRWTWVQSNARLLYKNGRPDYTIVTQRPLTDEEGTEHLRKRNTKLPFMFTT
	GEAVLYEATNPFPAIMDPLPLRTKNGTSGKDSATTSTLSKDSLNPSSLLAAMMQQDESIYLYPASSTS
	STAPFENNFFNESMNECRNWQDNTAPMGNDTILKHEQTDQPQDVNSFAGGHPGLFQDSKNSDLYSINK
	NLGIDFEDIRHMQNEKFFRNDFSGEVDFRDIDLTDEILTYVQDSLSKSPFIPSDYQQQQSLALNSSCM
	VQEMLHLEQQQQHHQKQVVVEPQQQLCQKMKHMQVNGMFENWNSNQFVPFNCFQQDPQQYNVFTDLHG
	ISQEFPYXSEMDSMPYTQNFISCNQPVLPQHSKCTELDYPMGSFEPSPYPTTSSLEDFVTCLQLPENQ
	KHGLNPQSAIITPQTCYAGAVSMYQCQPEPQHTHVGQMQYNPVLPGQQAFLNKFQNGVLNETYPAELN
	NINNTQTTTHLQPLHHPSEARPFPDLTSSGFL
	SEQ ID NO:15	2551 bp
NOV2d,	CACCATGAACAGCAGCAGCGCCAACATCACCTACGCCAGTCGCAAGCGGCGGAAGCCGGTGCAGAAA
CG105355-03
DNA Sequence	ACAGTAAAGCCAATCCCAGCTGAAGGAATCAAGTCAAATCCTTCCAAGCGGCATAGAGACCGACTTA
	ATACAGAGTTGGACCGTTTGGCTAGCCTGCTGCCTTTCCCACAAGATGTTATTAATAAGTTGGACAA
	ACTTTCAGTTCTTAGGCTCAGCGTCAGTTACCTGAGAGCCAAGAGCTTCTTTGATGTTGCATTAAAA
	TCCTCCCCTACTGAAAGAAACGGAGGCCAGGATAACTGTAGAGCAGCAAATTTCAGAGAAGGCCTGA
	ACTTACAAGAAGGAGAATTCTTATTACAGGCTCTGAATGGCTTTGTATTAGTTGTCACTACAGATGC
	TTTGGTCTTTTATGCTTCTTCTACTATACAAGATTATCTAGGGTTTCAGCAGTCTGATGTCATACAT
	CAGAGTGTATATGAACTTATCCATACCGAAGACCGAGCTGAATTTCAGCGTCAGCTACACTGGGCAT
	TAAATCCTTCTCAGTGTACAGAGTCTGGACAAGGAATTGAAGAAGCCACTGGTCTCCCCCAGACAGT
	AGTCTGTTATAACCCAGACCAGATTCCTCCAGAAAACTCTCCTTTAATGGAGAGGTGCTTCATATGT
	CGTCTAAGGTGTCTGCTGGATAATTCATCTGGTTTTCTCGCAATGAATTTCCAAGGGAAGTTAAAGT
	ATCTTCATGGACAGAAAAAGAAAGGGAAAGATGGATCAATACTTCCACCTCAGTTCGCTTTGTTTGC
	GATAGCTACTCCACTTCAGCCACCATCCATACTTGAAATCCCGACCAAAAATTTTATCTTTAGAACC
	AAACACAAACTAGACTTCACACCTATTGGTTGTGATGCCAAAGGAAGAATTGTTTTAGCATATACTG
	AAGCAGAGCTGTCCACGAGAGGCTCAGGTTATCAGTTTATTCATGCAGCTGATATGCTTTATTGTGC
	CGAGTCCCATATCCGAATGATTAAGACTGGAGAAAGTGGCATGATAGTTTTCCGGCTTCTTACAAAA
	AACAACCGATGGACTTGCGTCCAGTCTAATGCACGCCTGCTTTATAAAAATGGAAGACCAGATTATA
	TCATTGTAACTCAGAGACCACTAACAGATGAGGAAGGAACAGAGCATTTACGAAAACGAAATACGAA
	GTTGCCTTTTATGTTTACCACTGGAGAAGCTGTGTTGTATGAGGCAACCAACCCTTTTCCTGCCATA
	ATGGATCCCTTACCACTAAGGACTAAAAATGGCACTAGTCGAAAAGACTCTGCTACCACATCCACTC
	TAAGCAAGGACTCTCTCAATCCTAGTTCCCTCCTGGCTGCCATGATGCAACAAGATGAGTCTATTTA
	TCTCTATCCTGCTTCAAGTACTTCAAGTACTGCACCTTTTGAAAACAACTTTTTCAACGAATCTATG
	AATGAATGCAGAAATTGGCAAGATAATACTGCACCGATGGGAAATGATACTATCCTGAAACATGAGC
	AAATTGACCAGCCTCAGGATGTGAACTCATTTGCTGGAGGTCACCCAGGGCTCTTTCAAGATAGTAA
	AAACAGTGACTTGTACAGCATAATGAAAAACCTAGGCATTGATTTTGAAGACATCAGACACATGCAG
	AATGAAAAATTTTTCAGAAATGATTTTTCTGGTGAGGTTGACTTCAGAGACATTGACTTAACGGATG
	AAATCCTGACGTATGTCCAAGATTCTTTAAGTAAGTCTCCCTTCATACCTTCAGATTATCAACAGCA
	ACAGTCCTTGGCTCTGAACTCAAGCTGTATGGTACAGGAACACCTACATCTAGAACAGCAACAGCAA
	CATCACCAAAAGCAAGTAGTAGTGGAGCCACAGCAACAGCTGTGTCAGAAGATGAAGCACATGCAAG
	TTAATGGCATGTTTGAAAAGTGGAACTCTAACCAATTCGTGCCTTTCAATTGTCCACAGCAAGACCC
	ACAACAATATAATGTCTTTACAGACTTACATGGGATCAGTCAACAGTTCCCCTACAAATCTGAAGTG
	GATTCTATGCCTTATACACAGAACTTTATTTCCTGTAATCAGCCTGTATTACCACAACATTCCAAAT
	GTACAGAGCTGGACTACCCTATGGGGAGTTTTGAACCATCCCCATACCCCACTACTTCTAGTTTAGA
	AGATTTTGTCACTTGTTTACAACTTCCTGAAAACCAAAAGCATCGATTAAATCCACAGTCAGCCATA
	ATAACTCCTCAGACATGTTATGCTGGGGCCGTGTCGATGTATCAGTGCCAGCCAGAACCTCAGCACA
	CCCACGTGGGTCAGATGCAGTACAATCCAGTACTGCCAGGCCAACAGGCATTTTTAAACAAGTTTCA
	GAATGGAGTTTTAAATGAAACATATCCAGCTGAATTAAATAACATAAATAACACTCAGACTACCACA
	CATCTTCAGCCACTTCATCATCCGTCAGAAGCCAGACCTTTTCCTATTTGACATCCCAGTGGATTCC
	TGTAA
	ORF Start: at 2		ORF Stop: TAA at 2549
	SEQ ID NO: 16	849 aa	MW at 96247.6kD
NOV2d,	TMNSSSANITYASRKRRKPVQKTVKPIPAEGIKSNPSKRHRDRLNTELDRLASLLPFPQDVINKLDK
CG105355-03
Protein	LSVLRLSVSYLRAKSFFDVALKSSPTERNGGQDNCRAANFREGLNLQEGEPLLQALNGFVLVVTTDA
Sequence
	LVFYASSTIQDYLGFQQSDVIHQSVYELIHTEDRAEFQRQLHWALNPSQCTESGQGIEEATOLPQTV
	VCYMPDQIPPENSPLMERCFICRLRCLLDNSSGFLANNFQGKLKYLhGQKKKGKDGSILPPQLALFA
	IATPLQPPSILEIRDTKNFIFRTKHKLDFTPIGCDAKGRIVLGYTEAELCTRGSGYQFIHADMLYCA
	SHIRMIKTGESGMIVFRLLTKNNRWTWVQSNARLLYKNGRPDYIHIVTQRPLTDEEGTEHLRKRNTK
	LPFMFTTGEAVLYEATNPFPAIHDPLPLRTKNGTSGKDSATTSTLSKDSLNPSSLLAAMMQQDESIY
	LYPASSTSSTAPFENNFFNESNNECRNWQDNTAPMGNDTILKHEQIDQPQDVNSFAGGHPGLFQDSK
	NSDLYSIMKNLGIDFEDIRHMQNEKFFRNDFSGEVDFRDIDLTDEILTYVQDSLSKSPSIPSDYQQQ
	QSLLWSSCMVQEHLHLEQQQQHHQKQVVVEPQQQLCQKHTKHMQVNGMFENWNSNQFVPFNcPQQDP
	QQYNVFTDLHGISQEFPYKSEMDSMPYTQNFISCNQPVLPQHSKCTELDYPMGSFEPSPYPTTSSLE
	DFVTCLQLPENQKHGLNPQSAIITPQTCYAGAVSMYQCQPEPQHTHVGQMQYNPvLPGQQAFLNKFQ
	NGVLNETYPAELNNINNTQTTTHLQPLHHPSEARPFPDLTSSGFL

[0358] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 2B.

TABLE 2B
Comparison of NOV2a against NOV2b through NOV2d.
		NOV2a	Identities/
		Residues/	Similarities
	Protein	Match	for the
	Sequence	Residues	Matched Region
	NOV2b	1 . . . 848	783/848 (92%)
		2 . . . 849	783/848 (92%)
	NOV2c	1 . . . 848	783/848 (92%)
		1 . . . 848	783/848 (92%)
	NOV2d	1 . . . 848	783/848 (92%)
		2 . . . 849	783/848 (92%)

[0359] Further analysis of the NOV2a protein yielded the following properties shown in Table 2C.

TABLE 2C
Protein Sequence Properties NOV2a
PSort analysis:   0.5452 probability located in mitochondrial
                  matrix space; 0.4900 probability located in
                  nucleus; 0.3000 probability located in microbody
                  (peroxisome); 0.2672 probability located in
                  mitochondrial inner membrane
SignalP analysis: No Known Signal Sequence Predicted

[0360] search of the NOV2a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 2D.

TABLE 2D
Geneseq Results for NOV2a
		NOV2a	Identities/
		Residues/	Similarities
Geneseq	Protein/Organism/	Match	for the	Expect
Identifier	Length [Patent #, Date]	Residues	Matched Region	Value
AAW25668	Human Ah-receptor - Homo	1 . . . 848	847/848 (99%)	0.0
	sapiens, 848 aa.	1 . . . 848	847/848 (99%)
	[US5650283-A, 22 JUL. 1997]
AAR80551	Human Ah receptor protein -	1 . . . 848	847/848 (99%)	0.0
	Homo sapiens, 848 aa.	1 . . . 848	847/848 (99%)
	[US5378822-A, 03 JAN. 1995]
AAB73957	Guinea pig dioxin receptor -	1 . . . 848	661/852 (77%)	0.0
	Cavia porcellus, 846 aa.	1 . . . 846	734/852 (85%)
	[JP2000354494-A, 26 DEC. 2000]
AAR80561	Murine Ah receptor protein -	3 . . . 804	590/814 (72%)	0.0
	Mus musculus, 805 aa.	2 . . . 805	675/814 (82%)
	[US5378822-A, 03 JAN. 1995]
ABB08868	Cricetulus griseus dioxin	3 . . . 848	573/960 (59%)	0.0
	receptor SEQ ID NO 1 -	2 . . . 941	663/960 (68%)
	Cricetulus griseus, 941 aa.
	[JP2002045188-A, 12 FEB. 2002]

[0361] 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 2E.

TABLE 2E
Public BLASTP Results for NOV2a
		NOV2a	Identities/
Protein		Residues/	Similarities
Accession		Match	for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
P35869	Ah receptor (Aryl hydrocarbon	1 . . . 848	848/848 (100%)	0.0
	receptor) (AhR)- Homo	1 . . . 848	848/848 (100%)
	sapiens (Human), 848 aa.
Q95LD9	Aryl hydrocarbon receptor -	1 . . . 848	713/854 (83%)	0.0
	Delphinapterus leucas	1 . . . 845	767/854 (89%)
	(Beluga whale), 845 aa.
BAB88683	Aryl hydrocarbon receptor -	1 . . . 848	679/851 (79%)	0.0
	Phoca sibirica (Baikal seal),	1 . . . 843	740/851 (86%)
	843 aa.
O02747	AH receptor (Aryl hydrocarbon	1 . . . 848	669/852 (78%)	0.0
	receptor) - Oryctolagus cuniculus	1 . . . 847	734/852 (85%)
	(Rabbit), 847 aa.
Q95M15	Aryl hydrocarbon receptor -	1 . . . 848	676/851 (79%)	0.0
	Phoca vitulina (Harbor seal),	1 . . . 843	740/851 (86%)
	843 aa.

[0362] PFam analysis predicts that the NOV2a protein contains the domains shown in the Table 2F.

TABLE 2F
Domain Analysis of NOV2a
			Identities/
			Similarities for
	Pfam	NOV2a	the Matched	Expect
	Domain	Match Region	Region	Value
	PAS	113 . . . 177	20/69 (29%)	1.6e−13
			54/69 (78%)
	PAC	348 . . . 389	10/43 (23%)	1.3e−08
			37/43 (86%)

Example 3

[0363] The NOV3 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 3A.

TABLE 3A
NOV3 Sequence Analysis
	SEQ NO: 17	5221 bp
NOV3a,	ATAAAAGGGCGCTGAGGAAATACCGGACACGGTCACCCGTTGCCAGCTCTAGCCTTTAAATTCCCGGC
CG105521-01
DNA Sequence	TCGGGGACCTCCACGCACCGCGGCTAGCGCCGACAACCAGCTAGCGTGCAAGGCGCCGCGGCTCAGCG
	CGTACCGGCGGGCTTCGAAACCGCAGTCCTCCGGCGACCCCGAACTCCGCTCCGGAGCCTCAGCCCCC
	TGGAAAGTGATCCCGGCATCCGAGAGCCAAGATGCCGGCCCACTTGCTGCAGGACGATATCTCTAGCT
	CCTATACCACCACCACCACCATTACAGCGCCTCCCTCCAGGGTCCTGCAGAATGGAGGAGATAAGTTG
	GAGACGATGCCCCTCTACTTGGAAGACGACATTCGCCCTGATATAAAAGATGATATATATGACCCCAC
	CTACAAGGATAAGGAAGGCCCAAGCCCCAAGGTTGAATATGTCTGGAGAAACATCATCCTTATGTCTC
	TCCTACACTTGCGACCCCTGTATGGGATCACTTTGATTCCTACCTGCAAGTTCTACACCTGGCTTTGG
	GGGGTATTCTACTATTTTGTCAGTGCCCTGGGCATAACAGCAGGAGCTCATCGTCTGTGGAGCCACCG
	CTCTTACAAAGCTCGGCTGCCCCTACGGCTCTTTCTGATCATTGCCAACACAATGGCATTCCAGAATG
	ATGTCTATGAATGGGCTCGTGACCACCGTGCCCACCACAAGTTTTCAGAAACACATGCTGATCCTCAT
	AATTCCCGACGTGGCTTTTTCTTCTCTCACCTGGGTTGGCTCCTTGTGCGCAAACACCCAGCTGTCAA
	AGAGAAGCGGAGTACGCTACACTTGTCTGACCTAGAAGCTGAGAAACTGGTGATGTTCCAGAGGAGGT
	ACTACAAACCTGGCTTGCTGCTGATGTGCTTCATCCTCCCCACGCTTGTGCCCTGGTATTTCTGGGGT
	CAAACTTTTCAAAACAGTGTGTTCGTTGCCACTTTCTTGCGATATGCTCTCGTGCTTAATGCCACCTG
	GCTGGTGAACAGTGCTGCCCACCTCTTCGGATATCGTCCTTATGACAAGAACATTAGCCCCCGGGAGA
	ATATCCTGTTTTCACTTGGAGCTGTGGGTGACGGCTTCCACAACTACCACCACTCCTTTCCCTATGAC
	TACTCTGCCAGTGAGTACCGCTGGCACATCAACTTCACCACATTCTTCATTGATTGCATGGCCGCCCT
	CGGTCTGGCCTATGACCGGAAGAAAGTCTCCAAGGCCGCCATCTTGGCCAGGATTAAAAGAACCGGAG
	ATGCAAACTACAAGAGTCGCTGAGTTTGGGGTCCCTCAGGTTTCCTTTTTCAAAAACCAGCCACGCAG
	AGGTTTTAATGTCTGTTTATTAACTACTGAATAATGCTACCAGGATGCT~GATGATGATGTT~CC
	CATTCCAGTACAGTATTCTTTTAAAATTCAAAAGTATTGAAAGCCAAC~CTCTGCCTTTATGATGCT
	AAGCTGATATTATTTCTTCTCTTATCCTCTCTCTCTTCTAGGCCCATTGTCCTCCTTTTCACTTTATT
	GCTATCGCCCTCCTTTCCCTTATTGCCTCCCAGGCAAGCAGCTGGTCAGTCTTTGCTCAGTGTCCAGC
	TTCCAAAGCCTAGACAACCTTTCTGTAGCCTAAAACGAATGGTCTTTGCTCCAGATAACTCTCTTTCC
	TTGAGCTGTTGTGAGCTTTGAAGTAGGTGGCTTGAGCTAGAGATAAAACAGAATCTTCTGGGTAGTCC
	CCTGTTGATTATCTTCAGCCCAGGCTTTTGCTAGATGGA~ATGGAA~GC~CTTCATTTGACAC~G
	CTTCTAAGCAGGTAAATTGTCGGGGGAGAGAGTTAGCATGTATGAATGTAAGGATOAGG~AGCG~
	GCAAGAGGAACCTCTCGCCATGATCAGACATACAGCTGCCTACCTAATGAGGACTTC~GCCCCACCP
	CATAGCATGCTTCCTTTCTCTCCTGGCTCGGGGTAAAAAGTGGCTGCGGTCTTTGGC~TGCT~TTC
	AATCCCGCAACATATAGTTGAGGCCGAGGATAAAGAAAAGACATTTTAAGTTTGTAGT~~GTGGTC
	TCTGCTGGGGAAGGGTTTTCTTTTCTTTTTTTCTTTAATAACAAGGAGATTTCTTAGTTCATATATC~
	AGAAGTCTTGAAGTTGGGTGTTTCCAGAATTGGTAAAAACAGCAGCTCATGGAATTTTGAGTATTCCA
	TGAGCTGCTCATTACAGTTCTTTCCTCTTTCTGCTCTGCCATCTTCAGGATATTGGTTCTTCCCCTCA
	TAGTAATAAGATGGCTGTGGCATTTCCAAACATCCAAAAAAAGGGAAGGATTTAAGGAGGTGAAGTCG
	GGTCAAAAATAAAATATATATACATATATACATTGCTTAGAACGTTAAACTATTAGAGTATTTCCCTT
	CCAAAGAGGGATGTTTGGAAAAAACTCTGAAGGAGAGGAGAAATTAGTTCGGATGCCAATTTCCTCTC
	CACTGCTGGACATGAGATCGAGAGGCTGAGGGACAGGATCTATAGGCAGCTTCTAAGAGCGCACTTCA
	CATAGGAAGGGATCTGAGAACACGTTGCCAGGGGCTTGAGAAGGTTACTGAGTGAGTTATTGGGAGTC
	TTAATAAAATAAACTAGATATTAGGTCCATTCATTAATTAGTTCCAGTTTCTCCTTGAAATGAGTAAA
	AACTAGAAGGCTTCTCTCCACAGTGTTGTGCCCCTTCACTCATTTTTTTTTGAGGAGAAGGGGGTCTC
	TGTTAACATCTAGCCTAAAGTATACAACTGCCTGGGGGGCACGGTTAGGAATCTCTTCACTACCCTGA
	TTCTTGATTCCTGGCTCTACCCTGTCTGTCCCTTTTCTTTGACCAGATCTTTCTCTTCCCTGAGCGTT
	TTCTTCTTTCCCTGGACAGGCAGCCTCCTTTGTGTGTATTCAGAGGCAGTGATGACTTGCTGTCCAGT
	CAGCTCCCTPCCTGCACACAGAATGCTCAGGGTCACTGAACCACTGCTTCTCTTTTGAAAGTACAGCTA
	GCTGCCACTTTCACGTGGCCTCCGCAGTGTCTCCACCTACACCCCTGTGCTCCCCTGCCACACTGATC
	GCTCAAGACAAGGCTGGCAAACCCTCCCAGAAACATCTCTGGCCCAGAAAGCCTCTCTCTCCCTCCCT
	CTCTCATGAGGCACAGCCAAGCCAAGCGCTCATGTTGAGCCAGTGGGCCAGCCACAGAGCAAAAGAGG
	GTPTATTTTCAGTCCCCTCTCTCTGGGTCAGAACCAGAGGGCATGCTGAATGCCCCCTGCTTACTTGG
	TGAGGGTGCCCCGCCTGAGTCAGTGCTCTCAGCTGGCAGTGCAATGCTTGTAGTATATAGAAGTCTGG
	GTTCTCACTGGGAAGAAGCAAGGGCAAGAACCCAAGTGCCTCACCTCCAAAGGAGGCCCTGTTCCCTG
	GAGTCAGGGTGAACTGCAAGCTTTGGCTGAGACCTQGGATTTGAGATACCACAACCCTGCTGACATTT
	CAGTGTCTGTTCAGCAAACTAACCAGCATTCCCTACAGCCTAGGGCAGACAATAGTATAGAACTCTGC
	AAAAAAACAAAAACAGAATTTGAGAACCTTGGACCACTCCTGTCCCTGTAGCTCAGTCATCAAAGCAG
	AAGTCTCGCTTTGCTCTATTAAGATTGGAAATGTACACTACCAAACACTCAGTCCACTGTTGACCCCC
	AGTGCTGGAAGGGAGGAAGGCCTTTCTTCTGTGTTAATTGCGTAGAGGCTACAGGGGTTAGCCTGGAC
	TAAAGGCATCCTTGTCTTTTTGAGCTATTCACCTCAGTAGAAAAGGATCTAAGGGAGATCACTGTAGT
	TTAGTTCTGTTGACCTGTGCACCTACCCCTTGGAAATGTCTGCTGGTATTTCTAATTCCACAGGTCAT
	CAGATGCCTGCTTGATAATATATAAACAATAAAAACAACTTTCACTTCTTCCTATTGTAATCGTGTGC
	CATGGATCTGATCTGTACCATGACCCTACATAAGGCTGGATGGCACCTCAGGCTGAGGGCCCCAATGT
	ATGTGTGGCTGTGGGTGTGGGTGGGAGTGTGTCTGCTGAGTAAGGAACACGATTTTCAAGATTCTAAA
	GCTCAATTCAAGTGACACATTAATGATAAACTCAGATCTGATCAAGAGTCCGGATTTCTAACAGTCCC
	TGCTTTGGGGGGTGTGCTGACAACTTAGCTCAGGTGCCTTACATCTTTTCTAATCACAGTGTTGCATA
	TGAGCCTGCCCTCACTCCCTCTGCAGAATCCCTTTGCACCTGAGACCCTACTGAAGTAACTGGTAGAA
	AAAGGGGCCTGAGTGGAGGATTATCAGTATCACGATTTGCAGGATTCCCTTCTGGGCTTCATTCTGGA
	AACTTTTGTTAGGGCTGCTTTTCTTAAGTGCCCACATTTGATGGAGGGTGGAAATAATTTGAATGTAT
	TTGATTTATAAGTTTTTTTTTTTTTTTGGGTTAAAAGATGGTTGTAGCATTTAAAATGGAAAATTTTC
	TCCTTGGTTTGCTAGTATCTTGGGTGTATTCTCTGTAAGTGTAGCTCAAATACGTCATCATGAGGTAA
	TAAAAAAGCGAGGTGGCCATGTTATGCTGGTGGTTAAGGCCAGACCTCTCCACCACTGTGCCACTCAA
	ACTTGCTGTGTGACCCTGGGCAAGTCACTTAACTATAAGGTGCCTCAGTTTTCCTTCTGTTAAAATGG
	GGATAATAATACTGACCTACCTCAAAGGGCAGTTTTGAGGCATGACTAATGCTTTTTAGAAAGCATTT
	TGGGATCCTTCAGCACAGGAATTCTCAAGACCTGAGTATTTTTTATAATAGGAATGTCCACCATGAAC
	TTGATACGTCCGTGTGTCCCAGATGCTGTCATTAGTCTATATGGTTCTCCAAGAAACTGAATGAATCC
	ATTGGAGAAGCGGTGGATAACTAGCCAGACAAAATTTGAGAATACATAAACAACGCATTGCCACGGAA
	ACATACAGAGGATGCCTTTTCTGTGATTGGGTGGGATTTTTTCCCTTTTTATGTGGGATATAGTAGTT
	ACTTGTGACAAAAATAATTTTGGAATAATTTCTATTAATATCAACTCTGAAGCTAATTGTACTAATCT
	GAGATTGTGTTTGTTCATAATAAAAGTGAAGTGAATCTAAAAAAAAAAAAAAA
	ORF Start: ATG at 236		ORF Stop: TGA at 1313
	SEQ ID NO:18	359 aa	MW at 41504.1kD
NOV3a,	MPAHLLQDDISSSYTTTTTITAPPSRVLQNGGDKLETMPLYLEDDIRPDIKDDIYDPTYKDKEGPSPK
CG105521-01
Protein	VEYVWRNIILMSLLHLGALYGITLIPTCKFYTWLWGVFYYFVSALGITAGAHRLWSHRSYKARLPLRL
Sequence
	FLIIANTMAFQNDVYEWARDHRAHHKFSETHADPHNSRRGFFFSHVGWLLVRKHPAVKEKGSTLDLSD
	LEAEKLVMFQRRYYKPGLLLMCFILPTLVPWYFWGETFQNSVFVATFLRYAVVLNATWLVNSAAHLFG
	YRPYDKNISPRENTLVSLGAVGEGFHNYHHSFPYDYSASEYRWHIMFTTFFIDCMAALGLAYDRKKVS
	SEQ ID NO: 19	1988 bp
NOV3b,	GGGCTGAGCAAATACCGGACACGCTCACCCGTTGCCAGCTCTAGCCTTTAAATTCCCGGCTCGGGG
CG105521-02
DNA Sequence	ACCTCCACGCACCGCGGCTAGCGCCGACAACCAGCTAGCGTGCCAACGCCGCGGCTCAGCGCGTAC
	CGCCGGGCTTCGAAACCGCAGTCCTCCGGCGACCCCGAACTCCGCTCCGGAGCCTCAGCCCCTGGA
	AAGTGATCCCGGCATCCGAGAGCCAAGATGCCGGCCCACTTGCTGCAGGCGATATCTCTAGCTCCT
	ATACCACCACCACCACCATTACAGCGCCTCCCTCCAGGTCCTGCAGAATGGAGGAGATAAGTTTGGA
	GACGATGCCCCTCTACTTGGAAGACGACATTCGCCCTGATATAAAAGATGATATATATGACCCCACC
	TACAAGGATAAGGAAGGCCCAAGCCCCAAGGTTGAATATGTCTGGAGAAACATCATCCTTATGTCTC
	TGCTACACTTGGGAGCCCTGTATGGGATCACTTTGATTCCTACCTGCAAGTTCTACACCTGGCTTTG
	GGGGGTATTCTACTATTTTGTCAGTGCCCTGGGCATAACAGCAGGAGCTCATCGTCTGTGGAGCCAC
	CGCTCTTACAAGCTCGGCTGCCCCTACCGCTCTTTCTGATCATTGCCAACACAATGGCATTCCAGAA
	ATGATGTCTATGAATGGGCTCGTGACCACCGTGCCCACCACAAGTTTTCAGAAACACATGCTGATCC
	TCATAATTCCCGACGTGGCTTTTTCTTCTCTCACGTGGGTTGGCTGCTTGTGCCCAAACACCCAGCT
	GTCAAAGAGAAGGGGAGTACGCTAGACTTGTCTGACCTAGAAGCTGAGAAACTGGTGATGTTCCAGA
	GGAGGTACTACAAACCTGGCTTGCTGATGATGTCCTTCATCCTGCCCACGCTTGTGCCCTAATATTT
	CTGGGGTGAAACTTTTCAAAACAGTGTGTTCGTTGCCACTTTCTTGCGATATGCTGTGGTGCTTAAT
	GCCACCTGGCTGGTGAACAGTGCTGCCCACCTCTTCGGATATCGTCCTTATGACAAGAACATTAGCC
	CCCGGGAGAATATCCTGGTTTCACTTGGAGCTGTGGGTGAGGGCTTCCACAACTACCACCACTCCTT
	TCCCTATGACTACTCTGCCAGTGAGTACCGCTGGCACATCAACTTCACCACATTCTTCATTGATTGC
	ATGGCCGCCCTCGGTCTGGCCTATGACCGGAAGAAAGTCTCCAACGCCGCCATCTTGGCCAGGATTA
	AAAGAACCGGAGATGGAAACTACAAGAGTGGCTGAGTTTGGGGTCCCTCAGGTTCCTTTTTCAAAAA
	CCAGCCAGGCAGAGGTTTTAATGTCTGTTTATTAACTACTGAATAATGCTACCAGGATGCTAAAGAT
	GATGATGTTAACCCATTCCAGTACACTATTCTTTTAAAATTCAAAAGTATTGAAAGCCAACAACTCT
	GCCTTTATGATGCTAAGCTGATATTATTTCTTCTCTTATCCTCTCTCTCTTCTAGGCCCATTGTCCT
	CCTTTTCACTTTATTGCTATCGCCCTCCTTTCCCTTATTGCCTCCCACGCAAGCAGCTGGTCAGTCT
	TTGCTCAGTGTCCAGCTTCCAAGCCTAGACAACCTTTCTGTAGCCTAAAACGAATTGGTCTTTGCTC
	CAGATAACTCTCTTTCCTTGAGCTGTTGTGAGCTTTGAAGTAGGTGGCTTGAGCTAGAGATAAAACA
	GAATCTTCTGGGTAGTCCCCTGTTGATTATCTTCAGCCCAGGCTTTTGCTAGATGGAATGGAAAAGC
	AACTTCATTTGACACAAAGCTTCTAAAGCAGGTAAATTGTCGGGGGAGAGAGTTAGCATGTATGAAT
	GTAAGGATGAGGGAAGCGAAGCAACAGGAACCTCTCGCCATGATCAGACATACAGCTGCCTACCTAA
	TGAGGACTTCAAGCCCCACCACATAGCATGCTTCCTTTCTCTCCT
	ORF Start: ATG at 229		ORF Stop: TGA at 1306
	SEQ ID NO:20	359 aa	MW at 41522.2kD
NOV3b,	MPAHLLQDDISSSYTTTTTITAPPSRVLQNGGDKLETMPLYLEDDIRPDIKDDIYDPTYKDKEGPSP
CG105521-02
Protein	KVEYVWRNIILMSLLHLGALYGITLIPTCKFYTWLWGVFYYFVSALGITAGAHRLWSHRSYKARLPL
Sequence
	RLFLIIANTMAFQNDVYEWARDHRAHHKFSETHADPHNSRRGFFFSHVGWLLVRKHPAVKEKGSTLD
	LSDLEAEKLVMFQRRYYKPGLLMMCFILPTLVPWYFWGETFQNSVFVATFLRYAVVLNATWLVNSAA
	HLFGYRPYDKNISPRENILVSLGAVGEGFHNYHHSFPYDYSASEYRWHINFTTFFIDCMAALGLAYD
	RKKVSKAAILARIKRTGDGNYKSG
	SEQ ID NO:21	1104 bp
NOV3c,	CACCGGATCCACCATGCCGGCCCACTTGCTGCAGGACGATATCTCTAGCTCCTATACCACCACCACCA
301113881
DNA Sequence	CCATTACAGCGCCTCCCTCCAGGGTCCTGCAGAATGGAGGAGATAAGTTGGAGACGATGCCCCTCTAC
	TTGGAAGACGACATTCGCCCTGATATAAAAGATGATATATATGACCCCACCTACAAGGATAAGGAAGG
	CCCAAGCCCCAAGGTTGAATATGTCTGGAGAAACATCATCCTTATGTCTCTGCTACACTTAGAGACCC
	TGTATGGGATCACTTTGATTCCTACCTGCAAGTTCTACACCTGGCTTTGGGGAATATTCTACTATTTT
	GTCAGTGCCCTGGGCATAACAGCAGGAGCTCATCGTCTGTGGAGCCACCGCTCTTACAAAGCTCGGCT
	GCCCCTACGGCTCTTTCTGATCATTGCCAACACAATGGCATTCCAGAATGATGTCTATGAATGGGCTC
	GTGACCACCGTGCCCACCACAAGTTTTCAGAAACACATGCTGATCCTCATAATTCCCGACGTGGCTTT
	TTCTTCTCTCACGTGGGTTGGCTGCTTGTGCGCAAACACCCAGCTGTCAAAGAGAAGGGGAGTACGCT
	AGACTTGTCTGACCTAGAAGCTGAGAAACTGGTGATGTTCCAGAGGAGGTACTACAAACCTAACTTGC
	TGATGATGTGCTTCATCCTGCCCACGCTTGTGCCCTGGTATTTCTGGGGTGAAACTTTTCAAAACAGT
	GTGTTCGTTGCCACTTTCTTGCGATATGCTGTGGTGCTTAATGCCACCTGGCTGGTGAACAGTGCTGC
	CCACCTCTTCGGATATCGTCCTTATGACAAGAACATTAGCCCCCAAGAGAATATCCTGGTTTCACTTG
	GAGCTGTGGGTGAGGGCTTCCACAACTACCACCACTCCTTTCCCTATGACTACTCTGCCAGTGAGTAC
	CGCTGGCACATCAACTTCACCACATTCTTCATTGATTGCATGGCCGCCCTCGGTCTGGCCTATGACCG
	GAAGAAAGTCTCCAAGGCCGCCATCTTGGCCAGGATTAAAAGAACCGGAGATGGAACTACAAACAGTG
	GCTGAGCGGCCGCTAT
	ORF Start: at 2		ORF Stop: TGA at 1091
	SEQ ID NO: 22	363 aa	MW at 41868.5kD
NOV3c,	TGSTMPAHLLQDDISSSYTTTTTTTAPPSRVLQNGGDKLETMPLYLEDDIRPDIKDDIYDPTYKDKEG
301113881
Protein	PSPKVEYVWRNIILMSLLHLGALYGITLIPTCKFYTWLWGVFYYFVSALGITAGARRLWSHRSYKARL
Sequence
	PLRLFLIIANTMAFQNDVYEWARDHRAHHKFSETHADPHNSRRGFFFSHVGWLLVRKHPAVKEKGSTL
	DLSDLEAEKLVMFQRRYYKPGLLMMCFILPTLVPWYFWGETFQNSVFVATFLRYAVVLNATWLVNSAA
	ELFGYRPYDKNISPRENILVSLGAVGEGFHYHHSFPYDYSASEYRWHINFTTFFIDCMAAKLGLAYDR
	KKVSKAAILARIKRTGDGNYKSG
	SEQ ID NO:23	5221 bp
NOV3d,	ATAAAAGGGGGCTGACGAATACCGGACACGGTCACCCGTTGCCAGCTCTAGCCTTTTAAATTCCCGG
CG105521-01
DNA Sequence	CTCGGGGACCTCCACGCACCGCGGCTAGCGCCGACAACCAGCTAGCGTCCAAGGCGCCGCGGCTCAG
	CGCGTACCGGCGGGCTTCGAAACCGCAGTCCTCCGGCGACCCCGAACTCCGCTCCGGAGCCTCAGCC
	CCCTGGAAAGTGATCCCGGCATCCGAGAGCCAAGATGCCGGCCCACTTGCTGCAGGACGATATCTCT
	AGCTCCTATACCACCACCACCACCATTACAGCGCCTCCCTCCAGGGTCCTGCAGAATAAAGGAGATA
	AGTTGGAGACGATGCCCCTCTACTTGGAAGACGACATTCGCCCTGATATAAAAGATGATATATATGA
	CCCCACCTACAAGGATAAGGAAGGCCCAAGCCCCAAGGTTGAATATGTCTGGAGAAACATCATCCTT
	ATGTCTCTGCTACACTTGGGAGCCCTGTATGGGATCACTTTGATTCCTACCTGCAAGTTCTACACCT
	GGCTTTGGGGGGTATTCTACTATTTTGTCAGTGCCCTGGGCATAACAGCAGGAGCTCATCGTCTGTG
	GAGCCACCGCTCTTACAAGCTCGGCTGCCCCTACGGCTCTTTCTGATCATTGCCAAACACAATGGCA
	TTCCAGAATGATGTCTATGAATGGGCTCGTGACCACCGTGCCCACCACAAGTTTTCAGAAACACATG
	CTGATCCTCATAATTCCCGACGTGGCTTTTTCTTCTCTCACGTGGGTTGGCTGCTTGTGCGCAAACA
	CCCAGCTGTCAAAGAGAAGCGGAGTACGCTAGACTTGTCTGACCTAGAAGCTGAGAAACTGGTGATG
	TTCCAGAGGAGGTACTACAAACCTGGCTTGCTGCTGATGTGCTTCATCCTGCCCACGCTTGTGCCCT
	GGTATTTCTGGGGTGAAACTTTTCAAAACAGTGTGTTCGTTGCCACTTTCTTGCGATATGCTGTGGT
	GCTTATGCCACCTGGCTGGTGACAGTGCTGCCCACCTCTTCGGATATCGTCCTTATGACAAGAAGCC
	ATTAGCCCCCGGGAGAATATCCTGGTTTCACTTGGAGCTGTGGGTGAGGGCTTCCACAACTACCACC
	ACTCCTTTCCCTATGACTACTCTGCCAGTGACTACCGCTGCCACATCAACTTCACCACATTCTTCAT
	TGATTGCATGGCCGCCCTCGGTCTGGCCTATGACCGGAAGAAAGTCTCCAAGGCCGCCATCTTGGCC
	AGGATTAAAAGAACCGGAGATGGAAACTACAAGAGTGGCTGAGTTTGGGGTCCCTCAGGTTTCCTTT
	TTCAAAAACCAGCCAGGCAGAGGTTTTAATGTCTGTTTATTAACTACTGAATAATGCTACCAGGATG
	CTAAAGATGATGATGTTAACCCATTCCAGTACAGTATTCTTTTAAAATTCAAAAGTATTGAAAGCCA
	ACAACTCTGCCTTTATGATGCTAACCTGATATTATTTCTTCTCTTATCCTCTCTCTCTTCTAGGCCC
	ATTGTCCTCCTTTTCACTTTATTGCTATCGCCCTCCTTTCCCTTATTGCCTCCCAGGCAAGCAGCTG
	GTCAGTCTTTGCTCAGTGTCCAGCTTCCAAAGCCTAGACAACCTTTCTGTAGCCTAAAACGAATGGT
	CTTTGCTCCAGATAACTCTCTTTCCTTGAGCTGTTGTGAGCTTTGAAGTAGGTGGCTTGAGCTAGAG
	ATAAAACAGAATCTTCTGGGTAGTCCCCTGTTGATTATCTTCAGCCCAGGCTTTTGCTAGATGGAAT
	GGAAAAGCAACTTCATTTGACACAAAGCTTCTAAAGCAGGTAAATTGTCGGGGGAGAGAGTTAGCAT
	GTATGAATGTAAGGATGAGGGAAGCGAAGCAAGAGGAACCTCTCGCCATGATCAGACATACAGCTCC
	CTACCTAATGAGGACTTCAAGCCCCACCACATAGCATGCTTCCTTTCTCTCCTGGCTCGGGGTAAAA
	AGTGGCTGCGGTGTTTGGCAATGCTAATTCAATGCCGCAACATATAGTTGAGGCCGAGGATAAAGAA
	AAGACATTTTAAGTTTGTAGTAAAAGTGGTCTCTGCTGGGGAAGGGTTTTCTTTTCTTTTTTTCTTT
	AATAACAAGGAGATTTCTTAGTTCATATATCAAGAAGTCTTGAAGTTGGGTGTTTCCAGAATTGGTA
	AAAACAGCAACTCATGGAATTTTGAGTATTCCATGAGCTGCTCATTACAGTTCTTTCCTCTTTCTGC
	TCTGCCATCTTCAGGATATTGGTTCTTCCCCTCATAGTAATAAGATGGCTGTGGCATTTCCAAACAT
	CCAAAAAAAGGGAAGGATTTAAGGAGGTGAAGTCGGGTCAAAAATAAAATATATATACATATATACA
	TTGCTTAGAACGTTAAACTATTAGAGTATTTCCCTTCCAAAGACGGATGTTTGGAAAAAACTCTGAA
	AGAGAGGAGGAATTAGTTGGGATGCCAATTTCCTCTCCACTGCTGGACATGAGATGGAGAGGCTGAG
	GGACAGGATCTATAGGCAGCTTCTAAGAGCGAACTTCACATAGGAAGGGATCTGAGAACACGTTGCC
	AGGGGCTTGAGAAGGTTACTGAGTGAGTTATTGGGAGTCTTAATAAAATAAACTAGATATThGGTCC
	ATTCATTAATTAGTTCCAGTTTCTCCTTGAAATGAGTAAAAACTAGAACGCTTCTCTCCACAGTGTT
	GTGCCCCTTCACTCATTTTTTTTTGAGGAGAAGCGGGTCTCTGTTAACATCTAGCCTAAAGTATACA
	ACTGCCTGGGGGGCAGGGTTACGAATCTCTTCACTACCCTGATTCTTCATTCCTGGCTCTACCCTGT
	CTGTCCCTTTTCTTTGACCAGATCTTTCTCTTCCCTGAACGTTTTCTTCTTTCCCTGGACAGGCAGC
	CTCCTTTGTGTGTATTCAGAGGCAGTGATGACTTGCTGTCCAGGCAGCTCCCTCCTGCACACAGAAT
	GCTCAGGGTCACTGAACCACTGCTTCTCTTTTGAAAGTAGAGCTAGCTGCCACTTTCACGTGCCCTC
	CGCAGTGTCTCCACCTACACCCCTGTGCTCCCCTGCCACACTGATGGCTCAAGACAAGGCTGGCAAA
	CCCTCCCAGAAACATCTCTGGCCCAGAAAGCCTCTCTCTCCCTCCCTCTCTCATGAGGCACAGCCAA
	GCCAAGCGCTCATGTTGAGCCAGTGGGCCAGCCACAGAGCAAAAGAGGGTTTATTTTCAGTCCCCTC
	TCTCTGGGTCAGAACCAGAGGGCATGCTGAATGCCCCCTGCTTACTTGGTGAGGGTGCCCCGCCTGA
	GTCAGTGCTCTCAGCTGGCAGTGCAATGCTTGTAGAAGTACGAGGAAACAGTTCTCACTGGGAAGAA
	GCAACGGCAAGAACCCAAGTGCCTCACCTCGAAAGGAGGCCCTGTTCCCTGGAGTCAGCGTGAACTG
	CAAAGCTTTGGCTGACACCTGGGATTTGAGATACCACAAACCCTGCTGAACACAGTGTCTGTTCAGC
	AAACTAACCAGCATTCCCTACAGCCTAGGGCAGACAATAGTATAGAAGTCTGGAAAAAAACAAAAAC
	AGAATTTGAGAACCTTGGACCACTCCTGTCCCTGTAGCTCAGTCATCAAAGCAGAAGTCTGGCTTTG
	CTCTATTAAGATTGGAAATGTACACTACCAAACACTCAGTCCACTGTTGAGCCCCAGTGCTCGAAGG
	GAGGAAGGCCTTTCTTCTGTGTTAATTGCGTAGAGGCTACAGGGGTTAGCCTGGACTAAAGGCATCC
	TTGTCTTTTGAGCTATTCACCTCAGTAGAAAAGGATCTAAGGGAAGATCACTGTAGTTTAGTTCTGT
	TGACCTGTGCACCTACCCCTTGGAAATGTCTGCTGGTATTTCTAATTCCACAGGTCATCAGATGCCT
	CCTTGATAATATATAAACAATAAAAACAACTTTCACTTCTTCCTATTGTAATCGTGTGCCATGGATC
	TGATCTGTACCATGACCCTACATAAGGCTGGATGGCACCTCAGGCTGAGCGCCCCAATGTATGTGTG
	GCTGTGGGTGTGGGTGGGAGTGTGTCTGCTGAGTAAGGAACACGATTTTCAAGATTCTAAAGCTCAA
	TTCAAGTGACACATTAATGATAAACTCAGATCTGATCAAGAGTCCGGATTTCTAACAGTCCCTGCTT
	TGGGGGGTGTGCTGACAACTTAGCTCAGGTGCCTTACATCTTTTCTAATCACAGTGTTGCATATGAG
	CTCTGCCTCACTCCCTCTGCAGAATCCCTTTGCACCTGAGACCCTACTGAAGTGGCTGGTAGAAAAA
	GGGGCCTGAGTGGAGGATTATCAGTATCACGATTTGCAGGATTCCCTTCTGGGCTTCATTCTGGAAA
	CTTTTGTTAGGGCTGCTTTTCTTAAGTGCCCACATTTGATGGAGGGTGGAAATAATTTGAATGTATT
	TGATTTATAAGTTTTTTTTTTTTTTTGGGTTAAAAGATGGTTGTAGCATTTAAAATGGAAAATTTTC
	TCCTTGGTTTGCTAGTATCTTGGGTTTATTCTCTGTAAGTGTAGCTCAAATAGGTCATCATGAAAGG
	TTAAAAAAGCGAGGTGGCCATGTTATGCTGGTGGTTAAGGCCAGGGCCTCTCCAACCACTGTGCCAC
	TGACTTGCTGTGTGACCCTGGGCAAGTCACTTAACTATAAGGTGCCTCAGTTTTCCTTCTGTTAAAA
	TGGGGATAATAATACTGACCTACCTCAAAGGGCAGTTTTGAGGCATGACTAATGCTTTTTAGAAAGC
	ATTTTGCGATCCTTCAGCACAGGAATTCTCAAGACCTGAGTATTTTTTATAATAGGAATGTCCACCA
	TGAACTTGATACGTCCGTGTGTCCCAGATGCTGTCATTAGTCTATATGGTTCTCCAAGAAACTGAAT
	GAATCCATTGGAGAAGCCGTGGATAACTAGCCAGACAAAATTTGACAATACATAAACAACGCATTGC
	TACGGAAACATACAGAGGATGCCTTTTCTGTGATTGGGTGGGATTTTTTCCCTTTTTATGTGGGATA
	TAGTAGTTACTTGTGACAAAAATAATTTTGGAATAATTTCTATTAATATCAACTCTGAAGCTAATTG
	TACTAATCTGAGATTGTGTTTGTTCATAATAAAAGTGAAGTGAATCTAAAAAAAAAAAAAAA
	ORF Start: ATG at 236		ORF Stop: TGA at 1313
	SEQ ID NO: 24	359 aa	MW at 41504.1kD
NOV3d,	MPAHLLQDDISSSYTTTTTITAPPSRVLQNGGDKLETMPLYLEDDIRPDIKDDIYDPTYKDKEGPSP
CG105521-01
Protein	KVEYVWRNIILMSLLHLGALYGITLTPTCKFYTWLWGVFYYFVSALGITAGAHRLWSHRSYKARLPL
Sequence
	RLFLIIANTMAFQNDVYEWARDHRAHHKFSETHADPHNSRRGFFFSHVGWLLVRKHPAVKEKGSTLD
	LSDLEAEKLVMFQRRYYXPGLLLMCFILPTLVPWYFWGETFQNSVFVATFLRYAVVLNATWLVNSAA
	HLFGYRPYDKNISPRENILVSLGAVGEGFHNYHHSFPYDYSASEYRWUINFTTFFIDCMAALGLAYD
	RKKVSKAAILARIKRTGDGNYKSG
	SEQ ID NO:25	1116 bp
NOV3e,	CCGGCCCACTTGCTGCAGGACGATATCTCTAGCTCCTATACCACCACCACCACCATTACAGCGCCTCC
309330043
DNA Sequence	CTCCAGGGTCCTGCAGAATGGAGGAGATAAGTTGGAGACCATGCCCCTCTACTTGCAAGACGACATTC
	GCCCTGATATAAAAGATGATATATATGACCCCACCTACAAGGATAACGAAGGCCCAAGCCCCAAGGTT
	GAATATGTCTGGAGAAACATCATCCTTATGTCTCTGCTACACTTGGGAGCCCTGTATGGGATCACTTT
	GATTCCTACCTGCAAGTTCTACACCTGGCTTTGGGGGGTATTCTACTATTTTGTCAGTGCCCTGGCCA
	TAACAGCAGGAGCTCATCGTCTGTGGAGCCACCGCTCTTACAAAGCTCGGCTGCCCCTACGGCTCTTT
	CTCATCATTGCCAACACAATGGCATTCCAGAATGATGTCTATGAATGGGCTCGTGACCACCGTGCCCA
	CCACAAGTTTTCAGAAACACATGCTGATCCTCATAATTCCCGACGTGGCTTTTTCTTCTCTCACGTGG
	GTTGCCTGCTTGTGCGCAAACACCCAGCTGTCAAAGAGAAGGGGAGTACGCTAGACTTGTCTGACCTA
	GAAGCTGAGAAACTGGTGATGTTCCAGAGGAGGTACTACAAACCTG~CTTGCTGATGATGTGCTTCAT
	CCTGCCCACGCTTGTGCCCTGGTATTTCTGGGGTGAAACTTTTCAAAACAGTGTGTTCGTTGCCACTT
	TCTTGCGATATGCTGTGGTGCTTAATGCCACCTGGCTGGTGAACAGTGCTGCCCACCTCTTCGGATAT
	CGTCCTTATGACAAGAACATTAGCCCCCGGGAGAATATCCTGGTTTCACTTGGAGCTGTGGGTGAGGG
	CTTCCACAACTACCACCACTCCTTTCCCTATGACTACTCTGCCAGTGAGTACCGCTGGCACATCAACT
	TCACCACATTCTTCATTGATTGCATGGCCGCCCTCGGTCTGGCCTATGACCGGAAGAAAGTCTCCAAG
	GCCGCCATCTTGGCCAGGATTAAAAGAACCGGAGATGGAAACTACAAGAGTGGCTGAGCAGGTGCGGC
	CGCACTCGAGCACCACCACCACCACCAC
	ORF Start: at 1		ORF Stop: TGA at 1075
	SEQ ID NO:26	358 aa	MW at 41391.0kD
NOV3e,	PAHLLQDDISSSYTTTTTITAPPSRVLQNGGDKLETMPLYLEDDIRPDIKDDIYDPTYKDKEGPSPKV
309330043
Protein	EYVWRNIILMSLLHLGALYGITLIPTCKFYTWLWGVFYYFVSALGITAGAHRLWSHRSYKARLPLRLF
Sequence
	LIIANTMAFQNDVYEWARDHRAHHKFSETHADPHNSRRGFFESHVCWLLVRKHPAVKEKGSTLDLSDL
	EAEKLVMFQRRYYKPGLLMMCFILPTLVPWYFWGETFQNSVFVATFLRYAVVLNATWLVNSAAHLFGY
	RPYDKNISPRENILVSLGAVGEGFHNYHHSFPYDYSASEYRWHINFTTFFIDCMAALGLAYDRKKVSK
	AAILARIKRTGDGNYKSG
	SEQ ID NO:27	1129 bp
NOV3f,	ACATCATCACCACCATCACCCGGCCCACTTGCTGCAGGACGATATCTCTAGCTCCTATACCACCACCA
309330069
DNA Sequence	CCACCATTACAGCGCCTCCCTCCAGGGTCCTGCAGAATGGAGGAGATAAGTTGGAGACGATGCCCCTC
	TACTTGGAAGACGACATTCGCCCTGATATAAAAGATGATATATATGACCCCACCTACAAGGATAAGGA
	ACGCCCAAGCCCCAAGGTTGAATATGTCTGGAGAAACATCATCCTTATGTCTCTGCTACACTTGGGAG
	CCCTGTATGGGATCACTTTGATTCCTACCTGCAAGTTCTACACCTGGCTTTGGGGGGTATTCTACTAT
	TTTGTCAGTGCCCTGGGCATAACAGCACGAGCTCATCGTCTGTGGAGCCACCGCTCTTACAAAGCTCG
	GCTGCCCCTACGGCTCTTTCTGATCATTGCCAACACAATGGCATTCCAGAATGATGTCTATGAATGGG
	CTCGTGACCACCGTGCCCACCACAAGTTTTCAGAAACACATGCTGATCCTCATAATTCCCGACGTGGC
	TTTTTCTTCTCTCACGTGGGTTGGCTGCTTGTGCGCAAACACCCAGCTGTCAAAGAGAAGGGGAGTAC
	GCTAGACTTGTCTGACCTAGAAGCTGAGAAACTCGTGATGTTCCAGAGGACGTACTACAAACCTGGCT
	TGCTGATGATGTGCTTCATCCTGCCCACGCTTGTGCCCTGGTATTTCTGGGGTGAAACTTTTCAAAAC
	AGTGTGTTCGTTGCCACTTTCTTGCGATATGCTGTGGTGCTTAATGCCACCTGCCTGGTGAACAGTGC
	TGCCCACCTCTTCGGATATCGTCCTTATGACAAGAACATTAGCCCCCGGGAGAATATCCTGGTTTCAC
	TTGGAGCTGTGGGTGAGGGCTTCCACAACTACCACCACTCCTTTCCCTATGACTACTCTGCCAGTGAG
	TACCGCTGGCACATCAACTTCACCACATTCTTCATTGATTGCATGGCCGCCCTCGOTCTGGCCTATGA
	CCGGAAGAAAGTCTCCAAGGCCGCCATCTTGGCCAGGATTAAAAGAACCGGAGATGGAAACTACAAGA
	GTGGCTGAGCGGCCGCACTCGAGCACCACCACCACCACCAC
	ORF Start: at 2		ORF Stop: TGA at 1094
	SEQ ID NO: 28	364 aa	MW at 42213.9kD
NOV3f,	HHHHHHPAHLLQDDISSSYTTTTTITAPPSRVLQNGGDKLETMPLYLEDDIRPDIKDDIYDPTYKDKE
309330069
Protein	GPSPKVEYVWRNIILMSLLHLGALYGITLIPTCKFYTWLWGVFYYFVSALGITAOAHRLWSHRSYKAR
Sequence
	LPLRLFLIIANTMAFQNDVYEWARDHRAHHKFSETHADPHNSRRGFFFSHVGWLLVRKHPAVKEKGST
	LDLSDLEAEKLVMFQRRYYKPGLLMMCFILPTLVPWYFWGETFQNSVFVATFLRYAVVLNATWLVNSA
	AHLFGYRPYDKNISPRENTLVSLGAVGEOFHNYHHSFPYDYSASEYRWHINFTTFEIDCHAALGLAYD
	RKKVSKAAILARIKRTGDGNYKSG
	SEQ ID NO:29	5221 bp
NOV3g,	ATAAAAGGGGGCTGAGGAAATACCGGACACGGTCACCCGTTGCCAGCTCTAGCCTTTAAATTCCCGG
CG105521-01
DNA Sequence	CTCGGGGACCTCCACGCACCGCGGCTAGCGCCGACAACCAGCTAGCGTGCAAGGCGCCGCGGCTCAG
	CGCGTACCGGCCGOCTTCGAAACCGCAGTCCTCCGGCGACCCCGAACTCCGCTCCGGAGCCTCAGCC
	CCCTGGAAAGTGATCCCGGCATCCGAGAGCCAAGATGCCGGCCCACTTGCTGCAGGACGATATCTCT
	AGCTCCTATACCACCACCACCACCATTACAGCGCCTCCCTCCAGGGTCCTCCAGAATGGAGGAGATA
	AGTTGGAGACGATGCCCCTCTACTTGGAAGACGACATTCGCCCTGATATAAAAGATGATATATATGA
	CCCCACCTACAAGGATAAGGAAGGCCCAAGCCCCAACGTTGAATATGTCTGGAGAAACATCATCCTT
	ATGTCTCTGCTACACTTGGGAGCCCTGTATGGGATCACTTTGATTCCTACCTGCAAGTTCTACACCT
	GGCTTTGGGGGGTATTCTACTATTTTGTCAGTGCCCTGGGCATAACAGCAGGAGCTCATCGTCTGTG
	GAGCCACCGCTCTTACAAAGCTCGGCTGCCCCTACGGCTCTTTCTGATCATTGCCAACACAATGGCA
	TTCCAGAATGATGTCTATGAATGGGCTCGTGACCACCGTGCCCACCACAAGTTTTCACAAACACATG
	CTGATCCTCATAATTCCCGACGTGGCTTTTTCTTCTCTCACGTGGGTTGGCTGCTTGTGCGCAAACA
	CCCAGCTGTCAAAGAGAAGGGGAGTACGCTAGACTTGTCTGACCTAGAAGCTGAGAAACTGGTCATG
	TTCCAGAGGAGGTACTACAAACCTGGCTTGCTGCTGATGTGCTTCATCCTGCCCACGCTTGTGCCCT
	GGTATTTCTGGGOTGAAACTTTTCAAAACAGTGTGTTCGTTGCCACTTTCTTGCGATATGCTGTGGT
	GCTTAATGCCACCTGGCTGGTCAACAGTGCTGCCCACCTCTTCGGATATCGTCCTTATGACAAGAAc
	ATTAGCCCCCGGGAGAATATCCTGGTTTCACTTGGAGCTGTGGGTGAGGGCTTCCACAACTACCACC
	ACTCCTTTCCCTATGACTACTCTGCCAGTGAGTACCGCTGGCACATCAACTTCACCACATTCTTCAT
	TGATTGCATGGCCGCCCTCGGTCTGGCCTATGACCGGAAGAAAGTCTCCAAGGCCGCCATCTTGGCC
	AGGATTAAAAGAACCGGAGATGGAAACTACAAGAGTGGCTGAGTTTGGGGTCCCTCAGGTTTCCTTT
	TTCAAAAACCAGCCAGGCAGAGGTTTTAATGTCTGTTTATTAACTACTGAATAATGCTACCAGGATG
	CTAAAGATGATGATGTTAACCCATTCCAGTACAGTATTCTTTTAAAATTCAAAAGTATTGAAAGCCA
	ACAACTCTGCCTTTATGATGCTAAGCTGATATTATTTCTTCTCTTATCCTCTCTCTCTTCTAGGCCC
	ATTGTCCTCCTTTTCACTTTATTGCTATCGCCCTCCTTTCCCTTATTGCCTCCCAGGCAAGCAGCTG
	GTCAGTCTTTGCTCAGTGTCCAGCTTCCAAAGCCTAGACAACCTTTCTGTAGCCTAAAACGAATGGT
	CTTTGCTCCAGATAACTC~CTTTCCTTGAGCTGTTGTGAGCTTTGAAGTAGGTGGCTTGAGCTAGAG
	ATAAAACAGAATCTTCTGGGTAGTCCCCTGTTGATTATCTTCAGCCCAGGCTTTTGCTAGATGGAAT
	GGAAAAGCAACTTCATTTGACACAAAGCTTCTAAAGCAGGTAAATTGTCGGGGGAGAGAGTTAGCAT
	GTATGAATGTAAGGATGAGGGAAGCGAAGCAAGACGAACCTCTCGCCATGATCAGACATACAGCTGC
	CTACCTAATGAGGACTTCAAGCCCCACCACATAGCATGCTTCCTTTCTCTCCTGGCTCGGGGTAAAA
	AGTGGCTGCGGTGTTTGGCAATGCTAATTCAATGCCGCAACATATAGTTGAGGCCGAGGATAAAGAA
	AAGACATTTTAAGTTTGTAGTAAAAGTGGTCTCTGCTGGGGAAGGGTTTTCTTTTCTTTTTTTCTTT
	AATAACAAGGAGATTTCTTAGTTCATATATCAAGAAGTCTTGAAGTTGGGTGTTTCCAGAATTGGTA
	AAAACAGCAGCTCATGGAATTTTGAGTATTCCATGAGCTGCTCATTACAGTTCTTTCCTCTTTCTGC
	TCTGCCATCTTCAGGATATTGGTTCTTCCCCTCATAGTAATAAGATGGCTGTGGCATTTCCAAACAT
	ACAAAAAAAGGGAAGGATTTAAGGAGGTGAAGTCGGGTCAAAAATAAAATATATATACATATATACA
	TTGCTTAGAACGTTAAACTATTAGAGTATTTCCCTTCCAAAGAGGGATGTTTGGAAAAAACTCTGAA
	GGAGAGGAGGAATTAGTTGGGATGCCAATTTCCTCTCCACTGCTGGACATGAGATGGAGAGGCTGAG
	GGACAGGATCTATAGGCAGCTTCTAAGAGCGAACTTCACATAGGAAGGGATCTGAGAACACGTTGCC
	AGGGGCTTGAGAAGGTTACTGAGTGAGTTATTGGGAGTCTTAATAAAATAAACTAGATATTAGGTCC
	ATTCATTAATTAGTTCCAGTTTCTCCTTGAAATGAGTAAAAACTAGAAGGCTTCTCTCCACAGTGTT
	GTGCCCCTTCACTCATTTTTTTTTGAGGAGAAGGGGGTCTCTGTTAACATCTAGCCTAAAGTATACA
	ACTGCCTGGGGGGCAGGGTTAGGAATCTCTTCACTACCCTGATTCTTGATTCCTGGCTCTACCCTGT
	CTGTCCCTTTTCTTTGACCAGATCTTTCTCTTCCCTGAACGTTTTCTTCTTTCCCTGGACAGGCAGC
	CTCCTTTGTGTGTATTCAGAGGCAGTGATGACTTGCTGTCCAGGCAGCTCCCTCCTGCACACAGAAT
	ACTCAGCGTCACTGAACCACTGCTTCTCTTTTGAAAGTAGAGCTAGCTGCCACTTTCACGTGGCCTC
	CGCAGTGTCTCCACCTACACCCCTGTGCTCCCCTGCCACACTGATGGCTCAAGACAAGGCTGGCAAA
	CCCTCCCAGAAACATCTCTGGCCCAGAAAGCCTCTCTCTCCCTCCCTCTCTCATGAGGCACAGCCAA
	GCCAAGCGCTCATGTTGAGCCAGTGCGCCAGCCACAGAGCAAAAGAGGGTTTATTTTCAGTCCCCTC
	TCTCTGGGTCAGAACCAGAGGGCATGCTGAATGCCCCCTGCTTACTTGGTGAGGGTGCCCCGCCTGA
	GTCAGTGCTCTCAGCTGGCAGTGCAATGCTTGTAGAAGTAGGAGGAAACAGTTCTCACTGGGAAGAA
	ACAAGGGCAAGAACCCAAGTGCCTCACCTCGAAAGGAGGCCCTGTTCCCTGGAGTCAGGGTGAACTG
	CAAAGCTTTGCCTGAGACCTGGGATTTGAGATACCACAAACCCTGCTGAACACAGTGTCTGTTCAGC
	AAACTAACCAGCATTCCCTACAGCCTAGGGCAGACAATAGTATAGAAGTCTGGAAAAAAACAAAAAC
	AGAATTTGAGAACCTTGGACCACTCCTGTCCCTGTAGCTCAGTCATCAAAGCAGAAGTCTGGCTTTG
	CTCTATTAAGATTGGAAATGTACACTACCAAACACTCAGTCCACTGTTGAGCCCCAGTGCTGGAAGG
	CAGGAAGGCCTTTCTTCTGTGTTAATTGCGTAGAGGCTACAGGGGTTAGCCTGGACTAAAGGCATCC
	TTGTCTTTTGAGCTATTCACCTCAGTAGAAAAGGATCTAAGGGAAGATCACTGTAGTTTAGTTCTGT
	TGACCTGTGCACCTACCCCTTGGAAATGTCTGCTGGTATTTCTAATTCCACAGGTCATCAGATGCCT
	GCTTGATAATATATAAACAATAAAAACAACTTTCACTTCTTCCTATTGTAATCGTGTGCCATGGATC
	TGATCTGTACCATGACCCTACATAAGGCTGGATGGCACCTCAGGCTGACGGCCCCAATGTATGTGTG
	GCTGTGGGTGTGGGTGGGAGTGTGTCTGCTGAGTAAGGAACACGATTTTCAAGATTCTAAAGCTCAA
	TTCAAGTGACACATTAATGATAAACTCAGATCTGATCAAGAGTCCGGATTTCTAACAGTCCCTGCTT
	TGGGGGGTGTGCTGACAACTTAGCTCAGGTGCCTTACATCTTTTCTAATCACAGTGTTGCATATGAG
	CCTGCCCTCACTCCCTCTGCAGAATCCCTTTGCACCTGAGACCCTACTGAAGTGGCTGGTAGAAAAA
	GGGGCCTGAGTGGAGGATTATCAGTATCACGATTTGCAGGATTCCCTTCTGGGCTTCATTCTGGAAA
	CTTTTGTTAGGGCTGCTTTTCTTAAGTGCCCACATTTGATGGAGGGTGGAAATAATTTGAATGTATT
	TGATTTATAAGTTTTTTTTTTTTTTTGGGTTAAAAGATGGTTGTACCATTTAAAATGGAAAATTTTC
	TCCTTGGTTTGCTAGTATCTTGGGTGTATTCTCTGTAAGTGTAGCTCAAATAGGTCATCATGAAAGG
	TTAAAAAAGCGAGGTGGCCATGTTATGCTGGTGGTTAAGGCCAGGGCCTCTCCAACCACTGTGCCAC
	TGACTTGCTGTGTGACCCTGGGCAAGTCACTTAACTATAAGGTGCCTCAGTTTTCCTTCTGTTAAAA
	TGGGGATAATAATACTGACCTACCTCAAAGGGCAGTTTTGAGGCATGACTAATGCTTTTTAGAAAGC
	ORF Start: ATG at 236		ORF Stop: TGA at 1313
	SEQ ID NO: 30	359 aa	MW at 41504.1kD
NOV3g,	MPAHLLQDDISSSYTTTTTITAPPSRVLQNGGDKLETMPLYLEDDIRPDIKDDIYDFTYKDKEGPSP
CG105521-01
Protein	KVEYVWRNIILMSLLHLGALYGITLIPTCKFYTWLWGVFYYFVSALGITAGAHRLWSHRSYKARLPL
Sequence
	RLFLIIANTMAFQNDVYEWARDHRAHHKFSETHADPHNSRRGFFFSHVGWLLVRKHPAVKEKGSTLD
	LSDLEAEKLVMFQRRYYKPGLLLMCFILPTLVPWYFWGETFQNSVFVATFLRYAVVLNATWLVNSAA
	HLFGYRPYDKNISPREUILVSLGAVGEGFHNYHHSFPYDYSASEYRWHINFTTFFIDCMAALGLAYD
	RKKVSKAAILARIKRTGDGNYKSG
	SEQ ID NO: 31	1420bp
NOV3h,	ATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCACAGCTCTCTGGCTAACTAGAGAACCCA
212779051
DNA Sequence	CTGCTTACTGGCTTATCGAAATTAATACGACTCACTATAGGGAGACCCAAGCTGGCTAGCGTTTAAA
	CTTAAGCTTGGTACCGAGCTCGGATCCACCATGCCGGCCCACTTGCTGCAGGACGATATCTCTAGCT
	CCTATACCACCACCACCACCATTACAGCGCCTCCCTCCAGGGTCCTGCAGAATGGAGGAGATAAGTT
	GGAGACGAPGCCCCTCTACTTGGAAGACGACATTCGCCCTGATATAAAAGATGATATATATGACCCC
	ACCTACAAGGATAAGGAAGGCCCAAGCCCCAAGGTTGAATATGTCTGGAGAAACATCATCCTTATGT
	CTCTGCTACACTTGGGAGCCCTGTATGGGATCACTTTGATTCCTACCTGCAAGTTCTACACCTGGCT
	TTGGGGGGTATTCTACTATTTTGTCAGTGCCCTGGGCATAACAGCAGGAGCTCATCGTCTGTGGAGC
	CACCGCTCTTACAAAGCTCGGCTGCCCCTACGGCTCTTTCTGATCATTGCCAACACAATGGCATTCC
	AGAATGATGTCTATGAATGGGCTCGTGACCACCGGGCCCACCACAAGTTTTCAGAAACACATGCTGA
	TCCTCATAATTCCCGACGTGGCTTTTTCTTCTCTCACGTGGGTTGGCTGCTTGTGCGCAAACACCCA
	GCTGTCAAAGAGAAGGGGAGTACGCTAGACTTGTCTGACCTAGAAGCTGAGAAACTGGTGATGTTCC
	AGAGGAGGTACTACAAACCTGGCTTGCTGCTGATGTGCTTCATCCTGCCCACGCTTGTGCCCTGGTA
	TTTCTGGGGTGAAACTTTTCAAAACAGTGTGTTCGTTGCCACTTTCTTGCGATATGCTGTGGTGCTT
	AATGCCACCTGGCTGGTGAACAGTGCTGCCCACCTCTTCGGATATCGTCCTTATGACAAGAACATTA
	GCCCCCGGGAGAATATCCTGGTTTCACTTGGAGCTCTGGGTGAGGGCTTCCACAACTACCACCACTC
	CTTTCCCTATGACTACTCTGCCAGTGAGTACCGCTGGCACATCAACTTCACCACATTCTTCATTGAT
	TGCATGGCCGCCCTCGGTCTGGCCTATGACCGGAAGAAAGTCTCCAAGGCCGCCATCTTGGCCAGGA
	TTAAAAGAACCGGAGATGGAAACTACAAGAGTGGCTGAGCGGCCGCTCGAGTCTAGAGGGCCCGTTT
	AAACCCGCTGATCAGCCTCCACTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGT
	GCCTTCCTTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCG
	CATTGTCTGAGTT
	ORF Start: at 108		ORF Stop: TGA at 1242
	SEQ ID NO:32	378 aa	MW at 43506.4kD
NOV3h,	GDPSWLAFKLKLGTELGSTMPAHLLQDDISSSYTTTTTITAPPSRVLQNGGDKLETMPLYLEDDIRP
212779051
Protein	DIKDDIYDPTYKDKEGPSPKVEYVWRNTILMSLLHLGALYGITLIPTCKFYTWLWGVFYYFVSALGI
Sequence
	TAGAHRLWSHRSYKARLPLRLFLIIANTMAFQNDVYEWARDHRAHHKFSETHADPHNSRRGFFFSHV
	GWLLVRKHPAVKEKGSTLDLSDLEAEKLVMFQRRYYKPGLLLMCFILPTLVPWYFWGETFQNSVFVA
	TFLRYAVVLNATWLVNSAAHLFGYRPYDKNISPRENILVSLGAVGEGFHIYHHSFPYDYSASEYRWH
	INFTTFFIDCMAALGLAYDRKKVSKAAILARIKRTGDGNYXSG
	SEQ ID NO:33	5221 bp
NOV3i,	ATAAAAGGGGGCTGAGGAAATACCGGACACGGTCACCCGTTGCCAGCTCTAGCCTTTAAATTCCCGGC
CG105521-01
DNA Sequence	TCGGGGACCTCCACGCACCGCGGCTAGCGCCGACAACCAGCTAGCGTGCAAGGCGCCGCGGCTCAGCC
	CGTACCGGCGGGCTTCGAAACCGCAGTCCTCCGGCGACCCCGAACTCCGCTCCGGAGCCTCAGCCCCC
	TGGAAAGTGATCCCGGCATCCGAGAGCCAAGATGCCGGCCCACTTGCTGCAGGACGATATCTCTAGCT
	CCTATACCACCACCACCACCATTACAGCGCCTCCCTCCAGGGTCCTGCAGAATGGAGGAGATAAGTTG
	GAGACGATGCCCCTCTACTTGGAAGACGACATTCGCCCTGATATAAAAGATGATATATATGACCCCAC
	CTACAAGGATAAGGAAGGCCCAAGCCCCAAGGTTGAATATGTCTGGAGAAACATCATCCTTATGTCTC
	TGCTACACTTGGGAGCCCTGTATGGGATCACTTTGATTCCTACCTGCAAGTTCTACACCTGGCTTTGG
	CGGGTATTCTACTATTTTGTCAGTGCCCTGGGCATAACAGCAGGAGCTCATCGTCTGTc~GAGCCACCG
	CTCTTACAAAGCTCGGCTGCCCCTACGGCTCTTTCTGATCATTGCCAACACAATGGCATTCCAGAATG
	ATGTCTATGAATGGGCTCGTGACCACCGTGCCCACCACAAGTTTTCAGAAACACATGCTGATCCTCAT
	AATTCCCGACGTGGCTTTTTCTTCTCTCACGTGGGTTGCCTGCTTGTGCGCAAACACCCAGCTGTCAA
	AGAGAAGGGGAGTACGCTAGACTTGTCTGACCTAGAAGCTGAGAAACTGGTGATGTTCCAGAGGAGGT
	ACTACAAACCTGGCTTGCTGCTGATGTGCTTCATCCTGCCCACGCTTGTGCCCTGGTATTTCTGGGGT
	GAAACTTTTCAAAACAGTGTGTTCGTTGCCACTTTCTTGCGATATGCTGTGGTGCTTAATGCCACCTG
	GCTGGTGAACAGTGCTGCCCACCTCTTCGGATATCGTCCTTATGACAAGAACATTAGCCCCCGGGAGA
	ATATCCTGGTTTCACTTGGAGCTGTGGGTGAGGGCTTCCACAACTACCACCACTCCTTTCCCTATGAC
	TACTCTGCCAGTGAGTACCGCTGGCACATCAACTTCACCACATTCTTCATTGATTGCATGGCCGCCCT
	CGGTCTGGCCTATGACCGGAAGAAAGTCTCCAAGGCCGCCGTCTTGGCCAGGATTAAAAGAACCGGAG
	ATGGAAACTACAAGAGTGGCTGAGTTTGGGGTCCCTCAGGTTTCCTTTTTCAAAAACCAGCCAGGCAG
	AGGTTTTAATGTCTGTTTATTAACTACTGAATAATGCTACCAGGATGCTAAAGATGATGATGTTAACC
	CATTCCAGTACAGTATTCTTTTAAAATTCAAAAGTATTGAAAGCCAACAACTCTGCCTTTATGATGCT
	AAGCTGATATTATTTCTTCTCTTATCCTCTCTCTCTTCTAGQCCCATTGTCCTCCTTTTCACTTTATT
	CCTATCGCCCTCCTTTCCCTTATTGCCTCCCAGGCAAGCAGCTGGTCAGTCTTTGCTCAGTGTCCAGC
	TTCCAAAGCCTAGACAACCTTTCTGTAGCCTAAAACGAATGGTCTTTGCTCCAGATAACTCTCTTTCC
	TTGAGCTGTTGTGAGCTTTGAAGTAGGTGGCTTGAGCTAGAGATAAAACAGAATCTTCTGGGTAGTCC
	CCTGTTGATTATCTTCAGCCCACGCTTTTGCTAGATGGAATGGAAAAGCAACTTCATTTCACACAAAC
	CTTCTAAAGCAGGTAAATTGTCGGGGGAGAGAGTTAGCATGTATGAATGTAAGGATGAGGGAAGCGAA
	CCAAGAGGAACCTCTCGCCATGATCAGACATACAGCTGCCTACCTAATGAGGACTTCAAGCCCCACCA
	CATAGCATGCTTCCTTTCTCTCCTGGCTCGGGGTAAAAAGTGGCTGCGGTGTTTGGCAATGCTAATTC
	AATGCCGCAACATATAGTTGAGGCCGAGGATAAAGAAAAGACATTTTAAGTTTGTAGTAAAAGTCGTC
	TCTGCTGGGGAAGGGTTTTCTTTTCTTTTTTTCTTTAATAACAAGGAGATTTCTTAGTTCATATATCA
	AGAAGTCTTGAAGTTGGGTGTTTCCAGAATTGGTAAAAACAGCAGCTCATGGAATTTTGAGTATTCCA
	TGAGCTGCTCATTACAGTTCTTTCCTCTTTCTGCTCTGCCATCTTCAGGATATTGGTTCTTCCCCTCA
	TAGTAATAAGATGGCTGTGGCATTTCCAAACATCCAAAAAAAGGGAAGGATTTAAGGAGGTGAAGTCG
	GGTCAAAAATAAAATATATATACATATATACATTGCTTAGAACGTTAAACTATTAGAGTATTTCCCTT
	CCAAAGAGGGATGTTTGCAAAAAACTCTGAAGGAGAGGAGGAATTAGTTGGGATGCCAATTTCCTCTC
	CACTGCTGGACATGAGATGGAGAGGCTGAGGGACAGGATCTATAGGCAGCTTCTAAGAGCGAACTTCA
	CATACGAAAGGATCTGAGAACACGTTCCCAGGGGCTTGAGAAGGTTACTGACTGAGTTATTGGGAGTC
	TTAATAAAATAAACTAGATATTAGGTCCATTCATTAATTAGTTCCAGTTTCTCCTTGAAATGAGTAAA
	AACTAGAAGGCTTCTCTCCACAGTGTTGTGCCCCTTCACTCATTTTTTTTTGAGGAGAAGGGGGTCTC
	TGTTAACATCTAGCCTAAAGTATACAACTGCCTGGGGGGCAGGGTTAGGAATCTCTTCACTACCCTGA
	TTCTTGATTCCTGGCTCTACCCTGTCTGTCCCTTTTCTTTGACCATATCTTTCTCTTCCCTGAACGTT
	TTCTTCTTTCCCTGGACAGGCAGCCTCCTTTGTGTGTATTCAGAGGCAGTGATGACTTGCTGTCCAGG
	CAGCTCCCTCCTGCACACAGAATGCTCAGGGTCACTGAACCACTGCTTCTCTTTTGAAAGTAGAGCTA
	GCTGCCACTTTCACGTGGCCTCCGCAGTGTCTCCACCTACACCCCTGTGCTCCCCTGCCACACTGATG
	GCTCAAGACAACGCTGGCAAACCCTCCCAGAAACATCTCTGGCCCAGAAAGCCTCTCTCTCCCTCCCT
	CTCTCATGAGGCACAGCCAAGCCAAGCGCTCATGTTGAGCCAGTGGGCCAGCCACAGAGCAAAAGAGG
	GTTTATTTTCAGTCCCCTCTCTCTGGGTCAGAACCAGAGGGCATGCTGAATGCCCCCTGCTTACTTGG
	TGAGGGTGCCCCGCCTGAGTCAGTGCTCTCAGCTGGCAGTGCAATGCTTCTAGAAGTAGGAGGAAACA
	GTTCTCACTGGGAAGAAGCAACGGCAAGAACCCAAGTGCCTCACCTCGAAAGGAGGCCCTGTTCCCTG
	GAGTCAGGGTGAACTGCAAAGCTTTGGCTGAGACCTGGGATTTGAGATACCACAAACCCTGCTGAACA
	CAGTGTCTGTTCAGCAAACThACCAGCATTCCCTACAGCCTAGGGCAGACAATAGTATAAAAGTCTGG
	AAAAAAACAAAAACAGAATTTGAGAACCTTGGACCACTCCTGTCCCTGTAGCTCAGTCATCAAAGCAG
	AAGTCTGGCTTTGCTCTATTAAGATTGGAAATGTACACTACCAAACACTCAGTCCACTGTTGAGCCCC
	AGTGCTGGAAGGGAGGAAGGCCTTTCTTCTGTGTTAATTGCGTAGAGGCTACAGGGGTTAGCCTGGAC
	TAAAGGCATCCTTGTCTTTTGAGCTATTCACCTCAGTAGAAAAGGATCTAAGGGAAGATCACTGTAGT
	TTAGTTCTOTTGACCTGTGCACCTACCCCTTGGAAATCTCTCCTGGTATTTCTAATTCCACAGGTCAT
	CAGATGCCTGCTTGATAATATATAAACAATAAAAACAACTTTCACTTCTTCCTATTGTAATCCTGTGC
	CATGGATCTGATCTGTACCATGACCCTACATAAGGCTGGATGGCACCTCAGGCTGAGGGCCCCAATGT
	ATGTGTGGCTGTGGGTGTGGGTGGGAGTGTGTCTGCTGAGTAAGGAACACGATTTTCAAGATTCTAAA
	GCTCAATTCAAGTGACACATTAATGATAAACTCAGATCTGATCAAGAGTCCGGATTTCTAACAGTCCC
	TGCTTTGGGGGGTGTGCTGACAACTTAGCTCAGGTGCCTTACATCTTTTCTAATCACAGTGTTGCATA
	TGAGCCTGCCCTCACTCCCTCTGCAGAATCCCTTTGCACCTGAGACCCTACTGAAGTGGCTGGTAGAA
	AAAGGGGCCTGAGTGGAGGATTATCAGTATCACGATTTCCAGGATTCCCTTCTGGGCTTCATTCTGGA
	AACTTTTGTTAGGGCTGCTTTTCTTAAGTGCCCACATTTGATGGAGGGTGGAAATAATTTGAATGTAT
	TTGATTTATAAGTTTTTTTTTTTTTTTGCGTTAAAAGATGGTTGTAGCATTTAAAATGGAAAATTTTC
	TCCTTGGTTTGCTAGTATCTTGGGTGTATTCTCTGTAAGTGTAGCTCAAATAGGTCATCATGAAAGGT
	TAAAAAAGCGAGGTGGCCATGTTATGCTGGTGGTTAAGGCCAGGGCCTCTCCAACCACTGTGCCACTG
	ACTTGCTGTGTGACCCTGGGCAAGTCACTTAACTATAAGGTGCCTCAGTTTTCCTTCTGTTAAAATGG
	GGATAATAATACTGACCTACCTCAAAGGGCAGTTTTGAGGCATGACTAATGCTTTTTAGAAAGCATTT
	TGGGATCCTTCAGCACAGGAATTCTCAAGACCTGAGTATTTTTTATAATAGGAATGTCCACCATGAAC
	TTGATACGTCCGTGTGTCCCAGATGCTGTCATTAGTCTATATGGTTCTCCAAGAAACTGAATGAATCC
	ATTGGAGAAGCCGTGGATAACTAGCCAGACAAAATTTGAGAATACATAAACAACGCATTGCCACGGAA
	ACATACAGACGATGCCTTTTCTGTGATTGGGTGGGATTTTTTCCCTTTTTATGTGGGATATAGTAGTT
	ACTTGTGACAAAAATAATTTTGGAATAATTTCTATTAATATCAACTCTGAAGCTAATTGTACTAATCT
	GAGATTGTGTTTGTTCATAATAAAGTGAAGTGAATCTAAAAAAAAAAAAAAAA
	ORF Start: ATG at 236		ORF Stop: TGA at 1313
	SEQ ID NO: 34	359 aa	MW at 41504.1kD
NOV3i,	MPAHLLQDDISSSYTTTTTITAPPSRVLQNGGDKLETMPLYLEDDIRPDIKDDIYDPTYKDKEGPSPK
CG105521-01
Protein	VEYVWRNIILMSLLHLGALYGITLIPTCKFYTWLWGVFYYFVSALGITAGAHRLWSHRSYKARLPLRL
Sequence
	FLIIANTMAFQNDVYEWARDHRAHHKFSETHADPHNSRRGFFFSHVGWLLVRKHPAVKEKGSTLDLSD
	LEAEKLVMFQRRYYKPGLLLMCFILPTLVPWYFWGETFQNSVFVATFLRYAVVLNATWLVNSAAHLFG
	YRPYDKNISPRENILVSLGAVGEGFHNYHHSFPYDYSASEYRWHINFTTFFIDCMAALGLAYDRXKVS
	KAAILARIRRTGDGNYKSG
	SEQ ID NO:35	1089 bp
NOV3j,	ACCATGCCGGCCCACTTGCTGCAGGACGATATCTCTAGCTCCTATACCACCACCACCACCATTACAGC
308782133
DNA Sequence	GCCTCCCTCCAGGGTCCTGCAGAATGGAGGAGATAAGTTGGAGACGATGCCCCTCTACTTGGAAGACG
	ACATTCGCCCTGATATAAAAGATGATATATATGACCCCACCTACAAGGATAAGGAAGGCCCAAGCCCC
	AAGGTTGAATATGTCTGGAGAAACATCATCCTTATGTCTCTGCTACACTTGGGAGCCCTGTATGGGAT
	CACTTTGATTCCTACCTGCAAGTTCTACACCTGGCTTTGGGGGGTATTCTACTATTTTGTCAGTGCCC
	TGGGCATAACAGCAGGAGCTCATCGTCTGTGGAGCCACCGCTCTPACAAAGCTCGGCTGCCCCTACGG
	CTCTTTCTGATCATTGCCAACACAATGGCATTCCAGAATCATGTCTATGAATGGGCTCGTGACCACCG
	TGCCCACCACAAGTTTTCAGAAACACATGCTGATCCTCATAATTCCCGACGTGGCTTTTTCTTCTCTC
	ACGTGGGTTCGCTGCTTGTGCGCAAACACCCAGCTGTCAAAGAGAAGCGGAGTACGCTAGACTTGTCT
	GACCTAGAAGCTGAGAAACTGGTGATGTTCCAGAGGAGGTACTACAAACCTGGCTTGCTGATGATGTG
	CTTCATCCTCCCCACGCTTGTGCCCTCGTATTTCTGGGGTGAAACTTTTCAAAACAGTGTGTTCGTTG
	CCACTTTCTTGCGATATGCTGTGGTGCTTAATGCCACCTGGCTGGTGAACAGTGCTGCCCACCTCTTC
	GCATATCGTCCTTATGACAAGAACATTAGCCCCCGGGAGAATATCCTCGTTTCACTTCGAGCTGTGGG
	TGAGGGCTTCCACAACTACCACCACTCCTTTCCCTATGACTACTCTGCCAGTGAGTACCGCTGGCACA
	TCAACTTCACCACATTCTTCATTGATTGCATGGCCGCCCTCGGTCTGGCCTATGACCCGAAGAAAGTC
	TCCAAGGCCGCCATCTTGGCCAGGATTAAAAGAACCGGAGATGGAAACTACAAGAGTGGCTGAGCAGG
	T
	ORF Start: at 1		ORF Stop: TGA at 1081
	SEQ ID NO:36	360 aa	MW at 41623.3kD
NOV3j,	TMPAHLLQDDISSSYTTTTTITAPPSRVLQNGGDKLETMPLYLEDDIRPDIKDDIYDPTYKDKEGPSP
308782133
Protein	KVEYVWRNIILMSLLHLGALYGITLIPTCKFYTWLWGVFYYFVSALGITAGAHRLWSHRSYKARLPLR
Sequence
	LFLIIANTMAFQNDVYEWARDHRAHHKFSETHADPHNSRRGFFFSHVGWLLVRKHPAVKEKGSTLDLS
	DLEAEKLVMFQRRYYKPGLLMMCFILPTLVPWYFWGETFQNSVFVATFLRYAVVLNATWLVNSAAHLF
	GYRPYDKNISPRENILVSLGAVGEGFHNYHHSFPYDYSASEYRWHINFTTFFIDCMAALGLAYDRKKV
	SKAAILARIKRTGDGNYKSG
	SEQ ID NO:37	1104 bp
NOV3k,	ACCATGGGACATCATCACCACCATCACCCGGCCCACTTGCTGCAGGACGATATCTCTAGCTCCTATA
CG105521-03
DNA Sequence	CCACCACCACCACCATTACAGCGCCTCCCTCCAGGGTCCTGCAGAATGGAGGAGATAAGTTGGAGAC
	GATGCCCCTCTACTTGGAAGACGACATTCGCCCTGATATAAAAGATGATATATATGACCCCACCTAC
	AAGGATAAGGAAGGCCCAAGCCCCAAGGTTGAATATGTCTGGAGAAACATCATCCTTATGTCTCTGC
	TACACTTGGGAGCCCTGTATGGGATCACTTTGATTCCTACCTGCAAGTTCTACACCTGGCTTTGGGG
	CGTATTCTACTATTTTGTCAGTCCCCTGGGCATAACAGCAGGAGCTCATCGTCTGTGGAGCCACCGC
	TCTTACAAAGCTCGGCTGCCCCTACGGCTCTTTCTGATCATTGCCAACACAATGGCATTCCAGAATG
	ATGTCTATGAATGGGCTCGTGACCACCGTGCCCACCACAAGTTTTCAGAAACACATGCTGATCCTCA
	TAATTCCCGACGTGGCTTTTTCTTCTCTCACGTGGGTTGGCTGCTTGTGCGCAAACACCCAGCTGTC
	AAAGAGAAGGGGAGTACGCTAGACTTGTCTGACCTAGAAGCTGAGAAACTGGTGATGTTCCAGAGGA
	GGTACTACAAACCTGGCTTGCTGATGATGTGCTTCATCCTCCCCACGCTTGTGCCCTGGTATTTCTG
	GGGTGAAACTTTTCAAAACAGTGTGTTCGTTGCCACTTTCTTGCGATATGCTGTGGTGCTTAATGCC
	ACCTGGCTGGTGAACAGTGCTCCCCACCTCTTCGGATATCGTCCTTATGACAAGAACATTAGCCCCC
	GGGAGAATATCCTGGTTTCACTTGGAGCTGTGGGTGAGGGCTTCcACAAcTACCACCACTccTTTcc
	CTATGACTACTCTCCCAGTGAGTACCGCTCGCACATCAACTTCACCACATTCTTCATTGATGCATG
	GCCGCCCTCGGTCTGGCCTATGACCGGAAGAAAGTCTCCAAGGCCGCCATCTTGGCCAGGATTAAAA
	GAACCGOACATGGAAACTACAAGACTGGCTGA
	ORF Start: at 1		ORF Stop: TGA at 1102
	SEQ ID NO: 38	367 aa	MW at 42503.2kD
NOV3k,	TMGHHHHHHPAHLLQDDISSSYTTTTTITAPPSRVLQNGGDKLETMFLYLEDDIRPDIKDDIYDPTY
CG105521-03
Protein	KDKEGPSPKVEYVWRNIILMSLLHLGALYGITLIPTCKFYTWLWGVFYYFVSALGITAGABRLWSHR
Sequence
	SYKARLPLRLFLIIANTMAFQNDVYEWARDHRAHHKFSETHADPHNSRRGFFFSHVGWLLVRKHPAV
	KEKGSTLDLSDLEAEKLVMFQRRYYKPGLLMMCFILPTLVPWYFWGETFQNSVFVATFLRYAVVLNA
	TWLVNSAAHLFGYRPYDKNISPRENILVSLGAVGEGFHNYHHSFPYDYSASEYRWHINFTTFFIDCM
	AALGLAYDRKKVSKAAILARIKRTGDGNYKSG
	SEQ ID NO:39	1138 bp
NOV31,	GCCGAATTCTCAGCCCCTGGAAAGTGATCCCGGCATCCGAGAGCCAAGATGCCGGCCCACTTGCTGCA
CG105521-04
DNA Sequence	GGACGATATCTCTAGCTCCTATACCACCACCACCACCATTACAGCGCCTCCCTCCAGGCTCCTGCAGA
	ATGGAGGAGATAAGTTGGAGACGATGCCCCTCTACTTCGAAGACGACATTCGCCCTGATATAAAAGAT
	GATATATATGACCCCACCTACAAGGATAAGGAAGGCCCAAGCCCCAAGGTTGAATATGTCTGGAGAAA
	CATCATCCTTATGTCTCTGCTACACTTGGGAGCCCTGTATGCGATCACTTTGATTCCTACCTGCAAGT
	TCTACACCTGGCTTTGGGGGGTATTCTACTATTTTGTCAGTGCCCTGGGCATAACAGCAGGAGCTCAT
	CGTCTGTGGAGCCACCGCTCTTACAAAGCTCGGCTGCCCCTACGGCTCTTTCTGATCATTGCCAACAC
	AATCGCATTCCAGAATGATGTCTATGAATGGGCTCGTGACCACCGTGCCCACCACAAGTTTTCAGAAC
	CACATGCTGATCCTCATAATTCCCGACGTGGCTTTTTCTTCTCTCACGTGGGTTGGCTGCTTGTCCGC
	AAACACCCAGCTGTCAAAGAGAAGGGGAGTACGCTAGACTTGTCTGACCTAGAAGCTGAGAAACTGGT
	GATGTTCCAGAGGAGGTACTACAAACCTGGCTTGCTGATGATGTGCTTCATCCTGCCCACGCTTGTGC
	CCTGGTATTTCTGGGGTGAAACTTTTCAAAACAGTGTGTTCGTTGCCACTTTCTTGCGATATGCTGTG
	GTGCTTAATGCCACCTGGCTGGTGAACAGTGCTGCCCACCTCTTCGGATATCGTCCTTATGACAAGAA
	CATTAGCCCCCGGGAGAATATCCTGGTTTCACTTGGAGCTGTGGGTGAGGGCTTCCACAACTACCACC
	ACTCCTTTCCCTATGACTACTCTGCCAGTGAGTACCGCTGCCACATCAACTTCACCACATTCTTCATT
	GATTGCATGGCCGCCCTCGGTCTGGCCTATGACCGGAAGAAAGTCTCCAAGGCCGCCATCTTGGCCAG
	GATTAAAAGAACCGGAGATGGAAACTACAAGAGTGGCTGAGGATCCGGTG
	ORF Start: ATG at 49		ORF Stop: TGA at 1126
	SEQ ID NO: 40	359 aa	MW at 41522.2kD
NOV31,	MPAHLLQDDISSSYTTTTTITAPPSRVLQNGGDKLETMPLYLEDDIRPDIKDDTYDPTYKDKEGPSPK
CG105521-04
Protein	VEYVWRNIILMSLLHLGALYGITLIPTCKFYTWLWGVFYYFVSALGITAGAHRLWSHRSYKARLPLRL
Sequence
	FLIIANTMAFQNDVYEWARDHRAHHKFSETHADPHNSRRGFFFSHVGWLLVRKHPAVKEKGSTLDLSD
	LEAEKLVMFQRRYYKPGLLMMCFILPTLVPWYFWGETFQNSVFVATFLRYAVVLNATWLVNSAAHLFG
	YRPYDKNISPRENILVSLGAVGEGFHNYHHSFPYDYSASEYRWHINFTTFFIDCMAALGLAYDRKKVS
	KAAILARIKRTGDGNYKSG
	SEQ ID NO:41	1129 bp
NOV3m,	ACATCATCACCACCATCACCCGGCCCACTTGCTGCAGGACGATATCTCTAGCTCCTATACCACCACC
CG105521-05
DNA Sequence	ACCACCATTACAGCGCCTCCCTCCAGGGTCCTGCAGAATGGAGGAGATAAGTTGGAGACGATGCCCC
	TCTACTTGGAAGACGACATTCGCCCTGATATAAAAGATGATATATATGACCCCACCTACAAGGATAA
	GGAAGGCCCAAGCCCCAAGGTTGAATATGTCTGGAGAAACATCATCCTTATGTCTCTGCTACACTTG
	GGAGCCCTGTATGGGATCACTTTGATTCCTACCTGCAAGTTCTACACCTGGCTTTGGGGGGTATTCT
	ACTATTTTGTCAGTGCCCTGGGCATAACAGCAGGAGCTCATCGTCTGTGGAGCCACCGCTCTTACAA
	AGCTCGGCTGCCCCTACGGCTCTTTCTGATCATTGCCAACACAATGGCATTCCAGAATGATGTCTAT
	GAATGCGCTCGTGACCACCGTGCCCACCACAAGTTTTCAGAAACACATGCTGATCCTCATAATTCCC
	GACGTGGCTTTTTCTTCTCTCACGTGGGTTGGCTGCTTGTGCGCAAACACCCAGCTGTCAAAGAGAA
	GGGGAGTACGCTAGACTTGTCTGACCTAGAAGCTGAGAAACTGGTGATGTTCCAGAGOAGGTACTAC
	AAACCTGGCTTGCTGATGATGTGCTTCATCCTGCCCACGCTTGTGCCCTGGTATTTCTGGGGTGAAA
	CTTTTCAAAACAGTGTGTTCGTTGCCACTTTCTTGCGATATGCTGTGGTGCTTAATGCCACCTGGCT
	GGTGAACAGTGCTGCCCACCTCTTCGGATATCGTCCTTATGACAAGAACATTAGCCCCCGGGAGAAT
	ATCCTGGTTTCACTTGGAGCTGTGGGTGAGGGCTTCCACAACTACCACCACTCCTTTCCCTATGACT
	ACTCTGCCAGTGAGTACCGCTGGCACATCAACTTCACCACATTCTTCATTGATTGCATGGCCGCCCT
	CGGTCTGGCCTATGACCGGAAGAAAGTCTCCAAGGCCGCCATCTTGGCCAGGATTAAAAGAACCGGA
	GATGGAAACTACAAGAGTGGCTGAGCCGCCGCACTCGAGCACCACCACCACCACCAC
	ORF Start: at 2		ORF Stop: TGA at 1094
	SEQ ID NO: 42	364 aa	MW at 42213.9W
NOV3m,	HHHHHHPAHLLQDDISSSYTTTTTITAPPSRVLQNGGDKLETMPLYLEDDIRPDIKDDIYDPTYKDK
CG105521-05
Protein	EGPSPKVEYVWRNIILMSLLHLGALYGITLIPTCKFYTWLWGVFYYFVSALGITAGARRLWSHRSYK
Sequence
	ARLPLRLFLIIANTMAFQNDVYEWARDHRAHHKFSETHADPHNSRRGFFFSHVGWLLVRKHPAVKEK
	GSTLDLSDLEAEKLVMFQRRYYKPGLLMMCFILPTLVPWYFWGETFQNSVFVATFLRYAVVLNATWL
	VNSAAHLFGYRPYDKNISPRENILVSLGAVGEGFHNYHHSFPYDYSASEYRWHINFTTFFIDCMAAL
	GLAYDRKKVSKAAILARIKRTGDGNYXSG
	SEQ ID NO:43	1116 bp
NOV3n,	CCGGCCCACTTGCTGCAGGACGATATCTCTACCTCCTATACCACCACCACCACCATTACAGCGCCTC
CG105521-06
DNA Sequence	CCTCCAGGGTCCTGCAGAATGGAGGAGATAAGTTOGAGACGATGCCCCTCTACTTGGAAGACGACAT
	TCGCCCTGATATAAAAGATGATATATATGACCCCACCTACAAGGATAAGGAAGGCCCAAGCCCCAAG
	GTTGAATATGTCTGGAGAAACATCATCCTTATGTCTCTGCTACACTTGGGAGCCCTGTATGGGATCA
	CTTTGATTCCTACCTGCAAGTTCTACACCTGGCTTTGGGGGGTATTCTACTATTTTGTCAGTGCCCT
	GGGCATAACAGCAGGAGCTCATCGTCTGTCGAGCCACCGCTCTTACAAAGCTCCGCTGCCCCTACCG
	CTCTTTCTGATCATTGCCAACACAATGGCATTCCAGAATGATGTCTATGAATGGGCTCGTGACCACC
	GTGCCCACCACAAGTTTTCAGAAACACATGCTGATCCTCATAATTCCCGACGTGGCTTTTTCTTCTC
	TCACGTGGGTTGGCTGCTTGTGCGCAAACACCCAGCTGTCAAAGAGAAGGGGAGTACGCTAGACTTG
	TCTGACCTAGAAGCTGAGAAACTGGTGATGTTCCAGAGGAGGTACTACAAACCTGGCTTGCTGATGA
	TGTGCTTCATCCTGCCCACGCTTGTGCCCTGGTATTTCTGGGGTGAAACTTTTCAAAACAGTGTGTT
	CGTTGCCACTTTCTTGCGATATGCTGTGGTGCTTAATGCCACCTGGCTGGTGAACAGTGCTGCCCAC
	CTCTTCCGATATCGTCCTTATGACAAGAACATTAGCCCCCCGGAGAATATCCTGGTTTCACTTGGAG
	CTGTGGGTGAGGGCTTCCACAACTACCACCACTCCTTTCCCTATGACTACTCTCCCAGTGAGTACCG
	CTGGCACATCAACTTCACCACATTCTTCATTGATTGCATGGCCGCCCTCGGTCTGGCCTATGACCGG
	AAGAAAGTCTCCAAGGCCGCCATCTTGGCCAGGATTAAAAGAACCGGAGATGGAAACTACAAGAGTG
	GCTGAGCAGGTGCGGCCGCACTCGAGCACCACCACCACCACCAC
	ORF Start: at 1		ORF Stop: TGA at 1075
	SEQ ID NO:44	358 aa	MW at 41391.0kD
NOV3n,	PAHLLQDDISSSYTTTTTITAPPSRVLQNGGDKLETMPLYLEDDIRPDTKDDIYDPTYKDKEGPSPK
CG105521-06
Protein	VEYVWRNIILMSLLHLGALYGITLIPTCKFYTWLWGVFYYFVSALGITAGAHRLWSHRSYKARLPLR
Sequence
	LFLIIANTMAEQNDVYEWARDHRAHHKFSETHADPHNSRRGFFFSHVGWLLVRKHPAVKEKGSTLDL
	SDLEAEKLVMFQRRYYKPGLLMMCFILPTLVPWYFWGETFQNSVFVATFLRYAVVLNATWLVNSAAH
	LFGYRPYDKNISPRENTLVSLGAVGEGFHNYHHSFPYDYSASEYRWHINFTTFFIDCMAALGLAYDR
	KKVSKAAILARIKRTGDGNYKSG

[0364] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 3B.

TABLE 3B
Comparison of NOV3a against NOV3b through NOV3n.
			Identities/
			Similarities for
	Protein	NOV3a Residues/	the Matched
	Sequence	Match Residues	Region
	NOV3b	1 . . . 359	346/359 (96%)
		1 . . . 359	347/359 (96%)
	NOV3c	1 . . . 359	346/359 (96%)
		5 . . . 363	347/359 (96%)
	NOV3d	1 . . . 359	347/359 (96%)
		1 . . . 359	347/359 (96%)
	NOV3e	2 . . . 359	345/358 (96%)
		1 . . . 358	346/358 (96%)
	NOV3f	2 . . . 359	345/358 (96%)
		7 . . . 364	346/358 (96%)
	NOV3g	1 . . . 359	347/359 (96%)
		1 . . . 359	347/359 (96%)
	NOV3h	1 . . . 359	347/359 (96%)
		20 . . . 378	347/359 (96%)
	NOV3i	1 . . . 359	347/359 (96%)
		1 . . . 359	347/359 (96%)
	NOV3j	1 . . . 359	346/359 (96%)
		2 . . . 360	347/359 (96%)
	NOV3k	2 . . . 359	345/358 (96%)
		10 . . . 367	346/358 (96%)
	NOV3l	1 . . . 359	346/359 (96%)
		1 . . . 359	347/359 (96%)
	NOV3m	2 . . . 359	345/358 (96%)
		7 . . . 364	346/358 (96%)
	NOV3n	2 . . . 359	345/358 (96%)
		1 . . . 358	346/358 (96%)

[0365] Further analysis of the NOV3a protein yielded the following properties shown in Table 3C.

TABLE 3C
Protein Sequence Properties NOV3a
PSort     0.6000 probability located in plasma membrane;
analysis: 0.4000 probability located in Golgi body;
          0.3000 probability located in endoplasmic
          reticulum (membrane); 0.3000 probability located
          in microbody (peroxisome)
SignalP   No Known Signal Sequence Predicted
analysis:

[0366] 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 3D.

TABLE 3D
Geneseq Results for NOV3a
			Identities/
			Similarities for
Geneseq	Protein/Organism/Length	NOV3a Residues/	the Matched	Expect
Identifier	[Patent #, Date]	Match Residues	Region	Value
ABB44583	Human wound healing	1 . . . 359	359/359 (100%)	0.0
	related polypeptide SEQ ID	1 . . . 359	359/359 (100%)
	NO 40 - Homo sapiens, 359
	aa. [CA2325226-A1,
	17 MAY 2001]
AAY69378	Amino acid sequence of	1 . . . 359	359/359 (100%)	0.0
	human skin stearoyl-CoA	1 . . . 359	359/359 (100%)
	desaturase - Homo sapiens,
	359 aa. [WO200009754-A2,
	24 FEB. 2000]
AAY69377	Amino acid sequence of	1 . . . 359	298/359 (83%)	0.0
	murine skin stearoyl-CoA	1 . . . 359	334/359 (93%)
	desaturase (M-SCD4v1) -
	Mus sp, 359 aa.
	[WO200009754-A2,
	24 FEB. 2000]
ABB44582	Mouse wound healing related	1 . . . 359	297/359 (82%)	0.0
	polypeptide SEQ ID NO 39 -	1 . . . 358	327/359 (90%)
	Mus musculus, 358 aa.
	[CA2325226-A1,
	17 MAY 2001]
AAR25853	MSH-dependent protein obtd.	1 . . . 359	290/360 (80%)	e−179
	from hamster flank organ -	1 . . . 354	324/360 (89%)
	Mesocricetus auratus, 354 aa.
	[JP04179481-A,
	26 JUN. 1992]

[0367] 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 3E.

TABLE 3E
Public BLASTP Results for NOV3a
			Identities/
Protein			Similarities for
Accession		NOV3a Residues/	the Matched	Expect
Number	Protein/Organism/Length	Match Residues	Portion	Value
O00767	Acyl-CoA desaturase (EC	1 . . . 359	358/359 (99%)	0.0
	1.14.99.5) (Stearoyl-CoA	1 . . . 359	359/359 (99%)
	desaturase) (Fatty acid
	desaturase)
	(Delta(9)-desaturase) - Homo
	sapiens (Human), 359 aa.
Q9P1L1	Acyl-CoA desaturase (EC	38 . . . 359	321/322 (99%)	0.0
	1.14.99.5) (Stearoyl-CoA	1 . . . 322	322/322 (99%)
	desaturase) (Fatty acid
	desaturase)
	(Delta(9)-desaturase) - Homo
	sapiens (Human), 322 aa.
O62849	Acyl-CoA desaturase (EC	1 . . . 359	312/359 (86%)	0.0
	1.14.99.5) (Stearoyl-CoA	1 . . . 359	342/359 (94%)
	desaturase) (Fatty acid
	desaturase)
	(Delta(9)-desaturase) - Ovis
	aries (Sheep), 359 aa.
Q9BG81	Acyl-CoA desaturase (EC	1 . . . 359	312/359 (86%)	0.0
	1.14.99.5) (Stearoyl-CoA	1 . . . 359	342/359 (94%)
	desaturase) (Fatty acid
	desaturase)
	(Delta(9)-desaturase) - Capra
	hircus (Goat), 359 aa.
Q95MI7	Stearoyl coenzyme A	1 . . . 359	312/359 (86%)	0.0
	desaturase (EC 1.14.99.5) -	1 . . . 359	341/359 (94%)
	Capra hircus (Goat), 359 aa.

[0368] PFam analysis predicts that the NOV3a protein contains the domains shown in the Table 3F.

TABLE 3F
Domain Analysis of NOV3a
			Identities/
			Similarities for
	Pfam	NOV3a	the Matched	Expect
	Domain	Match Region	Region	Value
	Desaturase	77 . . . 321	154/248 (62%)	2.9e−164
			231/248 (93%)

Example 4

[0369]

TABLE 4A
NOV4 Sequence Analysis
	SEQ ID NO: 45	1346 bp
NOV4a,	TGGAACTCCAGGATACACTCCCCTCCTGCTACCTAGGCAGGCGTGAGGGTGTGACGGCCGCGCATTCG
CG107234-01
DNA Sequence	CCAGACGAGAGCG ATG CTGACAACGCCGCACCAGGTCTGATCTCAGAGCTGGGCTGGCTGTGCCCT
	GGGGCCACATCGCAGCCAAAGCCTGGGGCTCCCTGCACGGCCCTCCAGTTCTCTGCCTGCACGGCTGG
	CTGGACAATGCCAGCTCCTTCGACAGACTCATCCCTCTTCTCCCGCAAGACTTTTATTACGTTGCCAT
	GGATTTCGGAGGTCATGGGCTCTCGTCCCATTACAGCCCAGGTGTCCCATATTACCTCCAGACTTTTG
	TGAGTGAGATCCGAAGAGTTGTGGCAGCCTTGAAATGGAATCGATTCTCCATTCTGGGCCACAGCTTC
	GGTGGCGTCGTGGGCGGAATGTTTTTCTGTACCTTCCCCGAGATGGTGGATCCGATCTTATCTTGCTA
	CACGCCGCTCTTTCTCCTCGAATCAGATGAAATGGAGAACTTGCTGACCTACAGGCGGAGAGCCATAG
	AGCACGTCCTCCAGGTAGAGGCCTCCCAGGAGCCCTCGCACGTGTTCAGCCTGAAGCAGCTGCTGCAG
	AGGCAGAGAACAGCATTGACTTCGTCAGCAGGGAGCTGTGTGCGCATTCCATCATAGAGCTGCAGGCC
	CATGTCCTGTTGATCAAAGCAGTCCACGGATATTTTGATCCAAGAGAGAGATTACTCTGACGGGAGTC
	CCTGTCGTTCATGATAGACACAATGAATCCACCCTCAAGAGGACTACTTCGTAATACGTTCACAGCAA
	ACCCTGGCCTCGGCCCTGCCCTGTCCCTGCCATGCAACTTCACAACTCAGCTGGCCTAGACCCCTGGC
	AGGCCTCCAAGTCCCTAAGCGGTTCCAGTTTGTGGAAGTCCCAGGCAATCACTGTGTCCACATGAGCG
	AACCCCAGCACGTGGCCAGTATCATCAGCTCCTTCTTACAGTGCACACACACGCTCCCAGCCCAGCTG
	TAGCTCTGGGCCTGGAACTATGAAGACCTAGTGCTCCCAGACTCGACACTGGGACTCTGAGTGCCTGA
	GCCCCACAACAAGGCCAGGGATGGTGTGGACAGGCCTCACTAGTCTTGAGGCCCAGCCTAGGATGGTG
	GTCAGGGGAAGGAGCGAGATTCCAACTTCAACATCTGTGACCTCAAGGGGGAGACAGAGTCTGGGTTC
	CAGGGCTGCTGTCTCCTGGCTAATAATCTCCAGCCAGCTGGAGGAAGGAAGGGCGGGCTGGGCCCACC
	ORF Start: ATG at 82		ORF Stop: TGA at 691
	SEQ ID NO: 46	203 aa	MW at 22470.7kD
NOV4a,	MAENAAPGLISELKLAVPWGHIAAKAWGSLQGPPVLCLHGWLDNASSFDRLIPLLPQDFYYVAMDFGG
CG107234-01
Protein	HGLSSHYSPGVPYYLQTFVSEIRRVVAALKWNRFSILGHSFGGVVGGMFFCTFPEMVDKLILLDTPLF
Sequence
	LLESDEMENLLTYKRRAIEHVLQVEASQEPSHVFSLKQLLQRQRTALTSSAGSCVRIPSGSCRPMSC
	SEQ ID NO:47	937 bp
NOV4b,	CGGGACGAGAGCGATGAGTGAGAACGCCGCACCAGGTCTGATCTCAGAGCTGAAGCTGGCTGTGCCC
CG107234-03
DNA Sequence	TGGGGCCACATCGCAGCCAAAGCCTGGGGCTCCCTGCAGGGCCCTCCAGTTCTCTGCCTGCACGGCT
	GGCTGGACAATGCCAGCTCCTTCGACAGACTCATCCCTCTTCTCCCGCATGACTTTTATTACGTTGC
	CATGGATTTCGGAGGTCATGGGCTCTCGTCCCATTACAGCCCAGGTGTCCCATATTACCTCCAGACT
	TTTGTGAGTCACATCCGAAGAGTTGTGGCAGGTGGCGTCGTGGGCGGAGTGTTTTTCTGTACCTTCC
	CCGAGATGGTGGATAAACTTATCTTGCTGGACACGCCGCTCTTTCTCCTGGAATCAGATGAAATGGA
	GAATTGCTGACCTACAAGCGAGAGCCATAGAGCACGTGCTGCACGTAGAGTCCTCCCATTAGAGCCC
	TCGCACGTGTTCAGCCTGAAGCAGCTGCTGCAGAGGTTACTGAAGAGCAATAGCCACTTGAGTGAGG
	AGTGCGGGAGCTTCTCCTGCAAGAGAACCACGAAGGTGGCCACAGGTCTGGTTCTGTCGATCAGAGA
	CCAGAGGCTCGCCTGGGCAGAGAACACCATTGACTTCATCACCAGGGAGCTGTGTGCGCATTCCATC
	AGGAAGCTGCAGGCCCATGTCCTGTTGATCAAAGCAGTCCACGGATATTTTGATTCAAGACAGAATT
	ACTCTGAGAAGGAGTCCCTGTCGTTCATGATAGACACGATGAAATCCACCCTCAAAGAGCAGTTCCA
	GTTTGTGGAAGTCCCAGGCAATCACTGTGTCCACATGAGCGAACCCCAGCACGTGGCCAGTATCATC
	AGCTCCTTCTTACAGCGCACACACATGCTCCCAGCCCAGCTGTAGCTCTGGGCCTGGAACTATGAA
	ORF Start: ATG at 14		ORF Stop: TAG at 914
	SEQ ID NO: 48	300 aa	MW at 33777.6kD
NOV4b,	MSENAAPGLISELKLAVPWGHIAAKAWGSLQGPPVLCLHGWLDNASSFDRLIPLLPQDFYYVAMDFG
CG107234-03
Protein	GHGLSSHYSPGVPYYLQTFVSEIRRVVAGGVVGGMEFCTFPEMVDKLILLDTPLFLLESDEMEKLLT
Sequence
	YKRRAIEHVLQVEASQEPSHVFSLKQLLQRLLKSNSHLSEECGELLLQRGTTKVATGLVLNRDQRLA
	WAENSIDFISRELCAHSIRKLQAHVLLIKAVHGYFDSRQNYSEKESLSFMIDTMKSTLKEQFQFVEV
	PGNHCVHMSEPQHVASIISSFLQRTHMLPAQL
	SEQ ID NO: 49	1058 bp
NOV4c,	CGGGACGAGAGCG ATG AGTGAGAACGCCGCACCAGGTCTGATCTCAGAGCTGAAGCTGGCTGTGCCCT
CG107234-02
DNA Sequence	GGGGCCACATCGCAGCCAAAGCCTGGGGCTCCCTGCAGGGCCCTCCAGTTCTCTGCCTGCACGGCTGG
	CTGGACAATGCCAACTCCTTCGACAGACTCATCCCTCTTCTCCCGCAAGACTTTTATTACGTTGCCAT
	GGATTTCGGAGGTCATGGGCTCTCGTCCCATTACAGCCCAGGTGTCCCATATTACCTCCAGACTTTTG
	TGAGTGAGATCCGAAGAGTTGTGGCAGCCTTGAAATGGAATCGATTCTCCATTCTGGGCCACAGCTTC
	GGTGGCGTCCTGGGCGGAATGTTTTTCTGTACCTTCCCCGAGATGGTGGATAAACTTATCTTGCTGGA
	CACGCCGCTCTTTCTCCTGGAATCAGATGAAATGGAGAACTTGCTGACCTACAAGCGGAGAGCCATAG
	AGCACGTGCTGCAGGTAGAGGCCTCCCAGOAGCCCTCGCACGTGTTCAGCCTGAAGCAGCTGCTGCAG
	AGGTTACTGAAGAGCAATAGCCACTTGAGTGAGGAGTGCGGGGAGCTTCTCCTGCAAAGAGGAACCAC
	GAAGGTGGCCACAGAGATGGAGTTTCGCCATGTTGCCCAGGCTGGTCTCGAACTCCTGAACTCAAGCG
	ATCCTACTGACTCGACCTCCCAAAATGGTCTGGTTCTGAACAGAGACCAGAGGCTCGCCTGGGCAGAG
	AACAGCATTGACTTCATCAGCAGGGAGCTGTGTGCGCATTCCATCAGGAAGCTGCAGGCCCATGTCCT
	GTTGATCAAAGCAGTCCACGGATATTTTGATTCAAGACAGAATTACTCTGAGAAGGAGTCCCTGTCGT
	TCATGATAGACACGATGAAATCCACCCTCAAAGAGCAGTTCCAGTTTGTGGAAGTCCCAGGCAATCAC
	TGTGTCCACATGAGCGAACCCCAGCACGTGGCCAGTATCATCAGCTCCTTCTTACAGCGCACACACAT
	GCTCCCAGCCCAGCTGTAGCTCTGGGCCTGGAACTATG
	ORF Start: ATG at 14		ORF Stop: TAG at 1037
	SEQ ID NO: 50	341 aa	MW at 38407.6kD
NOV4c,	MSENAAPGLISELKLAVPWGHIAAKAWGSLQGPPVLCLHGWLDNANSFDRLIPLLPQDFYYVAMDFGG
CG107234-02
Protein	HGLSSHYSPGVPYYLQTFVSEIRRVVAALKWNRFSILGHSFGGVVGGMFFCTFPEMVDKLILLDTPLF
Sequence
	LLESDEMENLLTYKRRAIEHVLQVEASQEPSHVFSLKQLLQRLLKSNSHLSEECGELLLQRGTTKVAT
	EMEERHVAQAGLELLNSSDPTDSTSQNGLVLNRDQRLAWAENSIDFISRELCAHSIRKLQAHVLLIKA
	VHGYFDSRQNYSEKESLSFMIDTMKSTLKEQEQFVEVPGNHCVHMSEPQHXTASHSSFLQRTHMLPAQ
	L

[0370] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 4B.

TABLE 4B
Comparison of NOV4a against NOV4b and NOV4c.
			Identities/
			Similarities for
	Protein	NOV4a Residues/	the Matched
	Sequence	Match Residues	Region
	NOV4b	1 . . . 170	145/170 (85%)
		1 . . . 156	146/170 (85%)
	NOV4c	1 . . . 170	168/170 (98%)
		1 . . . 170	170/170 (99%)

[0371] Further analysis of the NOV4a protein yielded the following properties shown in Table 4C.

TABLE 4C
Protein Sequence Properties NOV4a
PSort     0.6072 probability located in microbody
analysis: (peroxisome); 0.4500 probability located
          in cytoplasm; 0.1930 probability located
          in lysosome (lumen); 0.1000 probability
          located in mitochondrial matrix space
SignalP   No Known Signal Sequence Predicted
analysis:

[0372] 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 4D.

TABLE 4D
Geneseq Results for NOV4a
			Identities/
			Similarities for
Geneseq	Protein/Organism/Length	NOV4a Residues/	the Matched	Expect
Identifier	[Patent #, Date]	Match Residues	Region	Value
AAY71117	Human Hydrolase protein-15	1 . . . 178	177/178 (99%)	e−102
	(HYDRL-15) - Homo	1 . . . 178	178/178 (99%)
	sapiens, 314 aa.
	[WO200028045-A2,
	18 MAY 2000]
AAU23386	Novel human enzyme	1 . . . 178	175/178 (98%)	e−100
	polypeptide #472 - Homo	10 . . . 187	176/178 (98%)
	sapiens, 323 aa.
	[WO200155301-A2,
	02 AUG. 2001]
AAM39135	Human polypeptide SEQ ID	1 . . . 98	94/98 (95%)	1e−51
	NO 2280 - Homo sapiens,	1 . . . 98	96/98 (97%)
	150 aa. [WO200153312-A1,
	26 JUL. 2001]
ABB60261	Drosophila melanogaster	12 . . . 132	58/122 (47%)	4e−28
	polypeptide SEQ ID NO 7575 -	41 . . . 162	77/122 (62%)
	Drosophila melanogaster,
	331 aa. [WO200171042-A2,
	27 SEP. 2001]
ABB68618	Drosophila melanogaster	12 . . . 177	61/171 (35%)	2e−27
	polypeptide SEQ ID NO	8 . . . 176	98/171 (56%)
	32646 - Drosophila
	melanogaster, 342 aa.
	[WO200171042-A2,
	27 SEP. 2001]

[0373] 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 4E.

TABLE 4E
Public BLASTP Results for NOV4a
			Identities/
Protein			Similarities for
Accession		NOV4a Residues/	the Matched	Expect
Number	Protein/Organism/Length	Match Residues	Portion	Value
Q9NQF3	Putative serine hydrolase-like	1 . . . 203	203/203 (100%)	e−117
	protein (EC 3.1.-.-) - Homo	1 . . . 203	203/203 (100%)
	sapiens (Human), 203 aa.
Q9H4I8	Serine hydrolase-like protein	1 . . . 178	177/178 (99%)	e−101
	(EC 3.1.-.-) - Homo sapiens	1 . . . 178	178/178 (99%)
	(Human), 314 aa.
Q9EPB5	Serine hydrolase-like protein	8 . . . 177	127/171 (74%)	1e−71
	(EC 3.1.-.-) (SHL) - Mus	2 . . . 172	145/171 (84%)
	musculus (Mouse), 311 aa.
BAC04444	CDNA FLJ37553 fis, clone	1 . . . 114	111/114 (97%)	2e−61
	BRCAN2028338, moderately	1 . . . 114	111/114 (97%)
	similar to Mus musculus
	serine hydrolase protein,
	isoform 2 - Homo sapiens
	(Human), 146 aa.
O18391	Probable serine hydrolase	12 . . . 132	58/122 (47%)	1e−27
	(EC 3.1.-.-) (Kraken protein) -	41 . . . 162	77/122 (62%)
	Drosophila melanogaster
	(Fruit fly), 331 aa.

[0374] PFam analysis predicts that the NOV4a protein contains the domains shown in the Table 4F.

TABLE 4F
Domain Analysis of NOV4a
		Identities/
		Similarities for
Pfam	NOV4a	the Matched	Expect
Domain	Match Region	Region	Value
No Significant Matches Found to Publically Available Domains

Example 5

[0375] 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:51	2109 bp
NOV5a,	CGCGCAGCCCGCCGGAGTGGTCGGGGCCCGCGGCCGCTCGCGCCTCTCGATGGGCAGCTCGCACTTGC
CG113144-01
DNA Sequence	TCAACAAGGGCCTGCCGCTTCGCGTCCGACCTCCGATCATGAACGGGCCCCTGCACCCGCGGCCCCTG
	GTGGCATTGCTGGATGGCCGGGACTGCACAGTGGAGATGCCCATCCTGAAGGACGTCCCCACTGTGGC
	CTTCTGCGACGCGCAGTCCACGCAGGAGATCCATGAGAAGGTCCTGAACGAGGCTGTGGGGGCCCTGA
	TGTACCACACCATCACTCTCACCACGGAGGACCTGGAGAAGTTCAAAGCCCTCCGCATCATCGTCCGG
	ATTCGCAGTGGTTTTGACAACATCGACATCAAGTCGGCCGGGGATTTAGGCATTGCCGTCTGCAACGT
	GCCCGCGGCGTCTGTGGAGGAGACGGCCGACTCGACCCTGTGCCACATCCTGAACCTGTACCGGCGGG
	CCACCTCGCTGCACCAGGCGCTGCGGGAGGGCACACGAGTCCAGAGCGTCGAGCAGATCCGCGAGGTG
	GCGTCCGGCGCTGCCAGGATCCGCGGGGAGACCTTGGGCATCATCCGACTTGGTCGCGTGGGGCAGGC
	AGTGGCGCTGCGGGCCAAGGCCTTCGGCTTCAACGTGCTCTTCTACGACCCTTACTTGTCGGATGGCG
	TGGAGCGGGCGCTGGGGCTGCAGCGTGTCAGCACCCTGCAGGACCTGCTCTTCCACAGCGACTGCGTG
	ACCCTGCACTGCGCCCTCAACGAGCACAACCACCACCTCATCAACGACTTCACCGTCAAGCAGATGAG
	ACAAGGGGCCTTCCTGGTGAACACAGCCCGGGGTGGCCTGGTGGATGAGAAGGCGCTGGCCCAGGCCC
	TGAAGGAGGGCCGGATCCCCGGCGCGGCCCTGGATGTGCACGAGTCCGAACCCTTCAGCTTTAGCCAG
	GGCCCTCTGAAGGATGCACCCAACCTCATCTGCACCCCCCATGCTGCATGGTACAGCGAGCAGGCATC
	CATCGAGATGCGAGAGGAGGCGGCACGGGAGATCCGCAGAGCCATCACAGGCCGGATCCCAGACAGCC
	TGAAGAACTGTGTCAACAAGGACCATCTGACAGCCGCCACCCACTGGGCCAGCATGGACCCCGCCGTC
	GTGCACCCTGAGCTCAATGGGGCTGCCTATAGGTACCCTCCGGGCGTGGTGGGCGTGGCCCCCACTGG
	CATCCCAGCTGCTGTGGAAGGTATCGTCCCCAGCGCCATGTCCCTGTCCCACGGCCTGCCCCCTGTGG
	CCCACCCGCCCCACGCCCCTTCTCCTGGCCAAACCGTCAAGCCCGAGGCGGATAGAGACCACGCCAGT
	GACCAGTTGTAGCCCGGGACGAGCTCTCCAGCCTCGGCGCCTGGGGCAGCGGGCCCGGAAACCCTCGA
	CCAGAGTGTGTGAGAGCATGTGTGTGGTGGCCCCTGTACACTGCAGAACTGGTCCGGGCTGTCAGGAG
	GGCGGGAGGGCGCAGCGCTGGGCCTCGTGTCGCTTGTCGTCCGTCCTGTGGGCGCTCTGCCCTGTGTC
	CTTCGCGTTCCTCGTTAAGCAGAAGAAGTCAGTAGTTATTCTCCCATGAACGTTCTTGTCTGTGTACA
	GTTTTTAGAACATTACAAAGGATCTGTTTGCTTAGCTGTCAACAAAAAGAAAACCTGAAGGAGCATTT
	GGAAGTCAATTTGAGGTTTTTTTTTTTGGTTTTTTTTTTTTTOTATTTTGGAACGTGCCCCAGAATGA
	GGCAGTTGGCAAACTTCTCAGGACAATGAATCTTCCCGTTTTTCTTTTTATGCCACACACTGCATTGT
	TTTTTCTACCTGCTTGTCTTATTTTTAGCATAATTTAGAAAAACAAAACAAAGGCTGTTTTTCCTAAT
	TTTGGCATCAACCCCCCCTTGTTCCAAAATGAAGACGGCATCATCACGAACCAGCTCCAAAAGGAAAA
	GCTTGGCAGGTGCCCTCGTCCTGGGGACGTGGAGGGTGGCACGCTCCCCGCCTGCACCAGTGCCGTCC
	TGCTGATGTGGTAGGCTAGCAATATTTTGGTTAAAATCATGTTTGTGGCCGAACGGGCCCCTGCACCC
	G
	ORF Start: ATG at 50		ORF Stop: TAG at 1370
	SEQ ID NO: 52	440 aa	MW at 47534.7kD
NOV5a,	MGSSHLLNXGLPLGVRPPINNGPLHPRPLVALLDGRDCTVEMPILKDVATVAFCDAQSTQEIHEKVLN
CG113144-01
Protein	EAVGALMYHTITLTREDLEKFKALRIIVRIGSGFDNIDIKSAGDLGIAVCNVPAASVEETADSTLCHI
Sequence
	LNLYRRATWLHQALREGTRVQSVEQIREVASGAARIRGETLGIIGLGRVGQAVALRAKAFGFNVLFYD
	PYLSDGVERALGLQRVSTLQDLLFHSDCVTLHCGLNEHNHHLINDFTVKQMRQGAFLVNTARGGLVDE
	KALAQALKEGRIRGAALDVHESEPFSFSQGPLKDAPNLICTPHAAWYSEQASIEMREEAAREIRRAIT
	GRIPDSLKNCVNKDHLTAATHWASMDPAVVHPELNGAAYRYPPGVVGVAPTGIPAAVEGIVPSAMSLS
	HGLPPVAHPPHAPSPGQTVKPEADRDHASDQL
	SEQ ID NO:53	2125 bp
NOV5b,	TATTAAGAGATGTCAGGCGTCCGACCTCCGATCATGAACGGGCCCCTGCACCCGCGGCCCCTGGTCG
CG113144-02
DNA Sequence	CATTGCTGGATGGCCGGGACTGCACAGTGGAGATGCCCATCCTGAAGGACGTGGCCACTGTGGCCTT
	CTGCGACGCGCAGTCCACGCAGCAGATCCATGAGAAGGTCCTGAACGAGGCTGTGGGGGCCCTGATG
	TACCACACCATCACTCTCACCAGGGAGGACCTGGACAAGTTCAAACCCCTCCGCATCATCGTCCGGA
	TTGGCAGTCGTTTTGACAACATCGACATCAAGTCGGCCGGGGATTTAGGCATTGCCGTCTGCAACGT
	GCCCGCGGCGTCTGTGGAGGAGACGGCCGACTCGACGCTGTGCCACATCCTGAACCTGTACCGGCGG
	GCCACCTCGCTGCACCAGCCGCTGCGGGAGGGCACACGAGTCCAGAGCGTCGAGCAGATCCGCGAGG
	TGGCCTCCGGCGCTGCCAGGATCCGCGGGGAGACCTTGCGCATCATCGGACTTCGTCCCGTGGCGCA
	GCCAGTGGCGCTGCGCGCCAAGGCCTTCGGCTTCAACGTGCTCTTCTACGACCCTTACTTGTCGGAT
	GGCGTGGAGCGGGCGCTGGGGCTGCAGCGTGTCAGCACCCTGCAGCACCTCCTCTTCCACACCGACT
	GCGTGACCCTGCACTCCGGCCTCAACGAGCACAACCACCACCTCATCAACGACTTCACCGTCAACCA
	GATGAGACAAGGGGCCTTCCTGGTGAACACAGCCCGGGGTGGCCTCGTCGATCAGAACCCGCTGGCC
	CAGGCCCTGAAGGAGGGCCGCATCCGCGGCGCGGCCCTGGATGTGCACGAGTCGGAACCCTTCAGCT
	TTAGCCAGGGCCCTCTGAAGGATGCACCCAACCTCATCTGCACCCCCCATCCTCCATCGTACACCGA
	GCAGCCATCCATCGAGATGCGAGAGGAGGCGGCACGGGAGATCCGCAGAGCCATCACAGGCCGGATC
	CCAGACAGCCTGAAGAACTGTGTCAACAAGGACCATCTGACAGCCGCCACCCACTCCGCCAGCATGC
	ACCCCCCCGTCGTGCACCCTGAGCTCAATGGCGCTGCCTATAGCAGGTACCCTCCGGGCGTGGTGGG
	CGTGGCCCCCACTGGCATCCCAGCTGCTGTGGAAGOTATCGTCCCCAGCGCCATGTCCCTCTCCCAC
	GGCCTGCCCCCTGTCGCCCACCCCCCCCACGCCCCTTCTCCTGCCCAAACCGTCAAGCCCGACGCGG
	ATAGAGACCACGCCAGTGACCAGTTGTAGCCCGGGAGGACCTCTCCAGCCTCGGCGCCTGGGCAGAG
	GGCCCGGAAACCCTCGGACCAGACTGTCTGCAGGAGGCATCTGTGTCCTGGCCCTGGCACTGCAGAC
	ACTCGTCCGGGCTGTCAGGAGGCGGGAGGGGGCAGCGCTGGGCCTCGTGTCGCTTGTCGTCGTCCGT
	CCTGTGGGCGCTCTGCCCTGTGTCCTTCGCGTTCCTCGTTAAGCACAAGAAGTCAGTAGTTATTCTC
	ACATGAACGTTCTTGTCTGTGTACACTTTTTAGAACATTACAAAGGATCTGTTTGCTTAGCTGTCAA
	CAAAAAGAAAACCTCAAGGAGCATTTGGAACTCAATTTCAGGTTTTTTTTTTTCGTTTTTTTTTTTT
	TGTATGTTGGAACCTCCCCCAGAATGAGGCAGTTGGCAAACTTCTCACCACAATCAATCCTTCCCGT
	TTTTCTTTTTATGCCACACAGTGCATTGTTTTTTCTACCTGCTTGTCTTATTTTTAGAATAATTTAC
	AAAAACAAAACAAAGGCTGTTTTTCCTAATTTTCGCATGAACCCCCCCTTGTTCCAAATGAAGACCG
	CATCATCACGAACCACCTCCAAAAGGAAAAGCTTGCGCGGTGCCCAGCGTGCCCGCTGCCCATCGAC
	GTCTGTCCTGGGGACGTGGAGGGTGGCAGCGTCCCCGCCTGCACCAGTGCCGTCCTCCTGATGTGGT
	AGGCTAGCAATATTTTCGTTAAAATCATGTTTGTCACTGTAACCATTTGTATGAATTATTTTAAAGA
	AATAAAAATCCTCGAAAGAGCCAGCGTGCCCACCAAAAAAAAAACCTC
	ORF Start: ATG at 10		ORF Stop: TAG at 1300
	SEQ ID NO: 54	430 aa	MW at 46491.5kD
NOV5b,	MSGVRPPIMNGPLHPRPLVALLDGRDCTVEMPILKDVATVAFCDAQSTQEIHEKVLNEAVGALMYHT
CG113144-02
Protein	ITLTREDLEKFKALRIIVRIGSGFDNIDIKSAGDLGIAVCNVPAASVEETADSTLCHILNLYRRATW
Sequence
	LHQALREGTRVQSVEQIREVASGAARIRGETLGITGLGRVGQAVALRAKAFGFNVLFYDPYLSDGVE
	RALGLQRVSTLQDLLFHSDCVTLHCGLNEHNHHLINDFTVKQMRQGAFLVNTARGGLVDEKALAQAL
	KEGRIRGAALDVHESEPFSFSQGPLKDAPNLICTPHAAWYSEQASIENREEAAREIRRAITGRIPDS
	PVAHPPHAPSPGQTVKPEADRDHASDQL
	SEQ ID NO:55	2085 bp
NOV5c,	GCGCAGGCCGCCGAGGGTCGGGGCCCGCGCCGGCTCGCGCCTCTCGATGGGCAGCTCGCACTTGCTCA
CG113144-03
DNA Sequence	ACAAGGGCCTGCCGCTTCGCGTCCGACCTCCGATCATGAACGGGCCCCTGCACCCGCGGCCCCTGGTG
	GCATTGCTGGATGGCCGGGACTGCACAGTGGAGATGCCCATCCTGAAGGACGTGGCCACTGTGGCCTT
	CTGCGACGCGCAGTCCACGCAGGAGATCCATGAGAAGGTCCTGAACGAGGCTGTGGGGGCCCTGATGT
	ACCACACCATCACTCTCACCAGGGAGGACCTGGAGAAGTTCAAAGCCCTCCGCATCATCGTCCGGATT
	GGCAGTGGTTTTGACAACATCGACATCAAGTCGGCCGGGGATTTAGGCATTGCCGTCTGCAACGTGCC
	CGCGGCGTCTGTGGAGGAGACGGCCGACTCGACGCTGTGCCACATCCTGAACCTGTACCGGCGGGCCA
	CTGGCTGCACCAGGCGCTGCGGGAGGGCACACGAGTCCAGAGCGTCGAGCAGATCCGCGAGGTGGCGT
	CCGCGCTGCCAGGATCCGCGGGGAGACCTTGGGCATCATCGGACTTGOTCGCGTGGGGCAGGCAGTGG
	CGCTGCGGGCCAACGTGTCGGCTTCAACCTGCTCTTCTACGACCCTTACTTGTCGGATGGCGTGGAGC
	GGGCGCTGGGGCTGCAGCGTGTCAGCACCCTGCAGGACCTGCTCTTCCACAGCGACTGCGTGACCCTG
	CACTGCGGCCTCAACGAGCACAACCACCACCTCATCAACGACTTCACCGTCAAGCAGATGAGACAAGG
	GGCCTTCCTGGTGAACACAGCCCGGGGTGGCCTGGTGGATGAGAAGGCGCTCCCCCAGGCCCTGAAGG
	AGGGCCGGATCCGCGGCGCGGCCCTGGATGTGCACGAGTCGGAACCCTTCAGCTTTAGCCAGGGCCCT
	CTGAAGGATGCACCCAACCTCATCTGCACCCCCCATGCTGCATGGTACAGCGAGCAGGCATCCATCGA
	GATGCGAGAGGAGGCGGCACGGGAGATCCGCAGAGCCATCACAGGCCGGATCCCAGACAGCCTGAAGA
	ACTGTGTCAACAAGGACCATCTGACAGCCGCCACCCACTGGGCCAGCATGGACCCCGCCGTCGTGCAC
	CCTGAGCTCAATGGGGCTCCCTATAGGTACCCTCCGGGCGTGGTGGGCGTGGCCCCCACTGGCATCCC
	AGCTGCTGTGGAAGGTATCGTCCCCAGCGCCATGTCCCTGTCCCACGGCCTGCCCCCTGTGGCCCACC
	CGCCCCACGCCCCTTCTCCTGGCCAAACCGTCAAGCCCGAGGCGGATAGAGACCACGCCAGTGACCAG
	TTGTAGCCCGGGAGGAGCTCTCCAGCCTCGGCGCCTGGGGCACCGGGCCCGGAAACCCTCCACCAGAG
	TGTGTGAGAGCATGTGTGTGGTGGCCCCTGGCACTGCAGAGACTGGTCCGGCCTGTCAGGAGGGCGGC
	AGGGCGCAGCGCTGGGCCTCGTGTCGCTTGTCGTCCGTCCTGTGGGCGCTCTGCCCTGTGTCCTTCGC
	GTTCCTCGTTAAGCAGAAGAAGTCAGTAGTTATTCTCCCATGAACGTTCTTGTCTGTGTACAGTTTTT
	ACAACATTACAAAGGATCTGTTTGCTTAGCTGTCAACAAAAAGAAAACCTGAAGGAGCATTTGGAAGT
	CAATTTGAGCTTTTTTTTTTTGGTTTTTTTTTTTTTGTATTTTGGAACGTGCCCCAGAATGAOGCAGT
	TGGCAAACTTCTCAGGACAATGAATCTTCCCGTTTTTCTTTTTATGCCACACAGTGCATTGTTTTTTC
	TACCTGCTTGTCTTATTTTTAGCATAATTTAGAAAAACAAAACAAAGGCTGTTTTTCCTAATTTTGGC
	ATGAACCCCCCCTTGTTCCAAAATGAAGACGGCATCATCACGAAGCAGCTCCAAAAGGAAAAGCTTGG
	CAGCTGCUCCTCGTCCTGGGGACGTGGAGGGTGGCACGGTCCCCGCCTGCACCAGTGCCGTCCTGCTG
	ATGTGGTAGGCTAGCAATATTTTGGTTAAAATCATGTTTGTGCCC
	ORF Start: ATG at 47		ORF Stop TAG at 1364
	SEQ ID NO: 56	439 aa	MW at 47552.4kD
NOV5c,	MGSSHLLNKGLPLGVRPPIMNGPLHPRPLVALLDGRDCTVEMPILKDVATVAFCDAQSTQEIHEKVLN
CG113144-03
Protein	EAVGALMYHTITLTREDLEKFKALRIIVRIGSGFDNIDIKSAGDLGIAVCNVPAASVEETADSTLCHI
Sequence
	LNLYRRATGCTRRCGRAHESRASSRSARWRPRCQDPRGDLGHBRTWSRGAGSGAAGQRVGFNVLFYDP
	YLSDGVERALGLQRVSTLQDLLFHSDCVTLHCGLNEHNUHLINDFTVKQMRQGAFLVNTARGGLVDEK
	ALAQALKEGRIRGAALDVHESEPFSFSQGPLKDAPNLICTPHAAWYSEQASIEHREEAAHEIRRAITG
	RIPDSLKNCVNKDHLTAATHWASHDFAVVHPELNGAAYRYPPGVVGVAPTGIPAAVEGIVPSAMSLSH
	GLPPVAHPPHAPSPGQTVKPEADRDHASDQL

[0376] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 5B.

TABLE 5B
Comparison of NOV5a against NOV5b and NOV5c.
			Identities/
			Similarities for
	Protein	NOV5a Residues/	the Matched
	Sequence	Match Residues	Region
	NOV5b	14 . . . 440	394/428 (92%)
		3 . . . 430	394/428 (92%)
	NOV5c	1 . . . 440	355/440 (80%)
		1 . . . 439	357/440 (80%)

[0377] Further analysis of the NOV5a protein yielded the following properties shown in Table 5C.

TABLE 5C
Protein Sequence Properties NOV5a
PSort     0.4500 probability located in cytoplasm; 0.3000
analysis: probability located in microbody (peroxisome);
          0.2559 probability located in lysosome (lumen);
          0.1000 probability located in mitochondrial
          matrix space
SignalP   No Known Signal Sequence Predicted
analysis:

[0378] 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 5D.

TABLE 5D
Geneseq Results for NOV5a
			Identities/
			Similarities for
Geneseq	Protein/Organism/Length	NOV5a Residues/	the Matched	Expect
Identifier	[Patent #, Date]	Match Residues	Region	Value
AAB12879	Murine JNK3 binding protein	14 . . . 440	421/428 (98%)	0.0
	amino acid sequence #5 -	3 . . . 430	424/428 (98%)
	Mus sp, 430 aa.
	[WO200031132-A1,
	02 JUN. 2000]
AAW42104	Amino acid sequence of the	1 . . . 440	396/447 (88%)	0.0
	Adenovirus E1A binding	1 . . . 439	403/447 (89%)
	protein (CtBP) - Homo
	sapiens, 439 aa.
	[US5773599-A,
	30 JUN. 1998]
AAB95805	Human protein sequence SEQ	74 . . . 439	288/366 (78%)	e−175
	ID NO: 18790 - Homo	1 . . . 366	329/366 (89%)
	sapiens, 366 aa.
	[EP1074617-A2,
	07 FEB. 2001]
ABB12442	Human bone marrow	99 . . . 439	252/342 (73%)	e−150
	expressed protein SEQ ID	1011 . . . 1352	292/342 (84%)
	NO: 281 - Homo sapiens,
	1352 aa. [WO200174836-A1,
	11 OCT. 2001]
ABB71579	Drosophila melanogaster	1 . . . 373	262/375 (69%)	e−150
	polypeptide SEQ ID NO	1 . . . 375	307/375 (81%)
	41529 - Drosophila
	melanogaster, 386 aa.
	[WO200171042-A2
	27 SEP. 2001]

[0379] 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 5E.

TABLE 5E
Public BLASTP Results for NOV5a
			Identities/
Protein			Similarities for
Accession		NOV5a Residues/	the Matched	Expect
Number	Protein/Organism/Length	Match Residues	Portion	Value
Q13363	C-terminal binding protein 1	1 . . . 440	440/440 (100%)	0.0
	(CtBP1) - Homo sapiens	1 . . . 440	440/440 (100%)
	(Human), 440 aa.
O88712	C-terminal binding protein 1	1 . . . 440	435/440 (98%)	0.0
	(CtBP1) - Mus musculus	1 . . . 440	437/440 (98%)
	(Mouse), 440 aa.
Q91WI6	C-terminal binding protein 1 -	1 . . . 440	435/441 (98%)	0.0
	Mus musculus (Mouse), 441	1 . . . 441	437/441 (98%)
	aa.
Q9YHU0	C-terminal binding protein	1 . . . 440	420/440 (95%)	0.0
	(CtBP) - Xenopus laevis	1 . . . 440	428/440 (96%)
	(African clawed frog), 440 aa.
Q91YX3	C-terminal binding protein 1 -	14 . . . 440	422/428 (98%)	0.0
	Mus musculus (Mouse), 430	3 . . . 430	424/428 (98%)
	aa.

[0380] PFam analysis predicts that the NOV5a protein contains the domains shown in the Table 5F.

TABLE 5F
Domain Analysis of NOV5a
		Identities/
		Similarities for
Pfam	NOV5a	the Matched	Expect
Domain	Match Region	Region	Value
2-Hacid_DH	28 . . . 122	28/104 (27%)	0.011
		65/104 (62%)
2-Hacid_DH_C	124 . . . 315	83/207 (40%)	3.6e−54
		145/207 (70%)

Example 6

[0381] 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:57	3657 bp
NOV6a,	GAGTCCCAGCCCCACGCCGGCTACCACCATGGCGGAGACCAACAACGAATGTAGCATCAAGGTGCTCT
CG122634-01
DNA Sequence	GCCGATTCCGGCCCCTGAACCAGGCTGAGATTCTGCGGGGAGACAAGTTCATCCCCATTTTCCAAGGG
	GACGACAGCGTCGTTATTGGGGGGAAGCCATATGTTTTTGACCGTGTATTCCCCCCAAACACGACTCA
	ACAAGCAAGTTTATCATGCATGTGCCATGCAGATTGTCAAAGATGTCCTTGTGGCTACAATGGCACCA
	TTTTTGCTTATGGACAGACATCCTCAGGGAAAACACATACCATGGAGGGAAAGCTGCACGACCCTCAG
	CTGATGGGAATCATTCCTCGAATTGCCCGAGACATCTTCAACCACATCTACTCCATGGATCACAACCT
	TGAGTTCCACATCAAGGTTTCTTACTTTGAAATTTACCTGGACAAAATTCCTGACCTTCTGCATGTGA
	CCAAGACAAATCTGTCCGTGCACGAGGACAAGAACCGGGTGCCATTTGTCAAGGGTTGTACTGAACGC
	TTTGTGTCCAGCCCGGAGGAGATTCTGGATGTGATTGATGAAGGGAAATCAAATCGTCATGTGGCTGT
	CACCAACATGAATGAACACAGCTCTCGGAGCCACAGCATCTTCCTCATCAACATCAAGCAGGAGAACA
	TGGAAACGGAGCAGAAGCTCAGTGGGAAGCTGTATCTGGTGGACCTGGCAGGGAGTGAGAAGGTCAGC
	AAGACTGGAGCACAGGGAGCCGTGCTGGACGAGGCAAAGAATATCAACAAGTCACTGTCAGCTCTGGG
	CAATGTGATCTCCGCACTGGCTGAGCGCACTAAAAGCTATGTTCCATATCGTGACAGCAAAATGACAA
	GGATTCTCCAGGACTCTCTCGCGGGAAACTGCCGGACGACTATGTTCATCTGTTGCTCACCATCCAGT
	TATAATGATGCAGAGACCAAGTCCACCCTGATGTTTGGGCAGCGGGCAAAGACCATTAAGAACACTGC
	CTCAGTAAATTTCGAGTTGACTGCTGAGCAGTGGAAGAAGAAATATGAGAAGGAGAAGGAGAAGACAA
	AGGCCCAGAAGGAGACGATTGCGAAGCTGGAGGCTGAGCTGAGCCGGTGGCGCAATGOAGAGAATGTG
	CCTGAGACAGAGCGCCTGGCTGGGGAGGAGGCAGCCCTGGGAGCCGAGCTCTGTGAGGAGACCCCTGT
	GAATGACAACTCATCCATCGTGGTGCGCATCGCGCCCGAGGAGCGGCAGAAATACGAGGAGGAGATCC
	GCCGTCTCTATAAGCAGCTTGACGACAAGGATGATGAAATCAACCAACAAAGCCAACTCATAGAGAAG
	CTCAAGCAGCAAATGCTGGACCAGGAAGAGCTGCTGGTGTCCACCCGAGGAGACAACGAGAAGGTCCA
	GCGGGAGCTGAGCCACCTGCAATCAGAGAACGATGCCGCTAAGGATGAGGTGAAGGAAGTGCTGCAGG
	CCCTGGAGGAGCTGGCTGTGAACTATGACCAGAAGTCCCAGGAGGTGGAGGAGAAGAGCCAGCAGAAC
	CAGCTTCTCGTGGATGAGCTGTCTCAGAAGGTGGCCACCATGCTGTCCCTGGAGTCTGAGTTGCAGCG
	GCTACAGGAGGTCAGTGGACACCAGCGAAAACGAATTGCTGAGGTGCTGAACGGGCTGATGAAGGATC
	TGAGCGAGTTCAGTGTCATTGTGGGCAACGGGGAGATTAAGCTGCCAGTGGAGATCAGTGGGGCCATC
	GAGGAGGAGTTCACTGTGGCCCGACTCTACATCAGCAAAATCAAATCAGAAGTCAAGTCTGTGGTCAA
	GCGGTGCCGGCAGCTGGAGAACCTCCAGGTGGAGTGTCACCGCAAGATGGAAGTGACCGGGCGGGAGC
	TCTCATCCTGCCAGCTCCTCATCTCTCAGCATGAGGCCAAGATCCCCTCGCTTACGGAATACATGCAG
	AGCGTGGAGCTAAAGAAGCGGCACCTGGAAGAGTCCTATGACTCCTTGAGCGATGACCTGGCCAAGCT
	CCAGGCCCAGGAAACTGTGCATGAAGTGGCCCTGAAGGACAAGGAGCCTGACACTCAGGATGCAGATG
	AAGTGAAGAAGGCTCTGGAGCTGCAGATGGAGAGTCACCGGGAGGCCCATCACCGGCAGCTGGCCCGG
	CTCCGGGACGAGATCAACGAGAAGCAGAAGACCATTGATGAGCTCAAAGACCTAAATCAGAAGCTCCA
	GTTAGAGCTAGAGAAGCTTCAGGCTGACTACGAGAAGCTGAAGAGCGAAGAACACGAGAAGAGCACCA
	AGCTGCAGGAGCTGACATTTCTGTACGAGCGACATGAGCAGTCCAAGCAGGACCTCAAGGGTCTGGAG
	GAGACAGTTGCCCGGGAACTCCAGACCCTCCACAACCTTCGCAAGCTGTTCGTTCAAGACGTCACGAC
	TCGAGTCAAGAAAAGTGCAGAAATGGAGCCCGAAGACAGTGGGGGGATTCACTCCCAAAAGCAGAACA
	TTTCCTTTCTTGAGAACAACCTGGAACAGCTTACAAAGGTTCACAAACAGCTGGTACGTGACAATGCA
	GATCTGCGTTGTCAGCTTCCTAAATTGGAAAAACGACTTAGGGCTACGGCTGAGAGAGTTAAGGCCCT
	GGAGGGTGCACTGAAGGAGGCCGTTCGCTACAAGAGCTCGGGCAAACGGGGCCATTCTGCCCAGATTG
	CCAAACCCGTCCGGCCTGGCCACTACCCAGCATCCTCACCCACCAACCCCTATGGCACCCGGAGCCCT
	GAGTGCATCAGTTACACCAACAGCCTCTTCCAGAACTACCAGAATCTCTACCTGCAGGCCACACCCAG
	CTCCACCTCAGATATGTACTTTGCAAACTCCTGTACCAGCACTGGAGCCACATCTTCTGGCGGCCCCT
	TGGCTTCCTACCAGAAGGCCAACATGGACAATGGAAATGCCACAGATATCAATGACAATAGGAGTGAC
	CTGCCGTGTCGCTATGAGGCTGAGGACCAGGCCAAGCTTTTCCCTCTCCACCAAGAGACAGCAGCCAG
	CTAATCTCCCACACCCACGGCTGCATACCTGCACTTTCAGTTTCTAAGAGGGACTGAGGCCTCTTCTC
	AGCATGCTGCAAACCTGTGGTCTCTGATACTAACTCCCTCCCCAACCCCTGTTGTTGGACTGTACTAT
	GTTTGATGTCTTCTCTTACTTACTCTGTATCTCTTTGTACTCTGTATCTATATATCAAAAGCTGCTGC
	TATGTCTCTCTTCTGTCTTATTCTCAAGTATCTACTGATGTATTTAGCAATTTCAAAGCATAGTCTAC
	CTTCCTTATTTGGGGCAATAGGGAGGAGGGTGAATGTTTCTTCTTTCTCATCTACTCGTCTCACACTG
	AGTGGTGTTAGTCACTGAGTAGAGGTCACAGAGATGACAAAAGGAAAAATGGGAGCTAGAGGGTTGTG
	ACCCTTCATACACACACGCACACACGCACACAAACATGCACACACGCATGCACACACACAAAGCCTTA
	AGCAGAAGAATGTCTTAGCATCATGAGACGAGAAATATACTCTTCCTCCCTCCTCTTTCACATATAGC
	ACAGAAGGTAAAATGGAACGGCTCCTAATTGAGACATATAATTTTCGCAATTC
	ORF Start: ATG at 29		ORF Stop: TAA at 3062
	SEQ ID NO:58	1011 aa	MW at 114816.1kD
NOV6a,	MAETNNECSIKVLCRFRPLNQAEILRGDKFTPIFQGDDSVVIGGKPYVFDRVFPPNTTQEQVYHACAM
CG122634-01
Protein	QIVKDVLAGYNGTIFAYGQTSSGKTHTMEGKLHDPQLMGIIPRIARDIFNHIYSHDENLEFHIKVSYF
Sequence
	EIYLDKIRDLLDVTKTNLSVHEDKNRVPFVKGCTERFVSSPEEILDVIDEGKSURHVAVTNNNEHSSR
	SHSIFLINIKQENMETEQKLSGKLYLVDLACSEKVSKTGAEGAVLDFAKNINKSLSALGNVISALAEG
	TKSYVPYRDSKHTRILQDSLGGNCRTTMFICCSPSSYNDAETKSTLHFGQRAKTIKNTASVNLELTAE
	QWKKKYEKEKEKTKAQKETIAXLEAELSRWRNGENVPETERLAGEEAALGAELCEETPVNDNSSIVVR
	IAPEERQKYEEEIRRLYKQLDDKDDEINQQSQLIEKLKQQMLDQEELLVSTRGDNEKVQRELSHLQSE
	NDAAKDEVKEVLQALEELAVNYDQKSQEVEEKSQQNQLLVDELSQKVATMLSLESELQRLQEVSGHQR
	KRIAEVLNGLHKDLSEFSVIVGNGEIKLPVEISGAIEEEFTVARLYISKHISEVKSVVKRCRQLENLQ
	VECHRKMEVTGRELSSCQLLISQHEAKIRSLTEYMQSVELKKRHLEESYDSLSDELAKLQAQETVHEV
	ALKDKEPDTQDADEXTKKALELQMESHREAHHRQLARLRDEINEKQKTIDELKDLNQKLQLLEKLQAD
	YEKLKSEEHEKSTKLQELTFLYERHEQSKQDLKGLEETVARELQTLHNLRKLFVQDVTTRVKKSAEME
	PEDSGGTHSQKQKISFLENNLEQLTKVHKQLVRDNADLRCELPKLEKRLRATAERVKALEGALKEAVR
	YKSSGKRGHSAOIAKPVRPGHYPASSPTNPYGTRSPECISYTNSLFONYONLYLOATPSSTSDMYFAN
	SCTSSGATSSGGPLASYQKANMDNGNATDINDNRSDLPCGYEAEDQAKLFPLHQETAAS

[0382] Further analysis of the NOV6a protein yielded the following properties shown in Table 6B.

TABLE 6B
Protein Sequence Properties NOV6a
PSort     0.4379 probability located in mitochondrial
analysis: matrix space; 0.3000 probability located in
          microbody (peroxisome); 0.3000 probability
          located in nucleus; 0.1217 probability located
          in mitochondrial inner membrane
SignalP   No Known Signal Sequence Predicted
analysis:

[0383] 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
			Identities/
			Similarities for
Geneseq	Protein/Organism/Length	NOV6a Residues/	the Matched	Expect
Identifier	[Patent #, Date]	Match Residues	Region	Value
AAM78880	Human protein SEQ ID NO	7 . . . 918	661/939 (70%)	0.0
	1542 - Homo sapiens, 963 aa.	6 . . . 941	787/939 (83%)
	[WO200157190-A2,
	09 AUG. 2001]
AAM79864	Human protein SEQ ID NO	7 . . . 918	654/940 (69%)	0.0
	3510 - Homo sapiens, 979 aa.	21 . . . 957	780/940 (82%)
	[WO200157190-A2,
	09 AUG. 2001]
ABB63485	Drosophila melanogaster	7 . . . 904	551/946 (58%)	0.0
	polypeptide SEQ ID NO	10 . . . 949	699/946 (73%)
	17247 - Drosophila
	melanogaster, 975 aa.
	[WO200171042-A2,
	27 SEP. 2001]
AAW72746	Drosophila kinesin -	7 . . . 904	550/946 (58%)	0.0
	Drosophila sp, 975 aa.	10 . . . 949	698/946 (73%)
	[US5830659-A,
	03-NOV-1998]
AAW72745	Drosophila kinesin	7 . . . 386	273/383 (71%)	e−159
	N-terminal 411 amino acid	10 . . . 392	322/383 (83%)
	residues - Drosophila sp, 411
	aa. [US5830659-A,
	03 NOV. 1998]

[0384] 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
			Identities/
Protein			Similarities for
Accession		NOV6a Residues/	the Matched	Expect
Number	Protein/Organism/Length	Match Residues	Portion	Value
Q12840	Neuronal kinesin heavy chain	1 . . . 1011	1010/1032 (97%)	0.0
	(NKHC) (Kinesin heavy chain	1 . . . 1032	1010/1032 (97%)
	isoform 5A) (Kinesin heavy chain
	neuron-specific 1) -
	Homo sapiens (Human), 1032
	aa.
P33175	Neuronal kinesin heavy chain	1 . . . 1011	983/1032 (95%)	0.0
	(NKHC) (Kinesin heavy chain	1 . . . 1027	999/1032 (96%)
	isoform 5A) (Kinesin heavy
	chain neuron-specific 1) -
	Mus musculus (Mouse), 1027
	aa.
S37711	kinesin heavy chain - mouse,	7 . . . 1011	956/1027 (93%)	0.0
	1027 aa.	6 . . . 1027	987/1027 (96%)
O60282	Kinesin heavy chain isoform	7 . . . 918	699/939 (74%)	0.0
	5C (Kinesin heavy chain	6 . . . 943	806/939 (85%)
	neuron-specific 2) - Homo
	sapiens (Human), 957 aa.
P28738	Kinesin heavy chain isoform	7 . . . 918	695/938 (74%)	0.0
	5C (Kinesin heavy chain	6 . . . 942	803/938 (85%)
	neuron-specific 2) - Mus
	musculus (Mouse), 956 aa.

[0385] PFam analysis predicts that the NOV6a protein contains the domains shown in the Table 6E.

TABLE 6E
Domain Analysis of NOV6a
		Identities/
		Similarities for
Pfam	NOV6a	the Matched	Expect
Domain	Match Region	Region	Value
kinesin	15 . . . 357	178/417 (43%)	8.4e−174
		299/417 (72%)
Phosphoprotein	482 . . . 507	7/26 (27%)	0.77
		20/26 (77%)

Example 7

[0386] 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: 59	701 bp
NOV7a,	GCGGTGTATGTGCGGCAATAACATGTCAACCCCOCTGCCCACCATCGTGCCCGCCCCCCGGAAGGCCA
CG125197-01
DNA Sequence	CCACTGAGGTGATTTTCCTGCATGGATTGGGAGATACTGGGCACGGATGGGCAGAAGccTTTGCCGGT
	ATCATAAGTTCACATATCAAATATATCTGCCCGCATGCGCCTGTTAGGCCTGTTACATTAAATATGAA
	CATAGCTATGCCTTCATGGTTTGATATTATTGGGCTTTCACCAGATTCACAGGAGGATGAATCTGGGA
	TTAAACAGGCAGCACAAAATATAAAAGCTTTGATTGATCAAGAAGTGAAGAATGGCATTCCTTCTAAC
	AGAATTATTTTGGGAGGGTTTTCTCAGGGAGGAGCTTTATCTTTATATACTGCCCTTACCACGCACCA
	GAAACTGGCAGGTGTCACTGCACTCAATTGCTGGCTTCCACTTTGGGCTTCCTTTCCACAGGGTCCTA
	TCGGTGGTGCTAATAGAGATATTTCTATTCTCCAGTGCCACGGGGATTGTGACCCTTTGGTTCCCCTG
	ATGTTTGGTTCTCTTACGGTTGAAAAACTAAAAACATTGGTGAATCCACCCAATGTGACCTTTAAAAC
	CTATGAAGGTATGATGCACAGTTCGTGTCAACAGGAAATGATGAATGTCAAGCAATTCATTGATAAAC
	TCCTACCTCCAATTGATTGAC
	ORF Start: ATG at 8	ORF Stop: TGA at 698
	SEQ ID NO: 60	230 aa	MW at 24848.5kD
NOV7a,	MCGNNMSTPLPTIVPAPRKATTEVIFLHGLGDTGHGWAEAFAGIISSHIKYICPHAPVRPVTLNMNIA
CG125197-01
Protein	MPSWFDIIGLSPDSQEDESGIKQAAQNIKALIDQEVKNGIPSNRIILGGFSQGGALSLYTALTTHQKL
Sequence	AGVTALNCWLPLWASFPQGPIGGANRDISILQCHGDCDPLVPLMFGSLTVEKLKTLVNPANVTFKTYE
	GMMHSSCQQEMNVKQFIDKLLPPID
	SEQ ID NO: 61	616 bp
NOV7b,	TGTGAGCTGAGGCGGTGTATGTGCGGCAATAACATGTCAACCCCGCTGCCCGCCATCGTGCCCGCCG
CG125197-03
DNA Sequence	CCCGGAAGGCCACCGCTCCGGTGATTTTCCTGCATGGGTTGGGAGATACTGGGCACGGATOGGCAGA
	AGCCTTTGCAGGTATCAGAAGTTCACATATCAAATATATCTGCCCGCATGCGCCTGTTAGGCCTGTT
	ACATTAAATATGAACGTGGCTATGCCTTCATGGTTTGATATTATTGGGCTTTCACCAGATTCACAGG
	AGGATGAATCTGGGATTAAACAGGCAGCAGAAAATATAAAAGCTTTGATTGATCAAGAAGTGAAGAA
	TGGCATTCCTTCTAACAGAATTATTTTGGCAGGGTTTTCTCAGTGCCACGGGGATTGTGACCCTTTG
	GTTCCCCTGATGTTTGGTCCTCTTACGGTGGAAAAACTAAAAACATTGGTGAATCCAGCCAATGTGA
	CCTTTAAAACCTATGAAGGTATGATGCACAGTTCGTGTCAACACGAAATGATGGATGTCAAGCAATT
	CATTGATAAACTCCTACCTCCAATTGATTGACGTCACTAAGAGGCCTTGTGTAGAAGTACACCAGCA
	TCATTGTAGTAGA
	ORF Start: ATG at 19	ORF Stop: TGA at 565
	SEQ ID NO: 62	182 aa	MW at 19740.7kD
NOV7b,	MCGNNMSTPLPAIVPAARKATAAVIFLHGLGDTGHGWAEAFAGIRSSHIKYICPHAPVRPVTLNMNV
CG125197-03
Protein	AMPSWFDIIGLSPDSQEDESGIKQAAENIKALIDQEVKNGIPSNRIILGGFSQCHGDCDPLVPLMFG
Sequence
	PLTVEKLKTLVNPANVTFKTYEGMMHSSCQQEMMDVKQFIDKLLPPID
	SEQ ID NO: 63	1486 bp
NOV7c,	AGCCGCTCGCACGCCCTTGGGCCGCGGCCGGGCGCCCGCTCTTCCTTCCGCTTGCGCTGTGAGCTGAG
CG125197-02
DNA Sequence	GCGGTGTATGTGCGGCAATAACATGTCAACCCCGCTGCCCGCCATCGTGCCCGCCGCCCGGAAGGCCA
	CCGCTGCGGTGATTTTCCTGCATGGATTGGGAGATACTGGGCACGGATGGGCAGAAGCCTTTGCAGGT
	ATCAGAAGTTCACATATCAAATATATCTGCCCGCATGCGCCTGTTACGCCTGTTACATTAAATATGAA
	CGTGGCTATGCCTTCATGGTTTGATATTATTGGGCTTTCACCAGATTCACAGGAGGATGAATCTGGGA
	TTAAACAGGCAGCAGAAAATATAAAAGCTTTGATTGATCAAGAAGTGAAGAATGGCATTCCTTCTAAC
	AGAATTATTTTGGGAGGGTTTTCTCAGGGAGGAGCTTTATCTTTATATACTGCCCTTACCACACAGCA
	GAAACTCGCAGGTGTCACTGCACTCAGTTGCTGGCTTCCACTTCGGGCTTCCTTTCCACAGGGTCCTA
	TCGGTGGTGCTAATAGAGATATTTCTATTCTCCAGTGCCACGCGGATTGTGACCCTTTGGTTCCCCTG
	ATGTTTGGTTCTCTTACGGTCGAAAAACTAAAAACATTGGTGAATCCAGCCAATGTGACCTTTAAAAC
	CTATGAAGGTATGATGCACAGTTCGTGTCAACAGGAAATGATGGATGTCAAGCAATTCATTGATAAAC
	TCCTACCTCCAATTGATTGACGTCACTAAGAGGCCTTGTGTAGAAGTACACCAGCATCATTGTAGTAG
	AGTGTAAACCTTTTCCCATGCCCAGTCTTCAAATTTCTAATGTTTTGCAGTGTTAAAATGTTTTGCAA
	ATACATGCCAATAACACAGATCAAATAATATCTCCTCATGAGAAATTTATGATCTTTTAAGTTTCTAT
	ACATGTATTCTTATAAGACGACCCAGGATCTACTATATTAGAATAGATGAAGCAGGTAGCTTCTTTTT
	TCTCAAATGTAATTCAGCAAAATAATACAGTACTGCCACCAGATTTTTTATTACATCATTTGAAAATT
	AGCAGTATCCTTAATGAAAATTTGTTCAGGTATAAATGAGCAGTTAAGATATAAACAATTTATGCATG
	CTGTGACTTAGTCTATGGATTTATTCCAAAATTGCTTAGTCACCATGCAGTGTCTGTATTTTTATATA
	TGTGTTCATATATACATAATGATTATAATACATAATAAGAATGACGTGGTATTACATTATCCCTAATA
	ATAGGGATAATGCTGNTTATTGTCCAGGAAAAAGTAAAATCGGTCCCCTTCAATTAATGGCCCTTTTA
	ATNTNGGGACCAGGCTTTTAATTTTCCCCGGATATTAATTTCCAATTTAATACCCCTTTCCNCNCCAG
	AAAAAAAAAAAAAGTTTGTTTTTTCCTTAATTGTCTTCATAGCAGGCCAAGTATTGCC
	ORF Start: ATG at 76	ORF Stop: TGA at 766
	SEQ ID NO: 64	230 aa	MW at 24669.3kD
NOV7c,	MCGNNMSTPLPAIVPAARKATAAVIFLHGLGDTGHGWAEAFAGIRSSHIKYICPHAPVRPVTLNMNVA
CG125197-02
Protein	MPSWFDIIGLSPDSQEDESGIKQAAENIKALIDQEVKNGIPSNRIILGGFSQGGALSLYTALTTQQKL
Sequence
	AGVTALSCWLPLRASFPQGPIGGANRDISILQCHGDCDPLVPLMFGSLTVEKLKTLVNPANVTFKTYE
	GMMHSSCQQEMMDVKQFIDKLLPPID

[0387] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 7B.

TABLE 7B
Comparison of NOV7a against NOV7b and NOV7c.
			Identities/
		NOV7a Residues/	Similarities for
	Protein Sequence	Match Residues	the Matched Region
	NOV7b	1 . . . 230	173/230 (75%)
		1 . . . 182	176/230 (76%)
	NOV7c	1 . . . 230	219/230 (95%)
		1 . . . 230	223/230 (96%)

[0388] Further analysis of the NOV7a protein yielded the following properties shown in Table 7C.

TABLE 7C
Protein Sequence Properties NOV7a
PSort analysis:   0.6500 probability located in cytoplasm; 0.2605
                  probability located in lysosome (lumen); 0.1000
                  probability located in mitochondrial matrix space;
                  0.0000 probability located in endoplasmic reticulum
                  (membrane)
SignalP analysis: No Known Signal Sequence Predicted

[0389] 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 7D.

TABLE 7D
Geneseq Results for NOV7a
		NOV7a	Identities/
		Residues/	Similarities
Geneseq	Protein/Organism/Length	Match	for the	Expect
Identifier	[Patent #, Date]	Residues	Matched Region	Value
AAU85134	Human lysophospholipase I	1 . . . 230	219/230 (95%)	e−128
	#2 - Homo sapiens, 230 aa.	1 . . . 230	223/230 (96%)
	[WO200210185-A1,
	07 FEB. 2002]
AAU85132	Human lysophospholipase I	1 . . . 230	219/230 (95%)	e−128
	#1 - Homo sapiens, 230 aa.	1 . . . 230	223/230 (96%)
	[WO200210185-A1,
	07 FEB. 2002]
ABG07277	Novel human diagnostic	1 . . . 230	219/230 (95%)	e−128
	protein #7268 - Homo	46 . . . 275	223/230 (96%)
	sapiens, 275 aa.
	[WO200175067-A2,
	11 OCT. 2001]
AAB53451	Human colon cancer antigen	1 . . . 230	219/230 (95%)	e−128
	protein sequence SEQ ID	34 . . . 263	223/230 (96%)
	NO: 991 - Homo sapiens, 263
	aa. [WO200055351-A1,
	21 SEP. 2000]
AAY09531	Human lysophospholipase	1 . . . 230	219/230 (95%)	e−128
	extended NHLP - Homo	1 . . . 230	223/230 (96%)
	sapiens, 230 aa.
	[WO9849319-A1,
	05 NOV. 1998]

[0390] 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 7E.

TABLE 7E
Public BLASTP Results for NOV7a
		NOV7a	Identities/
Protein		Residues/	Similarities
Accession		Match	for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
O75608	Lysophospholipase	1 . . . 230	219/230 (95%)	e−127
	(Acyl-protein thioesterase-1)	1 . . . 230	223/230 (96%)
	(Lysophospholipase I) - Homo
	sapiens (Human), 230 aa.
O77821	Calcium-independent	1 . . . 230	202/230 (87%)	e−119
	phospholipase A2 isoform 2 -	1 . . . 230	213/230 (91%)
	Oryctolagus cuniculus
	(Rabbit), 230 aa.
P70470	LYSOPHOSPHOLIPASE -	1 . . . 230	203/230 (88%)	e−118
	Rattus norvegicus(Rat), 230	1 . . . 230	213/230 (92%)
	aa.
O77820	Calcium-independent	14 . . . 230	202/217 (93%)	e−116
	phospholipase A2 isoform 1 -	3 . . . 219	207/217 (95%)
	Oryctolagus cuniculus
	(Rabbit), 219 aa (fragment).
Q9UQF9	Lysophospholipase isoform -	1 . . . 230	204/230 (88%)	e−114
	Homo sapiens (Human), 214	1 . . . 214	207/230 (89%)
	aa.

[0391] PFam analysis predicts that the NOV7a protein contains the domains shown in the Table 7F.

TABLE 7F
Domain Analysis of NOV7a
		Identities/
	NOV7a	Similarities
	Match	for the	Expect
Pfam Domain	Region	Matched Region	Value
abhydrolase_2	10 . . . 226	123/236 (52%)	1.3e−108
		193/236 (82%)

Example 8

[0392] 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: 65	3515 bp
NOV8a,	AAAGGGGAGTCCGGTGAACGGGCAGAAGCAGGGCCATGCCCAAGCCACCCCCAAGATCCCCCTGAACC
CG125312-01
DNA Sequence	TGCACCTCCATCACGACCCATTCAGGAGCCTCCAGGAGCCCAGACACCAGCCCCCCACCATGGGCAGC
	AAGGAGCGCTTCCACTGGCAGAGCCACAACGTGAAGCAGAGCGGCGTGGATGACATGGTGCTTCTTCC
	CCAGATCACCGAAGACGCCATTGCCGCCAACCTCCGGAAGCGCTTCATGGACGACTACATCTTCACCT
	ACATCGGCTCTGTGCTCATCTCTGTAAACCCCTTCAAGCAGATGCCCTACTTCACCGACCGTGAGATC
	GACCTCTATCAGGGCGCGGTGCAGTATGAGAATCCCCCGCACATCTACGCCCTCACGGACAACATGTA
	CCGGAACATGCTTATCGACTGTGAGAACCAGTGTGTCATCATTAGTCGAGAGAGTGGAGCTGGGAAGA
	CAGTGGCAGCCAAATATATCATGGGCTACATCTCCAAGGTGTCTGGCGGAGGCGAGAAGGTCCAGCAC
	GTCAAAGATATCATCCTGCAGTCCAACCCGCTGCTCGAGGCCTTCGGCAACGCCAAGACTGTGCGCAA
	CAACAATTCCAGCCGCTTTGGCAAGTACTTTGAGATCCAGTTCAGCCGAGGTGGGGAGCCAGATGGGG
	GCAAGATCTCCAACTTCTTGCTGGAGAAGTCCCGCGTGGTCATCCAAAATGAAAATGAGAGGAACTTC
	CACATCTACTACCAGCTGCTGGAAGGGGCCTCCCAGGAGCAAAGGCAGAACCTGGGCCTCATGACACC
	GGACTACTATTACTACCTCAACCAATCGGACACCTACCAGGTGGACGGCACGGACGACAGAAGCGACT
	TTGGTGAGACTCTGAGTGCTATGCAGGTTATTGGGATCCCGCCCAGCATCCAGCAGCTGGTCCTGCAG
	CTCGTGGCCGGCATCTTGCACCTGGGGAACATCAGTTTCTGTGAAGACGGGAATTACGCCCGAGTGGA
	GAGTGTGGACCTGGCCTTTCCCGCCTACCTGCTGGGCATTGACAGCGGGCGACTGCAGGAGAAGCTGA
	CCAGCCGCAAGATGGACAGCCCCTCGGGCCGGCGCAGCGAGTCCATCAATGTGACCCTCAACGTGGAG
	CAGGCAGCCTACACCCGTGATGCCCTGGCCAAGGGGCTCTATGCCCGCCTCTTCGACTTCCTCGTGGA
	GGCGATCAACCGTGCTATGCAGAAACCCCAGGAAGAGTACAGCATCGGTGTGCTGGACATTTACGGCT
	TCGAGATCTTCCAGAAAAATGGCTTCGAGCAGTTTTGCATCAACTTCGTCAATGAGAAGCTGCAGCAA
	ATCTTTATCGAACTTACCCTGAAGGCCGAGCAGGAGGAGTATGTGCAGGAAGGCATCCGCTGGACTCC
	AATCCAGTACTTCAACAACAAGGTCGTCTGTGACCTCATCGAAAACAAGCTGAGCCCCCCAGGCATCA
	TGAGCGTCTTGGACGACGTGTGCGCCACCATCCACGCCACGCGCCGGGGAGCAGACCAGACACTGCTG
	CAGAAGCTGCAGGCGGCTGTGGGGACCCACGAGCATTTCAACAGCTGGAGCGCCGGCTTCGTCATCCA
	CCACTACGCTGGCAAGGTGTCCTACGACGTCAGCGGCTTCTGCCAGAGGAACCGAGACGTTCTCTTCT
	CCGACCTCATAGAGCTGATGCAGACCAGTGAGCAGTTCCTCCGGATGCTCTTCCCCGAGAAGCTGGAT
	GGAGACAAGAAGGGGCGCCCCAGCACCGCCGGCTCCAAGATCAAGAAACAAGCCAACGACCTGGTGGC
	CACACTGATGACGTGCACACCCCACTACATCCGCTGCATCAAACCCAACGAGACCAAGAGGCCCCGAG
	ACTGGGAGGAGAACAGGGTCAAGCACCAGGTGGAATACCTGGGCCTGAAGGAGAACATCAGGGTGCGC
	AGAGCCGGCTTCGCCTACCGCCGCCAGTTCGCCAAATTCCTGCAGACGTATGCCATTCTGACCCCCGA
	GACGTGGCCGCGGTGGCGTGGGGACGAACCCCAGGGCGTCCAGCACCAGCTTCGGGCGGTCAACATGG
	AGCCCGACCAGTACCAGATGGGGAGCACCAAGGTCTTTGTCAAGAACCCAGAGTCGCTTTTCCTCCTG
	GAGGAGGTGCGACAGCGAAAGTTCGATCGCTTTGCCCGAACCATCCAGAAGGCCTGGCGGCGCCACGT
	GGCTGTCCGOAAGTACGAGGAGATGCGGGAGGAAGCTTCCAACATCCTGCTGAACAAGAAGGAGCGGA
	GGCGCAACAGCATCAATCGGAACTTCGTCCGGGACTACCTGGGGCTGGACGAGCGGCCCGAGCTGCGT
	CAGTTCCTGGGCAAGAGGGAGCGGGTGGACTTCGCCGATTCGGTCACCAAGTACGACCGCCGCTTCAA
	GCCCATCAAGCGGGACTTGATCCTGACGCCCAAGTGTGTGTATGTGATTGGGCGAGAGAAAGTGAAGA
	AGGGACCTGACAAGGGCCAGGTGTGTGAAGTCTTGAAGAAGAAAGTGGACATCCAGGCTCTGCGGGGA
	GTCTCCCTCAGCACGCGACAGGACGACTTCTTCATCCTCCAAGAGGATGCCGCCGACAGCTTCCTGGA
	GAGCGTCTTCAAGACCGAGTTTGTCAGCCTTCTGTGCAAGCGCTTCGAGGAGGCGACGCGGAGGCCCC
	TGCCCCTCACCTTCAGCGACAGACTACAGTTTCGGGTGAAGAAGGAGGCCTGGGGCGGTGGCGGCACC
	CGCAGCGTCACCTTCTCCCGCGGCTTCGGCGACTTGGCAGTGCTCAAGGTTGGCGGTCGGACCCTCAC
	GGTCAGCGTGGGCCATGGGCTGCCCAAGAGCTCAGAGCCTACGCGGAAGCGAATCGCCAAGGGAAAAC
	CTCGGAGGTCGTCCCAAGCCCCTACCCGGGCGGCCCCTGCGCCCCCCAGAGGTATGGATCGCAATGGG
	GTGCCCCCCTCTGCCAGAGGGGGCCCCCTGCCCCTGGAGATCATGTCTGGAGGGGGCACCCACAGGCC
	TCCCCGGGGCCCTCCGTCCACATCCCTGGGAGCCAGCAGACGACCCCGGGCACGTCCGCCCTCAGAGC
	ACAACACAGAATTCCTCAACGTGCCTGACCAGGGCATGGCCGGGATGCAGAGGAACCCCACCGTGGGG
	CAACGGCCAGTGCCTGGTGTGGGCCGACCCAAGCCCCACCCTCGGACACATGGTCCCAGGTGCCGGGC
	CCTATACCAGTACGTGGGCCAAGATGTGGACGAGCTGAGCTTCAACGTGAACCAGGTCATTGAGATCC
	TCATGGAAGATCCCTCGGGCTGGTGGAAGGGCCGGCTTCACGGCCAGGAGGGCCTTTTCCCAGGAAAC
	TACGTGGAGAACATCTGAGCTGGGCCCTCGGATACTGCCTTCTCTPTCGCCCGCCTATCTGCCTGCCG
	GCCTGGTGCGGAGCCAGGCCCTGCCAATGAGAGCCTCGTTTACCTGG
	ORF Start: ATG at 128	ORF Stop: TGA at 3416
	SEQ ID NO: 66	1096 aa	MW at 124743.0kD
NOV8a,	MGSKERFHWQSHNVKQSGVDDMVLLPQITEDAIAANLRKRFHDDYTFTYIGSVLISVNPFKQMPYPTD
CG125312-01
Protein	REIDLYQGAVQYENPPHIYALTDNMYRNMLIDCENQCVIISGESGAGKTVAAKYIMGYISKVSGGGEK
Sequence
	VQHVKDIILQSNPLLEAFGNAKTVRNNNSSRFGKYFEIQFSRGGEPDGGKISNFLLEKSRVVMQNENE
	RNFHIYYQLLEGASQEQRQNLGLMTPDYYYYLNQSDTYQVDGTDDRSDFGETLSAMQVIGIPPSIQQL
	VLQLVAGILHLGNISFCEDGNYARVESVDLAFPAYLLGIDSGRLQEKLTSRKNDSRWGGRSESINVTL
	NVEQAAYTRDALAKGLYARLFDFLVEAINRAMQKPQEEYSIGVLDIYGFEIFQKNGFEQFCINFVNEK
	LQQIFIELTLKAEQEEYVQEGIRWTPIQYFNNKVVCDLIENKLSPPGIMSVLDDVCATNHATGGGADQ
	TLLQKLQAAVGTHEHFNSWSAGFVIHHYAGKVSYDVSGFCERNRDVLFSDLIELMQTSEQFLRMLFPE
	KLDGDKKGRPSTAGSKIKKQANDLVATLNRCTPHYIRCIKPNETKRPRDWEENRVKHQVEYLGLKENI
	RVRRAGFAYRRQFAKFLQRYAILTPETWPRWRGDERQGVQHLLRAVNMEPDQYQMGSTKVFVKNPESL
	FLLEEVRERKFDGFARTIQKAWRRHVAVRKYEEMREEASNILLNKKERRRNSINRNFVGDYLGLEERP
	ELRQFLGKRERVDFADSVTKYDRRFKPIKRDLILTPKCVYVIGREKVKKGPEKGQVCEVLKKKVDTQA
	LRGVSLSTRQDDFFILQEDAADSFLESVFKTEFVSLLCKRFEEATRRPLPLTFSDRLQFRVKKEGWGG
	GGTRSVTFSRGFGDLAVLKVGGRTLTVSVGDGLPKSSEPTRKGMAXGKPRRSSQAPTRAAPAPPRGMD
	RNGVPPSARGGPLPLEIMSGGGTHRPPRGPPSTSLGASRRPRARPPSEUNTEFLNVPDQGMAGMQRKR
	SVGQRPVPGVGRPKPQPRTHGPRCRALYQYVGQDVDELSFNVNEVIEILMEDPSGWWKGRLHGQEGLF
	PGNYVEKI

[0393] Further analysis of the NOV8a protein yielded the following properties shown in Table 8B.

TABLE 8B
Protein Sequence Properties NOV8a
PSort analysis:   0.9800 probability located in nucleus; 0.4008
                  probability located in microbody (peroxisome);
                  0.1619 probability located in lysosome (lumen);
                  0.1000 probability located in mitochondrial
                  matrix space
SignalP analysis: No Known Signal Sequence Predicted

[0394] 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
Geneseq	Protein/Organism/Length	Match	for the	Expect
Identifier	[Patent #, Date]	Residues	Matched Region	Value
AAU97544	Human Myosin-1F protein	1 . . . 1096	1089/1098 (99%)	0.0
	MYO1F - Homo sapiens,	1 . . . 1098	1092/1098 (99%)
	1098 aa.
	[WO200218946-A2,
	07 MAR. 2002]
ABB97258	Novel human protein SEQ	63 . . . 1096	994/1097 (90%)	0.0
	ID NO: 526 - Homo sapiens,	1 . . . 1089	1006/1097 (91%)
	1089 aa.
	[WO200222660-A2,
	21 MAR. 2002]
AAM39991	Human polypeptide SEQ ID	18 . . . 718	327/724 (45%)	e−173
	NO 3136 - Homo sapiens,	47 . . . 761	453/724 (62%)
	1063 aa.
	[WO200153312-A1,
	26 JUL. 2001]
ABG10171	Novel human diagnostic	18 . . . 718	327/724 (45%)	e−173
	protein #10162 - Homo	33 . . . 747	453/724 (62%)
	sapiens, 1050 aa.
	[WO200175067-A2,
	11 OCT. 2001]
AAB64616	Human secreted protein	18 . . . 686	319/701 (45%)	e−169
	BLAST search protein SEQ	16 . . . 697	438/701 (61%)
	ID NO: 126 - Homo sapiens,
	697 aa. [WO200077197-A1,
	21 DEC. 2000]

[0395] 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
Accession		Match	for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
AAH28071	Hypothetical 124.8 kDa	1 . . . 1096	1093/1098 (99%)	0.0
	protein - Homo sapiens	1 . . . 1098	1094/1098 (99%)
	(Human), 1098 aa.
Q8WWN7	Myosin-1F - Homo sapiens	1 . . . 1096	1089/1098 (99%)	0.0
	(Human), 1098 aa.	1 . . . 1098	1092/1098 (99%)
BAC03995	CDNA FLJ35558 fis, clone	1 . . . 1087	1083/1089 (99%)	0.0
	SPLEN2004984, highly	1 . . . 1089	1084/1089 (99%)
	similar to M. musculus
	myosin I - Homo sapiens
	(Human), 1098 aa.
P70248	Myosin If - Mus musculus	1 . . . 1096	993/1107 (89%)	0.0
	(Mouse), 1099 aa.	1 . . . 1099	1042/1107 (93%)
Q90748	Brush border myosin IB -	1 . . . 1096	917/1102 (83%)	0.0
	Gallus gallus (Chicken),	1 . . . 1099	996/1102 (90%)
	1099 aa.

[0396] PFam analysis predicts that the NOV8a protein contains the domains shown in the Table 8E.

TABLE 8E
Domain Analysis of NOV8a
		Identities/
	NOV8a	Similarities
	Match	for the	Expect
Pfam Domain	Region	Matched Region	Value
myosin_head	19 . . . 675	336/736 (46%)	0
		549/736 (75%)
IQ	692 . . . 712	8/21 (38%)	0.96
		16/21 (76%)
SH3	1042 . . . 1096	28/58 (48%)	2.2e−20
		49/58 (84%)

Example 9

[0397] 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: 67	1364 bp
NOV9a,	AGATCTTAGTCGAAGCTTGTGTGGAATTATTCCGGGACTTAGCAGTATCTTCCTTCCCCGAATGAATC
CG134439-01
DNA Sequence	CATTTGTTTTGATTGATCTTGCTGGAGCATTTGCTCTTTGTATTACATATATGCTCATTGAAATTAAT
	AATTATTTTGCCGTAGACACTGCCTCTGCTATAGCTATTGCCTTGATGACATTTGGCACTATGTATCC
	CATGAGTGTGTACAGTGGGAAAGTCTTACTCCAGACAACACCACCCCATGTTATTGGTCAGTTGGACA
	AACTCATCAGAGAGGTATCTACCTTAGATGGAGTTTTAGAAGTCCGAAATGAACATTTTTCGACCCTA
	GGTTTTGGCTCATTGGCTGGATCAGTGCATGTAAGAATTCGACGAGATGCCAATGAACAAATGGTTCT
	TGCTCATGTGACCAACAGGCTGTACACTCTAGTGTCTACTCTAACTGTTCAAATTTTCAAGGATGACT
	GGATTAGGCCTGGCTTATTGTCTGGGCCTCTTGCAGCCAATGTCCTAAACTTTTCAGATCATCACGTA
	ATCCCAATGCCTCTTTTAAAGGGTACTGATGGTTTGAACCCGTATGTTCATTTCCTTTGGAAGATTAA
	TTTTTTCCTTTTTTTTGACATGGAGTCTCTCTCTGTCGCCCAGGCTGGAGTGCAGTGGCACGATCTTG
	GCTCACTGCAACCCCACCTCCCAGGTTCAAGCAATTCTGCCTGCCTCAGCCTCCCGAGTAGCTGCGAT
	TACAGGCATGCACCACCACACTTGCCTAATTTTTGTATTATTAGTAAAGATGGGGTTCTGCCATGTTG
	GCCATCCTGGTCTTGAACTCGTGACCTAAGGTGATCTGCCTGCCTTGGCCTCCCAAACTGCTGGGATT
	ACAGGTGTGAGCCACTACACCCGGCCTGATTAATTTCTTTTACTTGCTTCAAGTGTCTCCTTTATTCC
	AGCCTACACATACAGGTAAATATTCCTAGGAAACTTTCAGCAAGTTAAATCCTATTATAAAATCCCAG
	AGTCAGTTGTCTAATTPTTATTTTATTTTATTATTATTATTTTTTTTGAGACAGGGTCTTGCTTTGTC
	ACCCAGGCTGGAGTGCAGTGGCGTGAACACAGCTCACCACAGCCTTCACCTCCCAGGCTCAAGTGATC
	GTTCCAGTTCAGCCTCCTTAGTAGCTGGGATCACAGGTGCAGACCACCACACCCGACTAATTTTCTTT
	TTTTTTTTTTTAAGACAAGGTCTCACTCTGTCGTCCAGGCTGGAGTACAGTGAGCTGAGATTGTGCCA
	CTACTCCAGCCTGGGTGACAGAGCAAGACTCCATCTCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA
	AAAA
	ORF Start: ATG at 62	ORF Stop: TGA at 830
	SEQ ID NO: 68	256 aa	MW at 28494.7kD
NOV9a,	MNPFVLIDLAGAFALCITYMLIEINNYFAVDTASAIAIALMTFGTMYPMSVYSGKVLLQTTPPHVIGQ
CG134439-01
Protein	LDKLIREVSTLDGVLEVRNEHFWTLGFGSLAGSVHVRIRRDANEQMVLAHVTNRLYTLVSTLTVQIFK
Sequence
	DDWIRPGLLSGPVAANVLNFSDHHVIPMPLLKGTDGLNPYVHFLWXINFFLFFDMESLSVAQAGVQWH
	DLGSLQPHLPGSSNSACLSLPSSWDYRHAPPHLPNFCIISKDGVLPCWPCWS

[0398] Further analysis of the NOV9a protein yielded the following properties shown in Table 9B.

TABLE 9B
Protein Sequence Properties NOV9a
PSort analysis:   0.7762 probability located in outside; 0.2165
                  probability located in microbody (peroxisome);
                  0.1000 probability located in endoplasmic
                  reticulum (membrane); 0.1000 probability
                  located in endoplasmic reticulum (lumen)
SignalP analysis: Cleavage site between residues 54 and 55

[0399] 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
Geneseq	Protein/Organism/Length	Match	for the	Expect
Identifier	[Patent #, Date]	Residues	Matched Region	Value
ABG08221	Novel human diagnostic	26 . . . 175	148/150 (98%)	5e−81
	protein #8212 - Homo	239 . . . 388	148/150 (98%)
	sapiens, 477 aa.
	[WO200175067-A2,
	11 OCT. 2001]
AAM05878	Peptide #4560 encoded by	99 . . . 175	75/77 (97%)	4e−37
	probe for measuring breast	1 . . . 77	75/77 (97%)
	gene expression - Homo
	sapiens, 166 aa.
	[WO200157270-A2,
	09 AUG. 2001]
AAM02915	Peptide #1597 encoded by	99 . . . 175	75/77 (97%)	4e−37
	probe for measuring breast	1 . . . 77	75/77 (97%)
	gene expression - Homo
	sapiens, 166 aa.
	[WO200157270-A2,
	09 AUG. 2001]
AAM30756	Peptide #4793 encoded by	99 . . . 175	75/77 (97%)	4e−37
	probe for measuring placental	1 . . . 77	75/77 (97%)
	gene expression - Homo
	sapiens, 166 aa.
	[WO200157272-A2,
	09 AUG. 2001]
AAM27634	Peptide #1671 encoded by	99 . . . 175	75/77 (97%)	4e−37
	probe for measuring placental	1 . . . 77	75/77 (97%)
	gene expression - Homo
	sapiens, 166 aa.
	[WO200157272-A2,
	09 AUG. 2001]

[0400] 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
Q9NWI4	CDNA FLJ20837 fis, clone	49 . . . 256	207/208 (99%)	e−123
	ADKA02602 - Homo sapiens	1 . . . 208	207/208 (99%)
	(Human), 208 aa.
Q96NC3	CDNA FLJ31101 fis, clone	1 . . . 175	173/175 (98%)	2e−95
	IMR321000266, weakly	198 . . . 372	173/175 (98%)
	similar to zinc/cadmium
	resistance protein - Homo
	sapiens (Human), 461 aa.
AAM27917	Zinc transporter 6 - Mus	1 . . . 175	164/175 (93%)	4e−89
	musculus (Mouse), 460 aa.	198 . . . 372	165/175 (93%)
Q8R4Z2	Zinc transporter-like 3	1 . . . 175	161/175 (92%)	1e−87
	protein - Mus musculus	198 . . . 372	163/175 (93%)
	(Mouse), 460 aa.
AAH32525	Similar to hypothetical	49 . . . 175	125/127 (98%)	5e−67
	protein MGC11963 - Homo	1 . . . 127	125/127 (98%)
	sapiens (Human), 216 aa.

[0401] PFam analysis predicts that the NOV9a protein contains the domains shown in the Table 9E.

TABLE 9E
Domain Analysis of NOV9a
		Identities/
		Similarities
	NOV9a	for the Matched	Expect
Pfam Domain	Match Region	Region	Value
Cation_efflux	30 . . . 123	24/97 (25%)	6e−14
		74/97 (76%)

Example 10

[0402] 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: 69	3450 bp
NOV10a,	CGCCCCGCGGGACCCGGACGGCGACGACGGGGGAATGTCCCGCTGGATCCGGCAGCAGCTGCGTTTT
CG137109.01
DNA Sequence	GACCCACCACATCAGAGTGACACAAGAACCATCTACGTAGCCAACAGGTTTCCTCAGAATGGCCTTT
	ACACACCTCAGAAATTTATAGATAACACGATCATTTCATCTAAGTACACTGTGTGCAATTTTCTTCC
	AAAAAATTTATTTGAACAGTTCAGAAOAGTGGCAAACTTTTATTTTCTTATTATATTTTTGGTTCAG
	CTTATGATTGATACACCTACCAGTCCAGTTACCAGTGGACTTCCATTATTCTTTGTGATAACACTAA
	CTGCCATAAAGCAGGGATATGAAGATTGGTTACGGCATAACTCAGATAATGAACTAAATGGACCTCC
	TGTTTATGTTGTTCGAAGTGGTGGCCTTGTAAAAACTACATCAAAAAACATTCGGGTGGGTGATATT
	GTTCGAATAGCCAAACATGAAATTTTTCCTGCAGACTTGGTGCTTCTGTCCTCAGATCGACTGGATG
	GTTCCTGTCACGTTACAACTCCTAGTTTGCACCGACAAACTAACCTGAAGACACATGTGGCAGTTCC
	AGAAACAGCATTATTACAAACACTTGCCAATTTCGACACTCTAGTAGCTGTAATAGAATGCCAGCAA
	CCAGAAGCAGACTTATACAGATTCATGGGACGAATGATCATAACCCAACAAATGGAACAAATTGTAA
	GGCCTCTGGGGCCCGAGAGTCTCCTGCTTCGTCGACCCACATTAAAAAACACAAAAGAAATTTTTGG
	TTTGTACATATTTAAACATTTTAAATTAGGTGTTGCGGTATACACTGGAATGCAAACTAAGATGGCA
	TTAAATTACAACAGCAAATCACAGAAACGATCTGCACTAGAAAAGTCAATGAATACATTTTTGATAA
	TTTATCTAGTAATTCTTATATCTCAAGCTGTCATCAGCACTATCTTGAAGTATACATGGCAAGCTGA
	AGAAAAATGGGATGAACCTTCCTATAACCAAAAAACACAACATCAAAGAAATAOCAGTAAGGTAGAG
	TACCTGTTTACAGATAAAACTGGTACACTGACAGAAAATGAGATGCAGTTTCCCCAATGTTCAATTA
	ATGGCATGAAATACCAAGAAATTAATGGTAGACTTGTACCCGAACGACCAACACCAGACTCTTCAGA
	AGGAAACTTATCTTATCTTAGTACTTTATCCCATCTTAACAACTTATCCCATCTTACAACCAGTTCC
	TCTTTCAGAACCAGTCCTGAAAATGAAACTGAACTAGTAAAAGAACATGATCTCTTCTTTAAAGCAG
	TCAGTCTCTGTCACACTGTACAGATTAGCAATGTTCAAACTGACTGCACTGGTGATGGTCCCTGGCA
	ATCCAACCTGGCACCATCGCAGTTGGAGTACTATGCATCTTCACCAGATGAAAAGGCTCTAGTAGAA
	GCTGCTGCAAGGATTCGTATTGTGTTTATTCCCAATTCTCAAGAAACTATGGAGGTTAAAACTCTTG
	GAAAACTGGAACGGTACAAACTGCTTCATATTCTGGAATTTGATTCACATCGTAGCACAATGAGTGT
	AATTGTTCAGGCACCTTCAGGTGACAAGTTATTATTTGCTAAAGGACCTGAGTCATCAATTCTCCCT
	AAATGTATAGGTGCAGAAATAGAAAAAACCACAATTCATGTAGATGAATTTGCTTTGAAAGGGCTAA
	GAACTCTGTGTATAGCATATAGAAAATTTACATCAAAAGAGTATCAGCAAATACATAAACGCATATT
	TGAAGCCAGGACTGCCTTGCACCAGCGGGAAGAGAAATTCGCACCTGTTTTCCAGTTCATAGAGAAA
	GACCTGATATTACTTGGAGCCACAGCAGTAGAAGACAGACTACAAGATAAACTTCCACAAACTATTG
	AAGCATTGAGAATGGCTGGTATCAAAGTATGGGTACTTACTGGGGATAAACATGAAACAGCTGTTAG
	TGTGAGTTTATCATGTGGCCATTTTCATAGAACCATGAACATCCTTGAACTTATAAACCAGAAATCA
	GACAGCGAGTCTCCTGAACAATTGAGCCAGCTTGCCAGAAGAATTACAGAGGATCATGTGATTCAGC
	ATGGGCTGGTAGTGGATGGGACCAGCCTATCTCTTGCACTCAGGGAGCATCAAAAACTATTTATGGA
	ACTTTGCACAAATTCTTCAGCTGTATTATGCTGTCGTATGGCTCCACTCCAGAAAGCAAAAGTAATA
	AGACTAATAAAAATATCACCTGAGAAACCTATAACATTCGCTGTTGCTGATGCTCCTAATGACGTAA
	GCATGATACAAGAAGCCCATGTTGGCATAGGAATCATGGGTAAAGAAGGAAGACACGCTGCAAGAAA
	CAGTGACTATGCAATAGCCACATTTAAGTTCCTCTCCAAATTGCTTTTTGTTCATGGTCATTTTTAT
	TATATTAGAATAGCTACCCTTGTACAGTATTTTTTTTATAAGAATGTGTGCTTTATCACACCCCAGT
	TTTTATATCAGTTCTACTGTTTGTTTTCTCACCAAACATTGTATGACACCGTCTACCTGACTTTATA
	CAATATTTGTTTTACTTCCCTACCTATTCTCATATATACTCTTTTCGAACAGCATGTAGACCCTCAT
	GTGTTACAAAATAAGCCCACCCTTTATCGAGACATTAGTAAAAACCGCCTCTTAAGTATTAAAACAT
	TTCTTTATTGCACCATCCTGGGCTTCAGTCATCCCTTTATTTTCTTTTTTGGATCCTATTTACTAAT
	AGGGAAAGATACATCTCTGCTTCGAAATCGCCAGATGTTTGCAAACTCCACATTTGGCACTTTGGTC
	TTCACAGTCATGGTTATTACAGTCACAGTAAACATGGCTCTGGAAACTCATTTTTGGACTTGGATCA
	ACCATCTCGTTACCTGGGGATCTATTATATTTTATTTTGTATTTTCCTTGTTTTATGGAGCGATTCT
	CTGGCCATTTTTGGGCTCCCAGAATATGTATTTTGTGTTTATTCAGCTCCTGTCAAGTGGTTCTGCT
	TGGTTTGCCATAATCCTCATGGTTGTTACATGTCTATTTCTTGATATCATAAAGAAGGTCTTTGACC
	GACACCTCCACCCTACAAGTACTGAAAAGCCACAGCTTACTGAAACAAATGCAGGTATCAACTGCTT
	GGACTCCATGTGCTCTTTCCCCGAAGGAGAAGCAGCGTGTGCATCTGTTGGAAGAATGCTGGAACGA
	GTTATAGGAAGATCTAGTCCAACCCACATCACCAGATCATGGAGTGCATCGGATCCTTTCTATACCA
	ACGACAGGAGCATCTTGACTCTCTCCACAATGGACTCATCTACTTGTTAAAGGGGCAGTAGTACTTT
	GTGGCAGCCAGTTCACCTCCTTTCCTAAAATTC
	ORF Start: ATG at 35	ORF Stop: TAA at 3398
	SEQ ID NO: 70	1121 aa	MW at 127704.1kD
NOV10a,	MWRWIRQQLGFDPPHQSDTRTIYVANRFPQNGLYTPQKFIDNRIISSKYTVWNFVPKNLFEQFRRVA
CS137109-01
Protein Sequence	NFYFLIIFLVQLMIDTFTSPVTSGLPLFFVITVTAIKQGYEDWLRHNSDNEVNCAPVYVVRSGGLVK
	TRSKNIRVGDIVRIAKDEIFPADLVLLSSDRLDGSCHVTTASLDCETNLKTHVAVPETALLQTVANL
	DTLVAVIECQQFEADLYRFMGRMIITQQMEEIVRPLCPESLLLRGARLKNTKEIFCLYIFKHFKLGV
	AVYTCMETKMALNYKSKSQKRSAVEKSMNTFLIIYLVILISEAVISTILKYTWQAEEKWDEPWYNQK
	TEHQRNSSKVEYVFTDKTGTLTENEMQFRECSINGMXYQEINGRLVPEGPTPDSSEGNLSYLSSLSH
	LNNLSHLTTSSSFRTSPENETELVKEHDLFFKAVSLCHTVQISNVQTDCTGDGPWQSNLAFSQLEYY
	ASSPDEKALVEAAARIGIVFICNSEETMEVKTLGKLERYKLLHILEFDSDRRRMSVIVQAFSGEKLL
	FAKGAESSILPKCIGGEIEKTRIHVDEFALKCLRTLCIAYRKFTSKEYEEIDKRIFEARTALQQREE
	KLAAVFQFIEKDLILLCATAVEDRLQDKVRETIEALRMAGIKVWVLTGDKHETAVSVSLSCCHFHRT
	MNILELINQKSDSECAEQLRQLARRITEDHVIQNGLVVDCTSLSLALREHEKLFMEVCRNCSAVLCC
	RMAPLQKAKVIRLIKISPEKPITLAVGDCANDVSMIQEAHVGIGIMCKEGRQAARNSDYAIARFKFL
	SKLLFVHGHFYYIRTATLVQYFFYKNVCFITPQFLYQFYCLFSQQTLYDSVYLTLYNICFTSLPILI
	YSLLEQHVDPHVLQNKPTLYRDISKNRLLSIKTFLYWTILGFSHAFIFFFGSYLLIGKDTSLLGNGQ
	NFGNWTFGTLVFTVMVITVTVKMALETHFWTWINHLVTWCSIIFYFVFSLFYCCILWPFLGSQNMYF
	VFTQLLSSCSAWFAIILMVVTCLFLDIIKKVFDRULHFTSTEKAQLTETUAGIKCLDSMCCFPEGEA
	ACASVGRMLERVIGRCSPTHISRSWSASDPFYTNDRSTLTLSTMDSSTC

[0403] Further analysis of the NOV10a protein yielded the following properties shown in Table 10B.

TABLE 10B
Protein Sequence Properties NOV10a
PSort     0.6000 probability located in plasma membrane; 0.4000
analysis: probability located in Golgi body; 0.3000 probability
          located in endoplasmic reticulum (membrane); 0.3000
          probability located in microbody (peroxisome)
SignalP   No Known Signal Sequence Predicted
analysis:

[0404] 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
Geneseq	Protein/Organism/Length	Match	for the	Expect
Identifier	[Patent #, Date]	Residues	Matched Region	Value
AAO14203	Human transporter and ion	1 . . . 1095	1084/1095 (98%)	0.0
	channel TRICH-20 - Homo	1 . . . 1085	1085/1095 (98%)
	sapiens, 1096 aa.
	[WO200204520-A2,
	17 JAN. 2002]
AAG67546	Amino acid sequence of a	1 . . . 1121	1064/1187 (89%)	0.0
	human transporter protein -	1 . . . 1177	1081/1187 (90%)
	Homo sapiens, 1177 aa.
	[WO200164878-A2,
	07 SEP. 2001]
AAM39290	Human polypeptide SEQ ID	327 . . . 1121	780/804 (97%)	0.0
	NO 2435 - Homo sapiens,	12 . . . 815	789/804 (98%)
	815 aa. [WO200153312-A1,
	26 JUL. 2001]
AAM41076	Human polypeptide SEQ ID	344 . . . 1121	775/778 (99%)	0.0
	NO 6007 - Homo sapiens,	5 . . . 782	778/778 (99%)
	782 aa. [WO200153312-A1,
	26 JUL. 2001]
AAO14200	Human transporter and ion	18 . . . 1050	591/1129 (52%)	0.0
	channel TRICH-17 - Homo	22 . . . 1109	759/1129 (66%)
	sapiens, 1192 aa.
	[WO200204520-A2,
	17 JAN. 2002]

[0405] 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 10D.

TABLE 10D
Public BLASTP Results for NOV10a
		NOV10a	Identities/
Protein		Residues/	Similarities
Accession		Match	for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
Q9N0Z4	RING-finger binding	9 . . . 1121	1047/1117 (93%)	0.0
	protein - Oryctolagus	1 . . . 1107	1080/1117 (95%)
	cuniculus (Rabbit), 1107
	aa (fragment).
Q9Y2G3	Potential	450 . . . 1121	672/672 (100%)	0.0
	phospholipid-transporting	1 . . . 672	672/672 (100%)
	ATPase IR (EC 3.6.3.1) -
	Homo sapiens (Human), 672
	aa (fragment).
Q8R0F1	Hypothetical 69.8 kDa	508 . . . 1121	573/614 (93%)	0.0
	protein - Mus musculus	1 . . . 613	596/614 (96%)
	(Mouse), 613 aa (fragment).
T42662	hypothetical protein	698 . . . 1121	424/424 (100%)	0.0
	DKFZp434N1615.1 - human,	1 . . . 424	424/424 (100%)
	424 aa (fragment).
P98196	Potential	299 . . . 1050	407/789 (51%)	0.0
	phospholipid-transporting	15 . . . 772	537/789 (67%)
	ATPase IS (EC 3.6.3.1) -
	Homo sapiens (Human), 797
	aa (fragment).

[0406] PFam analysis predicts that the NOV10a protein contains the domains shown in the Table 10E.

[0407] PFam analysis predicts that the NOV10a protein contained the domains shown in the Table 10E.

TABLE 10E
Domain Analysis of NOV10a
		Identities/
		Similarities
	NOV10a	for the Matched	Expect
Pfam Domain	Match Region	Region	Value
E1-E2_ATPase	126 . . . 164	10/39 (26%)	0.13
		32/39 (82%)
Hydrolase	345 . . . 786	48/453 (11%)	6.6e−09
		277/453 (61%)

Example 11

[0408] 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: 71	2077 bp
NOV11a,	GGCGAGGCGAGGTTTGCTGGOGTGAGGCAGCGGCGCGGCCGGGCCGGGCCGOGCCACAGGCGGTGGC
CG137330-01
DNA Sequence	GGCGGGACCATGGACGCGGCGGTCGCTGCTCCGCGTCCCCGGCTGCTCCTCCTCGTGCTGGCGGCGG
	CGGCGGCGGCGGCGGCCGCGCTGCTCCCGGGGGCGACGGCGTTACAGTGTTTCTGCCACCTCTGTAC
	AAAAGACAATTTTACTTGTGTGACAGATGGGCTCTGCTTTGTCTCTGTCACAGAGACCACAGACAAA
	GTTATACACAACAGCATGTGTATAGCTGAAATTGACTTAATTCCTCGAGATAGGCCGTTTGTATGTG
	CACCCTCTTCAAAAACTGGGTCTGTGACTACAACATATTCCTGCAATCAGGACCATTGCAATAAAAT
	AGAACTTCCAACTACTGGTTTACCATTGCTTGTTCAGAGAACAATTGCGAGAACTATTGTGTTACAA
	GAAAGCATTGGCAAAGGTCGATTTGGAGAAGTTTGGAGAGGAAAGTCGCGGGGAGAAGAAGTTGCTG
	TTAAGATATTCTCCTCTACAGAAGAACGTTCGTGGTTCCGTGAGGCAGAGATTTATCAAACTGTAAT
	GTTACGTCATGAAAACATCCTGGGATTTATAGCAGCAGACAATAAAGACAATGGTACTTGGACTCAG
	CTCTGGTTGGTGTCAGATTATCATGAGCATGGATCCCTTTTTGATTACTTAAACAGATACACAGTTA
	CTGTGGAAGGAATGATAAAACTTGCTCTGTCCACGGCCAGCGGTCTTGCCCATCTTCACATGGAGAT
	TGTTGGTACCCAAGGAAAGCCAGCCATTGCTCATAGAGATTTGAAATCAAAGAATATCTTGGTAAAG
	AAGAATGGAACTTGCTGTATTGCAGACTTAGGACTGGCAGTAAGACATGATTCAGCCACAGATACCA
	TTGATATTGCTCCAAACCACAGAGTGGGAACAAAAAGGTACATGGCCCCTGAAGTTCTCGATGATTC
	CATAAATATGAAACATTTTGAATCCTTCAAACGTGCTGACATCTATGCAATGGGCTTAGTATTCTGG
	GAAATTGCTCGACGATGTTCCATTGGTGGAATTCATGAAGATTACCAACTGCCTTATTATGATCTTG
	TACCTTCTGACCCATCAGTTGAAGAAATGAGAAAAGTTGTTTGTGAACAGAAGTTAAGGCCAAATAT
	CCCAAACAGATGGCAGAGCTGTGAAGCCTTGAGAGTAATGGCTAAAATTATGAGAGAATGTTGGTAT
	GCCAATGGAGCAGCTAGGCTTACAGCATTGCGGATTAAGAAAACATTATCGCAACTCAGTCAACAGG
	AAGGCATCAAAATGTAATTCTACAGCTTTGCCTGAACTCTCCTTTTTTCTTCAGATCTGCTCCTGGG
	TTTTAATTTGGGAGGTCAGTTGTTCTACCTCACTGAGAGGGAACAGAAGGATATTGCTTCCTTTTGC
	AGCAGTGTAATAAAGTCAATTAAAAACTTCCCAGGATTTCTTTGGACCCAGGAAACAGCCATGTGGG
	TCCTTTCTGTGCACTATGAACGCTTCTTTCCCAGGACAGAAAATGTGTAGTCTACCTTTATTTTTTA
	TTAACAAAACTTGTTTTTTAAAAAGATGATTGCTGGTCTTAACTTTAGGTAACTCTGCTGTGCTGGA
	GATCATCTTTAAGGGCAAAGGAGTTGGATTCCTGAATTACAATGAAACATGTCTTATTACTAAAGAA
	AGTGATTTACTCCTGGTTAGTACATTCTCAGAGGATTCTGAACCACTAGAGTTTCCTTGATTCAGAC
	TTTGAATGTACTGTTCTATAGTTTTTCAGGATCTTAAAACTAACACTTATAAAACTCTTATCTTGAG
	TCTAAAAATCACCTCATATAGTAGTGAGGAACATAATTCATGCAATTGTATTTTGTATACTATTATT
	GTTCTTTCACTTATTCAGAACATTACATGCCTTCAAAATGGGATTGTACTATACCAGTAAGTGCCAC
	TTCTGTGTCTTTCTAATGGAAATGAGTAGAATTGCTGAAAGTCTCTATGTTAAAACCTATAGTGTTT
	ORF Start: ATG at 77	ORF Stop: TAA at 1355
	SEQ ID NO: 72	426 aa	MW at 47689.6kD
NOV11a,	MEAAVAAPRPRLLLLVLAAAAAAAAALLPGATALQCFCHLCTKDNFTCVTDGLCFVSVTETTDKVIH
CG137330-01
Protein Sequence	NSMCIAEIDLIPRDRPFVCAPSSKTGSVTTTYCCNQDHCNKIELPTTGLPLLVQRTIARTIVLQESI
	GKGRFGEVWRGKWRGEEVAVKIFSSREERSWFREAEIYQTVMLRHENILGFIAADNKDNGTWTQLWL
	VSDYHEHGSLFDYLNRYTVTVEGMIKLALSTASGLAHLHNEIVGTQGKPAIARRDLKSKNILVKKNG
	TCCIADLGLAVRHDSATDTIDIAPNHRVGTKRYMAPEVLDDSINMKHFESFKRADIYAMGLVFWEIA
	RRCSIGGIHEDYQLPYYDLVPSDPSVEEMRKVVCEQKLRPNIPNRWQSCEALRVMAKIMRECWYANG
	AARLTALRIKKTLSQLSQQEGIKM

[0409] Further analysis of the NOV11a protein yielded the following properties shown in Table 11B.

TABLE 11B
Protein Sequence Properties NOV11a
PSort     0.8200 probability located in outside; 0.1900
analysis: probability located in lysosome (lumen); 0.1038
          probability located in microbody (peroxisome); 0.1000
          probability located in endoplasmic reticulum (membrane)
SignalP   Cleavage site between residues 34 and 35
analysis:

[0410] 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
Geneseq	Protein/Organism/Length	Match	for the	Expect
Identifier	[Patent #, Date]	Residues	Matched Region	Value
AAY59452	Human Transforming growth	114 . . . 426	312/313 (99%)	0.0
	factor-beta protein sequence -	191 . . . 503	313/313 (99%)
	Homo sapiens, 503 aa.
	[JP11326328-A,
	26 NOV. 1999]
AAY33303	Human hALK-5 clone	114 . . . 426	312/313 (99%)	0.0
	EMBLA protein - Homo	191 . . . 503	313/313 (99%)
	sapiens, 503 aa.
	[WO9946386-A1,
	16 SEP. 1999]
AAW03758	Mullerian inhibiting	114 . . . 426	312/313 (99%)	0.0
	substance receptor MISR4 -	189 . . . 501	313/313 (99%)
	Rattus sp, 501 aa.
	[US5538892-A,
	23 JUL. 1996]
AAR70241	Serine/threonine kinase	114 . . . 426	312/313 (99%)	0.0
	receptor W120 - Mus	191 . . . 503	313/313 (99%)
	musculus, 503 aa.
	[WO9507982-A,
	23 MAR. 1995]
AAR41923	MISR4 - Rattus rattus, 501	114 . . . 426	312/313 (99%)	0.0
	aa. [WO9319177-A,	189 . . . 501	313/313 (99%)
	30 SEP. 1993]

[0411] 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
		NOV11a	Identities/
Protein		Residues/	Similarities
Accession		Match	for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
JC2062	transforming growth factor	114 . . . 426	312/313 (99%)	0.0
	beta receptor type I	187 . . . 499	313/313 (99%)
	precursor - mouse, 499 aa.
Q9D5H8	Transforming growth factor,	114 . . . 426	312/313 (99%)	0.0
	beta receptor I - Mus	108 . . . 420	313/313 (99%)
	musculus (Mouse), 420 aa.
P80204	TGF-beta receptor type I	114 . . . 426	312/313 (99%)	0.0
	precursor (EC 2.7.1.37)	189 . . . 501	313/313 (99%)
	(TGFR-1) (TGF-beta type I
	receptor)
	(Serine/threonine-protein
	kinase receptor R4) (SKR4) -
	Rattus norvegicus (Rat), 501
	aa.
Q64729	TGF-beta receptor type I	114 . . . 426	312/313 (99%)	0.0
	precursor (EC 2.7.1.37)	191 . . . 503	313/313 (99%)
	(TGFR-1) (TGF-beta type I
	receptor) (ESK2) - Mus
	musculus (Mouse), 503 aa.
P36897	TGF-beta receptor type I	114 . . . 426	312/313 (99%)	0.0
	precursor (EC 2.7.1.37)	191 . . . 503	313/313 (99%)
	(TGFR-1) (TGF-beta type I
	receptor)
	(Serine/threonine-protein
	kinase receptor R4) (SKR4)
	(Activin receptor-like kinase
	5) (ALK-5) - Homo sapiens
	(Human), 503 aa.

[0412] PFam analysis predicts that the NOV11a protein contains the domains shown in the Table 11E.

TABLE 11E
Domain Analysis of NOV11a
		Identities/
		Similarities
	NOV11a	for the Matched	Expect
Pfam Domain	Match Region	Region	Value
Activin_recp	21 . . . 114	40/118 (34%)	9.4e−30
		77/118 (65%)
pkinase	128 . . . 415	85/312 (27%)	6.1e−61
		222/312 (71%)

Example 12

[0413] 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: 73	5367 bp
NOV12a,	GCCGCGCTGCGCCGGAGTCCCGAGCTAGCCCCGGCGCCGCCGCCGCCCAGACCGGACGACAGGCCAC
CS137339-01
DNA Sequence	CTCGTCGGCGTCCGCCCGAGTCCCCGCCTCGCCGCCAACGCCACAACCACCCCGCACGGCCCCCTGA
	CTCCGTCCAGTATTGATCGGGAGAGCCGGAGCGAGCTCTTCGGGGAGCAGCGATGCGACCCTCCGGG
	ACGGCCCGGGCAGCGCTCCTGGCGCTGCTGGCTGCGCTCTGCCCGGCGAGTCGGGCTCTGGAGGAAA
	AGAAAGTTTGCCAAGGCACGAGTAACAAGCTCACOCAGTTCGGCACTTTTGAAGATCATTTTCTCAG
	CCTCCACACGATGTTCAATAACTGTGAGGTGGTCCTTGGGAATTTGGAAATTACCTATGTGCAGAGG
	AATTATGATCTTTCCTTCTTAAAGACCATCCAGGAGGTGGCTGGTTATGTCCTCATTGCCCTCAACA
	CAGTGGAGCCAATTCCTTTGGAAAACCTGCAGATCATCAGAGGAAATATGTACTACGAAAATTCCTA
	TGCCTTAGCAGTCTTATCTAACTATGATGCAAATAAAACCGGACTGAAGGAGCTGCCCATGAGAAAT
	TTACAGGAAATCCTGCATGGCGCCGTGCGGTTCAGCAACAACCCTGCCCTGTGCAACGTGGAGAGCA
	TCCAGTGGCGGGACATAGTCAGCAGTGACTTTCTCAGCAACATGTCGATGGACTTCCAGAACCACCT
	GGGCAGCTGCCAAAAGTGTGATCCAAGCTGTCCCAATGGGACCTGCTGGGGTGCAGGAGAGCAGAAC
	TGCCAGAAACTGACCAAAATCATCTGTGCCCAGCAGTGCTCCGGGCGCTGCCGTGGCAAGTCCCCCA
	GTGACTGCTGCCACAACCAGTGTGCTGCAGGCTGCACAGGCCCCCGGGAGAGCGACTGCCTGGTCTG
	CCGCAAATTCCGAGACGAAGCCACGTGCAAGGACACCTGCCCCCCACTCATGCTCTACAACCCCACC
	ACGTACCAGATGGATGTGAACCCCGAGGGCAAATACAGCTTTGGTGCCACCTGCCTGAAGAAGTGTC
	CCCGTAATTATGTGGTGACAGATCACGGCTCGTGCGTCCGAGCCTGTGGGGCCGACAGCTATGAGAT
	GGAGGAAGACGGCGTCCGCAAGTGTAAGAACTGCGAAGGGCCTTGCCGCAAAGTGTGTAACGGAATA
	GGTATTGGTGAATTTAAAGACTCACTCTCCATAAATGCTACGAATATTAAACACTTCAAAAACTGCA
	CCTCCATCAGTGGCGATCTCCACATCCTGCCGGTGGCATTTAGGGGTGCTCAGTTTTCTCTTGCAGT
	CGTCAGCCTGAACATAACATCCTTGGGATTACGCTCCCTCAAGGAGATAAGTGATGGAGATGTGATA
	ATTTCAGGAAACAAAAATTTGTGCTATGCAAATACAATAAACTGGAAAAAACTGTTTGGGACCTCCG
	GTCAGAAAACCAAAATTATAAGCAACAGAGGTGAAAACAGCTGCAAGGCCACAGGCCAGGTCTGCCA
	TGCCTTGTGCTCCCCCGAGGGCTGCTGGGGCCCGGAGCCCAGGGACTGCGTCTCTTGCCGGAATGTC
	AGCCGACGCAGGGAATGCGTGGACAAGTGCAACCTTCTGGAGGGGGAGCCAAGGGAGTTTGTGGAGA
	ACTCTGAGTGCATACAGTGCCACCCAGAGTGCCTGCCTCAGGCCATGAACATCACCTGCACAGGACG
	GGGACCAGACAACTGTATCCAGTGTGCCCACTACATTGACGGCCCCCACTGCGTCAAGACCTGCCCG
	GCAGGAGTCATGGGAGAAAACAACACCCTGGTCTGGAAGTACGCAGACGCCGGCCATGTGTGCCACC
	TGTGCCATCCAAACTGCACCTACGGATGCACTGGGCCAGGTCTTGAAGGCTGTCCAACGAATGGGCC
	TAAGATCCCGTCCATCGCCACTGGGATGGTGGGGGCCCTCCTCTTGCTGCTGGTCGTGGCCCTGGGG
	ATCGGCCTCTTCATGCGAAGGCGCCACATCGTTCGGAAGCGCACGCTGCGGAGGCTGCTGCAGGAGA
	GGGAGCTTGTGGAGCCTCTTACACCCAGTGGAGAAGCTCCCAACCAAGCTCTCTTGAGGATCTTGAA
	GGAAACTGAATTCAAAAAGATCAAAGTGCTGGGCTCCGGTGCGTTCGGCACGGTGTATAAGGGACTC
	TGGATCCCAGAAGGTGAGAAAGTTAAAATTCCCGTCGCTATCAAGGAATTAAGAGAAGCAACATCTC
	CGAAAGCCAACAAGGAAATCCTCGATGAAGCCTACGTGATCGCCAGCGTGGACAACCCCCACGTGTG
	CCGCCTGCTGGGCATCTGCCTCACCTCCACCGTGCAACTCATCACGCAGCTCATGCCCTTCCGCTGC
	CTCCTGGACTATGTCCGGGAACACAAAGACAATATTGGCTCCCAGTACCTGCTCAACTGGTGTGTGC
	AGATCGCAAAGGGCATGAACTACTTCGAGGACCGTCGCTTGGTGCACCGCGACCTGGCAGCCAGGAA
	CGTACTGGTGAAAACACCGCAGCATGTCAAGATCACAGATTTTGGGCTGGCCAAACTGCTGGGTGCG
	GAAGAGAAAGAATACCATGCAGAAGGAGGCAAAGTGCCTATCAAGTGGATGGCATTGGAATCAATTT
	TACACAGAATCTATACCCACCAGAGTGATGTCTGGAGCTACGGGGTGACCGTTTGGGAGTTGATGAC
	CTTTGGATCCAAGCCATATGACGGAATCCCTGCCAGCGAGATCTCCTCCATCCTGGAGAAAGGAGAA
	CGCCTCCCTCAGCCACCCATATGTACCATCGATGTCTACATGATCATGGTCAAGTGCTGGATGATAG
	ACGCAGATAGTCGCCCAAAGTTCCGTGAGTTGATCATCGAATTCTCCAAAATGGCCCGAGACCCCCA
	GCGCTACCTTGTCATTCAGGGGGATGAAAGAATGCATTTGCCAAGTCCTACAGACTCCAACTTCTAC
	CGTGCCCTGATGGATGAAGAAGACATGGACGACGTGGTGGATGCCGACGAGTACCTCATCCCACAGC
	AGGGCTTCTTCAGCAGCCCCTCCACGTCACGGACTCCCCTCCTGAGCTCTCTGAGTGCAACCAGCAA
	CAATTCCACCGTGGCTTGCATTGATAGAAATGGGCTGCAAAGCTGTCCCATCAAGGAAGACAGCTTC
	TTGCAGCGATACAGCTCAGACCCCACAGGCGCCTTGACTGAGGACAGCATAGACGACACCTTCCTCC
	CAGTGCCTGAATACATAAACCAGTCCGTTCCCAAAAGGCCCGCTGGCTCTGTGCAGAATCCTGTCTA
	TCACAATCAGCCTCTGAACCCCGCGCCCAGCAGAGACCCACACTACCAGGACCCCCACAGCACTGCA
	GTGGGCAACCCCGAGTATCTCAACACTGTCCAGCCCACCTGTGTCAACAGCACATTCGACAGCCCTG
	CCCACTGGGCCCAGAAAGGCAGCCACCAAATTAGCCTCGACAACCCTGACTACCAGCAGGACTTCTT
	TCCCAAGGAACCCAAGCCAAATCGCATCTTTAAGGGCTCCACAGCTGAAAATGCAGAATACCTAAGG
	GTCGCGCCACAAAGCAGTGAATTTATTGGAGCATGACCACGGAGGATAGTATGAGCCCTAAAAATCC
	AGACTCTTTCGATACCCAGGACCAAGCCACAGCAGGTCCTCCATCCCAACAGCCATGCCCGCATTAG
	CTCTTAGACCCACAGACTGGTTTTGCAACGTTTACACCGACTAGCCAGGAAGTACTTCCACCTCGGG
	CACATTTTGGGAAGTTGCATTCCTTTGTCTTCAAACTGTGAAGCATTTACAGAAACCCATCCAGCAA
	GAATATTGTCCCTTTGAGCAGAAATTTATCTTTCAAAGAGGTATATTTCAAAAAAAAAAAAAAAGTA
	TATGTGAGGATTTTTATTGATTGGGGATCTTGGAGTTTTTCATTGTCGCTATTGATTTTTACTTCAA
	TGGGCTCTTCCAACAAGGAAGAAGCTTGCTCGTAGCACTTGCTACCCTGAGTTCATCCAGGCCCAAC
	TGTGAGCAAGGAGCACAAGCCACAAGTCTTCCAGAGGATGCTTGATTCCAGTGGTTCTGCTTCAAGG
	CTTCCACTGCAAAACACTAAAGATCCAAGAAGGCCTTCATGGCCCCAGCAGGCCGGATCGGTACTGT
	ATCAAGTCATGCCAGGTACAGTAGGATAAGCCACTCTGTCCCTTCCTGGGCAAAGAAGAAACGGAGG
	GGATGAATTCTTCCTTAGACTTACTTTTGTAAAAATGTCCCCACGGTACTTACTCCCCACTGATGGA
	CCAGTGGTTTCCAGTCATGAGCGTTAGACTGACTTGTTTGTCTTCCATTCCATTGTTTTGAAACTCA
	GTATGCCGCCCCTGTCTTGCTGTCATGAAATCAGCAAGAGAGGATGACACATCAAATAATAACTCGG
	ATTCCAGCCCACATTGGATTCATCAGCATTTGGACCAATAGCCCACAGCTGAGAATGTGGAATACCT
	AAGGATAACACCGCTTTTGTTCTCGCAAAAACGTATCTCCTAATTTGAGGCTCAGATGAAATGCATC
	AGGTCCTTTGGGGCATAGATCAGAAGACTACAAAAATCAACCTGCTCTGAAATCTCCTTTAGCCATC
	ACCCCAACCCCCCAAAATTAGTTTGTGTTACTTATGGAAGATAGTTTTCTCCTTTTACTTCACTTCA
	AAAGCTTTTTACTCAAAGAGTATATGTTCCCTCCAGGTCAGCTGCCCCCAAACCCCCTCCTTACGCT
	TTGTCACACAAAAAGTGTCTCTGCCTTGAGTCATCTATTCAAGCACTTACAGCTCTGGCCACAACAG
	GGCATTTTACAGGTGCGAATGACAGTAGCATTATGAGTAGTGTGAATTCAGGTAGTAAATATGAAAC
	TAGGGTTTGAAATTGATAATGCTTTCACAACATTTGCAGATGTTTTAGAAGGAAAAAAGTTCCTTCC
	TAAAATAATTTCTCTACAATTGGAAGATTGGAAGATTCAGCTAGTTAGGAGCCCATTTTTTCCTAAT
	CTGTGTGTGCCCTGTAACCTGACTGGTTAACAGCAGTCCTTTGTAAACAGTGTTTTAAACTCTCCTA
	GTCAATATCCACCCCATCCAATTTATCAAGGAACAAATGGTTCAGAAAATATTTTCAGCCTACAGTT
	ATGTTCAGTCACACACACATACAAAATGTTCCTTTTGCTTTTAAAGTAATTTTTGACTCCCAGATCA
	GTCAGAGCCCCTACAGCATTGTTAAGAAAGTATTTGATTTTTGTCTCAATGAAAATAAAACTATATT
	CATTTCC
	ORF Start: ATG at 187	ORF Stop: TGA at 3652
	SEQ ID NO: 74	1155 aa	MW at 127869.7kD
NOV12a,	MRPSGTAGAALLALLAALCPASRALEEKKVCQGTSNKLTQLGTPEDHFLSLQRMFNNCEVVLGNLEI
CG137339-01
Protein Sequence	TYVQRNYDLSFLKTIQEVAGYVLIALNTVERIPLENLQIIRGNMYYENSYALAVLSNYDANXTGLKE
	LPMRNLQEILHGAVRFSNNPALCNVESIQWRDIVSSDFLSNMSMDFQNHLGSCQKCDPSCPNGSCWG
	AGEENCQKLTKIICAQQCSGRCRGKSPSDCCHNQCAAGCTGPRESDCLVCRKFRDEATCKDTCPPLM
	LYNPTTYQMDVNPEGKYSEGATCVKKCPRNYVVTDHCSCVRACGADSYEMEEDGVRKCKKCEGPCRK
	VCNGTGIGEFKDSLSINATNIKHFKNCTSISGDLHILPVAFRGGQFSLAVVSLNITSLGLRSLKEIS
	DGDVIISGNXNLCYANTINWKKLFGTSGQKTKIISNRGENSCKATGQVCHALCSPEGCWGPEPRDCV
	SCRNVSRGRECVDKCNLLEGEPREFVENSECIQCHPECLPQAMNTTCTGRGPDNCIQCAHYIDGPHC
	VKTCPAGVMGENNTLVWKYADAGHVCHLCHPNCTYGCTGPGLEGCPTNGPKIPSIATGNVGALLLLL
	VVALGIGLFMRRRHIVRKRTLRRLLQERELVEPLTPSGEAPNQALLRILKETEFKKIKVLGSGAFGT
	VYKGLWIPEGEKVKIPVAIKELREATSPKANKEILDEAYVMASVDNPHVCRLLGICLTSTVQLITQL
	NPFGCLLDYVREHKDNIGSQYLLNWCVQIAKGNNYLEDRRLVHRDLAARNVLVKTPQHVKITDFGLA
	KLLGAEEKEYHAEGGKVPIKWMALESILHRIYThQSDVWSYGVTVWELMTFGSKPYDGIPASEISSI
	LEKGERLPQPPICTIDVYMIMVKCWMIDADSRPKFRELIIEFSKMARDPQRYLVXQGDERMHLPSPT
	DSNFYRALMDEEDMDDVVDADEYLIPQQGFFSSPSTSRTPLLSSLSATSNNSTVACIDRNGLQSCPI
	KEDSFLQRYSSDPTGALTEDSIDDTFLPVPEYINQSVPKRPAGSVQNPVYHNQPLNPAPSRDPHYQD
	PHSTAVGNPEYLNTVQPTCVNSTFDSPAHWAQKGSHQISLDNPDYQQDFFPKEAKPNGIFKGSTAEN
	AEYLRVAPQSSEFIGA
	SEQ ID NO: 75	3633 bp
NOV12b,	ATGCGACCCTCCGGGACGGCCGGGGCAGCGCTCCTGGCGCTGCTGGCTGCGCTCTGCCCGGCGAGTC
CG137339-02
DNA Sequence	GGGCTCTGGAGGAAAAGAAAGTTTGCCAAGGCACGAGTAACAAGCTCACGCACTTGGGCACTTTTGA
	AGATCATTTTCTCAGCCTCCAOAGGATGTTCAATAACTGTGAGGTGGTCCTTGGGAATTTGGAAATT
	ACCTATGTGCAGAGGAATTATGATCTTTCCTTCTTAAAGACCATCCAGGAGGTGGCTGGTTATGTCC
	TCATTGCCCTCAACACAGTGGAGCGAATTCCTTTGGAAAACCTGCAGATCATCAGAGGAAATATGTA
	CTACGAAAATTCCTATGCCTTAGCAGTCTTATCTAACTATGATGCAAATAAAACCGGACTGAACGAG
	CTGCCCATGAGAAATTTACAGGAAATCCTGCATGGCGCCGTGCGGTTCAGCAACAACCCTGCCCTGT
	GCAACGTGGAGAGCATCCAGTGGCGGGACATAGTCAGCAGTGACTTTCTCAGCAACATGTCGATCGA
	CTTCCAGAACCACCTGGGCAGCTGCCAAAAGTGTGATCCAAGCTGTCCCAATGGGAGCTGCTGGCGT
	GCAGGAGAGGAGAACTGCCAGAAACTGACCAAAATCATCTGTGCCCAGCAGTGCTCCGGGCGCTGCC
	GTGGCAAGTCCCCCAGTGACTGCTGCCACAACCAGTGTGCTGCAGGCTGCACAGGCCCCCGGGAGAG
	CGACTGCCTGGTCTGCCGCAAATTCCGAGACGAAGCCACGTGCAAGGACACCTGCCCCCCACTCATG
	CTCTACAACCCCACCACGTACCAGATGGATGTGAACCCCGAGGGCAAATACAGCTTTGGTGCCACCT
	GCGTGAAGAAGTGTCCCCGTAATTATGTGOTGACAGATCACGGCTCGTGCGTCCGAGCCTGTGGGGC
	CGACAGCTATGAGATGGAGGAAGACGGCGTCCGCAAGTGTAAGAAGTGCGAAGGGCCTTGCCGCAAA
	GTGTGTAACGGAATAGGTATTGGTGAATTTAAAGACTCACTCTCCATAAATGCTACGAATATTAAAC
	ACTTCAAAAACTGCACCTCCATCAGTGGCGATCTCCACATCCTGCCGGTGGCATTTAGGGGTGACTC
	CTTCACACATACTCCTCCTCTGGATCCACAGGAACTGGATATTCTGAAAACCGTAAAGGAAATCACA
	GGGTTTTTGCTGATTCAGGCTTGGCCTGAAAACAGGACGGACCTCCATGCCTTTGAGAACCTAGAAA
	TCATACGCGGCAGGACCAAGCAACATGGTCAGTTTPCTCTTGCAGTCGTCAGCCTGAACATAACATC
	CTTGGGATTACGCTCCCTCAAGGAGATAAGTGATGGAGATGTGATAATTTCAGGAAACAAAAATTTG
	TGCTATGCAAATACAATAAACTGGAAAAAACTGTTTGGGACCTCCGGTCAGAAAACCAAAATTATAA
	GCAACAGAGGTGAAAACAGCTGCAAGGCCACAGGCCAGGTCTGCCATGCCTTGTGCTCCCCCGAGGG
	CTGCTGGGGCCCOGAGCCCAGGGACTGCGTCTCTTGCCGGAATGTCAGCCGAGGCAGGGAATGCGTG
	GACAAGTGCAAGCTTCTGGAGGGTGAGCCAAGGGAGTTTGTGGAGAACTCTGAGTGCATACAGTGCC
	ACCCAGAGTGCCTGCCTCAGGCCATGAACATCACCTGCACAGGACGGGGACCAGACAACTGTATCCA
	GTGTGCCCACTACATTGACGGCCCCCACTGCGTCAAGACCTGCCCGGCAGGAGTCATGGGAGAAAAC
	AACACCCTGGTCTGGAAGTACGCAGACGCCGGCCATGTGTGCCACCTGTGCCATCCAAACTGCACCT
	ACGGATGCACTGGGCCAGGTCTTGAAGGCTGTCCAACGAATGGGCCTAAGATCCCGTCCATCGCCAC
	TGGGATGGTGGGGGCCCTCCTCTTGCTGCTGGTGGTGGCCCTGGGGATCGGCCTCTTCATGCGAAGG
	CGCCACATCGTTCGGAAGCGCACGCTGCGGAGGCTGCTGCAGGAGAGGGAGCTTGTGGAGCCTCTTA
	CACCCAGTGGAGAAGCTCCCAACCAAGCTCTCTTGAGGATCTTGAAGGAAACTGAATTCAAAAAGAT
	CAAAGTGCTCGGCTCCGGTGCGTTCGGCACGGTGTATAAGGGACTCTGGATCCCAGAAGGTGAGAAA
	GTTAAAATTCCCGTCGCTATCAAGGAATTAAGAGAAGCAACATCTCCGAAAGCCAACAAGGAAATCC
	TCGATGAAGCCTACGTGATGGCCAGCGTGGACAACCCCCACGTGTGCCGCCTGCTGGGCATCTGCCT
	CACCTCCACCGTGCAACTCATCACGCAGCTCATGCCCTTCGGCTGCCTCCTGGACTATGTCCGGGAA
	CACAAAGACAATATTGGCTCCCAGTACCTGCTCAACTGGTGTGTGCAGATCGCAAAGGGCATGAACT
	ACTTGGAGGACCGTCGCTTGGTGCACCGCGACCTGGCAGCCAGGAACGTACTGGTGAAAACACCGCA
	GCATGTCAAGATCACAGATTTTGGGCTGGCCAAACTCCTGGGTGCGGAAGAGAAAGAATACCATGCA
	GAAGGAGGCAAAGTGCCTATCAAGTGGATGGCATTGGAATCAATTTTACACAGAATCTATACCCACC
	AGAGTGATGTCTGGAGCTACGGGGTGACCGTTTCGGAGTTGATGACCTTTGGATCCAAGCCATATGA
	CGGAATCCCTGCCAGCGAGATCTCCTCCATCCTGGAGAAAGGAGAACGCCTCCCTCAGCCACCCATA
	TGTACCATCCATGTCTACATGATCATGGTCAAGTGCTGGATGATAGACGCAGATAGTCGCCCAAAGT
	TCCGTGAGTTGATCATCGAATTCTCCAAAATGGCCCGAGACCCCCAGCGCTACCTTGTCATTCAGGG
	GGATGAAAGAATGCATTTGCCAAGTCCTACAGACTCCAACTTCTACCGTGCCCTGATGGATGAAGAA
	GACATGGACGACGTGGTGGATGCCGACGAGTACCTCATCCCACAGCAGGGCTTCTTCAGCAGCCCCT
	CCACGTCACGGACTCCCCTCCTGAGCTCTCTGAGTGCAACCAGCAACAATTCCACCGTGGCTTGCAT
	TGATAGAAATGGGCTGCAAAGCTGTCCCATCAAGGAAGACAGCTTCTTGCAGCGATACAGCTCAGAC
	CCCACAGGCGCCTTGACTGAGGACAGCATAGACGACACCTTCCTCCCAGTGCCTGAATACATAAACC
	AGTCCGTTCCCAAAAGGCCCGCTGGCTCTGTGCAGAATCCTGTCTATCACAATCAGCCTCTGAACCC
	CGCGCCCAGCAGAGACCCACACTACCAGGACCCCCACAGCACTGCAGTGGGCAACCCCGAGTATCTC
	AACACTGTCCAGCCCACCTGTGTCAACAGCACATTCGACAGCCCTGCCCACTGGGCCCAGAAAGGCA
	GCCACCAAATTAGCCTGGACAACCCTGACTACCAGCAGGACTTCTTTCCCAAGGAAGCCAAGCCAAA
	TGGCATCTTTAAGGCCTCCACAGCTGAAAATGCAGAATACCTAAGGGTCGCGCCACAAAGCAGTGAA
	TTTATTGGAGCATGA
	ORF Start: ATG at 1	ORF Stop: TGA at 3631
	SEQ ID NO: 76	1210 aa	MW at 134289.9kD
NOV12b,	MRPSGTAGAALLALLAALCPASRALEEKKVCQGTSNKLTQLGTFEDHFLSLQRMFNNCEVVLGNLEI
CG137339-02
Protein Sequence	TYVQRNYDLSFLKTIQEVAGYVLIALNTVERIPLENLQIIRGNMYYENSYALAVLSNYDANKTGLKE
	LPNRNLQEILHGAVRFSNNPALCNVESIQWRDIVSSDFLSNMSMDFQNHLGSCQKCDPSCPNCSCWG
	AGEENCQKLTKIICAQQCSGRCRGKSPSDCCHNQCAAGCTGPRESDCLVCRKFRDEATCKDTCPPLM
	LYNPTTYQMDVNPEGKYSFGATCVKKCPRNYVVTDHGSCVRACGADSYEMEEDGVRKCKKCEGPCRK
	VCNGIGIGEFKDSLSTNATNIKHFKNCTSISGDLHILPVAFRGDSFThTPPLDPQELDILKTVKEIT
	GFLLIQAWPENRTDLHAFENLEIIRGRTKQHGQFSLAVVSLNITSLGLRSLKEISDGDVIISCNKNL
	CYANTINWKKLFGTSGQKTKIISNRGENSCKATGQVCHALCSPEGCWGPEPRDCVSCRNVSRGRECV
	DKCKLLEGEPREFVENSECIQCHPECLPQAMNITCTGRGPDNCIQCAHYIDGPHCVKTCPAGVMGEN
	NTLVWKYADAGHVCHLCHPNCTYGCTGPGLEGCPTNGPKIPSIATGMVGALLLLLVVALGIGLFMRR
	RHIVRKRTLRRLLQERELVEPLTPSGEAPNQALLRILKETEFKKIKVLGSGAFGTVYKGLWIPEGEK
	VKIPVAIKELREATSPKANKEILDEAYVMASVDNPHVCRLLGICLTSTVQLITQLMPFGCLLDYVRE
	HKDNIGSQYLLNWCVQIAXGMNYLEDRRLVHRDLAARNVLVKTPQHVKITDFGLAKLLGAEEKEYHA
	EGGKVPIKWMALESILHRIYTHQSDVWSYGVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPI
	CTIDVYMIMVKCWMIDADSRPKFRELIIEFSKMARDPQRYLVTQGDERMHLPSPTDSNFYRALMDEE
	DMDDVVDADEYLIPQQGFFSSPSTSRTPLLSSLSATSNNSTVACIDRNGLQSCPIKEDSFLQRYSSD
	PTGALTEDSIDDTFLPVPEYINQSVPKRPAGSVQNPVYHNQPLNPAPSRDPHYQDPHSTAVGNPEYL
	NTVQFTCVNSTFDSPAHWAQKGSMQISLDNPDYQQDFFPKEAKPNGIFKGSTAENAEYLRVAPQSSE
	FIGA

[0414] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 12B.

TABLE 12B
Comparison of NOV12a against NOV12b.
	Protein	NOV12a Residues/	Identities/Similarities
	Sequence	Match Residues	for the Matched Region
	NOV12b	1 . . . 1155	1049/1210 (86%)
		1 . . . 1210	1051/1210 (86%)

[0415] Further analysis of the NOV12a protein yielded the following properties shown in Table 12C.

TABLE 12C
Protein Sequence Properties NOV12a
PSort     0.8834 probability located in plasma membrane;
analysis: 0.1000 probability located in endoplasmic
          reticulum (membrane); 0.1000 probability located
          in endoplasmic reticulum (lumen);
          0.1000 probability located in outside
SignalP   Cleavage site between residues 25 and 26
analysis:

[0416] 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 12D.

TABLE 12D
Geneseq Results for NOV12a
		NOV12a
		Residues/	Identities/
Geneseq	Protein/Organism/Length	Match	Similarities for the	Expect
Identifier	[Patent #, Date]	Residues	Matched Region	Value
AAB68420	Amino acid sequence of	1 . . . 1155	1149/1210 (94%)	0.0
	wild type EGFR1 - Homo	1 . . . 1210	1149/1210 (94%)
	sapiens, 1210 aa.
	[WO200136659-A2,
	25 MAY 2001]
AAE23019	Human Her-1 protein #1 -	1 . . . 1155	1148/1210 (94%)	0.0
	Homo sapiens, 1210 aa.	1 . . . 1210	1148/1210 (94%)
	[WO200226758-A1,
	04 APR. 2002]
AAM50768	Human epidermal growth	1 . . . 1155	1148/1210 (94%)	0.0
	factor receptor precursor -	1 . . . 1210	1148/1210 (94%)
	Homo sapiens, 1210 aa.
	[WO200198321-A1,
	27 DEC. 2001]
AAY50616	Human EGF receptor protein -	1 . . . 1155	1148/1210 (94%)	0.0
	Homo sapiens, 1210 aa.	1 . . . 1210	1148/1210 (94%)
	[US5985553-A,
	16 NOV. 1999]
AAB19259	Amino acid sequence of an	1 . . . 1155	1148/1210 (94%)	0.0
	epidermal growth factor	1 . . . 1210	1148/1210 (94%)
	receptor - Homo sapiens,
	1210 aa. [US6127126-A,
	03 OCT. 2000]

[0417] 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 12E.

TABLE 12E
Public BLASTP Results for NOV12a
		NOV12a
Protein		Residues/	Identities/
Accession		Match	Similarities for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
P00533	Epidermal growth factor	1 . . . 1155	1149/1210 (94%)	0.0
	receptor precursor (EC	1 . . . 1210	1149/1210 (94%)
	2.7.1.112) (Receptor
	protein-tyrosine kinase
	ErbB-1) - Homo sapiens
	(Human), 1210 aa.
GQHUE	epidermal growth factor	1 . . . 1155	1148/1210 (94%)	0.0
	receptor precursor - human,	1 . . . 1210	1148/1210 (94%)
	1210 aa.
Q01279	Epidermal growth factor	1 . . . 1155	1040/1212 (85%)	0.0
	receptor precursor (EC	1 . . . 1210	1091/1212 (89%)
	2.7.1.112) -Mus musculus
	(Mouse), 1210 aa.
A53183	epidermal growth factor	1 . . . 1155	1039/1212 (85%)	0.0
	receptor precursor - mouse,	1 . . . 1210	1091/1212 (89%)
	1210 aa.
Q9EP98	Epidermal growth factor	1 . . . 1155	1039/1212 (85%)	0.0
	receptor isoform 1 - Mus	1 . . . 1210	1090/1212 (89%)
	musculus (Mouse), 1210 aa.

[0418] PFam analysis predicts that the NOV12a protein contains the domains shown in the Table 12F.

TABLE 12F
Domain Analysis of NOV12a
		Identities/
		Similarities
	NOV12a	for the
	Match	Matched	Expect
Pfam Domain	Region	Region	Value
Recep_L_domain	57 . . . 180	54/133 (41%)	5.1e−59
		116/133 (87%)
Furin-like	184 . . . 338	93/183 (51%)	2e−99
		150/183 (82%)
Recep_L_domain	341 . . . 437	32/132 (24%)	2.8e−11
		74/132 (56%)
pkinase	657 . . . 910	80/294 (27%)	1e−74
		210/294 (71%)

Example 13

[0419] 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: 77	4145 bp
NOV13a,	GGCGGGCGGGCGGGCGGCTGCGAGCATGGTCCTGGTGCTGCACCACATCCTCATCGCTGTTGTCCAA
CG138130-01
DNA Sequence	TTCCTCACGCGGGGCCAGCACGTCTTCCTCAAGCCGGACGAGCCGCCGCCCCCGCCGCAGCCATGCG
	CCGACAGCCTGCAGCCAGCCTGGACCCCCTTGCAAAGGAGCCAGGACCCCCACGGAGTAGACACGAC
	CGACTGGAGGACGCCTTGCTGAGTCTGGGCTCTGTCATCGACATTTCAGGCCTGCAACGTGCTGTCA
	AGGAGGCCCTGTCAGCTGTGCTCCCCCGAGTGGAAACTGTCTACACCTACCTACTGGATGGTGAGTC
	CCAGCTGGTGTGTGAGGACCCCCCACATGAGCTGCCCCAGGAGGGGAAAGTCCGGGAGGCTATCATC
	TCCCAGAAGCGGCTGGGCTGCAATGGGCTGGGCTTCTCAGACCTGCCACGGAAGCCCTTGGCCAGGC
	TGGTGGCTCCACTGGCTCCTGATACCCAAGTGCTGGTCATGCCGCTACCGGACAAGGAGGCTGGCGC
	CGTGGCAGCTGTCATCTTGGTGCACTGTGGCCAGCTGAGTGATAATGAGGAATGGAGCCTGCAGGCG
	GTGGAGAAGCATACCCTGGTCGCCCTGCGGAGGGTGCAGGTCCTGCAGCAGCGCGGGCCCAGGGAGG
	CTCCCCGAGCCGTCCAOAACCCCCCGGAGGGGACGGCGGAAGACCAGAAGGGCGGGGCGGCGTACAC
	CGACCGCGACCGCAAGATCCTCCAACTGTGCGGGGAACTCTACGACCTGGATGCCTCTTCCCTGCAG
	CTCAAAGTGCTCCAATACCTGCAGCAGGAGACCCGGGCATCCCGCTGCTGCCTCCTGCTGGTGTCGG
	AGGACAATCTCCAGCTTTCTTGCAAGGTCATCGGAGACAAAGTGCTCGGGGAAGAGGTCAGCTTTCC
	CTTGACAGGATGCCTGGGCCAGGTGGTGGAAGACAAGAAGTCCATCCAGCTGAAGGACCTCACCTCC
	GAGGATGTACAACAGCTGCAGAGCATGTTGGGCTGTGAGCTGCAGGCCATGCTCTGTGTCCCTGTCA
	TCAGCCGGGCCACTGACCAGGTGGTGGCCTTGGCCTGCGCCTTCAACAAGCTAGAAGGAGACTTGTT
	CACCGACGAGGACGAGCATGTGATCCAGCACTGCTTCCACTACACCAGCACCGTGCTCACCAGCACC
	CTGGCCTTCCAGAAGGAACAGAAACTCAAGTGTGAGTGCCAGGCTCTTCTCCAAGTGGCAAAGAACC
	TCTTCACCCACCTGGATGACGTCTCTGTCCTGCTCCAGGAGATCATCACGGAGGCCAGAAACCTCAG
	CAACGCAGAGATCTGCTCTGTGTTCCTGCTGGATCAGAATGAGCTGGTGGCCAAGGTGTTCGACGGG
	GGCGTGGTGGATGATGAGAGCTATGAGATCCGCATCCCGGCCGATCAGGGCATCGCGGGACACGTGG
	CGACCACGGGCCACATCCTGAACATCCCTOACGCATATGCCCATCCGCTTTTCTACCGCGGCGTGGA
	CGACAGCACCGGCTTCCCCACGCGCAACATCCTCTGCTTCCCCATCAAGAACGAGAACCAGGAGGTC
	ATCGGTGTGGCCGAGCTGGTGAACAAGATCAATGGGCCATGGTTCAGCAAGTTCGACGAGGACCTGG
	CGACGGCCTTCTCCATCTACTGCGGCATCAGCATCGCCCATTCTCTCCTATACAAAAAAGTGAATGA
	GGCTCAGTATCGCAGCCACCTGGCCAATGAGATGATGATGTACCACATGAAGGTCTCCGACGATGAG
	TATACCAAACTTCTCCATGATGGGATCCAGCCTGTGGCTGCCATTGACTCCAATTTTGCAAGTTTCA
	CCTATACCCCTCCTTCCCTGCCCGAGGATGACACGTCCATGGCCATCCTGAGCATGCTCCAGGACAT
	GAATTTCATCAACAACTACAAAATTGACTGCCCGACCCTCGCCCGGTTCTGTTTOATGGTGAAGAAG
	GGCTACCGGGATCCCCCCTACCACAACTGGATGCACGCCTTTTCTGTCTCCCACTTCTGCTACCTGC
	TCTACAAGAACCTGGAGCTCACCAACTACCTCCAGGACATCGAGATCTTTGCCTTGTTTATTTCCTG
	CATGTGTCATGACCTGGACCACAGAGGCACAAACAACTCTTPCCAGGTGGCCTCGAAATCTGTGCTG
	GCTGCGCTCTACAGCTCTGAGGGCTCCGTCATGGAGAGGCACCACTTTGCTCAGGCCATCGCCATCC
	TCAACACCCACGGCTGCAACATCTTTGATCATTTCTCCCGGAAGGACTATCAGCGCATGCTGGATCT
	GATGCGGGACATCATCTTGGCCACAGACCTGGCCCACCATCTCCGCATCTTCAAGGACCTCCAGAAG
	ATGGCTGAGGTGGGCTACGACCGAAACAACAAGCAGCACCACAGACTTCTCCTCTGCCTCCTCATGA
	CCTCCTGTGACCTCTCTGACCAGACCAAGCGCTGGAAGACTACGAGAAAGATCGCGGAGCTGATCTA
	CAAAGAATTCTTCTCCCAGGGAGACCTGGAGAAGGCCATGGGCAACAGGCCGATGGAGATGATGGAC
	CGGGAGAAGGCCTATATCCCTGAGCTGCAAATCAGCTTCATGGAGCACATTGCAATGCCCATCTACA
	AGCTGTTGCAGGACCTGTTCCCCAAAGCGGCAGAGCTGTACGAGCGCGTGGCCTCCAACCGTGAGCA
	CTGGACCAAGGTGTCCCACAAGTTCACCATCCGCGGCCTCCCAAGTAACAACTCGCTGGACTTCCTG
	GATGAGGAGTACGAGGTGCCTGATCTGGATGGCACTAGGGCCCCCATCAATGGCTGCTGCAGCCTTG
	ATGCTGAGTGATCCCCTCCAGGACACTTCCCTGCCCAGGCCACCTCCCACAGCCCTCCACTGGTCTG
	GCCAGATGCACTCGGAACAGAGCCACGGGTCCTGGGTCCTAGACCAGGACTTCCTGTGTGACCCTGG
	ACAAGTACTACCTTCCTGGGCCTCAGCTTTCTCCTCTGTATAATGGAAGCAAGACTTCCAACCTCAC
	GGAGACTTTGTAATTTCCTTCTCTGAGAGCACAGGGGTGACCAATGAGCAGTGGGCCCTACTCTGCA
	CCTCTGACCACACCTTGGCAAGTCTTTCCCAAGCCATTCTTTGTCTGAGCAGCTTGATGGTTTCTCC
	TTGCCCCATTTCTGCCCCACCAGATCTTTGCTCCTTTCCCTTTGAGGACTCCCACCCTTTGGGTCTC
	CAGGATCCTCATGGAAGGGGAAGCTGAGACATCTGAGTGAGCAGAGTGTGGCATCTTGGAAACAGTC
	CTTAGTTCTGTGGGAGGACTAGAAACAGCCGCGGCGAAGGCCCCCTGAGGACCACTACTATACTGAT
	GGTGGGATTGGGACCTGGGGGATACAGGGGCCCCAGGAAGAAGCTGGCCAGAGGCGCAGCTCAGTGC
	TCTGCAGAGAGGGGCCCTGGGGAGAACCAGGATGGGATTGATGGCCAGGAGGGATCCCCGCACTGGG
	AGACAGGCCCAGGTATGAATGAGCCAGCCATGCTTCCTCCTGCCTGTGTGACGCTGGGCGAGTCTCT
	TCCCCTGTCTGGGCCAAACAGGGAGCGGGPAAGACAATCCATGCTCTAAGATCCATTTTAGATCAAT
	GTCTAAAATAGCTCTATGGCTCTGCGGAGTCCCAGCAGAGGCTATGGAATGTTTCTGCAACCCTAAG
	GCACAGAGAGCCAACCCTGAGTGTCTCAGAGGCCCCCTGAGTGTTCCCCTTGGCCTGAGCCCCTTAC
	CCATTCCTGCAGCCAGTGAGAGACCTGGCCTCAGCCTGGCAGCGCTCTCTTCAAGGCCATATCCACC
	TGTGCCCTGGGGCTTGGGAGACCCCATAGGCCGGCACTCTTGGGTCAGCCCGCCACTGGCTTCTCTC
	TTTTTCTCCGTTTCATTCTGTGTGCGTTGTGGGGTGGGGGAGGGGGTCCACCTGCCTTACCTTTCTG
	AGTTGCCTTTAGAGAGATGCGTTTTTCTAGGACTCTCTGCAACTGTCGTATATGGTCCCGTGGGCTG
	ACCGCTTTGTACATGAGAATAAATCTATTTCTTTCTACCAAAAAAAAAAAAAAAAAAA
	ORF Start: ATG at 130	ORF Stop: TGA at 2890
	SEQ ID NO: 78	920aa	MW at 103477.0kD
NOV13a,	MRRQPAASLDPLAKEPGPPOSRDDRLEDALLSLGSVIDISGLQRAVKEALSAVLPRVETVYTYLLDG
CG138130-01
Protein Sequence	ESQLVCEDPPHELPQEGKVREAIISQKRLGCNGLGESDLPGKPLARLVAPLAPDTQVLVMPLADKEA
	GAVAAVILVHCGQLSDNEEWSLQAVEKHTLVALRRVQVLQQRGPREAPRAVQNPPEGTAEDQKGGAA
	YTDRDRKILQLCGELYDLDASSLQLKVLQYLQQETRASRCCLLLVSEDMLQLSCKVIGDKVLGEEVS
	FPLTGCLGQVVEDKKSIQLKDLTSEDVQQLQSMLGCELQAMLCVPVISRATDQVVALACAFNKLEGD
	LFTDEDEBVIQHCFHYTSTVLTSTLAFQKEQKLKCECQALLQVAKNLFTHLDDVSVLLQEIITEARN
	LSNAEICSVFLLDQNELVAXVFDGGVVDDESYEIRIPADQGIAGHVATTGQILNIPDAYAHPLFYRG
	VDDSTGFRTRNILCFPIKNENQEVIGVAELVNKINGPWFSKFDEDLATAFSIYCGISIAHSLLYKKV
	NEAQYRSHLANEMMMYHMKVSDDEYTKLLHDGIQPVAAIDSNFASFTYTPRSLPEDDTSMAILSMLQ
	DMNFINNYKIDCPTLARFCLMVKKGYRDPPYHNWMHAFSVSHFCYLLYKNLELTNYLEDIEIFALFI
	SCMCHDLDHRGTNNSFQVASKSVLAALYSSEGSVMERHHFAQAIAILNTHGCNIFDHFSRKDYQRML
	DLMRDIILATDLAHHLRIFKDLQKMAEVGYDRNNKQHHRLLLCLLMTSCDLSDQTKGWKTTRKIAEL
	IYKEFFSQGDLEKAMGNRPMEMMDREKAYIPELQISFMEHIAMPIYKLLQDLFPKAAELYERVASNR
	EHWTKVSHKFTIRGLPSNNSLDFLDEEYEVPDLDGTRAPINGCCSLDAE

[0420] Further analysis of the NOV13a protein yielded the following properties shown in Table 13B.

TABLE 13B
Protein Sequence Properties NOV13a
PSort     0.4500 probability located in cytoplasm; 0.3000
analysis: 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:

[0421] 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	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAB85117	Human cGMP-stimulated	16 . . . 920	898/905 (99%)	0.0
	PDE2A3 - Homo sapiens,	37 . . . 941	899/905 (99%)
	941 aa. [EP1097707-A1,
	09 MAY 2001]
AAB85106	Human cGMP-stimulated	16 . . . 920	898/905 (99%)	0.0
	PDE2A3 sequence - Homo	37 . . . 941	899/905 (99%)
	sapiens, 941 aa.
	[EP1097706-A1,
	09 MAY 2001]
AAG66539	Human interferon-alpha	16 . . . 920	898/905 (99%)	0.0
	induced polypeptide, PDE2A -	37 . . . 941	899/905 (99%)
	Homo sapiens, 941 aa.
	[WO200159155-A2,
	16 AUG. 2001]
AAE07954	Human phosphodiesterase	16 . . . 920	898/905 (99%)	0.0
	(PDE) type 2 protein - Homo	37 . . . 941	899/905 (99%)
	sapiens, 941 aa.
	[EP1097719-A1,
	09 MAY 2001]
AAE07918	Human phosphodiesterase	16 . . . 920	898/905 (99%)	0.0
	(PDE) type 2 protein - Homo	37 . . . 941	899/905 (99%)
	sapiens, 941 aa.
	[EP1097718-A1,
	09 MAY 2001]

[0422] 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 for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
O00408	cGMP-dependent 3′,5′-cyclic	16 . . . 920	898/905 (99%)	0.0
	phosphodiesterase (EC	37 . . . 941	899/905 (99%)
	3.1.4.17) (Cyclic GMP
	stimulated
	phosphodiesterase)
	(CGS-PDE) (cGSPDE) -
	Homo sapiens (Human),
	941 aa.
P14099	cGMP-dependent 3′,5′-cyclic	1 . . . 920	873/921 (94%)	0.0
	phosphodiesterase (EC	1 . . . 921	894/921 (96%)
	3.1.4.17) (Cyclic GMP
	stimulated
	phosphodiesterase)
	(CGS-PDE) (cGSPDE) - Bos
	taurus (Bovine), 921 aa.
Q01062	cGMP-dependent 3′,5′-cyclic	1 . . . 918	835/919 (90%)	0.0
	phosphodiesterase (EC	16 . . . 927	866/919 (93%)
	3.1.4.17) (Cyclic GMP
	stimulated
	phosphodiesterase)
	(CGS-PDE) (cGSPDE) -
	Rattus norvegicus (Rat), 928
	aa.
AAH29810	Similar to cyclic GMP	407 . . . 918	507/512 (99%)	0.0
	stimulated phosphodiesterase -	1 . . . 512	512/512 (99%)
	Mus musculus (Mouse),
	513 aa (fragment).
Q922S4	cGMP-dependent 3′,5′-cyclic	555 . . . 918	359/364 (98%)	0.0
	phosphodiesterase (EC	1 . . . 364	364/364 (99%)
	3.1.4.17) (Cyclic GMP
	stimulated
	phosphodiesterase)
	(CGS-PDE) (cGSPDE) - Mus
	musculus (Mouse), 365 aa
	(fragment).

[0423] PFam analysis predicts that the NOV13a protein contains the domains shown in the Table 13E.

TABLE 13E
Domain Analysis of NOV13a
			Identities/
		NOV13a	Similarities
	Pfam	Match	for the	Expect
	Domain	Region	Matched Region	Value
	GAF	220 . . . 361	28/148 (19%)	3.8e−16
			104/148 (70%)
	GAF	388 . . . 532	45/150 (30%)	2.6e−36
			125/150 (83%)
	PDEase	634 . . . 871	119/279 (43%)	1.6e−181
			236/279 (85%)

Example 14

[0424] 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: 79	1216 bp
NOV14a,	AAGACACGGGCCTGATTCGTCGAGTCTCACTGAGCCTTAGTCGTCGGCAGGTCCCAGGCCCGAAGTT
CG138372-01
DNA Sequence	TCTCGGCCTGGAGGAGGGGGTCGCGCGAAGTGCCAGATGCAGGCGGGGAAGCCCATCCTCTATTCCT
	ATTTCCGAAGCTCCTGCTCATGGAGAGTTCGAATTGCTCTGGCCTTGAAAGGCATCGACTACAAGAC
	GGTGCCCATCAATCTCATAAAGGATGGGGGCCAACAGTTTTCTAAGGACTTCCAGGCACTGAATCCT
	ATGAAGCAGGTGCCAACCCTGAAGATTGATGGAATCACCATTCACCAGTCACTGGCCATCATTGAGT
	ATCTAGAGGAGACGCGTCCCACTCCGCGACTTCTGCCTCAGGACCCAAAGAAGAGOGCCAGCGTGCG
	TATGATTTCTGACCTCATCGCTGGTGGCATCCAGCCCCTGCAGAACCTGTCTGTCCTGAAGCAAGTG
	GGAGAGGAGATGCAGCTGACCTGGGCCCAGAACGCCATCACTTGTGGCTTTAACGCCCTGGAGCAGA
	TCCTACAGAGCACAGCGGGCATATACTGTGTAGGAGACGAGGTGACCATGGCTGATCTGTGCTTGGT
	GCCTCAGGTGGCAAATGCTGAAAGATTCAAGGTGGATCTCACCCCCTACCCTACCATCAGCTCCATC
	AACAAGAGGCTGCTGGTCTTGGAGGCCTTCCAGGTGTCTCACCCCTGCCGGCAGCCAGATACACCCA
	CTGAGCTGAGGGCCTAGCTCCCAAATCCTGCCCCGTTGGCACAGGGCCACAGGAGCAGAAGCTGGGT
	GGGCTGAAGAGGCCTGGAAACGAGAGTCTTAATTGAGGAGATGGGAGACTCGAACTCTAGCCCTGGA
	TCTGCCTTCCTGCTGAAACTTGTTCCACCTCAGTCCCCTCATCTGTCACACGCATGTGGGGTGGAGT
	AGGGAGATGCGGGGAGCAGGGTGGGCAGGAATACTGTTATCTATGTGACGGGGCAGTCGTGAGGCTG
	AGATGAGAATGCGGATTAAAATGCCTGGCGTGCTCACCGTAACACCACGGGGAAGGCTGTGTGCCTT
	TTCTCATCCGCTTTTGTTGTGTGTGACTCCAAAGAATGCCCGCGCTGAAATTTGGCGTGAATTAAAC
	TGAAGCCCAGGCCTCTAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA
	AAAAAAAAAA
	ORF Start ATG at 104	ORF Stop: TAG at 752
	SEQ ID NO: 80	216 aa	MW at 24082.7kD
NOV14a,	MQAGKPILYSYFRSSCSWRVRIALALKGIDYKTVPINLIKDGGQQFSKDFQALNPMKQVPTLKIDGI
CG138372-01
Protein Sequence	TIHQSLAIIEYLEETRPTPRLLPQDPKKRASVRMTSDLIAGGIQPLQNLSVLKQVGEEMQLTWAQNA
	ITCGFNALEQILQSTAGIYCVGDEVTMADLCLVPQVANAERFKVDLTPYPTISSINKRLLVLEAFQV
	SHPCRQPDTPTELRA
	SEQ ID NO: 81	579 bp
NOV14b,	GTCGCGCGAAGTGCCAGATGCAGGCGGGGAAGCCCATCCTCTATTCCTATTTCCGAAGCTCCTGCTC
CG138372-01
DNA Sequence	ATGGAGAGTTCGAATTGCTCTGGCCTTGAAAGGCATCGACTACGACACGGTGCCCATCAATCTCATA
	AAGGATGGGGGCCAACAGTTTTCTAAGGACTTCCAGGCACTGAATCCTATGAAGCAGGTGCCAACCC
	TGAAGATTGATGGAATCACCATTCACCAGTCAAACCTGTCTGTCCTGAAGCAAGTGGGAGAGGAGAT
	GCAGCTGACCTGGGCCCAGAACGCCATCACTTGTCGCTTTAACGCCCTGGAGCAGATCCTACAGAGC
	ACAGCGGGCATATACTGTGTAGGAGACGAGGTGACCATGGCTGATCTGTGCTTGGTCCCTCAGGTGG
	CAAATGCTGAAAGATTCAAGGTGGATCTCACCCCCTACCCTACCATCAGCTCCATCAACAAGAGGCT
	GCTGGTCTTGGAGGCCTTCCACGTGTCTCACCCCTGCCGGCAGCCAGATACACCCACTGAGCTGAGG
	GCCTAGCTCCCAAATCCTGCCCCGTTGGCACAGGGCCACAGGA
	ORF Start: ATG at 18	ORF Stop: TAG at 540
	SEQ ID NO: 82	174 aa	MW at 19382.2kD
NOV14b,	MQAGKPILYSYFRSSCSWRVRIALALKGIDYETVPINLIKDCGQQFSKDFQALNPMKQVPTLKIDGI
CG138372-02
Protein Sequence	TIHQSNLSVLKQVGEEMQLTWAQNAITCGFNALEQILQSTAGIYCVGDEVTMADLCLVPQVANAERF
	KVDLTPYPTISSINKRLLVLEAFHVSHPCRQPDTPTELRA
	SEQ ID NO: 83	1216 bp
NOV14c,	AAGACACGGGCCTGATTCGTCGAGTCTCACTGAGCCTTAGTCGTCGGCAGGTCCCAGGCGCGAACTT
CG138372-01
DNA Sequence	TCTCGGCCTGGAGGAGGGGGTCGCGCGAAGTGCCAGATGCAGGCGGGGAAGCCCATCCTCTATTCCT
	ATTTCCGAAGCTCCTGCTCATGGAGAGTTCGAATTGCTCTGGCCTTGAAAGGCATCGACTACAAGAC
	GGTGCCCATCAATCTCATAAAGGATGGGGCCCAACAGTTTTCTAAGGACTTCCACGCACTGAATCCT
	ATGAAGCAGGTGCCAACCCTOAAGATTGATGGAATCACCATTCACCAGTCACTGGCCATCATTGAGT
	ATCTAGAGGAGACGCGTCCCACTCCGCGACTTCTGCCTCAGGACCCAAAGAAGAGGGCCAGCGTGCG
	TATGATTTCTGACCTCATCGCTGGTGGCATCCAGCCCCTGCAGAACCTGTCTGTCCTGAAGCAAGTG
	GGAGAGGAGATGCAGCTGACCTGGGCCCAGAACGCCATCACTTGTGGCTTTAACGCCCTGGAGCAGA
	TCCTACAGAGCACAGCGGGCATATACTGTGTAGGAGACGAGGTGACCATGGCTGATCTGTGCTTGGT
	GCCTCAGGTGGCAAATGCTGAAAGATTCAAGGTGGATCTCACCCCCTACCCTACCATCAGCTCCATC
	AACAAGAGGCTGCTGGTCTTGCAGGCCTTCCAGGTGTCTCACCCCTGCCGGCAGCCAGATACACCCA
	CTGAGCTGAGGGCCTAGCTCCCAAATCCTGCCCCGTTGGCACAGGGCCACAGGAGCAGAAGCTGGGT
	GGGCTGAAGAGGCCTGGAAACGAGAGTCTTAATTGAGGAGATGGGAGACTCGAACTCTAGCCCTGGA
	TCTGCCTTCCTGCTGAAACTTGTTCCACCTCAGTCCCCTCATCTGTCACACGCATGTGGGGTGGAGT
	AGGGAGATGCGGGCAGCAGGGTGGCCACGAATACTGTTATCTATGTGACGGGGCAGTCGTGAGGCTG
	AGATGAGAATGCGGATTAAAATGCCTGGCGTGCTCACCGTAACACCACGGGGAAGGCTGTGTGCCTT
	TTCTCATCCGCTTTTGTTGTGTGTCACTCCAAAGAATGCCCGCGCTGAAATTTGGCGTGAATTAAAC
	TGAAGCCCAGGCCTCTAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA
	AAAAAAAAAA
	ORF Start: ATG at 104	ORF Stop: TAG at 752
	SEQ ID NO: 84	216 aa	MW at 24082.7kD
NOV14c,	MQAGKPILYSYFRSSCSWRVRIALALKGIDYKTVPINLIKDGGQQFSKDFQALNPMKQVPTLKIDGI
CG138372-01
Protein Sequence	TIHQSLAITEYLEETRPTPRLLPQDPKKRASVEMISDLIAGGIQPLQNLSVLKQVGEEMQLTWAQNA
	ITCGFNALEQILQSTAGIYCVGDEVTMADLCLVPQVANAERFKVDLTPYPTISSINKRLLVLEAFQV
	SHPCRQPDTPTELRA
	SEQ ID NO: 85	159 bp
NOV14d,	CACCGGATCCACCATGCAGGCGGGGAAGCCCATCCTCTATTCCTATTTCCGAAGCTCCTGCTCATGG
277582121 DNA
Sequence	AGAGTTCGAATTGCTCTGGCCTTGAAAGGCATCGACTACGAGACGGTGCCCATCAATCTCATAAAGG
	ATGGGGGCCAACAGTTTTCTAAGGACTTCCAGCCACTGAATCCTATGAAGCACGTGCCAACCCTGAA
	GATTGATGGAATCACCATTCACCAGTCAAACCTGTCTGTCCTGAAGCAAGTGGGAGAGGAGATGCAG
	CTGACCTGGGCCCAGAACGCCATCACTTGTGGCTTTAACGCCCTGGAGCAGATCCTACAGAGCACAG
	CGGGCATATACTGTGTAGGAGACOAGGTGACCATCGCTGATCTGTGCTTGGTGCCTCAGGTGGCAAA
	TGCTGAAAGATTCAAGGTGGATCTCACCCCCTACCCTACCATCAGCTCCATCAACAAGAGGCTGCTG
	GTCTTGGAGGCCTTCCAGGTGTCTCACCCCTGCCGGCAGCCAGATACACCCACTGAGCTGAGGGCCC
	TCGAGGGC
	ORF Start: at 2	ORF Stop: end of sequence
	SEQ ID NO: 86	181 aa	MW at 20018.8kD
NOV14d,	TGSTMQAGKPILYSYFRSSCSWRVRIALALKGIDYETVPINLIKDGGQQFSKDFQALNPMKQVPTLK
277582121
Protein Sequence	IDGITIHQSNLSVLKQVGEEMQLTWAQNAITCGFNALEQILQSTAGIYCVGDEVTMADLCLVPQVAN
	AERFKVDLTPYPTISSINKRLLVLEAFQVSHPCRQPDTPTELRALEG
	SEQ ID NO: 87	720 bp
NOV14e,	GTCGCGCGAAGTGCCAGATGCAGGCGGGGAAGCCCATCCTCTATTCCTATTTCCGAAGCTCCTGCTC
CG138372-03
DNA Sequence	ATGGAGAGTTCGAATTGCTCTGGCCTTGAAAGGCATCGACTACGAGACGGTGCCCATCAATCTCATA
	AAGGATGGGGGCCAACAGTTTTCTAAGGACTTCCAGGCACTGAATCCTATGAAGCAGGTGCCAACCC
	TGAAGATTGATGGAATCACCATTCACCAGTCACTGGCCATCATTGAGTATCTAGAGGAGACGCGTCC
	CACTCCGCGACTTCTGCCTCAGGACCCAAAGAAGAGGGCCAGCGTGCGTATGATTTCTGACCTCATC
	GCTGGTGGCATCCAGCCCCTGCAGAACCTGTCTGTCCTGAAGCAAGTGGGAGAGGAGATGCAGCTGA
	CCTGGGCCCAGAACGCCATCACTTGTGGCTTTAACGCCCTGGAGCAGATCCTACAGAGCACAGCGGG
	CATATACTGTGTAGGAGACGAGGTGACCATCGCTGATCTGTGCTTGGTGCCTCAGGTGGCAAATGCT
	GAAAGATTCAAGGTGGATCTCACCCCCTACCCTACCATCAGCTCCATCAACAAGAGGCTGCTGGTCT
	TGGAGCCCTTCCAGGTGTCTCACCCCTGCCGGCAGCCAGATACACCCACTGAGCTGAGGGCCTAGCT
	CCCAAATCCTGCCCCGTTGGCACACGGCCACAGGAGCAGAAGAAGGGCGA
	ORF Start: ATG at 18	ORF Stop: TAG at 666
	SEQ ID NO: 88	216 aa	MW at 24083.7kD
NOV14e,	MQAGKPILYSYFRSSCSWRVRIALALKGIDYETVPINLIKDGGQQFSKDFQALNPMKQVPTLKIDGI
CG138372-03
Protein Sequence	TIHQSLAIIEYLEETRPTPRLLPQDPKKRASVRMISDLIAGGIQPLQNLSVLKQVGEEMQLTWAQNA
	ITCGFNALEQILQSTAGIYCVGDEVTMADLCLVPQVANAERFKVDLTPYPTISSINKRLLVLEAFQV
	SHPCRQPDTPTELRA

[0425] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 14B.

TABLE 14B
Comparison of NOV14a against NOV14b through NOV14e.
			Identities/
			Similarities
	Protein	NOV14a Residues/	for the
	Sequence	Match Residues	Matched Region
	NOV14b	1 . . . 216	172/216 (79%)
		1 . . . 174	173/216 (79%)
	NOV14c	1 . . . 216	216/216 (100%)
		1 . . . 216	216/216 (100%)
	NOV14d	1 . . . 216	173/216 (80%)
		5 . . . 178	174/216 (80%)
	NOV14e	1 . . . 216	215/216 (99%)
		1 . . . 216	216/216 (99%)

[0426] Further analysis of the NOV14a protein yielded the following properties shown in Table 14C.

TABLE 14C
Protein Sequence Properties NOV14a
PSort     0.4856 probability located in mitochondrial
analysis: matrix space; 0.3000 probability located in
          nucleus; 0.2246 probability located in
          lysosome (lumen); 0.1962 probability located in
          mitochondrial inner membrane
SignalP   No Known Signal Sequence Predicted
analysis:

[0427] A search of the NOV14a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 14D.

TABLE 14D
Geneseq Results for NOV14a
			Identities/
			Similarities for
Geneseq	Protein/Organism/Length	NOV14a Residues/	the Matched	Expect
Identifier	[Patent #, Date]	Match Residues	Region	Value
ABB64377	Drosophila melanogaster	3 . . . 213	123/212 (58%)	3e−68
	polypeptide SEQ ID NO	31 . . . 242	160/212 (75%)
	19923 - Drosophila
	melanogaster, 246 aa.
	[WO200171042-A2,
	27 SEP. 2001]
ABB64379	Drosophila melanogaster	5 . . . 214	126/210 (60%)	2e−66
	polypeptide SEQ ID NO	15 . . . 224	155/210 (73%)
	19929 - Drosophila
	melanogaster, 227 aa.
	[WO200171042-A2,
	27 SEP. 2001]
AAG43196	Arabidopsis thaliana protein	8 . . . 212	100/210 (47%)	2e−47
	fragment SEQ ID NO: 53962 -	11 . . . 218	137/210 (64%)
	Arabidopsis thaliana, 221
	aa. [EP1033405-A2,
	06 SEP. 2000]
AAG43195	Arabidopsis thaliana protein	8 . . . 212	100/210 (47%)	2e−47
	fragment SEQ ID NO: 53961 -	27 . . . 234	137/210 (64%)
	Arabidopsis thaliana, 237
	aa. [EP1033405-A2,
	06 SEP. 2000]
AAG10203	Arabidopsis thaliana protein	8 . . . 212	98/210 (46%)	4e−46
	fragment SEQ ID NO: 8428 -	11 . . . 218	134/210 (63%)
	Arabidopsis thaliana, 221 aa.
	[EP1033405-A2,
	06 SEP. 2000]

[0428] 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 14E.

TABLE 14E
Public BLASTP Results for NOV14a
			Identities/
Protein			Similarities for
Accession		NOV14a Residues/	the Matched	Expect
Number	Protein/Organism/Length	Match Residues	Portion	Value
O43708	Maleylacetoacetate isomerase	1 . . . 216	215/216 (99%)	e−120
	(EC 5.2.1.2) (MAAI)	1 . . . 216	215/216 (99%)
	(Glutathione S- transferase
	zeta 1) (EC 2.5.1.18)
	(GSTZ1-1) - Homo sapiens
	(Human), 216 aa.
Q9WVL0	Maleylacetoacetate isomerase	1 . . . 215	184/215 (85%)	e−102
	(EC 5.2.1.2) (MAAI)	1 . . . 215	196/215 (90%)
	(Glutathione S- transferase
	zeta 1) (EC 2.5.1.18)
	(GSTZ1-1) - Mus musculus
	(Mouse), 216 aa.
Q9VHD3	Probable maleylacetoacetate	3 . . . 213	123/212 (58%)	8e−68
	isomerase 1 (EC 5.2.1.2)	31 . . . 242	160/212 (75%)
	(MAAI 1) - Drosophila
	melanogaster (Fruit fly), 246
	aa.
Q9VHD2	Probable maleylacetoacetate	5 . . . 214	126/210 (60%)	6e−66
	isomerase 2 (EC 5.2.1.2)	15 . . . 224	155/210 (73%)
	(MAAI 2) - Drosophila
	melanogaster (Fruit fly), 227
	aa.
AAM61889	Glutathione S-transferase -	5 . . . 213	123/209 (58%)	4e−65
	Anopheles gambiae (African	11 . . . 219	156/209 (73%)
	malaria mosquito), 222 aa.

[0429] PFam analysis predicts that the NOV14a protein contains the domains shown in the Table 14F.

TABLE 14F
Domain Analysis of NOV14a
			Identities/
		NOV14a	Similarities for
	Pfam	Match	the Matched	Expect
	Domain	Region	Region	Value
	GST_N	3 . . . 81	27/88 (31%)	1.5e−20
			65/88 (74%)
	GST_C	90 . . . 197	29/121 (24%)	1.1e−05
			75/121 (62%)

Example 15

[0430] 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: 89	891 bp
NOV15a,	ACCATGTATTTCCTGACTCCCATCTTGGTAGCCATTCTCTGCATTTTGGTTGTGTGGATCTTTAAAA
CG138461-01
DNA Sequence	ATGCCGACAGAAGCATGGAGAAAAAGAAGGGGGAGCCTAGAACCAGGGCCGAAGCTCGCCCCTGGGT
	GGATGAAGACTTAAAAGACAGCAGTOACCTGCACCAAGCAGAAGAAGATGCTGATGAATGGCAAGAA
	TCAGAAGAAAATGTTGAACACATCCCCTTCTCTCATAACCACTATCCTGAGAAGGAAATGGTTAAGA
	GGTCTCAGGAATTTTATGAACTTCTCAATAAGAGACGGTCAGTCAGGTTCATAAGTAATGAGCAAGT
	CCCAATGGAAGTCATTGATAATGTCATCAGAACGGCAGGTACAGCCCCGAGTGGGGCTCACACAGAG
	CCCTGGACCTTCGTGGTTGTGAAGGACCCAGACGTGAAGCACAAGATTCGAAAGATCATTGAGGAGG
	AAGAGGAGATCAACTACATGAAAAGGATGGGACATCGCTGGGTCACAGACCTCAAGAAACTGAGAAC
	CAACTGGATTAAAGAGTACTTGGATACTGCCCCTATTTTGATTCTCATTTTCAAACAAGTACATGGT
	TTCGCCGCAAATGGCAAGAAAAAAGTCCACTACTACAATGAGATCAGTGTTTCCATCGCTTGTGGCA
	TCCTGCTAGCTGCCCTGCAGAATGCAGGTCTGGTGACTGTCACTACCACTCCTCTCAACTGTGGCCC
	TCGACTGAGGGTGCTCCTGGGCCGCCCCGCACATGAAAAGCTGCTGATGCTGCTCCCCGTGGGGTAC
	CCCAGCAAGGAGGCCACGGTGCCTGACCTCAAGCGCAAACCTCTGGACCAGATCATGGTGACAGTGT
	AGGCACGGCCCCCCAAGGGA
	ORF Start: ATG at 4	ORF Stop: TAG at 871
	SEQ ID NO: 90	289 aa	MW at 33359.3kD
NOV15a,	MYFLTPILVAILCILVVWIFKNADRSMEKKKGEPRTRAEARPWVDEDLKDSSDLHQAEEDADEWQES
CG138461-01
Protein Sequence	EENVEHIPFSHNHYPEKEMVKRSQEFYELLNKRRSVRFISNEQVPMEVIDNVIRTAGTAPSGAUTEP
	WTFVVVKDPDVKHKIRKIIEEEEEINYNKRMGHRWVTDLKKLRTNWIKEYLDTAPILILIFKQVHGF
	AANGKKKVHYYNETSVSIACGILLAALQNAGLVTVTTTPLNCGPRLRVLLGRPAHEKLLMLLPVGYP
	SKEATVPDLKRKPLDQIMVTV

[0431] Further analysis of the NOV15a protein yielded the following properties shown in Table 15B.

TABLE 15B
Protein Sequence Properties NOV15a
PSort     0.8200 probability located in endoplasmic reticulum
analysis: (membrane); 0.1900 probability located in plasma
          membrane; 0.1080 probability located in nucleus;
          0.1000 probability located in endoplasmic reticulum
          (lumen)
SignalP   Cleavage site between residues 24 and 25
analysis:

[0432] 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
			Identities/
			Similarities for
Geneseq	Protein/Organism/Length	NOV15a Residues/	the Matched	Expect
Identifier	[Patent #, Date]	Match Residues	Region	Value
AAM39746	Human polypeptide SEQ ID	1 . . . 289	289/289 (100%)	e−169
	NO 2891 - Homo sapiens,	1 . . . 289	289/289 (100%)
	289 aa. [WO200153312-A1,
	26 JUL. 2001]
ABG27497	Novel human diagnostic	42 . . . 289	236/259 (91%)	e−134
	protein #27488 - Homo	146 . . . 404	240/259 (92%)
	sapiens, 404 aa.
	[WO200175067-A2,
	11 OCT. 2001]
ABG26409	Novel human diagnostic	45 . . . 287	224/243 (92%)	e−128
	protein #26400 - Homo	166 . . . 404	227/243 (93%)
	sapiens, 404 aa.
	[WO200175067-A2,
	11 OCT. 2001]
ABG26408	Novel human diagnostic	1 . . . 167	167/167 (100%)	2e−95
	protein #26399 - Homo	2 . . . 168	167/167 (100%)
	sapiens, 168 aa.
	[WO200175067-A2,
	11 OCT. 2001]
ABG27496	Novel human diagnostic	1 . . . 156	155/156 (99%)	6e−88
	protein #27487 - Homo	2 . . . 157	156/156 (99%)
	sapiens, 157 aa.
	[WO200175067-A2,
	11 OCT. 2001]

[0433] 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
			Identities/
Protein			Similarities for
Accession		NOV15a Residues/	the Matched	Expect
Number	Protein/Organism/Length	Match Residues	Portion	Value
Q9DCX8	0610009AO7Rik protein	1 . . . 289	245/289 (84%)	e−144
	(RIKEN cDNA 0610009A07	1 . . . 285	271/289 (92%)
	gene) - Mus musculus
	(Mouse), 285 aa.
O75989	DJ422F24.1 (Putative novel	74 . . . 257	184/184 (100%)	e−105
	protein similar to C. elegans	1 . . . 184	184/184 (100%)
	C02C2.5) - Homo sapiens
	(Human), 184 aa (fragment).
Q8T3Q0	AT19107p - Drosophila	44 . . . 288	137/247 (55%)	3e−68
	melanogaster (Fruit fly), 287	49 . . . 286	173/247 (69%)
	aa.
Q9VTE7	CG6279 protein - Drosophila	44 . . . 288	137/247 (55%)	5e−68
	melanogaster (Fruit fly), 748	510 . . . 747	174/247 (69%)
	aa.
Q9XAG5	Putative oxidoreductase -	74 . . . 282	87/210 (41%)	2e−40
	Streptomyces coelicolor, 226	9 . . . 217	124/210 (58%)
	aa.

[0434] PFam analysis predicts that the NOV15a protein contains the domains shown in the Table 15E.

TABLE 15E
Domain Analysis of NOV15a
			Identities/
		NOV15a	Similarities for
	Pfam	Match	the Matched	Expect
	Domain	Region	Region	Value
	Nitroreductase	92 . . . 254	39/182 (21%)	1.3e−13
			113/182 (62%)

Example 16

[0435] 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: 91	1787 bp
NOV16a,	TTCATTCTCAGCACTACAATCTCAGTCATTATCCCTCTGAGCTGCTCAATTACTCCCTGTCTTTTCC
CG138529-01
DNA Sequence	TCAATTTACCTAGGTGGTTCCCTGTCTGACCCAAATGCTAGGCCGATTTCPACCCTTCTCCTTGGTC
	CGGAGTTTCAGACTGCGATTTGGAGCCTGCTGCTATCCAAACCAAAAATGTGCTACTCAGACCATCA
	GACCCCCTGACTCCAGGTGCCTAGTCCAAGCAGTTTCTCAGAACTTTAATTTTGCAAAGGATGTGTT
	GGATCAGTGGTCCCAGCTGGAAAAGGTAGACGGACTCAGAGGGCCTTACCCCGCCCTCTGGAAGGTT
	AGTGCCAAAGGAGAAGAGGACAAATGGAGCTTTGAAAGGATGACTCAACTCTCCAAGAAGGCCGCCA
	GCATCCTCTCACACACCTGTGCCCTTAGCCATGGAGACCGGCTGATGATAATCTTGCCCCCAACACC
	TCAACCCTACTGGATCTGCCTGGCCTGTGTGCGCTTGGGTATCACCTTTGTGCCTGGGAGCCCCCAG
	CTGACTGCCAAGAAAATTCGCTATCAATTACGCATGTCTAAGGCCCAGTGCATTGTGGCTAATGAAG
	CTATGGCCCCAGTTGTAAACTCTGCCGTGTCCGACTGCCCCACCTTGAAAACCAAGCTCCTGGTGTC
	AGATAAGAGCTATCATGGGTGGTTGGATTTCAAGAAGTTGATTCAGGTTGCCCCTCCAAAGCAGACC
	TACATGAGGACCAAAAGCCAAGATCCAATCGCCATATTCTTCACCAAGGGTACAACAGCAGCTCCCA
	AAATGGTCGAGTATTCCCAGTATGGTTTGGGAATGGGATTCAGCCACGCTTCCAGGTACTGGATGGA
	TCTCCAGCCAACAGATGTCTTGTGGAGTCTGGGTGATGCCTTTGGTGGATCTTTATCCCTGAGCGCT
	GTCTTGGGAACTTGGTTCCAAGGAGCCTGTGTGTTTCTGTGTCACATGCCAACCTTCTGCCCTGAGA
	CTGTTCTAAATGTAAGATCAATTCCTAGTGTGGAATGTGTGGGACAAAGGCCAGAGAGAGGCATTAG
	CAATGACCCAGTGACTAGCTACAGATTCAAGAGTCTGAAGCAGTGTGTGGCTGCAGGAGCACCCATC
	AGCCCTGGGGTGATTGAGGACTGGAAACGCATCACTAAGTTGGACATCTATGAAGGCTATGGGCAGA
	CGCAAACTGTAGGTCTCTGTGCCACTTCCAAAACAATAAAATTGAAGCCAAGCTCTCTGGGGAAGCC
	ATTGCCACCTTATATTGTCCAGCAGATTGTGGATGAAAACTCAAATCTCCTGCCTCCAGGGGAAGAA
	GGAAATATTGCAATCCGCATAAAACTAAACCAACCTGCTTCTCTGTACTGTCCACACATGGTAAGAA
	AATTTTCTGCTTCAGCAAGAGGCCACATGCTTTACCTCACAGGTGACAGAGGGATCATGGATGAAGA
	CGGCTACTTCTGGTGGTCTGGTAGAGTTGATGATGTTGCCAATGCATTGGGTCAGAGATTGAATGCC
	AACCAACACCCCAGCTTATCTGAGGTCAGCATAGTTACACACCTAGTTTGTACTCCCATTCTGCAGG
	TGGTGAAGCCCCCTAATGTCCTGACTCCACAGTTCCTGTCCCATGACCAGGGCCAGCTCACCAAAGA
	GCTATAGCAGCACATAAAGTCAGTGACAGGCCCATGCAAGTACCAAAGGAAGGTGGAGTTTGTCCCA
	GAGCTGCCAAAAACCGTCACTCGCAAGATTAAACGGGAACTTCAA
	ORF Start: ATG at 102	ORF Stop: TAG at 1680
	SEQ ID NO: 92	526 aa	MW at 58238.8kD
NOV16a,	MLGRFQPFSLVRSFRLGFCACCYPWQKCATQTIRPPDSRCLVQAVSQNFNFAKDVLDQWSQLEKVDG
CG138529-01
Protein Sequence	LRGPYPALWKVSAKGEEDKWSFERMTQLSKKAASILSDTCALSHGDRLMIILPPTPEAYWICLACVR
	LGITFVPGSPQLTAKKIRYQLRMSKAQCIVANEANAPVVNSAVSDCPTLKTKLLVSDKSYDGWLDFK
	KLIQVAPPKQTYMRTKSQDPMAIFFTKGTTGAPKMVEYSQYGLGMGFSQASRYWMDLQPTDVLWSLG
	DAFGGSLSLSAVLGTWFQGACVFLCHMPTFCPETVLNVRSIPSVECVGQRPERCISNDPVTSYREKS
	LKQCVAAGGPISPGVIEDWKRITKLDIYEGYGQTETVGLCATSKTIKLKPSSLGKPLPPYIVQQIVD
	ENSNLLPPGEEGNIAIRIKLNQPASLYCPHMVRKFSASARGHHLYLTGDRGIMDEDGYFWWSGRVDD
	VANALGQRLNANQHPSLSEVSIVTHLVCTPILQVVKPPNVLTPQFLSHDQGQLTKEL

[0436] Further analysis of the NOV16a protein yielded the following properties shown in Table 16B.

TABLE 16B
Protein Sequence Properties NOV16a
PSort     0.4993 probability located in mitochondrial
analysis: matrix space; 0.2177 probability located in
          mitochondrial inner membrane; 0.2177
          probability located in mitochondrial
          intermembrane space; 0.2177 probability
          located in mitochondrial outer membrane
SignalP   Cleavage site between residues 22 and 23
analysis:

[0437] 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
			Identities/
			Similarities for
Geneseq	Protein/Organism/Length	NOV16a Residues/	the Matched	Expect
Identifier	[Patent #, Date]	Match Residues	Region	Value
ABB53263	Human polypeptide #3 -	1 . . . 526	480/539 (89%)	0.0
	Homo sapiens, 583 aa.	1 . . . 534	489/539 (90%)
	[WO200181363-A1,
	01 NOV. 2001]
ABB53262	Human polypeptide #2 -	1 . . . 478	450/482 (93%)	0.0
	Homo sapiens, 480 aa.	1 . . . 480	455/482 (94%)
	[WO200181363-A1,
	01 NOV. 2001]
AAE22093	Human kidney specific renal	43 . . . 526	204/496 (41%)	e−103
	cell carcinoma (KSRCC)	38 . . . 527	304/496 (61%)
	protein - Homo sapiens, 577
	aa. [WO200216595-A2,
	28 FEB. 2002]
AAB43245	Human ORFX ORF3009	49 . . . 526	203/490 (41%)	e−102
	polypeptide sequence SEQ	4 . . . 487	302/490 (61%)
	ID NO: 6018 - Homo sapiens,
	537 aa. [WO200058473-A2,
	05 OCT. 2000]
AAM41894	Human polypeptide SEQ ID	258 . . . 526	107/281 (38%)	6e−45
	NO 6825 - Homo sapiens,	7 . . . 283	163/281 (57%)
	390 aa. [WO200153312-A1,
	26 JUL. 2001]

[0438] 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
			Identities/
Protein			Similarities for
Accession		NOV16a Residues/	the Matched	Expect
Number	Protein/Organism/Length	Match Residues	Portion	Value
O60363	SA gene - Homo sapiens	45 . . . 526	225/494 (45%)	e−120
	(Human), 578 aa.	46 . . . 534	318/494 (63%)
Q13732	SA SA gene product precursor -	45 . . . 526	222/494 (44%)	e−118
	Homo sapiens (Human), 578	46 . . . 534	315/494 (62%)
	aa.
Q91WI1	SA rat hypertension-associated	45 . . . 526	215/494 (43%)	e−113
	homolog (SA protein) - Mus	46 . . . 534	314/494 (63%)
	musculus (Mouse), 578 aa.
Q9Z2F3	SA protein - Mus musculus	45 . . . 526	215/494 (43%)	e−113
	(Mouse), 578 aa.	46 . . . 534	314/494 (63%)
Q9Z2X0	SA - Mus musculus (Mouse),	45 . . . 526	214/495 (43%)	e−111
	578 aa.	46 . . . 534	312/495 (62%)

[0439] PFam analysis predicts that the NOV16a protein contains the domains shown in the Table 16E.

TABLE 16E
Domain Analysis of NOV16a
		Identities/
	NOV16a	Similarities
	Match	for the	Expect
Pfam Domain	Region	Matched Region	Value
AMP-binding	88 . . . 297	41/212 (19%)	9.9e−25
		136/212 (64%)
AMP-binding	334 . . . 419	25/89 (28%)	5e−13
		62/89 (70%)
AMP-binding	447 . . . 477	14/31 (45%)	0.0025
		23/31 (74%)

Example 17

[0440] 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:93	1574 bp
NOV 17a,	TCGGCCTTCCGAAACACCCCCGGGCCGGGGCACGGAGAGAGCCGAGCGCCGCAGCCGTGAGCCGAAT
CG138563-01
DNA Sequence	AGAGCCGGAGAGACCCGAGTATGACCGGAGAAGCCCAGGCCGGCCCGAAGAGGAGCCGAGCGCGGCC
	GGAAGGAACCGAGCCCGTCCGAAGGGAGCGGACGCAGCCTGGCCTGGGGCCCGGTCGAGCCCGCGCC
	ATGGCGGCCGAGGCGACAGCTGTGGCCGGAAGCGGGGCTGTTCGCGGCTGCCTGGCCAAAGACGGCT
	TGCAGCAGTCTAAGTGCCCGGACACTACCCCAAAACGGCCGCGCGCCTCGTCGCTGTCGCGTGACGC
	CGAGCGCCGAGCCTACCAATGGTGCCGGGAGTACTTGGGCGGGGCCTGGCGCCGAGTGCAGCCCGAG
	GAGCTGAGGGTTTACCCCGTGAGCGGAGGCCTCAGCAACCTGCTCTTCCGCTGCTCGCTCCCGGACC
	ACCTGCCCAGCGTTGGCGAGGAGCCCCGGGAGGTGCTTCTGCGGCTGTACGGAGCCATCTTGCAGGG
	CGTGGACTCCCTGGTGCTAGAAAGCGTGATGTTCGCCATACTTGCGGAGCGGTCGCTGGCCCCCCAG
	CTGTACGGAGTCTTCCCAGAGGGCCGGCTGGAACAGTACATCCCAAGTCGGCCATTGAAAACTCAAG
	AGCTTCGAGAGCCAGTGTTGTCAGCAGCCATTGCCACGAAGATGGCGCAATTTCATGGCATGGAGAT
	GCCTTTCACCAAGGAGCCCCACTGGCTGTTTGGGACCATGGAGCGGTACCTAAAACAGATCCAGGAC
	CTGCCCCCAACTGGCCTCCCTGAGATGAACCTGCTGGAGATGTACAGCCTGAAGGATGAGATGGGCA
	ACCTCAGGAAGTTACTAGAGTCTACCCCATCGCCAGTCGTCTTCTGCCACAATGACATCCAGGAAGG
	TAGGAGAAGGCATCTGAGTCTCCTAACCCAAGATGGAAGAGCCAGAGGGCTCTGGAGTGAGCAGAAC
	CTCACCCCATTCCCCCAGGGAACATCTTGCTGCTCTCAGAGCCAGAAAATGCTGACAGCCTCATGCT
	GGTGGACTTCGAGTACAGCAGTTATAACTATAGTTGCATTTTATTCGTCATTACCTGGCAGAGGCAA
	AGAAACGTGAGACCCTCTCCCAAGAGGAGCAGAGAAAACTGGAAGAAGATTTGCTGGTAGAAGTCAG
	TCGGTATGCTCTGGCATCCCATTTCTTCTGGGGTCTGTGGTCCATCCTCCAGGCATCCATGTCCACC
	ATAGAATTTGGTTACTTCGACTATGCCCAGTCTCGGTTCCAGTTCTACTTCCAGCAGAAGGGGCAGC
	TGACCAGTGTCCACTCCTCATCCTGACTCCACCCTCCCACTCCTTGGATTTCTCCTGGAGCCTCCAG
	GGCAGGACCTTGGAGGGAGGAACAACGAGCAGAAGGCCCTGGCGACTGGGCTGAGCCCCCAAGTGAA
	ACTGAGGTTCAGGAGACCGGCCTGTTCCTGAGTTTGAGTAGGTCCCCATGGCTGGCAGGCCAGAGCC
	CCGTGCTGTGTATGTAACACAATAAACAAGCTG
	ORE Start: ATG at 88		ORE Stop: TGA at 1147
	SEQ ID NO: 94	353 aa	MW at 39344.7 kD
NOV 17a,	MTGEAQAGRXRSRARPEGTEPVRRERTQPGLGPGRARANAAEATAVAGSGAVGGCLAKDGLQQSKCP
CG138563-01
Protein Sequence	DTTPKRRRASSLSRDAERRAYQWCREYLGGAWRRVQPEELRVYPVSGGLSNLLFRCSLPDHLPSVGE
	EPREVLLRLYGAILOGVDSLVLESVMFAILAERSLGPOLYGVFPEGRLEOYIPSRPLKTOELREPVL
	SAAIATKMAQFHGMEMPFTKEPHWLFGTMERYLKQIQDLPPTGLPEMMLLEMYSLKDEMGNLRKLLE
	STPSPVVFCHNDIQEGRRRHLSLLTQDGRARGLWSEQNLTPFPQGTSCCSQSQKMLTASCWWTSSTA
	VITIVAFYSSLPGRGKER
	SEQ ID NO:95	1540 bp
NOV 17b,	AGCCGAATAGAGCCGGAGAGACCCGAGTATGACCGGAGAAGCCCAGGCCGGCCGGAAGAGGAGCCGA
CG138563-02
DNA Sequence	GCGCGGCCGGAAGGAACCGAGCCCGTCCGAAGGGAGCGGAGCGCAGCCTGGCCTGGGGCCCGGTCGA
	GCCCGCGCCATGGCGGCCGAGGCGACAGCTGTGGCCGGAAGCGGGGCTGTTGGCGGCTGCCTGGCCA
	AAGACGGCTTGCAGCAGTCTAAGTGCCCGGACACTACCCCAAAACGGCGGCGCGCCTCGTCGCTGTC
	GCGTGACGCCGAGCGCCGAGCCTACCAATGGTGCCGGGAGTACTTGGGCGGGGCCTGGCGCCGAGTG
	CAGCCCGAGGAGCTGAGGGTTTACCCCGTGAGCGGAGGCCTCAGCAACCTGCTCTTCCGCTGCTCGC
	TCCCGGACCACCTGCCCAGCGTTGGCGAGGAGCCCCGGGAGGTGCTTCTGCGGCTGTACGGAGCCAT
	CTTGCAGGGCGTGGACTCCCTGGTGCTAGAAAGCGTGATGTTCGCCATACTTGCGGAGCGGTCGCTG
	GGGCCCCAGCTGTACGGAGTCTTCCCAGAGGGCCGGCTGGAACAGTACATCCCAAGTCGGCCATTGA
	AAACTCAAGAGCTTCGAGAGCCAGTGTTGTCAGCAGCCATTGCCACGAAGATGGCGCAATTTCATGG
	CATGGAGATGCCTTTCACCAAGGAGCCCCACTGGCTGTTTGGGACCATGGAGCGGTACCTAAAACAG
	ATCCAGGACCTGCCCCCAACTGGCCTCCCTGAGATGAACCTGCTGGAGATGTACAGCCTGAAGGATG
	ACATGGGCAACCTCAGGAAGTTACTAGAGTCTACCCCATCGCCAGTCGTCTTCTGCCACAATGACAT
	CCAGGAAGGGAACATCTTGCTGCTCTCAGAGCCAGAAAATGCTGACAGCCTCATGCTGCTGGACTTC
	GAGTACAGCAGTTATAACTATAGGGGCTTTGACATTGGGAACCATTTTTGTGAGPGGGTTTATGATT
	ATACTCACGAGGAATGGCCTTTCTACAAAGCAAGGCCCACAGACTACCCCACTCAAGAACAGCAGTT
	GCATTTTATTCGTCATTACCTGGCAGAGGCAAAGAAAGGTGAGACCCTCTCCCAAGAGGAGCAGAGA
	AAACTGGAAGAAGATTTGCTGGTAGAAGTCAGTCGGTATGCTCTGGCATCCCATTTCTTCTGGGGTC
	TGTGGTCCATCCTCCAGGCATCCATGTCCACCATAGAATTTGGTTACTTGGACTATGCCCAGTCTCG
	GTTCCAGTTCTACTTCCAGCAGAAGGGGCAGCTGACCAGTGTCCACTCCTCATCCTGACTCCACCCT
	CCCACTCCTTGGATTTCTCCTGGAGCCTCCAGGGCAGGACCTTGGAGGGAGGAACAACGAGCAGAAC
	GCCCTGGCGACTGGGCTGAGCCCCCAAGTGAAACTGAGGTTCAGGAGACCGGCCTGTTCCTGAGTTT
	GAGTAGGTCCCCATGGCTGGCACGCCAGAGCCCCGTGCTGTGTATGTAACACAATAAACAAGCTTC
	ORF Start: ATG at 144		ORF Stop: TGA at 1329
	SEQ ID NO:96	395 aa	MW at 45270.9 kD
NOV 17b,	MAAEATAVAGSGAVCGCLAKDGLQQSKCPDTTPKRRRASSLSRDAERRAYQWCREYLGGAURRVQPE
CG138563-02
Protein Sequence	ELRVYPVSGGLSNLLFRCSLPDHLPSVGEEPREVLLRLYGAILQGVDSLVLESVMFAILAERSLGPQ
	LYGVFPEGRLEQYIPSRPLKTQELREPVLSAAIATKMAQFHGMEMPFTKEPHWLFGTMERYLKQIQD
	LPPTGLPEMNLLEMYSLKDEMGNLRKLLESTPSPVVFCHNDIQEGNILLLSEPENADSLMLVDFEYS
	SYNYRGFDIGNHFCEWVYDYTHEEWPFYKARPTDYPTQEQQLHFIRHYLAEAKKGETLSQEEQRKLE
	EDLLVEVSRYALASHFFWGLWSILQASMSTIEFGYLDYAQSRFQFYFQQKGQLTSVHSSS

[0441] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 17B.

TABLE 17B
Comparison of NOV17a against NOV17b.
		NOV17a	Identities/
		Residues/	Similarities
	Protein	Match	for the
	Sequence	Residues	Matched Region
	NOV17b	58 . . . 317	236/266 (88%)
		20 . . . 282	241/266 (89%)

[0442] Further analysis of the NOV17a protein yielded the following properties shown in Table 17C.

TABLE 17C
Protein Sequence Properties NOV17a
PSort analysis: 0.9600 probability located in nucleus; 0.1629 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:

[0443] A search of the NOV17a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 17D.

TABLE 17D
Geneseq Results for NOV17a
		NOV17a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAY68787	Amino acid sequence of a	1 . . . 317	293/323 (90%)	e−166
	human phosphorylation	1 . . . 320	298/323 (91%)
	effector PHSP-19 - Homo
	sapiens, 433 aa.
	[WO200006728-A2,
	10 FEB. 2000]
AAU30777	Novel human secreted	7 . . . 329	258/335 (77%)	e−137
	protein #1268 - Homo	7 . . . 337	271/335 (80%)
	sapiens, 483 aa.
	[WO200179449-A2,
	25 OCT. 2001]
AAR32999	Rat choline kinase - Rattus	85 . . . 284	125/204 (61%)	5e−67
	rattus, 435 aa.	85 . . . 288	158/204 (77%)
	[JP05015367-A,
	26 JAN. 1993]
ABB58945	Drosophila melanogaster	123 . . . 284	67/174 (38%)	3e−32
	polypeptide SEQ ID NO	137 . . . 310	107/174 (60%)
	3627 - Drosophila
	melanogaster, 495 aa.
	[W0200171042-A2,
	27 SEP. 2001]
AAB87672	Bovine mammary tissue	188 . . . 247	55/60 (91%)	1e−26
	derived protein #63 - Bos	9 . . . 68	58/60 (96%)
	taurus, 69 aa.
	[WO200114553-A1,
	01 MAR. 2001]

[0444] 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 17E.

TABLE 17E
Public BLASTP Results for NOV17a
		NOV17a	Identities/
Protein		Residues/	Similarities
Accession		Match	for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
Q9Y259	Choline/ethanolamine kinase	39 . . . 317	255/285 (89%)	e−142
	[Includes: Choline kinase (EC	1 . . . 282	260/285 (90%)
	2.7.1.32) (CK); Ethanolamine
	kinase (EC 2.7.1.82)(EK)] - Homo
	sapiens (Human), 395 aa.
O55229	Choline/ethanolamine kinase	39 . . . 284	211/246 (85%)	e−122
	[Includes: Choline kinase (EC	1 . . . 246	226/246 (91%)
	2.7.1.32) (CK); Ethanolamine
	kinase (EC 2.7.1.82)(EK)] - Mus
	musculus (Mouse), 394 aa.
O54783	Choline/ethanolamine kinase	39 . . . 284	208/246 (84%)	e−120
	[Includes: Choline kinase (EC	1 . . . 246	226/246 (91%)
	2.7.1.32) (CK); Ethanolamine
	kinase (EC 2.7.1.82)(EK)] - Rattus
	norvegicus (Rat), 394 aa.
AAH36471	Similar to choline kinase - Homo	85 . . . 297	133/217 (61%)	7e−70
	sapiens (Human), 439 aa.	89 . . . 300	169/217 (77%)
P35790	Choline kinase (EC 2.7.1.32) (CK)	29 . . . 297	145/292 (49%)	2e−68
	(CHETK-alpha) - Homo sapiens	31 . . . 317	187/292 (63%)
	(Human), 456 aa.

[0445] PFam analysis predicts that the NOV17a protein contains the domains shown in the Table 17F.

TABLE 17F
Domain Analysis of NOV17a
		Identities/
	NOV17a	Similarities
	Match	for the	Expect
Pfam Domain	Region	Matched Region	Value
Choline_kinase	125 . . . 352	88/349 (25%)	1.6e−41
		192/349 (55%)

Example 18

[0446] 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:97	3705 bp
NOV18a,	CGGCTCGGGGCTGTGAGCGCCTCGGGGCCGGGGGTGGGCGGCGGTGCGGCGGGCGGCCGACGCTCCT
CG138848-01
DNA Sequence	CTTCGGCGGCCGCGGCGGCGGCCATGCGTGGGGCGGCGCGGCTGGCGCGGCCGGGCCGGAGTTGCCT
	CCCGGGGGCCCGCGGCCTGAGGGCCCCGCCGCCGCCGCCGCTGCTGCTTCTGCTTGCGCTGTTGCCG
	CTGCTGCCCGCGCCTGGCGCTGCCGCCGCCCCCGCCCCGCGGCCCCCGGAGCTGCAGTCGGCTTCCG
	CGGGGCCCAGCGTGAGTCTCTACCTGAGCGAGGACGAGGTGCGCCGGCTGATCGGTCTTGATGCAGA
	ACTTTATTATGTGAGAAATGACCTTATTAGTCACTACGCTCTATCCTTTAGTCTCTTAGTACCCAGT
	GAGACAAATTTCCTGCACTTCACCTGGCATGCGAAGTCCAAGGTTGAATATAAGCTGGGATTCCAAG
	TGGACAATGTTTTGGCAATGGATATGCCCCAGGTCAACATTTCTGTTCAGGCGGAAGTTCCACGCAC
	TTTATCAGTGTTTCGGGTAGAGCTTTCCTGTACTCGCAAAGTAGATTCTGAAGTTATGATACTAATG
	CAGCTCAACTTGACAGTAAATTCTTCAAAAAATTTTACCGTCTTAAATTTTAAACGAAGGAAAATGT
	GCTACAAAAAACTTGAAGAAGTAAAAACTTCAGCCTTGGACAAAAACACTAGCAGAACTATTTATGA
	TCCTGTACATGCAGCTCCAACCACTTCTACGCGTGTGTTTTATATTAGTGTAGGGGTTTGTTGTGCA
	GTAATATTTCTCGTAGCAATAATATTAGCTGTTTTGCACCTTCATAGTATGAAAAGGATTGAACTGG
	ATGACAGCATTAGTGCCAGCAGTAGTTCCCAAGGGCTGTCTCAGCCATCCACCCAGACGACTCAGTA
	TCTGAGAGCAGACACGCCCAACAAPGCAACTCCTATCACCAGCTCCTTAGGTTATCCTACCTTGCGG
	ATAGAGAAGAACGACTTGAGAAGTGTCACTCTTTTGGAGGCCAAAGGCAAGGTGAAGGATATAGCAA
	TATCCAGAGAGAGGATAACTCTAAAAGATGTACTCCAAGAAGGTACTTTTGGGCGTATTTTCCATGG
	GATTTTAATAGATGAAAAAGATCCAAATAAAGAAAAACAAGCATTTGTCAAAACAGTTAAAGATCAA
	GCTTCTGAAATTCAGGTGACAATGATGCTCACTGAAAGTTGTAAGCTGCGAGGTCTTCATCACAGAA
	ATCTTCTTCCTATTACTCATGTGTGTATAGAAGAAGGAGAAAAGCCCATGGTGATATTGCCTTACAT
	GAATTGGGGGAATCTTAAATTGTTTTTACGACAGTGCAAGTTAGTAGAGGCCAATAATCCACAGGCA
	ATTTCTCAGCAAGACCTGGTACACATGGCTATTCAGATTGCCTGTGGAATGAGCTACCTGGCCAGAA
	GGGAAGTCATCCACAAAGACCTGGCTGCCAGGAACTGTGTCATTGATGACACACTTCAAGTTAAGAT
	CACAGACAATGCCCTCTCCAGAGACTTGTTCCCCATGGACTATCACTGTCTGGGGGACAATGAAAAC
	ACGCCAGTTCGTTGGATGGCTCTTGAAAGTCTGGTTAATAACGAGTTCTCTAGCGCTAGTGATGTGT
	GGGCCTTTGGAGTGACGCTGTGGGAACTCATGACTCTGGGCCAGACTCCCTACGTGGACATTGACCC
	CTTCGAGATGGCCGCATACCTGAAAGATGGTTACCGAATAGCCCAGCCAATCAACTGTCCTGATGAA
	TTATTTGCTGTGATGGCCTGTTGCTGGGCCTTAGATCCAGAGGAGAGGCCCAAGTTTCAGCAGCTGG
	TACAGTGCCTAACAGAGTTTCATGCACCCCTCGGGGCCTACGTCTGACTCCTCTCCAATCCCACACC
	ATCAGGAAGAAGGTGCCTGTCGGGGCTCACTTGAAGCCTGTCAGGGATGCTTTGTATCTAACACAAC
	GCCAACAGAAGCACATTTGTCTTCCAGAACACCGTGCCTTAGAAATGCTTTAGAATCTGAACTTTTT
	AAGACAGACTTAATAATGTGGCATATTTTCTAGATATCACTTTTATTAGGTTGAACTGAAAGGGTTT
	TTGTAAATTTTTTGGCCAAAATTTTTTAAAACATACTTACTTTGGACTAGGGGTACATTCTTACAAA
	ATAAATAAACAGTTTTTAAAATTGTTTAGACACAGATATTTGGAATTAGCTATCTTAGTGCCAACTG
	CTTTTTATTTTTTTACTTCATCAAGGTGATGTAAGTGACTCACCTTTAAAGTTTTTTTAGTGTTATT
	TTTTATCACTACTCTGGGAAATGGTTTGTCTTCAAGATGCAATACTTTTCTTAGTAAAGGAAAAACA
	GCATAAAAAGATACCTGGTCTGCCTTGTACAAGAAAAGGCAATATTAGAGGAAGAAAATTTAAAGAA
	AAGCTAGAGGAAAAAAAAATTTTTTTAAAAATACTTATTAGAAGCAAACTGCCCTTGCATGGAAAAC
	TGTTTATTTTTTTCAGTGAAAAGGAATTCTGCTTTCGTGTTTTTGGGAAAGCAGGAACTGAGTTCAT
	TACATCTTTAATTTGGCAGAAATTAGCCTTTCTGTGAACCAGATGTGGTTTGGGGCAGATCTGTTGT
	AAACAATGGTGATTTTATTTATTTTTACTCTCTGGAAAAGGAGATAATACAATTCCAGAAAGTGAAC
	TCATATTTCTAAGGTTAAGATTCCCTTTTATTGCACCTAGAATAGTGCTATGCACAGAGCGGGTGCT
	TGAGTTGTTGTCGTTTTTTGTTTGTTTTTTAAATGTAAACTGGTAAATTTTGTGCTTATCTTCAAGG
	CTGGCTTAAGTATAAAATTGTTTTTTAAACACTTGAAAAATTAAAGGATTTGTTTTATATTATGACA
	GTATTGAAATTATTTTTCATAATGAATGATTGGTTATTGTGTCTGGTAAGTCTTTGAACATTCAACA
	GCCAGACATTTGTGTTTTATTTCATGATGTTCCAGTCAAGTTCCAAAGCCCTAACACAGTTAAACTG
	GCTCAGACTCCAGGTTCTAGTAAAAAGTTGGAATTAATGTTATAAGGAAGTATTAAAACACTGAAAC
	ATTTCTCCAGAACCAGCAAGTAAGGGATATGTATGTATTTATGCTCAGTTTTAGTTGGCCTAAAGCA
	GAGTTGAATGGGCTTTCTAAATAGCTAGCCCTGCAGGTACCTGCCACTACTCCCATCTTCAGAGGTA
	TATAAGGGAGAATGTGTAGCAGTTTGACGCTTTTGCTGTTTTTAAAAAAGCCTTATGAATCAGCAGC
	ACACCGGGAAAAATAGCTCACATAGTACCTGGTTTTCCACAAGTAAGCCAAGGGCATGATTTTCTGT
	GTACATTTATTAACAGTTCTTTGGTTTTATGAAATACTCATATGAAGCCAGTCCCTGGAGTACTGTT
	TTTTAAAAGGTCCCTTTGAACCATTTGTAAATTATATTTTCATTCATAACCTGCATTCTTAGAAGGC
	ATTCAGTCAACATTTACAGCACTTACTGTGTATTTTCCACATGGAGTGGTTCAACTCAAGCGTCCCT
	TCCAGTATTCAGGGCATTCTTATTTCATGTTCAAGTGAGTGCATTGTTTAGAAATCACAGTTTATTA
	ACATGTACATGATCTATTTT
	ORF Start: ATG at 91		ORF Stop: TGA at 1921
	SEQ ID NO:98	610 aa	MW at 68071.0 kD
NOV18a,	MRGAARLGRPGRSCLPGARGLRAPPPPPLLLLLALLPLLPAPGAAAAPAPRPPELQSASAGPSVSLY
CG138848-011
Protein Sequence	LSEDEVRRLIGLDAELYYVRNDLISHYALSFSLLVPSETNFLHFTWHAXSKVEYKLGFQVDNVLAMD
	MPQVNTSVQGEVPRTLSVFRVELSCTGKVDSEVMILMQLNLTVNSSKNFTVLNFKRRKMCYKKLEEV
	KTSALDKNTSRTIYDPVHAAPTTSTRVFYISVGVCCAVIFLVAITLAVLHLHSMKRIELDDSISASS
	SSQGLSQPSTQTTQYLRADTPNNATPITSSLGYPTLRIEKNDLRSVTLLEAKGKVKDIAISRERITL
	KDVLQEGTFGRIFHGILIDEKDPNKEKQAFVKTVKDQASEIQVTMMLTESCKLRGLHHRNLLPITHV
	CIEEGEKPMVILPYMNWGNLKLFLRQCKLVEANNPQAISQQDLVHMAIQIACGMSYLARREVIHKDL
	AARNCVIDDTLQVKITDNALSRDLFPMDYHCLGDNENRPVRWMALESLVNNEFSSASDVWAFGVTLW
	ELMTLGQTPYVDIDPFEMAAYLKDGYRIAQPINCPDELFAVMACCWALDPEERPKFQQLVQCLTEFH
	AALGAYV

[0447] Further analysis of the NOV18a protein yielded the following properties shown in Table 18B.

TABLE 18B
Protein Sequence Properties NOV18a
PSort     0.6000 probability located in plasma membrane;
analysis: 0.4000 probability located in Golgi body; 0.3000
          probability located in endoplasmic reticulum
          (membrane); 0.3000 probability located in
          microbody (peroxisome)
SignalP   Cleavage site between residues 47 and 48
analysis:

[0448] 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
Geneseq	Protein/Organism/Length	Match	for the	Expect
Identifier	[Patent #, Date]	Residues	Matched Region	Value
AAG66030	Amino acid sequence of seq	1 . . . 610	604/610 (99%)	0.0
	Id No. 6 - Homo sapiens, 607	1 . . . 607	606/610 (99%)
	aa. [WO200185789-A2,
	15 NOV. 2001]
AAR42480	Human RYK cDNA - Homo	1 . . . 610	581/612 (94%)	0.0
	sapiens, 606 aa.	1 . . . 606	587/612 (94%)
	[WO9323429-A,
	25 NOV. 1993]
AAR42479	Mouse RYK - Mus musculus,	46 . . . 610	539/565 (95%)	0.0
	593 aa. [WO9323429-A,	32 . . . 593	548/565 (96%)
	25 NOV. 1993]
ABB57333	Mouse ischaemic condition	9 . . . 331	291/323 (90%)	e−158
	related protein sequence SEQ	2 . . . 314	298/323 (92%)
	ID NO: 928 - Mus musculus,
	317 aa. [WO200188188-A2,
	22 NOV. 2001]
AAG66025	Ryk protein extracellular	47 . . . 237	190/191 (99%)	e−105
	domain - Homo sapiens, 191	1 . . . 191	191/191 (99%)
	aa. [WO200185789-A2,
	15 NOV. 2001]

[0449] 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
Accession		Match	for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
I37560	protein-tyrosine kinase (EC	1 . . . 610	603/610 (98%)	0.0
	2.7.1.112) ryk - human, 607	1 . . . 607	605/610 (98%)
	aa.
P34925	Tyrosine-protein kinase RYK	1 . . . 610	585/610 (95%)	0.0
	precursor (EC 2.7.1.112) -	1 . . . 604	588/610 (95%)
	Homo sapiens (Human), 604
	aa.
Q01887	Tyrosine-protein kinase RYK	9 . . . 610	566/602 (94%)	0.0
	precursor (EC 2.7.1.112)	2 . . . 594	577/602 (95%)
	(Kinase VIK) (NYK-R)
	(Met-related kinase) - Mus
	musculus (Mouse), 594 aa.
I58386	receptor tyrosine kinase -	9 . . . 610	565/602 (93%)	0.0
	mouse, 594 aa.	2 . . . 594	576/602 (94%)
A47186	receptor protein tyrosine	9 . . . 610	550/602 (91%)	0.0
	kinase homolog RYK - mouse,	2 . . . 593	562/602 (92%)
	593 aa.

[0450] PFam analysis predicts that the NOV18a protein contains the domains shown in the Table 18E.

TABLE 18E
Domain Analysis of NOV18a
		Identities/
	NOV18a	Similarities
	Match	for the	Expect
Pfam Domain	Region	Matched Region	Value
WIF	66 . . . 194	64/147 (44%)	1.7e−69
		125/147 (85%)
pkinase	333 . . . 599	78/302 (26%)	1.8e−76
		216/302 (72%)

Example 19

[0451] 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:99	1983bp
NOV 19a,	GGTAGAGCGGAGACGACGCTCCCAGACTCCTCCGGTCTCCCCGGGCAGCATGAAGACCGCCGAGAAC
CG139990-01
DNA Sequence	ATCAGAGGAACCCGCAGCGACGGGCCGCGGAAACGAGGCCTCTGCGTCCTCTGTGGCCTCCCCGCGG
	CAGGAAAATCGACTTTCGCGCGCGCCCTCGCCCACCGOCTGCAGCAGGAGCAGGGTTGGGCCATCGG
	TGTTGTCGCGTATGATGACGTCATGCCCGACGCGTTTCTCGCCGGGGCAAGAGCGCGACCGGCGCCA
	TCCCAATGGAAATTGCTTCGACAGGAACTGTTGAAGTACCTGGAATACTTCTTGATGGCTGTCATTA
	ATGGGTGTCAGATGTCTGTCCCACCCAACAGGACTGAAGCCATGTGGGAAGATTTTATAACCTGCTT
	AAAGGATCAAGATCTGATATTTTCTGCAGCATTTGAGGCCCAGTCTTGCTACCTCTTAACAAAAACT
	GCTGTTTCTAGACCTTTGTTTTTGGTTTTGGATGACAATTTTTATTATCAGAGTATGAGATATGAAG
	TCTACCAGCTGGCTCGGAAATATTCATTGGGCTTTTGCCAGCTCTTTTTAGATTGTCCTCTTGAGAC
	CTGTTTACAGACGAATGGCCAGAGGCCACAGGCACTGCCTCCTGAGACCATCCACCTGATGCGAAGA
	AAGCTAGAAAAGCCCAACCCTGAGAAAAATGCTTGGGAACACAACAGCCTCACAATTCCGAGTCCAG
	CATGTGCTTCGGAGGCCAGATGAACAAGTGCTTCCTCACAACTTGAAGCTTCTAGCAGAAGAACTTA
	ACCAGCTCAAAGCAGAGTTTTTGOAAGACCTAAAACAAGGAAACAAAAAATATCTGTGCTTTCAGCA
	AACCATTGACATACCAGATGTCATTTCTTTTTTTCATTATGAGAAAGATAATAPTGTACAGAAGTAT
	TTTTCAAAGCAGCATTAAAATTTCTGAACTGCCAAAAAAAAAAAA
	ORF Start: ATG at 50		ORF Stop: TGA at 758
	SEQ ID NO:100	1236 aa	MW at 26728.5 kD
NOV19a,	MKTAENIRGTGSDGPRKRGLCVLCGLPAAGKSTFARALAHRLQQEQGWAIGVVAYDDVMPDAFLAGA
CG139990-01
Protein Sequence	RARPAPSQWKLLRQELLKYLEYFLMAVINGCQNSVPPNRTEAMWEDFITCLKDQDLIFSAAFEAQSC
	YLLTKTAVSRPLFLVLDDNFYYQSMRYEVYQLARKYSLGFCQLFLDCPLETCLQRNGQRPQALPPET
		IHLMRRKLEKPNPEKNAWEHNSLTIPSPACASEAR

[0452] Further analysis of the NOV19a protein yielded the following properties shown in Table 19B.

TABLE 19B
Protein Sequence Properties NOV19a
PSort     0.3700 probability located in outside; 0.1000
analysis: probability located in endoplasmic reticulum
          (membrane); 0.1000 probability located in
          endoplasmic reticulum (lumen); 0.1000
          probability located in lysosome (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0453] 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
		Residues/	Identities/
Geneseq	Protein/Organism/Length	Match	Similarities for the	Expect
Identifier	[Patent #, Date]	Residues	Matched Region	Value
AAB73511	Human transferase HTFS-18,	1 . . . 235	235/235 (100%)	e−138
	SEQ ID NO: 18 - Homo	1 . . . 235	235/235 (100%)
	sapiens, 358 aa.
	[WO200132888-A2,
	10 MAY 2001]
AAB47957	Homo zinc finger protein	95 . . . 220	123/126 (97%)	1e−69
	18.04 - Homo sapiens, 164	21 . . . 146	124/126 (97%)
	aa. [WO200220595-A1,
	14 MAR. 2002]
AAU14714	Novel bone marrow	121 . . . 235	115/115 (100%)	7e−64
	polypeptide #113 - Homo	1 . . . 115	115/115 (100%)
	sapiens, 238 aa.
	[WO200157187-A2,
	9 AUG. 2001]
AAG74560	Human colon cancer antigen	21 . . . 107	86/87 (98%)	1e−44
	protein SEQ ID NO: 5324 -	12 . . . 98	86/87 (98%)
	Homo sapiens, 98 aa.
	[WO200122920-A2,
	5 APR. 2001]
ABB65970	Drosophila melanogaster	16 . . . 226	62/216 (28%)	2e−12
	polypeptide SEQ ID NO	2 . . . 178	94/216 (42%)
	24702 - Drosophila
	melanogaster, 292 aa.
	[WO200171042-A2,
	27 SEP. 2001]

[0454] 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
Q9VWF7	CG12788 protein (SD05444P) -	16 . . . 226	62/216 (28%)	5e−12
	Drosophila melanogaster	2 . . . 178	94/216 (42%)
	(Fruit fly), 292 aa.
Q8TUS5	Predicted nucletide kinase -	20 . . . 234	57/219 (26%)	6e−08
	Methanopyrus kandleri, 255	3 . . . 160	90/219 (41%)
	aa.
Q58933	Hypothetical protein MJ1538 -	129 . . . 226	30/98 (30%)	4e−07
	Methanococcus jannaschii,	57 . . . 152	55/98 (55%)
	252 aa.
Q9XTU1	Y49E10.22 protein -	134 . . . 213	24/82 (29%)	0.015
	Caenorhabditis elegans, 259	58 . . . 139	44/82 (53%)
	aa.
P34253	KTI12 protein -	139 . . . 229	24/92 (26%)	0.015
	Saccharomyces cerevisiae	73 . . . 163	44/92 (47%)
	(Baker's yeast), 313 aa.

[0455] PFam analysis predicts that the NOV19a protein contains the domains shown in the Table 19E.

TABLE 19E
Domain Analysis of NOV19a
		Identities/
	NOV19a	Similarities
Pfam	Match	for the Matched	Expect
Domain	Region	Region	Value
No Significant Matches Found to Publically Available Domains

Example 20

[0456] 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:101	3875 bp
NOV2Oa,	CGGGGGACGTCAGCGCTGCCAGCGTGGAAGGAGCTGCGGGGCGCGGGAGGAGGAAGTAGAGCCCCGC
CG140041-01
DNA Sequence	ACCGCCAGGCCACCACCGGCCGCCTCAGCCATGGACGCGTCCCTGGAGAAGATAGCAGACCCCACGT
	TAGCTGAAATGGGAAAAAACTTGAAGGAGGCAGTGAAGATGCTGGAGGACAGTCAGAGAAGAACAGA
	AGAGGAAAATGGAAAGAAGCTCATATCCGGAGATATTCCAGGCCCACTCCAGGGCAGTGGGCAAGAT
	ATGGTGAGCATCCTCCAGTTAGTTCAGAATCTCATGCATGGAGATGAAGATGAGGAGCCCCAGAGCC
	CCAGAATCCAAAATATTGGAGAACAAGGTCATATGGCTTTGTTGGGACATAGTCTCGGAGCTTATAT
	TTCAACTCTGGACAAAGAGAAGCTGAGAAAACTTACAACTAGGATACTTTCAGATACCACCTTATGG
	CTATGCAGAATTTTCAGATATGAAAATGGGTGTGCTTATTTCCACGAAGAGGAAAGAGAAGGACTTG
	CAAAGATATGTAGGCTTGCCATTCATTCTCGATATGAAGACTTCGTAGTGGATGGCTTCAATGTGTT
	ATATAACAAGAAGCCTGTCATATATCTTAGTGCTGCTGCTAGACCTGGCCTGGGCCAATACCTTTGT
	AATCAGCTCGGCTTGCCCTTCCCCTGCTTGTGCCGTGTACCCTGTAACACTGTGTTTGGATCCCAGC
	ATCAGATGGATGTTGCCTTCCTGGAGAAACTGATTAAAGATGATATAGAGCGAGGAAGACTGCCCCT
	GTTGCTTGTCGCAAATGCAGGAACGGCAGCAGTAGGACACACAGACAAGATTGGGAGATTGAAAGAA
	CTCTGTGAGCAGTATGGCATATGGCTTCATGTGGAGGGTGTGAATCTGGCAACATTGGCTCTGGGTT
	ATGTCTCCTCATCAGTGCTGGCTGCAGCCAAATGTGATAGCATGACGATGACTCCTGGCCCGTGGCT
	GGGTTTGCCAGCTGTTCCTGCGGTGACACTGTATAAACACGATGACCCTGCCTTGACTTTAGTTGCT
	GGTCTTACATCAAATAAGCCCACAGACAAACTCCGTGCCCTGCCTCTGTGGTTATCTTTACAATACT
	TGGGACTTGATGGGTTTGTGGAGAGGATCAAGCATGCCTGTCAACTGAGTCAACGGTTGCAGGAAAG
	TTTGAAGAAAGTGAATTACATCAAAATCTTGGTGGAAGATGAGCTCAGCTCCCCAGTGGTGGTGTTC
	AGATTTTTCCAGGAATTACCAGGCTCAGATCCGGTGTTTAAAGCCGTCCCAGTGCCCAACATGACAC
	CTTCAGGAGTCGGCCGGGAGAGGCACTCGTGTGACGCGCTGAATCGCTGGCTGGGAGAACAGCTGAA
	GCAGCTGGTGCCTGCAAGCGGCCTCACAGTCATGGATCTGGAAGCTGAGGGCACGTGTTTGCGGTTC
	AGCCCTTTGATGACCGCAGCAGTTTTAGGAACTCGGCGAGAGGATGTGGATCAGCTCGTAGCCTGCA
	TAGAAAGCAAACTGCCAGTGCTGTGCTGTACGCTCCAGTTGCGTGAAGAGTTCAAGCAGGAAGTGGA
	AGCAACAGCAGGTCTCCTATATGTTGATGACCCTAACTGGTCTGGAATAGGGGTTGTCAGGTATGAA
	CATGCTAATGATGATAAGAGCAGTTTGAAATCAGATCCCGAAGGGGAAAACATCCATGCTGGACTCC
	TGAAGAAGTTAAATGAACTGGAATCTGACCTAACCTTTAAAATAGGCCCTGAGTATAAGAGCATGAA
	GAGCTGCCTTTATGTCGGCATCGCGAGCGACAACGTCGATGCTGCTGAGCTCGTGGAGACCATTGCG
	GCCACAGCCCGGGAGATAGAGGAGAACTCGAGGCTTCTGGAAAACATGACAGAAGTGGTTCGGAAAG
	GCATTCAGGAAGCTCAAGTGGAGCTGCAGAAGGCAAGTGAAGAACGGCTTCTGGAAGAGGGGGTGTT
	GCGGCAGATCCCTGTAGTGGGCTCCGTGCTGAATTCGTTTTCTCCGGTCCAGGCTTTACAGAAGGGA
	AGAACTTTTAACTTGACAGCAGGCTCTCTGGAGTCCACAGAACCCATATATGTCTACAAAGCACAAG
	GTGCAGGAGTCACGCTGCCTCCAACGCCCTCCGGCAGTCGCACCAAGCAGAGGCTTCCAGGCCAGAA
	GCCTTTTAAAAGGTCCCTGCGAGGTTCAGATGCTTTGAGTGAGACCAGCTCAGTCAGTCACATTGAA
	GACTTAGAAAAGGTGGAGCGCCTATCCAGTGCGCCGGAGCAGATCACCCTCOAGGCCAGCAGCACTG
	AGGGACACCCAGGGGCTCCCAGCCCTCAGCACACCGACCAGACCGAGGCCTTCCAGAAAGGGGTCCC
	ACACCCAGAAGATGACCACTCACAGGTAGAAGGACCGGAGAGCTTAAGATGAGACTCATTGTGTGGT
	TTGAGACTGTACTGAGTATTGTTTCAGGGAAGATGAAGTTCTATTGGAAATGTGAACTGTGCCACAT
	ACTAATATAAATTACTGTTGTTTGTGCTTCACTGGGATTTTGGCACAAATATGTGCCTGAAAGGTAC
	GCTTTCTAGGAGGGGAGTCAGCTTGTCTAACTTCATGTACATGTAGAACCACGTTTGCTGTCCTACT
	ACGACTTTTCCCTAAGTTACCATAAACACATTTTATTCACAAAAAACACTTCGAATTTCAAGTGTCT
	ACCAGTAGCACCCTTGCTCTTTCTAAACATAAGCCTAAGTATATGAGGTTGCCCGTGGCAACTTTTT
	GGTAAAACAGCTTTTCATTAGCACTCTCCAGGTTCTCTGCAACACTTCACAGAGGCGAGACTGGCTG
	TATCCTTTGCTGTCGGTCTTTAGTACGATCAAGTTGCAATATACAGTGGGACTGCTAGACTTGAAGG
	AGAGCAGTGATTGTGGGATTGTAAATAAGAGCATCAGAAGCCCTCCCCAGCTACTGCTCTTCGTGGA
	GACTTAGTAAGGACTGTGTCTACTTGAGCTGTGGCAAGGCTGCTGTCTGGGACTGTCCTCTGCCACA
	AGGCCATTTCTCCCATTATATACCGTTTGTAAAGAGAAACTGTAAAGTCTCCTCCTGACCATATATT
	TTTAAATACTGGCAAAGCTTTTAAAATTGGCACACAAGTACAGACTGTGCTCATTTCTGTTTAGTAT
	CTGAAAACCTGATAGATGCTACCCTPAAGAGCTTGCTCTTCCGTGTGCTACGTAGCACCCACCTGGT
	TAAAATCTGAAAACAAGTACCCCTTTGACCTGTCTCCCACTGAAGCTTCTACTGCCCTGGCAGCTCC
	CCTGGGCCCAACTCAGAAACAGGAGCCAGCAGAGCACTCTCTCACGCTGATCCAGCCGGGCACCCTC
	CTTAAGTCAGTAGAAGCTCGCTGGCACTGCCCGTTCCTACTTTTCCGAAGTACTGCGTCACTTTGTC
	GTAAGTAATGGCCCCTGTGCCTTCTTAATCCAGCAGTCAAGCTTTTGGGAGACCTGAAAATGGGAAA
	ATTCACACTGGGTTTCTGGACTGTAGTATTGGAAGCCTTAGTTATAGTATATTAAGCCTATAATTAT
	ACTCTGATTTGATGGGATTTTTGACATTTACACTTCTCAAAATGCAGGGGGTTTTTTTTCGTGCAGA
	TGATTAAACAGTCTTCCCTATTTGGTGCAATCAAGTATAGCAGATAAAATGGGGGAGGGGTAAATTA
	TCACCTTCAAGAAAATTACATGTTTTTATATATATTTGGAATTGTTAAATTGGTTTTGCTGAAACAT
	TTCACCCTTGAGATATTATTTGAATGTTGCTTTCAATAAAGGTTCTTGAAATTGTT
	ORE Start: ATG at 98		ORF Stop: TGA at 2462
	SEQ ID NO:102	788 aa	MW at 86705.9 kD
NOV2Oa,	MDASLEKIADPTLAEMGKNLKEAVKMLEDSQRRTEEENGKKLISGDIPGPLQGSGQDMVSILQLVQN
CG14004101
Protein Sequence	LMHGDEDEEPQSPRIQNIGEQGHIMLLGHSLGAYISTLDKEKLRKLTTRILSDTTLWLCRIFRYENG
	CAYFHEEEREGLAKICRLAIHSRYEDFVVDGFNVLYNXKPVIYLSAAARPGLGQYLCNQLGLPFPCL
	CRVPCNTVFGSOHQMDVAFLEKLIKDDIERGRLPLLLVANAGTAAVGHTDKIGRLKELCEOYGIWLH
	VEGVNLATLALGYVSSSVLAAAKCDSMTMTPGPWLGLPAVPAVTLYKHDDPALTLVAGLTSNKPTDK
	LRALPLWLSLQYLGLDGFVERIKHACQLSQRLQESLKKVNYIKILVEDELSSPVVVFRFFQELPGSD
	PVFKAVPVPNMTPSGVGRERHSCDALNRWLGEQLKQLVPASGLTVMDLEAEGTCLRFSPLMTAAVLG
	TRGEDVDQLVACIESKLPVLCCTLQLREEFKQEVEATAGLLYVDDPNWSGIGVVRYEHANDDKSSLK
	SDPEGENIHAGLLKKLNELESDLTFKIGPEYKSMKSCLYVGMASDNVDAAELVETIAATAREIEENS
	RLLENMTEVVRKGIQEAQVELQKASEERLLEEGVLRQIPVVGSVLNWFSPVQALQKGRTFNLTAGSL
	ESTEPIYVYKAQGAGVTLFPTPSGSRTKQRLPGQKPFKRSLRGSDALSETSSVSHIEDLEKVERLSS
	GPEQITLEASSTEGHPGAPSPQHTDQTEAFQKGVPHPEDDHSQVEGPESLR

[0457] 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; 0.3000
analysis: 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:

[0458] 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
		Residues/	Identities/
Geneseq	Protcin/Organism/Length	Match	Similarities for the	Expect
Identifier	[Patent #, Date]	Residues	Matched Region	Value
AAM39095	Human polypeptide SEQ ID	1 . . . 788	788/788 (100%)	0.0
	NO 2240 - Homo sapiens,	1 . . . 788	788/788 (100%)
	788 aa. [WO200153312-A1,
	26 JUL. 2001]
AAM40881	Human polypeptide SEQ ID	1 . . . 788	784/788 (99%)	0.0
	NO 5812 - Homo sapiens,	33 . . . 820	786/788 (99%)
	820 aa. [WO200153312-A1,
	26 JUL. 2001]
AAM25938	Human protein sequence	1 . . . 466	466/466 (100%)	0.0
	SEQ ID NO: 1453 - Homo	36 . . . 501	466/466 (100%)
	sapiens, 518 aa.
	[WO200153455-A2,
	26 JUL. 2001]
AAG75454	Human colon cancer antigen	381 . . . 788	408/408 (100%)	0.0
	protein SEQ ID NO: 6218 -	18 . . . 425	408/408 (100%)
	Homo sapiens, 425 aa.
	[WO200122920-A2,
	5 APR. 2001]
AAB57103	Human prostate cancer	432 . . . 788	357/357 (100%)	0.0
	antigen protein sequence	15 . . . 371	357/357 (100%)
	SEQ ID NO: 1681 - Homo
	sapiens, 371 aa.
	[WO200055174-A1,
	21 SEP. 2000]

[0459] 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
		NOV20a
Protein		Residues/	Identities/
Accession		Match	Similarities for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
O00236	KIAA0251 protein - Homo	1 . . . 788	788/788 (100%)	0.0
	sapiens (Human), 820 aa	33 . . . 820	788/788 (100%)
	(fragment).
Q99K01	Hypothetical 87.3 kDa	1 . . . 788	697/788 (88%)	0.0
	protein - Mus musculus	1 . . . 787	726/788 (91%)
	(Mouse), 787 aa.
Q9DC25	Adult male lung cDNA,	1 . . . 702	638/702 (90%)	0.0
	RIKEN full-length enriched	1 . . . 702	664/702 (93%)
	library, clone: 1200006G13,
	full insert sequence - Mus
	musculus (Mouse), 710 aa.
Q8TBS5	Similar to KIAA0251	193 . . . 788	595/596 (99%)	0.0
	hypothetical protein - Homo	3 . . . 598	596/596 (99%)
	sapiens (Human), 598 aa
	(fragment).
AAH33748	Similar to expressed	1 . . . 369	345/369 (93%)	0.0
	sequence AA415817 - Homo	1 . . . 346	346/369 (93%)
	sapiens (Human), 347 aa.

[0460] PFam analysis predicts that the NOV20a protein contains the domains shown in the Table 20E.

TABLE 20E
Domain Analysis of NOV20a
			Identities/
		NOV20a	Similarities
		Match	for the Matched	Expect
	Pfam Domain	Region	Region	Value
	pyridoxal_deC	214 . . . 269	22/62 (35%)	1.6e−12
			44/62 (71%)

Example 21

[0461] 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:103	1683 bp
NOV21a,	TTATGTCGGGTCGCGGGGTGTCATGACAGCATGGCAGACTACCTGATCAGCAGCGGCACCAGCTACG
CG14006101
DNA Sequence	TGCCCGAGGACGGGCTCACCGCGCAGCAGCTCTTCACCAGCACCAACGGCCTCACCTACAATGACTT
	CCTGATTCTCCCAOGATTCATAGACTTCATAGCTGATGATGAGGTGGACCTCACCTCAGCCCTGACC
	CACAAGGGCCTGAAGACGCCGCTGATCTCCTCCCCTATGGACACTTCTCCTCCCCTGTGGACACTGA
	CAGAGGCTGACATGGCAATCGGGATGGCTCTGATGGGAGGTATTGGTTTCATTCACCACAACTGCAC
	CCCAGAGTTCGAGGCCAATGAGGTGCTGAAGGTCAAGAAGTTTGAACAGGGCTTCATCACGGACCCT
	GTGGTGCTGAGCCCCTTGCACACCGTGGGTGATGTGCTTCTGAAGACGCCGCTGATCTCCTCCCCTG
	TGGACACTGAGGCCAAGATGCTGCATCGCTTCTCTGGTATCCCCCTCACTGAGACGGGCACCATGGG
	CAGCAAGCTGGTGGGCATCATCACCTCCCGAGACGTCGACTTTCTTGCTAAGAAGGAGCACGCCACC
	TTCATCAGTGAGGTGATGACCCCAAGCATGGAACTGGTGGTGGCTGACAAAGGTGTGACGTTGAAAG
	AGGCAAATGAGATCCTGCAGCGTAACAAGAAAGGGAAGCTGCCTATCGTCAGTGATCGCGATGAGCT
	GGTGGCCATCATTGCCCGCACTGACCTGAAGAAGAATCGAGACTACCCTCTGGCCTCCAAGGATTCC
	CACAAACAGCTGCTGTGCAGGGCAGCTGTGGGCACCCGTGAGGATGACGAATGCCACCTGGACCTGC
	TCACCCAGGCGGGTGTCAATGTTGTAGTCTTGGACTCATCCCAAGGGAGCTCGGTGTATCAGATCAC
	CATGGTGCATTACATCAAACAGAAGTACCCCCACCTCCAGGTGATTGGGGGGAACGTGGTGACAGCA
	GCCCAGGCCAAGAACCTGATGGACGCTCGTGTGGACGGGCTGCATGTGGGCATGGGCTACGGCTCCA
	TCTGCATTACCCAGAAAGTGATGGCCTGCGGTTGGCCCCAGGGCACTGCTGTGTACAAGGTCGCCAA
	GTATGCCCAGTGCTTTGGTGTGCCCATCATAGTCGATGGTGGCATCCAGACTGTGGGGCACGTGGTC
	AAGGCCCTGGCCCTTGGAGCCTCCACAGTGATGATGGCCTCCCTGCTGGCCACCACCACGGAGGCAC
	CTGGTGAGTACTTCTTCTTAGAAAGGGTGCAGCTCAAGAAGTACCAGGGCATGGGCTCACTGGATGC
	CATGGAGAAGAGCAGCAGCAGCCAGAAACGATACTTCAGCAAGCGGGATAAGGTGAAGATCGCACAG
	GGTGTCTCGGGCTCCATCCAGGACAAAGGGTCCATTCAGAAGTTCGTGCCCTACCTCATAGCGGGCA
	TCCAGCACAGCTGCCAGGATATCGGGGCCCGCAGCCTGTCTGTCCTTTGGTCCATGATGTACTCAGG
	GGAGCTCAAGTTTGAGAAGCAGACCATGTCGGCCCAGATCAAGGGTGGTGTCCATGGCCTGCACTCG
	TATGAGAAGCAGCTGTGATGAGGACAGCGGTGGAGGCTCAGGTCGTGCAGCGGGTGCACCCTGAAGA
	CGCCGCTG
	ORF Start: ATG at 31		ORE Stop: TGA at 1624
	SEQ ID NO:104	531 aa	MW at 57605.0 kD
NOV21a,	MADYLISSGTSYVPEDGLTAQQLFTSTNGLTYNDFLILPGFIDFIADDEVDLTSALTHKGLKTPLIS
CG140061-01
Protein Sequence	SPMDTSPPLWTLTEADMAIGMALMGGIGFIHHNCTPEFEANEVLKVKKFEQGFITDPVVLSPLHTVG
	DVLLKTPLISSPVDTEAKMLHGFSGIPLTETGTMGSKLVGIITSRDVDFLAKKEHATFISEVMTPRM
	ELVVADKGVTLKEANEILQRNKKGKLPIVSDRDELVAIIARTDLKKNRDYPLASKDSHKQLLCRAAV
	GTREDDECHLDLLTQAGVNVVVLDSSQGSSVYQITMVHYIKQKYPHLQVIGGNVVTAAQAKNLMDAR
	VDGLHVGMGYGSICITQKVMACGWPQGTAVYKVAKYAQCFGVPIIVDGGIQTVGHVVKALALGASTV
	MMGSLLATTTEAPGEYFFLERVQLKKYQGMGSLDAMEKSSSSQKRYFSKGDKVKIAQGVSCSIQDKG
	SIQKFVPYLIAGIQHSCQDIGARSLSVLWSMMYSGELKFEKQTMSAQIKGGVHGLHSYEKQL

[0462] Further analysis of the NOV21a protein yielded the following properties shown in Table 21B.

TABLE 21B
Protein Sequence Properties NOV21a
PSort     0.4500 probability located in cytoplasm;
analysis: 0.3785 probability located in microbody
          (peroxisome); 0.1507 probability located
          in lysosome (lumen); 0.1000 probability
          located in mitochondrial matrix space
SignalP   No Known Signal Sequence Predicted
analysis:

[0463] A search of the NOV21 a 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
AAE18188	Human wild-type inosine	1 . . . 531	454/532 (85%)	0.0
	5′-monophosphate	1 . . . 513	481/532 (90%)
	dehydrogenase (IMPDH) -
	Homo sapiens, 514 aa.
	[WO200185952-A2,
	15 NOV. 2001]
AAE18257	Human type I inosine	1 . . . 531	453/532 (85%)	0.0
	5′-monophosphate	1 . . . 513	480/532 (90%)
	dehydrogenase (IMPDH)
	mutant, D29G - Homo
	sapiens, 514 aa.
	[WO200185952-A2,
	15 NOV. 2001]
AAE18258	Human type I IMPDH	1 . . . 531	453/532 (85%)	0.0
	mutant, N109K - Homo	1 . . . 513	480/532 (90%)
	sapiens, 514 aa.
	[WO200185952-A2,
	15 NOV. 2001]
AAE18185	Human wild-type, type I	1 . . . 531	452/532 (84%)	0.0
	IMPDH #1 - Homo sapiens,	1 . . . 513	479/532 (89%)
	514 aa. [WO200185952-A2,
	15 NOV. 2001]
AAE18190	Human wild-type, type I	1 . . . 531	448/532 (84%)	0.0
	IMPDH #2 - Homo sapiens,	1 . . . 513	475/532 (89%)
	514 aa. [WO200185952-A2,
	15 NOV. 2001]

[0464] 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
AAH33622	IMP (inosine monophosphate)	1 . . . 531	454/532 (85%)	0.0
	dehydrogenase 1 - Homo sapiens	1 . . . 513	481/532 (90%)
	(Human), 514 aa.
P20839	Inosine-5′-monophosphate	1 . . . 531	452/532 (84%)	0.0
	dehydrogenase 1 (EC 1.1.1.205)	1 . . . 513	479/532 (89%)
	(IMP dehydrogenase 1) (IMPDH-I)
	(IMPD 1) - Homo sapiens (Human),
	514aa.
P50096	Inosine-5′-monophosphate	1 . . . 531	445/532 (83%)	0.0
	dehydrogenase 1 (EC 1.1.1.205)	1 . . . 513	479/532 (89%)
	(IMP dehydrogenase 1) (IMPDH-I)
	(IMPD 1) - Mus musculus (Mouse),
	514aa.
Q96NU2	CDNA FLJ30078 fis, clone	1 . . . 531	431/532 (81%)	0.0
	BGGI12000533, highly similar to	1 . . . 488	457/532 (85%)
	inosine-5′-monophosphate
	dehydrogenase 2 (EC 1.1.1.205) -
	Homo sapiens (Human), 489 aa.
P12268	Inosine-5′-monophosphate	1 . . . 531	395/532 (74%)	0.0
	dehydrogenase 2(EC 1.1.1.205)	1 . . . 513	452/532 (84%)
	(IMP dehydrogenase 2) (IMPDH-II)
	(IMPD 2) - Homo sapiens (Human),
	514aa.

[0465] PFam analysis predicts that the NOV21a protein contains the domains shown in the Table 21E.

TABLE 21E
Domain Analysis of NOV21a
		Identities/
		Similarities for
Pfam	NOV21a	the Matched	Expect
Domain	Match Region	Region	Value
IMPDH_N	21 . . . 116	49/97 (51%)	6.7e−40
		81/97 (84%)
CBS	118 . . . 186	16/69 (23%)	0.33
		50/69 (72%)
CBS	197 . . . 250	16/54 (30%)	1e−08
		43/54 (80%)
IMPDH_C	280 . . . 501	113/232 (49%)	6.7e−134
		202/232 (87%)

Example 22

[0466] 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:105	1387 bp
NOV22a,	GAATGTCTGACCCCCACAGCAGTCCTCTCCTGCCAGAGCCACTTTCCAGCAGATACAAACTCTACGA
CG140335-01
DNA Sequence	GGCAGAGTTTACCAGCCCGAGCTGGCCCTCGACATCCCCGGATACTCACCCAGCTCTGCCCCTCCTG
	GAAATGCCTGAAGAAAAGGATCTCCGGTCTTCCAATGAAGACAGTCACATTGTGAAGATCGAAAAGC
	TCAATGAAAGGAGTAAAAGGAAAGACGACGGGGTGGCCCATCGGGACTCAGCAGGCCAAAGGTGCAT
	CTGCCTCTCCAAAGCAGTGGGCTACCTCACGGGCGACATGAAGGAGTACAGGATCTGGCTTCCAGAC
	AAACCCGTGGTCCTCCAGTTCATTGACTGGATTCTCCGGCGCATATCCCAAGTCGTGTTCGTCAACA
	ACCCCGTCAGTGGAATCCTGATTCTGGTAGGACTTCTTGTTCAGAACCCCTGGTGGGCTCTCACTCG
	CTGGCTGGGAACAGTGGTCTCCACTCTGATGGCCCTCTTGCTCAGCCAGGACAGGTCTGCCATTGCC
	TCAGGACTCCATGGGTACAACGGGATGCTGGTGGGACTGCTGATGGCCGTGTTCTCGGAGAAGTTAG
	ACTACTACTGGTGCCTTCTGTTTCCTGTGACCTTCACAGCCATGTCCGGACCAGTTCTTTCTAGTGC
	CTTGAATTCCATCTTCAGCAAGTGGGACCTCCCCGTCTTCACTCTGCCCTTCAACATTGCAGTCACC
	TTGTACCTTGCAGCCACAGGCCACTACAACCTCTTCTTCCCCACAACACTGGTAGAGCCTGTGTCTT
	CAGTGCCCAATATCACCTGGACAGAGATGGAAATGCCCCTGCTGTTACAAGCCATCCCTGTTGGGGT
	CCGCCAGGTGTATGGCTGTGACAATCCCTGGACAGGCGGCGTGTTCCTGGTGGCTCTGTTCATCTCC
	TCGCCACTCATCTGCTTGCATGCAGCCATTGGCTCAATCGTGGGGCTGCTAGCAGCCCTGTCAGTGG
	CCACACCCTTCGAGACCATCTACACAGGCCTCTGGAGCTACAACTGCGTCCTCTCCTGCAPCGCCAT
	CGGAGGCATGTTCTATGCCCTCACCTGGCAGACTCACCTGCTCGCCCTCATCTGTGCCCTGTTCTGT
	GCATACATGGAAGCAGCCATCTCCAACATCATGTCAGTGGTAGGCGTGCCACCAGGCACCTGGGCCT
	TCTGCCTTGCCACCATCATCTTCCTGCTCCTGACGACAAACAACCCAGCCATCTTCAGACTCCCACT
	CAGCAAAGTCACCTACCCCGAGGCCAACCGCATCTACTACCTGACAGTGAAAAGCGGTGAAGAAGAG
	AAGGCCCCCAGCCGTGAATAGCCATGTTCGGGGAAGAAACGCTCTTT
	ORF Start: ATG at 3		ORF Stop: TAG at 1359
	SEQ ID NO:106	452 aa	MW at 49740.4 kD
NOV22a,	MSDPHSSPLLPEPLSSRYKLYEAEFTSPSWPSTSPDTHPALPLLEMPEEKDLRSSNEDSHIVKIEKL
CG140335-01
Protein Sequence	NERSKRKDDGVAHRDSAGQRCICLSKAVGYLTGDMKEYRIWLPDKPVVLQFTDWILRGISQVVFVNN
	PVSGILILVGLLVQNPWWALTGWLGTVVSTLMALLLSQDRSAIASGLHGYNGMLVGLLMAVFSEKLD
	YYWWLLFPVTFTAMSGPVLSSALNSIFSKWDLPVFTLPFNIAVTLYLAATGHYNLEFPTTLVEPVSS
	VPNITWTEMEMPLLLQAIPVGVGQVYGCDNPWTGGVFLVALFISSPLICLHAAIGSIVGLLAALSVA
	TPFETIYTGLWSYNCVLSCIAICGMFYALTWQTHLLALICALFCAYMEAAISNIMSVVGVPPGTWAF
	CLATIIFLLLTTNNPAIFRLPLSKVTYPEANRIYYLTVKSGEEEKAPSGE

[0467] Further analysis of the NOV22a protein yielded the following properties shown in Table 22B.

TABLE 22B
Protein Sequence Properties NOV22a
PSort     0.6000 probability located in plasma membrane;
analysis: 0.4000 probability located in Golgi body; 0.3000
          probability located in endoplasmic reticulum
          (membrane); 0.0300 probability located in mito-
          chondrial inner membrane
SignalP   No Known Signal Sequence Predicted
analysis:

[0468] 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
			Identities/
			Similarities for
Geneseq	Protein/Organism/Length	NOV22a Residues/	the Matched	Expect
Identifier	[Patent #, Date]	Match Residues	Region	Value
AAE22853	Human transporter protein -	1 . . . 452	431/452 (95%)	0.0
	Homo sapiens, 452 aa.	1 . . . 452	441/452 (97%)
	[WO200220763-A2, 14 MAR. 2002]
AAW13742	Urea transporter polypeptide -	57 . . . 439	271/383 (70%)	e−164
	Oryctolagus cuniculus, 397 aa.	2 . . . 378	329/383 (85%)
	[US5441875-A, 15 AUG. 1995]
ABP40193	Staphylococcus epidermidis ORF	114 . . . 419	82/312 (26%)	3e−24
	amino acid sequence SEQ ID	4 . . . 305	150/312 (47%)
	NO: 5038 - Staphylococcus
	epidermidis, 305 aa.
	[US6380370-B1, 30 APR. 2002]
AAU32094	Novel human secreted protein	352 . . . 391	21/40 (52%)	3e−04
	#2585 - Homo sapiens, 70 aa.	6 . . . 45	28/40 (69%)
	[WO200179449-A2, 25 OCT. 2001]
ABB48958	Listeria monocytogenes protein	121 . . . 197	24/78 (30%)	0.29
	#1662 - Listeria monocytogenes,	26 . . . 98	43/78 (54%)
	357 aa. [WO200177335-A2,
	18 OCT. 2001]

[0469] 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
			Identities/
Protein			Similarities for
Accession		NOV22a Residues/	the Matched	Expect
Number	Protein/Organism/Length	Match Residues	Portion	Value
Q96PH5	Urea transporter UT-A1 -	1 . . . 451	429/451 (95%)	0.0
	Homo sapiens (Human), 920 aa.	1 . . . 451	439/451 (97%)
Q9ES04	Urea transporter isoform	1 . . . 452	362/452 (80%)	0.0
	UTA-3 - Mus musculus (Mouse),	10 . . . 461	413/452 (91%)
	461 aa.
Q8R4T9	Urea transporter isoform	1 . . . 451	362/451 (80%)	0.0
	UT-A1 - Mus musculus (Mouse),	10 . . . 460	412/451 (91%)
	930 aa.
Q9R1Y7	Urea transporter UT-A3 -	1 . . . 452	360/452 (79%)	0.0
	Rattus norvegicus (Rat),	9 . . . 460	410/452 (90%)
	460 aa.
Q9Z2R3	Urea transporter UT4 - Rattus	1 . . . 452	359/452 (79%)	0.0
	norvegicus (Rat), 460 aa.	9 . . . 460	409/452 (90%)

[0470] PFam analysis predicts that the NOV22a protein contains the domains shown in the Table 22E.

TABLE 22E
Domain Analysis of NOV22a
		Identities/
		Similarities for
Pfam	NOV22a	the Matched	Expect
Domain	Match Region	Region	Value
No Significant Matches Found to Publically Available Domains

Example 23

[0471] 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:107	534 bp
NOV23a,	GCCTCCAGGGGCCCCATACTATCAGCTATGGTCAACCCCACCAAGTTCTTCAATGAGCCCTGGGGCC
CG140355-01
DNA Sequence	GCATCTCCATCCAGCTGTTTGCAGACAAGTTTCCAAAGACAGCAGAAAATGTTTGTGCTCTGAGCAT
	TCGAGAGAAAGGATTTGGTTATAACGGTTCCTGCTTTCACAGAATTATTCCGGGGTTTATGTGTCAC
	GGTGGTGACTTCACACACCATAATGGCAGTGGTGGCAAGTACATCTATGCGGAGAAATTTGATGATG
	AGAACTTCATCCTGAAGCAGACAGGTTCTGGCATCTTGTCCAAGGAAAATGCTGGACCCAACACAAA
	CGGTTCCCAGTTTTTCATCTGCAGTGCCAAGAGTGAGTGGTTCGATCGTGAGCATGTGTTCTTTGGC
	AAGGTGAAAGAAGGCATGAATATTGTGGAGGCCATGGAGGGTTTTGGGTCCAGGAATGGCAAGACCA
	GCAAGAAGATCACCATTGCTGACTGTTGACAACTCTAATAAGCTTGACTTGTGTTCGTTTTGTTT
	ORE Start: ATG at 28		ORE Stop: TGA at 496
	SEQ ID NO: 108	156 aa	MW at 17164.3 kD
NOV23a,	MVNPTKFFNEPWGRISIQLFADKFPKTAENVCALSIGEKGFGYKGSCFHRIIPGFMCNGGDFTHHNG
CG140355-01
Protein Sequence	SGGKYIYGEKFDDENFILKQTGSGILSKENAGPNTNGSQFFICSAKSEWLDGEHVFFGKVXEGNNIV
	EAMEGFGSRNGKTSKKITIADC

[0472] Further analysis of the NOV23a protein yielded the following properties shown in Table 23B.

TABLE 23B
Protein Sequence Properties NOV23a
PSort     0.6400 probability located in microbody (peroxisome);
analysis: 0.4500 probability located in cytoplasm; 0.1000
          probability located in mitochondrial matrix
          space; 0.1000 probability located in lysosome (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0473] 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
			Identities/
			Similarities for
Geneseq	Protein/Organism/Length	NOV23a Residues/	the Matched	Expect
Identifier	[Patent #, Date]	Match Residues	Region	Value
ABG29319	Novel human diagnostic protein	1 . . . 156	156/156 (100%)	2e−92
	#29310 - Homo sapiens, 407 aa.	252 . . . 407	156/156 (100%)
	[WO200175067-A2, 11 OCT. 2001]
ABG27276	Novel human diagnostic protein	1 . . . 156	156/156 (100%)	2e−92
	#27267 - Homo sapiens, 407 aa.	252 . . . 407	156/156 (100%)
	[WO200175067-A2, 11 OCT. 2001]
AAU01195	Human cyclophilin A protein -	1 . . . 156	132/161 (81%)	5e−74
	Homo sapiens, 165 aa.	1 . . . 161	140/161 (85%)
	[WO200132876-A2, 10 MAY 2001]
AAW56028	Calcineurin protein - Mammalia,	1 . . . 156	132/161 (81%)	5e−74
	165 aa. [WO9808956-A2,	1 . . . 161	140/161 (85%)
	05 MAR. 1998]
AAR13726	Bovine cyclophilin - Bos taurus,	2 . . . 156	132/160 (82%)	6e−74
	163 aa. [US5047512-A,	1 . . . 160	139/160 (86%)
	10 SEP. 1991]

[0474] 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
			Identities/
Protein			Similarities for
Accession		NOV23a Residues/	the Matched	Expect
Number	Protein/Organism/Length	Match Residues	Portion	Value
CAC39529	Sequence 26 from Patent	1 . . . 156	132/161 (81%)	1e−73
	WO0132876 - Homo sapiens	1 . . . 161	140/161 (85%)
	(Human), 165 aa.
P04374	Peptidyl-prolyl cis-trans	2 . . . 156	132/160 (82%)	2e−73
	isomerase A (EC 5.2.1.8)	1 . . . 160	139/160 (86%)
	(PPIase) (Rotamase)
	(Cyclophilin A) (Cyclo-
	sporin A-binding protein) -
	Bos taurus (Bovine), and,
	163 aa.
Q9BRU4	Peptidylprolyl isomerase A	1 . . . 156	131/161 (81%)	5e−73
	(cyclophilin A) - Homo	1 . . . 161	139/161 (85%)
	sapiens (Human), 165 aa.
P05092	Peptidyl-prolyl cis-trans	2 . . . 156	131/160 (81%)	5e−73
	isomerase A (EC 5.2.1.8)	1 . . . 160	139/160 (86%)
	(PPIase) (Rotamase)
	(Cyclophilin A) (Cyclo-
	sporin A-binding protein) -
	Homo sapiens (Human),, 164 aa.
Q96IX3	Peptidylprolyl isomerase A	1 . . . 156	131/161 (81%)	2e−72
	(cyclophilin A) - Homo	1 . . . 161	139/161 (85%)
	sapiens (Human), 165 aa.

[0475] PFam analysis predicts that the NOV23a protein contains the domains shown in the Table 23E.

TABLE 23E
Domain Analysis of NOV23a
		Identities/
		Similarities for
Pfam	NOV23a	the Matched	Expect
Domain	Match Region	Region	Value
pro_isomerase	10 . . . 156	95/166 (57%)	1.2e−75
		128/166 (77%)

Example 24

[0476] 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:109	900 bp
NOV24a,	GCTAAGATTGCTACCTGGACTTTCGTTGACCATGCTGTCCCGGGTGGTACTTTCCGCCGCCGCCACA
CG140612-01
DNA Sequence	GCGGCCCCCTCTCTGAAGAATGCAGCCTTCCTAGGTCCAGGGGTATTGCACGCAACAAGGACCTTTC
	ATACAGGGCAGCCACACCTTGTCCCTGTACCACCTCTTCCTGAATACGGAGGAAAAGTTCGTTATGG
	ACTGATCCCTGAGGAATTCTTCCAGTTTCTTTATCCTAAAACTGGTGTAACAGGGCCCTATGTACTC
	GGAACTGGGCTTATCTTGTACGCTTTATCCAAAGAAATATATGTGATTAGCGCAGAGACCTTCACTG
	CCCTATCAGTACTAGGTGTAATGGTCTATGGAATTAAAAAATATGGTCCCTTTGTTGCAGACTTTGC
	TGATAAACTCAATGAGCAAAAACTTGCCCAACTAGAAGAGGCGAACCAGGCTTCCATCCAACACATC
	CGGAATGCAATTGATACGGAGAAGTCACAACAGGCACTGGTTCAGAAGCGCCATTACCTTTTTGATG
	TGCAAAGGAATAACATTGCTATGGCTTTGGAAGTTACTTACCGGGAACGACTGTATAGAGTATATAA
	GGAAGTAAAGAATCGCCTGGACTATCATATATCTGTGCAGAACATGATGCGTCGAAAGGAACAAGAA
	CACATGATAAATTGGGTGGAGAAGCACGTGGTGCAAAGCATCACCACACAGCAGGAAAAGGAGACAA
	TTGCCGAGTGCATTGCGGACCTAAAGCTGCTGGCAAAGAAGGCCCAAGCACAGCCAGTTATGTAAAT
	GTATCTATCCCAATTGAGACAGCTAGAAACAGTTGACTGACTAAATGGAAACTAGTCTATTTGACAA
	AGTCTTTCTGTGTTGGTGTCTACTGAAGT
	ORF Start: ATG at 32		ORF Stop: TAA at 800
	SEQ ID NO:110	256 aa	MW at 28951.4 kD
	NOV24a, MLSRVVLSAAATAAPSLKNAAFLGPGVLQATRTFHTGQPHLVPVPPLPEYGGKVRYGLIPEEFFQFL
	CG140612-01
	Protein Sequence	YPKTGVTGPYVLGTGLILYALSKEIYVISAETFTALSVLGVMVYGIKKYGPFVADFADKLNEQKLAQ
		LEEAKQASIQHIRNAIDTEKSQQALVQKRHYLFDVQRNNIAMALEVTYRERLYRVYKEVKNRLDYHI
		SVQNMMRRKEQEHMINWVEKHVVQSTTTQQEKETIAECIADLKLLAKKAQAQPVM
	SEQ ID NO:111	894 bp
NOV24b,	GCTAAGATTGCTACCTGGACTTTCGTTGACCATGCTGTCCCGGGTGGTACTTTCCGCCGCCGCCACA
CG140612-02
DNA Sequence	GCGGCCCCCTCTCTGAAGAATGCAGCCTTCCTAGGTCCAGCGGTATTGCAGGCAACAAGGACCTTTC
	ATACAGGGCAGCCACACCTTGTCCCTGTACCACCTCTTCCTGAATACGGAGGAAAAGTTCGTTATGG
	ACTGATCCCTGAGGAATTCTTCCAGTTTCTTTATCCTAAAACTGGTGTAACAGGACCCTATGTACTC
	GGAACTGGGCTTATCTTGTACGCTTTATCCAAAGAAATATATGTGATTAGCGCAGAGACCTTCACTG
	CCCTATCAGTACTAGGTGTAATGGTCTATGGAATTAAAAAATATGGTCCCTTTGTTGCAGACTTTGC
	TGATAAACTCAATGAGCAAAAACTTGCCCAACTAGAAGAGGCGAAGCAGGCTTCCATCCAACACATC
	CAGAATGCAATTGATACGGAGAAGTCACAACAGGCACTGGTTCAGAAGCGCCATTACCTTTTTGATG
	TGCAAAGGAATAACATTGCTATGGCTTTGGAAGTTACTTACCGGGAACGACTGTATAGAGTATATAA
	GGAAGTAAAGAATCGCCTGGACTATCATATATCTGTGCAGAACATGATGCGTCGAAAGGAACACATG
	ATAAATTGGGTGGAGAAGCACGTGGTGCAAAGCATCTCCACACAGCAGGAAAAGGAGACAATTGCCA
	AGTGCATTGCGGACCTAAAGCTGCTGGCAAAGAAGGCTCAAGCACAGCCAGTTATGTAAATGTATCT
	ATCCCAATTGAGACAGCTAGAAACAGTTGACTGACTAAATGGAAACTAGTCTATTTGACAAAGTCTT
	TCTGTGTTGGTGTCTACTGAAGT
	ORE Start: ATG at 32		ORF Stop: TAA at 794
	SEQ ID NO:112	254 aa	MW at 28651.1 kD
NOV24b,	MLSRVVLSAAATAAPSLKNAAFLGPGVLQATRTFHTGQPHLVPVPPLPEYGGKVRYGLIPEEFFQFL
CG140612-02
Protein Sequence	YPKTGVTGPYVLGTGLILYALSKEIYVISAETFTALSVLGVMVYGIKKYGPFVADFADKLNEQKLAQ
	LEEAKQASIQHIQNAIDTEKSQQALVQKRHYLFDVQRNNIAMALEVTYRERLYRVYKEVKNRLDYHI
	SVQNMMRRKEHMINWVEKHVVQSISTQQEKETIAKCIADLKLLAKKAQAQPVM

[0477] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 24B.

TABLE 24B
Comparison of NOV24a against NOV24b.
			Identities/
			Similarities for
	Protein	NOV24a Residues/	the Matched
	Sequence	Match Residues	Region
	NOV24b	1 . . . 256	240/256 (93%)
		1 . . . 254	243/256 (94%)

[0478] Further analysis of the NOV24a protein yielded the following properties shown in Table 24C.

TABLE 24C
Protein Sequence Properties NOV24a
PSort     0.5326 probability located in outside; 0.1000
analysis: probability located in endoplasmic reticulum
          (membrane); 0.1000 probability located in
          endoplasmic reticulum (lumen); 0.1000
          probability located in lysosome (lumen)
SignalP   Cleavage site between residues 14 and 15
analysis:

[0479] 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	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAG03729	Human secreted protein, SEQ	1 . . . 132	126/132 (95%)	4e−67
	ID NO: 7810 - Homo	1 . . . 132	127/132 (95%)
	sapiens, 134 aa.
	[EP1033401-A2,
	06 SEP. 2000]
AAU32833	Novel human secreted	1 . . . 253	169/282 (59%)	1e−66
	protein #3324 - Homo	10 . . . 290	188/282(65%)
	sapiens, 292 aa.
	[WO200179449-A2,
	25 OCT. 2001]
ABG17750	Novel human diagnostic	72 . . . 230	117/159 (73%)	3e−59
	protein #17741 - Homo	206 . . . 360	134/159 (83%)
	sapiens, 360 aa.
	[WO200175067-A2,
	11 OCT. 2001]
AAU32832	Novel human secreted	2 . . . 104	102/103 (99%)	4e−53
	protein #3323 - Homo	1 . . . 103	103/103 (99%)
	sapiens, 114 aa.
	[WO200179449-A2,
	25 OCT. 2001]
ABB63734	Drosophila melanogaster	48 . . . 252	94/206 (45%)	1e−47
	polypeptide SEQ ID NO	38 . . . 242	138/206 (66%)
	17994 - Drosophila
	melanogaster, 243 aa.
	[WO200171042-A2,
	27 SEP. 2001]

[0480] 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
P24539	ATP synthase B chain,	1 . . . 256	253/256 (98%)	e−142
	mitochondrial precursor (EC	1 . . . 256	256/256 (99%)
	3.6.3.14) - Homo sapiens
	(Human), 256 aa.
JQ1144	H+-transporting ATP	1 . . . 256	252/256 (98%)	e−142
	synthase (EC 3.6.1.34) chain	1 . . . 256	256/256 (99%)
	b precursor, mitochondrial -
	human, 256 aa.
Q9CQQ7	ATP synthase B chain,	1 . . . 256	209/256 (81%)	e−118
	mitochondrial precursor (EC	1 . . . 256	234/256 (90%)
	3.6.3.14) - Mus musculus
	(Mouse), 256 aa.
P19511	ATP synthase B chain,	1 . . . 256	207/256 (80%)	e−118
	mitochondrial precursor (EC	1 . . . 256	234/256 (90%)
	3.6.3.14) - Rattus norvegicus
	(Rat), 256 aa.
P13619	ATP synthase B chain,	43 . . . 256	182/214 (85%)	e−102
	mitochondrial (EC 3.6.3.14) -	1 . . . 214	201/214 (93%)
	Bos taurus (Bovine), 214 aa.

[0481] PFam analysis predicts that the NOV24a protein contains the domains shown in the Table 24F.

TABLE 24F
Domain Analysis of NOV24a
		Identities/
	NOV24a	Similarities
Pfam	Match	for the Matched	Expect
Domain	Region	Region	Value
No Significant Matches Found to Publically Available Domains

Example 25

[0482] 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:113	1316 bp
NOV25a,	TCCTACCACAGTGTCTGATGGAGCTTTCCTACCAGACCCTGAAATTCACCCATCACGCGCGGGAAGC
CG140696-01
DNA Sequence	GAGCGAGATGAGGACAGAAGCACGACGAAAAAATCTTCTCATTTTGATTTCGCATTATTTAACACAA
	GAAGGGTATCTCGATACAGCAAATGCTTTGGAGCAAGAAACTAAACTGGGGTTACGACGGTTTGAAG
	TTTCTGACAACATTGATCTTGAAACTATTTTGATGGAATATGAGAGTTATTATTTTGTAAAATTTCA
	GAAATACCCCAAAATTGTCAAAAAGTCATCAGACACAGCAGAAAATAATTTACCGCAAAGAAGTAGA
	GGGAAGACCAGAAGGATGATGAACGACAGTTGTCAAAATCTTCCCAAGATCAATCAGCAGAGGCCCC
	GGTCCAAAACCACAGCGGGGAAGACAGCGGACACCAAATCGCTCAAAAAGCATCTATTGCAGGTCTT
	AGAGTCAGTCTCTAACACTCGCCTGGAAAGTGCCAACTTCGGCCTACATATATCAAGAATCCGTAAA
	GACAGTGGAGAGGAAAATGCCCACCCACGAAGACGCCAAATCATTGACTTCCAAGGGCTGCTCACAG
	ATGCCATCAAGGGAGCAACCAGTGAACTTGCCTTGAACACCTTCGACCATAATCCAGACCCCTCAGA
	ACGACTCCTGAAACCTCTGAGTGCATTTATTGGCATGAACAGTGAGATGCGAGAATTGGCAGCCGTG
	GTGAGCCGGGACATTTATCTCCATAATCCAAACATAAAGTGGAATGACATTATTGGACTTGATGCAG
	CCAAGCAGTTAGTCAAAGAAGCTGTTGTGTATCCTATAAGGTATCCACAGCTATTTACAGGAATTCT
	TTCTCCCTGGAAAGGACTACTGCTGTACGGCCCTCCAGGTACAGGAAAGACTTTACTGGCCAAAGCT
	CTGGCCACTGAATGTAAAACAACCTTCTTTAACATTTCTGCATCCACCATTGTCAGCAAATGGAGAG
	GGGATTCAGAAAAACTCGTTCGGGTGTTATTTGAGCTTGCCCGCTACCACGCCCCATCCACGATCTT
	CCTGGACGAGCTGGAGTCGGTGATGAGTCAGAGAGGCACAGCTTCTGGGGGAGAACATGAACGAAGC
	CTGCGGATGAAGACAGAGTTACTGGTGCAGATGGATGGGCTGGCACGCTCAGAAGATCTCGTATTTG
	TCTTAGCAGCTTCTAACCTGCCGTGGTAAGAGACCAAGAGAGTAAATTTTGAATACATTTTCAGGAG
	TCACTAAGTGCAAATAAAAATTTTATATTGACCACTTCAAAAA
	ORF Start: ATG at 18		ORF Stop: TAA at 1233
	SEQ ID NO:114	405 aa	MW at 45796.9 kD
NOV25a,	MELSYQTLKFTHQAREASEMRTEARRKNLLILISHYLTQEGYLDTANALEQETKLGLRRFEVCDNID
CG140696-01
Protein Sequence	LETILMEYESYYFVKFQKYPKIVKKSSDTAENNLPQRSRGKTRRMMNDSCQNLPKINQQRPRSKTTA
	GKTGDTKSLKKHLLQVLESVSNTRLESANFGLHISRIRKDSGEENANPRRGQIIDFQGLLTDAIKGA
	TSELALNTFDHNPDPSERLLKPLSAFIGMNSEMRELAAVVSRDTYLHNPNIKWNDIIGLDAAKQLVK
	EAVVYPIRYPQLFTGILSPWKGLLLYGPPGTGKTLLAKAVATECKTTFFNISASTIVSKWRGDSEKL
	VRVLFELARYHAPSTIFLDELESVMSQRGTASGGEHEGSLRMKTELLVQMDGLARSEDLVFVLAASN
	LPW
	SEQ ID NO:115	1035 bp
NOV25b,	TCCTAGCACAGTGTCTGATGGAGCTTTCCTACCAGACCCTGAAATTCACGCATCAGGCGCGGGAAGC
CG140696-02
DNA Sequence	GACTGATGAACGACAGTTGTCAAAATCTTCCCAAGATCAATCAGCAGAGGCCCCGGTCCAAAACCAC
	AGCCGGGGCAAGACACGGGGACACCAAATCGCTCAATAAGGAGCATCCTAATCAGGAGGTAGTTGAT
	AACACTCGCCTGCAAAGTGCCAACTTCGGCCTACATATATCAAGAATCCGTAAAGACAGTGGAGAGG
	AAAATGCCCACCCACGAAGAGGCCAAATCATTGACTTCCAAGGGCTGCTCACAGATGCCATCAAGGG
	AGCAACCAGTGAACTTGCCTTGAACACCTTCGACCATAATCCAGACCCCTCAGAACGACTGCTGAAA
	CCTCTGAGTGCATTTATTGGCATGAACAGTGAGATGCGAGAATTGGCAGCCGTGGTGAGCCGGGACA
	TTTATCTCCATAATCCAAACATAAAGTGGAATGACATTATTGGACTTGATGCAGCCAAGCAGTTAGT
	CAAAGAAGCTGTTGTGTATCCTATAAGGTATCCACAGCTATTTACAGGAATTCTTTCTCCCTGGAAA
	GGACTACTGCTGTACGGCCCTCCAGGTACAGGAAAGACTTTACTGGCCAAAGCTGTGCCCACTGAAT
	GTAAAACAACCTTCTTTAACATTTCTGCATCCACCATTGTCAGCAAATGGAGAGGGGATTCAGAAAA
	ACTCGTTCGGGTGTTATTTGAGCTTGCCCGCTACCACGCCCCATCCACGATCTTCCTGGACGAGCTG
	GAGTCGGTGATGAGTCAGAGAGGCACAGCTTCTGGGGGAGAACATGAAGGAAGCCTGCGGATGAAGA
	CAGAGTTACTGGTGCAGATGGATGGGCTGGCACCCTCAGAAGATCTCGTATTTGTCTTAGCAGCTTC
	TAACCTGCCCTGGTAACAGACCAACAGAGTAAATTTTGAATACATTTTCAGGAGTCACTAAGTGCAA
	ATAAAAATTTTATATTGACCACTTCAAAAA
	ORF Start: ATG at 73		ORF Stop: TAA at 952
	SEQ ID NO:116	293 aa	MW at 32516.6 kD
NOV2Sb,	MNDSCQNLPKINQQRPRSKTTAGARHGDTKSLNKEHPNQEVVDNTRLESANFGLHISRIRKDSGEEN
CG140696-02
Protein Sequence	AHPRRGQIIDFQGLLTDAIKGATSELALNTFDHNPDPSERLLKPLSAFIGMNSEMRELAAVVSRDIY
	LHNPNIKWNDIIGLDAAKQLVKEAVVYPTRYPQLFTGILSPWKGLLLYGPPGTGKTLLAKAVATECK
	TTFFNISASTIVSKWRGDSEKLVRVLFELARYHAPSTIFLDELESVMSQRGTASGGEHEGSLRNKTE
	LLVQMDGLARSEDLVFVLAASNLPW
	SEQ ID NO:117	1215 bp
NOV25c,	ATGGAGCTTPCCTACCAGACCCTGAAATTCACGCATCAGGCGCGGGAAGCGTGCGAGATGAGGACAG
CG140696-03
DNA Sequence	AAGCACGACGAAAAAATCTTCTCATTTTGATTTCCCATTATTTAACACAAGAAGGGTATATCGATAC
	AGCAAATGCTTTGGAGCAAOAAACTAAACTGGGGTTACGACGGTTTGAAGTTTGTGACAACATTGAT
	CTTGAAACTATTTTGATGGAATATGAGAGTTATTATTTTGTAAAATTTCAGAAATACCCCAAAATTG
	TCAAAAAGTCATCAGACACAGCAGAAAATAATTTACCGCAAAGAAGTAGAGGGAAGACCAGAAGGAT
	GATGAACGACAGTTGTCAAAATCTTCCCAAGATCAATCAGCAGAGGCCCCGGTCCAAAACCACAGCG
	GGGAAGACAGGGGACACCAAATCGCTCAATAAGGAGCATCCTAATCACGAGGTAGTTGATAACACTC
	GCCTCGAAAGTGCCAACTTCGGCCTACATATATCAAGAATCCGTAAAGACAGTGGAGACGAAAATGC
	CCACCCACGAAGAGGCCAAATCATTGACTTCCAAGGGCTGCTCACAGATGCCATCAAGGGAGCAACC
	AGTGAACTTGCCTTGAACACCTTCGACCATAATCCAGACCCCTCAGAACGACTGCTGAAACCTCTGA
	GTGCATTTATTGGCATGAACAGTGAGATGCGAGAATTGGCAGCCGTGGTGAGCCGGGACATTTATCT
	CCATAATCCAAACATAAAGTGGAATGACATTATTGGACTTGATGCAGCCAAGCAGTTAGTCAAAGAA
	GCTGTTGTGTATCCTATAAGGTATCCACAGCTATTTACAGGAATTCTTTCTCCCTGGAAAGGACTAC
	TGCTGTACGGCCCTCCAGGTACAGGAAAGACTTTACTGGCCAAAGCTGTGGCCACTGAATGTAAAAC
	AACCTTCTTTAACATTTCTGCATCCACCATTGTCAGCAAATGGAGAGGGGATTCAGAAAAACTCGTT
	CGGGTGTTATTTGAGCTTGCCCCCTACCACGCCCCATCCACGATCTTCCTGGACGAGCTGGAGTCGG
	TGATGAGTCAGAGAGGCACAGCTTCTGGFGGAGAACATGAAGGAAGCCTGCGGATGAAGACAGAGTT
	ACTGGTGCAGATGGATGGGCTGGCACGCTCAGAAGATCTCGTATTTGTCTTAGCAGCTTCTAACCTG
	CCGTGGTAA
	ORF Start: ATG at 1		ORF Stop: TAA at 1213
	SEQ ID NO:118	404 aa	MW at 45740.7 kD
NOV25c,	MELSYQTLKFTHQAREACEMRTEARRKNLLILISHYLTQEGYIDTANALEQETKLGLRRFEVCDNID
CG140696-03
Protein Sequence	LETILMEYESYYFVKFQKYPKIVKKSSDTAENNLPQRSRGKTRRMMNDSCQNLPKINQQRPRSKTTA
	GKTGDTKSLNKEHPNQEVVDNTRLESANFGLHISRIRKDSGEENAHPRRGQIIDFQGLLTDAIKGAT
	SELALNTFDHNPDPSERLLKPLSAFIGMNSEMRELAAVVSRDIYLHNPNIKWNDIIGLDAAKQLVKE
	AVVYPIRYPOLFTGILSPWKGLLLYGPPGTGKTLLAKAVATECKTTFFNISASTIVSKWRGDSEKLV
	RVLFELARYHAPSTIFLDELESVMSQRGTASGGEHEGSLRMXTELLVQNDGLARSEDLVFVLAASNL
	PW

[0483] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 25B.

TABLE 25C
Protein Sequence Properties NOV25a
PSort     0.6500 probability located in cytoplasm; 0.1000
analysis: 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:

[0484] Further analysis of the NOV25a protein yielded the following properties shown in Table 25C.

TABLE 25D
Geneseq Results for NOV25a
		NOV25a	Identities/
		Residues/	Similarities
Geneseq	Protein/Organism/Length	Match	for the	Expect
Identifier	[Patent #, Date]	Residues	Matched Region	Value
AAG67151	Amino acid sequence of a	1 . . . 405	394/406 (97%)	0.0
	human enzyme - Homo	1 . . . 403	396/406 (97%)
	sapiens, 403 aa.
	[WO200164896-A2,
	07 SEP. 2001]
AAB69399	Human retinoid receptor	230 . . . 405	176/176 (100%)	4e−97
	interacting protein #2 -	1 . . . 176	176/176 (100%)
	Homo sapiens, 176 aa.
	[WO200112786-A1,
	22 FEB. 2001]
AAG48014	Arabidopsis thaliana protein	231 . . . 405	122/175 (69%)	5e−69
	fragment SEQ ID NO: 60587 -	7 . . . 181	150/175 (85%)
	Arabidopsis thaliana, 312
	aa. [EP1033405-A2,
	06 SEP. 2000]
AAG48013	Arabidopsis thaliana protein	231 . . . 405	122/175 (69%)	5e−69
	fragment SEQ ID NO: 60586 -	88 . . . 262	150/175 (85%)
	Arabidopsis thaliana, 393
	aa. [EP1033405-A2,
	06 SEP. 2000]
AAG31755	Arabidopsis thaliana protein	231 . . . 405	122/175 (69%)	5e−69
	fragment SEQ ID NO: 38188 -	7 . . . 181	150/175 (85%)
	Arabidopsis thaliana, 312
	aa. [EP1033405-A2,
	06 SEP. 2000]

[0485] A search of the NOV25a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 25D.

[0486] 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 25E.

TABLE 25E
Public BLASTP Results for NOV25a
		NOV25a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9D3R6	4933439B08Rik protein -	1 . . . 405	354/405 (87%)	0.0
	Mus musculus(Mouse), 409	1 . . . 405	374/405 (91%)
	aa.
Q9GNC3	Probable AAA ATPase	8 . . . 405	184/427 (43%)	9e−82
	(Probable katanin-like	22 . . . 429	256/427 (59%)
	protein) - Leishmania major,
	565 aa.
Q8S0S5	Katanin p60 subunit A 1-like -	211 . . . 405	131/195 (67%)	8e−70
	Oryza saliva (japonica	104 . . . 293	161/195 (82%)
	cultivar-group), 428 aa.
B84758	probable katanin [imported] -	231 . . . 405	122/175 (69%)	2e−68
	Arabidopsis thaliana, 393 aa.	88 . . . 262	150/175 (85%)
O64691	Putative katanin - Arabidopsis	231 . . . 405	122/175 (69%)	2e−68
	thaliana(Mouse-ear cress),	79 . . . 253	150/175 (85%)
	384 aa.

[0487] PFam analysis predicts that the NOV25a protein contains the domains shown in the Table 25F.

TABLE 25F
Domain Analysis of NOV25a
			Identities/
			Similarities
		NOV25a	for the
		Match	Matched	Expect
	Pfam Domain	Region	Region	Value
	Sigma54_activat	291 . . . 308	10/18 (56%)	0.94
			16/18 (89%)
	AAA	290 . . . 405	59/220 (27%)	6.8e−13
			99/220 (45%)

Example 26

[0488] 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:119	3915 bp
NOV26a,	ATACCTACTGAACGTGAACGAACAGAAAGGCTAATTAAAACCAAATTAAGGGAGATCATGATGCAGA
CG140747-01
DNA Sequence	AGGATTTCGAGAATATTACATCCAAAGAGATAAGAACAGAGTTGGAAATGCAAATGGTGTGCAACTT
	GCGGGAATTCAACGAATTTATAGACAATGAAATGATAGTGATCCTTGGTCAAATGGATAGCCCTACA
	CAGATATTTGACCATGTGTTCCTGGGCTCAGAATGGAATGCCTCCAACTTAGAGGACTTACAGAACC
	GAGGGGTACGGTATATCTTGAATGTCACTCGAGAGATAGATAACTTCTTCCCAGGAGTCTTTGAGTA
	TCATAACATTCGGGTATATGATGAAGAGGCAACGGATCTCCTGGCGTACTGGAATGACACTTACAAA
	TTCATCTCTAAAGCAAAGAAACATGGATCTAAATGCCTTGTGCACTGCAAAATGGGGGTGAGTCGCT
	CAGCCTCCACCGTGATTGCCTATGCAATGAAGGAATATGGCTGGAATCTGGACCGAGCCTATGACTA
	TGTGAAACAAAGACGAACGGTAACCAAGCCCAACCCAAGCTTCATGAGACAACTGGAAGAGTATCAG
	GGGATCTTGCTGGCAAGCAAACAGCGGCATAACAAACTATGGAGATCTCATTCAGATAGTGACCTCT
	CAGACCACCACGAACCCATCTGCAAACCTGGGCTAGAACTCAACAAGAAGGATATCACCACCTCAGC
	AGACCAGATTGCTGAGGTGAAGACCATGGAGAGTCACCCACCCATACCTCCTGTCTTTGTGCAACAT
	ATGGTCCCACAAGATGCAAATCAGAAAGGCCTGTGTACCAAAGAAAGAATGATCTGCTTGGAGTTTA
	CTTCTAGGGAATTTCATGCTGGACAGATTGAGGATGAATTAAACTTAAATGACATCAATGGATGCTC
	ATCAGGGTGTTGTCTGAATGAATCAAAATTTCCTCTTGACAATTGCCATGCATCCAAAGCCTTAATT
	CAGCCTGGACATGTCCCAGAAATGGCCAACAAGTTTCCAGACTTAACAGTGGAAGATTTGGAGACAG
	ATGCACTGAAAGCAGACATGAATGTCCACCTACTGCCTATGGAAGAATTGACATCTCCACTGAAAGA
	CCCCCCCCATGTCCCCTGATCCTGAGTCACCAAGCCCCCAACCAGTTGCCAGACTGAAATCTCAGAT
	TTCAGTACAGATCGCATTGACTTTTTTAGTGCCCTAGAGAAGTTTGTGGAGCTCTCCCAAGAAACCC
	GGTCACGATCTTTTTCCCATTCAAGGATGGAGGAACTGGGTGGAGGAAGGAATGAGAGCTGTCGACT
	GTCAGTGGTAGAAGTAGCCCCTTCCAAAGTGACAGCTGATGACCAGAGAAGCAGCTCTTTGAGTAAT
	ACTCCCCATGCATCAGAAGAATCTTCAATGGATGAGGAACAGTCAAAGGCAATTTCAGAACTGGTCA
	GCCCAGACATCTTCATGCAGTCTCACTCGGAAAATGCAATTTCAGTCAAAGAAATTGTCACTGAAAT
	TGAGTCCATCAGTCAAGGAGTTGCGCAGATTCAACTGAAAGGAGACATCTTACCCAACCCATGCCAT
	ACACCAAAGAAGAACAGCATCCATGAGCTGCTCCTTGAGAGGGCCCAGACTCCAGAGAACAAACCTG
	GACATATGGAGCAAGATGAGGACTCCTGCACAGCCCAGCCTGAACTAGCCAAAGACTCAGGGATGTG
	CAACCCAGAAGGCTGCCTAACCACACACTCATCTATAGCAGACTTCGAAGAAGGGGAACCAGCTGAG
	GGGGAACAAGAGCTCCAGGGCTCAGCGATGCACCCAGGTGCCAAGTGGTACCCTGGGTCTGTGAGGC
	GAGCCACCTTGGAGTTCGAAGAGCGCTTACGGCAGGAGCAAGAGCATCATGGTGCTGCCCCAACATG
	TACCTCATTGTCCACTCGTAAGAATTCAAAGAATGATTCTTCTGTGGCAGACCTAGCACCAAAAGGG
	AAAAGTGATGAAGCCCCCCCAGAACATTCATTTGTCCTCAAGGAACCAGAAATGAGCAAAGGCAAAG
	GGAAATACAGTGGGTCTGAGGCTGGCTCACTGTCCCATTCTGAGCAGAATGCCACTGTTCCAGCTCC
	CAGGGTGCTGGAGTTTGACCACTTGCCAGATCCTCAGGAGGGCCCAGGGTCAGATACTGGAACACAG
	CAGGAAGGAGTCCTGAAGGATCTGAGGACTGTGATTCCATACCACGAGTCTGAAACACAAGCAGTCC
	CTCTTCCCCTTCCCAAGAGGGTAGAAATCATTGAATATACCCACATAGTTACATCACCCAATCACAC
	TGGGCCAGGGAGTGAAATAGCCACCAGTGAGAAGACCGGAGAGCAAGGGCTGAGGAAAGTGAACATG
	GAAAAATCTGTCACTGTGCTCTGCACACTGGATGAAAATCTAAACAGGACTCTGGACCCCAACCAGG
	TTTCTCTGCACCCCCAAGTGCTACCTCTGCCTCATTCTTCCTCCCCTGAGCACAACAGACCCACTCA
	CCATCCAACCTCCATCCTGAGTAGCCCTGAAGACAGAGGCAGCAGCCTGTCCACAGCCCTGGAGACA
	GCAGCACCTTTTGTCAGTCATACAACCCATTTACTGTCTGCCAGTTTGGATTACCTGCATCCCCAGA
	CTATGGTTCACCTGGAGAGGGCTTCACAGAGCAGAGCAGCACTACAGATGAGCCCTCTGCAGCAGGT
	TAGCTGCGAAGAAAGTCAGGAGAGCCCTCTCTCCAGTGGCAGTGAGGTGCCATATAAGGACTCCCAG
	CTAAGTAGCGCAGACCTAAGTTTAATTAGCAAACTTCGTGACAACACTGGGCAGTTACAGGAGAAAA
	TGGACCCATTGCCTGTAGCCTGTCGACTCCCACATAGCTCTAGTAGTGAAACATAAAAGAGTCTCAG
	CCACAGCCCCCGTGTGGTGAAGGAGCGTGCTAAAGAAATCGAGTCTCGAGTGGTTTTCCAGGCAGGG
	CTCACCAAACCATCCCAAATGAGGCGCTCAGCTTCTCTCGCCAAATTAGGTTACTTGGACCTCTGTA
	AAGACTGCTTACCAGAGAGGGAGCCTGCCTCCTGTGAATCCCCTCATCTCAAACTGCTTCAGCCTTT
	CCTCAGAACAGACTCAGGCATGCACGCGATGGAGGACCAAGAGTCCCTAGAAAACCCAGGTGCCCCC
	CACAACCCAGAGCCCACCAAGTCTTTTGTAGAACAACTCACAACAACAGAGTGTATTGTGCAGAGCA
	AGCCAGTGGAGAGGCCCCTTGTGCAGTATGCCAAAGAATTTGGTTCTAGTCAGCAGTATTTGCTCCC
	CAGGGCAGGACTTGAATTGACTAGTTCTGAAGGAGGCCTTCCCGTGCTACAGACCCAGGGACTGCAG
	TGTGCATGCCCAGCTCCAGGGCTGGCCGTGGCACCCCGTCACCAACGGCCAGAAACTCACCCCCTTA
	GGAGACTGAAAAAGGCAAATGACAAAAAACGGACAACCAACCCCTTCTATAATACCATGTGATTCTG
	AGCCTACACATGTGACTTTCTAGAAGAAAATGTTTGTAAAGGGGCAGGTGTAATATGTAAGGAACAT
	GCACTTTATTGGTTAATTTTATAATATTTTGGTCATTTTACTGTTTCTGGTGCATGCAGGGTTTGGG
	TGTTTTTCAGTGTGTATGTGTGTGTATATGTAAGGGGAAAGAGAGATTGATCTGGATGGCAAGACCC
	TTTATCATTTTTTATTTAAAAAAATCAAACCTCAAAAAAGTCATTTTCAGAGAACACCTTTATCAAA
	GGCAATTGCTGTTTTTCAGTCAGCTGCCACCTGCTTCTCATTTTGCCCTCTGAGAAAAAGGCATGGT
	TTCTTAATTGAGGGAAGGAAGCAGATTCG
	ORF Start: ATG at 58		ORF Stop: TGA at 3544
	SEQ ID NO:120	1162 aa	MW at 128957.7 kD
NOV26a,	MMQKDLENITSKEIRTELEMQMVCNLREFKEFIDNEMIVILGQMDSPTQIFEHVFLGSEWNASNLED
CG140747-01
Protein Sequence	LQNRGVRYILNVTREIDNFFPGVFEYHNIRVYDEEATDLLAYWNDTYKFISKAKKHGSKCLVHCKMG
	VSRSASTVIAYAMKEYGWNLDRAYDYVKERRTVTKPNPSFMRQLEEYQGILLASKQRHNKLWRSHSD
	SDLSDHHEPICKPGLELNKKDITTSADQIAEVKTMESHPPIPPVFVEHMVPQDANQKGLCTKERMIC
	LEFTSREFHAGQIEDELNLNDINGCSSGCCLNESKFPLDNCHASKALIQPGHVPEMANKFPDLTVED
	LETDALKADMNVHLLPMEELTSPLKDPPMSPDPESPSPQPSCQTEISDFSTDRIDFFSALEKFVELS
	QETRSRSFSHSRMEELGGGRNESCRLSVVEVAPSKVTADDQRSSSLSNTPHASEESSMDEEQSKAIS
	ELVSPDIFMQSHSENAISVXEIVTEIESISQGVGQIQLKGDILPNPCHTPKKNSIHELLLERAQTPE
	NKPGHMEQDEDSCTAQPELAKDSGMCNPEGCLTTHSSIADLEEGEPAEGEQELQGSGMHPGAKWYPG
	SVRRATLEFEERLRQEQEHHGAAPTCTSLSTRKNSKNDSSVADLAPKGKSDEAPPEHSFVLKEPEMS
	KGKGKYSGSEAGSLSHSEQNATVPAPRVLEFDHLPDPQEGPGSDTGTQQEGVLKDLRTVIPYQESET
	QAVPLPLPKRVEIIEYTHTVTSPNHTGPGSEIATSEKSGEQGLRKVNMEKSVTVLCTLDENLNRTLD
	PNQVSLHPQVLPLPHSSSPEHNRPTDHPTSILSSPEDRGSSLSTALETAAPFVSHTTHLLSASLDYL
	HPQTMVHLEGFTEQSSTTDEPSAEQVSWEESQESPLSSGSEVPYKDSQLSSADLSLISKLGDNTGEL
	QEKMDPLPVACRLPHSSSSENIKSLSHSPGVVKERAKEIESRVVFQAGLTKPSQMRRSASLAKLGYL
	DLCKDCLPEREPASCESPHLKLLQPFLRTDSGMHAMEDQESLENPGAPHNPEPTKSFVEQLTTTECI
	VQSKPVERPLVQYAKEFGSSQQYLLPRAGLELTSSEGGLPVLQTQGLQCACPAPGLAVAPRQQHGRT
	HPLRRLKKANDKKRTTNPFYNTM

[0489] Further analysis of the NOV26a protein yielded the following properties shown in Table 26B.

TABLE 26B
Protein Sequence Properties NOV26a
PSort     0.4500 probability located in cytoplasm; 0.3000
analysis: 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:

[0490] 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
Geneseq	Protein/Organism/Length	Match	for the	Expect
Identifier	[Patent #, Date]	Residues	Matched Region	Value
AAE06776	Human dual-specificity	1 . . . 188	188/188 (100%)	e−107
	phosphatase (DSP)-13 splice	1 . . . 188	188/188 (100%)
	variant protein - Homo
	sapiens, 241 aa.
	[WO200157221-A2,
	09 AUG. 2001]
AAE06775	Human dual-specificity	1 . . . 188	188/188 (100%)	e−107
	phosphatase (DSP)-13	269 . . . 456	188/188 (100%)
	protein - Homo sapiens, 509
	aa. [WO200157221-A2,
	09 AUG. 2001]
AAE07044	Human dual-specificity	1 . . . 188	187/188 (99%)	e−106
	phosphatase (DSP)-13	269 . . . 456	187/188 (99%)
	mutant protein, D368A -
	Homo sapiens, 509 aa.
	[WO200157221-A2,
	09 AUG. 2001]
AAE07045	Human dual-specificity	1 . . . 188	187/188 (99%)	e−106
	phosphatase (DSP)-13	269 . . . 456	187/188 (99%)
	mutant protein, C399S -
	Homo sapiens, 509 aa.
	[WO200157221-A2,
	09 AUG. 2001]
AAE04835	Human SGP001 phosphatase	1 . . . 188	184/188 (97%)	e−102
	polypeptide - Homo sapiens,	262 . . . 445	184/188 (97%)
	498 aa. [WO200146394-A2,
	28 JUN. 2001]

[0491] 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
Protein		Residues/	Identities/
Accession		Match	Similarities for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
Q9C0D8	KIAA1725 protein - Homo	121 . . . 1162	1042/1042 (100%)	0.0
	sapiens (Human), 1042 aa	1 . . . 1042	1042/1042 (100%)
	(fragment).
Q8WYL2	HSSH-2 - Homo sapiens	1 . . . 187	187/187 (100%)	e−106
	(Human), 449 aa.	262 . . . 448	187/187 (100%)
BAC04546	CDNA FLJ38102 fis, clone	1 . . . 246	163/249 (65%)	7e−91
	D3OST2000618,	274 . . . 522	195/249 (77%)
	moderately similar to
	Drosophila melanogaster
	slingshot mRNA - Homo
	sapiens (Human), 703 aa.
Q8WYL4	HSSH-1S - Homo sapiens	1 . . . 246	163/249 (65%)	7e−91
	(Human), 692 aa.	263 . . . 511	195/249 (77%)
Q8WYL5	HSSH-1L - Homo sapiens	1 . . . 246	163/249 (65%)	7e−91
	(Human), 1049 aa.	263 . . . 511	195/249 (77%)

[0492] PFam analysis predicts that the NOV26a protein contains the domains shown in the Table 26E.

TABLE 26E
Domain Analysis of NOV26a
			Identities/
		NOV26a	Similarities
	Pfam	Match	for the	Expect
	Domain	Region	Matched Region	Value
	DSPc	46 . . . 184	62/172 (36%)	1.5e−45
			116/172 (67%)

Example 27

[0493] 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: 121	1290bp
NOV27a,	GACCTTAAGATTCCCCGCTCCAGCTCCGAGATGTCAGCAACGCTGATCCTGGAGCCCGCGGGCCGCG
CG141137-01
DNA Sequence	GCTGCCGAGACAAGCCGGTGCGCATCACCATGCGCGGCCTGGCTTCGGAGCCGCTGGACACGCTGCG
	CGCGTCCCTGCGCGGCGAGAAGGCTGGGCTCTTCCGCTACTGCGCCGACGCCCGCGGCGAGCTGGAC
	CTGGAGCGCGCGCCCGTGCTGGGCGGCAGCTTTAGGGGGCTAGAGTCCATGGGGCTGCTCTGGGCCC
	TGGAATCCAAGAAACCTTTTTGGCGCTTTCTGAAGCGGGACGTACAGATTCCCTTTATCGTGGAGTT
	GGAGGTGCTGGACGGCCACGACCCCGAGCCTGGAGAGCGCGACTTCCTCCCACAAGGGGTGCGGAGC
	GATTCGGTGCGCGCGGGCCGGGTACGCGCCACGCTCTTCCTGCCGCCAGGACCTGGACCCTTCCTAG
	GGATCATTGGCATCTTTGGTATTGGAGGGAGCCTGTTGGAATATCGAGCCAGCCTCCTTGCTGGCCA
	TGGCTTTGCCACGTTCGCTCTAGCTTGTTATAACTTTGAAGATCTCCCCAAGAACGTGGACAACATA
	CCCCTGGAGTACTTCGAAGAAGCCCTATGCTACATGCTTCAACATCCCCAGGTAAAAGGCCCAGGCA
	CTGGGCTTTGGGGCATTTCTCTAGGAGCTGATATTTGTCTCTCAATGGCCTCATTCTTGAAGAATGA
	CTCAGACACAGTTTCCATCAATGGATCCGGGATCAGTGGGAACAGAGGCATAAACTGTAAGCAGAAT
	AGCATTCCACCATTGGGCTATGACCTGAGGAGAATCAAGGTAGCTTTCTCAGGCCTCGTGGACGTCG
	TGGATATAAAGAATGATCTTGTAGGAGGGTATAAGAACCCCAGCATGATTTCAATGGAGAAGGCCCA
	GGGCCCCATCATTTTCATTGTTGGTCAGGATGACCATAACTGGAGGAGTGAGTTGTATGCCGAACGG
	TTACGGGCCCATGGAAAGGGAAAACCCCAGATCATCTGTTACCCTGGGACTGGGCTTTACACTGAGC
	CTCCTTACTTCCCCCTGTGCCCAGCTTCCCTTCACAAATTACTGAACAAACACGTGATATGGGTTGG
	GGAGCCAAGGGCTCATTCTAAGGCCCAGGTAGATGCCTGGAAGCAAATTCTAGCCGCCTTCTCCAAA
	CACCTGGGAGGTACCCAGAAAACAGCTTTCCCTAAATTGTAATGCCTTTGTCTGTTGTTGACATGAG
	AGAGTCAAGATCACATT
	ORF Start: ATG at 31	ORF Stop: TAA at 1246
	SEQ ID NO: 122	405 aa	MW at 44471.8kD
NOV27a,	MSATLILEPAGRGCRDKPVRITNRGLASEPLDTLRASLRGEKAGLFRYCADARGELDLERAPVLGGS
CG141137-01
Protein Sequence	FRGLESMGLLWALESKKPFWRFLKRDVQIPFIVELEVLDGHDPEPGERDFLPQGVRSDSVPAGRVRA
	TLFLPPGPGPFLGIIGIFGIGGSLLEYRASLLAGHGFATFALACYNFEDLPKNVDNIPLEYFEEALC
	YMLQHPQVKGPGTGLWGISLGADICLSMASFLKNDSDTVSINGSGISGNRGINCKQNSIPPLGYDLR
	RIKVAFSGLVDVVDIKNDLVGGYKNPSMISMEKAQGPIIFIVGQDDHNWRSELYAERLRAHGKEKPQ
	IICYPGTGLYTEPPYFPLCPASLHKLLNXMVINVGEPRAHSKAQVDAWKQILAAFCKHLGGTQKTAF
	PKL

[0494] 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; 0.3164
analysis: probability located in microbody (peroxisome);
          0.1984 probability located in lysosome (lumen);
          0.1000 probability located in mitochondrial
          matrix space
SignalP   No Known Signal Sequence Predicted
analysis:

[0495] 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
AAU76350	Human Acyl-CoA	1 . . . 405	347/421 (82%)	0.0
	thioesterase 56939 - Homo	1 . . . 421	361/421 (85%)
	sapiens, 421 aa.
	[WO200208274-A2,
	31 JAN. 2002]
AAM41490	Human polypeptide SEQ ID	1 . . . 400	256/416 (61%)	e−141
	NO 6421 - Homo sapiens,	74 . . . 489	299/416 (71%)
	494 aa. [WO200153312-A1,
	26 JUL. 2001]
AAM39704	Human polypeptide SEQ ID	1 . . . 400	256/416 (61%)	e−141
	NO 2849 - Homo sapiens,	63 . . . 478	299/416 (71%)
	483 aa. [WO200153312-A1,
	26 JUL. 2001]
AAY71112	Human Hydrolase protein-10	1 . . . 400	256/416 (61%)	e−141
	(HYDRL-10) - Homo	63 . . . 478	299/416 (71%)
	sapiens, 483 aa.
	[WO200028045-A2,
	18 MAY 2000]
AAB93479	Human protein sequence	1 . . . 400	255/416 (61%)	e−141
	SEQ ID NO: 12766 - Homo	63 . . . 478	298/416 (71%)
	sapiens, 483 aa.
	[EP1074617-A2,
	07 FEB. 2001]

[0496] 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
BAC04313	CDNA FLJ36904 fis, clone	1 . . . 405	345/421 (81%)	0.0
	BRACE2002762, moderately	1 . . . 421	359/421 (84%)
	similar to CYTOSOLIC
	ACYL COENZYME A
	THIOESTER HYDROLASE,
	INDUCEBLE (EC 3.1.2.2) -
	Homo sapiens(Human), 421
	aa.
Q9QYR8	Peroxisomal long chain	1 . . . 405	275/421 (65%)	e−158
	acyl-CoA thioesterase Ib -	1 . . . 421	327/421 (77%)
	Mus musculus (Mouse), 421
	aa.
P49753	Peroxisomal acyl-coenzyme	1 . . . 400	256/416 (61%)	e−141
	A thioester hydrolase 2 (EC	1 . . . 416	299/416 (71%)
	3.1.2.2) (Peroxisomal
	long-chain acyl-coA
	thioesterase 2) (ZAP128) -
	Homo sapiens (Human), 421
	aa.
Q9QYR7	Peroxisomal acyl-coenzyme	1 . . . 405	245/423 (57%)	e−130
	A thioester hydrolase 2 (EC	12 . . . 432	296/423 (69%)
	3.1.2.2) (Peroxisomal
	long-chain acyl-coA
	thioesterase 2) (PTE-Ia) -
	Mus musculus (Mouse), 432
	aa.
O88267	Cytosolic acyl coenzyme A	1 . . . 405	239/422 (56%)	e−128
	thioester hydrolase, inducible	1 . . . 419	295/422 (69%)
	(EC 3.1.2.2) (Long chain
	acyl-CoA thioester
	hydrolase) (Long chain
	acyl-CoA hydrolase) (CTE-I)
	(LACH2) (ACH2) - Rattus
	norvegicus (Rat), 419 aa.

[0497] PFam analysis predicts that the NOV27a protein contains the domains shown in the Table 27E.

TABLE 27E
Domain Analysis of NOV27a
		Identities/
	NOV27a	Similarities
Pfam	Match	for the Matched	Expect
Domain	Region	Region	Value
No Significant Matches Found to Publically Available Domains

Example 28

[0498] 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: 123	384 bp
NOV28a,	TTGTGCAACGGCAGTCCAGCCCGGGCAAAAGAGTGAGACTATGTCTCTAAAAAAACCAAGATGGAGT
CG141240-01
DNA Sequence	CAGTTGTACCAGTGAAGGACAAGAAACTTCTGGAGGTCAAACTAGGGGAGCTGCCAAGCTGGATCTT
	GATGTGCGACTTCAGCCCTAGTGGCCTTGATGGAGCGTTTCAAAGAGGTTACTACTGGTACTACAAC
	AAGTACATCAACGTCAAGAAGGGGAGCATCTCGGGGTTTACCATGGTGCTGGCAGGGTACATGCTCT
	TCATCTACTGCCTTTCCTACAAGAGCTCAAGCACGAGCGGCTATGCAAGTACCACTGAAGAAGACA
	TGCTCTGCACTCCCCCAGCAACCTTCTTGGCTGCAACCCCTCCATAAGC
	ORF Start: ATG at 61	ORF Stop: TGA at 325
	SEQ ID NO: 124	88 aa	MW at 10416.2kD
NOV28a,	MESVVPVKDKKLLEVKLGELPSWILMWDFSPSGLDGAFQRGYYWYYNKYINVKKGSISGFTMVLAGY
CG141240-01
Protein Sequence	MLFIYCLSYKELKHERLCKYH

[0499] Further analysis of the NOV28a protein yielded the following properties shown in Table 28B.

TABLE 28B
Protein Sequence Properties NOV28a
PSort     0.6400 probability located in microbody
analysis: (peroxisome); 0.4500 probability located
          in cytoplasm; 0.1000 probability located
          in mitochondrial matrix space; 0.1000
          probability located in lysosome (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0500] A search of the NOV28a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 28C.

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
AAG89150	Human secreted protein, SEQ	1 . . . 88	75/88 (85%)	4e−37
	ID NO: 270 - Homo sapiens,	1 . . . 88	77/88 (87%)
	88 aa. [WO200142451-A2,
	14 JUN. 2001]
AAY66171	Human bladder tumour EST	1 . . . 88	75/88 (85%)	4e−37
	encoded protein 29 - Homo	17 . . . 104	77/88 (87%)
	sapiens, 104 aa.
	[DE19818619-A1,
	28 OCT. 1999]
AAB65990	Human secreted protein	3 . . . 88	74/86 (86%)	1e−36
	BLAST search protein SEQ	2 . . . 87	76/86 (88%)
	ID NO: 130 - Homo sapiens,
	87 aa. [WO200077023-A1,
	21 DEC. 2000]
AAB65989	Human secreted protein	3 . . . 88	74/86 (86%)	1e−36
	BLAST search protein SEQ	2 . . . 87	76/86 (88%)
	ID NO: 129 - Homo sapiens,
	87 aa. [WO200077023-A1,
	21 DEC. 2000]
AAY29462	Human CBMAJC02 protein -	5 . . . 88	72/84 (85%)	1e−35
	Homo sapiens, 94 aa.	11 . . . 94	74/84 (87%)
	[WO9936526-A1,
	22 JUL. 1999]

[0501] In a BLAST search of public sequence datbases, 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
A54211	H+-transporting ATP synthase	1 . . . 88	69/88 (78%)	3e−35
	(EC 3.6.1.34) chain f - bovine, 88	1 . . . 88	77/88 (87%)
	aa.
P56134	ATP synthase f chain,	5 . . . 88	72/84 (85%)	3e−35
	mitochondrial (EC 3.6.3.14) -	10 . . . 93	74/84 (87%)
	Homo sapiens (Human), 93 aa.
Q28851	ATP synthase f chain,	3 . . . 88	68/86 (79%)	8e−35
	mitochondrial (EC 3.6.3.14) -	2 . . . 87	76/86 (88%)
	Bos taurus (Bovine), 87 aa.
Q95339	ATP synthase f chain,	3 . . . 88	66/86 (76%)	4e−34
	mitochondrial (EC 3.6.3.14) -	2 . . . 87	76/86 (87%)
	Sus scrofa (Pig), 87 aa.
AAH29226	ATP synthase, H+ transporting,	1 . . . 88	65/88 (73%)	1e−33
	mitochondrial F0 complex,	1 . . . 88	78/88 (87%)
	subunit f, isoform 2 - Mus
	musculus (Mouse), 88 aa.

[0502] PFam analysis predicts that the NOV28a protein contains the domains shown in the Table 28E.

TABLE 28E
Domain Analysis of NOV28a
		Identities/
	NOV28a	Similarities
Pfam	Match	for the Matched	Expect
Domain	Region	Region	Value
No Significant Matches Found to Publically Available Domains

Example 29

[0503] 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: 125	789 bp
NOV29a,	GGCCGTTCCTGCGCTCTCCTTCGCCTGCGGGCCGGCACTGCTCACCTCTCGTCCAGGGACATGACGG
CG141355-01
DNA Sequence	GCACGCCAGGCGCCGTTGCCACCCGGGATGGCGAGGCCCCCGAGCGCTCCCCGCCCTGCAGTCCGAG
	CTACGACCTCACGGGCAAGGTGATGCTTCTGGGAGACACAGGCGTCGGCAAAACATGTTTCCTGATC
	CAATTCAAAGACGGGGCCTTCCTGTCCGGAACCTTCATAGCCACCGTCGGCATAGACTTCAGGAACA
	AGGTGGTGACTCTCGATGGCGTGAGAGTGAAGCTGCAGATCTGGGACACCGCTGGGCAGGAACGGTT
	CCGAAGCGTCACCCATGCTTATTACAGAGATGCTCAGGCCTTGCTTCTGCTGTATGACATC~CCAAC
	AAATCTTCTTTCGACAACATCAGGGCCTGGCTCACTGAGATTCATGAGTATGCCCAGAGGGACGTGG
	TGATCATGCTGCTAGGCAACAAGGCGGATATGAGCAGCGAAAGAGTGATCCGTTCCGAAGACGGAGA
	GACCTTGGCCAGGGAGTACGGTGTTCCCTTCCTGGAGACCAGCGCCAAGACTGGCATGAATGTGGAG
	TTAGCCTTTCTGGCCATCGCCAAGGAACTGAAATACCGGGCCGGGCATCAGGCGGATGAGCCCAGCT
	TCCAGATCCCAGACTATGTAGAGTCCCAGAAGAAGCGCTCCAGCTGCTGCTCCTTCATGTGAATCCC
	AGGGGGCAGAGAGGAGGCTCTGGAGGCACACAGGATGCAGCCTTCCCCCTCC
	ORF Start: ATG at 61	ORF Stop: TGA at 730
	SEQ ID NO: 126	223aa	MW at 248 14.9kD
NOV29a,	MTGTPGAVATRDGEAPERSPPCSPSYDLTGKVMLLGDTGVGKTCFLIQFKDGAFLSGTFIATVGIDF
CG141355-01
Protein Sequence	RNKVVTVDGVRVKLQIWDTAGQERFRSVTHAYYRDAQALLLLYDITNXSSFDNIRAWLTEIHEYAQR
	DVVIMLLGNKADMSSERVIRSEDGETLAREYGVPFLETSAKTGMNVELAFLAIAKELKYRAGHQADE
	PSFQIRDYVESQKKRSSCCSFM
	SEQ ID NO: 127	686 bp
NOV29b,	TCCAGGAACATGACGGGCACGCCAGGCGCCGTTGCCACCCGGGATCGCGAGGCCCCCGAGCGCTCCC
CG141355-02
DNA Sequence	CGCCCTGCAGTCCGAGCTACGACCTCACGGGCAAGGTGATGCTTCTGGGAGACACAGGCGTCGGCAA
	AACATGTTTCCTGATCCAATTCAAAGACGGGGCCTTCCTGTCCGGAACCTTCATAGCCACCGTCGGC
	ATAGACTTCAGGAACAAGGTGGTGACTGTGGATGGCGTGAGAGTGAAGCTGCAGATCTGGGACACCG
	CTGGGCAGGAACGGTTCCGAAGCGTCACCCATGCTTATTACAGAGATGCTCAGGCCTTGCTTCTGCT
	GTATGACATCACCAACAAATCTTCTTTCGACAACATCAGGGCCTGGCTCACTGAGATTCATGAGTAT
	GCCCAGAGGGACGTGGTGATCATGCTGCTAGGCAACAAGGCGGATATGAGCAGCGAAAGAGTGATCC
	GTTCCGAAGACGGAGAGACCTTGGCCAGGGAGTACGGTGTTCCCTTCCTGGAGACCAGCGCCAAGAC
	TGGCATGAATGTGGAGTTAGCCTTTCTGGCCATCGCCAAGGAACTGAAATACCGCGCCCGOCATCAG
	GCGGATGAGCCCAGCTTCCAGATCCGAGACTATGTAGAGTCCCAGAAGAAGCGCTCCAGCTGCTGCT
	CCTTCATGTGAATCCC
	ORF Start: ATG at 10	ORF Stop: TGA at 679
	SEQ ID NO: 128	223 aa	MW at 24814.9kD
NOV29b,	MTGTPGAVATRDGEAPERSPPCSPSYDLTGKVMLLGDTGVGKTCFLTQFKDGAFLSGTFIATVGIDF
CG141355-02
Protein Sequence	RNRVVTVDGVRVKLQIWDTAGQERFRSVTHAYYRDAQALLLLYDITNKSSFDNIRAWLTEIHEYAQR
	DVVIMLLGNKADMSSERVIRSEDGETLAREYGVPFLETSAKTGMNVELAFLAIAKELKYRAGHQADE
	PSFQIRDYVESQKKRSSCCSFM

[0504] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 29B.

TABLE 29B
Comparison of NOV29a against NOV29b.
			Identities/Similarities
	Protein	NOV29a Residues/	for the
	Sequence	Match Residues	Matched Region
	NOV29b	1 . . . 223	223/223 (100%)
		1 . . . 223	223/223 (100%)

[0505] Further analysis of the NOV29a protein yielded the following properties shown in Table 29C.

TABLE 29C
Protein Sequence Properties NOV29a
PSort     0.4500 probability located in cytoplasm; 0.3020
analysis: probabilitylocated in microbody (peroxisome);
          0.1000 probability locatedin mitochondrial matrix
          space; 0.1000 probability located in
          lysosome (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0506] A search of the NOV29a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 29D.

TABLE 29D
Geneseq Results for NOV29a
		NOV29a	Identities/
		Residues/	Similarities
Geneseq	Protein/Organism/Length	Match	for the	Expect
Identifier	[Patent#, Date]	Residues	Matched Region	Value
AAM41696	Human polypeptide SEQ ID	1 . . . 223	223/223 (100%)	e−127
	NO 6627 - Homo sapiens,	10 . . . 232	223/223 (100%)
	232 aa. [WO200153312-A1,
	26 JUL. 2001]
AAU17119	Novel signal transduction	1 . . . 223	222/223 (99%)	e−126
	pathway protein, Seq ID 684 -	4 . . . 226	222/223 (99%)
	Homo sapiens,226 aa.
	[WO200154733-A1,
	02 AUG.2001]
AAU17541	Novel signal transduction	2 . . . 223	220/222 (99%)	e−125
	pathway protein, Seq ID 1106 -	1 . . . 222	220/222 (99%)
	Homo sapiens,222 aa.
	[WO200154733-A1,
	02 AUG.2001]
AAM39910	Human polypeptide SEQ ID	33 . . . 223	191/191 (100%)	e−106
	NO 3055 - Homo sapiens,	1 . . . 191	191/191 (100%)
	191 aa. [WO200153312-A1,
	26 JUL. 2001]
AAG67156	Amino acid sequence of	33 . . . 223	191/191 (100%)	e−106
	human 32712 G-protein -	1 . . . 191	191/191 (100%)
	Homo sapiens, 191 aa.
	[W0200164887-A2,
	07 SEP. 2001]

[0507] In a BLAST search of public sequence datbases, the NOV29a protein was found to have homology to the proteins shown in the BLASTP data in Table 29E.

TABLE 29E
Public BLASTP Results for NOV29a
		NOV29a	Identities/
Protein		Residues/	Similarities
Accession		Match	for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
Q96AX2	Ras-related protein Rab-37 -	1 . . . 223	223/223 (100%)	e−126
	Homo sapiens (Human),	1 . . . 223	223/223 (100%)
	223 aa.
Q9JKM7	Ras-related protein Rab-37 -	1 . . . 223	209/223 (93%)	e−118
	Mus musculus (Mouse), 223 aa.	1 . . . 223	215/223 (95%)
CAC88255	Sequence 13 from Patent	33 . . . 223	191/191 (100%)	e−106
	WO0164887 -	1 . . . 191	191/191 (100%)
	Homo sapiens (Human),
	191 aa.
Q9ULW5	Ras-related protein Rab-26 -	33 . . . 220	138/188 (73%)	9e−80
	Homo sapiens (Human),	1 . . . 188	166/188 (87%)
	190 aa.
P51156	Ras-related protein Rab-26 -	33 . . . 220	138/188 (73%)	8e−79
	Rattus norvegicus (Rat),	1 . . . 188	165/188 (87%)
	190 aa.

[0508] PFam analysis predicts that the NOV29a protein contains the domains shown in the Table 29F.

TABLE 29F
Domain Analysis of NOV29a
			Identities/
			Similarities
	Pfam	NOV29a Match	for the	Expect
	Domain	Region	Matched Region	Value
	arf	21 . . . 194	42/197 (21%)	1.9e−05
			104/197 (53%)
	ras	31 . . . 223	93/206 (45%)	6.2e−89
			164/206 (80%)

Example 30

[0509] 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: 129	1078 bp
NOV30a,	CAGATCCTCATTTCTTTTCCCTTCCTAGGTTTTAAAACATGAATCCTACACTCATCCTTGCTGCCTT
CG142072-01
DNA Sequence	TTGCCTGGGAATTGCCTCAGCTACTCTAACATTTGATCACAGTTTAGAGGCACAGTGGACCAAGTGG
	AAGGCGATGCACAACAGATTATACGGCATGAATGAAGAAGGATGGAGGAGAGCAGTGTGCGAGAAGA
	ACATGAAGATGATTGAACTGCACAATCAGGAATACACGGAAGGGAAACACAGCTTCACAATGGCCAT
	GAACGCCTTTGGAGACATGACCAGTGAAGAATTCAGGCAGGTGATGAATGGCTTTCAAAACCGTAAG
	CCCACGAAGGGGAAAGTGTTCCAGGAACCTCTGTTTTATGAGGCCCCCAGATCTGTGGATTGGAGAG
	AGAAACGCTACGTGACTCCTGTGAAGAATCAGGGTCAGTGTGGTTCTTGTTGGGCTTTTAGTGCTAC
	TGGTGCTCTTGAAGGACAGATGTTCCGGAAAACTCGGAGGCTTATCTCACTGAGTGAGCAGAATCTG
	GTAGACTGCTCTGGGCCTCAAGGCAATGAAGGCTCCAATGGTGGCCTAATGGATTATGCTTTCCAGT
	ATGTTCAGGATAATGGAGGCCTGGACTCTGAGGAATCCTATCCATATGAGGCAACAGAAGAATCCTG
	TAAGTACAATCCCAAGTACTCTGTTGCTAATGACACCGGCTTTGTGGACATCCCTAAGCAGGAGAAG
	GCCCTGATGAAGGCAGTTGCAACTGTGGGGCCCATTTCTGTTGCTATTGATGCAGGTCATGAGTCCT
	TCCTGTTCTATAAAGAAGGCATTTATTTTGAGCCAGACTGTAGCAGTGAAGACATGGATCATGGTGT
	GCTGGTGGTTGGCTACGGATTTGAAAGCACAGAATCAGATAACAATAAATATTGGCTGGTGAAGAAC
	AGCTGGGGTGAAGAATGGGGCATGGGTGGCTACGTAAAGATGGCCAAAGACCGGAGAAACCATTGTG
	GAATTGCCTCAGCAGCCAGCTACCCCACTGTGTGAGCTGGTGGACGGTGATGAGGAAGGACTTGACT
	GGGGAT
	ORF Start: ATO at 39	ORF Stop: TGA at 1038
	SEQ ID NO: 130	333 aa	MW at 37563.9kD
NOV3Oa,	MNPTLILAAFCLGIASATLTFDHSLEAQWTKWKAMHNRLYGMNEEGWRRAVWEKNMKMIELHNQEYR
CG142072-01
Protein Sequence	EGKHSFTNAHNAFGDMTSEEFRQVMNGFQNRKPRKGKVFQEPLFYEAPRSVDWREKGYVTPVKNQGQ
	CGSCWAFSATGALEGQMFRKTGRLTSLSEQNLVDCSGPQGNEGCNGGLMDYAFQYVQDNGGLDSEES
	YPYEATEESCKYNPKYSVANDTGFVDIPKQEKALMKAVATVGFISVAIDAGHESFLFYKEGIYFEPD
	CSSEDMDHGVLVVGYGPESTESDNNKYWLVKNSWGEEWGMGGYVKMAKDRRNHCGIASAASYPTV
	SEQ ID NO: 131	870 bp
NOV3Ob,	CCTGGGAATTGCCTCAGCTACTCTAACATTTGATCACAGTTTAGAGGCACAGTGGACCGAGTGGAAG
CG142072-02
DNA Sequence	GCGATGCACAACAGATTATACGGCATGAATGAAGAAGGATGGAGGAGAGCAGTGTGGGAGAAGAACA
	TGAAGATGATTGAACTGCACAATCAGGAATACAGGGAAGGGAAACACAGCTTCACAATGGCCATGAA
	CGCCTTTGGAGACATCACCAGTGAAGAATTCAGGCAGGTGATGAATGGCTTTCAAAACCGTAAGCCC
	AGGAAGGGGAAAGTGTTCCGGAAAACTGGGAGGCTTATCTCACTGAGTGAGCAGAATCTGGTAGACT
	GCTCTGGGCCTCAAGGCAATGAAGGCTGCAATGGTGGCCTAATGGATTATGCTTTCCAGTATGTTCA
	GGATAATGGAGGCCTGGACTCTGAGGAATCCTATCCATATGAGGCAACAGAAGAATCCTGTAAGTAC
	AATCCCAAGTATTCTGTTGCTAATGACACCGGCTTTGTGGACATCCCTAAGCACGAGAAGGCCCTGA
	TGAAGGCAGTTGCAACTGTGGGGCCCATTTCTGTTGCTATTGATGCAGGTCATGAGTCCTTCCTGTT
	CTATAAAGAAGGCATTTATTTTGAGCCAGACTGTAGCAGTGAAGACATGGATCATGGTGTGCTGGTG
	GTTGGCTACGGATTTGAAAGCACAGAATCAGATAACAATAAATATTGGCTGGTGAAGAACAGCTGGG
	GTGAAGAATGCGGCATGGGTGGCTACGTAAAGATGGCCAAAGACCGGAGAAACCATTGTGGAATTGC
	CTCAGCAGCCAGCTACCCCACTGTGTGAGCTGGTGGACGGTCATGAGGAAGGACTTGACTGGGGAT
	ORF Start: at 2	ORF Stop: TGA at 830
	SEQ ID NO: 132	1276 aa	MW at 31236.6kD
NOV30b,	LGIASATLTFDHSLEAQWTEWKAMHNRLYGMNEEGWRRAVWEKNMKMIELHNQEYREGKHSFTMAMN
CG142072-02
Protein Sequence	AFGDMTSEEFRQVMNGFQNRKPRKGKVFRKTGRLISLSEQNLVDCSGPQGNEGCNGGLMDYAFQYVQ
	DNGGLDSEESYPYEATEESCKYNPKYSVANDTGFVDIPKQEKALMKAVATVGPISVAIDAGHESFLF
	YKECIYFEPDCSSEDMDHGVLVVCYGFESTESDNNXYWLVKNSWGEEWGMGGYVKNAXDRRNHCGIA
	SAASYPTV

[0510] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 30B.

TABLE 30B
Comparison of NOV30a against NOV30b.
			Identities/
			Similarities
		NOV30a Residues/	for the
	Protein Sequence	Match Residues	Matched Region
	NOV30b	12 . . . 333	275/322 (85%)
		1 . . . 276	276/322 (85%)

[0511] Further analysis of the NOV30a protein yielded the following properties shown in Table 30C.

TABLE 30C
Protein Sequence Properties NOV30a
PSort     0.8200 probability located in outside; 0.1679 probability
analysis: located inmicrobody (peroxisome); 0.1000 probability
          located in endoplasmic reticulum(membrane); 0.1000
          probability located in endoplasmic reticulum (lumen)
SignalP   Cleavage site between residues 18 and 19
analysis:

[0512] 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 30D.

TABLE 30D
Geneseq Results for NOV30a
		NOV30a	Identities/
		Residues/	Similarities
Geneseq	Protein/Organism/Length	Match	for the	Expect
Identifier	[Patent #, Date]	Residues	Matched Matched Region	Value
ABB77396	Human cathepsin L - Homo	1 . . . 333	333/333 (100%)	0.0
	sapiens, 333 aa.	1 . . . 333	333/333 (100%)
	[DE10050274-A1,
	18 APR. 2002]
AAW47031	Human procathepsin L - Homo	1 . . . 333	333/333 (100%)	0.0
	sapiens, 333 aa.	1 . . . 333	333/333 (100%)
	[US5710014-A,
	20 JAN.1998]
AAM93531	Human polypeptide, SEQ	1 . . . 333	332/333 (99%)	0.0
	ID NO: 3271 - Homo	1 . . . 333	332/333 (99%)
	sapiens, 333 aa.
	[EP1130094-A2,
	05 SEP. 2001]
AAR28829	Human procathepsin L -	1 . . . 333	332/333 (99%)	0.0
	Homo sapiens,	1 . . . 333	332/333 (99%)
	333 aa. [WO9219756-A,
	12 NOV.1992]
AAP82094	pHu-16 sequence encoded	1 . . . 333	327/333 (98%)	0.0
	human procathepsin L -	1 . . . 333	332/333 (99%)
	Homo sapiens, 333 aa.
	[USN7154692-N,
	11 FEB. 1988]

[0513] 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 30E.

TABLE 30E
Public BLASTP Results for NOV30a
		NOV30a	Identities/
Protein		Residues/	Similarities
Accession		Match	for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
P07711	Cathepsin L precursor	1 . . . 333	333/333 (100%)	0.0
	(EC 3.4.22.15)(Major	1 . . . 333	333/333 (100%)
	excreted protein) (MEP) - Homo
	sapiens (Human), 333 aa.
Q9GKL8	Cysteine protease -	1 . . . 333	320/333 (96%)	0.0
	Cercopithecus aethiops	1 . . . 333	328/333 (98%)
	(Green monkey) (Grivet),
	333 aa.
Q9GL24	Cathepsin L (EC 3.4.22.15) -	1 . . . 333	270/334 (80%)	e−166
	Canis familiaris (Dog),	1 . . . 333	299/334 (88%)
	333 aa.
Q28944	Cathepsin L precursor	1 . . . 333	263/334 (78%)	e−162
	(EC 3.4.22.15) -	1 . . . 334	293/334 (86%)
	Sus scrofa (Pig), 334 aa.
P25975	Cathepsin L precursor	1 . . . 333	257/334 (76%)	e−160
	(EC 3.4.22.15)-	1 . . . 334	291/334 (86%)
	Bos taurus (Bovine), 334 aa.

[0514] PFam analysis predicts that the NOV30a protein contains the domains shown in the Table 30F.

TABLE 30F
Domain Analysis of NOV30a
		Identities/
	NOV30a	Similarities
	Match	for the	Expect
Pfam Domain	Region	Matched Region	Value
Peptidase_C1	114 . . . 332	129/337 (38%)	1.8e−132
		201/337 (60%)

Example 31

[0515] The NOV31 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 31A.

TABLE 31A
NOV31 Sequence Analysis
	SEQ ID NO: 133	639 bp
NOV31 a,	CCTGTTTAATAAACAGATCTTGGCTTTGCAGATGCTGCCAGGAACCCCATACTATCAGCCATGGTCA
CG142102-01
DNA Sequence	ACCCCACCGTGTTCTTCAACATGGCTGTCAATGATGAGCCCTTGTGCCACGTCTCCTTTGAGCTGTA
	TGCAGACAAGTTTCCAAAGACAGCAGAAAACTTTCGTCCTCTGAGCACTGGAOAGAAAGGATTTCGT
	TACAAGGGTTTCTGCTTTTACAGAATTATTCCAGGOTTTATGTGGTTTATGTGTCAGGGCAGTGACT
	TCACACACCATAATGGCACTGGTGGCAAGTCCATCTATGGAGAGAAATTTGATGACGAGAACTTCAT
	CCTGAAGCATACAGGTCCTGAACCCTCACATTCCCAAACCAATTACTTATCCATGGCAAATGCTGGA
	CCCAACACAAATGGTTCCCAGTTTTTCCTCTGCACTGCCAAGACTGAGTGGTTGGATGGCACACATG
	TGGTCTTTGGCAAGGTGAAAGAAGGCATCAATATTGTGGAGGCCATGGAGCGCTTTGGATCTAGGAA
	TGGCAAGACCAGcAGATCACCATTGTTGACTGTGGACAACTCTAATGAATTTAACTTGTGTTTTTT
	CTTTTTAAGATGGAGTTTCACTCTTGTTTCCCAGGC
	ORF Start: ATG at 61	ORF Stop: TAA at 580
	SEQ ID NO: 134	173 aa	MW at 19324.7kD
NOV31 a,	MVNPTVFFNMAVNDEPLCHVSFELYADKFPKTAENFRALSTGEKGFGYKGFCFYRIIPGFMWFMCQG
CG142102-01
Protein Sequence	SDFTHHNGTGGKSIYGEKFDDENFILKHTGPEPSHSQTNYLSHANAGPNTNGSQFFLCTAKTEWLDG
	THVVFGKVKEGINIVEAMERFGSRNGKTSKITIVDCGQL

[0516] Further analysis of the NOV31a protein yielded the following properties shown in Table 31B.

TABLE 31B
Protein Sequence Properties NOV31a
PSort     0.6400 probability located in microbody (peroxisome); 0.6000
analysis: probability located in plasma membrane; 0.4500 probability
          located in cytoplasm; 0.1000 probability located in
          mitochondrial matrix space
SignalP   No Known Signal Sequence Predicted
analysis:

[0517] A search of the NOV31 a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 31C.

TABLE 31C
Geneseq Results for NOV31a
		NOV31a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAU01195	Human cyclophilin A	1 . . . 173	144/174 (82%)	2e−78
	protein - Homo sapiens, 165	1 . . . 164	152/174 (86%)
	aa. [WO200132876-A2,
	10 MAY 2001]
AAW56028	Calcineurin protein -	1 . . . 173	144/174 (82%)	2e−78
	Mammalia, 165 aa.	1 . . . 164	152/174 (86%)
	[WO9808956-A2,
	05 MAR. 1998]
AAG03831	Human secreted protein, SEQ	1 . . . 173	144/174 (82%)	3e−78
	ID NO: 7912 - Homo	1 . . . 164	152/174 (86%)
	sapiens, 165 aa.
	[EP1033401-A2,
	06 SEP. 2000]
AAR13726	Bovine cyclophilin - Bos	2 . . . 173	143/173 (82%)	4e−78
	taurus, 163 aa.	1 . . . 163	151/173 (86%)
	[US5047512-A,
	10 SEP. 1991]
AAG65275	Haematopoietic stem cell	2 . . . 173	143/173 (82%)	7e−78
	proliferation agent related	1 . . . 163	151/173 (86%)
	human protein #2 - Homo
	sapiens, 164 aa.
	[JP2001163798-A,
	19 JUN. 2001]

[0518] 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 31D.

TABLE 31D
Public BLASTP Results for NOV31a
		NOV31a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
CAC39529	Sequence 26 from Patent	1 . . . 173	144/174 (82%)	5e−78
	WO0132876 - Homo sapiens	1 . . . 164	152/174 (86%)
	(Human), 165 aa.
P04374	Peptidyl-prolyl cis-trans	2 . . . 173	143/173 (82%)	1e−77
	isomerase A (EC 5.2.1.8)	1 . . . 163	151/173 (86%)
	(PPIase) (Rotamase)
	(Cyclophilin A) (Cyclosporin
	A-binding protein) - Bos
	taurus (Bovine), and, 163 aa.
Q9BRU4	Peptidylprolyl isomerase A	1 . . . 173	143/174 (82%)	2e−77
	(cyclophilin A) - Homo	1 . . . 164	151/174 (86%)
	sapiens (Human), 165 aa.
P05092	Peptidyl-prolyl cis-trans	2 . . . 173	143/173 (82%)	2e−77
	isomerase A (EC 5.2.1.8)	1 . . . 163	151/173 (86%)
	(PPIase) (Rotamase)
	(Cyclophilin A) (Cyclosporin
	A-binding protein) - Homo
	sapiens (Human),, 164 aa.
Q96IX3	Peptidylprolyl isomerase A	1 . . . 173	143/174 (82%)	6e−77
	(cyclophilin A) - Homo	1 . . . 164	151/174 (86%)
	sapiens (Human), 165 aa.

[0519] PFam analysis predicts that the NOV31a protein contains the domains shown in the Table 31E.

TABLE 31E
Domain Analysis of NOV31a
			Identities/
		NOV31a	Similarities for
	Pfam	Match	the Matched	Expect
	Domain	Region	Region	Value
	pro_isomerase	5 . . . 173	101/187 (54%)	2.7e−84
			147/187 (79%)

Example 32

[0520] 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:135	651 bp
NOV32a,	CTTCCCTACCCTCCTCTCTCCCACACCACTGGCACCAGGCCCCGGACACCCGCTCTGCTGCAGGAGA
CG57760-01
DNA Sequence	ATGGCTACTCATCACACGCTGTGGATGGGACTGGCCCTGCTGGGGGTGCTGGGCGACCTGCAGGCAG
	CACCGGAGGCCCAGGTCTCCGTGCAGCCCAACTTCCAGCAGGACAAGTTCCTGGGGCGCTGGTTCAG
	CGCGGGCCTCGCCTCCAACTCGAGCTGGCTCCGGGAGAAGAAGGCGGCGTTGTCCATGTGCAAGTCT
	GTGGTGGCCCCTGCCACGGATGGTGGCCTCAACCTGACCTCCACCTTCCTCAGGAAAAACCAGTGTG
	AGACCCGAACCATGCTGCTGCAGCCCGCGGGGTCCCTCGGCTCCTACAGCTACCCGAGTCCCCACTG
	GGGCAGCACCTACTCCGTGTCAGTGGTGGAGACCGACTACGACCAGTACGCGCTGCTGTACAGCCAG
	GGCAGCAAGGGCCCTGGCGAGGACTTCCGCATGGCCACCCTCTACAGCCGAACCCAGACCCCCAGGG
	CTGAGTTAAAGGAGAAATTCACCGCCTTCTGCAAGGCCCAGGGCTTCACAGAGGATACCATTGTCTT
	CCTGCCCCAAACCGATAAGTGCATGACGGAACAATAGAAGGGCGAATT
	ORf Start: ATG at 68	ORF Stop: TAG at 638
	SEQ ID NO: 136	190 aa	MW at 21028.6kD
NOV32a,	MATHHTLWMGLALLGVLGDLQAAPEAQVSVQPNFQQDKFLGRWFSAGLASNSSWLREKKAALSMCKS
CG57760-01
Protein Sequence	VVAPATDGGLNLTSTFLRKNQCETRTMLLQPAGSLGSYSYRSPHWGSTYSVSVVETDYDQYALLYSQ
	GSKGPGEDFRMATLYSRTQTPRAELKEKFTAFCKAQGFTEDTIVFLPQTDKCMTEQ
	SEQ ID NO: 137	487 bp
NOV32b,	CCGGACACCCGCTCTGCTGCAGGAGAATGGCTACTCATCACACGCTGTGGATGGGACTGGCCCTGCT
CG57760-02
DNA Sequence	GGGGGTGCTGGGCGACCTGCAGGCAGCACCGGAGGCCCAGGTCTCCGTGCAGCCCAACTTACAGCAG
	CGCGTACTGGTGGAGACCGACTACGACCAGTACGCGCTGCTGTACAGCCAGGGCAGCAAGGGCCCTG
	GCGAGGACTTCCGCATGGCCACCCTCTACAGCCGAACCCAGACCCCCAGGGCTGAGTTAAAGGAGAA
	ATTCACCGCCTTCTGCAAGGCCCAGGGCTTCACAGAGGATACCATTGTCTTCCTGCCCCAAACCGAT
	AAGTGCATGACGGAACAATAGGACTCCCCAGGGCTGAAGCTCGGATCCCGGCCAGCCAGGTGACCCC
	CACGCTCTGGATGTCTCTGCTCCAACTCGAGCTGGCTCCGGGAGAAGAAGGCGGCGTTGTCCATGTG
	CAAGTCTGTGGTGGCCCC
	ORF Start: ATG at 27	ORF Stop: TAG at 354
	SEQ ID NO: 138	109 aa	MW at 12216.8kD
NOV32b,	MATHHTLWMGLALLGVLGDLQAAPEAQVSVQPNLQQRVLVETDYDQYALLYSQGSKGPGEDFRMATL
CG57760-02
Protein Sequence	YSRTQTPRAELKEKFTAFCKAQGFTEDTIVFLPQTDKCMTEQ

[0521] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 32B.

TABLE 32B
Comparison of NOV32a against NOV32b.
		NOV32a	Identities/
		Residues/	Similarities for
	Protein	Match	the Matched
	Sequence	Residues	Region
	NOV32b	120 . . . 190	70/71 (98%)
		39 . . . 109	71/71 (99%)

[0522] Further analysis of the NOV32a protein yielded the following properties shown in Table 32C.

TABLE 32C
Protein Sequence Properties NOV32a
PSort     0.3700 probability located in outside; 0.1900
analysis: probability located in lysosome (lumen); 0.1507
          probability located in microbody (peroxisome);
          0.1000 probability located in endoplasmic
          reticulum (membrane)
SignalP   Cleavage site between residues 23 and 24
analysis:

[0523] 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 32D.

TABLE 32D
Geneseq Results for NOV32a
		NOV32a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAU31028	Novel human secreted	5 . . . 190	156/191 (81%)	7e−81
	protein #1519 - Homo	32 . . . 222	159/191 (82%)
	sapiens, 222 aa.
	[WO200179449-A2,
	25 OCT. 2001]
ABB57144	Mouse ischaemic condition	1 . . . 189	137/189 (72%)	2e−76
	related protein sequence SEQ	1 . . . 189	158/189 (83%)
	ID NO: 348 - Mus musculus,
	189 aa. [WO200188188-A2,
	22 NOV. 2001]
AAY71471	Human prostaglandin D2	1 . . . 137	137/137 (100%)	6e−76
	synthase (PD2 synthase) -	1 . . . 137	137/137 (100%)
	Homo sapiens, 137 aa.
	[WO200029576-A1,
	25 MAY 2000]
ABG60136	Human DITHP polypeptide	1 . . . 188	131/188 (69%)	8e−74
	#194 - Homo sapiens, 212	19 . . . 206	152/188 (80%)
	aa. [WO200220754-A2,
	14 MAR. 2002]
AAB90661	Xenopus cpl-1 protein, SEQ	26 . . . 189	70/164 (42%)	3e−39
	ID NO: 204 - Xenopus sp,	21 . . . 183	113/164 (68%)
	184 aa. [WO200121658-A1,
	29 MAR. 2001]

[0524] 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 32E.

TABLE 32E
Public BLASTP Results for NOV32a
		NOV32a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
P41222	Prostaglandin-H2 D-isomerase	1 . . . 190	190/190 (100%)	e−108
	precursor (EC 5.3.99.2)	1 . . . 190	190/190 (100%)
	(Prostaglandin-D synthase)
	(Glutathione-independent PGD
	synthetase) (Prostaglandin D2
	synthase) (PGD2 synthase)
	(PGDS2) (PGDS) (Beta-trace
	protein) - Homo sapiens
	(Human), 190 aa.
Q8WNM0	Prostaglandin D2 synthase -	1 . . . 190	188/190 (98%)	e−107
	Pongo pygmaeus (Orangutan),	1 . . . 190	188/190 (98%)
	190 aa.
Q8WNM1	Prostaglandin D2 synthase -	1 . . . 190	187/190 (98%)	e−106
	Gorilla gorilla (gorilla), 190 aa.	1 . . . 190	188/190 (98%)
Q9TUI1	Prostaglandin D synthase -	1 . . . 190	179/190 (94%)	e−102
	Macaca fuscata (Japanese	1 . . . 190	183/190 (96%)
	macaque), 190 aa.
Q29562	Prostaglandin-H2 D-isomerase	1 . . . 189	146/189 (77%)	7e−83
	precursor (EC 5.3.99.2)	1 . . . 189	160/189 (84%)
	(Prostaglandin-D synthase)
	(Glutathione-independent PGD
	synthetase) (Prostaglandin D2
	synthase) (PGD2 synthase)
	(PGDS2) - Ursus arctos (Brown
	bear) (Grizzly bear), 191 aa.

[0525] PFam analysis predicts that the NOV32a protein contains the domains shown in the Table 32F.

TABLE 32F
Domain Analysis of NOV32a
			Identities/
		NOV32a	Similarities for
	Pfam	Match	the Matched	Expect
	Domain	Region	Region	Value
	lipocalin	38 . . . 186	49/157 (31%)	4.9e−42
			125/157 (80%)

Example 33

[0526] 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: 139	4620 bp
NOV33a,	TTTGGGAGATGTCTAAGTGATTTTTTTTTTTTTCCCGGAAGGCAAATGGCTGGCGTGGAAGCACAAC
CG59361-01
DNA Sequence	CCGCTTTCACTCTTCGAATTTGTGCTTAGCTCTTTTCTTGTACCTTGCCACTCGTGACCAACATGCT
	GTGATGCGACTCGTGACCIACATGCTGTGATGTGTGCCGAGGGAGGAATTGGTCAGCTACACAACCT
	GGATCTTACCACAGTTTGGATATGACTGAGGCTCTCCAATGGGCCAGATATCACTGGCGACGGCTGA
	TCAGAGGTGCAACCAGGGATGATGATTCAGGGCCATACAACTATTCCTCGTTGCTCGCCTGTGGGCG
	CAAGTCCTCTCAGATCCCTAAACTGTCAGGAAGGCACCGGATTGTTGTTCCCCACATCCAGCCCTTC
	AAGGATGAGTATGAGAAGTTCTCCGGAGCCTATGTGAACAATCGAATACGAACAACAAAGTACACAC
	TTCTGAATTTTGTGCCAAGAAATTTATTTGAACAATTTCACACAGCTCCCAATTTATATTTCCTGTT
	CCTAGTTGTCCTGAACTGGGTACCTTTGGTAGAAGCCTTCCAAAAGGAAATCACCATGTTGCCTCTG
	GTGGTGGTCCTTACAATTATCGCAATTAAAGATGGCCTGGAAGATTATCCGAAATACAAAATTGACA
	AACAGATCAATAATTTAATAACTAAAGTTTATAGTAGGAAAGAGAAAAAATACATTGACCGACGCTG
	GAAAGACGTTACTOTTGCGGACTTTATTCGCCTCTCCTGCAACCAGGTCATCCCTGCAGACATGGTA
	CTACTCTTTTCCACTGATCCAGATGGAATCTGTCACATTGAGACTTCTGGTCTTGATGGAGAGAGCA
	ATTTAAAACAGAGGCAGGTGGTTCGGGGATATGCAGAACAGGACTCTGAAGTTGATCCTGAGAAGTT
	TTCCAGTAGGATAGAATGTGAAAGCCCAAACAATGACCTCAGCAGATTCCGAGGCTTCCTAGAACAT
	TCCAACAAAGAACGCGTGGGTCTCAGTAAAGAAAATTTGTTGCTTAGAGGATGCACCATTAGAAACA
	CAGAGGCTGTTGTGGGCATTGTGGTTTATGCAGGCCATGAAACCAAAGCAATGCTGAACAACAGTGG
	GCCACGGTATAAGCGCAGCAAATTAGAAAGAAGAGCAAACACAGATGTCCTCTGGTGTGTCATGCTT
	CTGGTCATAATGTGCTTAACTGGCGCAGTACGTCATGGAATCTGGCTGAGCAGGTATGAAAAGATGC
	ATTTTTTCAATGTTCCCGAGCCTGATGGACATATCATATCACCACTGTTGGCACGATTTTATATGTT
	TTGGACCATGATCATTTTGTTACAGGTCTTGATTCCTATTTCTCTCTATGTTTCCATCGAAATTGTG
	AAGCTTGGACAAATATATTTCATTCAAAGTGATGTGGATTTCTACAATGAAAAAATGGATTCTATTG
	TTCAGTGCCGAGCCCTGAACATCGCCGAGGATCTGGGACAGATTCAGTACCTCTTTTCCGATAAGAC
	AGGAACCCTCACTGAGAATAAGATGGTTTTTCGAAGATGTAGTGTGGCAGGATTTGATTACTGCCAT
	GAAGAAAATGCCAGGAGGTTGGAGTCCTATCAGGAAGCTGTCTCTGAAGATGAAGATTTTATAGACA
	CAGTCAGTGGTTCCCTCAGCAATATGGCAAAACCGAGAGCCCCCAGCTGCAGGACAGTTCATAATGG
	GCCTTTGGGAAATAAGCCCTCAAATCATCTTGCTGGGAGCTCTTTTACTCTACGAAGTGGAGAAGGA
	GCCAGTGAAGTGCCTCATTCCAGACAGGCTGCTTTCAGTAGCCCCATTGAAACAGACGTGGTACCAG
	ACACCAGGCTTTTAGACAAATTTAGTCAGATTACACCTCGGCTCTTTATGCCACTAGATGAGACCAT
	CCAAAATCCACCAATGGAAACTTTGTACATTATCGACTTTTTCATTGCATTGGCAATTTGCAACACA
	GTAGTGGTTTCTGCTCCTAACCAACCCCGACAAAAGATCAGACACCCTTCACTGGGGGGGTTGCCCA
	TTAAGTCTTTGGAAGAGATTAAAAGTCTTTTCCAGAGATGGTCTGTCCGAAGATCAAGTTCTCCATC
	GCTTAACAGTGGGAAAGAGCCATCTTCTGGAGTTCCAAACGCCTTTGTGAGCAGACTCCCTCTCTTT
	AGTCGAATGAAACCAGCTTCACCTGTGGAGGAAGAGGTCTCCCAGGTGTGTGAGAGCCCCCAGTGCT
	CCAGTAGCTCAGCTTGCTGCACAGAGACAGAGAAACAACACGGTGATGCAGGCCTCCTGAATGGCAA
	GGCAGAGTCCCTCCCTGGACAGCCATTGGCCTGCAACCTGTGTTATGAGGCCGAGAGCCCAGACGAA
	GCGGCCTTAGTGTATGCCGCCAGCGCTTACCAATGCACTTTACGGTCTCGGACACCAGAGCAGGTCA
	TGGTCGACTTTNCTGCTTTGGGACCATTAACATTTCAACTCCTACACATCCTGCCCTTTGACTCAGT
	AAGAAAAAGAATGTCTGTTGTGGTCCGACACCCTCTTTCCAATCAAGTTGTGGTGTATACGAAAGGC
	GCTGATTCTGTCATCATGGAGTTACTGTCGGTGGCTTCCCCACATGGAGCAAGTCTGGAGAAACAAC
	AGATGATAGTAAGGGAGAAAACCCAGAAGCACTTGGATGACTATGCCAAACAAGGCCTTCGTACTTT
	ATGTATAGCAAAGAAGGTCATGAGTGACACTGAATATGCAGAGTGGCTCAGGAATCATTTTTTAGCT
	GAAACCAGCATTGACAACAGGGAAGAATTACTACTTGAATCTGCCATGAGGTTGGAGAACAAACTTA
	CATTACTTGGTGCTACTGGCATTGAAGACCGTCTGCAGGAGGGAGTCCCTGAATCTATAGAAGCTCT
	TCACAAAGCGGGCATCAAGATCTGGATGCTGACAGGGGACAAGCAGGAGACAGCTGTCAACATACCT
	TATGCATGCAAACTACTGGAGCCAGATGACAACCTTTTTATCCTCAATACCCAAAGTAAAGATGCCT
	GTGGGATGCTGATGAGCACAATTTTGAAAGAACTTCAGAAGAAAACTCAAGCCCTGCCAGAGCAAGT
	GTCATTAAGTGAAGATTTACTTCAGCCTCCTGTCCCCCGGGACTCAGGGTTACGAGCTGGACTCATT
	ATCACTGGGAAGACCCTGGAGTTTGCCCTGCAAGAAAGTCTGCAAAAGCAGTTCCTGGAACTGACAT
	CTTGGTGTCAAGCTGTGGTCTGCTGCCGAGCCACACCGCTGCAGAAAAGTGAAGTGGTGAAATTGGT
	CCGCAGCCATCTCCAGGTGATGACCCTTGCTATTGGTGATGGTGCCAATGATGTTAGCATGATACAA
	GTGGCAGACATTGGGATAGGGGTCTCAGGTCAAGAAGGCATGCAGGCTGTGATGGCCAGTGACTTTG
	CCGTTTCTCAGTTCAAACATCTCAGCAAGCTCCTTCTTGTCCATGGACACTGGTGTTATACACGGCT
	TTCCAACATGATTCTCTATTTTTTCTATAAGAATGTGGCCTATGTGAACCTCCTTTTCTGGTACCAG
	TTCTTTTGTGGATTTTCAGGAACATCCATGACTGATTACTGGGTTTTGATCTTCTTCAACCTCCTCT
	TCACATCTGCCCCTCCTGTCATTTATGGTGTTTTGGAGAAAGATGPGTCTGCAGAGACCCTCATGCA
	ACTGCCTGAACTTTACAGAAGTGGTCAGAAATCAGAGGCATACTTACCCCATACCTTCTGGATCACC
	TTATTGGATGCTTTTTATCAAAGCCTGGTCTGCTTCTTTGTGCCTTATTTTACCTACCAGGGCTCAG
	ATACTGACATCTTTGCATTTGGAAACCCCCTGAACACAGCCGCTCTGTTCATCGTTCTCCTCCATCT
	GGTCATTGAAAGCAAGAGTTTGACTTGGATTCACTTGCTGGTCATCATTGGTAGCATCTTGTCTTAT
	TTTTTATTTGCCATAGTTTTTGGAGCCATGTGTGTAACTTGCAACCCACCATCCAACCCTTACTGGA
	TTATGCAGGAGCACATGCTGGATCCAGTATTCTACTTAGTTTGTATCCTCACGACGTCCATTGCTCT
	TCTGCCCAGGTTTGTATACAGAGTTCTTCAGGGATCCCTGTTTCCATCTCCAATTCTGAGAGCTAAG
	CACTTTGACAGACTAACTCCAGAGGAGAGGACTAAAGCTCTCAAGAAGTGGAGAGGGGCTGGAAAGA
	TGAATCAAGTGACATCAAAGTATGCTAACCAATCAGCTGGCAAGTCAGGAAGAAGACCCATGCCTGG
	CCCTTCTGCTGTATTTGCAATGAAGTCAGCAAGTTCCTGTGCTATTGAGCAAGGAAACTTATCTCTG
	TGTGAAACTGCTTTACATCAAGGCTACTCTGAAACTAAGGCCTTTGAGATGGCTGGACCCTCCAAAG
	GTAAAGAAAGCTAGATACCCTCCTTGGAGTTGCAAGTATTCTTTCAAGGTTGGAAGAGGGATTTTGA
	AGAGGTATCTCTCCAAGCAAGAATGACTTGTTTTTCCATAAGGGACATGAGCATTTTACTAGGC
	ORF Start: ATG at 223		ORF Stop: TAG at 4501
	SEQ ID NO: 140	1426 aa	MW at 160265.91W
NOV33a,	MTEALQWARYHWRRLIRGATRDDDSGPYNYSSLLACGRKSSQIPKLSGRHRIVVPHIQPFKDEYEKF
CG59361-01
Protein Sequence	SGAYVNNRIRTTKYTLLNFVPRNLFEQFHRAANLYFLFLVVLNWVPLVEAFQKEITMLPLVVVLTII
	AIKDGLEDYRKYKIDKQINNLITKVYSRKEKKYIDRRWKDVTVGDFIRLSCNEVIPADMVLLFSTDP
	DGICHIETSGLDGESNLKQRQVVRGYAEQDSEVDPEKFSSRIECESPNNDLSRFRGFLEHSNKERVG
	LSKENLLLRGCTIRNTEAVVGIVVYAGHETKAMLNNSGPRYKRSKLERRANTDVLWCVMLLVIMCLT
	GAVGHGIWLSRYEKMHFFNVPEPDGHIISFLLAGFYMFWTMIILLQVLIPISLYVSIEIVKLGQIYF
	IQSDVDFYNEKMDSIVQCRALNIAEDLGQIQYLFSDKTGTLTENKMVFRRCSVAGFDYCHEENARRL
	ESYQEAVSEDEDFIDTVSGSLSNMAKPRAPSCRTVHNGPLGNKPSNHLAGSSFTLGSGEGASEVPHS
	RQAAFSSPIETDVVPDTRLLDKFSQITPRLFMPLDETIQNPPMETLYIIDFFIALAICNTVVVSAPN
	QPRQKIRHPSLGGLPIKSLEEIKSLFQRWSVRRSSSPSLNSGKEPSSGVPNAFVSRLPLFSRMKPAS
	PVEEEVSQVCESPQCSSSSACCTETEKQHGDAGLLNGKAESLPGQPLACNLCYEAESPDEAALVYAA
	RAYQCTLRSRTPEQVMVDFXALGPLTFQLLHILPFDSVRKRMSVVVRHPLSNQVVVYTKGADSVIME
	LLSVASPDGASLEKQQMIVREKTQKHLDDYAKQGLRTLCIAKKVMSDTEYAEWLRNHFLAETSIDNR
	EELLLESAMRLENKLTLLGATGIEDRLQEGVPESIEALHKAGIKIWMLTGDKQETAVNIAYACKLLE
	PDDKLFILNTQSKDACGMLMSTILKELQKKTQALPEQVSLSEDLLQPPVPRDSGLRAGLIITGKTLE
	FALQESLQKQFLELTSWCQAVVCCRATPLQKSEVVKLVRSHLQVMTLAIGDGANDVSMIQVADIGIG
	VSGQEGMQAVMASDFAVSQFKHLSKLLLVHGHWCYTRLSNNILYFFYKNVAYVNLLFWYQFFCGFSG
	TSMTDYWVLIFFNLLFTSAPPVIYGVLEKDVSAETLMQLPELYRSGQKSEAYLPHTFWITLLDAFYQ
	SLVCFFVPYFTYQCSDTDIFAFGNPLNTAALFIVLLHLVIESKSLTWIHLLVIIGSILSYFLFAIVF
	GAMCVTCNPPSNPYWIMQEHMLDPVFYLVCILTTSIALLPRFVYRVLQGSLFPSPILRAKHFDRLTP
	EERTKALKKWRGAGKMNQVTSKYANQSAGKSGRRPMPGPSAVFAMKSASSCAIEQGNLSLCETALDQ
	GYSETKAFEMAGPSKGKES

[0527]

TABLE 33B
Protein Sequence Properties NOV33a
PSort     0.6471 probability located in mitochondrial inner membrane;
analysis: 0.6000 probability located in plasma membrane; 0.4000
          probability located in Golgi body; 0.3377 probability
          located in mitochondrial matrix space
SignalP   No Known Signal Sequence Predicted
analysis:

[0528] 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	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAE01984	Human ATPase-related	1 . . . 1426	1422/1426 (99%)	0.0
	protein #7 - Homo sapiens,	1 . . . 1426	1423/1426 (99%)
	1426 aa.
	[WO200134778-A2,
	17 MAY 2001]
AAE01982	Human ATPase-related	1 . . . 1252	1249/1252 (99%)	0.0
	protein #5 - Homo sapiens,	1 . . . 1252	1249/1252 (99%)
	1270 aa.
	[WO200134778-A2,
	17 MAY 2001]
AAE01980	Human ATPase-related	1 . . . 1056	1053/1056 (99%)	0.0
	protein #3 - Homo sapiens,	1 . . . 1056	1054/1056 (99%)
	1056 aa.
	[WO200134778-A2,
	17 MAY 2001]
AAE01978	Human ATPase-related	1 . . . 951	949/951 (99%)	0.0
	protein #1 - Homo sapiens,	1 . . . 951	949/951 (99%)
	972 aa. [WO200134778-A2,
	17 MAY 2001]
AAB95253	Human protein sequence	753 . . . 1426	673/674 (99%)	0.0
	SEQ ID NO: 17421 - Homo	1 . . . 674	673/674 (99%)
	sapiens, 674 aa.
	[EP1074617-A2,
	07 FEB. 2001]

[0529] 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
Q96SR3	CDNA FLJ14692 fis, clone	753 . . . 1426	673/674 (99%)	0.0
	NT2RP2005344, weakly	1 . . . 674	673/674 (99%)
	similar to probable
	calcium-transporting ATPase
	5 (EC 3.6.1.38) - Homo
	sapiens (Human), 674 aa.
O54827	Potential	73 . . . 1329	692/1274 (54%)	0.0
	phospholipid-transporting	65 . . . 1318	907/1274 (70%)
	ATPase VA (EC 3.6.3.1) -
	Mus musculus (Mouse),
	1508 aa.
O60312	Potential	73 . . . 1377	706/1315 (53%)	0.0
	phospholipid-transporting	61 . . . 1349	922/1315 (69%)
	ATPase VC (EC 3.6.3.1)
	(ATPVC)
	(Aminophospholipid
	translocase VC) - Homo
	sapiens (Human), 1499 aa.
Q9P241	Potential	777 . . . 1426	649/650 (99%)	0.0
	phospholipid-transporting	1 . . . 650	650/650 (99%)
	ATPase VD (EC 3.6.3.1)
	(ATPVD) - Homo sapiens
	(Human), 650 aa (fragment).
AAM20894	P locus fat-associated	163 . . . 1329	649/1194 (54%)	0.0
	ATPase - Mus musculus	1 . . . 1164	842/1194 (70%)
	(Mouse), 1354 aa
	(fragment).

[0530] PFam analysis predicts that the NOV33a protein contains the domains shown in the Table 33E.

TABLE 33E
Domain Analysis of NOV33a
			Identities/
			Similarities for
	Pfam	NOV33a Match	the Matched	Expect
	Domain	Region	Region	Value
	Hydrolase	432 . . . 1077	38/653 (6%)	0.17
			377/653 (58%)

Example 34

[0531] 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: 141	3198bp
NOV34a,	TTTGGGGCTGAAGTTCCCTGTGGGAGGCTGTTTTCTGAGGCAGCTGAGTGTTTACAGCCACTCAGCC
CG59444-01
DNA Sequence	CTGCTCTGCTCAGCTGAAGCAGAAAACAGAGACCTTTTGCATTACTTTGGTTCAAGAGCAAGACAGG
	ACGCGACTGCATGAGACCATGGCTGAGACACCTACTCCTCCAGGCACTGAGGAACTCCAGGGCATTC
	TGTGGGTCTCATCGGAAGCCAGCACCTCTACCTGTTCCTCAGAAGATCGTGGCCACCTGGGAAGCCA
	TCAGCCTGGGAAGGCAGCTGGTGCCTGAGTACTTCAACTTCGCCCATGATGTGTTGGATGTGTGGAG
	CGGCTGGAAGAGGCTGGACACCCCCCCCCAAATCCTGCCTTCTGGTGGGTCAATGGCACAGGAGCA
	GAGATCJAGTGGACATTTGAGGAGCTGGGGAAGCAGTCCAGGAAGGCAGCCAATGTGCTGGGGGGTG
	CATGCGGCCTCCAGCCTCGGGACAGAATGATGCTGGTACTCCCACGGCTCCCGGAGTGGTGGCTGGT
	CAGTGTGGCTTGCATGCGGACAGGGACTGTGATGATTCCGGGTGTGACTCAGCTGACAGAGAAGGAC
	CTCAAGTACCGGCTGCACGCGTCCAGGGCCAAGTCCATTATCACCAGTGACTCCCTAGCTCCAAGGG
	TGGATGCCATCAGTGCCGAATGCCCCTCCCTCCAGACCAAGCTGCTGGTGTCAGACAGCAGTCGGCC
	AGGCTGGTTGAACTTCAGGGAACTCCTCCGGGAGGCTTCTACAGAGCACAACTGCATGAGGACAAAG
	AGTCGAGACCCGCTGGCCATCTACTTTACCAAGCGGGAACCACCGGGGGCCCCCAAGATGGTCGAGC
	ACTCCCAGAGCAGCTACGGACTGGGTTTTGTGGCCAGCGGAAGACGGTGGGTGGCCTTGACCGAATC
	TGACATCTTCTGGAACACGACTGACACTGGCTGGGTGAAGGCAGCCTGGACTCTCTTCTCTGCCTGG
	CCTAATGGATCTTGCATTTTTGTGCATGAGCTGCCCCGAGTTGATGCCAAAGTTATCCTGAATACTC
	TCTCCAAATTCCCGATAACCACCCTCTGCTGTGTCCCAACCATCTTTCGGCTGCTTGTGCAGGAGGA
	TCTGACCAGGTACCAGTTTCAGAGCTTCAGGCACTGTCTGACCGGAGGAGAGGCCCTCAACCCTGAC
	GTGAGGGAGAAGTGGAAACACCAGACTGGTGTGGAGCTGTACGAAGGCTATGGCCAGTCTGAAACGG
	TTGTCATCTGTGCCAATCCAAAAGGCATGAAAATCAAGTCTGGATCCATGGGGAAGGCGTCCCCACC
	CTACGATGTGCAGATTGTGGATGATGAGGGCAACGTCCTGCCTCCTGGAGAAGAGGGGAATGTTGCC
	GTCCGTATCAGACCCACTCGGCCCTTCTGTTTCTTCAATTGCTATTTGGACAATCCTGAGAAGACAG
	CTGCATCAGAACAAGGGGACTTTTACATCACAGGGGACCGAGCTCGCATGGACAAGGATGGCTACTT
	TTGGTTCATGCGAAGAAACGACGATGTGATCAATTCTTCAAGCTACCGGATCGGGCCTGTTGAAGTG
	GAAAGTGCCCTGGCAGAGCATCCTGCTGTCCTGGAGTCGGCTGTGGTCAGCAGCCCAGACCCCATCA
	GGGGAGAGGTGGTAAAGGCATTTATAGTCCTTACTCCAGCCTACTCCTCTCATGACCCAGAGGCACT
	AACGCGGGAACTCCAGGAGCATGTGAAAAGGGTGACTGCTCCATACAAATACCCCAGGAAGGTGGCC
	TTTGTTTCAGAACTTGCCAAAGACGGTTTCTGGAAAGATCCAAAGGAGTAAATTGCCAAGTCAGGAG
	TGGGGGAAATGAGGTGCACCCCAGGAAGGCCCCGTAGACCTCCGAAGACTCCACAAGAAACTAATGG
	ATCACTGGTCAGTCCCCATGGGGAGCATCATCTCTTCGACCCTAAAGATGTCAAAGGTGTGCAGCTT
	CCAAACGGCATCCCCAGGATCACTGGGCAATGCTGGAAAGAGCAAAAGAATATCATTGGCCCTGATC
	ACATAGATGCTGCGCCGCCTAGCAAATGCTTGGTGGTTCGACATCTCCCTCTGTCTGGGGGCAGGCT
	CAGCATCTGCCCACTGGTCTCACTAAGAGCTTTCAGATTTCCCTCCATAGGACAGGTTACCATAGAC
	TTCGGGCACTTGTGGGTACTCATTCTCTGCCAGTGGGAATGTAAAGGCTTCATCCTTTGTATGTAAC
	CATPTGGCAAAAGTATGCAGGAACATAAAATAAAATATCCTTTAGCTCAGAAATTCTATCTTCGGGA
	GTCACCACAAAAGAAAAAAATCAAAATGCAGAAAATGTGTGATGCACTAAGATGATCACACAGCATT
	AAAACTAAAAAAAAAAAAGAAAAAATTAACAATTAACATCCAAACAACAAGGAAATGATTAACAAAA
	TTGTAGTAGATTAACTCAATTACATATGATGTAGCCACTAAAATATTTGAGAGCAGTTTAGTATGTC
	TTGGGAAAAGTGTAAGCTATATTAATTTTAAAAATCAGAGCAAAAATATTCATACTGGAGAATCCCA
	ACTCTGAAAAATAAAGGGAAAACTCTGGTTAATTGTAATCCTCCTGGAGATTGAGGAGGGAGGGAGA
	GAAAATAATGGATGGPAGTTTTTCTTCTTCCTTTTTCCATTACATTTCTGTATTTTCCAAGTTTTTG
	TACGAAGCACATATAACTATTTTAATGAAAAAGTTATGTTAAAGAAAGCATACTCTGCTTCATGTCT
	AGTTCTTCCTCCACATACTCATACATCAACCCCAAAGACTGCTGTATTATGTCTGTATTAGTCAGCA
	TTCTCCAGAGAAGGAGAAGCAATAGGACATATATAGACATAGGAGAGGGGATTTATGATGGGAATTG
	GCTCACTCGATTTTGGA~GCTGAGAAGTTCCACAATCTACCATCTGCATGCTGGAGATCCAGGAAAC
	CCCGTGGTATAATTCCATCTGAGTCCAAAGGCCTGGTATTTGTCATATGCCTCGGCTCCTCAAACTG
	CAGCAAACAAACTCTATGGAAGAGAAAAAAATGGGACTCCAGAGACTTGAAATCACAGCCACTTGTC
	AGATGCAGCCCCCAACTCAGCTGCACGAGCTTAGCCAAATTTCTAGTCC
	ORF Start: ATG at 145		ORF Stop: TAA at 1858
	SEQ ID NO: 142	571 aa	MW at 64041.6kD
NOV34a,	MRPWLRHLVLQALRNSRAFCGSHGKPAPLPVPQKIVATWEAISLGRQLVPEYFNFAHDVLDVWSRLE
C059444-01
Protein Sequence	EAGHRPPNPAFWWVNGTGAEIKWTFEELGKQSRKAANVLGGACGLQPGDRIHLVLPRLPEWWLVSVA
	CMRTGTVMIPGVTQLTEKDLKYRLQASRAKSIITSDSLAPRVDAISAECPSLQTKLLVSDSSRPGWL
	NFRELLREASTEHNCMRTKSRDPLAIYFTKREPPGAPKMVEHSQSSYGLGFVASCRRWVALTESDIF
	WNTTDTGWVKAAWTLFSAWPNGSCIFVHELPRVDAKVILNTLSKFPITTLCCVPTIFRLLVQEDLTR
	YQFQSLRHCLTGGEALNPDVREHWKNQTGVELYEGYGQSETVVICANPKGMKTKSGSMGKASPPYDV
	QIVDDEGNVLPPGEEGNVAVRIRPTRPFCFFNCYLDNPEKTAASEQGDFYITGDRARMDKDGYFWFM
	GRNDDVINSSSYRIGPVEVESALAEHPAVLESAVVSSPDPIRGEVVKAFIVLTPAYSSHDPEALTRE
	LQEHVKRVTAPYKYPRKVAFVSELAKDGFWKDPKE
	SEQ ID NO: 143	1875 bp
NOV34b,	AGCTGAAGCAGAAAACAGAGACCTTTTGCATTACTTTGGTTCAAGAGCAAGACAGGAGGCGACTGCA
CG59444-02
DNA Sequence	TGAGACCATGGCTGAGACACCTAGTCCTCCAGGCACTGAGGAACTCCAGGGCATTCTGTGGGTCTCA
	TGGGAAGCCAGCACCTCTACCTGTTCCTCAGAAGATCGTGGCCACCTGGGAAGCCATCAGCCTGGGA
	AGGCAGCTGGTGCCTGAGTACTTCAACTTCGCCCATGATGTGCTGGATGTGTGGAGTCAGCTCGAAG
	AGGCTGGACACCGCCCCCCAAATCCTGCCTTCTGGTGGGTCAATGGCACAGGAGCAGAGATCAAGTG
	GAGCTTTGAGGAGCTGGGGAAGCAGTCCAGGAAGGCAACCAATGTGCTGGGGGGTGCATGCGGCCTG
	CAGCCTGGGGACAGAATGATGCTGGTACTCCCACGGCTCCCGGAGTGGTGGCTGGTCAGTGTGGCTT
	CCATGCGGACAGGGACTGTGATGATTCCGGGTGTGACTCAGCTGACAGAGAAGGACCTCAAGTACCG
	GCTGCAGGCGTCCAGCGCCAAGTCCATTATCACCAGTGACTCCCTAGCTCCAAGGGTGGATGCCATC
	AGTGCCGAATGCCCCTCCCTCCAGACCAAACTGCTGGTGTCAGACAGCAGTCGGCCACCCTGGTTGA
	ACTTCAGGGAACTCCTCCGCGAGGCTTCTACAGAGCACAACTGCGTGAGGACAAAGAGTCGAGACCC
	GCTGGCCATCTACTTTACCAGCGGAACCACCGGGGCCCCCAAGATGGTCGAGCACTCCCAGAGCAGC
	TACGGTCTGGGTTTTGTGCCCAGCGGAAGACGGTGGGTGGCCTTGACCGAATCTGACATCTTCTAGA
	ACACGACTGACACTGGCTGGGTGAAGGCAGCCTGGACTCTCTTCTCTCCCTGGCCTAATGGATCTTG
	CATTTTTGTACATCAGCTGCCCCGAGTTGATGCCAAACTTATCCTGAATACTCTCTCCAAATTCCCG
	ATAACCACCCTCTGCTGTGTCCCAACCATCTTTCGGCTGCTTGTGCAGGAGGATCTGACCAAATACC
	AGTTTCAGAGCCTGAGGCACTGTCTGACCGGACGAGAGGCCCTCAACCCTGACGTGACCGAGAGATG
	GAAACACCAGACTGGTGTGGAGCTGTACGAACGCTATGGCCAGTCTGAACGCATTGTCATCTCTGCC
	AATCCAAAAGGCATGAAAATCAAGTCTGGATCCATGGGGAAGGCGTCCCCACCCTACGATGTGCAGA
	TTGTGGATGATGAGGGCAACGTCCTGCCTCCTGGAGAAGAGGGGAATGTTGCCGTCCGTATCACACC
	CACTCGGCCCTTCTGTTTCTTCAATTGCTATTTGGACAATCCTGAGAAGACAGCTGCATCAGAACAA
	GGGGACTTTTACATCACAGGGGACCGAGCTCGCATGGACAAGGATGGCTACTTTTGGTTCATCGGAA
	GAAACGACGATGTGATCAATTCTTCAAGCTACCGGATCGGGCCTGTTGAAGTGGAAAGTGCCCTGGC
	AGAGCATCCTGCTGTCCTGGAGTCGGCTGTGGTCAGCAGCCCAGACCCCATCAGGGGACACGTCGTA
	AAGGCATTTATAGTCCTTACTCCAGCCTACTCCTCTCATGACCCAGAGGCACTAACGCGGGAACTCC
	AGGAGCATGTGAAAAGGGTGACTGCTCCATACAAATACCCCAGGAAGGTGGCCTTTGTTTCAGAACT
	GCCAAAGACGGTTTCTGGAAAGATCCAAAGGAGTAAATTGCGAAGTCAGGAGTGGGGGAAATGAGAT
	AACACCCCAGGAAGGCCCCGTAGACCTCCGAAGACTCCACAAGAAACTAATGGATCACTGGTCAGTC
	ORF Start: ATG at 67		ORF Stop: TGA at 1804
	SEQ ID NO: 144	579 aa	MW at 64699.3kD
NOV34b,	MRPWLRHLVLQALRNSRAFCGSHGKPAPLPVPQKIVATWEAISLGRQLVPEYFNFAHDVLDVWSQLE
CG59444-02
Protein Sequence	EAGHRPPNPAFWWVNGTGAEIKWSFEELGKQSRKAANVLGGACGLQPGDRMMLVLPRLPEWWLVSVA
	CMRTGTVMIPGVTQLTEKDLKYRLQASRAKSIITSDSLAPRVDAISAECPSLQTKLLVSDSSRPGWL
	NFRELLREASTEHNCVRTKSRDPLAIYFTSGTTGAPKMVEHSQSSYGLGFVASGRRWVALTESDIFW
	NTTDTGWVKAAWTLFSAWPNGSCIFVHELPRVDAKVILNTLSKFPITTLCCVPTIFRLLVQEDLTRY
	QFQSLRHCLTGGEALNPDVREKWXHQTGVELYEGYGQSETVVICANPKGMKIKSGSMGKASPPYDVQ
	IVDDEGNVLPPGEEGNVAVRIRPTRPFCFFNCYLDNPEKTAASEQGDFYITGDRAPMDKDGYFWFMG
	RNDDVINSSSYRIGPVEVESALAEHPAVLESAVVSSPDPIRGEVVKAFIVLTPAYSSHDPEALTREL
	QEHVKRVTAPYKYPRKVAFVSELPKTVSGKIQRSKLRSQEWGK

[0532] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 34B.

TABLE 34B
Comparison of NOV34a against NOV34b.
		Identities/
		Similarities for
Protein	NOV34a Residues/	the Matched
Sequence	Match Residues	Region
NOV34b	1 . . . 562	541/562 (96%)
	1 . . . 561	544/562 (96%)

[0533] Further analysis of the NOV34a protein yielded the following properties shown in Table 34C.

TABLE 34C
Protein Sequence Properties NOV34a
PSort     0.7862 probability located in mitochondrial matrix space;
analysis: 0.5877 probability located in microbody (peroxisome);
          0.4642 probability located in mitochondrial inner membrane;
          0.4642 probability located in mitochondrial
          intermembrane space
SignalP   Cleavage site between residues 21 and 22
analysis:

[0534] 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 34D.

TABLE 34D
Geneseq Results for NOV34a
		NOV34a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAE22093	Human kidney specific renal	41 . . . 562	287/523 (54%)	e−174
	cell carcinoma (KSRCC)	32 . . . 552	378/523 (71%)
	protein - Homo sapiens, 577
	aa. [WO200216595-A2,
	28 FEB. 2002]
AAB43245	Human ORFX ORF3009	50 . . . 562	284/514 (55%)	e−173
	polypeptide sequence SEQ	1 . . . 512	373/514 (72%)
	ID NO: 6018 - Homo sapiens,
	537 aa. [WO200058473-A2,
	05 OCT. 2000]
AAU23054	Novel human enzyme	336 . . . 562	224/227 (98%)	e−130
	polypeptide #140 - Homo	2 . . . 228	224/227 (98%)
	sapiens, 246 aa.
	[WO200155301-A2,
	02 AUG. 2001]
ABB53263	Human polypeptide #3 -	47 . . . 562	235/521 (45%)	e−129
	Homo sapiens, 583 aa.	43 . . . 559	337/521 (64%)
	[WO200181363-A1,
	01 NOV. 2001]
ABB53262	Human polypeptide #2 -	47 . . . 483	198/439 (45%)	e−114
	Homo sapiens, 480 aa.	43 . . . 480	295/439 (67%)
	[WO200181363-A1,
	01 NOV. 2001]

[0535] 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 34E.

TABLE 34E
Public BLASTP Results for NOV34a
		NOV34a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9NWV3	CDNA FLJ20581 fis, clone	1 . . . 571	570/571 (99%)	0.0
	REC00491 - Homo sapiens	1 . . . 571	571/571 (99%)
	(Human), 571 aa.
O60363	SA gene - Homo sapiens	49 . . . 562	317/515 (61%)	0.0
	(Human), 578 aa.	46 . . . 559	407/515 (78%)
Q13732	SA SA gene product	49 . . . 562	317/515 (61%)	0.0
	precursor - Homo sapiens	46 . . . 559	407/515 (78%)
	(Human), 578 aa.
Q91WI1	SA rat	49 . . . 562	313/515 (60%)	0.0
	hypertension-associated	46 . . . 559	405/515 (77%)
	homolog (SA protein) - Mus
	musculus (Mouse), 578 aa.
Q9Z2F3	SA protein - Mus musculus	49 . . . 562	312/515 (60%)	0.0
	(Mouse), 578 aa.	46 . . . 559	404/515 (77%)

[0536] PFam analysis predicts that the NOV34a protein contains the domains shown in the Table 34F.

TABLE 34F
Domain Analysis of NOV34a
		Identities/
		Similarities for
Pfam	NOV34a Match	the Matched	Expect
Domain	Region	Region	Value
AMP-binding	91 . . . 230	28/140 (20%)	4.6e−17
		92/140 (66%)
AMP-binding	236 . . . 503	88/277 (32%)	1.4e−67
		209/277 (75%)

Example 35

[0537] 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: 145	846bp
NOV35a,	ACCACCATGAATCCACTCCTGATCCTTACCTTTGTGGCAGCTGCTCTTGCTGCCCCCTTTGATGATG
CG59482-01
DNA Sequence	ATGACAGATCGTTGGGGGCTACAACTGTGAGGAGAATTCTGTCCCCTACCACGTGTGCCCTGAATTC
	TGGCTACCACTTCTGTGGTGGCTCCCTCATCAACGAACAGTGGGTGGTATCAGCAGGCCACTGCTAC
	AGTCCCGCATCCAGGTGAGACTGGAGAGCACAACATCGAAGTCCTGGAGGGGAATATGAGCAGTTCA
	TCAATGCAGCCAGATCATCCGCCACCCCCAATACGACAGGAAGACTCTGAACAAATCACATCATCTT
	AATCAAGCTCTCCTCACGTGCAGTAATCAACGCCCGCGTGTCCACCATCTCTCTGCCCACCGCCCCT
	CCAGCCACTGGCACGAAGTGCCTCATCTCTGGCTGGGGCAACACTGCGAGCTCTGGCGCCGACTACC
	CAGACGAGCTGCAGTGCCTGGACGCTCCTGTGCTGAGCCAGGCTAAGTGTGAAGCCTCCTACCATGG
	AAAGATTACCAGCAACATGTTCTGTGTGGGCTTCCTTGAGGGAGGCAAGGATTCATGTCAGGGTGAT
	TCTGGTGGCCCTGTGGTCTGCAATGGACAGCTCCAAGGAGTTGTCTCCTGGGGTGATGGCTGTGCCC
	AGAAGAACAAGCCTGGAGTCTACACCAAGGTCTACAACTACGTGAAATGGATTAAGAACACCATAGC
	TGCCAACAGCTAAACCCCCCAGTATCTCTTCAGTCTCTATACCAATAAAGTGACGCTCGAGCCCTAT
	AGTGAGTCGTATTAGGATGTGCCTTCACGTCGTCAGCATCGT
	ORF Start: ATG at 7		ORF Stop: TAA at 748
	SEQ ID NO: 146	247 aa	MW at 26557.8kD
NOV35a,	MNPLLILTFVAAALAAPFDDDDKIVGCYNCEENSVPYQVSLNSGYHFCGGSLINEQWVVSAGHCYXS
CG59482-01
Protein Sequence	RIQVRLGEHNIEVLEGNEQFINAAKIIRHPQYDRKTLNNDIMLIKLSSRAVINARVSTISLPTAPPA
	TGTKCLISGWGNTASSGADYPDELQCLDAPVLSQAKCEASYPGKITSNMFCVGFLEGGKDSCQGDSG
	GPVVCNGQLQGVVSWGDGCAQKNKPGVYTKVYNYVKWIKNTIAANS
	SEQ ID NO: 147	506 bp
NOV35b,	CATGAATCCACTCCTGATCCTTACCTTTGTGGCAGCTGCTCTAATCAACGCCCGCGTGTCCACCATC
CG59482-02
DNA Sequence	TCTCTGCCCACCGCCCCTCCAGCCACTGGCACGAAGTGCCTCATCTCTGGCTGGGGCAACACTGCGA
	GCTCTGGCGCCGACTACCCAGACGAGCTGCAGTGCCTGGATGCTCCTGTGCTGAGCCAGCCTAAGTG
	TGAAGCCTCCTACCCTGGAAAGATTACCAGCAACATGTTCTGTGTGGGCTTCCTTGAGGGAGGCAAG
	GATTCATGTCAGGGTGATTCTGGTGGCCCTGTGGTCTGCAATGGACAGCTCCAACGAGTTGTCTCCT
	GGGGTGATGGCTGTGCCCAGAAGAACAAGCCTGGAGTCTACACCAAGGTCTACAACTATGTGAAATG
	GATTAAGAACACCATAGCTGCCAATAGCTAAAGCCCCCAGTATCTCTTCAGTCTCTATACCAATAAA
	GTGACCCTGTTCTCACAAAAAAAAAAAAAAAAAAACCC
	ORF Start: ATG at 2		ORF Stop: TAA at 431
	SEQ ID NO: 148	143 aa	MW at 14865.8kD
NOV35b,	MNPLLILTFVAAALINARVSTISLPTAPPATGTKCLISGWGNTASSGADYPDELQCLDAPVLSQAKC
CG59482-02
Protein Sequence	EASYPGKITSNMFCVGFLEGGKDSCQGDSGGPVVCNGQLQGVVSWGDGCAQKNRPCVYTKVYNYVKW
	IKNTIAANS
	SEQ ID NO 149	837 bp
NOV35c,	GCAAQTGTGAATCGCCCTTCATGAATCCACTCCTGATCCTTACCTTTGTGGCAGCTGCTCTTGCTCC
CG59482-03
DNA Sequence	CCCCTTTGATGATGATGACAAGATCGTTGGGGGCTACAACTGTGAGGAGAATTCTCTCCCCTACCAG
	GTGTCCCTGAATTCTGGCTACCACTTCTGTGGTGGCTCCCTCATCAACGAACAGTGGGTGGTATCAG
	CAGGCCACTGCTACAAGTCCCGCATCCAGGTGAGACTGGGAGAGCACAACATCGAAGTCCTGGAGCG
	GAATGAGCAGTTCATCATGCAGCCAAGATCATCCGCCACCCCCAATACGACAGGAAGGACTCTGAAC
	AATGACATCATGTTAATCAAGCTCTCCTCACGTGCAGTAATCAACGCCCGCGTGTCCACCATCTCTC
	TGCCCACCGCCCCTCCAGCCACTGGCACGAAGTGCCTCATCTCTGGCTGGGGCAACACTGCGAGCTC
	TGGCGCCGACTACCCAGACGAGCTGCAGTGCCTGGACGCTCCTGTGCTGAGCCAGGCTAAGTGTGAA
	GCCTCCTACCCTGGAAAGATTACCAGCAACATGTTCTGTGTGGGCTTCCTTGAGGGAGGCAAG~ATT
	CATCTCAGGGTGATTCTGGTGGCCCTGTGGTCTGCAATGGACAGCTCCAAGGAGTTGTCTCCTCGGG
	TGATGGCTGTGCCCAGAAGAACAAGCCTGGAGTCTACACCAAGGTCTACAACTATGTGAAATGGATT
	AAGAACACCATAGCTGCCAATAGCTAAAGCCCCCAGTATCTCTTCAGTCTCTATACCAATAAAGTGA
	CCCTGTTCCTCACAAAAAAAGGGCGATTCCAGA
	ORF Start: ATG at 21		ORF Stop: TAA at 762
	SEQ ID NO: 150	247 aa	MW at 26557.8kD
NOV35c,	MNPLLILTFVAAALAAPFDDDDKIVGGYNCEENSVPYQVSLNSGYHFCGGSLINEQWVVSAGHCYKS
CG59482-03
Protein Sequence	RIQVRLGEHNIEVLECNEQFINAAXIIRHPQYDRKTLNNDIMLIKLSSRAVINARVSTISLPTAPPA
	TGTKCLTSGWGNTASSGADYPDELQCLDAPVLSQAKCEASYPGKITSNMFCVGFLEGGKDSCQGDSG
	GPVVCNGQLQGVVSWGDGCAQKNKPGVYTKVYNYVKWIKNTTAANS

[0538] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 35B.

TABLE 35B
Comparison of NOV35a against NOV35b and NOV35c.
			Identities/
			Similarities for
	Protein	NOV35a Residues/	the Matched
	Sequence	Match Residues	Region
	NOV35b	106 . . . 247	131/142 (92%)
		2 . . . 143	137/142 (96%)
	NOV35c	1 . . . 247	235/247 (95%)
		1 . . . 247	235/247 (95%)

[0539] Further analysis of the NOV35a protein yielded the following properties shown in Table 35C.

TABLE 35C
Protein Sequence Properties NOV35a
PSort     0.5708 probability located in outside; 0.1000
analysis: probability located in endoplasmic reticulum
          (membrane); 0.1000 probability located in
          endoplasmic reticulum (lumen); 0.1000
          probability located in lysosome (lumen)
SignalP   Cleavage site between residues 16 and 17
analysis:

[0540] A search of the NOV35a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 35D.

TABLE 35D
Geneseq Results for NOV35a
			Identities/
			Similarities for
Geneseq	Protein/Organism/Length	NOV35a Residues/	the Matched	Expect
Identifier	[Patent #, Date]	Match Residues	Region	Value
AAB21321	Human trypsinogen - Homo	1 . . . 247	247/247 (100%)	e−147
	sapiens, 247 aa.	1 . . . 247	247/247 (100%)
	[WO200053776-A2,
	14 SEP. 2000]
AAB21316	Human trypsinogen - Homo	1 . . . 241	241/241 (100%)	e−143
	sapiens, 241 aa.	1 . . . 241	241/241 (100%)
	[WO200053776-A2,
	14 SEP. 2000]
AAW93488	Human TRYI trypsinogen	19 . . . 247	229/229 (100%)	e−137
	variant protein - Homo	2 . . . 230	229/229 (100%)
	sapiens, 230 aa.
	[WO9910503-A1,
	04 MAR. 1999]
AAB98503	Human trypsin serine	23 . . . 247	225/225 (100%)	e−134
	protease catalytic domain -	1 . . . 225	225/225 (100%)
	Homo sapiens, 225 aa.
	[WO200129056-A1,
	26 APR. 2001]
AAY31160	Human trypsin serine	24 . . . 247	224/224 (100%)	e−133
	protease protein domain -	1 . . . 224	224/224 (100%)
	Homo sapiens, 224 aa.
	[US5948892-A,
	07 SEP. 1999]

[0541] 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 35E.

TABLE 35E
Public BLASTP Results for NOV35a
			Identities/
Protein			Similarities for
Accession		NOV35a Residues/	the Matched	Expect
Number	Protein/Organism/Length	Match Residues	Portion	Value
P07477	Trypsin I precursor (EC	1 . . . 247	247/247 (100%)	e−146
	3.4.21.4) (Cationic	1 . . . 247	247/247 (100%)
	trypsinogen) - Homo sapiens
	(Human), 247 aa.
P07478	Trypsin II precursor (EC	1 . . . 247	221/247 (89%)	e−130
	3.4.21.4) (Anionic	1 . . . 247	236/247 (95%)
	trypsinogen) - Homo sapiens
	(Human), 247 aa.
AAC80208	TRYPSINOGEN C - Homo	1 . . . 247	219/247 (88%)	e−129
	sapiens (Human), 247 aa.	1 . . . 247	230/247 (92%)
AAC13322	MESOTRYPSINOGEN -	1 . . . 247	214/247 (86%)	e−127
	Homo sapiens (Human), 247	1 . . . 247	231/247 (92%)
	aa.
AAH30260	Protease, serine, 2 (trypsin 2) -	1 . . . 239	214/239 (89%)	e−126
	Homo sapiens (Human),	1 . . . 239	228/239 (94%)
	239 aa.

[0542] PFam analysis predicts that the NOV35a protein contains the domains shown in the Table 35F.

TABLE 35F
Domain Analysis of NOV35a
			Identities/
		NOV35a	Similarities for
	Pfam	Match	the Matched	Expect
	Domain	Region	Region	Value
	trypsin	24 . . . 239	113/262 (43%)	1.5e−111
			198/262 (76%)

Example 36

[0543] 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: 151	3080 bp
NOV36a,	TTCCAGCCGGCAGGATGGAGGACGAGGAAGGCCCTGAGTATGGCAAACCTGACTTTGTGCTTTTGGA
CG59522-01
DNA Sequence	CCAAGTGACCATGGACGACTTCATGAGGAACCTGCAGCTCAGGTTCGAGAAGGGCCGCATCTACACC
	TACATCGGTGAGGTGCTGGTGTCCGTGAACCCCTACCAGGAGCTGCCCCTGTATGGGCCTGAAGCCA
	TCGCCAGGTACCAGGGCCGTGAGCTCTATGAGCGGCCACCCCATCTCTATGCTGTGGCCGAACGCGC
	CTACAAGGCAATGAAGCACCGGTCCAGGGACACCTGCATCGTCATCTCAGGGGAGAGTGGGGCAGGG
	AAGACAGAAGCCAGTAAGCACATCATGCAGTACATCGCTGCTGTCACCAATCCTAGCCAGAGGGCTG
	AGGTGGAGAGGGTCAAGGACGTGCTGCTCAAGTCCACCTGTGTGCTGGAGGCCTTTGGCAATGCCCG
	CACCAACCGCAATCACAACTCCAGCCGCTTTGGCAAGTACATGGACATCAACTTTGACTTCAAGGGG
	GACCCGATCGGAGGACACATCCACAGCTACCTACTGGAGAAGTCTCGGGTCCTCAAGCAGCACGTGG
	GTGAAAGAAACTTCCACGCCTTCTACCAATTGCTGAGAGGCAGTGAGGACAAGCAGCTGCATGAACT
	GCACTTGGAGAGAAACCCTGCTGTATACAATTTCACACACCAGGGAGCAGGACTCAACATGACTGTC
	AGTGATGAGCAGAGCCACCAGGCAGTGACCGAGGCCATGAGGGTCATCGGCTTCAGTCCTGAAGAGG
	TGGAGTCTGTGCATCGCATCCTGGCTGCCATATTGCACCTGGGAAACATCGAGTTTGTGGAGACCGA
	GGAGGGTGGGCTGCAGAAGGAGGGCCTGGCAGTGGCCGAGGAGGCACTGGTGGACCATGTGGCTGAG
	CTGACGGCCACACCCCGGGACCTCGTGCTCCGCTCCCTGCTGGCTCGCACAGTTGCCTCGGGAGGCA
	GGGAACTCATAGAGAAGGGCCACACTGCACCTGAGGCCAGCTATGCCCGGGATGCCTGTGCCAAGGC
	AGTGTACCAGCGGCTGTTTGAGTGGGTGGTGAACAGGATCAACAGTGTCATGGAACCCCGGGGCCGG
	GATCCTCGGCGTGATGGCAAGGACACAGTCATTGGCGTGCTGGACATCTATGGCTTCGAGGTGTTTC
	CCGTCAACAGTTTCGAGCAGTTCTGCATCAACTACTGCAACGAGAAGCTCCAGCAGCTATTCATCCA
	GCTCATCCTGAAGCAGGAACAGGAAGAGTACGAGCGCGAGGGCATCACCTGGCAGAGCGTTGAGTAT
	TTCAACAACGCCACCATTGTGGATCTGGTGGAGCGGCCCCACCGTGGCATCCTGCCCGTGCTGGACG
	AGGCCTGCAGCTCTGCTGGCACCATCACTGACCGAATCTTCCTGCAGACCCTCGACATGCACCACCG
	CCATCACCTACACTACACCAGCCGCCAGCTCTGCCCCACAGACAAGACCATGGAGTTTGGCCGAGAC
	TTCCGGATCAAGCACTATGCAGCGGACGTCACGTACTCCGTGCAAGGCTTCATCGACAGAAACAGAG
	ATTTCCTCTTCCAGGACTTCAAGCGGCTGCTGTACAACAGCACGGACCCCACTCTACGGGCCATGTG
	GCCGGACGGGCAGCAGGACATCACAGAGGTCACCAAGCGCCCCCTGACGGCTGGCACACTCTTCAAG
	ACTCCATGGTGGCCCTGGTGGAGAACCTTGCCTCCAAGGAGCCCTTCTACGTCCGCTGCATCAAAGC
	CCAATGAGGACAAGGTAGCTGGGAAGCTGGATGAGAACCACTGTCGCCACCAGGTCGCATACCTAAG
	GCTGCTGCAGAATGTGAGGGTCCGCAGGGCTGGCTTCGCTTCCCGCCAGCCCTACTCTCGATTCCTG
	CTCAGGTACAAGATGACCTGTGAATACACATGGCCCAACCACCTGCTGGGCTCCGACAAGGCAGCCG
	TGAGCGCTCTCCTGCAGCAGCACGGGCTGCAGGGGGACGTCCACCTTTGGCCACAGCAGCTGTTCAT
	CCGCTCACCCCGGACACTGGTCACACTGGAGCAGAGCCGAGCCCGCCTCATCCCCATCATTGTGCTG
	CTATTGCAGAAGGCATGGCGGGGCACCTTGGCGAGGTGGCGCTGCCGGAGGCTGAGGGCTATCTACA
	CCATCATGCGCTGGTTCCGGAGACACAAGGTGCGGGCTCACCTAACTGAGCTGCAGCGGCGATTCCA
	GGCTGCAAGGCAGCCGCCACTCTACGGGCGTGACCTTGTGTGCCCGCTGCCCCCTGCTGTGCTGCAG
	CCCTTCCAGGACACCTGCCACGCACTCTTCTGCAGGTGGCGGCCCCCGCAGCTGGTGAAAGACATCC
	CCCCTTCAGACATGCCCCAGATCAAGGCCAAGGTGGCCGCCATCGGGGCCCTCCAAGGGCTTCGTCA
	GGACTGGGGCTGCCGACGGGCCTGGGCCCGAGACTACCTGTCCTCTGCCACTGACATTCCCACAGCA
	TCAAGCCTGTTTGCTCAGCGACTAAAGACACTTCAGGACAAAGATGGCTTCGGATCTGTGCTCTTTT
	CAAGCCATGTCCGCAAGGTGAACCGCTTCCACAAGATCCGGAACCGGGCCCTCCTGCTCACAGACCA
	GCACCTCTACAAGCTGGACCCTGACCGGCAGTACCGGGTCATGCGGGCCGTGCCCCTTGAGGCGGTG
	ACGGGGCTGAGCGTGACCAGCCGACGAGACCAGCTGGTGGTGCTGCACGCCCGCGCCCAGGACGACC
	TCGTGGTGTGCCTGCACCGCTCCCGGCCGCCATTGGACAACCGCGTTAAGGAGCTGGTGGGCGTGCT
	GGCCGCACACTGCCGCAGGGAGGGCCGCACCCTGGAGGTTCGCGTCTCCGACTGCATCCCACTAAGC
	CATCGCGGGGTCCGGCGCCTCATCTCCGTGGAGCCCAGGCCGGAGCAGCCAGAGCCCGATTTCCGCT
	GCGCTCGCGGCTCCTTCACCCTGCTCTGGCCCAGCCGCTGAGCGCCCCCACCCGCCGCACCCCGA
	ORF Start: ATG at 15		ORF Stop: TGA at 3054
	SEQ ID NO: 152	1013 aa	MW at 116O44.5kD
NOV36a,	MEDEEGPEYGKPDFVLLDQVTMEDFMRNLQLRFEKGRIYTYIGEVLVSVNPYQELPLYGPEAIARYQ
CG59522-01
Protein Sequence	GRELYERPPHLYAVANAAYXA(HRSRDTCIVISGESGAGKTEASKHIMQYIAAVTNPSPQRAEVERV
	KDVLLKSTCVLEAFGNARTNRNHNSSRFGKYMDINFDFKGDPIGGHIHSYLLEKSRVLKQHVGERNF
	HAFYQLLRGSEDKQLHELHLERNPAVYNFTHQGAGLNMTVSDEQSHQAVTEAMRVIGFSPEEVESVH
	RILAAILHLGNIEFVETEEGGLQKEGLAVAEEALVDHVAELTATPRDLVLRSLLARTVASGGRELIE
	KGHTAAEASYARDACAKAVYQRLFEWVVNRINSVMEPRGRDPRRDGKDTVIGVLDIYGFEVFPVNSF
	EQFCINYCNEKLQQLFIQLILKQEQEEYEREGITWQSVEYFNNATIVDLVERPHRGILAVLDEACSS
	AGTITDRIFLQTLDMHHRHHLHYTSRQLCPTDKTMEFGRDFRIKHYAGDVTYSVEGFIDFGEDFLFQ
	DFKRLLYNSTDPTLRAMWPDGQQDITEVTKRPLTAGTLFKNSMVALVENLASKEPFYVRCIKPNEDK
	VAGKLDENHCRHQVAYLGLLENVRVRRAGFASRQPYSRFLLRYKMTCEYTWPNHLLGSDKAAVSALL
	EQHGLQGDVAFGHSKLFIRSPRTLVTLEQSRARLIPIIVLLLQKAWRGTLARWRCRRLRAIYTIMRW
	FRRHKVRAHLAELQRRFQAARQPPLYGRDLVWPLPPAVLQPFQDTCHALFCRWRARQLVKNIPPSDM
	PQIKAKVAAMGALQGLRQDWGCRRAWARDYLSSATDNPTASSLFAQRLKTLQDKDGFGAVLFSSHIR
	KVNRFHKIRNRALLLTDQHLYXLDPDRQYRVAVPLEAVTGLSVTSCGDQLVVLIJARGQDDLKSJCL
	HRSRPPLDNRVGELVGVLAAHCRREGRTLEVRVSDCIPLSHRGVRRLISVEPRPEQPEPDFRCARGS
	FTLLWPSR
	SEQ ID NO: 153	3071 bp
NOV36b,	TTCCAGCCGGCAGGATGGAGGACGAGGAAGGCCCTGAGTATGGCGAACCTGACTTTGTGCTTTTGGA
CG59522-02
DNA Sequence	CCAGTGACCATGGAGGACTTCATGAGGAACCTGCAGCTCAGGTTCGAGAAAGGGCCGCATCTACACC
	TACATCGGTGAGGTGCTGGTGTCCGTGAACCCCTACCAGGAGCTGCCCCTGTATGGGCCTGAACACA
	TCGCCAGGTACCAGGGCCGTGAGCTCTATGAGCGGCCACCCCATCTCTATGCTGTGGCCAACGCCGC
	CTACAAGGCAATGAAGTACCGGTCCAGGGACACCTGCATCGTCATCTCAGGGGAGAGTAGAACAGGG
	AAGACAGAAGCCAGTAAGCACATCATGCAGTACATCGCTGCTGTCACCAATCCAAGCCAGAGGGCTG
	AGGTGGAGAGGTCAAGGACGTGCTGCTCAAGTCCACCTGTGTGCTGGAGGCCTTTGGCAAGTGCCCG
	CACCAACCGCAATCACAACTCCAGCCGCTTTGGCAAGTACATGGACATCAACTTTGACTTCAAGGGG
	GACCCGATCGGAGGACGCATCCACAGCTACCTACTGGAGAAGTCTCGGGTCCTCAAGCAGCACGTGG
	GTGAAAGAAACTTCCACGCCTTCTACCAATTGCTGAGAGGCAGTGAGGACAAGCAGCTGCATGAACT
	GCACTTGGAGAGAAACCCTGCTGTATACAATTTCACACACCAGGGAGCAGGACTCAACATGACTGTG
	CACAGTGCCTTGGACAGTGATGAGCAGAGCCACCAGGCAGTGACCGAGGCCATGAGGGTCATCAACT
	TCAGTCCTGAAGAGGTGGAGTCTGTGCATCGCATCCTGGCTGCCATATTGCACCTGGGAAACATCGA
	GTTTGTGGAGACGGAGGAGGGTGGGCTGCAGAAGGAGCGCCTGGCACTGGCCGAGCAGGCACTGGTG
	GACCATGTGGCTGAGCTGACGGCCACACCCCGGGACCTCGTGCTCCGCTCCCTGCTGGCTCGCACAG
	TTGCCTCCGGACGCAGGGAACTCATAGAGAAGGGCCACACTGCAGCTGAGGCCAGCTATGCCCGAAA
	TGCCTGTGCCAAGGCAGTGTACCAGCGGCTGTTTGAGTGGGTGGTGAACAGGATCAACAGTGTCATG
	GAACCCCGGGGCCGGGATCCTCGGCGTGATGGCAACGACACAGTCATTGGCGTGCTGGACATCTATG
	GCTTCGAGGTGTTTCCCGTCAACAGTTTCGAGCAGTTCTGCATCAACTACTGCAATGAGAAGCTGCA
	GCAGCTATTCATCCAGCTCATCCTGAAGCAGGAACAGGAAGAGTACGAGCGCGAGCGCATCACCTGG
	CAGAGCGTTGAGTATTTCAACAACGCCACCATTGTGGATCTGGTGGAGCGGCCCCACCGTGGCATCC
	TGGCCGTGCTGGACGAGGCCTGCAGCTCTGCTGGCACCATCACTGACCGAATCTTCCTGCAGACCCT
	GGACACGCACCACCGCCATCACCTACACTACACCAGCCGCCAGCTCTGCCCCACAGACAAGACCATG
	GAGTTTGGCCGAGACTTCCGGATCAAGCACTATGCAGGGCACGTCACGTACTCCGTGGAAGGCTTCA
	TCGACAAGAACAGAGATTTCCTCTTCCAGGACTTCAAGCGGCTGCTGTACAACAGCACGGACCCCAC
	TCTACGCGCCATGTGGCCGGACGGGCAGCAGGACATCACAGAGGTGACCAAGCGCCCCCTGACGGCT
	GGCACACTCTTCAAGAACTCCATGGTGGCCCTGGTGGAGAACCTTGCCTCCAAGGAGCCCTTCTACG
	TCCGCTGCATCAAGCCCAATGAGGACAAGGTAGCTGGGAAGCTGGATGAGAACCACTGTCGCCACCA
	GGTCGCATACCTGGGGCTGCTGGAGAATOTGAGGGTCCGCAGGGCTGGCTTCGCTTCCCGCCAGCCC
	TACTCTCGATTCCTGCTCAGGTACAAGATGACCTGTGAATACACATGGCCCAACCACCTCCTGGGCT
	CCGACAAGGCAGCCGTGAGCGCTCTCCTGGAGCACCACGGGCTGCAGGOGGACGTGGCCTTTGGCCA
	CAGCAAGCTGTTCATCCGCTCACCCCGGACACTGGTCACACTGGAGCAGAGCCCAGCCCGCCTCATC
	CCCATCATTGTGCTGCTATTGCAGAAGGCATGGCGGGGCACCTTGGCGAGGTGGCGCTGCCGGAGGC
	TGAGGGCTATCTACACCATCATGCGCTGGTTCCGGAGACACAAGGTGCGGGCTCACCTGGCTGAGCT
	GCAGCGGCGATTCCAGACTGCAAGGCAGCCGCCACTCTACGGGCGTGACCTTCTGTGGCCGCTGCCC
	CCTGCTGTGCTGCAGCCCTTCCAGGACACCTGCCACGCACTCTTCTGCAGGTGGCGGGCCCGGCAGC
	TGGTGAAAAACATCCCCCCTTCAGACATCCCCCAGATCAAGGCCAAGCTGGCCGCCATGGGGCCCCT
	CCAAGGGCTTCGTCAGGACTGGGGCTGCCGACGGGCCTGGGCCCGAGACTACCTGTCCTCTGCCACT
	GACAATCCCACAGCATCAAGCCTGTTTGCTCAGCGACTAAAGACACTTCGGGACAAAGATGGCTTCG
	GGGCTGTGCTCTTTTCAAGCCATGTCCGCAAGGTGAACCGCTTCCACAAGATCCGGAACCGGGCCCT
	CCTGCTCACAGACCAGCACCTCTACAAGCTGGACCCTGACCGGCAGTACCGGGTGATGCGGGCCGTG
	CCCCTTGAGGCGGTGACGGGGCTGAGCGTGACCAGCGGAGGAGACCAGCTGGTGGTGCTGCACGCCC
	GCGGCCAGGACGACCTCGTGGTGTGCCTGCACCGCTCCCGGCCGCCATTGGACAACCGCGTTGGGGA
	CCTGGTGGGCGTGCTGGCCGCACACTGCCAGGGGGAGGGCCGCACCCTGGAGGTTCGCGTCTCCGAC
	TGCATCCCACTAAGCCATCGCGGGGTCCGGCGCCTCATCTCCGTGGACCCCAGGCCGGAGCAGCCAG
	AGCCCGATTTCCGCTGCGCTCGCGGCTCCTTCACCCTGCTCTGGCCCAGCCGCTGA
	ORE Start: ATG at 15		ORF Stop: TGA at 3069
	SEQ ID NO: 154	1018 aa	MW at 116483.8kD
NOV36b,	MEDEEGPEYGKPDFVLLDQVTMEDFMRNLQLRFEKGRIYTYIGEVLVSVNPYQELPLYGPEAIARYQ
CG59522-02
Protein Sequence	GRELYERPPHLYAVANAAYKAMKYRSRDTCIVISGESGAGKTEASKHIMQYIAAVTNPSQRAEVERV
	KDVLLKSTCVLEAFGNARTNRNHNSSRFGKYNDINFDFKGDPTGGRIHSYLLEKSRVLKQHVGERNF
	HAFYQLLRGSEDKQLHELHLERNPAVYNFTHQGAGLNMTVHSALDSDEQSHQAVTEAMRVIGFSPEE
	VESVHRILAAILHLGNIEFVETEEGGLQKEGLAVAEEALVDHVAELTATPRDLVLRSLLARTVASGG
	RELIEKGHTAAEASYARDACAKAVYQRLFEWVVNRINSVMEPRGRDPRRDGKDTVIGVLDIYGFEVF
	PVNSFEQFCINYCNEKLQQLFIQLILKQEQEEYEREGITWQSVEYFNNATIVDLVERPHRGILAVLD
	EACSSAGTITDRIFLQTLDTHHRHHLHYTSRQLCPTDKTMEFGRDFRIKHYAGDVTYSVEGFIDKNR
	DFLFQDFKRLLYNSTDPTLRAHWPDGQQDITEVTKRPLTAGTLFKNSMVALVENLASKEPFYVRCIK
	PNEDKVAGKLDENHCRHQVAYLGLLENVRVRRAGFASRQFYSRFLLRYKMTCEYTWPNHLLGSDKAA
	VSALLEQHOLQGDVAFGHSKLFIRSPRTLVTLEQSRARLIPITVLLLQKAWRGTLARWRCRRLRAIY
	TIMRWTRRHKVRAHLAELQRRFQAARQPPLYGRDLVWPLPPAVLQPFQDTCHALFCRWRARQLVKNI
	PPSDMPQIKAKVAAMGALQGLRQDWGCRRAWARDYLSSATDNPTASSLFAQRLKTLRDKDGRGAVLF
	SSHVRKVNRFHKIRNRALLLTDQHLYKLDPDRQYRVMRAVPLEAVTGLSVTSGGDQLVVLHARGQDD
	LVVCLHRSRPPLDNRVGELVGVLAAHCQGEGRTLEVRVSDCIPLSHRGVRRLISVEPRPEQPEPDFR
	CARGSFTLLWPSR

[0544] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 36B.

TABLE 36B
Comparison of NOV36a against NOV36b.
			Identities/
			Similarities for
	Protein	NOV36a Residues/	the Matched
	Sequence	Match Residues	Region
	NOV36b	1 . . . 1013	979/1018 (96%)
		1 . . . 1018	982/1018 (96%)

[0545] Further analysis of the NOV36a protein yielded the following properties shown in Table 36C.

TABLE 36C
Protein Sequence Properties NOV36a
PSort             0.8800 probability located in nucleus; 0.3902
analysis:         probability located in microbody (peroxisome);
                  0.2210 probability located in lysosome (lumen);
                  0.1000 probability located in mitochondrial
                  matrix space
SignalP analysis: No Known Signal Sequence Predicted

[0546] 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
			Identities/
			Similarities for
Geneseq	Protein/Organism/Length	NOV36a Residues/	the Matched	Expect
Identifier	[Patent #, Date]	Match Residues	Region	Value
AAU23125	Novel human enzyme	1 . . . 1013	1009/1018 (99%)	0.0
	polypeptide #211 - Homo	9 . . . 1026	1011/1018 (99%)
	sapiens, 1026 aa.
	[WO200155301-A2,
	02 AUG. 2001]
AAU23128	Novel human enzyme	1 . . . 853	851/858 (99%)	0.0
	polypeptide #214 - Homo	9 . . . 866	851/858 (99%)
	sapiens, 909 aa.
	[WO200155301-A2,
	02 AUG. 2001]
ABB71113	Drosophila melanogaster	8 . . . 1012	503/1017 (49%)	0.0
	polypeptide SEQ ID NO	6 . . . 1007	686/1017 (66%)
	40131 -Drosophila
	melanogaster, 1011 aa.
	[WO200171042-A2,
	27 SEP. 2001]
AAM80123	Human protein SEQ ID NO	243 . . . 1011	438/769 (56%)	0.0
	3769 - Homo sapiens, 764	1 . . . 762	570/769 (73%)
	aa. [WO200157190-A2,
	09 AUG. 2001]
AAM79139	Human protein SEQ ID NO	254 . . . 1011	434/758 (57%)	0.0
	1801 - Homo sapiens, 753	1 . . . 751	564/758 (74%)
	aa. [WO200157190-A2,
	09 AUG. 2001]

[0547] 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
			Identities/
Protein			Similarities for
Accession		NOV36a Residues/	the Matched	Expect
Number	Protein/Organism/Length	Match Residues	Portion	Value
Q63357	Myosin I - Rattus norvegicus	1 . . . 1011	606/1011 (59%)	0.0
	(Rat), 1006 aa.	1 . . . 1004	780/1011 (76%)
A53933	myosin I myr 4 - rat, 1006 aa.	1 . . . 1011	604/1011 (59%)	0.0
		1 . . . 1004	778/1011 (76%)
Q96RI6	Unconventional myosin 1G	33 . . . 646	612/619 (98%)	0.0
	valine form - Homo sapiens	1 . . . 619	612/619 (98%)
	(Human), 633 aa (fragment).
Q96RI5	Unconventional myosin 1G	33 . . . 646	611/619 (98%)	0.0
	methonine form - Homo	1 . . . 619	612/619 (98%)
	sapiens (Human), 633 aa
	(fragment).
Q23978	Myosin IA (MIA) (Brush	8 . . . 1012	503/1017 (49%)	0.0
	border myosin IA) (BBMIA) -	6 . . . 1007	686/1017 (66%)
	Drosophila melanogaster
	(Fruit fly), 1011 aa.

[0548] PFam analysis predicts that the NOV36a protein contains the domains shown in the Table 36F.

TABLE 36F
Domain Analysis of NOV36a
	NOV36a	Identities/
Pfam	Match	Similarities for	Expect
Domain	Region	the Matched Region	Value
myosin_head	11 . . . 689	305/747 (41%)	8.1e−288
		531/747 (71%)

Example 37

[0549] 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: 155	3807 bp
NOV37a,	ATGGCGGCGGCGGCGGCGAGCGGAGCTGGCGGGGCTGCCCGGCCCGGGACTGGGGGAGCCGGGCCCG
CG89709-01
DNA Sequence	CGGGCCGCCTGCTGCCTCCGCCCGCGCCGGGGTCCCCAGCCGCCCCCGCTGCCGTGTCCCCTGCGGC
	CGGCCAGCCGCGTCCCCCAGCCCCGGCCTCCCGCGGACCCATGCCCGCCCGTATCGGCTACTACGAG
	ATCGACCGCACCATCGGCAAGGGCAACTTCGCGGTGGTCAAGCGGGCCACGCCCTCGTACACCAAGG
	CCAAGGTTGCTATCAAGATCATAGATAAGACCCAGCTGGATGAAGAAAACTTGAAGAAGATTTTCCG
	GGAAGTTCAAATTATGAAGATGCTTTGCCACCCCCATATCATCAGGCTCTACCACGTTATGGAGACA
	GAACGGATGATTTATCTGGTGACAGAATATGCTAGTGGAGGGGAAATATTTGACCACCTGGTGGCCC
	ATGGTAGAATGGCAGAAAAGGAGGCACGTCGGAAGTTCAAACAGATCGTCACAGCTGTCTATTTTTG
	TCACTGTCGGAACATTGTTCATCGTGATTTAAAAGCTGAAAATTTACTTCTGGATGCCAATCTGAAT
	ATCAAAATAGCAGATTTTGGTTTCAGTAACCTCTTCACTCCTGGCCAGCTCCTGAAGACCTGGTGTG
	GCAGCCCTCCCTATGCTGCACCTGAACTCTTTGAAGGAAAAGAATATGATGGGCCCAAAGTGGACAT
	CTGGAGCCTTGGAGTTGTCCTCTACGTGCTTGTGTGCGGTGCCCTGCCATTTGATGGAAGCACACTG
	CAGAATCTGCGGGCCCGCGTGCTCAGTGGAAAGTTCCGCATCCCATTTTTTATGTCCACAGAATGTG
	AGCATTTGATCCGCCATATGTTGGTGTTAGATCCCAATAAGCGCCTCTCCATGGAGCAGATCTGCAA
	GCACAAGTGGATGAAGCTAGGGGACGCCGATCCCAACTTTGACAGGTTAATAGCTGAATGcCAAcAA
	CTAAAGGAAGAAAGACAGGTCGACCCCCTGAATGAGGATGTCCTCTrGGCCATGGAGGACATGGGAC
	TGCACAAAGAACAGACACTGCAGGCGGAGCAGGCAGGTACTGCTATGAACATCAGCGTTCCCCAGGT
	GCACCTGATCAACCCAGAGAACCAAATTGTGGACCCCGATGGGACACTGAATTTGGACAGTGATGAG
	GGTGAAGAGCCTTCCCCTGAAGCATTGGTGCGCTATTTGTCAATGAGGAGGCACACAGTGGGTGTGG
	CTGACCCACGCACGGAAGTTATGGAAGATCTGCAGAAGCTCCTACCTGGCTTTCCTGGAGTCAACCC
	CCAGGCTCCATTCCTGCAGGTGGCCCCTAATGTGAACTTCATGCACAACCTGTTGCCTATGCAAAAC
	TTGCAACCAACCGGGCAACTTGAGTACAAGGAGCAGTCTCTCCTACAGCCGCCCACGCTACAGcTGT
	TGAATGGAATGGGCCCCCTTGGCCGGAGGCATCAGATGGAGGACCCAACATCCAACTGCATGCCCA
	GCAGCTGCTGAAGCGCCCACGGGGACCCPCTCCGCTTGTCACCATGACACCAOCAGTGCCAGCAGTT
	ACCCCTGTGGACGAGGAGAGCTCAGACGGGGAGCCAGACCAGGAAGCTGTGCAGAGCTCACCTACA
	AGGACTCCAACACTCTGCACCTCCCTACGGAGCGTTTCTCCCCTGTGCGCcGGTTcTcAGATGGGGC
	TGCGAGCATCCAGGCCTTCAAAGCTCACCTCGAAAAAATGGGCAACAACAGCAGCATCAAACAGCTG
	CAGCAGGAGTGTGAGCAGCTGCAGAAGATGTACGGGGGGCAGATTGATGAAAGAACCCTGGAGAAGA
	CCCAGCAGCAGCATATGTTATACCAGCAGGAGCAGCACCATCAAATTCTCCAGCAACAAATTCAAGA
	CTCTATCTGTCCTCCTCAGCCATCTCCACCTCTTCAGGCTGCATGTGAAAATCAGCCAGCCCTCCTT
	ACCCATCAGCTCCAGACGTTAGGATTCAGCCTTCAAGCCCACCCCCCAACCACCCCAACAACCCATC
	TCTTCAGGCAGCCCAGTAATAGTCCTCCCCCCATGAGCAGTGCCATGATCCAGCCTCACGGGGCTGC
	ATCTTCTTCCCAGTTTCAAGGCTTACCTTCCCGCAGTGCAATCTTTCAGCAGCAACCTCAGAACTGT
	TCCTCTCCTCCCAACGTGGCACTAACCTGCTTGGGTATGCAGCAGCCTGCTCAGTCACAGCAGGTCA
	CCATCCAAGTCCAAGAGCCTGTTGACATGCTCAGCAACATGCCAGGCACAGCTGCAGGCTCCAGTGG
	GCGCGGCATCTCCATCAGCCCCAGTGCTGGTCAGATGCAGATGCAGCACCGTACCAACCTGATGGCC
	ACCCTCAGCTATGGGCACCGTCCCTTGTCCAAGCAGCTGAGTGCTGACAGTGCAGAGGCTCACAGTG
	CACATCAGCAGCCGCCACACTATACCACGTCGGCACTACAGCAGGCCCTGCTGTCTCCCACGCCGCC
	AGACTATACAAGACACCAGCAGGTACCCCACATCCTTCAAGGACTGCTTTCTCCCCGGCATTCGCTC
	ACCGGCCACTCGGACATCCGGCTGCCCCCAACAGAGTTTGCACAGCTCATTAAAAGGCAGCAGCAAC
	AACGGCAGCAGCAGCAGCAACAGCAGCAACAGCAAGAATACCAGGAACTGTTCAGGCACATGAACCA
	AGGGGATGCGGGGAGTCTGGCTCCCAGCCTTGGGGGACAGAGCATGACAGAGCGCCAGGCTTTATCT
	TATCAAAATGCTGACTCTTATCACCACACGATCCACAACAGCCACGATGCTTATGTACAGCTGGATA
	ACTTGCCAGGAATGAGTCTCGTGGCTGGGAAAGCACTTAGCTCTGCCCGGATGTCGGATGCAGTTCT
	CAGTCAGTCTTCGCTCATGGGCAGCCAGCAGTTTCAGGATGGGGAAAATGAGGAATGTGGGGCAAGC
	CTGGGAGGTCATGAGCACCCAGACCTGAGTGATGGCAGCCAGCATTTAAACTCCTCTTGCTATCCAT
	CTACGTGTATTACAGACATTCTGCTCAGCTACAAGCACCCCGAAGTCTCCTTCAGCATGGAGCAGGC
	AGGCGTGTAACAAGAAACAGAGAGAGAGCAAGAGGTCCCGAGTCCCCTCCTAGTCTTTCATCCTCAA
	TTTGCACAGAGGAAAGCGGGTGCCCGGCATGGCCATCCTGATGTTGCTGGCGGGATCCCCATGCACC
	TTGTCCTTCTCCACTGATACTCGCAGCTCGGCTCCTGGACCCAAGATCCCTTGAGTGGAATTCTGCA
	GTGCAAGAGCCCTTCGTGGGAGCTGTCCCATGTTTCCATGGTCCCCAGTCTCCCCTCCACTTGGTCG
	GGTCACCAACTACTCACCAGAAGGGGGCTTACCAAGAAAGCCCTAAAAAGCTGTTGACTTATCTGCG
	CTTGTTCCAACTCTTATGCCCCCAACCTGCCCTACCACCACCACGCGCTCAGCCTGATGTGTTTACA
	TGGTACTGTATGTATGGGAGAGCAGACTGCACCCTCCAGCAACAACAGATGAAAGCCAGTGAGCCTA
	CTAACCGTGCCATCTTGCACAACTACACTTTAAAAAAACTCATTGCTTTGTATTGTAGTAACCAATA
	TGTCCAGTATACGTTGAATGTATATGAACATACTTTCCTATTTCTGTTCTPTGAAAATGTCAGAAAT
	ATTTTTTTCTTTCTCATTTTATGTTGAACTAAAAAGGATTAAAAAAAAATCTCC
	ORF Start: ATG at 1		ORF Stop: TAA at 3157
	SEQ ID NO: 156	1052 aa	MW at 115587.7kD
NOV37a,	MAAAAASGAGGAAGAGTGGAGPAGRLLPPPAPGSPAAPAAVSPAAGQPRPPAPASRGPMPARIGYYE
CG89709-01
Protein Sequence	IDRTIGKGNFAVVKRATHLVTKAXVAIKIIDKTQLDEENLKRIFREVQIMKMLCHPHIIRLYQVMET
	ERMIYLVTEYASGGEIFDHLVAHGRMAEKEARRKFKQIVTAVYFCHCRNIVHRDLKAENLLLDANLN
	IKIADFGFSNLFTPGQLLKTWCGSPPYAAPELFEGKEYDGPKVDIWSLGVVLYVLVCGALPFDGSTL
	QNLRARVLSGKFRIPFFMSTECEHLIRHMLVLDPNKRLSMEQICKHKWMKLGDADPNFDRLIAECQQ
	LKEERQVDPLNEDVLLAMEDMGLDKEQTLQAEQAGTAMNISVPQVQLINPENQIVEPDGTLNLDSDE
	GEEPSPEALVRYLSMRRHTVGVADPRTEVMEDLQKLLPGFPGVNPQAPFLQVAPNVNFMHNLLPMQN
	LQPTGQLEYKEQSLLQPPTLQLLNGMGPLGRRASDGGANIQLHAQQLLKRPRGPSPLVTMTPAVPAV
	TPVDEESSDGEPDQEAVQSSTYKDSNTLHLPTERFSPVRRFSDGAASIQAFKAHLEKMGNNSSIKQL
	QQECEQLQKMYGGQIDERTLEKTQQQHMLYQQEQHHQILQQQIQDSICPPQPSPPLQAACENQPALL
	THQLQRLRIQPSSPPPNHPNNHLFRQPSNSPPPMSSAMIQPHGAASSSQFQGLPSRSAIFQQQPENC
	SSPPNVALTCLGMQQPAQSQQVTIQVQEPVDMLSNMPGTAAGSSGRGISISPSACQMQMQHRTNLMA
	TLSYGHRPLSKQLSADSAEAHSAHQQPPNYTTSALQQALLSPTPPDYTRHQQVPHILQGLLSPRHSL
	TGIISDIRLPPTEFAQLIKRQQQQRQQQQQQQQQQEYQELFRHMNQGDAGSLAPSLGGQSMTERQALS
	YQNADSYHHTIQNSDDAYVQLDNLPGMSLVAGKALSSARMSDAVLSQSSLMGSQQFQDGENEEcGAs
	LGGHEHFDLSDGSQHLNSSCYPSTC ITDILLSYKHPEVSFSMEQAGV
	SEQ ID NO: 157	3987 bp
NOV37b,	ATGGCGGCGGCGGCGGCGAGCGGAGCTGGCGGGGCTGCCGGGGCCGGGACTGGGGGAGCCGGGCCCG
CG89709-02
DNA Sequence	CGGGCCGCCTGCTGCCTCCGCCCGCGCCGGGGTCCCCAGCCGCCCCCGCTGCCGTGTCCCCTGCGGC
	CGGCCAGCCGCGTCCCCCACCCCCGGCCTCCCGCGGACCCATGCCCGCCCGTATCGGCTACTACGAG
	ATCGACCGCACCATCGGCAAGGGCAACTTCGCGGTGGTCAAGCGGGCCACGCACCTCGTCACCAAGG
	CCAAGGTTGCTATCAAGATCATAGATAAGACCCAGCTGGATGAAGAAAACTTGAAGAAGATTTTCCG
	GGAAGTTCAAATTATGAAGATGCTTTGCCACCCCCATATCATCAGGCTCTACCAGGTTATGGAGACA
	GAACGGATGATTTATCTGGTGACAGAATATGCTAGTGGAGGGGAAATATTTGACCACCTGGTGGCCC
	ATGGTACAATGGCACAAAAGGAGGCACGTCGGAAGTTCAAACAGATCGTCACAGCTGTCTATTTTTG
	TCACTGTCCGAACATTGTTCATCGTGATTTAAAAGCTGAAAATTTACTTCTGGATGCCAATCTGAAT
	ATCAAAATAGCAGATTTTGGTTTCAGTAACCTCTTCACTCCTCGGCAGCTGCTGAAGACCTGGTGTG
	GCAGCCCTCCCTATGCTGCACCTGAACTCTTTGAAGGAAAAGAATATGATGGGCCCAAAGTGGACAT
	CTGGAGCCTTGGAGTTGTCCTCTACGTGCTTGTGTGCGGTGCCCTGCCATTTGATGGAAGCACAcTG
	CAGAATCTGCGGGCCCGCGTGCTGAGTGGAAAGTTCCGCATCCCATTTTTTATGTCCACAGAATGTG
	AGCATTTGATCCGCCATATGTTGGTGTTAGATCCCAATAAGCGCCTCTCCATGGAGCAGATcTGc~
	GCACAAGTCGATGAACCTAGCGGACGCCGATCCCAACTTTGACAGGTTAATAGCTGAATGCCAACAA
	CTAAAGGAAGAAAGACAGGTGGACCCCCTGAATGAGGATGTCCTCTTGOCCATGGAGGACATGGGAC
	TCGACAAAGAACAGACACTGCAGGCGGAGCACGCAGGTACTGCTATGAACATCAGCGTTCCCCAGGT
	GCAGCTGATCAACCCAGAGAACCAAATTGTGGAGCCGGATCGGACACTGAATTTGGACAGTGATGAC
	CGTGAAGAGCCTTCCCCTGAAGCATTCCTGCGCTATTTGTCAATGAGGAGGCACACAGTGGGTGTGG
	CTGACCCACGCACGGAAGTTATGGAAGATCTGCAGAAGCTCCTACCTGGCTTTCCTGGAGTCAACCc
	CCAGGCTCCATTCCTGCAGGTGGCCCCTAATGTGAACTTCATGCACAACCTGTTGCCTATGCAAAAC
	TTGCAACCAACCGGGCAACTTGAGTACAAGGACCAGTCTCTCCTACAGCCGCCCACGCTACAGCTGT
	TGAATGGAATGGGCCCCCTTGGCCGGAGGGCATCAGATGGAGGAGCCAACATCCAACTGCATGCCCA
	GCAGCTGCTGAAGCGCCCACGCGGACCCTCTCCGCTTGTCACCATGACACCA~CAGTGCCAGCAGTT
	ACCCCTGTGGACGAGGAGAGCTCAGACCGGGAGCCAGACCAGGAAGCTGTGCAGAGCTCTACCTAcA
	AGGACTCCAACACTCTGCACCTCCCTACGGAGCGTTTCTCCCCTGTGCGCCGGTTCTCAGATGGGGC
	TGCGAGCATCCAGGCCTTCAAAGCTCACCTGCAAAAAATGGGCAACAACAGCAGCATCAAACAGCTG
	CAGCAGGAGTGTGAGCAGCTGCAGAAGATGTACGGGGGGCAGATTGATGAAAGAACCCTGGAGAAGA
	CCCAGCAGCAGCATATGTTATACCAGCAGGAGCAGCACCATCAAATTCTCCAGCAACAAATTC~GA
	CTCTATCTGTCCTCCTCAGCCATCTCCACCTCTTCAGGCTGCATGTGAAAATCAGCCAGCCCTCCTT
	ACCCATCAGCTCCAGAGGTTAAGGATTCAGCCTTCAAGCCCACCCCCCAACCACCCCAACAACCATC
	TCTTCAGGCAGCCCAGTAATAGTCCTCCCCCCATGAGCAGTGCCATGATCCAGCCTCACOGGGCTGC
	ATCTTCTTCCCAGTTTCAAGGCTTACCTTCCCGCAGTGCAATCTTTCAGCAGCAACCTGAGAACTGT
	TCCTCTCCTCCCAACGTGGCACTAACCTGCTTGGGTATGCAGCAGCCTGCTCAGTCACAGCAGGTCA
	CCATCCAAGTCCAAGAGCCTGTTGACATGCTCAGCAACATGCCAGGCACAGCTGCAGGCTCCAGTGG
	GCGCGGCATCTCCATCAGCCCCAGTGCTGGTCAGATGCAGATGCAGCACCGTACCAACCTGATGGCC
	ACCCTCAGCTATGGGCACCGTCCCTTGTCCAAGCAGCTGAGTGCTGACAGTGCAGACGCTCACAGCT
	TGAACGTGAATCGGTTCTCCCCTGCTAACTACGACCAGGCGCATTTACACCCCCATCTGTTTTCGGA
	CCAGTCCCGGGGTTCCCCCAGCAGCTACAGCCCTTCAACAGGAGTGGGGTTCTCTCCAACCCAAGCC
	CTGAAAGTCCCTCCACTTGACCAATTCCCCACCTTCCCTCCCACTGCACATCAGCAGCCGCCACACT
	ATACCACGTCGGCACTACAGCAGGCCCTGCTGTCTCCCACGCCGCCAGACTATACAAGACACcAGCA
	GGTACCCCACATCCTTCAAGGACTGCTTTCTCCCCGGCATTCGCTCACCGGCCACTCGGACATCCGG
	CTGCCCCCAACAGAGTTTGCACAGCTCATTAAAAGGCAGCAGCAACAACGGCAGCAGCAGCAGCAAC
	AGCAGCAACAGCAAGAATACCAGGAACTGTTCAGGCACATGAACCAAGGGGATGCGGGGAGTCTGGC
	TCCCAGCCTTGGGGGACAGAGCATGACAGAGCGCCAGGCTTTATCTTATCAAAGTGCTGACTCTTAT
	CACCACACGATCCAGAACAGCGACGATGCTTATGTACAGCTGGATAACTTCCCAGGAATGAGTCTCG
	TGGCTGGGAAAGCACTTAGCTCTCCCCGGATGTCGGATGCAGTTCTCAGTCAGTCTTCGCTCATGGG
	CAGCCAGCAGTTTCAGGATGGGGAAAATGAGGAATGTGGGGCAAGCCTGGGAGGTCATGAGCACCCA
	GACCTGAGTGATCGCAGCCAGCATTTAAACTCCTCTTGCTATCCATCTACGTGTATTACAGACATTC
	TGCTCAGCTACAAGCACCCCGAAGTCTCCTTCAGCATGGAGCAGGCAGGCGTGTAACAAGAAACAGA
	GAGAGAGCAAGAGGTCCCGAGTCCCCTCCTAGTCTTTCATCCTGAATTTGCACAGAGGAAAGCGGGT
	GCCCGGCATGGCCATCCTGATGTTGCTGGCGGGATCCCCATGCACCTTGTCCTTCTCCACTGATACT
	GGCAGCTCGGCTCCTGGACCCAAGATCCCTTGAGTGCAATTCTGCAGTGCAAGAGCCCTTCGTGAGA
	GCTGTCCCATGTTTCCATGGTCCCCAGTCTCCCCTCCACTTGGTGGGGTCACCAACTACTCACCAGA
	AGGGGGCTTACCAAGAAAGCCCTAAAAAGCTGTTGACTTATCTGCGCTTGTTCCAACTCTTATGCCC
	CCAACTGCCCTTACCACCACCACGCGCTCAGCCTGATGTGTTTACATGGTACTGTATGTATGGGAGA
	GCAGACTGCACCCTCCAGCAACAACAGATGAAAGCCAGTGAGCCTACTAACCGTGCCATCTTGCAAA
	CTACACTTTAAAAAAAACTCATTGCTTTGTATTGTAGTAACCAATATGTGCAGTATACGTTGAATGT
	ATATGAACATACTTTCCTATTTCTGTTCTTTGAAAATGTCAGAAATATTTTTTTCTTTCTCATTTTA
	TGTTGAACTAAAAAGGATTAAAAAAAAAATCTCC
	ORF Start: ATG at 1		ORF Stop: TAA at 3337
	SEQ ID NO: 158	1112 aa	MW at 122094.8kD
NOV37b,	MAAAAASGAGGAAGAGTGGAGPAGRLLPPPAPGSPAAPAAVSPAAGQPRPPAPASRGPMPARIGYYE
CG89709-02
Protein Sequence	IDRTIGKGNFAVVKRATHLVTKAKVAIKIIDKTQLDEENLKKIFREVQIMKMLCHPHIIRLYQVMET
	ERMIYLVTEYASGGEIFDHLVAHGRMAEKEARRKFKQIVTAVYFCHCRNIVHRDLKAENLLLDANLN
	IKIADFGFSNLFTPGQLLKTWCGSPPYAAPELFEGKEYDGPKVDIWSLGVVLYVLVCGALPFDGSTL
	QNLRARVLSGKFRIFFFMSTECEHLIRHMLVLDPNKRLSMEQICKHKWMKLGDADPNFDRLIAECQQ
	LKEERQVDPLNEDVLLAMEDMGLDKEQTLQAEQAGTAMNISVPQVQLINPENQIVEPDGTLNLSKDE
	GEEPSPEALVRYLSMRRHTVGVADPRTEVMEDLQKLLPGFPGVNPQAPFLQVAPNVNFMHNLLPMQU
	DLSDGSQHLNSSCYPSTCITDILLSYKHPEVSFSMEQAGV
	SEQ ID NO: 159	4889 bp
NOV37c,	TTGAACTGGGACAGAGGTCACAGCAGAGGTCACATTGGCGATTCGAGCGGCGGTCGGGGGTTGGCTT
CG89709-03
DNA Sequence	TCGGTCGGGCATCCTGCGCCCCCCACTCGGGAAACGTGGCGGAGACTTCCAGGTTGGGGGCCCATCG
	AACGTTCCCACCGCCAGCTCCCGGAGGGGGGCACCCGGGAGCCAGCGCCTCAGGAACCGGGGCCCAC
	GCGGGAAGGTCGAGCCCGCCGGTGAGGTCACGGTTGCCATGGCTCCGGGCAGTGACGCGCGTCGGCA
	CGTGACCCGCGGTTGCCATGGAGCCGGGCGCCGGTCGGCGAAAGCGCCCCGCCTCCCCGAGTGACGT
	CCGCGGCCCCCCCTTTCCCGCCCCCCCTTGCCCCCTCCCCCGAGCCGGCTCCCCGCGGCCCCGGAGC
	TTTCACTGCACAACAAGATGGCGGCGGCGGCGGCGAGCGGAGCTGGCQGGGCTGCCGGGGCCGGGAC
	TGGGGGAGCCGGGCCCGCGGGCCCCCTGCTGCCTCCGCCCGCGCCGGGGTCCCCAGCCGCCCCCGCT
	GCCGTGTCCCCTGCGGCCGGCCAGCCGCGTCCCCCAGCCCCGGCCTCCCGCCGACCCATGCCCGCCC
	GTATCGGCTACTACGAGATCGACCGCACCATCGGCAAGGGCAACTTCGCGGTGGTCAAGCGGGCCAC
	GCACCTCGTCACCAAGGCCAAGGTTGCTATCAAGATCATAGATAAGACCCAGCTCGATGAAGAAAAC
	TTGAAGAAGATTTTCCGGGAAGTTCAAATTATGAAGATGCTTTGCCACCCCCATATCATCACGCTCT
	ACCAGGTTATGGAGACAGAACGGATGATTTATCTCGTGACAGAATATGCTAGTGGAGGGGAAATATT
	TGACCACCTGGTGGCCCATGGTAGAATGGCAGAAAAGGAGGCACGTCGGAAGTTCAAACAGATCGTC
	ACAGCTGTCTATTTTTGTCACTGTCGGAACATTGTTCATCGTGATTTAAAAGCTGAAAATTTACTTC
	TGGATGCCAATCTGAATATCAAAATAGCAGATTTTGGTTTCAGTAACCTCTTCACTCCTGGGCAGCT
	GCTGAAGACCTGGTGTGGCAGCCCTCCCTATGCTGCACCTGAACTCTTTGAAGGAAAAGAATATGAT
	GGGCCCAAAGTGGACATCTGGAGCCTTGGAGTTGTCCTCTACGTGCTTGTCTGCGGTGCCCTGCCAT
	TTGATGGAAGCACACTGCAGAATCTGCGGGCCCGCGTGCTGAGTGGAAAGTTCCGCATCCCATTTTT
	TATGTCCACAGAATGTGAGCATTTGATCCGCCATATGTTGGTGTTAGATCCCAATAAGCGCCTCTCC
	ATGGAGCAGATCTGCAAGCACAAGTGGATTAAGCTAGGGGACGCCCATCCCAACTTTGACAGGTTAA
	TAGCTGAATGCCAACAACTAAACGAAGAAAGACACGTCGACCCCCTGAATGAGGATGTCCTCTTGGC
	CATGGAGGACATGGGACTGGACAAAGAACAGACACTCCAGGCGGAGCAGGCAGGTACTGCTATGAAC
	ATCAGCGTTCCCCAGGTGCAGCTGATCAACCCAGAGAACCAAATTGTGGAGCCCGATGGGACACTGA
	ATTTGGACAGTGATGAGGGTGAAGAGCCTTCCCCTGAAGCATTGGTGCGCTATTTGTCAATGAGGAG
	GCACACAGTGGGTGTGGCTGACCCACCCACGGAAGTTATGGAAGATCTGCAGAAGCTCCTACCTGGC
	TTTCCTGGAGTCAACCCCCAGGCTCCATTCCTGCAGGTGGCCCCTAATGTGAACTTCATGCACAACC
	TGTTGCCTATGCAAAACTTGCAACCAACCGGGCAACTTGAGTACAAGGAGCAGTCTCTCCTACAGCC
	GCCCACGCTACAGCTGTTGAATGGAATGGGCCCCCTTGGCCGGAGCGCATCAGATGGAGGAGCCAAC
	ATCCAACTGCATGCCCAGCAGCTGCTGAAGCGCCCACGGGGACCCTCTCCGCTTGTCACCATGACAC
	CAGCAGTGCCAGCAGTTACCCCTGTGGACGAGGAGAGCTCAGACGGGGAGCCAGACCAGGAAGCTGT
	GCAGAGCTCTACCTACAAGGACTCCAACACTCTGCACCTCCCTACGGAGCGTTTCTCCCCTGTGCGC
	CGGTTCTCAGATGGGGCTGCGAGCATCCAGGCCTTCAAAGCTCACCTGGAAAAAATGGGCAACAACA
	GCAGCATCAAACAGCTGCAGCAGGAGTGTGAGCAGCTGCAGAAGATGTACGGGGGGCAGATTGATGA
	AAGAACCCTGGAGAAGACCCAGCAGCAGCATATGTTATACCAGCAGGAGCAGCACCATCAAATTCTC
	CAGCAACAAATTCAAGACTCTATCTGTCCTCCTCAGCCATCTCCACCTCTTCAGGCTGCATGTGAAA
	ATCAGCCAGCCCTCCTTACCCATCAGCTCCAGAGGTTAAGGATTCAGCCTTCAAGCCCACCCCCCAT
	CCACCCCAACAACCATCTCTTCAGGCAGCCCAGTAATAGTCCTCCCCCCATGAGCAGTGCCATGATC
	CAGCCTCACGGGGCTGCATCTTCTTCCCAGTTTCAAGGCTTACCTTCCCGCAGTGCAATCTTTCAGC
	AGCAACCTGAGAACTGTTCCTCTCCTCCCAACGTGGCACTAACCTGCTTGGGTATGCAGCAGCCTGC
	TCAGTCACAGCAGGTCACCATCCAAGTCCAAGACCCTGTTGACATGCTCAGCAACATGCCAGGCACA
	GCTGCACGCTCCAGTGGGCGCGGCATCTCCATCAGCCCCAGTGCTGGTCAGATGCAGATGCAGCACC
	GTACCAACCTGATGGCCACCCTCAGCTATGGGCACCGTCCCTTGTCCAAGCAGCTGAGTGCTGACAG
	TGCAGAGGCTCACAGCTTGAACGTGAATCGGTTCTCCCCTGCTAACTACGACCAGGCGCATTTACAC
	CCCCATCTGTTTTCGGACCAGTCCCGCGGTTCCCCCAGCAGCTACAGCCCTTCAACAGGAGTGGGGT
	TCTCTCCAACCCAAGCCCTGAAAGTCCCTCCACTTGACCAATTCCCCACCTTCCCTCCCAGTGCACA
	TCAGCAGCCGCCACACTATACCACGTCGGCACTACAGCAGGCCCTGCTGTCTCCCACGCCGCCAGAC
	TATACAAGACACCAGCAGGTACCCCACATCCTTCAAGGACTGCTTTCTCCCCGGCATTCGCTCACCG
	GCCACTCGGACATCCGGCTGCCCCCAACAGAGTTTGCACAGCTCATTAAAAGGCAGCAGCAACAACG
	GCAGCAGCAGCAGCAACAGCAGCAACAGCAAGAATACCAGGAACTCTTCAGGCACATGAACCAAGGG
	GATGCGGGGAGTCTGGCTCCCAGCCTTGGGGGACAGAGCATGACAGAGCGCCAGGCTTTATCTTATC
	AAAATGCTGACTCTTATCACCATCACACCAGCCCCCAGCATCTGCTACAAATCAGGGCACAAGAATG
	TGTCTCACAGGCTTCCTCACCCACCCCGCCCCACGGGTATGCTCACCAGCCGGCACTGATGCATTCA
	GAGAGCATGGAGGAGGACTGCTCGTGTGAGGGGGCCAAGGATGGCTTCCAAGACAGTAAGAGTTCAA
	GTACATTGACCAAAGGTTGCCATGACAGCCCTCTGCTCTTGAGTACCGGTGGACCTGGGGACCCTGA
	ATCTTTGCTAGGAACTGTGAGTCATGCCCAAGAATTGGGGATACATCCCTATGGTCATCAGCCAACT
	GCTGCATTCAGTAAAAATAAGGTGCCCAGCAGAGAGCCTGTCATACGGAACTGCATGGATAGAAGTT
	CTCCAGGACAAGCAGTGGAGCTGCCGGATCACAATGGGCTCGGGTACCCAGCACGCCCCTCCGTCCA
	TCAGCACCACAGGCCCCGGGCCCTCCAGAGACACCACACGATCCAGAACAGCGACGATGCTTATGTA
	CAGCTGGATAACTTGCCAGGAATGAGTCTCGTGGCTGGGAAAGCACTTACCTCTGCCCGGATGTCGG
	ATGCAGTTCTCAGTCAGTCTTCGCTCATGGGCAGCCAGCAGTTTCAGGATGGGGAAAATGAGGAATG
	TGGGGCAAGCCTGGGAGGTCATGAGCACCCAGACCTGAGTGATGGCAGCCAGCATTTAAACTCCTCT
	TGCTATCCATCTACGTGTATTACAGACATTCTGCTCAGCTACAAGCACCCCGAAGTCTCCTTCAGCA
	TGGAGCAGCCAGGCGTGTAACAAGAAACAGAGAGAGAGCAAGAGGTCCCGAGTCCCCTCCTAGTCTT
	TCATCCTGAATTTGCACAGAGGAAAGCGGGTGCCCGGCATGOCCATCCTGATGTTGCTGGCGGGATC
	GCCATGCACCTTGTCCTTCTCCACTGATACTGGCACCTCGGCTCCTGGACCCAAGATCCCTTGAGTC
	GAATTCTGCAGTGCAAGAGCCCTTCGTGGGAGCTGTCCCATGTTTCCATGGTCCCCAGTCTCCCCTC
	CACTTGGTGGGGTCACCAACTACTCACCAGAAGGGGGCTTACCAAGAAAGCCCTAAAAAGCTGTTGA
	CTTATCTGCGCTTGTTCCAACTCTTATGCCCCCAACCTGCCCTACCACCACCACGCGCTCAGCCTGT
	TGTGTTTACATGGTACTGTATGTATGGGAGAGCAGACTGCACCCTCCAGCAACAACAGATGAAAGCC
	AGTGAGCCTACTAACCGTGCCATCTTGCAAACTACACTTTAAAAAAAACTCATTGCTTTGTATTGTA
	GTAACCAATATGTGCAGTATACGTTGAATGTATATGAACATACTTTCCTATTTCTGTTCTTTGAAAG
	TGTCAGAAATATTTTTTTCTTTCTCATTTTATGTTGAACTAAAAAGGATTAAAAAAAAAATCTCC
	ORF Start: ATG at 420		ORF Stop: TAA at 4239
	SEQ ID NO: 160	1273 aa	MW at 139385.7kD
NOV37c,	MAAAAASGAGGAAGAGTGGAGPAGRLLPPPAPGSPAAPAAVSPAAGQPRPPAPASRGPMPARIGYYE
CG89709-03
Protein Sequence	IDRTIGKGNFAVVKRATHLVTKAKVAIKIIDKTQLDEENLKKIFREvQIMKMLCHPHIERLYQVMET
	ERMIYLVTEYASGGEIFDHLVAHGRNAEKEARRKFKQIVTAVYFCNCRNIVHRDLKAENLLLDANLN
	IKIADFGFSNLFTPGQLLKTWCGSPPYAAPELFEGKEYDGPKVDIWSLGVVLYVLVCGALPEDGSTL
	QNLRARVLSGKFRIPFFMSTECEHLIRHMLVLDPNKRLSMEQICKHKTHKLGDADPNFDRLIAECQQ
	LKEERQVDPLNEDVLLAMEDMGLDKEQTLQAEQAGTAMNISVPQVQLINPENQIVEPDGTLNLDSDE
	GEEPSPEALVRYLSMRRHTVGVADPRTEVMEDLQKLLPGFPGVNPQAPFLQVAPNVNFMHNLLPMQN
	LQPTGQLEYKEQSLLQPPTLQLLNGMGPLGRRASDGGANIQLHAQQLLKRPRGPSPLVTNTPAVPAV
	TPVDEESSDGEPDQEAVQSSTYKDSNTLHLPTERFSPVRRFSDGAASIQAFKAHLEKMGNNSSIKQL
	QQECEQLQKMYGGQIDERTLEKTQQQHMLYQQEQHHQILQQQIQDSICPPQFSPFLQAACENQPALL
	TEQLQRLRIQPSSPPPNHPNNHLFRQPSNSPPPMSSAMIQPHGAASSSQFQGLPSRSAIFQQQPENC
	SSPPNVALTCLGMQQPAQSQQVTIQVQEPVDMLSNMPGTAAGSSGRGISISPSAGQMQMQHRTNLMA
	TLSYGHRPLSKQLSADSAEAHSLNVNRFSPANYDQAHLHPHLFSDQSRGSPSSYSPSTGVGFSPTQA
	LKVPPLDQFPTFPPSAHQQPPHYTTSALQQALLSPTPPDYTRHQQVPHILQGLLSPRHSLTGHSDIR
	LPPTEFAQLIKRQQQQRQQQQQQQQQQEYQELFRBMNQGDAGSLAPSLGGQSMTERQALSYQNADSY
	HHHTSPQHLLQIRAQECVSQASSPTPPHGYAHQPALMHSESMEEDCSCEGAKDGFQDSKSSSTLTKG
	CHDSPLLLSTGGPGDPESLLGTVSHAQELGIHPYGHQPTAAFSKNXVPSREPVIGNCMDRSSPGQAV
	ELPDHNGLGYPARPSVHEHHRPRALQRHHTIQNSDDAYVQLDNLPGMSLVAGKALSSARMSDAVLSQ
	SSLMGSQQFQDGENEECGASLGGHEHPDLSDGSQHLNSSCYPSTCITDILLSYKUPEVSFSMEQAGV
	SEQ ID NO: 161	5033 bp
NOV37d,	TTGAACTGGGACACAGGTCACACCAGAGGTCACATTGGCGATTCGACCGGCGGTGCGGGGTTGGCTT
CG89709-04
DNA Sequence	TGGGTCGGGCATCCTGCGCCCCCCACTCGGGAAAGGTGGCGGAGACTTCGAGGTTGGGGGCCCATCG
	AAGGTTCCCACCGCCAGCTCCCGGAGGGGGGCACCCGGGAGCCAGCGCCTCAGGAACCGGGGCCCAC
	GCGGGAAGGTCGAGCCCGCCGGTGAGGTCACCGTTGCCATGGCTCCGGGCAGTGACGCGCGTCGGCA
	CGTGACCCGCGGTTGCCATGGAGCCGGGCGCCGGTCGGCGAAAGCGCCCCGCCTCCCCGAGTGACGT
	CCGCGGCCCCCCCTTTCCCGCCCCCCCTTGCCCCCTCCCCCGAGCCGGCTCCCCGCGGCCCCGGAGG
	TTTCACTGCACAACAAGATGGCGGCGGCGGCGGCGAGCGGAGCTGGCGGGGCTGCCGGGGCCGGGAC
	TGGGGGAGCCGGGCCCGCGGGCCGCCTGCTGCCTCCGCCCGCGCCGGGGTCCCCAGCCGCCCCCGCT
	GCCGTGTCCCCTGCGGCCGGCCAGCCGCGTCCCCCAGCCCCGGCCTCCCGCGGACCCATGCCCGCCC
	GTATCGGCTACTACGAGATCGACCGCACCATCGGCAAGGGCAACTTCGCGGTGGTCAAGCGGGCCAC
	GCACCTCGTCACCAAGGCCAAGGTTGCTATCAAGATCATAGATAAGACCCAGCTGGATGAAGAAAAC
	TTGAAGAAGATTTTCCGGGAAGTTCAAATTATGAAGATGCTTTGCCACCCCCATATCATCAGGCTCT
	ACCAGGTTATGGAGACAGAACGGATGATTTATCTGGTGACAGAATATGCTAGTGGAGGGGAAATATT
	TGACCACCTGGTGGCCCATGGTAGAATGGCAGAAAAGGAGGCACGTCGGAAGTTCAAACAGATCGTC
	ACAGCTGTCTATTTTTGTCACTGTCGGAACATTGTTCATCGTGATTTAAAACCTGAAAATTTACTTC
	TGGATGCCAATCTGAATATCAAAATAGCAGATTTTGGTTTCAGTAACCTCTTCACTCCTCGGCAGCT
	GCTGAAGACCTGGTGTGGCAGCCCTCCCTATGCTCCACCTGAACTCTTTGAAGGAAAAGAATATGAT
	GGGCCCAAAGTGGACATCTGGACCCTTGGAGTTGTCCTCTACGTGCTTGTGTGCGGTGCCCTGCCAT
	TTGATGGAAGCACACTGCAGAATCTGCGGGCCCGCGTGCTGAGTGGAAAGTTCCGCATCCCATTTTT
	TATGTCCACAGAATGTGAGCATTTGATCCGCCATATGTTGGTGTTAGATCCCAATAAGCGCCTCTCC
	ATGGAGCAGATCTGCAAGCACAAGTGGATGAAGCTAGGGGACGCCGATCCCAACTTTGACAGGTTAA
	TAGCTGAATGCCAACAACTAAAGGAAGAAAGACAGGTGGACCCCCTGAATGAGGATGTCCTCTTGGC
	CATGGAGGACATGGGACTGGACAAAGAACAGACACTGCAGTCATTAAGATCAOATGCCTATGATCAC
	TATAGTGCAATCTACAGCCTGCTGTGTGATCGACATAAGAGACATAAAACCCTGCGTCTCGGAGCAC
	TTCCTAGCATGCCCCOAGCCCTGGCCTTTCAAGCACCAGTCAATATCCAGGCGGAGCAGGCAGGTAC
	TGCTATGAACATCAGCGTTCCCCAGGTGCAGCTGATCAACCCAGAGAACCAAATTGTGGAGCCGGAT
	GGGACACTGAATTTGGACAGTGATGAGGGTGAAGAGCCTTCCCCTGAAGCATTGGTGCGCTATTTGT
	CAATGAGGAGCCACACAGTGGGTGTGGCTGACCCACGCACGGAAGTTATGGAAGATCTGCAGAAGCT
	CCTACCTGGCTTTCCTGGAGTCAACCCCCAGGCTCCATTCCTGCAGGTGGCCCCTAATGTGAACTTC
	ATGCACAACCTGTTGCCTATGCAAAACTTGCAACCAACCGGGCAACTTGAGTACAAGGAGCAGTCTC
	TCCTACAGCCGCCCACGCTACAGCTGTTGAATGGAATGGGCCCCCTTGGCCGGAGGGCATCAGATGG
	AGGAGCCAACATCCAACTGCATGCCCAGCAGCTGCTGAAGCGCCCACGGGGACCCTCTCCGCTTGTC
	ACCATGACACCAGCAGTGCCAGCAGTTACCCCTGTGGACGAGGAGAGCTCAGACGGGGAGCCAGACC
	AGGAAGCTGTGCAGAGCTCTACCTACAAGGACTCCAACACTCTGCACCTCCCTACGGAGCGTTTCTC
	CCCTGTGCGCCGGTTCTCAGATGGGGCTGCGAGCATCCAGGCCTTCAAAGCTCACCTGGAAAAAATG
	GGCAACAACAGCAGCATCAAACAGCTGCAGCAGGAGTGTGAGCAGCTGCAGAAGATGTACGGGGGGC
	AGATTGATGAAAGAACCCTGGAGAAGACCCAGCAGCAGCATATGTTATACCAGCAGGAGCAGCACCA
	TCAAATTCTCCAGCAACAAATTCAAGACTCTATCTGTCCTCCTCAGCCATCTCCACCTCTTCAGGCT
	GCATGTGAAAATCAGCCAGCCCTCCTTACCCATCAGCTCCAGAGGTTAAGGATTCAGCCTTCAAGCC
	CACCCCCCAACCACCCCAACAACCATCTCTTCAGGCAGCCCAGTAATAGTCCTCCCCCCATGAGCAG
	TGCCATGATCCAGCCTCACGGGGCTGCATCTTCTTCCCAGTTTCAAGGCTTACCTTCCCGCACTCCA
	ATCTTTCAGCAGCAACCTGAGAACTGTTCCTCTCCTCCCAACGTGGCACTAACCTGCTTGGGTATGC
	AGCAGCCTGCTCAGTCACAGCAGGTCACCATCCAAGTCCAAGAGCCTGTTGACATGCTCAGCAACAT
	GCCAGGCACAGCTGCAGGCTCCAGTGGGCGCGGCATCTCCATCAGCCCCAGTGCTGGTCAGATGCAG
	ATGCAGCACCGTACCAACCTGATGGCCACCCTCAGCTATGGGCACCGTCCCTTGTCCAAGCAGCTGA
	GTGCTGACAGTGCAGAGGCTCACAGCTTGAACGTGAATCGGTTCTCCCCTGCTAACTACGACCAGGC
	GCATTTACACCCCCATCTGTTTTCCGACCAGTCCCGGGGTTCCCCCAGCAGCTACAGCCCTTCAACA
	GGAGTGGGGTTCTCTCCAACCCAAGCCCTGAAAGTCCCTCCACTTGACCAATTCCCCACCTTCCCTC
	CCAGTGCACATCAGCAGCCGCCACACTATACCACGTCGGCACTACAGCAGGCCCTGCTGTCTCCCAC
	GCCGCCAGACTATACAAGACACCAGCAGGTACCCCACATCCTTCAAGGACTGCTTTCTCCCCGGCAT
	TCGCTCACCGGCCACTCGGACATCCGGCTGCCCCCAACAGAGTTTGCACAGCTCATTAAAAGGCAGC
	AGCAACAACGGCAGCAGCAGCAGCAACAGCAGCAACAGCAAGAATACCAGGAACTGTTCACGCACAT
	GAACCAAGGGGATGCCGGGAGTCTGGCTCCCAGCCTTGGGGGACAGAGCATGACAGAGCGCCAGGCT
	TTATCTTATCAAAATGCTGACTCTTATCACCATCACACCAGCCCCCAGCATCTGCTACAAATCAGGG
	CACAAGAATGTGTCTCACAGGCTTCCTCACCCACCCCGCCCCACGGGTATGCTCACCAGCCGGCACT
	GATGCATTCAGAGAGCATGGAGGAGGACTGCTCGTGTGAGGGGGCCAAGGATCGCTTCCAAGACAGT
	AAGAGTTCAAGTACATTGACCAAAGGTTGCCATGACAGCCCTCTGCTCTTGAGTACCGGTGGACCTG
	GGGACCCTGAATCTTTGCTAGGAACTGTGAGTCATGCCCAAGAATTGGGGATACATCCCTATGGTCA
	TCAGCCAACTGCTGCATTCAGTAAAAATAAGGTGCCCAGCAGAGAGCCTGTCATAGGGAACTGCATG
	GATAGAAGTTCTCCAGGACAAGCAGTGGAGCTGCCGGATCACAATGGGCTCGGGTACCCAGCACGCC
	CCTCCGTCCATGAGCACCACAGGCCCCGGGCCCTCCAGAGACACCACACGATCCAGAACAGCGACGA
	TGCTTATGTACAGCTGGATAACTTGCCAGGAATGAGTCTCGTGGCTGGGAAAGCACTTAGCTCTGCC
	CGGATGTCGGATGCAGTTCTCAGTCAGTCTTCGCTCATGGGCAGCCAGCAGTTTCAGGATGGGGAAA
	ATGAGGAATGTGGGGCAAGCCTGGGAGGTCATGAGCACCCAGACCTGAGTGATGGCAGCCAGCATTT
	AAACTCCTCTTGCTATCCATCTACGTGTATTACAGACATTCTGCTCAGCTACAAGCACCCCGAAGTC
	TCCTTCAGCATGGAGCAGGCAGGCGTGTAACAAGAAACAGAGAGAGAGCAAGAGGTCCCGAGTCCCC
	TCCTAGTCTTTCATCCTGAATTTGCACACAGGAAAGCGTGTGCCCGGCATGGCCATCCTGATGTTGC
	TGCCGGGATCCCCATGCACCTTGTCCTTCTCCACTGATACTGGCAGCTCGGCTCCTGCACCCAAGAT
	ACCTTGAGTGGAATTCTGCAGTGCAAGAGCCCTTCGTGGGAGCTGTCCCATGTTTCCATGGTCCCCA
	GTCTCCCCTCCACTTGGTGGGGTCACCAACTACTCACCACAAGGGGGCTTACCAACAAAGCCCTAAA
	AAGCTGTTGACTTATCTGCGCTTGTTCCAACTCTTATGCCCCCAACCTGCCCTACCACCACCACGCC
	CTCAGCCTGATGTGTTTACATGGTACTGTATGTATGGGAGAGCAGACTGCACCCTCCAGCAACAACA
	AATGAAAGCCAGTGAGCCTACTAACCGTGCCATCTTGCAAACTACACTTTAAAAAAAACTCATTGCT
	TTGTATTGTAGTAACCAATATGTGCAGTATACGTTGAATGTATATGAACATACTTTCCTATTTCTGT
	TCTTTGAAAATGTCAGAAATATTTTTTTCTTTCTCATTTTATGTTGAACTAAAAAGGATTAAAAAAA
	AAATCTCC
	ORF Start: ATG at 420		ORF Stop: TAA at 4383
	SEQ ID NO: 162	1321 aa	MW at 144850.0kD
NOV37d,	MAAAAASGAGGAAGAGTGGAGPAGRLLPPPAPGSPAAPAAVSPAAGQPRPPAPASRGPMPARIGYYE
CG89709-04
Protein Sequence	IDRTIGKGNFAXTVKRATHLVTKAKVAIKHDKTQLDEENLKKIFREVQIMKMLCHPHIIRLYQVMET
	ERMIYLVTEYASGGEIFDHLVAHGRMAEKEARRKFKQIVTAVYFCHCRNTVHRDLKAENLLLDANLN
	IKIADFGFSNLFTPGQLLKTWCGSPPYAAPELFEGKEYDGPKVDIWSLCVVLYVLVCGALPFDGSTL
	QNLRARVLSGKFRIPFFMSTECEHLIRHMLVLDPNKRLSMEQICKHKWMKLGDADPNFDRLIAECQQ
	LKEERQVDPLNEDVLLAMEDMGLDKEQTLQSLRSDAYDHYSAIYSLLCDRHKRHKTLRLGALPSMPR
	ALAFQAPVNIQAEQAGTAMNISVPQVQLINPENQIVEPDGTLNLDSDEGEEPSPEALVRYLSMRRHT
	VGVADPRTEVMEDLQKLLPGFPGVNPQAPFLQVAPNVNFMHNLLPMQNLQPTGQLEYKEQSLLQPPT
	LQLLNGMGPLGRRASDGGANIQLHAQQLLKRPRGPSPLVTMTPAVPAVTPVDEESSDGEPDQEAVQS
	STYKDSNTLHLFTERFSPVRRFSDGAASIQAFKAHLEKMGNNSSIKQLQQECEQLQKMYGGQIDERT
	LEKTQQQHMLYQQEQHHQILQQQIQDSICPPQPSPPLQAACENQPALLTHQLQRLRIQPSSPPPNHP
	NNHLFRQPSNSPPPMSSAMIQPHGAASSSQFQGLPSRSAIFQQQPENCSSPPNVALTCLGMQQPAQS
	QQVTIQVQEPVDMLSNMPGTAAGSSGRGISISPSAGQMQMQHRTNLMATLSYGHRPLSKQLSADSAE
	AHSLNVNRFSPANYDQAHLHPHLFSDQSRGSPSSYSPSTGVGBSPTQALKVPPLDQFPTFPPSAHQQ
	PPHYTTSALQQALLSPTPPDYTRHQQVPHILQGLLSPRHSLTGHSDIRLPPTEFAQLIKRQQQQRQQ
	QQQQQQQQEYQELFRHMNQGDAGSLAPSLGGQSMTERQALSYQNADSYHHHTSPQHLLQIRAQECVS
	QASSPTPPHGYAHQPALMHSESMEEDCSCEGAKDGFQDSKSSSTLTKGCHDSPLLLSTGGPGDPESL
	LGTVSHAQELGIHPYGHQPTAAFSKNKVPSREPVIGNCMDRSSPGQAVELPDHNCLGYPARFSVHEH
	HRPRALQRHHTIQNSDDAYVQLDNLPGMSLVAGKALSSARMSDAVLSQSSLMCSQQFQDGENEECGA
	SLGGHEHPDLSDGSQHLNSSCYPSTCITDILLSYXHPEVSFSMEQAGV
	SEQ ID NO: 163	3807 bp
NOV37e,	ATGGCGGCGGCGGCGGCGAGCGGAGCTGGCGGGGCTGCCGGGGCCGGGACTGGGGGAGCCGGGCCCG
CG89709-01
DNA Sequence	CGGGCCGCCTGCTGCCTCCGCCCGCGCCGGGGTCCCCAGCCGCCCCCGCTGCCGTGTCCCCTGCGGC
	CGGCCAGCCGCGTCCCCCAGCCCCGGCCTCCCGCGGACCCATGCCCGCCCCTATCGGCTACTACGAG
	ATCGACCGCACCATCGGCAAGGGCAACTTCGCGGTGGTCAAGCGGGCCACGCACCTCGTCACCAAGG
	CCAAGGTTGCTATCAAGATCATAGATAAGACCCAGCTGGATGAAQAAAACTTGAAGAAGATTTTCCG
	GGAAGTTCAAATTATGAAGATGCTTTGCCACCCCCATATCATCAGGCTCTACCAGGTTATGGAGACA
	GAACGGATGATTTATCTGGTCACAGAATATGCTAGTGGAGGCGAAATATTTCACCACCTGGTGGCCC
	ATGGTAGAATGGCAGAAAAGGAGGCACGTCGGAAGTTCAAACAGATCGTCACAGCTGTCTATTTTTG
	TCACTGTCCGAACATTGTTCATCGTGATTTAAAAGCTGAAAATTTACTTCTGGATGCCAATCTGAAT
	ATCAAAATAGCAGATTTTGGTTTCAGTAACCTCTTCACTCCTGGGCAGCTACTGAAGACCTGGTGTG
	GCAGCCCTCCCTATGCTGCACCTGAACTCTTTGAAGGAAAAGAATATGATGGGCCCAAAGTGGACAT
	CTGGAGCCTTGGAGTTGTCCTCTACGTGCTTGTGTGCGGTGCCCTGCCATTTCATGGAAGCACACTG
	CAGAATCTGCGGGCCCGCGTGCTGAGTGGAAAGTTCCGCATCCCATTTTTTATGTCCACAGAATGTG
	AGCATTTGATCCGCCATATGTTGGTGTTAGATCCCAATAAGCGCCTCTCCATGGAGCAGATCTGCAA
	GCACAAGTGGATGAGCTAGGGGACGCCGATCCCAACTTTGACAGGTTAATTAGCTGAATGCCAACAA
	CTAAAGGAAGAAAGACAGGTGGACCCCCTGAATGAGGATGTCCTCTTGGCCATGGAGGACATGGGAC
	TGGACAAAGAACAGACACTGCAGGCGGAGCAGGCAGGTACTGCTATGAACATCAGCGTTCCCCAGGT
	GCAGCTGATCAACCCAGAGAACCAAATTGTCGAGCCGGATGGGACACTGAATTTGGACAGTGATGAG
	GGTGAAGAGCCTTCCCCTGAAGCATTGGTGCGCTATTTGTCAATGAGGAGGCACACAGTGGGTGTGG
	CTGACCCACGCACGGAAGTTATGGAAGATCTGCAGAAGCTCCTACCTGGCTTTCCTGGAGTCAACCC
	CCAGGCTCCATTCCTGCAGGTGGCCCCTAATGTGAACTTCATGCACAACCTGTTGCCTATGCAAAAC
	TTGCAACCAACCGGGCAACTTGAGTACAAGGAGCAGTCTCTCCTACAGCCGCCCACGCTACAGCTGT
	TGAATCCAATGGCCCCCCTTGGCCGGAGGGCATCAGATGGAGGAGCCAACATCCAACTCCATGCCCA
	GCAGCTGCTGAAGCGCCCACGGGGACCCTCTCCGCTTGTCACCATGACACCAGCAGTGCCAGCAGTT
	ACCCCTGTGGACGAGGAGAGCTCAGACGGGGACCCAGACCACGAAGCTGTGCAGAGCTCTACCTACA
	AGGACTCCAACACTCTGCACCTCCCTACGGAGCGTTTCTCCCCTGTGCGCCGGTTCTCAGATGGGGC
	TGCGAGCATCCAGGCCTTCAAAGCTCACCTGGAAAAAATGCGCAACAACAGCAGCATCAAACAGCTG
	CAGCAGGAGTGTGAGCAGCTGCAGAAGATGTACGGGGGGCAGATTGATGAAAGAACCCTGGAGAAGA
	CCCAGCAGCAGCATATGTTATACCAGCAGGAGCAGCACCATCAAATTCTCCAGCAACAAATTCAAGA
	CTCTATCTGTCCTCCTCAGCCATCTCCACCTCTTCAGGCTGCATGTGAAAATCAGCCAGCCCTCCTT
	ACCCATCAGCTCCAGAGGTTAAGGATTCAGCCTTCAAGCCCACCCCCCAACCACCCCAACAACCATc
	TCTTCAGOCAGCCCAGTAATAGTCCTCCCCCCATGAGCAGTGCCATGATCCAGCCTCACGGGGCTGC
	ATCTTCTTCCCAGTTTCAAGGCTTACCTTCCCCCAGTGCTTCTTTCAGCAGCACCTGAGTAGTCTGT
	TCCTCTCCTCCCAACGTGGCACTAACCTGCTTGGGTATGCAGCAGCCTGCTCAGTCACAGCAGGTCA
	CCATCCAAGTCCAAGAGCCTGTTGACATGCTCAGCAACATGCCAGCCACAGCTGCAGGCTCCAGTGG
	GCGCGGCATCTCCATCAGCCCCAGTGCTGGTCAGATGCAGATGCAGCACCGTACCAACCTGATGGCC
	ACCCTCAGCTATGGGCACCGTCCCTTGTCCAAGCAGCTGAGTGCTGACTAAGTCCAGACTCACAGTG
	CACATCAGCAGCCGCCACACTATACCACGTCGGCACTACAGCAGGCCCTGCTGTCTCCCACGCCGCC
	AGACTATACAAGACACCAGCAGGTACCCCACATCCTTCAAGGACTCCTTTCTCCCCGGCATTCGCTC
	ACCGGCCACTCGGACATCCGGCTGCCCCCAACAGAGTTTGCACAGCTCATTAACGCAGCAGCAAGAC
	AACGGCAGCAGCAGCAGCAACAGCAGCAACAGCAAGAATACCAGGAACTGTTCAGGCACATGAACCA
	AGGGCATGCGGGGAGTCTGGCTCCCAGCCTTGGGGGACAGAGCATGACAGAGCGCCAGGCTTTATCT
	TATCAAAATGCTGACTCTTATCACCACACGATCCAGAACAGCGACGATGCTTATGTACAGCTAAATA
	ACTTGCCAGGAATGAGTCTCGTGGCTGGGAAAGCACTTAGCTCTGCCCGGATGTCGGATGCAGTTCT
	CAGTCAGTCTTCGCTCATGGGCAGCCAGCAGTTTCAGGATGGGGAAAATGAGGAATGTGGGGCAAGC
	CTGGGAGGTCATGAGCACCCAGACCTGAGTGATGGCAGCCAGCATTTAAACTCCTCTTGCTATCCAT
	CTACGTGTATTACAGACATTCTGCTCAGCTACAAGCACCCCGAAGTCTCCTTCAGCATAAAGCAGGC
	AGGCGTGTAACAGAAACAGAGAGACAGCAIXGAGGTCCCGAGTCCCCTCCTAGTCTTTCATCCTGGG
	TTTGCACAGAGGAAAGCGGGTGCCCGGCATGGCCATCCTGATGTTGCTGGCGGGATCCCCATGCACC
	TTGTCCTTCTCCACTGATACTGCCAGCTCGGCTCCTGGACCCAAGATCCCTTGAGTGGAGTTCTGCA
	GTGCAAGAGCCCTTCGTGGGAGCTGTCCCATGTTTCCATGGTCCCCAGTCTCCCCTCCACTTGGTGC
	GGTCACCAACTACTCACCAGAACGGGGCTTACCAAGAAAGCCCTAAAAAGCTGTTGACTTATCTGCG
	CTTGTTCCAACTCTTATGCCCCCAACCTGCCCTACCACCACCACGCGCTCAGCCTGATGTGTTTACA
	TGGTACTGTATGTATGGGAGAGCAGACTGCACCCTCCAGCAACAACAGATGAAGCCAGTGAGCCTAA
	CTAACCGTGCCATCTTGCAAACTACACTTTAAAAAAAACTCATTGCTTTGTATTGTAGTAACCAATA
	TGTGCAGTATACGTTGAATGTATATGAACATACTTTCCTATTTCTGTTCTTTGAAAATGTCAGAAAT
	ATTTTTTTCTTTCTCATTTTATGTTGAACTAAAAGCATTAAAAAAAAAAAATCTCC
	ORF Start: ATG at 1		ORF Stop: TAA at 3157
	SEQ ID NO: 164	1052 aa	MW at 115587.7kD
NOV37e,	MAAAASGAGGAAGAGTGGAGPAGRLLPPPAPGSPAAPAAVSPAAGQRPRPPAPASRGPMPARIGYYE
CG89709-01
Protein Sequence	IDRTIGKGNFAVVKRATHLVTKAKVAIKIIDKTQLDEENLKKIFREVQIMKMLCHPHIIRLYQVMET
	ERMIYLVTEYASGGEIFDHLVAHGRMAEKEARRKFKQIVTAVYFCHCRNIVHRDLKAENLLLDANLN
	IKIADFGFSNLFTPGQLLKTWCGSPPYAAPELFEGKEYDGPKVDIWSLGVVLYVLVCGALPFDGSTL
	QNLRARVLSGKFRIPFFMSTECEHLIRHMLVLDPNKRLSMEQICKHKWMKLGDADPNFDRLIAECQQ
	LKEERQVDPLNEDVLLAMEDMGLDKEQTLQAEQAGTAMNISVPQVQLINPENQIVEPDGTLNLDSDE
	GEEPSPEALVRYLSMRRHTVGVADFRTEVMEDLQKLLPGFPGVNPQAPFLQVAPNVNFNTDLLPMQN
	LQPTGQLEYKEQSLLQPFTLQLLNGMGPLGRRASDGGANIQLHAQQLLKRPRGPSPLVTMTTAVPAV
	TPVDEESSDGEPDQEAVQSSTYKDSNTLHLPTERFSPVRRFSDGAASIQAFKAHLEKMGNNSSIKQL
	QQECEQLQKMYGGQIDERTLEKTQQQHMLYQQEQHHQILQQQTQDSICPPQPSPPLQAACENQPALL
	THQLQRLRIQPSSPPPNHPNNHLFRQPSNSPPPMSSAMIQPHGAASSSQFQGLPSRSAIFQQQPENC
	SSPPNVALTCLGMQQPAQSQQVTIQVQEPVDMLSNMPGTAAGSSGRGISISPSAGQMQMQHRTNLMA
	TLSYGHRPLSKQLSADSAEAHSAHQQPPHYTTSALQQALLSPTPPDYTRHQQVPHILQGLLSPRHSL
	TGHSDIRLPPTEFAQLIKRQQQQRQQQQQQQQQQEYQELFRHMNQGDAGSLAPSLGGQSMTERQALS
	YQNADSYHHTIQNSDDAYVQLDNLPGMSLVAGKALSSARMSDAVLSQSSLMGSQQFQDGENEECGAS
	LGGHEHPDLSDGSQHLNSSCYPSTCITDILLSYKHPEVSFSMEQAGV

[0550] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 37B.

TABLE 37B
Comparison of NOV37a against NOV37b through NOV37e.
			Identities/
			Similarities for
	Protein	NOV37a Residues/	the Matched
	Sequence	Match Residues	Region
	NOV37b	62 . . . 1052	886/1051 (84%)
		62 . . . 1112	887/1051 (84%)
	NOV37c	62 . . . 947	781/946 (82%)
		62 . . . 1007	782/946 (82%)
	NOV37d	62 . . . 947	781/994 (78%)
		62 . . . 1055	782/994 (78%)
	NOV37e	62 . . . 1052	892/991 (90%)
		62 . . . 1052	892/991 (90%)

[0551] Further analysis of the NOV37a protein yielded the following properties shown in Table 37C.

TABLE 37C
Protein Sequence Properties NOV37a
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   No Known Signal Sequence Predicted
analysis:

[0552] 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/
			Similarities for
Geneseq	Protein/Organism/Length	NOV37a Residues/	the Matched	Expect
Identifier	[Patent #, Date]	Match Residues	Region	Value
AAB43286	Human ORFX ORF3050	11 . . . 1052	1022/1102 (92%)	0.0
	polypeptide sequence SEQ	1 . . . 1102	1026/1102 (92%)
	ID NO: 6100 - Homo
	sapiens, 1102 aa.
	[WO200058473-A2,
	05 OCT. 2000]
AAE21712	Human PKIN-7 protein -	1 . . . 947	940/1103 (85%)	0.0
	Homo sapiens, 1369 aa.	1 . . . 1103	941/1103 (85%)
	[WO200218557-A2,
	07 MAR. 2002]
AAB65626	Novel protein kinase, SEQ	59 . . . 947	821/996 (82%)	0.0
	ID NO: 152 - Homo sapiens,	1 . . . 985	831/996 (83%)
	1251 aa.
	[WO200073469-A2,
	07 DEC. 2000]
ABG08443	Novel human diagnostic	204 . . . 830	597/776 (76%)	0.0
	protein #8434 - Homo	43 . . . 818	603/776 (76%)
	sapiens, 1265 aa.
	[WO200175067-A2,
	11 OCT. 2001]
AAB65631	Novel protein kinase, SEQ	51 . . . 368	202/318 (63%)	e−115
	ID NO: 158 - Homo sapiens,	7 . . . 319	251/318 (78%)
	926 aa. [WO200073469-A2,
	07 DEC. 2000]

[0553] 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
			Identities/
Protein			Similarities for
Accession		NOV37a Residues/	the Matched	Expect
Number	Protein/Organism/Length	Match Residues	Portion	Value
Q9Y2K2	KIAA0999 protein - Homo	6 . . . 947	935/1050 (89%)	0.0
	sapiens (Human), 1371 aa	56 . . . 1105	937/1050 (89%)
	(fragment).
Q9CYD5	5730525O22Rik protein -	117 . . . 554	425/486 (87%)	0.0
	Mus musculus (Mouse), 487	1 . . . 486	433/486 (88%)
	aa.
BAA34501	KIAA0781 protein - Homo	22 . . . 368	210/347 (60%)	e−117
	sapiens (Human), 950 aa	2 . . . 343	261/347 (74%)
	(fragment).
BAB91442	KIAA0781 protein - Homo	51 . . . 368	203/318 (63%)	e−116
	sapiens (Human), 346 aa	5 . . . 317	252/318 (78%)
	(fragment).
Q9H0K1	Hypothetical 103.9 kDa	51 . . . 368	203/318 (63%)	e−116
	protein (KIAA0781 protein) -	7 . . . 319	252/318 (78%)
	Homo sapiens (Human),
	926 aa.

[0554] PFam analysis predicts that the NOV37a protein contains the domains shown in the Table 37F.

TABLE 37F
Domain Analysis of NOV37a
			Identities/
		NOV37a	Similarities for
	Pfam	Match	the Matched	Expect
	Domain	Region	Region	Value
	pkinase	66 . . . 317	106/291 (36%)	4.7e−97
			219/291 (75%)

Example 38

[0555] 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: 165	2927 bp
NOV38a,	CCGGGTGGGCTCCAGGCGGCCGGTCCCCGGCCTCCCCCCATGGCCACCGCCCCCTCTTATCCCGCCG
CG90879-01
DNA Sequence	GGCTCCCTGGCTCTCCCGGGCCGGGGTCTCCTCCGCCCCCCGGCGGCCTAGAGCTGCAGTCGCCGCC
	ACCGCTACTGCCCCAGATCCCGGCCCCGGGTTCCGGGGTCTCCTTTCACATCCAGATCGGGCTGACC
	CGCGAGTTCGTGCTGTTGCCCGCCGCCTCCGAGCTGGCTCATGTGCGCAGCTGGCCTGGTTCCATCG
	TGGACCAGAAGTTCCCTGAGTGTGGCTTCTACGGCCTTTACCACAAGATCCTGCTTTTACAGCATGA
	CCCCACCTCGGCCAACCTCCTGCAGCTGGTGCGCTCGTCCGGAGACATCCACGAGGGCGTACCTGTG
	GAGGTGGTGCTGTCGGCCTCGGCCACCTTCGAGGACTTCCAGATCCGCCCGCACGCCCTCACGGTGC
	ACTCCTATCGGGCGCCTGCCTTCTGTGATCACTGCGGGGAGATGCTCTTCGGCCTAGTGCGCCAGGG
	CCTCAAGTGCGATGGCTGCGGGCTGAACTACCACAAGCGCTGTGCCTTCAGCATCCCCAACAACTGT
	AGTGGGGCCCGCAAACGGCGCCTGTCATCCACGTCTCTGGCCAGTGGCCACTCGGTGCGCCTCGGCA
	CCTCCGAGTCCCTGCCCTGCACGGCTGAAGAGCTCAGCCGTAGCACCACCGATCTCCTGCCTCGCCG
	TCCCCCGTCATCCTCTTCCTCCTCTTCTGCCTCATCGTATACGGGCCGCCCCATTGAGCTGGACTAG
	ATGCTGCTCTCCAAGGTCAAGGTGCCGCACACCTTCCTCATCCACAGCTATACACGGCCCACCGTTT
	GCCAGGCTTGCAAGAAACTCCTCAAGGGCCTCTTCCGGCAGGGCCTGCAATGCAAAGACTGCAAGTT
	TAACTGTCACAAACGCTGCGCCACCCGCGTCCCTAATGACTGCCTGGGGGAGGCCCTTATCAATGGA
	GACCCCTCTGATGCCTCCGTCCCCACAGATGTGCCGATGGAGGAGGCCACCGATTTCAGCGAGGCTG
	ACAAGAGCGCCCTCATGGATGAGTCAGAGGACTCCGGTGTCATCCCTGGCTCCCACTCAGAGAATGC
	GCTCCACGCCAGTCAGGAGGAGGAAGGCGAGGGAGGCTAGGCCCAGAGCTCCCTGGGGTACATCCCC
	CTAATGAGGGTGGTGCAATCGGTGCGACACACGACGCGGAAATCCAGCACCACGCTGCGGGAGGGTT
	GGGTGGTTCATTACAGCAACAAGGACACGCTGAGAAAGCGGCACTATTGGCGCCTGGACTGCAAGTG
	TATCACGCTCTTCCAGAACAACACCACCAACAGATACTATAAGGAATTCCGCTGTCAGATTCATCTC
	ACGGTGCAGTCCGCCCAGAACTTCAGCCTTGTGCCGCCGGGCACCAACCCACACTGCTTTGAGATCG
	TCACTGCCAATGCCACCTACTTCGTGGGCGAGATGCCTGGCGGGACTCCGGGTGGGCCAAGTGGGCA
	GGGGGCTGAGGCCGCCCGGGGCTGGGAGACAGCCATCCGCCAGGCCCTGATGCCCGTCATCCTTCAG
	GACGCACCCAGCGCCCCAGGCCACGCGCCCCACAGACAAGCTTCTCTGAGCATCTCTGTGTCCGTCA
	GTCAGATCCAAGAGAATGTGGACATTGCCACTGTCTACCAGATCTTCCCTGACGACGTGCTGGGCTC
	AGGGCAGTTTGGAGTGGTCTATGGAGGGAAACACCGGAAGACAGGCCGGGACGTGGCAGTTAAGGTC
	ATTGACAAACTGCGCTTCCCTACCAAGCAGGAGAGCCAGCTCCGGAATGAAGTGGCCATTCTGCAGA
	GCCTGCGGCATCCCGGGATCGTGAACCTGGAGTGCATGTTCGAGACGCCTGAGTGACTGTTTGTGGT
	GATGGAGAAGCTGCATGGGGACATGTTGGAGATGATCCTGTCCAGTGAGTAGGGCCGGCTGCCTGAG
	CGCCTCACCAAGTTCCTCATCACCCAGATCCTGGTGGCTTTCAGACACCTTCACTTCTAGTACATTG
	TCCACTGTGACTTGAAACCAGAAAACGTGTTGCTGGCATCAGCAGACCCATTTCCTCAGGTGAAGCT
	GTGTGACTTTGGCTTTGCTCGCATCATCGGCGAGAAGTCGTTCCGCCGCTCAGTGGTGGGCACGCCG
	GCCTACCTGGCACCCGAGCTGCTGCTCAACCAGGGCTACTACCGCTCGCTGGACATGTGGTCAGTGG
	GCGTGATCATGTACGTCAGCCTCAGCGGCACCTTCCCTTTCAACGAGGATGAGGACATCAATGACCA
	GATCCAGAACGCCGCCTTCATGTACCCCGCCAGCCCCTGGAGCCACATCTCAGCTTAAGCCATTGAC
	CTCATCAACAACCTGCTGCAGGTGAAGATGCGCAAACGCTACAGCGTGGACAAATCTCTCAGCCACC
	CCTGGTTACAGGAGTACCAGACGTGGCTGGACCTCCGAOAGCTGGAGGGGAAGATGGGAGAGCGATA
	CATCACGCATGAGAGTGACGACGCGCGCTGCGAGCAGTTTGCAGCAGAGCATCCGCTGCCTGGGTCT
	GGGCTGCCCACGGACAGGGATCTCGGTGGGGCCTGTCCACCACAGGACCACGACATGCAGGGGCTTA
	CGGAGCGCATCAGTGTTCTCTGAGGTCCTGTGCCCTCGTCCAGCTGCTGCCCTCCACAGCGGTTCTT
	CACAGGATCCCAGCAATGAACTGTTCTAGGGAAAGTOGCTTCCTGCCCAAACTGGATTAGACACGTG
	GGGAGTGGGGTGGGGGGAGCTATTTCCAAGGCCCCTCCCTGTTTCCCCAGCAATTAAAACGGACTCA
	TCTCTGGCCCCATGGCCTTGATCTCAAAAAAAAAAAAAAAAAAAAA
	ORF Start: ATG at 40		ORF Stop: TGA at 2701
	SEQ ID NO: 166	887 aa	MW at 97590.9kD
NOV38a,	MATAPSYPAGLPGSPGPGSPPPGGLELQSPPPLLPQIPAPGSGVSFHIQIGLTREFVLRLPAASELA
CG90879-01
Protein Sequence	HVKQLACSIVDQKFPECGFYGLYDKILLFKHDPTSANLLQLVRSSGDIQEGDLVEVVLSASATFEDF
	QTRPHALTVHSYRAPAFCDHCGEMLFGLVRQGLKCDGCGLNYHKRCAYSIPNNCSGARKRRLSSTSL
	ASGHSVRLGTSESLPCTAEELSRSTTELLPRRPPSSSSSSSASSYTGRPIELDKMLLSKVKVFHTFL
	IHSYTRPTVCQACKKLLKGLFRQGLQCKDCKFNCHKRCATRVPNDCLGKRAINGDPSDASVPTDVPM
	EEATDFSEADKSALMDESEDSGVIPGSHSENALHASEEEEGEGGKAQSSLGYIPLMRVVQSVRHTTR
	RSSTTLREGWVVHYSNKDTLRKRHYWRLDCKCITLFQNNTTNRYYKEIPLSEILTVESAQNFSLVPP
	GTNPHCFEIVTANATYFVGEMPGGTPGGPSCQGAEAARGWETAIRQALMPVILQDAPSAPGKGPHRQ
	ASLSISVSNSQIQENVDIATVYQIFPDEVLGSGQFGVVYGGKHRKTGRDVATKVIDKLRFPTKQESQ
	LRNEVAILQSLRHPGIVNLECMFETPEKVFVVMEKLHGDMLEMILSSEKGRLPERLTKULITQILVA
	LRHLHFKNIVHCDLKPENVLLASALPFPQVKLCDFGFKHIGEKSFRRSVVGTPAYLAPEJVLLNQGY
	NRSLDMWSVGVINYVSLSGTFPFNEDEDINDQTQNAAFNYPASPWSHISAGAIDLIARLLQVKMRKR
	YSVDKSLSHPWLQEYQTWLDLRELEGKMGERYITHESDDARWEQFKGEHPLPGSGLPTDRDLGGACP
	PQDHDMQGLAERISVL

[0556] Further analysis of the NOV38a protein yielded the following properties shown in Table 38B.

TABLE 38B
Protein Sequence Properties NOV38a
PSort     0.9600 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:

[0557] 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
			Identities/
			Similarities for
Geneseq	Protein/Organism/Length	NOV38a Residues/	the Matched	Expect
Identifier	[Patent #, Date]	Match Residues	Region	Value
AAE22768	Human protein kinase D2	1 . . . 887	878/887 (98%)	0.0
	(PKD2) - Homo sapiens, 878	1 . . . 878	878/887 (98%)
	aa. [WO200224947-A2,
	28 MAR. 2002]
AAE22719	Human kinase protein -	1 . . . 887	878/887 (98%)	0.0
	Homo sapiens, 878 aa.	1 . . . 878	878/887 (98%)
	[WO200222795-A2,
	21 MAR. 2002]
AAE11771	Human kinase (PKIN)-5	1 . . . 887	878/887 (98%)	0.0
	protein - Homo sapiens, 878	1 . . . 878	878/887 (98%)
	aa. [WO200181555-A2,
	01 NOV. 2001]
AAB65604	Novel protein kinase, SEQ	5 . . . 887	872/884 (98%)	0.0
	ID NO: 130 - Homo sapiens,	104 . . . 978	872/884 (98%)
	978 aa. [WO200073469-A2,
	07 DEC. 2000]
AAU17318	Novel signal transduction	58 . . . 887	820/830 (98%)	0.0
	pathway protein, Seq ID 883 -	1 . . . 821	820/830 (98%)
	Homo sapiens, 821 aa.
	[WO200154733-A1,
	02 AUG. 2001]

[0558] 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
			Identities/
Protein			Similarities for
Accession		NOV38a Residues/	the Matched	Expect
Number	Protein/Organism/Length	Match Residues	Portion	Value
Q9BZL6	Protein kinase C, D2 type (EC	1 . . . 887	878/887 (98%)	0.0
	2.7.1.-) (nPKC-D2) (Protein	1 . . . 878	878/887 (98%)
	kinase D2) (Protein
	HSPC187) - Homo sapiens
	(Human), 878 aa.
Q15139	Protein kinase C, mu type	2 . . .887	626/918 (68%)	0.0
	(EC 2.7.1.-) (nPKC-mu)	19 . . . 912	719/918 (78%)
	(Protein kinase D) -
	Homo sapiens (Human), 912 aa.
Q62101	Protein kinase C, mu type	2 . . . 887	621/918 (67%)	0.0
	(EC 2.7.1.-) (nPKC-mu)	19 . . . 918	719/918 (77%)
	(Protein kinase D) - Mus
	musculus (Mouse), 918 aa.
O94806	Protein kinase C, nu type (EC	8 . . . 855	573/861 (66%)	0.0
	2.7.1.-) (nPKC-nu) (Protein	20 . . . 871	665/861 (76%)
	kinase EPK2) - Homo sapiens
	(Human), 890 aa.
T08777	probable protein kinase C (EC	346 . . . 887	542/542 (100%)	0.0
	2.7.1.-) mu - human, 542 aa	1 . . . 542	542/542 (100%)
	(fragment).

[0559] PFam analysis predicts that the NOV38a protein contains the domains shown in the Table 38E.

TABLE 38E
Domain Analysis of NOV38a
			Identities/
		NOV38a	Similarities for
	Pfam	Match	the Matched	Expect
	Domain	Region	Region	Value
	DAG_PE-bind	139 . . . 188	28/51 (55%)	1.4e−16
			41/51 (80%)
	DAG_PE-bind	265 . . . 314	23/51 (45%)	3.3e−20
			45/51 (88%)
	PH	407 . . . 487	19/81 (23%)	2.2e−08
			58/81 (72%)
	pkinase	560 . . . 816	96/297 (32%)	3.4e−75
			200/297 (67%)

Example 39

[0560] 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: 167	2292 bp
NOV39a,	ATGCATACAGGAGGAGAGACTTCAGCATGCAAACCTTCATCTGTCCGGCTTGCACCGTCGTTCTCAT
CG96334-01
DNA Sequence	TCCATGCTGCTGGCCTTCAGATGGCTGCACAGATGCCCCACTCACACCAGTACAGTGACCGTCGCCA
	GCCGAGCATAAGTGACCAGCAGGTGTCTGCCTTACCATATTCTGACCAGATTCAGCAACCTCTAACT
	AACCAGGTGATGCCTGACATTGTCATGTTACAGAGGCGGATGCCCCAAACCTTCCGTGATCCAGCAA
	CTGCTCCTCTGAGAAAACTCTCTGTGGACTTGATCAAAACATACAAGCATATTAATGAGGTTTACTA
	TGCAAAAAAGAAGCGAAGACACCAACAGGGCCGGGGGGACGATTCCAGTCATAAGAAGGAGCGGAAG
	GTTTACAATGATGGTTACGATGATGATAACTATGATTATATTGTAAAAAACGGCOAAAAGTGGATGG
	ATCGGTATGAAATCGACTCCTTAATAGGCAAAGGTTCATTTGGACAGGTTGTGAAAGCTTATGACAG
	AGTGGAGCAAGAATGGGTCCCCATTAAAATCATCAAGAACAAGAAAGCGTTTCTGAATCAAGCCCAG
	ATAGAAGTGCGGCTGCTTGAGCTCATGAACAAACACGACACTGAAATGAAGTACTACATAGTGCATT
	TGAAACGCCACTTTATGTTTCGAAACCATCTCTGTTTAGTGTTTGAAATGCTGTCCTATAATCTCTA
	TGATTTGTTGAGAAACACCAACTTCCGAOCGGTCTCTTTGAACCTAACACGAAAGTTTGCGCAACAG
	ATGTGCACAGCATTGCTTTTTCTTGCGACTCCAGAACTTAGTATCATTCACTGTGACTTAAAGCCTG
	AGAACATCCTTCTTTGTAACCCCAAACGCAGTGCAATCAAGATAGTTGACTTTGGCAGTTCTTGTCA
	GTTGGGGCAGAGGATATACCAGTATATTCAGAGTCGCTTTTATCGGTCTCCAGAGGTGCTACTGGGA
	ATGCCTTATGACCTTGCCATTOATATGTGGTCCCTCGGGTGTATTTTGGTTGAAATGCACACTGGAG
	AACCTCTGTTCAGTGGTGCCAATGAGGTAGATCAGATGAATAAAATACTGGAAGTTCTGGGTATTCC
	ACCTGCTCATATTCTTGACCAAGCACCAAAAGCAAGAAAGTTCTTTGAGAATTTGCCAGATGGCACT
	TGGAACTPAAAGAAGACCAAAGATGGAAAACGGGAGTACAAACCACCAGGAACCCGTAAACTTCATA
	ACATTCTTGGAGTGGAAACAGGAGGACCTGGTGGGCGACGTGCTGGGGAGTCAGGTCATACGGTCGC
	TGACTACTTGAAGTTCAAAGACCTCATTTTAAGGATGCTTGATTATGACCCCAAAACTCGAATTCAA
	CCTTATTATGCTCTGCAGCACAGTTTCTTCAAGAAAACAGCTGATGAAGGTACAAATACAACTAATA
	GTCTATCTACAAGCCCCGCCATGGACCAGTCTCAGTCTTCGCGCACCACCTCCAGTACATCGTCAAG
	CTCAGGTGGCTCATCGGGGACAAGCAACAGTGGGAGAGCCCGGTCGGATCCGACGCACCAGCATCGG
	CACAGTGGTCGGCACTTCACAGCTGCCGTGCAGGCCATGGACTGCGAGACACACAGTCCCCAGGTGC
	GTCAGCAATTTCCTGCTCCTCTTGGTTGGTCAGGCACTGAAGCTCCTACACAGGTCACTGTTGAAAC
	TCATCCTGTTCAAGAAACAACCTTTCATGTAGGCCCTCAACAGAATGCATTGCATCATCACCATGGT
	AACAGTTCCCATCACCATCACCACCACCACCACCATCACCACCACCATGGACAACAAGCCTTGGGTA
	ACCGGACCACGCCAAGCGTCTACAATTCTCCAACGAATAGCTCCTCTACCCAAGATTCTATGGAGGT
	TGGCCACAGTCACCACTCCATGACATCCCTGTCTTCCTCAACGACTTCTTCCTCGACATCTTCCTCC
	TCTACTGGTAACCAAGGCAATCAGCCCTACCAGAATCGCCCAGTGGCTGCTAATACCTTGGACTTTG
	GACAGAATGGAGCTATGGACGTTAATTTGACCGTCTACTCCAATCCCCGCCAAGAGACTGGCATAGC
	TGGACATCCAACATACCAATTTTCTGCTAATACAGGTCCTGCACATTACATGACTGAAGGACATCTG
	ACAATGAGGCAAGGGGCTGATAGAGAAGAGTCCCCCATGACAGGAGTTTGTGTGCAACAGAGTCCTG
	TAGCTAGCTCGTGA
	ORF Start: ATG at 1		ORF Stop: TGA at 2290
	SEQ ID NO: 168	763 aa	MW at 85606.2kD
NOV39a,	MHTGGETSACKPSSVRLAPSFSFHAAGLQMAAQMPHSHQYSDRRQPSISDQQVSALPYSDQIQQPLT
CG96334-01
Protein Sequence	NQVMPDIVMLQRRMPQTFRDPATAPLRKLSVDLIKTYKHINEVYYAXKKRRHQQGRGDDSSHKKERK
	VYNDGYDDDNYDYIVKNGEKWMDRYEIDSLIGKGSFGQVVKAYDRVEQEWVAIKIIKNKKAFLNQAQ
	IEVRLLELMNKHDTEMXYYIVHLKRHFMFRNHLCLVFEMLSYNLYDLLRNTNFRGVSLNLTRKFAQQ
	MCTALLFLATPELSIIHCDLKPENILLCNPKRSAIKIVDFGSSCQLGQRIYQYIQSRTYRSPEVLLG
	MPYDLAIDMWSLGCILVEMHTGEPLFSGANEVDQMNKIVEVLGIPPAHILDQAPKARKFFENLPDGT
	WNLKKTKDGKREYKPPGTRKLHNILGVETGGPGGRRAGESGHTVADYLKFKDLILRMLDYDPKTRIQ
	PYYALQHSFFKKTADEGThTSNSVSTSPAMEQSQSSGTTSSTSSSSGGSSGTSNSGRARSDPTHQHR
	HSGGHFTAAVQAMDCETHSPQVRQQFPAPLGWSGTEAPTQVTVETHPVQETTFHVGPQQNALHHHHG
	NSSHHHHHHHHHHHHHGQQALGNRTRPRVYNSPTNSSSTQDSMEVGHSHHSMTSLSSSTTSSSTSSS
	STGNQGNQPYQNRPVAANTLDFGQNGAMDVNLTVYSNPRQETGIAGHPTYQFSANTGPAHYMTEGHL
	TMRQGADREESPMTGVCVQQSPVASS
	SEQ ID NO: 169	1369 bp
NOV39b,	GACTTGAAAGAAGACGATGCATACAGGAGGAGACACTTCAGCATGCAAACCTTCATCTGTTCGGCTT
CG96334-02
DNA Sequence	GCACCGTCATTTTCATTCCATGCTGCTCGCCTTCAGATCGCTGGACAGATGCCCCATTCACATCAGT
	ACAGTGACCGTCGCCAGCCAAACATAAGTGACCAACAGGTTTCTGCCTTATCATATTCTGACCAGAT
	TCAGCAACCTCTAACTAACCAGAGGCGGATGCCCCAAACCTTCCGTGACCCAGCAACTGCTCCCCTG
	AGAAAACTTTCTGTTGACTTGATCAAAACATACAAGCATATTAATGAOGAGTACAAACCACCAGGAA
	CCCGTAAACTTCATAACATTCTTGGAGTGGAAACAGGAGGACCTGGTGGGCGACGTGCTGGGGAGTC
	AGGTCATACGGTCGCTCACTACTTGAAGTTCAAAGACCTCATTTTAAGGATGCTTGATTAPGACCCC
	AAAACTCGAATTCAACCTTATTATGCTCTGCAGCACAGTTTCTTCAAGAAAACAGCTGATGAAGGTA
	CAAATACAAGTAATAGTGTATCTACAAGCCCCGCCATGGAGCAGTCTCAGTCTTCGGGCACCACCTC
	CAGTACATCGTCAAGCTCAGGTGGCTCATCGGGGACAAGCAACAGTGGGAGAGCCCGGTCCGATCCG
	ACGCACCAGCATCGGCACAGTGGTGGGCACTTCACAGCTGCCGTGCAGGCCATGGACTGCCAGACAC
	ACAGTCCCCAGGTGCGTCAGCAATTTCCTGCTCCTCTTGGTTGGTCAGGCACTGAAGCTCCTACACA
	GGTCACTGTTGAAACTCATCCTGTTCAAGAAACAACCTTTCATGTAGGCCCTCAACAGAATGCATTG
	CATCATCACCATGGTAACAGTTCCCATCACCATCACCACCACCACCACCATCACCACCACCATGGAC
	AACAAGCCTTGGGTAACCGGACCAGGCCAAGGGTCTACAATTCTCCAACGAATAGCTCCTCTACCCA
	AGATTCTATGGAGGTTGGCCACAGTCACCACTCCATGACATCCCTGTCTTCCTCAACGACTTCTTCC
	TCGACATCTTCCTCCTCTACTGGTAACCAAGGCAATCAGCCCTACCAGAATCGCCCAGTGGCTGCTA
	ATACCTTGGACTTTGGACAGAATGGAGCTATGGACGTTAATTTGACCGTCTACTCCAATCCCCGCCA
	AGAGACTGGCATAGCTGGACATCCAACATACCAATTTTCTGCTAATACAGGTCCTGCACATTACATG
	ACTGAAGGACATCTGACAATGAGGCAAGGGGCTGATAGAGAAGAGTCCCCCATGACAGGAGTTTGTG
	TGCAACAGAGTCCTGTAGCTAGCTCGTGA
	ORF Start: ATG at 17		ORF Stop: TGA at 1367
	SEQ ID NO: 170	450 aa	MW at 48984.0kD
NOV39b,	MHTGGETSACKPSSVRLAPSFSFHAAGLQMAGQMPHSHQYSDRRQPNISDQQVSALSYSDQIQQPLT
CG96334-02
Protein Sequence	NQRPMPQTFRDPATAPLRKLSVDLIKTYKHINEEYKPPGTRKLHNILGVETGGPGGRRAGESGHTVA
	DYLKFKDLILRMLDYDPKTRIQPYYALQHSFFKKTADEGTNTSNSVSTSPAMEQSQSSGTTSSTSSS
	SGGSSGTSNSGRARSDPTHQHRHSGGHFTAAVQAMDCETHSPQVRQQFPAPLGWSGTEAPTQVTVET
	HPVQETTFHVGFQQNALHHHHGNSSHHHHHHHHHHHHHGQQALGNRTRPRVYNSPTNSSSTQDSMEV
	GHSHHSMTSLSSSTTSSSTSSSSTGNQGNQPYQNRPVAANTLDFGQNGAMDVNLTVYSNPRQETGIA
	GHPTYQFSANTGPAHYMTEGHLTMRQGADREESPMTGVCVQQSPVASS

[0561] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 39B.

TABLE 39B
Comparison of NOV39a against NOV39b.
			Identities/
			Similarities for
	Protein	NOV39a Residues/	the Matched
	Sequence	Match Residues	Region
	NOV39b	405 . . . 763	267/359 (74%)
		92 . . . 450	268/359 (74%)

[0562] Further analysis of the NOV39a protein yielded the following properties shown in Table 39C.

TABLE 39C
Protein Sequence Properties NOV39a
PSort     0.9600 probability located in nucleus; 0.1736 probability
analysis: located in lysosome (lumen); 0.1198 probability located
          in microbody (peroxisome); 0.1000 probability located in
          mitochondrial matrix space
SignalP   No Known Signal Sequence Predicted
analysis:

[0563] 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 39D.

TABLE 39D
Geneseq Results for NOV39a
			Identities/
			Similarities for
Geneseq	Protein/Organism/Length	NOV39a Residues/	the Matched	Expect
Identifier	[Patent #, Date]	Match Residues	Region	Value
ABB57155	Mouse ischaemic condition	1 . . . 763	756/763 (99%)	0.0
	related protein sequence SEQ	1 . . . 763	758/763 (99%)
	ID NO: 377 - Mus musculus,
	763 aa. [WO200188188-A2,
	22 NOV. 2001]
AAW41734	Human TRAF-2 kinase -	1 . . . 763	756/763 (99%)	0.0
	Homo sapiens, 763 aa.	1 . . . 763	758/763 (99%)
	[WO9801541-A1,
	15 JAN. 1998]
AAU02221	Human MNB, homologue of	1 . . . 763	755/763 (98%)	0.0
	Drosphila minibrain mnb -	1 . . . 763	757/763 (98%)
	Homo sapiens, 763 aa.
	[US6251664-B1,
	26 JUN. 2001]
AAU02222	Rat Dyrk, a homologue of	1 . . . 763	753/763 (98%)	0.0
	Drosphila minibrain mnb -	1 . . . 763	756/763 (98%)
	Rattus sp, 763 aa.
	[US6251664-B1,
	26 JUN. 2001]
AAM93441	Human polypeptide, SEQ ID	69 . . . 574	376/509 (73%)	0.0
	NO: 3082 - Homo sapiens,	21 . . . 522	429/509 (83%)
	629 aa. [EP1130094-A2,
	05 SEP. 2001]

[0564] 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 39E.

TABLE 39E
Public BLASTP Results for NOV39a
			Identities/
		NOV39a	Similarities
Protein		Residues/	for the
Accession		Match	Matched
Number	Protein/Organism/Length	Residues	Portion	Expect Value
Q61214	Dual-specificity	1 . . . 763	756/763	0.0
	tyrosine-phosphorylation		(99%)
	regulated kinase 1A (EC	1 . . . 763	758/763
	2.7.1.-) (Protein kinase		(99%)
	minibrain homolog) (MNBH)
	(MP86) (Dual specificity
	YAK 1-related kinase) - Mus
	musculus (Mouse); 763 aa.
Q13627	Dual-specificity	1 . . . 763	756/763	0.0
	tyrosine-phosphorylation		(99%)
	regulated kinase 1A (EC	1 . . . 763	758/763
	2.7.1.-) (Protein kinase		(99%)
	minibrain homolog) (MNBH)
	(HP86) (Dual specificity
	YAK 1-related kinase) -
	Homo sapiens (Human),
	763 aa.
Q63470	Dual-specificity	1 . . . 763	755/763	0.0
	tyrosine-phosphorylation		(98%)
	regulated kinase 1A (EC	1 . . . 763	758/763
	2.7.1.-) (Protein kinase		(98%)
	minibrain homolog) (MNBH)
	(RP86) (Dual specificity
	YAK 1-related kinase) -
	Rattus norvegicus (Rat),
	763 aa.
JC4898	Down-syndrome-critical-	1 . . . 763	747/763	0.0
	region protein - human, 754 aa.		(97%)
		1 . . . 754	749/763
			(97%)
CAD30635	Minibrain protein kinase -	1 . . . 763	729/766	0.0
			(95%)
	Gallus gallus (Chicken),	1 . . . 756	739/766
	756 aa.		(96%)

[0565] PFam analysis predicts that the NOV39a protein contains the domains shown in the Table 39F.

TABLE 39F
Domain Analysis of NOV39a
Pfam	NOV39a	Identities/Similarities	Expect
Domain	Match Region	for the Matched Region	Value
pkinase	159 . . . 380	84/235 (36%)	2.8e−51
		170/235 (72%)
pkinase	452 . . . 479	10/31 (32%)	2.7e−05
		22/31 (71%)

Example 40

[0566] The NOV40 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 40A.

TABLE 40A
NOV40 Sequence Analysis
	SEQ ID NO: 171	1186 bp
NOV4a,	GATGTCCGGCTGGAGCTGTCGCCTCCGCCGCCGCTGCTGCCGGTGCCGGTTGTGAGCGGGTCTCCAG
CG96714-01
DNA Sequence	TCGGCTCCTCTGGGCGTCTCATGGCCTCTAGCAGCTCCCTGGTGCCCGACCGGCTGCGCCTGCCGCT
	CTGCTTCCTGGGTGTCTTTGTCTGCTATTTTTACTATCGGATCCTGCAGGAAAAGATAACAAGAGGA
	AAGTATGGGGAAGGAGCCAAGCAGGAGACGTTCACCTTTGCCTTAACTTTGGTCTTCATTCAATGTG
	TGATCAATGCTGTGTTTGCCAAGATCTTGATCCAGTTTTTTGACACTGCCACGGTGGATCGTACCCG
	GAGCTGGCTCTATGCTGCCTGTTCTATCTCCTATCTGGGTGCCATGGTCTCCAGCAATTCAGCACTA
	CAGTTTGTCAACTACCCAACTCAGGTCCTTCGTAAATCCTGCAAGCCAATCCCAGTCATGCTCCTTG
	GGGTGACCCTCTTGAAGAAGAAGTACCCGTTGGCCAAGTACCTGTGTGTGCTGTTAATTGTGGCTGG
	AGTGGCCCTTTTCATGTACAAACCCAAGAAAGTTGTTGGGATAGAAGAACACACAGTCGGCTATGGA
	GAGCTACTCTTGCTATTATCGCTGACCCTCGATGGACTGACTGGTGTTTCCCAGGACCACATGCGGG
	CTCATTACCAAACAGGCTCCAACCACATGATGCTGAACATCAACCTTTGGTCGACATTGCTGCTGCG
	AATGGGAATCCTGTTCACTGGGGAGCTCTGGGAGTTCTTGAGCTTTGCTGAAAGGTACCCTGCCATC
	ATCTATAACATCCTGCTCTTTGGGCTGACCAGTGCCCTGGGTCAGAGCTTCATCTTTATGACGCTTG
	TGTATTTTGGTCCCCTGACCTGCTCCATCATCACTACAACTCGAAAGTTCTTCACAATTTTGGCCTC
	TGTGATCCTCTTCGCCAATCCCATCAGCCCCATGCAGTGGGTGGGCACTGTGCTTGTGTTCCTGGGT
	CTTGGTCTTGATGCCAAGTTTGGGAAAGGACCTAAGAAGACATCCCACTAGGAAGAGAGAGACTACC
	TCCACATCAAGAATATTTAAGTTATTATCTCAAACAGTGACATCTCTTGGGAAAATGGACTTAATAG
	GAATATGGGACTGAGTTCCAGTCTTTTTTAATAAAATAAAATCAAGC
	ORF Start: ATG at 88		ORF Stop: TAG at 1054
	SEQ ID NO: 172	322 aa	MW at 35759.2kD
NOV40a,	MASSSSLVPDRLRLPLCFLGVFVCYFYYGILQEKITRGKYGEGAKQETFTFALTLVFIQCVINAVFA
CG96714-01
Protein Sequence	KILIQFFDTARVDRTRSWLYAACSISYLGAMVSSNSALQFVNYPTQVLGKSCKPIPVMLLGVTLLKX
	KYPLAKYLCVLLIVAGVALFMYKPKKVVGIEEHTVGYGELLLLLSLTLDGLTGVSQDHMRAHYQTGS
	NHMMLNINLWSTLLLGMGILFTGELWEFLSFAERYPAIIYNILLFGLTSALGQSFIFMTVVYFGPLT
	CSIITTTRKFFTILASVILFANPISPMQWVGTVLVFLGLGLDAKFGKGAKKTSH
	SEQ ID NO: 173	1340 bp
NOV40b,	ATTNNAAGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAGAGCTCTCTGGCTAAC
212778987 DNA
Sequence	TAGAGAACCCACTGCTTACTCGCTTATCGAAATTAATACGACTCACTATAGGGAGACCCAAGCTGGC
	TAGCGTTTAAACTTAAGCTTGGTACCGAGCTCGCATCCACTAGTCCAGTGTGGTGGAATTCCACCAT
	CGCCTCTAGCAGCTCCCTGGTGCCCGACCGGCTGCGCCTCCCCCTCTGCTTCCTGGGTGTCTTTGTC
	TGCTATTTTTACTATGGGATCCTGCAGGAAAAGATAACAAGAGGAAAGTATGCGGAAGGAGCCAAGC
	AGGAGACGTTCACCTTTGCCTTAACTTTGGTCTTCATTCAATGTGTGATCAATGCTGTGTTTGCCAA
	GATCTTGATCCAGTTTTTTGACACTGCCAGGGTGGATCGTACCCGGAGCTGGCTCTATGCTGCCTGT
	TCTATCTCCTATCTGGGTGCCATOGTCTCCAGCAATTCAGCACTACAGTTTGTCAACTACCCAACTC
	AGGTCCTTGGTAAATCCTGCAAGCCAATCCCAGTCATGCTCCTTGGGGTGACCCTCTTGAAGAAGAA
	GTACCCGTTCGCCAAGTACCTGTGTGTGCTGTTAATTGTGGCTGGAGTGGCCCTTTTCATGTACAAA
	CCCAAGAAAGTTGTTGGGATAGAAGAACACACAGTCGGCTATGGACAGCTACTCTTGCTATTATCGC
	TGACCCTGGATGGACTGACTGGTGTTTCCCAGGACCACATGCGGGCTCATTACCAAACAGGCTCCAA
	CCACATGATGCTGAACATCAACCTTTCCTCGACATTGCTGCTGGGAATGGGAATCCTGTTCACTGGG
	GAGCTCTGGGAGTTCTTGAGCTTTGCTGAAAGGTACCCTGCCATCATCTATAACATCCTGCTCTTTG
	GGCTGACCAGTGCCCTGGGTCAGAGCTTCATCTTTATGACGGTTGTGTATTTTGGTCCCCTGACCTG
	CTCCATCATCACTACAACTCGAAAGTTCTTCACAATTTTGGCCTCTGTGATCCTCTTCGCCAATCCC
	ATCAGCCCCATGCAGTGGGTGGGCACTGTGCTTGTGTTCCTGGGTCTTGGTCTTGATGCCAAGTTTG
	GGAAAGGAGCTAAGAAGACATCCCACTAGGCGGCCGCTCGAGTCTAGAGGGCCCGTTTAAACCCGCT
	GATCAGCCTCGACTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCCTT
	GACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTCTG
	ORF Start: at 119		ORF Stop: TAG at 1166
	SEQ ID NO: 174	349 aa	MW at 38719.5kD
NOV40b,	GDPSWLAFKLKLGTELGSTSPVWWNSTMASSSSLVPDRLRLPLCFLGVFVCYFYYGILQEKITRGKY
212778987
Protein Sequence	GEGAKQETFTFALTLVFIQCVINAVFAKILIQFFDTARVDRTRSWLYAACSISYLGAMVSSNSALQF
	VNYPTQVLGKSCKPIPVMLLGVTLLKKKYPLAKYLCVLLIVAGVALFMYKPKKVVGIEEHTVGYGEL
	LLLLSLTLDGLTGVSQDHMRAHYQTGSNHMMLNINLWSTLLLGMGILFTGELWEFLSFAERYPAIIY
	NILLFGLTSALGQSFIFMTVVYFGPLTCSIITTTRKFFTILASVILFANPISPMQWVGTVLVFLGLG
	LDAKFGKGAKKTSH
	SEQ ID NO: 175	1025 bp
NOV40c,	GGTCTCCAGTCGGCTCCTCTGGGCGTCTCATGGCCTCTAGCAGCTCCCTGGTGCCCGACCGGCTGCC
CG96714-02
DNA Sequence	CCTGCCGCTCTGCTTCCTGGGTGTCTTTGTCTGCTATTTTTACTATGGGATCCTGCAGGAAAAGATA
	ACAAGAGGAAAGTATGGGGAAGGAGCCAAGCAGGAGACGTTCACCTTTGCCTTAACTTTGGTCTTCA
	TTCAATGTGTGATCAATGCTGTGTTTGCCAAGATCTTGATCCAGTTTTTTGACACTGCCAGGGTGGA
	TCGTACCCGGAGCTGGCTCTATGCTGCCTGTTCTATCTCCTATCTGGGTCCCATGGTCTCCAGCAAT
	TCAGCACTACAGTTTGTCACTACCCAACTCAGGTCCTTGGTAAATCCTGCAAGCCAATCCCATGTCA
	TGCTCCTTGGGGTGACCCTCTTGAAGAAGAAGTACCCGTTGGCCAAGTACCTGTGTGTGCTGTTAAT
	TGTGGCTGGAGTGGCCCTTTTCATGTACAAACCCAAGAAAGTTGTTGGGATAGAAGAACACACAGTC
	GGCTATGGAGAGCTACTCTTGCTATTATCGCTGACCCTGGATGGACTGACTGGTGTTTCCCAGGACC
	ACATGCGGGCTCATTACCAAACAGCCTCCAACCACATGATGCTGAACATCAACCTTTGGTCGACATT
	GCTGCTGGGAATGGGAATCCTGTTCACTGGGGAGCTCTGGGAGTTCTTGAGCTTTGCTGAAAGGTAC
	CCTGCCATCATCTATAACATCCTGCTCTTTCGGCTGACCAGTGCCCTGGGTCAGAGCTTCATCTTTA
	TGACGGTTGTGTATTTTGGTCCCCTGACCTGCTCCATCATCACTACAACTCGAAAGTTCTTCACAAT
	TTTGGCCTCTGTGATCCTCTTCGCCAATCCCATCAGCCCCATGCAGTGGGTGGGCACTGTGCTTGTG
	TTCCTGGGTCTTGGTCTTGATGCCAAGTTTGGGAAAGGAGCTAAGAAGACATCCCACTAGGAAGAGA
	GAGACTACCTCCACATCAAG
	ORF Start: ATG at 30		ORF Stop: TAG at 996
	SEQ ID NO: 176	322 aa	MW at 35759.2kD
NOV4Oc,	MASSSSLVPDRLRLPLCFLGVFVCYFYYGILQEKITRGKYGEGAKQETFTFALTLVFIQCVINAVFA
CG96714-02
Protein Sequence	KILIQFFDTARVDRTRSWLYAACSISYLGAMVSSNSALQFVNYPTQVLGKSCKPIPVMLLGVTLLKK
	KYPLAKYLCVLLIVAGVALFMYKPKKVVGIEEHTVGYGELLLSLTLDGLTGVSQDHHYERAHYQTGS
	NHMMLNINLWSTLLLGMGILFTGELWEFLSFAERYPAIIYNILLFGLTSALGQSFIFMTVVYFGPLT
	CSIITTTRKFFTILASVILFANPISPMQWVGTVLVFLGLGLDAXFGKGAKKTSH
	SEQ ID NO: 177	975 bp
NOV4Od,	CCAGAATTCCACCATGGCCTCTAGCACCTCCCTGGTGCCCGACCGGCTGCGCCTGCCGCTCTGCTTC
190235426 DNA
Sequence	CTGGGTGTCTTTGTCTGCTATTTTTACTATGGGATCCTGCAGGAAAAGATAACAAGAGGAAAGTATG
	GGGAAGGAGCCAAGCAGGAGACGTTCACCTTTGCCTTAACTTTGGTCTTCATTCAATGTGTGATCAA
	TGCTGTGTTTGCCAAGATCTGGTGGATCGTACCCGGAGCTGGCTCTATGCTGCCTGTTCTATCTCCT
	ATCTGGGTGCCATGGTCTCCAGCAATTCAGCACTACAGTTTGTCAACTACCCAACTCAGGTCCTTGG
	TAAATCCTGCAAGCCAATCCCAGTCATGCTCCTTGGGGTGACCCTCTTGAAGAAGAAGTACCCGTTG
	GCCAAGTACCTGTGTGTGCTGTTAATTGTGCCTGGAGTGGCCCTTTTCATGTACAAACCCAAGAAAG
	TTGTTGGGATAGAAGAACACACAGTCGGCTATGGAGAGCTACTCTTGCTATTATCGCTGACCCTGGA
	TGGACTGACTAGTGTTTCCCAGGACCACATGCGGGCTCATTACCAAACAGGCTCCAACCACATGATG
	CTGAACATCAACCTTTGGTCGACATTGCTGCTGGGAATGGGAATCCTGTTCACTGCGGAGCTCTGGG
	AGTTCTTGAGCTTTGCTGAAAGGTACCCTGCCATCATCTATAACATCCTGCTCTTTGGGCTGACCAG
	TGCCCTGGGTCAGAGCTTCATCTTTATGACGGTTGTGTATTTTGGTCCCCTGACCTGCTCCATCATC
	ACTACAACTCGAAAGTTCTTCACAATTTTGGCCTCTGTGATCCTCTTCGCCAATCCCATCAGCCCCA
	TGCAGTGGGTGGGCACTGTGCTTGTGTTCCTTGGTCTTGGTCTTGATGCCAAGTTTGGGAAAGGAGC
	TAAGAAGACATCCCACTAGGCGCCCCCTTTTTTCCTT
	ORF Start: at 25		ORF Stop: TAG at 955
	SEQ ID NO: 178	310 aa	MW at 34026.1kD
NOV4Od,	QLPGARPAAPAALLPGCLCLLFLLWDPAGKDNXRKVWGRSQAGDVELCLNFGLHSMCDQCCVCQDLV
190235426
Protein Sequence	DRTRSWLYAACSISYLGAMVSSNSALQFVNYPTQVLGKSCKPIPVMLLGVTLLKKKYFLAKYLCVLL
	IVAGVALFNYKPKKVVGTEEHTVGYGELLLLLSLTLDGLTGVSQDHMRAHYQTGSNHMMLNTNLWST
	LLLGMGILFTGELWEFLAFAERYPAIIYNILLFGLTSALGQSFIFMTVVYFGPLTCSIITTTRKFFT
	ILASVILFANPISPMQWVGTVLVFLGLGLDAKFGKGAIKKTSH
	SEQ ID NO: 179	1025 bp
NOV40e,	GGTCTCCAGTCGGCTCCTCTGGGCGTCTCATGGCCTCTAGCAGCTCCCTGGTGCCCGACCGGCTGCG
CG96714-03
DNA Sequence	CCTGCCGCTCTGCTTCCTGGGTGTCTTTGTCTGCTATTTTTACTATGGGATCCTGCAGGAAAAGATA
	ACAAGAGGAAAGTATGGGGAAGGAGCCAAGCAGGAGACGTTCACCTTTGCCTTAACTTTGGTCTTCA
	TTCAATGTGTGATCAATGCTGTGTTTGCCAAGATCTTGATCCAGTTTTTTGACACTGCCACGGTGGA
	TCGTACCCGGAGCTGGCTCTATGCTGCCTGTTCTATCTCCTATCTGGGTGCCATGGTCTCCAGCAAT
	TCAGCACTACAGTTTGTCAACTACCCAACTCAGGTCCTTGGTAAATCCTGCAAGCCAATCCCAGTCA
	TGCTCCTTGGGGTGACCCTCTTGAAGAAGAAGTACCCGTTGGCCAAGTACCTGTGTGTGCTGTTAAT
	TGTGGCTGGAGTGGCCCTTTTCATGTACAAACCCAAGAAAGTTGTTGGGATAGAAGAACACACAGTC
	GGCTATGGAGAGCTACTCTTGCTATTATCGCTGACCCTGGATGGACTGACTGGTGTTTCCCAGGACC
	ACATGCGGGCTCATTACCAAACAGGCTCCAACCACATGATGCTGAACATCAACCTTTGGTCGACATT
	GCTGCTGGGAATGGGAATCCTGTTCACTGGCGAGCTCTGGGAGTTCTTGAGCTTTGCTGAAAGGTAC
	CCTGCCATCATCTATAACATCCTGCTCTTTGGGCTGACCAGTGCCCTGGGTCAGAGCTTCATCTTTA
	TGACGGTTGTGTATTTTGGTCCCCTGACCTGCTCCATCATCACTACAACTCGAAAGTTCTTCACAAT
	TTTGGCCTCTGTGATCCTCTTCGCCAATCCCATCAGCCCCATGCAGTCGGTGGGCACTGTGCTTGTG
	TTCCTGGGTCTTGGTCTTGATGCCAAGTTTCGGAAAGGAGCTAAGAAGACATCCCACTAGGAAGAGA
	GAGACTACCTCCACATCAAG
	ORF Start: ATG at 30		ORF Stop: TAG at 996
	SEQ ID NO: 180	322 aa	MW at 35759.2kD
NOV40e,	MASSSSLVPDRLRLPLCFLGVFVCYFYYGILQEKITRGKYGEGAKQETFTFALTLVFIQCVINAVFA
CG96714-03
Protein Sequence	KILIQFFDTARVDRTRSWLYAACSISYLGAMVSSNSALQFVNYPTQVLGKSCKPIPVMLLGVTLLKK
	KYPLAKYLCVLLIVALVALFMYKPKKVVGIEEHTVGYGELLLLLSLTLDGLTGVSQDHMRAHYQTGS
	NHMMLNINLWSTLLLGMGILFTGELWEFLSFAERYPAIIYNILLFGLTSALGQSFIFMTVVYFGPLT
	CSIITTTRKFFTILASVILFANPISPMQWVGTVLVFLGLGLDAKFGKGAKKTSH

[0567] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 40B.

TABLE 40B
Comparison of NOV40a against NOV40b through NOV40e.
	Protein	NOV40a Residues/	Identities/Similarities
	Sequence	Match Residues	for the Matched Region
	NOV40b	1 . . . 322	284/322 (88%)
		28 . . . 349	284/322 (88%)
	NOV40c	1 . . . 322	284/322 (88%)
		1 . . . 322	284/322 (88%)
	NOV40d	81 . . . 322	204/242 (84%)
		69 . . . 310	204/242 (84%)
	NOV40e	1 . . . 322	284/322 (88%)
		1 . . . 322	284/322 (88%)

[0568] Further analysis of the NOV40a protein yielded the following properties shown in Table 40C.

TABLE 40C
Protein Sequence Properties NOV40a
PSort     0.6850 probability located in endoplasmic reticulum
analysis: (membrane); 0.6400 probability located in plasma
          membrane; 0.4600 probability located in Golgi body;
          0.1000 probability located in endoplasmic reticulum (lumen)
SignalP   Cleavage site between residues 68 and 69
analysis:

[0569] A search of the NOV40a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 40D.

TABLE 40D
Geneseq Results for NOV40a
		NOV40a	Identities/
		Residues/	Similarities
Geneseq	Protein/Organism/Length	Match	for the	Expect
Identifier	[Patent #, Date]	Residues	Matched Region	Value
AAB43476	Human cancer associated	1 . . . 322	322/322 (100%)	0.0
	protein sequence SEQ ID	51 . . . 372	322/322 (100%)
	NO:921 - Homo sapiens, 372
	aa. [WO200055350-A1,
	21 SEP. 2000]
ABG25333	Novel human diagnostic	30 . . . 220	184/191 (96%)	e−103
	protein #25324 - Homo	114 . . . 304	187/191 (97%)
	sapiens, 846 aa.
	[WO200175067-A2,
	11 OCT. 2001]
ABB61815	Drosophila melanogaster	8 . . . 317	159/315 (50%)	1e−84
	polypeptide SEQ ID NO	3 . . . 316	212/315 (66%)
	12237 - Drosophila
	melanogaster, 338 aa.
	[WO200171042-A2,
	27 SEP. 2001]
AAG04835	Arabidopsis thaliana protein	1 . . . 307	114/315 (36%)	3e−44
	fragment SEQ ID NO: 1012 -	1 . . . 311	171/315 (54%)
	Arabidopsis thaliana, 329 aa.
	[EP1033405-A2,
	06 SEP. 2000]
AAG07182	Arabidopsis thaliana protein	12 . . . 307	101/302 (33%)	5e−41
	fragment SEQ ID NO: 4238 -	12 . . . 311	161/302 (52%)
	Arabidopsis thaliana, 332 aa.
	[EP1033405-A2,
	06 SEP 2000]

[0570] In a BLAST search of public sequence datbases, the NOV40a protein was found to have homology to the proteins shown in the BLASTP data in Table 40E.

TABLE 40E
Public BLASTP Results for NOV40a
		NOV40a	Identities/
Protein		Residues/	Similarities
Accession		Match	for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
P78383	UGTrel1 - Homo sapiens	1 . . . 322	322/322 (100%)	0.0
	(Human), 322 aa.	1 . . . 322	322/322 (100%)
Q96EW7	Similar to UDP-galactose	1 . . . 322	321/322 (99%)	0.0
	transporter related - Homo	1 . . . 322	321/322 (99%)
	sapiens (Human), 322 aa.
CAD33236	Putative endoplasmic	1 . . . 322	314/322 (97%)	0.0
	reticulum nucleotide sugar	34 . . . 355	320/322 (98%)
	transporter - Bos taurus
	(Bovine), 355 aa.
P70639	UGTrel1 - Rattus rattus	1 . . . 322	309/322 (95%)	e−179
	(Black rat), 322 aa.	1 . . . 322	316/322 (97%)
P97858	UGTREL1 (Solute carrier	1 . . . 322	308/322 (95%)	e−178
	family 35 (UDP-galactose	1 . . . 322	315/322 (97%)
	transporter), member 2) -
	Mus musculus (Mouse), 322
	aa.

[0571] PFam analysis predicts that the NOV40a protein contains the domains shown in the Table 40F.

TABLE 40F
Domain Analysis of NOV40a
Pfam	NOV40a	Identities/Similarities	Expect
Domain	Match Region	for the Matched Region	Value
DUF6	23 . . . 156	25/140 (18%)	0.049
		97/140 (69%)
DUF6	181 . . . 312	29/135 (21%)	0.006
		91/135 (67%)

Example 41

[0572] The NOV41 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 41A.

TABLE 41A
NOV41 Sequence Analysis
	SEQ ID NO: 181	1650 bp
NOV41a,	CCTTCACACAGCTCTTTCACCATGCCTGGATCACTTCCTTTGAATGCAGAAGCTTGCTGGCCAAAAG
CG97025-01
DNA Sequence	ATGTTGGGATTGTTGCCCTTGAGATCTATTTTCCTTCTCAATATGTTGATCAAGCAAAGTTGGAAAA
	ATATGATGGTGTAGATGCTGGGAAGTATACCATTGGCTTGGGCCAGGCCAACATGGGCTTCTGCACA
	GATAGAGAAGATATTAACTCTCTTTGCATGACTGTGGTTCAGAATCTTATGGAGAGAAATAACCTTT
	CCTATGATTGCATTGGGCGGCTGGAAGTTGGAACAGAGACAATCATCGACAAATCAAAGTCTGTGAA
	GACTAATTTGATGCAGCTGTTTGAAGAGTCTGGGAATACAGATATAGAAGGAATCGACACAACTAAT
	GCATGCTATGGAGGCACAGCTGCTGTCTTCAATGCTGTTAACTGGATTGAGTCCAGCTCTTGCGATG
	GACGGTATGCCCTGGTAGTTGCAGGAGATATTGCTGTATATGCCACAGGAAATGCTAGACCTACAGG
	TGGAGTTGGAGCAGTAGCTCTGCTAATTGGGCCAATGCTCCTTTAATTTTTGAACGAGGGCTTCGT
	GGGACACATATGCAACATGCCTATGATTTTTACAAGCCTGATATGCTATCTGAATATCCTATAGTAG
	ATGGGAAACTCTCCATACAGTGCTACCTCAGTGCATTAGACCGCTGCTATTCTGTCTACTGCAAAAA
	GATCCATGCCCAGTGGCAGAAAGAGGGAAATGATAAAGATTTTACCTTGAATGATTTTGGCTTCATG
	ATCTTTCACTCACCATATTGTAAACTGGTTCAGAAATCTCTAGCTCGGATGTTGCTGAATGACTTCC
	TTAATGACCACAATAGAGATAAAAATAGTATCTATAGTGGCCTGGAAGCCTTTGGGGATGTTAAATT
	AGAAGACACCTACTTTGATAGAGATGTGGAGAAGGCATTTATGAAGGCTAGCTCTGAACTCTTCAGT
	CAGAAAACAAACGCATCTTTACTTGTATCAAATCAAAATGGAAATATGTACACATCTTCAGTATATG
	GTTCCCTTGCATCTGTTCTAGCACAGTACTCACCTCAGCAATTAGCAGGGAAGAGAATTGGAGTGTT
	TTCTTATGGTTCTGGTTTGGCTGCCACTCTGTACTCTCTTAAAGTCACACAAGATGCTACACCGGGG
	TCTGCTCTTGATAAAATAACAGCAAGTTTATGTGATCTTAAATCAAGGCTTGATTCAAGAACTGGTG
	TGGCACCAGATGTCTTCGCTGAAAACATGAAGCTCAGAGAGGACACCCATCATTTGGTCAACTATAT
	TCCCCAGGGTTCAATAGATTCACTCTTTGAAGGAACGTGGTACTTAGTTAGGGTCGATGAAAAGCAC
	AGAAGAACTTACGCTCGGCGTCCCACTCCAAATGATGACACTTTGGATGAAGGAGTAGGACTTGTGC
	ATTCAAACATAGCAACTGAGCATATTCCAAGCCCTGCCAAGAAAGTACCAAGACTCCCTGCCACAGC
	AGCAGAACCTGAAGCAGCTGTCATTAGTAATGGGGAACATTAAGATACTCTGTGAGGTGCAAGACTT
	CAGGGTGGGGTGGGCATGGGGTGGGGGTATGGGAACAGTTGG
	ORF Start: ATG at 22		ORF Stop: TAA at 1582
	SEQ ID NO: 182520 aa	MW at 57293.0kD
NOV41a,	MPGSLPLNAEACWPKDVGIVALEIYFPSQYVDQAELEKYDGVDAGKYTIGLGQAXMGFCTDREDINS
CG97025-01
Protein Sequence	LCMTVVQNLMERNNLSYDCIGRLEVGTETIIDKSKSVKTNLMQLFEESGNTDIEGIDTTNACYGGTA
	AVFNAVNWIESSSWDGRYALVVAGDIAVYATGNARPTGGVGAVALLIGPNAPLIFERGLRGTHMQHA
	YDFYXPDMLSEYPIVDGKLSIQCYLSALDRCYSVYCKKIHAQWQKEGNDKDFTLNDFGFMIFMSPYC
	KLVQKSLARMLLNDFLNDQNRDKNSIYSGLEAFGDVKLEDTYFDRDVEKAFMKASSELFSQKTKASL
	LVSNQNGNWITSSVYGSLASVLAQYSPQQLAGKRIGVFSYGSGLAATLYSLKVTQDATPGSALDKIT
	ASLCDLKSRLDSRTGVAPDVFAENIKLREDTHHLVNYIPQGSIDSLFEGTWYLVRVDEKHRRTYARR
	PTPNDDTLDEGVGLVHSMIATEHIPSPAKKVPRLPATAAEPEAAVISNGEH
	SEQ ID NO: 183	1650 bp
NOV41b,	CCTTCACACAGCTCTTTCACCATGCCTGGATCACTTCCTTTGAATGCAGAAGCTTGCTGGCCAAAAG
CG97025-01
DNA Sequence	ATGTTGGGATTGTTGCCCTTGAGATCTATTTTCCTTCTCAATATGTTGATCAAGCAGAGTTGGAAAA
	ATATGATGGTGTAGATGCTGGGAAGTATACCATTGGCTTGGGCCAGGCCAAGATGGCCTTCTGCACA
	GATAGAGAAGATATTAACTCTCTTTGCATGACTGTGGTTCAGAATCTTATGGAGAGAAATAACCTTT
	CCTATGATTGCATTGGGCGGCTGGAAGTTGGAACAGAGACAATCATCGACAAATCAAAGTCTGTGAA
	GACTAATTTGATGCAGCTGTTTGAAGAGTCTGGGAATACAGATATAGAAGGAATCGACACAACTAAT
	GCATGCTATGGAGGCACAGCTGCTGTCTTCAATGCTGTTAACTGGATTGAGTCCAGCTCTTGGGATG
	GACGGTATGCCCTGGTAGTTGCAGGAGATATTGCTGTATATGCCACAGGAAATGCTAGACCTACAGG
	TGGAGTTGGAGCAGTAGCTCTGCTAATTGGGCCAAATGCTCCTTTAATTTTTGAACGAGGGCTTCGT
	GGGACACATATGCAACATGCCTATGATTTTTACAAGCCTGATATGCTATCTGAATATCCTATAGTAG
	ATGGGAAACTCTCCATACAGTGCTACCTCAGTGCATTAGACCGCTGCTATTCTGTCTACTGCAAAAA
	GATCCATGCCCAGTGGCAGAAAGAGCGAAATGATAAAGATTTTACCTTGAATGATTTTGGCTTCATG
	ATCTTTCACTCACCATATTGTAAACTGGTTCAGAAATCTCTAGCTCGGATGTTGCTGAATGACTTCC
	TTAATGACCAGAATAGAGATAAAAATAGTATCTATAGTCGCCTGGAAGCCTTTGGGGATGTTAAATT
	AGAAGACACCTACTTTGATAGAGATGTGGAGAAGGCATTTATGAAGGCTAGCTCTGAACTCTTCAGT
	CAGAAAACAAAGGCATCTTTACTTGTATCAAATCAAAATGGAAATATGTACACATCTTCAGTTTATG
	GTTCCCTTGCATCTGTTCTAGCACAGTACTCACCTCAGCAATTAGCAGGGAAGAGAATTGGAGTGTT
	TTCTTATGGTTCTGGTTTGGCTGCCACTCTGTACTCTCTTAAAGTCACACAAGATGCTACACCGGGG
	TCTGCTCTTGATAAAATAACAGCAAGTTTATGTGATCTTAAATCAAGGCTTGATTCAAGAACTGGTG
	TGGCACCAGATGTCTTCGCTGAAAACATGAAGCTCAGAGAGGACACCCATCATTTGGTCAACTATAT
	TCCCCAGGGTTCAATAGATTCACTCTTTGAAGGAACGTGGTACTTAGTTAGGGTGGATGAAAAGCAC
	AGAAGAACTTACGCTCGGCGTCCCACTCCAAATGATGACACTTTGGATGAAGGAGTAGGACTTGTGC
	ATTCAAACATAGCAACTGAGCATATTCCAAGCCCTGCCAAGAAAGTACCAAGACTCCCTGCCACAGC
	AGCACAACCTGAAGCAGCTGTCATTAGTAATGCGGAACATTATGATACTCTCTGAGGTGCAAGACTT
	CAGGGTGGGGTGGGCATGGGGTGGGGGTATGGCAACAGTTGG
	ORE Start: ATG at 22		ORF Stop: TAA at 1582
	SEQ ID NO: 184	520 aa	MW at 57293.0kD
NOV41b,	MPGSLPLNAEACWPKDVGIVALEIYFPSQYVDQAELEKYDGVDAGKYTIGLGQAKMGFCTDREDINS
CG97025-01
Protein Sequence	LCMTVVQNLMERNNLSYDCIGRLEVGTETIIDKSKSVKTNLMQLFEESGNTDIEGIDTTNACYGGTA
	AVFNAVNWIESSSWDGRYALVVAGDIAVYATGNARPTGGVGAVALLIGPNAPLIFERGLRGTHNQHA
	YDFYKPDMLSEYPIVDGKLSIQCYLSALDRCYSVYCKKIHAQWQKEGNDKDFTLNDFGFMTKHSPYC
	KLVQKSLARMLLNDFLNDQNRDKNSIYSGLEAFGDVKLEDTYFDRDVEKAFMKASSELFSQKTKASL
	LVSNQNGNMYTSSVYGSLASVLAQYSPQQLAGKRIGVFSYGSGLAATLYSLKVTQDATPGSALDKIT
	ASLCDLKSRLDSRTGVAPDVFAENMKLREDTHHLVNYIPQGSIDSLFEGTWYLVRVDEKHRRTYARR
	PTPNDDTLDEGVGLVHSNIATEHIPSPAKKVPRLPATAAEPEAAVISNGEH
	SEQ ID NO: 185	1650 bp
NOV41c,	CCTTCACACAOCTCTTTCACCATGCCTGGATCACTTCCTTTGAATGCAGAAGCTTGCTGGCCAAAAG
CG97025-01
DNA Sequence	ATGTTGGGATTGTTGCCCTTGAGATCTATTTTCCTTCTCAATATGTTGATCAAGCAGAGTTGGAAAA
	ATATGATGGTGTAGATGCTGGGAAGTATACCATTGGCTTGGGCCAGGCCAAGATGGGCTTCTGCACA
	GATAGAGAAGATATTAACTCTCTTTGCATGACTGTGGTTCAGAATCTTATGGAGAGAAATAACCTTT
	CCTATGATTGCATTGGGCGGCTGGAAGTTGGAACAGAGACAATCATCGACAAATCAAAGTCTGTGAA
	GACTAATTTGATGCAGCTGTTTGAAGAGTCTGGGAATACAGATATAGAAGGAATCGACACAACTAAT
	GCATGCTATGGAGGCACAGCTGCTGTCTTCAATGCTGTTAACTGGATTGAGTCCAGCTCTTGGGATG
	GACGGTATGCCCTCGTAGTTGCAGGAGATATTGCTGTATATGCCACAGGAAATGCTAGACCTACAGG
	TGGAGTTGGAGCAGTAGCTCTGCTAATTGGGCCAAATGCTCCTTTAATTTTTGAACGAGGGCTTCGT
	GGGACACATATGCAACATGCCTATGATTTTTACAAGCCTGATATGCTATCTGAATATCCTATAGTAG
	ATGGGAAACTCTCCATACAGTGCTACCTCAGTGCATTAGACCGCTGCTATTCTGTCTACTGCAAAAA
	GATCCATGCCCAGTCCCAGAAAGAGGGAAATGATAAAGATTTTACCTTGAATGATTTTGGCTTCATG
	ATCTTTCACTCACCATATTGTAAACTGGTTCAGAAATCTCTAGCTCGGATGTTGCTGAATGACTTCC
	TTAATGACCAGAATAGAGATAAAAATAGTATCTATAGTCGCCTGGAAGCCTTTGGGGATGTTAAATT
	AGAAGACACCTACTTTGATAGAGATGTGGAGAAGGCATTTATGAAGGCTAGCTCTGAACTCTTCAGT
	CAGAAAACAAAGGCATCTTTACTTGTATCAAATCAAAATGGAAATATGTACACATCTTCAGTATATG
	GTTCCCTTGCATCTGTTCTAGCACAGTACTCACCTCAGCAATTAGCAGGGAAGAGAATTGGAGTGTT
	TTCTTATGGTTCTGGTTTGGCTGCCACTCTGTACTCTCTTAAAGTCACACAAGATGCTACACCGGGG
	TCTGCTCTTGATAAAATAACAGCAAGTTTATGTGATCTTAAATCAAGGCTTGATTCAAGAACTGGTG
	TGGCACCAGATGTCTTCGCTGAAAACATGAAGCTCAGAGAGGACACCCATCATTTGGTCAACTATAT
	TCCCCAGGGTTCAATAGATTCACTCTTTGAAGGAACGTGGTACTTAGTTAGGGTGGATGAAAAGCAC
	AGAAGAACTTACGCTCGGCGTCCCACTCCAAATGATGACACTTTGGATGAAGGAGTACGACTTGTGC
	ATTCAAACATAGCAACTGAGCATATTCCAAGCCCTCCCAAGAAAGTACCAAGACTCCCTGCCACAGC
	AGCAGAACCTGAAGCAGCTGTCATTAGTAATGGGGAACATTAGGATACTCTGTGAGGTGCAAGACTT
	CAGGGTGGGGTGGGCATGGGGTGGGGGTATGGGAACAGTTGG
	ORF Start: ATG at 22		ORF Stop: TAA at 1582
	SEQ ID NO: 186	520 aa	MW at 57293.0kD
NOV41c,	MPGSLPLNAEACWPKDVGIVALEIYFPSQYVDQAELEKYDGVDAGKYTIGLGQAKMGFCTDREDINS
CG97025-01
Protein Sequence	LCMTVVQNLMERNNLSYDCIGRLEVGTETIIDKSKSVKTNLMQLFEESGNTDIEGIDTTNACYGGTA
	AVFNAVNWIESSSWDGRYALVVAGDIAVYATGNARPTGGVGAVALLIGPNAPLIFERGLRGTHMQHA
	YDFYKPDNLSEYPIVDGKLSIQCYLSALDRCYSVYCKKIHAQWQKEGNDKDFTLNDFGFMIFHSPYC
	KLVQKSLARMLLNDFLNDQNRDHNSIYSGLEAFGDVKLEDTYFDRDVEKAFMKASSELFSQKTKASL
	LVSNQNGNMYTSSVYGSLASVLAQYSPQQLAGKRIGVFSYCSGLAATLYSLKVTQDATPGSALDKIT
	ASLCDLKSRLDSRTGVAPDVFAENMXLREDTHHLTNYIPQGSIDSLFEGTWYLVRVDEKHRRTYARR
	PTPNDDTLDEGVGLVHSNIATEHI PSPAKKVPRLPATAAEPEAAVISNGEH
	SEQ ID NO: 187	1593 bp
NOV41d,	CCTGGATCACTTCCTTTGAATGCAGAAGCTTGCTGGCCAAAAGATGTGGGAATTGTTGCCCTTGAGA
254869578 DNA
Sequence	TCTATTTTCCTTCTCAATATGTTGATCAAGCAGACTTGGAAAAATATGATGGTGTAGATGCTGGAAA
	GTATACCATTCGCTTGGGCCAGGCCAAGATGGGCTTCTGCACAGATAGAGAAGATATTAACTCTCTT
	TGCATGACTGTGGTTCAGAATCTTATGGAGAGAAATAACCTTTCCTATGATTGCATTGGGCGGCTGG
	AAGTTGGAACAGACACAATCATCGACAAATCAAAGTCTGTGAAGACTAATTTGATGCAGCTGTTTGA
	AGAGTCTGGGAATACAGATATAGAAGGAATCGACACAACTAATGCATGCTATGGAGGCACAGCTGCT
	GTCTTCAATGCTGTTAACTGGATTGAGTCCAGCTCTTGGGATGGACGGTATGCCCTGGTAGTTGCAG
	GAGATATTGCTGTATATGCCACAGGAAATGCTAGACCTACAGGTGGAGTTGGAGCAGTAGCTCTGCT
	AATTGGGCCAAATGCTCCTTTAATTTTTGAACGAGGGCTTCGTGGGACACATATGCAACATGCCTAT
	GATTTTTACAAGCCTGATATGCTATCTGAATATCCTATAGTAGATGGAAAACTCTCCATACAGTGCT
	ACCTCAGTGCATTAGACCGCTGCTACTCTGTCTACTGCAAAAAGATCCATGCCCAGTGGCAGAAAGA
	GGGAAATGATAAAGATTTTACCTTGAATGATTTTGGCTTCATGATCTTTCACTCACCATATTGTAAA
	CTGGTTCAGAAATCTCTAGCTCGGATGTTGCTGAATGACTTCCTTAATGACCAGAATAGAGATAAaxA
	ATAGTATCTATAGTGGCCTGGAAGCCTTTGGGGATGTTAAATTAGAAGACACCTACTTTGATAGAGA
	TGTGGAGAAGGCATTTATGAAGGCTAGCTCTGAACTCTTCAGTCAGAAAACAAAGGCATCTTTACTT
	GTATCAAATCAAAATGGAAATATGTACACATCTTCAGTATATGGTTCCCTTGCATCTGTTCTAGCAC
	AGTACTCACCTCAGCAATTAGCAGGGAAGAGAATTGCAGTGTTTTCTTATGGTTCTGGTTTGGCTGC
	CACTCTGTACTCTCTTAAAGTCACACAAGATGCTACACCGGGGTCTGCTCTTGATAAAATAACAGCA
	AGTTTATGTGATCTTAAATCAAGGCTTGATTCAAGAACTGGTGTCGCACCAGATGTCTTCGCTGAAA
	ACATGAAGCTCAGAGAGGACACCCATCATTTGGTCAACTATATTCCCCAGGGTTCAATAGATTCACT
	CTTTGAAGGAACGTCGTACTTAGTTAGGGTGGATGAAAAGCACAGAAGAACTTACGCTCGGCGTCCC
	ACTCCAAATGATGACACTTTGGATGAAGGAGTAGGACTTGTGCATTCAAACATAGCAACTGAGCATA
	TTCCAAGCCCTGCCAAGAAAGTACCAAGACTCCCTGCCACAGCAGCAGAACCTGAAGCAGCTGTCAT
	TAGTAATGGGGAACATTAAGCGGCCGCACTCGAGCACCACCACCACCACCAC
	ORF Start: at 1		ORF Stop: TAA at 1558
	SEQ ID NO: 188	519 aa	MW at 57161.8kD
NOV41d,	PGSLPLNAEACWPKDVGIVALEIYFPSQYVDQAELEKYDGVDAGKYTIGLGQAKMGFCTDREDINSL
254869578
Protein Sequence	CMTVVQNLMERNNLSYDCIGRLEVGTETIIDKSKSVKTNLMQLFEESGNTDIECIDTTNACYGGTAA
	VFNAVNWIESSSWDGRYALVVAGDIAVYATGNARPTGGVGAVALLIGPNAPLIFERGLRGTHMQHAY
	DFYXPDMLSEYPIVDGKLSIQCYLSALDRCYSVYCKKIHAQWQKEGNDKDFTLNDFGFMIFHSPYCK
	LVQKSLARMLLNDFLNDQNRDKNSIYSGLEAFGDVKLEDTYFDRDVEKAFMKASSELFSQKTKASLL
	VSNQNGNMYTSSVYGSLASVLAQYSPQQLAGKRIGVFSYGSGLAATLYSLKVTQDATPGSALDKITA
	SLCDLKSRLDSRTGVAPDVFAENNKLREDTHHLVNYIPQGSIDSLFEGTWYLVRVDEKHRRTYARRP
	TPNDDTLDEGVGLVHSNIATEHIPSPAKKVPRLPATAAEPEAAVISNGEH
	SEQ ID NO: 189	1650 bp
NOV41e,	CCTTCACACAGCTCTTTCACCATGCCTGGATCACTTCCTTTGAATGCACAAGCTTGCTGGCCAAAAG
CG97025-01
DNA Sequence	ATGTTGGGATTGTTGCCCTTGAGATCTATTTTCCTTCTCAATATGTTGATCAAGCAGAGTTGGAAAA
	ATATGATGGTGTAGATGCTGGGAACTATACCATTGGCTTGGGCCAGGCCAAGATGGGCTTCTGCACA
	GATAGAGAAGATATTAACTCTCTTTGCATGACTGTGGTTCAGAATCTTATGGAGAGAAATAACCTTT
	CCTATGATTGCATTGGCCGGCTGGAAGTTGGAACAGAGACAATCATCGACAAATCAAAGTCTGTGAA
	GACTAATTTGATGCAGCTGTTTGAAGAGTCTGGGAATACAGATATAGAAGGAATCGACACAACTAAT
	GCATGCTATGGAGGCACAGCTGCTGTCTTCAATGCTCTTAACTGGATTGAGTCCAGCTCTTGGGATG
	GACGGTATGCCCTGGTAGTTGCAGGAGATATTGCTGTATATGCCACAGGAAATGCTAGACCTACAGG
	TGCAGTTGGAGCAGTAGCTCTGCTAATTCGGCCAAATGCTCCTTTAATTTTTGAACGAGGGCTTCGT
	GGGACACATATGCAACATGCCTATGATTTTTACAAGCCTGATATGCTATCTGAATATCCTATAGTAG
	ATGGGAAACTCTCCATACAGTGCTACCTCACTGCATTAGACCGCTGCTATTCTGTCTACTGCAAAAA
	GATCCATGCCCAGTGCCAGAAAGAGGGAAATGATAAAGATTTTACCTTGAATGATTTTGGCTTCATG
	ATCTTTCACTCACCATATTGTAAACTGGTTCAGAAATCTCTAGCTCGGATGTTGCTGAATGACTTCC
	TTAATGACCAGAATAGAGATAAAAATAGTATCTATAGTGGCCTGGAAGCCTTTGGGGATGTTAAATT
	AGAAGACACCTACTTTGATAGAGATGTGGAGAAGGCATTTATGAAGGCTAGCTCTGAACTCTTCAGT
	CAGAAAACAAAGGCATCTTTACTTGTATCAAATCAAAATGGAAATATGTACACATCTTCAGTATATG
	GTTCCCTTGCATCTGTTCTAGCACAGTACTCACCTCAGCAATTAGCAGGGAAGAGAATTGGAGTGTT
	TTCTTATGGTTCTGGTTTGGCTGCCACTCTGTACTCTCTTAAAGTCACACAAGATGCTACACCGGGG
	TCTGCTCTTGATAAAATAACAGCAAGTTTATGTGATCTTAAATCAAGGCTTGATTCAAGAACTGGTG
	TGGCACCAGATGTCTTCGCTGAAAACATGAAGCTCAGAGAGGACACCCATCATTTGGTCAACTATAT
	TCCCCAGGGTTCAATAGATTCACTCTTTOAAGGAACGTGGTACTTAGTTAGGGTGGATGAAAAGCAC
	AGAAGAACTTACGCTCCGCGTCCCACTCCAAATGATGACACTTTGGATGAAGGAGTAGGACTTGTGC
	ATTCAAACATAGCAACTGAGCATATTCCAAGCCCTGCCAAGAAAGTACCAAGACTCCCTGCCACAGC
	AGCAGAACCTCAAGCAGCTGTCATTAGTAATGGGGAACATTAAGATACTCTGTGAGGTGCAAGACTT
	CAGGGTGGGGTGGGCATGGGGTGGGGGTATGGGAACAGTTGG
	ORF Start: ATG at 22		ORF Stop: TAA at 1582
	SEQ ID NO: 190	520 aa	MW at 57293.OkD
NOV41e,	MPGSLPLNAEACWPKDVGIVALEIYFPSQYVDQAELEKYDGVDAGKYTIGLGQAKMGFCTDREDINS
CG97025-01
Protein Sequence	LCMTVVQNLMERNNLSYDCIGRLEVGTETIIDKSKSVKTNLMQLFEESGNTDIEGIDTTNACYGGTA
	AVFNAVNWIESSSWDGRYALVVAGDIAVYATGNARPTGGVGAVALLIGPNAPLIFERGLRGTHMQHA
	YDFYKPDMLSEYPIVDGKLSIQCYLSALDRCYSVYCKKIHAQWQKEGNDKDFTLNDFGFMIFHSPYC
	KLVQKSLARMLLNDFLNDQHRDKNSIYSGLEAFGDVKLEDTYFDRDVEKAFMKASSELFSQKTKASL
	LVSNQNGNMYTSSVYGSLASVLAQYSPQQLAGKRIGVFSYGSGLAATLYSLKVTQDATPGSALDKIT
	ASLCDLKSRLDSRTGVAPDVFAENMKLREDTHHLVNYIPQGSIDSLFEGTWYLVRVDEKHRRTYARR
	PTPNDDTLDEGVGLVHSNIATEHIPSPAKKVPRLPATAAEPEAAVISNGEH
	SEQ ID NO: 191	1601 bp
NOV41f,	CACCGGTCTCACATGCCTGGATCACTTCCTTTGAATGCAGAAGCTTGCTGGCCAAAAGATGTGGGAA
253174237 DNA
Sequence	TTGTTGCCCTTGAGATCTATTTTCCTTCTCAATATGTTGATCAAGCAGAGTTGGAAAAATATGATGG
	TGTAGATGCTGGAAAATATACCATTGGCTTGGGCCAGGCCAAGATGGGCTTCTGCACAGATAGAGAA
	GATATTAACTCTCTTTGCATGACTGTGGTTCAGAATCTTATGGAGAGAAATAACCTTTCCTATGATT
	GCATTGGGCGGCTGGAAGTTGGAACAGAGACAATCATCGACAAATCAAAGTCTGTGAAGACTAATTT
	GATGCAGCTGTTTGAAGAGTCTGGGAATACAGATATAGAAGGAATCGACACAACTAATGCATGCTAT
	GGAGGCACAGCTGCTGTCTTCAATGCTGTTAACTGGATTGAGTCCAGCTCTTGGGATGGACGGTATG
	CCCTGGTAGTTGCAGGAGATATTGCTGTATATGCCACAGGAAATGCTAGACCTACAGGTGGAGTTGG
	AGCAGTAGCTCTGCTAATTGGGCCAAATGCTCCTTTAATTTTTGAACGAGGGCTTCGTGGGACACAT
	ATGCAACATGCCTATGATTTTTACAAGCCTGATATGCTATCTGAATATCCTATAGTAGATGGAAAAC
	TCTCCATACAGTCCTACCTCAGTGCATTAGACCGCTGCTACTCTGTCTACTGCAAAAAGATCCATGC
	CCAGTGGCAGAAAGAGGGAAATGATAAAGATTTTACCTTGAATGATTTTGGCTTCATGATCTTTCAC
	TCACCATATTGTAAACTGGTTCAGAAATCTCTAGCTCGGATGTTGCTGAATGACTTCCTTAATGACC
	AGAATAGAGATAAAAATAGTATCTATAGTGGCCTGGAAGCCTTTGGGGATGTTAAATTAGAAGACAC
	CTACTTTGATAGAGATGTGGAGAACGCATTTATGAAGGCTAGCTCTGAACTCTTCAGTCAGAAAACA
	AAGGCATCTTTACTTGTATCAAATCAAAATGGAAATATGTACACATCTTCAGTATATGGTTCCCTTG
	CATCTGTTCTAGCACAGTACTCACCTCAGCAATTAGCAGGGAAGAGAATTCGAGTGTTTTCTTATGG
	TTCTGGTTTGGCTGCCACTCTGTACTCTCTTAAAGTCACACAAGATGCTACACCGGGGTCTCCTCTT
	GATAAAATAACAGCAAGTTTATGTGATCTTAAATCAAGGCTTGATTCAAGAACTGGTGTGGCACCAG
	ATGTCTTCGCTGAAAACATGAAGCTCAGAGAGGACACCCATCATTTGGTCAACTATATTCCCCAGGG
	TTCAATAGATTCACTCTTTGAAGGAACGTGGTACTTAGTTAGGGTGGATGAAAAGCACAGAAGAACT
	TACGCTCGGCGTCCCACTCCAAATGATGACACTTTGGATGAAGGAGTAGGACTTGTGCATTCAAACA
	TAGCAACTGAGCATATTCCAAGCCCTGCCAAGAAAGTACCAAGACTCCCTGCCACAGCAGCAGAACC
	TGAAGCAGCTGTCATTAGTAATGGGGAACATCATCACCACCATCACTAAGCGCCCGCAAG
	ORF Start: at 1		ORF Stop: TAA at 1588
	SEQ ID NO: 192	529 aa	MW at 58496.2kD
NOV41f,	HRSHMPGSLPLNAEACWPKDVGIVALETYFPSQYVDQAELEKYDGVDAGKYTIGLGQAKMGFCTDRE
253174237
Protein	DINSLCMTVVQNLMERNNLSYDCIGRLEVGTETIIDKSKSVKTNLMQLFEESGNTDIEGIDTTNACY
Sequence
	CGTAAVFNAVNWIESSSWDGRYALVVAGDIAVYATGNARPTGGVGAVALLIGPNAPLIFERGLRGTH
	MQHAYDFYKPDMLSEYPIVDGKLSIQCYLSALDRCYSVYCKKIHAQWQKECNDKDFTLNDFGFMIFH
	SPYCKLVQKSLARMLLNDFLNDQNRDKNSIYSGLEAFGDVKLEDTYFDRDVEKAFMKASSELFSQKT
	KASLLVSNQNGNMYTSSVYGSLASVLAQYSPQQLAGKRIGVFSYGSGLAATLYSLKVTQDATPGSAL
	DKITASLCDLKSRLDSRTGVAPDVFAENHKLREDTHHLVNYIPQGSIDSLFEGTWYLVRVDEKHRRT
	YARRPTPNDDTLDEGVGLVHSNIATEHIPSPAKKVPRLPATAAEPEAAVISNGEHHHHHH
	SEQ ID NO: 193	1650 bp
NOV41g,	CCTTCACACAGCTCTTTCACCATGCCTGGATCACTTCCTTTGAATGCAGAAGCTTGTGCCAAAAG
CG97025-01
DNA Sequence	ATGTTGGGATTGTTGCCCTTGAGATCTATTTTCCTTCTCAATATGTTGATCAAGCAGAGTTGGAAAA
	ATATGATGGTGTAGATGCTGGGAAGTATACCATTGGCTTGGGCCAGGCCAAGATGGGCTTCTGCACA
	GATAGAGAAGATATTAACTCTCTTTGCATGACTGTGGTTCAGAATCTTATGGAGAGAAATAACCTTT
	CCTATGATTGCATTGGGCGGCTGGAAGTTGGAACAGAGACAATCATCGACAAATCAAAGTCTGTGAA
	GACTAATTTGATGCAGCTGTTIGAAGAGTCTGGGAATACAGATATAGAAGGAATCGACACAACTAAT
	GCATGCTATGGAGGCACAGCTGCTGTCTTCAATGCTGTTAACTGGATTGAGTCCAGCTCTTGGGATG
	GACGGTATGCCCTGGTAGTTGCAGGAGATATTGCTGTATATGCCACAGGAAATGCTAGACCTACAGG
	TGGAGTTGGAGCAGTAGCTCTGCTAATTGGGCCAAATGCTCCTTTAATTTTTGAACGAGGGCTTCGT
	GGGACACATATGCAACATGCCTATGATTTTTACAAGCCTGATATGCTATCTGAATATCCTATAGTAG
	ATGGGAAACTCTCCATACAGTGCTACCTCAGTGCATTAGACCGCTGCTATTCTGTCTACTGCAAAAA
	GATCCATGCCCAGTGGCAGAAAGAGGGAAATGATAAAGATTTTACCTTGAATGATTTTGGCTTCATG
	ATCTTTCACTCACCATATTGTAAACTCGTTCAGAAATCTCTAGCTCGGATGTTGCTGAATGACTTCC
	TTAATGACCAGAATAGAGATAAAAATAGTATCTATAGTGGCCTGGAAGCCTTTGGGGATGTTAAATT
	AGAAGACACCTACTTTGATAGAGATGTGGAGAAGGCATTTATGAAGGCTAGCTCTGAACTCTTCAGT
	CAGAAAACAAAGGCATCTTTACTTGTATCAAATCAAAATGGAAATATGTACACATCTTCAGTATATG
	GTTCCCTTGCATCTGTTCTAGCACAGTACTCACCTCAGCAATTAGCAGGGAAGAGAATTGGAGTGTT
	TTCTTATGGTTCTGGTTTGGCTGCCACTCTGTACTCTCTTAAAGTCACACAAGATGCTACACCGGGG
	TCTGCTCTTGATAAAATAACAGCAAGTTTATGTGATCTTAAATCAAGGCTTGATTCAAGAACTGGTG
	TGGCACCAGATGTCTTCGCTGAAAACATGAAGCTCAGAGAGGACACCCATCATTTGGTCAACTATAT
	TCCCCAGGGTTCAATAGATTCACTCTTTGAAGGAACGTGGTACTTAGTTAGGGTGGATGAAAAGCAC
	AGAAGAACTTACCCTCGGCGTCCCACTCCAAATGATGACACTTTGGATGAAGGAGTAGGACTTGTGC
	ATTCAAACATAGCAACTGAGCATATTCCAAGCCCTGCCAAGAAAGTACCAAGACTCCCTGCCACAGC
	AGCAGAACCTGAAGCAGCTGTCATTAGTAATGGGGAACATTAAGATACTCTGTGAGGTGCAAGACTT
	CAGGGTGGGGTGGGCATGGGGTGGGGGTATGGGAACAGTTCG
	ORF Start: ATG at 22		ORF Stop: TAA at 1582
	SEQ ID NO: 194	520 aa	MW at 57293.0kD
NOV41g,	MPGSLPLNAEACWPKDVGIVALEIYFPSQYVDQAELEKYDGVDAGKYTIGLGQAKMGFCTDREDINS
CG97025-01
Protein Sequence	LCMTVVQNLMERNNLSYDCIGRLEVGTETIIDKSKSVKTNLMQLFEESGNTDIEGIDTTNACYGGTA
	AVFNAVNWIESSSWDGRYALVVAGDIAVYATGNARPTGGVGAVALLIGPNAPLIFERGLRCTHMQHA
	YDFYKPDMLSEYPIVDGKLSIQCYLSALDRCYSVYCKKIHAQWQKEGNDKDFTLNDFGFMIFHSPYC
	KLVQKSLARMLLNDFLNDQNRDKNSIYSGLEAFGDVKLEDTYFDRDVEKAFHKASSELFSQKTKASL
	LVSNQMGNMYTSSVYGSLASVLAQYSPQQLAGKRIGVFSYGSGLAATLYSLKVTQDATPGSALDKIT
	ASLCDLKSRLDSRTGVAPDVFAENHKLREDTHHLVNYIPQGSIDSLFEGTWYLTRVDEKHRRTYARR
	PTPNDDTLDEGVGLVHSNIATEHI PSPAKKVPRLPATAAEPEAAVISNGEH
	SEQ ID NO: 195	1608 bp
NOV41h,	CCTCGATCACTTCCTTTGAATGCAGAAGCTTGCTGGCCAAAAGATGTGGGAATTGTTGCCCTTGAGA
256420363 DNA
Sequence	TCTATTTTCCTTCTCAATATGTTGATCAAGCAGAGTTGGAAAAATATGATGGTGTAGATGCTGGAAA
	GTATACCATTGGCTTGGGCCAGGCCAAGATGGCCTTCTGCACAGATAGAGAAGATATTAACTCTCTT
	TGCATGACTGTGGTTCAGAATCTTATGGAGAGAAATAACCTTTCCTATGATTGCATTGGGCGGCTGG
	AAGTTGGAACAGAGACAATCATCGACAAATCAAAGTCTGTGAAGACTAATTTGATGCAGCTGTTTGA
	AGAGTCTCGGAATACAGATATAGAAGGAATCGACACAACTAATGCATGCTATGGAGGCACAGCTGCT
	GTCTTCAATGCTGTTAACTGGATTGAGTCCAGCTCTTGGGATGGACGGTATCCCCTGGTAGTTGCAG
	GAGATATTGCTGTATATGCCACAGCAAATGCTAGACCTACAGGTGGAGTTGGAGCAGTAGCTCTGCT
	AATTGGGCCAAATGCTCCTTTAATTTTTGAACGAGGGCTTCGTGGGACACATATGCAACATGCCTAT
	GATTTTTACAAGCCTGATATGCTATCTGAATATCCTATAGTAGATGGAAAACTCTCCATACAGTGCT
	ACCTCAGTGCATTAGACCGCTGCTACTCTGTCTACTGCAAAAAGATCCATGCCCAGTGGCAGAAAGA
	GGGAAATGATAAAGATTTTACCTTGAATGATTTTGGCTTCATGATCTTTCACTCACCATATTGTAAA
	CTGGTTCAGAAATCTCTAGCTCGGATGTTGCTGAATGACTTCCTTAATGACCAGAATAGAGATAAAA
	ATAGTATCTATAGTGGCCTGGAAGCCTTTCGGGATGTTAAATTAGAAGACACCTACTTTGATAGAGA
	TGTGGAGAAGGCATTTATGAAGGCTAGCTCTGAACTCTTCAGTCAGAAAACAAAGGCATCTTTACTT
	GTATCAAATCAAAATCGAAATATGTACACATCTTCAGTATATGGTTCCCTTCCATCTGTTCTAGCAC
	AGTACTCACCTCAGCAATTAGCAGGGAAGAGAATTGGAGTGTTTTCTTATGGTTCTGGTTTGGCTGC
	CACTCTGTACTCTCTTAAAGTCACACAAGATGCTACACCGGGGTCTGCTCTTGATAAAATAACAGCA
	AGTTTATGTGATCTTAAATCAAGGCTTGATTCAAGAACTGGTGTGGCACCAGATGTCTTCGCTGAAT
	ACATGAAGCTCAGAGAGGACACCCATCATTTGGTCAACTATATTCCCCAGGGTTCAATAGATTCACT
	CTTTGAAGGAACGTGGTACTTAGTTAGGGTGGATGAAAAGCACAGAAGAACTTACGCTCGGCGTCCC
	ACTCCAAATGATGACACTTTGGATGAAGGAGTAGGACTTGTCCATTCAAACATAGCAACTGAGCATA
	TTCCAAGCCCTGCCAAGAAAGTACCAAGACTCCCTGCCACAGCAGCAGAACCTGAAGCAGCTGTCAT
	TAGTAATGGGGAACATCATCACCACCATCACTAAGCGGCCGCACTCGAGCACCACCACCACCACCAC
	ORF Start: at 1		ORF Stop: TAA at 1573
	SEQ ID NO: 196	524 aa	MW at 57847.5kD
NOV41h,	PGSLPLNAEACWPKDVGIVALEIYFPSQYVDQAELEKYDGVDAGKYTIGLGQAKMGFCTDREDINSL
256420363
Protein Sequence	CMTVVQNLMERNNLSYDCIGRLEVGTETIIDKSKSVKTNLMQLFEESGNTDIEGIDTTNACYGGTAA
	VFNAVNWIESSSWDGRYALVVAGDIAVYATGNARPTGGVGAVALLIGPNAPLIFERGLRGTHMQHAY
	DFYKPDMLSEYPIVDGKLSIQCYLSALDRCYSVYCKKIHAQWQKEGNKKDFTLNDFGFMIFHSPYCK
	LVQKSLARMLLNDFLNDQNRDKNSIYSGLEAFGDVKLEDTYFDRDVEKAFMXASSELFSQKTKASLL
	VSNQNGNMYTSSVYGSLASVLAQYSPQQLAGKRIGVFSYGSGLAATLYSLKVTQDATPGSALDKITA
	SLCDLKSRLDSRTGVAPDVFAENHKLREDTHHLVNYIPQGSDSLFEGTWYLVRXTDEKHRRTYARRP
	TPNDDTLDEGVGLVHSNIATEHIPSPAKKVPRLPATAAEPEAAVISNGEHHHHGH
	SEQ ID NO: 197	1650 bp
NOV41j,	CCTTCACACAGCTCTTTCACCATGCCTGGATCACTTCCTTTGAATGCAGAAGCTTGCTGGCCAAAAG
CG97025-01
DNA Sequence	ATGTTGGGATTGTTGCCCTTGAGATCTATTTTCCTTCTCAATATGTTGATCAAGCAGAGTTGGAAAA
	ATATGATGGTGTAGATGCTGGGAAGTATACCATTGGCTTGGGCCAGGCCAAGATGGGCTTCTGCACA
	GATAGAGAAGATATTAACTCTCTTTGCATGACTGTGGTTCAGAATCTTATGGAGAGAAATAACCTTT
	CCTATGATTGCATTGGGCGGCTGCAAGTTGGAACAGAGACAATCATCGACAAATCAAAGTCTCTGAA
	GACTAATTTGATGCAGCTGTTTGAAGAGTCTGCGAATACAGATATAGAAGGAATCGACACAACTAAT
	GCATGCTATGGAGGCACAGCTGCTGTCTTCAATGCTGTTAACTGGATTGAGTCCAGCTCTTGGGATG
	GACGGTATGCCCTGGTAGTTGCAGGAGATATTGCTGTATATGCCACAGGAAATGCTAGACCTACAGG
	TGGAGTTGGAGCACTAGCTCTCCTAATTGGGCCAAATGCTCCTTTAATTTTTGAACGAGGGCTTCGT
	GGGACACATATGCAACATGCCTATGATTTTTACAAGCCTGATATGCTATCTGAATATCCTATAGTAG
	ATGGGAAACTCTCCATACAGTGCTACCTCAGTGCATTAGACCGCTGCTATTCTGTCTACTGCAAAAA
	GATCCATGCCCAGTGGCAGAAAGAGGGAAATGATAAGATTTTACCTTGAATCAATTTTGGCTTCATG
	ATCTTTCACTCACCATATTGTAAACTGGTTCAGAAATCTCTAGCTCCGATGTTGCTGAATGACTTCC
	TTAATGACCAGAATAGAGATAAAAATAGTATCTATAGTGGCCTGGAAGCCTTTGGGGATGTTAAATT
	AGAAGACACCTACTTTGATAGAGATGTGGAGAAGGCATTTATGAAGGCTAGCTCTGAACTCTTCAGT
	CAGAAAACAAAGGCATCTTTACTTGTATCAAATCAATAATGGAAATTGTACACATCTTCAGTATATG
	GTTCCCTTGCATCTGTTCTAGCACAGTACTCACCTCAGCAATTAGCAGGGAAGAGAATTGGAGTGTT
	TTCTTATGGTTCTGGTTTGGCTGCCACTCTGTACTCTCTTAAAGTCACACAAGATGCTACACCTAGG
	TCTGCTCTTGATAAAATAACAGCAAGTTTATGTGATCTTAAATCAAGGCTTGATTCAAGAACTGGTG
	TGGCACCAGATGTCTTCGCTGAAAACATGAAGCTCAGAGAGGACACCCATCATTTGGTCAACTATAT
	TCCCCAGGGTTCAATAGATTCACTCTTTGAAGGAACGTGGTACTTAGTTAGGGTGGATGAAAAGCAC
	AGAAGAACTTACGCTCGGCGTCCCACTCCAAATGATGACACTTTGGATGAAGGAGTAGGACTTGTGC
	ATTCAAACATAGCAACTGAGCATATTCCAAGCCCTGCCAAGAAAGTACCAAGACTCCCTGCCACAGC
	AGCAGACCTGAAGCAGCTGTCATTAGTAATGGGGAACATTAAGATACTCTGGTGACGTCCAAGACTT
	CAGGGTGGGGTGGGCATGGGGTGGGGGTATGGGAACAGTTGG
	ORF Start: ATG at 22		ORF Stop: TAA at 1582
	SEQ ID NO: 198	520aa	MW at 57293.0kD
NOV41i,	MPGSLPLNAEACWPKDVGIVALEIYFPSQYVDQAELEKYDGVDAGKYTIGLGQAXMGFCTDREDINS
CG97025-01
Protein	LCNTVVQNLMERNNLSYDCIGRLEVGTETIIDKSKSVKTNLMQLFEESGNTDIEGIDTTNACYCGTA
Sequence
	AVFNAWIEWSSSWDGRYALVVAGDIAVYATGNARPTGGVGAVALLIGPNAPLIFERGTLRGTHMQHA
	YDFYKPDNLSEYPTVDGKLSTQCYLSALDRCYSVYCKKIHAQWQKEGNDKDFTLNDFGFMIFHSPYC
	KLVQKSLARMLLNDFLNDQNRDKNSIYSGLEAFGDVKLEDTYFDRDVEKAFMKASSELFSQKTKASL
	LVSNQNGNMYTSSVYGSLASVLAWYSPQQLAGKRIGVFSYGSGLAATLYSLKVTQDATPGSALDKIT
	LVSNQNGNMYTSSVYGSLASVLAQYSPQQLAGKRIGVFSYGSGLAATLYSLKVTQDATPGSALDKIT
	ASLCDLKSRLDSRTGVAPDVFAENMKLREDTHHLVNYIPQGSIDSLFEGTWYLVRVDEKHRRTYARR
	PTPNDDTLDEGVGLVHSNIATEHIPSPAKKVPRLPATAAEPEAAVISNGEH
	SEQ ID NO: 199	1612 bp
NOV41j,	ACATCATCACCACCATCACCCTGGATCACTTCCTTTGAATGCAGAAGCTTGCTGGCCAAAAGATGTG
255667064 DNA
Sequence	GGAATTGTTGCCCTTGAGATCTATTTTCCTTCTCAATATGTTGATCAAGCAGAGTTGGAAAAATATG
	ATGGTGTAGATGCTGGAAAGTATACCATTGGCTTGGGCCAGGCCAAGATGGGCTTCTGCACAGATAG
	AGAAGATATTAACTCTCTTTGCATGACTGTGGTTCAGAATCTTATGGAGAGAAATAACCTTTCCTAT
	GATTGCATTGGGCGGCTGGAAGTTGGAACAGAGACAATCATCGACAAATCAAAGTCTGTGAAGACTA
	ATTTGATGCAGCTGTTTGAAGAGTCTGGGAATACAGATATAGAAGGAATCGACACAACTAATGCATG
	CTATGGAGGCACAGCTGCTGTCTTCAATGCTGTTAACTGGATTGAGTCCAGCTCTTGGGATGOACGG
	TATGCCCTGGTAGTTGCAGGAGATATTGCTGTATATGCCACAGGAAATGCTAGACCTACAGGTGGAG
	TTGGAGCAGTAGCTCTGCTAATTGGGCCAAATGCTCCTTTAATTTTTGAACGACGGCTTCGTGGGAC
	ACATATGCAACATGCCTATGATTTTTACAAGCCTGATATGCTATCTGAATATCCTATAGTAGATGGA
	AAACTCTCCATACAGTGCTACCTCAGTGCATTAGACCGCTGCTACTCTGTCTACTGCAAAAAGATCC
	ATGCCCAGTGGCAGAAAGAGGGAAATGATAAAGATTTTACCTTGAATGATTTTGGCTTCATGATCTT
	TCACTCACCATATTGTAAACTGGTTCAGAAATCTCTAGCTCGGATGTTGCTGAATGACTTCCTTAAT
	GACCAGAATAGAGATAAAAATAGTATCTATAGTGGCCTGGAAGCCTTTGGGGATGTTAAATTAGAAG
	ACACCTACTTTGATAGAGATGTGGAGAAGGCATTTATCAAGGCTAGCTCTGAACTCTTCAGTCAGAA
	AACAAAGGCATCTTTACTTGTATCAAATCAAAATGGAAATATGTACACATCTTCAGTATATGGTTCC
	CTTGCATCTGTTCTAGCACAGTACTCACCTCAGCAATTAGCAGGGAAGAGAATTGGAGTGTTTTCTT
	ATGGTTCTGGTTTGGCTGCCACTCTGTACTCTCTTAAAGTCACACAAGATGCTACACCGGGGTCTGC
	TCTTGATAAAATAACAGCAAGTTTATGTGATCTTAAATCAAGGCTTGATTCAAGAACTGGTGTGGCA
	CCAGATGTCTTCGCTGAAAACATGAAGCTCAGAGAGGACACCCATCATTTGGTCAACTATATTCCCC
	AGGGTTCAATAGATTCACTCTTTGAAGGAACGTGGTACTTAGTTAGGGTGGATGAAAAGCACAGAAG
	AACTTACGCTCGGCGTCCCACTCCAAATGATGACACTTTGGATGAAGGAGTAGGACTTGTGCATTCA
	AACATAGCAACTGAGCATATTCCAAGCCCTGCCAAGAAAGTACCAAGACTCCCTGCCACAGCAGCAG
	AACCTGAGCAGCTGTCATTAGTAATGGGGAACATTAAGCGGCCGCACTCGAGCACCACCACCACCA
	CCAC
	ORF Start: at 2		ORF Stop: TAA at 1577
	SEQ ID NO: 200	525 aa	MW at 57984.6kD
NOV41j,	HHHHHHPGSLPLNAEACWPKDVGIVALEIYFPSQYVDQAELEKYDGVDAGKYTIGLCQAXMGFCTDR
255667064
Protein	EDINSLCMTVVQNLMERNNLSYDCIGRLEVGTETIIDKSKSVKTNLMQLFEESGNTDIEGIDTTNAC
Sequence
	YGGTAAVFNAVNWIESSSWDGRYALVVAGDIAVYATGNARPTGGVGAVALLIGPNAPLIFERGLRGT
	HMQHAYDFYKPDMLSEYPIVDGKLSIQCYLSALDRCYSVYCKKIHAQWQKEGNDKDFTLNDFGFMIF
	HSPYCKLVQKSLARMLLNDFLNDQNRDKNSIYSGLEAFGDVKLEDTYFDRDVEKAFMKASSELFSQK
	TKASLLVSNQNGNMYTSSVYGSLASVLAQYSPQQLAGKRIGVFSYGSGLAATLYSLKVTQDATFGSA
	LDKITASLCDLKSRLDSRTGVAPDVFAENMKLREDTHHLVNYIPQGSIDSLFEGTWYLVRVDEKHRR
	TYARRPTPNDDTLDEGVGLVHSNIATEHIPSPAKKVPRLPATAAEPEAAVISNGEH
	SEQ ID NO: 201	1650 bp
NOV41k,	CCTTCACACAGCTCTTTCACCATGCCTGGATCACTTCCTTTGAATGCAGAAGCTTGCTGGCCAAAAG
CG97025-01
DNA Sequence	ATGTTGGGATTGTTGCCCTTGAGATCTATTTTCCTTCTCAATATGTTGATCAAGCAGAGTTGGAAAA
	ATATGATGGTGTAGATGCTGGGAAGTATACCATTGGCTTGGGCCAGGCCAAGATGGGCTTCTGCACA
	GATAGAGAAGATATTAACTCTCTTTGCATGACTGTGGTTCAGAATCTTATGGAGAGAAATAACCTTT
	CCTATGATTGCATTGGGCGGCTGGAAGTTGGAACAGAGACAATCATCGACAAATCAATGTCTGTGAA
	GACTAATTTGATGCAGCTGTTTGAAGAGTCTGGGAATACAGATATAGAAGGATCGACACAACTAAGT
	GCATGCTATGGAGGCACAGCTGCTGTCTTCAATGCTGTTAACTGGATTGAGTCCAGCTCTTGGGATG
	GACGGTATGCCCTGGTAGTTGCAGGAGATATTGCTGTATATGCCACAGGAAATGCTAGACCTACAGC
	TGGAGTTGGAGCAGTAGCTCTGCTAATTGGGCCAAATGCTCCTTTAATTTTTGAACGAGGGCTTCGT
	GGGACACATATGCAACATGCCTATGATTTTTACAAGCCTGATATGCTATCTGAATATCCTATAGTAG
	ATGGGAAACTCTCCATACAGTGCTACCTCAGTGCATTAGACCGCTGCTATTCTGTCTACTGCAAAAA
	GATCCATGCCCAGTGGCAGAAAGAGGGAAATGATAAAGATTTTACCTTGAATGATTTTGGCTTCATG
	ATCTTTCACTCACCATATTGTAAACTGGTTCAGAAATCTCTAGCTCGGATGTTGCTGAATGACTTCC
	TTAATGACCAGAATAGAGATAAAAATAGTATCTATAGTGGCCTGGAAGCCTTTGGGGATGTTAAATT
	AGAAGACACCTACTTTGATAGAGATGTGGAGAAGGCATTTATGAAGGCTAGCTCTGAACTCTTCAGT
	CAGAAAACAAAGGCATCTTTACTTGTATCAAATCAAAATGGAAATATGTACACATCTTCAGTATATG
	GTTCCCTTGCATCTGTTCTAGCACACTACTCACCTCAGCAATTAGCAGGGAAGAGAATTGGAGTGTT
	TTCTTATGGTTCTGGTTTGGCTGCCACTCTGTACTCTCTTAAAGTCACACAAGATGCTACACCGGGG
	TCTGCTCTTGATAAAATAACAGCAAGTTTATGTGATCTTAAATCAAGGCTTGATTCAAGAACTGGTG
	TGGCACCAGATGTCTTCGCTGAAAACATGAAGCTCAGAGAGGACACCCATCATTTGGTCAACTATAT
	TCCCCAGCGTTCAATAGATTCACTCTTTGAAGGAACGTGGTACTTAGTTAGGGTGGATGAAAAGCAC
	AGAAGAACTTACGCTCGGCGTCCCACTCCAAATGATCACACTTTGGATGAAGGAGTAGGACTTGTGC
	ATTCAAACATAGCAACTGAGCATATTCCAAGCCCTGCCAAGAAAGTACCAAGACTCCCTGCCACAGC
	AGCAGAACCTGAAGCAGCTGTCATTAGTAATGGGGAACATTAAGATACTCTGTGAGGTGCAAGACTT
	CAGCGTGGGGTGGGCATGGGGTGGGGGTATGGGAACAGTTGG
	ORF Start: ATG at 22		ORF Stop: TAA at 1582
	SEQ ID NO: 202	520 aa	MW at 57293.0kD
NOV41k,	MPGSLPLNAFiACWPKDVGIVALEIYFPSQYVDQAELEKYDGVDAGKYTIGLGQAKMGFCTDREDINS
CG97025-01
Protein Sequence	LCMTVVQNLMERNNLSYDCIGRLEVGTETIIDKSKSVKTNLMSQLFEESGNTDIEGIDTTNACYGGTA
	AVFNAVNWIESSSWDGRYALVVAGDIAVYATGNARPTGGVGAVALLIGPNAPLIFERGLRGTNNMQHA
	YDFYKPDMLSEYPIVDGGKLSIQCYLSALDRCYSVYCKKIHAQWQKEGNFKDFTLNDFGFMIFHSPYC
	KLVQKSLARMLLNDFLNDQNRDKNSIYSGLEAFGDVKLEDTYFDRDVEKAFMKASSELFSGQKTKASL
	LVSNQNGNMYTSSVYGSLASVLAQYSPQQLAGKRIGVFSYGSGLAATLYSLKVTQDATPKGSALDKIT
	ASLCDLKSRLDSRTGVAPDVFAENMHREDTHHLVNYIPQGSIDSLFEGTWYLVRVDEGKKHRRTYARR
	PTPNDDTLDEGVGLVHSNVTATEHIPSPAKKVPRLPATAAEPEAAVISNGEH
	SEQ ID NO: 203	1564 bp
NOV41L,	CATGCCTGGATCACTTCCTTTGAATGCAGAAGCTTGCTGGCCAAAAGATGTGGGAATTGTTGCCCTT
228832739 DNA
Sequence	GAGATCTATTTTCCTTCTCAATATGTTGATCAAGCAGAGTTGGAAAAATATGATGGTGTAGATGCTG
	GAAAGTATACCATTGGCTTGGGCCAGGCCAAGATGGGCTTCTGCACAGATAGAGAAGATATTAACTC
	TCTTTGCATGACTGTGGTTCAGAATCTTATGGAGAGAAATAACCTTTCCTATGATTGCATTGGGCGG
	CTGGAAGTTGCAACAGAGACAATCATCGACAAATCAAAGTCTGTGAAGACTAATTTGATGCAGCTGT
	TTGAAGAGTCTGGGAATACAGATATAGAAGGAATCGACACAACTAATGCATGCTATGGACGCACAGC
	TGCTGTCTTCAATGCTGTTAACTGGATTGAGTCCAGCTCTTGGGATGGACGGTATGCCCTGGTAGTT
	GCAGGAGATATTGCTGTATATGCCACAOGAAATGCTAGACCTACAGGTGGAGTTGGAGCAGTAGCTC
	TGCTAATTGGGCCAAATGCTCCTTTAATTTTTGAACGAGGGCTTCGTGGGACACATATGCAACATGC
	CTATGATTTTTACAAGCCTGATATGCTATCTGAATATCCTATAGTAGATGGAAAACTCTCCATACAG
	TGCTACCTCAGTGCATTAGACCGCTGCTACTCTGTCTACTGCAAAAAGATCCATGCCCAGTGGCAGA
	AAGAGGGAAATGATAAAGATTTTACCTTGAATGATTTTGGCTTCATGATCTTTCACTCACCATATTG
	TAAACTGGTTCAGAAATCTCTAGCTCGGATGTTGCTGAATGACTTCCTTAATGACCAGAATAGAGAT
	AAAAATAGTATCTATAGTGGCCTGGAAGCCTTTGGGGATGTTAAATTAGAAGACACCTACTTTGATA
	GAGATGTGGAGAAGGCATTTATGAAGGCTAGCTCTGAACTCTTCAGTCAGAAAACAAAGGCATCTTT
	ACTTGTATCAAATCAAAATGGAAATATGTACACATCTTCAGTATATGGTTCCCTTGCATCTGTTCTA
	GCACAGTACTCACCTCAGCAATTAGCAGGGAAGAGAATTGGAGTGTTTTCTTATGGTTCTGGTTTGG
	CTGCCACTCTGTACTCTCTTAAAGTCACACAAGATGCTACACCGGGGTCTGCTCTTGATAAAATAAC
	AGCAAGTTTATGTGATCTTAAATCAAGGCTTGATTCAAGAACTGGTGTGGCACCAGATGTCTTCGCT
	GAAAACATGAAGCTCAGAGAGGACACCCATCATTTGGTCAACTATATTCCCCAGGGTTCAATAGATT
	CACTCTTTGAAOGAACGTGGTACTTAGTTAGGGTGGATGAAAAGCACAGAAGAACTTACGCTCGGCG
	TCCCACTCCAAATGATGACACTTTGGATGAAGGAGTAGGACTTGTGCATTCAAACATAGCAACTGAG
	CATATTCCAAGCCCTGCCAAGAAAGTACCAAGACTCCCTGCCACAGCAGCAGAACCTGAAGCAGCTG
	TCATTAGTAATGGGGAACATTAA
	ORF Start: ATG at 2		ORF Stop: TAA at 1562
	SEQ ID NO: 204	520 aa	MW at 57293.0kD
NOV41l,	NPGSLPLNAEACWPKDVGIVALEIYFPSQYVDQAELEKYDGVDAGKYTIGLGQAKMGFCTDREDINS
228832739
Protein	LCMTVVQNLMERTTHTHSYDCIGRLEVGTETDKSKSVKTNLMQLFEESGNTDIEGIDTTNACYGGTA
Sequence
	AVFNAVNWIESSSWDGRYALVVAGDIAVYATGNARPTGGVGAVALLIGPNAPLIFERGLRGTHMQHA
	YDFYKPDMLSEYPIVDGKLSIQCYLSALDRCYSVYCKKIHAQWQKEGNDKDFTLNDFGFMIFHSPYC
	KLVQKSLARMLLNDFLNDQNRDKNSIYSGLEAFGDVKLEDTYFDRDVEKAFMXASSELFSQKTKASL
	ASLCDLKSRLDSRTGVAPDVFAENNKLREDTHHLVNYIPQGSIDSLFEGTWYLVRVDEKHRRTYARR
	PTPNDDTLDEGVGLVHSNIATEHIPSPAKKVPRLPATAAEPEAAVISNGEH
	SEQ ID NO: 205	1650 bp
NOV41m,	+E,unc CCTTCACACAGCTCTTTCACCATGCCTGGATCACTTCCTTTGAATGCAGAAGCTTGCTGGCCAAAA
CG97025-02
DNA Sequence	AAATATGATGGTGTAGATGCTGGGAAGTATACCATTGGCTTGGGCCAGGCCAAGATGGGCTTCTGC
	ACAGATAGAGAAGATATTAACTCTCTTTGCATGACTGTGGTTCAGAATCTTATGGAGAGAAATAAC
	CTTTCCTATGATTGCATTGGGCGGCTGGAAOTTGGAACAGAGACAATCATCGACAAATCAAAGTCT
	GTGAAGACTAATTTGATGCAGCTGTTTGAAGAGTCTCGGAATACAGATATAGAAGGAATCGACACA
	ACTAATGCATGCTATGGAGGCACAGCTGCTGTCTTCAATGCTGTTAACTGGATTGAGTCCAGCTCT
	TGGCATGGACGGTATGCCCTGGTAGTTGCAGGAGATATTGCTGTATATGCCACAGGAAATGCTAGA
	CCTACAGGTGGAGTTGGAGCAGTAGCTCTGCTAATTGGGCCAAATGCTCCTTTAATTTTTGAACGA
	GGGCTTCGTGGGACACATATGCAACATCCCTATGATTTTTACAAGCCTGATATGCTATCTGAATAT
	CCTATAGTAGATGGGAAACTCTCCATACACTGCTACCTCAGTGCATTAGACCGCTGCTATTCTGTC
	TACTGCAAAAAGATCCATGCCCAGTGGCAGAAAGAGGGAAATGATAAAGATTTTACCTTGAATGAT
	TTTGGCTTCATGATCTTTCACTCACCATATTGTAAACTGGTTCAGAAATCTCTAGCTCGGATGTTG
	CTGAATGACTTCCTTAATGACCAGAATAGAGATAAAAATAGTATCTATAGTGGCCTGGAAGCCTTT
	GGGGATGTTAAATTAGAAGACACCTACTTTGATAGAGATTTCGAGAAGGCATTTATGAAGOCTAGC
	TCTGAACTCTTCAGTCAGAAAACAAAGGCATCTTTACTTGTATCAAATCAAAATGGAAATATGTAC
	ACATCTTCAGTATATGGTTCCCTTGCATCTGTTCTAGCACAGTACTCACCTCAGCAATTAGCAGGG
	AAGAGAATTGGAGTGTTTTCTTATGGTTCTGGTTTGGCTGCCACTCTGTACTCTCTTAAAGTCACA
	CAAGATGCTACACCGGGGTCTGCTCTTGATAAAATAACAGCAAGTTTATGTGATCTTAAATCAAGG
	CTTGATTCAAGAACTGGTGTGGCACCAGATGTCTTCGCTGAAAACATGAAGCTCAGAGACGACACC
	CATCATTTGGTCAACTATATTCCCCAGGGTTCAATAGATTCACTCTTTGAAGGAACGTGGTACTTA
	GTTAGGGTGGATGAAAAGCACAGAAGAACTTACGCTCGGCGTCCCACTCCAAATGATGACACTTTG
	GATGAAGGAGTAGGACTTGTGCATTCAAACATAGCAACTGAGCATATTCCAAGCCCTGCCAAGAAA
	GTACCAAGACTCCCTGCCACAGCAGCAGAACCTGAAGCAGCTGTCATTAGTAATGGGGAACATTAA
	GATACTCTGTGAGGTGCAAGACTTCAGGGTGGGGTGGGCATGGGGTGGGGGTATGGGAACAGTTGG
	ORF Start: ATG at 22		ORF Stop: TAA at 1582
	SEQ ID NO: 206	520 aa	MW at 57293.0kD
NOV41m,	MPGSLPLNAEACWPKDVGIVALEIYFPSQYVDQAELEKYDGVDAGKYTIGLGQAXMGFCTDREDIN
CG97025-02
Protein Sequence	SLCMTVVQNLMERNNLSYDCIGRLEVGTETIIDKSKSVKTNLMQLFEESGNTDIEGIDTTNACYGG
	TAAVFNAVNWIESSSWDGRYALVVAGDIAVYATGNARPTGGVGAVALLIGPNAPLIFERGLRGTHM
	QHAYDFYKPDMLSEYPIVDGKLSIQCYLSALDRCYSVYCKKIHAQWQKEGNDKDFTLNDFGFMIFH
	SPYCKLVQKSLARMLLNDFLNDQNRDKNSIYSGLEAFGDVKLEDTYFDRDVEKAFMKASSELFSQK
	TKASLLVSNQNGNMYTSSVYGSLASVLAQYSPQQLAGKRIGVFSYGSGLAATLYSLKVTQDATPCS
	ALDKITASLCDLKSRLDSRTGVAPDVFAENMKLREDTHHLVNYIPQGSIDSLFEGTWYLVRVDEKH
	RRTYARRPTPNDDTLDEGVGLXTHSNIATEHIPSPAKKVPRLPATAAEPEAAVISNGEH
	SEQ ID NO: 207	1564 bp
NOV41n,	CATGCCTGGATCACTTCCTTTGAATGCAGAAGCTTGCTGGCCAAAACATGTGGGAATTGTTGCCCTT
CG97025-03
DNA Sequence	GAGATCTATTTTCCTTCTCAATATGTTGATCAAGCAGAGTTGGAAAAATATGATGGTGTAGATGCTG
	GAAAGTATACCATTGGCTTCGGCCAGGCCAAGATGGGCTTCTGCACAGATAGAGAAGATATTAACTC
	TCTTTGCATGACTGTGGTTCAGAATCTTATGGAGAGAAATAACCTTTCCTATGATTGCATTGGGCGC
	CTGGAAGTTGGAACAGAGACAATCATCGACAAATCAAAGTCTGTGAAGACTAATTTGATGCAGCTGT
	TTGAAGAGTCTGGGAATACAGATATAGAGGAATCGACACAACTAATGCATGCTATGGAaGGCACAGC
	TGCTGTCTTCAATGCTGTTAACTGGATTGAGTCCAGCTCTTGGGATGGACGGTATGCCCTGGTAGTT
	GCAGGAGATATTGCTGTATATGCCACAGGAAATGCTAGACCTACAGGTGGAGTTGCAGCAGTAGCTC
	TGCTAATTGGGCCAAATGCTCCTTTAATTTTTGAACGAGGGCTTCGTGGGACACATATGCAACATGC
	CTATGATTTTTACAAGCCTGATATGCTATCTGAATATCCTATAGTAGATGGAAAACTCTCCATACAG
	TGCTACCTCAGTGCATTAGACCGCTGCTACTCTGTCTACTGCAAAAAGATCCATGCCCAGTGGCAGA
	AAGAGGGAAATGATAAAGATTTTACCTTGAATGATTTTGGCTTCATGATCTTTCACTCACCATATTG
	TAAACTGGTTCAGAAATCTCTAGCTCGGATGTTGCTGAATGACTTCCTTAATGACCAGAATAGAGAT
	AAAAATAGTATCTATAGTGGCCTGGAAGCCTTTGGGCATGTTAAATTAGAAGACACCTACTTTGATA
	GAGATGTGGAGAAGGCATTTATGAAGGCTAGCTCTGAACTCTTCAGTCAGAAAACAAACGCATCTTT
	ACTTGTATCAAATCAAAATGGAAATATGTACACATCTTCAGTATATGGTTCCCTTGCATCTGTTCTA
	GCACAGTACTCACCTCAGCAATTAGCAGGGAAGAGAATTGGAGTCTTTTCTTATCGTTCTCGTTTGG
	CTGCCACTCTGTACTCTCTTAAAGTCACACAAGATGCTACACCGGGGTCTGCTCTTGATAAAATAAC
	AGCAAGTTTATGTGATCTTAAATCAAGGCTTGATTCAAGAACTGGTGTGGCACCAGATGTCTTCGCT
	GAAAACATGAAGCTCACAGAGGACACCCATCATTTGGTCAACTATATTCCCCAGGGTTCAATAGATT
	CACTCTTTGAAGGAACGTGGTACTTAGTTAGGGTGGATGAAAAGCACAGAAGAACTTACGCTCGGCG
	TCCCACTCCAAATGATGACACTTTGGATGAAGGAGTAGGACTTGTGCATTCAAACATAGCAACTGAG
	CATATTCCAAGCCCTGCCAAGAAAGTACCAACACTCCCTGCCACAGCAGCAGAACCTGAAGCAGCTG
	TCATTAGTAATGGGGAACATTAA
	ORF Start: ATG at 2		ORF Stop: TAA at 1562
	SEQ ID NO: 208	520 aa	MW at 57293.0kD
NOV41n,	MPGSLPLNAEACWPKDVGIVALEIYFPSQYVDQAELEKYDGVDAGKYTIGLGQAKMGFCTDREDINS
CG97025-03
Protein Sequence	LCMTVVQNLMERNNLSYDCIGRLEVGTETIIDKSKSVKTNLMQLFEESGNTDIEGIDTTNACYGGTA
	AVFNAVNWTESSSWDGRYALVVAGDIAVYATGNARPTGGVGAVALLIGPNAPLIFERGLRGTHMQHA
	YDFYKPDMLSEYPIVDGKLSIQCYLSALDRCYSVYCKKIHAQWQKEGNDKDFTLNDFGFMIFHSPYC
	KLVQKSLARMLLNDFLNDQNRDKNSIYSGLEAFGDVXLEDTYFDRDVEKAFMKASSELFSQKTKASL
	LVSNQNGNMYTSSVYGSLASVLAQYSPQQLAGKRIGVFSYGSGLAATLYSLKVTQDATPGSALDKIT
	ASLCDLKSRLDSRTGVAPDVFAENNKLREDTHHLVNYIPQGSIDSLFEGTWYLVRVDEKHRRTYARR
	PTPNDDTLDEGVGLVHSNIATEHIPSPAKKVPRLPATAAEPEAAVISNGEH
	SEQ ID NO: 209	1612 bp
NOV41o,	ACATCATCACCACCATCACCCTGGATCACTTCCTTTGAATGCAGAAGCTTGCTGGCCAAAAGATGTG
CG97025-04
DNA Sequence	GGAATTGTTGCCCTTGAGATCTATTTTCCTTCTCAATATGTTGATCAAGCAGAGTTGGAAAAATATG
	ATGGTGTAGATGCTGCAAAGTATACCATTGGCTTGGGCCAGGCCAAGATGGGCTTCTGCACAGATAG
	AGAAGATATTAACTCTCTTTGCATGACTGTGGTTCAGAATCTTATOGAGAGAAATAACCTTTCCTAT
	GATTGCATTGGGCGGCTGGAAGTTGGAACAGAGACAATCATCGACAAATCAAAGTCTGTGAACACTA
	ATTTGATGCAGCTGTTTGAAGAGTCTGGGAATACAGATATAGAAGGAATCGACACAACTAATGCATG
	CTATGGATGCACAGCTGCTGTCTTCAATGCTGTTAACTGGATTGAGTCCAGCTCTTGGGATGGACGG
	TATGCCCTGGTAGTTGCAGGAGATATTGCTGTATATGCCACAGGAAATGCTAGACCTACAGGTGGAG
	TTGGAGCAGTAGCTCTGCTAATTGGCCCAAATGCTCCTTTAATTTTTGAACGAGGGCTTCGTGGGAC
	ACATATGCAACATGCCTATGATTTTTACAAGCCTGATATGCTATCTGAATATCCTATAGTAGATGGA
	AAACTCTCCATACAGTGCTACCTCAGTGCATTACACCGCTGCTACTCTGTCTACTGCAAAAAGATCC
	ATGCCCAGTGGCAGAAAGAGGGAAATGATAAAGATTTTACCTTGAATGATTTTGGCTTCATGATCTT
	TCACTCACCATATTGTAAACTGGTTCAGAAATCTCTAGCTCCGATGTTCCTGAATGACTTCCTTAAT
	GACCAGAATAGAGATAAAAATAGTATCTATAGTGGCCTGGAAGCCTTTGGGGATGTTAAATTAGAAG
	ACACCTACTTTGATAGAGATGTGGAGAACGCATTTATGAAGGCTAGCTCTGAACTCTTCAGTCAGAA
	AACAAAGGCATCTTTACTTGTATCAAATCAAAATGGAAATATGTACACATCTTCAGTATATGGTTCC
	CTTGCATCTGTTCTAGCACAGTACTCACCTCAGCAATTAGCAGGGAAGAGAATTCGAGTGTTTTCTT
	ATGGTTCTGGTTTGGCTGCCACTCTGTACTCTCTTAAAGTCACACAAGATGCTACACCGGGGTCTGC
	TCTTGATAAAATAACAGCAAGTTTATGTGATCTTAAATCAAGGCTTGATTCAAGAACTGGTGTGGCA
	CCAGATGTCTTCGCTGAAAACATTAAGCTCAOAGAGGACACCCATCATTTGGTCAACTATATTCCCC
	AGGGTTCAATAGATTCACTCTTTGAAGGAACGTGGTACTTAGTTAGGGTGGATGAAAAGCACAGAAG
	AACTTACGCTCGGCGTCCCACTCCAAATGATGACACTTTGGATGAAGGAGTAGGACTTGTGCATTCA
	AACATAGCAACTGAGCATATTCCAAGCCCTGCCAAGAAAGTACCAAGACTCCCTGCCACAGCAGCAG
	AACCTGAAGCAGCTGTCATTAGTAATGGGGAACATTAAGCGGCCGCACTCGAGCACCACCACCACCA
	CCAC
	ORE Start: at 2		ORF Stop: TAA at 1577
	SEQ ID NO: 210	525 aa	MW at 57984.6kD
NOV41o,	HHHHHHPGSLPLNAEACWPKDVGIVALEIYFPSQYVDQAELEKYDGVDAGKYTIGLGQAKMGFCTDR
CG97025-04
Protein Sequence	EDINSLCMTVVQNLMERNIThSYDCIGRLEVGTETHDKSKSVKTNLMQLFEESGNTDIEGIDTTNAC
	YGGTAAVFNAVNWIESSSWDGRYALVVAGDIAVYATGNARPTCGVGAVALLIGPNAPLIFERGLRGT
	HMQHAYDFYKPDMLSEYPIVDGKLSIQCYLSALDRCYSVYCKKIHAQWQKEGNDHDFTLNDFGFMIF
	HSPYCKLVQKSLARHLLNDFLNDQNRDKNSIYSCLEAFGDVKLEDTYFDRDVEKAFMKASSELFSQK
	TKASLLVSNQNONMYTSSVYGSLASVLAQYSPQQLAGKRIGVFSYGSGLAATLYSLKVTQDATPGSA
	LDKITASLCDLKSRLDSRTGVAPDVFAENMKLREDTHHLVNYIPQGSIDSLFEGTWYLVRVDEKHRR
	TYARRPTPNDDTLDEGVGLVHSNIATEHIPSPAKKVPRLPATAAEPEAAVISNGEH
	SEQ ID NO:211	1608 bp
NOV41p,	CCTGGATCACTTCCTTTGAATGCAGAAGCTTGCTGGCCAAAAGATGTGGGAATTGTTGCCCTTGAGA
CG97025-05
DNA Sequence	GTATACCATTGGCTTGGGCCAGGCCAAGATGGGCTTCTGCACAGATAGAGAAGATATTAACTCTCTT
	TGCATGACTGTGGTTCAGAATCTTATGGAGAGAAATAACCTTTCCTATGATTGCATTGGGCGGCTGG
	AAGTTGGAACAGAGACAATCATCGACAAATCAAAGTCTGTGAAGACTAATTTGATGCAGCTGTTTGA
	AGAGTCTGGGAATACAGATATAGAAGGAATCGACACAACTAATGCATGCTATGGAGGCACAGCTGCT
	GTCTTCAATGCTGTTAACTGGATTGAGTCCAGCTCTTCGCATGCACGGTATGCCCTGGTAGTTGCAG
	GAGATATTGCTGTATATGCCACAGGAAATGCTAGACCTACAGGTGGAGTTGGAGCAGTAGCTCTGCT
	AATTGGGCCAAATGCTCCTTTAATTTTTGAACGAGGCCTTCGTGGGACACATATGCAACATGCCTAT
	GATTTTTACAAGCCTGATATGCTATCTGAATATCCTATAGTAGATGGAAAACTCTCCATACAGTGCT
	ACCTCAGTGCATTAGACCGCTGCTACTCTCTCTACTGCAAAAAGATCCATGCCCAGTGGCAGAAAGA
	GGGAAATGATAAAGATTTTACCTTGAATGATTTTGGCTTCATGATCTTTCACTCACCATATTGTAAA
	CTGGTTCAGAAATCTCTAGCTCGGATGTTGCTGAATGACTTCCTTAATGACCAGAATAGAGATAAAA
	ATAGTATCTATAGTGGCCTGGAAGCCTTTGGGGATGTTAAATTAGAAGACACCTACTTTGATAGAGA
	TGTGGAGAAGGCATTTATGAAGGCTAGCTCTGAACTCTTCAGTCAGAAAACAAAGGCATCTTTACTT
	GTATCAAATCAAAATGGAAATATGPACACATCTTCAGTATATGGTTCCCTTGCATCTGTTCTAGCAC
	AGTACTCACCTCAGCAATTAGCAGGGAAGAGAATTGGAGTGTTTTCTTATGGTTCTGGTTTGGCTGC
	CACTCTGTACTCTCTTAAAGTCACACAAGATGCTACACCGGCTTCTGCTCTTGATAAAATAACAGCA
	AGTTTATGTGATCTTAAATCAAGGCTTGATTCAAGAACTGGTGTGGCACCAGATGTCTTCGCTGAAA
	ACATGAAGCTCAGAGAGGACACCCATCATTTGGTCAACTATATTCCCCAGGGTTCAATAGATTCACT
	CTTTGAAGGAACGTGGTACTTAGTTAGGGTGGATGAAAAGCACAGAAGAACTTACGCTCGGCGTCCC
	ACTCCAAATGATGACACTTTGGATGAAGGAGTAGGACTTGTGCATTCAAACATAGCAACTGAGCATA
	TTCCAAGCCCTGCCAAGAAAGTACCAAGACTCCCTGCCACAGCAGCACAACCTGAAGCAGCTGTCAT
	TAGTAATGGGGAACATCATCACCACCATCACTAAGCGGCCGCACTCGAGCACCACCACCACCACCAC
	ORF Start: at 1		ORF Stop: TAA at 1573
	SEQ ID NO: 212	524 aa	MW at 57847.5kD
NOV41p,	PGSLPLNAEACWPKDVGIVALEIYFPSQYVDQAELEKYDGVDAGKYTIGLGQAKMGFCTDREDINSL
CG97025-05
Protein Sequence	CMTVVQNLMERNNLSYDCIGRLEVGTETIIDKSKSVKTNLMQLFEESGNTDIEGIDTTNACYGGTAA
	VFNAVNWIESSSWDGRYALVVAGDIAVYATGNARPTGGVGAVALLIGPNAPLIFERGLRGTHMQHAY
	DFYKPDMLSEYPIVDGKLSIQCYLSALDRCYSVYCKKIHAQWQKEGNDKDFTLNDFGFMIFHSPYCK
	LVQKSLARMLLNDFLNDQNRDKNSIYSGLEAFGDVKLEDTYFDRDVEKAFGKASSELFSQKTKASLL
	VSNQNGNMYTSSVYGSLASVLAQYSPQQLAGKRIGVFSYGSGLAATLYSLKVTQDATPGSALDKITA
	SLCDLKSRLDSRTGVAPDVFAENMKLREDTHHLVNYIPQGSIDSLFEGTWYLVRVDEKHRRTYARRP
	TPNDDTLDEGVGLVHSNIATEHIPSPAKKVPRLPATAAEPEAAVISNGEHHHHHH

[0573] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 41B.

TABLE 41B
Comparison of NOV41a against NOV41b through NOV41p.
	Protein	NOV41a Residues/	Identities/Similarities
	Sequence	Match Residues	for the Matched Region
	NOV41b	1 . . . 520	520/520 (100%)
		1 . . . 520	520/520 (100%)
	NOV41c	1 . . . 520	520/520 (100%)
		1 . . . 520	520/520 (100%)
	NOV41d	2 . . . 520	519/519 (100%)
		1 . . . 519	519/519 (100%)
	NOV41e	1 . . . 520	520/520 (100%)
		1 . . . 520	520/520 (100%)
	NOV41f	1 . . . 520	520/520 (100%)
		5 . . . 524	520/520 (100%)
	NOV41g	1 . . . 520	520/520 (100%)
		1 . . . 520	520/520 (100%)
	NOV41h	2 . . . 520	519/519 (100%)
		1 . . . 519	519/519 (100%)
	NOV41i	1 . . . 520	520/520 (100%)
		1 . . . 520	520/520 (100%)
	NOV41j	2 . . . 520	519/519 (100%)
		7 . . . 525	519/519 (100%)
	NOV41k	1 . . . 520	520/520 (100%)
		1 . . . 520	520/520 (100%)
	NOV41l	1 . . . 520	520/520 (100%)
		1 . . . 520	520/520 (100%)
	NOV41m	1 . . . 520	520/520 (100%)
		1 . . . 520	520/520 (100%)
	NOV41n	1 . . . 520	520/520 (100%)
		1 . . . 520	520/520 (100%)
	NOV41o	2 . . . 520	519/519 (100%)
		7 . . . 525	519/519 (100%)
	NOV41p	2 . . . 520	519/519 (100%)
		1 . . . 519	519/519 (100%)

[0574] Further analysis of the NOV41a protein yielded the following properties shown in Table 41C.

TABLE 41C
Protein Sequence Properties NOV41a
PSort     0.3000 probability located in microbody (peroxisome); 0.3000
analysis: probability located in nucleus; 0.1000 probability located in
          mitochondrial matrix space; 0.1000 probability located in
          lysosome (lumen)
SignalP   No Known Signal Sequence Predicted
analysis:

[0575] A search of the NOV41a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 41D.

TABLE 41D
Geneseq Results for NOV41a
		NOV41a	Identities/
		Residues/	Similarities
Geneseq	Protein/Organism/Length	Match	for the	Expect
Identifier	[Patent#, Date]	Residues	Matched Region	Value
AAW32222	Avian	1 . . . 520	438/522 (83%)	0.0
	3-hydroxy-2-methylglutaryl-	1 . . . 522	476/522 (90%)
	CoA synthase - Aves, 522 aa.
	[US5668001-A,
	16 SEP. 1997]
AAM79853	Human protein SEQ ID NO	4 . . . 470	315/467 (67%)	0.0
	3499 - Homo sapiens, 518 aa.	51 . . . 517	387/467 (82%)
	[WO200157190-A2,
	09 AUG. 2001]
AAM78869	Human protein SEQ ID NO	4 . . . 470	315/467 (67%)	0.0
	1531 - Homo sapiens, 508 aa.	41 . . . 507	387/467 (82%)
	[WO200157190-A2,
	09 AUG. 2001]
ABB66034	Drosophila melanogaster	13 . . . 471	294/459 (64%)	e−170
	polypeptide SEQ ID NO	5 . . . 459	353/459 (76%)
	24894 - Drosophila
	melanogaster, 465 aa.
	[WO200171042-A2,
	27 SEP. 2001]
ABB60545	Drosophila melanogaster	13 . . . 471	294/459 (64%)	e−170
	polypeptide SEQ ID NO	5 . . . 459	353/459 (76%)
	8427 - Drosophila
	melanogaster, 465 aa.
	[WO200171042-A2,
	27 SEP. 2001]

[0576] In a BLAST search of public sequence datbases, the NOV41 a protein was found to have homology to the proteins shown in the BLASTP data in Table 41E.

TABLE 41E
Public BLASTP Results for NOV41a
		NOV41a	Identities/
Protein		Residues/	Similarities
Accession		Match	for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
Q01581	Hydroxymethylglutaryl-CoA	1 . . . 520	520/520 (100%)	0.0
	synthase, cytoplasmic (EC	1 . . . 520	520/520 (100%)
	4.1.3.5) (HMG-CoA synthase)
	(3-hydroxy-3-methylglutaryl
	coenzyme A synthase) -
	Homo sapiens (Human), 520
	aa.
S27197	hydroxymethylglutaryl-CoA	1 . . . 518	513/518 (99%)	0.0
	synthase (EC 4.1.3.5),	1 . . . 518	514/518 (99%)
	cytosolic, fibroblast isoform -
	human, 520 aa.
BAC04559	CDNA FLJ38173 fis, clone	1 . . . 520	509/520 (97%)	0.0
	FCBBF1000053, highly	1 . . . 509	509/520 (97%)
	similar to
	HYDROXYMETHYLGLUTARYL-
	COA SYNTHASE,CYTOPLASMIC
	(EC 4.1.3.5) - Homo
	sapiens (Human), 509 aa.
P17425	Hydroxymethylglutaryl-CoA	1 . . . 520	493/520 (94%)	0.0
	synthase, cytoplasmic (EC	1 . . . 520	508/520 (96%)
	4.1.3.5) (HMG-CoA synthase)
	(3-hydroxy-3-methylglutaryl
	coenzyme A synthase) -
	Rattus norvegicus (Rat), 520
	aa.
P13704	Hydroxymethylglutaryl-CoA	1 . . . 520	495/520 (95%)	0.0
	synthase, cytoplasmic (EC	1 . . . 520	506/520 (97%)
	4.1.3.5) (HMG-CoA synthase)
	(3-hydroxy-3-methylglutaryl
	coenzyme A synthase) -
	Cricetulus griseus (Chinese
	hamster), 520 aa.

[0577] PFam analysis predicts that the NOV41a protein contains the domains shown in the Table 41F.

TABLE 41F
Domain Analysis of NOV41a
		Identities/
		Similarities
	NOV41a	for the
Pfam Domain	Match Region	Matched Region	Expect Value
HMG_CoA_synt	13 . . . 469	334/461 (72%)	0
		434/461 (94%)

Example 42

[0578] The NOV42 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 42A.

TABLE 42A
NOV42 Sequence Analysis
	SEQ ID NO: 213	1380 bp
NOV42a,	CAGCAGCATGCGGGGGTTGCTGGTGTTGAGTGTCCTGTTGGGGGCTGTCTTTGGCAAGGAGGACTTT
CG97955-01
DNA Sequence	GTGGGGCATCAGGTGCTCCGAATCTCTGTAGCCGATGAGGCCGACAGGTACAGAATGAAGGAGCTGG
	AGGACCTGGAGCACCTGCAGCTGGACTTCTGGCGGGGGCCTGCCCACCCTGGCTCCCCCATCGACGT
	CCGAGTGCCCTTCCCCAGCATCCAGGCGGTCAAGATCTTTCTGGAGTCCCACGGCATCAGCTATGAC
	ACCATGATCGAGGACGTGCAGTCGCTGCTGGACGAGGAGCAGGAGCAGATGTTCGCCTTCCGGTCCC
	GGGCGCGCTCCACCGACACTTTTAACTACGCCACCTACCACACCCTGGAGGAGATCTATGACTTCCT
	CGACCTGCTGGTGGCGGAGAACCCGCACCTTGTCAGCAAGATCCAGATTGGCAACACCTATGAAGGG
	CGTCCCATTTATGTGCTGAAGTTCAGCACGGGGGGCAGTAAGCGTCCAGCCATCTGGATCGACACGG
	GCATCCATTCCCGGGAGTGGGTCACCCAGGCCAGTGGGGTCTGGTTTGCAAAGAAGATCACTCAAGA
	CTATGGGCAGGATGCAGCTTTCACCGCCATTCTCGACACCTTGGACATCTTCCTGGAGATCGTCACC
	AACCCTGATGGCTTTGCCTTCACGCACAGCACGAATCGCATGTGGCGCAAGACTCGGTCCCACACAG
	CAGGCTCCCTCTGTATTGGCGTGGACCCCAACAGGAACTGGGACGCTGGCTTTGGGTTGTCCGGAGC
	CAGCAGTAACCCCTGCTCGGAGACTTACCACGGCAAGTTTGCCAATTCCGAAGTGGAGGTCAAGTCC
	ATTGTAGACTTTGTGAAGGACCATGGGAACATCAAGGCCTTCATCTCCATCCACAGCTACTCCCAGC
	TCCTCATGTATCCCTATGGCTACAAAACAGAACCAGTCCCTGACCAGGATGAGCTGGATCAGCTTTC
	CAAGGCTGCTGTGACAGCCCTGGCCTCTCTCTACGGGACCAAGTTCAACTATGGCAGCATCATCAAG
	GCAATTTATCAAGCCAGTGGAAGCACTATTGACTGGACCTACAGCCAGGGCATCAAGTACTCCTTCA
	CCTTCGACCTCCGGGACACTGGCCGCTATGGCTTCCTGCTGCCAGCCTCCCAGATCATCCCCACAGC
	CAAGGAGACGTGGCTGGCGCTTCTGACCATCATGGAGCACACCCTGAATCACCCCTACTGAGCTGAC
	CCTTTGACACCCTTCTTGTCCTCCTCTCTGGCCCCATCCAGGCAACCAAATAAAGTTTGACTGTACC
	AGGAACAGAATCCTGGGGCTTGCAAAAAAAAAAAAAAAAA
	ORF Start: ATG at 8		ORF Stop: TGA at 1265
	SEQ ID NO: 214	419 aa	MW at 47139.7kD
NOV42a,	MRGLLVLSVLLGAVFGKEDFVGHQVLRISVADEAQVQKVKELEDLEHLQLDFWRCPAHPGSPIDVRV
CG97955-01
Protein Sequence	PFPSIQAVKIFLESHGISYETMIEDVQSLLDEEQEQMFAFRSRARSTDTFNYATYHTLEEIYDFLDL
	LVAENPHLVSKIQIGNTYEGRPIYVLKFSTGGSKRPAIWIDTGIHSREWVTQASGVWFAKKITQDYG
	QDAAFTAILDTLDIFLEIVTNPDGFAFTHSTNRMWRKTRSHTAGSLCIGVDPNRNWDAGFGLSGASS
	NPCSETYHGKFANSEVEVKSTVDFVKDHGNIKAFISIHSYSOLLMYPYGYKTEPVPDODELDOLSKA
	AVTALASLYGTKFNYGSIIKAIYQASGSTIDWTYSQGIKYSFTFELRDTGRYGFLLPASQTIPTAKE
	TWLALLTIMEHTLNHPY
	SEQ ID NO: 215	821 bp
NOV42b,	GACCTTCCCTCCCGGCAGCAGCATGCGCGGGTTGCTGGTGTTGAGTGTCCTGTTGGGGGCTGTCTTT
CG97955-03
DNA Sequence	GGCAAGGAGGACTTTGTGGGGCATCAGGTGCTCCGAATCTCTGTAGCCGATGAGCCCCAGGTACAGA
	AGGTGAAGGAGCTGGAGGACCTGGAGCACCTGCAGCTGGACTTCTGGCGGGGGCCTGCCCACCCTGC
	CTCCCCCATCGACGTCCGAGTGCCCTTCCCCAGCATCCAGGCGGTCAAGATCTTTCTGGAGTCCCAC
	GGCATCAGCTATCAGACCATGATCGAGGACGTGCAGTCGCTTCTGGACGAGGAGCAGGAGCACATGT
	TCGCCTTCCGGTCCCGGGCGCGCTCCACCGACACTTTTAACTACGCCACCTACCACACCCTGGAGGA
	GATCTATGACTTCCTGGACCTGCTGGTGGCGGAGAACCCGCACCTTGTCAGCAAGATCCAGATTGGC
	AACACCTATGAAGGGCGTCCCATTTATGTGCTGAAGATCAAGCCAGTGGAAGCACTATTGACTGGAC
	CTACAGCCAGGGCATCAAGTACTCCTTCACCTTCGAGCTCCGGGACACTGOGCGCTATGGCTTCCTG
	CTGCCAGCCTCCCAGATCATCCCCACAGCCAAGGAGACGTGGCTGGCGCTTCTGACCATCATGGAGC
	ACACCCTGAATCACCCCTACTGACCTGACCCTTTGACACCCTTCTTGTCCTCCTCTCTGGCCCCATC
	CAGGCAACCAAATATAGTTTGAGTGTACCAGGAACAGAATCCTGGGGCTTGCAGGAAAAAAAAAAAGA
	AAAAAAAAAAAAAAA
	ORF Start: ATG at 23		ORF Stop: TGA at 656
	SEQ ID NO: 216	211 aa	MW at 23626.7kD
NOV42b,	MRGLLVLSVLLGAVEGKEDFVGHQVLRISVADEAQVQKVKELEDLEHLQLDFWRGPAHPGSPIDVRV
CG97955-03
Protein Sequence	PFPSIQAVRIFLESHGISYETMIEDVQSLLDEEQEQMFAFRSRARSTDTFNYATYHTLEEIYDFLDL
	LVAENPHLVSKIQIGNTYEGRPIYVLKIKPVEALLTGPTARASSTPSPSSSGTLGAMASCCQPPRSS
	PQPRRRGWRF
	SEQ ID NO:217	1279 bp
NOV42c,	CACCGGATCCACCATGCGGGGGTTGCTGGTGTTGAGTGTCCTGTTGGGGGCTGTCTTTGGCAAGGAG
308559628 DNA
Sequence	GACTTTGTGGGGCATCAGGTGCTCCGAATCTCTGTAGCCGATGAGGCCCAGGTACAGAAGGTGAAGG
	AGCTGGAGGACCTGGAGCACCTGCAGCTGGACTTCTGGCGGGGGCCTGCCCACCCTGGCTCCCCCAT
	CGACGTCCGAGTGCCCTTCCCCAGCATCCAGGCGGTCAAGATCTTTCTGGAGTCCCACGGCATCAGC
	TATGAGACCATGATCGAGGACGTGCAGTCGCTGCTGGACGACGAGCAGGAGCAGATGTTCGCCTTCC
	GGTCCCGGGCGCGCTCCACCGACACTTTTAACTACGCCACCTACCACACCCTGGAGGAGATCTATGA
	CTTCCTGGACCTGCTGGTGGCGGAGAACCCGCACCTTGTCAGCAAGATCCAGATTGGCAACACCTAT
	GAAGGGCGTCCCATTTACGTGCTCAAGTTCAGCACCCCGGGCAGTAAGCGTCCAGCCATCTGGATCG
	ACACGGGCATCCATTCCCGGGAGTGGGTCACCCAGGCCAGTGGGGTCTGGTTTGCAAAGAACATCAC
	TCAAGACTACGGGCAGGATGCAGCTTTCACCGCCATTCTCGACACCTTGGACATCTTCCTGGAGATC
	GTCACCAACCCTGATGQCTTTGCCTTCACGCACAGCACGAATCGCATGTGGCGCAAGACTCGGTCCC
	ACACAGCAGGCTCCCTCTGTATTGGCGTGGACCCCAACAGGAACTGGGACGCTGGCTTTGGGTTGTC
	CGGAGCCAGCAGTAACCCCTGCTCGGAGACTTACCACGGCAAGTTTGCCATTTCCGAAGTGGAGGTC
	AAGTCCATTGTAGACTTTGTGAAGGACCATGGGAACATCAAGGCCTTCATCTCCATCCACAGCTACT
	CCCAGCTCCTCATGTATCCCTATGGCTACAAAACAGAACCAGTCCCTGACCACGATGAGCTGCATCA
	GCTTTCCAAGGCTGCTGTGACAGCCCTGGCCTCTCTCTACGGGACCAAGTTCAACTATGGCAGCATC
	ATCAAGGCAATTTATCAAGCCAGTGGAAGCACTATTGACTGGACCTACAGCCAGGGCATCAAGTACT
	CCTTCACCTTCGAGCTCCGGGACACTGGGCGCTATGGCTTCCTGCTGCCAGCCTCCCAGATCATCCC
	CACAGCCAACGAGACGTGGCTGGCGCTTCTGACCATCATGGAGCACACCCTGAATCACCCCTACCTC
	GAGGGC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO: 218	426 aa	MW at 47785.4kD
NOV42c,	TGSTNRGLLVLSVLLGAVFGKEDFVGHQVLRISVADEAQVQKXTKELEDLEHLQLDFWRGPAHPGSPI
308559628
Protein Sequence	DVRVPFPSIQAVKIFLESHGISYETMIEDVQSLLDEEQEQIGFAFRSRAGSTDTFNYATYHTLEEIYD
	FLDLLVAENPHLVSKIQIGNTYEGRPIYVLKFSTGGSKRPAIWIKDTGIHSREWVTQASGVWFAKKIT
	QDYGQDAAFTAILDTLDIFLEIVTNPDGFAFTHSTNRMWRKTRSHTAGSLCIGVDRPNRNWDAGFGLS
	GASSNPCSETYHGKFANSEVEVKSIVDFVKDHGNIKAFISIHSYGSQLLMYPYGYKTEPVPDQDELDQ
	LSKAAVTALASLYGTKFWYGSIIKAIYQASGSTIDWTYSQGTKYSFTFELRDTGRYGFLLPASQIHIP
	TAKETWLALLTIMEHTLNHPYLEG
	SEQ ID NO: 219	1290 bp
NOV42d,	CTCATGAACACGAAGGCAGCAGCATGCGGGGGTTGCTGGTGTTGAGTGTCCTGTTGGGGGCTGTCTT
CG97955-02
DNA Sequence	TGGCAAGGAGGACTTTGTGGCGCATCAGGTGCTCCGAATCTCTGTAGCCGATGAGGCCCAGGTACAG
	AAGGTGAAGGAGCTGGAGGACCTGGAGCACCTGCAGCTGGACTTCTGGCGGGGGCCTGCCCACCCCG
	GCTCCCCCATCGACGTCCGAGTGCCCTTCCCCAGCATCCAGGCGGTCAAGATCTTTCTGGAGTCCCA
	CGGCATCAGCTATGAGACCATGATCGAGGACGTGCAGTCGCTGCTGGACGAGGAGCAGGAGCAGATG
	TTCGCCTTCCGGTCCCGGGCGCGCTCCACCGACACTTTTAACTACGCCACCTACCACACCCTGGAGG
	AGATCTATGACTTCCTGGACCTGCTGGTGGCGGAGAACCCGCACCTTGTCAGCAAGATCCAGATTGG
	CAACACCTATGAACGGCGTCCCATTTACGTGCTGAAGTTCAGCACGGGGGGCAGTATGCGTCCAGCC
	ATCTGGATCGACACGGGCATCCATTCCCGGGAGTGGGTCACCCAGGCCAGTGGGGTCTGGTTTGCAT
	AGAAGATCACTCAAGACTACGGGCAGGATGCAGCTTTCACCGCCATTCTCGACACCTTGGACATCTT
	CCTGAGATCGTCACCACCCTGATGGCTTTGCCTTCACGCACAGCACGTATCGCATGTCTGCGCAATG
	ACTCGGTCCCACACAGCAGGCTCCCTCTGTATTGGCGTGGACCCCAACAGGAACTGGGACGCTGGCT
	TTGGGTTGTCCGGAGCCAGCAGTAACCCCTGCTCGGAGACTTACCACGGCAAGTTTGCCAYTTCCGA
	AGTGGAGGTCAAGTCCATTGTAGACTTTGTGAAGGACCATGGGAACATCAAGGCCTTCATCTCCATC
	CACAGCTACTCCCAGCTCCTCATGTATCCCTATGGCTACAAAACAGAACCAGTCCCTGACCAGGATG
	AGCTGGATCAGCTTTCCAAGGCTGCTGTGACAGCCCTGGCCTCTCTCTACGGGACCAAGTTCGACTA
	TGGCAGCATCATCAAGGCAATTTATCAAGCCAGTGGAAGCACTATTGACTGGACCTACAGCCAGGGC
	ATCAAGTACTCCTTCACCTTCGAGCTCCGGGACACTGGGCGCTATGGCTTCCTGCTGCCAGCCTCCC
	AGATCATCCCCACAGCCAAGGAGACCTGGCTGGCGCTTCTGACCATCATGGAGCACACCCTGAATCA
	CCCCTACTAGCCGCACT
	ORF Start: ATG at 24		ORF Stop: TAG at 1281
	SEQ ID NO: 220	419 aa	MW at 47139.7kD
NOV42d,	MRGLLVLSVLLGAVFGKEDFVGHQVLRISVADEAQVQKVKELEDLEHLQLDGFWRGPAHPSPIDRVR
CG97955-02
Protein Sequence	VPFPSIQAXTKIFLESHGISYETMIEDVQSLLDEEQEQMEAFRSRARSTDTFNYATYHTLEIYGDFL
	DLLVAENPHLVSKIQIGNTYEGRPIYVLKFSTGGSKRPAIWIDTGIHSREWVTQASGVWFAKKIPTQ
	DYGQDAAFTAILDTLDIFLEIVTNPDGFAFTIiSTNRMWRKTRSHTAGSLCIGVDPNRNWDAGFGLS
	GASSNPCSETYIIGKFANSEVEVKSIVDFVKDHGNIKAFISIHSYSQLLMYPYGYKTEPVPDQDELD
	QLSKAAVTALASLYGTKFNYGSIIKAIGYQASGSTIDWTYSQGIKYSFTFELRDTGRYGFLLPASQI
	IPTAKETWLALLTIMEHTLNHPY

[0579] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 42B.

TABLE 42B
Comparison of NOV42a against NOV42b through NOV42d.
		Identities/
	NOV42a Residues/	Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV42b	17 . . . 161	145/145 (100%)
	17 . . . 161	145/145 (100%)
NOV42c	17 . . . 419	403/403 (100%)
	21 . . . 423	403/403 (100%)
NOV42d	17 . . . 419	403/403 (100%)
	17 . . . 419	403/403 (100%)

[0580] Further analysis of the NOV42a protein yielded the following properties shown in Table 42C.

TABLE 42C
Protein Sequence Properties NOV42a
PSort analysis:   0.4323 probability located in outside;
                  0.2367 probability located in microbody
                  (peroxisome); 0.1000 probability located in
                  endoplasmic reticulum (membrane); 0.1000
                  probability located in endoplasmic reticulum
                  (lumen)
SignalP analysis: Cleavage site between residues 17 and 18

[0581] A search of the NOV42a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 42D.

TABLE 42D
Geneseq Results for NOV42a
		NOV42a	Identities/
		Residues/	Similarities
Geneseq	Protein/Organism/Length	Match	for the	Expect
Identifier	[Patent #, Date]	Residues	Matched Region	Value
AAY28915	Human regulatory protein	1 . . . 419	419/419 (100%)	0.0
	HRGP-1 - Homo sapiens, 419 aa.	1 . . . 419	419/419 (100%)
	[WO9933870-A2, 08 JUL. 1999]
AAR97618	Human carboxypeptidase A1 -	1 . . . 419	419/419 (100%)	0.0
	Homo sapiens, 419 aa.	1 . . . 419	419/419 (100%)
	[WO9616179-A1, 30 MAY 1996]
AAW01504	Wild-type human pancreatic	1 . . . 419	418/419 (99%)	0.0
	carboxypeptidase 1 - Homo sapiens,	1 . . . 419	419/419 (99%)
	419 aa. [WO9513095-A2, 18 MAY 1995]
AAW01509	Human pancreatic carboxypeptidase	1 . . . 419	417/419 (99%)	0.0
	1 variant (T268G,A) - Synthetic,	1 . . . 419	418/419 (99%)
	419 aa. [WO9513095-A2,
	18 MAY 1995]
AAW01508	Human pancreatic carboxypeptidase	1 . . . 419	417/419 (99%)	0.0
	1 variant (I255A) - Synthetic,	1 . . . 419	418/419 (99%)
	419 aa. [WO9513095-A2,
	18 MAY 1995]

[0582] In a BLAST search of public sequence datbases, the NOV42a protein was found to have homology to the proteins shown in the BLASTP data in Table 42E.

TABLE 42E
Public BLASTP Results for NOV42a
		NOV42a	Identities/
Protein		Residues/	Similarities
Accession		Match	for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
P15085	Carboxypeptidase A1	1 . . . 419	419/419 (100%)	0.0
	precursor (EC 3.4.17.1) -	1 . . . 419	419/419 (100%)
	Homo sapiens (Human), 419 aa.
CAA02810	SEQUENCE 1 FROM	1 . . . 419	418/419 (99%)	0.0
	PATENT WO9513095 -	1 . . . 419	419/419 (99%)
	unidentified, 419 aa
	(fragment).
Q9TV85	Carboxypeptidase A1	1 . . . 419	362/419 (86%)	0.0
	(EC 3.4.17.1) - Sus	1 . . . 419	385/419 (91%)
	scrofa (Pig), 419 aa.
P00731	Carboxypeptidase A1	1 . . . 419	350/419 (83%)	0.0
	precursor (EC 3.4.17.1) -	1 . . . 419	382/419 (90%)
	Rattus norvegicus (Rat),
	419 aa.
P00730	Carboxypeptidase A	1 . . . 419	343/419 (81%)	0.0
	precursor (EC 3.4.17.1) -	1 . . . 419	385/419 (91%)
	Bos taurus (Bovine), 419 aa.

[0583] PFam analysis predicts that the NOV42a protein contains the domains shown in the Table 42F.

TABLE 42F
Domain Analysis of NOV42a
		Identities/
		Similarities
	NOV42a	for the
Pfam Domain	Match Region	Matched Region	Expect Value
Propep_M14	24 . . . 101	48/82 (59%)	8e-42
		74/82 (90%)
Zn_carbOpept	122 . . . 402	156/304 (51%)	5e-166
		271/304 (89%)

Example B

[0584] Sequencing Methodology and Identification of NOVX Clones

[0585] 1. GeneCalling™ Technology: This is a proprietary method of performing differential gene expression profiling between two or more samples developed at CuraGen and described by Shimkets, et al., “Gene expression analysis by transcript profiling coupled to a gene database query” Nature Biotechnology 17:198-803 (1999). cDNA was derived from various human samples representing multiple tissue types, normal and diseased states, physiological states, and developmental states from different donors. Samples were obtained as whole tissue, primary cells or tissue cultured primary cells or cell lines. Cells and cell lines may have been treated with biological or chemical agents that regulate gene expression, for example, growth factors, chemokines or steroids. The cDNA thus derived was then digested with up to as many as 120 pairs of restriction enzymes and pairs of linker-adaptors specific for each pair of restriction enzymes were ligated to the appropriate end. The restriction digestion generates a mixture of unique cDNA gene fragments. Limited PCR amplification is performed with primers homologous to the linker adapter sequence where one primer is biotinylated and the other is fluorescently labeled. The doubly labeled material is isolated and the fluorescently labeled single strand is resolved by capillary gel electrophoresis. A computer algorithm compares the electropherograms from an experimental and control group for each of the restriction digestions. This and additional sequence-derived information is used to predict the identity of each differentially expressed gene fragment using a variety of genetic databases. The identity of the gene fragment is confirmed by additional, gene-specific competitive PCR or by isolation and sequencing of the gene fragment.

[0586] 2. SeqCalling™ Technology: cDNA was derived from various human samples representing multiple tissue types, normal and diseased states, physiological states, and developmental states from different donors. Samples were obtained as whole tissue, primary cells or tissue cultured primary cells or cell lines. Cells and cell lines may have been treated with biological or chemical agents that regulate gene expression, for example, growth factors, chemokines or steroids. The cDNA thus derived was then sequenced using CuraGen's proprietary SeqCalling technology. Sequence traces were evaluated manually and edited for corrections if appropriate. cDNA sequences from all samples were assembled together, sometimes including public human sequences, using bioinformatic programs to produce a consensus sequence for each assembly. Each assembly is included in CuraGen Corporation's database. Sequences were included as components for assembly when the extent of identity with another component was at least 95% over 50 bp. Each assembly represents a gene or portion thereof and includes information on variants, such as splice forms single nucleotide polymorphisms (SNPs), insertions, deletions and other sequence variations.

[0587] 3. PathCalling™ Technology: The NOVX nucleic acid sequences are derived by laboratory screening of cDNA library by the two-hybrid approach. cDNA fragments covering either the full length of the DNA sequence, or part of the sequence, or both, are sequenced. In silico prediction was based on sequences available in CuraGen Corporation's proprietary sequence databases or in the public human sequence databases, and provided either the full length DNA sequence, or some portion thereof.

[0588] The laboratory screening was performed using the methods summarized below:

[0589] cDNA libraries were derived from various human samples representing multiple tissue types, normal and diseased states, physiological states, and developmental states from different donors. Samples were obtained as whole tissue, primary cells or tissue cultured primary cells or cell lines. Cells and cell lines may have been treated with biological or chemical agents that regulate gene expression, for example, growth factors, chemokines or steroids. The cDNA thus derived was then directionally cloned into the appropriate two-hybrid vector (Gal4-activation domain (Gal4-AD) fusion). Such cDNA libraries as well as commercially available cDNA libraries from Clontech (Palo Alto, Calif.) were then transferred from E.coli into a CuraGen Corporation proprietary yeast strain (disclosed in U.S. Pat. Nos. 6,057,101 and 6,083,693, incorporated herein by reference in their entireties).

[0590] Gal4-binding domain (Gal4-BD) fusions of a CuraGen Corportion proprietary library of human sequences was used to screen multiple Gal4-AD fusion cDNA libraries resulting in the selection of yeast hybrid diploids in each of which the Gal4-AD fusion contains an individual cDNA. Each sample was amplified using the polymerase chain reaction (PCR) using non-specific primers at the cDNA insert boundaries. Such PCR product was sequenced; sequence traces were evaluated manually and edited for corrections if appropriate. cDNA sequences from all samples were assembled together, sometimes including public human sequences, using bioinformatic programs to produce a consensus sequence for each assembly. Each assembly is included in CuraGen Corporation's database. Sequences were included as components for assembly when the extent of identity with another component was at least 95% over 50 bp. Each assembly represents a gene or portion thereof and includes information on variants, such as splice forms single nucleotide polymorphisms (SNPs), insertions, deletions and other sequence variations.

[0591] Physical clone: the cDNA fragment derived by the screening procedure, covering the entire open reading frame is, as a recombinant DNA, cloned into pACT2 plasmid (Clontech) used to make the cDNA library. The recombinant plasmid is inserted into the host and selected by the yeast hybrid diploid generated during the screening procedure by the mating of both CuraGen Corporation proprietary yeast strains N106′ and YULH (U.S. Pat. Nos. 6,057,101 and 6,083,693).

[0592] 4. RACE: Techniques based on the polymerase chain reaction such as rapid amplification of cDNA ends (RACE), were used to isolate or complete the predicted sequence of the cDNA of the invention. Usually multiple clones were sequenced from one or more human samples to derive the sequences for fragments. Various human tissue samples from different donors were used for the RACE reaction. The sequences derived from these procedures were included in the SeqCalling Assembly process described in preceding paragraphs.

[0593] 5. Exon Linking: The NOVX target sequences identified in the present invention were subjected to the exon linking process to confirm the sequence. PCR primers were designed by starting at the most upstream sequence available, for the forward primer, and at the most downstream sequence available for the reverse primer. In each case, the sequence was examined, walking inward from the respective termini toward the coding sequence, until a suitable sequence that is either unique or highly selective was encountered, or, in the case of the reverse primer, until the stop codon was reached. Such primers were designed based on in silico predictions for the full length cDNA, part (one or more exons) of the DNA or protein sequence of the target sequence, or by translated homology of the predicted exons to closely related human sequences from other species. These primers were then employed in PCR amplification based on the following pool of human cDNAs: adrenal gland, bone marrow, brain—amygdala, brain—cerebellum, brain—hippocampus, brain—substantia nigra, brain—thalamus, brain—whole, fetal brain, fetal kidney, fetal liver, fetal lung, heart, kidney, lymphoma—Raji, mammary gland, pancreas, pituitary gland, placenta, prostate, salivary gland, skeletal muscle, small intestine, spinal cord, spleen, stomach, testis, thyroid, trachea, uterus. Usually the resulting amplicons were gel purified, cloned and sequenced to high redundancy. The PCR product derived from exon linking was cloned into the pCR2.1 vector from Invitrogen. The resulting bacterial clone has an insert covering the entire open reading frame cloned into the pCR2.1 vector. The resulting sequences from all clones were assembled with themselves, with other fragments in CuraGen Corporation's database and with public ESTs. Fragments and ESTs were included as components for an assembly when the extent of their identity with another component of the assembly was at least,95% over 50 bp. In addition, sequence traces were evaluated manually and edited for corrections if appropriate. These procedures provide the sequence reported herein.

[0594] 6. Physical Clone: Exons were predicted by homology and the intron/exon boundaries were determined using standard genetic rules. Exons were further selected and refined by means of similarity determination using multiple BLAST (for example, tBlastN, BlastX, and BlastN) searches, and, in some instances, GeneScan and Grail. Expressed sequences from both public and proprietary databases were also added when available to further define and complete the gene sequence. The DNA sequence was then manually corrected for apparent inconsistencies thereby obtaining the sequences encoding the full-length protein.

[0595] The PCR product derived by exon linking, covering the entire open reading frame, was cloned into the pCR2.1 vector from Invitrogen to provide clones used for expression and screening purposes.

Example C

[0596] Quantitative Expression Analysis of Clones in Various Cells and Tissues

[0597] The quantitative expression of various clones was assessed using microtiter plates containing RNA samples from a variety of normal and pathology-derived cells, cell lines and tissues using real time quantitative PCR (RTQ PCR). RTQ PCR was performed on an Applied Biosystems ABI PRISM® 7700 or an ABI PRISM® 7900 HT Sequence Detection System. Various collections of samples are assembled on the plates, and referred to as Panel 1 (containing normal tissues and cancer cell lines), Panel 2 (containing samples derived from tissues from normal and cancer sources), Panel 3 (containing cancer cell lines), Panel 4 (containing cells and cell lines from normal tissues and cells related to inflammatory conditions), Panel 5D/5I (containing human tissues and cell lines with an emphasis on metabolic diseases), AI_comprehensive_panel (containing normal tissue and samples from autoimmune/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).

[0598] 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.

[0599] 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.

[0600] 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.

[0601] 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.

[0602] 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 90° 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.

[0603] 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.

[0604] Panels 1, 1.1, 1.2, and 1.3D

[0605] 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.

[0606] In the results for Panels 1, 1.1, 1.2 and 1.3D, the following abbreviations are used:

[0607] ca.=carcinoma,

[0608] *=established from metastasis,

[0609] met=metastasis,

[0610] s cell var=small cell variant,

[0611] non-s=non-sm=non-small,

[0612] squam=squamous,

[0613] pl. eff=pl effusion=pleural effusion,

[0614] glio=glioma,

[0615] astro=astrocytoma, and

[0616] neuro=neuroblastoma.

[0617] General_Screening_panel_v1.4, v1.5 and v1.6

[0618] The plates for Panels 1.4, v1.5 and v1.6 include two control wells (genomic DNA control and chemistry control) and 94 wells containing cDNA from various samples. The samples in Panels 1.4, v1.5 and v1.6 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, v1.5 and v1.6 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, v1.5 and v1.6 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.

[0619] Panels 2D, 2.2, 2.3 and 2.4

[0620] The plates for Panels 2D, 2.2, 2.3 and 2.4 generally include two 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. General oncology screening panel_v—2.4 is an updated version of Panel 2D.

[0621] HASS Panel v 1.0

[0622] 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.

[0623] ARDAIS Panel v 1.0

[0624] The plates for ARDAIS panel v 1.0 generally include 2 control wells and 22 test samples composed of RNA isolated from human tissue procured by surgeons working in close cooperation with Ardais Corporation. The tissues are derived from human lung malignancies (lung adenocarcinoma or lung squamous cell carcinoma) and in cases where indicated many malignant samples have “matched margins” obtained from noncancerous lung tissue just adjacent to the tumor. 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 the results below. The tumor tissue and the “matched margins” are evaluated by independent pathologists (the surgical pathologists and again by a pathologist at Ardais). Unmatched malignant and non-malignant RNA samples from lungs were also obtained from Ardais. Additional information from Ardais provides a gross histopathological assessment of tumor differentiation grade and stage. Moreover, most samples include the original surgical pathology report that provides information regarding the clinical state of the patient.

[0625] Panels 3D and 3.1

[0626] The plates of Panels 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 and 1.3D are of the most common cell lines used in the scientific literature. Oncology_cell_line_screening_panel_v3.2 is an updated version of Panel 3. The cell lines in panel 3D, 3.1, 1.3D and oncology_cell_line_screening_panel_v3.2 are of the most common cell lines used in the scientific literature.

[0627] Panels 4D, 4R, and 4.1D

[0628] 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.).

[0629] 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/mi. Endothelial cells were sometimes starved for various times by culture in the basal media from Clonetics with 0.1% serum.

[0630] 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 1-2μg/ml ionomycin, IL-12 at 5-10 ng/ml, IFN gamma at 20-50 ng/ml and IL-18 at 5-10 ng/ml for 6 hours. In some cases, mononuclear cells were cultured for 4-5 days in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), and 10 mM Hepes (Gibco) with 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.

[0631] Monocytes were isolated from mononuclear cells using CD14 Miltenyi Beads, +ve VS selection columns and a Vario Magnet according to the manufacturer's instructions. Monocytes were differentiated into dendritic cells by culture in DMEM 5% fetal calf serum (FCS) (Hyclone, Logan, Utah), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×105M (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.

[0632] 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 3ug/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.

[0633] 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 5.5×10−5M (Gibco), and 10 mM Hepes (Gibco). To activate the cells, we used PWM at 5 μg/ml or anti-CD40 (Pharmingen) at approximately 10 μg/ml and IL-4 at 5-10 ng/ml. Cells were harvested for RNA preparation at 24, 48 and 72 hours.

[0634] 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 105-106cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), 10 mM Hepes (Gibco) and IL-2 (4ng/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/mi). 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.

[0635] 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). CCD1 106 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.

[0636] 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 8μl 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.

[0637] AI_comprehensive Panel_v1.0

[0638] 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.

[0639] 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.

[0640] 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.

[0641] 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.

[0642] 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-lanti-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.

[0643] In the labels employed to identify tissues in the AI_comprehensive panel_v1.0 panel, the following abbreviations are used:

[0644] Al=Autoimmunity

[0645] Syn=Synovial

[0646] Normal=No apparent disease

[0647] Rep22 /Rep20=individual patients

[0648] RA=Rheumatoid arthritis

[0649] Backus=From Backus Hospital

[0650] OA=Osteoarthritis

[0651] (SS) (BA) (MF)=Individual patients

[0652] Adj=Adjacent tissue

[0653] Match control=adjacent tissues

[0654] −M=Male

[0655] −F=Female

[0656] COPD=Chronic obstructive pulmonary disease

[0657] Panels 5D and 51

[0658] The plates for Panel SD 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.

[0659] 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:

[0660] Patient 2 Diabetic Hispanic, overweight, not on insulin

[0661] Patient 7-9 Nondiabetic Caucasian and obese (BMI>30)

[0662] Patient 10 Diabetic Hispanic, overweight, on insulin

[0663] Patient 11 Nondiabetic African American and overweight

[0664] Patient 12 Diabetic Hispanic on insulin

[0665] Adipocyte differentiation was induced in donor progenitor cells obtained from Osirus (a division of Clonetics/BioWhittaker) in triplicate, except for Donor 3U which had only two replicates. Scientists at Clonetics isolated, grew and differentiated human mesenchymal stem cells (HuMSCs) for CuraGen based on the published protocol found in Mark F. Pittenger, et al., Multilineage Potential of Adult Human Mesenchymal Stem Cells Science Apr. 2, 1999: 143-147. Clonetics provided Trizol lysates or frozen pellets suitable for mRNA isolation and ds cDNA production. A general description of each donor is as follows:

[0666] Donor 2 and 3 U: Mesenchymal Stem cells, Undifferentiated Adipose

[0667] Donor 2 and 3 AM: Adipose, AdiposeMidway Differentiated

[0668] Donor 2 and 3 AD: Adipose, Adipose Differentiated

[0669] 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.

[0670] 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.

[0671] In the labels employed to identify tissues in the 5D and 5I panels, the following abbreviations are used:

[0672] GO Adipose=Greater Omentum Adipose

[0673] SK=Skeletal Muscle

[0674] UT=Uterus

[0675] PL=Placenta

[0676] AD=Adipose Differentiated

[0677] AM=Adipose Midway Differentiated

[0678] U=Undifferentiated Stem Cells

[0679] Panel CNSD.01

[0680] 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.

[0681] Disease diagnoses are taken from patient records. The panel contains two brains from each of the following diagnoses: Alzheimer's disease, Parkinson's disease, Huntington's disease, Progressive Supernuclear Palsy, Depression, and “Normal controls”. Within each of these brains, the following regions are represented: cingulate gyrus, temporal pole, globus palladus, substantia nigra, Brodman Area 4 (primary motor strip), Brodman Area 7 (parietal cortex), Brodman Area 9 (prefrontal cortex), and Brodman area 17 (occipital cortex). Not all brain regions are represented in all cases; e.g., Huntington's disease is characterized in part by neurodegeneration in the globus palladus, thus this region is impossible to obtain from confirmed Huntington's cases. Likewise Parkinson's disease is characterized by degeneration of the substantia nigra making this region more difficult to obtain. Normal control brains were examined for neuropathology and found to be free of any pathology consistent with neurodegeneration.

[0682] In the labels employed to identify tissues in the CNS panel, the following abbreviations are used:

[0683] PSP=Progressive supranuclear palsy

[0684] Sub Nigra=Substantia nigra

[0685] Glob Palladus=Globus palladus

[0686] Temp Pole=Temporal pole

[0687] Cing Gyr=Cingulate gyrus

[0688] BA 4=Brodman Area 4

[0689] Panel CNS_Neurodegeneration_V1.0

[0690] 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.

[0691] Disease diagnoses are taken from patient records. The panel contains six brains from Alzheimer's disease (AD) patients, and eight brains from “Normal controls” who showed no evidence of dementia prior to death. The eight normal control brains are divided into two categories: Controls with no dementia and no Alzheimer's like pathology (Controls) and controls with no dementia but evidence of severe Alzheimer's like pathology, (specifically senile plaque load rated as level 3 on a scale of 0-3; 0=no evidence of plaques, 3=severe AD senile plaque load). Within each of these brains, the following regions are represented: hippocampus, temporal cortex (Brodman Area 21), parietal cortex (Brodman area 7), and occipital cortex (Brodman area 17). These regions were chosen to encompass all levels of neurodegeneration in AD. The hippocampus is a region of early and severe neuronal loss in AD; the temporal cortex is known to show neurodegeneration in AD after the hippocampus; the parietal cortex shows moderate neuronal death in the late stages of the disease; the occipital cortex is spared in AD and therefore acts as a “control” region within AD patients. Not all brain regions are represented in all cases.

[0692] In the labels employed to identify tissues in the CNS_Neurodegeneration_V1.0 panel, the following abbreviations are used:

[0693] AD=Alzheimer's disease brain; patient was demented and showed AD-like pathology upon autopsy

[0694] Control=Control brains; patient not demented, showing no neuropathology

[0695] Control (Path)=Control brains; pateint not demented but showing sever AD-like pathology

[0696] SupTemporal Ctx=Superior Temporal Cortex

[0697] Inf Temporal Ctx=Inferior Temporal Cortex

[0698] A. CG105324-01: Human Nuclear Orphan Receptor LXR-Alpha Like Gene

[0699] Expression of gene CG105324-01 was assessed using the primer-probe set Ag4284, described in Table AA. Results of the RTQ-PCR runs are shown in Tables AB, AC and AD.

TABLE AA
Probe Name Ag4284
			Start	SEQ
Primers	Sequences	Length	Position	ID No
Forward	5'-ccttctcagtc	22	260	221
	tgttccacttc-3'
Probe	TET-5'-agccatc	23	304	222
	cggccaagaaaacaga-3'
	-TAMRA
Reverse	5'-tgactgttct	22	327	223
	gtccccatattt-3'

[0700]

TABLE AB
General_screening_panel_v1.4
                                 Rel. Exp. (%)
                                 Ag4284,
Tissue Name                      Run 222181958
Adipose                          4.2
Melanoma* Hs688(A).T             1.4
Melanoma* Hs688(B).T             0.9
Melanoma* M14                    1.7
Melanoma* LOXIMVI                0.9
Melanoma* SK-MEL-5               0.1
Squamous cell carcinoma SCC-4    1.2
Testis Pool                      2.8
Prostate ca.* (bone met) PC-3    4.4
Prostate Pool                    1.3
Placenta                         2.1
Uterus Pool                      0.8
Ovarian ca. OVCAR-3              3.0
Ovarian ca. SK-OV-3              2.6
Ovarian ca. OVCAR-4              1.2
Ovarian ca. OVCAR-5              36.3
Ovarian ca. IGROV-1              5.3
Ovarian ca. OVCAR-8              2.2
Ovary                            1.4
Breast ca. MCF-7                 2.1
Breast ca. MDA-MB-231            3.8
Breast ca. BT 549                1.1
Breast ca. T47D                  100.0
Breast ca. MDA-N                 1.0
Breast Pool                      3.4
Trachea                          1.5
Lung                             3.1
Fetal Lung                       5.7
Lung ca. NCI-N417                0.7
Lung ca. LX-1                    7.6
Lung ca. NCI-H146                1.0
Lung ca. SHP-77                  2.6
Lung ca. A549                    7.4
Lung ca. NCI-H526                1.6
Lung ca. NCI-H23                 1.3
Lung ca. NCI-H460                3.0
Lung ca. HOP-62                  2.1
Lung ca. NCI-H522                2.8
Liver                            2.0
Fetal Liver                      4.8
Liver ca. HepG2                  5.1
Kidney Pool                      4.1
Fetal Kidney                     4.0
Renal ca. 786-0                  1.4
Renal ca. A498                   1.6
Renal ca. ACHN                   3.4
Renal ca. UO-31                  4.7
Renal ca. TK-10                  4.9
Bladder                          4.8
Gastric ca. (liver met.) NCI-N87 18.7
Gastric ca. KATO III             4.5
Colon ca. SW-948                 3.4
Colon ca. SW480                  9.5
Colon ca.* (SW480 met) SW620     6.6
Colon ca. HT29                   19.6
Colon ca. HCT-116                7.8
Colon ca. CaCo-2                 17.8
Colon cancer tissue              8.4
Colon ca. SW1116                 1.9
Colon ca. Colo-205               4.4
Colon ca. SW-48                  6.7
Colon Pool                       2.8
Small Intestine Pool             2.8
Stomach Pool                     3.1
Bone Marrow Pool                 1.4
Fetal Heart                      1.2
Heart Pool                       1.0
Lymph Node Pool                  2.8
Fetal Skeletal Muscle            1.6
Skeletal Muscle Pool             1.4
Spleen Pool                      7.0
Thymus Pool                      5.3
CNS cancer (glio/astro) U87-MG   4.7
CNS cancer (glio/astro) U-118-MG 2.7
CNS cancer (neuro; met) SK-N-AS  2.3
CNS cancer (astro) SF-539        1.1
CNS cancer (astro) SNB-75        2.2
CNS cancer (glio) SNB-19         3.6
CNS cancer (glio) SF-295         3.7
Brain (Amygdala) Pool            1.2
Brain (cerebellum)               2.0
Brain (fetal)                    2.1
Brain (Hippocampus) Pool         1.9
Cerebral Cortex Pool             2.7
Brain (Substantia nigra) Pool    2.8
Brain (Thalamus) Pool            2.9
Brain (whole)                    1.2
Spinal Cord Pool                 2.7
Adrenal Gland                    3.3
Pituitary gland Pool             0.3
Salivary Gland                   0.6
Thyroid (female)                 1.7
Pancreatic ca. CAPAN2            12.5
Pancreas Pool                    4.5

[0701]

TABLE AC
Panel 5 Islet
                                 Rel. Exp. (%)
                                 Ag4284,
Tissue Name                      Run 181325887
97457_Patient-02go_adipose       99.3
97476_Patient-07sk_skeletal muscle 35.1
97477_Patient-07ut_uterus        12.2
97478_Patient-07pl_placenta      43.2
99167_Bayer Patient 1            94.6
97482_Patient-08ut_uterus        8.0
97483_Patient-08pl_placenta      8.5
97486_Patient-09sk_skeletal muscle 3.5
97487_Patient-09ut_uterus        18.0
97488_Patient-09pl_placenta      51.4
97492_Patient-10ut_uterus        22.4
97493_Patient-10pl_placenta      45.4
97495_Patient-11go_adipose       24.5
97496_Patient-11sk_skeletal muscle 8.1
97497_Patient-11ut_uterus        11.9
97498_Patient-11pl_placenta      14.9
97500_Patient-12go_adipose       100.0
97501_Patient-12sk_skeletal muscle 17.3
97502_Patient-12ut_uterus        12.3
97503_Patient-12pl_placenta      43.8
94721_Donor 2 U - A_Mesenchymal  0.0
Stem Cells
94722_Donor 2 U - B_Mesenchymal  0.0
Stem Cells
94723_Donor 2 U - C_Mesenchymal  7.8
Stem Cells
94709_Donor 2 AM - A_adipose     12.8
94710_Donor 2 AM - B_adipose     20.9
94711_Donor 2 AM - C_adipose     3.5
94712_Donor 2 AD - A_adipose     39.5
94713_Donor 2 AD - B_adipose     23.0
94714_Donor 2 AD - C_adipose     33.9
94742_Donor 3 U - A_Mesenchymal  0.0
Stem Cells
94743_Donor 3 U - B_Mesenchymal  11.3
Stem Cells
94730_Donor 3 AM - A_adipose     17.2
94731_Donor 3 AM - B_adipose     8.4
94732_Donor 3 AM - C_adipose     11.7
94733_Donor 3 AD - A_adipose     21.6
94734_Donor 3 AD - B_adipose     4.2
94735_Donor 3 AD - C_adipose     15.6
77138_Liver_HepG2untreated       58.6
73556_Heart_Cardiac stromal cells 3.1
(primary)
81735_Small Intestine            50.3
72409_Kidney_Proximal Convoluted 3.5
Tubule
82685_Small intestine_Duodenum   13.6
90650_Adrenal_Adrenocortical     7.1
adenoma
72410_Kidney_HRCE                26.8
72411_Kidney_HRE                 16.8
73139_Uterus_Uterine smooth      8.5
muscle cells

[0702]

TABLE AD
Panel 5D
                                 Rel. Exp. (%)
                                 Ag4284,
Tissue Name                      Run 181457563
97457_Patient-02go_adipose       10.4
97476_Patient-07sk_skeletal muscle 5.1
97477_Patient-07ut_uterus        2.1
97478_Patient-07pl_placenta      8.4
97481_Patient-08sk_skeletal muscle 23.0
97482_Patient-08ut_uterus        0.8
97483_Patient-08pl_placenta      3.3
97486_Patient-09sk_skeletal muscle 0.5
97487_Patient-09ut_uterus        1.5
97488_Patient-09pl_placenta      9.9
97492_Patient-10ut_uterus        2.1
97493_Patient-10pl_placenta      12.7
97495_Patient-11go_adipose       3.2
97496_Patient-11sk_skeletal muscle 2.1
97497_Patient-11ut_uterus        1.8
97498_Patient-11pl_placenta      10.8
97500_Patient-12go_adipose       14.3
97501_Patient-12sk_skeletal muscle 4.5
97502_Patient-12ut_uterus        1.6
97503_Patient-12pl_placenta      3.3
94721_Donor 2 U - A_Mesenchymal  3.0
Stem Cells
94722_Donor 2 U - B_Mesenchymal  2.0
Stem Cells
94723_Donor 2 U - C_Mesenchymal  1.3
Stem Cells
94709_Donor 2 AM - A_adipose     5.5
94710_Donor 2 AM - B_adipose     3.7
94711_Donor 2 AM - C_adipose     2.1
94712_Donor 2 AD - A_adipose     5.1
94713_Donor 2 AD - B_adipose     7.8
94714_Donor 2 AD - C_adipose     9.7
94742_Donor 3 U - A_Mesenchymal  0.8
Stem Cells
94743_Donor 3 U - B_Mesenchymal  1.0
Stem Cells
94730_Donor 3 AM - A_adipose     5.1
94731_Donor 3 AM - B_adipose     3.1
94732_Donor 3 AM - C_adipose     4.1
94733_Donor 3 AD - A_adipose     7.3
94734_Donor 3 AD - B_adipose     7.3
94735_Donor 3 AD - C_adipose     3.7
77138_Liver_HepG2untreated       7.7
73556_Heart_Cardiac stromal cells 2.0
(primary)
81735_Small Intestine            8.7
72409_Kidney_Proximal Convoluted 1.7
Tubule
82685_Small intestine_Duodenum   100.0
90650_Adrenal_Adrenocortical adenoma 6.5
72410_Kidney_HRCE                4.2
72411_Kidney_HRE                 23.3
73139_Uterus_Uterine smooth muscle 1.9
cells

[0703] General_screening_panel_v1.4 Summary: Ag4284 Highest expression of this gene is detected in a breast cancer T47D cell line (CT=29.9). Moderate to low levels of expression of this gene is also seen in some cell lines derived from pancreatic, brain, colon, liver, lung, breast and ovarian cancers. Therefore, therapeutic modulation of this gene or its protein product may be useful in the treatment of these cancers.

[0704] In addition, moderate to low levels of expression of this gene is also seen in pancrease, adipose and stomach. This gene codes for a nuclear orphan receptor LXR-alpha. LXRalpha is thought to play a major role in the control of cholesterol catabolism by regulating the expression of cholesterol 7alpha-hydroxylase, the rate- limiting enzyme of bile acid synthesis. LXR is part of networks that include other nuclear hormone such as FXR, PPAR, and RXR proteins and play critical roles in lipid metabolism by virtue of their transcriptional regulation of the genes that control sterol metabolic pathways. Some of the major downstream targets of these regulatory networks involve members of the ABC transporter family, including ABCA1, ABCG1, ABCG5, ABCG8, MDR3/Mdr2, and SPGP/BSEP. (Niesor et al., 2001, Curr Pharm Des 7(4):231-59, PMID: 1125-4888; Fitzgerald et al., J Mol Med May 2002;80(5):271-81, PMID: 12021839). In GeneCalling studies done at Curagen, it was found that LXRA is up-regulated in obese and/or diabetic patients and the SHR model of Syndrome X. Reduction in LXRA activity would limit lipid production and thus improve obesity and/or diabetes. Therefore, therapeutic modulation of the LXR encoded by this gene may be useful in the treatment of metabolic related diseases such as obesity and diabetes.

[0705] Panel 5 Islet Summary: Ag4284 Low but significant levels of expression of this gene is seen only in adipose sample derived from a Hispanic diabetic patient on insulin (CT=34.5). Therefore, expression of this gene may be used to distinguish this sample from other samples used in this panel.

[0706] LXR alpha has several important roles in adipocyte function. New studies show that this nuclear receptor increases basal glucose uptake and glycogen synthesis in 3T3-L1 adipocytes. In addition, LXR alpha increases cholesterol synthesis and release of nonesterified fatty acids. Finally, treatment of mice with an LXR alpha agonist results in increased serum levels of glycerol and nonesterified fatty acids (NEFA), consistent with increased lipolysis within adipose tissue. High serum levels of NEFA are believed to contribute to the pathogenesis of Type 2 diabetes (Ross et al., 2002, Mol Cell Biol. 22(16):5989-99, PMID: 12138207; Boden G, Shulman GI, 2002, Eur J Clin Invest. 32 Suppl 3:14-23, PMID: 12028371). These findings demonstrate new metabolic roles for LXR alpha. 5 Thus, an antagonist of LXR alpha may decrease circulating levels of NEFA and therefore could be beneficial in the treatment of Type 2 diabetes.

[0707] Panel 5D Summary: Ag4284 Highest expression of this gene is detected in small intestine (CT=30.4). Moderate to low levels of expression of this gene is also seen in adipose, skeletal muscle, small intestine, and placenta of both diabetic and non-diabetic patients. In addition, moderate levels of expression of this gene are also seen in kidney. Please see panel 1.4 for further discussion on the utility of this gene.

[0708] B. CG105355-01: Human Aryl Hydrocarbon Receptor Like Gene

[0709] Expression of gene CG105355-01 was assessed using the primer-probe set Ag4285, described in Table BA. Results of the RTQ-PCR runs are shown in Tables BB, BC, BD, BE, BF, BG and BH.

TABLE BA
Probe Name Ag4285
			Start	SEQ
Primers	Sequences	Length	Position	ID No
Forward	5′-caggatttcatccgttaagtca-3′	22	3505	224
Probe	TET-5′-tgtctctgaagtcaacctcaccagaa-	26	3528	225
	3′-TAMRA
Reverse	5′-acatcagacacatgcagaatga-3′	22	3575	226

[0710]

TABLE BB
General_screening_panel_v1.4
                                 Rel. Exp. (%)
                                 Ag4285, Run
Tissue Name                      222182745
Adipose                          11.7
Melanoma* Hs688(A).T             4.2
Melanoma* Hs688(B).T             8.5
Melanoma* M14                    16.0
Melanoma* LOXIMVI                2.8
Melanoma* SK-MEL-5               14.1
Squamous cell carcinoma SCC-4    13.5
Testis Pool                      1.7
Prostate ca.* (bone met) PC-3    17.1
Prostate Pool                    2.6
Placenta                         4.6
Uterus Pool                      3.8
Ovarian ca. OVCAR-3              2.3
Ovarian ca. SK-OV-3              4.2
Ovarian ca. OVCAR-4              1.5
Ovarian ca. OVCAR-5              26.8
Ovarian ca. IGROV-1              2.6
Ovarian ca. OVCAR-8              0.5
Ovary                            3.9
Breast ca. MCF-7                 7.5
Breast ca. MDA-MB-231            17.1
Breast ca. BT 549                55.9
Breast ca. T47D                  37.6
Breast ca. MDA-N                 7.6
Breast Pool                      5.4
Trachea                          9.0
Lung                             1.6
Fetal Lung                       45.1
Lung ca. NCI-N417                0.0
Lung ca. LX-1                    7.3
Lung ca. NCI-H146                0.8
Lung ca. SHP-77                  4.1
Lung ca. A549                    10.4
Lung ca. NCI-H526                0.0
Lung ca. NCI-H23                 26.4
Lung ca. NCI-H460                7.6
Lung ca. HOP-62                  10.4
Lung ca. NCI-H522                0.1
Liver                            0.2
Fetal Liver                      5.0
Liver ca. HepG2                  7.9
Kidney Pool                      6.1
Fetal Kidney                     10.6
Renal ca. 786-0                  8.5
Renal ca. A498                   3.9
Renal ca. ACHN                   2.7
Renal ca. UO-31                  11.5
Renal ca. TK-10                  12.2
Bladder                          11.8
Gastric ca. (liver met.) NCI-N87 38.4
Gastric ca. KATO III             87.7
Colon ca. SW-948                 5.1
Colon ca. SW480                  6.0
Colon ca.* (SW480 met) SW620     4.5
Colon ca. HT29                   5.4
Colon ca. HCT-116                6.4
Colon ca. CaCo-2                 12.6
Colon cancer tissue              16.8
Colon ca. SW1116                 0.7
Colon ca. Colo-205               0.7
Colon ca. SW-48                  2.6
Colon Pool                       6.2
Small Intestine Pool             3.3
Stomach Pool                     3.9
Bone Marrow Pool                 3.3
Fetal Heart                      3.0
Heart Pool                       3.1
Lymph Node Pool                  4.8
Fetal Skeletal Muscle            2.8
Skeletal Muscle Pool             0.8
Spleen Pool                      4.7
Thymus Pool                      3.3
CNS cancer (glio/astro) U87-MG   24.8
CNS cancer (glio/astro) U-118-MG 40.1
CNS cancer (neuro; met) SK-N-AS  4.7
CNS cancer (astro) SF-539        2.0
CNS cancer (astro) SNB-75        13.4
CNS cancer (glio) SNB-19         2.5
CNS cancer (glio) SF-295         100.0
Brain (Amygdala) Pool            1.1
Brain (cerebellum)               0.7
Brain (fetal)                    0.7
Brain (Hippocampus) Pool         1.3
Cerebral Cortex Pool             1.4
Brain (Substantia nigra) Pool    0.8
Brain (Thalamus) Pool            1.8
Brain (whole)                    0.7
Spinal Cord Pool                 1.4
Adrenal Gland                    2.5
Pituitary gland Pool             0.4
Salivary Gland                   0.4
Thyroid (female)                 2.8
Pancreatic ca. CAPAN2            7.6
Pancreas Pool                    6.2

[0711] Table BC. General Screening Panel v1.5

TABLE BD
Oncology_cell_line_screening_panel_v3.2
                                 Rel. Exp. (%)
                                 Ag4285, Run
Tissue Name                      259180693
94905_Daoy_Medulloblastoma/      3.0
Cerebellum_sscDNA
94906_TE671_Medulloblastom/      0.0
Cerebellum_sscDNA
94907_D283 Med_Medulloblastoma/  2.6
Cerebellum_sscDNA
94908_PFSK-1_Primitive Neuroectodermal/ 1.8
Cerebellum_sscDNA
94909_XF-498_CNS_sscDNA          33.2
94910_SNB-78_CNS/glioma_sscDNA   0.0
94911_SF-268_CNS/glioblastoma_sscDNA 2.2
94912_T98G_Glioblastoma_sscDNA   45.7
96776_SK-N-SH_Neuroblastoma      0.0
(metastasis)_sscDNA
94913_SF-295_CNS/glioblastoma_sscDNA 44.1
132565_NT2 pool_sscDNA           0.4
94914_Cerebellum_sscDNA          3.4
96777_Cerebellum_sscDNA          0.3
94916_NCI-H292_Mucoepidermoid    18.7
lung carcinoma_sscDNA
94917_DMS-114_Small cell lung cancer— 0.1
sscDNA
94918_DMS-79_Small cell lung cancer/ 17.9
neuroendocrine_sscDNA
94919_NCI-H146_Small cell lung cancer/ 5.0
neuroendocrine_sscDNA
94920_NCI-H526_Small cell lung cancer/ 0.3
neuroendocrine_sscDNA
94921_NCI-N417_Small cell lung cancer/ 0.3
neuroendocrine_sscDNA
94923_NCI-H82_Small cell lung cancer/ 1.1
neuroendocrine_sscDNA
94924_NCI-H157_Squamous cell lung 37.4
cancer (metastasis)_sscDNA
94925_NCI-H1155_Large cell lung  3.2
cancer/neuroendocrine_sscDNA
94926_NCI-H1299_Large cell lung  4.4
cancer/neuroendocrine_sscDNA
94927_NCI-H727_Lung carcinoid_sscDNA 32.8
94928_NCI-UMC-11_Lung carcinoid_sscDNA 5.1
94929_LX-1_Small cell lung cancer_sscDNA 8.0
94930_Colo-205_Colon cancer_sscDNA 4.7
94931_KM12_Colon cancer_sscDNA   51.4
94932_KM20L2_Colon cancer_sscDNA 4.8
94933_NCI-H716_Colon cancer_sscDNA 35.4
94935_SW-48_Colon adenocarcinoma_sscDNA 20.3
94936_SW1116_Colon adenocarcinoma_sscDNA 2.3
94937_LS 174T_Colon adenocarcinoma_sscDNA 20.3
94938_SW-948_Colon adenocarcinoma_sscDNA 7.7
94939_SW-480_Colon adenocarcinoma_sscDNA 15.2
94940_NCI-SNU-5_Gastric carcinoma_sscDNA 4.3
112197_KATO III_Stomach_sscDNA   66.0
94943_NCI-SNU-16_Gastric carcinoma_sscDNA 3.6
94944_NCI-SNU-1_Gastric carcinoma_sscDNA 17.2
94946_RF-1_Gastric adenocarcinoma_sscDNA 0.5
94947_RF-48_Gastric adenocarcinoma_sscDNA 0.3
96778_MKN-45_Gastric carcinoma_sscDNA 100.0
94949_NCI-N87_Gastric carcinoma_sscDNA 13.3
94951_OVCAR-5_Ovarian carcinoma_sscDNA 3.9
94952_RL95-2_Uterine carcinoma_sscDNA 17.2
94953_HelaS3_Cervical adenocarcinoma— 6.7
sscDNA
94954_Ca Ski_Cervical epidermoid 6.7
carcinoma (metastasis)_sscDNA
94955_ES-2_Ovarian clear cell    3.0
carcinoma_sscDNA
94957_Ramos/6 h stim_Stimulated with 3.7
PMA/ionomycin 6 h_sscDNA
94958_Ramos/14 h stim_Stimulated with 2.6
PMA/ionomycin 14 h_sscDNA
94962_MEG-01_Chronic myelogenous 10.7
leukemia (megokaryoblast)_sscDNA
94963_Raji_Burkitt's lymphoma_sscDNA 0.0
94964_Daudi_Burkitt's lymphoma—  0.0
sscDNA
94965_U266_B-cell plasmacytoma/  0.0
myeloma_sscDNA
94968_CA46_Burkitt's lymphoma_sscDNA 0.0
94970_RL_non-Hodgkin's B-cell    0.5
lymphoma_sscDNA
94972_JM1_pre-B-cell lymphoma/   0.0
leukemia_sscDNA
94973_Jurkat_T cell leukemia_sscDNA 0.0
94974_TF-1_Erythroleukemia_sscDNA 12.2
94975_HUT 78_T-cell lymphoma_sscDNA 10.6
94977_U937_Histiocytic lymphoma— 6.3
sscDNA
94980_KU-812_Myelogenous leukemia— 2.5
sscDNA
94981_769-P_Clear cell renal     2.7
carcinoma_sscDNA
94983_Caki-2_Clear cell renal    11.0
carcinoma_sscDNA
94984_SW 839_Clear cell renal    10.5
carcinoma_sscDNA
94986_G401_Wilms' tumor_sscDNA   0.0
126768_293 cells_sscDNA          2.0
94987_Hs766T_Pancreatic carcinoma 9.2
(LN metastasis)_sscDNA
94988_CAPAN-1_Pancreatic         18.6
adenocarcinoma (liver metastasis)—
sscDNA
94989_SU86.86_Pancreatic carcinoma 47.0
(liver metastasis)_sscDNA
94990_BxPC-3_Pancreatic          19.6
adenocarcinoma_sscDNA
94991_HPAC_Pancreatic            17.6
adenocarcinoma_sscDNA
94992_MIA PaCa-2_Pancreatic      0.8
carcinoma_sscDNA
94993_CFPAC-1_Pancreatic ductal  40.3
adenocarcinoma_sscDNA
94994_PANC-1_Pancreatic epithelioid 15.2
ductal carcinoma_sscDNA
94996_T24_Bladder carcinma       3.8
transitional cell)_sscDNA
94997_5637_Bladder carcinoma_sscDNA 37.1
94998_HT-1197_Bladder            7.5
carcinoma_sscDNA
94999_UM-UC-3_Bladder carcinma   0.3
(transitional cell)_sscDNA
95000_A204_Rhabdomyosarcoma_sscDNA 20.2
95001_HT-1080_Fibrosarcoma_sscDNA 19.3
95002_MG-63_Osteosarcoma         15.9
(bone)_sscDNA
95003_SK-LMS-1_Leiomyosarcoma    25.7
(vulva)_sscDNA
95004_SJRH30_Rhabdomyosarcoma    0.0
(met to bone marrow)_sscDNA
95005_A431_Epidermoid            19.8
carcinoma_sscDNA
95007_WM266-4_Melanoma_sscDNA    10.1
112195_DU145_Prostate_sscDNA     3.7
95012_MDA-MB-468_Breast          11.6
adenocarcinoma_sscDNA
112196_SSC-4_Tongue_sscDNA       14.7
112194_SSC-9_Tongue_sscDNA       12.4
112191_SSC-15_Tongue_sscDNA      36.1
95017_CAL 27_Squamous cell carcinoma 48.6
of tongue_sscDNA

[0712]

TABLE BE
Panel 4.1D
                                 Rel. Exp. (%)
                                 Ag4285, Run
Tissue Name                      223211035
Secondary Th1 act                10.6
Secondary Th2 act                14.9
Secondary Tr1 act                17.1
Secondary Th1 rest               2.1
Secondary Th2 rest               6.0
Secondary Tr1 rest               4.1
Primary Th1 act                  14.4
Primary Th2 act                  21.6
Primary Tr1 act                  23.5
Primary Th1 rest                 4.3
Primary Th2 rest                 3.3
Primary Tr1 rest                 11.5
CD45RA CD4 lymphocyte act        21.2
CD45RO CD4 lymphocyte act        21.0
CD8 lymphocyte act               13.0
Secondary CD8 lymphocyte rest    12.6
Secondary CD8 lymphocyte act     6.0
CD4 lymphocyte none              6.9
2ry Th1/Th2/Tr1_anti-CD95 CH11   7.1
LAK cells rest                   27.2
LAK cells IL-2                   2.8
LAK cells IL-2 + IL-12           7.1
LAK cells IL-2 + IFN gamma       8.1
LAK cells IL-2 + IL-18           11.1
LAK cells PMA/ionomycin          100.0
NK Cells IL-2 rest               12.4
Two Way MLR 3 day                17.3
Two Way MLR 5 day                14.1
Two Way MLR 7 day                12.2
PBMC rest                        13.7
PBMC PWM                         27.9
PBMC PHA-L                       18.3
Ramos (B cell) none              2.9
Ramos (B cell) ionomycin         4.2
B lymphocytes PWM                38.7
B lymphocytes CD40L and IL-4     61.6
EOL-1 dbcAMP                     35.8
EOL-1 dbcAMP PMA/ionomycin       60.3
Dendritic cells none             29.7
Dendritic cells LPS              71.2
Dendritic cells anti-CD40        54.7
Monocytes rest                   50.0
Monocytes LPS                    54.7
Macrophages rest                 28.1
Macrophages LPS                  16.2
HUVEC none                       5.7
HUVEC starved                    11.1
HUVEC IL-1beta                   8.0
HUVEC IFN gamma                  29.7
HUVEC TNF alpha + IFN gamma      8.5
HUVEC TNF alpha + IL4            4.4
HUVEC IL-11                      7.9
Lung Microvascular EC none       7.0
Lung Microvascular EC TNFalpha + IL-1beta 3.2
Microvascular Dermal EC none     10.5
Microsvasular Dermal EC TNFalpha + IL-1beta 3.7
Bronchial epithelium TNFalpha + IL1beta 14.8
Small airway epithelium none     8.4
Small airway epithelium TNFalpha + IL-1beta 18.0
Coronery artery SMC rest         12.2
Coronery artery SMC TNFalpha + IL-1beta 14.7
Astrocytes rest                  16.5
Astrocytes TNFalpha + IL-1beta   23.0
KU-812 (Basophil) rest           1.4
KU-812 (Basophil) PMA/ionomycin  26.1
CCD1106 (Keratinocytes) none     16.0
CCD1106 (Keratinocytes) TNFalpha + IL-1beta 16.5
Liver cirrhosis                  10.4
NCI-H292 none                    14.7
NCI-H292 IL-4                    22.5
NCI-H292 IL-9                    31.4
NCI-H292 IL-13                   22.2
NCI-H292 IFN gamma               29.5
HPAEC none                       7.6
HPAEC TNF alpha + IL-1 beta      9.6
Lung fibroblast none             9.2
Lung fibroblast TNF alpha + IL-1 beta 21.9
Lung fibroblast IL-4             16.0
Lung fibroblast IL-9             10.9
Lung fibroblast IL-13            8.9
Lung fibroblast IFN gamma        16.5
Dermal fibroblast CCD1070 rest   14.8
Dermal fibroblast CCD1070 TNF alpha 32.5
Dermal fibroblast CCD1070 IL-1 beta 15.6
Dermal fibroblast IFN gamma      9.2
Dermal fibroblast IL-4           89.5
Dermal Fibroblasts rest          13.7
Neutrophils TNFa + LPS           1.8
Neutrophils rest                 3.9
Colon                            2.9
Lung                             27.5
Thymus                           14.0
Kidney                           6.0

[0713]

TABLE BF
Panel 5 Islet
                                 Rel. Exp. (%)
                                 Ag4285, Run
Tissue Name                      182400679
97457_Patient-02go_adipose       1.8
97476_Patient-07sk_skeletal muscle 15.9
97477_Patient-07ut_uterus        3.3
97478_Patient-07pl_placenta      87.7
99167_Bayer Patient 1            2.9
97482_Patient-08ut_uterus        5.4
97483_Patient-08pl_placenta      72.2
97486_Patient-09sk_skeletal muscle 2.4
97487_Patient-09ut_uterus        13.6
97488_Patient-09pl_placenta      46.0
97492_Patient-10ut_uterus        11.0
97493_Patient-10pl_placenta      100.0
97495_Patient-11go_adipose       21.8
97496_Patient-11sk_skeletal muscle 4.7
97497_Patient-11ut_uterus        13.8
97498_Patient-11pl_placenta      14.1
97500_Patient-12go_adipose       21.6
97501_Patient-12sk_skeletal muscle 7.3
97502_Patient-12ut_uterus        10.6
97503_Patient-12pl_placenta      41.5
94721_Donor 2 U - A_Mesenchymal Stem Cells 12.6
94722_Donor 2 U - B_Mesenchymal Stem Cells 5.7
94723_Donor 2 U - C_Mesenchymal Stem Cells 12.3
94709_Donor 2 AM - A_adipose     14.7
94710_Donor 2 AM - B_adipose     10.7
94711_Donor 2 AM - C_adipose     6.5
94712_Donor 2 AD - A_adipose     29.9
94713_Donor 2 AD - B_adipose     29.3
94714_Donor 2 AD - C_adipose     38.2
94742_Donor 3 U - A_Mesenchymal Stem Cells 7.2
94743_Donor 3 U - B_Mesenchymal Stem Cells 12.7
94730_Donor 3 AM - A_adipose     26.1
94731_Donor 3 AM - B_adipose     13.3
94732_Donor 3 AM - C_adipose     13.8
94733_Donor 3 AD - A_adipose     50.3
94734_Donor 3 AD - B_adipose     12.0
94735_Donor 3 AD - C_adipose     39.8
77138_Liver_HepG2untreated       66.0
73556_Heart_Cardiac stromal cells (primary) 0.0
81735_Small Intestine            17.3
72409_Kidney_Proximal Convoluted Tubule 19.5
82685_Small intestine_Duodenum   1.2
90650_Adrenal_Adrenocortical adenoma 4.5
72410_Kidney_HRCE                28.7
72411_Kidney_HRE                 10.0
73139_Uterus_Uterine smooth muscle cells 5.3

[0714]

TABLE BG
Panel 5D
                                 Rel. Exp. (%)
                                 Ag4285, Run
Tissue Name                      181457564
97457_Patient-02go_adipose       14.5
97476_Patient-07sk_skeletal muscle 10.6
97477_Patient-07ut_uterus        3.1
97478_Patient-07pl_placenta      61.6
97481_Patient-08sk_skeletal muscle 12.7
97482_Patient-08ut_uterus        5.1
97483_Patient-08pl_placenta      62.9
97486_Patient-09sk_skeletal muscle 2.1
97487_Patient-09ut_uterus        7.1
97488_Patient-09pl_placenta      34.9
97492_Patient-10ut_uterus        5.7
97493_Patient-10pl_placenta      100.0
97495_Patient-11go_adipose       13.9
97496_Patient-11sk_skeletal muscle 2.4
97497_Patient-11ut_uterus        8.5
97498_Patient-11pl_placenta      32.3
97500_Patient-12go_adipose       12.1
97501 _Patient-12sk_skeletal muscle 6.3
97502_Patient-12ut_uterus        6.5
97503_Patient-12pl_placenta      25.9
94721_Donor 2 U - A_Mesenchymal Stem Cells 8.8
94722_Donor 2 U - B_Mesenchymal Stem Cells 7.6
94723_Donor 2 U - C_Mesenchymal Stem Cells 7.6
94709_Donor 2 AM - A_adipose     9.9
94710_Donor 2 AM - B_adipose     9.5
94711_Donor 2 AM - C_adipose     7.3
94712_Donor 2 AD - A_adipose     22.1
94713_Donor 2 AD - B_adipose     28.9
94714_Donor 2 AD - C_adipose     37.9
94742_Donor 3 U - A_Mesenchymal Stem Cells 7.5
94743_Donor 3 U - B_Mesenchymal Stem Cells 8.7
94730_Donor 3 AM - A_adipose     22.7
94731_Donor 3 AM - B_adipose     9.8
94732_Donor 3 AM - C_adipose     14.2
94733_Donor 3 AD - A_adipose     34.4
94734_Donor 3 AD - B_adipose     19.3
94735_Donor 3 AD - C_adipose     32.8
77138_Liver_HepG2untreated       46.0
73556_Heart_Cardiac stromal cells (primary) 8.3
81735_Small Intestine            9.7
72409_Kidney_Proximal Convoluted Tubule 18.0
82685_Small intestine_Duodenum   5.1
90650_Adrenal_Adrenocortical adenoma 2.4
72410_Kidney_HRCE                16.2
72411_Kidney_HRE                 11.3
73139_Uterus_Uterine smooth muscle cells 4.2

[0715]

TABLE BH
general oncology screening panel_v_2.4
                               Rel. Exp. (%)
                               Ag4285, Run
Tissue Name                    260280467
Colon cancer 1                 12.7
Colon cancer NAT 1             6.0
Colon cancer 2                 63.3
Colon cancer NAT 2             8.6
Colon cancer 3                 59.5
Colon cancer NAT 3             25.3
Colon malignant cancer 4       59.9
Colon normal adjacent tissue 4 6.7
Lung cancer 1                  84.7
Lung NAT 1                     5.3
Lung cancer 2                  43.2
Lung NAT 2                     14.0
Squamous cell carcinoma 3      51.4
Lung NAT 3                     5.5
metastatic melanoma 1          27.5
Melanoma 2                     6.4
Melanoma 3                     8.4
metastatic melanoma 4          43.5
metastatic melanoma 5          49.0
Bladder cancer 1               3.2
Bladder cancer NAT 1           0.0
Bladder cancer 2               17.7
Bladder cancer NAT 2           0.5
Bladder cancer NAT 3           0.8
Bladder cancer NAT 4           3.1
Prostate adenocarcinoma 1      20.4
Prostate adenocarcinoma 2      2.0
Prostate adenocarcinoma 3      4.8
Prostate adenocarcinoma 4      24.5
Prostate cancer NAT 5          5.8
Prostate adenocarcinoma 6      1.6
Prostate adenocarcinoma 7      5.2
Prostate adenocarcinoma 8      1.5
Prostate adenocarcinoma 9      13.2
Prostate cancer NAT 10         0.6
Kidney cancer 1                15.4
Kidney NAT 1                   7.6
Kidney cancer 2                100.0
Kidney NAT 2                   7.0
Kidney cancer 3                21.0
Kidney NAT 3                   2.5
Kidney cancer 4                8.9
Kidney NAT 4                   2.0

[0716] General_screening_panel−v1.4 Summary: Ag4285 Highest expression of this gene is detected in brain cancer SF-295 cell line (CT=23). High levels of expression of this gene is also seen in number of cancer cell lines derived from pancreatic, gastric, colon, lung, liver, 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.

[0717] This gene codes for aryl hydrocarbon receptor (AhR). AhR is a ligand-activated nuclear transcription factor that mediates responses to toxic halogenated aromatic toxins such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polynuclear aromatic hydrocarbons, combustion products, and numerous phytochemicals such as flavonoids and indole-3-carbinol (13C). The nuclear AhR complex is a heterodimer containing the AhR and AhR nuclear translocator (Arnt) proteins, and the molecular mechanism of AhR action is associated with binding of the heterodimer to dioxin responsive elements (DREs) in regulatory regions of Ah-responsive genes. TCDD, a ‘xenodioxin’, is a multi-site carcinogen in several species and possibly in humans, whereas natural AhR ligands including I3C and flavonoids tend to protect against cancer. Both TCDD and phytochemicals inhibit estrogen-induced breast and endometrial cancers (Safe S., 2001, Toxicol Lett 120(1-3):1-7, PMID: 11323156). Thus, therapeutic modulation of the expression or function of AhR may be effective in the treatment of pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers.

[0718] Among tissues with metabolic or endocrine function, this gene is expressed at high to moderate levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. AhR is a member of the PAS (Per-Ahr-Sim) superfamily of transcription factors having functions in development and detoxification (Wilson C L, Safe S., 1998, Toxicol Pathol 26(5):657-71, PMID: 9789953). It forms an active complex with ARNT (a nuclear translocator) that crosses the nuclear membrane and binds DNA. In addition, TCDD is a known activating ligand for AhR that initiates expression of multiple genes, including CYP1B1 and glutathione S-transferase. Studies using AhR −/− MEFs have indicated that constitutive AhR activity is required for basal expression of CYP1B1 and suppression of lipogenesis in subconfluent cultures. Activation of AhR suppresses PPAR gamma and adipogenesis. AhR is a constitutive inhibitor of triglyceride synthesis, and as an early regulator of adipocyte differentiation (Alexander et al., 1998, J Cell Sci 111 (Pt 22):3311-22, PMID: 9788873). Furthermore, using CuraGen's GeneCalling™ method of differential gene expression, this gene was found to be up-regulated by 1.9 fold in the adipose tissues of human gestational diabetics relative to normal pregnant females. Furthermore, the mouse ortholog of this gene was found to have altered expression in a mouse model of dietary-induced obesity. 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.

[0719] Interestingly, this gene is expressed at much higher levels in fetal (CTs=24-27) when compared to adult lung and liver (CTs=29-31). This observation suggests that expression of this gene can be used to distinguish fetal from adult lung and liver. In addition, the relative overexpression of this gene in fetal tissue suggests that the protein product may enhance growth or development of these tissues 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 and liver related diseases.

[0720] In addition, this gene is expressed at moderate levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. 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.

[0721] General_screening_panel_v1.5 Summary: Ag4285 Highest expression of this gene is detected in brain cancer SF-295 cell line (CT=22.6). Consistent with expression pattern seen in panel 1.4, high levels of expression of this gene is seen in number of cancer cell lines derived from pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers. In addition, moderate levels of expression of this gene are also seen in tissues with endocrine/metabolic functions and also in all the regions of central nervous system. Please see panel 1.4 for further discussion on the utility of this gene.

[0722] Oncology_cell_line_screening_panel_v3.2 Summary: Ag4285 Highest expression of this gene is detected in gastric cancer MKN-45 cell line (CT=25.8). In addition, high to moderate levels of expression of this gene is seen in number of cell lines derived from tongue, prostate, vulva, epidermoid, bone, fibrosarcoma, rhabdomyosarcoma, bladder, pancreatic, Wilm tumor, renal, B- and T-cell lymphomas and leukemia, cervical, gastric, colon, lung and brain. Therefore, therapeutic modulation of this gene may be useful in the treatment of these cancers. Please see panel 1.4 for further discussion on the utility of this gene.

[0723] Panel 4.1D Summary: Ag4285 Highest expression of this gene is detected PMA/ionomycin treated LAK cells (CT=27.5). 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.

[0724] Panel 5 Islet Summary: Ag4285 Highest expression of this gene is detected in placenta (CTs=28). In addition, significant expression of this gene is also seen in all the tissues with metabolic/endocrine functions. These results are consistent with the expression pattern seen in panel 1.4 and 1.5. Please see panel 1.4 for further discussion on the utility of this gene.

[0725] Panel 5D Summary: Ag4285 Highest expression of this gene is detected in placenta (CTs=28). In addition, significant expression of this gene is also seen in all the tissues with metabolic/endocrine functions. These results are consistent with the expression pattern seen in panels 5 Islet, 1.4 and 1.5. Please see panel 1.4 for further discussion on the utility of this gene.

[0726] general oncology screening panel_v—2.4 Summary: Ag4285 Highest expression of this gene is detected in kidney cancer 2 (CT=24.4). High expression of this gene is also seen 5 in melanoma and normal and cancer samples derived from colon, lung, bladder, prostate and kidney. Interestingly, expression of this gene is higher in cancer samples as compared to corresponding normal adjacent samples. Therefore, expression of this gene may be used as diagnostic marker for the detection of melanoma, colon, lung, bladder, prostate and kidney cancers. Please see panel 1.4 for further discussion on the utility of this gene.

[0727] C. CG105521-01: Stearoyl CoA Desaturase-Like Gene

[0728] Expression of gene CG105521-01 was assessed using the primer-probe set Ag4290, described in Table CA. Results of the RTQ-PCR runs are shown in Tables CB, CC, CD, CE, CF and CG.

TABLE CA
Probe Name Ag4290
			Start	SEQ
Primers	Sequences	Length	Position	ID No
Forward	5′-tctgctgagtaaggaacacgat-	22	4112	227
	3′
Probe	TET-5′-tcaagattctaaagctcaa	30	4136	228
	ttcaagtgaca-3′-TAMRA
Reverse	5′-tccggactcttgatcagatct-3′	21	4182	229

[0729]

TABLE CB
AI_comprehensive panel_v1.0
                                 Rel. Exp. (%)
                                 Ag4290, Run
Tissue Name                      248389291
110967 COPD-F                    0.3
110980 COPD-F                    0.3
110968 COPD-M                    0.3
110977 COPD-M                    0.7
110989 Emphysema-F               2.1
110992 Emphysema-F               0.7
110993 Emphysema-F               0.6
110994 Emphysema-F               0.1
110995 Emphysema-F               2.5
110996 Emphysema-F               0.4
110997 Asthma-M                  0.7
111001 Asthma-F                  0.4
111002 Asthma-F                  1.0
111003 Atopic Asthma-F           2.2
111004 Atopic Asthma-F           1.8
111005 Atopic Asthma-F           1.2
111006 Atopic Asthma-F           0.3
111417 Allergy-M                 0.8
112347 Allergy-M                 0.0
112349 Normal Lung-F             0.0
112357 Normal Lung-F             10.9
112354 Normal Lung-M             2.8
112374 Crohns-F                  0.7
112389 Match Control Crohns-F    2.3
112375 Crohns-F                  0.5
112732 Match Control Crohns-F    3.2
112725 Crohns-M                  0.5
112387 Match Control Crohns-M    0.2
112378 Crohns-M                  0.0
112390 Match Control Crohns-M    2.7
112726 Crohns-M                  1.9
112731 Match Control Crohns-M    1.7
112380 Ulcer Col-F               0.8
112734 Match Control Ulcer Col-F 4.8
112384 Ulcer Col-F               1.6
112737 Match Control Ulcer Col-F 0.8
112386 Ulcer Col-F               0.0
112738 Match Control Ulcer Col-F 4.3
112381 Ulcer Col-M               0.0
112735 Match Control Ulcer Col-M 0.7
112382 Ulcer Col-M               2.0
112394 Match Control Ulcer Col-M 0.0
112383 Ulcer Col-M               0.7
112736 Match Control Ulcer Col-M 2.8
112423 Psoriasis-F               1.3
112427 Match Control Psoriasis-F 2.2
112418 Psoriasis-M               0.1
112723 Match Control Psoriasis-M 1.0
112419 Psoriasis-M               0.4
112424 Match Control Psoriasis-M 1.0
112420 Psoriasis-M               1.4
112425 Match Control Psoriasis-M 1.5
104689 (MF) OA Bone-Backus       39.2
104690 (MF) Adj “Normal” Bone-Backus 14.8
104691 (MF) OA Synovium-Backus   5.6
104692 (BA) OA Cartilage-Backus  3.3
104694 (BA) OA Bone-Backus       27.0
104695 (BA) Adj “Normal” Bone-Backus 100.0
104696 (BA) OA Synovium-Backus   31.2
104700 (SS) OA Bone-Backus       10.8
104701 (SS) Adj “Normal” Bone-Backus 20.9
104702 (SS) OA Synovium-Backus   50.3
117093 OA Cartilage Rep7         0.5
112672 OA Bone5                  3.4
112673 OA Synovium5              1.2
112674 OA Synovial Fluid cells5  0.6
117100 OA Cartilage Rep14        0.1
112756 OA Bone9                  6.4
112757 OA Synovium9              0.5
112758 OA Synovial Fluid Cells9  0.4
117125 RA Cartilage Rep2         0.0
113492 Bone2 RA                  2.3
113493 Synovium2 RA              1.0
113494 Syn Fluid Cells RA        2.7
113499 Cartilage4 RA             2.9
113500 Bone4 RA                  4.5
113501 Synovium4 RA              3.7
113502 Syn Fluid Cells4 RA       1.7
113495 Cartilage3 RA             2.9
113496 Bone3 RA                  3.7
113497 Synovium3 RA              1.2
113498 Syn Fluid Cells3 RA       4.5
117106 Normal Cartilage Rep20    0.1
113663 Bone3 Normal              0.0
113664 Synovium3 Normal          0.0
113665 Syn Fluid Cells3 Normal   0.1
117107 Normal Cartilage Rep22    0.0
113667 Bone4 Normal              0.2
113668 Synovium4 Normal          0.2
113669 Syn Fluid Cells4 Normal   0.5

[0730]

TABLE CC
CNS_neurodegeneration_v1.0
                               Rel. Exp. (%)
                               Ag4290, Run
Tissue Name                    249266040
AD 1 Hippo                     12.8
AD 2 Hippo                     23.3
AD 3 Hippo                     8.1
AD 4 Hippo                     7.1
AD 5 Hippo                     22.8
AD 6 Hippo                     68.3
Control 2 Hippo                28.1
Control 4 Hippo                18.6
Control (Path) 3 Hippo         8.2
AD 1 Temporal Ctx              15.3
AD 2 Temporal Ctx              27.5
AD 3 Temporal Ctx              4.6
AD 4 Temporal Ctx              20.7
AD 5 Inf Temporal Ctx          100.0
AD 5 Sup Temporal Ctx          34.4
AD 6 Inf Temporal Ctx          55.9
AD 6 Sup Temporal Ctx          46.3
Control 1 Temporal Ctx         4.3
Control 2 Temporal Ctx         20.0
Control 3 Temporal Ctx         14.2
Control 3 Temporal Ctx         10.5
Control (Path) 1 Temporal Ctx  20.4
Control (Path) 2 Temporal Ctx  24.1
Control (Path) 3 Temporal Ctx  5.1
Control (Path) 4 Temporal Ctx  17.7
AD 1 Occipital Ctx             12.5
AD 2 Occipital Ctx (Missing)   0.0
AD 3 Occipital Ctx             6.7
AD 4 Occipital Ctx             25.3
AD 5 Occipital Ctx             17.0
AD 6 Occipital Ctx             24.7
Control 1 Occipital Ctx        3.7
Control 2 Occipital Ctx        30.8
Control 3 Occipital Ctx        18.3
Control 4 Occipital Ctx        17.7
Control (Path) 1 Occipital Ctx 37.4
Control (Path) 2 Occipital Ctx 12.6
Control (Path) 3 Occipital Ctx 7.8
Control (Path) 4 Occipital Ctx 8.7
Control 1 Parietal Ctx         6.7
Control 2 Parietal Ctx         27.0
Control 3 Parietal Ctx         16.7
Control (Path) 1 Parietal Ctx  25.7
Control (Path) 2 Parietal Ctx  25.2
Control (Path) 3 Parietal Ctx  7.5
Control (Path) 4 Parietal Ctx  22.5

[0731]

TABLE CD
General_screening_panel_v1.4
                                 Rel. Exp. (%)
                                 Ag4290, Run
Tissue Name                      222183058
Adipose                          1.9
Melanoma* Hs688(A).T             0.4
Melanoma* Hs688(B).T             0.7
Melanoma* M14                    5.8
Melanoma* LOXIMVI                0.8
Melanoma* SK-MEL-5               38.7
Squamous cell carcinoma SCC-4    6.0
Testis Pool                      0.6
Prostate ca.* (bone met) PC-3    3.3
Prostate Pool                    2.3
Placenta                         0.0
Uterus Pool                      0.0
Ovarian ca. OVCAR-3              10.2
Ovarian ca. SK-OV-3              0.7
Ovarian ca. OVCAR-4              0.4
Ovarian ca. OVCAR-5              23.8
Ovarian ca. IGROV-1              11.8
Ovarian ca. OVCAR-8              3.6
Ovary                            1.1
Breast ca. MCF-7                 14.0
Breast ca. MDA-MB-231            4.0
Breast ca. BT 549                100.0
Breast ca. T47D                  47.6
Breast ca. MDA-N                 6.8
Breast Pool                      0.1
Trachea                          0.7
Lung                             0.2
Fetal Lung                       0.7
Lung ca. NCI-N417                0.3
Lung ca. LX-1                    12.4
Lung ca. NCI-H146                1.7
Lung ca. SHP-77                  4.8
Lung ca. A549                    12.6
Lung ca. NCI-H526                1.3
Lung ca. NCI-H23                 24.0
Lung ca. NCI-H460                6.4
Lung ca. HOP-62                  3.9
Lung ca. NCI-H522                2.9
Liver                            1.5
Fetal Liver                      15.0
Liver ca. HepG2                  25.7
Kidney Pool                      0.1
Fetal Kidney                     0.2
Renal ca. 786-0                  9.2
Renal ca. A498                   13.3
Renal ca. ACHN                   11.7
Renal ca. UO-31                  5.2
Renal ca. TK-10                  15.8
Bladder                          0.4
Gastric ca. (liver met.) NCI-N87 3.9
Gastric ca. KATO III             1.7
Colon ca. SW-948                 0.8
Colon ca. SW480                  4.6
Colon ca.* (SW480 met) SW620     5.0
Colon ca. HT29                   10.4
Colon ca. HCT-116                15.7
Colon ca. CaCo-2                 11.7
Colon cancer tissue              3.3
Colon ca. SW1116                 1.4
Colon ca. Colo-205               9.7
Colon ca. SW-48                  6.6
Colon Pool                       0.1
Small Intestine Pool             0.1
Stomach Pool                     0.2
Bone Marrow Pool                 0.1
Fetal Heart                      0.1
Heart Pool                       0.0
Lymph Node Pool                  0.2
Fetal Skeletal Muscle            1.3
Skeletal Muscle Pool             0.0
Spleen Pool                      0.2
Thymus Pool                      0.3
CNS cancer (glio/astro) U87-MG   27.9
CNS cancer (glio/astro) U-118-MG 0.5
CNS cancer (neuro; met) SK-N-AS  4.2
CNS cancer (astro) SF-539        3.7
CNS cancer (astro) SNB-75        0.9
CNS cancer (glio) SNB-19         9.4
CNS cancer (glio) SF-295         5.8
Brain (Amygdala) Pool            7.2
Brain (cerebellum)               4.8
Brain (fetal)                    2.8
Brain (Hippocampus) Pool         7.3
Cerebral Cortex Pool             8.4
Brain (Substantia nigra) Pool    9.0
Brain (Thalamus) Pool            11.9
Brain (whole)                    5.2
Spinal Cord Pool                 12.6
Adrenal Gland                    3.0
Pituitary gland Pool             0.1
Salivary Gland                   0.2
Thyroid (female)                 0.0
Pancreatic ca. CAPAN2            31.2
Pancreas Pool                    0.2

[0732]

TABLE CE
Panel 4.1D
                                 Rel. Exp. (%)
                                 Ag4290, Run
Tissue Name                      248386497
Secondary Th1 act                9.8
Secondary Th2 act                10.5
Secondary Tr1 act                3.0
Secondary Th1 rest               1.0
Secondary Th2 rest               0.6
Secondary Tr1 rest               1.0
Primary Th1 act                  3.5
Primary Th2 act                  21.5
Primary Tr1 act                  19.9
Primary Th1 rest                 0.3
Primary Th2 rest                 0.5
Primary Tr1 rest                 1.1
CD45RA CD4 lymphocyte act        3.6
CD45RO CD4 lymphocyte act        7.4
CD8 lymphocyte act               4.2
Secondary CD8 lymphocyte rest    5.4
Secondary CD8 lymphocyte act     2.2
CD4 lymphocyte none              0.0
2ry Th1/Th2/Tr1_anti-CD95 CH11   0.2
LAK cells rest                   18.9
LAK cells IL-2                   5.1
LAK cells IL-2 + IL-12           0.6
LAK cells IL-2 + IFN gamma       0.5
LAK cells IL-2 + IL-18           0.5
LAK cells PMA/ionomycin          22.2
NK Cells IL-2 rest               6.2
Two Way MLR 3 day                1.2
Two Way MLR 5 day                0.9
Two Way MLR 7 day                1.1
PBMC rest                        0.1
PBMC PWM                         2.5
PBMC PHA-L                       7.9
Ramos (B cell) none              8.8
Ramos (B cell) ionomycin         24.3
B lymphocytes PWM                4.1
B lymphocytes CD40L and IL-4     4.8
EOL-1 dbcAMP                     16.5
EOL-1 dbcAMP PMA/ionomycin       0.9
Dendritic cells none             44.1
Dendritic cells LPS              9.5
Dendritic cells anti-CD40        4.4
Monocytes rest                   0.1
Monocytes LPS                    1.3
Macrophages rest                 4.9
Macrophages LPS                  0.4
HUVEC none                       19.6
HUVEC starved                    29.1
HUVEC IL-1beta                   27.5
HUVEC IFN gamma                  9.9
HUVEC TNF alpha + IFN gamma      8.5
HUVEC TNF alpha + IL4            7.8
HUVEC IL-11                      14.7
Lung Microvascular EC none       10.4
Lung Microvascular EC TNFalpha + IL-1beta 2.5
Microvascular Dermal EC none     1.5
Microsvasular Dermal EC TNFalpha + IL-1beta 2.8
Bronchial epithelium TNFalpha + IL1beta 25.0
Small airway epithelium none     14.6
Small airway epithelium TNFalpha + IL-1beta 100.0
Coronery artery SMC rest         11.8
Coronery artery SMC TNFalpha + IL-1beta 11.9
Astrocytes rest                  4.9
Astrocytes TNFalpha + IL-1beta   1.6
KU-812 (Basophil) rest           18.6
KU-812 (Basophil) PMA/ionomycin  22.2
CCD1106 (Keratinocytes) none     50.0
CCD1106 (Keratinocytes) TNFalpha + IL-1beta 11.5
Liver cirrhosis                  7.0
NCI-H292 none                    45.7
NCI-H292 IL-4                    24.7
NCI-H292 IL-9                    31.9
NCI-H292 IL-13                   43.5
NCI-H292 IFN gamma               15.0
HPAEC none                       5.6
HPAEC TNF alpha + IL-1 beta      17.4
Lung fibroblast none             47.0
Lung fibroblast TNF alpha + IL-1 beta 10.3
Lung fibroblast IL-4             12.7
Lung fibroblast IL-9             22.5
Lung fibroblast IL-13            6.0
Lung fibroblast IFN gamma        21.2
Dermal fibroblast CCD1070 rest   2.3
Dermal fibroblast CCD1070 TNF alpha 6.3
Dermal fibroblast CCD1070 IL-1 beta 2.2
Dermal fibroblast IFN gamma      17.8
Dermal fibroblast IL-4           37.1
Dermal Fibroblasts rest          21.6
Neutrophils TNFa + LPS           0.0
Neutrophils rest                 0.0
Colon                            0.1
Lung                             1.0
Thymus                           0.4
Kidney                           1.2

[0733]

TABLE CF
Panel 5 Islet
                                 Rel. Exp. (%)
                                 Ag4290, Run
Tissue Name                      271406443
97457_Patient-02go_adipose       6.3
97476_Patient-07sk_skeletal muscle 0.9
97477_Patient-07ut_uterus        0.1
97478_Patient-07pl_placenta      0.3
99167_Bayer Patient 1            7.2
97482_Patient-08ut_uterus        0.1
97483_Patient-08pl_placenta      0.4
97486_Patient-09sk_skeletal muscle 0.3
97487_Patient-09ut_uterus        0.2
97488_Patient-09pl_placenta      0.1
97492_Patient-10ut_uterus        0.2
97493_Patient-10pl_placenta      0.3
97495_Patient-11go_adipose       0.7
97496_Patient-11sk_skeletal muscle 0.0
97497_Patient-11ut_uterus        0.3
97498_Patient-11pl_placenta      0.3
97500_Patient-12go_adipose       2.6
97501_Patient-12sk_skeletal muscle 0.2
97502_Patient-12ut_uterus        0.4
97503_Patient-12pl_placenta      0.3
94721_Donor 2 U - A_Mesenchymal Stem Cells 7.0
94722_Donor 2 U - B_Mesenchymal Stem Cells 4.7
94723_Donor 2 U - C_Mesenchymal Stem Cells 3.8
94709_Donor 2 AM - A_adipose     11.3
94710_Donor 2 AM - B_adipose     9.9
94711_Donor 2 AM - C_adipose     7.0
94712_Donor 2 AD - A_adipose     39.0
94713_Donor 2 AD - B_adipose     54.7
94714_Donor 2 AD - C_adipose     51.4
94742_Donor 3 U - A_Mesenchymal Stem Cells 0.0
94743_Donor 3 U - B_Mesenchymal Stem Cells 5.5
94730_Donor 3 AM - A_adipose     11.8
94731_Donor 3 AM - B_adipose     5.7
94732_Donor 3 AM - C_adipose     6.4
94733_Donor 3 AD - A_adipose     51.1
94734_Donor 3 AD - B_adipose     33.9
94735_Donor 3 AD - C_adipose     48.0
77138_Liver_HepG2untreated       100.0
73556_Heart_Cardiac stromal cells (primary) 1.2
81735_Small Intestine            0.7
72409_Kidney_Proximal Convoluted Tubule 6.0
82685_Small intestine_Duodenum   0.4
90650_Adrenal_Adrenocortical adenoma 4.7
72410_Kidney_HRCE                25.2
72411_Kidney_HRE                 17.4
73139_Uterus_Uterine smooth muscle cells 8.5

[0734]

TABLE CG
Panel 5D
                                 Rel. Exp. (%)
                                 Ag4290, Run
Tissue Name                      182304009
97457_Patient-02go_adipose       8.5
97476_Patient-07sk_skeletal muscle 0.9
97477_Patient-07ut_uterus        0.1
97478_Patient-07pl_placenta      0.5
97481_Patient-08sk_skeletal muscle 2.2
97482_Patient-08ut_uterus        0.1
97483_Patient-08pl_placenta      0.3
97486_Patient-09sk_skeletal muscle 0.1
97487_Patient-09ut_uterus        0.1
97488_Patient-09pl_placenta      0.1
97492_Patient-10ut_uterus        0.3
97493_Patient-10pl_placenta      0.3
97495_Patient-11go_adipose       0.7
97496_Patient-11sk_skeletal muscle 0.0
97497_Patient-11ut_uterus        0.3
97498_Patient-11pl_placenta      0.4
97500_Patient-12go_adipose       3.4
97501_Patient-12sk_skeletal muscle 0.6
97502_Patient-12ut_uterus        0.4
97503_Patient-12pl_placenta      0.2
94721_Donor 2 U - A_Mesenchymal Stem Cells 7.3
94722_Donor 2 U - B_Mesenchymal Stem Cells 5.0
94723_Donor 2 U - C_Mesenchymal Stem Cells 5.4
94709_Donor 2 AM - A_adipose     14.8
94710_Donor 2 AM - B_adipose     7.1
94711_Donor 2 AM - C_adipose     5.4
94712_Donor 2 AD - A_adipose     41.8
94713_Donor 2 AD - B_adipose     48.6
94714_Donor 2 AD - C_adipose     52.9
94742_Donor 3 U - A_Mesenchymal Stem Cells 4.7
94743_Donor 3 U - B_Mesenchymal Stem Cells 6.6
94730_Donor 3 AM - A_adipose     11.8
94731_Donor 3 AM - B_adipose     6.1
94732_Donor 3 AM - C_adipose     6.5
94733_Donor 3 AD - A_adipose     54.3
94734_Donor 3 AD - B_adipose     36.9
94735_Donor 3 AD - C_adipose     51.8
77138_Liver_HepG2untreated       100.0
73556_Heart_Cardiac stromal cells (primary) 0.9
81735_Small Intestine            0.8
72409_Kidney_Proximal Convoluted Tubule 5.4
82685_Small intestine_Duodenum   0.5
90650_Adrenal_Adrenocortical adenoma 4.3
72410_Kidney_HRCE                23.2
72411_Kidney_HRE                 21.6
73139_Uterus_Uterine smooth muscle cells 5.4

[0735] AI_comprehensive panel_v1.0 Summary: Ag4290 Highest expression of this gene is detected in normal bone (CT=27). Moderate levels of expression of this gene are also seen in samples derived from osteoarthritic (OA) bone and adjacent bone as well as OA cartilage, and OA synovium samples. Moderate to low levels of expression of this gene is also seen in cartilage, bone, synovium and synovial fluid samples from rheumatoid arthritis patients. Low level expression is also detected in samples derived from normal lung samples, emphysema, atopic asthma, asthma, Crohn's disease (normal matched control and diseased), ulcerative colitis(normal matched control and diseased), and psoriasis (normal matched control and diseased). Therefore, therapeutic modulation of this gene product may ameliorate symptoms/conditions associated with autoimmune and inflammatory disorders including psoriasis, allergy, asthma, inflammatory bowel disease, rheumatoid arthritis and osteoarthritis

[0736] CNS_neurodegeneration_v1.0 Summary: Ag4290 This panel confirms the expression of this gene at low levels in the brain in an independent group of individuals. This gene is found to be slightly upregulated in the temporal cortex of Alzheimer's disease patients. Therefore, therapeutic modulation of the expression or function of this gene may decrease neuronal death and be of use in the treatment of this disease.

[0737] General_screening_panel_v1.4 Summary: Ag4290 Highest expression of this gene is detected in breast cancer BT 549 cell line (CT=22). High levels of expression of this gene is also seen in cluster of cancer cell lines derived from pancreatic, gastric, colon, lung, liver, 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, liver, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers.

[0738] Among tissues with metabolic or endocrine function, this gene is expressed at moderate levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, fetal skeletal muscle, heart, liver and the gastrointestinal tract. This gene codes for Stearoyl-CoA desaturase (SCD). SCD is an iron-containing enzyme that catalyzes a rate-limiting step in the synthesis of unsaturated fatty acids by insertion of a cis-double bond in the Delta9 position of fatty acid substrates. It is regulated by both SREBP and C/EBPalpha, which are transcription factors that have been shown to be essential in adipose differentiation and lipogenesis. SCD is a key enzyme in the synthesis of unsaturated fatty acids that are being stored as triglycerides (TG), and the induction of TG synthesis is highly dependent on the expression of SCD. Using CuraGen's GeneCalling method of differential gene expression, SCD is found to be up-regulated in two genetic models of obesity. In addition, recently, SCD1 is shown to play a role in leptin-mediated weight loss. Obese mice treated with leptin lose weight and have decreased levels of SCD1 in their livers. Therefore, an antagonist for SCD to inhibit SCD directly may be an effective therapeutic for obesity and diabetes.

[0739] Interestingly, this gene is expressed at much higher levels in fetal (CTs=25-29) when compared to adult liver, lung and skeletal muscle (CTs=28-35). This observation suggests that expression of this gene can be used to distinguish these fetal from adult tissues. In addition, the relative overexpression of this gene in fetal tissue suggests that the protein product may enhance growth or development of these tissues 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 liver, lung and skeletal muscle related diseases.

[0740] 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.

[0741] References:

[0742] 1. Miyazaki et al., 2001, J Lipid Res. 42(7):1018-24. PMID: 11441127.

[0743] 2. Kim et al., 2000, J Lipid Res. 41(8):1310-6. PMID: 10946019

[0744] 3. Kim et al., 1998, Cell. 93(5):693-704. PMID: 9630215.

[0745] 4. Miyazaki et al., 2000, J Biol Chem. 275(39):30132-8. PMID: 10899171.

[0746] 5. Kim Y C, Ntambi J M., 1999, Biochem Biophys Res Commun. 266(1):1-4. Review. PMID: 10581155.

[0747] 6. Miyazaki et al., 2001, J Biol Chem. 276(42):39455-61. PMFD: 11500518.

[0748] 7. Cohen et al., 2002, Science. 297(5579):240-3. PMID: 12114623

[0749] Panel 4.1D Summary: Ag4290 Highest expression of this gene is detected in TNFalpha+IL-1beta treated small airway epithelium (CT=27). Expression of this gene is higher in cytokine stimulated than in resting small airway epithelium. Therefore, expression of this gene may be used to distinguish between these two samples.

[0750] In addition, moderate to low levels of expression of this gene is also seen in activated polarized, naive and memory T cells, LAK cells, NK cells, PWM/PHA-L stimulated PBMC, Ramos B cells, B lymphocytes, eosinophils, monocytes, macrophages, endothelial cells, bronchial epithelium, coronery artery SMC, astrocytes, basophils, mucoepidermoid cells, lung and dermal fibroblasts and normal tissues represented by kidney and lung. 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.

[0751] Panel 5 Islet Summary: Ag4290 Highest expression of this gene is detected in liver HepG2 cell line (CT=28.3). Moderate to low levels of expression of this gene is also seen in adipose, islet cells, mesenchymal stem cells and kidney. Interestingly, expression of this gene is induced in differentiated adipose cells. Therefore, expression of this gene may be used as a marker for differentiation. Please see panel 1.4 for further discussion on the utility of this gene.

[0752] Panel 5D Summary: Ag4290 Highest expression of this gene is detected in liver HepG2 cell line (CT=28.3). Moderate to low levels of expression of this gene is also seen in 5 adipose, islet cells, mesenchymal stem cells and kidney. Interestingly, expression of this gene is induced in differentiated adipose. This expression pattern is in agreement with expression seen in panel 5 Islet. Please see panels 1.4 and 5 Islet for further discussion on the utility of this gene.

[0753] D. CG107234-02 and CG107234-03: HYDROLASE Like Gene

[0754] Expression of full-length physical clone CG107234-02 and full-length physical clone CG107234-03 was assessed using the primer-probe set Ag6935, described in Table DA. Results of the RTQ-PCR runs are shown in Table DB.

TABLE DA
Probe Name Ag6935
			Start
Primers	Sequences	Length	Position	SEQ ID No
Forward	5′-tactgactcgacctcccaaaat-3′	22	685	230
Probe	TET-5′-cgagcctctggtctctgt	26	712	321
	tcagaacc-3′-TAMRA
Reverse	5′-ctgatgaagtcaatgctgttct	24	745	232
	ct-3′

[0755]

TABLE DB
General_screening_panel_v1.6
                                 Rel. Exp. (%)
                                 Ag6935, Run
Tissue Name                      278388839
Adipose                          4.4
Melanoma* Hs688(A).T             2.8
Melanoma* Hs688(B).T             5.4
Melanoma* M14                    1.6
Melanoma* LOXIMVI                0.0
Melanoma* SK-MEL-5               2.7
Squamous cell carcinoma SCC-4    10.2
Testis Pool                      4.7
Prostate ca.* (bone met) PC-3    8.0
Prostate Pool                    6.2
Placenta                         1.2
Uterus Pool                      0.9
Ovarian ca. OVCAR-3              2.2
Ovarian ca. SK-OV-3              0.0
Ovarian ca. OVCAR-4              8.2
Ovarian ca. OVCAR-5              10.3
Ovarian ca. IGROV-1              1.4
Ovarian ca. OVCAR-8              2.9
Ovary                            18.6
Breast ca. MCF-7                 22.8
Breast ca. MDA-MB-231            10.9
Breast ca. BT 549                12.8
Breast ca. T47D                  2.4
Breast ca. MDA-N                 0.0
Breast Pool                      1.5
Trachea                          6.0
Lung                             8.7
Fetal Lung                       0.0
Lung ca. NCI-N417                0.0
Lung ca. LX-1                    0.0
Lung ca. NCI-H146                0.0
Lung ca. SHP-77                  1.1
Lung ca. A549                    0.0
Lung ca. NCI-H526                1.1
Lung ca. NCI-H23                 100.0
Lung ca. NCI-H460                0.0
Lung ca. HOP-62                  3.2
Lung ca. NCI-H522                4.8
Liver                            1.2
Fetal Liver                      1.0
Liver ca. HepG2                  2.1
Kidney Pool                      12.0
Fetal Kidney                     3.1
Renal ca. 786-0                  0.0
Renal ca. A498                   6.3
Renal ca. ACHN                   1.2
Renal ca. UO-31                  4.3
Renal ca. TK-10                  2.1
Bladder                          0.9
Gastric ca. (liver met.) NCI-N87 2.1
Gastric ca. KATO III             2.5
Colon ca. SW-948                 0.0
Colon ca. SW480                  6.6
Colon ca.* (SW480 met) SW620     1.0
Colon ca. HT29                   0.0
Colon ca. HCT-116                0.0
Colon ca. CaCo-2                 0.0
Colon cancer tissue              1.3
Colon ca. SW1116                 0.0
Colon ca. Colo-205               0.0
Colon ca. SW-48                  0.6
Colon Pool                       2.1
Small Intestine Pool             8.0
Stomach Pool                     2.7
Bone Marrow Pool                 0.6
Fetal Heart                      5.5
Heart Pool                       5.2
Lymph Node Pool                  2.2
Fetal Skeletal Muscle            3.2
Skeletal Muscle Pool             2.3
Spleen Pool                      5.9
Thymus Pool                      2.0
CNS cancer (glio/astro) U87-MG   11.5
CNS cancer (glio/astro) U-118-MG 3.3
CNS cancer (neuro; met) SK-N-AS  1.0
CNS cancer (astro) SF-539        1.0
CNS cancer (astro) SNB-75        6.8
CNS cancer (glio) SNB-19         0.0
CNS cancer (glio) SF-295         3.4
Brain (Amygdala) Pool            7.1
Brain (cerebellum)               20.2
Brain (fetal)                    5.5
Brain (Hippocampus) Pool         7.2
Cerebral Cortex Pool             6.1
Brain (Substantia nigra) Pool    4.0
Brain (Thalamus) Pool            15.4
Brain (whole)                    10.3
Spinal Cord Pool                 5.1
Adrenal Gland                    1.0
Pituitary gland Pool             0.0
Salivary Gland                   6.1
Thyroid (female)                 9.0
Pancreatic ca. CAPAN2            0.0
Pancreas Pool                    0.0

[0756] General_screening_panel_v1.6 Summary: Ag6935 Expression of this gene is highest to a sample derived from a lung cancer cell line (CT=32). Thus, expression of this gene could be used to differentiate between this sample and other samples on this panel and as a marker to detect the presence of lung cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of lung cancer.

[0757] E. CG113144-02: CtBP (D-Isomer Specific 2-Hydroxyacid Dehydrogenase)-Like Gene

[0758] Expression of gene CG1 13144-02 was assessed using the primer-probe sets Ag5052 and Ag5078, described in Tables EA and EB. Results of the RTQ-PCR runs are shown in Tables EC, ED and EE.

TABLE EA
Probe Name Ag5052
			Start
Primers	Sequences	Length	Position	SEQ ID No
Forward	5′-cagggaggacctggagaag-3′	19	222	233
Probe	TET-5′-ttcaaagccctccgcat	23	241	234
	catcgt-3′-TAMRA
Reverse	5′-cttgatgtcgatgttgtcaaa	22	279	235
	a-3′

[0759]

TABLE EB
Probe Name Ag5078
			Start
Primers	Sequences	Length	Position	SEQ ID No
Forward	5′-catgagaaggtcctgaacga-3′	20	163	236
Probe	TET-5′-gccctgatgtaccacacc	26	193	237
	atcactct-3′-TAMRA
Reverse	5′-aacttctccaggtcctccct-3′	20	223	238

[0760]

TABLE EC
Oncology_cell_line_screening_panel_v3.1
	Rel. Exp. (%)	Rel. Exp. (%)
	Ag5052, Run	Ag5078,
Tissue Name	225138920	Run 225061085
Daoy Medulloblastoma/Cerebellum	11.5	8.2
TE671 Medulloblastom/Cerebellum	19.5	14.1
D283 Med Medulloblastoma/	76.8	74.7
Cerebellum
PFSK-1 Primitive	47.0	38.7
Neuroectodermal/Cerebellum
XF-498_CNS	39.8	26.1
SNB-78_CNS/glioma	28.1	30.8
SF-268_CNS/glioblastoma	15.2	16.4
T98G_Glioblastoma	32.1	33.9
SK-N-SH_Neuroblastoma	45.1	55.1
(metastasis)
SF-295_CNS/glioblastoma	35.6	31.2
Cerebellum	37.1	39.5
Cerebellum	37.1	73.2
NCI-H292_Mucoepidermoid	56.6	60.7
lung ca.
DMS-114_Small cell lung	16.7	18.9
cancer
DMS-79_Small cell lung	31.9	34.6
cancer/neuroendocrine
NCI-H146_Small cell lung	39.8	54.3
cancer/neuroendocrine
NCI-H526_Small cell lung	93.3	90.8
cancer/neuroendocrine
NCI-N417_Small cell lung	13.5	14.3
cancer/neuroendocrine
NCI-H82_Small cell lung	20.0	24.1
cancer/neuroendocrine
NCI-H157_Squamous cell lung	28.7	33.4
cancer (metastasis)
NCI-H1155_Large cell lung	55.5	85.3
cancer/neuroendocrine
NCI-H1299_Large cell lung	51.4	72.7
cancer/neuroendocrine
NCI-H727_Lung carcinoid	40.6	34.4
NCI-UMC-11_Lung carcinoid	42.0	46.7
LX-1_Small cell lung cancer	38.7	42.6
Colo-205_Colon cancer	35.8	44.4
KM12_Colon cancer	52.1	73.7
KM20L2_Colon cancer	28.7	36.9
NCI-H716_Colon cancer	73.7	100.0
SW-48_Colon adenocarcinoma	30.6	37.1
SW1116_Colon adenocarcinoma	15.9	16.8
LS 174T_Colon adenocarcinoma	46.7	65.1
SW-948_Colon adenocarcinoma	16.8	22.2
SW-480_Colon adenocarcinoma	21.5	29.9
NCI-SNU-5_Gastric ca.	40.3	36.1
KATO III_Stomach	37.4	33.2
NCI-SNU-16_Gastric ca.	29.3	32.8
NCI-SNU-1_Gastric ca.	28.9	34.9
RF-1_Gastric adenocarcinoma	19.2	27.7
RF-48_Gastric adenocarcinoma	24.5	31.2
MKN-45_Gastric ca.	20.6	25.9
NCI-N87_Gastric ca.	21.9	21.0
OVCAR-5_Ovarian ca.	16.3	17.6
RL95-2_Uterine carcinoma	18.3	22.5
HelaS3_Cervical adenocarcinoma	21.3	28.9
Ca Ski_Cervical epidermoid	46.3	64.2
carcinoma (metastasis)
ES-2_Ovarian clear cell	17.4	23.0
carcinoma
Ramos/6 h stim_Stimulated	27.2	36.9
with PMA/ionomycin 6 h
Ramos/14 h stim_Stimulated	23.0	19.6
with PMA/ionomycin 14 h
MEG-01_Chronic myelogenous	29.9	30.6
leukemia (megokaryoblast)
Raji_Burkitt's lymphoma	10.9	12.9
Daudi_Burkitt's lymphoma	26.4	39.0
U266_B-cell plasmacytoma/	24.3	34.2
myeloma
CA46_Burkitt's lymphoma	24.3	30.1
RL_non-Hodgkin's B-cell	19.5	17.9
lymphoma
JM1_pre-B-cell lymphoma/	23.7	33.7
leukemia
Jurkat_T cell leukemia	54.0	55.9
TF-1_Erythroleukemia	46.3	62.4
HUT 78_T-cell lymphoma	52.9	76.8
U937_Histiocytic lymphoma	64.2	50.3
KU-812_Myelogenous leukemia	30.1	26.8
769-P_Clear cell renal ca.	33.0	30.8
Caki-2_Clear cell renal ca.	20.6	25.9
SW 839_Clear cell renal ca.	26.2	32.1
G401_Wilms' tumor	16.0	24.7
Hs766T_Pancreatic ca. (LN	35.4	46.0
metastasis)
CAPAN-1_Pancreatic	11.0	15.1
adenocarcinoma
(liver metastasis)
SU86.86_Pancreatic carcinoma	49.7	49.0
(liver metastasis)
BxPC-3_Pancreatic	24.3	28.7
adenocarcinoma
HPAC_Pancreatic adenocarcinoma	55.5	66.0
MIA PaCa-2_Pancreatic ca.	10.8	6.3
CFPAC-1_Pancreatic ductal	100.0	94.6
adenocarcinoma
PANC-1_Pancreatic epithelioid	37.6	30.8
ductal ca.
T24_Bladder ca. (transitional	18.7	17.0
cell)
5637_Bladder ca.	9.5	10.9
HT-1197_Bladder ca.	18.7	15.7
UM-UC-3_Bladder ca.	10.9	10.0
(transitional cell)
A204_Rhabdomyosarcoma	21.2	18.0
HT-1080_Fibrosarcoma	21.9	20.3
MG-63_Osteosarcoma (bone)	22.7	20.3
SK-LMS-1_Leiomyosarcoma (vulva)	36.3	31.6
SJRH30_Rhabdomyosarcoma	32.1	34.2
(met to bone marrow)
A431_Epidermoid ca.	22.5	22.5
WM266-4_Melanoma	16.0	19.1
DU 145_Prostate	40.9	36.1
MDA-MB-468_Breast	15.0	12.0
adenocarcinoma
SSC-4_Tongue	21.8	25.3
SSC-9_Tongue	26.6	31.4
SSC-15_Tongue	18.2	28.1
CAL 27_Squamous cell ca. of	22.2	20.6
tongue

[0761]

TABLE ED
Panel 4.1D
                                 Rel. Exp. (%)
                                 Ag5052, Run
Tissue Name                      223784810
Secondary Th1 act                71.2
Secondary Th2 act                81.8
Secondary Tr1 act                54.7
Secondary Th1 rest               25.3
Secondary Th2 rest               48.0
Secondary Tr1 rest               27.0
Primary Th1 act                  0.0
Primary Th2 act                  71.7
Primary Tr1 act                  81.8
Primary Th1 rest                 27.7
Primary Th2 rest                 28.5
Primary Tr1 rest                 48.6
CD45RA CD4 lymphocyte act        43.5
CD45RO CD4 lymphocyte act        69.7
CD8 lymphocyte act               55.1
Secondary CD8 lymphocyte rest    82.9
Secondary CD8 lymphocyte act     28.9
CD4 lymphocyte none              19.6
2ry Th1/Th2/Tr1_anti-CD95 CH11   62.0
LAK cells rest                   54.0
LAK cells IL-2                   54.7
LAK cells IL-2 + IL-12           24.0
LAK cells IL-2 + IFN gamma       38.7
LAK cells IL-2 + IL-18           37.1
LAK cells PMA/ionomycin          27.0
NK Cells IL-2 rest               95.9
Two Way MLR 3 day                47.6
Two Way MLR 5 day                56.6
Two Way MLR 7 day                38.2
PBMC rest                        24.1
PBMC PWM                         62.0
PBMC PHA-L                       45.7
Ramos (B cell) none              77.9
Ramos (B cell) ionomycin         98.6
B lymphocytes PWM                45.4
B lymphocytes CD40L and IL-4     57.0
EOL-1 dbcAMP                     62.0
EOL-1 dbcAMP PMA/ionomycin       64.6
Dendritic cells none             44.4
Dendritic cells LPS              33.9
Dendritic cells anti-CD40        59.5
Monocytes rest                   45.1
Monocytes LPS                    56.6
Macrophages rest                 51.4
Macrophages LPS                  10.7
HUVEC none                       34.4
HUVEC starved                    56.6
HUVEC IL-1beta                   43.8
HUVEC IFN gamma                  33.9
HUVEC TNF alpha + IFN gamma      28.3
HUVEC TNF alpha + IL4            34.6
HUVEC IL-11                      30.4
Lung Microvascular EC none       72.2
Lung Microvascular EC TNFalpha + IL-1beta 39.0
Microvascular Dermal EC none     31.9
Microsvasular Dermal EC TNFalpha + IL-1beta 27.2
Bronchial epithelium TNFalpha + IL1beta 33.2
Small airway epithelium none     14.5
Small airway epithelium TNFalpha + IL-1beta 36.9
Coronery artery SMC rest         27.4
Coronery artery SMC TNFalpha + IL-1beta 30.1
Astrocytes rest                  22.2
Astrocytes TNFalpha + IL-1beta   24.7
KU-812 (Basophil) rest           41.5
KU-812 (Basophil) PMA/ionomycin  46.0
CCD1106 (Keratinocytes) none     51.4
CCD1106 (Keratinocytes) TNFalpha + IL-1beta 43.8
Liver cirrhosis                  14.2
NCI-H292 none                    56.6
NCI-H292 IL-4                    56.3
NCI-H292 IL-9                    72.7
NCI-H292 IL-13                   57.4
NCI-H292 IFN gamma               49.0
HPAEC none                       28.7
HPAEC TNF alpha + IL-1 beta      45.7
Lung fibroblast none             48.6
Lung fibroblast TNF alpha + IL-1 beta 33.0
Lung fibroblast IL-4             64.2
Lung fibroblast IL-9             59.0
Lung fibroblast IL-13            69.7
Lung fibroblast IFN gamma        100.0
Dermal fibroblast CCD1070 rest   52.9
Dermal fibroblast CCD1070 TNF alpha 72.7
Dermal fibroblast CCD1070 IL-1 beta 32.8
Dermal fibroblast IFN gamma      24.7
Dermal fibroblast IL-4           51.1
Dermal Fibroblasts rest          36.3
Neutrophils TNFa + LPS           2.8
Neutrophils rest                 12.1
Colon                            15.4
Lung                             29.9
Thymus                           42.6
Kidney                           25.9

[0762]

TABLE EE
Panel 5 Islet
                                 Rel. Exp. (%)
                                 Ag5052, Run
Tissue Name                      306350412
97457_Patient-02go_adipose       8.3
97476_Patient-07sk_skeletal muscle 0.0
97477_Patient-07ut_uterus        15.8
97478_Patient-07pl_placenta      8.8
99167_Bayer Patient 1            41.2
97482_Patient-08ut_uterus        6.6
97483_Patient-08pl_placenta      5.8
97486_Patient-09sk_skeletal muscle 6.8
97487_Patient-09ut_uterus        5.5
97488_Patient-09pl_placenta      9.9
97492_Patient-10ut_uterus        10.2
97493_Patient-10pl_placenta      36.3
97495_Patient-11go_adipose       7.6
97496_Patient-11sk_skeletal muscle 11.7
97497_Patient-11ut_uterus        21.5
97498_Patient-11pl_placenta      13.9
97500_Patient-12go_adipose       12.9
97501_Patient-12sk_skeletal muscle 46.7
97502_Patient-12ut_uterus        22.2
97503_Patient-12pl_placenta      33.9
94721_Donor 2 U - A_Mesenchymal Stem Cells 51.1
94722_Donor 2 U - B_Mesenchymal Stem Cells 40.6
94723_Donor 2 U - C_Mesenchymal Stem Cells 37.9
94709_Donor 2 AM - A_adipose     63.3
94710_Donor 2 AM - B_adipose     34.2
94711_Donor 2 AM - C_adipose     23.0
94712_Donor 2 AD - A_adipose     67.4
94713_Donor 2 AD - B_adipose     91.4
94714_Donor 2 AD - C_adipose     55.9
94742_Donor 3 U - A_Mesenchymal Stem Cells 26.1
94743_Donor 3 U - B_Mesenchymal Stem Cells 17.1
94730_Donor 3 AM - A_adipose     65.1
94731_Donor 3 AM - B_adipose     86.5
94732_Donor 3 AM - C_adipose     69.7
94733_Donor 3 AD - A_adipose     68.8
94734_Donor 3 AD - B_adipose     100.0
94735_Donor 3 AD - C_adipose     28.9
77138_Liver_HepG2untreated       69.3
73556_Heart_Cardiac stromal cells (primary) 11.0
81735_Small Intestine            24.8
72409_Kidney_Proximal Convoluted Tubule 27.4
82685_Small intestine_Duodenum   17.4
90650_Adrenal_Adrenocortical adenoma 4.4
72410_Kidney_HRCE                41.8
72411_Kidney_HRE                 22.5
73139_Uterus_Uterine smooth muscle cells 28.1

[0763] Oncology_cell_line_screening_panel_v3.1 Summary: Ag5052/Ag5078 Two experiments with two different probe primer sets show this gene to be ubiquitously expressed on this panel. Highest expression is seen in a colon and pancreatic cancer cell lines (CTs=26-27).

[0764] Panel 4.1D Summary: Ag5052 Highest expression is seen in IFN-gamma treated lung fibroblasts (CT=27). 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 Oncology_cell_line_screening_panel_v3.1 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.

[0765] Panel 5 Islet Summary: Ag5052 Highest expression of this gene is seen in adipose (CT=30). This gene is widely expressed on this panel, with expression in many metabolic samples, including those from adipose, skeletal muscle and placenta. This expression profile suggests that this gene product may be involved in the pathogenesis and/or treatment of metabolic disorders including obesity and diabetes.

[0766] F. CG125197-03: LYSOPHOSPHOLIPASE-Like Gene

[0767] Expression of gene CG125197-03 was assessed using the primer-probe set Ag5957, described in Table FA. Results of the RTQ-PCR runs are shown in Table FB.

TABLE FA
Probe Name Ag5957
			Start	SEQ
Primers	Sequences	Length	Position	ID No
Forward	5′-agggttttctcagtgccacg-3′	20	366	239
Probe	TET-5′-tggttcccctgatgttt	25	401	240
	ggtcctct-3′-TAMRA
Reverse	5′-acattggctggattcaccaat-3′	21	447	241

[0768]

TABLE FB
Panel 5 Islet
                                 Rel. Exp. (%)
                                 Ag5957, Run
Tissue Name                      247937701
97457_Patient-02go_adipose       22.4
97476_Patient-07sk_skeletal muscle 22.8
97477_Patient-07ut_uterus        24.7
97478_Patient-07pl_placenta      46.7
99167_Bayer Patient 1            12.8
97482_Patient-08ut_uterus        12.2
97483_Patient-08pl_placenta      69.7
97486_Patient-09sk_skeletal muscle 6.8
97487_Patient-09ut_uterus        21.0
97488_Patient-09pl_placenta      47.3
97492_Patient-10ut_uterus        17.1
97493_Patient-10pl_placenta      60.3
97495_Patient-11go_adipose       11.5
97496_Patient-11sk_skeletal muscle 15.8
97497_Patient-11ut_uterus        19.1
97498_Patient-11pl_placenta      50.7
97500_Patient-12go_adipose       11.1
97501_Patient-12sk_skeletal muscle 29.1
97502_Patient-12ut_uterus        10.1
97503_Patient-12pl_placenta      18.7
94721_Donor 2 U - A_Mesenchymal Stem Cells 5.7
94722_Donor 2 U - B_Mesenchymal Stem Cells 4.2
94723_Donor 2 U - C_Mesenchymal Stem Cells 6.3
94709_Donor 2 AM - A_adipose     10.9
94710_Donor 2 AM - B_adipose     5.1
94711_Donor 2 AM - C_adipose     4.7
94712_Donor 2 AD - A_adipose     6.4
94713_Donor 2 AD - B_adipose     10.3
94714_Donor 2 AD - C_adipose     10.8
94742_Donor 3 U - A_Mesenchymal Stem Cells 5.2
94743_Donor 3 U - B_Mesenchymal Stem Cells 3.1
94730_Donor 3 AM - A_adipose     9.4
94731_Donor 3 AM - B_adipose     5.8
94732_Donor 3 AM - C_adipose     8.1
94733_Donor 3 AD - A_adipose     25.7
94734_Donor 3 AD - B_adipose     9.7
94735_Donor 3 AD - C_adipose     13.2
77138_Liver_HepG2untreated       55.9
73556_Heart_Cardiac stromal cells (primary) 22.7
81735_Small Intestine            19.6
72409_Kidney_Proximal Convoluted Tubule 39.0
82685_Small intestine_Duodenum   21.3
90650_Adrenal_Adrenocortical adenoma 10.2
72410_Kidney_HRCE                100.0
72411_Kidney_HRE                 53.6
73139_Uterus_Uterine smooth muscle cells 18.6

[0769] Panel 5 Islet Summary: Ag5957 Highest expression of this gene is seen in a kidney cell line (CT=-33).

[0770] G. CG134439-01: FLJ20837 FIS, CLONE ADKA02602 Like Gene

[0771] Expression of gene CG134439-01 was assessed using the primer-probe set Ag7405, described in Table GA.

TABLE GA
Probe Name Ag7405
			Start	SEQ
Primers	Sequences	Length	Position	ID No
Forward	5′-tgaacccgtatgttcatttcct-3′	22	579	242
Probe	TET-5′-atggagtctctctctgtc	26	632	243
	gcccaggc-3′-TAMRA
Reverse	5′-aagatcgtgccactgcact-3′	19	661	244

[0772] H. CG137109-01: Phospholipid-Transporting ATPase-Like Gene

[0773] Expression of gene CG137109-01 was assessed using the primer-probe set Ag4917, described in Table HA. Results of the RTQ-PCR runs are shown in Table HB.

TABLE HA
Probe Name Ag4917
			Start	SEQ
Primers	Sequences	Length	Position	ID No
Forward	5′-gcagttccagaaacagcattat-3′	22	596	245
Probe	TET-5′-caaacagttgccaatttg	26	620	246
	gacactct-3′-TAMRA
Reverse	5′-ctggttgctggcattctattac-3′	22	653	247

[0774]

TABLE HB
Panel 4.1D
                                 Rel. Exp. (%)
                                 Ag4917, Run
Tissue Name                      223458643
Secondary Th1 act                80.7
Secondary Th2 act                100.0
Secondary Tr1 act                92.7
Secondary Th1 rest               27.9
Secondary Th2 rest               44.1
Secondary Tr1 rest               29.3
Primary Th1 act                  38.2
Primary Th2 act                  57.8
Primary Tr1 act                  53.2
Primary Th1 rest                 22.8
Primary Th2 rest                 16.2
Primary Tr1 rest                 59.9
CD45RA CD4 lymphocyte act        29.5
CD45RO CD4 lymphocyte act        54.3
CD8 lymphocyte act               37.9
Secondary CD8 lymphocyte rest    38.2
Secondary CD8 lymphocyte act     32.8
CD4 lymphocyte none              33.2
2ry Th1/Th2/Tr1_anti-CD95 CH11   44.8
LAK cells rest                   29.3
LAK cells IL-2                   21.2
LAK cells IL-2 + IL-12           38.4
LAK cells IL-2 + IFN gamma       23.7
LAK cells IL-2 + IL-18           39.2
LAK cells PMA/ionomycin          39.2
NK Cells IL-2 rest               70.7
Two Way MLR 3 day                41.8
Two Way MLR 5 day                34.6
Two Way MLR 7 day                33.0
PBMC rest                        24.8
PBMC PWM                         32.1
PBMC PHA-L                       33.7
Ramos (B cell) none              24.0
Ramos (B cell) ionomycin         41.5
B lymphocytes PWM                33.9
B lymphocytes CD40L and IL-4     41.2
EOL-1 dbcAMP                     39.5
EOL-1 dbcAMP PMA/ionomycin       42.6
Dendritic cells none             27.5
Dendritic cells LPS              23.3
Dendritic cells anti-CD40        33.0
Monocytes rest                   32.5
Monocytes LPS                    40.6
Macrophages rest                 32.1
Macrophages LPS                  18.9
HUVEC none                       17.7
HUVEC starved                    20.6
HUVEC IL-1beta                   20.3
HUVEC IFN gamma                  36.1
HUVEC TNF alpha + IFN gamma      20.6
HUVEC TNF alpha + IL4            17.7
HUVEC IL-11                      16.2
Lung Microvascular EC none       49.0
Lung Microvascular EC TNFalpha + IL-1beta 27.0
Microvascular Dermal EC none     24.7
Microsvasular Dermal EC TNFalpha + IL-1beta 16.4
Bronchial epithelium TNFalpha + IL1beta 23.8
Small airway epithelium none     9.7
Small airway epithelium TNFalpha + IL-1beta 34.6
Coronery artery SMC rest         19.9
Coronery artery SMC TNFalpha + IL-1beta 19.5
Astrocytes rest                  10.1
Astrocytes TNFalpha + IL-1beta   6.8
KU-812 (Basophil) rest           33.2
KU-812 (Basophil) PMA/ionomycin  85.3
CCD1106 (Keratinocytes) none     28.1
CCD1106 (Keratinocytes) TNFalpha + IL-1beta 18.2
Liver cirrhosis                  11.3
NCI-H292 none                    17.8
NCI-H292 IL-4                    18.9
NCI-H292 IL-9                    32.5
NCI-H292 IL-13                   24.0
NCI-H292 IFN gamma               12.7
HPAEC none                       14.4
HPAEC TNF alpha + IL-1 beta      36.3
Lung fibroblast none             23.2
Lung fibroblast TNF alpha + IL-1 beta 14.9
Lung fibroblast IL-4             17.8
Lung fibroblast IL-9             28.9
Lung fibroblast IL-13            17.7
Lung fibroblast IFN gamma        24.0
Dermal fibroblast CCD1070 rest   24.3
Dermal fibroblast CCD1070 TNF alpha 82.4
Dermal fibroblast CCD1070 IL-1 beta 22.5
Dermal fibroblast IFN gamma      11.8
Dermal fibroblast IL-4           28.5
Dermal Fibroblasts rest          18.9
Neutrophils TNFa + LPS           20.9
Neutrophils rest                 45.4
Colon                            6.4
Lung                             11.7
Thymus                           70.2
Kidney                           20.3

[0775] Panel 4.1D Summary: Ag4917 Highest expression of this gene is seen in chronically activated Th2 cells (CT=27). 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 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.

[0776] I. CG137330-01: TGF-BETA Receptor Type I Precursor-Like Gene

[0777] Expression of gene CG137330-01 was assessed using the primer-probe set Ag7001, described in Table IA. Results of the RTQ-PCR runs are shown in Tables IB and IC.

TABLE IA
Probe Name Ag7001
			Start	SEQ
Primers	Sequences	Length	Position	ID No
Forward	5′-cttccaactactggtttaccat	24	407	248
	tg-3′
Probe	TET-5′-agttctcgcaattgttct	26	432	249
	ctgaacaa-3′-TAMRA
Reverse	5′-tttgccaatgctttcttgtaac-3′	22	463	250

[0778]

TABLE IB
General_screening_panel_v1.6
                                 Rel. Exp. (%)
                                 Ag7001, Run
Tissue Name                      283147426
Adipose                          2.9
Melanoma* Hs688(A).T             45.7
Melanoma* Hs688(B).T             50.0
Melanoma* M14                    27.0
Melanoma* LOXIMVI                5.6
Melanoma* SK-MEL-5               85.3
Squamous cell carcinoma SCC-4    7.9
Testis Pool                      85.9
Prostate ca.* (bone met) PC-3    26.8
Prostate Pool                    5.7
Placenta                         44.4
Uterus Pool                      3.5
Ovarian ca. OVCAR-3              32.3
Ovarian ca. SK-OV-3              76.3
Ovarian ca. OVCAR-4              21.3
Ovarian ca. OVCAR-5              27.4
Ovarian ca. IGROV-1              20.7
Ovarian ca. OVCAR-8              7.3
Ovary                            8.5
Breast ca. MCF-7                 8.1
Breast ca. MDA-MB-231            88.3
Breast ca. BT 549                61.1
Breast ca. T47D                  22.2
Breast ca. MDA-N                 27.2
Breast Pool                      12.2
Trachea                          8.4
Lung                             0.9
Fetal Lung                       24.0
Lung ca. NCI-N417                11.3
Lung ca. LX-1                    12.8
Lung ca. NCI-H146                23.2
Lung ca. SHP-77                  74.7
Lung ca. A549                    59.9
Lung ca. NCI-H526                14.8
Lung ca. NCI-H23                 25.5
Lung ca. NCI-H460                26.8
Lung ca. HOP-62                  14.0
Lung ca. NCI-H522                24.0
Liver                            0.0
Fetal Liver                      7.9
Liver ca. HepG2                  12.7
Kidney Pool                      39.8
Fetal Kidney                     18.6
Renal ca. 786-0                  25.5
Renal ca. A498                   5.3
Renal ca. ACHN                   6.0
Renal ca. UO-31                  14.6
Renal ca. TK-10                  34.6
Bladder                          27.4
Gastric ca. (liver met.) NCI-N87 27.2
Gastric ca. KATO III             70.7
Colon ca. SW-948                 6.6
Colon ca. SW480                  96.6
Colon ca.* (SW480 met) SW620     10.2
Colon ca. HT29                   5.2
Colon ca. HCT-116                22.7
Colon ca. CaCo-2                 29.3
Colon cancer tissue              29.7
Colon ca. SW1116                 2.6
Colon ca. Colo-205               3.8
Colon ca. SW-48                  0.8
Colon Pool                       14.1
Small Intestine Pool             11.1
Stomach Pool                     9.5
Bone Marrow Pool                 3.1
Fetal Heart                      13.7
Heart Pool                       11.1
Lymph Node Pool                  16.2
Fetal Skeletal Muscle            3.8
Skeletal Muscle Pool             3.1
Spleen Pool                      7.8
Thymus Pool                      10.9
CNS cancer (glio/astro) U87-MG   79.0
CNS cancer (glio/astro) U-118-MG 54.0
CNS cancer (neuro; met) SK-N-AS  27.0
CNS cancer (astro) SF-539        25.9
CNS cancer (astro) SNB-75        94.6
CNS cancer (glio) SNB-19         7.1
CNS cancer (glio) SF-295         68.8
Brain (Amygdala) Pool            6.4
Brain (cerebellum)               31.2
Brain (fetal)                    100.0
Brain (Hippocampus) Pool         13.3
Cerebral Cortex Pool             8.7
Brain (Substantia nigra) Pool    5.6
Brain (Thalamus) Pool            9.4
Brain (whole)                    9.5
Spinal Cord Pool                 14.3
Adrenal Gland                    8.1
Pituitary gland Pool             14.8
Salivary Gland                   4.2
Thyroid (female)                 2.9
Pancreatic ca. CAPAN2            5.4
Pancreas Pool                    1.9

[0779]

TABLE IC
Panel 4.1D
                                 Rel. Exp. (%)
                                 Ag7001, Run
Tissue Name                      282263186
Secondary Th1 act                11.2
Secondary Th2 act                22.8
Secondary Tr1 act                3.7
Secondary Th1 rest               4.1
Secondary Th2 rest               0.0
Secondary Tr1 rest               8.5
Primary Th1 act                  0.0
Primary Th2 act                  6.0
Primary Tr1 act                  15.3
Primary Th1 rest                 0.0
Primary Th2 rest                 0.0
Primary Tr1 rest                 0.0
CD45RA CD4 lymphocyte act        17.8
CD45RO CD4 lymphocyte act        21.0
CD8 lymphocyte act               3.4
Secondary CD8 lymphocyte rest    3.8
Secondary CD8 lymphocyte act     0.0
CD4 lymphocyte none              3.5
2ry Th1/Th2/Tr1_anti-CD95 CH11   0.0
LAK cells rest                   7.6
LAK cells IL-2                   12.6
LAK cells IL-2 + IL-12           0.0
LAK cells IL-2 + IFN gamma       0.0
LAK cells IL-2 + IL-18           5.6
LAK cells PMA/ionomycin          18.7
NK Cells IL-2 rest               33.4
Two Way MLR 3 day                0.0
Two Way MLR 5 day                0.0
Two Way MLR 7 day                3.6
PBMC rest                        1.5
PBMC PWM                         7.2
PBMC PHA-L                       5.1
Ramos (B cell) none              7.7
Ramos (B cell) ionomycin         3.4
B lymphocytes PWM                2.2
B lymphocytes CD40L and IL-4     3.3
EOL-1 dbcAMP                     0.0
EOL-1 dbcAMP PMA/ionomycin       0.0
Dendritic cells none             8.5
Dendritic cells LPS              3.2
Dendritic cells anti-CD40        6.5
Monocytes rest                   0.0
Monocytes LPS                    5.8
Macrophages rest                 0.0
Macrophages LPS                  9.0
HUVEC none                       2.9
HUVEC starved                    6.9
HUVEC IL-1beta                   8.3
HUVEC IFN gamma                  8.5
HUVEC TNF alpha + IFN gamma      3.0
HUVEC TNF alpha + IL4            0.0
HUVEC IL-11                      0.0
Lung Microvascular EC none       23.5
Lung Microvascular EC TNFalpha + IL-1beta 9.2
Microvascular Dermal EC none     0.0
Microsvasular Dermal EC TNFalpha + IL-1beta 0.0
Bronchial epithelium TNFalpha + IL1beta 21.5
Small airway epithelium none     20.3
Small airway epithelium TNFalpha + IL-1beta 100.0
Coronery artery SMC rest         20.0
Coronery artery SMC TNFalpha + IL-1beta 29.9
Astrocytes rest                  11.7
Astrocytes TNFalpha + IL-1beta   27.4
KU-812 (Basophil) rest           12.1
KU-812 (Basophil) PMA/ionomycin  8.1
CCD1106 (Keratinocytes) none     24.1
CCD1106 (Keratinocytes) TNFalpha + IL-1beta 8.4
Liver cirrhosis                  4.2
NCI-H292 none                    4.8
NCI-H292 IL-4                    9.0
NCI-H292 IL-9                    35.4
NCI-H292 IL-13                   3.1
NCI-H292 IFN gamma               6.2
HPAEC none                       0.0
HPAEC TNF alpha + IL-1 beta      3.9
Lung fibroblast none             5.1
Lung fibroblast TNF alpha + IL-1 beta 16.6
Lung fibroblast IL-4             7.1
Lung fibroblast IL-9             9.3
Lung fibroblast IL-13            2.6
Lung fibroblast IFN gamma        16.7
Dermal fibroblast CCD1070 rest   37.9
Dermal fibroblast CCD1070 TNF alpha 68.3
Dermal fibroblast CCD1070 IL-1 beta 38.7
Dermal fibroblast IFN gamma      11.9
Dermal fibroblast IL-4           11.6
Dermal Fibroblasts rest          11.2
Neutrophils TNFa + LPS           6.2
Neutrophils rest                 44.8
Colon                            0.0
Lung                             6.3
Thymus                           3.3
Kidney                           11.1

[0780] General_screening_panel_v1.6 Summary: Ag7001 Highest expression is seen in fetal brain (CT=32.3). This gene is prominently expressed in the cancer cell lines on this panel and may be involved in cellular growth and/or proliferation.

[0781] Panel 4.1D Summary: Ag7001 Highest expression is seen in TNF-a and IL-1b treated small airway epithelium (CT=33.8). Therefore, modulation of the expression or activity of the protein encoded by this gene through the application of small molecule therapeutics may be useful in the treatment of asthma, COPD, and emphysema.

[0782] J. CG137339-01: Epidermal Growth Factor Receptor Precursor-Like Gene

[0783] Expression of gene CG137339-01 was assessed using the primer-probe sets Ag1333 and Ag7280, described in Tables JA and JB. Results of the RTQ-PCR runs are shown in Tables JC, JD, JE, JF, JG, JH, JI, JJ and JK.

TABLE JA
Probe Name Ag1333
			Start	SEQ
Primers	Sequences	Length	Position	ID No
Forward	5′-ggactatgtccgggaacacaa-3′	21	2418	251
Probe	TET-5′-atattggctcccagtacct	30	2444	252
	gctcaactggt-3′-TAMRA
Reverse	5′-tcatgccctttgcgatctg-3′	19	2479	253

[0784]

TABLE JB
Probe Name Ag7280
			Start	SEQ
Primers	Sequences	Length	Position	ID No
Forward	5′-ctccataaatgctacgaatatt	28	1233	254
	aaacac-3′
Probe	TET-5′-ctccatcagtggcgatct	25	1275	255
	ccacatc-3′-TAMRA
Reverse	5′-gaaaactgaccacccctaaatg-3′	22	1310	256

[0785]

TABLE JC
Ardais Panel v.1.0
                        Rel. Exp. (%)
                        Ag1333, Run
Tissue Name             263526730
136799_Lung cancer(362) 6.3
136800_Lung NAT(363)    3.4
136813_Lung cancer(372) 11.2
136814_Lung NAT(373)    1.7
136815_Lung cancer(374) 0.0
136816_Lung NAT(375)    46.0
136791_Lung cancer(35A) 0.0
136795_Lung cancer(35E) 100.0
136797_Lung cancer(360) 3.9
136794_lung NAT(35D)    0.0
136818_Lung NAT(377)    2.5
136787_lung cancer(356) 1.5
136788_lung NAT(357)    5.3
136804_Lung cancer(369) 13.3
136805_Lung NAT(36A)    2.1
136806_Lung cancer(36B) 8.2
136807_Lung NAT(36C)    1.5
136789_lung cancer(358) 8.7
136802_Lung cancer(365) 12.9
136803_Lung cancer(368) 10.8
136811_Lung cancer(370) 1.8
136810_Lung NAT(36F)    16.2

[0786]

TABLE JD
General_screening_panel_v1.4
                                 Rel. Exp. (%)
                                 Ag1333, Run
Tissue Name                      208579660
Adipose                          8.7
Melanoma* Hs688(A).T             8.5
Melanoma* Hs688(B).T             9.3
Melanoma* M14                    2.5
Melanoma* LOXIMVI                19.3
Melanoma* SK-MEL-5               2.1
Squamous cell carcinoma SCC-4    96.6
Testis Pool                      4.4
Prostate ca.* (bone met) PC-3    52.5
Prostate Pool                    4.3
Placenta                         100.0
Uterus Pool                      3.0
Ovarian ca. OVCAR-3              17.4
Ovarian ca. SK-OV-3              38.7
Ovarian ca. OVCAR-4              11.5
Ovarian ca. OVCAR-5              50.0
Ovarian ca. IGROV-1              4.1
Ovarian ca. OVCAR-8              8.2
Ovary                            6.4
Breast ca. MCF-7                 0.1
Breast ca. MDA-MB-231            25.7
Breast ca. BT 549                36.3
Breast ca. T47D                  35.6
Breast ca. MDA-N                 0.1
Breast Pool                      7.7
Trachea                          13.3
Lung                             4.5
Fetal Lung                       14.9
Lung ca. NCI-N417                0.6
Lung ca. LX-1                    2.5
Lung ca. NCI-H146                0.0
Lung ca. SHP-77                  2.0
Lung ca. A549                    22.4
Lung ca. NCI-H526                0.0
Lung ca. NCI-H23                 3.5
Lung ca. NCI-H460                11.8
Lung ca. HOP-62                  4.7
Lung ca. NCI-H522                1.5
Liver                            11.1
Fetal Liver                      19.3
Liver ca. HepG2                  4.4
Kidney Pool                      12.2
Fetal Kidney                     4.9
Renal ca. 786-0                  45.7
Renal ca. A498                   42.0
Renal ca. ACHN                   59.0
Renal ca. UO-31                  47.3
Renal ca. TK-10                  50.7
Bladder                          9.4
Gastric ca. (liver met.) NCI-N87 29.1
Gastric ca. KATO III             26.4
Colon ca. SW-948                 3.6
Colon ca. SW480                  12.0
Colon ca.* (SW480 met) SW620     0.0
Colon ca. HT29                   5.2
Colon ca. HCT-116                15.1
Colon ca. CaCo-2                 14.5
Colon cancer tissue              5.6
Colon ca. SW1116                 13.3
Colon ca. Colo-205               1.4
Colon ca. SW-48                  0.5
Colon Pool                       11.3
Small Intestine Pool             5.2
Stomach Pool                     5.2
Bone Marrow Pool                 5.4
Fetal Heart                      1.1
Heart Pool                       3.8
Lymph Node Pool                  10.1
Fetal Skeletal Muscle            3.6
Skeletal Muscle Pool             4.0
Spleen Pool                      2.1
Thymus Pool                      9.5
CNS cancer (glio/astro) U87-MG   33.2
CNS cancer (glio/astro) U-118-MG 37.6
CNS cancer (neuro; met) SK-N-AS  22.4
CNS cancer (astro) SF-539        7.5
CNS cancer (astro) SNB-75        11.2
CNS cancer (glio) SNB-19         3.9
CNS cancer (glio) SF-295         9.2
Brain (Amygdala) Pool            1.3
Brain (cerebellum)               6.6
Brain (fetal)                    6.6
Brain (Hippocampus) Pool         3.3
Cerebral Cortex Pool             3.0
Brain (Substantia nigra) Pool    2.6
Brain (Thalamus) Pool            3.1
Brain (whole)                    4.6
Spinal Cord Pool                 2.2
Adrenal Gland                    6.9
Pituitary gland Pool             0.4
Salivary Gland                   8.3
Thyroid (female)                 3.5
Pancreatic ca. CAPAN2            27.9
Pancreas Pool                    12.9

[0787]

TABLE JE
HASS Panel v1.0
		Rel. Exp. (%)	Rel. Exp. (%)
		Ag1333, Run	Ag1333, Run
	Tissue Name	247736608	248469481
	MCF-7 C1	0.0	0.0
	MCF-7 C2	0.0	0.0
	MCF-7 C3	0.0	0.0
	MCF-7 C4	0.0	0.0
	MCF-7 C5	0.0	0.0
	MCF-7 C6	0.1	0.1
	MCF-7 C7	0.4	0.4
	MCF-7 C9	0.5	0.3
	MCF-7 C10	0.0	0.0
	MCF-7 C11	0.0	0.0
	MCF-7 C12	0.1	0.0
	MCF-7 C13	0.4	0.3
	MCF-7 C15	0.2	0.1
	MCF-7 C16	0.2	0.2
	MCF-7 C17	0.1	0.1
	T24 D1	0.7	0.6
	T24 D2	0.9	0.8
	T24 D3	0.8	0.7
	T24 D4	1.4	1.3
	T24 D5	0.6	0.5
	T24 D6	2.4	1.8
	T24 D7	3.4	3.3
	T24 D9	1.3	1.1
	T24 D10	0.6	0.6
	T24 D11	0.3	0.3
	T24 D12	1.0	1.0
	T24 D13	2.0	1.8
	T24 D15	0.7	0.8
	T24 D16	0.4	0.4
	T24 D17	0.6	0.5
	CAPaN B1	2.7	2.3
	CAPaN B2	1.7	1.6
	CAPaN B3	0.5	0.4
	CAPaN B4	1.4	1.2
	CAPaN B5	1.2	1.0
	CAPaN B6	1.9	1.4
	CAPaN B7	1.3	1.4
	CAPaN B8	1.2	1.1
	CAPaN B9	2.2	2.4
	CAPaN B10	2.3	2.5
	CAPaN B11	1.7	1.4
	CAPaN B12	1.8	1.5
	CAPaN B13	2.0	1.5
	CAPaN B14	1.3	1.4
	CAPaN B15	2.8	2.5
	CAPaN B16	1.9	1.6
	CAPaN B17	2.5	2.0
	U87-MG F1 (B)	0.7	0.6
	U87-MG F2	0.4	0.4
	U87-MG F3	0.4	0.4
	U87-MG F4	0.7	0.7
	U87-MG F5	2.4	2.3
	U87-MG F6	1.2	1.3
	U87-MG F7	3.3	3.3
	U87-MG F8	2.0	1.9
	U87-MG F9	2.3	2.2
	U87-MG F10	1.5	1.4
	U87-MG F11	0.8	1.0
	U87-MG F12	1.9	1.6
	U87-MG F13	3.3	3.1
	U87-MG F14	2.6	2.6
	U87-MG F15	3.4	4.1
	U87-MG F16	1.9	1.7
	U87-MG F17	2.2	2.2
	LnCAP A1	0.9	0.8
	LnCAP A2	0.7	0.6
	LnCAP A3	0.2	0.2
	LnCAP A4	1.3	1.1
	LnCAP A5	0.6	0.5
	LnCAP A6	0.6	0.5
	LnCAP A7	5.2	4.9
	LnCAP A8	3.7	4.1
	LnCAP A9	3.2	3.2
	LnCAP A10	0.4	0.4
	LnCAP A11	0.5	0.5
	LnCAP A12	0.1	0.1
	LnCAP A13	0.6	0.5
	LnCAP A14	0.3	0.3
	LnCAP A15	0.6	0.5
	LnCAP A16	1.2	1.0
	LnCAP A17	0.9	0.4
	Primary Astrocytes	0.8	0.6
	Primary Renal Proximal	0.2	0.2
	Tubule Epithelial cell A2
	Primary melanocytes A5	0.1	0.1
	126443 - 341 medullo	0.0	0.0
	126444 - 487 medullo	0.1	0.1
	126445 - 425 medullo	0.0	0.0
	126446 - 690 medullo	0.2	0.2
	126447 - 54 adult glioma	3.8	3.1
	126448 - 245 adult glioma	100.0	100.0
	126449 - 317 adult glioma	42.0	35.8
	126450 - 212 glioma	1.2	0.8
	126451 - 456 glioma	61.6	52.9

[0788]

TABLE JF
Panel 1
                                 Rel. Exp. (%)
                                 Ag1333, Run
Tissue Name                      132087533
Endothelial cells                0.0
Endothelial cells (treated)      0.0
Pancreas                         0.2
Pancreatic ca. CAPAN 2           2.1
Adrenal gland                    1.0
Thyroid                          1.7
Salivary gland                   0.9
Pituitary gland                  0.0
Brain (fetal)                    0.5
Brain (whole)                    2.5
Brain (amygdala)                 0.0
Brain (cerebellum)               3.8
Brain (hippocampus)              1.6
Brain (substantia nigra)         0.7
Brain (thalamus)                 0.3
Brain (hypothalamus)             0.0
Spinal cord                      0.3
glio/astro U87-MG                2.6
glio/astro U-118-MG              2.1
astrocytoma SW1783               1.5
neuro*; met SK-N-AS              1.4
astrocytoma SF-539               0.7
astrocytoma SNB-75               0.4
glioma SNB-19                    1.5
glioma U251                      0.6
glioma SF-295                    0.9
Heart                            0.0
Skeletal muscle                  0.0
Bone marrow                      0.0
Thymus                           5.4
Spleen                           0.1
Lymph node                       0.3
Colon (ascending)                0.5
Stomach                          1.6
Small intestine                  0.5
Colon ca. SW480                  0.3
Colon ca.* SW620 (SW480 met)     0.0
Colon ca. HT29                   0.7
Colon ca. HCT-116                12.9
Colon ca. CaCo-2                 2.5
Colon ca. HCT-15                 1.3
Colon ca. HCC-2998               0.6
Gastric ca. * (liver met) NCI-N87 1.3
Bladder                          4.8
Trachea                          1.6
Kidney                           0.3
Kidney (fetal)                   0.7
Renal ca. 786-0                  6.7
Renal ca. A498                   8.0
Renal ca. RXF 393                5.4
Renal ca. ACHN                   8.8
Renal ca. UO-31                  5.0
Renal ca. TK-10                  22.4
Liver                            1.7
Liver (fetal)                    0.4
Liver ca. (hepatoblast) HepG2    0.1
Lung                             5.2
Lung (fetal)                     1.9
Lung ca. (small cell) LX-1       0.0
Lung ca. (small cell) NCI-H69    0.0
Lung ca. (s. cell var.) SHP-77   4.0
Lung ca. (large cell)NCI-H460    26.4
Lung ca. (non-sm. cell) A549     2.0
Lung ca. (non-s. cell) NCI-H23   0.1
Lung ca. (non-s. cell) HOP-62    0.0
Lung ca. (non-s. cl) NCI-H522    0.0
Lung ca. (squam.) SW 900         5.4
Lung ca. (squam.) NCI-H596       0.0
Mammary gland                    6.5
Breast ca.* (pl. ef) MCF-7       0.0
Breast ca.* (pl. ef) MDA-MB-231  4.2
Breast ca.* (pl. ef) T47D        0.4
Breast ca. BT-549                24.3
Breast ca. MDA-N                 0.0
Ovary                            1.6
Ovarian ca. OVCAR-3              2.0
Ovarian ca. OVCAR-4              1.7
Ovarian ca. OVCAR-5              5.2
Ovarian ca. OVCAR-8              3.4
Ovarian ca. IGROV-1              0.6
Ovarian ca. (ascites) SK-OV-3    3.2
Uterus                           1.6
Placenta                         22.7
Prostate                         1.4
Prostate ca.* (bone met) PC-3    100.0
Testis                           4.9
Melanoma Hs688(A).T              0.3
Melanoma* (met) Hs688(B).T       0.4
Melanoma UACC-62                 0.0
Melanoma M14                     0.0
Melanoma LOX IMVI                3.5
Melanoma* (met) SK-MEL-5         0.1
Melanoma SK-MEL-28               0.0

[0789]

TABLE JG
Panel 1.2
	Rel. Exp. (%)	Rel. Exp. (%)
	Ag1333, Run	Ag1333, Run
Tissue Name	133088120	133705801
Endothelial cells	0.7	0.9
Heart (Fetal)	1.3	1.3
Pancreas	0.7	0.8
Pancreatic ca. CAPAN2	8.8	7.6
Adrenal Gland	8.6	17.8
Thyroid	3.4	2.9
Salivary gland	10.7	11.5
Pituitary gland	1.3	1.3
Brain (fetal)	2.0	2.3
Brain (whole)	3.6	4.3
Brain (amygdala)	2.3	2.9
Brain (cerebellum)	2.4	2.4
Brain (hippocampus)	3.8	3.9
Brain (thalamus)	1.4	1.7
Cerebral Cortex	22.1	24.7
Spinal cord	1.2	2.3
glio/astro U87-MG	12.5	12.0
glio/astro U-118-MG	9.3	10.0
astrocytoma SW1783	5.4	2.6
neuro*; met SK-N-AS	9.9	18.0
astrocytoma SF-539	2.8	2.1
astrocytoma SNB-75	0.7	0.5
glioma SNB-19	7.3	6.0
glioma U251	3.8	3.5
glioma SF-295	3.3	3.1
Heart	9.9	12.7
Skeletal Muscle	3.4	3.5
Bone marrow	0.1	0.1
Thymus	2.5	2.0
Spleen	1.0	1.2
Lymph node	1.5	1.6
Colorectal Tissue	3.1	2.8
Stomach	8.2	8.1
Small intestine	2.4	3.1
Colon ca. SW480	4.8	5.1
Colon ca.* SW620 (SW480 met)	0.0	0.0
Colon ca. HT29	5.1	4.7
Colon ca. HCT-116	2.5	2.9
Colon ca. CaCo-2	2.3	2.9
Colon ca. Tissue (ODO3866)	2.7	3.0
Colon ca. HCC-2998	3.2	3.0
Gastric ca.* (liver met) NCI-N87	10.7	9.6
Bladder	15.1	17.0
Trachea	6.4	7.3
Kidney	2.5	3.4
Kidney (fetal)	5.6	6.3
Renal ca. 786-0	14.6	14.0
Renal ca. A498	40.9	41.5
Renal ca. RXF 393	22.1	16.4
Renal ca. ACHN	29.9	24.5
Renal ca. UO-31	18.4	13.4
Renal ca. TK-10	20.2	17.8
Liver	6.3	7.8
Liver (fetal)	5.2	5.7
Liver ca. (hepatoblast) HepG2	3.0	2.7
Lung	3.5	4.7
Lung (fetal)	4.3	4.9
Lung ca. (small cell) LX-1	1.2	1.1
Lung ca. (small cell) NCI-H69	0.0	0.0
Lung ca. (s. cell var.) SHP-77	0.5	0.4
Lung ca. (large cell)NCI-H460	38.4	25.7
Lung ca. (non-sm. cell) A549	6.9	6.1
Lung ca. (non-s. cell) NCI-H23	1.4	1.1
Lung ca. (non-s. cell) HOP-62	8.2	6.5
Lung ca. (non-s. cl) NCI-H522	2.6	2.7
Lung ca. (squam.) SW 900	12.2	11.4
Lung ca. (squam.) NCI-H596	0.0	0.0
Mammary gland	13.9	13.0
Breast ca.* (pl. ef) MCF-7	0.0	0.0
Breast ca.* (pl. ef) MDA-MB-231	12.3	10.7
Breast ca.* (pl. ef) T47D	1.2	1.5
Breast ca. BT-549	26.2	24.8
Breast ca. MDA-N	0.0	0.1
Ovary	11.3	11.9
Ovarian ca. OVCAR-3	8.5	8.4
Ovarian ca. OVCAR-4	19.3	16.4
Ovarian ca. OVCAR-5	24.3	0.1
Ovarian ca. OVCAR-8	22.7	22.2
Ovarian ca. IGROV-1	6.0	6.7
Ovarian ca. (ascites) SK-OV-3	23.0	20.7
Uterus	3.7	4.8
Placenta	100.0	100.0
Prostate	6.1	5.1
Prostate ca.* (bone met) PC-3	64.6	50.7
Testis	1.5	1.5
Melanoma Hs688(A).T	2.2	2.0
Melanoma* (met) Hs688(B).T	0.9	1.2
Melanoma UACC-62	1.1	1.2
Melanoma M14	0.3	0.4
Melanoma LOX IMVI	2.5	2.0
Melanoma* (met) SK-MEL-5	1.2	1.1

[0790]

TABLE JH
Panel 1.3D
                                 Rel. Exp. (%)
                                 Ag1333, Run
Tissue Name                      146087249
Liver adenocarcinoma             69.3
Pancreas                         1.2
Pancreatic ca. CAPAN 2           22.4
Adrenal gland                    3.6
Thyroid                          3.8
Salivary gland                   3.4
Pituitary gland                  0.5
Brain (fetal)                    2.0
Brain (whole)                    3.3
Brain (amygdala)                 3.0
Brain (cerebellum)               1.2
Brain (hippocampus)              3.8
Brain (substantia nigra)         0.5
Brain (thalamus)                 1.7
Cerebral Cortex                  36.9
Spinal cord                      2.5
glio/astro U87-MG                49.0
glio/astro U-118-MG              67.8
astrocytoma SW1783               37.4
neuro*; met SK-N-AS              36.9
astrocytoma SF-539               14.0
astrocytoma SNB-75               34.6
glioma SNB-19                    11.3
glioma U251                      10.2
glioma SF-295                    12.9
Heart (fetal)                    7.0
Heart                            1.7
Skeletal muscle (fetal)          100.0
Skeletal muscle                  2.3
Bone marrow                      0.1
Thymus                           2.8
Spleen                           1.3
Lymph node                       2.4
Colorectal                       12.8
Stomach                          5.5
Small intestine                  2.0
Colon ca. SW480                  30.6
Colon ca.* SW620(SW480 met)      0.0
Colon ca. HT29                   6.9
Colon ca. HCT-116                11.8
Colon ca. CaCo-2                 20.7
Colon ca. tissue(ODO3866)        11.0
Colon ca. HCC-2998               7.0
Gastric ca.* (liver met) NCI-N87 52.1
Bladder                          9.9
Trachea                          9.5
Kidney                           1.9
Kidney (fetal)                   3.4
Renal ca. 786-0                  53.6
Renal ca. A498                   84.1
Renal ca. RXF 393                21.3
Renal ca. ACHN                   78.5
Renal ca. UO-31                  50.3
Renal ca. TK-10                  43.5
Liver                            1.8
Liver (fetal)                    3.6
Liver ca. (hepatoblast) HepG2    5.6
Lung                             4.5
Lung (fetal)                     6.9
Lung ca. (small cell) LX-1       2.9
Lung ca. (small cell) NCI-H69    0.0
Lung ca. (s. cell var.) SHP-77   3.5
Lung ca. (large cell)NCI-H460    4.7
Lung ca. (non-sm. cell) A549     12.5
Lung ca. (non-s. cell) NCI-H23   3.3
Lung ca. (non-s. cell) HOP-62    5.9
Lung ca. (non-s. cl) NCI-H522    1.8
Lung ca. (squam.) SW 900         15.4
Lung ca. (squam.) NCI-H596       0.0
Mammary gland                    15.5
Breast ca.* (pl. ef) MCF-7       0.2
Breast ca.* (pl. ef) MDA-MB-231  89.5
Breast ca.* (pl. ef) T47D        2.6
Breast ca. BT-549                66.0
Breast ca. MDA-N                 0.2
Ovary                            43.5
Ovarian ca. OVCAR-3              18.3
Ovarian ca. OVCAR-4              7.3
Ovarian ca. OVCAR-5              54.3
Ovarian ca. OVCAR-8              37.1
Ovarian ca. IGROV-1              5.7
Ovarian ca.* (ascites) SK-OV-3   41.2
Uterus                           3.8
Placenta                         95.3
Prostate                         4.7
Prostate ca.* (bone met)PC-3     32.1
Testis                           2.5
Melanoma Hs688(A).T              17.8
Melanoma* (met) Hs688(B).T       24.3
Melanoma UACC-62                 0.3
Melanoma M14                     0.6
Melanoma LOX IMVI                4.4
Melanoma* (met) SK-MEL-5         1.9
Adipose                          10.7

[0791]

TABLE JI
Panel 2.2
	Rel. Exp. (%)	Rel. Exp. (%)
	Ag1333, Run	Ag1333, Run
Tissue Name	174923444	184372565
Normal Colon	15.2	15.2
Colon cancer (OD06064)	73.2	29.1
Colon Margin (OD06064)	29.7	0.0
Colon cancer (OD06159)	6.7	6.6
Colon Margin (OD06159)	37.1	18.6
Colon cancer (OD06297-04)	7.7	9.5
Colon Margin (OD06297-05)	52.5	23.0
CC Gr.2 ascend colon	11.1	10.3
(ODO3921)
CC Margin (ODO3921)	7.3	5.0
Colon cancer metastasis	2.3	1.7
(OD06104)
Lung Margin (OD06104)	5.1	7.1
Colon mets to lung	9.7	5.3
(OD04451-01)
Lung Margin (OD04451-02)	32.3	10.4
Normal Prostate	14.1	17.7
Prostate Cancer (OD04410)	6.3	11.9
Prostate Margin (OD04410)	11.6	30.6
Normal Ovary	27.4	16.3
Ovarian cancer (OD06283-03)	10.2	7.4
Ovarian Margin (OD06283-07)	6.7	4.1
Ovarian Cancer 064008	17.1	22.4
Ovarian cancer (OD06145)	15.3	9.5
Ovarian Margin (OD06145)	19.5	12.4
Ovarian cancer (OD06455-03)	19.5	15.9
Ovarian Margin (OD06455-07)	20.2	0.0
Normal Lung	12.6	8.8
Invasive poor diff. lung	4.2	3.5
adeno (ODO4945-01
Lung Margin (ODO4945-03)	27.5	11.0
Lung Malignant Cancer	12.8	4.6
(OD03126)
Lung Margin (OD03126)	13.4	38.4
Lung Cancer (OD05014A)	14.1	40.9
Lung Margin (OD05014B)	33.7	15.0
Lung cancer (OD06081)	21.8	14.2
Lung Margin (OD06081)	25.3	12.4
Lung Cancer (OD04237-01)	5.6	2.8
Lung Margin (OD04237-02)	25.9	15.4
Ocular Melanoma Metastasis	0.9	1.4
Ocular Melanoma Margin	29.7	29.1
(Liver)
Melanoma Metastasis	0.0	0.1
Melanoma Margin (Lung)	40.3	27.5
Normal Kidney	9.2	10.4
Kidney Ca, Nuclear	33.4	22.8
grade 2 (OD04338)
Kidney Margin (OD04338)	21.2	74.7
Kidney Ca Nuclear	18.2	12.2
grade 1/2 (OD04339)
Kidney Margin (OD04339)	16.7	13.5
Kidney Ca, Clear cell	45.1	46.3
type (OD04340)
Kidney Margin (OD04340)	17.7	8.7
Kidney Ca, Nuclear	2.1	3.3
grade 3 (OD04348)
Kidney Margin (OD04348)	67.8	14.0
Kidney malignant cancer	13.5	9.5
(OD06204B)
Kidney normal adjacent	13.8	11.3
tissue (OD06204E)
Kidney Cancer (OD04450-01)	72.7	35.8
Kidney Margin (OD04450-03)	21.3	29.5
Kidney Cancer 8120613	10.0	14.9
Kidney Margin 8120614	20.6	12.2
Kidney Cancer 9010320	10.4	12.2
Kidney Margin 9010321	16.2	9.0
Kidney Cancer 8120607	43.5	28.1
Kidney Margin 8120608	4.7	6.3
Normal Uterus	45.4	21.0
Uterine Cancer 064011	7.9	12.5
Normal Thyroid	2.8	6.9
Thyroid Cancer 064010	21.2	38.4
Thyroid Cancer A302152	20.4	24.3
Thyroid Margin A302153	6.9	16.4
Normal Breast	50.7	25.5
Breast Cancer (OD04566)	4.3	0.8
Breast Cancer 1024	17.0	13.4
Breast Cancer (OD04590-01)	5.8	0.0
Breast Cancer Mets (OD04590-03)	12.6	8.5
Breast Cancer Metastasis	2.3	2.6
(OD04655-05)
Breast Cancer 064006	7.7	6.0
Breast Cancer 9100266	5.6	5.6
Breast Margin 9100265	14.2	8.1
Breast Cancer A209073	7.5	6.8
Breast Margin A2090734	27.0	27.4
Breast cancer (OD06083)	19.3	7.6
Breast cancer node	5.0	7.5
metastasis (OD06083)
Normal Liver	55.5	58.2
Liver Cancer 1026	13.3	14.1
Liver Cancer 1025	100.0	100.0
Liver Cancer 6004-T	54.0	49.7
Liver Tissue 6004-N	17.8	14.0
Liver Cancer 6005-T	27.4	16.0
Liver Tissue 6005-N	73.7	39.5
Liver Cancer 064003	35.6	16.0
Normal Bladder	17.3	19.5
Bladder Cancer 1023	4.5	4.1
Bladder Cancer A302173	29.7	19.5
Normal Stomach	36.3	31.0
Gastric Cancer 9060397	5.8	7.3
Stomach Margin 9060396	7.4	6.4
Gastric Cancer 9060395	14.4	11.5
Stomach Margin 9060394	30.1	15.2
Gastric Cancer 064005	9.5	10.8

[0792]

TABLE JJ
Panel 4.1D
		Rel. Exp. (%)	Rel. Exp. (%)
		Ag1333, Run	Ag7280, Run
	Tissue Name	268700632	296559388
	Secondary Th1 act	0.0	0.0
	Secondary Th2 act	0.0	0.0
	Secondary Tr1 act	0.0	0.0
	Secondary Th1 rest	0.0	0.0
	Secondary Th2 rest	0.0	0.0
	Secondary Tr1 rest	0.0	0.0
	Primary Th1 act	0.0	0.0
	Primary Th2 act	0.0	0.0
	Primary Tr1 act	0.0	0.0
	Primary Th1 rest	0.0	0.0
	Primary Th2 rest	0.0	0.0
	Primary Tr1 rest	0.0	0.0
	CD45RA CD4	19.1	0.0
	lymphocyte act
	CD45RO CD4	0.0	0.0
	lymphocyte act
	CD8 lymphocyte act	0.0	0.0
	Secondary CD8	0.0	0.0
	lymphocyte rest
	Secondary CD8	0.0	0.0
	lymphocyte act
	CD4 lymphocyte none	0.0	0.0
	2ry	0.0	0.0
	Th1/Th2/Tr1_anti-
	CD95 CH11
	LAK cells rest	0.0	0.0
	LAK cells IL-2	0.0	0.0
	LAK cells	0.0	0.0
	IL-2 + IL-12
	LAK cells IL-2 + IFN	0.0	0.0
	gamma
	LAK cells IL-2 + IL-18	0.0	0.0
	LAK cells	0.0	0.0
	PMA/ionomycin
	NK Cells IL-2 rest	0.0	0.0
	Two Way MLR 3 day	0.0	0.0
	Two Way MLR 5 day	0.0	0.0
	Two Way MLR 7 day	0.0	0.0
	PBMC rest	0.0	0.0
	PBMC PWM	0.0	0.0
	PBMC PHA-L	0.0	0.0
	Ramos (B cell) none	0.2	0.0
	Ramos (B cell)	0.9	0.0
	ionomycin
	B lymphocytes PWM	0.0	0.0
	B lymphocytes	0.0	0.0
	CD40L and IL-4
	EOL-1 dbcAMP	0.0	0.0
	EOL-1 dbcAMP	0.0	0.0
	PMA/ionomycin
	Dendritic cells none	0.0	0.0
	Dendritic cells LPS	0.0	0.0
	Dendritic cells	0.0	0.0
	anti-CD40
	Monocytes rest	0.0	0.0
	Monocytes LPS	0.0	0.0
	Macrophages rest	0.0	0.0
	Macrophages LPS	0.0	0.0
	HUVEC none	1.5	0.0
	HUVEC starved	1.6	0.0
	HUVEC IL-1beta	1.7	0.0
	HUVEC IFN gamma	1.3	0.0
	HUVEC TNF alpha +	0.8	8.2
	IFN gamma
	HUVEC TNF alpha + IL4	1.3	0.0
	HUVEC IL-11	0.5	0.0
	Lung Microvascular	5.1	14.5
	EC none
	Lung Microvascular	4.1	0.0
	EC TNFalpha +
	IL-1beta
	Microvascular Dermal	1.0	0.0
	EC none
	Microsvasular Dermal	1.5	0.0
	EC TNFalpha +
	IL-1beta
	Bronchial epithelium	80.7	26.6
	TNFalpha + IL1beta
	Small airway	21.3	0.0
	epithelium none
	Small airway	80.7	66.0
	epithelium TNFalpha +
	IL-1beta
	Coronery artery SMC	21.8	8.0
	rest
	Coronery artery SMC	26.4	11.0
	TNFalpha + IL-1beta
	Astrocytes rest	1.4	0.0
	Astrocytes TNFalpha +	3.4	0.0
	IL-1beta
	KU-812 (Basophil)	0.0	0.0
	rest
	KU-812 (Basophil)	0.1	0.0
	PMA/ionomycin
	CCD1106	90.8	100.0
	(Keratinocytes) none
	CCD1106	54.3	50.0
	(Keratinocytes)
	TNFalpha + IL-1beta
	Liver cirrhosis	10.1	0.0
	NCI-H292 none	48.0	46.3
	NCI-H292 IL-4	62.4	53.6
	NCI-H292 IL-9	100.0	24.7
	NCI-H292 IL-13	62.0	47.3
	NCI-H292 IFN gamma	23.2	31.2
	HPAEC none	0.7	7.6
	HPAEC TNF alpha +	6.5	0.0
	IL-1 beta
	Lung fibroblast none	50.3	11.0
	Lung fibroblast TNF	29.9	31.0
	alpha + IL-1 beta
	Lung fibroblast IL-4	17.6	17.7
	Lung fibroblast IL-9	36.9	0.0
	Lung fibroblast IL-13	10.9	0.0
	Lung fibroblast IFN	28.3	0.0
	gamma
	Dermal fibroblast	31.6	0.0
	CCD1070 rest
	Dermal fibroblast	52.9	10.1
	CCD1070 TNF alpha
	Dermal fibroblast	29.5	18.2
	CCD1070 IL-1 beta
	Dermal fibroblast IFN	20.2	48.6
	gamma
	Dermal fibroblast IL-4	95.9	35.4
	Dermal Fibroblasts rest	58.2	15.1
	Neutrophils	0.0	0.0
	TNFa + LPS
	Neutrophils rest	0.0	0.0
	Colon	1.1	0.0
	Lung	1.0	0.0
	Thymus	2.1	0.0
	Kidney	7.9	0.0

[0793]

TABLE JK
general oncology screening panel_v_2.4
		Rel. Exp. (%)	Rel. Exp. (%)
		Ag1333, Run	Ag1333, Run
	Tissue Name	258052150	258689219
	Colon cancer 1	6.5	9.4
	Colon NAT 1	3.0	2.3
	Colon cancer 2	9.6	8.4
	Colon NAT 2	4.1	3.8
	Colon cancer 3	16.7	16.3
	Colon NAT 3	10.3	12.3
	Colon malignant cancer 4	11.7	11.0
	Colon NAT 4	5.1	4.2
	Lung cancer 1	10.5	13.0
	Lung NAT 1	1.2	1.1
	Lung cancer 2	45.1	45.1
	Lung NAT 2	1.8	1.9
	Squamous cell carcinoma 3	20.2	20.7
	Lung NAT 3	0.6	0.5
	Metastatic melanoma 1	8.6	11.1
	Melanoma 2	6.7	6.9
	Melanoma 3	4.7	6.4
	Metastatic melanoma 4	29.1	27.5
	Metastatic melanoma 5	32.1	25.9
	Bladder cancer 1	0.2	0.5
	Bladder NAT 1	0.0	0.0
	Bladder cancer 2	2.5	3.1
	Bladder NAT 2	0.1	0.2
	Bladder NAT 3	0.3	0.7
	Bladder NAT 4	3.3	3.1
	Prostate adenocarcinoma 1	6.3	11.3
	Prostate adenocarcinoma 2	3.1	1.2
	Prostate adenocarcinoma 3	10.4	9.4
	Prostate adenocarcinoma 4	8.5	8.1
	Prostate NAT 5	2.7	2.8
	Prostate adenocarcinoma 6	3.9	3.5
	Prostate adenocarcinoma 7	2.7	3.9
	Prostate adenocarcinoma 8	1.7	1.3
	Prostate adenocarcinoma 9	9.2	10.7
	Prostate NAT 10	1.1	1.5
	Kidney cancer 1	18.4	21.0
	Kidney NAT 1	3.8	3.6
	Kidney cancer 2	100.0	100.0
	Kidney NAT 2	8.5	8.6
	Kidney cancer 3	20.0	21.3
	Kidney NAT 3	2.2	2.8
	Kidney cancer 4	16.8	16.4
	Kidney NAT 4	2.9	3.4

[0794] Ardais Panel v.1.0 Summary: Ag1333 Highest expression is seen in a lung cancer sample (CT=20.13). In addition, this gene is overexpressed in lung cancer when compared to expression in the NAT. Thus, expression of this gene could be used to differentiate between this sample and other samples on this panel and as a marker of lung cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of lung cancer.

[0795] General_screening_panel_v1.4 Summary: Ag1333 Highest expression of this gene is seen in placenta (CT=21.4). 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. 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.

[0796] 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.

[0797] 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.

[0798] HASS Panel v1.0 Summary: Ag1333 Two experiments with same probe and primer sets are in excellent agreement with highest expression of this gene seen in adult glioma samples (CTs=20.9). In addition, the expression of this gene is induced in LnCAP, T24 and MCF7 cells by a reduction of oxygen concentration compared to the normally low level of gene expression seen in these cell lines. This suggests that expression of this gene may also be increased in hypoxic regions of bladder, breast and prostate cancers.

[0799] This gene is also expressed at a low level in medulloblastoma samples and at a moderate level in glioma samples. It may thus be used as marker and modulation of the protein encoded by this gene through the use of antibodies or small molecule drugs may be used for therapy.

[0800] Panel 1 Summary: AG1333 Highest expression is seen in a prostate cancer cell line (CT=19). In addition, this gene is expressed in many samples on this panel. Please see Panel 1.4 for discussion of utility of this gene.

[0801] Panel 1.2 Summary: Ag1333 Two experiments with the same probe and primer produce results that are in excellent agreement, with highest expression in placenta (CTs=24-25). The results in this panel are consistent with Panel 1.4. Please see that panel for further discussion of utility of this gene.

[0802] Panel 1.3D Summary: Ag1333 Highest expression of this gene is seen in skeletal muscle (CT=26). In addition, this gene is expressed at much higher levels in fetal skeletal muscle when compared to adult skeletal muscle (CT=31). This observation suggests that expression of this gene can be used to distinguish fetal from adult skeletal muscle. In addition, the relative overexpression of this gene in fetal skeletal muscle suggests that the protein product may enhance muscular growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of muscle related diseases. More specifically, treatment of weak or dystrophic muscle with the protein encoded by this gene could restore muscle mass or function.

[0803] Overall, expression in this panel is consistent with expression on panel 1.4, with prominenet expression in the cancer cell lines on this panel. Please see Panel 1.4 for discussion of utility of this gene.

[0804] Panel 2.2 Summary: Ag1333 Two experiments with the same probe and primer produce results that are in excellent agreement. Highest expression of this gene is seen in a liver cancer (CTs=25-29). This gene is widely expressed in this panel, with higher levels of expression in kidney cancer than in the NAT, consistent with Panel 2.4. Please see that panel for discussion of utility of this gene.

[0805] Panel 4.1D Summary: Ag1333 Expression of this gene is highest in IL-9 treated NCI—H292 cells (CT=26.5). Expression of this gene appears to be associated with clusters of samples derived from treated and untreated keratinoyctes, lung and dermal fibroblasts, and HPAECS. Thus, this gene may be involved in inflammatory conditions of the lung and/or skin.

[0806] general oncology screening panel_v—2.4 Summary: Ag1333 Two experiments with the same probe and primer set produce results that are in excellent agreement. Highest expression is seen in a sample derived from kidney cancer (CTs=26). In addition, this gene is overexpressed in kidney and lung cancers when compared to expression in the normal adjacent tissue. Prominent expression is also detected in melanoma. Thus, expression of this gene could be used as a marker of these cancers and modulation of the expression or function may be useful in their treatment.

[0807] K. CG138130-01: cGMP-Stimulated 3′,5′-cyclic Nucleotide Phosphodiesterase-Like Gene

[0808] Expression of gene CG138130-01 was assessed using the primer-probe set Ag4203, described in Table KA. Results of the RTQ-PCR runs are shown in Table KB.

TABLE KA
Probe Name Ag4203
				SEQ
			Start	ID
Primers	Sequences	Length	Position	No
Forward	5′-caccagatctttgctcctttc-3′	21	3234	257
Probe	TET-5′-accctttgggtctccagg	26	3270	258
	atcctcat-3′-TAMRA
Reverse	5′-gctcactcagatgtctcacctt-3′	22	3304	259

[0809]

TABLE KB
Panel 5 Islet
                                 Rel. Exp. (%)
                                 Ag4203, Run
Tissue Name                      174269008
97457_Patient-02go_adipose       59.0
97476_Patient-07sk_skeletal muscle 33.2
97477_Patient-07ut_uterus        39.0
97478_Patient-07pl_placenta      10.7
99167_Bayer Patient 1            19.1
97482_Patient-08ut_uterus        15.8
97483_Patient-08pl_placenta      4.5
97486_Patient-09sk_skeletal muscle 5.7
97487_Patient-09ut_uterus        23.0
97488_Patient-09pl_placenta      9.4
97492_Patient-10ut_uterus        23.0
97493_Patient-10pl_placenta      25.5
97495_Patient-11go_adipose       17.1
97496_Patient-11sk_skeletal muscle 12.9
97497_Patient-11ut_uterus        42.9
97498_Patient-11pl_placenta      2.1
97500_Patient-12go_adipose       100.0
97501_Patient-12sk_skeletal muscle 46.3
97502_Patient-12ut_uterus        35.6
97503_Patient-12pl_placenta      3.3
94721_Donor 2 U - A_Mesenchymal Stem Cells 0.0
94722_Donor 2 U - B_Mesenchymal Stem Cells 0.0
94723_Donor 2 U - C_Mesenchymal Stem Cells 0.0
94709_Donor 2 AM - A_adipose     0.0
94710_Donor 2 AM - B_adipose     0.0
94711_Donor 2 AM - C_adipose     0.0
94712_Donor 2 AD - A_adipose     0.0
94713_Donor 2 AD - B_adipose     0.0
94714_Donor 2 AD - C_adipose     0.0
94742_Donor 3 U - A_Mesenchymal Stem Cells 1.3
94743_Donor 3 U - B_Mesenchymal Stem Cells 0.0
94730_Donor 3 AM - A_adipose     0.0
94731_Donor 3 AM - B_adipose     0.0
94732_Donor 3 AM - C_adipose     0.9
94733_Donor 3 AD - A_adipose     0.0
94734_Donor 3 AD - B_adipose     0.0
94735_Donor 3 AD - C_adipose     0.0
77138_Liver_HepG2untreated       0.0
73556_Heart_Cardiac stromal cells (primary) 77.9
81735_Small Intestine            22.2
72409_Kidney_Proximal Convoluted Tubule 0.0
82685_Small intestine_Duodenum   1.4
90650_Adrenal_Adrenocortical adenoma 6.4
72410_Kidney_HRCE                1.5
72411_Kidney_HRE                 0.0
73139_Uterus_Uterine smooth muscle cells 1.4

[0810] Panel 5 Islet Summary: Ag4203 Highest expression is seen in adipose (CT=32), with low but significant expression seen in other metabolic tissues, including skeletal muscle and placenta. Thus, this gene product may be involved in the pathogenesis and/or treatment of metabolic disease, including obesity and diabetes.

[0811] L. CG138372-02: MALEYLACETOACETATE ISOMERASE

[0812]

[0813] Expression of full-length physical clone CG138372-02 was assessed using the primer-probe set Ag5913, described in Table LA. Results of the RTQ-PCR runs are shown in Tables LB, LC and LD.

TABLE LA
Probe Name Ag5913
				SEQ
			Start	ID
Primers	Sequences	Length	Position	No
Forward	5′-gccaacagttttctaaggactt	23	145	260
	c-3′
Probe	TET-5′-attccatcaatcttcagg	26	192	261
	gttggcac-3′-TAMRA
Reverse	5′-acagacaggtttgactggtgaa	23	222	262
	t-3′

[0814]

TABLE LB
General_screening_panel_v1.5
	Rel. Exp. (%)	Rel. Exp. (%)
	Ag5913, Run	Ag5913, Run
Tissue Name	247608924	259048761
Adipose	1.8	2.4
Melanoma* Hs688(A).T	3.7	4.6
Melanoma* Hs688(B).T	3.7	3.9
Melanoma* M14	12.6	13.5
Melanoma* LOXIMVI	7.3	4.8
Melanoma* SK-MEL-5	44.8	33.2
Squamous cell carcinoma SCC-4	7.4	6.2
Testis Pool	5.2	6.2
Prostate ca.* (bone met) PC-3	35.6	27.7
Prostate Pool	3.3	4.5
Placenta	2.5	2.5
Uterus Pool	0.7	1.2
Ovarian ca. OVCAR-3	18.8	21.2
Ovarian ca. SK-OV-3	8.1	9.0
Ovarian ca. OVCAR-4	7.2	10.7
Ovarian ca. OVCAR-5	75.3	68.3
Ovarian ca. IGROV-1	8.6	7.5
Ovarian ca. OVCAR-8	13.8	12.3
Ovary	1.1	2.6
Breast ca. MCF-7	40.3	36.9
Breast ca. MDA-MB-231	44.1	33.7
Breast ca. BT 549	13.2	10.4
Breast ca. T47D	14.4	14.7
Breast ca. MDA-N	14.8	14.5
Breast Pool	2.4	2.4
Trachea	4.0	4.2
Lung	0.9	0.2
Fetal Lung	2.0	3.4
Lung ca. NCI-N417	11.6	9.9
Lung ca. LX-1	40.1	45.4
Lung ca. NCI-H146	11.2	10.3
Lung ca. SHP-77	22.2	31.0
Lung ca. A549	27.0	29.1
Lung ca. NCI-H526	5.1	7.3
Lung ca. NCI-H23	13.6	11.2
Lung ca. NCI-H460	4.8	7.5
Lung ca. HOP-62	7.3	7.6
Lung ca. NCI-H522	9.2	11.7
Liver	19.1	21.9
Fetal Liver	16.5	7.3
Liver ca. HepG2	9.9	14.4
Kidney Pool	2.9	3.2
Fetal Kidney	3.4	2.4
Renal ca. 786-0	15.4	9.9
Renal ca. A498	4.1	4.7
Renal ca. ACHN	14.5	22.2
Renal ca. UO-31	9.7	12.9
Renal ca. TK-10	15.6	19.3
Bladder	4.0	4.4
Gastric ca. (liver met.) NCI-N87	13.2	16.8
Gastric ca. KATO III	41.8	41.5
Colon ca. SW-948	8.1	7.5
Colon ca. SW480	56.3	54.7
Colon ca.* (SW480 met) SW620	19.3	31.9
Colon ca. HT29	8.2	10.3
Colon ca. HCT-116	24.0	21.5
Colon ca. CaCo-2	19.6	12.6
Colon cancer tissue	5.8	7.6
Colon ca. SW1116	7.6	11.7
Colon ca. Colo-205	12.2	8.5
Colon ca. SW-48	7.0	9.2
Colon Pool	2.0	1.9
Small Intestine Pool	2.0	1.6
Stomach Pool	1.7	1.5
Bone Marrow Pool	1.4	1.1
Fetal Heart	1.4	1.3
Heart Pool	1.0	1.3
Lymph Node Pool	2.1	0.3
Fetal Skeletal Muscle	2.0	2.3
Skeletal Muscle Pool	13.5	14.9
Spleen Pool	1.9	5.6
Thymus Pool	4.2	3.5
CNS cancer (glio/astro) U87-MG	100.0	100.0
CNS cancer (glio/astro) U-118-MG	16.5	18.7
CNS cancer (neuro; met) SK-N-AS	19.2	19.9
CNS cancer (astro) SF-539	4.9	4.4
CNS cancer (astro) SNB-75	25.9	21.3
CNS cancer (glio) SNB-19	6.9	7.1
CNS cancer (glio) SF-295	8.0	10.4
Brain (Amygdala) Pool	3.2	2.2
Brain (cerebellum)	4.3	4.9
Brain (fetal)	0.8	1.1
Brain (Hippocampus) Pool	2.5	1.8
Cerebral Cortex Pool	1.6	2.8
Brain (Substantia nigra) Pool	3.5	1.7
Brain (Thalamus) Pool	2.3	4.4
Brain (whole)	5.7	3.3
Spinal Cord Pool	5.5	7.9
Adrenal Gland	5.6	4.5
Pituitary gland Pool	1.7	0.9
Salivary Gland	5.3	5.1
Thyroid (female)	4.1	3.4
Pancreatic ca. CAPAN2	28.5	29.5
Pancreas Pool	2.5	4.7

[0815]

TABLE LC
Panel 5 Islet
	Rel. Exp. (%)	Rel. Exp. (%)
	Ag5913, Run	Ag5913, Run
Tissue Name	247624441	259234351
97457_Patient-02go_adipose	47.6	23.0
97476_Patient-07sk_skeletal muscle	19.8	3.2
97477_Patient-07ut_uterus	0.0	8.5
97478_Patient-07pl_placenta	11.3	14.7
99167_Bayer Patient 1	90.8	43.2
97482_Patient-08ut_uterus	0.0	6.6
97483_Patient-08pl_placenta	11.0	18.0
97486_Patient-09sk_skeletal muscle	3.6	8.4
97487_Patient-09ut_uterus	12.2	6.3
97488_Patient-09pl_placenta	20.2	7.3
97492_Patient-10ut_uterus	3.4	2.5
97493_Patient-10pl_placenta	74.7	5.1
97495_Patient-11go_adipose	18.4	6.8
97496_Patient-11sk_skeletal muscle	65.5	18.7
97497_Patient-11ut_uterus	57.0	2.6
97498_Patient-11pl_placenta	16.4	10.2
97500_Patient-12go_adipose	59.5	32.1
97501_Patient-12sk_skeletal muscle	100.0	40.6
97502_Patient-12ut_uterus	5.3	8.9
97503_Patient-12pl_placenta	8.8	6.4
94721_Donor 2 U - A_Mesenchymal	37.6	24.8
Stem Cells
94722_Donor 2 U - B_Mesenchymal	11.2	23.3
Stem Cells
94723_Donor 2 U - C_Mesenchymal	33.9	4.8
Stem Cells
94709_Donor 2 AM - A_adipose	27.9	9.3
94710_Donor 2 AM - B_adipose	4.8	30.1
94711_Donor 2 AM - C_adipose	11.8	3.8
94712_Donor 2 AD - A_adipose	23.5	12.8
94713_Donor 2 AD - B_adipose	5.6	38.2
94714_Donor 2 AD - C_adipose	55.9	20.9
94742_Donor 3 U - A_Mesenchymal	12.2	11.2
Stem Cells
94743_Donor 3 U - B_Mesenchymal	23.3	10.3
Stem Cells
94730_Donor 3 AM - A_adipose	40.9	21.2
94731_Donor 3 AM - B_adipose	0.0	13.6
94732_Donor 3 AM - C_adipose	9.1	13.0
94733_Donor 3 AD - A_adipose	25.2	17.4
94734_Donor 3 AD - B_adipose	23.8	0.0
94735_Donor 3 AD - C_adipose	0.0	26.6
77138_Liver_HepG2untreated	65.5	100.0
73556_Heart_Cardiac stromal	40.1	19.3
cells (primary)
81735_Small Intestine	55.5	15.7
72409_Kidney_Proximal Convoluted	26.2	19.1
Tubule
82685_Small intestine_Duodenum	0.0	7.1
90650_Adrenal_Adrenocortical	30.6	16.4
adenoma
72410_Kidney_HRCE	95.9	53.6
72411_Kidney_HRE	26.4	43.8
73139_Uterus_Uterine smooth	0.0	8.5
muscle cells

[0816]

TABLE LD
general oncology screening panel_v_2.4
                          Rel. Exp. (%)
                          Ag5913, Run
Tissue Name               260316171
Colon cancer 1            15.1
Colon NAT 1               11.5
Colon cancer 2            8.7
Colon NAT 2               10.6
Colon cancer 3            21.3
Colon NAT 3               19.9
Colon malignant cancer 4  100.0
Colon NAT 4               10.4
Lung cancer 1             51.4
Lung NAT 1                0.0
Lung cancer 2             25.2
Lung NAT 2                0.0
Squamous cell carcinoma 3 20.6
Lung NAT 3                0.0
Metastatic melanoma 1     7.1
Melanoma 2                2.3
Melanoma 3                2.2
Metastatic melanoma 4     11.9
Metastatic melanoma 5     15.2
Bladder cancer 1          2.1
Bladder NAT 1             0.0
Bladder cancer 2          0.9
Bladder NAT 2             0.0
Bladder NAT 3             0.9
Bladder NAT 4             0.0
Prostate adenocarcinoma 1 3.1
Prostate adenocarcinoma 2 1.5
Prostate adenocarcinoma 3 22.1
Prostate adenocarcinoma 4 14.6
Prostate NAT 5            5.4
Prostate adenocarcinoma 6 4.7
Prostate adenocarcinoma 7 4.8
Prostate adenocarcinoma 8 3.6
Prostate adenocarcinoma 9 13.0
Prostate NAT 10           0.6
Kidney cancer 1           13.9
Kidney NAT 1              6.7
Kidney cancer 2           63.7
Kidney NAT 2              13.4
Kidney cancer 3           16.8
Kidney NAT 3              0.7
Kidney cancer 4           9.7
Kidney NAT 4              5.8

[0817] General_screening_panel_v1.5 Summary: Ag5913 Two experiments with the same probe and primer set produce results that are in excellent agreement. Highest expression is seen in a brain cancer cell line (CTs=30).

[0818] This gene is widely expressed in this panel, with moderate 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.

[0819] Among tissues with metabolic function, this gene is expressed at low but significant levels in adrenal gland, skeletal muscle, and adult and fetal 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.

[0820] Panel 5 Islet Summary: Ag5913 Low but significant expression is seen in a liver cell line and skeletal muscle.

[0821] general oncology screening panel_v—2.4 Summary: Ag5913 Highest expression is seen in a colon cancer (CT=32.5). In addition, this gene is overexpressed in colon, kidney, and lung cancers when compared to expression in the normal adjacent tissue. Thus, expression of this gene could be used as a marker of these cancers and modulation of the function of this gene product may be useful in the treatment of these cancers.

[0822] M. CG138461-01: Novel Intracellular Nitroreductase-Like Gene

[0823] Expression of gene CG138461-01 was assessed using the primer-probe set Ag4962, described in Table MA. Results of the RTQ-PCR runs are shown in Tables MB and MC.

TABLE MA
Probe Name Ag4962
				SEQ
			Start	ID
Primers	Sequences	Length	Position	No
Forward	5′-gggtcacagacctcaagaaac-	21	509	263
	3′
Probe	TET-5′-tggatactgcccctattt	27	557	264
	tgattctca-3′-TAMRA
Reverse	5′-gcgaaaccatgtacttgtttg-	21	588	265
	3′

[0824]

TABLE MB
General_screening_panel_v1.5
                                 Rel. Exp. (%)
                                 Ag4962, Run
Tissue Name                      228903674
Adipose                          0.1
Melanoma* Hs688(A).T             0.0
Melanoma* Hs688(B).T             0.0
Melanoma* M14                    0.0
Melanoma* LOXIMVI                0.0
Melanoma* SK-MEL-5               0.0
Squamous cell carcinoma SCC-4    0.0
Testis Pool                      0.1
Prostate ca.* (bone met) PC-3    0.0
Prostate Pool                    0.0
Placenta                         0.0
Uterus Pool                      0.0
Ovarian ca. OVCAR-3              0.0
Ovarian ca. SK-OV-3              0.0
Ovarian ca. OVCAR-4              0.0
Ovarian ca. OVCAR-5              0.2
Ovarian ca. IGROV-1              0.0
Ovarian ca. OVCAR-8              0.0
Ovary                            2.5
Breast ca. MCF-7                 0.0
Breast ca. MDA-MB-231            0.0
Breast ca. BT 549                0.0
Breast ca. T47D                  0.0
Breast ca. MDA-N                 0.0
Breast Pool                      0.0
Trachea                          0.6
Lung                             0.0
Fetal Lung                       0.4
Lung ca. NCI-N417                0.0
Lung ca. LX-1                    0.0
Lung ca. NCI-H146                0.0
Lung ca. SHP-77                  0.0
Lung ca. A549                    0.0
Lung ca. NCI-H526                0.0
Lung ca. NCI-H23                 0.0
Lung ca. NCI-H460                0.0
Lung ca. HOP-62                  0.0
Lung ca. NCI-H522                0.0
Liver                            1.7
Fetal Liver                      2.8
Liver ca. HepG2                  0.1
Kidney Pool                      0.0
Fetal Kidney                     0.4
Renal ca. 786-0                  0.0
Renal ca. A498                   0.0
Renal ca. ACHN                   0.0
Renal ca. UO-31                  0.0
Renal ca. TK-10                  0.0
Bladder                          1.7
Gastric ca. (liver met.) NCI-N87 0.2
Gastric ca. KATO III             3.3
Colon ca. SW-948                 0.9
Colon ca. SW480                  0.0
Colon ca.* (SW480 met) SW620     0.0
Colon ca. HT29                   0.2
Colon ca. HCT-116                0.0
Colon ca. CaCo-2                 6.6
Colon cancer tissue              2.3
Colon ca. SW1116                 0.0
Colon ca. Colo-205               0.8
Colon ca. SW-48                  3.0
Colon Pool                       0.0
Small Intestine Pool             0.0
Stomach Pool                     0.1
Bone Marrow Pool                 0.0
Fetal Heart                      0.0
Heart Pool                       0.0
Lymph Node Pool                  0.0
Fetal Skeletal Muscle            0.0
Skeletal Muscle Pool             0.0
Spleen Pool                      0.0
Thymus Pool                      0.0
CNS cancer (glio/astro) U87-MG   0.0
CNS cancer (glio/astro) U-118-MG 0.0
CNS cancer (neuro; met) SK-N-AS  0.0
CNS cancer (astro) SF-539        0.0
CNS cancer (astro) SNB-75        0.0
CNS cancer (glio) SNB-19         0.0
CNS cancer (glio) SF-295         0.1
Brain (Amygdala) Pool            0.0
Brain (cerebellum)               0.0
Brain (fetal)                    0.0
Brain (Hippocampus) Pool         0.0
Cerebral Cortex Pool             0.0
Brain (Substantia nigra) Pool    0.0
Brain (Thalamus) Pool            0.0
Brain (whole)                    0.1
Spinal Cord Pool                 0.0
Adrenal Gland                    0.0
Pituitary gland Pool             0.0
Salivary Gland                   0.2
Thyroid (female)                 100.0
Pancreatic ca. CAPAN2            0.0
Pancreas Pool                    0.1

[0825]

TABLE MC
Panel 4.1D
                                 Rel. Exp. (%)
                                 Ag4962, Run
Tissue Name                      223691582
Secondary Th1 act                0.0
Secondary Th2 act                0.0
Secondary Tr1 act                0.0
Secondary Th1 rest               0.0
Secondary Th2 rest               0.0
Secondary Tr1 rest               0.0
Primary Th1 act                  0.0
Primary Th2 act                  0.0
Primary Tr1 act                  0.0
Primary Th1 rest                 0.0
Primary Th2 rest                 0.0
Primary Tr1 rest                 0.0
CD45RA CD4 lymphocyte act        0.0
CD45RO CD4 lymphocyte act        0.0
CD8 lymphocyte act               0.0
Secondary CD8 lymphocyte rest    0.0
Secondary CD8 lymphocyte act     0.0
CD4 lymphocyte none              0.0
2ry Th1/Th2/Tr1_anti-CD95 CH11   0.0
LAK cells rest                   0.0
LAK cells IL-2                   0.0
LAK cells IL-2 + IL-12           0.0
LAK cells IL-2 + IFN gamma       0.0
LAK cells IL-2 + IL-18           0.0
LAK cells PMA/ionomycin          0.0
NK Cells IL-2 rest               0.0
Two Way MLR 3 day                0.0
Two Way MLR 5 day                0.0
Two Way MLR 7 day                0.0
PBMC rest                        0.0
PBMC PWM                         0.0
PBMC PHA-L                       0.0
Ramos (B cell) none              0.0
Ramos (B cell) ionomycin         0.0
B lymphocytes PWM                0.0
B lymphocytes CD40L and IL-4     0.0
EOL-1 dbcAMP                     0.0
EOL-1 dbcAMP PMA/ionomycin       0.0
Dendritic cells none             0.0
Dendritic cells LPS              0.0
Dendritic cells anti-CD40        0.0
Monocytes rest                   0.0
Monocytes LPS                    0.0
Macrophages rest                 0.0
Macrophages LPS                  0.0
HUVEC none                       0.0
HUVEC starved                    0.0
HUVEC IL-1beta                   0.0
HUVEC IFN gamma                  0.0
HUVEC TNF alpha + IFN gamma      0.0
HUVEC TNF alpha + IL4            0.0
HUVEC IL-11                      0.0
Lung Microvascular EC none       0.0
Lung Microvascular EC TNFalpha + 0.0
IL-1beta
Microvascular Dermal EC none     0.0
Microsvasular Dermal EC          0.0
TNFalpha + IL-1beta
Bronchial epithelium TNFalpha +  0.2
IL1beta
Small airway epithelium none     0.2
Small airway epithelium          0.6
TNFalpha + IL-1beta
Coronery artery SMC rest         0.0
Coronery artery SMC TNFalpha +   0.0
IL-1beta
Astrocytes rest                  0.0
Astrocytes TNFalpha + IL-1beta   0.2
KU-812 (Basophil) rest           0.0
KU-812 (Basophil) PMA/ionomycin  0.0
CCD1106 (Keratinocytes) none     0.0
CCD1106 (Keratinocytes)          0.0
TNFalpha + IL-1beta
Liver cirrhosis                  1.9
NCI-H292 none                    0.4
NCI-H292 IL-4                    0.4
NCI-H292 IL-9                    0.4
NCI-H292 IL-13                   0.0
NCI-H292 IFN gamma               0.1
HPAEC none                       0.0
HPAEC TNF alpha + IL-1 beta      0.0
Lung fibroblast none             0.0
Lung fibroblast TNF alpha + IL-1 0.0
beta
Lung fibroblast IL-4             0.0
Lung fibroblast IL-9             0.0
Lung fibroblast IL-13            0.0
Lung fibroblast IFN gamma        0.0
Dermal fibroblast CCD1070 rest   0.0
Dermal fibroblast CCD1070 TNF alpha 0.0
Dermal fibroblast CCD1070 IL-1   0.0
beta
Dermal fibroblast IFN gamma      0.0
Dermal fibroblast IL-4           0.0
Dermal Fibroblasts rest          0.0
Neutrophils TNFa + LPS           0.0
Neutrophils rest                 0.0
Colon                            13.2
Lung                             0.7
Thymus                           0.0
Kidney                           100.0

[0826] General_screening'panel'v1.5 Summary: Ag4962 Expression of this gene is restricted to the thyroid (CT=26.5). Thus, expression of this gene could be used to differentiate between this sample and other samples on this panel, and as a marker of thyroid tissue. Modulation of the expression or function of this protein may be useful in the treatment of thyroidopathies.

[0827] Panel 4.1D Summary: Ag4962 This gene is only expressed at detectable levels in the kidney (CT=30. 1). 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.

[0828] N. CG138529-01: SA PROTEIN (Medium-Chain Acyl-CoA Synthetase)-Like Gene

[0829] Expression of gene CG138529-01 was assessed using the primer-probe set Ag4963, described in Table NA. Results of the RTQ-PCR runs are shown in Tables NB, NC, ND and NE.

TABLE NA
Probe Name Ag4963
			Start	SEQ
Primers	Sequences	Length	Position	ID No
Forward	5′-aagatccaatggccatattctt-	22	757	266
	3′
Probe	TET-5′-caagggtacaacaggagc	26	782	267
	tcccaaaa-3′-TAMRA
Reverse	5′-cccaaaccatactgggaatact-	22	814	268
	3′

[0830]

TABLE NB
CNS_neurodegeneration_v1.0
                               Rel. Exp. (%)
                               Ag4963, Run
Tissue Name                    224735225
AD 1 Hippo                     2.4
AD 2 Hippo                     27.0
AD 3 Hippo                     7.9
AD 4 Hippo                     7.4
AD 5 Hippo                     100.0
AD 6 Hippo                     50.3
Control 2 Hippo                3.8
Control 4 Hippo                5.8
Control (Path) 3 Hippo         5.0
AD 1 Temporal Ctx              8.2
AD 2 Temporal Ctx              36.1
AD 3 Temporal Ctx              0.0
AD 4 Temporal Ctx              55.9
AD 5 Inf Temporal Ctx          90.1
AD 5 Sup Temporal Ctx          37.9
AD 6 Inf Temporal Ctx          62.0
AD 6 Sup Temporal Ctx          55.5
Control 1 Temporal Ctx         5.5
Control 2 Temporal Ctx         15.8
Control 3 Temporal Ctx         17.1
Control 3 Temporal Ctx         3.9
Control (Path) 1 Temporal Ctx  58.2
Control (Path) 2 Temporal Ctx  55.1
Control (Path) 3 Temporal Ctx  3.7
Control (Path) 4 Temporal Ctx  11.5
AD 1 Occipital Ctx             3.1
AD 2 Occipital Ctx (Missing)   0.0
AD 3 Occipital Ctx             0.0
AD 4 Occipital Ctx             40.3
AD 5 Occipital Ctx             2.1
AD 6 Occipital Ctx             8.4
Control 1 Occipital Ctx        0.0
Control 2 Occipital Ctx        20.0
Control 3 Occipital Ctx        27.2
Control 4 Occipital Ctx        4.0
Control (Path) 1 Occipital Ctx 46.3
Control (Path) 2 Occipital Ctx 7.4
Control (Path) 3 Occipital Ctx 0.0
Control (Path) 4 Occipital Ctx 3.7
Control 1 Parietal Ctx         6.3
Control 2 Parietal Ctx         24.5
Control 3 Parietal Ctx         19.5
Control (Path) 1 Parietal Ctx  44.4
Control (Path) 2 Parietal Ctx  37.6
Control (Path) 3 Parietal Ctx  4.2
Control (Path) 4 Parietal Ctx  30.6

[0831]

TABLE NC
General_screening_panel_v1.5
	Rel. Exp. (%)	Rel. Exp. (%)
	Ag4963, Run	Ag4963, Run
Tissue Name	228903693	244628523
Adipose	46.7	40.6
Melanoma* Hs688(A).T	2.1	1.8
Melanoma* Hs688(B).T	3.3	2.2
Melanoma* M14	0.0	0.0
Melanoma* LOXIMVI	0.0	0.0
Melanoma* SK-MEL-5	0.8	0.0
Squamous cell carcinoma SCC-4	5.6	1.9
Testis Pool	15.0	13.0
Prostate ca.* (bone met) PC-3	2.2	2.3
Prostate Pool	2.3	5.1
Placenta	1.6	0.7
Uterus Pool	3.4	4.0
Ovarian ca. OVCAR-3	5.2	5.3
Ovarian ca. SK-OV-3	3.3	3.3
Ovarian ca. OVCAR-4	3.5	1.6
Ovarian ca. OVCAR-5	3.4	3.2
Ovarian ca. IGROV-1	10.3	4.6
Ovarian ca. OVCAR-8	0.7	0.4
Ovary	9.7	3.3
Breast ca. MCF-7	19.1	11.1
Breast ca. MDA-MB-231	4.7	2.3
Breast ca. BT 549	13.0	7.9
Breast ca. T47D	1.4	0.0
Breast ca. MDA-N	0.0	0.0
Breast Pool	12.7	10.6
Trachea	6.4	4.7
Lung	3.0	1.1
Fetal Lung	46.7	48.0
Lung ca. NCI-N417	0.0	0.8
Lung ca. LX-1	1.0	0.1
Lung ca. NCI-H146	0.0	0.0
Lung ca. SHP-77	24.8	1.1
Lung ca. A549	1.8	2.4
Lung ca. NCI-H526	0.0	0.0
Lung ca. NCI-H23	0.0	0.0
Lung ca. NCI-H460	0.0	11.5
Lung ca. HOP-62	3.3	0.5
Lung ca. NCI-H522	6.9	10.3
Liver	0.0	0.0
Fetal Liver	10.4	7.6
Liver ca. HepG2	9.5	2.3
Kidney Pool	18.0	16.7
Fetal Kidney	100.0	100.0
Renal ca. 786-0	4.5	4.2
Renal ca. A498	5.8	4.8
Renal ca. ACHN	1.0	2.7
Renal ca. UO-31	11.0	8.2
Renal ca. TK-10	6.5	5.3
Bladder	17.3	14.4
Gastric ca. (liver met.) NCI-N87	41.8	26.6
Gastric ca. KATO III	2.9	3.5
Colon ca. SW-948	2.0	0.0
Colon ca. SW480	1.9	0.9
Colon ca.* (SW480 met) SW620	0.0	0.0
Colon ca. HT29	1.6	0.2
Colon ca. HCT-116	16.3	8.4
Colon ca. CaCo-2	24.7	15.0
Colon cancer tissue	0.6	0.0
Colon ca. SW1116	0.0	0.0
Colon ca. Colo-205	0.0	0.0
Colon ca. SW-48	0.0	0.0
Colon Pool	13.5	9.0
Small Intestine Pool	7.0	2.6
Stomach Pool	12.9	7.9
Bone Marrow Pool	6.7	6.7
Fetal Heart	28.3	21.0
Heart Pool	6.5	5.9
Lymph Node Pool	15.7	12.9
Fetal Skeletal Muscle	3.5	1.4
Skeletal Muscle Pool	4.2	6.0
Spleen Pool	9.3	3.6
Thymus Pool	29.9	31.9
CNS cancer (glio/astro) U87-MG	3.1	1.9
CNS cancer (glio/astro) U-118-MG	9.3	4.3
CNS cancer (neuro; met) SK-N-AS	0.0	1.2
CNS cancer (astro) SF-539	2.0	0.8
CNS cancer (astro) SNB-75	6.0	5.3
CNS cancer (glio) SNB-19	9.9	6.7
CNS cancer (glio) SF-295	7.2	8.0
Brain (Amygdala) Pool	10.2	4.3
Brain (cerebellum)	16.5	11.6
Brain (fetal)	17.9	16.6
Brain (Hippocampus) Pool	7.6	4.6
Cerebral Cortex Pool	7.5	3.8
Brain (Substantia nigra) Pool	3.0	5.9
Brain (Thalamus) Pool	11.7	9.2
Brain (whole)	4.6	8.5
Spinal Cord Pool	7.3	4.4
Adrenal Gland	29.9	14.1
Pituitary gland Pool	12.7	6.3
Salivary Gland	0.7	0.6
Thyroid (female)	5.4	4.0
Pancreatic ca. CAPAN2	20.2	23.0
Pancreas Pool	24.0	16.6

[0832]

TABLE ND
Panel 4.1D
                                 Rel. Exp. (%)
                                 Ag4963, Run
Tissue Name                      223691584
Secondary Th1 act                5.4
Secondary Th2 act                9.6
Secondary Tr1 act                5.1
Secondary Th1 rest               0.0
Secondary Th2 rest               0.0
Secondary Tr1 rest               12.4
Primary Th1 act                  13.0
Primary Th2 act                  0.0
Primary Tr1 act                  8.0
Primary Th1 rest                 0.0
Primary Th2 rest                 0.0
Primary Tr1 rest                 5.2
CD45RA CD4 lymphocyte act        15.1
CD45RO CD4 lymphocyte act        10.9
CD8 lymphocyte act               7.0
Secondary CD8 lymphocyte rest    11.2
Secondary CD8 lymphocyte act     0.0
CD4 lymphocyte none              1.7
2ry Th1/Th2/Tr1_anti-CD95 CH11   12.5
LAK cells rest                   4.5
LAK cells IL-2                   12.1
LAK cells IL-2 + IL-12           4.5
LAK cells IL-2 + IFN gamma       0.0
LAK cells IL-2 + IL-18           19.9
LAK cells PMA/ionomycin          0.0
NK Cells IL-2 rest               15.8
Two Way MLR 3 day                7.1
Two Way MLR 5 day                0.0
Two Way MLR 7 day                0.0
PBMC rest                        5.2
PBMC PWM                         8.2
PBMC PHA-L                       15.2
Ramos (B cell) none              7.6
Ramos (B cell) ionomycin         0.0
B lymphocytes PWM                12.9
B lymphocytes CD40L and IL-4     32.8
EOL-1 dbcAMP                     10.2
EOL-1 dbcAMP PMA/ionomycin       0.0
Dendritic cells none             0.0
Dendritic cells LPS              0.0
Dendritic cells anti-CD40        0.0
Monocytes rest                   5.2
Monocytes LPS                    0.0
Macrophages rest                 4.0
Macrophages LPS                  0.0
HUVEC none                       3.6
HUVEC starved                    0.0
HUVEC IL-1beta                   6.9
HUVEC IFN gamma                  62.4
HUVEC TNF alpha + IFN gamma      0.0
HUVEC TNF alpha + IL4            0.0
HUVEC IL-11                      16.4
Lung Microvascular EC none       0.0
Lung Microvascular EC TNFalpha + 12.5
IL-1beta
Microvascular Dermal EC none     25.5
Microsvasular Dermal EC          41.2
TNFalpha + IL-1beta
Bronchial epithelium TNFalpha +  26.2
IL1beta
Small airway epithelium none     0.0
Small airway epithelium          90.8
TNFalpha + IL-1beta
Coronery artery SMC rest         10.6
Coronery artery SMC TNFalpha +   5.3
IL-1beta
Astrocytes rest                  44.1
Astrocytes TNFalpha + IL-1beta   33.7
KU-812 (Basophil) rest           7.5
KU-812 (Basophil) PMA/ionomycin  40.1
CCD1106 (Keratinocytes) none     36.1
CCD1106 (Keratinocytes)          21.5
TNFalpha + IL-1beta
Liver cirrhosis                  8.8
NCI-H292 none                    15.3
NCI-H292 IL-4                    23.5
NCI-H292 IL-9                    14.2
NCI-H292 IL-13                   31.4
NCI-H292 IFN gamma               5.3
HPAEC none                       22.8
HPAEC TNF alpha + IL-1 beta      5.8
Lung fibroblast none             18.4
Lung fibroblast TNF alpha + IL-1 0.0
beta
Lung fibroblast IL-4             14.0
Lung fibroblast IL-9             4.9
Lung fibroblast IL-13            6.3
Lung fibroblast IFN gamma        4.3
Dermal fibroblast CCD1070 rest   4.8
Dermal fibroblast CCD1070 TNF    5.3
alpha
Dermal fibroblast CCD1070 IL-1   5.1
beta
Dermal fibroblast IFN gamma      4.5
Dermal fibroblast IL-4           5.0
Dermal Fibroblasts rest          14.5
Neutrophils TNFa + LPS           0.0
Neutrophils rest                 4.2
Colon                            16.2
Lung                             61.1
Thymus                           100.0
Kidney                           43.5

[0833]

TABLE NE
Panel 5 Islet
	Rel. Exp. (%)	Rel. Exp. (%)
	Ag4963, Run	Ag4963, Run
Tissue Name	233698024	245232951
97457_Patient-02go_adipose	81.8	74.7
97476_Patient-07sk—	39.5	52.1
skeletal muscle
97477_Patient-07ut_uterus	0.0	98.6
97478_Patient-07pl_placenta	0.0	27.4
99167_Bayer Patient 1	42.3	45.7
97482_Patient-08ut_uterus	16.2	20.6
97483_Patient-08pl_placenta	9.8	40.9
97486_Patient-09sk—	0.0	0.0
skeletal muscle
97487_Patient-09ut_uterus	14.6	28.1
97488_Patient-09pl_placenta	0.0	0.0
97492_Patient-10ut_uterus	0.0	36.6
97493_Patient-10pl_placenta	15.2	60.3
97495_Patient-11go_adipose	10.2	23.8
97496_Patient-11sk—	0.0	8.2
skeletal muscle
97497_Patient-11ut_uterus	10.7	23.7
97498_Patient-11pl_placenta	5.5	12.8
97500_Patient-12go_adipose	31.9	100.0
97501_Patient-12sk—	54.3	75.8
skeletal muscle
97502_Patient-12ut_uterus	18.0	55.1
97503_Patient-12pl_placenta	0.0	38.7
94721_Donor 2 U -	0.0	27.9
A_Mesenchymal Stem Cells
94722_Donor 2 U -	0.0	0.0
B_Mesenchymal Stem Cells
94723_Donor 2 U -	0.0	0.0
C_Mesenchymal Stem Cells
94709_Donor 2 AM - A_adipose	13.2	0.0
94710_Donor 2 AM - B_adipose	13.7	0.0
94711_Donor 2 AM - C_adipose	4.5	0.0
94712_Donor 2 AD - A_adipose	16.0	0.0
94713_Donor 2 AD - B_adipose	15.7	0.0
94714_Donor 2 AD - C_adipose	12.4	0.0
94742_Donor 3 U -	11.0	0.0
A_Mesenchymal Stem Cells
94743_Donor 3 U -	16.6	0.0
B_Mesenchymal Stem Cells
94730_Donor 3 AM - A_adipose	14.0	31.6
94731_Donor 3 AM - B_adipose	0.0	0.0
94732_Donor 3 AM - C_adipose	11.0	14.5
94733_Donor 3 AD - A_adipose	16.7	42.6
94734_Donor 3 AD - B_adipose	0.0	0.0
94735_Donor 3 AD - C_adipose	9.7	19.3
77138_Liver_HepG2untreated	61.1	72.2
73556_Heart_Cardiac stromal	11.0	0.0
cells (primary)
81735_Small Intestine	77.9	76.8
72409_Kidney_Proximal	8.2	0.0
Convoluted Tubule
82685_Small intestine_Duodenum	0.0	0.0
90650_Adrenal_Adrenocortical	0.0	0.0
adenoma
72410_Kidney_HRCE	100.0	0.0
72411_Kidney_HRE	0.0	31.6
73139_Uterus_Uterine smooth	0.0	0.0
muscle cells

[0834] CNS_neurodegeneration_v1.0 Summary: Ag4963 This panel confirms the expression of this gene at low levels in the brain in an independent group of individuals. This gene appears to be slightly upregulated in the temporal cortex of Alzheimer's disease patients. Therefore, therapeutic modulation of the expression or function of this gene may decrease neuronal death and be of use in the treatment of this disease.

[0835] General_screening_panel_v—1.5 Summary: Ag4963 Two experiments with the same probe and primer set produce results that are in excellent agreement, with highest expression in fetal kidney (CT=30). This gene is homologous to the SA protein that is also expressed in human kidney and may play a role in blood pressure regulation in rodent models of genetic hypertension (Samani NJ. Biochem Biophys Res Commun March 15, 1994; 199(2):862-8). In addition, this gene appears to be overexpressed in fetal lung (CTs=30) when compared to expression in the adult counterpart (CT=35). Thus, expression of this gene could be used to differentiate between the fetal and adult source of this tissue. In addition, modulation of the expression or function of this gene may be useful in the treatment of diseases of this organ.

[0836] Among tissues with metabolic function, this gene is expressed at moderate to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, fetal liver, skeletal muscle and fetal and adult and fetal skeletal 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.

[0837] 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 neurological disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.

[0838] Panel 4.1D Summary: Ag4963 Highest expression of this gene is seen in the thymus (CT=32.4). Low but significant expression is also seen in IFN-gamma treated KUVECs, IL-13 and IL-14 treated NCI—H292 cells, untreated IHPAECs and lung fibroblasts, normal lung and kidney. Thus, this gene product may play an important role in T cell development. Therapeutic modulation of the expression or function of this gene may be utilized to modulate immune function (T cell development) and be important for organ transplant, AIDS treatment or post chemotherapy immune reconstitution.

[0839] Panel 5 Islet Summary: Ag4963 Two experiments with the same probe and primer show this gene expressed at low levels in adipose and a kidney cell line (CTs=34.5).

[0840] O. CG138563-01: CHOLINE/ETHANOLAMINE KINASE-Like Gene

[0841] Expression of gene CG138563-01 was assessed using the primer-probe sets Ag4972 and Ag5937, described in Tables OA and OB. Results of the RTQ-PCR runs are shown in Tables OC, OD and OE.

TABLE OA
Probe Name Ag4972
			Start	SEQ
Primers	Sequences	Length	Position	ID No
Forward	5′-	22	777	269
	ggagcggtacctaaaacagatc-
	3′
Probe	TET-5′-	25	813	270
	aactggcctccctgagatgaacctg-
	3′-TAMRA
Reverse	5′-	22	844	271
	tctcatccttcaggctgtacat-
	3′

[0842]

TABLE OB
Probe Name Ag5937
			Start	SEQ
Primers	Sequences	Length	Position	ID No
Forward	5′-	22	842	272
	agatgtacagcctgaaggatga-
	3′
Probe	TET-5′-	25	926	273
	acatccaggaaggtaggagaaggca-
	3′-TAMRA
Reverse	5′-tgaggttctgctcactccaga-	21	989	274
	3′

[0843]

TABLE OC
General_screening_panel_v1.5
	Rel. Exp. (%)	Rel. Exp. (%)
	Ag4972, Run	Ag5937, Run
Tissue Name	228926672	247834840
Adipose	13.7	11.3
Melanoma* Hs688(A).T	19.5	17.8
Melanoma* Hs688(B).T	18.2	18.2
Melanoma* M14	44.4	57.4
Melanoma* LOXIMVI	15.6	16.6
Melanoma* SK-MEL-5	35.6	25.2
Squamous cell carcinoma SCC-4	9.2	16.4
Testis Pool	20.6	17.8
Prostate ca.* (bone met) PC-3	36.1	49.0
Prostate Pool	21.8	26.6
Placenta	23.0	15.1
Uterus Pool	13.6	10.4
Ovarian ca. OVCAR-3	15.3	14.2
Ovarian ca. SK-OV-3	59.5	55.5
Ovarian ca. OVCAR-4	13.4	7.4
Ovarian ca. OVCAR-5	41.8	64.2
Ovarian ca. IGROV-1	17.6	10.4
Ovarian ca. OVCAR-8	14.4	9.7
Ovary	10.6	11.7
Breast ca. MCF-7	22.1	48.0
Breast ca. MDA-MB-231	28.3	32.3
Breast ca. BT 549	35.1	63.7
Breast ca. T47D	5.3	6.2
Breast ca. MDA-N	11.4	12.3
Breast Pool	24.1	25.2
Trachea	22.8	29.9
Lung	9.0	13.2
Fetal Lung	37.9	37.4
Lung ca. NCI-N417	3.0	3.3
Lung ca. LX-1	25.5	31.0
Lung ca. NCI-H146	6.3	7.4
Lung ca. SHP-77	25.9	50.0
Lung ca. A549	16.4	18.7
Lung ca. NCI-H526	4.3	3.6
Lung ca. NCI-H23	40.1	54.7
Lung ca. NCI-H460	23.3	28.9
Lung ca. HOP-62	25.7	16.0
Lung ca. NCI-H522	47.0	82.4
Liver	2.5	1.9
Fetal Liver	19.9	20.0
Liver ca. HepG2	17.7	23.7
Kidney Pool	32.3	47.6
Fetal Kidney	27.4	37.9
Renal ca. 786-0	32.8	50.0
Renal ca. A498	6.3	6.3
Renal ca. ACHN	19.6	18.0
Renal ca. UO-31	27.2	39.5
Renal ca. TK-10	26.8	31.0
Bladder	54.7	86.5
Gastric ca. (liver met.)	100.0	78.5
NCI-N87
Gastric ca. KATO III	44.8	59.5
Colon ca. SW-948	12.6	9.8
Colon ca. SW480	28.1	32.8
Colon ca.* (SW480 met)	17.4	23.3
SW620
Colon ca. HT29	6.1	8.6
Colon ca. HCT-116	28.5	44.4
Colon ca. CaCo-2	34.2	63.3
Colon cancer tissue	22.1	27.2
Colon ca. SW1116	8.4	7.0
Colon ca. Colo-205	6.9	5.7
Colon ca. SW-48	7.5	5.3
Colon Pool	10.4	27.0
Small Intestine Pool	21.0	27.0
Stomach Pool	13.8	15.5
Bone Marrow Pool	8.8	9.7
Fetal Heart	23.2	23.2
Heart Pool	11.0	11.0
Lymph Node Pool	22.1	38.7
Fetal Skeletal Muscle	9.2	5.5
Skeletal Muscle Pool	22.7	27.7
Spleen Pool	39.5	48.3
Thymus Pool	40.9	61.6
CNS cancer (glio/astro)	46.7	36.9
U87-MG
CNS cancer (glio/astro)	48.0	90.8
U-118-MG
CNS cancer (neuro; met)	23.0	15.3
SK-N-AS
CNS cancer (astro) SF-539	14.6	25.5
CNS cancer (astro) SNB-75	33.0	46.0
CNS cancer (glio) SNB-19	16.0	12.8
CNS cancer (glio) SF-295	56.6	90.8
Brain (Amygdala) Pool	12.7	13.5
Brain (cerebellum)	82.9	100.0
Brain (fetal)	39.5	51.1
Brain (Hippocampus) Pool	11.2	12.9
Cerebral Cortex Pool	9.5	17.1
Brain (Substantia nigra)	12.4	19.1
Pool
Brain (Thalamus) Pool	15.3	16.4
Brain (whole)	11.3	19.2
Spinal Cord Pool	14.3	12.3
Adrenal Gland	28.3	31.6
Pituitary gland Pool	10.5	11.2
Salivary Gland	14.6	15.1
Thyroid (female)	11.4	9.0
Pancreatic ca. CAPAN2	26.2	37.4
Pancreas Pool	34.6	31.9

[0844]

TABLE OD
Oncology_cell_line_screening_panel_v3.1
                                 Rel. Exp. (%)
                                 Ag4972, Run
Tissue Name                      225061002
Daoy                             9.0
Medulloblastoma/Cerebellum
TE671                            9.6
Medulloblastom/Cerebellum
D283 Med                         31.0
Medulloblastoma/Cerebellum
PFSK-1 Primitive                 19.5
Neuroectodermal/Cerebellum
XF-498_CNS                       28.9
SNB-78_CNS/glioma                18.6
SF-268_CNS/glioblastoma          10.6
T98G_Glioblastoma                39.2
SK-N-SH_Neuroblastoma            36.9
(metastasis)
SF-295_CNS/glioblastoma          24.7
Cerebellum                       100.0
Cerebellum                       72.7
NCI-H292_Mucoepidermoid          25.5
lung ca.
DMS-114_Small cell lung          9.7
cancer
DMS-79_Small cell lung           21.2
cancer/neuroendocrine
NCI-H146_Small cell lung         19.3
cancer/neuroendocrine
NCI-H526_Small cell lung         26.6
cancer/neuroendocrine
NCI-N417_Small cell lung         11.0
cancer/neuroendocrine
NCI-H82_Small cell lung          11.0
cancer/neuroendocrine
NCI-H157_Squamous cell lung      19.9
cancer (metastasis)
NCI-H1155_Large cell lung        69.7
cancer/neuroendocrine
NCI-H1299_Large cell lung        20.7
cancer/neuroendocrine
NCI-H727_Lung carcinoid          37.6
NCI-UMC-11_Lung carcinoid        61.6
LX-1_Small cell lung cancer      15.7
Colo-205_Colon cancer            17.8
KM12_Colon cancer                39.8
KM20L2_Colon cancer              6.1
NCI-H716_Colon cancer            80.1
SW-48_Colon adenocarcinoma       24.1
SW1116_Colon adenocarcinoma      14.4
LS 174T_Colon adenocarcinoma     19.8
SW-948_Colon adenocarcinoma      31.2
SW-480_Colon adenocarcinoma      17.6
NCI-SNU-5_Gastric ca.            19.9
KATO III_Stomach                 23.5
NCI-SNU-16_Gastric ca.           14.7
NCI-SNU-1_Gastric ca.            30.8
RF-1_Gastric adenocarcinoma      22.5
RF-48_Gastric adenocarcinoma     20.3
MKN-45_Gastric ca.               24.7
NCI-N87_Gastric ca.              21.6
OVCAR-5_Ovarian ca.              9.2
RL95-2_Uterine carcinoma         22.4
HelaS3_Cervical adenocarcinoma   22.2
Ca Ski_Cervical epidermoid carcinoma 71.2
(metastasis)
ES-2_Ovarian clear cell carcinoma 10.3
Ramos/6 h stim_Stimulated with   37.9
PMA/ionomycin 6 h
Ramos/14 h stim_Stimulated with  16.0
PMA/ionomycin 14 h
MEG-01_Chronic myelogenous       18.0
leukemia (megokaryoblast)
Raji_Burkitt's lymphoma          19.2
Daudi_Burkitt's lymphoma         40.1
U266_B-cell plasmacytoma/myeloma 10.1
CA46_Burkitt's lymphoma          9.3
RL_non-Hodgkin's B-cell lymphoma 6.5
JM1_pre-B-cell lymphoma/leukemia 12.7
Jurkat_T cell leukemia           23.2
TF-1_Erythroleukemia             31.4
HUT 78_T-cell lymphoma           56.6
U937_Histiocytic lymphoma        17.4
KU-812_Myelogenous leukemia      28.3
769-P_Clear cell renal ca.       12.2
Caki-2_Clear cell renal ca.      35.4
SW 839_Clear cell renal ca.      32.1
G401_Wilms' tumor                14.8
Hs766T_Pancreatic ca. (LN metastasis) 29.7
CAPAN-1_Pancreatic adenocarcinoma 21.3
(liver metastasis)
SU86.86_Pancreatic carcinoma (liver 39.5
metastasis)
BxPC-3_Pancreatic adenocarcinoma 26.2
HPAC_Pancreatic adenocarcinoma   83.5
MIA PaCa-2_Pancreatic ca.        5.3
CFPAC-1_Pancreatic ductal        84.1
adenocarcinoma
PANC-1_Pancreatic epithelioid ductal 27.2
ca.
T24_Bladder ca. (transitional cell) 30.1
5637_Bladder ca.                 14.4
HT-1197_Bladder ca.              61.6
UM-UC-3_Bladder ca. (transitional 7.4
cell)
A204_Rhabdomyosarcoma            12.6
HT-1080_Fibrosarcoma             24.3
MG-63_Osteosarcoma (bone)        10.1
SK-LMS-1_Leiomyosarcoma (vulva)  27.5
SJRH30_Rhabdomyosarcoma (met to  22.7
bone marrow)
A431_Epidermoid ca.              59.5
WM266-4_Melanoma                 20.4
DU 145_Prostate                  30.1
MDA-MB-468_Breast adenocarcinoma 17.9
SSC-4_Tongue                     12.2
SSC-9_Tongue                     12.4
SSC-15_Tongue                    19.8
CAL 27_Squamous cell ca. of tongue 33.4

[0845]

TABLE OE
Panel 5 Islet
	Rel. Exp. (%)	Rel. Exp. (%)
	Ag4972, Run	Ag5937, Run
Tissue Name	240188657	247837926
97457_Patient-02go_adipose	44.4	56.3
97476_Patient-07sk—	13.2	30.6
skeletal muscle
97477_Patient-07ut_uterus	11.0	12.2
97478_Patient-07pl_placenta	22.5	20.7
99167_Bayer Patient 1	57.8	37.1
97482_Patient-08ut_uterus	10.1	9.7
97483_Patient-08pl_placenta	21.3	12.2
97486_Patient-09sk—	2.6	3.2
skeletal muscle
97487_Patient-09ut_uterus	13.5	27.2
97488_Patient-09pl_placenta	14.2	19.3
97492_Patient-10ut_uterus	16.2	38.7
97493_Patient-10pl_placenta	53.2	42.6
97495_Patient-11go_adipose	20.9	28.5
97496_Patient-11sk—	14.7	14.0
skeletal muscle
97497_Patient-11ut_uterus	18.2	36.9
97498_Patient-11pl_placenta	10.8	23.2
97500_Patient-12go_adipose	49.3	40.3
97501_Patient-12sk—	46.7	38.7
skeletal muscle
97502_Patient-12ut_uterus	21.3	23.7
97503_Patient-12pl_placenta	20.6	18.6
94721_Donor 2 U -	18.0	18.8
A_Mesenchymal Stem Cells
94722_Donor 2 U -	11.7	10.4
B_Mesenchymal Stem Cells
94723_Donor 2 U -	23.8	15.8
C_Mesenchymal Stem Cells
94709_Donor 2 AM - A_adipose	25.5	15.5
94710_Donor 2 AM - B_adipose	11.7	8.5
94711_Donor 2 AM - C_adipose	10.8	5.0
94712_Donor 2 AD - A_adipose	22.5	20.7
94713_Donor 2 AD - B_adipose	17.0	15.2
94714_Donor 2 AD - C_adipose	17.8	18.9
94742_Donor 3 U -	9.6	5.0
A_Mesenchymal Stem Cells
94743_Donor 3 U -	12.5	21.3
B_Mesenchymal Stem Cells
94730_Donor 3 AM - A_adipose	14.1	25.0
94731_Donor 3 AM - B_adipose	9.9	10.4
94732_Donor 3 AM - C_adipose	17.0	8.7
94733_Donor 3 AD - A_adipose	27.5	16.6
94734_Donor 3 AD - B_adipose	4.7	3.0
94735_Donor 3 AD - C_adipose	17.1	11.2
77138_Liver_HepG2untreated	26.2	39.2
73556_Heart_Cardiac stromal	24.3	43.2
cells (primary)
81735_Small Intestine	41.8	59.0
72409_Kidney_Proximal	15.6	25.9
Convoluted Tubule
82685_Small intestine_Duodenum	5.4	21.9
90650_Adrenal_Adrenocortical	12.8	7.0
adenoma
72410_Kidney_HRCE	100.0	100.0
72411_Kidney_HRE	40.3	66.4
73139_Uterus_Uterine smooth	13.5	22.7
muscle cells

[0846] General_screening_panel_v1.5 Summary: Ag4972/Ag5937 Two experiments with two different probe and primer sets produce results that are in very good agreement. Highest expression of this gene is seen in a gastric cancer cell line (CT=26) and the cerebellum (CT=29). This gene encodes a homolog of ethanolaamine kinase that catalyzes the first step of PtdEtn biosynthesis, an abundant phospholipid in eukaryotic cell membranes. This gene is widely expressed in this panel, with moderate 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.

[0847] 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.

[0848] In addition, this gene is expressed at much higher levels in fetal liver tissue (CTs=29-3 1) 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 source of this tissue. In addition, therapeutic modulation of this gene may be useful in the treatment of diseases of this tissue.

[0849] 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.

[0850] Oncology_cell_line_screening_panel_—3.1 Summary: Ag4972 Highest expression of this gene is seen in the cerebellum (CT=29), consistent with expression in Panel 1.5. In addition, this gene is widely expressed in the cancer cell line samples on this panel.

[0851] Panel 5 Islet Summary: Ag4972/Ag5937 Two experiments with two different probe and primer sets produce results that are in very good agreement. Highest expression of this gene is seen in kidney (CTs=29-32). This gene is widely expressed on this panel, consistent with expression in the other panels. Moderate levels of expression are seen in metabolic tissues, including adipose, placenta and skeletal muscle. Please see Panel 1.5 for discussion of utility of this gene in metabolic disease.

[0852] P. CG140041-01: Pyridoxal-Dependent Decarboxylase-Like Gene

[0853] Expression of gene CG140041-01 was assessed using the primer-probe set Ag4979, described in Table PA.

TABLE PA
Probe Name Ag4979
			Start	SEQ
Primers	Sequences	Length	Position	ID No
Forward	5′-	21	1732	275
	tgctggactcctgaagaagtt-
	3′
Probe	TET-5′-	27	1768	276
	tgacctaacctttaaaataggccctga-
	3′-TAMRA
Reverse	5′-gacataaaggcagctcttcatg-	22	1804	277
	3′

[0854] Q. CG140061-01: IMP Dehydrogenase-Like Gene

[0855] Expression of gene CG140061-01 was assessed using the primer-probe set Ag4980, described in Table QA. Results of the RTQ-PCR runs are shown in Tables QB and QC.

TABLE QA
Probe Name Ag4980
			Start	SEQ
Primers	Sequences	Length	Position	ID No
Forward	5′-	22	1533	278
	gtactcaggggagctcaagttt-
	3′
Probe	TET-5′-	23	1562	279
	agaccatgtcggcccagatcaag-
	3′-TAMRA
Reverse	5′-	22	1609	280
	ctcatcacagctgcttctcata-
	3′

[0856]

TABLE QB
General screening_panel v1.4
                                 Rel. Exp. (%)
                                 Ag4980, Run
Tissue Name                      218306194
Adipose                          0.0
Melanoma* Hs688(A).T             9.8
Melanoma* Hs688(B).T             9.0
Melanoma* M14                    2.1
Melanoma* LOXIMVI                4.8
Melanoma* SK-MEL-5               2.7
Squamous cell carcinoma          6.5
SCC-4
Testis Pool                      100.0
Prostate ca.* (bone met) PC-3    79.6
Prostate Pool                    2.5
Placenta                         18.2
Uterus Pool                      0.0
Ovarian ca. OVCAR-3              14.1
Ovarian ca. SK-OV-3              27.5
Ovarian ca. OVCAR-4              5.8
Ovarian ca. OVCAR-5              76.3
Ovarian ca. IGROV-1              9.9
Ovarian ca. OVCAR-8              4.3
Ovary                            8.0
Breast ca. MCF-7                 63.3
Breast ca. MDA-MB-231            14.5
Breast ca. BT 549                23.2
Breast ca. T47D                  87.7
Breast ca. MDA-N                 1.9
Breast Pool                      7.2
Trachea                          6.2
Lung                             0.0
Fetal Lung                       8.3
Lung ca. NCI-N417                1.7
Lung ca. LX-1                    29.9
Lung ca. NCI-H146                1.2
Lung ca. SHP-77                  3.0
Lung ca. A549                    17.1
Lung ca. NCI-H526                1.1
Lung ca. NCI-H23                 11.6
Lung ca. NCI-H460                6.2
Lung ca. HOP-62                  3.4
Lung ca. NCI-H522                17.9
Liver                            0.0
Fetal Liver                      1.6
Liver ca. HepG2                  8.3
Kidney Pool                      23.8
Fetal Kidney                     3.4
Renal ca. 786-0                  12.6
Renal ca. A498                   11.7
Renal ca. ACHN                   4.4
Renal ca. UO-31                  6.0
Renal ca. TK-10                  15.1
Bladder                          8.0
Gastric ca. (liver met.) NCI-N87 45.7
Gastric ca. KATO III             14.4
Colon ca. SW-948                 3.6
Colon ca. SW480                  9.4
Colon ca.* (SW480 met) SW620     9.3
Colon ca. HT29                   5.4
Colon ca. HCT-116                19.5
Colon ca. CaCo-2                 22.7
Colon cancer tissue              2.1
Colon ca. SW1116                 2.6
Colon ca. Colo-205               1.4
Colon ca. SW-48                  3.1
Colon Pool                       7.1
Small Intestine Pool             5.6
Stomach Pool                     4.9
Bone Marrow Pool                 0.0
Fetal Heart                      0.0
Heart Pool                       4.3
Lymph Node Pool                  10.7
Fetal Skeletal Muscle            1.3
Skeletal Muscle Pool             3.3
Spleen Pool                      4.6
Thymus Pool                      6.2
CNS cancer (glio/astro) U87-MG   7.2
CNS cancer (glio/astro)          11.2
U-118-MG
CNS cancer (neuro; met)          19.8
SK-N-AS
CNS cancer (astro) SF-539        3.6
CNS cancer (astro) SNB-75        15.9
CNS cancer (glio) SNB-19         8.3
CNS cancer (glio) SF-295         7.3
Brain (Amygdala) Pool            0.0
Brain (cerebellum)               0.0
Brain (fetal)                    6.2
Brain (Hippocampus) Pool         0.0
Cerebral Cortex Pool             1.1
Brain (Substantia nigra) Pool    0.0
Brain (Thalamus) Pool            1.7
Brain (whole)                    2.6
Spinal Cord Pool                 0.0
Adrenal Gland                    28.1
Pituitary gland Pool             0.0
Salivary Gland                   4.7
Thyroid (female)                 4.0
Pancreatic ca. CAPAN2            33.9
Pancreas Pool                    13.6

[0857]

TABLE QC
Panel 4.1D
                                 Rel. Exp. (%)
                                 Ag4980, Run
Tissue Name                      223693388
Secondary Th1 act                0.0
Secondary Th2 act                3.0
Secondary Tr1 act                5.7
Secondary Th1 rest               9.2
Secondary Th2 rest               7.6
Secondary Tr1 rest               0.0
Primary Th1 act                  0.0
Primary Th2 act                  0.0
Primary Tr1 act                  4.8
Primary Th1 rest                 0.0
Primary Th2 rest                 0.0
Primary Tr1 rest                 3.6
CD45RA CD4 lymphocyte act        3.0
CD45RO CD4 lymphocyte act        0.0
CD8 lymphocyte act               0.0
Secondary CD8 lymphocyte         3.1
rest
Secondary CD8 lymphocyte         0.0
act
CD4 lymphocyte none              0.0
2ry Thl/Th2/Trl_anti-CD95        6.3
CH11
LAK cells rest                   0.0
LAK cells IL-2                   6.7
LAK cells IL-2 + IL-12           0.0
LAK cells IL-2 + IFN gamma       0.0
LAK cells IL-2 + IL-18           0.0
LAK cells PMA/ionomycin          0.0
NK Cells IL-2 rest               17.0
Two Way MLR 3 day                4.0
Two Way MLR 5 day                0.0
Two Way MLR 7 day                0.0
PBMC rest                        0.0
PBMC PWM                         0.0
PBMC PHA-L                       3.1
Ramos (B cell) none              0.0
Ramos (B cell) ionomycin         0.0
B lymphocytes PWM                4.0
B lymphocytes CD40L and          3.8
IL-4
EOL-1 dbcAMP                     0.0
EOL-1 dbcAMP                     0.0
PMA/ionomycin
Dendritic cells none             0.0
Dendritic cells LPS              5.4
Dendritic cells anti-CD40        0.0
Monocytes rest                   0.0
Monocytes LPS                    4.2
Macrophages rest                 0.0
Macrophages LPS                  0.0
HUVEC none                       8.9
HUVEC starved                    8.6
HUVEC IL-1beta                   5.9
HUVEC IFN gamma                  8.1
HUVEC TNF alpha + IFN gamma      0.0
HUVEC TNF alpha + IL4            7.1
HUVEC IL-11                      6.9
Lung Microvascular EC none       22.8
Lung Microvascular EC TNFalpha + 13.6
IL-1beta
Microvascular Dermal EC none     9.5
Microsvasular Dermal EC TNFalpha + 5.0
IL-1beta
Bronchial epithelium TNFalpha +  37.9
IL1beta
Small airway epithelium none     7.6
Small airway epithelium TNFalpha + 17.8
IL-1beta
Coronery artery SMC rest         0.0
Coronery artery SMC TNFalpha +   9.6
IL-1beta
Astrocytes rest                  4.2
Astrocytes TNFalpha + IL-lbeta   10.0
KU-812 (Basophil) rest           0.0
KU-812 (Basophil) PMA/ionomycin  0.0
CCD1106 (Keratinocytes) none     21.9
CCD1106 (Keratinocytes) TNFalpha + 33.9
IL-1beta
Liver cirrhosis                  0.0
NCI-H292 none                    78.5
NCI-H292 IL-4                    100.0
NCI-H292 IL-9                    81.2
NCI-H292 IL-13                   80.7
NCI-H292 IFN gamma               44.1
HPAEC none                       10.2
HPAEC TNF alpha + IL-1 beta      25.5
Lung fibroblast none             18.9
Lung fibroblast TNF alpha + IL-1 7.0
beta
Lung fibroblast IL-4             5.3
Lung fibroblast IL-9             19.1
Lung fibroblast IL-13            7.1
Lung fibroblast IFN gamma        8.6
Dermal fibroblast CCD1070 rest   26.8
Dermal fibroblast CCD1070 TNF    21.2
alpha
Dermal fibroblast CCD1070 IL-1   13.2
beta
Dermal fibroblast IFN gamma      9.9
Dermal fibroblast IL-4           23.5
Dermal Fibroblasts rest          7.3
Neutrophils TNFa + LPS           0.0
Neutrophils rest                 0.0
Colon                            0.0
Lung                             0.0
Thymus                           8.2
Kidney                           25.5

[0858] General_screening_panel_v1.4 Summary: Ag4980 Highest expression of this gene is seen in testis (CT=33). Low but significant levels of expression are seen in cell lines derived from pancreatic, breast, ovarian, lung, and gastric cancer cell lines. This gene encodes a homologue of inosine-5-prime-monophosphate dehydrogenase (IMPD-1) that is the rate-limiting enzyme in the de novo synthesis of guanine nucleotides. Inhibition of this enzyme has been shown to exhibit anticancer activities against tumor cell lines (Jager W. Curr Med Chem April 2002;9(7):781-6). Thus, therapeutic modulation of the expression or function of this gene may be effective in the treatment of these cancers.

[0859] Panel 4.1D Summary: Ag4980 Expression of this transcript is expressed exclusively in NC—-H292 cells stimulated by IL-4 (CT=34.9). This cell line is derived from 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 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.

[0860] R. CG140335-01: UREA TRANSPORTER ISOFORM UTA-3-Like Gene

[0861] Expression of gene CG140335-01 was assessed using the primer-probe set Ag5021, described in Table RA. Results of the RTQ-PCR runs are shown in Tables RB and RC.

TABLE RA
Probe Name Ag5021
				SEQ
			Start	ID
Primers	Sequences	Length	Position	No
Forward	5′-ctttctagtgccttgaattcca-3′	22	660	281
Probe	TET-5′-	26	690	282
	aagtgggacctcccggtcttcactct-
	3′-TAMRA
Reverse	5′-ggtacaaggtgactgcaatgtt-3′	22	723	283

[0862]

TABLE RB
General_screening_panel_v1.5
                                 Rel. Exp. (%)
                                 Ag5021, Run
Tissue Name                      228941110
Adipose                          38.4
Melanoma* Hs688(A).T             22.1
Melanoma* Hs688(B).T             3.7
Melanoma* M14                    0.4
Melanoma* LOXIMVI                1.6
Melanoma* SK-MEL-5               1.9
Squamous cell carcinoma          1.1
SCC-4
Testis Pool                      30.1
Prostate ca.* (bone met) PC-3    1.4
Prostate Pool                    12.7
Placenta                         0.9
Uterus Pool                      2.6
Ovarian ca. OVCAR-3              4.0
Ovarian ca. SK-OV-3              13.6
Ovarian ca. OVCAR-4              1.7
Ovarian ca. OVCAR-5              1.0
Ovarian ca. IGROV-1              11.7
Ovarian ca. OVCAR-8              1.7
Ovary                            1.2
Breast ca. MCF-7                 1.5
Breast ca. MDA-MB-231            3.4
Breast ca. BT 549                3.9
Breast ca. T47D                  0.0
Breast ca. MDA-N                 0.5
Breast Pool                      4.3
Trachea                          5.7
Lung                             0.9
Fetal Lung                       5.9
Lung ca. NCI-N417                0.0
Lung ca. LX-1                    0.0
Lung ca. NCI-H146                0.5
Lung ca. SHP-77                  0.0
Lung ca. A549                    0.5
Lung ca. NCI-H526                0.0
Lung ca. NCI-H23                 0.5
Lung ca. NCI-H460                0.9
Lung ca. HOP-62                  0.0
Lung ca. NCI-H522                0.7
Liver                            0.8
Fetal Liver                      2.0
Liver ca. HepG2                  0.0
Kidney Pool                      4.9
Fetal Kidney                     100.0
Renal ca. 786-0                  0.0
Renal ca. A498                   0.2
Renal ca. ACHN                   0.0
Renal ca. UO-31                  0.4
Renal ca. TK-10                  1.9
Bladder                          13.2
Gastric ca. (liver met.) NCI-N87 1.1
Gastric ca. KATO III             0.0
Colon ca. SW-948                 0.9
Colon ca. SW480                  0.0
Colon ca.* (SW480 met) SW620     0.0
Colon ca. HT29                   0.0
Colon ca. HCT-116                2.4
Colon ca. CaCo-2                 29.9
Colon cancer tissue              1.7
Colon ca. SW1116                 0.4
Colon ca. Colo-205               0.0
Colon ca. SW-48                  0.0
Colon Pool                       6.1
Small Intestine Pool             1.8
Stomach Pool                     1.9
Bone Marrow Pool                 0.9
Fetal Heart                      0.0
Heart Pool                       1.4
Lymph Node Pool                  1.9
Fetal Skeletal Muscle            0.5
Skeletal Muscle Pool             2.9
Spleen Pool                      5.4
Thymus Pool                      22.8
CNS cancer (glio/astro) U87-MG   7.7
CNS cancer (glio/astro)          13.7
U-118-MG
CNS cancer (neuro; met)          1.5
SK-N-AS
CNS cancer (astro) SF-539        0.4
CNS cancer (astro) SNB-75        2.7
CNS cancer (glio) SNB-19         20.2
CNS cancer (glio) SF-295         7.7
Brain (Amygdala) Pool            3.5
Brain (cerebellum)               3.2
Brain (fetal)                    9.6
Brain (Hippocampus) Pool         2.2
Cerebral Cortex Pool             4.6
Brain (Substantia nigra) Pool    4.5
Brain (Thalamus) Pool            6.5
Brain (whole)                    4.7
Spinal Cord Pool                 1.0
Adrenal Gland                    2.0
Pituitary gland Pool             0.6
Salivary Gland                   2.4
Thyroid (female)                 1.2
Pancreatic ca. CAPAN2            0.6
Pancreas Pool                    2.2

[0863]

TABLE RC
Panel 4.1D
                                 Rel. Exp. (%)
                                 Ag5021, Run
Tissue Name                      223740344
Secondary Th1 act                2.1
Secondary Th2 act                0.0
Secondary Tr1 act                0.0
Secondary Th1 rest               6.7
Secondary Th2 rest               0.0
Secondary Tr1 rest               2.7
Primary Th1 act                  7.9
Primary Th2 act                  0.0
Primary Tr1 act                  0.0
Primary Th1 rest                 0.0
Primary Th2 rest                 0.0
Primary Tr1 rest                 5.3
CD45RA CD4 lymphocyte act        4.7
CD45RO CD4 lymphocyte act        4.6
CD8 lymphocyte act               0.0
Secondary CD8 lymphocyte         2.4
rest
Secondary CD8 lymphocyte         1.4
act
CD4 lymphocyte none              0.0
2ry Thl/Th2/Trl_anti-CD95        0.0
CH11
LAK cells rest                   4.8
LAK cells IL-2                   0.0
LAK cells IL-2 + IL-12           0.0
LAK cells IL-2 + IFN gamma       4.7
LAK cells IL-2 + IL-18           2.6
LAK cells PMA/ionomycin          0.0
NK Cells IL-2 rest               10.6
Two Way MLR 3 day                2.5
Two Way MLR 5 day                2.1
Two Way MLR 7 day                5.4
PBMC rest                        0.0
PBMC PWM                         2.3
PBMC PHA-L                       21.0
Ramos (B cell) none              0.0
Ramos (B cell) ionomycin         0.0
B lymphocytes PWM                5.7
B lymphocytes CD40L and          2.6
IL-4
EOL-1 dbcAMP                     2.0
EOL-1 dbcAMP                     6.1
PMA/ionomycin
Dendritic cells none             0.0
Dendritic cells LPS              1.7
Dendritic cells anti-CD40        2.7
Monocytes rest                   0.0
Monocytes LPS                    0.0
Macrophages rest                 4.2
Macrophages LPS                  0.0
HUVEC none                       0.0
HUVEC starved                    0.0
HUVEC IL-1beta                   0.0
HUVEC IFN gamma                  0.0
HUVEC TNF alpha + IFN gamma      0.0
HUVEC TNF alpha + IL4            0.0
HUVEC IL-11                      0.0
Lung Microvascular EC none       2.1
Lung Microvascular EC TNFalpha + 1.4
IL-1beta
Microvascular Dermal EC none     0.0
Microsvasular Dermal EC          0.0
TNFalpha + IL-lbeta
Bronchial epithelium TNFalpha +  2.4
IL1beta
Small airway epithelium none     0.0
Small airway epithelium          0.0
TNFalpha + IL-lbeta
Coronery artery SMC rest         2.9
Coronery artery SMC TNFalpha +   7.5
IL-1beta
Astrocytes rest                  2.3
Astrocytes TNFalpha + IL-lbeta   5.1
KU-812 (Basophil) rest           0.0
KU-812 (Basophil) PMA/ionomycin  1.2
CCD1106 (Keratinocytes) none     1.9
CCD1106 (Keratinocytes)          0.0
TNFalpha + IL-lbeta
Liver cirrhosis                  6.6
NCI-H292 none                    4.6
NCI-H292 IL-4                    2.6
NCI-H292 IL-9                    2.2
NCI-H292 IL-13                   0.0
NCI-H292 IFN gamma               0.0
HPAEC none                       0.0
HPAEC TNF alpha + IL-1 beta      0.0
Lung fibroblast none             4.5
Lung fibroblast TNF alpha + IL-1 0.0
beta
Lung fibroblast IL-4             2.2
Lung fibroblast IL-9             0.0
Lung fibroblast IL-13            0.0
Lung fibroblast IFN gamma        0.0
Dermal fibroblast CCD1070 rest   0.0
Dermal fibroblast CCD1070 TNF    3.9
alpha
Dermal fibroblast CCD1070 IL-1   0.0
beta
Dermal fibroblast IFN gamma      0.0
Dermal fibroblast IL-4           0.4
Dermal Fibroblasts rest          2.7
Neutrophils TNFa + LPS           0.0
Neutrophils rest                 3.3
Colon                            66.4
Lung                             0.0
Thymus                           50.7
Kidney                           100.0

[0864] General_screening_panel_v1.5 Summary: Ag5021 highest expression of this gene, a Putative Urea Transporter, is seen in Fetal Kidney (CT=29.3). In addition, this gene appears to be overexpressed in fetal kidney when compared to expression in the adult counterpart. Thus, expression of this gene may be used to differentiate between the fetal and adult source of this tissue. Furthermore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of diseases of this organ.

[0865] Panel 4.1D Summary: Ag5021 Highest expression of this gene is seen in the kidney (CT=31), consistent with Panel 1.5 and the characterization of this protein as a novel urea transporter. Moderate levels of expression are also seen in thymus and colon. Thus, 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.

[0866] S. CG140355-01: PEPTIDYLPROLYL ISOMERASE A-Like Gene

[0867] Expression of gene CG140355-01 was assessed using the primer-probe set Ag5022, described in Table SA.

TABLE SA
Probe Name Ag5022
				SEQ
			Start	ID
Primers	Sequences	Length	Position	No
Forward	5′-accccaccaagttcttcaat-3′	20	35	284
Probe	TET-5′-catctccatccagctgtt	26	69	285
	tgcagaca-3′-TAMRA
Reverse	5′-ttttctgctgtctttggaaact-	22	95	286
	3′

[0868] T. CG140696-01 and CG140696-02: AAA ATPase Superfamily-Like Gene

[0869] Expression of gene CG140696-01 and variant CG140696-02 was assessed using the primer-probe set Ag5037, described in Table TA. Results of the RTQ-PCR runs are shown in Tables TB and TC.

TABLE TA
Probe Name Ag5037
				SEQ
			Start	ID
Primers	Sequences	Length	Position	No
Forward	5′-ttgaacaccttcgaccataatc-	22	636	287
	3′
Probe	TET-5′-ccctcagaacgactgctg	26	663	288
	aaacctct-3′-TAMRA
Reverse	5′-attctcgcatctcactgttcat-	22	705	289
	3′

[0870]

TABLE TB
General_screening_panel_v1.5
                                 Rel. Exp. (%)
                                 Ag5037, Run
Tissue Name                      228967211
Adipose                          9.4
Melanoma* Hs688(A).T             7.4
Melanoma* Hs688(B).T             7.4
Melanoma* M14                    3.3
Melanoma* LOXIMVI                1.8
Melanoma* SK-MEL-5               35.6
Squamous cell carcinoma          9.2
SCC-4
Testis Pool                      48.0
Prostate ca.* (bone met) PC-3    44.8
Prostate Pool                    8.9
Placenta                         0.5
Uterus Pool                      3.4
Ovarian ca. OVCAR-3              51.8
Ovarian ca. SK-OV-3              3.7
Ovarian ca. OVCAR-4              11.7
Ovarian ca. OVCAR-5              44.4
Ovarian ca. IGROV-1              3.8
Ovarian ca. OVCAR-8              1.4
Ovary                            7.5
Breast ca. MCF-7                 11.0
Breast ca. MDA-MB-231            1.6
Breast ca. BT 549                58.2
Breast ca. T47D                  48.6
Breast ca. MDA-N                 3.4
Breast Pool                      11.4
Trachea                          14.3
Lung                             1.8
Fetal Lung                       22.8
Lung ca. NCI-N417                6.0
Lung ca. LX-1                    0.0
Lung ca. NCI-H146                1.6
Lung ca. SHP-77                  95.3
Lung ca. A549                    10.7
Lung ca. NCI-H526                0.0
Lung ca. NCI-H23                 50.0
Lung ca. NCI-H460                12.2
Lung ca. HOP-62                  1.9
Lung ca. NCI-H522                87.7
Liver                            0.2
Fetal Liver                      12.1
Liver ca. HepG2                  0.0
Kidney Pool                      13.0
Fetal Kidney                     44.8
Renal ca. 786-0                  29.9
Renal ca. A498                   6.8
Renal ca. ACHN                   13.3
Renal ca. UO-31                  10.5
Renal ca. TK-10                  44.8
Bladder                          4.9
Gastric ca. (liver met.) NCI-N87 15.8
Gastric ca. KATO III             32.5
Colon ca. SW-948                 0.9
Colon ca. SW480                  10.2
Colon ca.* (SW480 met) SW620     3.8
Colon ca. HT29                   0.2
Colon ca. HCT-116                7.0
Colon ca. CaCo-2                 1.0
Colon cancer tissue              3.8
Colon ca. SW1116                 3.0
Colon ca. Colo-205               0.7
Colon ca. SW-48                  0.0
Colon Pool                       12.3
Small Intestine Pool             9.7
Stomach Pool                     6.6
Bone Marrow Pool                 4.3
Fetal Heart                      3.5
Heart Pool                       4.6
Lymph Node Pool                  3.9
Fetal Skeletal Muscle            10.9
Skeletal Muscle Pool             3.1
Spleen Pool                      4.6
Thymus Pool                      11.3
CNS cancer (glio/astro) U87-MG   15.8
CNS cancer (glio/astro)          83.5
U-118-MG
CNS cancer (neuro; met)          100.0
SK-N-AS
CNS cancer (astro) SF-539        11.7
CNS cancer (astro) SNB-75        46.3
CNS cancer (glio) SNB-19         2.8
CNS cancer (glio) SF-295         20.9
Brain (Amygdala) Pool            21.3
Brain (cerebellum)               54.7
Brain (fetal)                    16.2
Brain (Hippocampus) Pool         24.5
Cerebral Cortex Pool             27.7
Brain (Substantia nigra) Pool    24.5
Brain (Thalamus) Pool            31.0
Brain (whole)                    17.3
Spinal Cord Pool                 29.5
Adrenal Gland                    9.2
Pituitary gland Pool             5.2
Salivary Gland                   2.2
Thyroid (female)                 27.5
Pancreatic ca. CAPAN2            30.1
Pancreas Pool                    11.1

[0871]

TABLE TC
Panel 4.1D
                                 Rel. Exp. (%)
                                 Ag5037, Run
Tissue Name                      223737388
Secondary Th1 act                2.0
Secondary Th2 act                0.0
Secondary Tr1 act                0.0
Secondary Th1 rest               0.6
Secondary Th2 rest               3.6
Secondary Tr1 rest               0.0
Primary Th1 act                  0.0
Primary Th2 act                  2.1
Primary Tr1 act                  2.6
Primary Th1 rest                 4.1
Primary Th2 rest                 3.0
Primary Tr1 rest                 0.0
CD45RA CD4 lymphocyte act        2.8
CD45RO CD4 lymphocyte act        0.0
CD8 lymphocyte act               2.1
Secondary CD8 lymphocyte         2.0
rest
Secondary CD8 lymphocyte         0.0
act
CD4 lymphocyte none              1.8
2ry Thl/Th2/Trl_anti-CD95        0.0
CH11
LAK cells rest                   9.2
LAK cells IL-2                   2.6
LAK cells IL-2 + IL-12           3.8
LAK cells IL-2 + IFN gamma       1.9
LAK cells IL-2 + IL-18           2.1
LAK cells PMA/ionomycin          2.0
NK Cells IL-2 rest               1.1
Two Way MLR 3 day                3.6
Two Way MLR 5 day                5.2
Two Way MLR 7 day                1.9
PBMC rest                        0.0
PBMC PWM                         1.1
PBMC PHA-L                       7.0
Ramos (B cell) none              71.2
Ramos (B cell) ionomycin         100.0
B lymphocytes PWM                2.6
B lymphocytes CD40L and          5.6
IL-4
EOL-1 dbcAMP                     2.0
EOL-1 dbcAMP                     0.0
PMA/ionomycin
Dendritic cells none             7.4
Dendritic cells LPS              2.4
Dendritic cells anti-CD40        5.6
Monocytes rest                   0.5
Monocytes LPS                    0.0
Macrophages rest                 6.8
Macrophages LPS                  1.7
HUVEC none                       3.2
HUVEC starved                    5.0
HUVEC IL-1beta                   7.9
HUVEC IFN gamma                  4.7
HUVEC TNF alpha + IFN gamma      1.0
HUVEC TNF alpha + IL4            2.1
HUVEC IL-11                      2.1
Lung Microvascular EC none       21.6
Lung Microvascular EC TNFalpha + 4.2
IL-1beta
Microvascular Dermal EC none     1.5
Microsvasular Dermal EC TNFalpha + 0.0
IL-lbeta
Bronchial epithelium TNFalpha +  1.1
IL1beta
Small airway epithelium none     5.3
Small airway epithelium TNFalpha + 3.2
IL-lbeta
(Coronery artery SMC rest        4.3
Coronery artery SMC TNFalpha +   5.4
IL-1beta
Astrocytes rest                  5.6
Astrocytes TNFalpha + IL-1beta   3.6
KU-812 (Basophil) rest           3.2
KU-812 (Basophil) PMA/ionomycin  1.2
CCD1106 (Keratinocytes) none     5.4
CCD1106 (Keratinocytes) TNFalpha + 2.7
IL-lbeta
Liver cirrhosis                  6.9
NCI-H292 none                    39.0
NCI-H292 IL-4                    29.3
NCI-H292 IL-9                    60.7
NCI-H292 IL-13                   36.6
NCI-H292 IFN gamma               28.1
HPAEC none                       2.1
HPAEC TNF alpha + IL-1 beta      3.1
Lung fibroblast none             8.8
Lung fibroblast TNF alpha + IL-1 3.7
beta
Lung fibroblast IL-4             0.0
Lung fibroblast IL-9             2.2
Lung fibroblast IL-13            8.4
Lung fibroblast IFN gamma        1.1
Dermal fibroblast CCD1070 rest   2.4
Dermal fibroblast CCD1070 TNF    3.6
alpha
Dermal fibroblast CCD1070 IL-1   3.6
beta
Dermal fibroblast IFN gamma      13.1
Dermal fibroblast IL-4           16.7
Dermal Fibroblasts rest          18.2
Neutrophils TNFa + LPS           0.0
Neutrophils rest                 0.0
Colon                            0.9
Lung                             5.9
Thymus                           6.6
Kidney                           54.3

[0872] General_screening_panel_v1.5 Summary: Ag5037 Highest expression of this gene is seen in a brain cancer cell line (CT=29.4). This gene is widely expressed in this panel, with moderate 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.

[0873] Among tissues with metabolic function, this gene is expressed at low but significant levels in pituitary, adipose, adrenal gland, pancreas, thyroid, fetal heart 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.

[0874] In addition, this gene is expressed at much higher levels in fetal lung tissue (CT=31.5) when compared to expression in the adult counterpart (CT=35.2). Thus, expression of this gene may be used to differentiate between the fetal and adult source of these tissue.

[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: Ag5037 Highest expression is seen in a sample derived from ionomycin treated Ramos B cells (CT=30). This gene is widely expressed in this panel with prominent expression also seen in untreated Ramos cells and in a cluster of treated and untreated samples derived from the NCI—H292 cell line.

[0877] U. CG140747-01: Dual Specificity Phosphatase-Like Gene

[0878] Expression of gene CG140747-01 was assessed using the primer-probe set Ag5038, described in Table UA. Results of the RTQ-PCR runs are shown in Tables UB and UC.

TABLE UA
Probe Name Ag5038
				SEQ
			Start	ID
Primers	Sequences	Length	Position	No
Forward	5′-cctggacatatggagcaagat-	21	1672	290
	3′
Probe	TET-5′-actcctgcacagcccagc	26	1697	291
	ctgaacta-3′-TAMRA
Reverse	5′-gttgcacatccctgagtcttt-	21	1726	292
	3′

[0879]

TABLE UB
General_screening_panel_v1.5
                                 Rel. Exp (%)
                                 Ag5038, Run
Tissue Name                      228966907
Adipose                          22.2
Melanoma* Hs688(A).T             11.4
Melanoma* Hs688(B).T             10.9
Melanoma* M14                    40.6
Melanoma* LOXIMVI                20.2
Melanoma* SK-MEL-5               32.3
Squamous cell carcinoma SCC-4    5.0
Testis Pool                      18.3
Prostate ca.* (bone met) PC-3    11.2
Prostate Pool                    9.9
Placenta                         10.7
Uterus Pool                      12.7
Ovarian ca. OVCAR-3              30.8
Ovarian ca. SK-OV-3              54.3
Ovarian ca. OVCAR-4              12.7
Ovarian ca. OVCAR-5              20.3
Ovarian ca. IGROV-1              15.3
Ovarian ca. OVCAR-8              6.7
Ovary                            7.9
Breast ca. MCF-7                 8.1
Breast ca. MDA-MB-231            28.1
Breast ca. BT 549                31.4
Breast ca. T47D                  15.8
Breast ca. MDA-N                 8.7
Breast Pool                      4.6
Trachea                          14.7
Lung                             2.4
Fetal Lung                       83.5
Lung ca. NCI-N417                2.8
Lung ca. LX-1                    24.0
Lung ca. NCI-H146                9.6
Lung ca. SHP-77                  13.3
Lung ca. A549                    17.4
Lung ca. NCI-H526                11.7
Lung ca. NCI-H23                 22.5
Lung ca. NCI-H460                7.3
Lung ca. HOP-62                  12.0
Lung ca. NCI-H522                16.8
Liver                            1.7
Fetal Liver                      12.9
Liver ca. HepG2                  8.1
Kidney Pool                      17.9
Fetal Kidney                     20.4
Renal ca. 786-0                  28.7
Renal ca. A498                   24.7
Renal ca. ACHN                   33.9
Renal ca. UO-31                  20.7
Renal ca. TK-10                  37.6
Bladder                          21.9
Gastric ca. (liver met.) NCI-N87 32.1
Gastric ca. KATO III             29.9
Colon ca. SW-948                 4.3
Colon ca. SW480                  31.0
Colon ca.* (SW480 met) SW620     21.8
Colon ca. HT29                   7.1
Colon ca. HCT-116                23.5
Colon ca. CaCo-2                 36.3
Colon cancer tissue              9.7
Colon ca. SW1116                 3.7
Colon ca. Colo-205               7.1
Colon ca. SW-48                  5.9
Colon Pool                       13.9
Small Intestine Pool             10.3
Stomach Pool                     6.5
Bone Marrow Pool                 7.3
Fetal Heart                      39.8
Heart Pool                       11.3
Lymph Node Pool                  11.5
Fetal Skeletal Muscle            40.3
Skeletal Muscle Pool             100.0
Spleen Pool                      33.9
Thymus Pool                      42.0
CNS cancer (glio/astro) U87-MG   15.6
CNS cancer (glio/astro) U-118-MG 32.5
CNS cancer (neuro; met) SK-N-AS  64.6
CNS cancer (astro) SF-539        16.6
CNS cancer (astro) SNB-75        34.2
CNS cancer (glio) SNB-19         16.8
CNS cancer (glio) SF-295         49.3
Brain (Amygdala) Pool            12.4
Brain (cerebellum)               46.0
Brain (fetal)                    41.2
Brain (Hippocampus) Pool         16.6
Cerebral Cortex Pool             23.3
Brain (Substantia nigra) Pool    14.7
Brain (Thalamus) Pool            22.5
Brain (whole)                    19.2
Spinal Cord Pool                 15.8
Adrenal Gland                    14.8
Pituitary gland Pool             5.0
Salivary Gland                   5.9
Thyroid (female)                 5.4
Pancreatic ca. CAPAN2            12.0
Pancreas Pool                    16.7

[0880]

TABLE UC
Panel 4.1D
                                 Rel. Exp. (%)
                                 Ag5038, Run
Tissue Name                      223742477
Secondary Th1 act                5.8
Secondary Th2 act                5.4
Secondary Tr1 act                5.7
Secondary Th1 rest               3.4
Secondary Th2 rest               5.6
Secondary Tr1 rest               3.1
Primary Th1 act                  3.2
Primary Th2 act                  5.7
Primary Tr1 act                  4.4
Primary Th1 rest                 3.8
Primary Th2 rest                 2.3
Primary Tr1 rest                 11.6
CD45RA CD4 lymphocyte act        4.5
CD45RO CD4 lymphocyte act        7.5
CD8 lymphocyte act               4.5
Secondary CD8 lymphocyte rest    6.2
Secondary CD8 lymphocyte act     2.5
CD4 lymphocyte none              6.6
2ry Th1/Th2/Tr1_anti-CD95 CH11   5.4
LAK cells rest                   5.8
LAK cells IL-2                   7.1
LAK cells IL-2 + IL-12           3.6
LAK cells IL-2 + IFN gamma       4.7
LAK cells IL-2 + IL-18           5.6
LAK cells PMA/ionomycin          1.6
NK Cells IL-2 rest               11.6
Two Way MLR 3 day                8.2
Two Way MLR 5 day                4.6
Two Way MLR 7 day                4.2
PBMC rest                        5.7
PBMC PWM                         3.5
PBMC PHA-L                       5.1
Ramos (B cell) none              4.8
Ramos (B cell) ionomycin         7.7
B lymphocytes PWM                5.3
B lymphocytes CD40L and IL-4     10.4
EOL-1 dbcAMP                     10.2
EOL-1 dbcAMP PMA/ionomycin       2.9
Dendritic cells none             3.5
Dendritic cells LPS              3.4
Dendritic cells anti-CD40        4.0
Monocytes rest                   26.2
Monocytes LPS                    8.2
Macrophages rest                 5.6
Macrophages LPS                  1.3
HUVEC none                       3.7
HUVEC starved                    7.2
HUVEC IL-1beta                   11.0
HUVEC IFN gamma                  5.9
HUVEC TNF alpha + IFN gamma      3.5
HUVEC TNF alpha + IL4            5.1
HUVEC IL-11                      5.8
Lung Microvascular EC none       7.7
Lung Microvascular EC TNFalpha + IL-1beta 5.2
Microvascular Dermal EC none     4.4
Microsvasular Dermal EC TNFalpha + IL-1beta 5.3
Bronchial epithelium TNFalpha + IL1beta 3.1
Small airway epithelium none     1.6
Small airway epithelium TNFalpha + IL-1beta 4.2
Coronery artery SMC rest         2.9
Coronery artery SMC TNFalpha + IL-1beta 3.2
Astrocytes rest                  1.4
Astrocytes TNFalpha + IL-1beta   1.1
KU-812 (Basophil) rest           1.1
KU-812 (Basophil) PMA/ionomycin  1.0
CCD1106 (Keratinocytes) none     3.8
CCD1106 (Keratinocytes) TNFalpha + IL-1beta 2.6
Liver cirrhosis                  2.3
NCI-H292 none                    2.7
NCI-H292 IL-4                    4.1
NCI-H292 IL-9                    5.0
NCI-H292 IL-13                   5.0
NCI-H292 IFN gamma               2.7
HPAEC none                       4.8
HPAEC TNF alpha + IL-1 beta      19.9
Lung fibroblast none             6.1
Lung fibroblast TNF alpha + IL-1 beta 6.7
Lung fibroblast IL-4             1.4
Lung fibroblast IL-9             2.7
Lung fibroblast IL-13            1.6
Lung fibroblast IFN gamma        2.0
Dermal fibroblast CCD1070 rest   2.4
Dermal fibroblast CCD1070 TNF alpha 8.1
Dermal fibroblast CCD1070 IL-1 beta 1.4
Dermal fibroblast IFN gamma      1.8
Dermal fibroblast IL-4           6.0
Dermal Fibroblasts rest          2.4
Neutrophils TNFa + LPS           13.5
Neutrophils rest                 100.0
Colon                            0.9
Lung                             3.1
Thymus                           14.1
Kidney                           4.4

[0881] General_screening_panel_v1.5 Summary: Ag5038 Highest expression is seen in skeletal muscle (CT=26). In addition, moderate levels of expression are seen in pancreas, thyroid, adrenal, pituitary, adipose, fetal skeletal muscle and adult and fetal liver 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.

[0882] In addition, this gene is expressed at much higher levels in fetal lung tissue (CT=26.3) when compared to expression in the adult counterpart (CT=31.4). Thus, expression of this gene may be used to differentiate between the fetal and adult source of this tissue.

[0883] High to moderate levels of expression of this gene are also 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.

[0884] 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.

[0885] Panel 4.1D Summary: Ag5038 Widespread expression of this gene is seen in this panel with highest expression of this gene seen in resting neutrophils (CT=25). This expression is reduced in neutrophils activated by TNF-alpha+LPS. This expression profile suggests that the protein encoded by this gene is produced by resting neutrophils but not by activated neutrophils. Therefore, the gene product may reduce activation of these inflammatory cells and be useful as a protein therapeutic to reduce or eliminate the symptoms in patients with Crohn's disease, ulcerative colitis, multiple sclerosis, chronic obstructive pulmonary disease, asthma, emphysema, rheumatoid arthritis, lupus erythematosus, or psoriasis. In addition, small molecule or antibody antagonistsof this gene product may be effective in increasing the immune response in patients with AIDS or other immunodeficiencies.

[0886] V. CG141137-01: Long-Chain Acyl-coA Thioesterase 2-Like Gene

[0887] Expression of gene CG141137-01 was assessed using the primer-probe set Ag5044, described in Table VA. Results of the RTQ-PCR runs are shown in Tables VB, VC and VD.

TABLE VA
Probe Name Ag5044
			Start	SEQ
Primers	Sequences	Length	Position	ID No
Forward	5′-cattctaaggcccaggtagatg-	22	1153	293
	3′
Probe	TET-5′-caaacacctgggaggtac	26	1203	294
	ccagaaaa-3′-TAMRA
Reverse	5′-cgcattacaatttagggaaagc-	22	1231	295
	3′

[0888]

TABLE VB
CNS_neurodegeneration_v1.0
                               Rel. Exp. (%)
                               Ag5044, Run
Tissue Name                    224757508
AD 1 Hippo                     17.9
AD 2 Hippo                     21.2
AD 3 Hippo                     10.3
AD 4 Hippo                     3.2
AD 5 hippo                     95.9
AD 6 Hippo                     38.2
Control 2 Hippo                14.1
Control 4 Hippo                4.8
Control (Path) 3 Hippo         0.0
AD 1 Temporal Ctx              7.7
AD 2 Temporal Ctx              34.2
AD 3 Temporal Ctx              5.1
AD 4 Temporal Ctx              14.4
AD 5 Inf Temporal Ctx          100.0
AD 5 SupTemporal Ctx           38.4
AD 6 Inf Temporal Ctx          55.9
AD 6 Sup Temporal Ctx          77.4
Control 1 Temporal Ctx         3.9
Control 2 Temporal Ctx         30.8
Control 3 Temporal Ctx         18.7
Control 4 Temporal Ctx         10.4
Control (Path) 1 Temporal Ctx  75.3
Control (Path) 2 Temporal Ctx  21.9
Control (Path) 3 Temporal Ctx  4.2
Control (Path) 4 Temporal Ctx  32.3
AD 1 Occipital Ctx             18.0
AD 2 Occipital Ctx (Missing)   0.0
AD 3 Occipital Ctx             3.3
AD 4 Occipital Ctx             10.0
AD 5 Occipital Ctx             18.8
AD 6 Occipital Ctx             44.1
Control 1 Occipital Ctx        4.2
Control 2 Occipital Ctx        68.8
Control 3 Occipital Ctx        24.3
Control 4 Occipital Ctx        5.1
Control (Path) 1 Occipital Ctx 72.2
Control (Path) 2 Occipital Ctx 19.3
Control (Path) 3 Occipital Ctx 0.0
Control (Path) 4 Occipital Ctx 16.7
Control 1 Parietal Ctx         5.9
Control 2 Parietal Ctx         35.1
Control 3 Parietal Ctx         31.0
Control (Path) 1 Parietal Ctx  88.3
Control (Path) 2 Parietal Ctx  23.7
Control (Path) 3 Parietal Ctx  4.5
Control (Path) 4 Parietal Ctx  38.7

[0889]

TABLE VC
General_screening_panel_v1.5
                                 Rel. Exp. (%)
                                 Ag5044, Run
Tissue Name                      228969278
Adipose                          0.0
Melanoma* Hs688(A).T             2.4
Melanoma* Hs688(B).T             1.7
Melanoma* M14                    0.3
Melanoma* LOXIMVI                0.0
Melanoma* SK-MEL-5               0.2
Squamous cell carcinoma SCC-4    0.7
Testis Pool                      1.4
Prostate ca.* (bone met) PC-3    1.5
Prostate Pool                    0.8
Placenta                         1.8
Uterus Pool                      0.3
Ovarian ca. OVCAR-3              6.2
Ovarian ca. SK-OV-3              6.5
Ovarian ca. OVCAR-4              1.0
Ovarian ca. OVCAR-5              23.0
Ovarian ca. IGROV-1              0.0
Ovarian ca. OVCAR-8              100.0
Ovary                            1.7
Breast ca. MCF-7                 24.5
Breast ca. MDA-MB-231            3.5
Breast ca. BT 549                2.6
Breast ca. T47D                  10.4
Breast ca. MDA-N                 0.0
Breast Pool                      1.7
Trachea                          1.2
Lung                             0.4
Fetal Lung                       1.7
Lung ca. NCI-N417                0.2
Lung ca. LX-1                    4.1
Lung ca. NCI-H146                0.8
Lung ca. SHP-77                  0.4
Lung ca. A549                    1.5
Lung ca. NCI-H526                1.2
Lung ca. NCI-H23                 1.5
Lung ca. NCI-H460                2.4
Lung ca. HOP-62                  0.8
Lung ca. NCI-H522                3.6
Liver                            0.7
Fetal Liver                      1.6
Liver ca. HepG2                  0.0
Kidney Pool                      4.2
Fetal Kidney                     1.7
Renal ca. 786-0                  0.0
Renal ca. A498                   0.7
Renal ca. ACHN                   1.1
Renal ca. UO-31                  0.7
Renal ca. TK-10                  1.1
Bladder                          1.2
Gastric ca. (liver met.) NCI-N87 5.6
Gastric ca. KATO III             0.0
Colon ca. SW-948                 0.0
Colon ca. SW480                  12.1
Colon ca.* (SW480 met) SW620     3.9
Colon ca. HT29                   1.5
Colon ca. HCT-116                0.0
Colon ca. CaCo-2                 1.8
Colon cancer tissue              0.8
Colon ca. SW1116                 0.0
Colon ca. Colo-205               3.6
Colon ca. SW-48                  2.1
Colon Pool                       1.6
Small Intestine Pool             0.6
Stomach Pool                     0.3
Bone Marrow Pool                 0.3
Fetal Heart                      0.9
Heart Pool                       0.9
Lymph Node Pool                  1.1
Fetal Skeletal Muscle            0.7
Skeletal Muscle Pool             1.9
Spleen Pool                      0.2
Thymus Pool                      0.9
CNS cancer (glio/astro) U87-MG   0.0
CNS cancer (glio/astro) U-118-MG 0.7
CNS cancer (neuro; met) SK-N-AS  1.3
CNS cancer (astro) SF-539        0.5
CNS cancer (astro) SNB-75        3.1
CNS cancer (glio) SNB-19         0.0
CNS cancer (glio) SF-295         0.0
Brain (Amygdala) Pool            5.0
Brain (cerebellum)               26.2
Brain (fetal)                    5.9
Brain (Hippocampus) Pool         5.3
Cerebral Cortex Pool             6.8
Brain (Substantia nigra) Pool    4.0
Brain (Thalamus) Pool            7.3
Brain (whole)                    6.1
Spinal Cord Pool                 1.7
Adrenal Gland                    1.3
Pituitary gland Pool             0.4
Salivary Gland                   0.3
Thyroid (female)                 1.2
Pancreatic ca. CAPAN2            12.0
Pancreas Pool                    1.8

[0890]

TABLE VD
Panel 4.1D
                                 Rel. Exp. (%)
                                 Ag5044, Run
Tissue Name                      223785177
Secondary Th1 act                0.5
Secondary Th2 act                0.7
Secondary Tr1 act                1.0
Secondary Th1 rest               0.3
Secondary Th2 rest               0.0
Secondary Tr1 rest               0.0
Primary Th1 act                  0.0
Primary Th2 act                  0.4
Primary Tr1 act                  2.0
Primary Th1 rest                 0.0
Primary Th2 rest                 0.0
Primary Tr1 rest                 0.7
CD45RA CD4 lymphocyte act        1.2
CD45RO CD4 lymphocyte act        1.8
CD8 lymphocyte act               2.3
Secondary CD8 lymphocyte rest    2.0
Secondary CD8 lymphocyte act     1.6
CD4 lymphocyte none              0.3
2ry Th1/Th2/Tr1_anti-CD95 CH11   0.2
LAK cells rest                   0.9
LAK cells IL-2                   1.5
LAK cells IL-2 + IL-12           1.0
LAK cells IL-2 + IFN gamma       1.2
LAK cells IL-2 + IL-18           1.1
LAK cells PMA/ionomycin          1.1
NK Cells IL-2 rest               2.1
Two Way MLR 3 day                2.3
Two Way MLR 5 day                1.4
Two Way MLR 7 day                1.7
PBMC rest                        0.5
PBMC PWM                         0.5
PBMC PHA-L                       0.8
Ramos (B cell) none              0.0
Ramos (B cell) ionomycin         0.0
B lymphocytes PWM                1.5
B lymphocytes CD40L and IL-4     0.4
EOL-1 dbcAMP                     0.0
EOL-1 dbcAMP PMA/ionomycin       0.0
Dendritic cells none             2.1
Dendritic cells LPS              0.5
Dendritic cells anti-CD40        1.5
Monocytes rest                   0.0
Monocytes LPS                    0.2
Macrophages rest                 5.0
Macrophages LPS                  0.6
HUVEC none                       0.0
HUVEC starved                    0.3
HUVEC IL-1beta                   0.2
HUVEC IFN gamma                  1.2
HUVEC TNF alpha + IFN gamma      0.3
HUVEC TNF alpha + IL4            0.5
HUVEC IL-11                      0.5
Lung Microvascular EC none       0.7
Lung Microvascular EC TNFalpha + IL-1beta 2.1
Microvascular Dermal EC none     0.0
Microsvasular Dermal EC TNFalpha + IL-1beta 1.0
Bronchial epithelium TNFalpha + IL1beta 0.0
Small airway epithelium none     0.0
Small airway epithelium TNFalpha + IL-1beta 0.0
Coronery artery SMC rest         0.0
Coronery artery SMC TNFalpha + IL-1beta 0.2
Astrocytes rest                  0.6
Astrocytes TNFalpha + IL-1beta   0.8
KU-812 (Basophil) rest           0.2
KU-812 (Basophil) PMA/ionomycin  1.3
CCD1106 (Keratinocytes) none     1.9
CCD1106 (Keratinocytes) TNFalpha + IL-1beta 1.0
Liver cirrhosis                  0.2
NCI-H292 none                    4.4
NCI-H292 IL-4                    5.1
NCI-H292 IL-9                    6.4
NCI-H292 IL-13                   3.3
NCI-H292 IFN gamma               3.2
HPAEC none                       0.4
HPAEC TNF alpha + IL-1 beta      0.0
Lung fibroblast none             0.2
Lung fibroblast TNF alpha + IL-1 beta 0.8
Lung fibroblast IL-4             1.7
Lung fibroblast IL-9             0.4
Lung fibroblast IL-13            0.0
Lung fibroblast IFN gamma        0.7
Dermal fibroblast CCD1070 rest   0.7
Dermal fibroblast CCD1070 TNF alpha 4.0
Dermal fibroblast CCD1070 IL-1 beta 1.1
Dermal fibroblast IFN gamma      3.3
Dermal fibroblast IL-4           0.2
Dermal Fibroblasts rest          2.0
Neutrophils TNFa + LPS           0.3
Neutrophils rest                 2.9
Colon                            7.3
Lung                             8.2
Thymus                           25.7
Kidney                           100.0

[0891] CNS_neurodegeneration_v1.0 Summary: Ag5044 This panel does not show differential expression of this gene in Alzheimer's disease. However, this profile confirms the expression of this gene at moderate levels in the brain. Please see Panel 1.5 for discussion of utility of this gene in the central nervous system.

[0892] General_screening_panel_v1.5 Summary: Ag5044 Highest expression of this gene is seen in an ovarian cancer cell line (CT=30). 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 ovarian cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of ovarian cancer.

[0893] This gene is also expressed at low but significant levels in all regions of the CNS examined, 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 neurological disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.

[0894] Panel 4.1D Summary: Ag5044 Highest expression of this gene is seen in kidney (CT=30.5). 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.

[0895] W. CG141240-01: ATP Synthase F Chain, Mitochondrial-Like Gene

[0896] Expression of gene CG141240-01 was assessed using the primer-probe set Ag5045, described in Table WA. Results of the RTQ-PCR runs are shown in Tables WB and WC.

TABLE WA
Probe Name Ag5045
			Start	SEQ
Primers	Sequences	Length	Position	ID No
Forward	5′-gcagggtacatgctcttcatc-	21	253	296
	3′
Probe	TET-5′-cctttcctacaaggagct	26	279	297
	caagcacg-3′-TAMRA
Reverse	5′-gagtgcagagcatgtcttcttc-	22	326	298
	3′

[0897]

TABLE WB
General_screening_panel_v1.5
                                 Rel. Exp. (%)
                                 Ag5045, Run
Tissue Name                      228969281
Adipose                          24.3
Melanoma* Hs688(A).T             1.2
Melanoma* Hs688(B).T             1.9
Melanoma* M14                    7.9
Melanoma* LOXIMVI                16.3
Melanoma* SK-MEL-5               33.0
Squamous cell carcinoma SCC-4    6.9
Testis Pool                      12.4
Prostate ca.* (bone met) PC-3    40.9
Prostate Pool                    10.2
Placenta                         0.9
Uterus Pool                      5.8
Ovarian ca. OVCAR-3              80.1
Ovarian ca. SK-OV-3              21.8
Ovarian ca. OVCAR-4              1.6
Ovarian ca. OVCAR-5              61.6
Ovarian ca. IGROV-1              11.7
Ovarian ca. OVCAR-8              15.8
Ovary                            4.7
Breast ca. MCF-7                 59.9
Breast ca. MDA-MB-231            45.4
Breast ca. BT 549                28.3
Breast ca. T47D                  5.0
Breast ca. MDA-N                 7.1
Breast Pool                      13.2
Trachea                          10.9
Lung                             5.6
Fetal Lung                       17.6
Lung ca. NCI-N417                4.0
Lung ca. LX-1                    39.2
Lung ca. NCI-H146                5.7
Lung ca. SHP-77                  21.5
Lung ca. A549                    27.9
Lung ca. NCI-H526                4.1
Lung ca. NCI-H23                 32.1
Lung ca. NCI-H460                30.6
Lung ca. HOP-62                  24.8
Lung ca. NCI-H522                54.3
Liver                            0.0
Fetal Liver                      15.9
Liver ca. HepG2                  10.5
Kidney Pool                      32.3
Fetal Kidney                     100.0
Renal ca. 786-0                  16.7
Renal ca. A498                   4.6
Renal ca. ACHN                   18.9
Renal ca. UO-31                  9.0
Renal ca. TK-10                  23.2
Bladder                          24.0
Gastric ca. (liver met.) NCI-N87 30.8
Gastric ca. KATO III             22.8
Colon ca. SW-948                 5.6
Colon ca. SW480                  21.6
Colon ca.* (SW480 met) SW620     42.3
Colon ca. HT29                   9.3
Colon ca. HCT-116                75.3
Colon ca. CaCo-2                 28.7
Colon cancer tissue              13.0
Colon ca. SW1116                 8.1
Colon ca. Colo-205               5.9
Colon ca. SW-48                  4.8
Colon Pool                       12.6
Small Intestine Pool             16.8
Stomach Pool                     14.2
Bone Marrow Pool                 21.0
Fetal Heart                      12.9
Heart Pool                       5.9
Lymph Node Pool                  25.0
Fetal Skeletal Muscle            7.2
Skeletal Muscle Pool             7.2
Spleen Pool                      12.9
Thymus Pool                      28.5
CNS cancer (glio/astro) U87-MG   33.0
CNS cancer (glio/astro) U-118-MG 29.1
CNS cancer (neuro; met) SK-N-AS  57.0
CNS cancer (astro) SF-539        8.0
CNS cancer (astro) SNB-75        31.0
CNS cancer (glio) SNB-19         15.2
CNS cancer (glio) SF-295         93.3
Brain (Amygdala) Pool            2.6
Brain (cerebellum)               7.9
Brain (fetal)                    14.6
Brain (Hippocampus) Pool         2.2
Cerebral Cortex Pool             6.9
Brain (Substantia nigra) Pool    3.3
Brain (Thalamus) Pool            8.0
Brain (whole)                    1.3
Spinal Cord Pool                 6.7
Adrenal Gland                    0.0
Pituitary gland Pool             1.5
Salivary Gland                   1.4
Thyroid (female)                 2.3
Pancreatic ca. CAPAN2            25.2
Pancreas Pool                    28.7

[0898]

TABLE WC
Panel 4.1D
                                 Rel. Exp. (%)
                                 Ag5045, Run
Tissue Name                      223784809
Secondary Th1 act                11.2
Secondary Th2 act                11.8
Secondary Tr1 act                15.6
Secondary Th1 rest               9.7
Secondary Th2 rest               8.5
Secondary Tr1 rest               12.2
Primary Th1 act                  8.1
Primary Th2 act                  12.9
Primary Tr1 act                  13.0
Primary Th1 rest                 8.5
Primary Th2 rest                 9.2
Primary Tr1 rest                 5.8
CD45RA CD4 lymphocyte act        11.1
CD45RO CD4 lymphocyte act        12.7
CD8 lymphocyte act               18.7
Secondary CD8 lymphocyte rest    6.4
Secondary CD8 lymphocyte act     11.3
CD4 lymphocyte none              4.0
2ry Th1/Th2/Tr1_anti-CD95 CH11   15.8
LAK cells rest                   12.0
LAK cells IL-2                   8.4
LAK cells IL-2 + IL-12           5.8
LAK cells IL-2 + IFN gamma       10.7
LAK cells IL-2 + IL-18           21.6
LAK cells PMA/ionomycin          9.2
NK Cells IL-2 rest               22.5
Two Way MLR 3 day                18.6
Two Way MLR 5 day                12.0
Two Way MLR 7 day                7.6
PBMC rest                        2.3
PBMC PWM                         12.6
PBMC PHA-L                       11.7
Ramos (B cell) none              26.4
Ramos (B cell) ionomycin         26.6
B lymphocytes PWM                13.5
B lymphocytes CD40L and IL-4     32.5
EOL-1 dbcAMP                     23.7
EOL-1 dbcAMP PMA/ionomycin       20.0
Dendritic cells none             1.6
Dendritic cells LPS              9.1
Dendritic cells anti-CD40        8.5
Monocytes rest                   17.2
Monocytes LPS                    27.5
Macrophages rest                 6.0
Macrophages LPS                  2.8
HUVEC none                       3.2
HUVEC starved                    4.8
HUVEC IL-1beta                   2.5
HUVEC IFN gamma                  12.3
HUVEC TNF alpha + IFN gamma      6.0
HUVEC TNF alpha + IL4            2.6
HUVEC IL-11                      3.3
Lung Microvascular EC none       12.7
Lung Microvascular EC TNFalpha + IL-1beta 5.9
Microvascular Dermal EC none     3.6
Microsvasular Dermal EC TNFalpha + IL-1beta 4.6
Bronchial epithelium TNFalpha + IL1beta 8.7
Small airway epithelium none     1.0
Small airway epithelium TNFalpha + IL-1beta 1.9
Coronery artery SMC rest         5.4
Coronery artery SMC TNFalpha + IL-1beta 4.7
Astrocytes rest                  5.5
Astrocytes TNFalpha + IL-1beta   4.5
KU-812 (Basophil) rest           17.6
KU-812 (Basophil) PMA/ionomycin  19.6
CCD1106 (Keratinocytes) none     5.4
CCD1106 (Keratinocytes) TNFalpha + IL-1beta 2.1
Liver cirrhosis                  0.6
NCI-H292 none                    7.9
NCI-H292 IL-4                    14.0
NCI-H292 IL-9                    12.5
NCI-H292 IL-13                   12.2
NCI-H292 IFN gamma               6.2
HPAEC none                       7.3
HPAEC TNF alpha + IL-1 beta      7.4
Lung fibroblast none             5.4
Lung fibroblast TNF alpha + IL-1 beta 2.2
Lung fibroblast IL-4             5.3
Lung fibroblast IL-9             6.0
Lung fibroblast IL-13            3.9
Lung fibroblast IFN gamma        1.4
Dermal fibroblast CCD1070 rest   8.9
Dermal fibroblast CCD1070 TNF alpha 12.9
Dermal fibroblast CCD1070 IL-1 beta 4.0
Dermal fibroblast IFN gamma      7.2
Dermal fibroblast IL-4           6.2
Dermal Fibroblasts rest          3.0
Neutrophils TNFa + LPS           2.5
Neutrophils rest                 10.4
Colon                            3.1
Lung                             5.3
Thymus                           30.4
Kidney                           100.0

[0899] General_screening_panel_v1.5 Summary: Ag5045 This gene is widely expressed in this panel, with highest expression in kidney (CT=29.4). This gene is widely expressed in this panel, with moderate 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.

[0900] Among tissues with metabolic function, this gene is expressed at moderate to low levels in adipose, 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.

[0901] 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.

[0902] Panel 4.1D Summary: Ag5045 Highest expression of this gene is seen in the kidney (CT=30.1). This gene is widely expressed at low but significant levels in many samples on this panel, including samples derived from B cells, T cells and lung and dermal fibroblasts. 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.

[0903] X. CG141355-01 and CG141355-02: GTPASE RAB37-Like Gene

[0904] Expression of gene CG141355-01 and full-length physical clone CG141355-02 was assessed using the primer-probe set Ag5048, described in Table XA. Results of the RTQ-PCR runs are shown in Tables XB, XC and XD. Please note that CG141355-02 represents a full-length physical clone of the CG141355-01 gene, validating the prediction of the gene sequence.

TABLE XA
Probe Name Ag5048
			Start	SEQ
Primers	Sequences	Length	Position	ID No
Forward	5′-atcgccaaggaactgaaatac-	21	619	299
	3′
Probe	TET-5′-agcccagcttccagatc	24	662	300
	cgagact-3′-TAMRA
Reverse	5′-cgcttcttctgggactctaca	22	686	301
	t-3′

[0905]

TABLE XB
General_screening panel_v1.5
                                 Rel. Exp. (%)
                                 Ag5048, Run
Tissue Name                      228969347
Adipose                          3.5
Melanoma* Hs688(A).T             0.0
Melanoma* Hs688(B).T             0.0
Melanoma* M14                    0.0
Melanoma* LOXIMVI                0.0
Melanoma* SK-MEL-5               1.5
Squamous cell carcinoma SCC-4    0.4
Testis Pool                      0.6
Prostate ca.* (bone met) PC-3    2.7
Prostate Pool                    4.6
Placenta                         3.1
Uterus Pool                      2.0
Ovarian ca. OVCAR-3              0.8
Ovarian ca. SK-OV-3              0.0
Ovarian ca. OVCAR-4              0.0
Ovarian ca. OVCAR-5              52.9
Ovarian ca. IGROV-1              0.9
Ovarian ca. OVCAR-8              0.6
Ovary                            2.2
Breast ca. MCF-7                 3.5
Breast ca. MDA-MB-231            3.9
Breast ca. BT 549                0.4
Breast ca. T47D                  2.4
Breast ca. MDA-N                 0.0
Breast Pool                      3.8
Trachea                          7.6
Lung                             0.2
Fetal Lung                       12.1
Lung ca. NCI-N417                0.0
Lung ca. LX-1                    6.5
Lung ca. NCI-H146                0.0
Lung ca. SHP-77                  0.0
Lung ca. A549                    46.3
Lung ca. NCI-H526                0.5
Lung ca. NCI-H23                 6.2
Lung ca. NCI-H460                0.3
Lung ca. HOP-62                  6.0
Lung ca. NCI-H522                6.5
Liver                            4.5
Fetal Liver                      13.2
Liver ca. HepG2                  2.7
Kidney Pool                      4.8
Fetal Kidney                     0.5
Renal ca. 786-0                  0.4
Renal ca. A498                   2.6
Renal ca. ACHN                   0.0
Renal ca. UO-31                  0.2
Renal ca. TK-10                  3.4
Bladder                          2.9
Gastric ca. (liver met.) NCI-N87 5.0
Gastric ca. KATO III             0.8
Colon ca. SW-948                 0.2
Colon ca. SW480                  2.0
Colon ca.* (SW480 met) SW620     5.2
Colon ca. HT29                   2.0
Colon ca. HCT-116                18.3
Colon ca. CaCo-2                 100.0
Colon cancer tissue              8.0
Colon ca. SW1116                 0.6
Colon ca. Colo-205               2.0
Colon ca. SW-48                  4.9
Colon Pool                       3.4
Small Intestine Pool             1.4
Stomach Pool                     1.6
Bone Marrow Pool                 2.5
Fetal Heart                      0.8
Heart Pool                       2.3
Lymph Node Pool                  3.0
Fetal Skeletal Muscle            0.6
Skeletal Muscle Pool             1.7
Spleen Pool                      14.6
Thymus Pool                      8.4
CNS cancer (glio/astro) U87-MG   0.6
CNS cancer (glio/astro) U-118-MG 1.0
CNS cancer (neuro; met) SK-N-AS  0.2
CNS cancer (astro) SF-539        0.0
CNS cancer (astro) SNB-75        0.3
CNS cancer (glio) SNB-19         0.9
CNS cancer (glio) SF-295         0.2
Brain (Amygdala) Pool            9.0
Brain (cerebellum)               95.3
Brain (fetal)                    0.8
Brain (Hippocampus) Pool         6.7
Cerebral Cortex Pool             22.1
Brain (Substantia nigra) Pool    12.0
Brain (Thalamus) Pool            10.8
Brain (whole)                    11.6
Spinal Cord Pool                 6.2
Adrenal Gland                    2.5
Pituitary gland Pool             0.4
Salivary Gland                   0.9
Thyroid (female)                 0.6
Pancreatic ca. CAPAN2            0.0
Pancreas Pool                    3.9

[0906]

TABLE XC
Panel 4.1D
                                 Rel. Exp. (%)
                                 Ag5048, Run
Tissue Name                      223785397
Secondary Th1 act                3.2
Secondary Th2 act                5.3
Secondary Tr1 act                7.4
Secondary Th1 rest               68.3
Secondary Th2 rest               73.2
Secondary Tr1 rest               82.9
Primary Th1 act                  4.7
Primary Th2 act                  6.5
Primary Tr1 act                  8.1
Primary Th1 rest                 44.4
Primary Th2 rest                 82.4
Primary Tr1 rest                 47.0
CD45RA CD4 lymphocyte act        6.9
CD45RO CD4 lymphocyte act        9.8
CD8 lymphocyte act               8.4
Secondary CD8 lymphocyte rest    5.8
Secondary CD8 lymphocyte act     32.3
CD4 lymphocyte none              10.4
2ry Th1/Th2/Tr1_anti-CD95 CH11   100.0
LAK cells rest                   4.1
LAK cells IL-2                   10.2
LAK cells IL-2 + IL-12           2.3
LAK cells IL-2 + IFN gamma       7.2
LAK cells IL-2 + IL-18           8.0
LAK cells PMA/ionomycin          2.0
NK Cells IL-2 rest               54.7
Two Way MLR 3 day                2.8
Two Way MLR 5 day                2.9
Two Way MLR 7 day                15.2
PBMC rest                        16.8
PBMC PWM                         0.1
PBMC PHA-L                       3.0
Ramos (B cell) none              2.0
Ramos (B cell) ionomycin         3.7
B lymphocytes PWM                1.6
B lymphocytes CD40L and IL-4     9.0
EOL-1 dbcAMP                     21.6
EOL-1 dbcAMP PMA/ionomycin       0.8
Dendritic cells none             1.3
Dendritic cells LPS              0.6
Dendritic cells anti-CD40        0.6
Monocytes rest                   19.1
Monocytes LPS                    0.4
Macrophages rest                 2.0
Macrophages LPS                  0.0
HUVEC none                       0.0
HUVEC starved                    0.0
HUVEC IL-1beta                   0.2
HUVEC IFN gamma                  0.1
HUVEC TNF alpha + IFN gamma      0.0
HUVEC TNF alpha + IL4            0.0
HUVEC IL-11                      1.0
Lung Microvascular EC none       0.7
Lung Microvascular EC TNFalpha + IL-1beta 0.1
Microvascular Dermal EC none     0.0
Microsvasular Dermal EC TNFalpha + IL-1beta 0.0
Bronchial epithelium TNFalpha + IL1beta 0.0
Small airway epithelium none     0.2
Small airway epithelium TNFalpha + IL-1beta 0.0
Coronery artery SMC rest         0.0
Coronery artery SMC TNFalpha + IL-1beta 0.0
Astrocytes rest                  0.0
Astrocytes TNFalpha + IL-1beta   0.0
KU-812 (Basophil) rest           10.2
KU-812 (Basophil) PMA/ionomycin  15.6
CCD1106 (Keratinocytes) none     0.1
CCD1106 (Keratinocytes) TNFalpha + IL-1beta 0.0
Liver cirrhosis                  0.6
NCI-H292 none                    0.2
NCI-H292 IL-4                    0.3
NCI-H292 IL-9                    0.4
NCI-H292 IL-13                   0.6
NCI-H292 IFN gamma               0.3
HPAEC none                       0.5
HPAEC TNF alpha + IL-1 beta      0.1
Lung fibroblast none             1.0
Lung fibroblast TNF alpha + IL-1 beta 0.5
Lung fibroblast IL-4             0.1
Lung fibroblast IL-9             0.0
Lung fibroblast IL-13            0.0
Lung fibroblast IFN gamma        0.0
Dermal fibroblast CCD1070 rest   3.4
Dermal fibroblast CCD1070 TNF alpha 65.1
Dermal fibroblast CCD1070 IL-1 beta 0.7
Dermal fibroblast IFN gamma      0.9
Dermal fibroblast IL-4           3.0
Dermal Fibroblasts rest          0.5
Neutrophils TNFa + LPS           10.8
Neutrophils rest                 42.3
Colon                            3.0
Lung                             2.9
Thymus                           15.2
Kidney                           2.0

[0907]

TABLE XD
Panel 5 Islet
                                 Rel. Exp. (%)
                                 Ag5048, Run
Tissue Name                      306067452
97457_Patient-02go_adipose       0.0
97476_Patient-07sk_skeletal muscle 0.0
97477_Patient-07ut_uterus        9.5
97478_Patient-07pl_placenta      12.0
99167_Bayer Patient 1            49.7
97482_Patient-08ut_uterus        11.0
97483_Patient-08pl_placenta      3.0
97486_Patient-09sk_skeletal muscle 15.4
97487_Patient-09ut_uterus        8.3
97488_Patient-09pl_placenta      10.8
97492_Patient-10ut_uterus        3.8
97493_Patient-10pl_placenta      10.7
97495_Patient-11go_adipose       8.7
97496_Patient-11sk_skeletal muscle 19.1
97497_Patient-11ut_uterus        33.7
97498_Patient-11pl_placenta      8.2
97500_Patient-12go_adipose       18.7
97501_Patient-12sk_skeletal muscle 23.7
97502_Patient-12ut_uterus        16.6
97503_Patient-12pl_placenta      19.6
94721_Donor 2 U - A_Mesenchymal Stem Cells 5.0
94722_Donor 2 U - B_Mesenchymal Stem Cells 0.0
94723_Donor 2 U - C_Mesenchymal Stem Cells 7.7
94709_Donor 2 AM - A_adipose     2.5
94710_Donor 2 AM - B_adipose     2.4
94711_Donor 2 AM - C_adipose     100.0
94712_Donor 2 AD - A_adipose     9.2
94713_Donor 2 AD - B_adipose     4.2
94714_Donor 2 AD - C_adipose     6.4
94742_Donor 3 U - A_Mesenchymal Stem Cells 7.4
94743_Donor 3 U - B_Mesenchymal Stem Cells 4.7
94730_Donor 3 AM - A_adipose     7.5
94731_Donor 3 AM - B_adipose     6.2
94732_Donor 3 AM - C_adipose     4.5
94733_Donor 3 AD - A_adipose     0.0
94734_Donor 3 AD - B_adipose     0.0
94735_Donor 3 AD - C_adipose     2.3
77138_Liver_HepG2untreated       18.7
73556_Heart_Cardiac stromal cells (primary) 2.7
81735_Small Intestine            8.3
72409_Kidney_Proximal Convoluted Tubule 13.3
82685_Small intestine_Duodenum   10.9
90650_Adrenal_Adrenocortical adenoma 5.6
72410_Kidney_HRCE                0.0
72411_Kidney_HRE                 0.0
73139_Uterus_Uterine smooth muscle cells 2.6

[0908] General_screening_panel_v1.5 Summary: Ag5048 Highest expression is seen in cerebellum and a colon cancer cell line (CTs=27). Prominent expression is also seen in a single ovarian cancer and lung cancer cell line. Thus, expression of this gene could be used to differentiate between the cerebellar and colon cancer cell line sample and other samples on this panel. In addition, this gene may be involved in ovarian, lung, and colon cancers as well as CNS disorders that have the cerebellum as the site of pathology, such as autism and the ataxias.

[0909] Panel 4.1D Summary: Ag5048 Prominent levels of expression are seen in resting primary and secondary T cells, resting neutrophils, TNF-a treated dermal fibroblasts, and resting NK cells. This gene encodes a putative Rab37 molecule that may play an important role in mast cell degranulation. (Masuda ES. FEBS Lett Mar. 17, 2000;470(1):61-4). Thus, based on the expression profile of this protein and the homology to Rab37, modulation of the expression or function of this protein may be useful as a therapeutic intervention in the treatment of allergy, asthma, arthritis, psoriasis, IBD, and lupus, as well as any T-cell mediated disease.

[0910] Panel 5 Islet Summary: Ag5048 Detectable expression of this gene is limited to a single adipose sample (CT=34) in this panel.

[0911] Y. CG142072-02: CATHEPSIN L PRECURSOR

[0912] Expression of full-length physical clone CG142072-02 was assessed using the primer-probe set Ag7053, described in Table YA. Results of the RTQ-PCR runs are shown in Table YB.

TABLE YA
Probe Name Ag7053
			Start	SEQ
Primers	Sequences	Length	Position	ID No
Forward	5′-agttttccggaacactttcc-3′	20	576	302
Probe	TET-5′-tttgaaagccattcatca	26	614	303
	cctgcctg-3′-TAMRA
Reverse	5′-tttggagacatgaccagtgaa-	21	645	304
	3′

[0913]

TABLE YB
General screening panel v1.6
                                 Rel. Exp. (%)
                                 Ag7053, Run
Tissue Name                      282273864
Adipose                          1.2
Melanoma* Hs688(A).T             5.1
Melanoma* Hs688(B).T             5.4
Melanoma* M14                    1.7
Melanoma* LOXIMVI                6.1
Melanoma* SK-MEL-5               36.3
Squamous cell carcinoma SCC-4    0.7
Testis Pool                      1.5
Prostate ca.* (bone met) PC-3    4.3
Prostate Pool                    0.9
Placenta                         4.9
Uterus Pool                      0.4
Ovarian ca. OVCAR-3              2.6
Ovarian ca. SK-OV-3              16.7
Ovarian ca. OVCAR-4              0.7
Ovarian ca. OVCAR-5              3.7
Ovarian ca. IGROV-1              2.8
Ovarian ca. OVCAR-8              2.7
Ovary                            1.1
Breast ca. MCF-7                 3.3
Breast ca. MDA-MB-231            6.7
Breast ca. BT 549                100.0
Breast ca. T47D                  0.4
Breast ca. MDA-N                 0.6
Breast Pool                      1.6
Trachea                          0.8
Lung                             0.8
Fetal Lung                       1.1
Lung ca. NCI-N417                0.0
Lung ca. LX-1                    0.1
Lung ca. NCI-H146                0.0
Lung ca. SHP-77                  0.8
Lung ca. A549                    19.2
Lung ca. NCI-H526                0.0
Lung ca. NCI-H23                 10.7
Lung ca. NCI-H460                21.9
Lung ca. HOP-62                  0.8
Lung ca. NCI-H522                1.3
Liver                            0.6
Fetal Liver                      3.4
Liver ca. HepG2                  0.8
Kidney Pool                      2.7
Fetal Kidney                     1.1
Renal ca. 786-0                  8.2
Renal ca. A498                   6.6
Renal ca. ACHN                   1.2
Renal ca. UO-31                  2.7
Renal ca. TK-10                  5.1
Bladder                          2.4
Gastric ca. (liver met.) NCI-N87 3.3
Gastric ca. KATO III             0.0
Colon ca. SW-948                 0.0
Colon ca. SW480                  0.0
Colon ca.* (SW480 met) SW620     0.3
Colon ca. HT29                   0.2
Colon ca. HCT-116                3.3
Colon ca. CaCo-2                 1.6
Colon cancer tissue              6.9
Colon ca. SW1116                 0.0
Colon ca. Colo-205               0.1
Colon ca. SW-48                  0.1
Colon Pool                       1.6
Small Intestine Pool             0.7
Stomach Pool                     1.2
Bone Marrow Pool                 0.3
Fetal Heart                      0.8
Heart Pool                       0.5
Lymph Node Pool                  1.5
Fetal Skeletal Muscle            0.3
Skeletal Muscle Pool             0.3
Spleen Pool                      1.4
Thymus Pool                      0.9
CNS cancer (glio/astro) U87-MG   21.2
CNS cancer (glio/astro) U-118-MG 25.3
CNS cancer (neuro; met) SK-N-AS  0.5
CNS cancer (astro) SF-539        8.1
CNS cancer (astro) SNB-75        62.9
CNS cancer (glio) SNB-19         2.5
CNS cancer (glio) SF-295         9.1
Brain (Amygdala) Pool            0.8
Brain (cerebellum)               1.3
Brain (fetal)                    0.4
Brain (Hippocampus) Pool         1.1
Cerebral Cortex Pool             0.8
Brain (Substantia nigra) Pool    0.8
Brain (Thalamus) Pool            1.1
Brain (whole)                    0.8
Spinal Cord Pool                 1.0
Adrenal Gland                    1.4
Pituitary gland Pool             0.4
Salivary Gland                   0.9
Thyroid (female)                 0.8
Pancreatic ca. CAPAN2            1.7
Pancreas Pool                    0.5

[0914] General_screening_panel_v1.6 Summary: Ag7053 Highest expression of this gene is detected in breast cancer BT 549 cell line (CT=27.2). High to moderate levels of expression of this gene is also seen in number of cell lines derived from pancreatic, gastric, colon, lung, liver, 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, liver, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers.

[0915] Among tissues with metabolic or endocrine function, this gene is expressed at moderate to low levels in pancreas, adipose, adrenal gland, thyroid, 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.

[0916] In addition, this gene is expressed at low levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, 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.

[0917] Z. CG142102-01: PEPTIDYLPIROLYL ISOMERASE A-Like Gene

[0918] Expression of gene CG142102-01 was assessed using the primer-probe set Ag7410, described in Table ZA.

TABLE ZA
Probe Name Ag7410
			Start	SEQ
Primers	Sequences	Length	Position	ID No
Forward	5′-ctgaaccctcacattcccaa-3′	20	353	305
Probe	TET-5′-ccaattacttatccatgg	26	374	306
	caaatgct-3′-TAMRA
Reverse	5′-tcttggcagtgcagaggaa-3′	19	427	307

[0919] AA. CG57760-02: Prostaglandin-H12 D-isomerase Precursor

[0920] Expression of full-length physical clone CG57760-02 was assessed using the primer-probe set Ag7019, described in Table AAA. Results of the RTQ-PCR runs are shown in Table AAB.

TABLE AAA
Probe Name Ag7019
			Start	SEQ
Primers	Sequences	Length	Position	ID No
Forward	5′-caacttacagcagcgcgta-3′	19	122	308
Probe	TET-5′-agaccgactacgaccag	24	148	309
	tacgcgc-3′-TAMRA
Reverse	5′-ttgctgccctggctgta-3′	17	177	310

[0921]

TABLE AAB
General_screening_panel_v1.6
                                 Rel.Exp. (%)
                                 Ag7019, Run
Tissue Name                      282273670
Adipose                          0.0
Melanoma* Hs688(A).T             0.0
Melanoma* Hs688(B).T             0.0
Melanoma* M14                    0.0
Melanoma* LOXIMVI                0.0
Melanoma* SK-MEL-5               0.0
Squamous cell carcinoma SCC-4    0.0
Testis Pool                      0.0
Prostate ca.* (bone met) PC-3    0.0
Prostate Pool                    0.0
Placenta                         36.6
Uterus Pool                      0.0
Ovarian ca. OVCAR-3              0.0
Ovarian ca. SK-OV-3              0.0
Ovarian ca. OVCAR-4              0.0
Ovarian ca. OVCAR-5              0.0
Ovarian ca. IGROV-1              0.0
Ovarian ca. OVCAR-8              0.0
Ovary                            0.0
Breast ca. MCF-7                 0.0
Breast ca. MDA-MB-231            0.0
Breast ca. BT 549                0.0
Breast ca. T47D                  0.0
Breast ca. MDA-N                 0.0
Breast Pool                      0.0
Trachea                          0.0
Lung                             0.0
Fetal Lung                       0.0
Lung ca. NCI-N417                0.0
Lung ca. LX-1                    0.0
Lung ca. NCI-H146                0.0
Lung ca. SHP-77                  0.0
Lung ca. A549                    0.0
Lung ca. NCI-H526                0.0
Lung ca. NCI-H23                 0.0
Lung ca. NCI-H460                0.0
Lung ca. HOP-62                  0.0
Lung ca. NCI-H522                0.0
Liver                            0.0
Fetal Liver                      0.0
Liver ca. HepG2                  0.0
Kidney Pool                      0.0
Fetal Kidney                     0.0
Renal ca. 786-0                  0.0
Renal ca. A498                   0.0
Renal ca. ACHN                   0.0
Renal ca. UO-31                  0.0
Renal ca. TK-10                  0.0
Bladder                          0.0
Gastric ca. (liver met.) NCI-N87 0.0
Gastric ca. KATO III             0.0
Colon ca. SW-948                 0.0
Colon ca. SW480                  29.3
Colon ca.* (SW480 met) SW620     0.0
Colon ca. HT29                   0.0
Colon ca. HCT-116                0.0
Colon ca. CaCo-2                 0.0
Colon cancer tissue              0.0
Colon ca. SW1116                 0.0
Colon ca. Colo-205               0.0
Colon ca. SW-48                  0.0
Colon Pool                       0.0
Small Intestine Pool             0.0
Stomach Pool                     0.0
Bone Marrow Pool                 0.0
Fetal Heart                      0.0
Heart Pool                       0.0
Lymph Node Pool                  0.0
Fetal Skeletal Muscle            0.0
Skeletal Muscle Pool             0.0
Spleen Pool                      0.0
Thymus Pool                      0.0
CNS cancer (glio/astro) U87-MG   0.0
CNS cancer (glio/astro) U-118-MG 0.0
CNS cancer (neuro; met) SK-N-AS  0.0
CNS cancer (astro) SF-539        0.0
CNS cancer (astro) SNB-75        24.8
CNS cancer (glio) SNB-19         0.0
CNS cancer (glio) SF-295         0.0
Brain (Amygdala) Pool            79.0
Brain (cerebellum)               0.0
Brain (fetal)                    0.0
Brain (Hippocampus) Pool         100.0
Cerebral Cortex Pool             0.0
Brain (Substantia nigra) Pool    0.0
Brain (Thalamus) Pool            27.4
Brain (whole)                    0.0
Spinal Cord Pool                 39.2
Adrenal Gland                    0.0
Pituitary gland Pool             0.0
Salivary Gland                   0.0
Thyroid (female)                 0.0
Pancreatic ca. CAPAN2            0.0
Pancreas Pool                    0.0

[0922] General_screening_panel_v1.6 Summary: Ag7410 Highest expression of this gene is seen in brain (hippocampus; CT=100.0) and brain (amygdala; CT=79.0). In addition, this gene is also expressed at moderate levels a colon cancer cell line (CT=29.3); in brain (thalamus; CT=27.4); in spinal cord (CT=39.2); and a CNS cancer line (CT=24.8). Modulation of this gene product may be useful in the treatment of neurological pathologies and cancer.

[0923] AB. CG59361-01: POTENTIAL PHOSPHOLIPID-TRANSPORTING ATPASE VA-Like Gene

[0924] Expression of gene CG59361-01 was assessed using the primer-probe set Ag733, described in Table ABA. Results of the RTQ-PCR runs are shown in Table ABB.

TABLE ABA
Probe Name Ag733
			Start	SEQ
Primers	Sequences	Length	Position	ID No
Forward	5′-ccctgcagacatggtactactc-3′	22	789	311
Probe	TET-5′-tccactgatccagatgga	26	814	312
	atctgtca-3′-TAMRA
Reverse	5′-ccatcaagaccagaagtctcaa	22	842	313
	-3′

[0925]

TABLE ABB
Panel 1.2
                                 Rel. Exp. (%)
                                 Ag733, Run
Tissue Name                      115165150
Endothelial cells                1.6
Heart (Fetal)                    0.2
Pancreas                         3.3
Pancreatic ca. CAPAN 2           1.0
Adrenal Gland                    2.5
Thyroid                          2.5
Salivary gland                   5.3
Pituitary gland                  3.7
Brain (fetal)                    0.9
Brain (whole)                    1.0
Brain (amygdala)                 0.6
Brain (cerebellum)               0.4
Brain (hippocampus)              1.0
Brain (thalamus)                 0.7
Cerebral Cortex                  0.9
Spinal cord                      1.4
glio/astro U87-MG                1.9
glio/astro U-118-MG              1.6
astrocytoma SW1783               1.0
neuro*; met SK-N-AS              3.3
astrocytoma SF-539               1.4
astrocytoma SNB-75               0.8
glioma SNB-19                    0.5
glioma U251                      0.6
glioma SF-295                    2.2
Heart                            2.1
Skeletal Muscle                  0.9
Bone marrow                      0.5
Thymus                           0.4
Spleen                           0.9
Lymph node                       2.0
Colorectal Tissue                0.2
Stomach                          4.5
Small intestine                  1.0
Colon ca. SW480                  0.0
Colon ca.* SW620 (SW480 met)     0.4
Colon ca. HT29                   0.0
Colon ca. HCT-116                0.5
Colon ca. CaCo-2                 2.4
Colon ca. Tissue (ODO3866)       0.4
Colon ca. HCC-2998               0.9
Gastric ca.* (liver met) NCI-N87 5.7
Bladder                          4.1
Trachea                          100.0
Kidney                           2.1
Kidney (fetal)                   3.2
Renal ca. 786-0                  1.1
Renal ca. A498                   1.7
Renal ca. RXF 393                0.6
Renal ca. ACHN                   0.7
Renal ca. UO-31                  2.1
Renal ca. TK-10                  0.7
Liver                            1.7
Liver (fetal)                    0.7
Liver ca. (hepatoblast) HepG2    0.0
Lung                             8.2
Lung (fetal)                     3.5
Lung ca. (small cell) LX-1       0.8
Lung ca. (small cell) NCI-H69    0.2
Lung ca. (s. cell var.) SHP-77   0.3
Lung ca. (large cell) NCI-H460   1.4
Lung ca. (non-sm. cell) A549     0.9
Lung ca. (non-s. cell) NCI-H23   1.2
Lung ca. (non-s. cell) HOP-62    4.2
Lung ca. (non-s. cl) NCI-H522    1.7
Lung ca. (squam.) SW 900         2.1
Lung ca. (squam.) NCI-H596       0.1
Mammary gland                    1.7
Breast ca.* (pl. ef) MCF-7       0.0
Breast ca.* (pl. ef) MDA-MB-231  1.9
Breast ca.* (pl. ef) T47D        1.0
Breast ca. BT-549                0.8
Breast ca. MDA-N                 1.1
Ovary                            0.5
Ovarian ca. OVCAR-3              0.8
Ovarian ca. OVCAR-4              0.9
Ovarian ca. OVCAR-5              4.4
Ovarian ca. OVCAR-8              0.6
Ovarian ca. IGROV-1              1.1
Ovarian ca. (ascites) SK-OV-3    3.6
Uterus                           1.4
Placenta                         10.1
Prostate                         0.8
Prostate ca.* (bone met) PC-3    0.3
Testis                           1.8
Melanoma Hs688(A).T              1.0
Melanoma* (met) Hs688(B).T       2.8
Melanoma UACC-62                 1.2
Melanoma M14                     0.7
Melanoma LOX IMVI                0.4
Melanoma* (met) SK-MEL-5         2.2

[0926] Panel 1.2 Summary: Ag733 Highest expression is seen in trachea (CT=23.5). Thus, expression of this gene could be used to differentiate between this sample and other samples on this panel and as a marker of this tissue.

[0927] Moderate to low levels of expression are seen in metabolic tissues, including skeletal muscle, thyroid, adrenal, pancreas, and adult and fetal liver 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.

[0928] 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.

[0929] This gene is widely expressed in this panel, with moderate expression also seen in the cancer cell lines on this panel. 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.

[0930] AC. CG59444-01: SA Protein-Like Gene

[0931] Expression of gene CG59444-01 was assessed using the primer-probe set Ag3441, described in Table ACA. Results of the RTQ-PCR runs are shown in Tables ACB, ACC and ACD.

TABLE ACA
Probe Name Ag3441
			Start
Primers	Sequences	Length	Position	SEQ ID No
Forward	5′-caccctacgatgtgcagatt-	20	1337	314
	3′
Probe	TET-5′-caacgtcctgcctcctg	25	1371	315
	gagaagag-3′-TAMRA
Reverse	5′-gatacggacggcaacattc-3′	19	1398	316

[0932]

TABLE ACB
CNS_neurodegeneration_v1.0
                               Rel. Exp. (%)
                               Ag3441, Run
Tissue Name                    210374767
AD 1 Hippo                     20.3
AD 2 Hippo                     52.9
AD 3 Hippo                     5.8
AD 4 Hippo                     23.3
AD 5 hippo                     9.5
AD 6 Hippo                     100.0
Control 2 Hippo                26.8
Control 4 Hippo                68.8
Control (Path) 3 Hippo         6.7
AD 1 Temporal Ctx              26.6
AD 2 Temporal Ctx              44.8
AD 3 Temporal Ctx              5.3
AD 4 Temporal Ctx              36.9
AD 5 Inf Temporal Ctx          17.8
AD 5 SupTemporal Ctx           31.4
AD 6 Inf Temporal Ctx          53.2
AD 6 Sup Temporal Ctx          44.8
Control 1 Temporal Ctx         13.7
Control 2 Temporal Ctx         17.0
Control 3 Temporal Ctx         19.5
Control 4 Temporal Ctx         19.6
Control (Path) 1 Temporal Ctx  24.1
Control (Path) 2 Temporal Ctx  21.8
Control (Path) 3 Temporal Ctx  10.0
Control (Path) 4 Temporal Ctx  17.7
AD 1 Occipital Ctx             6.0
AD 2 Occipital Ctx (Missing)   0.0
AD 3 Occipital Ctx             1.7
AD 4 Occipital Ctx             16.2
AD 5 Occipital Ctx             5.6
AD 6 Occipital Ctx             23.5
Control 1 Occipital Ctx        1.4
Control 2 Occipital Ctx        16.2
Control 3 Occipital Ctx        10.3
Control 4 Occipital Ctx        10.7
Control (Path) 1 Occipital Ctx 29.7
Control (Path) 2 Occipital Ctx 4.4
Control (Path) 3 Occipital Ctx 1.2
Control (Path) 4 Occipital Ctx 8.7
Control 1 Parietal Ctx         10.8
Control 2 Parietal Ctx         16.3
Control 3 Parietal Ctx         8.4
Control (Path) 1 Parietal Ctx  28.3
Control (Path) 2 Parietal Ctx  11.3
Control (Path) 3 Parietal Ctx  3.1
Control (Path) 4 Parietal Ctx  27.0

[0933]

TABLE ACC
Panel 4D
                                 Rel. Exp. (%)
                                 Ag3441, Run
Tissue Name                      166397101
Secondary Th1 act                0.0
Secondary Th2 act                0.5
Secondary Tr1 act                0.0
Secondary Th1 rest               0.0
Secondary Th2 rest               0.0
Secondary Tr1 rest               0.0
Primary Th1 act                  0.0
Primary Th2 act                  0.0
Primary Tr1 act                  0.0
Primary Th1 rest                 0.0
Primary Th2 rest                 0.0
Primary Tr1 rest                 0.0
CD45RA CD4 lymphocyte act        0.0
CD45RO CD4 lymphocyte act        0.0
CD8 lymphocyte act               0.0
Secondary CD8 lymphocyte rest    0.0
Secondary CD8 lymphocyte act     0.0
CD4 lymphocyte none              0.1
2ry Th1/Th2/Tr1_anti-CD95 CH11   0.0
LAK cells rest                   0.2
LAK cells IL-2                   0.0
LAK cells IL-2 + IL-12           0.0
LAK cells IL-2 + IFN gamma       0.0
LAK cells IL-2 + IL-18           0.0
LAK cells PMA/ionomycin          0.0
NK Cells IL-2 rest               0.0
Two Way MLR 3 day                0.0
Two Way MLR 5 day                0.0
Two Way MLR 7 day                0.0
PBMC rest                        0.0
PBMC PWM                         0.0
PBMC PHA-L                       0.0
Ramos (B cell) none              0.0
Ramos (B cell) ionomycin         0.0
B lymphocytes PWM                0.0
B lymphocytes CD40L and IL-4     0.3
EOL-1 dbcAMP                     0.0
EOL-1 dbcAMP PMA/ionomycin       0.0
Dendritic cells none             3.9
Dendritic cells LPS              0.7
Dendritic cells anti-CD40        5.0
Monocytes rest                   0.1
Monocytes LPS                    0.2
Macrophages rest                 0.8
Macrophages LPS                  0.4
HUVEC none                       0.0
HUVEC starved                    0.0
HUVEC IL-1beta                   0.0
HUVEC IFN gamma                  0.0
HUVEC TNF alpha + IFN gamma      0.0
HUVEC TNF alpha + IL4            0.0
HUVEC IL-11                      0.0
Lung Microvascular EC none       0.0
Lung Microvascular EC TNFalpha + IL-1beta 0.0
Microvascular Dermal EC none     0.0
Microsvasular Dermal EC TNFalpha + IL-1beta 0.0
Bronchial epithelium TNFalpha + IL1beta 0.0
Small airway epithelium none     0.0
Small airway epithelium TNFalpha + IL-1beta 0.0
Coronery artery SMC rest         0.0
Coronery artery SMC TNFalpha + IL-1beta 0.0
Astrocytes rest                  0.0
Astrocytes TNFalpha + IL-1beta   0.0
KU-812 (Basophil) rest           0.0
KU-812 (Basophil) PMA/ionomycin  0.0
CCD1106 (Keratinocytes) none     0.0
CCD1106 (Keratinocytes) TNFalpha + IL-1beta 0.0
Liver cirrhosis                  25.7
Lupus kidney                     13.3
NCI-H292 none                    0.0
NCI-H292 IL-4                    0.0
NCI-H292 IL-9                    0.0
NCI-H292 IL-13                   0.1
NCI-H292 IFN gamma               0.0
HPAEC none                       0.0
HPAEC TNF alpha + IL-1 beta      0.0
Lung fibroblast none             0.1
Lung fibroblast TNF alpha + IL-1 beta 0.0
Lung fibroblast IL-4             0.0
Lung fibroblast IL-9             0.0
Lung fibroblast IL-13            0.0
Lung fibroblast IFN gamma        0.0
Dermal fibroblast CCD1070 rest   0.0
Dermal fibroblast CCD1070 TNF alpha 0.0
Dermal fibroblast CCD1070 IL-1 beta 0.0
Dermal fibroblast IFN gamma      0.0
Dermal fibroblast IL-4           0.0
IBD Colitis 2                    0.2
IBD Crohn's                      0.8
Colon                            6.7
Lung                             1.1
Thymus                           100.0
Kidney                           0.9

[0934]

TABLE ACD
general oncology screening panel_v_2.4
                               Rel. Exp. (%)
                               Ag3441, Run
Tissue Name                    267143302
Colon cancer 1                 0.4
Colon cancer NAT 1             0.7
Colon cancer 2                 0.0
Colon cancer NAT 2             0.7
Colon cancer 3                 0.0
Colon cancer NAT 3             3.1
Colon malignant cancer 4       4.1
Colon normal adjacent tissue 4 0.7
Lung cancer 1                  0.8
Lung NAT 1                     1.1
Lung cancer 2                  1.2
Lung NAT 2                     0.8
Squamous cell carcinoma 3      3.0
Lung NAT 3                     0.8
metastatic melanoma 1          4.2
Melanoma 2                     0.3
Melanoma 3                     0.9
metastatic melanoma 4          4.8
metastatic melanoma 5          2.4
Bladder cancer 1               0.4
Bladder cancer NAT 1           0.0
Bladder cancer 2               0.2
Bladder cancer NAT 2           0.0
Bladder cancer NAT 3           0.0
Bladder cancer NAT 4           0.4
Prostate adenocarcinoma 1      15.4
Prostate adenocarcinoma 2      0.8
Prostate adenocarcinoma 3      2.2
Prostate adenocarcinoma 4      1.0
Prostate cancer NAT 5          0.7
Prostate adenocarcinoma 6      0.7
Prostate adenocarcinoma 7      1.1
Prostate adenocarcinoma 8      0.0
Prostate adenocarcinoma 9      6.6
Prostate cancer NAT 10         0.0
Kidney cancer 1                16.7
Kidney NAT 1                   3.8
Kidney cancer 2                100.0
Kidney NAT 2                   13.0
Kidney cancer 3                70.2
Kidney NAT 3                   9.3
Kidney cancer 4                52.9
Kidney NAT 4                   21.9

[0935] CNS_neurodegeneration_v1.0 Summary: Ag3441 This panel confirms the expression of this gene at low levels in the brain in an independent group of individuals. This gene is found to be slightly upregulated in the temporal cortex of Alzheimer's disease patients. Therefore, therapeutic modulation of the expression or function of this gene may decrease neuronal death and be of use in the treatment of this disease.

[0936] Panel 4D Summary: Ag3441 Highest expression of this gene is detected in thymus. This gene could therefore play an important role in T cell development. Small molecule therapeutics, or antibody therapeutics designed against the protein encoded for by this gene could be utilized to modulate immune function (T cell development) and be important for organ transplant, AIDS treatment or post chemotherapy immune reconstitiution.

[0937] In addition, moderate to low levels of expression of this gene is also detected in dendritic cells, colon, lung, normal and lupus kidney and liver cirrhosis. Therefore, therapeutic modulation of this gene may be useful in the treatment of autoimmune and inflammatory diseases that affect colon, lung and kidney, such as psoriasis, allergy, asthma, inflammatory bowel disease, rheumatoid arthritis and osteoarthritis general oncology screening panel_V—2.4 Summary: Ag3441 Highest expression of this gene is detected in kidney cancer 2 (CT=28.8). Moderate to low levels of expression of this gene is also seen in metastatic melanoma, prostate and kidney cancers. Interestingly, expression of this gene is higher in kidney cancer samples than in the adjacent normal samples. Thus, expression of this gene may be used as marker to detect kidney cancer. In addition, therapeutic modulation of this gene may be useful in the treatment of kidney cancers.

[0938] AD. CG59482-02: Trypsin I Precursor

TABLE ADA
Probe Name Ag7118
			Start
Primers	Sequences	Length	Position	SEQ ID No
Forward	5′-gctaagtgtgaagcctcctacc-	22	194	317
	3′
Probe	TET-5′-agcccacacagaacatgtt	29	223	318
	gctggtaatc-3′-TAMRA
Reverse	5′-gaatccttgcctccctca-3′	18	256	319

[0939]

TABLE ADB
CNS_neurodegeneration_v1.0
                               Rel. Exp. (%)
                               Ag7118, Run
Tissue Name                    296423773
AD 1 Hippo                     13.1
AD 2 Hippo                     13.3
AD 3 Hippo                     4.8
AD 4 Hippo                     5.0
AD 5 hippo                     51.4
AD 6 Hippo                     32.5
Control 2 Hippo                34.2
Control 4 Hippo                5.8
Control (Path) 3 Hippo         2.4
AD 1 Temporal Ctx              10.2
AD 2 Temporal Ctx              37.9
AD 3 Temporal Ctx              6.5
AD 4 Temporal Ctx              17.1
AD 5 Inf Temporal Ctx          77.9
AD 5 Sup Temporal Ctx          22.1
AD 6 Inf Temporal Ctx          30.1
AD 6 Sup Temporal Ctx          51.8
Control 1 Temporal Ctx         4.5
Control 2 Temporal Ctx         59.9
Control 3 Temporal Ctx         17.1
Control 4 Temporal Ctx         9.0
Control (Path) 1 Temporal Ctx  65.1
Control (Path) 2 Temporal Ctx  40.9
Control (Path) 3 Temporal Ctx  8.1
Control (Path) 4 Temporal Ctx  24.5
AD 1 Occipital Ctx             11.3
AD 2 Occipital Ctx (Missing)   0.0
AD 3 Occipital Ctx             6.7
AD 4 Occipital Ctx             12.9
AD 5 Occipital Ctx             17.6
AD 6 Occipital Ctx             39.8
Control 1 Occipital Ctx        2.7
Control 2 Occipital Ctx        100.0
Control 3 Occipital Ctx        12.7
Control 4 Occipital Ctx        2.3
Control (Path) 1 Occipital Ctx 73.7
Control (Path) 2 Occipital Ctx 7.0
Control (Path) 3 Occipital Ctx 2.9
Control (Path) 4 Occipital Ctx 15.5
Control 1 Parietal Ctx         7.4
Control 2 Parietal Ctx         29.3
Control 3 Parietal Ctx         23.5
Control (Path) 1 Parietal Ctx  74.2
Control (Path) 2 Parietal Ctx  15.1
Control (Path) 3 Parietal Ctx  10.6
Control (Path) 4 Parietal Ctx  27.5

[0940]

TABLE ADC
General_screening_panel_v1.6
                                 Rel. Exp. (%)
                                 Ag7118, Run
Tissue Name                      296433067
Adipose                          0.0
Melanoma* Hs688(A).T             0.0
Melanoma* Hs688(B).T             0.0
Melanoma* M14                    0.0
Melanoma* LOXIMVI                0.0
Melanoma* SK-MEL-5               0.0
Squamous cell carcinoma SCC-4    0.0
Testis Pool                      0.0
Prostate ca.* (bone met) PC-3    0.0
Prostate Pool                    0.0
Placenta                         0.0
Uterus Pool                      0.0
Ovarian ca. OVCAR-3              0.2
Ovarian ca. SK-OV-3              0.0
Ovarian ca. OVCAR-4              0.0
Ovarian ca. OVCAR-5              0.0
Ovarian ca. IGROV-1              0.0
Ovarian ca. OVCAR-8              0.0
Ovary                            0.0
Breast ca. MCF-7                 0.0
Breast ca. MDA-MB-231            0.0
Breast ca. BT 549                0.0
Breast ca. T47D                  0.0
Breast ca. MDA-N                 0.0
Breast Pool                      0.0
Trachea                          0.0
Lung                             0.0
Fetal Lung                       0.0
Lung ca. NCI-N417                0.0
Lung ca. LX-1                    0.0
Lung ca. NCI-H146                0.0
Lung ca. SHP-77                  0.0
Lung ca. A549                    0.0
Lung ca. NCI-H526                0.0
Lung ca. NCI-H23                 0.0
Lung ca. NCI-H460                0.0
Lung ca. HOP-62                  0.0
Lung ca. NCI-H522                0.0
Liver                            0.0
Fetal Liver                      0.1
Liver ca. HepG2                  0.0
Kidney Pool                      0.0
Fetal Kidney                     0.0
Renal ca. 786-0                  0.0
Renal ca. A498                   0.0
Renal ca. ACHN                   0.0
Renal ca. UO-31                  0.0
Renal ca. TK-10                  0.0
Bladder                          18.4
Gastric ca. (liver met.) NCI-N87 0.0
Gastric ca. KATO III             0.0
Colon ca. SW-948                 0.0
Colon ca. SW480                  0.0
Colon ca.* (SW480 met) SW620     0.0
Colon ca. HT29                   0.0
Colon ca. HCT-116                0.0
Colon ca. CaCo-2                 0.0
Colon cancer tissue              0.0
Colon ca. SW1116                 0.0
Colon ca. Colo-205               0.0
Colon ca. SW-48                  0.0
Colon Pool                       0.0
Small Intestine Pool             0.0
Stomach Pool                     0.0
Bone Marrow Pool                 0.0
Fetal Heart                      0.0
Heart Pool                       0.0
Lymph Node Pool                  0.0
Fetal Skeletal Muscle            0.0
Skeletal Muscle Pool             0.0
Spleen Pool                      0.0
Thymus Pool                      0.0
CNS cancer (glio/astro) U87-MG   0.0
CNS cancer (glio/astro) U-118-MG 0.0
CNS cancer (neuro; met) SK-N-AS  0.0
CNS cancer (astro) SF-539        0.0
CNS cancer (astro) SNB-75        0.0
CNS cancer (glio) SNB-19         0.0
CNS cancer (glio) SF-295         0.0
Brain (Amygdala) Pool            0.0
Brain (cerebellum)               0.0
Brain (fetal)                    0.0
Brain (Hippocampus) Pool         0.0
Cerebral Cortex Pool             0.0
Brain (Substantia nigra) Pool    0.0
Brain (Thalamus) Pool            0.0
Brain (whole)                    0.0
Spinal Cord Pool                 0.0
Adrenal Gland                    0.0
Pituitary gland Pool             0.0
Salivary Gland                   0.0
Thyroid (female)                 0.0
Pancreatic ca. CAPAN2            0.0
Pancreas Pool                    100.0

[0941]

TABLE ADD
Panel 4.1D
                                 Rel. Exp. (%)
                                 Ag7118, Run
Tissue Name                      296417626
Secondary Th1 act                0.0
Secondary Th2 act                1.3
Secondary Tr1 act                0.0
Secondary Th1 rest               4.3
Secondary Th2 rest               13.6
Secondary Tr1 rest               4.3
Primary Th1 act                  0.0
Primary Th2 act                  2.2
Primary Tr1 act                  0.8
Primary Th1 rest                 1.2
Primary Th2 rest                 0.0
Primary Tr1 rest                 0.8
CD45RA CD4 lymphocyte act        12.4
CD45RO CD4 lymphocyte act        11.7
CD8 lymphocyte act               2.6
Secondary CD8 lymphocyte rest    0.0
Secondary CD8 lymphocyte act     4.1
CD4 lymphocyte none              2.3
2ry Th1/Th2/Tr1_anti-CD95 CH11   0.0
LAK cells rest                   0.0
LAK cells IL-2                   15.6
LAK cells IL-2 + IL-12           0.0
LAK cells IL-2 + IFN gamma       1.5
LAK cells IL-2 + IL-18           1.6
LAK cells PMA/ionomycin          8.7
NK Cells IL-2 rest               82.9
Two Way MLR 3 day                32.3
Two Way MLR 5 day                4.5
Two Way MLR 7 day                2.9
PBMC rest                        2.5
PBMC PWM                         0.9
PBMC PHA-L                       0.0
Ramos (B cell) none              0.0
Ramos (B cell) ionomycin         0.0
B lymphocytes PWM                0.0
B lymphocytes CD40L and IL-4     10.7
EOL-1 dbcAMP                     0.0
EOL-1 dbcAMP PMA/ionomycin       0.0
Dendritic cells none             0.0
Dendritic cells LPS              0.0
Dendritic cells anti-CD40        0.0
Monocytes rest                   3.8
Monocytes LPS                    1.3
Macrophages rest                 0.0
Macrophages LPS                  1.2
HUVEC none                       31.9
HUVEC starved                    36.1
HUVEC IL-1beta                   38.4
HUVEC IFN gamma                  10.6
HUVEC TNF alpha + IFN gamma      10.8
HUVEC TNF alpha + IL4            16.4
HUVEC IL-11                      13.6
Lung Microvascular EC none       21.8
Lung Microvascular EC TNFalpha + IL-1beta 6.0
Microvascular Dermal EC none     1.8
Microsvasular Dermal EC TNFalpha + IL-1beta 0.6
Bronchial epithelium TNFalpha + IL1beta 17.4
Small airway epithelium none     3.0
Small airway epithelium TNFalpha + IL-1beta 11.6
Coronery artery SMC rest         15.2
Coronery artery SMC TNFalpha + IL-1beta 16.7
Astrocytes rest                  0.0
Astrocytes TNFalpha + IL-1beta   0.0
KU-812 (Basophil) rest           0.0
KU-812 (Basophil) PMA/ionomycin  0.0
CCD1106 (Keratinocytes) none     100.0
CCD1106 (Keratinocytes) TNFalpha + IL-1beta 16.4
Liver cirrhosis                  8.4
NCI-H292 none                    0.0
NCI-H292 IL-4                    0.0
NCI-H292 IL-9                    0.0
NCI-H292 IL-13                   0.0
NCI-H292 IFN gamma               1.3
HPAEC none                       15.5
HPAEC TNF alpha + IL-1 beta      62.0
Lung fibroblast none             2.4
Lung fibroblast TNF alpha + IL-1 beta 2.2
Lung fibroblast IL-4             3.7
Lung fibroblast IL-9             3.7
Lung fibroblast IL-13            0.0
Lung fibroblast IFN gamma        6.9
Dermal fibroblast CCD1070 rest   47.0
Dermal fibroblast CCD1070 TNF alpha 42.6
Dermal fibroblast CCD1070 IL-1 beta 16.0
Dermal fibroblast IFN gamma      1.1
Dermal fibroblast IL-4           4.4
Dermal Fibroblasts rest          6.3
Neutrophils TNFa + LPS           0.0
Neutrophils rest                 1.6
Colon                            29.3
Lung                             0.0
Thymus                           13.6
Kidney                           7.5

[0942] CNS_neurodegeneration_v1.0 Summary: Ag7l18 This panel confirms the expression of this gene at low levels in the brain in an independent group of individuals. This gene appears to be slightly down-regulated in the temporal cortex of Alzheimer's disease patients. Therefore, up-regulation of this gene or its protein product, or treatment with specific agonists for this receptor may be of use in reversing the dementia, memory loss, and neuronal death associated with this disease.

[0943] General_screening_panel_v1.6 Summary: Ag7118 Highest expression of this gene, a putative trypsin, is seen in the pancreas (CT=17). Thus, expression of this gene could be used to differentiate between this gene and other genes on this panel and as a marker of this organ. In addition, therapeutic modulation of the trypsin encoded by this gene may be useful in the treatment of pancrease related diseases including pancreatitis.

[0944] Panel 4.1D Summary: Ag7118 Highest expression is seen in untreated keratinocytes (CT=32.6). Therefore, modulation of the expression or activity of the protein encoded by this transcript through the application of small molecule therapeutics may be useful in the treatment of psoriasis and wound healing.

[0945] In addition, low to moderate levels of this gene is also detected in cytokine treated dermal fibroblasts, HPAEC, resting and activated HUVEC cells, IL2-treated resting NK cells, and 2 way MLR. Therefore, therapeutic modulation of the trypsin encoded by this gene may be useful in the treatment of autoimmune and inflammatory diseases that involve endothelial cells, such as lupus erythematosus, asthma, emphysema, Crohn's disease, ulcerative colitis, rheumatoid arthritis, osteoarthritis, and psoriasis.

[0946] AE. CG89709-01 and CG89709-02 and CG89709-03 and CG89709-04: Protein Kinase-Like Gene

[0947] Expression of gene CG89709-01 and variants CG89709-02, CG89709-03, and CG89709-04 was assessed using the primer-probe set Ag5763, described in Table AEA. Results of the RTQ-PCR runs are shown in Tables AEB, AEC and AED.

TABLE AEA
Probe Name Ag5763
			Start
Primers	Sequences	Length	Position	SEQ ID No
Forward	5′-atggcagccagcattaaa-3′	19	3047	320
Probe	TET-5′-tccatctacgtgtattaca	29	3078	321
	gacattctgc-3′-TAMRA
Reverse	5′-agacttcggggtgcttgtag-3′	20	3111	322

[0948]

TABLE AEB
CNS_neurodegeneration_v1.0
                               Rel. Exp. (%)
                               Ag5763, Run
Tissue Name                    249286625
AD 1 Hippo                     17.0
AD 2 Hippo                     35.8
AD 3 Hippo                     6.2
AD 4 Hippo                     8.9
AD 5 hippo                     71.2
AD 6 Hippo                     53.2
Control 2 Hippo                36.3
Control 4 Hippo                16.6
Control (Path) 3 Hippo         8.2
AD 1 Temporal Ctx              28.3
AD 2 Temporal Ctx              41.8
AD 3 Temporal Ctx              8.8
AD 4 Temporal Ctx              43.5
AD 5 Inf Temporal Ctx          84.7
AD 5 Sup Temporal Ctx          45.1
AD 6 Inf Temporal Ctx          58.6
AD 6 Sup Temporal Ctx          58.6
Control 1 Temporal Ctx         6.6
Control 2 Temporal Ctx         40.6
Control 3 Temporal Ctx         18.4
Control 4 Temporal Ctx         10.9
Control (Path) 1 Temporal Ctx  68.8
Control (Path) 2 Temporal Ctx  36.9
Control (Path) 3 Temporal Ctx  5.1
Control (Path) 4 Temporal Ctx  37.1
AD 1 Occipital Ctx             20.0
AD 2 Occipital Ctx (Missing)   0.0
AD 3 Occipital Ctx             7.9
AD 4 Occipital Ctx             29.7
AD 5 Occipital Ctx             20.6
AD 6 Occipital Ctx             48.6
Control 1 Occipital Ctx        4.4
Control 2 Occipital Ctx        75.3
Control 3 Occipital Ctx        21.3
Control 4 Occipital Ctx        9.5
Control (Path) 1 Occipital Ctx 100.0
Control (Path) 2 Occipital Ctx 14.4
Control (Path) 3 Occipital Ctx 4.1
Control (Path) 4 Occipital Ctx 17.8
Control 1 Parietal Ctx         9.1
Control 2 Parietal Ctx         49.3
Control 3 Parietal Ctx         18.7
Control (Path) 1 Parietal Ctx  85.9
Control (Path) 2 Parietal Ctx  14.3
Control (Path) 3 Parietal Ctx  3.6
Control (Path) 4 Parietal Ctx  54.0

[0949]

TABLE AEC
General_screening_panel_v1.5
                                 Rel. Exp. (%)
                                 Ag5763, Run
Tissue Name                      246263911
Adipose                          7.2
Melanoma* Hs688(A).T             11.3
Melanoma* Hs688(B).T             12.5
Melanoma* M14                    8.1
Melanoma* LOXIMVI                8.5
Melanoma* SK-MEL-5               10.9
Squamous cell carcinoma SCC-4    6.9
Testis Pool                      13.2
Prostate ca.* (bone met) PC-3    6.6
Prostate Pool                    4.8
Placenta                         15.9
Uterus Pool                      9.3
Ovarian ca. OVCAR-3              8.9
Ovarian ca. SK-OV-3              14.3
Ovarian ca. OVCAR-4              10.3
Ovarian ca. OVCAR-5              18.4
Ovarian ca. IGROV-1              9.5
Ovarian ca. OVCAR-8              5.2
Ovary                            7.7
Breast ca. MCF-7                 3.6
Breast ca. MDA-MB-231            17.0
Breast ca. BT 549                15.9
Breast ca. T47D                  1.1
Breast ca. MDA-N                 4.0
Breast Pool                      14.5
Trachea                          9.2
Lung                             3.8
Fetal Lung                       18.6
Lung ca. NCI-N417                3.6
Lung ca. LX-1                    5.5
Lung ca. NCI-H146                5.7
Lung ca. SHP-77                  10.4
Lung ca. A549                    9.0
Lung ca. NCI-H526                7.4
Lung ca. NCI-H23                 19.2
Lung ca. NCI-H460                7.9
Lung ca. HOP-62                  5.3
Lung ca. NCI-H522                8.0
Liver                            2.6
Fetal Liver                      14.3
Liver ca. HepG2                  9.8
Kidney Pool                      19.3
Fetal Kidney                     8.9
Renal ca. 786-0                  7.7
Renal ca. A498                   0.9
Renal ca. ACHN                   7.6
Renal ca. UO-31                  7.3
Renal ca. TK-10                  9.1
Bladder                          9.8
Gastric ca. (liver met.) NCI-N87 15.5
Gastric ca. KATO III             46.3
Colon ca. SW-948                 3.3
Colon ca. SW480                  13.0
Colon ca.* (SW480 met) SW620     7.9
Colon ca. HT29                   3.2
Colon ca. HCT-116                9.7
Colon ca. CaCo-2                 28.9
Colon cancer tissue              4.8
Colon ca. SW1116                 1.5
Colon ca. Colo-205               1.9
Colon ca. SW-48                  2.0
Colon Pool                       13.3
Small Intestine Pool             15.8
Stomach Pool                     6.8
Bone Marrow Pool                 5.5
Fetal Heart                      6.6
Heart Pool                       6.0
Lymph Node Pool                  15.6
Fetal Skeletal Muscle            5.7
Skeletal Muscle Pool             18.8
Spleen Pool                      7.8
Thymus Pool                      11.8
CNS cancer (glio/astro) U87-MG   5.1
CNS cancer (glio/astro) U-118-MG 20.7
CNS cancer (neuro; met) SK-N-AS  3.7
CNS cancer (astro) SF-539        6.7
CNS cancer (astro) SNB-75        18.9
CNS cancer (glio) SNB-19         7.9
CNS cancer (glio) SF-295         16.0
Brain (Amygdala) Pool            22.5
Brain (cerebellum)               100.0
Brain (fetal)                    20.6
Brain (Hippocampus) Pool         26.1
Cerebral Cortex Pool             25.5
Brain (Substantia nigra) Pool    21.3
Brain (Thalamus) Pool            36.9
Brain (whole)                    20.7
Spinal Cord Pool                 16.6
Adrenal Gland                    10.2
Pituitary gland Pool             5.3
Salivary Gland                   4.1
Thyroid (female)                 5.4
Pancreatic ca. CAPAN2            12.8
Pancreas Pool                    20.2

[0950]

TABLE AED
Panel 5 Islet
                                 Rel. Exp. (%)
                                 Ag5763, Run
Tissue Name                      243564954
97457_Patient-02go_adipose       23.3
97476_Patient-07sk_skeletal muscle 27.4
97477_Patient-07ut_uterus        17.2
97478_Patient-07pl_placenta      43.8
99167_Bayer Patient 1            64.6
97482_Patient-08ut_uterus        11.3
97483_Patient-08pl_placenta      56.6
97486_Patient-09sk_skeletal muscle 14.8
97487_Patient-09ut_uterus        36.9
97488_Patient-09pl_placenta      21.0
97492_Patient-10ut_uterus        31.6
97493_Patient-10pl_placenta      100.0
97495_Patient-11go_adipose       24.8
97496_Patient-11sk_skeletal muscle 28.5
97497_Patient-11ut_uterus        43.2
97498_Patient-11pl_placenta      34.4
97500_Patient-12go_adipose       37.6
97501_Patient-12sk_skeletal muscle 57.8
97502_Patient-12ut_uterus        34.4
97503_Patient-12pl_placenta      40.1
94721_Donor 2 U - A_Mesenchymal Stem Cells 17.9
94722_Donor 2 U - B_Mesenchymal Stem Cells 21.6
94723_Donor 2 U - C_Mesenchymal Stem Cells 27.5
94709_Donor 2 AM - A_adipose     19.6
94710_Donor 2 AM - B_adipose     15.4
94711_Donor 2 AM - C_adipose     9.1
94712_Donor 2 AD - A_adipose     37.4
94713_Donor 2 AD - B_adipose     40.9
94714_Donor 2 AD - C_adipose     39.8
94742_Donor 3 U - A_Mesenchymal Stem Cells 11.7
94743_Donor 3 U - B_Mesenchymal Stem Cells 33.0
94730_Donor 3 AM - A_adipose     42.9
94731_Donor 3 AM - B_adipose     11.5
94732_Donor 3 AM - C_adipose     25.5
94733_Donor 3 AD - A_adipose     73.7
94734_Donor 3 AD - B_adipose     20.9
94735_Donor 3 AD - C_adipose     46.3
77138_Liver_HepG2untreated       40.9
73556_Heart_Cardiac stromal cells (primary) 7.9
81735_Small Intestine            40.6
72409_Kidney_Proximal Convoluted Tubule 11.8
82685_Small intestine_Duodenum   15.7
90650_Adrenal_Adrenocortical adenoma 8.1
72410_Kidney_HRCE                40.9
72411_Kidney_HRE                 18.4
73139_Uterus_Uterine smooth muscle cells 11.1

[0951] CNS_neurodegeneration_v1.0 Summary: Ag5763 This panel confirms the expression of this gene at significant levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.5 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.

[0952] General_screening_panel_v1.5 Summary: Ag5763 Highest expression of this gene is detected in brain (cerebellum) (CT=26.4). High levels of expression of this gene is also seen 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.

[0953] Moderate levels of expression of this gene is also seen in cluster of cancer cell lines derived from pancreatic, gastric, colon, lung, liver, 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, liver, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers.

[0954] 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.

[0955] This gene codes for a novel protein kinase. In PathCalling screening at Curagen, this gene was identified as an interactor of estrogen-related nuclear receptor beta 2 (ERRB2). ERRB2, in turn, interacts with FOXO1A (FKHR), an important transcriptional factor in metabolism. This result suggests that the novel protein kinase may control the phosphorylation state of ERRB2 and FKHR and therefore, their activity. Therefore, inhibition of this gene would impair excessive activities of ERRB2 and FHKR, known to be associated with diabetic condition. Thus, an antagonist of the protein kinase encoded by this gene would be beneficial for the treatment of diabetes.

[0956] Panel 5 Islet Summary: Ag5763 Highest expression of this gene is detected in placenta (CT=29.9). In addition, consistent with panel 1.5 this gene is widely expressed in metabolic tissues. Please see panel 1.5 for further discussion on the utility of this gene.

[0957] AF. CG90879-01: Protein Kinase D2-Like Gene

[0958] Expression of gene CG90879-01 was assessed using the primer-probe sets Ag805 and Ag3770, described in Tables AFA and AFB. Results of the RTQ-PCR runs are shown in Tables AFC, AFD, AFE, AFF and AFG.

TABLE AFA
Probe Name Ag805
			Start
Primers	Sequences	Length	Position	SEQ ID No
Forward	5′-ccttcgaggacttccagatc-	20	428	323
	3′
Probe	TET-5′-acgccctcacggtgcac	23	455	324
	tcctat-3′-TAMRA
Reverse	5′-actaggccgaagagcatctc-	20	508	325
	3′

[0959]

TABLE AFB
Probe Name Ag3770
			Start
Primers	Sequences	Length	Position	SEQ ID No
Forward	5′-atccaagagaatgtggacattg-	22	1681	326
	3′
Probe	TET-5′-accagatcttccctgacg	26	1712	327
	aagtgctg-3′-TAMRA
Reverse	5′-ctccatagaccactccaaactg-	22	1747	328
	3′

[0960]

TABLE AFC
CNS_neurodegeneration_v1.0
	Rel. Exp. (%)	Rel. Exp. (%)
	Ag3770, Run	Ag805, Run
Tissue Name	211175147	224758713
AD 1 Hippo	41.5	27.4
AD 2 Hippo	32.8	17.0
AD 3 Hippo	29.9	14.1
AD 4 Hippo	24.5	6.8
AD 5 Hippo	54.0	59.5
AD 6 Hippo	100.0	100.0
Control 2 Hippo	27.9	10.9
Control 4 Hippo	57.8	36.1
Control (Path) 3 Hippo	23.2	4.8
AD 1 Temporal Ctx	47.0	24.7
AD 2 Temporal Ctx	22.7	9.1
AD 3 Temporal Ctx	25.5	9.2
AD 4 Temporal Ctx	21.2	4.4
AD 5 Inf Temporal Ctx	94.0	57.8
AD 5 Sup Temporal Ctx	60.7	52.9
AD 6 Inf Temporal Ctx	95.3	67.4
AD 6 Sup Temporal Ctx	96.6	54.0
Control 1 Temporal Ctx	20.2	4.3
Control 2 Temporal Ctx	40.3	22.1
Control 3 Temporal Ctx	28.5	8.6
Control 3 Temporal Ctx	18.3	14.7
Control (Path) 1	61.1	20.3
Temporal Ctx
Control (Path) 2	36.3	17.4
Temporal Ctx
Control (Path) 3	23.3	17.7
Temporal Ctx
Control (Path) 4	26.1	13.8
Temporal Ctx
AD 1 Occipital Ctx	34.2	18.8
AD 2 Occipital Ctx (Missing)	0.0	0.0
AD 3 Occipital Ctx	33.2	19.2
AD 4 Occipital Ctx	23.2	8.6
AD 5 Occipital Ctx	44.1	29.9
AD 6 Occipital Ctx	62.9	13.8
Control 1 Occipital Ctx	25.3	8.3
Control 2 Occipital Ctx	32.1	25.7
Control 3 Occipital Ctx	22.7	12.2
Control 4 Occipital Ctx	22.7	14.8
Control (Path) 1	80.1	54.7
Occipital Ctx
Control (Path) 2	17.8	15.0
Occipital Ctx
Control (Path) 3	18.2	6.0
Occipital Ctx
Control (Path) 4	22.2	15.4
Occipital Ctx
Control 1 Parietal Ctx	33.7	9.1
Control 2 Parietal Ctx	53.2	36.3
Control 3 Parietal Ctx	10.9	12.1
Control (Path) 1 Parietal Ctx	54.3	31.9
Control (Path) 2 Parietal Ctx	24.3	11.3
Control (Path) 3	22.5	6.4
Parietal Ctx
Control (Path) 4	37.4	22.2
Parietal Ctx

[0961]

TABLE AFD
General screening_panel_v1.4
                                 Rel. Exp. (%)
                                 Ag3770, Run
Tissue Name                      218982439
Adipose                          4.5
Melanoma* Hs688(A).T             7.9
Melanoma* Hs688(B).T             8.8
Melanoma* M14                    15.7
Melanoma* LOXIMVI                19.1
Melanoma* SK-MEL-5               7.8
Squamous cell carcinoma SCC-4    16.7
Testis Pool                      3.3
Prostate ca.* (bone met) PC-3    13.6
Prostate Pool                    7.5
Placenta                         12.7
Uterus Pool                      3.6
Ovarian ca. OVCAR-3              16.2
Ovarian ca. SK-OV-3              37.4
Ovarian ca. OVCAR-4              12.7
Ovarian ca. OVCAR-5              30.6
Ovarian ca. IGROV-1              22.1
Ovarian ca. OVCAR-8              12.1
Ovary                            6.0
Breast ca. MCF-7                 22.1
Breast ca. MDA-MB-231            20.6
Breast ca. BT 549                24.1
Breast ca. T47D                  58.6
Breast ca. MDA-N                 4.3
Breast Pool                      8.1
Trachea                          9.7
Lung                             2.2
Fetal Lung                       25.7
Lung ca. NCI-N417                2.2
Lung ca. LX-1                    16.3
Lung ca. NCI-H146                4.5
Lung ca. SHP-77                  10.3
Lung ca. A549                    19.2
Lung ca. NCI-H526                4.1
Lung ca. NCI-H23                 8.5
Lung ca. NCI-H460                4.2
Lung ca. HOP-62                  7.9
Lung ca. NCI-H522                13.3
Liver                            1.1
Fetal Liver                      5.8
Liver ca. HepG2                  6.4
Kidney Pool                      13.2
Fetal Kidney                     7.8
Renal ca. 786-0                  11.9
Renal ca. A498                   12.3
Renal ca. ACHN                   13.8
Renal ca. UO-31                  18.7
Renal ca. TK-10                  15.8
Bladder                          23.0
Gastric ca. (liver met.) NCI-N87 100.0
Gastric ca. KATO III             42.9
Colon ca. SW-948                 13.6
Colon ca. SW480                  33.2
Colon ca.* (SW480 met) SW620     13.1
Colon ca. HT29                   18.6
Colon ca. HCT-116                48.0
Colon ca. CaCo-2                 28.5
Colon cancer tissue              15.5
Colon ca. SW1116                 7.4
Colon ca. Colo-205               7.2
Colon ca. SW-48                  6.9
Colon Pool                       8.7
Small Intestine Pool             9.5
Stomach Pool                     7.2
Bone Marrow Pool                 2.5
Fetal Heart                      5.8
Heart Pool                       3.6
Lymph Node Pool                  8.1
Fetal Skeletal Muscle            3.9
Skeletal Muscle Pool             3.3
Spleen Pool                      12.6
Thymus Pool                      16.2
CNS cancer (glio/astro) U87-MG   16.8
CNS cancer (glio/astro) U-118-MG 23.3
CNS cancer (neuro; met) SK-N-AS  26.2
CNS cancer (astro) SF-539        8.5
CNS cancer (astro) SNB-75        15.9
CNS cancer (glio) SNB-19         20.6
CNS cancer (glio) SF-295         50.7
Brain (Amygdala) Pool            1.9
Brain (cerebellum)               2.8
Brain (fetal)                    4.1
Brain (Hippocampus) Pool         2.3
Cerebral Cortex Pool             1.9
Brain (Substantia nigra) Pool    2.5
Brain (Thalamus) Pool            2.3
Brain (whole)                    2.6
Spinal Cord Pool                 1.7
Adrenal Gland                    4.8
Pituitary gland Pool             3.1
Salivary Gland                   4.4
Thyroid (female)                 7.6
Pancreatic ca. CAPAN2            22.1
Pancreas Pool                    8.0

[0962]

TABLE AFE
Panel 1.3D
                                 Rel. Exp. (%)
                                 Ag805, Run
Tissue Name                      167966906
Liver adenocarcinoma             80.1
Pancreas                         12.5
Pancreatic ca. CAPAN 2           25.7
Adrenal gland                    6.1
Thyroid                          14.9
Salivary gland                   10.2
Pituitary gland                  21.2
Brain (fetal)                    11.7
Brain (whole)                    6.0
Brain (amygdala)                 7.6
Brain (cerebellum)               2.6
Brain (hippocampus)              3.1
Brain (substantia nigra)         6.3
Brain (thalamus)                 3.6
Cerebral Cortex                  8.1
Spinal cord                      7.7
glio/astro U87-MG                19.3
glio/astro U-118-MG              11.2
astrocytoma SW1783               18.4
neuro*; met SK-N-AS              27.4
astrocytoma SF-539               23.5
astrocytoma SNB-75               44.4
glioma SNB-19                    55.9
glioma U251                      33.0
glioma SF-295                    67.8
Heart (fetal)                    41.8
Heart                            11.9
Skeletal muscle (fetal)          38.4
Skeletal muscle                  7.9
Bone marrow                      19.6
Thymus                           97.9
Spleen                           37.4
Lymph node                       55.9
Colorectal                       9.3
Stomach                          13.2
Small intestine                  13.9
Colon ca. SW480                  48.3
Colon ca.* SW620(SW480 met)      42.6
Colon ca. HT29                   33.4
Colon ca. HCT-116                24.1
Colon ca. CaCo-2                 42.9
Colon ca. tissue(ODO3866)        21.8
Colon ca. HCC-2998               46.7
Gastric ca.* (liver met) NCI-N87 82.9
Bladder                          18.2
Trachea                          20.9
Kidney                           19.9
Kidney (fetal)                   100.0
Renal ca. 786-0                  22.5
Renal ca. A498                   30.8
Renal ca. RXF 393                72.2
Renal ca. ACHN                   41.8
Renal ca. UO-31                  26.1
Renal ca. TK-10                  25.0
Liver                            11.3
Liver (fetal)                    9.7
Liver ca. (hepatoblast) HepG2    15.3
Lung                             36.6
Lung (fetal)                     27.9
Lung ca. (small cell) LX-1       27.5
Lung ca. (small cell) NCI-H69    20.3
Lung ca. (s. cell var.) SHP-77   35.6
Lung ca. (large cell) NCI-H460   3.8
Lung ca. (non-sm. cell) A549     47.3
Lung ca. (non-s. cell) NCI-H23   13.4
Lung ca. (non-s. cell) HOP-62    21.0
Lung ca. (non-s. cl) NCI-H522    24.8
Lung ca. (squam.) SW 900         40.3
Lung ca. (squam.) NCI-H596       16.7
Mammary gland                    31.4
Breast ca.* (pl. ef) MCF-7       26.2
Breast ca.* (pl. ef) MDA-MB-231  19.1
Breast ca.* (pl. ef) T47D        34.4
Breast ca. BT-549                13.3
Breast ca. MDA-N                 6.7
Ovary                            33.9
Ovarian ca. OVCAR-3              17.1
Ovarian ca. OVCAR-4              48.6
Ovarian ca. OVCAR-5              75.8
Ovarian ca. OVCAR-8              10.9
Ovarian ca. IGROV-1              11.7
Ovarian ca.* (ascites) SK-OV-3   52.5
Uterus                           20.2
Placenta                         4.6
Prostate                         14.3
Prostate ca.* (bone met)PC-3     14.7
Testis                           6.8
Melanoma Hs688(A).T              7.0
Melanoma* (met) Hs688(B).T       7.3
Melanoma UACC-62                 31.6
Melanoma M14                     8.5
Melanoma LOX IMVI                46.0
Melanoma* (met) SK-MEL-5         7.2
Adipose                          13.6

[0963]

TABLE AFF
Panel 4.1D
	Rel. Exp. (%)	Rel. Exp. (%)
	Ag3770, Run	Ag805, Run
Tissue Name	170069171	169990844
Secondary Th1 act	52.1	33.4
Secondary Th2 act	100.0	73.7
Secondary Tr1 act	67.4	40.9
Secondary Th1 rest	41.8	30.1
Secondary Th2 rest	81.2	58.6
Secondary Tr1 rest	57.0	47.3
Primary Th1 act	41.2	19.8
Primary Th2 act	62.0	35.8
Primary Tr1 act	50.0	41.5
Primary Th1 rest	61.1	40.1
Primary Th2 rest	48.0	30.8
Primary Tr1 rest	62.0	33.9
CD45RA CD4 lymphocyte act	28.3	25.3
CD45RO CD4 lymphocyte act	49.3	36.6
CD8 lymphocyte act	55.1	48.6
Secondary CD8 lymphocyte rest	33.2	37.9
Secondary CD8 lymphocyte act	39.5	40.3
CD4 lymphocyte none	24.0	43.8
2ry Th1/Th2/Tr1_anti-CD95 CH11	57.4	45.4
LAK cells rest	30.6	19.5
LAK cells IL-2	52.1	33.7
LAK cells IL-2 + IL-12	42.9	39.2
LAK cells IL-2 + IFN gamma	50.7	45.7
LAK cells IL-2 + IL-18	61.6	34.4
LAK cells PMA/ionomycin	16.8	7.7
NK Cells IL-2 rest	77.4	67.4
Two Way MLR 3 day	54.0	100.0
Two Way MLR 5 day	36.3	35.4
Two Way MLR 7 day	37.9	33.0
PBMC rest	33.7	23.0
PBMC PWM	41.5	32.8
PBMC PHA-L	36.6	33.4
Ramos (B cell) none	47.0	48.0
Ramos (B cell) ionomycin	42.9	39.8
B lymphocytes PWM	14.6	14.2
B lymphocytes CD40L and IL-4	59.5	34.9
EOL-1 dbcAMP	25.2	17.3
EOL-1 dbcAMP PMA/ionomycin	57.0	54.7
Dendritic cells none	12.2	6.9
Dendritic cells LPS	10.2	10.4
Dendritic cells anti-CD40	9.6	8.4
Monocytes rest	22.7	20.3
Monocytes LPS	28.5	24.7
Macrophages rest	11.3	11.5
Macrophages LPS	31.0	31.6
HUVEC none	29.5	30.6
HUVEC starved	37.9	40.9
HUVEC IL-1beta	51.8	52.1
HUVEC IFN gamma	58.2	39.2
HUVEC TNF alpha + IFN gamma	35.8	48.0
HUVEC TNF alpha + IL4	29.7	39.2
HUVEC IL-11	26.8	24.5
Lung Microvascular EC none	75.3	68.8
Lung Microvascular EC	59.0	74.7
TNFalpha + IL-1beta
Microvascular Dermal EC none	28.9	35.6
Microsvasular Dermal EC	57.4	66.9
TNFalpha + IL-1beta
Bronchial epithelium	29.9	33.9
TNFalpha + IL1beta
Small airway epithelium none	10.1	13.5
Small airway epithelium	36.6	30.1
TNFalpha + IL-1beta
Coronery artery SMC rest	17.0	13.8
Coronery artery SMC	13.0	9.6
TNFalpha + IL-1beta
Astrocytes rest	20.3	15.9
Astrocytes TNFalpha + IL-1beta	24.8	14.5
KU-812 (Basophil) rest	24.5	16.6
KU-812 (Basophil) PMA/ionomycin	23.5	42.9
CCD1106 (Keratinocytes) none	28.7	28.1
CCD1106 (Keratinocytes)	56.3	55.5
TNFalpha + IL-1beta
Liver cirrhosis	7.9	8.4
NCI-H292 none	32.3	27.2
NCI-H292 IL-4	34.9	28.9
NCI-H292 IL-9	53.2	23.0
NCI-H292 IL-13	35.6	35.6
NCI-H292 IFN gamma	46.3	47.6
HPAEC none	34.9	31.9
HPAEC TNF alpha + IL-1 beta	57.8	53.6
Lung fibroblast none	10.7	11.5
Lung fibroblast	18.9	18.0
TNF alpha + IL-1 beta
Lung fibroblast IL-4	7.6	7.9
Lung fibroblast IL-9	14.3	12.2
Lung fibroblast IL-13	10.7	5.0
Lung fibroblast IFN gamma	15.0	16.3
Dermal fibroblast CCD1070 rest	12.5	13.6
Dermal fibroblast CCD1070 TNF alpha	42.9	40.1
Dermal fibroblast CCD1070 IL-1 beta	11.5	11.3
Dermal fibroblast IFN gamma	9.4	8.7
Dermal fibroblast IL-4	16.6	13.3
Dermal Fibroblasts rest	11.4	8.5
Neutrophils TNFa + LPS	8.7	13.7
Neutrophils rest	54.0	81.2
Colon	15.2	12.0
Lung	34.2	20.9
Thymus	56.6	56.3
Kidney	15.8	5.6

[0964]

TABLE AFG
general oncology screening panel_v_2.4
                          Rel. Exp. (%)
                          Ag3770, Run
Tissue Name               267820395
Colon cancer 1            33.9
Colon NAT 1               21.2
Colon cancer 2            26.4
Colon NAT 2               12.2
Colon cancer 3            64.6
Colon NAT 3               27.5
Colon malignant cancer 4  39.8
Colon NAT 4               7.4
Lung cancer 1             39.5
Lung NAT 1                6.7
Lung cancer 2             84.7
Lung NAT 2                7.6
Squamous cell carcinoma 3 64.2
Lung NAT 3                2.2
Metastatic melanoma 1     29.3
Melanoma 2                34.2
Melanoma 3                12.9
Metastatic melanoma 4     66.9
Metastatic melanoma 5     59.9
Bladder cancer 1          2.5
Bladder NAT 1             0.0
Bladder cancer 2          7.7
Bladder NAT 2             0.0
Bladder NAT 3             0.9
Bladder NAT 4             4.1
Prostate adenocarcinoma 1 38.7
Prostate adenocarcinoma 2 6.9
Prostate adenocarcinoma 3 13.5
Prostate adenocarcinoma 4 42.3
Prostate NAT 5            12.3
Prostate adenocarcinoma 6 5.0
Prostate adenocarcinoma 7 7.7
Prostate adenocarcinoma 8 2.5
Prostate adenocarcinoma 9 24.3
Prostate NAT 10           4.0
Kidney cancer 1           41.8
Kidney NAT 1              18.6
Kidney cancer 2           100.0
Kidney NAT 2              22.7
Kidney cancer 3           31.2
Kidney NAT 3              13.2
Kidney cancer 4           27.7
Kidney NAT 4              15.4

[0965] CNS_neurodegeneration_v1.0 Summary: Ag805/Ag3770 Two experiments with different probe and primer sets produce results that are in excellent agreement. These panels confirm the expression of this gene at low levels in the brain in an independent group of individuals. This gene appears to be slightly down-regulated in the temporal cortex of Alzheimer's disease patients. Therefore, up-regulation of this gene or its protein product, or treatment with specific agonists for this receptor may be of use in reversing the dementia, memory loss, and neuronal death associated with this disease.

[0966] General_screening_panel_v1.4 Summary: Ag3770 Highest expression of this gene is seen in a gastric cancer cell line (CT=26.7). This gene is widely expressed in this panel, with high to moderate 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.

[0967] 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.

[0968] In addition, this gene is expressed at much higher levels in fetal lung tissue (CT=28.5) when compared to expression in the adult counterpart (CT=32). Thus, expression of this gene may be used to differentiate between the fetal and adult source of this tissue.

[0969] This gene is also expressed at moderate to 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.

[0970] Panel 1.3D Summary: Ag805 Highest expression is in fetal kidney (CT=29.2). This gene is widely expressed in this panel, with moderate to low expression in many samples on this panel. Please see Panel 1.4 for further discussion of expression and utility of this gene.

[0971] Panel 4.1D Summary: Ag805/Ag3770 Two experiments with different probe and primer sets are in good agreements with highest expression of this gene seen in activated secondary Th2 cells and 2 way MLR (CTs=27.6-28). 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.

[0972] general oncology screening panel_v—2.4 Summary: Ag3770 Highest expression is seen in a kidney cancer (CT=29.5). In addition, this gene is more highly expressed in lung, colon and kidney cancer than in the corresponding normal adjacent tissue. Prominent expression is seen in prostate cancer and melanoma as well. 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, colon, prostate, melanoma and kidney cancer.

[0973] AG. CG96334-02: DUAL-SPECIFICITY TYROSINE-PHOSPHORYLATION REGULATED KINASE 1A-Like Gene

[0974] Expression of gene CG96334-02 was assessed using the primer-probe set Ag7413, described in Table AGA. Results of the RTQ-PCR runs are shown in Tables AGB, AGC and AGD.

TABLE AGA
Probe Name Ag7413
			Start
Primers	Sequences	Length	Position	SEQ ID No
Forward	5′-aagcatattaatgaggagtacaa	26	302	329
	acc-3′
Probe	TET-5′-aggaacccgtaaacttcat	30	331	330
	aacattcttgg-3′-TAMRA
Reverse	5′-ccaccaggtcctcctgttt-3′	19	366	331

[0975]

TABLE AGB
CNS_neurodegeneration_v1.0
                               Rel. Exp. (%)
                               Ag7413, Run
Tissue Name                    305064633
AD 1 Hippo                     15.9
AD 2 Hippo                     13.1
AD 3 Hippo                     6.8
AD 4 Hippo                     5.8
AD 5 Hippo                     100.0
AD 6 Hippo                     36.3
Control 2 Hippo                25.9
Control 4 Hippo                14.0
Control (Path) 3 Hippo         11.7
AD 1 Temporal Ctx              18.8
AD 2 Temporal Ctx              41.5
AD 3 Temporal Ctx              3.6
AD 4 Temporal Ctx              13.9
AD 5 Inf Temporal Ctx          76.8
AD 5 Sup Temporal Ctx          28.5
AD 6 Inf Temporal Ctx          40.3
AD 6 Sup Temporal Ctx          43.2
Control 1 Temporal Ctx         3.8
Control 2 Temporal Ctx         51.8
Control 3 Temporal Ctx         12.5
Control 3 Temporal Ctx         11.3
Control (Path) 1 Temporal Ctx  33.0
Control (Path) 2 Temporal Ctx  31.4
Control (Path) 3 Temporal Ctx  4.8
Control (Path) 4 Temporal Ctx  25.0
AD 1 Occipital Ctx             16.6
AD 2 Occipital Ctx (Missing)   0.0
AD 3 Occipital Ctx             5.2
AD 4 Occipital Ctx             13.2
AD 5 Occipital Ctx             45.4
AD 6 Occipital Ctx             21.9
Control 1 Occipital Ctx        3.0
Control 2 Occipital Ctx        55.9
Control 3 Occipital Ctx        15.0
Control 4 Occipital Ctx        6.2
Control (Path) 1 Occipital Ctx 73.7
Control (Path) 2 Occipital Ctx 6.4
Control (Path) 3 Occipital Ctx 3.5
Control (Path) 4 Occipital Ctx 12.4
Control 1 Parietal Ctx         5.8
Control 2 Parietal Ctx         26.8
Control 3 Parietal Ctx         23.2
Control (Path) 1 Parietal Ctx  92.0
Control (Path) 2 Parietal Ctx  11.2
Control (Path) 3 Parietal Ctx  1.9
Control (Path) 4 Parietal Ctx  27.5

[0976]

TABLE AGC
General_screening_panel_v1.6
                                 Rel. Exp. (%)
                                 Ag7413, Run
Tissue Name                      306067377
Adipose                          9.3
Melanoma* Hs688(A).T             15.3
Melanoma* Hs688(B).T             22.5
Melanoma* M14                    38.2
Melanoma* LOXIMVI                35.6
Melanoma* SK-MEL-5               50.0
Squamous cell carcinoma SCC-4    11.4
Testis Pool                      22.2
Prostate ca.* (bone met) PC-3    55.5
Prostate Pool                    11.8
Placenta                         11.4
Uterus Pool                      5.4
Ovarian ca. OVCAR-3              46.0
Ovarian ca. SK-OV-3              42.9
Ovarian ca. OVCAR-4              11.3
Ovarian ca. OVCAR-5              25.2
Ovarian ca. IGROV-1              6.9
Ovarian ca. OVCAR-8              6.7
Ovary                            11.9
Breast ca. MCF-7                 24.7
Breast ca. MDA-MB-231            22.7
Breast ca. BT 549                55.1
Breast ca. T47D                  30.6
Breast ca. MDA-N                 12.5
Breast Pool                      34.4
Trachea                          24.3
Lung                             10.4
Fetal Lung                       77.9
Lung ca. NCI-N417                6.7
Lung ca. LX-1                    34.2
Lung ca. NCI-H146                12.5
Lung ca. SHP-77                  29.3
Lung ca. A549                    21.2
Lung ca. NCI-H526                0.0
Lung ca. NCI-H23                 36.9
Lung ca. NCI-H460                27.7
Lung ca. HOP-62                  13.2
Lung ca. NCI-H522                37.9
Liver                            0.0
Fetal Liver                      37.6
Liver ca. HepG2                  15.6
Kidney Pool                      33.9
Fetal Kidney                     48.6
Renal ca. 786-0                  24.5
Renal ca. A498                   15.2
Renal ca. ACHN                   10.7
Renal ca. UO-31                  16.8
Renal ca. TK-10                  24.1
Bladder                          18.7
Gastric ca. (liver met.) NCI-N87 3.1
Gastric ca. KATO III             40.9
Colon ca. SW-948                 5.0
Colon ca. SW480                  40.9
Colon ca.* (SW480 met) SW620     23.8
Colon ca. HT29                   15.9
Colon ca. HCT-116                30.4
Colon ca. CaCo-2                 49.7
Colon cancer tissue              12.9
Colon ca. SW1116                 6.4
Colon ca. Colo-205               5.8
Colon ca. SW-48                  0.0
Colon Pool                       27.5
Small Intestine Pool             30.1
Stomach Pool                     14.3
Bone Marrow Pool                 12.2
Fetal Heart                      46.3
Heart Pool                       17.0
Lymph Node Pool                  35.8
Fetal Skeletal Muscle            28.7
Skeletal Muscle Pool             10.2
Spleen Pool                      8.6
Thymus Pool                      26.6
CNS cancer (glio/astro) U87-MG   32.8
CNS cancer (glio/astro) U-118-MG 40.3
CNS cancer (neuro; met) SK-N-AS  47.0
CNS cancer (astro) SF-539        32.8
CNS cancer (astro) SNB-75        100.0
CNS cancer (glio) SNB-19         11.9
CNS cancer (glio) SF-295         71.2
Brain (Amygdala) Pool            7.9
Brain (cerebellum)               42.0
Brain (fetal)                    36.6
Brain (Hippocampus) Pool         17.2
Cerebral Cortex Pool             20.6
Brain (Substantia nigra) Pool    11.3
Brain (Thalamus) Pool            26.6
Brain (whole)                    30.6
Spinal Cord Pool                 10.0
Adrenal Gland                    24.5
Pituitary gland Pool             7.1
Salivary Gland                   6.5
Thyroid (female)                 2.4
Pancreatic ca. CAPAN2            15.5
Pancreas Pool                    7.6

[0977]

TABLE AGP
Panel 4.1D
                                 Rel. Exp. (%)
                                 Ag7413, Run
Tissue Name                      305065274
Secondary Th1 act                71.7
Secondary Th2 act                93.3
Secondary Tr1 act                36.6
Secondary Th1 rest               17.1
Secondary Th2 rest               28.7
Secondary Tr1 rest               12.9
Primary Th1 act                  12.9
Primary Th2 act                  68.8
Primary Tr1 act                  56.3
Primary Th1 rest                 6.8
Primary Th2 rest                 10.6
Primary Tr1 rest                 10.4
CD45RA CD4 lymphocyte act        58.6
CD45RO CD4 lymphocyte act        95.3
CD8 lymphocyte act               8.8
Secondary CD8 lymphocyte rest    47.3
Secondary CD8 lymphocyte act     7.6
CD4 lymphocyte none              28.1
2ry Th1/Th2/Tr1_anti-CD95 CH11   20.3
LAK cells rest                   35.4
LAK cells IL-2                   19.8
LAK cells IL-2 + IL-12           2.7
LAK cells IL-2 + IFN gamma       18.3
LAK cells IL-2 + IL-18           9.5
LAK cells PMA/ionomycin          65.1
NK Cells IL-2 rest               72.7
Two Way MLR 3 day                60.3
Two Way MLR 5 day                13.2
Two Way MLR 7 day                15.0
PBMC rest                        22.8
PBMC PWM                         13.4
PBMC PHA-L                       21.5
Ramos (B cell) none              23.5
Ramos (B cell) ionomycin         41.8
B lymphocytes PWM                20.2
B lymphocytes CD40L and IL-4     56.3
EOL-1 dbcAMP                     56.6
EOL-1 dbcAMP PMA/ionomycin       23.7
Dendritic cells none             28.3
Dendritic cells LPS              18.4
Dendritic cells anti-CD40        5.8
Monocytes rest                   16.0
Monocytes LPS                    68.3
Macrophages rest                 11.8
Macrophages LPS                  23.5
HUVEC none                       27.9
HUVEC starved                    30.6
HUVEC IL-1beta                   35.1
HUVEC IFN gamma                  31.9
HUVEC TNF alpha + IFN gamma      26.6
HUVEC TNF alpha + IL4            16.6
HUVEC IL-11                      36.1
Lung Microvascular EC none       45.4
Lung Microvascular EC TNFalpha + IL-1beta 12.5
Microvascular Dermal EC none     16.0
Microsvasular Dermal EC TNFalpha + IL-1beta 7.8
Bronchial epithelium TNFalpha + IL1beta 17.6
Small airway epithelium none     4.0
Small airway epithelium TNFalpha + IL-1beta 21.3
Coronery artery SMC rest         16.4
Coronery artery SMC TNFalpha + IL-1beta 14.2
Astrocytes rest                  9.9
Astrocytes TNFalpha + IL-1beta   22.8
KU-812 (Basophil) rest           60.3
KU-812 (Basophil) PMA/ionomycin  96.6
CCD1106 (Keratinocytes) none     32.3
CCD1106 (Keratinocytes) TNFalpha + IL-1beta 16.0
Liver cirrhosis                  27.2
NCI-H292 none                    36.1
NCI-H292 IL-4                    46.3
NCI-H292 IL-9                    51.4
NCI-H292 IL-13                   46.7
NCI-H292 IFN gamma               44.8
HPAEC none                       15.7
HPAEC TNF alpha + IL-1 beta      34.2
Lung fibroblast none             37.6
Lung fibroblast TNF alpha + IL-1 beta 31.0
Lung fibroblast IL-4             19.1
Lung fibroblast IL-9             57.4
Lung fibroblast IL-13            9.2
Lung fibroblast IFN gamma        22.8
Dermal fibroblast CCD1070 rest   52.5
Dermal fibroblast CCD1070 TNF alpha 94.0
Dermal fibroblast CCD1070 IL-1 beta 21.8
Dermal fibroblast IFN gamma      25.9
Dermal fibroblast IL-4           36.1
Dermal Fibroblasts rest          25.7
Neutrophils TNFa + LPS           41.2
Neutrophils rest                 100.0
Colon                            14.6
Lung                             8.4
Thymus                           39.2
Kidney                           49.3

[0978] CNS_neurodegeneration_v1.0 Summary: Ag7413 This gene is expressed at low levels in 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.

[0979] General_screening_panel_v1.6 Summary: Ag7413 Detectable expression of this gene is limited to two brain cancer cell line samples. Thus, therapeutic modulation of the expression or function of this gene may be effective in the treatment of brain cancer.

[0980] Panel 4.1D Summary: Ag7413 Highest expression of this gene is seen in resting neutrophils (CT=32.9). Low but significant expression is seen in many samples on this panel, including samples derived from T cells, LAK cells, LPS stimulated monocytes and macrohpages, lung and dermal fibroblasts, and normal kidney and thymus. Therefore, therapeutic modulation of this gene or its protein product may be useful in the treatment of autoimmune and inflammatory diseases such as lupus erythematosus, asthma, emphysema, Crohn's disease, ulcerative colitis, rheumatoid arthritis, osteoarthritis, and psoriasis. In addition, small molecule or antibody antagonists of this gene product may be effective in increasing the immune response in patients with AIDS or other immunodeficiencies.

[0981] AH. CG96714-01: UDP-Galactose Transporter Related Isozyme 1-Like Gene

[0982] Expression of gene CG96714-01 was assessed using the primer-probe set Ag4074, described in Table AHA. Results of the RTQ-PCR runs are shown in Tables AHB and AHC.

TABLE AHA
Probe Name Ag4074
			Start
Primers	Sequences	Length	Position	SEQ ID No
Forward	5′-aaggtaccctgccatcatctat-3′	22	789	332
Probe	TET-5′-acatcctgctctttgggctg	26	812	333
	accagt-3′-TAMRA
Reverse	5′-caaccgtcataaagatgaagct-3′	22	850	334

[0983]

TABLE AHB
General_screening_panel_v1.4
                                 Rel. Exp. (%)
                                 Ag4074, Run
Tissue Name                      218906368
Adipose                          2.8
Melanoma* Hs688(A).T             13.7
Melanoma* Hs688(B).T             16.5
Melanoma* M14                    19.8
Melanoma* LOXIMVI                29.9
Melanoma* SK-MEL-5               27.0
Squamous cell carcinoma SCC-4    18.6
Testis Pool                      3.9
Prostate ca.* (bone met) PC-3    82.9
Prostate Pool                    2.6
Placenta                         5.6
Uterus Pool                      1.1
Ovarian ca. OVCAR-3              31.0
Ovarian ca. SK-OV-3              27.4
Ovarian ca. OVCAR-4              11.0
Ovarian ca. OVCAR-5              48.6
Ovarian ca. IGROV-1              28.7
Ovarian ca. OVCAR-8              12.7
Ovary                            2.5
Breast ca. MCF-7                 23.7
Breast ca. MDA-MB-231            30.6
Breast ca. BT 549                8.0
Breast ca. T47D                  100.0
Breast ca. MDA-N                 5.6
Breast Pool                      0.0
Trachea                          7.6
Lung                             1.3
Fetal Lung                       8.5
Lung ca. NCI-N417                5.2
Lung ca. LX-1                    14.2
Lung ca. NCI-H146                9.3
Lung ca. SHP-77                  25.9
Lung ca. A549                    29.1
Lung ca. NCI-H526                8.4
Lung ca. NCI-H23                 18.6
Lung ca. NCI-H460                21.9
Lung ca. HOP-62                  15.9
Lung ca. NCI-H522                34.9
Liver                            2.7
Fetal Liver                      11.7
Liver ca. HepG2                  12.2
Kidney Pool                      4.8
Fetal Kidney                     7.7
Renal ca. 786-0                  6.7
Renal ca. A498                   5.9
Renal ca. ACHN                   9.8
Renal ca. UO-31                  10.7
Renal ca. TK-10                  20.2
Bladder                          10.8
Gastric ca. (liver met.) NCI-N87 38.7
Gastric ca. KATO III             62.9
Colon ca. SW-948                 12.2
Colon ca. SW480                  16.6
Colon ca.* (SW480 met) SW620     16.0
Colon ca. HT29                   9.2
Colon ca. HCT-116                55.5
Colon ca. CaCo-2                 71.7
Colon cancer tissue              11.0
Colon ca. SW1116                 6.1
Colon ca. Colo-205               11.5
Colon ca. SW-48                  6.3
Colon Pool                       4.3
Small Intestine Pool             3.1
Stomach Pool                     2.6
Bone Marrow Pool                 1.9
Fetal Heart                      7.5
Heart Pool                       3.2
Lymph Node Pool                  4.4
Fetal Skeletal Muscle            4.9
Skeletal Muscle Pool             9.0
Spleen Pool                      3.1
Thymus Pool                      4.3
CNS cancer (glio/astro) U87-MG   43.8
CNS cancer (glio/astro) U-118-MG 25.5
CNS cancer (neuro; met) SK-N-AS  30.6
CNS cancer (astro) SF-539        16.4
CNS cancer (astro) SNB-75        21.3
CNS cancer (glio) SNB-19         25.3
CNS cancer (glio) SF-295         44.1
Brain (Amygdala) Pool            4.9
Brain (cerebellum)               9.4
Brain (fetal)                    6.3
Brain (Hippocampus) Pool         4.5
Cerebral Cortex Pool             5.8
Brain (Substantia nigra) Pool    5.4
Brain (Thalamus) Pool            7.2
Brain (whole)                    0.0
Spinal Cord Pool                 3.8
Adrenal Gland                    5.6
Pituitary gland Pool             3.6
Salivary Gland                   5.2
Thyroid (female)                 6.3
Pancreatic ca. CAPAN2            6.4
Pancreas Pool                    3.9

[0984]

TABLE AHC
Panel 5D
                                 Rel. Exp. (%)
                                 Ag4074, Run
Tissue Name                      172166872
97457_Patient-02go_adipose       15.4
97476_Patient-07sk_skeletal muscle 9.3
97477_Patient-07ut_uterus        10.7
97478_Patient-07pl_placenta      36.3
97481_Patient-08sk_skeletal muscle 8.8
97482_Patient-08ut_uterus        8.4
97483_Patient-08pl_placenta      43.5
97486_Patient-09sk_skeletal muscle 7.9
97487_Patient-09ut_uterus        8.5
97488_Patient-09pl_placenta      16.5
97492_Patient-10ut_uterus        14.2
97493_Patient-10pl_placenta      58.6
97495_Patient-11go_adipose       8.8
97496_Patient-11sk_skeletal muscle 29.5
97497_Patient-11ut_uterus        17.1
97498_Patient-11pl_placenta      39.5
97500_Patient-12go_adipose       17.9
97501_Patient-12sk_skeletal muscle 72.7
97502_Patient-12ut_uterus        17.6
97503_Patient-12pl_placenta      26.4
94721_Donor 2 U - A_Mesenchymal Stem Cells 36.6
94722_Donor 2 U - B_Mesenchymal Stem Cells 22.5
94723_Donor 2 U - C_Mesenchymal Stem Cells 27.5
94709_Donor 2 AM - A_adipose     100.0
94710_Donor 2 AM - B_adipose     62.4
94711_Donor 2 AM - C_adipose     39.8
94712_Donor 2 AD - A_adipose     37.9
94713_Donor 2 AD - B_adipose     58.2
94714_Donor 2 AD - C adipose     42.9
94742_Donor 3 U - A_Mesenchymal Stem Cells 27.4
94743_Donor 3 U - B_Mesenchymal Stem Cells 24.5
94730_Donor 3 AM - A_adipose     88.3
94731_Donor 3 AM - B_adipose     45.1
94732_Donor 3 AM - C_adipose     60.7
94733_Donor 3 AD - A_adipose     88.3
94734_Donor 3 AD - B_adipose     43.2
94735_Donor 3 AD - C_adipose     79.6
77138_Liver_HepG2untreated       93.3
73556_Heart_Cardiac stromal cells (primary) 40.3
81735_Small Intestine            23.7
72409_Kidney_Proximal Convoluted Tubule 19.2
82685_Small intestine_Duodenum   40.6
90650_Adrenal_Adrenocortical adenoma 10.4
72410_Kidney_HRCE                49.3
72411_Kidney_HRE                 49.0
73139_Uterus_Uterine smooth muscle cells 21.9

[0985] General_screening_panel_v1.4 Summary: Ag4074 Highest expression of this gene is detected in breast cancer T47D cell line (CT=26). High levels of expression of this gene is also seen in cluster of cell lines derived from pancreatic, gastric, colon, lung, liver, 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, liver, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers.

[0986] 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.

[0987] 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.

[0988] Panel 5D Summary: Ag4074 Highest expression of this gene is detected in adipose (CT-30). Consistent with expression seen in panel 1.4, this gene shows ubiquitous expression in this panel. Please see panel 1.4 for further discussion on the utility of this gene.

[0989] AI. CG97025-01: HMG-CoA Synthase-Like Gene

[0990] Expression of gene CG97025-01 was assessed using the primer-probe set Ag4087, described in Table AIA. Results of the RTQ-PCR runs are shown in Tables AIB, AIC, AID, AIE, AIF, AIG and AIH.

TABLE AIA
Probe Name Ag4087
			Start
Primers	Sequences	Length	Position	SEQ ID No
Forward	5′-ttcagtatatggttcccttgca-3′	22	1062	335
Probe	TET-5′-tgttctagcacagtactcac	27	1086	336
	ctcagca-3′-TAMRA
Reverse	5′-actccaattctcttccctgcta-3′	22	1115	337

[0991]

TABLE AIB
CNS_neurodegeneration_v1.0
                               Rel. Exp. (%)
                               Ag4087, Run
Tissue Name                    214295439
AD 1 Hippo                     8.4
AD 2 Hippo                     19.2
AD 3 Hippo                     2.3
AD 4 Hippo                     4.7
AD 5 hippo                     38.2
AD 6 Hippo                     100.0
Control 2 Hippo                27.2
Control 4 Hippo                8.7
Control (Path) 3 Hippo         2.8
AD 1 Temporal Ctx              5.7
AD 2 Temporal Ctx              27.5
AD 3 Temporal Ctx              2.2
AD 4 Temporal Ctx              17.9
AD 5 Inf Temporal Ctx          54.0
AD 5 Sup Temporal Ctx          13.5
AD 6 Inf Temporal Ctx          72.7
AD 6 Sup Temporal Ctx          87.7
Control 1 Temporal Ctx         3.4
Control 2 Temporal Ctx         25.9
Control 3 Temporal Ctx         10.2
Control 4 Temporal Ctx         5.8
Control (Path) 1 Temporal Ctx  54.0
Control (Path) 2 Temporal Ctx  49.7
Control (Path) 3 Temporal Ctx  2.3
Control (Path) 4 Temporal Ctx  23.0
AD 1 Occipital Ctx             5.5
AD 2 Occipital Ctx (Missing)   0.0
AD 3 Occipital Ctx             2.5
AD 4 Occipital Ctx             15.6
AD 5 Occipital Ctx             50.7
AD 6 Occipital Ctx             22.5
Control 1 Occipital Ctx        1.4
Control 2 Occipital Ctx        29.9
Control 3 Occipital Ctx        10.0
Control 4 Occipital Ctx        4.2
Control (Path) 1 Occipital Ctx 82.4
Control (Path) 2 Occipital Ctx 10.6
Control (Path) 3 Occipital Ctx 1.1
Control (Path) 4 Occipital Ctx 9.2
Control 1 Parietal Ctx         3.5
Control 2 Parietal Ctx         18.7
Control 3 Parietal Ctx         14.7
Control (Path) 1 Parietal Ctx  72.2
Control (Path) 2 Parietal Ctx  23.2
Control (Path) 3 Parietal Ctx  1.8
Control (Path) 4 Parietal Ctx  23.2

[0992]

TABLE AIC
General_screening_panel_v1.4
                                 Rel. Exp. (%)
                                 Ag4087, Run
Tissue Name                      219430028
Adipose                          2.3
Melanoma* Hs688(A).T             3.2
Melanoma* Hs688(B).T             8.8
Melanoma* M14                    18.6
Melanoma* LOXIMVI                4.4
Melanoma* SK-MEL-5               21.6
Squamous cell carcinoma SCC-4    39.5
Testis Pool                      6.2
Prostate ca.* (bone met) PC-3    6.8
Prostate Pool                    0.6
Placenta                         1.3
Uterus Pool                      2.0
Ovarian ca. OVCAR-3              80.7
Ovarian ca. SK-OV-3              26.6
Ovarian ca. OVCAR-4              7.1
Ovarian ca. OVCAR-5              31.4
Ovarian ca. IGROV-1              58.6
Ovarian ca. OVCAR-8              3.5
Ovary                            11.4
Breast ca. MCF-7                 17.9
Breast ca. MDA-MB-231            12.9
Breast ca. BT 549                38.7
Breast ca. T47D                  55.9
Breast ca. MDA-N                 7.9
Breast Pool                      2.4
Trachea                          3.8
Lung                             1.2
Fetal Lung                       9.9
Lung ca. NCI-N417                22.4
Lung ca. LX-1                    16.8
Lung ca. NCI-H146                28.5
Lung ca. SHP-77                  36.6
Lung ca. A549                    25.2
Lung ca. NCI-H526                25.7
Lung ca. NCI-H23                 16.7
Lung ca. NCI-H460                4.5
Lung ca. HOP-62                  23.0
Lung ca. NCI-H522                9.2
Liver                            1.3
Fetal Liver                      100.0
Liver ca. HepG2                  50.7
Kidney Pool                      6.0
Fetal Kidney                     8.8
Renal ca. 786-0                  31.0
Renal ca. A498                   4.1
Renal ca. ACHN                   20.9
Renal ca. UO-31                  18.6
Renal ca. TK-10                  24.7
Bladder                          17.6
Gastric ca. (liver met.) NCI-N87 23.3
Gastric ca. KATO III             79.6
Colon ca. SW-948                 14.2
Colon ca. SW480                  10.7
Colon ca.* (SW480 met) SW620     9.5
Colon ca. HT29                   20.4
Colon ca. HCT-116                24.8
Colon ca. CaCo-2                 63.3
Colon cancer tissue              5.0
Colon ca. SW1116                 3.3
Colon ca. Colo-205               10.2
Colon ca. SW-48                  7.9
Colon Pool                       2.8
Small Intestine Pool             3.2
Stomach Pool                     2.7
Bone Marrow Pool                 1.2
Fetal Heart                      4.1
Heart Pool                       1.5
Lymph Node Pool                  2.9
Fetal Skeletal Muscle            0.2
Skeletal Muscle Pool             2.4
Spleen Pool                      4.4
Thymus Pool                      3.3
CNS cancer (glio/astro) U87-MG   10.4
CNS cancer (glio/astro) U-118-MG 8.7
CNS cancer (neuro; met) SK-N-AS  19.3
CNS cancer (astro) SF-539        42.9
CNS cancer (astro) SNB-75        26.1
CNS cancer (glio) SNB-19         51.8
CNS cancer (glio) SF-295         11.4
Brain (Amygdala) Pool            11.3
Brain (cerebellum)               3.3
Brain (fetal)                    52.5
Brain (Hippocampus) Pool         17.7
Cerebral Cortex Pool             17.8
Brain (Substantia nigra) Pool    15.9
Brain (Thalamus) Pool            26.2
Brain (whole)                    14.9
Spinal Cord Pool                 13.2
Adrenal Gland                    23.0
Pituitary gland Pool             1.2
Salivary Gland                   0.8
Thyroid (female)                 2.1
Pancreatic ca. CAPAN2            56.6
Pancreas Pool                    4.9

[0993]

TABLE AID
Panel 3D
                                 Rel. Exp. (%)
                                 Ag4087, Run
Tissue Name                      184795547
Daoy- Medulloblastoma            3.3
TE671- Medulloblastoma           8.3
D283 Med- Medulloblastoma        10.4
PFSK-1- Primitive Neuroectodermal 4.9
XF-498- CNS                      4.4
SNB-78- Glioma                   4.8
SF-268- Glioblastoma             4.1
T98G- Glioblastoma               6.9
SK-N-SH- Neuroblastoma (metastasis) 2.0
SF-295- Glioblastoma             2.1
Cerebellum                       5.8
Cerebellum                       1.7
NCI-H292- Mucoepidermoid lung carcinoma 13.9
DMS-114- Small cell lung cancer  4.5
DMS-79- Small cell lung cancer   100.0
NCI-H146- Small cell lung cancer 57.0
NCI-H526- Small cell lung cancer 54.3
NCI-N417- Small cell lung cancer 34.9
NCI-H82- Small cell lung cancer  10.9
NCI-H157- Squamous cell lung cancer (metastasis) 2.4
NCI-H1155- Large cell lung cancer 7.9
NCI-H1299- Large cell lung cancer 4.1
NCI-H727- Lung carcinoid         11.2
NCI-UMC-11- Lung carcinoid       76.8
LX-1- Small cell lung cancer     13.0
Colo-205- Colon cancer           17.4
KM12- Colon cancer               9.1
KM20L2- Colon cancer             5.6
NCI-H716- Colon cancer           10.6
SW-48- Colon adenocarcinoma      7.5
SW1116- Colon adenocarcinoma     2.4
LS 174T- Colon adenocarcinoma    11.4
SW-948- Colon adenocarcinoma     1.0
SW-480- Colon adenocarcinoma     6.7
NCI-SNU-5- Gastric carcinoma     1.2
KATO III- Gastric carcinoma      28.3
NCI-SNU-16- Gastric carcinoma    1.7
NCI-SNU-1- Gastric carcinoma     70.2
RF-1- Gastric adenocarcinoma     11.5
RF-48- Gastric adenocarcinoma    8.5
MKN-45- Gastric carcinoma        11.4
NCI-N87- Gastric carcinoma       8.6
OVCAR-5- Ovarian carcinoma       1.5
RL95-2- Uterine carcinoma        2.2
HelaS3- Cervical adenocarcinoma  1.2
Ca Ski- Cervical epidermoid carcinoma 26.2
(metastasis)
ES-2- Ovarian clear cell carcinoma 1.5
Ramos- Stimulated with PMA/ionomycin 6 h 37.9
Ramos- Stimulated with PMA/ionomycin 14 h 24.8
MEG-01- Chronic myelogenous leukemia 10.1
(megokaryoblast)
Raji- Burkitt's lymphoma         6.7
Daudi- Burkitt's lymphoma        22.5
U266- B-cell plasmacytoma        9.6
CA46- Burkitt's lymphoma         10.4
RL- non-Hodgkin's B-cell lymphoma 7.5
JM1- pre-B-cell lymphoma         7.1
Jurkat- T cell leukemia          37.4
TF-1- Erythroleukemia            31.6
HUT 78- T-cell lymphoma          5.3
U937- Histiocytic lymphoma       5.3
KU-812- Myelogenous leukemia     20.4
769-P- Clear cell renal carcinoma 4.5
Caki-2- Clear cell renal carcinoma 5.7
SW 839- Clear cell renal carcinoma 4.6
G401- Wilms' tumor               5.0
Hs766T- Pancreatic carcinoma (LN metastasis) 2.6
CAPAN-1- Pancreatic adenocarcinoma 17.0
(liver metastasis)
SU86.86- Pancreatic carcinoma (liver metastasis) 20.0
BxPC-3- Pancreatic adenocarcinoma 15.0
HPAC- Pancreatic adenocarcinoma  80.1
MIA PaCa-2- Pancreatic carcinoma 1.2
CFPAC-1- Pancreatic ductal adenocarcinoma 24.7
PANC-1- Pancreatic epithelioid ductal carcinoma 4.2
T24- Bladder carcinma (transitional cell) 4.2
5637- Bladder carcinoma          6.0
HT-1197- Bladder carcinoma       14.8
UM-UC-3- Bladder carcinma (transitional cell) 1.8
A204- Rhabdomyosarcoma           0.9
HT-1080- Fibrosarcoma            9.3
MG-63- Osteosarcoma              2.6
SK-LMS-1- Leiomyosarcoma (vulva) 6.3
SJRH30- Rhabdomyosarcoma (met to bone marrow) 5.1
A431- Epidermoid carcinoma       6.9
WM266-4- Melanoma                1.0
DU 145- Prostate carcinoma (brain metastasis) 0.7
MDA-MB-468- Breast adenocarcinoma 9.8
SCC-4- Squamous cell carcinoma of tongue 1.6
SCC-9- Squamous cell carcinoma of tongue 0.2
SCC-15- Squamous cell carcinoma of tongue 0.5
CAL 27- Squamous cell carcinoma of tongue 7.5

[0994]

TABLE AIE
Panel 4.1D
                                 Rel. Exp. (%)
                                 Ag4087, Run
Tissue Name                      184793001
Secondary Th1 act                34.2
Secondary Th2 act                32.8
Secondary Tr1 act                27.0
Secondary Th1 rest               10.0
Secondary Th2 rest               13.4
Secondary Tr1 rest               10.3
Primary Th1 act                  26.6
Primary Th2 act                  68.8
Primary Tr1 act                  66.9
Primary Th1 rest                 8.2
Primary Th2 rest                 2.7
Primary Tr1 rest                 10.7
CD45RA CD4 lymphocyte act        24.1
CD45RO CD4 lymphocyte act        55.5
CD8 lymphocyte act               33.0
Secondary CD8 lymphocyte rest    37.1
Secondary CD8 lymphocyte act     15.6
CD4 lymphocyte none              1.4
2ry Th1/Th2/Tr1_anti-CD95 CH11   8.1
LAK cells rest                   32.3
LAK cells IL-2                   40.3
LAK cells IL-2 + IL-12           11.7
LAK cells IL-2 + IFN gamma       10.5
LAK cells IL-2 + IL-18           13.3
LAK cells PMA/ionomycin          83.5
NK Cells IL-2 rest               33.7
Two Way MLR 3 day                10.9
Two Way MLR 5 day                10.6
Two Way MLR 7 day                10.7
PBMC rest                        2.0
PBMC PWM                         27.0
PBMC PHA-L                       19.6
Ramos (B cell) none              45.1
Ramos (B cell) ionomycin         68.8
B lymphocytes PWM                25.2
B lymphocytes CD40L and IL-4     22.1
EOL-1 dbcAMP                     8.4
EOL-1 dbcAMP PMA/ionomycin       18.4
Dendritic cells none             28.9
Dendritic cells LPS              20.9
Dendritic cells anti-CD40        7.5
Monocytes rest                   4.0
Monocytes LPS                    26.4
Macrophages rest                 13.0
Macrophages LPS                  5.8
HUVEC none                       19.3
HUVEC starved                    34.6
HUVEC IL-1beta                   27.0
HUVEC IFN gamma                  21.0
HUVEC TNF alpha + IFN gamma      20.2
HUVEC TNF alpha + IL4            17.9
HUVEC IL-11                      12.8
Lung Microvascular EC none       23.3
Lung Microvascular EC TNFalpha + IL-1beta 19.9
Microvascular Dermal EC none     5.1
Microsvasular Dermal EC TNFalpha + IL-1beta 11.1
Bronchial epithelium TNFalpha + IL1beta 40.9
Small airway epithelium none     16.0
Small airway epithelium TNFalpha + IL-1beta 100.0
Coronery artery SMC rest         2.5
Coronery artery SMC TNFalpha + IL-1beta 3.7
Astrocytes rest                  4.3
Astrocytes TNFalpha + IL-1beta   5.5
KU-812 (Basophil) rest           39.8
KU-812 (Basophil) PMA/ionomycin  95.3
CCD1106 (Keratinocytes) none     79.6
CCD1106 (Keratinocytes) TNFalpha + IL-1beta 59.0
Liver cirrhosis                  4.8
NCI-H292 none                    10.2
NCI-H292 IL-4                    12.5
NCI-H292 IL-9                    18.4
NCI-H292 IL-13                   14.8
NCI-H292 IFN gamma               9.2
HPAEC none                       4.8
HPAEC TNF alpha + IL-1 beta      24.5
Lung fibroblast none             17.7
Lung fibroblast TNF alpha + IL-1 beta 3.9
Lung fibroblast IL-4             18.3
Lung fibroblast IL-9             20.2
Lung fibroblast IL-13            11.7
Lung fibroblast IFN gamma        10.0
Dermal fibroblast CCD1070 rest   4.4
Dermal fibroblast CCD1070 TNF alpha 19.6
Dermal fibroblast CCD1070 IL-1 beta 3.7
Dermal fibroblast IFN gamma      6.7
Dermal fibroblast IL-4           30.4
Dermal Fibroblasts rest          13.9
Neutrophils TNFa + LPS           3.3
Neutrophils rest                 1.4
Colon                            2.6
Lung                             4.0
Thymus                           4.0
Kidney                           5.3

[0995]

TABLE AIF
Panel 5 Islet
                                 Rel.Exp. (%)
                                 Ag4087, Run
Tissue Name                      186511156
97457_Patient-02go_adipose       1.8
97476_Patient-07sk_skeletal muscle 2.3
97477_Patient-07ut_uterus        3.6
97478_Patient-07pl_placenta      5.5
99167_Bayer Patient 1            13.8
97482_Patient-08ut_uterus        1.3
97483_Patient-08pl_placenta      4.5
97486_Patient-09sk_skeletal muscle 0.4
97487_Patient-09ut_uterus        3.0
97488_Patient-09pl_placenta      3.5
97492_Patient-10ut_uterus        2.7
97493_Patient-10pl_placenta      12.6
97495_Patient-11go_adipose       2.2
97496_Patient-11sk_skeletal muscle 2.9
97497_Patient-11ut_uterus        4.5
97498_Patient-11pl_placenta      3.3
97500_Patient-12go_adipose       5.2
97501_Patient-12sk_skeletal muscle 6.2
97502_Patient-12ut_uterus        4.7
97503_Patient-12pl_placenta      6.2
94721_Donor 2 U - A_Mesenchymal Stem Cells 7.9
94722_Donor 2 U - B_Mesenchymal Stem Cells 5.0
94723_Donor 2 U - C_Mesenchymal Stem Cells 9.5
94709_Donor 2 AM - A_adipose     10.6
94710_Donor 2 AM - B_adipose     7.2
94711_Donor 2 AM - C_adipose     2.6
94712_Donor 2 AD - A_adipose     14.0
94713_Donor 2 AD - B_adipose     13.7
94714_Donor 2 AD - C_adipose     14.8
94742_Donor 3 U - A_Mesenchymal Stem Cells 7.2
94743_Donor 3 U - B_Mesenchymal Stem Cells 8.5
94730_Donor 3 AM - A_adipose     12.9
94731_Donor 3 AM - B_adipose     7.9
94732_Donor 3 AM - C_adipose     7.7
94733_Donor 3 AD - A_adipose     28.9
94734_Donor 3 AD - B_adipose     5.6
94735_Donor 3 AD - C_adipose     23.8
77138_Liver_HepG2untreated       100.0
73556_Heart_Cardiac stromal cells (primary) 2.9
81735_Small Intestine            10.3
72409_Kidney_Proximal Convoluted Tubule 8.8
82685_Small intestine_Duodenum   1.8
90650_Adrenal_Adrenocortical adenoma 10.2
72410_Kidney_HRCE                42.6
72411_Kidney_HRE                 38.2
73139_Uterus_Uterine smooth muscle cells 4.7

[0996]

TABLE AIG
Panel 5D
                                 Rel. Exp. (%)
                                 Ag4087, Run
Tissue Name                      172774941
97457_Patient-02go_adipose       1.7
97476_Patient-07sk_skeletal muscle 2.1
97477_Patient-07ut_uterus        1.2
97478_Patient-07pl_placenta      4.4
97481_Patient-08sk_skeletal muscle 1.9
97482_Patient-08ut_uterus        1.9
97483_Patient-08pl_placenta      2.6
97486_Patient-09sk_skeletal muscle 0.8
97487_Patient-09ut_uterus        2.0
97488_Patient-09pl_placenta      3.1
97492_Patient-10ut_uterus        1.6
97493_Patient-10pl_placenta      8.5
97495_Patient-11go_adipose       2.1
97496_Patient-11sk_skeletal muscle 2.2
97497_Patient-11ut_uterus        3.5
97498_Patient-11pl_placenta      4.4
97500_Patient-12go_adipose       3.3
97501_Patient-12sk_skeletal muscle 3.5
97502_Patient-12ut_uterus        3.6
97503_Patient-12pl_placenta      4.5
94721_Donor 2 U - A_Mesenchymal Stem Cells 7.4
94722_Donor 2 U - B_Mesenchymal Stem Cells 5.5
94723_Donor 2 U - C_Mesenchymal Stem Cells 4.7
94709_Donor 2 AM - A_adipose     11.1
94710_Donor 2 AM - B_adipose     4.7
94711_Donor 2 AM - C_adipose     4.3
94712_Donor 2 AD - A_adipose     9.1
94713_Donor 2 AD - B_adipose     16.0
94714_Donor 2 AD - C_adipose     12.2
94742_Donor 3 U - A_Mesenchymal Stem Cells 5.6
94743_Donor 3 U - B_Mesenchymal Stem Cells 6.0
94730_Donor 3 AM - A_adipose     9.5
94731_Donor 3 AM - B_adipose     5.9
94732_Donor 3 AM - C_adipose     7.0
94733_Donor 3 AD - A_adipose     23.7
94734_Donor 3 AD - B_adipose     11.6
94735_Donor 3 AD - C_adipose     14.7
77138_Liver_HepG2untreated       100.0
73556_Heart_Cardiac stromal cells (primary) 1.3
81735_Small Intestine            4.1
72409_Kidney_Proximal Convoluted Tubule 4.7
82685_Small intestine_Duodenum   9.1
90650_Adrenal_Adrenocortical adenoma 5.7
72410_Kidney_HRCE                22.1
72411_Kidney_HRE                 34.9
73139_Uterus_Uterine smooth muscle cells 4.2

[0997]

TABLE AIH
general oncology screening panel_v_2.4
                          Rel. Exp. (%)
                          Ag4087, Run
Tissue Name               268389980
Colon cancer 1            50.0
Colon NAT 1               16.2
Colon cancer 2            26.8
Colon NAT 2               11.3
Colon cancer 3            52.1
Colon NAT 3               31.6
Colon malignant cancer 4  81.8
Colon NAT 4               12.1
Lung cancer 1             12.6
Lung NAT 1                1.2
Lung cancer 2             95.9
Lung NAT 2                2.2
Squamous cell carcinoma 3 66.0
Lung NAT 3                5.4
Metastatic melanoma 1     11.3
Melanoma 2                8.1
Melanoma 3                10.3
Metastatic melanoma 4     40.1
Metastatic melanoma 5     31.0
Bladder cancer 1          1.1
Bladder NAT 1             0.0
Bladder cancer 2          1.6
Bladder NAT 2             0.3
Bladder NAT 3             0.3
Bladder NAT 4             2.2
Prostate adenocarcinoma 1 14.6
Prostate adenocarcinoma 2 2.1
Prostate adenocarcinoma 3 12.1
Prostate adenocarcinoma 4 19.6
Prostate NAT 5            3.7
Prostate adenocarcinoma 6 3.2
Prostate adenocarcinoma 7 4.7
Prostate adenocarcinoma 8 2.7
Prostate adenocarcinoma 9 14.3
Prostate NAT 10           1.8
Kidney cancer 1           15.7
Kidney NAT 1              10.2
Kidney cancer 2           100.0
Kidney NAT 2              23.8
Kidney cancer 3           15.1
Kidney NAT 3              5.1
Kidney cancer 4           14.1
Kidney NAT 4              8.2

[0998] CNS_neurodegeneration_v1.0 Summary: Ag4087 This panel does not show differential expression of this gene in Alzheimer's disease. However, this profile confirms the expression of this gene at high to moderate levels in the brain. Please see Panel 1.4 for discussion of utility of this gene in the central nervous system.

[0999] General_screening_panel_v1.4 Summary: Ag4087 Highest expression of this gene is seen in fetal liver (CT=22.8). In addition, this gene is expressed at higher levels in fetal lung(CT=26) when compared to expression in the adult counterparts (CTs=29). Conversely, this gene is more highly expressed in skeletal muscle (CT=28) when compared to expression in the fetal tissue (CT=32). Thus, expression of this gene could be used to differentiate between the fetal and adult sources of these tissues.

[1000] 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.

[1001] 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.

[1002] This gene codes for cytosolic HMG CoA synthase. Using CuraGen's GeneCalling TM method of differential gene expression, expression of this gene was found to be up-regulated in two different rodent models of obesity. HMG CoA synthase is an enzyme in the cholesterol biosynthetic pathway and provides substrate for production of LXR alpha activators (ligands). LXRalpha is a nuclear receptor that is abundantly expressed in tissues associated with lipid metabolism. Under high cholesterol conditions, LXR alpha is activated. It in turn, up-regulates transcription of sterol regulatory element-binding protein 1c, the master regulator of genes involved in fatty acid synthesis. Increased production of LXRalpha ligands may lead to increased fatty acid synthesis and triglyceride formation and an increase in adipose mass. Therefore, therapeutic modulation of this gene may be useful in the treatment of obesity.

[1003] 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.

[1004] Panel 3D Summary: Ag4087 Highest expression is seen in a lung cancer cell line (CT=26) with high to moderate levels of expression in all samples on this panel. This expression is in agreement with expression in 1.4.

[1005] Panel 4.1D Summary: Ag4087 Highest expression is seen in TNF-a and IL-1 beta treated small airway epithelium (CT=26). 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.

[1006] Panel 5 Islet Summary: Ag4087 Highest expression is seen in a liver cell line (CT=27.8). In addition this cytosolic HMG CoA synthase has widespread tissue expression including adipose, skeletal muscle, and islets of Langerhans. Recently, it has been shown that upregulation of HMG CoA synthase is associated with the insulin secretory response of islet beta cells to high glucose (Flamez et al., 2002, Diabetes 51(7):2018-24, PMID: 12086928). Thus, pharmacologic activation of this gene may be a treatment to enhance insulin secretion in Type 2 diabetes.

[1007] Panel 5D Summary: Ag4087 Highest expression is seen in a liver cell line (CT=27.5). In addition this cytosolic HMG CoA synthase has widespread tissue expression including adipose, skeletal muscle, and islets of Langerhans.

[1008] general oncology screening panel_v—2.4 Summary: AG4087 Highest expression is seen in a kidney cancer (CT=27). ). In addition, this gene is more highly expressed in lung and colon cancer than in the corresponding normal adjacent tissue. 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, colon and kidney cancer.

[1009] 5 AJ. CG97955-03: Carboxypeptidase A1

[1010] Expression of full-length physical clone CG97955-03 was assessed using the primer-probe set Ag4135, described in Table AJA. Results of the RTQ-PCR runs are shown in Tables AJB, AJC and AJD.

TABLE AJA
Probe Name Ag4135
			Start	SEQ
Primers	Sequences	Length	Position	ID No
Forward	5'-ccctggaggagat-	22	393	338
	ctatgactt-3'
Probe	TET-5'-agaacccgc-	25	435	339
	accttgtc
	agcaagat-3'-TAMRA
Reverse	5'-cttcataggtgtt-	22	461	340
	gccaatctg-3'

[1011]

TABLE AJB
General_screening_panel_v1.4
                                 Rel. Exp. (%)
                                 Ag4135, Run
Tissue Name                      220967144
Adipose                          0.0
Melanoma* Hs688(A).T             0.0
Melanoma* Hs688(B).T             0.0
Melanoma* M14                    0.0
Melanoma* LOXIMVI                0.0
Melanoma* SK-MEL-5               0.0
Squamous cell carcinoma SCC-4    0.0
Testis Pool                      0.0
Prostate ca.* (bone met) PC-3    0.0
Prostate Pool                    0.0
Placenta                         0.0
Uterus Pool                      0.0
Ovarian ca. OVCAR-3              0.0
Ovarian ca. SK-OV-3              0.0
Ovarian ca. OVCAR-4              0.0
Ovarian ca. OVCAR-5              0.0
Ovarian ca. IGROV-1              0.0
Ovarian ca. OVCAR-8              0.0
Ovary                            0.0
Breast ca. MCF-7                 0.0
Breast ca. MDA-MB-231            0.0
Breast ca. BT 549                0.0
Breast ca. T47D                  0.0
Breast ca. MDA-N                 0.0
Breast Pool                      0.0
Trachea                          0.0
Lung                             0.0
Fetal Lung                       0.0
Lung ca. NCI-N417                0.0
Lung ca. LX-1                    0.0
Lung ca. NCI-H146                0.0
Lung ca. SHP-77                  0.0
Lung ca. A549                    0.0
Lung ca. NCI-H526                0.0
Lung ca. NCI-H23                 0.0
Lung ca. NCI-H460                0.0
Lung ca. HOP-62                  0.0
Lung ca. NCI-H522                0.0
Liver                            0.0
Fetal Liver                      1.8
Liver ca. HepG2                  0.0
Kidney Pool                      0.0
Fetal Kidney                     0.0
Renal ca. 786-0                  0.0
Renal ca. A498                   0.0
Renal ca. ACHN                   0.0
Renal ca. UO-31                  0.0
Renal ca. TK-10                  0.0
Bladder                          85.3
Gastric ca. (liver met.) NCI-N87 0.0
Gastric ca. KATO III             0.0
Colon ca. SW-948                 0.0
Colon ca. SW480                  0.0
Colon ca.* (SW480 met) SW620     0.0
Colon ca. HT29                   0.0
Colon ca. HCT-116                0.0
Colon ca. CaCo-2                 0.0
Colon cancer tissue              0.0
Colon ca. SW1116                 0.0
Colon ca. Colo-205               0.0
Colon ca. SW-48                  0.0
Colon Pool                       0.0
Small Intestine Pool             0.0
Stomach Pool                     0.0
Bone Marrow Pool                 0.0
Fetal Heart                      0.0
Heart Pool                       0.0
Lymph Node Pool                  0.0
Fetal Skeletal Muscle            0.0
Skeletal Muscle Pool             0.0
Spleen Pool                      0.0
Thymus Pool                      0.0
CNS cancer (glio/astro) U87-MG   0.0
CNS cancer (glio/astro) U-118-MG 0.0
CNS cancer (neuro; met) SK-N-AS  0.0
CNS cancer (astro) SF-539        0.0
CNS cancer (astro) SNB-75        0.0
CNS cancer (glio) SNB-19         0.0
CNS cancer (glio) SF-295         0.0
Brain (Amygdala) Pool            0.0
Brain (cerebellum)               0.0
Brain (fetal)                    0.0
Brain (Hippocampus) Pool         0.0
Cerebral Cortex Pool             0.0
Brain (Substantia nigra) Pool    0.0
Brain (Thalamus) Pool            0.0
Brain (whole)                    0.0
Spinal Cord Pool                 0.0
Adrenal Gland                    0.0
Pituitary gland Pool             0.0
Salivary Gland                   0.0
Thyroid (female)                 0.0
Pancreatic ca. CAPAN2            0.0
Pancreas Pool                    100.0

[1012]

TABLE AJC
Panel 4.1D
                                 Rel. Exp. (%)
                                 Ag4135, Run
Tissue Name                      172859879
Secondary Th1 act                0.0
Secondary Th2 act                0.0
Secondary Tr1 act                0.0
Secondary Th1 rest               0.0
Secondary Th2 rest               0.0
Secondary Tr1 rest               0.0
Primary Th1 act                  0.0
Primary Th2 act                  0.0
Primary Tr1 act                  0.0
Primary Th1 rest                 3.1
Primary Th2 rest                 0.0
Primary Tr1 rest                 0.0
CD45RA CD4 lymphocyte act        0.0
CD45RO CD4 lymphocyte act        0.0
CD8 lymphocyte act               0.0
Secondary CD8 lymphocyte rest    0.0
Secondary CD8 lymphocyte act     0.0
CD4 lymphocyte none              0.0
2ry Th1/Th2/Tr1_anti-CD95 CH11   0.0
LAK cells rest                   0.0
LAK cells IL-2                   0.0
LAK cells IL-2 + IL-12           0.0
LAK cells IL-2 + IFN gamma       0.0
LAK cells IL-2 + IL-18           0.0
LAK cells PMA/ionomycin          0.0
NK Cells IL-2 rest               0.0
Two Way MLR 3 day                0.0
Two Way MLR 5 day                0.0
Two Way MLR 7 day                0.0
PBMC rest                        0.0
PBMC PWM                         0.0
PBMC PHA-L                       0.0
Ramos (B cell) none              0.0
Ramos (B cell) ionomycin         0.0
B lymphocytes PWM                0.0
B lymphocytes CD40L and IL-4     0.0
EOL-1 dbcAMP                     0.0
EOL-1 dbcAMP PMA/ionomycin       0.0
Dendritic cells none             0.0
Dendritic cells LPS              0.0
Dendritic cells anti-CD40        0.0
Monocytes rest                   0.0
Monocytes LPS                    0.0
Macrophages rest                 0.0
Macrophages LPS                  0.0
HUVEC none                       0.0
HUVEC starved                    0.0
HUVEC IL-1beta                   0.0
HUVEC IFN gamma                  0.0
HUVEC TNF alpha + IFN gamma      0.0
HUVEC TNF alpha + IL4            0.0
HUVEC IL-11                      0.0
Lung Microvascular EC none       0.0
Lung Microvascular EC TNFalpha + IL-1beta 0.0
Microvascular Dermal EC none     0.0
Microsvasular Dermal EC TNFalpha + IL-1beta 0.0
Bronchial epithelium TNFalpha + IL1beta 0.0
Small airway epithelium none     0.0
Small airway epithelium TNFalpha + IL-1beta 0.0
Coronery artery SMC rest         0.0
Coronery artery SMC TNFalpha + IL-1beta 0.0
Astrocytes rest                  2.8
Astrocytes TNFalpha + IL-1beta   2.8
KU-812 (Basophil) rest           0.0
KU-812 (Basophil) PMA/ionomycin  0.0
CCD1106 (Keratinocytes) none     0.0
CCD1106 (Keratinocytes) TNFalpha + IL-1beta 0.0
Liver cirrhosis                  0.0
NCI-H292 none                    0.0
NCI-H292 IL-4                    0.0
NCI-H292 IL-9                    0.0
NCI-H292 IL-13                   0.0
NCI-H292 IFN gamma               0.0
HPAEC none                       0.0
HPAEC TNF alpha + IL-1 beta      0.0
Lung fibroblast none             5.7
Lung fibroblast TNF alpha + IL-1 beta 0.0
Lung fibroblast IL-4             3.1
Lung fibroblast IL-9             2.3
Lung fibroblast IL-13            3.0
Lung fibroblast IFN gamma        0.0
Dermal fibroblast CCD1070 rest   0.0
Dermal fibroblast CCD1070 TNF alpha 0.0
Dermal fibroblast CCD1070 IL-1 beta 0.0
Dermal fibroblast IFN gamma      0.0
Dermal fibroblast IL-4           0.0
Dermal Fibroblasts rest          0.0
Neutrophils TNFa + LPS           0.0
Neutrophils rest                 0.0
Colon                            0.0
Lung                             2.8
Thymus                           100.0
Kidney                           0.0

[1013]

TABLE AJD
general oncology screening panel_v_2.4
                               Rel. Exp. (%)
                               Ag4135, Run
Tissue Name                    268390081
Colon cancer 1                 0.0
Colon cancer NAT 1             0.0
Colon cancer 2                 1.9
Colon cancer NAT 2             0.0
Colon cancer 3                 0.0
Colon cancer NAT 3             0.0
Colon malignant cancer 4       9.5
Colon normal adjacent tissue 4 0.0
Lung cancer 1                  0.0
Lung NAT 1                     0.0
Lung cancer 2                  16.2
Lung NAT 2                     0.0
Squamous cell carcinoma 3      0.0
Lung NAT 3                     0.0
metastatic melanoma 1          0.0
Melanoma 2                     0.0
Melanoma 3                     0.0
metastatic melanoma 4          17.9
metastatic melanoma 5          15.7
Bladder cancer 1               1.9
Bladder cancer NAT 1           0.0
Bladder cancer 2               0.0
Bladder cancer NAT 2           0.0
Bladder cancer NAT 3           0.0
Bladder cancer NAT 4           0.0
Prostate adenocarcinoma 1      100.0
Prostate adenocarcinoma 2      11.9
Prostate adenocarcinoma 3      1.8
Prostate adenocarcinoma 4      7.3
Prostate cancer NAT 5          8.4
Prostate adenocarcinoma 6      4.1
Prostate adenocarcinoma 7      6.6
Prostate adenocarcinoma 8      0.0
Prostate adenocarcinoma 9      56.3
Prostate cancer NAT 10         0.0
Kidney cancer 1                0.0
Kidney NAT 1                   4.7
Kidney cancer 2                0.0
Kidney NAT 2                   17.1
Kidney cancer 3                0.0
Kidney NAT 3                   1.7
Kidney cancer 4                0.0
Kidney NAT 4                   7.1

[1014] General_screening_panel_v1.4 Summary: Ag4135 Expression of this putative carboxypeptidase is highest in pancreas and bladder (CTs=20). Low but significant levels of expression are seen in adipose, testis, spleen, adult and fetal skeletal muscle, colon cancer tissue, fetal kidney, fetal liver, fetal lung, placenta, and a squamous cell carcinoma cell line. Therefore, therapeutic modulation of this gene may be useful in the treatment of diseases that affect these tissues including pancreatitis.

[1015] In addition, this gene is more highly expressed in fetal liver (CT=26) than in the adult counterpart (CT=40). Thus, expression of this gene may be used to differentiate between the fetal and adult source of this tissue. In addition, the relative overexpression of this gene in fetal tissue suggests that the protein product may enhance liver growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the carboxypeptidase encoded by this gene could be useful in treatment of liver related diseases.

[1016] Panel 4.1D Summary: Ag4135 This gene is expressed at significant levels only in the thymus (CT=33) in both runs. The protein encoded for by this gene could therefore play an important role in T cell development. Small molecule therapeutics, or antibody therapeutics designed against the carboxypeptidase encoded for by this gene could be utilized to modulate immune function (T cell development) and be important for organ transplant, AIDS treatment or post chemotherapy immune reconstitution.

[1017] general oncology screening panel_v—2.4 Summary: Ag4135 Expression of this gene is restricted to a sample derived from a prostate cancer (CT=32.6). Thus, expression of this gene could be used to differentiate between this sample and other samples on this panel and as a marker to detect the presence of prostate cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of prostate cancer.

Example D

[1018] Identification of Single Nucleotide Polymorphisms in NOVX Nucleic Acid Sequences

[1019] 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.

[1020] 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.

[1021] 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.

[1022] 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 (Alderbom et al., Determination of Single Nucleotide Polymorphisms by Real-time Pyrophosphate DNA Sequencing. Genome Research. 10 (8) 1249-1265, 2000).

[1023] 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.

TABLE SN1
PEPTIDYLPROLYL ISOMERASE A -like
Protein. CG142102-01 (NOV31a)
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13379649	521	G	A	154	Arg	His
13379648	560	T	C	167	Ile	Thr

[1024]

TABLE SN2
SA protein-like Protein CG59444-01 (NOV34a)
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13380147	338	G	A	65	Arg	Gln
13380148	891	A	T	249	Gly	Gly

[1025]

TABLE SN3
Potential phospholipid-transporting ATPase
VA -like Protein CG59361-01 (NOV33a)
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13377654	733	C	T	171	Arg	Cys
13380152	3845	T	C	1208	Leu	Pro
13380151	3884	C	T	1221	Ser	Leu

[1026]

TABLE SN4
MYOSIN 1G VALINE FORM-like
protein CG59522-02 (NOV36b)
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13380146	375	G	T	121	Ala	Ser

[1027]

TABLE SN5
Protein kinase D2 -like protein CG90879-01 (NOV38a).
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13380159	2189	G	T	717	Arg	Leu
13380158	2204	G	A	722	Gly	Asp

[1028]

TABLE SN6
Carboxypeptidase A1-like protein CG97955-03 (NOV42c).
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13380153	311	C	T	97	Leu	Leu
13380154	327	A	G	102	Glu	Gly

[1029]

TABLE SN7
Novel SNPs for HYDROLASE like-like
Protein CG107234-02 (NOV4b)
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13380137	150	A	G	46	Asn	Ser
13380139	448	C	A	145	Asn	Lys

[1030]

TABLE SN8
CtBP (D-isomer specific 2-hydroxyacid dehydrogenase)-like
protein CG113144-02 (NOV5a).
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13380136	8	A	G	0

[1031]

TABLE SN9
cGMF-stimulated 3′,5′-cyclic nucleotide phosphodiesterase-like
protein CG138130-01 (NOV13a).
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13380145	2667	A	G	846	Ala	Ala
13380144	2721	C	T	864	Tyr	Tyr

[1032]

TABLE SN10
MALEYLACETOACETATE ISOMERASE -like
protein CG138372-02 (NOV14a)
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13378194	111	G	A	32	Glu	Lys
13376309	141	G	A	42	Gly	Arg

[1033]

TABLE SN11
CHOLINE/ETHANOLAMINE KINASE-like
protein CG138563-01
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13380141	733	G	A	216	Glu	Lys

[1034]

TABLE SN12
Protein-tyrosine kinase ryk - Like -like protein CG138848-01
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13380138	1568	T	C	493	Leu	Ser

[1035]

TABLE SN13
Pyridoxal-dependent decarboxylase-like protein CG140041-01.
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13375791	1193	C	T	366	Arg	Trp
13375803	1285	G	A	396	Gln	Gln
13375802	1318	C	T	407	Ala	Ala

[1036]

TABLE SN14
ATP SYNTHASE B CHAIN, MITOCHONDRIAL-like
protein CG140612-02.
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13380164	858	T	C	0

[1037]

TABLE SN15
Dual specificity phosphatase -like protein CG140747-01.
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13379681	1502	C	T	482	Ser	Leu

[1038]

TABLE SN16
Human Stearoyl CoA Desaturase L-like protein CG105521-01.
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
cgsp:13380102	272	T	C	13	Ser	Pro
cgsp:13380103	463	C	A	76	Ile	Ile
cgsp:13379380	905	A	C	224	Leu	Met
hsnp:rs2958475	1104	C	T	290	Leu	Pro
hsnp:rs1054412	1232	A	G	333	Ala	Thr
cgsp:13380105	2466	G	A	UTR	N/A	N/A
cgsp:13380108	2974	T	C	UTR	N/A	N/A
cgsp:13380109	2981	T	C	UTR	N/A	N/A
cgsp:13380110	3046	T	G	UTR	N/A	N/A
cgsp:13380111	3153	T	C	UTR	N/A	N/A
cgsp:13380112	3338	G	A	UTR	N/A	N/A
cgsp:13380113	3441	T	C	UTR	N/A	N/A
cgsp:13380114	3646	G	A	UTR	N/A	N/A
cgsp:13380116	3791	A	G	UTR	N/A	N/A
cgsp:13380117	3856	C	T	UTR	N/A	N/A
cgsp:13380118	3869	A	C	UTR	N/A	N/A
cgsp:13380119	3915	T	A	UTR	N/A	N/A
cgsp:13380120	3943	A	G	UTR	N/A	N/A
cgsp:13380121	3963	T	C	UTR	N/A	N/A
cgsp:13380122	4023	A	G	UTR	N/A	N/A
cgsp:13380123	4033	T	C	UTR	N/A	N/A
cgsp:13380124	4042	A	G	UTR	N/A	N/A
cgsp:13380099	4061	G	A	UTR	N/A	N/A
cgsp:13380098	4073	G	A	UTR	N/A	N/A
cgsp:13380125	4103	G	A	UTR	N/A	N/A
cgsp:13380127	4174	A	G	UTR	N/A	N/A
cgsp:13380097	4229	G	A	UTR	N/A	N/A
cgsp:13380128	4309	A	T	UTR	N/A	N/A
cgsp:13380071	4574	C	A	UTR	N/A	N/A

[1039]

TABLE 17
Human aryl hydrocarbon receptor-like protein CG105355-01.
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
1	757	A	G	48	Asp	Gly
2	869	T	C	85	Val	Val
3	1132	A	G	173	Gln	Arg
4	2028	G	A	472	Ala	Thr
5	2275	G	A	554	Arg	Lys

Example E

[1040] Method of Use for NOVX-Related Polypeptides and Polynucleotides

[1041] The present invention is partially based on the identification of biological macromolecules differentially modulated in a pathologic state, disease, or an abnormal condition or state, and/or based on novel associations of proteins and polypeptides and the nucleic acids that encode them, as identified in a yeast 2-hybrid screen using a cDNA library or one-by-one matrix reactions. Among the pathologies or diseases of present interest include metabolic diseases including those related to endocrinologic disorders, cancers, various tumors and neoplasias, inflammatory disorders, central nervous system disorders, and similar abnormal conditions or states. Important metabolic disorders with which the biological macromolecules are associated include obesity and diabetes mellitus, especially obesity and Type II diabetes. It is believed that obesity predisposes a subject to Type II diabetes. In very significant embodiments of the present invention, the biological macromolecules implicated in these pathologies and conditions are proteins and polypeptides, and in such cases the present invention is related as well to the nucleic acids that encode them. Methods that may be employed to identify relevant biological macromolecules include any procedures that detect differential expression of nucleic acids encoding proteins and polypeptides associated with the disorder, as well as procedures that detect the respective proteins and polypeptides themselves. Significant methods that have been employed by the present inventors, include GeneCalling® technology and SeqCalling™ technology, disclosed respectively, in U.S. Pat. No. 5,871,697, and in U.S. Ser. No. 09/417,386, filed Oct. 13, 1999, each of which is incorporated herein by reference in its entirety. GeneCalling® is also described in Shimkets, et al., Nature Biotechnology 17:198-803 (1999).

[1042] The invention provides polypeptides and nucleotides encoded thereby that have been identified as having novel associations with a disease or pathology, or an abnormal state or condition, in a mammal. Included in the invention are nucleic acid sequences and their encoded polypeptides. The sequences are collectively referred to as “obesity and/or diabetes nucleic acids” or “obesity and/or diabetes polynucleotides” and the corresponding encoded polypeptide is referred to as an “obesity and/or diabetes polypeptide” or “obesity and/or diabetes protein”. For example, an obesity and/or diabetes nucleic acid according to the invention is a nucleic acid including an obesity and/or diabetes nucleic acid, and an obesity and/or diabetes polypeptide according to the invention is a polypeptide that includes the amino acid sequence of an obesity and/or diabetes polypeptide. Unless indicated otherwise, “obesity and/or diabetes” is meant to refer to any of the sequences having novel associations disclosed herein.

[1043] The present invention identifies a set of proteins and polypeptides, including naturally occurring polypeptides, precursor forms or proproteins, or mature forms of the polypeptides or proteins, which are implicated as targets for therapeutic agents in the treatment of various diseases, pathologies, abnormal states and conditions. A target may be employed in any of a variety of screening methodologies in order to identify candidate therapeutic agents which interact with the target and in so doing exert a desired or favorable effect. The candidate therapeutic agent is identified by screening a large collection of substances or compounds in an important embodiment of the invention. Such a collection may comprise a combinatorial library of substances or compounds in which, in at least one subset of substances or compounds, the individual members are related to each other by simple structural variations based on a particular canonical or basic chemical structure. The variations may include, by way of nonlimiting example, changes in length or identity of a basic framework of bonded atoms; changes in number, composition and disposition of ringed structures, bridge structures, alicyclic rings, and aromatic rings; and changes in pendent or substituents atoms or groups that are bonded at particular positions to the basic framework of bonded atoms or to the ringed structures, the bridge structures, the alicyclic structures, or the aromatic structures.

[1044] A polypeptide or protein described herein, and that serves as a target in the screening procedure, includes the product of a naturally occurring polypeptide or precursor form or proprotein. The naturally occurring polypeptide, precursor or proprotein includes, e.g., the full-length gene product, encoded by the corresponding gene. The naturally occurring polypeptide also includes the polypeptide, precursor or proprotein encoded by an open reading frame described herein. A “mature” form of a polypeptide or protein arises as a result of one or more naturally occurring processing steps as they may occur within the cell, including a host cell. The processing steps occur as the gene product arises, e.g., via cleavage of the amino-terminal methionine residue encoded by the initiation codon of an open reading frame, or the proteolytic cleavage of a signal peptide or leader sequence. Thus, a mature form arising from a precursor polypeptide or protein that has residues 1 to N, where residue 1 is the N-terminal methionine, would have residues 2 through N remaining. Alternatively, a mature form arising from a precursor polypeptide or protein having residues 1 to N, in which an amino-terminal signal sequence from residue 1 to residue M is cleaved, includes the residues from residue M+1 to residue N remaining. A “mature” form of a polypeptide or protein may also arise from non-proteolytic post-translational modification. Such non-proteolytic processes include, e.g., glycosylation, myristylation or phosphorylation. In general, a mature polypeptide or protein may result from the operation of only one of these processes, or the combination of any of them.

[1045] As used herein, “identical” residues correspond to those residues in a comparison between two sequences where the equivalent nucleotide base or amino acid residue in an alignment of two sequences is the same residue. Residues are alternatively described as “similar” or “positive” when the comparisons between two sequences in an alignment show that residues in an equivalent position in a comparison are either the same amino acid or a conserved amino acid as defined below.

[1046] As used herein, a “chemical composition” relates to a composition including at least one compound that is either synthesized or extracted from a natural source. A chemical compound may be the product of a defined synthetic procedure. Such a synthesized compound is understood herein to have defined properties in terms of molecular formula, molecular structure relating the association of bonded atoms to each other, physical properties such as electropherographic or spectroscopic characterizations, and the like. A compound extracted from a natural source is advantageously analyzed by chemical and physical methods in order to provide a representation of its defined properties, including its molecular formula, molecular structure relating the association of bonded atoms to each other, physical properties such as electropherographic or spectroscopic characterizations, and the like.

[1047] As used herein, a “candidate therapeutic agent” is a chemical compound that includes at least one substance shown to bind to a target biopolymer. In important embodiments of the invention, the target biopolymer is a protein or polypeptide, a nucleic acid, a polysaccharide or proteoglycan, or a lipid such as a complex lipid. The method of identifying compounds that bind to the target effectively eliminates compounds with little or no binding affinity, thereby increasing the potential that the identified chemical compound may have beneficial therapeutic applications. In cases where the “candidate therapeutic agent” is a mixture of more than one chemical compound, subsequent screening procedures may be carried out to identify the particular substance in the mixture that is the binding compound, and that is to be identified as a candidate therapeutic agent.

[1048] As used herein, a “pharmaceutical agent” is provided by screening a candidate therapeutic agent using models for a disease state or pathology in order to identify a candidate exerting a desired or beneficial therapeutic effect with relation to the disease or pathology. Such a candidate that successfully provides such an effect is termed a pharmaceutical agent herein. Nonlimiting examples of model systems that may be used in such screens include particular cell lines, cultured cells, tissue preparations, whole tissues, organ preparations, intact organs, and nonhuman mammals. Screens employing at least one system, and preferably more than one system, may be employed in order to identify a pharmaceutical agent. Any pharmaceutical agent so identified may be pursued in further investigation using human subjects.

[1049] A. NOV 41: Human Cytosolic HMG CoA Synthase-Like Proteins

[1050] The following sections describe the study design(s) and the techniques used to identify the Cytosolic HMG CoA synthase—encoded NOV41 protein, and any variants thereof, as being suitable as diagnostic markers, targets for an antibody therapeutic and targets for a small molecule drugs for obesity and/or diabetes.

[1051] A large number of mouse strains have been identified that differ in body mass and composition. The AKR and NZB strains are obese, the SWR, C57L and C57BL/6 strains are of average weight whereas the SM/J and Cast/Ei strains are lean. Understanding the gene expression differences in the major metabolic tissues from these strains will elucidate the pathophysiologic basis for obesity. These specific strains of rat were chosen for differential gene expression analysis because quantitative trait loci (QTL) for body weight and related traits had been reported in published genetic studies. Tissues included whole brain, skeletal muscle, visceral adipose, and liver.

[1052] Cytoplasmic HMG CoA synthase mediates an early step in cholesterol biosynthesis. This enzyme condenses acetyl-CoA with acetoacetyl-CoA to form HMG-CoA, which is the substrate for HMG-CoA Reductase. See generally, Carlsson et al., 2001 Am J Physiol Endocrinol Metab. 281(4):E772-81; Lopez et al., 2001 Mol Cell Biochem. 217(1-2):57-66; Olivier et al., 2000 Biochim Biophys Acta. 1529(1-3):89-102; Mascaro et al., 2000 Biochem J. 350 Pt 3:785-90; Sato et al., 2000 J Biol Chem. 275(17):12497-502; Mascaro et al., 2000 Arch Biochem Biophys. 374(2):286-92; Scharnagl et al., 1995 J Lipid Res. 36(3):622-7; and Royo et al., 1993 Biochem J. 289 (Pt 2):557-60.

[1053] NOV41 Expression

[1054] A gene fragment of the mouse cytosolic HMG CoA synthase was initially found to be up-regulated by 7 fold in the liver of the NZB mouse relative to the SMJ mouse strain using CuraGen's GeneCalling™ method of differential gene expression. A differentially expressed mouse gene fragment migrating, at approximately 312.1 nucleotides in length (FIGS. 1A and 1B.—vertical line) was definitively identified as a component of the mouse Cytosolic HMG CoA synthase cDNA (in the graphs, the abscissa is measured in lengths of nucleotides and the ordinate is measured as signal response). The method of competitive PCR was used for conformation of the gene assessment. The chromatographic peaks corresponding to the gene fragment of the rat Cytosolic HMG CoA synthase are ablated when a gene-specific primer (see below) competes with primers in the linker-adaptors during the PCR amplification. The peaks at 312.1 nt in length are ablated in the sample from both the NZB and SMJ mice. The direct sequence of the 312 nucleotide-long gene fragment and the gene-specific primers used for competitive PC are indicated in italic. The gene-specific primers at the 5′ and 3′ ends of the fragment are in bold. This result was confirmed by competitive PCR.

[1055] Biochemistry

[1056] Cytosolic HMG CoA synthase condenses acetyl-CoA with acetoacetyl-CoA to form HMG-CoA, which is the substrate for HMG-CoA Reductase. This condensation reaction occurs above the diversion point to farnesoic acid in the cholesterol biosynthetic pathway.

[1057] The reaction proceeds as follows:

acetyl-CoA+H2O+acetoacetyl-CoA=(S)-3-hydroxy-3-methylglutaryl-CoA+CoA

[1058] Rationale for use as a Diagnostic and/or Target for Small Molecule Drugs and Antibody Therapeutics

[1059] HMG CoA synthase is up-regulated 7-fold in a genetic model of obesity characterized by apparent LXRα activation (adipose induction of ApoE, malic enzyme, ATP citrate lyase, FAS, SCD), thus HMG CoA synthase provides the substrate for LXRa ligands.

[1060] Inhibition of this enzyme may be a treatment for the prevention or treatment of obesity.

[1061] Taken in total, the data indicates that an inhibitor of the human Cytosolic HMG CoA synthase enzyme would be beneficial in the treatment of obesity and/or diabetes.

[1062] B. NOV 3: Human Stearoyl CoA Desaturase—Like Proteins

[1063] The following sections describe the study design(s) and the techniques used to identify the stearoyl CoA desaturase—encoded NOV3 protein, and any variants thereof, as being suitable as diagnostic markers, targets for an antibody therapeutic and targets for a small molecule drugs for obesity and/or diabetes.

[1064] Stearoyl CoA desaturase (SCD) utilizes O2 and electrons from reduced cytochrome b5 to catalyze the insertion of a double bond into a spectrum of fatty acyl-CoA substrates, including palmitoyl-CoA and stearoyl-CoA at the position of the 9th carbon (“delta-9 desaturase”). Stearoyl CoA desaturase expression is regulated by both SREBP and C/EBPalpha, transcription factors that are essential in adipose differentiation and lipogenesis. SCD is a key enzyme in the synthesis of unsaturated fatty acids that are being stored as triglycerides (TG), and the induction of TG synthesis is highly dependent on the expression of SCD. Recently it was shown that mice lacking SCD1 are lean and hypermetabolic, while ob/ob mice with a mutation in SCD1 are less obese then regular ob/ob mice, indicating that SCD1 is an important component in the metabolic actions of leptin. While in rodents there are two SCD genes, SCD1 and SCD2, there is only one SCD gene in human.

[1065] SCD2 is up-regulated in two genetic models of obesity. In adipose tissue of the obese NZB/BINJ mice, SCD2 was up-regulated compared to the lean SM/J mice. In visceral adipose from the Spontaneous Hypertensive Rats (SHR), SCD2 was also up-regulated when compared to subcutaneous adipose from the same strain. Moreover, our data from the diet-induced obesity model showed that for all 4 standard deviations of obese mice (SD1, SD4, SD7 and hyperglycemic SD7) on a high fat diet, SCD1 was down-regulated in brown adipose. In white adipose, SCD1 was up-regulated in the moderately obese SD1 mice, while it was down-regulated in white adipose of severely obese mice (SD7). This suggests that down-regulation of SCD is a compensatory mechanism in response to the high fat diet, which manifests itself earlier in brown adipose and thus, may be protective. Therefore, an antagonist for SCD to inhibit SCD directly may be an effective therapeutic for obesity.

[1066] The spontaneously hypertensive rat (SHR) is a strain exhibiting features of the human Metabolic Syndrome X. The phenotypic features include obesity, hyperglycemia, hypertension, dyslipidemia and dysfibrinolysis. Tissues were removed from adult male rats and a control strain (Wistar—Kyoto) to identify the gene expression differences that underlie the pathologic state in the SHR and in animals treated with various anti-hyperglycemic agents such as troglitizone. Tissues included sub-cutaneous adipose, visceral adipose and liver.

[1067] A large number of mouse strains have been identified that differ in body mass and composition. The AKR and NZB strains are obese, the SWR, C57L and C57BL/6 strains are of average weight whereas the SM/J and Cast/Ei strains are lean. Understanding the gene expression differences in the major metabolic tissues from these strains will elucidate the pathophysiologic basis for obesity. These specific strains of rat were chosen for differential gene expression analysis because quantitative trait loci (QTL) for body weight and related traits had been reported in published genetic studies. Tissues included whole brain, skeletal muscle, visceral adipose, and liver.

[1068] Bone marrow-derived human mesenchymal stem cells have the capacity to differentiate into muscle, adipose, cartilage and bone. Culture conditions have been established that permit the differentiation in vitro along the pathway to adipose, cartilage and bone. Understanding the gene expression changes that accompany these distinct differentiation processes would be of considerable biologic value. Regulation of adipocyte differentiation would have importance in the treatment of obesity, diabetes and hypertension. Human mesenchymal stem cells from 3 donors were obtained and differentiated in vitro according to published methods. RNA from samples of the undifferentiated, mid-way differentiated and fully differentiated cells was isolated for analysis of differential gene expression. See generally, Miyazaki et al., 2001 J Lipid Res. 42(7):1018-24; Kim et al. 2000 J Lipid Res. 41(8):1310-6; Kim et al. 1998 Cell. 93(5):693-704; Miyazaki et al. 2000 J Biol Chem. 275(39):30132-8; Kim et al. 1999 Biochem Biophys Res Commun. 266(1):1-4; Miyazaki et al. 2001 J Biol Chem. 276(42):39455-61; Bene et al. 2001 Biochem Biophys Res Commun 284(5):1194-8; and Cohen et al. 2002 Science 297(5579):240-3.

[1069] The predominant cause for obesity in clinical populations is excess caloric intake. This so-called diet-induced obesity (DIO) is mimicked in animal models by feeding high fat diets of greater than 40% fat content. The DIO study was established to identify the gene expression changes contributing to the development and progression of diet-induced obesity. In addition, the study design seeks to identify the factors that lead to the ability of certain individuals to resist the effects of a high fat diet and thereby prevent obesity. The sample groups for the study had body weights+1 S.D., +4 S.D. and +7 S.D. of the chow-fed controls (See Table E1). In addition, the biochemical profile of the +7 S.D. mice revealed a further stratification of these animals into mice that retained a normal glycemic profile in spite of obesity and mice that demonstrated hyperglycemia. Tissues examined included hypothalamus, brainstem, liver, retroperitoneal white adipose tissue (WAT), epididymal WAT, brown adipose tissue (BAT), gastrocnemius muscle (fast twitch skeletal muscle) and soleus muscle (slow twitch skeletal muscle). The differential gene expression profiles for these tissues should reveal genes and pathways that can be used as therapeutic targets for obesity.

[1070] NOV3 Expression

[1071] A fragment of the rat Stearoyl CoA Desaturase 2 gene was initially found to be up-regulated by 1.9 fold in the visceral adipose relative to subcutaneous adipose of the Spntaneous Hypertensive rats (SHR) using CuraGen's GeneCalling™ method of differential gene expression. A differentially expressed rat gene fragment migrating, at approximately 373.6 nucleotides in length was definitively identified as a component of the rat Stearoyl CoA Desaturase 2 cDNA. The method of comparative PCR was used for conformation of the gene assessment. The electropherographic peaks corresponding to the gene fragment of the rat Stearoyl CoA Desaturase 2 are ablated when a gene-specific primer competes with primers in the linker-adaptors during the PCR amplification. The peaks at 373.6 nt in length are ablated in the sample from both the visceral and subcutaneous adipose. The difference in gene expression in SHR visceral vs subcutaneous adipose is +1.9 fold.

[1072] A gene fragment of mouse Stearoyl CoA Desaturase 2 was also found to be up-regulated by 1.9 fold in the adipose tissue of NZB/BINJ obese mice relative to SM/J lean mice using CuraGen's GeneCalling™ method of differential gene expression. A differentially expressed mouse gene fragment migrating, at approximately 94 nucleotides in length was definitively identified as a component of the mouse Stearoyl CoA Desaturase 2 cDNA. The method of comparative PCR was used for conformation of the gene assessment. The electropherographic peaks corresponding to the gene fragment of mouse Stearoyl CoA Desaturase 2 are ablated when a gene-specific primer competes with primers in the linker-adaptors during the PCR amplification. The peaks at 94 nt in length are ablated in the sample from both the NZB/BINJ obese and SM/J lean mice. The difference in gene expression in B/BINJ (obese) vs SM'J (lean) adipose is +1.9 fold.

[1073] A gene fragment of human Stearoyl CoA Desaturase was also found to be up-regulated by 2-4 fold in differentiated adipocytes relative to midway differentiated adipocytes using CuraGen's GeneCalling™ method of differential gene expression. A differentially expressed human gene fragment migrating, at approximately 443 nucleotides in length was definitively identified as a component of the human Stearoyl CoA Desaturase cDNA. The method of comparative PCR was used for conformation of the gene assessment. The electropherographic peak corresponding to the gene fragment of human Stearoyl CoA Desaturase is ablated when a gene-specific primer competes with primers in the linker-adaptors during the PCR amplification. The peak at 443 nt in length is ablated in the sample from the fully differentiated adipocytes from donor 2. The difference in gene expression in differentiated adipocytes vs midway differentiated adipocytes is +3.9 fold.

[1074] A gene fragment of mouse Stearoyl CoA Desaturase 1 was also found to be down-regulated by 2 fold in brown adipose tissue of obese hyperinsulinemic ngsd7 mice relative to normal weight (chow-fed) mice using CuraGen's GeneCalling™ method of differential gene expression. A differentially expressed mouse gene fragment migrating, at approximately 94 nucleotides in length was definitively identified as a component of the mouse Stearoyl CoA Desaturase 1 cDNA. The method of comparative PCR was used for conformation of the gene assessment. The electropherographic peaks corresponding to the gene fragment of mouse Stearoyl CoA Desaturase 1 are ablated when a gene-specific primer competes with primers in the linker-adaptors during the PCR amplification. The peak at 94 nt in length is ablated in the sample from the obese hyperinsulinemic ngsd7 mice. The difference in gene expression in sd7-brown adipose vs chow-brown adipose is −2 fold.

[1075] Summary of GeneCalling Results: Up-regulation of stearoyl CoA desaturase is associated with obesity in 2 genetic models of rodent obesity, a diet-induced obesity model, and adipose differentiation.

[1076] Biochemistry

[1077] Stearoyl CoA desaturase (also known as Delta-9 desaturase) utilizes O2 and electrons from reduced cytochrome b5 to catalyze the insertion of a double bond into a spectrum of fatty acyl-CoA substrates, including palmitoyl-CoA and stearoyl-CoA. Iron acts as a cofactor for the reaction:

Stearoyl-CoA+NADPH+O2→Oleoyl-CoA+NADP++2 H20

[1078] Pathways Relevant to the Etiology and Pathogenesis of Obesity and/or Diabetes

[1079] PathCalling screening identified an interaction between SCD and CREB3, a poorly characterized general transcriptional factor. It has been shown in the literature that CREB3 interacts with a cytosolic protein known as HCFC1 (host cell factor C1). This interaction prevents nuclear translocation of CREB3, thus interfering with its transcriptional activity. Similar to HCFC1, SCD may inhibit CREB3 functions by trapping this transcriptional factor in cytoplasm. The significance of this interaction remains to be elucidated.

[1080] Rationale for Use of the Human Stearoyl CoA Desaturase Gene as a Diagnostic and/or Target for Small Molecule Drugs and Antibody Therapeutics

[1081] The following is a summary of the findings from the discovery studies, supplementary investigations and assays that also incorporates knowledge in the scientific literature. Taken in total, the data indicates that an inhibitor/antagonist of the human Stearoyl CoA Desaturase would be beneficial in the treatment of obesity and/or diabetes.

[1082] Stearoyl CoA desaturase (SCD) is a key enzyme in the synthesis of unsaturated fatty acids that are being stored as triglyceride molecules and induction of triglyceride synthesis is highly dependent on SCD expression. In our GeneCalling studies, we have found that SCD2 is upregulated in “bad” (i.e. visceral and obese) fat. In addition, SCD1 is upregulated in white adipose of moderately obese mice, whereas it is downregulated in white adipose of extremely obese mice. Furthermore, expression of the SCD gene is downregulated in all stages of obesity in brown adipose tissue, known for a higher level of energy utilization versus storage. This suggests that down-regulation of SCD is a compensatory mechanism in response to a high fat diet, which manifests itself earlier in brown adipose and thus, may be protective.

[1083] Mice deficient in SCD1 have very low levels of triglyceride synthesis in the liver, which is reflected in low levels of triglycerides in the VLDL and LDL lipoprotein fractions (Miyazaki et al., 2000; Miyazaki et al., 2001). There are other reports of SCD1 deficient mice that are leaner and have hypermetabolism (Cohen et al., 2002). In addition, transcription of the SCD gene is regulated by SREBP as well as C/EBPalpha, transcription factors that have been shown to be essential in adipose differentiation and lipogenesis (Bene et al., 2001). Moreover, antidiabetic thiazolidinediones downregulate SCD1 in cultured primary adipocytes (Kim et al., 2000). Taken together, these findings suggest that an antagonist for SCD to inhibit SCD directly may be an effective therapeutic for obesity.

[1084] C. NOV2: Human Aryl Hydrocarbon Receptor—Like Proteins

[1085] The following sections describe the study design(s) and the techniques used to identify the human Aryl Hydrocarbon Receptor—encoded NOV2 protein, and any variants thereof, as being suitable as diagnostic markers, targets for an antibody therapeutic and targets for a small molecule drugs for obesity and/or diabetes.

[1086] The Aryl Hydrocarbon Receptor (AHR) is a ligand-dependent transcription factor. 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) is a known activating ligand that initiates expression of multiple genes, including CYP1B1 and glutathione S-transferase. The Aryl Hydrocarbon Receptor forms a heterodimer with ARNT, a nuclear translocator, to form an active complex that crosses the nuclear membrane and binds to DNA. As a result of activation of ABR, PPAR-γ can become suppressed and GLUT4 expression becomes down regulated in adipose tissue. These actions are of biological importance in the development of insulin resistance and of diabetes.

[1087] The Aryl Hydrocarbon Receptor is a member of the PAS (Per-Ahr-Sim) superfamily of transcription factors having functions in development and detoxification. Only recently has any member of this family been associated with obesity and diabetes.

[1088] Gestational diabetes complicates 4% of pregnancies and is a prognostic factor in the development of Type II diabetes. In addition, offspring of women who develop gestational diabetes are at increased risk of becoming obese and developing diabetes. Thus, the differences in gene expression from the metabolic tissues of gestational diabetics and non-diabetic should reveal underlying differences related to the pathophysiology of diabetes. Because many women deliver by C-section this patient population provides an opportunity to examine gene expression changes in surgical material from normals, gestational diabetics treated by diet alone and gestational diabetics treated with insulin. These patients, generally, do not suffer from confounding medical conditions and are not exposed to drugs that may influence gene expression. In this IRB-approved study, clinical information and samples were obtained from sub-cutaneous adipose, skeletal muscle, visceral adipose (omentum) and smooth muscle (uterus) from women giving birth by non-emergency C-section. Maternal and cord blood were also obtained for genotype analysis. The body mass index spanned a wide range in this patient population. Those patients meeting the diagnostic criteria for gestational diabetes were treated with either dietary modification and/or insulin therapy.

[1089] See generally, Ma 2001 Curr Drug Metab.: 149-64; Safe 2001 Toxicol Lett. 120(1-3):1-7; Ema 2001 Seikagaku. 73(2):81-8; Delescluse et al. 2000 Toxicology. 153(1-3):73-82; Gu et al 2000 Annu Rev Pharmacol Toxicol. 40:519-61; Schwarz et al. 2000 Toxicol Lett. 112-113:69-77; Okino et al. 2000 Vitam Horm. 59:241-64; Crews et al. 1999 Curr Opin Genet Dev. 9(5):580-7; Safe et al. 1998 Toxicol Lett. 102-103:343-7; Gonzalez et al. 1998 Drug Metab Dispos. 26(12):1194-8; Lahvis et al., 1998 Biochem Pharmacol. 56(7):781-7; Holder et al. 2000 Hum Mol Genet. 9(1):101-8; Seidel et al, 2000 Toxicol.Sci. 55 :107-115 ; and Allen et al. 2001 Drug Metab.Dispos. 29:1074-1079.

[1090] The predominant cause for obesity in clinical populations is excess caloric intake. This so-called diet-induced obesity (DIO) is mimicked in animal models by feeding high fat diets of greater than 40% fat content. The DIO study was established to identify the gene expression changes contributing to the development and progression of diet-induced obesity. In addition, the study design seeks to identify the factors that lead to the ability of certain individuals to resist the effects of a high fat diet and thereby prevent obesity. The sample groups for the study had body weights +1 S.D., +4 S.D. and +7 S.D. of the chow-fed controls (below). In addition, the biochemical profile of the +7 S.D. mice revealed a further stratification of these animals into mice that retained a normal glycemic profile in spite of obesity and mice that demonstrated hyperglycemia. Tissues examined included hypothalamus, brainstem, liver, retroperitoneal white adipose tissue (WAT), epididymal WAT, brown adipose tissue (BAT), gastrocnemius muscle (fast twitch skeletal muscle) and soleus muscle (slow twitch skeletal muscle). The differential gene expression profiles for these tissues should reveal genes and pathways that can be used as therapeutic targets for obesity.

[1091] A gene fragment of the human Aryl Hydrocarbon Receptor was initially found to be up-regulated by 1.9 fold in the adipose tissues of human gestational diabetics relative to normal pregnant females using CuraGen's GeneCalling™ method of differential gene expression. A differentially expressed human gene fragment migrating, at approximately 131 nucleotides in length was definitively identified as a component of the human Aryl Hydrocarbon Receptor cDNA. The method of competitive PCR was used for conformation of the gene assessment. The chromatographic peaks corresponding to the gene fragment of the human Aryl Hydrocarbon Receptor are ablated when a gene-specific primer competes with primers in the linker-adaptors during the PCR amplification. The peaks at 131 nt in length are ablated in the sample from both the gestational diabetics and normal patients.

[1092] Additionally, gene fragments corresponding to the mouse orthologue of AHR and two AHR-binding proteins, ARNT (AHR nuclear transporter) and AIP (AHR interacting protein) were found to have altered expression in a mouse model of dietary-induced obesity. The altered expression of these genes in the animal model support the role of the Aryl Hydrocarbon Receptor in the pathogenesis of obesity and/or diabetes.

[1093] Pathways Relevant to Obesity and/or Diabetes

[1094] Alterations in expression of the human Aryl Hydrocarbon Receptor and associated gene products function in the etiology and pathogenesis of obesity and/or diabetes, based on the unique findings of these discovery studies in conjunction with what has been reported in the literature. The outcome of inhibiting the action of the human Aryl Hydrocarbon Receptor would be a reduction of Insulin Resistance, a major problem in obesity and/or diabetes.

[1095] In gestational diabetes, a polymeric complex comprising aryl hydrocarbon receptor, a heat shock protein (HSP) such as HSP90 and AHR-interacting protein (AIP) is upregulated. The aryl hydrocarbon receptor and AIP are translocated to the nucleus and interact with ARNT. This complex causes increased gene expression of factors that inhibit GLUT 4 and PPARγ, resulting in insulin resistance.

[1096] Rationale for use as a Diagnostic and/or Target for Small Molecule Drugs and Antibody Therapeutics

[1097] The following is a summary of the findings from the discovery studies, supplementary investigations and assays that also incorporates knowledge in the scientific literature. Taken in total, the data indicates that an inhibitor/antagonist of the human Aryl Hydrocarbon Receptor would be beneficial in the treatment of obesity and/or diabetes:

[1098] a) Aryl Hydrocarbon was upregulated 1.9 fold in sub-cutaneous adipose from gestational diabetics. TCDD, an AHR agonist, suppresses PPAR-γ. Conversely TZDs activate PPAR-γ.

[1099] b) AHR activation decreases GLUT4 expression in adipose.

[1100] c) The clinical rise may represent a compensatory response.

[1101] d) No dysregulation of toxification genes (CYP1A1, CYP1A2, or CYP1B).

[1102] e) Upregulated in obese, hyperglycemic mouse liver and adipose. AHR nuclear translocator (ARNT) and AHR interacting protein (AIP) are also upregulated.

Example F

[1103] NOV35b (CG59482-02 Alignment with Trypsinogen

[1104] Table F1 shows a ClustW alignment of the CG59482-02 splice variant with trypsinogen (TRY1_HUMAN). The signal sequence extends from 1-15 and the propeptide sequence extends from 16-23 of SEQ ID NO: 341 (indicated by arrows). These two sequence fragments would normally be cleaved away from the mature protein. The residues in which form the catalytic triad are indicate by a “#” beneath the sequence.

[1105] Crystalographic data is also presented.

[1106] FIG. 1 shows the x-ray crystal structure of trypsin 1 at a 2.2 Å resolution (Gaboriaud, C. et. al, Jol. Mol. Biol., 1996, 259:995-1010)(PDB code 1TRN). The sequences absent in the CG59482-02 splice variant are indicated by small arrows. The view in FIG. 1 shows the active site facing outward with a diisopropyl-phosphofluoridate inhibitor in the active site (indicated by large arrows).

[1107] FIG. 2 shows the three residues which form the catalytic triad of the active site (indicated by arrowheads).

[1108] The mechanism for catalytic triad formation is shown in FIG. 3. The pKa for the serine hydroxyl is usually about 13, which makes it a poor nucleophile. The aspartate, histidine and serine are arranged in a charge relay system of hydrogen bonds which helps to lower this pKa which makes the sidechain more reactive. The carboxyl side chain on aspartate attracts a proton from histidine, which in turn, abstracts a proton from the hydroxyl of serine allowing it to react with and then cleave the polypeptide substrate.

[1109] Since the CG59482-02 splice variant is missing the Asp107 and His63, the resulting protein cannot form a catalytic triad and therefore would be enzymatically inactive. It is unclear from this stucture what effects the sequence deletion would have upon substrate binding since a small protease inhibitor is shown in the binding site. However, in one embodiment a polypeptide is much larger and has specific interactions with the deleted portions of CG59482-02 (assuming that the protein folded into a similar structure).

Other Embodiments

[1110] Although particular embodiments have been disclosed herein in detail, this has been done by way of example for purposes of illustration only, and is not intended to be limiting with respect to the scope of the appended claims, which follow. In particular, it is contemplated by the inventors that various substitutions, alterations, and modifications may be made to the invention without departing from the spirit and scope of the invention as defined by the claims. The choice of nucleic acid starting material, clone of interest, or library type is believed to be a matter of routine for a person of ordinary skill in the art with knowledge of the embodiments described herein. Other aspects, advantages, and modifications considered to be within the scope of the following claims. The claims presented are representative of the inventions disclosed herein. Other, unclaimed inventions are also contemplated. Applicants reserve the right to pursue such inventions in later claims.

Claims

1. An isolated polypeptide comprising 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 110.

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 110.

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 110.

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 110.

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 110 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 110.

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 110.

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 110.

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 110.

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 110, 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 110.

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 110.

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.