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 124, or polypeptide sequences, which represents the group consisting of SEQ ID NO: 2n, wherein n is an integer between 1 and 124.

[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 124, 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.

DETAILED DESCRIPTION OF THE INVENTION

[0023] The present invention provides novel nucleotides and polypeptides encoded thereby. Included in the invention are the novel nucleic acid sequences, their encoded polypeptides, antibodies, and other related compounds. The sequences are collectively referred to herein as “NOVX nucleic acids” or “NOVX polynucleotides” and the corresponding encoded polypeptides are referred to as “NOVX polypeptides” or “NOVX proteins.” Unless indicated otherwise, “NOVX” is meant to refer to any of the novel sequences disclosed herein. Table A provides a summary of the NOVX nucleic acids and their encoded polypeptides.

TABLE A
Sequences and Corresponding SEQ ID Numbers
		SEQ ID	SEQ ID
		NO	NO
NOVX	Internal	(nucleic	(amino
Assignment	Identification	acid)	acid)	Homology
1a	CG106764-01	1	2	Citron Kinase
1b	268667493	3	4	RHO/RAC-Interacting Citron Kinase
1c	268667539	5	6	RHO/RAC-Interacting Citron Kinase
1d	268667543	7	8	RHO/RAC-Interacting Citron Kinase
1e	268667555	9	10	RHO/RAC-Interacting Citron Kinase
1f	268667574	11	12	RHO/RAC-Interacting Citron Kinase
1g	CG106764-02	13	14	RHO/RAC-Interacting Citron Kinase
2a	CG117662-01	15	16	Renal Renin Precursor
2b	CG117662-02	17	18	Renal Renin Precursor
3a	CG118051-03	19	20	Aldehyde Dehydrogenase
3b	CG118051-02	21	22	Aldehyde Dehydrogenase
3c	CG118051-03	23	24	Aldehyde Dehydrogenase
4a	CG120277-01	25	26	Aldehyde Dehydrogenase-3
4b	CG120277-02	27	28	Aldehyde Dehydrogenase-3
5a	CG140468-01	29	30	Serine/Threonine-Protein Kinase PAK 1
5b	CG140468-02	31	32	Serine/Threonine-Protein Kinase PAK 1
6a	CG142182-01	33	34	Ubiquitin Carboxyl-terminal Hydrolase
				15
7a	CG142564-01	35	36	Carnitine O-Palmitoyltransferase I
8a	CG142797-01	37	38	Cathepsin L
9a	CG143216-01	39	40	Laminin Gamma 3 Chain Precursor
10a	CG143787-01	41	42	Disintegrin Protease
10b	278889162	43	44	Disintegrin Protease
10c	278689868	45	46	Disintegrin Protease
11a	CG144112-01	47	48	NEUROPSIN PRECURSOR like homo
				sapiens
11b	CG144112-04	49	50	Neuropsin Precursor
11c	255501898	51	52	Neuropsin Precursor
11d	255612524	53	54	Neuropsin Precursor
11e	255612566	55	56	Neuropsin Precursor
11f	306434072	57	58	Neuropsin Precursor
11g	CG144112-02	59	60	Neuropsin Precursor
11h	CG144112-03	61	62	Neuropsin Precursor
12a	CG144497-01	63	64	Adenylosuccinate Synthetase Muscle
				Isozyme
13a	CG144686-01	65	66	Mast Cell Carboxypeptidase A Precursor
13b	278690008	67	68	Mast Cell Carboxypeptidase A Precursor
13c	278690035	69	70	Mast Cell Carboxypeptidase A Precursor
13d	CG144686-02	71	72	Mast Cell Carboxypeptidase A Precursor
14a	CG144906-01	73	74	Testisin Precursor
14b	CG144906-02	75	76	Testisin Precursor
15a	CG144997-01	77	78	RNase H I
15b	278693648	79	80	RNase H I
15c	278480974	81	82	RNase H I
15d	278498047	83	84	RNase H I
15e	CG144997-02	85	86	RNaseHI
16a	CG145494-01	87	88	PRESTIN
17a	CG145722-01	89	90	WEE1
18a	CG145754-01	91	92	Kallikrein 7 Precursor
18b	CG145754-03	93	94	Kallikrein 7 Precursor
18c	CG145754-02	95	96	Kallikrein 7 Precursor
18d	252718128	97	98	Kallikrein
18e	252718152	99	100	Kallikrein
18f	247856668	101	102	Kallikrein 7 Precursor
18g	247856705	103	104	Kallikrein 7 Precursor
19a	CG146279-01	105	106	Novel Potassium Channel Subfamily K
				Member 10 (TREK-2)
20a	CG146374-01	107	108	Glycogen Branching Enzyme
21a	CG146403-01	109	110	Diacylglycerol Acyltransferase 2
22a	CG146513-01	111	112	Diacyiglycerol Acyltransferase 2
23a	CG146522-01	113	114	Diacyiglycerol Acyltransferase 2
24a	CG146531-01	115	116	Diacylglycerol Acyltransferase 2
25a	CG147274-01	117	118	Protease
26a	CG147351-01	119	120	Testis-Development Related NYD-SP27
27a	CG147419-01	121	122	Glutamine: Fructose-6-Phosphate
				Amidotransferase 1 Muscle Isoform
28a	CG148102-01	123	124	Carnitine 0-Palmitoyltransferase
28b	CG148102-02	125	126	Carnitine 0-Palmitoyltransferase
29a	CG148431-01	127	128	Class II Aminotransferase
29b	CG148431-02	129	130	Class II Aminotransferase
30a	CG148888-01	131	132	GALNAC 4-Sulfotransferase
31a	CG149008-01	133	134	Sodium/Hydrogen Exchanger
32a	CG149350-01	135	136	Vacuolar ATP Synthase Subunit F
32b	CG149350-02	137	138	Vacuolar ATP Synthase Subunit F
33a	CG149463-01	139	140	Serine/Threonine-Protein Kinase SGK
34a	CG149536-01	141	142	Protein-Tyrosine Phosphatase,
				Non-Receptor Type 2
35a	CG149964-01	143	144	Brain Mitochondrial Carrier Protein-1
35b	309326356	145	146	Brain Mitochondrial Carrier Protein-1
35c	309326444	147	148	Brain Mitochondrial Carrier Protein-1
35d	309326473	149	150	Brain Mitochondrial Carrier Protein-1
35e	CG149964-02	151	152	Brain Mitochondrial Carrier Protein-1
36a	CG150306-01	153	154	Dual Specificity Protein Phosphatase 5
37a	CG150510-01	155	156	Human Alpha-2,3-Sialyltransferase
38a	CG150704-01	157	158	Testis ecto-ADP-Ribosyltransferase
				Precursor
39a	CG150799-01	159	160	MASS1
39b	CG150799-02	161	162	MASS1
39c	CG150799-03	163	164	MASS1
39d	CG150799-01	165	166	MASS1
40a	CG1S1O14-01	167	168	Metabotropic Glutamate Receptor 3
40b	CG151014-02	169	170	Metabotropic Glutamate Receptor 3
40c	CG151014-03	171	172	Metabotropic Glutamate Receptor 3
41a	CG151297-01	173	174	Calmodulin-Dependent
				Phosphodiesterase
41b	CG151297-02	175	176	Calmodulin-Dependent
				Phosphodiesterase
42a	CG151822-01	177	178	Prenylcysteine Carboxyl
				Methyltransferase
42b	CG151822-02	179	180	Prenylcysteine Carboxyl
				Methyltransferase
43a	CG152256-01	181	182	Phosphatidylserine Synthase
44a	CG171804-01	183	184	N-Acetylgalactosaminide Alpha 2,
				6-Sialyltransferase
45a	CG171841-01	185	186	Iron-Containing Alcohol Dehydrogenase
46a	CG173017-01	187	188	Retinoic Acid Receptor RXR-Beta
47a	CG173347-01	189	190	Serum Paraoxonase/Arylesterase 3
48a	CG56234-01	191	192	Phosphoenolpyruvate Carboxykinase 2
				(PCK2)
48b	CG56234-02	193	194	Phosphoenolpyruvate Carboxykinase 2
				(PCK2)
49a	CG56836-01	195	196	Cathepsin B
49b	CG56836-02	197	198	Cathepsin B
49c	CG56836-03	199	200	Cathepsin B
49d	CG56836-04	201	202	Cathepsin B
49e	247856403	203	204	Cathepsin B
49f	247856434	205	206	Cathepsin B
49g	247856497	207	208	Cathepsin B
49h	247856493	209	210	Cathepsin B
49i	247856574	211	212	Cathepsin B
49j	247856545	213	214	Cathepsin B
49k	275480714	215	216	Cathepsin B
50a	CG57284-01	217	218	RAS-Related Protein RAB-5C
50b	CG57284-03	219	220	RAS-Related Protein RAB-5C
50c	CG57284-02	221	222	RAS-Related Protein RAB-5C
51a	CG57308-01	223	224	Sulfonylurea Receptor 1
51b	CG57308-02	225	226	Sulfonylurea Receptor 1
52a	CG93659-01	227	228	Mitogen-Activated Protein Kinase
				Kinase Kinase 8
52b	CG93659-03	229	230	Mitogen-Activated Protein Kinase
				Kinase Kinase 8
52c	CG93659-02	231	232	Mitogen-Activated Protein Kinase
				Kinase Kinase 8
53a	CG94521-01	233	234	Cytoplasmic Glycerol-3-Phosphate
				Dehydrogenase [NAD+]
53b	CG94521-03	235	236	Cytoplasmic Glycerol-3-Phosphate
				Dehydrogenase [NAD+]
53c	CG94521-02	237	238	Cytoplasmic Glycerol-3-Phosphate
				Dehydrogenase [NAD+]
54a	CG96613-01	239	240	Pyruvate Dehydrogenase Kinase (PDK1)
54b	CG96613-03	241	242	Pyruvate Dehydrogenase Kinase (PDK1)
54c	CG96613-02	243	244	Pyruvate Dehydrogenase Kinase (PDK1)
55a	CG96736-01	245	246	Neutral Amino Acid Transporter B
55b	CG96736-02	247	248	Neutral Amino Acid Transporter B

[0024] 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.

[0025] Pathologies, diseases, disorders and condition and the like that are associated with NOVX sequences include, but are not limited to: e.g., 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.

[0026] 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.

[0027] 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.

[0028] 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.

[0029] 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.

[0030] Additional utilities for NOVX nucleic acids and polypeptides according to the invention are disclosed herein.

[0031] NOVX Clones

[0032] 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.

[0033] 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.

[0034] 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.

[0035] 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 124; (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 124, 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 124; (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 124 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).

[0036] 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 124; (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 124 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 124; (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 124, 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 124 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.

[0037] 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 124; (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 124 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 124; 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 124 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.

[0038] NOVX Nucleic Acids and Polypeptides

[0039] 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.

[0040] 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.

[0041] 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.

[0042] 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.

[0043] 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 124, 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 124, 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.)

[0044] 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.

[0045] 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 124, or a complement thereof. Oligonucleotides may be chemically synthesized and may also be used as probes.

[0046] 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 124, 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 124, is one that is sufficiently complementary to the nucleotide sequence of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 124, 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 124, thereby forming a stable duplex.

[0047] 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 intermnediates.

[0048] 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.

[0049] 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.

[0050] 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.

[0051] 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.

[0052] 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 124, as well as a polypeptide possessing NOVX biological activity. Various biological activities of the NOVX proteins are described below.

[0053] 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 bonafide cellular protein, a minimum size requirement is often set, e.g., a stretch of DNA that would encode a protein of 50 amino acids or more.

[0054] 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 124; or an anti-sense strand nucleotide sequence of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 124; or of a naturally occurring mutant of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 124.

[0055] 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.

[0056] “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 124, 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.

[0057] NOVX Nucleic Acid and Polypeptide Variants

[0058] 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 124, 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 124. 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 124.

[0059] In addition to the human NOVX nucleotide sequences of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 124, 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.

[0060] 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 124, 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.

[0061] 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 124. 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.

[0062] 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.

[0063] 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.

[0064] 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 124, corresponds to a naturally-occurring nucleic acid molecule. As used herein, a “naturally-occuring” nucleic acid molecule refers to an RNA or DNA molecule having a nucleotide sequence that occurs in nature (e.g., encodes a natural protein).

[0065] 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 124, 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, N.Y., and Krieger, 1990; GENE TRANSFER AND EXPRESSION, A LABORATORY MANUAL, Stockton Press, N.Y.

[0066] 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 124, or fragments, analogs or derivatives thereof, under conditions of low stringency, is provided. A non-limiting example of low stringency hybridization conditions are hybridization in 35% formamide, 5×SSC, 50 mM Tris-HCl (pH 7.5), 5 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.2% BSA, 100 mg/ml denatured salmon sperm DNA, 10% (wt/vol) dextran sulfate at 40° C., followed by one or more washes in 2×SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS at 50° C. Other conditions of low stringency that may be used are well known in the art (e.g., as employed for cross-species hybridizations). See, e.g., Ausubel, et al. (eds.), 1993, CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, N.Y., and Kriegler, 1990, GENE TRANSFER AND EEPRESSION, A LABORATORY MANUAL, Stockton Press, N.Y.; Shilo and Weinberg, 1981. Proc Natl Acad Sci USA 78: 6789-6792.

[0067] Conservative Mutations

[0068] 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 124, 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 124. 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.

[0069] 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 124, 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 124. 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 124; more preferably at least about 70% homologous to SEQ ID NO: 2n, wherein n is an integer between 1 and 124; still more preferably at least about 80% homologous to SEQ ID NO: 2n, wherein n is an integer between 1 and 124; even more preferably at least about 90% homologous to SEQ ID NO: 2n, wherein n is an integer between 1 and 124; and most preferably at least about 95% homologous to SEQ ID NO: 2n, wherein n is an integer between 1 and 124.

[0070] 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 124, 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 124, such that one or more amino acid substitutions, additions or deletions are introduced into the encoded protein.

[0071] Mutations can be introduced any one of SEQ ID NO: 2n−1, wherein n is an integer between 1 and 124, 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, senne, 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 124, the encoded protein can be expressed by any recombinant technology known in the art and the activity of the protein can be determined.

[0072] 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.

[0073] 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).

[0074] 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).

[0075] Interfering RNA

[0076] 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.

[0077] 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.

[0078] 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.

[0079] 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.

[0080] 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 lmgenex). 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 thyrmidines. 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.

[0081] 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.

[0082] 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.

[0083] 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.

[0084] 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.

[0085] 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.

[0086] 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.

[0087] 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.

[0088] 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.

[0089] 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.

[0090] 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 the 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.

[0091] 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.

[0092] 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.

[0093] 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 polynuclectide 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.

[0094] 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.

[0095] Production of RNAs

[0096] 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).

[0097] Lysate Preparation

[0098] 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.

[0099] 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.

[0100] 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.

[0101] RNA Preparation

[0102] 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)).

[0103] 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.

[0104] Cell Culture

[0105] 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.

[0106] 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.

[0107] Antisense Nucleic Acids

[0108] 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 124, 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 124, 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 124, are additionally provided.

[0109] 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).

[0110] 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).

[0111] 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, 5-(carboxyhydroxylmethyl) uracil, 5-carboxymethylaminomethyluracil, dihydrouracil, beta-D-galactosylqueosine, inosine, N6-isopentenyladenine, 1-methylguanine, 1-methylinosine, 2,2-dimethylguanine, 2-methyladenine, 2-methylguanine, 5-methoxyuracil, 3-methylcytosine, 5-methylcytosine, N6-adenine, 7-methylguanine, 5-methylaminomethyluracil, 5-methoxyaminomethyl-2-thiouracil, 2-thiouracil, 4-thiouracil, beta-D-mannosylqueosine, 5′-methoxycarboxymethyluracil, 2-methylthio-N6-isopentenyladenine, uracil-5-oxyacetic acid (v), wybutoxosine, pseudouracil, queosine, 2-thiocytosine, 5-methyl-2-thiouracil, 5-methyluracil, uracil-5-oxyacetic acid methylester, uracil-5-oxyacetic acid (v), 5-methyl-2-thiouracil, 3-(3-amino-3-N-2-carboxypropyl) uracil, (acp3)w, and 2,6-diaminopurine. Alternatively, the antisense nucleic acid can be produced biologically using an expression vector into which a nucleic acid has been subcloned in an antisense orientation (i.e., RNA transcribed from the inserted nucleic acid will be of an antisense orientation to a target nucleic acid of interest, described further in the following subsection).

[0112] 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.

[0113] In yet another embodiment, the antisense nucleic acid molecule of the invention is an (x-anomeric nucleic acid molecule. An α-anomeric nucleic acid molecule forms specific double-stranded hybrids with complementary RNA in which, contrary to the usual 0-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.

[0114] Ribozymes and PNA Moieties

[0115] 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.

[0116] 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 124). 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.

[0117] 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.

[0118] 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 performned 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.

[0119] 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).

[0120] 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.

[0121] 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. Nati. 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. Pharnn. 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.

[0122] NOVX Polypeptides

[0123] 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 124. 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 124, while still encoding a protein that maintains its NOVX activities and physiological functions, or a functional fragment thereof.

[0124] 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.

[0125] 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.

[0126] 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.

[0127] 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.

[0128] 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 124) 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.

[0129] 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.

[0130] In an embodiment, the NOVX protein has an amino acid sequence of SEQ ID NO: 2n, wherein n is an integer between 1 and 124. In other embodiments, the NOVX protein is substantially homologous to SEQ ID NO: 2n, wherein n is an integer between 1 and 124, and retains the functional activity of the protein of SEQ ID NO: 2n, wherein n is an integer between 1 and 124, 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 124, and retains the functional activity of the NOVX proteins of SEQ ID NO: 2n, wherein n is an integer between 1 and 124.

[0131] Determining Homology Between Two or More Sequences

[0132] 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”).

[0133] 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 124.

[0134] 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.

[0135] Chimeric and Fusion Proteins

[0136] 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 124, 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.

[0137] 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.

[0138] 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.

[0139] 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.

[0140] 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, PCR amplification of gene fragments can be carried out using anchor primers that give rise to complementary overhangs between two consecutive gene fragments that can subsequently be annealed and reamplified to generate a chimeric gene sequence (see, e.g., Ausubel, et al. (eds.) CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, 1992). Moreover, many expression vectors are commercially available that already encode a fusion moiety (e.g., a GST polypeptide). 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.

[0141] NOVX Agonists and Antagonists

[0142] 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.

[0143] 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.

[0144] Polypeptide Libraries

[0145] 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.

[0146] 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.

[0147] Anti-NOVX Antibodies

[0148] 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.

[0149] 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 124, 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.

[0150] 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.

[0151] 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.

[0152] 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.

[0153] 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, NY, incorporated herein by reference). Some of these antibodies are discussed below.

[0154] Polyclonal Antibodies

[0155] 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).

[0156] 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).

[0157] Monoclonal Antibodies

[0158] 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.

[0159] 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.

[0160] 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.

[0161] 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, California and the American Type Culture Collection, Manassas, Virginia. 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).

[0162] 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.

[0163] 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.

[0164] 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.

[0165] 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.

[0166] Humanized Antibodies The antibodies directed against the protein antigens of the invention can further comprise humanized antibodies or human antibodies. These antibodies are suitable for administration to humans without engendering an immune response by the human against the administered immunoglobulin. Humanized forms of antibodies are chimeric immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab′, F(ab′)2 or other antigen-binding subsequences of antibodies) that are principally comprised of the sequence of a human immunoglobulin, and contain minimal sequence derived from a non-human immunoglobulin. Humanization can be performed following the method of Winter and co-workers (Jones et al., Nature, 321:522-525 (1986); Riechmann et al., Nature, 332:323-327 (1988); Verhoeyen et al., Science, 239:1534-1536 (1988)), by substituting rodent CDRs or CDR sequences for the corresponding sequences of a human antibody. (See also U.S. Pat. No. 5,225,539.) In some instances, Fv framework residues of the human immunoglobulin are replaced by corresponding non-human residues. Humanized antibodies can also comprise residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences. In general, the humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or substantially all of the framework regions are those of a human immunoglobulin consensus sequence. The humanized antibody optimally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin (Jones et al., 1986; Riechmann et al., 1988; and Presta, Curr. Op. Struct. Biol., 2:593-596 (1992)).

[0167] Human Antibodies

[0168] Fully human antibodies essentially relate to antibody molecules in which the entire sequence of both the light chain and the heavy chain, including the CDRs, arise from human genes. Such antibodies are termed “human antibodies”, or “fully human antibodies” herein. Human monoclonal antibodies can be prepared by the trioma technique; the human B-cell hybridoma technique (see Kozbor, et al., 1983 Immunol Today 4: 72) and the EBV hybridoma technique to produce human monoclonal antibodies (see Cole, et al., 1985 In: MONOCLONAL ANTIBODIES AND CANCER THERAPY, Alan R. Liss, Inc., pp. 77-96). Human monoclonal antibodies may be utilized in the practice of the present invention and may be produced by using human hybridomas (see Cote, et al., 1983. Proc Natl Acad Sci USA 80: 2026-2030) or by transforming human B-cells with Epstein Barr Virus in vitro (see Cole, et al., 1985 In: MONOCLONAL ANTIBODIES AND CANCER THERAPY, Alan R. Liss, Inc., pp. 77-96).

[0169] 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)).

[0170] 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.

[0171] 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.

[0172] 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.

[0173] 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.

[0174] Fab Fragments and Single Chain Antibodies

[0175] 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) F, fragments.

[0176] Bispecific Antibodies

[0177] 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.

[0178] 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 13 May 1993, and in Traunecker et al., EMBO J., 10:3655-3659 (1991).

[0179] 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).

[0180] 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.

[0181] Bispecific antibodies can be prepared as full length antibodies or antibody fragments (e.g. F(ab′)2 bispecific antibodies). Techniques for generating bispecific antibodies from antibody fragments have been described in the literature. For example, bispecific antibodies can be prepared using chemical linkage. Brennan et al., Science 229:81 (1985) describe a procedure wherein intact antibodies are proteolytically cleaved to generate F(ab′)2 fragments. These fragments are reduced in the presence of the dithiol complexing agent sodium arsenite to stabilize vicinal dithiols and prevent intermolecular disulfide formation. The Fab′ fragments generated are then converted to thionitrobenzoate (TNB) derivatives. One of the Fab′-TNB derivatives is then reconverted to the Fab′-thiol by reduction with mercaptoethylamine and is mixed with an equimolar amount of the other Fab′-TNB derivative to form the bispecific antibody. The bispecific antibodies produced can be used as agents for the selective immobilization of enzymes.

[0182] 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.

[0183] 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).

[0184] Antibodies with more than two valencies are contemplated. For example, trispecific antibodies can be prepared. Tutt et al., J. Immunol. 147:60 (1991).

[0185] Exemplary bispecific antibodies can bind to two different epitopes, at least one of which originates in the protein antigen of the invention. Alternatively, an anti-antigenic arm of an immunoglobulin molecule can be combined with an arm which binds to a triggering molecule on a leukocyte such as a T-cell receptor molecule (e.g. CD2, CD3, CD28, or B7), or Fc receptors for IgG (FcγR), such as FcγRI (CD64), FcγRII (CD32) and FcyRIII (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).

[0186] Heteroconjugate Antibodies

[0187] 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.

[0188] Effector Function Engineering

[0189] 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).

[0190] Immunoconjugates

[0191] 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).

[0192] Chemotherapeutic agents useful in the generation of such immunoconjugates have been described above. Enzymatically active toxins and fragments thereof that can be used include diphtheria A chain, nonbinding active fragments of diphtheria toxin, exotoxin A chain (from Pseudomonas aeruginosa), ricin A chain, abrin A chain, modeccin A chain, alpha-sarcin, Aleurites fordii proteins, dianthin proteins, Phytolaca americana proteins (PAPI, PAPII, and PAP-S), momordica charantia inhibitor, curcin, crotin, sapaonaria officinalis inhibitor, gelonin, mitogellin, restrictocin, phenomycin, enomycin, and the tricothecenes. A variety of radionuclides are available for the production of radioconjugated antibodies. Examples include 212Bi, 131I, 131In, 90Y, and 186Re.

[0193] 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.

[0194] 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.

[0195] Immunoliposomes

[0196] The antibodies disclosed herein can also be formnulated 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.

[0197] 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).

[0198] Diagnostic Applications of Antibodies Directed Against the Proteins of the Invention

[0199] 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.

[0200] 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”).

[0201] 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 avidintbiotin; 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 or3H.

[0202] Antibody Therapeutics

[0203] 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.

[0204] 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.

[0205] 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.

[0206] Pharmaceutical Compositions of Antibodies

[0207] Antibodies specifically binding a protein of the invention, as well as other molecules identified by the screening assays disclosed herein, can be administered for the treatment of various disorders in the form of pharmaceutical compositions. Principles and considerations involved in preparing such compositions, as well as guidance in the choice of components are provided, for example, in Remington: The Science And Practice Of Pharmacy 19th ed. (Alfonso R. Gennaro, et al., editors) Mack Pub. Co., Easton, Pa.: 1995; Drug Absorption Enhancement: Concepts, Possibilities, Limitations, And Trends, Harwood Academic Publishers, Langhorne, Pa., 1994; and Peptide And Protein Drug Delivery (Advances In Parenteral Sciences, Vol. 4), 1991, M. Dekker, New York.

[0208] 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.

[0209] 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.

[0210] The formulations to be used for in vivo administration must be sterile. This is readily accomplished by filtration through sterile filtration membranes.

[0211] 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.

[0212] ELISA Assay

[0213] 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.

[0214] NOVX Recombinant Expression Vectors and Host Cells

[0215] 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.

[0216] 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).

[0217] 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.).

[0218] The recombinant expression vectors of the invention can be designed for expression of NOVX proteins in prokaryotic or eukaryotic cells. For example, NOVX proteins can be expressed in bacterial cells such as Escherichia coli, insect cells (using baculovirus expression vectors) yeast cells or mammalian cells. Suitable host cells are discussed further in Goeddel, GENE EXPRESSION TECHNOLOGY: METHODS IN ENZYMOLOGY 185, Academic Press, San Diego, Calif. (1990). Alternatively, the recombinant expression vector can be transcribed and translated in vitro, for example using T7 promoter regulatory sequences and T7 polymerase.

[0219] 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.

[0220] 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).

[0221] 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 mN 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.

[0222] In another embodiment, the NOVX expression vector is a yeast expression vector. Examples of vectors for expression in yeast Saecharomyces 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.).

[0223] 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).

[0224] 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.

[0225] 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 (x-fetoprotein promoter (Campes and Tilghman, 1989. Genes Dev. 3: 537-546).

[0226] 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.

[0227] 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.

[0228] 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.

[0229] 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.

[0230] 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).

[0231] 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.

[0232] Transgenic NOVX Animals

[0233] 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.

[0234] 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 124, 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.

[0235] 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 124), 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 124, 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).

[0236] 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.

[0237] 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.

[0238] 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.

[0239] 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 Go 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.

[0240] Pharmaceutical Compositions

[0241] 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.

[0242] 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.

[0243] 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.

[0244] 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.

[0245] 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 exciplent 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.

[0246] 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.

[0247] Systemic administration can also be by transmucesal 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.

[0248] 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.

[0249] 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.

[0250] 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.

[0251] 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.

[0252] The pharmaceutical compositions can be included in a container, pack, or dispenser together with instructions for adminnistration.

[0253] Screening and Detection Methods

[0254] 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.

[0255] The invention further pertains to novel agents identified by the screening assays described herein and uses thereof for treatments as described, supra.

[0256] Screening Assays

[0257] 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.

[0258] 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.

[0259] 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.

[0260] 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.

[0261] 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.).

[0262] 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.

[0263] 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.

[0264] 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.

[0265] 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.

[0266] 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.

[0267] 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.

[0268] 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).

[0269] 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.

[0270] 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 Chernicals, 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.

[0271] 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.

[0272] 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.

[0273] 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.

[0274] The invention further pertains to novel agents identified by the aforementioned screening assays and uses thereof for treatments as described herein.

[0275] Detection Assays

[0276] 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.

[0277] Chromosome Mapping

[0278] 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 124, 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.

[0279] 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.

[0280] 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.

[0281] 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.

[0282] 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).

[0283] 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.

[0284] 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.

[0285] 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.

[0286] Tissue Typing

[0287] 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).

[0288] 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.

[0289] 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).

[0290] 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 124, are used, a more appropriate number of primers for positive individual identification would be 500-2,000.

[0291] Predictive Medicine

[0292] 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.

[0293] Another aspect of the invention provides methods for determining NOVX protein, nucleic acid expression or activity in an individual to thereby select appropriate therapeutic or prophylactic agents for that individual (referred to herein as “pharmacogenomics”). Pharmacogenomics allows for the selection of agents (e.g., drugs) for therapeutic or prophylactic treatment of an individual based on the genotype of the individual (e.g., the genotype of the individual examined to determine the ability of the individual to respond to a particular agent.)

[0294] 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.

[0295] These and other agents are described in further detail in the following sections.

[0296] Diagnostic Assays

[0297] An exemplary method for detecting the presence of 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 124, 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.

[0298] 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.

[0299] 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.

[0300] 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.

[0301] 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.

[0302] Prognostic Assays

[0303] 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.

[0304] 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).

[0305] 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.

[0306] 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.

[0307] 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.

[0308] 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.

[0309] 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.

[0310] 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).

[0311] 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 waith 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.

[0312] 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.

[0313] 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.

[0314] 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.

[0315] 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.

[0316] 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.

[0317] 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.

[0318] 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.

[0319] Pharmacogenomics

[0320] 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.

[0321] 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.

[0322] 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.

[0323] 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.

[0324] 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.

[0325] Monitoring of Effects During Clinical Trials

[0326] 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.

[0327] 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.

[0328] 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.

[0329] Methods of Treatment

[0330] 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.

[0331] These methods of treatment will be discussed more fully, below.

[0332] Diseases and Disorders

[0333] 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.

[0334] 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.

[0335] 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).

[0336] Prophylactic Methods

[0337] 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.

[0338] Therapeutic Methods

[0339] 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.

[0340] 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).

[0341] Determination of the Biological Effect of the Therapeutic

[0342] 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.

[0343] 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.

[0344] Prophylactic and Therapeutic Uses of the Compositions of the Invention

[0345] 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.

[0346] 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.

[0347] 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.

[0348] 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: Polynucleotide and Polypeptide Sequences, and Homology Data

Example 1

[0349] 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	6189 bp
NOV1a,	ATGTTGAAGTTCAAATATGGAGCGCGGAATCCTTTGGATGCTGGTGCTGCTGAACCCATTGCCAGCCG
CG106764-01
DNA Sequence	GGCCTCCAGGCTGAATCTGTTCTTCCAGGGGAAACCACCCTTTATGACTCAACAGCAGATGTCTCCTC
	TTTCCCGAGAAGGGATATTAGATGCCCTCTTTGTTCTCTTTGAAGAATGCAGTCAGCCTGCTCTGATG
	AAGATTAAGCACGTGAGCAACTTTGTCCGGAAGTGTTCCGACACCATAGCTGAGTTACAGGAGCTCCA
	GCCTTCGGCAAAGGACTTCGAAGTCAGAAGTCTTGTAGGTTGTGGTCACTTTGCTGAAGTGCAGGTGG
	TAAGAGAGAAAGCAACCGGGGACATCTATGCTATGAAAGTGATGAAGAAGAAGGCTTTATTGGCCCAG
	GAGCAGGTTTCATTTTTTGAGGAAGAGCGGAACATATTATCTCGAAGCACAAGCCCGTGGATCCCCCA
	ATTACAGTATGCCTTTCAGGACAAAAATCACCTTTATCTGGTGATGGAATATCAGCCTGGAGGGGACT
	TGCTGTCACTTTTGAATAGATATGAGGACCAGTTAGATGAAAACCTGATACAGTTTTACCTAGCTGAG
	CTGATTTTGGCTGTTCACAGCGTTCATCTGATGGGATACGTGCATCGGGACATCAAGCCTGAGAACAT
	TCTCGTTGACCGCACAGGACACATCAAGCTGGTGGATTTTGGATCTGCCGCGAAAATGAATTCAAACA
	AGGTGAATGCCAAACTCCCGATTGGGACCCCAGATTACATGGCTCCTGAAGTGCTGACTGTGATGAAC
	GGGGATGGAAAAGGCACCTACGGCCTGGACTGTGACTGGTGGTCAGTGGGCGTGATTGCCTATGAGAT
	GATTTATGGGAGATCCCCCTTCGCAGAGGGAACCTCTGCCAGAACCTTCAATAACATTATGAATTTCC
	AGCGGTTTTTGAAATTTCCAGATGACCCCAAAGTGAGCAGTGACTTTCTTGATCTGATTCAAAGCTTG
	TTGTGCGGCCAGAAAGAGAGACTGAAGTTTGAAGGTCTTTGCTGCCATCCTTTCTTCTCTAAAATTGA
	CTGGAACAACATTCGTAACGCTCCTCCCCCCTTCGTTCCCACCCTCAAGTCTGACGATGACACCTCCA
	ATTTTGATGAACCAGAGAAGAATTCGTGGGTTTCATCCTCTCCGTGCCAGCTGAGCCCCTCAGGCTTC
	TCGGGTGAAGAACTGCCGTTTGTGGGGTTTTCGTACAGCAAGGCACTGGGGATTCTTGGTAGATCTGA
	GTCTGTTGTGTCGGGTCTGGACTCCCCTGCCAAGACTAGCTCCATGGAAAAGAAACTTCTCATCAAAA
	GCAAAGAGCTACAAGACTCTCAGGACAAGTGTCACAAGATGGAGCAGGAAATGACCCGGTTACATCGG
	AGAGTGTCAGAGGTGGAGGCTGTGCTTAGTCAGAAGGAGGTGGAGCTGAAGGCCTCTGAGACTCAGAG
	ATCCCTCCTGGAGCAGGACCTTGCTACCTACATCACAGAATGCAGTAGCTTAAAGCGAAGTTTGGAGC
	AAGCACGGATGGAGGTGTCCCAGGAGGATGACAAAGCACTGCAGCTTCTCCATGATATCAGAGAGCAG
	AGCCGGAAGCTCCAAGAAATCAAAGAGCAGGAGTACCAGGCTCAAGTGGAAGAAATGAGGTTGATGAT
	GAATCAGTTGGAAGAGGATCTTGTCTCAGCAAGAAGACGGAGTGATCTCTACGAATCTGAGCTGAGAG
	AGTCTCGGCTTGCTGCTGAAGAATTCAAGCGGAAAGCGACAGAATGTCAGCATAAACTGTTGAAGGCT
	AAGGATCAGGGGAAGCCTGAAGTGGGAGAATATGCGAAACTGGAGAAGATCAATGCTGAGCAGCAGCT
	CAAAATTCAGGAGCTCCAAGAGAAACTGGAGAAGGCTGTAAAAGCCAGCACGGAGGCCACCGAGCTGC
	TGCAGAATATCCGCCAGGCAAAGGAGCGAGCCGAGAGGGAGCTGGAGAAGCTGCAGAACCGAGAGGAT
	TCTTCTGAAGGCATCAGAAAGAAGCTGGTGGAAGCTGAGGAACGCCGCCATTCTCTGGAGAACAAGGT
	AAAGAGACTAGAGACCATGGAGCGTAGAGAAAACAGACTGAAGGATGACATCCAGACAAAATCCCAAC
	AGATCCAGCAGATGGCTGATAAAATTCTGGAGCTCGAAGAGAAACATCGGGAGGCCCAAGTCTCAGCC
	CAGCACCTAGAAGTGCACCTGAAACAGAAAGAGCAGCACTATGAGGAAAAGATTAAAGTATTGGACAA
	TCAGATAAAGAAAGACCTGGCTGACAAGGAGACACTGGAGAACATGATGCAGAGACACGAGGAGGAGG
	CCCATGAGAAGGGCAAAATTCTCAGCGAACAGAAGGCGATGATCAATGCTATGGATTCCAAGATCAGA
	TCCCTGGAACAGAGGATTGTGGAACTGTCTGAAGCCAATAAACTTGCAGCAAATAGCAGTCTTTTTAC
	CCAAAGGAACATGAAGGCCCAAGAAGAGATGATTTCTGAACTCAGGCAACAGAAATTTTACCTGGAGA
	CACAGGCTGGGAAGTTGGAGGCCCAGAACCGAAAACTGGAGGAGCAGCTGGAGAAGATCAGCCACCAA
	GACCACAGTGACAAGAATCGGCTGCTGGAACTGGAGACAAGATTGCGGGAGGTGAGTCTAGAGCACGA
	GGAGCAGAAACTGGAGCTCAAGCGCCAGCTCACAGAGCTACAGCTCTCCCTGCAGGAGCGCGAGTCAC
	AGTTGACAGCCCTGCAGGCTGCACGGGCGGCCCTGGAGAGCCAGCTTCGCCAGGCGAAGACAGAGCTG
	GAAGAGACCACAGCAGAAGCTGAAGAGGAGATCCAGGCACTCACGGCACATAGAGATGAAATCCAGCG
	CAAATTTGATGCTCTTCGTAACAGCTGTACTGTGATCACAGACCTGGAGGAGCAGCTAAACCAGCTGA
	CCGAGGACAACGCTGAACTCAACAACCAAAACTTCTACTTGTCCAAACAACTCGATGAGGCTTCTGGC
	GCCAACGACGAGATTGTACAACTGCGAAGTGAAGTGGACCATCTCCGCCGGGAGATCACGGAACGAGA
	GATGCAGCTTACCAGCCAGAAGCAAACGATGGAGGCTCTGAAGACCACGTGCACCATGCTGGAGGAAC
	AGGTCATGGATTTGGAGGCCCTAAACGATGAGCTGCTAGAAAAAGAGCGGCAGTGGGAGGCCTGGAGG
	AGCGTCCTGGGTGATGAGAAATCCCAGTTTGAGTGTCGGGTTCGAGAGCTGCAGAGGATGCTGGACAC
	CGAGAAACAGAGCAGGGCGAGAGCCGATCAGCGGATCACCGAGTCTCGCCAGGTGGTGGAGCTGGCAG
	TGAAGGAGCACAAGGCTGAGATTCTCGCTCTGCAGCAGGCTCTCAAAGAGCAGAAGCTGAAGGCCGAG
	AGCCTCTCTGACAAGCTCAATGACCTGGAGAAGAAGCATGCTATGCTTGAAATGAATGCCCGAAGCTT
	ACAGCAGAAGCTGGAGACTGAACGAGAGCTCAAACAGAGGCTTCTGGAAGAGCAAGCCAAATTACAGC
	AGCAGATGGACCTGCAGAAAAATCACATTTTCCGTCTGACTCAAGGACTGCAAGAAGCTCTAGATCGG
	GCTGATCTACTGAAGACAGAAAGAAGTGACTTGGAGTATCAGCTGGAAAACATTCAGGTGCTCTATTC
	TCATGAAAAGGTGAAAATGGAAGGCACTATTTCTCAACAAACCAAACTCATTGATTTTCTGCAAGCCA
	AAATGGACCAACCTGCTAAAAAGAAAAAGGTGCCTCTGCAGTACAATGAGCTGAAGCTGGCCCTGGAG
	AAGGAGAAAGCTCGCTGTGCAGAGCTAGAGGAAGCCCTTCAGAAGACCCGCATCGAGCTCCGGTCCGC
	CCGGGAGGAAGCTGCCCACCGCAAAGCAACGGACCACCCACACCCATCCACGCCAGCCACCGCGAGGC
	AGCAGATCGCCATGTCTGCCATCGTGCGGTCGCCAGAGCACCAGCCCAGTGCCATGAGCCTGCTGGCC
	CCGCCATCCAGCCGCAGAAAGGAGTCTTCAACTCCAGAGGAATTTAGTCGGCGTCTTAAGGAACGCAT
	GCACCACAATATTCCTCACCGATTCAACGTAGGACTGAACATGCGAGCCACAAAGTGTGCTGTGTGTC
	TGGATACCGTGCACTTTGGACGCCAGGCATCCAAATGTCTAGAATGTCAGGTGATGTGTCACCCCAAG
	TGCTCCACGTGCTTGCCAGCCACCTGCGGCTTGCCTGCTGAATATGCCACACACTTCACCGAGGCCTT
	CTGCCGTGACAAAATGAACTCCCCAGGTCTCCAGACCAAGGAGCCCAGCAGCAGCTTGCACCTGGAAG
	GGTGGATGAAGGTGCCCAGGAATAACAAACGAGGACAGCAAGGCTGGGACAGGAAGTACATTGTCCTG
	GAGGGATCAAAAGTCCTCATTTATGACAATGAAGCCAGAGAAGCTGGACAGAGGCCGGTGGAAGAATT
	TGAGCTGTGCCTTCCCGACGGGGATGTATCTATTCATGGTGCCGTTGGTGCTTCCGAACTCGCAAATA
	CAGCCAAAGCAGATGTCCCATACATACTGAAGATGGAATCTCACCCGCACACCACCTGCTGGCCCGGG
	AGAACCCTCTACTTGCTAGCTCCCAGCTTCCCTGACAAACAGCGCTGGGTCACCGCCTTAGAATCAGT
	TGTCGCAGGTGGGAGAGTTTCTAGGGAAAAAGCAGAAGCTGATGCTAAACTGCTTGGAAACTCCCTGC
	TGAAACTGGAAGGTGATGACCGTCTAGACATGAACTGCACGCTGCCCTTCAGTGACCAGGTAGTGTTG
	GTGGGCACCGAGGAAGGGCTCTACGCCCTGAATGTCTTGAAAAACTCCCTAACCCATGTCCCAGGAAT
	TGGAGCAGTCTTCCAAATTTATATTATCAAGGACCTGGAGAAGCTACTCATGATAGCAGGTGAAGAGC
	GGGCACTGTGTCTTGTGGACGTGAAGAAAGTGAAACAGTCCCTGGCCCAGTCCCACCTGCCTGCCCAG
	CCCGACATCTCACCCAACATTTTTGAAGCTGTCAAGGGCTGCCACTTGTTTGGGGCAGGCAAGATTGA
	GAACGGGCTCTGCATCTGTGCAGCCATGCCCAGCAAAGTCGTCATTCTCCGCTACAACGAAAACCTCA
	GCAAATACTGCATCCGGAAAGAGATAGAGACCTCAGAGCCCTGCAGCTGTATCCACTTCACCAATTAC
	AGTATCCTCATTGGAACCAATAAATTCTACGAAATCGACATGAAGCAGTACACGCTCGAGGAATTCCT
	GGATAAGAATGACCATTCCTTGGCACCTGCTGTGTTTGCCGCCTCTTCCAACAGCTTCCCTGTCTCAA
	TCGTGCAGGTGAACAGCGCAGGGCAGCGAGAGGAGTACTTGCTGTGTTTCCACGAATTTGGAGTGTTC
	GTGGATTCTTACGGAAGACGTAGCCGCACAGACGATCTCAAGTGGAGTCGCTTACCTTTGGCCTTTGC
	CTACAGAGAACCCTATCTGTTTGTGACCCACTTCAACTCACTCGAAGTAATTGAGATCCAGGCACGCT
	CCTCAGCAGGGACCCCTGCCCGAGCGTACCTGGACATCCCGAACCCGCGCTACCTGGGGCCTGCCATT
	TCCTCAGGAGCGATTTACTTGGCGTCCTCATACCAGGATAAATTAAGGGTCATTTGCTGCAAGGGAAA
	CCTCGTGAAGGAGTCCGGCACTGAACACCACCGGGGCCCGTCCACCTCCCGCAGCAGCCCCAACAAGC
	GAGGCCCACCCACGTACAACGAGCACATCACCAAGCGCGTGGCCTCCAGCCCAGCGCCGCCCGAAGGC
	CCCAGCCACCCGCGAGAGCCAAGCACACCCCACCGCTACCGCGAGGGGCGGACCGAGCTGCGCAGGGA
	CAAGTCTCCTGGCCGCCCCCTGGAGCGAGAGAAGTCCCCCGGCCGGATGCTCAGCACGCGGAGAGAGC
	GGTCCCCCGGGAGGCTGTTTGAAGACAGCAGCAGGGGCCGGCTGCCTGCGGGAGCCGTGAGGACCCCG
	CTGTCCCAGGTGAACAAGGTGTGGGACCAGTCTTCAGTATAAATCTCAGCCAGAAAAACCAACTCCTC
	A
	ORF Start: ATG at 1		ORF Stop: TAA at 6160
	SEQ ID NO: 2	2053 aa	MW at 234700.1 kD
NOV1a,	MLKFKYGARNPLDAGAAEPIASRASRLNLFFQGKPPFMTQQQMSPLSREGILDALFVLFEECSQPALM
CG106764-01
Protein	KIKHVSNFVRKCSDTIAELQELQPSAKDFEVRSLVGCGHFAEVQVVREKATGDIYAMKVMKKKALLAQ
Sequence
	EQVSFFEEERNILSRSTSPWIPQLQYAFQDKNHLYLVMEYQPGGDLLSLLNRYEDQLDENLIQFYLAE
	LILAVHSVHLMGYVHRDIKPENILVDRTGHIKLVDFGSAAKMNSNKVNAKLPIGTPDYMAPEVLTVMN
	GDGKGTYGLDCDWWSVGVIAYEMIYGRSPFAEGTSARTFNNIMNFQRFLKFPDDPKVSSDFLDLIQSL
	LCGQKERLKFEGLCCHPFFSKIDWNNIRNAPPPFVPTLKSDDDTSNFDEPEKNSWVSSSPCQLSPSGF
	SGEELPFVGFSYSKALGILGRSESVVSGLDSPAKTSSMEKKLLIKSKELQDSQDKCHKMEQEMTRLHR
	RVSEVEAVLSQKEVELKASETQRSLLEQDLATYITECSSLKRSLEQARMEVSQEDDKALQLLHDIREQ
	SRKLQEIKEQEYQAQVEEMRLMMNQLEEDLVSARRRSDLYESELRESRLAAEEFKRKATECQHKLLKA
	KDQGKPEVGEYAKLEKINAEQQLKIQELQEKLEKAVKASTEATELLQNIRQAKERAERELEKLQNRED
	SSEGIRKKLVEAEERRHSLENKVKRLETMERRENRLKDDIOTKSOOIOOMADKILELEEKHREAOVSA
	QHLEVHLKQKEQHYEEKIKVLDNQIKKDLADKETLENMMQRHEEEAHEKGKILSEQKAMINAMDSKIR
	SLEQRIVELSEANKLAANSSLFTQRNMKAQEEMISELRQQKFYLETQAGKLEAQNRKLEEQLEKISHQ
	DHSDKNRLLELETRLREVSLEHEEQKLELKRQLTELQLSLQERESQLTALQAARAALESQLRQAKTEL
	EETTAEAEEEIQALTAHRDEIQRKFDALRNSCTVITDLEEQLNQLTEDNAELNNQNFYLSKQLDEASG
	ANDEIVQLRSEVDHLRREITEREMQLTSQKQTMEALKTTCTMLEEQVMDLEALNDELLEKERQWEAWR
	SVLGDEKSQFECRVRELQRMLDTEKQSRARADQRITESRQVVELAVKEHKAEILALQQALKEQKLKAE
	SLSDKLNDLEKKHAMLEMNARSLQQKLETERELKQRLLEEQAKLQQQMDLQKNHIFRLTQGLQEALDR
	ADLLKTERSDLEYQLENIQVLYSHEKVKMEGTISQQTKLIDFLQAKMDQPAKKKKVPLQYNELKLALE
	KEKARCAELEEALQKTRIELRSAREEAAHRKATDHPHPSTPATARQQIAMSAIVRSPEHQPSAMSLLA
	PPSSRRKESSTPEEFSRRLKERMHHNIPHRFNVGLNMRATKCAVCLDTVHFGRQASKCLECQVMCHPK
	CSTCLPATCGLPAEYATHFTEAFCRDKMNSPGLQTKEPSSSLHLEGWMKVPRNNKRGQQGWDRKYIVL
	EGSKVLIYDNEAREAGQRPVEEFELCLPDGDVSIHGAVGASELANTAKADVPYILKMESHPHTTCWPG
	RTLYLLAPSFPDKQRWVTALESVVAGGRVSREKAEADAKLLGNSLLKLEGDDRLDMNCTLPFSDQVVL
	VGTEEGLYALNVLKNSLTHVPGIGAVFQIYIIKDLEKLLMIAGEERALCLVDVKKVKQSLAQSHLPAQ
	PDISPNIFEAVKGCHLFGAGKIENGLCICAAMPSKVVILRYNENLSKYCIRKEIETSEPCSCIHFTNY
	SILIGTNKFYEIDMKQYTLEEFLDKNDHSLAPAVFAASSNSFPVSIVQVNSAGQREEYLLCFHEFGVF
	VDSYGRRSRTDDLKWSRLPLAFAYREPYLFVTHFNSLEVIEIQARSSAGTPARAYLDIPNPRYLGPAI
	SSGAIYLASSYQDKLRVICCKGNLVKESGTEHHRGPSTSRSSPNKRGPPTYNEHITKRVASSPAPPEG
	PSHPREPSTPHRYREGRTELRRDKSPGRPLEREKSPGRMLSTRRERSPGRLFEDSSRGRLPAGAVRTP
	LSQVNKVWDQSSV
	SEQ ID NO: 3	1870 bp
NOV1b,	CACCGGTACCACCATGTTGAAGTTCAAATATGGAGCGCGGAATCCTTTGGATGCTGGTGCTGCTGAA
268667493
DNA Sequence	CCCATTGCCAGCCGGGCCTCCAGGCTGAATCTGTTCTTCCAGGGGAAACCACCCTTTATGACTCAAC
	AGCAGATGTCTCCTCTTTCCCGAGAAGGGATATTAGATGCCCTCTTTGTTCTCTTTGAAGAATGCAG
	TCAGCCTGCTCTGATGAAGATTAAGCACGTGAGCAACTTTGTCCGGAAGTATTCCGACACCATGACT
	GAGTTACAGGAGCTCCAGCCTTCGGCAAAGGACTTCGAAGTCAGAAGTCTTGTAGGTTGTGGTCACT
	TTGCTGAAGTGCAGGTGGTAAGAGAGAAAGCAACCGGGGACATCTATGCTATGAAAGTGATGAAGAA
	GAAGGCTTTATTGGCCCAGGAGCAGGTTTCATTTTTTGAGGAAGAGCGGAACATATTATCTCGAAGC
	ACAAGCCCGTGGATCCCCCAATTACAGTATGCCTTTCAGGACAAAAATCACCTTTATCTGGTCATGG
	AATATCAGCCTGGAGGGGACTTGCTGTCACTTTTGAATAGATATGAGGACCAGTTAGATGAAAACCT
	GATACAGTTTTACCTAGCTGAGCTGATTTTGGCTGTTCACAGCGTTCATCTGATGGGATACGTGCAT
	CGAGACATCAAGCCTGAGAACATTCTCGTTGACCGCACAGGACACATCAAGCTGGTGGATTTTGGAT
	CTGCCGCGAAAATGAATTCAAACAAGATGGTGAATGCCAAACTCCCGATTGGGACCCCAGATTACAT
	GGCTCCTGAAGTGCTGACTGTGATGAACGGGGATGGAAAAGGCACCTACGGCCTGGACTGTGACTGG
	TGGTCAGTGGGCGTGATTGCCTATGAGATGATTTATGGGAGATCCCCCTTCGCAGAGGGAACCTCTG
	CCAGAACCTTCAATAACATTATGAATTTCCAGCGGTTTTTGAAATTTCCAGATGACCCCAAAGTGAG
	CAGTGACTTTCTTGATCTGATTCAAAGCTTGTTGTGCGGCCAGAAAGAGAGACTGAAGTTTGAAGGT
	CTTTGCTGCCATCCTTTCTTCTCTAAAATTGACTGGAACAACATTCGTAACTCTCCTCCCCCCTTCG
	TTCCCACCCTCAAGTCTGACGATGACACCTCCAATTTTGATGAACCAGAGAAGAATTCGTGGGTTTC
	ATCCTCTCCGTGCCAGCTGAGCCCCTCAGGCTTCTCGGGTGAAGAACTGCCGTTTGTGGGGTTTTCG
	TACAGCAAGGCACTGGGGATTCTTGGTAGATCTGAGTCTGTTGTGTCGGGTCTGGACTCCCCTGCCA
	AGACTAGCTCCATGGAAAAGAAACTTCTCATCAAAAGCAAAGAGCTACAAGACTCTCAGGACAAGTG
	TCACAAGATGGAGCAGGAAATGACCCGGTTACATCGGAGAGTGTCAGAGGTGGAGGCTGTGCTTAGT
	CAGAAGGAGGTGGAGCTGAAGGCCTCTGAGACTCAGAGATCCCTCCTGGAGCAGGACCTTGCTACCT
	ACATCACAGAATGCAGTAGCTTAAAGCGAAGTTTGGAGCAAGCACGGATGGAGGTGTCCCAGGAGGA
	TGACAAAGCACTGCAGCTTCTCCATGATATCAGAGAGCAGAGCCGGAAGCTCCAAGAAATCAAAGAG
	CAGGAGTACCAGGCTCAAGTGGAAGAAATGAGGTTGATGATGAATCAGTTGGAAGAGGATCTTGTCT
	CAGCAAGAAGACGGAGTGATCTCTACGAATCTGAGCTGAGAGAGTCTCGGCTTGCTGCTGAAGAATT
	CAAGCGGAAAGCGACAGAATGTCAGCATAAACTGTTGAAGGCTAAGGATCAGGTCGACGGC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO: 4	623 aa	MW at 70970.0 kD
NOV1b,	TGTTMLKFKYGARNPLDAGAAEPIASRASRLNLFFQGKPPFMTQQQMSPLSREGILDALFVLFEECS
268667493
Protein	QPALMKIKHVSNFVRKYSDTIAELQELQPSAKDFEVRSLVGCGHFAEVQVVREKATGDIYAMKVMKK
Sequence
	KALLAQEQVSFFEEERNILSRSTSPWIPQLQYAFQDKNHLYLVMEYQPGGDLLSLLNRYEDQLDENL
	IQFYLAELILAVHSVHLMGYVHRDIKPENILVDRTGHIKLVDFGSAAKMNSNKMVNAKLPIGTPDYM
	APEVLTVMNGDGKGTYGLDCDWWSVGVIAYEMIYGRSPFAEGTSARTFNNIMNFQRFLKFPDDPKVS
	SDFLDLIQSLLCGQKERLKFEGLCCHPFFSKIDWNNIRNSPPPFVPTLKSDDDTSNFDEPEKNSWVS
	SSPCQLSPSGFSGEELPFVGFSYSKALGILGRSESVVSGLDSPAKTSSMEKKLLIKSKELQDSQDKC
	HKMEOEMTRLHRRVSEVEAVLSOKEVELKASETORSLLEODLATYITECSSLKRSLEOARMEVSOED
	DKALQLLHDIREQSRKLQEIKEQEYQAQVEEMRLMMNQLEEDLVSARRRSDLYESELRESRLAAEEF
	KRKATECQHKLLKAKDQVDG
	SEQ ID NO: 5	2497 bp
NOV1c,	CACCGGTACCCAGGGGAAGCCTGAAGTGGGAGAATATGCGAAACTGGAGAAGATCAATGCTGAGCAGC
268667539
DNA Sequence	AGCTCAAAATTCAGGAGCTCCAAGAGAAACTGGAGAAGGCTGTAAAAGCCAGCACGGAGGCCACCGAG
	CTGCTGCAGAATATCCGCCAGGCAAAGGAGCGAGCCGAGAGGGAGCTGGAGAAGCTGCAGAACCGAGA
	GGATTCTTCTGAAGGCATCAGAAAGAAGCTGGTGGAAGCTGAGGAACGCCGCCATTCTCTGGAGAACA
	AGGTAAAGAGACTAGAGACCATGGAGCGTAGAGAAAACAGACTGAAGGATGACATCCAGACAAAATCC
	CAACAGATCCAGCAGATGGCTGATAAAATTCTGGAGCTCGAAGAGAAACATCGGGAGGCCCAAGTCTC
	AGCCCAGCACCTAGAAGTGCACCTGAAACAGAAAGAGCAGCACTATGAGGAAAAGATTAAAGTGTTGG
	ACAATCAGATAAAGAAAGACCTGGCTGACAAGGAGACACTGGAGAACATGATGCAGAGACACGAGGAG
	GAGGCCCATGAGAAGGGCAAAATTCTCAGCGAACAGAAGGCGATGATCAATGCTATGGATTCCAAGAT
	CAGATCCCTGGAACAGAGGATTGTGGAACTGTCTGAAGCCAATAAACTTGCAGCAAATAGCAGTCTTT
	TTACCCAAAGGAACATGAAGGCCCAAGAAGAGATGATTTCTGAACTCAGGCAACAGAAATTTTACCTG
	GAGACACAGGCTGGGAAGTTGGAGGCCCAGAACCGAAAACTGGAGGAGCAGCTGGAGAAGATCAGCCA
	CCAAGACCACAGTGACAAGAATCGGCTGCTGGAACTGGAGACAAGATTGCGGGAGGTCAGTCTAGAGC
	ACGAGGAGCAGAAACTGGAGCTCAAGCGCCAGCTCACAGAGCTACAGCTCTCCCTGCAGGAGCGCGAG
	TCACAGTTGACAGCCCTGCAGGCTGCACGGGCGGCCCTGGAGAGCCAGCTTCGCCAGGCGAAGACAGA
	GCTGGAAGAGACCACAGCAGAAGCTGAAGAGGAGATCCAGGCACTCACGGCACATAGAGATGAAATCC
	AGCGCAAATTTGATGCTCTTCGTAACAGCTGTACTGTAATCACAGACCTGGAGGAGCAGCTAAACCAG
	CTGACCGAGGACAACGCTGAACTCAACAACCAAAACTTCTACTTGTCCAAACAACTCGATGAGGCTTC
	TGGCGCCAACGACGAGATTGTACAACTGCGAAGTGAAGTGGACCATCTCCGCCGGGAGATCACGGAAC
	GAGAGATGCAGCTTACCAGCCAGAAGCAAACGATGGAGGCTCTGAAGACCACGTGCACCATGCTGGAG
	GAACAGGTCATGGATTTGGAGGCCCTAAACGATGATCTGCTAGAAAAAGAGCGGCAGTGGGAGGCCTG
	GAGGAGCGTCCTGGGTGATGAGAAATCCCAGTTTGAGTGTCGGGTTCGAGAGCTGCAGAGAATGCTGG
	ACACCGAGAAACAGAGCAGGGCGAGAGCCGATCAGCGGATCACCGAGTCTCGCCAGGTGGTGGAGCTG
	GCAGTGAAGGAGCACAAGGCTGAGATTCTCGCTCTGCAGCAGGCTCTCAAAGAGCAGAAGCTGAAGGC
	CGAGAGCCTCTCTGACAAGCTCAATGACCTGGAGAAGAAGCATGCTATGCTTGAAATGAATGCCCGAA
	GCTTACAGCAGAAGCTGGAGACTGAACGAGAGCTCAAACAGAGGCTTCTGGAAGAGCAAGCCAAATTA
	CAGCAGCAGATGGACCTGCAGAAAAATCACATTTTCCGTCTGACTCAAGGACTGCAAGAAGCTCTAGA
	TCGGGCTGATCTACTGAAGACAGAAAGAAGTGACTTGGAGTATCAGCTGGAAAACATTCAGGTTCTCT
	ATTCTCATGAAAAGGTGAAAATGGAAGGCACTATTTCTCAACAAACCAAACTCATTGATTTTCTGCAA
	GCCAAAATGGACCAACCTGCTAAAAAGAAAAAGGTTCCTCTGCAGTACAATGAGCTGAAGCTGGCCCT
	GGAGAAGGAGAAAGCTCGCTGTGCAGAGCTAGAGGAAGCCCTTCAGAAGACCCGCATCGAGCTCCGGT
	CCGCCCGGGAGGAAGCTGCCCACCGCAAAGCAACGGACCACCCACACCCATCCACGCCAGCCACCGCG
	AGGCAGCAGATCGCCATGTCCGCCATCGTGCGGTCGCCAGAGCACCAGCCCAGTGCCATGAGCCTGCT
	GCATGCACCACAATATTCCTCACCGATTCAACGTAGGACTGAACATGCGAGCCACAAAGTGTGCTGTG
	TGTCTGGATACCGTGCACTTTGGACGCCAGGCATCCAAATGTCTCGAATGTCAGGTGATGTGTCACCC
	CAAGTGCTCCACGTGCTTGCCAGCCACCTGCGGCTTGCCTGTCGACGGC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO: 6	832 aa	MW at 96885.8 kD
NOV1c	TGTQGKPEVGEYAKLEKINAEQQLKIQELQEKLEKAVKASTEATELLQNIRQAKERAERELEKLQNRE
268667539
Protein	DSSEGIRKKLVEAEERRHSLENKVKRLETMERRENRLKDDIQTKSQQIQQMADKILELEEKHREAQVS
Sequence
	AQHLEVHLKQKEQHYEEKIKVLDNQIKKDLADKETLENMMQRHEEEAHEKGKILSEQKAMINAMDSKI
	RSLEQRIVELSEANKLAANSSLFTQRNMKAQEEMISELRQQKFYLETQAGKLEAQNRKLEEQLEKISH
	QDHSDKNRLLELETRLREVSLEHEEQKLELKRQLTELQLSLQERESQLTALQAARAALESQLRQAKTE
	LEETTAEAEEEIQALTAHRDEIQRKFDALRNSCTVITDLEEQLNQLTEDNAELNNQNFYLSKQLDEAS
	GANDEIVQLRSEVDHLRREITEREMQLTSQKQTMEALKTTCTMLEEQVMDLEALNDELLEKERQWEAW
	RSVLGDEKSQFECRVRELQRMLDTEKQSRARADQRITESRQVVELAVKEHKAEILALQQALKEQKLKA
	ESLSDKLNDLEKKHAMLEMNARSLQQKLETERELKQRLLEEQAKLQQQMDLQKNHIFRLTQGLQEALD
	RADLLKTERSDLEYQLENIQVLYSHEKVKMEGTISQQTKLIDFLQAKMDQPAKKKKVPLQYNELKLAL
	EKEKARCAELEEALQKTRIELRSAREEAAHRKATDHPHPSTPATARQQIAMSAIVRSPEHQPSAMSLL
	APPSSRRKESSTPEEFSRRLKERMHHNIPHRFNVGLNMRATKCAVCLDTVHFGRQASKCLECQVMCHP
	KCSTCLPATCGLPVDG
	SEQ ID NO 7	2542 bp
NOV1d,	CACCGGTACCCAGGGGAAGCCTGAAGTGGGAGAATATGCGAAACTGGAGAAGATCAATGCTGAGCAG
268667543
DNA Sequence	CAGCTCAAAATTCAGGAGCTCCAAGAGAAACTGCAGAAGGCTGTAAAAGCCACCACCGAGGCCACCG
	AGCTGCTGCACAATATCCGCCAGGCAAAGGAGCGAGCCGAGAGGGAGCTGGAGAAGCTGCAGAACCG
	AGAGGATTCTTCTGAAGGCATCAGAAAGAAGCTGCTGGAAGCTGAGGAACGCCGCCATTCTCTGGAG
	AACAAGGTAAAGAGACTAGAGACCATGGAGCCTAGAGAAAACAGACTGAACGATGACATCCAGACAA
	AATCCCAACAGATCCAGCAGATGGCTGATAAAATTCTGGACCTCGAAGAGAAACATCGGGAGGCCCA
	AGTCTCAGCCCAGCACCTAGAAGTGCACCTGAAACAGAAAGAGCAGCACTATGAGGAAAAGATTAAA
	GTGTTGGACAATCAGATAAACAAAGACCTGGCTGACAAGGAGACACTGGAGAACATGATGCAGAGAC
	ACGAGGAGGAGGCCCATGAGAAGGGCAAAATTCTCAGCGAACAGAAGGCGATGATCAATGCTATGGA
	TTCCAACATCAGATCCCTGGAACAGAGGATTGTGGAACTGTCTGAACCCAATAAACTTCCAGCAAAT
	AGCAGTCTTTTTACCCAAAGGAACATGAAGGCCCAAGAAGAGATGATTTCTGAACTCAGGCAACAGA
	AATTTTACCTGGAGACACAGGCTGGGAAGTTGGAGGCCCAGAACCGAAAACTGGAGGAGCAGCTGGA
	GAAGATCAGCCACCAAGACCACAGTGACAAGAATCGGCTGCTGGAACTGGAGACAAGATTGCGGGAG
	GTCAGTCTAGAGCACGAGGAGCAGAAACTGGAGCTCAAGCGCCAGCTCACAGAGCTACAGCTCTCCC
	TGCAGGAGCGCGAGTCACAGTTGACAGCCCTGCAGGCTGCACGGGCGGCCCTGGAGAGCCAGCTTCG
	CCAGGCGAAGACAGAGCTGGAAGAGACCACAGCAGAAGCTGAAGAGGAGATCCAGGCACTCACGGCA
	CATAGAGATGAAATCCAGCGCAAATTTGATGCTCTTCGTAACAGCTGTACTGTAATCACAGACCTGG
	AGGAGCAGCTAAACCAGCTGACCGAGGACAACGCTGAACTCAACAACCAAAACTTCTACTTGTCCAA
	ACAACTCGATGAGGCTTCTGGCGCCAACGACGAGATTGTACAACTGCGAAGTGAAGTGGACCATCTC
	CGCCGGGAGATCACGGAACGAGAGATGCAGCTTACCAGCCAGAAGCAAACGATGGAGGCTCTGAAGA
	CCACGTGCACCATGCTGGAGGAACAGGTCATGGATTTGGAGGCCCTAAACGATGAGCTGCTAGAAAA
	AGAGCGGCAGTGGGAGGCCTGGAGGAGCGTCCTGGGTGATGAGAAATCCCAGTTTGAGTGTCGGGTT
	CGAGAGCTGCAGAGGATGCTGGACACCGAGAAACAGAGCAGGGCGAGAGCCGATCAGCGGATCACCG
	AGTCTCGCCAGGTGGTGGAGCTGGCAGTGAAGGAGCACAAGGCTGAGATTCTCGCTCTGCAGCAGGC
	TCTCAAAGAGCAGAAGCTGAAGGCCGAGAGCCTCTCTGACAAGCTCAATGACCTGGAGAAGAAGCAT
	GCTATGCTTGAAATGAATGCCCGAAGCTTACAGCAGAAGCTGGAGACTGAACGAGAGCTCAAACAGA
	GGCTTCTGGAAGAGCAAGCCAAATTACAGCAGCAGATGGACCTGCAGAAAAATCACATTTTCCGTCT
	GACTCAAGGACTGCAAGAAGCTCTAGATCGGGCTGATCTACTGAAGACAGAAAGAAGTGACTTGGAG
	TATCAGCTGGAAAACATTCAGGTTCTCTATTCTCATGAAAAGGTGAAAATGGAAGGCACTATTTCTC
	AACAAACCAAACTCATTGATTTTCTGCAAGCCAAAATGGACCAACCTGCTAAAAAGAAAAAGGGTTT
	ATTTAGTCGACGGAAAGAGGACCCTGCTTTACCCACACAGGTTCCTCTGCAGTACAATGAGCTGAAG
	CTGGCCCTGGAGAAGGAGAAAGCTCGCTGTGCAGAGCTAGAGGAAGCCCTTCAGAAGACCCGCATCG
	AGCTCCGGTCCGCCCGGGAGGAAGCTGCCCACCGCAAAGCAACGGACCACCCACACCCATCCACGCC
	AGCCACCGCGAGGCAGCAGATCGCCATGTCTGCCATCGTGCGGTCGCCAGAGCACCAGCCCAGTGCC
	ATGAGCCTGCTGGCCCCGCCATCCAGCCGCAGAAAGGAGTCTTCAACTCCAGAGGAATTTAGTCGGC
	GTCTTAAGGAACGCATGCACCACAATATTCCTCACCGATTCAACGTAGGACTGAACATGCGAGCCAC
	AAAGTGTGCTGTYGTGTCTGGATACCGTGCACTTTGGACGCCAGGATCCAAATGTCTCGAATGTCAG
	GTGATGTGTCACCCCAAGTGCTCCACGTGCTTGCCAGCCACCTGCGGCTTGCCTGTCGACGGC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO: 8	847 aa	MW at 98582.7 kD
NOV1d	TGTQGKPEVGEYAKLEKINAEQQLKIQELQEKLEKAVKASTEATELLQNIRQAKERAERELEKLQNR
268667543
Protein	EDSSEGIRKKLVEAEERRHSLENKVKRLETMERRENRLKDDIQTKSQQIQQMADKILELEEKHREAQ
Sequence
	VSAQHLEVHLKQKEQHYEEKIKVLDNQIKKDLADKETLENMMQRHEEEAHEKGKILSEQKAMINAMD
	SKIRSLEQRIVELSEANKLAANSSLFTQRNMKAQEEMISELRQQKFYLETQAGKLEAQNRKLEEQLE
	KISHQDHSDKNRLLELETRLREVELEHEEQKLELKRQLTELQLSLQERESQLTALQAARAALESQLR
	QAKTELEETTAEAEEEIQALTAHRDEIQRKFDALRNSCTVITDLEEQLNQLTEDNAELNNQNFYLSK
	QLDEASGANDEIVQLRSEVDHLRREITEREMQLTSQKQTMEALKTTCTMLEEQVMDLEALNDELLEK
	ERQWEAWRSVLGDEKSQFECRVRELQRMLDTEKQSRARADQRITESRQVVELAVKEHKAEILALQQA
	LKEQKLKAESLSDKLNDLEKKHAMLEMNARSLQQKLETERELKQRLLEEQAKLQQQMDLQKNHIFRL
	TQGLQEALDRADLLKTERSDLEYQLENIQVLYSHEKVKMEGTISQQTKLIDFLQAKMDQPAKKKKGL
	FSRRKEDPALPTQVPLQYNELKLALEKEKARCAELEEALQKTRIELRSAREEAAHRKATDHPHPSTP
	ATARQQIAMSAIVRSPEHQPSAMSLLAPPSSRRKESSTPEEFSRRLKERMHHNIPHRFNVGLNMRAT
	KCAVCLDTVHFGRQASKCLECQVMCHPKCSTCLPATCGLPVDG
	SEQ ID NO: 9	1870 bp
NOV1e,	CACCGGTACCTGCGGCTTGCCTGCTGAATATGCCACACACTTCACCGAGGCCTTCTGCCGTGACAAAA
268667555
DNA Sequence	TGAACTCCCCAGGTCTCCAGACCAAGGAGCCCAGCAGCAGCTTGCACCTGGAAGGGTGGATGAAGGTG
	CCCAGGAATAACAAACGAGGACAGCAAGGCTGGGACAGGAAGTACATTGTCCTGGAGGGATCAAAAGT
	CCTCATTTATGACAATGAAGCCAGAGAAGCTGGACAGAGGCCGGTGGAAGAATTTGAGCTGTGCCTTC
	CCGACGGGGATGTATCTATTCATGGTGCCGTTGGTGCTTCCGAACTCGCAAATACAGCCAAAGCAGAT
	GTCCCATACATACTGAAGATGGAATCTCACCCGCACACCACCTGCTGGCCCGGGAGAACCCTCTACTT
	GCTAGCTCCCAGCTTCCCTGACAAACAGCGCTGGGTCACCGCCTTAGAATCAGTTGTCGCAGGTGGGA
	GAGTTTCTAGGGAAAAAGCAGAAGCTGATGCTAAACTGCTTGGAAACTCCCTGCTGAAACTGGAAGGT
	GATGACCGTCTAGACATGAACTGCACGCTGCCCTTCAGTGACCAGGTGGTGTTGGTGGGTACCGAGGA
	AGGGCTCTACGCCCTGAATGTCTTGAAAAACTCCCTAACCCATGTCCCAGGAATTGGAGCAGTCTTCC
	AAATTTATATTATCAAGGACCTGGAGAAGCTACTCATGATAGCAGGAGAAGAGCGGGCACTGTGTCTT
	GTGGACGTGAAGAAAGTGAAACAGTCCCTGGCCCAGTCCCACCTGCCTGCCCAGCCCGACATCTCACC
	CAACATTTTTGAAGCTGTCAAGGGCTGCCACTTGTTTGGGGCAGGCAAGATTGAGAACGGGCTCTGCA
	TCTGTGCAGCCATGCCCAGCAAAGTCGTCATTCTCCGCTACAACGAAAACCTCAGCAAATACTGCATC
	CGGAAAGAGATAGAGACCTCAGAGCCCTGCAGCTGTATCCACTTCACCAATTACAGTATCCTCATTGG
	AACCAATAAATTCTACGAAATCGACATGAAGCAGTACACGCTCGAGGAATTCCTGGATAAGAATGACC
	ATTCCTTGGCACCTGCTGTGTTTGCCGCCTCTTCCAACAGCTTCCCTGTCTCAATCGTGCAGGTGAAC
	AGCGCAGGGCAGCGAGAGGAGTACTTGCTGTGTTTCCACGAATTTGGAGTGTTCGTGGATTCTTACGG
	AAGACGTAGCCGCACAGACGATCTCAAGTGGAGTCGCTTACCTTTGGCCTTTGCCTACAGAGAACCCT
	ATCTGTTTGTGACCCACTTCAACTCACTCGAAGTAATTGAGATCCAGGCACGCTCCTCAGCAGGGACC
	CCTGCCCGAGCGTACCTGGACATCCCGAACCCGCGCTACCTGGGCCCTGCCATTTCCTCAGGAGCGAT
	TTACTTGGCGTCCTCATACCAGGATAAATTAAGGGTCATTTGCTGCAAGGGAAACCTCGTGAAGGAGT
	CCGGCACTGAACACCACCGGGGCCCGTCCACCTCCCGCAGCAGCCCCAACAAGCGAGGCCCACCCACG
	TACAACGAGCACATCACCAAGCGCGTGGCCTCCAGCCCAGCGCCGCCCGCAAGGCCCAGCCACCCGCG
	AGAGCCAAGCACACCCCACCGCTACCGCGAGGGGCGGACCGAGCTGCGCAGGGACAAGTCTCCTGGCC
	GCCCCCTGGAGCGAGAGAAGTCCCCCGGCCGGATGCTCAGCACGCGGAGAGAGCGGTCCCCCGGGAGG
	CTGTTTGAAGACAGCAGCAGGGGCCGGCTGCCTGCGGGAGCCGTGAGGACCCCGCTGTCCCAGGTGAA
	CAAGGTGTGGGACCAGTCTTCAGTAGTCGACGGC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO: 10	623 aa	MW at 69278.9 kD
NOV1e,	TGTCGLPAEYATHFTEAFCRDKMNSPGLQTKEPSSSLHLEGWMKVPRNNKRGQQGWDRKYIVLEGSKV
268667555
Protein	LIYDNEAREAGQRPVEEFELCLPDGDVSIHGAVGASELANTAKADVPYILKMESHPHTTCWPGRTLYL
Sequence
	LAPSFPDKQRWVTALESVVVAGGRVSREKAEDAKLLGNSLLKLEGDDRLDMNCTLPFSDQVVLVGTEE
	GLYALNVLKNSLTHVPGIGAVFQIYIIKDLEKLLMIAGEERALCLVDVKKVKQSLAQSHLPAQPDISP
	NIFEAVKGCHLFGAGKIENGLCICAAMPSKVVILRYNENLSKYCIRKEIETSEPCSCIHFTNYSILIG
	TNKFYEIDMKQYTLEEFLDKNDHSLAPAVFAASSNSFPVSIVQVNSAGQREEYLLCFHEFGVFVDSYG
	RRSRTDDLKWSRLPLAFAYREPYLFVTHFNSLEVIEIQARSSAGTPARAYLDIPNPRYLGPAISSGAI
	YLASSYQDKLRVICCKGNLVKESGTEHHRGPSTSRSSPNKRGPPTYNEHITKRVASSPAPPEGPSHPR
	EPSTPHRYREGRTELRRDKSPGRPLEREKSPGRMLSTRRERSPGRLFEDSSRGRLPAGAVRTPLSQVN
	KVWDQSSVVDG
	SEQ ID NO: 11	1915 bp
NOV1f,	CACCGGTACCTGCGGCTTGCCTGCTGAATATGCCACACACTTCACCGAGGCCTTCTGCCGTGATAAAA
268667574
DNA Sequence	TGAACTCCCCAGGTCTCCAGACCAAGGAGCCCAGCAGCAGCTTGCACCTGGAAGGGTGGATGAAGGTG
	CCCAGGAATAACAAACGAGGACAGCAAGGCTGGGACAGGAAGTACATTGTCCTGGAGGGATCAAAAGT
	CCTCATTTATGACAATGAAGCCAGAGAAGCTGGACAGAGGCCGGTGGAAGAATTTGAGCTGTGCCTTC
	CCGACGGGGATGTATCTATTCATGGTGCCGTTGGTGCTTCCGAACTCGCAAATACAGCCAAAGCAGAT
	GTCCCATACATACTGAAGATGGAATCTCACCCGCACACCACCTGCTGGCCCGGGAGAACCCTCTACTT
	GCTAGCTCCCAGCTTCCCTGACAAACAGCGCTGGGTCACCGCCTTAGAATCAGTTGTCGCAGGTGGGA
	GAGTTTCTAGGGAAAAAGCAGAAGCTGATGCTGCCCGCGACTGTGTTTCTTACGAGCTTCTGCCTGCC
	TGGGTTCAGAAACTGCTTGGAAACTCCCTGCTGAAACTGGAAGGTGATGACCGTCTAGACATGAACTG
	CACACTGCCCTTCAGTGACCAGGTGGTGTTGGTGGGCACCGAGGAAGGGCTCTACGCCCTGAATGTCT
	TGAAAAACTCCCTAACCCATGTCCCAGGAATTGGAGCAGTCTTCCAAATTTATATTATCAAGGACCTG
	GAGAAGCTACTCATGATAGCAGGAGAAGAGCGGGCACTGTGTCTTGTGGACGTGAAGAAAGTGAAACA
	GTCCCTGGCCCAGTCCCACCTGCCTGCCCAGCCCGACATCTCACCCAACATTTTTGAAGCTGTCAAGG
	GCTGCCACTTGTTTGGGGCAGGCAAGATTGAGAACGGGCTCTGCATCTGTGCAGCCATGCCCAGCAAA
	GTCGTCATTCTCCGCTACAACGAAAACCTCAGCAAATACTGCATCCGGAAAGAGATAGAGACCTCAGA
	GCCCTGCAGCTGTATCCACTTCACCAATTACAGTATCCTCATTGGAACCAATAAATTCTACGAAATCG
	ACATGAAGCAGTACACGCTCGAGGAATTCCTGGATAAGAATGACCATTCCTTGGCACCTGCTGTGTTT
	GCCGCCTCTTCCAACAGCTTCCCTGTCTCAATCGTGCAGGTGAACAGCGCAGGGCAGCGAGAGGAGTA
	GTTGCTGTGTTTCCACGAATTTGGAGTGTTCGTGGATTCTTACGGAAGACGTAGCCGCACAGACGATC
	TCAAGTGGAGTCGCTTACCTTTGGCCTTTGCCTACAGAGAACCCTATCTGTTTGTGACCCACTTCAAC
	TCACTCGAAGTAATTGAGATCCAGGCACGCTCCTCAGCAGGGACCCCTGCCCGAGCGTACCTGGACAT
	CCCGAACCCGCGCTACCTGGGCCCTGCCATTTCCTCAGGAGCGATTTACTTGGCGTCCTCATACCAGG
	ATAAATTAAGGGTCATTTGCTGCAAGGGAAACCTCGTGAAGGAGTCCGGCACTGAACACCACCGGGGC
	CCGTCCACCTCCCGCAGCAGCCCCAACAAGCGAGGCCCACCCACGTACAACGAGCACATCACCAAGCG
	CGTGGCCTCCAGCCCAGCGCCGCCCGAAGGCCCCAGCCACCCGCGAGAGCCAAGCACACCCCACCGCT
	ACCGCGAGGGGCGGACCGAGCTGCGAGGGACAAGTCTCCTGGCCGCCCCCCTGGAGCGAGAGAAGTCC
	CCCGGCCGGATGCTCAGCACGCGGAGAGAGCGGTCCCCCGGGAGGCTGTTTGAAGACAGCAGCAGGGG
	CCGGCTGCCTGCGGGAGCCGTGAGGACCCCGCTGTCCCAGGTGAACAAGGTGTGGGACCAGTCTTCAG
	TAGTCGACGGC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO: 12	638 aa	MW at 71010.8 kD
NOV1f,	TGTCGLPAEYATHFTEAFCRDKMNSPGLQTKEPSSSLHLEGWMKVPRNNKRGQQGWDRKYIVLEGSKV
268667574
Protein	LIYDNEAREAGQRPVEEFELCLPDGDVSIHGAVGASELANTAKADVPYILKMESHPHTTCWPGRTLYL
Sequence
	LAPSFPDKQRWVTALESVVAGGRVSREKAEADAARDCVSYELLPAWVQKLLGNSLLKLEGDDRLDMNC
	TLPFSDQVVLVGTEEGLYALNVLKNSLTHVPGIGAVFQIYIIKDLEKLLMIAGEERALCLVDVKKVKQ
	SLAQSHLPAQPDISPNIFEAVKGCHLFGAGKIENGLCICAAMPSKVVILRYNENLSKYCIRKEIETSE
	PCSCIHFTNYSILIGTNKFYEIDMKQYTLEEFLDKNDHSLAPAVFAASSNSFPVSIVQVNSAGQREEY
	LLCFHEFGVFVDSYGRRSRTDDLKWSRLPLAFAYREPYLFVTHFNSLEVIEIQARSSAGTPARAYLDI
	PNPRYLGPAISSGAIYLASSYQDKLRVICCKGNLVKESGTEHHRGPSTSRSSPNKRGPPTYNEHITKR
	VASSPAPPEGPSHPREPSTPHRYREGRTELRRDKSPGRPLEREKSPGRMLSTRRERSPGRLFEDSSRG
	RLPAGAVRTPLSQVNKVWDQSSVVDG
SEQ ID NO: 13	6201 bp
NOV1g,	ATGTTGAAGTTCAAATATGGAGCGCGGAATCCTTTGGATGCTGGTGCTGCTGAACCCATTGCCAGCC
CG106764-02
DNA Sequence	GGGCCTCCAGGCTGAATCTGTTCTTCCAGGGGAAACCACCCTTTATGACTCAACAGCAGATGTCTCC
	TCTTTCCCGAGAAGGGATATTAGATGCCCTCTTTGTTCTCTTTGAAGAATGCAGTCAGCCTGCTCTG
	ATGAAGATTAAGCACGTGAGCAACTTTGTCCGGAAGTGTTCCGACACCATAGCTGAGTTACAGGAGC
	TCCAGCCTTCGGCAAAGGACTTCGAAGTCAGAAGTCTTGTAGGTTGTGGTCACTTTGCTGAAGTGCA
	GGTGGTAAGAGAGAAAGCAACCGGGGACATCTATGCTATGAAAGTGATGAAGAAGAAGGCTTTATTG
	GCCCAGGAGCAGGTTTCATTTTTTGAGGAAGAGCGGAACATATTATCTCGAAGCACAAGCCCGTGGA
	TCCCCCAATTACAGTATGCCTTTCAGGACAAAAATCACCTTTATCTGGTGATGGAATATCAGCCTGG
	AGGGGACTTGCTGTCACTTTTGAATAGATATGAGGACCAGTTAGATGAAAACCTGATACAGTTTTAC
	CTAGCTGAGCTGATTTTGGCTGTTCACAGCGTTCATCTGATGGGATACGTGCATCGGGACATCAAGC
	CTGAGAACATTCTCGTTGACCGCACAGGACACATCAAGCTGGTGGATTTTGGATCTGCCGCGAAAAT
	GAATTCAAACAAGGTGAATGCCAAACTCCCGATTGGGACCCCAGATTACATGGCTCCTGAAGTGCTG
	ACTGTGATGAACGGGGATGGAAAAGGCACCTACGGCCTGGACTGTGACTGGTGGTCAGTGGGCGTGA
	TTGCCTATGAGATGATTTATGGGAGATCCCCCTTCGCAGAGGGAACCTCTGCCAGAACCTTCAATAA
	CATTATGAATTTCCAGCGGTTTTTGAAATTTCCAGATGACCCCAAAGTGAGCAGTGACTTTCTTGAT
	CTGATTCAAAGCTTGTTGTGCGGCCAGAAAGAGAGACTGAAGTTTGAAGGTCTTTGCTGCCATCCTT
	TCTTCTCTAAAATTGACTGGAACAACATTCGTAACGCTCCTCCCCCCTTCGTTCCCACCCTCAAGTC
	TGACGATGACACCTCCAATTTTGATGAACCAGAGAAGAATTCGTGGGTTTCATCCTCTCCGTGCCAG
	CTGAGCCCCTCAGGCTTCTCGGGTGAAGAACTGCCGTTTGTGGGGTTTTCGTACAGCAAGGCACTGG
	GGATTCTTGGTAGATCTGAGTCTGTTGTGTCGGGTCTGGACTCCCCTGCCAAGACTAGCTCCATGGA
	AAAGAAACTTCTCATCAAAAGCAAAGAGCTACAAGACTCTCAGGACAAGTGTCACAAGATGGAGCAG
	GAAATGACCCGGTTACATCGGAGAGTGTCAGAGGTGGAGGCTGTGCTTAGTCAGAAGGAGGTGGAGC
	TGAAGGCCTCTGAGACTCAGAGATCCCTCCTGGAGCAGGACCTTGCTACCTACATCACAGAATGCAG
	TAGCTTAAAGCGAAGTTTGGAGCAAGCACGGATGGAGGTGTCCCAGGAGGATGACAAAGCACTGCAG
	CTTCTCCATGATATCAGAGAGCAGAGCCGGAAGCTCCAAGAAATCAAAGAGCAGGAGTACCAGGCTC
	AAGTGGAAGAAATGAGGTTGATGATGAATCAGTTGGAAGAGGATCTTGTCTCAGCAAGAAGACGGAG
	TGATCTCTACGAATCTGAGCTGAGAGAGTCTCGGCTTGCTGCTGAAGAATTCAAGCGGAAAGCGACA
	GAATGTCAGCATAAACTGTTGAAGGCTAAGGATCAGGGGAAGCCTGAAGTGGGAGAATATGCGAAAC
	TGGAGAAGATCAATGCTGAGCAGCAGCTCAAAATTCAGGAGCTCCAAGAGAAACTGGAGAAGGCTGT
	AAAAGCCAGCACGGAGGCCACCGAGCTGCTGCAGAATATCCGCCAGGCAAAGGAGCGAGCCGAGAGG
	GAGCTGGAGAAGCTGCAGAACCGAGAGGATTCTTCTGAAGGCATCAGAAAGAAGCTGGTGGAAGCTG
	AGGAACGCCGCCATTCTCTGGAGAACAAGGTAAAGAGACTAGAGACCATGGAGCGTAGAGAAAACAG
	ACTGAAGGATGACATCCAGACAAAATCCCAACAGATCCAGCAGATGGCTGATAAAATTCTGGAGCTC
	GAAGAGAAACATCGGGAGGCCCAAGTCTCAGCCCAGCACCTAGAAGTGCACCTGAAACAGAAAGAGC
	AGCACTATGAGGAAAAGATTAAAGTATTGGACAATCAGATAAAGAAAGACCTGGCTGACAAGGAGAC
	ACTGGAGAACATGATGCAGAGACACGAGGAGGAGGCCCATGAGAAGGGCAAAATTCTCAGCGAACAG
	AAGGCGATGATCAATGCTATGGATTCCAAGATCAGATCCCTGGAACAGAGGATTGTGGAACTGTCTG
	AAGCCAATAAACTTGCAGCAAATAGCAGTCTTTTTACCCAAAGGAACATGAAGGCCCAAGAAGAGAT
	GATTTCTGAACTCAGGCAACAGAAATTTTACCTGGAGACACAGGCTGGGAAGTTGGAGGCCCAGAAC
	CGAAAACTGGAGGAGCAGCTGGAGAAGATCAGCCACCAAGACCACAGTGACAAGAATCGGCTGCTGG
	AACTGGAGACAAGATTGCGGGAGGTGAGTCTAGAGCACGAGGAGCAGAAACTGGAGCTCAAGCGCCA
	GCTCACAGAGCTACAGCTCTCCCTGCAGGAGCGCGAGTCACAGTTGACAGCCCTGCAGGCTGCACGG
	GCGGCCCTGGAGAGCCAGCTTCGCCAGGCGAAGACAGAGCTGGAAGAGACCACAGCAGAAGCTGAAG
	AGGAGATCCAGGCACTCACGGCACATAGAGATGAAATCCAGCGCAAATTTGATGCTCTTCGTAACAG
	CTGTACTGTGATCACAGACCTGGAGGAGCAGCTAAACCAGCTGACCGAGGACAACGCTGAACTCAAC
	AACCAAAACTTCTACTTGTCCAAACAACTCGATGAGGCTTCTGGCGCCAACGACGAGATTGTACAAC
	TGCGAAGTGAAGTGGACCATCTCCGCCGGGAGATCACGGAACGAGAGATGCAGCTTACCAGCCAGAA
	GCAAACGATGGAGGCTCTGAAGACCACGTGCACCATGCTGGAGGAACAGGTCATGGATTTGGAGGCC
	CTAAACGATGAGCTGCTAGAAAAAGAGCGGCAGTGGGAGGCCTGGAGGAGCGTCCTGGGTGATGAGA
	AATCCCAGTTTGAGTGTCGGGTTCGAGAGCTGCAGAGGATGCTGGACACCGAGAAACAGAGCAGGGC
	GAGAGCCGATCAGCGGATCACCGAGTCTCGCCAGGTGGTGGAGCTGGCAGTGAAGGAGCACAAGGCT
	GAGATTCTCGCTCTGCAGCAGGCTCTCAAAGAGCAGAAGCTGAAGGCCGAGAGCCTCTCTGACAAGC
	TCAATGACCTGGAGAAGAAGCATGCTATGCTTGAAATGAATGCCCGAAGCTTACAGCAGAAGCTGGA
	GACTGAACGAGAGCTCAAACAGAGGCTTCTGGAAGAGCAAGCCAAATTACAGCAGCAGATGGACCTG
	CAGAAAAATCACATTTTCCGTCTGACTCAAGGACTGCAAGAAGCTCTAGATCGGGCTGATCTACTGA
	AGACAGAAAGAAGTGACTTGGAGTATCAGCTGGAAAACATTCAGGTGCTCTATTCTCATGAAAAGGT
	GAAAATGGAAGGCACTATTTCTCAACAAACCAAACTCATTGATTTTCTGCAAGCCAAAATGGACCAA
	CCTGCTAAAAAGAAAAAGGTGCCTCTGCAGTACAATGAGCTGAAGCTGGCCCTGGAGAAGGAGAAAG
	CTCGCTGTGCAGAGCTAGAGGAAGCCCTTCAGAAGACCCGCATCGAGCTCCGGTCCGCCCGGGAGGA
	AGCTGCCCACCGCAAAGCAACGGACCACCCACACCCATCCACGCCAGCCACCGCGAGGCAGCAGATC
	GCCATGTCTGCCATCGTGCGGTCGCCAGAGCACCAGCCCAGTGCCATGAGCCTGCTGGCCCCGCCAT
	CCAGCCGCAGAAAGGAGTCTTCAACTCCAGAGGAATTTAGTCGGCGTCTTAAGGAACGCATGCACCA
	CAATATTCCTCACCGATTCAACGTAGGACTGAACATGCGAGCCACAAAGTGTGCTGTGTGTCTGGAT
	ACCGTGCACTTTGGACGCCAGGCATCCAAATGTCTAGAATGTCAGGTGATGTGTCACCCCAAGTGCT
	CCACGTGCTTGCCAGCCACCTGCGGCTTGCCTGCTGAATATGCCACACACTTCACCGAGGCCTTCTG
	CCGTGACAAAATGAACTCCCCAGGTCTCCAGACCAAGGAGCCCAGCAGCAGCTTGCACCTGGAAGGG
	TGGATGAAGGTGCCCAGGAATAACAAACGAGGACAGCAAGGCTGGGACAGGAAGTACATTGTCCTGG
	AGGGATCAAAAGTCCTCATTTATGACAATGAAGCCAGAGAAGCTGGACAGAGGCCGGTGGAAGAATT
	TGAGCTGTGCCTTCCCGACGGGGATGTATCTATTCATGGTGCCGTTGGTGCTTCCGAACTCGCAAAT
	ACAGCCAAAGCAGATGTCCCATACATACTGAAGATGGAATCTCACCCGCACACCACCTGCTGGCCCG
	GGAGAACCCTCTACTTGCTAGCTCCCAGCTTCCCTGACAAACAGCGCTGGGTCACCGCCTTAGAATC
	AGTTGTCGCAGGTGGGAGAGTTTCTAGGGAAAAAGCAGAAGCTGATGCTAAACTGCTTGGAAACTCC
	CTGCTGAAACTGGAAGGTGATGACCGTCTAGACATGAACTGCACGCTGCCCTTCAGTGACCAGGTAG
	TGTTGGTGGGCACCGAGGAAGGGGCTCTACGCCTGGATGTCTTGAAAAACTCCCTAACCCATGTCCC
	AGGAATTGGAGCAGTCTTCCAAATTTATATTATCAAGGACCTGGAGAAGCTACTCATGATAGCAGGT
	GAAGAGCGGGCACTGTGTCTTGTGGACGTGAAGAAAGTGAAACAGTCCCTGGCCCAGTCCCACCTGC
	CTGCCCAGCCCGACATCTCACCCAACATTTTTGAAGCTGTCAAGGGCTGCCACTTGTTTGGGGCAGG
	CAAGATTGAGAACGGGCTCTGCATCTGTGCAGCCATGCCCAGCAAAGTCGTCATTCTCCGCTACAAC
	GAAAACCTCAGCAAATACTGCATCCGGAAAGAGATAGAGACCTCAGAGCCCTGCAGCTGTATCCACT
	TCACCAATTACAGTATCCTCATTGGAACCAATAAATTCTACGAAATCGACATGAAGCAGTACACGCT
	CGAGGAATTCCTGGATAAGAATGACCATTCCTTGGCACCTGCTGTGTTTGCCGCCTCTTCCAACAGC
	TTCCCTGTCTCAATCGTGCAGGTGAACAGCGCAGGGCAGCGAGAGGAGTACTTGCTGTGTTTCCACG
	AATTTGGAGTGTTCGTGGATTCTTACGGAAGACGTAGCCGCACAGACGATCTCAAGTGGAGTCGCTT
	ACCTTTGGCCTTTGCCTACAGAGAACCCTATCTGTTTGTGACCCACTTCAACTCACTCGAAGTAATT
	GAGATCCAGGCACGCTCCTCAGCAGGGACCCCTGCCCGAGCGTACCTGGACATCCCGAACCCGCGCT
	ACCTGGGCCCTGCCATTTCCTCAGGAGCGATTTACTTGGCGTCCTCATACCAGGATAAATTAAGGGT
	CATTTGCTGCAAGGGAAACCTCGTGAAGGAGTCCGGCACTGAACACCACCGGGGCCCGTCCACCTCC
	CGCAGCAGCCCCAACAAGCGAGGCCCACCCACGTACAACGAGCACATCACCAAGCGCGTGGCCTCCA
	GCCCAGCGCCGCCCGAAGGCCCCAGCCACCCGCGAGAGCCAAGCACACCCCACCGCTACCGCGAGGG
	GCGGACCGAGCTGCGCAGGGACAAGTCTCCTGGCCGCCCCCTGGAGCGAGAGAAGTCCCCCGGCCGG
	ATGCTCAGCACGCGGAGAGAGCGGTCCCCCGGGAGGCTGTTTGAAGACAGCAGCAGGGGCCGGCTGC
	CTGCGGGAGCCGTGAGGACCCCGCTGTCCCAGGTGAACAAGGTGAGGCAGCATTCCGAGGCCTGTGT
	GTCTGTTGCGGAGGCCAGGAGTGACTTGGGGAACTGA
	ORF Start: ATG at 1		ORF Stop: TGA at 6199
	SEQ ID NO: 14	2066 aa	MW at 236008.5 kD
NOV1g,	MLKFKYGARNPLDAGAAEPIASRASRLNLFFQGKPPFMTQQQMSPLSREGILDALFVLFEECSQPAL
CG106764-02
Protein	MKIKHVSNFVRKCSDTIAELQELQPSAKDFEVRSLVGCGHFAEVQVVREKATGDIYAMKVMKKKALL
Sequence
	AQEQVSFFEEERNILSRSTSPWIPQLQYAFQDKNHLYLVMEYQPGGDLLSLLNRYEDQLDENLIQFY
	LAELILAVHSVHLMGYVHRDIKPENILVDRTGHIKLVDFGSAAKMNSNKVNAKLPIGTPDYMAPEVL
	TVMNGDGKGTYGLDCDWWSVGVIAYEMIYGRSPFAEGTSARTFNNIMNFQRFLKFPDDPKVSSDFLD
	LIQSLLCGQKERLKFEGLCCHPFFSKIDWNNIRNAPPPFVPTLKSDDDTSNFDEPEKNSWVSSSPCQ
	LSPSGFSGEELPFVGFSYSKALGILGRSESVVSGLDSPAKTSSMEKKLLIKSKELODSODKCHKMEO
	EMTRLHRRVSEVEAVLSQKEVELKASETQRSLLEQDLATYITECSSLKRSLEQARMEVSQEDDKALQ
	LLHDIREQSRKLQEIKEQEYQAQVEEMRLMMNQLEEDLVSARRRSDLYESELRESRLAAEEFKRKAT
	ECQHKLLKAKDQGKPEVGEYAKLEKINAEQQLKIQELQEKLEKAVKASTEATELLQNIRQAKERAER
	ELEKLQNREDSSEGIRKKLVEAEERRHSLENKVKRLETMERRENRLKDDIQTKSQQIQQMADKILEL
	EEKHREAQVSAQHLEVHLKQKEQHYEEKIKVLDNQIKKDLADKETLENMMQRHEEEAHEKGKILSEQ
	KAMINAMDSKIRSLEQRIVELSEANKLAANSSLFTQRNMKAQEEMISELRQQKFYLETQAGKLEAQN
	RKLEEQLEKISHQDHSDKNRLLELETRLREVSLEHEEQKLELKRQLTELQLSLQERESQLTALQAAR
	AALESQLRQAKTELEETTAEAEEEIQALTAHRDEIQRKFDALRNSCTVITDLEEQLNQLTEDNAELN
	NQNFYLSKQLDEASGANDEIVQLRSEVDHLRREITEREMQLTSQKQTMEALKTTCTMLEEQVMDLEA
	LNDELLEKERQWEAWRSVLGDEKSQFECRVRELQRMLDTEKQSRARADQRITESRQVVELAVKEHKA
	EILALQQALKEQKLKAESLSDKLNDLEKKHAMLEMNARSLQQKLETERELKQRLLEEQAKLQQQMDL
	QKNHIFRLTQGLQEALDRADLLKTERSDLEYQLENIQVLYSHEKVKMEGTISQQTKLIDFLQAKMDQ
	PAKKKKVPLQYNELKLALEKEKARCAELEEALQKTRIELRSAREEAAHRKATDHPHPSTPATARQQI
	AMSAIVRSPEHQPSAMSLLAPPSSRRKESSTPEEFSRRLKERMHHNIPHRFNVGLNMRATKCAVCLD
	TVHFGRQASKCLECQVMCHPKCSTCLPATCGLPAEYATHFTEAFCRDKMNSPGLQTKEPSSSLHLEG
	WMKVPRNNKRGQQGWDRKYIVLEGSKVLIYDNEAREAGQRPVEEFELCLPDGDVSIHGAVGASELAN
	TAKADVPYILKMESHPHTTCWPGRTLYLLAPSFPDKQRWVTALESVVAGGRVSREKAEADAKLLGNS
	LLKLEGDDRLDMNCTLPFSDQVVLVGTEEGLYALNVLKNSLTHVPGIGAVFQIYIIKDLEKLLMIAG
	EERALCLVDVKKVKQSLAQSHLPAQPDISPNIFEAVKGCHLFGAGKIENGLCICAAMPSKVVILRYN
	ENLSKYCIRKEIETSEPCSCIHFTNYSILIGTNKFYEIDMKQYTLEEFLDKNDHSLAPAVFAASSNS
	FPVSIVQVNSAGQREEYLLCFHEFGVFVDSYGRRSRTDDLKWSRLPLAFAYREPYLFVTHFNSLEVI
	EIQARSSAGTPARAYLDIPNPRYLGPAISSGAIYLASSYQDKLRVICCKGNLVKESGTEHHRGPSTS
	RSSPNKRGPPTYNEHITKRVASSPAPPEGPSHPREPSTPHRYREGRTELRRDKSPGRPLEREKSPGR
	MLSTRRERSPGRLFEDSSRGRLPAGAVRTPLSQVNKVRQHSEACVSVAEARSDLGN

[0350] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 1B.

TABLE 1B
Comparison of NOV1a against NOV1b through NOV1g.
		NOV1a Residues/	Identities/Similarities
	Protein Sequence	Match Residues	for the Matched Region
	NOV1b	1 . . . 615	601/616 (97%)
		5 . . . 620	602/616 (97%)
	NOV1c	615 . . . 1442	690/828 (83%)
		4 . . . 831	691/828 (83%)
	NOV1d	615 . . . 1442	690/843 (81%)
		4 . . . 846	691/843 (81%)
	NOV1e	1436 . . . 2053	618/618 (100%)
		3 . . . 620	618/618 (100%)
	NOV1f	1436 . . . 2053	618/633 (97%)
		3 . . . 635	618/633 (97%)
	NOV1g	1 . . . 2051	1900/2051 (92%)
		1 . . . 2051	1900/2051 (92%)

[0351] Further analysis of the NOV1a protein yielded the following properties shown in Table 1C.

TABLE 1C
Protein Sequence Properties NOV1a
PSort analysis:   0.9800 probability located in nucleus;
                  0.3000 probability located in microbody (peroxisome);
                  0.1000 probability located in mitochondrial matrix
                  space; 0.1000 probability located in lysosome (lumen)
SignalP analysis: No Known Signal Sequence Predicted

[0352] A search of the NOVIa 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 NOV1a
		NOV1a
		Residues/	Identities/
Geneseq	Protein/Organism/Length	Match	Similarities for the	Expect
Identifier	[Patent #, Date]	Residues	Matched Region	Value
AAU03501	Human protein kinase #1 -	1 . . . 2051	2044/2053 (99%)	0.0
	Homo sapiens, 2053 aa.	1 . . . 2053	2046/2053 (99%)
	[WO200138503-A2,
	31-MAY-2001
AAB43359	Human ORFX ORF3123	768 . . . 2053	1286/1286 (100%)	0.0
	polypeptide sequence SEQ	1 . . . 1286	1286/1286 (100%)
	ID NO: 6246 - Homo
	sapiens, 1286 aa.
	[WO200058473-A2,
	05-OCT-2000]
ABB11117	Human RHO/RAC effector	968 . . . 1947	976/980 (99%)	0.0
	homologue, SEQ ID	1 . . . 980	976/980 (99%)
	NO: 1487 - Homo sapiens,
	999 aa.
	[WO200157188-A2,
	09-AUG-2001]
AAU31443	Novel human secreted	1114 . . . 1982	867/869 (99%)	0.0
	protein #1934 - Homo	1 . . . 869	867/869 (99%)
	sapiens, 910 aa.
	[WO200179449-A2,
	25-OCT-2001]
AAE16261	Human kinase PKIN-7	1 . . . 467	463/468 (98%)	0.0
	protein - Homo sapiens,	1 . . . 468	465/468 (98%)
	497 aa.
	[WO200196547-A2,
	20-DEC-2001]

[0353] 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 1E.

TABLE 1E
Public BLASTP Results for NOV1a
		NOV1a
Protein		Residues/	Identities/
Accession		Match	Similarities for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
O88938	Rho/rac-interacting citron	1 . . . 2053	1974/2055 (96%)	0.0
	kinase - Mus musculus	1 . . . 2055	2014/2055 (97%)
	(Mouse), 2055 aa.
O88528	Citron-K kinase - Mus	373 . . . 2053	1599/1683 (95%)	0.0
	musculus (Mouse), 1641 aa	1 . . . 1641	1616/1683 (96%)
	(fragment).
P49025	Citron protein	467 . . . 2053	1563/1589 (98%)	0.0
	(Rho-interacting,	9 . . . 1597	1578/1589 (98%)
	serine/threonine kinase 21) -
	Mus musculus (Mouse),
	1597 aa.
Q9QX19	Postsynaptic density protein -	467 . . . 2053	1556/1619 (96%)	0.0
	Rattus norvegicus (Rat),	1 . . . 1618	1573/1619 (97%)
	1618 aa.
O14578	Citron protein	768 . . . 2053	1286/1286 (100%)	0.0
	(Rho-interacting,	1 . . . 1286	1286/1286 (100%)
	serine/threonine kinase 21) -
	Homo sapiens (Human),
	1286 aa (fragment).

[0354] PFam analysis predicts that the NOV1a protein contains the domains shown in the Table 1F.

TABLE 1F
Domain Analysis of NOV1a
		Identities/
	NOV1a	Similarities for
Pfam Domain	Match Region	the Matched Region	Expect Value
pkinase	97 . . . 359	89/302 (29%)	2.7e−62
		196/302 (65%)
pkinase_C	360 . . . 389	15/32 (47%)	0.00023
		24/32 (75%)
DAG_PE-bind	1389 . . . 1437	14/51 (27%)	6.1e−05
		34/51 (67%)
PH	1470 . . . 1589	20/121 (17%)	1.8e−11
		87/121 (72%)
CNH	1618 . . . 1915	107/378 (28%)	1.5e−110
		289/378 (76%)

Example 2

[0355] 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: 15	1238 bp
NOV2a,	ATGGATGGATGGAGAAGGATGCCTCGCTGGGGACTGCTGCTGCTGCTCTGGGGCTCCTGTACCTTTGG
CG117662-01
DNA Sequence	TCTCCCGACAGACACCACCACCTTTAAACGGATCTTCCTCAAGAGAATGCCCTCAATCCGAGAAAGCC
	TGAAGGAACGAGGTGTGGACATGGCCAGGCTTGGTCCCGAGTGGAGCCAACCCATGAAGAGGCTGACA
	CTTGGCAACACCACCTCCTCCGTGATCCTCACCAACTACATGGACACCCAGTACTATGGCGAGATTGG
	CATCGGCACCCCACCCCAGACCTTCAAAGTCGTCTTTGACACTGGTTCGTCCAATGTTTGGGTGCCCT
	CCTCCAAGTGCAGCCGTCTCTACACTGCCTGTGTGTATCACAAGCTCTTCGATGCTTCGGATTCCTCC
	AGCTACAAGCACAATGGAACAGAACTCACCCTCCGCTATTCAACAGGGACAGTCAGTGGCTTTCTCAG
	CCAGGACATCATCACCGTGGGTGGAATCACGGTGACACAGATGTTTGGAGAGGTCACGGAGATGCCCG
	CCTTACCCTTCATGCTGGCCGAGTTTGATGGGGTTGTGGGCATGGGCTTCATTGAACAGGCCATTGGC
	AGGGTCACCCCTATCTTCGACAACATCATCTCCCAAGGGGTGCTAAAAGAGGACGTCTTCTCTTTCTA
	CTACAACAGAGATTCCGAGAATTCCCAATCGCTGGGAGGACAGATTGTGCTGGGAGGCAGCGACCCCC
	AGCATTACGAAGGGAATTTCCACTATATCAACCTCATCAAGACTGGTGTCTGGCAGATTCAAATGAAG
	GGGGTGTCTGTGGGGTCATCCACCTTGCTCTGTGAAGACGGCTGCCTGGCATTGGTAGACACCGGTGC
	ATCCTACATCTCAGGTTCTACCAGCTCCATAGAGAAGCTCATGGAGGCCTTGGGAGCCAAGAAGAGGC
	TGTTTGATTATGTCGTGAAGTGTAACGAGGGCCCTACACTCCCCGACATCTCTTTCCACCTGGGAGGC
	AAAGAATACACGCTCACCAGCGCGGACTATGTATTTCAGGAATCCTACAGTAGTAAAAAGCTGTGCAC
	ACTGGCCATCCACGCCATGGATATCCCGCCACCCACTGGACCCACCTGGGCCCTGGGGGCCACCTTCA
	TCCGAAAGTTCTACACAGAGTTTGATCGGCGTAACAACCGCATTGGCTTCGCCTCGGCCCGCTGAGGC
	CCTCTGCCACCCAG
	ORF Start: ATG at 1		ORF Stop: TGA at 1219
	SEQ ID NO: 16	406 aa	MW at 45030.9 kD
NOV2a,	MDGWRRMPRWGLLLLLWGSCTFGLPTDTTTFKRIFLKRMPSIRESLKERGVDMARLGPEWSQPMKRLT
CG117662-01
Protein	LGNTTSSVILTNYMDTQYYGEIGIGTPPQTFKVVFDTGSSNVWVPSSKCSRLYTACVYHKLFDASDSS
Sequence
	SYKHNGTELTLRYSTGTVSGFLSQDIITVGGITVTQMFGEVTEMPALPFMLAEFDGVVGMGFIEQAIG
	RVTPIFDNIISQGVLKEDVFSFYYNRDSENSQSLGGQIVLGGSDPQHYEGNFHYINLIKTGVWQIQMK
	GVSVGSSTLLCEDGCLALVDTGASYISGSTSSIEKLMEALGAKKRLFDYVVKCNEGPTLPDISFHLGG
	KEYTLTSADYVFQESYSSKKLCTLAIHAMDIPPPTGPTWALGATFIRKFYTEFDRRNNRIGFASAR
	SEQ ID NO: 17	911 bp
NOV2b,	ATGGATGGATGGAGAAGGATGCCTCGCTGGGGACTGCTGCTGCTGCTCTGGGGCTCCTGTACCTTTG
CG117662-02
DNA Sequence	GTCTCCCGACAGACACCACCACCTTTAAACGGATCTTCCTCAAGAGAATGCCCTCAATCCGAGAAAG
	CCTGAAGGAACGAGGTGTGGACATGGCCAGGCTTGGTCCCGAGTGGAGCCAACCCATGAAGAGGCTG
	ACACTTGGCAACACCACCTCCTCCGTGATCCTCACCAACTACATGGACACCCAGTACTATGGCGAGA
	TTGGCATCGGCACCCCACCCCAGACCTTCAAAGTCGTCTTTGACACTGGTTCGTCCAATGTTTGGGT
	GCCCTCCTCCAAGTGCAGCCGTCTCTACACTGCCTGTGTGTATCACAAGCTCTTCGATGCTTCGGAT
	TCCTCCAGCTACAAGCACAATGGAACAGAACTCACCCTCCGCTATTCAACAGGGACAGTCAGTGGCT
	TTCTCAGCCAGGACATCATCACCGTGTCTGTGGGGTCATCCACCTTACTCTGTGAAGACGGCTGCCT
	GGCATTGGTAGACACCGGTGCATCCTACATCTCAGGTTCTACCAGCTCCATAGAGAAGCTCATGGAG
	GCCTTGGGAGCCAAGAAGAGGCTGTTTGATTATGTCGTGAAGTGTAACGAGGGCCCTACACTCCCCG
	ACATCTCTTTCCACCTGGGAGGCAAAGAATACACGCTCACCAGCGCGGACTATGTATTTCAGGAATC
	CTACAGTAGTAAAAAGCTGTGCACACTGGCCATCCACGCCATGGATATCCCGCCACCCACTGGACCC
	ACCTGGGCCCTGGGGGCCACCTTCATCCGAAAGTTCTACACAGAGTTTGATCGGCGTAACAACCGCA
	TTGGCTTCGCCTCGGCCCGCTGAGGCCCTCTGCCACCCAG
	ORF Start: ATG at 1		ORF Stop: TGA at 892
	SEQ ID NO: 18	297 aa	MW at 33025.3 kD
NOV2b,	MDGWRRMPRWGLLLLLWGSCTFGLPTDTTTFKRIFLKRMPSIRESLKERGVDMARLGPEWSQPMKRL
CG117662-02
Protein	TLGNTTSSVILTNYMDTGYYGEIGIGTPPQTFKVVFDTGSSNVWVPSSKCSRLYTACVYHKLFDASD
Sequence
	SSSYKHNGTELTLRYSTGTVSGFLSQDIITVSVGSSTLLCEDGCLALVDTGASYISGSTSSIEKLME
	ALGAKKRLFDYVVKCNEGPTLPDISFHLGGKEYTLTSADYVFQESYSSKKLCTLAIHAMDIPPPTGP
	TWALGATFIRKFYTEFDRRNNRIGFASAR

[0356] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 2B.

TABLE 2B
Comparison of NOV2a against NOV2b.
Protein Sequence	NOV2a Residues/	Identities/Similarities
	Match Residues	for the Matched Region
NOV2b	1 . . . 165	165/165 (100%)
	1 . . . 165	165/165 (100%)

[0357] Further analysis of the NOV2a protein yielded the following properties shown in Table 2C.

TABLE 2C
Protein Sequence Properties NOV2a
PSort analysis:   0.3700 probability located in outside;
                  0.2541 probability located in microbody (peroxisome);
                  0.1900 probability located in lysosome (lumen);
                  0.1000 probability located in endoplasmic
                  reticulum (membrane)
SignalP analysis: Cleavage site between residues 24 and 25

[0358] A search of the NOV2a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 2D.

TABLE 2D
Geneseq Results for NOV2a
		NOV2a	Identities/
		Residues/	Similarities
Geneseq	Protien/Organism/Length	Match	for the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	value
AAW23244	Human renin - Homo sapiens,	1 . . . 406	404/406 (99%)	0.0
	406 aa. [WO9728684-A1,	1 . . . 406	404/406 (99%)
	14-AUG-1997]
AAP50135	Sequence of pre-pro-renin -	1 . . . 406	404/406 (99%)	0.0
	Homo sapiens, 406 aa.	1 . . . 406	404/406 (99%)
	[EP135347-A,
	27-MAR-1985]
ABB11781	Human renin homologue,	1 . . . 406	391/408 (95%)	0.0
	SEQ ID NO: 2151 - Homo	31 . . . 438	393/408 (95%)
	sapiens, 438 aa.
	[WO200157188-A2,
	09-AUG-2001]
AAU72879	Human aspartyl protease	24 . . . 405	169/400 (42%)	1e−90
	partial protein sequence #4 -	14 . . . 409	246/400 (61%)
	Homo sapiens, 412 aa.
	[WO200183782-A2,
	08-NOV-2001]
AAY93685	Amino acid sequence of	24 . . . 405	169/400 (42%)	1e−90
	novel polypeptide PRO292 -	14 . . . 409	246/400 (61%)
	Homo sapiens, 412 aa.
	[WO200037640-A2,
	29-JUN-2000]

[0359] 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 for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
P00797	Renin precursor, renal (EC	1 . . . 406	405/406 (99%)	0.0
	3.4.23.15)	1 . . . 406	405/406 (99%)
	(Angiotensinogenase) - Homo
	sapiens (Human), 406 aa.
Q9TSZ1	Preprorenin precursor (EC	1 . . . 406	381/406 (93%)	0.0
	3.4.23.15) - Callithrix jacchus	1 . . . 400	389/406 (94%)
	(Common marmoset), 400 aa.
P52115	renin precursor, renal (EC	7 . . . 406	292/401 (72%)	e−175
	3.4.23.15)	1 . . . 400	338/401 (83%)
	(Angiotensinogenase) - Ovis
	aries (Sheep), 400 aa.
Q15296	Kidney mRNA fragment for	108 . . . 406	297/300 (99%)	e−172
	renin (Aa 105-401) - Homo	1 . . . 300	298/300 (99%)
	sapiens (Human), 300 aa
	(fragment).
P06281	Renin precursor, renal (BC	5 . . . 406	281/403 (69%)	e−167
	3.4.23.15)	4 . . . 402	331/403 (81%)
	(Angiotensinogenase) - Mus
	musculus (Mouse), 402 aa.

[0360] PFam analysis predicts that the NOV2a protein contains the domains shown in the Table 2F.

TABLE 2F
Domain Analysis of NOV2a
		Identities/
	NOV2a	Similarities for
Pfam Domain	Match Region	the Matched Region	Expect Value
asp	31 . . . 405	174/428(41%)	4.le−197
		339/428 (79%)

Example 3

[0361] The NOV3 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 3A.

TABLE 3A
NOV3 Sequence Analysis
	SEQ ID NO:19	2827 bp
NOV3a,	TGGCGATGCTACTGTTTAATTGCAGGAGGTGGGGGTGTGTGTACCATGTACCAGGGCTATTAGAAGCA
CG118051-01
DNA Sequence	AGAAGGAAGGAGGGAGGGCAGAGCGCCCTGCTGAGCAACAAAGGACTCCTGCAGCCTTCTCTGTCTGT
	CTCTTGGCACAGGCACATGGGGAGGCCTCCCGCAGGTGGGGGGCCACCAGTCCAGGGGTGGGAGCACT
	ACAGGGCACGAGTTGGTTTGGGAGCTGCCAGTCTCCTGGGAGGATCGCAGTCAGCAGAGCAGGGCTGA
	GGCCTGGGGGTAGGAGCAGAGCCTGCGCATCTGGAGGCAGCATGTCCAAGAAAGGGAGTGGAGGTGCA
	GCGAAGGACCCAGGGGCAGAGCCCACGCTGGGGATGGACCCCTTCGAGGACACACTGCGGCGGCTGCG
	TGAGGCCTTCAACTGAGGGCGCACGCGGCCGGCCGAGTTCCGGGCTGCGCAGCTCCAGGGCCTGGGCC
	ACTTCCTTCAAGAAAACAAGCAGCTTCTGCGCGACGTGCTGGCCCAGGACCTGCATAAGCCAGCTTTC
	GAGGCAGACATATCTGAGCTCATCCTTTGCCAGAACGAGGTTGACTACGCTCTCAAGAACCTTCAGGC
	CTGGATGAAGGATGAACCACGGTCCACGAACCTGTTCATGAAGCTGGACTCGGTCTTCATCTGGAAGG
	AACCCTTTGGCCTGGTCCTCATCATCGCACCCTGGAACTACCCATTGAACCTGACCCTGGTGCTCCTG
	GTGGGCACCCTCCCCGCAGGGAATTGCGTGGTGCTGAAGCCGTCAGAAATCAGCCAGGGCACAGAGAA
	GGTCCTGGCTGAGGTGCTGCCCCAGTACCTGGACCAGAGCTGCTTTGCCGTGGTGCTGGGCGGACCCC
	AGGAGACAGGGCAGCTGCTAGAGCACAAGTTGGACTACATCTTCTTCACAGGGAGCCCTCGTGTGGGC
	AAGATTGTCATGACTGCTGCCACCAAGCACCTGACGCCTGTCACCCTGGAGCTGGGGGGCAAGAACCC
	CTGCTACGTGGACGACAACTGCGACCCCCAGACCGTGGCCAACCGCGTGGCCTGGTTCTGCTACTTCA
	ATGCCGGCCAGACCTGCGTGGCCCCTGACTACGTCCTGTGCAGCCCCGAGATGCAGGAGAGGCTGCTG
	CCCGCCCTGCAGAGCACCATCACCCGTTTCTATGGCGACGACCCCCAGAGCTCCCCAAACCTGGGCCG
	CATCATCAACCAGAAACAGTTCCAGCGGCTGCGGGCATTGCTGGGCTGCGGCCGCGTGGCCATTGGGG
	GCCAGAGCAACGAGAGCGATCGCTACATCGCCCCCACGGTGCTGGTGGACGTGCAGGAGACGGAGCCT
	GTGATGCAGGAGGAGATCTTCGGGCCCATCCTGCCCATCGTGAACGTGCAGAGCGTGGACGAGGCCAT
	CAAGTTCATCAACCGGCAGGAGAAGCCCCTGGCCCTGTACGCCTTCTCCAACAGCAGACAGGTTGTGA
	ACCAGATGCTGGAGCGGACCAGCAGCGGCAGCTTTGGAGGCAATGAGGGCTTCACCTACATATCTCTG
	CTGTCCGTGCCATTCGGGGGAGTCGGCCACAGTGGGATGGGCCGGTACCACGGCAAGTTCACCTTCGA
	CACCTTCTCCCACCACCGCACCTGCCTGCTCGCCCCCTCCGGCCTGGAGAAATTAAAGGAGATCCGCT
	ACCCACCCTATACCGACTGGAACCAGCAGCTGTTACGCTGGGGCATGGGCTCCCAGAGCTGCACCCTC
	CTGTGAGCGTCCCACCCGCCTCCAACGGGTCACACAGAGAAACCTGAGTCTAGCCATGAGGGGCTTAT
	GCTCCCAACTCACATTGTTCCTCCAGACCGCAGGCTCCCCCAGCCTCAGGTTGCTGGAGCTGTCACAT
	GACTGCATCCTGCCTGCCAGGGCTGCAAAGCAAGGTCTTGCTTCTATCTGGGGGACGCTGCTCGAGAG
	AGGCCGAGAGGCCGCAGAACATGCCAGGTGTCCTCACTCACCCCACCCTCCCCAATTCCAGCCCTTTG
	CCCTCTCGGTCAGGGTTGGCCAGGCCCAGTCACAGGGGCAGTGTCACCCTGGAAAATACAGTGCCCTG
	CCTTCTTAGGGGCATCAGCCCTGAACGGTTGAGAGCGTGGAGCCCTCCAGGCCTTTGCTCTCCCCTCT
	AGGCACACGCGCACTTCCACCTCTGCCCCATCCCAACTGCACCAGCACTGCCTCCCCCAGGGATCCTC
	TCACATCCCACACTGGTCTCTGCACCACCCCTCTGGTTCACACCGCACCCTGCACTCACCCACAGCAG
	CTCCATCCACTGGGAAAACTGGGGTTTGCATCACTCCACTGCACAGTGTTAGTGGGACCTGGGGGCAA
	GTCCCTTGACTTCTCTGAGCCTCAGTTTCCTTATGTGAAAGTTGCTGGAACCAAAATGGAGTCACTTA
	TGCCAAACTCTAATAAAATGGAGTCGGGGGGGCACATAGAAGCCCTCACACACACATGCCCGTAACAG
	GATTTATCACCAAGACACGCCTGCATGTAAGACCAGACACAGGGCGTATGGAAAAGCACGTCCTCAAA
	GACTGTAGTATTCCAGATGAGCTGCAGATGCTTACCTACCACGGCCGTCTCCACCAGAAAACCATCGC
	CAACTCCTGCGATCAGCTTGTGACTTACAAACCTTGTTTAAAAGCTGCTTACATGGACTTCTGTCCTT
	TAAAACGTTCCCCTTGGCTGTGGCCCTCTGTGTATGCCTGGGATCCTTCCAAGCACTCATAGCCCAGA
	TAGGAATCCTCTGCTCCTCCCAAATAAATTCATCTGTTC
	ORF Start: ATG at 617		ORF Stop: TGA at 1772
	SEQ ID NO: 20	385 aa	MW at 42794.8 kD
NOV3a,	MKDEPRSTNLFMKLDSVFIWKEPFGLVLIIAPWNYPLNTLTVLLVGTLPAGNCVVLKPSEISQGTEKV
CG118051-01
Protein	LAEVLPQYLDQSCFAVVLGGPQETGQLLEHKLDYIFFTGSPRVGKIVMTAATKHLTPVTLELGGKNPC
Sequence
	YVDDNCDPQTVANRVAWFCYFNAGQTCVAPDYVLCSPEMQERLLPALQSTITRFYGDDPQSSPNLGRI
	INQKQFQRLRALLGCGRVAIGGQSNESDRYIAPTVLVDVQETEPVMQEEIFGPILPIVNVQSVDEAIK
	FINRQEKPLALYAFSNSRQVVNQMLERTSSGSFGGNEGFTYISLLSVPFGGVGHSGMGRYHGKFTFDT
	FSHHRTCLLAPSGLEKLKEIRYPPYTDWNQQLLRWGMGSQSCTLL
	SEQ ID NO:21	1586 bp
NOV3b,	CACGAGTTGGTTTGGGAGCTGCCAGTCTCCTGGGAGGATCGCAGTCAGCAGAGCAGGGCTGAGGCCT
CG118051-02
DNA Sequence	GGGGGTAGGAGCAGAGCCTGCGCATCTGGAGGCAGCATGTCCAAGAAAGGGAGTGGAGGTGCAGCGA
	AGGACCCAGGGGCAGAGCCCACGCTGGGGATGGACCCCTTCGAGGACACACTGCGGCGGCTGCGTGA
	GGCCTTCAACTGAGGGCGCACGCGGCCGGCCGAGTTCCGGGCTGCGCAGCTCCAGGGCCTGGGCCAC
	TTCCTTCAAGAAAACAAGCAGCTTCTGCGCGACGTGCTGGCCCAGGACCTGCATAAGCCAGCTTTCG
	AGGCAGACATATCTGAGCTCATCCTTTGCCAGAACGAGGTTGACTACGCTCTCAAGAACCTTCAGGC
	CTGGATGAAGGATGAACCACGGTCCACGAACCTGTTCATGAAGCTGGACTCGGTCTTCATCTGGAAG
	GAACCCTTTGGCCTGGTCCTCATCATCGCACCCTGGAACTACCCATTGAACCTGACCCTGGTGCTCC
	TGGTGGGCACCCTCCCCGCAGGGAATTGCGTGGTGCTGAAGCCGTCAGAAATCAGCCAGGGCACAGA
	GAAGGTCCTGGCTGAGGTGCTGCCCCAGTACCTGGACCAGAGCTGCTTTGCCGTGGTGCTGGGCGGA
	CCCCAGGAGACAGGGCAGCTGCTAGAGCACAAGTTGGACTACATCTTCTTCACAGGGAGCCCTCGTG
	TGGGCAAGATTGTCATGACTGCTGCCACCAAGCACCTGACGCCTGTCACCCTGGAGCTGGGGGGCAA
	GAACCCCTGCTACGTGGACGACAACTGCGACCCCCAGACCGTGGCCAACCGCGTGGCCTGGTTCTGC
	TACTTCAATGCCGGCCAGACCTGCGTGGCCCCTGACTACGTCCTGTGCAGCCCCGAGATGCAGGAGA
	GGCTGCTGCCCGCCCTGCAGAGCACCATCACCCGTTTCTATGGCGACGACCCCCAGAGCTCCCCAAA
	CCTGGGCCGCATCATCAACCAGAAACAGTTCCAGCGGCTGCGGGCATTGCTGGGCTGCGGCCGCGTG
	GCCATTGGGGGCCAGAGCAACGAGAGCGATCGCTACATCGCCCCCACGGTGCTGGTGGACGTGCAGG
	AGACGGAGCCTGTGATGCAGGAGGAGATCTTCGGGCCCATCCTGCCCATCGTGAACGTGCAGAGCGT
	GGACGAGGCCATCAAGTTCATCAACCGGCAGGAGAAGCCCCTGGCCCTGCACAGTGGGATGGGCCGG
	TACCACGGCAAGTTCACCTTCGACACCTTCTCCCACCACCGCACCTGCCTGCTCGCCCCCTCCGGCC
	TGGAGAAATTAAAGGAGATCCGCTACCCACCCTATACCGACTGGAACCAGCAGCTGTTACGCTGGGG
	CATGGGCTCCCAGAGCTGCACCCTCCTGTGAGCGTCCCACCCGCCTCCAACGGGTCACACAGAGAAA
	CCTGAGTCTAGCCATGAGGGGCTTATGCTCCCAACTCACATTGTTCCTCCAGACCGCAGGCTCCCCC
	AGCCTCAGGTTGCTGGAGCTGTCACATGACTGCATCCTGCCTGCC
	ORF Start: ATG at 407		ORF Stop: TGA at 1436
	SEQ ID NO: 22	343 aa	MW at 38350.9 kD
NOV3b,	MKDEPRSTNLFMKLDSVFIWKEPFGLVLIIAPWNYPLNLTLVLLVGTLPAGNCVVLKPSEISQGTEK
CG118051-02
Protein	VLAEVLPQYLDQSCFAVVLGGPQETGQLLEHKLDYIFFTGSPRVGKIVMTAATKHLTPVTLELGGKN
Sequence
	PCYVDDNCDPQTVANRVAWFCYFNAGQTCVAPDYVLCSPEMQERLLPALQSTITRFYGDDPQSSPNL
	GRIINQKQFQRLRALLGCGRVAIGGQSNESDRYIAPTVLVDVQETEPVMQEEIFGPILPIVNVQSVD
	EAIKFINRQEKPLALHSGMGRYHGKFTFDTFSHHRTCLLAPSGLEKLKEIRYPPYTDWNQQLLRWGM
	GSQSCTLL
	SEQ ID NO:23	1791 bp
NOV3c	TTAAGGAGAATCTTAAAGTGAGGGCTGAGGGACTCTCCTGATCCAGAGCTGAGGACTCTCCTGATCCA
CG118051-03
DNA Sequence	GAGCTGAGGGCTCTCCTGATGGACCCCTTCGAGGACACGCTGCGGCGGCTGCGTGAGGCCTTCAACTG
	AGGGCGCACGCGGCCGGCCGAGTTCCGGGCTGCGCAGCTCCAGGGCCTGGGCCACTTCCTTCAAGAAA
	ACAAGCAGCTTCTGCGCGACGTGCTGGCCCAGGACCTGCATAAGCCAGCTTTCGAGGCAGACATATCT
	GAGCTCATCCTTTGCCAGAACGAGGTTGACTACGCTCTCAAGAACCTTCAGGCCTGGATGAAGGATGA
	ACCACGGTCCACGAACCTGTTCATGAAGCTGGACTCGGTCTTCATCTGGAAGGAACCCTTTGGCCTGG
	TCCTCATCATCGCACCCTGGAACTACCCACTGAACCTGACCCTGGTGCTCCTGGTGGGCGCCCTCGCC
	GCAGGGAATTGCGTGGTGCTGAAGCCGTCAGAAATCAGCCAGGGCACAGAGAAGGTCCTGGCTGAGGT
	GCTGCCCCAGTACCTGGACCAGAGCTGCTTTGCCGTGGTGCTGGGCGGACCCCAGGAGACAGGGCAGC
	TGCTAGAGCACAAGTTGGACTACATCTTCTTCACAGGGAGCCCTCGTGTGGGCAAGATTGTCATGACT
	GCTGCCACCAAGCACCTGACGCCTGTCACCCTGGAGCTGGGGGGCAAGAACCCCTGCTACGTGGACGA
	CAACTGCGACCCCCAGACCGTGGCCAACCGCGTGGCCTGGTTCTGCTACTTCAATGCCGGCCAGACCT
	GCGTGGCCCCTGACTACGTCCTGTGCAGCCCCGAGATGCAGGAGAGGCTGCTGCCCGCCCTGCAGAGC
	ACCATCACCCGTTTCTATGGCGACGACCCCCAGAGCTCCCCAAACCTGGGCCGCATCATCAACCAGAA
	ACAGTTCCAGCGGCTGCGGGCATTGCTGGGCTGCGGCCGCGTGGCCATTGGGGGCCAGAGCAACGAGA
	GCGATCGCTACATCGCCCCCACGGTGCTGGTGGACGTGCAGGAGACGGAGCCTGTGATGCAGGAGGAG
	ATCTTCGGGCCCATCCTGCCCATCGTGAACGTGCAGAGCGTGGACGAGGCCATCAAGTTCATCAACCG
	GCAGGAGAAGCCCCTGGCCCTGTACGCCTTCTCCAACAGCAGCCAGGTTGTGAACCAGATGCTGGAGC
	GGACCAGCAGCGGCAGCTTTGGAGGCAATGAGGGCTTCACCTACATATCTCTGCTGTCCGTGCCATTC
	GGGGGAGTCGGCCACAGTGGGATGGGCCGGTACCACGGCAAGTTCACCTTCGACACCTTCTCCCACCA
	CCGCACCTGCCCGCTCGCCCCCTCCGGCCTGGAGAAATTAAAGGAGATCCGCTACCCACCCTATACCG
	ACTGGAACCAGCAGCTGTTACGCTGGGGCATGGGCTCCCAGAGCTGCACCCTCCTGTGAGCGTCCCAC
	CCGCCTCCAACGGGTCACACAGAGAAACCTGAGTCTAGCCATGAGGGGCTTATGCTCCCAACTCACAT
	TGTTCCTCCAGACCGCAGGCTCCCCCAGCCTCAGGTTGCTGGAGCTGTCACATGACTGCATCCTGCCT
	GCCAGGGCTGCAAAGCAAGGTCTTGCTTCTATCTGGGGGACGCTGCTCGAGAGAGGCCGAGAGGCCGC
	AGAACATGCCAGGTGTCCTCACTCACCCCACCCTCCCCAATTCCAGCCCTTTGCCCTCTCGGTCAGGG
	TTGACCAGGCCAAGGGCTAGCAT
	ORF Start: ATG at 330		ORF Stop: TGA at 1485
	SEQ ID NO:24	385 aa	MW at 42653.5kD
NOV3c,	MKDEPRSTNLFMKLDSVFIWKEPFGLVLIIAPWNYPLNLTLVLLVGALAAGNCVVLKPSEISQGTEKV
CG118051-03
Protein	LAEVLPQYLDQSCFAVVLGGPQETGQLLEHKLDYIFFTGSPRVGKIVMTAATKHLTPVTLELGGKNPC
Sequence
	YVDDNCDPQTVANRVAWFCYFNAGQTCVAPDYVLCSPEMQERLLPALQSTITRFYGDDPQSSPNLGRI
	INQKQFQRLRALLGCGRVAIGGQSNESDRYIAPTVLVDVQETEPVMQEEIFGPILPIVNVQSVDEAIK
	FINRQEKPLALYAFSNSSQVVNQMLERTSSGSFGGNEGFTYISLLSVPFGGVGHSGMGRYHGKFTFDT
	FSHHRTCPLAPSGLEKLKEIRYPPYTDWNQQLLRWGMGSQSCTLL

[0362] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 3B.

TABLE 3B
Comparison of NOV3a against NOV3b and NOV3c.
	NOV3a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV3b	1 . . . 385	331/385 (85%)
	1 . . . 343	331/385 (85%)
NOV3c	1 . . . 385	363/385 (94%)
	1 . . . 385	363/385 (94%)

[0363] Further analysis of the NOV3a protein yielded the following properties shown in Table 3C.

TABLE 3C
Protein Sequence Properties NOV3a
PSort analysis:   0.7900 probability located in plasma membrane;
                  0.3000 probability located in Golgi body;
                  0.2000 probability located in endoplasmic
                  reticulum (membrane);
                  0.1743 probability located in microbody (peroxisome)
SignalP analysis: Cleavage site between residues 54 and 55

[0364] 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
		NOV3a	Identities/
		Residues/	Similarities
Geneseq	Protein/Organism/Length	Match	for the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAB58156	Lung cancer associated	1 . . . 353	325/353 (92%)	0.0
	polypeptide sequence SEQ ID	62 . . . 414	337/353 (95%)
	494 - Homo sapiens, 430 aa.
	[WO200055180-A2,
	21-SEP-2000]
ABB66868	Drosophila melanogaster	14 . . . 309	158/296 (53%)	3e−94
	polypeptide SEQ ID NO	95 . . . 390	212/296 (71%)
	27396 - Drosophila
	melanogaster, 561 aa.
	[WO200171042-A2,
	27-SEP-2001]
ABB65492	Drosophila melanogaster	14 . . . 309	158/296 (53%)	3e−94
	polypeptide SEQ ID NO	95 . . . 390	212/296 (71%)
	23268 - Drosophila
	melanogaster, 561 aa.
	[WO200171042-A2,
	27-SEP-2001]
ABP39856	Staphylococcus epidermidis	2 . . . 365	157/366 (42%)	1e−85
	ORF amino acid sequence	88 . . . 451	235/366 (63%)
	SEQ ID NO: 4701 -
	Staphylococcus epidermidis,
	464 aa. [US6380370-B1,
	30-APR-2002]
AAG82730	S. epidermidis open reading	2 . . . 365	157/366 (42%)	1e−85
	frame protein sequence SEQ	83 . . . 446	235/366 (63%)
	ID NO: 2554 -
	Staphylococcus
	epidermidis, 459 aa.
	[WO200134809-A2,
	17-MAY-2001]

[0365] 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
		NOV3a
Protein		Residues/	Identities/
Accession		Match	Similarities for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
P48448	Aldehyde dehydrogenase 8	1 . . . 385	385/385 (100%)	0.0
	(EC 1.2.1.5) - Homo sapiens	1 . . . 385	385/385 (100%)
	(Human), 385 aa.
BAC03897	CDNA FLJ35145 fis, clone	1 . . . 385	380/385 (98%)	0.0
	PLACE6009853, highly	1 . . . 385	381/385 (98%)
	similar to ALDEHYDE
	DEHYDROGENASE 8 (BC
	1.2.1.5) - Homo sapiens
	(Human), 385 aa.
P43353	Aldehyde dehydrogenase 7	1 . . . 385	321/387 (82%)	0.0
	(EC 1.2.1.5) - Homo sapiens	82 . . . 468	345/387 (88%)
	(Human), 468 aa.
AAH33099	Similar to aldehyde	13. . . 385	315/375 (84%)	0.0
	dehydrogenase 3 family,	57 . . . 431	339/375 (90%)
	member B1 - Homo sapiens
	(Human), 431 aa.
Q8VHW0	Aldehyde dehydrogenase	1 . . . 385	295/387 (76%)	e−174
	ALDH3B1 (EC 1.2.1.3) -	63 . . . 449	336/387 (86%)
	Mus musculus (Mouse), 449
	aa (fragment).

[0366] PFam analysis predicts that the NOV3a protein contains the domains shown in the Table 3F.

TABLE 3F
Domain Analysis of NOV3a
			Identities/
		NOV3a	Similarities
	Pfam	Match	for the Matched	Expect
	Domain	Region	Region	Value
	aldedh	1 . . . 351	129/492 (26%)	1.1e−103
			299/492 (61%)

Example 4.

[0367] The NOV4 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 4A.

TABLE 4A
NOV4 Sequence Analysis
	SEQ ID NO:25	1636 bp
NOV4a,	CCAGGAGCCCCAGTTACCGGGAGAGGCTGTGTCAAAGGCGCCATGAGCAAGATCAGCGAGGCCGTGAA
CG120277-01
DNA Sequence	GCGCGCCCGCGCCGCCTTCAGCTCGGGCAGGACCCGTCCGCTGCAGTTCCGATTCCAGCAGCTGGAGG
	CGCTGCAGCGCCTGATCCAGGAGCAGGAGCAGGAGCTGGTGGGCGCGCTGGCCGCAGACCTGCACAAG
	AATGAATGGAACGCCTACTATGAGGAGGTGGTGTACGTCCTAGAGGAGATCGAGTACATGATCCAGAA
	GCTCCCTGAGTGGGCCGCGGATGAGCCCGTGGAGAAGACGCCCCAGACTCAGCAGGACGAGCTCTACA
	TCCACTCGGAGCCACTGGGCGTGGTCCTCGTCATTGGCACCTGGAACTACCCCTTCAACCTCACCATC
	CAGCCCATGGTGGGCGCCATCGCTGCAGGGAACGCAGTGGTCCTCAAGCCCTCGGAGCTGAGTGAGAA
	CATGGCGAGCCTGCTGGCTACCATCATCCCCCAGTACCTGGACAAGGATCTGTACCCAGTAATCAATG
	GGGGTGTCCCTGAGACCACGGAGCTGCTCAAGGAGAGGTTCGACCATATCCTGTACACGGGCAGCACG
	GGGGTGGGGAAGATCATCATGACGGCTGCTGCCAAGCACCTGACCCCTGTCACGCTGGAGCTGGGAGG
	GAAGAGTCCCTGCTACGTGGACAAGAACTGTGACCTGGACGTGGCCTGCCGACGCATCGCCTGGGGGA
	AATTCATGAACAGTGGCCAGACCTGCGTGGCCCCAGACTACATCCTCTGTGACCCCTCGATCCAGAAC
	CAAATTGTGGAGAAGCTCAAGAAGTCACTGAAAGAGTTCTACGGGGAAGATGCTAAGAAATCCCGGGA
	CTATGGAAGAATCATTAGTGCCCGGCACTTCCAGAGGGTGATGGGCCTGATTGAGGGCCAGAAGGTGG
	CTTATGGGGGCACCGGGGATGCCGCCACTCGCTACATAGCCCCCACCATCCTCACGGACGTGGACCCC
	CAGTCCCCGGTGATGCAAGAGGAGATCTTCGGGCCTGTGCTGCCCATCGTGTGCGTGCGCAGCCTGGA
	GGAGGCCATCCAGTTCATCAACCAGCGTGAGAAGCCCCTGGCCCTCTACATGTTCTCCAGCAACGACA
	AGGTGATTAAGAAGATGATTGCAGAGACATCCAGTGGTGGGGTGGCGGCCAACGATGTCATCGTCCAC
	ATCACCTTGCACTCTCTGCCCTTCGGGGGCGTGGGGAACAGCGGCATGGGATCCTACCATGGCAAGAA
	GAGCTTCGAGACTTTCTCTCACCGCCGCTCTTGCCTGGTGAGGCCTCTGATGAATGATGAAGGCCTGA
	AGGTCAGATACCCCCCGAGCCCGGCCAAGATGACCCAGCACTGAGGAGGGGTTGCTCCGCCTGGCCTG
	GCCATACTGTGTCCCATCGGAGTGCGGACCACCCTCACTGGCTCTCCTGGCCCTGGAGAATCGCTCCT
	GCAGCCCCAGCCCAGCCCCACTCCTCTGCTGACCTGCTGACCTGTGCACACCCCACTCCCACATGGGC
	CCAGGCCTCACCATTCCAAGTCTCCACCCCTTTCTAGACCAATAAAGAGACAAATACAATTTTCTAAC
	TCGG
	ORF Start: ATG at 43		ORF Stop: TGA at 1402
	SEQ ID NO:26	453 aa	MW at 50412.5 kD
NOV4a,	MSKISEAVKRARAAFSSGRTRPLQFRFQQLEALQRLIQEQEQELVGALAADLHKNEWNAYYEEVVYVL
CG120277-01
Protein	EEIEYMIQKLPEWAADEPVEKTPQTQQDELYIHSEPLGVVLVIGTWNYPFNLTIQPMVGAIAAGNAVV
Sequence
	LKPSELSENMASLLATIIPQYLDKDLYPVINGGVPETTELLKERFDHILYTGSTGVGKIIMTAAAKHL
	TPVTLELGGKSPCYVDKNCDLDVACRRIAWGKFMNSGQTCVAPDYILCDPSIQNQIVEKLKKSLKEFY
	GEDAKKSRDYGRIISARHFQRVMGLIEGQKVAYGGTGDAATRYIAPTILTDVDPQSPVMQEEIFGPVL
	PIVCVRSLEEAIQFINQREKPLALYMFSSNDKVIKKMIAETSSGGVAANDVIVHITLHSLPFGGVGNS
	GMGSYHGKKSFETFSHRRSCLVRPLMNDEGLKVRYPPSPAKMTQH
	SEQ ID NO:27	1554 bp
NOV4b,	GAGCCCCAGTTACCGGGAGAGGCTGTGTCAAAGGCGCCATGAGCAAGATCAGCGAGGCCGTGAAGCG
CG120277-02
DNA Sequence	CGCCCGCGCCGCCTTCAGCTCGGGCAGGACCCGTCCGCTGCAGTTCCGGATCCAGCAGCTGGAGGCG
	CTGCAGCGCCTGATCCAGGAGCAGGAGCAGGAGCTGGTGGGCGCGCTGGCCGCAGACCTGCACAAGA
	ATGAATGGAACGCCTACTATGAGGAGGTGGTGTACGTCCTAGAGGAGATCGAGTACATGATCCAGAA
	GCTCCCTGAGTGGGCCGCGGATGAGCCCGTGGAGAAGACGCCCCAGACTCAGCAGGACGAGCTCTAC
	ATCCACTCGGAGCCACTGGGCGTGGTCCTCGTCATTGGCACCTGGAACTACCCCTTCAACCTCACCA
	TCCAGCCCATGGTGGGCGCCATCGCTGCAGGGAACGCAGTGGTCCTCAAGCCCTCGGAGCTGAGTGA
	GAACATGGCGAGCCTGCTGGCTACCATCATCCCCCAGTACCTGGACAAGGATCTGTACCCAGTAATC
	AATGGGGGTGTCCCTGAGACCACGGAGCTGCTCAAGGAGAGGTTCGACCATATCCTGTACACGGGCA
	GCACGGGGGTGGGGAAGATCATCATGACGGCTGCTGCCAAGCACCTGACCCCTGTCACGCTGGAGCT
	GGGAGGGAAGAGTCCCTGCTACGTGGACAAGAACTGTGACCTGGACGTGGCCTGCCGACGCATCGCC
	TGGGGGAAATTCATGAACAGTGGCCAGACCTGCGTGGCCCCAGACTACATCCTCTGTGACCCCTCGA
	TCCAGAACCAAATTGTGGAGAAGCTCAAGAAGTCACTGAAAGAGTTCTACGGGGAAGATGCTAAGAA
	ATCCCGGGACTATGGAAGAATCATTAGTGCCCGGCACTTCCAGAGGGTGATGGGCCTGATTGAGGGC
	CAGAAGGTGGCTTATGGGGGCACCGGGGATGCCGCCACTCGCTACATAGCCCCCACCATCCTCACGG
	ACGTGGACCCCCAGTCCCCGGTGATGCAAGAGGAGATCTTCGGGCCTGTGCTGCCCATCGTGTGCGT
	GCGCAGCCTGGAGGAGGCCATCCAGTTCATCAACCAGCGTGAGAAGCCCCTGGCCCTCTACATGTTC
	TCCAGCAACGACAAGGTGATTAAGAAGATGATTGCAGAGACATCCAGTGGTGGGGTGGCGGCCAACG
	ATGTCATCGTCCACATCACCTTGCACTCTCTGCCCTTCGGGGGCGTGGGGAACAGCGGCATGGTGAG
	GCCTCTGATGAATGATGAAGGCCTGAAGGTCAGATACCCCCCGAGCCCGGCCAAGATGACCCAGCAC
	TGAGGAGGGGTTGCTCCGTCTGGCCTGGCCATACTGTGTCCCATCGGAGTGCGGACCACCCTCACTG
	GCTCTCCTGGCCCTGGGAGAATCGCTCCTGCAGCCCCAGCCCAGCCCCACTCCTCTGCTGACCTGCT
	GACCTGTGCACACCCCACTCCCACATGGGCCCAGGCCTCACCATTCCAAGTCTCCACCCCTTTCTAG
	ACCAATAAAGAGA
	ORF Start: ATG at 39		ORF Stop: TGA at 1341
	SEQ ID NO:28	434 aa	MW at 48169.0 kD
NOV4b,	MSKISEAVKRARAAFSSGRTRPLQFRIQQLEALQRLIQEQEQELVGALAADLHKNEWNAYYEEVVYV
CG120277-02
Protein	LEEIEYMIQKLPEWAADEPVEKTPQTQQDELYIHSEPLGVVLVIGTWNYPFNLTIQPMVGAIAAGNA
Sequence
	VVLKPSELSENMASLLATIIPQYLDKDLYPVINGGVPETTELLKERFDHILYTGSTGVGKIIMTAAA
	KHLTPVTLELGGKSPCYVDKNCDLDVACRRIAWGKFMNSGQTCVAPDYILCDPSIQNQIVEKLKKSL
	KEFYGEDAKKSRDYGRIISARHFQRVMGLIEGQKVAYGGTGDAATRYIAPTILTDVDPQSPVMQEEI
	FGPVLPIVCVRSLEEAIQFINQREKPLALYMFSSNDKVIKKMIAETSSGGVAANDVIVHITLHSLPF
	GGVGNSGMVRPLMNDEGLKVRYPPSPAKMTQH

[0368] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 4B.

TABLE 4B
Comparison of NOV4a against NOV4b.
		Identities/
		Similarities
Protein	NOV4a Residues/	for the Matched
Sequence	Match Residues	Region
NOV4b	1 . . . 453	401/453 (88%)
	1 . . . 434	401/453 (88%)

[0369] Further analysis of the NOV4a protein yielded the following properties shown in Table 4C.

TABLE 4C
Protein Sequence Properties NOV4a
PSort analysis:   0.7636 probability located in mitochondrial matrix
                  space; 0.4422 probability located in mitochondrial
                  inner membrane; 0.4422 probability located in
                  mitochondrial intermembrane space; 0.4422
                  probability located in mitochondrial
                  outer membrane
SignalP analysis: No Known Signal Sequence Predicted

[0370] 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/
		NOV4a	Similarities for
Geneseq	Protein/Organism/Length	Residues/Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAB58156	Lung cancer associated	48 . . . 431	208/384 (54%)	e−124
	polypeptide sequence SEQ ID	28 . . . 411	277/384 (71%)
	494 - Homo sapiens, 430 aa.
	[WO200055180-A2,
	21 SEP. 2000]
ABB66868	Drosophila melanogaster	1 . . . 394	199/394 (50%)	e−115
	polypeptide SEQ ID NO	1 . . . 394	270/394 (68%)
	27396 - Drosophila
	melanogaster, 561 aa.
	[WO200171042-A2,
	27 SEP. 2001]
ABB65492	Drosophila melanogaster	1 . . . 394	199/394 (50%)	e−115
	polypeptide SEQ ID NO	1 . . . 394	270/394 (68%)
	23268 - Drosophila
	melanogaster, 561 aa.
	[WO200171042-A2,
	27 SEP. 2001]
AAG21988	Arabidopsis thaliana protein	2 . . . 445	210/449 (46%)	e−112
	fragment SEQ ID NO: 24747 -	10 . . . 456	288/449 (63%)
	Arabidopsis thaliana, 484
	aa. [EP1033405-A2,
	06 SEP. 2000]
AAG11789	Arabidopsis thaliana protein	2 . . . 445	210/449 (46%)	e−112
	fragment SEQ ID NO: 10644 -	10 . . . 456	288/449 (63%)
	Arabidopsis thaliana, 484
	aa. [EP1033405-A2,
	06 SEP. 2000]

[0371] 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
Accession		NOV4a Residues/	for the
Number	Protein/Organism/Length	Match Residues	Matched Portion	Expect Value
P30838	Aldehyde dehydrogenase,	1 . . . 453	453/453 (100%)	0.0
	dimeric NADP-preferring (EC	1 . . . 453	453/453 (100%)
	1.2.1.5) (ALDH class 3)
	(ALDHIII) - Homo sapiens
	(Human), 453 aa.
Q9BT37	Aldehyde dehydrogenase 3	1 . . . 453	452/453 (99%)	0.0
	(Aldehyde dehydrogenase 3	1 . . . 453	452/453 (99%)
	family, member Al) - Homo
	sapiens (Human), 453 aa.
A42584	aldehyde dehydrogenase	1 . . . 453	450/453 (99%)	0.0
	(NAD(P)+) (EC 1.2. 1.5) 3 -	1 . . . 453	451/453 (99%)
	human, 453 aa.
A30149	aldehyde dehydrogenase	1 . . . 453	370/453 (81%)	0.0
	(NADP+) (EC 1.2.1.4) 3,	1 . . . 453	415/453 (90%)
	tumor-associated [similarity] -
	rat, 453 aa.
P11883	Aldehyde dehydrogenase,	2 . . . 453	369/452 (81%)	0.0
	dimeric NADP-preferring (EC	1 . . . 452	414/452 (90%)
	1.2.1.5) (ALDH class 3)
	(Tumor-associated aldehyde
	dehydrogenase)
	(HTC-ALDH) - Rattus
	norvegicus (Rat), 452 aa.

[0372] PFam analysis predicts that the NOV4a protein contains the domains shown in the Table 4F.

TABLE 4F
Domain Analysis of NOV4a
			Identities/
		NOV4a	Similarities
	Pfam	Match	for the	Expect
	Domain	Region	Matched Region	Value
	aldedh	1 . . . 432	182/492 (37%)	7.4e−206
			401/492 (82%)

Example 5

[0373] 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: 29	2316 bp
NOV5a,	GCCACGAAGGCCACAGACGCCTTCCCCCTTGGACTCTCATTCCCTTTTCCACGGAGCCCCGCGCTTTC
GC140468-01
DNA Sequence	GTGAGCCCCCTCGAGGAACCTGGTCTCCGCATCCAGTTACCACCTCCTGCCTCAGAGGCCATCTGAGC
	CCTTCGCACCTCGCCCCTCAGTCCCCCCTTGCCCCCCCGCGGAGATCGCCTCGCTCCCTCCCGCCCCC
	CCATCATCCCTTCCCTCGCAGTTCCCCTGTCCTGAGGGGAGCCCCGCCACGGCAGCGACAGCGGGCAG
	GAGGGAGAAAGTGAAGGTTGGGCGACACTTGGCCTCACTCCCGGCTAGGCGCACCCACGGGGAGGAGA
	GGAGGAGCCGAGAGAGCTGAGCAGCGCGGAAGTAGCTGCTGCTGGTGGTGACAATGTCAAATAACGGC
	CTAGACATTCAAGACAAACCCCCAGCCCCTCCGATGAGAAATACCAGCACTATGATTGGAGTCGGCAG
	CAAAGATGCTGGAACCCTAAACCATGGTTCTAAACCTCTGCCTCCAAACCCAGAGGAGAAGAAAAAGA
	AGGACCGATTTTACCGATCCATTTTACCTGGAGATAAAACAAATAAAAAGAAAGAGAAAGAGCGGCCA
	GAGATTTCTCTCCCTTCAGATTTTGAACACACAATTCATGTCCGTTTTGATGCTGTCACAGGGGAGTT
	TACGGGAATGCCAGAGCAGTGGGCCCGCTTGCTTCAGACATCAAATATCACTAAGTCGGAGCAGAAGA
	AAAACCCGCAGGCTGTTCTGGATGTGTTGGAGTTTTACAACTCGAAGAAGACATCCAACAGCCAGAAA
	TACATGAGCTTTACAGATAAGTCAGCTGAGGATTACAATTCTTCTAATGCCTTGAATGTGAAGGCTGT
	GTCTGAGACTCCTGCAGTGCCACCAGTTTCAGAAGATGAGGATGATGATGATGATGATGCTACCCCAC
	CACCAGTGATTGCTCCACGCCCAGAGCACACAAAATCTGTATACACACGGTCTGTGATTGAACCACTT
	CCTGTCACTCCAACTCGGGACGTGGCTACATCTCCCATTTCACCTACTGAAAATAACACCACTCCACC
	AGATGCTTTGACCCGGAATACTGAGAAGCAGAAGAAGAAGCCTAAAATGTCTGATGAGGAGATCTTGG
	AGAAATTACGAAGCATAGTGAGTGTGGGCGATCCTAAGAAGAAATATACACGGTTTGAGAAGATTGGA
	CAAGGTGCTTCAGGCACCGTGTACACAGCAATGGATGTGGCCACAGGACAGGAGGTGGCCATTAAGCA
	GATGAATCTTCAGCAGCAGCCCAAGAAAGAGCTGATTATTAATGAGATCCTGGTCATGAGGGAAAACA
	AGAACCCAAACATTGTGAATTACTTGGACAGTTACCTCGTGGGAGATGAGCTGTGGGTTGTTATGGAA
	TACTTGGCTGGAGGCTCCTTGACAGATGTGGTGACAGAAACTTGCATGGATGAAGGCCAAATTGCAGC
	TGTGTGCCGTGAGTGTCTGCAGGCTCTGGAGTTCTTGCATTCGAACCAGGTCATTCACAGAGACATCA
	AGAGTGACAATATTCTGTTGGGAATGGATGGCTCTGTCAAGCTAACTGACTTTGGATTCTGTGCACAG
	ATAACCCCAGAGCAGAGCAAACGGAGCACCATGGTAGGAACCCCATACTGGATGGCACCAGAGGTTGT
	GACACGAAAGGCCTATGGGCCCAAGGTTGACATCTGGTCCCTGGGCATCATGGCCATCGAAATGATTG
	AAGGGGAGCCTCCATACCTCAATGAAAACCCTCTGAGAGCCTTGTACCTCATTGCCACCAATGGGACC
	CCAGAACTTCAGAACCCAGAGAAGCTGTCAGCTATCTTCCGGGACTTTCTGAACCGCTGTCTCGATAT
	GGATGTGGAGAAGAGAGGTTCAGCTAAAGAGCTGCTACAGCATCAATTCCTGAAGATTGCCAAGCCCC
	TCTCCAGCCTCACTCCACTGATTGCTGCAGCTAAGGAGGCAACAAAGAACAATCACTAAAACCACACT
	CACCCCAGCCTCATTGTGCCAAGCTCTGTGAGATAAATGCACATTTCAGAAATTCCAACTCCTGATGC
	CCTCTTCTCCTTGCCTTGCTTCTCCCATTTCCTGATCTAGCACTCCTCAAGACTTTGATCCTTGGAAA
	CCGTGTGTCCAGCATTGAAGAGAACTGCAACTGAATGACTAATCAGATGATGGCCATTTCTAAATAAG
	GAATTTCCTCCCAATTCATGGATATGAGGGTGGTTTATGATTAAGGGTTTATATAAATAAATGTTTCT
	AGTC
	ORF Start: ATG at 394		ORF Stop: TAA at 2029
	SEQ ID NO: 30	545 aa	MW at 60660.3kD
NOV5a,	MSNNGLDIQDKPPAPPMRNTSTMIGVGSKDAGTLNHGSKPLPPNPEEKKKKDRFYRSILPGDKTNKKK
CG140468-01
Protein	EKERPEISLPSDFEHTIHVGFDAVTGEFTGMPEQWARLLQTSNITYSEQKKNPQAVLDVLEFYNSKKT
Sequence
	SNSQKYMSFTDKSAEDYNSSNALNVKAVSETPAVPPVSEDEDDDDDDATPPPVIAPRPEHTKSVYTRS
	VIEPLPVTPTRDVATSPISPTENNTTPPDALTRNTEKQKKKPKMSDEEILEKLRSIVSVGDPKKKYTR
	FEKIGQGASGTVYTAMDVATGQEVAIKQMNLQQQPKKELIINEILVMRENKNPNIVNYLDSYLVGDEL
	WVVMEYLAGGSLTDVVTETCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDF
	GFCAQITPEQSKRSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMIEGEPPYLNENPLRALYLI
	ATNGTPELQNPEKLSAIFRDFLNRCLDMDVEKRGSAKELLQHQFLKIAKPLSSLTPLIAAAKEATKNN
	H
	SEQ ID NO: 31	957 bp
NOV5b,	GACAATGTCAAATAACGGCCTAGACATTCAAGACAAACCCCCAGCCCCTCCGATGAGAAATACCAGC
CG140468-02
DNA Sequence	ACTATGATTGGAGCCGGCAGCAAAGATGCTGGAACCCTAAACCATGGTTCTAAACCTCTGCCTCCAA
	ACCCAGAGGAGAAGAAAAAGAAGGACCGATTTTACCGATCCATTTTACCTGGAGATAAAACAAATAA
	AAAGAAAGAGAAAGAGCGGCCAGAGATTTCTCTCCCTTCAGATTTTGAACACACAATTCATGTCGGT
	TTTGATGCTGTCACAGGGGAGTTTACGGGAATGCCAGAGCAGTGGGCCCGCTTGCTTCAGACATCAA
	ATATCACTAAGTCGGAGCAGAAGAAAAACCCGCAGGCTGTTCTGGATGTGTTGGAGTTTTACAACTC
	GAAGAAGACATCCAACAGCCAGAAATACATGAGCTTTACAGATAAGTCAGCTGAGGATTACAATTCT
	TCTAATGCCTTGAATGTGAAGGCTGTGTCTGAGACTCCTGCAGTGCCACCAGTTTCAGAAGATGAGG
	ATGATGATGATGATGATGCTACCCCACCACCAGTGATTGCTCCACGCCCAGAGCACACAAAATCTGT
	ATACACACGGTCTGTGATTGAACCACTTCCTGTCACTCCAACTCGGGACGTGGCTACATCTCCCATT
	TCACCTACTGAAAATAACACCACTCCACCAGATGCTTTGACCCGGAATACTGAGAAGCAGAAGAAGA
	AGCCTAAAATGTCTGATGAGGAGATCTTGGAGAAATTACGAAGCATAGTGAGTGTGGGCGATCCTAA
	GAAGAAATATACACGGTTTGAGAAGATTGCCAAGCCCCTCTCCAGCCTCACTCCACTGATTGCTGCA
	GCTAAGGAGGCAACAAAGAACAATCACTAAAACCACACTCACCCCAGCCTCATTGTGCCAAGCCTTC
	TGTGAGATAAATGCACATT
	ORF Start: ATG at 5		ORF Stop: TAA at 899
	SEQ ID NO: 32	298 aa	MW at 32989.7kD
NOV5b,	MSNNGLDIQDKPPAPPMRNTSTMIGAGSKDAGTLNHGSKPLPPNPEEKKKKDRFYRSILPGDKTNKK
CG140468-02
Protein	KEKERPEISLPSDFEHTIHVGFDAVTGEFTGMPEQWARLLQTSNITKSEQKKNPQAVLDVLEFYNSK
Sequence
	KTSNSQKYMSFTDKSAEDYNSSNALNVKAVSETPAVPPVSEDEDDDDDDATPPPVIAPRPEHTKSVY
	TRSVIEPLPVTPTRDVATSPISPTENNTTPPDALTRNTEKQKKKPKMSDEEILEKLRSIVSVGDPKK
	KYTRFEKIAKPLSSLTPLIAAAKEATKNNH

[0374] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 5B.

TABLE 5B
Comparison of NOV5a against NOV5b.
		Identities/
		Similarities
	NOV5a Residues/	for the
Protein Sequence	Match Residues	Matched Region
NOV5b	1 . . . 281	238/281 (84%)
	1 . . . 281	239/281 (84%)

[0375] Further analysis of the NOVSa protein yielded the following properties shown in Table 5C.

TABLE 5C
Protein Sequence Properties NOV5a
PSort analysis:   0.7000 probability located in nucleus; 0.3000
                  probability located in microbody (peroxisome);
                  0.1000 probability located in mitochondrial
                  matrix space; 0.1000 probability located in
                  lysosome (lumen)
SignalP analysis: No Known Signal Sequence Predicted

[0376] 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
Geneseq	Protein/Organism/Length	NOV5a Residues/	for the Matched	Expect
Identifier	[Patent #, Date]	Match Residues	Region	Value
AAB03968	p-21 activated protein kinase	1 . . . 545	544/545 (99%)	0.0
	(PAK1) - Homo sapiens, 545	1 . . . 545	545/545 (99%)
	aa. [WO200060062-A2,
	12 OCT. 2000]
AAY55958	Human STE20-related	1 . . . 545	541/545 (99%)	0.0
	protein kinase PAK1_h -	1 . . . 545	542/545 (99%)
	Homo sapiens, 545 aa.
	[W09953036-A2,
	21 OCT. 1999]
ABG30251	Novel human diagnostic	1 . . . 542	474/556 (85%)	0.0
	protein #30242 - Homo	7 . . . 557	500/556 (89%)
	sapiens, 587 aa.
	[WO200175067-A2,
	11 OCT. 2001]
AAW72757	Human doublin - Homo	3 . . . 544	444/552 (80%)	0.0
	sapiens, 544 aa.	2 . . . 542	489/552 (88%)
	[WO9840495-A1,
	17 SEP. 1998]
ABB57290	Mouse ischaemic condition	3 . . . 544	441/552 (79%)	0.0
	related protein sequence SEQ	2 . . . 542	483/552 (86%)
	ID NO: 817 - Mus musculus,
	544 aa. [WO200188188-A2,
	22 NOV. 2001]

[0377] 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
Accession		NOV5a Residues/	for the	Expect
Number	Protein/Organism/Length	Match Residues	Matched Portion	Value
Q13153	Serine/threonine-protein	1 . . . 545	545/545 (100%)	0.0
	kinase PAK1 (EC 2.7.1.-)	1 . . . 545	545/545 (100%)
	(p21-activated kinase 1)
	(PAK-1) (P65-PAK)
	(Alpha-PAK) - Homo sapiens
	(Human), 545 aa.
P35465	Serine/threonine-protein	1 . . . 545	537/545 (98%)	0.0
	kinase PAK1 (EC 2.7.1.-)	1 . . . 544	539/545 (98%)
	(p21-activated kinase 1)
	(PAK-1) (P68-PAK)
	(Alpha-PAK) (Protein kinase
	MUK2) - Rattus norvegicus
	(Rat), 544 aa.
S40482	serine/threonine-specific	1 . . . 545	534/545 (97%)	0.0
	protein kinase (EC 2.7.1.-) -	1 . . . 544	537/545 (97%)
	rat, 544 aa.
O88643	Serine/threonine-protein	1 . . . 545	530/545 (97%)	0.0
	kinase PAK1 (EC 2.7.1.-)	1 . . . 545	537/545 (98%)
	(p21-activated kinase 1)
	(PAK-1) (P65-PAK)
	(Alpha-PAK) (CDC42/RAC
	effector kinase PAK-A) - Mus
	musculus (Mouse), 545 aa.
O75561	P21 activated kinase 1B -	1 . . . 522	517/522 (99%)	0.0
	Homo sapiens (Human), 553	1 . . . 522	520/522 (99%)
	aa.

[0378] PFam analysis predicts that the NOV5a protein contains the domains shown in the Table 5F.

TABLE 5F
Domain Analysis of NOV5a
		Identities/
		Similarities
	NOV5a Match	for the Matched	Expect
Pfam Domain	Region	Region	Value
PBD	75 . . . 135	37/64 (58%)	3.4e−34
		59/64 (92%)
pkinase	270 . . . 521	94/291 (32%)	5.7e−90
		208/291 (71%)

Example 6

[0379] 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: 33	3255 bp
NOV6a,	GACAGCTTTGGGTGGACCAGTAATGAGGAAATGAGGCAACATGATGTGCAGGAACTGAATCGAATCCT
CG142182-01
DNA Sequence	CTTCAGCGCTTTGGAAACTTCTTTAGTTGGGACCTCCGGTCATGACCTCATCTATCGTCTGTACCATG
	GAACCATTGTTAACCAGATTGTTTGTAAAGAATGTAAGAACGTTAGCGAGAGGCAGGAAGACTTCTTA
	GATCTAACAGTAGCAGTCAAAAATGTATCCGGTTTGGAAGATGCTCTCTGGAACATGTATGTAGAAGA
	GGAAGTTTTTGATTGTGACAACTTGTACCACTGTGGAACTTGTGACAGGCTGGTTAAAGCAGCAAAGT
	CGGCCAAATTACGTAAGCTGCCTCCTTTTCTTACTGTTTCATTACTAAGATTTAATTTTGATTTTGTG
	AAATGCGAACGCTACAAGGAAACTAGCTGTTATACATTCCCTCTCCGGATTAATCTCAAGCCCTTTTG
	TGAACAGAGTGAATTGGATGACTTAGAATATATATATGACCTCTTCTCAGTTATTATACACAAAGGTG
	GCTGCTACGGAGGCCATTACCATGTATATATTAAAGATGTTGATCATTTGGGAAACTGGCAGTTTCAA
	GAGGAAAAAAGTAAACCAGATGTGAATCTGAAAGATCTCCAGAGTGAAGAAGAGATTGATCATCCACT
	GATGATTCTAAAAGCAATCTTATTAGAGGAGGAGAATAATCTAATTCCTGTTGATCAGCTGGGCCAGA
	AACTTTTGAAAAAGATAGGAATATCTTGGAACAAGAAGTACAGAAAACAGCATGGACCATTGCGGAAG
	TTCTTACAGCTCCATTCTCAGATATTTCTACTCAGTTCAGATGAAAGTACAGTTCGTCTCTTGAAGAA
	TAGTTCTCTCCAGGCTGAGTCTGATTTCCAAAGGAATGACCAGCAAATTTTCAAGATGCTTCCTCCAG
	AATCCCCAGGTTTAAACAATAGCATCTCCTGTCCCCACTGGTTTGATATAAATGATTCTAAAGTCCAG
	CCAATCAGGGAAAAGGATATTGAACAGCAATTTCAGGGTAAAGAAAGTGCCTACATGTTGTTTTATCG
	GAAATCCCAGTTGCAGAGACCCCCTGAAGCTCGAGCTAATCCAAGATATGGGGTTCCATGTCATTTAC
	TGAATGAAATGGATGCAGCTAACATTGAACTGCAAACCAAAAGGGCAGAATGTGATTCTGCAAACAAT
	ACTTTTGAATTGCATCTTCACCTGGGCCCTCAGTATCATTTCTTCAATGGGGCTCTGCACCCAGTAGT
	CTCTCAAACAGAAAGCGTGTGGGATTTGACCTTTGATAAAAGAAAAACTTTAGGAGATCTCCGGCAGT
	CAATATTTCAGCTGTTAGAATTTTGGGAAGGAGACATGGTTCTTAGTGTTGCAAAGCTTGTACCAGCA
	GGACTTCACATTTACCAGTCACTTGGCGGGGATGAACTGACACTGTGTGAAACTGAAATTGCTGATGG
	GGAAGACATCTTTGTGTGGAATGGGGTGGAGGTTGGTGGAGTCCACATTCAAACTGGTATTGACTGCG
	AACCTCTACTTTTAAATGTTCTTCATCTAGACACAAGCAGTGATGGAGAAAAGTGTTGTCAGGTGATA
	GAATCTCCACATGTCTTTCCAGCTAATGCAGAAGTGGGCACTGTCCTCAACGCCTTAGCAATCCCAGC
	AGGTGTCATCTTCATCAACAGTGCTGGATGTCCAGGTGGGGAGGGTTGGACGGCCATCCCCAAGGAAG
	ACATGAGGAAGACGTTCAGGGAGCAAGGGCTCAGAAATGGAAGCTCAATTTTAATTCAGGATTCTCAT
	GATGATAACAGCTTGTTGACCAAGGAAGAGAAATGGGTCACTAGTATGAATGAGATTGACTGGCTCCA
	CGTTAAAAATTTATGCCAGTTAGAATCTGAAGAGAAGCAAGTTAAAATATCAGCAACTGTTAACACAA
	TGGTGTTTGATATTCGAATTAAAGCCATAAAGGAATTAAAATTAATGAAGGAACTAGCTGACAACAGC
	TGTTTGAGACCTATTGATAGAAATGGGAAGCTTCTTTGTCCAGTGCCGGACAGCTATACTTTGAAGGA
	AGCAGAATTGAAGATGGGAAGTTCATTGGGACTGTGTCTTGGAAAAGCACCAAGTTCGTCTCAGTTGT
	TCCTGTTTTTTGCAATGGGGAGTGACGTTCAACCTGGGACAGAAATGGAAATCGTAGTAGAAGAAACA
	ATATCTGTGAGAGATTGTTTAAAGTTAATGCTGAAGAAATCTGGCCTACAAGACTCCTTTATAGGAGA
	TGCCTGGCATTTACGAAAAATGGATTGGTGCTATGAAGCTGGAGAGCCTTTATGTGAAGAAGATGCAA
	CACTGAAAGAACTTCTGATATGTTCTGGAGATACTTTGCTTTTAATTGAAGGACAACTTCCTCCTCTG
	GGTTTCCTGAAGGTGCCCATCTGGTGGTACCAGCTTCAGGGTCCCTCAGGACACTGGGAGAGTCATCA
	GGACCAGACCAACTGTACTTCGTCTTGGGGCAGAGTTTGGAGAGCCACTTCCAGCCAAGGTGCTTCTG
	GGAACGAGCCTGCGCAAGTTTCTCTCCTCTACTTGGGAGACATAGAGATCTCAGAAGATGCCACGCTG
	GCGGAGCTGAAGTCTCAGGCCATGACCTTGCCTCCTTTCCTGGAGTTCGGTGTCCCGTCCCCAGCCCA
	CCTCAGAGCCTGGACGGTGGAGAGGAAGCGCCCAGGCAGGCTTTTACGAACTGACCGGCAGCCACTCA
	GGGAATATAAACTAGGACGGAGAATTGAGATCTGCTTAGAGCCCCTTCAGAAAGGCGAAAACTTGGGC
	CCCCAGGACGTGCTGCTGAGGACACAGGTGCGCATCCCTGGTGAGAGGACCTATGCCCCTGCCCTGGA
	CCTGGTGTGGAACGCGGCCCAGGGTGGGACTGCCGGCTCCCTGAGGCAGAGAGTTGCCGATTTCTATT
	GTCTTCCCGTGGAGAAGATTGAAATTGCCAAATACTTTCCCGAAAAGTTCGAGTGGCTTCCGATATCT
	AGCTGGAACCAACAAATAACCAAGAGGAAAAAAAAAAAAAAACAAGATTATTTGCAAGGGGCACCGTA
	TTACTTGAAAGACGGAGATACTATTGGTGTTAAGGTAAGTTGTTTAACAGCAAATTTACCACTTTGAG
	AAGACACGAGGGTCACATGATTTTATAGAGACGTTTTATTGAATCTTCAAGACACAGAT
	ORF Start: ATG at 31		ORF Stop: TGA at 3193
	SEQ ID NO: 34	1054 aa	MW at 119613.5 kD
NOV6a,	MRQHDVQELNRILFSALETSLVGTSGHDLIYRLYHGTIVNQIVCKECKNVSERQEDFLDLTVAVKNVS
CG142182-01
Protein	GLEDALWNMYVEEEVFDCDNLYHCGTCDRLVKAAKSAKLRKLPPFLTVSLLRFNFDFVKCERYKETSC
Sequence
	YTFPLRINLKPFCEQSELDDLEYIYDLFSVIIHKGGCYGGHYHVYIKDVDHLGNWQFQEEKSKPDVNL
	KDLQSEEEIDHPLMILKAILLEEENNLIPVDQLGQKLLKKIGISWNKKYRKQHGPLRKFLQLHSQIFL
	LSSDESTVRLLKNSSLQAESDFQRNDQQIFKMLPPESPGLNNSISCPHWFDINDSKVQPIREKDIEQQ
	FQGKESAYMLFYRKSQLQRPPEARANPRYGVPCHLLNEMDAANIELQTKRAECDSANNTFELHLHLGP
	QYHFFNGALHPVVSQTESVWDLTFDKRKTLGDLRQSIFQLLEFWEGDMVLSVAKLVPAGLHIYQSLGG
	DELTLCETEIADGEDIFVWNGVEVGGVHIQTGIDCEPLLLNVLHLDTSSDGEKCCQVIESPHVFPANA
	EVGTVLTALAIPAGVIFINSAGCPGGEGWTAIPKEDMRKTFREQGLRNGSSILIQDSHDDNSLLTKEE
	KWVTSMNEIDWLHVKNLCQLESEEKQVKISATVNTMVFDIRIKAIKELKLMKELADNSCLRPIDRNGK
	LLCPVPDSYTLKEAELKMGSSLGLCLGKAPSSSQLFLFFAMGSDVQPGTEMEIVVEETISVRDCLKLM
	LKKSGLQDSFIGDAWHLRKMDWCYEAGEPLCEEDATLKELLICSGDTLLLIEGQLPPLGFLKVPIWWY
	QLQGPSGHWESHQDQTNCTSSWGRVWRATSSQGASGNEPAQVSLLYLGDIEISEDATLAELKSQAMTL
	PPFLEFGVPSPAHLRAWTVERKRPGRLLRTDRQPLREYKLGRRIEICLEPLQKGENLGPQDVLLRTQV
	RIPGERTYAPALDLVWNAAQGGTAGSLRQRVADFYCLPVEKIEIAKYFPEKFEWLPISSWNQQITKRK
	KKKKQDYLQGAPYYLKDGDTIGVKVSCLTANLPL

[0380] Further analysis of the NOV6a protein yielded the following properties shown in Table 6B.

TABLE 6B
Protein Sequence Properties NOV6a
PSort analysis:   0.7000 probability located in plasma membrane;
                  0.3500 probability located in nucleus; 0.3000
                  probability located in microbody (peroxisome);
                  0.2000 probability located in endoplasmic
                  reticulum (membrane)
SignalP analysis: No Known Signal Sequence Predicted

[0381] 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
Geneseq	Protein/Organism/Length	NOV6a Residues/	for the	Expect
Identifier	[Patent #, Date]	Match Residues	Matched Region	Value
AAE14346	Human protease PRTS-11	1 . . . 1044	1037/1044 (99%)	0.0
	protein - Homo sapiens,	1 . . . 1040	1037/1044 (99%)
	1108 aa.
	[WO200183775-A2,
	08 NOV. 2001]
AAU68535	Human novel cytokine	1 . . . 1044	1037/1044 (99%)	0.0
	encoded by cDNA	129 . . . 1167	1038/1044 (99%)
	790CIP2C_6 #1 - Homo
	sapiens, 1346 aa.
	[WO200175093-A1,
	11 OCT. 2001]
AAB93169	Human protein sequence	1 . . . 1019	1013/1019 (99%)	0.0
	SEQ ID NO: 12102 - Homo	1 . . . 1014	1013/1019 (99%)
	sapiens, 1014 aa.
	[EP1074617-A2,
	07 FEB. 2001]
AAU68534	Human novel cytokine	1 . . . 1044	1015/1044 (97%)	0.0
	encoded by cDNA	129 . . . 1145	1015/1044 (97%)
	790CIP2C_5 #1 - Homo
	sapiens, 1324 aa.
	[WO200175093-A1,
	11 OCT. 2001]
ABG27066	Novel human diagnostic	500 . . . 666	166/168 (98%)	4e−91
	protein #27057 - Homo	47 . . . 214	166/168 (98%)
	sapiens, 674 aa.
	[WO200175067-A2,
	11 OCT. 2001]

[0382] 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
Accession		NOV6a Residues/	for the	Expect
Number	Protein/Organism/Length	Match Residues	Matched Portion	Value
Q9NVE5	CDNA FLJ10785 fis, clone	1 . . . 1019	1013/1019 (99%)	0.0
	NT2RP4000457, weakly	1 . . . 1014	1013/1019 (99%)
	similar to ubiquitin
	carboxyl-terminal hydrolase
	15 (EC 3.1.2.15) - Homo
	sapiens (Human), 1014 aa
	(fragment).
Q95KB6	Hypothetical 102.2 kDa	143 . . . 1024	844/882 (95%)	0.0
	protein - Macaca fascicularis	30 . . . 907	860/882 (96%)
	(Crab eating macaque)
	(Cynomolgus monkey), 907
	aa (fragment).
Q8S1J6	Putative ubiquitin	3 . . . 342	102/359 (28%)	3e−23
	carboxyl-terminal hydrolase -	223 . . . 568	165/359 (45%)
	Oryza sativa (japonica
	cultivar-group), 1079 aa.
Q8VZM4	Putative ubiquitin	3 . . . 202	72/205 (35%)	3e−23
	carboxyl-terminal hydrolase -	278 . . . 480	105/205 (51%)
	Arabidopsis thaliana
	(Mouse-ear cress), 683 aa.
Q94ED6	Putative ubiquitin	3 . . . 342	102/359 (28%)	3e−23
	carboxyl-terminal hydrolase -	273 . . . 618	165/359 (45%)
	Oryza sativa (Rice), 1108
	aa.

[0383] PFam analysis predicts that the NOV6a protein contains the domains shown in the Table 6E.

TABLE 6E
Domain Analysis of NOV6a
			Identities/
			Similarities
	Pfam	NOV6a Match	for the	Expect
	Domain	Region	Matched Region	Value
	UCH-2	157 . . . 354	23/203 (11%)	0.00033
			141/203 (69%)

Example 7

[0384] 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: 35	692 bp
NOV7a,	GACAGGAGTGAACCCGAGCTGTGCCGACCAACCCCCAGGATGGCGGAAGCTCACCAGGCCGTGGCCTT
CG142564-01
DNA Sequence	CCAGTTCACGGTGACCCCAGACGGGGTCGACTTCCGGCTCAGTCGGGAGGCCCTGAAACACGTCTACC
	TGTCTGGGATCAACTCCTGGAAGAAACGCCTGATCCGCATCAAGAATGGCATCCTCAGGGGCGTGTAC
	CCTGGCAGCCCCACCAGCTGGCTGGTCGTCATCATGGTAACAGTGGGTTCCTCCTTCTGCAACGTGGA
	CATCTCCTTGGGGCTGGTCAGTTGCATCCAGAGATGCCTCCCTCAGGGGTGTGGCCCCTACCAGACCC
	CGCAGACCCGGGCACTTCTCAGCATGGCCATCTTCTCCACGGGCGTCTGGGTGACGGGCATCTTCTTC
	TTCCGCCAAACCCTGAAGCTGCTTCTCTGCTACCAATCCCAGATCCGCATGTTCGACCCAGAGCAGCA
	CCCCAATCACCTGGGCGCTGGAGGTGGCTTTGGCCCTGTAGCAGATGATGGCTATGGAGTTTCCTACA
	TGATTGCAGGCGAGAACACGATCTTCTTCCACATCTCCAGCAAGTTCTCAAGCTCAGAGACGAACGCC
	CAGCGCTTTGGAAACCACATCCGCAAAGCCCTGCTGGACATTGCTGATCTTTTCCAAGTTCCTCAGGC
	CTACAGCTGAAG
	ORF Start: ATG at 40		ORF Stop: TGA at 688
	SEQ ID NO: 36	216 aa	MW at 23874.3kD
NOV7a,	MAEAHQAVAFQFTVTPDGVDFRLSREALKHVYLSGINSWKKRLIRIKNGILRGVYPGSPTSWLVVIMV
CG142564-01
Protein	TVGSSFCNVDISLGLVSCIQRCLPQGCGPYQTPQTRALLSMAIFSTGVWVTGIFFFRQTLKLLLCYQS
Sequence
	QIRMFDPEQHPNHLGAGGGFGPVADDGYGVSYMIAGENTIFFHISSKFSSSETNAQRFGNHIRKALLD
	IADLFQVPQAYS

[0385] Further analysis of the NOV7a protein yielded the following properties shown in Table 7B.

TABLE 7B
Protein Sequence Properties NOV7a
PSort analysis:   0.7900 probability located in plasma membrane;
                  0.6400 probability located in microbody
                  (peroxisome); 0.3000 probability located in
                  Golgi body; 0.2000 probability located in
                  endoplasmic reticulum (membrane)
SignalP analysis: Cleavage site between residues 5 and 6

[0386] A search of the NOV7a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 7C.

TABLE 7C
Geneseq Results for NOV7a
		NOV7a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAW14438	Type I carnitine palmitoyl	1 . . . 134	131/134 (97%)	4e−72
	transferase-like protein -	1 . . . 134	131/134 (97%)
	Homo sapiens, 772 aa.
	[JP09009969-A,
	14 JAN. 1997]
AAE10322	Human carnitine	1 . . . 134	57/134 (42%)	1e−21
	acyltransferase, 26886 -	1 . . . 132	78/134 (57%)
	Homo sapiens, 803 aa.
	[WO200166759-A2,
	13 SEP. 2001]
AAY79220	Human transferase	1 . . . 134	57/134 (42%)	1e−21
	TRNSFS-12 - Homo sapiens,	1 . . . 132	78/134 (57%)
	803 aa. [WO200014251-A2,
	16 MAR. 2000]
ABB67527	Drosophila melanogaster	137 . . . 210	43/74 (58%)	6e−19
	polypeptide SEQ ID NO	688 . . . 761	55/74 (74%)
	29373 - Drosophila
	melanogaster, 780 aa.
	[WO200171042-A2,
	27 SEP. 2001]
ABB66942	Drosophila melanogaster	137 . . . 210	43/74 (58%)	6e−19
	polypeptide SEQ ID NO	690 . . . 763	55/74 (74%)
	27618 - Drosophila
	melanogaster, 782 aa.
	[WO200171042-A2,
	27 SEP. 2001]

[0387] In a BLAST search of public sequence datbases, the NOV7a protein was found to have homology to the proteins shown in the BLASTP data in Table 7D.

TABLE 7D
Public BLASTP Results for NOV7a
			Identities/
Protein			Similarities for
Accession		NOV7a Residues/	the Matched	Expect
Number	Protein/Organism/Length	Match Residues	Portion	Value
Q9BY90	KIAA1670 protein - Homo	1 . . . 134	133/134 (99%)	2e−73
	sapiens (Human), 598 aa	18 . . . 151	133/134 (99%)
	(fragment).
Q92523	Carnitine	1 . . . 134	133/134 (99%)	2e−73
	O-palmitoyltransferase I,	1 . . . 134	133/134 (99%)
	mitochondrial muscle isoform
	(EC 2.3.1.21) (CPT I)
	(CPTI-M) (Carnitine
	palmitoyltransferase I like
	protein) - Homo sapiens
	(Human), 772 aa.
Q924X2	Muscle-type carnitine	1 . . . 149	118/149 (79%)	1e−63
	palmitoyltransferase I (EC	1 . . . 147	128/149 (85%)
	2.3.1.21) (Hypothetical 88.2
	kDa protein) - Mus musculus
	(Mouse), 772 aa.
O35287	Carnitine palmitoyltransferase	1 . . . 149	118/149 (79%)	1e−63
	I - Mus musculus (Mouse),	1 . . . 147	128/149 (85%)
	772 aa.
Q9QYP4	Muscle type carnitine	1 . . . 149	118/149 (79%)	1e−63
	palmitoyltransferase I - Mus	1 . . . 147	128/149 (85%)
	musculus (Mouse), 772 aa.

Example 8

[0388] 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:37	1122 bp
NOV8a,	CTAGATTTTTGAAACATGAATCCTTCACTCCTCCTGGCTGCCTTTTTCCTGGGAATTGCCTCAGCTGC
CG142797-01
DNA Sequence	TCTAACACGTGACCACAGTCTAGACGCACAATGGACCAAGTGGAAGGCAAAGCACAAGAGATTATATG
	ACATGGAGAACATGAAGATGACTGAGCAGCACAATCAGGAATACAGCCAAGGGAAACACAGCTTCACA
	ATGGCCATGAACACCTTTGGAGACATGACCACTGAAGAATTCAGGCAGGTGATGAATGGTTTTCAATA
	CCAGAAGCACAGGAACGGGAAACAGTTCCAGGAACGCCTGCTTCTTGAGATCCCCACATCTGTGGACT
	GGAGAGAGAAAGGCTACATGACTCCTGTGAAGGATCAGGGTCAGTGTGGCTCTTGTTGGGCTTTTAGT
	GCAACTGGTGCTCTGGAAGGGCAGATGTTCTGGAAAACAGGCAAACTTATCTCACTGAATGAGCAGAA
	TCTGGTAGACTGCTCTGGGCCTCAAGGCAATGAGGGCTGCAATGGTGGCTTCATGGATAATCCCTTCC
	GGTATGTTCAGGAGAACGGAGGCCTGGACTCTGAGGCATCCTATCCATATGAAAAAACCTGTAGGTAC
	AATCCCAAGTATTCTGCTGCTAATGACACTGGCTTTGTGGACATCCCTTCACAGGAGAAGGACCTGGC
	GAAGGCAGTGGCAACTGTGGGGCCCATCTCTGTTGCTGCTGGTGCAAGCCATGTCTCCTTCCAGTTCT
	ATAAAAAAGGTATTTATTTTGAGCCACGCTGTGACCCCGAAGGTCTGGATCATGCTATGCTGCTGGTT
	GGCTACAGCTATGAAGGAGCAGACTCAGATAACAATAAATATTGGCTGGTGAAGAACAGGTATGGTAA
	AAACTGGGGCATGGATGGCTACATAAAGATGGCCAAAGACCGGAGGAACAACTGTGGAATTGCCACAG
	CAGCCAGCTACCCCACTGTGTGAGCTGATGGATGGTGATGAGGAAGAACTTGACTGAGGATGGCACAT
	CCAAAGGAGGAATTTATCTTCAATCTACCAGCCCCTGCTGTGTGGAATGCGCACTTCAATCATTGAAG
	ATCCAAGTGTGATTGGAATTCTGATATTTTCACA
	ORF Start: ATG at 16		ORF Stop: TGA at 973
	SEQ ID NO: 38	319 aa	MW at 35984.2 kD
NOV8a,	MNPSLLLAAFFLGIASAALTRDHSLDAQWTKWKAKHKRLYDMENMKMTEQHNQEYSQGKHSFTMAMNT
CG142797-01
Protein	FGDMTTEEFRQVMNGFQYQKHRNGKQFQERLLLEIPTSVDWREKGYMTPVKDGQGCGSCWAFSATGAL
Sequence
	EGQMFWKTGKLISLNEQNLVDCSGPQGNEGCNGGFMDNPFRYVQENGGLDSEASYPYEKTCRYNPKYS
	AANDTGFVDIPSQEKDLAKAVATVGPISVAAGASHVSFQFYKKGIYFEPRCDPEGLDHAMLLVGYSYE
	GADSDNNKYWLVKNRYGKNWGMDGYIKMAKDRRNNCGIATAASYPTV

[0389] Further analysis of the NOV8a protein yielded the following properties shown in Table 8B.

TABLE 8B
Protein Sequence Properties NOV8a
PSort     0.8200 probability located in endoplasmic reticulum
analysis: (membrane); 0.5140 probability located in plasma
          membrane; 0.2423 probability located in
          microbody (peroxisome); 0.1000 probability located
          in endoplasmic reticulum (lumen)
SignalP   Cleavage site between residues 18 and 19
analysis:

[0390] 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
			Identities/
			Similarities for
Geneseq	Protein/Organism/Length	NOV8a Residues/	the Matched	Expect
Identifier	[Patent #, Date]	Match Residues	Region	Value
AAU98883	Human protease PRTS1 -	1 . . . 319	303/334 (90%)	e−180
	Homo sapiens, 334 aa.	1 . . . 334	310/334 (92%)
	[WO200238744-A2,
	16 MAY 2002]
ABG61771	Novel cathepsin-L	1 . . . 319	288/333 (86%)	e−171
	precursor-like protein - Homo	1 . . . 333	300/333 (89%)
	sapiens, 333 aa.
	[WO200229058-A2,
	11 APR. 2002]
ABG66692	Human novel polypeptide	1 . . . 319	260/333 (78%)	e−154
	#27 - Homo sapiens, 333 aa.	1 . . . 333	278/333 (83%)
	[WO200244340-A2,
	06 JUN. 2002]
ABG66714	Human novel polypeptide	1 . . . 319	259/333 (77%)	e−154
	#49 - Homo sapiens, 333 aa.	1 . . . 333	277/333 (82%)
	[WO200244340-A2,
	06 JUN. 2002]
ABB77396	Human cathepsin L - Homo	1 . . . 319	249/333 (74%)	e−147
	sapiens, 333 aa.	1 . . . 333	274/333 (81%)
	[DE10050274-A1,
	18 APR. 2002]

[0391] 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
			Identities/
Protein			Similarities for
Accession		NOV8a Residues/	the Matched	Expect
Number	Protein/Organism/Length	Match Residues	Portion	Value
P07711	Cathepsin L precursor (EC	1 . . . 319	249/333 (74%)	e−147
	3.4.22.15) (Major excreted	1 . . . 333	274/333 (81%)
	protein) (MEP) - Homo
	sapiens (Human), 333 aa.
Q9GKL8	Cysteine protease -	1 . . . 319	247/333 (74%)	e−146
	Cercopithecus aethiops (Green	1 . . . 333	273/333 (81%)
	monkey) (Grivet), 333 aa.
Q9GL24	Cathepsin L (EC 3.4.22.15) -	1 . . . 319	236/334 (70%)	e−138
	Canis familiaris (Dog), 333 aa.	1 . . . 333	265/334 (78%)
Q28944	Cathepsin L precursor (EC	1 . . . 319	228/334 (68%)	e−135
	3.4.22.15) - Sus scrofa (Pig),	1 . . . 334	263/334 (78%)
	334 aa.
P25975	Cathepsin L precursor (EC	1 . . . 319	222/334 (66%)	e−133
	3.4.22.15)- Bos taurus	1 . . . 334	261/334 (77%)
	(Bovine), 334 aa.

[0392] 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 Matched	Expect
Pfam Domain	Region	Region	Value
Peptidase_C1	103 . . . 318	123/337 (36%)	2.4e−111
		194/337 (58%)

Example 9

[0393] 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:32	1740 bp
NOV9a,	CACGAGGCCGCTAACGGTCCGGCGCCCCTCGGCGTCCGCGCGCCCCCAGCCTGGCGGACGAGCCCGGC
CG143216-01
DNA Sequence	GGCGGAGATGGGGGCGACGGGGGCGGCGGAGCCGCTGCAATCCGTGCTGTGGGTGAAGCAGCAGCGCT
	GCGCCGTGAGCCTGGAGCCCGCGCGGGCTCTGCTGCGCTGGTGGCGGAGCCCGGGGCCCGGAGCCGGC
	GCCCCCGGTGCTGATGCCTGCTCTGTGCCTGTATCTGAGATCATCGCCGTTGAGGAAACAGACGTTCA
	CGGGAAACATCAAGGCAGTGGAAAATGGCAGAAAATGGAAAAGCCTTACGCTTTTACAGTTCACTGTG
	TAAAGAGAGCACGACGGCACCGCTGGAAGTGGGCGCAGGTGACTTTCTGGTGTCCAGAGGAGCAGCTG
	TGTCACTTGTGGCTGCAGACCCTGCGGGAGATGCTGGAGAAGCTGACGTCCAGACCAAAGCATTTACT
	GGTATTTATCAACCCGTTTGGAGGAAAAGGACAAGGCAAGCGGATATATGAAAGAAAAGTGGCACCAC
	TGTTCACCTTAGCCTCCATCACCACTGACATCATCGTTACTGAACATGCTAATCAGGCCAAGGAGACT
	CTGTATGAGATTAACATAGACAAATACGACGGCATGTCTGTGTCGGCGGAGATCGGTATGTTCAGCGA
	GGTGCTGCACGGTCTGATTGGGAGGACGCAGAGGAGCGCCGGGGTCGACCAGAACCACCCCCGGGCTG
	TGCTGGTCCCCAGTAGCCTCCGGATTGGAATCATTCCCGCAGGGTCAACGGACTGCGTGTGTTACTCC
	ACCGTGGGCACCAGCGACGCAGAAACCTCGGCGCTGCATATCGTTGTTGGGGACTCGCTGGCCATGGA
	TGTGTCCTCAGTCCACCACCACAGCACACTCCTTCGCTACTCCGTGTCCCTGCTGGGCTACGGCTTCT
	ACGGGGACATCATCAAGGACAGTGAGAAGAAACGGTGGTTGGGTCTTGCCAGATACGACTTTTCAGGT
	TTAAAGACCTTCCTCTCCCACCACTGCTATGAAGGGACAGTGTCCTTCCTCCCTGCACAACACACGGT
	GGGATCTCCAAGGGATAGGAAGCCCTGCCGGGCAGGATGCTTTGTTTGCAGGCAAAGCAAGCAGCAGC
	TGGAGGAGGAGCAGAAGAAAGCACTGTATGGTTTGGAAGCTGCGGAGGACGTGGAGGAGTGGCAAGTC
	GTCTGTGGGAAGTTTCTGGCCATCAATGCCACAAACATGTCCTGTGCTTGTCGCCGGAGCCCCAGGGG
	CCTCTCCCCGGCTGCCCACTTGGGAGACGGGTCTTCTGACCTCATCCTCATCCGGAAATGCTCCAGGT
	TCAATTTTCTGAGATTTCTCATCAGGCACACCAACCAGCAGGACCAGTTTGACTTCACTTTTGTTGAA
	GTTTATCGCGTCAAGAAATTCCAGTTTACGTCGAAGCACATGGAGGATGAGGACAGCGACCTCAAGGA
	GGGGGGGAAGAAGCGCTTTGGGCACATTTGCAGCAGCCACCCCTCCTGCTGCTGCACCGTCTCCAACA
	GCTCCTGGAACTGCGACGGGGAGGTCCTGCACAGCCCTGCCATCGAGGTCAGAGTCCACTGCCAGCTG
	GTTCGACTCTTTGCACGAGGAATTGAAGAGAATCCGAAGCCAGACTCACACAGCTGAGAAGCCGGCGT
	CCTGCTCTCGAACTGGGAAAGTGTGAAAACTATTTAAGAT
	ORF Start: ATG at 76		ORF Stop: TGA at 1687
	SEQ ID NO: 40	537 aa	MW at 59976.9kD
NOV9a,	MGATGAAEPLQSVLWVKQQRCAVSLEPARALLRWWRSPGPGAGAPGADACSVPVSEIIAVEETDVHGK
CG143216-01
Protein	HQGSGKWQKMEKPYAFTVHCVKRARRHRWKWAQVTFWCPEEQLCHLWLQTLREMLEKLTSRPKHLLVF
Sequence
	INPFGGKGQGKRIYERKVAPLFTLASITTDIIVTEHANQAKETLYEINIDKYDGIVCVGGDGMFSEVL
	HGLIGRTQRSAGVDQNHPRAVLVPSSLRIGIIPAGSTDCVCYSTVGTSDAETSALHIVVGDSLAMDVS
	SVHHNSTLLRYSVSLLGYGFYGDIIKDSEKKRWLGLARYDFSGLKTFLSHHCYEGTVSFLPAQHTVGS
	PRDRKPCRAGCFVCRQSKQQLEEEQKKALYGLEAAEDVEEWQVVCGKFLAINATNMSCACRRSPRGLS
	PAAHLGDGSSDLILIRKCSRFNFLRFLIRHTNQQDQFDFTFVEVYRVKKFQFTSKHMEDEDSDLKEGG
	KKRFGHICSSHPSCCCTVSNSSWNCDGEVLHSPAIEVRVHCQLVRLFARGIEENPKPDSHS

[0394] Further analysis of the NOV9a protein yielded the following properties shown in Table 9B.

TABLE 9B
Protein Sequence Properties NOV9a
PSort     0.5121 probability located in microbody (peroxisome);
analysis: 0.3000 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:

[0395] 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
			Identities/
Geneseq	Protein/Organism/Length	NOV9a Residues/	Similarities for the	Expect
Identifier	[Patent #, Date]	Match Residues	Matched Region	Value
ABB07857	Human sphingosine	1 . . . 537	537/537 (100%)	0.0
	kinase-like protein - Homo	26 . . . 562	537/537 (100%)
	sapiens, 562 aa.
	[WO200228906-A2,
	11 APR. 2002]
ABB07856	Human sphingosine	1 . . . 537	537/537 (100%)	0.0
	kinase-like protein - Homo	1 . . . 537	537/537 (100%)
	sapiens, 537 aa.
	[WO200228906-A2,
	11 APR. 2002]
AAM49115	Human ceramide kinase	1 . . . 537	535/537 (99%)	0.0
	hCERK1 - Homo sapiens,	1 . . . 537	536/537 (99%)
	537 aa. [WO200196575-A1,
	20 DEC. 2001]
AAY96059	Human sphingosine kinase	78 . . . 537	458/460 (99%)	0.0
	C - Homo sapiens, 460 aa.	1 . . . 460	459/460 (99%)
	[WO200052173-A2,
	08 SEP. 2000]
AAE07884	Human sphingosine kinase	78 . . . 537	459/471 (97%)	0.0
	(SphK) protein #2 - Homo	1 . . . 471	460/471 (97%)
	sapiens, 471 aa.
	[WO200160990-A2,
	23 AUG. 2001]

[0396] 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
Protein			Identities/
Accession		NOV9a Residues/	Similarities for the	Expect
Number	Protein/Organism/Length	Match Residues	Matched Portion	Value
Q8TCT0	Putative lipid kinase - Homo	1 . . . 537	537/537 (100%)	0.0
	sapiens (Human), 537 aa.	1 . . . 537	537/537 (100%)
Q9BYB3	KIAA1646 protein - Homo	57 . . . 537	481/481 (100%)	0.0
	sapiens (Human), 481 aa	1 . . . 481	481/481 (100%)
	(fragment).
BAC01155	Ceramide kinases - Mus	1 . . . 529	450/529 (85%)	0.0
	musculus (Mouse), 531 aa.	1 . . . 529	483/529 (91%)
Q9UGE5	DA59H18.2 (Novel protein	130 . . . 444	314/326 (96%)	0.0
	similar to human, mouse,	1 . . . 326	315/326 (96%)
	yeast, worm and plant
	(Predicted) proteins) - Homo
	sapiens (Human), 326 aa
	(fragment).
Q9TZI1	T10B11.2 protein -	79 . . . 525	141/458 (30%)	1e−52
	Caenorhabditis elegans, 549	115 . . . 526	230/458 (49%)
	aa.

[0397] PFam analysis predicts that the NOV9a protein contains the domains shown in the Table 9E.

TABLE 9E
Domain Analysis of NOV9a
		Identities/
	NOV9a	Similarities
	Match	for the	Expect
Pfam Domain	Region	Matched Region	Value
PH	32 . . . 124	9/93 (10%)	0.38
		64/93 (69%)
DAGKc	132 . . . 278	32/165 (19%)	0.00015
		100/165 (61%)

Example 10

[0398] 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:41	772 bp
NOV 10a,	AACTGGAGACCACAACTTCATGCTGCGTGGGATCTCCCAACTACCTGCAGTGGCCACCATGTCTTGG
CG143787-01
DNA Sequence	GTCCTGCTGCCTGTACTTTGGCTCATTGTTCAAACTCAAGCAATAGCCATAAAGCAAACACCTGAAT
	TAACGCTCCATGAAATAGTTTGTCCTAAAAAACTTCACATTTTACACAAAAGAGAGATCAAGAACAA
	CCAGACAGAAAAGCATGGCAAAGAGGAAAGGTATGAACCTGAAGTTCAATATCAGATGATCTTAAAT
	GGAGAAGAAATCATTCTCTCCCTACAAAAAACCAAGCACCTCCTGGGGCCAGACTACACTGAAACAT
	TGTACTCACCCAGAGGAGAGGAAATTACCACGAAACCTGAGAACATGGAACACTGTTACTATAAAGG
	AAACATCCTAAATGAAAAGAATTCTGTTGCCAGCATCAGTACTTGTGACGGGTTGAGAGGATACTTC
	ACACATCATCACCAAAGATACCTTTTATCTCAGAAACCAAAGTGCCTGCTGCAAGCACCTATTCCTA
	CAAATATAATGACAACACCAGTGTGTGGGAACCACCTTCTAGAAGTGGGAGAAGACTGTGATTGTGG
	CTCTCTTAAGGAGTGTACCAATCTCTGCTGTGAAGCCCTAACGTGTAAACTGAAGCCTGGAACTGAT
	TGCGGAGGAGATGCTCCAAACCATACCACAGAGTGAATCCAAAAGTCTGCTTCACTGAGATGCTACC
	TTGCCAGGACAAGAACCAAGAACTCTAACTGTCCC
	ORF Start: ATG at 20		ORF Stop: TGA at 704
	SEQ ID NO: 42	228aa	MW at 25718.4 kD
NOV10a,	MLRGISQLPAVATMSWVLLPVLWLIVQTQAIAIKQTPELTLHEIVCPKKLHILHKREIKNNQTEKHG
CG143787-01
Protein Sequence	KEERYEPEVQYQMILNGEEIILSLQKTKHLLGPDYTETLYSPRGEEITTKPENMEHCYYKGNILNEK
	NSVASISTCDGLRGYFTHHHQRYLLSQKPKCLLQAPIPTNIMTTPVCGNHLLEVGEDCDCGSLKECT
	NLCCEALTCKLKPGTDCGGDAPNHTTE
	SEQ ID NO: 43	706 bp
NOV10b,	CACCGGATCCACCATGCTGCGTGGGATCTCCCAACTACCTGCAGTGGCCACCATGTCTTGGGTCCTG
278889162
DNA Sequence	CTGCCTGTACTTTGGCTCATTGTTCAAACTCAAGCAATAGCCATAAAGCAAACACCTGAATTAACGC
	TCCATGAAATAGTTTGTCCTAAAAAACTTCACATTTTACACAAAAGAGAGATCAAGAACAACCAGAC
	AGAAAAGCATGGCAAAGAGGAAAGGTATGAACCTGAAGTTCAATATCAGATGATCTTAAATGGAGAA
	GAAATCATTCTCTCCCTACAAAAAACCAAGCACCTCCTGGGGCCAGACTACACTGAAACATTGTACT
	CACCCAGAGGAGAGGAAATTACCACGAAACCTGAGAACATGGAACACTGTTACTATAAAGGAAACAT
	CCTAAATGAAAAGAATTCTGTTGCCAGCATCAGTACTTGTGACGGGTTGAGAGGATACTTCACACAT
	CATCACCAAAGATACCTTTTATCTCAGAAACCAAAGTGCCTGCTGCAAGCACCTATTCCTACAAATA
	TAATGACAACACCAGTGTGTGGCAACCACCTTCTAGAAGTGGGAGAAGACTGTGATTGTGGCTCTCT
	TAAGGAGTGTACCAATCTCTGCTGTGAAGCCCTAACGTGTAAACTGAAGCCTGGAACTGATTGCGGA
	GGAGATGCTCCAAACCATACCACAGAGCTCGAGGGC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO:45	118 bp
NOV10c,	TGSTMLRGISQLPAVATMSWVLLPVLWLIVQTQAIAIKQTPELTLHEIVCPKKLHILHKREIKNNQT
278689868
DNA Sequence	EKHGKEERYEPEVQYQMILNGEEIILSLQKTKHLLGPDYTETLYSPRGEEITTKPENMEHCYYKGNI
	LNEKNSVASISTCDGLRGYFTHHHQRYLLSQKPKCLLQAPIPTNIMTTPVCGNHLLEVGEDCDCGSL
	KECTNLCCEALTCKLKPGTDCGGDAPNHTTELEG
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO: 46	39 aa	MW at 3983.4 kD
NOV10c,	CACCGGATCCGAAGTGGGAGAAGACTGTGATTGTGGCTCTCTTAAGGAGTGTACCAATCTCTGCTGT
278689868
DNA Sequence	GAAGCCCTAACGTGTAAACTGAAGCCTGGAACTGATTGCGGACTCGAGGGC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO:46	39 aa	MW at 3983.4 kD
NOV10c,	TGSEVGEDCDCGSLKECTNLCCEALTCKLKPGTDCGLEG
278689868
Protein Sequence

[0399] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 10B.

TABLE 10B
Comparison of NOV10a against NOV10b and NOV10c.
			Identities/
			Similarities
		NOV10a Residues/	for the
	Protein Sequence	Match Residues	Matched Region
	NOV10b	1 . . . 228	228/228 (100%)
		5 . . . 232	228/228 (100%)
	NOV10c	187 . . . 219	33/33 (100%)
		4 . . . 36	33/33 (100%)

[0400] Further analysis of the NOV10a protein yielded the following properties shown in Table 10C.

TABLE 10C
Protein Sequence Properties NOV10a
PSort     0.8200 probability located in outside; 0.1900 probability
analysis: located in lysosome(lumen); 0.1000 probability located
          in endoplasmic reticulum (membrane);0.1000 probability
          located in endoplasmic reticulum (lumen)
SignalP   Cleavage site between residues 33 and 34
analysis:

[0401] A search of the NOV10a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 10D.

TABLE 10D
Geneseq Results for NOV10a
			Identities/
			Similarities
Geneseq	Protein/Organism/Length	NOV10a Residues/	for the	Expect
Identifier	[Patent #, Date]	Match Residues	Matched Region	Value
AAW75769	Human metalloproteinase	1 . . . 157	157/157 (100%)	7e−90
	BS10.55 - Homo sapiens,	1 . . . 157	157/157 (100%)
	470 aa. [WO9839421-A2,
	11 SEP. 1998]
AAW28509	Product of clone J5 - Homo	1 . . . 157	157/157 (100%)	7e−90
	sapiens, 470 aa.	1 . . . 157	157/157 (100%)
	[WO9707198-A2,
	27 FEB. 1997]
AAB53240	Human colon cancer antigen	153 . . . 228	73/76 (96%)	7e−41
	protein sequence SEQ ID	35 . . . 110	74/76 (97%)
	NO: 780 - Homo sapiens, 110
	aa. [WO200055351-A1,
	21 SEP. 2000]
ABB11929	Human eMDC II protein	18 . . . 159	71/142 (50%)	2e−32
	homologue, SEQ ID	18 . . . 153	99/142 (69%)
	NO: 2299 - Homo sapiens,
	788 aa. [WO200157188-A2,
	09 AUG. 2001]
AAW90865	Human ADAM protein #4 -	18 . . . 159	71/142 (50%)	2e−32
	Homo sapiens, 775 aa.	5 . . . 140	99/142 (69%)
	[WO200014227-A1,
	16 MAR. 2000]

[0402] In a BLAST search of public sequence datbases, the NOV10a protein was found to have homology to the proteins shown in the BLASTP data in Table 10E.

TABLE 10E
Public BLASTP Results for NOV10a
			Identities/
Protein			Similarities
Accession		NOV10a Residues/	for the	Expect
Number	Protein/Organism/Length	Match Residues	Matched Portion	Value
O15204	Disintegrin-protease - Homo	1 . . . 157	157/157 (100%)	2e−89
	sapiens (Human), 470 aa.	1 . . . 157	157/157 (100%)
Q9R0X2	Disintegrin metalloprotease	1 . . . 157	104/157 (66%)	8e−56
	precursor - Mus musculus	1 . . . 157	124/157 (78%)
	(Mouse), 467 aa.
Q9XSL6	ADAM 28 precursor (EC	14 . . . 159	70/146 (47%)	1e−32
	3.4.24.-) (A disintegrin and	1 . . . 141	101/146 (68%)
	metalloproteinase domain 28)
	(eMDC II) - Macaca
	fascicularis (Crab eating
	macaque) (Cynomolgus
	monkey), 776 aa.
E1262181	SEQUENCE 3 FROM	18 . . . 159	71/142 (50%)	5e−32
	PATENT WO9709430 -	5 . . . 140	99/142 (69%)
	unidentified, 530 aa.
Q9UKQ2	ADAM 28 precursor (EC	18 . . . 159	71/142 (50%)	5e−32
	3.4.24.-) (A disintegrin and	5 . . . 140	99/142 (69%)
	metalloproteinase domain 28)
	(Metalloproteinase-like,
	disintegrin-like, and cysteine-
	rich protein-L) (MDC-L)
	(eMDC II) (ADAM23) -
	Homo sapiens (Human), 775
	aa.

[0403] PFam analysis predicts that the NOV10 a protein contains the domains shown in the Table 10F.

TABLE 10F
Domain Analysis of NOV10a
		Identities/
		Similarities
Pfam	NOV10a Match	for the Matched	Expect
Domain	Region	Region	Value
Pep_M12B_propep	90 . . . 201	32/119 (27%)	1.8e−20
		79/119 (66%)
disintegrin	187 . . . 219	20/33 (61%)	4e−14
		26/33 (79%)

Example 11

[0404] 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: 47	484 bp
NOV11a,	ACTGGGTCCGAATCAGTAGGTGACCCCGCCCCTGGATTCTGGAAGACCTCACCATGGGACGCCCCCG
CG144112-01
DNA Sequence	ACCTCGTGCGGCCAAGACGTGGATGTTCCTGCTCTTGCTGGGGGGAGCCTGGGCAGGAAATACACAG
	TACGCCTGGGAGACCACAGCCTACAGAATAAAGATGGCCCAGAAGTGCAGTCCCCGAGAGAATTTTC
	CTGACACTCTCAACTGTGCAGAAGTAAAAATCTTTCCCCAGAAGAAGTGTGAGGATGCTTACCCGGG
	GCAGATCACAGATGGCATGGTCTGTGCAGGCAGCAGCAAAGGGGCTGACACGTGCCAGGGCGATTCT
	GGAGGCCCCCTGGTGTGTGATGGTGCACTCCAGGGCATCACATCCTGGGGCTCAGACCCCTGTGGGA
	GGTCCGACAAACCTGGCGTCTATACCAACATCTGCCGCTACCTGGACTGGATCAAGAAGATCATAGG
	CAGCAAGGGCTGATT
	ORF Start: ATG at 54		ORF Stop: TGA at 480
	SEQ ID NO: 48	142 aa	MW at 15404.5 kD
NOV11a,	MGRPRPRAAKTWMFLLLLGGAWAGNTQYAWETTAYRIKMAQKCSPRENFPDTLNCAEVKIFPQKKCE
CG144112-01
Protein Sequence	DAYPGQITDGMVCAGSSKGADTCQGDSGGPLVCDGALQGITSWGSDPCGRSDKPGVYTNICRYLDWI
	KKIIGSKG
	SEQ ID NO: 49	288 bp
NOV11b,	CCCCGCCCCTGGATTCTGGAAGACCTCACCATGGGACGCCCCCGACCTCGTGCGGCCAAGACGTGGA
CG144112-04
DNA Sequence	TGTTCCTGCTCTTGCTGGGGGGAGCCTGGGCAGGGCAGGGCGATTCTGGAGGCCCCCTGGTGTGTGA
	TGGTGCACTCCAGGGCATCACATCCTGGGGCTCAGACCCCTGTGGGAGGTCCGACAAACCTGGCGTC
	TATACCAACATCTGCCGCTACCTGGACTGGATCAAGAAGATCATAGGCAGCAAGGGCTGATTCTAGG
	ATAAGCACTAGATCTCCCTT
	ORF Start: ATG at 31		ORF Stop: TGA at 259
	SEQ ID NO: 50	76 aa	MW at 8110.3 kD
NOV11b,	MGRPRPRAAKTWMFLLLLGGAWAGQGDSGGPLVCDGALQGITSWGSDPCGRSDKPGVYTNICRYLDW
CG144112-04
Protein Sequence	IKKIIGSKG
	SEQ ID NO: 51	445 bp
NOV11c,	CACCAAGCTTATGGGACGCCCCCGACCTCGTGCGGCCAAGACGTGGATGTTCCTGCTCTTGCTGGGG
255501898
DNA Sequence	GGAGCCTGGGCAGGAAATACACAGTACGCCTGGGAGACCACAGCCTACAGAATAAAGATGGCCCAGA
	AGTGCAGTCCCCGAGAGAATTTTCCTGACACTCTCAACTGTGCAGAAGTAAAAATCTTTCCCCAGAA
	GAAGTGTGAGGATGCTTACCCGGGGCAGATCACAGATGGCATGGTCTGTGCAGGCAGCAGCAAAGGG
	GCTGACACGTGCCAGGGCGATTCTGGAGGCCCCCTGGTGTGTGATGGTGCACTCCAGGGCATCACAT
	CCTGGGGCTCAGACCCCTGTGGGAGGTCCGACAAACCTGGCGTCTATACCAACATCTGCCGCTACCT
	GGACTGGATCAAGAAGATCATAGGACAGCAAGGGCCTCGAGGGC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO:52	148 aa	MW at 16046.2 kD
NOV11c	TKLMGRPRPRAAKTWMFLLLLGGAWAGNTQYAWETTAYRIKMAQKCSPRENFPDTLNCAEVKIFPQK
255501898
Protein Sequence	KCEDAYPGQITDGMVCAGSSKGADTCQGDSGGPLVCDGALQGITSWGSDPCGRSDKPGVYTNICRYL
	DWIKKIGSKGLEG
	SEQ ID NO:53	358 bp
NOV11d,	CACCAAGCTTGGAAATACACAGTACGCCTGGGAGACCACAGCCTACAGAATAAAGATGGCCCAGAAG
255612524
DNA Sequence	TGCAGTCCCCGAGAGAATTTTCCTGACACTCTCAACTGTGCAGAAGTAAAAATCTTTCCCCAGAAGA
	AGTGTGAGGATGCTTACCCGGGGCAGATCACAGATGGCATGGTCTGTGCAGGCAGCAGCAAAGGGGC
	TGACACGTGCCAGGGCGATTCTGGAGGCCCCCTGGTGTGTGATGGTGCACTCCAGGGCATCACATCC
	TGGGGCTCAGACCCCTGTGGGAGGTCCGACAAACCTGGCGTCTATACCAACATCTGCCGCTACCTGG
	ACTGGATCAAGAAGCTCGAGGGC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO: 54	119 aa	MW at 12908.4 kD
NOV11d,	TKLGNTQYAWETTAYRIKMAQKCSPRENFPDTLNCAEVKIFPQKKCEDAYPGQITDGMVCAGSSKGA
255612524
Protein Sequence	DTCQGDSGGPLVCDGALQGITSWGSDPCGRSDKPGVYTNICRYLDWIKKLEG
	SEQ ID NO: 55	307 bp
NOV11e,	CACCAAGCTTCAGAAGTGCAGTCCCCGAGAGAATTTTCCTGACACTCTCAACTGTGCAGAAGTAAAA
255612566
DNA Sequence	ATCTTTCCCCAGAAGAAGTGTGAGGATGCTTACCCGGGGCAGATCACAGATGGCATGGTCTGTGCAG
	GCAGCAGCAAAGGGGCTGACACGTGCCAGGGCGATTCTGGAGGCCCCCTGGTGTGTGATGGTGCACT
	CCAGGGCATCACATCCTGGGGCTCAGACCCCTGTGGGAGGTCCGACAAACCTGGCGTCTATACCAAC
	ATCTGCCGCTACCTGGACTGGATCAAGAAGCTCGAGGGC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO: 56	102 aa	MW at 10922.2 kD
NOV11e,	TKLQKCSPRENFPDTLNCAEVKIFPQKKCEDAYPGQITDGMVCATSSKGADTCQGDSGGPLVCDGAL
256612566
Protein Sequence	QGITSWGSDPCGRSDKPGVYTNICRYLDWIKKLEG
	SEQ ID NO: 57	178 bp
NOV11f,	CACCGGATCCGGGCAGGGCGATTCTGGAGGCCCCCTGGTGTGTGATGGTGCACTCCAGGGCATCACA
306434072
DNA Sequence	TCCTGGGGCTCAGACCCCTGTGGGAGGTCCGACAAACCTGGCGTCTATACCAACATCTGCCGCTACC
	TGGACTGGATCAAGAAGATCATAGGCAGCAAGGGCCTCGAGGGC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO: 58	59 aa	MW at 6072.7 kD
NOV11f,	TGSGQGDSGGPLVCDGALQGITSWGSDPCGRSDKPGVYTNICRYLDWIKKIIGSKGLEG
306434072
Protein Sequence
	SEQ ID NO: 59	436 bp
NOV11g,	AGTGTGCTGGAATTCGCCCTTACTGGGTCCGAATCAGTAGGTGACCCCGCCCCTGGATTCTTGAAGA
CG144112-02
DNA Sequence	CCTCACCATGGGACGCCCCCGACCTCGTGCGGCCAAGACGTGGATGTTCCTGCTCTTGCTGGGGGGA
	GCCTGGGCAGAGAATTTTCCTGACACTCTCAACTGTGCAGAAGTAAAAATCTTTCCCCAGAAGAAGT
	GTGAGGATGCTTACCCGGGGCAGATCACAGATGGCATGGTCTGTGCAGGCAGCAGCAAAGGGGCTGA
	CACGTGCCAGGGCGATTCTGGAGGCCCCCTGGTGTGTGATGGTGCACTCCAGGGCATCACATCCTGG
	GGCTCAGACCCCTGTGGGAGGTCCGACAAACCTGGCGTCTATACCAACATCTGCCGCTACCTGGACT
	GGATCAAGAAGATCATAGGCAGCAAGGGCTGATT
	ORF Start: ATG at 75		ORF Stop: TGA at 432
	SEQ ID NO: 60	119 aa	MW at 12718.4kD
NOV11g,	MGRPRPRAAKTWMFLLLLGGAWAENFPDTLNCAEVKIFPQKKCEDAYPGQITDGMVCAGSSKGADTC
CG144112-02
Protein Sequence	QCDSGGPLVCDGALQGITSWGSDPCGRSDKPGVYTNICRYLDWIKKIIGSKG
	SEQ ID NO: 61	845 bp
NOV11h,	CGCCCTTACTGGGTCCGAATCAGTAGGTGACCCCGCCCCTGGATTCTGGAAGACCTCACCATGGGAC
CG144112-03
DNA Sequence	GCCCCCGACCTCGTGCGGCCAAGACGTGGATGTTCCTGCTCTTGCTGGGGGGAGCCTGGGCAGGACA
	CTCCAGGGCACAGGAGGACAAGGTGCTGGGGGGTCATGAGTGCCAACCCCATTCGCAGCCTTGGCAG
	GCGGCCTTGTTCCAGGGCCAGCAACTACTCTGTGGCGGTGTCCTTGTAGGTGGCAACTGGGTCCTTA
	CAGCTGCCCACTGTAAAAAACCGAAATACACAGTACGCCTGGGAGACCACAGCCTACAGAATAAAGA
	TGGCCCAGAGCAAGAAATACCTGTGGTTCAGTCCATCCCACACCCCTGCTACAACAGCAGCGATGTG
	GAGGACCACAACCATGATCTGATGCTTCTTCAACTGCGTGACCAGGCATCCCTGGGGTCCAAAGTGA
	AGCCCATCAGCCTGGCAGATCATTGCACCCAGCCTGGCCAGAAGTGCACCGTCTCAGGCTGGGGCAC
	TGTCACCAGTCCCCGAGAGAATTTTCCTGACACTCTCAACTGTGCAGAAGTAAAAATCTTTCCCCAG
	AAGAAGTGTGAGGATGCTTACCCGGGGCAGATCACAGATGGCATGGTCTGTGCAGGCAGCAGCAAAG
	GGGCTGACACGTGCCAGGGCGATTCTGGAGGCCCCCTGGTGTGTGATGGTGCACTCCAGGGCATCAC
	ATCCTGGGGCTCAGACCCCTGTGGGAGGTCCGACAAACCTGGCGTCTATACCAACATCTGCCGCTAC
	CTGGACTGGATCAAGAAGATCATAGGCAGCAAGGGCTGATT
	ORF Start: ATG at 61		ORF Stop: TGA at 841
	SEQ ID NO: 62	260 aa	MW at 28047.6 kD
NOV11h,	MGRPRPRAAKTWMFLLLLGGAWAGHSRAQEDKVLGGHECQPHSQPWQAALFQGQQLLCGGVLVGGNW
CG114112-03
Protein Sequence	VLTAAHCKKPKYTVRLGDHSLQNKDGPEQEIPVVQSIPHPCYNSSDVEDHNHDLMLLQLRDQASLGS
	KVKPISLADHCTQPGQKCTVSGWGTVTSPRENFPDTLNCAEVKIFPQKKCEDAYPGQITDGMVCAGS
	SKGADTCQGDSGGPLVCDGALQGITSWGSDPCGRSDKPGVYTNICRYLDWIKKIIGSKG

[0405] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 11B.

TABLE 11B
Comparison of NOV11a against NOV11b through NOV11h.
			Identities/
		NOV11a Residues/	Similarities for
	Protein Sequence	Match Residues	the Matched Region
	NOV11b	97 . . . 142	46/46 (100%)
		31 . . . 76	46/46 (100%)
	NOV11c	1 . . . 142	142/142 (100%)
		4 . . . 145	142/142 (100%)
	NOV11d	24 . . . 139	114/116 (98%)
		4 . . . 119	115/116 (98%)
	NOV11e	41 . . . 139	97/99 (97%)
		4 . . . 102	98/99 (98%)
	NOV11f	91 . . . 142	52/52 (100%)
		5 . . . 56	52/52 (100%)
	NOV11g	1 . . . 142	119/142 (83%)
		1 . . . 119	119/142 (83%)
	NOV11h	44 . . . 142	99/99 (100%)
		162 . . . 260	99/99 (100%)

[0406] Further analysis of the NOV11 a protein yielded the following properties shown in Table 11C.

TABLE 11C
Protein Sequence Properties NOV11a
PSort analysis:   0.3700 probability located in outside; 0.1000
                  probability located in endoplasmic reticulum
                  (membrane); 0.1000 probability located in
                  endoplasmic reticulum (lumen); 0.1000
                  probability located in lysosome (lumen)
SignaIP analysis: Cleavage site between residues 24 and 25

[0407] A search of the NOV11a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 11D.

TABLE 11D
Geneseq Results for NOV11a
		NOV11a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
ABP41332	Human ovarian antigen	44 . . . 142	99/99 (100%)	3e−57
	HCOQP78, SEQ ID NO: 2464 -	217 . . . 315	99/99 (100%)
	Homo sapiens, 315 aa.
	[WO200200677-A1,
	03-JAN-2002]
AAU81959	Human PR0322 - Homo	44 . . . 142	99/99 (100%)	3e−57
	sapiens, 260 aa.	162 . . . 260	99/99 (100%)
	[WO200109327-A2,
	08-FEB-2001]
ABB84852	Human PR0322 protein	44 . . . 142	99/99 (100%)	3e−57
	sequence SEQ ID NO: 72 -	162 . . . 260	99/99 (100%)
	Homo sapiens, 260 aa.
	[WO200200690-A2,
	03-JAN-2002]
ABB95458	Human angiogenesis related	44 . . . 142	99/99 (100%)	3e−57
	protein PR0322 SEQ ID NO:	162 . . . 260	99/99 (100%)
	72 - Homo sapiens, 260 aa.
	[WO200208284-A2,
	31-JAN-2002]
AAB53087	Human	44 . . . 142	99/99 (100%)	3e−57
	angiogenesis-associated	162 . . . 260	99/99 (100%)
	protein PR0322, SEQ ID
	NO: 127 - Homo sapiens, 260
	aa. [WO200053753-A2,
	14-SEP-2000]

[0408] 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 11E.

TABLE 11E
Public BLASTP Results for NOV11a
		NOV11a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9NR68	Serine protease	1 . . . 142	119/142 (83%)	9e−66
	kallikrein/ovasin/neuropsin	1 . . . 119	119/142 (83%)
	Type 3 - Homo sapiens
	(Human), 119 aa.
060259	Neuropsin precursor (EC	44 . . . 142	99/99 (100%)	9e−57
	3.4.21.-) (NP) (Kallikrein 8)	162 . . . 260	99/99 (100%)
	(Ovasin) (Serine protease
	TADG-14)
	(Tumor-associated
	differentially expressed
	gene-14 protein) - Homo
	sapiens (Human), 260 aa.
088780	Neuropsin precursor (EC	38 . . . 141	80/113 (70%)	8e−45
	3.4.21.-) (NP) (Kallikrein 8)	147 . . . 259	93/113 (81%)
	(Brain serine protease 1) -
	Rattus norvegicus (Rat), 260
	aa.
BAB92021	Neuropsin-Musmusculus	38 . . . 141	81/113 (71%)	le−44
	(Mouse), 176 aa (fragment).	63 . . . 175	92/113 (80%)
Q61955	Neuropsin precursor (EC	38 . . . 141	81/113 (71%)	le−44
	3.4.21.-) (NP) (Kallikrein 8)-	147 . . . 259	92/113 (80%)
	Mus musculus (Mouse), 260
	aa.

[0409] PFam analysis predicts that the NOV11a protein contains the domains shown in the Table 11F.

TABLE 11F
Domain Analysis of NOV11a
			Identities/
	Pfam	NOV11a	Similarities	Expect
	Domain	Match Region	for the Matched Region	Value
	trypsin	49 . . . 134	47/101 (47%)	5.5e−40
			76/101 (75%)

Example 12

[0410] 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:63	1536 bp
NOV12a,	AAGAGCCAAGCCAGCATGTCGGGGACCCGAGCCTCCAACGACCGGCCCCCCGGCGCAGGCGGCGTCA
CG14497-01
DNA Sequence	AGCGGGGGCGGCTGCAGCAGGAGGCGGCGGCGACCGGCTCCCGCGTGACGGTGGTGCTGGGCGCGCA
	GTGGGGGGACGAGGGCAAAGGCAAGGTGGTGGACCTGCTGGCCACGGACGCCGACATCATCAGCCGC
	TGCCAGGGGGGCAACAACGCCGGCCACACGGTGGTGGTGGATGGGAAAGAGTACGACTTCCACCTGC
	TGCCCAGCGGCATCATCAACACCAAGGCCGTGTCCTTCATTGGTAACGGGGTGGTCATCCACTTGCC
	AGGCTTGTTTGAGGAAGCAGAGAAGAATGAAAAGAAACGTCTGAAGGACTGGGAGAAGAGGCTCATC
	ATCTCTGACAGAGCCCACCTTGTGTTTGATTTTCACCAGGCTGTCGACGGACTTCAGGAAGTGCAGC
	GCCAGGCACAAGAGGGGAAGAGTATAGGCACCACCAAGAAGGGAATCGGACCAACCTACTCTTCCAA
	AGCTGCCCGGACAGGCCTCCGCATCTGCGACCTCCTGTCAGATTTTGATGAGTTTTCCTCCAGATTC
	AAGAACCTGGCCCACCAGCACCAGTCGATGTTCCCCACCCTGGAAATAGACATTGAAGGCCAACTCA
	AAAGGCTCAAGGGCTTTGCTGAGCGGATCAGACCCATGGTCCGAGATGGTGTTTACTTTATGTATGA
	GGCACTCCACGGCCCCCCCAAGAAGATCCTGGTGGAGGGTGCCAACGCCGCCCTCCTCGACATTGAC
	TTCGGTACCTACCCCTTTGTGACTTCATCCAACTGCACCGTGGGCGGTGTGTGCACGGGCCTGGGCA
	TCCCCCCGCAGAACATAGGTGACGTGTATGGCGTGGTGAAAGCCTATACCACACGTGTGGGCATCGG
	GGCCTTCCCCACCGAGCAGATCAACGAGATTGGAGGCCTGCTGCAGACCCGCGGCCACGAGTGGGGA
	GTGACCACAGGCAGGAAGAGGCGCTGCGGCTGGCTCGACCTGATGATTCTAAGATATGCTCACATGG
	TCAACGGATTCACTGCGCTGGCCCTGACGAAGCTGGACATCCTGGACGTACTGGGTGAGGTTAAAGT
	CGGTGTCTCATACAAGCTGAACGGGAAAAGGATTCCCTATTTCCCAGCTAACCAGGAGATGCTTCAG
	AAGGTCGAAGTTGAGTATGAAACGCTGCCTGGGTGGAAAGCAGACACCACAGGCGCCAGGAGGTGGG
	AGGACCTGCCCCCACAGGCCCAGAACTACATCCGCTTTGTGGAGAATCACGTGGGAGTCGCAGTCAA
	ATGGGTTGGTGTTGGCAAGTCAAGAGAGTCGATGATCCAGCTGTTTTAGTCACAGACTGAGCTGATC
	CCAACAGGCCCTGGCAGCGTCTGGACTTGTGTAAACAGCAGCAGTCACGTTCCTCGGCCGCCACAAC
	CAACACCAAAGCAGGAAAACCATTTTCTGTACTTTTATATTTCTGTTCAACCTGTTGGTTTC
	ORF Start: ATG at 16		ORF Stop: TAG at 1387
	SEQ ID NO: 64	457aa	MW at 50181.0 kD
NOV12a,	MSGTRASNDRPPGAGGVKRGRLQQEAAATGSRVTVVLGAQWGDEGKGKVVDLLATDATIISRCQGGN
CG144497-01
Protein Sequence	NAGHTVVVDGKEYDFHLLPSGIINTKAVSFIGNGVVIHLPGLFEEAEKNEKKGLKDWEKRLIISDRA
	HLVFDFHQAVDGLQEVQRQAQEGKSIGTTKKGIGPTYSSKAARTGLRICDLLSDFDEFSSRFKNLAH
	QHQSMFPTLEIDIEGQLKRLKGFAERIRPMVRDGVYFMYEALHGPPKKILVEGANAALLDIDFGTYP
	FVTSSNCTVGGVCTGLGIPPQNIGDVYGVVKAYTTRVGIGAFPTEQINEIGGLLQTRGHEWGVTTGR
	KRRCGWLDLMILRYAHMVNGFTALALTKLDILDVLGEVKVGVSYKLNGKRIPYFPANQEMLQKVEVE
	YETLPGWKADTTGARRWEDLPPQAQNYIRFVENHVGVAVKWVGVGKSRESMIQLF

[0411] Further analysis of the NOV12a protein yielded the following properties shown in Table 12B.

TABLE 12B
Protein Sequence Properties NOV12a
PSort analysis:   0.5946 probability located in microbody
                  (peroxisome); 0.3000 probability located in nucleus;
                  0.2377 probability located in lysosome (lumen);
                  0.1000 probability located in mitochondrial
                  matrix space
SignalP analysis: No Known Signal Sequence Predicted

[0412] A search of the NOV 12a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 12C.

TABLE 12C
Geneseq Results for NOV12a
		NOV12a
		Residues/	Identities/Similarities
Geneseq	Protein/Organism/Length	Match	for the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAB41627	Human ORFX ORF1391	144 . . . 457	313/314 (99%)	0.0
	polypeptide sequence SEQ ID NO:	1 . . . 314	314/314 (99%)
	2782 - Homo sapiens,
	314 aa. [WO200058473-A2,
	05-OCT-2000]
ABB70971	Drosophila melanogaster	31 . . . 456	270/427 (63%)	e−161
	polypeptide SEQ ID NO	24 . . . 446	338/427 (78%)
	39705 - Drosophila
	melanogaster, 447 aa.
	[WO200171042-A2,
	27-SEP-2001]
AAY95049	Candida albicans polypeptide	35 . . . 455	227/425 (53%)	e−130
	sequence #17 - Candida	4 . . . 409	306/425 (71%)
	albicans, 412 aa.
	[EP982401-A2,
	01-MAR-2000]
AAU23499	Novel human enzyme	249 . . . 457	208/209 (99%)	e−121
	polypeptide #585 - Homo	1 . . . 209	209/209 (99%)
	sapiens, 209 aa.
	[WO200155301-A2,
	02-AUG-2001]
AAW99455	Maize adenylosuccinate	24 . . . 454	217/436 (49%)	e−119
	synthetase - Zea mays, 484	53 . . . 482	310/436 (70%)
	aa. [US5882869-A,
	16-MAR-1999]

[0413] In a BLAST search of public sequence datbases, the NOV12a protein was found to have homology to the proteins shown in the BLASTP data in Table 12D.

Table 12D
Public BLASTP Results for NOV12a
		NOV12a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
BAC04649	CDNA FLJ38602 fis, clone	1 . . . 457	456/457 (99%)	0.0
	HEART2003836, highly	1 . . . 457	457/457 (99%)
	similar to
	ADENYLOSUCCINATE
	SYNTHETASE, MUSCLE
	ISOZYME (EC 6.3.4.4) -
	Homo sapiens (Human), 457
	aa.
P28650	Adenylosuccinate synthetase,	1 . . . 457	441/457 (96%)	0.0
	muscle isozyme (EC 6.3.4.4)	1 . . . 457	453/457 (98%)
	(IMP-- aspartate ligase)
	(ADSS) (AMPSASE) - Mus
	musculus (Mouse), 457 aa.
AJMSDS	adenylosuccinate synthase	1 . . . 425	411/425 (96%)	0.0
	(EC 6.3.4.4), muscle - mouse,	1 . . . 425	421/425 (98%)
	452 aa.
AAH32039	Similar to	64 . . . 457	392/394 (99%)	0.0
	ADENYLOSUCCINATE	109 . . . 502	394/394 (99%)
	SYNTHETASE, MUSCLE
	ISOZYME
	(IMP--ASPARTATE
	LIGASE) (ADSS)
	(AMIPSASE) - Homo sapiens
	(Human), 502 aa (fragment).
Q9CQL9	Adenylosuccinate synthetase	8 . . . 457	345/453 (76%)	0.0
	(EC 6.3.4.4) (IMP--aspartate	4 . . . 456	399/453 (87%)
	ligase) (ADSS) (AMPSase) -
	Mus musculus (Mouse), 456
	aa.

[0414] PFam analysis predicts that the NOV12a protein contains the domains shown in the Table 12E.

TABLE 12E
Domain Analysis of NOV12a
		Identities/
Pfam	NOV12a Match	Similarities	Expect
Domain	Region	for the Matched Region	Value
Ald_Xan_dh_C	396 . . . 411	8/16 (50%)	0.43
		14/16 (88%)
Adenylsucc_synt	32 . . . 455	261/431 (61%)	0
		417/431 (97%)

Example 13

[0415] 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:65	278 bp
NOV13a,	TGCCTGTGGGTTTGATTGCTACCACTCTTGCAATTGCTCCTGTCCGCTTTGACAGGGAGAAGGTGTT
CG144686-01
DNA Sequence	CCGCGTGAAGCCTCAGGATGAAAAACAAGCAGACATCATAAAGGACTTGGCCAAAACCAGTGAGCTC
	CGAGATAAAGGCAAATTTGGTTTTCTCCTTCCAGAATCCCGGATAAAGCCAACGTGCAGAGAGACCA
	TGCTAGCTGTCAAATTTATTGCCAAGTATATCCTCAAGCATACTTCCTAAAGAACTGCCCTCTGTTT
	GGAATAAGCC
	ORF Start: at 3		ORF Stop: TAA at 249
	SEQ ID NO: 66	82 aa	MW at 9327.9kD
NOV13a,	PVGLIATTLAIAPVRFDREKVFRVKPQDEKQADIIKDLAKTSELRDKGKFGFLLPESRIKPTCRETM
CG144686-01
Protein Sequence	LAVKFIAKYILKHTS
	SEQ ID NO: 67	268 bp
NOV13b,	CACCGGATCCACCCCTGTGGGTTTGATTGCTACCACTCTTGCAATTGCTCCTGTCCGCTTTGACAGG
27869008
DNA Sequence	GAGAAGGTGTTCCGCGTGAAGCCTCAGGATGAAAAACAAGCAGACATCATAAAGGACTTGGCCAAAA
	CCAGTGAGCTCCGAGATAAAGGCAAATTTGTTTTCTCCTTCCAGAATCCCGGATAAAGCCAACGTG
	CAGAGAGACCATGCTAGCTGTCAAATTTATTGCCAAGTATATCCTCAAGCATACTTCCCTCGAGGGC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO: 68	89 aa	MW at 9973.6kD
NOV13b,	TGSTPVGLIATTLAIAPVRFDREKVFRVKPQDEKQADIIKDLAKTSELRDKGKFGFLLPESRIKPTC
278690008
Protein Sequence	RETMLAVKFIAKYILKHTSLEG
	SEQ ID NO: 69	94 bp
NOV13c,	CACCGGATCCACCAGTGAGCTCCGAGATAAAGGCAAATTTGGTTTTCTCCTTCCAGAATCCCGGATA
278690035
DNA Sequence	AAGCCAACGTGAGAGAGCTCGAGGGC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO: 70	431 aa	MW at 3452.9kD
NOV13c,	TGSTSELRDKGKFGFLLPESRIKPTCRELEG
278690035
Protein Sequence
	SEQ ID NO:71	1622 bp
NOV13d,	ATGAGGCTCATCCTGCCTGTGGGTTTGATTGCTACCACTCTTGCAATTGCTCCTGTCCGCTTTGACA
CG144686-02
DNA Sequence	GGGAGAAGGTGTTCCGCGTGAAGCCCCAGGATGAAAAACAAGCAGACATCATAAAGGACTTGGCCAA
	AACCAATGAGCTTGACTTCTGGTATCCAGGTGCCACCCACCACGTAGCTGCTAATATGATGGTGGAT
	TTCCGAGTTAGTGAGAAGGAATCCCAAGCCATCCAGTCTGCCTTGGATCAAAATAAAATGCACTATG
	AAATCTTGATTCATGATCTACAAGAAGAGATTGAGAAACAGTTTGATGTTAAAGAAGATATCCCAGG
	CAGGCACAGCTACGCAAAATACAATAATTGGGAAAAGATTGTGGCTTGGACTGAAAAGATGATGGAT
	AAGTATCCTGAAATGGTCTCTCGTATTAAAATTGGATCTACTGTTGAAGATAATCCACTATATGTTC
	TGAAGATTGGGGAAAAGAATGAAAGAAGAAAGGCTATTTTTATGGATTGTGGCATTCACGCACGAGA
	ATGGGTCTCCCCAGCATTCTGCCAGTGGTTTGTCTATCAGGCAACCAAAACTTATGGGAGAAACAAA
	ATTATGACCAAACTCTTGGACCGAATGAATTTTTACATTCTTCCTGTGTTCAATGTTGATGGATATA
	CGGCACTGACCTCAACAGGAATTTTAATGCTTCATGGAACTCCATTCCTAACACCAATGACCCATGT
	GCAGATAACTATCGGGGCTCTGCACCAGAGTCCGAGAAAGAGACGAAAGCTGTCACTAATTTCATTA
	GAAGCCACCTGAATGAAATCAAGGTTTACATCACCTTCCATTCCTACTCCCAGATGCTATTGTTTCC
	CTATGGATATACATCAAAACTGCCACCTAACCATGAGGACTTGGCCAAAGTTGCAAAGATTGGCACT
	GATGTTCTATCAACTCGATATGAAACCCGCTACATCTATGGCCCAATAGAATCAACAATTTACCCGA
	TATCAGGTTCTTCTTTAGACTGGGCTTATGACCTGGGCATCAAACACACATTTGCCTTTGAGCTCCG
	AGATAAAGGCAAATTTGGTTTTCTCCTTCCAGAATCCCGGATAAAGCCAACGTGCAGAGAGACCATG
	CTAGCTGTCAAATTTATTGCCAAGTATATCCTCAAGCATACTTCCTAAAGAACTGCCCTCTGTTTGG
	AATAAGCCAATTAATCCTTTTTTGTGCCTTTCATCAGAAAGTCAATCTTCAGTTATCCCCAAATGCA
	GCTTCTATTTCACCTGAATCCTTCTCTTGCTCATTTAAGTCCCATGTTACTGCTGTTTGCTTTTACT
	TACTTTCAGTAGCACCATAACGAAGTAGCTTTAAGTGAAACCTTTTAACTACCTTTCTTTGCTCCAA
	GTGAAGTTTGGACCCAGCAGAAAGCATTATTTTGAAAGGTGATATACAGTGGGGCACAGAAAACAAA
	TGAAAACCCTCAGTTTCTCACAGATTTTCACCATGTGGCTTCATCAATTTATGTGCTAATACAATAA
	AATAAAATGCACTT
	ORF Start: ATG at 1		ORF Stop: TAA at 1252
	SEQ ID NO: 72	417 aa	MW at 48699.4kD
NOV13d,	MRLILPVGLIATTLAIAPVRFDREKVFRVKPQDEKQADIIKDLAKTNELDFWYPGATHHVAANMMVD
CG144686-02
Protein Sequence	FRVSEKESQAIQSALDQNKMHYEILIHDLQEEIEKQFDVKEDIPGRHSYAKYNNWEKIVAWTEKMMD
	KYPEMVSRIKIGSTVEDNPLYVLKIGEKNERRKAIFMDCGIHAREWVSPAFCQWFVYQATKTYGRNK
	IMTKLLDRMNFYILPVFNVDGYIWSWTKNRMWRKNRSKNQNSKCIGTDLNRNFNASWNSIPNTNDPC
	ADNYRGSAPESEKETKAVTNFIRSHLNEIKVYITFHSYSQMLLFPYGYTSKLPPNHEDLAKVAKIGT
	DVLSTRYETRYIYGPIESTIYPISGSSLDWAYDLGIKHTFAFELRDKGKFGFLLPESRIKPTCRETM
	LAVKFIAKYILKHTS

[0416] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 13B.

TABLE 13B
Comparison of NOV13a against NOV13b through NOV13d.
	Protein	NOV13a Residues/	Identities/Similarities
	Sequence	Match Residues	for the Matched Region
	NOV13b	1 . . . 82	82/82 (100%)
		5 . . . 86	82/82 (100%)
	NOV13c	41 . . . 65	25/25 (100%)
		4 . . . 28	25/25 (100%)
	NOV13d	1 . . . 44	43/44 (97%)
		6 . . . 49	44/44 (99%)

[0417] Further analysis of the NOV13a protein yielded the following properties shown in Table 13C.

TABLE 13C
Protein Sequence Properties NOV13a
PSort analysis:   0.5500 probability located in endoplasmic reticulum
                  (membrane); 0.1900 probability located in lysosome
                  (lumen); 0.1000 probability located in endoplasmic
                  reticulum (lumen); 0.1000 probability located in
                  outside
SignalP analysis: No Known Signal Sequence Predicted

[0418] A search of the NOV13a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 13D.

TABLE 13D
Geneseq Results for NOV13a
			Identities/
			Similarities for
Geneseq	Protein/Organism/Length	NOV13a Residues/	the Matched	Expect
Identifier	[Patent #, Date]	Match Residues	Region	Value
AAU84325	Protein CPA3 differentially	1 . . . 44	43/44 (97%)	2e−17
	expressed in breast cancer	6 . . . 49	44/44 (99%)
	tissue - Homo sapiens, 417
	aa. [WO200210436-A2,
	07-FEB-2002]
AAG75369	Human colon cancer antigen	43 . . . 82	40/40 (100%)	9e−17
	protein SEQ ID NO: 6133 -	141 . . . 180	40/40 (100%)
	Homo sapiens, 180 aa.
	[WO200122920-A2,
	05-APR-200]
AAU04477	Porcine carboxypeptidase B	41 . . . 80	25/40 (62%)	4e−10
	(CpB) protein - Sus scrofa,	266 . . . 305	34/40 (84%)
	306 aa. [WO200151624-A2,
	19-JUL-2001]
AAR75132	Porcine carboxypeptidase B -	41 . . . 80	25/40 (62%)	4e−10
	Sus scrofa, 306 aa.	266 . . . 305	34/40 (84%)
	[WO9514096-A1,
	26-MAY-1995]
AAR75131	Porcine Tyr-His-Met	41 . . . 80	25/40 (62%)	4e−10
	Procarboxypeptidase B - Sus	364 . . . 403	34/40 (84%)
	scrofa, 404 aa.
	[WO9514096-A1,
	26-MAY-1995]

[0419] In a BLAST search of public sequence datbases, the NOV 13a protein was found to have homology to the proteins shown in the BLASTP data in Table 13E.

TABLE 13E
Public BLASTP Results for NOV13a
			Identities/
Protein			Similarities for
Accession		NOV13a Residues/	the Matched	Expect
Number	Protein/Organism/Length	Match Residues	Portion	Value
P15088	Mast cell carboxypeptidase A	1 . . . 44	43/44 (97%)	5e−17
	precursor (EC 3.4.17.1)	6 . . . 49	44/44 (99%)
	(MC-CPA) (Carboxypeptidase
	A3) - Homo sapiens (Human),
	417 aa.
P97597	Mast cell carboxypeptidase A	43 . . . 82	37/40 (92%)	1e−14
	precursor - Rattus norvegicus	373 . . . 412	39/40 (97%)
	(Rat), 412 aa (fragment).
P21961	Mast cell carboxypeptidase	43 . . . 82	37/40 (92%)	1e−14
	(EC 3.4. 17.1) (RMC-CP)	270 . . . 309	39/40 (97%)
	(Carboxypeptidase A3) - Rattus
	norvegicus (Rat), 309 aa.
P15089	Mast cell carboxypeptidase A	43 . . . 82	36/40 (90%)	7e−14
	precursor (EC 3.4.17.1)	378 . . . 417	39/40 (97%)
	(MC-CPA) (Carboxypeptidase
	A3) - Mus musculus (Mouse),
	417 aa.
P00732	Carboxypeptidase B (EC	41 . . . 80	26/40 (65%)	7e−11
	3.4.17.2) - Bos taurus (Bovine),	266 . . . 305	36/40 (90%)
	306 aa.

[0420] PFam analysis predicts that the NOV13a protein contains the domains shown in the Table 13F.

TABLE 13F
Domain Analysis of NOV13a
			Identities/
			Similarities
	Pfam	NOV13a	for the Matched	Expect
	Domain	Match Region	Region	Value
	Zn_carbOpept	41 . . . 65	16/30 (53%)	5.6e−08
			24/30 (80%)

Example 14

[0421] 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: 73	829 bp
NOV14a,	GCCCTTCGCGGGAGAGGAGGCCATGGGCGCGCGCGGGGCGCTGCTGCTGGCGCTGCTGCTGGCTCGG
CG144906-01
DNA Sequence	GCTGGACTCAGGAAGCCGGAGTCGCAGGAGGCGGCGCCCTTATCAGGACCATGCGGCCGACGGGTCA
	TCACGTCGCGCATCGTGGGTGGAGAGGACGCCGAACTCGGGCGTTGGCCGTGGCAGGGGAGCCTGCG
	CCTGTGGGATTCCCACGTATGCGGAGTGAGCCTGCTCAGCCACCGCTGGGCACTCACGGCGGCGCAC
	TGCTTTGAAACCTATAGTGACCTTAGTGATCCCTCCGGGTGGATGGTCCAGTTTGGCCAGCTGACTT
	CCATGCCATCCTCCACATTTGAGTTTGAGAACCGGACAGACTGCTGGGTGACTGGCTGGGGGTACAT
	CAAAGAGGATGAGGCACTGCCATCTCCCCACACCCTCCAGGAAGTTCAGGTCGCCATCATAAACAAC
	TCTATGTGCAACCACCTCTTCCTCAAGTACAGTTTCCGCAAGGACATCTTTGGAGACATGGTTTGTG
	CTGGCAATGCCCAAGGCGGGAAGGATGCCTGCTTCGGTGACTCAGGTGGACCCTTGGCCTGTAACAA
	GAATGGACTGTGGTATCAGATTGGAGTCGTGAGCTGGGGAGTGGGCTGTGGTCGGCCCAATCGGCCC
	GGTGTCTACACCAATATCAGCCACCACTTTGAGTGGATCCAGAAGCTGATGGCCCAGAGTGGCATGT
	CCCAGCCAGACCCCTCCTGGCCACTACTCTTTTTCCCTCTTCTCTGGGCTCTCCCACTCCTGGGGCC
	GGTCTGAGCCTACCTGAGCCCATGC
	ORF Start: ATG at 23		ORF Stop: TGA at 809
	SEQ ID NO: 74	262 aa	MW at 28826.7kD
NOV14a,	MGARGALLLALLLARAGLRKPESQEAAPLSGPCGRRVITSRIVGGEDAELGRWPWQGSLRLWDSHVC
CG144906-01
Protein Sequence	GVSLLSHRWALTAAHCFETYSDLSDPSGWMVQFGQLTSMPSSTFEFENRTDCWVTGWGYIKEDEALP
	SPHTLQEVQVAIINNSMCNHLFLKYSFRKDIFGDMVCAGNAQGGKDACFGDSGGPLACNKNGLWYQI
	GVVSWGVGCGRPNRPGVYTNISHHFEWIQKLMAQSGMSQPDPSWPLLFFPLLWALPLLGPV
	SEQ ID NO: 75	989 bp
NOV14b,	AATCGCCCTTCGCGGGAGAGGAGGCCATGGGCGCGCGCGGGGCGCTGCTGCTGGCGCTGCTGCTGGC
CG144906-02
DNA Sequence	TCGGGCTGGACTCAGGAAGCCGGAGTCGCAGGAGGCGGCGCCCTTATCAGGACCATGCGGCCGACGG
	GTCATCACGTCGCGCATCGTGGGTGGAGAGGACGCCGAACTCGGGCGTTGGCCGTGGCAGGGGAGCC
	TGCGCCTGTGGGATTCCCACGTATGCGGAGTGAGCCTGCTCAGCCACCGCTGGGCACTCACGGCGGC
	GCACTGCTTTGAAACCTATAGTGACCTTAGTGATCCCTCCGGGTGGATGGTCCAGTTTGGCCAGCTG
	ACTTCCATGCCATCCTTCTGGAGCCTGCAGGCCTACTACACCCGTTACTTCGTATCGAATATCTATC
	TGAGCCCTCGCTACCTGGGGAATTCACCCTATGACATTGCCTTGGTGAAGCTGTCTGCACCTGTCAC
	CTACACTAAACACATCCAGCCCATCTGTCTCCAGGCCTCCACATTTGAGTTTGAGAACCGGACAGAC
	TGCTGGGTGACTGGCTGGGGGTACATCAAAGAGGATGAGGCACTGCCATCTCCCCACACCCTCCAGG
	AAGTTCAGGTCGCCATCATAAACAACTCTATGTGCAACCACCTCTTCCTCAAGTACAGTTTCCGCAA
	GGACATCTTTGGAGACATGGTTTGTGCTGGCAATGCCCAAGGCGGGAAGGATGCCTGCTTCGGTGAC
	TCAGGTGGACCCTTGGCCTGTAACAGGAATGGACTGTGGTATCAGATTGGAGTCGTGAGCTGGGGAG
	TGGGCTGTGGTCGGCCCAATCGGCCCGGTGTCTACACCAATATCAGCCACCACTTTGAGTGGATCCA
	GAAGCTGATGGCCCAGAGTGGCATGTCCCAGCCAGACCCCTCCTGGCCACTACTCTTTTTCCCTCTT
	CTCTGGGCTCTCCCACTCCTGGGGCCGGTCTGAGCCTACCTTAGCCCATGC
	ORF Start: ATG at 27		ORF Stop: TGA at 969
	SEQ ID NO: 76	314 aa	MW at 34911.6kD
NOV14b,	MGARGALLLALLLARAGLRKPESQEAAPLSGPCGRRVITSRIVGGEDAELGRWPWQGSLRLWDSHVC
CG144906-02
Protein Sequence	GVSLLSHRWALTAAHCFETYSDLSDPSGWMVQFGQLTSMPSFWSLQAYYTRYFVSNIYLSPRYLGNS
	PYDIALVKLSAPVTYTKHIQPICLQASTFEFENRTDCWVTGWGYIKEDEALPSPHTLQEVQVAIINN
	SMCNHLFLKYSFRKDIFGDMVCAGNAQGGKDACFGDSGGPLACNRNGLWYQIGVVSWGVGCGRPNRP
	GVYTHISHHFEWIQKLMAQSGMSQPDPSWPLLFFPLLWALPLLGPV

[0422] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 14B.

TABLE 14B
Comparison of NOV14a against NOV14b.
		Identities/
	NOV14a Residues/	Similarities for
Protein Sequence	Match Residues	the Matched Region
NOV14b	20 . . . 240	219/273 (80%)
	20 . . . 292	221/273 (80%)

[0423] Further analysis of the NOV14a protein yielded the following properties shown in Table 14C.

TABLE 14C
Protein Sequence Properties NOV14a
PSort analysis:   0.5422 probability located in outside; 0.4639 probability located in lysosome
                  (lumen); 0.2779 probability located in microbody (peroxisome); 0.1900
                  probability located in plasma membrane
SignalP analysis: Cleavage site between residues 20 and 21

[0424] 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
		NOV14a
		Residues/	Identities/
Geneseq	Protein/Organism/Length	Match	Similarities for	Expect
Identifier	[Patent #, Date]	Residues	the Matched Region	Value
AAE17010	Human eosinophil serine	1 . . . 262	262/314 (83%)	e−154
	protease-1 (esp-1) like	1 . . . 314	262/314 (83%)
	enzyme #2 - Homo sapiens,
	314 aa.[WO200198503-A2,
	27-DEC-2001]
AAB80256	Human PR0303 protein -	1 . . . 262	262/314 (83%)	e−154
	Homo sapiens, 314 aa.	1 . . . 314	262/314 (83%)
	[WO200104311-A1,
	18-JAN-2001]
AAU01569	Human secreted protein	1 . . . 262	262/314 (83%)	e−154
	immunogenic epitope	1 . . . 314	262/314 (83%)
	encoded by gene #9 - Homo
	sapiens, 315 aa.
	[WO200123547-A1,
	05-APR-2001]
AAU02223	Human extracellular serine	1 . . . 262	262/314 (83%)	e−154
	protease TADG-16 - Homo	1 . . . 314	262/314 (83%)
	sapiens, 314 aa.
	[WO200127257-A1,
	19-APR-2001]
AAY91871	Human cancer-specific gene	1 . . . 262	262/314 (83%)	e−154
	protein, Pro104 - Homo	14 . . . 327	262/314 (83%)
	sapiens, 327 aa.
	[WO200016805-A1,
	30-MAR-2000]

[0425] 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
		NOV14a
Protein		Residues/	Identities/
Accession		Match	Similarities for	Expect
Number	Protein/Organism/Length	Residues	the Matched Portion	Value
Q9Y6MO	Testisin precursor (EC	1 . . . 262	262/314 (83%)	e−154
	3.4.21.-) (Eosinophil serine	1 . . . 314	262/314 (83%)
	protease 1) (ESP-1) - Homo
	sapiens (Human), 314 aa.
Q9JHJ7	Testisin precursor (EC	1 . . . 261	179/326 (54%)	1e−98
	3.4.21.-) (Tryptase 4) - Mus	1 . . . 323	210/326 (63%)
	musculus (Mouse), 324 aa.
Q920S2	Testis serine protease-1 - Mus	1 . . . 261	150/325 (46%)	2e−69
	musculus (Mouse), 322 aa.	1 . . . 321	180/325 (55%)
Q9D4I3	493l44OBO9Rik protein -	32 . . . 261	135/283 (47%)	1e−66
	Mus musculus (Mouse), 282	2 . . . 281	161/283 (56%)
	aa.
Q9PVX7	Epidermis specific serine	33 . . . 244	100/264 (37%)	3e−45
	protease - Xenopus Laevis	17 . . . 277	136/264 (50%)
	(African clawed frog), 389 aa.

[0426] PFam analysis predicts that the NOV14a protein contains the domains shown in the Table 14F.

TABLE 14F
Domain Analysis of NOV14a
		Identities/
Pfam		Similarities for	Expect
Domain	NOV14a Match Region	the Matched Region	Value
trypsin	42 . . . 85	24/51 (47%)	2.3e−13
		36/51 (71%)
trypsin	119 . . . 229	52/121 (43%)	9e−43
		92/121 (76%)

Example 15

[0427] 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:77	716 bp
NOV15a,	GAGTGAGCGATGAGCTGGTTTCTGTTCCTGGCCCACAGAGTCGCCTTGGCCGCCTTGCCCTGCCGCC
CG144997-01
DNA Sequence	GCGGCTCTCGCGGGTTCGGGATGTTCTATGCCGTGAGGAGGGGCCGCAAGACCGGGGTCTTTCTGAC
	CTGGAATGAGTGCAGAGACACGTTTTCCTACATGGGAGACTTCGTCGTCGTCTACACTGATGGCTGC
	TGCTCCAGTAATGGGCGTAGAAGGCCGCGAGCAGGAATCGGCGTTTACTGGGGGCCGGGCCATCCTT
	TAAATGTAGGCATTAGACTTCCTGGGCGGCAGACAAACCAAAGAGCGGAAATTCATGCAGCCTGCAA
	AGCCATTGAACAAGCAAAGACTCAAAACATCAATAAACTGGTTCTGTATACAGACAGTATGTTTACG
	ATAAATGGTATAACTAACTGGGTTCAAGGTTGGAAGAAAAATGGGTGGAAGACAAGTGCAGGGAAAG
	AGGTGATCAACAAAGAGGACTTTGTGGCACTGGAGAGGCTTACCCAGGGGATGGACATTCAGTGGAT
	GCATGTTCCTGGTCATTCGGGATTTATAGGCAATGAAGAAGCTGACAGATTAGCCAGAGAAGGAGCT
	AAACAATCGGAAGACTGAGCCATGTGACTTTAGTCCTTGGGAGAACTTGAGCCAGCGGCTGTCTTGC
	TGCCTGTACTTACTGGTGTGGAAAATAGCCTGCAGGTAGGACCATT
	ORF Start: ATG at 10		ORF Stop: TGA at 619
	SEQ ID NO: 78	203 aa	MW at 22889.0 kD
NOV15a,	MSWFLFLAHRVALAALPCRRGSRGFGMFYAVRRGRKTGVFLTWNECRDTFSYMGDFVVVYTDGCCSS
CG144997-01
Protein Sequence	NGRRRPRAGIGVYWGPGHPLNVGIRLPGRQTNQRAEIHAACKAIEQAKTQNINKLVLYTDSMFTING
	ITNWVQGWKKNGWKTSAGKEVINKEDFVALERLTQGMDIQWMHVPGHSGFIGNEEADRLAREGAKQS
	ED
	SEQ ID NO: 79	631 bp
NOV15b,	CACCGGATCCACCATGAGCTGGTTTCTGTTCCTGGCCCACAGAGTCGCCTTGGCCGCCTTGCCCTGC
278693648
DNA Sequence	CGCCGCGGCTCTCGCGGGTTCGGGATGTTCTATGCCGTGAGGAGGGGCCGCAAGACCGGGGTCTTTC
	TGACCTGGAATGAGTGCAGAGACACGTTTTCCTACATGGGAGACTTCGTCGTCGTCTACACTGATGG
	CTGCTGCTCCAGTAATGGGCGTAGAAGGCCGCGAGCAGGAATCGGCGTTTACTGGGGGCCGGGCCAT
	CCTTTAAATGTAGGCATTAGACTTCCTGGGCGGCAGACAAACCAAAGAGCGGAAATTCATGCAGCCT
	GCAAAGCCATTGAACAAGCAAAGACTCAAAACATCAATAAACTGGTTCTGTATACAGACAGTATGTT
	TACGATAAATGGTATAACTAACTGGGTTCAAGGTTGGAAGAAAAATGGGTGGAAGACAAGTGCAGGG
	AAAGAGGTGATCAACAAAGAGGACTTTGTGGCACTGGAGAGGCTTACCCAGGGGATGGACATTCAGT
	GGATGCATGTTCCTGGTCATTCGGGATTTATAGGCAATGAAGAAGCTGACAGATTAGCCAGAGAAGG
	AGCTAAACAATCGGAAGACCTCGAGGGC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO: 80	210 aa	MW at 23534.6 kD
NOV15b,	TGSTMSWFLFLAHRVALAALPCRRGSRGFGMFYAVRRGRKTGVFLTWNECRDTFSYMGDFVVVYTDG
278693648
Protein Sequence	CCSSNGRRRPRAGIGVYWGPGHPLNVGIRLPGRQTNQRAEIHAACKAIEQAKTQNINKLVLYTDSMF
	TINGITNWVQGWKKNGWKTSAGKEVINKEDFVALERLTQGMDIQWMHVPGHSGFIGNEEADRLAREG
	AKGSEDLEG
	SEQ ID NO: 81	586 bp
NOV15c,	CACCGGATCCGCCTTGCCCTGCCGCCGCGGCTCTCGCGGGTTCGGGATGTTCTATGCCGTGAGGAGG
278480974
DNA Sequence	GGCCGCAAGACCGGGGTCTTTCTGACCTGGAATGAGTGCAGAGACACGTTTTCCTACATGGGAGACT
	TCGTCGTCGTCTACACTGATGGCTGCTGCTCCAGTAATGGGCGTAGAAGGCCGCGAGCAGGAATCGG
	CGTTTACTGGGGGCCGGGCCATCCTTTAAATGTAGGCATTAGACTTCCTGGGCGGCAGACAAACCAA
	AGAGCGGAAATTCATGCAGCCTGCAAAGCCATTGAACAAGCAAAGACTCAAAACATCAATAAACTGG
	TTCTGTATACAGACAGTATGTTTACGATAAATGGTATAACTAACTGGGTTCAAGGTTGGAAGAAAAA
	TGGGTGGAAGACAAGTGCAGGGAAAGAGGTGATCAACAAAGAGGACTTTGTGGCACTGGAGAGGCTT
	ACCCAGGGGATGGACATTCAGTGGATGCATGTTCCTGGTCATTCGGGATTTATAGGCAATGAAGAAG
	CTGACAGATTAGCCAGAGAAGGAGCTAAACAATCGGAAGACCTCGAGGGC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO: 82	195 aa	MW at 21789.5 kD
NOV15c,	TGSALPCRRGSRGFGMFYAVRRGRKTGVFLTWNECRDTFSYMGDFVVVYTDGCCSSNGRRRPRAGIG
2784980974
Protein Sequence	VYWGPGHPLNVGIRLPGRQTNQRAEIHAACKAIEQAKTQNINKLVLYTDSMFTINGITNWVQGWKKN
	GWKTSAGKEVINKEDFVALERLTQGMDIQWMHVPGHSGFIGNEEADRLAREGAKQSEDLEG
	SEQ ID NO: 83	457 bp
NOV15d,	CAACGGATCCGGAGACTTCGTCGTCGTCTACACTGATGGCTGCTGCTCCAGTAATGGGCGTAGAAGG
278498047
DNA Sequence	CCGCGAGCAGGAATCGGCGTTTACTGGGGGCCGGGCCATCCTTTAAATGTAGGCATTAGACTTCCTG
	GGCGGCAGACAAACCAAAGAGCGGAAATTCATGCAGCCTGCAAAGCCATTGAACAAGCAAAGACTCA
	AAACATCAATAAACTGGTTCTGTATACAGACAGTATGTTTACGATAAATGGTATAACTAACTGGGTT
	CAAGGTTGGAAGAAAAATGGGTGGAAGACAAGTGCAGGGAAAGAGGTGATCAACAAAGAGGACTTTG
	TGGCACTGGAGAGGCTTACCCAGGGGATGGACATTCAGTGGATGCATGTTCCTGGTCATTCGGGATT
	TATAGGCAATGAAGAAGCTGACAGATTAGCCAGAGAAGGAGCTAAACTCGAGGGC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO: 84	152 aa	MW at 16753.8 kD
NOV15d,	TGSGDFVVVYTDGCCSSNGRRRPRAGIGVYWGPGHPLNVGIRLPGRQTNQRAEIHAACKAIEQAKTQ
278498047
Protein Sequence	NINKLVLYTDSMFTINGITNWVQGWKKNGWKTSAGKEVINKEDFVALERLTQGMDIQWMHVPGHSGF
	IGNEEADRLAREGAKLEG
	SEQ ID NO: 85	965 bp
NOV15e,	GAGTGAGCGATGAGCTGGTTTCTGTTCCTGGCCCACAGAGTCGCCTTGGCCGCCTTGCCCTGCCGCC
CG144997-02
DNA Sequence	GCGGCTCTCGCGGGTTCGGGATGTTCTATGCCGTGAGGAGGGGCCGCAAGACCGGGGTCTTTCTGAC
	CTGGAATGAGTGCAGAGCACAGGTGGACCGGTTTCCTGCTGCCAGATTTAAGAAGTTTGCCACAGAG
	GATGAGGCCTGGGCCTTTGTCAGGAAATCTGCAAGCCCGGAAGTTTCAGAAGGGCATGAAAATCAAC
	ATGGACAAGAATCGGAGGCGAAAGCCAGCAAGCGACTCCGTGAGCCACTGGATGGAGATGGACATGA
	AAGCGCAGAGCCGTATGCAAAGCACATGAAGCCGAGCGTGGAGCCGGCGCCTCCAGTTAGCAGAGAC
	ACGTTTTCCTACATGGGAGACTTCGTCGTCGTCTACACTGATGGCTGCTGCTCCAGTAATGGGCGTA
	GAAGGCCGCGAGCAGGAATCGGCGTTTACTGGGGGCCAGGCCATCCTTTAAATGTAGGCATTAGACT
	TCCTGGGCGGCAGACAAACCAAAGAGCGGAAATTCATGCAGCCTGCAAAGCCATTGAACAAGCAAAG
	ACTCAAAACATCAATAAACTGGTTCTGTATACAGACAGTATGTTTACGATAAATGGTATAACTAACT
	GGGTTCAAGGTTGGAAGAAAAATGGGTGGAAGACAAGTGCAGGGAAAGAGGTGATCAACAAAGAGGA
	CTTTGTGGCACTGGAGAGGCTTACCCAGGGGATGGACATTCAGTGGATGCATGTTCCTGGTCATTCG
	GGATTTATAGGCAATGAAGAAGCTGACAGATTAGCCAGAGAAGGAGCTAAACAATCGGAAGACTGAG
	CCATGTGACTTTAGTCCTTGGGAGAACTTGAGCCAGCGGCTGTCTTGCTGCCTGTACTTACTGGTGT
	GGAAAATAGCCTGCAGGTAGGACCATT
	ORF Start: ATG at 10		ORF Stop: TGA at 868
	SEQ ID NO:86	286aa	MW at 32098.0kD
NOV15e,	MSWFLFLAHRVALAALPCRRGSRGFGMFYAVRRGRKTGVFLTWNECRAQVDRFPAARFKKFATEDEA
CG144997-02
Protein Sequence	WAFVRKSASPEVSEGHENQHGQESEAKASKRLREPLDGDGHESAEPYAKHMKPSVEPAPPVSRDTFS
	YMGDFVVVYTDGCCSSNGRRRPRAGIGVYWGPGHPLNVGIRLPGRQTNQRAEIHAACKAIEQAKTQN
	INKLVLYTDSMFTINGITNWVQGWKKNGWKTSAGKEVINKEDFVALERLTQGMDIQWMHVPGHSGFI
	GNEEADRLAREGAKQSED

[0428] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 15B.

TABLE 15B
Comparison of NOV15a against NOV15b through NOV15e.
		Identities/
	NOV15a Residues/	Similarities for
Protein Sequence	Match Residues	the Matched Region
NOV15b	1 . . . 203	203/203 (100%)
	5 . . . 207	203/203 (100%)
NOV15c	14 . . . 203	189/190 (99%)
	3 . . . 192	190/190 (99%)
NOV15d	54 . . . 199	146/146 (100%)
	4 . . . 149	146/146 (100%)
NOV15e	47 . . . 203	157/157 (100%)
	130 . . . 286	157/157 (100%)

[0429] Further analysis of the NOV15a protein yielded the following properties shown in Table 15C.

TABLE 15C
Protein Sequence Properties NOV15a
PSort analysis:   0.3700 probability located in outside; 0.1805 probability located in microbody
                  (peroxisome); 0.1080 probability located in nucleus; 0.1000 probability
                  located in endoplasmic reticulum (membrane)
SignalP analysis: Cleavage site between residues 15 and 16

[0430] A search of the NOV15a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 15D.

TABLE 15D
Geneseq Results for NOV15a
		NOV15a
		Residues/	Identities/
Geneseq	Protein/Organism/Length	Match	Similarities for	Expect
Identifier	[Patent #, Date]	Residues	the Matched Region	Value
AAY70235	Human RNA-associated	47 . . . 203	157/157 (100%)	6e−92
	protein-16 (RNAAP-16) -	130 . . . 286	157/157 (100%)
	Homo sapiens, 286 aa.
	[WO200011171-A2,
	02-MAR-2000]
AAB97508	Human type II RNase H	47 . . . 203	156/157 (99%)	1e−91
	protein - Homo sapiens, 286	130 . . . 286	157/157 (99%)
	aa. [WPO200123613-A1,
	05-APR-2001]
AAY25094	Human type 2 RNase H	47 . . . 203	156/157 (99%)	1e−91
	protein - Homo sapiens, 286	130 . . . 286	157/157 (99%)
	aa. [WO9928447-A1,
	10-JUN-1999]
ABB83371	Human wild-type RNase H1 -	47 . . . 203	156/157 (99%)	2e−90
	Homo sapiens, 286 aa.	130 . . . 286	156/157 (99%)
	[WO200240635-A2,
	23-MAY-2002]
ABB83374	Mutant RNase H1, E186Q -	47 . . . 203	155/157 (98%)	5e−90
	Homo sapiens, 286 aa.	130 . . . 286	156/157 (98%)
	[WO200240635-A2,
	23-MAY-2002]

[0431] 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 15E.

TABLE 15E
Public BLASTP Results for NOV15a
		NOV15a
Protein		Residues/	Identities/
Accession		Match	Similarities for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
O60930	Ribonuclease H1 (EC	47 . . . 203	157/157 (100%)	2e−91
	3.1.26.4) (RNase H1)	130 . . . 286	157/157 (100%)
	(Ribonuclease H type II) -
	Homo sapiens (Human), 286
	aa.
Q8VCR6	Ribonuclease H1 - Mus	47 . . . 203	139/157 (88%)	5e−83
	musculus (Mouse), 285 aa.	129 . . . 285	150/157 (95%)
O70338	Ribonuclease H1 (EC	47 . . . 203	139/157 (88%)	5e−83
	3.1.26.4) (RNase H1) - Mus	129 . . . 285	150/157 (95%)
	musculus (Mouse), 285 aa.
Q91953	mRNA, complete cds, clone	50 . . . 202	117/153 (76%)	4e−70
	CLFEST65 - Gallus gallus	140 . . . 292	135/153 (87%)
	(Chicken), 293 aa.
Q21024	F59A6.6 protein -	58 . . . 199	65/142 (45%)	3e−32
	Caenorhabditis elegans, 369	222 . . . 363	93/142 (64%)
	aa.

[0432] PFam analysis predicts that the NOV15a protein contains the domains shown in the Table 15F.

TABLE 15F
Domain Analysis of NOV15a
		Identities/
Pfam		Similarities	Expect
Domain	NOV15a Match Region	for the Matched Region	Value
rnaseH	54 . . . 199	65/176 (37%)	2.8e−54
		125/176 (71%)

Example 16

[0433] 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: 87	2274 bp
NOV 16a,	CCCCTAGTGACACTCAGGAAATGCTTGTCTCCGGCTGTTAAGGAATAATTTCAGAGTACTATGGATC
CG145494-01
DNA Sequence	ATGCTGAAGAAAATGAAATCCTTGCAGCAACCCAGAGGTACTATGTGGAAAGGCCTATCTTTAGTCA
	TCCGGTCCTCCAGGAAAGACTACACACAAAGGACAAGGTTCCTGATTCCATTGCGGATAAGCTGAAA
	CAGGCATTCACATGTACTCCTAAAAAAATAAGAAATATCATTTATATGTTCCTACCCATAACTAAAT
	GGCTGCCAGCATACAAATTCAAGGAATATGTGTTGGGTGACTTGGTCTCAGGCATAAGCACAGGGGT
	GCTTCAGCTTCCTCAAGGCTTAGCCTTTGCAATGCTGGCAGCTGTGCCTCCAATATTTGGCCTGTAC
	TCTTCATTTTACCCTGTTATCATGTATTGTTTTCTTGGAACCTCCAGACACATATCCATAGGTCCTT
	TTGCTGTTATTAGCCTGATGATTGGTGGTGTAGCTGTTCGATTAGTACCAGATGATATAGTCATTCC
	AGGAGGAGTAAATGCAACCAATGGCACAGAGGCCAGAGATGCCTTGAGAGTGAAAGTCGCCATGTCT
	GTGACCTTACTTTCAGGAATCATTCAGTTTTGCCTAGGTGTCTGTAGGTTTGGATTTGTGGCCATAT
	ATCTCACAGAGCCTCTGGTCCGTGGGTTTACCACCGCAGCAGCTGTGCATGTCTTCACCTCCATGTT
	AAAATATCTGTTTGGAGTTAAAACAAAGCGGTACAGTGGAATCTTTTCCGTGGTGTATAGTACAGTT
	GCTGTGTTGCAGAATGTTAAAAACCTCAACGTGTGTTCCCTAGGCGTCGGGCTGATGGTTTTTGGTT
	TGCTGTTGGGTGGCAAGGAGTTTAATGAGAGATTTAAAGAGAAATTGCCGGCGCCTATTCCTTTAGA
	GTTCTTTGCGGTCGTAATGGGAACTGGCATTTCAGCTGGGTTTAACTTGAAAGAATCATACAATGTG
	GATGTCGTTGGAACACTTCCTCTAGGGCTGCTACCTCCAGCCAATCCGGACACCAGCCTCTTCCACC
	TTGTGTACGTAGATGCCATTGCCATAGCCATCGTTGGATTTTCAGTGACCATCTCCATGGCCAAGAC
	CTTAGCAAATAAACATGGCTACCAGGTTGACGGCAATCAGGAGCTCATTGCCCTGGGACTGTGCAAT
	TCCATTGGCTCACTCTTCCAGACCTTTTCAATTTCATGCTCCTTGTCTCGAAGCCTTGTTCAGGAGG
	GAACCGGTGGGAAGACACAGGCTGTGCTGTCGGCCATTGTGATTGTCAACCTGAAGGGAATGTTTAT
	GCAGTTCTCAGATCTCCCCTTTTTCTGGAGAACCAGCAAAATAGAGCTGACCATCTGGCTTACCACT
	TTTGTGTCCTCCTTGTTCCTGGGATTGGACTATGGTTTGATCACTGCTGTGATCATTGCTCTGCTGA
	CTGTGATTTACAGAACACAGAGTCCAAGCTACAAAGTCCTTGGAAAGCTTCCTGAAACTGATGTGTA
	TATTGATATAGACGCATATGAGGAGGTGAAAGAAATTCCTGGAATAAAAATATTTCAAATAAATGCA
	CCAATTTACTATGCAAATAGCGACTTGTATAGCAATGCATTAAAACGAAAGACTGGAGTGAACCCAG
	CAGTCATCATGGGAGCAAGGAGAAAGGCCATGCGGAAGTACGCTAAGGAAGTCGGAAATGCAAATAT
	GGCCAACGCAACTGTTGTCAAAGCAGATGCAGAAGTAGATGGAGAGGATGCTACCAAGCCTGAAGAA
	GAGGATGGTGAAGTAAAATATCCCCCAATAGTGATCAAAAGCACATTTCCTGAGGAAATGCAAAGAT
	TTATGCCCCCAGGGGATAACGTCCACACTGTCATTTTGGATTTCACTCAAGTCAATTTTATTGATTC
	TGTTGGAGTGAAAACTCTGGCAGGGATTGTAAAAGAATATGGAGACGTCGGTATATATGTATACTTA
	GCAGGATGCAGTGCACAAGTTGTGAATGACCTCACTCGGAATAGATTTTTTGAAAATCCTGCCCTAT
	GGGAGCTGCTGTTCCACAGCATTCATGATGCAGTTTTAGGCAGCCAACTTAGAGAGGCACTTGCTGA
	ACAGGAAGCCTCGGCTCCCCCTTCCCAGGAGGACTTGGAGCCCAATGCCACTCCTGCCACTCCTGAG
	GCATAGATGAGGACCTCACCCTAGGATGGGGTTATAAGCCTCTCATGAAGTTCATAATTTACA
	ORF Start: ATG at 61		ORF Stop: TAG at 2215
	SEQ ID NO: 88	718 aa	MW at 78546.4 kD
NOV 16a,	MDHAEENEILAATQRYYVERPIFSHPVLQERLHTKDKVPDSIADKLKQAFTCTPKKIRNIIYMFLPI
CG145494-01
Protein Sequence	TKWLPAYKFKEYVLGDLVSGISTGVLQLPQGLAFAMLAAVPPIFGLYSSFYPVIMYCFLGTSRHISI
	GPFAVISLMIGGVAVRLVPDDIVIPGGVNATNGTEARDALRVKVAMSVTLLSGIIQFCLGVCRFGFV
	AIYLTEPLVRGFTTAAAVHVFTSMLKYLFGVKTKRYSGIFSVVYSTVAVLQNVKNLNVCSLGVGLMV
	FGLLLGGKEFNERFKEKLPAPIPLEFFAVVMGTGISAGFNLKESYNVDVVGTLPLGLLPPANPDTSL
	FHLVYVDAIAIAIVGFSVTISMAKTLANKHGYQVDGNQELIALGLCNSIGSLFQTFSISCSLSRSLV
	QEGTGGKTQAVLSAIVIVNLKGMFMQFSDLPFFWRTSKIELTIWLTTFVSSLFLGLDYGLITAVIIA
	LLTVIYRTQSPSYKVLGKLPETDVYIDIDAYEEVKEIPGIKIFQINAPIYYANSDLYSNALKRKTGV
	NPAVIMGARRKAMRKYAKEVGNANMANATVVKADAEVDGEDATKPEEEDGEVKYPPIVIKSTFPEEM
	QRFMPPGDNVHTVILDFTQVNFIDSVGVKTLAGIVKEYGDVGIYVYLAGCSAQVVNDLTRNRFFENP
	ALWELLFHSIHDAVLGSQLREALAEQEASAPPSQEDLEPNATPATPEA

[0434] Further analysis of the NOV16a protein yielded the following properties shown in Table 16B.

TABLE 16B
Protein Sequence Properties NOV16a
PSort analysis:   0.6000 probability located in plasma membrane; 0.4000 probability located in
                  Golgi body; 0.3200 probability located in nucleus; 0.3000 probability located
                  in endoplasmic reticulum (membrane)
SignalP analysis: No Known Signal Sequence Predicted

[0435] A search of the NOV16a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 16C.

TABLE 16C
Geneseq Results for NOV16a
		NOV16a
Residues/	Identities/
Geneseq	Protein/Organism/Length	Match	Similarities for	Expect
Identifier	[Patent #, Date]	Residues	the Matched Region	Value
AAY71067	Human membrane transport	9 . . . 684	291/741 (39%)	e−148
	protein, MTRP-12 - Homo	15 . . . 738	433/741 (58%)
	sapiens, 758 aa.
	[WO200026245-A2,
	11-MAY-2000]
AAG67162	Amino acid sequence of a	9 . . . 684	289/734 (39%)	e−147
	human 32613 transporter	15 . . . 731	432/734 (58%)
	polypeptide - Homo sapiens,
	751 aa. [WO200164875-A2,
	07-SEP-2001]
ABG61914	Prostate cancer-associated	16 . . . 699	268/723 (37%)	e−144
	protein #115 - Mammalia,	20 . . . 741	419/723 (57%)
	790 aa. [WO200230268-A2,
	18-APR-2002]
AAM51696	Human pendrin SEQ ID NO	16 . . . 699	268/723 (37%)	e−144
	2 - Homo sapiens, 780 aa.	20 . . . 741	419/723 (57%)
	[JP2001228146-A,
	24-AUG-2001]
AAM51695	Mouse pendrin SEQ ID	16 . . . 688	270/713 (37%)	e−142
	NO 1 - Mus sp, 780 aa.	20 . . . 730	414/713 (57%)
	[JP2001228146-A,
	24-AUG-2001]

[0436] In a BLAST search of public sequence datbases, the NOV16a protein was found to have homology to the proteins shown in the BLASTP data in Table 16D.

TABLE 16D
Public BLASTP Results for NOV16a
		NOV16a
Protein		Residues/	Identities/
Accession		Match	Similarities for	Expect
Number	Protein/Organism/Length	Residues	the Matched Portion	Value
P58743	Prestin - Homo sapiens	1 . . . 718	718/744 (96%)	0.0
	(Human), 744 aa.	1 . . . 744	718/744 (96%)
Q9JKQ2	Prestin - Meriones	1 . . . 718	679/744 (91%)	0.0
	unguiculatus (Mongolian	1 . . . 744	699/744 (93%)
	jird) (Mongolian gerbil), 744
	aa.
Q99NH7	Prestin - Mus musculus	1 . . . 718	680/744 (91%)	0.0
	(Mouse), 744 aa.	1 . . . 744	700/744 (93%)
Q9EPH0	Prestin - Rattus norvegicus	1 . . . 718	677/744 (90%)	0.0
	(Rat), 744 aa.	1 . . . 744	699/744 (92%)
AAH28856	Solute carrier family 26,	16 . . . 684	282/718 (39%)	e−148
	member 6 - Mus musculus	8 . . . 715	432/718 (59%)
	(Mouse), 735 aa.

[0437] PFam analysis predicts that the NOV16a protein contains the domains shown in the Table 16E.

TABLE 16E
Domain Analysis of NOV16a
		Identities/
		Similarities
		for the	Expect
Pfam Domain	NOV16a Match Region	Matched Region	Value
COX3	334 . . . 458	31/266 (12%)	0.7
		80/266 (30%)
Sulfate_transp	191 . . . 477	111/328 (34%)	7e−78
		234/328 (71%)
STAS	500 . . . 683	34/188 (18%)	1.4e−12
		124/188 (66%)

Example 17

[0438] 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: 89	2124 bp
NOV 17a,	AAGCTGAGGTCTTATAGATTGGTGGTACTTAAGGCAGAAAATTAACACCGTGTTTTGTAGCTGTTAG
CG145722-01
DNA Sequence	TTGGTAGAGGGAAATTCAGGCTACCGTCGCGAAACCTGCAGGTTAAGTTATTTTCTCCTCCCTGCTT
	CTGTAGGTTCACAGCGTTCCCTTCTGATAGAGCTTTTTGTCTGTGTTGTAAAGCTCTTTGGCTGAGA
	TGGATGACAAAGATATTGACAAAGAACTAAGGCAGAAATTAAACTTTTCCTATTGTGAGGAGACTGA
	GATTGAAGGGCAGAAGAAAGTAGAAGAAAGCAGGGAGGCTTCGAGCCAAACCCCAGAGAAGGGTGAA
	GTGCAGGATTCAGAGGCAAAGGGTACACCACCTTGGACTCCCCTTAGCAACGTGCATGAGCTCGACA
	CATCTTCGGAAAAAGACAAAGAAAGTCCAGATCAGATTTTGAGGACTCCAGTGTCACACCCTCTCAA
	ATGTCCTGAGACACCAGCCCAACCAGACAGCAGGAGCAAGCTGCTGCCCAGTGACAGCCCCTCTACT
	CCCAAAACCATGCTGAGCCGGTTGGTGATTTCTCCAACAGGGAAGCTTCCTTCCAGAGGCCCTAAGC
	ATTTGAAGCTCACACCTGCTCCCCTCAAGGATGAGATGACCTCATTGGCTCTGGTCAATATTAATCC
	CTTCACTCCAGAGTCCTATAAAAAATTATTTCTTCAATCTGGTGGCAAGAGGAAAATAAGAAGATGT
	GTTTTACGAGAAACCAACATGGCTTCCCGCTATGAAAAAGAATTCTTGGAGGTTGAAAAAATTGGGG
	TTGGCGAATTTGGTACAGTCTACAAGTGCATTAAGAGGCTGGATGGATGTGTTTATGCAATAAAGCG
	CTCTATGAAAACTTTTACAGAATTATCAAATGAGAATTCGGCTTTGCATGAAGTTTATGCTCACGCA
	GTGCTTGGGCATCACCCCCATGTGGTACGTTACTATTCCTCATGGGCAGAAGATGACCACATGATCA
	TTCAGAATGAATACTGCAATGGTGGGAGTTTGCAAGCTGCTATATCTGAAAACACTAAGTCTGGCAA
	TCATTTTGAAGAGCCAAAACTCAAGGACATCCTTCTACAGATTTCCCTTGGCCTTAATTACATCCAC
	AACTCTAGCATGGTACACCTGGACATCAAACCTAGTAATATATTCATTTGTCACAAGATGCAAAGTG
	AATCCTCTGGAGTCATAGAAGAAGTTGAAAATGAAGCTGATTGGTTTCTCTCTGCCAATGTGATGTA
	TAAAATTGGTGACCTGGGCCACGCAACATCAATAAACAAACCCAAAGTGGAAGAAGGAGATAGTCGC
	TTCCTGGCTAATGAGATTTTGCAAGAGGATTACCGGCACCTTCCCAAAGCAGACATATTTGCCTTGG
	GATTAACAATTGCAGTGGCTGCAGGAGCAGAGTCATTGCCCACCAATGGTGCTGCATGGCACCATAT
	CCGCAAGGGTAACTTTCCGGACGTTCCTCAGGAGCTCTCAGAAAGCTTTTCCAGTCTGCTCAAGAAC
	ATGATCCAACCTGATGCCGAACAGAGACCTTCTGCAGCAGCTCTGGCCAGAAATACAGTTCTCCGGC
	CTTCCCTGGGAAAAACAGAAGAGCTCCAACAGCAGCTGAATTTGGAAAAGTTCAAGACTGCCACACT
	GGAAAGGGAACTGAGAGAAGCCCAGCAGGCCCAGTCACCCCAGGGATATACCCATCATGGTGACACT
	GGGGTCTCTGGGACCCACACAGGATCAAGAAGCACAAAACGCCTGGTGGGAGGAAAGAGTGCAAGGT
	CTTCAAGCTTTACCTGTGAGTAATCTTCCCCTTAAGAACTCATTTTGCAGCCGGGCGTGGTGGCTCA
	CGCCTGTAATCCCAACACTTTGGGAGGCCAAGGCAGGTGGATCATGAGGTCAGGAGATCGAAACCAT
	CCTGGCTAACACGGTGAAACCCCATCTCTACTAAAAATACAAAAAATTAGCAGGGCGAGGTGGCAGG
	CGCCTATAATCCCAGCTACTCAGGAGGCTGAGGAAGGAGAATCGCTTGAACCCGGGAGGTGGAGCTT
	GCAGTGAGCTGAGATCACACCACTGCACTCCAGCCTGGGCAACAGAG
	ORF Start: ATG at 201		ORF Stop: TAA at 1830
	SEQ ID NO: 90	543 aa	MW at 60514.5 kD
NOV 17a,	MDDKDIDKELRQKLNFSYCEETEIEGQKKVEESREASSQTPEKGEVQDSEAKGTPPWTPLSNVHELD
CG 145722-01
Protein Sequence	TSSEKDKESPDQILRTPVSHPLKCPETPAQPDSRSKLLPSDSPSTPKTMLSRLVISPTGKLPSRGPK
	HLKLTPAPLKDEMTSLALVNINPFTPESYKKLFLQSGGKRKIRRCVLRETNMASRYEKEFLEVEKIG
	VGEFGTVYKCIKRLDGCVYAIKRSMKTFTELSNENSALHEVYAHAVLGHHPHVVRYYSSWAEDDHMI
	IQNEYCNGGSLQAAISENTKSGNHFEEPKLKDILLQISLGLNYIHNSSMVHLDIKPSNIFICHKMQS
	ESSGVIEEVENEADWFLSANVMYKIGDLGHATSINKPKVEEGDSRFLANEILQEDYRHLPKADIFAL
	GLTIAVAAGAESLPTNGAAWHHIRKGNFPDVPQELSESFSSLLKNMIQPDAEQRPSAAALARNTVLR
	PSLGKTEELQQQLNLEKFKTATLERELREAQQAQSPQGYTHHGDTGVSGTHTGSRSTKRLVGGKSAR
	SSSFTCE

[0439] Further analysis of the NOV17a protein yielded the following properties shown in Table 17B.

TABLE 17B
Protein Sequence Properties NOV17a
PSort analysis:   0.4500 probability located in cytoplasm; 0.3000 probability located in
                  microbody (peroxisome); 0.1000 probability located in mitochondrial matrix
                  space; 0.1000 probability located in lysosome (lumen)
SignalP analysis: No Known Signal Sequence Predicted

[0440] A search of the NOV17a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 17C.

TABLE 17C
Geneseq Results for NOV17a
Geneseq	Protein/Organism/Length	NOV 17a Residues/	Identities/Similarities	Expect
Identifier	[Patent #, Date]	Match Residues	for the Matched Region	Value
AAB62519	Xenopus Wee1 protein	188 . . . 431	170/244 (69%)	1e−94
	catalytic domain (residues	1 . . . 240	191/244 (77%)
	210-443) - Xenopus sp, 240
	aa. [US6225101-B1,
	01-MAY-2001]
AAY51401	Xenopus sp. Wee1 catalytic	188 . . . 431	170/244 (69%)	1e−94
	domain protein fragment -	1 . . . 240	191/244 (77%)
	Xenopus sp, 240 aa.
	[US6020194-A,
	01-FEB-2000]
ABB60693	Drosophila melanogaster	109 . . . 501	180/464 (38%)	9e−78
	polypeptide SEQ ID NO	101 . . . 551	257/464 (54%)
	8871 - Drosophila
	melanogaster, 609 aa.
	[WO200171042-A2,
	27-SEP-2001]
AAY96776	Z. mays partial wee1 kinase -	185 . . . 465	103/282 (36%)	3e−45
	Zea mays, 525 aa.	264 . . . 513	153/282 (53%)
	[WO200037645-A2,
	29-JUN-2000]
AAY96770	Z. mays partial wee1 kinase -	185 . . . 465	103/282 (36%)	3e−45
	Zea mays, 403 aa.	142 . . . 391	153/282 (53%)
	[WO200037645-A2,
	29-JUN-2000]

[0441] In a BLAST search of public sequence datbases, the NOV 17a protein was found to have homology to the proteins shown in the BLASTP data in Table 17D.

TABLE 17D
Public BLASTP Results for NOV17a
Protein
Accession		NOV17a Residues/	Identities/Similarities	Expect
Number	Protein/Organism/Length	Match Residues	for the Matched Portion	Value
O95017	WUGSC:H_DJ0894A10.2	1 . . . 541	541/541 (100%)	0.0
	protein - Homo sapiens	1 . . . 541	541/541 (100%)
	(Human), 541 aa (fragment).
P47817	Wee1-like protein kinase (EC	10 . . . 542	291/560 (51%)	e−143
	2.7.1.112) - Xenopus laevis	11 . . . 552	352/560 (61%)
	(African clawed frog), 555
	aa.
O57473	Wee1 homolog - Xenopus	10 . . . 542	294/566 (51%)	e−143
	laevis (African clawed frog),	11 . . . 551	357/566 (62%)
	554aa.
Q8QGV2	Wee1B kinase - Xenopus	10 . . . 541	263/579 (45%)	e−122
	laevis (African clawed frog),	20 . . . 593	350/579 (60%)
	595 aa.
Q63802	Wee1-like protein kinase (EC	92 . . . 541	236/484 (48%)	e−118
	2.7.1.112) -Rattus	168 . . . 644	308/484 (62%)
	norvegicus (Rat), 646 aa.

[0442] PFam analysis predicts that the NOV 17a protein contains the domains shown in the Table 17E.

TABLE 17E
Domain Analysis of NOV17a
	NOV17a	Identities/Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
pkinase	194 . . . 462	73/310 (24%)	6.4e−45
		193/310 (62%)

Example 18

[0443] 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 91	753 bp
NOV18a,	TCCCTTCTCCTGCCCCTGCAGATCCTACTGCTATCCTTAGCCTTGGAAACTGCAGGAGAAGAAGCCC
CG145754-01
DNA Sequence	AGGGTGACAAGATTATTGATGGCGCCCCATGTGCAAGAGGCTCCCACCCATGGCAGGTGGCCCTGCT
	CAGTGGCAATCAGCTCCACTGCGGAGGCGTCCTGGTCAATGAGCGCTGGGTGCTCACTGCCGCCCAC
	TGCAAGATGAATGAGTACACCGTGCACCTGGGCAGTGATACGCTGGGCGACAGGAGAGCTCAGAGGA
	TCAAGGCCTCGAAGTCATTCCGCCACCCCGGCTACTCCACACAGACCCATGTTAATGACCTCATGCT
	CGTGAAGCTCAATAGCCAGGCCAGGCTGTCATCCATGGTGAAGAAAGTCAGGCTGCCCTCCCGCTGC
	GAACCCCCTGGAACCACCTGTACTGTCTCCGGCTGGGGCACTACCACGAGCCCAGATGTGACCTTTC
	CCTCTGACCTCATGTGCGTGGATGTCAAGCTCATCTCCCCCCAGGACTGCACGAAGGTTTACAAGGA
	CTTACTGGAAAATTCCATGCTGTGCGCTGGCATCCCCGACTCCAAGAAAAACGCCTGCAATGGTGAC
	TCAGGGGGACCGTTGGTGTGCAGAGGTACCCTGCAAGGTCTGGTGTCCTGGGGAACTTTCCCTTGCG
	GCCAACCCAATGACCCAGGAGTCTACACTCAAGTGTGCAAGTTCACCAAGTGGATAAATGACACCAT
	GAAAAAGCATCGCTAA
	ORF Start: at 1		ORF Stop: TAA at 751
	SEQ ID NO: 92	250 aa	MW at 27166.0 kD
NOV18a,	SLLLPLQILLLSLALETAGEEAQGDKIIDGAPCARGSHPWQVALLSGNQLHCGGVLVNERWVLTAAH
CG145754-01
Protein Sequence	CKMNEYTVHLGSDTLGDRRAQRIKASKSFRHPGYSTQTHVNDLMLVKLNSQARLSSMVKKVRLPSRC
	EPPGTTCTVSGWGTTTSPDVTFPSDLMCVDVKLISPODCTKVYKDLLENSMLCAGIPDSKKNACNGD
	SGGPLVCRGTLQGLVSWGTFPCGQPNDPGVYTQVCKFTKWINDTMKKHR
	SEQ ID NO:93	862 bp
NOV18b,	ACTGGGTCCGAATCAGTAGGTGACCCCGCCCCTGGATTCTGGAAGACCTCACCATGGGACGCCCCCG
CG145754-03
DNA Sequence	ACCTCGTGCGGCCAAGACGTGGATGTTCCTGCTCTTACTGGGGGGAGCCTGGGCAGCCAGGGGTGAC
	AAGATTATTGATGGCGCCCCATGTGCAAGAGGCTCCCACCCATGGCAGGTGGCCCTGCTCAGTGGCA
	ATCAGCTCCACTGCGGAGGCGTCCTGGTCAATGAGCGCTGGGTGCTCACTGCCGCCCACTGCAAGAT
	GAATGAGTACACCGTGCACCTGGGCAGTGATACGCTGGGCGACAGGAGAGCTCAGAGGATCAAGGCC
	TCGAAGTCATTCCGCCACCCCGGCTACTCCACACAGACCCATGTTAATGACCTCATGCTCGTGAAGC
	TCAATAGCCAGGCCAGGCTGTCATCCATGGTGAAGAAAGTCAGGCTGCCCTCCCGCTGCGAACCCCC
	TGGAACCACCTGTACTGTCTCCGGCTGGGGCACTACCACGAGCCCAGATGTGACCTTTCCCTCTGAC
	CTCATGTGCGTGGATGTCAAGCTCATCTCCCCCCAGGACTGCACGAAGGTTTACAAGGACTTACTGG
	AAAATTCCATGCTGTGCGCTGGCATCCCCGACTCCAAGAAAAACGCCTGCAATGGTGACTCAGGGGG
	ACCGTTGGTGTGCAGAGGTACCCTGCAAGGTCTGGTGTCCTGGGGAACTTTCCCTTGCGGCCAACCC
	AATGACCCAGGAGTCTACACTCAAGTGTGCAAGTTCACCAAGTGGATAAATGACACCATGAAAAAGC
	ATCGCTAACGCCACACTGAGTTAATTAACTGTGTGCTTCCAACAGAAAATGCACAGGA
	ORF Start: ATG at 54		ORF Stop: TAA at 810
	SEQ ID NO: 94	252 aa	MW at 27557.6 kD
NOV18b,	MGRPRPRAAKTWMFLLLLGGAWAARGDKIIDGAPCARGSHPWQVALLSGNQLHCGGVLVNERWVLTA
CG145754-03
Protein Sequence	AHCKMNEYTVHLGSDTLGDRRAQRIKASKSFRHPGYSTQTHVNDLMLVKLNSQARLSSMVKKVRLPS
	RCEPPGTTCTVSGWGTTTSPDVTFPSDLMCVDVKLISPQDCTKVYKDLLENSMLCAGIPDSKKNACN
	GDSGGPLVCRGTLQGLVSWGTFPCGQPNDPGVYTQVCKFTKWINDTMKKHR
	SEQ ID NO:95	804 bp
NOV18c,	GGATTTCCGGGCTCCATGGCAAGATCCCTTCTCCTGCCCCTGCAGATCCTACTGCTATCCTTAGCCT
CG145754-02
DNA Sequence	TGGAAACTGCAGGAGAAGAAGCCCAGGGTGACAAGATTATTGATGGCGCCCCATGTGCAAGAGGCTC
	CCACCCATGGCAGGTGGCCCTGCTCAGTGGCAATCAGCTCCACTGCGGAGGCGTCCTGGTCAATGAG
	CGCTGGGTGCTCACTGCCGCCCACTGCAAGATGAATGAGTACACCGTGCACCTGGGCAGTGATACGC
	TGGGCGACAGGAGAGCTCAGAGGATCAAGGCCTCGAAGTCATTCCGCCACCCCGGCTACTCCACACA
	GACCCATGTTAATGACCTCAAGCTCATCTCCCCCCAGGACTGCACGAAGGTTTACAAGGACTTACTG
	GAAAATTCCATGCTGTGCGCTGGCATCCCCGACTCCAAGAAAAACGCCTGCAATGGTGACTCAGGGG
	GACCGTTGGTGTGCAGAGGTACCCTGCAAGGTCTGGTGTCCTGGGGAACTTTCCCTTGCGGCCAACC
	CAATGACCCAGGAGTCTACACTCAAGTGTGCAAGTTCACCAAGTGGATAAATGACACCATGAAAAAG
	CATCGCTAACGCCACACTGAGTTAATTAACTGTGTGCTTCCAACAGAAATGCACAGGAGTGAGGAC
	GCCGATGACCTATGAAGTCAAATTTGACTTTACCTTTCCTCAAAGATATATTTAAACCTCATGCCCT
	GTTGATAAACCAATCAAATTGGTAAAGACCTAAAACCAAAACAAATAAAGAAACACAAAACCCTCAA
	ORF Start: ATG at 16		ORF Stop: TAA at 610
	SEQ ID NO:96	198 aa	MW at 21613.6 kD
NOV18c,	MARSLLLPLQILLLSLALETAGEEAQGDKIIDGAPCARGSHPWQVALLSGNQLHCGGVLVNERWVLT
CG145754-02
Protein Sequence	AAHCKMNEYTVHLGSDTLGDRRAQRIKASKSFRHPGYSTQTHVNDLKLISPQDCTKVYKDLLENSML
	CAGIPDSKKNACNGDSGGPLVCRGTLQGLVSWGTFPCGQPNDPGVYTQVCKFTKWINDTMKKHR
	SEQ ID NO:97	544 bp
NOV18d,	CACCGGATCCGAAGAAGCCCAGGGTGACAAGATTATTGATGGCGCCCCATGTGCAAGAGGCTCCCAC
252718128 DNA
Sequence	CCATGGCAGGTGGCCCTGCTCAGTGGCAATCAGCTCCACTGCGGAGGCGTCCTGGTCAATGAGCGCT
	GGGTGCTCACTGCCGCCCACTGCAAGATGAATGAGTACACCGTGCACCTGGGCAGTGATACGCTGGG
	CGACAGGAGAGCTCAGAGGATCAAGGCCTCGAAGTCATTCCGCCACCCCGGCTACTCCACACAGACC
	CATGTTAATGACCTCAAGCTCATCTCCCCCCAGGACTGCACGAAGGTTTACAAGGACTTACTGGAAA
	ATTCCATGCTGTGCGCTGGCATCCCCGACTCCAAGAAAAACGCCTGCAATGGTGACTCAGGGGGACC
	GTTGGTGTGCAGAGGTACCCTGCAAGGTCTGGTGTCCTGGGGAACTTTCCCTTGCGGCCAACCCAAT
	GACCCAGGAGTCTACACTCAAGTGTGCAAGTTCACCAAGTGGATAAATGACACCATGAAAAAGCATC
	TCGAGGGC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO:98	181 aa	MW at 19683.2 kD
NOV18d,	TGSEEAQGDKIIDGAPCARGSHPWQVALLSGNQLHCGGVLVNERWVLTAAHCKMNEYTVHLGSDTLG
252718128
Protein Sequence	DRRAQRIKASKSFRHPGYSTQTHVNDLKLISPQDCTKVYKDLLENSMLCAGIPDSKKNACNGDSGGP
	LVCRGTLQGLVSWGTFPCGQPNDPGVYTQVCKFTKWINDTMKKHLEG
	SEQ ID NO: 99	292 bp
NOV18e,	CACCGGATCCGAAGAAGCCCAGGGTGACAAGATTATTGATGGCGCCCCATGTGCAAGAGGCTCCCAC
252718152 DNA
Sequence	CCATGGCAGGTGGCCCTGCTCAGTGGCAATCAGCTCCACTGCGGAGGCGTCCTGGTCAATGAGCGCT
	GGGTGCTCACTGCCGCCCACTGCAAGATGAATGAGTACACCGTGCACCTGGGCAGTGATACGCTGGG
	CGACAGGAGAGCTCAGAGGATCAAGGCCTCGAAGTCATTCCGCCACCCCGGCTACTCCACACAGACC
	CATGTTAATGACCTCCTCGAGGGC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO: 100	97 aa	MW at 10551.7 kD
NOV18e,	TGSEEAQGDKIIDGAPCARGSHPWQVALLSGNQLHCGGVLVNERWVLTAAHCKMNEYTVHLGSDTLG
252718152
Protein Sequence	DRRAQRIKASKSFRHPGYSTQTHVNDLLEG
	SEQ ID NO: 101	742 bp
NOV18f,	AGGCTCCGCGGCCGCCCCCTTCACCGGATCCGCCAGGGGTGACAAGATTATTGATGGCGCCCCATGT
247856668 DNA
Sequence	GCAAGAGGCTCCCACCCATGGCAGGTGGCCCTGCTCAGTGGCAATCAGCTCCACTGCGGAGGCGTCC
	TGGTCAATGAGCGCTGGGTGCTCACTGCCGCCCACTGCAAGATGAATGAGTACACCGTGCACCTGGG
	CAGTGATACGCTGGGCGACAGGAGAGCTCAGAGGATCAAGGCCTCGAAGTCATTCCGCCACCCCGGC
	TACTCCACACAGACCCATGTTAATGACCTCATGCTCGTGAAGCTCAATAGCCAGGCCAGGCTGTCAT
	CCATGGTGAAGAAAGTCAGGCTGCCCTCCCGCTGCGAACCCCCTGGAACCACCTGTACTGTCTCCGG
	CTGGGGCACTACCACGAGCCCAGATGTGACCTTTCCCTCTGACCTCATGTGCGTGGATGTCAAGCTC
	ATCTCCCCCCAGGACTGCACGAAGGTTTACAAGGACTTACTGGAAAATTCCATGCTGTGCGCTGGCA
	TCCCCGACTCCAAGAAAAACGCCTGCAATGGTGACTCAGGGGGACCGTTGGTGTGCAGAGGTACCCT
	GCAAGGTCTGGTGTCCTGGGGAACTTTCCCTTGCGGCCAACCCAATGACCCAGGAGTCTACACTCAA
	GTGTGCAAGTTCACCAAGTGGATAAATGACACCATGAAAAAGCATCGCCTCGAGGGCAAGGGTGGGC
	GCGCC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO: 102	247 aa	MW at 26591.2 kD
NOV18f,	GSAAAPFTGSARGDKIIDGAPCARGSHPWQVALLSGNQLHCGGVLVNERWVLTAAHCKMNEYTVHLG
247856668
Protein Sequence	SDTLGDRRAQRIKASKSFRHPGYSTQTHVNDLMLVKLNSQARLSSMVKKVRLPSRCEPPGTTCTVSG
	WGTTTSPDVTFPSDLMCVDVKLISPQDCTKVYKDLLENSMLCAGIPDSKKNACNGDSGGPLVCRGTL
	QGLVSWGTFPCGQPNDPGVYTQVCKFTKWINDTMKKHRLEGKGGRA
	SEQ ID NO: 103	673 bp
NOV18g,	AGGCTCCGCGGCCGCCCCCTTCACCGGATCCGCCAGGGGTGACAAGATTATTGATGGCGCCCCATGT
247856705 DNA
Sequence	GCAAGAGGCTCCCACCCATGGCAGGTGGCCCTGCTCAGTGGCAATCAGCTCCACTGCGGAGGCGTCC
	TGGTCAATGAGCGCTGGGTGCTCACTGCCGCCCACTGCAAGATGAATGAGTACACCGTGCACCTGGG
	CAGTGATACGCTGGGCGACAGGAGAGCTCAGAGGATCAAGGCCTCGAAGTCATTCCGCCACCCCGGC
	TACTCCACACAGACCCATGTTAATGACCTCATGCTCGTGAAGCTCAATAGCCAGGCCAGGCTGTCAT
	CCATGGTGAAGAAAGTCAGGCTGCCCTCCCGCTGCGAACCCCCTGGAACCACCTGTACTGTCTCCGG
	CTGGGGCACTACCACGAGCCCAGATGTGACCTTTCCCTCTGACCTCATGTGCGTGGATGTCAAGCTC
	ATCTCCCCCCAGGACTGCACGAAGGTTTACAAGGACTTACTGGAAAATTCCATGCTGTGCGCTGGCA
	TCCCCGACTCCAAGAAAAACGCCTGCAATGGTGACTCAGGGGGACCGTTGGTGTGCAGAGGTACCCT
	GCAAGGTCTGGTGTCCTGGGGAACTTTCCCTTGCGGCCAACCCAATCTCGAGGGCAAGGGTGGGCGC
	GCC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO: 104	224 aa	MW at 23813.0 kD
NOV18g,	GSAAAPFTGSARGDKIIDGAPCARGSHPWQVALLSGNQLHCGGVLVNERWVLTAAHCKMNEYTVHLG
247856705
Protein Sequence	SDTLGDRRAQRIKASKSFRHPGYSTQTHVNDLMLVkLNSQARLSSMVKKVRLPSRCEPPGTTCTVSG
	WGTTTSPDVTFPSDLMCVDVKLISPQDCTKVYKDLLENSMLCAGIPDSKKNACNGDSGGPLVCRGTL
	QGLVSWGTFPCGQPNLEGKGGRA

[0444] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 18B.

TABLE 18B
Comparison of NOV18a against NOV18b through NOV18g.
	NOV18a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV18b	25 . . . 250	213/226 (94%)
	27 . . . 252	213/226 (94%)
NOV18c	16 . . . 250	176/235 (74%)
	19 . . . 198	177/235 (74%)
NOV18d	17 . . . 249	172/233 (73%)
	1 . . . 178	173/233 (73%)
NOV18e	17 . . . 111	92/95 (96%)
	1 . . . 95	93/95 (97%)
NOV18f	22 . . . 250	215/229 (93%)
	11 . . . 239	216/229 (93%)
NOV18g	22 . . . 230	193/209 (92%)
	11 . . . 219	194/209 (92%)

[0445] Further analysis of the NOV18a protein yielded the following properties shown in Table 18C.

TABLE 18C
Protein Sequence Properties NOV18a
PSort     0.6233 probability located in outside; 0.1000 probability
analysis: located in endoplasmic reticulum (membrane); 0.1000
          probability located in endoplasmic reticulum (lumen); 0.1000
          probability located in microbody (peroxisome)
SignalP   Cleavage site between residues 20 and 21
analysis:

[0446] 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 18D.

TABLE 18D
Geneseq Results for NOV18a
Geneseq	Protein/Organism/Length	NOV18a Residues/	Identities/Similarities	Expect
Identifier	[Patent #, Date]	Match Residues	for the Matched Region	Value
AAU82740	Amino acid sequence of	1 . . . 250	250/250 (100%)	e−150
	novel human protease #39 -	4 . . . 253	250/250 (100%)
	Homo sapiens, 253 aa.
	[WO200200860-A2,
	03-JAN-2002]
AAW05383	Human amyloid precursor	1 . . . 250	250/250 (100%)	e−150
	protein protease - Homo	4 . . . 253	250/250 (100%)
	sapiens, 253 aa.
	[WO9631122-A1,
	10-OCT-1996]
AAR67888	Human stratum corneum	1 . . . 250	250/250 (100%)	e−150
	chymotrophic recombinant	4 . . . 253	250/250 (100%)
	enzyme (SCCE) - Homo
	sapiens, 253 aa.
	[WO9500651-A,
	05-JAN-1995]
AAB21326	Human HSCEE - Homo	1 . . . 250	249/255 (97%)	e−146
	sapiens, 257 aa.	4 . . . 257	249/255 (97%)
	[WO200053776-A2,
	14-SEP-2000]
AAB98502	Human Stratum Corneum	26 . . . 250	225/225 (100%)	e−136
	Chymotryptic Enzyme,	1 . . . 225	225/225 (100%)
	SCCE, catalytic domain -
	Homo sapiens, 225 aa.
	[WO200129056-A1
	26-APR-2001]

[0447] 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 18E.

TABLE 18E
Public BLASTP Results for NOV18a
Protein
Accession		NOV18a Residues/	Identities/Similarities	Expect
Number	Protein/Organism/Length	Match Residues	for the Matched Portion	Value
P49862	Kallikrein 7 precursor (EC	1 . . . 250	250/250 (100%)	e−149
	3.4.21.-) (Stratum corneum	4 . . . 253	250/250 (100%)
	chymotryptic enzyme)
	(hSCCE) - Homo sapiens
	(Human), 253 aa.
AAH32005	Kallikrein 7 (chymotryptic,	1 . . . 250	249/250 (99%)	e−148
	stratum corneum) - Homo	4 . . . 253	249/250 (99%)
	sapiens (Human), 253 aa.
Q91VE3	Thymopsin (Stratum	3 . . . 250	185/248 (74%)	e−111
	corneum chymotryptic	5 . . . 249	212/248 (84%)
	enzyme) - Mus musculus
	(Mouse), 249 aa.
AAN03663	Kallikrein 7 short variant	70 . . . 250	181/181 (100%)	e−107
	protein - Homo sapiens	1 . . . 181	181/181 (100%)
	(Human), 181 aa.
Q9R048	Stratum corneum	3 . . . 235	175/233 (75%)	e−102
	chymotryptic enzyme - Mus	5 . . . 234	198/233 (84%)
	musculus (Mouse), 234 aa
	(fragment).

[0448] PFam analysis predicts that the NOV18a protein contains the domains shown in the Table 18F.

TABLE 18F
Domain Analysis of NOV18a
	NOV18a	Identities/Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
trypsin	27 . . . 242	93/262 (35%)	3.8e−87
		182/262 (69%)

Example 19

[0449] 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: 105	2028 bp
NOV19a,	TTGAGGACTTTATTATTATTTGGGTTCTTTTCATTTCTTCCCCTTCTGGGCAACGAAGCAATGAAAT
CG146279-01
DNA Sequence	TTCCAATCGAGACGCCAAGAAAACAGGTGAACTGGGATCCTAAAGTGGCCGTTCCCGCAGCAGCACC
	GGTGTGCCAGCCCAAGAGCGCCACTAACGGGCAACCCCCGGCTCCGGCTCCGACTCCAACTCCGCGC
	CTGTCCATTTCCTCCCGAGCCACAGTGGTAGCCAGGATGGAAGGCACCTCCCAAGGGGGCTTGCAGA
	CCGTCATGAAGTGGAAGACGGTGGTTGCCATCTTTGTGGTTGTGGTGGTCTACCTTGTCACTGGCGG
	TCTTGTCTTCCGGGCATTGGAGCAGCCCTTTGAGAGCAGCCAGAAGAATACCATCGCCTTGGAGAAG
	GCGGAATTCCTGCGGGATCATGTCTGTGTGAGCCCCCAGGAGCTGGAGACGTTGATCCAGCATGCTC
	TTGATGCTGACAATGCGGGAGTCAGTCCAATAGGAAACTCTTCCAACAACAGCAGCCACTGGGACCT
	CGGCAGTGCCTTTTTCTTTGCTGGAACTGTCATTACGACCATAGGGTATGGGAATATTGCTCCGAGC
	ACTGAAGGAGGCAAAATCTTTTGTATTTTATATGCCATCTTTGGAATTCCACTCTTTGGTTTCTTAT
	TGGCTGGAATTGGAGACCAACTTGGAACCATCTTTGGGAAAAGCATTGCAAGAGTGGAGAAGGTCTT
	TCGAAAAAAGCAAGTGAGTCAGACCAAGATCCGGGTCATCTCAACCATCCTGTTCATCTTGGCCGGC
	TGCATTGTGTTTGTGACGATCCCTGCTGTCATCTTTAAGTACATCGAGGGCTGGACGGCCTTGGAGT
	CCATTTACTTTGTGGTGGTCACTCTGACCACGGTGGGCTTTGGTGATTTTGTGGCAGGGGGAAACGC
	TGGCATCAATTATCGGGAGTGGTATAAGCCCCTAGTGTGGTTTTGGATCCTTGTTGGCCTTGCCTAC
	TTTGCAGCTGTCCTCAGTATGATCGGAGATTGGCTACGGGTTCTGTCCAAAAAGACAAAAGAAGAGG
	TGGGTGAAATCAAGGCCCATGCGGCAGAGTGGAAGGCCAATGTCACGGCTGAGTTCCGGGAGACACG
	GCGAAGGCTCAGCGTGGAGATCCACGATAAGCTGCAGCGGGCGGCCACCATCCGCAGCATGGAGCGC
	CGGCGGCTGGGCCTGGACCAGCGGGCCCACTCACTGGACATGCTGTCCCCCGAGAAGCGCTCTGTCT
	TTGCTGCCCTGGACACCGGCCGCTTCAAGGCCTCATCCCAGGAGAGCATCAACAACCGGCCCAACAA
	CCTGCGCCTGAAGGGGCCGGAGCAGCTGAACAAGCATGGGCAGGGTGCGTCCGAGGACAACATCATC
	AACAAGTTCGGGTCCACCTCCAGACTCACCAAGAGGAAAAACAAGGACCTCAAAAAGACCTTGCCCG
	AGGACGTTCAGAAAATCTACAAGACCTTCCGGAATTACTCCCTGGACGAGGAGAAGAAAGAGGAGGA
	GACGGAAAAGATGTGTAACTCAGACAACTCCAGCACAGCCATGCTGACGGACTGTATCCAGCAGCAC
	GCTGAGTTGGAGAACGGAATGATACCCACGGACACCAAAGACCGGGAGCCGGAGAACAACTCATTAC
	TTGAAGACAGAAACTAAATGTGAAGGACATTGGTCTTGGACTGAGCGTTGTGTGTGTGTGTGTGTGT
	GTTTTTAATATTCACACTGAGACATGTGCCTTAAACAGACTTTTTAGTCCAAAATTACATAGCATTG
	AAGAATATATTTCACTGTGCCATAAACAACTGAAAGCTTGCTCTGCCAAAAGGAATCAGAGAACAAG
	AACTTCATTTCAGATAGCAAACGCAGGACACACCAAGAGTGTCCGTGCACGTAGCCGGTTCTGGCCG
	TACATGTTAAGGGCATTTCAGTGGCAGTGCTGTACCCCTGGGCAGTGCTACCTGGGCACACACGTAG
	ACAAGGGCAGCTATTCCT
	ORF Start: ATG at 61		ORF Stop: TAA at 1690
	SEQ ID NO: 106	543 aa	MW at 60334.6 kD
NOV19a,	MKFPIETPRKQVNWDPKVAVPAAAPVCQPKSATNGQPPAPAPTPTPRLSISSRATVVARMEGTSQGG
CG146279-01
Protein Sequence	LQTVMKWKTVVAIFVVVVVYLVTGGLVFRALEQPFESSQKNTIALEKAEFLRDHVCVSPQELETLIQ
	HALDADNAGVSPIGNSSNNSSHWDLGSAFFFAGTVITTIGYGNIAPSTEGGKIFCILYAIFGIPLFG
	FLLAGIGDQLGTIFGKSIARVEKVFRKKQVSQTKIRVISTILFILAGCIVFVTIPAVIFKYIEGWTA
	LESIYFVVVTLTTVGFGDFVAGGNAGINYREWYKPLVWFWILVGLAYFAAVLSMIGDWLRVLSKKTK
	EEVGEIKAHAAEWKANVTAEFRETRRRLSVEIHDKLQRAATIRSMERRRLGLDQRAHSLDMLSPEKR
	SVFAALDTGRFKASSQESINNRPNNLRLKGPEQLNKHGQGASEDNIINKFGSTSRLTKRKNKDLKKT
	LPEDVQKIYKTFRNYSLDEEKKEEETEKMCNSDNSSTAMLTDCIQQHAELENGMIPTDTKDREPENN
	SLLEDRN

[0450] Further analysis of the NOVI9a protein yielded the following properties shown in Table 19B.

TABLE 19B
Protein Sequence Properties NOV19a
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:

[0451] 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
Geneseq	Protein/Organism/Length	NOV19a Residues/	Identities/Similarities	Expect
Identifier	[Patent #, Date]	Match Residues	for the Matched Region	Value
AAU81354	Novel human ion channel	1 . . . 543	543/543 (100%)	0.0
	protein #34 - Homo sapiens,	1 . . . 543	543/543 (100%)
	543 aa. [WO200185788-A2,
	15-NOV-2001]
AAU79472	Human novel transporter	1 . . . 543	543/543 (100%)	0.0
	protein - Homo sapiens, 543	1 . . . 543	543/543 (100%)
	aa. [WO200224748-A2,
	28-MAR-2002]
AAU79473	Human novel transporter	1 . . . 543	542/543 (99%)	0.0
	protein variant - Homo	1 . . . 543	543/543 (99%)
	sapiens, 543 aa.
	[WO200224748-A2,
		28-MAR-2002]
AAE16596	Human TWIK-Related K+	18 . . . 543	526/526 (100%)	0.0
	channel-2 (TREK-2) protein -	13 . . . 538	526/526 (100%)
	Homo sapiens, 538 aa.
	[WO200200715-A2,
	03-JAN-2002]
AAB47930	Human TREK2 - Homo	18 . . . 543	526/526 (100%)	0.0
	sapiens, 538 aa.	13 . . . 538	526/526 (100%)
	[WO200200715-A2,
	03-JAN-2002]

[0452] 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
Protein
Accession		NOV19a Residues/	Identities/Similarities	Expect
Number	Protein/Organism/Length	Match Residues	for the Matched Portion	Value
Q8TDK7	Potassium channel TREK2	1 . . . 543	542/543 (99%)	0.0
	splice variant b - Homo	1 . . . 543	542/543 (99%)
	sapiens (Human), 543 aa.
P57789	Potassium channel subfamily	18 . . . 543	526/526 (100%)	0.0
	K member 10 (Outward	13 . . . 538	526/526 (100%)
	rectifying potassium channel
	protein TREK-2) (TREK-2
	K+ channel subunit) - Homo
	sapiens (Human), 538 aa.
Q8TDK8	Potassium channel TREK2	18 . . . 543	525/526 (99%)	0.0
	splice variant a - Homo	18 . . . 543	525/526 (99%)
	sapiens (Human), 543 aa.
Q9JIS4	Potassium channel subfamily	1 . . . 543	520/544 (95%)	0.0
	K member 10 (Outward	1 . . . 538	529/544 (96%)
	rectifying potassium channel
	protein TREK-2) (TREK-2
	K+ channel subunit) - Rattus
	norvegicus (Rat), 538 aa.
P97438	Potassium channel subfamily	22 . . . 404	247/384 (64%)	e−136
	K member 2 (Outward	2 . . . 369	301/384 (78%)
	rectifying potassium channel
	protein TREK-1) (Two-pore
	potassium channel TPKC1)
	(TREK-1 K+channel
	subunit) - Mus musculus
	(Mouse), 411 aa.

[0453] PFam analysis predicts that the NOV 19a protein contains the domains shown in the Table 19E.

TABLE 19E
Domain Analysis of NOV19a
	NOV19a	Identities/Similarities	Expect
Pfam Domain	Match Region	for the Matched Region	Value
ion_trans	158 . . . 323	41/231 (18%)	0.046
		119/231 (52%)

[0454] 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: 107	2958 bp
NOV20a,	GCTCCTCCCCGCTGGCGGGGGGAGAAAGGGCAGGAGGCCTTCCGTCCCGGCTATAAAGGGCCCCGGA
CG146374-01
DNA Sequence	CCGCCGCGGCTCGCCTCGGCTTGCCTCGACACGCCTAGGCGCCCTCCGGCTCCGCCCTAGCCGCCGC
	GTCCCAGCTAGAGCTCCAGCGCCCGCTCAGGCCCCACTCGACCCTCTCGGGCCTCGGCTACTTGGAC
	TGCGGCGGAATATGGCGGCTCCGATGACTCCCGCGGCTCGGCCCGAGGACTACGAGGCGGCGCTCAA
	TGCCGCCCTGGCTGACGTGCCCGAACTGGCCAGACTCCTGGAGATCGACCCGTACTTGAAGCCCTAC
	GCCGTGGACTTCCAGCGCAGGTATAAGCAGTTTAGCCAAATTTTGAAGAACATTGGAGAAAATGAAG
	GTGGTATTGATAAGTTTTCCAGAGGCTATGAATCATTTGGCGTCCACAGATGTGCTGATGGTGGTTT
	ATACTGCAAAGAATGGGCCCCGGGAGCAGAAGGAGTTTTTCTTACTGGAGATTTTAATGGTTGGAAT
	CCATTTTCGTACCCATACAAAAAACTGGATTATGGAAAATGGGAGCTGTATATCCCACCAAAGCAGA
	ATAAATCTGTACTCGTGCCTCATGGATCCAAATTAAAGGTAGTTATTACTAGTAAAAGCGGAGAGAT
	CTTGTATCGTATTTCACCGTGGGCAAAGTATGTGGTTCGTGAAGGTGATAATGTGAATTATGATTGG
	ATACACTGGGATCCAGAACACTCATATGAGTTTAAGCATTCCAGACCAAAGAAGCCACGGAGTCTAA
	GAATTTATGAATCTCATGTGGGAATTTCTTCCCATGAAGGAAAAGTAGCTTCTTATAAACATTTTAC
	ATGCAATGTACTACCAAGAATCAAAGGCCTTGGATACAACTGCATTCAGTTGATGGCAATCATGGAG
	CATGCTTACTATGCCAGCTTTGGTTACCAAATCACAAGCTTCTTTGCAGCTTCCAGCCGTTATGGAT
	CACCTGAAGAGCTACAAGAACTGGTAGACACAGCTCATTCCATGGGTATCATAGTCCTCTTAGATGT
	GGTACACAGCCATGCTTCAAAAAATTCAGCAGATGGATTGAATATGTTTGATGGGACAGATTCCTGT
	TATTTTCATTCTGGACCTAGAGGGACTCATGATCTTTGGGATAGCAGATTGTTTGCCTACTCCAGGT
	TGAATATTTCAGACATCTAAGCCAATTAGAATCATGATTGTTTTGATTGCCAGAAATCCTTAAATCT
	GGGAAGTTTTAAGATTCCTTCTGTCAAACATAAGATGGTGGTTGGAAGAATATCGCTTTGATGGATT
	TCGTTTTGATGGTGTTACGTCCATGCTTTATCATCACCATGGAGTGGGTCAAGGTTTCTCAGGTGAT
	TACAGTGAATATTTCGGACTACAAGTAGATGAAGATGCCTTGACTTACCTCATGTTGGCAAATCATT
	TGGTTCACACGCTGTGTCCCGATTCTATAACAATAGCTGAGGATGTATCAGGAATGCCAGCTCTGTG
	CTCTCCAATTTCCCAGGGAGGGGGTGGTTTTGACTATCGACTAGCCATGGCAATTCCAGATAAGTGG
	ATTCAGCTACTTAAAGAGTTTAAAGATGAAGACTGGAACATGGGCGATATAGTATACACGCTCACAA
	ACAGGCGCTACCTTGAAAAGTGCATTGCTTATGCAGAGAGCCATGATCAGGCATTGGTTGGGGATAA
	GTCGCTGGCATTTTGGTTGATGGATGCCGAAATGTATACAAACATGAGTGTCCTGACTCCTTTTACT
	CCAGTTATTGATCGTGGAATACAGCTTCATAAAATGATTCGACTCATTACGCATGGGCTTGGTGGAG
	AAGGCTATCTCAATTTCATGGGTAATGAATTTGGGCATCCTGAATGGTTAGACTTCCCAAGAAAAGG
	AAATAATGAGAGTTACCATTATGCCAGGCGGCAGTTTCATTTAACTGACGACGACCTTCTTCGCTAC
	AAGTTCCTAAATAATTTTGACAGGGATATGAATAGATTGGAAGAAAGATATGGTTGGCTTGCAGCTC
	CACAGGCCTACGTGAGTGAAAAACATGAAGGCAATAAGATCATTGCTTTTGAAAGAGCAGGTCTTCT
	TTTCATTTTCAACTTCCATCCAAGCAAGAGCTACACTGACTACCGAGTTGGAACAGCATTGCCAGGG
	AAATTCAAAATTGTGCTAGATTCAGATGCAGCGGAATATGGAGGGCATCAGAGACTGGACCACAGCA
	CTGACTTTTTTTCTGAGGCTTTTGAACATAATGGGCGTCCCTATTCTCTTTTGGTGTACATTCCAAG
	CAGAGTGGCCCTCATCCTTCAGAATGTGGATCTGCCGAATTGAAGAGGCCTGATTTCAGCTCCACCA
	GATGCAGATTTGTGTTTTGTTTTCTTGTTATCACTGTCACACAGCTTATAACATGTATGCTTTTCAG
	AATACAGTTGTCTAGCCAAGCCATCAAGTGTCTGAAATTCAATATTGGTTTATGCAAATACAGCAAA
	CTTTTATTTAAGTAGATAGGAGAATATGTTTAAAATATTAGGAATCCTAGACCATATTTTCAAGTCA
	TCTTAGCAGCTAGGATTCTCAAATGGAAGTGTTATATATAATATGTTAAAAACATTTTGCTTTCCTG
	GCTAATTATTTGATCCTTTTAAATTCAAATTTGAATCATTTGTCATGTATGATTATTTCTGTTAAAT
	GTACACAGTATTTAAGATGGATATTTGGTGGCTCTATTTGTTCTGATATCTTTTGGTCTAAATTATG
	AGGTACCAAGATTGTTTCTTTGTTTCTTTTTTTCAAATTGTGTTTAGAAATACTGTAATAAATATGC
	AGTAGTGATATAAAGAATTATATCCAAGGTAATATAAAAGCCATTACGTATGAACTCAAAAAAAAAA
	AAAAAAAAAA
	ORF Start: ATG at 213		ORF Stop: TAA at 1224
	SEQ ID NO: 108	337 aa	MW at 38247.8 kD
NOV20a,	MAAPMTPAARPEDYEAALNAALADVPELARLLEIDPYLKPYAVDFQRRYKQFSQILKNIGENEGGID
CG146374-01
Protein Sequence	KFSRGYESFGVHRCADGGLYCKEWAPGAEGVFLTGDFNGWNPFSYPYKKLDYGKWELYIPPKQNKSV
	LVPHGSKLKVVITSKSGEILYRISPWAKYVVREGDNVNYDWIHWDPEHSYEFKHSRPKKPRSLRIYE
	SHVGISSHEGKVASYKHFTCNVLPRIKGLGYNCIQLMAIMEHAYYASFGYQITSFFAASSRYGSPEE
	LQELVDTAHSMGIIVLLDVVHSHASKNSADGLNMFDGTDSCYFHSGPRGTHDLWDSRLFAYSRLNIS
	DI

[0455] Further analysis of the NOV20a protein yielded the following properties shown in Table 20B.

TABLE 20B
Protein Sequence Properties NOV20a
PSort     0.7480 probability located in microbody (peroxisome); 0.6000
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:

[0456] 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
Geneseq	Protein/Organism/Length	NOV20a Residues/	Identities/Similarities	Expect
Identifier	[Patent #, Date]	Match Residues	for the Matched Region	Value
AAB90803	Human shear stress-response	1 . . . 330	328/330 (99%)	0.0
	protein SEQ ID NO: 106 -	1 . . . 330	329/330 (99%)
	Homo sapiens, 702 aa.
	[WO200125427-A1,
	12-APR-2001]
ABB60350	Drosophila melanogaster	22 . . . 329	170/314 (54%)	e−102
	polypeptide SEQ ID NO	1 . . . 314	227/314 (72%)
	7842 - Drosophila
	melanogaster, 865 aa.
	[WO200171042-A2,
	27-SEP-2001]
AAB49603	Glycogen branching enzyme	31 . . . 329	175/305 (57%)	1e−98
	amino acid sequence -	12 . . . 314	228/305 (74%)
	Aspergillus nidulans, 686 aa.
	[JP2000279180-A,
	10-OCT-2000]
AAG39093	Arabidopsis thaliana protein	30 . . . 329	161/302 (53%)	3e−92
	fragment SEQ ID NO: 48322	22 . . . 321	214/302 (70%)
	- Arabidopsis thaliana, 721
	aa. [EP1033405-A2,
	06-SEP-2000]
AAG39092	Arabidopsis thaliana protein	30 . . . 329	161/302 (53%)	3e−92
	fragment SEQ ID NO: 48321	159 . . . 458	214/302 (70%)
	- Arabidopsis thaliana, 858
	aa. [EP1033405-A2,
	06-SEP-2000]

[0457] 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
Protein
Accession		NOV20a Residues/	Identities/Similarities	Expect
Number	Protein/Organism/Length	Match Residues	for the Matched Portion	Value
Q96EN0	Similar to glucan	1 . . . 330	330/330 (100%)	0.0
	(1,4-alpha-), branching	1 . . . 330	330/330 (100%)
	enzyme 1 (glycogen
	branching enzyme, Andersen
	disease, glycogen storage
	disease type IV) - Homo
	sapiens (Human), 702 aa.
Q04446	1,4-alpha-glucan branching	1 . . . 330	328/330 (99%)	0.0
	enzyme (EC 2.4.1.18)	1 . . . 330	329/330 (99%)
	(Glycogen branching
	enzyme) (Brancher enzyme)
	- Homo sapiens (Human),
	702 aa.
Q9D6Y9	2310045H19Rik protein	1 . . . 330	291/330 (88%)	e−179
	(RIKEN cDNA 2310045H19	1 . . . 330	310/330 (93%)
	gene) - Mus musculus
	(Mouse), 702 aa.
AAF58416	CG4023-PA - Drosophila	22 . . . 329	170/314 (54%)	e−102
	melanogaster (Fruit fly), 685	1 . . . 314	227/314 (72%)
	aa.
Q9V6K7	GG4023 protein - Drosophila	22 . . . 329	170/314 (54%)	e−102
	melanogaster (Fruit fly), 865	1 . . . 314	227/314 (72%)
	aa.

[0458] PFam analysis predicts that the NOV20a protein contains the domains shown in the Table 20E.

TABLE 20E
Domain Analysis of NOV20a
		Identities/
		Similarities
	NOV20a	for the Matched
Pfam Domain	Match Region	Region	Expect Value
isoamylase_N	73 . . . 168	31/123(25%)	5.1e−11
		64/123 (52%)

Example 21

[0459] 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: 109	885 bp
NOV21a.	TGGATGCTGGCGGTCCTCTACCTGGTCTGGCTCTATTGGGATAGAAACATACCCAGGGCTGGTGGAA
CG146403-01
DNA Sequence	GGCGTTCGGAGTGGATAAGGAACCGGGCAATTTGGAGACAACTAAGGGATTATTATCCTGTCAAGCT
	GGTGAAAACAGCAGAGCTGCCCCCGGATCGGAACTACGTGCTGGGCGCCCACCCTCATGGGATCATG
	TGTACAGGCTTCCTCTGTAATTTCTCCACCGAGAGCAATGGCTTCTCCCAGCTCTTCCCGGGGCTCC
	GGCCCTGGTTAGCCGTGCTGGCTGGCCTCTTCTACCTCCCGGTCTATCGCGACTACATCATGTCCTT
	TGGTCTCTGTCCGGTGAGCCGCCAGAGCCTGGACTTCATCCTGTCCCAGCCCCAGCTCGGGCAGGCC
	GTGGTCATCATGGTGGGGGGTGCGCACGAGGCCCTGTATTCAGTCCCCGGGGAGCACTGCCTTACGC
	TCCAGAAGCGCAAAGGCTTCGTGCGCCTGGCGCTGAGGCACGGGGCGTCCCTGGTGCCCGTGTACTC
	CTTTGGGGAGAATGACATCTTTAGACTTAAGGCTTTTGCCACAGGCTCCTGGCAGCATTGGTGCCAG
	CTCACCTTCAAGAAGCTCATGGGCTTCTCTCCTTGCATCTTCTGGGGTCGCGGTCTCTTCTCAGCCA
	CCTCCTGGGGCCTGCTGCCCTTTGCTGTGCCCATCACCACTGTGGGTGAGCCCATCCCCGTCCCCCA
	GCGCCTCCACCCCACCGAGGAGGAAGTCAATCACTATCACGCCCTCTACATGACGGCCCTGGAGCAG
	CTCTTCGAGGAGCACAAGGAAAGCTGTGGGGTCCCCGCTTCCACCTGCCTCACCTTCATCTAGGCCT
	GGCCGCGGCCTTTC
	ORF Start: ATG at 4		ORF Stop: TAG at 865
	SEQ ID NO: 110	287 aa	MW at 32641.7 kD
NOV21a,	MLAVLYLVWLYWDRNIPRAGGRRSEWIRNRAIWRQLRDYYPVKLVKTAELPPDRNYVLGAHPHGIMC
CG146403-01
Protein Sequence	TGFLCNFSTESNGFSQLFPGLRPWLAVLAGLFYLPVYRDYIMSFGLCPVSRQSLDFILSQPQLGQAV
	VIMVGGAHEALYSVPGEHCLTLQKRKGFVRLALRHGASLVPVYSFGENDIFRLKAFATGSWQHWCQL
	TFKKLMGFSPCIFWGRGLFSATSWGLLPFAVPITTVGEPIPVPQRLHPTEEEVNHYHALYMTALEQL
	FEEHKESCGVPASTCLTFI

[0460] Further analysis of the NOV21a protein yielded the following properties shown in Table 21B.

TABLE 21B
Protein Sequence Properties NOV21a
PSort analysis:   0.5500 probability located in endoplasmic
                  reticulum (membrane); 0.3814 probability
                  located in lysosome (lumen); 0.3200 probability
                  located in microbody (peroxisome); 0.1000 probability
                  located in endoplasmic reticulum (lumen)
SignalP analysis: Cleavage site between residues 22 and 23

[0461] A search of the NOV21a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 21C.

TABLE 21C
Geneseq Results for NOV21a
		NOV21a
		Residues/	Identities/
Geneseq	Protein/Organism/Length	Match	Similarities for the	Expect
Identifier	[Patent #, Date]	Residues	Matched Region	Value
AAM80262	Human protein SEQ ID NO	43 . . . 237	195/195 (100%)	e−115
	3908 - Homo sapiens, 223	29 . . . 223	195/195 (100%)
	aa. [WO200157190-A2,
	09-AUG-2001]
ABB75677	Breast protein-eukaryotic	l . . . 284	158/285 (55%)	1e−97
	conserved gene 1	101 . . . 385	218/285 (76%)
	(BSTP-ECG1) protein -
	Homo sapiens, 388 aa.
	[WO200208260-A2,
	31-JAN-2002]
AAB66170	Protein of the invention #82 -	1 . . . 284	158/285 (55%)	1e−97
	Unidentified, 388 aa.	101 . . . 385	218/285 (76%)
	[WO200078961-A1,
	28-DEC-2000]
AAU29191	Human PRO polypeptide	1 . . . 284	158/285 (55%)	1e−97
	sequence #168 - Homo	101 . . . 385	218/285 (76%)
	sapiens, 388 aa.
	[WO200168848-A2,
	20-SEP-2001]
AAY99421	Human PR01433 (UNQ738)	1 . . . 284	158/285 (55%)	1e−97
	amino acid sequence SEQ ID	101 . . . 385	218/285 (76%)
	NO: 292 - Homo sapiens, 388
	aa. [WO200012708-A2,
	09-MAR-2000]

[0462] 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
Q9UDW7	WUGSC: H_DJ0747G18.5	43 . . . 287	244/246 (99%)	e−145
	protein - Homo sapiens	16 . . . 261	244/246 (99%)
	(Human), 261 aa (fragment).
CAD38961	Hypothetical protein - Homo	1 . . . 284	158/285 (55%)	3e−97
	sapiens (Human), 434 aa	147 . . . 431	218/285 (76%)
	(fragment).
Q96PD7	Diacyiglycerol	1 . . . 284	158/285 (55%)	3e−97
	acyltransferase 2	1O1 . . . 385	218/285 (76%)
	(Hypothetical 43.8 kDa
	protein) - Homo sapiens
	(Human), 388 aa.
Q9BYE5	GSl999full protein - Homo	1 . . . 284	158/285 (55%)	3e−97
	sapiens (Human), 297 aa.	1O . . . 294	218/285 (76%)
Q9DCV3	0610010B06Rik protein	1 . . . 284	159/285 (55%)	8e−97
	(Diacyiglycerol acyltransferase	101 . . . 385	217/285 (75%)
	2) - Mus
	musculus (Mouse), 388 aa.

Example 22

[0463] 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: 111	1135 bp
NOV22a,	CACAGTAAGAGATTATAGCAAAGCATCTATAATCAACTCAGCTTAAGAAGTTTTGACCTTCTGGTTA
CG146513-01
DNA Sequence	GGCTTCTTGCCACAACAGAACAGCACCATAACCATGGCTTTCTTCTCCCGACTGAATCTCCAGGAGG
	GCCTCCAAACCTTCTTTGTTTTGCAATGGATCCCAGTCTATATATTTTTAGGAGCTATTCCCATTCT
	CCTTATACCCTACTTTCTGTTATTCAGTAAGTTCTGGCCCTTGGCTGTGCTCTCCTTAGCCTGGCTC
	ACCTATGATTGGAACACCCACAGTCAAGGTGGCAGGCGTTCAGCTTGGGTACGAAACTGGACCCTAT
	GGAAGTATTTCCGAAATTACTTCCCAGTACAGCTGGTGAAGACTCATGATCTTTCTCCCAAACACAA
	CTACATCATTGCCAATCACCCCCATGGCATTCTCTCTTTTGGTGTCTTCATCAACTTTGCCACTGAG
	GCCACTGGCATTGCTCGGATTTTCCCATCCATCACTCCCTTTGTAGGGACCTTAGAAAGGATATTTT
	GGATCCCAATTGTGCGAGAATATGTGATGTCAATGGGTGTGTGCCCTGTGAGTAGCTCAGCCTTGAA
	GTACTTGCTGACCCAGAAAGGCTCAGGCAATGCCGTGGTTATTGTGGTGGGTGGAGCTGCTGAAGCT
	CTCTTGTGCCGACCAGGAGCCTCCACTCTCTTCCTCAAGCAGCGTAAAGGTTTTGTGAAGATGGCAC
	TGCAAACAGGGGCATACCTTGTCCCTTCATATTCCTTTGGTGAGAACGAAGTTTTCAATCAGGAGAC
	CTTCCCTGAGGGCACGTGGTTAAGGTTGTTCCAAAAAACCTTCCAGGACACATTCAAAAAAATCCTG
	GGACTAAATTTCTGTACCTTCCATGGCCGGGGCTTCACTCGCGGATCCTGGGGCTTCCTGCCTTTCA
	ATCGGCCCATTACCACTGTTGGGGAACCCCTTCCAATTCCCAGGATTAAGAGGCCAAACCAGAAGAC
	AGTAGACAAGTATCACGCACTCTACATCAGTGCCCTGCGCAAGCTCTTTGACCAACACAAAGTTGAA
	TATGGCCTCCCTGAGACCCAAGAGCTGACAATTACATAACAGGAGCCACATTCCCCATTGATC
	ORF Start: ATG at 101		ORF Stop: TAA at 1109
	SEQ ID NO: 112	336 aa	MW at 38493.6 kD
NOV22a,	MAFFSRLNLQEGLQTFFVLQWIPVYIFLGAIPILLIPYFLLFSKFWPLAVLSLAWLTYDWNTHSQGG
CG146513-01
Protein Sequence	RRSAWVRNWTLWKYFRNYFPVQLVKTHDLSPKHNYIIANHPHGILSFGVFINFATEATGIARIFPSI
	TPFVGTLERIFWIPIVREYVMSMGVCPVSSSALKYLLTQKGSGNAVVIVVGGAAEALLCRPGASTLF
	LKQRKGFVKMALQTGAYLVPSYSFGENEVFNQETFPEGTWLRLFQKTFQDTFKKILGLNFCTFHGRG
	FTRGSWGFLPFNRPITTVGEPLPIPRIKRPNQKTVDKYHALYISALRKLFDQHKVEYGLPETQELTI
	T

[0464] Further analysis of the NOV22a protein yielded the following properties shown in Table 22B.

TABLE 22B
Protein Sequence Properties NOV22a
PSort analysis:   0.6850 probability located in plasma membrane;
                  0.6400 probability located in endoplasmic reticulum
                  (membrane); 0.3880 probability located in microbody
                  (peroxisome); 0.3700 probability located in Golgi body
SignalP analysis: Cleavage site between residues 65 and 66

[0465] A search of the NOV22a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 22C.

TABLE 22C
Geneseq Results for NOV22a
		NOV22a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAM06866	Human foetal protein, SEQ	1 . . . 216	211/216 (97%)	e−124
	ID NO: 1074 - Homo	1 . . . 216	214/216 (98%)
	sapiens, 225 aa.
	[WO200155339-A2,
	02-AUG-2001]
ABB75677	Breast protein-eukaryotic	1 . . . 335	171/337 (50%)	e−101
	conserved gene 1	56 . . . 387	237/337 (69%)
	(BSTP-ECG1) protein -
	Homo sapiens, 388 aa.
	[WO200208260-A2,
	31-JAN-2002]
AAB66170	Protein of the invention #82 -	1 . . . 335	171/337 (50%)	e−101
	Unidentified, 388 aa.	56 . . . 387	237/337 (69%)
	[WO200078961-A1,
	28-DEC-2000]
AAU29191	Human PRO polypeptide	1 . . . 335	171/337 (50%)	e−101
	sequence #168 - Homo	56 . . . 387	237/337 (69%)
	sapiens, 388 aa.
	[WO200168848-A2,
	20-SEP-2001]
AAY99421	Human PR01433 (UNQ738)	1 . . . 335	171/337 (50%)	e−101
	amino acid sequence SEQ ID	56 . . . 387	237/337 (69%)
	NO: 292 - Homo sapiens, 388
	aa. [WO200012708-A2,
	09-MAR-2000]

[0466] In a BLAST search of public sequence datbases, the NOV22a protein was found to have homology to the proteins shown in the BLASTP data in Table 22D.

TABLE 22D
Public BLASTP Results for NOV22a
		NOV22a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9DCV3	0610010B06Rik protein	1 . . . 335	172/337(51%)	e−101
	(Diacyiglycerol	56 . . . 387	238/337 (70%)
	acyltransferase 2) - Mus
	musculus (Mouse), 388 aa.
CAD38961	Hypothetical protein - Homo	1 . . . 335	171/337 (50%)	e−100
	sapiens (Human), 434 aa	102 . . . 433	237/337 (69%)
	(fragment).
Q96PD7	Diacyiglycerol	1 . . . 335	171/337 (50%)	e−100
	acyltransferase 2	56 . . . 387	237/337 (69%)
	(Hypothetical 43.8 kDa
	protein) - Homo sapiens
	(Human), 388 aa.
Q8TAB1	BA351K23.5 (Novel protein) -	38 . . . 335	161/299 (53%)	2e−98
	Homo sapiens (Human),	1 . . . 295	221/299 (73%)
	296 aa (fragment).
Q9BYE5	GS1999full protein - Homo	39 . . . 335	161/299 (53%)	4e−96
	sapiens (Human), 297 aa.	2 . . . 296	217/299 (71%)

Example 23

[0467] 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: 113	1022 bp
NOV23a,	ACTGTTCTGAGATCTTTGCCTCCCTCAGGCTCCCGAGAATCATGGCTCATTCCAAGCAGCCTAGTCA
CG146522-01
DNA Sequence	CTTCCAGAGTCTGATGCTTCTGCAGTGGCCTTTGAGCTACCTTGCCATCTTGTTCGTCTACCTGCTG
	TTTACATCCTTGTGGCCGCTACCAGTGCTTTACTTTGCCTGGTTGTTCCTGGACTGGAAGACCCCAG
	AGCGAGGTGGCAGGCGTTCGGCCTGGGTAAGGAACTGGTGTGTCTGGACCCACATCAGGGACTATTT
	CCCCATTATCCTGAAGACAAAGGACCTATCACCTGAGCACAACTACCTCATGGGGGTTCACCCCCAT
	GGCCTCCTGACCTTTGGCGCCTTCTGCAACTTCTGCACTGAGGCCACAGGCTTCTCGAAGACCTTCC
	CAGGCATCACTCCTCACTTGGCCACGCTGTCCTGGTTCTTCAAGATCCCCTTTGTTAGGGAGTACCT
	CATGGCCAAAGGTGTGTGCTCTGTGAGCCAGCCAGCCATCAACTATCTGCTGAGCCATGGCACTGGC
	AACCTCGTGGGCATTGTAGTGGGAGGTGTGGGTGAGGCCCTGCAAAGTGTGCCCAACACCACCACCC
	TCATCCTCCAGAAGCGCAAGGGGTTCGTGCGCACAGCCCTCCAGCATGGGGCTCATCTGGTCCCCAC
	CTTCACTTTTGGGGAAACTGAGGTGTATGATCAGGTGCTGTTCCATAAGGATAGCAGGATGTACAAG
	TTCCAGAGCTGCTTCCGCCGTATCTTTGGTTTCTACTGTTGTGTCTTCTATGGACAAAGCTTCTGTC
	AAGGCTCCACTGGGCTCCTGCCATACTCCAGGCCTATTGTCACTGTTGGGGAGCCTCTGCCACTGCC
	CCAAATTGAAAAGCCAAGCCAGGAGATGGTGGACAAATACCATGCACTTTATATGGATGCTCTGCAC
	AAACTGTTCGACCAGCATAAGACCCACTATGGCTGCTCAGAGACCCAAAAGCTGTTTTTCCTGTGAA
	TGAAGGTACTGCATGCC
	ORF Start: ATG at 42		ORF Stop: TGA at 1002
	SEQ ID NO: 114	320 aa	MW at 36773.5 kD
NOV23a,	MAHSKQPSHFQSLMLLQWPLSYLAILFVYLLFTSLWPLPVLYFAWLFLDWKTPERGGRRSAWVRNWC
CG146522-01
Protein Sequence	VWTHIRDYFPIILKTKDLSPEHNYLMGVHPHGLLTFGAFCNFCTEATGFSKTFPGITPHLATLSWFF
	KIPFVREYLMAKGVCSVSQPAINYLLSHGTGNLVGIVVGGVGEALQSVPNTTTLILQKRKGFVRTAL
	QHGAHLVPTFTFGETEVYDQVLFHKDSRMYKFQSCFRRIFGFYCCVFYGQSFCQGSTGLLPYSRPIV
	TVGEPLPLPQIEKPSQEMVDKYHALYMDALHKLFDQHKTHYGCSETQKLFFL

[0468] Further analysis of the NOV23a protein yielded the following properties shown in Table 23B.

TABLE 23B
Protein Sequence Properties NOV23a
PSort analysis:   0.7284 probability located in outside; 0.3880
                  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 43 and 44

[0469] A search of the NOV23a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 23C.

TABLE 23C
Geneseq Results for NOV23a
		NOV23a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
ABB75677	Breast protein-eukaryotic	4 . . . 317	165/324 (50%)	1e−93
	conserved gene 1	62 . . . 385	224/324 (68%)
	(BSTP-ECG1) protein -
	Homo sapiens, 388 aa.
	[WO200208260-A2,
	31-JAN-2002]
AAB66170	Protein of the invention #82 -	4 . . . 317	165/324 (50%)	1e−93
	Unidentified, 388 aa.	62 . . . 385	224/324 (68%)
	[WO200078961-A1,
	28-DEC-2000]
AAU29191	Human PRO polypeptide	4 . . . 317	165/324 (50%)	1e−93
	sequence #168 - Homo	62 . . . 385	224/324 (68%)
	sapiens, 388 aa.
	[WO200168848-A2,
	20-SEP-2001]
AAY99421	Human PR01433 (UNQ738)	4 . . . 317	165/324 (50%)	1e−93
	amino acid sequence SEQ ID	62 . . . 385	224/324 (68%)
	NO: 292 - Homo sapiens, 388
	aa. [WO200012708-A2,
	09-MAR-2000]
AAY94889	Human protein clone	11 . . . 319	144/318 (45%)	3e−74
	HP02485 - Homo sapiens, 334 aa.	16 . . . 333	200/318 (62%)
	[WO200005367-A2,
	03-FEB-2000]

[0470] In a BLAST search of public sequence datbases, the NOV23a protein was found to have homology to the proteins shown in the BLASTP data in Table 23D.

TABLE 23D
Public BLASTP Results for NOV23a
		NOV23a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q8TAB1	BA351K23.5 (Novel protein) -	30 . . . 317	163/291 (56%)	5e−96
	Homo sapiens (Human),	3 . . . 293	214/291 (73%)
	296 aa (fragment).
Q9DCV3	0610010B06Rik protein	4 . . . 317	166/324 (51%)	2e−93
	(Diacyiglycerol	62 . . . 385	225/324 (69%)
	acyltransferase 2) - Mus
	musculus (Mouse), 388 aa.
CAD38961	Hypothetical protein - Homo	4 . . . 317	165/324 (50%)	3e−93
	sapiens (Human), 434 aa	108 . . . 431	224/324 (68%)
	(fragment).
Q96PD7	Diacyiglycerol	4 . . . 317	165/324 (50%)	3e−93
	acyltransferase 2	62 . . . 385	224/324 (68%)
	(Hypothetical 43.8 kDa
	protein) - Homo sapiens
	(Human), 388 aa.
Q9BYE5	GS1999full protein - Homo	28 . . . 317	156/294 (53%)	1e−89
	sapiens (Human), 297 aa.	1 . . . 294	210/294 (71%)

Example 24

[0471] 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: 115	1056 bp
NOV24a,	CATTTTCCAAAGGTGTCACAGGAAGAGCATGGCAGAGCTGGGACTGGGAGCCAGGTCACCATGGCTT
CG146531-01
DNA Sequence	TCTTCTCCCGACTGAATCTCCAGGAGGGCCTCCAAACCTTCTTTGTTTTGCAATGGATCCCAGTCTA
	TATATTTTTAGGTTTGTTCGTCTACCTGCTGTTTACATCCTTGTGGCCGCTACCAGTGCTTTACTTT
	GCCTGGTTGTTCCTGGACTGGAAGACCCCAGAGCGAGGTGGCAGGCGTTCGGCCTGGGTAAGGAACT
	GGTGTGTCTGGACCCACATCAGGGACTATTTCCCCATTCAGATCCTGAAGACAAAGGACCTATCACC
	TGAGCACAACTACCTCATGGGGGTTCACCCCCATGGCCTCCTGACCTTTGGCGCCTTCTGCAACTTC
	TGCACTGAGGCCACAGGCTTCTCGAAGACCTTCCCAGGCATCACTCCTCACTTGGCCACGCTGTCCT
	GGTTCTTCAAGATCCCCTTTGTTAGGGAGTACCTCATGGCCAAAGGTGTGTGCTCTGTGAGCCAGCC
	AGCCATCAACTATCTGCTGAGCCATGGCACTGGCAACCTCGTGGGCATTGTAGTGGGAGGTGTGGGT
	GAGGCCCTGCAAAGTGTGCCCAACACCACCACCCTCATCCTCCAGAAGCGCAAGGGGTTCGTGCGCA
	CAGCCCTCCAGCATGGGGCTCATCTGGTCCCCACCTTCACTTTTGGGGAAACTGAGGTGTATGATCA
	GGTGCTGTTCCATAAGGATAGCAGGATGTACAAGTTCCAGAGCTGCTTCCGCCGTATCTTTGGTTTC
	TACTGTTGTGTCTTCTATGGACAAAGCTTCTGTCAAGGCTCCACTGGGCTCCTGCCATACTCCAGGC
	CTATTGTCACTGTTGGGGAGCCTCTGCCACTGCCCCAAATTGAAAAGCCAAGCCAGGAGATGGTGGA
	CAAATACCATGCACTTTATATGGATGCTCTGCACAAACTGTTCGACCAGCATAAGACCCACTATGGC
	TGCTCAGAGACCCAAAAGCTGTTTTTCCTGTGAATGAAGGTACTGCATCCC
	ORF Start: ATG at 61		ORF Stop: TGA at 1036
	SEQ ID NO: 116	325 aa	MW at 37453.3 kD
NOV24a,	MAFFSRLNLQEGLQTFFVLQWIPVYIFLGLFVYLLFTSLWPLPVLYFAWLFLDWKTPERGGRRSAWV
CG146531-01
Protein Sequence	RNWCVWTHIRDYFPIQILKTKDLSPEHNYLMGVHPHGLLTFGAFCNFCTEATGFSKTFPGITPHLAT
	LSWFFKIPFVREYLMAKGVCSVSQPAINYLLSHGTGNLVGIVVGGVGEALQSVPNTTTLILQKRKGF
	VRTALQHGAHLVPTFTFGETEVYDQVLFHKDSRMYKFQSCFRRIFGFYCCVFYGQSFCQGSTGLLPY
	SRPIVTVGEPLPLPQIEKPSQEMVDKYHALYMDALHKLFDQHKTHYGCSETQKLFFL

[0472] Further analysis of the NOV24a protein yielded the following properties shown in Table 24B.

TABLE 24B
Protein Sequence Properties NOV24a
PSort analysis:   0.8200 probability located in outside;
                  0.3880 probability located in microbody
                  (peroxisome); 0.1000 probability located in
                  endoplasmic reticulum (membrane); 0.1000
                  probability located in endoplasinic reticulum (lumen)
SignalP analysis: Cleavage site between residues 47 and 48

[0473] 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 24C.

Table 24C
Geneseq Results for NOV24a
		NOV24a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
ABB75677	Breast protein-eukaryotic	1 . . . 322	166/330 (50%)	2e−96
	conserved gene 1	56 . . . 385	230/330 (69%)
	BSTP-ECG1) protein -
	Homo sapiens, 388 aa.
	[WO200208260-A2,
	31-JAN-2002]
AAB66170	Protein of the invention #82 -	1 . . . 322	166/330 (50%)	2e−96
	Unidentified, 388 aa.	56 . . . 385	230/330 (69%)
	[WO200078961-A1,
	28-DEC-2000]
AAU29191	Human PRO polypeptide	1 . . . 322	166/330 (50%)	2e−96
	sequence #168 - Homo	56 . . . 385	230/330 (69%)
	sapiens, 388 aa.
	[WO200168848-A2,
	20-SEP-2001]
AAY99421	Human PRO 1433 (UNQ738)	1 . . . 322	166/330 (50%)	2e−96
	amino acid sequence SEQ ID	56 . . . 385	230/330 (69%)
	NO: 292 - Homo sapiens, 388
	aa. [WO200012708-A2,
	09-MAR-2000]
AAY94889	Human protein clone	13 . . . 324	147/321 (45%)	2e−75
	HP02485 - Homo sapiens, 334 aa.	15 . . . 333	200/321 (61%)
	[WO200005367-A2,
	03-FEB-2000]

[0474] 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 24D.

TABLE 24D
Public BLASTP Results for NOV24a
		NOV24a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q8TAB1	BA351K23.5 (Novel protein) -	34 . . . 322	163/291 (56%)	1e−97
	Homo sapiens (Human),	3 . . . 293	215/291 (73%)
	296 aa (fragment).
CAD38961	Hypothetical protein - Homo	1 . . . 322	166/330 (50%)	6e−96
	sapiens (Human), 434 aa	102 . . . 431	230/330 (69%)
	(fragment).
Q9DCV3	0610010B06Rik protein	1 . . . 322	167/330 (50%)	6e−96
	(Diacylglycerol	56 . . . 385	230/330 (69%)
	acyltransferase 2) - Mus
	musculus (Mouse), 388 aa.
Q96PD7	Diacyiglycerol	1 . . . 322	166/330 (50%)	6e−96
	acyltransferase 2	56 . . . 385	230/330 (69%)
	(Hypothetical 43.8 kDa
	protein) - Homo sapiens
	(Human), 388 aa.
Q9BYE5	GS1999full protein - Homo	32 . . . 322	157/294 (53%)	1e−91
	sapiens (Human), 297 aa.	1 . . . 294	211/294 (71%)

Example 25

[0475] 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: 117	951 bp
NOV25a,	ATGGGGCTTCGGGCAGGCCCCATCCTGCTTCTGCTGCTGTGGCTGCTGCCAGGGGCCCATTGGGATG
CG147274-01
DNA Sequence	TGCTGCCTTCAGAATGCGGCCACTCCAAGGAGGCCGGGAGGATTGTGGGAGGCCAAGACACCCAGGA
	AGGACGCTGGCCGTGGCAGGTTGGCCTGTGGTTGACCTCAGTGGGGCATGTATGTGGGGGCTCCCTC
	ATCCACCCACGCTGGGTGCTCACAGCCGCCCACTGCTTCCTGAGGTCTGAGGATCCCGGGCTCTACC
	ATGTTAAAGTCGGAGGGCTGACACCCTCACTTTCAGAGCCCCACTCGGCCTTGGTGGCTGTGAGGAG
	GCTCCTGGTCCACTCCTCATACCATGGGACCACCACCAGCGGGGACATTGCCCTGATGGAGCTGGAC
	TCCCCCTTGCAGGCCTCCCAGTTCAGCCCCATCTGCCTCCCAGGACCCCAGACCCCCCTCGCCATTG
	GGACCGTGTGCTGGGTAAACGGGCTGGGGCCCACATCACATCCAGCCCTGGCGAGTGTCCTTCAGGA
	GGTGGCTGTGCCCCTCCTGGACTCGAACATGTGTGAGCTGATGTACCACCTAGGAGAGCCCAGCCTG
	GCTGGCCAGCGCCTCATCCAGGACGACATGCTCTGTGCTGGCTCTGTCCAGGGCAAGAAAGACTCCT
	GCCAGGGTGACTCCGGGGGGCCGCTGGTCTGCCCCATCAATGATACGTGGATCCAGGCCGGCATTGT
	GAGCTGGGGATTCGGCTGTGCCCGGCCTTTCCGGCCTGGTGTCTACACCCAGGTGCTAAGCTACACA
	GACTGGATTCAGAGAACCCTGGCTGAATCTCACTCAGGCATGTCTGGGGCCCGCCCAGGTGCCCCAG
	GATCCCACTCAGGCACCTCCAGATCCCACCCAGTGCTGCTGCTTGAGCTGTTGACCGTATGCTTGCT
	TGGGTCCCTGTGA
	ORF Start: ATG at 1		ORF Stop: TGA at 949
	SEQ ID NO: 118	316 aa	MW at 33574.2 kD
NOV25a,	MGLRAGPILLLLLWLLPGAHWDVLPSECGHSKEAGRIVGGQDTQEGRWPWQVGLWLTSVGHVCGGSL
CG147274-01
Protein Sequence	IHPRWVLTAAHCFLRSEDPGLYHVKVGGLTPSLSEPHSALVAVRRLLVHSSYHGTTTSGDIALMELD
	SPLQASQFSPICLPGPQTPLAIGTVCWVNGLGPTSHPALASVLQEVAVPLLDSNMCELMYHLGEPSL
	AGQRLIQDDMLCAGSVQGKKDSCQGDSGGPLVCPINDTWIQAGIVSWGFGCARPFRPGVYTQVLSYT
	DWIQRTLAESHSGMSGARPGAPGSHSGTSRSHPVLLLELLTVCLLGSL

[0476] Further analysis of the NOV25a protein yielded the following properties shown in Table 25B.

TABLE 25B
Protein Sequence Properties NOV25a
PSort analysis:   0.9190 probability located in plasma membrane;
                  0.3000 probability located in lysosome (membrane);
                  0.1000 probability located in endoplasmic reticulum
                  (membrane); 0.1000 probability located in
                  endoplasmic reticulum (lumen)
SignalP analysis: Cleavage site between residues 22 and 23

[0477] A search of the NOV25a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 25C.

TABLE 25C
Geneseq Results for NOV25a
		NOV25a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAU98887	Human protease PRTS5 -	1 . . . 316	304/316 (96%)	0.0
	Homo sapiens, 304 aa.	1 . . . 304	304/316 (96%)
	[WO200238744-A2,
	16-MAY-2002]
AAW77303	Amino acid sequence of	28 . . . 316	285/289 (98%)	e−171
	SP002LA, a homologue of	1 . . . 289	285/289 (98%)
	HELA2 - Homo sapiens, 289
	aa. [WO9836054-A1,
	20-AUG-1998]
ABG64545	Human albumin fusion	5 . . . 275	121/275 (44%)	1e−63
	protein #1220 - Homo	6 . . . 276	168/275 (61%)
	sapiens, 290 aa.
	[WO200177137-A1,
	18-OCT-2001]
AAB73945	Human protease T - Homo	5 . . . 275	121/275 (44%)	1e−63
	sapiens, 290 aa.	6 . . . 276	168/275 (61%)
	[WO200116293-A2,
	08-MAR-2001]
AAE03821	Human gene 4 encoded	5 . . . 275	121/275 (44%)	1e−63
	secreted protein HWHIH10,	6 . . . 276	168/275 (61%)
	SEQ ID NO: 67 - Homo sapiens,
	290 aa.
	[WO200136440-A1,
	25-MAY-2001]

[0478] In a BLAST search of public sequence datbases, the NOV25a protein was found to have homology to the proteins shown in the BLASTP data in Table 25D.

TABLE 25D
Public BLASTP Results for NOV25a
		NOV25a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q91XC4	Similar to distal intestinal	1 . . . 316	202/317 (63%)	e−114
	serine protease - Mus	1 . . . 310	235/317 (73%)
	musculus (Mouse), 310 aa.
Q9QYZ9	Distal intestinal serine	1 . . . 316	201/317 (63%)	e−113
	protease - Mus musculus	1 . . . 310	233/317 (73%)
	(Mouse), 310 aa.
Q9BQR3	Marapsin precursor (EC	5 . . . 275	121/275 (44%)	3e−63
	3.4.21.−) - Homo sapiens	6 . . . 276	168/275 (61%)
	(Human), 290 aa.
Q8R1A6	RHKIEN cDNA 2010001P08	24 . . . 305	142/293 (48%)	5e−62
	gene - Mus musculus	41 . . . 329	174/293 (58%)
	(Mouse), 331 aa.
Q9DGR3	Embryonic serine protease-1 -	25 . . . 304	123/288 (42%)	1e−59
	Xenopus laevis (African	29 . . . 308	165/288 (56%)
	clawed frog), 317 aa.

[0479] PFam analysis predicts that the NOV25a protein contains the domains shown in the Table 25E.

Domain Analysis of NOV25a
		Identities/
	NOV25a	Similarities for
Pfam Domain	Match Region	the Matched Region	Expect Value
trypsin	37 . . . 271	109/266 (41%)	1.7e−79
		176/266 (66%)

Example 26

[0480] 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	970 bp
NOV26a,	CACAAGAACAATATGCAGCTGAGATGAGTAAAGCTATTGCTTTTGAGATCATTCAGAAATACGAGCC
CG147351-01
DNA Sequence	TATCGAAGAAGTTAGGAAAGCACACCAAATGTCATTAGAAGGTTTTACAAGATACATGGATTCACGT
	GAATGTCTACTGTTTAAAAATGAATGTAGAAAAGTTTATCAAGATATGACTCATCCATTAAATGATT
	ATTTTATTTCATCTTCACATAACACATATTTGGTATCTGATCAATTATTGGGACCAAGTGACCTTTG
	GGGATATGTAAGTGCCCTTGTGAAAGGATGCCGTTGTTTGGAGATTGACTGCTGGGATGGAGCACAA
	AATGAACCTGTTGTATATCATGGCTACACACTCACAAGCAAACTTCTGTTTAAAACTGTTATCCAAG
	CTATACACAAGTATGCATTCATGGTGGCTTTAAATTTCCAGACCCCTGGTCTGCCCATGGATCTGCA
	AAATGGGAAATTTTTGGATAATGGTGGTTCTGGATATATTTTGAAACCACATTTCTTAAGAGAGAGT
	AAATCATACTTTAACCCAAGTAACATAAAAGAGGGTATGCCAATTACACTTACAATAAGGCTCATCA
	GTGGTATCCAGTTGCCTCTTACTCATTCATCATCTAACAAAGGTGATTCATTAGTAATTATAGAAGT
	TTTTGGTGTTCCAAATGATCAAATGAAGCAGCAGACTCGTGTAATTAAAAAAAATGCTTTTAGTCCA
	AGATGGAATGAAACATTCACATTTATTATTCATGTCCCAGAATTGGCATTGATACGTTTTGTTGTTG
	AAGGTCAAGGTTTAATAGCAGGAAATGAATTTCTTGGGCAATATACTTTGCCACTTCTATGCATGAA
	CAAAGGTTATCGTCGTATTCCTCTGTTTTCCAGAATGGGTGAGAGCCTTGAGCCTGCTTCACTGTTT
	GTTTATGTTTGGTACGTCAGATAACAGCTAAG
	ORF Start: ATG at 24		ORF Stop: TAA at 960
	SEQ ID NO: 120	312 aa	MW at 35720.0 kD
NOV26a,	MSKAIAFEIIQKYEPIEEVRKAHQMSLEGFTRYMDSRECLLFKNECRKVYQDMTHPLNDYFISSSHN
CG147351-01
Protein Sequence	TYLVSDQLLGPSDLWGYVSALVKGCRCLEIDCWDGAQNEPVVYHGYTLTSKLLFKTVIQAIHKYAFM
	VALNFQTPGLPMDLQNGKFLDNGGSGYILKPHFLRESKSYFNPSNIKEGMPITLTIRLISGIQLPLT
	HSSSNKGDSLVIIEVFGVPNDQMKQQTRVIKKNAFSPRWNETFTFIIHVPELALIRFVVEGQGLIAG
	NEFLGQYTLPLLCMNKGYRRIPLFSRMGESLEPASLFVYVWYVR

[0481] Further analysis of the NOV26a protein yielded the following properties shown in Table 26B.

TABLE 26B
Protein Sequence Properties NOV26a
PSort     0.5844 probability located in microbody (peroxisome);
analysis: 0.1814 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:

[0482] 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
		Residues/	Identities/
Geneseq	Protein/Organism/Length	Match	Similarities for the	Expect
Identifier	[Patent #, Date]	Residues	Matched Region	Value
AAU76817	Human phospholipase C	134 . . . .312	179/179 (100%)	e−101
	16839 polypeptide - Homo	430 . . . 608	179/179 (100%)
	sapiens, 608 aa.
	[WO200206302-A2,
	24-JAN-2002]
ABB90425	Human polypeptide SEQ ID	134 . . . 312	179/179 (100%)	e−101
	NO 2801 - Homo sapiens,	1 . . . 179	179/179 (100%)
	179 aa. [WO200190304-A2,
	29-NOV-2001]
AAU87271	Novel central nervous	134 . . . 312	179/179 (100%)	e−101
	system protein #181 - Homo	76 . . . 254	179/179 (100%)
	sapiens, 254 aa.
	[WO200155318-A2,
	02-AUG-2001]
AAM95867	Human reproductive system	134 . . . 312	178/179 (99%)	e−100
	related antigen SEQ ID NO:	76 . . . 254	178/179 (99%)
	4525 - Homo sapiens, 254
	aa. [WO200155320-A2,
	02-AUG-2001]
AAU22938	Novel human enzyme	134 . . . .312	178/179 (99%)	e−100
	polypeptide #24 - Homo	76 . . . 254	178/179 (99%)
	sapiens, 254 aa.
	[WO200155301-A2,
	02-AUG-20011

[0483] In a BLAST search of public sequence datbases, the NOV26a protein was found to have homology to the proteins shown in the BLASTP data in Table 26D.

TABLE 26D
Public BLASTP Results for NOV26a
		NOV26a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
BAC05152	CDNA FLJ40406 fis, clone	134 . . . 312	179/179(100%)	e−101
	TESTI2037534, weakly similar to	212 . . . 390	179/179(100%)
	1-PHOSPHATIDYLINOSITOL−4,5−B
	ISPHOSPHATE
	PHOSPHODIESTERASE DELTA 1
	(EC 3.1.4.11) - Homo sapiens
	(Human), 390 aa.
Q96J70	Testis-development related NYD-SP27 -	134 . . . 312	178/179 (99%)	e−100
	Homo sapiens (Human), 504 aa.	326 . . . 504	178/179 (99%)
Q95JSO	Hypothetical 74.4 kDa protein -	134 . . . 312	172/179 (96%)	2e−97
	Macaca fascicularis (Crab eating	462 . . . 640	177/179 (98%)
	macaque)(Cynomolgus monkey), 640
	aa.
Q95JS1	Hypothetical 74.6 kDa protein -	134 . . . 312	172/179 (96%)	2e−97
	Macaca fascicularis (Crab eating	463 . . . 641	177/179 (98%)
	macaque)(Cynomolgus monkey), 641
	aa.
AAM95914	PLC-zeta - Mus musculus (Mouse),	134 . . . 312	135/181 (74%)	7e−73
	647 aa.	467 . . . 646	158/181 (86%)

[0484] PFam analysis predicts that the NOV26a protein contains the domains shown in the Table 26E.

TABLE 26E
Domain Analysis of NOV26a
		Identities/
		Similarities
	NOV26a	for the Matched
Pfam Domain	Match Region	Region	Expect Value
PI-PLC-X	52 . . . 133	45/83 (54%)	4.3e−36
		66/83 (80%)
PI-PLC-Y	134 . . . 169	25/43 (58%)	2.9e−17
		33/43 (77%)
C2	188 . . . 276	33/97 (34%)	4.9e−20
		73/97 (75%)

Example 27

[0485] 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	3136 bp
NOV27a,	AGGGAGTCGTGTCGGCGCCACCCCGGCCCCCGAGCCCGCAGATTGCCCACCGAAGCTCGTGTGTGCA
CG147419-01
DNA Sequence	CCCCCGATCCCGCCAGCCACTCGCCCCTGGCCTCGCGGGCCGTGTCTCCGGCATCATGTGTGGTATA
	TTTGCTTACTTAAACTACCATGTTCCTCGAACGAGACGAGAAATCCTGGAGACCCTAATCAAAGGCC
	TTCAGAGACTGGAGTACAGAGGATATGATTCTGCTGGTGTGGGATTTGATGGAGGCAATGATAAAGA
	TTGGGAAGCCAATGCCTGCAAAACCCAGCTTATTAAGAAGAAAGGAAAAGTTAAGGCACTGGATGAA
	GAAGTTCACAAGCAACAAGATATGGATTTGGATATAGAATTTGATGTACACCTTGGAATAGCTCATA
	CCCGTTGGGCAACACATGGAGAACCCAGTCCTGTCAATAGCCACCCCCAGCGCTCTGATAAAAATAA
	TGAATTTATCGTTATTCACAATGGCATCATCACCAACTACAAAGACTTGAAAAAGTTTTTGGAAAGC
	AAAGGCTATGACTTCGAATCTGAAACAGACACAGAGACAATTGCCAAGCTCGTTAAGTATATGTATG
	ACAATCGGGAAAGTCAAGATACCAGCTTTACTACCTTGGTGGAGAGAGTTATCCAACAATTGGAAGG
	TGCTTTTGCACTTGTGTTTAAAAGTGTTCATTTTCCCGGGCAAGCAGTTGGCACAAGGCGAGGTAGC
	CCTCTGTTGATTGGTGTACGGAGTGAACATAAACTTTCTACTGATCACATTCCTATACTCTACAGAA
	CAGCTAGGACTCAGATTGGATCAAAATTCACACGGTGGGGATCACAGGGAGAAAGAGGCAAAGACAA
	GAAAGGAAGCTGCAATCTCTCTCGTGTGGACAGCACAACCTGCCTTTTCCCGGTGGAAGAAAAAGCA
	GTGGAGTATTACTTTGCTTCTGATGCAAGTGCTGTCATAGAACACACCAATCGCGTCATCTTTCTGG
	AAGATGATGATGTTGCAGCAGTAGTGGATGGACGTCTTTCTATCCATCGAATTAAACGAACTGCAGG
	AGATCACCCCGGACGAGCTGTGCAAACACTCCAGATGGAACTCCAGCAGATCATGAAGGGCAACTTC
	AGTTCATTTATGCAGAAGGAAATATTTGAGCAGCCAGAGTCTGTCGTGAACACAATGAGAGGAAGAG
	TCAACTTTGATGACTATACTGTGAATTTGGGTGGTTTGAAGGATCACATAAAGGAGATCCAGAGATG
	CCGGCGTTTGATTCTTATTGCTTGTGGAACAAGTTACCATGCTGGTGTAGCAACACGTCAAGTTCTT
	GAGGAGCTGACTGAGTTGCCTGTGATGGTGGAACTAGCAAGTGACTTCCTGGACAGAAACACACCAG
	TCTTTCGAGATGATGTTTGCTTTTTCCTTAGTCAATCAGGTGAGACAGCAGATACTTTGATGGGTCT
	TCGTTACTGTAAGGAGAGAGGAGCTTTAACTGTGGGGATCACAAACACAGTTGGCAGTTCCATATCA
	CGGGAGACAGATTGTGGAGTTCATATTAATGCTGGTCCTGAGATTGGTGTGGCCAGTACAAAGGCTT
	ATACCAGCCAGTTTGTATCCCTTGTGATGTTTGCCCTTATGATGTGTGATGATCGGATCTCCATGCA
	AGAAAGACGCAAAGAGATCATGCTTGGATTGAAACGGCTGCCTGATTTGATTAAGGAAGTACTGAGC
	ATGGATGACGAAATTCAGAAACTAGCAACAGAACTTTATCATCAGAAGTCAGTTCTGATAATGGGAC
	GAGGCTATCATTATGCTACTTGTCTTGAAGGGGCACTGAAAATCAAAGAAATTACTTATATGCACTC
	TGAAGGCATCCTTGCTGGTGAATTGAAACATGGCCCTCTGGCTTTGGTGGATAAATTGATGCCTGTG
	ATCATGATCATCATGAGAGATCACACTTATGCCAAGTGTCAGAATGCTCTTCAGCAAGTGGTTGCTC
	GGCAGGGGCGGCCTGTGGTAATTTGTGATAAGGAGGATACTGAGACCATTAAGAACACAAAAAGAAC
	GATCAAGGTGCCCCACTCAGTGGACTGCTTGCAGGGCATTCTCAGCGTGATCCCTTTACAGTTGCTG
	GCTTTCCACCTTGCTGTGCTGAGAGGCTATGATGTTGATTTCCCACGGAATCTTGCCAAATCTGTGA
	CTGTAGAGTGAGGAATATCTATACAAAATGTACGAAACTGTATGATTAAGCAACACAAGACACCTTT
	TGTATTTAAAACCTTGATTTAAAATATCACCCCTTGAAGCCTTTTTTTAGTAAATCCTTATTTATAT
	ATCAGTTATAATTATTCCACTCAATATGTGATTTTTGTGAAGTTACCTCTTACATTTTCCCAGTAAT
	TTGTGGAGGACTTTGAATAATGGAATCTATATTGGAATCTGTATCAGAAAGATTCTAGCTATTATTT
	TCTTTAAAGAATGCTGGGTGTTGCATTTCTGGACCCTCCACTTCAATCTGAGAAGACAATATGTTTC
	TAAAAATTGGTACTTGTTTCACCATACTTCATTCAGACCAGTGAAAGAGTAGTGCATTTAATTGGAG
	TATCTAAAGCCAGTGGCAGTGTATGCTCATACTTGGACAGTTAGGGAAGGGTTTGCCAAGTTTTAAG
	AGAAGATGTGATTTATTTTGAAATTTGTTTCTGTTTTGTTTTTAAATCAAACTGTAAAACTTAAAAC
	TGAAAAATTTTATTGGTAGGATTTATATCTAAGTTTGGTTAGCCTTAGTTTCTCAGACTTGTTGTCT
	ATTATCTGTAGGTGGAAGAAATTTAGGAAGCGAAATATTACAGTAGTGCATTGGTGGGTCTCAATCC
	TTAACATATTTGCACAATTTTATAGCACAAACTTTAAATTCAAGCTGCTTTGGACAACTGACAATAT
	GATTTTAAATTTGAAGATGGGATGTGTACATGTTGGGTATCCTACTACTTTGTGTTTTCATCTCCTA
	AAAGTGTTTTTTATTTCCTTGTATCTGTAGTCTTTTATTTTTTAAATGACTGCTGAATGACATATTT
	TATCTTGTTCTTTAAAATCACAACACAGAGCTGCTATTAAATTAATATTGATAT
	ORF Start: ATG at 123		ORF Stop: TGA at 2220
	SEQ ID NO: 122	699 aa	MW at 78793.6 kD
NOV27a,	MCGIFAYLNYHVPRTRREILETLIKGLQRLEYRGYDSAGVGFDGGNDKDWEANACKTQLIKKKGKVK
CG147419-01
Protein Sequence	ALDEEVHKQQDMDLDIEFDVHLGIAHTRWATHGEPSPVNSHPQRSDKNNEFIVIHNGIITNYKDLKK
	FLESKGYDFESETDTETIAKLVKYMYDNRESQDTSFTTLVERVIQQLEGAFALVFKSVHFPGQAVGT
	RRGSPLLIGVRSEHKLSTDHIPILYRTARTQIGSKFTRWGSQGERGKDKKGSCNLSRVDSTTCLFPV
	EEKAVEYYFASDASAVIEHTNRVIFLEDDDVAAVVDGRLSIHRIKRTAGDHPGRAVQTLQMELQQIM
	KGNFSSFMQKEIFEQPESVVNTMRGRVNFDDYTVNLGGLKDHIKEIQRCRRLILIACGTSYHAGVAT
	RQVLEELTELPVMVELASDFLDRNTPVFRDDVCFFLSQSGETADTLMGLRYCKERGALTVGITNTVG
	SSISRETDCGVHINAGPEIGVASTKAYTSQFVSLVMFALMMCDDRISMQERRKEIMLGLKRLPDLIK
	EVLSMDDEIQKLATELYHQKSVLIMGRGYHYATCLEGALKIKEITYMHSEGILAGELKHGPLALVDK
	LMPVIMIIMRDHTYAKCQNALQQVVARQGRPVVICDKEDTETIKNTKRTIKVPHSVDCLQGILSVIP
	LQLLAFHLAVLRGYDVDFPRNLAKSVTVE

[0486] Further analysis of the NOV27a protein yielded the following properties shown in Table 27B.

TABLE 27B
Protein Sequence Properties NOV27a
PSort     0.4902 probability located in mitochondrial inner membrane;
analysis: 0.4400 probability located in plasma membrane;
          0.3000 probability located in
          microbody (peroxisome); 0.2000 probability located in
          endoplasmic reticulum (membrane)
SignalP   No Known Signal Sequence Predicted
analysis:

[0487] 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
ABB05747	Human GFAT1L protein	1 . . . 699	698/699 (99%)	0.0
	SEQ ID NO: 1 - Homo	1 . . . 699	698/699 (99%)
	sapiens, 699 aa.
	[WO200196574-A1,
	20-DEC-2001]
AAY90260	Human GFAT protein	1 . . . 681	681/699 (97%)	0.0
	sequence - Homo sapiens,	1 . . . 681	681/699 (97%)
	681 aa. [WO200037617-AI,
	29-JUN-2000]
AAR43348	Human GFAT - Homo	1 . . . 699	680/699 (97%)	0.0
	sapiens, 681 aa.	1 . . . 681	680/699 (97%)
	[WO9321330-A,
	28-OCT-1993]
AAY90261	Human GFAT II protein	1 . . . 699	541/701 (77%)	0.0
	sequence - Homo sapiens,	1 . . . 682	618/701 (87%)
	682 aa. [WO200037617-Al,
	29-JUN-2000]
AW37772	Huma	1 . . . 699	541/701 (77%)	0.0
	glutamine: fructose-6-	1 . . . 682	618/701 (87%)
	phosphate amidotransferase
	TGC028−4 - Homo sapiens,
	682 aa. [EP824149−A2,
	18-FEB-1998]

[0488] 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
Q99MJ4	Glutamine: fructose-6-phosphate	1 . . . 699	688/699 (98%)	0.0
	amidotransferase 1 muscle	1 . . . 697	690/699 (98%)
	isoform GFAT1M - Mus
	musculus (Mouse), 697 aa.
A45055	glutamine--fructose-6-phosphatae	1. . . 699	681/699 (97%)	0.0
	transaminase (isomerizing)(EC	1 . . . 681	681/699 (97%)
	2.6.1.16) - human, 681 aa.
Q06210	Glucosamine--fructose-6-phospha	2 . . . 699	680/698 (97%)	0.0
	te aminotransferase [isomerizing]	1. . . 680	680/698 (97%)
	1 (EC 2.6.1.16)(Hexosephosphate
	aminotransferase 1)
	(D-fructose-6- phosphate
	amidotransferase 1)(GFAT 1)
	(GFAT1) - Homo sapiens
	(Human), 680 aa.
BAB31882	Gfptl protein - Mus musculus	1 . . . 699	674/699 (96%)	0.0
	(Mouse), 681 aa.	1 . . . 681	676/699 (96%)
P47856	Glucosamine--fructose-6-phosphate	2 . . . 699	673/698 (96%)	0.0
	aminotransferase [isomerizing]	1 . . . 680	675/698 (96%)
	1 (EC 2.6.1.16)(Hexosephosphate
	aminotransferase 1)
	(D-fructose-6- phosphate
	amidotransferase 1)(GFAT 1)
	(GFAT1) - Mus musculus
	(Mouse), 680 aa.

[0489] PFam analysis predicts that the NOV27a protein contains the domains shown in the Table 27E.

TABLE 27E
Domain Analysis of NOV27a
		Identities/
		Similarities
	NOV27a	for the Matched
Pfam Domain	Match Region	Region	Expect Value
GATase_2	2 . . . 210	91/219(42%)	4.6e−127
		202/219 (92%)
SIS	378 . . . 512	52/156 (33%)	2.2e−48
		118/156 (76%)
SIS	549 . . . 685	52/156 (33%)	3.3e−46
		124/156 (79%)

Example 28

[0490] 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	2521 bp
NOV28a,	ACTCTGCCCGACTCAGGGCTCCAGCGTGACATGGCTGAAGCGCACCAGGCCGTGGGCTTCCGACCCT
CG148102-01
DNA Sequence	CGCTGACCTCGGACGGGGCTGAAGTGGAACTCAGTGCCCCTGTGCTGCAGGAGATCTACCTCTCTGG
	CCTGCGCTCCTGGAAAAGGCATCTCTCACGTTTCTGGGTGCAGAATGACTTTCTCACCGGTGTGTTT
	CCTGCCAGCCCCCTCAGTTGGCTTTTCCTCTTCAGTGCCATCCAGCTTGCCTGGTTCCTCCAGCTGG
	ATCCTTCCTTAGGACTGATGGAGAAGATCAAAGAGTTGCTGCGGGGGGTCCTGGCAGCCGCGCTGTT
	TGCCTCGTGTTTGTGGGGAGCCCTGATCTTCACACTGCACGTGGCCCTGAGGCTGCTTCTGTCCTAC
	CACGGCTGGCTTCTTGAGCCCCACGGAGCCATGTCCTCCCCCACCAAGACCTGGCTGGCCCTGGTCC
	GCATCTTCTCTGGCCGCCACCCGATGCTGTTCAGTTACCAGCGCTCCCTGCCACGCCAGCCCGTGCC
	CTCTGTGCAGGACACCGTGCGCAAGTACCTGGAGTCGGTCCGGCCCATCCTCTCCGACGAGGACTTC
	GACTGGACCGCGGTCCTGGCGCAGGAATTCCTGAGGCTGCAGGCGTCGCTGCTGCAGTGGTACCTGC
	GGCTCAAGTCCTGGTGGGCGTCCAATTATGTGAGTGACTGGTGGGAGGAATTTGTGTACCTGCGCTC
	CCGAAATCCGCTGATGGTGAACAGCAACTATTACATGATGGACTTCCTGTATGTCACACCCACGCCT
	CTGCAGGCAGCTCGCGCTGGGAATGCCGTCCATGCCCTCCTCCTGTACCGCCACCGCCTGAACCGCC
	AGGAGATACCCCCGGTGAGACTGATGGGAATGCGCCCCTTATGCTCTGCCCAGTACGAGAAGATCTT
	CAACACCACGCGGATTCCAGGGGTCCAAAAAGGTGAGACCATCCGCCACCTCCATGACAGCCAACAC
	GTGGCTGTCTTCCACCGGGGCCGATTCTTCCGCATGGGGACCCACTCCCGAAACAGCCTGCTTTCCC
	CGAGAGCCCTGGAGCAGCAGTTTCAGAGAATCCTGGATGATCCCTCACCGGCCTGCCCCCACGAGGA
	ACATCTGGCAGCTCTGACAGCTGCTCCCAGGGGCACGTGGGCCCAGGTGCGGACATCCCTGAAGACC
	CAGGCAGCGGAGGCCCTGGAGGCGGTGGAAGGGGCCGCTTTCTTTGTGTCACTGGATGCTGAGCCCG
	CGGGGCTCACCAGGGAGGACCCGGCAGCGTCGTTGGATGCCTACGCCCATGCTCTGCTGGCCGGCCG
	GGGCCATGATCGGTGGTTTGACAAATCCTTCACCCTAATCGTCTTCTCTAACGGGAAGCTGGGCCTC
	AGCGTGGAGCACTCCTGGGCCGACTGCCCCATCTCAGGACACATGTGGGAGTTCACTCTGGCTACAG
	AATGCTTTCAGCTGGGCTACTCAACAGACGGCCACTGCAAGGGGCACCCGGACCCCACACTACCCCA
	GCCCCAGCGGCTGCAATGGGACCTTCCAGACCAGGTGAGGCTGGGTATCTCTCTAGCCCTGAGGGGA
	GCCAAGATCTTGTCTGAAAATGTCGACTGCCATGTCGTTCCATTCTCCCTATTTGGCAAGAGCTTCA
	TCCGACGCTGCCACCTCTCTTCAGACAGCTTCATCCAGATCGCCTTGCAACTGGCCCACTTCCGGGA
	CCCACAGTGCCTCGCCCTGTTCCGCGTGGCAGTGGACAAGCACCAGGCTCTGCTGAAGGCAGCCATG
	AGCGGGCAGGGAGTTGACCGCCACCTGTTTGCGCTGTACATCGTGTCCCGATTCCTCCACCTGCAGT
	CGCCCTTCCTGACCCAGGTCCATTCGGAGCAGTGGCAGCTGTCCACCAGCCAGATCCCTGTTCAGCA
	AATGCATCTGTTTGACGTCCACAATTACCCGGACTATGTTTCCTCAGGCGGTGGATTCGGGCCTGCT
	GATGACCATGGTTATGGTGTTTCTTATATCTTCATGGGGGATGGCATGATCACCTTCCACATCTCCA
	GCAAAAAATCAAGCACAAAAACGGATTCCCACAGGCTGGGGCAGCACATTGAGGACGCACTGCTGGA
	TGTGGCCTCCCTGTTCCAGGCGGGACAGCATTTTAAGCGCCGGTTCAGAGGGTCAGGGAAGGAGAAC
	TCCAGGCACAGGTGTGGATTTCTCTCCCGCCAGACTGGGGCCTCCAAGGCCTCAATGACATCCACCG
	ACTTCTGACTCCTTCCAGCAGGCAGCTGGCCTCTCCAAGGAATAAGGGTGAAATTGCCACAGCTGGC
	TGACACAGGACAGGGGCAACTGGTTTGGCAACCCCACATCCAGGCCAATAAAGATGTGTGAGCTGGG
	TGTGTGGTGTCTGCTATGCTCTTGGGCAGGGCAGGGGTAGAAGAGGTAAGGACCAGGGTGGAGGAGG
	ACAGAAGCTCCCATCCATTCCCAGGCCCAGCCAGGGATTCCC
	ORF Start: ATG at 31		ORF Stop: TGA at 2284
	SEQ ID NO: 124	751 aa	MW at 84918.2 kD
NOV28a,	MAEAHQAVGFRPSLTSDGAEVELSAPVLQEIYLSGLRSWKRHLSRFWVQNDFLTGVFPASPLSWLFL
CG148102-01
Protein Sequence	FSAIQLAWFLQLDPSLGLMEKIKELLRGVLAAALFASCLWGALIFTLHVALRLLLSYHGWLLEPHGA
	MSSPTKTWLALVRIFSGRHPMLFSYQRSLPRQPVPSVQDTVRKYLESVRPILSDEDFDWTAVLAQEF
	LRLQASLLQWYLRLKSWWASNYVSDWWEEFVYLRSRNPLMVNSNYYMMDFLYVTPTPLQAARAGNAV
	HALLLYRHRLNRQEIPPVRLMGMRPLCSAQYEKIFNTTRIPGVQKGETIRHLHDSQHVAVFHRGRFF
	RMGTHSRNSLLSPRALEQQFQRILDDPSPACPHEEHLAALTAAPRGTWAQVRTSLKTQAAEALEAVE
	GAAFFVSLDAEPAGLTREDPAASLDAYAHALLAGRGHDRWFDKSFTLIVFSNGKLGLSVEHSWADCP
	ISGHMWEFTLATECFQLGYSTDGHCKGHPDPTLPQPQRLQWDLPDQVRLGISLALRGAKILSENVDC
	HVVPFSLFGKSFIRRCHLSSDSFIQIALQLAHFRDPQCLALFRVAVDKHQALLKAAMSGQGVDRHLF
	ALYIVSRFLHLQSPFLTQVHSEQWQLSTSQIPVQQMHLFDVHNYPDYVSSGGGFGPADDHGYGVSYI
	FMGDGMITFHISSKKSSTKTDSHRLGQHIEDALLDVASLFQAGQHFKRRFRGSGKENSRHRCGFLSR
	QTGASKASMTSTDF
	SEQ ID NO: 125	2748 bp
NOV28b,	CGAGAGACAGGAATCGGGGTTTCTGGGTGACGGTGATCTCGGGGTGGGCAGGACTCCAAAGGCCCGT
CG148102-02
DNA Sequence	CGACCCGGTGGTGGACTCCTTGCACTGGGATTGGACATATGCAAGCGGGAGATTTGGGGCCGGCGCT
	CAAAATCGGGGGGCGGGGGTGGACTCGGGTTTGGACCCCAGGATCCGATCAGCGGACCCTTGATTCA
	ACGTGGGCTCCAGCGTGACATGGCTGAAGCGCACCAGGCCGTGGGCTTCCGACCCTCGCTGACCTCG
	GACGGGGCTGAAGTGGAACTCAGTGCCCCTGTGCTGCAGGAGATCTACCTCTCTGGCCTGCGCTCCT
	GGAAAAGGCATCTCTCACGTTTCTGGAATGACTTTCTCACCGGTGTGTTTCCTGCCAGCCCCCTCAG
	TTGGCTTTTCCTCTTCAGTGCCATCCAGCTTGCCTGGTTCCTCCAGCTGGATCCTTCCTTAGGACTG
	ATGGAGAAGATCAAAGAGTTGCTGCCTGACTGGGGTGGACAACACCACGGGCTCCGGGGGGTCCTGG
	CAGCCGCGCTGTTTGCCTCGTGTTTGTGGGGAGCCCTGATCTTCACACTGCACGTGGCCCTGAGGCT
	GCTTCTGTCCTACCACGGCTGGCTTCTTGAGCCCCACGGAGCCATGTCCTCCCCCACCAAGACCTGG
	CTGGCCCTGGTCCGCATCTTCTCTGGCCGCCACCCGATGCTGTTCAGTTACCAGCGCTCCCTGCCAC
	GCCAGCCCGTGCCCTCTGTGCAGGACACCGTGCGCAAGTACCTGGAGTCGGTCCGGCCCATCCTCTC
	CGACGAGGACTTCGACTGGACCGCGGTCCTGGCGCAGGAATTCCTGAGGCTGCAGGCGTCACTGCTG
	CAGTGGTACCTGCGGCTCAAGTCCTGGTGGGCGTCCAATTATGTCAGTGACTGGTGGGAGGAATTTG
	TGTACCTGCGCTCCCGAAATCCGCTGATGGTGAACAGCAACTATTACATGATGGACTTCCTGTATGT
	CACACCCACGCCTCTGCAGGCAGCTCGCGCTGGGAATGCCGTCCATGCCCTCCTCCTGTACCGCCAC
	CGCCTGAACCGCCAGGAGATACCCCCGACTTTGCTGATGGGAATGCGCCCCTTATGCTCTGCCCAGT
	ACGAGAAGATCTTCAACACCACGCGGATTCCAGGGGTCCAAAAAGACTACATCCGCCACCTCCATGA
	CAGCCAACACGTGGCTGTCTTCCACCGGGGCCGATTCTTCCGCATGGGGACCCACTCCCGAAACAGC
	CTGCTTTCCCCGAGAGCCCTGGAGCAGCAGTTTCAGAGAATCCTGGATGATCCCTCACCGGCCTGCC
	CCCACGAGGAACATCTGGCAGCTCTGACAGCTGCTCCCAGGGGCACGTGGGCCCAGGTGCGGACATC
	CCTGAAGACCCAGGCAGCGGAGGCCCTGGAGGCGGTGGAAGGGGCCGCTTTCTTTGTGTCACTGGAT
	GCTGAGCCCGCGGGGCTCACCAGGGAGGACCCGGCAGCGTCGTTGGATGCCTACGCCCATGCTCTGC
	TGGCTGGCCGGGGCCATGATCGCTGGTTTGACAAATCCTTCACCCTAATCGTCTTCTCTAACGGGAA
	GCTGGGCCTCAGCGTGGAGCACTCCTGGGCCGACTGCCCCATCTCAGGACACATGTGGGAGTTCACT
	CTGGCTACAGAATGCTTTCAGCTGGGCTACTCAACAGATGGCCACTGCAAGGGGCACCCGGACCCCA
	CACTACCCCAGCCCCAGCGGCTGCAATGGGACCTTCCAGACCAGATCCACTCCTCCATCTCTCTAGC
	CCTGAGGGGAGCCAAGATCTTGTCTGAAAATGTCGACTGCCATGTCGTTCCATTCTCCCTATTTGGC
	AAGAGCTTCATCCGACGCTGCCACCTCTCTTCAGACAGCTTCATCCAGATCGCCTTGCAACTGGCCC
	ACTTCCGGGACAGGGGTCAATTCTGCCTGACTTATGAGTCGGCCATGACTCGCTTATTCCTGGAAGG
	CCGGACGGAGACGGTGCGGTCTTGCACGAGGGAGGCCTGCAACTTTGTCAGGGCCATGGAGGACAAA
	GAGAAGACGGACCCACAGTGCCTCGCCCTGTTCCGCGTGGCAGTGGACAAGCACCAGGCTCTGCTGA
	AGGCAGCCATGAGCGGGCAGGGAGTTGACCGCCACCTGTTTGCGCTGTACATCGTGTCCCGATTCCT
	CCACCTGCAGTCGCCCTTCCTGACCCAGGTCCATTCGGAGCAGTGGCAGCTGTCCACCAGCCAGATC
	CCTGTTCAGCAAATGCATCTGTTTGACGTCCACAATTACCCGGACTATGTTTCCTCAGGCGGTGGAT
	TCGGGCCTGCTGATGACCATGGTTATGGTGTTTCTTATATCTTCATGGGGGATGGCATGATCACCTT
	CCACATCTCCAGCAAAAAATCAAGCACAAAAACGGATTCCCACAGGCTGGGGCAGCACATTGAGGAC
	GCACTGCTGGATGTGGCCTCCCTGTTCCAGGCGGGACAGCATTTTAAGCGCCGGTTCAGAGGGTCAG
	GGAAGGAGAACTCCAGGCACAGGTGTGGATTTCTCTCCCGCCAGACTGGGGCCTCCAAGGCCTCAAT
	GACATCCACCGACTTCTGACTCCTTCCAGCAGGCAGCTGGCCTCTCCAAGGAATAAGGGTGAAATTG
	CCACAGCTGGCTGACACAGGACAGGGGCAACTGGTTTGGCAACCCCACATCCAGGCAAATAAAGATG
	G
	ORF Start: ATG at 221		ORF Stop: TGA at 2630
	SEQ ID NO: 126	803 aa	MW at 90987.8 kD
NOV28b,	MAEAHQAVGFRPSLTSDGAEVELSAPVLQEIYLSGLRSWKRHLSRFWNDFLTGVFPASPLSWLFLFS
CG148102-02
Protein Sequence	AIQLAWFLQLDPSLGLMEKIKELLPDWGGQHHGLRGVLAAALFASCLWGALIFTLHVALRLLLSYHG
	WLLEPHGAMSSPTKTWLALVRIFSGRHPMLFSYQRSLPRQPVPSVQDTVRKYLESVRPILSDEDFDW
	TAVLAQEFLRLQASLLQWYLRLKSWWASNYVSDWWEEFVYLRSRNPLMVNSNYYMMDFLYVTPTPLQ
	AARAGNAVHALLLYRHRLNRQEIPPTLLMGMRPLCSAQYEKIFNTTRIPGVQKDYIRHLHDSQHVAV
	FHRGRFFRMGTHSRNSLLSPRALEQQFQRILDDPSPACPHEEHLAALTAAPRGTWAQVRTSLKTQAA
	EALEAVEGAAFFVSLDAEPAGLTREDPAASLDAYAHALLAGRGHDRWFDKSFTLIVFSNGKLGLSVE
	HSWADCPISGHMWEFTLATECFQLGYSTDGHCKGHPDPTLPQPQRLQWDLPDQIHSSISLALRGAKI
	LSENVDCHVVPFSLFGKSFIRRCHLSSDSFIQIALQLAHFRDRGQFCLTYESAMTRLFLEGRTETVR
	SCTREACNFVRAMEDKEKTDPQCLALFRVAVDKHQALLKAAMSGQGVDRHLFALYIVSRFLHLQSPF
	LTQVHSEQWQLSTSQIPVQQMHLFDVHNYPDYVSSGGGFGPADDHGYGVSYIFMGDGMITFHISSKK
	SSTKTDSHRLGQHIEDALLDVASLFQAGQHFKRRFRGSGKENSRHRCGFLSRQTGASKASMTSTDF

[0491] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 28B.

TABLE 28B
Comparison of NOV28a against NOV28b.
	NOV28a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV28b	1 . . . 751	717/806 (88%)
	1 . . . 803	719/806 (88%)

[0492] Further analysis of the NOV28a protein yielded the following properties shown in Table 28C.

TABLE 28C
Protein Sequence Properties NOV28a
PSort analysis:   0.7900 probability located in plasma membrane;
                  0.6400 probability located in microbody
                  (peroxisome); 0.3000 probability
                  located in Golgi body; 0.2000 probability
                  located in endoplasmic reticulum (membrane)
SignalP analysis: Cleavage site between residues 5 and 6

[0493] 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 28D.

TABLE 28D
Geneseq Results for NOV28a
		NOV28a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAY79220	Human transferase	1 . . . 751	739/806 (91%)	0.0
	TRNSFS-12 - Homo sapiens,	1 . . . 803	742/806 (91%)
	803 aa. [WO200014251-A2,
	16-MAR-2000]
AA1E10322	Human carnitine	1 . . . 751	739/806 (91%)	0.0
	acyltransferase, 26886−	1 . . . 803	742/806 (91%)
	Homo sapiens, 803 aa.
	[WO200166759-A2,
	13-SEP-2001]
AAW14438	Type I carnitine palmitoyl	1 . . . 711	375/770 (48%)	0.0
	transferase-like protein -	1 . . . 766	495/770 (63%)
	Homo sapiens, 772 aa.
	[JP09009969-A,
	14-JAN-1997]
ABG04960	Novel human diagnostic	224 . . . 571	337/381 (88%)	0.0
	protein #4951 - Homo	92 . . . 471	339/381 (88%)
	sapiens, 521 aa.
	[WO200175067-A2,
	11-OCT-2001]
ABB67527	Drosophila melanogaster	1 . . . 717	315/775 (40%)	e−161
	polypeptide SEQ ID NO	1 . . . 765	447/775 (57%)
	29373 - Drosophila
	melanogaster, 780 aa.
	[WO200171042-A2,
	27-SEP-2001]

[0494] 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 28E.

TABLE 28E
Public BLASTP Results for NOV28a
		NOV28a	Identities/
		Residuesl	Similarities for
Protein Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q8TCG5	Carnitine	1 . . . 751	740/806 (91%)	0.0
	palmitoyltransferase IC -	1 . . . 803	742/806 (91%)
	Homo sapiens (Human), 803
	aa.
CAC88591	Sequence 1 from Patent	1 . . . 751	739/806 (91%)	0.0
	WO0166759 - Homo sapiens	1 . . . 803	742/806 (91%)
	(Human), 803 aa
AAH29104	Similar to carnitine	1 . . . 751	729/806 (90%)	0.0
	palmitoyltransferase IC -	1 . . . 792	731/806 (90%)
	Homo sapiens (Human), 792
	aa.
P32198	Carnitine	1 . . . 710	394/768 (51%)	0.0
	O-pahmitoyltransferase I,	1 . . . 765	524/768 (67%)
	mitochondrial liver isoform
	(EC 2.3.1.21) (CPT I)
	(CPTI-L) - Rattus norvegicus
	(Rat), 773 aa.
Q9BWK0	Similar to carnitine	1 . . . 690	381/748 (50%)	0.0
	palmitoyltransferase I, liver -	1 . . . 745	510/748 (67%)
	Homo sapiens (Human), 756
	aa.

[0495] PFam analysis predicts that the NOV28a protein contains the domains shown in the Table 28F.

TABLE 28F
Domain Analysis of NOV28a
	NOV28a	Identities/
	Match	Similarities for
Pfam Domain	Region	the Matched Region	Expect Value
Carn13 acyltransf	162 . . . 708	208/680 (31%)	1.5e−167
		437/680 (64%)

Example 29

[0496] 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: 127	1776 bp
NOV29a,	ACTAAAGCCTGCAGAGACCTCTGAAGGAAAACCTGTCCCGGGCTCTGTCACTTCACACCCATGGCTA
CG148431-01
DNA Sequence	ACCCTGGAGGTGGTGCTGTTTGCAACGGGAAACTTCACAATCACAAGAAACAGAGCAATGGCTCACA
	AAGCAGAAACTGCACAAAGAATGGAATAGTGAAGGAAGCCCAGCAAAATGGGAAGCCACATTTTTAT
	GATAAGCTCATTGTTGAATCGTTTGAGGAAGCACCCCTTCATGTTATGGTTTTCACTTACATGGGAT
	ATGGAATTGGAACCCTGTTTGGCTATCTCAGAGACTTTTTAAGAAACTGGGGAATAGAAAAATGCAA
	CGCAGCTGTGGAAAGAAAAGAACAAAAAGATTTTGTGCCACTGTATCAAGACTTTGAAAATTTTTAT
	ACAAGAAACCTTTACATGCGAATCAGAGACAACTGGAACCGGCCCATCTGCAGTGCCCCAGGGCCTC
	TGTTTGATTTGATGGAGAGGGTATCAGACGACTATAACTGGACGTTTAGGTTTACTGGAAGAGTCAT
	CAAAGATGTCATCAACATGGGCTCCTATAACTTCCTTGGTCTTGCAGCCAAGTATGATGAGTCTATG
	AGGACAATAAAGGATGTTTTAGAGGTGTATGGCACAGGCGTGGCCAGCACCAGGCATGAAATGGGCA
	CCTTGGATAAGCACAAGGAGTTGGAGGACCTTGTGGCTAAGTTCCTGAATGTGGAAGCAGCTATGGT
	CTTTGGGATGGGATTCGCAACTAACTCAATGAATATCCCAGCATTAGTTGGAAAGGGATGCCTCATT
	TTAAGTGATGAGTTAAACCACACATCGCTTGTGCTTGGGGCCCGACTCTCAGGTGCAACCATAAGAA
	TCTTCAAACACAACAACACACAAAGCCTAGAGAAGCTCCTGAGAGATGCTGTCATCTATGGCCAGCC
	TCGAACCCGCAGAGCTTGGAAAAAGATTCTCATCCTGGTGGAGGGTGTCTACAGCATGGAAGGTTCC
	ATCGTGCATCTGCCCCAGATCATAGCTCTAAAGAAGAAATACAAGGCTTACCTCTACATAGATGAAG
	CTCACAGTATTGGGGCCGTGGGCCCAACCGGCCGGGGTGTCACGGAGTTCTTTGGACTAGACCCTCA
	TGAAGTTGATGTGCTCATGGGCACATTCACCAAAAGTTTTGGAGCTTCAGGAGGTTACATAGCTGGA
	AGGAAGGACCTCGTGGATTATTTACGGGTTCACTCGCATAGTGCTGTTTATGCTTCATCCATGAGCC
	CACCGATAGCAGAGCAAATCATCAGATCACTAAAACTTATCATGGGACTGGATGGGACCACTCAAGG
	GCTGCAGAGAGTACAGCAACTTGCGAAAAACACAAGATACTTCAGACAAAGACTGCAGGAAATGGGA
	TTCATTATCTATGGCAATGAGAATGCTTCTGTTGTTCCTCTGCTTCTTTATATGCCTGGTAAAGTAG
	CGGCTTTTGCAAGGCATATGCTAGAGAAAAAAATTGGAGTGGTGGTCGTGGGATTTCCAGCCACTCC
	CCTCGCAGAAGCTCGGGCTCGGTTTTGTGTTTCAGCGGCACATACCCGGGAGATGTTAGACACGGTT
	TTAGAAGCTCTTGATGAAATGGGTGATCTCTTGCAACTGAAATATTCCCGGCACAAGAAGTCAGCAC
	GTCCTGAGCTCTATGATGAGACGAGCTTTGAACTCGAAGATTAAGTTTCCTGGTCCTGAATGACACA
	TAAAGACTTTGCGAGAAAGACCTCCCTCCTTGCC
	ORF Start: ATG at 61		ORF Stop: TAA at 1717
	SEQ ID NO: 128	1552 aa	MW at 62048.9 kD
NOV29a,	MANPGGGAVCNGKLHNHKKQSNGSQSRNCTKNGIVKEAQQNGKPHFYDKLIVESFEEAPLHVMVFTY
CG148431-01
Protein Sequence	MGYGIGTLFGYLRDFLRNWGIEKCNAAVERKEQKDFVPLYQDFENFYTRNLYMRIRDNWNRPICSAP
	GPLFDLMERVSDDYNWTFRFTGRVIKDVINMGSYNFLGLAAKYDESMRTIKDVLEVYGTGVASTRHE
	MGTLDKHKELEDLVAKFLNVEAAMVFGMGFATNSMNIPALVGKGCLILSDELNHTSLVLGARLSGAT
	IRIFKHNNTQSLEKLLRDAVIYGQPRTRRAWKKILILVEGVYSMEGSIVHLPQIIALKKKYKAYLYI
	DEAHSIGAVGPTGRGVTEFFGLDPHEVDVLMGTFTKSFGASGGYIAGRKDLVDYLRVHSHSAVYASS
	MSPPIAEQIIRSLKLIMGLDGTTQGLQRVQQLAKNTRYFRQRLQEMGFIIYGNENASVVPLLLYMPG
	KVAAFARHMLEKKIGVVVVGFPATPLAEARARFCVSAAHTREMLDTVLEALDEMGDLLQLKYSRHKK
	SARPELYDETSFELED
	SEQ ID NO: 129	1492 bp
NOV29b,	CACCGGATCCACCATGGCTAACCCTGGAGGTGGTGCTGTTTGCAACGGGAAACTTCACAATCACAAG
CG148431-02
DNA Sequence	AAACAGAGCAATGGCTCACAAAGCAGAAACTGCACAAAGAATGGAATAGTGAAGGAAGCCCAGGATT
	TTGTGCCACTGTATCAAGACTTTGAAAATTTTTATACAAGAAACCTTTACATGCGAATCAGAGACAA
	CTGGAACCGGCCCATCTGCAGTGCCCCAGGGCCTCTGTTTGATGTGATGGAGAGGGTATCGGACGAC
	TATAACTGGACGTTTAGGTTTACTGGAAGAGTCATCAAAGATGTCATCAACATGGGCTCCTATAACT
	TCCTTGGTCTTGCAGCCAAGTATGATGAGTCTATGAGGACAATAAAGGATGTTTTAGAGGTGTATGG
	CACAGGCGTGGCCAGCACCAGGCATGAAATGGGCACCTTGGATAAGCACAAGGAGTTGGAGGACCTT
	GTGGCTAAGTTCCTGAATGTGGAAGCAGCTATGGTCTTTGGGATGGGATTCGCAACTAACTCAATGA
	ATATCCCAGCATTAGTTGGAAAGGGATGCCTCATTTTAAGTGATGAGTTAAACCACACATCGCTTGT
	GCTTGGGGCCCGACTCTCAGGTGCAACCATAAGAATCTTCAAACACAACAACACACAAAGCCTAGAG
	AAGCTCCTGAGAGATGCTGTCATCTATGGCCAGCCTCGAACCCGCAGAGCTTGGAAAAAGATTCTCA
	TCCTGGTGGAGGGTGTCTACAGCATGGAAGGTTCCATCGTGCATCTGCCCCAGATCATAGCTCTAAA
	GAAGAAATACAAGGCTTACCTCTACATAGATGAAGCTCACAGTATTGGGGCCGTGGGCCCAACCGGC
	CGGGGTGTCACGGAGTTCTTTGGACTAGACCCTCATGAAGTTGATGTGCTCATGGGCACATTCACCA
	AAAGTTTTGGAGCTTCAGGAGGTTACATAGCTGGAAGGAAGGACCTCGTGGATTATTTACGGGTTCA
	CTCGCATAGTGCTGTTTATGCTTCATCCATGAGCCCACCGATAGCAGAGCAAATCATCAGATCACTA
	AAACTTATCATGGGACTGGATGGGACCACTCAAGGGCTGCAGAGAGTACAGCAACTTGCGAAAAACA
	CAAGATACTTCAGACAAAGACTGCAGGAAATGGGATTCATTATCTATGGCAATGAGAATGCTTCTGT
	TGTTCCTCTGCTTCTTTATATGCCTGGTAAAGTAGCGGCTTTTGCAAGGCATATGCTAGAGAAAAAA
	ATTGGAGTGGTGGTCGTGGGATTTCCAGCCACTCCCCTCGCAGAAGCTCGGGCTCGGTTTTGTGTTT
	CAGCGGCACATACCCGGGAGATGTTAGACACGGTTTTAGAAGCTCTTGATGAAATGGGTGATCTCTT
	GCAACTGAAATATTCCCGGCACAAGAAGTCAGCACGTCCTGAGCTCTATGATGAGACGAGCTTTGAA
	CTCGAAGATCTCGAGGGC
	ORF Start: ATG at 14		ORF Stop: at 1484
	SEQ ID NO: 130	490 aa	MW at 54766.5 kD
NOV29b,	MANPGGGAVCNGKLHNHKKQSNGSQSRNCTKNGIVKEAQDFVPLYQDFENFYTRNLYMRIRDNWNRP
CG148431-02
Protein Sequence	ICSAPGPLFDVMERVSDDYNWTFRFTGRVIKDVINMGSYNFLGLAAKYDESMRTIKDVLEVYGTGVA
	STRHEMGTLDKHKELEDLVAKFLNVEAAMVFGMGFATNSMNIPALVGKGCLILSDELNHTSLVLGAR
	LSGATIRIFKHNNTQSLEKLLRDAVIYGQPRTRRAWKKILILVEGVYSMEGSIVHLPQIIALKKKYK
	AYLYIDEAHSIGAVGPTGRGVTEFFGLDPHEVDVLMGTFTKSFGASGGYIAGRKDLVDYLRVHSHSA
	VYASSMSPPIAEQIIRSLKLIMGLDGTTQGLQRVQQLAKNTRYFRQRLQEMGFIIYGNENASVVPLL
	LYMPGKVAAFARHMLEKKIGVVVVGFPATPLAEARARFCVSAAHTREMLDTVLEALDEMGDLLQLKY
	SRHKKSARPELYDETSFELED

[0497] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 29B.

TABLE 29B
Comparison of NOV29a against NOV29b.
	NOV29a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV29b	98 . . . 552	438/455 (96%)
	36 . . . 490	440/455 (96%)

[0498] Further analysis of the NOV29a protein yielded the following properties shown in Table 29C.

TABLE 29C
Protein Sequence Properties NOV29a
PSort analysis:   0.4761 probability located in microbody (peroxisome);
                  0.3000 probability located in nucleus;
                  0.2077 probability located in lysosome (lumen);
                  0.1000 probability located in mitochondrial matrix
                  space
SignalP analysis: No Known Signal Sequence Predicted

[0499] 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
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAE22153	Human TRNFR-15 protein -	1 . . . 552	551/552 (99%)	0.0
	Homo sapiens, 552 aa.	1 . . . 552	552/552 (99%)
	[WO200226950-A2,
	04-APR-2002]
AAG73598	Human colon cancer antigen	201 . . . 549	269/352 (76%)	e−158
	protein SEQ ID NO: 4362 -	38 . . . 387	316/352 (89%)
	Homo sapiens, 391 aa.
	[WO200122920-A2,
	05-APR-2001]
ABB60160	Drosophila melanogaster	54 . . . 543	256/491 (52%)	e−151
	polypeptide SEQ ID NO	114 . . . 597	350/491 (71%)
	7272 - Drosophila
	melanogaster 597 aa.
	[WO200171042-A2,
	27-SEP-2001]
AAE21820	Human serine	47 . . . 276	228/230 (99%)	e−133
	palmitoyltransferase	1 . . . 230	230/230 (99%)
	(SPT)-like enzyme #2 -
	Homo sapiens, 230 aa.
	[WO200224884-A2,
	28-MAR-2002]
AAY32003	Rice serine	59 . . . 541	237/485 (48%)	e−133
	palmitoyltransferase Lcb2	5 . . . 483	333/485 (67%)
	subunit - Oryza sativa, 489
	aa. [WO9949021-A1,
	30-SEP-1999]

[0500] 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
Protein		Residues/	Identities/
Accession		Match	Similarities for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
Q9UGB6	DJ718P11.1.1 (Novel class II	102 . . . 515	414/414 (100%)	0.0
	aminotransferase similar to	1 . . . 414	414/414 (100%)
	serine palmotyltransferase
	(Isoform 1)) - Homo sapiens
	(Human), 414 aa (fragment).
O15270	Serine palmitoyltransferase 2	7 . . . 549	383/546 (70%)	0.0
	(EC 2.3.1.50) (Long chain	18 . . . 558	449/546 (82%)
	base biosynthesis protein 2)
	(LCB 2)
	(Serine-palmitoyl-CoA
	transferase 2) (SPT 2) -
	Homo sapiens (Human), 562
	aa.
P97363	Serine palmitoyltransferase 2	7 . . . 549	379/546 (69%)	0.0
	(EC 2.3.1.50) (Long chain	18 . . . 556	449/546 (81%)
	base biosynthesis protein 2)
	(LCB 2)
	(Serine-palmitoyl-CoA
	transferase 2) (SPT 2) - Mus
	musculus (Mouse), 560 aa.
JC5180	serine C-palmitoyltransferase	7 . . . 549	378/546 (69%)	0.0
	(EC 2.3.1.50) Lcb2 chain -	18 . . . 556	449/546 (82%)
	mouse, 560 aa.
O54694	Serine palmitoyltransferase 2	7 . . . 549	377/546 (69%)	0.0
	(EC 2.3.1.50) (Long chain	18 . . . 556	446/546 (81%)
	base biosynthesis protein 2)
	(LCB 2)
	(Serine-palmitoyl-CoA
	transferase 2) (SPT 2) -
	Cricetulus griseus (Chinese
	hamster), 560 aa.

[0501] PFam analysis predicts that the NOV29a protein contains the domains shown in the Table 29F.

TABLE 29F
Domain Analysis of NOV29a
		Identities/
		Similarities
	NOV29a	for the Matched
Pfam Domain	Match Region	Region	Expect Value
aminotran_1_2	193 . . . 521	71/363 (20%)	2.6e−29
		237/363 (65%)

Example 30

[0502] 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: 131	576 bp
NOV30a,	TGAGCCAGCCCCGGATGACCCTGCGACCTGGAACAATGCGGCTGGCCTGCATGTTCTCTTCCATCCT
CG148888-01
DNA Sequence	GCTGTTCGGAGCTGCAGGCCTCCTCCTCTTCATCAGCCTGCAGGACCCTACGGAGCTCGCCCCCCAG
	CAGGTGCCAGGAATAAAGTTCAACATCAGGCCAAGGCAGCCCCACCACGACCTCCCACCAGGCGGCT
	CTGGGGTGCGTTTTCCCGAGTTCGTCCAGTACCTGCTGGACGTGCACCGGCCCGTGGGGATGGACAT
	TCACTGGGACCATGTCAGCCGGCTCTGCAGCCCCTGCCTCATCGACTACGATTTCGTAGGCAAGTTC
	GAGAGCATGGAGGACGATGCCAACTTCTTCCTGAGCCTCATCCGCGCGCCGCGGAACCTGACCTTCC
	CCCGGTTCAAGGACCGGCACTCGCAGGAGGCGCGGACCACAGCGAGGATCGCCCACCAGTACTTCGC
	CCAACTCTCGGCCCTGCAAAGGCAGCGCACCTACGACTTCTACTACATGGATTACCTGATGTTCAAC
	TATTCCAAGCCCTTTACAGATCTGTACTGAGGGGCGCCGC
	ORF Start: ATG at 15		ORF Stop: TGA at 564
	SEQ ID NO: 132	183 aa	MW at 21347.3 kD
NOV30a,	MTLRPGTMRLACMFSSILLFGAAGLLLFISLQDPTELAPQQVPGIKFNIRPRQPHHDLPPGGSGVRF
CG148888-01
Protein Sequence	PEFVQYLLDVHRPVGMDIHWDHVSRLCSPCLIDYDFVGKFESMEDDANFFLSLIRAPRNLTFPRFKD
	RHSQEARTTARIAHQYFAQLSALQRQRTYDFYYMDYLMFNYSKPFTDLY

[0503] Further analysis of the NOV30a protein yielded the following properties shown in Table 30B.

TABLE 30B
Protein Sequence Properties NOV30a
PSort analysis:   0.8650 probability located in lysosome (lumen);
                  0.8200 probability located in outside;
                  0.3657 probability located in microbody (peroxisome);
                  0.1000 probability located in endoplasmic reticulum
                  (membrane)
SignalP analysis: Cleavage site between residues 38 and 39

[0504] A search of the NOV30a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 30C.

TABLE 30C
Geneseq Results for NOV30a
		NOV30a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
ABB53266	Human polypeptide #6 -	62 . . . 183	121/122 (99%)	4e−69
	Homo sapiens, 424 aa.	303 . . . 424	121/122 (99%)
	[WO200181363-AI,
	01-NOV-2001]
ABB53265	Human polypeptide #5 -	62 . . . 183	121/122 (99%)	4e−69
	Homo sapiens, 628 aa.	507 . . . 628	121/122 (99%)
	[WO200181363-A1,
	01-NOV-2001]
AAE15437	Human drug metabolising enzyme	62 . . . 183	121/122 (99%)	4e−69
	(DME)-4 - Homo sapiens, 396 aa.	275 . . . 396	121/122 (99%)
	[WO200179468-A2,
	25-OCT-2001]
AAB85083	Human interleukin-6 (IL-6)	62 . . . 183	121/122 (99%)	4e−69
	like polypeptide - Homo	50 . . . 171	121/122 (99%)
	sapiens, 171 aa.
	[WO200142484-A1,
	14-JUN-2001]
AAM24429	Murine EST encoded protein	62 . . . 183	121/122 (99%)	4e−69
	SEQ ID NO: 1954 - Mus	303 . . . 424	121/122 (99%)
	musculus, 424 aa.
	[WO200154477-A2,
	02-AUG-2001]

[0505] In a BLAST search of public sequence datbases, the NOV30a protein was found to have homology to the proteins shown in the BLASTP data in Table 30D.

TABLE 30D
Public BLASTP Results for NOV30a
		NOV30a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9H3N2	GalNAc 4-sulfotransferase	62 . . . 183	121/122 (99%)	1e−68
	(GalNAc-4-O-sulfotransferase 1)	303 . . . 424	121/122 (99%)
	(Carbohydrate (N-acetylgalactosamine
	4-0) sulfotransferase 8) (Hypothetical
	48.8 kDa protein) - Homo sapiens
	(Human), 424 aa.
Q9H2A9	N-acetylgalactosamine-4-O-	62 . . . 183	120/122 (98%)	4e−68
	sulfotransferase - Homo sapiens	303 . . . 424	120/122 (98%)
	(Human), 424 aa.
Q9BXH4	GalNAc-4-sulfotransferase 2 - Homo	62 . . . 179	77/118 (65%)	1e−44
	sapiens (Human), 443 aa.	325 . . . 442	95/118 (80%)
Q9BXH3	GalNAc-4-sulfotransferase 2 - Homo	62 . . . 179	77/118 (65%)	1e−44
	sapiens (Human), 358 aa.	240 . . . 357	95/118 (80%)
Q9BZW9	N-acetylgalactosamine	62 . . . 179	77/118 (65%)	1e−44
	4-O-sulfotransferase 2 GalNAc4ST-2 -	320 . . . 437	95/118 (80%)
	Homo sapiens (Human), 438 aa.

Example 31

[0506] 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	2325 bp
NOV31a,	CCCAGGCCGGACAAGCGTCCCGAAAGCCCCGGGAGAGACTAAGAAGCAATCCTCCCACGCGCTTTCT
CG149008-01
DNA Sequence	CCCACCCTCGGGCCACTGAGACCGAGGGACAGAGGGCCGCCCTCGCCCCGCCGAGGCCCCGCCTCCC
	GCTCGCCCGCCCGCGCCTCCAGCGGAAGCCGGAAGCAAAAGCGGGTCCTGCTAGCCCCGCGGCTCCG
	AACTCGGTGGTCCTGGAAGCTCCGCAGGATGGGGGAGAAGATGGCGGAAGACGAGAGGTTCCCCAAT
	ACAACTCATGAGGGTTTCAATGTCACCCTCCACACCACCCTGGTTGTCACGACGAAACTGGTGCTCC
	CGACCCCTGGCAAGCCCATCCTCCCCGTGCAGACAGGGGAGCAGGCCCAGCAAGAGGAGCAGTCCAG
	CGGCATGACCATTTTCTTCACCCTCCTTGTCCTAGCTATCTGCATCATATTGGTGCATTTACTGATC
	CGATACAGATTACATTTCTTGCCAGAGAGTGTTGCTGTTGTTTCTTTAGGTATTCTCATGGGAGCAG
	TTATAAAAATTATAGAGTTTAAAAAACTGGCGAATTGGAAGGAAGAAGAAATGTTTCGTCCAAACAT
	GTTTTTCCTCCTCCTGCTTCCCCCTATTATCTTTGAGTCTGGATATTCATTACACAAGGTGAGACTC
	AGGCACACATTGGGTAACTTCTTTCAAAATATTGGTTCCATCACCCTGTTTGCTGTTTTTGGGACGG
	CAATCTCCGCTTTTGTAGTAGGTGGAGGAATTTATTTTCTGGGTCAGGCTGATGTAATCTCTAAACT
	CAACATGACACACAGTTTTGCGTTTGGCTCCCTAATATCTGCTGTCGATCCAGTGGCCACTATTGCC
	ATTTTCAATGCACTTCATGTGGACCCCGTGCTCAACATGCTGGTCTTTGCAGAAAGTATTCTCAACG
	ATGCAGTCTCCATTGTTCTGACCAACACAGCTGAAGGTTTAACAAGAAAAAATATGTCAGATGTCAG
	TGGGTGGCAAACATTTTTACAAGCCCTTGACTACTTCCTCAAAATGTTCTTTGGCTCTGCAGCGCTC
	GGCACTCTCACTGGCTTAATTTCTGCATTAGTGCTGAAGCATATTGACTTGAGGAAAACGCCTTCCT
	TGGAGTTTGGCATGATGATCATTTTTGCTTATCTGCCTTATGGGCTTGCAGAAGGAATCTCACTCTC
	AGGCATCATGGCCATCCTGTTCTCAGGCATCGTGATGTCCCACTACACGCACCATAACCTCTCCCCA
	GTCACCCAGATCCTCATGCAGCAGACCCTCCGCACCGTGGCCTTCTTATGTGAAACATGTGTGTTTG
	CATTTCTTGGCCTGTCCATTTTTAGTTTTCCTCACAAGTTTGAAATTTCCTTTGTCATCTGGTGCAT
	AGTGCTTGTACTATTTGGCAGAGCGGTAAACATTTTCCCTCTTTCCTACCTCCTGAATTTCTTCCGG
	GATCATAAAATCACACCGAAGATGATGTTCATCATGTGGTTTAGTGGCCTGCGGGGAGCCATCCCCT
	ATGCCCTGAGCCTACACCTGGACCTGGAGCCCATGGAGAAGCGGCAGCTCATCGGCACCACCACCAT
	CGTCATCGTGCTCTTCACCATCCTGCTGCTGGGCGGCAGCACCATGCCCCTCATTCGCCTCATGGAC
	ATCGAGGACGCCAAGGCACACCGCAGGAACAAGAAGGACGTCAACCTCAGCAAGACTGAGAAGATGG
	GCAACACTGTGGAGTCGGAGCACCTGTCGGAGCTCACGGAGGAGGAGTACGAGGCCCACTACATCAG
	GCGGCAGGACCTTAAGGGCTTCGTGTGGCTGGACGCCAAGTACCTGAACCCCTTCTTCACTCGGAGG
	CTGACGCAGGAGGACCTGCACCACGGGCGCATCCAGATGAAAACTCTCACCAACAAGTGGTACGAGG
	AGGTACGCCAGGGCCCCTCCCGCTCCGAGGACGACGAGCAGGAGCTCCTCTGACGCCAGGTGCCAAG
	GCTTCAGGCAGGCAGGCCCAGGATGGGCGTTTGCTGCGCACAGACACTCAGCAGGGGCCTCGCAGAC
	ATGCCTGCATCCAGCAGCCCCTTCAAGACATAAGAGGGCGGGGCGAGGTACTGGCTGCACAGTCGCC
	TTAGTCCAGAACCTGACACGCCTCTGGAGCCAGGCGACTTCTTGGGAAACTGTCATCTCCCGACTCC
	TCCCTGAGCCAGCCTCCGCTCAGTGTGGCTCCTCAGCCCACAGAGGGGAGGGAGCATGGGGCCAGGT
	GCCAGTCATCTGTGAAGCTAGGGCGCCTACCCCCCCACCCGGAGGAC
	ORF Start: ATG at 230		ORF Stop: TGA at 1994
	SEQ ID NO: 134	588 aa	MW at 66297.1 kD
NOV31a,	MGEKMAEEERFPNTTHEGFNVTLHTTLVVTTKLVLPTPGKPILPVQTGEQAQQEEQSSGMTIFFSLL
CG149008-01
Protein Sequence	VLAICIILVHLLIRYRLHFLPESVAVVSLCILMGAVIKIIEFKKLANWKEEEMFRPNMFFLLLLPPT
	IFESGYSLHKVRLRHTLCNFFQNIGSTTLFAVFGTAISAFVVGGGIYFLGQADVTSKLNMTDSFAFG
	SLISAVDPVATIAIFNALHVDPVLNMLVFGESILNDAVSIVLTNTAEGLTRKNMSDVSGWQTFLQAL
	DYFLKMFFGSAALGTLTGLISALVLKHIDLRKTPSLEFGMMIIFAYLPYGLAEGISLSGIMAILFSG
	IVMSHYTHHNLSPVTQILMQQTLRTVAFLCETCVFAFLGLSIFSFPHRFETSFVIWCIVLVLFGRAV
	NIFPLSYLLNFFRDHKITPKMMFIMWFSGLRGAIPYALSLHLDLEPMEKRQLIGTTTIVIVLFTILL
	LGGSTMPLIRLMDIEDAXAHRRNKKDVNLSKTEKMGNTVESEHLSELTEEEYEAHYIRRQDLKGFVW
	LDAKYLNPFFTRRLTQEDLHMGRIQMKTLTNKWYEEVRQGPSGSEDDEQELL

[0507] Further analysis of the NOV31a protein yielded the following properties shown in Table 31B.

TABLE 31B
Protein Sequence Properties NOV31a
PSort analysis:   0.8000 probability located in plasma membrane;
                  0.4000 probability located in Golgi body;
                  0.3000 probability located in endoplasmic
                  reticulum (membrane); 0.3000 probability located in
                  microbody (peroxisome)
SignalP analysis: Cleavage site between residues 40 and 41

[0508] A search of the NOV31a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 31C.

TABLE 31C
Geneseq Results for NOV31a
		NOV31a
		Residues/	Identities/
Geneseq	Protein/Organism/Length	Match	Similarities for the	Expect
Identifier	[Patent #, Date]	Residues	Matched Region	Value
ABG61535	Human transporter and ion	1 . . . 588	581/588 (98%)	0.0
	channel, TRICH5, Incyte ID	91 . . . 671	581/588 (98%)
	7476938CD1 - Homo
	sapiens, 671 aa.
	[WO200240541-A2,
	23-MAY-2002]
AAM24062	Human EST encoded protein	274 . . . 588	315/315 (100%)	0.0
	SEQ ID NO: 1587 - Homo	1 . . . 315	315/315 (100%)
	sapiens, 315 aa.
	[WO200154477-A2,
	02-AUG-2001]
AAB29621	Cat flea HMT Na/H	8 . . . 584	329/585 (56%)	e−175
	transporter, SEQ ID	33 . . . 602	416/585 (70%)
	NO: 1868 - Ctenocephalides
	felis, 608 aa.
	[WO200061621-A2,
	19-OCT-2000]
ABB59364	Drosophila melanogaster	44 . . . 587	310/562 (55%)	e−170
	polypeptide SEQ ID NO	86 . . . 635	399/562 (70%)
	4884 - Drosophila
	melanogaster, 649 aa.
	[WO200171042-A2,
	27-SEP-2001]
AA014196	Human transporter and ion	117 . . . 547	166/439 (37%)	2e−72
	channel TRICH-13 - Homo	125 . . . 542	253/439 (56%)
	sapiens, 631 aa.
	[WO200204520-A2,
	17-JAN-2002]

[0509] In a BLAST search of public sequence datbases, the NOV31 a 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
Protein		Residues/	Identities/
Accession		Match	Similarities for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
BAA76783	KIAA0939 protein - Homo	1 . . . 588	581/588 (98%)	0.0
	sapiens (Human), 595 aa	15 . . . 595	581/588 (98%)
	(fragment).
Q8R4D1	Na—H exchanger isoform	5 . . . 587	556/583 (95%)	0.0
	NHE8 - Mus musculus	1 . . . 575	565/583 (96%)
	(Mouse), 576 aa.
Q9Y507	DJ963K23.4 (Continues in	152 . . . 588	437/437 (100%)	0.0
	dJ1041C10 (AL162615)) -	1 . . . 437	437/437 (100%)
	Homo sapiens (Human), 437
	aa (fragment).
Q9Y2E8	KIAA0939 protein - Homo	182 . . . 588	405/407 (99%)	0.0
	sapiens (Human), 411 aa	5 . . . 411	406/407 (99%)
	(fragment).
AAH34508	Hypothetical protein - Mus	209 . . . 587	366/379 (96%)	0.0
	musculus (Mouse), 388 aa	9 . . . 387	374/379 (98%)
	(fragment).

[0510] PFam analysis predicts that the NOV31a protein contains the domains shown in the Table 31E.

TABLE 31E
Domain Analysis of NOV31a
		Identities/
	NOV31a	Similarities
	Match	for the Matched	Expect
Pfam Domain	Region	Region	Value
Na_H_Exchanger	62 . . . 485	141/465 (30%)	3.1e−98
		345/465 (74%)

Example 32

[0511] 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	367 bp
NOV32a,	ATGGCGGGGAGAAGGAAGCTCATCGCAGTGATCAGAGACAAGGACACGGTGACTGGTTTCCTGCTGG
CG149350-01
DNA Sequence	GCAGCATAGGGGAGCTTAACAAGAACTGCCACCCCAATTTCCTGGTGGTGGAGAAGGATACGACCAT
	CAATGAGATCGAAGACACTTTCCGGCAATTTCTAAACCGGGATGACACTGGCATCATCCTCATCAAC
	CAGTACATCGCAGAGATGGTGCAGCATGCCCTGGACACCCACCAGCACTCTATCCCTACTGTCCTGG
	AGATCCCCTCCAAGGAGCACCCATATGAGGACGCCAAGGACTCCACCCTGCGGAGGGCCAGGGGCAT
	GTTCACTGCCGAAGACCTGTGCTAGGGTCTTT
	ORF Start: ATG at 1		ORF Stop: TAG at 358
	SEQ ID NO: 136	119 aa	MW at 13566.3 kD
NOV32a,	MAGRRKLIAVIRDKDTVTGFLLGSIGELNXNCHFNFLVVEKDTTINEIEDTFRQFLNRDDTGIILIN
CG149350-01
Protein Sequence	QYIAEMVQHALDTHQHSIPTVLEIPSKEHPYEDAKDSTLRRARGMFTAEDLC
	SEQ ID NO: 137	367 bp
NOV32b,	ATGGCGGGGAGAAGGAAGCTCATCGCAGTGATCAGAGACAAGGACACGGTGACTCGTTTCCTGCTGG
CG149350-02
DNA Sequence	GCAGCATAGGGGAGCTTAACAAGAACTGCCACCCCAATTTCCTGGTGGTGGAGAAGGATACGACCAT
	CAATGAGATCGAAGACACTTTCCGGCAATTTCTAAACCGGGATGACACTGGCATCATCCTCATCAAC
	CAGTACATCGCAGAGATGGTGCAGCATGCCCTGGACACCCACCAGCACTCTATCCCTACTGTCCTGG
	AGATCCCCTCCAAGGAGCACCCATATGAGGACGCCAAGGACTCCACCCTGCGGAGGGCCAGGGGCAT
	GTTCACTGCCGAAGACCTGTGCTAGGGTCTTT
	ORF Start: ATG at 1		ORF Stop: TAG at 358
	SEQ ID NO: 138	119 aa	MW at 13566.3 kD
NOV32b,	MAGRRKLIAVIRDKDTVTGFLLGSIGELNKNCHPNFLVVEKDTTINEIEDTFRQFLNRDDTGIILIN
CG149350-02
Protein Sequence	QYIAEMVQHALDTHQHSIPTVLEIPSKEHPYEDAKDSTLRRARGMFTAEDLC

[0512] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 32B.

TABLE 32B
Comparison of NOV32a against NOV32b.
			Identities/
		NOV32a Residues/	Similarities for
	Protein Sequence	Match Residues	the Matched Region
	NOV32b	1 . . . 119	119/119 (100%)
		1 . . . 119	119/119 (100%)

[0513] Further analysis of the NOV32a protein yielded the following properties shown in Table 32C.

TABLE 32C
Protein Sequence Properties NOV32a
PSort analysis:   0.4852 probability located in mitochondrial matrix
                  space; 0.4500 probability located in cytoplasm;
                  0.1957 probability located in mitochondrial inner
                  membrane; 0.1957 probability located in
                  mitochondrial intermembrane space
SignalP analysis: No Known Signal Sequence Predicted

[0514] 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
AAW27337	Human vacuolar ATPase 14	1 . . . 118	105/118 (88%)	2e−54
	kDa subunit hV-14B - Homo	1 . . . 118	108/118 (90%)
	sapiens, 119 aa.
	[JP09168390-A,
	30-JUN-1997]
AAW27336	Human vacuolar ATPase 14	1 . . . 118	104/118 (88%)	8e−54
	kDa subunit hV-14A - Homo	1 . . . 118	107/118 (90%)
	sapiens, 119 aa.
	[JP09168390-A,
	30-JUN-1997]
ABB62928	Drosophila melanogaster	6 . . . 118	71/113 (62%)	2e−38
	polypeptide SEQ ID NO	10 . . . 122	91/113 (79%)
	15576 - Drosophila
	melanogaster, 124 aa.
	[WO200171042-A2,
	27-SEP-2001]
ABB57798	Drosophila melanogaster	6 . . . 114	58/109 (53%)	7e−29
	polypeptide SEQ ID NO 186 -	10 . . . 118	84/109 (76%)
	Drosophila melanogaster,
	124 aa. [WO200171042-A2,
	27-SEP-2001]
AAG35989	Zea mays protein fragment	1 . . . 118	56/125 (44%)	1e−27
	SEQ ID NO: 44042 - Zea	1 . . . 125	85/125 (67%)
	mays subsp. mays, 130 aa.
	[EP1033405-A2,
	06-SEP-2000]

[0515] 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
Number	Protein/Organism/Length	Residues	Portion	Expect Value
P50408	Vacuolar ATP synthase	1 . . . 118	104/118 (88%)	1e−53
	sunit F (EC 3.6.3.14)	1 . . . 118	108/118 (91%)
	(V-ATPase F subunit)
	(Vacuolar proton pump F
	subunit) (V-ATPase 14 kDa
	subunit) - Rattus norvegicus
	(Rat), 119 aa.
Q16864	Vacuolar ATP synthase	1 . . . 118	104/118 (88%)	2e−53
	subunit F(EC 3.6.3.14)	1 . . . 118	107/118 (90%)
	(V-ATPase F subunit)
	(Vacuolar proton pump F
	subunit)(V-ATPase 14 kDa
	subunit) - Homo sapiens
	(Human), 119 aa.
Q9D1K2	1110004G16Rik protein-	1 . . . 118	103/118 (87%)	5e−53
	Mus musculus (Mouse), 119	1 . . . 118	108/118 (91%)
	aa.
Q28029	Vacuolar ATP synthase	10 . . . 118	97/109 (88%)	7e−50
	subunit F (EC 3.6.3.14)	1 . . . 109	100/109 (90%)
	(V-ATPase F subunit)
	(Vacuolar proton pump F
	subunit) (V-ATPase 14 kDa
	subunit) - Bos taurus
	(Bovine), 110 aa (fragment).
Q9I8H3	Vacuolar ATP synthase	10 . . . 118	83/109 (76%)	7e−43
	subunit F (EC 3.6.3.14)	1 . . . 109	94/109 (86%)
	(V-ATPase F subunit)
	(Vacuolar proton pump F
	subunit) (V-ATPase 14 kDa
	subunit) - Xenopus laevis
	(African clawed frog), 110 aa
	(fragment).

[0516] PFam analysis predicts that the NOV32a protein contains the domains shown in the Table 32F.

TABLE 32F
Domain Analysis of NOV32a
		Identities/
		Similarities
		for the Matched	Expect
Pfam Domain	NOV32a Match Region	Region	Value
ATP-synt_F	8 . . . 108	51/107 (48%)	9.2e−43
		90/107 (84%)

Example 33

[0517] 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	1510 bp
NOV33a,	ATGGGTTCAGACTTTATGCCCTGAAAAGATCCTTCCAGCCCTGGCCATCTTGGACTTCTGGAGCTAC
CG149463-01
DNA Sequence	CCTGGCTCACAGGGGTCTTGTTGCCCTGGGTGTCCCCAGTTCTTGAAAAGAATCACCCTGGGAGGGC
	CCACACCCTGACCATCCCCCTTTATCCCTTCTGAGATGTTTGTTAGGAAGTCTGGGTCCAGGCGATA
	TCATTTCTTGTTCCATCCATGCAGGGGTTGCTTACCTCGGGTAGGAAACCCTCAGGCGGTGGCAGGT
	GCACAGGTAGGGGAGGATGGAGAGGGCAGTCGTGCCTGAAGCCCTGGATGGGCGGAGCTGACCCCCC
	AACACCAACTCTATCATGCCTGCTCCTCCCTGTCCCCCCAGAGCTGCCTGATCATTGCTACAGAATG
	AACTCTAGCCCAGCTGGGACCCCAAGTCCACAGCCCTCCAGGGCCAATGGGAACATCAACCTGGGGC
	CTTCAGCCAACCCAAATGCCCAGCCCACGGACTTCGACTTCCTCAAAGTCATCGGCAAAGGGAACTA
	CGGGAAGGTCCTACTGGCCAAGCGCAAGTCTGATGGGGCGTTCTATGCAGTGAAGGTACTACAGAAA
	AAGTCCATCTTAAACAAGAAAGAGCAGAGCCACATCATGGCAGAGCGCAGTGTGCTTCTGAAGAACG
	TGCGGCACCCCTTCCTCGTGGGCCTGCGCTACTCCTTCCAGACACCTGAGAAGCTCTACTTCGTGCT
	CGACTATGTCAACGGGGGAGAGCTCTTCTTCCACCTGCAGCGGGAGCGCCGGTTCCTGGAGCCCCGG
	GCCAGGTTCTACGCTGCTGAGGTGGCCAGCGCCATTGGCTACCTGCACTCCCTCAACATCATTTACA
	GGGATCTGAAACCAGAGAACATTCTCTTGGACTGCCAGTACTTGGCACCTGAAGTGCTTCGGAAAGA
	GCCTTATGATCGAGCAGTGGACTGGTGGTGCTTGGGGGCAGTCCTCTACGAGATGCTCCATGGCCTG
	CCGCCCTTCTACAGCCAAGATGTATCCCAGATGTATGAGAACATTCTGCACCAGCCGCTACAGATCC
	CCGGAGGCCGGACAGTGGCCGCCTGTGACCTCCTGCAAAGCCTTCTCCACAAGGACCAGAGGCAGCG
	GCTGGGCTCCAAAGCAGACTTTCTTGAGATTAAGAACCATGTATTCTTCAGCCCCATAAACTGGGAT
	GACCTGTACCACAAGAGCCTAACTCCACCCTTCAACCCAAATGTGACAGGACCTGCTGACTTGAAGC
	ATTTTGACCCAGAGTTCACCCAGGAAGCTGTGTCCAAGTCCATTGGCTGTACCCCCGACACTGTGGC
	CAGCAGCTCTGCCGCCTCAAGTGCATTCCTCGGATTTTCTTATGCGCCAGAGGATGATGACATCTTG
	GATTGTTAGAAGAGAAGGGCCTGTGAAACTACTGAGCCCAGCTGGTATTAGTAAGGAATTACCTTCA
	GCTGCTAGGAAGAGCGACTCAAACTAACAATGGCTT
	ORF Start: ATG at 220		ORF Stop: TAG at 1414
	SEQ ID NO 140	398 aa	MW at 44552.5 kD
NOV33a,	MQGLLTSGRKPSGGGRCTGRGGWRGQWCLKPWMCGADPPTPTLSCLLLPVPPELPDHCYRNNSSPAG
CG149463-01
Protein Sequence	TPSPQPSRANGNINLGPSANPNAQPTDFDFLKVIGKGNYGKVLLAKRKSDGAFYAVKVLQKKSILKR
	KEQSHIMAERSVLLKNVRHPFLVGLRYSFQTPEKLYFVLDYVNGGELFFHLQRERRFLEPRARFYAA
	EVASAIGYLHSLNIIYRDLKPENILLDCQYLAPEVLRKEFYDRAVDWWCLGAVLYEMLHGLPPFYSQ
	DVSQMYENILHQPLQIPGGRTVAACDLLQSLLHKDQRQRLGSKADFLEIKNHVFFSPINWDDLYHKR
	LTPPFNPNVTGPADLKHFDPEFTQEAVSKSIGCTPDTVASSSGASSAFLGFSYAPEDDDILDC

[0518] Further analysis of the NOV33a protein yielded the following properties shown in Table 33B.

TABLE 33B
Protein Sequence Properties NOV33a
PSort analysis:   0.4500 probability located in cytoplasm;
                  0.2677 probability located in microbody (peroxisome);
                  0.1859 probability located in lysosome (lumen);
                  0.1000 probability located in mitochondrial
                  matrix space
SignalP analysis: No Known Signal Sequence Predicted

[0519] 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
Identifier	[Patent #, Date]	Residues	Region	Expect Value
AAY95276	Human serum and	1 . . . 398	398/427 (93%)	0.0
	glucocorticoid-induced	1 . . . 427	398/427 (93%)
	protein kinase 2-beta - Homo
	sapiens, 427 aa.
	[WO200035946-A1,
	22-JUN-2000]
AAM25594	Human protein sequence	53 . . . 398	346/375 (92%)	0.0
	SEQ ID NO: 1109 - Homo	8 . . . 382	346/375 (92%)
	sapiens, 382 aa.
	[WO200153455-A2,
	26-JUL-2001]
AAE22765	Human serum and	61 . . . 398	338/367 (92%)	0.0
	glucocoticoid-induced	1 . . . 367	338/367 (92%)
	protein kinase, SGK2-alpha -
	Homo sapiens, 367 aa.
	[WO200224947-A2,
	28-MAR-2002]
AAB65708	Novel protein kinase, SEQ	61 . . . 398	337/367 (91%)	0.0
	ID NO: 237 - Homo sapiens,	1 . . . 367	338/367 (91%)
	367 aa. [WO200073469-A2,
	07-DEC-2000]
AAB65615	Novel protein kinase, SEQ	184 . . . 398	215/244 (88%)	e−122
	ID NO: 141 - Mus musculus,	1 . . . 244	215/244 (88%)
	244 aa. [WO200073469-A2,
	07-DEC-2000]

[0520] 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
Number	Protein/Organism/Length	Residues	Portion	Expect Value
Q9HBY8	Protein kinase - Homo sapiens	1 . . . 398	398/427 (93%)	0.0
	(Human), 427 aa.	1 . . . 427	398/427 (93%)
Q9UKG6	Protein kinase (DJ138B7.2)	61 . . . 398	338/367 (92%)	0.0
	(Serum/glucocorticoid	1 . . . 367	338/367 (92%)
	regulated kinase 2) (Similar to
	serum/glucocorticoid
	regulated kinase 2) - Homo
	sapiens (Human), 367 aa.
Q8R0P6	Serum/glucocorticoid	61 . . . 397	317/366 (86%)	0.0
	regulated kinase 2 - Mus	1 . . . 365	326/366 (88%)
	musculus (Mouse), 366 aa.
O73927	S-sgk2 - Squalus acanthias	70 . . . 396	235/359 (65%)	e−133
	(Spiny dogfish), 594 aa.	236 . . . 594	277/359 (76%)
O73926	S-sgk1 - Squalus acanthias	61 . . . 396	239/374 (63%)	e−132
	(Spiny dogfish), 433 aa.	60 . . . 433	282/374 (74%)

[0521] PFam analysis predicts that the NOV33a protein contains the domains shown in the Table 33E.

TABLE 33E
Domain Analysis of NOV33a
		Identities/
Pfam	NOV33a	Similarities	Expect
Domain	Match Region	for the Matched Region	Value
pkinase	95 . . . 228	54/135 (40%)	5e−39
		116/135 (86%)
pkinase	231 . . . 323	35/128 (27%)	1.5e−21
		69/128 (54%)
pkinase13C	324 . . . 393	25/73 (34%)	3.1e−15
		47/73 (64%)

Example 34

[0522] 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	2152 bp
NOV34a,	GGGGGGCCTGAGCCTCTCCGCCGGCGCAGGCTCTGCTCGCGCCAGCTCGCTCCCGCAGCCATGCCCA
CG149536-01
DNA Sequence	CCACCATCGAGCGGGAGTTCGAAGAGTTGGATACTCAGCGTCCCTGGCAGCCGCTGTACTTGGAAAT
	TCGAAATGAGTCCCATGACTATCCTCATAGAGTGGCCAAGTTTCCAGAAAACAGAAATCGAAACAGA
	TACAGAGATGTAAGCCCATATGATCACAGTCGTGTTAAACTGCAAAATGCTGAGAATGATTATATTA
	ATGCCAGTTTAGTTGACATAGAAGAGGCACAAAGGAGTTACATCTTAACACAGGGACCACTTCCTAA
	CACATGCTGCCATTTCTGGCTTATGGTTTGGCAGCAGAAGACCAAAGCAGTTGTCATGCTGAACCGC
	ATTGTGGAGAGAGAATCGAGTGGTGAAACCAGAACAATATCTCACTTTCATTATACTACCTGGCCAG
	ATTTTGGAGTCCCTGAATCACCAGCTTCATTTCTCAATTTCTTGTTTAAAGTGAGAGAATCTGGCTC
	CTTGAACCCTCACCATGGGCCTGCGGTGATCCACTGTAGTGCAGGCATTGGGCGCTCTGGCACCTTC
	TCTCTGGTAGACACTTGTCTTGTTTTGATCGAAAAAGGAGATGATATTAACATAAAACAAGTGTTAC
	TGAACATGAGAAAATACCGAATGGGTCTTATTCAGACCCCAGATCAACTGAGATTCTCATACATGGC
	TATAATAGAAGGAGCAAAATGTATAAAGGGAGATTCTAGTATACAGAAACGATGGAAAGAACTTTCT
	AAGGAAGACTTATCTCCTGCCTTTGATCATTCACCAAACAAAATAATGACTGAAAAATACAATGGGA
	ACAGAATAGGTCTAGAAGAAGAAAAACTGACAGGTGACCGATGTACACGACTTTCCTCTAAAATGCA
	AGATACAATGGAGGAGAACAGTGAGAGTGCTCTACGGAAACGTATTCGAGAGGACAGAAAGGCCACC
	ACAGCTCAGAAGGTGCAGCAGATGAAACAGAGGCTAAATGAGAATGAACCAGAAAAAGAAAAGTGGT
	TATATTGGCAACCTATTCTCACTAAGATGGGGTTTATGTCAGTCATTTTCGTTGGCGCTTTTGTTGG
	CTGGAGACTGTTTTTTCAGCAAAATGCCCTATAAACAATTAATTTTGCCCAGCAAGCTTCTGCACTA
	GTAACTGACAGTGCTACATTAATCATAGGGGTTTGTCTGCAGCAAACGCCTCATATCCCAAAAACGC
	TGCAGTAGAATAGACATCAACCAGATAAGTGATATTTACAGTCACAAGCCCAACATCTCAGGACTCT
	TGACTGCAGGTTCCTCTGAACCCCAAACTGTAAATGGCTGTCTAAAATAAAGACATTCATGTTTGTT
	AAAAACTGGTAAATTTTGCAACTGTATTCATACATGTCAAACACAGTATTTCACCTGACCAACATTG
	AGATATCCTTTATCACAGGATTTGTTTTTGGAGGCTATCTGGATTTTAACCTGCACTTGATATAAGC
	AATAAATATTGTGGTTTTATCTACGTTATTGGAAAGAAAATGACATTTAAATAATGTGTGTAATGTA
	TAATGTACTATTGACATGGGCATCAACACTTTTATTCTTAAGCATTTCAGGGTAAATATATTTTATA
	AGTATCTATTTAATCTTTTGTAGTTAACTGTACTTTTTAAGAGCTCAATTTGAAAAATCTGTTACTA
	AAAAAAAAAATTGTATGTCGATTGAATTGTACTGGATACATTTTCCATTTTTCTAAAAAGAAGTTTG
	ATATGAGCAGTTAGAAGTTGGAATAAGCAATTTCTACTATATATTGCATTTCTTTTATGTTTTACAC
	TTTTCCCCATTTTAAAAAGAAAAGCAAACAAAGAAACAAAAGTTTTTCCTAAAAATATCTTTGAAGG
	AAAATTCTCCTTACTGGGATAGTCAGGTAAACAGTTGGTCAAGACTTTGTAAAGAAATTGGTTTCTG
	TAAATCCCATTATTGATATGTTTATTTTTCATGAAAATTTCAATGTAGTTGGGGTAGATTATGATTT
	AGGAAGCAAAAGTAAGAAGCAGCATTTTATGATTCATAATTTCAGTTTACTACACTGAAGTTTTGAA
	GTAAACCC
	ORF Start: ATG at 61		ORF Stop: TAA at 1171
	SEQ ID NO: 142	370 aa	MW at 43248.9 kD
NOV34a,	MPTTIEREFEELDTQRRWQPLYLEIRNESHDYPHRVAKFPENRNRNRYRDVSPYDHSRVKLQNAEND
CG149536-01
Protein Sequence	YINASLVDIEEAQRSYILTQGPLPNTCCHFWLMVWQQKTKAVVMLNRIVERESSGETRTISHFHYTT
	WPDFGVPESPASFLNFLFKVRESGSLNPDHGPAVIHCSAGIGRSGTFSLVDTCLVLMEKGDDINIKQ
	VLLNMRKYRMGLIQTPDQLRFSYMAIIEGAKCIKGDSSIQKRWKELSKEDLSPAFDHSPNKIMTEKY
	NGNRIGLEEEKLTGDRCTGLSSKMQDTMEENSESALRKRIREDRKATTAQKVQQMKQRLNENERKRK
	RWLYWQPILTKMGFMSVILVGAFVGWRLFFQQNAL

[0523] Further analysis of the NOV34a protein yielded the following properties shown in Table 34B.

TABLE 34B
Protein Sequence Properties NOV34a
PSort analysis:   0.8500 probability located in endoplasmic
                  reticulum (membrane); 0.4400 probability located in
                  plasma membrane; 0.3000 probability located in
                  nucleus; 0.1000 probability located in mitochondrial
                  inner membrane
SignalP analysis: No Known Signal Sequence Predicted

[0524] A search of the NOV34a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 34C.

TABLE 34C
Geneseq Results for NOV34a
		NOV34a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAR14114	Non-receptor linked protein	1 . . . 370	368/415 (88%)	0.0
	tyrosine phosphatase - Homo	1 . . . 415	369/415 (88%)
	sapiens, 415 aa.
	[WO9113989-A,
	19-SEP-1991]
AAU91293	Human NOV8 protein -	1 . . . 370	337/415 (81%)	0.0
	Homo sapiens, 415 aa.	1 . . . 415	345/415 (82%)
	[WO200216600-A2,
	28-FEB-2002]
ABP41882	Human ovarian antigen	24 . . . 336	312/358 (87%)	e−178
	HOCPJ87, SEQ ID NO:3014 -	5 . . . 362	313/358 (87%)
	Homo sapiens, 368 aa.
	[WO200200677-A 1,
	03-JAN-2002]
AAM25250	Human protein sequence	116 . . . 269	137/154 (88%)	1e−77
	SEQ ID NO:765 - Homo	14 . . . 167	145/154 (93%)
	sapiens, 168 aa.
	[WO200153455-A2,
	26-JUL-2001]
AAB56662	Human prostate cancer	1 . . . 124	123/124 (99%)	1e−69
	antigen protein sequence	29 . . . 152	124/124 (99%)
	SEQ ID NO:1240 - Homo
	sapiens, 180 aa.
	[WO200055174-A1,
	21-SEP-2000]

[0525] In a BLAST search of public sequence datbases, the NOV34a protein was found to have homology to the proteins shown in the BLASTP data in Table 34D.

TABLE 34D
Public BLASTP Results for NOV34a
		NOV34a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched
Number	Protein/Organism/Length	Residues	Portion	Expect Value
P17706	Protein-tyrosine phosphatase,	1 . . . 370	369/415 (88%)	0.0
	non-receptor type 2 (EC	1 . . . 415	370/415 (88%)
	3.1.3.48) (T - cell
	protein-tyrosine phosphatase)
	(TCPTP) - Homo sapiens
	(Human), 415 aa.
A33899	protein-tyrosine-phosphatase	1 . . . 370	368/415 (88%)	0.0
	(EC 3.1.3.48), nonreceptor type	1 . . . 415	369/415 (88%)
	2 - human, 415 aa.
A60345	protein-tyrosine-phosphatase	1 . . . 336	334/381 (87%)	0.0
	(EC 3.1.3.48) 11A - human,	1 . . . 381	335/381 (87%)
	387 aa.
Q922E7	Protein tyrosine phosphatase,	1 . . . 365	323/410 (78%)	0.0
	non-receptor type 2 - Mus	1 . . . 405	338/410 (81%)
	musculus (Mouse), 406 aa.
Q06180	Protein-tyrosine phosphatase,	l . . . 336	298/381 (78%)	e−168
	non-receptor type 2 (EC	1 . . . 376	312/381 (81%)
	3.1.3.48) (Protein-tyrosine
	phosphatase PTP-2)(MPTP) -
	Mus musculus (Mouse), 382
	aa.

[0526] PFam analysis predicts that the NOV34a protein contains the domains shown in the Table 34E.

TABLE 34E
Domain Analysis of NOV34a
		Identities/
		Similarities
		for the Matched	Expect
Pfam Domain	NOV34a Match Region	Region	Value
Y13phosphatase	42 . . . 229	99/272 (36%)	5.5e−88
		163/272 (60%)

Example 35

[0527] 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: 143	908 bp
NOV35a,	CCCTTCTACCCAGAGGGTGAATGGGTATCTTTCCCGGAATAATCCTAATTTTTCTAAGGGTGAAGTT
CG149964-01
DNA Sequence	TGCAACCGCGGCCGTGACTGTAAGCGGACACCAGAAAAGTACCACTGTAAGTCATGAGATGTCTGGT
	CTGAATTGGAAACCCTTTGTATATGGCGGCCTTGCCTCTATCGTGGCTGAGTTTGGGACTTTCCCTG
	TGGACCTTACCAAAACACGACTTCAGGTTCAAGGCCAAAGCATTGATGCCCGTTTCAAAGAGATAAA
	ATATAGAGGCATGTTCCATGCGCTGTTTCGCATCTGTAAAGAGGAAGGTGTATTGGCTCTCTATTCA
	GGAATTGCTCCTGCGTTGCTAAGACAAGCATCATATGGCACCATTAAAATTGGGATTTACCAAAGCT
	TGAAGCGCTTATTCGTAGAACGTTTAGAAGATGAAACTCTTTTAATTAATATGATCTGTGGGGTAGT
	GTCAGGAGTGATATCTTCCACTATAGCCAATCCCACCCATGTTCTAAAGATTCGAATGCAGGCTCAA
	GGAAGCTTGTTCCAAGGGAGCATGATTGGAAGCTTTATCGATATATACCAACAAGAAGGCACCAGGG
	GTCTGTGGAGGGGTGTGGTTCCAACTGCTCACCGTGCTGCCATCGTTGTAGGAGTAGAGCTACCAGT
	CTATGATATTACTAAGAAGCATTTAATATTGTCAGGAATGATGGGACATGTGGATCTCTATAAGGGC
	ACTGTTGATGGTATTTTAAACATGTGGAAACATGAGGGCTTTTTTGCACTCTATAAAGGATTTTGGC
	CAAACTGGCTTCGGCTTGGACCCTGGAACATCATTTTTTTTATTACATACGACCAGGTAAAGAGGCT
	TCAAATCTAAGAACTGAATTATATGTGAGCCCAGCAC
	ORF Start: ATG at 21		ORF Stop: TAA at 879
	SEQ ID NO: 144	286 aa	MW at 32043.5 kD
NOV35a,	MGIFPGIILIFLRVKFATAAVTVSGHQKSTTVSHEMSGLNWKPFVYGGLASIVAEFGTFPVDLTKTR
CG149964-01
Protein Sequence	LQVQGQSIDARFKEIKYRGMFHALFRICKEEGVLALYSGIAPALLRQASYGTIKIGIYQSLKRLFVE
Protein Sequence
	RLEDETLLINMICGVVSGVISSTIANPTDVLKIRMQAQCSLFQGSMIGSFIDIYQQEGTRGLWRGVV
	PTAQRAATVVGVELPVYDITKKHLILSGMMGHVDLYKGTVDGILKMWKHEGFFALYKGFWPNWLRLG
	PWNIIFFITYEQVKRLQI
	SEQ ID NO: 145	871 bp
NOV35b,	CACCGGATCCACCATGGGTATCTTTCCCGGAATAATCCTAATTTTTCTAAGGGTGAAGTTTGCAACG
309326356 DNA
Sequence	GCGGCCGTGATTCACCAGAAAAGTACCACTGTAAGTCATGAGATGTCTGGTCTGAATTGGAAACCCT
Sequence
	TTGTATATGGCGGCCTTGCCTCTATCGTGGCTGAGTTTGGGACTTTCCCTGTGGACCTTACCAAAAC
	ACGACTTCAGGTTCAAGCCCAAAGCATTGATGCCCGTTTCAAAGAGATAAAATATAGAGGGATGTTC
	CATGCGCTGTTTCGCATCTGTAAAGACGAAGGTGTATTCGCTCTCTATTCAGGAATTGCTCCTGCGT
	TGCTAAGACAAGCATCATATGGCACCATTAAAATTGGGATTTACCAAAGCTTGAAGCGCTTATTCGT
	AGAACGTTTAGAAGATGAAACTCTTTTAATTAATATGATCTGTGGGGTAGTGTCAGGAGTGATATCT
	TCCACTATAGCCAATCCCACCGATGTTCTAAAGATTCGAATGCAGGCTCAAGGAAGCTTGTTCCAAG
	GGAGCATGATTCGAAGCTTTATCGATATATACCAACAAGAAGGCACCAGGGGTCTGTGGAGGGGTGT
	GGTTCCAACTGCTCAGCGTGCTCCCATCGTTGTAGGAGTAGAGCTACCAGTCTATGATATTACTAAG
	AACCATTTAATATTGTCAGGAATGATGGGACATGTGGATCTCTATAAGGGCACTGTTGATGGTATTT
	TAAAGATGTGGAAACATGAGGGCTTTTTTGCACTCTATAAAGGATTTTGGCCAAACTGGCTTCGGCT
	TGGACCCTGGAACATCATTTTTTTTATTACATACGAGCAGGTAAAGAGGCTTCAAATCGTCGACGGC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO:146	290 aa	MW at 32429.9 kD
NOV35b,	TGSTMGIFPGIILIFLRVKFATAAVIHQKSTTVSHEMSGLNWKPFVYGGLASTVAEFGTFPVDLTKT
309326356
Protein Sequence	RLQVQGQSIDARFKEIKYRGMFHALFRICKEEGVLALYSGIAPALLRQASYGTIKIGIYQSLKRLFV
	ERLEDETLLINMICCVVSGVISSTIANPTDVLKIRMQAQGSLFQGSMIGSFIDIYQQEGTRGLWRGV
	VPTAQRAAIVVGVELPVYDITKKHLILSGMMGHVDLYKGTVDGILKMWKHEGFFALYKGFWPNWLRL
	GPWNIIFFITYEQVKRLQIVDG
	SEQ ID NO: 147	811 bp
NOV35c,	CACCGGATCCGCCGTGATTCACCAGAAAAGTACCACTGTAAGTCATGAGATGTCTGGTCTGAATTGG
309326444 DNA
Sequence	AAACCCTTTCTATATGGCGGCCTTGCCTCTATCGTGGCTGAGTTTGGGACTTTCCCTGTGGACCTTA
	CCAAAACACCACTTCAGGTTCAAGGCCAAAGCATTGATGCCCGTTTCAAAGAGATAAAATATAGAGG
	GATGTTCCATGCGCTGTTTCGCATCTGTAAAGAGGAAGGTGTATTGGCTCTCTATTCAGGAATTGCT
	CCTGCGTTGCTAAGACAAGCATCATATGGCACCATTAAAATTGGGATTTACCAAAGCTTGAAGCGCT
	TATTCGTAGAACGTTTAGAAGATGAAACTCTTTTAATTAATATGATCTGTGGGGTAGTCTCAGGAGT
	GATATCTTCCACTATAGCCAATCCCACCGATGTTCTAAGATTCGAATGCAGGCTCAAGGAAGCCTTG
	TTCCAAGGGAGCATGATTGGAAGCTTTATCGATATATACCAACAAGAAGGCACCAGGGGTCTGTGGA
	GGGGTGTGGTTCCAACTGCTCAGCGTGCTGCCATCGTTGTAGGAGTAGAGCTACCAGTCTATGATAT
	TACTAAGAAGCATTTAATATTGTCAGGAATGATGGGACATGTGGATCTCTATAAGGGCACTGTTGAT
	GGTATTTTAAAGATGTGGAAACATGAGGGCTTTTTTGCACTCTATAAAGGATTTTGGCCAAACTGGC
	TTCGGCTTGGACCCTGGAACATCATTTTTTTTATTACATACGAGCAGGTAAAGAGGCTTCAAATCGT
	CGACGGC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO: 148	270 aa	MW at 30239.1 kD
NOV35c,	TGSAVIHQKSTTVSHEMSGLNWKPFVYGGLASIVAEFGTFPVDLTKTRLQVQGQSIDARFKEIKYRG
309326444
Protein Sequence	MFHALFRTCKEEGVLALYSGIAPALLRQASYGTIKIGIYQSLKRLFVERLEDETLLINMICGVVSGV
	ISSTIANPTDVLKIRMQAQGSLFQGSMIGSFIDIYQQEGTRGLWRGVVPTAQRAAIVVGVELPVYDI
	TKKHLILSGMMGHVDLYKGTVDGILKMWKHEGFFALYKGFWPNWLRLGPWNIIFFITYEQVKRLQIV
	DG
	SEQ ID NO: 149	761 bp
NOV35d,	CACCGGATCCCTGAATTGCAAACCCTTTGTATATGGCGGCCTTGCCTCTATCGTGGCTGAGTTTGGG
309326473 DNA
Sequence	ACTTTCCCTGTGGACCTTACCAAAACACGACTTCAGGTTCAAGGCCAAAGCATTGATGCCCGTTTCA
	AAGAGATAAAATATAGAGGGATGTTCCATGCGCTGTTTCGCATCTGTAAAGAGGAAGGTGTATTGGC
	TCTCTATTCAGGAATTGCTCCTGCGTTGCTAAGACAAGCATCATATGGCACCATTAAAATTGGGATT
	TACCAAAGCTTGAAGCGCTTATTCGTAGAACGTTTAGAAGATGAAACTCTTTTAATTAATATGATCT
	GTGGGGTAGTGTCAGGAGTGATATCTTCCACTATAGCCAATCCCACCGATGTTCTAAAGATTCGAAT
	GCAGGCTCAAGGAAGCTTGTTCCAAGGGAGCATGATTGGAAGCTTTATCGATATATACCAACAAGAA
	GGCACCAGGGGTCTGTGGAGGGGTGTGGTTCCAACTGCTCAGCGTGCTGCCATCGTTGTAGCAGTAG
	AGCTACCAGTCTATGATATTACTAAGAAGCATTTAATATTGTCAGGAATGATGGGACATGTGGATCT
	CTATAAGGGCACTGTTGATGGTATTTTAAAGATGTGGAAACATGAGGGCTTTTTTGCACTCTATAAA
	GGATTTTGGCCAAACTGGCTTCGGCTTGGACCCTGGAACATCATTTTTTTTATTACATACGAGCAGG
	TAAAGAGGCTTCAAATCGTCGACG
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO: 150	254 aa	MW at 28488.2 kD
NOV35d,	TGSLNWKPFVYGGLASIVAEFGTFPVDLTKTRLQVQGQSIDARFKEIKYRGMFHALFRICKEEGVLA
309326473
Protein Sequence	LYSGIAPALLRQASYGTIKIGIYQSLKRLFVERLEDETLLINMICGVVSGVISSTIANPTDVLKTRM
	QAQGSLFQGSMIGSEIDIYQQEGTRGLWRGVVPTAQRAAIVVGVELPVYDITKKHLILSGMMGHVDL
	YKGTVDGILKMWKHEGFFALYKGFWPNWLRLGPWNIIFFITYEQVKRLQIVDX
	SEQ ID NO: 151	1019 bp
NOV35e,	CTACCCAGAGGGTGAATGGGTATCTTTCCCGGAATAATCCTAATTTTTCTAAGGGTGAAGTTTGCAA
CG149964-02
DNA Sequence	CGGCGGCCGTGACTGTAAGCGGACACCAGAAAAGTACCACTGTAAGTCATGAGATGTCTGGTCTGAA
	TTGGAAACCCTTTGTATATGGCGGCCTTGCCTCTATCGTGGCTGAGTTTGGGACTTTCCCTGTGGAC
	CTTACCAAAACACGACTTCAGGTTCAAGGCCAAAGCATTGATGCCCGTTTCAAAGAGATAAAATATA
	GAGGGATGTTCCATGCGCTGTTTCGCATCTGTAAAGAGGAAGGTGTATTGGCTCTCTATTCAGGAAT
	TGCTCCTGCGTTGCTAAGACAAGCATCATATGGCACCATTAAAATTGGGATTTACCAAAGCTTGAAG
	CGCTTATTCGTAGAACGTTTAGAAGATGAAACTCTTTTAATTAATATGATCTGTGGGGTAGTGTCAG
	GAGTGATATCTTCCACTATAGCCAATCCCACCGATGTTCTAAAGATTCGAATGCAGGCTCAAGGAAG
	CTTGTTCCAAGGGAGCATGATTGGAAGCTTTATCGATATATACCAGCAAGAAGGCACCAGGGGTCTG
	TGGAGGGGTGTGGTTCCAACTGCTCAGCGTGCTGCCATCGTTGTAGGAGTAGAGCTACCAGTCTATG
	ATATTACTAAGAAGCATTTAATATTGTCAGGAATGATGGGCGATACAATTTTAACTCACTTCGTTTC
	CAGCTTTACATGTGGTTTGGCTGGGGCTCTGGCCTCCAACCCGGTTGATGTGGTTCGAACTCGCATG
	ATGAACCAGAGGGCAATCGTGGGACATGTGGATCTCTATAAGGGCACTGTTGATGGTATTTTAAAGA
	TGTGGAAACATCAGCGCTTTTTTGCACTCTATAAAGGATTTTGGCCAAACTGGCTTCGGCTTGGACC
	CTGGAACATCATTTTTTTTATTACATACGAGCAGGTAAAGAGGCTTCAAATCTAAGAACTGAATTAT
	ATGTGAGCCCAGCC
	ORF Start: ATG at 16		ORF Stop: TAA at 991
	SEQ ID NO: 152	325 aa	MW at 36175.2 kD
NOV35e,	MGIFPGIILIFLRVKFATAAVTVSGHQKSTTVSHEMSGLNWKPFVYGGLASIVAEFGTFPVDLTKTR
CG149964-02
Protein Sequence	LQVQGQSIDARFKEIKYRGMFHALFRICKEEGVLALYSGIAPALLRQASYGTIKIGIYQSLKRLFVE
	RLEDETLLINMICGVVSGVISSTIANPTDVLKIRMQAQGSLFQGSMTGSFIDIYQQEGTRGLWRGVV
	PTAQRAAIVVGVELPVYDITKKHLILSGMMGDTILTHFVSSFTCGLAGALASNPVDVVRTRMMNQRA
	IVGHVDLYKGTVDGILKMWKHEGFFALYKGFWPNWLRLGPWNIIFFITYEQVKRLQI

[0528] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 35B.

TABLE 35B
Comparison of NOV35a against NOV35b through NOV35e.
Protein	NOV35a Residues/	Identities/
Sequence	Match Residues	Similarities for the Matched Region
NOV35b	1 . . . 286	282/286 (98%)
	5 . . . 287	282/286 (98%)
NOV35c	26 . . . 286	261/261 (100%)
	7 . . . 267	261/261 (100%)
NOV35d	39 . . . 286	248/248 (100%)
	4 . . . 251	248/248 (100%)
NOV35e	1 . . . 286	286/325 (88%)
	1 . . . 325	286/325 (88%)

[0529] Further analysis of the NOV35a protein yielded the following properties shown in Table 35C.

TABLE 35C
Protein Sequence Properties NOV35a
PSort analysis:   0.4600 probability located in plasma membrane;
                  0.2648 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 20 and 21

[0530] 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
		NOV35a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAY94665	Human uncoupling protein	1 . . . 286	284/325 (87%)	e−158
	(UCP5) amino acid sequence -	1 . . . 325	285/325 (87%)
	Homo sapiens, 325 aa.
	[WO200032624-A2, 08-JUN-2000]
ABG33878	Human secreted protein	1 . . . 286	284/334 (85%)	e−155
	encoded by gene 16 - Homo	1 . . . 334	285/334 (85%)
	sapiens, 334 aa.
	[WO200226931-A2, 04-APR-2002]
AAE06056	Human gene 16 encoded	1 . . . 286	284/334 (85%)	e−155
	secreted protein HMIAP86,	1 . . . 334	285/334 (85%)
	SEQ ID NO:118 - Homo
	sapiens, 334 aa.
	[WO200151504-A1, 19-JUL-2001]
AAY87079	Human secreted protein	1 . . . 286	284/334 (85%)	e−155
	sequence SEQ ID NO:118 -	1 . . . 334	285/334 (85%)
	Homo sapiens, 335 aa.
	[WO200004140-A1, 27-JAN-2000]
AAY94666	Human uncoupling protein	1 . . . 286	281/325 (86%)	e−154
	isoform hUCP5S amino acid	1 . . . 322	282/325 (86%)
	sequence - Homo sapiens,
	322 aa. [WO200032624-A2,
	08-JUN-2000]

[0531] 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
		NOV35a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched
Number	Protein/Organism/Length	Residues	Portion	Expect Value
O95258	Brain mitochondrial carrier	1 . . . 286	284/325 (87%)	e−157
	protein-1 (BMCP-1)	1 . . . 325	285/325 (87%)
	(Mitochondrial uncoupling
	protein 5)(UCP 5)(Solute
	carrier family 25, member 14) -
	Homo sapiens (Human), 325
	aa.
Q9Z2B2	Brain mitochondrial carrier	1 . . . 286	276/325 (84%)	e−154
	protein-1 (BMCP-1)	1 . . . 325	283/325 (86%)
	(Mitochondrial uncoupling
	protein 5)(UCP 5)(Solute
	carrier family 25, member 14) -
	Mus musculus (Mouse), 325
	aa.
Q9EP88	Brain mitochondrial carrier	1 . . . 286	274/325 (84%)	e−153
	protein BMCP1 (Brain	1 . . . 325	282/325 (86%)
	mitochondrial carrier
	protein-1) - Rattus norvegicus
	(Rat), 325 aa.
Q9JMH0	Brain mitochondrial carrier	1 . . . 286	271/325 (83%)	e−149
	protein-1 - Rattus norvegicus	1 . . . 322	279/325 (85%)
	(Rat), 322 aa.
Q8R206	Similar to RIKEN cDNA	36 . . . 232	160/197 (81%)	1e−87
	4933433D23 gene - Mus	1 . . . 197	176/197 (89%)
	musculus (Mouse), 210 aa.

[0532] PFam analysis predicts that the NOV35a protein contains the domains shown in the Table 35F.

TABLE 35F
Domain Analysis of NOV35a
		Identities/
Pfam		Similarities	Expect
Domain	NOV35a Match Region	for the Matched Region	Value
mito_carr	39 . . . 138	39/126 (31%)	5.7e−24
		78/126 (62%)
mito_carr	140 . . . 231	29/125 (23%)	4.4e−27
		76/125 (61%)
mito_carr	233 . . . 286	24/125 (19%)	0.0072
		46/125 (37%)

Example 36

[0533] 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: 153	1144 bp
NOV36a,	CGCGGGGCGCGCGGCGCGGGGCGGCCTGGCCGGCGGCGGCGGCGGCATGAAGGTCACGTCGCTCGAC
CG150306-01
DNA Sequence	GGGCGCCAGCTGCGCAAGATGCTCCGCAAGGAGGCGGCGGCGCGCTGCGTGGTGCTCGACTGCCGGC
	CCTATCTGGCCTTCGCTGCCTCGAACGTGCGCGGCTCGCTCAACGTCAACCTCAACTCGGTGGTGCT
	GGACCAGGGCAGCCGCCACTGGCAGAACCTGCGAGAGGAGAGCCCCGCGCGTGTCGTCCTCACCTCG
	CTACTCGCTTGCCTACCCGCCGGCCCGCGGGTCTACTTCCTCAAAGGGGGATATGAGACTTTCTACT
	CGGAATATCCTGAGTGTTGCGTGGATGTAAAACCCATTTCACAAGAGAAGATTGAGAGTGAGAGAGC
	CCTCATCAGCCAGTGTGGAAAACCAGTGGTAAATGTCAGCTACAGGCCAGCTTATCACCAGGGTGGC
	CCAGTTGAAATCCTTCCCTTCCTCTACCTTCGAAGTGCCTACCATGCATCCAAGTGCGAGTTCCTCG
	CCAACTTGCACATCACAGCCCTCCTGAATGTCTCCCGACGGACCTCCGACGCCTGCATGACCCACCT
	ACACTACAAATGGATCCCTGTGGAAGACAGCCACACGGCTGACATTAGCTCCCACTTTCAAGAAGCA
	ATAGACTTCATTGACTGTGTCAGGGAAAAGGGAGGCAAGGTCCTGGTCCACTGTGAGGCTGGGATCT
	CCCGTTCACCCACCATCTGCATGGCTTACCTTATGAAGACCAAGCAGTTCCGCCTGAAGGAGGCCTT
	CGATTACATCAAGCAGAGGAGGAGCATGGTCTCGCCCAACTTTGGCTTCATGGGCCAGCTCCTGCAG
	TACGAATCTGAGATCCTGCCCTCCACGCCCAACCCCCAGCCTCCCTCCTGCCAAGGGGAGGCAGCAG
	GCTCTTCACTGATAGGCCATTTGCAGACACTGAGCCCTGACATGCAGGGTGCCTACTGCACATTCCC
	TGCCTCGGTGCTGGCACCGGTGCCTACCCACTCAACAGTCTCAGAGCTCAGCAGAAGCCCTGTGGCA
	ACGGCCACATCCTGCTAAAACTGGGATGGAGGAATCGGCCCAGCCCCAAGAGCAACTGTGATTTTTG
	TTTTT
	ORF Start: ATG at 47		ORF Stop: TAA at 1088
	SEQ ID NO: 154	347 aa	MW at 38362.6 kD
NOV36a,	MKVTSLDGRQLRKMLRKEAAARCVVLDCRPYLAFAASNVRGSLNVNLNSVVLDQGSRHWQKLREESA
CG150306-01
Protein Sequence	ARVVLTSLLACLPAGPRVYFLKGGYETFYSEYPECCVDVKPISQEKIESERALISQCGKPVVNVSYR
	PAYDQGGPVEILPFLYLGSAYHASKCEFLANLHITALLNVSRRTSEACMTHLHYKWIPVEDSHTADI
	SSHFQEAIDFIDCVREKGGKVLVHCEAGISRSPTICMAYLMKTKQFRLKEAFDYIKQRRSMVSPNFG
	FMGQLLQYESEILPSTPNPQPPSCQGEAAGSSLIGHLQTLSPDMQGAYCTFPASVLAPVPTHSTVSE
	LSRSPVATATSC

[0534] Further analysis of the NOV36a protein yielded the following properties shown in Table 36B.

TABLE 36B
Protein Sequence Properties NOV36a
PSort analysis:   0.4811 probability located in mitochondrial matrix
                  space; 0.4500 probability located in cytoplasm;
                  0.1892 probability located in mitochondrial inner
                  membrane; 0.1892 probability located in mitochondrial
                  intermembrane space
SignalP analysis: No Known Signal Sequence Predicted

[0535] 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 36C.

TABLE 36C
Geneseq Results for NOV36a
		NOV36a	Identities/
		Residues/	Similarities
Geneseq	Protein/Organism/Length	Match	for the	Expect
Identifier	[Patent #, Date]	Residues	Matched Region	Value
ABB07842	Amino acid sequence of	1 . . . 347	347/384 (90%)	0.0
	protein identified by	1 . . . 384	347/384 (90%)
	Swissprot Accn No. Q16690 -
	Homo sapiens, 384 aa.
	[WO200220732-A2,
	14 MAR. 2002]
AAB66440	Human MAP-kinase	116 . . . 286	171/171 (100%)	1e−97
	phosphatase MKP-5 - Homo	1 . . . 171	171/171 (100%)
	sapiens, 171 aa.
	[WO200102582-A1,
	11 JAN. 2001]
AAE06784	Human dual-specificity	116 . . . 286	171/171 (100%)	1e−97
	phosphatase (DSP) protein,	1 . . . 171	171/171 (100%)
	MKP-5 - Homo sapiens, 171
	aa. [WO200157221-A2,
	09 AUG. 2001]
AAR63602	MAP-kinase-phosphatase	1 . . . 347	168/388 (43%)	5e−72
	CL100 - Homo sapiens, 367	3 . . . 367	220/388 (56%)
	aa. [WO9423039-A,
	13 OCT. 1994]
AAU84270	Human endometrial cancer	1 . . . 347	167/388 (43%)	1e−70
	related protein, DUSP1 -	3 . . . 367	219/388 (56%)
	Homo sapiens, 367 aa.
	[WO200209573-A2,
	07 FEB. 2002]

[0536] 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 36D.

TABLE 36D
Public BLASTP Results for NOV36a
			Identities/
Protein			Similarities for
Accession		NOV36a Residues/	the Matched	Expect
Number	Protein/Organism/Length	Match Residues	Portion	Value
Q16690	Dual specificity protein	1 . . . 347	347/384 (90%)	0.0
	phosphatase 5 (EC 3.1.3.48)	1 . . . 384	347/384 (90%)
	(EC 3.1.3.16) (Dual
	specificity protein
	phosphatase hVH3) - Homo
	sapiens (Human), 384 aa.
O54838	Dual specificity protein	1 . . . 347	320/384 (83%)	0.0
	phosphatase 5 (EC 3.1.3.48)	1 . . . 384	336/384 (87%)
	(EC 3.1.3.16) (MAP-kinase
	phosphatase CPG21) - Rattus
	norvegicus (Rat), 384 aa.
Q90W58	MAP kinase phosphatase	13 . . . 347	164/378 (43%)	9e−72
	XCL100 (beta) protein -	15 . . . 369	217/378 (57%)
	Xenopus laevis (African
	clawed frog), 369 aa.
P28562	Dual specificity protein	1 . . . 347	167/388 (43%)	3e−70
	phosphatase 1 (EC 3.1.3.48)	3 . . . 367	219/388 (56%)
	(EC 3.1.3.16) (MAP kinase
	phosphatase-1) (MKP-1)
	(Protein-tyrosine phosphatase
	CL100) (Dual specificity
	protein phosphatase hVH1) -
	Homo sapiens (Human), 367
	aa.
O42253	Dual specificity protein	15 . . . 344	166/366 (45%)	1e−68
	phosphatase 1 (EC 3.1.3.48)	4 . . . 353	213/366 (57%)
	(EC 3.1.3.16) (MAP kinase
	phosphatase-1) (MPK-1)
	(MAP kinase phosphatase-1) -
	Gallus gallus (Chicken), 353
	aa (fragment).

[0537] PFam analysis predicts that the NOV36a protein contains the domains shown in the Table 36E.

TABLE 36E
Domain Analysis of NOV36a
		Identities/
	NOV36a	Similarities
	Match	for the Matched	Expect
Pfam Domain	Region	Region	Value
Rhodanese	7 . . . 98	23/134 (17%)	0.0052
		66/134 (49%)
DSPc	141 . . . 279	76/172 (44%)	1.8e−70
		132/172 (77%)
Y_phosphatase	44 . . . 279	39/336 (12%)	0.54
		144/336 (43%)

Example 37

[0538] 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	2277 bp
NOV37a,	CGCGTTCTCGGCTCCCGCCGGGGTCCCCCGCGGCTGTCGCCGCCGCCTACGCCGCTCCCTCCGCCTT
CG150510-01
DNA Sequence	CCTGCCCCGCGTCGGGCCGGGCGCCACCTCCCCCCTGCCTCCCTCTCCGCTCTGGTCATTTAGGAAA
	TCGTAAATCATGTGAAGATGGGACTCTTGGTATTTGTGCGCAATCTGCTGCTAGCCCTCTGCCTCTT3
	TCTGGTACTCGGATTTTTGTATTATTCTGCGTGGAAGCTACACTTACTCCAGTGGGAGGACGACTCC
	AGTAAGTATAGTCACTCTAGCTCACCCCAGGAGAAGCCTGTTGCAGATTCACTGGTTCTTTCCTTTG
	ACTCCGCTGGACAAACACTAGGCTCAGAGTATGATCGGTTGGGCTTCCTCCTGAATCTGGACTCTAA
	ACTGCCTGCTGAATTAGCCACCAAGTACGCAAACTTTTCAGAGGGAGCTTGCAAGCCTGGCTATGCT
	TCAGCCTTGATGACGGCCATCTTCCCCCGGTTCTCCAAGCCAGCACCCATGTTCCTGGATGACTCCT
	TTCGCAAGTGGGCTAGAATCCGGGAGTTCGTGCCGCCTTTTGGGATCAAAGGTCAAGACAATCTGAT
	CAAAGCCATCTTGTCAGTCACCAAAGAGTACCGCCTGACCCCTGCCTTGGACAGCCTCCGCTGCCGC
	CGCTGCATCATCGTGGGCAATGGAGGCGTTCTTGCCAACAAGTCTCTGGGGTCACGAATTGACGACT
	ATGACATTGTGGTGAGACTGAATTCAGCACCAGTGAAAGGCTTTGAGAAGGACGTGGGCAGCAAAAC
	GACACTGCGCATCACCTACCCCCAGGGCGCCATGCAGCGGCCTGAGCAGTACGAGCGCGATTCTCTC
	TTTGTCCTCGCCGGCTTCAAGTGGCAGGACTTTAAGTGGTTGAAATACATCGTCTACAAGGAGAGAG
	TGAGTGCATCGGATGGCTTCTGCAAATCTGTGGCCACTCGAGTGCCCAAGGAGCCCCCTGAGATTCG
	AATCCTCAACCCATATTTCATCCAGGAGGCCGCCTTCACCCTCATTGGCCTGCCCTTCAACAATGGC
	CTCATGGGCCGGGGGAACATCCCTACCCTTGGCAGTGTGGCAGTCACCATGGCACTACACGGCTGTG
	ACGAGGTGGCAGTCGCAGGATTTGGCTATGACATGAGCACACCCAACGCACCCCTGCACTACTATGA
	GACCGTTCGCATGGCAGCCATCAAAGAGTCCTGGACGCACAATATCCAGCGAGAGAAAGAGTTTCTG
	CGGAAGCTGGTGAAAGCTCGCGTCATCACTGATCTAAGCAGTGGCATCTGAGTGGGCCCAGCACATG
	GCCATAGAGGCCCAGGCACCACCAGGAGCAGCAGCCAGCACCACCTACACACGAGTCTTCAGACCCA
	GAGAAGGACGGTGCCAAGGGCCCCAGGGGCAGCAAGGCCTTGGTGGAGCAGCCAGAGCTGTGCCTGC
	TCAGCAGCCAGTCTCAGAGACCAGCACTCAGCCTCATTCAGCATGGGTCCTTGATGCCAGAGGGCCA
	GCAGGCTCCTGGCTGTGCCCAGCACGCCCAGCATGCAGGTGGTGGGACACTGGGCAGCAAGGCTGCT
	GCCGGAATCACTTCTCCAATCAGTGTTTGGTGTATTATCATTTTGTGAATTTGGGTAGGGGGGAGGG
	TAGGGATAATTTATTTTTAAATAAGGTTGGAGATGTCAAGTTGGGTTCACTTGCCATGCAGGAAGAG
	GCCCACTAGAGGGCCCATCAGGCAGTGTTACCTGTTAGCTCCCTGTGGGGCAGGAGTGCCAGGACCA
	GCCTGTACCTTGCTGTGGGGCTACAGGATGGTGGGCAGGATCTCAAGCCAGCCCCCTCCAGCTCATG
	ACACTGTTTGGCCTTTCTTGGGGAGAAGGCGGGGTATTCCCACTCACCAGCCCTAGCTGTCCCATGG
	GGAAACCCTGGAGCCATCCCTTCGGAGCCAACAAGACCGCCCCAGCGCTATAGCAGAAAGAACTTTA
	AAGCTCAGCAGGGTGACGCCCAGCTCCGCCTGCTGGGAAGAGCTCCCCTCCACAGCTGCAGCTGATC
	CATAGGACTACCGCAGGCCCGGACTCACCAACTTGCCACATGTTCTAGGTTTCAGCAACAAGACTGC
	CAGGTGGTTGGGTTCTGCCTTTAGCCTGGACCAAAGGGAAGTGAGGCCCAAGGAGCTTACCCAAGCT
	GTGGCAGCCGTCCCAGGCCACCCCCATGGAAGCAATAAAGCTCTTCCCTGTAAAAAAAAAAAAAAA
	ORF Start: ATG at 152		ORF Stop: TGA at 1322
	SEQ ID NO: 156	390 aa	MW at 43785.1 kD
NOV37a,	MGLLVFVRNLLLALCLFLVLGFLYYSAWKLHLLQWEEDSSKYSHSSSPQEKPVADSVVLSFDSAGQT
CG150510-01
Protein Sequence	LGSEYDRLGFLLNLDSKLPAELATKYANFSEGACKPGYASALMTAIFPRFSKPAPMFLDDSFRKWAR
	IREFVPPFGIKGQDNLIKAILSVTKEYRLTPALDSLRCRRCIIVGNGGVLANKSLGSRIDDYDIVVR
	LNSAPVKGFEKDVGSKTTLRITYPEGAMQRPEQYERDSLFVLAGFKWQDEKWLKYIVYKERVSASDG
	FWKSVATRVPKEPPEIRILNPYFIQEAAFTLIGLPFNNGLMGRGNIPTLGSVAVTMALHGCDEVAVA
	GFGYDMSTPNAPLHYYETVRMAAIKESWTHNIQREKEFLRKLVKARVITDLSSGI

[0539] Further analysis of the NOV37a protein yielded the following properties shown in Table 37B.

TABLE 37B
Protein Sequence Properties NOV37a
PSort analysis:   0.8200 probability located in outside; 0.2360
                  probability located in microbody (peroxisome);
                  0.1900 probability located in lysosome (lumen);
                  0.1000 probability located in endoplasmic
                  reticulum (membrane)
SignalP analysis: Cleavage site between residues 22 and 23

[0540] A search of the NOV37a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 37C.

TABLE 37C
Geneseq Results for NOV37a
			Identities/
			Similarities for
Geneseq	Protein/Organism/Length	NOV37a Residues/	the Matched	Expect
Identifier	[Patent #, Date]	Match Residues	Region	Value
AAY39960	Human alpha2-3 sialate	1 . . . 390	374/390 (95%)	0.0
	transferase protein sequence -	1 . . . 375	375/390 (95%)
	Homo sapiens, 375 aa.
	[JP11253163-A,
	21 SEP. 1999]
AAR65242	Human ST3N	1 . . . 390	374/390 (95%)	0.0
	sialyltransferase - Homo	1 . . . 375	375/390 (95%)
	sapiens, 375 aa.
	[W09504816-A,
	16 FEB. 1995]
AAR63217	Human	1 . . . 390	374/390 (95%)	0.0
	alpha-2, 3-sialyltransferase	1 . . . 375	375/390 (95%)
	(WM16) - Homo sapiens
	(melanoma WM266-4 cells),
	375 aa. [WO9423021-A,
	13 OCT. 1994]
AAR62808	Alpha 2, 3-sialyl transferase -	1 . . . 390	374/390 (95%)	0.0
	Homo sapiens, 375 aa.	1 . . . 375	375/390 (95%)
	[JP06277052-A,
	04 OCT. 1994]
AAR41671	Rat sialyltransferase - Rattus	1 . . . 390	361/390 (92%)	0.0
	rattus, 374 aa.	1 . . . 374	370/390 (94%)
	[WO9318157-A,
	16 SEP. 1993]

[0541] 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 37D.

TABLE 37D
Public BLASTP Results for NOV37a
			Identities/
Protein			Similarities for
Accession		NOV37a Residues/	the Matched	Expect
Number	Protein/Organism/Length	Match Residues	Portion	Value
Q11203	CMP-N-acetylneuraminate-beta-1,4-	1 . . . 390	374/390 (95%)	0.0
	galactoside alpha-2,3-sialyltransferase	1 . . . 375	375/390 (95%)
	(EC 2.4.99.6) (N-acetyllactosaminide
	alpha-2,3-sialyltransferase) (Gal
	beta-1,3(4) GlcNAc alpha-2,3
	sialyltransferase) (ST3N)
	(Sialyltransferase 6) - Homo sapiens
	(Human), 375 aa.
Q922X5	Sialyltransferase (N-acetyllacosaminide	1 . . . 390	361/390 (92%)	0.0
	alpha 2,3-sialyltransferase) - Mus	1 . . . 374	371/390 (94%)
	musculus (Mouse), 374 aa.
Q9DBB6	Sialyltransferase (N-acetyllacosaminide	1 . . . 390	360/390 (92%)	0.0
	alpha 2,3- sialyltransferase) - Mus	1 . . . 374	371/390 (94%)
	musculus (Mouse), 374 aa.
Q02734	CMP-N-acetylneuraminate-beta-1,4-	1 . . . 390	361/390 (92%)	0.0
	galactoside alpha-2,3- sialyltransferase	1 . . . 374	370/390 (94%)
	(EC 2.4.99.6) (N-acetyllactosaminide
	alpha-2,3- sialyltransferase) (Gal
	beta-1,3(4) GlcNAc alpha-2,3
	sialyltransferase) (ST3N)
	(Sialyltransferase 6) - Rattus norvegicus
	(Rat), 374 aa.
P97325	CMP-N-acetylneuraminate-beta-1,4-	1 . . . 390	359/390 (92%)	0.0
	galactoside alpha-2,3- sialyltransferase	1 . . . 374	370/390 (94%)
	(EC 2.4.99.6) (N-acetyllactosaminide
	alpha-2,3- sialyltransferase) (Gal
	beta-1,3(4) GlcNAc alpha-2,3
	sialyltransferase) (ST3N)
	(Sialyltransferase 6) - Mus musculus
	(Mouse), 374 aa.

[0542] PFam analysis predicts that the NOV37a protein contains the domains shown in the Table 37E.

TABLE 37E
Domain Analysis of NOV37a
		Identities/
	NOV37a	Similarities
	Match	for the	Expect
Pfam Domain	Region	Matched Region	Value
Glyco_transf_29	101 . . . 389	108/324 (33%)	3.2e−116
		270/324 (83%)

Example 38

[0543] 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: 157	1976 bp
NOV38a,	CCCTTATGAAGACGGGACATTTTGAAATAGTCACCATGCTGCTGGCAACCATGATTCTAGTGGACAT
CG150704-01
DNA Sequence	TTTCCAGGTGAAGGCTGAAGTGTTAGACATGGCACATAATGCATTTGATGATGAATACCTGAAATGT
	ACGGACAGGATGGAAATTAAATACGTTCCCCAACTGCTAAAGGAGGAAAAAGCAAGCCACCAGCAAT
	TAGATACTGTGTGGGAAAATGCAAAAGCCAAATGCGCAGCCCCAAAGACTCAAATCTTTCTCCCTAT
	GAATTTTAAGGATAACCATGGAATAGCCCTGATGGCATATATTTCCGAACCTCAAGAGCAAACTCCC
	TTTTACCATCTGTTCAGTGAAGCTGTCAAGATGGCTGGCCAATCTCGAGAAGATTATATCTATGGCT
	TCCAGTTCAAAGCTTTCCACTTTTACCTCACAAGAGCCCTGCAGTTGCTGAGAAAACCTTGTGAGGC
	CAGTTCCAAAACTGTGGTATATAGAACAAGCCACGGCACTTCATTTACATTTGGAGGGCTAAACCAA
	GCCAGGTTTGGCCATTTTACCTTGGCATATTCAGCCAAACCTCAGGCTGCTAATGACCAGCTCACTG
	TGTTATCCATCTACACATGCCTTGGAGTTGACATTCAAAATTTTCTTCATAAAGAAAGTGAAAGAAT
	TACTTTAATACCTCTGAATGAGGTTTTTCAAGTGTCACAGGAGGGGGCTGGCAATAACCTTATCCTT
	CAAAGCATAAACAAGACCTGCAGCCATTATGAGTGTGCATTTCTACGTGGACTAAAAACCGAAAACT
	GTATTGAGAACCTAGAATATTTTCAACCCATCTATGTCTACAACCCTGGTGAGAAAAACCAGAAGCT
	TCAAGACCATAGTGAGAAAAACTGGAAGCTTGAAGACCATGGTGAGAAAAACCACAAGCTTGAAGAC
	CATGCTCCAGGTCCAGTTCCTGTTCCAGGTCCCAAAAGCCATCCTTCTGCATCCTCGGGCAAACTGC
	TGCTTCCACAGTTTGGGATGGTCATCATTTTAATCAGTGTTTCTGCTATAAATCTCTTTGTTGCTCT
	GTAG
	ORF Start: ATG at 6		ORF Stop: TAG at 1074
	SEQ NO: 158	356 aa	MW at 40311.7 kD
NOV38a,	MKTGHFEIVTMLLATMILVDIFQVKAEVLDMADNAFDDEYLKCTDRMEIKYVPQLLKEEKASHQQLD
CG150704-01
Protein Sequence	TVWENAKAKWAARKTQIFLPMNFKDNHGIALMAYISEAQEQTPFYHLFSEAVKMAGQSREDYIYGFQ
	FKAFHFYLTRALQLLRKPCEASSKTVVYRTSQGTSFTFGGLNQARFGHFTLAYSAKPQAANDQLTVL
	SIYTCLGVDIENFLDKESERITLIPLNEVFQVSQEGAGNNLILQSINKTCSHYECAPLGGLKTENCI
	ENLEYFQPIYVYNPGEKNQKLEDHSEKNWKLEDHGEKNQKLEDHAPGPVPVPGPKSHPSASSGKLLL
	PQFGMVIILISVSATMLFVAL

[0544] Further analysis of the NOV38a protein yielded the following properties shown in Table 38B.

TABLE 38B
Protein Sequence Properties NOV38a
PSort analysis:   0.6850 probability located in endoplasmic reticulum
                  (membrane); 0.6400 probability located in plasma
                  membrane; 0.4600 probability located in Golgi body;
                  0.1000 probability located in endoplasmic
                  reticulum (lumen)
SignalP analysis: Cleavage site between residues 27 and 28

[0545] 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
AAR41876	Human HT6 - Homo sapiens,	29 . . . 256	82/238 (34%)	1e−21
	230 aa. [DE4209216-A,	7 . . . 227	120/238 (49%)
	23 SEP. 1993]
AAW76806	Human	20 . . . 266	83/266 (31%)	6e−21
	ADP-ribosyltransferase	31 . . . 287	123/266 (46%)
	protein - Homo sapiens, 327
	aa. [US5834310-A,
	10 NOV. 1998]
AAW76804	Rabbit skeletal muscle	8 . . . 259	88/282 (31%)	1e−20
	ADP-ribosyltransferase	6 . . . 280	130/282 (45%)
	protein - Oryctolagus
	cuniculus, 327 aa.
	[US5834310-A,
	10 NOV. 1998]
AAR37572	Rabbit skeletal muscle	8 . . . 259	88/282 (31%)	1e−20
	ADP-ribosyltransferase -	6 . . . 280	130/282 (45%)
	Oryctolagus cuniculus, 327
	aa. [USN7985698-N,
	01 MAY 1993]
ABB97573	Novel human protein SEQ ID	29 . . . 163	59/137 (43%)	1e−20
	NO: 841 - Homo sapiens, 229	29 . . . 161	76/137 (55%)
	aa. [WO200222660-A2,
	21 MAR. 2002]

[0546] 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
S62906	mono-ADP-ribosyltransferase -	1 . . . 356	356/367 (97%)	0.0
	human, 367 aa.	1 . . . 367	356/367 (97%)
Q8WVJ7	Hypothetical 42.7 kDa protein -	1 . . . 356	355/378 (93%)	0.0
	Homo sapiens (Human), 378	1 . . . 378	355/378 (93%)
	aa.
Q13508	Ecto-ADP-ribosyltransferase 3	1 . . . 356	355/389 (91%)	0.0
	precursor (EC 2.4.2.31)	1 . . . 389	355/389 (91%)
	(NAD(P)(+)-- arginine
	ADP-ribosyltransferase 3)
	(Mono(ADP-ribosyl)transferase
	3) - Homo sapiens (Human),
	389 aa.
Q96HL1	Unknown (protein for	1 . . . 356	354/389 (91%)	0.0
	MGC: 14489) - Homo sapiens	1 . . . 389	354/389 (91%)
	(Human), 389 aa.
Q9GKV6	Hypothetical 38.2 kDa protein -	31 . . . 356	300/338 (88%)	e−174
	Macaca fascicularis (Crab	1 . . . 338	312/338 (91%)
	eating macaque) (Cynomolgus
	monkey), 338 aa.

[0547] PFam analysis predicts that the NOV38a protein contains the domains shown in the Table 38E.

TABLE 38E
Domain Analysis of NOV38a
			Identities/
		NOV38a	Similarities
	Pfam	Match	for the	Expect
	Domain	Region	Matched Region	Value
	ART	1 . . . 312	164/340 (48%)	1.5e−200
			312/340 (92%)

Example 39

[0548] 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: 159	8350 bp
NOV39a,	CAGGGAAAAGGGAACCTATGGAATGGTCATGGTGACTTTTGAGGTAGAGGGTGGCCCAAATCCCCCT
CG150799-01
DNA Sequence	GATGAAGATTTGAGTCCAGTTAAAGGAAATATCACCTTTCCCCCTGGCAGAGCAACAGAAATTTATA
	ACTTGACAGTACTCGATGACGAGGTACCAGAAAATGATGAAATATTTTTAATTCAACTGAAAAGTGT
	AGAAGGAGGAGCTGAGATTAACACCTCTAGGAATTCCATTGAGATCATCATTAAGAAAAATGATAGT
	CCCGTGAGATTCCTTCAGAGTATTTATTTGGTTCCTGAGGAAGACCACATACTCATAATTCCAGTAG
	TTCGTGGAAAGGACAACAATCGAAATCTCATTGGATCTGATGAATATGAGGTTTCAATCAGTTATGC
	TGTCACAACTGGGAATTCCACAGCACATGCCCAGCAAAATCTGGACTTCATTGATCTTCAGCCAAAC
	ACAACTGTTGTTTTTCCACCTTTTATTCATGAATCTCACTTGAAATTTCAAATAGTTGATGACACCA
	CACCGGAGATTGCTGAATCGTTTCACATTATGTTACTAAAAGATACCTTACAGGGAGATGCTGTGCT
	AATAAGCCCTTCTGTTGTACAAGTCACCATTAAGCCAAATGATAAACCTTATGGAGTCCTTTCATTC
	AACAGTGTTTTGTTTGAAAGGACAGTTATAATTGATCAAGATAGAATATCAAGATATGAAGAAATCA
	CAGTCGTTAGAAATGGAGGAACCCATGGGAATGTCTCTGCGAATTGGGTGTTGACACGGAACAGCAC
	TGATCCCTCACCAGTAACAGCACATATCAGACCGAGCTCTGGAGTTCTCCATTTTGCACAACGGCAG
	ATGTTGGCAACAATTCCTCTTACTGTGGTTGATGATGATCTTCCAGAAGAGGCAGAAGCTTATCTAC
	TTCAAATTCTGCCTCATACAATACGAGGACCTGCAGAAGTGAGCGAGCCAGCGGAGGATAGTGATGA
	TGTCTATGGCCTAATAACATTTTTTCCTATGGAAAACCAGAAGATTCAAAGCAGCCCAGGTGAACGA
	TACTTATCCTTGAGTTTTACAAGACTAGGAGGGACTAAAGGAGATGTGAGGTTGCTTTATTCTGTAC
	TTTACATTCCTGCTGGAGCTGTGGACCCCTTGCAAGCAAAAGAAGGCATCTTAAATATATCAAGGAG
	AAATGACCTCATTTTTCCAGAGCAAAAAACTCAAGTCACTACAAAATTACCAATAAGAAATGATGCA
	TTCTTTCAAAATGGAGCTCACTTTCTAGTACAGTTGCAAACTGTGGAGTTGTTAAACATAATTCCTC
	TAATCCCACCCATAAGCCCTAGATTTGGGGAAATCTGCAATATTTCTTTACTGGTTACTCCAGCCAT
	TGCAAATGGAGAAATTGGCTTTCTCAGCAATCTTCCAATTATTTTGCATGAACCAGAAGATTTTGCT
	GCTGAAGTGGTATACATTCCCTTACATCGGGATGGAACTGATGGCCAGGCTACTGTCTACTGGAGTT
	TGAAGCCCTCTGGCTTTAATTCAAAAGCAGTGACCCCCGATGATATAGGCCCCTTTAATGGCTCTGT
	TTTGTTTTTATCTGGGCAAAGTGACACAACAATCAACATTACTATCAAAGGTGATGACATACCGGAA
	ATGAATGAAACTGTAACACTTTCTCTAGACAGGGTTAACGTGGAAAACCAAGTGCTGAAATCTCGAT
	ATACTAGCCGTGACCTAATTATTTTGGAAAATGATGACCCTCGGGGAGTTTTTGAATTTTCTCCTGC
	TTCCAGAGGACCCTATGTTATAAAAGAAGGAGAATCTGTAGAGCTCCACATCATCCGATCAAGGGGG
	TCCCTTGTTAAGCAGTTTCTACACTACCGAGTAGAGCCAAGAGATAGCAATGAATTCTATGGAAACA
	CGGGAGTACTAGAATTTAAACCTGGAGAAAGGGAGATAGTGATCACCTTGCTAGCAAGATTCGATGG
	GATACCAGAGTTGGATGAACACTACTGGGTCGTCCTCAGCAGCCACGGAGAACGGGAAAGCAAGTTG
	CGAAGTGCCACCATTGTCAATATAACGATTCTGAAAAATGATGATCCTCATGGCATTATAGAATTTG
	TTTCTGATGGTCTAATTGTGATGATAAATGAAAGCAAAGGAGATGCTATCTATAGTGCTGTTTATGA
	TGTAGTAAGAAATCGAGGCAACTTTGGTGATGTTAGTGTATCATGGTTGGTTAGTCCAGACTTTACA
	CAAGATGTATTTCCTGTACAAGGGACTGTTGTCTTTGGAGATCACGAATTTTCAAAAAATATCACCA
	TTTACTCCCTTCCAGATGAGATTCCAGAAGAAATGGAAGAATTTACCGTTATCCTACTGAATGGCAC
	TGGAGGAGCTAAACTGGGAAATAGAACAACTGCAACTCTGAGGATTAGAAGAAATGATGACCCCATT
	TATTTTGCAGAACCTCGTGTAGTGAGGGTTCAGGAAGGTGAGACTGCCAACTTTACAGTTCTCAGAA
	ATGGATCTGTTGATGTGACTTGCATGGTCCAGTATGCTACCAAGGATGGGAAGGCTACTCCAAGAGA
	GAGAGATTTCATTCCTGTTGAAAAAGGAGAAACGCTCATTTTTGAGGTTGGAAGTAGACAGCAGAGC
	ATATCCATATTTGTTAATGAAGATGGTATCCCGGAAACAGATGAGCCCTTTTATATAATCCTCTTGA
	ATTCAACAGGTGATACAGTAGTATATCAATATGGAGTAGCTACAGTAATAATTGAAGCTAATGATGA
	CCCAAATGGCATTTTTTCTCTGGAGCCCATAGACAAAGCAGTGGAAGAAGGAAAGACTAATGCATTT
	TGGATTTTGAGGCACCGAGGATACTTTGGTAGTGTTTCTGTATCTTGGCAGCTCTTTCAGAATGATT
	CTGCTTTGCAGCCTGGGCAGGAGTTCTATGAAACTTCACGAACTGTTAACTTCATGGATGGAGAAGA
	AGCAAAACCAATCATTCTCCATGCTTTTCCAGATAAAATTCCTGAATTCAATGAATTTTATTTCCTA
	AAACTTGTAAACATTTCAGGTCCTCGGGGCCAGCTAGCAGAAACCAACCTCCAGGTGACACTAATGG
	TTCCATTCAATGATGATCCCTTTGGAGTTTTTATCTTGGATCCAGAGTGTTTAGAGAGAGAAGTGGC
	AGAAGATGTCCTGTCTGAAGATGATATGTCTTATATTACCAACTTCACCATTTTGACGCAGCAGGGT
	GTGTTTCGTGATGTACAACTGGGCTGGGAAATACTGTCCAGTGAGTTCCCTGCTGGTTTGCCACCAA
	TGATAGATTTTTTACTGGTTGGAATTTTCCCCACCACCGTGCATTTACAACAGCACATGCCGCGTCA
	CCACAGTGGAACGGATGCTTTGTACTTTACCGGACTAGAGGGTGCATTTGGGACTGTTAATCCAAAA
	TACCATCCCTCCAGGIATAATACAATTGCCAACTTTACATTCTCAGCTTGGGTAATGCCCAATGCCA
	ATACGAATGGATTCATTATAGCGAAGGATGACCGTAATGGAAGCATCTACTACGGGGTAAAAATACA
	AACAAACGAATCCCATGTGACACTTTCCCTTCATTATAAAACCTTGGGTTCCAATGCTACATACATT
	GCCAAGACAACAGTCATGAAATATTTAGAAGAAAGTGTTTGGCTTCATCTACTAATTATCCTGGAGG
	ATGGTATAATCGAATTCTACCTGGATGGAAATGCAATGCCCAGGGGAATCAAGAGTCTGAAAGGAGA
	AGCCATTACTGACGGTCCTGGGATACTGAGAATTGGAGCAGGGATAAATGGCAATGACAGATTTACA
	GGTCTGATGCAGGATGTGAGGTCCTATCAGCGGAAACTGACCCTTGAAGAAATTTATGAACTTCATG
	CCATGCCCGCAAAAAGTGATTTACACCCAATTTCTGGATATCTGGAGTTCAGACAGGGAGAAACTAA
	CAAATCATTCATTATTTCTGCAAGAGATGACAATGACGAGGAAGGAGAAGAATTATTCATTCTTAAA
	CTACTTTCTGTATATGGAGGAGCTCGTATTTCGGAAGAAAATACTACTGCAAGATTAACAATACAAA
	AAAGTGACAATGCAAATGGCTTGTTTCGTTTCACACGAGCTTGTATACCAGAGATTGCAGAGGAGGG
	ATCAACCATTTCTTGTGTGGTTGAGAGAACCAGAGGAGCTCTGGATTATGTGCATGTTTTTTACACC
	ATTTCACAGATTGAAACTGATGGCATTAATTACCTTGTTGATGACTTTGCTAATGCCAGTGGAACTA
	TTACATTCCTTCCTTGGCAGAGATCAGAGGTTCTGAATATATATGTTCTTGATGATGATATTCCTGA
	ACTTAATGAGTATTTCCGTGTGACATTGGTTTCTGCAATTCCTGGAGATGGGAAGCTAGGCTCAACT
	CCTACCAGTGGTGCAACCATAGATCCTGAAAAGGAAACGACTGATATCACCATCAAAGCTAGTGATC
	ATCCATATGGCTTGCTGCAGTTCTCCACAGGGCTCCCTCCTCAGCCTAACGACGCAATGACCCTGCC
	TGCAAGCAGCGTTCCACATATCACTGTGGAGGAGGAAGATGGAGAAATCACGTTATTGGTCATCCGT
	GCACACGGACTTCTGGCAAGGGTGACTGCGGAATTTAGAACAGTGTCCTTGACAGCATTCAGTCCTG
	AGGATTACCAGAATGTTGCTGGCACATTAGAATTTCAACCAGGAGAAAGATATAAATACATTTTCAT
	AAACATCACTGATAATTCTATTCCTGAACTGGAAAAATCTTTTAAAGTTGAGTTGTTAAACTTGGAA
	GGAGGAGTAGCTGAACTCTTTAGGGTTGATGGAAGTCGTAGTGCCAGTCTAGGAGTGGCTTCCCAAA
	TTCTACTGACAATTGCAGCCTCTGACCACGCTCATGGCGTATTTGAATTTAGCCCTGAGTCACTCTT
	TGTCAGTGGAACTGAACCAGAAGATGGGTATAGCACTGTTACATTAAATGTTATAAGACATCATGGA
	ACTCTGTCTCCAGTGACTTTGCATTGGAACATAGACTCTGATCCTGATGGTGATCTCGCCTTCACCT
	CTGGCAACATCACATTTGAGATTGGGCAGACGAGCGCCAATATCACTGTGGAGATATTGCCTGACGA
	AGACCCAGAACTCGATAAGGCATTCTCTGTGTCAGTCCTCAGTGTTTCCAGTGGTTCTTTGGGAGCT
	CATATTAATGCCACGTTAACAGTTTTGGCTAGTGATGATCCATATGGGATATTCATTTTTTCTGAGA
	AAAACAGACCTGTTAAAGTTGAGGAAGCAACCCAGAACATCACACTATCAATAATAAGGTTGAAAGG
	CCTCATGGGAAAAGTCCTTGTCTCATATGCAACACTAGATGATATGGAAAAACCACCTTATTTTCCA
	CCTAATTTAGCGAGACCAACTCAAGGAAGAGACTATATACCACCTTCTGGATTTGCTCTTTTTGGAG
	CTAATCAGAGTGAGGCAACAATAGCTATTTCAATTTTGGATGATGATGAGCCAGAAAGGTCCGAATC
	TGTCTTTATCGAACTACTCAACTCTACTTTAGTAGCGAAAGTACAGAGTCGTTCAATTCCAAATTCT
	CCACGTCTTGGGCCTAAGGTAGAAACTATTGCGCAACTAATTATCATTGCCAATGATGATGCATTTG
	GAACTCTTCAGCTCTCAGCACCAATTGTCCGAGTGGCAGAAAATCATGTTGGACCCATTATCAATGT
	GACTAGAACAGGAGGAGCATTTGCAGATGTCTCTGTGAAGTTTAAAGCTGTGCCAATAACTGCAATA
	GCTCGTGAAGATTATAGTATAGCTTCATCAGATGTGGTCTTGCTAGAAGGGGAAACCAGTAAAGCCG
	TGCCAATATATGTCATTAATGATATCTATCCTGAACTGGAAGAATCTTTTCTTGTCCAACTGATGAA
	TGAAACAACAGGAGGAGCCAGACTAGGGGCTTTAACAGAGGCAGTCATTATTATTGAGGCCTCTGAT
	GACCCCTATGGATTATTTGGTTTTCAGATTACTAAACTTATTGTAGAGGAACCTGAGTTTAACTCAG
	TGAAGGTAAACCTGCCAATAATTCGAAATTCTGGGACACTCGGCAATGTTACTGTTCAGTGGGTTGC
	CACCATTAATGGACAGCTTGCTACTGGCGACCTGCGAGTTGTCTCAGGTAATGTGACCTTTGCCCCT
	GGGGAAACCATTCAAACCTTGTTGTTAGAGGTCCTGGCTGACGACGTTCCGGAGATTGAAGAGGTTA
	TCCAAGTGCAACTAACTGATGCCTCTCGTGGAGGTACTATTGGGTTAGATCGAATTGCAAATATTAT
	TATTCCTGCCAATGATGATCCTTATGGTACAGTAGCCTTTGCTCAGATGGTTTATCGTGTTCAAGAG
	CCTCTGGAAAGAAGTTCCTGTGCTAATATAACTGTCAGGCGAAGCGGAGGGCACTTTGGTCGGCTGT
	TCTTGTTCTACAGTACTTCCGACATTCATGTAGTGGCTCTGGCAATGGAGGAAGGTCAAGATTTACT
	GTCCTACTATGAATCTCCAATTCAAGGGGTGCCTGACCCACTTTGGAGAACTTGGATGAATGTCTCT
	GCCGTCCCGGAGCCCCTGTATACCTGTGCCACTTTGTGCCTTAAGGAACAAGCTTGCTCAGCGTTTT
	CATTTTTCAGTGCTTCTGAGGGTCCCCAGTGTTTCTGGATGACATCATGGATCAGCCCACCTGTCAA
	CAATTCAGACTTCTGGACCTACAGGAAAAACATGACCAGGGTAGCATCTCTTTTTAGTGCTCAGGCT
	GTGGCTGGGAGTGACTATGAGCCTGTGACAAGGCAATGCGCCATAATGCAGGAAGGTGATGAATTCG
	CAAATCTCACAGTGTCTATTCTTCCTGATGATTTCCCAGAGATCGATGAGAGTTTTCTAATTTCTCT
	CCTTGAAGTTCACCTCATGAACATTTCAGCCAGTTTGAAAAATCAGCCAACCATAGGACAGCCAAAT
	ATTTCTACAGTTGTCATAGCACTAAATGGTGATGCCTTTGCAGTGTTTGTGATCTACAATATTACTC
	CCAATACTTCCGAAGATGGCTTATTTGTTGAAGTTCACGAGCAGCCCCAAACCTTGGTGCAGCTGAT
	CATACACAGGACAGGGGGCAGCTTAGGTCAAGTGCCAGTCGAATGGCGTCTTGTTGGTGCAACAGCT
	ACTGAAGGTTTAGATTTTATAGGTGCTGGAGAGATTCTGACCTTTGCTGAAGGTCAAACCAAAAAGA
	CAGTCATTTTAACCATCTTGGATGACTCTGAACCAGAGGATGACGAAAGTATCATAGTTAGTTTGCT
	GTACACTGAAGCTCGAAGTAGAATTTTGCCAAGCTCCGACACTGTTAGAGTGAACATTTTGCCCAAT
	GACAATGTGGCAGCAATTGTTAGCTTTCAGACAGCTTCCAGATCTGTCATAGGTCATGAACGAGAAA
	TTTTACAATTCCATGTGATAAGAACTTTCCCTGGTCGAGGAAATGTTACTGTTAACTGGAAAATTAT
	TGGCCAAAATCTAGAACTCAATTTTGCTAACTTTAGCGGACAACTTTTCTTTCCTGAGGGGTCGTTG
	AATACAACATTGTTTGTGCATTTGTTGGATGACAACATTCCTGAGGAGAAAGAAGTATACCAAGTCA
	TTCTGTATGATGTCAGGACACAAGGAGTTCCACCAGCCGGAATCGCCCTGCTTGATGCTCAAGGATA
	TGCACCTGTCCTCACAGTAGAACCCAGTGATGAACCACATGGAGTTTTAAATTTTGCTCTTTCATCA
	AGATTTGTCTTACTACAAGAGGCTAACATAACAATTCACCTTTTCATCAACAGAGAATTTGGATCTC
	TACGAGCTATCAATGTCACATATACCACGGTTCCTGGAATGCTGAGTCTGAAGAACCAAACACTACG
	AAACCTAGCAGAGCCAGAAGTTGATTTTGTCCCTATCATTCGCTTTCTGATTTTAGAAGAAGGGCAA
	ACAGCAGCAGCCATCAACATTACCATTCTTGAGGATGATGTACCAGAGCTAGAAGAATATTTCCTCG
	TGAATTTAACTTACGTTGGACTTACCATGCCTGCTTCAACTTCATTTCCTCCCACACTACGTATCAG
	GGGTTTCTTGTTTGTTTCTTTTTGCTCACTTCAAATGAAATGAAGAAACTTCATTTTTGAATCAGAA
	GTGATCATTGTCCTGTTTTGTTAATCTTACCTATGTGTTAAA
	ORF Start: ATG at 23		ORF Stop: TGA at 8282
	SEQ ID NO: 160	2753 aa	MW at 301743.8 kD
NOV39a,	NVMVTFEVECGPNPPDEDLSPVKGNITFPPGRATVIYNLTVLDDEVPENDEIFLIQLKSVEGGAEIN
CG150799-01
Protein Sequence	TSRNSIEIIIKKNDSPVRFLQSIYLVPEEDHILIIPVVRGKDNNGNLIGSDEYEVSISYAVTTGNST
	AHAQQNLDFIDLQFNTTVVFPPFTHESHLKFQIVDDTTFEIAESFHIMLLKDTLQGDAVLISPSVVQ
	VTIKPNDKPYGVLSFNSVLFERTVIIDEDRISRYEEITVVRNGGTHCNVSANWVLTRNSTDPSPVTA
	DIRPSSGVLHFAQGQMLATIPLTVVDDDLPEEAEAYLLQILPHTIRGGAEVSEPAEDSDDVYGLITF
	FPMENQKIESSPGERYLSLSFTRLGGTKGDVRLLYSVLYIPAGAVDPLQAKEGILNISRRNDLIFPE
	QKTQVTTKLPIRNDAFFQNGAHFLVQLETVELLNIIPLIPPISPRFGEICNISLLVTPAIANGEIGF
	LSNLPIILHEPEDFAAEVVYIPLHRDGTDGQATVYWSLKPSGFNSKAVTPDDIGPFNGSVLFLSGQS
	DTTINITIKGDDIPEMNETVTLSLDRVNVENQVLKSGYTSRDLIILENDDPGGVFEFSPASRGPYVI
	KEGESVELHIIRSRGSLVKQFLHYRVEPRDSNEFYGNTCVLEFKPGEREIVITLLARLDGIPELDEH
	YWVVLSSHGERESKLGSATIVNITILKNDDPHGIIEFVSDGLIVMINESKGDAIYSAVYDVVRNRGN
	FGDVSVSWVVSPDFTQDVFPVQGTVVFGDQEFSKNITIYSLPDEIPEEMEEFTVILLNGTGGAKVGN
	RTTATLRIRRNDDPIYFAEPRVVRVQEGETANFTVLRNGSVDVTCMVQYATKDGEATARERDFIPVE
	KGETLIFEVGSRQQSISIFVNEDGIFETDEPFYIILLNSTGDTVVYQYGVATVIIEANDDPNGIFSL
	EPIDKAVEEGKTNAFWILRHRGYFGSVSVSWQLFQNDSALQPGQEFYETSGTVNFMDGEEAKPIILH
	AFPDKIPEFNEFYFLKLVNISGPGGQLAETNLQVTVMVPFNDDPFGVFILDPECLEREVAEDVLSED
	DMSYITNFTILRQQGVFGDVQLGWEILSSEFPAGLPPMIDFLLVGIFPTTVHLQQHMRRHHSGTDAL
	YFTGLEGAFGTVNPKYHPSRNNTIANFTFSAWVMPNANTNGFIIAKDDCNGSIYYGVKIQTNESHVT
	LSLHYKTLGSNATYIAKTTVMXYLEESVWLHLLIILEDGIIEFYLDGNAMPRGIKSLKGEAITDGPG
	ILRIGAGINGNDRFTGLMQDVRSYERKLTLEEIYELHAMPAKSDLHPISGYLEFRQGETNKSFIISA
	RDDNDEEGEELFILKLVSVYGGARISEENTTARLTIQKSDNANGLFGFTGACIPEIAEEGSTISCVV
	ERTRGALDYVHVFYTISQIETDGINYLVDDFANASGTITFLPWQRSEVLNIYVLDDDIPELNEYFRV
	TLVSAIPGDGKLGSTPTSGASIDPEKETTDTTIKASDHPYGLLQFSTGLPPQPKDAMTLPASSVPHI
	TVEEEDGEIRLLVIRAQGLLGRVTAEFRTVSLTAFSPEDYQNVAGTLEFQPGERYKYIFINITDNSI
	PELEKSFKVELLNLEGGVAELFRVDGSGSASLGVASQILVTIAASDHAHGVFEFSPESLFVSGTEPE
	DGYSTVTLNVIRHHCTLSPVTLEWNIDSDPDGDLAFTSGNITFEIGQTSANITVEILPDEDPELDKA
	FSVSVLSVSSGSLGAHINATLTVLASDDFYGIFIFSEKNRPVKVEEATQNITLSIIRLKGLMGKVLV
	SYATLDDMEKPPYFPPNLARATQGRDYIPASGFALFGANQSEATIAISILDDDEPERSESVFIELLN
	STLVAKVQSRSIPNSPRLGPKVETIAQLIIIANDDAFGTLQLSAPIVRVAENHVCPIINVTRTGGAE
	ADVSVKFKAVPITAIAGEDYSIASSDVVLLEGETSKAVPIYVINDIYPELEESFLVQLMNETTGGAR
	LGALTEAVIIIEASDDFYGLFGFQITKLIVEEPEFNSVKVNLPIIRNSGTLGNVTVQWVATINGQLA
	TGDLRVVSGNVTFAPGETIQTLLLEVLADDVFEIEEVIQVQLTDASGGGTIGLDRIANIIIPANDDP
	YGTVAFAQMVYRVQEPLERSSCANITVRRSGGHFGRLLLFYSTSDIDVVALAMEEGQDLLSYYESPI
	QGVPDPLWRTWMNVSAVGEPLYTCATLCLKEQACSAFSFFSASEGPQCFWMTSWISPAVNNSDFWTY
	RKNMTRVASLFSGQAVAGSDYEPVTRQWAIMQEGDEFANLTVSILPDDFPEMDESFLISLLEVHLNN
	ISASLKNQPTIGQPNISTVVIALNGDAFGVFVIYNISPNTSEDGLFVEVQEQPQTLVELMIHRTGGS
	LGQVAVEWRVVGGTATEGLDFIGAGEILTFAEGETKKTVILTILDDSEPEDDESIIVSLVYTEGGSR
	ILPSSDTVRVNILANDNVAGIVSFQTASRSVIGHEGEILQFHVIRTFPGRGNVTVNWKIIGQNLELN
	FANFSGQLFFPEGSLNTTLFVHLLDDNIPEEKEVYQVILYDVRTQGVPPAGIALLDAQGYAAVLTVE
	ASDEPHGVLNFALSSRFVLLGEANITIGLFINREFGSLGAINVTYTTVPGMLSLKNQTVGNLAEPEV
	DFVPIIGFLILEEGETAAAINITILEDDVPELEEYFLVNLTYVGLTMAASTSFPPRLGMRGFLFVSF
	ORF Start: ATG at 23		ORF Stop: TAA at 11537
	SEQ ID NO: 162	3838 aa	MW at 421384.3 kD
NOV39b,	MVMVTFEVEGGPNPPDEDLSPVKGNITFPPGRATVIYNLTVLDDEVPENDEIFLIQLKSVEGGAEIN
CG150799-02
Protein Sequence	TSRNSIEIIIKKNDSPVRFLQSIYLVPEEDHILIIPVVRGKDNNGNLICSDEYEVSISYAVTTGNST
	AHAQQNLDFIDLQPNTTVVFPPFIHESHLKFQIVDDTTPEIAESFHIMLLKDTLQGDAVLISPSVVQ
	VTIKPNDKFYGVLSFNSVLFERTVIIDEDRISRYEEITVVRNGGTHGNVSANWVLTRNSTDPSPVTA
	DIRPSSGVLHFAQGQMLATIFLTVVDDDLPEEAEAYLLQILPHTIRGGAEVSEPAEDSDDVYGLTTF
	FPMENQKIESSFGERYLSLSFTRLGGTKGDVRLLYSVLYIPAGAVDPLQAKEGILNISRRNDLIFPE
	QKTQVTTKLPIRNDAFFQNCAHFLVQLETVELLNIIPLIPPISPRFGEICNISLLVTPAIANGEIGF
	LSNLPIILHEPEDFAAEVVYIPLHRDGTDGQATVYWSLKPSGFNSKAVTPDDIGPFNGSVLFLSGQS
	DTTINITIKGDDIPEMNETVTLSLDRVNVENQVLKSGYTSRDLIILENDDFGGVFEFSPASRGPYVI
	KEGESVELHIIRSRGSLVKQFLHYRVEPRDSNEFYGNTGVLEFKFGEREIVITLLARLDGIPELDEH
	YWVVLSSHGERESKLGSATIVNITILKNDDPHGIIEFVSDGLIVMINESKGDAIYSAVYDVVRNRGN
	FGDVSVSWVVSPDFTQDVFPVQGTVVFGDQEFSKNITIYSLPDEIPEEMEEFTVILLNGTGGAKVGN
	RTTATLRIRRNDDPIYFAEPRVVRVQEGETANFTVLRNGSVDVTCMVQYATKDGKATARERDFIPVE
	KGETLIFEVGSRQQSISIFVNEDGIPETDEPFYIILLNSTGDTVVYQYGVATVIIEANDDPNGIFSL
	EPIDKAVEEGKTNAFWILRHRGYFGSVSVSWQLFQNDSALQFGQEFYETSGTVNFHDGEEAKPIILE
	AFFDKIPEFNEFYFLKLVNISGPGCQLAETNLQVTVMVPFNDDPFGVFILDPECLEREVAEDVLSED
	DMSYITNFTILRQQGVFGDVQLGWETLSSEFPAGLPPMIDFLLVGIFPTTVHLQQHMRRHHSGTDAL
	YFTGLEGAFGTVNPKYHPSRNNTIANFTFSAWVMPNANTNGFIIAKDDGNGSIYYGVKIQTNESHVT
	LSLHYKTLGSNATYIAKTTVMKYLEESVWLHLLIILEDGIIEFYLDGNAMPRGIKSLKGEAITDGPG
	ILRIGAGINGNDRFTGLMQDVRSYERKLTLEEIYELHAMPAKSDLHPISGYLEFRQGETNKSFIISA
	RDDNDEEGEELFILKLVSVYGGARISEENTTARLTIQKSDNANGLFGFTGACIPEIAEEGSTISCVV
	ERTRGALDYVHVFYTISQIETDGINYLVDDFANASGTITFLPWQRSEVLNIYVLDDDIPELNEYFRV
	TLVSAIPGDGKLGSTPTSGASIDPEKETTDITIKASDHPYGLLQFSTGLPFQPKDAMTLPASSVPHI
	TVEEEDGEIRLLVIRAQGLLGRVTAEFRTVSLTAFSPEDYQNVAGTLEFQPGERYKYIFINITDNSI
	PELEKSFKVELLNLEGGVAELFRVDGSGSASLGVASQILVTIAASDHAHGVFEFSPESLFVSGTEPE
	DGYSTVTLNVIRHHGTLSPVTLHWNIDSDPDGDLAFTSGNITFEIGQTSANITVEILPDEDPELDKA
	FSVSVLSVSSGSLGAHINATLTVLASDDPYGIFIFSEKNRPVKVEEATQNITLSIIRLKGLMGKVLV
	SYATLDDMEKPFYFPPNLARATGGRDYIPASGFALFGANGSEATIAISILDDDEPERSESVFIELLN
	STLVAKVQSRSIPNSPRLGPKVETIAQLIIIANDDAFGTLQLSAPIVRVAENHVGPIINVTRTGGAF
	ADVSVKFKAVPTTAIAGEDYSIASSDVVLLEGETSKAVPIYVINDIYPELEESFLVQLMNETTGGAR
	LGALTEAVIIIEASDDPYGLFGFQITKLIVEEPEFNSVKVNLPIIRNSGTLGNVTVQWVATINGQLA
	TGDLRVVSGNVTFAPGETIQTLLLEVLADDVPEIEEVIQVQLTDASCGGTIGLDRIANIIIPANDDP
	YGTVAFAQMVYRVQEPLERSSCANITVRRSGGHFGRLLLFYSTSDIDVVALAMEEGQDLLSYYESPI
	QGVPDPLWRTWNNVSAVGEPLYTCATLCLKEQACSAFSFFSASEGPQCFWMTSWISPAVNNSDFWTY
	RKNMTRVASLFSGQAVAGSDYEPVTRQWAIMQEGDEFANLTVSILPDDFPEMDESFLISLLEVHLMM
	ISASLKNQPTIGQPNISTVVIALNGDAFGVFVIYSISPNTSEDGLFVEVQEQPQTLVELMIHRTGGS
	LGQVAVEWRVVGGTATEGLDFIGAGEILTFAEGETKKTVILTILDDSEPEDDESIIVSLVYTEGGSR
	ILPSSDTVRVNILANDNVAGIVSFQTASRSVIGHEGEILQFHVIRTFPCRGNVTVNWKIIGQNLELN
	FANFSGQLFFFEGSLNTTLFVHLLDDNIPEEKEVYQVILYDVRTQGVPPAGIALLDAQGYAAVLTVE
	ASDEPHGVLNFALSSRFVLLQEANITIQLFINREFGSLCAINVTYTTVPGMLSLKNQTVGNLAEPEV
	DFVPIIGFLILEEGETAAAINITILEDDVPELEEYFLVNLTYVGLTMAASTSFPPRLDSEGLTAQVI
	IDANDGARGVIEWQQSRFEVNETHGSLTLVAQRSREPLGHVSLFVYAQNLEAQVGLDYIFTPMILHF
	ADGERYXNVNIMILDDDIPEGDEKFQLILTNPSPGLELGKNTIALIIVLANDDGPGVLSFNNSEHFF
	LREPTALYVQESVAVLYIVREPAQGLFGTVTVQFIVTEVNSSNESKDLTPSKGYIVLEEGVRFKALQ
	ISAILDTEPEMDEYFVCTLFNPTGGARLGVHVQTLITVLQNQAPLCLFSISAVENRATSIDIEEANR
	TVYLNVSRTNGIDLAVSVQWETVSETAFGMRGMDVVFSVFQSFLDESASGWCFFTLENLIYGIMLRK
	SSVTVYRWQGIFIPVEDLNIENPKTCEAFNIGFSPYFVITHEERNEEKPSLNSVFTFTSGFKLFLVQ
	TIIILESSQVRYFTSDSQDYLIIASQRDDSELTQVFRWNCGSFVLHQKLPVRGVLTVALFNXGGSVF
	LAISQANARLNSLLFRWSGSGFINFQEVPVSGTTEVEALSSANDIYLIFAXNVFLGDQNSIDIFIWE
	MGQSSFRYFQSVDFAAVNRIESFTPASGIAHILLIGQDMSALYCWNSERNQFSFVLEVPSAYDVASV
	TVXSLNSSKNLIALVGAHSHIYELAYISSHSDFIPSSGELIFEPGEREATIAVNILDDTVPEKEESF
	KVQLKNPKGGAEIGINDSVTITILSNDDAYGIVAFAQNSLYKQVEEMEQDSLVTLNVERLKGTYGRI
	TIAWEADGSISDIFPTSGVILFTEGQVLSTITLTILADNIPELSEVVIVTLTRITTEGVEDSYKGAT
	IDQDRSKSVITTLPNDSPFGLVGWRAASVFIRVAEPKENTTTLQLQIARDKGLLGDIAIHLRAQPNF
	LLHVDNQATENEDYVLQETIIIMKENIKEAHAEVSILPDDLPELEEGFIVTITEVNLVNSDFSTGQP
	SVRRPGMEIAEIMIEENDDPRGIFMFHVTRGAGEVITAYEVPPPLNVLQVPVVRLAGSFCAVNVYWK
	ASPDSAGLEDFKPSHGILEFADKQVTAMIEITIIDDAEFELTETFNISLISVAGGGRLGDDVVVTVV
	IPQNDSFFGVFCFEEKTVS
	SEQ ID NO: 163	5102 bp
NOV39c,	CAGGGAAAACGGAACCTATCGAATGGTCATGGTGACTTTTGAGGTAGAGGGTGGCCCAAATCCCCCT
CG150799-03
DNA Sequence	GATGAAGATTTGAGTCCAGTTAAACGAAATATCACCTTTCCCCCTGGCAGAGCAACAGTAATTTATA
	ACTTGACAGTACTCGATGACGAGGTACCAGAAAATGATGAAATATTTTTAATTCAACTGAAAAGTGT
	AGAAGGAGGAGCTGAGATTAACACCTCTAGGAATTCCATTGACATCATCATTAACAAAAATGATAGT
	CCCGTGAGATTCCTTCAGAGTATTTATTTGGTTCCTCAGGAACACCACATACTCATAATTCCAGTAG
	TTCGTGGAAAGGACAACAATGGAAATCTGATTGGATCTGATGAATATGAGGTTTCAATCAGTTATGC
	TGTCACAACTGGGAATTCCACAGCACATGCCCAGCAAAATCTCCACTTCATTGATCTTCAGCCAAAC
	ACAACTGTTGTTTTTCCACCTTTTATTCATGAATCTCACTTGAAATTTCAAATAGTTGATGACACCA
	CACCGGAGATTGCTGAATCGTTTCACATTATGTTACTAAAACATACCTTACAGGGAGATGCTGTGCT
	AATAAGCCCTTCTGTTGTACAACTCACCATTAAGCCAAATGATAAACCTTATGGAGTCCTTTCATTC
	AACAGTGTTTTGTTTGAAACGACAGTTATAATTGATGAAGATACAATATCAAGATATGAAGAAATGA
	CAGTGGTTAGAAATGGAGGAACCCATGGGAATGTCTCTCCGAATTGGGTGTTGACACGCAACAGCAC
	TGATCCCTCACCACTAACAGCAGATATCAGACCGAGCTCTGGAGTTCTCCATTTTGCACAACGGCAG
	ATCTTGGCAACAATTCCTCTTACTGTGGTTGATGATGATCTTCCAGAAGAGGCAGAAGCTTATCTAC
	TTCAAATTCTGCCTCATACAATACGAGGAGGTGCAGAAGTGAGCGACCCACCGGAGGATAGTGATGA
	TGTCTATGGCCTAATAACATTTTTTCCTATGGAAAACCAGAAGATTCAAAGCAGCCCAGGTGAACGA
	TACTTATCCTTGAGTTTTACAAGACTAGGAGGGACTAAAGGAGATCTCAGCTTGCTTTATTCTGTAC
	TTTACATTCCTGCTGGAGCTGTGGACCCCTTGCAAGCAAAAGAAGCCATCTTAAATATATCAAGGAG
	AAATGACCTCATTTTTCCAGAGCAAAAAACTCAAGTCACTACAAAATTACCAATAAGAAATGATGCA
	TTCTTTCAAAATGGAGCTCACTTTCTAGTACAGTTGGAAACTGTGCAGTTGTTAAACATAATTCCTC
	TAATCCCACCCATAAGCCCTAGATTTGGGGAAATCTGCAATATTTCTTTACTCGTTACTCCAGCCAT
	TGCAAATGGACAAATTGGCTTTCTCAGCAATCTTCCAATTATTTTGCATGAACCAGAAGATTTTGCT
	GCTGAAGTGGTATACATTCCCTTACATCGGGATGGAACTGATGGCCAGGCTACTGTCTACTGGAGTT
	TGAAGCCCTCTGGCTTTAATTCAAAAGCAGTGACCCCGGATGATATAGGCCCCTTTAATGGCTCTGT
	TTTCTTTTTATCTGGGCAAAGTGACACAACAATCAACATTACTATCAAAGGTGATGACATACCCGAA
	ATGAATGAAACTGTAACACTTTCTCTAGACAGGGTTAACGTGGAAAACCAACTGCTGAAATCTGGAT
	ATACTAGCCGTGACCTAATTATTTTGGAAAATGATCACCCTCGGGGAGTTTTTGAATTTTCTCCTGC
	TTCCAGAGGACCCTATGTTATAAAAGAACGAGAATCTGTAGAGCTCCACATCATCCGATCAAGGGGG
	TCCCTTGTTAAGCAGTTTCTACACTACCGAGTAGAGCCAAGAGATAGCAATGAATTCTATGGAAACA
	CGGGAGTACTAGAATTTAAACCTGGAGAAAGGGAGATAGTGATCACCTTGCTAGCAAGATTCGATGG
	GATACCAGAGTTGGATGAACACTACTGGGTGGTCCTCAGCAGCCACGGAGAACGGGAAAGCAAGTTG
	GGAAGTGCCACCATTGTCAATATAACGATTCTGAAAAATGATCATCCTCATGGCATTATAGAATTTG
	TTTCTGATGGTCTAATTGTGATGATAAATGAAAGCAAAGGACATGCTATCTATAGTGCTGTTTATGA
	TGTAGTAAGAAATCGAGGCAACTTTGGTGATGTTAGTGTATCATGCGTGGTTAGTCCAGACTTTACA
	CAAGATGTATTTCCTGTACAAGGGACTGTTGTCTTTGCAGATCAGCAATTTTCAAAAAATATCACCA
	TTTACTCCCTTCCAGATGAGATTCCAGAAGAAATGGAAGAATTTACCGTTATCCTACTGAATGGCAC
	TGGAGGAGCTAAAGTGGGAAATAGAACAACTGCAACTCTCAGGATTAGAAGAAATGATGACCCCATT
	TATTTTGCACAACCTCGTGTAGTGAGGGTTCACGAAGGTGAGACTGCCAACTTTACAGTTCTCAGAA
	ATCGATCTGTTGATGTGACTTGCATGGTCCAGTATGCTACCAACGATGGGAAGGCTACTGCAAGAGA
	GAGAGATTTCATTCCTGTTGAAAAAGGAGAAACGCTCATTTTTGAGGTTGGAAGTAGACAGCAGAGC
	ATATCCATATTTGTTAATGAAGATGGTATCCCGGAAACAGATGAGCCCTTTTATATAATCCTCTTGA
	ATTCAACAGGTGATACAGTAGTATATCAATATGGAGTAGCTACAGTAATAATTGAAGCTAATGATGA
	CCCAAATGGCATTTTTTCTCTGGAGCCCATAGACAAAGCAGTGCAAGAAGGAAAGACTAATGCATTT
	TGGATTTTGAGGCACCGAGGATACTTTGGTAGTGTTTCTGTATCTTGGCAGCTCTTTCAGAATGATT
	CTGCTTTGCAGCCTGGGCAGGAGTTCTATGAAACTTCAGGAACTGTTAACTTCATGGATGGAGAAGA
	AGCAAAACCAATCATTCTCCATGCTTTTCCAGATAAAATTCCTGAATTCAATGAATTTTATTTCCTA
	AAACTTGTAAACATTTCAGGTCCTGGGGGCCAGCTAGCAGAAACCAACCTCCAGGTGACAGTAATGG
	TTCCATTCAATGATGATCCCTTTGGAGTTTTTATCTTGGATCCAGAGTGTTTAGAGAGAGAAGTGGC
	AGAAGATGTCCTGTCTGAAGATGATATGTCTTATATTACCAACTTCACCATTTTGAGGCAGCAGGGT
	GTGTTTGGTGATGTACAACTGGGCTGGGAAATACTCTCCAGTGAGTTCCCTGCTGGTTTGCCACCAA
	TGATAGATTTTTTACTGGTTGGAATTTTCCCCACCACCGTGCATTTACAACAGCACATGCGGCGTCA
	CCACAGTGGAACGGATGCTTTGTACTTTACCGGACTAGAGCGTGCATTTGGGACTGTTAATCCAAAA
	TACCATCCCTCCAGGAATAATACAATTGCCAACTTTACATTCTCAGCTTGGGTAATGCCCAATGCCA
	ATACGAATGGATTCATTATAGCGAAGGATGACGGTAATGGAAGCATCTACTACGGGGTAAAAATACA
	AACAAACGAATCCCATGTGACACTTTCCCTTCATTATAAAACCTTCGGTTCCAATGCTACATACATT
	GCCAAGACAACAGTCATGAAATATTTAGAAGAAAGTGTTTGGCTTCATCTACTAATTATCCTGGAGG
	ATGGTATAATCGAATTCTACCTGGATGGAAATGCAATGCCCAGGGGAATCAAGAGTCTGAAAGGAGA
	AGCCATTACTGACGGTCCTGGGATACTGAGAATTGGAGCAGCGATAAATGGCAATGACAGATTTACA
	GGTCTGATGCAGGATGTGAGGTCCTATGAGCGGAAACTGACGCTTGAAGAAATTTATGAACTTCATG
	CCATGCCCGCAAAAAGTGATTTACACCCAATTTCTGGATATCTGGAGTTCAGACAGGGAGAAACTAA
	CAAATCATTCATTATTTCTGCAAGAGATGACAATGACGAGGAAGGAGAAGAATTATTCATTCTTAAA
	CTAGTTTCTGTATATGGAGGAGCTCGTATTTCGGAAGAAAATACTACTGCAAGATTAACAATACAAA
	AAAGTGACAATGCAAATGGCTTGTTTGGTTTCACAGGAGCTTGTATACCAGAGATTGCAGAGGAGGG
	ATCAACCATTTCTTGTGTGGTTGAGAGAACCAGAGGAGCTCTGGATTATGTGCATGTTTTTTACACC
	ATTTCACAGATTGAAACTGATGGCATTAATTACCTTGTTGATGACTTTGCTAATGCCAGTGGAACTA
	TTACATTCCTTCCTTGGCAGAGATCAGAGCTTTTGATTGAAGTGTCGCTTCCCATTATTATTTACAA
	CTGTAACTGATACATTAGAATTTGCTTCAAACATGTCTGCTGTAAACCTTTATCAGGTTCTGCAATA
	TATATGTTCTTGATGATGATATTCCTGAACTTAATGAGTATTTCCGTGTGACATTGGTTTCTGCAAT
	TCCTGGAGATGGGAAGCTAGGCTCAACTCCTACCAGTGGTGCAAGCATAGATCCTGAAAAGGAAACC
	ACTGATATCACCATCAAAGCTAGTGATCATCCATATGGCTTGCTGCAGTTCTCCACAGGGCTGCCTC
	CTCAGCCTAAGGACGCAATGACCCTGCCTGCAAGCAGCGTTCCACATATCACTGTGGAGGAGGAAGA
	TGGAGAAATCAGGTTATTGGTCATCCGTGCACAGGGACTTCTGGGAAGGGTGACTGCGGAATTTAGA
	ACAGTGTCCTTGACAGCATTCAGTCCTGAGGATTACCAGAATGTTGCTGGCACATTAGAATTTCAAC
	CAGGACAAAGATATAAATACATTTTCATAAACATCACTGATAATTCTATTCCTGAACTGGAAAAATC
	TTTTAAAGTTGAGTTGTTAAACTTGGAAGGAGGAGCTCTGCTAGATCTATCTACAGATATAACGCTG
	TAAAATCTGGTCCTTTTGGATGATCTATAATGAGTTGATTATTAATAAAAGAAGTCAACAATACCTT
	AAAAAAAAAA
	ORF Start: ATG at 23		ORF Stop: TGA at 4430
	SEQ ID NO: 164	1469 aa	MW at 162809.6 kD
NOV39c,	MVMVTFEVEGGPNPPDEDLSPVKGNITFPPGRATVIYNLTVLDDEVPENDEIFLIQLKSVEGGAEIN
CG150799-03
Protein Sequence	TSRNSIEIIIKKNDSPVRFLQSIYLVPEEDHILIIPVVRGKDNNGNLIGSDEYEVSISYAVTTGNST
	AHAQQNLDFIDLQPNTTVVFPPFIHESHLKFQIVDDTTPEIAESFHIMLLKDTLQGDAVLISPSVVQ
	VTIKPNDKPYGVLSFNSVLFERTVIIDEDRISRYEEITVVRNGGTHGNVSANWVLTRNSTDPSPVTA
	DIRPSSGVLHFAQGQMLATIPLTVVDDDLPEEAEAYLLQILPHTIRGGAEVSEPAEDSDDVYGLITF
	FPMENQKIESSPGERYLSLSFTRLGGTKGDVRLLYSVLYIPAGAVDPLQAKEGILNISRRNDLIFPE
	QKTQVTTKLPXRNDAFFQNGAHFLVQLETVELLNIIPLIPPISFRFGEICNISLLVTPAIANGEIGF
	LSNLPIILHEPEDFAAEVVYIPLHRDGTDGQATVYWSLKPSGFNSKAVTPDDIGPFNGSVLFLSGQS
	DTTINITIKGDDIPEMNETVTLSLDRVNVENQVLKSGYTSRDLIILENDDPGGVFEFSPASRGPYVI
	KEGESVELHIIRSRGSLVKQFLHYRVEPRDSNEFYGNTGVLEFKPGEREIVTTLLARLDGIPELDEH
	YWVVLSSHGERESKLGSATIVNITILKNDDPHGIIEFVSDGLIVMINESKGDAIYSAVYDVVRNRGN
	FGDVSVSWVVSPDFTQDVFPVQGTVVFGDQEFSKNITIYSLPDEIPEEMEEFTVILLNGTGGAKVGN
	RTTATLRIRRNDDPIYFAEPRVVRVQEGETANFTVLRNGSVDVTCMVQYATKDGKATARERDFIPVE
	KGETLIFEVGSRQQSISIFVNEDGIPETDEPFYIILLNSTGRTVVYQYGVATVIIEANDDPNGIFSL
	EPIDKAVEEGKTNAFWILRHRGYFGSVSVSWQLFQNDSALQPGQEFYETSGTVNFMDGEEAXPIILH
	AFPDKIPEFNEFYFLKLVNTSGPGCQLAETNLQVTVMVPFNDDPFGVFILDPECLEREVAEDVLSED
	DMSYITNFTILRQQGVFGDVQLGWEILSSEFPAGLPPMIDFLLVGIFPTTVHLQQHMRRHHSGTDAL
	YFTGLEGAFGTVNPKYHPSRNNTIANFTFSAWVMPNANTNGFIIAKDDGNGSIYYGVKIQTNESHVT
	LSLHYKTLGSNATYIAKTTVMXYLEESVWLHLLIILEDGIIEFYLDGNAMPRGIKSLKGEAITDGPG
	ILRIGAGINGNDRFTGLMQDVRSYERKLTLEEIYELHAMPAKSDLHPISGYLEFRQGETNKSFIISA
	RDDNDEEGEELFILKLVSVYGGARISEENTTARLTIQKSDNANGLFGFTGACIPEIAEEGSTISCVV
	ERTRGALDYVHVFYTISQIETDGINYLVDDFANASGTITFLPWQRSELLIEVSLPIIIYNCN
	SEQ ID NO: 165	8350 bp
NOV39d,	CAGGGAAAAGGGAACCTATGGAATGGTCATGGTGACTTTTGAGGTAGAGGGTGGCCCAAATCCCCCT
CG150799-01
DNA Sequence	GATGAAGATTTGAGTCCAGTTAAAGGAAATATCACCTTTCCCCCTGGCAGACCAACAGTAATTTATA
	ACTTGACAGTACTCGATGACGAGGTACCAGAAAATGATGAAATATTTTTAATTCAACTGAAAAGTGT
	AGAAGGACGAGCTGAGATTAACACCTCTAGGAATTCCATTGAGATCATCATTAAGAAAAATGATAGT
	CCCGTGAGATTCCTTCAGAGTATTTATTTGGTTCCTGAGGAAGACCACATACTCATAATTCCAGTAG
	TTCGTGGAAACGACAACAATCGAAATCTGATTGGATCTGATGAATATGAGGTTTCAATCAGTTATGC
	TCTCACAACTGGGAATTCCACAGCACATGCCCAGCAAAATCTGGACTTCATTGATCTTCAGCCAAAC
	ACAACTGTTGTTTTTCCACCTTTTATTCATGAATCTCACTTGAAATTTCAAATAGTTGATGACACCA
	CACCGGAGATTGCTGAATCGTTTCACATTATGTTACTAAAAGATACCTTACAGGGAGATGCTGTGCT
	AATAAGCCCTTCTGTTGTACAAGTCACCATTAAGCCAAATGATAAACCTTATGGAGTCCTTTCATTC
	AACAGTGTTTTGTTTGAAACGACAGTTATAATTGATGAAGATAGAATATCAAGATATGAAGAAATCA
	CAGTGGTTAGAAATGGAGGAACCCATGGGAATGTCTCTGCGAATTGGGTGTTGACACGGAACAGCAC
	TGATCCCTCACCAGTAACAGCAGATATCAGACCGAGCTCTCGAGTTCTCCATTTTGCACAAGGGCAG
	ATGTTGGCAACAATTCCTCTTACTGTGGTTGATGATGATCTTCCAGAAGAGGCAGAAGCTTATCTAC
	TTCAAATTCTGCCTCATACAATACGAGGAGGTGCAGAAGTGAGCGAGCCAGCGGACGATAGTGATGA
	TGTCTATGGCCTAATAACATTTTTTCCTATGGAAAACCAGAAGATTGAAAGCAGCCCAGGTGAACGA
	TACTTATCCTTGAGTTTTACAAGACTAGGAGGGACTAAAGGAGATGTGAGGTTGCTTTATTCTGTAC
	TTTACATTCCTGCTGCAGCTGTGGACCCCTTGCAAGCAAAAGAAGGCATCTTAAATATATCAAGGAG
	AAATGACCTCATTTTTCCAGAGCAAAAAACTCAAGTCACTACAAAATTACCAATAAGAAATGATGCA
	TTCTTTCAAAATGGAGCTCACTTTCTAGTACAGTTGGAAACTCTGGAGTTGTTAAACATAATTCCTC
	TAATCCCACCCATAAGCCCTAGATTTGGGGAAATCTGCAATATTTCTTTACTGGTTACTCCAGCCAT
	TGCAAATGGAGAAATTCGCTTTCTCAGCAATCTTCCAATTATTTTGCATGAACCAGAAGATTTTGCT
	GCTGAAGTGGTATACATTCCCTTACATCGGGATGGAACTGATGGCCAGGCTACTGTCTACTGGAGTT
	TGAAGCCCTCTGGCTTTAATTCAAAAGCAGTGACCCCGGATGATATAGGCCCCTTTAATGGCTCTGT
	TTTGTTTTTATCTGGGCAAAGTGACACAACAATCAACATTACTATCAAAGGTGATGACATACCGGAA
	ATGAATGAAACTGTAACACTTTCTCTAGACAGGGTTAACGTGGAAAACCAAGTGCTGAAATCTGGAT
	ATACTAGCCGTGACCTAATTATTTTGGAAAATGATGACCCTGGGGGAGTTTTTGAATTTTCTCCTGC
	TTCCAGAGGACCCTATGTTATAAAACAAGGAGAATCTGTAGAGCTCCACATCATCCGATCAAGGGGG
	TCCCTTGTTAAGCAGTTTCTACACTACCGAGTAGAGCCAAGAGATAGCAATGAATTCTATGGAAACA
	CGGGAGTACTAGAATTTAAACCTGGAGAAACCGAGATAGTGATCACCTTGCTAGCAAGATTGGATGG
	GATACCAGAGTTGGATGAACACTACTGGGTGGTCCTCAGCAGCCACGGAGAACGGGAAAGCAAGTTG
	GGAAGTGCCACCATTGTCAATATAACGATTCTGAAAAATGATGATCCTCATGGCATTATAGAATTTC
	TTTCTGATGGTCTAATTGTGATGATAAATGAAAGCAAAGGAGATGCTATCTATAGTGCTGTTTATGA
	TGTAGTAAGAAATCGAGGCAACTTTGGTCATGTTAGTGTATCATGGGTGGTTAGTCCAGACTTTACA
	CAAGATGTATTTCCTGTACAAGGGACTGTTGTCTTTGGAGATCAGGAATTTTCAAAAAATATCACCA
	TTTACTCCCTTCCAGATGAGATTCCAGAAGAAATGGAAGAATTTACCGTTATCCTACTGAATGGCAC
	TGGAGGAGCTAAAGTGGGAAATAGAACAACTGCAACTCTGAGGATTAGAAGAAATGATGACCCCATT
	TATTTTGCAGAACCTCGTGTAGTGAGGGTTCAGGAAGGTGAGACTGCCAACTTTACAGTTCTCAGAA
	ATGGATCTGTTGATGTGACTTGCATGGTCCAGTATGCTACCAAGGATGGGAAGGCTACTGCAAGAGA
	GAGAGATTTCATTCCTGTTGAAAAAGGAGAAACGCTCATTTTTGAGGTTGGAAGTAGACAGCAGAGC
	ATATCCATATTTGTTAATGAAGATGGTATCCCGGAAACACATGAGCCCTTTTATATAATCCTCTTGA
	ATTCAACAGGTGATACAGTAGTATATCAATATGGAGTAGCTACAGTAATAATTGAAGCTAATGATGA
	CCCAAATGGCATTTTTTCTCTGGAGCCCATAGACAAAGCAGTGGAAGAAGGAAAGACTAATGCATTT
	TGGATTTTGAGGCACCGAGGATACTTTGGTAGTGTTTCTGTATCTTGGCAGCTCTTTCAGAATGATT
	CTGCTTTGCAGCCTGGGCAGGAGTTCTATGAAACTTCAGGAACTGTTAACTTCATGGATGGAGAAGA
	AGCAAAACCAATCATTCTCCATCCTTTTCCAGATAAAATTCCTGAATTCAATGAATTTTATTTCCTA
	AAACTTGTAAACATPTCAGGTCCTGGGGGCCAGCTAGCAGAAACCAACCTCCAGGTGACAGTAATGG
	TTCCATTCAATGATGATCCCTTTGGAGTTTTTATCTTGGATCCAGAGTGTTTAGAGAGAGAAGTGGC
	AGAAGATGTCCTGTCTGAAGATGATATGTCTTATATTACCAACTTCACCATTTTGAGGCAGCAGGGT
	GTGTTTGGTGATGTACAACTGGGCTGGGAAATACTGTCCAGTGAGTTCCCTGCTGGTTTGCCACCAA
	TGATAGATTTTTTACTGGTTGCAATTTTCCCCACCACCGTGCATTTACAACAGCACATGCGGCGTCA
	CCACAGTGGAACGGATGCTTTGTACTTTACCGGACTAGAGGGTGCATTTGGGACTGTTAATCCAAAA
	TACCATCCCTCCAGGAATAATACAATTGCCAACTTTACATTCTCAGCTTGGGTAATGCCCAATGCCA
	ATACGAATGGATTCATTATAGCGAACGATGACGGTAATGGAAGCATCTACTACGGGGTAAAAATACA
	AACAAACGAATCCCATGTGACACTTTCCCTTCATTATAAAACCTTGGGTTCCAATGCTACATACATT
	GCCAAGACAACAGTCATGAAATATTTAGAAGAAAGTGTTTGGCTTCATCTACTAATTATCCTGGAGG
	ATGGTATAATCGAATTCTACCTGGATGGAAATGCAATGCCCAGGGGAATCAAGAGTCTGAAAGGAGA
	AGCCATTACTGACGGTCCTGCGATACTGAGAATTGGAGCAGGGATAAATGGCAATGACAGATTTACA
	GGTCTGATGCAGGATGTGAGGTCCTATGAGCGGAAACTGACGCTTGAAGAAATTTATGAACTTCATG
	CCATGCCCGCAAAAAGTGATTTACACCCAATTTCTGGATATCTGGAGTTCAGACAGGGAGAAACTAA
	CAAATCATTCATTATTTCTGCAAGAGATGACAATGACGAGGAAGGAGAAGAATTATTCATTCTTAAA
	CTAGTTTCTGTATATGGAGGAGCTCGTATTTCGGAAGAAAATACTACTGCAAGATTAACAATACAAA
	AAAGTGACAATGCAAATGGCTTGTTTGGTTTCACAGGAGCTTGTATACCAGAGATTGCAGAGGAGGG
	ATCAACCATTTCTTGTGTCGTTGAGAGAACCAGAGGAGCTCTGGATTATGTGCATGTTTTTTACACC
	ATTTCACAGATTGAAACTGATGGCATTAATTACCTTGTTGATGACTTTGCTAATGCCAGTGGAACTA
	TTACATTCCTTCCTTGGCAGAGATCAGAGGTTCTGAATATATATGTTCTTGATGATGATATTCCTGA
	ACTTAATGAGTATTTCCGTGTGACATTGGTTTCTGCAATTCCTGGACATGGGAAGCTAGGCTCAACT
	CCTACCAGTGGTGCAAGCATAGATCCTGAAAAGGAAACGACTGATATCACCATCAAAGCTAGTGATC
	ATCCATATGGCTTGCTGCAGTTCTCCACAGGGCTGCCTCCTCAGCCTAAGGACGCAATCACCCTGCC
	TGCAAGCAGCGTTCCACATATCACTGTGGAGGAGGAAGATGGAGAAATCAGGTTATTGGTCATCCGT
	GCACAGGGACTTCTGGGAAGGGTGACTGCGGAATTTAGAACAGTGTCCTTGACAGCATTCAGTCCTG
	AGGATTACCAGAATGTTGCTGGCACATTAGAATTTCAACCAGGAGAAAGATATAAATACATTTTCAT
	AAACATCACTGATAATTCTATTCCTGAACTGGAAAAATCTTTTAAAGTTGAGTTGTTAAACTTGGAA
	GGACGAGTAGCTGAACTCTTTAGGGTTCATGGAAGTGGTAGTGCCAGTCTAGGAGTGGCTTCCCAAA
	TTCTAGTGACAATTGCAGCCTCTGACCACGCTCATGGCGTATTTGAATTTAGCCCTGAGTCACTCTT
	TGTCAGTGGAACTGAACCAGAAGATGGGTATAGCACTGTTACATTAAATGTTATAAGACATCATGGA
	ACTCTGTCTCCAGTGACTTTGCATTGGAACATAGACTCTGATCCTGATGGTGATCTCGCCTTCACCT
	CTGGCAACATCACATTTGAGATTGGGCAGACGAGCGCCAATATCACTGTGGAGATATTGCCTGACGA
	AGACCCAGAACTGGATAAGGCATTCTCTGTGTCAGTCCTCAGTGTTTCCAGTGGTTCTTTGGGAGCT
	CATATTAATGCCACGTTAACAGTTTTGGCTAGTGATGATCCATATGGGATATTCATTTTTTCTGAGA
	AAAACAGACCTGTTAAAGTTGAGGAAGCAACCCAGAACATCACACTATCAATAATAAGGTTGAAAGG
	CCTCATGGGAAAAGTCCTTGTCTCATATCCAACACTAGATGATATGGAAAAACCACCTTATTTTCCA
	CCTAATTTAGCGAGAGCAACTCAAGGAAGAGACTATATACCAGCTTCTGGATTTGCTCTTTTTGGAG
	CTAATCAGAGTGAGGCAACAATAGCTATTTCAATTTTGGATGATGATGAGCCAGAAAGGTCCGAATC
	TGTCTTTATCGAACTACTCAACTCTACTTTAGTAGCGAAAGTACAGAGTCGTTCAATTCCAAATTCT
	CCACGTCTTGGGCCTAAGGTAGAAACTATTGCGCAACTAATTATCATTGCCAATGATGATGCATTTG
	GAACTCTTCAGCTCTCAGCACCAATTGTCCGAGTGGCAGAAAATCATGTTGGACCCATGATCAATGT
	GACTAGAACAGGAGGAGCATTTGCAGATGTCTCTGTGAAGTTTAAAGCTGTGCCAATAACTGCAATA
	GCTGGTGAAGATTATAGTATAGCTTCATCAGATGTGGTCTTGCTAGAAGGGGAAACCAGTAAAGCCG
	TGCCAATATATGTCATTAATGATATCTATCCTGAACTGGAAGAATCTTTTCTTGTGCAACTGATGAA
	TGAAACAACAGGAGGAGCCAGACTAGGGGCTTTAACACAGGCAGTCATTATTATTGAGGCCTCTGAT
	GACCCCTATGGATTATTTGGTTTTCAGATTACTAAACTTATTGTAGAGGAACCTGAGTTTAACTCAG
	TGAAGGTAAACCTGCCAATAATTCGAAATTCTGGGACACTCGGCAATGTTACTGTTCAGTGGGTTGC
	CACCATTAATGGACAGCTTGCTACTGGCGACCTGCGAGTTGTCTCAGGTAATGTGACCTTTGCCCCT
	GGGGAAACCATTCAAACCTTGTTGTTAGAGGTCCTGGCTGACGACGTTCCGGAGATTGAAGAGGTTA
	TCCAAGTGCAACTAACTGATGCCTCTGGTGCAGGTACTATTGGGTTAGATCGAATTGCAAATATTAT
	TATTCCTGCCAATGATGATCCTTATGGTACAGTAGCCTTTGCTCAGATGGTTTATCGTGTTCAAGAG
	CCTCTGGAAAGAAGTTCCTGTGCTAATATAACTGTCAGGCGAAGCGGAGGCCACTTTGGTCGGCTGT
	TGTTGTTCTACAGTACTTCCGACATTGATGTAGTGGCTCTGGCAATGGAGGAAGGTCAAGATTTACT
	GTCCTACTATGAATCTCCAATTCAAGGGCTGCCTGACCCACTTTGGAGAACTTGGATGAATGTCTCT
	GCCGTGGGGGAGCCCCTGTATACCTGTGCCACTTTGTGCCTTAAGGAACAAGCTTGCTCAGCGTTTT
	CATTTTTCAGTGCTTCTGAGGGTCCCCAGTGTTTCTGGATGACATCATGGATCAGCCCAGCTGTCAA
	CAATTCAGACTTCTGGACCTACAGGAAAAACATGACCAGGGTAGCATCTCTTTTTAGTGGTCAGGCT
	GTGGCTGGGAGTGACTATGAGCCTGTCACAAGGCAATGGGCCATAATGCAGGAAGGTGATGAATTCG
	CAAATCTCACAGTGTCTATTCTTCCTGATGATTTCCCAGAGATGGATGAGAGTTTTCTAATTTCTCT
	CCTTGAAGTTCACCTCATGAACATTTCAGCCAGTTTGAAAAATCAGCCAACCATAGGACAGCCAAAT
	ATTTCTACAGTTGTCATAGCACTAAATGGTGATGCCTTTGGAGTGTTTGTGATCTACAATATTAGTC
	CCAATACTTCCGAAGATGGCTTATTTGTTGAAGTTCAGGAGCAGCCCCAAACCTTGGTGCAGCTGAT
	GATACACAGGACAGGGGGCAGCTTAGGTCAAGTGGCAGTCGAATGGCGTGTTGTTGGTGGAACAGCT
	ACTGAAGGTTTAGATTTTATAGGTGCTGGAGAGATTCTGACCTTTGCTGAAGGTGAAACCAAAAAGA
	CAGTCATTTTAACCATCTTGGATGACTCTGAACCAGAGGATGACGAAAGTATCATAGTTAGTTTGGT
	CTACACTGAAGGTGGAAGTAGAATTTTGCCAAGCTCCCACACTGTTAGAGTGAACATTTTGGCCAAT
	GACAATGTGGCAGGAATTGTTAGCTTTCAGACACCTTCCAGATCTGTCATAGCTCATGAAGGAGAAA
	TTTTACAATTCCATGTGATAAGAACTTTCCCTGGTCGAGGAAATGTTACTGTTAACTGGAAAATTAT
	TGGGCAAAATCTAGAACTCAATTTTGCTAACTTTAGCGGACAACTTTTCTTTCCTGAGGGGTCGTTC
	AATACAACATTGTTTGTGCATTTGTTGGATGACAACATTCCTGAGGAGAAAGAAGTATACCAAGTCA
	TTCTGTATGATGTCAGGACACAAGGAGTTCCACCAGCCCGAATCGCCCTGCTTGATGCTCAAGGATA
	TGCAGCTGTCCTCACAGTAGAAGCCAGTGATGAACCACATGGAGTTTTAAATTTTGCTCTTTCATCA
	AGATTTGTGTTACTACAAGAGGCTAACATAACAATTCAGCTTTTCATCAACAGAGAATTTGGATCTC
	TAGGAGCTATCAATGTCACATATACCACGGTTCCTGGAATGCTGAGTCTGAAGAACCAAACAGTAGG
	AAACCTAGCAGAGCCAGAAGTTGATTTTGTCCCTATCATTGGCTTTCTGATTTTAGAAGAAGGGGAA
	ACAGCAGCAGCCATCAACATTACCATTCTTGAGGATGATGTACCAGAGCTAGAAGAATATTTCCTGG
	TGAATTTAACTTACGTTGGACTTACCATGGCTGCTTCAACTTCATTTCCTCCCAGACTAGGTATGAG
	GGGTTTCTTGTTTGTTTCTTTTTGCTCACTTCAAATGAAATGAAGAAACTTCATTTTTGAATCAGAA
	GTGATCATTGTGCTGTTTTGTTAATCTTAGCTATGTGTTAAA
	ORF Start: ATG at 23		ORF Stop: TGA at 8282
	SEQ ID NO: 166	2753 aa	MW at 301743.8 kD
NOV39d,	MVMVTFEVEGGPNPPDEDLSPVKGNITFPPGRATVIYNLTVLDDEVFENDEIELTQLKSVEGGAEIN
CG150799-01
Protein Sequence	TSRNSIEIIIKKNDSPVRFLQSIYLVPEEDHILIIPVVRGKDNNGNLIGSDEYEVSISYAVTTGNST
	AHAQQNLDFIDLQPNTTVVFPPFIHESHLKFQIVDDTTPEIAESFHIMLLKDTLQGDAVLISPSVVQ
	VTIKPNDKPYGVLSFNSVLFERTVIIDEDRISRYEEITVVRNGGTHGNVSANWVLTRNSTDPSPVTA
	DIRPSSGVLHFAQGQMLATIPLTVVDDDLPEEAEAYLLQILPHTIRGGAEVSEPAEDSDDVYGLITF
	FPMENQKIESSPGERYLSLSFTRLGGTKGDVRLLYSVLYIPAGAVDPLQAKEGILNISRRNDLIFPE
	QKTQVTTKLPIRNDAFFQNGAHFLVQLETVELLNIIPLIPPISPRFGEICNISLLVTPAIANGEIGF
	LSNLPIILHEPEDFAAEVVYIPLHRDGTDGQATVYWSLKPSGFNSKAVTPDDIGPFMGSVLFLSGQS
	DTTINITIKGDDIPFMNETVTLSLDRVNVENQVLKSGYTSRDLIILENDDPGGVFEFSPASRGPYVI
	KEGESVELHIIRSRGSLVKQFLHYRVEPRDSNEFYGNTGVLEFKPGEREIVITLLARLDGIPELDEH
	YWVVLSSHGERESKLGSATIVNITILKNDDFHGIIEFVSDGLIVMINESKGDAIYSAVYDVVRNRGN
	FGDVSVSWVVSPDFTGDVFPVGCTVVFGDGEFSKNITIYSLPDEIPEEMEEFTVILLNGTGGAKVGN
	RTTATLRIRRNDDPIYFAEPRVVRVQEGETANFTVLRNGSVDVTCMVQYATKDGKATARERDFIPVE
	KGETLIFEVGSRQQSISIFVNEDGIPETDEPFYTILLNSTGDTVVYQYGVATVIIEANDDPNGIFSL
	EPIDKAVEEGKTNAFWILRHRGYFGSVSVSWQLFQNDSALQPGQEFYETSGTVNFMDGEEAKPIILH
	AFPDKIPEFNEFYFLKLVNISGPGGQLAETNLQVTVMVPFNDDPFGVFILDPECLEREVAEDVLSED
	DMSYITNFTILRQQGVFGDVQLGWEILSSEFPAGLPFMIDFLLVGIFFTTVHLQQHMRRHHSGTDAL
	YFTGLEGAFGTVNPKYHPSRNNTIANFTFSAWVMPNANTNGFIIAKDDGNCSIYYCVKIQTNESHVT
	LSLHYKTLGSNATYIAKTTVMKYLEESVWLHLLIILEDGIIEFYLDGNAMPRGIKSLRGEAITDGPG
	ILRICAGINGNDRFTGLMQDVRSYERKLTLEEIYELHAMPAKSDLHPISGYLEFRQGETNKSFIISA
	RDDNDEEGEELFILKLVSVYGGARISEENTTARLTIQKSDNANGLFGFTGACIPEIAEEGSTISCVV
	ERTRCALDYVHVFYTISQIETDGINYLVDDFANASGTITFLPWQRSEVLNIYVLDDDIPELNEYFRV
	TLVSAIPGDGKLQSTPTSGASIDPEKETTDITIKASDHPYGLLQFSTGLPFQPKDAMTLPASSVPHI
	TVEEEDGEIRLLVIRAQGLLGRVTAEFRTVSLTAFSPEDYQNVAGTLEFQPCERYKYIFINITDNSI
	FELEKSFKVELLNLEGGVAELFRVDGSGSASLGVASQILVTIAASDHABGVFEFSPESLFVSGTEPE
	DGYSTVTLNVIRHUGTLSPVTLHWNIDSDPDGDLAFTSGNITFEIGQTSANITVEILPDEDPELDKA
	FSVSVLSVSSGSLGAHINATLTVLASDDPYGIFIFSEKNRPVKVEEATQNITLSIIRLKGLMGKVLV
	SYATLDDMEKPPYFPPNLARATQGRDYIPASGFALFGANQSEATIAISILDDDEPERSESVFIELLN
	STLVAKVQSRSIPNSPRLGPKVETIAQLIIIANDDAFGTLQLSAPIVRVAENUVGPIINVTRTGGAF
	ADVSVKFKAVPITAIAGEDYSIASSDVVLLEGETSKAVPIYVINDIYPELEESFLVQLMNETTGGAR
	LGALTEAVIIIEASDDPYGLFGFQITKLIVEEPEFNSVKVNLPIIRNSGTLCNVTVQWVATINGQLA
	TGDLRVVSGNVTFAPGETIQTLLLEVLADDVPEIEEVIQVQLTDASGGGTIGLDRIANIIIPANDDP
	YGTVAFAQMVYRVQEPLERSSCANITVRRSGGHFGRLLLFYSTSDIDVVALAMEECQDLLSYYESPI
	QGVPDPLWRTWMNVSAVGEPLYTCATLCLKEQACSAFSFFSASEGPQCFWMTSWISPAVNNSDFWTY
	RKNNTRVASLFSGQAVAGSDYEPVTRQWAIMQEGDEFANLTVSILPDDFPENDESFLISLLEVHLMN
	ISASLKNQPTIGQPNISTVVIALNGDAFGVFVIYNISFNTSEDCLFVEVQEQPQTLVELMIHRTGGS
	LGQVAVEWRVVGGTATEGLDFIGAGEILTFAEGETKKTVILTILDDSEPEDDESIIVSLVYTEGGSR
	ILPSSDTVRVNILANDNVAGIVSFQTASRSVIGHEGEILQFHVIRTFPGRGNVTVNWKIIGQNLELN
	FANFSGQLFFPEGSLNTTLFVHLLDDNIPEEKEVYQVILYDVRTQGVPPACIALLDAQCYAAVLTVE
	ASDEPHCVLNFALSSRFVLLQEANITIQLFINREFGSLGAINVTYPTVPGMLSLKNQTVGNLAEPEV
	DFVPIIGFLILEEGETAAAINITILEDDVPELEEYFLVNLTYVGLTMAASTSFPPRLGMRGFLFVSF
	CSLQMK

[0549] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 39B.

TABLE 39B
Comparison of NOV39a against NOV39b through NOV39d.
			Identities/
			Similarities for
		NOV39a Residues/	the Matched
	Protein Sequence	Match Residues	Region
	NOV39b	1 . . . 2741	2684/2741 (97%)
		1 . . . 2741	2685/2741 (97%)
	NOV39c	1 . . . 1456	1442/1456 (99%)
		1 . . . 1456	1443/1456 (99%)
	NOV39d	1 . . . 2753	2700/2753 (98%)
		1 . . . 2753	2700/2753 (98%)

[0550] Further analysis of the NOV39a protein yielded the following properties shown in Table 39C.

TABLE 39C
Protein Sequence Properties NOV39a
PSort analysis:   0.5050 probability located in cytoplasm; 0.3836
                  probability located in microbody (peroxisome);
                  0.1851 probability located in lysosome (lumen);
                  0.1000 probability located in mitochondrial
                  matrix space
SignalP analysis: No Known Signal Sequence Predicted

[0551] 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
Geneseq	Protein/Organism/Length	NOV39a Residues/	for the	Expect
Identifier	[Patent #, Date]	Match Residues	Matched Region	Value
AAE10925	Human monogenic	1 . . . 2753	2736/2778 (98%)	0.0
	audiogenic	1 . . . 2777	2739/2778 (98%)
	seizure-susceptible-1
	(mass1) protein - Homo
	sapiens, 2777 aa.
	[WO200165927-A1,
	13 SEP. 2001]
AAE10924	Mouse monogenic	1 . . . 2739	2295/2762 (83%)	0.0
	audiogenic	1 . . . 2761	2516/2762 (91%)
	seizure-susceptible-1
	(mass1) protein - Mus
	musculus, 2780 aa.
	[WO200165927-A1,
	13 SEP. 2001]
AAE10949	Mouse mass1 protein	1 . . . 2049	1710/2072 (82%)	0.0
	mutant (7009deltaG) - Mus	1 . . . 2071	1878/2072 (90%)
	musculus, 2071 aa.
	[WO200165927-A1,
	13 SEP. 2001]
ABG61545	Human transporter and ion	1531 . . . 2288	740/758 (97%)	0.0
	channel, TRICH15, Incyte	1 . . . 746	740/758 (97%)
	ID 7476089CD1 - Homo
	sapiens, 759 aa.
	[WO200240541-A2,
	23 MAY. 2002]
ABB05663	Human signal transduction	2232 . . . 2741	506/510 (99%)	0.0
	protein clone amy2_10p7 -	9 . . . 518	507/510 (99%)
	Homo sapiens, 1615 aa.
	[WO200198454-A2,
	27 DEC. 2001]

[0552] 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
		NOV39a	Identities/
Protein		Residues/	Similarities
Accession		Match	for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
Q8WXG9	Very large G protein-coupled	1 . . . 2741	2721/2766 (98%)	0.0
	receptor 1b - Homo sapiens	180 . . . 2945	2723/2766 (98%)
	(Human), 6307 aa.
Q91ZS2	MASS1 - Mus musculus	1 . . . 2739	2293/2762 (83%)	0.0
	(Mouse), 2780 aa.	1 . . . 2761	2515/2762 (91%)
Q8VHN7	Very large G protein-coupled	1 . . . 2741	2293/2764 (82%)	0.0
	receptor 1 - Mus musculus	179 . . . 2941	2514/2764 (89%)
	(Mouse), 6298 aa.
Q91ZS1	MASS1.2 - Mus musculus	563 . . . 2739	1838/2192 (83%)	0.0
	(Mouse), 2238 aa.	29 . . . 2219	2004/2192 (90%)
Q8TF58	KIAA1943 protein - Homo	234 . . . 1273	1037/1050 (98%)	0.0
	sapiens (Human), 1054 aa	1 . . . 1050	1037/1050 (98%)
	(fragment).

Example 40

[0553] 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: 167	2833 bp
NOV40a,	CAAAGATCCAGTTTGGAAATGAGAGAGGACTAGCATGACACATTGGCTCCACCATTGATATCTCCCA
CG151014-01
DNA Sequence	GAGGTACAGAAACAGGATTCATGAAGATGTTGACAAGACTGCAAGTTCTTACCTTAGCTTTGTTTTC
	AAAGGGATTTTTACTCTCTTTAGGGGACCATAACTTTCTAAGGAGAGAGATTAAAATAGAAGGTGAC
	CTTGTTTTAGGGGGCCTGTTTCCTATTAACGAAAAAGGCACTGGAACTGAAGAATGTGGGCGAATCA
	ATGAAGACCGAGGGATTCAACGCCTGGAAGCCATGTTGTTTGCTATTGATGAAATCAACAAAGATGA
	TTACTTGCTACCAGGAGTGAAGTTGGGTGTTCACATTTTGGATACATGTTCAAGGGATACCTATGCA
	TTGGAGCAATCACTGGAGTTTGTCAGGGCATCTTTGACAAAAGTGGATGAAGCTGAGTATATGTGTC
	CTGATGGATCCTATGCCATTCAAGAAAACATCCCACTTCTCATTGCAGGGGTCATTGGTGGCTCTTA
	TAGCAGTGTTTCCATACAGGTGGCAAACCTGCTGCGGCTCTTCCAGATCCCTCAGATCAGCTACGCA
	TCCACCACCGCCAAACTCAGTGATAAGTCGCGCTATGATTACTTTGCCAGGACCGTGCCCCCCGACT
	TCTACCAGGCCAAAGCCATGGCTGAGATCTTGCGCTTCTTCAACTGGACCTACGTGTCCACAGTAGC
	CTCCGAGGGTGATTACGGGGAGACAGGGATCGAGGCCTTCGAGCAGGAAGCCCGCCTGCGCAACATC
	TGCATCGCTACGGCGGAGAAGGTGGGCCGCTCCAACATCCGCAAGTCCTACGACAGCGTGATCCGAG
	AACTGTTGCACAAGCCCAACGCGCGCGTCGTGGTCCTCTTCATCCGCAGCGACGACTCGCGGGAGCT
	CATTGCAGCCGCCAGCCGCGCCAATGCCTCCTTCACCTGGGTGGCCAGCGACGGCTGGGGCGCGCAG
	GAGAGCATCATCAAGGGCAGCGAGCATGTGGCCTACGGCGCCATCACCCTGGAGCTGGCCTCCCAGC
	CTGTCCGCCAGTTCGACCGCTACTTCCAGAGCCTCAACCCCTACAACAACCACCGCAACCCCTGGTT
	CCGGGACTTCTGGGAGCAAAAGTTTCAGTGCAGCCTCCAGAACAAACGCAACCACAGGCGCGTCTGC
	GACAAGCACCTGGCCATCGACAGCAGCAACTACGAGCAAGAGTCCAAGATCATGTTTGTGGTGAACG
	CGGTGTATGCCATGGCCCACGCTTTGCACAAAATGCAGCGCACCCTCTGTCCCAACACTACCAAGCT
	TTGTGATGCTATGAAGATCCTGGATGGGAAGAAGTTCTACAAGGATTACTTGCTGAAAATCAACTTC
	ACGGCTCCATTCAACCCAAATAAAGATGCAGATAGCATAGTCAAGTTTGACACTTTTGGAGATGGAA
	TGGGGCGATACAACGTGTTCAATTTCCAAAATGTAGGTGGAAAGTATTCCTACTTGAAAGTTGGTCA
	CTGGGCAGAAACCTTATCGCTAGATGTCAACTCTATCCACTGGTCCCCGAACTCAGTCCCCACTTCC
	CAGTGCAGCGACCCCTGTGCCCCCAATGAAATGAAGAATATGCAACCAGGGGATGTCTGCTGCTGGA
	TTTGCATCCCCTGTGAACCCTACGAATACCTGGCTGATGAGTTTACCTGTATGGATTGTGGGTCTGG
	ACAGTGGCCCACTGCAGACCTAACTGGATGCTATGACCTTCCTGAGGACTACATCAGGTGGGAAGAC
	GCCTGGGCCATTGGCCCAGTCACCATTGCCTGTCTGGGTTTTATGTGTACATGCATGGTTGTAACTG
	TTTTTATCAAGCACAACAACACACCCTTGGTCAAAGCATCCGGCCGAGAACTCTGCTACATCTTATT
	GTTTGGGGTTGGCCTGTCATACTGCATGACATTCTTCTTCATTGCCAAGCCATCACCAGTCATCTGT
	GCATTGCGCCGACTCGGGCTGGGGAGTTCCTTCGCTATCTGTTACTCAGCCCTGCTGACCAAGACAA
	ACTGCATTGCCCGCATCTTCGATGGGGTCAAGAATGGCGCTCAGAGGCCAAAATTCATCAGCCCCAG
	TTCTCAGGTTTTCATCTGCCTGGGTCTGATCCTGGTGCAAATTGTGATGGTGTCTGTGTGGCTCATC
	CTGCAGGCCCCAGGCACCAGGAGGTATACCCTTACAGAGAAGCGGGAAACAGTCATCCTAAAATGCA
	ATGTCAAAGATTCCAGCATGTTGATCTCTCTTACCTACGATGTGATCCTGGTGATCTTATGCACTGT
	GTACGCCTTCAAAACGCGGAAGTGCCCAGAAAATTTCAACGAAGCTAAGTTCATAGGTTTTACCATG
	TACACCACGTGCATCATCTGGTTGGCCTTCCTCCCTATATTTTATGTGACATCAAGTGACTACAGAC
	CTCTGCAAGCACGTATGTGTCAACGGTGTGCAATGGGCGGGAAGTCCTCGACTCCACCACCTCATCT
	CTGTGATTGTGAATTGCAGTTCAGTTCTTGTGTTTTTAGACTGTTAGACAAAAGTGCTCACGTGCAG
	CTCCAGAATATGGAAACAGAGCAAAAGAACAACCCTAGTACCTTTTTTTAGAAACAGTACGATAAAT
	TATTTTTGAGGACTGTATATAGTGATGTGCTAGAACTTTCTAGGCTGAGTCTAGTGCCCCTATTATT
	AACAATTCCCCCAGAACATGGAAATAACCATTGTTTACAGAGCTCAGCATTGGTGACAGGGTCTGAC
	ATGGTCAGTCTACTTCAAG
	ORF Start: ATG at 88		ORF Stop: TAG at 2662
	SEQ ID NO: 168	858 aa	MW at 96975.6 kD
NOV40a,	MKMLTRLQVLTLALFSKGFLLSLGDHNFLRREIKIEGDLVLGGLFPINEKGTGTEECGRTNEDRGIQ
CG151014-01
Protein Sequence	RLEAMLFAIDEINKDDYLLPGVKLGVHTLDTCSRDTYALEQSLEFVRASLTKVDEAEYMCPDGSYAI
	QENIPLLIAGVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSRYDYFARTVPPDFYQAKAM
	AEILRFFNWTYVSTVASEGDYGETGIEAFEQEARLRNICIATAEKVGRSNIRKSYDSVIRELLQKPN
	ARVVVLFNRSDDSRELIAAASRANASFTWVASDGWGAQESIIKGSEHVAYGAITLELASQPVRQFDR
	YFQSLNPYNNHRNPWFRDFWEQKFQCSLQNKRNHRRVCDKHLAIDSSNYEQESKIMFVVNAVYAMAH
	ALHKMQRTLCPNTTKLCDAMKILDGKKLYKDYLLKINFTAPFNPNKDADSIVKFDTFGDGMGRYNVF
	NFQNVGGKYSYLKVGHWAETLSLDVNSIHWSRNSVFTSQCSDPCAPNEMXNMQPGDVCCWICIPCEP
	YEYLADEFTCMDCGSGQWPTADLTGCYDLPEDYIRWEDAWAIGPVTIACLGFMCTCMVVTVEIKHNN
	TPLVKASGRELCYILLFGVGLSYCMTFFFIAKPSPVICALRRLGLGSSFAICYSALLTKTNCIARIF
	DGVKNGAQRPKFISPSSQVFICLGLILVQIVNVSVWLILEAPGTRRYTLTEKRETVILKCNVKDSSM
	LISLTYDVILVILCTVYAFKTRKCPENFNEAXFIGFTMYTTCIIWLAFLPIFYVTSSDYRPLQARMC
	QRCAMGGKSSTPPPHLCDCELQFSSCVFRLLDKSAHVQLQNMETEQKNNPSTFF
	SEQ ID NO: 169	1758 bp
NOV40b,	CAAAGATCCAGTTTGGAAATGAGAGAGGACTAGCATGACACATTGGCTCCACCATTGATATCTCCCA
CG151014-02
DNA Sequence	GAGGTACAGAAACAGGATTCATGAAGATGTTGACAAGACTGCAAGTTCTTACCTTAGCTTTGTTTTC
	AAAGGGATTTTTACTCTCTTTAGGGGACCATAACTTTCTAAGGAGAGAGATTAAAATAGAAGGTGAC
	CTTGTTTTAGGGGGCCTGTTTCCTATTAACGAAAAAGGCACTGGAACTGAAGAATGTGGGCGAATCA
	ATGAAGACCGAGGGATTCAACGCCTGGAAGCCATGTTGTTTGCTATTGATGAAATCAACAAAGATGA
	TTACTTGCTACCAGGAGTGAAGTTGGGTGTTCACATTTTGGATACATGTTCAACGGATACCTATGCA
	TTGGAGCAATCACTGGAGTTTGTCAGGGCATCTTTGACAAAAGTGGATGAAGCTGAGTATATGTGTC
	CTGATGGATCCTATGCCATTCAAGAAAACATCCCACTTCTCATTGCAGGGGTCATTGGTGGCTCTTA
	TAGCAGTGTTTCCATACAGGTGGCAAACCTGCTGCGGCTCTTCCAGATCCCTCAGATCAGCTACGCA
	TCCACCAGCGCCAAACTCAGTGATAAGTCGCGCTATGATTACTTTGCCAGGACCGTGCCCCCCGACT
	TCTACCAGGCCAAAGCCATGGCTGAGATCTTGCGCTTCTTCAACTGGACCTACGTGTCCACAGTAGC
	CTCCGAGGGTGATTACGGGGAGACAGGGATCGAGGCCTTCGAGCAGGAAGCCCGCCTGCGCAACATC
	TGCATCGCTACGGCGGAGAAGGTGGGCCGCTCCAACATCCGCAAGTCCTACGACAGCGTGATCCGAG
	AACTGTTGCAGAAGCCCAACGCGCGCGTCGTCGTCCTCTTCATCCGCAGCGACGACTCGCGGGAGCT
	CATTGCAGCCGCCAGCCGCGCCAATGCCTCCTTCACCTGGGTGCCCAGCGACGGCTGCGGCGCGCAG
	GAGAGCATCATCAAGGGCAGCGAGCATGTGGCCTACGGCCCCATCACCCTGGAGCTGGCCTCCCAGC
	CTGTCCGCCAGTTCGACCCCTACTTCCAGAGCCTCAACCCCTACAACAACCACCGCAACCCCTGGTT
	CCGGGACTTCTGCGAGCAAAAGTTTCACTGCAGCCTCCAGAACAAACGCAACCACAGGCGCGTCTGC
	GACAAGCACCTGGCCATCGACAGCAGCAACTACGAGCAAGAGTCCAAGATCATGTTTGTGGTGAACG
	CGGTGTATGCCATCGCCCACGCTTTGCACAAAATGCAGCGCACCCTCTGTCCCAACACTACCAAGCT
	TTGTGATGCTATGAAGATCCTGGATGGGAAGAAGTTGTACAAGGATTACTTGCTGAAAATCAACTTC
	ACGGGTGCAGACGACAACCATGTGCATCTCCGTCAGCCTGAGTGGCTTTCTGGTCTTGGGCTGTTTG
	TTTGCACCCAAGGTTCACATCATCCTGTTTCAACCCCAGAAGAATGTTGTCACACACAGACTGCACC
	TCAACAGGTTCAGTGTCAGTGGAACTGGGACCACATACTCTCAGTCCTCTGCAAGCACGTATGTGCC
	AACGGTGTGCAATGGGCGGGAAGTCCTCGACTCCACCACCTCATCTCTGTGATTGTGAATTGCAGTT
	CAGTTCTTGTGTTTTTAGACTGTTAGACAAAAGTGCTCACGTGCACCTCCAGAATATGGAAACAGAG
	CAAAAGAACAACCCTA
	ORF Start: ATG at 88		ORF Stop: TAG at 1699
	SEQ ID NO: 170	537 aa	MW at 60801.8 kD
NOV40b,	MKMLTRLQVLTLALFSKGELLSLGDHNFLRREIKIEGDLVLGGLFPINEKGTGTEECGRINEDRGIQ
CG151014-02
Protein Sequence	RLEAMLFAIDEINKDDYLLPGVKLGVHILDTCSRDTYALEQSLEFVRASLTKVDEAEYMCPDGSYAI
	QENIPLLIAGVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSRYDYFARTVPPDFYQAKAM
	AEILRFFNWTYVSTVASEGDYGETGIEAFEQEARLRNICIATAEKVGRSNIRKSYDSVIRELLQKPN
	ARVVVLFMRSDDSRELIAAASRANASFTWVASDGWGAQESIIKGSEHVAYGAITLELASQPVRQFDR
	YFQSLNPYNNHRNPWFRDFWEQKFQCSLQNKRNHRRVCDKHLAIDSSNYEQESKIMFVVNAVYAMAH
	ALHKMQRTLCPNTTKLCDAMKILDGKKLYKDYLLKINFTGADDNHVHLRQPEWLCGLGLFVCTQGSH
	HPVSTPEECCHTQTAFQQVQCQWNWDHILSVLCKHVCANGVQWAGSPRLHHLISVIVNCSSVLVFLD
	C
	SEQ ID NO: 171	1758 bp
NOV40c,	CCTTGATCCAGTTTCCAAATGAGAGAGGACTAGCATGACACATTGGCTCCACCATTGATATCTCCCA
CG151014-03
DNA Sequence	CAGGTACAGAAACAGGATTCATGAAGATGTTGACAAGACTGCAAGTTCTTACCTTAGCTTTGTTTTC
	AAAGGGATTTTTACTCTCTTTAGGGGACCATAACTTTCTAAGGAGAGACATTAAAATAGAAGGTGAC
	CTTGTTTTAGGGGGCCTGTTTCCTATTAACGAAAAAGGCACTGGAACTGAAGAATGTGGGCGAATCA
	ATGAAGACCGAGGGATTCAACGCCTGGAAGCCATGTTGTTTGCTATTGATGAAATCAACAAAGATGA
	TTACTTGCTACCAGGAGTGAAGTTGGGTGTTCACATTTTGGATACATGTTCAAGGGATACCTATGCA
	TTGCAGCAATCACTGGAGTTTGTCAGGGCATCTTTGACAAAAGTGGATGAAGCTGAGTATATGTGTC
	CTGATGGATCCTATGCCATTCAAGAAAACATCCCACTTCTCATTGCAGGGGTCATTGGTGGCTCTTA
	TAGCAGTGTTTCCATACAGGTGGCAAACCTGCTGCGGCTCTTCCAGATCCCTCAGATCAGCTACGCA
	TCCACCAGCGCCAAACTCAGTGATAAGTCGCGCTATGATTACTTTGCCAGGACCGTGCCCCCCGACT
	TCTACCAGGCCAAACCCATGGCTGAGATCTTGCGCTTCTTCAACTGGACCTACGTGTCCACAGTAGC
	CTCCGAGGGTGATTACGGGCAGACAGGGATCGAGGCCTTCGAGCAGGAAGCCCGCCTGCGCAACATC
	TGCATCGCTACGGCGGAGAAGGTGGGCCGCTCCAACATCCGCAAGTCCTACGACAGCGTGATCCGAG
	AACTGTTGCAGAAGCCCAACGCGCGCGTCGTGGTCCTCTTCATGCGCAGCGACGACTCGCGGGAGCT
	CATTGCAGCCGCCAGCCGCGCCAATGCCTCCTTCACCTGGGTGGCCAGCGACGCCTGGGGCGCGCAG
	GAGACCATCATCAAGGGCAGCGAGCATGTGGCCTACGGCGCCATCACCCTGGAGCTGGCCTCCCAGC
	CTGTCCGCCAGTTCGACCGCTACTTCCAGAGCCTCAACCCCTACAACAACCACCGCAACCCCTGGTT
	CCGGGACTTCTGGGAGCAAAAGTTTCAGTGCAGCCTCCAGAACAAACGCAACCACAGGCGCGTCTGC
	GACAAGCACCTGGCCATCGACAGCAGCAACTACGAGCAAGAGTCCAAGATCATGTTTGTGGTGAACG
	CGGTGPATGCCATGGCCCACGCTTTGCACAAAATGCAGCCCACCCTCTGTCCCAACACTACCAAGCT
	TTGTGATGCTATGAAGATCCTGGATGGGAAGAAGTTGTACAAGGATTACTTGCTGAAAATCAACTTC
	ACGGGTGCAGACGACAACCATGTGCATCTCCGTCAGCCTGAGTGGCTTTGTGGTCTTGGGCTGTTTG
	TTTCCACCCAAGGTTCACATCATCCTGTTTCAACCCCAGAAGAATGTTGTCACACACAGACTGCACC
	TCAACAGGTTCAGTGTCAGTGGAACTGGGACCACATACTCTCAGTCCTCTGCAAGCACGTATGTGCC
	AACGGTGTGCAATGGGCGGGAAGTCCTCGACTCCACCACCTCATCTCTGTGATTGTGAATTGCAGTT
	CAGTTCTTGTGTTTTTAGACTGTTAGACAAAAGTGCTCACGTGCAGCTCCACAATATGGAAACAGAG
	CAAAAGAACAACCCTA
	ORF Start: ATG at 88		ORF Stop: TAG at 1699
	SEQ ID NO: 172	537 aa	MW at 60801.8kD
NOV40c,	MKMLTRLQVLTLALFSKCFLLSLGDHNFLRREIKIEGDLVLGGLFPINEKGTGTEECGRINEDRGIQ
CG151014-03
Protein Sequence	RLEAMLFAIDEINKDDYLLPGVKLGVHTLDTCSRDTYALEQSLEFVRASLTKVDEAEYMCPDGSYAI
	QENIPLLIAGVIGGSYSSVSIQVANLLRLFQIPQISYASTSAKLSDKSRYDYFARTVPPDFYQAXAN
	AEILRFFNWTYVSTVASEGDYGETGIEAFEQEARLRNICIATAEKVGRSNIRKSYDSVIRELLQKPN
	ARVVVLFMRSDDSRELIAAASRANASFTWVASDGWGAQESIIKGSEHVAYGAITLELASQPVRQFDR
	YFQSLNPYNNHRNPWFRDFWEQKFQCSLQNKRNHRRVCDKHLAIDSSNYEQESKIMFVVNAVYAMAH
	ALHKMQRTLCPNTTKLCDAMKILDGKKLYKDYLLKINFTGADDNHVHLRQPEWLCGLGLFVCTQGSH
	HPVSTPEECCHTQTAPQQVQCQWNWDHILSVLCKHVCANGVQWAGSPRLHHLISVIVNCSSVLVFLD
	C

[0554] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 40B.

TABLE 40B
Comparison of NOV40a against NOV40b and NOV40c.
			Identities/
		NOV40a Residues/	Similarities for
	Protein Sequence	Match Residues	the Matched Region
	NOV40b	1 . . . 441	409/441 (92%)
		1 . . . 441	409/441 (92%)
	NOV40c	1 . . . 441	409/441 (92%)
		1 . . . 441	409/441 (92%)

[0555] Further analysis of the NOV40a protein yielded the following properties shown in Table 40C.

TABLE 40C
Protein Sequence Properties NOV40a
PSort     0.6400 probability located in plasma membrane; 0.4600
analysis: probability located inGolgi body; 0.3700 probability
          located in endoplasmic reticulum (membrane);0.1000
          probability located in endoplasmic reticulum (lumen)
SignalP   Cleavage site between residues 25 and 26
analysis:

[0556] 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
			Identities/
			Similarities for
Geneseq	Protein/Organism/Length	NOV40a Residues/	the Matched	Expect
Identifier	[Patent #, Date]	Match Residues	Region	Value
AAE15990	Human glutamate receptor,	3 . . . 811	797/809 (98%)	0.0
	metabotrophic 3 (GRM3)	1 . . . 809	799/809 (98%)
	protein - Homo sapiens, 877
	aa. [WO200196350-A2,
	20 DEC. 2001]
AAR82657	Human mGluR3 - Homo	3 . . . 811	797/809 (98%)	0.0
	sapiens, 877 aa.	1 . . . 809	799/809 (98%)
	[WO9522609-A2,
	24 AUG. 1995]
AAM23698	Human EST encoded protein	1 . . . 811	796/811 (98%)	0.0
	SEQ ID NO: 1223 - Homo	1 . . . 811	798/811 (98%)
	sapiens, 857 aa.
	[WO200154477-A2,
	02 AUG. 2001]
AAR64252	Human mGluR3 - Homo	1 . . . 811	796/811 (98%)	0.0
	sapiens, 879 aa.	1 . . . 811	799/811 (98%)
	[WO9429449-A,
	22 DEC. 1994]
AAO15105	Human	21 . . . 811	777/791 (98%)	0.0
	ph2SPMGluR3-CaR*AAA*	17 . . . 807	781/791 (98%)
	Gqi5 fusion construct protein
	sequence - Chimeric - Homo
	sapiens, 1402 aa.
	[WO200229033-A2,
	11 APR. 2002]

[0557] 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
			Identities/
Protein			Similarities for
Accession		NOV40a Residues/	the Matched	Expect
Number	Protein/Organism/Length	Match Residues	Portion	Value
Q14832	Metabotropic glutamate	3 . . . 811	797/809 (98%)	0.0
	receptor 3 precursor	1 . . . 809	799/809 (98%)
	(mGluR3) - Homo sapiens
	(Human), 877 aa.
Q8TBH9	Glutamate receptor,	3 . . . 811	795/809 (98%)	0.0
	metabotropic 3 - Homo	1 . . . 809	797/809 (98%)
	sapiens (Human), 877 aa.
Q9QYS2	Metabotropic glutamate	1 . . . 811	773/811 (95%)	0.0
	receptor 3 protein - Mus	1 . . . 811	792/811 (97%)
	musculus (Mouse), 879 aa.
P31422	Metabotropic glutamate	1 . . . 811	772/811 (95%)	0.0
	receptor 3 precursor - Rattus	1 . . . 811	790/811 (97%)
	norvegicus (Rat), 879 aa.
JC7160	metabotropic glutamate	1 . . . 811	771/811 (95%)	0.0
	receptor subtype 3 precursor -	1 . . . 811	790/811 (97%)
	mouse, 879 aa.

[0558] PFam analysis predicts that the NOV40a protein contains the domains shown in the Table 40F.

TABLE 40F
Domain Analysis of NOV40a
		Identities/
		Similarities
	NOV40a Match	for the	Expect
Pfam Domain	Region	Matched Region	Value
ANF_receptor	58 . . . 489	194/473 (41%)	3.2e−173
		399/473 (84%)
7tm_3	576 . . . 820	109/283 (39%)	3.1e−104
		217/283 (77%)

Example 41

[0559] 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: 173	880 bp
NOV41a,	GAATTCTGATGTGCTTCAGTCCACAGAACAGTAACACATGAGCTGCTTTTGGGGAGAGCTTGAGTAC
CG151297-01
DNA Sequence	TCAGTCGGAGCATCATCATGGGGTCTAGTGCCACAGAGATTGAAGAATTGGAAAACACCACTTTTAA
	GTATCTTACAGGAGAACAGACTCAAAAAATGTGGCAGCGCCTGAAAGGAATACTAAGATGCTTGGTG
	AAGCAGCTGGAAAGAGGTGATGTTAACGTCGTCGACTTAAAGAAGAATATTGAATATGCGGCATCTG
	TGCTGGAAGCAGTTTATATCGATGAAACAAGAAGACTTCTGGATACTGAAGATGAGCTCAGTGACAT
	TCAGACTGACTCAGTCCCATCTGAAGTCCGGGACTCGTTGGCTTCTACCTTTACACGGAAAATGGGG
	ATGACAAAAAAGAAACCTGAGGAAAAACCAAAATTTCGGAGCATTGTGCATGCTGTTCAAGCTGGAA
	TTTTTGTGGAAAGAATGTACCGAAAAACATTTTCTCTTCTGACAGACTCAACAGAGAAAATTGTTAT
	TCCTCTTATAGAGGAAGCCTCAAAAGCCGAAACTTCTTCCTATGTGGCAAGCAGCTCAACCACCATT
	GTGGGGTTACACATTGCTGATGCACTAAGACGATCAAATACAAAAGGCTCCATGAGTGATGGGTCCT
	ATTCCCCAGACTACTCCCTTGCAGCAGTGGACCTGAAGAGTTTCAAGAACAACCTGGTGGACATCAT
	TCAGCAGAACAAAGAGAGGTGGAAAGAGTTAGCTGCACAAGAAGCAAGAACCAGTTCACAGAAGTGT
	GAGTTTATTCATCAGTAAACACCTTTAAGTAAAACCTCGTGCATGGTGGCAGCTCTAATTTGACCAA
	AAGACTTGG
	ORF Start: ATG at 85		ORF Stop: TAA at 820
	SEQ ID NO: 174	245 aa	MW at 27787.2 kD
NOV41a,	MGSSATEIEELENTTFKYLTGEQTEKMWQRLKGILRCLVKQLERGDVNVVDLKKNIEYAASVLEAVY
CG151297-01
Protein Sequence	IDETRRLLDTEDELSDIQTDSVPSEVRDWLASTFTRKMGMTKKKPEEKPKFRSIVHAVQAGIFVERN
	YRKTFSLLTDSTEKIVIPLIEEASKAETSSYVASSSTTIVGLHIADALRRSNTKGSMSDGSYSPDYS
	LAAVDLKSFKNNLVDIIQQNKERWKELAAQEARTSSQKCEFIHQ
	SEQ ID NO: 175	1817 bp
NOV41b,	TCAGTGCACAGAACAGTAACAGATGAGCTGCTTTTGGCGAGAGCTTGAGTACTCAGTCGGTCAGTAG
CG151297-02
DNA Sequence	TACAGTAGCAGGCTCACATGTACGGATTGTTCTTGTGAGGAGCATCATCATGGGGTCTAGTGCCACA
	GAGATTGAAGAATTGGAAAACACCACTTTTAAGTATCTTACAGGAGAACAGACTGAAAAAATGTGGC
	AGCGCCTGAAAGGAATACTAAGATGCTTGGTGAAGCAGCTGGAAACACGTGATGTTAACGTCGTCGA
	CTTAAAGAAGAATATTGAATATGCGGCATCTGTGCTGGAAGCAGTTTATATCGATGAAACAAGAAGA
	CTTCTGGATACTGAAGATGACCTCAGTGACATTCAGACTGACTCAGTCCCATCTGAAGTCCGGGACT
	GGTTGGCTTCTACCTTTACACGGAAAATGGGGATGACAAAAAAGAAACCTGAGGAAAAACCAAAATT
	TCGGAGCATTGTGCATGCTGTTCAAGCTGGAATTTTTGTGGAAAGAATGTACCGAAAAACATATCAT
	ATGGTTGGTTTGGCATATCCAGCAGCTGTCATCGTAACATTAAAGGATGTTGATAAATGGTCTTTCG
	ATGTATTTGCCCTAAATGAAGCAAGTGGAGAGCATAGTCTGAAGTTTATGATTTATGAACTGTTTAC
	CAGATATGATCTTATCAACCGTTTCAAGATTCCTGTTTCTTGCCTAATCACCTTTGCAGAAGCTTTA
	GAAGTTGGTTACGGCAAGTACAAAAATCCATATCACAATTTGATTCATGCAGCTGATGTCACTCAAA
	CTGTGCATTACATAATGCTTCATACAGGTATCATGCACTGGCTCACTGAACTGGAAATTTTAGCAAT
	GGTCTTTGCTGCTGCCATTCATGATTATGAGCATACAGCGACAACAAACAACTTTCACATTCAGACA
	AGGTCAGATGTTGCCATTTTGTATAATCATCGCTCTGTCCTTGAGAATCACCACGTGAGTGCAGCTT
	ATCGACTTATGCAAGAAGAAGAAATGAATATCTTGATAAATTTATCCAAAGATCACTGGAGGGATCT
	TCGGAACCTAGTGATTGAAATGGTTTTATCTACAGACATGTCAGGTCACTTCCAGCAAATTAAAAAT
	ATAAGAAACAGTTTGCAGCAGCCTGAAGGGATTGACAGAGCCAAAACCATGTCCCTGATTCTCCACG
	CAGCAGACATCAGCCACCCAGCCAAATCCTGGAAGCTGCATTATCGGTGGACCATGGCCCTAATGGA
	GGAGTTTTTCCTGCAGGGAGATAAAGAAGCTGAATTAGGGCTTCCATTTTCCCCACTTTGTGATCGG
	AAGTCAACCATGGTGGCCCAGTCACAAATAGGTTTCATCGATTTCATAGTAGAGCCAACATTTTCTC
	TTCTGACAGACTCAACAGAGAAAATTCTTATTCCTCTTATAGAGGAAGCCTCAAAAGCCGAAACTTC
	TTCCTATGTGGCAAGCAGCTCAACCACCATTGTGGGGTTACACATTGCTGATGCACTAAGACGATCA
	AATACAAAAGGCTCCATGAGTGATGGGTCCTATTCCCCAGACTACTCCCTTGCAGCAGTGGACCTGA
	AGAGTTTCAAGAACAACCTGGTGGACATCATTCAGCAGAACAAAGAGAGGTGGAAACAGTTAGTTGC
	ACAAGAAGCAAGAACCAGTTCACAGAAGTGTGAGTTTATTCATCAGTAAACACCTTTAAGTAAAACC
	TCGTGCATGGTGGCAGCTCTAATTTGACCAAAAGACTTGGAGATTTTGATTATGCTTGCTGGATATC
	TATTCTGT
	ORF Start: ATG at 117		ORF Stop: TAA at 1722
	SEQ ID NO: 176	535 aa	MW at 61249.3 kD
NOV41b,	MGSSATEIEELENTTFKYLTGEQTEKMWQRLKGILRCLVKQLERGDVNVVDLKKNIEYAASVLEAVY
CG151297-02
Protein Sequence	IDETRRLLDTEDELSDIQTDSVPSEVRDWLASTFTRKMGMTKKKPEEKPKFRSIVHAVQAGIFVERM
	YRKTYHMVGLAYPAAVIVTLKDVDKWSFDVFALNEASGEHSLKFMIYELFTRYDLINRFKIPVSCLI
	TFAEALEVGYGKYKNPYHNLIHAADVTQTVHYIMLHTGIMHWLTELEILAMVFAAAIHDYEHTGTTN
	NFHIQTRSDVAILYNDRSVLENHHVSAAYRLMQEEEMNILINLSKDDWRDLRNLVIEMVLSTDMSGH
	FQQIKNIRNSLQQPEGIDRAKTMSLTLHAADISHPAKSWKLHYRWTMALMEEFFLQGDKEAELGLPF
	SPLCDRKSTMVAQSQIGFIDFIVEPTFSLLTDSTEKIVIPLIEEASKAETSSYVASSSTTIVGLHIA
	DALRRSNTKGSMSDGSYSPDYSLAAVDLKSFKNNLVDIIQQNKERWKELVAQEARTSSQKCEFIHQ

[0560] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 41B.

TABLE 41B
Comparison of NOV41a against NOV41b.
		Identities/
Protein	NOV41a Residues/	Similarities for
Sequence	Match Residues	the Matched Region
NOV41b	1 . . . 159	141/159 (88%)
	1 . . . 159	148/159 (92%)

[0561] Further analysis of the NOV41a protein yielded the following properties shown in Table 41C.

TABLE 41C
Protein Sequence Properties NOV41a
PSort     0.8800 probability located in nucleus; 0.1000 probability
analysis: located inmitochondrial matrix space; 0.1000 probability
          located in lysosome (lumen);0.1000 probability located
          in plasma membrane
SignalP   No Known Signal Sequence Predicted
analysis:

[0562] 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
			Identities/
			Similarities for
Geneseq	Protein/Organism/Length	NOV41a Residues/	the Matched	Expect
Identifier	[Patent #, Date]	Match Residues	Region	Value
AAB85116	Human 3′, 5′ cyclic	1 . . . 159	141/159 (88%)	5e−75
	nucleotide phosphodiesterase	1 . . . 159	148/159 (92%)
	(HSPDE1A3A) - Homo
	sapiens, 535 aa.
	[EP1097707-A1,
	09 MAY 2001]
AAB85105	Human 3′, 5′ cyclic	1 . . . 159	141/159 (88%)	5e−75
	nucleotide phosphodiesterase	1 . . . 159	148/159 (92%)
	(HSPDE1A3A) - Homo
	sapiens, 535 aa.
	[EP1097706-A1,
	09 MAY 2001]
AAE07953	Human phosphodiesterase	1 . . . 159	141/159 (88%)	5e−75
	(PDE) type 1 protein - Homo	1 . . . 159	148/159 (92%)
	sapiens, 535 aa.
	[EP1097719-A1,
	09 MAY 2001]
AAE07917	Human phosphodiesterase	1 . . . 159	141/159 (88%)	5e−75
	(PDE) type 1 protein - Homo	1 . . . 159	148/159 (92%)
	sapiens, 535 aa.
	[EP1097718-A1,
	09 MAY 2001]
AAY80988	Human 61 kD CaM-PDE	1 . . . 159	141/159 (88%)	5e−75
	(clone pHcam61-6N-7), SEQ	1 . . . 159	148/159 (92%)
	ID NO: 49 - Homo sapiens,
	535 aa. [US6015677-A,
	18 JAN. 2000]

[0563] In a BLAST search of public sequence datbases, the NOV41a protein was found to have homology to the proteins shown in the BLASTP data in Table 41E.

TABLE 41E
Public BLASTP Results for NOV41a
			Identities/
Protein			Similarities for
Accession		NOV41a Residues/	the Matched	Expect
Number	Protein/Organism/Length	Match Residues	Portion	Value
AAH22480	Hypothetical 62.3 kDa protein -	1 . . . 159	141/159 (88%)	1e−74
	Homo sapiens (Human), 545	1 . . . 159	148/159 (92%)
	aa.
P54750	Calcium/calmodulin-dependent	2 . . . 159	140/158 (88%)	6e−74
	3′,5′-cyclic nucleotide	1 . . . 158	147/158 (92%)
	phosphodiesterase 1A (EC
	3.1.4.17) (Cam-PDE 1A) (61
	kDa Cam-PDE) (hCam-1) -
	Homo sapiens (Human), 534
	aa.
Q9EPR9	Phosphodiesterase 1A - Rattus	1 . . . 159	134/159 (84%)	6e−71
	norvegicus (Rat), 542 aa.	1 . . . 159	144/159 (90%)
Q61481	Calcium/calmodulin-dependent	1 . . . 159	133/159 (83%)	3e−70
	3′,5′-cyclic nucleotide	21 . . . 179	143/159 (89%)
	phosphodiesterase 1A (EC
	3.1.4.17) (Cam-PDE 1A) (61
	kDa Cam-PDE) - Mus
	musculus (Mouse), 565 aa.
A45334	3′,5′-cyclic-nucleotide	1 . . . 159	129/159 (81%)	6e−69
	phosphodiesterase (EC	1 . . . 159	144/159 (90%)
	3.1.4.17) 1A,
	calmodulin-dependent, 61K
	brain form - bovine, 530 aa.

[0564] PFam analysis predicts that the NOV41a protein contains the domains shown in the Table 41F.

TABLE 41F
Domain Analysis of NOV41a
			Identities/
		NOV41a	Similarities
	Pfam	Match	for the Matched	Expect
	Domain	Region	Region	Value
	PDEase	138 . . . 159	9/49 (18%)	0.11
			22/49 (45%)

Example 42

[0565] 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: 177	512 bp
NOV42a,	CCATGGCGGGCTGCGCGGCGCGGGCTCCGCCGGGCTCTGAGGCGCGTCTCAGCCTCGCCACCTTCCT
CG151822-01
DNA Sequence	GCTGGGCGCCTCGGTGCTCGCGCTGCCGCTGCTCACGCGCGCCGGCCTGCAGGGCCGCACCGGGCTG
	GCGCTCTACGTGGCCGGGCTCAACGCGCTGCTGCTGCTGCTCTATCGCCCGCCTCGCTACCAGATAG
	CCATCCGAGCTTGTTTCCTGGGGTTTGTGTTCGGCTGCGGCACGCTGCTAAGTTTTAGCCAGTCTTC
	TTGGAGTCACTTTGGCTGAACTGAAGCAGATTACCTGGCTCAGTGTCACACGGCTGCTGATGGTGGT
	CTTCGGAGAATGTCTGAGGAAGGCCGCCATGTNTACAGCTGGCTCCAATTTCAACCACGTGGTACAG
	AATGAAAAATCAGATACACATACTCTGGTGACCAGTGGAGTGTACGCTTGGTTTCGGCATCCTTCTT
	ACGTCGGGTGGTTTTACTGGAGTATTGGAACTCAGGTGATGCT
	ORF Start: ATG at 3		ORF Stop: TGA at 285
	SEQ ID NO: 17	894 aa	MW at 9871.5 kD
NOV42a,	MAGCAARAPPGSEARLSLATFLLGASVLALPLLTRAGLQGRTGLALYVAGLNALLLLLYRPPRYQIA
CG151822-01
Protein Sequence	IRACFLGFVFGCGTLLSFSQSSWSHFG
	SEQ ID NO: 179	3597 bp
NOV42b,	GGCACGAGCGGCGCCGCCGCCCGCTAGTCCGCCCCCCGGCGCCATGGCGGGCTGCGCGGCGCGGGCT
CG151822-02
DNA Sequence	CCGCCGGGCTCTGAGGCGCGTCTCAGCCTCGCCACCTTCCTGCTGGGCGCCTCGGTGCTCGCCCTGC
	CGCTGCTCACGCGCGCCGGCCTGCAGGGCCGCACCGGGCTGGCGCTCTACGTGGCCGGGCTCAACGC
	GCTGCTGCTGCTGCTCTATCGGCCGCCTCGCTACCAGATAGCCATCCGAGCTTGTTTCCTGGGGTTT
	GTGTTCGGCTGCGGCACGCTGCTAAGTTTTAGCCAGTCTTCTTGGAGTCACTTTGGCTGGTACATGT
	GCTCCCTGTCATTGTTCCACTATTCTGAATACTTGGTGACACCAGTCAATAATCCCAAAAGTCTGTC
	CTTGGATTCCTTTCTCCTGAATCACAGCCTGGAGTATACAGTAGCTGCTCTTTCTTCTTGGTTAGAG
	TTCACACTTGAAAATATCTTTTGGCCAGAACTGAAGCAGATTACCTGGCTCAGTGTCACAGGGCTGC
	TGATGGTGGTCTTCGGAGAATGTCTGAGGAAGGCCGCCATGTTTACAGCTGGCTCCAATTTCAACCA
	CGTGGTACAGAATGAAAAATCAGATACACATACTCTGGTGACCAGTGGAGTGTACGCTTGGTTTCGG
	CATCCTTCTTACGTCGGGTGGTTTTACTGGAGTATTGGAACTCAGGTGATGCTGTGTAACCCCATCT
	GCGGCGTCAGCTATGCCCTGACAGTGTGGCGATTCTTCCGCGATCGAACAGAAGAAGAAGAAATCTC
	ACTAATTCACTTTTTTGGAGAGGAGTACCTGCAGTATAAGAAGAGGGTGCCCACCGGCCTCCCTTTC
	ATAAAGGGGGTCAAGGTGGACCTGTGACGGGCAGTGGCCCCGGTGACCTTGGGGCCTCCGACCCTGT
	GCAGCCTGGGACAAAACTGTTTCCGGTTGGCCGCTCCCACATGGATTTTCTTAATCGTTTTATGTCA
	TTAGTCACTCTTCTGGAATGTCACTCAAGACCAAGCGGTCAGAAGGCCTGAGGACCCAAGGCCCCAC
	TGGAGCAGTCTGTCCTTATGCCGAATCAAGGCGGAACATGGGTGAAAGACGAGTAAGGGGCAAATCA
	CAGCAATATTCCACAGCGCCCTCCAGAGTTACCTGGGGAGGACCGAGGCCACACGCCACTGCCCCCG
	AGGCCAGAGTGTAAGTAAAGGATAACCAGGACTCGCTCGGAGAGATGGACTCTGTCCTCAGCAACAC
	TCCACAGCAGAAAGGGGTAGCAGGTACCCCTTCTTATCAGCGGTAAAAATGCATTTACAACCTTTCA
	TTTAACCGAAAAACACAGACCGCTTTAACCTCTTTATTTCTGTCCCCCACTGCATGAACATCTATAC
	AATTTTAAAAATACTTCCTCATAGGATGCTTTGGCCCTTCATCTATTTAATCATAGCTACATACCTA
	TTTTTTTATAAGTAGCAGTACACATTCAAAGGGGTATTCCTAGCTCAATGCTTGGTGTTCTAGTTCA
	ACTTTTATCCTGCAGCAAGTAAGCCTAGATAACTCTACACGATTTCGCTGAGTGGCTTTGTGTGACC
	GTGGCCCCAGGCCAAGGGGACCATGGCCCTGGCTGGCTTTCCCCCGGGGGTCTCAGCTCCTGTTGTC
	AGTGATAGGCGGCTCAAAGGAGCATCAGTTTCTTTTGATCCAAGAAGTGCTTACTGAATGCCTGCCC
	TGTGCGTGGCCTTAAACATTGAGAAGTCCTGCTCTCCGTTTATTTGGGATTTGATTCTCATTTTACC
	ATACCTTATATTCTCAATTTCAATGCCAGTCTCAGAACTCTTGTTTTCTGTGTTCTGTTCTCAAAAT
	TACATTGTCCCTCATGTCATTTCAAACTGTTTTCCAAAGGGATTTGAGCATATACAACTACAAATCC
	AAGCAGATTGACTCTCAAAAATAATCTTAAATACTGCAAATAGTCCCAACTAAGATTCAGTCAGTAT
	GTTTGTTTTGCAAGTTTCGGAGAGTAAGTTGGCTTTGAGTCACACATCGAAGCTTTAAGAGGTGAGA
	CGCTGGCTTCATTCTGGACTAGACAGGAACTTGGCCTCAGCGTGAGATCCTGCCATCCAGTGTTGCG
	GTGGCACTGAAGAAGTGTGAATGTGAAGGCGGCGTCGGCGCGGGGCCAGAGCACCACTCTGCTGCCC
	CACCACGCGGCCTGTGAGGAGCCACTAAACCTTTCCGTCCCTAGACCTCCCCATCTGTGGAATGGCG
	TCAATACCACCTACCTCACAGGGGTGTTGTGAGGACTGAGAAGAACAATGTCAAATGTTTTTAATAC
	TCAGATGTGGGAGCGACATCAATGAAATCTGTACTGTATGAAAGCTACACAAAAATGGGCAGACATT
	TGGTTAATTGTGCCAGATACCTAAAATGTATGTTCAGAAAAGCATTTTATCAACTCAGAAATATGAC
	TTATTTCTAGATTCATGGCTTAATGAATTTTTTCATTGTTATATATACCAAAGAGGCTTACGGGTTC
	ATTGATTGGTTTGAAAACCAGACAGACGGCCGGCCACGCCTGTAATCCCAAAGTGCTGGGATTGCAG
	CGTGAGCCACCACGCCCAGCCAAGATGAACTCCTTAAGGACAGGATTTGGTAAGTGATTGACTTCTT
	TTTAGTTCCATGATCTTGAGATTATTTTTAGCTTTATAAATTTAGCAGTGGCAGGGCCCGTGGAGAA
	TCAGGTTAATCAGGTAAAGCCTTTCTCGGTATTTGCTGCCAAGGCCACATCACCAATTTTCTCGATT
	TAAAAAACTGTCAAGAGATTTATTTTTCCATTGCACGTTTTAAAGTGGAGATTCTGAAGTGGAAAAT
	AGGTACTGTCAGAACAAAGCTACCTGGAAACAGCATAGAGTGAAGCCTTTCGTGAGGGCTTGCAGGC
	CGCTGCTGAGTGGCAGTTTACAGAAGAGGTCGCGGGGTGAGCCTCTTAGCAGGACAGAAAACAAGGC
	AGCAGCGCACCTGCCACCCCTTCACGAGCTGCTCCTTCAGCCTAAAAAGTAGGCTTTATTCATCCCT
	TCTGTTCATTTACCAACCTGGGGGATTGATACGACCGGGGAAAATGTTCCTAAACCAGGAAGCTGCG
	TTAGCCCATCAGGCTTTGTAAGATCTCGCCAACAGCTACCTGCTTAGGAGTACCCCCACGATACGCA
	CAGCACACCACTGTCCCTTCACTGCACTTTCTTCCTGCCTTAGGTAGTTGGGCTTGCCCACCCTAGT
	TTGCTTTTGTAGTGGTTTGGCAAGGTTAGAAGGCCTCGGCCTCTCTGTCATGCTGGGAAGTGCCTAC
	TCTCTGGGCCACTGCTGCAGAGGCCGTGGCACTTGTCATGGGTTTGGAAGACCCAGCCATCTGCAGC
	AGAGGCAGCCTATCCCATTGCAAGGAGAGGAACTGAACGGAGTAATTATTCPACTCTTCTTTTTACA
	TAAATGTTTATTTAAATATTCTAAATTGGATTTTCATTCACAGATACTGATTATTCTTTCCAGTTCT
	TAAATAAAACTGCACTTGATTTCACTCAAAAAAAAAAAAAAAAAAA
	ORF Start: ATG at 44		ORF Stop: TGA at 896
	SEQ ID NO: 180	284 aa	MW at 31937.7 kD
NOV42b,	MAGCAARAPPGSEARLSLATFLLGASVLALPLLTRAGLQGRTGLALYVAGLNALLLLLYRPPRYQIA
CG151822-02
Protein Sequecne	IRACFLGFVFGCGTLLSFSQSSWSHFGWYMCSLSLFHYSEYLVTAVNNPKSLSLDSFLLNHSLEYTV
	AALSSWLEFTLENIFWPELKQITWLSVTGLLMVVFGECLRKAAMFTAGSNFNHVVQNEKSDTHTLVT
	SGVYAWFRHPSYVGWFYWSIGTQVMLCNPICGVSYALTVWRFERDRTEEEEISLIHFFGEEYLEYKK
	RVPTGLPFIKGVKVDL

[0566] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 42B.

TABLE 4
2B Comparison of NOV42a against NOV42b.
		Identities/
	NOV42a Residues/	Similarities for
Protein Sequence	Match Residues	the Matched Region
NOV42b	1 . . . 94	67/94 (71%)
	1 . . . 94	67/94 (71%)

[0567] Further analysis of the NOV42a protein yielded the following properties shown in Table 42C.

TABLE 42C
Protein Sequence Properties NOV42a
PSort     0.6000 probability located in plasma membrane; 0.4000
analysis: probability located in Golgi body; 0.3174 probability
          located in mitochondrial intermembrane space; 0.3000
          probability located in endoplasmic reticulum (membrane)
SignalP   Cleavage site between residues 37 and 38
analysis:

[0568] 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
			Identities/
			Similarities for
Geneseq	Protein/Organism/Length	NOV42a Residues/	the Matched	Expect
Identifier	[Patent #, Date]	Match Residues	Region	Value
AAY32299	Farnesyl-directed cysteine	1 . . . 94	94/94 (100%)	2e−48
	carboxymethyltransferase	1 . . . 94	94/94 (100%)
	STE14 - Homo sapiens, 284
	aa. [WO9955878-A1,
	04 NOV. 1999]
AAW67730	Human prenylcysteine	1 . . . 94	94/94 (100%)	2e−48
	carboxyl methyltransferase -	1 . . . 94	94/94 (100%)
	Homo sapiens 284 aa
	[WO9856924-A1,
	17 DEC. 1998]
AAB32052	Human secreted protein	12 . . . 94	83/83 (100%)	3e−41
	BLAST search protein SEQ	1 . . . 83	83/83 (100%)
	ID NO: 110 - Homo sapiens,
	223 aa. [WO200058350-A1,
	05 OCT. 2000]
AAB32051	Human secreted protein	12 . . . 94	83/83 (100%)	3e−41
	BLAST search protein SEQ	1 . . . 83	83/83 (100%)
	ID NO: 109 - Homo sapiens,
	223 aa. [WO200058350-A1,
	05 OCT. 2000]
AAY32300	Mouse farnesyl-directed	5 . . . 94	82/90 (91%)	2e−40
	cysteine	4 . . . 93	83/90 (92%)
	carboxymethyltransferase -
	Mus musculus, 153 aa.
	[WO9955878-A1,
	04 NOV. 1999]

[0569] 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
			Identities/
Protein			Similarities for
Accession		NOV42a Residues/	the Matched	Expect
Number	Protein/Organism/Length	Match Residues	Portion	Value
O60725	Protein-S isoprenylcysteine	1 . . . 94	94/94 (100%)	5e−48
	O-methyltransferase (EC	1 . . . 94	94/94 (100%)
	2.1.1.100) (Isoprenylcysteine
	carboxylmethyltransferase)
	(Prenylcysteine carboxyl
	methyltransferase) (pcCMT)
	(Prenylated protein carboxyl
	methyltransferase) (PPMT) -
	Homo sapiens (Human), 284
	aa.
Q9EQK7	Protein-S isoprenylcysteine	5 . . . 94	84/90 (93%)	2e−41
	O-methyltransferase (EC	4 . . . 93	85/90 (94%)
	2.1.1.100) (Isoprenylcysteine
	carboxylmethyltransferase)
	(Prenylcysteine carboxyl
	methyltransferase) (pcCMT)
	(Prenylated protein carboxyl
	methyltransferase) (PPMT) -
	Mus musculus (Mouse), 283
	aa.
O12947	Protein-S isoprenylcysteine	13 . . . 94	49/90 (54%)	2e−19
	O-methyltransferase (EC	9 . . . 98	59/90 (65%)
	2.1.1.100) (Isoprenylcysteine
	carboxylmethyltransferase)
	(Prenylcysteine carboxyl
	methyltransferase) (pcCMT)
	(Prenylated protein carboxyl
	methyltransferase) (PPMT)
	(Farnesyl cysteine carboxyl
	methyltransferase) (FCMT) -
	Xenopus laevis (African
	clawed frog), 288 aa.
Q9WVM4	Protein-S isoprenylcysteine	53 . . . 94	39/42 (92%)	8e−17
	O-methyltransferase (EC	1 . . . 42	40/42 (94%)
	2.1.1.100) (Isoprenylcysteine
	carboxylmethyltransferase)
	(Prenylcysteine carboxyl
	methyltransferase) (pcCMT)
	(Prenylated protein carboxyl
	methyltransferase) (PPMT)
	(Farnesyl cysteine carboxyl
	methyltransferase) (FCMT) -
	Rattus norvegicus (Rat), 232
	aa (fragment).
Q9R1L8	Farnesyl cysteine carboxyl	65 . . . 94	28/30 (93%)	4e−10
	methyltransferase - Rattus	1 . . . 30	29/30 (96%)
	norvegicus (Rat), 33 aa
	(fragment).

Example 43

[0570] The NOV43 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 43A.

TABLE 43A
NOV43 Sequence Analysis
	SEQ ID NO: 181	2306 bp
NOV43a,	GCCATGGCGTCCTGCGTGGGGAGCCGGACCCTAAGCAAGGATCATGTGAACTACAAAATGCATTTCC
CG152256-01
DNA Sequence	CGATGATCAACGAGCAGCAAGTGGAGGACATCACCATTGACTTCTTCTACCGGCCGCATACCATCAC
	GACAACATCTGGAGAGGCATCCTCTCTGTTATTTTCTTCTTTCTTATCATCAGTGTGTTAGCTTTCC
	CTCTTCTTCATGCATCTCCTCCCCAATTTTCCCGAGTGCTGGTGGGATCAAGTCATTCTGGACATCC
	TGTTGTGCAATGGCGGTGGCATTTGGCTGGGCATGGTCGTTTGCCGGTTTTTAGAGATGAGGACTTA
	CCACTGGGCAAGCTTCAAGGACATTCATACCACCACCGGGAAGATCAAGAGAGCTGTTCTGCAGTTC
	ACTCCTGCTAGCTGGACCTATGTTCGATGGTTTGACCCCAAATCTTCTTTTCAGAGAGTAGCTGGAG
	TGTACCTTTTCATGATCATCTGGCAGCTGACTGAGTTGAATACCTTCTTCTTGAAGCATATCTTTGT
	GTTCCAAGCCAGTCATCCATTAAGTTCGGGTAGAATTCTCTTTATTGGTGGCATCACAGCTCCCACA
	GTGAGACAGTACTACGCTTACCTCACCGACACACAGTGCAACCGCGTAGGAACACAATGCTGGGTGT
	TTCGGGCTTTCACCACTTTCCTCTCTCTGTACGGCATGATTTGGTATGCAGAACACTATGGTCACCG
	AGAAAAGACCTACTCGGAGTGTGAAGATGGCACCTACAGTCCAGAGATCTCCTGGCATCACAGGAAA
	CGGACAAAAGGTTCTGAAGACAGCCCACCCAAGCATGCAGGCAACAACGAAAGCCATTCTTCCAGGA
	GAAGGAATCGGCATTCCAAGTCAAAAGTCACCAATGGCGTTGGAAAGAAATGAAAAACCCTGGTTAA
	TCAAAGATGTTCCAGAGTGCCTAGAACTCAGAGGGAAATGGAACTCATTTGGAACTCCCCGTGAGGA
	GGTCGAGGCGCACAGGGCAAGCAGCAAGAGGCGAGGGCACTTGGGGGTCATTATTTGAGATCGTAAG
	TCTTGTTTCCCACAGACCTGGCCGCGTCAGGCAGATCATCGCCTGGGCGGCCTTTGCCAACGTGGGG
	TCTCTTCTAACTTCAGCACTTGACATGCGGTCACCGGTGCCAGCGCGGTGTGTTGAAGGGAAACGGT
	AGCTATTCATTCACAGTTGCCAAGAGCACCTCCGCGCCTGCTGGATCGTGGATGCAGCGTAAACATC
	TTCCTTCAGACGAGGCATTAACCCCATGGTTAATGGACTGGTCACCAGTTTTTATTTTATTTTTATG
	AATCTACCTTTCCATTGATTGATTTAAGTTCAGGCCACTTTTCTGTCTTTTATTTGGTTACTGTTGT
	TATTTGTTTTTAAGTTAGGATGCTTTTTAACAGCCTTTAGAAGCCGCTGCTGAAATTGATACTGGGG
	GAAGGGTTCCCCTTCCTTCTAGAGCAGAAAAGGGAGAGAAGTGTTGTATTCCTGTTTGGTAACCTCA
	GTCTCCTGTAAGACCTCCTACCACATGGCGAGTATACACCAATCAGGAGAGGGTAGCTGCCTGCATA
	GGAGCCTCGCTTCCGATTATTCCCTTCCCAATATTATTCATCCAGACTTACCCACAGTGCACAAAAG
	CAAACCTGCTAGAGAGGCAGTGAACACCACAGCTTCTCCCCAGCTTGGTGCCTTTTACATCGGGTTT
	GTTCTCCTTCCATGGTGTGTTGCTGACATTGTCACTGAGTCCCATGTGACGTGCTGGTGAGTATTAC
	CTTTCATCTGTGCCATGCTCTAGAACCTTGACCTTGATAGTTCACCACGTCTGATGGATCCCTGTTT
	TAAATAAAAACGATTCACTTTAAAGCCT
	ORF Start: ATG at 4		ORF Stop: TGA at 1324
	SEQ ID NO: 182	440 aa	MW at 51772.5 kD
NOV43a,	MASCVGSRTLSKDDVNYKMHFRMTNEQQVEDITIDFFYRPHTITLLSPTTVSLMYFAFTRDDSVPED
CG152256-01
Protein Sequence	NIWRGILSVIFFFLIISVLAFPNGPFTRPHPALWRMVFGLSVLYFLFLVFLLFLNFEQVKSLMYWLD
	PNLRYATREADVMEYAVNCHVITWERIISHFDIFAFGHFWGWAMKALLIRSYGLCWTISITWELTEL
	FFMHLLPNFAECWWDQVILDILLCNGGGIWLGMVVCRFLEMRTYHWASFKDIHTTTGKIKRAVLQFT
	PASWTYVRWFDPKSSFQRVAGVYLFMIIWQLTELNTFFLKHIFVFQASHPLSWGRILFIGGITAPTV
	RQYYAYLTDTQCKRVGTQCWVFGAFTTFLCLYGMTWYAEHYGNREKTYSECEDGTYSPEISWHHRKG
	TKGSEDSPPKHAGNNESHSSRRRNRHSKSKVTNGVGKK

[0571] Further analysis of the NOV43a protein yielded the following properties shown in Table 43B.

TABLE 43B
Protein Sequence Properties NOV43a
PSort analysis:   0.6000 probability located in plasma membrane;
                  0.4000 probability located in Golgi body;
                  0.3000 probability located in endoplasmic
                  reticulum (membrane); 0.0300 probability
                  located in mitochondrial inner membrane
SignalP analysis: No Known Signal Sequence Predicted

[0572] A search of the NOV43a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 43C.

TABLE 43C
Geneseq Results for NOV43a
			Identities/
			Similarities
Geneseq	Protein/Organism/Length	NOV43a Residues/	for the	Expect
Identifier	[Patent #, Date]	Match Residues	Matched Region	Value
ABB89640	Human polypeptide	1 . . . 440	440/473 (93%)	0.0
	SEQ ID NO 2016 -	1 . . . 473	440/473 (93%)
	Homo sapiens, 473
	aa. [WO200190304-A2,
	29 NOV. 2001]
AAB58945	Breast and ovarian cancer	1 . . . 440	439/473 (92%)	0.0
	associated antigen protein	44 . . . 516	439/473 (92%)
	sequence SEQ ID 653 -
	Homo sapiens, 516 aa.
	[WO200055173-A1,
	21 SEP. 2000]
ABB71324	Drosophila melanogaster	3 . . . 359	206/357 (57%)	e−133
	polypeptide SEQ ID NO	59 . . . 412	276/357 (76%)
	40764 - Drosophila
	melanogaster, 498 aa.
	[WO200171042-A2,
	27 SEP. 2001]
AAB73515	Human transferase HTFS-22,	22 . . . 361	128/351 (36%)	2e−60
	SEQ ID NO: 22 - Homo	45 . . . 389	185/351 (52%)
	sapiens, 487 aa.
	[WO200132888-A2,
	10 MAY 2001]
AAM79907	Human protein SEQ ID NO	22 . . . 361	128/351 (36%)	2e−60
	3553 - Homo sapiens, 529 aa.	63 . . . 407	185/351 (52%)
	[WO200157190-A2,
	09 AUG. 2001]

[0573] In a BLAST search of public sequence datbases, the NOV43a protein was found to have homology to the proteins shown in the BLASTP data in Table 43D.

TABLE 43D
Public BLASTP Results for NOV43a
			Identities/
Protein			Similarities for
Accession		NOV43a Residues/	the Matched	Expect
Number	Protein/Organism/Length	Match Residues	Portion	Value
P48651	Phosphatidylserine synthase I	1 . . . 440	440/473 (93%)	0.0
	(Serine-exchange enzyme I)	1 . . . 473	440/473 (93%)
	(EC 2.7.8.-) - Homo sapiens
	(Human), 473 aa.
Q99LH2	Similar to phosphatidylserine	1 . . . 440	428/473 (90%)	0.0
	synthase 1 - Mus musculus	1 . . . 473	437/473 (91%)
	(Mouse), 473 aa.
Q00576	Phosphatidylserine synthase I	1 . . . 440	428/473 (90%)	0.0
	(Serine-exchange enzyme I)	1 . . . 471	434/473 (91%)
	(EC 2.7.8.-) - Cricetulus
	longicaudatus (Long-tailed
	hamster) (Chinese hamster),
	471 aa.
O55024	Phosphatidylserine synthase-	1 . . . 440	421/473 (89%)	0.0
	1 - Mus musculus (Mouse), 473	1 . . . 473	432/473 (91%)
	aa.
Q9BSY0	Similar to phosphatidylserine	145 . . . 440	292/329 (88%)	e−178
	synthase 1 - Homo sapiens	6 . . . 334	293/329 (88%)
	(Human), 334 aa (fragment).

[0574] PFam analysis predicts that the NOV43a protein contains the domains shown in the Table 43E.

TABLE 43E
Domain Analysis of NOV43a
		Identities/
	NOV43a	Similarities
	Match	for the
Pfam Domain	Region	Matched Region	Expect Value
COLFI	119 . . . 137	10/19 (53%)	0.12
		14/19 (74%)
PSS	96 . . . 370	179/310 (58%)	1.1e−206
		267/310 (86%)

Example 44

[0575] The NOV44 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 44A.

TABLE 44A
NOV44 Sequence Analysis
	SEQ ID NO: 183	1151 bp
NOV44a,	CNTGNATTTGGCCGCGGGGCCATGTAGCTCCGAGCGGCGGATCGCGAGCCTCCTGCGAACCCCAGCC
CG171804-01
DNA Sequence	TGCACGCCCGGTTAGCATTCCGCCGGGAGATGCGGCAGTGGAATCTGGAAGGGCGGTGAAAAACCTA
	CGTCCTGCCCTCGCCCGGCCTCTCCATTCGTCCCCCGGGTAGAGAGGGTCGGCTCGTGCTCATCATC
	CTGTGCTCCGTGGTCTTCTCTGCCCTCTACATCCTCCTGTGCTGCTGGGCCGGCCTGCCCCTCTGCC
	TGGCCACCTGCCTGGACCACCACTTCCCCACAGGCTCCAGGCCCACTGTGCCGGGACCCCTGCACTT
	CAGTGGATATAGCAGTGTGCCAGATGGCAAGCCGCTGGTCCGCGAGCCCTGCCGCAGCTGTGCCGTG
	GTGTCCAGCTCCGGCCAAATGCTGGGCTCAGGCCTGGGTGCTGAGATCGACAGTGCCGAGTGCGTGT
	TCCGCATGAACCAGGCGCCCACCGTGGGCTTTGAGGCGGATGTCGGCCAGCGCAGCACCCTGCGTGT
	CGTCTCACACACAAGCGTGCCGCTGCTGCTGCGCAACTATTCACACTACTTCCAGAAGGCCCGAGAC
	ACGCTCTACATGGTGTGGGGCCAGGGCAGGCACATGGACCGGGTGCTCGGCGGCCGCACCTACCGCA
	CGCTGCTGCAGCTCACCAGGATGTACCCCGGCCTGCAGGTGTACACCTTCACGGAGCGCATGATGGC
	CTACTGCGACCAGATCTTCCAGGACGAGACGGGCAAGAACCGGAGGCAGTCGGGCTCCTTCCTCAGC
	ACCGGCTGGTTCACCATGATCCTCGCGCTGGAGCTGTGTGAGGAGATCGTGGTCTATGGGATGGTCA
	GCGACAGCTACTGCAGGGAGAAGAGCCACCCCTCAGTGCCTTACCACTACTTTGAGAAGGGCCGGCT
	AGATGAGTGTCAGATGTACCTGGCACACGAGCAGGCGCCCCGAACCCCCCACCGCTTCATCACTGAG
	AAGGCGGTCTTCTCCCGCTGGGCCAAGAAGAGGCCCATCGTGTTCGCCCATCCGTCCTGGAGGACTG
	AGTAGCTTCCGTCGTCCTGCCAGCCGCCATGCCGTTCCGAGGCCTCCGGGATGTCCCATCCCAAGCC
	ATCACACTCCAC
	ORF Start: ATG at 421		ORF Stop: TAG at 1075
	SEQ ID NO: 184	218 aa	MW at 25333.8 kD
NOV44a,	MLGSGLGAEIDSAECVFRMNQAPTVGFEADVGQRSTLRVVSHTSVPLLLRNYSHYFQKARDTLYMVW
CG171804-01
Protein Sequence	GQGRHMDRVLGGRTYRTLLQLTRMYPGLQVYTFTERMMAYCDQIFQDETGKNRRQSGSFLSTGWFTM
	ILALELCEEIVVYGMVSDSYCREKSEPSVPYHYFEKGRLDECQMYLAHEQAPRSAHRFITEKAVFSR
	WAKKRPIVFAHPSWRTE

[0576] Further analysis of the NOV44a protein yielded the following properties shown in Table 44B.

TABLE 44B
Protein Sequence Properties NOV44a
PSort analysis:   0.6400 probability located in microbody (peroxisome);
                  0.3000 probability located in nucleus; 0.2068
                  probability located in lysosome (lumen); 0.1000
                  probability located in mitochondrial matrix space
SignalP analysis: No Known Signal Sequence Predicted

[0577] A search of the NOV44a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 44C.

TABLE 44C
Geneseq Results for NOV44a
			Identities/
			Similarities
Geneseq	Protein/Organism/Length	NOV44a Residues/	for the	Expect
Identifier	[Patent #, Date]	Match Residues	Matched Region	Value
AAB75350	Human secreted protein #9 -	1 . . . 218	218/218 (100%)	e−128
	Homo sapiens, 302 aa.	85 . . . 302	218/218 (100%)
	[WO200100806-A2,
	04 JAN. 2001]
AAB61614	Human protein HP03380 -	1 . . . 218	218/218 (100%)	e−128
	Homo sapiens, 302 aa.	85 . . . 302	218/218 (100%)
	[WO200102563-A2,
	11 JAN. 2001]
AAB25764	Human secreted protein SEQ	1 . . . 218	218/218 (100%)	e−128
	ID #76 - Homo sapiens, 302	85 . . . 302	218/218 (100%)
	aa. [WO200037491-A2,
	29 JUN. 2000]
AAB28674	Human	1 . . . 218	218/218 (100%)	e−128
	carbohydrate-modifying	85 . . . 302	218/218 (100%)
	enzyme Incyte ID No:
	983984CD1 - Homo sapiens,
	302 aa. [WO200063351-A2,
	26 OCT. 2000]
AAB24495	Human secreted protein	1 . . . 218	217/218 (99%)	e−128
	sequence encoded by gene 5	128 . . . 345	217/218 (99%)
	SEQ ID NO: 120 - Homo
	sapiens, 345 aa.
	[WO200035937-A1,
	22 JUN. 2000]

[0578] In a BLAST search of public sequence datbases, the NOV44a protein was found to have homology to the proteins shown in the BLASTP data in Table 44D.

TABLE 44D
Public BLASTP Results for NOV44a
			Identities/
Protein			Similarities for
Accession		NOV44a Residues/	the Matched	Expect
Number	Protein/Organism/Length	Match Residues	Portion	Value
Q9H4F1	Alpha-N-acetyl-neuraminyl-2,3-beta-	1 . . . 218	218/218 (100%)	e−128
	galactosyl-1,3-N-acetylgalactosaminide	85 . . . 302	218/218 (100%)
	alpha-2,6-sialyltransferase (EC 2.4.99.7)
	(NeuAc-alpha-2,3-Gal-beta-1,3-GalNAc-
	alpha-2, 6-sialyltransferase) (ST6GalNAc
	IV) (Sialyltransferase 7D) - Homo sapiens
	(Human), 302 aa.
Q9H4F1	Alpha2,6-sialyltransferase - Homo sapiens	1 . . . 218	217/218 (99%)	e−128
	(Human), 302 aa.	85 . . . 302	218/218 (99%)
Q9NWU6	CDNA FLJ20593 fis, clone KAT08984 -	1 . . . 218	217/218 (99%)	e−127
	Homo sapiens (Human), 302 aa.	85 . . . 302	217/218 (99%)
Q9UKU1	NeuAc-alpha-2,3-Gal-beta-1,3-GalNAc-	1 . . . 218	216/218 (99%)	e−127
	alpha-2, 6-sialyltransferase	85 . . . 302	216/218 (99%)
	alpha2,6-sialyltransferase - Homo sapiens
	(Human), 302 aa.
Q9R2B6	Alpha-N-acetyl-neuraminyl-2,3-beta-	1 . . . 218	202/218 (92%)	e−118
	galactosyl-1,3-N-acetylgalactosaminide	143 . . . 360	207/218 (94%)
	alpha-2,6-sialyltransferase (EC 2.4.99.7)
	(NeuAc-alpha-2,3-Gal-beta-1,3-GalNAc-
	alpha-2, 6-sialyltransferase) (ST6GalNAc
	IV) (Sialyltransferase 7D) - Mus musculus
	(Mouse), 360 aa.

[0579] PFam analysis predicts that the NOV44a protein contains the domains shown in the Table 44E.

TABLE 44E
Domain Analysis of NOV44a
			Identities/
		NOV44a	Similarities
		Match	for the Matched	Expect
	Pfam Domain	Region	Region	Value
	Glyco_transf_29	1 . . . 202	65/324 (20%)	6e−43
			184/324 (57%)

Example 45

[0580] The NOV45 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 45A.

TABLE 45A
NOV45 Sequence Analysis
	SEQ ID NO: 185	1475 bp
NOV45a,	AGGACTCCAAGCGCCATGGCCGCTGCCCCCCGAGCCCGGGTCGCGTACTTGCTCAGGCAACTCCAAC
CG171841-01
DNA Sequence	GCGCAGCATGGCTGTTTCAAATATTAGATATGGAGCAGCAGTTACAAAGGAAGTAGGAATGGCAGAC
	CTAAAAAACATGGGTGCTAAAAATGTGTGCTTGATGACAGACAAGAACCTCTCCAAGCTCCCTCCTG
	TGCAAGTAGCTATGGATTCCCTAGTGAAGAATGGCATCCCCTTTACGGTTTATGATAATGTGAGAGT
	GGAACCAACGGATAGCTTCATGGAAGCTATTGAGTTTGCCCAAAAGGGAGCTTTTGATGCCTATGTT
	CCTGTCGGTGGTGGCTCTACCATGGACACCTGTAAGGCTGCTAATCTGTATGCATCCAGCCCTCATT
	CTGATTTCCTAGATTATGTCAGTGCCCCCATTGGCAAGGGAAAGCCTGTGTCTGTGCCTCTTAAGCC
	TCTGATTGCAGTGCCAACTACCTCAGGAACCGGGAGTGAAACTACTGGGGTTGCCATTTTTGACTAT
	GAACACTTGAAAGTAAAAATTGGCATCACTTCGAGAGCCATCAAACCCACACTGGGACTGATTGATC
	CTCTGCACACCCTCCACATGCCTGCCCGAGTGGTCGCCAACAGTGGCTTTCATGTGTTTAGCCATGC
	CCTGGAGTCATACACCACCCTGCCCTACCACCTGCGGAGCCCCTGCCCTTCAAATCCCATCACACGG
	CCTGCGTACCAGGGCAGCAACCCAATCAGTGACATTTGGGCTATCCACGCGCTGCGGATCGTGGCTA
	AGTATCTGAAGGCTGTCAGAAATCCCGATGATCTTGAAGCAAGGTCTCATATGCACTTGGCAAGTGC
	TTTTGCTGGCATCGGCTTTGGAAATGCTCCTGTTCATCTGCATGGAATGTCTTACCCAATTTCAGGT
	TTAGTGAAGATGTATAAAGCAAAGCATTACAATGTGGATCACCCACTGGTCCCCCATGGCCTTTCTG
	TGGTGCTCACGTCCCCAGCGGTGTTCACTTTCACCGCCCAGATGTTTCCAGAGCGACACCTGGAGAT
	GGCACAACTTCTAGGAGCCGACACCCGCACTGCCAGGATCCAAGATCCAGGGCTGGTGTTGGCAGAC
	ACGCTCCGGAAATTCTTATTCGATCTGGATGTTGATGATGGCCTAGCAGCTGTTGGTTACTCCAAAG
	CTGATATCCCCGCACTAGTGAAACGAACGCTGCCCCAGGAAAGGGTCACCAAGCTTGCACCCTGTCC
	CCAGTCAGAAGAGGATCTGGCTGCTCTGTTTGAAGCTTCAATGAAACTGTATTAATTGTCATTTTAA
	CTGAAAGAATTACCGCTGGCCATTGTAGTGCTGAGAGCAAGAGCTGATCTAGCTAGGGCTTTGTCTT
	TTCATCTTTGCGCATAACTTACCTGTTACCAGTATAGGTGGGATATACATTTATCTTCCAGCAAATT
	C
	ORF Start: ATG at 75		ORF Stop: TAA at 1326
	SEQ ID NO: 186	417 aa	MW at 44871.2 kD
NOV45a,	MAVSNIRYGAAVTKEVCMADLKNMGAKNVCLNTDKNLSKLPPVQVAMDSLVKNGIPFTVYDNVRVEP
CG171841-01
Protein Sequence	TDSFMEAIEFAQKGAFDAYVAVGGGSTMDTCKAANLYASSPHSDFLDYVSAPIGKGKPVSVPLKPLI
	AVPTTSGTGSETTGVAIFDYEHLKVKIGITSRAIKPTLGLIDPLHTLHMPARVVANSGFDVFSHALE
	SYTTLPYHLRSPCPSNPITRPAYQGSNPISDIWAIHALRIVAKYLKAVRNPDDLEARSHMHLASAFA
	GIGFGNAGVHLHGMSYPISGLVKMYKAKDYNVDHPLVPHGLSVVLTSPAVFTFTAQMFPERHLEMAE
	LLGADTRTARIQDAGLVLADTLRKFLFDLDVDDGLAAVGYSKADIPALVKGTLPQERVTKLAPCPQS
	EEDLAALFEASMXLY

[0581] Further analysis of the NOV45a protein yielded the following properties shown in Table 45B.

TABLE 45B
Protein Sequence Properties NOV45a
PSort analysis:   0.4500 probability located in cytoplasm; 0.3188
                  probability located in microbody (peroxisome);
                  0.2355 probability located in lysosome (lumen);
                  0.1000 probability located in mitochondrial
                  matrix space
SignalP analysis: No Known Signal Sequence Predicted

[0582] A search of the NOV45a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 45C.

TABLE 45C
Geneseq Results for NOV45a
			Identities/
			Similarities for
Geneseq	Protein/Organism/Length	NOV45a Residues/	the Matched	Expect
Identifier	[Patent #, Date]	Match Residues	Region	Value
AAE21522	Human dehydrogenase	1 . . . 417	413/420 (98%)	0.0
	DHDR-6 protein - Homo	49 . . . 467	414/420 (98%)
	sapiens, 467 aa.
	[WO200216562-A2,
	28 FEB. 2002]
AAB73686	Human oxidoreductase	1 . . . 417	412/420 (98%)	0.0
	protein ORP-19 - Homo	49 . . . 467	413/420 (98%)
	sapiens, 467 aa.
	[WO200144448-A2,
	21 JUN. 2001]
ABB59876	Drosophila melanogaster	1 . . . 417	254/420 (60%)	e−146
	polypeptide SEQ ID NO	46 . . . 464	327/420 (77%)
	6420 - Drosophila
	melanogaster, 464 aa.
	[WO200171042-A2,
	27 SEP. 2001]
ABG08093	Novel human diagnostic	62 . . . 322	240/268 (89%)	e−131
	protein #8084 - Homo	1 . . . 268	243/268 (90%)
	sapiens, 268 aa.
	[WO200175067-A2,
	11 OCT. 2001]
AAB42855	Human ORFX ORF2619	247 . . . 417	168/172 (97%)	7e−91
	polypeptide sequence SEQ	41 . . . 212	170/172 (98%)
	ID NO: 5238 - Homo sapiens,
	212 aa. [WO200058473-A2,
	05 OCT. 2000]

[0583] In a BLAST search of public sequence datbases, the NOV45a protein was found to have homology to the proteins shown in the BLASTP data in Table 45D.

TABLE 45D
Public BLASTP Results for NOV45a
			Identities/
Protein			Similarities for
Accession		NOV45a Residues/	the Matched	Expect
Number	Protein/Organism/Length	Match Residues	Portion	Value
CAD28993	Sequence 4 from Patent	1 . . . 417	413/420 (98%)	0.0
	WO0216562 - Homo sapiens	49 . . . 467	414/420 (98%)
	(Human), 467 aa.
Q96MF9	CDNA FLJ32430 fis, clone	1 . . . 417	412/420 (98%)	0.0
	SKMUS2001129, weakly	1 . . . 419	413/420 (98%)
	similar to NAD-dependent
	methanol dehydrogenase (EC
	1.1.1.244) - Homo sapiens
	(Human), 419 aa.
Q8RON6	Hypothetical 45.0 kDa	1 . . . 417	372/420 (88%)	0.0
	protein - Mus musculus	1 . . . 419	394/420 (93%)
	(Mouse), 419 aa.
Q9W265	T3DH protein - Drosophila	1 . . . 417	254/420 (60%)	e−145
	melanogaster (Fruit fly), 464	46 . . . 464	327/420 (77%)
	aa.
Q95S86	GM05887p - Drosophila	1 . . . 417	254/420 (60%)	e−145
	melanogaster (Fruit fly), 425	7 . . . 425	327/420 (77%)
	aa.

[0584] PFam analysis predicts that the NOV45a protein contains the domains shown in the Table 45E.

TABLE 45E
Domain Analysis of NOV45a
	Pfam Domain	NOV45a	Identities/	Expect
		Match	Similarities	Value
		Region	for the
			Matched Region
	Fe-ADH	4 . . . 205	68/216 (31%)	5.6e−28
			143/216 (66%)
	Fe-ADH	228 . . . 288	30/68 (44%)	2.5e−10
			51/68 (75%)

Example 46

[0585] The NOV46 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 46A.

TABLE 46A
NOV46 Sequence Analysis
	SEQ ID NO: 187	1310 bp
NOV46a,	CTACTCTCAGCCAGGAATCATGTCTTGGGCCGCTCGCCCGCCCTTCCTCCCTCAGCGGCATGCCGCA
CG173017-01
DNA Sequence	GGGCAGTGTGGGCCGGTGGGGGTGCGAAAAGAAATGCATTGTGGGGTCGCGTCCCGGTGGCGGCGGC
	GACGGCCCTGGCTGGATCCCGCAGCGGCGGCGGCGGCGGCGGTGGCAGGCGGAGAACAACAACCCC
	GGAGCCGGAGCCAGGGGAGGCTGGACGCGACGGGATGGGCGACAGCGGGCGGGTGGCCCTGGGGCT
	GGCAAACGCCTATGTGCAATCTGCGGGGACAGAAGCTCACGCAAACACTACGGGGTTTACAGCTGTG
	AGGGTTGCAAGGGCTTCTTCAAACGCACCATCCGCAAAGACCTTACATACTCTTGCCGGGACAACAA
	AGACTGCACAGTGGACAAGCGCCAGCGGAACCGCTGTCAGTACTGCCGCTATCAGAAGTGCCTGGCC
	ACTGGCATGAAGAGGGAGGCGGTACAGGAGGAGCGTCAGCGGGGAAAGGACAGGGATGGGGATGGGG
	AGGGGGCTGGGGGAGCCCCCGAGGAGATGCCTGTGGACAGGATCCTGGAGGCAGAGCTTGCTGTGGA
	ACAGAAGAGTGACCAGGGCGTTGAGGGTCCTGGGGGAACCGGGGGTAGCGGCAGCAGCCCAAATGAC
	CCTGTGACTAACATCTGTCAGGCAGCTGACAAACAGCTATTCACGCTTGTTGAGTGGGCGAAGAGGA
	TCCCACACTTTTCCTCCTTGCCTCTGGATGATCAGGTCATATTGCTGCGGGCAGGCTGGAATGAACT
	CCTCATTGCCTCCTTTTCACACCGATCCATTGATGTTCGAGATGGCATCCTCCTTGCCACAGGTCTT
	CACGTGCACCGCAACTCAGCCCATTCAGCAGGAGTAGGAGCCATCTTTGATCGGGTGCTGACAGAGC
	TAGTGTCCAAAATCCGTGACATGAGGATGGACAAGACAGAGCTTGGCTGCCTGAGGGCAATCATTCT
	GTTTAATCCAGATGCCAAGGGCCTCTCCAACCCTAGTGAAGGTGGAGGTCCTGCGGGAGAAGTGTAT
	GCATCACTGGAGACCTACTGCAAACAGAAGTACCCTGAGCAGCAGGGACGGTTTCCCAAGCTGCTGC
	TACGTCTTCCTGCCCTCCGGTCCATTCGCCTTAAGTGTCTAGAGCATCTGTTTTTCTTCAAGCTCAT
	TGGTGACACCCCCATCGACACCTTCCTCATGGAGATGCTTGAGGCTCCCCATCAACTGGCCTGAGCT
	CAGACCCAGACGTGGTGCTTCTCCACACTGGAGGAGC
	ORF Start: ATG at 20		ORF stop: TGA at 1268
	SEQ ID NO: 188	416 aa	MW at 45778.7 kD
NOV46a,	MSWAARPPFLPQRHAAGQCGPVGVRKEMHCGVASRWRRRRPWLDPAAAAAAAVACGEQQTPEPEPGE
CG173017-01
Protein Sequence	AGRDGMGDSGRGGPGAGKRLCAICGDRSSGKHYGVYSCEGCKGFFKRTIRKDLTYSCRDNKDCTVDK
	RQRNRCQYCRYQKCLATGMKREAVQEERQRGKDRDGDGEGAGGAPEEMPVDRILEAELAVEQKSDQG
	VEGPGGTGGSGSSPNDPVTNTCQAADKQLFTLVEWAKRIPHFSSLPLDDQVILLRAGWNELLIASFS
	HRSIDVRDGILLATGLHHRNSAflSAGVGAIFDRVLTELVSKMRDMRMDKTELGCLRAITLFNPDAK
	GLSNPSEVEVLREKVYASLETYCKQKYPEQQGRFAXLLLRLPALRSIGLKCLEHLFFFKLIGDTPID
	TFLMEMLEAPHQLA

[0586] Further analysis of the NOV46a protein yielded the following properties shown in Table 46B.

TABLE 46B
Protein Sequence Properties NOV46a
PSort analysis:   0.9700 probability located in nucleus; 0.3000
                  probability located in microbody (peroxisome);
                  0.1000 probability located in mitochondrial matrix
                  space; 0.1000 probability located in lysosome (lumen)
SignalP analysis: No Known Signal Sequence Predicted

[0587] A search of the NOV46a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 46C.

TABLE 46C
Geneseq Results for NOV46a
			Identities/
			Similarities for
Geneseq	Protein/Organism/Length	NOV46a Residues/	the Matched	Expect
Identifier	[Patent #, Date]	Match Residues	Region	Value
AAU78297	Human Retinoid X Receptor	41 . . . 416	346/378 (91%)	0.0
	beta (RXRbeta) protein -	156 . . . 533	352/378 (92%)
	Homo sapiens, 533 aa.
	[WO200218420-A2,
	07 MAR. 2002]
AAR72483	Human H-2RIIBP - Homo	41 . . . 416	346/378 (91%)	0.0
	sapiens, 533 aa.	156 . . . 533	352/378 (92%)
	[US5403925-A,
	04 APR. 1995]
AAR39468	hRXR-beta1 - Homo sapiens,	41 . . . 416	346/378 (91%)	0.0
	533 aa. [WO9315216-A,	156 . . . 533	352/378 (92%)
	05 AUG. 1993]
AAR39469	hRXR-beta2 - Homo sapiens,	41 . . . 416	345/378 (91%)	0.0
	510aa. [WO9315216-A,	133 . . . 510	351/378 (92%)
	05 AUG. 1993]
AAY21625	Ligand binding domain of	41 . . . 416	345/378 (91%)	0.0
	nuclear receptor hRXRbeta -	148 . . . 525	351/378 (92%)
	Homo sapiens, 525 aa.
	[W09926966-A2,
	03 JUN. 1999]

[0588] In a BLAST search of public sequence datbases, the NOV46a protein was found to have homology to the proteins shown in the BLASTP data in Table 46D.

TABLE 46D
Public BLASTP Results for NOV46a
			Identities/
Protein			Similarities for
Accession		NOV46a Residues/	the Matched	Expect
Number	Protein/Organism/Length	Match Residues	Portion	Value
S37781	retinoid X receptor beta -	41 . . . 416	346/378 (91%)	0.0
	human, 533 aa.	156 . . . 533	352/378 (92%)
Q95L53	Retinoid X receptor beta -	41 . . . 416	346/378 (91%)	0.0
	Mustela vison (American	148 . . . 525	352/378 (92%)
	mink), 525 aa (fragment).
P28702	Retinoic acid receptor	41 . . . 416	346/378 (91%)	0.0
	RXR-beta - Homo sapiens	156 . . . 533	352/378 (92%)
	(Human), 533 aa.
A41651	retinoic acid receptor	41 . . . 416	341/378 (90%)	0.0
	coregulator - rat, 451 aa.	74 . . . 451	349/378 (92%)
D41727	retinoid X receptor beta -	41 . . . 416	341/378 (90%)	0.0
	mouse, 448 aa.	71 . . . 448	349/378 (92%)

[0589] PFam analysis predicts that the NOV46a protein contains the domains shown in the Table 46E.

TABLE 46E
Domain Analysis of NOV46a
		Identities/
		Similarities
		for the Matched	Expect
Pfam Domain	NOV46a Match Region	Region	Value
zf-C4	86 . . . 161	49/77 (64%)	1.5e−54
		73/77 (95%)
hormone_rec	227 . . . 409	74/207 (36%)	3.3e−68
		157/207 (76%)

Example 47

[0590] The NOV47 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 47A.

TABLE 47A
NOV47 Sequence Analysis
	SEQ ID NO: 189	1229 bp
	NOV47a, CCGAGACCATGGGGAACCTCGTGGCGCTGGTCCTGCTGGGGGTCGGCCTGTCCTTAGTCGGAGAT
	CG173347-01
	DNA Sequence	GTTTCTGGCGTTTAGAGAAAGGGTGAATGCCTCTCGAGAAGTCGAGCCAGTAGAACCTGAAAACTGC
		CACCTTATTGAGCAACTTGAAAGTGGCTCTGAAGATATTGATATACTTCCTAGTGGGCTGGCTTTTA
		TCTCCAGTCTGCAGGTCTGTTGGAGTTTGCTGGAAGTCCACTCCAGACCCTGTTTGCCTCGGTATCA
		CCAGTGGAGGCTGCAGAACGGCAAATATTGCTGCCTGATTTTTCTTCTGGAAGCTTCATCCCAGAGG
		GGCATCCGCCTGTATGAGGGATTAAAATATCCACGCATGCCAAACTTTGCGCCAGATGAACCAGGAA
		AAATCTTCTTGATGGATCTGAATGAACAAAACCCAAGGGCACAAGCACTACAAATCAGTGGTGGATT
		TGACAAAGAATTATTTAATCCACATGGGATCAGTATTTTCATCGACAAAGACAATACTGTGTATCTT
		TATGTTGTGAATCATCCCCACATGAAGTCCACTGTGGAGATATTTAAATTTGAGGAACAACAACGTT
		CTCTGGTATACCTGAAAACTATAAAACATGAACTTCTCAAAAGTGTGAATGACATTGTGGTTCTTGG
		ACCAGAACAGTTCTATGCCACCAGAGACCACTATTTTACCAACTCCCTCCTGTCATTTTTTGAGATG
		ATCTTGGATCTTCGCTGGACTTATGTTCTTTTCTACAGCCCAAGGGAGGTTAAAGTGGTGGCCAAAG
		GATTTTGTAGTGCCAATGGGATCACAGTCTCAGCAGACCAGAAGTATGTCTATGTAGCTGATGTAGC
		AGCTAAGAACATTCACATAATGGAAAACATGATAACTGGGATTTAACTCAACTGAAAGGTGATACAG
		TTGGGCACCTTAGTGGATAACCTGACTGTCGATCCTGCCACACGAGACATTTTGGCAGGATGCCATC
		CTAATCCTATGAAGCTACTGAACTATAACCCTGAGGACCCTCCAGGATCAGAAGTACTTCGCATCCA
		GAATGTTTTGTCTGAGAAGCCCAGGGTGAGCACCGTGTATGCCAACAATGGCTCTGTGCTTCAAGGC
		ACCTCTGTGGCTTCTGTGTACCATGGGAAAATTCTCATACGCACCGTATTTCNCAAAACTCTGTACT
		GTGAGCTCTAGACTCTAGATAGT
	ORF Start: ATG at 9		ORF Stop: TAG at 1215
	SEQ ID NO: 190	402 aa	MW at 45160.5 kD
	NOV47a, MGKLVALVLLGVGLSLVGEMFLAFRERVNASREVEPVEPENCHLIEELESGSEDIDILPSGLAFISS
	CG173347-01
	Protein Sequence	LQVCWSLLEVHSRPCLPGYHQWRLQNGKYCCLIFLLEASSQRGIRLYEGLKYPGMPNFAPDEPGKIF
	LMDLNEQNPRAQALEISGGFDKELFNPHGISIFIDKDNTVYLYVVNHPHMKSTVEIFKFEEQQRSLV
	YLKTIKHELLKSVNDTVVLGPEQFYATRDHYFTNSLLSFFEMILDLRWTYVLFYSPREVKVVAKGFC
	SANGITVSADQKYVYVADVAAKNIHIMEKHDNWDLTQLKVIQLGTLVDNLTVDPATGDILAGCHPNP
		MXLLNYNPEDPPGSEVLRIQNVLSEKPRVSTVYANNGSVLQGTSVASVYHGKTLIGTVFXKTLYCEL

[0591] Further analysis of the NOV47a protein yielded the following properties shown in Table 47B.

TABLE 47B
Protein Sequence Properties NOV47a
PSort analysis:   0.8200 probability located in outside;
                  0.1900 probability located in lysosome (lumen);
                  0.1000 probability located in endoplasmic
                  reticulum (membrane);
                  0.1000 probability located in endoplasmic
                  reticulum (lumen)
SignalP analysis: Cleavage site between residues 31 and 32

[0592] A search of the NOV47a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 47C.

TABLE 47C
Geneseq Results for NOV47a
		NOV47a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
ABB97287	Novel human protein SEQ ID	1 . . . 402	352/402 (87%)	0.0
	NO: 555 - Homo sapiens, 354	1 . . . 354	352/402 (87%)
	aa. [WO200222660-A2,
	21-MAR-2002]
AAG75494	Human colon cancer antigen	2 . . . 402	352/401 (87%)	0.0
	protein SEQ ID NO: 6258 -	18 . . . 370	352/401 (87%)
	Homo sapiens, 370 aa.
	[WO200122920-A2,
	05-APR-2001]
ABG08350	Novel human diagnostic	1 . . . 402	330/407 (81%)	e−178
	protein #8341 - Homo	24 . . . 382	333/407 (81%)
	sapiens, 382 aa.
	[WO200175067-A2,
	11-OCT-2001]
AAU11925	Protein sequence of rabbit	1 . . . 402	294/403 (72%)	e−164
	paraoxonase-3 (PON3)	1 . . . 355	318/403 (77%)
	mutant D324N - Oryctolagus
	cuniculus, 355 aa.
	[WO200190336-A2,
	29-NOV-2001]
AAU11922	Protein sequence of rabbit	1 . . . 402	294/403 (72%)	e−164
	paraoxonase-3 (PON3)	1 . . . 355	318/403 (77%)
	mutant N169D - Oryctolagus
	cuniculus, 355 aa.
	[WO200190336-A2,
	29-NOV-2001]

[0593] In a BLAST search of public sequence datbases, the NOV47a protein was found to have homology to the proteins shown in the BLASTP data in Table 47D.

TABLE 47D
Public BLASTP Results for NOV47a
		NOV47a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q15166	Serum	1 . . . 402	354/402 (88%)	0.0
	paraoxonase/arylesterase 3	1 . . . 354	354/402 (88%)
	(EC 3.1.1.2) (EC 3.1.8.1)
	(PON 3) (Serum
	aryldiakylphosphatase 3)
	(A-esterase 3) (Aromatic
	esterase 3) - Homo sapiens
	(Human), 354 aa.
Q9BZH9	Paraoxanase-3 - Homo	1 . . . 402	351/402 (87%)	0.0
	sapiens (Human), 354 aa	1 . . . 354	351/402 (87%)
	(fragment).
Q9BGN0	Paraoxonase 3 - Oryctolagus	1 . . . 402	293/402 (72%)	e−164
	cuniculus (Rabbit), 354 aa.	1 . . . 354	318/402 (78%)
Q62087	Serum	1 . . . 402	283/402 (70%)	e−158
	paraoxonase/arylesterase 3	1 . . . 354	314/402 (77%)
	(EC 3.1.1.2) (EC 3.1.8.1)
	(PON 3) (Serum
	aryldiakylphosphatase 3)
	(A-esterase 3) (Aromatic
	esterase 3) - Mus musculus
	(Mouse), 354 aa.
Q90952	Serum	1 . . . 402	230/402 (57%)	e−131
	paraoxonase/arylesterase 2	1 . . . 354	287/402 (71%)
	(EC 3.1.1.2) (BC 3.1.8.1)
	(PON 2) (Serum
	aryldiakylphosphatase 2)
	(A-esterase 2) (Aromatic
	esterase 2) - Gallus gallus
	(Chicken), 354 aa.

[0594] PFam analysis predicts that the NOV47a protein contains the domains shown in the Table 47E.

TABLE 47E
Domain Analysis of NOV47a
	NOV47a	Identities/
	Match	Similarities
Pfam Domain	Region	for the Matched Region	Expect Value
Arylesterase	2 . . . 402	230/422 (55%)	1.2e−190
		348/422 (82%)

Example 48

[0595] The NOV48 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 48A.

TABLE 48A
NOV48 Sequence Analysis
	SEQ ID NO: 191	2109 bp
NOV48a,	CTTCCATACCTCCCCGGCTCCGCTCGGTTCCTGGCCACCCCGCAAGCCCCTGCCCAGGTGCCATGGC
CG56234-01
DNA Sequence	CGCATTGTACCGCCCTGGCCTGCGGCTTAACTGGCATGGGCTGAGCCCCTTGGGCTGGCCATCATGC
	CGTAGCATCCAGACCCTGCGAGTGCTTAGTGCAGATCTGGGCCAGCTTCCCACTGGCATTCGAGATT
	TTGTAGAGCACAGTGCCCGCCTGTGCCAACCAGAGGGCATCCACATCTGTGATGGAACTGAGCCTGA
	GAATACTGCCACACTGACCCTGCTGGAGCAGCAGGCCCTCATCCGAAAGCTCCCCAAGTACAATAAC
	TGCTGGCTGGCCCGCACAGACCCCAAGGATGTGGCACGAGTAGAGAGCAAGACGGTGATTGTAACTC
	CTTCTCAGCGGGACACGGTACCACTCCCGCCTGGTGGCGCCCGTGGGCAGCTGGGCAACTGGATGTC
	CCCAGCTGATTTCCAGCGAGCTGTGGATGAGAGGTTTCCAGGCTGCATGCAGGGCCGCACCATGTAT
	GTGCTTCCATTCAGCATGGGTCCTGTGGGCTCCCCGCTGTCCCGCATCGGGGTGCAGCTCACTGACT
	CAGCCTATGTGGTGGCAAGCATGCGTATTATGACCCGACTGGGGACACCTGTGCTTCAGGCCCTGGC
	AGATGGTGACTTTGTCAAGTGTCTGCACTCCGTGGGCCAGCCCCTGACAGGACAAGGGGAGCCAGTG
	AGCCAGTGGCCGTGCAACCCAGAGAAAACCCTGATTGGCCACGTGCCCGACCAGCGGGAGATCATCT
	CCTTCGGCAGCGGCTATGGTGGCAACTCCCTCCTGGGCAAGAAGTGCTTTGCCCTACGCATCGCCTC
	TCGGCTGGCCCGGGATGAGGGCTGGCTGGCAGAGCACATGCTGATCCTGGGCATCACCAGCCCTGCA
	GGGAAGAAGCGCTATGTGGCAGCCGCCTTCCCTAGTGCCTGTGGCAAGACCAACCTGGCTATGATGC
	GGCCTGCACTGCCAGGCTGGAAAGTGGAGTGTGTGGGGGATCATATTGCTTGCATGAGGTTTGACAG
	TGAAGGTCGACTCCCGGCCATCAACCCTGAGAACGGCTTCTTTGGGGTTGCCCCTGGTACCTCTGCC
	ACCACCAATCCCAACGCCATGGCTACAATCCAGAGTAACACTATTTTTACCAATGTGGCTGAGACCA
	GTGATCGTGGCCTGTACTGGGAGGGCATTGACCAGCCTCTTCCACCTGGTGTTACTGTGACCTCCTG
	GCTCGGCAAACCCTGGAAATCTGGTGACAAGGAGCCCTGTGCACATCCCAACTCTCGATTTTGTGCC
	CCGGCTCGCCAGTGCCCCATCATGGACCCAGCCTGGGAGGCCCCAGAGGGTGTCCCCATTGACGCCA
	TCATCTTTGGTGGCCGCAGACCCAAAGGGGTACCCCTGGTATACGACGCCTTCAACTCGCGTCATGG
	GGTGTTTGTGGGCAGCGCCATGCGCTCTGAGTCCACTGCTGCAGCAGAACACAAAGGGAAGATCATC
	ATGCACGACCCATTTGCCATGCGGCCCTTTTTTGGCTACAACTTCGGGCACTACCTGAAACACTGGC
	TGAGCATGGAAGGGCGCAACGGGGCCCAGCTGCCCCGTATCTTCCATGTCAACTGGTTCCGGCGTGA
	CGAGGCAGGGCACTTCCTGTGGCCAGGCTTTGGGGAGAATGCTCGGGTGCTAGACTGGATCTGCCGG
	CGGTTAGAGGGGGAGGACAGTGCCCGAGAGACACCCATTGGGCTGGTACCAAAGGAAGGAGCCTTGG
	ATCTCAGCGGCCTCAGAGCTATAGACACCACTCAGCTGTTCTCCCTCCCCAAGGACTTCTGGGAACA
	GGAGGTTCGTGACATTCGGAGCTACCTGACAGAGCAGGTCAACCAGGATCTGCCCAAAGAGGTGTTC
	GCTGAGCTTGAGGCCCTGGAGAGACGTCTGCACAAAATGTGACCTCAGGCCCTAGTCTAGCAAGAGG
	ACATAGCACCCTCATCTGGGAATAGGGAAGGCACCTTGCAGAAAATATGAGCAATTTGATATTAACT
	AACATCTTCAATGTGCCATAGACCTTCCCACA
	ORF Start: ATG at 63		ORF Stop: TGA at 1983
	SEQ ID NO: 192	640 aa	MW at 70688.2 kD
NOV48a,	MAALYRPGLRLNWHGLSPLGWFSCRSIQTLRVLSGDLGQLPTGIRDFVEHSARLCQPEGIHICDGTE
CG56234-01
Protein Sequence	AENTATLTLLEQQGLIRKLPKYNNCWLARTDFKDVARVESKTVIVTPSQRDTVPLPPGGARGQLGNW
	MSPADFQRAVDERFPGCMQGRTMYVLPFSMGPVGSPLSRIGVQLTDSAYVVASMRIMTRLGTPVLQA
	LGDGDFVKCLHSVGQPLTGQGEPVSQWPCNPEKTLIGHVPDQREIISFGSGYGGNSLLGKKCFALRI
	ASRLARDEGWLAEHMLILGITSPAGKKRYVAAAFPSACGKTNLAMMRPALPGWKVECVGDDIAWMRF
	DSECRLRAINPENGFFGVAPGTSATTNPNAMATIQSNTTFTNVAETSDGGVYWEGIDQPLPPGVTVT
	SWLGKPWKSGDKEPCAHPNSRFCAPARQCPIMDPAWEAPEGVPIDAIIFGGRRPKGVPLVYEAFNWR
	HGVFVGSAMRSESTAAAEHKGKIIMHDPFAMRPFFGYNFGHYLEHWLSMEGRKGAQLPRIFHVNWFR
	RDEAGHFLWPGFGENARVLDWICRRLEGEDSARETPIGLVPKEGALDLSGLRAIDTTQLFSLPKDFW
	EQEVRDIRSYLTEQVNQDLPKEVLAELEALERRVHKM
	SEQ ID NO: 193	2069 bp
NOV48b,	CCCGCCTTCCATACCTCCCCGGCTCCGCTCCGTTCCTGGCCACCCCGCAGCCCCTGCCCAGGTCCCA
CG56234-02
DNA Sequence	TGGCCGCATTGTACCGCCCTGGCCTGCGGCTTAACTGGCATGGGCTGAGCCCCTTGGGCTGGCCATC
	ATGCCGTAGCATCCAGACCCTGCGAGTGCTTAGTGGAGATCTGGGCCAGCTTCCCACTGGCATTCGA
	GATTTTGTAGACCACAGTGCCCGCCTGTGCCAACCAGAGAACATCCACATCTGTGATGGAACTGAGG
	CTGAGAATACTGCCACACTGACCCTGCTCGAGCAGCAGGGCCTCATCCGAAAGCTCCCCAAGTACAA
	TAACTGCTGGCTGGCCCGCACAGACCCCAAGGATGTCGCACGAGTAGAGAGCAAGACGGTGATTGTA
	ACTCCTTCTCAGCGGGACACGGTACCACTCCCGCCTGGTGGGGCCTGTGGGCAGCTGGGCAACTGGA
	TGTCCCCAGCTGATTTCCAGCGAGCTGTGGATCAGAGGTTTCCAGGCTGCATGCAGGGCCGCACCAT
	GTATGTGCTTCCATTCAGCATGGGTCCTGTCGGCTCCCCGCTGTCCCGCATCGGGGTGCAGCTCACT
	GACTCAGCCTATGTGGTGCCAACCATGCGTATTATAACCCGACTGGCCACACCTGTGCTTCAGGCCC
	TGGGAGATCGTGACTTTGTCAAGTGTCTGCACTCCGTGGGCCAGCCCCTGACAGGACAAGGGGAGCC
	AGTGAGCCAGTGGCCGTGCAACCCAGAGAAAACCCTGATTGGCCACGTGCCCGACCAGCGGGAGATC
	ATCTCCTTCGGCAGCGGCTATGGTGGCAACTCCCTGCTGGGCAAGAAGTGCTTTGCCCTACGCATCG
	CCTCTCGGCTGGCCCGGGATGAGGGCTCGCTGGCAGAGCACATGCTGATCCTGGGCATCACCAGCCC
	TGCAGGGAAGAAGGCGCTATGTGCAGCCGCCTTCCCTAGTGCCTGTGGCAAGACCAACCTGGCTATG
	ATGCGGCCTGCACTGCCAGGCTGGAAAGTGGAGTGTGTCGGGGATGATATTGCTTGGATGAGGTTTG
	ACAGTGAAGGTCGACTCCGGGCCATCAACCCTGAGAACGGCTTCTTTGGGGTTGCCCCTGGTACCTC
	TGCCACCACCAATCCCAACGCCATGGCTACAATCCAGAGTAACACTATTTTTACCAATGTGGCTGAG
	ACCAGTCATGGTGGCGTGTACTGGGAGGGCATTGACCAGCCTCTTCCACCTGGTGTTACTGTGACCT
	CCTGGCTGGGCAAACCCTGGAAACCTGGTGACAAGGAGCCCTGTGCACATCCCAACTCTCGATTTTG
	TGCCCCGGCTCCCCAGTGCCCCATCATGGACCCAGCCTGGGAGGCCCCAGAGGGTGTCCCCATTGAC
	GCCATCATCTTTGGTGGCCGCAGACCCAAAGGGAAGATCATCATGCACGACCCATTTGCCATGCGGC
	CCTTTTTTGGCTACAACTTCGGGCACTACCTGGAACACTGGCTGAGCATGGAAGGGCGCAAGGGGGC
	CCAGCTGCCCCGTATCTTCCATGTCAACTGGTTCCGGCGTGACGAGGCAGGGCACTTCCTGTGGCCA
	GGCTTTGGGGAGAATGCTCGCGTGCTAGACTGGATCTGCCGGCGGTTAGAGAAGGAGGACAGTGCCC
	GAGAGACACCCATTGGGCTGGTGCCAAAGGAAGGAGCCTTGGATCTCAGCGGCCTCAGAGCTATAGA
	CACCACTCAGCTGTTCTCCCTCCCCAAGGACTTCTGGGAACAGGAGGTTCGTGACATTCGGAGCTAC
	CTGACAGACCAGGTCAACCAGGATCTGCCCAAAGAGGTGTTGGCTGAGCTTGAGGCCCTGGAGAGAC
	GTGTGCACAAAATGTGACCTGAGGCCTAGTCTAGCAAGAGGACATAGCACCCTCATCTGGGAATAGG
	GAAGGCACCTTGCAGAAAATATGAGCAATTGATATTAACTAACATCTTCAATGTGCCATAGACCTTC
	CCACAAAGACTGTCCAATAATAAGAGATGCTTATCTATTTTAAAAAAAAAAAAAAAAAA
	ORF Start: ATG at 67		ORF Stop: TGA at 1891
	SEQ ID NO: 194	608 aa	MW at 67027.1 kD
NOV48b,	MAALYRPGLRLNWHGLSPLGWPSCRSIQTLRVLSGDLGQLPTGIRDFVEHSARLCQPEGIHICDGTE
CG56234-02
Protein Sequence	AENTATLTLLEQQGLIRKLPKYNNCWLARTDPKDVARVESKTVIVTPSQRDTVPLPPGGACGQLGNW
	MSPADFQRAVDERFPGCMQGRTMYVLPFSMGPVGSPLSRIGVQLTDSAYVVASMRIMTRLGTPVLQA
	LGDGDFVKCLHSVGQPLTGQGEPVSQWPCNPEKTLTGHVPDQREIISFGSGYGGNSLLGKKCFALRI
	ASRLARDEGWLAEHMLILGITSPAGKKALCAAAFPSACGKTNLAMMRPALPGWKVECVGDDIAWMRE
	DSEGRLRAINPENGFFGVAPGTSATTNPNAMATIQSNTIFTNVAETSDGGVYWEGIDQPLPPGVTVT
	SWLGKPWKPGDKEPCAHPNSRFCAPARQCPIMDPAWEAPEGVPIDAIIFGGRRPKGKIIMHDPEAMR
	PFFGYNFGHYLEHWLSMEGRKGAQLPRIFHVNWFRRDEAGHFLWPGFGENARVLDWICRRLEGEDSA
	RETPIGLVPKECALDLSGLRAIDTTQLFSLPKDFWEQEVRDIRSYLTEQVNQDLPKEVLAELEALER
	RVHKM

[0596] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 48B.

TABLE 48B
Comparison of NOV48a against NOV48b.
Protein	NOV48a Residues/	Identities/
Sequence	Match Residues	Similarities for the Matched Region
NOV48b	1 . . . 640	577/640 (90%)
	1 . . . 608	577/640 (90%)

[0597] Further analysis of the NOV48a protein yielded the following properties shown in Table 48C.

TABLE 48C
Protein Sequence Properties NOV48a
PSort analysis:   0.6402 probability located in microbody (peroxisome);
                  0.3000 probability located in nucleus; 0.2412
                  probability located in lysosome (lumen); 0.1000
                  probability located in mitochondrial matrix space
SignalP analysis: No Known Signal Sequence Predicted

[0598] A search of the NOV48a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 48D.

TABLE 48D
Geneseq Results for NOV48a
		NOV48a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAY80296	Human mitochondrial	1 . . . 640	634/640 (99%)	0.0
	phosphoenolpyruvate	1 . . . 640	634/640 (99%)
	carboxykinase SEQ ID NO: 1 -
	Homo sapiens, 640 aa.
	[US6030837-A,
	29-FEB-2000]
AAB71890	Mouse PEPCK-cytosolic	31 . . . 640	440/610 (72%)	0.0
	protein - Mus musculus, 622	14 . . . 622	519/610 (84%)
	aa. [US6187545-B1,
	13-FEB-2001]
AAB71880	Human PEPCK-cytosolic	31 . . . 640	438/610 (71%)	0.0
	protein - Homo sapiens, 622	14 . . . 622	517/610 (83%)
	aa. [US6187545-B1,
	13-FEB-2001]
ABB65318	Drosophila melanogaster	27 . . . 640	394/616 (63%)	0.0
	polypeptide SEQ ID NO:	35 . . . 647	480/616 (76%)
	22746 - Drosophila
	melanogaster, 647 aa.
	[WO200171042-A2,
	27-SEP-2001]
ABB65322	Drosophila melanogaster	30 . . . 640	402/613 (65%)	0.0
	polypeptide SEQ ID NO:	29 . . . 638	469/613 (75%)
	22758 - Drosophila
	melanogaster, 638 aa.
	[WO200171042-A2,
	27-SEP-2001]

[0599] In a BLAST search of public sequence datbases, the NOV48a protein was found to have homology to the proteins shown in the BLASTP data in Table 48E.

TABLE 48E
Public BLASTP Results for NOV48a
		NOV48a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q16822	Phosphoenolpyruvate	1 . . . 640	635/640 (99%)	0.0
	carboxykinase, mitochondrial	1 . . . 640	635/640 (99%)
	precursor [GTP] (EC 4.1.1.32)
	(Phosphoenolpyruvate
	carboxylase) (PEPCK-M) -
	Homo sapiens (Human), 640 aa.
S69546	phosphoenolpyruvate	1 . . . 640	634/640 (99%)	0.0
	carboxykinase (GTP) (EC	1 . . . 640	634/640 (99%)
	4.1.1.32) precursor,
	mitochondrial - human, 640
	aa.
Q91Z10	Similar to	1 . . . 640	590/640 (92%)	0.0
	phosphoenolpyruvate	1 . . . 640	609/640 (94%)
	carboxykinase 2
	(mitochondrial) - Mus
	musculus (Mouse), 640 aa.
Q8R3X7	Similar to RIKEN cDNA	106 . . . 640	504/535 (94%)	0.0
	9130022B02 gene - Mus	1 . . . 535	518/535 (96%)
	musculus (Mouse), 535 aa (fragment).
P07379	Phosphoenolpyruvate	31 . . . 640	441/610 (72%)	0.0
	carboxykinase, cytosolic	14 . . . 622	520/610 (84%)
	[GTP] (EC 4.1.1.32)
	(Phosphoenolpyruvate
	carboxylase) (PEPCK-C) -
	Rattus norvegicus (Rat), 622
	aa.

[0600] PFam analysis predicts that the NOV48a protein contains the domains shown in the Table 48F.

TABLE 48F
Domain Analysis of NOV48a
		Identities/
Pfam		Similarities	Expect
Domain	NOV48a Match Region	for the Matched Region	Value
PEPCK	46 . . . 640	445/608 (73%)	0
		591/608 (97%)

Example 49

[0601] The NOV49 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 49A.

TABLE 49A
NOV49 Sequence Analysis
	SEQ ID NO: 195	1202 bp
NOV49a,	TGTAAGCGATCTGGTTCCCACCTCAGCCTCCCGAGTAGTGTCTTCAGGCCTATGGAGAGCAGCTTGC
CG56836-01
DNA Sequence	GTCGGCTGGGCCTGCAGTACCTGGTTTGCATAGATGATTCGCAGCTGGATCTAGGATCCGGCTTCCA
	ACATGTGGCAGCTCTCGGCCTCCCTCTGCTGCCTGCTGGTGTTGGCCAATGCCCGGAGCAGGCCCT
	TTTCCATCCCCTGTCGGATGAGCTGGTCAACTATGTCAACAAACGGAATACCACGTGGCAGGCCGGG
	CACAACTTCTACAACGTGGACATGAGCTACTTGAAGAGGCTATGTGGTACCTTCCTCGGTGGGCCCA
	AGCCACCCCAGAGAGTTATGTTTACCGAGGACCTGAAGCTGCCTGCAAGCTTCGATCCACGGGAACA
	ATGGCCACAGTGTCCCACCATCAAAGAGATCAGAGACCAGGGCTCCTCTGGCTCCTGCTGGGCCTTC
	GGGGCTGTGGAAGCCATCTCTGACCGGATCTGCATCCACACCAATGCGCACGTCAGCGTGGAGGTGT
	CGGCGGAGGACCPGCTCACATGCTGTGGCAGCATGTGTGGGGACGGCTGTAATGGTCGCTATCCTGC
	TGAAGCTTGCAACTTCTGGACAAGAAAAGGCCTCGTTTCTGGTGGCCTCTATGAATCCCATGTAGGG
	TGCAGACCGTACTCCATCCCTCCCTGTGAGCACCACGTCAACGGCTCCCGGCCCCCATGCACGGGGG
	AGGGAGATACCCCCAAGTGTAGCAAGATCTGTGAGCCTGGCTACAGCCCGACCTACAAACAGGACAA
	GCACTACGGATACAATTCCTACAGCGTCTCCAATAGCGAGAAGGACATCATGGCCGAGATCTACAAA
	AACGGCCCCGTGGAGGGAGCTTTCTCTGTGTATTCGGACTTCCTGCTCTACAAGTCAGGAGTGTACC
	AACACGTCACCGGAGAGATGATGGGTGGCCATGCCATCCGCATCCTGGGCTGGGGAGTGGAGAATGG
	CACACCCTACTGGCTGGTTGCCAACTCCTCGAACACTGACTGGGGTGACAATGGCTTCTTTAAAATA
	CTCAGAGGACAGGATCACTGTGGAATCGAATCAGAAGTGGTGGCTGGAATTCCACGCACCGATCAGT
	ACTGGGAAAAGATCTAATCTGCCGTGGGCCTGTCGTGCCAGTCCTGGGGGCGAGATCGCGGTA
	ORF Start: ATG at 137		ORF Stop: TAA at 1154
	SEQ ID NO: 196	339 aa	MW at 37821.3 kD
NOV49a,	MWQLWASLCCLLVLANARSRPSFHPLSDELVNYVNKRNTTWQAGHNFYNVDMSYLKRLCGTFLGGPK
CG56836-01
Protein Sequenc PPQRVMFTEDLKLPASFDAREQWPQCPTIKEIRDQGSCGSCWAFGAVEAISDRICIHTNAHVSVEVS
	AEDLLTCCGSMCGDGCNGGYPAEAWNFWTRKGLVSGCLYESHVGCRPYSIPPCEHHVNGSRPPCTGE
	CDTPKCSKICEPGYSPTYKQDKHYGYNSYSVSNSEKDIMAEIYKNGPVEGAFSVYSDFLLYKSGVYQ
	HVTGEMMGGHAIRILGWGVENGTPYWLVANSWNTDWGDNGFFKILRGQDUCGIESEVVAGIPRTDQY
	WEKI
	SEQ ID NO: 197	723 bp
NOV49b,	ACATGGTGGATCTAGGATCCGGCTTCCAACATGTGGCAGCTCTGGGCCTCCCTCTGCTGCCTGCTGG
CG56836-02
DNA Sequence TGTTGGCCAATGCCCGGAGCAGGCCCTCTTTCCATCCCCTGTCGGATGAGCTGGTCAACTATGTCAA
	CAAACGGAATACCACGTGGCAGGCCGGGCACAACTTCTACAACGTGGACATGAGCTACTTGAAGAGG
	CTATGTGGTACCTTCCTGGGTGGGCCCAAGCCACCCCAGAGAGTTATGTTTACCGAGGACCTGAAGC
	TGCCTGCAAGCTTCGATGCACGGGAACAATGGCCACAGTGTCCCACCATCAAAGAGATCAGAGACCA
	GGGCTCCTGTGGCTCCTGCTGGGCCTTCGCGGCTGTGGAAGCCATCTCTGACCGGATCTCCATCCAC
	ACCAATGCGCACGTCAGCGTGGAGGTGTCGGCGGAGGACCTGCTCACCTGCCTGCTCTACAAGTCAG
	GAGTGTACCAACACGTCACCGGAGAGATGATGGGTGGCCATGCCATCCGCATCCTGGGCTGGGGAGT
	GGAGAATGGCACACCCTACTGGCTGGTTGCCAACTCCTGGAACACTGACTGGGGTGACAATGGCTTC
	TTTAAAATACTCAGAGGACAGGATCACTGTGGAATCGAATCACAAGTGGTGGCTGGAATTCCACGCA
	CCGATCAGTACTGGGAAAAGATCTAATCTGCCGTGGGCCTGTCGTGCCAAACC
	ORF Start: ATG at 31		ORF Stop: TAA at 694
	SEQ ID NO: 198	221 aa	MW at 24974.2 kD
NOV49b,	MWQLWASLCCLLVLANARSRPSFHPLSDELVNYVNKRNTTWQAGUNFYNVDMSYLKRLCGTFLGGPK
CG56836-02
Protein Sequence	PPQRVMFTEDLKLPASFDAREQWPQCPTIKEIRDQGSCGSCWAFGAVEAISDRICIHTNAHVSVEVS
	AEDLLTCLLYKSGVYQHVTGEMMGGHAIRILGWGVENGTPYWLVANSWNTDWGDNGFFKILRCQDHC
	GIESEVVAGIPRTDQYWEKI
	SEQ ID NO: 199	1028 bp
NOV49c,	TGTAAGCGATCTGGTTCCCACCTCAGCCTCCCGAGTAGTCTCTTCAGGCCTATGGAGAGCAGCTTGC
CG56836-03
DNA Sequence	GTGGGCTGGGCCTGCAGTACCTGGTTTGCATAGATGATTGGCAGGTGGATCTACGATCCGGCTTCCA
	ACATGTGGCAGCTCTGCGCCTCCCTCTGCTGCCTGCTCGTGTTGGCCAATGCCCGGAGCAGGCCCTC
	TTTCCATCCCCTGTCGGATGAGCTGGTCAACTATGTCAACAAACGGAATACCACGTGGCAGGCCGGG
	CACAACTTCTACAACGTGCACATGAGCTACTTGAAGAGGCTATGTGGTACCTTCCTGGGTAAGCCCA
	AGCCACCCCAGAGAGTTATGTTTACCGAGCACCTGAAGCTGCCTGCAAGCTTCGATGCACGGGAACA
	ATGGCCACAGTGTCCCACCATCAAAGAGATCAGAGACCAGGGCTCCTGTGGCTCCTGCTGGGCCTTC
	GGGGCTGTGGAAGCCATCTCTGACCGGATCTGCATCCACACCAATGCGCACGTCAGCGTGGACGTGT
	CGGCGGAGGACCTCCTCACATGCTGTGGCAGCATGTGTGGCGACGGCTGTAATGGTGGCTATCCTGC
	TGAAGCTTGGAACTTCTGGACAAGAAAAGGCCTGGTTTCTGGTGCCCTCTATGAATCCAATAGCGAG
	AAGGACATCATGGCCGAGATCTACAAAAACGGCCCCGTGGAGGGAGCTTTCTCTGTGTATTCGGACT
	TCCTGCTCTACAAGTCAGGAGTGTACCAACACGTCACCGGAGAGATGATGGGTGGCCATGCCATCCG
	CATCCTGGGCTGGGGAGTGGAGAATGGCACACCCTACTGGCTGGTTGCCAACTCCTGGAACACTGAC
	TGGGGTGACAATGGCTTCTTTAAAATACTCAGAGGACAGGATCACTGTGGAATCGAATCAGAAGTGG
	TGGCTGGAATTCCACGCACCGATCAGTACTGGGAAAAGATCTAATCTGCCGTGGGCCTGTCGTGCCA
	GTCCTGGGGGCGAGATCGGGGTA
	ORF Start: ATG at 137		ORF Stop: TAA at 980
	SEQ ID NO: 200	281 aa	MW at 31423.2 kD
NOV49c,	MWQLWASLCCLLVLANARSRPSFHPLSDELVNYVNKRNTTWQAGHNFYNVDMSYLKRLCGTFLGGPK
CG56836-03
Protein Sequence	PPQRVMFTEDLKLPASFDAREQWPQCPTIKEIRDQGSCGSCWAFCAVEAISDRICIHTNAHVSVEVS
	AEDLLTCCGSMCGDGCNGGYPAEAWNFWTRKGLVSGGLYESNSEKDIMAEIYKNGPVEGAFSVYSDF
	LLYZSGVYQHVTGEMMGGNAIRILGWGVENGTPYWLVANSWNTDWGDNGFFKILRGQDHCGIESEVV
	AGIPRTDQYWEKI
	SEQ ID NO: 201	1028 bp
NOV49d,	TGTAAGCGATCTGGTTCCCACCTCAGCCTCCCGAGTAGTGTCTTCAGGCCTATGGAGAGCAGCTTGC
CG56836-04
DNA Sequence	GTCGGCTGCGCCTGCAGTACCTGGTTTGCATAGATGATTGGCAGGTGGATCTACGATCCGGCTTCCA
	ACATGTGGCAGCTCTGGGCCTCCCTCTGCTGCCTGCTGGTGTTGGCCAATGCCCGGAGCAGGCCCTC
	TTTCCATCCCCTGTCGGATGAGCTGGTCAACTATGTCAACAGACGGAATACCACGTGGCAGGCCGGG
	CACAACTTCTACAACGTGGACATGAGCTACTTGAAGAGGCTATGTCGTACCTTCCTGGGTGGGCCCA
	AGCCACCCCAGAGAGTTATGTTTACCGAGGACCTGAAGCTGCCTGCAAGCTTCGATGCACGGGAACA
	ATGGCCACAGTGTCCCACCATCAAAGAGATCAGAGACCAGGGCTCCTGTCGCTCCTGCTGGGTTTCT
	GGTGGCCTCTATGAATCCCATGTAGGGTGCAGACCGTACTCCATCCCTCCCTGTGAGCACCACGTCA
	ACGGCTCCCGGCCCCCATGCACGGGGGAGGCAGATACCCCCAAGTGTAGCAAGATCTGTGAGCCTGG
	CTACAGCCCGACCTACAAACAGGACAAGCACTACGGATACAATTCCTACACCGTCTCCAATAGCGAG
	AAGGACATCATGGCCGAGATCTACAAAAACGGCCCCGTGGAGGGAGCTTTCTCTGTGTATTCGGACT
	TCCTGCTCTACAAGTCAGGAGTGTACCAACACGTCACCGAAGAGATGATCGGTGGCCATGCCATCCG
	CATCCTGGGCTGGGGAGTGGAGAATGGCACACCCTACTGGCTGGTTGCCAACTCCTGGAACACTGAC
	TGGGGTGACAATGGCTTCTTTAAAATACTCAGAGGACAGGATCACTGTGGAATCGAATCAGAAGTGG
	TGGCTGGAATTCCACGCACCGATCAGTACTGGGAAAAGATCTAATCTGCCGTGGGCCTGTCGTGCCA
	GTCCTGGGGGCGAGATCGGGGTA
	ORF Start: ATG at 137		ORF Stop: TAA at 980
	SEQ ID NO: 202	281 aa	MW at 31732.5 kD
NOV49d,	MWQLWASLCCLLVLANARSRPSFHPLSDELVNYVNRRNTTWQAGHNFYNVDMSYLKRLCGTFLGGPK
CG56836-04
Protein Sequence	PPQRVMFTEDLKLPASFDAREQWPQCPTIKEIRDQGSCGSCWVSGGLYESHVGCRPYSIPPCEHHVN
	GSRPPCTGEGDTPKCSKICEPGYSPTYKQDKHYGYNSYSVSNSEKDIMAEIYKNGPVEGAFSVYSDF
	LLYKSGVYQHVTGEMMGGHAIRILGWGVENGTPYWLVANSWNTDWGDNGFFKILRGQDHCGIESEVV
	AGIPRTDQYWEKI
	SEQ ID NO: 203	340 bp
NOV49e,	AGGCTCCGCGGCCGCCCCCTTCACCGGATCCCPGCCTGCAAGCTTCGATGCACGGGAACAATGGCCA
247856403 DNA
Sequence	CAGTGTCCCACCATCAAAGAGATCAGAGACCAGGGCTCCTGTGACTCCTGCTGGGCCTTCGGGGCTG
	TGGAAGCCATCTCTGACCGGATCTGCATCCACACCAATGCGCACGTCAGCCTCGAGGTCTCGCCGGA
	GGACCTGCTCACATGCTGTGGCAGCATGTGTGGGGACGGCTGTAATGGTGGCTATCCTGCTGAAGCT
	TGGAACTTCTGGACAAGAAAAGGCCTGGTTTCTGGTGGCCTCTATCTCGAGGGCAAGGGTGGGCGCG
	CCGAC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO: 204	113 aa	MW at 11834.0 kD
NOV49e,	GSAAAPFTGSLPASFDAREQWPQCPTIKEIRDQGSCGSCWAFGAVEAISDRICIHTNAHVSVEVSAE
247856403
Protein Sequence	DLLPCCGSMCGDGCNGGYPAEAWNFWTRKGLVSGGLYLEGKGGRAD
	SEQ ID NO: 205	1376 bp
NOV49f,	AGGCTCCGCGGCCGCCCCCTTCACCGGATCCTCCAATAGCGAGAAGGACATCATGGCCGAGATCTAC
247856434 DNA
Sequence	AAAAACGGCCCCGTGCAGGGAGCTTTCTCTGTGTATTCGGACTTCCTGCTCTACAAGTCAGGAGTGT
	ACCAACACGTCACCGGAGAGATGATGGGTGGCCATGCCATCCCCATCCTGGGCTGGGGAGTGGAGAA
	TGGCACACCCTACTGGCTGGTTGCCAACTCCTGGAACACTGACTGGGGTGACAATGGCTTCTTTAAA
	ATACTCAGAGGACAGGATCACTGTGGAATCGAATCAGAAGTGGTGGCTGGAATTCCACGCACCGATC
	AGTACTGGGAAAAGATCCTCGAGGGCAAGGGTGGGCGCGCC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO: 206	125 aa	MW at 13666.1 kD
NOV49f,	GSAAAPFTGSSNSEKDIMAEIYKNGPVEGAFSVYSDFLLYKSGVYQHVTGEMMGGHAIRILGWGVEN
247856434
Protein Sequence	GTPYWLVANSWNTDWGDNGFFKILRGQDHCGIESEVVAGIPRTDQYWEKILEGKGGRA
	SEQ ID NO: 207	574 bp
NOV49g,	AGGCTCCGCGGCCGCCCCCTTCACCGGATCCATGTGGCAGCTCTGGGCCTCCCTCTGCTGCCTGCTG
247856497 DNA
Sequence	GTGTTGGCCAATGCCCGGAGCAGGCCCTCTTTCCATCCCCTGTCGGATGAGCTGGTCAACTATGTCA
	ACAAACGGAATACCACGTGGCAGGCCGGGCACAACTTCTACAACGTGGACATGAGCTACTTGAAGAG
	GCTATGTGGTACCTTCCTGGGTGGGCCCAAGCCACCCCAGAGAGTTATGTTTACCGAGGACCTGAAG
	CTGCCTGCAAGCTTCGATGCACGGGAACAATGGCCACAGTGTCCCACCATCAAAGAGATCAGAGACC
	AGGGCTCCPGTGGCTCCTGCTGGGCCTTCGGGGCTGTGGAAGCCATCTCTGACCGGATCTGCATCCA
	CACCAATGCGCACGTCAGCGTGGAGGTGTCGGCGGAGGACCTGCTCACATGCTGTGGCAGCATGTGT
	GGGGACGGCTGTAATGGTGGCTATCCTGCTGAAGCTTGAACTTCTGGAACAAGAAAAGGCCTGGTTT
	CTGGTGGCCTCTATCTCGAGGGCAAGGGTGGGCGCGCC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO: 208	191 aa	MW at 20877.5 kD
NOV49g,	GSAAAPFTGSMWQLWASLCCLLVLANARSRPSFHPLSDELVNYVNKRNTTWQAGHNFYNVDMSYLKR
247856497
Protein Sequence	LCGTGLGGPKPRQRVMFTEDLKLPASFDAREQWPQCPTIKEIRDQGSCGSCWAFGAVEAISDRICIH
	TNAHVSVEVSAEDLLTCCGSMCGDGCNGGYPAEAWNFWTRKGLVSGGLYLEGKGGRA
	SEQ ID NO: 209	590 bp
NOV49h,	AGGCTCCGCGGCCGCCCCCTTCACCGGATCCATGTGGCAGCTCTGGGCCTCCCTCTGCTGCCTGCTG
247856493 DNA
Sequence	GTGTTGGCCAATGCCCGGAGCAGGCCCTCTTTCCATCCCGTGTCGGATGAGCTGGTCAACTATGTCA
	ACAAACGGAATACCACGTGGCAGGCCGGGCACAACTTCTACAACGTGGACATGCGCTACTTCAAGAG
	GCTATGTGGTACCTTCCTCGGTCGGCCCAAGCCACCCCAGAGAGTTATGTTTACCGAGGACCTGAAG
	CTGCCTGCAAGCTTCGATGCACGGGAACAATGGCCACAGTGTCCCACCATCAAAGAGATCAGAGACC
	AGGGCTCCTGTGGCTCCTGCTGGGCCTTCGGCGCTGTGGAAGCCATCTCTGACCGGATCTGCATCCA
	CACCAATGCGCACGTCAGCGTGGAGGTGTCGGCGGAGGACCTGCTCACCTGCTGTGGCAGCATGTGT
	GGGGACGGCTGTAATGGTGGCTATCCTCCTGAAGCTTGGAACTTCTGGACAAGAAAAGGCCTGGTTT
	CTGGTGGCCTCTATCTCGAGGGCAAGGGTGGGCGCGCCGACCCAGCTTTCTGTA
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO: 210	197 aa	MW at 21367.0 kD
NOV49h,	GSAAAPFTGSMWQLWASLCCLLVLANARSRPSFHPVSDELVNYVNKRNTTWQAGHNFYNVDMGYLKR
247856493
Protein Sequence	LCGTFLGGPKPPQRVMFTEDLKLPASFDAREQWPQCPTIKEIRDQGSCGSCWAFGAVEAISDRICIH
	TNAHVSVEVSAEDLLTCCGSMCGDGCNGGYPAEAWNFWTRKGLVSGGLYLEGKGGRADPAFCX
	SEQ ID NO: 211	551 bp
NOV49i,	AGGCTCCGCGGCCGCCCCCTTCACCGGATCCCGGAGCAGGCCCTCTTTCCATCCCCTGTCGGATGAG
247856574 DNA
Sequence	CTGGTCAACTATGTCAACAAACGGAATACCACGTGGCAGGCCGCGCACAACTTCTACAACGTGGACA
	TGACCTACTTGAAGAGGCTATGTGGTACCTTCCTGGGTGGGCCCAAGCCACCCCAGAGAGTTATGTT
	TACCGAGGACCTGAAGCTGCCTGCAAGCTTCGATGCACGGGAACAATGGCCACAGTGTCCCACCATC
	AAAGAGATCAGAGACCAGGGCTCCTGTGGCTCCTGCTCGGCCTTCGGCGCTGTGGAAGCCATCTCTG
	ACCGGATCTGCATCCACACCAATGCGCACGTCAGCGTGGAGGTGTCGGCGGAGGACCTGCTCACATG
	CTGTGGCAGCATGTGTGGAGACGGCTGTAATGGTGGCTATCCTGCTGAAGCTTCGAACTTCTGGACA
	AGAAAAGGCCTGGTTTCTCGTGGCCTCTATCTCGAGGGCAAGGGTGGGCGCCCCGACCCAGCTTTCC
	CGTACAAAGCTGGCA
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO: 212	184 aa	MW at 19933.2 kD
NOV49i,	GSAAAPFTGSRSRPSFHPLSDELVNYVNKRNTTWQAGHNFYNVDMSYLKRLCGTFLGGPKPPQRVMF
247856574
Protein	TEDLKLPASFDAREQWPQCPTIKEIRDQGSCCSCWAFGAVEAISDRICIHTNAHVSVEVSAEDLLTC
Sequence
	CGSMCGDGCNGGYPAEAWNFWTRKGLVSGGLYLEGKGGRPDPAFPYKAGX
	SEQ ID NO: 213	523 bp
NOV49j,	AGGCTCCGCGGCCGCCCCCTTCACCGGATCCCGGAGCAGGCCCTCTTTCCATCCCCTGTCGGATCAG
247856545 DNA
Sequence	CTGGTCAACTATGTCAACAAACGGAATACCACGTGGCAGGCCGGGCACAACTTCTACAACGTGGACA
	TGAGCTACTTGAAGAGGCTATGTGGTACCTTCCTGGGTGGGCCCAAGCCACCCCTGAGACTTATGTT
	TACCGACGACCTGAAGCTGCCTGCAAGCTTCGATGCACGGGAACAATGGCCACAGTGTCCCACCATC
	AAAGAGATCAGAGACCAGGGCTCCTGTGGCTCCTGCTGGGCCTTCGGGGCTGTCGAAGCCATCTCTG
	ACCGGATCTGCATCCACACCAATGCGCACGTCAGCGTGGAGGTGTCGGCCCAGGACCTGCTCACATG
	CTGTGGCGGCATGTGTGGGGACGCCTGTAATGGTGGCTATCCTGCTGAAGCTTGGAACTTCTGGACA
	AGAAAAGGCCTGGTTTCTGGTGGCCTCTATCTCGAGGGCAAGGGTGGGCGCGCC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO: 214	174 aa	MW at 18915.1 kD
NOV49j,	GSAAAPFTGSRSRPSFHPLSDELVNYVNKRNTTWQAGHNFYNVDMSYLKRLCGTFLGGPKPPLRVMF
247856545
Protien	TEDLKLPASFDAREQWPQCPTIKEIRDQCSCGSCWAFGAVEAISDRICIHTNAHVSVEVSAEDLLTC
Sequence
	CGGMCCDCCNGGYPAEAWNFWTRKGLVSGGLYLEGKGGRA
	SEQ ID NO:215	1036 bp
NOV49k,	CACCCTCGAGATGTGGCAGCTCTGGGCCTCCCTCTGCTGCCTGCTGGTGTTGGCCAATGCCCGGACC
275480714 DNA
Sequence	AGGCCCTCTTTCCATCCCCTGTCGGATGACCTGGTCAACTATGTCAACAAACGCAATACCACGTGGC
	AGGCCGGGCACAACTTCTACAACGTGGACATGAGCTACTTGAAGAGGCTATGTGGTACCTTCCTGGG
	TGGGCCCAAGCCACCCCAGAGAGTTATGTTTACCGAGGACCTGAAGCTGCCTGCAAGCTTCGATGCA
	CGGGAACAATGGCCACAGTGTCCCACCATCAAAGAGATCAGAGACCAGGGCTCCTGTGGCTCCTGCT
	GGGCCTTCGGGGCTGTGGAAGCCATCTCTGACCGGATCTGCATCCACACCAATGCGCACGTCAGCGT
	GGAGGTGTCGGCGGAGGACCTGCTCACATGCTGTGGCAGCATGTGTGGGGACGGCTGTAATGGTGGC
	TATCCTGCTGAAGCTTGGAACTTCTGGACAAGAAAAGGCCTGGTTTCTGGTGGCCTCTATGAATCCC
	ATGTAGGGTGCAGACCGTACTCCATCCCTCCCTGTGAGCACCACGTCAACGGCTCCCGGCCCCCATC
	CACGGGGGAGGGAGATACCCCCAAGTGTAGCAAGATCTGTGAGCCTGGCTACAGCCCGACCTACAAA
	CAGGACAAGCACTACGGATACAATTCCTACAGCGTCTCCAATAGCGAGAAGGACATCATGGCCGAGA
	TCTACAAAAACCGCCCCGTGGAGGCAGCTTTCTCTGTGTATTCGGACTTCCTGCTCTACAAGTCAGG
	AGTGTACCAACACGTCACCGGAGAGATGATGGGTGGCCATGCCATCCGCATCCTGGGCTGGGGAGTG
	GAGAATGGCACACCCTACTGGCTGGTTGCCAACTCCTGGAACACTGACTGGGGTGACAATGCCTTCT
	TTAAAATACTCAGAGGACAGGATCACTGTGGAATCGAATCAGAAGTGGTGGCTGGAATTCCACGCAC
	CGATCAGTACTGGCAAAAGATCGTCGACGGC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO: 216	345 aa	MW at 38435.9 kD
NOV49k,	TLEMWQLWASLCCLLVLANARSRPSFHPLSDELVNYVNKRNTTWQAGHNFYWVDMSYLKRLCGTFLC
275480714
Protein Sequence	GPKPPQRVMFTEDLKLPASFDAREQWPQCPTIKEIRDQGSCGSCWAFGAVEAISDRICIHTNAHVSV
	EVSAEDLLTCCGSMCGDGCNGGYPAEAWNFWTRKGLVSGGLYESHVGCRPYSIPPCEHHVNGSRPPC
	TGEGDTPKCSKICEPGYSPTYKQDKHYGYNSYSVSNSEKDIMAEIYKNGPVEGAFSVYSDFLLYKSG
	VYQHVTGEMMCCHAIRILGWGVENGTPYWLVANSWNTDWGDNGFFKILRGQDHCGIESEVVAGIPRT
	DQYWEKIVDG

[0602] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 49B.

TABLE 49B
Comparison of NOV49a against NOV49b through NOV49k.
Protein	NOV49a Residues/	Identities/
Sequence	Match Residues	Similarities for the Matched Region
NOV49b	1 . . . 141	141/141 (100%)
	1 . . . 141	141/141 (100%)
NOV49c	1 . . . 176	175/176 (99%)
	1 . . . 176	176/176 (99%)
NOV49d	1 . . . 339	279/339 (82%)
	1 . . . 281	280/339 (82%)
NOV49e	80 . . . 180	96/101 (95%)
	11 . . . 111	96/101 (95%)
NOV49f	233 . . . 339	107/107 (100%)
	11 . . . 117	107/107 (100%)
NOV49g	1 . . . 180	175/180 (97%)
	11 . . . 190	175/180 (97%)
NOV49h	1 . . . 180	173/180 (96%)
	11 . . . 190	174/180 (96%)
NOV49i	17 . . . 181	159/165 (96%)
	10 . . . 174	160/165 (96%)
NOV49j	17 . . . 180	144/164 (87%)
	10 . . . 173	145/164 (87%)
NOV49k	1 . . . 339	339/339 (100%)
	4 . . . 342	339/339 (100%)

[0603] Further analysis of the NOV49a protein yielded the following properties shown in Table 49C.

TABLE 49C
Protein Sequence Properties NOV49a
PSort analysis:   0.3700 probability located in outside;
                  0.1900 probability located in lysosome
                  (lumen); 0.1376 probability located in
                  microbody (peroxisome); 0.1000 probability
                  located in endoplasmic reticulum (membrane)
SignalP analysis: Cleavage site between residues 18 and 19

[0604] A search of the NOV49a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 49D.

TABLE 49D
Geneseq Results for NOV49a
			Identities/
		NOV49a	Similarities for
Geneseq	Protein/Organism/Length	Residues/Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAR90616	Anti-procathepsin B	1 . . . 339	338/339 (99%)	0.0
	monoclonal antibody - Homo	1 . . . 339	339/339 (99%)
	sapiens, 339 aa.
	[JP07309900-A,
	28-NOV-1995]
AAB53470	Human colon cancer antigen	1 . . . 339	338/339 (99%)	0.0
	protein sequence SEQ ID:	6 . . . 344	338/339 (99%)
	NO: 1010 - Homo sapiens,
	344 aa. [WO200055351-A1,
	21-SEP-2000]
ABP41147	Human ovarian antigen	1 . . . 339	290/339 (85%)	0.0
	HOFMP73, SEQ ID:	8 . . . 346	317/339 (92%)
	NO: 2279 - Homo sapiens,
	346 aa. [WO200200677-A1,
	03-JAN-2002]
ABB06116	Human NS protein sequence	1 . . . 267	266/267 (99%)	e−167
	SEQ ID NO: 208 - Homo	1 . . . 267	266/267 (99%)
	sapiens, 273 aa.
	[WO200206315-A2,
	24-JAN-2002]
ABB65378	Drosophila melanogaster	13 . . . 331	190/330 (57%)	e−113
	polypeptide SEQ ID NO:	13 . . . 339	232/330 (69%)
	22926 - Drosophila
	melanogaster, 340 aa.
	[WO200171042-A2,
	27-SEP-2001]

[0605] In a BLAST search of public sequence datbases, the NOV49a protein was found to have homology to the proteins shown in the BLASTP data in Table 49E.

TABLE 49E
Public BLASTP Results for NOV49a
			Identities/
Protein		NOV49a	Similarities for
Accession		Residues/Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
P07858	Cathepsin B precursor (EC	1 . . . 339	338/339 (99%)	0.0
	3.4.22.1) (Cathepsin B1) (APP	1 . . . 339	339/339 (99%)
	secretase) - Homo sapiens
	(Human), 339 aa.
KHBOB	cathepsin B (EC 3.4.22.1)	1 . . . 335	280/335 (83%)	e−180
	precursor - bovine, 335 aa.	1 . . . 335	307/335 (91%)
P07688	Cathepsin B precursor (EC	1 . . . 335	279/335 (83%)	e−180
	3.4.22.1) - Bos taurus	1 . . . 335	307/335 (91%)
	(Bovine), 335 aa.
P00787	Cathepsin B precursor (EC	1 . . . 336	265/336 (78%)	e−175
	3.4.22.1) (Cathepsin B1)	1 . . . 336	299/336 (88%)
	(RSG-2) - Rattus norvegicus
	(Rat), 339 aa.
P10605	Cathepsin B precursor (EC	1 . . . 336	267/336 (79%)	e−174
	3.4.22.1) (Cathepsin B1) -	1 . . . 336	297/336 (87%)
	Mus musculus (Mouse), 339
	aa.

[0606] PFam analysis predicts that the NOV49a protein contains the domains shown in the Table 49F.

TABLE 49F
Domain Analysis of NOV49a
		Identities/
Pfam	NOV49a	Similarities	Expect
Domain	Match Region	for the Matched Region	Value
Peptidase_C1	80 . . . 329	112/344 (33%)	1.3e−117
		218/344 (63%)

Example 50

[0607] The NOV50 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 50A.

TABLE 50A
NOV50 Sequence Analysis
	SEQ ID NO: 217	960 bp
NOV50a,	CCCGTCCGAGCCCCGGCCCCAAGTAACGCCGCCGCCCCGGAGCCGCCTTGGAGGTCCCCCTCCCCAC
CG572840-01
DNA Sequence	TAAGTGCCTCTTTGCATACCACCAGTCCCCACCCGCACGCTCTCTGGACCACTACAGCTGGACGGGC
	AATGGCGGGTCGGGGAGGCGCACGACGACCCAATGGACCAGCTGCTGGGAACAAGATCTGTCAATTT
	AACCTGGTTCTGCTGGGGGAGTCTGCGGTAGGCAAATCCAGCCTCGTCCTCCGCTTTGTCAAGGGAC
	AGTTTCACGAGTACCAGGAGAGCACAATTGGAGCGGCCTTCCTCACACAGACTGTCTGCCTGGATGA
	CACAACAGTCAAGTTTGAGATCTGGGACACAGCTGGACAGGAGCGGTATCACAGCCTGGCCCCCATG
	TACTATCCGCGGGCCCAGGCTGCCATCGTGGTCTATGACATCACCAACACAGATACATTTGCACGGG
	CCAAGAACTGGGTGAAGGAGCTACAGAGCCAGGCCAGCCCCAACATCGTCATTGCACTCGCGGGTAA
	CAAGGCAGACCTGGCCACCAAGAGAGCCGTGGAATTCCAGGAAGCACAAGCCTATGCAGACGACAAC
	AGTTTGCTGTTCATGGAGACATCAGCAAAGACTGCAATGAACGTGAACGAAATCTTCATGGCAATAG
	CTAAGAAGCTTCCCAAGAACGAGCCCCAGAATGCAACTGGTGCTCCAGGCCGAAACCGAGGTGTGGA
	CCTCCAGGAGAACAACCCAGCCAGCCGGAGCCAGTGCTGCACCAACTGAGCCCCCCTTGCCTGCCCG
	CTGCCCCCGCCTCCTCCGCCTGAATGACCCGACTGGAATCCACTCTAACCAATCGCACTTAACGACT
	CGGGCCACCACTGGGGGGGCAGGGGGAGGGGTCCACCATGATTTCTCCATATAATTTTGATCATAGG
	CCGGAGTGAGTCATTCCACCTG
	ORF Start: ATG at 136		ORF Stop: TGA at 784
	SEQ ID NO: 218	216 aa	MW at 23567.4 kD
NOV50a,	MAGRGGARRPNGPAAGNKICQFKLVLLGESAVGKSSLVLRFVKGQFHEYQESTIGAAFLTQTVCLDD
CG57284-01
Protein Sequence	TTVKFEIWDTAGQERYHSLAPMYYRGAQAAIVVYDITNTDTFARAKNWVKELQRQASPNIVIALAGN
	KADLASKRAVEFQEAQAYADDNSLLFMETSAKTANNVNEIFMATAXKLPKNEPQNATGAPGRNRGVD
	LQENNPASRSQCCSN
	SEQ ID NO: 219	747 bp
NOV50b,	CCACTAAGTGCCTCTTTGCATAGCACCAGTCCCCACCCGCACGCTCTCTGGACCACTACAGCTGGAC
CG57284-03
DNA Sequence	GGGCAATGGCGGGTCGCGGAGGCGCAGCACGACCCAATGGACCAGCTGCTGGGAACAAGATCTGTCA
	ATTTAAGCTGGTTCTGCTGGGGGAGTCTGCGGTAGGCAAATCCAGCCTCGTCCTCCGCTTTGTCAAG
	GGACAGTTTCACGAGTACCAGGAGAGCACAATTGGAGCGGCCTTCCTCACACAGACTGTCTGCCTCG
	ATGACACAACAGTCAAGTTTGAGATCTGGGACACAGCTGGACAGGACCGGTATCACAGCCTGGCCCC
	CATGTACTATCGGGCGGCCCAGGCTGCCATCGTGGTCTATGACATCACCAACATCGTCATTGCGCTC
	GCGGGTAACAAGGCAGACCTGGCCAGCAAGAGAGCCGTCGAATTCCAGGAAGCACAAGCCTATGCAG
	ACGACAACACTTTGCTGTTCATGGAGACATCAGCAAAGACTGCAATGAACGTGAACGAAATCTTCAT
	GGCAATAGCTAAGAAGCTTCCCAAGAACGAGCCCCAGAATGCAACTCGTGCTCCACGCCGAAACCGA
	GGTGTGGACCTCCAGGAGAACAACCCAGCCAGCCGGAGCCACTGCTGCAGCAACTGAGCCCCCCTTG
	CCTGCCCGCTGCCCCCGCCTCCTCCGCCTCAATGACCCCACTGGAATCCACTCTAACCAATCGCACT
	TAACGACTCG
	ORF Start: ATG at 73		ORF Stop: TGA at 658
	SEQ ID NO: 220	195 aa	MW at 21039.6 kD
NOV50b,	MAGRGGAARPNGPAAGNKICQFKLVLLGESAVGKSSLVLRFVKGQFHEYQESTIGAAFLTQTVCLDD
CG57285-03	TTVKFEIWDTAGQERYHSLAPMYYRGAQAAIVVYDITNIVIALAGNKADLASKRAVEFQEAQAYADD
Protein Sequence	NSLLFMETSAKTAMNVNEIFMAIAKKLPKNEPQNATGAPGRNRGVDLQENNPASRSQCCSN
	SEQ ID NO: 221	819 bp
NOV50c,	AATCGCCTTCCACTAAGTGCCTCTTTGCATAGCACCAGTCCCCACCCGCACGCTCTCTGGACCACTA
CG57284-02	CAGCTGGACGGGCAATGGCGGGTCGGGGAGGCGCACCACGACCCAATGGACCAGCTGCTGGGAACAA
DNA Sequence	GATCTGTCAATTTAAGCTGGTTCTGCTGGGGGAGTCTGCGGTAGGCAAATCCAGCCTCGTCCTCCGC
	TTTGTCAAGGGACAGTTTCACGAGTACCAGGAGAGCACAATTGGAGCGGCCTTCCTCACACAGACTC
	TCTGCCTGGATGACACAACAGTCAAGTTTGAGATCTGGGACACAGCTGGACAGGAGCGGTATCACAG
	CCTGGCCCCCATGTACTATCGGGGGGCCCAGGCTGCCATCGTGGTCTATGACATCACCAACACAGAT
	ACATTTGCACGCGCCAAGAACTGGGTGAAGGAGCTACAGAGGCAGGCCAGCCCCAACATCGTCATTG
	CACTCGCGGGTAACAAGGCAGACCTGGCCAGCAAGAGAGCCGTGGAATTCCAGGAAGCACAAGCCTA
	TGCAGACGACAACAGTTTGCTGTTCATGGAGACATCAGCAAAGACTGCAATGAACGTGAACGAAATC
	TTCATGGCAATAGCTAACAAGCTTCCCAAGAACGAGCCCCAGAATGCAACTGGTGCTCCAGGCCGAA
	ACCGAGGTGTGGACCTCCAGGAGAACAACCCAGCCAGCCGGAGCCAGTGCTGCAGCAACTGAGCCCC
	CCTTGCCTGCCCCCTGCCCCCGCCTCCTCCGCCTGAATGACCCGACTGGAATCCACTCTAACCAATC
	GCACTTAACGACTCG
	ORF Start: ATG at 82		ORF Stop: TGA at 730
	SEQ ID NO: 222	216 aa	MW at 23482.3 kD
NOV50c,	MAGRGGAARPNGPAAGNXICQFKLVLLGESAVGKSSLVLRFVKGQEEEYQESTIGAAFLTQTVCLDD
CG57284-02	TTVKFEIWDTAGQERYHSLAPMYYRGAQAAIVVYDITNTDTFARAKNWVKELQRQASPNIVIALAGN
Protein Sequence	KADLASKRAVEFQEAQAYADDNSLLFMETSAKTAMNVNEIFMAIAKKLPKNEPQNATGAPGRNRGVD
	LQENNPASRSQCCSN

[0608] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 50B.

TABLE 50B
Comparison of NOV50a against NOV50b and NOV50c.
	NOV50a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV50b	18 . . . 216	178/199 (89%)
	18 . . . 195	178/199 (89%)
NOV50c	18 . . . 216	199/199 (100%)
	18 . . . 216	199/199 (100%)

[0609] Further analysis of the NOV50a protein yielded the following properties shown in Table 50C.

TABLE 50C
Protein Sequence Properties NOV50a
PSort analysis:   0.6500 probability located in cytoplasm; 0.2189
                  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

[0610] A search of the NOV50a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 50D.

TABLE 50D
Geneseq Results for NOV50a
			Identities/
		NOV50a	Similarities
	Protein/Organism/	Residues/	for the
Geneseq	Length	Match	Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAM79225	Human protein SEQ	9 . . . 216	179/208	e−101
	ID NO 1887 - Homo		(86%)
	sapiens, 215 aa.	8 . . . 215	194/208
	[WO200157190-A2,		(93%)
	09-AUG-2001]
AAY56173	Human Wnt-1	9 . . . 216	179/208	e−101
	amino acid		(86%)
	sequence - Homo	8 . . . 215	194/208
	sapiens, 215 aa.		(93%)
	[CA2200794-A,
	24-SEP-1998]
AAB28187	Human RAS-relates	1 . . . 197	178/197	9e−97
	protein RAB-5A -		(90%)
	Homo sapiens,	1 . . . 192	186/197
	193 aa.		(94%)
	[WO200052165-A2,
	08-SEP-2000]
AAM80209	Human protein SEQ	9 . . . 216	172/209	1e−95
	ID NO 3855 - Homo		(82%)
	sapiens, 255 aa.	47 . . . 255	189/209
	[WO200157190-A2,		(90%)
	09-AUG-2001]
ABB60036	Drosophila	2 . . . 214	159/213	8e−85
	melanogaster		(74%)
	polypeptide SEQ	11 . . . 218	177/213
	ID NO 6900 -		(82%)
	Drosophila
	melanogaster,
	219 aa.
	[WO200171042-A2,
	27-SEP-2001]

[0611] In a BLAST search of public sequence datbases, the NOV50a protein was found to have homology to the proteins shown in the BLASTP data in Table 50E.

TABLE 50E
Public BLASTP Results for NOV50a
			Identities/
		NOV50a	Similarities
Protein		Residues/	for the
Accession	Protein/Organism/	Match	Matched	Expect
Number	Length	Residues	Portion	Value
P51148	Ras-related protein	1 . . . 216	216/216	e−122
	Rab-5C (RAB5L)		(100%)
	(L1880) - Homo	1 . . . 216	216/216
	sapiens (Human),		(100%)
	216 aa.
AAM21086	Small GTP binding	1 . . . 216	215/216	e−121
	protein RAB5C -		(99%)
	Homo sapiens	1 . . . 216	215/216
	(Human), 216 aa.		(99%)
Q8R1V8	Hypothetical	1 . . . 216	212/216	e−119
	23.4 kDa protein -		(98%)
	Mus musculus	1 . . . 216	213/216
	(Mouse), 216 aa.		(98%)
P51147	Ras-related protein	1 . . . 216	212/216	e−119
	Rab-5C -		(98%)
	Canis familiaris	1 . . . 216	213/216
	(Dog), 216 aa.		(98%)
Q98932	Rab5C-like protein -	1 . . . 216	203/216	e−114
	Gallus gallus		(93%)
	(Chicken), 216 aa.	1 . . . 216	208/216
			(95%)

[0612] PFam analysis predicts that the NOV50a protein contains the domains shown in the Table 50F.

TABLE 50F
Domain Analysis of NOV50a
		Identities/
	NOV50a Match	Similarities for
Pfam Domain	Region	the Matched Region	Expect Value
arf	4 . . . 185	40/198 (20%)	0.0018
		105/198 (53%)
ras	23 . . . 216	90/209 (43%)	3.1e−104
		181/209 (87%)

Example 51

[0613] The NOV51 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 51A.

TABLE 51A
NOV51 Sequence Analysis
	SEQ ID NO: 223	4826 bp
NOV51a,	AGCTGAGCCCGAGCCCAGACCGCGCCCGCGCCGCCATGCCCCTGGCCTTCTGCGGCAGCGAGAACCA
CG57308-01
DNA Sequence	GTGCCGCACGTCTTCCTACTCTTCATCACCTTCCCCATCCTCTTCATTGGATGGGGAAGTCAGAGCT
	CCAAGGTGCACATCCACCACACCACATGGCTTCATTTCCCTGGCCACAACCTGCGGTGGATCCTGAC
	CTTCATGCTGCTCTTCGTCCTGGTGTGTGAGATTGCAGAGGGCATCCTGTCTGATGGGGTGACCGAA
	TCCCACCATCTGCACCTGTACATGCCAGCCGGGATGGCGTTCATGGCTGCTGTCACCTCCGTGGTCT
	ACTATCACAACATCGAGACTTCCAACTTCCCCAAGCTGCTAATTGCCCTGCTGGTGTATTGGACCCT
	GGCCTTCATCACCAAGACCATCAAGTTTGTCAAGTTCTTGGACCACGCCATCGGCTTCTCGCAGCTA
	CGCTTCTGCCTCACAGGGCTGCTGGTGATCCTCTATGGGATGCTGCTCCTCGTGGAGGTCAATGTCA
	TCAGGGTGACGAGATACATCTTCTTCAAGACACCGAGGGAGGTGAAGCCTCCCGAGGACCTGCAAGA
	CCTGGGGGTACGCTTCCTGCAGCCCTTCGTGAATCTGCTGTCCAAAGGCACCTACTGGTGGATGAAC
	GCCTTCATCAAGACTGCCCACAAGAAGCCCATCGACTTGCGAGCCATCGGGAAGCTGCCCATCGCCA
	TCAGGGCCCTCACCAACTACCAACGGCTCTGCGAGGCCTTTGACGCCCAGGTGCGGAAGGACATTCA
	GGGCACTCAAGGTGCCCGGGCCATCTGGCAGGCACTCAGCCATGCCTTCGGGAGCCGCCTGGTCCTC
	AGCAGCACTTTCCGCATCTTGGCCGACCTCCTGGGCTTCGCCGGGCCACTGTGCATCTTTGGGATCG
	TGGACCACCTTGGGAAGGAGAACCACGTCTTCCAGCCCAAGACACAATTTCTCGGGGTTTACTTTGT
	CTCATCCCAAGAGTTCCTTGCCAATGCCTACGTCTTAGCTGTGCTTCTGTTCCTTGCCCTCCTACTG
	CAAAGGACATTTCTGCAACCATCCTACTATGTGGCCATTGAAACTGGAATTAACTTGAGACGAGCAA
	TACAGACCAAGATTTACAATAAAATTATGCACCTGTCCACCTCCAACCTGTCCATGGGAGAAATGAC
	TGCTGGACAGATCTGTAATCTGGTTGCCATCGACACCAATCAGCTCATGTGGTTTTTCTTCTTGTGC
	CCAAACCTCTGGGCTATGCCAGTACAGATCATPGTGGGTGTGATTCTCCTCTACTACATACTCGGAG
	TCAGTGCCTTAATTGGAGCAGCTGTCATCATTCTACTGGCTCCTGTCCAGTACTTCGTGGCCACCAA
	GCTGTCTCAGGCCCAGCGCAGCACACTGGAGTATTCCAATGAGCGGCTGAAGCAGACCAACGAGATG
	CTCCGCGGCATCAAGCTGCTGAAGCTGTACGCCTGGGAGAACATCTTCCCCACGCGGGTGGAGACGA
	CCCGCAGGAAGGAGATGACCAGCCTCACGGCCTTTGCCATCTATACCTCCATCTCCATTTTCATGAA
	CACGGCCATCCCCATTGCAGCTGTCCTCATAACTTTCGTGGGCCATGTCAGCTTCTTCAAAGAGGCC
	GACTTCTCGCCCTCCGTGGCCTTTGCCTCCCTCTCCCTCTTCCATATCTTGGTCACACCGCTGTTCC
	TGCTGTCCAGTGTGGTCCGATCTACCGTCAAAGCTCTAGTGAGCGTGCAAAACCTAAGCGAGTTCCT
	GTCCAGTGCAGAGATCCGTGAGGAGCAGTGTGCCCCCCATGAGCCCACACCTCAGGGCCCAGCCAGC
	AAGTACCAGGCGGTGCCCCTCAGGGTTGTGAACCGCAAGCGTCCAGCCCGGGAGGATTGTCGGGGCC
	TCACCGGCCCACTGCAGAGCCTGGTCCCCAGTGCAGATGGCGATGCTGACAACTGCTGTGTCCAGAT
	CATGGGACGCTACTTCACGTGGACCCCAGATGGAATCCCCACACTGTCCAACATCACCATTCGTATC
	CCCCGAGGCCAGCTGACTATGATCGTGGGGCACGTGGGCTGCGGCAAGTCCTCGCTCCTTCTAGCCG
	CACTGGGGGAGATGCAGAAGGTCTCAGGGGCTGTCTTCTGGAGCAGCCTTCCTGACAGCGAGATAGG
	AGAGGACCCCAGCCCAGAGCGGGAGACAGCGACCGACTTGGATATCAGGAAGAGAGGCCCCGTGGCC
	TATGCTTCGCAGAAACCATGGCTGCTAAATGCCACTGTGGAGGAGAACATCATCTTTGAGAGTCCCT
	TCAACAAACAACGGTACAAGATGGTCATTGAAGCCTGCTCTCTGCAGCCAGACATCGACATCCTGCC
	CCATGGAGACCAGACCCAGATTGGGGAACGGGGCATCAACCTGTCTCGTGGTCAACGCCAGCGAATC
	AGTGTGGCCCGAGCCCTCTACCACCACGCCAACGTTGTCTTCTTGGATGACCCCTTCTCAGCTCTGG
	ATATCCATCTGAGTGACCACTTAATGCAGGCCGGCATCCTTGAGCTGCTCCGGGACGACAAGAGGAC
	AGTGGTCTTAGTGACCCACAAGCTACAGTACCTGCCCCATCCAGACTGGATCATTGCCATGAAGGAT
	GGCACCATCCAGAGGGAGGTACCCTCAAGAGACTTCCAGAGGTCTGAATGCCAGCTCTTTGAGCACT
	GGAAGACCCTCATGAACCGACACGACCAAGAGCTGGAGAAGGACACTGTCACAGAGAGAAAAGCCAC
	AGAGCCACCCCAGGGCCTATCTCGTGCCATGTCCTCGAGGGATGCCCTTCTGCAGGATGAGGAAGAG
	GAGGAAGAGGAGGCAGCTGAGAGCGAGGAGGATGACAACCTGTCGTCCATGCTGCACCAGCGTGCTG
	AGATCCCATGGCGAGCCTGCGCCAAGTACCTGTCCTCCGCCGGCATCCTGCTCCTGTCGTTGCTGGT
	CTTCTCACAGCTGCTCAAGCACATGGTCCTGGTGGCCATCGACTACTGCCTGGCCAAGTGGACCGAC
	AGCGCCCTGACCCTGACCCCTGCAGCCAGGAACTGCTCCCTCAGCCAGGAGTGCACCCTCGACCAGA
	CTGTCTATGCCATGGTCTTCACGGTGCTCTGCAGCCTGGGCATTGTCCTGTCCCTCGTCACGTCTGT
	CACTGTGGAGTGGACAAGGCTGAAGGTGGCCAAGAGACTGCACCGCAGCCTGCTAAACCGGATCATC
	CTAGCCCCCATGAGGTTTTTTGAGACCACGCCCCTTGGGAGCATCCTGAACAGATTTTCATCTGACT
	GTAACACCATCGACCAGCACATCCCATCCACGCTGGAGTGCCTGAGCCGCTCCACCCTGCTCTGTGT
	CTCAGCCCTGGCCGTCATCTCCTATGTCACACCTGTGTTCCTCGTGGCCCTCTTGCCCCTGGCCATC
	GTGTGCTACTTCATCCAGAAGTACTTCCGGGTGGCGTCCAGGGACCTGCAGCAGCTGGATGACACCA
	CCCAGCTTCCACTTCTCTCACACTTTGCCGAAACCGTAGAAGGACTCACCACCATCCGGGCCTTCAG
	GTATGAGGCCCGGTTCCAGCAGAAGCTTCTCGAATACACAGACTCCAACAACATTGCTTCCCTCTTC
	CTCACAGCTGCCAACAGATGGCTGGAAGTCCGAATGGAGTACATCGCTGCATGTGTGGTGCTCATCG
	CAGCCGTGACCTCCATCTCCAACTCCCTGCACAGCGAGCTCTCTGCTGGCCTGGTGGGCCTGGGCCT
	TACCTACGCCCTAATGGTCTCCAACTACCTCAACTGGATGGTGAGCAACCTGGCAGACATGGAGCTC
	CAGCTGCGCGCTGTGAAGCGCATCCATGGGCTCCTGAAAACCGAGGCAGAGAGCTACGAGGGGCTCC
	TGGCACCATCGCTGATCCCAAAGAACTGGCCAGACCAAGGGAAGATCCAGATCCAGAACCTGAGCGT
	GCGCTACGACACCTCCCTGAAGCCGGTGCTGAAGCACGTCAATGCCCTCATCTCCCCTGGACAGAAG
	ATCGGGATCTGCGGCCGCACCGGCAGTGGGAAGTCCTCCTTCTCTCTTGCCTTCTTCCGCATGGTGG
	ACACGTTCGAAGGGCACATCATCATTGATGGCATTGACATCGCCAAACTGCCGCTGCACACCCTGCC
	CTCACGCCTCTCCATCATCCTGCAGGACCCCGTCCTCTTCAGCGGCACCATCCGATTTAACCTCGAC
	CCTGAGAGGAAGTGCTCAGATAGCACACTGTGGGAGGCCCTGGAAATCGCCCAGCTGAAGCTCGTGG
	TGAAGGCACTGCCAGGAGGCCTCGATGCCATCATCACAGAAGGCGGGGAGAATTTCAGCCAGCGACA
	GAGGCAGCTGTTCTGCCTGGCCCGGGCCTTCGTGAGGAAGACCAGCATCTTCATCATGGACGAGGCC
	ACGGCTTCCATTGACATGGCCACGGAAAACATCCTCCAAAAGGTGGTGATGACAGCCTTCGCAGACC
	GCACTGTGGTCACCATCGCGCATCGAGTGCACACCATCCTGAGTGCAGACCTGGTGATCGTCCTGAA
	GCGGGGTGCCATCCTTGAGTTCGATAAGCCAGAGAAGCTGCTCAGCCGGAAGGACAGCGTCTTCGCC
	TCCTTCGTCCGTGCAGACAAGTGACCTGCCAGAGCCCAAGTCCCATCCCACATTCGGACCCTGCCCA
	TA
	ORF Start: ATG at 36		ORF Stop: TGA at 4779
	SEQ ID NO: 224	1581 aa	MW at 177005.9 kD
NOV51a,	MPLAFCGSENHSAAYRVDQGVLNNGCFVDALNVVPHVFLLFITFFILFIGWGSQSSKVHIHHSTWLH
CG57308-01
Protein Sequence	FPGHNLRWILTFMLLFVLVCETAECILSDGVTESHHLHLYMPAGMAFMAAVTSVVYYHNIETSNFPK
	LLIALLVYWTLAFITKTIKFVKFLDHAIGFSQLRFCLTGLLVILYGMLLLVEVNVIRVRRYIFFKTP
	REVKPPEDLQDLGVRFLQPFVNLLSKGTYWWMNAFIKTAHKKPIDLRAIGKLPIANRALTNYQRLCE
	AFDAQVRKDIOGTOGARAIWOALSHAFGRRLVLSSTFRILADLLGFAGPLCIFGIVDHLGKENDVFO
	PKTQFLGVYFVSSQEFLANAYVLAVLLFLALLLQRTFLQASYYVAIETGINLRGAIQTRIYNKIMHL
	STSNLSMGEMTACQICNLVAIDTNQLMWFFFLCPNLWAMPVQIIVGVILLYYILGVSALTGAAVTIL
	LAPVQYFVATKLSQAQRSTLEYSNERLKQTNEMLRGIKLLKLYAWENIFRTRVETTRRKEMTSLRAF
	AIYTSISIFMNTAIPIAAVLITFVGHVSFFKEADFSPSVAFASLSLFHILVTPLFLLSSVVRSTVKA
	LVSVQKLSEFLSSAEIREEQCAPHEPTPQGPASKYQAVPLRVVNRKRPAREDCRGLTGPLQSLVPSA
	DGDADNCCVQIMGGYFTWTPDGIPTLSNITIRIPRGQLTMIVGQVGCGKSSLLLAALGEMQKVSGAV
	FWSSLPDSEIGEDPSPERETATDLDIRKRGPVAYASQKPWLLNATVEENIIFESPFNKQRYKMVIEA
	CSLQPDTDILPHGDQTQIGERGINLSGGQRQRISVARALYQHANVVFLDDPFSALDIHLSDHLMQAG
	ILELLRDDKRTVVLVTHKLQYLPHADWIIAMKDGTTQREGTLKDFQRSECQLFEHWKTLNNRQDQEL
	EKETVTERKATEPPQGLSRAMSSRDGLLQDEEEEEEEAAESEEDDNLSSMLHQRAEIPWRACAKYLS
	SAGILLLSLLVFSQLLKHMVLVATDYWLAKWTDSALTLTPAARNCSLSQECTLDQTVYAMVFTVLCS
	LGIVLCLVTSVTVEWTGLKVAKRLHRSLLNRIILAPMRFFETTPLGSILNRFSSDCNTIDQEIPSTL
	ECLSRSTLLCVSALAVISYVTPVFLVALLPLAIVCYFIQKYFRVASRDLQQLDDTTQLPLLSHFAET
	VEGLTTIRAFRYEARFQQKLLEYTDSNNIASLFLTAANRWLEVRNEYIGACVVLIAAVTSISNSLHR
	ELSAGLVGLGLTYALMVSNYLNWMVRNLADMELQLCAVKRIHGLLKTEAESYEGLLAPSLIPKNWPD
	QCKIQIQNLSVRYDSSLKPVLKHVNALISPGQKIGICGRTGSGKSSFSLAFFRMVDTFEGHIIIDGI
	DIAKLPLHTLRSRLSIILQDPVLFSGTIRFNLDPERKCSDSTLWEALEIAQLKLVVKALPGGLDAII
	TEGGENFSQGQRQLFCLARAFVRKTSIFINDEATASIDMATENILQKVVMTAFADRTVVTIAHRVHT
	ILSADLVIVLKRGAILEFDKPEKLLSRKDSVFASFVRADK
	SEQ ID NO: 225	4745 bp
NOV51b,	CGGGGCCCGGGGGGCGGGGGCCTGACGGCCGGGCCGGGCGGCGGAGCTGCAAGGGACAGAGGCGCGG
CG57308-02
DNA Sequence	CACGCGCGCGGAGCCAGCGGAGCCAGCTGAGCCCGAGCCCAGCCCGCGCCCGCGCCGCCATGCCCCT
	GGCCTTCTGCGGCAGCGAGAACCACTCGGCCGCCTACCGGGTGGACCAGGGGGTCCTCAACAACGGC
	TGCTTTGTGGACGCGCTCAACGTGGTGCCGCACGTCTTCCTACTCTTCATCACCTTCCCCATCCTCT
	TCATTGGATGGGGAAGTCAGAGCTCCAAGGTGCACATCCACCACAGCACATGGCTTCATTTCCCCGG
	GCACAACCTGCGGTGGATCCTGACCTTCATGCTGCTCTTCGTCCTGGTGTGTCAGATTGCAGAGGGC
	ATCCTGTCTGATGGGGTGACCGAATCCCACCATCTGCACCTGTACATGCCAGCCGGGATCGCGTTCA
	TGGCTGCTGTCACCTCCGTGGTCTACTATCACAACATCGAGACTTCCAACTTCCCCAAGCTGCTAAT
	TGCCCTGCTGGTGTATTGGACCCTGGCCTTCATCACCAAGACCATCAAGTTTGTCAAGCTCTTGGAC
	CACGCCATCGGCTTCTCGCAGCTACGCTTCTGCCTCACAGGGCTGCTGGTGATCCTCTATGGGATGC
	TGCTCCTCGTGGAGGTCAATGTCATCAGGGTGACGAGATACATCTTCTTCAAGACACCGAGGGAGGT
	GAAGCCTCCCGAGGACCTGCAAGACCTGGGGGTACGCTTCCTGCAGCCCTTCGTGAATCTGCCGTCC
	AAACGCACCTACTGGTGGATGAACGCCTTCATCAAGACTGCCCACAAGAAGCCCATCGACTTGCGAG
	CCATCGGGAACCTGCCCATCGTTATGAGGGCCCTCACCAACTACCAACGGCTCTGCGAGGCCTTTGA
	CGCCCAGGTGCGGAAGGACATTCAGGGCACTCAAGGTGCCCGGGCCATCTGGCAGGCACTCAGCCAT
	GCCTTCGGGACGCGCCTGGTCCTCAGCAGCACTTTCCGCATCTTGGCCGACCTGCTGGGCTTCGCCG
	GCCACTGTCCATCTTTGGCATCGTGGACCACCTTGGGAAGGAGAAACGACGTCTTCCAGCCCAAGAC
	ACAATTTCTCGGGGTTTACTTTGTCTCATCCCAAGAGTTCCTTGCCAATGCCTACGTCTTAGCTGTG
	CTTCTGTTCCTTGCCCTCCTACTGCAAAGGACATTTCTGCAAGCATCCTACTATGTGGCCATTGAAA
	CTGGAATTAACTTGAGAGGAGCAATACAGACCAAGATTTACAATAAAATTATGCACCTGTCCACCTC
	CAACCTGTCCATGGGAGAAATGACTGCTGGACAGATCTGTAATCTGGTTGCCATCGACACCAATCAG
	CTCATGTGGTTTTTCTTCTTGTGCCCAAACCTCTGGGCTATGCCAGTACAGATCATTGTGGGTGTGA
	TTCTCCTCTACTACATACTCGGAGTCAGTGCCTTAATTGGAGCAGCTGTCATCATTCTACTGGCTCC
	TGTCCAGTACTTCGTGGCCACCAAGCTGTCTCAGGCCCAGCGGAGCACACTGGAGTATTCCAATGAG
	CGGCTGAGCAGACCAACGAGATCCTCCGCGGCATCAAGCTCCTGAAGCTGTACGCCTGGGAAGAACA
	TCTTCCGCACGCGGGTGGAGACGACCCGCAGGAAGGAGATGACCAGCCTCAGGGCCTTTGCCATCTA
	TACCTCCATCTCCATTTTCATGAACACGGCCATCCCCATTGCAGCTGTCCTCATAACTTTCGTGGGC
	CATGTCAGCTTCTTCAAAGAGGCCGACTTCTCGCCCTCCGTGGCCTTTGCCTCCCTCTCCCTCTTCC
	ATATCTTGGTCACACCGCTGTTCCTGCTGTCCAGTGTGGTCCGATCTACCGTCAAAGCTCTAGTGAG
	CGTGCAAAAGCTAAGCGAGTTCCTGTCCAGTGCAGAGATCCGTGAGGAGCAGTGTGCCCCCCATGAG
	CCCACACCTCAGGGCCCAGCCAGCAAGTACCAGGCGGTGCCCCTCAGGGTTGTGAACCGCAAGCGTC
	CAGCCCGGGAGGATTGTCGGGGCCTCACCGGCCCACTGCAGACCCTGGTCCCCAGTGCAGATGGCGA
	TGCTGACAACTGCTGTGTCCAGATCATGGCAGGCTACTTCACGTGGACCCCAGATGGAATCCCCACA
	CTGTCCAACATCACCATTCGTATCCCCCGAGGCCAGCTGACTATGATCGTGGGGCAGGTGGGCTCCG
	GCAAGTCCTCGCTCCTTCTAGCCGCACTGGGGGAGATGCAGAAGGTCTCAGGGGCTGTCTTCTGGAG
	CAGCCTTCCTGACAGCGAGATAGGAGAGGACCCCAGCCCAGAGCGGGAGACAGCGACCGACTTGGAT
	ATCAGGAAGAGAGGCCCCGTGGCCTATGCTTCGCAGAAACCATGGCTGCTAAATGCCACTGTGGAGG
	AGAACATCATCTTTGAGAGTCCCTTCAACAAACAACGGTACAAGATGGTCATTGAAGCCTGCTCTCT
	GCAGCCAGACATCGACATCCTGCCCCATGGAGACCAGACCCAGATTGGGGAACGGGGCATCAACCTG
	TCTGGTGGTCAACGCCACCGAATCAGTGTGGCCCGAGCCCTCTACCAGCACGCCAACGTTGTCTTCT
	TGGATGACCCCTTCTCAGCTCTGGATATCCATCTGAGTGACCACTTAATGCACGCCGGCATCCTTGA
	GCTGCTCCGGGACGACAAGAGGACAGTGGTCTTAGTGACCCACAAGCTACAGTACCTGCCCCATGCA
	GACTGGATCATTGCCATGAAGGATGGCACCATCCAGAGGGAGGGTACCCTCAAGGACTTCCAGAGGT
	CTGAATGCCAGCTCTTTGAGCACTGGAGACCCTCATGAACCGACAGGACCAAAGAGCTGGAGAAGGA
	GACTGTCACAGAGAGAAAACCCACAGAGCCACCCCAGGGCCTATCTCGTGCCATGTCCTCGAGGGAT
	GGCCTTCTGCAGGATGAGGAAGAGGAGGAAGAGGAGGCAGCTGAGAGCGAGGAGGATGACAACCTGT
	CGTCCATGCTGCACCAGCGTGCTGAGATCCCATGGCCAGCCTGCGCCAAGTACCTGTCCTCCGCCGG
	CATCCTGCTCCTGTCGTTGCTGGTCTTCTCACAGCTGCTCAAGCACATGGTCCTGGTGGCCATCGAC
	TACTGGCTGGCCAAGTGGACCGACAGCGCCCTGACCCTGACCCCTGCAGCCAGGAACTGCTCCCTCA
	GCCAGGAGTGCACCCTCGACCAGACTGTCTATGCCATCGTGTTCACGCTGCTCTGCAGCCTGGGCAT
	TGTGCTGTGCCTCGTCACGTCTGTCACTGTGGAGTGGACAGGGCTGAACGTCGCCAAGAGACTGCAC
	CGCAGCCTGCTAAACCGGATCATCCTAGCCCCCATGAGGTTTTTTGAGACCACCCCCCTTGGGAGCA
	TCCTGAACAGATTTTCATCTGACTGTAACACCATCGACCAGCACATCCCATCCACGCTAAAGTGCCT
	GAGCCGCTCCACCCTGCTCTGTGTCTCAGCCCTGGCCGTCATCTCCTATGTCACACCTGTGTTCCTC
	GTGGCCCTCTTGCCCCTGCCCATCGTGTGCTACTTCATCCAGAAGTACTTCCCGGTGGCGTCCAGGG
	ACCTGCAGCAGCTGGATGACACCACCCAGCTTCCACTTCTCTCACACTTTGCCGAAACCGTAGAAGG
	ACTCACCACCATCCGGGCCTTCAGGTATGAGGCCCGGTTCCAGCAGAACCTTCTCGAATACACAGAC
	TCCAACAACATTGCTTCCCTCTTCCTCAACAGCTGCCAACAGATGCTGGAAGTCCGAATGGAGTACA
	TCGGTGCATGTGTGGTGCTCATCGCAGCGGTGACCTCCATCTCCAACTCCCTGCACAGGGAGCTCTC
	TGCTGGCCTGGTGGGCCTGGGCCTTACCTACGCCCTAATGGTCTCCAACTACCTCAACTGGATGGTG
	AGGAACCTGGCAGACATGGAGCTCCAGCTCGGGGCTGTGAAGCGCATCCATGGGCTCCTGAAAACCG
	AGGCAGAGAGCTACGAGGGGCTCCTGGCACCATCGCTGAATCCCAAGAACTGGCCAGACCAAGGGAA
	GATCCAGATCCAGAACCTGAGCGTGCGCTACGACAGCTCCCTGAAGCCGGTGCTGAAGCACGTCAAT
	GCCCTCATCTCCCCTGGACAGAAGATCGGGATCTGCGGCCGCACCGGCAGTGGGAAGTCCTCCTTCT
	CTCTTGCCTTCTTCCGCATGGTGGACACGTTCGAAGGGACATCATCACAGAAGGCGGGGGAGAATTT
	CAGCCAGGGACAGAGGCAGCTGTTCTGCCTGGCCCGGGCCTTCGTGACGAAGACCAGCATCTTCATC
	ATGGACGAGGCCACCGCTTCCATTGACATGGCCACGGAAAAAACATCCTCCAAGCTAATGATGACAG
	CCTTCGCAGACCGCACTGTGGTCACCATCGCGCATCGAGTGCACACCATCCTGAGTGCAGACCTGGT
	GATCGTCCTGAGCGGGGTGCCATCCTTGAGTTCGATAAGCCAGAGAAGCTGCTCAGCCGGAAAGGAC
	AGCGTCTTCGCCTCCTTCGTCCGTGCAGACAAGTGACCTGCCAGAGCCCAAGTGCCATCCCACATTC
	GGACCCTGCCCATACCCCTGCCTGCGTTTTCTAACTGTAAATCACTTGTAAATAA
	ORF Start: ATG at 127		ORF Stop: TGA at 4657
	SEQ ID NO: 226	1510 aa	MW at 169179.9 kD
NOV51b,	MPLAFCGSENHSAAYRVDQGVLNNGCFVDALNVVPHVFLLFITFPILFIGWGSQSSKVHIHHSTWLH
CG57308-02
Protein Sequence	FPCHNLRWILTFMLLFVLVCEIAEGILSDGVTESHHLHLYMPAGMAFMAAVTSVVYYHNIETSNFPK
	LLIALLVYWTLAFITKTIKFVKLLDHTGFSQLRFCLTGLLVILYGMLLLVEVNVIRRVRRYIFFKTP
	REVKPPEDLQDLGVRFLQPFVNLPSKGTYWWMNAFIKTAHKKPIDLRAIGKLPIVMRALTNYQRLCE
	AFDAQVRKDIQGTQGARAIWQALSHAFGRRLVLSSTFRILADLLGFAGPLCIFGIVDHLGKENDVFQ
	PKTQFLGVYFVSSQEFLANAYVLAVLLFLALLIQRTFLQASYYVAIETGINLRGAIQTKIYNKIMHL
	STSNLSMGEMTAGQICNLVAIDTNQLMWFFFLCPNLWANPVQIIVGVILLYYILCVSALIGAAVIIL
	LAPVQYFVATKLSQAQRSTLEYSNERLKQTNEMLRGIKLLKLYAWENIFRTRVETTRRKEMTSLRAF
	AIYTSISIFMNTAIPIAAVLITFVGHVSFFKEADFSPSVAFASLSLFHILVTPLFLLSSVVRSTVKA
	LVSVQKLSEFLSSAEIREEQCAPHEPTPQGPASKYQAVPLRVVNRKRPAREDCRGLTGPLQSLVPSA
	DGDADNCCVQIMGGYFTWTPDGIPTLSNITIRIPRGQLTMIVGQVGCGKSSLLLAALCEMQKVSGAV
	FWSSLPDSEIGEDPSPERETATDLDIRKRGPVAYASQKPWLLNATVEENIIFESPFNKQRYKMVIEA
	CSLQPDIDILPHGDQTQIGERGTNLSGGQRQRISVARALYQHANVVFLDDPESALDIHLSDHLMQAG
	ILELLRDDKRTVVLVTHKLQYLPHADWIIAMKDGTIQREGTLKDFQRSECQLFEHWKTLMNRQDQEL
	EKETVTERKATEPPQGLSRAMSSRDGLLQDEEEEEEEAAESEEDDNLSSMLHQRAEIPWRACAKYLS
	SAGILLLSLLVFSQLLKHMVLVAIDYWLAKWTDSALTLTPAARNCSLSQECTLDQTVYAMVFTVLCS
	LGIVLCLVTSVTVEWTGLKVAKRLHRSLLNRIILAPMRFFETTPLGSILNRFSSDCNTIDQHIPSTL
	ECLSRSTLLCVSALAVISYVTPVFLVALLFLAIVCYEIQKYFRVASRDLQQLDDTTQLPLLSHFAET
	VEGLTTIRAFRYEARFQQKLLEYTDSNNIASLFLTAANRWLEVRMEYIGACVVLIAAVTSISNSLHR
	ELSAGLVGLGLTYALMVSNYLNWMVRNLADMELQLGAVKRIHGLLKTEAESYEGLLAPSLIPKNWPD
	QGKIQIQNLSVRYDSSLKPVLKHVNALISPGQKIGICGRTGSGKSSFSLAFFRMVDTFECHIITEGG
	ENFSQGQRQLFCLARAFVRKTSIFINDEATASIDMATENILQKVVMTAFADRTVVTIAHRVHTILSA
	DLVIVLKRGAILEFDKPEKLLSRKDSVFASFVRADK

[0614] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 51B.

TABLE 51B
Comparison of NOV51a against NOV51b.
	NOV51a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV51b	1 . . . 1406	1285/1406 (91%)
	1 . . . 1406	1286/1406 (91%)

[0615] Further analysis of the NOV51a protein yielded the following properties shown in Table 51C.

TABLE 51C
Protein Sequence Properties NOV51a
PSort analysis:   0.8000 probability located in plasma membrane;
                  0.4000 probability located in Golgi body; 0.3000
                  probability located in endoplasmic reticulum
                  (membrane); 0.3000 probability located in microbody
                  (peroxisome)
SignalP analysis: Cleavage site between residues 56 and 57

[0616] A search of the NOV51a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 51D.

TABLE 51D
Geneseq Results for NOV51a
			Identities/
		NOV51a	Similarities
	Protein/Organism/	Residues/	for the
Geneseq	Length	Match	Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAW57412	Homo sapiens	1 . . . 1581	1530/1582	0.0
	sulphonylurea		(96%)
	receptor - Homo	1 . . . 1580	1540/1582
	sapiens, 1580 aa.		(96%)
	[WO9814571-A1,
	09-APR-1998]
AAR77087	Rat sulphonylurea	1 . . . 1581	1477/1582	0.0
	receptor - Rattus		(93%)
	sp, 1582 aa.	1 . . . 1582	1509/1582
	[WO9528411-A1,		(95%)
	26-OCT-1995]
AAR77088	Hamster	1 . . . 1581	1469/1582	0.0
	sulphonylurea		(92%)
	receptor - Cricetus	1 . . . 1582	1506/1582
	sp, 1582 aa.		(94%)
	[WO9528411-A1,
	26-OCT-1995]
AAR77084	Rat sulphonylurea	1 . . . 1290	1195/1291	0.0
	receptor - Rattus		(92%)
	sp, 1498 aa.	1 . . . 1291	1223/1291
	[WO9528411-A1,		(94%)
	26-OCT-1995]
AAR77085	Hamster	1 . . . 1290	1186/1291	0.0
	sulphonylurea		(91%)
	receptor - Cricetus	1 . . . 1291	1220/1291
	sp, 1498 aa.		(93%)
	[WO9528411-A1,
	26-OCT-1995]

[0617] In a BLAST search of public sequence datbases, the NOV51a protein was found to have homology to the proteins shown in the BLASTP data in Table 51E.

TABLE 51E
Public BLASTP Results for NOV51a
			Identities/
		NOV51a	Similarities
Protein		Residues/	for the
Accession	Protein/Organism/	Match	Matched	Expect
Number	Length	Residues	Portion	Value
Q09428	Sulfonylurea	2 . . . 1581	1579/1580	0.0
	receptor 1 - Homo		(99%)
	sapiens (Human),	1 . . . 1580	1579/1580
	1580 aa.		(99%)
Q09429	Sulfonylurea	2 . . . 1581	1512/1582	0.0
	receptor 1 - Rattus		(95%)
	norvegicus (Rat),	1 . . . 1581	1536/1582
	1581 aa.		(96%)
Q09427	Sulfonylurea	2 . . . 1581	1498/1582	0.0
	receptor 1 -		(94%)
	Cricetus cricetus	1 . . . 1581	1530/1582
	(Black-bellied		(96%)
	hamster), 1581 aa.
A56248	sulfonylurea	1 . . . 1581	1469/1582	0.0
	receptor - golden		(92%)
	hamster, 1582 aa.	1 . . . 1582	1506/1582
			(94%)
Q95J92	Sulphonylurea	1 . . . 1580	1076/1581	0.0
	receptor 2B -		(68%)
	Oryctolagus	1 . . . 1548	1277/1581
	cuniculus		(80%)
	(Rabbit), 1549 aa.

[0618] PFam analysis predicts that the NOV51a protein contains the domains shown in the Table 51F.

TABLE 51F
Domain Analysis of NOV51a
	NOV51a Match	Identities/Similarities	Expect
Pfam Domain	Region	for the Matched Region	Value
ABC_membrane	318 . . . 590	53/287 (18%)	3.6e−46
		212/287 (74%)
ABC_tran	706 . . . 905	55/214 (26%)	1.3e−34
		154/214 (72%)
ABC_membrane	1011 . . . 1298	58/292 (20%)	2.7e−51
		222/292 (76%)
PRK	1374 . . . 1391	6/19  (32%)	0.21
		15/19  (79%)
ABC_tran	1371 . . . 1554	54/199 (27%)	5.7e−36
		129/199 (65%)

Example 52

[0619] The NOV52 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 52A.

TABLE 52A
NOV52 Sequence Analysis
	SEQ ID NO: 227	1404 bp
NOV52a,	ATGGAGTACATGAGCACTGGAAGTGACAATAAAGAAGAGATTGATTTATTAATTAAACATTTAAATG	~
CG93659-01
DNA Sequence	TGTCTGATGTAATAGACATTATGGAAAATCTTTATGCAAGTGAAGAGCCAGCAGTTTATGAACCCAG
	TCTAATGACCATGTGTCAAGACAGTAATCAAAACGATGAGCGTTCTAAGTCTCTGCTGCTTAGTGGC
	CAAGAGGTACCATGGTTGTCATCAGTCAGATATGGAACTGTGGAGGATTTGCTTGCTTTTGCAAACC
	ATATATCCACACTGCAAAGCATTTTTATGGAACAACGACCACAGGAATCTGGAATTTTATTAAACAT
	GGTCATCACTCCCCAAAATGGACGTTACCAAATAGATTCCGATGTTCTCCTGATCCCCTGGAAGCTG
	ACTTACAGGATATTGGTTCTGATTTTAAATTCCTCGGGGCGCCTTTGGAAGGTATACTTGGCTCAAG
	ATATAAAGACGAAGAAAAGAATGGCGTGTAAACTGATCCCAGTAGAACAATTTAAGCCATCTGATGT
	GGAAATTCAGGCTTGCTTCCGGCACGAGAACATCGCACAGCTGTATGGCGCAGTCCTGTGGGGTGAA
	ACTGTCCATCTCTTTATGGAAGCAGGCGAGGGAAGGGTCTGTTCTGGAGAACTGGAGAGCTCTAAAC
	CAATGAGAGAATTTGAAATTATTTGGGTGACAAAGCATGTTCTCAAGGGACTTGATTTTCTACACTC
	AAACAAGTGATCCATCATGATATTAAACCTAGCAACATTGTTTTCAATGTCCACAAAAGCTGTTTTG
	GTGGATTTTGGCCTAAGTGTTCAATGAACCGAAGATGTCTATTTTCCTAAGGACCTCCGAGGAACAG
	AGATTTACATGAGCCCAGAGGTCATCCTGTGCAGGGGCCATTCAACCAAGCAGACAATCTACAGCCT
	GGGGGCCACGCTCATCCACATGCAGACGGGCACCCCACCCTGGGTGAAGCGCTACCCTCGCTCAGCC
	TATCCCTCCTACCTGTACATAATCCACAAGCAAGCACCTCCACTGGAAGACATTGCAGATGACTGCA
	GTCCAGGGATGAGAGAGCTGATAGAAGCTTCCCTGGAGAGAAACCCCAATCACCCCCCAAGAGCCGC
	AGACCTACTAAAACATGAGGCCCTGAACCCGCCCAGAGAGGATCAGCCACGCTGTACGAGTCTGGAC
	TCTGCCCTCTTGGAGCGCAAGAGGCTGCTGAGTAGGAAGCAGCTGGAACTTCCTGAGAACATTGCTG
	ATTCTTCGTGCACACGAAGCACCGAGGAATCTGAGATGCTCAAGAGGCAACGCTCTCTCTACATCGA
	CCTCGGCGCTCTGGCTGGCTACTTCAATCTTGTTCGGCGACCACCAACGCTTGAATATGGCTGA
	ORF Start: ATG at 1		ORF Stop: TGA at 1402
	SEQ ID NO: 228	467 aa	MW at 52896.9 kD
NOV52a,	MEYMSTGSDNKEEIDLLIKHLNVSDVIDIMENLYASEEPAVYEPSLMTMCQDSNQNDERSKSLLLSG
CG93659-01
Protein Sequence	QEVPWLSSVRYGTVEDLLAFANHISNTKHFYGQRPQESGILLLNMVITPQNGRYQIDSDVLLIPWLK
	TYRNIGSDFIPRGAFGKVYLAQDIKTKKRMACKLIPVDQFKFSDVEIQACFRHENIAELYGAVLWGE
	TVHLFNEAGEGGSVLEKLESCGPMREFEIIWVTRHVLKGLDFLHSKKVIHHDIKPSNIVFNSTKAVL
	VDFGLSVQMTEDVYFPKDLRGTEIYMSPEVILCRGHSTKADIYSLGATLIHMQTGTPPWVKRYPRSA
	YPSYLYIIHKQAPPLEDIADDCSPGMRELIEASLERNPNHRPRAADLLKHEALNPPREDQPRCTSLD
	SALLERKRLLSRKELELPENIADSSCTGSTEESEMLKRQRSLYIDLGALAGYFNLVRGPPTLEYG
	SEQ ID NO: 229	1430 bp
NOV52b,	CTGACACTGCACTGAGCACTTTATGAGCTTGAACTCTGTTAATCCTCACGACCACCTCATGAGACTC
CG93659-03
DNA Sequence	TCCAGAAGAGCAACAGTAATGGAGTACAATGAGCACTGGAAGTGACAATAAAGAAGAGATTGATTTA
	TTAATTAAACATTTAAATGTGTCTGATGTAATAGACATTAATGGAATCTTTATGCAAAGTGAAGAGC
	CAGCAGTTTATGAACCCAGTCTAATGACCATGTGTCAAGACAGTAATCAAAACGATGAGCGTTCTAA
	GTCTCTGCTGCTTAGTGGCCAAGAGGTACCATGGTTGTCATCAGTCAGATACGGAACTGTGGAGGAT
	TTGCTTGCTTTTGCAAACCATATATCCAACACTGCAAAGCATTTTTATGGACAACGACCACAGGAAT
	CTGGAATTTTATTAAACATGGTCATCACTCCCCAAAATAAACGTTACCAAATAGATTCCGATGTTCT
	CCTGATCCCCTGCAAGCTGACTTACAGGAATATTGGTTCTGATTTTATTTCTCGGGGCGCCTTTAAA
	AAGGTATACTTGGCACAAGATATAAAGACGAAGGAAAAGAATGGCGTGTAACTGATCCCAGTAGATC
	ATTTAAGCCATCTGATGTGGAAATCCAAGGCTTGCTTCCGGCACGAGAACATCGCAGAGCTGTATAA
	CGCAGTCCTGTCGGGTGAAACTGTCCATCTCTTTATGGAAGCAGGCGAGGGAGGGTCTGTTCTGGAG
	AAACTGGAGAGCTGTGGACCAATGAGAGAATTTGAAATTAATTTGGGTGACAAGCATGTTCTCAAGG
	GACTTGATTTTCTACACTCAAAGAAAGTGATCCATCATGATATAAACATTTACATGAGCCCAGAGGT
	CATCCTGTGCAGGGGCCATTCAACCAAAGCAGACATCTACAGCCTGGGGGCCACGCTCATCCACATG
	CAGACGGGCACCCCACCCTGGGTGAAGCGCTACCCTCGCTCAGCCTATCCCTCCTACCTGTACATAA
	TCCACAAGCAAGCACCTCCACTGGAAGACATTGCAGATGACTGCAGTCCAGGGATGAGAGAGCTGAT
	AGAAGCTTCCCTGGAGAGAAACCCCAATCACCGCCCAAGAGCCGCAGACCTACTAAAACATGAGGCC
	CTGAACCCGCCCAGAGAGGATCAGCCACGCTGTCACAGTCTGGACTCTGCCCTCTTGGAGCGCAAGA
	GGCTGCTGAGTAGGAAGGAGCTGGAACTTCCTGAGAACATTGCTGATTCTTCGTGCACAGGAACCAC
	CGAGGAATCTGAGATGCTCAAGAGGCAACGCTCTCTCTACATCGACCTCGCCGCTCTGGCTGGCTAC
	TTCAATCTTGTTCGGGGACCACCAACGCTTGAATATGGCTGAAGGATGCCATGTTTGCTCTAAATTA
	AGACAGCATTGATCTCCTGGAGG
	ORF Start: ATG at 87		ORF Stop: TGA at 1380
	SEQ ID NO: 230	431 aa	MW at 48882.2 kD
NOV52b,	MEYMSTGSKNKEEIDLLIKHLNVSDVIDIMENLYASEEPAVYEPSLMTMCQDSNQNDERSKSLLLSG
CG93659-03
Protein Sequence	QEVPWLSSVRRYGTVEDLLAFAHISNTAKHFYGQRPQESGILLNMVITPQNGRYQIDSDVLLIPWKL
	TYRNIGSDFISRGAFGKVYLAQDIKTKKRMACKLIPVDQFKPSDVEIQACFRHENIAELYGAVLWGE
	TVHLFMEAGEGGSVLEKLESCGPMREFEIIWVTKHVLKGLDFLHSKKVIHHDINIYMSPEVILCRGH
	STKADIYSLGATLIHMQTGTPPWVKRYPRSAYPSYLYIIHKQAPPLEDIADDCSPGMRELIEASLER
	NPNHRPRAADLLKHEALNPPREDQPRCQSLDSALLERKRLLSRKELELPENIADSSCTCSTEESEML
	KRQRSLYIDLGALAGYFNLVRGPPTLEYG
	SEQ ID NO: 231	1538 bp
NOV52c,	CTGACACTGCACTGAGCACTTTATGAGCTTCAACTCTGTTAATCCTCACGACCACCTCATGAGACTC
CG93659-02
DNA Sequence	TCCAGAAAGAGCAACAGTAATGGAGTACATGAGCACTGGAAGTGACAATAAAGAAGAGATTGATTTA
	TTAATTAAACATTTAAATGTGTCTGATGTAATAGACATTATGGAAAATCTTTATGCAAGTGAAGAGC
	CAGCAGTTTATGAACCCAGTCTAATGACCATGTGTCAAAGACAGTAATCAAACGATGAGCGTTCTAA
	GTCTCTGCTGCTTAGTGGCCAAGACGTACCATGGTTGTCATCAGTCAGATACGGAACTGTGGACGAT
	TTGCTTGCTTTTGCAAACCATATATCCAACACTGCAAAGCATTTTTATGGACAACGACCACAGGAAT
	CTGGAATTTTATTAAACATGGTCATCACTCCCCAAAATGGACGTTACCAAATAGATTCCGATGTTCT
	CCTGATCCCCTGGAAGCTGACTTACAGGAATATTGGTTCTGATTTTATTTCTCGGGGCGCCTTTGGA
	AAGGTATACTTGGCACAAGATATAAAGACGAAGAAAAGAATGGCGTGTAAACTGATCCCAGTAGATC
	ATTTAAGCCATCTGATGTGGAAATCCAGGCTTGCTTCCGGCACAAAGAACATCGCAGAGCTGTATAA
	CGCAGTCCTGTGGGGTCAAACTGTCCATCTCTTTATGGAAGCAGGCGAGGGAGGGTCTGTTCTGGAG
	AAACTGGAGAGCTGTGGACCAATGAGAGAATTTAAAAATTATTTGGGTGACAGCATGTTCTCAAAGG
	GACTTCATTTTCTACACTCAGAAAGTAAAATCCACCATGATATTAAACCTAGCAACATTGTTTTCAT
	GTCCACAAAAGCTGTTTTGGTGGATTTTGGCCTAAGTGTTCAAAGACCGAAAGATGTCTATTTTCCT
	AAGGACCTCCGAGGAACAGAGATTTACATGAGCCCACAGGTCATCCTGTGCAGTGGCCATTCAACCA
	AGCACACATCTACAGCCTGGGGGCCACGCTCATCCACATGCAGACGGGCAACCCCACCCTGAATGAA
	GCGCTACCCTCGCTCAGCCTATCCCTCCTACCTGTACATAATCCACAAGCAAGCACCTCCACTGGAA
	GACATTGCAGATGACTGCAGTCCAGGGATGAGAGAGCTGATAGAAGCTTCCCTGGAGAGAAACCCCA
	ATCACCGCCCAAGAGCCGCAGACCTACTAAAACATGAGGCCCTGAACCCGCCCAGAGAAAATCAGCC
	ACGCTGTCAGAGTCTGGACTCTGCCCTCTTGGAGCGCAAGAGGCTGCTGAGTAGGAAGGAGCTGGAA
	CTTCCTGAGAACATTGCTGATTCTTCGTGCACAGGAAGCACCGAGGAATCTGAGATGCTCAACAGGC
	AACGCTCTCTCTACATCGACCTCGGCGCTCTGGCTGGCTACTTCAATCTTGTTCGGGGACCACCAAC
	GCTTGAATATGGCTGAAGGATGCCATGTTTGCTCTAAATTAAGACAGCATTGATCTCCTGGAGG
	ORF Start: ATG at 87		ORF Stop: TGA at 1488
	SEQ ID NO: 232	467 aa	MW at 52844.7 kD
NOV52c,	MEYMSTGSDNKEEIDLLIKHLNVSDVIDIMENLYASEEPAVYEPSLMTMCQDSNQNDERSKSLLLSG
CG93659-02
Protein Sequence	QEVPWLSSVRYGTVEDLLAFANHISNTAKHFYGQRPQESGILLNMVITPQNGRYQIDSDVLLIPWKL
	TYRNIGSDFISRGAFGKVYLAQDIKTKKRMACKLIPVDQFKPSDVEIQACFRHENIAELYGAVLWGE
	TVHLFMEAGEGGSVLEKLESCGPMREFEIIWVTKHVLKGLDFLHSKXVIHHDIKPSNIVFMSTKAVL
	VDFGLSVQMTEDVYFPKDLRGTEIYMSPEVILCSGHSTKADIYSLGATLIHMQTGTPPWVKRYPRSA
	YPSYLYIIHKQAPPLEDIADDCSPGMRELIEASLERNPNHRPRAADLLKHEALNPPREDQPRCQSLD
	SALLERKRLLSRKELELPENIADSSCTGSTEESEMLKRQRSLYIDLGALAGYFNLVRGPPTLEYG

[0620] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 52B.

TABLE 52B
Comparison of NOV52a against NOV52b and NOV52c.
	NOV52a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV52b	1 . . . 467	413/467 (88%)
	1 . . . 431	413/467 (88%)
NOV52c	1 . . . 467	449/467 (96%)
	1 . . . 467	449/467 (96%)

[0621] Further analysis of the NOV52a protein yielded the following properties shown in Table 52C.

TABLE 52C
Protein Sequence Properties NOV52a
PSort analysis:   0.6500 probability located in cytoplasm; 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

[0622] A search of the NOV52a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 52D.

TABLE 52D
Geneseq Results for NOV52a
			Identities/
		NOV52a	Similarities
	Protein/Organism/	Residues/	for the
Geneseq	Length	Match	Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAE05951	Human cot	1 . . . 467	467/467	0.0
	oncoprotein encoded		(100%)
	by D14497	1 . . . 467	467/467
	oncogene - Homo		(100%)
	sapiens, 467 aa.
	[US6265216-B1,
	24-JUL-2001]
AAY79244	Human COT -	1 . . . 467	467/467	0.0
	Homo sapiens,		(100%)
	467 aa.	1 . . . 467	467/467
	[WO200011191-A2,		(100%)
	02-MAR-2000]
AAE10313	Human Tp12	1 . . . 467	466/467	0.0
	protein - Homo		(99%)
	sapiens, 467 aa.	1 . . . 467	466/467
	[WO200166559-A1,		(99%)
	13-SEP-2001]
AAE10314	Rat Tp12 protein -	1 . . . 467	439/467	0.0
	Rattus sp, 467 aa.		(94%)
	[WO200166559-A1,	1 . . . 467	454/467
	13-SEP-2001]		(97%)
AAY79243	Rat TPL-2 - Rattus	1 . . . 467	438/467	0.0
	norvegicus, 467 aa.		(93%)
	[WO200011191-A2,	1 . . . 467	453/467
	02-MAR-2000]		(96%)

[0623] In a BLAST search of public sequence datbases, the NOV52a protein was found to have homology to the proteins shown in the BLASTP data in Table 52E.

TABLE 52E
Public BLASTP Results for NOV52a
			Identities/
		NOV52a	Similarities
Protein		Residues/	for the
Accession	Protein/Organism/	Match	Matched	Expect
Number	Length	Residues	Portion	Value
P41279	Mitogen-activated	1 . . . 467	467/467	0.0
	protein kinase kinase		(100%)
	kinase 8 (EC 2.7.1.-)	1 . . . 467	467/467
	(COT proto-oncogene		(100%)
	serine/threonine-protein
	kinase) (C-COT)
	(Cancer Osaka thyroid
	oncogene) - Homo
	sapiens (Human), 467 aa.
A48713	serine/threonine-specific	1 . . . 467	466/467	0.0
	protein kinase cot, 58K		(99%)
	form - human, 467 aa.	1 . . . 467	466/467
			(99%)
Q63562	Mitogen-activated	1 . . . 467	438/467	0.0
	protein kinase kinase		(93%)
	kinase 8 (EC 2.7.1.-)	1 . . . 467	453/467
	(Tumor progression		(96%)
	locus 2) (TPL-2) - Rattus
	norvegicus (Rat), 467 aa.
Q07174	Mitogen-activated	1 . . . 467	435/467	0.0
	protein kinase kinase		(93%)
	kinase 8 (EC 2.7.1.-)	1 . . . 467	454/467
	(COT proto-oncogene		(97%)
	serine/threonine-protein
	kinase) (C-COT) (Cancer
	Osaka thyroid
	oncogene) - Mus
	musculus (Mouse),
	467 aa.
A41253	kinase-related	1 . . . 397	379/397	0.0
	transforming protein (EC		(95%)
	2.7.1.-) - human, 415 aa.	1 . . . 397	379/397
			(95%)

[0624] PFam analysis predicts that the NOV52a protein contains the domains shown in the Table 52F.

TABLE 52F
Domain Analysis of NOV52a
	NOV52a Match	Identities/Similarities	Expect
Pfam Domain	Region	for the Matched Region	Value
pkinase	146 . . . 388	74/279 (27%)	4.7e−54
		187/279 (67%)

Example 53

[0625] The NOV53 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 53A.

TABLE 53A
NOV53 Sequence Analysis
	SEQ ID NO: 233	1078 bp
NOV53a,	GCGGCTACATTCGGCCCGGCCATGGCAGCGGCGCCCCTGAAAGTGTGCATCGTGGGCTCGGGGAACT
CG94521-01
DNA Sequence	GGGGTTCAGCTGTTGCAAAAATAATTGGTAATAACGTCAAGAAACTTCAGAAATTTGCCTCCACAGT
	CAAGATGTGCGTCTTTGAAGAAACAGTGAATGGCAGAAAACTGACAGACATCATAATAAATGACCAT
	GAAAATGTAAAATATCTTCCTGGACACAAGCTGCCAGAAAATGTGGTTCCCATGTCAAATCTTAGCG
	AGGCTGTGCAGGATGCAGACCTGCTGGTGTTTGTCATTCCCCACCAGTTCATTCACAGAATCTGTGA
	TGAGATCACTGGGAGAGTGCCCAAGAAGCGCTGGGAATCACCCTCATCAAAAGCATAAGACGAGGCC
	CCCGAGGGGCTGAAACTCATTTCTGACATCATCCCTGAGAAGATGGGTATTGACATCAGTGTGCTGA
	TGGGAGCCAACATTGCCAATGAGGTGGCTGCAGAGAAGTTCTGTGAGACCACCATCGGCAGCAAAGT
	AATGGAGAACGCCCTTCTCTTCAAAGAACTTCTGCAGACTCCAAATTTTCGAATTACGGTGGTTGAT
	GATGCAGACACTGTTGAACTCTGTGGTGCGCTTAAGAACATCGTAGCTGTGGGAGCTAAGTTCTGCG
	ACGGCCTCCGCTCTCGACACAACACCAAAGCGGCCGTCATCCGCCTGGGACTCATGGAAATGATTGC
	TTTTGCCAGGATCTTCTGCAAAGGCCAAGTGTCTACAGCCACCTTCCTAGAGAGCTGCAGGGTGGCC
	GACCTGATCACCACCTGTTACGGAGGGCGGAACCGCAGGGTGGCCGAGGCCTTCGCCAGAACTGGGA
	AGACCATTGAAGAGTTGGAGAAGGAGATGCTGAATGGGCAAAAGCTCCAAGGACCGCAGACTTCTGC
	TGAAGTGTACCGCATCCTCAAACAGAAGGGACTACTGGACAAGTTTCCATTGTTTACTGCAGTGTAT
	CAGATCTGCTACGAAAGCAGACCAGTTCAAGAGATGTTGTCTTGTCTTCAGAGCCATCCAGAGCATA
	CATAAA
	ORF Start: ATG at 22		ORF Stop: TAA at 1075
	SEQ ID NO: 234	351 aa	MW at 38418.3 kD
NOV53a,	MAAAPLKVCIVGSGNWGSAVAKIIGNNVKKLQKFASTVKMWVFEETVNGRKLTDIINNDHENVKYLP
CG94521-01
Protein Sequence	GHKLPENVVAMSNLSEAVQDADLLVFVIPHQFIHRICDEITGRVPKKALGITLIKGIDEGPEGLKLI
	SDIIREKMGIDISVLMGANIANEVAAEKFCETTIGSKVMENGLLFKELLQTPNFRITVVDDADTVEL
	CGALKNIVAVGAGFCDGLRCGDNTKAAVIRLGLMEMIAFARIFCKGQVSTATFLESCGVADLITTCY
	GGRNRRVAEAFARTGKTIEELEKEMLNGQKLQGPQTSAEVYRILKQKGLLDKFPLFTAVYQICYESR
	PVQEMLSCLQSHPEHT
	SEQ ID NO: 235	936 bp
NOV53b,	TACATTCGGCCCGGCCATGGCAGCGGCGCCCCTGAAAGTGTGCATCGTGGGCTCGGGGAACTGGGGT
CG94521-03
DNA Sequence	TCAGCTGTTGCAAAAATAATTGGTAATAATGTCAAGAAACTTCAGAAATTTGCCTCCACAGTCAAGA
	TGTGGGTCTTTGAAGAACAGTGAAATGGCAGAAAACTGACAGACATCATAAATAATGACCATGAAAA
	TGTAAAATATCTTCCTGGACACAAGCTGCCAGAAAATGTGCGCATAGACGAGGGCCCCGAGGAACTG
	AAGCTCATTTCTGACATCATCCGTGAGAAGATGGGTATTGACATCAGTGTGCTGATGGGAGCCAACA
	TTGCCAATGAGGTGGCTGCAGAGAAGTTCTGTGAGACCACCATCGGCAGCAAAGGAATGCAGAACGG
	CCTTCTCTTCAAGAACTTCTGCAGACTCCAAATTTTCGAATTACCCTGAATTGATGATGCAGACACT
	GTTGAACTCTGTGGTCCGCTTAAGAACATCGTAGCTGTGGGAGCTGGGTTCTGCGACGGCCTCCGCT
	GTGGAGACAACACCAAAGCGGCCGTCATCCGCCTGGGACTCATGGAAATGATTGCTTTTGCCAGGAT
	CTTCTGCAAAGGCCAAGTGTCTACAGCCACCTTCCTAGAGAGCTGCGGGGTGGCCGACCTGATCACC
	ACCTGTTACGGAGGGCCGGACCGCAGGGTGGCCGAGGCCTTCGCCAGAACTGGGAAGACCATTGAAG
	AGTTGGAGAAGGAGATCCTGAATGGGCAAAAGCTCCAAGGACCGCAGACTTCTGCTGAAGTGTACCG
	CATCCTCAAACAGAAGGGACTACTGGACAAGTTTCCATTGTTTACTGCACTGTATCAGATCTGCTAC
	GAAAGCAGACCAGTTCAAGAGATGTTGTCTTGTCTTCAGAGCCATCCAGAGCATACATAAAAAGG
	ORF Start: ATG at 17		ORF Stop: TAA at 929
	SEQ ID NO: 236	304 aa	MW at 33235.2 kD
NOV53b,	MAAAPLKVCIVGSGNWGSAVAKIIGNNVKKLQKFASTVKMWVFEETVNGRKLTDIINNDHENVKYLP
CG94521-03
Protein Sequence	GHKLPENVGIDEGPEGLKLISDIIREKMGIDISVLMGANIANEVAAEKFCETTIGSKVMENGLLFKE
	LLQTPNFRITVVDDADTVELCGALKNIVAVGAGFCDGLRCGDNTKAAVIRLGLMEMIAFARIFCKGQ
	VSTATFLESCGVADLTTTCYGGRNRRVAEAEARTGKTIEELEKEMLNGQKLQGPQTSAEVYRILKQK
	GLLDKFPLFTAVYQICYESRPVQEMLSCLQSHPEHT
	SEQ ID NO: 237	1077 bp
NOV53c,	TACATTCGGCCCGGCCATGGCACCGGCGCCCCTGAAACTGTGCATCGTGGGCTCCGCGAACTGGGGT
CG94521-02
DNA Sequence	TCAGCTGTTGCAAAAATAATTGCTAATAATGTCAAGAAACTTCAGAAATTTGCCTCCACAGTCAAGA
	TGTGGGTCTTTGAAGAAACAGTGAATGGCAGAAAACTGACAGACATCATAAATAATGACCATGAAAA
	TGTAAAATATCTTCCTGGACACAAGCTGCCAGAAAATGTGGTTGCCATGTCAAATCTTAGCGAGGCT
	GTGCAGGATGCAGACCTGCTGGTGTTTGTCATTCCCCACCAGTTCATTCACAGAATCTGTGATGAGA
	TCACTGGGAGAGTGCCCAAGAAAGCGCTCGGAATCACCCTCATCAAGGGCATAGACGAGGGCCCCGA
	GGGGCTGAAGCTCATTTCTGACATCATCCGTGAGAAGATGGGTATTGACATCAGTGTGCTGATGGGA
	GCCAACATTGCCAATGAGGTGGCTGCAGAGAAGTTCTGTGAGACCACCATCGGCAGCAAAGTAATGG
	AGAACGGCCTTCTCTTCAAAGAACTTCTGCAGACTCCAAATTTTCGAATTACCGTGGTTGATGATGC
	AGACACTGTTGAACTCTGTGGTGCGCTTAAGAACATCGTAGCTGTGGGAGCTGGGTTCTGCGACGGC
	CTCCGCTGTGGAGACAACACCAAAGCGGCCGTCATCCGCCTGGGACTCATCGAAATGATTGCTTTTG
	CCAGGATCTTCTGCAAAGGCCAAGTGTCTACAGCCACCTTCCTAGAGAGCTGCGGGGTGGCCGACCT
	GATCACCACCTGTTACCCAGGGCGGAACCGCAGGGTGGCCGAGGCCTTCGCCAGAACTGGGAAGACC
	ATTGAAGAGTTGGAGAAGGAGATGCTGAATGGGCAAAAGCTCCAAGGACCGCAGACTTCTGCTGAAG
	TGTACCGCATCCTCAAACAGAAGGGACTACTGGACAAGTTTCCATTGTTTACTGCAGTGTATCAGAT
	CTGCTACGAAAGCACACCAGTTCAAGAGATGTTGTCTTGTCTTCAGAGCCATCCAGAGCATACATAA
	AAAGG
	ORF Start: ATG at 17		ORF Stop: TAA at 1070
	SEQ ID NO: 238	351 aa	MW at 38418.3 kD
NOV53c,	MAAAPLKVCIVGSGNWCSAVAKIIGNNVKKLQKFASTVKMWVFEETVNGRKLTDIINNDHENVKYLP
CG94521-02
Protein Sequence	GHKLPENVVAMSNLSEAVQDADLLVFVTPHQFIHRICDEITGRVPKKALGITLIKGIDEGPEGLKLI
	SDITREKMGIDISVLMGANIANEVAAEKFCETTIGSKVMENGLLFKELLQTPNFRITVVDDADTVEL
	CGALKNIVAVGAGFCDGLRCGDNTKAAVIRLGLMEMIAFARIFCKGQVSTATFLESCGVADLITTCY
	GGRNRRVAEAFARTGKTIEELEKEMLNGQKLQGPQTSAEVYRILKQKGLLDKFPLFTAVYQICYESR
	PVQEMLSCLQSHPEHT

[0626] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 53B.

TABLE 53B
Comparison of NOV53a against NOV53b and NOV53c.
			Identities/
	Protein	NOV53a Residues/	Similarities for the
	Sequence	Match Residues	Matched Region
	NOV53b	1 . . . 351	304/351 (86%)
		1 . . . 304	304/351 (86%)
	NOV53c	1 . . . 351	351/351 (100%)
		1 . . . 351	351/351 (100%)

[0627] Further analysis of the NOV53a protein yielded the following properties shown in Table 53C.

TABLE 53C
Protein Sequence Properties NOV53a
PSort     0.6500 probability located in cytoplasm;
analysis: 0.1000 probability located in
          mitochondrial matrix space; 0.1000
          probability located in lysosome (lumen);
          0.0000 probability located in endoplasmic
          reticulum (membrane)
SignalP   Cleavage site between residues 22 and 23
analysis:

[0628] A search of the NOV53a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 53D.

TABLE 53D
Geneseq Results for NOV53a
		NOV53a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
ABB64184	Drosophila melanogaster	3 . . . 350	212/349 (60%)	e−120
	polypeptide SEQ ID NO	2 . . . 349	263/349 (74%)
	19344 - Drosophila
	melanogaster, 360 aa.
	[WO200171042-A2,
	27 SEP. 2001]
AAG08446	Arabidopsis thaliana protein	7 . . . 331	180/329 (54%)	8e−95
	fragment SEQ ID NO: 5988 -	22 . . . 349	233/329 (70%)
	Arabidopsis thaliana, 366 aa.
	[EP1033405-A2,
	06 SEP. 2000]
AAG08445	Arabidopsis thaliana protein	7 . . . 331	180/329 (54%)	8e−95
	fragment SEQ ID NO: 5987 -	56 . . . 383	233/329 (70%)
	Arabidopsis thaliana, 400 aa.
	[EP1033405-A2,
	06 SEP. 2000]
AAG08444	Arabidopsis thaliana protein	7 . . . 331	180/329 (54%)	8e−95
	fragment SEQ ID NO: 5986 -	77 . . . 404	233/329 (70%)
	Arabidopsis thaliana, 421 aa.
	[EP1033405-A2,
	06 SEP. 2000]
AAG39422	Arabidopsis thaliana protein	7 . . . 331	180/329 (54%)	1e−94
	fragment SEQ ID NO: 48774 -	22 . . . 349	232/329 (69%)
	Arabidopsis thaliana, 366
	aa. [EP1033405-A2,
	06 SEP. 2000]

[0629] In a BLAST search of public sequence datbases, the NOV53a protein was found to have homology to the proteins shown in the BLASTP data in Table 53E.

TABLE 53E
Public BLASTP Results for NOV53a
		NOV53a
Protein		Residues/	Identities/
Accession		Match	Similarities for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
AAH28726	KIAA0089 protein - Homo	1 . . . 351	351/351 (100%)	0.0
	sapiens (Human), 351 aa.	1 . . . 351	351/351 (100%)
Q14702	KIAA0089 protein - Homo	1 . . . 351	351/351 (100%)	0.0
	sapiens (Human), 411 aa	61 . . . 411	351/351 (100%)
	(fragment).
O57656	Glycerol-3-phosphate	3 . . . 350	265/349 (75%)	e−155
	dehydrogenase [NAD+],	2 . . . 350	306/349 (86%)
	cytoplasmic (EC 1.1.1.8)
	(GPD-C) (GPDH-C) - Fugu
	rubripes (Japanese
	pufferfish) (Takifugu
	rubripes), 351 aa.
Q98SJ9	Glycerol-3-phosphate	7 . . . 350	258/345 (74%)	e−152
	dehydrogenase (EC 1.1.1.8) -	5 . . . 349	301/345 (86%)
	Salmo salar (Atlantic
	salmon), 350 aa.
AAH32234	Glycerol-3-phosphate	4 . . . 350	249/347 (71%)	e−149
	dehydrogenase 1 (soluble) -	2 . . . 348	297/347 (84%)
	Homo sapiens (Human), 349
	aa.

[0630] PFam analysis predicts that the NOV53a protein contains the domains shown in the Table 53F.

TABLE 53F
Domain Analysis of NOV53a
		Identities/
		Similarities
Pfam	NOV53a Match	for the	Expect
Domain	Region	Matched Region	Value
NAD_Gly3P_dh	5 . . . 344	167/365 (46%)	2.1e−184
		307/365 (84%)

Example 54

[0631] The NOV54 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 54A.

TABLE 54A
NOV54 Sequence Analysis
	SEQ ID NO: 239	1552 bp
NOV54a,	TTATTCCCCACTTTACCTGGCTAATTGAAGTGTAACAAAAGCTTCATCCAGGAACATTCGCGCGGGA
CG96613-01
DNA Sequence	AACCTGGCGTACTGGCTGTGGCTTCTCTAGCGGGACTCGGCATGAGGCTGGCGCGGCTGCTTCGCGG
	AGCCGCCTTGGCCGGCCCGGGCCCGGGGCTGCGCGCCGCCGGCTTCAGCCGCAGCTTCAGCTCGGAC
	TCGGGCTCCAGCCCGGCGTCCGACCGCGGCGTTCCGGGCCAAATGGACTTCTACGCGCGCTTCTCGC
	CGTCCCCGCTCTCCATGAAGCAGTTCCTGGACTTCGGATCAGTGAATGCTTGTGAAAAGACCTCATT
	TATGTTTCTGCGCCAAGAGTTGCCTCTCAGACTGCCAAATATAATGAAAGAAATAAGTCTCCTTCCA
	GATAATCTTCTCAGGACACCATCCGTTCAATTGGTACAAAGCTGGTATATCCAGACTCTTCAGGAGC
	TTCTTGATTTTAAGGACAAAAGTGCTCAGGATGCTAAAGCTATTTATGACTTTACAGATACTGTGAT
	ACGGATCAGAAACCGACACAATGATGTCATTCCCACAATGGCCCAGGGTGTGATTCAATACAAGGAG
	AGCTTTGGCGTGGATCCTGTCACCAGCCAGAATGTTCAGTACTTTTTGGATCGATTCTACATGAGTC
	GCATTTCAATTAGAATGTTACTCAATCAGCACTCTTTATTGTTTGGTGGAAAAGGCAAAGGAAGTCC
	ATCTCATCGAAAACACATTCGAAGCATAAATCCAAACTGCAATGTACTTGAAGTTATTAAAGATGGC
	TATGAAAATGCTAGGCGTCTGTCTGATTTGTATTATATTAACTCTCCCGAACTAGAACTTGAAGAAC
	TAAATGCAAAATCACCAGGACACCCAATACAAGTGGTTTATGTACCATCCCATCTCTATCACATGGT
	GTTTGAACTTTTCAAGAATGCAATGACAGCCACTATGGAACACCATGCCAACAGAGGTGTTTACCCC
	CCTATTCAAGTTCATGTCACGCTGGGTAATGAGGATTTGACTGTGAAGATGAGTGACCGAGGAGGTG
	GCGTTCCTTTGAGGAAAATTGACAGACTTTTCAACTACATGTATTCAACTGCACCAAGACCTCGTGT
	TGAGACCTCCCGCGCAGTGCCTCTGCCTGGTTTTGGTTATGGATTGCCCATATCACGTCTTTACGCA
	CAATACTTCCAAGCAGACCTGAAGCTGTATTCCCTAGAGGGTTACGGGACAGATGCAGTTATCTACA
	TTAAGGCTCTGTCAACAGACTCAATAGAAAGACTCCCAGTGTATAACAAAGCTGCCTGGAACCATTA
	CAACACCAACCACGACGCTGATGACTGGTGCGTCCCCAGCAGAGAACCCAAAGACATGACGACGTTC
	CGCAGTGCCTAGACACACTGGGGACATCGGAAAATCCAAATGTGGCTTTTGTATTAAATTTGGAAGG
	TATGGTGTTCAGAACTATATTATACCAAGTACTTTATTTATCGTTTTCACAAAACTATTTGAGTAGA
	ATAAATGCAAA
	ORF Start: ATG at 109		ORF Stop: TAG at 1417
	SEQ ID NO: 240	436 aa	MW at 49243.6 kD
NOV54a,	MRLARLLRGAALAGPGPGLRAAGFSRSFSSDSGSSPASERGVPGQVDFYARFSPSPLSMKQFLDFGS
CG96613-01
Protein Sequence	VNACEKTSFMFLRQELPVRLANIMXEISLLPDNLLRTPSVQLVQSWYTQSLQELLDFKDKSAEDAKA
	IYDFTDTVIRIRNRHNDVIPTMAQGVIEYKESFGVDPVTSQNVQYFLDRFYMSRISIRMLLNQHSLL
	FGGKGKGSPSHRKHIGSINPNCNVLEVIKDGYENARRLCDLYYINSPELELEELNAKSPCQPIQVVY
	VPSHLYTHMVFELFKNMRATMEHHANRGVYPPIQVHVTLGNEDLTVKMSDRGGGVPLRKIDRLFNYM
	YSTAPRPRVETSRAVPLAGFGYGLPISRLYAQYFQGDLKLYSLEGYGTDAVIYIKALSTDSIERLPV
	YNKAAWXHYNTNHEADDWCVFSREPKDMTTFRSA
	SEQ ID NO: 241	1612 bp
NOV54b,	TTATTCCCCACTTTACCTGGCTAATTGAAGTGTAACAAAAGCTTCATCCACGAACATTGGCGCGGGA
CG96613-03
DNA Sequence	AACCTGGCGTACTGGCTGTGGCTTCTCTAGCGGGACTCGGCATGAGGCTGGCGCGGCTGCTTCGCGG
	AGCCGCCTTGGCCCGCCCGGGCCCGGGGCTGCGCGCCGCCCGCTTCAGCCGCAGCTTCAGCTCGGAC
	TCGGGCTCCAGCCCGGCGTCCGAGCGCGGCCTTCCGGGCCAGGTGGACTTCTACGCGCGCTTCTCGC
	CGTCCCCGCTCTCCATGAACCAGTTCCTGGACTTCGGATCAGTGAATGCTTGTGAAAAGACCTCATT
	TATGTTTCTGCGGCAAGAGTTGCCTGTCAGACTGGCAAATATATGAAAGAAATAAAGTCTCCTTCCA
	GATAATCTTCTCAGGACACCATCCGTTCAATTGGTACAAAGCTGGTATATCCAGAGTCTTCAGGAGC
	TTCTTGATTTTAAGGACAAAGTGCTGAGGATGCTAAAGCTATTTATGAAAAGGCCTAGAAGAACATG
	GTTGCAGGTCTCTAGTTTATGCTGTATGGCCTGCAAGATGATCTTTACAGATACTGTGATACGGATC
	AGAAACCGACACAATGATGTCATTCCCACAATGGCCCAGGCTGTGATTGAATACAAGGAGAGCTTTG
	GGGTGGATCCTGTCACCAGCCAGAATGTTCAGTACTTTTTGGATCGATTCTACATGAGTCGCATTTC
	AATTAGAATGTTACTCAATCAGCACTCTTTATTGTTTGGTGGAAAAGGCAAAGGAAGTCCATCTCAT
	CGAAACACATTGGAAGCATAAATCCAAACTGCAATGTACTTGAAAGTTATTAAACATGGCTATGAAA
	ATGCTAGGCGTCTGTGTGATTTGTATTATATTAACTCTCCCGAACTAGAACTTGAAGAACTAAATGC
	AAAATCACCAGGACAGCCAATACAAGTGGTTTATGTACCATCCCATCTCTATCACATGGTGTTTGAA
	CTTTTCAAGAATGCAATGAGAGCCACTATGGAACACCATGCCAACAGAGGTGTTTACCCCCCTATTC
	AAGTTCATGTCACGCTGGATAATGAGGATTTGACTGTGAAGATGAGTGACCGAGGAGGTGGCGTTCC
	TTTGAGGAAAATTGACAGACTTTTCAACTACATGTATTCAACTGCACCAAGACCTCGTGTTGAGACC
	TCCCGCGCAGTGCCTCTGGCTGGTTTTGGTTATGGATTGCCCATATCACGTCTTTACGCACAATACT
	TCCAACGAGACCTGAAGCTGTATTCCCTAGAGGGTTACGGGACAGATGCACTTATCTACATTAACGC
	TCTGTCAACAGACTCAATAGAAAGACTCCCAGTGTATAACATAGCTGCCTGGAAGCATTACAACACC
	AACCACGAGGCTGATGACTGGTGCGTCCCCAGCAGAGAACCCAAAGACATCACGACGTTCCGCAGTG
	CCTAGACACACTGGGGACATCGGAAAATCCAAATGTGGCTTTTGTATTAAATTTGGAAGGTATGGTG
	TTCAGAACTATATTATACCAAGTACTTTATTTATCGTTTTCACAAAACTATTTGAGTAGAATAAATG
	GAAA
	ORF Start: ATG at 109		ORF Stop: TAG at 1477
	SEQ ID NO: 242	456 aa	MW at 51622.6 kD
NOV54b,	MRLARLLRGAALAGPGPGLRAAGFSRSFSSDSGSSPASERGVPGQVDFYARFSPSPLSMKQFLDFGS
CG96613-03
Protein Sequence	VNACEKTSFMFLRQELPVRLANIMKEISLLPDNLLRTPSVQLVQSWYIQSLQELLDFKDKSAEDAKA
	IYERPRRTWLQVSSLCCMACKMIFTDTVIRIRNRHNDVIPTMAQGVIEYKESFGVDPVTSQNVQYFL
	DRFYMSRISIRMLLNQHSLLFGGKGKGSPSHRKHIGSINPNCNVLEVIKDGYENARRLCDLYYINSP
	ELELEELNAKSPGQPTQVVYVPSHLYHMVFELFKNANRATMEHHANRGVYPPIQVHVTLGNEDLTVK
	MSDRGGGVPLRKIDRLFNYMYSTAPRPRVETSRAVPLAGFGYGLPISRLYAQYFQGDLKLYSLEGYG
	TDAVIYIKALSTDSIERLPVYNKAAWKHYNTNHEADDWCVPSREPKDMTTFRSA
	SEQ ID NO: 243	967 bp
NOV54c,	TTATTCCCCACTTTACCTGGCTAATTGAAGTGTAACAAAAGCTTCATCCAGGAACATTGGCGCGGGA
CG96613-02
DNA Sequence	AACCTGGCGTACTGGCTGTGGCTTCTCTAGCGGGACTCGGCATGAGGCTGGCGCGGCTGCTTCGCGG
	AGCCGCCTTGGCCGGCCCGGGCCCGGGCCTGCGCGCCGCCGGCTTCAGCCGCAGCTTCAGCTCGGAC
	TCGGGCTCCAGCCCGGCGTCCGAGCGCGGCGTTCCGGGCCAGGTGGACTTCTACGCGCGCTTCTCGC
	CGTCCCCGCTCTCCATGAAGCAGTTCCTGGACTTCGGATCAGTCAATGCTTGTCAAAAGACCTCATT
	TATGTTTCTGCGGCAAGAGTTGCCTCTCAGACTGGCAAATATAATGAAAGAAATAAGTCTCCTTCCA
	GATAATCTTCTCAGGACACCATCCGTTCAATTGGTACAAAGCTGGTATATCCAGAGTCTTCAGGAGC
	TTCTTGATTTTAAGGACAAAAGTGCTGAGGATGCTAAAGCTATTTATGAAAGGCCTAGAACAACATG
	GTTGCAGGTCTCTAGTTTATGCTGTATGGCCTGCAAGATGATCTTTACAGATACTGTGATACGGATC
	AGAAACCGACACAATGATGTCATTCCCACAATGGCCCAGGGTGTGATTGAATACAAGGACAGCTTTG
	GGGTGGATCCTGTCACCAGCCAGAATGTTCAGTACTTTATTTATCGTTTTCACAAAACTATTTGAGT
	AGAATAAATGGAAACTGAATTCCATTTGTGCCCGTTAAACCTCCTAAAGGATGAAATTGCACCTATT
	TTACACCTATATTTTCACAGTTAATTGAACATATTTTTAAACAACTGTAGTTTTGGGCAACTTTTCA
	CTTTGTGGTAGACTTCAGAAGPGTGGAAATCTTCGGGTTTCTATAGGAAACTAGTTTTTTTTTTTTT
	AAAAAAATCCTTTCTTTTTTGTGGGCTAG
	ORF Start: ATG at 109		ORF Stop: TGA at 733
	SEQ ID NO: 244	208 aa	MW at 23483.8 kD
NOV54c,	MRLARLLRGAALAGPGPGLRAAGFSRSFSSDSGSSPASERGVPGQVDFYARFSPSPLSMKQFLDFGS
CG96613-02
Protein Sequence	VNACEKTSFMFLRQELPVRLANIMKEISLLPDNLLRTPSVQLVQSWYIQSLQELLDFKDKSAEDAKA
	IYERPRRTWLQVSSLCCMACKMIFTDTVIRTRNRHNDVIPTMAQGVIEYKESFGVDPVTSQNVQYFI
	YRFHKTI

[0632] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 54B.

TABLE 54B
Comparison of NOV54a against NOV54b and NOV54c.
			Identities/
			Similarities
	Protein	NOV54a Residues/	for the
	Sequence	Match Residues	Matched Region
	NOV54b	42 . . . 436	394/415 (94%)
		42 . . . 456	395/415 (94%)
	NOV54c	42 . . . 185	140/164 (85%)
		42 . . . 205	143/164 (86%)

[0633] Further analysis of the NOV54a protein yielded the following properties shown in Table 54C.

TABLE 54C
Protein Sequence Properties NOV54a
PSort     0.4251 probability located in mitochondrial
analysis: matrix space; 0.3802 probability
          located in microbody (peroxisome); 0.1914
          probability located in lysosome
          (lumen); 0.1017 probability located in
          mitochondrial inner membrane
SignalP   Cleavage site between residues 22 and 23
analysis:

[0634] A search of the NOV54a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 54D.

TABLE 54D
Geneseq Results for NOV54a
		NOV54a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
ABG16621	Novel human diagnostic	42 . . . 435	269/395 (68%)	e−162
	protein #16612 - Homo	21 . . . 413	331/395 (83%)
	sapiens, 415 aa.
	[WO200175067-A2,
	11 OCT. 2001]
ABB58044	Drosophila melanogaster	26 . . . 420	219/401 (54%)	e−121
	polypeptide SEQ ID NO 924 -	2 . . . 396	288/401 (71%)
	Drosophila melanogaster,
	413 aa. [WO200171042-A2,
	27 SEP. 2001]
AAE07838	Maize pyruvate	40 . . . 401	144/374 (38%)	2e−60
	dehydrogenase kinase	8 . . . 364	211/374 (55%)
	(PDK)-2 - Zea mays, 364 aa.
	[US6265636-B1,
	24 JUL. 2001]
AAW64724	A. thaliana PDHK protein	57 . . . 401	142/357 (39%)	3e−58
	from clone YA5 -	29 . . . 366	209/357 (57%)
	Arabidopsis thaliana, 366 aa.
	[WO9835044-A1,
	13 AUG. 1998]
AAE07837	Maize pyruvate	40 . . . 401	135/371 (36%)	4e−56
	dehydrogenase kinase	8 . . . 347	205/371 (54%)
	(PDK)-1 - Zea mays, 347 aa.
	[US6265636-B1,
	24 JUL. 2001]

[0635] In a BLAST search of public sequence datbases, the NOV54a protein was found to have homology to the proteins shown in the BLASTP data in Table 54E.

TABLE 54E
Public BLASTP Results for NOV54a
		NOV54a	Identities/
Protein		Residues/	Similarities
Accession		Match	for the
Number	Protein/Organism/Length	Residues	Matched Portion	Expect Value
Q15118	[Pyruvate dehydrogenase	1 . . . 436	436/436 (100%)	0.0
	[lipoamide]] kinase isozyme	1 . . . 436	436/436 (100%)
	1, mitochondrial precursor
	(EC 2.7.1.99) (Pyruvate
	dehydrogenase kinase isoform
	1) - Homo sapiens (Human),
	436 aa.
Q63065	[Pyruvate dehydrogenase	1 . . . 436	402/436 (92%)	0.0
	[lipoamide]] kinase isozyme	1 . . . 434	412/436 (94%)
	1, mitochondrial precursor
	(EC 2.7.1.99) (Pyruvate
	dehydrogenase kinase isoform
	1) (PDK P48) - Rattus
	norvegicus (Rat), 434 aa.
Q8R2U8	Similar to pyruvate	1 . . . 436	401/436 (91%)	0.0
	dehydrogenase kinase,	1 . . . 432	412/436 (93%)
	isoenzyme 1 - Mus musculus
	(Mouse), 432 aa.
Q15119	[Pyruvate dehydrogenase	37 . . . 434	277/398 (69%)	e−168
	[lipoamide]] kinase isozyme	11 . . . 405	340/398 (84%)
	2, mitochondrial precursor
	(EC 2.7.1.99) (Pyruvate
	dehydrogenase kinase isoform
	2) - Homo sapiens (Human),
	407 aa.
I70159	[pyruvate dehydrogenase	37 . . . 434	276/398 (69%)	e−168
	(lipoamide)] kinase (EC	11 . . . 405	340/398 (85%)
	2.7.1.99) 2 - human, 407 aa.

[0636] PFam analysis predicts that the NOV54a protein contains the domains shown in the Table 54F.

TABLE 54F
Domain Analysis of NOV54a
		Identities/
		Similarities
Pfam	NOV54a Match	for the	Expect
Domain	Region	Matched Region	Value
HATPase_c	268 . . . 393	32/134 (24%)	8.5e−20
		84/134 (63%)

Example 55

[0637] The NOV55 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 55A.

TABLE 55A
NOV55 Sequence Analysis
	SEQ ID NO: 245	2885 bp
NOV55a,	CGGCACGCCCGGGACGCTTTCTCTGGCTGGTAACCGCTACTCCCGGACACCAGACCACCGCCTTCCG
CG96736-01
DNA Sequence	TACACAGGGGCCCGCATCCCACCCTCCCGGACCTAAGAGCCTGGGTCCCCTGTTTCCGGAGTCCGCT
	TCCCGGCCCCCAGATTCTCGCATCCCAGCCCTCAGTGTCCAAGACCCAGGCAGCCCGGGTCCCCCCC
	TCCCGGATCCACGCGTCCGGGATCTGCGCCACCAGAACCTAGCCTCCTGCAGACCTCCGCCATCTGG
	GGGCACTCAACCTCCTGGAGCCAACGGCCCCACGTCCCACCCAGAGAAACTCTCGTATTCCCAGCTC
	CTAGGGCCAAGACCCGCGCGCTCCGAACTCCCAGCTTTCGGACATCTGAAACACACGGGGCAGAGCA
	GAGAAGCCTCAGCGCCCAGCCTGGGGAATTTAAACACTCCAGCTTCCAAGAGCCAAGGAACTTCAGT
	GCTGTGAACTCACAACTCTAACCAGCCCTCCAAAGTTCCAGTCTCCAGGTGCTGTTACTCAACTCAG
	TCCTAGGAACGTCGGGTCCTGCGAAGGAGCCCAGCGCTCCCAAGCCAGCTTCCAGGCGCTAAGAAAC
	CCCGGTGCTTCCCATCATGGTGGCCGATCCTCCTCGAGACTCCAAGGGGCTCGCAGCGGCGGAGCCA
	CCCCCAACGGGGGCCTGGCAGCTGGCCTCCATCGAGGACCAAGGCGCGGCAGCAGGCGGCTACTGCG
	GTTCCCGGGACCTGCTCCGCCGCTGCCTTCGAGCCAACCTGCTTGTGCTGCTGACAGTGGTCGCCGT
	GGTCGCCGGCGTGGCGCTGGGACTGGGGGTGTCGGGGGCCGCGCGTGCGCTGGCGTTGGGCCCGGGA
	GCGCTTGAGGCCTTCGTCTTCCCGCGCGAGCTGCTGCTGCGTCTGCTGCGGATGATCATCTTGCCGC
	TGGTGGTGTGCAGCTTGATCGGCGGCGCCGCCAGCCTCGACCCCGGCGCGCTCGGCCGTCTGGCCCC
	CTGGGCGCTGCTCTTTTTCCTGGTCACCACGCTGCTGGCGTCGGCGCTCGGAGTGGGCTTGGCGCTG
	GCTCTGCAGCCGGGCGCCGCCTCCGCCGCCATCAACGCCTCCGTGGGAGCCGCGGGCAGTGCCGAAA
	ATGCCCCCAGCAAGGAAGTGCTCGATTCGTTCCTGGATCTTGCGAGAAATATCTTCCCTTCCAACCT
	GGTGTCAGCAGCCTTTCGCTCATACTCTACCACCTATGAAGAGAGGAATATCACCGGAACCAGGGTG
	AAGGTGCCCGTGGGGCAGGAGGTGGAGGGGATGAACATCCTGGGCTTGGTAGTGTTTGCCATCGTCT
	TTGGTGTGGCGCTGCGGAAGCTGGGGCCTGAGGGGAGCTGCTTAATCCGCTTCTTCAACTCCTTCAA
	TGAGGCCACCATGGTTCTGGTCTCCTCGATCATGTGGTACCCCCCTGTGGGCATCATGTTCCTGGTG
	GCTGGCAAGATCGTGGAGATGGAGGATGTGGGTTTACTCTTTGCCCGCCTTGGCAAATACATTCTGT
	GCTGCCTGCTGCGTCACGCCATCCATGGGCTCCTGGTACTGCCCCTCATCTACTTCCTCTTCACCCG
	CAAAAACCCCTACCGCTTCCTGTGGGGCATCGTGACGCCCCTGGCCACTGCCTTTGGGACCTCTTCC
	AGTTCCGCCACGCTGCCGCTGATGATGAAGTGCGTGGAGGAGAATAATGGCGTGGCCAAGCACATCA
	GCCGTTTCATCCTGCCCATCGGCGCCACCGTCAACATGGACGGTGCCGCGCTCTTCCAGTGCGTGGC
	CGCAGTGTTCATTGCACAGCTCAGCCAGCAGTCCTTGGACTTCCTAAAGATCATCACCATCCTGGTC
	ACGGCCACAGCGTCCAGCGTGGGGGCAGCGGGCATCCCTGCTGGAGGTGTCCTCACTCTGGCCATCA
	TCCTCGAAGCAGTCAACCTCCCGGTCGACCATATCTCCTTGATCCTGGCTGTGGACTGGCTAGTCGA
	CCGGTCCTGTACCGTCCTCAATGTAGAAGGTGACGCTCTGGGGGCAGGACTCCTCCAAAATTATGTG
	GACCGTACGGAGTCGAGAAGCACAGAGCCTGAGTTGATACAAGTGAAGAGTGAGCTGCCCCTGGATC
	CGCTGCCAGTCCCCACTGAGGAAGGAAACCCCCTCCTCAAACACTATCGGGGGCCCGCAGGGGATGC
	CACGGTCGCCTCTGAGAAGGAATCAGTCATGTAAACCCCGGGAGGGACCTTCCCTGCCCTGCTGGGG
	GTGCTCTTTGGACACTGGATTATGAGGAATGGATAAATGGATGAGCTAGGGCTCTGGGGGTCTGCCT
	GCACACTCTGGGGAGCCAGGGGCCCCAGCACCCTCCACGACAGGAGATCTGGGATGCCTGGCTGCTG
	GAGTACATGTGTTCACAAGGGTTACTCCTCAAAACCCCCAGTTCTCACTCATGTCCCCAACTCAAGG
	CTAGAAAACAGCAACATGGACAAATAATGTTCTGCTGCGTCCCCACCGTGACCTGCCTGGCCTCCCC
	TGTCTCAGGGAGCAGGTCACAGGTCACCATGGGGAATTCTAGCCCCCACTGGGGGGATGTTACAACA
	CCATGCTGGTTATTTTGGCGGCTGTAGTTGTGGCGGGATGTGTGTGTGCACGTGTGTGTGTGTGTGT
	GTGTGTGTGTGTGTGTGTGTTCTGTGACCTCCTGTCCCCATCGTACGTCCCACCCTGTCCCCAGATC
	CCCTATTCCCTCCACAATAACAGAAACACTCCCAGGGACTCTGGGGAGAGGCTGACCACAAATACCT
	GCTGTCACTCCAGAGGACATTTTTTTTAGCAATAAAATTGAGTGTCAACTATTAAAAAAAAAAAAAA
	AAAA
	ORF Start: ATG at 620		ORF Stop: TAA at 2243
	SEQ ID NO: 246	541 aa	MW at 56620.6 kD
NOV55a,	MVADPPRDSKGLAAAEPPPTGAWQLASIEDQGAAAGGYCGSRDLVRRCLRANLLVLLTVVAVVAGVA
CG96736-01
Protein Sequence	LGLGVSCACGALALGPGALEAFVFPGELLLRLLRNIILPLVVCSLIGGAASLDPGALGRLGAWALLF
	FLVTTLLASALGVGLALALQPGAASAAINASVCAAGSAENAPSKEVLDSFLDLARNIFPSNLVSAAF
	RSYSTTYEERNITGTRVXVPVGQEVEGMNILGLVVFAIVFGVALRKLGPEGELLIRFFNSFNEATMV
	LVSWTMWYAPVGIMFLVAGKIVEMEDVGLLFARLGKYILCCLLGHAIHGLLVLPLIYFLFTRKNPYR
	FLWGIVTPLATAFGTSSSSATLPLMMKCVEENNGVAKHISRFILPIGATVNMDGAALFQCVAAVFIA
	QLSQQSLDFVKIITILVTATASSVGAAGIPAGGVLTLAIILEAVNLPVDHISLILAVDWLVDRSCTV
	LNVEGDALGAGLLQNYVDRTESRSTEPELIQVKSELPLDPLPVPTEEGNPLLKHYRGPAGDATVASE
	SEQ ID NO: 247	2017 bp
NOV55b,	CGTACAACTCCGCCCCATTGACGCAAATGGGCGGTAGGCGTGTACGGTGGGAGGTCTATATAAGCAG
CG96736-02
DNA Sequence	AGCTCTCTGGCTAACTAGAGAACCCACTGCTTACTGGCTTATCGAAATTAATACGACTCACTATAGG
	GAGACCCAAGCTGGCTAGCGTTTAAACTTAAGCTTGGTACCGAGCTCGCATCCACTAGTCCAGTGTG
	GTGGAATTCCACCATGGTCGCCGATCCTCCTCGAGACTCCAAGGGCCTCGCAGCGGCGGACCCCACC
	GCCAACGGGGGCCTGGCGCTGGCCTCCATCGAGGACCAAGGCGCGGCAGCAGCCGGCTACTGCGGTT
	CCCCGGACCAGGTGCGCCGCTGCCTTCGAGCCAACCTCCTTGTGCTGCTGACAGTGGTGGCCCTGGT
	GGCCGGCGTCGCGCTGGGACTGGGGGTGTCGGGGGCCGGGGGTGCGCTGGCGTTGGGCCCGGAGCGC
	TTGAGCGCCTTCGTCTTCCCGGGCGAGCTGCTGCTGCGTCTGCTGCGGATGATCATCTTGCCGCTGG
	TGGTGTGCAGCTTGATCGGCGGCGCCGCCAGCCTGGACCCCGGCGCGCTCGGCCGTCTGAACGCCTG
	GGCGCTGCTCTTTTTCCTGGTCACCACGCTGCTGGCGTCGGCGCTCGGAGTAAGCTTGGCGCTGGCT
	CTGCAGCCGGGCGCCGCCTCCGCCGCCATCAACGCCTCCGTGGGAGCCGCGGGCAGTGCCGAAAATG
	CCCCCAGCAAGGAGGTGCTCGATTCGTTCCTGGATCTTGCGAGAAATATCTTCCCTTCCAACCTAAT
	GTCAGCAGCCTTTCGCTCATACTCTACCACCTATGAAGAGAGGAATATCACCGGAACCAGGGTGAAG
	GTGCCCGTGGGGCAGGAGGTGGAGGGGATGAACATCCTGGGCTTGGTAGTGTTTGCCATCGTCTTTG
	GTGTGGCGCTGCCGAAGCTGGGGCCTGAAGGGGAGCTGCTTATCCGCTTCTTCAACTCCTTCAATGA
	GGCCACCATGGTTCTGGTCTCCTGGATCATGTGGTATGCCCCTGTGGGCATCATGTTCCTCGTGGCT
	GGCAAGATCGTGGAGATGGAGGATGTGGGTTTACTCTTTGCCCGCCTTGGCAAGTACATTCTGTGCT
	GCCTGCTGGGTCACGCCATCCATGGGCTCCTGGTACTGCCCCTCATCTACTTCCTCTTCACCCGCAA
	AAACCCCTACCGCTTCCTGTGGGGCATCGTGACGCCGCTGGCCACTGCCTTTGGGACCTCTTCCAGT
	TCCGCCACGCTGCCGCTGATGATGAAGTGCGTGGAGGAGAATAATGGCGTGGCCAAGCACATCAGCC
	GTTTCATCCTGCCCATCGGCGCCACCGTCAACATGGACGGTGCCGCGCTCTTCCAGTGCGTGGCCGC
	AGTGTTCATTGCACAGCTCAGCCAGCAGTCCTTGGACTTCGTAAAGATCATCACCATCCTGGTCACG
	GCCACAGCGTCCAGCGTGGGGGCAGCGGGCATCCCTGCTGGAGGTGTCCTCACTCTGGCCATCATCC
	TCCAAGCAGTCAACCTCCCGGTCGACCATATCTCCTTGATCCTGGCTGTGGACTGGCTAGTCGACCG
	GTCCTGTACCGTCCTCAATGTAGAAGGTGACGCTCTGGGGGCAGGACTCCTCCAAAATTACGTGGAC
	CGTACGGAGTCGAGAAGCACAGAGCCTGAGTTGATACAAGTGAAGAGTGAGCTGCCCCTGGATCCGC
	TGCCAGTCCCCACTGAGGAAGGAAACCCCCTCCPCAAACACTATCGGGGGCCCGCAGGGGATGCCAC
	GGTCGCCTCTGAGAAGGAATCAGTCATGTAAGCGGCCGCTCGAGTCTAGAGGGCCCGTTTAAACCCG
	CTGATCAGCCTCGACTGTGCCTTCTAGTTGCCAGCCATCTGTTGTTTGCCCCTCCCCCGTGCCTTCC
	TTGACCCTGGAAGGTGCCACTCCCACTGTCCTTTCCTAATAAAATGAGGAAATTGCATCGCATTGTC
	TGAGTAG
	ORF Start: at 134		ORF Stop: TAA at 1838
	SEQ ID NO: 248	568 aa	MW at 59557.8 kD
NOV55b,	GDPSWLAFKLKLGTELGSTSPVWWNSTMVADPPRDSKCLAAAEPTANGGLALASIEDQGAAAGGYCG
CG96736-02
Protein Sequence	SRDQVRRCLRANLLVLLTVVAVVAGVALGLGVSGAGGALALGPERLSAFVFPGELLLRLLRMIILPL
	VVCSLIGGAASLDPGALGRLGAWALLFFLVTTLLASALGVGLALALQPGAASAAINASVGAAGSAEN
	APSKEVLDSFLDLARNIFPSNLVSAAFRSYSTTYEERNITGTRVKVPVGQEVEGNNILGLVVFAIVF
	GVALRKLGPEGELLIRFFNSFNEATMVLVSWIMWYAPVGIMFLVAGKIVEMEDVGLLFARLGKYILC
	CLLGHAIHGLLVLPLIYFLFTRKNPYRFLWGTVTPLATAFGTSSSSATLPLMMKCVEENNGVAKHIS
	RFILPIGATVNMDGAALFQCVAAVFIAQLSQQSLDFVKIITILVTATASSVGAAGIPAGGVLTLAII
	LEAVNLPVDHISLILAVDWLVDRSCTVLNVEGDALCAGLLQNYVDRTESRSTEPELIQVKSELPLDP
	LPVPTEEGNPLLKHYRGPAGDATVASEKESVM

[0638] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 55B.

TABLE 55B
Comparison of NOV55a against NOV55b.
			Identities/
			Similarities
	Protein	NOV55a Residues/	for the
	Sequence	Match Residues	Matched Region
	NOV55b	1 . . . 541	423/541 (78%)
		28 . . . 568	423/541 (78%)

[0639] Further analysis of the NOV55a protein yielded the following properties shown in Table 55C.

TABLE 55C
Protein Sequence Properties NOV55a
PSort     0.6000 probability located in plasma
analysis: membrane; 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 70 and 71
analysis:

[0640] A search of the NOV55a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 55D.

TABLE 55D
Geneseq Results for NOV55a
		NOV55a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched
Identifier	[Patent #, Date]	Residues	Region	Expect Value
ABG61858	Prostate cancer-associated	1 . . . 541	531/541 (98%)	0.0
	protein #59 - Mammalia, 541	1 . . . 541	531/541 (98%)
	aa. [WO200230268-A2,
	18 APR. 2002]
AAR95044	Apoptosis participating	1 . . . 513	499/513 (97%)	0.0
	protein - Homo sapiens, 514	1 . . . 513	499/513 (97%)
	aa. [JP08089257-A,
	09 APR. 1996]
AAY78144	Human neutral amino acid	32 . . . 541	314/521 (60%)	e−161
	transporter ASCT1 - Homo	21 . . . 532	378/521 (72%)
	sapiens, 532 aa.
	[US6020479-A,
	01 FEB. 2000]
AAY99961	Human amino acid	32 . . . 541	314/521 (60%)	e−161
	transporter ASCT1 protein -	21 . . . 532	378/521 (72%)
	Homo sapiens, 532 aa.
	[US6074828-A,
	13 JUN. 2000]
AAY97139	ASCT1 human neutral amino	32 . . . 541	314/521 (60%)	e−161
	acid transporter protein -	21 . . . 532	378/521 (72%)
	Homo sapiens, 532 aa.
	[US6100085-A,
	08 AUG. 2000]

[0641] In a BLAST search of public sequence datbases, the NOV55a protein was found to have homology to the proteins shown in the BLASTP data in Table 55E.

TABLE 55E
Public BLASTP Results for NOV55a
		NOV55a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched
Number	Protein/Organism/Length	Residues	Portion	Expect Value
AAD09814	Neutral amino acid	1 . . . 541	532/541 (98%)	0.0
	transporter - Homo sapiens	1 . . . 541	532/541 (98%)
	(Human), 541 aa.
Q15758	Neutral amino acid	1 . . . 541	531/541 (98%)	0.0
	transporter B(0) (ATB(0))	1 . . . 541	531/541 (98%)
	(Sodium-dependent neutral
	amino acid transporter type
	2) (RD114/simian type D
	retrovirus receptor) (Baboon
	M7 virus receptor) - Homo
	sapiens (Human), 541 aa.
O19105	Neutral amino acid	1 . . . 541	459/542 (84%)	0.0
	transporter B(0) (ATB(0))	1 . . . 541	485/542 (88%)
	(Sodium-dependent neutral
	amino acid transporter type
	2) - Oryctolagus cuniculus
	(Rabbit), 541 aa.
Q95JC7	Neutral amino acid	1 . . . 541	465/542 (85%)	0.0
	transporter B(0) (ATB(0))	1 . . . 539	486/542 (88%)
	(Sodium-dependent neutral
	amino acid transporter type
	2) - Bos taurus (Bovine), 539
	aa.
AAM94351	Na+-dependent amino acid	1 . . . 541	445/553 (80%)	0.0
	transporter ASCT2 - Rattus	1 . . . 551	471/553 (84%)
	norvegicus (Rat), 551 aa.

[0642] PFam analysis predicts that the NOV55a protein contains the domains shown in the Table 55F.

TABLE 55F
Domain Analysis of NOV55a
			Identities/
			Similarities
	Pfam	NOV55a Match	for the	Expect
	Domain	Region	Matched Region	Value
	SDF	54 . . . 485	195/465 (42%)	1.5e−178
			373/465 (80%)

Example B: Sequencing Methodology and Identification of NOVX Clones

[0643] 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.

[0644] 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.

[0645] 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.

[0646] The laboratory screening was performed using the methods summarized below:

[0647] 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).

[0648] 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.

[0649] 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).

[0650] 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.

[0651] 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.

[0652] 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.

[0653] The PCR product derived by exon linking, covering the entire open reading frame, was cloned into the pCR2.1 vector from Invitrogen to provide clones used for expression and screening purposes.

Example C: Quantitative Expression Analysis of Clones in Various Cells and Tissues

[0654] 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_pancl (containing normal tissue and samples from autoinflammatory diseases), Panel CNSD.01 (containing samples from normal and diseased brains) and CNS_neurodegeneration_panel (containing samples from normal and Alzheimer's diseased brains).

[0655] 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.

[0656] 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.

[0657] 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.

[0658] 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.

[0659] PCR conditions: When working with RNA samples, normalized RNA from each tissue and each cell line was spotted in each well of either a 96 well or a 384-well PCR plate (Applied Biosystems). PCR cocktails included either a single gene specific probe and primers set, or two multiplexed probe and primers sets (a set specific for the target clone and another gene-specific set multiplexed with the target probe). PCR reactions were set up using TaqMan® One-Step RT-PCR Master Mix (Applied Biosystems, Catalog No. 4313803) following manufacturer's instructions. Reverse transcription was performed at 48° C. for 30 minutes followed by amplification/PCR cycles as follows: 95° C. 10 min, then 40 cycles of 95° C. for 15 seconds, 60° C. for 1 minute. Results were recorded as CT values (cycle at which a given sample crosses a threshold level of fluorescence) using a log scale, with the difference in RNA concentration between a given sample and the sample with the lowest CT value being represented as 2 to the power of delta CT. The percent relative expression is then obtained by taking the reciprocal of this RNA difference and multiplying by 100.

[0660] 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.

[0661] Panels 1, 1.1, 1.2, and 1.3D

[0662] 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.

[0663] In the results for Panels 1, 1.1, 1.2 and 1.3D, the following abbreviations are used:

[0664] ca.=carcinoma,

[0665] *=established from metastasis,

[0666] met=metastasis,

[0667] s cell var=small cell variant,

[0668] non-s=non-sm=non-small,

[0669] squam=squamous,

[0670] pl. eff=p1 effusion=pleural effusion,

[0671] glio=glioma,

[0672] astro=astrocytoma, and

[0673] neuro=neuroblastoma.

[0674] General_screening_panel_v1.4, v1.5 and v1.6

[0675] The plates for Panels 1.4, 1.5, and 1.6 include 2 control wells (genomic DNA control and chemistry control) and 94 wells containing cDNA from various samples. The samples in Panels 1.4, 1.5, and 1.6 are broken into 2 classes: samples derived from cultured cell lines and samples derived from primary normal tissues. The cell lines are derived from cancers of the following types: lung cancer, breast cancer, melanoma, colon cancer, prostate cancer, CNS cancer, squamous cell carcinoma, ovarian cancer, liver cancer, renal cancer, gastric cancer and pancreatic cancer. Cell lines used in Panels 1.4, 1.5, and 1.6 are widely available through the American Type Culture Collection (ATCC), a repository for cultured cell lines, and were cultured using the conditions recommended by the ATCC. The normal tissues found on Panels 1.4, 1.5, and 1.6 are comprised of pools of samples derived from all major organ systems from 2 to 5 different adult individuals or fetuses. These samples are derived from the following organs: adult skeletal muscle, fetal skeletal muscle, adult heart, fetal heart, adult kidney, fetal kidney, adult liver, fetal liver, adult lung, fetal lung, various regions of the brain, the spleen, bone marrow, lymph node, pancreas, salivary gland, pituitary gland, adrenal gland, spinal cord, thymus, stomach, small intestine, colon, bladder, trachea, breast, ovary, uterus, placenta, prostate, testis and adipose. Abbreviations are as described for Panels 1, 1.1, 1.2, and 1.3D.

[0676] Panels 2D, 2.2, 2.3 and 2.4

[0677] The plates for Panels 2D, 2.2, 2.3 and 2.4 generally include 2 control wells and 94 test samples composed of RNA or cDNA isolated from human tissue procured by surgeons working in close cooperation with the National Cancer Institute's Cooperative Human Tissue Network (CHTN) or the National Disease Research Initiative (NDRI) or from Ardais or Clinomics). The tissues are derived from human malignancies and in cases where indicated many malignant tissues have “matched margins” obtained from noncancerous tissue just adjacent to the tumor. These are termed normal adjacent tissues and are denoted “NAT” in the results below. The tumor tissue and the “matched margins” are evaluated by two independent pathologists (the surgical pathologists and again by a pathologist at NDRI/CHTN/Ardais/Clinomics). Unmatched RNA samples from tissues without malignancy (normal tissues) were also obtained from Ardais or Clinomics. This analysis provides a gross histopathological assessment of tumor differentiation grade. Moreover, most samples include the original surgical pathology report that provides information regarding the clinical stage of the patient. These matched margins are taken from the tissue surrounding (i.e. immediately proximal) to the zone of surgery (designated “NAT”, for normal adjacent tissue, in Table RR). In addition, RNA and cDNA samples were obtained from various human tissues derived from autopsies performed on elderly people or sudden death victims (accidents, etc.). These tissues were ascertained to be free of disease and were purchased from various commercial sources such as Clontech (Palo Alto, CA), Research Genetics, and Invitrogen.

[0678] HASS Panel v 1.0

[0679] 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.

[0680] ARDAIS Panel v 1.0

[0681] 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.

[0682] Panel 3D, 3.1 and 3.2

[0683] The plates of Panel 3D, 3.1, and 3.2 are comprised of 94 cDNA samples and two control samples. Specifically, 92 of these samples are derived from cultured human cancer cell lines, 2 samples of human primary cerebellar tissue and 2 controls. The human cell lines are generally obtained from ATCC (American Type Culture Collection), NCI or the German tumor cell bank and fall into the following tissue groups: Squamous cell carcinoma of the tongue, breast cancer, prostate cancer, melanoma, epidermoid carcinoma, sarcomas, bladder carcinomas, pancreatic cancers, kidney cancers, leukemias/lymphomas, ovarian/uterine/cervical, gastric, colon, lung and CNS cancer cell lines. In addition, there are two independent samples of cerebellum. These cells are all cultured under standard recommended conditions and RNA extracted using the standard procedures. The cell lines in panel 3D, 3.1, 3.2, 1, 1.1., 1.2, 1.3D, 1.4, 1.5, and 1.6 are of the most common cell lines used in the scientific literature.

[0684] Panels 4D, 4R, and 4.1D 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.).

[0685] Astrocytes, lung fibroblasts, dermal fibroblasts, coronary artery smooth muscle cells, small airway epithelium, bronchial epithelium, microvascular dermal endothelial cells, microvascular lung endothelial cells, human pulmonary aortic endothelial cells, human umbilical vein endothelial cells were all purchased from Clonetics (Walkersville, MD) and grown in the media supplied for these cell types by Clonetics. These primary cell types were activated with various cytokines or combinations of cytokines for 6 and/or 12-14 hours, as indicated. The following cytokines were used; IL-1 beta at approximately 1-5 ng/ml, TNF alpha at approximately 5-10 ng/ml, IFN gamma at approximately 20-50 ng/ml, IL-4 at approximately 5-10 ng/ml, IL-9 at approximately 5-10 ng/ml, IL-13 at approximately 5-10 ng/ml. Endothelial cells were sometimes starved for various times by culture in the basal media from Clonetics with 0.1% serum.

[0686] Mononuclear cells were prepared from blood of employees at CuraGen Corporation, using Ficoll. LAK cells were prepared from these cells by culture in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco/Life Technologies, Rockville, Md.), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), and 10 mM Hepes (Gibco) and Interleukin 2 for 4-6 days. Cells were then either activated with 10-20 ng/ml PMA and 1-2 μg/ml ionomycin, IL-12 at 5-10 ng/ml, IFN gamma at 20-50 μg/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 5.5×10−5 M (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 2×106cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol (5.5×10−5M) (Gibco), and 10 mM Hepes (Gibco). The MLR was cultured and samples taken at various time points ranging from 1-7 days for RNA preparation.

[0687] Monocytes were isolated from mononuclear cells using CD14 Miltenyi Beads, +ve VS selection columns and a Vario Magnet according to the manufacturer's instructions. Monocytes were differentiated into dendritic cells by culture in DMEM 5% fetal calf serum (FCS) (Hyclone, Logan, Utah), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), and OnmM 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.

[0688] CD4 lymphocytes, CD8 lymphocytes and NK cells were also isolated from mononuclear cells using CD4, CD8 and CD56 Miltenyi beads, positive VS selection columns and a Vario Magnet according to the manufacturer's instructions. CD45RA and CD45RO CD4 lymphocytes were isolated by depleting mononuclear cells of CD8, CD56, CD14 and CD19 cells using CD8, CD56, CD14 and CD19 Miltenyi beads and positive selection. CD45RO beads were then used to isolate the CD45RO CD4 lymphocytes with the remaining cells being CD45RA CD4 lymphocytes. CD45RA CD4, CD45RO CD4 and CD8 lymphocytes were placed in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), and 10 mM Hepes (Gibco) and plated at 106 cells/ml onto Falcon 6 well tissue culture plates that had been coated overnight with 0.5 μg/ml anti-CD28 (Pharmingen) and 3 ug/ml anti-CD3 (OKT3, ATCC) in PBS. After 6 and 24 hours, the cells were harvested for RNA preparation. To prepare chronically activated CD8 lymphocytes, we activated the isolated CD8 lymphocytes for 4 days on anti-CD28 and anti-CD3 coated plates and then harvested the cells and expanded them in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), and 10 mM Hepes (Gibco) and IL-2. The expanded CD8 cells were then activated again with plate bound anti-CD3 and anti-CD28 for 4 days and expanded as before. RNA was isolated 6 and 24 hours after the second activation and after 4 days of the second expansion culture. The isolated NK cells were cultured in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), and 10 mM Hepes (Gibco) and IL-2 for 4-6 days before RNA was prepared.

[0689] To obtain B cells, tonsils were procured from NDRI. The tonsil was cut up with sterile dissecting scissors and then passed through a sieve. Tonsil cells were then spun down and resupended at 106 cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5 M (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.

[0690] 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 21 μg/ml OKT3 (ATCC), and then washed twice with PBS. Umbilical cord blood CD4 lymphocytes (Poietic Systems, German Town, Md.) were cultured at 105-106 cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), 10 mM Hepes (Gibco) and IL-2 (4 ng/ml). IL-12 (5 ng/ml) and anti-IL4 (1 μg/ml) were used to direct to Th1, while IL-4 (5 ng/ml) and anti-IFN gamma (1 μg/ml) were used to direct to Th2 and IL-10 at 5 ng/ml was used to direct to Tr1. After 4-5 days, the activated Th1, Th2 and Tr1 lymphocytes were washed once in DMEM and expanded for 4-7 days in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), 10 mM Hepes (Gibco) and IL-2 (1 ng/ml). Following this, the activated Th1, Th2 and Tr1 lymphocytes were re-stimulated for 5 days with anti-CD28/OKT3 and cytokines as described above, but with the addition of anti-CD95L (1 ng/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.

[0691] 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). CCD1106 cells were activated for 6 and 14 hours with approximately 5 ng/ml TNF alpha and 1 ng/ml IL-1 beta, while NCI-H292 cells were activated for 6 and 14 hours with the following cytokines: 5 ng/ml IL-4, 5 ng/ml IL-9, 5 ng/ml IL-13 and 25 ng/ml IFN gamma.

[0692] For these cell lines and blood cells, RNA was prepared by lysing approximately 107 cells/ml using Trizol (Gibco BRL). Briefly, 1/10 volume of bromochloropropane (Molecular Research Corporation) was added to the RNA sample, vortexed and after 10 minutes at room temperature, the tubes were spun at 14,000 rpm in a Sorvall SS34 rotor. The aqueous phase was removed and placed in a 15 ml Falcon Tube. An equal volume of isopropanol was added and left at −20° C. overnight. The precipitated RNA was spun down at 9,000 rpm for 15 min in a Sorvall SS34 rotor and washed in 70% ethanol. The pellet was redissolved in 300 μl of RNAse-free water and 35 μl buffer (Promega) 5 μl DTT, 7 μl RNAsin and 8 μl DNAse were added. The tube was incubated at 37° C. for 30 minutes to remove contaminating genomic DNA, extracted once with phenol chloroform and re-precipitated with 1/10 volume of 3M sodium acetate and 2 volumes of 100% ethanol. The RNA was spun down and placed in RNAse free water. RNA was stored at −80° C.

[0693] Al_comprehensive panel_v1.0

[0694] The plates for Alcomprehensive 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.

[0695] 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.

[0696] 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.

[0697] 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.

[0698] 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.

[0699] In the labels employed to identify tissues in the AI_comprehensive panel_v 1.0 panel, the following abbreviations are used:

[0700] AI=Autoimmunity

[0701] Syn=Synovial

[0702] Normal=No apparent disease

[0703] Rep22/Rep20=individual patients

[0704] RA=Rheumatoid arthritis

[0705] Backus=From Backus Hospital

[0706] OA=Osteoarthritis

[0707] (SS)(BA) (MF)=Individual patients

[0708] Adj=Adjacent tissue

[0709] Match control=adjacent tissues

[0710] -M=Male

[0711] -F=Female

[0712] COPD=Chronic obstructive pulmonary disease

[0713] AI.05 chondrosarcoma

[0714] The AI.05 chondrosarcoma plates are comprised of SW1353 cells that had been subjected to serum starvation, and treatment with cytokines that are known to induce MMP (1, 3 and 13) synthesis (eg. IL1beta). These treatments include: IL-1β (10 ng/ml), IL-1β+TNF-α (50 ng/ml), IL-1β+Oncostatin (50 ng/ml) and PMA (100 ng/ml). The SW1353 cells were obtained from ATCC (American Type Culture Collection) and were all cultured under standard recommended conditions. The SW1353 cells were plated at 3×105 cells/ml (in DMEM medium-10% FBS) in 6-well plate. The treatment was done in triplicate, for 6 and 18 h. The supernatants were collected for analysis of MMP 1, 3 and 13 production and for RNA extraction. RNA was prepared from these samples using the standard procedures.

[0715] Panels 5D and 5I

[0716] The plates for Panel 5D and 5I include two control wells and a variety of cDNAs isolated from human tissues and cell lines with an emphasis on metabolic diseases. Metabolic tissues were obtained from patients enrolled in the Gestational Diabetes study. Cells were obtained during different stages in the differentiation of adipocytes from human mesenchymal stem cells. Human pancreatic islets were alsoh obtained.

[0717] 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:

[0718] Patient 2: Diabetic Hispanic, overweight, not on insulin

[0719] Patient 7-9: Nondiabetic Caucasian and obese (BMI>30)

[0720] Patient 10: Diabetic Hispanic, overweight, on insulin

[0721] Patient 11: Nondiabetic African American and overweight

[0722] Patient 12: Diabetic Hispanic on insulin

[0723] Adiocyte differentiation was induced in donor progenitor cells obtained from Osirus (a division of Clonetics/BioWhittaker) in triplicate, except for Donor 3U which had only two replicates. Scientists at Clonetics isolated, grew and differentiated human mesenchymal stem cells (HuMSCs) for CuraGen based on the published protocol found in Mark F. Pittenger, et al., Multilineage Potential of Adult Human Mesenchymal Stem Cells Science Apr. 2 1999: 143-147. Clonetics provided Trizol lysates or frozen pellets suitable for mRNA isolation and ds cDNA production. A general description of each donor is as follows:

[0724] Donor 2 and 3 U: Mesenchymal Stem cells, Undifferentiated Adipose

[0725] Donor 2 and 3 μM: Adipose, AdiposeMidway Differentiated

[0726] Donor 2 and 3 AD: Adipose, Adipose Differentiated

[0727] 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.

[0728] 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.

[0729] In the labels employed to identify tissues in the 5D and 5I panels, the following abbreviations are used:

[0730] GO Adipose=Greater Omentum Adipose

[0731] SK=Skeletal Muscle

[0732] UT=Uterus

[0733] PL=Placenta

[0734] AD=Adipose Differentiated

[0735] AM=Adipose Midway Differentiated

[0736] U=Undifferentiated Stem Cells

[0737] Panel CNSD.01

[0738] 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.

[0739] 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.

[0740] In the labels employed to identify tissues in the CNS panel, the following abbreviations are used:

[0741] PSP=Progressive supranuclear palsy

[0742] Sub Nigra=Substantia nigra

[0743] Glob Palladus=Globus palladus

[0744] Temp Pole=Temporal pole

[0745] Cing Gyr=Cingulate gyrus

[0746] BA 4=Brodman Area 4

[0747] Panel CNS_Neurodegeneration_V1.0

[0748] 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.

[0749] 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.

[0750] In the labels employed to identify tissues in the CNS_Neurodegeneration_V1.0 panel, the following abbreviations are used:

[0751] AD=Alzheimer's disease brain; patient was demented and showed AD-like pathology upon autopsy

[0752] Control=Control brains; patient not demented, showing no neuropathology

[0753] Control (Path)=Control brains; pateint not demented but showing sever AD-like pathology

[0754] SupTemporal Ctx=Superior Temporal Cortex

[0755] Inf Temporal Ctx=Inferior Temporal Cortex

[0756] A. CG106764-01: RHO/RAC-INTERACTING CITRON KINASE.

[0757] Expression of gene CG106764-01 was assessed using the primer-probe set Ag2100, described in Table AA. Results of the RTQ-PCR runs are shown in Tables AB, AC, AD, AE, AF, AG, AH and AI.

TABLE AA
Probe Name AG2100
			Start	SEQ ID
Primers	Sequence	Length	Position	No
Forward	5′-agatccctggaacagaggatt-3′	21	2446	249
Probe	TET-5′-tgtctgaagccaataaacttgcagca-3′-TAMRA	26	2474	250
Reverse	5′-ccttcatgttcctttgggtaa-3′	121	2513	251

[0758]

TABLE AB
AI.05 chondrosarcoma
                                 Rel.
                                 Exp. (%)
                                 Ag2100,
                                 Run
Tissue Name                      306913849
138353_PMA (18 hrs)              9.3
138352_IL-1beta + Oncostatin M (18 hrs) 5.5
138351_IL-1beta + TNFa (18 hrs)  12.5
138350_IL-1beta (18 hrs)         12.5
138354_Untreated-complete medium (18 hrs) 13.2
138347_PMA (6 hrs)               34.9
138346_IL-1beta + Oncostatin M (6 hrs) 64.2
138345_IL-1beta + TNFa (6 hrs)   44.8
138344_IL-1beta (6 hrs)          25.5
138349_Untreated-serum starved (6 hrs) 100.0
138348_Untreated-complete medium (6 hrs) 41.2

[0759]

TABLE AC
AI_comprehensive panel_v1.0
	Rel.	Rel.
	Exp. (%)	Exp. (%)
	Ag2100,	Ag2100,
	Run	Run
Tissue Name	211059880	212328504
110967 COPD-F	0.5	0.8
110980 COPD-F	1.5	1.2
110968 COPD-M	0.4	0.6
110977 COPD-M	1.5	1.9
110989 Emphysema-F	4.2	6.0
110992 Emphysema-F	2.8	2.9
110993 Emphysema-F	0.9	0.8
110994 Emphysema-F	0.7	0.4
110995 Emphysema-F	2.0	5.4
110996 Emphysema-F	2.2	2.4
110997 Asthma-M	1.9	3.1
111001 Asthma-F	1.4	2.7
111002 Asthma-F	1.0	1.0
111003 Atopic Asthma-F	4.0	2.2
111004 Atopic Asthma-F	16.6	17.0
111005 Atopic Asthma-F	7.2	5.5
111006 Atopic Asthma-F	0.9	0.7
111417 Allergy-M	1.9	2.4
112347 Allergy-M	0.0	0.1
112349 Normal Lung-F	0.0	0.0
112357 Normal Lung-F	6.1	6.0
112354 Normal Lung-M	1.5	2.3
112374 Crohns-F	2.9	5.2
112389 Match Control Crohns-F	9.0	6.8
112375 Crohns-F	2.5	3.8
112732 Match Control Crohns-F	3.8	5.4
112725 Crohns-M	0.1	0.7
112387 Match Control Crohns-M	1.0	1.4
112378 Crohns-M	0.0	0.0
112390 Match Control Crohns-M	2.5	1.8
112726 Crohns-M	3.8	5.9
112731 Match Control Crohns-M	3.6	6.7
112380 Ulcer Col-F	4.9	4.9
112734 Match Control Ulcer Col-F	12.6	12.0
112384 Ulcer Col-F	6.6	10.2
112737 Match Control Ulcer Col-F	4.2	6.1
112386 Ulcer Col-F	0.5	1.2
112738 Match Control Ulcer Col-F	7.5	7.9
112381 Ulcer Col-M	0.1	0.1
112735 Match Control Ulcer Col-M	2.9	2.3
112382 Ulcer Col-M	6.7	8.4
112394 Match Control Ulcer Col-M	0.5	0.5
112383 Ulcer Col-M	12.1	14.6
112736 Match Control Ulcer Col-M	3.5	5.3
112423 Psoriasis-F	1.4	1.1
112427 Match Control Psoriasis-F	2.9	1.8
112418 Psoriasis-M	0.8	0.8
112723 Match Control Psoriasis-M	6.1	7.4
112419 Psoriasis-M	1.0	1.3
112424 Match Control Psoriasis-M	0.4	1.2
112420 Psoriasis-M	1.8	2.4
112425 Match Control Psoriasis-M	2.2	2.7
104689 (MF) OA Bone-Backus	12.1	13.2
104690 (MF) Adj “Normal”	5.4	4.2
Bone-Backus
104691 (MF) OA Synovium-Backus	43.2	35.6
104692 (BA) OA Cartilage-Backus	0.9	0.4
104694 (BA) OA Bone-Backus	16.8	16.7
104695 (BA) Adj “Normal”	6.5	6.1
Bone-Backus
104696 (BA) OA Synovium-Backus	24.0	24.1
104700 (SS) OA Bone-Backus	12.2	35.1
104701 (SS) Adj “Normal”	7.9	9.5
Bone-Backus
104702 (SS) OA Synovium-Backus	8.2	7.9
117093 OA Cartilage Rep7	2.0	2.3
112672 OA Bone5	1.9	0.8
112673 OA Synovium5	0.3	1.2
112674 OA Synovial Fluid cells5	0.5	0.4
117100 OA Cartilage Rep14	0.4	0.3
112756 OA Bone9	100.0	100.0
112757 OA Synovium9	0.5	0.2
112758 OA Synovial Fluid Cells9	0.8	1.5
117125 RA Cartilage Rep2	1.0	0.6
113492 Bone2 RA	2.8	3.6
113493 Synovium2 RA	1.7	0.7
113494 Syn Fluid Cells RA	0.9	2.1
113499 Cartilage4 RA	2.1	1.8
113500 Bone4 RA	1.8	2.5
113501 Synovium4 RA	2.1	2.3
113502 Syn Fluid Cells4 RA	1.0	0.8
113495 Cartilage3 RA	2.5	2.6
113496 Bone3 RA	2.0	2.1
113497 Synovium3 RA	1.4	1.4
113498 Syn Fluid Cells3 RA	2.9	3.2
117106 Normal Cartilage Rep20	0.1	0.7
113663 Bone3 Normal	0.3	0.1
113664 Synovium3 Normal	0.0	0.0
113665 Syn Fluid Cells3 Normal	0.1	0.2
117107 Normal Cartilage Rep22	0.9	0.3
113667 Bone4 Normal	0.4	0.7
113668 Synovium4 Normal	1.0	1.1
113669 Syn Fluid Cells4 Normal	1.0	0.7

[0760]

TABLE AD
CNS_neurodegeneration_v1.0
                               Rel.
                               Exp. (%)
                               Ag2100,
                               Run
Tissue Name                    207929343
AD 1 Hippo                     5.2
AD 2 Hippo                     9.3
AD 3 Hippo                     6.7
AD 4 Hippo                     7.2
AD 5 Hippo                     100.0
AD 6 Hippo                     16.5
Control 2 Hippo                17.7
Control 4 Hippo                3.4
Control (Path) 3 Hippo         4.4
AD 1 Temporal Ctx              15.7
AD 2 Temporal Ctx              26.4
AD 3 Temporal Ctx              12.3
AD 4 Temporal Ctx              24.3
AD 5 Inf Temporal Ctx          65.5
AD 5 Sup Temporal Ctx          20.9
AD 6 Inf Temporal Ctx          44.1
AD 6 Sup Temporal Ctx          59.0
Control 1 Temporal Ctx         9.5
Control 2 Temporal Ctx         34.6
Control 3 Temporal Ctx         0.0
Control 3 Temporal Ctx         10.4
Control (Path) 1 Temporal Ctx  68.8
Control (Path) 2 Temporal Ctx  49.7
Control (Path) 3 Temporal Ctx  8.5
Control (Path) 4 Temporal Ctx  55.5
AD 1 Occipital Ctx             31.6
AD 2 Occipital Ctx (Missing)   0.0
AD 3 Occipital Ctx             8.4
AD 4 Occipital Ctx             28.7
AD 5 Occipital Ctx             52.5
AD 6 Occipital Ctx             22.8
Control 1 Occipital Ctx        3.9
Control 2 Occipital Ctx        64.6
Control 3 Occipital Ctx        40.6
Control 4 Occipital Ctx        6.4
Control (Path) 1 Occipital Ctx 77.9
Control (Path) 2 Occipital Ctx 28.5
Control (Path) 3 Occipital Ctx 1.5
Control (Path) 4 Occipital Ctx 40.9
Control 1 Parietal Ctx         7.8
Control 2 Parietal Ctx         34.4
Control 3 Parietal Ctx         15.8
Control (Path) 1 Parietal Ctx  68.8
Control (Path) 2 Parietal Ctx  32.3
Control (Path) 3 Parietal Ctx  4.9
Control (Path) 4 Parietal Ctx  58.6

[0761]

TABLE AE
Panel 1.3D
                                 Rel.
                                 Exp. (%)
                                 Ag2100,
                                 Run
Tissue Name                      152517508
Liver adenocarcinoma             11.7
Pancreas                         0.0
Pancreatic ca. CAPAN 2           3.2
Adrenal gland                    1.4
Thyroid                          0.1
Salivary gland                   0.1
Pituitary gland                  2.1
Brain (fetal)                    2.1
Brain (whole)                    24.7
Brain (amygdala)                 11.2
Brain (cerebellum)               2.7
Brain (hippocampus)              36.3
Brain (substantia nigra)         1.5
Brain (thalamus)                 30.4
Cerebral Cortex                  100.0
Spinal cord                      2.5
glio/astro U87-MG                6.4
glio/astro U-118-MG              33.7
astrocytoma SW1783               5.9
neuro*; met SK-N-AS              14.5
astrocytoma SF-539               7.4
astrocytoma SNB-75               5.8
glioma SNB-19                    1.0
glioma U251                      2.4
glioma SF-295                    0.9
Heart (fetal)                    0.4
Heart                            0.1
Skeletal muscle (fetal)          3.4
Skeletal muscle                  0.1
Bone marrow                      5.4
Thymus                           2.1
Spleen                           0.6
Lymph node                       0.4
Colorectal                       1.8
Stomach                          1.0
Small intestine                  1.6
Colon ca. SW480                  13.1
Colon ca.* SW620 (SW480 met)     4.5
Colon ca. HT29                   4.1
Colon ca. HCT-116                5.0
Colon ca. CaCo-2                 5.9
Colon ca. tissue (ODO3866)       2.8
Colon ca. HCC-2998               3.7
Gastric ca.* (liver met) NCI-N87 2.3
Bladder                          0.9
Trachea                          0.7
Kidney                           0.7
Kidney (fetal)                   1.8
Renal ca. 786-0                  7.1
Renal ca. A498                   3.7
Renal ca. RXF 393                3.1
Renal ca. ACHN                   4.4
Renal ca. UO-31                  6.3
Renal ca. TK-10                  3.2
Liver                            0.0
Liver (fetal)                    3.8
Liver ca. (hepatoblast) HepG2    3.2
Lung                             0.3
Lung (fetal)                     0.9
Lung ca. (small cell) LX-1       6.6
Lung ca. (small cell) NCI-H69    8.5
Lung ca. (s. cell var.) SHP-77   7.5
Lung ca. (large cell) NCI-H460   0.0
Lung ca. (non-sm. cell) A549     0.2
Lung ca. (non-s. cell) NCI-H23   10.4
Lung ca. (non-s. cell) HOP-62    1.4
Lung ca. (non-s. cl) NCI-H522    5.3
Lung ca. (squam.) SW 900         3.2
Lung ca. (squam.) NCI-H596       7.2
Mammary gland                    0.2
Breast ca.* (pl. ef) MCF-7       5.6
Breast ca.* (pl. ef) MDA-MB-231  14.5
Breast ca.* (pl. ef) T47D        2.4
Breast ca. BT-549                6.8
Breast ca. MDA-N                 14.0
Ovary                            2.2
Ovarian ca. OVCAR-3              2.5
Ovarian ca. OVCAR-4              0.8
Ovarian ca. OVCAR-5              2.7
Ovarian ca. OVCAR-8              3.2
Ovarian ca. IGROV-1              2.0
Ovarian ca.* (ascites) SK-OV-3   7.4
Uterus                           0.0
Placenta                         0.2
Prostate                         0.2
Prostate ca.* (bone met) PC-3    2.0
Testis                           4.0
Melanoma Hs688(A).T              0.7
Melanoma* (met) Hs688(B).T       0.3
Melanoma UACC-62                 0.5
Melanoma M14                     7.2
Melanoma LOX IMVI                2.8
Melanoma* (met) SK-MEL-5         5.8
Adipose                          0.2

[0762]

TABLE AF
Panel 2.2
                                 Rel.
                                 Exp. (%)
                                 Ag2100,
                                 Run
Tissue Name                      174166901
Normal Colon                     6.3
Colon cancer (OD06064)           13.4
Colon Margin (OD06064)           9.0
Colon cancer (OD06159)           4.5
Colon Margin (OD06159)           5.9
Colon cancer (OD06297-04)        3.8
Colon Margin (OD06297-05)        9.9
CC Gr.2 ascend colon (ODO3921)   4.4
CC Margin (ODO3921)              2.8
Colon cancer metastasis (OD06104) 1.7
Lung Margin (OD06104)            3.1
Colon mets to lung (OD04451-01)  9.6
Lung Margin (OD04451-02)         3.2
Normal Prostate                  1.2
Prostate Cancer (OD04410)        0.0
Prostate Margin (OD04410)        0.7
Normal Ovary                     2.8
Ovarian cancer (OD06283-03)      11.7
Ovarian Margin (OD06283-07)      3.0
Ovarian Cancer 064008            1.1
Ovarian cancer (OD06145)         0.9
Ovarian Margin (OD06145)         0.0
Ovarian cancer (OD06455-03)      15.8
Ovarian Margin (OD06455-07)      1.8
Normal Lung                      1.2
Invasive poor diff. lung adeno (ODO4945-01 8.4
Lung Margin (ODO4945-03)         1.2
Lung Malignant Cancer (OD03126)  5.0
Lung Margin (OD03126)            0.6
Lung Cancer (OD05014A)           10.2
Lung Margin (OD05014B)           9.0
Lung cancer (OD06081)            10.1
Lung Margin (OD06081)            4.0
Lung Cancer (OD04237-01)         4.1
Lung Margin (OD04237-02)         2.0
Ocular Melanoma Metastasis       0.9
Ocular Melanoma Margin (Liver)   0.4
Melanoma Metastasis              10.4
Melanoma Margin (Lung)           2.0
Normal Kidney                    5.0
Kidney Ca, Nuclear grade 2 (OD04338) 15.4
Kidney Margin (OD04338)          5.0
Kidney Ca Nuclear grade 1/2 (OD04339) 100.0
Kidney Margin (OD04339)          9.3
Kidney Ca, Clear cell type (OD04340) 14.0
Kidney Margin (OD04340)          11.3
Kidney Ca, Nuclear grade 3 (OD04348) 9.0
Kidney Margin (OD04348)          30.4
Kidney malignant cancer (OD06204B) 3.6
Kidney normal adjacent tissue (OD06204E) 10.5
Kidney Cancer (OD04450-01)       2.4
Kidney Margin (OD04450-03)       13.3
Kidney Cancer 8120613            6.7
Kidney Margin 8120614            1.2
Kidney Cancer 9010320            1.7
Kidney Margin 9010321            4.5
Kidney Cancer 8120607            0.5
Kidney Margin 8120608            1.7
Normal Uterus                    1.1
Uterine Cancer 064011            1.5
Normal Thyroid                   0.0
Thyroid Cancer 064010            0.6
Thyroid Cancer A302152           5.3
Thyroid Margin A302153           0.0
Normal Breast                    3.0
Breast Cancer (OD04566)          8.1
Breast Cancer 1024               2.9
Breast Cancer (OD04590-01)       14.8
Breast Cancer Mets (OD04590-03)  3.2
Breast Cancer Metastasis (OD04655-05) 5.4
Breast Cancer 064006             3.1
Breast Cancer 9100266            2.6
Breast Margin 9100265            2.3
Breast Cancer A209073            1.8
Breast Margin A2090734           2.5
Breast cancer (OD06083)          17.1
Breast cancer node metastasis (OD06083) 14.7
Normal Liver                     0.4
Liver Cancer 1026                0.0
Liver Cancer 1025                1.8
Liver Cancer 6004-T              1.1
Liver Tissue 6004-N              2.5
Liver Cancer 6005-T              1.6
Liver Tissue 6005-N              0.0
Liver Cancer 064003              0.7
Normal Bladder                   2.9
Bladder Cancer 1023              1.5
Bladder Cancer A302173           17.8
Normal Stomach                   10.4
Gastric Cancer 9060397           1.1
Stomach Margin 9060396           0.7
Gastric Cancer 9060395           2.8
Stomach Margin 9060394           2.8
Gastric Cancer 064005            6.0

[0763]

TABLE AG
Panel 3D
                                 Rel.
                                 Exp (%)
                                 Ag2100,
                                 Run
Tissue Name                      164796104
Daoy- Medulloblastoma            7.3
TE671- Medulloblastoma           3.8
D283 Med- Medulloblastoma        15.7
PFSK-1- Primitive Neuroectodermal 11.2
XF-498- CNS                      21.2
SNB-78- Glioma                   11.3
SF-268- Glioblastoma             7.6
T98G- Glioblastoma               12.0
SK-N-SH- Neuroblastoma (metastasis) 5.6
SF-295- Glioblastoma             12.4
Cerebellum                       16.2
Cerebellum                       3.6
NCI-H292- Mucoepidermoid lung carcinoma 14.0
DMS-114- Small cell lung         10.4
cancer
DMS-79- Small cell lung cancer   100.0
NCI-H146- Small cell lung cancer 14.3
NCI-H526- Small cell lung cancer 19.8
NCI-N417- Small cell lung cancer 5.8
NCI-H82- Small cell lung cancer  10.2
NCI-H157- Squamous cell lung cancer (metastasis) 13.8
NCI-H1155- Large cell lung cancer 36.1
NCI-H1299- Large cell lung cancer 22.7
NCI-H727- Lung carcinoid         14.4
NCI-UMC-11- Lung carcinoid       25.9
LX-1- Small cell lung cancer     11.0
Colo-205- Colon cancer           12.7
KM12- Colon cancer               17.2
KM20L2- Colon cancer             7.0
NCI-H716- Colon cancer           19.5
SW-48- Colon adenocarcinoma      10.6
SW1116- Colon adenocarcinoma     7.7
LS 174T- Colon adenocarcinoma    9.8
SW-948- Colon adenocarcinoma     1.4
SW-480- Colon adenocarcinoma     7.6
NCI-SNU-5- Gastric carcinoma     14.9
KATO III- Gastric carcinoma      18.8
NCI-SNU-16- Gastric carcinoma    12.6
NCI-SNU-1- Gastric carcinoma     12.3
RF-1- Gastric adenocarcinoma     5.3
RF-48- Gastric adenocarcinoma    7.6
MKN-45- Gastric carcinoma        11.7
NCI-N87- Gastric carcinoma       9.3
OVCAR-5- Ovarian carcinoma       3.0
RL95-2- Uterine carcinoma        4.5
HelaS3- Cervical adenocarcinoma  9.0
Ca Ski- Cervical epidermoid carcinoma (metastasis) 21.0
ES-2- Ovarian clear cell carcinoma 11.7
Ramos- Stimulated with PMA/ionomycin 6 h 10.8
Ramos- Stimulated with PMA/ionomycin 14 h 6.2
MEG-01- Chronic myelogenous leukemia 5.8
(megokaryoblast)
Raji- Burkitt's lymphoma         6.7
Daudi- Burkitt's lymphoma        14.8
U266- B-cell plasmacytoma        5.1
CA46- Burkitt's lymphoma         5.0
RL- non-Hodgkin's B-cell lymphoma 3.8
JM1- pre-B-cell lymphoma         11.5
Jurkat- T cell leukemia          12.5
TF-1- Erythroleukemia            9.9
HUT 78- T-cell lymphoma          14.7
U937- Histiocytic lymphoma       8.1
KU-812- Myelogenous leukemia     17.7
769-P- Clear cell renal carcinoma 6.3
Caki-2- Clear cell renal carcinoma 9.5
SW 839- Clear cell renal carcinoma 5.2
G401- Wilms' tumor               6.3
Hs766T- Pancreatic carcinoma (LN metastasis) 15.7
CAPAN-1- Pancreatic adenocarcinoma (liver 8.6
metastasis)
SU86.86- Pancreatic carcinoma (liver metastasis) 14.1
BxPC-3- Pancreatic adenocarcinoma 9.4
HPAC- Pancreatic adenocarcinoma  14.5
MIA PaCa-2- Pancreatic carcinoma 2.6
CFPAC-1- Pancreatic ductal adenocarcinoma 38.7
PANC-1- Pancreatic epithelioid ductal carcinoma 19.5
T24- Bladder carcinma (transitional cell) 9.0
5637- Bladder carcinoma          10.5
HT-1197- Bladder carcinoma       4.8
UM-UC-3- Bladder carcinma (transitional cell) 13.3
A204- Rhabdomyosarcoma           15.2
HT-1080- Fibrosarcoma            11.9
MG-63- Osteosarcoma              7.3
SK-LMS-1- Leiomyosarcoma (vulva) 48.0
SJRH30- Rhabdomyosarcoma (met to bone marrow) 10.2
A431- Epidermoid carcinoma       12.2
WM266-4- Melanoma                21.9
DU 145- Prostate carcinoma (brain metastasis) 0.2
MDA-MB-468- Breast adenocarcinoma 5.6
SCC-4- Squamous cell carcinoma of tongue 0.3
SCC-9- Squamous cell carcinoma of tongue 0.3
SCC-15- Squamous cell carcinoma of tongue 0.2
CAL 27- Squamous cell carcinoma of tongue 19.9

[0764]

TABLE AH
Panel 4D
                                 Rel.
                                 Exp (%)
                                 Ag2100,
                                 Run
Tissue Name                      152800279
Secondary Th1 act                15.4
Secondary Th2 act                11.9
Secondary Tr1 act                15.6
Secondary Th1 rest               4.9
Secondary Th2 rest               3.3
Secondary Tr1 rest               6.0
Primary Th1 act                  13.6
Primary Th2 act                  12.0
Primary Tr1 act                  22.2
Primary Th1 rest                 100.0
Primary Th2 rest                 37.9
HUVEC IL-1beta                   12.2
HUVEC IFN gamma                  16.6
HUVEC TNF alpha + IFN gamma      11.8
HUVEC TNF alpha + IL4            11.4
HUVEC IL-11                      8.2
Lung Microvascular EC none       7.3
Lung Microvascular EC TNFalpha + IL-1beta 6.3
Microvascular Dermal EC none     23.3
Microsvasular Dermal EC TNFalpha + IL-1beta 10.5
Bronchial epithelium TNFalpha + IL1beta 0.6
Small airway epithelium none     1.6

[0765]

TABLE AI
Panel CNS_1
                           Rel.
                           Exp. (%)
                           Ag2100,
                           Run
Tissue Name                171649357
BA4 Control                23.8
BA4 Control2               19.1
BA4 Alzheimer's2           7.3
BA4 Parkinson's            43.8
BA4 Parkinson's2           60.7
BA4 Huntington's           23.3
BA4 Huntington's2          14.7
BA4 PSP                    13.8
BA4 PSP2                   26.2
BA4 Depression             15.4
BA4 Depression2            17.0
BA7 Control                36.6
BA7 Control2               17.4
BA7 Alzheimer's2           11.3
BA7 Parkinson's            21.9
BA7 Parkinson's2           36.1
BA7 Huntington's           56.3
BA7 Huntington's2          45.1
BA7 PSP                    44.4
BA7 PSP2                   17.6
BA7 Depression             8.5
BA9 Control                31.9
BA9 Control2               34.4
BA9 Alzheimer's            8.0
BA9 Alzheimer's2           20.0
BA9 Parkinson's            40.6
BA9 Parkinson's2           31.4
BA9 Huntington's           41.5
BA9 Huntington's2          21.8
BA9 PSP                    17.8
BA9 PSP2                   8.2
BA9 Depression             10.5
BA9 Depression2            16.2
BA17 Control               58.2
BA17 Control2              41.8
BA17 Alzheimer's2          27.0
BA17 Parkinson's           58.6
BA17 Parkinson's2          69.3
BA17 Huntington's          44.4
BA17 Huntington's2         31.9
BA17 Depression            13.6
BA17 Depression2           100.0
BA17 PSP                   35.4
BA17 PSP2                  18.3
Sub Nigra Control          11.6
Sub Nigra Control2         5.0
Sub Nigra Alzheimer's2     4.6
Sub Nigra Parkinson's2     11.8
Sub Nigra Huntington's     16.0
Sub Nigra Huntington's2    8.8
Sub Nigra PSP2             1.7
Sub Nigra Depression       2.7
Sub Nigra Depression2      8.0
Glob Palladus Control      8.4
Glob Palladus Control2     10.8
Glob Palladus Alzheimer's  1.8
Glob Palladus Alzheimer's2 8.3
Glob Palladus Parkinson's  51.1
Glob Palladus Parkinson's2 12.9
Glob Palladus PSP          9.3
Glob Palladus PSP2         9.9
Glob Palladus Depression   6.0
Temp Pole Control          9.8
Temp Pole Control2         21.5
Temp Pole Alzheimer's      6.6
Temp Pole Alzheimer's2     8.1
Temp Pole Parkinson's      33.0
Temp Pole Parkinson's2     24.8
Temp Pole Huntington's     33.2
Temp Pole PSP              8.8
Temp Pole PSP2             6.0
Temp Pole Depression2      17.0
Cing Gyr Control           23.3
Cing Gyr Control2          17.8
Cing Gyr Alzheimer's       7.3
Cing Gyr Alzheimer's2      10.4
Cing Gyr Parkinson's       13.4
Cing Gyr Parkinson's2      17.0
Cing Gyr Huntington's      28.3
Cing Gyr Huntington's2     10.6
Cing Gyr PSP               7.2
Cing Gyr PSP2              4.0
Cing Gyr Depression        6.9
Cing Gyr Depression2       10.4

[0766] AI.05 chondrosarcoma Summary: Ag2100 Highest expression of this gene is detected in untreated serum starved chondrosarcoma cell line (SW1353) (CT=27). Interestingly, expression of this gene appears to be somewhat down regulated upon IL-1 treatment, a potent activator of pro-inflammatory cytokines and matrix metalloproteinases which participate in the destruction of cartilage observed in Osteoarthritis (OA). Modulation of the expression of this transcript in chondrocytes by either small molecules or antisense might be important for preventing the degeneration of cartilage observed in OA

[0767] Al_comprehensive panel_v1.0 Summary: Ag2100 Highest expression of this gene is detected in osteoarthritis (OA) bone (CTs=27-28). This gene is highly expressed in bone isolated from 5 different osteoarthritic (OA) patients, synovium in 3 out of 5 OA patients, but not in cartilege from OA patients nor in any tissues from rheumatoid arthritis (RA) patients or control samples. Thus, small molecule therapeutics designed against the protein encoded for by this gene could reduce or inhibit inflammation. Anti-sense therapeutics that would block the translation of the transcript and protein production could also inhibit inflammatory processes. These types of therapeutics could be important in the treatment of diseases such as osteoarthritis

[0768] CNS_neurodegeneration_v1.0 Summary: Ag2100 This panel confirms the expression of this gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.3D for a discussion of this gene in treatment of central nervous system disorders.

[0769] Panel 1.3D Summary: Ag2100 Expression of this gene is highest in cerebral cortex (CT=26.3). This gene is expressed at moderate levels in all the regions of the CNS including amygdala, cerebellum, hippocampus, substantia nigra, thalamus, spinal cord, and fetal brain. This gene encodes a protein with homology to citron-kinase. Citron-kinase (Citron-K) has been proposed by in vitro studies to be a crucial effector of Rho in regulation of cytokinesis. Citron-K is essential for cytokinesis in vivo in specific neuronal precursors and may play a fundamental role in specific human malformative syndromes of the CNS (Di Cunto et al., 2000, Neuron 28:115-127, PMID: 11086988). General inhibitors of the RHO/RAC-INTERACTING CITRON KINASE family disrupt endothelial tight junctions, suggesting that specific modulators of this brain-preferential family member could be useful in delivery of therapeutics across the blood brain barrier. These general inhibitors also influence intracellular calcium flux, which is a central component of many important neuronal processes, such as apoptosis, neurotransmitter release and signal transduction (Jezior et al., 2001, Br. J. Pharmacol. 134:78-87, PMID: 11522599; Walsh et al., 2001, Gastroenterology 121:566-579, PMID: 11522741). Thus, modulators of the function of the protein encoded by this gene may prove useful in the treatment of neurodegenerative disorders involving apoptosis, such as spinal muscular atrophy, Alzheimer's disease, Huntington's disease, Parkinson's disease, and others. Diseases involving neurotransmitters or signal transduction, such as schizophrenia, mania, stroke, epilepsy and depression may also benefit from agents that modulate the function of the this gene product.

[0770] This gene also shows moderate to low expression in several metabolic tissues including adrenal gland, pituitary gland, gastrointestinal tract, fetal heart, fetal skeletal muscle and fetal liver. 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.

[0771] Interestingly, expression of this gene is higher in fetal tissues (CTs=31) as compared to the corresponding adult liver, and skeletal muscle (CTs=37-40). This observation suggests that expression of this gene can be used to distinguish fetal from adult liver and skeletal muscle. In addition, the relative overexpression of this gene in fetal tissue suggests that the protein product may enhance liver and muscle 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 liver and skeletal muscle related diseases.

[0772] 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, melanoma and brain cancers. Thus, 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, melanoma and brain cancers.

[0773] Panel 2.2 Summary: Ag2100 Expression of this gene is highest in a kidney cancer sample (CT=28). In addition, significant expression of this gene is also seen in a number of normal and cancer tissues including colon, lung, ovary, breast, kidney, thyroid, liver, bladder, and stomach. Interestingly, this gene is expressed at slightly higher levels in most of the tumors than in the normal matched tissue. Thus, expression of this gene could be used to distinguish between cancerous tissue and normal tissue. In addition, therapeutic modulation of this gene product, through the use of small molecule drugs or antibodies, might be of benefit in the treatment of cancer.

[0774] Panel 3D Summary: Ag2100 Expression of this gene is highest in a lung cancer cell line (CT=26). However, low to moderate expression is also seen in the majority of cancer cell lines on this panel, suggesting that this gene may play an important role in many cell types.

[0775] Panel 4D Summary: Ag2100 Highest expression of this gene is detected in resting primary Th1 cells (CT=24.5). Moderate to low levels of expression of this gene is seen in members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. Interestingly, this gene is highly induced in Ramos B cells treated with PMA and ionomycin, in non-transformed B cells and PBMC treated with PWM. All three of these observations are consistent with this gene being induced in B cells after activation. This gene product has homology to the RHO/RAC-interacting citron kinase. Thus citron kinase encoded by this gene may play an important role in T cell activation, by regulating TCR-mediated T cell spreading, chemotaxis and other chemokine responses and in apoptosis. Likewise, this putative kinase may also be important in B cell motility, antigen receptor mediated activation and apoptosis.

[0776] Small molecule therapeutics designed against the protein encoded for by this gene could reduce or inhibit inflammation. Anti-sense therapeutics that would block the translation of the transcript and protein production could also inhibit inflammatory processes. These types of therapeutics could be important in the treatment of diseases such as osteoarthritis. Likewise, these therapeutics could be important in the treatment of asthma, psoriasis, diabetes, and IBD, which require activated T cells, as well as diseases that involve B cell activation such as systemic lupus erythematosus.

[0777] Panel CNS—1 Summary: Ag2100 This panel confirms the expression of this gene at low levels in the brains of an independent group of individuals. Please see Panel 1.3D for a discussion of this gene in treatment of central nervous system disorders.

[0778] B. CG117662-02: Renal Renin Precursor Like.

[0779] Expression of gene CG117662-02 was assessed using the primer-probe sets Ag2078 and Ag5185, described in Tables BA and BB. Results of the RTQ-PCR runs are shown in Tables BC, BD, BE, BF and BG.

TABLE BA
Probe Name Ag2078
			Start	SEQ ID
Primers	Sequence	Length	Position	No
Forward	5′-accttcaaagtcgtctttgaca-3′	22	292	252
Probe	TET-5′-ctccaagtgcagccgtctctacactg-3′-TAMRA	26	342	253
Reverse	5′cgaagagcttgtgatacacaca-3′	22	370	254

[0780]

TABLE BB
Probe Name Ag5185
			Start	SEQ ID
Primers	Sequence	Length	Position	No
Forward	5′-ccgtgtctgtggggtcat-3′	18	491	255
Probe	TET-5′-attggtagacaccggtgcatcctaca-3′-TAMRA	26	540	256
Reverse	5′-tggagctggtagaacctgaga-3′	21	566	257

[0781]

TABLE BC
CNS_neurodegeneration_v1.0
                               Rel.
                               Exp. (%)
                               Ag5185,
                               Run
Tissue Name                    226559655
AD 1 Hippo                     5.7
AD 2 Hippo                     82.4
AD 3 Hippo                     11.4
AD 4 Hippo                     50.0
AD 5 Hippo                     22.5
AD 6 Hippo                     15.2
Control 2 Hippo                9.6
Control 4 Hippo                18.3
Control (Path) 3 Hippo         85.3
AD 1 Temporal Ctx              38.4
AD 2 Temporal Ctx              74.7
AD 3 Temporal Ctx              0.0
AD 4 Temporal Ctx              49.0
AD 5 Inf Temporal Ctx          31.6
AD 5 Sup Temporal Ctx          36.3
AD 6 Inf Temporal Ctx          55.5
AD 6 Sup Temporal Ctx          63.3
Control 1 Temporal Ctx         100.0
Control 2 Temporal Ctx         40.6
Control 3 Temporal Ctx         47.0
Control 3 Temporal Ctx         24.7
Control (Path) 1 Temporal Ctx  50.7
Control (Path) 2 Temporal Ctx  65.5
Control (Path) 3 Temporal Ctx  48.6
Control (Path) 4 Temporal Ctx  54.3
AD 1 Occipital Ctx             12.2
AD 2 Occipital Ctx (Missing)   0.0
AD 3 Occipital Ctx             18.8
AD 4 Occipital Ctx             19.8
AD 5 Occipital Ctx             12.1
AD 6 Occipital Ctx             25.0
Control 1 Occipital Ctx        26.2
Control 2 Occipital Ctx        3.6
Control 3 Occipital Ctx        40.6
Control 4 Occipital Ctx        20.9
Control (Path) 1 Occipital Ctx 39.2
Control (Path) 2 Occipital Ctx 18.3
Control (Path) 3 Occipital Ctx 0.0
Control (Path) 4 Occipital Ctx 0.0
Control 1 Parietal Ctx         46.7
Control 2 Parietal Ctx         0.0
Control 3 Parietal Ctx         12.2
Control (Path) 1 Parietal Ctx  65.5
Control (Path) 2 Parietal Ctx  23.8
Control (Path) 3 Parietal Ctx  0.0
Control (Path) 4 Parietal Ctx  57.4

[0782]

TABLE BD
General_screening_panel_v1.5
                                 Rel.
                                 Exp. (%)
                                 Ag5185,
                                 Run
Tissue Name                      228757766
Adipose                          1.0
Melanoma* Hs688(A).T             0.2
Melanoma* Hs688(B).T             0.1
Melanoma* M14                    0.1
Melanoma* LOXIMVI                0.1
Melanoma* SK-MEL-5               0.2
Squamous cell carcinoma SCC-4    0.4
Testis Pool                      8.4
Prostate ca.* (bone met) PC-3    1.5
Prostate Pool                    0.6
Placenta                         3.0
Uterus Pool                      1.5
Ovarian ca. OVCAR-3              0.9
Ovarian ca. SK-OV-3              0.2
Ovarian ca. OVCAR-4              0.7
Ovarian ca. OVCAR-5              4.7
Ovarian ca. IGROV-1              0.0
Ovarian ca. OVCAR-8              0.2
Ovary                            6.7
Breast ca. MCF-7                 0.5
Breast ca. MDA-MB-231            0.6
Breast ca. BT 549                0.2
Breast ca. T47D                  2.1
Breast ca. MDA-N                 0.0
Breast Pool                      5.0
Trachea                          1.0
Lung                             22.1
Fetal Lung                       0.6
Lung ca. NCI-N417                0.4
Lung ca. LX-1                    0.3
Lung ca. NCI-H146                0.0
Lung ca. SHP-77                  0.1
Lung ca. A549                    0.0
Lung ca. NCI-H526                0.5
Lung ca. NCI-H23                 1.4
Lung ca. NCI-H460                2.0
Lung ca. HOP-62                  0.1
Lung ca. NCI-H522                0.6
Liver                            1.0
Fetal Liver                      1.0
Liver ca. HepG2                  10.0
Kidney Pool                      4.2
Fetal Kidney                     100.0
Renal ca. 786-0                  0.0
Renal ca. A498                   0.0
Renal ca. ACHN                   0.2
Renal ca. UO-31                  0.3
Renal ca. TK-10                  0.0
Bladder                          0.5
Gastric ca. (liver met.) NCI-N87 1.1
Gastric ca. KATO III             0.3
Colon ca. SW-948                 18.2
Colon ca. SW480                  0.6
Colon ca.* (SW480 met) SW620     0.5
Colon ca. HT29                   1.6
Colon ca. HCT-116                0.5
Colon ca. CaCo-2                 0.2
Colon cancer tissue              2.6
Colon ca. SW1116                 0.1
Colon ca. Colo-205               0.0
Colon ca. SW-48                  0.8
Colon Pool                       4.7
Small Intestine Pool             4.0
Stomach Pool                     2.3
Bone Marrow Pool                 2.5
Fetal Heart                      0.2
Heart Pool                       1.6
Lymph Node Pool                  12.6
Fetal Skeletal Muscle            0.3
Skeletal Muscle Pool             0.4
Spleen Pool                      0.1
Thymus Pool                      3.8
CNS cancer (glio/astro) U87-MG   0.0
CNS cancer (glio/astro) U-118-MG 0.1
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         0.3
CNS cancer (glio) SF-295         0.5
Brain (Amygdala) Pool            0.4
Brain (cerebellum)               0.5
Brain (fetal)                    0.0
Brain (Hippocampus) Pool         0.2
Cerebral Cortex Pool             0.3
Brain (Substantia nigra) Pool    0.3
Brain (Thalamus) Pool            0.6
Brain (whole)                    0.8
Spinal Cord Pool                 0.5
Adrenal Gland                    2.6
Pituitary gland Pool             0.6
Salivary Gland                   0.5
Thyroid (female)                 0.1
Pancreatic ca. CAPAN2            0.2
Pancreas Pool                    4.9

[0783]

TABLE BE
Panel 1.3D
	Rel.	Rel.	Rel.
	Exp. (%)	Exp. (%)	Exp. (%)
	Ag2078,	Ag2078,	Ag2078,
	Run	Run	Run
Tissue Name	165626684	165627496	165678122
Liver adenocarcinoma	0.0	0.1	0.1
Pancreas	0.0	0.0	0.0
Pancreatic ca. CAPAN 2	0.0	0.0	0.2
Adrenal gland	0.5	0.5	0.3
Thyroid	0.0	0.0	0.0
Salivary gland	0.0	0.1	0.0
Pituitary gland	0.0	0.2	0.0
Brain (fetal)	0.0	0.0	0.0
Brain (whole)	0.0	0.0	0.1
Brain (amygdala)	0.1	0.0	0.0
Brain (cerebellum)	0.1	0.0	0.1
Brain (hippocampus)	0.0	0.3	0.0
Brain (substantia	0.0	0.0	0.1
nigra)
Brain (thalamus)	0.1	0.0	0.1
Cerebral Cortex	0.0	0.0	0.2
Spinal cord	0.0	0.0	0.0
glio/astro U87-MG	0.0	0.0	0.0
glio/astro U-118-MG	0.0	0.0	0.0
astrocytoma SW1783	0.0	0.0	0.1
neuro*; met SK-N-AS	0.0	0.1	0.0
astrocytoma SF-539	0.0	0.0	0.0
astrocytoma SNB-75	0.0	0.0	0.2
glioma SNB-19	0.0	0.0	0.0
glioma U251	0.0	0.0	0.0
glioma SF-295	0.0	0.0	0.0
Heart (fetal)	0.0	0.0	0.0
Heart	0.0	0.0	0.0
Skeletal muscle	0.0	0.0	0.0
(fetal)
Skeletal muscle	0.0	0.0	0.0
Bone marrow	0.0	0.0	0.0
Thymus	0.0	0.0	0.0
Spleen	0.0	0.0	0.0
Lymph node	0.0	0.1	0.0
Colorectal	0.0	0.0	0.0
Stomach	0.0	0.0	0.1
Small intestine	0.1	0.0	0.0
Colon ca. SW480	0.0	0.0	0.0
Colon ca.* SW620	0.0	0.0	0.0
(SW480 met)
Colon ca. HT29	0.2	0.3	0.3
Colon ca. HCT-116	0.0	0.0	0.0
Colon ca. CaCo-2	0.0	0.0	0.0
Colon ca. tissue	0.2	0.1	0.5
(ODO3866)
Colon ca. HCC-2998	0.1	0.3	0.1
Gastric ca.* (liver	0.0	0.1	0.0
met) NCI-N87
Bladder	0.0	0.0	0.0
Trachea	0.1	0.0	0.0
Kidney	11.2	10.8	8.7
Kidney (fetal)	100.0	100.0	100.0
Renal ca. 786-0	0.0	0.0	0.0
Renal ca. A498	0.0	0.0	0.1
Renal ca. RXF 393	0.0	0.0	0.0
Renal ca. ACHN	0.0	0.0	0.0
Renal ca. UO-31	0.0	0.0	0.1
Renal ca. TK-10	0.0	0.1	0.0
Liver	0.3	0.3	0.0
Liver (fetal)	0.6	0.7	0.5
Liver ca.	0.0	0.0	0.0
(hepatoblast) HepG2
Lung	0.0	0.0	0.1
Lung (fetal)	0.1	0.1	0.0
Lung ca. (small	0.0	0.0	0.0
cell) LX-1
Lung ca. (small	0.0	0.0	0.0
cell) NCI-H69
Lung ca. (s. cell	0.0	0.1	0.0
var.) SHP-77
Lung ca. (large	0.0	0.0	0.0
cell) NCI-H460
Lung ca. (non-sm.	0.0	0.0	0.0
cell) A549
Lung ca. (non-s.	0.0	0.0	0.0
cell) NCI-H23
Lung ca. (non-s.	0.1	0.0	0.0
cell) HOP-62
Lung ca. (non-s.	0.0	0.0	0.0
cl) NCI-H522
Lung ca. (squam.) SW	0.1	0.1	0.0
900
Lung ca. (squam.)	0.0	0.0	0.0
NCI-H596
Mammary gland	0.2	0.2	0.1
Breast ca.* (pl.	0.0	0.0	0.1
ef) MCF-7
Breast ca.* (pl.	0.1	0.0	0.0
ef) MDA-MB-231
Breast ca.* (pl.	0.1	0.0	0.0
ef) T47D
Breast ca. BT-549	0.0	0.0	0.0
Breast ca. MDA-N	0.0	0.0	0.0
Ovary	0.6	0.8	0.6
Ovarian ca. OVCAR-3	0.1	0.1	0.0
Ovarian ca. OVCAR-4	0.0	0.1	0.0
Ovarian ca. OVCAR-5	0.2	0.2	0.1
Ovarian ca. OVCAR-8	0.0	0.0	0.0
Ovarian ca. IGROV-1	0.0	0.0	0.0
Ovarian ca.* (ascites)	0.0	0.0	0.0
SK-OV-3
Uterus	1.7	1.1	1.1
Placenta	0.7	1.2	0.7
Prostate	0.1	0.0	0.1
Prostate ca.*	0.2	0.2	0.0
(bone met) PC-3
Testis	0.2	0.1	0.2
Melanoma Hs688(A).T	0.0	0.0	0.0
Melanoma* (met)	0.0	0.0	0.0
Hs688(B).T
Melanoma UACC-62	0.0	0.0	0.0
Melanoma M14	0.0	0.0	0.0
Melanoma LOX IMVI	0.0	0.0	0.1
Melanoma* (met)	0.0	0.0	0.0
SK-MEL-5
Adipose	0.0	0.2	0.0

[0784]

TABLE BF
Panel 4D
                                 Rel.
                                 Exp. (%)
                                 Ag2078,
                                 Run
Tissue Name                      161905846
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        0.8
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          0.1
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                        0.1
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       0.2
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                       0.4
HUVEC starved                    0.2
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       0.2
Lung Microvascular EC TNFalpha + IL-1beta 0.2
Microvascular Dermal EC none     0.3
Microsvasular Dermal EC TNFalpha + IL-1beta 0.1
Bronchial epithelium TNFalpha + IL1beta 0.1
Small airway epithelium none     0.0
Small airway epithelium TNFalpha + IL-1beta 0.5
Coronery artery SMC rest         0.1
Coronery artery SMC TNFalpha + IL-1beta 0.1
Astrocytes rest                  0.0
Astrocytes TNFalpha + IL-1beta   0.1
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                  0.4
Lupus kidney                     3.9
NCI-H292 none                    1.3
NCI-H292 IL-4                    0.5
NCI-H292 IL-9                    1.9
NCI-H292 IL-13                   0.3
NCI-H292 IFN gamma               1.0
HPAEC none                       0.0
HPAEC TNF alpha + IL-1beta       0.0
Lung fibroblast none             0.0
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   5.9
Dermal fibroblast CCD1070 TNF alpha 4.5
Dermal fibroblast CCD1070 IL-1 beta 3.1
Dermal fibroblast IFN gamma      0.0
Dermal fibroblast IL-4           0.0
IBD Colitis 2                    0.0
IBD Crohn's                      0.0
Colon                            0.0
Lung                             0.2
Thymus                           100.0
Kidney                           0.4

[0785]

TABLE BG
Panel 5D
                                 Rel.
                                 Exp. (%)
                                 Ag2078,
                                 Run
Tissue Name                      168095527
97457_Patient-02go_adipose       11.7
97476_Patient-07sk_skeletal muscle 0.0
97477_Patient-07ut uterus        2.8
97478_Patient-07pl_placenta      12.9
97481_Patient-08sk_skeletal muscle 0.0
97482_Patient-08ut_uterus        22.8
97483_Patient-08pl_placenta      4.5
97486_Patient-09sk_skeletal muscle 0.0
97487_Patient-09ut_uterus        0.0
97488_Patient-09pl_placenta      2.7
97492_Patient-10ut_uterus        100.0
97493_Patient-10pl_placenta      5.4
97495_Patient-11go_adipose       6.0
97496_Patient-11sk_skeletal muscle 0.0
97497 Patient-11ut_uterus        12.8
97498_Patient-11pl_placenta      8.5
97500_Patient-12go_adipose       87.1
97501_Patient-12sk_skeletal muscle 0.0
97502_Patient-12ut_uterus        4.6
97503_Patient-12pl_placenta      8.0
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     1.0
94713_Donor 2 AD - B_adipose     0.0
94714_Donor 2 AD - C_adipose     0.0
94742_Donor 3 U - A_Mesenchymal Stem Cells 0.0
94743_Donor 3 U - B_Mesenchymal Stem Cells 0.0
94730_Donor 3 AM - A_adipose     0.9
94731_Donor 3 AM - B_adipose     0.0
94732_Donor 3 AM - C_adipose     0.0
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) 0.0
81735_Small Intestine            0.0
72409_Kidney_Proximal Convoluted Tubule 0.0
82685_Small intestine_Duodenum   0.0
90650_Adrenal_Adrenocortical adenoma 0.0
72410_Kidney_HRCE                1.1
72411_Kidney_HRE                 5.3
73139_Uterus_Uterine smooth muscle cells 2.4

[0786] CNS_neurodegeneration_v1.0 Summary: Ag5185 Low levels of expression of this gene is seen in control temporal cortex and in a hippocampus sample from an Alzheimer patient (CTs=34.6-34.9). Therefore, therapeutic modulation of this gene may be useful in the neurological disorders including seizure and memory related diseases.

[0787] General_screening_panel_v1.5 Summary: Ag5185 Highest expression of this gene is detected in fetal kidney (CT=26.7). Interestingly, expression of this gene is higher in fetal as compared to adult kidney (CT=31). This observation suggests that expression of this gene can be used to distinguish fetal from adult kidney and also from other samples in this panel. In addition, the relative overexpression of this gene in fetal tissue suggests that the protein product may enhance kidney 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 kidney related diseases including lupus and glomerulonephritis.

[0788] Moderate to low levels of expression of this gene is also seen in tissues with metabolic/endocrine functions such as pancreas, adiposes, adrenal and pituitary glands, heart, skeletal muscle, and gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0789] Moderate to low levels of expression of this gene is also seen in a number of cancer cell lines derived from colon, lung, and ovarian cancer. Therefore, therapeutic modulation of this gene may be useful in the treatment of colon, lung and ovarian cancers.

[0790] Panel 1.3D Summary: Ag2078 Three experiments with same probe-primer sets are in excellent agreement. Highest expression of this gene is seen in fetal kidney (CTs=26-27.8), with lower expression in the adult lung. This pattern correlates to the expression seen in panel 1.5. Please see panel 1.5 for further discussion of this gene.

[0791] Panel 4D Summary: Ag2078 Highest expression of this gene is detected in thymus (CT=27.3). This gene or its protein product may thus 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.

[0792] Moderate to low levels of expression of this gene is also seen in lupus kidney, resting and cytokine activated mucoepidermoid NCI-H292 cells and dermal fibroblasts. Therefore, therapeutic modulation of this gene may be useful in the treatment of chronic obstructive pulmonary disease, asthma, allergy, emphysema, lupus kidney and skin disorders, including psoriasis.

[0793] Panel 5D Summary: Ag2078 Highest expression of this gene is detected in uterus and adipose of diabetic patients on insulin (CT=30.9-31). In addition, moderate to low levels of expression of this gene is also seen in uterus and placenta. Therefore, therapeutic modulation of this gene may be useful in the treatment of obesity and diabetes.

[0794] C. CG118051-02: ALDH8 Splice Variant, Submitted to Study DDSMT on Sep. 26, 2001 by Saguo; Classification Type=Finished In-Silico; Novelty=Update-Variants; ORF Start=407, ORF Stop=1436, Frame=2; 1586 bp.

[0795] Expression of gene CG118051-02 was assessed using the primer-probe set Ag3729, described in Table CA. Results of the RTQ-PCR runs are shown in Tables CB and CC.

TABLE CA
Probe Name Ag3729
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-ttcaagaaaacaagcagcttct-3′	22	273	258
Probe	TET-5′-cccaggacctgcataagccagct-3′-TAMRA	23	309	259
Reverse	5′-ctcagatatqtctgcctcgaa-3′	21	332	260

[0796]

TABLE CB
Panel 2.2
	Rel.	Rel.
	Exp. (%)	Exp. (%)
	Ag3729,	Ag3729,
	Run	Run
Tissue Name	174441818	259034396
Normal Colon	0.4	0.3
Colon cancer (OD06064)	1.4	1.0
Colon Margin (OD06064)	0.0	0.0
Colon cancer (OD06159)	0.2	0.1
Colon Margin (OD06159)	0.0	0.0
Colon cancer (OD06297-04)	0.0	0.0
Colon Margin (OD06297-05)	0.0	0.0
CC Gr.2 ascend colon (ODO3921)	1.1	0.8
CC Margin (ODO3921)	0.0	0.0
Colon cancer metastasis (OD06104)	0.2	0.1
Lung Margin (OD06104)	0.0	0.0
Colon mets to lung (OD04451-01)	0.2	0.2
Lung Margin (OD04451-02)	0.0	0.0
Normal Prostate	2.3	1.8
Prostate Cancer (OD04410)	2.2	1.6
Prostate Margin (OD04410)	5.1	3.8
Normal Ovary	0.7	0.3
Ovarian cancer (OD06283-03)	2.5	1.7
Ovarian Margin (OD06283-07)	0.0	0.0
Ovarian Cancer 064008	1.0	0.6
Ovarian cancer (OD06145)	0.4	0.3
Ovarian Margin (OD06145)	0.5	0.3
Ovarian cancer (OD06455-03)	0.9	0.5
Ovarian Margin (OD06455-07)	0.0	0.0
Normal Lung	0.0	0.0
Invasive poor diff. lung adeno	9.2	7.5
(ODO4945-01
Lung Margin (ODO4945-03)	0.0	0.0
Lung Malignant Cancer (OD03126)	0.5	0.4
Lung Margin (OD03126)	0.4	0.3
Lung Cancer (OD05014A)	0.0	0.0
Lung Margin (OD05014B)	0.8	0.6
Lung cancer (OD06081)	44.8	0.3
Lung Margin (OD06081)	0.0	0.0
Lung Cancer (OD04237-01)	3.1	2.6
Lung Margin (OD04237-02)	0.4	0.3
Ocular Melanoma Metastasis	0.0	0.0
Ocular Melanoma Margin (Liver)	0.0	0.0
Melanoma Metastasis	0.0	0.0
Melanoma Margin (Lung)	0.3	0.2
Normal Kidney	0.0	0.0
Kidney Ca, Nuclear grade 2 (OD04338)	1.5	1.2
Kidney Margin (OD04338)	0.4	0.3
Kidney Ca Nuclear grade 1/2 (OD04339)	0.0	0.0
Kidney Margin (OD04339)	0.0	0.0
Kidney Ca, Clear cell type (OD04340)	0.0	0.0
Kidney Margin (OD04340)	0.4	0.3
Kidney Ca, Nuclear grade 3 (OD04348)	0.0	0.0
Kidney Margin (OD04348)	0.0	0.0
Kidney malignant cancer (OD06204B)	0.0	0.0
Kidney normal adjacent tissue	0.0	0.0
(OD06204E)
Kidney Cancer (OD04450-01)	0.0	0.0
Kidney Margin (OD04450-03)	1.3	0.9
Kidney Cancer 8120613	0.0	0.0
Kidney Margin 8120614	0.0	0.0
Kidney Cancer 9010320	0.5	0.3
Kidney Margin 9010321	1.8	1.4
Kidney Cancer 8120607	0.0	0.0
Kidney Margin 8120608	1.0	0.8
Normal Uterus	0.0	0.0
Uterine Cancer 064011	1.8	1.2
Normal Thyroid	0.0	0.0
Thyroid Cancer 064010	0.0	0.0
Thyroid Cancer A302152	0.0	0.0
Thyroid Margin A302153	0.0	0.0
Normal Breast	9.2	6.5
Breast Cancer (OD04566)	17.4	12.9
Breast Cancer 1024	100.0	100.0
Breast Cancer (OD04590-01)	3.9	2.5
Breast Cancer Mets (OD04590-03)	1.2	0.9
Breast Cancer Metastasis (OD04655-05)	48.6	34.4
Breast Cancer 064006	2.4	2.1
Breast Cancer 9100266	55.1	43.8
Breast Margin 9100265	14.7	10.8
Breast Cancer A209073	32.1	24.5
Breast Margin A2090734	9.1	6.4
Breast cancer (OD06083)	69.7	61.6
Breast cancer node metastasis	28.5	23.3
(OD06083)
Normal Liver	0.0	0.0
Liver Cancer 1026	0.0	0.0
Liver Cancer 1025	0.8	0.6
Liver Cancer 6004-T	0.2	0.1
Liver Tissue 6004-N	0.4	0.3
Liver Cancer 6005-T	0.0	0.0
Liver Tissue 6005-N	0.0	0.0
Liver Cancer 064003	0.0	0.0
Normal Bladder	0.0	0.0
Bladder Cancer 1023	3.2	2.3
Bladder Cancer A302173	4.5	3.2
Normal Stomach	0.0	0.0
Gastric Cancer 9060397	0.5	0.3
Stomach Margin 9060396	2.1	1.4
Gastric Cancer 9060395	2.5	1.7
Stomach Margin 9060394	1.8	1.1
Gastric Cancer 064005	0.0	0.0

[0797]

TABLE CC
Panel 4.1D
                                 Rel.
                                 Exp. (%)
                                 Ag3729,
                                 Run
Tissue Name                      170222887
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              7.4
Ramos (B cell) ionomycin         3.1
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 26.8
Small airway epithelium none     25.5
Small airway epithelium TNFalpha + IL-1beta 46.7
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 6.7
Liver cirrhosis                  0.0
NCI-H292 none                    100.0
NCI-H292 IL-4                    55.9
NCI-H292 IL-9                    82.9
NCI-H292 IL-13                   58.2
NCI-H292 IFN gamma               60.3
HPAEC none                       0.0
HPAEC TNF alpha + IL-1 beta      0.0
Lung fibroblast none             0.0
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
Dermal Fibroblasts rest          0.0
Neutrophils TNFa + LPS           0.0
Neutrophils rest                 0.0
Colon                            0.0
Lung                             6.3
Thymus                           7.8
Kidney                           2.6

[0798] CNS_neurodegeneration_v1.0 Summary: Ag3729 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0799] Panel 2.2 Summary: Ag3729 Two experiments with same probe-primer sets are in good agreement. Highest expression of this gene is seen in breast cancer (CTs=27-29). Thus, expression of this gene could be used to differentiate between the breast cancer samples and other samples on this panel.

[0800] In addition, moderate expression of this gene is also seen in cancer samples derived from colon, breast, ovarian, lung, bladder, kidney and uterine cancers. Interestingly, expression of gene higher cancer compared to the corresponding normal adjacent tissue. Thus, expression of this gene may be used as diagnostic marker to detect the presence of colon, breast, ovarian, lung, bladder, kidney and uterine cancers and also, therapeutic modulation of the expression or function of this gene may be effective in the treatment of these cancers.

[0801] Panel 4.1D Summary: Ag3729 Expression of this gene is restricted to a few samples, with highest expression is seen in untreated NCI-H292 cells (CT=31.4). The gene is also expressed in a cluster of treated and untreated samples derived from the NCI-H292 cell line, a human airway epithelial cell line that produces mucins. Mucus overproduction is an important feature of bronchial asthma and chronic obstructive pulmonary disease samples. Interestingly, the transcript is also expressed at lower but still significant levels in small airway and bronchial epithelium treated with IL-1 beta and TNF-alpha and untreated small airway epithelium. The expression of the transcript in this mucoepidermoid cell line that is often used as a model for airway epithelium (NCI-H292 cells) suggests that this transcript may be important in the proliferation or activation of airway epithelium. Therefore, therapeutics designed with the protein encoded by the transcript may reduce or eliminate symptoms caused by inflammation in lung epithelia in chronic obstructive pulmonary disease, asthma, allergy, and emphysema.

[0802] D. CG140468-02: Serine/Threonine-Protein Kinase Pak 1.

[0803] Expression of gene CG140468-02 was assessed using the primer-probe set Ag7054, described in Table DA. Results of the RTQ-PCR runs are shown in Table DB. Please note that CG140468-02 represents a full-length physical clone.

TABLE DA
Probe Name Ag7054
			Start	SEQ ID
Primers	Sequence	Length	Position	No
Forward	5′-ggtttgagaagattgccaagc-3′	21	819	261
Probe	TET-5′-cctcactccactgattgctgcagctaa-3′-TAMRA	27	850	262
Reverse	5′-ctggggtgagtgtggttttag-3′	21	898	263

[0804]

TABLE DB
General_screening_panel_v1.6
                                 Rel.
                                 Exp. (%)
                                 Ag7054,
                                 Run
Tissue Name                      282273878
Adipose                          3.6
Melanoma* Hs688(A).T             7.3
Melanoma* Hs688(B).T             6.6
Melanoma* M14                    13.3
Melanoma* LOXIMVI                21.6
Melanoma* SK-MEL-5               8.1
Squamous cell carcinoma SCC-4    7.7
Testis Pool                      5.6
Prostate ca.* (bone met) PC-3    3.3
Prostate Pool                    8.0
Placenta                         9.5
Uterus Pool                      2.4
Ovarian ca. OVCAR-3              100.0
Ovarian ca. SK-OV-3              16.4
Ovarian ca. OVCAR-4              3.3
Ovarian ca. OVCAR-5              35.1
Ovarian ca. IGROV-1              5.3
Ovarian ca. OVCAR-8              8.4
Ovary                            5.1
Breast ca. MCF-7                 2.2
Breast ca. MDA-MB-231            11.8
Breast ca. BT 549                4.2
Breast ca. T47D                  7.7
Breast ca. MDA-N                 5.8
Breast Pool                      8.8
Trachea                          7.7
Lung                             4.1
Fetal Lung                       7.9
Lung ca. NCI-N417                7.9
Lung ca. LX-1                    19.9
Lung ca. NCI-H146                3.5
Lung ca. SHP-77                  5.8
Lung ca. A549                    8.8
Lung ca. NCI-H526                3.5
Lung ca. NCI-H23                 11.0
Lung ca. NCI-H460                1.0
Lung ca. HOP-62                  3.5
Lung ca. NCI-H522                20.7
Liver                            0.7
Fetal Liver                      9.1
Liver ca. HepG2                  0.5
Kidney Pool                      11.3
Fetal Kidney                     16.0
Renal ca. 786-0                  9.9
Renal ca. A498                   4.4
Renal ca. ACHN                   6.9
Renal ca. UO-31                  13.5
Renal ca.TK-10                   10.7
Bladder                          9.0
Gastric ca. (liver met.) NCI-N87 30.6
Gastric ca. KATO III             49.3
Colon ca. SW-948                 7.8
Colon ca. SW480                  2.5
Colon ca.* (SW480 met) SW620     11.8
Colon ca. HT29                   22.2
Colon ca. HCT-116                19.1
Colon ca. CaCo-2                 34.6
Colon cancer tissue              9.0
Colon ca. SW1116                 4.5
Colon ca. Colo-205               10.2
Colon ca. SW-48                  8.0
Colon Pool                       9.1
Small Intestine Pool             8.9
Stomach Pool                     5.1
Bone Marrow Pool                 3.4
Fetal Heart                      1.5
Heart Pool                       3.7
Lymph Node Pool                  8.3
Fetal Skeletal Muscle            8.1
Skeletal Muscle Pool             4.3
Spleen Pool                      5.1
Thymus Pool                      7.6
CNS cancer (glio/astro) U87-MG   6.3
CNS cancer (glio/astro) U-118-MG 12.7
CNS cancer (neuro; met) SK-N-AS  6.2
CNS cancer (astro) SF-539        7.4
CNS cancer (astro) SNB-75        14.1
CNS cancer (glio) SNB-19         5.5
CNS cancer (glio) SF-295         5.8
Brain (Amygdala) Pool            24.8
Brain (cerebellum)               85.9
Brain (fetal)                    16.4
Brain (Hippocampus) Pool         21.2
Cerebral Cortex Pool             64.6
Brain (Substantia nigra) Pool    27.9
Brain (Thalamus) Pool            51.8
Brain (whole)                    55.5
Spinal Cord Pool                 5.0
Adrenal Gland                    4.9
Pituitary gland Pool             4.9
Salivary Gland                   2.7
Thyroid (female)                 5.8
Pancreatic ca. CAPAN2            9.7
Pancreas Pool                    5.5

[0805] General_screening_panel_v1.6 Summary: Ag7054 Highest expression of this gene is detected in a ovarian cancer cell line (CT=25.4). 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.

[0806] 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.

[0807] 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.

[0808] Interestingly, this gene is expressed at much higher levels in fetal (CT=28.9) when compared to adult liver (CT=32.7). This observation suggests that expression of this gene can be used to distinguish fetal from adult liver. 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 protein encoded by this gene could be useful in treatment of liver related diseases.

[0809] E. CG142564-01: Carnitine O-Palmitoyltransferase I.

[0810] Expression of gene CG142564-01 was assessed using the primer-probe set Ag6952, described in Table EA. Results of the RTQ-PCR runs are shown in Table EB. Please note that CG142564-02 represents a full-length physical clone.

TABLE EA
Probe Name Ag6952
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-tctgctaccaatcccagatcc-3′	21	434	264
Probe	TET-5′-tcgacccagagcagcacccca-3′-TAMRA	21	461	265
Reverse	5′-catctgctacagggccaaag-3′	20	504	266

[0811]

TABLE EB
General_screening_panel_v1.6
                                 Rel.
                                 Exp. (%)
                                 Ag6952,
                                 Run
Tissue Name                      278388893
Adipose                          4.1
Melanoma* Hs688(A).T             0.8
Melanoma* Hs688(B).T             1.2
Melanoma* M14                    21.8
Melanoma* LOXIMVI                4.6
Melanoma* SK-MEL-5               8.5
Squamous cell carcinoma SCC-4    1.6
Testis Pool                      31.6
Prostate ca.* (bone met) PC-3    9.3
Prostate Pool                    5.8
Placenta                         8.5
Uterus Pool                      0.7
Ovarian ca. OVCAR-3              5.0
Ovarian ca. SK-OV-3              50.7
Ovarian ca. OVCAR-4              1.9
Ovarian ca. OVCAR-5              25.3
Ovarian ca. IGROV-1              6.9
Ovarian ca. OVCAR-8              4.7
Ovary                            3.0
Breast ca. MCF-7                 9.7
Breast ca. MDA-MB-231            9.1
Breast ca. BT 549                14.3
Breast ca. T47D                  3.3
Breast ca. MDA-N                 0.8
Breast Pool                      3.1
Trachea                          3.8
Lung                             3.0
Fetal Lung                       7.3
Lung ca. NCI-N417                1.2
Lung ca. LX-1                    22.8
Lung ca. NCI-H146                3.6
Lung ca. SHP-77                  26.4
Lung ca. A549                    13.4
Lung ca. NCI-H526                0.8
Lung ca. NCI-H23                 13.8
Lung ca. NCI-H460                13.9
Lung ca. HOP-62                  32.8
Lung ca. NCI-H522                21.6
Liver                            0.4
Fetal Liver                      2.2
Liver ca. HepG2                  5.0
Kidney Pool                      2.7
Fetal Kidney                     4.6
Renal ca. 786-0                  14.6
Renal ca. A498                   1.8
Renal ca. ACHN                   7.6
Renal ca. UO-31                  11.9
Renal ca. TK-10                  20.0
Bladder                          33.4
Gastric ca. (liver met.) NCI-N87 81.2
Gastric ca. KATO III             8.2
Colon ca. SW-948                 5.4
Colon ca. SW480                  14.8
Colon ca.* (SW480 met) SW620     17.1
Colon ca. HT29                   1.3
Colon ca. HCT-116                14.3
Colon ca. CaCo-2                 6.7
Colon cancer tissue              7.6
Colon ca. SW1116                 4.4
Colon ca. Colo-205               4.7
Colon ca. SW-48                  2.6
Colon Pool                       3.4
Small Intestine Pool             2.9
Stomach Pool                     2.9
Bone Marrow Pool                 1.5
Fetal Heart                      100.0
Heart Pool                       42.6
Lymph Node Pool                  2.9
Fetal Skeletal Muscle            17.9
Skeletal Muscle Pool             21.8
Spleen Pool                      10.4
Thymus Pool                      17.9
CNS cancer (glio/astro) U87-MG   12.3
CNS cancer (glio/astro) U-118-MG 25.3
CNS cancer (neuro; met) SK-N-AS  21.0
CNS cancer (astro) SF-539        2.6
CNS cancer (astro) SNB-75        16.5
CNS cancer (glio) SNB-19         10.1
CNS cancer (glio) SF-295         61.1
Brain (Amygdala) Pool            4.5
Brain (cerebellum)               39.0
Brain (fetal)                    13.2
Brain (Hippocampus) Pool         3.6
Cerebral Cortex Pool             3.4
Brain (Substantia nigra) Pool    5.3
Brain (Thalamus) Pool            5.6
Brain (whole)                    3.3
Spinal Cord Pool                 4.8
Adrenal Gland                    6.9
Pituitary gland Pool             3.2
Salivary Gland                   4.9
Thyroid (female)                 1.1
Pancreatic ca. CAPAN2            12.1
Pancreas Pool                    5.0

[0812] General_screening_panel_v1.6 Summary: Ag6952 Highest expression of this gene is detected in fetal heart (CT=26.7). Moderate to high levels of expression of this gene is also seen in tissues with metabolic/endocrine functions such as 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.

[0813] 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.

[0814] 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.

[0815] F. CG142797-01: Cathepsin L Like.

[0816] Expression of gene CG142797-01 was assessed using the primer-probe set Ag7539, described in Table FA.

TABLE FA
Probe Name Ag7539
			Start	SEQ ID
Primers	Sequencs	Length	Position	No
Forward	5′-ctctaacacgtgaccacagtctaga- 3′	25	68	267
Probe	TET-5′-tcttgtgctttgccttccacttggt-3′-TAMRA	25	103	268
Reverse	5′-atcttcatgttctccatgtcatataatc-3′	28	128	269

[0817] CNS_neurodegeneration_v1.0 Summary: Ag7539 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0818] Panel 4.1D Summary: Ag7539 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0819] G. CG143216-01: Diacylglycerol Kinase.

[0820] Expression of gene CG143216-01 was assessed using the primer-probe sets Ag4554 and Ag7230, described in Tables GA and GB. Results of the RTQ-PCR runs are shown in Tables GC, GD, GE and GF.

TABLE GA
Probe Name Ag4554
			Start	SEQ ID
Primers	Sequence	Length	Position	No
Forward	5′-aatgctccaggttcaattttct-3′	22	1349	270
Probe	TET-5′-accaaccagcaggaccagtttgactt-3′-TAMRA	26	1390	271
Reverse	5′-gacgcgataaacttcaacaaaa-3′	22	1419	272

[0821]

TABLE GB
Probe Name Ag7230
			Start	SEQ ID
Primers	Sequence	Length	Position	No
Forward	5′-gcatatcgttgttggggact-3′	20	852	273
Probe	TET-5′-atggatgtgtcctcagtccaccacaa-3′-TAMRA	26	880	274
Reverse	5′-cacggagtagcgaaggagtg-3′	20	911	275

[0822]

TABLE GC
CNS_neurodegeneration_v1.0
		Rel.	Rel.
		Exp. (%)	Exp. (%)
		Ag4554,	Ag7230,
		Run	Run
	Tissue Name	224721290	288742189
	AD 1 Hippo	9.3	14.1
	AD 2 Hippo	22.2	20.2
	AD 3 Hippo	10.6	9.7
	AD 4 Hippo	7.1	5.3
	AD 5 hippo	100.0	100.0
	AD 6 Hippo	36.9	42.0
	Control 2 Hippo	22.7	23.8
	Control 4 Hippo	7.7	10.2
	Control (Path) 3 Hippo	6.9	5.2
	AD 1 Temporal Ctx	15.7	18.2
	AD 2 Temporal Ctx	20.2	20.0
	AD 3 Temporal Ctx	9.9	8.0
	AD 4 Temporal Ctx	18.8	9.8
	AD 5 Inf Temporal Ctx	97.9	81.2
	AD 5 Sup Temporal Ctx	31.6	36.3
	AD 6 Inf Temporal Ctx	26.2	28.9
	AD 6 Sup Temporal Ctx	29.1	33.7
	Control 1 Temporal Ctx	9.5	5.1
	Control 2 Temporal Ctx	39.0	43.2
	Control 3 Temporal Ctx	10.1	11.4
	Control 4 Temporal Ctx	6.6	6.7
	Control (Path) 1 Temporal Ctx	32.8	35.1
	Control (Path) 2 Temporal Ctx	20.4	22.8
	Control (Path) 3 Temporal Ctx	5.7	5.3
	Control (Path) 4 Temporal Ctx	20.0	19.2
	AD 1 Occipital Ctx	7.3	18.6
	AD 2 Occipital Ctx (Missing)	0.0	0.0
	AD 3 Occipital Ctx	11.3	8.0
	AD 4 Occipital Ctx	19.8	13.4
	AD 5 Occipital Ctx	15.9	18.0
	AD 6 Occipital Ctx	53.2	54.3
	Control 1 Occipital Ctx	4.5	3.9
	Control 2 Occipital Ctx	81.8	90.8
	Control 3 Occipital Ctx	14.4	14.7
	Control 4 Occipital Ctx	6.4	6.8
	Control (Path) 1 Occipital Ctx	45.4	57.8
	Control (Path) 2 Occipital Ctx	6.1	6.1
	Control (Path) 3 Occipital Ctx	5.1	5.2
	Control (Path) 4 Occipital Ctx	12.6	12.8
	Control 1 Parietal Ctx	6.4	5.7
	Control 2 Parietal Ctx	26.4	26.4
	Control 3 Parietal Ctx	18.0	19.6
	Control (Path) 1 Parietal Ctx	56.3	70.7
	Control (Path) 2 Parietal Ctx	15.7	15.2
	Control (Path) 3 Parietal Ctx	5.5	5.1
	Control (Path) 4 Parietal Ctx	41.5	36.3

[0823]

TABLE GD
General_screening_panel_v1.4
                                 Rel.
                                 Exp. (%)
                                 Ag4554,
                                 Run
Tissue Name                      222809973
Adipose                          5.4
Melanoma* Hs688(A).T             45.1
Melanoma* Hs688(B).T             45.1
Melanoma* M14                    85.9
Melanoma* LOXIMVI                21.9
Melanoma* SK-MEL-5               69.7
Squamous cell carcinoma SCC-4    26.8
Testis Pool                      6.8
Prostate ca.* (bone met) PC-3    29.9
Prostate Pool                    6.9
Placenta                         5.7
Uterus Pool                      4.8
Ovarian ca. OVCAR-3              14.9
Ovarian ca. SK-OV-3              100.0
Ovarian ca. OVCAR-4              10.2
Ovarian ca. OVCAR-5              36.1
Ovarian ca. IGROV-1              20.3
Ovarian ca. OVCAR-8              16.0
Ovary                            15.0
Breast ca. MCF-7                 16.5
Breast ca. MDA-MB-231            51.1
Breast ca. BT 549                47.3
Breast ca. T47D                  62.0
Breast ca. MDA-N                 17.8
Breast Pool                      12.5
Trachea                          12.3
Lung                             1.2
Fetal Lung                       27.4
Lung ca. NCI-N417                8.0
Lung ca. LX-1                    52.1
Lung ca. NCI-H146                22.5
Lung ca. SHP-77                  97.9
Lung ca. A549                    25.0
Lung ca. NCI-H526                0.0
Lung ca. NCI-H23                 45.1
Lung ca. NCI-H460                15.9
Lung ca. HOP-62                  27.4
Lung ca. NCI-H522                27.9
Liver                            3.7
Fetal Liver                      12.0
Liver ca. HepG2                  28.1
Kidney Pool                      25.0
Fetal Kidney                     13.7
Renal ca. 786-0                  24.0
Renal ca. A498                   4.5
Renal ca. ACHN                   6.3
Renal ca. UO-31                  18.8
Renal ca. TK-10                  34.6
Bladder                          15.8
Gastric ca. (liver met.) NCI-N87 21.3
Gastric ca. KATO III             84.1
Colon ca. SW-948                 0.7
Colon ca. SW480                  52.5
Colon ca.* (SW480 met) SW620     27.0
Colon ca. HT29                   12.5
Colon ca. HCT-116                72.7
Colon ca. CaCo-2                 25.5
Colon cancer tissue              24.1
Colon ca. SW1116                 8.5
Colon ca. Colo-205               12.9
Colon ca. SW-48                  6.5
Colon Pool                       15.0
Small Intestine Pool             17.8
Stomach Pool                     9.0
Bone Marrow Pool                 5.0
Fetal Heart                      23.5
Heart Pool                       12.2
Lymph Node Pool                  15.1
Fetal Skeletal Muscle            4.6
Skeletal Muscle Pool             12.0
Spleen Pool                      10.7
Thymus Pool                      26.2
CNS cancer (glio/astro) U87-MG   65.1
CNS cancer (glio/astro) U-118-MG 79.0
CNS cancer (neuro; met) SK-N-AS  48.6
CNS cancer (astro) SF-539        23.3
CNS cancer (astro) SNB-75        89.5
CNS cancer (glio) SNB-19         21.8
CNS cancer (glio) SF-295         63.7
Brain (Amygdala) Pool            14.8
Brain (cerebellum)               90.8
Brain (fetal)                    30.4
Brain (Hippocampus) Pool         15.0
Cerebral Cortex Pool             29.3
Brain (Substantia nigra) Pool    31.2
Brain (Thalamus) Pool            27.7
Brain (whole)                    29.3
Spinal Cord Pool                 11.8
Adrenal Gland                    29.1
Pituitary gland Pool             24.8
Salivary Gland                   11.6
Thyroid (female)                 11.5
Pancreatic ca. CAPAN2            10.4
Pancreas Pool                    21.8

[0824]

TABLE GE
Panel 4.1D
	Rel.	Rel.
	Exp. (%)	Exp. (%)
	Ag4554,	Ag7230,
	Run	Run
Tissue Name	199319739	288211134
Secondary Th1 act	70.2	48.3
Secondary Th2 act	44.8	30.4
Secondary Tr1 act	64.2	17.8
Secondary Th1 rest	17.7	6.7
Secondary Th2 rest	22.4	6.6
Secondary Tr1 rest	17.0	6.0
Primary Th1 act	27.7	6.0
Primary Th2 act	42.3	24.8
Primary Tr1 act	39.5	31.4
Primary Th1 rest	17.2	12.2
Primary Th2 rest	11.0	10.1
Primary Tr1 rest	39.2	1.2
CD45RA CD4 lymphocyte act	39.8	18.7
CD45RO CD4 lymphocyte act	44.4	31.4
CD8 lymphocyte act	41.2	10.8
Secondary CD8 lymphocyte rest	43.5	9.9
Secondary CD8 lymphocyte act	11.2	4.4
CD4 lymphocyte none	19.2	5.0
2ry Th1/Th2/Tr1_anti-CD95 CH11	40.9	11.2
LAK cells rest	21.0	8.0
LAK cells IL-2	23.0	13.0
LAK cells IL-2 + IL-12	12.7	1.5
LAK cells IL-2 + IFN gamma	14.6	5.6
LAK cells IL-2 + IL-18	18.7	7.7
LAK cells PMA/ionomycin	23.8	14.3
NK Cells IL-2 rest	42.9	35.8
Two Way MLR 3 day	22.5	9.9
Two Way MLR 5 day	20.9	3.3
Two Way MLR 7 day	21.2	10.2
PBMC rest	12.0	6.8
PBMC PWM	19.3	5.1
PBMC PHA-L	29.9	14.4
Ramos (B cell) none	19.3	6.5
Ramos (B cell) ionomycin	21.3	13.7
B lymphocytes PWM	18.2	9.9
B lymphocytes CD40L and IL-4	26.4	25.7
EOL-1 dbcAMP	29.3	26.2
EOL-1 dbcAMP PMA/ionomycin	23.0	7.5
Dendritic cells none	28.9	17.6
Dendritic cells LPS	9.0	2.8
Dendritic cells anti-CD40	40.6	8.3
Monocytes rest	20.7	7.6
Monocytes LPS	18.2	15.7
Macrophages rest	20.0	8.2
Macrophages LPS	4.0	2.0
HUVEC none	57.8	31.9
HUVEC starved	64.2	50.0
HUVEC IL-1beta	62.9	38.4
HUVEC IFN gamma	50.3	35.1
HUVEC TNF alpha + IFN gamma	18.2	14.0
HUVEC TNF alpha + IL4	43.2	13.1
HUVEC IL-11	38.2	16.7
Lung Microvascular EC none	100.0	100.0
Lung Microvascular EC TNFalpha +	82.4	42.0
IL-1beta
Microvascular Dermal EC none	40.3	9.7
Microsvasular Dermal EC	28.3	7.1
TNFalpha + IL-1beta
Bronchial epithelium TNFalpha +	17.7	5.6
IL1beta
Small airway epithelium none	4.5	3.6
Small airway epithelium	11.4	6.6
TNFalpha + IL-1beta
Coronery artery SMC rest	24.8	14.1
Coronery artery SMC TNFalpha +	24.7	19.8
IL-1beta
Astrocytes rest	11.7	10.2
Astrocytes TNFalpha + IL-1beta	7.8	3.8
KU-812 (Basophil) rest	5.8	4.3
KU-812 (Basophil) PMA/ionomycin	7.9	5.7
CCD1106 (Keratinocytes) none	14.6	13.4
CCD1106 (Keratinocytes)	5.7	2.1
TNFalpha + IL-1beta
Liver cirrhosis	3.0	4.0
NCI-H292 none	3.4	7.5
NCI-H292 IL-4	7.1	8.0
NCI-H292 IL-9	9.7	6.6
NCI-H292 IL-13	10.7	6.3
NCI-H292 IFN gamma	3.2	1.5
HPAEC none	31.0	13.9
HPAEC TNF alpha + IL-1 beta	52.5	31.9
Lung fibroblast none	16.0	7.7
Lung fibroblast TNF alpha +	16.8	9.6
IL-1 beta
Lung fibroblast IL-4	16.3	7.6
Lung fibroblast IL-9	23.2	11.4
Lung fibroblast IL-13	13.8	7.0
Lung fibroblast IFN gamma	7.1	6.1
Dermal fibroblast CCD1070 rest	22.7	36.6
Dermal fibroblast CCD1070 TNF	63.7	59.5
alpha
Dermal fibroblast CCD1070 IL-1	29.9	19.3
beta
Dermal fibroblast IFN gamma	7.0	5.6
Dermal fibroblast IL-4	20.6	12.9
Dermal Fibroblasts rest	15.2	20.7
Neutrophils TNFa + LPS	18.4	16.0
Neutrophils rest	16.3	20.6
Colon	14.1	3.9
Lung	9.9	2.6
Thymus	39.2	7.4
Kidney	18.8	11.6

[0825]

TABLE GF
Panel 5 Islet
                                 Rel.
                                 Exp. (%)
                                 Ag4554,
                                 Run
Tissue Name                      306350410
97457_Patient-02go_adipose       5.0
97476_Patient-07sk_skeletal muscle 0.0
97477_Patient-07ut_uterus        5.4
97478_Patient-07pl_placenta      2.6
99167_Bayer Patient 1            100.0
97482_Patient-08ut_uterus        2.4
97483_Patient-08pl_placenta      1.9
97486_Patient-09sk_skeletal muscle 3.4
97487_Patient-09ut_uterus        3.4
97488_Patient-09pl_placenta      0.9
97492_Patient-10ut_uterus        5.6
97493_Patient-10pl_placenta      6.0
97495_Patient-11go_adipose       4.7
97496_Patient-11sk_skeletal muscle 3.4
97497_Patient-11ut_uterus        6.0
97498_Patient-11pl_placenta      2.0
97500_Patient-12go_adipose       8.7
97501_Patient-12sk_skeletal muscle 14.2
97502_Patient-12ut_uterus        12.3
97503_Patient-12pl_placenta      3.5
94721_Donor 2 U - A_Mesenchymal Stem Cells 21.6
94722_Donor 2 U - B_Mesenchymal Stem Cells 6.3
94723_Donor 2 U - C_Mesenchymal Stem Cells 20.2
94709_Donor 2 AM - A_adipose     20.3
94710_Donor 2 AM - B_adipose     12.8
94711_Donor 2 AM - C_adipose     9.5
94712_Donor 2 AD - A_adipose     18.0
94713_Donor 2 AD - B_adipose     34.4
94714_Donor 2 AD - C_adipose     17.3
94742_Donor 3 U - A_Mesenchymal Stem Cells 10.0
94743_Donor 3 U - B_Mesenchymal Stem Cells 9.7
94730_Donor 3 AM - A_adipose     29.1
94731_Donor 3 AM - B_adipose     47.0
94732_Donor 3 AM - C_adipose     33.9
94733_Donor 3 AD - A_adipose     46.3
94734_Donor 3 AD - B_adipose     72.7
94735_Donor 3 AD - C_adipose     13.7
77138_Liver_HepG2untreated       41.5
73556_Heart_Cardiac stromal cells (primary) 8.5
81735_Small Intestine            18.0
72409_Kidney_Proximal Convoluted Tubule 9.3
82685_Small intestine_Duodenum   20.2
90650_Adrenal_Adrenocortical adenoma 10.1
72410_Kidney_HRCE                16.8
72411_Kidney_HRE                 6.8
73139_Uterus_Uterine smooth muscle cells 19.5

[0826] CNS_neurodegeneration_v1.0 Summary: Ag4554/Ag7230 Two experiments with different probe-primer sets are in excellent agreement. This panel confirms the expression of this gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.4 for a discussion of this gene in treatment of central nervous system disorders.

[0827] General_screeningpanel_v1.4 Summary: Ag4554 Highest expression of this gene is detected in a ovarian cancer cell line (CT=25.4). 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.

[0828] 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.

[0829] 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.

[0830] Interestingly, this gene is expressed at much higher levels in fetal (CT=27.3) when compared to adult lung (CT=31.8). This observation suggests that expression of this gene can be used to distinguish fetal from adult lung. In addition, the relative overexpression of this gene in fetal tissue suggests that the protein product may enhance lung growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of lung related diseases.

[0831] Panel 4.1D Summary: Ag4554/Ag7230 Two experiments with different probe-primer sets are in excellent agreement. Highest expression of this gene is detected in lung microvascular endothelial cells (CTs=28-29). 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.

[0832] Panel 5 Islet Summary: Ag4554 Highest expression of this gene is detected in islet cells (CT=29.8). This gene shows a widespread expression pattern which correlates with the pattern seen in panel 1.4. Please see panel 1.4 for further discussion of this gene.

[0833] H. CG143787-01: Disintegrin Protease.

[0834] Expression of gene CG143787-01 was assessed using the primer-probe sets Ag6532, Ag6655 and Ag7048, described in Tables HA, HB and HC. Please note that CG143787-01 represents a full-length physical clone.

TABLE HA
Probe Name Ag6532
			Start	SEQ ID
Primers	Sequencs	Length	Position	No
Forward	5′-atcatcaccaaagataccttttatctc-3′	27	474	276
Probe	TET-5′-agaaaccaaagtgcctgctgcaagc-3′TAMRA	25	501	277
Reverse	5′-gtgttgtcattatatttgtaggaataggt-3′	29	526	278

[0835]

TABLE HB
Probe Name Ag6655
			Start	SEQ ID
Primers	Sequenes	Length	Position	No
Forward	5′-atcatcaccaaagataccttttatctc-3′	27	474	279
Probe	TET-5′-agaaaccaaagtgcctgctgcaagc-3′TAMRA	25	501	280
Reverse	5′-gtgttgtcattatatttgtaggaataggt-3′	29	526	281

[0836]

TABLE HC
Probe Name Ag7048
			Start	SEQ ID
Primers	Sequence	Length	Position	No
Forward	5′-acatcatcaccaaagatacctttta-3′	25	472	282
Probe	TET-5′-caaagtgcctgctgcaagcacctatt-3′-TAMRA	26	507	283
Reverse	5′-gttcccacacactggtgttg-3′	20	549	284

[0837] General_screening_panel_v1.6 Summary: Ag6655/Ag7048 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0838] Panel 4.1D Summary: Ag6655 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0839] I. CG144112-01: Neuropsin Precursor.

[0840] Expression of gene CG144112-01 was assessed using the primer-probe set Ag7123, described in Table IA. Please note that CG56663-01 represents a full-length physical clone.

TABLE IA
Probe Name Ag7123
			Start	SEQ ID
Primers	Sequencs	Length	Position	No
Forward	5′-gcctgggcaggaaatacac-3′	19	353	285
Probe	TET-5′-tacgcctgggagaccacagcctacag-3′TAMRA	26	325	286
Reverse	5′-tctcggggactgcacttct-3′	19	292	287

[0841] CNS_neurodegeneration_v1.0 Summary: Ag7123 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0842] Panel 4.1D Summary: Ag7123 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0843] J. CG144112-04: Kallikrein-8.

[0844] Expression of gene CG144112-04 was assessed using the primer-probe set Ag5271, described in Table JA.

TABLE JA
Probe Name Ag5271
			Start	SEQ ID
Primers	Sequence	Length	Position	No
Forward	5′-gcagggcagggcgattct-3′	18	97	288
Probe	TET-5′-cacatcctggggctcagacccctgtg-3′-TAMRA	26	153	289
Reverse	5′-ctagaatcagcccttgctgccta-3′	23	245	290

[0845] CNS_neurodegeneration_v1.0 Summary: Ag5271 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0846] Panel 4.1D Summary: Ag5271 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0847] K. CG144686-01: Mast Cell Carboxypeptidase A Precursor.

[0848] Expression of gene CG144686-01 was assessed using the primer-probe set Ag6864, described in Table KA. Results of the RTQ-PCR runs are shown in Tables KB and KC. Please note that CG144686-01 represents a full-length physical clone.

TABLE KA
Probe Name Ag6864
			Start	SEQ ID
Primers	Sequencs	Length	Position	No
Forward	5′-aaccagtgagctccgaga-3′	18	122	291
Probe	TET-5′-caaatttggttttctccttccagaatcc-3′-TAMRA	28	146	292
Reverse	5′-tctgcacgttggctttat-3′	18	177	293

[0849]

TABLE KB
General_screening_panel_v1.6
                                 Rel.
                                 Exp. (%)
                                 Ag6864,
                                 Run
Tissue Name                      278387547
Adipose                          15.0
Melanoma* Hs688(A).T             0.3
Melanoma* Hs688(B).T             0.7
Melanoma* M14                    0.0
Melanoma* LOXIMVI                0.0
Melanoma* SK-MEL-5               0.0
Squamous cell carcinoma SCC-4    0.0
Testis Pool                      7.6
Prostate ca.* (bone met) PC-3    0.0
Prostate Pool                    16.4
Placenta                         0.1
Uterus Pool                      15.8
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                            2.5
Breast ca. MCF-7                 0.0
Breast ca. MDA-MB-231            0.0
Breast ca. BT 549                0.7
Breast ca. T47D                  0.0
Breast ca. MDA-N                 0.0
Breast Pool                      0.0
Trachea                          2.5
Lung                             2.7
Fetal Lung                       5.3
Lung ca. NCI-N417                0.0
Lung ca. LX-1                    0.0
Lung ca. NCI-H146                0.0
Lung ca. SHP-77                  4.5
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                  0.9
Lung ca. NCI-H522                0.0
Liver                            0.0
Fetal Liver                      6.0
Liver ca. HepG2                  0.0
Kidney Pool                      51.4
Fetal Kidney                     1.1
Renal ca. 786-0                  0.2
Renal ca. A498                   0.0
Renal ca. ACHN                   0.0
Renal ca. UO-31                  0.2
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                  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              70.7
Colon ca. SW1116                 0.0
Colon ca. Colo-205               0.0
Colon ca. SW-48                  0.0
Colon Pool                       78.5
Small Intestine Pool             0.0
Stomach Pool                     20.0
Bone Marrow Pool                 23.2
Fetal Heart                      4.6
Heart Pool                       20.0
Lymph Node Pool                  100.0
Fetal Skeletal Muscle            5.5
Skeletal Muscle Pool             1.5
Spleen Pool                      3.0
Thymus Pool                      18.2
CNS cancer (glio/astro) U87-MG   0.0
CNS cancer (glio/astro) U-118-MG 1.8
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                    0.7
Pituitary gland Pool             1.0
Salivary Gland                   0.0
Thyroid (female)                 0.2
Pancreatic ca. CAPAN2            0.0
Pancreas Pool                    10.4

[0850]

TABLE KC
Panel 5 Islet
	Rel.	Rel.
	Exp. (%)	Exp. (%)
	Ag6864	Ag6864,
	Run	Run
Tissue Name	305424858	307650498
97457_Patient-02go_adipose	5.5	34.9
97476_Patient-07sk_skeletal muscle	0.0	0.0
97477_Patient-07ut_uterus	1.4	32.1
97478_Patient-07pl_placenta	0.0	4.7
99167_Bayer Patient 1	0.0	0.0
97482_Patient-08ut_uterus	0.0	0.0
97483_Patient-08pl_placenta	0.0	0.0
97486_Patient-09sk_skeletal muscle	7.6	15.5
97487_Patient-09ut_uterus	28.7	11.2
97488_Patient-09pl_placenta	1.4	0.0
97492_Patient-10ut_uterus	10.4	7.2
97493_Patient-10pl_placenta	0.0	5.9
97495_Patient-11go_adipose	20.0	5.0
97496_Patient-11sk_skeletal muscle	6.0	8.7
97497_Patient-11ut_uterus	45.1	65.1
97498_Patient-11pl_placenta	0.0	0.0
97500_Patient-12go_adipose	59.9	59.9
97501_Patient-12sk_skeletal muscle	100.0	100.0
97502_Patient-12ut_uterus	29.1	97.3
97503_Patient-12pl_placenta	5.0	2.3
94721_Donor 2 U - A_Mesenchymal Stem	0.0	0.0
Cells
94722_Donor 2 U - B_Mesenchymal Stem	0.0	0.0
Cells
94723_Donor 2 U - C_Mesenchymal Stem	1.5	0.0
Cells
94709_Donor 2 AM - A_adipose	0.0	0.0
94710_Donor 2 AM - B_adipose	0.0	0.0
94711_Donor 2 AM - C_adipose	0.0	0.0
94712_Donor 2 AD - A_adipose	0.0	0.0
94713_Donor 2 AD - B_adipose	0.0	0.0
94714_Donor 2 AD - C_adipose	2.3	0.0
94742_Donor 3 U - A_Mesenchymal Stem	0.0	0.0
Cells
94743_Donor 3 U - B_Mesenchymal Stem	0.0	0.0
Cells
94730_Donor 3 AM - A_adipose	0.0	0.0
94731_Donor 3 AM - B_adipose	0.0	1.9
94732_Donor 3 AM - C_adipose	0.0	0.0
94733_Donor 3 AD - A_adipose	0.0	0.0
94734_Donor 3 AD - B_adipose	0.0	0.0
94735_Donor 3 AD - C_adipose	0.0	0.0
77138_Liver_HepG2untreated	0.0	0.0
73556_Heart_Cardiac stromal cells	5.1	3.2
(primary)
81735_Small Intestine	73.2	65.1
72409_Kidney_Proximal Convoluted	0.0	0.0
Tubule
82685_Small intestine_Duodenum	59.0	67.4
90650_Adrenal_Adrenocortical adenoma	0.0	0.0
72410_Kidney_HRCE	0.0	0.0
72411_Kidney_HRE	0.0	0.0
73139_Uterus_Uterine smooth muscle	0.0	0.0
cells

[0851] General_screening_panel_v1.6 Summary: Ag6864 Highest expression of this gene is seen in lymph node (CT=29). Moderate levels of expression are also seen predominantly in normal tissue, including adipose, colon, heart, thymus, prostate, and kidney, as well as in colon cancer tissue. Thus, expression of this gene could be used to identify these samples and tissues. Modulation of the expression of this gene may also be effective in the treatment of diseases of these tissues, including cancer, obesity and diabetes.

[0852] Panel 5 Islet Summary: Ag6864 Two experiments with the same probe and primer produce results that are in excellent agreement. Highest expression of this gene is seen in skeletal muscle (CTs=33.5). Please see Panel 1.6 for discussion of this gene.

[0853] L. CG144906-01: Testisin Precursor.

[0854] Expression of gene CG144906-01 was assessed using the primer-probe set Ag6915, described in Table LA. Please note that CG144906-01 represents a full-length physical clone.

TABLE LA
Probe Name AG6915
			Start	SEQ ID
Primers	Sequence	Length	Position	No
Forward	5′-catgccatcctccacattt-3′	19	337	294
Probe	TET-5′-cagcagtctgtccggttctcaaactc-3′-TAMRA	26	356	295
Reverse	5′-gtgcctcatcctctttgatgta-3′	22	398	296

[0855] General_screening_panel_v1.6 Summary: Ag6915 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0856] M. CG144997-01: RNase H I.

[0857] Expression of gene CG144997-01 was assessed using the primer-probe set Ag7057, described in Table MA. Results of the RTQ-PCR runs are shown in Table MB. Please note that CG144997-01 represents a full-length physical clone.

TABLE MA
Probe Name Ag7057
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-gtaaacgccgattcctgct-3′	19	468	297
Probe	TET-5′-cttctacgcccattactggagcagca-3′-TAMRA	26	493	298
Reverse	5′-gaatgagtgcagagacacgttt-3′	22	558	299

[0858]

TABLE MB
General_screening_panel_v1.6
                                 Rel.
                                 Exp. (%)
                                 Ag7057,
                                 Run
Tissue Name                      282273884
Adipose                          3.9
Melanoma* Hs688(A).T             23.8
Melanoma* Hs688(B).T             28.3
Melanoma* M14                    50.7
Melanoma* LOXIMVI                57.8
Melanoma* SK-MEL-5               51.4
Squamous cell carcinoma SCC-4    22.5
Testis Pool                      9.0
Prostate ca.* (bone met) PC-3    60.3
Prostate Pool                    5.4
Placenta                         4.5
Uterus Pool                      1.9
Ovarian ca. OVCAR-3              31.2
Ovarian ca. SK-OV-3              31.4
Ovarian ca. OVCAR-4              17.1
Ovarian ca. OVCAR-5              39.0
Ovarian ca. IGROV-1              13.3
Ovarian ca. OVCAR-8              15.0
Ovary                            4.9
Breast ca. MCF-7                 21.8
Breast ca. MDA-MB-231            17.3
Breast ca. BT 549                24.8
Breast ca. T47D                  9.5
Breast ca. MDA-N                 22.7
Breast Pool                      12.3
Trachea                          7.3
Lung                             1.9
Fetal Lung                       8.6
Lung ca. NCI-N417                10.1
Lung ca. LX-1                    22.4
Lung ca. NCI-H146                11.9
Lung ca. SHP-77                  82.9
Lung ca. A549                    54.0
Lung ca. NCI-H526                8.9
Lung ca. NCI-H23                 37.9
Lung ca. NCI-H460                37.1
Lung ca. HOP-62                  12.1
Lung ca. NCI-H522                56.6
Liver                            0.8
Fetal Liver                      6.7
Liver ca. HepG2                  18.6
Kidney Pool                      10.8
Fetal Kidney                     5.8
Renal ca. 786-0                  21.6
Renal ca. A498                   17.1
Renal ca. ACHN                   17.6
Renal ca. UO-31                  18.0
Renal ca. TK-10                  33.9
Bladder                          15.7
Gastric ca. (liver met.) NCI-N87 49.0
Gastric ca. KATO III             100.0
Colon ca. SW-948                 11.4
Colon ca. SW480                  76.3
Colon ca.* (SW480 met) SW620     34.9
Colon ca. HT29                   15.8
Colon ca. HCT-116                36.6
Colon ca. CaCo-2                 42.0
Colon cancer tissue              17.6
Colon ca. SW1116                 5.4
Colon ca. Colo-205               10.4
Colon ca. SW-48                  6.8
Colon Pool                       9.5
Small Intestine Pool             5.7
Stomach Pool                     5.1
Bone Marrow Pool                 3.3
Fetal Heart                      4.7
Heart Pool                       4.5
Lymph Node Pool                  8.9
Fetal Skeletal Muscle            4.0
Skeletal Muscle Pool             2.3
Spleen Pool                      4.1
Thymus Pool                      8.2
CNS cancer (glio/astro) U87-MG   55.5
CNS cancer (glio/astro) U-118-MG 49.7
CNS cancer (neuro; met) SK-N-AS  49.7
CNS cancer (astro) SF-539        22.1
CNS cancer (astro) SNB-75        45.1
CNS cancer (glio) SNB-19         16.7
CNS cancer (glio) SF-295         56.6
Brain (Amygdala) Pool            7.3
Brain (cerebellum)               20.0
Brain (fetal)                    8.0
Brain (Hippocampus) Pool         8.1
Cerebral Cortex Pool             12.0
Brain (Substantia nigra) Pool    6.7
Brain (Thalamus) Pool            12.1
Brain (whole)                    7.1
Spinal Cord Pool                 6.7
Adrenal Gland                    6.9
Pituitary gland Pool             2.9
Salivary Gland                   2.6
Thyroid (female)                 2.5
Pancreatic ca. CAPAN2            23.3
Pancreas Pool                    6.0

[0859] General_screening_panel_v1.6 Summary: Ag7057 Highest expression of this gene is detected in a gastric cancer cell line (CT=27). 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.

[0860] 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.

[0861] 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.

[0862] N. CG145494-01: Prestin.

[0863] Expression of gene CG145494-01 was assessed using the primer-probe sets Ag6694, Ag7803 and Ag7797, described in Tables NA, NB and NC. Results of the RTQ-PCR runs are shown in Table ND.

TABLE NA
Probe Name Ag6694
			Start	SEQ ID
Primers	Sequeces	Length	Position	No
Forward	5′-ggcacagaggccagagat-3′	18	559	300
Probe	TET-5′-gtgaccttactttcaggaatcattcagttttgc-3′-TAMRA	33	604	301
Reverse	5′-ggctctgtgaqatatatggcc-3′	21	663	302

[0864]

TABLE NB
Probe Name Ag7803
			Start	SEQ ID
Primers	Sequencs	Length	Position	No
Forward	5′-ggagaaccagcaaaatagagct-3′	22	1367	303
Probe	TET-5′-ccaatcccaggaacaaggaggacacaa-3′-TAMRA	27	1409	304
Reverse	5′-atcacagcagtgatcaaacca-3′	21	1440	305

[0865]

TABLE NC
Probe Name Ag7797
			Start	SEQ ID
Primers	Sequenes	Length	Position	No
Forward	5′-ccatctggcttaccacttttg-3′	21	1391	306
Probe	TET-5′-cacagcagtgatcaaaccatagtccaatcc-3′-TAMRA	30	1429	307
Reverse	5′-aaatcacagtcagcagagcaat-3′	22	1462	308

[0866]

TABLE ND
General_screening_panel_v1.6
                                 Rel.
                                 Exp. (%)
                                 Ag6694,
                                 Run
Tissue Name                      277223811
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    100.0
Prostate Pool                    0.9
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                          1.0
Lung                             0.0
Fetal Lung                       2.9
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                  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)               14.6
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                    0.0

[0867] CNS_neurodegeneration_v1.0 Summary: Ag7797 Expression of this gene is low/undetectable (CTs>34.7) across all of the samples on this panel.

[0868] General_screening_panel_v1.6 Summary: Ag6694 Moderate level of expression of this gene is restricted to prostate cancer cell line (CT=32.6). Therefore, expression of this gene may be used to distinguish this sample from other samples in this panel and also as diagnostic marker to detect the presence of prostate cancer. In addition, therapeutic modulation of this gene may be useful in the treatment of prostate cancer.

[0869] Panel 4.1D Summary: Ag7803 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0870] O. CG145722-01: WEE1-Like Protein Kinase.

[0871] Expression of gene CG145722-01 was assessed using the primer-probe set Ag6231, described in Table OA. Results of the RTQ-PCR runs are shown in Table OB.

TABLE OA
Probe Name Ag6231
			Start	SEQ ID
Primers	Sequence	Length	Position	NO
Forward	5′-gcttcctggctaatgagatttt-3′	22	1339	309
Probe	TET-5′-agaggattaccggcaccttcccaaag3′-TAMRA	26	1364	310
Reverse	5′-tgttaatcccaaggcaaatatg-3′	22	1394	311

[0872]

TABLE OB
General_screening_panel_v1.5
                                 Rel.
                                 Exp. (%)
                                 Ag6231,
                                 Run
Tissue Name                      259211049
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                100.0
Lung ca. SHP-77                  2.3
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                      1.8
Fetal Kidney                     2.2
Renal ca. 786-0                  0.0
Renal ca. A498                   0.0
Renal ca. ACHN                   0.0
Renal ca. UO-31                  6.0
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                  0.0
Colon ca.* (SW480 met) SW620     0.0
Colon ca. HT29                   0.0
Colon ca. HCT-116                0.0
Colon ca. CaCo-2                 97.3
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        4.2
CNS cancer (glio) SNB-19         0.0
CNS cancer (glio) SF-295         0.0
Brain (Amygdala) Pool            2.3
Brain (cerebellum)               5.6
Brain (fetal)                    2.6
Brain (Hippocampus) Pool         0.0
Cerebral Cortex Pool             0.0
Brain (Substantia nigra) Pool    0.0
Brain (Thalamus) Pool            0.0
Brain (whole)                    3.7
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            4.6
Pancreas Pool                    0.0

[0873] CNS_neurodegeneration_v1.0 Summary: Ag6231 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0874] General_screening_panel_v1.5 Summary: Ag6231 Low levels of expression of this gene is restricted to a lung cancer and a colon cancer cell lines (CTs=32.2). Therefore, expression of this gene may be used to distinguish these cell lines from other samples in this panel and also as diagnostic marker to detect the presence of colon and lung cancers. In addition, therapeutic modulation of this gene may be useful in the treatment of these cancers.

[0875] Panel 4.1D Summary: Ag6231 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0876] P. CG145754-02: Kallikrein 7 Precursor.

[0877] Expression of gene CG145754-02 was assessed using the primer-probe set Ag7038, described in Table PA. Results of the RTQ-PCR runs are shown in Tables PB and PC. Please note that CG145754-02 represents a full-length physical clone.

TABLE PA
Probe Name Ag7038
			Start	SEQ ID
Primers	Sequence	Length	Position	No
Forward	5′-tgttaatgacctcaagctcatctc-3′	24	342	312
Probe	TET-5′-ccccaggactgcacgaaggtttacaa-3′-TAMRA	26	367	313
Reverse	5′-tttcttggagtcggggatg-3′	19	426	314

[0878]

TABLE PB
General_screening_panel_v1.6
                                 Rel.
                                 Exp. (%)
                                 Ag7038,
                                 Run
Tissue Name                      282273672
Adipose                          1.6
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    3.0
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              4.1
Ovarian ca. SK-OV-3              0.0
Ovarian ca. OVCAR-4              3.1
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                    0.5
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                 4.2
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                     1.3
Renal ca. 786-0                  0.0
Renal ca. A498                   0.6
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 100.0
Gastric ca. KATO III             22.1
Colon ca. SW-948                 4.4
Colon ca. SW480                  10.5
Colon ca.* (SW480 met) SW620     0.0
Colon ca. HT29                   0.0
Colon ca. HCT-116                9.7
Colon ca. CaCo-2                 0.0
Colon cancer tissue              0.6
Colon ca. SW1116                 38.7
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        2.0
CNS cancer (glio) SNB-19         0.0
CNS cancer (glio) SF-295         0.0
Brain (Amygdala) Pool            1.5
Brain (cerebellum)               5.6
Brain (fetal)                    0.0
Brain (Hippocampus) Pool         4.0
Cerebral Cortex Pool             3.1
Brain (Substantia nigra) Pool    1.4
Brain (Thalamus) Pool            3.9
Brain (whole)                    0.2
Spinal Cord Pool                 0.3
Adrenal Gland                    0.0
Pituitary gland Pool             0.0
Salivary Gland                   0.0
Thyroid (female)                 0.0
Pancreatic ca. CAPAN2            2.2
Pancreas Pool                    0.0

[0879]

TABLE PC
Panel 5 Islet
                                 Rel.
                                 Exp. (%)
                                 Ag703,
                                 Run
Tissue Name                      305424861
97457_Patient-02go_adipose       3.0
97476_Patient-07sk_skeletal muscle 0.0
97477_Patient-07ut_uterus        0.0
97478_Patient-07pl_placenta      0.0
99167_Bayer Patient 1            0.0
97482_Patient-08ut_uterus        0.0
97483_Patient-08pl_placenta      0.0
97486_Patient-09sk_skeletal muscle 0.0
97487_Patient-09ut_uterus        0.0
97488_Patient-09pl_placenta      0.0
97492_Patient-10ut_uterus        0.0
97493_Patient-10pl_placenta      0.0
97495_Patient-11go_adipose       2.7
97496_Patient-11sk_skeletal muscle 0.0
97497_Patient-11ut_uterus        0.0
97498_Patient-11pl_placenta      0.0
97500_Patient-12go_adipose       1.5
97501_Patient-12sk_skeletal muscle 0.0
97502_Patient-12ut_uterus        1.0
97503_Patient-12pl_placenta      0.0
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     100.0
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 13.0
94743_Donor 3 U - B_Mesenchymal Stem Cells 5.5
94730_Donor 3 AM - A_adipose     0.0
94731_Donor 3 AM - B_adipose     0.0
94732_Donor 3 AM - C_adipose     0.0
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) 0.0
81735_Small Intestine            0.0
72409_Kidney_Proximal Convoluted Tubule 2.4
82685_Small intestine_Duodenum   0.0
90650_Adrenal_Adrenocortical adenoma 0.0
72410_Kidney_HRCE                5.7
72411_Kidney_HRE                 10.2
73139_Uterus_Uterine smooth muscle cells 0.0

[0880] General_screening_panel_v1.6 Summary: Ag7038 Highest expression of this gene is detected in a gastric cancer NCI-N87 cell line (CT=31.3). Expression of this gene seems to be restricted to number of colon and gastric cancer cell lines. Therefore, expression of this gene may be used to distinguish colon and gastric cancer cell lines from other samples in this panel and also as a diagnostic marker to detect the presence of colon and gastric cancers. In addition, therapeutic modulation of this gene may be useful in the treatment of colon and gastric cancer.

[0881] Panel 5 Islet Summary: Ag7038 Low levels of expression of this gene is restricted to adipose tissue (CT=33). Therefore, expression of this gene may be used to distinguish this adipose sample from other samples in this panel. In addition, therapeutic modulation of this gene may be useful in the treatment of metabolic diseases such as obesity and diabetes.

[0882] Another experiment (Run 307650500) with this probe-primer set showed low/undetectable (CTs>35) across all of the samples on this panel.

[0883] Q. CG145754-03: Kallikrein-7.

[0884] Expression of gene CG145754-03 was assessed using the primer-probe set Ag5272, described in Table QA. Results of the RTQ-PCR runs are shown in Table QB.

TABLE QA
Probe Name Ag5272
			Start	SEQ ID
Primers	Sequence	Length	Position	No
Forward	5′-ggcagccaggggtgacaa-3′	18	119	315
Probe	TET-5′-cgccccatgtgcaagaggctccc-3′-TAMRA	23	149	316
Reverse	5′-cctccgcagtggagctgatt-3′	20	201	317

[0885]

TABLE QB
Panel 4.1D
                                 Rel.
                                 Exp. (%)
                                 Ag5272,
                                 Run
Tissue Name                      230500478
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        0.6
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              0.5
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 1.3
Small airway epithelium none     100.0
Small airway epithelium TNFalpha + IL-1beta 46.7
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  1.2
CCD1106 (Keratinocytes) none     14.2
CCD1106 (Keratinocytes) TNFalpha + IL-1beta 4.5
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                   0.6
NCI-H292 IFN gamma               0.0
HPAEC none                       0.0
HPAEC TNF alpha + IL-1 beta      0.0
Lung fibroblast none             0.0
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
Dermal Fibroblasts rest          0.0
Neutrophils TNFa + LPS           0.0
Neutrophils rest                 0.0
Colon                            0.0
Lung                             0.0
Thymus                           0.0
Kidney                           11.2

[0886] Panel 4.1D Summary: Ag5272 Highest expression of this gene is seen in resting small airway epithelium (CT=32). Significant expression of this gene is also seen in cytokines TNF-a and IL-1b treated small airway epithelium. Therefore, modulation of the expression or activity of the protein encoded by this transcript through the application of small molecule therapeutics may be useful in the treatment of asthma, COPD, and emphysema.

[0887] R. CG146279-01: Potassium Channel Subfamily K Member 10.

[0888] Expression of gene CG146279-01 was assessed using the primer-probe set Ag6035, described in Table RA. Results of the RTQ-PCR runs are shown in Tables RB, RC, RD and RE.

TABLE RA
Probe Name Ag6035
			Start	SEQ ID
Primers	Sequence	Length	Position	No
Forward	5′-atgaaatttccaatcgagacg-3′	21	61	318
Probe	TET-5′-ctaaagtggccgttcccgcagc-3′-TAMRA	22	107	319
Reverse	5′-ggggttgcccgttagtg-3′	17	156	320

[0889]

TABLE RB
CNS_neurodegeneration_v1.0
                               Rel.
                               Exp. (%)
                               Ag6035,
                               Run
Tissue Name                    225246892
AD 1 Hippo                     22.5
AD 2 Hippo                     25.9
AD 3 Hippo                     12.4
AD 4 Hippo                     13.5
AD 5 Hippo                     82.9
AD 6 Hippo                     74.2
Control 2 Hippo                21.5
Control 4 Hippo                19.3
Control (Path) 3 Hippo         8.2
AD 1 Temporal Ctx              24.3
AD 2 Temporal Ctx              43.8
AD 3 Temporal Ctx              4.5
AD 4 Temporal Ctx              36.6
AD 5 Inf Temporal Ctx          100.0
AD 5 Sup Temporal Ctx          62.0
AD 6 Inf Temporal Ctx          74.7
AD 6 Sup Temporal Ctx          65.1
Control 1 Temporal Ctx         5.8
Control 2 Temporal Ctx         29.5
Control 3 Temporal Ctx         22.7
Control 3 Temporal Ctx         22.7
Control (Path) 1 Temporal Ctx  74.2
Control (Path) 2 Temporal Ctx  47.0
Control (Path) 3 Temporal Ctx  9.9
Control (Path) 4 Temporal Ctx  38.2
AD 1 Occipital Ctx             22.2
AD 2 Occipital Ctx (Missing)   0.0
AD 3 Occipital Ctx             5.3
AD 4 Occipital Ctx             35.4
AD 5 Occipital Ctx             40.9
AD 6 Occipital Ctx             17.7
Control 1 Occipital Ctx        4.8
Control 2 Occipital Ctx        53.2
Control 3 Occipital Ctx        39.2
Control 4 Occipital Ctx        8.2
Control (Path) 1 Occipital Ctx 88.3
Control (Path) 2 Occipital Ctx 7.1
Control (Path) 3 Occipital Ctx 2.5
Control (Path) 4 Occipital Ctx 37.1
Control 1 Parietal Ctx         8.9
Control 2 Parietal Ctx         77.4
Control 3 Parietal Ctx         17.1
Control (Path) 1 Parietal Ctx  77.9
Control (Path) 2 Parietal Ctx  22.4
Control (Path) 3 Parietal Ctx  6.3
Control (Path) 4 Parietal Ctx  51.4

[0890]

TABLE RC
General_screening_panel_v1.5
                                 Rel. Exp. (%)
                                 Ag6035, Run
Tissue Name                      228763481
Adipose                          0.5
Melanoma* Hs688(A).T             0.0
Melanoma* Hs688(B).T             0.0
Melanoma* M14                    0.0
Melanoma* LOXIMVI                0.0
Melanoma* SK-MEL-5               0.0
Squamous cell carcinoma SCC-4    0.0
Testis Pool                      1.3
Prostate ca.* (bone met) PC-3    0.0
Prostate Pool                    4.7
Placenta                         2.0
Uterus Pool                      2.5
Ovarian ca. OVCAR-3              3.3
Ovarian ca. SK-OV-3              2.8
Ovarian ca. OVCAR-4              3.8
Ovarian ca. OVCAR-5              7.0
Ovarian ca. IGROV-1              10.4
Ovarian ca. OVCAR-8              3.1
Ovary                            1.1
Breast ca. MCF-7                 3.7
Breast ca. MDA-MB-231            6.9
Breast ca. BT 549                2.0
Breast ca. T47D                  1.1
Breast ca. MDA-N                 4.3
Breast Pool                      4.9
Trachea                          0.2
Lung                             1.1
Fetal Lung                       4.1
Lung ca. NCI-N417                3.9
Lung ca. LX-1                    30.1
Lung ca. NCI-H146                8.4
Lung ca. SHP-77                  33.4
Lung ca. A549                    15.3
Lung ca. NCI-H526                4.8
Lung ca. NCI-H23                 5.1
Lung ca. NCI-H460                7.9
Lung ca. HOP-62                  0.0
Lung ca. NCI-H522                0.0
Liver                            0.5
Fetal Liver                      2.0
Liver ca. HepG2                  7.4
Kidney Pool                      1.6
Fetal Kidney                     3.5
Renal ca. 786-0                  2.4
Renal ca. A498                   2.4
Renal ca. ACHN                   11.8
Renal ca.UO-31                   6.2
Renal ca. TK-10                  9.3
Bladder                          2.6
Gastric ca. (liver met.) NCI-N87 8.2
Gastric ca. KATO III             12.8
Colon ca. SW-948                 1.0
Colon ca. SW480                  14.8
Colon ca.* (SW480 met) SW620     29.1
Colon ca. HT29                   1.7
Colon ca. HCT-116                12.7
Colon ca. CaCo-2                 12.3
Colon cancer tissue              5.3
Colon ca. SW1116                 0.0
Colon ca. Colo-205               3.7
Colon ca. SW-48                  3.4
Colon Pool                       0.9
Small Intestine Pool             1.5
Stomach Pool                     2.1
Bone Marrow Pool                 0.5
Fetal Heart                      1.3
Heart Pool                       0.2
Lymph Node Pool                  0.9
Fetal Skeletal Muscle            1.4
Skeletal Muscle Pool             2.3
Spleen Pool                      0.6
Thymus Pool                      2.8
CNS cancer (glio/astro) U87-MG   0.0
CNS cancer (glio/astro) U-118-MG 2.8
CNS cancer (neuro; met) SK-N-AS  2.0
CNS cancer (astro) SF-539        2.2
CNS cancer (astro) SNB-75        4.6
CNS cancer (glio) SNB-19         4.4
CNS cancer (glio) SF-295         11.4
Brain (Amygdala) Pool            15.1
Brain (cerebellum)               100.0
Brain (fetal)                    92.7
Brain (Hippocampus) Pool         32.1
Cerebral Cortex Pool             21.8
Brain (Substantia nigra) Pool    18.4
Brain (Thalamus) Pool            24.8
Brain (whole)                    29.9
Spinal Cord Pool                 16.3
Adrenal Gland                    2.2
Pituitary gland Pool             3.7
Salivary Gland                   1.0
Thyroid (female)                 2.0
Pancreatic ca. CAPAN2            0.0
Pancreas Pool                    0.6

[0891]

TABLE RD
Panel 4.1D
                                 Rel. Exp. (%)
                                 Ag6035, Run
Tissue Name                      225157775
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                10.1
Two Way MLR 5 day                0.0
Two Way MLR 7 day                0.0
PBMC rest                        5.5
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                     100.0
EOL-1 dbcAMP PMA/ionomycin       36.1
Dendritic cells none             0.0
Dendritic cells LPS              0.0
Dendritic cells anti-CD40        0.0
Monocytes rest                   9.9
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                  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                  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             0.0
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
Dermal Fibroblasts rest          0.0
Neutrophils TNFa + LPS           0.0
Neutrophils rest                 0.0
Colon                            0.0
Lung                             0.0
Thymus                           8.5
Kidney                           7.7

[0892]

TABLE RE
Panel 5 Islet
	Rel. Exp. (%)	Rel. Exp. (%)
	Ag6035 Run	Ag6035, Run
Tissue Name	253578284	306414003
97457_Patient-02go_adipose	0.0	0.0
97476_Patient-07sk_skeletal	0.0	0.0
muscle
97477_Patient-07ut_uterus	0.0	0.0
97478_Patient-07pl_placenta	0.0	0.0
99167_Bayer Patient 1	100.0	100.0
97482_Patient-08ut_uterus	0.0	0.0
97483_Patient-08pl_placenta	0.0	0.0
97486_Patient-09sk_skeletal	0.0	0.0
muscle
97487_Patient-09ut_uterus	0.0	0.0
97488_Patient-09pl_placenta	0.0	0.0
97492_Patient-10ut_uterus	0.0	0.0
97493_Patient-10pl_placenta	0.0	0.0
97495_Patient-11go_adipose	0.0	0.0
97496_Patient-11sk_skeletal	0.0	0.0
muscle
97497_Patient-11ut_uterus	0.0	0.0
97498_Patient-11pl_placenta	0.0	0.0
97500_Patient-12go_adipose	0.0	0.0
97501_Patient-12sk_skeletal	0.0	0.0
muscle
97502_Patient-12ut_uterus	0.0	0.0
97503_Patient-12pl_placenta	0.0	0.0
94721_Donor 2 U - A_Mesenchymal	0.0	0.0
Stem Cells
94722_Donor 2 U - B_Mesenchymal	0.0	0.0
Stem Cells
94723_Donor 2 U - C_Mesenchymal	0.0	0.0
Stem Cells
94709_Donor2 AM - A_adipose	0.0	0.0
94710_Donor2 AM - B_adipose	0.0	0.0
94711_Donor2 AM - C_adipose	0.0	0.0
94712_Donor2 AD - A_adipose	0.0	0.0
94713_Donor2 AD - B_adipose	0.0	0.0
94714_Donor2 AD - C_adipose	0.0	0.0
94742_Donor 3 U - A_Mesenchymal	0.0	0.0
Stem Cells
94743_Donor 3 U - B_Mesenchymal	0.0	0.0
Stem Cells
94730_Donor 3 AM - A_adipose	0.0	0.0
94731_Donor 3 AM - B_adipose	0.0	0.0
94732_Donor 3 AM - C_adipose	0.0	0.0
94733_Donor 3 AD - A_adipose	0.0	0.0
94734_Donor 3 AD - B_adipose	0.0	0.0
94735_Donor 3 AD - C_adipose	0.0	0.0
77138_Liver_HepG2untreated	0.0	0.0
73556_Heart_Cardiac stromal	0.0	0.0
cells (primary)
81735_Small Intestine	0.0	0.0
72409_Kidney_Proximal Convoluted	0.0	0.0
Tubule
82685_Small intestine_Duodenum	0.0	0.0
90650_Adrenal_Adrenocortical	0.0	16.2
adenoma
72410_Kidney_HRCE	0.0	0.0
72411_Kidney_HRE	0.0	0.0
73139_Uterus_Uterine smooth	0.0	0.0
muscle cells

[0893] CNS_neurodegeneration_v1.0 Summary: Ag6035 This panel confirms the expression of this gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.5 for a discussion of this gene in treatment of central nervous system disorders.

[0894] General_screening_panel_v1.5 Summary: Ag6035 Highest expression of this gene is detected in cerebellum (CT=27). This gene codes for a splice variant of potassium channel TREK2. As reported in literature (Bang et al., 2000, J Biol Chem 275(23): 17412-9, PMID: 10747911), this gene shows expression preferentially in all the regions of brain. 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.

[0895] Moderate to low levels of expression of this gene is also seen in number of cancer cell lines derived from brain, colon, gastric, renal, lung, breast and ovarian cancer. Therefore, therapeutic modulation of this gene may be useful in the treatment of these cancers.

[0896] In addition, low levels of expression of this gene is also seen in tissues with metabolic/endocrine functions, including pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0897] Panel 4.1D Summary: Ag6035 Highest expression of this gene is detected in eosinophils (CT=32.5). Low levels of expression of this gene is also seen in PMA/ionomycin treated eosinophils. Therefore, therapeutic modulation of this gene or its protein product may useful in the treatment of hematopoietic disorders involving eosinophils, parasitic infections, autoimmune and inflammatory diseases including allergy and asthma.

[0898] Panel 5 Islet Summary: Ag6035 Two experiments with same probe-primer sets are in excellent agreement. Low levels of expression of this gene are restricted to islet cells (CTs=33-34). This gene codes for a splice variant of potassium channel TREK2. Potassium channels play an important role in insulin secretion by islet beta cells upon stimulation by glucose. Alteration in the insulin secretion pathway through the use of sulfonylureas or genetic inactivation of K(ATP) channels may lead to inappropriate insulin secretion at low glucose (Henquin JC., 2000, Diabetes 49(11):1751-60, PMID: 11078440). Therefore, therapeutic modulation of this gene or its protein product may be useful in the treatment type 2 diabetes.

[0899] S. CG146403-01: Diacylglycerol Acyltransferase 2.

[0900] Expression of gene CG146403-01 was assessed using the primer-probe set Ag6034, described in Table SA. Results of the RTQ-PCR runs are shown in Tables SB, SC and SD.

TABLE SA
Probe Name Ag6034
			Start	SEQ ID
Primers	Sequence	Length	Position	No
Forward	5′-tggggagaatgacatctttaga-3′	22	540	321
Probe	TET-5′-cttaaggcttttgccacaggctcctg-3′-TAMRA	26	562	322
Reverse	5′-agagaagcccatgagcttctt-3′	21	613	323

[0901]

TABLE SB
General_screening_panel_v1.5
                                 Rel. Exp. (%)
                                 Ag6034, Run
Tissue Name                      228763480
Adipose                          0.2
Melanoma* Hs688(A).T             0.0
Melanoma* Hs688(B).T             0.0
Melanoma* M14                    0.1
Melanoma* LOXIMVI                0.0
Melanoma* SK-MEL-5               0.2
Squamous cell carcinoma SCC-4    0.0
Testis Pool                      0.2
Prostate ca.* (bone met) PC-3    0.4
Prostate Pool                    0.0
Placenta                         0.0
Uterus Pool                      0.0
Ovarian ca. OVCAR-3              0.0
Ovarian ca. SK-OV-3              0.2
Ovarian ca. OVCAR-4              0.0
Ovarian ca. OVCAR-5              0.1
Ovarian ca. IGROV-1              0.1
Ovarian ca. OVCAR-8              0.2
Ovary                            0.0
Breast ca. MCF-7                 0.0
Breast ca. MDA-MB-231            0.0
Breast ca. BT 549                0.1
Breast ca. T47D                  0.0
Breast ca. MDA-N                 0.0
Breast Pool                      0.0
Trachea                          0.0
Lung                             0.0
Fetal Lung                       0.4
Lung ca. NCI-N417                0.1
Lung ca. LX-1                    28.1
Lung ca. NCI-H146                0.0
Lung ca. SHP-77                  0.0
Lung ca. A549                    0.7
Lung ca. NCI-H526                0.0
Lung ca. NCI-H23                 0.0
Lung ca. NCI-H460                4.2
Lung ca. HOP-62                  0.0
Lung ca. NCI-H522                0.2
Liver                            1.7
Fetal Liver                      55.9
Liver ca. HepG2                  62.9
Kidney Pool                      0.0
Fetal Kidney                     5.1
Renal ca. 786-0                  0.0
Renal ca. A498                   0.1
Renal ca. ACHN                   0.0
Renal ca. UO-31                  0.0
Renal ca. TK-10                  27.9
Bladder                          1.2
Gastric ca. (liver met.) NCI-N87 0.5
Gastric ca. KATO III             7.9
Colon ca. SW-948                 3.6
Colon ca. SW480                  12.5
Colon ca.* (SW480 met) SW620     1.9
Colon ca. HT29                   22.7
Colon ca. HCT-116                0.0
Colon ca. CaCo-2                 100.0
Colon cancer tissue              63.3
Colon ca. SW1116                 0.0
Colon ca. Colo-205               2.1
Colon ca. SW-48                  50.0
Colon Pool                       0.2
Small Intestine Pool             0.4
Stomach Pool                     0.0
Bone Marrow Pool                 0.0
Fetal Heart                      0.2
Heart Pool                       0.1
Lymph Node Pool                  0.0
Fetal Skeletal Muscle            0.1
Skeletal Muscle Pool             0.0
Spleen Pool                      0.0
Thymus Pool                      0.1
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        0.2
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)               0.1
Brain (fetal)                    0.2
Brain (Hippocampus) Pool         0.0
Cerebral Cortex Pool             0.1
Brain (Substantia nigra) Pool    0.0
Brain (Thalamus) Pool            0.0
Brain (whole)                    1.1
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                    0.0

[0902]

TABLE SC
Panel 4.1D
                                 Rel. Exp. (%)
                                 Ag6034, Run
Tissue Name                      225245213
Secondary Th1 act                0.0
Secondary Th2 act                0.0
Secondary Tr1 act                0.4
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                         0.9
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     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        0.5
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 + 0.0
IL-1beta
Bronchial epithelium TNFalpha + IL1beta 0.0
Small airway epithelium none     0.0
Small airway epithelium TNFalpha + 0.0
IL-1beta
Coronery artery SMC rest         0.0
Coronery artery SMC TNFalpha + IL-1beta 0.6
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 + 0.0
IL-1beta
Liver cirrhosis                  17.0
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             0.0
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
Dermal Fibroblasts rest          0.3
Neutrophils TNFa + LPS           4.0
Neutrophils rest                 0.0
Colon                            81.2
Lung                             4.7
Thymus                           18.0
Kidney                           100.0

[0903]

TABLE SD
Panel 5 Islet
                                 Rel. Exp. (%)
                                 Ag603, Run
Tissue Name                      256791126
97457_Patient-02go_adipose       0.0
97476_Patient-07sk_skeletal muscle 0.0
97477_Patient-07ut_uterus        0.0
97478_Patient-07pl_placenta      0.0
99167_Bayer Patient 1            0.0
97482_Patient-08ut_uterus        0.0
97483_Patient-08pl_placenta      0.0
97486_Patient-09sk_skeletal muscle 0.0
97487_Patient-09ut_uterus        0.0
97488_Patient-09pl_placenta      0.0
97492_Patient-10ut_uterus        0.0
97493_Patient-10pl_placenta      0.0
97495_Patient-11go_adipose       0.0
97496_Patient-11sk_skeletal muscle 0.0
97497_Patient-11ut_uterus        0.0
97498_Patient-11pl_placenta      0.0
97500_Patient-12go_adipose       0.0
97501_Patient-12sk_skeletal muscle 0.0
97502_Patient-12ut_uterus        0.0
97503_Patient-12pl_placenta      0.0
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 0.0
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     0.0
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       100.0
73556_Heart_Cardiac stromal cells (primary) 0.0
81735_Small Intestine            25.5
72409_Kidney_Proximal Convoluted Tubule 0.0
82685_Small intestine_Duodenum   31.2
90650_Adrenal_Adrenocortical adenoma 0.0
72410_Kidney_HRCE                0.0
72411_Kidney_HRE                 0.0
73139_Uterus_Uterine smooth muscle cells 0.0

[0904] CNS_neurodegeneration_v1.0 Summary: Ag6034 Expression of this gene is low/undetectable in all samples on this panel (CTs>35). (Data not shown.)

[0905] General_screening_panel_v1.5 Summary: Ag6034 Highest expression of this gene is seen in colon cancer (CT=26.3). High to moderate levels of expression are also seen in colon, renal, liver and lung cancer cell lines, as well as in fetal lung. This expression suggests that this gene may be involved in these cancers. Thus, expression of this gene could be used to differentiate between these samples and other samples on this panel and as a marker of these cancers. Therapeutic modulation of the expression or function of this gene may also be useful in the treatment of these cancers.

[0906] Panel 4.1D Summary: Ag6034 Expression of this gene is highest in colon and kidney (CTs=30). Thus, expression of this gene could be used as a marker of these tissues.

[0907] Panel 5 Islet Summary: Ag6034 Highest expression of this gene is seen in a liver cell line (CT=30.6). Thus, expression of this gene could be used to differentiate between this sample and other samples on this panel.

[0908] T. CG146513-01: Diacylglycerol Acyltransferase 2.

[0909] Expression of gene CG146513-01 was assessed using the primer-probe set Ag6036, described in Table TA. Results of the RTQ-PCR runs are shown in Table TB.

TABLE TA
Probe Name Ag6036
			Start	SEQ ID
Primers	Sequence	Length	Position	No
Forward	5′-tggaccctatggaagtatttcc-3′	22	326	324
Probe	TET-5′-ttcccagtacagctggtgaagactca-3′-TAMRA	26	356	325
Reverse	5′-gttgtgtttgggagaaagatca-3′	22	382	326

[0910]

TABLE TB
Panel 5 Islet
                                 Rel. Exp. (%)
                                 Ag603, Run
Tissue Name                      279370869
97457_Patient-02go_adipose       10.5
97476_Patient-07sk_skeletal muscle 0.0
97477_Patient-07ut_uterus        3.3
97478_Patient-07pl_placenta      6.0
99167_Bayer Patient 1            3.3
97482_Patient-08ut_uterus        2.6
97483_Patient-08pl_placenta      1.0
97486_Patient-09sk_skeletal muscle 8.4
97487_Patient-09ut_uterus        5.8
97488_Patient-09pl_placenta      2.2
97492_Patient-10ut_uterus        4.0
97493_Patient-10pl_placenta      3.2
97495_Patient-11go_adipose       6.0
97496_Patient-11sk_skeletal muscle 20.2
97497_Patient-11ut_uterus        8.7
97498_Patient-11pl_placenta      1.9
97500_Patient-12go_adipose       4.0
97501_Patient-12sk_skeletal muscle 22.2
97502_Patient-12ut_uterus        7.1
97503_Patient-12pl_placenta      1.3
94721_Donor 2 U - A_Mesenchymal Stem Cells 12.8
94722_Donor 2 U - B_Mesenchymal Stem Cells 6.8
94723_Donor 2 U - C_Mesenchymal Stem Cells 11.2
94709_Donor 2 AM - A_adipose     11.4
94710_Donor 2 AM - B_adipose     6.7
94711_Donor 2 AM - C_adipose     4.2
94712_Donor 2 AD - A_adipose     23.8
94713_Donor 2 AD - B_adipose     32.8
94714_Donor 2 AD - C_adipose     22.2
94742_Donor 3 U - A_Mesenchymal Stem Cells 2.6
94743_Donor 3 U - B_Mesenchymal Stem Cells 2.5
94730_Donor 3 AM - A_adipose     12.9
94731_Donor 3 AM - B_adipose     21.0
94732_Donor 3 AM - C_adipose     20.4
94733_Donor 3 AD - A_adipose     26.4
94734_Donor 3 AD - B_adipose     25.5
94735_Donor 3 AD - C_adipose     6.5
77138_Liver_HepG2untreated       41.5
73556_Heart_Cardiac stromal cells (primary) 1.6
81735_Small Intestine            10.7
72409_Kidney_Proximal Convoluted Tubule 100.0
82685_Small intestine_Duodenum   15.7
90650_Adrenal_Adrenocortical adenoma 5.0
72410_Kidney_HRCE                31.2
72411_Kidney_HRE                 9.1
73139_Uterus_Uterine smooth muscle cells 13.3

[0911] CNS_neurodegeneration_v1.0 Summary: Ag6036 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0912] General_screen_panel_v1.5 Summary: Ag6036 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0913] Panel 4.1D Summary: Ag6036 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0914] Panel 5 Islet Summary: Ag6036 Highest expression of this gene is seen in a kidney derived sample (CT=29.5). Moderate levels of expression are seen in many samples on this panel, including samples from uterus, placenta, adipose, and skeletal muscle. Thus, this gene may be involved in diseases of these tissues, including obesity and diabetes.

[0915] U. CG146522-01: Diacylglycerol Acyltransferase 2.

[0916] Expression of gene CG146522-01 was assessed using the primer-probe set Ag6037, described in Table UA. Results of the RTQ-PCR runs are shown in Table UB.

TABLE UA
Probe Name Ag6037
			Start	SEQ ID
Primers	Sequence	Length	Position	No
Forward	5′-attccaagcagcctagtcactt-3′	22	49	327
Probe	TET-5′-ttctgcagtggcctttgagctacctt-3′-TAMRA	26	85	328
Reverse	5′-cagcaggtagacgaacaagatg-3′	122	113	329

[0917]

TABLE UB
Panel 5 Islet
                                 Rel. Exp.(%)
                                 Ag6037, Run
Tissue Name                      279370870
97457_Patient-02go_adipose       0.0
97476_Patient-07sk_skeletal muscle 0.0
97477_Patient-07ut_uterus        0.0
97478_Patient-07pl_placenta      0.0
99167_Bayer Patient 1            0.9
97482_Patient-08ut_uterus        0.8
97483_Patient-08pl_placenta      0.0
97486_Patient-09sk_skeletal muscle 9.0
97487_Patient-09ut_uterus        2.2
97488_Patient-09pl_placenta      0.0
97492_Patient-10ut_uterus        0.5
97493_Patient-10pl_placenta      3.5
97495_Patient-11go_adipose       1.2
97496_Patient-11sk_skeletal muscle 39.2
97497_Patient-11ut_uterus        0.0
97498_Patient-11pl_placenta      0.0
97500_Patient-12go_adipose       1.7
97501_Patient-12sk_skeletal muscle 100.0
97502_Patient-12ut_uterus        0.0
97503_Patient-12pl_placenta      1.0
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 0.5
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 0.0
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     0.0
94733_Donor 3 AD - A_adipose     0.0
94734_Donor 3 AD - B_adipose     0.9
94735_Donor 3 AD - C_adipose     0.0
77138_Liver_HepG2untreated       0.0
73556_Heart_Cardiac stromal cells (primary) 0.0
81735_Small Intestine            1.0
72409_Kidney_Proximal Convoluted Tubule 0.0
82685_Small intestine_Duodenum   0.0
90650_Adrenal_Adrenocortical adenoma 0.0
72410_Kidney_HRCE                0.0
72411_Kidney_HRE                 0.0
73139_Uterus_Uterine smooth muscle cells 0.0

[0918] CNS neurodegeneration_v1.0 Summary: Ag6037 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0919] General_screenin_panel_v1.5 Summary: Ag6037 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0920] Panel 4.1D Summary: Ag6037 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0921] Panel 5 Islet Summary: Ag6037 Expression of this gene is limited to skeletal muscle (CTs=30-31). Thus, expression of this gene could be used to differentiate these samples from other samples on this panel and as a marker of this tissue. Furthermore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of metabolic disorders, including obesity and diabetes.

[0922] V. CG146531-01: Diacylglycerol Acyltransferase 2.

[0923] Expression of gene CG146531-01 was assessed using the primer-probe set Ag6038, described in Table VA.

TABLE VA
Probe Name Ag6038
			Start	SEQ ID
Primers	Sequence	Length	Position	No
Forward	5′-aaggtgtcacaggaagagcat-3′	21	10	330
Probe	TET-5′-agccaggtcaccatggctttcttct-3′-TAMRA	25	49	331
Reverse	5′-gccctcctggagattcagt-3′	19	78	332

[0924] CNS_neurodegeneration_v1.0 Summary: Ag6038 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0925] General_screen_panel_v1.5 Summary: Ag6038 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0926] Panel 4.1D Summary: Ag6038 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0927] Panel-5 Islet Summary: Ag6038 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0928] W. CG147274-01: Protease.

[0929] Expression of gene CG147274-01 was assessed using the primer-probe set Ag5623, described in Table WA.

TABLE WA
Probe Name Ag5623
			Start	SEQ ID
Primers	Sequence	Length	Position	No
Forward	5′-gatgtgctgccttcagaatg-3′	20	64	333
Probe	TET-5′-aatcctcccggcctccttggagt-3′-TAMRA	23	89	334
Reverse	5′-gtccttcctgggtgtcttg-3′	19	121	335

[0930] CNS_neurodegeneration_v1.0 Summary: Ag5623 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0931] General_screen_panel_v1.5 Summary: Ag5623 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0932] Panel 4.1D Summary: Ag5623 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[0933] X. CG147419-01: Glutamine: Fructose-6-Phosphate Amidotrancferase 1 Muscle.

[0934] Expression of gene CG147419-01 was assessed using the primer-probe set Ag5207, described in Table XA. Results of the RTQ-PCR runs are shown in Tables XB, XC, XD and XE.

TABLE XA
Probe Name Ag5207
			Start	SEQ ID
Primers	Sequenes	Length	Position	No
Forward	5′-gccctctgttgattggtgta-3′	20	736	336
Probe	TET-5′-cggagtgaacataaactttctactgatca-3′-TAMRA	29	756	337
Reverse	5′-ccaatctgagtcctagctgttc-3′	22	802	338

[0935]

TABLE XB
CNS_neurodegeneration_v1.0
                               Rel. Exp. (%)
                               Ag5207, Run
Tissue Name                    226559656
AD 1 Hippo                     11.3
AD 2 Hippo                     14.6
AD 3 Hippo                     0.0
AD 4 Hippo                     6.3
AD 5 hippo                     100.0
AD 6 Hippo                     29.3
Control 2 Hippo                59.0
Control 4 Hippo                0.0
Control (Path) 3 Hippo         1.8
AD 1 Temporal Ctx              12.5
AD 2 Temporal Ctx              41.5
AD 3 Temporal Ctx              2.2
AD 4 Temporal Ctx              24.1
AD 5 Inf Temporal Ctx          65.5
AD 5 SupTemporal Ctx           29.1
AD 6 Inf Temporal Ctx          26.2
AD 6 Sup Temporal Ctx          49.3
Control 1 Temporal Ctx         0.0
Control 2 Temporal Ctx         88.3
Control 3 Temporal Ctx         19.5
Control 4 Temporal Ctx         4.9
Control (Path) 1 Temporal Ctx  97.3
Control (Path) 2 Temporal Ctx  48.0
Control (Path) 3 Temporal Ctx  2.3
Control (Path) 4 Temporal Ctx  54.7
AD 1 Occipital Ctx             1.8
AD 2 Occipital Ctx (Missing)   0.0
AD 3 Occipital Ctx             1.7
AD 4 Occipital Ctx             11.5
AD 5 Occipital Ctx             21.0
AD 6 Occipital Ctx             97.9
Control 1 Occipital Ctx        0.0
Control 2 Occipital Ctx        100.0
Control 3 Occipital Ctx        13.3
Control 4 Occipital Ctx        2.2
Control (Path) 1 Occipital Ctx 100.0
Control (Path) 2 Occipital Ctx 7.2
Control (Path) 3 Occipital Ctx 0.0
Control (Path) 4 Occipital Ctx 18.9
Control 1 Parietal Ctx         2.5
Control 2 Parietal Ctx         53.2
Control 3 Parietal Ctx         21.6
Control (Path) 1 Parietal Ctx  94.6
Control (Path) 2 Parietal Ctx  16.8
Control (Path) 3 Parietal Ctx  4.0
Control (Path) 4 Parietal Ctx  50.3

[0936]

TABLE XC
General_screening_panel_v1.5
                                 Rel. Exp. (%)
                                 Ag5207, Run
Tissue Name                      228757767
Adipose                          9.9
Melanoma* Hs688(A).T             4.0
Melanoma* Hs688(B).T             12.1
Melanoma* M14                    4.1
Melanoma* LOXIMVI                0.7
Melanoma* SK-MEL-5               1.8
Squamous cell carcinoma SCC-4    0.7
Testis Pool                      2.8
Prostate ca.* (bone met) PC-3    6.3
Prostate Pool                    4.1
Placenta                         0.2
Uterus Pool                      5.6
Ovarian ca. OVCAR-3              0.2
Ovarian ca. SK-OV-3              5.9
Ovarian ca. OVCAR-4              1.2
Ovarian ca. OVCAR-5              1.6
Ovarian ca. IGROV-1              0.8
Ovarian ca. OVCAR-8              1.7
Ovary                            0.7
Breast ca. MCF-7                 0.3
Breast ca. MDA-MB-231            3.8
Breast ca. BT 549                1.3
Breast ca. T47D                  0.0
Breast ca. MDA-N                 0.2
Breast Pool                      6.4
Trachea                          1.0
Lung                             1.5
Fetal Lung                       1.2
Lung ca. NCI-N417                0.7
Lung ca. LX-1                    0.6
Lung ca. NCI-H146                0.5
Lung ca. SHP-77                  0.4
Lung ca. A549                    4.8
Lung ca. NCI-H526                0.6
Lung ca. NCI-H23                 0.2
Lung ca. NCI-H460                3.2
Lung ca. HOP-62                  4.3
Lung ca. NCI-H522                2.0
Liver                            0.1
Fetal Liver                      0.4
Liver ca. HepG2                  0.4
Kidney Pool                      14.4
Fetal Kidney                     0.2
Renal ca. 786-0                  1.2
Renal ca. A498                   1.2
Renal ca. ACHN                   1.6
Renal ca. UO-31                  1.5
Renal ca. TK-10                  2.9
Bladder                          2.2
Gastric ca. (liver met.) NCI-N87 23.2
Gastric ca. KATO III             17.4
Colon ca. SW-948                 0.4
Colon ca. SW480                  1.3
Colon ca.* (SW480 met) SW620     0.1
Colon ca. HT29                   0.3
Colon ca. HCT-116                0.2
Colon ca. CaCo-2                 1.6
Colon cancer tissue              1.3
Colon ca. SW1116                 0.0
Colon ca. Colo-205               2.6
Colon ca. SW-48                  0.8
Colon Pool                       11.3
Small Intestine Pool             4.2
Stomach Pool                     2.9
Bone Marrow Pool                 2.1
Fetal Heart                      45.7
Heart Pool                       38.2
Lymph Node Pool                  11.3
Fetal Skeletal Muscle            19.3
Skeletal Muscle Pool             100.0
Spleen Pool                      0.5
Thymus Pool                      4.0
CNS cancer (glic/astro) U87-MG   11.0
CNS cancer (glio/astro) U-118-MG 24.0
CNS cancer (neuro; met) SK-N-AS  3.4
CNS cancer (astro) SF-539        1.0
CNS cancer (astro) SNB-75        1.4
CNS cancer (glio) SNB-19         1.2
CNS cancer (glio) SF-295         18.6
Brain (Amygdala) Pool            3.7
Brain (cerebellum)               4.6
Brain (fetal)                    0.2
Brain (Hippocampus) Pool         3.1
Cerebral Cortex Pool             6.7
Brain (Substantia nigra) Pool    4.3
Brain (Thalamus) Pool            8.2
Brain (whole)                    4.4
Spinal Cord Pool                 1.2
Adrenal Gland                    2.6
Pituitary gland Pool             1.5
Salivary Gland                   0.4
Thyroid (female)                 0.4
Pancreatic ca. CAPAN2            2.8
Pancreas Pool                    6.0

[0937]

TABLE XD
Panel 4.1D
                                 Rel. Exp. (%)
                                 Ag5207, Run
Tissue Name                      229739304
Secondary Th1 act                0.0
Secondary Th2 act                4.2
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                  5.6
Primary Tr1 act                  5.6
Primary Th1 rest                 0.0
Primary Th2 rest                 0.0
Primary Tr1 rest                 0.0
CD45RA CD4 lymphocyte act        35.6
CD45RO CD4 lymphocyte act        0.0
CD8 lymphocyte act               7.8
Secondary CD8 lymphocyte rest    0.0
Secondary CD8 lymphocyte act     0.0
CD4 lymphocyte none              10.7
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          6.0
NK Cells IL-2 rest               4.8
Two Way MLR 3 day                0.0
Two Way MLR 5 day                0.0
Two Way MLR 7 day                0.0
PBMC rest                        7.0
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             5.1
Dendritic cells LPS              0.0
Dendritic cells anti-CD40        0.0
Monocytes rest                   6.6
Monocytes LPS                    0.0
Macrophages rest                 0.0
Macrophages LPS                  0.0
HUVEC none                       6.0
HUVEC starved                    29.5
HUVEC IL-1beta                   16.0
HUVEC IFN gamma                  9.6
HUVEC TNF alpha + IFN gamma      3.5
HUVEC TNF alpha + IL4            0.0
HUVEC IL-11                      5.5
Lung Microvascular EC none       7.1
Lung Microvascular EC TNFalpha + 0.0
IL-1beta
Microvascular Dermal EC none     0.0
Microsvasular Dermal EC TNFalpha + 0.0
IL-1beta
Bronchial epithelium TNFalpha +  0.0
IL1beta
Small airway epithelium none     5.8
Small airway epithelium TNFalpha 3.6
+ IL-1beta
Coronery artery SMC rest         7.4
Coronery artery SMC TNFalpha +   13.6
IL-1beta
Astrocytes rest                  0.0
Astrocytes TNFalpha + IL-1beta   12.9
KU-812 (Basophil) rest           0.0
KU-812 (Basophil) PMA/ionomycin  0.0
CCD1106 (Keratinocytes) none     18.6
CCD1106 (Keratinocytes) TNFalpha + 0.0
IL-1beta
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                       4.7
HPAEC TNF alpha + IL-1 beta      20.9
Lung fibroblast none             17.7
Lung fibroblast TNF alpha + IL-1 23.0
beta
Lung fibroblast IL-4             10.8
Lung fibroblast IL-9             11.3
Lung fibroblast IL-13            9.2
Lung fibroblast IFN gamma        33.0
Dermal fibroblast CCD1070 rest   41.8
Dermal fibroblast CCD1070 TNF alpha 100.0
Dermal fibroblast CCD1070 IL-1 beta 77.9
Dermal fibroblast IFN gamma      7.6
Dermal fibroblast IL-4           15.3
Dermal Fibroblasts rest          34.6
Neutrophils TNFa + LPS           4.8
Neutrophils rest                 0.0
Colon                            0.0
Lung                             12.3
Thymus                           0.0
Kidney                           0.0

[0938]

TABLE XE
Panel 5 Islet
                                 Rel. Exp. (%)
                                 Ag5207, Run
Tissue Name                      263594763
97457_Patient-02go_adipose       2.0
97476_Patient-07sk_skeletal muscle 3.1
97477_Patient-07ut_uterus        3.2
97478_Patient-07pl_placenta      2.0
99167_Bayer Patient 1            1.0
97482_Patient-08ut_uterus        6.7
97483_Patient-08pl_placenta      0.0
97486_Patient-09sk_skeletal muscle 27.4
97487_Patient-09ut_uterus        12.4
97488_Patient-09pl_placenta      1.3
97492_Patient-10ut_uterus        14.4
97493_Patient-10pl_placenta      2.1
97495_Patient-11go_adipose       2.0
97496_Patient-11sk_skeletal muscle 50.3
97497_Patient-11ut_uterus        7.1
97498_Patient-11pl_placenta      0.0
97500_Patient-12go_adipose       10.7
97501_Patient-12sk_skeletal muscle 100.0
97502_Patient-12ut_uterus        10.9
97503_Patient-12pl_placenta      0.0
94721_Donor 2 U - A_Mesenchymal Stem Cells 1.8
94722_Donor 2 U - B_Mesenchymal Stem Cells 1.0
94723_Donor 2 U - C_Mesenchymal Stem Cells 3.5
94709_Donor 2 AM - A_adipose     4.6
94710_Donor 2 AM - B_adipose     1.1
94711_Donor 2 AM - C_adipose     0.8
94712_Donor 2 AD - A_adipose     1.0
94713_Donor 2 AD - B_adipose     8.1
94714_Donor 2 AD - C_adipose     5.3
94742_Donor 3 U - A_Mesenchymal Stem Cells 1.2
94743_Donor 3 U - B_Mesenchymal Stem Cells 3.7
94730_Donor 3 AM - A_adipose     4.6
94731_Donor 3 AM - B_adipose     2.1
94732_Donor 3 AM - C_adipose     1.0
94733_Donor 3 AD - A_adipose     6.9
94734_Donor 3 AD - B_adipose     3.2
94735_Donor 3 AD - C_adipose     4.4
77138_Liver_HepG2untreated       3.4
73556_Heart_Cardiac stromal cells (primary) 2.2
81735_Small Intestine            7.1
72409_Kidney_Proximal Convoluted Tubule 0.0
82685_Small intestine_Duodenum   0.0
90650_Adrenal_Adrenocortical adenoma 0.0
72410_Kidney_HRCE                4.9
72411_Kidney_HRE                 0.0
73139_Uterus_Uterine smooth muscle cells 4.0

[0939] CNS_neurodegeneration_v1.0 Summary: Ag5207 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 this gene in the central nervous system.

[0940] General_screenin_panel_v1.5 Summary: Ag5207 Highest expression of this gene is seen in skeletal muscle (CT=28). Low but significant expression is also seen in pancreas, adrenal, pituitary, adipose, adult and fetal heart, and fetal skeletal muscle. This gene encodes a protein that is homologous to Glutamine:fructose-6-phosphate amidotransferase (GFAT) which catalyzes the formation of glucosamine 6-phosphate and is the first and rate-limiting enzyme of the hexosamine biosynthetic pathway. Enhanced glucose flux via the hexosamine biosynthetic pathway has been implicated in in the induction of insulin resistance. Buse et al. showed in a mouse model that glucose flux via the hexosariine pathway is selectively increased in muscle and may contribute to muscle insulin resistance in non-insulin-dependent diabetes mellitus. (Am J Physiol 1997 Jun;272(6 Pt 1):E1080-8). Thus, based on the homology of this enzyme to GFAT and the high expression in muscle, modulation of the expression or function of this gene may be useful in the treatment of type II diabetes.

[0941] This gene is widely expressed on this panel with moderate to low expression seen throughout 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.

[0942] Moderate to low levels of expression are also seen in many cancer cell lines on this panel, including gastric cancer and melanoma cell lines. Thus, modulation of this gene product may be useful in the treatment of cancer.

[0943] Panel 4.1D Summary: Ag5207 Detectable levels of expression appear to be restricted to TNF-alpha treated dermal fibroblasts (CT=33.3). This expression suggests that this gene product may be involved in skin disorders, including psoriasis.

[0944] Panel 5 Islet Summary: Ag5207 Highest expression is seen in skeletal muscle (CT=30.2), in agreement with panel 1.5. Moderate to low levels of expression are also seen in other metabolic tissues, including uterus and adipose. Please see Panel 1.5 for discussion of this gene in metabolic disease.

[0945] Y. CG148102-01: Carnitine O-Palmitoyltransferase I.

[0946] Expression of gene CG148102-01 was assessed using the primer-probe set Ag5274, described in Table YA. Results of the RTQ-PCR runs are shown in Tables YB, YC, YD and YE.

TABLE YA
Probe Name Ag5274
			Start	SEQ ID
Primers	Sequence	Length	Position	No
Forward	5′-cacttccgggacccacagt-3′	19	1732	339
Probe	TET-5′-caccaggctctgctgaaggcagcc-3′-TAMRA	24	1783	340
Reverse	5′-caaacaggtggcggtcaact-3′	20	1821	341

[0947]

TABLE YB
CNS_neurodegeneration_v1.0
                               Rel. Exp. (%)
                               Ag5274, Run
Tissue Name                    230512893
AD 1 Hippo                     19.3
AD 2 Hippo                     33.2
AD 3 Hippo                     11.7
AD 4 Hippo                     9.9
AD 5 Hippo                     95.9
AD 6 Hippo                     43.5
Control 2 Hippo                57.0
Control 4 Hippo                11.9
Control (Path) 3 Hippo         8.5
AD 1 Temporal Ctx              17.0
AD 2 Temporal Ctx              29.5
AD 3 Temporal Ctx              8.3
AD 4 Temporal Ctx              19.6
AD 5 Inf Temporal Ctx          95.9
AD 5 Sup Temporal Ctx          53.6
AD 6 Inf Temporal Ctx          29.9
AD 6 Sup Temporal Ctx          33.2
Control 1 Temporal Ctx         8.4
Control 2 Temporal Ctx         70.2
Control 3 Temporal Ctx         25.0
Control 3 Temporal Ctx         11.3
Control (Path) 1 Temporal Ctx  74.2
Control (Path) 2 Temporal Ctx  44.4
Control (Path) 3 Temporal Ctx  7.7
Control (Path) 4 Temporal Ctx  29.7
AD 1 Occipital Ctx             18.3
AD 2 Occipital Ctx (Missing)   0.0
AD 3 Occipital Ctx             7.5
AD 4 Occipital Ctx             15.1
AD 5 Occipital Ctx             66.4
AD 6 Occipital Ctx             13.1
Control 1 Occipital Ctx        3.7
Control 2 Occipital Ctx        98.6
Control 3 Occipital Ctx        27.5
Control 4 Occipital Ctx        4.5
Control (Path) 1 Occipital Ctx 100.0
Control (Path) 2 Occipital Ctx 17.1
Control (Path) 3 Occipital Ctx 3.8
Control (Path) 4 Occipital Ctx 20.0
Control 1 Parietal Ctx         10.5
Control 2 Parietal Ctx         49.3
Control 3 Parietal Ctx         19.2
Control (Path) 1 Parietal Ctx  94.6
Control (Path) 2 Parietal Ctx  25.0
Control (Path) 3 Parietal Ctx  6.0
Control (Path) 4 Parietal Ctx  50.7

[0948]

YC
General_screening_panel_v1.5
                                 Rel. Exp. (%)
                                 Ag5274, Run
Tissue Name                      230762793
Adipose                          1.2
Melanoma* Hs688(A).T             7.4
Melanoma* Hs688(B).T             13.0
Melanoma* M14                    0.1
Melanoma* LOXMVI                 0.0
Melanoma* SK-MEL-5               0.0
Squamous cell carcinoma SCC-4    1.5
Testis Pool                      2.1
Prostate ca.* (bone met) PC-3    21.8
Prostate Pool                    0.8
Placenta                         0.7
Uterus Pool                      0.7
Ovarian ca. OVCAR-3              12.2
Ovarian ca. SK-OV-3              0.2
Ovarian ca. OVCAR-4              0.1
Ovarian ca. OVCAR-5              2.8
Ovarian ca. IGROV-1              7.2
Ovarian ca. OVCAR-8              3.9
Ovary                            6.3
Breast ca. MCF-7                 0.2
Breast ca. MDA-MB-231            4.9
Breast ca. BT 549                88.3
Breast ca. T47D                  0.0
Breast ca. MDA-N                 0.0
Breast Pool                      4.9
Trachea                          1.0
Lung                             0.9
Fetal Lung                       7.2
Lung ca. NCI-N417                8.2
Lungca. LX-1                     0.5
Lung ca. NCI-H146                16.2
Lung ca. SHP-77                  53.6
Lung ca. A549                    0.0
Lung ca. NCI-H526                3.6
Lung ca. NCI-H23                 40.9
Lung ca. NCI-H460                0.6
Lung ca. HOP-62                  1.6
Lung ca. NCI-H522                57.8
Liver                            0.3
Fetal Liver                      0.9
Liver ca. HepG2                  0.0
Kidney Pool                      4.2
Fetal Kidney                     3.6
Renal ca. 786-0                  0.0
Renal ca. A498                   0.0
Renal ca. ACHN                   0.5
Renal ca. UO-31                  0.3
Renal ca. TK-10                  0.0
Bladder                          1.7
Gastric ca. (liver met.) NCI-N87 1.0
Gastric ca. KATO III             0.2
Colon ca. SW-948                 1.4
Colon ca. SW480                  0.7
Colon ca.* (SW480 met) SW620     0.0
Colon ca. HT29                   0.2
Colon ca. HCT-116                2.1
Colon ca. CaCo-2                 0.3
Colon cancer tissue              2.4
Colon ca. SW1116                 0.0
Colon ca. Colo-205               0.0
Colon ca. SW-48                  0.0
Colon Pool                       3.5
Small Intestine Pool             2.1
Stomach Pool                     1.8
Bone Marrow Pool                 0.8
Fetal Heart                      1.7
Heart Pool                       1.5
Lymph Node Pool                  5.3
Fetal Skeletal Muscle            1.0
Skeletal Muscle Pool             0.8
Spleen Pool                      3.0
Thymus Pool                      2.7
CNS cancer (glio/astro) U87-MG   27.7
CNS cancer (glio/astro) U-118-MG 27.4
CNS cancer (neuro; met) SK-N-AS  86.5
CNS cancer (astro) SF-539        0.0
CNS cancer (astro) SNB-75        0.5
CNS cancer (glio) SNB-19         7.2
CNS cancer (glio) SF-295         17.3
Brain (Amygdala) Pool            19.9
Brain (cerebellum)               100.0
Brain (fetal)                    44.8
Brain (Hippocampus) Pool         16.8
Cerebral Cortex Pool             24.0
Brain (Substantia nigra) Pool    27.4
Brain (Thalamus) Pool            34.2
Brain (whole)                    42.0
Spinal Cord Pool                 10.5
Adrenal Gland                    1.0
Pituitary gland Pool             4.9
Salivary Gland                   0.1
Thyroid (female)                 0.6
Pancreatic ca. CAPAN2            0.0
Pancreas Pool                    4.8

[0949]

TABLE YD
Panel 4.1D
                                 Rel. Exp. (%)
                                 Ag5274, Run
Tissue Name                      230472159
Secondary Th1 act                2.3
Secondary Th2 act                1.6
Secondary Tr1 act                0.0
Secondary Th1 rest               0.0
Secondary Th2 rest               2.3
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                 4.6
Primary Tr1 rest                 0.0
CD45RA CD4 lymphocyte act        7.8
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               2.5
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                         2.2
PBMC PHA-L                       10.1
Ramos (B cell) none              0.0
Ramos (B cell) ionomycin         0.0
B lymphocytes PWM                0.0
B lymphocytes CD40L and IL-4     2.2
EOL-1 dbcAMP                     9.2
EOL-1 dbcAMP PMA/ionomycin       2.7
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                       48.3
HUVEC starved                    61.1
HUVEC IL-1beta                   45.1
HUVEC IFN gamma                  92.0
HUVEC TNF alpha + IFN gamma      15.1
HUVEC TNF alpha + IL4            11.7
HUVEC IL-11                      67.8
Lung Microvascular EC none       38.2
Lung Microvascular EC TNFalpha + IL-1beta 9.2
Microvascular Dermal EC none     26.2
Microsvasular Dermal EC TNFalpha + 9.0
IL-1beta
Bronchial epithelium TNFalpha + IL1beta 0.0
Small airway epithelium none     0.0
Small airway epithelium TNFalpha + 0.0
IL-1beta
Coronery artery SMC rest         56.6
Coronery artery SMC TNFalpha + IL-1beta 66.9
Astrocytes rest                  23.2
Astrocytes TNFalpha + IL-1beta   14.8
KU-812 (Basophil) rest           0.0
KU-812 (Basophil) PMA/ionomycin  0.0
CCD1106 (Keratinocytes) none     31.9
CCD1106 (Keratinocytes) TNFalpha + 9.4
IL-1beta
Liver cirrhosis                  5.1
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               8.6
HPAEC none                       45.4
HPAEC TNF alpha + IL-1 beta      27.9
Lung fibroblast none             100.0
Lung fibroblast TNF alpha + IL-1 beta 90.8
Lung fibroblast IL-4             22.2
Lung fibroblast IL-9             47.6
Lung fibroblast IL-13            11.8
Lung fibroblast IFN gamma        61.1
Dermal fibroblast CCD1070 rest   28.7
Dermal fibroblast CCD1070 TNF alpha 23.3
Dermal fibroblast CCD1070 IL-1 beta 28.7
Dermal fibroblast IFN gamma      16.7
Dermal fibroblast IL-4           13.1
Dermal Fibroblasts rest          58.6
Neutrophils TNFa + LPS           0.0
Neutrophils rest                 0.0
Colon                            0.0
Lung                             1.7
Thymus                           0.0
Kidney                           5.5

[0950]

TABLE YE
Panel 5 Islet
                                 Rel. Exp. (%)
                                 Ag5274, Run
Tissue Name                      307720339
97457_Patient-02go_adipose       15.3
97476_Patient-07sk_skeletal muscle 0.0
97477_Patient-07ut_uterus        13.7
97478_Patient-07pl_placenta      9.0
99167_Bayer Patient 1            51.8
97482_Patient-08ut_uterus        24.3
97483_Patient-08pl_placenta      0.0
97486_Patient-09sk_skeletal muscle 0.0
97487_Patient-09ut_uterus        7.3
97488_Patient-09pl_placenta      11.9
97492_Patient-10ut_uterus        12.8
97493_Patient-10pl_placenta      5.3
97495_Patient-11go_adipose       5.3
97496_Patient-11sk_skeletal muscle 3.8
97497_Patient-11ut_uterus        20.9
97498_Patient-11pl_placenta      5.4
97500_Patient-12go_adipose       27.0
9750l_Patient-12sk_skeletal muscle 12.5
97502_Patient-12ut_uterus        10.2
97503_Patient-12pl_placenta      2.4
94721_Donor 2 U - A_Mesenchymal Stem 100.0
Cells
94722_Donor 2 U - B_Mesenchymal Stem 43.2
Cells
94723_Donor 2 U - C_Mesenchymal Stem 63.7
Cells
94709_Donor 2 AM - A_adipose     13.9
94710_Donor 2 AM - B_adipose     15.2
9471l_Donor 2 AM - C_adipose     19.8
94712_Donor 2 AD - A_adipose     58.2
94713_Donor 2 AD - B_adipose     29.7
94714_Donor 2 AD - C_adipose     34.9
94742_Donor 3 U - A_Mesenchymal Stem 62.9
Cells
94743_Donor 3 U - B_Mesenchymal Stem 39.5
Cells
94730_Donor 3 AM - A_adipose     31.4
94731_Donor 3 AM - B_adipose     35.1
94732_Donor 3 AM - C_adipose     49.3
94733_Donor 3 AD - A_adipose     28.9
94734_Donor 3 AD - B_adipose     44.8
94735_Donor 3 AD - C_adipose     17.7
77138_Liver_HepG2untreated       6.0
73556_Heart_Cardiac stromal cells 55.5
(primary)
81735_Small Intestine            39.0
72409_Kidney_Proximal Convoluted 15.2
Tubule
82685_Small intestine_Duodenum   0.0
90650_Adrenal_Adrenocortical adenoma 12.2
72410_Kidney_HRCE                0.0
72411_Kidney_HRE                 25.7
73139_Uterus_Uterine smooth muscle 97.9
cells

[0951] CNS_neurodegeneration_v1.0 Summary: Ag5274 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.

[0952] General_screen_panel_v1.5 Summary: Ag5274 Highest expression of this gene is seen in the cerebellum (CT=29.3). Moderate expression of this gene is seen throughout the brain. Thus, this gene would be useful for distinguishing brain tissue from non-neural tissue, and may be beneficial as a drug target in neurodegenerative disease, and specifically disorders that have this brain region as the site of pathology, such as autism and the ataxias. Please see Panel_CNS_neurodegeneration for further discussion of potential utility in the central nervous system.

[0953] Low but significant expression is also seen in pancreas. This gene encodes a protein with homology to carnitine palmitoyltransferase. Giannessi et al has shown that inhibition of this enzyme produces a significant reduction in serum glucose levels (J Med Chem 2001 Jul 19;44(15):2383-6). Thus, modulation of this enzyme may also be useful in the treatment of obesity and/or diabetes.

[0954] Panel 4.1D Summary: Ag5274 Highest expression of this gene is seen in untreated lung fibroblasts. Low, but significant expression is also seen in a cluster of treated and untreated lung and dermal fibroblasts. Low levels of expression are also seen in coronary artery SMCs, and HUVECs. This profile suggests that this gene could be used to differentiate between these cells and other cells samples. In addition, this gene product may be involved in inflammatory conditions of the lung and skin.

[0955] Panel 5 Islet Summary: Ag5274 Expression is limited to a sample derived from mesenchymal stem cells (CTs=34.5).

[0956] Z. CG148431-01 and CG148431-02: Aminotransferase Simolar to Serine Palmotyltransferase.

[0957] Expression of gene CG148431-01 and CG148431-02 was assessed using the primer-probe set Ag5627, described in Table ZA. Results of the RTQ-PCR runs are shown in Tables ZB, ZC, ZD and ZE. Please note that CG148431-02 represents a full-length physical clone of the CG148431-01 gene, validating the prediction of the gene sequence.

TABLE ZA
Probe Name Ag5627
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gggctcctataacttccttggt-3′	22	555	342
Probe	TET-5′-tcctcatagactcatcatacttggctgca-3′-TAMRA	39	579	343
Reverse	5′-cctgtgccatacacctctaaaa-3′	22	620	344

[0958]

TABLE ZB
CNS_neurodegeneration_v1.0
	Rel. Exp. (%)	Rel. Exp. (%)
	Ag5627, Run	Ag5627, Run
Tissue Name	246956910	264979289
AD 1 Hippo	17.4	57.0
AD 2 Hippo	67.8	4.8
AD 3 Hippo	50.0	62.4
AD 4 Hippo	19.1	30.8
AD 5 Hippo	17.0	31.2
AD 6 Hippo	100.0	86.5
Control 2 Hippo	24.1	31.6
Control 4 Hippo	50.7	70.7
Control (Path) 3 Hippo	21.0	24.3
AD 1 Temporal Ctx	43.8	65.5
AD 2 Temporal Ctx	47.6	100.0
AD 3 Temporal Ctx	11.0	23.0
AD 4 Temporal Ctx	20.4	33.9
AD 5 Inf Temporal Ctx	31.0	31.2
AD 5 Sup Temporal Ctx	51.1	63.3
AD 6 Inf Temporal Ctx	68.8	87.7
AD 6 Sup Temporal Ctx	56.3	97.3
Control 1 Temporal Ctx	7.3	4.5
Control 2 Temporal Ctx	12.9	31.6
Control 3 Temporal Ctx	7.9	15.0
Control 3 Temporal Ctx	13.8	15.6
Control (Path) 1 Temporal Ctx	30.1	46.0
Control (Path) 2 Temporal Ctx	28.7	39.5
Control (Path) 3 Temporal Ctx	6.4	8.2
Control (Path) 4 Temporal Ctx	10.3	24.0
AD 1 Occipital Ctx	11.8	26.8
AD 2 Occipital Ctx (Missing)	0.0	0.0
AD 3 Occipital Ctx	4.2	25.9
AD 4 Occipital Ctx	20.0	27.9
AD 5 Occipital Ctx	37.4	17.0
AD 6 Occipital Ctx	29.1	22.4
Control 1 Occipital Ctx	3.9	12.1
Control 2 Occipital Ctx	20.6	29.9
Control 3 Occipital Ctx	9.3	19.9
Control 4 Occipital Ctx	16.3	44.1
Control (Path) 1 Occipital Ctx	49.0	58.2
Control (Path) 2 Occipital Ctx	6.6	15.2
Control (Path) 3 Occipital Ctx	0.0	1.6
Control (Path) 4 Occipital Ctx	23.3	14.3
Control 1 Parietal Ctx	13.1	18.3
Control 2 Parietal Ctx	31.6	68.8
Control 3 Parietal Ctx	7.9	19.8
Control (Path) 1 Parietal Ctx	63.7	87.1
Control (Path) 2 Parietal Ctx	51.1	57.4
Control (Path) 3 Parietal Ctx	3.1	6.1
Control (Path) 4 Parietal Ctx	54.7	59.5

[0959]

TABLE ZC
Panel 4.1D
                                 Rel. Exp. (%)
                                 Ag5627, Run
Tissue Name                      246490777
Secondary Th1 act                0.0
Secondary Th2 act                0.4
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                  0.2
Primary Tr1 act                  0.2
Primary Th1 rest                 0.0
Primary Th2 rest                 0.0
Primary Tr1 rest                 0.0
CD45RA CD4 lymphocyte act        2.7
CD45RO CD4 lymphocyte act        6.8
CD8 lymphocyte act               0.0
Secondary CD8 lymphocyte rest    0.8
Secondary CD8 lymphocyte act     0.0
CD4 lymphocyte none              0.0
2ry Th1/Th2/Tr1_anti-CD95 CH11   0.4
LAK cells rest                   0.0
LAK cells IL-2                   0.0
LAK cells IL-2 + IL-12           0.2
LAK cells IL-2 + IFN gamma       0.0
LAK cells IL-2 + IL-18           0.0
LAK cells PMA/ionomycin          0.2
NK Cells IL-2 rest               11.8
Two Way MLR 3 day                0.4
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                       1.3
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                     3.5
EOL-1 dbcAMP PMA/ionomycin       0.0
Dendritic cells none             1.1
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                       0.7
HUVEC starved                    2.9
HUVEC IL-1beta                   0.0
HUVEC IFN gamma                  16.7
HUVEC TNF alpha + IFN gamma      0.3
HUVEC TNF alpha + IL4            0.0
HUVEC IL-11                      1.2
Lung Microvascular EC none       0.4
Lung Microvascular EC TNFalpha + IL-1beta 0.0
Microvascular Dermal EC none     0.0
Microsvasular Dermal EC TNFalpha + IL- 0.0
1beta
Bronchial epithelium TNFalpha + IL1beta 8.4
Small airway epithelium none     18.7
Small airway epithelium TNFalpha + IL- 24.3
1beta
Coronery artery SMC rest         3.3
Coronery artery SMC TNFalpha + IL-1beta 2.8
Astrocytes rest                  3.9
Astrocytes TNFalpha + IL-1beta   1.4
KU-812 (Basophil) rest           8.0
KU-812 (Basophil) PMA/ionomycin  14.2
CCD1106 (Keratinocytes) none     17.4
CCD1106 (Keratinocytes) TNFalpha + IL- 24.3
1beta
Liver cirrhosis                  13.3
NCI-H292 none                    10.2
NCI-H292 IL-4                    36.3
NCI-H292 IL-9                    21.5
NCI-H292 IL-13                   27.7
NCI-H292 IFN gamma               18.3
HPAEC none                       0.8
HPAEC TNFalpha + IL-1 beta       0.3
Lung fibroblast none             21.5
Lung fibroblast TNF alpha + IL-1 beta 2.7
Lung fibroblast IL-4             10.2
Lung fibroblast IL-9             6.2
Lung fibroblast IL-13            1.3
Lung fibroblast IFN gamma        43.5
Dermal fibroblast CCD1070 rest   0.0
Dermal fibroblast CCD1070 TNF alpha 1.1
Dermal fibroblast CCD1070 IL-1 beta 1.6
Dermal fibroblast IFN gamma      39.5
Dermal fibroblast IL-4           12.0
Dermal Fibroblasts rest          16.0
Neutrophils TNFa + LPS           0.0
Neutrophils rest                 0.0
Colon                            3.0
Lung                             4.6
Thymus                           3.5
Kidney                           100.0

[0960]

TABLE ZD
Panel 5 Islet
	Rel. Exp. (%)	Rel. Exp. (%)
	Ag5627, Run	Ag5627, Run
Tissue Name	279371483	312852505
97457_Patient-02go_adipose	0.7	1.7
97476_Patient-07sk_skeletal	0.0	0.0
muscle
97477_Patient-07ut_uterus	0.4	0.5
97478_Patient-07pl_placenta	40.3	46.0
99167_Bayer Patient 1	0.1	0.1
97482_Patient-08ut_uterus	0.2	0.2
97483_Patient-08pl_placenta	82.9	100.0
97486_Patient-09sk_skeletal	0.2	0.1
muscle
97487_Patient-09ut_uterus	0.2	0.5
97488_Patient-09pl_placenta	29.9	25.5
97492_Patient-10ut_uterus	0.3	0.4
97493_Patient-10pl_placenta	100.0	71.7
97495_Patient-11go_adipose	1.2	0.9
97496_Patient-11sk_skeletal	0.2	0.1
muscle
97497_Patient-11ut_uterus	0.5	0.8
97498_Patient-11pl_placenta	28.1	31.6
97500_Patient-12go_adipose	1.0	1.8
97501_Patient-12sk_skeletal	0.5	0.6
muscle
97502_Patient-12ut_uterus	0.3	0.4
97503_Patient-12pl_placenta	85.9	88.3
94721_Donor 2 U - A—	1.2	1.3
Mesenchymal Stem Cells
94722_Donor 2 U - B—	0.6	0.8
Mesenchymal Stem Cells
94723_Donor 2 U - C—	1.0	1.3
Mesenchymal Stem Cells
94709_Donor 2 AM - A_adipose	1.2	1.6
94710_Donor 2 AM - B_adipose	1.1	1.7
94711_Donor 2 AM - C_adipose	0.8	1.4
94712_Donor 2 AD - A_adipose	2.7	2.0
94713_Donor 2 AD - B_adipose	4.0	3.0
94714_Donor 2 AD - C_adipose	3.0	3.0
94742_Donor 3 U - A—	0.4	0.4
Mesenchymal Stem Cells
94743_Donor 3 U - B—	0.3	0.6
Mesenchymal Stem Cells
94730_Donor 3 AM - A_adipose	3.5	3.7
94731_Donor 3 AM - B_adipose	5.3	5.6
94732_Donor 3 AM - C_adipose	3.9	4.8
94733_Donor 3 AD - A_adipose	2.6	3.5
94734_Donor 3 AD - B_adipose	2.8	3.6
94735_Donor 3 AD - C_adipose	0.5	0.8
77138_Liver_HepG2untreated	39.5	43.2
73556_Heart_Cardiac stromal	0.1	0.0
cells (primary)
81735_Small Intestine	1.8	1.9
72409_Kidney_Proximal	18.2	19.1
Convoluted Tubule
82685_Small intestine—	1.3	1.1
Duodenum
90650_Adrenal—	0.6	0.4
Adrenocortical adenoma
72410_Kidney_HRCE	3.7	4.9
72411_Kidney_HRE	1.6	1.7
73139_Uterus_Uterine	1.0	0.7
smooth muscle cells

[0961]

TABLE ZE
general oncology screening panel_v_2.4
                          Rel. Exp. (%)
                          Ag5627, Run
Tissue Name               268787222
Colon cancer 1            2.8
Colon NAT 1               2.7
Colon cancer 2            7.8
Colon NAT 2               3.1
Colon cancer 3            5.7
Colon NAT 3               6.4
Colon malignant cancer 4  3.0
Colon NAT 4               2.4
Lung cancer 1             2.9
Lung NAT 1                1.1
Lung cancer 2             16.2
Lung NAT 2                2.3
Squamous cell carcinoma 3 4.8
Lung NAT 3                0.5
Metastatic melanoma 1     8.7
Melanoma 2                3.7
Melanoma 3                9.2
Metastatic melanoma 4     16.3
Metastatic melanoma 5     20.2
Bladder cancer 1          1.3
Bladder NAT 1             0.0
Bladder cancer 2          3.9
Bladder NAT 2             0.3
Bladder NAT 3             0.2
Bladder NAT 4             1.1
Prostate adenocarcinoma 1 11.8
Prostate adenocarcinoma 2 1.0
Prostate adenocarcinoma 3 8.6
Prostate adenocarcinoma 4 1.7
Prostate NAT 5            1.1
Prostate adenocarcinoma 6 2.6
Prostate adenocarcinoma 7 3.3
Prostate adenocarcinoma 8 0.6
Prostate adenocarcinoma 9 6.5
Prostate NAT 10           1.4
Kidney cancer 1           14.2
Kidney NAT 1              7.6
Kidney cancer 2           100.0
Kidney NAT 2              15.6
Kidney cancer 3           38.7
Kidney NAT 3              6.5
Kidney cancer 4           11.8
Kidney NAT 4              6.9

[0962] CNS_neurodegeneration_v1.0 Summary: Ag5627 Two experiments with same probe-primer sets are in good agreements. 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 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.

[0963] Panel 4.1D Summary: Ag5627 Highest expression of this gene is detected in kidney. Moderate to low levels of expression of this gene is also seen in activated naive and memory T cells, IL-2 treated NK cells, IFN gamma activated HUVEC cells, cytokine activated bronchial epithelial cells, astrocytes, resting and activated small airway epithelial cells, coronery artery SMC cells, basophils, keratinocytes, mucoepidermoid NCI-H292 cells, lung and dermal fibroblast, liver cirrhosis sample and normal tissues such as colon, lung, and thymus. Therefore, therapeutic modulation of this gene or its protein product through the use of small molecule drug may be useful in the treatment of autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.

[0964] Panel 5 Islet Summary: Ag5627 Two experiments with same probe and primer sets are in good agreements. Highest expression of this gene is detected in placenta of diabetic and nondiabetic patients (CTs=26.4-26.7). Moderate to high levels of expression of this gene is also seen in liver HepG2 cell line, adipose, small intestine and kidney. This gene codes for a homolog of Serine palmitoyltransferase 2. Serine palmitoyltransferase catalyzes the first, rate limiting step in de novo ceramide biosynthesis. C2-ceramide inhibits GLUT4 translocation by inhibiting Akt phosphorylation and activation in 3T3-L1 adipocytes, independently of effects on IRS-1 (Summers et al., 1998, Mol Cell Biol 18:5457-64, PMID: 9710629). Ceramide downregulates PDE3B and induces lipolysis in 3T3-L1 cells. Ceramide effects are reversed by troglitazone (Mei et al., 2002, Diabetes 51: 631-7, PMID: 11872660). Palmitate-induced insulin resistance involves elevation of de novo ceramide synthesis in C2C12 myotubes (Schrmitz-Peiffer et al., 1999, J Biol Chem 274:24202, PMID: 10446195). Therefore, inhibition of the novel serine palmitoyltransferase through the use of small molecule drug may be beneficial in the treatment of diabetes.

[0965] General oncology screening panel_v_v2.4 Summary: Ag5627 Highest expression of this gene is detected in kidney cancer (CT=27.5). Moderate to high expression of this gene is also seen in normal and cancer samples derived from colon, lung, bladder, prostate and kidney. Moderate levels of expression of this gene is also seen in melanoma and metastatic melanoma samples. Expression of this gene is strongly associated with kidney, lung and bladder cancers as compared to the corresponding normal tissues. Therefore, expression of this gene may be used as diagnostic marker for detection of these cancers and also, therapeutic modulation of this gene or its protein product may be useful in the treatment of melanoma, colon, lung, bladder, prostate and kidney cancers.

[0966] AA. CG148888-01: Galnac 4-Sulfotransferase.

[0967] Expression of gene CG148888-01 was assessed using the primer-probe set Ag6854, described in Table AAA. Results of the RTQ-PCR runs are shown in Table AAB. Please note that CG148888-01 represents a full-length physical clone.

TABLE AAA
Probe Name Ag6854
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-accccagagccgcctggt-3′	18	369	345
Probe	TET-5′-cttggcctgatgttgaactttattcctggcacc-3′-TAMRA	33	408	346
Reverse	5′-cagcctgcaggaccctacg-3′	19	458	347

[0968]

TABLE AAB
General_screening_panel_v1.6
                                 Rel. Exp. (%)
                                 Ag6854, Run
Tissue Name                      278020603
Adipose                          0.0
Melanoma* Hs688(A).T             0.0
Melanoma* Hs688(B).T             0.2
Melanoma* M14                    0.0
Melanoma* LOXIMVI                0.0
Melanoma* SK-MEL-5               0.3
Squamous cell carcinoma SCC-4    0.1
Testis Pool                      0.2
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              0.1
Ovarian ca. IGROV-1              0.0
Ovarian ca. OVCAR-8              0.0
Ovary                            0.2
Breast ca. MCF-7                 0.7
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                      0.2
Trachea                          0.3
Lung                             0.2
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                  100.0
Lung ca. A549                    0.0
Lung ca. NCI-H526                0.4
Lung ca. NCI-H23                 0.2
Lung ca. NCI-H460                0.1
Lung ca. HOP-62                  0.0
Lung ca. NCI-H522                1.4
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                          0.1
Gastric ca. (liver met.) NCI-N87 0.0
Gastric ca. KATO III             0.0
Colon ca. SW-948                 0.0
Colon ca. SW480                  0.1
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              0.1
Colon ca. SW1116                 0.0
Colon ca. Colo-205               0.0
Colon ca. SW-48                  0.0
Colon Pool                       0.2
Small Intestine Pool             0.1
Stomach Pool                     0.3
Bone Marrow Pool                 0.1
Fetal Heart                      0.3
Heart Pool                       0.0
Lymph Node Pool                  0.5
Fetal Skeletal Muscle            0.0
Skeletal Muscle Pool             0.0
Spleen Pool                      0.6
Thymus Pool                      0.5
CNS cancer (glio/astro) U87-MG   0.0
CNS cancer (glio/astro) U-118-MG 0.0
CNS cancer (neuro; met) SK-N-AS  2.2
CNS cancer (astro) SF-539        0.0
CNS cancer (astro) SNB-75        0.7
CNS cancer (glio) SNB-19         0.0
CNS cancer (glio) SF-295         0.1
Brain (Amygdala) Pool            3.7
Brain (cerebellum)               8.8
Brain (fetal)                    16.2
Brain (Hippocampus) Pool         3.6
Cerebral Cortex Pool             3.7
Brain (Substantia nigra) Pool    4.6
Brain (Thalamus) Pool            5.0
Brain (whole)                    4.5
Spinal Cord Pool                 4.7
Adrenal Gland                    0.2
Pituitary gland Pool             8.0
Salivary Gland                   0.0
Thyroid (female)                 0.2
Pancreatic ca. CAPAN2            0.1
Pancreas Pool                    0.2

[0969] General_screen_panel_v1.6 Summary: Ag6854 Highest expression of this gene is seen in a lung cancer cell line (CT=27.8). 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.

[0970] 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 neurological disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.

[0971] AB. CGI49008-01: Novel Sodium/Hydrogen Exchanger Family Member.

[0972] Expression of gene CGI49008-01 was assessed using the primer-probe set Ag5630, described in Table ABA. Results of the RTQ-PCR runs are shown in Tables ABB, ABC, ABD and ABE.

TABLE ABA
Probe Name Ag5630
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-tattttctgggtcaggctgat-3′	21	770	348
Probe	TET-5′-tctctaaactcaacatgacagacagttttg-3′-TAMRA	30	795	349
Reverse	5′-cagatattagggagccaaacg-3′	21	825	350

[0973]

TABLE ABB
CNS_neurodegeneration_v1.0
                               Rel. Exp. (%)
                               Ag5630, Run
Tissue Name                    246956911
AD 1 Hippo                     9.3
AD 2 Hippo                     31.4
AD 3 Hippo                     5.5
AD 4 Hippo                     8.4
AD 5 hippo                     62.0
AD 6 Hippo                     46.0
Control 2 Hippo                31.4
Control 4 Hippo                15.9
Control (Path) 3 Hippo         10.4
AD 1 Temporal Ctx              12.0
AD 2 Temporal Ctx              41.8
AD 3 Temporal Ctx              2.3
AD 4 Temporal Ctx              25.7
AD 5 Inf Temporal Ctx          100.0
AD 5 Sup Temporal Ctx          48.6
AD 6 Inf Temporal Ctx          36.9
AD 6 Sup Temporal Ctx          45.7
Control 1 Temporal Ctx         14.3
Control 2 Temporal Ctx         48.6
Control 3 Temporal Ctx         12.8
Control 4 Temporal Ctx         14.1
Control (Path) 1 Temporal Ctx  52.5
Control (Path) 2 Temporal Ctx  33.9
Control (Path) 3 Temporal Ctx  9.3
Control (Path) 4 Temporal Ctx  14.5
AD 1 Occipital Ctx             7.5
AD 2 Occipital Ctx (Missing)   0.0
AD 3 Occipital Ctx             4.5
AD 4 Occipital Ctx             18.9
AD 5 Occipital Ctx             13.9
AD 6 Occipital Ctx             46.3
Control 1 Occipital Ctx        3.8
Control 2 Occipital Ctx        61.6
Control 3 Occipital Ctx        6.1
Control 4 Occipital Ctx        13.2
Control (Path) 1 Occipital Ctx 62.0
Control (Path) 2 Occipital Ctx 10.5
Control (Path) 3 Occipital Ctx 8.4
Control (Path) 4 Occipital Ctx 11.8
Control 1 Parietal Ctx         10.4
Control 2 Parietal Ctx         49.0
Control 3 Parietal Ctx         20.3
Control (Path) 1 Parietal Ctx  44.1
Control (Path) 2 Parietal Ctx  22.7
Control (Path) 3 Parietal Ctx  8.2
Control (Path) 4 Parietal Ctx  35.1

[0974]

TABLE ABC
General_screening_panel_v1.5
                                 Rel. Exp. (%)
                                 Ag5630, Run
Tissue Name                      245065625
Adipose                          4.2
Melanoma* Hs688(A).T             21.9
Melanoma* Hs688(B).T             19.2
Melanoma* M14                    41.2
Melanoma* LOXIMVI                25.2
Melanoma* SK-MEL-5               20.0
Squamous cell carcinoma SCC-4    8.4
Testis Pool                      9.1
Prostate ca.* (bone met) PC-3    5.8
Prostate Pool                    3.0
Placenta                         16.7
Uterus Pool                      4.3
Ovarian ca. OVCAR-3              35.6
Ovarian ca. SK-OV-3              15.4
Ovarian ca. OVCAR-4              9.5
Ovarian ca. OVCAR-5              44.8
Ovarian ca. IGROV-l              13.9
Ovarian ca. OVCAR-8              8.0
Ovary                            3.8
Breast ca. MCF-7                 14.9
Breast ca. MDA-MB-231            25.2
Breast ca. BT 549                32.1
Breast ca. T47D                  18.7
Breast ca. MDA-N                 9.3
Breast Pool                      1.7
Trachea                          18.4
Lung                             1.7
Fetal Lung                       9.2
Lung ca. NCI-N417                4.8
Lung ca. LX-1                    24.1
Lung ca. NCI-H146                3.6
Lung ca. SHP-77                  14.0
Lung ca. A549                    35.4
Lung ca. NCI-H526                3.5
Lung ca. NCI-H23                 23.5
Lung ca. NCI-H460                6.7
Lung ca. HOP-62                  7.6
Lung ca. NCI-H522                8.5
Liver                            4.2
Fetal Liver                      15.8
Liver ca. HepG2                  5.7
Kidney Pool                      7.7
Fetal Kidney                     5.0
Renal ca. 786-0                  19.9
Renal ca. A498                   14.3
Renal ca. ACHN                   8.9
Renal ca. UO-31                  32.1
Renal ca. TK-10                  32.8
Bladder                          9.5
Gastric ca. (liver met.) NCI-N87 100.0
Gastric ca. KATO III             52.1
Colon ca. SW-948                 5.1
Colon ca. SW480                  27.2
Colon ca.* (SW480 met) SW620     22.2
Colon ca. HT29                   10.5
Colon ca. HCT-116                15.6
Colon ca. CaCo-2                 25.9
Colon cancer tissue              12.9
Colon ca. SW1116                 3.4
Colon ca. Colo-205               19.8
Colon ca. SW-48                  12.6
Colon Pool                       6.4
Small Intestine Pool             4.0
Stomach Pool                     3.7
Bone Marrow Pool                 2.9
Fetal Heart                      4.1
Heart Pool                       3.3
Lymph Node Pool                  6.8
Fetal Skeletal Muscle            2.5
Skeletal Muscle Pool             15.6
Spleen Pool                      5.4
Thymus Pool                      7.6
CNS cancer (glio/astro) U87-MG   74.2
CNS cancer (glio/astro) U-118-MG 34.4
CNS cancer (neuro; met) SK-N-AS  8.5
CNS cancer (astro) SF-539        11.9
CNS cancer (astro) SNB-75        43.2
CNS cancer (glio) SNB-19         12.9
CNS cancer (glio) SF-295         30.8
Brain (Amygdala) Pool            4.9
Brain (cerebellum)               23.7
Brain (fetal)                    6.5
Brain (Hippocampus) Pool         7.5
Cerebral Cortex Pool             5.3
Brain (Substantia nigra) Pool    4.3
Brain (Thalamus) Pool            7.4
Brain (whole)                    5.4
Spinal Cord Pool                 6.4
Adrenal Gland                    24.1
Pituitary gland Pool             3.1
Salivary Gland                   13.2
Thyroid (female)                 8.1
Pancreatic ca. CAPAN2            26.1
Pancreas Pool                    9.3

[0975]

TABLE ABD
Panel 4.1D
                                 Rel. Exp. (%)
                                 Ag5630, Run
Tissue Name                      246490808
Secondary Th1 act                52.9
Secondary Th2 act                86.5
Secondary Tr1 act                14.5
Secondary Th1 rest               2.2
Secondary Th2 rest               1.7
Secondary Tr1 rest               0.0
Primary Th1 act                  0.8
Primary Th2 act                  42.6
Primary Tr1 act                  35.4
Primary Th1 rest                 1.9
Primary Th2 rest                 3.4
Primary Tr1 rest                 0.3
CD45RA CD4 lymphocyte act        30.6
CD45RO CD4 lymphocyte act        49.3
CD8 lymphocyte act               4.6
Secondary CD8 lymphocyte rest    29.9
Secondary CD8 lymphocyte act     6.6
CD4 lymphocyte none              0.0
2ry Th1/Th2/Tr1_anti-CD95 CH11   2.5
LAK cells rest                   11.1
LAK cells IL-2                   9.7
LAK cells IL-2 + IL-12           2.3
LAK cells IL-2 + IFN gamma       17.3
LAK cells IL-2 + IL-18           9.5
LAK cells PMA/ionomycin          36.3
NK Cells IL-2 rest               17.0
Two Way MLR 3 day                9.4
Two Way MLR 5 day                1.0
Two Way MLR 7 day                7.0
PBMC rest                        0.9
PBMC PWM                         9.9
PBMC PHA-L                       8.4
Ramos (B cell) none              1.4
Ramos (B cell) ionomycin         28.5
B lymphocytes PWM                19.6
B lymphocytes CD40L and IL-4     28.1
EOL-1 dbcAMP                     3.8
EOL-1 dbcAMP PMA/ionomycin       0.4
Dendritic cells none             9.2
Dendritic cells LPS              3.2
Dendritic cells anti-CD40        3.8
Monocytes rest                   0.0
Monocytes LPS                    100.0
Macrophages rest                 6.0
Macrophages LPS                  10.6
HUVEC none                       12.6
HUVEC starved                    21.5
HUVEC IL-1beta                   21.9
HUVEC IFN gamma                  20.2
HUVEC TNF alpha + IFN gamma      6.7
HUVEC TNF alpha + IL4            4.6
HUVEC IL-11                      12.6
Lung Microvascular EC none       31.6
Lung Microvascular EC TNFalpha + IL- 9.4
1beta
Microvascular Dermal EC none     0.7
Microsvasular Dermal EC TNFalpha + IL- 7.2
1beta
Bronchial epithelium TNFalpha + IL1beta 4.2
Small airway epithelium none     4.5
Small airway epithelium TNFalpha + IL- 29.1
1beta
Coronery artery SMC rest         9.9
Coronery artery SMC TNFalpha + IL-1beta 13.3
Astrocytes rest                  2.6
Astrocytes TNFalpha + IL-1beta   4.2
KU-812 (Basophil) rest           4.9
KU-812 (Basophil) PMA/ionomycin  11.9
CCD1106 (Keratinocytes) none     28.3
CCD1106 (Keratinocytes) TNFalpha + IL- 18.6
1beta
Liver cirrhosis                  4.6
NCI-H292 none                    46.3
NCI-H292 IL-4                    46.0
NCI-H292 IL-9                    69.3
NCI-H292 IL-13                   59.0
NCI-H292 IFN gamma               33.9
HPAEC none                       12.9
HPAEC TNF alpha + IL-1 beta      70.2
Lung fibroblast none             14.2
Lung fibroblast TNF alpha + IL-1 beta 20.0
Lung fibroblast IL-4             12.4
Lung fibroblast IL-9             4.8
Lung fibroblast IL-13            2.7
Lung fibroblast IFN gamma        27.7
Dermal fibroblast CCD1070 rest   33.9
Dermal fibroblast CCD1070 TNF alpha 62.4
Dermal fibroblast CCD1070 IL-1 beta 18.3
Dermal fibroblast IFN gamma      19.3
Dermal fibroblast IL-4           37.4
Dermal Fibroblasts rest          15.8
Neutrophils TNFa + LPS           37.6
Neutrophils rest                 41.2
Colon                            1.5
Lung                             0.9
Thymus                           2.4
Kidney                           17.2

[0976]

TABLE ABE
Panel 5 Islet
                                 Rel. Exp. (%)
                                 Ag5630, Run
Tissue Name                      279370866
97457_Patient-02go_adipose       15.5
97476_Patient-07sk_skeletal muscle 0.0
97477_Patient-07ut_uterus        5.0
97478_Patient-07pl_placenta      9.3
99167_Bayer Patient 1            100.0
97482_Patient-08ut_uterus        11.0
97483_Patient-08pl_placenta      7.9
97486_Patient-09sk_skeletal muscle 9.9
97487_Patient-09ut_uterus        4.1
97488_Patient-09pl_placenta      10.3
97492_Patient-10ut_uterus        10.2
97493_Patient-10pl_placenta      20.9
97495_Patient-11go_adipose       5.8
97496_Patient-11sk_skeletal muscle 4.4
97497_Patient-11ut_uterus        13.5
97498_Patient-11pl_placenta      3.4
97500_Patient-12go_adipose       37.1
97501_Patient-12sk_skeletal muscle 20.2
97502_Patient-12ut_uterus        22.8
97503_Patient-12pl_placenta      13.1
94721_Donor 2 U - A_Mesenchymal Stem 87.7
Cells
94722_Donor 2 U - B_Mesenchymal Stem 75.8
Cells
94723_Donor 2 U - C_Mesenchymal Stem 77.9
Cells
94709_Donor 2 AM - A_adipose     26.6
94710_Donor 2 AM - B_adipose     21.0
94711_Donor 2 AM - C_adipose     16.7
94712_Donor 2 AD - A_adipose     55.9
94713_Donor 2 AD - B_adipose     74.7
94714_Donor 2 AD - C_adipose     54.7
94742_Donor 3 U - A_Mesenchymal Stem 5.7
Cells
94743_Donor 3 U - B_Mesenchymal Stem 8.0
Cells
94730_Donor 3 AM - A_adipose     8.3
94731_Donor 3 AM - B_adipose     14.3
94732_Donor 3 AM - C_adipose     11.3
94733_Donor 3 AD - A_adipose     30.1
94734_Donor 3 AD - B_adipose     22.5
94735_Donor 3 AD - C_adipose     7.5
77138_Liver_HepG2untreated       2.5
73556_Heart_Cardiac stromal cells 2.7
(primary)
81735_Small Intestine            12.6
72409_Kidney_Proximal Convoluted Tubule 28.1
82685_Small intestine_Duodenum   24.0
90650_Adrenal_Adrenocortical adenoma 7.3
72410_Kidney_HRCE                33.0
72411_Kidney_HRE                 10.4
73139_Uterus_Uterine smooth muscle 11.8
cells

[0977] CNS_neurodegeneration_v1.0 Summary: Ag5630 This panel confirms the expression of this gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.5 for a discussion of this gene in treatment of central nervous system disorders.

[0978] General_screen_panel_v1.5 Summary: Ag5630 Higest expression of this gene is detected in a gastric cancer NCI-N87 cell line (CT=27.6). 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.

[0979] 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.

[0980] 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.

[0981] Panel 4.1D Summary: Ag5630 Higest expression of this gene is detected in LPS treated monocytes (CT=29.7). Interestingly, this gene is expressed at much higher levels in LPS activated when compared to resting monocytes (CT=40). This observation suggests that expression of this gene can be used to distinguish actvated from resting monocytes. In addition, upon activation monocytes contribute to the innate and specific immunity by migrating to the site of tissue injury and releasing inflammatory cytokines. This release contributes to the inflammation process. Therefore, modulation of the expression of the protein encoded by this gene may prevent the recruitment of monocytes and the initiation of the inflammatory process.

[0982] In addition, this gene is also expressed at moderate to low levels in activated polarized T cells, naive and memory T cells, resting and activated LAK cells, resting IL-2 treated NK cells, two way MLR, activated PBMC cells and B lymphocytes, dendritic cells, macrophage, different endothelial cells, bronchial and small airway epithelium, astrocytes, basophils, keratinocytes, mucoepidermoid cells, lung and dermal fibroblasts, neutrophils and kidney. 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.

[0983] Panel 5 Islet Summary: Ag5630 Higest expression of this gene is detected in beta islet cells (CT=26.7). In addition, this gene shows widespread expression in this panel, with moderate to low expressions in adipose, placenta, uterus, skeletal muscle, kidney, and small intestine samples. Therefore, therapeutic modulation of this gene may be useful in the treatment of metabolic/endocrine disorders including, obesity, Type I and II diabetes.

[0984] AC. CG149350-01 and CG149350-02: Vacuolar ATP Synthase Subunit F.

[0985] Expression of gene CG149350-01 and CG149350-02 was assessed using the primer-probe set Ag7581, described in Table ACA. Results of the RTQ-PCR runs are shown in Table ACB. Please note that CG149350-02 represents a full-length physical clone of the CG149350-01 gene, validating the prediction of the gene sequence.

TABLE ACA
Probe Name Ag7581
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-aagaactgccaccccaatt-3′	19	88	351
Probe	TET-5′-cattgatggtcgtatccttctccacca-3′-TAMRA	27	113	352
Reverse	5′-aaattgccggaaagtgtctt-3′	20	146	353

[0986]

TABLE ACB
CNS_neurodegeneration_v1.0
                               Rel. Exp. (%)
                               Ag7581, Run
Tissue Name                    308752174
AD 1 Hippo                     19.9
AD 2 Hippo                     21.3
AD 3 Hippo                     14.9
AD 4 Hippo                     6.4
AD 5 hippo                     65.5
AD 6 Hippo                     44.4
Control 2 Hippo                21.9
Control 4 Hippo                30.6
Control (Path) 3 Hippo         10.7
AD 1 Temporal Ctx              23.0
AD 2 Temporal Ctx              27.5
AD 3 Temporal Ctx              19.8
AD 4 Temporal Ctx              21.3
AD 5 Inf Temporal Ctx          46.3
AD 5 Sup Temporal Ctx          55.9
AD 6 Inf Temporal Ctx          52.9
AD 6 Sup Temporal Ctx          47.3
Control 1 Temporal Ctx         23.5
Control 2 Temporal Ctx         28.9
Control 3 Temporal Ctx         22.2
Control 4 Temporal Ctx         9.1
Control (Path) 1 Temporal Ctx  45.7
Control (Path) 2 Temporal Ctx  62.0
Control (Path) 3 Temporal Ctx  7.3
Control (Path) 4 Temporal Ctx  62.9
AD 1 Occipital Ctx             19.1
AD 2 Occipital Ctx (Missing)   0.0
AD 3 Occipital Ctx             22.4
AD 4 Occipital Ctx             32.3
AD 5 Occipital Ctx             4.4
AD 6 Occipital Ctx             20.2
Control 1 Occipital Ctx        3.0
Control 2 Occipital Ctx        35.6
Control 3 Occipital Ctx        53.2
Control 4 Occipital Ctx        6.8
Control (Path) 1 Occipital Ctx 70.7
Control (Path) 2 Occipital Ctx 17.9
Control (Path) 3 Occipital Ctx 4.2
Control (Path) 4 Occipital Ctx 32.5
Control 1 Parietal Ctx         8.7
Control 2 Parietal Ctx         56.3
Control 3 Parietal Ctx         32.5
Control (Path) 1 Parietal Ctx  100.0
Control (Path) 2 Parietal Ctx  38.4
Control (Path) 3 Parietal Ctx  17.6
Control (Path) 4 Parietal Ctx  64.2

[0987] CNS_neurodegeneration_v1.0 Summary: Ag7581 No differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. However, this panel confirms the expression of this gene at low levels in the brains of an independent group of individuals. Therefore, therapeutic modulation of this gene product may be useful in the treatment of central nervous system disorders such as Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0988] AD. CGI49536-01: Protein-Tyrosine Phosphatase, Non-Receptor Type 2.

[0989] Expression of gene CGI49536-01 was assessed using the primer-probe sets Ag5255 and Ag6844, described in Tables ADA and ADB. Results of the RTQ-PCR runs are shown in Tables ADC, ADD and ADE.

TABLE ADA
Probe Name Ag5255
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-cttatggtttggcagcagaa-3′	20	355	354
Probe	TET-5′-ccaaagcagttgtcatgctgaaccgc-3′-TAMRA	26	377	355
Reverse	5′-tggtttcaccactcgattct-3′	20	414	356

[0990]

TABLE ADB
Probe Name Ag6844
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-agagaatcgagtggtgaaacc-3′	21	412	357
Probe	TET-5′-actacctggccagattttggagtccc-3′-TAMRA	26	457	358
Reverse	5′-aggagccagattctctcacttta-3′	23	516	359

[0991]

TABLE ADC
CNS_neurodegeneration_v1.0
                               Rel. Exp. (%)
                               Ag5255, Run
Tissue Name                    229929883
AD 1 Hippo                     28.9
AD 2 Hippo                     42.3
AD 3 Hippo                     42.0
AD 4 Hippo                     5.9
AD 5 hippo                     92.7
AD 6 Hippo                     29.7
Control 2 Hippo                52.5
Control 4 Hippo                22.4
Control (Path) 3 Hippo         17.9
AD 1 Temporal Ctx              39.5
AD 2 Temporal Ctx              56.3
AD 3 Temporal Ctx              23.3
AD 4 Temporal Ctx              10.9
AD 5 Inf Temporal Ctx          44.8
AD 5 Sup Temporal Ctx          53.2
AD 6 Inf Temporal Ctx          68.8
AD 6 Sup Temporal Ctx          100.0
Control 1 Temporal Ctx         13.4
Control 2 Temporal Ctx         34.4
Control 3 Temporal Ctx         84.1
Control 4 Temporal Ctx         18.4
Control (Path) 1 Temporal Ctx  41.2
Control (Path) 2 Temporal Ctx  58.6
Control (Path) 3 Temporal Ctx  21.0
Control (Path) 4 Temporal Ctx  38.7
AD 1 Occipital Ctx             45.4
AD 2 Occipital Ctx (Missing)   0.0
AD 3 Occipital Ctx             36.9
AD 4 Occipital Ctx             23.5
AD 5 Occipital Ctx             13.6
AD 6 Occipital Ctx             47.6
Control 1 Occipital Ctx        3.2
Control 2 Occipital Ctx        57.4
Control 3 Occipital Ctx        31.2
Control 4 Occipital Ctx        5.0
Control (Path) 1 Occipital Ctx 99.3
Control (Path) 2 Occipital Ctx 40.3
Control (Path) 3 Occipital Ctx 0.0
Control (Path) 4 Occipital Ctx 24.0
Control 1 Parietal Ctx         20.6
Control 2 Parietal Ctx         68.3
Control 3 Parietal Ctx         29.5
Control (Path) 1 Parietal Ctx  46.3
Control (Path) 2 Parietal Ctx  31.2
Control (Path) 3 Parietal Ctx  6.9
Control (Path) 4 Parietal Ctx  45.1

[0992]

TABLE ADD
General_screening_panel_v1.5
                                 Rel. Exp. (%)
                                 Ag5255, Run
Tissue Name                      230218532
Adipose                          6.4
Melanoma* Hs688(A).T             9.5
Melanoma* Hs688(B).T             8.7
Melanoma* M14                    19.1
Melanoma* LOXMVI                 25.5
Melanoma* SK-MEL-5               18.8
Squamous cell carcinoma SCC-4    24.0
Testis Pool                      2.2
Prostate ca.* (bone met) PC-3    33.9
Prostate Pool                    4.1
Placenta                         1.9
Uterus Pool                      2.3
Ovarian ca. OVCAR-3              19.6
Ovarian ca. SK-OV-3              55.5
Ovarian ca. OVCAR-4              8.5
Ovarian ca. OVCAR-5              44.4
Ovarian ca. IGROV-1              5.7
Ovarian ca. OVCAR-8              7.8
Ovary                            8.0
Breast ca. MCF-7                 38.2
Breast ca. MDA-MB-231            13.4
Breast ca. BT 549                51.8
Breast ca. T47D                  5.4
Breast ca. MDA-N                 7.0
Breast Pool                      9.0
Trachea                          1.0
Lung                             5.7
Fetal Lung                       17.1
Lung ca. NCI-N417                1.0
Lung ca. LX-1                    12.6
Lung ca. NCI-H146                16.6
Lung ca. SHP-77                  34.6
Lung ca. A549                    15.1
Lung ca. NCI-H526                6.7
Lung ca. NCI-H23                 33.0
Lung ca. NCI-H460                7.2
Lung ca. HOP-62                  26.2
Lung ca. NCI-H522                35.1
Liver                            0.9
Fetal Liver                      7.2
Liver ca. HepG2                  9.7
Kidney Pool                      7.3
Fetal Kidney                     16.3
Renal ca. 786-0                  7.1
Renal ca. A498                   2.2
Renal ca. ACHN                   9.2
Renal ca. UO-31                  6.5
Renal ca. TK-10                  18.8
Bladder                          10.8
Gastric ca. (liver met.) NCI-N87 50.3
Gastric ca. KATO III             60.3
Colon ca. SW-948                 5.8
Colon ca. SW480                  100.0
Colon ca.* (SW480 met) SW620     23.3
Colon ca. HT29                   19.2
Colon ca. HCT-116                46.7
Colon ca. CaCo-2                 49.3
Colon cancer tissue              5.7
Colon ca. SW1116                 3.5
Colon ca. Colo-205               3.3
Colon ca. SW-48                  0.5
Colon Pool                       5.9
Small Intestine Pool             5.7
Stomach Pool                     3.2
Bone Marrow Pool                 2.8
Fetal Heart                      3.7
Heart Pool                       0.7
Lymph Node Pool                  4.1
Fetal Skeletal Muscle            5.8
Skeletal Muscle Pool             2.6
Spleen Pool                      0.4
Thymus Pool                      19.2
CNS cancer (glio/astro) U87-MG   26.4
CNS cancer (glio/astro) U-118-MG 33.2
CNS cancer (neuro; met) SK-N-AS  18.9
CNS cancer (astro) SF-539        17.1
CNS cancer (astro) SNB-75        12.2
CNS cancer (glio) SNB-19         6.4
CNS cancer (glio) SF-259         16.0
Brain (Amygdala) Pool            4.0
Brain (cerebellum)               33.2
Brain (fetal)                    54.0
Brain (Hippocampus) Pool         4.7
Cerebral Cortex Pool             5.3
Brain (Substantia nigra) Pool    4.0
Brain (Thalamus) Pool            6.8
Brain (whole)                    4.9
Spinal Cord Pool                 7.0
Adrenal Gland                    2.4
Pituitary gland Pool             2.1
Salivary Gland                   1.5
Thyroid (female)                 1.1
Pancreatic ca. CAPAN2            66.4
Pancreas Pool                    7.2

[0993]

TABLE ADE
Panel 4.1D
	Rel. Exp. (%)	Rel. Exp. (%)
	Ag5255, Run	Ag6844, Run
Tissue Name	229851730	279029113
Secondary Th1 act	39.0	38.7
Secondary Th2 act	46.7	55.9
Secondary Tr1 act	15.7	18.9
Secondary Th1 rest	12.0	3.9
Secondary Th2 rest	0.0	5.3
Secondary Tr1 rest	0.0	9.2
Primary Th1 act	17.9	6.0
Primary Th2 act	15.0	33.7
Primary Tr1 act	18.2	22.7
Primary Th1 rest	0.0	1.9
Primary Th2 rest	5.0	1.5
Primary Tr1 rest	0.0	0.0
CD45RA CD4 lymphocyte act	32.1	13.9
CD45RO CD4 lymphocyte act	58.6	42.9
CD8 lymphocyte act	5.2	18.7
Secondary CD8 lymphocyte	10.9	5.5
rest
Secondary CD8 lymphocyte	0.0	4.4
act
CD4 lymphocyte none	6.7	3.4
2ry Th1/Th2/Tr1_anti-CD95	0.0	26.4
CH11
LAK cells rest	19.1	14.7
LAK cells IL-2	5.4	7.3
LAK cells IL-2 + IL-12	7.9	1.0
LAK cells IL-2 + IFN	16.2	7.7
gamma
LAK cells IL-2 + IL-18	5.1	8.0
LAK cells PMA/ionomycin	27.9	40.9
NK Cells IL-2 rest	27.9	40.3
Two Way MLR 3 day	18.2	27.0
Two Way MLR 5 day	23.3	2.1
Two Way MLR 7 day	4.5	1.7
PBMC rest	3.2	5.4
PBMC PWM	20.6	9.8
PBMC PHA-L	21.6	12.1
Ramos (B cell) none	40.3	4.8
Ramos (B cell) ionomycin	31.6	17.7
B lymphocytes PWM	26.6	6.0
B lymphocytes CD40L and	4.8	37.6
IL-4
EOL-1 dbcAMP	62.9	74.2
EOL-1 dbcAMP PMA/ionomycin	45.4	15.1
Dendritic cells none	33.7	57.0
Dendritic cells LPS	21.0	15.2
Dendritic cells anti-CD40	10.2	7.3
Monocytes rest	4.3	32.1
Monocytes LPS	69.7	100.0
Macrophages rest	17.0	3.8
Macrophages LPS	0.0	9.3
HUVEC none	5.9	28.7
HUVEC starved	28.1	8.5
HUVEC IL-1beta	39.8	9.6
HUVEC IFN gamma	12.5	15.9
HUVEC TNF alpha + IFN	21.0	8.4
gamma
HUVEC TNF alpha + IL4	12.1	11.0
HUVEC IL-11	13.6	4.4
Lung Microvascular EC none	25.2	18.4
Lung Microvascular EC	2.6	9.4
TNFalpha + IL-1beta
Microvascular Dermal EC	6.0	3.8
none
Microsvasular Dermal EC	0.0	3.7
TNFalpha + IL-1beta
Bronchial epithelium	9.3	10.2
TNFalpha + IL1beta
Small airway epithelium	0.0	10.0
none
Small airway epithelium	37.1	14.1
TNFalpha + IL-1beta
Coronery artery SMC rest	11.1	5.5
Coronery artery SMC	11.3	4.0
TNFalpha + IL-1beta
Astrocytes rest	0.0	1.1
Astrocytes TNFalpha + IL-	0.0	1.8
1beta
KU-812 (Basophil) rest	38.4	17.2
KU-812 (Basophil) PMA/	33.2	38.7
ionomycin
CCD1106 (Keratinocytes)	76.3	40.1
none
CCD1106 (Keratinocytes)	13.1	14.9
TNFalpha + IL-1beta
Liver cirrhosis	15.8	7.0
NCI-H292 none	35.1	20.2
NCI-H292 IL-4	45.4	25.5
NCI-H292 IL-9	60.7	31.2
NCI-H292 IL-13	45.4	38.4
NCI-H292 IFN gamma	26.2	16.7
HPAEC none	5.6	6.3
HPAEC TNFalpha + IL-1 beta	21.5	12.1
Lung fibroblast none	22.5	12.2
Lung fibroblast TNF	6.3	8.2
alpha + IL-1 beta
Lung fibroblast IL-4	16.0	13.5
Lung fibroblast IL-9	15.9	11.9
Lung fibroblast IL-13	0.0	5.8
Lung fibroblast IFN gamma	37.6	19.9
Dermal fibroblast CCD1070	32.3	17.2
rest
Dermal fibroblast CCD1070	100.0	54.7
TNF alpha
Dermal fibroblast CCD1070	34.6	18.7
IL-1 beta
Dermal fibroblast IFN	17.1	12.7
gamma
Dermal fibroblast IL-4	5.3	15.0
Dermal Fibroblasts rest	0.0	6.9
Neutrophils TNFa + LPS	0.0	2.7
Neutrophils rest	5.6	6.1
Colon	0.0	0.9
Lung	0.0	1.7
Thymus	15.2	18.2
Kidney	6.3	8.7

[0994] AI_comprehensive panel_v1.0 Summary: Ag5255 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[0995] CNS_neurodegeneration_v1.0 Summary: Ag5255 This panel confirms the expression of this gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.5 for a discussion of this gene in treatment of central nervous system disorders.

[0996] General_screen_panel_v1.5 Summary: Ag5255 Highest expression of this gene is detected in a colon cancer SW480 cell line (CT=31.6). Moderate to low 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.

[0997] In addition, this gene is expressed at moderate levels in cerebellum and fetal brain. Therefore, therapeutic modulation of this gene product may be useful in the treatment of central nervous system disorders such ataxia and autism.

[0998] Panel 4.1D Summary: Ag5255/Ag6844 Two experiments with different probe and primer sets are in good agreement. The highest expression of this gene is detected in TNF alpha activated dermal fibroblast and LPS activated monocytes (CTs=32.7-32.9). Moderate to low levels of expression of this gene is detected in activated polarized T cells, naive and memory T cells, PMA/ionomycin activated LAK cells, resting IL-2 treated NK cells, eosinophils, resting dendritic cells, activated basophils, resting keratinocyte, and activated mucoepidermoid NCI-H292 cells. Therefore, therapeutic modulation of this gene or its protein product may be useful in the treatment of autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.

[0999] AE. CG149964-01: Brain Mitochondrial Carrier Protein-1.

[1000] Expression of gene CG149964-01 was assessed using the primer-probe set Ag7056, described in Table AEA.

TABLE AEA
Probe Name Ag7056
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-tgtggttccaactgctcag-3′	19	617	360
Probe	TET-5′-ctggtagctctactcctacaacgatggcag-3′-TAMRA	30	640	361
Reverse	5′-agatccacatgtcccatcatt-3′	21	707	362

[1001] General_screen_panel_v1.6 Summary: Ag7056 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[1002] AF. CG150799-01, CG150799-02 and CG150799-03: MASS1.

[1003] Expression of gene CG150799-01, CG150799-02 and CG150799-03 was assessed using the primer-probe sets Ag5242, Ag5243, Ag5244, Ag5245, Ag5247 and Ag5248, described in Tables AFA, AFB and AFC. Results of the RTQ-PCR runs are shown in Tables AFD, AFE, AFF, AFG, AFH and AFI. Please note that probe-primer sets Ag5243 is specific for CG150799-02 and probe-primer sets Ag5244 and Ag5245 are specific for CG150799-03.

TABLE AFA
Probe Name Ag5242
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-acgaatcccatgtgacacttt-3′	21	3624	363
Probe	TET-5′-cccttcattataaaaccttgggttcca-3′-TAMRA	27	3645	364
Reverse	5′-tgactgttgtcttggcaatgt-3′	21	3681	365

[1004]

TABLE AFB
Probe Name Ag5243
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gactccttccaaaggctatattgt-3′	24	8809	366
Probe	TET-5′-cgattcaaggccctacaaatatctgcca-3′-TAMRA	28	8849	367
Reverse	5′-ccatttctggttccgtgtcta-3′	21	8880	368

[1005]

TABLE AFC
Probe Name g5244
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-actgataattctattcctgaactgga-3′	26	4927	369
Probe	TET-5′-agctctgctagatctatctacagatataacgctgtaaaatc-3′-TAMRA	41	4992	370
Reverse	5′-aactcattatagatcatccaaaagga-3′	26	5036	371

[1006]

TABLE AED
Probe Name g5245
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-accttgttgatgactttgctaatg-3′	24	4320	372
Probe	TET-5′-cagtggaactattacattccttccttggcaga-3′-TAMRA	32	4345	373
Reverse	5′-ggaagcgacacttcaatcaaa-3′	21	4387	374

[1007]

TABLE AFE
Probe Name Ag5247
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-acttacgttggacttaccatgg-3′	22	8183	375
Probe	TET-5′-caacttcatttcctcccagactaggtatgagg-3′-TAMRA	32	8211	376
Reverse	5′-tcatttcatttgaagtgagcaa-3′	22	8263	377

[1008]

TABLE AFF
Probe Name Ag5248
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-accttgttgatgactttgctaatg-3′	24	4320	378
Probe	TET-5′-cagtggaactattacattccttccttggcaga-3′-TAMRA	32	4345	379
Reverse	5′-caagaacatatatattcagagaacctctgatc-3′	30	4377	380

[1009]

TABLE AFG
AI_comprehensive_panel_v1.0
                                 Rel. Exp. (%)
                                 Ag5242, Run
Tissue Name                      305464510
110967 COPD-F                    0.1
110980 COPD-F                    1.1
110968 COPD-M                    0.1
110977 COPD-M                    4.4
110989 Emphysema-F               0.2
110992 Emphysema-F               2.7
110993 Emphysema-F               0.1
110994 Emphysema-F               0.1
110995 Emphysema-F               6.8
110996 Emphysema-F               2.0
110997 Asthma-M                  0.1
111001 Asthma-F                  0.5
111002 Asthma-F                  0.9
111003 Atopic Asthma-F           1.5
111004 Atopic Asthma-F           6.1
111005 Atopic Asthma-F           2.5
111006 Atopic Asthma-F           0.9
111417 Allergy-M                 0.8
112347 Allergy-M                 0.0
112349 Normal Lung-F             0.0
112357 Normal Lung-F             1.0
112354 Normal Lung-M             0.7
112374 Crohns-F                  0.5
112389 Match Control Crohns-F    0.2
112375 Crohns-F                  0.1
112732 Match Control Crohns-F    0.3
112725 Crohns-M                  0.1
112387 Match Control Crohns-M    0.1
112378 Crohns-M                  0.0
112390 Match Control Crohns-M    1.5
112726 Crohns-M                  1.2
112731 Match Control Crohns-M    0.9
112380 Ulcer Col-F               1.0
112734 Match Control Ulcer Col-F 0.8
112384 Ulcer Col-F               3.7
112737 Match Control Ulcer Col-F 0.8
112386 Ulcer Col-F               0.2
112738 Match Control Ulcer Col-F 0.5
112381 Ulcer Col-M               0.0
112735 Match Control Ulcer Col-M 0.0
112382 Ulcer Col-M               0.3
112394 Match Control Ulcer Col-M 0.1
112383 Ulcer Col-M               4.5
112736 Match Control Ulcer Col-M 0.3
112423 Psoriasis-F               0.2
112427 Match Control Psoriasis-F 2.3
112418 Psoriasis-M               0.1
112723 Match Control Psoriasis-M 0.5
112419 Psoriasis-M               0.0
112424 Match Control Psoriasis-M 0.2
112420 Psoriasis-M               1.8
112425 Match Control Psoriasis-M 3.7
104689 (MF) OA Bone-Backus       0.2
104690 (MF) Adj “Normal” Bone-Backus 0.6
104691 (MF) OA Synovium-Backus   0.1
104692 (BA) OA Cartilage-Backus  0.0
104694 (BA) OA Bone-Backus       0.2
104695 (BA) Adj “Normal” Bone-Backus 0.4
104696 (BA) OA Synovium-Backus   0.1
104700 (SS) OA Bone-Backus       0.9
104701 (SS) Adj “Normal” Bone-Backus 0.6
104702 (SS) OA Synovium-Backus   0.2
117093 OA Cartilage Rep7         0.9
112672 OA Bone5                  0.0
112673 OA Synovium5              0.1
112674 OA Synovial Fluid cells5  0.2
117100 OA Cartilage Rep14        0.0
112756 OA Bone9                  100.0
112757 OA Synovium9              6.4
112758 OA Synovial Fluid Cells9  0.1
117125 RA Cartilage Rep2         0.0
113492 Bone2 RA                  31.6
113493 Synovium2 RA              11.8
113494 Syn Fluid Cells RA        22.2
113499 Cartilage4 RA             22.7
113500 Bone4 RA                  28.1
113501 Synovium4 RA              20.2
113502 Syn Fluid Cells4 RA       16.4
113495 Cartilage3 RA             22.7
113496 Bone3 RA                  24.5
113497 Synovium3 RA              14.7
113498 Syn Fluid Cells3 RA       33.0
117106 Normal Cartilage Rep20    0.0
113663 Bone3 Normal              0.0
113664 Synovium3 Normal          0.0
113665 Syn Fluid Cells3 Normal   0.0
117107 Normal Cartilage Rep22    0.1
113667 Bone4 Normal              0.4
113668 Synovium4 Normal          0.1
113669 Syn Fluid Cells4 Normal   0.8

[1010]

TABLE AFH
CNS_neurodegeneration_v1.0
	Rel.	Rel.	Rel.	Rel.	Rel.	Rel.	Rel.	Rel.
	Exp.	Exp.	Exp.	Exp.	Exp.	Exp.	Exp.	Exp.
	(%)	(%)	(%)	(%)	(%)	(%)	(%)	(%)
	Ag5242,	Ag5242,	Ag5243,	Ag5243,	Ag5243,	Ag5244,	Ag5244,	Ag5244,
Tissue	Run	Run	Run	Run	Run	Run	Run	Run
Name	229661546	233609876	229661547	276863566	277731460	229661548	233610762	277731461
AD 1	22.4	21.6	29.3	31.6	27.5	9.1	0.0	3.1
Hippo
AD 2	47.3	42.0	54.7	53.2	44.8	0.0	2.9	4.0
Hippo
AD 3	12.2	13.5	17.8	13.6	10.9	0.0	0.0	0.0
Hippo
AD 4	14.8	14.4	16.6	17.7	20.6	0.0	0.0	0.0
Hippo
AD 5	65.5	84.1	61.6	63.7	57.4	6.7	0.0	4.3
Hippo
AD 6	56.3	59.5	82.4	84.7	90.1	74.2	57.8	51.8
Control 2	29.5	25.7	29.3	31.6	31.9	0.0	0.0	5.5
Hippo
Control 4	32.8	29.7	35.6	31.2	37.1	8.1	11.3	0.0
Hippo
Control	33.9	33.9	24.7	24.0	30.8	0.0	4.5	0.0
(Path) 3
Hippo
AD 1	32.3	33.9	32.3	34.6	35.4	2.0	5.4	2.9
Temporal
Ctx
AD 2	35.8	42.3	39.5	51.1	46.3	3.3	5.4	0.0
Temporal
Ctx
AD 3	28.3	21.2	20.4	23.5	20.7	0.0	0.0	0.0
Temporal
Ctx
AD 4	47.3	44.8	36.6	39.0	45.4	10.3	0.0	8.3
Temporal
Ctx
AD 5	73.7	100.0	100.0	100.0	100.0	0.0	11.4	17.6
Inf
Temporal
Ctx
AD 5	93.3	77.4	87.7	82.4	88.3	7.3	10.7	8.9
Sup
Temporal
Ctx
AD 6	59.0	58.2	62.0	0.0	58.2	55.9	94.0	49.0
Inf
Temporal
Ctx
AD 6	85.3	99.3	74.2	74.7	90.1	100.0	100.0	100.0
Sup
Temporal
Ctx
Control 1	47.6	46.3	27.4	28.5	29.1	1.7	0.0	0.0
Temporal
Ctx
Control 2	37.6	37.4	30.6	27.5	32.8	2.7	11.0	4.5
Temporal
Ctx
Control 3	27.5	24.1	27.4	32.8	37.6	7.1	5.4	2.6
Temporal
Ctx
Control 3	38.2	39.0	34.6	30.6	31.9	8.7	2.6	4.9
Temporal
Ctx
Control	66.0	81.2	54.0	58.6	52.5	2.5	0.0	3.2
(Path) 1
Temporal
Ctx
Control	43.5	50.0	40.1	41.8	41.5	2.0	10.9	0.0
(Path) 2
Temporal
Ctx
Control	23.3	24.5	19.9	21.5	22.4	2.9	2.3	7.7
(Path) 3
Temporal
Ctx
Control	52.5	48.0	33.7	39.8	39.0	0.0	4.7	4.3
(Path) 4
Temporal
Ctx
AD 1	18.0	18.8	22.8	25.7	24.3	0.0	3.0	0.0
Occipital
Ctx
AD 2	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Occipital
Ctx
(Missing)
AD 3	15.5	14.0	17.8	17.8	18.0	0.0	0.0	0.0
Occipital
Ctx
AD 4	17.3	23.7	25.3	27.5	24.3	3.3	3.1	3.3
Occipital
Ctx
AD 5	22.4	26.1	21.3	15.2	22.5	2.0	3.1	5.3
Occipital
Ctx
AD 6	28.9	21.6	19.1	20.4	18.9	11.7	15.6	2.8
Occipital
Ctx
Control 1	9.3	10.2	6.8	6.1	7.4	0.0	0.0	0.0
Occipital
Ctx
Control 2	34.9	33.0	24.7	28.7	31.6	0.0	5.1	7.4
Occipital
Ctx
Control 3	27.2	24.1	27.5	25.2	24.5	2.4	9.2	4.2
Occipital
Ctx
Control 4	19.6	20.3	18.0	26.8	21.2	0.0	1.6	0.0
Occipital
Ctx
Control	56.6	64.6	48.6	58.6	57.8	9.1	5.1	7.8
(Path) 1
Occipital
Ctx
Control	5.7	6.1	9.0	7.1	8.5	2.0	0.0	0.0
(Path) 2
Occipital
Ctx
Control	2.6	3.1	4.1	1.9	4.5	0.0	0.0	0.0
(Path) 3
Occipital
Ctx
Control	9.9	11.2	5.4	9.2	8.2	0.0	0.0	0.0
(Path) 4
Occipital
Ctx
Control 1	28.9	32.5	19.6	21.8	22.4	0.0	0.0	0.0
Parietal
Ctx
Control 2	100.0	90.8	79.0	83.5	76.3	7.9	23.8	9.7
Parietal
Ctx
Control 3	14.8	11.9	17.3	15.3	17.0	0.0	9.8	0.0
Parietal
Ctx
Control	62.4	68.3	57.8	70.2	63.7	4.2	3.8	0.0
(Path) 1
Parietal
Ctx
Control	17.1	19.8	22.1	21.0	25.9	1.9	10.4	0.0
(Path) 2
Parietal
Ctx
Control	12.0	10.2	11.7	8.4	13.9	2.8	5.3	0.0
(Path) 3
Parietal
Ctx
Control	30.1	25.5	26.1	25.7	29.1	1.5	0.0	0.0
(Path) 4
Parietal
Ctx
		Rel.	Rel.	Rel.	Rel.	Rel.	Rel.	Rel.
		Exp.	Exp.	Exp.	Exp.	Exp.	Exp.	Exp.
		(%)	(%)	(%)	(%)	(%)	(%)	(%)
		Ag5245,	Ag5245,	Ag5247,	Ag5247,	Ag5248,	Ag5248,	Ag5248,
	Tissue	Run	Run	Run	Run	Run	Run	Run
	Name	229661549	230510320	229661550	276863570	229661551	276863572	277731466
	AD 1	16.0	0.0	9.0	6.7	14.9	13.7	17.9
	Hippo
	AD 2	16.2	4.6	41.8	21.8	44.4	32.8	32.5
	Hippo
	AD 3	0.0	0.0	5.8	0.0	9.8	4.8	6.8
	Hippo
	AD 4	23.2	7.6	17.3	8.6	12.8	6.4	7.0
	Hippo
	AD 5	11.6	5.3	84.7	31.0	85.3	61.1	62.0
	Hippo
	AD 6	58.6	30.8	100.0	92.0	69.3	48.3	55.5
	Hippo
	Control 2	15.1	29.1	42.0	29.9	27.7	25.0	26.1
	Hippo
	Control 4	0.0	0.0	27.0	23.7	25.2	20.9	16.5
	Hippo
	Control	8.2	0.0	13.0	12.2	13.1	19.8	22.1
	(Path) 3
	Hippo
	AD 1	9.3	19.5	29.9	21.9	26.2	17.9	26.1
	Temporal
	Ctx
	AD 2	14.2	0.0	28.7	32.5	38.2	37.6	100.0
	Temporal
	Ctx
	AD 3	0.0	0.0	4.4	4.5	12.2	9.5	11.3
	Temporal
	Ctx
	AD 4	39.0	19.2	43.5	25.3	33.0	25.9	29.5
	Temporal
	Ctx
	AD 5	24.5	0.0	43.5	74.7	76.8	100.0	79.6
	Inf
	Temporal
	Ctx
	AD 5	29.1	3.3	45.7	59.0	82.4	70.7	64.2
	Sup
	Temporal
	Ctx
	AD 6	55.5	100.0	87.1	87.7	71.7	46.3	65.1
	Inf
	Temporal
	Ctx
	AD 6	99.3	73.7	95.9	97.3	97.3	60.3	94.0
	Sup
	Temporal
	Ctx
	Control 1	58.2	27.7	25.3	19.1	44.4	25.2	32.3
	Temporal
	Ctx
	Control 2	31.4	48.3	8.9	15.4	50.0	34.4	29.1
	Temporal
	Ctx
	Control 3	5.1	6.3	16.6	5.8	35.6	21.3	27.7
	Temporal
	Ctx
	Control 3	8.4	0.0	31.4	13.7	22.4	26.1	31.4
	Temporal
	Ctx
	Control	78.5	37.9	72.7	72.7	75.8	63.3	69.7
	(Path) 1
	Temporal
	Ctx
	Control	80.1	20.9	42.6	31.9	42.9	33.9	42.0
	(Path) 2
	Temporal
	Ctx
	Control	0.0	4.1	5.8	4.3	21.0	14.5	16.2
	(Path) 3
	Temporal
	Ctx
	Control	49.3	43.2	73.7	49.3	40.6	32.5	47.6
	(Path) 4
	Temporal
	Ctx
	AD 1	0.0	0.0	10.2	13.8	19.9	12.8	14.3
	Occipital
	Ctx
	AD 2	0.0	0.0	0.0	0.0	0.0	0.0	0.0
	Occipital
	Ctx
	(Missing)
	AD 3	3.2	0.0	10.2	0.0	10.3	5.2	5.5
	Occipital
	Ctx
	AD 4	28.7	6.7	22.2	23.0	8.6	17.0	21.5
	Occipital
	Ctx
	AD 5	25.7	5.1	16.7	8.7	3.3	20.9	18.4
	Occipital
	Ctx
	AD 6	0.0	18.2	12.1	0.0	29.9	18.0	24.7
	Occipital
	Ctx
	Control 1	4.3	7.8	5.6	0.0	4.8	3.7	3.3
	Occipital
	Ctx
	Control 2	31.2	17.9	7.9	4.6	39.5	20.2	28.3
	Occipital
	Ctx
	Control 3	7.0	0.0	13.8	0.0	14.5	17.6	16.8
	Occipital
	Ctx
	Control 4	0.0	0.0	12.5	5.6	15.4	8.8	12.9
	Occipital
	Ctx
	Control	66.4	30.6	69.7	57.0	76.3	42.6	55.5
	(Path) 1
	Occipital
	Ctx
	Control	5.6	0.0	1.6	0.0	16.3	3.8	4.1
	(Path) 2
	Occipital
	Ctx
	Control	0.0	0.0	0.0	0.0	1.5	1.8	1.7
	(Path) 3
	Occipital
	Ctx
	Control	11.7	15.7	5.1	7.2	2.1	0.3	5.0
	(Path) 4
	Occipital
	Ctx
	Control 1	0.0	3.6	9.8	16.4	23.8	16.3	17.1
	Parietal
	Ctx
	Control 2	26.8	12.2	39.0	37.9	100.0	44.1	63.3
	Parietal
	Ctx
	Control 3	0.0	0.0	1.7	7.2	12.9	8.5	11.3
	Parietal
	Ctx
	Control	100.0	55.9	41.5	100.0	99.3	53.2	71.2
	(Path) 1
	Parietal
	Ctx
	Control	30.8	0.0	17.9	18.0	6.3	10.2	15.8
	(Path) 2
	Parietal
	Ctx
	Control	6.3	0.0	3.9	0.0	3.2	4.9	4.2
	(Path) 3
	Parietal
	Ctx
	Control	59.0	40.9	23.7	30.1	25.9	26.4	17.8
	(Path) 4
	Parietal
	Ctx

[1011]

TABLE AFI
General_screening_panel_v1.5
	Rel.	Rel.	Rel.	Rel.	Rel.
	Exp.	Exp.	Exp.	Exp.	Exp.
	(%)	(%)	(%)	(%)	(%)
	Ag5242,	Ag5243,	Ag5245,	Ag5247,	Ag5248,
Tissue	Run	Run	Run	Run	Run
Name	229665046	229665047	229665049	229665052	229665053
Adipose	0.1	0.0	0.0	0.0	0.0
Melanoma*	0.8	0.5	0.0	0.0	1.2
Hs688(A).T
Melanoma*	0.1	0.0	0.0	0.0	0.0
Hs688(B).T
Melanoma* M14	0.2	0.3	0.0	0.0	0.1
Melanoma*	0.9	0.2	0.0	0.0	0.1
LOXIMVI
Melanoma*	0.6	1.6	0.0	1.2	0.0
SK-MEL-5
Squamous cell	0.0	0.0	0.0	0.0	0.0
carcinoma SCC-4
Testis	2.9	3.4	0.0	3.3	3.8
Pool
Prostate ca.*	89.5	86.5	5.8	18.2
(bone met) PC-3
Prostate	10.7	8.5	0.7	2.4	7.0
Pool
Placenta	0.0	0.1	0.0	1.0	0.1
Uterus	0.0	0.1	0.0	0.0	0.1
Pool
Ovarian ca.	10.5	18.7	12.1	1.7
OVCAR-3
Ovarian ca.	0.2	0.1	0.0	0.2	0.0
SK-OV-3
Ovarian ca.	0.1	0.0	0.0	0.0	0.1
OVCAR-4
Ovarian ca.	7.3	7.1	0.0	3.7	12.1
OVCAR-5
Ovarian ca.	1.4	3.5	0.0	0.0	0.5
IGROV-1
Ovarian ca.	8.5	13.0	0.9	0.5	10.7
OVCAR-8
Ovary	0.1	0.4	0.0	0.0	1.0
Breast ca.	11.1	10.2	0.0	3.6	16.4
MCF-7
Breast ca.	3.7	4.8	3.2	0.6	5.9
MDA-MB-231
Breast ca.	0.0	0.0	0.0	0.0	0.0
BT 549
Breast ca.	10.2	4.4	0.0	3.1	9.9
T47D
Breast ca.	0.1	0.2	0.0	0.0	0.5
MDA-N
Breast	0.8	1.9	0.0	0.9	1.5
Pool
Trachea	7.4	6.4	0.9	20.3	9.5
Lung	0.3	0.0	0.0	0.0	0.1
Fetal	25.7	20.9	1.7	6.7	22.2
Lung
Lung ca.	3.4	3.6	0.0	0.7	11.6
NCI-N417
Lung ca.	0.1	0.0	0.0	0.0	0.0
LX-1
Lung ca.	26.1	28.9	27.9	7.7	24.7
NCI-H146
Lung ca.	100.0	100.0	100.0	42.9	98.6
SHP-77
Lung ca.	0.9	1.3	0.0	0.0	1.1
A549
Lung ca.	1.8	1.1	0.0	0.0	1.9
NCI-H526
Lung ca.	0.0	0.0	0.0	0.0	0.2
NCI-H23
Lung ca.	5.4	3.3	9.3	48.3	23.5
NCI-H460
Lung ca.	7.0	8.8	0.0	0.0	8.4
HOP-62
Lung ca.	0.0	0.0	0.0	0.0	0.0
NCI-H522
Liver	0.0	0.0	0.0	0.0	0.0
Fetal	0.0	0.0	0.0	0.6	0.2
Liver
Liver ca.	0.0	0.1	0.0	0.0	0.0
HepG2
Kidney	1.0	1.0	0.0	0.4	1.6
Pool
Fetal	8.5	6.9	1.0	6.5	9.2
Kidney
Renal ca.	0.0	0.0	0.0	0.0	0.0
786-0
Renal ca.	0.1	0.0	0.0	0.0	0.0
A498
Renal ca.	0.4	0.1	0.0	0.0	0.5
ACHN
Renal ca.	0.0	0.1	0.0	0.0	0.0
UO-31
Renal ca.	0.0	0.1	0.0	0.0	0.0
TK-10
Bladder	2.6	1.8	0.0	2.5	3.7
Gastric ca.	0.0	0.0	0.0	0.0	0.0
(liver met.)
NCI-N87
Gastric ca.	0.0	0.0	0.0	0.0	0.1
KATO III
Colon ca.	5.2	4.6	0.4	0.6	3.7
SW-948
Colon ca.	4.6	3.7	0.0	1.1	5.9
SW480
Colon ca.*	0.1	0.0	0.0	0.0	0.0
(SW480 met)
SW620
Colon ca.	0.0	0.0	0.0	0.0	0.0
HT29
Colon ca.	12.2	11.9	0.4	4.4	14.2
HTC-116
Colon ca.	13.8	14.0	8.9	6.6	16.4
CaCo-2
Colon	0.0	0.0	0.0	0.0	0.0
cancer
tissue
Colon ca.	0.1	0.0	0.0	0.0	0.0
SW1116
Colon ca.	0.0	0.0	0.0	0.0	1.2
Colo-205
Colon ca.	0.0	0.0	0.0	0.0	0.0
SW-48
Colon	0.1	0.0	0.0	0.6	0.1
Pool
Small	3.7	1.6	1.6	1.0	4.1
Intestine
Pool
Stomach	1.6	0.7	0.0	0.4	0.9
Pool
Bone	0.1	0.0	0.0	0.0	0.1
Marrow
Pool
Fetal	0.0	0.0	0.0	0.3	0.0
Heart
Heart Pool	0.1	0.0	0.0	0.7	0.1
Lymph	0.5	0.0	0.0	0.6	0.1
Node Pool
Fetal	0.2	0.0	0.0	1.1	0.0
Skeletal
Muscle
Skeletal	0.0	0.1	0.0	0.8	0.1
Muscle
Pool
Spleen	1.5	0.1	0.5	2.3	0.6
Pool
Thymus	3.2	1.7	1.9	0.7	2.9
Pool
CNS cancer	4.4	2.6	0.3	1.2	3.2
(glio/astro)
U87-MG
CNS cancer	0.1	0.0	0.0	0.0	0.0
(glio/astro)
U-118-MG
CNS cancer	0.0	0.0	0.0	0.0	0.0
(neuro; met)
SK-N-AS
CNS cancer	0.2	0.0	0.0	0.0	0.1
(astro)
SF-539
CNS cancer	0.1	0.1	0.0	0.0	0.2
(astro)
SNB-75
CNS cancer (glio)	2.0	4.1	0.0	0.6	3.4
SNB-19
CNS cancer (glio)	2.4	3.3	0.4	0.3	4.1
SF-295
Brain	13.4	29.1	1.8	4.2	14.6
(Amygdala)
Pool
Brain	14.2	13.4	0.8	6.1	15.6
(cerebellum)
Brain	89.5	100.0	15.1	100.0	93.3
(fetal)
Brain	35.4	47.3	6.6	13.7	31.9
(Hippocampus)
Pool
Cerebral	40.1	53.2	8.9	35.1	39.0
Cortex
Pool
Brain	14.2	33.7	4.7	2.2	16.7
(Substantia
nigra)
Pool
Brain	37.9	43.2	0.8	25.5	45.1
(Thalamus)
Pool
Brain	13.9	25.7	2.1	13.4	18.6
(whole)
Spinal	2.2	2.6	1.7	1.4	2.4
Cord Pool
Adrenal	0.7	0.7	0.8	1.9	0.3
Gland
Pituitary	18.6	16.3	5.0	3.2	36.6
gland Pool
Salivary	0.1	0.5	0.0	0.0	0.1
Gland
Thyroid	11.6	12.2	0.2	0.7	9.4
(female)
Pancreatic ca.	0.1	0.0	0.0	0.0	0.1
CAPAN2
Pancreas	3.6	2.3	0.0	1.7	2.0
Pool

[1012]

TABLE AFJ
General_screening_panel_v1.6
	Rel.	Rel.	Rel.	Rel.	Rel.	Rel.	Rel.	Rel.
	Exp. (%)	Exp. (%)	Exp. (%)	Exp. (%)	Exp. (%)	Exp. (%)	Exp. (%)	Exp. (%)
	Ag5243,	Ag5243,	Ag5245,	Ag5245,	Ag5247,	Ag5247,	Ag5248,	Ag5248,
	Run	Run	Run	Run	Run	Run	Run	Run
Tissue Name	277218719	277729929	277219697	277730879	277219699	277729933	277219701	277730881
Adipose	0.1	0.2	0.0	0.0	0.0	0.0	0.1	0.1
Melanoma*	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Hs688(A).T
Melanoma*	0.0	0.0	0.0	0.0	0.0	0.0	0.2	0.0
Hs688(B).T
Melanoma*	0.2	0.0	0.7	0.0	0.0	0.0	0.0	0.3
M14
Melanoma*	0.2	0.1	0.0	0.0	0.0	0.0	0.1	0.2
LOXIMVI
Melanoma*	2.5	1.3	0.0	0.0	0.0	0.9	0.1	0.4
SK-MEL-5
Squamous cell	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.1
carcinoma
SCC-4
Testis Pool	2.2	3.4	3.1	2.3	7.1	3.5	2.7	2.8
Prostate ca.*	95.3	76.8	11.5	1.3	23.7	20.3	76.8	63.3
(bone met)
PC-3
Prostate Pool	6.8	7.5	0.0	0.0	6.3	8.7	6.1	7.0
Placenta	0.0	0.0	0.0	0.0	0.0	0.0	0.1	0.1
Uterus Pool	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.1
Ovarian ca.	13.2	11.7	9.5	4.0	3.3	5.2	11.6	14.5
OVCAR-3
Ovarian ca.	0.2	0.3	0.0	0.0	0.0	0.0	0.1	0.3
SK-OV-3
Ovarian ca.	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
OVCAR-4
Ovarian ca.	6.6	7.4	2.3	0.0	4.7	0.8	4.7	5.1
OVCAR-5
Ovarian ca.	2.0	2.8	0.7	0.0	0.0	0.0	1.1	3.3
IGROV-1
Ovarian ca.	14.2	8.1	3.6	0.0	7.5	8.1	8.2	13.4
OVCAR-8
Ovary	0.1	0.6	0.0	0.0	0.0	0.0	0.7	0.2
Breast ca.	7.4	8.0	0.0	0.0	3.5	9.4	8.0	9.2
MCF-7
Breast ca.	6.5	3.0	2.4	2.5	0.4	0.7	4.1	6.4
MDA-MB-231
Breast ca. BT 549	0.0	0.0	0.0	0.0	0.0	1.0	0.0	0.0
Breast ca.	6.7	3.8	0.8	0.0	5.5	1.5	4.7	8.0
T47D
Breast ca.	0.0	0.2	0.5	0.0	0.0	0.5	0.1	0.3
MDA-N
Breast Pool	0.2	0.1	0.9	0.0	0.0	0.0	0.5	0.3
Trachea	18.6	15.6	3.9	0.0	14.6	18.0	5.5	7.6
Lung	0.2	0.0	0.0	0.0	0.0	1.2	0.0	0.1
Fetal Lung	21.3	21.0	0.0	0.7	10.3	5.1	19.3	23.7
Lung ca.	6.3	3.2	0.0	0.0	1.7	4.2	2.4	2.0
NCI-N417
Lung ca. LX-1	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Lung ca.	23.3	20.4	17.0	100.0	7.1	9.8	16.8	16.4
NCI-H146
Lung ca.	95.9	77.9	100.0	35.6	24.7	31.9	100.0	76.3
SHP-77
Lung ca. A549	1.0	0.4	0.0	0.0	0.0	0.0	0.3	1.1
Lung ca.	1.4	1.9	0.0	0.0	0.0	0.0	0.7	0.5
NCI-H526
Lung ca.	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.1
NCI-H23
Lung ca.	2.8	2.1	0.0	0.0	0.9	0.9	3.1	3.4
NCI-H460
Lung ca.	12.4	6.5	0.0	0.0	0.6	0.0	9.4	11.6
HOP-62
Lung ca.	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
NCI-H522
Liver	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Fetal	0.0	0.0	0.0	0.0	0.0	0.9	0.2	0.0
Liver
Liver ca.	0.2	0.0	0.0	0.0	0.0	0.0	0.0	0.1
HepG2
Kidney	0.5	0.9	0.0	0.0	1.0	0 0	0.6	1.8
Pool
Fetal	5.8	6.8	0.0	0.0	11.4	6.6	4.3	7.9
Kidney
Renal ca.	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
786-0
Renal ca.	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
A498
Renal ca.	0.0	0.2	0.0	0.0	0.0	0.0	0.2	0.1
ACHN
Renal ca.	0.2	0.2	0.0	0.0	0.0	0.0	0.0	0.1
UO-31
Renal ca.	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
TK-10
Bladder	1.2	1.5	0.0	0.0	3.8	1.4	3.3	3.2
Gastric ca.	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
(liver met.)
NCI-N87
Gastric ca.	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
KATO III
Colon ca.	4.0	4.4	0.7	0.0	2.8	0.6	3.6	3.8
SW-948
Colon ca.	3.6	4.0	0.5	0.0	0.0	2.3	2.7	4.2
SW480
Colon ca.*	0.2	0.0	0.0	0.0	0.0	0.0	0.0	0.0
(SW480 met)
SW620
Colon ca.	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
HT29
Colon ca.	13.8	12.7	1.0	0.0	6.8	3.1	5.6	14.7
HCT-116
Colon ca.	18.8	14.9	10.8	4.7	10.2	10.1	2.4	11.6
CaCo-2
Colon cancer	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.1
tissue
Colon ca.	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
SW1116
Colon ca.	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Colo-205
Colon ca.	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
SW-48
Colon Pool	0.1	0.0	0.0	0.0	0.9	0.0	0.4	0.1
Small	0.7	1.4	1.6	1.6	0.7	3.0	8.9	1.7
Intestine
Pool
Stomach	0.6	1.0	0.0	0.0	0.0	0.0	0.7	0.6
Pool
Bone	0.0	0.1	0.0	0.0	0.0	0.6	0.0	0.1
Marrow
Pool
Fetal	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.1
Heart
Heart Pool	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Lymph	0.0	0.7	0.0	0.0	0.8	0.0	0.5	0.4
Node Pool
Fetal	0.4	0.1	0.0	0.0	0.0	0.0	0.1	0.2
Skeletal
Muscle
Skeletal	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
Muscle
Pool
Spleen	0.0	0.1	0.6	0.0	1.4	0.0	0.6	0.5
Pool
Thymus	2.0	2.1	1.0	0.7	1.4	2.6	1.9	3.2
Pool
CNS cancer	2.6	2.5	0.8	0.0	0.7	0.6	3.7	4.3
(glio/astro)
U87-MG
CNS cancer	0.3	0.1	0.0	0.0	0.0	0.0	0.0	0.0
(glio/astro)
U-118-MG
CNS cancer	0.0	0.0	0.0	0.0	0.0	0.0	0.0	0.0
(neuro; met)
SK-N-AS
CNS cancer	0.0	0.0	0.0	0.0	0.0	0.0	0.1	0.1
(astro) SF-539
CNS cancer	0.2	0.3	0.0	0.0	0.0	0.0	0.5	0.3
(astro)
SNB-75
CNS cancer	3.1	2.4	0.0	0.0	0.0	1.1	1.9	3.4
(glio) SNB-19
CNS cancer	2.8	2.2	0.5	0.6	0.9	2.6	3.1	2.8
(glio) SF-295
Brain	23.2	18.7	1.0	2.6	7.1	2.2	12.2	14.0
(Amygdala)
Pool
Brain	13.8	11.7	3.1	1.0	10.2	11.3	13.3	14.1
(cerebellum)
Brain (fetal)	100.0	100.0	20.6	14.8	100.0	100.0	73.2	100.0
Brain	51.1	40.3	6.9	5.3	25.9	14.3	26.8	35.8
(Hippocampus)
Pool
Cerebral	52.5	52.5	8.2	0.0	27.0	20.9	31.9	31.0
Cortex
Pool
Brain	29.5	29.1	1.1	1.7	5.5	2.9	9.7	12.2
(Substantia
nigra) Pool
Brain	48.3	51.1	2.2	2.5	21.9	25.2	17.4	31.0
(Thalamus)
Pool
Brain (whole)	28.7	30.6	6.0	4.2	15.2	13.3	9.2	14.7
Spinal	1.9	1.3	1.3	0.0	1.0	0.0	1.6	2.2
Cord Pool
Adrenal	0.4	0.8	1.5	0.0	0.0	0.8	0.3	0.4
Gland
Pituitary	17.9	13.7	2.6	7.4	0.0	11.1	13.4	15.8
gland Pool
Salivary	0.2	0.3	0.0	0.0	0.0	0.0	0.3	0.6
Gland
Thyroid	12.9	10.0	1.4	0.0	1.5	0.8	8.5	13.9
(female)
Pancreatic ca.	0.0	0.0	0.0	0.0	0.0	0.0	0.1	0.0
CAPAN2
Pancreas	2.6	3.2	0.0	0.0	0.6	3.6	4.5	3.7
Pool

[1013]

TABLE AFK
Panel 4.1D
	Rel.	Rel.	Rel.	Rel.
	Exp. (%)	Exp. (%)	Exp. (%)	Exp. (%)
	Ag5242,	Ag5245,	Ag5247,	Ag5248,
	Run	Run	Run	Run
Tissue Name	229819771	229819577	229819792	229819793
Secondary Th1 act	0.0	0.0	0.0	0.0
Secondary Th2 act	0.6	4.1	0.7	0.5
Secondary Tr1 act	2.3	1.2	0.6	2.3
Secondary Th1 rest	0.0	0.0	0.0	0.1
Secondary Th2 rest	13.7	0.6	5.1	12.2
Secondary Tr1 rest	15.5	1.9	8.7	14.0
Primary Th1 act	100.0	71.7	100.0	85.3
Primary Th2 act	27.9	12.6	20.4	28.3
Primary Tr1 act	36.6	9.4	24.3	28.9
Primary Th1 rest	15.9	2.9	5.1	14.6
Primary Th2 rest	34.2	3.4	23.3	29.1
Primary Tr1 rest	12.0	5.0	12.7	12.9
CD45RA CD4	0.6	0.0	0.0	0.0
lymphocyte act
CD45RO CD4	0.0	0.0	0.0	0.2
lymphocyte act
CD8 lymphocyte act	5.6	2.9	0.7	7.3
Secondary CD8	0.0	0.0	0.0	0.0
lymphocyte rest
Secondary CD8	2.1	0.0	0.0	1.9
lymphocyte act
CD4 lymphocyte none	8.1	1.2	5.8	7.4
2ry	0.0	0.0	0.0	0.0
Th1/Th2/Tr1_anti-
CD95 CH11
LAK cells rest	0.1	0.0	0.6	0.1
LAK cells IL-2	0.3	0.0	0.0	0.3
LAK cells	25.2	3.1	4.8	24.0
IL-2 + IL-12
LAK cells	0.2	0.0	0.0	1.1
IL-2 + IFN gamma
LAK cells IL-2 + IL-18	0.5	0.0	0.7	0.7
LAK cells	0.2	0.0	0.6	0.0
PMA/ionomycin
NK Cells IL-2 rest	0.5	1.9	0.0	0.5
Two Way MLR 3 day	4.5	5.1	0.7	2.3
Two Way MLR 5 day	6.7	14.9	9.5	15.0
Two Way MLR 7 day	0.2	0.0	0.0	0.1
PBMC rest	8.7	0.0	2.3	6.0
PBMC PWM	0.2	0.0	0.0	0.4
PBMC PHA-L	0.2	0.0	0.0	0.1
Ramos (B cell) none	3.6	2.2	1.1	1.9
Ramos (B cell) ionomycin	1.8	3.6	1.5	2.2
B lymphocytes PWM	1.3	0.0	2.0	1.1
B lymphocytes	0.8	0.7	1.2	1.5
CD40L and IL-4
EOL-1 dbcAMP	3.7	6.7	3.3	2.0
EOL-1 dbcAMP	3.0	0.0	2.3	2.0
PMA/ionomycin
Dendritic cells none	10.7	1.9	3.8	13.6
Dendritic cells LPS	4.7	6.2	11.7	8.2
Dendritic cells anti-CD40	0.1	0.0	0.0	0.0
Monocytes rest	11.6	0.6	2.8	16.4
Monocytes LPS	4.6	5.6	1.4	5.4
Macrophages rest	0.2	0.0	0.0	0.1
Macrophages LPS	11.5	0.0	0.9	9.2
HUVEC none	0.3	0.0	0.0	0.5
HUVEC starved	15.9	8.4	2.4	15.5
HUVEC IL-1beta	0.2	0.0	0.0	0.1
HUVEC IFN gamma	0.0	0.0	0.0	0.0
HUVEC TNF alpha +IFN gamma	6.0	0.0	2.4	7.7
HUVEC TNF alpha + IL4	1.0	0.0	0.6	4.2
HUVEC IL-11	9.6	1.6	6.4	9.2
Lung Microvascular EC none	3.6	0.9	1.0	2.4
Lung Microvascular	0.0	0.0	0.0	0.0
EC TNF alpha + IL-1beta
Microvascular	0.1	0.0	0.0	0.3
Dermal EC none
Microvascular	0.0	0.0	0.0	0.0
Dermal EC
TNF alpha + IL-1beta
Bronchial epithelium	0.1	0.0	0.0	0.0
TNF alpha + IL1beta
Small airway	0.2	0.0	0.0	0.2
epithelium none
Small airway	3.1	0.0	0.7	3.7
epithelium TNF alpha + IL-1beta
Coronery artery	4.1	0.0	0.6	3.6
SMC rest
Coronery artery	3.1	0.0	0.0	2.6
SMC TNF alpha + IL-1beta
Astrocytes rest	3.8	0.9	0.6	4.0
Astrocytes TNF alpha + IL-1beta	0.0	0.0	0.0	0.0
KU-812 (Basophil) rest	0.0	0.0	0.0	0.0
KU-812 (Basophil)	12.6	1.0	4.5	15.4
PMA/ionomycin
CCD1106	15.7	15.5	4.3	15.8
(Keratinocytes) none
CCD1106	0.0	0.0	0.0	0.0
(Keratinocytes)
TNF alpha + IL-1beta
Liver cirrhosis	0.1	0.0	0.0	0.0
NCI-H292 none	0.0	0.0	0.0	0.0
NCI-H292 IL-4	0.0	0.0	0.0	0.0
NCI-H292 IL-9	0.0	0.0	0.0	0.0
NCI-H292 IL-13	0.2	0.0	0.0	0.0
NCI-H292 IFN gamma	0.0	0.0	0.0	0.0
HPAEC none	0.0	0.0	0.0	0.0
HPAEC TNF alpha + IL-1beta	0.1	0.0	0.0	0.0
Lung fibroblast none	0.0	0.0	0.0	0.0
Lung fibroblast TNF	19.9	25.7	4.4	22.8
alpha + IL-1beta
Lung fibroblast IL-4	72.2	100.0	32.8	49.7
Lung fibroblast IL-9	1.2	0.0	0.4	0.6
Lung fibroblast IL-13	1.8	0.0	1.5	1.2
Lung fibroblast IFN gamma	0.0	0.0	0.0	0.0
Dermal fibroblast	0.1	0.0	0.0	0.0
CCD1070 rest
Dermal fibroblast	2.9	0.0	1.3	5.3
CCD1070 TNF alpha
Dermal fibroblast	6.3	0.0	1.7	7.7
CCD1070 IL-1beta
Dermal fibroblast	0.0	0.0	0.0	0.0
IFN gamma
Dermal fibroblast IL4	0.0	0.0	0.0	0.0
Dermal Fibroblasts rest	0.0	0.0	0.0	0.0
Neutrophils	0.1	0.0	0.0	0.0
TNFa + LPS
Neutrophils rest	87.7	11.7	28.3	100.0
Colon	0.0	0.0	0.0	0.0
Lung	0.2	0.0	0.0	0.3
Thymus	0.1	0.0	0.0	0.6
Kidney	0.1	0.0	1.4	0.6

[1014]

TABLE AFL
general oncology screening panel_v_2.4
	Rel.	Rel.	Rel.		Rel.	Rel.	Rel.
	Exp. (%)	Exp. (%)	Exp. (%)		Exp. (%)	Exp. (%)	Exp. (%)
	Ag5242,	Ag5247,	Ag5248,		Ag5242,	Ag5247,	Ag5248,
	Run	Run	Run		Run	Run	Run
Tissue Name	260269083	260269132	260269133	Tissue Name	260269083	260269132	260269133
Colon cancer 1	0.0	0.0	3.5	Bladder cancer	0.0	0.0	0.0
				NAT 2
Colon cancer	7.2	0.0	11.0	Bladder cancer	0.0	0.0	0.0
NAT 1				NAT 3
Colon cancer 2	0.0	0.0	0.0	Bladder cancer	0.0	0.0	0.0
				NAT 4
Colon cancer	17.6	16.6	15.7	Prostate	2.4	20.9	5.8
NAT 2				adenocarcinoma 1
Colon cancer 3	4.5	0.0	3.8	Prostate	0.0	0.0	2.0
				adenocarcinoma 2
Colon cancer	37.1	0.0	27.0	Prostate	71.7	55.9	54.3
NAT3				adenocarcinoma 3
Colon	6.1	0.0	1.0	Prostate	1.0	0.0	7.2
malignant				adenocarcinoma 4
cancer 4
Colon normal	0.0	0.0	2.4	Prostate cancer	4.5	0.0	0.0
adjacent tissue 4				NAT 5
Lung cancer 1	25.0	17.9	4.2	Prostate	30.6	4.5	11.1
				adenocarcinoma 6
Lung NAT 1	2.3	3.9	12.9	Prostate	14.4	6.3	23.0
				adenocarcinoma 7
Lung cancer 2	40.1	100.0	100.0	Prostate	9.1	5.0	6.8
				adenocarcinoma 8
Lung NAT 2	32.3	18.2	48.6	Prostate	75.3	10.7	31.0
				adenocarcinoma 9
Squamous cell	73.2	47.0	82.4	Prostate cancer	0.0	0.0	7.1
carcinoma 3				NAT 10
Lung NAT 3	13.3	3.5	5.8	Kidney cancer 1	0.0	0.0	0.0
metastatic	4.4	0.0	1.5	KidneyNAT 1	33.7	11.7	10.7
melanoma 1
Melanoma 2	0.0	0.0	1.4	Kidney cancer 2	10.7	7.4	2.8
Melanoma 3	9.8	0.0	4.2	Kidney NAT 2	100.0	42.9	51.4
metastatic	2.1	0.0	1.0	Kidney cancer 3	61.1	8.6	24.8
melanoma 4
metastatic	6.4	9.3	2.2	Kidney NAT 3	63.3	16.0	29.9
melanoma 5
Bladder cancer 1	0.0	0.0	0.0	Kidney cancer 4	8.8	0.0	1.9
Bladder cancer	0.0	0.0	0.0	Kidney NAT 4	5.3	0.0	9.2
NAT 1
Bladder cancer 2	2.1	0.0	0.0

[1015] AI_comprehensive panel_v1.0 Summary: Ag5242 Highest expression is seen in osteoarthritic bone sample (CT=27.5). Prominenet levels of expression are seen in a cluster of samples derived from RA. Thus, expression of this gene could be used to differentiate between these samples and other samples on this panel and as a marker of rheumatoid arthritis. In addition, modulation of the expression or function of this gene may be useful in the treatment of RA.

[1016] CNS_neurodegeneration_v1.0 Summary: Ag5242/Ag5243/Ag5247/Ag5248 Multiple experiments with four different probe and primer sets produce results that are in reasonable agreement. These panels do not show differential expression of this gene in Alzheimer's disease. However, these profiles confirm the expression of this gene at moderate levels in the brain. Please see Panel 1.5 for discussion of this gene in the central nervous system.

[1017] Ag5244 Three experiments with Ag5244, which is specific for CG150799-03, detect expression of this gene at low but significant levels in the hippocampus and temporal cortex of Alzheimer's patients. This expression may suggest an involvement of this gene product in the etiology of this disease.

[1018] One experiment with Ag5244 (Run 276863567) and two experiments with Ag5245 (Run 276863569 and Run 277731463), also specific for CG150799-03, show low/undetectable levels of expression (CTs>35). (Data not shown). Two additional experiments with Ag5245 show low expression in samples from the parietal cortex of a normal patient and the inferior temporal cortex of an Alzheimer's patient.

[1019] General_screen_panel_v1.5

[1020] Summary: Ag5242/Ag5243/Ag5245/Ag5247/Ag5248 Multiple experiments with five different probe and primer sets produce results that are in reasonable agreement. Highest expression is seen in cell lines from lung and prostate cancers and the fetal brain (CTs=28-30). This gene, which encodes a MASS 1 homolog, appears be preferentially expressed in the brain, with prominent levels of expression in all regions of the CNS examined. MASS 1 is a large, calcium-binding GPCR expressed in the central nervous system that may play a fundamental role in its development (MacMillan, J Biol Chem 2002 Jan 4;277(1):785-92). In addition, this gene has been associated with some nonsymptomatic epilepsies (Skardski, Neuron, Vol 31, 537-544, August 2001). Thus, based on the homology of this protein to MASSI and the preferential expression in the brain, expression of this gene could be used to differentiate between brain and non-neural tissue. In addition, 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.

[1021] Moderate levels of expression are also seen in samples from lung, colon, ovarian and prostate cancer cell lines. This suggests that expression of this gene could be used as a marker of these cancers. Futhermore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of these cancers.

[1022] Ag5244 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[1023] General_screen_panel_v1.6 Summary: Ag5243/Ag5247/Ag5248/Ag5245 Multiple experiments with three different probe and primer sets produce results that are in very good agreement. Highest expression is seen in a lung cancer cell line and the fetal brain (CTs=27-32). Overall, expression is in excellent agreement with Panel 1.5, with prominent expression seen in all regions of the CNS, and lung and prostate cancer cell lines. Please see Panel 1.5 for further discussion of this gene.

[1024] Ag5244 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[1025] Panel 4.1D Summary: Ag5242/Ag5243/Ag5247/Ag5248 Multiple experiments with four different probe and primers sets show highest expression of this gene in primary activated Th1 cells and resting neutrophils (CTs=27-31). Since this gene is expressed predominantly in activated Th-1 vs Th-2 cells, regulation of the expression of this gene might also be important for autoimmune disease such as rheumatoid arthritis (please see also AI panel). Moderate levels of expression are also seen in IL-4 treated lung fibroblasts and resting neutrophils. Thus, therapeutic regulation of the transcript or the protein encoded by the transcript could be important in immune modulation and in the treatment of T cell-mediated diseases such as asthma, arthritis, psoriasis, IBD, and lupus.

[1026] Ag5245 Highest expression of this gene is seen in IL-4 treated lung fibroblasts (CT=32). Low but significant expression is also seen in TNF-a/IL1-b treated lung fibroblasts and primary activated Th1 cells. Three experiments with the probe and primer set Ag5244 show low/undetectable levels of results (CTs>35).

[1027] General oncology screening panel_v—2.4

[1028] Summary: Ag5242/Ag5243/Ag5247/Ag5248 Four experiments with the different probe and primer sets show highest expression in a lung cancers and normal kidney tissue adjacent to a tumor (CTs=31-34). Overall, this gene is expressed at low but significant levels in prostate cancer, normal kidney and kidney cancer, squamous cell carcinoma and normal colon. Therefore, therapeutic modulation of this gene or its protein product may be useful in the treatment of lung, prostate and kidney cancers.

[1029] Ag5244/Ag5245 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[1030] AG. CG151014-01: Metabotropic Glutamate Receptor 3-Variant

[1031] Expression of gene CG151014-01 was assessed using the primer-probe set Ag5219, described in Table AGA. Results of the RTQ-PCR runs are shown in Tables AGB, AGC and AGD.

TABLE AGA
Probe Name Ag5219
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-tgattgtgaattgcagttcagt-3′	22	2550	381
Probe	TET-5′-aagtgctcacgtgcagctccagaata-3′-TAMRA	26	2598	382
Reverse	5′-gtactagggttgttcttttgctct-3′	24	2631	383

[1032]

TABLE AGB
CNS_neurodegeneration_v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag5219,		Ag5219,
	Run		Run
Tissue Name	228020421	issue Name	228020421
AD 1 Hippo	9.4	Control (Path) 3 Temporal Ctx	6.5
AD 2 Hippo	24.8	Control (Path) 4 Temporal Ctx	25.0
AD 3 Hippo	6.3	AD 1 Occipital Ctx	15.7
AD 4 Hippo	7.6	AD 2 Occipital Ctx (Missing)	0.0
AD 5 Hippo	53.2	AD 3 Occipital Ctx	6.8
AD 6 Hippo	24.1	AD 4 Occipital Ctx	33.2
Control 2 Hippo	40.9	AD 5 Occipital Ctx	51.8
Control 4 Hippo	6.7	AD 6 Occipital Ctx	15.3
Control (Path) 3 Hippo	5.6	Control 1 Occipital Ctx	7.6
AD 1 Temporal Ctx	19.1	Control 2 Occipital Ctx	46.0
AD 2 Temporal Ctx	34.9	Control 3 Occipital Ctx	16.6
AD 3 Temporal Ctx	5.6	Control 4 Occipital Ctx	8.5
AD 4 Temporal Ctx	25.3	Control (Path) 1 Occipital Ctx	90.1
AD 5 Inf Temporal Ctx	100.0	Control (Path) 2 Occipital Ctx	11.5
AD 5 Sup Temporal Ctx	32.5	Control (Path) 3 Occipital Ctx	3.8
AD 6 Inf Temporal Ctx	44.1	Control (Path) 4 Occipital Ctx	11.9
AD 6 Sup Temporal Ctx	32.5	Control 1 Parietal Ctx	9.5
Control 1 Temporal Ctx	10.5	Control 2 Parietal Ctx	40.6
Control 2 Temporal Ctx	45.4	Control 3 Parietal Ctx	18.3
Control 3 Temporal Ctx	28.9	Control (Path) 1 Parietal Ctx	74.2
Control 3 Temporal Ctx	10.1	Control (Path) 2 Parietal Ctx	27.5
Control (Path) 1 Temporal Ctx	65.1	Control (Path) 3 Parietal Ctx	5.0
Control (Path) 2 Temporal Ctx	36.1	Control (Path) 4 Parietal Ctx	36.3

[1033]

TABLE AGC
General_screening_panel_v1.5
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag5219,		Ag5219,
	Run		Run
Tissue Name	228758224	issue Name	228758224
Adipose	0.3	Renal ca. TK-10	0.4
Melanoma* Hs688(A).T	0.0	Bladder	0.2
Melanoma* Hs688(B).T	0.0	Gastric ca. (liver met.) NCI-N87	6.6
Melanoma* M14	0.0	Gastric ca. KATO III	0.0
Melanoma* LOXIMVI	0.5	Colon ca. SW-948	0.1
Melanoma* SK-MEL-5	0.8	Colon ca. SW480	0.6
Squamous cell carcinoma SCC-4	0.8	Colon ca.* (SW480 met) SW620	1.1
Testis Pool	0.4	Colon ca. HT29	0.0
Prostate ca.* (bone met) PC-3	2.1	Colon ca. HCT-116	1.7
Prostate Pool	0.5	Colon ca. CaCo-2	0.7
Placenta	0.0	Colon cancer tissue	0.0
Uterus Pool	0.2	Colon ca. SW1116	0.0
Ovarian ca. OVCAR-3	1.0	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	0.9	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	0.0	Colon Pool	0.7
Ovarian ca. OVCAR-5	0.2	Small Intestine Pool	0.7
Ovarian ca. IGROV-1	0.0	Stomach Pool	1.4
Ovarian ca. OVCAR-8	0.1	Bone Marrow Pool	0.1
Ovary	0.1	Fetal Heart	0.6
Breast ca. MCF-7	0.0	Heart Pool	0.3
Breast ca. MDA-MB-231	0.5	Lymph Node Pool	1.1
Breast ca. BT 549	0.0	Fetal Skeletal Muscle	0.1
Breast ca. T47D	0.0	Skeletal Muscle Pool	0.7
Breast ca. MDA-N	0.0	Spleen Pool	1.4
Breast Pool	2.6	Thymus pool	0.4
Trachea	0.4	CNS cancer (glio/astro) U87-MG	1.0
Lung	0.2	CNS cancer (glio/astro) U-118-MG	0.1
Fetal Lung	0.8	CNS cancer (neuro; met) SK-N-AS	1.4
Lung ca. NCI-N417	0.1	CNS cancer (astro) SF-539	0.0
Lung ca. LX-1	4.5	CNS cancer (astro) SNB-75	0.0
Lung ca. NCI-H146	1.1	CNS cancer (glio) SNB-19	0.0
Lung ca. SHP-77	3.3	CNS cancer (glio) SF-295	0.0
Lung ca. A549	0.0	Brain (Amygdala) Pool	60.3
Lung ca. NCI-H526	0.3	Brain (cerebellum)	100.0
Lung ca. NCI-H23	0.4	Brain (fetal)	66.4
Lung ca. NCI-H460	0.9	Brain (Hippocampus) Pool	43.5
Lung ca. HOP-62	0.0	Cerebral Cortex Pool	80.1
Lung ca. NCI-H522	0.7	Brain (Substantia nigra) Pool	54.0
Liver	0.0	Brain (Thalamus) Pool	94.6
Fetal Liver	0.4	Brain (whole)	65.1
Liver ca. HepG2	0.9	Spinal Cord Pool	36.6
Kidney Pool	1.5	Adrenal Gland	0.6
Fetal Kidney	0.7	Pituitary gland Pool	0.9
Renal ca. 786-0	0.0	Salivary Gland	0.2
Renal ca. A498	0.0	Thyroid (female)	0.0
Renal ca. ACHN	1.0	Pancreatic ca. CAPAN2	0.1
Renal ca. UO-31	0.5	Pancreas Pool	0.9

[1034]

TABLE AGD
Panel 4.1D
	Rel.		Rel.
	Exp (%)		Exp. (%)
	Ag5219,		Ag5219,
	Run		Run
Tissue Name	229739298	Tissue Name	229739298
Secondary Th1 act	0.0	HUVEC IL-1beta	3.3
Secondary Th2 act	3.2	HUVEC IFN gamma	14.0
Secondary Tr1 act	0.0	HUVEC TNF alpha + IFN gamma	2.9
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	1.8
Secondary Th2 rest	0.0	HUVEC IL-11	21.8
Secondary Tr1 rest	2.9	Lung Microvascular EC none	100.0
Primary Th1 act	0.0	Lung Microvascular EC TNF alpha + IL-1beta	31.9
Primary Th2 act	5.8	Microvascular Dermal EC none	0.0
Primary Tr1 act	0.0	Microsvasular Dermal EC	15.5
		TNF alpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium TNF alpha + IL1beta	0.0
Primary Th2 rest	1.8	Small airway epithelium none	0.0
Primary Tr1 rest	4.7	Small airway epithelium TNF alpha + IL-1beta	3.4
CD45RA CD4 lymphocyte act	0.0	Coronery artery SMC rest	2.3
CD45RO CD4 lymphocyte act	11.1	Coronery artery SMC TNF alpha + IL-1beta	0.0
CD8 lymphocyte act	6.7	Astrocytes rest	0.0
Secondary CD8 lymphocyte rest	5.9	Astrocytes TNF alpha + IL-1beta	3.4
Secondary CD8 lymphocyte act	0.0	KU-812 (Basophil) rest	4.1
CD4 lymphocyte none	3.3	KU-812 (Basophil)	26.1
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	5.9	CCD1106 (Keratinocytes) none	4.5
CH11
LAK cells rest	3.0	CCD1106 (Keratinocytes)	0.0
		TNF alpha + IL-1beta
LAK cells IL-2	2.0	Liver cirrhosis	0.0
LAK cells IL-2 + IL-12	0.0	NCI-H292 none	18.2
LAK cells IL-2 + IFN gamma	3.0	NCI-H292 IL-4	16.7
LAK cells IL-2 + IL-18	2.7	NCI-H292 IL-9	25.0
LAK cells PMA/ionomycin	0.0	NCI-H292 IL-13	48.3
NK Cells IL-2 rest	24.1	NCI-H292 IFN gamma	19.9
Two Way MLR 3 day	3.5	HPAEC none	8.1
Two Way MLR 5 day	1.5	HPAEC TNF alpha + IL-1beta	7.8
Two Way MLR 7 day	0.0	Lung fibroblast none	0.0
PBMC rest	0.0	Lung fibroblast TNF alpha + IL-1	2.0
		beta
PBMC PWM	1.0	Lung fibroblast IL-4	7.9
PBMC PHA-L	0.0	Lung fibroblast IL-9	0.0
Ramos (B cell) none	18.2	Lung fibroblast IL-13	0.0
Ramos (B cell) ionomycin	59.9	Lung fibroblast IFN gamma	2.8
B lymphocytes PWM	4.2	Dermal fibroblast CCD1070 rest	0.0
B lymphocytes CD40L and IL-4	13.2	Dermal fibroblast CCD1070 TNF	0.0
		alpha
EOL-1 dbcAMP	0.0	Dermal fibroblast CCD1070 IL-1	6.7
		beta
EOL-1 dbcAMP	4.8	Dermal fibroblast IFN gamma	40.6
PMA/ionomycin
Dendritic cells none	4.4	Dermal fibroblast IL-4	25.0
Dendritic cells LPS	0.0	Dermal fibroblasts rest	2.1
Dendritic cells anti-CD40	0.0	Neutrophils TNFa + LPS	0.0
Monocytes rest	0.0	Neutrophils rest	0.0
Monocytes LPS	0.0	Colon	0.0
Macrophages rest	0.0	Lung	0.0
Macrophages LPS	0.0	Thymus	0.0
HUVEC none	1.7	Kidney	11.3
HUVEC starved	28.1

[1035] CNS_neurodegeneration_v1.0 Summary: Ag5219 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 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.

[1036] General_screening13 panel_v1.5 Summary: Ag5219 Highest expression of this gene is deted in cerebellum (CT=27). High expression of this gene is mainly seen in all the region of 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.

[1037] In addition, moderate to low levels of expression of this gene is also seen in a number of cancer cell lines derived from brain, colon, gastric, lung, ovarian, and prostate cancers, squamous cell carcinoma and melanoma. Therefore, therapeutic modulation of this gene may be useful in the treatment of these cancers.

[1038] Low levels of expression of this gene is also seen in tissues with metabolic/endocrine functions including pancreas, adrenal and pituitary cancers, fetal heart, skeletal muscle and 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.

[1039] Panel 4.1D Summary: Ag5219 Highest expression of this gene is detected in lung microvascular endothelial cells (CT=32.4). This gene is expressed at lower levels in cytokine activated lung microvascular cells, activated dermal fibroblasts, resting and activated mucoepidermoid NCI-H292, activated basophils, starved and I-11 stimulated HVEC cells, Ramos B cells, and resting IL-2 treated NK cells. Therefore, therapeutic modulation of this gene may be useful in the treatment of autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.

[1040] AH. CG151014-02 and CG151014-03: Metabotropic Glutamate Receptor 3.

[1041] Expression of gene CG151014-02 and CG151014-02 was assessed using the primer-probe set Ag5220, described in Table AHA. Results of the RTQ-PCR runs are shown in Tables AHB and AHC. Please note that CG151014-03 represents a full-length physical clone.

TABLE AHA
Probe Name Ag5220
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-atcaacttcacgggtgcag-3′	19	1399	384
Probe	TET-5′-ctttgtggtcttgggctgtttgtttg-3′-TAMRA	26	1453	385
Reverse	5′-caggatgatgtgaaccttgg-3′	20	1482	386

[1042]

TABLE AHB
CNS_neurodegeneration_v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag5220,		Ag5220,
	Run		Run
Tissue Name	228020422	issue Name	228020422
AD 1 Hippo	2.0	Control (Path) 3 Temporal Ctx	5.8
AD 2 Hippo	49.0	Control (Path) 4 Temporal Ctx	25.2
AD 3 Hippo	1.0	AD 1 Occipital Ctx	5.6
AD 4 Hippo	13.5	AD 2 Occipital Ctx (Missing)	0.0
AD 5 hippo	35.4	AD 3 Occipital Ctx	3.1
AD 6 Hippo	59.9	AD 4 Occipital Ctx	24.7
Control 2 Hippo	34.2	AD 5 Occipital Ctx	17.2
Control 4 Hippo	7.0	AD 6 Occipital Ctx	61.6
Control (Path) 3 Hippo	4.4	Control 1 Occipital Ctx	2.6
AD 1 Temporal Ctx	6.0	Control 2 Occipital Ctx	43.2
AD 2 Temporal Ctx	39.2	Control 3 Occipital Ctx	10.2
AD 3 Temporal Ctx	2.4	Control 4 Occipital Ctx	9.0
AD 4 Temporal Ctx	29.9	Control (Path) 1 Occipital Ctx	100.0
AD 5 Inf Temporal Ctx	76.3	Control (Path) 2 Occipital Ctx	7.7
AD 5 SupTemporal Ctx	29.9	Control (Path) 3 Occipital Ctx	2.1
AD 6 Inf Temporal Ctx	60.3	Control (Path) 4 Occipital Ctx	14.2
AD 6 Sup Temporal Ctx	69.3	Control 1 Parietal Ctx	7.0
Control 1 Temporal Ctx	13.2	Control 2 Parietal Ctx	24.3
Control 2 Temporal Ctx	52.9	Control 3 Parietal Ctx	15.4
Control 3 Temporal Ctx	23.3	Control (Path) 1 Parietal Ctx	89.5
Control 4 Temporal Ctx	11.7	Control (Path) 2 Parietal Ctx	15.2
Control (Path) 1 Temporal Ctx	87.1	Control (Path) 3 Parietal Ctx	6.4
Control (Path) 2 Temporal Ctx	59.0	Control (Path) 4 Parietal Ctx	33.0

[1043]

TABLE AHC
General_screening_panel_v1.5
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag5220,		Ag5220,
	Run		Run
Tissue Name	228758228	issue Name	228758228
Adipose	0.0	Renal ca. TK-10	0.0
Melanoma* Hs688(A).T	0.0	Bladder	0.0
Melanoma* Hs688(B).T	0.0	Gastric ca. (liver met.) NCI-N87	0.0
Melanoma* M14	0.0	Gastric ca. KATO III	0.0
Melanoma* LOXIMVI	0.0	Colon ca. SW-948	0.0
Melanoma* SK-MEL-5	0.0	Colon ca. SW480	0.0
Squamous cell carcinoma SCC-4	0.0	Colon ca.* (SW480 met) SW620	0.0
Testis Pool	0.0	Colon ca. HT29	0.0
Prostate ca.* (bone met) PC-3	0.0	Colon ca. HCT-116	0.0
Prostate Pool	0.0	Colon ca. CaCo-2	0.0
Placenta	0.0	Colon cancer tissue	0.0
Uterus Pool	0.0	Colon ca. SW1116	0.0
Ovarian ca. OVCAR-3	0.0	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	0.0	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	0.0	Colon Pool	0.0
Ovarian ca. OVCAR-5	0.0	Small Intestine Pool	0.0
Ovarian ca. IGROV-1	0.0	Stomach Pool	1.6
Ovarian ca. OVCAR-8	0.0	Bone Marrow Pool	0.0
Ovary	0.0	Fetal Heart	0.0
Breast ca. MCF-7	0.0	Heart Pool	0.0
Breast ca. MDA-MB-231	0.0	Lymph Node Pool	0.7
Breast ca. BT 549	0.0	Fetal Skeletal Muscle	0.0
Breast ca. T47D	0.0	Skeletal Muscle Pool	0.0
Breast ca. MDA-N	0.0	Spleen Pool	0.0
Breast Pool	2.3	Thymus Pool	0.0
Trachea	0.0	CNS cancer (glio/astro) U87-MG	0.0
Lung	0.0	CNS cancer (glio/astro) U-118-MG	0.0
Fetal Lung	0.0	CNS cancer (neuro; met) SK-N-AS	0.0
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-539	0.0
Lung ca. LX-1	0.0	CNS cancer (astro) SNB-75	0.0
Lung ca. NCI-H146	0.0	CNS cancer (glio) SNB-19	0.0
Lung ca. SHP-77	0.0	CNS cancer (glio) SF-295	0.0
Lung ca. A549	0.0	Brain (Amygdala) Pool	75.8
Lung ca. NCI-H526	0.0	Brain (cerebellum)	100.0
Lung ca. NCI-H23	0.0	Brain (fetal)	69.3
Lung ca. NCI-H460	0.2	Brain (Hippocampus) Pool	53.2
Lung ca. HOP-62	0.0	Cerebral Cortex Pool	72.2
Lung ca. NCI-H522	0.0	Brain (Substantia nigra) Pool	80.7
Liver	0.0	Brain (Thalamus) Pool	96.6
Fetal Liver	0.0	Brain (whole)	78.5
Liver ca. HepG2	0.0	Spinal Cord Pool	25.0
Kidney Pool	0.0	Adrenal Gland	4.3
Fetal Kidney	0.5	Pituitary gland Pool	0.0
Renal ca. 786-0	0.0	Salivary Gland	0.0
Renal ca. A498	0.0	Thyroid (female)	0.0
Renal ca. ACHN	0.0	Pancreatic ca. CAPAN2	0.0
Renal ca. UO-31	0.0	Pancreas Pool	0.0

[1044] CNS_neurodegeneration_v1.0 Summary: Ag5220 This panel confirms the expression of this gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.5 for a discussion of this gene in treatment of central nervous system disorders.

[1045] General_screen_panel_v1.5 Summary: Ag5220 Highest expression of this gene is deted in cerebellum (CT=27). High expression of this gene is mainly seen in all the region of 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.

[1046] Panel 4.1D Summary: Ag5220 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[1047] AI. CG151297-01: Calmodulin-Dependent Phosphodiesterase.

[1048] Expression of gene CG151297-01 was assessed using the primer-probe set Ag7165, described in Table AIA. Results of the RTQ-PCR runs are shown in Table AIB. Please note that CG151297-01 represents a full-length physical clone.

TABLE AIA
Probe Name Ag7165
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-agaatgtaccgaaaaacattttctct-3′	26	481	387
Probe	TET-5′-ttcctcttatagaggaagcctcaaaagccg-3′-TAMRA	30	536	388
Reverse	5′-tgcttgccacataggaagaa-3′	20	570	389

[1049]

TABLE AIB
Panel 4.1D
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag7165,		Ag7165,
	Run		Run
Tissue Name	307719896	Tissue Name	307719896
Secondary Th1 act	0.0	HUVEC IL-1beta	0.0
Secondary Th2 act	0.0	HUVEC IFN gamma	0.0
Secondary Tr1 act	0.0	HUVEC TNF alpha + IFN gamma	0.0
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	0.0
Secondary Th2 rest	0.0	HUVEC IL-11	0.0
Secondary Tr1 rest	0.0	Lung Microvascular EC none	0.0
Primary Th1 act	0.0	Lung Microvascular EC TNF alpha + IL-1beta	0.0
Primary Th2 act	0.0	Microvascular Dermal EC none	0.0
Primary Tr1 act	0.0	Microsvasular Dermal EC	0.0
		TNF alpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium TNF alpha + IL1beta	0.0
Primary Th2 rest	0.0	Small airway epithelium none	0.0
Primary Tr1 rest	0.0	Small airway epithelium TNF alpha + IL-1beta	0.0
CD45RA CD4 lymphocyte act	0.0	Coronery artery SMC rest	0.0
CD45RO CD4 lymphocyte act	0.0	Coronery artery SMC TNF alpha +IL-1beta	0.0
CD8 lymphocyte act	0.0	Astrocytes rest	0.0
Secondary CD8 lymphocyte rest	0.0	Astrocytes TNF alpha + IL-1beta	0.0
Secondary CD8 lymphocyte act	0.0	KU-812 (Basophil) rest	0.0
CD4 lymphocyte none	0.0	KU-812 (Basophil)	0.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	0.0	CCD1106 (Keratinocytes) none	0.0
CH11
LAK cells rest	0.0	CCD1106 (Keratinocytes)	0.0
		TNF alpha + IL-1beta
LAK cells IL-2	0.0	Liver cirrhosis	100.0
LAK cells IL-2 + IL-12	0.0	NCI-H292 none	0.0
LAK cells IL-2 + IFN gamma	0.0	NCI-H292 IL-4	0.0
LAK cells IL-2 + IL-18	0.0	NCI-H292 IL-9	0.0
LAK cells PMA/ionomycin	0.0	NCI-H292 IL-13	0.0
NK Cells IL-2 rest	0.0	NCI-H292 IFN gamma	0.0
Two Way MLR 3 day	0.0	HPAEC none	0.0
Two Way MLR 5 day	0.0	HPAEC TNF alpha + IL-1beta	0.0
Two Way MLR 7 day	0.0	Lung fibroblast none	0.0
PBMC rest	0.0	Lung fibroblast TNF alpha + IL-1	0.0
		beta
PBMC PWM	0.0	Lung fibroblast IL-4	0.0
PBMC PHA-L	0.0	Lung fibroblast IL-9	0.0
Ramos (B cell) none	0.0	Lung fibroblast IL-13	0.0
Ramos (B cell) ionomycin	0.0	Lung fibroblast IFN gamma	0.0
B lymphocytes PWM	0.0	Dermal fibroblast CCD1070 rest	0.0
B lymphocytes CD40L and IL-4	0.0	Dermal fibroblast CCD1070 TNF	0.0
		alpha
EOL-1 dbcAMP	0.0	Dermal fibroblast CCD1070 IL-1	0.0
		beta
EOL-1 dbcAMP	0.0	Dermal fibroblast IFN gamma	0.0
PMA/ionomycin
Dendritic cells none	0.0	Dermal fibroblast IL-4	0.0
Dendritic cells LPS	0.0	Dermal Fibroblasts rest	0.0
Dendritic cells anti-CD40	0.0	Neutrophils TNFa + LPS	0.0
Monocytes rest	0.0	Neutrophils rest	0.0
Monocytes LPS	0.0	Colon	0.0
Macrophages rest	0.0	Lung	0.0
Macrophages LPS	0.0	Thymus	0.0
HUVEC none	0.0	Kidney	0.0
HUVEC starved	0.0

[1050] CNS_neurodegeneration_v1.0 Summary: Ag7165 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[1051] Panel 4.1D Summary: Ag7165 Moderate level of expression of this gene is detected mainly in the liver cirrhosis sample (CT=31.5). The presence of this gene in liver cirrhosis (a component of which involves liver inflammation and fibrosis) suggests that antibodies to the protein encoded by this gene could also be used for the diagnosis of liver cirrhosis. Furthermore, therapeutic agents involving this gene may be useful in reducing or inhibiting the inflammation associated with fibrotic and inflammatory diseases.

[1052] AJ. CG152256-01: Phosphatidylserine Synthase.

[1053] Expression of gene CG152256-01 was assessed using the primer-probe set Ag6718, described in Table AJA. Results of the RTQ-PCR runs are shown in Tables AJB, AJC and AJD.

TABLE AJA
Probe Name Ag6718
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-gagcctcgcttccgattat-3′	19	2012	390
Probe	TET-5′-tcccttcccaatattattcatccaga-3′-TAMRA	26	2031	391
Reverse	5′-ctctagcaggtttgcttttgtg-3′	22	2070	392

[1054]

TABLE AJB
CNS_neurodegeneration_v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag6718,		Ag6718,
	Run		Run
Tissue Name	276596848	issue Name	276596848
AD 1 Hippo	19.8	Control (Path) 3 Temporal Ctx	2.6
AD 2 Hippo	26.6	Control (Path) 4 Temporal Ctx	15.3
AD 3 Hippo	4.3	AD 1 Occipital Ctx	9.9
AD 4 Hippo	3.7	AD 2 Occipital Ctx (Missing)	0.0
AD 5 Hippo	58.6	AD 3 Occipital Ctx	7.1
AD 6 Hippo	45.4	AD 4 Occipital Ctx	15.9
Control 2 Hippo	28.5	AD 5 Occipital Ctx	26.6
Control 4 Hippo	8.4	AD 6 Occipital Ctx	15.1
Control (Path) 3 Hippo	3.1	Control 1 Occipital Ctx	3.6
AD 1 Temporal Ctx	4.8	Control 2 Occipital Ctx	67.4
AD 2 Temporal Ctx	24.7	Control 3 Occipital Ctx	31.2
AD 3 Temporal Ctx	7.5	Control 4 Occipital Ctx	1.8
AD 4 Temporal Ctx	10.5	Control (Path) 1 Occipital Ctx	100.0
AD 5 Inf Temporal Ctx	62.9	Control (Path) 2 Occipital Ctx	9.5
AD 5 Sup Temporal Ctx	46.3	Control (Path) 3 Occipital Ctx	5.3
AD 6 Inf Temporal Ctx	43.5	Control (Path) 4 Occipital Ctx	10.0
AD6 Sup Temporal Ctx	43.2	Control 1 Parietal Ctx	3.8
Control 1 Temporal Ctx	4.1	Control 2 Parietal Ctx	27.9
Control 2 Temporal Ctx	59.0	Control 3 Parietal Ctx	15.0
Control 3 Temporal Ctx	17.6	Control (Path) 1 Parietal Ctx	89.5
Control 3 Temporal Ctx	5.0	Control (Path) 2 Parietal Ctx	10.2
Control (Path) 1 Temporal Ctx	57.0	Control (Path) 3 Parietal Ctx	7.0
Control (Path) 2 Temporal Ctx	30.4	Control (Path) 4 Parietal Ctx	27.9

[1055]

TABLE AJC
General_screening_panel v1.6
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag6718,		Ag6718,
	Run		Run
Tissue Name	277223813	issue Name	277223813
Adipose	2.3	Renal ca. TK-10	34.4
Melanoma* Hs688(A).T	16.4	Bladder	22.2
Melanoma* Hs688(B).T	20.0	Gastric ca. (liver met.) NCI-N87	54.0
Melanoma* M14	30.6	Gastric ca. KATO III	48.3
Melanoma* LOXIMVI	55.1	Colon ca. SW-948	31.0
Melanoma* SK-MEL-5	81.8	Colon ca. SW480	87.1
Squamous cell carcinoma SCC-4	23.5	Colon ca.* (SW480 met) SW620	69.7
Testis Pool	5.2	Colon ca. HT29	0.0
Prostate ca.* (bone met) PC-3	100.0	Colon ca. HCT-116	51.4
Prostate Pool	1.8	Colon ca. CaCo-2	15.9
Placenta	2.6	Colon cancer tissue	23.5
Uterus Pool	0.8	Colon ca. SW1116	25.0
Ovarian ca. OVCAR-3	27.4	Colon ca. Colo-205	21.9
Ovarian ca. SK-OV-3	29.9	Colon ca. SW-48	24.1
Ovarian ca. OVCAR-4	33.0	Colon Pool	12.4
Ovarian ca. OVCAR-5	59.9	Small Intestine Pool	4.8
Ovarian ca. IGROV-1	47.6	Stomach Pool	1.8
Ovarian ca. OVCAR-8	32.8	Bone Marrow Pool	0.0
Ovary	11.7	Fetal Heart	14.2
Breast ca. MCF-7	18.9	Heart Pool	11.6
Breast ca. MDA-MB-231	48.0	Lymph Node Pool	3.8
Breast ca. BT 549	31.6	Fetal Skeletal Muscle	3.3
Breast ca. T47D	3.6	Skeletal Muscle Pool	0.0
Breast ca. MDA-N	17.9	Spleen Pool	2.0
Breast Pool	7.0	Thymus pool	11.7
Trachea	9.2	CNS cancer (glio/astro) U87-MG	32.3
Lung	2.4	CNS cancer (glio/astro) U-118-MG	43.2
Fetal Lung	4.9	CNS cancer (neuro; met) SK-N-AS	25.9
Lung ca. NCI-N417	15.0	CNS cancer (astro) SF-539	29.5
Lung ca. LX-1	17.6	CNS cancer (astro) SNB-75	59.0
Lung ca. NCI-H146	23.7	CNS cancer (glio) SNB-19	29.7
Lung ca. SHP-77	53.2	CNS cancer (glio) SF-295	59.5
Lung ca. A549	28.3	Brain (Amygdala) Pool	10.4
Lung ca. NCI-H526	24.3	Brain (cerebellum)	34.4
Lung ca. NCI-H23	71.7	Brain (fetal)	17.3
Lung ca. NCI-H460	14.2	Brain (Hippocampus) Pool	9.4
Lung ca. HOP-62	32.3	Cerebral Cortex Pool	7.4
Lung ca. NCI-H522	16.4	Brain (Substantia nigra) Pool	3.9
Liver	1.0	Brain (Thalamus) Pool	6.9
Fetal Liver	2.3	Brain (whole)	6.5
Liver ca. HepG2	19.2	Spinal Cord Pool	5.6
Kidney Pool	15.2	Adrenal Gland	10.3
Fetal Kidney	4.1	Pituitary gland Pool	1.1
Renal ca. 786-0	61.6	Salivary Gland	3.2
Renal ca. A498	5.6	Thyroid (female)	11.5
Renal ca. ACHN	24.7	Pancreatic ca. CAPAN2	28.1
Renal ca. UO-31	33.9	Pancreas Pool	8.3

[1056]

TABLE AJD
Panel 4.1D
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag6718,		Ag6718,
	Run		Run
Tissue Name	276596888	Tissue Name	276596888
Secondary Th1 act	51.4	HUVEC IL-1beta	18.0
Secondary Th2 act	39.5	HUVEC IFN gamma	16.5
Secondary Tr1 act	19.3	HUVEC TNF alpha + IFN gamma	4.5
Secondary Th1 rest	5.3	HUVEC TNF alpha + IL4	3.1
Secondary Th2 rest	4.5	HUVEC IL-11	0.0
Secondary Tr1 rest	5.9	Lung Microvascular EC none	13.9
Primary Th1 act	3.5	Lung Microvascular EC TNF alpha + IL-1beta	0.7
Primary Th2 act	20.7	Microvascular Dermal EC none	3.0
Primary Tr1 act	12.8	Microsvasular Dermal EC	1.2
		TNF alpha + IL-1beta
Primary Th1 rest	1.6	Bronchial epithelium TNF alpha + IL1beta	5.8
Primary Th2 rest	5.8	Small airway epithelium none	6.3
Primary Tr1 rest	0.7	Small airway epithelium TNF alpha + IL-1beta	9.7
CD45RA CD4 lymphocyte act	26.4	Coronery artery SMC rest	7.1
CD45RO CD4 lymphocyte act	30.8	Coronery artery SMC TNF alpha + IL-1beta	8.4
CD8 lymphocyte act	7.6	Astrocytes rest	3.3
Secondary CD8 lymphocyte rest	6.3	Astrocytes TNF alpha + IL-1beta	2.9
Secondary CD8 lymphocyte act	1.5	KU-812 (Basophil) rest	44.8
CD4 lymphocyte none	3.6	KU-812 (Basophil)	28.1
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	2.9	CCD1106 (Keratinocytes) none	27.5
CH11
LAK cells rest	4.5	CCD1106 (Keratinocytes)	5.1
		TNF alpha + IL-1beta
LAK cells IL-2	9.9	Liver cirrhosis	0.8
LAK cells IL-2 + IL-12	0.7	NCI-H292 none	8.0
LAK cells IL-2 + IFN gamma	4.2	NCI-H292 IL-4	10.2
LAK cells IL-2 + IL-18	1.4	NCI-H292 IL-9	19.2
LAK cells PMA/ionomycin	18.7	NCI-H292 IL-13	14.8
NK Cells IL-2 rest	21.0	NCI-H292 IFN gamma	6.8
Two Way MLR 3 day	7.6	HPAEC none	3.7
Two Way MLR 5 day	5.2	HPAEC TNF alpha + IL-1beta	8.5
Two Way MLR 7 day	4.3	Lung fibroblast none	6.8
PBMC rest	1.4	Lung fibroblast TNF alpha + IL-1	1.9
		beta
PBMC PWM	3.0	Lung fibroblast IL-4	6.1
PBMC PHA-L	4.1	Lung fibroblast IL-9	10.0
Ramos (B cell) none	42.9	Lung fibroblast IL-13	7.7
Ramos (B cell) ionomycin	22.1	Lung fibroblast IFN gamma	16.4
B lymphocytes PWM	10.8	Dermal fibroblast CCD1070 rest	33.9
B lymphocytes CD40L and IL-4	12.2	Dermal fibroblast CCD1070 TNF	100.0
		alpha
EOL-1 dbcAMP	39.0	Dermal fibroblast CCD1070 IL-1	17.4
		beta
EOL-1 dbcAMP	14.1	Dermal fibroblast IFN gamma	6.7
PMA/ionomycin
Dendritic cells none	13.5	Dermal fibroblast IL-4	10.4
Dendritic cells LPS	2.5	Dermal Fibroblasts rest	6.9
Dendritic cells anti-CD40	4.5	Neutrophils TNFa + LPS	0.4
Monocytes rest	0.6	Neutrophils rest	0.7
Monocytes LPS	3.9	Colon	0.8
Macrophages rest	1.4	Lung	0.6
Macrophages LPS	3.8	Thymus	2.9
HUVEC none	11.1	Kidney	8.1
HUVEC starved	6.4

[1057] CNS_neurodegeneration_v1.0 Summary: Ag6718 This panel confirms the expression of this gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.6 for a discussion of this gene in treatment of central nervous system disorders.

[1058] General_screen_panel_v1.6 Summary: Ag6718 Highest expression of this gene is detected in prostate cancer PC3 cell line (CT=31.9). 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.

[1059] In addition, this gene is expressed at low levels in cerebellum and fetal brain. Therefore, therapeutic modulation of this gene product may be useful in the treatment of central nervous system disorders such as ataxia and autism.

[1060] Panel 4.1D Summary: Ag6718 Highest expression of this gene is detected in TNF alpha treated dermal fibroblasts (CT=32). Moderate to low levels of expression of this gene is detected in activated polarized, naive and memory T cells, PMA/ionomycin treated LAK cells, resting IL-2 treated NK cells, Ramos B cells, cosinophils, activated HUVEC cells, lung microvascular endothelial cells, basophils and activated mucoepidermoid NCI-H292 cells. Therefore, therapeutic modulation of this gene or its protein product may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.

[1061] AK. CG173017-01: Retinoic Acid Receptor Rxe-Beta.

[1062] Expression of gene CG173017-01 was assessed using the primer-probe set Ag7565, described in Table AKA.

TABLE AKA
Probe Name Ag7565
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-ctggacgggacgggat-3′	16	222	393
Probe	TET-5′-acatagccgtttgccagccccag-3′-TAMRA	23	261	394
Reverse	5′-cttctgtccccgcagatt-3′	18	286	395

[1063] CNS_neurodegeneration_v1.0 Summary: Ag7565 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[1064] Panel 4.1D Summary: Ag7565 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[1065] AL. CG173347-01: Novel Serum Paraoxonase/arylesterase 3.

[1066] Expression of gene CG173347-01 was assessed using the primer-probe set Ag7564, described in Table ALA.

TABLE ALA
Probe Name Ag7564
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gaaagtggctctgaagatattgatatact-3′	29	153	396
Probe	TET-5′-tcctagtgggctggcttttatctcc-3′-TAMRA	25	182	397
Reverse	5′-actccaacagacctgcagact-3′	21	207	398

[1067] CNS_neurodegeneration_v1.0 Summary: Ag7564 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[1068] Panel 4.1D Summary: Ag7564 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[1069] AM. CG56234-02: Splice Variant of PCK2.

[1070] Expression of gene CG56234-02 was assessed using the primer-probe set Ag5111, described in Table AMA. Results of the RTQ-PCR runs are shown in Tables AMB, AMC, AMD and AME.

TABLE AMA
Probe Name Ag5111
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-ctgggaggccccaga-3′	15	1377	399
Probe	TET-5′-tgtccccattgacgccatcatc-3′-TAMRA	22	1395	400
Reverse	5′-gatgatcttccctttgggtct-3′	21	1429	401

[1071]

TABLE AMB
General_screening_panel_v1.5
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag5111,		Ag5111,
	Run		Run
Tissue Name	228980587	issue Name	228980587
Adipose	2.0	Renal ca. TK-10	29.1
Melanoma* Hs688(A).T	31.9	Bladder	12.1
Melanoma* Hs688(B).T	28.3	Gastric ca. (liver met.) NCI-N87	31.4
Melanoma* M14	9.9	Gastric ca. KATO III	28.1
Melanoma* LOXIMVI	4.5	Colon ca. SW-948	17.9
Melanoma* SK-MEL-5	39.8	Colon ca. SW480	14.9
Squamous cell carcinoma SCC-4	4.7	Colon ca.* (SW480 met) SW620	29.5
Testis Pool	1.6	Colon ca. HT29	8.6
Prostate ca.* (bone met) PC-3	55.1	Colon ca. HCT-116	11.0
Prostate Pool	0.5	Colon ca. CaCo-2	44.4
Placenta	0.3	Colon cancer tissue	9.7
Uterus Pool	0.6	Colon ca. SW1116	1.4
Ovarian ca. OVCAR-3	13.6	Colon ca. Colo-205	6.6
Ovarian ca. SK-OV-3	5.3	Colon ca. SW-48	14.4
Ovarian ca. OVCAR-4	7.1	Colon Pool	0.1
Ovarian ca. OVCAR-5	34.6	Small Intestine Pool	0.6
Ovarian ca. IGROV-1	22.5	Stomach Pool	1.1
Ovarian ca. OVCAR-8	100.0	Bone Marrow Pool	0.5
Ovary	0.0	Fetal Heart	0.0
Breast ca. MCF-7	87.7	Heart Pool	0.0
Breast ca. MDA-MB-231	12.6	Lymph Node Pool	0.8
Breast ca. BT 549	75.8	Fetal Skeletal Muscle	0.6
Breast ca. T47D	10.1	Skeletal Muscle Pool	0.4
Breast ca. MDA-N	16.4	Spleen Pool	1.7
Breast Pool	0.5	Thymus Pool	0.4
Trachea	4.3	CNS cancer (glio/astro) U87-MG	18.8
Lung	0.0	CNS cancer (glio/astro) U-118-MG	9.3
Fetal Lung	2.0	CNS cancer (neuro; met) SK-N-AS	7.5
Lung ca. NCI-N417	1.8	CNS cancer (astro) SF-539	11.3
Lung ca. LX-1	8.2	CNS cancer (astro) SNB-75	48.6
Lung ca. NCI-H146	11.1	CNS cancer (glio) SNB-19	31.0
Lung ca. SHP-77	11.3	CNS cancer (glio) SF-295	32.5
Lung ca. A549	11.4	Brain (Amygdala) Pool	0.4
Lung ca. NCI-H526	1.8	Brain (cerebellum)	0.3
Lung ca. NCI-H23	83.5	Brain (fetal)	0.3
Lung ca. NCI-H460	27.0	Brain (Hippocampus) Pool	2.5
Lung ca. HOP-62	1.0	Cerebral Cortex Pool	0.4
Lung ca. NCI-H522	67.4	Brain (Substantia nigra) Pool	0.0
Liver	6.3	Brain (Thalamus) Pool	1.0
Fetal Liver	6.7	Brain (whole)	0.7
Liver ca. HepG2	24.7	Spinal Cord Pool	1.1
Kidney Pool	0.8	Adrenal Gland	1.6
Fetal Kidney	1.0	Pituitary gland Pool	0.4
Renal ca. 786-0	8.7	Salivary Gland	0.9
Renal ca. A498	1.5	Thyroid (female)	0.7
Renal ca. ACHN	9.3	Pancreatic ca. CAPAN2	12.8
Renal ca. UO-31	1.9	Pancreas Pool	0.8

[1072]

TABLE AMC
General_screening_panel_v1.6
	Rel.	Rel.	Rel.		Rel.	Rel.	Rel.
	Exp. (%)	Exp. (%)	Exp. ()		Exp. (%)	Exp. (%)	Exp. (%)
	Ag5111,	Ag5111,	Ag5111,		Ag5111,	Ag5111,	Ag5111,
	Run	Run	Run		Run	Run	Run
Tissue Name	277218717	277731246	278368614	Tissue Name	277218717	277731246	278368614
Adipose	0.5	0.0	1.5	Renal ca.	24.7	20.2	33.0
				TK-10
Melanoma*	26.1	29.5	31.6	Bladder	6.7	6.1	11.6
Hs688(A).T
Melanoma*	25.2	32.1	31.9	Gastric ca.	21.3	22.5	36.1
Hs688(B).T				(liver met.)
				NCI-N87
Melanoma*	5.6	9.7	7.5	Gastric ca.	14.6	12.2	19.2
M14				KATO III
Melanoma*	3.0	0.0	4.2	Colon ca.	18.8	16.5	23.5
LOXIMVI				SW-948
Melanoma*	28.7	57.0	39.8	Colon ca.	11.8	7.3	19.5
SK-MEL-5				SW480
Squamous cell	4.8	4.2	5.1	Colon ca.*	23.0	19.9	35.6
carcinoma				(SW480 met)
SCC-4				SW620
Testis Pool	2.0	0.0	1.4	Colon ca.	10.2	4.2	8.2
				HT29
Prostate ca.*	33.2	44.4	57.8	Colon ca.	9.6	7.6	19.9
(bone met)				HCT-116
PC-3
Prostate Pool	0.3	0.0	0.6	Colon ca.	9.4	25.0	36.9
				CaCo-2
Placenta	0.3	0.0	1.1	Colon cancer	6.0	0.0	6.6
				tissue
Uterus Pool	0.0	0.0	0.6	Colon ca.	2.3	0.0	1.7
				SW1116
Ovarian ca.	12.7	8.2	18.2	Colon ca.	5.1	4.7	5.9
OVCAR-3				Colo-205
Ovarian ca.	5.3	6.5	12.2	Colon ca.	9.0	0.0	11.6
SK-OV-3				SW-48
Ovarian ca.	4.0	5.2	5.8	Colon Pool	0.7	0.0	0.7
OVCAR-4
Ovarian ca.	31.6	24.8	34.2	Small Intestine	0.3	0.0	0.8
OVCAR-5				Pool
Ovarian ca.	19.2	12.8	27.2	Stomach Pool	1.2	0.0	2.3
IGROV- 1
Ovarian ca.	100.0	100.0	100.0	Bone Marrow	0.0	0.0	0.0
OVCAR-8				Pool
Ovary	0.0	0.0	0.2	Fetal Heart	0.0	0.0	0.3
Breast ca.	54.0	51.4	77.9	Heart Pool	0.4	0.0	0.0
MCF-7
Breast ca.	8.5	7.6	7.7	Lymph Node	1.2	0.0	0.0
MDA-MB-231				Pool
Breast ca. BT	47.0	30.4	49.0	Fetal Skeletal	0.0	0.0	0.0
549				Muscle
Breast ca. T47D	5.1	6.5	7.1	Skeletal	0.0	0.0	0.0
				Muscle Pool
Breast ca.	6.1	6.0	24.5	Spleen Pool	0.7	0.0	2.5
MDA-N
Breast Pool	0.3	0.0	0.3	Thymus Pool	0.5	0.0	1.8
Trachea	3.3	0.0	8.3	CNS cancer	12.9	7.9	13.8
				(glio/astro)
				U87-MG
Lung	0.0	0.0	0.0	CNS cancer	5.9	4.4	8.1
				(glio/astro)
				U-118-MG
Fetal Lung	0.9	0.0	2.1	CNS cancer	6.4	4.9	6.7
				(neuro; met)
				SK-N-AS
Lung ca.	1.3	0.0	3.8	CNS cancer	5.8	6.4	8.5
NCI-N417				(astro) SF-539
Lung ca. LX-1	5.5	7.8	9.5	CNS cancer	25.0	29.9	26.8
				(astro)
				SNB-75
Lung ca.	8.0	8.5	11.5	CNS cancer	23.8	20.7	29.5
NCI-H146				(glio) SNB-19
Lung ca.	12.2	14.3	21.3	CNS cancer	38.2	28.7	46.7
SHP-77				(glio) SF-295
Lung ca. A549	11.5	11.7	15.9	Brain	0.8	0.0	1.1
				(Amygdala)
				Pool
Lung ca.	1.8	0.0	1.7	Brain	1.0	0.0	1.1
NCI-H526				(cerebellum)
Lung ca.	42.6	68.8	55.1	Brain (fetal)	0.0	0.0	0.4
NCI-H23
Lung ca.	16.7	23.5	38.4	Brain	0.4	0.0	1.2
NCI-H460				(Hippocampus)
				Pool
Lung ca.	2.0	0.0	3.0	Cerebral	0.0	0.0	0.6
HOP-62				Cortex Pool
Lung ca.	41.5	64.2	87.1	Brain	0.0	0.0	0.4
NCI-H522				(Substantia
				nigra) Pool
Liver	4.4	4.6	7.1	Brain	0.0	0.0	0.0
				(Thalamus)
				Pool
Fetal Liver	5.8	3.3	8.7	Brain (whole)	6.7	0.0	2.8
Liver ca.	15.7	16.3	18.8	Spinal Cord	0.6	0.0	0.5
HepG2				Pool
Kidney Pool	0.7	0.0	0.3	Adrenal Gland	1.4	0.0	1.4
Fetal Kidney	0.9	0.0	1.0	Pituitary gland	0.0	0.0	0.7
				Pool
Renal ca. 786-0	9.3	8.1	13.8	Salivary Gland	0.8	0.0	1.8
Renal ca. A498	1.1	0.0	2.0	Thyroid	1.0	0.0	2.1
				(female)
Renal ca.	5.8	6.0	10.8	Pancreatic ca.	13.1	9.6	19.9
ACHN				CAPAN2
Renal ca.	2.4	0.0	3.3	Pancreas Pool	4.8	0.0	7.3
UO-31

[1073]

TABLE AMD
Panel 4.1D
	Rel.	Rel.		Rel.	Rel.
	Exp. (%)	Exp. (%)		Exp. (%)	Exp. (%)
	g5111,	Ag5111,		Ag5111,	Ag5111,
	Run	Run		Run	Run
Tissue Name	226444761	276596864	Tissue Name	226444761	276596864
Secondary Th1 act	90.8	58.6	HUVEC IL-1beta	18.7	10.7
Secondary Th2 act	40.9	57.8	HUVEC IFN gamma	2.8	6.2
Secondary Tr1 act	57.4	16.5	HUVEC TNF alpha + IFN	5.0	6.2
			gamma
Secondary Th1 rest	27.2	8.4	HUVEC TNF alpha + IL4	23.2	8.8
Secondary Th2 rest	6.0	0.0	HUVEC IL-11	2.3	0.0
Secondary Tr1 rest	7.2	4.0	Lung Microvascular	3.2	15.4
			EC none
Primary Th1 act	32.8	5.0	Lung Microvascular	6.4	0.0
			EC TNF alpha + IL-1beta
Primary Th2 act	49.0	19.9	Microvascular	6.6	0.0
			Dermal EC none
Primary Tr1 act	50.0	38.4	Microsvasular	0.0	0.0
			Dermal EC
			TNF alpha + IL-1beta
Primary Th1 rest	6.0	8.5	Bronchial epithelium	8.7	6.9
			TNF alpha + IL1beta
Primary Th2 rest	6.4	6.3	Small airway	2.2	0.0
			epithelium none
Primary Tr1 rest	18.0	0.0	Small airway	11.8	0.0
			epithelium TNF alpha +
			IL-1beta
CD45RA CD4	95.9	76.8	Coronery artery SMC	18.3	10.2
lymphocyte act			rest
CD45RO CD4	95.3	100.0	Coronery artery SMC	9.4	8.8
lymphocyte act			TNF alpha + IL-1beta
CD8 lymphocyte act	77.4	4.5	Astrocytes rest	2.1	0.0
Secondary CD8	90.1	17.3	Astrocytes TNF alpha +	0.0	0.0
lymphocyte rest			IL-1beta
Secondary CD8	21.0	7.7	KU-812 (Basophil)	25.9	10.2
lymphocyte act			rest
CD4 lymphocyte none	0.0	0.0	KU-812 (Basophil)	26.8	21.2
			PMA/ionomycin
2ry	5.4	0.0	CCD1106	15.2	4.9
Th1/Th2/Tr1_anti-CD95			(Keratinocytes) none
CH11
LAK cells rest	43.5	19.9	CCD1106	9.0	12.3
			(Keratinocytes)
			TNF alpha + IL-1beta
LAK cells IL-2	52.1	18.4	Liver cirrhosis	8.3	0.0
LAK cells IL-2 + IL-12	33.7	0.0	NCI-H292 none	15.3	3.4
LAK cells IL-2 + IFN	57.0	6.6	NCI-H292 IL-4	13.5	17.2
gamma
LAK cells IL-2 + IL-18	46.0	9.5	NCI-H292 IL-9	14.2	14.1
LAK cells	43.5	24.5	NCI-H292 IL-13	29.1	11.3
PMA/ionomycin
NK Cells IL-2 rest	60.7	37.4	NCI-H292 IFN	44.8	7.2
			gamma
Two Way MLR 3 day	32.1	10.3	HPAEC none	2.0	0.0
Two Way MLR 5 day	53.2	3.6	HPAEC TNF alpha + IL-1	7.2	7.0
			beta
Two Way MLR 7 day	23.5	9.6	Lung fibroblast none	21.2	15.9
PBMC rest	6.1	0.0	Lung fibroblast TNF	11.5	0.0
			alpha + IL-1beta
PBMC PWM	23.5	9.1	Lung fibroblast IL-4	2.4	0.0
PBMC PHA-L	35.8	12.2	Lung fibroblast IL-9	17.6	5.4
Ramos (B cell) none	58.6	16.7	Lung fibroblast IL-13	13.4	0.0
Ramos (B cell)	71.7	92.7	Lung fibroblast IFN	11.6	3.1
ionomycin			gamma
B lymphocytes PWM	21.6	14.8	Dermal fibroblast	99.3	64.6
			CCD1070 rest
B lymphocytes CD40L	29.7	23.2	Dermal fibroblast	74.7	88.9
and IL-4			CCD1070 TNF alpha
EOL-1 dbcAMP	32.3	32.8	Dermal fibroblast	29.9	50.0
			CCD1070 IL-1beta
EOL-1 dbcAMP	10.6	3.2	Dermal fibroblast	13.3	0.0
PMA/ionomycin			IFN gamma
Dendritic cells none	66.0	24.5	Dermal fibroblast	12.2	0.0
			IL-4
Dendritic cells LPS	31.4	0.0	Dermal Fibroblasts	0.0	0.0
			rest
Dendritic cells	48.3	28.1	Neutrophils	0.0	0.0
anti-CD40			TNFa + LPS
Monocytes rest	29.1	0.0	Neutrophils rest	0.0	0.0
Monocytes LPS	37.6	18.0	Colon	32.3	8.2
Macrophages rest	100.0	12.9	Lung	3.5	0.0
Macrophages LPS	28.1	16.2	Thymus	12.1	0.0
HUVEC none	7.9	5.7	Kidney	83.5	31.9
HUVEC starved	17.4	8.4

[1074]

TABLE AME
general oncology screening panel_v_2.4
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag5111,		Ag5111,
	Run		Run
Tissue Name	260280403	Tissue Name	260280403
Colon cancer 1	49.0	Bladder cancer NAT 2	0.0
Colon cancer NAT 1	2.5	Bladder cancer NAT 3	0.0
Colon cancer 2	11.7	Bladder cancer NAT 4	0.0
Colon cancer NAT 2	28.5	Prostate adenocarcinoma 1	5.0
Colon cancer 3	43.5	Prostate adenocarcinoma 2	0.0
Colon cancer NAT 3	53.2	Prostate adenocarcinoma 3	0.0
Colon malignant cancer 4	100.0	Prostate adenocarcinoma 4	0.0
Colon normal adjacent tissue 4	8.4	Prostate cancer NAT 5	0.0
Lung cancer 1	12.2	Prostate adenocarcinoma 6	0.0
Lung NAT 1	0.0	Prostate adenocarcinoma 7	0.0
Lung cancer 2	72.2	Prostate adenocarcinoma 8	0.0
Lung NAT 2	0.0	Prostate adenocarcinoma 9	4.0
Squamous cell carcinoma 3	18.8	Prostate cancer NAT 10	0.0
Lung NAT 3	0.0	Kidney cancer 1	7.5
metastatic melanoma 1	0.0	KidneyNAT 1	0.0
Melanoma 2	6.3	Kidney cancer 2	73.2
Melanoma 3	0.0	Kidney NAT 2	9.2
metastatic melanoma 4	0.0	Kidney cancer 3	6.3
metastatic melanoma 5	2.0	Kidney NAT 3	0.0
Bladder cancer 1	0.0	Kidney cancer 4	7.6
Bladder cancer NAT 1	0.0	Kidney NAT 4	84.1
Bladder cancer 2	0.0

[1075] CNS_neurodegeneration_v1.0 Summary: Ag5111 Expression of the CG56234-02 gene is low/undetectable in all samples on this panel (CTs>35).

[1076] General_screen_panel_v1.5 Summary: Ag5111 Highest expression of the CG56234-02 gene is seen in an ovarian cancer cell line (CT=30). This gene encodes a splice variant of PEPCK2, the rate-limiting enzyme for gluconeogenesis that has been shown to be regulated in response to hormones and environmental stress. In addition, to the ovarian cancer cell line, this gene is expressed at a moderate level in most of the cancer cell lines used in this panel. Therefore, modulation of the gene product using small molecule drugs may affect the growth and survival of cancer cells. Expression of this gene could potentially be used as a diagnostic marker of the metabolic status of cells and inhibition of activity of this gene prodcut might be used for therapeutic treatment of cancers.

[1077] This gene is also moderately expressed (CT values=34) in adult and fetal liver. Inhibition of this enzyme could potentially decrease hepatic glucose production and thus serve as an effective treatment for Type 2 diabetes, which is characterized by excess hepatic glucose production.

[1078] General_screen_panel_v1.6 Summary: Ag5111 Three experiments with the same probe and primer produce results that are in excellent agreement. Highest expression is seen in an ovarian cancer cell line (CTs=31-34) and overall, expression of this gene appears to be more highly associated with cancer cell line samples than with normal tissue samples. These results are also in agreement with results in Panel 1.5. Please see that panel for discussion of this gene.

[1079] Panel 4.1D Summary: Ag5111 This gene is expressed at low levels in a wide range of cell across this panel (CTs=33.3-34.4), including CD4 T cells (naive and memory T cells), CD8 T cells, B cells and macrophages. Expression of this transcript is also found in dermal fibroblasts and kidney. This transcript encodes a homolog of a key enzyme in glucogenesis and therefore may be important for the metabolic status of all these cell types which contribute to the inflammatory response. Therefore, modulation of the activity or expression of this putative protein by small molecules could affect the activity of these cells and be useful for the treatment of autoimmune diseases such as inflammatory bowel diseases, rheumatoid arthritis, asthma, COPD, psoriasis and lupus.

[1080] General oncology screening panel_v—2.4 Summary: Ag5111 Low but significant expression is seen in a colon cancer, a kidney cancer, and a lung cancer (CTs=34-35). This is in agreement with the preferential expression in cancer cell lines seen in Panels 1.5 and 1.6. Please see Panel 1.5 for discussion of this gene in oncology.

[1081] AN. CG56836-03: Cathepsin B.

[1082] Expression of gene CG56836-03 was assessed using the primer-probe sets Ag2052 and Ag5278, described in Tables ANA, ANB and ANC. Results of the RTQ-PCR runs are shown in Tables AND, ANE, ANF, ANG, ANH, ANI, ANJ and ANK.

TABLE ANA
Probe Name Ag2052
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-gtcccaccatcaaagagatca-3′	21	414	402
Probe	TET-5′-agaccagggctcctgtggctcct-3′-TAMRA	23	436	403
Reverse	5′-atgcagatccggtcagagat-3′	20	485	404

[1083]

TABLE ANB
Probe Name Ag5277
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-gatctgcatccacaccaat-3′	19	390	405
Probe	TET-5′-cctgctcacctgcctgctctacaagt-3′-TAMRA	26	441	406
Reverse	5′-cagtcagtgttccaggagtt-3′	20	568	407

[1084]

TABLE ANC
Probe Name Ag5278
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-tatgaatccaatagcgaga-3′	19	653	408
Probe	TET-5′-agctttctctgtgtattcggacttcc-3′-TAMRA	26	715	409
Reverse	5′-tgttggtacactcctgactt-3′	20	749	410

[1085]

TABLE AND
AI_comprehensive panel_v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag2052,		Ag2052,
	Run		Run
Tissue Name	275804031	issue Name	275804031
110967 COPD-F	10.2	112427 Match Control Psoriasis-F	15.4
110980 COPD-F	6.4	112418 Psoriasis-M	10.4
110968 COPD-M	12.0	112723 Match Control Psoriasis-M	5.9
110977 COPD-M	14.0	112419 Psoriasis-M	12.9
110989 Emphysema-F	15.6	112424 Match Control Psoriasis-M	4.3
110992 Emphysema-F	20.0	112420 Psoriasis-M	29.7
110993 Emphysema-F	13.8	112425 Match Control Psoriasis-M	14.8
110994 Emphysema-F	6.0	104689 (MF) OA Bone-Backus	29.9
110995 Emphysema-F	33.2	104690 (MF) Adj “Normal”	15.4
		Bone-Backus
110996 Emphysema-F	8.5	104691 (MF) OA Synovium-Backus	55.9
110997 Asthma-M	6.1	104692 (BA) OA Cartilage-Backus	27.9
111001 Asthma-F	6.7	104694 (BA) OA Bone-Backus	39.5
111002 Asthma-F	11.2	104695 (BA) Adj “Normal”	23.0
		Bone-Backus
111003 Atopic Asthma-F	9.7	104696 (BA) OA Synovium-Backus	100.0
111004 Atopic Asthma-F	12.2	104700 (SS) OA Bone-Backus	12.2
111005 Atopic Asthma-F	7.4	104701 (SS) Adj “Normal”	24.3
		Bone-Backus
111006 Atopic Asthma-F	1.7	104702 (SS) OA Synovium-Backus	43.8
111417 Allergy-M	9.0	117093 OA Cartilage Rep7	18.4
112347 Allergy-M	0.0	112672 OA Bone5	17.3
112349 Normal Lung-F	0.0	112673 OA Synovium5	6.6
112357 Normal Lung-F	10.7	112674 OA Synovial Fluid cells5	8.4
112354 Normal Lung-M	3.6	117100 OA Cartilage Rep14	8.4
112374 Crohns-F	10.6	112756 OA Bone9	13.4
112389 Match Control Crohns-F	14.1	112757 OA Synovium9	4.0
112375 Crohns-F	9.9	112758 OA Synovial Fluid Cells9	5.0
112732 Match Control Crohns-F	6.6	117125 RA Cartilage Rep2	19.5
112725 Crohns-M	1.3	113492 Bone2 RA	11.7
112387 Match Control	11.7	113493 Synovium2 RA	3.6
Crohns-M
112378 Crohns-M	0.0	113494 Syn Fluid Cells RA	6.7
112390 Match Control	14.5	113499 Cartilage4 RA	6.7
Crohns-M
112726 Crohns-M	11.5	113500 Bone4 RA	6.3
112731 Match Control	7.5	113501 Synovium4 RA	5.1
Crohns-M
112380 Ulcer Col-F	8.7	113502 Syn Fluid Cells4 RA	3.4
112734 Match Control Ulcer	15.4	113495 Cartilage3 RA	7.2
Col-F
112384 Ulcer Col-F	25.7	113496 Bone3 RA	7.0
112737 Match Control Ulcer	4.1	113497 Synovium3 RA	4.4
Col-F
112386 Ulcer Col-F	7.1	113498 Syn Fluid Cells3 RA	9.7
112738 Match Control Ulcer	13.1	117106 Normal Cartilage Rep20	8.1
Col-F
112381 Ulcer Col-M	0.1	113663 Bone3 Normal	0.0
112735 Match Control Ulcer	0.4	113664 Synovium3 Normal	0.0
Col-M
112382 Ulcer Col-M	12.9	113665 Syn Fluid Cells3 Normal	0.0
112394 Match Control Ulcer	3.3	117107 Normal Cartilage Rep22	3.2
Col-M
112383 Ulcer Col-M	30.4	113667 Bone4 Normal	6.3
112736 Match Control Ulcer	11.0	113668 Synovium4 Normal	8.1
Col-M
112423 Psoriasis-F	5.5	113669 Syn Fluid Cells4 Normal	12.9

[1086]

TABLE ANE
General_screening_panel_v1.5
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag5278,		Ag5278,
	Run		Run
Tissue Name	230509757	issue Name	230509757
Adipose	0.2	Renal ca. TK-10	6.2
Melanoma* Hs688(A).T	24.0	Bladder	5.1
Melanoma* Hs688(B).T	12.9	Gastric ca. (liver met.) NCI-N87	9.7
Melanoma* M14	51.8	Gastric ca. KATO III	5.7
Melanoma* LOXIMVI	26.6	Colon ca. SW-948	2.1
Melanoma* SK-MEL-5	17.0	Colon ca. SW480	7.0
Squamous cell carcinoma SCC-4	3.2	Colon ca.* (SW480 met) SW620	3.2
Testis Pool	0.5	Colon ca. HT29	0.7
Prostate ca.* (bone met) PC-3	0.6	Colon ca. HCT-116	2.6
Prostate Pool	0.2	Colon ca. CaCo-2	5.3
Placenta	5.4	Colon cancer tissue	14.5
Uterus Pool	0.0	Colon ca. SW1116	2.3
Ovarian ca. OVCAR-3	16.3	Colon ca. Colo-205	7.9
Ovarian ca. SK-OV-3	18.7	Colon ca. SW-48	2.7
Ovarian ca. OVCAR-4	3.9	Colon Pool	1.8
Ovarian ca. OVCAR-5	5.7	Small Intestine Pool	0.7
Ovarian ca. IGROV-1	0.3	Stomach Pool	1.2
Ovarian ca. OVCAR-8	1.3	Bone Marrow Pool	0.3
Ovary	3.2	Fetal Heart	0.5
Breast ca. MCF-7	3.0	Heart Pool	1.2
Breast ca. MDA-MB-231	4.1	Lymph Node Pool	2.9
Breast ca. BT 549	100.0	Fetal Skeletal Muscle	0.3
Breast ca. T47D	2.0	Skeletal Muscle Pool	1.0
Breast ca. MDA-N	1.6	Spleen Pool	2.1
Breast Pool	2.0	Thymus pool	1.4
Trachea	2.3	CNS cancer (glio/astro) U87-MG	8.1
Lung	0.5	CNS cancer (glio/astro) U-118-MG	12.3
Fetal Lung	2.2	CNS cancer (neuro; met) SK-N-AS	2.0
Lung ca. NCI-N417	0.1	CNS cancer (astro) SF-539	3.4
Lung ca. LX-1	6.1	CNS cancer (astro) SNB-75	27.4
Lung ca. NCI-H146	0.4	CNS cancer (glio) SNB-19	2.4
Lung ca. SHP-77	1.8	CNS cancer (glio) SF-295	26.8
Lung ca. A549	4.1	Brain (Amygdala) Pool	2.1
Lung ca. NCI-H526	0.1	Brain (cerebellum)	6.9
Lung ca. NCI-H23	3.0	Brain (fetal)	1.2
Lung ca. NCI-H460	2.6	Brain (Hippocampus) Pool	1.9
Lung ca. HOP-62	4.0	Cerebral Cortex Pool	3.8
Lung ca. NCI-H522	1.0	Brain (Substantia nigra) Pool	2.6
Liver	1.4	Brain (Thalamus) Pool	2.8
Fetal Liver	10.4	Brain (whole)	5.3
Liver ca. HepG2	8.3	Spinal Cord Pool	2.4
Kidney Pool	0.0	Adrenal Gland	3.2
Fetal Kidney	0.7	Pituitary gland Pool	0.6
Renal ca. 786-0	5.3	Salivary Gland	2.5
Renal ca. A498	4.0	Thyroid (female)	25.3
Renal ca. ACHN	3.0	Pancreatic ca. CAPAN2	5.7
Renal ca. UO-31	15.2	Pancreas Pool	3.0

[1087]

TABLE ANF
HASS Panel v1.0
	Rel.	Rel.		Rel.	Rel.
	Exp. (%)	Exp. (%)		Exp. (%)	Exp. (%)
	Ag2052,	Ag2052,		Ag2052,	Ag2052,
	Run	Run		Run	Run
Tissue Name	247736616	248455625	Tissue Name	247736616	248455625
MCF-7 C1	12.6	7.1	U87-MG F1 (B)	40.3	22.4
MCF-7 C2	12.7	8.6	U87-MG F2	11.1	6.7
MCF-7 C3	10.2	5.6	U87-MG F3	12.2	8.0
MCF-7 C4	16.2	19.5	U87-MG F4	27.0	17.8
MCF-7 C5	13.2	11.0	U87-MG F5	59.0	38.2
MCF-7 C6	13.2	14.6	U87-MG F6	61.1	44.4
MCF-7 C7	12.7	10.4	U87-MG F7	72.7	50.7
MCF-7 C9	9.7	12.9	U87-MG F8	75.3	54.7
MCF-7 C10	15.8	17.1	U87-MG F9	29.9	28.1
MCF-7 C11	2.5	1.8	U87-MG F10	65.1	50.0
MCF-7 C12	9.9	8.0	U87-MG F11	58.2	48.3
MCF-7 C13	12.5	17.1	U87-MG F12	47.0	42.6
MCF-7 C15	5.6	6.5	U87-MG F13	95.3	77.9
MCF-7 C16	14.0	21.5	U87-MG F14	96.6	80.1
MCF-7 C17	10.2	6.9	U87-MG F15	64.6	54.7
T24 D1	25.0	14.4	U87-MG F16	51.8	47.6
T24 D2	33.0	42.0	U87-MG F17	62.0	49.0
T24 D3	29.3	19.1	LnCAP A1	9.4	6.0
T24 D4	39.8	30.6	LnCAP A2	8.1	5.5
T24 D5	28.5	19.5	LnCAP A3	6.3	3.4
T24 D6	32.8	27.2	LnCAP A4	10.4	6.9
T24 D7	18.3	25.9	LnCAP A5	10.0	6.0
T24 D9	12.1	8.5	LnCAP A6	10.0	6.3
T24 D10	23.5	19.2	LnCAP A7	9.2	6.6
T24 D11	13.2	11.7	LnCAP A8	11.5	8.8
T24 D12	24.0	19.2	LnCAP A9	10.8	7.2
T24 D13	8.5	5.8	LnCAP A10	11.0	8.0
T24 D15	10.7	8.0	LnCAP A11	15.7	10.7
T24 D16	6.6	4.7	LnCAP A12	3.5	2.3
T24 D17	12.0	7.4	LnCAP A13	5.7	3.3
CAPaN B1	64.6	52.1	LnCAP A14	3.3	1.7
CAPaN B2	46.3	33.2	LnCAP A15	2.5	1.3
CAPaN B3	13.0	10.7	LnCAP A16	12.5	8.6
CAPaN B4	39.8	30.4	LnCAP A17	12.2	2.5
CAPaN B5	39.5	28.7	Primary Astrocytes	47.3	27.9
CAPaN B6	27.5	25.7	Primary Renal	100.0	100.0
			Proximal Tubule
			Epithelial cell A2
CAPaN B7	30.1	31.2	Primary melanocytes	40.1	21.8
			A5
CAPaN B8	33.2	26.8	126443-341 medullo	0.7	0.4
CAPaN B9	38.7	50.0	126444-487 medullo	2.2	1.8
CAPaN B10	57.4	51.4	126445-425 medullo	1.6	1.0
CAPaN B11	45.1	28.5	126446-690 medullo	4.4	2.6
CAPaN B12	31.4	22.7	126447-54 adult	33.4	22.2
			glioma
CAPaN B13	38.7	29.7	126448-245 adult	9.4	6.3
			glioma
CAPaN B14	29.9	22.1	126449-317 adult	10.4	6.0
			glioma
CAPaN B15	32.8	20.7	126450-212 glioma	41.5	22.8
CAPaN B16	29.7	16.4	126451-456 glioma	17.4	11.3
CAPaN B17	42.3	24.3

[1088]

TABLE ANG
Panel 1.3D
	Rel.		Rel.
	Exp. (%		Exp. (%)
	Ag2052,		Ag2052,
	Run		Run
Tissue Name	166004256	Tissue Name	166004256
Liver adenocarcinoma	21.8	Kidney (fetal)	19.2
Pancreas	4.2	Renal ca. 786-0	8.4
Pancreatic ca. CAPAN 2	24.5	Renal ca. A498	26.4
Adrenal gland	11.7	Renal ca. RXF 393	34.4
Thyroid	37.6	Renal ca. ACHN	9.3
Salivary gland	25.3	Renal ca. UO-31	33.7
Pituitary gland	13.8	Renal ca. TK-10	2.8
Brain (fetal)	11.7	Liver	14.0
Brain (whole)	51.4	Liver (fetal)	16.2
Brain (amygdala)	29.5	Liver ca. (hepatoblast) HepG2	33.9
Brain (cerebellum)	24.3	Lung	22.8
Brain (hippocampus)	24.5	Lung (fetal)	10.7
Brain (substantia nigra)	17.8	Lung ca. (small cell) LX-1	25.2
Brain (thalamus)	27.5	Lung ca. (small cell) NCI-H69	2.1
Cerebral Cortex	45.4	Lung ca. (s.cell var.) SHP-77	6.9
Spinal cord	30.4	Lung ca. (large cell)NCI-H460	2.1
glio/astro U87-MG	42.6	Lung ca. (non-sm. cell) A549	4.4
glio/astro U-118-MG	23.5	Lung ca. (non-s.cell) NCI-H23	4.4
astrocytoma SW1783	24.3	Lung ca. (non-s.cell) HOP-62	30.4
neuro*; met SK-N-AS	5.4	Lung ca. (non-s.cl) NCI-H522	3.4
astrocytoma SF-539	43.8	Lung ca. (squam.) SW 900	18.4
astrocytoma SNB-75	21.9	Lung ca. (squam.) NCI-H596	1.9
glioma SNB-19	20.7	Mammary gland	15.5
glioma U251	43.2	Breast ca.* (pl.ef) MCF-7	10.7
glioma SF-295	25.5	Breast ca.* (pl.ef) MDA-MB-231	13.2
Heart (fetal)	15.2	Breast ca.* (pl.ef) T47D	6.0
Heart	13.7	Breast ca. BT-549	100.0
Skeletal muscle (fetal)	8.2	Breast ca. MDA-N	3.7
Skeletal muscle	11.8	Ovary	23.5
Bone marrow	19.5	Ovarian ca. OVCAR-3	14.1
Thymus	7.7	Ovarian ca. OVCAR-4	20.7
Spleen	34.6	Ovarian ca. OVCAR-5	23.5
Lymph node	17.4	Ovarian ca. OVCAR-8	7.8
Colorectal	12.5	Ovarian ca. IGROV-1	5.1
Stomach	8.0	Ovarian ca.* (ascites) SK-OV-3	27.9
Small intestine	12.2	Uterus	11.0
Colon ca. SW480	9.7	Placenta	40.3
Colon ca.* SW620(SW480 met)	5.9	Prostate	8.0
Colon ca. HT29	1.2	Prostate ca.* (bone met)PC-3	8.4
Colon ca. HCT-116	4.8	Testis	4.3
Colon ca. CaCo-2	15.7	Melanoma Hs688(A).T	22.7
Colon ca. tissue(ODO3866)	62.4	Melanoma* (met) Hs688(B).T	21.8
Colon ca. HCC-2998	12.9	Melanoma UACC-62	23.0
Gastric ca.* (liver met) NCI-N87	21.9	Melanoma M14	43.2
Bladder	11.4	Melanoma LOX IMVI	11.2
Trachea	13.1	Melanoma* (met) SK-MEL-5	22.8
Kidney	31.0	Adipose	12.8

[1089]

TABLE ANH
Panel 2.2
	Rel.		Rel.
	Exp. %)		Exp. (%)
	Ag2052,		Ag2052,
	Run		Run
Tissue Name	174244470	Tissue Name	174244470
Normal Colon	3.3	Kidney Margin (OD04348)	13.1
Colon cancer (OD06064)	23.3	Kidney malignant cancer	1.0
		(OD06204B)
Colon Margin (OD06064)	3.6	Kidney normal adjacent tissue	9.5
		(OD06204E)
Colon cancer (OD06159)	1.5	Kidney Cancer (OD04450-01)	22.2
Colon Margin (OD06159)	3.6	Kidney Margin (OD04450-03)	4.5
Colon cancer (OD06297-04)	1.3	Kidney Cancer 8120613	0.6
Colon Margin (OD06297-05)	4.7	Kidney Margin 8120614	0.0
CC Gr.2 ascend colon (ODO3921)	1.5	Kidney Cancer 9010320	10.7
CC Margin (ODO3921)	2.6	Kidney Margin 9010321	6.6
Colon cancer metastasis	6.7	Kidney Cancer 8120607	9.7
(OD06104)
Lung Margin (OD06104)	6.0	Kidney Margin 8120608	11.4
Colon mets to lung (OD04451-01)	12.8	Normal Uterus	3.1
Lung Margin (OD04451-02)	6.0	Uterine Cancer 064011	3.5
Normal Prostate	2.3	Normal Thyroid	7.2
Prostate Cancer (OD04410)	0.7	Thyroid Cancer 064010	44.8
Prostate Margin (OD04410)	1.2	Thyroid Cancer A302152	100.0
Normal Ovary	6.1	Thyroid Margin A302153	7.6
Ovarian cancer (OD06283-03)	4.1	Normal Breast	2.2
Ovarian Margin (OD06283-07)	2.0	Breast Cancer (OD04566)	2.5
Ovarian Cancer 064008	9.2	Breast Cancer 1024	6.3
Ovarian cancer (OD06145)	8.9	Breast Cancer (OD04590-01)	8.5
Ovarian Margin (OD06145)	3.8	Breast Cancer Mets	4.4
		(OD04590-03)
Ovarian cancer (OD06455-03)	6.1	Breast Cancer Metastasis	3.3
		(OD04655-05)
Ovarian Margin (OD06455-07)	1.0	Breast Cancer 064006	4.9
Normal Lung	4.9	Breast Cancer 9100266	2.7
Invasive poor diff. lung adeno	2.9	Breast Margin 9100265	1.7
(ODO4945-01
Lung Margin (ODO4945-03)	3.2	Breast Cancer A209073	1.5
Lung Malignant Cancer	11.1	Breast Margin A2090734	2.3
(OD03126)
Lung Margin (OD03126)	5.1	Breast cancer (OD06083)	4.4
Lung Cancer (OD05014A)	19.6	Breast cancer node metastasis	5.6
		(OD06083)
Lung Margin (OD05014B)	15.3	Normal Liver	6.9
Lung cancer (OD06081)	3.4	Liver Cancer 1026	8.0
Lung Margin (OD06081)	1.3	Liver Cancer 1025	22.2
Lung Cancer (OD04237-01)	4.6	Liver Cancer 6004-T	13.8
Lung Margin (OD04237-02)	11.1	Liver Tissue 6004-N	4.1
Ocular Melanoma Metastasis	3.5	Liver Cancer 6005-T	21.5
Ocular Melanoma Margin (Liver)	9.8	Liver Tissue 6005-N	51.1
Melanoma Metastasis	5.4	Liver Cancer 064003	13.6
Melanoma Margin (Lung)	5.1	Normal Bladder	2.8
Normal Kidney	3.3	Bladder Cancer 1023	4.8
Kidney Ca, Nuclear grade 2	5.0	Bladder Cancer A302173	6.1
(OD04338)
Kidney Margin (OD04338)	10.6	Normal Stomach	5.3
Kidney Ca Nuclear grade 1/2	15.0	Gastric Cancer 9060397	6.3
(OD04339)
Kidney Margin (OD04339)	11.3	Stomach Margin 9060396	5.0
Kidney Ca, Clear cell type	4.2	Gastric Cancer 9060395	4.6
(OD04340)
Kidney Margin (OD04340)	7.2	Stomach Margin 9060394	7.7
Kidney Ca, Nuclear grade 3	3.1	Gastric Cancer 064005	3.8
(OD04348)

[1090]

TABLE ANI
Panel 4.1D
	Rel.		Rel.
	Exp. (%		Exp. (%)
	Ag5278,		Ag5278,
	Run		Run
Tissue Name	230472911	Tissue Name	230472911
Secondary Th1 act	3.4	HUVEC IL-1beta	13.0
Secondary Th2 act	3.3	HUVEC IFN gamma	9.0
Secondary Tr1 act	1.2	HUVEC TNF alpha + IFN gamma	7.4
Secondary Th1 rest	0.4	HUVEC TNF alpha + IL4	2.1
Secondary Th2 rest	0.0	HUVEC IL-11	3.6
Secondary Tr1 rest	0.0	Lung Microvascular EC none	27.7
Primary Th1 act	0.0	Lung Microvascular EC TNF alpha + IL-1beta	8.2
Primary Th2 act	1.1	Microvascular Dermal EC none	4.2
Primary Tr1 act	1.4	Microsvasular Dermal EC	3.0
		TNF alpha + IL-1beta
Primary Th1 rest	0.5	Bronchial epithelium TNF alpha + IL1beta	9.1
Primary Th2 rest	0.5	Small airway epithelium none	22.1
Primary Tr1 rest	0.9	Small airway epithelium TNF alpha + IL-1beta	33.9
CD45RA CD4 lymphocyte act	5.0	Coronery artery SMC rest	6.2
CD45RO CD4 lymphocyte act	1.6	Coronery artery SMC TNF alpha + IL-1beta	11.3
CD8 lymphocyte act	0.4	Astrocytes rest	2.3
Secondary CD8 lymphocyte rest	1.3	Astrocytes TNF alpha + IL-1beta	3.1
Secondary CD8 lymphocyte act	0.0	KU-812 (Basophil) rest	1.9
CD4 lymphocyte none	0.0	KU-812 (Basophil)	10.9
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	0.0	CCD1106 (Keratinocytes) none	5.8
CH11
LAK cells rest	18.6	CCD1106 (Keratinocytes)	4.8
		TNF alpha + IL-1beta
LAK cells IL-2	0.6	Liver cirrhosis	1.9
LAK cells IL-2 + IL-12	0.0	NCI-H292 none	7.1
LAK cells IL-2 + IFN gamma	0.7	NCI-H292 IL-4	8.4
LAK cells IL-2 + IL-18	0.9	NCI-H292 IL-9	7.0
LAK cells PMA/ionomycin	62.4	NCI-H292 IL-13	5.6
NK Cells IL-2 rest	1.0	NCI-H292 IFN gamma	3.6
Two Way MLR 3 day	9.4	HPAEC none	9.1
Two Way MLR 5 day	3.9	HPAEC TNF alpha + IL-1beta	28.3
Two Way MLR 7 day	2.3	Lung fibroblast none	9.3
PBMC rest	0.6	Lung fibroblast TNF alpha + IL-	12.2
		1beta
PBMC PWM	1.1	Lung fibroblast IL-4	3.9
PBMC PHA-L	2.2	Lung fibroblast IL-9	11.8
Ramos (B cell) none	0.0	Lung fibroblast IL-13	5.4
Ramos (B cell) ionomycin	0.0	Lung fibroblast IFN gamma	19.5
B lymphocytes PWM	0.0	Dermal fibroblast CCD1070 rest	32.1
B lymphocytes CD40L and IL-4	1.4	Dermal fibroblast CCD1070 TNF	66.0
		alpha
EOL-1 dbcAMP	1.4	Dermal fibroblast CCD1070 IL-	21.8
		1beta
EOL-1 dbcAMP	1.4	Dermal fibroblast IFN gamma	42.3
PMA/ionomycin
Dendritic cells none	100.0	Dermal fibroblast IL-4	45.1
Dendritic cells LPS	34.9	Dermal Fibroblasts rest	15.7
Dendritic cells anti-CD40	44.8	Neutrophils TNFa + LPS	0.0
Monocytes rest	1.4	Neutrophils rest	0.6
Monocytes LPS	19.9	Colon	0.0
Macrophages rest	12.5	Lung	1.4
Macrophages LPS	11.2	Thymus	0.0
HUVEC none	5.9	Kidney	12.8
HUVEC starved	11.7

[1091]

TABLE ANJ
Panel 4D
	Rel.		Rel.
	Exp. ( )		Exp. (%)
	Ag2052,		Ag2052,
	Run		Run
Tissue Name	161706487	Tissue Name	161706487
Secondary Th1 act	2.6	HUVEC IL-1beta	2.1
Secondary Th2 act	1.7	HUVEC IFN gamma	5.2
Secondary Tr1 act	1.9	HUVEC TNF alpha + IFN gamma	5.7
Secondary Th1 rest	0.3	HUVEC TNF alpha + IL4	4.5
Secondary Th2 rest	0.5	HUVEC IL-11	2.6
Secondary Tr1 rest	0.6	Lung Microvascular EC none	9.9
Primary Th1 act	1.4	Lung Microvascular EC TNF alpha + IL-1beta	10.0
Primary Th2 act	0.7	Microvascular Dermal EC none	16.6
Primary Tr1 act	1.2	Microsvasular Dermal EC	9.2
		TNF alpha + IL-1beta
Primary Th1 rest	2.2	Bronchial epithelium TNF alpha + IL1beta	3.1
Primary Th2 rest	1.4	Small airway epithelium none	12.5
Primary Tr1 rest	0.2	Small airway epithelium TNF alpha + IL-1beta	46.0
CD45RA CD4 lymphocyte act	4.2	Coronery artery SMC rest	5.4
CD45RO CD4 lymphocyte act	1.4	Coronery artery SMC TNF alpha + IL-1beta	4.3
CD8 lymphocyte act	0.3	Astrocytes rest	2.2
Secondary CD8 lymphocyte rest	1.4	Astrocytes TNF alpha + IL-1beta	2.0
Secondary CD8 lymphocyte act	0.4	KU-812 (Basophil) rest	1.5
CD4 lymphocyte none	0.4	KU-812 (Basophil)	11.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	0.8	CCD1106 (Keratinocytes) none	3.1
CH11
LAK cells rest	43.2	CCD1106 (Keratinocytes)	0.8
		TNF alpha + IL-1beta
LAK cells IL-2	0.8	Liver cirrhosis	1.5
LAK cells IL-2 + IL-12	1.8	Lupus kidney	0.7
LAK cells IL-2 + IFN gamma	3.2	NCI-H292 none	5.8
LAK cells IL-2 + IL-18	2.1	NCI-H292 IL-4	5.5
LAK cells PMA/ionomycin	26.2	NCI-H292 IL-9	7.4
NK Cells IL-2 rest	0.3	NCI-H292 IL-13	2.7
Two Way MLR 3 day	9.2	NCI-H292 IFN gamma	3.3
Two Way MLR 5 day	9.3	HPAEC none	5.6
Two Way MLR 7 day	2.0	HPAEC TNF alpha + IL-1beta	10.7
PBMC rest	1.0	Lung fibroblast none	6.3
PBMC PWM	5.3	Lung fibroblast TNF alpha + IL-	6.3
		1beta
PBMC PHA-L	5.0	Lung fibroblast IL-4	10.4
Ramos (B cell) none	0.0	Lung fibroblast IL-9	8.1
Ramos (B cell) ionomycin	0.0	Lung fibroblast IL-13	5.6
B lymphocytes PWM	2.2	Lung fibroblast IFN gamma	15.4
B lymphocytes CD40L and IL-4	1.2	Dermal fibroblast CCD1070 rest	15.5
EOL-1 dbcAMP	0.7	Dermal fibroblast CCD1070 TNF	18.9
		alpha
EOL-1 dbcAMP	1.5	Dermal fibroblast CCD1070 IL-	11.1
PMA/ionomycin		1beta
Dendritic cells none	66.9	Dermal fibroblast IFN gamma	19.6
Dendritic cells LPS	37.6	Dermal fibroblast IL-4	21.2
Dendritic cells anti-CD40	77.9	IBD Colitis 2	0.2
Monocytes rest	5.1	IBD Crohn's	0.5
Monocytes LPS	17.2	Colon	3.9
Macrophages rest	100.0	Lung	19.8
Macrophages LPS	40.9	Thymus	12.9
HUVEC none	5.3	Kidney	2.4
HUVEC starved	10.6

[1092]

TABLE ANK
Panel 5 Islet
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag2052,		Ag2052,
	un		Run
Tissue Name	279370795	Tissue Name	279370795
97457_Patient-02go_adipose	15.6	94709_Donor 2 AM - A_adipose	24.7
97476_Patient-07sk_skeletal	0.0	94710_Donor 2 AM - B_adipose	24.7
muscle
97477_Patient-07ut_uterus	22.1	94711_Donor 2 AM - C_adipose	14.7
97478_Patient-07pl_placenta	13.1	94712_Donor 2 AD - A_adipose	64.2
99167_Bayer Patient 1	17.6	94713_Donor 2 AD - B_adipose	89.5
97482_Patient-08ut_uterus	15.3	94714_Donor 2 AD - C_adipose	66.4
97483_Patient-08pl_placenta	11.6	94742_Donor 3 U - A_Mesenchymal	17.3
		Stem Cells
97486_Patient-09sk_skeletal	4.8	94743_Donor 3 U - B_Mesenchymal	23.2
muscle		Stem Cells
97487_Patient-09ut_uterus	15.5	94730_Donor 3 AM - A_adipose	54.0
97488_Patient-09pl_placenta	7.9	94731_Donor 3 AM - B_adipose	76.3
97492_Patient-10ut_uterus	14.5	94732_Donor 3 AM - C_adipose	59.9
97493_Patient-10pl_placenta	23.8	94733_Donor 3 AD - A_adipose	100.0
97495_Patient-11go_adipose	11.9	94734_Donor 3 AD - B_adipose	92.0
97496_Patient-11sk_skeletal	3.2	94735_Donor 3 AD - C_adipose	32.1
muscle
97497_Patient-11ut_uterus	36.9	77138_Liver_HepG2untreated	62.9
97498_Patient-11pl_placenta	7.0	73556_Heart_Cardiac stromal cells	0.3
		(primary)
97500_Patient-12go_adipose	17.2	81735_Small Intestine	10.9
97501_Patient-12sk_skeletal	8.4	72409_Kidney_Proximal Convoluted	23.7
muscle		Tubule
97502_Patient-12ut_uterus	25.2	82685_Small intestine_Duodenum	9.3
97503_Patient-12pl_placenta	23.8	90650_Adrenal_Adrenocortical	8.4
		adenoma
94721_Donor 2 U -	61.6	72410_Kidney_HRCE	40.1
A_Mesenchymal Stem Cells
94722_Donor 2 U -	45.1	72411_Kidney_HRE	13.5
B_Mesenchymal Stem Cells
94723_Donor 2 U -	53.2	73139_Uterus_Uterine smooth	61.1
C_Mesenchymal Stem Cells		muscle cells

[1093] AI_comprehensive panel_v1.0 Summary: Ag2052 Highest expression of this gene is detected in synovium from an orthoarthritis (OA) patient (CT=20.3). High levels of expression of this gene are detected in samples derived from normal and orthoarthitis/rheumatoid arthritis bone and adjacent bone, cartilage, synovium and synovial fluid samples, from normal lung, COPD lung, emphysema, atopic asthma, asthma, allergy, 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.

[1094] CNS_neurodegeneration_v1.0 Summary: Ag5277/Ag5278 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[1095] General_screen_panel_v1.5 Summary: Ag5278 Highest expression of this gene is detected in breast cancer BT-549 cell line (CT=29). 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, melanoma and brain cancers. In addition, moderate to low levels of expression of this gene is also seen in all the regions of brain, in tissues with metabolic/endocrine functions such as pancreas, adrenal gland, thyroid, fetal liver and colon. Please see panel 1.3D for further discussion of this gene.

[1096] Ag5277 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[1097] HASS Panel v1.0 Summary: Ag2052 Two experiments with same probe and primer sets are in excellent agreement. This gene shows wide spread expression in this panel, with highest expression in primary renal proximal tubular epithelial cells cultured in vitro (CTs=20-22). The expression of this gene is also higher in the glioblastoma type of brain cancer compared to the medulloblastoma suggesting that it may play a role in glioblastoma development than medulloblastomas. Expression is also induced in the U87-MG(cells when they are deprived of nutrients, oxygen and exposed to an acidic pH than in the control population (comparing the control U87-MG F4 with U87-MG F5, F7, F10). This suggests that the serum-starved, hypoxic and acidotic regions of brain cancers may express this gene at a higher level and that this may be used as a marker for these regions.

[1098] Panel 1.3D Summary: Ag2052 This gene shows a widespread expression in this panel. Highest expression of this gene is detected in breast cancer BT-549 cell line (CT=24.9). 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, 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, melanoma and brain cancers.

[1099] Among tissues with metabolic or endocrine function, this gene is expressed at high levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[1100] 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.

[1101] Panel 2.2 Summary: Ag2052 Highest expression of this gene is detected in thyroid cancer (CT=23.9). High to moderate levels of expression of this gene is also seen in normal and cancer samples derived from melanoma, colon, gastric, bladder, liver, breast, thyroid, uterine, kidney, lung, ovarian and prostate cancers. Interestingly, higher levels of expression of this gene is associated with kidney and thyroid cancers as compared to corresponding normal tissue. Therefore, expression of this gene may bay used as diagnostic marker to detect the presence of these cancers. Furthermore, therapeutic modulation of this gene may be useful in the treatment of melanoma, colon, gastric, bladder, liver, breast, thyroid, uterine, kidney, lung, ovarian and prostate cancers.

[1102] Panel 4.1D Summary: Ag5278 Highest levels of expression of this gene is detected in resting dendritic cells (CT=32). Moderate to low levels of expression of this gene is also seen in activated dendrict cells, PMA/ionomycin stimulated LAK cells, LPS activated macrophage, lung rmicrovascular endothelial cells, activated HPAEC cells, small airway epithelium, and dermal fibroblasts. Therefore, therapeutic modulation of this gene or its protein product may alter the functions associated with these cell types and would be beneficial in the treatment of autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.

[1103] Ag5277 Expression of this gene is low/undetectable (CTs>35) across all of the samples on this panel.

[1104] Panel 4D Summary: Ag2052 Highest expression of this gene is detected in resting macrophage (CT=21). 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, dendritic cells, 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_screen_panel_v1.3 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.

[1105] Panel 5 Islet Summary: Ag2052 Highest expression of this gene is detected in a differentiated adipose tissue (CT=24.4). Moderate to high levels of expression is seen in placenta, uterus, adipose, skeletal muscle, small intestine, heart and kidney. This gene shows a ubiquitous expression which correlates to the expression in panel 1.3D. Please see panel 1.3D for further discussion of this gene.

[1106] AO. CG56836-04: Cathepsin B.

[1107] Expression of gene CG56836-04 was assessed using the primer-probe set Ag5264, described in Table AOA. Results of the RTQ-PCR runs are shown in Tables AOB, AOC and AOD.

TABLE AOA
Probe Name Ag5264
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-tcctgctgggtttctggt-3′	18	455	411
Probe	TET-5′-ccgtactccatccctccctgtgagc-3′-TAMRA	25	503	412
Reverse	5′-tgtttgtaggtogggctgta-3′	20	605	413

[1108]

TABLE AOB
CNS_neurodegeneration_v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag5264,		Ag5264,
	Run		Run
Tissue Name	230512807	issue Name	230512807
AD 1 Hippo	10.2	Control (Path) 3 Temporal Ctx	3.6
AD 2 Hippo	32.5	Control (Path) 4 Temporal Ctx	18.4
AD 3 Hippo	9.3	AD 1 Occipital Ctx	14.7
AD 4 Hippo	3.8	AD 2 Occipital Ctx (Missing)	0.0
AD 5 hippo	94.0	AD 3 Occipital Ctx	7.3
AD 6 Hippo	66.9	AD 4 Occipital Ctx	13.4
Control 2 Hippo	25.0	AD 5 Occipital Ctx	15.3
Control 4 Hippo	13.0	AD 6 Occipital Ctx	39.0
Control (Path) 3 Hippo	4.0	Control 1 Occipital Ctx	5.9
AD 1 Temporal Ctx	9.8	Control 2 Occipital Ctx	53.6
AD 2 Temporal Ctx	25.2	Control 3 Occipital Ctx	8.4
AD 3 Temporal Ctx	3.9	Control 4 Occipital Ctx	6.3
AD 4 Temporal Ctx	7.5	Control (Path) 1 Occipital Ctx	83.5
AD 5 Inf Temporal Ctx	74.7	Control (Path) 2 Occipital Ctx	6.0
AD 5 SupTemporal Ctx	43.8	Control (Path) 3 Occipital Ctx	1.7
AD 6 Inf Temporal Ctx	71.2	Control (Path) 4 Occipital Ctx	13.1
AD 6 Sup Temporal Ctx	41.8	Control 1 Parietal Ctx	2.9
Control 1 Temporal Ctx	5.9	Control 2 Parietal Ctx	30.1
Control 2 Temporal Ctx	45.1	Control 3 Parietal Ctx	12.3
Control 3 Temporal Ctx	12.0	Control (Path) 1 Parietal Ctx	100.0
Control 4 Temporal Ctx	6.7	Control (Path) 2 Parietal Ctx	12.6
Control (Path) 1 Temporal Ctx	47.3	Control (Path) 3 Parietal Ctx	2.5
Control (Path) 2 Temporal Ctx	15.9	Control (Path) 4 Parietal Ctx	44.1

[1109]

TABLE AOC
General_screening_panel_v1.5
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag5264,		Ag5264,
	Run		Run
Tissue Name	232936651	issue Name	232936651
Adipose	0.7	Renal ca. TK-10	3.6
Melanoma* Hs688(A).T	19.5	Bladder	3.8
Melanoma* Hs688(B).T	9.0	Gastric ca. (liver met.) NCI-N87	10.2
Melanoma* M14	24.7	Gastric ca. KATO III	5.5
Melanoma* LOXIMVI	15.6	Colon ca. SW-948	1.2
Melanoma* SK-MEL-5	9.7	Colon ca. SW480	7.0
Squamous cell carcinoma SCC-4	3.1	Colon ca.* (SW480 met) SW620	2.0
Testis Pool	0.4	Colon ca. HT29	0.6
Prostate ca.* (bone met) PC-3	2.0	Colon ca. HCT-116	3.1
Prostate Pool	0.6	Colon ca. CaCo-2	5.2
Placenta	3.7	Colon cancer tissue	8.6
Uterus Pool	0.2	Colon ca. SW1116	2.4
Ovarian ca. OVCAR-3	6.7	Colon ca. Colo-205	4.1
Ovarian ca. SK-OV-3	7.2	Colon ca. SW-48	1.3
Ovarian ca. OVCAR-4	4.2	Colon Pool	1.2
Ovarian ca. OVCAR-5	6.2	Small Intestine Pool	0.7
Ovarian ca. IGROV-1	1.5	Stomach Pool	1.3
Ovarian ca. OVCAR-8	2.2	Bone Marrow Pool	0.7
Ovary	1.4	Fetal Heart	0.5
Breast ca. MCF-7	2.7	Heart Pool	1.3
Breast ca. MDA-MB-231	4.9	Lymph Node Pool	2.2
Breast ca. BT 549	100.0	Fetal Skeletal Muscle	0.3
Breast ca. T47D	1.3	Skeletal Muscle Pool	1.3
Breast ca. MDA-N	1.1	Spleen Pool	1.2
Breast Pool	1.7	Thymus Pool	0.9
Trachea	3.0	CNS cancer (glio/astro) U87-MG	12.6
Lung	0.2	CNS cancer (glio/astro) U-118-MG	9.0
Fetal Lung	1.6	CNS cancer (neuro; met) SK-N-AS	2.1
Lung ca. NCI-N417	0.2	CNS cancer (astro) SF-539	7.4
Lung ca. LX-1	4.5	CNS cancer (astro) SNB-75	22.5
Lung ca. NCI-H146	0.2	CNS cancer (glio) SNB-19	1.7
Lung ca. SHP-77	1.6	CNS cancer (glio) SF-295	15.6
Lung ca. A549	4.1	Brain (Amygdala) Pool	1.4
Lung ca. NCI-H526	0.2	Brain (cerebellum)	5.6
Lung ca. NCI-H23	2.2	Brain (fetal)	1.0
Lung ca. NCI-H460	1.2	Brain (Hippocampus) Pool	1.3
Lung ca. HOP-62	5.6	Cerebral Cortex Pool	1.6
Lung ca. NCI-H522	1.4	Brain (Substantia nigra) Pool	1.5
Liver	1.7	Brain (Thalamus) Pool	2.1
Fetal Liver	4.9	Brain (whole)	3.1
Liver ca. HepG2	4..9	Spinal Cord Pool	1.6
Kidney Pool	2.4	Adrenal Gland	2.1
Fetal Kidney	1.0	Pituitary gland Pool	0.4
Renal ca. 786-0	1.0	Salivary Gland	1.6
Renal ca. A498	1.7	Thyroid (female)	16.7
Renal ca. ACHN	4.0	Pancreatic ca. CAPAN2	5.6
Renal ca. UO-31	11.2	Pancreas Pool	2.8

[1110]

TABLE AOD
Panel 4.1D
	Rel.		Rel.
	Exp. (%		Exp. (%)
	Ag5264,		Ag5264,
	Run		Run
Tissue Name	230472870	Tissue Name	230472870
Secondary Th1 act	4.0	HUVEC IL-1beta	9.2
Secondary Th2 act	3.3	HUVEC IFN gamma	7.2
Secondary Tr1 act	1.2	HUVEC TNF alpha + IFN gamma	4.6
Secondary Th1 rest	0.3	HUVEC TNF alpha + IL4	5.1
Secondary Th2 rest	0.2	HUVEC IL-11	4.5
Secondary Tr1 rest	0.2	Lung Microvascular EC none	32.5
Primary Th1 act	0.5	Lung Microvascular EC TNF alpha + IL-1beta	10.3
Primary Th2 act	0.7	Microvascular Dermal EC none	4.2
Primary Tr1 act	1.0	Microsvasular Dermal EC	2.8
		TNF alpha + IL-1beta
Primary Th1 rest	0.2	Bronchial epithelium TNF alpha + IL1beta	11.5
Primary Th2 rest	0.3	Small airway epithelium none	15.8
Primary Tr1 rest	0.2	Small airway epithelium TNF alpha + IL-1beta	20.2
CD45RA CD4 lymphocyte act	4.6	Coronery artery SMC rest	6.0
CD45RO CD4 lymphocyte act	1.7	Coronery artery SMC TNF alpha + IL-1beta	5.1
CD8 lymphocyte act	0.3	Astrocytes rest	1.5
Secondary CD8 lymphocyte rest	1.1	Astrocytes TNF alpha + IL-1beta	1.9
Secondary CD8 lymphocyte act	0.3	KU-812 (Basophil) rest	1.7
CD4 lymphocyte none	0.1	KU-812 (Basophil)	8.9
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	0.8	CCD1106 (Keratinocytes) none	6.8
CH11
LAK cells rest	39.2	CCD1106 (Keratinocytes)	5.0
		TNF alpha + IL-1beta
LAK cells IL-2	0.6	Liver cirrhosis	3.8
LAK cells IL-2 + IL-12	0.1	NCI-H292 none	3.6
LAK cells IL-2 + IFN gamma	0.3	NCI-H292 IL-4	4.7
LAK cells IL-2 + IL-18	0.3	NCI-H292 IL-9	5.4
LAK cells PMA/ionomycin	54.3	NCI-H292 IL-13	3.3
NK Cells IL-2 rest	0.6	NCI-H292 IFN gamma	2.4
Two Way MLR 3 day	9.0	HPAEC none	3.7
Two Way MLR 5 day	3.4	HPAEC TNF alpha + IL-1beta	27.0
Two Way MLR 7 day	1.3	Lung fibroblast none	10.7
PBMC rest	0.4	Lung fibroblast TNF alpha + IL-	10.4
		1beta
PBMC PWM	0.7	Lung fibroblast IL-4	4.5
PBMC PHA-L	2.7	Lung fibroblast IL-9	8.2
Ramos (B cell) none	0.0	Lung fibroblast IL-13	2.2
Ramos (B cell) ionomycin	0.0	Lung fibroblast IFN gamma	16.0
B lymphocytes PWM	0.5	Dermal fibroblast CCD1070 rest	17.6
B lymphocytes CD40L and IL-4	1.3	Dermal fibroblast CCD1070 TNF	16.6
		alpha
EOL-1 dbcAMP	1.0	Dermal fibroblast CCD1070 IL-	16.7
		1beta
EOL-1 dbcAMP	0.9	Dermal fibroblast IFN gamma	31.6
PMA/ionomycin
Dendritic cells none	100.0	Dermal fibroblast IL-4	20.3
Dendritic cells LPS	31.9	Dermal fibroblast rest	14.6
Dendritic cells anti-CD40	36.3	Neutrophils TNFa + LPS	0.2
Monocytes rest	1.4	Neutrophils rest	0.2
Monocytes LPS	40.9	Colon	0.0
Macrophages rest	26.1	Lung	1.4
Macrophages LPS	16.7	Thymus	0.2
HUVEC none	4.7	Kidney	9.7
HUVEC starved	5.8

[1111] CNS_neurodegeneration_v1.0 Summary: Ag5264 This panel confirms the expression of this gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.5 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.

[1112] General_screen_panel_v1.5 Summary: Ag5264 Highest expression of this gene is detected in breast cancer BT-549 cell line (CT=25). 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, 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, melanoma and brain cancers.

[1113] 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.

[1114] 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.

[1115] Panel 4.1D Summary: Ag5264 Highest levels of expression of this gene is detected in resting dendritic cells (CT=28.7). Moderate to low levels of expression of this gene is also seen in activated dendritic cells, resting and PMA/ionomycin stimulated LAK cells, monocytes, macrophage, different types of endothelial cells, small airway epithelium, lung and dermal fibroblasts and normal tissue represent by lung and kidney. This gene is upregulated in LPS treated monocytes, cytokine treated UPAEC, and activated secondary Th1, Th2 cells. Therefore, therapeutic modulation of this gene or its protein product may alter the functions associated with these cell types and would be beneficial in the treatment of autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.

[1116] AP. CG57284-03: RAS-Related Protein RAB-5C.

[1117] Expression of gene CG57284-03 was assessed using the primer-probe set Ag6892, described in Table APA. Results of the RTQ-PCR runs are shown in Tables APB and APC. Please note that this sequence represents a full-length physical clone.

TABLE APA
Probe Name Ag6892
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-gtgtcatccaggcagacagtct-3′	22	473	414
Probe	TET-5′-ccgctccaattgtgctctcctggtact-3′-TAMRA	27	507	415
Reverse	5′-cgctttqtcaagggacagttt-3′	21	538	416

[1118]

TABLE APB
General_screening_panel_v1.6
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag6892,		Ag6892,
	Run		Run
Tissue Name	278388295	issue Name	278388295
Adipose	11.0	Renal ca. TK-10	41.5
Melanoma* Hs688(A).T	37.4	Bladder	19.1
Melanoma* Hs688(B).T	33.0	Gastric ca. (liver met.) NCI-N87	26.4
Melanoma* M14	85.3	Gastric ca. KATO III	93.3
Melanoma* LOXIMVI	48.6	Colon ca. SW-948	15.7
Melanoma* SK-MEL-5	49.7	Colon ca. SW480	62.4
Squamous cell carcinoma SCC-4	28.5	Colon ca.* (SW480 met) SW620	9.5
Testis Pool	10.1	Colon ca. HT29	20.7
Prostate ca.* (bone met) PC-3	0.0	Colon ca. HCT-116	48.0
Prostate Pool	10.6	Colon ca. CaCo-2	49.7
Placenta	22.4	Colon cancer tissue	19.3
Uterus Pool	4.8	Colon ca. SW1116	6.7
Ovarian ca. OVCAR-3	18.9	Colon ca. Colo-205	13.3
Ovarian ca. SK-OV-3	63.3	Colon ca. SW-48	16.5
Ovarian ca. OVCAR-4	17.4	Colon Pool	15.5
Ovarian ca. OVCAR-5	41.5	Small Intestine Pool	8.7
Ovarian ca. IGROV-1	18.4	Stomach Pool	8.0
Ovarian ca. OVCAR-8	13.8	Bone Marrow Pool	8.5
Ovary	10.6	Fetal Heart	5.9
Breast ca. MCF-7	33.2	Heart Pool	6.3
Breast ca. MDA-MB-231	46.0	Lymph Node Pool	16.4
Breast ca. BT 549	37.4	Fetal Skeletal Muscle	5.4
Breast ca. T47D	35.1	Skeletal Muscle Pool	1.6
Breast ca. MDA-N	22.2	Spleen Pool	8.8
Breast Pool	12.7	Thymus pool	8.7
Trachea	12.0	CNS cancer (glio/astro) U87-MG	35.4
Lung	2.5	CNS cancer (glio/astro) U-118-MG	55.9
Fetal Lung	32.5	CNS cancer (neuro; met) SK-N-AS	52.1
Lung ca. NCI-N417	5.4	CNS cancer (astro) SF-539	28.9
Lung ca. LX-1	20.2	CNS cancer (astro) SNB-75	52.9
Lung ca. NCI-H146	8.6	CNS cancer (glio) SNB-19	21.2
Lung ca. SHP-77	20.2	CNS cancer (glio) SF-295	100.0
Lung ca. A549	51.1	Brain (Amygdala) Pool	10.6
Lung ca. NCI-H526	5.6	Brain (cerebellum)	49.0
Lung ca. NCI-H23	23.7	Brain (fetal)	25.9
Lung ca. NCI-H460	19.1	Brain (Hippocampus) Pool	13.0
Lung ca. HOP-62	21.0	Cerebral Cortex Pool	17.3
Lung ca. NCI-H522	31.4	Brain (Substantia nigra) Pool	11.2
Liver	5.7	Brain (Thalamus) Pool	19.6
Fetal Liver	19.8	Brain (whole)	23.0
Liver ca. HepG2	10.3	Spinal Cord Pool	12.5
Kidney Pool	15.9	Adrenal Gland	24.8
Fetal Kidney	14.0	Pituitary gland Pool	2.7
Renal ca. 786-0	24.3	Salivary Gland	11.3
Renal ca. A498	21.9	Thyroid (female)	9.8
Renal ca. ACHN	22.2	Pancreatic ca. CAPAN2	24.8
Renal ca. UO-31	35.4	Pancreas Pool	8.1

[1119]

TABLE APC
Panel 5 Islet
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag6892,		Ag6892,
	Run		Run
Tissue Name	305424859	Tissue Name	305424859
97457_Patient-02go_adipose	4.5	94709_Donor 2 AM - A_adipose	44.1
97476_Patient-07sk_skeletal	0.0	94710_Donor 2 AM - B_adipose	30.8
muscle
97477_Patient-07ut_uterus	8.2	94711_Donor 2 AM - C_adipose	21.0
97478_Patient-07pl_placenta	13.1	94712_Donor 2 AD - A_adipose	48.0
99167_Bayer Patient 1	23.2	94713_Donor 2 AD - B_adipose	54.0
97482_Patient-08ut_uterus	7.7	94714_Donor 2 AD - C_adipose	50.3
97483_Patient-08pl_placenta	18.9	94742_Donor 3 U - A_Mesenchymal	14.7
		Stem Cells
97486_Patient-09sk_skeletal	4.4	94743_Donor 3 U - B_Mesenchymal	10.4
muscle		Stem Cells
97487_Patient-09ut_uterus	19.6	94730_Donor 3 AM - A_adipose	53.2
97488_Patient-09pl_placenta	11.3	94731_Donor 3 AM - B_adipose	74.2
97492_Patient-10ut_uterus	12.2	94732_Donor 3 AM - C_adipose	58.6
97493_Patient-10pl_placenta	34.9	94733_Donor 3 AD - A_adipose	64.6
97495_Patient-11go_adipose	9.2	94734_Donor 3 AD - B_adipose	100.0
97496_Patient-11sk_skeletal	3.8	94735_Donor 3 AD - C_adipose	20.4
muscle
97497_Patient-11ut_uterus	25.0	77138_Liver_HepG2untreated	71.2
97498_Patient-11pl_placenta	8.8	73556_Heart_Cardiac stromal cells	18.6
		(primary)
97500_Patient-12go_adipose	10.4	81735_Small Intestine	12.4
97501_Patient-12sk_skeletal muscle	12.7	72409_Kidney_Proximal Convoluted	81.2
muscle		Tubule
97502_Patient-12ut_uterus	18.9	82685_Small intestine_Duodenum	8.1
97503_Patient-12pl_placenta	17.8	90650_Adrenal_Adrenocortical	4.8
		adenoma
94721_Donor 2 U -	27.9	72410_Kidney_HRCE	37.9
A_Mesenchymal Stem Cells
94722_Donor 2 U -	25.7	72411_Kidney_HRE	18.8
B_Mesenchymal Stem Cells
94723_Donor 2 U -	30.4	73139_Uterus_Uterine smooth	48.0
C_Mesenchymal Stem Cells		muscle cells

[1120] General_screen_panel_v1.6 Summary: Ag6892 Highest expression of this gene is seen in a brain cancer cell line (CT=24.1). This gene is ubiquitously expressed in this panel, with high levels of expression seen in brain, colon, gastric, lung, breast, ovarian, and melanoma cancer cell lines. This expression profile suggests a role for this gene product in cell survival and proliferation. Modulation of this gene product may be useful in the treatment of cancer.

[1121] 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.

[1122] 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.

[1123] In addition, this gene is expressed at much higher levels in fetal lung tissue (CT=25.7) when compared to expression in the adult counterpart (CT=29.4). Thus, expression of this gene may be used to differentiate between the fetal and adult source of this tissue.

[1124] Panel 5 Islet Summary: Ag6892 Highest expression is seen in adipose (CT=26), with nearly ubiquitous expression seen across the samples on this panel. High to moderate levels of expression are seen in metabolic tissues, including skeletal muscle, adipose, and placenta, in agreement with Panel 1.6. Please see that panel for discussion of this gene in metabolic disease.

[1125] AQ. CG57308-02: Sulfonylurea Receptor 1 Splice Variant.

[1126] Expression of gene CG57308-02 was assessed using the primer-probe set Ag7558, described in Table AQA. Results of the RTQ-PCR runs are shown in Tables AQB and AQC.

TABLE AQA
Probe Name Ag7558
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-tcgaagggcacatcatca-3′	18	4319	417
Probe	TET-5′-tgcctctgtccctggctgaaattctc-3′-TAMRA	26	4348	418
Reverse	5′-tgaagatgctggtcttcctca-3′	21	4400	419

[1127]

TABLE AQB
CNS_neurodegeneration_v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag7558,		Ag7558,
	Run		Run
Tissue Name	308750599	issue Name	308750599
AD 1 Hippo	4.2	Control (Path) 3 Temporal Ctx	3.3
AD 2 Hippo	16.4	Control (Path) 4 Temporal Ctx	50.3
AD 3 Hippo	1.7	AD 1 Occipital Ctx	11.1
AD 4 Hippo	11.3	AD 2 Occipital Ctx (Missing)	0.0
AD 5 Hippo	76.3	AD 3 Occipital Ctx	2.3
AD 6 Hippo	38.7	AD 4 Occipital Ctx	19.8
Control 2 Hippo	17.8	AD 5 Occipital Ctx	45.4
Control 4 Hippo	3.9	AD 6 Occipital Ctx	21.2
Control (Path) 3 Hippo	1.0	Control 1 Occipital Ctx	0.9
AD 1 Temporal Ctx	7.6	Control 2 Occipital Ctx	82.4
AD 2 Temporal Ctx	24.5	Control 3 Occipital Ctx	13.4
AD 3 Temporal Ctx	4.0	Control 4 Occipital Ctx	0.0
AD 4 Temporal Ctx	32.3	Control (Path) 1 Occipital Ctx	100.0
AD 5 Inf Temporal Ctx	78.5	Control (Path) 2 Occipital Ctx	17.1
AD 5 Sup Temporal Ctx	25.3	Control (Path) 3 Occipital Ctx	0.0
AD 6 Inf Temporal Ctx	39.2	Control (Path) 4 Occipital Ctx	31.9
AD 6 Sup Temporal Ctx	71.7	Control 1 Parietal Ctx	1.8
Control 1 Temporal Ctx	4.3	Control 2 Parietal Ctx	36.9
Control 2 Temporal Ctx	33.2	Control 3 Parietal Ctx	21.5
Control 3 Temporal Ctx	13.8	Control (Path) 1 Parietal Ctx	87.1
Control 3 Temporal Ctx	2.5	Control (Path) 2 Parietal Ctx	41.5
Control (Path) 1 Temporal Ctx	55.9	Control (Path) 3 Parietal Ctx	3.7
Control (Path) 2 Temporal Ctx	65.1	Control (Path) 4 Parietal Ctx	79.0

[1128]

TABLE AQC
Panel 5 Islet
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag7558,		Ag7558,
	Run		Run
Tissue Name	312000203	Tissue Name	312000203
97457_Patient-02go_adipose	0.0	94709_Donor 2 AM - A_adipose	0.0
97476_Patient-07sk_skeletal	0.0	94710_Donor 2 AM - B_adipose	0.0
muscle
97477_Patient-07ut_uterus	0.0	94711_Donor 2 AM - C_adipose	0.0
97478_Patient-07pl_placenta	0.0	94712_Donor 2 AD - A_adipose	0.0
99167_Bayer Patient 1	100.0	94713_Donor 2 AD - B_adipose	0.0
97482_Patient-08ut_uterus	0.0	94714_Donor 2 AD - C_adipose	0.0
97483_Patient-08pl_placenta	0.0	94742_Donor 3 U - A_Mesenchymal	0.0
		Stem Cells
97486_Patient-09sk_skeletal	0.0	94743_Donor 3 U - B_Mesenchymal	0.0
muscle		Stem Cells
97487_Patient-09ut_uterus	0.0	94730_Donor 3 AM - A_adipose	0.0
97488_Patient-09pl_placenta	0.0	94731_Donor 3 AM - B_adipose	0.0
97492_Patient-10ut_uterus	0.0	94732_Donor 3 AM - C_adipose	0.0
97493_Patient-10pl_placenta	0.0	94733_Donor 3 AD - A_adipose	0.0
97495_Patient-11go_adipose	0.0	94734_Donor 3 AD - B_adipose	0.0
97496_Patient-11sk_skeletal	0.0	94735_Donor 3 AD - C_adipose	0.0
muscle
97497_Patient-11ut_uterus	0.0	77138_Liver_HepG2untreated	0.0
97498_Patient-11pl_placenta	0.0	73556_Heart_Cardiac stromal cells	0.0
		(primary)
97500_Patient-12go_adipose	0.0	81735_Small Intestine	0.0
97501_Patient-12sk_skeletal	0.0	72409_Kidney_Proximal Convoluted	0.0
muscle		Tubule
97502_Patient-12ut_uterus	0.0	82685_Small intestine_Duodenum	0.0
97503_Patient-12pl_placenta	0.0	90650_Adrenal_Adrenocortical	0.0
		adenoma
94721_Donor 2 U -	0.0	72410_Kidney_HRCE	0.0
A_Mesenchymal Stem Cells
94722_Donor 2 U -	0.0	72411_Kidney_HRE	0.0
B_Mesenchymal Stem Cells
94723_Donor 2 U -	0.0	73139_Uterus_Uterine smooth	0.0
C_Mesenchymal Stem Cells		muscle cells

[1129] CNS_neurodegeneration_v1.0 Summary: Ag7558 Highest expression of this gene is seen in the occipital cortex of a control patient (CT=33). This panel does not show differential expression of this gene in Alzheimer's disease. However, this profile does show the expression of this gene at low levels in the brain. 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.

[1130] Panel 4.1D Summary: Ag7558 Expression of this gene is low/undetectable in all samples on this panel (CTs>35).

[1131] Panel 5 Islet Summary: Ag7558 Expression of this gene is limited to pancreatic islet cells (CT=34.6). This gene codes for a variant of SURI. SURI is a subunit of the pancreatic beta cell K+ channel that regulates insulin release in glucose-stimulated cells. Thus, therapeutic modulation of SURI variant encoded by this gene may be used as a treatment for the enhancement of insulin secretion in Type 2 diabetes.

[1132] AR. CG93659-03: Mirogen-Activated Protein Kinase Kinase Kinase 9.

[1133] Expression of gene CG93659-03 was assessed using the primer-probe set Ag4828, described in Table ARA. Results of the RTQ-PCR runs are shown in Tables ARB and ARC.

TABLE ARA
Probe Name Ag4828
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-gaggaatctgagatgctcaaga-3′	22	1275	420
Probe	TET-5′-caacgctctctctacatcgacctcgg-3′-TAMRA	26	1299	421
Reverse	5′-tccccgaacaagattgaagt-3′	20	1339	422

[1134]

TABLE ARB
General_screening_panel_v1.4
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4828,		Ag4828,
	Run		Run
Tissue Name	217081802	issue Name	217081802
Adipose	53.6	Renal ca. TK-10	10.6
Melanoma* Hs688(A).T	15.5	Bladder	31.9
Melanoma* Hs688(B).T	17.4	Gastric ca. (liver met.) NCI-N87	36.3
Melanoma* M14	3.5	Gastric ca. KATO III	12.2
Melanoma* LOXIMVI	3.2	Colon ca. SW-948	5.4
Melanoma* SK-MEL-5	0.9	Colon ca. SW480	25.0
Squamous cell carcinoma SCC-4	7.0	Colon ca.* (SW480 met) SW620	2.5
Testis Pool	4.7	Colon ca. HT29	14.3
Prostate ca.* (bone met) PC-3	6.3	Colon ca. HCT-116	2.1
Prostate Pool	3.9	Colon ca. CaCo-2	15.9
Placenta	39.0	Colon cancer tissue	39.8
Uterus Pool	9.0	Colon ca. SW1116	3.4
Ovarian ca. OVCAR-3	15.7	Colon ca. Colo-205	8.8
Ovarian ca. SK-OV-3	46.3	Colon ca. SW-48	5.4
Ovarian ca. OVCAR-4	7.1	Colon Pool	16.2
Ovarian ca. OVCAR-5	30.6	Small Intestine Pool	9.3
Ovarian ca. IGROV-1	14.1	Stomach Pool	17.3
Ovarian ca. OVCAR-8	2.7	Bone Marrow Pool	7.0
Ovary	4.5	Fetal Heart	2.9
Breast ca. MCF-7	100.0	Heart Pool	7.9
Breast ca. MDA-MB-231	9.2	Lymph Node Pool	15.2
Breast ca. BT 549	73.2	Fetal Skeletal Muscle	1.7
Breast ca. T47D	66.0	Skeletal Muscle Pool	9.8
Breast ca. MDA-N	0.9	Spleen Pool	45.7
Breast Pool	24.1	Thymus Pool	15.9
Trachea	18.0	CNS cancer (glio/astro) U87-MG	7.6
Lung	6.7	CNS cancer (glio/astro) U-118-MG	7.9
Fetal Lung	68.3	CNS cancer (neuro; met) SK-N-AS	2.6
Lung ca. NCI-N417	0.2	CNS cancer (astro) SF-539	2.3
Lung ca. LX-1	11.8	CNS cancer (astro) SNB-75	14.1
Lung ca. NCI-H146	0.0	CNS cancer (glio) SNB-19	11.1
Lung ca. SHP-77	0.1	CNS cancer (glio) SF-295	31.9
Lung ca. A549	36.6	Brain (Amygdala) Pool	2.7
Lung ca. NCI-H526	0.0	Brain (cerebellum)	1.4
Lung ca. NCI-H23	13.4	Brain (fetal)	4.9
Lung ca. NCI-H460	17.6	Brain (Hippocampus) Pool	3.7
Lung ca. HOP-62	13.2	Cerebral Cortex Pool	3.5
Lung ca. NCI-H522	2.1	Brain (Substantia nigra) Pool	2.7
Liver	1.0	Brain (Thalamus) Pool	4.5
Fetal Liver	2.8	Brain (whole)	4.5
Liver ca. HepG2	8.1	Spinal Cord Pool	3.8
Kidney Pool	31.4	Adrenal Gland	9.5
Fetal Kidney	7.7	Pituitary gland Pool	1.4
Renal ca. 786-0	10.9	Salivary Gland	2.5
Renal ca. A498	5.2	Thyroid (female)	7.7
Renal ca. ACHN	2.5	Pancreatic ca. CAPAN2	34.4
Renal ca. UO-31	14.9	Pancreas Pool	19.6

[1135]

TABLE ARC
Panel 5D
	Rel.		Rel.
	Exp. %)		Exp. (%)
	Ag4828,		Ag4828,
	Run		Run
Tissue Name	219436967	Tissue Name	219436967
97457_Patient-02go_adipose	33.9	94709_Donor 2 AM - A_adipose	10.8
97476_Patient-07sk_skeletal	33.4	94710_Donor 2 AM - B_adipose	9.3
muscle
97477_Patient-07ut_uterus	59.5	94711_Donor 2 AM - C_adipose	3.0
97478_Patient-07pl_placenta	39.8	94712_Donor 2 AD - A_adipose	13.7
97481_Patient-08sk_skeletal	25.9	94713_Donor 2 AD - B_adipose	10.0
muscle
97482_Patient-08ut_uterus	19.8	94714_Donor 2 AD - C_adipose	6.7
97483_Patient-08pl_placenta	41.5	94742_Donor 3 U - A_Mesenchymal	4.7
		Stem Cells
97486_Patient-09sk_skeletal	6.5	94743_Donor 3 U - B_Mesenchymal	2.8
muscle		Stem Cells
97487_Patient-09ut_uterus	8.1	94730_Donor 3 AM - A_adipose	6.3
97488_Patient-09pl_placenta	38.4	94731_Donor 3 AM - B_adipose	2.4
97492_Patient-10ut_uterus	30.6	94732_Donor 3 AM - C_adipose	2.2
97493_Patient-10pl_placenta	72.7	94733_Donor 3 AD - A_adipose	10.2
97495_Patient-11go_adipose	100.0	94734_Donor 3 AD - B_adipose	5.5
97496_Patient-11sk_skeletal	5.8	94735_Donor 3 AD - C_adipose	4.7
muscle
97497_Patient-11ut_uterus	20.6	77138_Liver_HepG2untreated	14.4
97498_Patient-11pl_placenta	50.0	73556_Heart_Cardiac stromal cells	1.9
		(primary)
97500_Patient-12go_adipose	82.4	81735_Small Intestine	17.2
97501_Patient-12sk_skeletal	19.2	72409_Kidney_Proximal Convoluted	0.9
muscle		Tubule
97502_Patient-12ut_uterus	23.7	82685_Small intestine_Duodenum	19.1
97503_Patient-12pl_placenta	57.0	90650_Adrenal_Adrenocortical	8.8
		adenoma
94721_Donor 2 U -	1.6	72410_Kidney_HRCE	7.6
A_Mesenchymal Stem Cells
94722_Donor 2 U -	3.0	72411_Kidney_HRE	13.5
B_Mesenchymal Stem Cells
94723_Donor 2 U -	2.1	73139_Uterus_Uterine smooth	2.0
C_Mesenchymal Stem Cells		muscle cells

[1136] General_screen_panel_v1.4 Summary: Ag4828 Highest expression of this gene is detected in a breast cancer MCF-7 cell line(CT=27.6). Interestingly, this gene is expressed at much higher levels in fetal (CT=28) when compared to adult lung (CT=31).

[1137] This observation suggests that expression of this gene can be used to distinguish fetal from adult lung. In addition, the relative overexpression of this gene in fetal lung suggests that the protein product may enhance lung growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of lung related diseases.

[1138] In addition significant expression of this gene is found in a number of cancer (pancreatic, CNS, colon, lung, breast, ovary, prostate, melanoma) cell lines. Therefore, therapeutic modulation of the activity of this gene or its protein product, through the use of small molecule drugs, might be beneficial in the treatment of these cancers.

[1139] Among tissues with metabolic or endocrine function, this gene is expressed at high to moderate levels in pancreas, adipose, adrenal gland, thyroid, skeletal muscle, heart, fetal liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[1140] This gene encodes a protein that is homologous to mitogen-activated protein kinase kinase kinase 8 (MAP3K8)(COT proto-oncogene serine/threonine-protein kinase) (C-COT) (Cancer osaka thyroid oncogene). COT is able to enhance the TNF alpha production and to activate NF-kB. Both events are connected with insulin resistance and type II diabetes (1, 2, 3). Inhibition of COT kinase would prevent overproduction of TNF alpha and activation of NFkB, thus improving insulin resistance and diabetes.

[1141] 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. Recently, MKK6, a related protein, has been shown to associated with Alzheimer's disease (4). Therefore, based on the homology of this protein to MKK6 and the presence of this gene in the brain, we predict that this putative MAP3K8 may play a role in central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[1142] References:

[1143] 1. Ballester A, Velasco A, Tobena R, Alemany S. Cot kinase activates tumor necrosis factor-alpha gene expression in a cyclosporin A-resistant manner. J. Biol. Chem. 1998. 273, 14099-106. PMID: 9603908.

[1144] 2. Bierhaus A, Schiekofer S, Schwaninger M, Andrassy M, Humpert P M, Chen J, Hong M, Luther T, Henle T, Kloting I, Morcos M, Hofmann M, Tritschler H, Weigle B, Kasper M, Smith M, Perry G, Schmidt A M, Stern D M, Haring H U, Schleicher E, Nawroth P P. Diabetes-associated sustained activation of the transcription factor nuclear factor-kappaB. Diabetes, 2001 50, 2792-808. PMID: 11723063.

[1145] 3. Belich M P, Salmeron A, Johnston L H, Ley S C. TPL-2 kinase regulates the proteolysis of the NF-kappaB-inhibitory protein NF-kappaB1 p105. Nature. 1999 397, 363-8. PMID: 9950430.

[1146] 4. Zhu X, Rottkamp C A, Hartzler A, Sun Z, Takeda A, Boux H, Shimohama S, Perry G, Smith M A. (2001) Activation of MKK6, an upstream activator of p38, in Alzheimer's disease. J Neurochem 79(2):311-8

[1147] Panel 5D Summary: Ag4828 Highest expression of this gene is detected in adipose tissue (CT=29). Low to moderate expression of this gene is seen in wide range of samples used in this panel including adipose, skeletal muscle, uterus, and placenta. This wide spread expression of this gene in tissues with metabolic or endocrine function, suggests that this gene plays a role in endocrine/metabolically related diseases, such as obesity and diabetes.

[1148] This gene encodes a MAP3K8-like protein. Recently, activation of MAP kinase, ERK, a related protein, by modified LDL in vascular smooth muscle cells has been implicated in the development of atherosclerosis in diabetes (Ref. 1). Therefore, this putative MAP3K8 may also play a role in the development of this disease. Therefore, therapeutic modulation of the activity of this gene or its protein product, through the use of small molecule drugs, might be beneficial in the treatment of artheroscierosis and diabetes.

[1149] References:

[1150] 1. Velarde V, Jenkins A J, Christopher J, Lyons T J, Jaffa A A. (2001) Activation of MAPK by modified low-density lipoproteins in vascular smooth muscle cells. J Appl Physiol 91(3):1412-20

[1151] AS. CG94521-02 and CG94521-03: Cytoplasmic Glycerol-3-Phosphate Dehydrogenase [NAD+].

[1152] Expression of gene CG94521-02 and CG94521-03 was assessed using the primer-probe set Ag3924, described in Table ASA. Results of the RTQ-PCR runs are shown in Tables ASB, ASC, ASD, ASE and ASF. Please note that these sequences represent full-length physical clones.

TABLE ASA
Probe Name Ag3924
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-actgggaagaccattgaagagt-3′	22	197	423
Probe	TET-5′-aaaagctccaaggaccgcagacttct-3′-TAMRA	26	147	424
Reverse	5′-gtttgaggatgcggtacactt-3′	21	122	425

[1153]

TABLE ASB
CNS_neurodegeneration_v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag3924,		Ag3924,
	Run		Run
Tissue Name	212343350	issue Name	212343350
AD 1 Hippo	8.4	Control (Path) 3 Temporal Ctx	6.0
AD 2 Hippo	21.9	Control (Path) 4 Temporal Ctx	2.8
AD 3 Hippo	8.4	AD 1 Occipital Ctx	14.4
AD 4 Hippo	7.5	AD 2 Occipital Ctx (Missing)	0.0
AD 5 hippo	92.7	AD 3 Occipital Ctx	4.8
AD 6 Hippo	24.5	AD 4 Occipital Ctx	14.0
Control 2 Hippo	25.7	AD 5 Occipital Ctx	14.0
Control 4 Hippo	7.3	AD 6 Occipital Ctx	55.5
Control (Path) 3 Hippo	8.8	Control 1 Occipital Ctx	6.1
AD 1 Temporal Ctx	8.3	Control 2 Occipital Ctx	47.3
AD 2 Temporal Ctx	23.8	Control 3 Occipital Ctx	9.8
AD 3 Temporal Ctx	4.2	Control 4 Occipital Ctx	4.5
AD 4 Temporal Ctx	15.1	Control (Path) 1 Occipital Ctx	64.6
AD 5 Inf Temporal Ctx	100.0	Control (Path) 2 Occipital Ctx	8.6
AD 5 SupTemporal Ctx	32.3	Control (Path) 3 Occipital Ctx	3.9
AD 6 Inf Temporal Ctx	39.0	Control (Path) 4 Occipital Ctx	15.8
AD 6 Sup Temporal Ctx	33.2	Control 1 Parietal Ctx	5.0
Control 1 Temporal Ctx	4.5	Control 2 Parietal Ctx	40.3
Control 2 Temporal Ctx	44.4	Control 3 Parietal Ctx	14.6
Control 3 Temporal Ctx	11.1	Control (Path) 1 Parietal Ctx	70.7
Control 4 Temporal Ctx	4.4	Control (Path) 2 Parietal Ctx	15.5
Control (Path) 1 Temporal Ctx	49.0	Control (Path) 3 Parietal Ctx	4.9
Control (Path) 2 Temporal Ctx	29.9	Control (Path) 4 Parietal Ctx	39.5

[1154]

TABLE ASC
General_screening_panel_v1.4
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag3924,		Ag3924,
	Run		Run
Tissue Name	219515221	issue Name	219515221
Adipose	14.0	Renal ca. TK-10	7.1
Melanoma* Hs688(A).T	3.6	Bladder	8.1
Melanoma* Hs688(B).T	4.9	Gastric ca. (liver met.) NCI-N87	7.7
Melanoma* M14	15.1	Gastric ca. KATO III	17.4
Melanoma* LOXIMVI	6.2	Colon ca. SW-948	25.5
Melanoma* SK-MEL-5	37.6	Colon ca. SW480	28.3
Squamous cell carcinoma SCC-4	1.1	Colon ca.* (SW480 met) SW620	6.6
Testis Pool	6.3	Colon ca. HT29	4.1
Prostate ca.* (bone met) PC-3	47.0	Colon ca. HCT-116	25.0
Prostate Pool	18.6	Colon ca. CaCo-2	6.9
Placenta	6.3	Colon cancer tissue	7.6
Uterus Pool	5.1	Colon ca. SW1116	5.2
Ovarian ca. OVCAR-3	11.3	Colon ca. Colo-205	2.6
Ovarian ca. SK-OV-3	6.8	Colon ca. SW-48	4.4
Ovarian ca. OVCAR-4	12.2	Colon Pool	9.9
Ovarian ca. OVCAR-5	17.9	Small Intestine Pool	9.3
Ovarian ca. IGROV-1	8.2	Stomach Pool	5.2
Ovarian ca. OVCAR-8	3.5	Bone Marrow Pool	4.9
Ovary	9.6	Fetal Heart	26.1
Breast ca. MCF-7	100.0	Heart Pool	23.7
Breast ca. MDA-MB-231	11.4	Lymph Node Pool	8.7
Breast ca. BT 549	11.4	Fetal Skeletal Muscle	11.2
Breast ca. T47D	40.9	Skeletal Muscle Pool	62.0
Breast ca. MDA-N	11.7	Spleen Pool	9.7
Breast Pool	8.3	Thymus Pool	5.8
Trachea	15.4	CNS cancer (glio/astro) U87-MG	18.2
Lung	2.8	CNS cancer (glio/astro) U-118-MG	11.3
Fetal Lung	21.8	CNS cancer (neuro; met) SK-N-AS	6.6
Lung ca. NCI-N417	13.4	CNS cancer (astro) SF-539	4.0
Lung ca. LX-1	8.2	CNS cancer (astro) SNB-75	21.9
Lung ca. NCI-H146	4.5	CNS cancer (glio) SNB-19	7.6
Lung ca. SHP-77	13.3	CNS cancer (glio) SF-295	24.0
Lung ca. A549	16.6	Brain (Amygdala) Pool	11.4
Lung ca. NCI-H526	2.4	Brain (cerebellum)	10.2
Lung ca. NCI-H23	2.0	Brain (fetal)	27.2
Lung ca. NCI-H460	2.9	Brain (Hippocampus) Pool	11.6
Lung ca. HOP-62	6.6	Cerebral Cortex Pool	17.2
Lung ca. NCI-H522	14.3	Brain (Substantia nigra) Pool	10.4
Liver	0.3	Brain (Thalamus) Pool	18.9
Fetal Liver	1.1	Brain (whole)	17.7
Liver ca. HepG2	3.4	Spinal Cord Pool	14.3
Kidney Pool	26.4	Adrenal Gland	37.9
Fetal Kidney	6.7	Pituitary gland Pool	5.0
Renal ca. 786-0	3.0	Salivary Gland	11.1
Renal ca. A498	1.4	Thyroid (female)	17.0
Renal ca. ACHN	2.5	Pancreatic ca. CAPAN2	2.8
Renal ca. UO-31	10.1	Pancreas Pool	13.3

[1155]

TABLE ASD
Panel 4.1D
	Rel.		Rel.
	Exp. (%		Exp. (%)
	Ag3924,		Ag3924,
	Run		Run
Tissue Name	170552351	Tissue Name	170552351
Secondary Th1 act	33.9	HUVEC IL-1beta	19.6
Secondary Th2 act	35.4	HUVEC IFN gamma	32.3
Secondary Tr1 act	29.3	HUVEC TNF alpha + IFN gamma	8.6
Secondary Th1 rest	14.8	HUVEC TNF alpha + IL4	19.1
Secondary Th2 rest	23.7	HUVEC IL-11	17.2
Secondary Tr1 rest	15.8	Lung Microvascular EC none	16.8
Primary Th1 act	31.0	Lung Microvascular EC TNF alpha + IL-1beta	11.0
Primary Th2 act	33.7	Microvascular Dermal EC none	27.7
Primary Tr1 act	33.9	Microsvasular Dermal EC	8.6
		TNF alpha + IL-1beta
Primary Th1 rest	27.4	Bronchial epithelium TNF alpha + IL1beta	6.7
Primary Th2 rest	15.3	Small airway epithelium none	4.7
Primary Tr1 rest	34.2	Small airway epithelium TNF alpha + IL-1beta	4.0
CD45RA CD4 lymphocyte act	17.4	Coronery artery SMC rest	8.1
CD45RO CD4 lymphocyte act	28.3	Coronery artery SMC TNF alpha + IL-1beta	4.4
CD8 lymphocyte act	24.1	Astrocytes rest	16.4
Secondary CD8 lymphocyte rest	18.2	Astrocytes TNF alpha + IL-1beta	11.9
Secondary CD8 lymphocyte act	15.2	KU-812 (Basophil) rest	37.1
CD4 lymphocyte none	12.8	KU-812 (Basophil)	35.6
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	21.0	CCD1106 (Keratinocytes) none	9.5
CH11
LAK cells rest	17.8	CCD1106 (Keratinocytes)	4.8
		TNF alpha + IL-1beta
LAK cells IL-2	26.6	Liver cirrhosis	14.4
LAK cells IL-2 + IL-12	17.8	NCI-H292 none	42.9
LAK cells IL-2 + IFN gamma	17.8	NCI-H292 IL-4	57.0
LAK cells IL-2 + IL-18	32.5	NCI-H292 IL-9	81.2
LAK cells PMA/ionomycin	7.9	NCI-H292 IL-13	60.7
NK Cells IL-2 rest	35.6	NCI-H292 IFN gamma	39.0
Two Way MLR 3 day	17.3	HPAEC none	21.2
Two Way MLR 5 day	17.1	HPAEC TNF alpha + IL-1beta	13.4
Two Way MLR 7 day	100.0	Lung fibroblast none	18.0
PBMC rest	15.6	Lung fibroblast TNF alpha + IL-	6.0
		1beta
PBMC PWM	16.5	Lung fibroblast IL-4	19.5
PBMC PHA-L	13.8	Lung fibroblast IL-9	30.8
Ramos (B cell) none	64.6	Lung fibroblast IL-13	22.2
Ramos (B cell) ionomycin	70.2	Lung fibroblast IFN gamma	20.0
B lymphocytes PWM	23.8	Dermal fibroblast CCD1070 rest	12.5
B lymphocytes CD40L and IL-4	17.0	Dermal fibroblast CCD1070 TNF	30.1
		alpha
EOL-1 dbcAMP	10.8	Dermal fibroblast CCD1070 IL-	5.4
		1beta
EOL-1 dbcAMP	2.2	Dermal fibroblast IFN gamma	8.2
PMA/ionomycin
Dendritic cells none	13.6	Dermal fibroblast IL-4	17.8
Dendritic cells LPS	4.5	Dermal Fibroblast rest	20.0
Dendritic cells anti-CD40	21.6	Neutrophils TNFa + LPS	2.1
Monocytes rest	19.8	Neutrophils rest	3.6
Monocytes LPS	3.0	Colon	35.6
Macrophages rest	14.9	Lung	27.7
Macrophages LPS	1.7	Thymus	27.7
HUVEC none	16.7	Kidney	66.4
HUVEC starved	17.7

[1156]

TABLE ASE
Panel 5 Islet
	Rel.		Rel.
	Exp. (%		Exp. (%)
	Ag3924,		Ag3924,
	Run		Run
Tissue Name	268363571	Tissue Name	268363571
97457_Patient-02go_adipose	18.2	94709_Donor 2 AM - A_adipose	19.6
97476_Patient-07sk_skeletal	10.6	94710_Donor 2 AM - B_adipose	13.3
muscle
97477_Patient-07ut_uterus	10.2	94711_Donor 2 AM - C_adipose	11.0
97478_Patient-07pl_placenta	17.0	94712_Donor 2 AD - A_adipose	9.5
99167_Bayer Patient 1	6.5	94713_Donor 2 AD - B_adipose	21.9
97482_Patient-08ut_uterus	6.8	94714_Donor 2 AD - C_adipose	16.7
97483_Patient-08pl_placenta	11.7	94742_Donor 3 U - A_Mesenchymal	1.8
		Stem Cells
97486_Patient-09sk_skeletal	10.6	94743_Donor 3 U - B_Mesenchymal	1.7
muscle		Stem Cells
97487_Patient-09ut_uterus	12.0	94730_Donor 3 AM - A_adipose	19.6
97488_Patient-09pl_placenta	15.4	94731_Donor 3 AM - B_adipose	12.5
97492_Patient-10ut_uterus	12.9	94732_Donor 3 AM - C_adipose	12.2
97493_Patient-10pl_placenta	29.5	94733_Donor 3 AD - A_adipose	10.2
97495_Patient-11go_adipose	17.9	94734_Donor 3 AD - B_adipose	9.2
97496_Patient-11sk_skeletal	70.7	94735_Donor 3 AD - C_adipose	8.9
muscle
97497_Patient-11ut_uterus	18.8	77138_Liver_HepG2untreated	11.1
97498_Patient-11pl_placenta	10.3	73556_Heart_Cardiac stromal cells	5.2
		(primary)
97500_Patient-12go_adipose	31.9	81735_Small Intestine	15.9
97501_Patient-12sk_skeletal	100.0	72409_Kidney_Proximal Convoluted	6.5
muscle		Tubule
97502_Patient-12ut_uterus	23.8	82685_Small intestine_Duodenum	17.0
97503_Patient-12pl_placenta	8.7	90650_Adrenal_Adrenocortical	14.4
		adenoma
94721_Donor 2 U -	3.9	72410_Kidney_HRCE	11.5
A_Mesenchymal Stem Cells
94722_Donor 2 U -	2.8	72411_Kidney_HRE	3.4
B_Mesenchymal Stem Cells
94723_Donor 2 U -	4.8	73139_Uterus_Uterine smooth	2.1
C_Mesenchymal Stem Cells		muscle cells

[1157]

TABLE ASF
general oncology screening panel_v_2.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag3924,		Ag3924,
	Run		Run
Tissue Name	268143856	Tissue Nme	268143856
Colon cancer 1	60.3	Bladder NAT 2	3.3
Colon NAT 1	29.7	Bladder NAT 3	2.4
Colon cancer 2	26.1	Bladder NAT 4	25.7
Colon NAT 2	60.7	Prostate adenocarcinoma 1	100.0
Colon cancer 3	88.9	Prostate adenocarcinoma 2	14.6
Colon NAT 3	88.9	Prostate adenocarcinoma 3	86.5
Colon malignant cancer 4	98.6	Prostate adenocarcinoma 4	34.9
Colon NAT 4	29.5	Prostate NAT 5	26.2
Lung cancer 1	17.3	Prostate adenocarcinoma 6	24.5
Lung NAT 1	7.9	Prostate adenocarcinoma 7	39.5
Lung cancer 2	31.9	Prostate adenocarcinoma 8	15.2
Lung NAT 2	14.8	Prostate adenocarcinoma 9	53.6
Squamous cell carcinoma 3	34.2	Prostate NAT 10	12.6
Lung NAT 3	5.0	Kidney cancer 1	12.0
Metastatic melanoma 1	28.3	Kidney NAT 1	25.9
Melanoma 2	4.8	Kidney cancer 2	53.6
Melanoma 3	12.9	Kidney NAT 2	64.6
Metastatic melanoma 4	42.6	Kidney cancer 3	12.5
Metastatic melanoma 5	70.7	Kidney NAT 3	26.6
Bladder cancer 1	9.3	Kidney cancer 4	15.0
Bladder NAT 1	0.0	Kidney NAT 4	14.6
Bladder cancer 2	17.7

[1158] CNS_neurodegeneration_v1.0 Summary: Ag3924 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 1.4 for discussion of this gene in the central nervous system.

[1159] General_screen_panel_v1.4 Summary: Ag3924 Highest expression of this gene is seen in a breast cancer cell line (CT=25.3). This gene is ubiquitously 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.

[1160] Among tissues with metabolic function, this gene is expressed at moderate to high levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetalskeletal 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. This gene encodes a novel glycerol 3-phosphate dehydrogenase (G3PD).

[1161] Similar to known cytosolic glycerol 3-phosphate dehydrogenase, this putative G3PD may contribute to glycerol synthesis and link glycolysis with TG production. This gene is highly expressed in skeletal muscle and diabetic skeletal muscle on Panel 5I. Diabetic skeletal muscle has increased glycolytic activity and increased lipid content that interfere with insulin sensitivity. Inhibition of G3PD may balance disproportionate glycolysis and impair accumulation of TG in skeletal muscle. Thus, an antagonist of this novel G3PD may be beneficial for the treatment of diabetes.

[1162] 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.

[1163] In addition, this gene is expressed at much higher levels in fetal lung tissue (CT=27.5) when compared to expression in the adult counterpart (CT=30.5). Thus, expression of this gene may be used to differentiate between the fetal and adult source of this tissue.

[1164] Panel 4.1D Summary: Ag3924 Highest expression is seen in a sample derived from an MLR, where the sample was take 7 days after the reaction (CT=27.6). This gene is also expressed at high to moderate levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screen_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.

[1165] Panel 5 Islet Summary: Ag3924 Highest expression is seen in skeletal muscle from a diabetic patient (patient 12) (CT=28). This panel confirms expression of this gene in metabolic tissues including adipose, skeletal muscle and placenta. Please see Panel 1.4 for discussion of this gene in metabolic disease.

[1166] General oncology screening panel_v—2.4 Summary: Ag3924 Highest expression is seen in a prostate cancer sample (CT=28.2). Prominent expression is also seen in melanoma samples, as well as in normal and malignant kidney, colon and lung. Thus, modulation of this gene may be useful in the treatment of prostate cancer and melanoma.

[1167] AT. CG96613-02 and CG96613-03: Splice Variant of PDK1.

[1168] Expression of gene CG96613-02 and CG96613-03 was assessed using the primer-probe sets Ag1778 and Ag5110, described in Tables ATA and ATB. Results of the RTQ-PCR runs are shown in Tables ATC, ATD, ATE, ATF, ATG and ATH. Please note that probe-primer set Agl778 is specific for CG96613-03.

TABLE ATA
Probe Name Ag1778
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-gattgcccatatcacgtcttta-3′	22	1241	426
Probe	TET-5′-cgcacaatacttccaaggagacctga-3′-TAMRA	26	1263	427
Reverse	5′-gataactgcatctgtcccgtaa-3′	22	1308	428

[1169]

TABLE ATB
Probe Name Ag5110
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-tgtatggcctgcaagatgat-3′	20	559	429
Probe	TET-5′-tcattcccacaatggcccagg-3′-TAMRA	21	623	430
Reverse	5′-agctctccttgtattcaatcaca-3′	23	645	431

[1170]

TABLE ATC
CNS_neurodegeneration_v1.0
	Rel.	Rel.	Rel.		Rel.	Rel.	Rel.
	Exp. (%)	Exp. (%)	Exp. (%)		Exp. (%)	Exp. (%)	Exp. (%)
	Ag1778,	Ag5110,	Ag5110,		Ag1778,	Ag5110,	Ag5110,
	Run	Run	Run		Run	Run	Run
Tissue Name	276596797	226442922	276596798	Tissue Name	276596797	226442922	276596798
AD 1 Hippo	11.7	6.2	5.3	Control	6.6	12.2	17.7
				(Path) 3
				Temporal
				Ctx
AD 2 Hippo	31.4	7.4	20.3	Control	33.4	15.8	13.3
				(Path) 4
				Temporal
				Ctx
AD 3 Hippo	12.5	5.3	4.9	AD 1	23.0	7.7	8.0
				Occipital Ctx
AD 4 Hippo	5.4	9.4	0.0	AD 2	0.0	0.0	0.0
				Occipital Ctx
				(Missing)
AD 5 Hippo	82.4	79.0	45.4	AD 3	12.2	6.2	5.8
				Occipital Ctx
AD 6 Hippo	54.3	88.3	70.2	AD 4	16.3	18.0	7.0
				Occipital Ctx
Control 2	17.9	18.8	19.5	AD 5	77.9	29.9	26.2
Hippo				Occipital Ctx
Control 4	13.0	19.3	13.3	AD 6	36.9	18.9	18.8
Hippo				Occipital Ctx
Control	11.0	7.5	16.3	Control 1	6.2	6.8	5.4
(Path) 3				Occipital Ctx
Hippo
AD 1	20.3	14.6	11.0	Control 2	54.0	44.8	51.4
Temporal				Occipital Ctx
Ctx
AD2	29.9	16.6	21.8	Control 3	32.3	4.9	26.8
Temporal				Occipital Ctx
Ctx
AD 3	11.7	8.4	17.7	Control 4	7.5	9.2	5.3
Temporal				Occipital Ctx
Ctx
AD 4	20.2	5.6	19.6	Control	60.3	24.7	41.8
Temporal				(Path) 1
Ctx				Occipital Ctx
AD 5 Inf	72.2	47.0	46.3	Control	12.8	9.2	6.3
Temporal				(Path) 2
Ctx				Occipital Ctx
AD 5 Sup	39.5	51.1	44.1	Control	5.5	0.9	0.0
Temporal				(Path) 3
Ctx				Occipital Ctx
AD 6 Inf	75.3	84.1	84.1	Control	16.6	15.5	12.3
Temporal				(Path) 4
Ctx				Occipital Ctx
AD 6 Sup	100.0	100.0	100.0	Control 1	10.0	10.0	3.6
Temporal				Parietal Ctx
Ctx
Control 1	11.2	10.4	3.9	Control 2	46.0	57.0	27.5
Temporal				Parietal Ctx
Ctx
Control 2	25.3	21.6	36.3	Control 3	23.5	18.3	16.6
Temporal				Parietal Ctx
Ctx
Control 3	31.2	37.9	38.2	Control	78.5	39.2	52.5
Temporal Ctx				(Path) 1
Ctx				Parietal Ctx
Control 3	11.7	8.4	8.8	Control	23.5	12.5	14.9
Temporal				(Path) 2
Ctx				Parietal Ctx
Control	36.6	53.6	46.7	Control	9.5	13.9	5.8
(Path) 1				(Path) 3
Temporal				Parietal Ctx
Ctx
Control	46.0	29.7	32.5	Control	46.0	58.6	39.2
(Path) 2				(Path) 4
Temporal				Parietal Ctx
Ctx

[1171]

TABLE ATD
General_screening_panel_v1.5
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag5110,		Ag5110,
	Run		Run
Tissue Name	228980585	issue Name	228980585
Adipose	5.4	Renal ca. TK-10	11.7
Melanoma* Hs688(A).T	10.7	Bladder	12.2
Melanoma* Hs688(B).T	5.8	Gastric ca. (liver met.) NCI-N87	3.8
Melanoma* M14	19.5	Gastric ca. KATO III	10.6
Melanoma* LOXIMVI	17.3	Colon ca. SW-948	2.6
Melanoma* SK-MEL-5	29.9	Colon ca. SW480	16.6
Squamous cell carcinoma SCC-4	4.2	Colon ca.* (SW480 met) SW620	10.8
Testis Pool	9.2	Colon ca. HT29	17.0
Prostate ca.* (bone met) PC-3	48.0	Colon ca. HCT-116	6.7
Prostate Pool	0.6	Colon ca. CaCo-2	9.8
Placenta	0.5	Colon cancer tissue	7.1
Uterus Pool	2.3	Colon ca. SW1116	2.5
Ovarian ca. OVCAR-3	5.5	Colon ca. Colo-205	3.5
Ovarian ca. SK-OV-3	11.8	Colon ca. SW-48	4.7
Ovarian ca. OVCAR-4	7.9	Colon Pool	0.8
Ovarian ca. OVCAR-5	17.4	Small Intestine Pool	1.2
Ovarian ca. IGROV-1	8.7	Stomach Pool	2.2
Ovarian ca. OVCAR-8	8.2	Bone Marrow Pool	1.2
Ovary	0.3	Fetal Heart	13.0
Breast ca. MCF-7	4.3	Heart Pool	4.0
Breast ca. MDA-MB-231	25.0	Lymph Node Pool	0.9
Breast ca. BT 549	21.3	Fetal Skeletal Muscle	0.6
Breast ca. T47D	2.7	Skeletal Muscle Pool	1.7
Breast ca. MDA-N	17.2	Spleen Pool	7.5
Breast Pool	0.7	Thymus Pool	11.6
Trachea	21.9	CNS cancer (glio/astro) U87-MG	48.3
Lung	1.2	CNS cancer (glio/astro) U-118-MG	71.7
Fetal Lung	4.0	CNS cancer (neuro; met) SK-N-AS	7.2
Lung ca. NCI-N417	11.3	CNS cancer (astro) SF-539	16.6
Lung ca. LX-1	20.3	CNS cancer (astro) SNB-75	24.7
Lung ca. NCI-H146	5.5	CNS cancer (glio) SNB-19	11.0
Lung ca. SHP-77	17.7	CNS cancer (glio) SF-295	27.5
Lung ca. A549	6.9	Brain (Amygdala) Pool	2.0
Lung ca. NCI-H526	11.9	Brain (cerebellum)	5.2
Lung ca. NCI-H23	4.7	Brain (fetal)	1.0
Lung ca. NCI-H460	32.3	Brain (Hippocampus) Pool	2.0
Lung ca. HOP-62	9.7	Cerebral Cortex Pool	1.9
Lung ca. NCI-H522	12.8	Brain (Substantia nigra) Pool	1.6
Liver	0.4	Brain (Thalamus) Pool	1.7
Fetal Liver	100.0	Brain (whole)	3.0
Liver ca. HepG2	15.4	Spinal Cord Pool	1.0
Kidney Pool	1.6	Adrenal Gland	14.9
Fetal Kidney	2.2	Pituitary gland Pool	0.4
Renal ca. 786-0	10.5	Salivary Gland	6.1
Renal ca. A498	0.2	Thyroid (female)	0.5
Renal ca. ACHN	8.4	Pancreatic ca. CAPAN2	2.6
Renal ca. UO-31	3.7	Pancreas Pool	1.3

[1172]

TABLE ATE
General_screening_panel v1.6
	Rel.	Rel.		Rel.	Rel.
	Exp. (%)	Exp. (%)		Exp. (%)	Exp. (%)
	Ag1778,	Ag5110,		Ag1778,	Ag5110,
	Run	Run		Run	Run
Tissue Name	277218713	277218715	Tissue Name	277218713	277218715
Adipose	8.8	8.7	Renal ca. TK-10	31.6	13.5
Melanoma*	45.1	15.5	Bladder	23.3	14.5
Hs688(A).T
Melanoma*	34.6	11.7	Gastric ca. (liver	22.1	5.0
Hs688(B).T			met.) NCI-N87
Melanoma* M14	29.3	11.6	Gastric ca. KATO	9.0	15.3
			III
Melanoma*	16.6	32.1	Colon ca. SW-948	9.2	4.4
LOXIMVI
Melanoma*	23.0	36.9	Colon ca. SW480	35.8	22.5
SK-MEL-5
Squamous Cell	16.6	7.2	Colon ca.* (SW480	24.0	11.9
carcinoma SCC-4			met) SW620
Testis Pool	8.9	8.5	Colon ca. HT29	32.1	21.5
Prostate ca.* (bone	100.0	50.7	Colon ca. HCT-116	17.9	9.3
met) PC-3
Prostate Pool	5.7	1.7	Colon ca. CaCo-2	21.6	13.5
Placenta	1.6	0.3	Colon cancer tissue	3.2	10.5
Uterus Pool	3.5	3.1	Colon ca. SW1116	3.8	2.7
Ovarian ca.	11.6	9.5	Colon ca. Colo-205	6.7	4.5
OVCAR-3
Ovarian ca. SK-OV-3	33.0	20.3	Colon ca. SW-48	12.1	5.2
Ovarian ca.	11.4	10.7	Colon Pool	6.6	1.8
OVCAR-4
Ovarian ca.	28.1	24.8	Small Intestine Pool	9.0	3.0
OVCAR-5
Ovarian ca.	29.1	12.7	Stomach Pool	5.6	4.5
IGROV-1
Ovarian ca.	15.9	0.1	Bone Marrow Pool	5.1	2.4
OVCAR-8
Ovary	4.4	1.6	Fetal Heart	61.6	26.4
Breast ca. MCF-7	5.9	3.6	Heart Pool	6.8	8.8
Breast ca.	79.0	34.4	Lymph Node Pool	10.4	0.8
MDA-MB-231
Breast ca. BT 549	35.6	15.9	Fetal Skeletal	6.6	0.6
			Muscle
Breast ca. T47D	3.0	3.4	Skeletal Muscle	0.9	0.7
			Pool
Breast ca. MDA-N	20.7	20.9	Spleen Pool	19.2	13.0
Breast Pool	7.4	1.9	Thymus Pool	20.2	12.6
Trachea	23.8	33.7	CNS cancer	47.0	51.1
			(glio/astro)
			U87-MG
Lung	4.6	1.0	CNS cancer	43.2	100.0
			(glio/astro)
			U-118-MG
Fetal Lung	17.4	8.1	CNS cancer	14.1	7.7
			(neuro; met)
			SK-N-AS
Lung ca. NCI-N417	16.2	16.0	CNS cancer (astro)	35.1	28.3
			SF-539
Lung ca. LX-1	38.7	8.8	CNS cancer (astro)	50.3	30.8
			SNB-75
Lung ca. NCI-H146	16.7	5.9	CNS cancer (glio)	34.4	13.1
			SNB-19
Lung ca. SHP-77	53.2	25.9	CNS cancer (glio)	93.3	46.0
			SF-295
Lung ca. A549	10.9	9.9	Brain (Amygdala)	7.7	2.3
			Pool
Lung ca. NCI-H526	10.1	10.9	Brain (cerebellum)	24.7	5.3
Lung ca. NCI-H23	12.2	9.2	Brain (fetal)	9.7	1.3
Lung ca. NCI-H460	57.4	57.8	Brain	9.7	2.8
			(Hippocampus)
			Pool
Lung ca. HOP-62	39.0	9.7	Cerebral Cortex Pool	9.6	3.3
Lung ca. NCI-H522	19.5	13.3	Brain (Substantia	6.0	2.8
			nigra) Pool
Liver	1.5	0.6	Brain (Thalamus)	15.3	1.9
			Pool
Fetal Liver	15.1	6.0	Brain (whole)	9.5	3.3
Liver ca. HepG2	41.5	18.2	Spinal Cord Pool	5.8	2.1
Kidney Pool	9.6	2.0	Adrenal Gland	27.5	23.3
Fetal Kidney	14.7	2.6	Pituitary gland Pool	2.5	1.0
Renal ca. 786-0	14.5	11.0	Salivary Gland	9.8	10.4
Renal ca. A498	2.2	0.9	Thyroid (female)	1.5	1.9
Renal ca. ACHN	9.5	10.8	Pancreatic ca.	9.7	5.3
			CAPAN2
Renal ca. UO-31	13.4	4.6	Pancreas Pool	18.0	7.2

[1173]

TABLE ATF
Panel 1.3D
	Rel.		Rel.
	Exp. (%		Exp. (%)
	Ag1778,		Ag1778,
	Run		Run
Tissue Name	157790405	Tissue Name	157790405
Liver adenocarcinoma	6.7	Kidney (fetal)	12.1
Pancreas	1.3	Renal ca. 786-0	6.8
Pancreatic ca. CAPAN 2	2.1	Renal ca. A498	12.2
Adrenal gland	18.7	Renal ca. RXF 393	15.0
Thyroid	2.9	Renal ca. ACHN	3.2
Salivary gland	6.2	Renal ca. UO-31	8.4
Pituitary gland	5.7	Renal ca. TK-10	3.6
Brain (fetal)	2.5	Liver	3.0
Brain (whole)	4.8	Liver (fetal)	14.7
Brain (amygdala)	6.3	Liver ca. (hepatoblast) HepG2	25.5
Brain (cerebellum)	5.4	Lung	13.7
Brain (hippocampus)	22.8	Lung (fetal)	5.3
Brain (substantia nigra)	1.1	Lung ca. (small cell) LX-1	14.5
Brain (thalamus)	3.3	Lung ca. (small cell) NCI-H69	4.9
Cerebral Cortex	14.7	Lung ca. (s.cell var.) SHP-77	36.1
Spinal cord	2.3	Lung ca. (large cell)NCI-H460	12.9
glio/astro U87-MG	21.6	Lung ca. (non-sm. cell) A549	8.1
glio/astro U-118-MG	56.3	Lung ca. (non-s.cell) NCI-H23	7.3
astrocytoma SW1783	31.2	Lung ca. (non-s.cell) HOP-62	12.8
neuro*; met SK-N-AS	30.4	Lung ca. (non-s.cl) NCI-H522	4.5
astrocytoma SF-539	22.2	Lung ca. (squam.) SW 900	1.5
astrocytoma SNB-75	12.6	Lung ca. (squam.) NCI-H596	0.7
glioma SNB-19	29.9	Mammary gland	9.7
glioma U251	22.2	Breast ca.* (pl.ef) MCF-7	4.6
glioma SF-295	20.3	Breast ca.* (pl.ef) MDA-MB-231	100.0
Heart (fetal)	35.4	Breast ca.* (pl.ef) T47D	5.1
Heart	4.5	Breast ca. BT-549	45.1
Skeletal muscle (fetal)	26.1	Breast ca. MDA-N	28.9
Skeletal muscle	3.1	Ovary	4.0
Bone marrow	13.1	Ovarian ca. OVCAR-3	4.5
Thymus	6.2	Ovarian ca. OVCAR-4	3.5
Spleen	15.5	Ovarian ca. OVCAR-5	13.4
Lymph node	16.3	Ovarian ca. OVCAR-8	3.1
Colorectal	7.9	Ovarian ca. IGROV-1	4.2
Stomach	14.5	Ovarian ca.* (ascites) SK-OV-3	13.2
Small intestine	15.5	Uterus	3.1
Colon ca. SW480	9.7	Placenta	4.3
Colon ca.* SW620(SW480 met)	10.7	Prostate	2.2
Colon ca. HT29	25.5	Prostate ca.* (bone met)PC-3	16.7
Colon ca. HCT-116	5.1	Testis	20.2
Colon ca. CaCo-2	8.1	Melanoma Hs688(A).T	7.1
Colon ca. tissue(ODO3866)	8.4	Melanoma* (met) Hs688(B).T	3.8
Colon ca. HCC-2998	12.2	Melanoma UACC-62	2.0
Gastric ca.* (liver met) NCI-N87	11.1	Melanoma M14	11.4
Bladder	8.0	Melanoma LOX IMVI	10.8
Trachea	17.7	Melanoma* (met) SK-MEL-5	5.2
Kidney	0.7	Adipose	4.9

[1174]

TABLE ATG
Panel 4.1D
	Rel.	Rel.	Rel.	Rel.	Rel.
	Exp. (%)	Exp. (%)	Exp. (%)	Exp. (%)	Exp. (%)
	Ag1778,	Ag1778,	Ag5110,	Ag5110,	Ag5110,
	Run	Run	Run	Run	Run
Tissue Name	276596860	276686878	226444095	276596862	276686880
Secondary Th1 act	23.5	26.8	13.9	14.9	9.0
Secondary Th2 act	28.7	28.1	11.4	14.8	17.9
Secondary Tr1 act	5.4	8.4	7.9	1.9	4.5
Secondary Th1 rest	2.9	3.8	6.3	1.0	1.5
Secondary Th2 rest	7.4	4.3	11.3	4.3	2.7
Secondary Tr1 rest	4.3	4.9	6.6	4.8	1.4
Primary Th1 act	4.5	5.6	13.9	5.0	1.8
Primary Th2 act	23.2	16.8	14.4	14.4	16.5
Primary Tr1 act	22.2	23.3	13.9	11.1	12.3
Primary Th1 rest	3.1	3.3	2.2	0.0	0.0
Primary Th2 rest	6.8	4.2	5.6	0.0	0.0
Primary Tr1 rest	2.6	3.6	10.3	0.7	0.0
CD45RA CD4	25.5	26.4	9.5	18.3	16.2
lymphocyte act
CD45RO CD4	40.1	27.2	22.1	27.9	22.4
lymphocyte act
CD8 lymphocyte act	5.1	7.4	13.1	8.1	2.4
Secondary CD8	3.3	5.1	20.9	32.3	5.1
lymphocyte rest
Secondary CD8	4.3	3.7	3.3	1.3	0.0
lymphocyte act
CD4 lymphocyte none	13.3	8.6	13.7	4 3	4.9
2ry	3.2	5.2	8.1	3.1	2.4
Th1/Th2/Tr1_anti-CD95
CH11
LAK cells rest	13.2	6.7	10.1	5.6	4.6
LAK cells IL-2	9.1	8.0	11.1	6.2	3.5
LAK cells IL-2 + IL-12	0.8	1.3	11.0	1.7	0.0
LAK cells IL-2 + IFN	9.2	8.5	12.2	4.8	7.6
gamma
LAK cells IL-2 + IL-18	6.4	5.1	15.6	3.7	12.2
LAK cells	100.0	100.0	100.0	100.0	100.0
PMA/ionomycin
NK Cells IL-2 rest	27.5	17.8	8.7	7.1	14.7
Two Way MLR 3 day	16.8	21.2	16.3	5.1	10.7
Two Way MLR 5 day	2.9	2.7	4.2	1.7	0.0
Two Way MLR 7 day	6.2	2.6	3.4	1.9	2.6
PBMC rest	3.6	3.7	5.9	2.3	3.2
PBMC PWM	9.5	6.9	4.5	1.7	1.6
PBMC PHA-L	6.9	8.0	8.7	5.0	3.4
Ramos (B cell) none	7.7	4.2	4.7	0.6	1.4
Ramos (B cell) ionomycin	36.6	32.1	11.9	9.2	6.0
B lymphocytes PWM	11.7	4.9	6.7	4.4	4.3
B lymphocytes CD40L	34.2	21.0	13.2	15.2	19.8
and IL-4
EOL-1 dbcAMP	52.1	34.4	11.0	10.8	15.6
EOL- 1 dbcAMP	9.8	6.0	3.5	1.4	5.8
PMA/ionomycin
Dendritic cells none	9.5	7.7	7.3	6.3	5.4
Dendritic cells LPS	5.6	5.0	6.6	1.1	2.0
Dendritic cells anti-CD40	3.6	4.2	7.0	1.3	1.5
Monocytes rest	4.9	3.1	6.9	1.2	0.0
Monocytes LPS	11.3	8.4	6.8	2.9	0.0
Macrophages rest	5.7	10.2	5.7	1.9	0.0
Macrophages LPS	3.2	3.0	5.2	0.7	3.6
HUVEC none	6.0	4.2	1.8	1.3	5.2
HUVEC starved	11.0	9.5	4.4	5.9	2.3
HUVEC IL-1beta	11.9	10.1	4.9	8.1	9.0
HUVEC IFN gamma	9.2	9.4	5.5	2.7	6.5
HUVEC TNF alpha + IFN	3.8	3.6	4.1	3.5	1.8
gamma
HUVEC TNF alpha + IL4	2.7	2.8	5.5	0.0	0.0
HUVEC IL-11	4.3	5.3	3.5	3.4	0.0
Lung Microvascular EC	25.3	23.3	7.5	6.9	6.2
none
Lung Microvascular EC	9.2	7.0	7.9	2.6	2.2
TNF alpha + IL-1beta
Microvascular Dermal EC	1.8	2.1	3.8	0.0	0.0
none
Microvasular Dermal EC	2.0	2.6	1.9	1.3	0.0
TNF alpha + IL-1beta
Bronchial epithelium	8.8	14.0	10.6	3.3	3.3
TNF alpha + IL1beta
Small airway epithelium	10.7	3.0	2.4	3.4	6.0
none
Small airway epithelium	31.9	31.0	21.9	30.4	15.8
TNF alpha + IL-1beta
Coronery artery SMC rest	25.2	19.6	9.1	13.3	13.4
Coronery artery SMC	27.5	19.6	5.5	7.8	15.2
TNF alpha + IL-1beta
Astrocytes rest	8.2	15.3	2.4	1.9	2.8
Astrocytes TNF alpha +	5.2	2.7	3.4	0.0	5.3
IL-1beta
KU-812 (Basophil) rest	10.7	8.1	3.5	2.0	0.0
KU-812 (Basophil)	37.1	25.5	11.6	8.9	5.2
PMA/ionomycin
CCD1106 (Keratinocytes)	20.6	20.9	13.2	4.5	6.9
none
CCD11O6 (Keratinocytes)	14.1	22.7	17.8	7.7	2.3
TNF alpha + IL-1beta
Liver cirrhosis	11.4	8.5	7.4	1.4	1.4
NCI-H292 none	12.9	7.6	7.1	5.5	7.5
NCI-H292 IL-4	11.9	12.2	4.3	4.8	5.8
NCI-H292 IL-9	16.8	12.7	7.0	3.7	11.4
NCI-H292 IL-13	12.5	10.0	6.5	4.2	7.3
NCI-H292 IFN gamma	3.9	4.1	7.6	2.6	4.2
HPAEC none	1.7	2.9	2.6	0.0	0.0
HPAEC TNF alpha + IL-1	10.6	7.2	2.9	2.7	3.3
beta
Lung fibroblast none	31.2	24.1	4.5	8.7	5.8
Lung fibroblast TNF	24.3	21.6	6.6	7.5	11.2
alpha + IL-1beta
Lung fibroblast IL-4	6.5	1.1	1.8	3.2	4.0
Lung fibroblast IL-9	19.2	28.3	8.2	6.7	7.7
Lung fibroblast IL-13	8.2	5.1	2.9	0.0	3.6
Lung fibroblast IFN	15.3	14.9	5.5	3.8	12.9
gamma
Dermal fibroblast	25.0	23.3	7.8	4.6	11.0
CCD1070 rest
Dermal fibroblast	74.2	45.1	14.1	23.2	36.3
CCD1070 TNF alpha
Dermal fibroblast	23.3	22.4	4.3	3.9	5.7
CCD1070 IL-1beta
Dermal fibroblast IFN	3.4	3.9	2.0	0.9	0.0
gamma
Dermal fibroblast IL-4	6.8	8.2	3.3	2.6	3.0
Dermal Fibroblasts rest	11.2	7.8	2.8	2.7	3.8
Neutrophils TNFa + LPS	4.5	1.6	1.6	1.8	0.0
Neutrophils rest	28.9	31.2	12.1	15.9	20.2
Colon	2.3	1.5	2.3	0.0	2.3
Lung	2.0	2.4	3.7	0.9	1.6
Thymus	13.0	14.6	6.6	0.0	5.1
Kidney	7.9	7.5	1.7	1.1	2.8

[1175]

TABLE ATH
general oncology screening panel_v_2.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag5110,		Ag5110,
	Run		Run
Tissue Name	259939210	Tissue Nme	259939210
Colon cancer 1	6.5	Bladder NAT 2	0.0
Colon NAT 1	5.9	Bladder NAT 3	0.0
Colon cancer 2	6.0	Bladder NAT 4	0.0
Colon NAT 2	14.2	Prostate adenocarcinoma 1	1.2
Colon cancer 3	23.7	Prostate adenocarcinoma 2	0.0
Colon NAT 3	15.7	Prostate adenocarcinoma 3	1.6
Colon malignant cancer 4	41.5	Prostate adenocarcinoma 4	14.2
Colon NAT 4	4.2	Prostate NAT 5	0.9
Lung cancer 1	7.5	Prostate adenocarcinoma 6	0.0
Lung NAT 1	0.0	Prostate adenocarcinoma 7	0.7
Lung cancer 2	28.5	Prostate adenocarcinoma 8	0.0
Lung NAT 2	1.2	Prostate adenocarcinoma 9	3.0
Squamous cell carcinoma 3	42.3	Prostate NAT 10	0.0
Lung NAT 3	0.0	Kidney cancer 1	34.2
Metastatic melanoma 1	1.4	Kidney NAT 1	4.5
Melanoma 2	10.4	Kidney cancer 2	100.0
Melanoma 3	2.1	Kidney NAT 2	3.2
Metastatic melanoma 4	2.2	Kidney cancer 3	19.6
Metastatic melanoma 5	4.5	Kidney NAT 3	1.1
Bladder cancer 1	0.0	Kidney cancer 4	37.1
Bladder NAT 1	0.0	Kidney NAT 4	1.0
Bladder cancer 2	2.3

[1176] CNS_neurodegeneration_v1.0 Summary: Ag1778/Ag5110 This panel confirms the expression of this gene at low levels in the brains of an independent group of individuals. However, no differential expression of this gene was detected between Alzheimer's diseased postmortem brains and those of non-demented controls in this experiment. Please see Panel 1.5 for a discussion of this gene in treatment of central nervous system disorders.

[1177] General_screen_panel_v1.5 Summary: Ag5110 Highest expression of this gene is detected in fetal liver (CT=29.4). Interestingly, this gene is expressed at much higher levels in fetal when compared to adult liver (CT=37). This observation suggests that expression of this gene can be used to distinguish fetal from adult liver. 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 protein encoded by this gene could be useful in treatment of liver related diseases.

[1178] Among tissues with metabolic or endocrine function, this gene is expressed at low levels in adipose, adrenal gland, heart, fetal liver and stomach. This gene codes for a splice variant of pyruvate dehydrogenase [lipoamide] kinase (PDK). Pyruvate dehydrogenase kinase (PDK) catalyzes phosphorylation and inactivation of the pyruvate dehydrogenase complex (PDC). Inactivation of PDC by increased PDK activity promotes gluconeogenesis by conserving three-carbon substrates. This helps maintain glucose levels during starvation, but is detrimental in diabetes (Huang et al., 2002, Diabetes 51(2):276-83, PMID: 11812733). Therefore, therapeutic modulation of the activity of PKD encoded by gene may be useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[1179] In addition, this gene is expressed at low levels in cerebellum and whole brain. Therefore, therapeutic modulation of this gene product may be useful in the treatment of neurological disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[1180] Moderate to low 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.

[1181] General_screen_panel_v1.6 Summary: Ag1778/Ag5110 Two experiments with different probe and primer sets are in good agreement. Highest expression of this gene is detected in a prostate cancer PC3 and a brain cancer U-118-MG cell lines (CTs=25-29.8). Expression in this panel correlates with pattern seen in panel 1.5. Moderate to low levels of expression of this gene is detected in tissues with metabolic/endocrine functions such as pancreas, adipose, adrenal gland, heart, fetal liver and gastrointestinal tract, in brain including cerebellum, cerebral cortex, substantia nigra and the whole brain and also in number of cancer cell lines derived from pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers. Please see panel 1.5 for further discussion on the utility of this gene.

[1182] Panel 1.3D Summary: Ag1778 Highest expression of this gene is detected in a breast cancer cell line (CT=27.4). Expression in this panel correlates with pattern seen in panel 1.5. Moderate to low levels of expression of this gene is detected in tissues with metabolic/endocrine functions such as pancreas, adrenal gland, heart, fetal liver and gastrointestinal tract, in brain including cerebellum, cerebral cortex, substantia nigra and the whole brain and also in number of cancer cell lines derived from pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers. Please see panel 1.5 for further discussion of this gene.

[1183] Panel 4.1D Summary: Ag1778/Ag5110 Five experiments with the two different probe-primer sets are in good agreement. Highest expression of this gene is detected in PMA/ionomycin treated LAK cells. These cells are involved in tumor immunology and cell clearance of virally and bacterial infected cells as well as tumors. Therefore, modulation of the function of the protein encoded by this gene through the application of a small molecule drug or antibody may alter the functions of these cells and lead to improvement of symptoms associated with these conditions.

[1184] Low levels of expression of this gene is also seen in naive and memory T cells, resting secondary CD8 lymphocytes, cytokine activated small airway epithelium, and resting neutrophils. Therefore, therapeutic modulation of this gene or its protein product may be useful in the treatment of 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

[1185] General oncology screening panel_v—2.4 Summary: Ag5110 Highest expression of this gene is detected in kidney cancer (CT=32). Low levels of expression of this gene is also seen in colon, lung, prostate and kidney cancer. Higher levels of expression of this gene is associated with cancer as compared to corresponding normal tissue. Therefore, expression of this gene may be used as diagnostic marker for the detection of these cancers.

[1186] Furthermore, therapeutic modulation of this gene or its protein product may be useful in the treatment of colon, lung, prostate and kidney cancers.

[1187] AU. CG96736-01: Neutral amino acid transporter B.

[1188] Expression of gene CG96736-01 was assessed using the primer-probe sets Ag3788 and Ag4075, described in Tables AUA and AUB. Results of the RTQ-PCR runs are shown in Tables AUC, AUD, AUE, AUF, AUG, AUH, AUI, AUJ and AUK.

TABLE AUA
Probe Name Ag3788
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-cgagaaatatcttcccttccaa-3′	22	1182	432
Probe	TET-5′-tgtcagcagcctttcgctcatactct-3′-TAMRA	26	1209	433
Reverse	5′-ttccggtgatattcctctcttc-3′	22	1244	434

[1189]

TABLE AUB
Probe Name Ag4075
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-cgagaaatatcttcccttccaa-3′	22	1182	435
Probe	TET-5′-tgtcagcagcctttcgctcatactct-3′-TAMRA	26	1209	436
Reverse	5′-ttccggtgatattcctctcttc-3′	22	1244	437

[1190]

TABLE AUC
AI_comprehensive panel_v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4075,		Ag4075,
	Run		Run
Tissue Name	226203371	issue Name	226203371
110967 COPD-F	6.0	112427 Match Control Psoriasis-F	12.3
110980 COPD-F	9.9	112418 Psoriasis-M	3.6
110968 COPD-M	6.6	112723 Match Control Psoriasis-M	6.3
110977 COPD-M	0.0	112419 Psoriasis-M	6.5
110989 Emphysema-F	8.7	112424 Match Control Psoriasis-M	2.7
110992 Emphysema-F	12.3	112420 Psoriasis-M	14.1
110993 Emphysema-F	7.2	112425 Match Control Psoriasis-M	6.7
110994 Emphysema-F	4.6	104689 (MF) OA Bone-Backus	21.6
110995 Emphysema-F	20.3	104690 (MF) Adj “Normal”	21.8
		Bone-Backus
110996 Emphysema-F	7.1	104691 (MF) OA Synovium-Backus	14.1
110997 Asthma-M	2.5	104692 (BA) OA Cartilage-Backus	53.6
111001 Asthma-F	6.7	104694 (BA) OA Bone-Backus	14.8
111002 Asthma-F	5.7	104695 (BA) Adj “Normal”	28.7
111003 Atopic Asthma-F	11.0	104696 (BA) OA Synovium-Backus	15.8
111004 Atopic Asthma-F	13.3	104700 (SS) OA Bone-Backus	11.6
111005 Atopic Asthma-F	12.2	104701 (SS) Adj “Normal”	12.7
		Bone-Backus
111006 Atopic Asthma-F	2.6	104702 (SS) OA Synovium-Backus	27.5
111417 Allergy-M	7.6	117093 OA Cartilage Rep7	6.3
112347 Allergy-M	0.0	112672 OA Bone5	6.0
112349 Normal Lung-F	0.0	112673 OA Synovium5	1.4
112357 Normal Lung-F	19.9	112674 OA Synovial Fluid cells5	3.0
112354 Normal Lung-M	4.0	117100 OA Cartilage Rep14	4.0
112374 Crohns-F	2.7	112756 OA Bone9	100.0
112389 Match Control Crohns-F	9.3	112757 OA Synovium9	0.9
112375 Crohns-F	2.0	112758 OA Synovial Fluid Cells9	3.8
112732 Match Control Crohns-F	12.6	117125 RA Cartilage Rep2	9.0
112725 Crohns-M	0.3	113492 Bone2 RA	8.1
112387 Match Control	5.0	113493 Synovium2 RA	2.5
Crohns-M
112378 Crohns-M	0.0	113494 Syn Fluid Cells RA	5.3
112390 Match Control	6.0	113499 Cartilage4 RA	6.7
Crohns-M
112726 Crohns-M	9.9	113500 Bone4 RA	7.0
112731 Match Control	8.1	113501 Synovium4 RA	4.4
Crohns-M
112380 Ulcer Col-F	6.0	113502 Syn Fluid Cells4 RA	3.2
112734 Match Control Ulcer	21.0	113495 Cartilage3 RA	6.3
Col-F
112384 Ulcer Col-F	14.1	113496 Bone3 RA	8.4
112737 Match Control Ulcer	3.4	113497 Synovium3 RA	5.1
Col-F
112386 Ulcer Col-F	3.4	113498 Syn Fluid Cells3 RA	7.9
112738 Match Control Ulcer	18.0	117106 Normal Cartilage Rep20	8.7
Col-F
112381 Ulcer Col-M	0.0	113663 Bone3 Normal	0.0
112735 Match Control Ulcer	0.5	113664 Synovium3 Normal	0.0
Col-M
112382 Ulcer Col-M	7.1	113665 Syn Fluid Cells3 Normal	0.0
112394 Match Control Ulcer	1.6	117107 Normal Cartilage Rep22	1.8
Col-M
112383 Ulcer Col-M	13.1	113667 Bone4 Normal	2.4
112736 Match Control Ulcer	3.8	113668 Synovium4 Normal	1.7
Col-M
112423 Psoriasis-F	6.3	113669 Syn Fluid Cells4 Normal	3.9

[1191]

TABLE AUD
CNS_neurodegeneration_v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4075,		Ag4075,
	Run		Run
Tissue Name	214294982	issue Name	214294982
AD 1 Hippo	11.0	Control (Path) 3 Temporal Ctx	1.0
AD 2 Hippo	8.4	Control (Path) 4 Temporal Ctx	1.7
AD 3 Hippo	8.0	AD 1 Occipital Ctx	6.5
AD 4 Hippo	2.9	AD 2 Occipital Ctx (Missing)	0.0
AD 5 Hippo	16.8	AD 3 Occipital Ctx	1.3
AD 6 Hippo	100.0	AD 4 Occipital Ctx	3.6
Control 2 Hippo	19.6	AD 5 Occipital Ctx	11.9
Control 4 Hippo	17.6	AD 6 Occipital Ctx	6.5
Control (Path) 3 Hippo	3.0	Control 1 Occipital Ctx	5.6
AD 1 Temporal Ctx	6.3	Control 2 Occipital Ctx	10.4
AD 2 Temporal Ctx	14.1	Control 3 Occipital Ctx	6.0
AD 3 Temporal Ctx	4.2	Control 4 Occipital Ctx	2.9
AD 4 Temporal Ctx	7.5	Control (Path) 1 Occipital Ctx	3.3
AD 5 Inf Temporal Ctx	8.9	Control (Path) 2 Occipital Ctx	0.5
AD 5 Sup Temporal Ctx	24.5	Control (Path) 3 Occipital Ctx	1.6
AD 6 Inf Temporal Ctx	78.5	Control (Path) 4 Occipital Ctx	0.4
AD 6 Sup Temporal Ctx	56.6	Control 1 Parietal Ctx	5.9
Control 1 Temporal Ctx	2.3	Control 2 Parietal Ctx	9.9
Control 2 Temporal Ctx	12.1	Control 3 Parietal Ctx	6.0
Control 3 Temporal Ctx	7.7	Control (Path) 1 Parietal Ctx	3.6
Control 3 Temporal Ctx	3.1	Control (Path) 2 Parietal Ctx	1.1
Control (Path) 1 Temporal Ctx	4.6	Control (Path) 3 Parietal Ctx	2.2
Control (Path) 2 Temporal Ctx	1.8	Control (Path) 4 Parietal Ctx	3.4

[1192]

TABLE AUE
General_screening_panel_v1.4
	Rel.	Rel.		Rel.	Rel.
	Exp. (%)	Exp. (%)		Exp. (%)	Exp. (%)
	Ag4075,	Ag4075,		Ag4075,	Ag4075,
	Run	Run		Run	Run
Tissue Name	212696066	218525356	Tissue Name	212696066	218525356
Adipose	0.0	1.3	Renal ca. TK-10	9.7	14.8
Melanoma*	14.4	23.2	Bladder	1.0	1.8
Hs688(A).T
Melanoma*	19.1	29.9	Gastric ca. (liver	41.5	42.0
Hs688(B).T			met.) NCI-N87
Melanoma* M14	9.5	12.7	Gastric ca. KATO	25.5	22.8
			III
Melanoma*	8.1	12.9	Colon ca. SW-948	4.4	5.6
LOXIMVI
Melanoma*	5.9	14.2	Colon ca. SW480	100.0	100.0
SK-MEL-5
Squamous cell	5.1	10.2	Colon ca.* (SW480	41.5	50.0
carcinoma SCC-4			met) SW620
Testis Pool	1.4	1.9	Colon ca. HT29	10.2	13.6
Prostate ca.* (bone	9.5	13.6	Colon ca. HCT-116	13.0	20.9
met) PC-3
Prostate Pool	1.1	1.5	Colon ca. CaCo-2	12.0	14.5
Placenta	1.1	1.3	Colon cancer tissue	5.0	8.4
Uterus Pool	0.1	0.2	Colon ca. SW1116	14.7	15.9
Ovarian ca.	6.5	8.0	Colon ca. Colo-205	24.7	29.5
OVCAR-3
Ovarian ca. SK-OV-3	8.1	9.9	Colon ca. SW-48	3.6	4.7
Ovarian ca.	9.2	16.4	Colon Pool	0.7	1.1
OVCAR-4
Ovarian ca.	28.1	32.1	Small Intestine Pool	0.5	0.6
OVCAR-5
Ovarian ca.	23.0	33.2	Stomach Pool	0.8	0.8
IGROV-1
Ovarian ca.	10.3	16.4	Bone Marrow Pool	0.2	0.4
OVCAR-8
Ovary	0.5	0.8	Fetal Heart	0.1	0.1
Breast ca. MCF-7	15.7	17.2	Heart Pool	0.2	0.3
Breast ca.	10.4	15.6	Lymph Node Pool	1.2	1.0
MDA-MB-231
Breast ca. BT 549	9.9	18.7	Fetal Skeletal	0.2	0.2
			Muscle
Breast ca. T47D	53.2	51.8	Skeletal Muscle	0.2	0.3
			Pool
Breast ca. MDA-N	4.7	6.3	Spleen Pool	0.7	0.5
Breast Pool	0.6	0.6	Thymus Pool	0.8	0.9
Trachea	3.6	5.3	CNS cancer	20.0	20.3
			(glio/astro)
			U87-MG
Lung	0.1	0.1	CNS cancer	11.2	12.9
			(glio/astro)
			U-118-MG
Fetal Lung	2.4	4.0	CNS cancer	6.9	8.9
			(neuro; met)
			SK-N-AS
Lung ca. NCI-N417	1.6	0.0	CNS cancer (astro)	9.3	12.0
			SF-539
Lung ca. LX-1	81.8	82.4	CNS cancer (astro)	36.1	55.5
			SNB-75
Lung ca. NCI-H146	0.4	0.8	CNS cancer (glio)	30.1	37.6
			SNB-19
Lung ca. SHP-77	6.8	8.5	CNS cancer (glio)	58.6	60.7
			SF-295
Lung ca. A549	9.8	15.8	Brain (Amygdala)	0.0	0.1
			Pool
Lung ca. NCI-H526	2.1	2.5	Brain (cerebellum)	0.1	0.2
Lung ca. NCI-H23	4.3	4.2	Brain (fetal)	0.2	0.3
Lung ca. NCI-H460	9.2	16.2	Brain	0.1	0.1
			(Hippocampus)
			Pool
Lung ca. HOP-62	4.4	4.5	Cerebral Cortex	0.0	0.1
			Pool
Lung ca. NCI-H522	9.5	10.0	Brain (Substantia	0.1	0.1
			nigra) Pool
Liver	0.0	0.1	Brain (Thalamus)	0.0	0.1
			Pool
Fetal Liver	2.9	4.3	Brain (whole)	0.2	0.2
Liver ca. HepG2	6.7	7.9	Spinal Cord Pool	0.2	0.3
Kidney Pool	1.1	1.2	Adrenal Gland	0.3	0.6
Fetal Kidney	0.3	0.5	Pituitary gland Pool	0.1	0.3
Renal ca. 786-0	5.1	9.5	Salivary Gland	3.0	2.8
Renal ca. A498	3.1	5.0	Thyroid (female)	0.1	0.1
Renal ca. ACHN	5.1	5.9	Pancreatic ca.	7.9	12.2
			CAPAN2
Renal ca. UO-31	2.6	4.2	Pancreas Pool	1.3	1.2

[1193]

TABLE AUF
General_screening_panel_v1.5
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4075,		Ag4075,
	Run		Run
Tissue Name	228714883	issue Name	228714883
Adipose	1.0	Renal ca. TK-10	9.8
Melanoma* Hs688(A).T	18.0	Bladder	1.4
Melanoma* Hs688(B).T	17.4	Gastric ca. (liver met.) NCI-N87	35.4
Melanoma* M14	9.5	Gastric ca. KATO III	19.9
Melanoma* LOXIMVI	9.0	Colon ca. SW-948	4.4
Melanoma* SK-MEL-5	8.7	Colon ca. SW480	100.0
Squamous cell carcinoma SCC-4	5.8	Colon ca.* (SW480 met) SW620	32.8
Testis Pool	1.2	Colon ca. HT29	9.9
Prostate ca.* (bone met) PC-3	10.8	Colon ca. HCT-116	15.2
Prostate Pool	1.5	Colon ca. CaCo-2	11.1
Placenta	1.1	Colon cancer tissue	5.1
Uterus Pool	0.3	Colon ca. SW1116	7.2
Ovarian ca. OVCAR-3	6.2	Colon ca. Colo-205	23.7
Ovarian ca. SK-OV-3	7.5	Colon ca. SW-48	3.2
Ovarian ca. OVCAR-4	12.5	Colon Pool	0.7
Ovarian ca. OVCAR-5	20.2	Small Intestine Pool	0.4
Ovarian ca. IGROV-1	23.8	Stomach Pool	0.7
Ovarian ca. OVCAR-8	11.2	Bone Marrow Pool	0.2
Ovary	0.6	Fetal Heart	0.1
Breast ca. MCF-7	14.4	Heart Pool	0.2
Breast ca. MDA-MB-231	14.1	Lymph Node Pool	0.7
Breast ca. BT 549	8.4	Fetal Skeletal Muscle	0.2
Breast ca. T47D	2.1	Skeletal Muscle Pool	0.4
Breast ca. MDA-N	3.6	Spleen Pool	0.3
Breast Pool	0.5	Thymus Pool	0.5
Trachea	4.6	CNS cancer (glio/astro) U87-MG	12.5
Lung	0.1	CNS cancer (glio/astro) U-118-MG	8.5
Fetal Lung	2.6	CNS cancer (neuro; met) SK-N-AS	5.5
Lung ca. NCI-N417	1.9	CNS cancer (astro) SF-539	8.4
Lung ca. LX-1	81.8	CNS cancer (astro) SNB-75	13.1
Lung ca. NCI-H146	0.6	CNS cancer (glio) SNB-19	27.2
Lung ca. SHP-77	7.7	CNS cancer (glio) SF-295	53.2
Lung ca. A549	11.8	Brain (Amygdala) Pool	0.0
Lung ca. NCI-H526	2.1	Brain (cerebellum)	0.1
Lung ca. NCI-H23	3.5	Brain (fetal)	0.2
Lung ca. NCI-H460	8.8	Brain (Hippocampus) Pool	0.0
Lung ca. HOP-62	3.5	Cerebral Cortex Pool	0.1
Lung ca. NCI-H522	7.5	Brain (Substantia nigra) Pool	0.1
Liver	0.0	Brain (Thalamus) Pool	0.1
Fetal Liver	2.9	Brain (whole)	0.2
Liver ca. HepG2	6.2	Spinal Cord Pool	0.1
Kidney Pool	0.8	Adrenal Gland	0.4
Fetal Kidney	0.3	Pituitary gland Pool	0.2
Renal ca. 786-0	5.6	Salivary Gland	2.7
Renal ca. A498	3.4	Thyroid (female)	0.1
Renal ca. ACHN	4.9	Pancreatic ca. CAPAN2	9.7
Renal ca. UO-31	2.4	Pancreas Pool	0.8

[1194]

TABLE AUG
Panel 3D
	Rel.		Rel.
	Exp. ()		Exp. (%)
	Ag4075,		Ag4075,
	Run		Run
Tissue Name	186579982	Tissue Name	186579982
Daoy-Medulloblastoma	1.7	Ca Ski-Cervical epidermoid	9.3
		carcinoma (metastasis)
TE671-Medulloblastoma	1.3	ES-2-Ovarian clear cell carcinoma	4.2
D283 Med-Medulloblastoma	13.6	Ramos-Stimulated with	12.2
		PMA/ionomycin 6 h
PFSK-1-Primitive	8.0	Ramos-Stimulated with	12.2
Neuroectodermal		PMA/ionomycin 14 h
XF-498-CNS	5.1	MEG-01-Chronic myelogenous	25.0
		leukemia (megokaryoblast)
SNB-78-Glioma	12.9	Raji-Burkitt's lymphoma	2.4
SF-268-Glioblastoma	5.4	Daudi-Burkitt's lymphoma	5.0
T98G-Glioblastoma	7.9	U266-B-cell plasmacytoma	9.3
SK-N-SH-Neuroblastoma	4.4	CA46-Burkitt's lymphoma	2.6
(metastasis)
SF-295-Glioblastoma	8.2	RL-non-Hodgkin's B-cell	6.5
		lymphoma
Cerebellum	0.1	JM1-pre-B-cell lymphoma	6.0
Cerebellum	0.1	Jurkat-T cell leukemia	7.6
NCI-H292-Mucoepidermoid	12.0	TF-1-Erythroleukemia	17.6
lung carcinoma
DMS-114-Small cell lung cancer	3.0	HUT 78-T-cell lymphoma	4.9
DMS-79-Small cell lung cancer	92.0	U937-Histiocytic lymphoma	17.9
NCI-H146-Small cell lung	1.6	KU-812-Myelogenous leukemia	15.4
cancer
NCI-H526-Small cell lung	10.7	769-P-Clear cell renal carcinoma	5.8
cancer
NCI-N417-Small cell lung	3.0	Caki-2-Clear cell renal carcinoma	5.5
cancer
NCI-H82-Small cell lung cancer	5.7	SW 839-Clear cell renal carcinoma	6.2
NCI-H157-Squamous cell lung	30.1	G401-Wilms' tumor	3.8
cancer (metastasis)
NCI-H1155-Large cell lung	9.5	Hs766T-Pancreatic carcinoma (LN	7.6
cancer		metastasis)
NCI-H1299-Large cell lung	6.1	CAPAN-1-Pancreatic	3.3
cancer		adenocarcinoma (liver metastasis)
NCI-H727-Lung carcinoid	8.7	SU86.86-Pancreatic carcinoma	5.1
		(liver metastasis)
NCI-UMC-11-Lung carcinoid	14.4	BxPC-3-Pancreatic	11.4
		adenocarcinoma
LX-1-Small cell lung cancer	100.0	HPAC-Pancreatic adenocarcinoma	6.1
Colo-205-Colon cancer	49.3	MIA PaCa-2-Pancreatic carcinoma	1.1
KM12-Colon cancer	12.7	CFPAC-1-Pancreatic ductal	10.4
		adenocarcinoma
KM20L2-Colon cancer	11.7	PANC-1-Pancreatic epithelioid	4.3
		ductal carcinoma
NCI-H716-Colon cancer	10.2	T24-Bladder carcinma (transitional	1.5
		cell)
SW-48-Colon adenocarcinoma	6.7	5637-Bladder carcinoma	2.8
SW1116-Colon adenocarcinoma	20.9	HT-1197-Bladder carcinoma	10.4
LS 174T-Colon adenocarcinoma	13.4	UM-UC-3-Bladder carcinma	1.4
		(transitional cell)
SW-948-Colon adenocarcinoma	0.9	A204-Rhabdomyosarcoma	2.6
SW-480-Colon adenocarcinoma	3.5	HT-1080-Fibrosarcoma	4.7
NCI-SNU-5-Gastric carcinoma	34.6	MG-63-Osteosarcoma	8.1
KATO III-Gastric carcinoma	38.7	SK-LMS-1-Leiomyosarcoma	8.1
		(vulva)
NCI-SNU-16-Gastric carcinoma	2.9	SJRH30-Rhabdomyosarcoma (met	1.9
		to bone marrow)
NCI-SNU-1-Gastric carcinoma	22.4	A431-Epidermoid carcinoma	10.6
RF-1-Gastric adenocarcinoma	1.8	WM266-4-Melanoma	5.5
RF-48-Gastric adenocarcinoma	1.9	DU 145-Prostate carcinoma (brain	0.1
		metastasis)
MKN-45-Gastric carcinoma	12.0	MDA-MB-468-Breast	13.4
		adenocarcinoma
NCI-N87-Gastric carcinoma	24.5	SCC-4-Squamous cell carcinoma of	0.2
		tongue
OVCAR-5-Ovarian carcinoma	2.3	SCC-9-Squamous cell carcinoma of	0.2
		tongue
RL95-2-Uterine carcinoma	8.3	SCC-15-Squamous cell carcinoma	0.3
		of tongue
HelaS3-Cervical	2.3	CAL 27-Squamous cell carcinoma	10.7
adenocarcinoma		of tongue

[1195]

TABLE AUH
Panel 4.1D
	Rel.		Rel.
	Exp. (%		Exp. (%)
	Ag4075,		Ag4075,
	Run		Run
Tissue Name	184565261	Tissue Name	184565261
Secondary Th1 act	81.2	HUVEC IL-1beta	35.1
Secondary Th2 act	84.1	HUVEC IFN gamma	17.6
Secondary Tr1 act	67.8	HUVEC TNF alpha + IFN gamma	24.7
Secondary Th1 rest	3.5	HUVEC TNF alpha + IL4	29.9
Secondary Th2 rest	11.3	HUVEC IL-11	12.4
Secondary Tr1 rest	3.6	Lung Microvascular EC none	33.4
Primary Th1 act	43.2	Lung Microvascular EC TNF alpha + IL-1beta	21.0
Primary Th2 act	55.1	Microvascular Dermal EC none	20.3
Primary Tr1 act	51.8	Microsvasular Dermal EC	11.7
		TNF alpha + IL-1beta
Primary Th1 rest	3.3	Bronchial epithelium TNF alpha + IL1beta	39.8
Primary Th2 rest	2.2	Small airway epithelium none	10.8
Primary Tr1 rest	10.3	Small airway epithelium TNF alpha + IL-1beta	15.3
CD45RA CD4 lymphocyte act	52.5	Coronery artery SMC rest	34.6
CD45RO CD4 lymphocyte act	45.7	Coronery artery SMC TNF alpha + IL-1beta	32.5
CD8 lymphocyte act	51.1	Astrocytes rest	10.9
Secondary CD8 lymphocyte rest	41.5	Astrocytes TNF alpha + IL-1beta	7.1
Secondary CD8 lymphocyte act	36.1	KU-812 (Basophil) rest	52.1
CD4 lymphocyte none	0.6	KU-812 (Basophil)	82.4
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	4.0	CCD1106 (Keratinocytes) none	52.9
CH11
LAK cells rest	24.1	CCD1106 (Keratinocytes)	39.8
		TNF alpha + IL-1beta
LAK cells IL-2	34.6	Liver cirrhosis	2.8
LAK cells IL-2 + IL-12	28.3	NCI-H292 none	27.0
LAK cells IL-2 + IFN gamma	20.4	NCI-H292 IL-4	53.6
LAK cells IL-2 + IL-18	29.5	NCI-H292 IL-9	29.5
LAK cells PMA/ionomycin	49.0	NCI-H292 IL-13	51.4
NK Cells IL-2 rest	43.2	NCI-H292 IFN gamma	58.6
Two Way MLR 3 day	22.4	HPAEC none	10.4
Two Way MLR 5 day	39.8	HPAEC TNF alpha + IL-1beta	17.0
Two Way MLR 7 day	25.9	Lung fibroblast none	42.0
PBMC rest	2.3	Lung fibroblast TNF alpha + IL-1	17.7
		beta
PBMC PWM	42.3	Lung fibroblast IL-4	36.6
PBMC PHA-L	30.1	Lung fibroblast IL-9	38.4
Ramos (B cell) none	57.4	Lung fibroblast IL-13	41.2
Ramos (B cell) ionomycin	100.0	Lung fibroblast IFN gamma	39.5
B lymphocytes PWM	31.2	Dermal fibroblast CCD1070 rest	84.7
B lymphocytes CD40L and IL-4	14.5	Dermal fibroblast CCD1070 TNF	59.0
		alpha
EOL-1 dbcAMP	61.1	Dermal fibroblast CCD1070 IL-1	55.1
		beta
EOL-1 dbcAMP	21.2	Dermal fibroblast IFN gamma	16.7
PMA/ionomycin
Dendritic cells none	28.5	Dermal fibroblast IL-4	36.9
Dendritic cells LPS	7.9	Dermal fibroblast rest	15.0
Dendritic cells anti-CD40	32.8	Neutrophils TNFa + LPS	1.6
Monocytes rest	11.0	Neutrophils rest	0.4
Monocytes LPS	5.4	Colon	4.5
Macrophages rest	25.5	Lung	7.5
Macrophages LPS	3.7	Thymus	6.3
HUVEC none	21.9	Kidney	12.9
HUVEC starved	27.7

[1196]

TABLE AUI
Panel 5 Islet
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4075,		Ag4075,
	Run		Run
Tissue Name	186511155	Tissue Name	186511155
97457_Patient-02go_adipose	7.6	94709_Donor 2 AM - A_adipose	45.7
97476_Patient-07sk_skeletal	2.9	94710_Donor 2 AM - B_adipose	27.4
muscle
97477_Patient-07ut_uterus	3.5	94711_Donor 2 AM - C_adipose	15.2
97478_Patient-07pl_placenta	5.0	94712_Donor 2 AD - A_adipose	62.9
99167_Bayer Patient 1	30.6	94713_Donor 2 AD - B_adipose	66.4
97482_Patient-08ut_uterus	4.6	94714_Donor 2 AD - C_adipose	57.4
97483_Patient-08pl_placenta	3.8	94742_Donor 3 U - A_Mesenchymal	36.1
		Stem Cells
97486_Patient-09sk_skeletal	0.3	94743_Donor 3 U - B_Mesenchymal	62.4
muscle		Stem Cells
97487_Patient-09ut_uterus	8.3	94730_Donor 3 AM - A_adipose	34.9
97488_Patient-09pl_placenta	3.4	94731_Donor 3 AM - B_adipose	17.2
97492_Patient-10ut_uterus	7.5	94732_Donor 3 AM - C_adipose	22.4
97493_Patient-10pl_placenta	5.1	94733_Donor 3 AD - A_adipose	100.0
97495_Patient-11go_adipose	6.4	94734_Donor 3 AD - B_adipose	32.3
97496_Patient-11sk_skeletal	1.3	94735_Donor 3 AD - C_adipose	66.9
muscle
97497_Patient-11ut_uterus	11.6	77138_Liver_HepG2untreated	31.4
97498_Patient-11pl_placenta	3.9	73556_Heart_Cardiac stromal cells	3.6
		(primary)
97500_Patient-12go_adipose	8.5	81735_Small Intestine	6.4
97501_Patient-12sk_skeletal	2.7	72409_Kidney_Proximal Convoluted	3.8
muscle		Tubule
97502_Patient-12ut_uterus	8.7	82685_Small intestine_Duodenum	1.9
97503_Patient-12pl_placenta	3.1	90650_Adrenal_Adrenocortical	1.4
		adenoma
94721_Donor 2 U -	40.1	72410_Kidney_HRCE	14.9
A_Mesenchymal Stem Cells
94722_Donor 2 U -	23.7	72411_Kidney_HRE	11.1
B_Mesenchymal Stem Cells
94723_Donor 2 U -	52.5	73139_Uterus_Uterine smooth	17.4
C_Mesenchymal Stem Cells		muscle cells

[1197]

TABLE AUJ
Panel 5D
	Rel.	Rel.		Rel.	Rel.
	Exp. (%)	Exp. (%)		Exp. (%)	Exp. (%)
	Ag378,	Ag4075,		Ag3788,	Ag4075,
	Run	Run		Run	Run
Tissue Name	170222681	172167823	Tissue Name	170222681	172167823
97457_Patient-02go_adipose	8.2	11.0	94709_Donor 2 AM -	44.1	53.2
			A_adipose
97476_Patient-07sk_skeletal	2.1	2.8	94710_Donor 2 AM -	31.2	28.3
muscle			B_adipose
97477_Patient-07ut_uterus	3.5	7.1	94711_Donor 2 AM -	29.3	30.8
			C_adipose
97478_Patient-07pl_placenta	5.1	5.8	94712_Donor 2 AD -	77.4	81.8
			A_adipose
97481_Patient-08sk_skeletal	4.2	3.9	94713_Donor 2 AD -	100.0	100.0
muscle			B_adipose
97482_Patient-08ut_uterus	5.7	8.7	94714_Donor 2 AD -	68.8	84.1
			C_adipose
97483_Patient-08pl_placenta	7.5	7.2	94742_Donor 3 U -	55.1	66.9
			A_Mesenchymal Stem Cells
97486_Patient-09sk_skeletal	0.9	1.2	94743_Donor 3 U -	62.9	70.7
muscle			B_Mesenchymal Stem Cells
97487_Patient-09ut_uterus	8.5	11.0	94730_Donor 3 AM -	41.5	46.7
			A_adipose
97488_Patient-09pl_placenta	4.9	4.2	94731_Donor 3 AM -	29.7	29.5
			B_adipose
97492_Patient-10ut_uterus	5.7	5.8	94732_Donor 3 AM -	25.7	36.6
			C_adipose
97493_Patient-10pl_placenta	6.3	7.0	94733_Donor 3 AD -	97.3	92.7
			A_adipose
97495_Patient-11go_adipose	7.3	8.8	94734_Donor 3 AD -	58.6	80.7
			B_adipose
97496_Patient-11sk_skeletal	1.7	1.3	94735_Donor 3 AD -	69.3	83.5
muscle			C_adipose
97497_Patient-11ut_uterus	12.9	15.7	77138_Liver_HepG2untreated	72.7	80.7
97498_Patient-11pl_placenta	4.7	6.8	73556_Heart_Cardiac stromal	2.6	4.7
			cells (primary)
97500_Patient-12go_adipose	9.5	12.6	81735_Small Intestine	7.6	8.9
97501_Patient-12sk_skeletal	2.7	2.4	72409_Kidney_Proximal	4.6	4.3
muscle			Convoluted Tubule
97502_Patient-12ut_uterus	9.3	10.7	82685_Small	1.9	2.0
			intestine_Duodenum
97503_Patient-12pl_placenta	3.0	3.1	90650_Adrenal_Adrenocortical	1.4	1.1
			adenoma
94721_Donor 2 U -	50.3	52.9	72410_Kidney_HRCE	21.9	21.5
A_Mesenchymal Stem
Cells
94722_Donor 2 U -	45.4	47.3	72411_Kidney_HRE	15.7	0.0
B_Mesenchymal Stem
Cells
94723_Donor 2 U -	52.1	45.4	73139_Uterus_Uterine	23.7	28.3
C_Mesenchymal Stem			smooth muscle cells
Cells

[1198]

TABLE AUK
general oncology screening panel_v_2.4
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag4075,		Ag4075,
	Run		Run
Tissue Name	259745203	Tissue Nme	259745203
Colon cancer 1	50.7	Bladder cancer NAT 2	0.1
Colon cancer NAT 1	13.5	Bladder cancer NAT 3	0.0
Colon cancer 2	47.0	Bladder cancer NAT 4	0.1
Colon cancer NAT 2	24.3	Prostate adenocarcinoma 1	33.9
Colon cancer 3	95.9	Prostate adenocarcinoma 2	3.6
Colon cancer NAT 3	16.2	Prostate adenocarcinoma 3	26.4
Colon malignant cancer 4	55.9	Prostate adenocarcinoma 4	100.0
Colon normal adjacent tissue 4	6.2	Prostate cancer NAT 5	6.8
Lung cancer 1	11.4	Prostate adenocarcinoma 6	11.2
Lung NAT 1	0.6	Prostate adenocarcinoma 7	8.0
Lung cancer 2	12.9	Prostate adenocarcinoma 8	2.6
Lung NAT 2	1.0	Prostate adenocarcinoma 9	38.2
Squamous cell carcinoma 3	62.0	Prostate cancer NAT 10	0.6
Lung NAT 3	1.1	Kidney cancer 1	7.9
metastatic melanoma 1	20.2	KidneyNAT 1	2.9
Melanoma 2	3.1	Kidney cancer 2	28.1
Melanoma 3	1.7	Kidney NAT 2	8.5
metastatic melanoma 4	57.0	Kidney cancer 3	13.9
metastatic melanoma 5	25.3	Kidney NAT 3	2.1
Bladder cancer 1	0.2	Kidney cancer 4	9.6
Bladder cancer NAT 1	0.0	Kidney NAT 4	11.2
Bladder cancer 2	11.7

[1199] AI_comprehensive panel_v1.0 Summary: Ag4075 Highest expression is seen in an osteoarthritic bone sample (CT=27.31). This gene is expressed at moderate to low levels in many samples on this panel. Please see Panel 4.1 for discussion of this gene in inflammation.

[1200] CNS_neurodegeneration_v1.0 Summary: Ag4075 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 1.4 for discussion of this gene in the central nervous system.

[1201] General_screen_panel_v1.4 Summary: Ag4075 Two experiments with the same probe and primer set produce results that are in excellent agreement. Highest expression is seen in a colon cancer cell line (CTs=21-22). Overall, expression of this gene appears to be highly associated with cancer cell line samples, with high levels oof expression in brain, colon, gastric, lung, breast, ovarian, and melanoma cancer cell lines. This expression profile suggests a role for this gene product in cell survivaland proliferation. This gene encodes a protein with homology to Neutral amino acid transporter 2. L type amino acid transporter 1 (LAT1) has been implicated in tumor growth and may play an important role in supplying nutrition to cells for cell proliferation (Ohkame, J Surg Oncol 2001 Dec;78(4):265-71; discussion 271-2). Thus, modulation of this gene product may be useful in the treatment of cancer.

[1202] 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.

[1203] 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.

[1204] In addition, this gene is expressed at much higher levels in fetal lung and liver tissue (CTs=26-27) when compared to expression in the adult counterparts (CTs=31-33). Thus, expression of this gene may be used to differentiate between the fetal and adult sources of these tissues.

[1205] General_screen_panel_v1.5 Summary: Ag4075 Highest expression is seen in a colon cancer cell line (CT=20), with expression in this panel in strong agreement with Panel 1.4. Please see that panel for discussion of this gene in disease.

[1206] Panel 3D Summary: Ag4075 Expression of this gene is widespread on this panel, with highest expression in a lung cancer cell line (CT=26). The widespread expression on this panel is in agreement with expression in Panels 1.4 and 1.5 where expression of this gene is highly associated with cancer cell line samples. Please see Panel 1.4 for discussion of this gene in oncology.

[1207] Panel 4.1D Summary: Ag4075 Highest expression of this gene is seen in a sample derived from the Ramos B cell line treated with ionomycin (CT=27.3). In addition, this gene appears to be more highly expressed in activated T cells than in resting T cells. Thus, therapeutic regulation of the transcript or the protein encoded by the transcript could be important in immune modulation and in the treatment of T cell-mediated diseases such as asthma, arthritis, psoriasis, IBD, and lupus. In addition, 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_screen_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.

[1208] Panel 5 Islet Summary: Ag4075 Highest expression is seen in adipose (CT=27). In addition, this expression of this gene is widespread on this panel, with moderate to high levels in metabolic tissues, including skeletal muscle, adipose, pancreatic islet cells and placenta. This gene codes for neutral amino acid transporter B(0)[ATB(0)]. ATB(0) transports the gluconeogenic amino acids 1-alanine and 1-glutamine into cells. Excess neutral amino acid transport and a resultant increase in gluconeogenesis and triglyceride synthesis may impair beta cell function in obesity and Type 2 diabetes. Pharmacologic inhibition of ATB(0) encoded by this gene may prevent or treat the symptoms of obesity-related Type 2 diabetes.

[1209] Panel 5D Summary: Ag4075 Expression on this panel agrees with Panel 5I. Highest expression is seen in adipose in two replicate experiments (CTs=28). Please see Panel 5I and 1.4 for further discussion of utility of this gene in metabolic disease.

[1210] General oncology screening panel_v—2.4 Summary: Ag4975 Highest expression of this gene is seen in prostate cancer (CT=27). Prominent expression is also seen in melanoma and squamous cell carcinoma derived samples. In addition, this gene appears to be overexpressed in colon, lung, prostate cancer when compared to expression in the normal adjacent tissue. Thus, expression of this gene could be used as a marker to detect the presence of colon, lung and prostate cancer. Furthermore, therapeutic modulation of the expression or function of this gene may be effective in the treatment of colon, prostate, melanoma and lung cancer.

Example D: Identification of Single Nucleotide Polymorphisms in NOVX Nucleic Acid Sequences

[1211] 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.

[1212] 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.

[1213] 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 CuraTool™ program SeqExtend or by identifying SeqCalling fragments mapping to the appropriate regions of the genomic clones analyzed.

[1214] The regions defined by the procedures described above were then manually integrated and corrected for apparent inconsistencies that may have arisen, for example, from miscalled bases in the original fragments or from discrepancies between predicted exon junctions, EST locations and regions of sequence similarity, to derive the final sequence disclosed herein. When necessary, the process to identify and analyze SeqCalling assemblies and genomic clones was reiterated to derive the full length sequence (Alderborn et al., Determination of Single Nucleotide Polymorphisms by Real-time Pyrophosphate DNA Sequencing. Genome Research. 10 (8) 1249-1265, 2000).

[1215] 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.

[1216] NOV1a SNP Data:

[1217] NOV1a has one SNP variant, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs: 1 and 2, respectively. The nucleotide sequence of the NOVIa variant differs as shown in Table SNP1.

	TABLE SNP1
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13375555	4319	C	T	1440	Pro	Leu

[1218] NOV2b SNP Data:

[1219] NOV2b has six SNP variants, whose variant positions for its nucleotide and amino acid sequences are numbered according to SEQ ID NOs: 17 and 18, respectively. The nucleotide sequence of the NOV2b variant differs as shown in Table SNP2.

	TABLE SNP2
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
12252060	100	A	T	34	Ile	Phe
13380837	204	A	C	68	Thr	Thr
13380838	209	G	A	70	Gly	Asp
13380839	254	A	G	85	Gln	Arg
13380843	605	C	T	202	Ala	Val
13380844	614	C	T	205	Ala	Val

[1220] NOV3b SNP Data:

[1221] NOV3b has seven SNP variants, whose variant positions for its nucleotide and amino acid sequences are numbered according to SEQ ID NOs: 21 and 22, respectively. The nucleotide sequence of the NOV3b variant differs as shown in Table SNP3.

	TABLE SNP3
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13375856	338	G	A	0
13380855	397	T	G	0
13380857	1134	T	C	243	Val	Ala
13375853	1362	G	A	319	Arg	His
13380859	1376	A	G	324	Thr	Ala
13380860	1426	C	T	340	Cys	Cys
13380861	1496	C	T	0

[1222] NOV4b SNP Data:

[1223] NOV4b has eleven SNP variants, whose variant positions for its nucleotide and amino acid sequences are numbered according to SEQ ID NOs: 27 and 28, respectively. The nucleotide sequence of the NOV4b variant differs as shown in Table SNP4.

	TABLE SNP4
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13380847	73	C	C	12	Arg	Pro
13380848	116	G	A	26	Arg	Arg
13380849	117	A	T	27	Ile	Phe
13380862	200	G	T	54	Lys	Asn
13380863	222	C	T	62	Glu	End
13380864	243	C	T	69	Glu	End
13380850	338	C	T	100	Ile	Ile
13380851	438	C	T	134	Ala	Ser
13380865	779	A	T	247	Pro	Pro
13380852	1023	C	G	329	Pro	Ala
13380853	1494	C	T	0

[1224] NOV6a SNP Data:

[1225] NOV6a has two SNP variants, whose variant positions for its nucleotide and amino acid sequences are numbered according to SEQ ID NOs: 33 and 34, respectively. The nucleotide sequence of the NOV6a variant differs as shown in Table SNP5.

	TABLE SNP5
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13380868	1646	T	C	539	Val	Ala
13380869	2992	T	C	988	Cys	Arg

[1226] NOV11a SNP Data:

[1227] NOV11a has one SNP variant, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs: 47 and 48, respectively. The nucleotide sequence of the NOV11a variant differs as shown in Table SNP6.

	TABLE SNP6
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13380962	41	G	T	0

[1228] NOV12a SNP Data:

[1229] NOV12a has three SNP variants, whose variant positions for its nucleotide and amino acid sequences are numbered according to SEQ ID NOs: 63 and 64, respectively. The nucleotide sequence of the NOV 12a variant differs as shown in Table SNP7.

	TABLE SNF7
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13380902	594	C	T	193	Ser	Ser
13380901	1392	A	C	0
13380900	1425	C	T	0

[1230] NOV13a SNP Data:

[1231] NOV13a has one SNP variant, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs: 65 and 66, respectively. The nucleotide sequence of the NOV13a variant differs as shown in Table SNP8.

	TABLE SNP8
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13380964	204	C	T	68	Leu	Leu

[1232] NOV14a SNP Data:

[1233] NOV14a has two SNP variants, whose variant positions for its nucleotide and amino acid sequences are numbered according to SEQ ID NOs: 73 and 74, respectively. The nucleotide sequence of the NOV14a variant differs as shown in Table SNP9.

	TABLE SNP9
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13380922	106	C	G	28	Pro	Pro
13380923	760	A	G	246	Pro	Pro

[1234] NOV15a SNP Data:

[1235] NOV15a has two SNP variants, whose variant positions for its nucleotide and amino acid sequences are numbered according to SEQ ID NOs: 77 and 78, respectively. The nucleotide sequence of the NOV1Sa variant differs as shown in Table SNP10.

	TABLE SNP10
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13380896	19	T	C	4	Phe	Leu
13380897	258	G	A	83	Pro	Pro

[1236] NOV20a SNP Data:

[1237] NOV20a has seven SNP variants, whose variant positions for its nucleotide and amino acid sequences are numbered according to SEQ ID NOs: 107 and 108, respectively. The nucleotide sequence of the NOV20a variant differs as shown in Table SNP11.

	TABLE SNP11
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13380969	155	G	A	0
13380970	448	A	G	79	His	Arg
13380971	475	G	C	88	Cys	Ser
13380972	780	A	G	190	Arg	Gly
13380974	890	A	G	226	Arg	Arg
13380975	1798	A	G	0
13380976	2564	A	G	0

[1238] V26a SNP Data: V26a has one SNP variant, whose variant positions for its nucleotide and amino ces is numbered according to SEQ ID NOs: 119 and 120, respectively. The sequence of the NOV26a variant differs as shown in Table SNP12.

	TABLE SNP12
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13377803	98	C	A	25	Met	Ile

[1239] V27a SNP Data:

[1240] NOV27a has two SNP variants, whose variant positions for its nucleotide and sequences are numbered according to SEQ ID NOs: 121 and 122, respectively. tide sequence of the NOV27a variant differs as shown in Table SNP13.

	TABLE SNP13
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13380980	186	A	G	22	Thr	Ala
13380979	292	C	T	57	Thr	Ile

[1241] NOV28a SNP Data:

[1242] NOV28a has two SNP variants, whose variant positions for its nucleotide and amino acid sequences are numbered according to SEQ ID NOs: 123 and 124, respectively. The nucleotide sequence of the NOV28a variant differs as shown in Table SNP14.

	TABLE SNP14
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13380981	2192	G	A	721	Arg	Lys
13380982	2283	C	T	751	Phe	Phe

[1243] NOV29a SNP Data:

[1244] NOV29a has one SNP variant, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs: 127 and 128, respectively. The nucleotide sequence of the NOV29a variant differs as shown in Table SNP15.

	TABLE SNP15
	Nucleotides	Amino Acids
Variants	Position	Initial	Modified	Position	Initial	Modified
13380985	46	T	C	0

[1245] NOV31a SNP Data:

[1246] NOV31a has one SNP variant, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs: 133 and 134, respectively. The nucleotide sequence of the NOV31a variant differs as shown in Table SNP16.

	TABLE SNP16
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13380984	1232	G	A	335	Gly	Ser

[1247] NOV34a SNP Data:

[1248] NOV34a has two SNP variants, whose variant positions for its nucleotide and amino acid sequences are numbered according to SEQ ID NOs: 141 and 142, respectively. The nucleotide sequence of the NOV34a variant differs as shown in Table SNP17.

	TABLE SNP17
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13380987	1145	G	C	362	Arg	Thr
13380988	1749	A	T	0

[1249] NOV35a SNP Data:

[1250] NOV35a has one SNP variant, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs: 143 and 144, respectively. The nucleotide sequence of the NOV35a variant differs as shown in Table SNP18.

	TABLE SNP18
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13380995	85	C	T	122	Thr	Ile

[1251] NOV36a SNP Data:

[1252] NOV36a has three SNP variants, whose variant positions for its nucleotide and amino acid sequences are numbered according to SEQ ID NOs: 153 and 154, respectively. The nucleotide sequence of the NOV36a variant differs as shown in Table SNP19.

	TABLE SNP19
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13380998	411	G	A	122	Ser	Asn
13381013	492	T	C	149	Leu	Pro
13380999	686	T	C	214	Cys	Arg

[1253] NOV37a SNP Data:

[1254] NOV37a has one SNP variant, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs: 155 and 156, respectively. The nucleotide sequence of the NOV37a variant differs as shown in Table SNP20.

	TABLE SNP20
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13381009	2077	C	G	0

[1255] NOV38a SNP Data:

[1256] NOV38a has one SNP variant, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs: 157 and 158, respectively. The nucleotide sequence of the NOV38a variant differs as shown in Table SNP21.

	TABLE SNP21
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13378369	994	C	T	330	Ser	Leu

[1257] NOV40a SNP Data:

[1258] NOV40a has one SNP variant, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs: 167 and 168, respectively. The nucleotide sequence of the NOV40a variant differs as shown in Table SNP22.

	TABLE SNP22
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13381011	32	A	G	0

[1259] NOV41a SNP Data:

[1260] NOV41a has two SNP variants, whose variant positions for its nucleotide and amino acid sequences are numbered according to SEQ ID NOs: 173 and 174, respectively. The nucleotide sequence of the NOV41a variant differs as shown in Table SNP23.

	TABLE SNP23
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13380997	247	A	G	55	Asn	Asp
13380996	417	A	G	111	Lys	Lys

[1261] NOV43a SNP Data:

[1262] NOV43a has eight SNP variants, whose variant positions for its nucleotide and amino acid sequences are numbered according to SEQ ID NOs: 181 and 182, respectively. The nucleotide sequence of the NOV43a variant differs as shown in Table SNP24.

	TABLE SNP24
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13381140	184	G	A	61	Asp	Asn
13381141	337	T	C	112	Phe	Leu
13381158	729	G	T	242	Met	Ile
13381157	748	A	G	249	Ser	Gly
13381156	934	T	C	311	Phe	Leu
13381142	1916	A	G	0
13381143	2123	T	A	0
13381148	2260	G	C	0

[1263] NOV44a SNP Data:

[1264] NOV44a has one SNP variant, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs: 183 and 184, respectively. The nucleotide sequence of the NOV44a variant differs as shown in Table SNP25.

	TABLE SNP25
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13381168	1096	C	T	0

[1265] NOV45a SNP Data:

[1266] NOV45a has two SNP variants, whose variant positions for its nucleotide and amino acid sequences are numbered according to SEQ ID NOs: 185 and 186, respectively. The nucleotide sequence of the NOV45a variant differs as shown in Table SNP26.

	TABLE SNP26
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13381163	1269	T	C	399	Cys	Arg
13381162	1418	C	T	0

[1267] NOV46a SNP Data:

[1268] NOV46a has one SNP variant, whose variant positions for its nucleotide and amino acid sequences is numbered according to SEQ ID NOs: 187 and 188, respectively. The nucleotide sequence of the NOV46a variant differs as shown in Table SNP27.

	TABLE SNP27
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13381020	820	T	C	267	Phe	Phe

[1269] NOV48b SNP Data:

[1270] NOV48b has five SNP variants, whose variant positions for its nucleotide and amino acid sequences are numbered according to SEQ ID NOs: 193 and 194, respectively. The nucleotide sequence of the NOV48b variant differs as shown in Table SNP28.

	TABLE SNP28
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13375777	107	A	G	14	His	Arg
13376584	116	G	A	17	Ser	Asn
13381146	448	T	C	128	Cys	Arg
13378857	1282	G	A	406	Gly	Ser
13376583	1297	C	T	411	Pro	Ser

[1271] NOV49a SNP Data:

[1272] NOV49a has twenty-one SNP variants, whose variant positions for its nucleotide and amino acid sequences are numbered according to SEQ ID NOs: 195 and 196, repectively. The nucleotide sequence of the NOV49a variant differs as shown in Table SNP29.

	TABLE SNP29
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13379126	186	C	T	17	Ala	Val
13375663	212	C	G	26	Leu	Val
13375662	213	T	C	26	Leu	Pro
13379016	293	A	G	53	Ser	Gly
13378698	388	C	T	84	Phe	Phe
13381282	401	C	T	89	Gln	End
13381193	556	A	C	140	Thr	Thr
13381194	577	G	A	147	Gly	Gly
13381283	631	A	G	165	Lys	Lys
13378699	840	G	A	235	Ser	Asn
13378106	909	A	G	258	Asp	Gly
13381284	924	A	G	263	Lys	Arg
13377887	954	A	G	273	Glu	Gly
13381285	967	C	T	277	Gly	Gly
13381286	1009	A	G	291	Thr	Thr
13377889	1083	A	G	316	Gln	Arg
13381287	1107	A	C	324	Glu	Gly
13377890	1113	T	C	326	Val	Ala
13377891	1137	A	C	334	Gln	Pro
13381288	1196	C	G	0
13381289	1202	A	G	0

[1273] NOV50b SNP Data:

[1274] NOV50b has three SNP variants, whose variant positions for its nucleotide and amino acid sequences are numbered according to SEQ ID NOs: 219 and 220, respectively. The nucleotide sequence of the NOV50b variant differs as shown in Table SNP30.

	TABLE SNP23
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13381192	216	G	A	48	Glu	Glu
13381177	602	G	T	177	Arg	Leu
13381190	698	C	T	0

[1275] NOV52b SNP Data:

[1276] NOV52b has eight SNP variants, whose variant positions for its nucleotide and amino acid sequences are numbered according to SEQ ID NOs: 229 and 230, respectively. The nucleotide sequence of the NOV52b variant differs as shown in Table SNP31.

	TABLE SNP31
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13381176	215	A	G	43	Glu	Glu
13376180	320	C	T	78	Tyr	Tyr
13376179	397	A	G	104	Gln	Arg
13381171	519	T	C	145	Ser	Pro
13381174	629	C	T	181	Ile	Ile
13381173	1173	C	A	363	Gln	Lys
13381172	1174	A	C	363	Gln	Pro
13381169	1402	A	G	0

[1277] NOV53c SNP Data:

[1278] NOV53c has two SNP variants, whose variant positions for its nucleotide and amino acid sequences are numbered according to SEQ ID NOs: 237 and 238, respectively. The nucleotide sequence of the NOV53c variant differs as shown in Table SNP32.

	TABLE SNP32
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13380578	424	C	T	136	Asp	Asp
13380577	869	A	G	285	Thr	Ala

[1279] NOV55a SNP Data:

[1280] NOV55a has thirteen SNP variants, whose variant positions for its nucleotide and amino acid sequences are numbered according to SEQ ID NOs: 245 and 246, respectively. The nucleotide sequence of the NOV55a variant differs as shown in Table SNP33.

TABLE SNP33.
	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
13375283	272	C	T	0
13375284	281	T	C	0
13377920	1226	T	C	203	Ser	Pro
13377921	1447	C	T	276	Tyr	Tyr
13377922	1765	C	T	382	Gly	Gly
13377907	2021	A	G	468	Thr	Ala
13377908	2074	T	C	485	Tyr	Tyr
13375287	2153	G	C	512	Val	Leu
13375288	2157	C	T	513	Pro	Leu
13375289	2160	C	T	514	Thr	lie
13375290	2329	G	A	0
13377903	2417	A	G	0
13377904	2559	C	T	0

Example E: Potential Role(s) of CG96736-01 in Obesity and/or Diabetes

[1281] The NOV55a gene (CG96736-01) is a Na+-dependent neutral amino acid transporter that exhibits high affinity electroneutral uptake of neutral amino acids such as L-alanine, L-serine, L-threonine, L-cysteine and L-glutamine. This transporter prefers neutral amino acids without bulky or branched side chains. It is localized to the plasma membrane and has eight putative transmembrane segments. It appears to be a Type IIIa membrane protein with an N-terminal cytoplasmic tail and a C-terminal extracellular segment. In this respect, the expression patter and its function in nutral amino acid uptake is an indication of a role for NOV55a in obesity and/or diabetes.

[1282] Obesity and Diabetes are major public health concerns in the developed and developing world. It is estimated that over half of the adult US population is overweight with a body mass index (BMI) greater than the upper limit of normal (25) where the BMI is defined as the weight (Kg)/[height (m)]2. A common consequence of being overweight is hyperlipidemia and the development of insulin resistance. This is followed by the development of hyperglycemia—a hallmark of Type II diabetes. Left untreated, the hyperglycemia leads to microvascular disease and end organ damage that includes retinopathy, renal disease, cardiac disease, peripheral neuropathy and peripheral vascular compromise. Currently, over 16 million adults in the US are affected and the condition has now become rampant among school-age children as a consequence of the epidemic of obesity in that age group.

[1283] Several cellular, animal and clinical studies were performed to elucidate the genetic contribution to the etiology and pathogenesis of these conditions in a variety of physiologic, pharmacologic or native states. These studies utilized 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.

[1284] 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.

[1285] 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.

[1286] In an important aspect, the present invention provides a method of identifying a candidate therapeutic agent for treating a disease, pathology, or an abnormal state or condition using a target entity having a specific association with the disease. This method includes:

[1287] (a) identification of a target biopolymer associated with the disease, pathology, or abnormal state or condition;

[1288] (b) contacting the biopolymer with at least one chemical compound; and

[1289] (c) identifying a compound that binds to the biopolymer as a candidate therapeutic agent.

[1290] In important embodiments of this method, the chemical compound is a member of a combinatorial library of compounds; the contacting in step (b) is conducted on one or more replicate samples of the biopolymer; and the replicate sample is contacted with at least one member of the combinatorial library. In additional embodiments of this method, the biopolymer is included within a cell and is functionally expressed therein. In still a further advantageous embodiment, the binding of the compound modulates the function of the biopolymer, and it is the modulation that provides the identification that the compound is a potential therapeutic agent. In yet further significant embodiments of this method, the target biopolymer is a polypeptide.

[1291] In a second aspect of the invention, a method for identifying a pharmaceutical agent for treating a disease, pathology, or an abnormal state or condition is provided. The second method includes the steps of:

[1292] (a) identifying a candidate therapeutic agent for treating said disease, pathology, or abnormal state or condition by the method described in the preceding paragraph;

[1293] (b) contacting a biological sample associated with the disease, pathology, or abnormal state or condition with the candidate therapeutic agent;

[1294] (c) determining whether the candidate induces an effect on the biological sample associated with a therapeutic response therein; and

[1295] (d) identifying a candidate exerting such an effect as a pharmaceutical agent.

[1296] In significant embodiments of the second method, the biological sample includes a cell, a tissue or organ, or is a nonhuman mammal.

[1297] A gene fragment of the mouse Neutral Amino Acid Transporter B was initially found to be up-regulated by 6 fold in the adipose tissue of obese mice (AKR) relative to non-obese mice (C57BL/6J) using CuraGen's GeneCalling™ method of differential gene expression. Two differentially expressed mouse gene fragments migrating, at approximately 138 and 347 nucleotides in length (Tables MOU-3A and MOU-3B for NOV55c (SEQ ID NO: 438), and Tables MOU-3C and MOU-3D for NOV55d (SEQ ID NO: 439) respectively—vertical line) were definitively identified as a component of the Mouse Neutral Amino Acid Transporter B 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 electropherogramatic peaks corresponding to the gene fragment of the mouse Neutral Amino Acid Transporter B are ablated when a gene-specific primer competes with primers in the linker-adaptors during the PCR amplification. The peaks at 138 nt length are ablated in the sample from both the obese and non-obese mice.

[1298] The direct sequences of the 138.4 and 346.7 nucleotide-long gene fragments and the gene-specific primers used for competitive PCR are indicated on the cDNA sequence of the Mouse Neutral Amino Acid Transporter B are shown below in bold. The gene-specific primers at the 5′ and 3′ ends of the fragment are in italics.

[1299] Competitive PCR Primer for the Mouse Neutral Amino Acid Transporter B (peak at 138.4).

TABLE MOU-1
NOV55c Gene Sequence
(fragment from 564 to 700 in bold. band size: 137)
(SEQ ID NO:438)
83	CCAGAGAGGA CCAGAGTGCG AAAGCAGGTG GTTGCTGCGG TTCCCGTGAC CGGGTGCGCC	143
	GCTGCATTCG CGCCAACCTG CTGGTGCTGC TCACGGTGGC TGCGGTGGTG GCTGGCGTGG	203
	GGCTGGGGCT GGGGGTCTCG GCGGCGGGCG GTGCTGACGC CCTGGGTCCC GCGCGCTTGA	263
	CCGCTTTCGC CTTCCCGGGA GAGCTGCTGC TGCGTCTGCT GAAGATGATC ATCCTGCCCC	323
	TCGTGGTGTG CAGCCTGATC GGAGGTGCAG CCAGCTTGGA CCCTAGCGCG CTCGGTCGTG	383
	TGGGCGCCTG GGCGCTGCTC TTTTTCCTGG TCACCACACT GCTCGCGTCG GCGCTCGGCG	443
	TGGGTTTGGC CCTGGCGCTG AAGCCCGGCG CCGCCGTTAC CGCCATCACC TCCATCAACG	503
	ACTCTGTTGT AGACCCCTGT GCCCGCAGTG CACCAACCAA AGAGGTGCTG GATTCCTTTC	563
	TAGATCTCGT CAGGAATATT TTCCCCTCCA ATCTGGTGTC TGCTGCCTTC CGCTCTTTTG	623
	CTACCTCATA TGAACCCAAA GACAACTCAT GTAAAATACC GCAATCCTGT ATCCAGCGGG	683
	AGATCAATTC AACCATGGTC CAGCTTCTCT GTGAGGTGGA GCGAATGAAC ATCCTGGGCC	743
	TGGTGGTCTT CGCTATCGTC TTTGGTGTGG CTCTGCGGAA GCTGGGGCCC GAGGGTGAGC	803
	TGCTCATTCG TTTCTTCAAC TCCTTCAATG ATGCCACCAT GGTCCTGGTC TCCTGGATTA	863
	TGTGGTACGC ACCCGTTGGA ATCCTGTTCC TGGTGGCCAG CAAGATTGTG GAGATGAAAG	923
	ACGTCCGCCA GCTCTTCATC AGCCTCGGCA AATACATTCT GTGCTGCCTG CTGGGCCACG	983
	CCATCCACGG GCTCCTGGTT CTGCCTCTCA TCTACTTCCT CTTCACCCGC AAAAATCCCT	1043
	ATCGATTCCT GTGGGGCATC ATGACACCCC TGGCCACTGC TTTCGGGACC TCTTCTAGCT	1103
	CTGCCACCTT GCCTCTGATG ATGAAGTGTG TAGAGGAGAA GAATGGTGTG GCCAAACACA	1163
	TCAGCCGGTT CATCCTAC
	(gene length is 1668, only region from 83 to 1180 shown)

[1300] Competitive PCR Primer for the Mouse Neutral Amino Acid Transporter B (peak at 346.7). The gene-specific primers at the 5′ and 3′ ends of the fragment are in italics.

TABLE MOU-2
NOV55d Gene Sequence
(fragment from 1 to 347 in italics, band size: 347)
(SEQ ID NO:439)
GGAPCCCTGC CGCACCGACA CTGGATGCTG TGGCTGTGAC CCTGGGGAAG AGAAGAGCGG 61
AGATGGCAGA ATCATGGGGG CGGGGCCTCC TGCCACAGCC CCTGGCACTC ACAGGATGGT 121
GATGATCTTC ACGAAGTCCA GCGACACCCC GTTTAGTTGT GCGATGAACA CTGCCGCCAC 181
ACACTGGAAC AGCGCCGCCC CGTCCATGTT GACCGTCGCG CCGATGGGTA GGATCAACCG 241
GCTGATGTGT TTGGCCACAC CATTCTTCTC CTCTACACAC TTCATCATCA GAGGCAAGGT 301
GGCAGAGCTA GAAGAGGTCC CGAAAGCAGT GGCCAGGGGT GTCATGA
(gene length is 347, only region from 1 to 347 shown)

[1301] Nucleic acid and amino acid sequences for NOV55a and NOV55b are disclosed in Table 55a, SNPs for NOV55a and NOV55b are disclosed in Table SNP33 and quantitative expression of these genes is shown in Tables AUA-AUK in Example D.

[1302] Tables MOU-3A and MOU-3B show differentially expressed mouse neutral amino acid transporter B gene fragment, NOV55c, and Tables MOU-3C and MOU-3D shows differentially expressed mouse neutral amino acid transporter B gene fragment, NOV55d.

OTHER EMBODIMENTS

[1303] 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 124.

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 124.

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 124.

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 124.

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 l, 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 124 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 124.

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 124.

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 124.

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 124.

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 124, 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 124.

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 124.

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.