Therapeutic polypeptides, nucleic acids encoding same, and methods of use

Abstract

Disclosed herein are nucleic acid sequences that encode novel polypeptides. Also disclosed are polypeptides encoded by these nucleic acid sequences, and antibodies that immunospecifically bind to the polypeptide, as well as derivatives, variants, mutants, or fragments of the novel polypeptide, polynucleotide, or antibody specific to the polypeptide. Vectors, host cells, antibodies and recombinant methods for producing the polypeptides and polynucleotides, as well as methods for using same are also included. 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, and the nucleic acids encoding them, having 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 OF THE INVENTION

[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] Antibodies are multichain proteins that bind specifically to a given antigen, and bind poorly, or not at all, to substances deemed not to be cognate antigens. Antibodies are comprised of two short chains termed light chains and two long chains termed heavy chains. These chains are constituted of immunoglobulin domains, of which generally there are two classes: one variable domain per chain, one constant domain in light chains, and three or more constant domains in heavy chains. The antigen-specific portion of the immunoglobulin molecules resides in the variable domains; the variable domains of one light chain and one heavy chain associate with each other to generate the antigen-binding moiety. Antibodies that bind immunospecifically to a cognate or target antigen bind with high affinities. Accordingly, they are useful in assaying specifically for the presence of the antigen in a sample. In addition, they have the potential of inactivating the activity of the antigen.

[0008] Therefore there is a need to assay for the level of a protein effector of interest in a biological sample from such a subject, and to compare this level with that characteristic of a nonpathological condition. In particular, there is a need for such an assay based on the use of an antibody that binds immunospecifically to the antigen. There further is a need to inhibit the activity of the protein effector in cases where a pathological condition arises from elevated or excessive levels of the effector based on the use of an antibody that binds immunospecifically to the effector. Thus, there is a need for the antibody as a product of manufacture. There further is a need for a method of treatment of a pathological condition brought on by an elevated or excessive level of the protein effector of interest based on administering the antibody to the subject.

SUMMARY OF THE INVENTION

[0009] The invention is based in part upon the discovery of isolated polypeptides including amino acid sequences selected from mature forms of the amino acid sequences selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 77. The novel nucleic acids and polypeptides are referred to herein as NOV1a, NOV1b, NOV2a, NOV2b, NOV2c, NOV2d, NOV3a, NOV3b, NOV3c, NOV3d, NOV3e, NOV3f, NOV3g, NOV3h, NOV3i, NOV3j, NOV3k, NOV3l, NOV3m, NOV3n, NOV3o, NOV3p, NOV3q, NOV4a, NOV4b, NOV4c, NOV5a, NOV5b, NOV6a, NOV6b, NOV6c, NOV7a, NOV8a, NOV8b, NOV9a, NOV9b, NOV9c, NOV9d, NOV9e, NOV10a, NOV11a, NOV12a, NOV13a, NOV13b, NOV14a, NOV15a, NOV15b, NOV16a, NOV16b, NOV16c, NOV17a, NOV17b, NOV17c, NOV17d, NOV18a, NOV18b, NOV19a, NOV19b, NOV20a, NOV20b, NOV20c, NOV21a, NOV22a, NOV22b, NOV22c, NOV23a, NOV23b, NOV24a, NOV25a, NOV26a, NOV27a, NOV27b, NOV27c, NOV28a, NOV28b, NOV28c and NOV28d. These nucleic acids and polypeptides, as well as derivatives, homologs, analogs and fragments thereof, will hereinafter be collectively designated as “NOVX” nucleic acid or polypeptide sequences.

[0010] The invention also is based in part upon variants 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 77, 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. In another embodiment, the invention includes the amino acid sequences selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 77. In another embodiment, the invention also comprises variants of the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 77 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 involves fragments of any of the mature forms of the amino acid sequences selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 77, or any other amino acid sequence selected from this group. The invention also comprises fragments from these groups in which up to 15% of the residues are changed.

[0011] In another embodiment, the invention encompasses polypeptides that are naturally occurring allelic variants of the sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 77. These allelic variants include amino acid sequences that are the translations of nucleic acid sequences differing by a single nucleotide from nucleic acid sequences selected from the group consisting of SEQ ID NOS: 2n−1, wherein n is an integer between 1 and 77. The variant polypeptide where any amino acid changed in the chosen sequence is changed to provide a conservative substitution.

[0012] In another embodiment, the invention comprises a pharmaceutical composition involving a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 77 and a pharmaceutically acceptable carrier. In another embodiment, the invention involves a kit, including, in one or more containers, this pharmaceutical composition.

[0013] In another embodiment, the invention includes the use of a therapeutic in the manufacture of a medicament for treating a syndrome associated with a human disease, the disease being selected from a pathology associated with a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 77 wherein said therapeutic is the polypeptide selected from this group.

[0014] In another embodiment, the invention comprises a method for determining the presence or amount of a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 77 in a sample, the method involving providing the sample; introducing the sample to an antibody that binds immunospecifically to the polypeptide; and determining the presence or amount of antibody bound to the polypeptide, thereby determining the presence or amount of polypeptide in the sample.

[0015] In another embodiment, the invention includes a method for determining the presence of or predisposition to a disease associated with altered levels of a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 77 in a first mammalian subject, the method involving measuring the level of expression of the polypeptide in a sample from the first mammalian subject; and comparing the amount of the polypeptide in this sample to the amount of the polypeptide present in a control sample from a second mammalian subject known not to have, or not to be predisposed to, the disease, wherein an alteration in the expression level of the polypeptide in the first subject as compared to the control sample indicates the presence of or predisposition to the disease.

[0016] In another embodiment, the invention involves a method of identifying an agent that binds to a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 77, the method including introducing the polypeptide to the agent; and determining whether the agent binds to the polypeptide. The agent could be a cellular receptor or a downstream effector.

[0017] In another embodiment, the invention involves a method for identifying a potential therapeutic agent for use in treatment of a pathology, wherein the pathology is related to aberrant expression or aberrant physiological interactions of a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 77, the method including providing a cell expressing the polypeptide of the invention and having a property or function ascribable to the polypeptide; contacting the cell with a composition comprising a candidate substance; and determining whether the substance alters the property or function ascribable to the polypeptide; whereby, if an alteration observed in the presence of the substance is not observed when the cell is contacted with a composition devoid of the substance, the substance is identified as a potential therapeutic agent.

[0018] In another embodiment, the invention involves a method for screening for a modulator of activity or of latency or predisposition to a pathology associated with 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 77, the method including administering a test compound to a test animal at increased risk for a pathology associated with the polypeptide of the invention, wherein the test animal recombinantly expresses the polypeptide of the invention; measuring the activity of the polypeptide in the test animal after administering the test compound; and comparing the activity of the protein in the test animal with the activity of the polypeptide in a control animal not administered the polypeptide, wherein a change in the activity of the 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 polypeptide of the invention. The recombinant test animal could express a test protein transgene or express the transgene under the control of a promoter at an increased level relative to a wild-type test animal The promoter may or may not b the native gene promoter of the transgene.

[0019] In another embodiment, the invention involves a method for modulating the activity of a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 77, the method including introducing a cell sample expressing the polypeptide with a compound that binds to the polypeptide in an amount sufficient to modulate the activity of the polypeptide.

[0020] In another embodiment, the invention involves a method of treating or preventing a pathology associated with a polypeptide with an amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 77, the method including administering the polypeptide to a subject in which such treatment or prevention is desired in an amount sufficient to treat or prevent the pathology in the subject. The subject could be human.

[0021] In another embodiment, the invention involves a method of treating a pathological state in a mammal, the method including 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 having the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 77 or a biologically active fragment thereof.

[0022] In another embodiment, the invention involves an isolated nucleic acid molecule comprising a nucleic acid sequence encoding a polypeptide having an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 77; 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 77 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; the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 77; 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 77, 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; 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 77 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; and the complement of any of the nucleic acid molecules.

[0023] In another embodiment, the invention comprises an isolated nucleic acid molecule having a nucleic acid sequence encoding a polypeptide comprising an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 77, wherein the nucleic acid molecule comprises the nucleotide sequence of a naturally occurring allelic nucleic acid variant.

[0024] In another embodiment, the invention involves an isolated nucleic acid molecule including a nucleic acid sequence encoding a polypeptide having an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 77 that encodes a variant polypeptide, wherein the variant polypeptide has the polypeptide sequence of a naturally occurring polypeptide variant.

[0025] In another embodiment, the invention comprises an isolated nucleic acid molecule having a nucleic acid sequence encoding a polypeptide comprising an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 77, wherein the nucleic acid molecule differs by a single nucleotide from a nucleic acid sequence selected from the group consisting of SEQ ID NOS: 2n−1, wherein n is an integer between 1 and 77.

[0026] In another embodiment, the invention includes an isolated nucleic acid molecule having a nucleic acid sequence encoding a polypeptide including an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 77, wherein the nucleic acid molecule comprises a nucleotide sequence selected from the group consisting of the nucleotide sequence selected from the group consisting of SEQ ID NO:2n−1, wherein n is an integer between 1 and 77; 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 77 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; 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 77; and 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 77 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.

[0027] In another embodiment, the invention includes an isolated nucleic acid molecule having a nucleic acid sequence encoding a polypeptide including an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 77, wherein the 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 77, or a complement of the nucleotide sequence.

[0028] In another embodiment, the invention includes an isolated nucleic acid molecule having a nucleic acid sequence encoding a polypeptide including an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 77, wherein the nucleic acid molecule has a nucleotide sequence in which any nucleotide specified in the coding sequence of the chosen 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 in the chosen coding sequence are so changed, an isolated second polynucleotide that is a complement of the first polynucleotide, or a fragment of any of them.

[0029] In another embodiment, the invention includes a vector involving the nucleic acid molecule having a nucleic acid sequence encoding a polypeptide including an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 77. This vector can have a promoter operably linked to the nucleic acid molecule. This vector can be located within a cell.

[0030] In another embodiment, the invention involves a method for determining the presence or amount of a nucleic acid molecule having a nucleic acid sequence encoding a polypeptide including an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 77 in a sample, the method including 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 nucleic acid molecule, thereby determining the presence or amount of the nucleic acid molecule in the sample. The presence or amount of the nucleic acid molecule is used as a marker for cell or tissue type. The cell type can be cancerous.

[0031] In another embodiment, the invention involves a method for determining the presence of or predisposition for a disease associated with altered levels of a nucleic acid molecule having a nucleic acid sequence encoding a polypeptide including an amino acid sequence selected from the group consisting of a mature form of the amino acid sequence given SEQ ID NO:2n, wherein n is an integer between 1 and 77 in a first mammalian subject, the method including measuring the amount of the 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 the nucleic acid present in a control sample from a second mammalian subject known not to have or not be predisposed to, the disease; wherein an alteration in the level of the nucleic acid in the first subject as compared to the control sample indicates the presence of or predisposition to the disease.

[0032] The invention further provides an antibody that binds immunospecifically to a NOVX polypeptide. The NOVX antibody may be monoclonal, humanized, or a fully human antibody. Preferably, the antibody has a dissociation constant for the binding of the NOVX polypeptide to the antibody less than 1×10−9 M. More preferably, the NOVX antibody neutralizes the activity of the NOVX polypeptide.

[0033] In a further aspect, the invention provides for the use of a therapeutic in the manufacture of a medicament for treating a syndrome associated with a human disease, associated with a NOVX polypeptide. Preferably the therapeutic is a NOVX antibody.

[0034] In yet a further aspect, the invention provides a method of treating or preventing a NOVX-associated disorder, a method of treating a pathological state in a mammal, and a method of treating or preventing a pathology associated with a polypeptide by administering a NOVX antibody to a subject in an amount sufficient to treat or prevent the disorder.

[0035] 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 are not intended to be limiting.

[0036] Other features and advantages of the invention will be apparent from the following detailed description and claims.

DETAILED DESCRIPTION OF THE INVENTION

[0037] 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
NOV1a	CG102689-01	1	2	Von Ebner's gland
				protein precursor
NOV1b	CG102689-02	3	4	Von Ebner's gland
				protein precursor
NOV2a	CG103827-01	5	6	Fibulin-2
NOV2b	CG103827-02	7	8	Fibulin-2
NOV2c	CG103827-03	9	10	Fibulin-2
NOV2d	CG103827-04	11	12	Fibulin-2
NOV3a	CG105716-09	13	14	Cartilage oligomeric
				matrix protein
NOV3b	CG105716-05	15	16	Cartilage oligomeric
				matrix protein
NOV3c	CG105716-06	17	18	Cartilage oligomeric
				matrix protein
NOV3d	CG105716-04	19	20	Cartilage oligomeric
				matrix protein
NOV3e	CG105716-03	21	22	Cartilage oligomeric
				matrix protein
NOV3f	CG105716-02	23	24	Fibulin-2
NOV3g	CG105716-01	25	26	Germline oligomeric
				matrix protein
NOV3h	207569245	27	28	Cartilage oligomeric
				matrix protein
NOV3i	207569277	29	30	Cartilage oligomeric
				matrix protein
NOV3j	207569281	31	32	Cartilage oligomeric
				matrix protein
NOV3k	248644823	33	34	Cartilage oligomeric
				matrix protein
NOV3l	248644900	35	36	Cartilage oligomeric
				matrix protein
NOV3m	248576435	37	38	Cartilage oligomeric
				matrix protein
NOV3n	310681505	39	40	Cartilage oligomeric
				matrix protein
NOV3o	CG105716-07	41	42	Cartilage oligomeric
				matrix protein
NOV3p	CG105716-08	43	44	Cartilage oligomeric
				matrix protein
NOV3q	CG105716-10	45	46	Cartilage oligomeric
				matrix protein
NOV4a	CG153910-01	47	48	Secreted protein
				CGI-100
NOV4b	CG153910-02	49	50	Secreted protein
				CGI-100
NOV4c	CG153910-03	51	52	Secreted protein
				CGI-100
NOV5a	CG158564-02	53	54	Interferon induced
				transmembrane
NOV5b	CG158564-01	55	56	Interferon induced
				transmembrane
NOV6a	CG159093-01	57	58	Type Ib membrane
				protein
NOV6b	CG159093-02	59	60	Type Ib membrane
				protein
NOV6c	CG159093-03	61	62	Type Ib membrane
				protein
NOV7a	CG159390-01	63	64	Thrombospondin type
				I domain containing
				protein
NOV8a	CG159498-01	65	66	ST7L isoform 4
				membrane protein
NOV8b	CG159498-02	67	68	ST7L isoform-4
				membrane protein
NOV9a	CG160152-01	69	70	MS4A7
NOV9b	CG160152-03	71	72	MS4A7
NOV9c	CG160152-02	73	74	MS4A7
NOV9d	CG160152-04	75	76	MS4A7
NOV9e	CG160152-05	77	78	MS4A7
NOV10a	CG160185-01	79	80	Membrane protein
NOV11a	CG160244-01	81	82	Type IIIa membrane
				protein
NOV12a	CG160541-01	83	84	Lectin C-type and SCP
				domain containing
				extracellular protein
NOV13a	CG161630-01	85	86	Soggy-1 protein
				precursor
NOV13b	CG161630-02	87	88	Soggy-1 protein
				precursor
NOV14a	CG161793-01	89	90	LME-4 membrane
				protein
NOV15a	CG162177-01	91	92	Folate receptor beta
NOV15b	CG162177-02	93	94	Folate receptor beta
NOV16a	CG162443-02	95	96	Advanced glyco-
				sylation end product-
				specific receptor
NOV16b	CG162443-01	97	98	Advanced glyco-
				sylation end product-
				specific receptor
NOV16c	CG162443-03	99	100	Advanced glyco-
				sylation end product-
				specific receptor
NOV17a	CG162509-02	101	102	Leukocyte-associated
				IG-like receptor-2
NOV17b	306610228	103	104	Leukocyte-associated
				IG-like receptor-2
NOV17c	306610270	105	106	Leukocyte-associated
				IG-like receptor-2
NOV17d	CG162509-01	107	108	Leukocyte-associated
				IG-like receptor-2
NOV18a	CG162645-02	109	110	Cell surface receptor
				FDF03-dtm
NOV18b	CG162645-01	111	112	Cell surface receptor
				FDF03-dtm
NOV19a	CG162687-02	113	114	EVIN2
NOV19b	CG162687-01	115	116	Membrane protei
NOV20a	CG162738-01	117	118	MADSO1
NOV20b	CG162738-02	119	120	MADSO1
NOV20c	CG162738-03	121	122	MADSO1
NOV21a	CG163175-01	123	124	Type Ib membrane
				protein
NOV22a	CG163259-01	125	126	Cytokine-like factor-1
NOV22b	CG163259-02	127	128	Cytokine-like factor-1
NOV22c	CG163259-03	129	130	Cytokine-like factor-1
NOV23a	CG163425-01	131	132	Interleukin-15 receptor
				alpha chain precursor
NOV23b	CG163425-02	133	134	Interleukin-15 receptor
				alpha chain precursor
NOV24a	CG163957-01	135	136	Polycystic kidney and
				hepatic disease 1
				precursor
NOV25a	CG164482-01	137	138	4930418P06RIK
				rhomboid
NOV26a	CG164511-01	139	140	Dora protein precursor
NOV27a	CG55060-03	141	142	SLP1
NOV27b	CG55060-01	143	144	SLP1
NOV27c	CG55060-02	145	146	SLP1
NOV28a	CG56972-02	147	148	NMB
NOV28b	CG56972-03	149	150	NMB
NOV28c	CG56972-01	151	152	NMB
NOV28d	255623772	153	154	NMB

[0038] 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.

[0039] 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), vascular calcification, fibrosis, 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, osteoarthritis, rheumatoid arthritis, osteochondrodysplasia, adrenoleukodystrophy, congenital adrenal hyperplasia, prostate cancer, diabetes, metabolic disorders, neoplasm; adenocarcinoma, lymphoma, uterus cancer, fertility, glomerulonephritis, hemophilia, hypercoagulation, idiopathic thrombocytopenic purpura, immunodeficiencies, psoriasis, skin disorders, graft versus host disease, AIDS, bronchial asthma, lupus, Crohn's disease; inflammatory bowel disease, ulcerative colitis, 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,] schizophrenia, depression, asthma, emphysema, allergies, the metabolic syndrome X and wasting disorders associated with chronic diseases and various cancers, as well as conditions such as transplantation, neuroprotection, fertility, or regeneration (in vitro and in vivo).

[0040] 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.

[0041] 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.

[0042] 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.

[0043] 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.

[0044] Additional utilities for NOVX nucleic acids and polypeptides according to the invention are disclosed herein.

[0045] NOVX Clones

[0046] 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.

[0047] 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.

[0048] 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.

[0049] 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 77; (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 77, 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 77; (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 77 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).

[0050] 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 77; (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 77 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 77; (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 77, 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 77 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.

[0051] 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 77; (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 77 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 77; 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 77 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.

[0052] NOVX Nucleic Acids and Polypeptides

[0053] 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.

[0054] 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.

[0055] 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.

[0056] 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.

[0057] 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 77, 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 77, 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.)

[0058] 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.

[0059] 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 77, or a complement thereof. Oligonucleotides may be chemically synthesized and may also be used as probes.

[0060] 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 77, 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 77, is one that is sufficiently complementary to the nucleotide sequence of SEQ ID NO:2n−1, wherein n is an integer between 1 and 77, 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 77, thereby forming a stable duplex.

[0061] As used herein, the term “complementary” refers to Watson-Crick or Hoogsteen base pairing between nucleotides units of a nucleic acid molecule, and the term “binding” means the physical or chemical interaction between two polypeptides or compounds or associated polypeptides or compounds or combinations thereof. Binding includes ionic, non-ionic, van der Waals, hydrophobic interactions, and the like. A physical interaction can be either direct or indirect. Indirect interactions may be through or due to the effects of another polypeptide or compound. Direct binding refers to interactions that do not take place through, or due to, the effect of another polypeptide or compound, but instead are without other substantial chemical intermediates.

[0062] 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.

[0063] 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.

[0064] 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.

[0065] 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.

[0066] 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 77, as well as a polypeptide possessing NOVX biological activity. Various biological activities of the NOVX proteins are described below.

[0067] 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.

[0068] 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 77; or an anti-sense strand nucleotide sequence of SEQ ID NO:2n−1, wherein n is an integer between 1 and 77; or of a naturally occurring mutant of SEQ ID NO:2n−1, wherein n is an integer between 1 and 77.

[0069] 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.

[0070] “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 77, 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.

[0071] NOVX Nucleic Acid and Polypeptide Variants

[0072] 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 77, 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 77. 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 77.

[0073] In addition to the human NOVX nucleotide sequences of SEQ ID NO:2n−1, wherein n is an integer between 1 and 77, 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.

[0074] 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 77, 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.

[0075] 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 77. 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.

[0076] 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.

[0077] 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.

[0078] 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 77, corresponds to a naturally-occurring nucleic acid molecule. As used herein, a “naturally-occurring” nucleic acid molecule refers to an RNA or DNA molecule having a nucleotide sequence that occurs in nature (e.g., encodes a natural protein).

[0079] 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 77, or fragments, analogs or derivatives thereof, under conditions of moderate stringency is provided. A non-limiting example of moderate stringency hybridization conditions are hybridization in 6×SSC, 5× Reinhardt's solution, 0.5% SDS and 100 mg/ml denatured salmon sperm DNA at 55° C., followed by one or more washes in 1×SSC, 0.1% SDS at 37° C. Other conditions of moderate stringency that may be used are well-known within the art. See, e.g., Ausubel, et al. (eds.), 1993, Current Protocols in Molecular Biology, John Wiley & Sons, NY, and Krieger, 1990; Gene Transfer and Expression, A Laboratory Manual, Stockton Press, NY.

[0080] 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 77, or fragments, analogs or derivatives thereof, under conditions of low stringency, is provided. A non-limiting example of low stringency hybridization conditions are hybridization in 35% formamide, 5×SSC, 50 mM Tris-HCl (pH 7.5), 5 mM EDTA, 0.02% PVP, 0.02% Ficoll, 0.2% BSA, 100 mg/ml denatured salmon sperm DNA, 10% (wt/vol) dextran sulfate at 40° C., followed by one or more washes in 2×SSC, 25 mM Tris-HCl (pH 7.4), 5 mM EDTA, and 0.1% SDS at 50° C. Other conditions of low stringency that may be used are well known in the art (e.g., as employed for cross-species hybridizations). See, e.g., Ausubel, et al. (eds.), 1993, Current Protocols in Molecular Biology, John Wiley & Sons, NY, and Kriegler, 1990, Gene Transfer and Expression, A Laboratory Manual, Stockton Press, NY; Shilo and Weinberg, 1981. Proc Natl Acad Sci USA 78: 6789-6792.

[0081] Conservative Mutations

[0082] 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 77, 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 77. 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.

[0083] 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 77, 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 77. 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 77; more preferably at least about 70% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 77; still more preferably at least about 80% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 77; even more preferably at least about 90% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 77; and most preferably at least about 95% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 77.

[0084] 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 77, 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 77, such that one or more amino acid substitutions, additions or deletions are introduced into the encoded protein.

[0085] Mutations can be introduced any one of SEQ ID NO:2n−1, wherein n is an integer between 1 and 77, by standard techniques, such as site-directed mutagenesis and PCR-mediated mutagenesis. Preferably, conservative amino acid substitutions are made at one or more predicted, non-essential amino acid residues. A “conservative amino acid substitution” is one in which the amino acid residue is replaced with an amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined within the art. These families include amino acids with basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine). Thus, a predicted non-essential amino acid residue in the NOVX protein is replaced with another amino acid residue from the same side chain family. Alternatively, in another embodiment, mutations can be introduced randomly along all or part of a NOVX coding sequence, such as by saturation mutagenesis, and the resultant mutants can be screened for NOVX biological activity to identify mutants that retain activity. Following mutagenesis of a nucleic acid of SEQ ID NO:2n−1, wherein n is an integer between 1 and 77, the encoded protein can be expressed by any recombinant technology known in the art and the activity of the protein can be determined.

[0086] 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.

[0087] 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).

[0088] 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).

[0089] Interfering RNA

[0090] 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.

[0091] 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.

[0092] 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.

[0093] 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.

[0094] In a specific embodiment, siRNAs are transcribed intracellularly by cloning the NOVX gene templates into a vector containing, e.g., a RNA pol III transcription unit from the smaller nuclear RNA (snRNA) U6 or the human RNase P RNA H1. One example of a vector system is the GeneSuppressor™ RNA Interference kit (commercially available from Imgenex). The U6 and H1 promoters are members of the type III class of Pol III promoters. The +1 nucleotide of the U6-like promoters is always guanosine, whereas the +1 for H1 promoters is adenosine. The termination signal for these promoters is defined by five consecutive thymidines. The transcript is typically cleaved after the second uridine. Cleavage at this position generates a 3′ UU overhang in the expressed siRNA, which is similar to the 3′ overhangs of synthetic siRNAs. Any sequence less than 400 nucleotides in length can be transcribed by these promoter, therefore they are ideally suited for the expression of around 21-nucleotide siRNAs in, e.g., an approximately 50-nucleotide RNA stem-loop transcript.

[0095] 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.

[0096] 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.

[0097] 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.

[0098] 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.

[0099] 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.

[0100] 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.

[0101] 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.

[0102] 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.

[0103] 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.

[0104] 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.

[0105] 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.

[0106] 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.

[0107] Where the NOVX gene function is not correlated with a known phenotype, a control sample of cells or tissues from healthy individuals provides a reference standard for determining NOVX expression levels. Expression levels are detected using the assays described, e.g., RT-PCR, Northern blotting, Western blotting, ELISA, and the like. A subject sample of cells or tissues is taken from a mammal, preferably a human subject, suffering from a disease state. The NOVX ribopolynucleotide is used to produce siRNA constructs, that are specific for the NOVX gene product. These cells or tissues are treated by administering NOVX siRNA's to the cells or tissues by methods described for the transfection of nucleic acids into a cell or tissue, and a change in NOVX polypeptide or polynucleotide expression is observed in the subject sample relative to the control sample, using the assays described. This NOVX gene knockdown approach provides a rapid method for determination of a NOVX minus (NOVX) phenotype in the treated subject sample. The NOVX-phenotype observed in the treated subject sample thus serves as a marker for monitoring the course of a disease state during treatment.

[0108] 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.

[0109] Production of RNAs

[0110] 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).

[0111] Lysate Preparation

[0112] 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.

[0113] 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.

[0114] 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.

[0115] RNA Preparation

[0116] 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)).

[0117] 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.

[0118] Cell Culture

[0119] 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.

[0120] 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.

[0121] Antisense Nucleic Acids

[0122] 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 77, 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 77, 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 77, are additionally provided.

[0123] 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).

[0124] 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).

[0125] 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).

[0126] 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.

[0127] In yet another embodiment, the antisense nucleic acid molecule of the invention is an α-anomeric nucleic acid molecule. An α-anomeric nucleic acid molecule forms specific double-stranded hybrids with complementary RNA in which, contrary to the usual β-units, the strands run parallel to each other. See, e.g., Gaultier, et al., 1987. Nucl. Acids Res. 15: 6625-6641. The antisense nucleic acid molecule can also comprise a 2′-o-methylribonucleotide (See, e.g., Inoue, et al. 1987. Nucl. Acids Res. 15: 6131-6148) or a chimeric RNA-DNA analogue (See, e.g., Inoue, et al., 1987. FEBS Lett. 215: 327-330.

[0128] Ribozymes and PNA Moieties

[0129] 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.

[0130] 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 77). 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.

[0131] 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.

[0132] In various embodiments, the NOVX nucleic acids can be modified at the base moiety, sugar moiety or phosphate backbone to improve, e.g., the stability, hybridization, or solubility of the molecule. For example, the deoxyribose phosphate backbone of the nucleic acids can be modified to generate peptide nucleic acids. See, e.g., Hyrup, et al., 1996. Bioorg Med Chem 4: 5-23. As used herein, the terms “peptide nucleic acids” or “PNAs” refer to nucleic acid mimics (e.g., DNA mimics) in which the deoxyribose phosphate backbone is replaced by a pseudopeptide backbone and only the four natural nucleotide bases are retained. The neutral backbone of PNAs has been shown to allow for specific hybridization to DNA and RNA under conditions of low ionic strength. The synthesis of PNA oligomer can be performed using standard solid phase peptide synthesis protocols as described in Hyrup, et al., 1996. supra; Perry-O'Keefe, et al., 1996. Proc. Natl. Acad. Sci. USA 93: 14670-14675.

[0133] 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).

[0134] 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.

[0135] In other embodiments, the oligonucleotide may include other appended groups such as peptides (e.g., for targeting host cell receptors in vivo), or agents facilitating transport across the cell membrane (see, e.g., Letsinger, et al., 1989. Proc. Natl. Acad. Sci. U.S.A. 86: 6553-6556; Lemaitre, et al., 1987. Proc. Natl. Acad. Sci. 84: 648-652; PCT Publication No. WO88/09810) or the blood-brain barrier (see, e.g., PCT Publication No. WO 89/10134). In addition, oligonucleotides can be modified with hybridization triggered cleavage agents (see, e.g., Krol, et al., 1988. BioTechniques 6:958-976) or intercalating agents (see, e.g., Zon, 1988. Pharm. Res. 5: 539-549). To this end, the oligonucleotide may be conjugated to another molecule, e.g., a peptide, a hybridization triggered cross-linking agent, a transport agent, a hybridization-triggered cleavage agent, and the like.

[0136] NOVX Polypeptides

[0137] 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 77. 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 77, while still encoding a protein that maintains its NOVX activities and physiological functions, or a functional fragment thereof.

[0138] 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.

[0139] 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.

[0140] 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.

[0141] 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.

[0142] 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 77) 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.

[0143] 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.

[0144] In an embodiment, the NOVX protein has an amino acid sequence of SEQ ID NO:2n, wherein n is an integer between 1 and 77. In other embodiments, the NOVX protein is substantially homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 77, and retains the functional activity of the protein of SEQ ID NO:2n, wherein n is an integer between 1 and 77, 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 77, and retains the functional activity of the NOVX proteins of SEQ ID NO:2n, wherein n is an integer between 1 and 77.

[0145] Determining Homology Between Two or More Sequences

[0146] 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”).

[0147] 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 77.

[0148] 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.

[0149] Chimeric and Fusion Proteins

[0150] 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 77, 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.

[0151] 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.

[0152] 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.

[0153] 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.

[0154] 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.

[0155] NOVX Agonists and Antagonists

[0156] 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.

[0157] 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.

[0158] Polypeptide Libraries

[0159] 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.

[0160] 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.

[0161] Anti-NOVX Antibodies

[0162] 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.

[0163] 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.

[0164] 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 77, 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.

[0165] 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.

[0166] 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.

[0167] 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.

[0168] Various procedures known within the art may be used for the production of polyclonal or monoclonal antibodies directed against a protein of the invention, or against derivatives, fragments, analogs homologs or orthologs thereof (see, for example, Antibodies: A Laboratory Manual, Harlow E, and Lane D, 1988, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., incorporated herein by reference). Some of these antibodies are discussed below.

[0169] Polyclonal Antibodies

[0170] 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).

[0171] 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).

[0172] Monoclonal Antibodies

[0173] 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.

[0174] 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.

[0175] 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.

[0176] Preferred immortalized cell lines are those that fuse efficiently, support stable high level expression of antibody by the selected antibody-producing cells, and are sensitive to a medium such as HAT medium. More preferred immortalized cell lines are murine myeloma lines, which can be obtained, for instance, from the Salk Institute Cell Distribution Center, San Diego, Calif. and the American Type Culture Collection, Manassas, Va. Human myeloma and mouse-human heteromyeloma cell lines also have been described for the production of human monoclonal antibodies (Kozbor, J. Immunol., 133:3001 (1984); Brodeur et al., Monoclonal Antibody Production Techniques and Applications, Marcel Dekker, Inc., New York, (1987) pp. 51-63).

[0177] 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.

[0178] 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.

[0179] 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.

[0180] 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.

[0181] Humanized Antibodies

[0182] 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)).

[0183] Human Antibodies

[0184] 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).

[0185] 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)).

[0186] 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.

[0187] 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.

[0188] 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.

[0189] 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.

[0190] Fab Fragments and Single Chain Antibodies

[0191] According to the invention, techniques can be adapted for the production of single-chain antibodies specific to an antigenic protein of the invention (see e.g., U.S. Pat. No. 4,946,778). In addition, methods can be adapted for the construction of Fab expression libraries (see e.g., Huse, et al., 1989 Science 246: 1275-1281) to allow rapid and effective identification of monoclonal Fab fragments with the desired specificity for a protein or derivatives, fragments, analogs or homologs thereof. Antibody fragments that contain the idiotypes to a protein antigen may be produced by techniques known in the art including, but not limited to: (i) an F(ab′)2 fragment produced by pepsin digestion of an antibody molecule; (ii) an Fab fragment generated by reducing the disulfide bridges of an F(ab′)2 fragment; (iii) an Fab fragment generated by the treatment of the antibody molecule with papain and a reducing agent and (iv) Fv fragments.

[0192] Bispecific Antibodies

[0193] 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.

[0194] Methods for making bispecific antibodies are known in the art. Traditionally, the recombinant production of bispecific antibodies is based on the co-expression of two immunoglobulin heavy-chain/light-chain pairs, where the two heavy chains have different specificities (Milstein and Cuello, Nature, 305:537-539 (1983)). Because of the random assortment of immunoglobulin heavy and light chains, these hybridomas (quadromas) produce a potential mixture of ten different antibody molecules, of which only one has the correct bispecific structure. The purification of the correct molecule is usually accomplished by affinity chromatography steps. Similar procedures are disclosed in WO 93/08829, published May 13, 1993, and in Traunecker et al., EMBO J., 10:3655-3659 (1991).

[0195] 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).

[0196] 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.

[0197] 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.

[0198] 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.

[0199] 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).

[0200] Antibodies with more than two valencies are contemplated. For example, trispecific antibodies can be prepared. Tutt et al., J. Immunol. 147:60 (1991).

[0201] Exemplary bispecific antibodies can bind to two different epitopes, at least one of which originates in the protein antigen of the invention. Alternatively, an anti-antigenic arm of an immunoglobulin molecule can be combined with an arm which binds to a triggering molecule on a leukocyte such as a T-cell receptor molecule (e.g. CD2, CD3, CD28, or B7), or Fc receptors for IgG (FcγR), such as FcγRI (CD64), FcγRII-(CD32) and FcγRIII (CD16) so as to focus cellular defense mechanisms to the cell expressing the particular antigen. Bispecific antibodies can also be used to direct cytotoxic agents to cells which express a particular antigen. These antibodies possess an antigen-binding arm and an arm which binds a cytotoxic agent or a radionuclide chelator, such as EOTUBE, DPTA, DOTA, or TETA. Another bispecific antibody of interest binds the protein antigen described herein and further binds tissue factor (TF).

[0202] Heteroconjugate Antibodies

[0203] 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.

[0204] Effector Function Engineering

[0205] 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).

[0206] Immunoconjugates

[0207] 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).

[0208] 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.

[0209] 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.

[0210] 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.

[0211] Immunoliposomes

[0212] The antibodies disclosed herein can also be formulated as immunoliposomes. Liposomes containing the antibody are prepared by methods known in the art, such as described in Epstein et al., Proc. Natl. Acad. Sci. USA, 82: 3688 (1985); Hwang et al., Proc. Natl Acad. Sci. USA, 77: 4030 (1980); and U.S. Pat. Nos. 4,485,045 and 4,544,545. Liposomes with enhanced circulation time are disclosed in U.S. Pat. No. 5,013,556.

[0213] 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).

[0214] Diagnostic Applications of Antibodies Directed Against the Proteins of the Invention

[0215] 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.

[0216] 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”).

[0217] 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 streptavidinibiotin and avidinibiotin; examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin, and examples of suitable radioactive material include 125I, 131I, 35S or 3H.

[0218] Antibody Therapeutics

[0219] 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.

[0220] 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.

[0221] 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.

[0222] Pharmaceutical Compositions of Antibodies

[0223] 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.

[0224] 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.

[0225] 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.

[0226] The formulations to be used for in vivo administration must be sterile. This is readily accomplished by filtration through sterile filtration membranes.

[0227] 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.

[0228] ELISA Assay

[0229] 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 Theory 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.

[0230] NOVX Recombinant Expression Vectors and Host Cells

[0231] 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.

[0232] 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).

[0233] 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.).

[0234] 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.

[0235] 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.

[0236] 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).

[0237] One strategy to maximize recombinant protein expression in E. coli is to express the protein in a host bacteria with an impaired capacity to proteolytically cleave the recombinant protein. See, e.g., Gottesman, Gene Expression Technology: Methods in Enzymology 185, Academic Press, San Diego, Calif. (1990) 119-128. Another strategy is to alter the nucleic acid sequence of the nucleic acid to be inserted into an expression vector so that the individual codons for each amino acid are those preferentially utilized in E. coli (see, e.g., Wada, et al., 1992. Nucl. Acids Res. 20: 2111-2118). Such alteration of nucleic acid sequences of the invention can be carried out by standard DNA synthesis techniques.

[0238] In another embodiment, the NOVX expression vector is a yeast expression vector. Examples of vectors for expression in yeast Saccharomyces cerivisae include pYepSec1 (Baldari, et al., 1987. EMBO J. 6: 229-234), pMFa (Kuijan and Herskowitz, 1982. Cell 30: 933-943), pJRY88 (Schultz et al., 1987. Gene 54: 113-123), pYES2 (Invitrogen Corporation, San Diego, Calif.), and picZ (InVitrogen Corp, San Diego, Calif.).

[0239] 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).

[0240] 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.

[0241] 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 (Banelji, et al., 1983. Cell 33: 729-740; Queen and Baltimore, 1983. Cell 33: 741-748), neuron-specific promoters (e.g., the neurofilament promoter; Byrne and Ruddle, 1989. Proc. Natl. Acad. Sci. USA 86: 5473-5477), pancreas-specific promoters (Edlund, et al., 1985. Science 230: 912-916), and mammary gland-specific promoters (e.g., milk whey promoter; U.S. Pat. No. 4,873,316 and European Application Publication No. 264,166). Developmentally-regulated promoters are also encompassed, e.g., the murine hox promoters (Kessel and Gruss, 1990. Science 249: 374-379) and the α-fetoprotein promoter (Campes and Tilghman, 1989. Genes Dev. 3: 537-546).

[0242] 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.

[0243] 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.

[0244] 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.

[0245] 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.

[0246] 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).

[0247] 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.

[0248] Transgenic NOVX Animals

[0249] 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.

[0250] 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 77, 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.

[0251] 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 77), 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 77, 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).

[0252] 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.

[0253] 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.

[0254] 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.

[0255] Clones of the non-human transgenic animals described herein can also be produced according to the methods described in Wilmut, et al., 1997. Nature 385: 810-813. In brief, a cell (e.g., a somatic cell) from the transgenic animal can be isolated and induced to exit the growth cycle and enter G0 phase. The quiescent cell can then be fused, e.g., through the use of electrical pulses, to an enucleated oocyte from an animal of the same species from which the quiescent cell is isolated. The reconstructed oocyte is then cultured such that it develops to morula or blastocyte and then transferred to pseudopregnant female foster animal. The offspring borne of this female foster animal will be a clone of the animal from which the cell (e.g., the somatic cell) is isolated.

[0256] Pharmaceutical Compositions

[0257] 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.

[0258] 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.

[0259] 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.

[0260] 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.

[0261] Oral compositions generally include an inert diluent or an edible carrier. They can be enclosed in gelatin capsules or compressed into tablets. For the purpose of oral therapeutic administration, the active compound can be incorporated with excipients and used in the form of tablets, troches, or capsules. Oral compositions can also be prepared using a fluid carrier for use as a mouthwash, wherein the compound in the fluid carrier is applied orally and swished and expectorated or swallowed. Pharmaceutically compatible binding agents, and/or adjuvant materials can be included as part of the composition. The tablets, pills, capsules, troches and the like can contain any of the following ingredients, or compounds of a similar nature: a binder such as microcrystalline cellulose, gum tragacanth or gelatin; an excipient such as starch or lactose, a disintegrating agent such as alginic acid, Primogel, or corn starch; a lubricant such as magnesium stearate or Sterotes; a glidant such as colloidal silicon dioxide; a sweetening agent such as sucrose or saccharin; or a flavoring agent such as peppermint, methyl salicylate, or orange flavoring.

[0262] 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.

[0263] Systemic administration can also be by transmucosal or transdermal means. For transmucosal or transdermal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art, and include, for example, for transmucosal administration, detergents, bile salts, and fusidic acid derivatives. Transmucosal administration can be accomplished through the use of nasal sprays or suppositories. For transdermal administration, the active compounds are formulated into ointments, salves, gels, or creams as generally known in the art.

[0264] 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.

[0265] 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.

[0266] 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.

[0267] 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.

[0268] The pharmaceutical compositions can be included in a container, pack, or dispenser together with instructions for administration.

[0269] Screening and Detection Methods

[0270] 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.

[0271] The invention further pertains to novel agents identified by the screening assays described herein and uses thereof for treatments as described, supra.

[0272] Screening Assays

[0273] 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.

[0274] 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.

[0275] 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.

[0276] 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.

[0277] 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.).

[0278] 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.

[0279] 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.

[0280] 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.

[0281] 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.

[0282] 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.

[0283] 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.

[0284] 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).

[0285] 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.

[0286] Other techniques for immobilizing proteins on matrices can also be used in the screening assays of the invention. For example, either the NOVX protein or its target molecule can be immobilized utilizing conjugation of biotin and streptavidin. Biotinylated NOVX protein or target molecules can be prepared from biotin-NHS (N-hydroxy-succinimide) using techniques well-known within the art (e.g., biotinylation kit, Pierce Chemicals, Rockford, Ill.), and immobilized in the wells of streptavidin-coated 96 well plates (Pierce Chemical). Alternatively, antibodies reactive with NOVX protein or target molecules, but which do not interfere with binding of the NOVX protein to its target molecule, can be derivatized to the wells of the plate, and unbound target or NOVX protein trapped in the wells by antibody conjugation. Methods for detecting such complexes, in addition to those described above for the GST-immobilized complexes, include immunodetection of complexes using antibodies reactive with the NOVX protein or target molecule, as well as enzyme-linked assays that rely on detecting an enzymatic activity associated with the NOVX protein or target molecule.

[0287] 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.

[0288] 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.

[0289] 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.

[0290] The invention further pertains to novel agents identified by the aforementioned screening assays and uses thereof for treatments as described herein.

[0291] Detection Assays

[0292] 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.

[0293] Chromosome Mapping

[0294] 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 77, 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.

[0295] 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.

[0296] 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.

[0297] 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.

[0298] 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).

[0299] 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.

[0300] 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.

[0301] 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.

[0302] Tissue Typing

[0303] 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).

[0304] 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.

[0305] 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).

[0306] 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 77, are used, a more appropriate number of primers for positive individual identification would be 500-2,000.

[0307] Predictive Medicine

[0308] 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.

[0309] 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.)

[0310] 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.

[0311] These and other agents are described in further detail in the following sections.

[0312] Diagnostic Assays

[0313] An exemplary method for detecting the presence or absence of NOVX in a biological sample involves obtaining a biological sample from a test subject and contacting the biological sample with a compound or an agent capable of detecting NOVX protein or nucleic acid (e.g., mRNA, genomic DNA) that encodes NOVX protein such that the presence of NOVX is detected in the biological sample. An agent for detecting NOVX mRNA or genomic DNA is a labeled nucleic acid probe capable of hybridizing to NOVX mRNA or genomic DNA. The nucleic acid probe can be, for example, a full-length NOVX nucleic acid, such as the nucleic acid of SEQ ID NO:2n−1, wherein n is an integer between 1 and 77, 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.

[0314] 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.

[0315] 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.

[0316] 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.

[0317] 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.

[0318] Prognostic Assays

[0319] 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.

[0320] 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).

[0321] 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.

[0322] 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.

[0323] 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.

[0324] 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.

[0325] 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.

[0326] 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).

[0327] Other methods for detecting mutations in the NOVX gene include methods in which protection from cleavage agents is used to detect mismatched bases in RNA/RNA or RNA/DNA heteroduplexes. See, e.g., Myers, et al., 1985. Science 230: 1242. In general, the art technique of “mismatch cleavage” starts by providing heteroduplexes of formed by hybridizing (labeled) RNA or DNA containing the wild-type NOVX sequence with potentially mutant RNA or DNA obtained from a tissue sample. The double-stranded duplexes are treated with an agent that cleaves single-stranded regions of the duplex such as which will exist due to basepair mismatches between the control and sample strands. For instance, RNA/DNA duplexes can be treated with RNase and DNA/DNA hybrids treated with S1 nuclease to enzymatically digesting the mismatched regions. In other embodiments, either DNA/DNA or RNA/DNA duplexes can be treated with hydroxylamine or osmium tetroxide and with piperidine in order to digest mismatched regions. After digestion of the mismatched regions, the resulting material is then separated by size on denaturing polyacrylamide gels to determine the site of mutation. See, e.g., Cotton, et al., 1988. Proc. Natl. Acad. Sci. USA 85: 4397; Saleeba, et al., 1992. Methods Enzymol. 217: 286-295. In an embodiment, the control DNA or RNA can be labeled for detection.

[0328] 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.

[0329] 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.

[0330] 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.

[0331] 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.

[0332] 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.

[0333] 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.

[0334] 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.

[0335] Pharmacogenomics

[0336] 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.

[0337] 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.

[0338] 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.

[0339] 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.

[0340] 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.

[0341] Monitoring of Effects During Clinical Trials

[0342] 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.

[0343] 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.

[0344] 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.

[0345] Methods of Treatment

[0346] 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.

[0347] These methods of treatment will be discussed more fully, below.

[0348] Diseases and Disorders

[0349] 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.

[0350] 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.

[0351] 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).

[0352] Prophylactic Methods

[0353] 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.

[0354] Therapeutic Methods

[0355] 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.

[0356] 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 gestation al disease (e.g., preclampsia).

[0357] Determination of the Biological Effect of the Therapeutic

[0358] 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.

[0359] 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.

[0360] Prophylactic and Therapeutic Uses of the Compositions of the Invention

[0361] 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.

[0362] 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.

[0363] 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.

[0364] 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

[0365] Polynucleotide and Polypeptide Sequences, and Homology Data

[0366] 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	531 bp
NOV1a,	ATGAAGCCCCTGCTCCTGGCCGTCAGCCTTGGCCTCATTGCTGCCCTGCAGGCCCACCACCTCCTGGC
CG102689-01
DNA Sequence	CTCAGACGAGGAGATTCAGGATGTGTCAGGACGTGGTATCTGAAGGCCATGACGGTGGACAGGGAGT
	TCCCTGAGATGAATCTGGAATCGGTGACACCCATGACCCTCACGACCCTGGAAGGGGGCAACCTGGAA
	GCCAAGGTCACCATGCTGATAAGTGGCCGGTGCCAGGAGGTGAAGGCCGTCCTGGAGAAAACTGACGA
	GCCGGGAAAATACACGGCCGACGGGGGCAAGCACGTGGCATACATCATCAGGTCGCACGTGAAGGACC
	ACTACATCTTTTACTGTGAGGGCGAGCTGCACGGGAAGCCGGTCCGAGGGGTGAAGCTCGTGGGCAGA
	GACCCCAAGAACAACCTGGAAGCCTTGGAGGACTTTGAGAAAGCCGCAGGAGCCCGCGGACTCAGCAC
	GGAGAGCATCCTCATCCCCAGGCAGAGCGAAACCTGCTCTCCAGGGAGCGATTAG
	ORF Start: ATG at 1		ORF Stop: TAG at 529
	SEQ ID NO:2	176 aa	MW at 19249.8 kD
NOV1a,	MKPLLLAVSLGLIAALQAHHLLASDEEIQDVSGTWYLKAMTVDREFPEMNLESVTPMTLTTLECGNLE
CG102689-01	AKVTMLISGRCQEVKAVLEKTDEPGKYTADGGKHVAYIIRSHVKDHYIFYCEGELHGKPVRGVKLVGR
Protein
Sequence	DPKNNLEALEDFEKAAGARGLSTESILIPRQSETCSPGSD
	SEQ ID NO:3	531 bp
NOV1b,	CGTGGACTCAGACTCCGGAGATGAAGCCCCTGCTCCTGGCCGTCAGCCTTGGCCTCATTGCTGCCCT
CG102689-02
DNA Sequence	GCAGGCCCACCACCTCCTGGCCTCACACGACGAGATTCAGGATGTGTCAGGGACGTGGTATCTGAAG
	GCCATGACCGTGGACACGGAGTTCCCTGAGATGAATCTCGAATCGGTGACACCCATGACCCTCACGA
	CCCTGQAAGCGGGCAACCTGGAAGCCAAGGTCACCATGCTGATAAGTGGCCGGTGCCAGGAGGTGAA
	GGCCGTCCTGGAGAAAACTGACGAGCCGGTCCGAGGGGTGAAGCTCGTCGGCAGAGACCCCAAGAAC
	AACCTGGAACCCTTGGACGACTTTGAGAAAGCCGCAGGAGCCCGCGGACTCAGCACGGACAGCATCC
	TCATCCCCACGCAGAGCGAAACCTGCTCTCCAGGGAGCGATTAGGGGCAGGGGACACCTTGGCTCCT
	CAGCAGCCCAAGGACGGCACCATCCAGCACCTCCGTCATTCACAGGGACATGGAAAAGCTCC
	ORF Start: ATG at 21		ORF Stop: TAG at 444
	SEQ ID NO:4	141 aa	MW at 15277.3 kD
NOV1b,	MKPLLLAVSLGLIAALQAHHLLASDEEIQDVSGTWYLKAMTVDREFPEMNLESVTPMTLTTLEGGNL
CG102689-02
Protein	EAKVTMLISGRCQEVKAVLEKTDEPVRGVKLVGRDPKNNLEALEDFEKAAGARGLSTESILIPRQSE
Sequence
	TCSPGSD

[0367] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 1B.

TABLE 1B
Comparison of NOV1a against NOV1b.
		NOV1a Residues/	Identities/Similarities
	Protein Sequence	Match Residues	for the Matched Region
	NOV1b	1 . . . 176	141/176 (80%)
		1 . . . 141	141/176 (80%)

[0368] Further analysis of the NOV1a protein yielded the following properties shown in Table 1C.

TABLE 1C
Protein Sequence Properties NOV1a
SignalP
analysis:	Cleavage site between residues 24 and 25
PSORT II	PSG:	a new signal peptide prediction method
analysis:		N-region: length 2; pos. chg 1; neg. chg 0
		H-region: length 22; peak value 9.05
		PSG score: 4.65
	GvH:	von Heijne's method for signal seq. recognition
		GvH score (threshold: −2.1): 1.14
		possible cleavage site: between 15 and 16
	>>> Seems to have a cleavable signal peptide (1 to 15)
	ALOM:	Klein et al's method for TM region allocation
		Init position for calculation: 16
		Tentative number of TMS(s) for the threshold 0.5: 0
		number of TMS(s) . . . fixed
		PERIPHERAL Likelihood = 8.80 (at 59)
		ALOM score: 8.80 (number of TMSs: 0)
	MTOP:	Prediction of membrane topology (Hartmann et al.)
		Center position for calculation: 7
		Charge difference: −5.0 C(−3.0) − N(2.0)
		N > = C: N-terminal side will be inside
	MITDISC: discrimination of mitochondrial targeting seq
		R content:	0	Hyd Moment(75):	5.25
		Hyd Moment(95):	6.66	G content:	1
		D/E content:	1	S/T content:	2
		Score: −4.93
	Gavel:	prediction of cleavage sites for mitochondrial preseq
		cleavage site motif not found
	NUCDISC: discrimination of nuclear localization signals
		pat4: none
		pat7: none
		bipartite: none
		content of basic residues: 10.8%
		NLS Score: −0.47
	KDEL: ER retention motif in the C-terminus: none
	ER Membrane Retention Signals: none
	SKL: peroxisomal targeting signal in the C-terminus: none
	PTS2: 2nd peroxisomal targeting signal: none
	VAC: possible vacuolar targeting motif: none
	RNA-binding motif: none
	Actinin-type actin-binding motif:
		type 1: none
		type 2: none
	NMYR: N-myristoylation pattern: none
	Prenylation motif: none
	memYQRL: transport motif from cell surface to Golgi: none
	Tyrosines in the tail: none
	Dileucine motif in the tail: none
	checking 63 PROSITE DNA binding motifs: none
	checking 71 PROSITE ribosomal protein motifs: none
	checking 33 PROSITE prokaryotic DNA binding motifs: none
	NNCN:	Reinhardt's method for Cytoplasmic/Nuclear
		discrimination
		Prediction: cytoplasmic
		Reliability: 89
	COIL:	Lupas's algorithm to detect coiled-coil regions
		total: 0 residues
	-------------------------------
	Final Results (k = 9/23):
		33.3%: extracellular, including cell wall
		22.2%: mitochondrial
		22.2%: vacuolar
		11.1%: Golgi
		11.1%: endoplasmic reticulum
	>> prediction for CG102689-01 is exc (k = 9)

[0369] A search of the NOV1a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 1D.

TABLE 1D
Geneseq Results for NOV1a
Geneseq	Protein/Organism/Length	NOV1a Residues/	Identities/Similarities	Expect
Identifier	[Patent #, Date]	Match Residues	for the Matched Region	Value
AAG66536	Human interferon-alpha	1 . . . 176	176/176 (100%)	2e−98
	induced polypeptide,	1 . . . 176	176/176 (100%)
	Lipocalin 1 - Homo sapiens,
	176 aa. [WO200159155-A2,
	16-AUG-2001]
ABG29411	Novel human diagnostic	1 . . . 170	157/170 (92%)	4e−87
	protein #29402 - Homo	1 . . . 170	162/170 (94%)
	sapiens, 865 aa.
	[WO200175067-A2,
	11-OCT-2001]
AAY25670	Dog allergen Can f 1 protein	1 . . . 174	100/174 (57%)	3e−48
	fragment - Canis sp, 174 aa.	1 . . . 172	122/174 (69%)
	[WO9934826-A1,
	15-JUL-1999]
AAR59987	Can fI protein allergen -	1 . . . 174	100/174 (57%)	3e−48
	Canis familiaris, 174 aa.	1 . . . 172	122/174 (69%)
	[WO9416068-A,
	21-JUL-1994]
ABB84919	Human PRO1283 protein	1 . . . 173	80/174 (45%)	9e−36
	Homo sapiens, 170 aa.	1 . . . 168	109/174 (61%)
	[WO200200690-A2,
	03-JAN-2002]

[0370] In a BLAST search of public sequence databases, the NOV1a protein was found to have homology to the proteins shown in the BLASTP data in Table 1E.

TABLE 1E
Public BLASTP Results for NOV1a
Protein		NOV1a Residues/	Identities/Similarities	Expect
Accession Number	Protein/Organism/Length	Match Residues	for the Matched Portion	Value
P31025	Von Ebner's gland protein	1 . . . 176	176/176 (100%)	6e−98
	precursor (VEG protein) (Tear	1 . . . 176	176/176 (100%)
	prealbumin) (TP) (Tear
	lipocalin) (Lipocalin 1) -
	Homo sapiens (Human), 176
	aa.
P53715	Von Ebner's gland protein	1 . . . 176	103/176 (58%)	4e−52
	precursor (VEG protein) (Tear	2 . . . 176	131/176 (73%)
	prealbumin) (TP) (Tear
	lipocalin) (Lipocalin-1) - Sus
	scrofa (Pig), 176 aa.
P41244	Von Ebner's gland protein 2	1 . . . 176	107/178 (60%)	9e−51
	precursor (VEG protein 2) -	1 . . . 177	127/178 (71%)
	Rattus norvegicus (Rat), 177
	aa.
P20289	Von Ebner's gland protein 1	1 . . . 176	104/178 (58%)	1e−49
	precursor (VEG protein 1) -	1 . . . 177	125/178 (69%)
	Rattus norvegicus (Rat), 177
	aa.
O18873	Major allergen Can f 1	1 . . . 174	100/174 (57%)	1e−47
	precursor (Allergen Dog 1) -	1 . . . 172	122/174 (69%)
	Canis familiaris (Dog), 174 aa.

[0371] PFam analysis predicts that the NOV1a protein contains the domains shown in the Table 1F.

TABLE 1F
Domain Analysis of NOV1a
		Identities/
		Similarities for	Expect
Pfam Domain	NOV1a Match Region	the Matched Region	Value
Clusterin	1 . . . 13	8/13 (62%)	0.59
		12/13 (92%)
lipocalin	30 . . . 171	45/157 (29%)	7.2e−38
		117/157 (75%)

Example 2

[0372] 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:5	4139 bp
NOV2a,	TCGCGGCCGCCGAGCGCAGTGCCCCGCCGGTCTTACAGGAGAGGGGACCGTCCTGCGCTGGCCTCGAC
CG103827-01
DNA Sequence	CATGGTGCTGCTCTGGGAGCCTGCAGGAGCCTCGCTTGCTCTGGGCCTGGCCCTGGCCCTGGGCCCCA
	GCGTGGCCGCACCTGCCCCTCGGCAGGACTGCACGGGCGTGGAGTGCCCGCCGCTGGACAACTGCATT
	GAGGAGGCGCTGGAGCCGGGTGCCTGCTGTGCCACGTGTGTGCACCAGGGCTGCGCCTGCGAGCGCTA
	CCAGTACTATGACTGCCTACAGGGTGGCTTCGTGCGCGGCCGCGTGCCCGCCGGTCAGTCCTATTTTG
	TGGACTTCGGGAGCACTGAGTGCTCCTGCCCACCAGGCGGCGGCAAGATCAGCTGCCAGTTCATGCTG
	TGCCCGGAGCTGCCGCCCAACTGCATCGACGCTGTAGTGGTGGCTGACAGCTGCCCACAGTGCGGCCA
	GGTGGGCTGCGTCCACGCGGGCCACGAGTACCCCGCTCGCCACACTGTTCACCTGCCGCCCTGCCGCG
	CCTGCCACTGCCCTGACGCCGGTGGAGAGCTCATCTGCTACCAGCTCCCCGGTTGCCACGGGAACTTC
	TCAGATGCCGAGGAGGGTGACCCCGAGCGACACTACGAAGACCCCTACAGCTATGACCACGAGGTGGC
	CGAGGTGGAAGCAGCAACAGCCCTGGGGGGTGAGGTCCACGCGGGTGCAGTCCAGGCAGGCGCACGGG
	GCCCCCCAGCTGCTCTGGGAGGTGCGAGTCAGCCACTGTCCACCATCCAGGCACCCCCCTGGCCAGCT
	GTCCTCCCCAGGCCCACAGCGGCTGCTGCCCTGGGTCCCCCAGCCCCAGTGCAGGCCAAAGCTAGGAG
	AGTGACCGAGCACAGTGAGGAGGAAGAAGAGGAGGAGGAGGAGAGAGAGGAAATGGCTGTCACTGAGC
	AGCTGGCACCACGTGGCCACAGGGGGCTGGATGGGCTGCCCACTACAGCCCCAGCTGGACCCAGTCTT
	CCTATCCAGGAGGAGAGGGCAGAAGCTGGGGCAAGGGCAGAAGCTGGCGCAAGGCCTGAAGAGAACCT
	CATCCTGGATGCCCAAGCCACGTCCCGCAGCACTGCGCCCGAGGGCGTGACGCATGCACCGAGCCTGG
	GCAAGGCTGCTCTCGTCCCAACTCAGGCCGTGCCTGGCTCTCCCAGGGACCCAGTCAAGCCCAGCCCC
	CACAACATCCTGTCCACATCACTGCCTGATGCAGCCTGGATCCCACCCACCCGAGAAGTGCCCAGGAA
	GCCGCAAGTTCTGCCCCATTCCCACGTCGAGGAGGACACACACCCCAACTCTGTCCATTCTATCCCCA
	GAAGTAGCCCTGAAGGCTCCACCAAGGACCTGATCGAGACTTGCTGCGCAGCCGGACAGCAGTGGGCC
	ATTGACAATGACGAGTGCCTGGAGATCCCTGAGAGTGGCACTGAGGACAACGTCTCCAGGACAGCCCA
	GAGGCACTGCTGTCTCTCCTACTTGCAGGAGAAGAGCTGCATGGCCGGCGTCCTGGGAGCCAAGGAGG
	GTGAGACCTGTGGGGCTGAGGACAACGACAGCTGCCGCATCTCCCTGTACAAGCAATGCTGTGACTGC
	TGTGGCCTGGGCCTCCGCGTGCGCGCCGAGGGCCAGTCGTGTGAGTCCAATCCTAACCTGGGCTATCC
	CTGCAATCATGTCATGCTCTCCTGCTGTGAGGGTGAAGAGCCTCTCATAGTACCTGAGGTTCGCCGAC
	CTCCAGAGCCCGCAGCTGCACCACGGAGAGTTTCAGAGGCAGAGATCGCGGGCCCAGAGGCCCTGTCA
	CTGGGCACAGAGGCCGAGCTGCCGAACAGCCTGCCGGGCGATGACCAGGATGAGTGCCTTCTCCTCCC
	GGGAGAGCTGTGCCAGCACCTTTGCATCAATACTGTGGGTTCTTACCACTGTGCCTGCTTTCCTGGCT
	TCTCACTGCAGGACGATGGCCGCACTTGCCGCCCAGACGGTCACCCTCCACAGCCGGAAGCCCCACAG
	GAGCCTGCACTCAAGTCACAATTTTCCCAGGTGGCCTCTAACACCATCCCGCTGCCACTGCCGCAGCC
	CAATACCTGCAAAGACAATGGACCCTGCAAGCAGGTGTGCAGCACTGTTGGGGGCTCAGCCATATGCT
	CCTGTTTTCCCGGCTATGCCATCATGGCGGATGGCGTGTCCTGTGAAGACATCAACGAGTGTGTCACG
	GACCTGCACACGTGCAGCCGGGGCGAGCACTGTGTGAACACACTGGCCTCCTTCCACTGCTACAAGGC
	ACTCACCTGTGAGCCAGGCTATGCCCTCAAGGATGGCGAGTGCGAAGACGTGGATGAGTGTGCGATCG
	GCACGCACACCTGCCAGCCGGGCTTCTTGTGCCAGAACACCAAGGGCTCCTTCTACTGCCAGGCCAGG
	CAGCGCTGCATGGATGGCTTCCTGCAGGATCCTGAAGGCAACTGTGTGGACATCAACGAGTGCACGTC
	ACTGTCCGAGCCATGTCGGCCAGGCTTCAGCTGCATCAACACGGTGGGCTCCTACACGTGCCAGAGGA
	ACCCGCTGATCTQCGCGCGCGGCTACCACGCCAGCGATGATGGGCCCAAGTGTGTGGACGTGAATGAG
	TGTGAGACAGGTGTGCACCGCTGCGGTGAGGGCCAAGTGTGCCACAACCTCCCTGGCTCCTACCGCTG
	TGACTGCAAAGCCGGCTTTCAGCGGGATGCCTTCGGCCGGGGCTGCATCGACGTGAATGAGTGCTGGG
	CCTCGCCACGCCGCCTGTGCCAGCACACGTGTGAGAACAcACTCGGCTCCTACCGCTGTTCCTGCGCC
	TCCGGGTTCCTGCTAGCAGCGGACCGCAAGCGCTGTGAAGACGTGAATGAGTGTGAGGCCCAGCGCTG
	CAGCCAGGAGTGTGCCAACATCTATGGCTCCTACCAGTGCTACTGCCGCCAGGGCTACCAGCTGGCTG
	AGGATGGGCACACCTGCACAGACATCGACGAGTGTGCTCAAGGCGCCGGCATCCTCTGCACCTTCCGC
	TGTCTCAACGTGCCAGGGAGCTACCAGTGTGCATGCCCTGAGCAGGGCTACACCATGACGGCCAACGG
	GAGGTCCTGCAAGGACGTCGATGAGTGTGCACTGGGCACCCACAACTGTTCCGACGCTGAGACCTGCC
	ACAACATCCAGGGTAGCTTCCGCTGCCTGCGCTTCGAGTGTCCTCCCAACTATGTCCAAGTCTCCAAA
	ACGAAGTGCGAGCGCACCACGTGCCATGACTTCCTCGAGTGCCAGAACTCGCCAGCGCGCATCACGCA
	CTACCAGCTCAACTTCCAGACGQGCCTCCTGGTGCCTGCGCATATCTTCCGCATTGGCCCCGCGCCAG
	CCTTCACCGGGGACACCATCGCCCTCAACATCATCAAGGGCAATGAGGAGGGCTACTTTGGCACGCGC
	AGGCTCAATGCCTACACGGGTGTGGTCTACCTGCAGCGGGCCGTGCTGGAGCCCCGGGACTTTGCCCT
	GGACGTGGAGATGAAGCTCTGGAGGCACGGCTCCGTCACCACCTTCCTGGCCAAGATGCACATCTTCT
	TCACCACCTTTGCCCTGTGAGGTGCCAGCACGGGCCACCTGCGGGTGTGGCGCAGCAGGGCTCACAC
	TGCGTGGGAGGGACTGGGTCACTATTGTGGTTTTTACTATAACTTTGTAAATTAACTTAATTTTGCTG
	ACTTGACTCCTGTGGCTTCTGGACCCCTCCTCTGCCCCGCAGGAGGAAGTTCCACGGCAQGTGGTGCC
	TTCCCATGTACGCACCAAGTGGAAGCTTGCACGGTGGGCCACGGCCGTGGCCGGTGCCCTGTCGGTGA
	GGCTGGGTGATGACCTGAGGACCAGAGACACGCGACCATGTTGGGGCTCTTGCACTCCTCTGGATGAC
	CCGTCCCCAAACGTTGACATTCCATTTCATGTTCCACTGTGATTAACTTCTTTTCTTTTTTAAAAAAT
	CATTTTAAAGTTTTTTGTTTAACTATAAAGTAGTACATGTACATTATATAAAAAAAAAGTTCAACTAG
	TATGAAAGGGTTATAAAGTAACAGAGGAAAACGCCTCTTGGTCCCTTTAAAAAAAAAAA
	ORF Start: ATG at 70		ORF Stop: TGA at 3622
	SEQ ID NO:6	1184 aa	MW at 126542.1 kD
NOV2a,	MVLLWEPAGAWLALGLALALGPSVAAAAPRQDCTGVECPPLENCIEEALEPGACCATCVQQGCACEGY
CG103827-01	QYYDCLQGGFVRGRVPAGQSYFVDFGSTECSCPPGGGKISCQFMLCPELPPNCIEAVVVADSCPQCCQ
Protein
Sequence	VGCVHAGHEYAAGHTVHLPPCPACHCPDAGGELICYQLPGCHGNFSDAEEGDPERHYEDPYSYDQEVA
	EVEAATALGCEVQAGAVQAGACGPPAALGGGSQPLSTIQAPPWPAVLPRPTAAAALGPPAPVQAKARR
	VTEDSEEEEEEEEEREEMAVTEQLAACGHRGLDGLPTTAPAGPSLPIQEERAEAQARAEAGARPEENL
	ILDAQATSRSTGPEGVTHAPSLGKAALVPTQAVPGSPRDPVKPSPHNILSTSLPDAAWIPPTREVPRK
	PQVLPHSHVEEDTDPNSVHSIPRSSPEGSTKDLIETCCAAGQQWAIDNDECLEIPESGTEDNVCRTAQ
	RHCCVSYLQEKSCMAGVLGAKEGETCGAEDNDSCGISLYKQCCDCCGLQLRVRAEGOSCESNPNLGYP
	CNHVMLSCCEGEEPLIVPEVRRPPEPAAAPRRVSEAEMAGREALSLGTEAELPNSLPGDDQDECLLLP
	GELCQHLCINTVGSYHCACFPGFSLQDDGRTCRPEGHPPQPEAPQEPALKSEFSQVASNTIPLPLPQP
	NTCKDNGPCKQVCSTVGGSAICSCFPGYAIMADGVSCEDINECVTDLHTCSRGEHCVNTLGSFHCYKA
	LTCEPGYALKDGECEDVDECAMGTHTCQPGFLCQNTKGSFYCQARQRCMDGFLQDPEGNCVDINECTS
	LSEPCRPGFSCINTVGSYTCQRNPLICARGYHASDDGAKCVDVNECETGVHRCGEGQVCHNLPGSYRC
	DCKAGFQRDAPGRGCIDVNECWASPGRLCQHTCENTLGSYRCSCASGFLLAADGKRCEDVNECEAQRC
	SQECANIYGSYQCYCRQGYQLAEDGHTCTDIDECAQGAGILCTFRCLNVPGSYQCACPEQGYTMTANG
	RSCKDVDECALGTHNCSEAETCHNIQGSFRCLRFECPPNYVQVSKTKCERTTCHDFLECQNSPARITH
	YQLNFQTGLLVPAHIFRIGPAPAFTGDTIALNIIKGNEEGYFGTRRLNAYTGVVYLQRAVLEPRDFAL
	DVEMKLWRQGSVTTFLAKMHIFFTTFAL
	SEQ ID NO:7	3980 bp
NOV2b,	TCGCGGCCGCCGAGCGCAGTGCCCCGCGGGTCTTACAGGAGAGGGGACCGTCCTGGGCTGGCCTGGA
CG103827-02
DNA Sequence	CCATGGTGCTGCTCTGCGAGCCTGCAGCAGCCTGGCTTGCTCTGGGCCTGGCCCTGGCCCTCGGCCC
	CAGCGTGGCCGCAGCTGCCCCTCGGCAGGACTGCACGGGCGTGGAGTCCCCGCCGCTGGAGAACTGC
	ATTGACGAGGCGCTCGAGCCGGGTGCCTGCTGTGCCACGTGTGTGCAGCACGGCTGCGCCTGCGAGG
	GCTACCAGTACTATGACTGCCTACACGGTCGCTTCGTGCGCGGCCGCGTGCCCGCCGGTCAGTCCTA
	TTTTGTGGACTTCGGGAGCACTGAGTGCTCCTGCCCACCAGGCCGCCGCAAGATCAGCTGCCAGTTC
	ATGCTGTGCCCGGAGCTGCCGCCCAACTGCATCGAGGCTGTAGTGGTGGCTGACAGCTGCCCACAGT
	GCGGCCAGGTGGGCTCCGTCCACGCGGGCCACGAGTACGCCGCTGGCCACACTGTTCACCTGCCGCC
	CTGCCGGGCCTGCCACTGCCCTGACGCCGGTGGAGAGCTCATCTGCTACCAGCTCCCCGGTTGCCAC
	GGGAACTTCTCAGATGCCGAGCAGQGTGACCCCGAGCGACACTACGAAGACCCCTACAGCTATGACC
	AGGAGGTGGCCGAGGTCGAAGCAGCAACAGCCCTGGGGGGTGAGGTCCAGGGGGGTGCAGTCCACGC
	AGGCGCAGGGGGCCCCCCAGCTGCTCTGGGAGGTGGGAGTCAGCCACTGTCCACCATCCAGGCACCC
	CCCTGGCCAGCTGTCCTCCCCAGCCCCACAGCGCCTGCTGCCCTGGGTCCCCCAGCCCCAGTGCAGG
	CCAAAGCTAGGAGAGTGACCGAGGACAGTGAGGAGGAAGAAGAGGAGGAGGAGGAGAGAGAGGAAAT
	GGCTGTCACTGAGCAGCTGGCAGCAGGTGGCCACAGGGGGCTGGATCGGCTGCCCACTACAGCCCCA
	GCTGGACCCACTCTTCCTATCCAGGAGGAGAGGGCAGAAGCTGGGGCAAGGGCAGAAGCTGGGGCAA
	GGCCTGAAGAGAACCTCATCCTGGATGCCCAAGCCACGTCCCGCAGCACTCCGCCGGAGGGCGTGAC
	GCATGCACCGAGCCTGGGCAAGGCTGCTCTCGTCCCAACTCAGGCCGTGCCTGGCTCTCCCAGGCAC
	CCAGTCAAGCCCAGCCCCCACAACATCCTGTCCACATCACTGCCTGATGCAGCCTGGATCCCACCCA
	CCCGAGAACTGCCCAGGAAGCCGCAAGTTCTGCCCCATTCCCACGTGGAGGAGGACACAGACCCCAA
	CTCTGTCCATTCTATCCCCAGAAGTACCCCTGAAGGCTCCACCAAGGACCTGATCGACACTTGCTGC
	GCACCCGGACAGCAGTGGGCCATTGACAATGACGAGTGCCTGGAGATCCCTGAGAGTCGCACTGACG
	ACAACGTCTGCACGACAGCCCAGAGCCACTGCTGTGTCTCCTACTTGCAGGAGAAGAGCTGCATGGC
	CGGCGTCCTGGGAGCCAAGCAGGGTGAGACCTGTGGGGCTGAGGACAACGACAGCTGCGGCATCTCC
	CTGTACAAGCAATGCTGTGACTGCTGTCGCCTCGGCCTCCGCGTGCGGGCCGAGGGCCAGTCGTGTG
	AGTCCAATCCTAACCTGGGCTATCCCTGCAATCATGTCATGCTCTCCTGCTGTGAGGGTGAAGAGCC
	TCTCATAGTACCTGAGGTTCGCCGACCTCCAGAGCCCGCAGCTGCACCACGGAGAGTTTCAGAGGCA
	GAGATGCCGGGCCGAGAGGCCCTGTCACTGGGCACAGAGGCCGAGCTGCCCAACAGCCTGCCGGGCG
	ATGACCAGGATGAGTGCCTTCTCCTCCCGGGAGAGCTGTGCCAGCACCTTTGCATCAATACTGTGGG
	TTCTTACCACTGTGCCTGCTTTCCTGGCTTCTCACTGCAGGACGATGGCCGCACTTGCCGCCCAGAG
	GGTCACCCTCCACAGCCCGAAGCCCCACAGGAGCCTGCACTGAAGTCAGAATTTTCCCACGTGGCCT
	CTAACACCATCCCGCTGCCACTGCCGCAGCCCAATACCTGCAAAGACAATGGACCCTGCAAGCAGGT
	GTGCAGCACTGTTGGGGGCTCAGCCATATGCTCCTGTTTTCCCGGCTATGCCATCATGCCGGATGGC
	GTGTCCTGTGAAGACATCAACGAGTGTGTGACGGACCTGCACACGTGCAGCCGGGGCGAGCACTGTG
	TGAACACACTGGGCTCCTTCCACTGCTACAAGGCACTCACCTGTGAGCCAGGCTATGCCCTCAAGGA
	TGGCGAGTGCGAAGACGTGGATGAGTGTGCGATGGGCACGCACACCTGCCAGCCCGGCTTCTTGTGC
	CAGAACACCAAGGGCTCCTTCTACTGCCAGGCCAGOCAGCGCTGCATGGATGGCTTCCTGCAGGATC
	CTGAACGCAACTGTGTGGACATCAACGAGTGCACGTCACTCTCCGAGCCATGTCGGCCAGGCTTCAG
	CTGCATCAACACGGTGGGCTCCTACACGTGCCAGAGGAACCCGCTGATCTGCGCGCGCGGCTACCAC
	GCCAGCGATGATGGGGCCAAGTGTGTGGACGTGAATGAGTGTGAGACAGGTGTGCACCGCTGCGGTG
	AGGGCCAAGTGTGCCACAACCTCCCTGGCTCCTACCGCTGTGACTGCAAAGCCGGCTTTCAGCGCGA
	TGCCTTCGGCCAGCGCTGCAQCCAGGAGTGTGCCAACATCTATGGCTCCTACCAGTGCTACTGCCGC
	CAGGGCTACCAGCTGGCTGAGGATGGGCACACCTGCACAGACATCQACGAGTGTGCTCAAGGCGCCG
	GCATCCTCTGCACCTTCCGCTGTCTCAACGTGCCAGGGAGCTACCAGTGTGCATGCCCTGAQCAGGG
	CTACACCATGACGGCCAACGGGAGGTCCTGCAAGGACGTGGATGAGTGTGCACTGGCTACCCACAAC
	TGTTCCGAGGCTGAGACCTGCCACAACATCCAGGGTAGCTTCCGCTGCCTGCQCTTCGAGTGTCCTC
	CCAACTATGTCCAAGTCTCCAAAACGAAGTGCGAGCGCACCACGTGCCATGACTTCCTGGAGTGCCA
	GAACTCGCCAGCGCGCATCACGCACTACCAGCTCAACTTCCAGACGGGCCTCCTCGTGCCTGCGCAT
	ATCTTCCGCATTGGCCCCGCGCCAGCCTTCACGGGGGACACCATCGCCCTGAACATCATCAAGCGCA
	ATGAGGAGGGCTACTTTGGCACGCGCAGGCTCAATGCCTACACGGGTGTGGTCTACCTGCAGCGGGC
	CGTGCTGGAGCCCCGGGACTTTGCCCTGGACGTGGAGATGAAGCTCTGGAGGCAGGGCTCCGTCACC
	ACCTTCCTGGCCAAGATGCACATCTTCTTCACCACCTTTGCCCTGTGAGGTGCCAGCACCGGCCACC
	TGCGGGTGTGGCGCAGCCAGGGCTCACACTGCGTGCGACGGACTGCGTCACTATTGTOGTTTTTACT
	ATAACTTTGTAAATTAACTTAATTTTGCTGACTTGACTCCTGTGGCTTCTGGACCCCTCCTCTGCCC
	CGCAGOAGGAAGTTCCACGGCACGTCGTGCGTTCCCATGTAGGCACCAAGTGGAAGCTTGCACGGTG
	GGCCACGGCCGTGGCGGGTGCCCTGTCGGTGAGGCTGGGTGATGACCTGAGGACCAGAGACACGCGA
	CCATGTTGGGGCTCTTGCACTCCTCTGGATGACCCGTCCCCAAACGTTGACATTCCATTTCATGTTC
	CACTGTGATTAACTTCTTTTCTTTTTTAAAAAATCATTTTAAAGTTTTTTGTTTAACTATAAAGTAG
	TACATGTACATTATATAAAAAAAAAGTTCAACTAGTATGAAAGCGTTATAAAGTAACAGAGGAAAAC
	GCCTCTTGGTCCCTTTAAAAAAAAAAA
	ORF Start: ATG at 70		ORF Stop: TGA at 3463
	SEQ ID NO:8	1131 aa	MW at 120816.8 kD
NOV2b,	MVLLWEPAGAWLALGLALALGPSVAAAAPRQDCTGVECPPLENCIEEALEPGACCATCVQQGCACEG
CG103827-02
Protein	YQYYDCLQGGFVRGRVPAGQSYFVDFGSTECSCPPGGGKISCQFMLCPELPPNCIEAVVVADSCPQC
Sequence
	GQVGCVHAGHEYAAGHTVHLPPCRACHCPDAGGELICYQLPGCHGNFSDAEEGDPERHYEDPYSYDQ
	EVAEVEAATALCGEVQAGAVQAGAGGPPAALGGGSQPLSTIQAPPWPAVLPRPTAAAALGPPAPVQA
	KARRVTEDSEEEEEEEEEREEMAVTEQLAAGGHRGLDGLPTTAPAGPSLPIQEERAEAGARAEAGAR
	PEENLILDAQATSRSTGPEGVTHAPSLGKAALVPTQAVPGSPRDPVKPSPHNILSTSLPDAAWIPPT
	REVPRKPQVLPHSHVEEDTDPNSVHSIPRSSPEGSTKDLIETCCAACQQWAIDNDECLEIPESGTED
	NVCRTAQRHCCVSYLQEKSCMAGVLGAKEGETCGAEDNDSCGISLYKQCCDCCGLGLRVRAEGQSCE
	SNPNLGYPCNHVNLSCCEGEEPLIVPEVRRPPEPAAAPRRVSEAEMAGREALSLGTEAELPNSLPGD
	DQDECLLLPGELCQHLCINTVGSYHCACFPGFSLQDDGRTCRPEGHPPQPEAPQEPALKSEFSQVAS
	NTIPLPLPQPNTCKDNGPCKQVCSTVGQSAICSCFPGYAIMADGVSCEDINECVTDLHTCSRGEHCV
	NTLGSFHCYKALTCEPGYALKDGECEDVDECAMGTHTCQPGFLCQNTKGSPYCQARQRCMDCFLQDP
	EGNCVDINECTSLSEPCRPGFSCINTVGSYTCQRNPLICARGYHASDDGAKCVDVNECETGVHRCGE
	GQVCHNLPGSYRCDCKACFQRDAFGQRCSQECANIYGSYQCYCRQQYQLAEDGHTCTDIDECAQGAG
	ILCTPRCLNVPGSYQCACPEQGYTMTANGRSCKDVDECALGTHNCSEAETCHNIQGSFRCLRFECPP
	NYVQVSKTKCERTTCHDFLECQNSPARITHYQLNFQTGLLVPAHIFRIGPAPAFTGDTIALNIIKGN
	EEGYFGTRRLNAYTGVVYLQRAVLEPRDFALDVEMKLWRQGSVTTFLAKMHIFFTTFAL
	SEQ ID NO:9	3240 bp
NOV2c,	TCGCGGCCGCCGAGCGCAGTGCCCCGCQGGTCTTACAGGAGAGGGGACCGTCCTGGGCTGGCCTCGAC
CG103827-03
DNA Sequence	CATGGTGCTGCTCTGGGAGCCTGCAGGAGCCTGGCTTGCTCTGGGCCTGGCCCTGGCCCTGGGCCCCA
	GCGTGGCCGCAGCTGCCCCTCGGCAGGACTGCACGGGCGTGGAGTGCCCGCCGCTGGAGAACTGCATT
	GAGGAGGCGCTGGAGCCGGGTGCCTGCTCTGCCACGTGTGTGCAGCAGGGCTGCGCCTGCGAGGGCTA
	CCAGTACTATGACTGCCTACAGGGTGCCTTCGTGCGCGGCCGCGTGCCCGCCGGTCAGTCCTATTTTG
	TGGACTTCGGGAGCACTGAGTGCTCCTGCCCACCAGGCGGCGGCAAQATCAGCTGCCAGTTCATGCTC
	TGCCCCGAGCTGCCCCCCAACTGCATCGAGGCTGTAGTGGTGGCTGACAGCTGCCCACAGTGCGGCCA
	GGTGGGCTGCGTCCACGCGCGCCACGAGTACGCCGCTGGCCACACTGTTCACCTGCCCCCCTGCCGGG
	CCTCCCACTGCCCTGACGCCQGTGGAGAGCTCATCTGCTACCAGCTCCCCGGTTGCCACGGGAACTTC
	TCAGATGCCCACGAGCGTGACCCCGAGCGACACTACGAAGACCCCTACAGCTATGACCAGGAGGTGGC
	CGAGGTGGAAGCAGCAACAGCCCTGGGGGGTCAGGTCCACGCGGGTGCAGTCCAGGCAGGCGCAGGGG
	GCCCCCCAGCTGCTCTGCGAGGTGGGAGTCAGCCACTGTCCACCATCCAGGCACCCCCCTGGCCACCT
	GTCCTCCCCACGCCCACAGCQGCTGCTGCCCTCGGTCCCCCAGCCCCAGTGCAGGCCAAAGCTAGGAG
	AGTGACCGAGGACAGTGAGGAGGAAGAAGAGGAGGAGGACGAGAGAGACGAAATGGCTGTCACTGAGC
	AGCTGGCAGCACGTGGCCACAGGCGGCTGGATGGGCTGCCCACTACAGCCCCAGCTGGACCCAGTCTT
	CCTATCCAGGAGGAGAGGGCAGAAGCTGGGGCAAGCGCAGAAGCTGGGGCAAGGCCTGAAGAGAACCT
	CATCCTGGATGCCCAAGCCACGTCCCGCAOCACTGGGCCGQAGCGCGTGACGCATGCACCGAGCCTGG
	GCAAGGCTGCTCTCGTCCCAACTCAGGCCGTGCCTGGCTCTCCCAGGGACCCAGTCAACCCCAGCCCC
	CACAACATCCTGTCCACATCACTGCCTGATGCAGCCTGGATCCCACCCACCCGAGAAGTGCCCAGGAA
	GCCGCAAGTTCTGCCCCATTCCCACGTGGAGGAGGACACAGACCCCAACTCTGTCCATTCTATCCCCA
	GAAGTAGCCCTGAAGGCTCCACCAAGGACCTGATCGAGACTTGCTGCGCAGCCGGACAGCAGTGGGCC
	ATTGACAATCACGAGTGCCTGGAGATCCCTGAGAGTGGCACTQAGGACAACGTCTGCACGACAGCCCA
	GAGGCACTGCTGTGTCTCCTACTTGCAGGAGAAGAGCTGCATGGCCGGCGTCCTGGGAGCCAAGGAGG
	GTGAGACCTGTGGGGCTGAGGACAACGACAGCTGCGGCATCTCCCTGTACAAGCAATGCTGTGACTGC
	TGTGGCCTGGGCCTCCGCGTGCGCGCCGAGGGCCAGTCGTGTGAGTCCAATCCTAACCTGGGCTATCC
	CTGCAATCATGTCATGCTCTCCTGCTGTGAGGGTGAAGAGCCTCTCATAGTACCTGAGGTTCGCCGAC
	CTCCAGAGCCCGCAGCTGCACCACGGAGAGTTTCAGAGGCAGACATGGCGGGCCGAGAGGCCCTGTCA
	CTGCGCACAGAGGCCGAGCTGCCGAACAGCCTGCCGGGCGATGACCAGCATGAGTGCCTTCTCCTCCC
	GGGAGAGCTGTGCCAGCACCTTTGCATCAATACTGTGGGTTCTTACCACTGTGCCTGCTTTCCTGGCT
	TCTCACTGCAGGACGATGGCCGCACTTGCCGCCCAGAGGGTCACCCTCCACAGCCGGAAGCCCCACAG
	GAGCCTGCACTGAAQTCAGAATTTTCCCAGGTGGCCTCTAACACCATCCCGCTGCCACTGCCGCAGCC
	CAATACCTGCAAAGACAATCGACCCTGCAAGCAGGTGTGCAGCACTGTTGGGGGCTCAGCCATATGCT
	CCTGTTTTCCCGGCTATCCCATCATGGCGGATGGCGTGTCCTGTGAAGACATCAACGAGTGTGTGACG
	GACCTGCACACGTGCAGCCGGGGCGAGCACTGTGTGAACACACTGCGCTCCTTCCACTGCTACAAGGC
	ACTCACCTGTGAGCCAGGCTATGCCCTCAAGGATGGCGAGTGCGAAGACGTGGATGAGTGTGCGATGG
	GCACGCACACCTGCCAGCCGGGCTTCTTGTGCCAGAACACCAAGGGCTCCTTCTACTGCCACGCCAGG
	CAGCGCTGCATGGATGGCTTCCTGCAGGATCCTGAAGGCAACTGTGTCGACATCAACGAGTGCACGTC
	ACTGTCCGAGCCATGTCGGCCAGGCTTCAGCTGCATCAACACGGTGGGCTCCTACACGTGCCAGAGGA
	ACCCGCTGATCTGCGCGCGCGGCTACCACGCCAGCGATGATGGCGCCAAGTGTGTGGACGTGAATGAG
	TGTGAGACAGGTGTGCACCGCTGCGGTGAGGGCCAAGTGTGCCACAACCTCCCTGGCTCCTACCGCTG
	TGACTGCAAAGCCGGCTTTCAGCGGGATGCCTTCGGCCGGGGCTGCATCGACGTGAATGAGTGCTGCG
	CCTCGCCAGGCCGCCTGTGCCAGCACACGTGTGAGAACACACTCGGCTCCTACCGCTGTTCCTGCGCC
	TCCGGGTTCCTGCTAGCAGCGGACGGCAAGCGCTGTGAAGACATCGACGAGTGTGCTCAAGGCGCCGG
	CATCCTCTGCACCTTCCGCTGTCTCAACGTGCCAGGGAGCTACCAGTGTGCATGCCCTGAGCAGGGCT
	ACACCATGACGGCCAACGCGAGGTCCTGCAAGGACGTGGATGAGTGTGCACTGGGTACCCACAACTGT
	TCCGAGGCTGAGACCTGCCACAACATCCAGGGTAGCTTCCGCTGCCTGCGCTTCGAGTGTCCTCCCAA
	CTATGTCCAAGTCTCCAAAACGAAGTGCGTTCCCACGCAGGCACCAAGTGGAAGCTTGCACGGTCGGC
	CACGGCCGTGGCGGGTGCCCTGTGGGTGAGGCTGGGTGATGACC
	ORF Start: ATG at 70		ORF Stop: TGA at 3223
	SEQ ID NO:10	1051 aa	MW at 111164.9 kD
NOV2c,	MVLLWEPAGAWLALGLALALGPSVAAAAPRQDCTGVECPPLENCIEEALEPGACCATCVQQGCACEGY
CG103827-03
Protein	QYYDCLQGGFVRGRVPAGQSYFVDFGSTECSCPPGGGKISCQFMLCPELPPNCIEAVVVADSCPQCGQ
Sequence
	VGCVHAGHEYAAGHTVHLPPCRACHCPDAGGELICYQLPGCHGNFSDAEEGDPERHYEDPYSYDQEVA
	EVEAATALGGEVQAGAVQAGAGGPPAALGGGSQPLSTTQAPPWPAVLPRPTAAAALGPPAPVQAKARR
	VTEDSEEEEEEEEEREEMAVTEQLAACGHRGLDGLPTTAPAGPSLPIQEERAEAGARAEAGARPEENL
	ILDAQATSRSTGPEGVTHAPSLQKAALVPTQAVPGSPRDPVKPSPHNILSTSLPDAAWIPPTREVPRK
	PQVLPHSHVEEDTDPNSVHSIPRSSPEGSTKDLIETCCAAGQQWAIDNDECLEIPESGTEDNVCRTAQ
	RHCCVSYLQEKSCMAGVLGAKEGETCGAEDNDSCGISLYKQCCDCCGLGLRVPAEGQSCESNPNLGYP
	CNHVNLSCCEGEEPLIVPEVRRPPEPAAAPRRVSEAEMAGREALSLGTEAELPNSLPGDDQDECLLLP
	GELCQHLCINTVGSYHCACFPGFSLQDDGRTCRPEGHPPQPEAPQEPALKSEFSQVASNTIPLPLPQP
	NTCKDNGPCKQVCSTVQGSAICSCFPGYAIMADGVSCEDINECVTDLHTCSRGEHCVNTLGSFHCYKA
	LTCEPGYALKDGECEDVDECAMGTHTCQPGFLCQNTKGSFYCQARQRCMDGFLQDPEGNCVDINECTS
	LSEPCRPQFSCINTVGSYTCQRNPLICARGYHASDDGAKCVDVNECETGVHRCGEGQVCXNLPGSYRC
	DCKAGFQRDAFGRGCIDVNECWASPGRLCQHTCENTLGSYRCSCASGFLLAADGKRCEDIDECAQGAG
	ILCTFRCLNVPGSYQCACPEQGYTMTANGRSCKDVDECALGTHNCSEAETCHNIQGSFRCLRFECPPN
	YVQVSKTKCVPTQAPSGSLHGGPRPWRVPCG
	SEQ ID NO:11	4022 bp
NOV2d,	TCGCGGCCGCCGAGCGCAGTGCCCCGCGGGTCTTACAGGAGAGGGGACCGTCCTGGGCTGGCCTGGA
CG103827-04
DNA Sequence	CCATGGTGCTGCTCTGGGAGCCTGCAGGAGCCTGGCTTGCTCTGGGCCTGGCCCTGGCCCTGGGCCC
	CAQCGTGGCCGCAGCTGCCCCTCGGCACGACTGCACGGGCGTGGAGTGCCCGCCGCTGGAGAACTGC
	ATTGACGAGGCGCTGGAGCCGGGTGCCTGCTGTGCCACGTGTGTCCAGCAGGGCTGCGCCTGCGAGG
	GCTACCAGTACTATGACTGCCTACACGGTGGCTTCGTGCCCGGCCCCGTGCCCGCCGGTCAGTCCTA
	TTTTGTGGACTTCGGGAGCACTGAGTGCTCCTGCCCACCACGCCGCGGCAAGATCAGCTGCCAGTTC
	ATGCTGTGCCCGGAGCTGCCGCCCAACTGCATCQAGCCTGTAGTGGTGCCTGACAGCTGCCCACAGT
	GCGGCCAGGTGGGCTGCGTCCACGCGGGCCACGAGTACGCCGCTGGCCACACTGTTCACCTGCCGCC
	CTGCCGGGCCTGCCACTGCCCTGACGCCGQTGGAGAGCTCATCTGCTACCAGCTCCCCGGTTGCCAC
	GGGAACTTCTCAGATGCCGAGGAGCGTGACCCCGAGCGACACTACGAAGACCCCTACAGCTATGACC
	AGGAGGTGGCCGAGGTGGAAGCAGCAACAGCCCTGGGGGGTGAGGTCCAGGCGGGTGCAGTCCAGGC
	AGGCGCAQGGGGCCCCCCAGCTGCTCTCGGAGGTGGGAGTCAGCCACTGTCCACCATCCAGGCACCC
	CCCTGGCCAGCTGTCCTCCCCAGGCCCACAGCCGCTGCTGCCCTGGGTCCCCCAGCCCCAGTCCAGG
	CCAAAGCTAGGAGAGTGACCGAGGACAGTGAGGAGGAAGAAGAGGAGGAGGAGGAGAGAGAGGAAAT
	GGCTGTCACTGAGCAGCTGGCAGCAGGTGGCCACAGGGGGCTGGATGGGCTGCCCACTACAGCCCCA
	GCTGGACCCAGTCTTCCTATCCAGGAGGAGAGGGCAGAAGCTGGGGCAAGGGCAGAAGCTGGGGCAA
	GGCCTGAAGAGAACCTCATCCTGGATGCCCAAGCCACGTCCCGCAGCACTGGGCCGGAGGGCGTGAC
	GCATGCACCGAGCCTGGGCAAGGCTGCTCTCGTCCCAACTCAGGCCGTGCCTGGCTCTCCCAGGGAC
	CCAGTCAAGCCCAGCCCCCACAACATCCTGTCCACATCACTQCCTGATGCAGCCTGGATCCCACCCA
	CCCGAGAAGTGCCCAGGAAGCCGCAAGTTCTGCCCCATTCCCACGTGGAGGAGGACACAGACCCCAA
	CTCTGTCCATTCTATCCCCAGAAGTAGCCCTGAAGGCTCCACCAAGGACCTGATCGAGACTTGCTGC
	GCAGCCGGACAGCAGTGGGCCATTGACAATGACGAGTGCCTGGAGATCCCTGAGAGTCGCACTGAGG
	ACAACGTCTGCAGGACAGCCCAGAGGCACTGCTGTGTCTCCTACTTGCAGCAGAAGAGCTGCATGGC
	CGGCGTCCTGGGAGCCAAGGAGCGTGAGACCTGTGGGGCTGAQGACAACGACAGCTGCCGCATCTCC
	CTGTACAAGCAATGCTQTGACTGCTGTGGCCTGGGCCTCCGCGTGCGGGCCGAGCGCCAGTCGTGTG
	AGTCCAATCCTAACCTGGGCTATCCCTGCAATCATGTCATGCTCTCCTGCTGTGAGCGTGAAGAGCC
	TCTCATAGTACCTGAOGTTCGCCGACCTCCAGAGCCCGCAGCTGCACCACGGAGAGTTTCACAGGCA
	GAGATGGCGGGCCGAGAGGCCCTGTCACTGGGCACAGACGCCGACCTGCCGAACAGCCTGCCGGGCG
	ATGACCAGGATGAGTGCCTTCTCCTCCCGGGAGAGCTGTGCCAGCACCTTTGCATCAATACTGTCGG
	TTCTTACCACTGTGCCTGCTTTCCTGGCTTCTCACTGCAGGACGATGGCCGCACTTGCCGCCCAGAG
	GGTCACCCTCCACAGCCGGAAGCCCCACAGGAGCCTGCACTGAAGTCAGAATTTTCCCAGGTGGCCT
	CTAACACCATCCCGCTGCCACTGCCGCAGCCCAATACCTGCAAAGACAATGGACCCTGCAAGCAGGT
	GTGCAGCACTGTTGGGGGCTCAGCCATATGCTCCTGTTTTCCCGGCTATGCCATCATGGCGGATGGC
	GTGTCCTGTGAAGACATCAACGAGTGTGTGACGGACCTCCACACGTGCAGCCGGGGCGAGCACTGTG
	TGAACACACTGGGCTCCTTCCACTGCTACAAGGCACTCACCTGTGAGCCAGCCTATGCCCTCAACGA
	TGGCGAGTGCGAAGACGTGGATGAGTQTGCGATGGGCACGCACACCTGCCAGCCGGGCTTCTTGTQC
	CAGAACACCAACGGCTCCTTCTACTGCCAGGCCAGGCAGCGCTGCATGGATGGCTTCCTGCAGGATC
	CTGAAGGCAACTGTGTGGACATCAACGAGTGCACGTCACTGTCCGAGCCATGTCGGCCAGGCTTCAG
	CTGCATCAACACGGTGGGCTCCTACACGTGCCAGAGGAACCCGCTGATCTGCGCGCGCGGCTACCAC
	GCCAGCGATGATGGGGCCAAGTGTGTGGACGTGAATGAGTGTGAGACACGTGTGCACCGCTGCGGTG
	AGGGCCAAGTGTCCCACAACCTCCCTGGCTCCTACCGCTGTGACTGCAAAGCCGCCTTTCAGCGCGA
	TGCCTTCGGCCGGGGCTGCATCGACGTGAATGAGTGCTGGGCCTCGCCAGGCCGCCTGTGCCAGCAC
	ACGTGTGAGAACACACTCGGCTCCTACCGCTGTTCCTGCGCCTCCGGGTTCCTGCTAGCAGCGGACG
	GCAAGCGCTGTGAAGACATCGACGAGTGTGCTCAAGGCGCCGGCATCCTCTGCACCTTCCGCTGTCT
	CAACGTGCCAGGQAGCTACCAGTGTCCATGCCCTGAGCAGGGCTACACCATGACGGCCAACGGGAGG
	TCCTGCAACGACGTGGATGAGTGTGCACTGGGTACCCACAACTGTTCCGAGGCTGAGACCTGCCACA
	ACATCCAGGGTAGCTTCCGCTGCCTGCGCTTCGAGTGTCCTCCCAACTATGTCCAAGTCTCCAAAAC
	GAAGTGCGAQCGCACCACGTGCCATGACTTCCTCGAGTGCCAGAACTCGCCAGCCCGCATCACGCAC
	TACCAGCTCAACTTCCAGACGGGCCTCCTGGTGCCTGCGCATATCTTCCGCATTGGCCCCGCGCCAG
	CCTTCACGGGGGACACCATCGCCCTGAACATCATCAAGGGCAATGAGGACGGCTACTTTGGCACGCG
	CAGGCTCAATGCCTACACGGGTGTGGTCTACCTGCAGCGGGCCGTGCTGGAGCCCCCGGACTTTGCC
	CTGGACGTGGAGATGAAGCTCTGGAGGCAGGGCTCCGTCACCACCTTCCTGGCCAAGATGCACATCT
	TCTTCACCACCTTTGCCCTGTGAGGTGCCAGCACGCGCCACCTGCGGGTGTGGCQCAGCCAGGGCTC
	ACACTGCGTGGGAGGCACTGGGTCACTATTGTGGTTTTTACTATAACTTTGTAAATTAACTTAATTT
	TGCTGACTTGACTCCTGTGGCTTCTGGACCCCTCCTCTGCCCCGCAGGAGGAAQTTCCACGGCAGGT
	GGTGCGTTCCCATGTAGGCACCAAGTGGAAGCTTGCACGGTGGGCCACGGCCGTGGCGGGTGCCCTG
	TGGGTGAGGCTGGGTGATGACCTGAGGACCAGAGACACGCGACCATGTTGGGGCTCTTGGACTCCTC
	TGGATGACCCGTCCCCAAACGTTGACATTCCATTTCATGTTCCACTGTGATTAACTTCTTTTCTTTT
	TTAAAAAATCATTTTAAAGTTTTTTGTTTAACTATAAAGTAGTACATGTACATTATATAAAAAAAAA
	GTTCAACTAGTATGAAAGGGTTATAAAGTAACAGAGGAAAACGCCTCTTGGTCCCTTTAAAAAAAAA
	AA
	ORF Start: ATG at 70		ORF Stop: TGA at 3505
	SEQ ID NO: 12	1145 aa	MW at 122119.4 kD
NOV2d,	MVLLWEPAGAWLALGLALALGPSVAAAAPRQDCTGVECPPLENCIEEALEPGACCATCVQQGCACEG
CG103827-04
Protein	YQYYDCLQGGFVRGRVPAGQSYPVDFGSTECSCPPCGGKISCQFMLCPELPPNCIEAVVVADSCPQC
Sequence
	GQVGCVHAGHEYAAGHTVHLPPCRACHCPDAGGELICYQLPGCHGNFSDAEEGDPERHYEDPYSYDQ
	EVAEVEAATALCGEVQAGAVQAGAGGPPAALGCGSQPLSTIQAPPWPAVLPRPTAAAALGPPAPVQA
	KARRVTEDSEEEEEEEEEREEMAVTEQLAAGGHRGLDGLPTTAPAGPSLPIQEERAEAGARAEAGAR
	PEENLILDAQATSRSTGPEGVTHAPSLGKAALVPTQAVPGSPRDPVKPSPHNILSTSLPDAAWIPPT
	REVPRKPQVLPHSHVEEDTDPNSVHSIPRSSPEGSTKDLIETCCAAGQQWAIDNDECLEIPESGTED
	NVCRTAQRHCCVSYLQEKSCMAGVLGAKEGETCGAEDNDSCQISLYKQCCDCCGLGLRVRAEGQSCE
	SNPNLGYPCNHVMLSCCEGEEPLIVPEVRRPPEPAAAPRRVSEAEMAGREALSLGTEAELPNSLPGD
	DQDECLLLPGELCQHLCINTVGSYHCACPPGFSLQDDGRTCRPECHPPQPEAPQEPALKSEFSQVAS
	NTIPLPLPQPNTCKDNGPCKQVCSTVGGSAICSCFPGYAIMADGVSCEDINECVTDLHTCSRGEHCV
	NTLGSFHCYKALTCEPGYALKDGECEDVDECAMGTHTCQPGFLCQNTKGSFYCQARQRCMDGFLQDP
	EGNCVDINECTSLSEPCRPGFSCINTVGSYTCQRNPLICARGYHASDDGAKCVDVNECETGVHRCGE
	GQVCHNLPGSYRCDCKAGFQRDAFGRGCIDVNECWASPGRLCQHTCENTLGSYRCSCASGFLLAADG
	KRCEDIDECAQGAGILCTFRCLNVPGSYQCACPEQGYTMTANGRSCKDVDECALQTHNCSEAETCHN
	IQGSFRCLRFECPPNYVQVSKTKCERTTCHDFLECQNSPARITHYQLNFQTGLLVPAHIFRIGPAPA
	FTGDTIALNIIKGNEEGYFGTRRLNAYTGVVYLQRAVLEPRDFALDVEMKLWRQGSVTTFLAKMHIF
	FTTFAL

[0373] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 2B.

TABLE 2B
Comparison of NOV2a against NOV2b through NOV2d.
		NOV2a Residues/	Identities/Similarities
	Protein Sequence	Match Residues	for the Matched Region
	NOV2b	1 . . . 1184	1131/1184 (95%)
		1 . . . 1131	1131/1184 (95%)
	NOV2c	1 . . . 1071	1030/1071 (96%)
		1 . . . 1032	1030/1071 (96%)
	NOV2d	1 . . . 1184	1145/1184 (96%)
		1 . . . 1145	1145/1184 (96%)

[0374] Further analysis of the NOV2a protein yielded the following properties shown in Table 2C.

TABLE 2C
Protein Sequence Properties NOV2a
SignalP
analysis:	Cleavage site between residues 28 and 29
PSORT II	PSG:	a new signal peptide prediction method
analysis:		N-region: length 6; pos. chg 0; neg. chg 1
		H-region: length 23; peak value 0.00
		PSG score: −4.40
	GvH:	von Heijne's method for signal seq. recognition
		GvH score (threshold: −2.1): −0.40
		possible cleavage site: between 25 and 26
	>>> Seems to have no N-terminal signal peptide
	ALOM:	Klein et al's method for TM region allocation
		Init position for calculation: 1
		Tentative number of TMS(s) for the threshold 0.5: 1
		Number of TMS(s) for threshold 0.5: 1
		INTEGRAL Likelihood = −3.03
		Transmembrane 12-28
		PERIPHERAL Likelihood = 2.01 (at 1168)
		ALOM score: −3.03 (number of TMSs: 1)
	MTOP:	Prediction of membrane topology (Hartmann et al.)
		Center position for calculation: 19
		Charge difference: −2.0 C(−2.0) − N(0.0)
		N >= C: N-terminal side will be inside
	>>> membrane topology: type 2 (cytoplasmic tail 1 to 12)
	MITDISC: discrimination of mitochondrial targeting seq
		R content: 1	Hyd Moment (75): 4.70
		Hyd Moment (95): 5.95	G content: 3
		D/E content: 2	S/T content: 1
		Score: −7.47
	Gavel:	prediction of cleavage sites for mitochondrial preseq
		R-2 motif at 40 PRQ|DC
	NUCDISC: discrimination of nuclear localization signals
		pat4: none
		pat7: none
		bipartite: none
		content of basic residues: 6.8%
		NLS Score: −0.47
	KDEL: ER retention motif in the C-terminus: none
	ER Membrane Retention Signals: none
	SKL: peroxisomal targeting signal in the C-terminus: none
	PTS2: 2nd peroxisomal targeting signal: none
	VAC: possible vacuolar targeting motif: none
	RNA-binding motif: none
	Actinin-type actin-binding motif:
		type 1: none
		type 2: none
	NMYR:	N-myristoylation pattern: none
	Prenylation motif: none
	memYQRL: transport motif from cell surface to Golgi: none
	Tyrosines in the tail: none
	Dileucine motif in the tail: found
		LL at 3
	checking 63 PROSITE DNA binding motifs: none
	checking 71 PROSITE ribosomal protein motifs: none
	checking 33 PROSITE prokaryotic DNA binding motifs: none
	NNCN:	Reinhardt's method for Cytoplasmic/Nuclear
		discrimination
		Prediction: nuclear
		Reliability: 76.7
	COIL:	Lupas's algorithm to detect coiled-coil regions
		total: 0 residues
	------------------------------
	Final Results (k = 9/23):
		47.8%: nuclear
		21.7%: mitochondrial
		13.0%: cytoplasmic
		4.3%: vacuolar
		4.3%: plasma membrane
		4.3%: extracellular, including cell wall
		4.3%: peroxisomal
	>> prediction for CG103827-01 is nuc (k = 23)

[0375] 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
Geneseq	Protein/Organism/Length	NOV2a Residues/	Identities/Similarities	Expect
Identifier	[Patent #, Date]	Match Residues	for the Matched Region	Value
ABP63045	Human polypeptide SEQ ID	1 . . . 1184	1183/1231 (96%)	0.0
	NO 482 - Homo sapiens,	1 . . . 1231	1183/1231 (96%)
	1231 aa.
	[WO200218424-A2,
	07-MAR-2002]
AAM40146	Human polypeptide SEQ ID	549 . . . 1184	635/636 (99%)	0.0
	NO 3291 - Homo sapiens,	1 . . . 636	636/636 (99%)
	636 aa. [WO200153312-A1,
	26-JUL-2001]
AAM79191	Human protein SEQ ID NO	582 . . . 1184	602/603 (99%)	0.0
	1853 - Homo sapiens, 603	1 . . . 603	602/603 (99%)
	aa. [WO200157190-A2,
	09-AUG-2001]
AAM41932	Human polypeptide SEQ ID	656 . . . 1184	528/576 (91%)	0.0
	NO 6863 - Homo sapiens,	1 . . . 576	528/576 (91%)
	576 aa. [WO200153312-A1,
	26-JUL-2001]
AAM80175	Human protein SEQ ID NO	656 . . . 1184	528/576 (91%)	0.0
	3821 - Homo sapiens, 576	1 . . . 576	528/576 (91%)
	aa. [WO200157190-A2,
	09-AUG-2001]

[0376] 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
Protein		NOV2a Residues/	Identities/Similarities	Expect
Accession Number	Protein/Organism/Length	Match Residues	for the Matched Portion	Value
P98095	Fibulin-2 precursor - Homo	1 . . . 1184	1184/1184 (100%)	0.0
	sapiens (Human), 1184 aa.	1 . . . 1184	1184/1184 (100%)
CAD33510	Sequence 237 from Patent	1 . . . 1184	1183/1231 (96%)	0.0
	WO0218424 - Homo sapiens	1 . . . 1231	1183/1231 (96%)
	(Human), 1231 aa.
AAN05436	Fibulin 2 - Homo sapiens	1 . . . 1184	1183/1231 (96%)	0.0
	(Human), 1231 aa.	1 . . . 1231	1183/1231 (96%)
AAN05435	Fibulin 2 - Homo sapiens	1 . . . 1184	1182/1231 (96%)	0.0
	(Human), 1231 aa.	1 . . . 1231	1182/1231 (96%)
Q99K58	Similar to fibulin 2 - Mus	2 . . . 1183	966/1186 (81%)	0.0
	musculus (Mouse), 1174 aa.	1 . . . 1173	1029/1186 (86%)

[0377] PFam analysis predicts that the NOV2a protein contains the domains shown in the Table 2F.

TABLE 2F
Domain Analysis of NOV2a
			Identities/
		NOV2a	Similarities
	Pfam	Match	for the Matched	Expect
	Domain	Region	Region	Value
	vwc	73..134	20/87 (23%)	0.16
			46/87 (53%)
	vwc	139..189	16/84 (19%)	0.5
			30/84 (36%)
	ANATO	445..480	11/37 (30%)	0.42
			21/37 (57%)
	ANATO	521..553	13/37 (35%)	0.0099
			21/37 (57%)
	EGF	608..644	14/47 (30%)	0.0001
			29/47 (62%)
	EGF	683..717	13/47 (28%)	0.33
			22/47 (47%)
	EGF	862..899	13/47 (28%)	4.1e−05
			27/47 (57%)
	EGF	905..941	16/47 (34%)	1.7e−05
			27/47 (57%)
	TIL	899..947	16/68 (24%)	0.33
			32/68 (47%)
	EGF	947..980	14/47 (30%)	0.0045
			25/47 (53%)
	EGF	986..1023	14/47 (30%)	0.3
			27/47 (57%)

Example 3

[0378] 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:13	2296 bp
NOV3a,	CACCAAGCTTCCCACCATGGTCCCCGACACCGCCTGCGTTCTTCTGCTCACCCTGGCTGCCCTCGGCG
CG105716-09
DNA Sequence	CGTCCCGACAGGGCCAGAGCCCGTTGGGCTCAGACCTGGGCCCGCAGATGCTTCGGGAACTGCACGAA
	ACCAACGCGGCGCTGCAGGACGTGCGGGACCTGCTGCGGCAGCAGGTCAGGGAGATCACGTTCCTGAA
	AAACACGGTGATGGAGTGTGACGCGTGCGGGATGCAGCAGTCAGTACGCACCGGCCTACCCAGCGTGC
	GGCCCCTCCTCCACTGCGCGCCCGGCTTCTGCTTCCCCGGCGTGGCCTGCATCCAGACGGAGAGCCGC
	GCGCCCTGCCGCCCCTGCCCCGCGGGCTTCACGGGCAACGGCTCGCACTGCACCGACGTCAACGAGTG
	CAACGCCCACCCCTGCTTCCCCCGAGTCCGCTGTATCAACACCAGCCCGGGGTTCCGCTGCGAGCCTT
	GCCCGCCGGCGTACAGCGGCCCCACCCACCAGGGCGTGGGGCTGGCTTTCGCCAAGGCCAACAAGCAG
	GTTTGCACCGACATCAACGAGTGTGAGACCGGGCAACATAACTGCGTCCCCAACTCCGTGTGCATCAA
	CACCCGGGGCTCCTTCCAGTGCGGCCCGTGCCAGCCCGGCTTCGTGGGCGACCACGCGTCCGGCTGCC
	AGCGGCGCGCACAQCGCTTCTGCCCCGACGGCTCCCCCAGCGAGTGCCACGAGCATGCAGACTGCGTC
	CTAGAGCGCGATCGCTCGCGGTCGTGCGTGTGTGCCGTTGGCTGGCCCGGCAACCGGATCCTCTQTGQ
	TCGCGACACTGACCTAGACGGCTTCCCGGACGAGAAGCTCCGCTCCCCCGAGCGCCAGTGCCGTAAGG
	ACAACTGTGTQACTGTGCCCAACTCAGGGCAGGAGGATGTGGACCGCGATCGCATCGGAGACGCCTGC
	GATCCGGATGCCGACGGGGACGCGGTCCCCAATGAAAAGCACAACTGCCCGCTGGTGCGGAACCCAGA
	CCAGCGCAACACGGACCAGCACAAGTGGGGCGATGCGTGCGACAACTGCCGGTCCCAGAAGAACGACG
	ACCAAAAGGACACAGACCAGGACGGCCGGGGCGATGCGTCCGACGACGACATCGACCGCGACCGGATC
	CGCAACCAGGCCGACAACTGCCCTAGGGTACCCAACTCAGACCAGAAGGACAGTGATGGCGATGGTAT
	AGGGGATGCCTGTGACAACTGTCCCCAGAAGAGCAACCCGGATCAGGCGGATGTGGACCACGACTTTG
	TGGGACATGCTTGTQACAGCGATCAAGACCAGGATGGAGACCGACATCACGACTCTCGGGACAACTGT
	CCCACGGTGCCTAACAGTGCCCAGGAGGACTCACACCACGATGGCCAGGGTGATGCCTGCGACGACGA
	CGACGACAATGACGGAGTCCCTGACAGTCGGGACAACTGCCGCCTGGTGCCTAACCCCGGCCAGGAGC
	ACGCGGACAGGGACGGCGTGGGCGACGTGTGCCAGGACGACTTTGATGCAGACAAGGTGGTAGACAAG
	ATCGACGTGTGTCCGGAGAACGCTGAAGTCACGCTCACCGACTTCACGGCCTTCCAGACAGTCGTGCT
	GGACCCGGAGGGTGACGCGCAGATTGACCCCAACTGGGTGGTGCTCAACCAGGGAAGGGAGATCGTGC
	AGACAATGAACAGCGACCCAGGCCTGGCTGTGGGTTACACTGCCTTCAATGGCGTGGACTTCGAGGGC
	ACGTTCCATGTGAACACQGTCACGGATGACGACTATGCGGGCTTCATCTTTGGCTACCACGACAGCTC
	CAGCTTCTACGTGGTCATGTGGAAGCAGATGQAGCAAACGTATTGGCAGGCGAACCCCTTCCGTGCTG
	TGGCCGAGCCTCGCATCCAACTCAAGGCTGTGAAGTCTTCCACAGGCCCCGGGGAACAGCTGCGGAAC
	GCTCTGTGGCATACAGGAGACACAGAGTCCCAGGTGCGGCTGCTGTGGAAGGACCCGCGAAACGTCGG
	TTGGAAGGACAAGAAGTCCTATCGTTGGTTCCTGCACCACCGQCCCCAAGTGGGCTACATCAGGGTGC
	GATTCTATGAGGGCCCTGAGCTGGTCGCCGACAGCAACGTCGTCTTGGACACAACCATGCGGGGTGGC
	CGCCTGGGGGTCTTCTGCTTCTCCCAGGAGAACATCATCTGGGCCAACCTGCGTTACCGCTGCAATGA
	CACCATCCCAGAGGACTATGAGACCCATCAGCTGCGGCAAGCCCTCGAGCGC
	ORF Start: ATG at 17		ORF Stop: at 2288
	SEQ ID NO:14	757 aa	MW at 82859.7 kD
NOV3a,	MVPDTACVLLLTLAALGASGQGQSPLGSDLGPQMLRELQETNAALQDVRELLRQQVREITFLKNTVME
CG105716-09
Protein	CDACGMQQSVRTGLPSVRPLLHCAPGFCFPGVACIQTESGARCGPCPAGETGNGSHCTDVNECNAHPC
Sequence
	FPRVRCINTSPGFRCEACPPGYSGPTHQGVGLAFAKANKQVCTDINECETGQHNCVPNSVCINTRGSF
	QCGPCQPGFVGDQASGCORRAQRFCPDGSPSECHEHADCVLERDGSRSCVCAVGWAGNGILCGRDTDL
	DGFPDEKLRCPERQCRKDNCVTVPNSGQEDVDRDGIGDACDPDADGDGVPNEKDNCPLVRNPDQRNTD
	EDKWGDACDNCRSQKNDDQKDTDQDGRGDACDDDIDGDRIRNQADNCPRVPNSDQKDSDGDGIGDACD
	NCPQKSNPDQADVDHDFVGDACDSDQDQDGDGHQDSRDNCPTVPNSAQEDSDHDGQGDACDDDDDNDG
	VPDSRDNCRLVPNPGQEDADRDGVGDVCQDDFDADKVVDKIDVCPENAEVTLTDFRAFQTVVLDPEGD
	AQIDPNWVVMJQGREIVQTMNSDPGLAVGYTAFNGVDPEGTFHVNTVTDDDYAGFIFGYQDSSSFYVV
	MWKQMEQTYWQANPFRAVAEPGIQLKAVKSSTGPGEQLRNALWHTGDTESQVRLLWKDPRNVGWKDKK
	SYRWFLQHRPQVGYIRVRFYEGPELVADSNVVLDTTMRGGRLGVFCFSQENIIWANLRYRCNDTIPED
	YETHQLRQA
	SEQ ID NO:15	2352 bp
NOV3b,	CAGCACCCAGCTCCCCGCCACCGCCATGGTCCCCGACACCGCCTGCGTTCTTCTGCTCACCCTGGCTG
CG105716-05
DNA Sequence	CCCTCGGCGCGTCCGGACAGGGCCAGAGCCCGTTGGGCTCAGACCTGGGCCCGCAGATGCTTCCGGAA
	CTGCAGGAAACCAACGCGGCGCTGCAGGACGTGCCGGACTGGCTGCGCCAGCACGTCAGGGAGATCAC
	GTTCCTGAAAAACACGGTGATGGAGTGTGACGCCTGCGCGATGCAGCAGTCAGTACGCACCGGCCTAC
	CCAGCGTGCGGCCCCTGCTCCACTGCGCGCCCGGCTTCTGCTTCCCCGGCGTGGCCTGCATCCAGACG
	GAGAGCGGCGGCCGCTGCGGCCCCTGCCCCGCGGGCTTCACGGGCAACGGCTCGCACTGCACCGACGT
	CAACGAGTGCAACGCCCACCCCTGCTTCCCCCGAGTCCCCTGTATCAACACCAGCCCGGGGTTCCGCT
	GCGAGGCTTGCCCGCCGGGGTACAGCGGCCCCACCCACCAGGGCGTGCGGCTGGCTTTCGCCAAGGCC
	AACAAGCAGGTTTGCACGGACATCAACGAGTGTGAGACCGCGCAACATAACTGCGTCCCCAACTCCGT
	GTGCATCAACACCCGGGGCTCCTTCCAGTGCCGCCCGTGCCAGCCCCGCTTCGTGGGCGACCACGCGT
	CCGGCTQCCAGCGCGGCGCACAGCGCTTCTGCCCCGACGGCTCGCCCAGCGAGTGCCACGAGCATGCA
	GACTGCGTCCTAGAGCGCGATGGCTCGCGGTCGTGCGTGTGTCGCGTTGGCTCGGCCGGCAACGGGAT
	CCTCTGTGGTCGCGACACTGACCTAGACGGCTTCCCGGACGAGAAGCTGCGCTGCCCGGAGCCGCAGT
	GCCGTAAGGACAACTCCGTGACTGTGCCCAACTCAGGGCAGGAGGATGTGGACCGCGATGGCATCGGA
	GACGCCTGCGATCCGGATGCCGACGGGGACCGGGTCCCCAATGAAAACGACAACTGCCCGCTGGTGCG
	GAACCCAGACCAGCCCAACACGGACGAGGACAAGTGGGGCGATGCGTGCGACAACTGCCGGTCCCAGA
	AGAACGACGACCAAAAGGACACAGACCAGGACGGCCCGGGCGATGCGTGCGACGACGACATCGACGGC
	GACCGGATCCGCAACCAGGCCGACAACTGCCCTAGGGTACCCAACTCAGACCAGAAGGACAGTGATCG
	CGATGGTATAGGGGATGCCTGTGACAACTGTCCCCAGAAGAGCAACCCGGATCAGCCGGATGTGGACC
	ACGACTTTGTGGGAGATGCTTGTGACAGCGATCAAGACCAGGATGGAGACGGACATCAGGACTCTCGG
	GACAACTGTCCCACGQTGCCTAACAGTGCCCAGGAGGACTCAGACCACGATGGCCAGCGTGATGCCTG
	CGACGACGACCACGACAATGACGGAGTCCCTQACAGTCGGGACGGCGTGGGCGACGTGTGCCAGGACG
	ACTTTGATGCAGACAAGGTGGTAGACAAGATCGACGTGTGTCCGGAGAACGCTGAAGTCACGCTCACC
	GACTTCAGGGCCTTCCAGACAGTCQTGCTGGACCCGGAGGGTGACGCGCAGATTGACCCCAACTGCGT
	GGTGCTCAACCAGGGAAGGGAGATCGTGCAGACAATGAACAGCGACCCAGGCCTGGCTGTGGGTTACA
	CTGCCTTCAATGGCGTGGACTTCGAGGGCACGTTCCATGTGAACACGGTCACGGATGACGACTATGCG
	GGCTTCATCTTTGGCTACCAGGACAGCTCCAGCTTCTACGTGGTCATGTCGAAGCAGATGGAGCAAAC
	GTATTGGCAGGCGAACCCCTTCCGTGCTGTGGCCGAGCCTGGCATCCAACTCAAGGCTGTGAAGTCTT
	CCACAGGCCCCGCGGAACAGCTGCGGAACGCTCTGTGGCATACAGGAGACACAGAGTCCCAGGTGCGG
	CTGCTGTGGAAGGACCCGCGAAACGTGGGTTGGAAGGACAAGAAGTCCTATCGTTGGTTCCTGCAGCA
	CCGGCCCCAAGTGGGCTACATCAGGGTGCGATTCTATGAGGGCCCTGAGCTGGTGGCCGACAGCAACG
	TGGTCTTGGACACAACCATGCGGGGTCGCCGCCTGGGGGTCTTCTGCTTCTCCCAGGAGAACATCATC
	TGGGCCAACCTGCGTTACCGCTGCAATGACACCATCCCAGAGGACTATGAGACCCATCAGCTGCGGCA
	AGCCTAGGGACCAGGGTGAGGACCCGCCGGATGACAGCCACCCTCACCGCGGCTGGATGGGGGCTCTG
	CACCCAGCCCAAGGGGTCGCCGTCCTGAGGCGGAAGTGAG
	ORF Start: ATG at 26		ORF Stop: TAG at 2249
	SEQ ID NO:16	741 aa	MW at 81050.7 kD
NOV3b,	MVPDTACVLLLTLAALGASGQGQSPLGSDLGPQMLRELQETNAALQDVRDWLRQQVREITFLKNTVME
CG105716-05
Protein	CDACGMQQSVRTGLPSVRPLLHCAPGFCFPGVACIQTESGGRCGPCPAGFTGNGSHCTDVNECNAHPC
Sequence
	FPRVRCINTSPGFRCEACPPGYSGPTHQGVGLAFAKANKQVCTDINECETGQHNCVPNSVCINTRGSF
	QCGPCQPGFVGDQASGCQRGAQRFCPDGSPSECHEHADCVLERDGSRSCVCRVGWAGNGILCGRDTDL
	DGFPDEKLRCPEPQCRKDNCVTVPNSCQEDVDRDGIGDACDPDADGDGVPNEKDNCPLVRNPDQRNTD
	EDKWGDACDNCRSQKNDDQKDTDQDGRGDACDDDIDCDRIRNQADNCPRVPNSDQKDSDGDGIGDACD
	NCPQKSNPDQADVDHDFVGDACDSDQDQDGDQHQDSRDNCPTVPNSAQEDSDHDGQCDACDDDDDNDG
	VPDSRDGVGDVCQDDFDADKVVDKIDVCPENAEVTLTDFRAFQTVVLDPEGDAQIDPNWVVLNQGREI
	VQTMNSDPCLAVGYTAFNGVDFEGTFHVNTVTDDDYAGFIFGYQDSSSFYVVMWKQMEQTYWQANPFR
	AVAEPGIQLKAVKSSTGPGEQLRNALWHTGDTESQVRLLWKDPRNVGWKDKKSYRWFLQHRPQVGYIR
	VRFYEGPELVADSNVVLDTTMRGGRLGVFCFSQENIIWANLRYRCNDTIPEDYETHQLRQA
	SEQ ID NO:17	2307 bp
NOV3c,	CAGCACCCAGCTCCCCGCCACCCCCATGGTCCCCGACACCGCCTGCGTTCTTCTGCTCACCCTGGCTG
CG105176-06
DNA Sequence	CCCTCGGCGCGTCCGCACACGCCCAGAGCCCGTTGCGCTCAGACCTCGGCCCGCAGATGCTTCGCGAA
	CTGCAGGAAACCAACGCCGCGCTGCAGGACGTGCGGGACTGGCTGCGGCAGCAGGTCAGGGAGATCAC
	GTTCCTGAAAAACACGGTGATCGAGTGTGACGCGTGCGGGATGCAGCACTCAGTACGCACCGGCCTAC
	CCAGCGTGCGGCCCCTGCTCCACTGCGCGCCCGGCTTCTGCTTCCCCGCCGTGGCCTGCATCCAGACG
	GAGAGCGGCGGCCGCTGCGGCCCCTGCCCCGCCGGCTTCACGGCCAACGGCTCGCACTGCACCCACGT
	CAACGAGTCCAACGCCCACCCCTGCTTCCCCCGAGTCCCCTGTATCAACACCAGCCCGGGGTTCCQCT
	GCGAGGCTTGCCCGCCGGGGTACAGCGGCCCCACCCACCAGGGCGTGGGGCTGGCTTTCGCCAAGGCC
	AACAAQCAGGTTTGCACGGACATCAACGAGTGTGAGACCGGGCAACATAACTGCGTCCCCAACTCCGT
	GTGCATCAACACCCGGCGCTCCTTCCAGTGCGGCCCGTGCCAGCCCGGCTTCGTGGGCGACCACGCGT
	CCGGCTGCCAGCGCGGCGCACAGCGCTTCTGCCCCGACCGCTCGCCCAGCGAGTGCCACGAGCATGCA
	GACTGCGTCCTAGACCGCGATGGCTCGCGGTCGTGCGTGTGTCGCGTTGGCTCCGCCGGCAACGGGAT
	CCTCTGTGGTCGCGACACTGACCTAGACGGCTTCCCGGACGAGAAGCTGCGCTGCCCGGAGCCGCAGT
	GCCGTAAGGACAACTGCGTGACTGTGCCCAACTCACGGCAGGAGGATGTGGACCGCGATGGCATCGGA
	GACGCCTGCGATCCCGATGCCGACGGGGACGGGGTCCCCAATGAAAAQGACAACTGCCCGCTQGTGCG
	GAACCCAGACCAGCGCAACACGCACGAGGACAAGTGGGGCGATCCGTGCGACAACTGCCGGTCCCAGA
	AGAACGACGACCAAAAGGACACAGACCAGGACGGCCGGGGCGATGCGTGCGACGACGACATCGACGGC
	GACCGGATCCGCAACCAGGCCGACAACTGCCCTACGGTACCCAACTCAGACCAGAAGGACAGTGATGG
	CGATGGTATAGGGGATGCCTGTGACAACTGTCCCCAGAAGAGCAACCCGGATCACGCCGATGTGGACC
	ACGACTTTGTGGGAGATGCTTGTGACAGCGATCAAGACCAGGATCGAGACGGACATCAGGACTCTCGG
	GACAACTGTCCCACGGTGCCTAACAGTGCCCAGGAGGACTCAGACCACGATGGCCACGGTGATGCCTG
	CGACGACGACGTGTGCCAGGACGACTTTGATGCAGACAAGGTGGTAGACAAGATCGACGTGTGTCCGG
	AGAACGCTGAAGTCACGCTCACCGACTTCACGOCCTTCCAGACAGTCGTGCTGGACCCGGAGGGTGAC
	GCGCAGATTGACCCCAACTGGGTGGTGCTCAACCAGGGAAGQGAGATCGTGCAGACAATGAACAGCGA
	CCCACGCCTGGCTGTGGGTTACACTGCCTTCAATGGCGTGGACTTCGAGGGCACGTTCCATGTGAACA
	CGGTCACGOATGACGACTATGCGGGCTTCATCTTTGGCTACCAGGACAGCTCCAGCTTCTACGTGGTC
	ATGTGGAAGCAGATGGAGCAAACGTATTGGCAGGCGAACCCCTTCCGTGCTGTGGCCGAGCCTGCCAT
	CCAACTCAAGGCTGTGAAGTCTTCCACAGGCCCCGGGGAACAGCTGCGGAACGCTCTGTGGCATACAG
	GAGACACAGAGTCCCAGGTGCQGCTGCTGTGGAAGGACCCGCGAAACGTGGGTTGGAAGGACAAGAAG
	TCCTATCGTTCGTTCCTGCAGCACCCGCCCCAAGTGGGCTACATCAGGGTGCCATTCTATGAGGGCCC
	TGAGCTGGTGGCCGACAGCAACGTGGTCTTGGACACAACCATCCGGGGTCGCCGCCTGCGGGTCTTCT
	GCTTCTCCCAGGAGAACATCATCTGGGCCAACCTGCGTTACCGCTGCAATGACACCATCCCAGAGGAC
	TATGAGACCCATCAGCTCCGGCAAGCCTAGGGACCAGGGTGAGGACCCGCCGGATGACAGCCACCCTC
	ACCGCGGCTGGATGGGGGCTCTGCACCCAGCCCAAGGGGTGGCCQTCCTGAGGGCGAAGTGAG
	ORF Start: ATG at 26		ORF Stop: TAG at 2204
	SEQ ID NO:18	726 aa	MW at 79536.3 kD
NOV3c,	MVPDTACVLLLTLAALGASGQGQSPLGSDLGPQMLRELQETNAALQDVPDWLRQQVREITFLKNTVME
CG105716-06
Protein	CDACGMQQSVRTGLPSVRPLLHCAPGFCFPGVACIQTESGGRCGPCPAGFTGNGSHCTDVNECNAHPC
Sequence
	FPRVRCINTSPGFRCEACPPGYSGPTHQGVGLAFAKANKQVCTDINECETGQHNCVPNSVCINTRGSF
	QCGPCQPGFVGDQASGCQRGAQRFCPDGSPSECHEHADCVLERDQSRSCVCRVGWAGNGILCCRDTDL
	DGPPDEKLRCPEPQCRKDNCVTVPNSGQEDVDRDGIGDACDPDADGDGVPNEKDNCPLVRNPDQRNTD
	EDKWGDACDNCRSQKMDDQKDTDQDGRQDACDDDIDQDRIRNQADNCPRVPNSDQKDSDGDGIGDACD
	NCPQKSNPDQADVDHDFVGDACDSDQDQDGDGHQDSRDNCPTVPNSAQEDSDHDGQGDACDDDVCQDD
	FDADKVVDKIDVCPENAEVTLTDFRAFQTVVLDPEGDAQIDPNWVVLNQGREIVQTMNSDPGLAVGYT
	AFNGVDFEGThHVNTVTDDDYAGFIFGYQDSSSFYVVMWKQMEQTYWQANPFRAVAEPGIQLKAVKSS
	TGPGEQLRNALWHTGDTESQVRLLWKDPRNVGWKDKKSYRWFLQHRPQVGYIRVRFYEGPELVADSNV
	VLDTTMRGCRLGVFCFSQENIIWANLRYRCNDTIPEDYETHQLRQA
	SEQ ID NO:19	2374 bp
NOV3d,	CAGCACCCAGCTCCCCGCCACCGCCATGGTCCCCGACACCGCCTGCGTTCTTCTGCTCACCCTGGCTG
CG105716-04
DNA Sequence	CCCTCGGCGCGTCCGGACAGCGCCAGAGCCCGTTCGGCTCAGACCTGCGCCCGCAGATGCTTCGGGAA
	CTGCAGGAAACCAACGCGGCGCTGCAGGACGTGCGGGACTGGCTGCGGCAGCAGGTCACGGAGATCAC
	GTTCCTGAAAAACACCGTGATGGAGTGTGACGCGTGCGGGATGCAGCAGTCAGTACGCACCGGCCTAC
	CCAGCGTGCGGCCCCTGCTCCACTGCGCCCCCGGCTTCTGCTTCCCCGGCGTGGCCTGCATCCAGAC~
	GAGAGCGGCGGCCGCTGCGGCCCCTGCCCCGCGGGCTTCACGGGCAACCGCTCGCACTGCACCGACGT
	CAACGAGTGCAACGCCCACCCCTGCTTCCCCCGAGTCCGCTGTATCAACACCAGCCCCGGGTTCCGCT
	GCGAGGCTTGCCCGCCGGCGTACAGCCGCCCCACCCACCAGGGCGTGGGGCTGGCTTTCGCCAA~GCC
	AACAAGCAGGTTTGCACGGACATCAACGAGTGTGAGACCCGGCAACATAACTGCGTCCCCAACTCCGT
	GTGCATCAACACCCGGGGCTCCTTCCAGTGCGGCCCGTGCCAGCCCGGCTTCGTGGGCGACCACGCGT
	CCGGCTCCCAGCGCGGCGCACAGCGCTTCTGCCCCGACGGCTCGCCCAGCGAGTGCCACGAGCATGCA
	GACTGCGTCCTAGAGCGCGATGGCTCGCGGTCGTGCGTGTGTCGCGTTGGCTGGGCCGGCAACGGGAT
	CCTCTGTGGTCGCGACACTGACCTAGACGGCTTCCCGGACGAGAAGCTGCGCTCCCCGGAGCCCCAGT
	GCCGTAACGACAACTGCGTGACTGTGCCCAACTCAGGGCAGGAGGATGTGGACCGCGATGGCATCGGA
	GACGCCTGCGATCCGGATGCCGACGGGGACCGGGTCCCCAATGAAAAGGACAACTGCCCGCTGGTGCG
	GAACCCAGACCAGCGCAACACGGACGAGGACAAGTGGGGCCATGCGTGCGACAACTGCCGGTCCCAGA
	AGAACGACGACCAAAAGGACACAGACCAGGACGGCCGGGGCGATGCGTGCGACGACGACATCGACGGC
	GACCGGATCCGCAACCAGGCCCACAACTGCCCTAGGGTACCCAACTCAGACCAGAAGQACAGTGATGG
	CGATCGTATAGGGGATGCCTGTGACAACTGTCCCCAGAAGAACAACCCGGATCAGCCGGATGTCGACC
	ACGACTTTGTCGGAGATGCTTGTGACAGCGATCAAGACCAGGATGGAGACGGACATCAGGACTCTCGG
	GACTCTCCGGACTCAGACCACGATGGCCAGGGTGATGCCTGCGACGACGACGACGACAATGACGGAGT
	CCCTGACAGTCGCGACAACTGCCGCCTGGTGCCTAACCCCGGCCAGGAGGACGCGGACAGGGACGGCG
	TGGGCGACGTGTGCCACGACGACTTTGATGCAGACAAGGTGGTAGACAAGATCGACGTGTGTCCGGAG
	AACGCTGAAGTCACCCTCACCGACTTCACGGCCTTCCAGACAGTCGTGCTGGACCCGGAGCGTGACGC
	GCAGATTGACCCCAACTGGGTGGTGCTCAACCAGGGAAGGGAGATCGTGCAGACAATGAACAGCGACC
	CAGGCCTCGCTGTGGGTTACACTGCCTTCAATGGCGTGGACTTCGAGGGCACGTTCCATGTGAACACG
	GTCACGGATGACGACTATGCGGGCTTCATCTTTGGCTACCAGGACAGCTCCAGCTTCTACGTGGTCAT
	GTGGAAGCAGATCGAGCAAACGTATTGGCAGGCGAACCCCTTCCGTGCTGTGGCCGAGCCTGGCATCC
	AACTCAAGGCTGTGAAGTCTTCCACAGGCCCCGGGGAACAGCTGCGGAACGCTCTGTGGCATACACGA
	GACACAGAGTCCCAGGTGCGGCTGCTGTGGAAGGACCCGCGAAACGTGGGTTGCAAGGACAAGAAGTC
	CTATCGTTGGTTCCTGCAGCACCCGCCCCAAGTGGGCTACATCAGGGTGCGATTCTATCAGGGCCCTG
	AGCTGGTGGCCGACAGCAACGTGGTCTTGGACACAACCATGCGGGCTCGCCGCCTGGCGGTCTTCTGC
	TTCTCCCAGGAGAACATCATCTGGGCCAACCTGCGTTACCGCTGCAATGACACCATCCCAGAGGACTA
	TGAGACCCATCAGCTGCGGCAAGCCTAGGGACCAGGGTGAGGACCCGCCGGATGACAGCCACCCTCAC
	CGCGGCTGGATGGGGCCTCTGCACCCAGCCCCAAGGGOTGGCCGTCCTGAGGGGGAAGTGAG
	ORF Start: ATG at 26		ORF Stop: TAG at 2270
	SEQ ID NO: 20	748 aa	MW at 81933.6 kD
NOV3d,	MVPDTACVLLLTLAALGASGQGQSPLGSDLGPQMLRELQETNAALQDVRDWLRQQVREITFLKNTVME
CG105716-04
Protein	CDACGMQQSVRTGLPSVRPLLHCAPGFCFPGVACIQTESGGRCGPCPAGFTGNGSHCTDVNECNAHPC
Sequence
	FPRVRCINTSPGFRCEACPPGYSGPTHQGVGLAFAKANKQVCTDINECETGQHNCVPNSVCINTRGSF
	QCGPCQPGFVGDQASGCQRGAQRFCPDGSPSECHEHADCVLERDGSRSCVCRVGWAGNGILCGRDTDL
	DGFPDEKLRCPEPQCRKDNCVTVPNSGQEDVDRDGIGDACDPDADGDGVPNEKDNCPLVRNPDQRNTD
	EDKWGDACDNCRSQKNDDQKDTDQDGRGDACDDDIDQDRIRNQADNCPRVPNSDQKDSDGDGIGDACD
	NCPQKSNPDQADVDHDFVGDACDSDQDQDGDGHQDSRDSRDSDHDGQQDACDDDDDNDGVPDSRDNCR
	LVPNPGQEDADRDGVGDVCQDDFDADKVVDKIDVCPENAEVTLTDFRAFQTVVLDPEGDAQIDPNWVV
	LNQGREIVQTMNSDPGLAVGYTAFNGVDFEGTFHVNTVTDDDYAGFIFCYQDSSSFYVVMWKQMEQTY
	WQANPFRAVAEPGIQLKAVKSSTGPGEQLRNALWHTGDTESQVRLLWKDPRNVGWKDKKSYRWFLQHR
	PQVGYIRVRFYEGPELVADSNVVLDTTMRGGRLGVFCFSQENIIWANLRYRCNDTIPEDYETHQLRQA
	SEQ ID NO:21	2293 bp
NOV3e,	CAGCACCCAGCTCCCCGCCACCGCCATGGTCCCCGACACCGCCTGCGTTCTTCTGCTCACCCTGCCTG
CG105176-03
DNA Sequence	CCCTCGQCGCGTCCGGACACGGCCAGAGCCCGTTGGGCTCAGACCTGGGCCCGCAGATGCTTCGGGAA
	CTGCAGGAAACCAACGCGGCGCTGCAGGACGTGCGCGACTGGCTGCGGCAGCAGGTCAGGGAGATCAC
	GTTCCTGAAAAACACGGTGATGGAGTGTGACGCGTGCGGGATGCAGCAGTCAGTACGCACCQGCCTAC
	CCAGCGTGCGGCCCCTGCTCCACTCCGCGCCCGGCTTCTGCTTCCCCGGCGTGGCCTGCATCCAGACG
	GAGAGCCGCGGCCGCTGCGGCCCCTGCCCCGCGGGCTTCACGGGCAACGGCTCGCACTGCACCGACGT
	CAACGAGTCCAACGCCCACCCCTGCTTCCCCCGAGTCCGCTGTATCAACACCAGCCCGGGGTTCCGCT
	GCGAGGCTTGCCCGCCGCGGTACAGCGGCCCCACCCACCAGGGCGTGGGGCTGGCTTTCGCCAAGGCC
	AACAAGCAGGTTTGCACGGACATCAACGAGTGTGAGACCCGGCAACATAACTGCGTCCCCAACTCCGT
	GTGCATCAACACCCGGGGCTCCTTCCAGTGCGGCCCGTGCCAGCCCGGCTTCGTOGGCGACCACGCGT
	CCGGCTGCCAGCGCCGCGCACAGCGCTTCTGCCCCGACGGCTCGCCCAGCGAGTGCCACGAGCATGCA
	GACTGCGTCCTAGAGCGCGATGGCTCGCGGTCGTGCGTGTGTCGCGTTGGCTGGGCCGGCAACGGCAT
	CCTCTGTGGTCGCGACACTGACCTAGACQGCTTCCCGGACGACAAGCTGCCCTGCCCGGAGCCQCAGT
	GCCGTAAGGACAACTGCGTGACTGTGCCCAACTCAGGGCAGGAGGATGTGGACCGCGATCGCATCCGA
	GACGCCTGCGATCCGGATGCCGACGGGGACGGGGTCCCCAATGAAAAGGACAACTGCCCGCTGGTGCG
	GAACCCAGACCAGCGCAACACGGACGAGGACAAGTGGGGCGATGCGTGCGACAACTGCCGGTCCCAGA
	AGAACCACGACCAAAAGGACACAGACCAGGACGGCCGGGGCGATGCGTCCGACGACGACATCGACGGC
	CACCGGATCCGCAACCAGGCCGACAACTGCCCTAGGGTACCCAACTCAGACCAGPAGGACAGTCATGG
	CGATGGTATAGGGGATGCCTGTGACAACTGTCCCCAGAAGAGCAACCCGGATCAGGCGGATGTGGACC
	ACGACTTTGTGGGAGATGCTTGTGACACCGATCAAQACCAGGATGGAGACGGACATCAGGACTCTCGG
	GACAACTGCCGCCTGGTGCCTAACCCCGGCCAGGAGGACGCGGACAQGGACGGCGTCGGCGACGTGTG
	CCAGCACGACTTTGATGCAGACAAGGTGGTAGACAAGATCGACGTGTGTCCGGAGAACGCTGAAGTCA
	CGCTCACCGACTTCAGGGCCTTCCAGACAGTCGTGCTGGACCCCGAGGGTGACGCGCAGATTQACCCC
	AACTGGGTGGTGCTCAACCACGGAAGGGAGATCGTGCAGACAATGAACAGCGACCCACGCCTGGCTGT
	GGGTTACACTGCCTTCAATGGCGTGGACTTCGACGGCACGTTCCATGTGAACACGGTCACGGATCACG
	ACTATGCGGGCTTCATCTTTGGCTACCAGGACAGCTCCAGCTTCTACGTGGTCATGTGGAAGCAGATG
	GAGCAAACGTATTGGCAGGCGAACCCCTTCCGTGCTGTGGCCGAGCCTGGCATCCAACTCAAGGCTGT
	GAAGTCTTCCACAGGCCCCGGGGAACAGCTGCGGAACGCTCTGTGGCATACAGGAGACACAGAGTCCC
	AGGTGCGGCTGCTGTGGAAGGACCCGCGAAACGTGCGTTGGAAGGACAAGAAGTCCTATCGTTCGTTC
	CTGCAGCACCGGCCCCAAGTCGGCTACATCAGGGTGCGATTCTATGAGGGCCCTGAGCTGGTGGCCGA
	CAGCAACGTGGTCTTGGACACAACCATGCGCGGTGGCCGCCTGGGGGTCTTCTGCTTCTCCCAGGAGA
	ACATCATCTGGGCCAACCTGCGTTACCGCTGCAATGACACCATCCCAGACGACTATGAGACCCATCAG
	CTGCGGCAAGCCTAGGGACCAGGGTGAGGACCCGCCGGATGACAGCCACCCTCACCGCGGCTCGATGG
	GGGCTCTGCACCCAGCCCcAAGGGGTGGCCGTCCTGAGGGGGAAGTGAG
	ORF Start: ATG at 26		ORF Stop: TAG at 2189
	SEQ ID NO:22	721 aa	MW at 79058.0 kD
NOV3e,	MVPDTACVLLLTLAALGASGQGQSPLGSDLGPQMLRELQETNAALQDVRDWLRQQVREITFLKMTVME
CG105716-03
Protein	CDACGMQQSVRTGLPSVRPLLHCAPGFCFPGVACIQTESGGRCGPCPAGFTGNGSHCTDVNECNAHPC
Sequence
	FPRVRCINTSPGFRCEACPPGYSGPTHQGVGLAPAKANKQVCTDINECETGQHNCVPNSVCINTRGSF
	QCGPCQPGFVGDQASGCQRGAQRFCPDGSPSECHEHADCVLERDGSRSCVCRVCWACNGILCGRDTDL
	DGFPDEKLRCPEPQCRKDNCVTVPNSGQEDVDRDGIGDACDPDADGDGVPNEKDNCPLVRNPDQRNTD
	EDKWGDACDNCRSQKNDDQKDTDQDGRGDACDDDIDGDRIRNQADNCPRVPNSDQKDSDGDGIGDACD
	NCPQKSNPDQADVDHDFVGDACDSDQDQDGDGHQDSRDNCRLVPNPCQEDADRDGVGDVCQDDFDADK
	VVDKIDVCPENAEVTLTDFRAFQTVVLDPEGDAQIDPNWVVLNQGREIVQTMNSDPGLAVGYTAFNGV
	DFEGTFHVNTVTDDDYAGFIFGYQDSSSFYVVMWKQMEQTYWQANPFPAVAEPGIQLKAVKSSTGPGE
	QLRNALWHTGDTESQVRLLWKDPRNVGWKDKKSYRWFLQHRPQVGYIRVRFYEGPELVADSNVVLDTT
	MRGGRLGVFCFSQENIIWANLRYRCNDTIPEDYETHQLRQA
	SEQ ID NO:23	1386 bp
NOV3f,	AGATCTCAGGAGGATGTGGACCGCGATGGCATCGGAGACGCCTGCGATCCGGATGCCGACGGGGACGG
CG105716-02
DNA Sequence	CGTCCCCAATGAAAACGACAACTGCCCQCTGGTGCGGAACCCAGACCAGCGCAACACGGACOAGGACA
	AGTGGGGCGATGCGTGCGACAACTGCCGGTCCCAGAAGAACGACGACCAAAAGGACACAGACCACGAC
	GGCCGGGGCGATGCGTGCGACGACGACATCGACGQCGACCGGATCCGCAACCAGGCCGACAACTGCCC
	TAGGGTACCCAACTCAGACCAGAAGGACAGTCATGGCGATGGTATACGGGATOCCTGTGACAACTGTC
	CCCAGAAGAGCAACCCGGATCAGGCGGATGTGGACCACGACTTTGTCGGAGATGCTTGTGACAGCGAT
	CAAGACCAGGATGGAGACGGACATCAGGACTCTCGGGACAACTGTCCCACGGTGCCTAACAGTGCCCA
	CGAGGACTCAGACCACGATGGCCAGGGTGATGCCTGCGACGACGACGACGACAATGACCGAGTCCCTG
	ACAGTCGGGACAACTGCCGCCTGGTGCCTAACCCCGGCCAGGAGGACGCGGACAGCGACGGCGTGGCC
	GACGTGTGCCAGGACGACTTTGATGCAGACAAGGTGGTAGACAAGATCGACGTGTGTCCGGAGAACGC
	TGAAGTCACGCTCACCGACTTCAGGGCCTTCCAGACAGTCGTGCTGGACCCGGAQGGTGACGCGCAGA
	TTGACCCCAACTGGGTGGTGCTCAACCAGGGAAGGGAGATCGTGCAGACAATGAACAGCGACCCAGGC
	CTGGCTGTGGGTTACACTGCCTTCAATGGCGTGGACTTCGAGGGCACGTTCCATGTGAACACGGTCAC
	GGATGACGACTATGCGGGCTTCATCTTTGGCTACCAGGACAGCTCCAQCTTCTACGTGGTCATGTGGA
	AGCAGATQGAGCAAACGTATTGGCAGGCGAACCCCTTCCGTGCTGTGGCCGAGCCTGGCATCCAACTC
	AAGGCTGTGAAGTCTTCCACAGGCCCCGGGGAACAGCTGCGGAACGCTCTGTGGCATACACGACACAC
	AGAGTCCCAGCTGCGGCTGCTGTCGAAGGACCCGCGAAACGTGGGTTGCAAGGACAAGAAGTCCTATC
	GTTGGTTCCTGCAGCACCGGCCCCAAGTGGGCTACATCAGGGTGCGATTCTATGAGGGCCCTGAGCTG
	GTGGCCGACAGCAACGTGGTCTTGGACACAACCATGCQGGGTGGCCGCCTGGGGGTCTTCTGCTTCTC
	CCAGGAGAACATCATCTGGGCCAACCTGCGTTACCGCTGCAATGACACCATCCCAGAGGACTATGAGA
	CCCATCAGCTGCGGCAAGCCCTCGAG
	ORF Start: at 7		ORF Stop: at 1381
	SEQ ID NO:24	458 aa	MW at 51108.1 kD
NOV3f,	QEDVDRDGIGDACDPDADGDGVPNEKDNCPLVRNPDQRNTDEDKWGDACDNCRSQKNDDQKDTDQDGR
CG105716-02
Protein	GDACDDDIDGDRIRNQADNCPRVPNSDQKDSDGDGIGDACDNCPQKSNPDQADVDHDFVGDACDSDQD
Sequence
	QDQDGHQDSRDNCPTVPNSAQEDSDHDCQGDACDDDDDNDGVPDSRDNCRLVPNPGQEDADRDGVGDV
	CQDDFDADKVVDKIDVCPENAEVTLTDFRAFQTVVLDPEGDAQIDPNNVVLNQGREIVQTMNSDPGLA
	VGYTAFNGVDFEGTFHVNTVTDDDYAGFIFGYQDSSSFYVVMWKQMEQTYWQANPFRAVAEPQIQLKA
	VKSSTGPGEQLRNALWHTGDTESQVRLLWKDPRNVGWKDKKSYRWFLQHRPQVGYIRVRFYEGPELVA
	DSNVVLDTTMROGRLGVFCFSQENIIWANLRYRCNDTIPEDYETHQLRQA
	SEQ ID NO:25	2274 bp
NOV3g,	ATGGTCCCCGACACCGCCTGCGTTCTTCTGCTCACCCTGGCTGCCCTCGGCGCGTCCGGACAGGGCCA
CG105716-01
DNA Sequence	GAGCCCGTTGGGCTCAGACCTGGGCCCGCAGATGCTTCGGGAACTGCAGGAAACCAACGCGGCGCTGC
	AGGACGTGCGGGACTCGCTGCGGCACCAGGTCAGGGAGATCACGTTCCTGAAAAACACGGTGATGGAG
	TGTGACGCGTGCGGGATGCAGCAGTCAGTACGCACCCGCCTACCCAGCGTGCGGCCCCTGCTCCACTG
	CGCGCCCGGCTTCTGCTTCCCCGGCGTGGCCTGCATCCAGACGGAGAGCGGCGGCCGCTGCCGCCCCT
	GCCCCGCGGGCTTCACGGGCAACGGCTCGCACTGCACCGACGTCAACGAGTGCAACGCCCACCCCTGC
	TTCCCCCGAGTCCGCTGTATCAACACCAGCCCGCGGTTCCGCTGCCAGGCTTGCCCGCCGGGGTACAG
	CGGCCCCACCCACCAQGGCGTGGGGCTGGCTTTCGCCAAGGCCAACAAGCAGGTTTGCACGGACATCA
	ACGAGTGTGAGACCGGOCAACATAACTGCGTCCCCAACTCCGTGTGCATCAACACCCGGGGCTCCTTC
	CAGTGCGGCCCGTGCCAGCCCGGCTTCGTGGGCGACCAGGCGTCCCGCTGCCAGCGGCGCGCACAGCG
	CTTCTGCCCCGACGGCTCGCCCAGCGAGTGCCACCAGCATGCAGACTGCGTCCTAGAGCGCGATGGCT
	CGCGGTCGTGCGTGTGTGCCGTTGGCTGGGCCGGCAACGGGATCCTCTGTGGTCCCGACACTGACCTA
	GACGGCTTCCCGGACGAGAAGCTGCGCTGCCCGGAGCGCCAGTGCCGTAAGGACAACTGCGTGACTGT
	GCCCAACTCAGGGCAGCAGGATCTGGACCGCGATCGCATCGGAGACGCCTGCGATCCGGATGCCGACG
	GGGACCGGGTCCCCAATGAAAAGGACAACTGCCCGCTGGTGCGGAACCCAGACCAGCGCAACACGGAC
	GAGGACAAGTGGGGCGATGCGTGCGACAACTGCCGGTCCCAGAAGAACGACGACCAAAAGGACACAGA
	CCAGGACGGCCGGGGCGATGCGTGCQACGACGACATCGACGGCGACCCGATCCGCAACCAOGCCGACA
	ACTCCCCTACGGTACCCAACTCAGACCAGAAGGACAGTGATGGCGATGGTATAGGGGATGCCTGTGAC
	AACTGTCCCCAGAAGAGCAACCCGGATCAGGCGCATGTGGACCACCACTTTGTCGGAGATGCTTGTGA
	CAGCGATCAAGACCAGGATGGAGACGGACATCAGGACTCTCGGGACAACTGTCCCACGGTQCCTAACA
	GTGCCCAGGAGGACTCACACCACGATGGCCAGGGTCATGCCTGCGACGACGACGACGACAATGACGGA
	GTCCCTGACAGTCOGGACAACTGCCGCCTGGTGCCTAACCCCGGCCAGGAGGACCCCGACAGGGACGG
	CGTGGGCGACGTGTGCCAGGACGACTTTGATGCAGACAAGGTGGTAGACAAGATCGACGTGTGTCCGG
	AGAACGCTGAAGTCACGCTCACCGACTTCAGGGCCTTCCAGACAGTCCTCCTGGATCCTGAAGCGGAT
	GCCCAGATCGATCCCAACTGGGTGGTCCTGAACCAGGGCATGGAGATTGTACAGACCATGAACAGTGA
	TCCTQQCCTGGCAGTGGGGTACACAGCTTTTAATGGAGTTGACTTCGAAGCGACCTTCCATGTGAATA
	CCCAGACAGATGATGACTATGCAGCCTTTATCTTTGGCTACCAAGATAGCTCCAGCTTCTACGTGQTC
	ATGTGGAAGCAGACGGAGCAGACATATTGCCAAGCCACCCCATTCCGAGCAGTTGCAGAACCTGOCAT
	TCAGCTCAACGGCTGTGAGTCTAAQACAGGTCCAQGGGAGCATCTCCCGAACGCTCTGTGGCATACAG
	GAGACACAGAGTCCCAQGTGCCGCTGCTGTGGAAGGACCCGCGAAACGTGGGTTGGAAGGACAAGAAG
	TCCTATCGTTGGTTCCTGCAGCACCGGCCCCAAGTGGGCTACATCAGCGTCCGATTCTATGAGGGCCC
	TGAGCTGGTGGCCQACAGCAACGTGGTCTTGGACACAACCATGCGCGCTGGCCGCCTGGGGGTCTTCT
	GCTTCTCCCAGGAGAACATCATCTGGGCCAACCTGCGTTACCGCTGCAATGACACCATCCCAGAGGAC
	TATGAGACCCATCAGCTGCQGCAAGCCTAG
	ORF Start: ATG at 1		ORF Stop: TAG at 2272
	SEQ ID NO: 26	757 aa	MW at 82915.7 kD
NOV3g,	MVPDTACVLLLTLAALGASGQGQSPLGSDLGPQMLRELQETNAALQDVRDWLRQQVREITFLKNTVME
CG105716-01
Protein	CDACGMQQSVRTQLPSVRPLLHCAPGFCFPGVACIQTESGGRCGPCPAGFTGNGSHCTDVNECNAHPC
Sequence
	FPRVRCINTSPGFRCEACPPCYSGPTHQGVGLAFAKANKQVCTDINECETCQHNCVPNSVCINTRGSF
	QCGPCQPGFVGDQASGCQRRAQRFCPDGSPSECHEHADCVLERDGSRSCVCAVGWAGNGILCGRDTDL
	DGFPDEKLRCPERQCRKDNCVTVPNSGQEDVDRDGIGDACDPDADGDGVPNEKDNCPLVRNPDQRNTD
	EDKWGDACDNCRSQKNDDQKDTDQDGRGDACDDDIDGDRIRNQADNCPRVPNSDQKDSDGDGIGDACD
	NCPQKSNPDQADVDHDFVGDACDSDQDQDGDGHQDSRDNCPTVPNSAQEDSDHDGQGDACDDDDDNDG
	VPDSRDNCRLVPNPGQEDADRDGVGDVCQDDFDADKVVDKIDVCPENAEVTLTDFRAFQTVVLDPECD
	AQIDPNWVVLNQQMEIVQTMNSDPGLAVGYTAFNGVDFEGTFHVNTQTDDDYAGFIFGYQDSSSFYVV
	MWKQTEQTYWQATPFRAVAEPGIQLKAVKSKTGPGEHLRNALWHTGDTESQVRLLWKDPRNVGWKDKK
	SYRWFLQHRPQVGYIRVRFYEGPELVADSNVVLDTTMRGGRLGVFCFSQENIIWAULRYRCNDTIPED
	YETHQLRQA
	SEQ ID NO:27	1386 bp
NOV3h,	AGATCTCAGGAGGATGTGGACCGCGATGGCATCGGAGACGCCTGCGATCCGGATGCCGACCGGGACGG
207569245
DNA Sequence	GGTCCCCAATGAAAAGGACAACTGCCCGCTGGTGCGGAACCCAGACCAQCGCAACACGGACGAGGACA
	AGTGGGGCGATGCGTGCGACAACTGCCGGTCCCAGAAGAACGACGACCAAAAGGACACAGACCAGGAC
	GGCCGGGGCGATGCGTGCGACGACGACATCGACCGCGACCGCATCCGCAACCAGGCCQACAACTGCCC
	TAGGGTACCCAACTCAGACCAGAAGGACAGTGATGGCGATGGTATAGGGGATGCCTGTGACAACTGTC
	CCCAGAAGAGCAACCCGCATCAGGCCGATGTGGACCACCACTTTGTGGGAGATGCTTGTGACAGCGAT
	CAAGACCAGGATGGAGACGGACATCAGGACTCTCGGGACAACTGTCCCACCGTGCCTAACAGTGCCCA
	GGAGGACTCAGACCACGATGGCCAGGGTGATGCCTGCGACGACGACGACGACAATGACGGAGTCCCTG
	ACAGTCGGGACAACTGCCGCCTGGTGCCTAACCCCGGCCAGGACGACGCCGACAGGGACGGCGTGGGC
	GACGTGTGCCAGGACGACTTTGATGCAGACAAGGTGGTACACAAGATCGACGTCTGTCCGGAGAACGC
	TGAAGTCACGCTCACCGACTTCAGGGCCTTCCAGACAGTCGTGCTCGACCCGGAGGGTGACGCGCAGA
	TTGACCCCAACTCGGTGGTGCTCAACCAGGGAAGGGAGATCGTGCAGACAATGAACAGCGACCCAGGC
	CTGGCTGTGGTTACACTGCCTTCAATGGCGTGGACTTCGAGGGGCACGTTCCATGTGAACACGGTCAC
	GGATGACGACTATGCGGGCTTCATCTTTCGCTACCAGGACAGCTCCAGCTTCTACGTGGTCATGTGGA
	AGCAGATCGAGCAAACGTATTCGCACGCGAACCCCTTCCGTGCTGTGGCCGAGCCTGGCATCCAACTC
	AAGGCTGTGAACTCTTCCACACGCCCCGGGGAACAGCTGCGGAACGCTCTGTGGCATACAGCAGACAC
	AGAGTCCCAGGTGCGGCTGCTGTGGAAGGACCCGCGAAACGTGGGTTGGAAGGACAAGAAGTCCTATC
	GTTGGTTCCTGCAGCACCGGCCCCAAGTGGGCTACATCAGGGTGCGATTCTATGAGGGCCCTGAGCTG
	GTGGCCGACAGCAACGTCGTCTTGGACACAACCATGCCGCGTCGCCGCCTCGCGGTCTTCTGCTTCTC
	CCAGGAGAACATCATCTGGGCCAACCTGCGTTACCGCTGCAATGACACCATCCCAQAGGACTATGAGA
	CCCATCAGCTGCGGCAAGCCCTCGAG
	ORF Start: at 1		ORF Stop: end of sequence
	SEQ ID NO:28	462 aa	MW at 51593.6 kD
NOV3h,	RSQEDVDRDGIGDACDPDADGDGVPNEKDNCPLVRNPDQRNTDEDKWGDACDNCRSQKNDDQKDTDQD
207569245
Protein	CRGDACDDDIDGDRIRNQADNCPRVPNSDQKDSDGDGIGDACDNCPQKSNPDQADVDHDFVGDACDSD
Sequence
	QDQDGDGHQDSRDNCPTVPNSAQEDSDHDGQCDACDDDDDNDGVPDSRDNCRLVPNPGQEDADRDGVG
	DVCQDDFDADKVVDKIDVCPENAEVTLTDFRAFQTVVLDPECDAQIDPNNVVLNQGREIVQTMNSDPG
	LAVGYTAFNGVDFEGTFHVNTVTDDDYAGFIFGYQDSSSFYVVMWKQMEQTYWQANPFRAVAEPGIQL
	KAVKSSTGPGEQLRNALWHTGDTESQVRLLWKDPRNVGWKDKKSYRWFLQIIRPQVGYI RVRFYEQPEL
	VADSNVVLDTTMRGGRLGVFCFSQENIIWANLRYRCNDTIPEDYETHQLRQALE
	SEQ ID NO:29	1386 bp
NOV3i,	AGATCTCACGAGGATGTGGACCGCGATCGCATCGGAGACGCCTGCGATCCGGATGCCGACGGGGACGG
207569277
DNA Sequence	GGTCCCCAATGAAAAGGACAACTGCCCGCTGGTGCGGAACCCAGACCAGCGCAACACGGACGAGGACA
	AGTGGGGCGATGCCTGCGACAACTGCCCGTCCCAGAAGAACGACGACCAAAAGGACACAGACCAGGAC
	CGCCGCGGCGATGCGTGCGACGACGACATCCACGGCCACCGGATCCGCAACCACGCCGACAACTGCCC
	TAGGGTACCCAACTCAGACCAGAAGGACAGTGATGGCGATGGTATAGGGGATGCCTGTGACAACTGTC
	CCCAGAAGAGCAACCCCGATCAGGCGGATGTGGACCACGACTTTGCGGGAGATGCTTGTGACAGCGAT
	CAAGACCAGGATGGAGACGGACATCAGGACTCTCGGGACAACTGTCCCACGGTGCCTAACAGTGCCCA
	GGAGGACTCAGACCACGATCGCCACGGTGATGCCTGCGACGACGACGACGACAATGACGGAGTCCCTG
	ACAGTCGGGACAACTGCCGCCTGGTGCCTAACCCCGGCCAGCAGGACCCGGACAGGGACGGCGTGGGC
	GACGTGTQCCAGGACGACTTTGATGCAGACAAGGTGGTAGACAACATCCACGTGTGTCCGGAGAACGC
	TGAAGTCACGCTCACCGACTTCAGGGCCTTCCAGACAGTCGTGCTGGACCCGGAGCGTGACGCCCAGA
	TTCACCCCAACTGGGTGGTGCTCAACCAGGQAACGGACATCGTGCAGACAATGAACAGCGACCCAGGC
	CTGGCTGTCGGTTACACTGCCTTCAATGGCGTGCACTTCGAGCGCACGTTCCATGTGAACACGGTCAC
	GCATGACGACTATGCGGGCTTCATCTTTGGCTACCAGGACAGCTCCAGCTTCTACGTCGTCATQTQGA
	AGCAGATGGAGCAAACGTATTCGCAGGCGAACCCCTTCCGTGCTGTGGCCGAGCCTGGCATCCAACTC
	AAGGCTGTGAAGTCTTCCACAGGCCCCCGGGAACAGCTGCGGAACGCTCTGTGGCATACAGGAGACAC
	AGAGTCCCAGGTGCGGCTGCTGTGGAAGGACCCGCGAAACGTGGCTTCGAAGGACAAGAAGTCCTATC
	GTTGGTTCCTGCAGCACCGGCCCCAAGTGGGCTACATCACGGTGCGATTCTATGAGGGCCCTGAGCTG
	GTGGCCGACAGCAACGTGGTCTTGGACACAACCATGCGGGGTGGCCGCCTGGGGGTCTTCTGCTTCTC
	CCAGGAGAACATCGTCTGCGCCAACCTGCGTTACCGCTGCAATGACACCATCCCAGAGGACTATCAGA
	CCCATCAGCTGCGGCAAGCCCTCGAG
	ORF Start: at 1		ORF Stop: end of sequence
	SEQ ID NO:30	462 aa	MW at 51551.6 kD
NOV3i,	RSQEDVDRDGIGDACDPDADGDGVPNEKDNCPLVRNPDQRNTDEDKWGDACDNCRSQKNDDQKDTDQD
207569277
Protein	GRGDACDDDIDGDRIRNQADNCPRVPNSDQKDSDGDGIGDACDNCPQKSNPDQADVDHDFAGDACDSD
Sequence
	QDQDGDGHQDSRDNCPTVPNSAQEDSDHDGQGDACDDDDDNDGVPDSRDNCRLVPNPGQEDADRDGVG
	DVCQDDFDADKVVDKIDVCPENAEVTLTDFRAFQTVVLDPEGDAQIDPNWVVLNQGREIVQTMNSDPG
	LAVGYTAFNGVDFEGTFHVNTVTDDDYAGFIFGYQDSSSFYVVMWKQMEQTYWQANPFRAVAEPGIQL
	KAVKSSTGPGEQLRNALWHTGDTESQVRLLWKDPRNVGWKDKKSYRWFLQHRPQVGYIRVRFYEGPEL
	VADSNVVLOTTMRGGRLGVFCFSQENIVWANLRYRCNDTIPEDYETHQLRQALE
	SEQ ID NO:31	11386 bp
NOV3j,	AGATCTCAGGAGGATGTGGACCGCGATGGCATCGGAGACGCCTGCGATCCGGATGCCGACGGGGACCG
207569281
DNA Sequence	GGTCCCCAATGAAAACGACAACTGCCCGCTGGTGCCGAACCCAGACCAGCQCAACACGGACGAQGACA
	AGTGGGGCGATGCGTGCGACAACTGCCGGTCCCAGAAGAACGACGACCAAAAGGACACAGACCACGAC
	GGCCGGGGCGATGCGTGCGACGACGACATCGACGGCGACCGGATCCGCAACCAGGCCGACAACTGCCC
	TAGGGTACCCAACTCAGACCAGAAGGACAGTGATCGCGATCGTATAGGGGATGCCTGTGACAACTGTC
	CCCAGAAGAGCAACCCCGATCAGGCGGATGTGGACCACGACTTTGTGGGAGATGCTTGTGACAGCGAT
	CAAGACCAGGATGGAGACCGACATCAGGACTCTCGGGACAACTGTCCCACGGTGCCTAACAGTGCCCA
	GGAGGACTCAGACCACCATGGCCAGGGTGATGCCTGCGACGACGACGACGACAATGACGGAGTCCCTC
	ACAGTCGGGACAACTGCCGCCTGGTGCCTAACCCCGGCCAGGAGGACGCGGACAGGGACGGCGTGGGC
	GACGTGTGCCAGGACGACTTTGATGCAGACAAGGTGGTAGACAAGATCGACGCGTGTCCCGAGAACGC
	TGAAGTCACGCTCACCGACTTCAGGGCCTTCCAGACAGTCGTGCTGGACCCGGAGGGTGACGCGCAGA
	TTGACCCCAACTGCGTGGTGCTCAACCAGCGAACGGAGATCGTGCAGACAATGAACAGCGACCCAGGC
	CTGGCTGTGGGTTACACTGCCTTCAATGGCGTGGACTTCGAGGGCACGTTCCATGTGAACACGGTCAC
	GGATGACGACTATGCGGGCTTCATCTTTGGCTACCAGGACAGCTCCACCTTCTACGTGGTCATGTGGA
	AGCAGATCGAGCAAACGTATTGGCAGGCGAACCCCTTCCGTGCTGTGGCCQAGCCTGGCATCCAACTC
	AAGGCTGTGAAGTCTTCCACAGGCCCCGGGGAACAGCTGCGGAACGCTCTGTGGCATACAGGAGACAC
	AGAGTCCCAGGTGCGGCTGCTGTGGAAGGACCCGCGAAACGTGGGTTGGAAGGACAAGAAGTCCTATC
	GTTGGTTCCTGCAGCACCCGCCCCAAGTGGGCTACATCAGGGTGCGATTCTATGAGGGCCCTGAGCTG
	GTGGCCGACAGCAACGTGGTCTTGGACACAACCATGCGGGGTGGCCGCCTOGGGGTCTTCTGCTTCTC
	CCAGGAGAACATCATCTGGGCCAACCTGCGTTACCGCTGCAATGACACCATCCCAGAGGACTATGAGA
	CCCATCAGCTGCGGCAAGCCCTCGAG
	ORF Start: at 1		ORF Stop: end of sequence
	SEQ ID NO: 32	462 aa	MW at 51565.6 kD
NOV3J,	RSQEDVDRDGIGDACDPDADGDGVPNEKDNCPLVRNPDQRNTDEDKWGDACDNCRSQKNDDQKDTDQD
207569281
Protein	GRGDACDDDIDGDRIRNQADNCPRVPNSDQKDSDGDGIGDACDNCPQKSNPDQADVDHDFVCDACDSD
Sequence
	QDQDGDGHQDSRDNCPTVPNSAQEDSDHDGQGDACDDDDDNDGVPDSRDNCRLVPNPGQEDADRDGVG
	DVCQDDFDADKVVDKIDACPENAEVTLTDFRAFQTVVLDPEGDAQIDPNWVVLNQGREIVQTMNSDPG
	LAVGYTAFNGVDFEGTFHVNTVTDDDYAGFIFGYQDSSSFYVVMWKQMEQTYWQANPFRAVAEPGIQL
	KAVKSSTGPGEQLRNALWHTGDTESQVRLLWKDPRNVGWKDKKSYRWFLQHRPQVGYIRVRFYEGPEL
	VADSNVVLDTTMRGGRLGVFCFSQENIIWANLRYRCNDTIPEDYETHQLRQALE
	SEQ ID NO:33	1386 bp
NOV3k,	AGATCTCAQGAGGATGTGGACCGCGATGGCATCGGAGACGCCTGCGATCCGGATGCCGACGGGGACG
248644823
DNA Sequence	CGGTCCCCAATGAAAAGGACAACTGCCCGCTGGTGCGGAACCCAGACCAGCGCAACACGGACGAGGA
	CAAGTGGGGCGATGCGTGCGACAACTGCCGGTCCCAGAAGAACCACGACCAAAAGGACACAGACCAG
	GACGGCCGGGGCGATGCGTGCGACGACGACATCGACGGCGACCGGATCCGCAACCAGGCCGACAACT
	GCCCTAGGGTACCCAACTCAGACCAGAAGCACAGTGATGGCCATGGTATAGGGGATGCCTCTCACAA
	CTGTCCCCAGAAGAGCAACCCCGATCAGGCGGATGTGGACCACGACTTTGTGGGAGATGCTTGTCAC
	AGCGATCAAGACCAGGATGGAGACGGACATCAGGACTCTCGGGACAACTGTCCCACGGTGCCTAACA
	GTGCCCAGGAGGACTCACACCACGATGGCCAGGGTCATGCCTGCGACGACGACGACGACAATGACGG
	AGTCCCTGACAGTCGGGACAACTGCCGCCTGGTGCCTAACCCCGGCCAGGAGGACGCGGACAGGGAC
	GGCGTCGGCGACGTGTGCCAGGACGACTTTGATGCACACAAGGTGGTAGACAAGATCGACGCGTGTC
	CGGAGAACGCTGAAGTCACGCTCACCGACTTCAGGGCCTTCCAGACAGTCGTGCTGGACCCGGAGGG
	TGACGCGCAGATTCACCCCAACTGGGTGGTGCTCAACCAGCGAACCGAGATCGTGCAGACAATCAAC
	AGCGACCCACGCCTGGCTGTGCGTTACACTGCCTTCAATGGCGTGCACTTCGAGGGCACGTTCCATG
	TGAACACGGTCACGGATGACGACTATGCGGGCTTCATCTTTGGCTACCAGGACAGCTCCAGCTTCTA
	CGTGGTCATGTGGAAGCAGATCGAGCAAACGTATTGGCAGGCCAACCCCTTCCGTGCTGTGGCCGAG
	CCTCGCATCCAACTCAAGGCTGTGAAGTCTTCCACAGGCCCCCGGOAACAGCTGCGGAACGCTCTGT
	GGCATACAGGAGACACAGAGTCCCAGGTGCCGCTCCTGTGGAAGGACCCGCGAAACGTGGGTTGGAA
	GGACAAGAAGTCCTATCGTTGGTTCCTGCAGCACCGGCCCCAAGTGGGCTACATCAGCGTGCGATTC
	TATGAGGGCCCTGAGCTGGTGGCCGACAGCAACGTGGTCTTGGACACAACCATGCGGGGTGGCCGCC
	TGGGGGTCTTCTGCTTCTCCCAGGAGAACATCATCTGCGCCAACCTGCGTTACCGCTGCAATGACAC
	CATCCCAGAGGACTATGAGACCCATCAGCTGCGGCAAGCCCTCGAG
	ORF Start: at 1		ORF Stop: end of sequence
	SEQ ID NO:34	462 aa	MW at 51565.6 kD
NOV3k,	RSQEDVDRDGIGDACDPDADGDGVPNEKDNCPLVRNPDQRNTDEDKWGDACDNCRSQKNDDQKDTDQ
248644823
Protein	DGRGDACDDDIDCDRIRNQADNCPRVPNSDQKDSDGDGIGDACDNCPQKSNPDQADVDHDFVGDACD
Sequence
	SDQDQDGDGHQDSRDNCPTVPNSAQEDSDHDGQGDACDDDDDNDGVPDSRDNCRLVPNPCQEDADRD
	GVGDVCQDDFDADKVVDKIDACPENAEVTLTDFRAFQTVVLDPEGDAQIDPNWVVLNQGREIVQTMN
	SDPGLAVGYTAFNGVDFEGTFHVNTVTDDDYAGFIFGYQDSSSFYVVMWKQMEQTYWQANPFRAVAE
	PGIQLKAVKSSTGPGEQLRNALWHTGDTESQVRLLWKDPRNVGWKDKKSYRWFLQHRPQVGYIRVRF
	YEGPELVADSNVVLDTTMRGGRLGVFCFSQENIIWANLRYRCNDTIPEDYETHQLRQALE
	SEQ ID NO:35	672 bp
NOV3l,	AAGCTTCACGAGGATGTGGACCGCGATGGCATCGGAGACGCCTGCGATCCGGATGCCGACGGGGACCG
248644900
DNA Sequence	GGTCCCCAATGAAAAGGACAACTGCCCGCTGGTGCGGAACCCAOACCAGCGCAACACGGACGAGGACA
	AGTGGCGCGATGCGTGCGACAACTGCCGGTCCCAGAAGAACGACGACCAAAAGGACACAGACCACGAC
	GGCCGGGGCGATGCGTGCGACGACGACATCGACGGCGACCGGATCCGCAACCAGGCCGACAACTGCCC
	TAGGGTACCCAACTCAOACCAGAAGGACAGTGATGGCGATGGTATAGGGGATGCCTGTGACAACTGTC
	CCCAGAAGAGCAACCCGGATCAGGCGGATGTGGACCACGACTTTGTGGGACATGCTTGTGACAGCGAT
	CAAGACCAGGATGGAGACGGACATCAGGACTCTCGGGACAACTGTCCCACGGTGCCTAACAGTGCCCA
	GGAGGACTCAGACCACGATGGCCAGGGTGATGCCTGCGACGACGACGACGACAATGACGGAGTCCCTG
	ACAGTCGGGACAACTGCCGCCTGGTGCCTAACCCCGGCCAGGAGGACGCGGACAGGGACGGCGTGGGC
	GACGTGTGCCAGGACGACTTTGATGCAGACAAGGTGGTAGACAAGATCCACGTGCTCGAG
	ORF Start: at 1		ORE Stop: end of sequence
	SEQ ID NO:36	224 aa	MW at 24274.4 kD
NOV3l,	KLQEDVDRDGIGDACDPDADGDGVPNEKDNCPLVRNPDQRNTDEDKWGDACDNCRSQKNDDQKDTDQD
248644900
Protein	CRGDACDDDIDGDRIRNQADNCPRVPNSDQKDSDGDGIGDACDNCPQKSNPDQADVDHDFVGDACDSD
Sequence
	QDQDGDGHQDSRDNCPTVPNSAQEDSDHDCQGDACDDDDDNDGVPDSRDNCRLVPNPGQEDADRDGVG
	DVCQDDPDADKVVDKIDVLE
	SEQ ID NO:37	2223 bp
NOV3m,	AAGCTTCACGGCCAGAGCCCGTTGGGCTCAGATCTGGQCCCGCAGATGCTTCGGGAACTGCAGGAAA
248576435
DNA Sequence	CCAACGCGGCGCTGCAGGACGTGCGGGAGCTGCTGCGGCAGCAGGTCAGGGAGATCACGTTCCTGAA
	AAACACGGTGATGGAGTGTGACCCGTGCGGGATGCAGCAGTCAGTACGCACCGGCCTACCCAGCGTG
	CGGCCCCTGCTCCACTGCGCGCCCGGCTTCTGCTTCCCCGGCGTGGCCTGCATCCAGACGGAGAGCG
	GCGCCCGCTGCGGCCCCTGCCCCGCCGGCTTCACCGGCAACGGCTCGCACTGCACCGACGTCAACGA
	GTGCAACGCCCACCCCTGCTTCCCCCGAGTCCGCTGTATCAACACCAGCCCGGCGTTCCGCTGCCAC
	GCTTGCCCGCCGGGTACAGCGGCCCCACCCACCAGGGCGTGGCGCTGGCTTTCGCCAAGGCCAACA
	AGCAGGTTTGCACGGACATCAACGAGTGTGAGACCGGGCAACATAACTGCGTCCCCAACTCCGTGTG
	CATCAACACCCGGGGCTCCTTCCAGTGCGGCCCGTGCCAGCCCGGCTTCGTGGGCGACCAGGCGTCC
	GGCTGCCAGCGGCGCGCACAGCGCTTCTGCCCCGACGGCTCGCCCAGCGAGTGCCACGAGCATGCAG
	ACTGCGTCCTAGAGCGCGATGGCTCGCGGTCGTGCGTGTGTCCCGTTGGCTCGGCCCGCAACGGGAT
	CCTCTGTGGTCGCGACACTGACCTAGACGGCITCCCGGACGAGAAGCTGCGCTGCCCGGAGCGCCAG
	TGCCGTAAGGACAACTGCGTGACTGTGCCCAACTCAGGGCAGGAGGATGTGGACCCCCATGGCATCG
	GAGACCCCTGCGATCCGGATGCCGACGGGCACGGCGTCCCCAATGAAAAGGACAACTGCCCGCTGGT
	GCGGAACCCAGACCAGCQCAACACGGACGAGQACAAGTGGGGCGATGCGTGCGACAACTGCCGGTCC
	CAGAAGAACGACGACCAAAAGGACACAGACCAGGACGGCCCGGGCGATGCGTGCGACGACGACATCG
	ACGGCGACCGCATCCCCAACCAGGCCGACAACTGCCCTAGGGTACCCAACTCAGACCAGAAGGACAG
	TGATGGcGATGGTATAGGGGATCCCTGTGACAACTGTCCCCAGAAGAGCAACCCGGATCAGGCGGAT
	GTGCACCACGACTTTGTGGGAGATGCTTGTGACAGCGATCAAGACCAGGATGGAGACGGACATCACG
	ACTCTCGGGACAACTGTCCCACGGTGCCTAACAGTGCCCAGGAGGACTCAGACCACGATGGCCAGGO
	TGATGCCTGCGACGACGACGACGACAATGACGGAGTCCCTGACAGTCGGGACAACTGCCGCCTGGTG
	CCTAACCCCGGCCAGGAGGACGCGGACAGGGACGGCGTGGGCGACGTGTGCCAGGACGACTTTGATG
	CAGACAAGGTGGTAGACAACATCGACGTGTGTCCGGAGAACCCTGAAGTCACGCTCACCGACTTCAG
	GGCCTTCCAGACAGTCGTGCTGGACCCGGAGCGTGACGCGCAGATTGACCCCAACTGGGTGGTGCTC
	AACCAGGGAAGGGAGATCGTGCAGACAATGAACAGCGACCCAGGCCTGGCTGTGGGTTACACTGCCT
	TCAATGGCGTGGACTTCCAGGGCACGTTCCATGTGAACACGGTCACCGATGACGACTATGCGGGCTT
	CATCTTTGGCTACCAGGACAGCTCCAGCTTCTACGTGGTCATGTGGAAGCAGATGGAGCAAACGTAT
	TGGCAGGCGAACCCCTTCCGTGCTGTGGCCGAGCCTGGCATCCAACTCAAGGCTGTGAAGTCTTCCA
	CAGGCCCCGGGGAACAGCTGCGGAACGCTCTGTGGCATACAGGAGACACAQAGTCCCAGGTGCGGCT
	CCTGTGGAAGGACCCGCGAAACGTGGGTTCGAAGGACAAGAAGTCCTATCGTTGGTTCCTGCAGCAC
	CGGCCCCAAGTCGGCTACATCACGGTGCGATTCTATGAGGQCCCTGAGCTGGTGGCCGACAGCAACG
	TGGTCTTGGACACAACCATGCGGGGTGGCCGCCTGGGCGTCTTCTGCTTCTCCCAGGAGAACATCAT
	CTGCGCCAACCTGCGTTACCGCTGCAATGACACCATCCCAGAGGACTATGAGACCCATCAGCTGCGG
	CAAGCCCTCGAG
	ORF Start: at 1		ORF Stop: end of sequence
	SEQ ID NO:38	741 aa	MW at 81445.0 kD
NOV3m,	KLQGQSPLGSDLGPQMLRELQETNAALQDVRELLRQQVREITFLKNTVMECDACGMQQSVRTGLPSV
248576435
Protein	RPLLHCAPGFCFPGVACIQTESQARCGPCPAGFTGNGSHCTDVNECNAHPCFPRVRCINTSPGFRCE
Sequence
	ACPPGYSGPTHQGVGLAFAKANKQVCTDINECETGQHNCVPNSVCINTRGSFQCGPCQPGFVGDQAS
	GCQRRAQRFCPDGSPSECHEHADCVLERDGSRSCVCAVGWAGNGILCGRDTDLDGFPDEKLRCPERQ
	CRKDNCVTVPNSGQEDVDRDGIGDACDPDADGDGVPNEKDNCPLVRNPDQRNTDEDKWGDACDNCRS
	QKNDDQKDTDQDGRGDACDDDIDGDRIRNQADNCPRVPNSDQKDSDGDGIGDACDNCPQKSNPDQAD
	VDHDFVGDACDSDQDQDGDGHQDSRDNCPTVPNSAQEDSDHDGQGDACDDDDDNDGVPDSRDNCRLV
	PNPGQEDADRDGVGDVCQDDFDADKVVDKIDVCPENAEVTLTDFRAFQTVVLDPEGDAQIDPNWVVL
	NQGREIVQTMNSDPGLAVGYTAFNGVDFEGTFHVNTVTDDDYAGFIFGYQDSSSFYVVMWKQMEQTY
	WQANPPRAVAEPGIQLKAVKSSTGPGEQLRNALWHTGDTESQVRLLWKDPRNVGWKDKKSYRWFLQH
	RPQVGYIRVRPYEGPELVADSNVVLDTTMRGGRLGVFCFSQENIIWANLRYRCNDTIPEDYETHQLR
	QALE
	SEQ ID No:39	2296 bp
NOV3n,	CACCAAGCTTCCCACCATGGTCCCCGACACCGCCTGCGTTCTTCTGCTCACCCTGGCTGCCCTCGGC
310681505
DNA Sequence	GCGTCCGGACAGGGCCAGAGCCCGTTGGGCTCAGACCTGGGCCCGCAGATGCTTCGGGAACTGCACG
	AAACCAACGCGGCGCTGCAGGACGTGCGQGAGCTGCTGCGGCAGCAGGTCAGGGAGATCACGTTCCT
	GAAAAACACGGTGATGGAGTGTGACGCGTGCGCGATGCAGCAGTCAGTACGCACCGGCCTACCCAGC
	GTGCGGCCCCTGCTCCACTGCGCGCCCGGCTTCTGCTTCCCCGGCGTGGCCTGCATCCAGACGGAGA
	GCGGCGCGCGCTGCGGCCCCTGCCCCGCGGGCTTCACGGGCAACGGCTCQCACTGCACCQACGTCAA
	CGAGTGCAACGCCCACCCCTGCTTCCCCCGAGTCCGCTGTATCAACACCAGCCCGGCGTTCCGCTGC
	GAGGCTTGCCCGCCCGGGTACAGCGGCCCCACCCACCAGGGCGTGGGGCTGCCTTTCGCCAAGGCCA
	ACAAGCAGGTTTGCACGGACATCAACGAGTGTGAGACCGGGCAACATAACTGCGTCCCCAACTCCGT
	GTGCATCAACACCCGGGGCTCCTTCCAGTGCGGCCCGTGCCAGCCCCGCTTCGTCGGCGACCAGGCG
	TCCGCCTGCCAGCGGCGCGCACAQCGCTTCTGCCCCGACGGCTCGCCCAGCGAGTGCCACGAGCATG
	CAGACTGCGTCCTAGAGCGCGATGGCTCGCGGTCGTGCGTGTGTGCCGTTGGCTGGGCCGGCAACGG
	GATCCTCTGTGGTCGCGACACTGACCTAGACGGCTTCCCGGACGAGAAGCTGCGCTGCCCGGAGCGC
	CAGTGCCGTAAGGACAACTGTGTGACTGTGCCCAACTCAGGGCACGAGGATGTGGACCGCGATGGCA
	TCGGAGACGCCTGCGATCCGCATGCCGACGGGGACGGGGTCCCCAATGAAAAGGACAACTGCCCGCT
	GGTGCGGAACCCAGACCAGCGCAACACGCACGAGGACAAGTGGGGCGATGCGTGCGACAACTGCCGG
	TCCCAGAAGAACGACGACCAAAAGGACACAGACCAGGACGGCCGGGGCGATCCGTGCCACGACGACA
	TCGACGGCGACCGGATCCGCAACCAGGCCGACAACTGCCCTAGGGTACCCAACTCAGACCAGAAGGA
	CAGTGATGGCGATGGTATAGGGGATGCCTGTGACAACTGTCCCCAGAAGAGCAACCCCGATCAGGCG
	GATGTGGACCACGACTTTGTGCGAGATGCTTGTGACAGCGATCAAGACCAGGATGGAGACGGACATC
	AGGACTCTCGGGACAACTGTCCCACGGTGCCTAACAGTGCCCAGGAGGACTCAGACCACGATGGCCA
	GGGTGATGCCTGCGACGACGACGACGACAATGACGCAGTCCCTGACAGTCGGGACAACTGCCGCCTG
	GTCCCTAACCCCGGCCACGAGGACGCGGACAGCGACGGCGTCGGCGACGTGTGCCAGCACGACTTTG
	ATGCACACAACCTGGTAGACAAGATCGACGTGTGTCCGGAGAACGCTGAAGTCACGCTCACCGACTT
	CAGGGCCTTCCAGACAGTCGTGCTGGACCCGGAGGGTGACGCGCAGATTGACCCCAACTGGGTGGTG
	CTCAACCAGGGAAGOGAGATCGTGCAGACAATGAACAGCGACCCAGGCCTGGCTGTGCGTTACACTG
	CCTTCAATGGCGTGGACTTCGAGGGCACGTTCCATGTGAACACCGTCACGGATGACGACTATGCGGG
	CTTCATCTTTGGCTACCAGGACAGCTCCAGCTTCTACQTGGTCATGTGGAAGCAGATGGAGCAAACG
	TATTGGCAGGCGAACCCCTTCCGTGCTGTGGCCGAGCCTGGCATCCAACTCAAGGCTGTGAAGTCTT
	CCACAGGCCCCGGGGAACAGCTGCGGAACGCTCTQTGGCATACACGAGACACAGAGTCCCAGGTGCG
	GCTGCTGTGGAAGGACCCGCGAAACGTGGGTTGGAAGCACAAGAAGTCCTATCGTTGGTTCCTGCAG
	CACCGGCCCCAAGTGGGCTACATCAGGGTGCGATTCTATGAGGGCCCTGAGCTGGTGGCCGACAGCA
	ACGTCGTCTTGGACACAACCATGCGGGGTGGCCGCCTCGGGGTCTTCTGCTTCTCCCAGGAGAACAT
	CATCTGGGCCAACCTGCGTTACCGCTGCAATGACACCATCCCAGAGGACTATGAGACCCATCAGCTG
	CGGCAAGCCCTCGAGGGC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO:40	765 aa	MW at 83699.6 kD
NOV3n,	TKLPTMVPDTACVLLLTLAALCASGQGQSPLGSDLGPQMLRELQETNAALQDVRELLRQQVREITEL
310681505
Protein	KNTVMECDACGMQQSVRTGLPSVRPLLHCAPGFCFPQVACIQTESGARCGPCPACFTGNGSHCTDVN
Sequence
	ECNAHPCFPRVRCINTSPGFRCEACPPGYSGPTHQGVGLAFAKANKQVCTDINECETCQHNCVPNSV
	CINTRGSFQCGPCQPQFVGDQASGCQRRAQRFCPDGSPSECHEHADCVLERDGSRSCVCAVCWAGNG
	ILCGRDTDLDGFPDEKLRCPERQCRKDNCVTVPNSGQSDVDRDGIGDACDPDADGDGVPNEKDNCPL
	VRNPDQRNTDEOKWGDACDNCRSQKNDDQKDTDQDGRCDACDDDIDGDRIRNQADNCPRVPNSDQKD
	SDGDGIGDACDNCPQKSNPDQADVDHDFVGDACDSDQDQDGDGHQDSRDNCPTVPNSAQEDSDHDCQ
	GDACDDDDDNDGVPDSRDNCRLVPNPGQEDADRDGVGDVCQDDFDADKVVDKIDVCPENAEVTLTDF
	RAFQTVVLDPEGDAQIDPNWVVLNQGREIVQTMNSDPGLAVGYTAFNGVDFEGTFHVNTVTDDDYAG
	FIFGYQDSSSFYVVMWKQMEQTYWQANPFRAVAEPGIQLKAVKSSTGPGEQLRNALWHTGDTESQVR
	LLWKDPRNVGWKDKKSYRWFLQHRPQVGYIRVRFYEGPELVADSNVVLDTTMRGGRLGVFCFSQENI
	IWANLRYRCNDTIPEDYETHQLRQALEG
	SEQ ID NO:41	2223 bp
NOV3o,	AAGCTTCAGGGCCAGAGCCCGTTGGGCTCAGATCTGGGCCCQCAGATGCTTCGGGAACTGCAGGAAA
CG105716-07
DNA Sequence	CCAACCCGGCGCTGCAGGACGTGCGGGAGCTGCTGCGCCAGCAGGTCAGGGAGATCACGTTCCTGAA
	AAACACCGTGATGGAGTGTGACGCCTCCGGGATGCAQCAQTCAGTACGCACCGGCCTACCCAGCGTG
	CGGCCCCTGCTCCACTGCGCGCCCGGCTTCTGCTTCCCCGGCGTGGCCTGCATCCAGACGGAGAGCG
	GCGCGCGCTGCGGCCCCTGCCCCGCGGGCTTCACGGGCAACGGCTCGCACTGCACCGACGTCAACGA
	GTGCAACGCCCACCCCTGCTTCCCCCGAGTCCGCTGTATCAACACCAGCCCCOGGTTCCGCTGCGAG
	GCTTGCCCCCCGGGGTACAGCGGCCCCACCCACCACGGCGTGGGGCTGGCTTTCGCCAAGGCCAACA
	AGCAGCTTTGCACGGACATCAACGAGTGTGAGACCGQGCAACATAACTGCGTCCCCAACTCCGTGTG
	CATCAACACCCGQGGCTCCTTCCAGTGCGGCCCGTGCCAGCCCCGCTTCGTGGGCGACCAGGCGTCC
	GGCTGCCAGCGGCGCGCACAGCGCTTCTGCCCCGACGGCTCGCCCAQCGAGTGCCACGAQCATGCAG
	ACTGCGTCCTAGAGCQCGATGGCTCCCGGTCGTGCGTGTGTGCCGTTGGCTCGGCCGGCAACCGGAT
	CCTCTGTGGTCGCCACACTGACCTAGACGGCTTCCCGGACGAGAAGCTGCGCTGCCCGGAGCGCCAG
	TGCCGTAAGGACAACTGCGTGACTGTGCCCAACTCAGGGCAGGAGGATGTGGACCGCGATGGCATCG
	GAGACGCCTGCGATCCGGATGCCGACGGGGACGGGGTCCCCAATGAAAACGACAACTGCCCGCTCGT
	GCGGAACCCAGACCAGCGCAACACGGACGACGACAAGTCGGGCGATGCGTGCGACAACTGCCGGTCC
	CAGAAGAACGACGACCAAAAGGACACAGACCACGACGGCCGGGGCGATQCGTGCGACGACGACATCG
	ACGGCGACCGGATCCGCAACCAGGCCGACAACTGCCCTAGGGTACCCAACTCAGACCAGAAGGACAG
	TGATGGCGATGGTATAGGGGATGCCTGTGACAACTGTCCCCAGAAGAGCAACCCGGATCAGGCGCAT
	GTGGACCACGACTTTGTGGGAGATGCTTGTGACAGCGATCAAGACCAGGATGGAGACGGACATCAGG
	ACTCTCGGGACAACTGTCCCACGGTGCCTAACAGTGCCCAGGAGGACTCAGACCACGATGGCCAGGG
	TGATGCCTGCGACGACGACGACGACAATGACGGAGTCCCTGACAGTCGGGACAACTGCCGCCTGGTG
	CCTAACCCCGGCCAGGAGGACGCGGACAGCGACGGCGTGGGCGACGTGTGCCAGGACGACTTTGATG
	CAGACAAGGTGGTAGACAAGATCGACGTGTGTCCGGAGAACGCTGAAGTCACQCTCACCGACTTCAG
	GGCCTTCCAGACAGTCGTGCTGGACCCGGAGGGTGACGCGCAGATTGACCCCAACTGGGTGGTGCTC
	AACCACGGAAGGGAGATCGTGCAGACAATGAACAGCGACCCAGGCCTGGCTGTGGGTTACACTGCCT
	TCAATCGCGTGGACTTCGAGGGCACGTTCCATGTGAACACGGTCACGGATGACGACTATGCGGGCTT
	CATCTTTGGCTACCAGGACAGCTCCAGCTTCTACGTGGTCATGTGGAAGCAGATGGAGCAAACGTAT
	TCGCAGGCGAACCCCTTCCGTGCTGTGGCCGAGCCTGGCATCCAACTCAAGGCTGTGAAGTCTTCCA
	CAGGCCCCGGGGAACAGCTGCCGAACGCTCTGTGGCATACAGGAGACACAGAGTCCCAGGTGCGGCT
	GCTGTGGAAGGACCCGCGAAACGTGGGTTGGAAGGACAAGAAGTCCTATCGTTCGTTCCTGCAGCAC
	CGGCCCCAAGTGGGCTACATCAGGGTGCGATTCTATGAGGGCCCTGAGCTGGTGGCCGACAGCAACG
	TGGTCTTGCACACAACCATGCGGGGTGGCCGCCTGGGGGTCTTCTGCTTCTCCCAGGAGAACATCAT
	CTGGGCCAACCTGCGTTACCGCTGCAATGACACCATCCCAGAGGACTATGAGACCCATCAGCTGCCG
	CAAGCCCTCGAG
	ORF Start: at 7		ORF Stop: at 2218
	SEQ ID NO:42	737 aa	MW at 80961.4 kD
NOV3o,	QGQSPLGSDLGPQMLRELQETNAALQDVRELLRQQVREITFLKNTVMECDACGMQQSVRTGLPSVRP
CG105716-07
Protein	LLHCAPGFCFPGVACIQTESGARCGPCPAGFTGNGSHCTDVNECNAHPCFPRVRCINTSPQFRCEAC
Sequence
	PPGYSGPTHQGVGLAFAKANKQVCTDINECETGQHNCVPNSVCINTRGSFQCGPCQPGFVGDQASGC
	QRRAQRFCPDGSPSECHEHADCVLERDGSRSCVCAVGWAGNGILCGRDTDLDGFPDEKLRCPERQCR
	KDNCVTVPNSGQEDVDRDGIGDACDPDADGDGVPNEKLNCPLVRNPDQRMTDEDKWGDACDNCRSQK
	NDDQKDTDQDGRGDACDDDIDGDRIRNQADNCPRVPNSDQKDSDGDGIGDACDNCPQKSNPDQADVD
	HDFVGDACDSDQDQDGDGHQDSRDNCPTVPNSAQEDSDHDGQGDACDDDDDNDGVPDSRDNCRLVPN
	PGQEDADRDGVGDVCQDDFDADKVVDKIDVCPENAEVTLTDPRAFQTVVLDPEGDAQIDPNWVVLNQ
	GREIVQTMNSDPGLAVGYTAFNGVDFECTFHVNTVTDDDYAGFIFGYQDSSSFYVVMWKQMEQTYWQ
	ANPFRAVAEPGIQLKAVKSSTGPGEQLRNALWHTGDTESQVRLLWKDPRNVGWKDKKSYRWFLQHRP
	QVGYIRVRFYEGPELVADSNVVLDTTMRGGRLGVFCFSQENIIWANLRYRCNDTIPEDYETHQLRQA
	SEQ ID NO:43	2230 bp
NOV3p,	CACCAAGCTTCAGQGCCAGAGCCCGTTGGGCTCAGATCTGGGCCCGCAGATGCTTCGGGAACTGCAG
CG105716-08
DNA Sequence	GAAACCAACGCGGCGCTGCAGCACGTGCGGGAGCTGCTGCGGCAGCAGATCAGGGAGATCACGTTCC
	TGAAAAACACGGTGATGGAGTGTGACGCGTGCGGGATGCAGCAGTCAGTACGCACCGGCCTACCCAG
	CGTGCGGCCCCTGCTCCACTGCGCGCCCGGCTTCTGCTTCCCCGGCGTGCCCTGCATCCAGACGGAG
	AGCGGCGCGCGCTGCGGCCCCTGCCCCGCGGGCTTCACGGGCAACGGCTCGCACTGCACCGACGTCA
	ACGAGTGCAACGCCCACCCCTGCTTCCCCCGAGTCCGCTGTATCAACACCAGCCCGGCGTTCCGCTG
	CGAGGCTTCCCCGCCGGGGTACAGCGGCCCCACCCACCAGGGCGTQGGGCTGGCTTTCGCCAAGGCC
	AACAAGCAGGTTTGCACGGACATCAACGAGTGTGAGACCGCGCAACATAACTGCGTCCCCAACTCCG
	TGTGCATCAACACCCGGGGCTCCTTCCAGTGCGGCCCQTGCCAGCCCGGCTTCGTCGGCGACCAGGC
	GTCCGGCTGCCAGCGGCGCGCACAGCGCTTCTGCCCCGACGGCTCGCCCAGCGAGTGCCACGACCAT
	GCAGACTGCGTCCTAGAGCGCGATGGCTCGCGGTCGTGCGTGTGTGCCGTTGGCTGGGCCGGCAACG
	GGATCCTCTGTGCTCGCGACACTGACCTAGACGGCTTCCCGGACGAGAAGCTGCGCTGCCCGGACCG
	CCAGTGCCGTAAGGACAACTGCGTGACTGTGCCCAACTCACGGCAGGAGGATGTGGACCGCGATCCC
	ATCGGAGACGCCTGCGATCCGGATGCCGACGGGCACGGGGTCCCCAATGAAAAGGACAACTGCCCGC
	TGGTGCCGAACCCAGACCAGCGCAACACGGACGAGGACAAGTGGGGCGATGCGTGCGACAACTGCCG
	GTCCCAGAAGAACGACGACCAAAAGGACACACACCAGGACGGCCGGGGCGATGCGTGCGACGACGAC
	ATCGACCGCGACCCGATCCGCAACCAGGCCCACAACTGCCCTAGGGTACCCAACTCAGACCAGAAGG
	ACAGTGATGGCGATGGTATAGGGGATGCCTGTGACAACTGTCCCCAGAAGAGCAACCCGGATCAGGC
	GGATGTGOACCACGACTTTGTGGGAGATGCTTGTGACAGCQATCAAGACCAGGATGGAGACGOACAT
	CAGGACTCTCCGGACAACTGTCCCACGGTGCCTAACAGTGCCCAGCAGGACTCAGACCACGATGGCC
	ACGGTGATGCCTGCGACGACGACGACGACAATGACGGAGTCCCTGACAGTCGGGACAACTGCCGCCT
	GGTGCCTAACCCCGGCCAGCAGGACGCGGACAGGGACGGCQTGGGCGACGTGTGCCACGACGACTTT
	GATGCAGACAAGGTGGTAGACAAGATCGACGTGTGTCCGCAGAACGCTGAAGTCACGCTCACCGACT
	TCAGGGCCTTCCAGACAGTCGTGCTGGACCCGGAGGGTGACGCGCAGATTGACCCCAACTGGGTGGT
	GCTCAACCAGGGAAGGGAGATCGTGCAGACAATGAACAGCGACCCAGGCCTGGCTGTGGGTTACACT
	GCCTTCAATGGCGTGGACTTCGAGGGCACGTTCCATGTGAACACCGTCACGCATGACQACTATGCGG
	GCTTCATCTTTGGCTACCAGGACAGCTCCAGCTTCTACGTGGTCATGTGGAAGCAGATGGAGCAAAC
	GTATTGGCAGGCGAACCCCTTCCGTGCTGTGGCCGAGCCTCGCATCCAACTCAAGGCTGTGAAGTCT
	TCCACAGGCCCCOGCGAACAGCTGCGGAACGCTCTGTGGCATACAQGAGACACAQAGTCCCAGGTGC
	GGCTGCTGTCGAAGGACCCGCGAAACGTGGGTTGGAAGGACAAGAAGTCCTATCGTTGGTTCCTGCA
	GCACCGGCCCCAAGTGGGCTACATCAGGGTGCGATTCTATGAGGGCCCTGAGCTGGTGGCCAACAGC
	AACGTGGTCTTCGACACAACCATGCGGGGTGGCCCCCTCGGGGTCTTCTGCTTCTCCCAGGAGAACA
	TCATCTCGGCCAACCTGCGTTACCGCTGCAATGACACCATCCCAGACGACTATGAGACCCATCAGCT
	GCGGCAAGCCGTCGACGGC
	ORF Start: at 2		ORF Stop: end of sequence
	SEQ ID NO:44	743 aa	MW at 81575.1 kD
NOV3p,	TKLQGQSPLQSDLGPQMLRELQETNAALQDVRELLRQQVREITFLKNTVMECDACGMQQSVRTGLPS
CG105716-08
Protein	VRPLLHCAPGFCFPGVACIQTESGARCGPCPAGFTGNGSHCTDVNECNAHPCFPRVRCINTSPGFRC
Sequence
	EACPPGYSGPTHQGVQLAPAKANKQVCTDINECETGQHNCVPNSVCINTRGSFQCGPCQPGFVGDQA
	SGCQRRAQRFCPDGSPSECHEHADCVLERDGSRSCVCAVGWAQNGILCGRDTDLDGFPDEKLRCPER
	QCRKDNCVTVPNSGQEDVDRDGIGDACDPDADGDGVPNEKDNCPLVRNPDQRNTDEDKWGDACDNCR
	SQKNDDQKDTDQDGRGDACDDDIDGDRIRNQADNCPRVPNSDQKDSDCDGIGDACDNCPQKSNPDQA
	DVDHDFVGDACDSDQDQDGDGHQDSRDNCPTVPNSAQEDSDHDGQGDACDDDDDNDGVPDSRDNCRL
	VPNPGQEDADRDGVGDVCQDDFDADKVVDKIDVCPENAEVTLTDFRAFQTVVLDPEGDAQIDPNWVV
	LNQGREIVQTMNSDPGIAVGYTAFNGVDFEGTFHVNTVTDDDYAGFIFGYQDSSSFYVVMWKQMEQT
	YWQANPFRAVAEPGIQLKAVKSSTGPGEQLRNALWHTGDTESQVRLLWKLPRNVCWKDKKSYRWFLQ
	HRPQVGYIRVRFYEGPELVADSNVVLDTTMRGGRLGVFCFSQENIIWANLRYRCNDTIPEDYETHQL
	RQAVDG
	SEQ ID NO:45	2296 bp
NOV3q,	CACCAGATCTCCCACCATGGTCCCCGACACCGCCTGCGTTCTTCTGCTCACCCTGGCTGCCCTCGGC
CG105716-10
DNA Sequence	GCGTCCGGACAGGGCCAGAGCCCCTTGGGCTCAGACCTGGQCCCGCAGATGCTTCGGGAACTGCAGG
	AAACCAACGCGGCGCTGCAGGACGTGCGGGAGCTGCTGCGGCAGCAGGTCAGGGAGATCACGTTCCT
	CAAAAACACGGTGATGGAGTGTGACGCGTGCGCGATGCAGCAGTCAGTACGCACCGGCCTACCCAGC
	GTGCGGCCCCTGCTCCACTGCGCGCCCGGCTTCTGCTTCCCCGQCGTGGCCTGCATCCAGACGGAGA
	GCGGCGCGCGCTGCGGCCCCTGCCCCGCGGGCTTCACGGGCAACGGCTCGCACTGCACCGACGTCAA
	CGAGTGCAACGCCCACCCCTGCTTCCCCCCAGTCCGCTGTATCAACACCAGCCCGGGGTTCCGCTGC
	GAGGCTTGCCCGCCCGGGTACAGCGGCCCCACCCACCAGGGCGTGQQGCTGGCTTTCGCCAAGGCCA
	ACAAGCAGGTTTGCACGGACATCAACGAGTGTGAGACCGGGCAACATAACTGCGTCCCCAACTCCGT
	GTGCATCAACACCCCGGGCTCCTTCCAGTGCGGCCCGTGCCAGCCCOGCTTCGTGGGCCACCAGGCG
	TCCCGCTCCCAGCGGCGCGCACAGCGCTTCTGCCCCGACGGCTCGCCCAGCGAGTGCCACGAGCATG
	CAGACTGCGTCCTAGAGCQCGATGGCTCGCGGTCGTCCGTGTGTCCCGTTGGCTGGGCCGGCAACGG
	GATCCTCTGTGGTCGCGACACTGACCTAGACGGCTTCCCGGACGAGAAGCTGCGCTGCCCGGAGCGC
	CAGTGCCGTAAGGACAACTGTGTGACTGTGCCCAACTCAGGGCACGACGATGTGGACCGCGATGGCA
	TCGGAGACGCCTGCGATCCGGATGCCGACGGGGACGGGGTCCCCAATGAAAAGGACAACTGCCCGCT
	GGTGCGGAACCCAGACCAGCQCAACACGGACGAGGACAAGTCGGGCGATGCGTCCGACAACTGCCGG
	TCCCACAAGAACGACGACCAAAAGGACACAGACCAGGACGGCCGGGGCGATGCGTGCGACGACGACA
	TCGACGGCCACCGQATCCGCAACCAGGCCGACAACTGCCCTAGGGTACCCAACTCAGACCAGAACGA
	CAGTGATGGCGATGGTATACGCGATGCCTGTGACAACTGTCCCCAGAAGAGCAACCCGGATCAGGCG
	GATGTGGACCACGACTTTQTGGGAGATGCTTGTCACAGCQATCAAGACCAGGATGGAGACGGACATC
	AGGACTCTCGGGACAACTGTCCCACGGTGCCTAACAGTCCCCACGAGGACTCAGACCACGATGGCCA
	GGGTGATGCCTGCCACGACGACGACGACAATGACGGAGTCCCTCACAGTCGGGACAACTGCCGCCTG
	GTGCCTAACCCCQGCCAGGAGGACGCGGACAGGGACGGCGTCGGCCACGTGTGCCAGGACGACTTTG
	ATGCAGACAAGGTGGTAGACAAGATCCACGTGTQTCCGGAGAACGCTGAAGTCACGCTCACCGACTT
	CAGGGCCTTCCAGACAGTCGTGCTGQACCCCGAGGGTGACGCGCAGATTGACCCCAACTGCGTGGTG
	CTCAACCAGGGAAGCGAGATCGTGCAGACAATGAACAGCGACCCAGGCCTGGCTGTCGGTTACACTG
	CCTTCAATGGCGTGGACTTCGAGGGCACGTTCCATGTGAACACGGTCACGGATGACGACTATGCGGG
	CTTCATCTTTGGCTACCAGGACAGCTCCAGCTTCTACGTGCTCATGTGGAAGCAGATGGAGCAAACG
	TATTGGCAGGCGAACCCCTTCCGTGCTGTGGCCGAGCCTGGCATCCAACTCAAGGCTGTGAAGTCTT
	CCACAGGCCCCGGGGAACAGCTGCCGAACGCTCTGTGGCATACAGGAGACACAGAGTCCCAGGTGCG
	GCTGCTGTGGAAQGACCCGCGAAACGTGGGTTGGAAGGACAAGAAGTCCTATCGTTGGTTCCTGCAG
	CACCGGCCCCAAGTGGGCTACATCAGGGTGCGATTCTATGAGGGCCCTGAGCTGGTGGCCGACAGCA
	ACGTGGTCTTGGACACAACCATGCGGGGTGGCCGCCTGGGGGTCTTCTGCTTCTCCCAGGAGAACAT
	CATCTGGGCCAACCTGCGTTACCGCTGCAATGACACCATCCCAGAGGACTATGAGACCCATCAGCTG
	CGGCAAGCCCTCGAGGGC
	ORF Start: ATG at 17		ORF Stop: at 2288
	SEQ ID NO: 46	757 aa	MW at 82859.7 kD
NOV3q,	MVPDTACVLLLTLAALGASOQGQSPLCSDLGPQMLRELQEThAALQDVRELLRQQVREITFLKNTVM
CG105716-10
Protein	ECDACGMQQSVRTGLPSVRPLLHCAPGFCFPGVACIQTESGARCGPCPAGFTGNGSHCTDVNECNAH
Sequence
	PCFPRVRCINTSPGFRCEACPPGYSGPTHQGVGLAFAKANKQVCTDINECETGQHNCVPNSVCINTR
	GSFQCGPCQPOFVGDQASGCQRRAQRFCPDGSPSECHEHADCVLERDQSRSCVCAVCWAGNGILCGR
	DTDLDGFPDEKLRCPERQCRKDNCVTVPNSGQEDVDRDGIGDACDPDADGDGVPNEKDNCPLVRNPD
	QRNTDEDKWGDACDNCRSQKNDDQKDTDQDGRGDACDDDIDGDRIRNQADNCPRVPNSDQKDSDGDG
	IGDACDNCPQKSNPDQADVDHDFVGDACDSDQDQDGDGHQDSRDNCPTVPNSAQEDSDHDGQGDACD
	DDDDNDGVPDSRDNCRLVPNPGQEDADRDGVGDVCQDDFDADKVVDKIDVCPENAEVTLTDFRAFQT
	VVLDPEGDAQIDPNWVVLNQGREIVQTMNSDPGLAVGYTAFNGVDFEGTFHVNTVTDDDYAGFIFGY
	QDSSSFYVVMWKQMEQTYWQANPFRAVAEPGIQLKAVKSSTOPGEQLRNALWHTGDTESQVRLLWKD
	PRNVGWKDKKSYRWFLQHRPQVGYIRVRFYEGPELVADSNVVLDTTMRGGRLGVFCFSQENIIWANL
	RYRCNDTIPEDYETHQLRQA

[0379] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 3B.

TABLE 3B
Comparison of NOV3a against NOV3b through NOV3q.
	Protein	NOV3a Residues/	Identities/Similarities
	Sequence	Match Residues	for the Matched Region
	NOV3b	1..757	735/757 (97%)
		1..741	736/757 (97%)
	NOV3c	1..757	720/757 (95%)
		1..726	721/757 (95%)
	NOV3d	1..757	740/757 (97%)
		1..748	742/757 (97%)
	NOV3e	1..757	715/757 (94%)
		1..721	716/757 (94%)
	NOV3f	300..757	458/458 (100%)
		1..458	458/458 (100%)
	NOV3g	1..757	748/757 (98%)
		1..757	749/757 (98%)
	NOV3h	300..757	458/458 (100%)
		3..460	458/458 (100%)
	NOV3i	300..757	456/458 (99%)
		3..460	457/458 (99%)
	NOV3j	300..757	457/458 (99%)
		3..460	457/458 (99%)
	NOV3k	300..757	457/458 (99%)
		3..460	457/458 (99%)
	NOV3l	300..519	220/220 (100%)
		3..222	220/220 (100%)
	NOV3m	21..757	737/737 (100%)
		3..739	737/737 (100%)
	NOV3n	1..757	757/757 (100%)
		6..762	757/757 (100%)
	NOV3o	21..757	737/737 (100%)
		1..737	737/737 (100%)
	NOV3p	21..757	737/737 (100%)
		4..740	737/737 (100%)
	NOV3q	1..757	757/757 (100%)
		1..757	757/757 (100%)

[0380] Further analysis of the NOV3a protein yielded the following properties shown in Table 3C.

TABLE 3C
Protein Sequence Properties NOV3a
SignalP
analysis:	Cleavage site between residues 21 and 22
PSORT II	PSG:	a new signal peptide prediction method
analysis:		N-region:	length 4;	pos. chg 0;	neg. chg 1
		H-region:	length 24;	peak value	0.00
		PSG score:	−4.40
	GvH:	von Heijne's method for signal seq. recognition
		GvH score (threshold: −2.1): 3.65
		possible cleavage site: between 20 and 21
	>>> Seems to have no N-terminal signal peptide
	ALOM:	Klein et al's method for TM region allocation
		Init position for calculation: 1
		Tentative number of TMS(s) for the threshold 0.5: 1
		Number of TMS(s) for threshold 0.5: 0
		PERIPHERAL	Likelihood = 1.43 (at 87)
		ALOM score: −1.81 (number of TMSs: 0)
	MITDISC:	discrimination of mitochondrial targeting seq
		R content:	0	Hyd Moment (75):	7.90
		Hyd Moment (95):	5.39	G content:	4
		D/E content:	2	S/T content:	5
		Score: −7.28
	Gavel:	prediction of cleavage sites for mitochondrial preseq
		cleavage site motif not found
	NUCDISC:	discrimination of nuclear localization signals
		pat4: none
		pat7: none
		bipartite: none
		content of basic residues: 8.9%
		NLS Score: −0.47
	KDEL:	ER retention motif in the C-terminus: none
	ER Membrane Retention Signals: none
	SKL:	peroxisomal targeting signal in the C-terminus: none
	PTS2:	2nd peroxisomal targeting signal: none
	VAC:	possible vacuolar targeting motif: none
	RNA-binding motif: none
	Actinin-type actin-binding motif:
		type 1: none
		type 2: none
	NMYR:	N-myristoylation pattern: none
	Prenylation motif: none
	memYQRL:	transport motif from cell surface to Golgi: none
	Tyrosines in the tail: none
	Dileucine motif in the tail: none
	checking 63 PROSITE DNA binding motifs: none
	checking 71 PROSITE ribosomal protein motifs: none
	checking 33 PROSITE prokaryotic DNA binding motifs: none
	NNCN:	Reinhardt's method for Cytoplasmic/Nuclear discrimination
		Prediction: nuclear
		Reliability: 70.6
	COIL:	Lupas's algorithm to detect coiled-coil regions
	32 Q	0.97
	33 M	0.97
	34 L	0.97
	35 R	0.97
	36 E	0.97
	37 L	0.97
	38 Q	0.97
	39 E	0.97
	40 T	0.97
	41 N	0.97
	42 A	0.97
	43 A	0.97
	44 L	0.97
	45 Q	0.97
	46 D	0.97
	47 V	0.97
	48 R	0.97
	49 E	0.97
	50 L	0.97
	51 L	0.97
	52 R	0.97
	53 Q	0.97
	54 Q	0.97
	55 V	0.97
	56 R	0.97
	57 E	0.97
	58 I	0.97
	59 T	0.97
	60 F	0.97
	61 L	0.97
	62 K	0.97
	63 N	0.97
	64 T	0.84
	65 V	0.73
	total: 34 residues
	Final Results (k = 9/23):
	56.5%:	nuclear
	17.4%:	mitochondrial
	13.0%:	extracellular, including cell wall
	8.7%:	cytoplasmic
	4.3%:	peroxisomal
	>> prediction for CG105716-09 is nuc (k = 23)

[0381] 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/
	Protein/Organism/	Residues/	Similarities for	Ex-
Geneseq	Length	Match	the Matched	pect
Identifier	[Patent #, Date]	Residues	Region	Value
ABJ05594	Breast cancer-	1..757	751/757 (99%)	0.0
	associated protein	1..757	752/757 (99%)
	59-Unidentified,
	757 aa.
	[WO200259377-A2,
	1 AUG. 2002]
AAB00044	Human cartilage	1..757	750/757 (99%)	0.0
	oligomeric matrix	1..757	751/757 (99%)
	protein (COMP)-
	Homo sapiens, 757 aa.
	[WO200044908-A2,
	3 AUG. 2000]
AAR56248	Xenopus	29..756	516/740 (69%)	0.0
	thrombospondin-4-	150..886	602/740 (80%)
	Xenopus laevis, 889
	aa. [WO9413794-A,
	23 JUN. 1994]
AAE25032	Human	16..753	518/752 (68%)	0.0
	thrombospondin	211..952	598/752 (78%)
	(TSP)-4 protein-
	Homo sapiens, 961 aa.
	[WO200239122-A2,
	16 MAY 2002]
AAR56249	Human	16..753	518/752 (68%)	0.0
	thrombospondin-4-	211..952	598/752 (78%)
	Homo sapiens, 961 aa.
	[WO9413794-A,
	23 JUN. 1994]

[0382] 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	Identities/
Protein	Protein/	Residues/	Similarities for	Ex-
Accession	Organism/	Match	the Matched	pect
Number	Length	Residues	Portion	Value
P49747	Cartilage oligomeric	1..757	751/757 (99%)	0.0
	matrix protein	1..757	752/757 (99%)
	precursor (COMP)-
	Homo sapiens
	(Human), 757 aa.
O14592	COMP_HUMAN-	1..742	742/742 (100%)	0.0
	Homo sapiens	1..742	742/742 (100%)
	(Human), 817 aa.
Q8N4T2	Similar to cartilage	34..757	724/724 (100%)	0.0
	oligomeric matrix	1..724	724/724 (100%)
	protein
	(pseudoachondro-
	plasia,
	epiphyseal dysplasia 1,
	multiple)-Homo
	sapiens (Human),
	724 aa.
Q9BG80	Cartilage oligomeric	1..757	699/757 (92%)	0.0
	matrix protein-Equus	1..755	717/757 (94%)
	caballus (Horse),
	755 aa.
P35444	Cartilage oligomeric	5..757	686/753 (91%)	0.0
	matrix protein	4..755	711/753 (94%)
	precursor (COMP)-
	Rattus norvegicus
	(Rat), 755 aa.

[0383] PFam analysis predicts that the NOV3a protein contains the domains shown in the Table 3F.

TABLE 3F
Domain Analysis of NOV3a
		NOV3a	Identities/	Ex-
	Pfam	Match	Similarities for	pect
	Domain	Region	the Matched Region	Value
	EGF	229..266	10/47 (21%)	0.007
			30/47 (64%)
	tsp_3	300..314	11/15 (73%)	0.02
			13/15 (87%)
	tsp_3	336..350	9/15 (60%)	0.057
			15/15 (100%)
	tsp_3	359..373	10/15 (67%)	0.22
			15/15 (100%)
	tsp_3	395..409	12/15 (80%)	0.014
			15/15 (100%)
	tsp_3	418..432	10/15 (67%)	0.042
			13/15 (87%)
	tsp_3	456..470	12/15 (80%)	0.25
			15/15 (100%)
	tsp_3	492..506	10/15 (67%)	0.2
			14/15 (93%)

Example 4

[0384] 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:47	839 bp
NOV4a,	CAGATTTCCCTGTCAACCACGACGAGTCCAGAGAGGAAACGCGGAGCGGAGACAACAGTACCTGACGC
CG153910-01
DNA Sequence	CTCTTTCAGCCCGGGATCGCCCCAGCAGGGATGGGCGACAAGATCTGGCTGCCCTTCCCCGTGCTCCT
	TCTGGCCGCTCTGCCTCCGQTGCTGCTGCCTGGGGCGGCCGGCTTCACACCTTCCCTCGATAGCGACT
	TCACCTTTACCCTTCCCGCCQGCCAGACGGAGTGCTTCTACCAGCCCATCCCCCTGAAGGCCTCGCTG
	GAGATCGAGTACCAAGTTTTAGATGGAGCAGGATTAGATATTGATTTCCATCTTGCCTCTCCAGAAGG
	CAAAACCTTAGTTTTTGAACAAAGAAAATCAGATGGAGTTCACACTGTAGAGACTGAAGTTCGTGATT
	ACATGTTCTGCTTTQACAATACATTCAGCACCATTTCTGAGAAGGTGATTTTCTTTGAATTAATCCTG
	GATAATATGGGAGAACAGGCACAAGAACAAGAAGATTGGAAGAAATATATTACTGGCACAGATATATT
	GGATATGAAACTGGAAGACATCCTGGAATCCATCAACAGCATCAAGTCCAGACTAAGCAAAAGTGGGC
	ACATACAAATTCTGCTTAGAGCATTTGAAGCTCGTGATCGAAACATACAAGAAAGCAACTTTGATAGA
	GTCAATTTCTGGTCTATGGTTAATTTAGTGGTCATGGTGGTGGTGTCAGCCATTCAAGTTTATATGCT
	GAAGAGTCTGTTTGAAGATAAGAGGAAAAGTAGAACTTAA+E,UUNS AACTCCAAACTAGAGTACGTAACATTGA
	AAAATGAGGCATAAAAATGCAAT
	ORF Start: ATG at 99		ORF Stop: TAA at 786
	SEQ ID NO:48	229 aa	MW at 25989.5 kD
NOV4a,	MGDKIWLPFPVLLLAALPPVLLPGAAGFTPSLDSDFTFTLPAGQTECPYQPMPLKASLEIEYQVLDGA
CG153910-01
Protein	GLDIDFHLASPEGKTLVFEQRKSDGVHTVETEVCDYMFCFDNTFSTISEKVIFFELILDNMGEQAQEQ
Sequence
	EDWKKYITGTDILDMKLEDILESINSIKSRLSKSGHIQILLRAFEARDRNIQESNFDRVNFWSMVNLV
	VMVVVSAIQVYIVILKSLPEDKRRSRT
	SEQ ID NO: 49	1223 bp
NOV4b,	CAGTCGCTCACCACCCAAATCGTCGCTGGGAGAGACCAACCCGGCGACTGCGCGCTTCGCACTCGAG
CG153910-02
DNA Sequence	TCTGCGTTAGGAAGCCTCTGACCCTTTCCCGGGCCCCTGCGCGTGCAACCCTCGGACACAACTCGCA
	GAACCAGCGAACCCCGGCAGCACAGAATTCGAACCGCCGCGGGAGCCGTTGGGACGCGCCTACCCGG
	TCACTGTCCCGCCCCGGCGCAGACTGCGTGAGGCGCCGCCGAAGGCGCGGGGCTTGCCGGGCATCGT
	GGTCGGCGAGCGCGCCCGAGCCCACTAGCGGAGCCCGCCCGGGACTACATTTCCCACAATTACCGCC
	ATCATGCCCATTGGTQGGGCAAGCCATGGGAACCCGAGGCCGTCAGGGGGAGAGGCGGGCGGCGCTC
	ACGCCTGGCCTGAGCGCGCCGAGACTGAGGCGGTTGCCGAATAGGACTGCTAGCCCCGCCCAGAGTC
	CCTACCCTTTGGAGAACTGCGCTTCTCTTTCGGAGGGAGTGTTCGCCGCCGCCCCGGCCGCCACCTG
	GAGTTTCTTCAGACTCCAGATTTCCCTGTCAACCACCAGCAGTCCAGAGACGAAACGCGGAGCGCAG
	ACAACAGTACCTCACCCCTCTTTCAGCCCGGGATCGCCCCAGCAGGGATGGGCGACAAGATCTGCCT
	GCCCTTCCCCGTGCTCCTTCTGGCCGCTCTGCCTCCGGTGCTCCTGCCTCGGGCGGCCGGCTTCACA
	CCTTCCCTCGATAGCCACTTCACCTTTACCCTTCCCGCCGQCCAGAAQGAGTGCTTCTACCAGCCCA
	TGCCCCTCAAGGCCTCGCTGGAGATCGAGTACCAAGTTTTAGATGGAGCAGCATTAGATATTGATTT
	CCATCTTGCCTCTCCAGAAGGCAAAACCTTAGTTTTTGAACAAAGAAAATCAGATGGAGTTCACACT
	GTAGAGACTGAAGTTGGTGATTACATGTTCTGCTTTGACAATACATTCAGCACCATTTCTGAGAAGG
	TGATTTTCTTTGAATTAATCCTGGATAATATGCGAGAACACGCACAAGAACAAGAAGATTGGAAGAA
	ATATATTACTGGCACAGATATATTGGATATCAAACTGGAACACATCCTGCTCAGTATGGTCTTCTAA
	TAAAATAAAAATTATTAACAGCCACAGGCCTTACTATGGTAATAAGTTACTGAACTAACCATTTTAT
	CTGCATTATCCAGGAAA
	ORF Start: ATG at 651		ORF Stop: TAA at 1137
	SEQ ID NO:50	162 aa	MW at 18167.6 kD
NOV4b,	MGDKIWLPFPVLLLAALPPVLLPGAAGETPSLDSDFTFTLPAGQKECFYQPMPLKASLEIEYQVLDG
CG153910-02
Protein	AGLDIDFHLASPEGKTLVFEQRKSDGVHTVETEVGDYMFCFDNTFSTISEKVIFFELILDNMGEQAQ
Sequence
	EQEDWKKYITGTDILDMKLEDILVSMVF
	SEQ ID NO:51	712 bp
NOV4c,	CACCGGATCCACCATGGGCGACAAGATCTCGCTGCCCTTCCCCGTGCTCCTTCTGGCCGCTCTGCCTC
CG153910-03
DNA Sequence	CGGTGCTGCTGCCTCGGGCGGCCGGCTTCACACCTTCCCTCGATAGCGACTTCACCTTTACCCTTCCC
	GCCGGCCAGAAGGAGTGCTTCTACCAGCCCATGCCCCTGAAGGCCTCGCTGGAGATCGAGTACCAAGT
	TTTAGATGGAGCAGOATTACATATTGATTTCCATCTTGCCTCTCCAGAAGGCAAAACCTTAGTTTTTG
	AACAAAGAAAATCAGATGGAQTTCACACTGTAGAGACTGAAGTTGGTCATTACATGTTCTGCTTTGAC
	AATACATTCAGCACCATTTCTGAGAAGGTGATTTTCTTTGAATTAATCCTGGATAATATGGGAGAACA
	GGCACAAGAACAAGAAGATTGGAAGAAATATATTACTGGCACAGATATATTGGATATGAAACTGGAAG
	ACATCCTGGAATCCATCAACAGCATCAAGTCCAGACTAAGCAAAAGTGCGCACATACAAATTCTGCTT
	AGAGCATTTGAAGCTCGTGATCGAAACATACAAGAAAGCAACTTTGATAGAGTCAATTTCTGGTCTAT
	GGTTAATTTAGTGGTCATGGTGGTGGTGTCAGCCATTCAAGTTTATATGCTGAAGAGTCTGTTTGAAG
	ATAACAGGAAAAGTAGAACTTAGGTCGACGGC
	ORF Start: ATG at 14		ORF Stop: TAG at 701
	SEQ ID NO:52	229 aa	MW at 29016.6 kD
NOV4c,	MGDKIWLPFPVLLLAALPPVLLPGAAGFTPSLDSDFTFTLPAGQKECPYQPMPLKASLEIEYQVLDGA
CG153910-03
Protein	GLDIDFHLASPEGKTLVFEQRKSDGVHTVETEVGDYMPCFDNTFSTISEKVIFFELILDNMGEQAQEQ
Sequence
	EDWKKYITGTDILDMKLEDILESINSIKSRLSKSGHIQILLRAFEARDRNIQESNFDRVNPWSMVNLV
	VMVVVSAIQVYMLKSLFEDKRKSRT

[0385] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 4B.

TABLE 4B
Comparison of NOV4a against NOV4b and NOV4c.
		NOV4a Residues/	Identities/Similarities
	Protein Sequence	Match Residues	for the Matched Region
	NOV4b	1..160	157/160 (98%)
		1..160	158/160 (98%)
	NOV4c	1..229	228/229 (99%)
		1..229	228/229 (99%)

[0386] Further analysis of the NOV4a protein yielded the following properties shown in Table 4C.

TABLE 4C
Protein Sequence Properties NOV4a
SignalP
analysis:	Cleavage site between residues 28 and 29
PSORT II	PSG:	a new signal peptide prediction method
analysis:		N-region:	length 4;	pos. chg 1;	neg. chg 1
		H-region:	length 28;	peak value	9.26
		PSG score:	4.86
	GvH:	von Heijne's method for signal seq. recognition
		GvH score (threshold: −2.1): −0.04
		possible cleavage site: between 23 and 24
	>>> Seems to have a cleavable signal peptide (1 to 23)
	ALOM:	Klein et al's method for TM region allocation
		Init position for calculation: 24
		Tentative number of TMS(s) for the threshold 0.5: 1
		Number of TMS(s) for threshold 0.5: 1
		INTEGRAL	Likelihood = −5.89	Transmembrane 201-217
		PERIPHERAL	Likelihood = 5.62 (at 110)
		ALOM score: −5.89 (number of TMSs: 1)
	MTOP:	Prediction of membrane topology (Hartmann et al.)
		Center position for calculation: 11
		Charge difference: −4.0 C(−3.0) − N(1.0)
		N >= C: N-terminal side will be inside
	>>> membrane topology: type 1a (cytoplasmic tail 218 to 229)
	MITDISC:	discrimination of mitochondrial targeting seq
		R content:	0	Hyd Moment (75):	11.31
		Hyd Moment (95):	8.32	G content:	3
		D/E content:	2	S/T content:	2
		Score: −6.89
	Gavel:	prediction of cleavage sites for mitochondrial preseq
		cleavage site motif not found
	NUCDISC:	discrimination of nuclear localization signals
		pat4: none
		pat7: none
		bipartite: none
		content of basic residues: 9.2%
		NLS Score: −0.47
	KDEL:	ER retention motif in the C-terminus: none
		ER Membrane Retention Signals:
		KKXX-like motif in the C-terminus: RKSR
	SKL:	peroxisomal targeting signal in the C-terminus: none
	PTS2:	2nd peroxisomal targeting signal: none
	VAC:	possible vacuolar targeting motif: none
	RNA-binding motif: none
	Actinin-type actin-binding motif:
		type 1: none
		type 2: none
	NMYR:	N-myristoylation pattern: none
	Prenylation motif: none
	memYQRL:	transport motif from cell surface to Golgi: none
	Tyrosines in the tail: none
	Dileucine motif in the tail: none
	checking 63 PROSITE DNA binding motifs: none
	checking 71 PROSITE ribosomal protein motifs: none
	checking 33 PROSITE prokaryotic DNA binding motifs: none
	NNCN:	Reinhardt's method for Cytoplasmic/Nuclear discrimination
		Prediction: cytoplasmic
		Reliability: 94.1
	COIL:	Lupas's algorithm to detect coiled-coil regions
		total: 0 residues
	Final Results (k = 9/23):
	44.4%:	endoplasmic reticulum
	22.2%:	Golgi
	11.1%:	plasma membrane
	11.1%:	vesicles of secretory system
	11.1%:	extracellular, including cell wall
	>> prediction for CG153910-01 is end (k = 9)

[0387] 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
		NOV3a	Identities/
	Protein/Organism/	Residues/	Similarities for	Ex-
Geneseq	Length	Match	the Matched	pect
Identifier	[Patent #, Date]	Residues	Region	Value
AAU12376	Human PRO733	1..229	228/229 (99%)	e−129
	polypeptide	1..229	228/229 (99%)
	sequence-Homo
	sapiens, 229 aa.
	[WO200140466-A2,
	7 JUN. 2001]
AAY94859	Human protein	1..229	228/229 (99%)	e−129
	clone HP02515-	1..229	228/229 (99%)
	Homo sapiens,
	229 aa.
	[WO200005367-A2,
	3 FEB. 2000]
AAB34734	Human secreted	1..229	228/229 (99%)	e−129
	protein encoded by	1..229	228/229 (99%)
	DNA clone vq20
	1-Homo sapiens,
	229 aa.
	[WO200055375-A1,
	21 SEP. 2000]
AAB44310	Human PRO733	1..229	228/229 (99%)	e−129
	(UNQ411) protein	1..229	228/229 (99%)
	sequence SEQ ID
	NO:447-Homo
	sapiens, 229 aa.
	[WO200053756-A2,
	14 SEP. 2000]
AAY41754	Human PRO733	1..229	228/229 (99%)	e−129
	protein sequence-	1..229	228/229 (99%)
	Homo sapiens,
	16 SEP. 1999]

[0388] 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
		NOV4a	Identities/
Protein		Residues/	Similarities for
Accession	Protein/	Match	the Matched	Expect
Number	Organism/Length	Residues	Portion	Value
Q9Y3A6	Protein CGI-100	1..229	227/229 (99%)	e−128
	precursor-Homo	1..229	227/229 (99%)
	sapiens (Human),
	229 aa.
Q9CXE7	4432412D15Rik	1..229	204/229 (89%)	e−115
	protein-Mus	1..229	215/229 (93%)
	musculus
	(Mouse), 229 aa.
Q8VCE7	RIKEN cDNA	1..229	203/229 (88%)	e−115
	4432412D15 gene-	1..229	215/229 (93%)
	Mus musculus
	(Mouse), 229 aa.
CAC22512	Sequence I from	1..158	153/158 (96%)	5e−85
	Patent WO0075321-	1..158	154/158 (96%)
	Cloning vector
	pINTI, 169 aa.
Q13445	Putative T1/ST2	17..225	120/210 (57%)	1e−62
	receptor binding	16..223	157/210 (74%)
	protein precursor-
	Homo sapiens
	(Human), 227 aa.

[0389] PFam analysis predicts that the NOV4a protein contains the domains shown in the Table 4F.

TABLE 4F
Domain Analysis of NOV4a
		Identities/
		Similarities
	NOV4a	for the Matched
Pfam Domain	Match Region	Region	Expect Value
EMP24_GP25L	13 . . . 227	80/239 (33%)	2.2e−54
		180/239 (75%)

Example 5

[0390] 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:53	1463 bp
NOV5a,	ATCCCAGTAACCCGACCACCGCTGGTCTTCACTGGACACCATGAACCACACTGTCCAAACCTTCTCTC
CG158564-02
DNA Sequence	CTATCAACAGCGGCCAGCCCCCCAACTATGAGATGCTCAAGGAGGAGCATGAGGTGGCTGTGCTGGGG
	GTGGCCTACAACCCTGCTCCCCCGACGTCCACCGTGATCCACATCCGCAACGAGACCTCCGTGCCCGA
	CCATGTTGTCTGGTCCCTGTTCAACACTCTCTTCATGAACCCCTGCTGCCTGGGCTTCATAGCATTCG
	CTTACTCCGTGAACTCTAGGCACAGGAAGATGGTTGGCGACCTGACTGGCGCCCAGGCCTATGCCTCC
	ACCGCCAAGTGCCTGAACATCTGGGCCCTGATTTTGGGCATCTTCATGACCATTCTGCTCATCATCAT
	CCCAGTGTTGATCTTCCAAGCCTATCAATAGATCAGGAGGCATCATTGAGGCCAG
	ORF Start: ATG at 41		ORF Stop: TAG at 437
	SEQ ID NO: 54	132 aa	MW at 14709.1 kD
	NOV5a,	MNHTVQTFSPINSGQPPNYEMLKEEHEVAVLGVAYNPAPPTSTVIHIRNETSVPDHVVWSLFNTLFMN
	CG158564-02
	Protein	PCCLGFIAFAYSVKSRHRKMVGDLTGAQAYASTAKCLNIWALILGIFMTILLIIIPVLIFQAYQ
	Sequence
	SEQ ID NO:55	463 bp
NOV5b,	ATCCCAGTAACCCGACCACCQCTGGTCTTCACTGGACACCATGAACCACACTGTCCAAACCTTCTCT
CG158564-01
DNA Sequence	CCTATCAACAGCGGCCAGCCCCCCAACTATGAGATGCTCAAGGAGGAGCATGAGGTGGCTGTGCTGG
	GGGTGGCCTACAACCCTGCTCCCCCGACGTCCACCGTGATCCACATCCGCAACGAGACCTCCGTGCC
	CGACCATGTTGTCTGGTCCCTGTTCAACACTCTCTTCATGAACCCCTGCTGCCTGGGCTTCATAGCA
	TTCGCTTACTCCGTGAAGTCTAGGCACAGGAAGATGGTTGGCGACCTGACTGGCGCCCAGGCCTATG
	CCTCCACCGCCAAGTGCCTGAACATCTGGGCCCTGATTTTGGGCATCTTCATGACCATTCTGCTCAT
	CATCATCCCAGTGTTGATCTTCCAAGCCTATCAATAGATCAGGAGGCATCATTGAGGCCAG
	ORF Start ATG at 41		ORF Stop: TAG at 437
	SEQ ID NO:56	1132 aa	MW at 14709.1 kD
NOV5b,	MNHTVQTFSPINSGQPPNYEMLKEEHEVAVLGVAYNPAPPTSTVIHIRNETSVPDHVVWSLFNTLFM
CG158564-01
Protein	NPCCLGFIAFAYSVKSRHRKMVGDLTGAQAYASTAKCLNIWALILGIFMTILLIIIPVLIFQAYQ
Sequence

[0391] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 5B.

TABLE 5B
Comparison of NOV5a against NOV5b.
	NOV5a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV5b	1 . . . 132	132/132 (100%)
	1 . . . 132	132/132 (100%)

[0392] Further analysis of the NOV5a protein yielded the following properties shown in Table 5C.

TABLE 5C
Protein Sequence Properties NOV5a
SignalP	No Known Signal Sequence Predicted
analysis:
PSORT II	PSG: a new signal peptide prediction method
analysis:	N-region: length 0; pos.chg 0; neg.chg 0
	H-region: length 19; peak value 4.24
	PSG score: −0.16
	GvH: von Heijne's method for signal seq. recognition
	GvH score (threshold: −2.1): −9.01
	possible cleavage site: between 13 and 14
	>>> Seems to have no N-terminal signal peptide
	ALOM: Klein et al's method for TM region allocation
	Init position for calculation: 1
	Tentative number of TMS(s) for the threshold 0.5: 2
	Number of TMS(s) for threshold 0.5: 1
	INTEGRAL Likelihood = −13.80 Transmembrane 111-127
	PERIPHERAL Likelihood = 6.79 (at 29)
	ALOM score: −13.80 (number of TMSs: 1)
	MTOP: Prediction of membrane topology (Hartmann et al.)
	Center position for calculation: 118
	Charge difference: 0.0 C(0.0)-N(0.0)
	N >= C: N-terminal side will be inside
	>>> Single TMS is located near the C-terminus
	>>> membrane topology: type Nt (cytoplasmic tail 1 to 110)
	MITDISC: discrimination of mitochondrial targeting seq
	R content:	0	Hyd Moment (75):	4.44
	Hyd Moment (95):	8.97	G content:	1
	D/E content:	1	S/T content:	4
	Score:	−4.16
	Gavel: prediction of cleavage sites for mitochondrial preseq
	cleavage site motif not found
	NUCDISC: discrimination of nuclear localization signals
	pat4: RHRK (3) at 84
	pat7: none
	bipartite: none
	content of basic residues: 5.3%
	NLS Score: −0.29
	KDEL: ER retention motif in the C-terminus: none
	ER Membrane Retention Signals: none
	SKL: peroxisomal targeting signal in the C-terminus: none
	PTS2: 2nd peroxisomal targeting signal: none
	VAC: possible vacuolar targeting motif: none
	RNA-binding motif: none
	Actinin-type actin-binding motif:
	type 1: none
	type 2: none
	NMYR: N-myristoylation pattern: none
	Prenylation motif: none
	memYQRL: transport motif from cell surface to Golgi: none
	Tyrosines in the tail: too long tail
	Dileucine motif in the tail: none
	checking 63 PROSITE DNA binding motifs:
	Leucine zipper pattern (PS00029): *** found ***
	LNIWALILGIFMTILLIIIPVL at 105
	none
	checking 71 PROSITE ribosomal protein motifs: none
	checking 33 PROSITE prokaryotic DNA binding motifs: none
	NNCN: Reinhardt's method for Cytoplasmic/Nuclear
	discrimination
	Prediction: cytoplasmic
	Reliability: 94.1
	COIL: Lupas's algorithm to detect coiled-coil regions
	total: 0 residues
Final Results (k = 9/23):
26.1%: nuclear
21.7%: cytoplasmic
17.4%: Golgi
8.7%: mitochondrial
8.7%: vesicles of secretory system
8.7%: endoplasmic reticulum
4.3%: extracellular, including cell wall
4.3%: peroxisomal
>> prediction for CG158564-02 is nuc (k = 23)

[0393] 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
		NOV5a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
ABP43105	Human ovarian antigen	1 . . . 131	122/132 (92%)	3e−67
	HVCBB19, SEQ ID NO: 4237 -	11 . . . 142	127/132 (95%)
	Homo sapiens, 143 aa.
	[WO200200677-A1,
	03-JAN-2002]
AAE13797	Human lung tumor-specific	1 . . . 131	122/132 (92%)	3e−67
	protein SALT-T8 - Homo	1 . . . 132	127/132 (95%)
	sapiens, 133 aa.
	[WO200172295-A2,
	04-OCT-2001]
AAB44456	antigen encoded by cDNA	1 . . . 132	127/132 (95%)	3e−67
	#71 - Homo sapiens, 133 aa.
	[WO200060077-A2,
	12-OCT-2000]
AAY29544	Human lung tumor protein	1 . . . 131	122/132 (92%)	3e−67
	SALT-T8 predicted amino	1 . . . 132	127/132 (95%)
	acid sequence - Homo
	sapiens, 133 aa.
	[WO9938973-A2,
	05-AUG-1999]
AAY93594	Protein encoded by I-8U gene	1 . . . 131	121/132 (91%)	3e−66
	from interferon-inducible	1 . . . 132	127/132 (95%)
	gene family - Homo sapiens,
	133 aa. [WO200035473-A2,
	22-JUN-2000]

[0394] 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
		NOV5a	Identities/
Protein		Residues/	Similarities for
Accession	Protein/	Match	the Matched	Expect
Number	Organism/Length	Residues	Portion	Value
Q01628	Interferon-induced	1 . . . 131	122/132 (92%)	9e−67
	transmembrane protein	1 . . . 132	127/132 (95%)
	3 (Interferon-inducible
	protein 1-8U) - Homo
	sapiens (Human),
	133 aa.
S17182	interferon-induced	1 . . . 131	121/132 (91%)	8e−66
	protein 1-8U -	1 . . . 132	127/132 (95%)
	human, 133 aa.
Q01629	Interferon-induced	1 . . . 130	116/130 (89%)	8e−64
	transmembrane	1 . . . 130	123/130 (94%)
	protein 2 (Interferon-
	inducible protein
	1-8D) - Homo sapiens
	(Human), 132 aa.
Q95MQ3	Interferon-induced	1 . . . 123	83/124 (66%)	4e−43
	protein 1-8U - Bos	1 . . . 124	104/124 (82%)
	taurus
	(Bovine), 146 aa.
JC1241	beta-interferon-	1 . . . 127	85/128 (66%)	1e−42
	induced protein - rat,	1 . . . 128	101/128 (78%)
	137 aa.

[0395] PFam analysis predicts that the NOV5a protein contains the domains shown in the Table 5F.

TABLE 5F
Domain Analysis of NOV5a
		Identities/
		Similarities
	NOV5a	for the Matched
Pfam Domain	Match Region	Region	Expect Value
No Significant Matches Found

Example 6

[0396] The NOV6 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 6A.

TABLE 6A
NOV6 Sequence Analysis
	SEQ ID NO:57	3488 bp
NOV6a,	ATCTGTGGGGATTCTCACAACTTCCATTTCTGGTGAACAGCTGAGGTCAGAGAGGAGTTGGTCCAGGC
CG159093-01
DNA Sequence	GCAATGTTCAGCGTATTTGAGGAAATCACAAGAATTGTAGTTAAGCAGATGGATGCTGGAGGGGATAT
	GATTGCCGTTAGAAGCCTTGTTGATCCTGATAGATTCCGCTGCTTCCATCTGGTGGGGGAGAAGACAA
	CTTTCTTTGGATGCCGGCACTACACAACAGGCCTCACCCTGATGGACATTCTGGACACAGATGGGGAC
	AAGTGGTTAGATGAACTGGATTCTGGGCTCCAAGGTCAAAAGGCTGAGTTTCAAATTCTGGATAATGT
	AGACTCAACGGGAGAGTTGATAGTGAGATTACCCAAAGAAATAACAATTTCAGGCAGTTTCCAGGGCT
	TCCACCATCAGAAAATCAAGATATCGGAGAACCGGATATCCCAGCAGTATCTGGCTACCCTTGAAAAC
	AGGAAGCTGAAGAGGGAACTACCCTTTTCATTCCGATCAATTAATACGAGAGAAAACCTGTATCTGGT
	GACAGAAACTCTGGAGACCGTAAAGGAGGAAACCCTGAAAAGCGACCGGCAATATAAATTTTGCAGCC
	AGATCTCTCAGGGCCATCTCAGCTATAAACACAAGGGCCAAAGCGAAGTGACCATCCCCCCAAATCGG
	GTCCTGAGCTATCGAGTAAAGCAGCTTGTCTTCCCCAACAAGGAGACGATGGGAAAGTCTTTGGGTTC
	GGAGGATTCCAGAAACATGAACGAGAAGTTGGAGGACATGGAGAGTGTCCTCAAGGACCTGACAGAGG
	AGAAGAGAAAAGATGTGCTAAACTCCCTCGCTAAGTGCCTCGGCAAGGAGGATATTCGCCAGGATCTA
	GAGCAAAGAGTATCTGAQGTCCTGATTTCCAGGGAGCTACACATGGAGGACTCAGACAAGCCTCTCCT
	AAGCAGCCTTTTTAATCCTGCTGGGGTCTTGGTAGAAQCGCGTGCAAAAGCCATTCTGGACTTCCTGG
	ATGCCCTGCTACAGCTGTCTGAAGAQCAGCAGTTTGTGGCTGACOCCCTGGAGAAGGGGACCCTTCCT
	CTGTTGAAGGACCAGGTGAAATCTGTCATGGAGCACAACTCGGATGAGCTGGCCAGCAGTCCTCCTGA
	CATGGACTATGACCCTGAGGCACGAATTCTCTGTGCGCTCTATGTTGTTGTCTCTATCCTGCTGGAGC
	TGGCTGAGGGGCCTACCTCTGTCTCTTCCTAACTACAAAAGCCCTTTCTCCCCACAAQCCTCTGGGTT
	TTCCCTTTACCAGTCTGTCCTCACTGCCATCGCCACTACCATCCTGTCACCAGTCGGACCTCTTTAAA
	ACAAGCAGCCAACCATTCTTTGATGTATCCCATTCGCTCCATGTTAACATCCAAAACCACCCTCGATT
	TCATACATGGACTTCTGATTAAAAGTGGCAGGTTGTGCATGTTAAAAAAAAAAAAAA
	ORF Start: ATG at 72		ORF Stop: TAA at 1254
	SEQ ID NO:58	394 aa	MW at 45002.8 kD
NOV6a,	MFSVFEEITRIVVKEMDAGGDMIAVRSLVDADRFRCFHLVGEKRTFFGCRHYTTGLTLMDILDTDGDK
CG159093-01
Protein	WLDELDSGLQGQKAEFQILDNVDSTGELIVRLPKEITISGSFQGFHHQKIKISENRISQQYLATLENR
Sequence
	KLKRELPFSFRSINTRENLYLVTETLETVKEETLKSDRQYKFWSQISQGHLSYKHKGQREVTIPPNRV
	LSYRVKQLVFPNKETMGKSLGSEDSRNMKEKLEDMESVLKDLTEEKRKDVLNSLAKCLGKEDIRQDLE
	QRVSEVLISRELHMEDSDKPLLSSLFNAAGVLVEARAKAILDFLDALLELSEEQQFVAEALEKGTLPL
	LKDQVKSVMEQNWDELASSPPDMDYDPEARILCALYVVVSILLELAEGPTSVSS
	SEQ ID NO:59	1434 bp
NOV6b,	ATCTGTGGGGATTCTCACAACTTCCATTTCTGGTGAACAGCTGAGGTCAGAGAGGAGTTGGTCCAGG
CG159093-02
DNA Sequence	CCCAATGTTCAGCGTATTTGAGGAAATCACAAGAATTGTAGTTAAGGAGATGGATGCTGGAGGGGAT
	ATGATTGCCGTTAGAAGCCTTGTTGATGCTGATAGATTCCGCTGCTTCCATCTGGTGGGGGAGAACA
	GAACTTTCTTTGGATGCCGGCACTACACAACAGGCCTCACCCTGATGGACATTCTGGACACAGATGG
	GGACAAGTGGTTAGATGAACTGGATTCTGGGCTCCAAGGTCAAAAGGCTCAGTTTCAAATTCTGQAT
	AATGTAGACTCAACGGCAGAGTTQATAGTGAGATTACCCAAAGAAATAACAATTTCAGGCAGTTTCC
	AGGGCTTCCACCATCAGAAAATCAAGATATCGGAGAACCGGATATCCCAGCACTATCTCGCTACCCT
	TGAAAACAGGAACCTGAAGACGGAACTACCCTTTTCATTCCGATCAATTAATACGAGAGAAAACCTG
	TATCTGGTGACAGAAACTCTGGAGACGGTAAAGGAGGAAACCCTGAAAAGCGACCGGCAATATAAAT
	TTTCGAGCCACATCTCTCAGGGCCATCTCAGCTATAAACACAAGAAGAAGGATGGTGCTTCATCCTG
	TTTAGGAAAGTCTTTGGGTTCGGAGGATTCCAGAAACATGAAGGAGAAGTTGGAGCACATGGAGAGT
	GTCCTCAAGGACCTGACAGAGGAGAAGAGAAAAGATGTGCTAAACTCCCTCGCTAAGTGCCTCGGCA
	AGGAGGATATTCGGCAGQATCTAGAGCAAAGAGTATCTGAGGTCCTGATTTCCAGGCAGCTACACAT
	GGAGGACTCAGACAAGCCTCTCCTAAGCAGCCTTTTTAATGCTGCTGGGGTCTTGGTAGAAGCGCGT
	GCAAAAGCCATTCTGGACTTCCTGGATGCCCTGCTAGAGCTGTCTGAAGAGCAGCAGTTTGTGGCTG
	AGGCCCTGGAGAAGGGGACCCTTCCTCTGTTGAAGGACCAGGTGAAATCTGTCATGGAGCAGAACTG
	GGATGAGCTGCCCAQCAGTCCTCCTGACATGGACTATGACCCTGAGGCACGAATTCTCTGTGCGCTG
	TATGTTGTTGTCTCTATCCT~CTGGAGCTGGCTGAGGGGCCTACCTCTGTCTCTTCCTAACTACAAA
	AGCCCTTTCTCCCCACAAGCCTCTGGGTTTTCCCTTTACCAGTCTGTCCTCACTGCCATCGCCACTA
	CCATCCTGTCACCAGTGGGACCTCTTTAAAACAAGCAGCCAACCATTCTTTGATGTATCCCATTCGC
	TCCATGTTAACATCCAAAACCAGCCTGGATTTCATACATGGACTTCTCATTAAAAGTGGCAGGTTGT
	GCATGTTAAAAAAAAAAAAAAAAAAAA
	ORF Start: ATG at 72		ORF Stop: TAA at 1197
	SEQ ID NO:60	375 aa	MW at 42609.9 kD
NOV6b,	MFSVFEEITRIVVKEMDAQGDMIAVRSLVDADRFRCFHLVGEKRTPFGCRHYTTGLTLMDILDTDGD
CG159093-02
Protein	KWLDELDSGLQGQKAEFQILDNVDSTGELIVRLPKEITISGSFQGFHHQKIKISENRISQQYLATLE
Sequence
	NRKLKRELPFSFRSINTRENLYLVTETLETVKEETLKSDRQYKFWSQISQGHLSYKHKKKDQASSCL
	GKSLGSEDSRNMKEKLEDMESVLKDLTEEKRKDVLNSLAKCLGKEDIRQDLEQRVSEVLISRELHME
	DSDKPLLSSLFNAAGVLVEARAKAILDFLDALLELSEEQQFVAEALEKGTLPLLKDQVKSVMEQNWD
	ELASSPPDMDYDPFARILCALYVVVSILLELAEGPTSVSS
	SEQ ID NO:61	1401 bp
NOV6c,	ATCTGTGCGGATTCTCACAACTTCCATTTCTCGTGAACAGCTGAGGTCAGAGAGGAGTTGGTCCAGGC
CG159093-03
DNA Sequence	GCAATGTTCAGCGTATTTGAGGAAATCACAAGAATTGTAGTTAAGGAGATGGATGCTGGAGGGGATAT
	GATTGCCGTTAGAAGCCTTGTTGATGCTCATAGATTCCGCTGCTTCCATCTGGTGGGGGAGAAGAGAA
	CTTTCTTTGGATQCCCGCACTACACAACAGGCCTCACCCTGATGGACATTCTGGACACAGATGGGGAC
	AAGTGGTTAGATGAACTCGATTCTGGGCTCCAAGGTCAAAAGGCTGAGTTTCAAATTCTGGATAATGT
	AGACTCAACGGGAGAGTTGATAGTGAGATTACCCAAAGAAAGAACAATTTCAGGCAGTTTCCAGGGCT
	TCCACCATCAGAAAATCAAGATATCGGAGAACCGGATATCCCAGCAGTATCTGGCTACCCTTGAAAAC
	AGGAAGCTGAAGAGGGAACTACCCTTTTCATTCCGATCAATTAATACGAGAGAAAACCTGTATCTGGT
	GACAGAAACTCTGGAGACGGTAAAGGAGGAAACCCTGAAAAGCGACCCGCAATATAAATTTTGGAGCC
	AGATCTCTCAGGGCCATCTCAGCTATAAACACAAGAAGTCTTTGGGTTCGGAGGATTCCAGAAACATG
	AAGGAGAAGTTGGAGGACATGGAGAGTGTCCTCAACGACCTGACAGAGGAGAAGAGAAAAGATGTGCT
	AAACTCCCTCGCTAAGTGCCTCGGCAAGGAGGATATTCGGCAGGATCTAGAGCAAAGAGTATCTGAGG
	TCCTGATTTCCAGGGAGCTACACATGGAGGACTCAGACAAGCCTCTCCTAAGCAGCCTTTTTAATGCT
	GCTCGGGTCTTGGTAGAAGCGCGTGCAAAAGCCATTCTGGACTTCCTGGATGCCCTGCTA~ACCTGTC
	TGAAGAGCAGCAGTTTGTGGCTGAGGCCCTGGAGAAGCGGACCCTTCCTCTGTTGAAGGACCAGGTGA
	AATCTGTCATGGAGCAGAACTGGGATGAGCTGGCCAGCAGTCCTCCTGACATGGACTATGACCCTGAG
	GCACGAATTCTCTGTGCGCTGTATGTTGTTGTCTCTATCCTGCTGGAGCTGGCTGACGGGCCTACCTC
	TGTCTCTTCCTAACTACAAAAGCCCTTTCTCCCCACAAGCCTCTCGGTTTTCCCTTTACCAGTCTGTC
	CTCACTGCCATCGCCACTACCATCCTGTCACCAGTGGGACCTCTTTAAAACAAGCAGCCAACCATTCT
	TTGATGTATCCCATTCGCTCCATGTTAACATCCAAAACCAGCCTGGATTTCATACATGGACTTCTGAT
	TAAAGTGGCACGTTGTGCATGTTAAAAAAAAAAAAAAAAAA
	ORF Start: ATG at 72		ORF Stop: TAA at 1167
	SEQ ID NO:62	365 aa	MW at 41662.9 kD
NOV6c,	MFSVFEEITRIVVKEMDAGGDMIAVRSLVDADRFRCFHLVGEKRTFFGCRHYTTGLTLMDILDTDGDK
CG159093-03
Protein	WLDELDSGLQCQKAEFQILDNVDSTCELIVRLPKEITISCSFQGFHHQKIKISENRISQQYLATLENR
Sequence
	KLKRELPFSFRSINTRENLYLVTETLETVKEETLKSDRQYKFWSQISQGHLSYKHKKSLGSEDSRNMK
	EKLEDMESVLKDLTEEKRKDVLNSLAKCLGKEDIRQDLEQRVSEVLISRELHMEDSDKPLLSSLFNAA
	GVLVEARAKAILDFLDALLELSEEQQFVAEALEKGTLPLLKDQVKSVMEQNWDELASSPPDMDYDPEA
	RILCALYVVVSILLELAEGPTSVSS

[0397] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 6B.

TABLE 6B
Comparison of NOV6a against NOV6b and NOV6c.
	NOV6a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV6b	1 . . . 394	366/394 (92%)
	1 . . . 375	369/394 (92%)
NOV6c	1 . . . 394	365/394 (92%)
	1 . . . 365	365/394 (92%)

[0398] Further analysis of the NOV6a protein yielded the following properties shown in Table 6C.

TABLE 6C
Protein Sequence Properties NOV6a
SignalP	No Known Signal Sequence Predicted
analysis:
PSORT II	PSG: a new signal peptide prediction method
analysis:	N-region: length 10; pos.chg 1; neg.chg 2
	H-region: length 3; peak value 0.00
	PSG score: −4.40
	GvH: von Heijne's method for signal seq. recognition
	GvH score (threshold: −2.1): −9.00
	possible cleavage site: between 31 and 32
	>>> Seems to have no N-terminal signal peptide
	ALOM: Klein et al's method for TM region allocation
	Init position for calculation: 1
	Tentative number of TMS(s) for the threshold 0.5: 1
	Number of TMS(s) for threshold 0.5: 1
	INTEGRAL Likelihood = −5.68 Transmembrane 371-387
	PERIPHERAL Likelihood = 3.50 (at 297)
	ALOM score: −5.68 (number of TMSs: 1)
	MTOP: Prediction of membrane topology (Hartmann et al.)
	Center position for calculation: 378
	Charge difference: 1.0 C(−2.0)-N(−3.0)
	C > N: C-terminal side will be inside
	>>> Single TMS is located near the C-terminus
	>>> membrane topology: type Nt (cytoplasmic tail 1 to 370)
	MITDISC: discrimination of mitochondrial targeting seq
	R content:	0	Hyd Moment (75):	6.38
	Hyd Moment(95):	9.01	G content:	0
	D/E content:	2	S/T content:	1
	Score:	−6.37
	Gavel: prediction of cleavage sites for mitochondrial preseq
	cleavage site motif not found
	NUCDISC: discrimination of nuclear localization signals
	pat4: none
	pat7: none
	bipartite: none
	content of basic residues: 13.2%
	NLS Score: −0.47
	KDEL: ER retention motif in the C-terminus: none
	ER Membrane Retention Signals: none
	SKL: peroxisomal targeting signal in the C-terminus: none
	PTS2: 2nd peroxisomal targeting signal: none
	VAC: possible vacuolar targeting motif: none
	RNA-binding motif: none
	Actinin-type actin-binding motif:
	type 1: none
	type 2: none
	NMYR: N-myristoylation pattern: none
	Prenylation motif: none
	memYQRL: transport motif from cell surface to Golgi: none
	Tyrosines in the tail: too long tail
	Dileucine motif in the tail: found
	LL at 293
	LL at 319
	LL at 340
	checking 63 PROSITE DNA binding motifs: none
	checking 71 PROSITE ribosomal protein motifs: none
	checking 33 PROSITE prokaryotic DNA binding motifs: none
	NNCN: Reinhardt's method for Cytoplasmic/Nuclear
	discrimination
	Prediction: cytoplasmic
	Reliability: 76.7
	COIL: Lupas's algorithm to detect coiled-coil regions
	221 K	0.91
	222 S	0.91
	223 L	0.95
	224 G	0.99
	225 S	0.99
	226 E	0.99
	227 D	0.99
	228 S	0.99
	229 R	0.99
	230 N	0.99
	231 M	0.99
	232 K	0.99
	233 E	0.99
	234 K	0.99
	235 L	0.99
	236 E	0.99
	237 D	0.99
	238 M	0.99
	239 E	0.99
	240 S	0.99
	241 V	0.99
	242 L	0.99
	243 K	0.99
	244 D	0.99
	245 L	0.99
	246 T	0.99
	247 E	0.99
	248 E	0.99
	249 K	0.99
	250 R	0.99
	251 K	0.99
	252 D	0.99
	253 V	0.98
	254 L	0.92
	255 N	0.92
	256 S	0.92
	257 L	0.75
	258 A	0.68
	total: 38 residues
	Final Results (k = 9/23):
	26.1%: cytoplasmic
	26.1%: nuclear
	13.0%: Golgi
	13.0%: endoplasmic reticulum
	8.7%: mitochondrial
	8.7%: vesicles of secretory system
	4.3%: peroxisomal
	>> prediction for CG159093-01 is cyt (k = 23)

[0399] 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 6D.

TABLE 6D
Geneseq Results for NOV6a
		NOV6a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent#, Date]	Residues	Region	Value
ABB97522	Novel human protein SEQ ID	1 . . . 394	392/403 (97%)	0.0
	NO: 790 - Homo sapiens, 403	1 . . . 403	392/403 (97%)
	aa. [WO200222660-A2,
	21-MAR-2002]
ABB90047	Human polypeptide SEQ ID	205 . . . 394	176/195 (90%)	6e−91
	NO: 2423 - Homo sapiens,	3 . . . 197	181/195 (92%)
	197 aa. [WO200190304-A2,
	29-NOV-2001]
AAO17132	Human cancer cell growth	232 . . . 394	161/163 (98%)	9e−84
	inhibitor related protein SEQ	1 . . . 163	161/163 (98%)
	ID NO: 8 - Unidentified, 163
	aa. [CN1324819-A,
	05-DEC-2001]
AAB93904	Human protein sequence SEQ	1 . . . 389	120/497 (24%)	3e−14
	ID NO: 13862 - Homo	1 . . . 483	204/497 (40%)
	sapiens, 484 aa.
	[EP1074617-A2,
	07-FEB-2001]
ABB90142	NO 2518 - Homo sapiens,	1 . . . 427	187/441 (42%)	1e−13
	478 aa. [WO200190304-A2,
	29-NOV-2001]

[0400] 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 6E.

TABLE 6E
Public BLASTP Results for NOV6a
		NOV6a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9NX71	Hypothetical protein	1 . . . 394	394/403 (97%)	0.0
	FLJ20402 - Homo sapiens	1 . . . 403	394/403 (97%)
	(Human), 403 aa.
Q9P163	PRO2521 - Homo sapiens	1 . . . 394	390/394 (98%)	0.0
	(Human), 394 aa.	1 . . . 394	390/394 (98%)
Q8TAX9	Similar to hypothetical	1 . . . 394	394/411 (95%)	0.0
	protein PRO2521 - Homo	1 . . . 411	394/411 (95%)
	sapiens (Human), 411 aa.
CAD35038	Sequence 346 from Patent	1 . . . 394	392/403 (97%)	0.0
	WO0222660 - Homo sapiens	1 . . . 403	392/403 (97%)
	(Human), 403 aa.
Q8WY76	PP4052 - Homo sapiens	232 . . . 394	161/163 (98%)	3e−83
	(Human), 163 aa.	1 . . . 163	161/163 (98%)

[0401] PFam analysis predicts that the NOV6a protein contains the domains shown in the Table 6F.

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

Example 7

[0402] 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:63	1607 bp
NOV7a,	CCCGGAATGCGCCAGCTGGGAGGGTCTCTCCGCCCCCCGCGCGCGGCCCACGGGGCCGAQCCTCTCCC
CG159390-01
DNA Sequence	CAGTGCGCTGGGCCCCTGCGCTGGGGGTGACCGGGACCTCGGTCGCGGAACCCCCGGATGCGAGCCCA
	GGCGCGCCAGCGTCCCCATCCACGAGCAGGTCGACCCCCCGCGAGAGGCCCTCAGCAGTGGCCCCTTC
	CCTCCACGGGCTGCCCCGCACCTCAGTCCCACCCCCTCCGCCGATGAGGCCATGAGGCACCGAACGGA
	CCTGGGCCAGAACCTCCTGCTCTTCCTGTCGGCCCTGCTGAACTGTGGTTTGGGGGTCAGTGCTCAGC
	GTCCGGGCGAGTGGACCCCGTGCGTGTCCTGGACCCGCTGCTCCAGCTCCTGCGGGCGTGGCGTCTCT
	GTGCGCAGCCGGCGCTGCCTCCGGCTTCCTGCGGAAGAACCGTGCTGGGGAGACTCCCATGAGTACCG
	CCTCTGCCAGTTCCCAGACTCCCCCCCAGGGGCTGTOCCCTTCCGAGACCTACAGTGTGCCCTGTACA
	ATGGCCGCCCTGTCCTGGGCACCCAGAAGACCTACCAGTGGGTGCCCTTCCATGGCGCGCCCAACCAG
	TGCGACCTCAACTGCCTGGCTGACGGGCACGCCTTCTACCACAGCTTCGGCCGCGTCCTGGACGGCAC
	CGCCTGCAGCCCGGGTGCCCAGGGGGTCTGCGTGGCTGGCCGCTGCCTTAGCGCCGGCTGTGATGGGT
	TGTTGGGCTCGGGTGCCCTCGAGGACCGCTGTGGCCGCTGCGGAGGCGCCAACGACTCGTGCCTTTTC
	GTGCAGCGCGTGTTTCGTGACGCCCGTGCCTTCGCTGGGTACTCGAACGTGACCCTGATCCCCGAGGG
	CGCCAGACACATCCGCGTGGAACACAGGAGCCGCAACCACCTGGGTATCCTAQGATCACTGATGGGGG
	GCCATGGGCGCTACGTGCTTAATCGGCACTGGGTCGTCAGCCCACCACGGACCTACGACGCGGCCGGC
	ACGCATGTCGTCTACACCCGAGACACACGGCCCCAGGAGACATTGCAAGCAGCCGGGCCCACCTCCCA
	TGACCTGCTCCTACAGGTCCTCCTGCAGGAGCCCAACCCTGGCATCGAGTTTGAGTTCTGGCTCCCTC
	GGGAGCGCTACAGCCCCTTCCAGGCTCCTGTGCAGGCCCTGGGCTGGCCCCTGAGGCAGCCTCAGCCC
	CGCGGCGTGGAGCCTCAGCCCCCCGCAGCCCCTGCTGTCACCCCTGCACAGACCCCAACGCTGGCCCC
	AGTGTTCCAGGCCCGAGTGCTGGGCCACCACCACCAGGCCCAGGAGACCCGCTATGAGGTGCGCATCC
	AGCTCGTCTACAAGAACCGCTCGCCACTGCGCGCACGCGAGTACGTGTGGGCGCCAGGCCACTGCCCC
	TGCCCGATGCTGGCACCCCACCGGGACTACCTGATGGCTGTCCAGCGTCTTGTCAGCCCCGACGGCAC
	ACAGGACCAGCTGCTGCTGCCCCACGCCGGCTACGCCCGGCCCTGGAGCCCTGCGGAGGACAGCCGCA
	TACGCCTGACTGCCCCGCGCTGTCCTGGCTGAGDDDDTGCAGG
	ORF Start: ATG at 7		ORF Stop: TGA at 1594
	SEQ ID NO:64	529 aa	MW at 57778.9 kD
NOV7a,	MRQLGGSLRPPRAAHGAEPLPSALGPCAGCDRDLGRGTPGWEPRRARVPIHEQVDPPREGLSSGPFPP
CG159390-01
Protein	RAAPELSPTPSADEAMRHRTDLGQNLLLFLWALLNCGLGVSAQGPGEWTPWVSWTRCSSSCGRGVSVR
Sequence
	SRRCLRLPGEEPCWGDSHEYRLCQLPDCPPGAVPFRDLQCALYNGRPVLGTQKTYQWVPPHQAPNQCD
	LNCLAEGHAFYHSFGRVLDGTACSPQAQGVCVAGRCLSAGCDGLLGSGALEDRCGRCGGANDSCLFVQ
	RVFRDAGAFAGYWNVTLIPEGARHIRVEHRSRNHLGILGSLMCGDGRYVLNGHWVVSPPGTYEAAGTH
	VVYTRDTGPQETLQAAGPTSHDLLLQVLLQEPNPGIEFEFWLPRERYSPFQARVQALGWPLRQPQPRG
	VEPQPPAAPAVTPAQTPTLAPVFQARVLGHHHQAQETRYEVRIQLVYKNRSPLRAREYVWAPGHCPCP
	MLAPHRDYLMAVQRLVSPDGTQDQLLLPHAGYARPWSPAEDSRIRLTARRCPG

[0403] Further analysis of the NOV7a protein yielded the following properties shown in Table 7B.

TABLE 7B
Protein Sequence Properties NOV7a
SignalP	No Known Signal Sequence Predicted
analysis:
PSORT II	PSG: a new signal peptide prediction method
analysis:	N-region: length 9; pos.chg 2; neg.chg 0
	H-region: length 2; peak value −5.17
	PSG score: −9.57
	GvH: von Heijne's method for signal seq. recognition
	GvH score (threshold: −2.1): −6.80
	possible cleavage site: between 29 and 30
	>>> Seems to have no N-terminal signal peptide
	ALOM: Klein et al's method for TM region allocation
	Init position for calculation: 1
	Tentative number of TMS(s) for the threshold 0.5: 1
	Number of TMS(s) for threshold 0.5: 1
	INTEGRAL Likelihood = −3.61 Transmembrane 94-110
	PERIPHERAL Likelihood = 3.39 (at 233)
	ALOM score: −3.61 (number of TMSs: 1)
	MTOP: Prediction of membrane topology (Hartmann et al.)
	Center position for calculation: 101
	Charge difference: 0.5 C( 0.0)-N(−0.5)
	C > N: C-terminal side will be inside
	>>> membrane topology: type lb (cytoplasmic tail 94 to 529)
	MITDISC: discrimination of mitochondrial targeting seq
	R content:	3	Hyd Moment(75):	7.96
	Hyd Moment(95):	9.93	G content:	3
	D/E content:	1	S/T content:	1
	Score:	−2.68
	Gavel: prediction of cleavage sites for mitochondrial preseq
	R-2 motif at 22 PRA|AH
	NUCDISC: discrimination of nuclear localization signals
	pat4: none
	pat7: PRRARVP (5) at 43
	bipartite: none
	content of basic residues: 10.0%
	NLS Score: −0.04
	KDEL: ER retention motif in the C-terminus: none
	ER Membrane Retention Signals:
	XXRR-like motif in the N-terminus: RQLG
	none
	SKL: peroxisomal targeting signal in the C-terminus: none
	PTS2: 2nd peroxisomal targeting signal: none
	VAC: possible vacuolar targeting motif: none
	RNA-binding motif: none
	Actinin-type actin-binding motif:
	type 1: none
	type 2: none
	NMYR: N-myristoylation pattern: none
	Prenylation motif: none
	memYQRL: transport motif from cell surface to Golgi: none
	Tyrosines in the tail: too long tail
	Dileucine motif in the tail: found
	LL at 94
	LL at 95
	LL at 101
	LL at 248
	LL at 363
	LL at 364
	checking 63 PROSITE DNA binding motifs:
	Myb DNA-binding domain repeat signature 1 (PS00037):
	*** found ***
	WSPAEDSRI at 512
	checking 71 PROSITE ribosomal protein motifs: none
	checking 33 PROSITE prokaryotic DNA binding motifs: none
	NNCN: Reinhardt's method for Cytoplasmic/Nuclear
	discrimination
	Prediction: cytoplasmic
	Reliability: 55.5
	COIL: Lupas's algorithm to detect coiled-coil regions
	total: 0 residues
Final Results (k = 9/23):
39.1%: nuclear
21.7%: mitochondrial
17.4%: cytoplasmic
8.7%: vesicles of secretory system
4.3%: vacuolar
4.3%: endoplasmic reticulum
4.3%: peroxisomal
>> prediction for CG159390-01 is nuc (k = 23)

[0404] 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
ABB80573	Human sbg98530TS protein	1 . . . 529	499/529 (94%)	0.0
	#1 - Homo sapiens, 502 aa.	1 . . . 502	499/529 (94%)
	[WO200222802-A1,
	21-MAR-2002]
AAU74754	Human protease PRTS-14	84 . . . 529	446/470 (94%)	0.0
	protein sequence - Homo sapiens,	1 . . . 470	446/470 (94%)
	470 aa.
	[WO200198468-A2,
	27-DEC-2001]
ABB80574	Human sbg98530TS protein	87 . . . 529	440/443 (99%)	0.0
	#2 - Homo sapiens, 451 aa.	9 . . . 451	440/443 (99%)
	[WO200222802-A1,
	21-MAR-2002]
AAB72282	Human ADAMTS-6 amino	114 . . . 386	113/280 (40%)	2e−52
	acid sequence - Homo	511 . . . 784	149/280 (52%)
	sapiens, 859 aa.
	[WO200111074-A2,
	15-FEB-2001]
ABG76897	Human ADAM-TS 7-like	114 . . . 420	117/315 (37%)	3e−52
	protein #2 - Homo sapiens,	624 . . . 910	162/315 (51%)
	952 aa. [WO200233087-A2,
	25-APR-2002]

[0405] In a BLAST search of public sequence datbases, the NOV7a protein was found to have homology to the proteins shown in the BLASTP data in Table 7D.

TABLE 7D
Public BLASTP Results for NOV7a
		NOV7a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9CRC7	2010109H09Rik protein -	94 . . . 279	157/186 (84%)	1e−98
	Mus musculus (Mouse), 244	27 . . . 212	167/186 (89%)
	aa.
Q8JZY8	Similar to RIKEN cDNA	94 . . . 278	156/185 (84%)	5e−98
	2010109H09 gene - Mus	27 . . . 211	166/185 (89%)
	musculus (Mouse), 215 aa.
O95428	Hypothetical protein - Homo	94 . . . 389	123/309 (39%)	6e−55
	sapiens (Human), 1235 aa.	3 . . . 304	162/309 (51%)
Q9EPX2	Papilin - Mus musculus	116 . . . 383	111/277 (40%)	2e−52
	(Mouse), 1280 aa.	30 . . . 299	147/277 (52%)
Q9UKP5	ADAMTS-6 precursor	114 . . . 386	113/280 (40%)	5e−52
	(EC 3.4.24.-) (A disintegrin and	511 . . . 784	149/280 (52%)
	metalloproteinase with
	thrombospondin motifs 6)
	(ADAM-TS 6) (ADAM-TS6) -
	Homo sapiens (Human), 860
	aa.

[0406] PFam analysis predicts that the NOV7a protein contains the domains shown in the Table 7E.

TABLE 7E
Domain Analysis of NOV7a
		Identities/
	NOV7a	Similarities for
Pfam Domain	Match Region	the Matched Region	Expect Value
tsp_1	117 . . . 164	19/54 (35%)	9.5e−08
		32/54 (59%)

Example 8

[0407] The NOV8 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 8A.

TABLE 8A
NOV8 Sequence Analysis
             SEQ ID NO: 65            1968 bp
NOV8a,       GGAATTCGCGGCAAGATGGCGGACCGTGGCGGCGTGGGTGAAGCCGCAGCTGTTGGAGCGTCTCCTGC
CG159498-01
DNA Sequence ATCTGTCCCTGGCCTAAACCCGACGCTAGGCTGGAGGGACCGACTGCGGGCCGGGCTGGCGGGGACTG
             GGGCCTCGTTGTGGTTCGTGGCGGGGCTGGGGCTGCTTTACGCCCTGAGGATCCCTTTCAGGCTGTGT
             GAGAATTTCGCAGCGGTGACTGTATTTTTAAATTCATTGACACCCAAATTCTATGTGGCACTTACAGG
             GACCTCTTCATTGATATCAGGACTAATATTTATATTTGAATGGTGGTACTTCCATAAGCATGGCACAT
             CTTTTATTGAGCAAGTATCTGTAAGCCATTTGCAACCACTGATGGGAGGAACAGAGAGCAGCATTTCA
             GAACCAGGTTCTCCTTCGAGGAACAGAGAAAATGAAACCAGCAGACAGAATTTGTCAGAATGTAAGGT
             ATGGAGAAACCCTCTAAATCTTTTCAGAGGAGCAGAATATAGGAGATACACTTGGGTGACTGGTAAAG
             AGCCACTTACATACTATGACATGAACCTGTCAGCTCAGGACCATCAGACCTTTTTCACCTGTGACACA
             GATTTTTTACGTCCTTCAGACACAGTTATGCAGAAGGCTTGGAGGGAAAGAAATCCTCCAGCTCGAAT
             CAAAGCAGCCTATCAAGCTTTAGAATTAAACAATGACTGTGCCACTGCATATGTTCTACTGGCTGAGG
             AAGAAGCAACAACTATTGTAGATGCTGAAAGGTTATTTAAACAGGCACTCAAGGCAGGAGAAACAATT
             TATAGGCAGTCACAQCAGTCCCAGCACCAAAGTCCTCAGCATGAAGCTCAACTGAGGAGAGATACCAA
             TGTACTGGTATATATTAAAAGAAGATTCGCAATGTGTGCAAGAAAATTAGGAAGAATAAGAGAAGCAG
             TAAAAATAATGAGAGATTTGATGAATGAATTTCCTCCTCTTACCATGTTGAACATCCATGAAAATCTC
             TTAGAATCACTTTTAGAATTACAQGCCTATCCAGATCTTCAGGCAGTCCTAGCAAAATATGATGATAT
             AAGCCTTCCAAAGTCAGCAGCAATCTGTTACACAGCAGCACTGTTGAAGACAAGGACTGTTTCAGAAA
             AATTCTCTCCAGAAACAGCCTCCACAAGAGGATTAAGCGCAGCAGAAATTAATCCCGTGGATGCAATT
             CATAGAGCTGTGGAATTTAATCCTCATGTTCCAAAATATTTATTAGAGATGAAAAGTTTAATTTTACC
             TCCAGAACACATTCTGAAACGGGGTGATAGTGAAGCAATTGCCTATGCTTTCTTTCATCTTCAGCACT
             GGAAACGAATAGAAGGTGCTCTTAATCTGTTACAGTGTACATCGGAACGCAGTTTTAGAATCATTCCA
             TACCCGTTAGAGAAACGACATCTATTTTACCCTTATCCCACCTGCACAGAGACCGCTGATACAGAGCT
             ATTACCTAGTTTTCATCATGTTTCTGTTTACCCAAAAAAGGAGCTTCCTTTGTTCATCCATTTCACAG
             CAGGATTTTGCTCTTCTACAGCAATGATAGCCATTCTCACTCACCAGTTTCCTGAAATCATCGGTATT
             TTTGCTAAAGCTGTAAGTATGATCTCAAGGACTTGTGTAGATTATTTGTAAAACACACAAGAAACCAT
             CTCTGATCTGCCTGTGCTAACCCAGCTGAACAATGGAAGATATTTGTTGTAAATTAAAGGAATTGATT
             TGTATATAGTTGCTGCCATAAATACATCAAACATAAATTTTTCGTGATTTGAGCTACTTCTGTTCCTT
             AAAAGTTTAAAGAATACAATATAAGATTGTAACAATATAACATTATAAAGTTTGCTCTTATAGATCAC
             TTTTGGTCATAAACAGCATTTGTTACTATCTTTGGTATTTTTAAAAATACCCTATTTTGTAAAC
             ORF Start: ATG at 16                    ORF Stop: TAA at 1681
             SEQ ID NO: 66            555aa          MW at 62572.2kD
NOV8a,       MADRGGVQEAAAVGASPASVPGLNPTLGWRERLRAGLAGTGASLWFVAGLGLLYALRIPLRLCENLAA
CG159498-01
Protein      VTVFLNSLTPKFYVALTGTSSLISGLIFIFEWWYFHKHGTSFIEQVSVSHLQPLMGGTESSISEPGSP
Sequence
             SRNRENETSRQNLSECKVWRNPLNLFRGAEYRRYTWVTGKEPLTYYDMNLSAQDHQTFFTCDTDFLRP
             SDTVMQKAWRERNPPARIKAAYQALELNNDCATAYVLLAEEEATTIVDAERLFKQALKAGETIYRQSQ
             QCQHQSPQHEAQLRRDTNVLVYIKRRLAMCARKLGRIREAVKIMRDLMNEFPPLTMLNIHENLLESLL
             ELQAYPDVQAVLAKYDDISLPKSAAICYTAALLKTRTVSEKFSPETASTRGLSAAEINAVDAIHRAVE
             FNPHVPKYLLEMKSLILPPEHILKRGDSEAIAYAFFHLQHWKRIEGALNLLQCTWEGSFRMIPYPLEK
             GHLFYPYPSCTETADRELLPSFHHVSVYPKKELPLFIHFTAGFCSSTAMIAILTHQFPEIMGIFAKAV
             SMISRTCVDYL
             SEQ ID NO: 67            1738 bp
NOV8b,       ACTATCCCACGATTCCCGACTCCCGGTTTCCTGTCCTTCTCCCCTCCCAGCTCCTGGCGCCTGCGAT
CG159498-02
             AGCGGCAAGATGGCCGACCGTGGCGGCGTGOGTGAAGCCGCAGCTGTTGCAGCGTCTCCTGCATCTG
             TCCCTGCCCTAAACCCGACGCTACGCTGGAGGGAGCGACTGCGGGCCGGGCTGGCGGGCACTGGGGC
             CTCGTTGTGGTTCCTGGCGGGGCTCGGGCTGCTTTACQCCCTGAGGATCCCTTTGAGGCTGTGTGAG
             AATTTGCCAGCGGTGACTGTATTTTTAAATTCATTGACACCCAAATTCTATGTGGCACTTACAGGGA
             CCTCTTCATTGATATCAGGACTAATATTTATATTTGAATGGTGGTACTTCCATAAGCATGGCACATC
             TTTTATTGAGCAAGTATCTGTAAGCCATTTGCAACCACTGATGGGAGGAACAGACAGCAGCATTTCA
             GAACCACGTTCTCCTTCGAGGAACAGAGAAAATGAAACCACCAGACAGAATTTGTCAGAATGTAAGG
             TATGGAGAAACCCTCTAAATCTTTTCAGAGGAGCAGAATATAGGAGATACACTTGGGTGACTGGTAA
             AGAGCCACTTACATACTATGACATGAACCTGTCAGCTCAGGACCATCAGACCTTTTTCACCTGTCAC
             ACAGATTTTTTACGTCCTTCAGACACAGTTATGCAGAAGGCTTGGAGGGAAAGAAATCCTCCAGCTC
             GAATCAAAGCAGCCTATCAAGCTTTAGAATTAAACAATGACTGTGCCACTGCATATGTTCTACTGGC
             TGAGGAACAAGCAACAACTATTGTAGATGCTGAAAGGTTATTTAAACAGGCACTCAAQGCAGGAGAA
             ACAATTTATAGGCAGTCACAGCAGTGCCAGCACCAAAGTCCTCAGCATGAAGCTCAACTGAGGAGAG
             ATACCAATGTACTGGTATATATTAAAAGAAGATTGGCAATGTGTGCAAGAAAATTAGGAAGAATAAG
             AGAAGCAGTAAAAATAATGAGAGATTTGATGAAAGAATTTCCTCCTCTTACCATGTTGAACATCCAT
             GAAAATCTCTTAGAATCACTTTTAGAATTACAGGCCTATCCAGATGTTCACGCAGTCCTAGCAAAAT
             ATGATGATATAAGCCTTCCAAAGTCAGCAGCAATCTGTTACACAGCAGCACTGTTGAAGACAAGGAC
             TGTTTCAGAAAAATTCTCTCCAGAAACAGCCTCCAGAAGAGGATTAACCACAGCAGAAATTAATGCC
             GTGGAAGCAATTCATACAGCTGTGGAATTTAATCCTCATGTTCCAAAATATTTATTAGACATGAAAA
             GTTTAATTTTACCTCCAGAACACATTCTGAAACGGCGTGATAGTGAAGCAATTGCCTATGCTTTCTT
             TCATCTTCAGCACTGGAAACCAATAGAAGQTGCTCTTAATCTGTTACAGTGTACATGGGAAGGCACC
             TTTCATCATGTTTCTGTTTACCCAAAAAAGGAGCTTCCTTTGTTCATCCATTTCACAGCAGGATTTT
             GCTCTTCTACAGCAATGATAGCCATTCTCACTCACCAGTTTCCTGAAATCATGGGTATTTTTGCTAA
             AGCTGTGCTGGGACTCTGGTGCCCCCAACCCTGGGCATCCTCAGGCTTTGAGCAGAATACACAGGAT
             TTGAAGTCAQAAGACCTAGGTTTGAGTTCTGGCTGAGCCACGCACTGTTCATGTGACCTTGGA
             ORF Start: ATG at 77                    ORF Stop: TGA at 1709
             SEQ ID NO: 68            544 aa         MW at 61110.4kD
NOV8b,       MADRGGVGEAAAVGASPASVPGLNPTLGWRERLRAGLAGTGASLWFVAGLGLLYALRIPLRLCENLA
CG159498-02
Protein      AVTVFLNSLTPKFYVALTGTSSLISGLIFIFEWWYPHKHGTSFIEQVSVSHLQPLMGGTESSISEPG
Sequence
             SPSRNRENETSRQNLSECKVWRNPLNLPRGAEYRRYTWVTGKEPLTYYDMNLSAQDHQTFFTCDTDF
             LRPSDTVMQKAWRERNPPARIKAAYQALELNNDCATAYVLLAEEEATTIVDAERLFKQALKAGETIY
             RQSQQCQHQSPQMEAQLRRDTNVLVYIKRRLAMCARKLGRTREAVKIMRDLMKEFPPLTMLNIHENL
             LESLLELQAYPDVQAVLAKYDDISLPKSAAICYTAALLKTRTVSEKFSPETASRRGLSTAEINAVEA
             IHRAVEFNPHVPKYLLEMKSLILPPEHILKRGDSEAIAYAFFHLQHWKRIEGALNLLQCTWEGTPHH
             VSVYPKKELPLFIHFTAGFCSSTAMIAILTHQFPEIMGIPAKAVLGLWCPQPWASSGFEENTQDLKS
             EDLGLSSG

[0408] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 8B.

TABLE 8B
Comparison of NOV8a against NOV8b.
	NOV8a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV8b	1 . . . 544	508/544 (93%)
	1 . . . 513	510/544 (93%)

[0409] Further analysis of the NOV8a protein yielded the following properties shown in Table 8C.

TABLE 8C
Protein Sequence Properties NOV8a
SignalP	Cleavage site between residues 64 and 65
analysis:
PSORT II	PSG: a new signal peptide prediction method
analysis:	N-region: length 9; pos.chg 1; neg.chg 2
	H-region: length 20; peak value 0.00
	PSG score: −4.40
	GvH: von Heijne's method for signal seq. recognition
	GvH score (threshold: −2.1): −2.39
	possible cleavage site: between 55 and 56
	>>> Seems to have no N-terminal signal peptide
	ALOM: Klein et al's method for TM region allocation
	Init position for calculation: 1
	Tentative number of TMS(s) for the threshold 0.5: 3
	Number of TMS(s) for threshold 0.5: 1
	INTEGRAL Likelihood = −2.66 Transmembrane 82-98
	PERIPHERAL Likelihood = 1.80 (at 536)
	ALOM score: −2.66 (number of TMSs: 1)
	MTOP: Prediction of membrane topology (Hartmann et al.)
	Center position for calculation: 89
	Charge difference: −1.0 C( 0.0)-N(1.0)
	N >= C: N-terminal side will be inside
	>>> membrane topology: type 2 (cytoplasmic tail 1 to 82)
	MITDISC: discrimination of mitochondrial targeting seq
	R content:	1	Hyd Moment(75):	11.73
	Hyd Moment(95):	8.52	G content:	3
	D/E content:	2	S/T content:	0
	Score:	−6.50
	Gavel: prediction of cleavage sites for mitochondrial preseq
	cleavage site motif not found
	NUCDISC: discrimination of nuclear localization signals
	pat4: none
	pat7: none
	bipartite: none
	content of basic residues: 10.5%
	NLS Score: −0.47
	KDEL: ER retention motif in the C-terminus: none
	ER Membrane Retention Signals:
	XXRR-like motif in the N-terminus: ADRG
	none
	SKL: peroxisomal targeting signal in the C-terminus: none
	PTS2: 2nd peroxisomal targeting signal: none
	VAC: possible vacuolar targeting motif: none
	RNA-binding motif: none
	Actinin-type actin-binding motif:
	type 1: none
	type 2: none
	NMYR: N-myristoylation pattern: none
	Prenylation motif: none
	memYQRL: transport motif from cell surface to Golgi: none
	Tyrosines in the tail: too long tail
	Dileucine motif in the tail: found
	LL at 52
	checking 63 PROSITE DNA binding motifs:
	Leucine zipper pattern (PS00029):
	*** found ***
	LRRDTNVLVYIKRRLAMCARKL at 285
	none
	checking 71 PROSITE ribosomal protein motifs: none
	checking 33 PROSITE prokaryotic DNA binding motifs: none
	NNCN: Reinhardt's method for Cytoplasmic/Nuclear
	discrimination
	Prediction: cytoplasmic
	Reliability: 76.7
	COIL: Lupas's algorithm to detect coiled-coil regions
	total: 0 residues
Final Results (k = 9/23):
39.1%: mitochondrial
30.4%: cytoplasmic
8.7%: endoplasmic reticulum
4.3%: Golgi
4.3%: vacuolar
4.3%: extracellular, including cell wall
4.3%: nuclear
4.3%: vesicles of secretory system
>> prediction for CG159498-01 is mit (k = 23)

[0410] 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 8D.

TABLE 8D
Geneseq Results for NOV8a
		NOV8a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAM79736	Human protein SEQ ID NO	1 . . . 471	371/476 (77%)	0.0
	3382 - Homo sapiens, 486 aa.	6 . . . 476	388/476 (80%)
	[WO200157190-A2,
	09-AUG-2001]
ABB71248	Drosophila melanogaster	70 . . . 544	334/503 (66%)	0.0
	polypeptide SEQ ID NO	5 . . . 507	396/503 (78%)
	40536 - Drosophila
	melanogaster, 537 aa.
	[WO200171042-A2,
	27-SEP-2001]
AAM80117	Human protein SEQ ID NO	152 . . . 546	298/404 (73%)	e−170
	3763 - Homo sapiens, 420 aa.	1 . . . 401	332/404 (81%)
	[WO200157190-A2,
	09-AUG-2001]
AAB56844	Human prostate cancer	292 . . . 543	217/252 (86%)	e−125
	antigen protein sequence	33 . . . 284	230/252 (91%)
	SEQ ID NO: 1422 - Homo
	sapiens, 315 aa.
	[WO200055174-A1,
	21-SEP-2000]
ABB89473	Human polypeptide SEQ ID NO	301 . . . 543	209/243 (86%)	e−121
	1849 - Homo sapiens,	1 . . . 243	222/243 (91%)
	274 aa. [WO200190304-A2,
	29-NOV-2001]

[0411] 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 8E.

TABLE 8E
Public BLASTP Results for NOV8a
		NOV8a	Identities/
Protein		Residues/	Similarities for
Accession	Protein/	Match	the Matched	Expect
Number	Organism/Length	Residues	Portion	Value
Q8TDW1	ST7L isoform 4 -	1 . . . 555	549/555 (98%)	0.0
	Homo sapiens	1 . . . 555	552/555 (98%)
	(Human), 555 aa.
Q8TDW4	ST7L isoform 1 -	1 . . . 544	538/544 (98%)	0.0
	Homo sapiens	1 . . . 544	541/544 (98%)
	(Human), 575 aa.
Q8TDW3	ST7L isoform 2 -	1 . . . 544	521/544 (95%)	0.0
	Homo sapiens	1 . . . 527	524/544 (95%)
	(Human), 558 aa.
Q8K4P7	Tumorsuppressor	1 . . . 555	501/559 (89%)	0.0
	St7-like product -	1 . . . 559	529/559 (94%)
	Mus musculus
	(Mouse), 559 aa.
Q8TDW2	ST7L isoform 3 -	1 . . . 544	508/544 (93%)	0.0
	Homo sapiens	1 . . . 513	510/544 (93%)
	(Human), 544 aa.

[0412] PFam analysis predicts that the NOV8a protein contains the domains shown in the Table 8F.

TABLE 8F
Domain Analysis of NOV8a
		Identities/
		Similarities
	NOV8a	for the Matched
Pfam Domain	Match Region	Region	Expect Value

Example 9

[0413] 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: 69            760 bp
NOV9a,       AATCGCCCTTCATCATGCTATTACAATCCCAAACCATGGGGGTTTCTCACAGCTTTACACCAAAGGGC
CG160152-01
DNA Sequence ATCACTATCCCTCAAAGAGAGAAACCTGGACACATGTACCAAAACGAAGATTACCTGCAGAACGGGCT
             GCCAACAGAAACCACCGTTCTTGGGACAGTCCAGATCCTGTGTTGCCTGTTGATTTCAAGTCTGGGGG
             CCATCTTGGTTTTTGCTCCCTACCCCTCCCACTTCAATCCAGCAATTTCCACCACTTTGATGTCTGGG
             TACCCATTTTTAGGAGCTCTGTGTTTTGGCATTACTGGATCCCTCTCAATTATCTCTGGAAAACAATC
             AACTAAGCCCTTTGACCTGAGCAGCTTGACCTCAAATGCAGTGAGTTCTGTTACTGCAGGAGCAGGCC
             TCTTCCTCCTTGCTGACAGCATGGTAGCCCTGAGGACTGCCTCTCAACATTGTGGCTCAGAAATGGAT
             TATCTATCCTCATTGCCTTATTCGGAGTACTATTATCCAATATATGAAATCAAAGATTGTCTCCTGAC
             CAGTGTCAGTTTAACAGGTGTCCTAGTGGTGATGCTCATCTTCACTGTGCTGGAGCTCTTATTAGCTG
             CATACAGTTCTGTCTTTTGGTGGAAACAGCTCTACTCCAACAACCCTGGGAGTTCATTTTCCTCGACC
             CAGTCACAAGATCATATCCAACAGGTCAAAAAGAGTTCTTCACGGTCTTGGATATAAGTAACTCTTGG
             CCTCAGAGGAAG
             ORF Start: ATG at 15                    ORF Stop: TAA at 735
             SEQ ID NO: 70            240 aa         MW at 26130.7kD
NOV9a,       MLLQSQTMGVSHSFTPKGITIPQREKPGHMYQNEDYLQNGLPTETTVLGTVQILCCLLISSLGAILVF
CG160152-01
Protein      APYPSHFNPAISTTLMSGYPFLGALCFGITGSLSIISGKQSTKPFDLSSLTSNAVSSVTAGAGLFLLA
Sequence
             DSMVALRTASQHCGSEMDYLSSLPYSEYYYPIYEIKDCLLTSVSLTGVLVVMLIFTVLELLLAAYSSV
             FWWKQLYSNNPGSSFSSTQSQDHIQQVKKSSSRSWI
             SEQ ID NO: 71            240 aa         MW at 26130.7kD
NOV9b,       CTTCATCATGCTATTACAATCCCAAACCATGGGGGTTTCTCACAGCTTTACACCAAAGGGCATCACT
CG160152-03
DNA Sequence ATCCCTCAAAGAGAGAAACCTGGACACATGTACCAAAACGAAGATTACCTGCAGAACGGGCTGCCAA
             CAGAAACCACCGTTCTTGGGGACCTGAGCAGCTTGACCTCAAATGCAGTGAGTTCTGTTACTGCAGG
             AGCAGGCCTCTTCCTCCTTGCTGACAGCATGGTAGCCCTGAGGACTGCCTCTCAACATTGTGGCTCA
             GAAATGGATTATCTATCCTCATTGCCTTATTCGGACTACTATTATCCAATATATGAAATCAAAGATT
             GTCTCCTGACCAGTGTCAGTTTAACAGGTGTCCTAGTGGTGATGCTCATCTTCACTGTGCTGGAGCT
             CTTATTAGCTGCATACAGTTCTGTCTTTTGGTGGAAACAGCTCTACTCCAACAACCCTGGGAGTTCA
             TTTTCCTCGACCCAGTCACAAGATCATATCCAACAGGTCAAAAAGAGTTCTTCACGGTCTTGGATAT
             AAGTAACTCTTGGCCTCAGAGGAAGGAAAAGCAACTCAACACTCATGGTCAAGTGTGATTAGACTTT
             CCTGAAATCTCTGCC
             ORF Start: ATG at 8                     ORF Stop: TAA at 536
             SEQ ID NO: 72            176 aa         MW at 19453.9kD
NOV9b,       MLLQSQTMGVSHSFTPKGITIPQREKPGHMYQNEDYLQNGLPTETTVLGDLSSLTSNAVSSVTAGAG
CG160152-03
Protein      LFLLADSMVALRTASQHCGSEMDYLSSLPYSEYYYPIYEIKDCLLTSVSLTGVLVVMLIFTVLELLL
Sequence
             AAYSSVFWWKQLYSNNPGSSFSSTQSQDHIQQVKKSSSRSWI
             SEQ ID NO: 73            675 bp
NOV9c,       CTTCATCATGCTATTACAATCCCAAACCATGGGGGTTTCTCACAGCTTTACACCAAAGGGCATCACTA
CG160152-02
DNA Sequence TCCCTCAAAGAGAGAAACCTGGACACATGTACCAAAACGAACATTACCTGCAGAACGGGCTGCCAACA
             GAAACCACCGTTCTTGGGTTTGGCATTACTGGATCCCTCTCAATTATCTCTGGAAAACAATCAACTAA
             GCCCTTTGACCTGAGCAGCTTGACCTCAAATGCAGTGAGTTCTGTTACTGCAGGAGCAGGCCTCTTCC
             TCCTTGCTGACAGCATGGTAGCCCTGAGGACTGCCTCTCAACATTGTGGCTCAGAAATGGATTATCTA
             TCCTCATTGCCTTATTCGGAGTACTATTATCCAATATATGAAATCAAAGATTGTCTCCTGACCAGTGT
             CAGTTTAACAGGTGTCCTAGTGGTGATGCTCATCTTCACTGTGCTGGAGCTCTTATTAGCTGCATACA
             GTTCTGTCTTTTGGTGGAAACAGCTCTACTCCAACAACCCTGGGAGTTCATTTTCCTCGACCCAGTCA
             CAAGATCATATCCAACAGGTCAAAAAGAGTTCTTCACGGTCTTGGATATAAGTAACTCTTGGCCTCAG
             AGGAAGGAAAAGCAACTCAACACTCATGGTCAAGTGTGATTAGACTTTCCTGAAATCTCTGCC
             ORF Start: ATG at 8                     ORF Stop: TAA at 593
             SEQ ID NO: 74            195 aa         MW at 21404.1kD
NOV9c,       MLLQSQTMGVSHSFTPKGITIPQREKPGHMYQNEDYLQNGLPTETTVLGFGITGSLSIISGKQSTKPF
CG160152-02
Protein      DLSSLTSNAVSSVTAGAGLFLLADSMVALRTASQHCGSEMDYLSSLPYSEYYYPIYEIKDCLLTSVSL
Sequence
             TGVLVVMLIFTVLELLLAAYSSVFWWKQLYSNNPGSSFSSTQSQDHIQQVKKSSSRSWI
             SEQ ID NO: 75            675 bp
NOV9d,       CTTCATCATGCTATTACAATCCCAAACCATGGGGGTTTCTCACAGCTTTACACCAAAGGGCATCACT
CG1600152-04
Protein      ATCCCTCAAAGAGAGAAACCTQGACACATGTACCAAAACGAAGATTACCTGCAGAACGGGCTGCCAA
DNA Sequence
             CAGAAACCACCGTTCTTCGGTTTGGCATTACTGGATCCCTCTCAATTATCTCTGGAAAACAATCAAC
             TAAGCCCTTTGACCTGACCAGCTTGACCTCAAATGCAGTGAGTTCTGTTACTGCAGGAGCAGGCCTC
             TTCCTCCTTGCTGACAGCATGGTAGCCCTGAGGACTGCCTCTCAACATTGTGGCTCAGAAATGGATT
             ATCTATCCTCATTGCCTTATTCGGAGTACTATTATCCAATATATGAAATCAAAGATTGTCTCCTGAC
             CAGTGTCAGTTTAACAGGTGTCCTAGTGGTGATGCTCATCTTCACTGTGCTGGAGCTCTTATTAGCT
             GCATACAGTTCTGTCTTTTGGTGGAAACAGCTCTACTCCAACAACCCTCGGAGTTCATTTTCCTCGA
             CCCAGTCACAAGATCATATCCAACAGGTCAAAAAGAGTTCTTCACGGTCTTGGATATAAGTAACTCT
             TGGCCTCAGAGGAAGGAAAAGCAACTCAACACTCATGGTCAAGTGTGATTAGACTTTCCTGAAATCT
             CTGCC
             ORF Start: ATG at 8                     ORF Stop: TAA at 593
             SEQ ID NO: 76            195 aa         MW at 21404.1kD
NOV9d,       MLLQSQTMGVSHSFTPKGITIPQREKPGHMYQNEDYLQNGLPTETTVLGFGITGSLSIISGKQSTKP
CG160152-04
Protein      FDLSSLTSNAVSSVTAGAGLFLLADSMVALRTASQHCGSEMDYLSSLPYSEYYYPIYEIKDCLLTSV
Sequence
             SLTGVLVVMLIFTVLELLLAAYSSVFWWKQLYSNNPGSSFSSTQSQDHIQQVKKSSSRSWI
             SEQ ID NO: 77            747 bp
NOV9e,       CACCGCGGCCGCACCATGCTATTACAATCCCAAACCATGGGGGTTTCTCACAGCTTTACACCAAAGGG
CG160152-05
DNA Sequence CATCACTATCCCTCAAAGAGAGAAACCTGGACACATGTACCAAAACGAAGATTACCTGCAGAACGGGC
             TGCCAACAGAAACCACCGTTCTTGGGACTGTCCAGATCCTGTGTTGCCTGTTGATTTCAAGTCTGGGG
             GCCATCTTGGTTTTTGCTCCCTACCCCTCCCACTTCAATCCAGCAATTTCCACCACTTTGATGTCTGG
             GTACCCATTTTTAGGAGCTCTGTGTTTTGGCATTACTGGATCCCTCTCAATTATCTCTGGAAAACAAT
             CAACTAAGCCCTTTGACCTGAGCAGCTTGACCTCAAATGCAGTGAGTTCTGTTACTGCAGGAGCAGGC
             CTCTTCCTCCTTGCTGACAGCATGGTAGCCCTGAGGACTGCCTCTCAACATTGTGGCTCAGAAATGGA
             TTATCTATCCTCATTGCCTTATTCGGAGTACTATTATCCAATATATGAAATCAAAGATTGTCTCCTGA
             CCAGTGTCAGTTTAACAGGTGTCCTAGTGGTGATGCTCATCTTCACTGTGCTGGAGCTCTTATTAGCT
             GCATACAGTTCTGTCTTTTGGTGGAAACAGCTCTACTCCAACAACCCTGGGAGTTCATTTTCCTCGAC
             CCAGTCACAAGATCATATCCAACAGGTCAAAAAGAGTTCTTCACGGTCTTGGATATAGGTCGACCGC
             ORF Start:ATG at 16                     ORF Stop: TAG at 736
             SEQ ID NO: 78            240 aa         MW at 26130.7kD
NOV9e,       MLLQSQTMGVSHSFTPKGITIPQREKPGHMYQNEDYLQNGLPTETTVLGTVQILCCLLISSLGAILVF
CG160152-05
Protein      APYPSHFNPAISTTLMSGYPFLGALCFGITGSLSIISGKQSTKFDLSSLTSNAVSSVTAGAGLFLLA
Sequence
             DSMVALRTASQHCGSEMDYLSSLPYSEYYYPIYEIKDCLLTSVSLTGVLVVMLIFTVLELLLAAYSSV
             FWWKQLYSNNPGSSFSSTQSQDHIQQVKKSSSRSWI

[0414] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 9B.

TABLE 9B
Comparison of NOV9a against NOV9b through NOV9e.
	NOV9a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV9b	114 . . . 240	127/127 (100%)
	50 . . . 176	127/127 (100%)
NOV9c	1 . . . 240	195/240 (81%)
	1 . . . 195	195/240 (81%)
NOV9d	1 . . . 240	195/240 (81%)
	1 . . . 195	195/240 (81%)
NOV9e	1 . . . 240	240/240 (100%)
	1 . . . 240	240/240 (100%)

[0415] Further analysis of the NOV9a protein yielded the following properties shown in Table 9C.

TABLE 9C
Protein Sequence Properties NOV9a
SignalP analysis:	Cleavage site between residues 70 and 71
PSORT II	PSG: a new signal peptide prediction method
analysis:	N-region: length 0; pos.chg 0; neg.chg 0
	H-region: length 16; peak value 5.27
	PSG score: 0.87
	GvH: von Heijne's method for signal seq. recognition
	GvH score (threshold: −2.1): −4.91
	possible cleavage site: between 13 and 14
	>>> Seems to have no N-terminal signal peptide
	ALOM: Klein et al's method for TM region allocation
	Init position for calculation: 1
	Tentative number of TMS(s) for the threshold 0.5: 4
	INTEGRAL	Likelihood = −10.19	Transmembrane	53-69
	INTEGRAL	Likelihood = −1.91	Transmembrane	89-105
	INTEGRAL	Likelihood = −1.49	Transmembrane	126-142
	INTEGRAL	Likelihood = −11.30	Transmembrane	184-200
	PERIPHERAL	Likelihood = 9.02 (at 167)
	ALOM score:	−11.30 (number of TMSs: 4)
	MTOP: Prediction of membrane topology (Hartmann et al.)
	Center position for calculation: 60
	Charge difference: 3.5 C( 0.5) − N(−3.0)
	C > N: C-terminal side will be inside
	>>>Caution: Inconsistent mtop result with signal peptide
	>>> membrane topology: type 3b
	MITDISC: discrimination of mitochondrial targeting seq
	R content:	1	Hyd Moment (75):	4.11
	Hyd Moment (95):	1.37	G content:	2
	D/E content:	1	S/T content:	6
	Score:	−4.06
	Gavel: prediction of cleavage sites for mitochondrial preseq
	cleavage site motif not found
	NUCDISC: discrimination of nuclear localization signals
	pat4: none
	pat7: none
	bipartite: none
	content of basic residues: 4.6%
	NLS Score: −0.47
	KDEL: ER retention motif in the C-terminus: none
	ER Membrane Retention Signals: none
	SKL: peroxisomal targeting signal in the C-terminus: none
	PTS2: 2nd peroxisomal targeting signal: none
	VAC: possible vacuolar targeting motif: none
	RNA-binding motif: none
	Actinin-type actin-binding motif:
	type 1: none
	type 2: none
	NMYR: N-myristoylation pattern: none
	Prenylation motif: none
	memYQRL: transport motif from cell surface to Golgi: none
	Tyrosines in the tail: none
	Dileucine motif in the tail: none
	checking 63 PROSITE DNA binding motifs: none
	checking 71 PROSITE ribosomal protein motifs: none
	checking 33 PROSITE prokaryotic DNA binding motifs: none
	NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination
	Prediction: cytoplasmic
	Reliability: 55.5
	COIL: Lupas's algorithm to detect coiled-coil regions
	total: 0 residues
Final Results (k = 9/23):
44.4%: endoplasmic reticulum
22.2%: vacuolar
11.1%: Golgi
11.1%: vesicles of secretory system
11.1%: mitochondrial
>> prediction for CG160152-01 is end (k = 9)

[0416] A search of the NOV9a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 9D.

TABLE 9D
Geneseq Results for NOV9a
		NOV9a
		Residues/	Identities/
Geneseq	Protein/Organism/Length	Match	Similarities for the	Expect
Identifier	[Patent #, Date]	Residues	Matched Region	Value
ABP65232	Hypoxia-regulated protein	1 . . . 240	240/240 (100%)	e−136
	[WO200246465-A2,	1 . . . 240	240/240 (100%)
	13-JUN-2002]
ABP65029	Human membrane spanning	1 . . . 240	240/240 (100%)	e−136
	4-domain family, subfamily	1 . . . 240	240/240 (100%)
	A 7 protein - Homo sapiens,
	240 aa. [WO200262946-A2,
	15-AUG-2002]
AAM93537	Human polypeptide, SEQ ID	1 . . . 240	240/240 (100%)	e−136
	NO: 3283 - Homo sapiens,	1 . . . 240	240/240 (100%)
	240 aa. [EP1130094-A2,
	05-SEP-2001]
AAM78610	Human protein SEQ ID NO:	1 . . . 240	240/240 (100%)	e−136
	1272 - Homo sapiens, 240 aa.	1 . . . 240	240/240 (100%)
	[WO200157190-A2,
	09-AUG-2001]
AAE13063	Human CD20/IgE-receptor	1 . . . 240	240/240 (100%)	e−136
	like protein, agp-69406-al -	1 . . . 240	240/240 (100%)
	Homo sapiens, 240 aa.
	[WO200174903-A2,
	11-OCT-2001]

[0417] 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 9E.

TABLE 9E
Public BLASTP Results for NOV9a
		NOV9a
Protein		Residues/	Identities/
Accession		Match	Similarities for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
Q9GZW8	MS4A7	1 . . . 240	240/240 (100%)	e−135
	(CD20/FC-epsilon-RI-beta	1 . . . 240	240/240 (100%)
	family member 4) (Four-span
	transmembrane protein 2)
	(Membrane-spanning
	4-domains, subfamily A,
	member 7) (High affinity
	immunoglobulin epsilon
	receptor beta subunit) - Homo
	sapiens (Human), 240 aa.
Q99N04	MS4A7 protein - Mus	1 . . . 234	126/234 (53%)	1e−61
	musculus (Mouse), 234 aa.	1 . . . 231	155/234 (65%)
Q8R3W1	Similar to RIKEN	1 . . . 234	124/234 (52%)	5e−61
	cDNA 9130422I10 gene - Mus	1 . . . 231	154/234 (64%)
	musculus (Mouse), 234 aa.
Q9D2W6	9130422I10Rik protein - Mus	1 . . . 234	112/234 (47%)	6e−51
	musculus (Mouse), 215 aa.	1 . . . 212	141/234 (59%)
Q99N07	MS4A6D protein (RIKEN	2 . . . 235	84/234 (35%)	5e−35
	cDNA 1110058E16 gene) -	5 . . . 235	130/234 (54%)
	Mus musculus (Mouse), 247
	aa.

[0418] PFam analysis predicts that the NOV9a protein contains the domains shown in the Table 9F.

TABLE 9F
Domain Analysis of NOV9a
		Identities/
		Similarities
	NOV9a	for the Matched
Pfam Domain	Match Region	Region	Expect Value

EXAMPLE 10

[0419] 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: 79            1257 bp
NOV10a,           GTCCCGCCCCTGCCCGGCCTGGCCCCGCCCCTGCCCGGCCCCGCCCCCCAACGTGTCTTCAGGTCTC
CG160185-01
DNA Sequence      TTTCCCTCCACCCGGCCCTTAGGACCGCTGTTCGACGTGCTCGTGAGTCCTTCGCCTGTCTGCCTTC
                  CACCTCTCTGCAGCTCCTTCTCCAATCTCATGGTCTTCTTGAQCTTGGCCGCCCTCCACGCCCCATG
                  CTGGGCTTCGTCCGTTCTGGGGTCTACCTCTCTGGCTTCATCCCTCCCACAGTTTCGAGGGTTTCCC
                  TGTGCTCAGCCCCCTGGCAGCCGCCCCCTGTGCAGACCACTGGGCAGATCCAGCTGACCTCCAGGGG
                  CACTTCCTCCCCTCATCACTGGGCCGGTGCTCTGCAGAATGAGCTGTGAGAGCCACTGTGGCTGGCC
                  AGACGGTGCCACTCACAGTCACTTCAGACTCACACGAGCCTTCGTCCCGACCCCTGCATTCATCTGT
                  GTTCTGTTTTATGTTTTTTCCCAGTCACCTGAGCTGCACGCCTTCGTCACCCCAGACTCCTCCCTCC
                  TGTCACCCTTATCCTCACCCCAGCACCTTTACGTCTGCCCCAQGCTCCATTTCCCCCTCTTCTGCCT
                  GGATCAAACCACCCTGACTTTCCTOGGTCTTCGTGCAACAGCCTGCTCCGGCCGCTGCCTCACTGCA
                  CCTGCAAATCCACTTGCACCCACACCCAGGCCACGGTTTTTAAACAGAAGCCTCAGCAGATCCCTCT
                  CTCTGGCCAGCTCCCTGTTGAACCACGAAGCACGTCCCTGTTGAACCTCAGCATCACCCGCCCCCAC
                  CCCTGCATCCCACTTCTGCTCTGGGAGCCTCTCGGTTCCTGGGCGCACCTGCTGCCCTTCCCTGTTT
                  GTCACTGGGTGACCTCCCGTCCTTGTGGGCGCTCCCGGGCCCTGGTCTCGCGCCTTCTGAGGACTTG
                  CTCTCCTGGTAGCGGCTGCTCACTGTGAGCCCAGAGAGCAGGCGTGGCTGTTGACCTTAGGTCCTCC
                  CAGAACCTGGCGGATCGCCTGGCTCCCAGGCACGAGGCGCTGCATGACGCCTCCAACTTCCGCCAAT
                  CTAGCCCAAGGATGGCGTTCTAAATAAAACGCGTTCTACAGAAAAGTGTTTATTGCATTCTTCTTTG
                  AAATAATGTAAGCATAAAAGTAATCTGAATATTGACCAATAGGGTTAATTGATTAAGGTATATTTAC
                  CTAATTGAAATATTGGGTAGATGTGAAAAAAAGTTCCAATGTTTGTAATTA
                  ORF Start: ATG at 374                   ORF Stop: TGA at 779
                  SEQ ID NO: 80            135 aa         MW at 14547.5kD
NOV10a,           MSCESHCGWPEGATHSHFRLTGAFVPTPAFICVLFYVFSQSPELQALVTPDSSLLSPLSSPQHLYVC
CG160185-01
Protein Sequences PRLHFPLFCLDQTTLTFLGLRATACSGRCLTAPANPLAPTPRPGFLNRSLSRSLSLASSLLNQEAGP
                  C

[0420] Further analysis of the NOV10a protein yielded the following properties shown in Table 10B.

TABLE 10B
Protein Sequence Properties NOV10a
SignalP analysis:	No Known Signal Sequence Predicted
PSORT II	PSG: a new signal peptide prediction method
analysis:	N-region: length 11; pos.chg 0; neg.chg 2
	H-region: length 7; peak value 0.00
	PSG score: −4.40
	GvH: von Heijne's method for signal seq. recognition
	GvH score (threshold: −2.1): −3.68
	possible cleavage site: between 46 and 47
	>>> Seems to have no N-terminal signal peptide
	ALOM: Klein et al's method for TM region allocation
	Init position for calculation: 1
	Tentative number of TMS(s) for the threshold 0.5: 1
	Number of TMS(s) for threshold 0.5: 1
	INTEGRAL Likelihood = −3.03 Transmembrane 22-38
	PERIPHERAL Likelihood = 5.99 (at 71)
	ALOM score: −3.03 (number of TMSs: 1)
	MTOP: Prediction of membrane topology (Hartmann et al.)
	Center position for calculation: 29
	Charge difference: −3.5 C( −2.0) − N( 1.5)
	N >= C: N-terminal side will be inside
	>>> membrane topology: type 2 (cytoplasmic tail 1 to 22)
	MITDISC: discrimination of mitochondrial targeting seq
	R content:	0	Hyd Moment(75):	4.85
	Hyd Moment(95):	2.00	G content:	1
	D/E content:	2	S/T content:	2
	Score:	−7.58
	Gavel: prediction of cleavage sites for mitochondrial preseq
	cleavage site motif not found
	NUCDISC: discrimination of nuclear localization signals
	pat4: none
	pat7: none
	bipartite: none
	content of basic residues: 5.2%
	NLS Score: −0.47
	KDEL: ER retention motif in the C-terminus: none
	ER Membrane Retention Signals: none
	SKL: peroxisomal targeting signal in the C-terminus: none
	PTS2: 2nd peroxisomal targeting signal: none
	VAC: possible vacuolar targeting motif: none
	RNA-binding motif: none
	Actinin-type actin-binding motif:
	type 1: none
	type 2: none
	NMYR: N-myristoylation pattern: none
	Prenylation motif: none
	memYQRL: transport motif from cell surface to Golgi: none
	Tyrosines in the tail: none
	Dileucine motif in the tail: none
	checking 63 PROSITE DNA binding motifs: none
	checking 71 PROSITE ribosomal protein motifs: none
	checking 33 PROSITE prokaryotic DNA binding motifs: none
	NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination
	Prediction: nuclear
	Reliability: 89
	COIL: Lupas's algorithm to detect coiled-coil regions
	total: 0 residues
Final Results (k = 9/23):
39.1%: nuclear
26.1%: mitochondrial
8.7%: Golgi
8.7%: cytoplasmic
4.3%: extracellular, including cell wall
4.3%: plasma membrane
4.3%: vesicles of secretory system
4.3%: peroxisomal
>> prediction for CG160185-01 is nuc (k = 23)

[0421] A search of the NOV10a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 10C.

TABLE 10C
Geneseq Results for NOV10a
		NOV10a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAY44775	Long splice variant of human	1 . . . 110	31/110 (28%)	0.82
	Enovin - Homo sapiens, 228	8 . . . 100	36/110 (32%)
	aa. [WO200004050-A2,
	27-JAN-2000]
AAY93559	A human GDNF-related	1 . . . 110	31/110 (28%)	0.82
	neurotropic factor 4 (GRNF4) -	8 . . . 100	36/110 (32%)
	Homo sapiens, 228 aa.
	[WO200034475-A2,
	15-JUN-2000]
AAG48263	Arabidopsis thaliana protein	20 . . . 85	17/66 (25%)	5.4
	fragment SEQ ID NO: 60928 -	131 . . . 187	31/66 (46%)
	Arabidopsis thaliana, 333
	aa. [EP1033405-A2,
	06-SEP-2000]
AAG48262	Arabidopsis thaliana protein	20 . . . 85	17/66 (25%)	5.4
	fragment SEQ ID NO: 60927 -	145 . . . 201	31/66 (46%)
	Arabidopsis thaliana, 347
	aa. [EP1033405-A2,
	06-SEP-2000]
AAG48261	Arabidopsis thaliana protein	20 . . . 85	17/66 (25%)	5.4
	fragment SEQ ID NO: 60926 -	227 . . . 283	31/66 (46%)
	Arabidopsis thaliana, 429
	aa. [EP1033405-A2,
	06-SEP-2000]

[0422] In a BLAST search of public sequence datbases, the NOV10a protein was found to have homology to the proteins shown in the BLASTP data in Table 10D.

TABLE 10D
Public BLASTP Results for NOV10a
		NOV10a	Identities/
Protein		Residues/	Similarities for
Accession	Protein/Organism/	Match	the Matched	Expect
Number	Length	Residues	Portion	Value
Q22001	Hypothetical	15 . . . 118	31/107 (28%)	8.6
	28.5 kDa protein -	131 . . . 232	45/107 (41%)
	Caenorhabditis
	elegans, 247 aa.

[0423] PFam analysis predicts that the NOV10a protein contains the domains shown in the Table 10E.

TABLE 10E
Domain Analysis of NOV10a
		Identities/
		Similarities
	NOV10a	for the Matched
Pfam Domain	Match Region	Region	Expect Value

Example 11

[0424] 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: 81            14877 bp
NOV11a,          GCCCTCAGCATCGGACCAGAGTACTTGGTATCTGGATGAATCGACACTCACTGACAACATCAAAAAG
CG160244-01
DNA Sequence     ACACTGCACAAGTTCTGTGGCCCCTCCCCTGTGGTCTTCAGTGATGTGAACTCCATGTATCTGTCTT
                 CCACGGAGCCGCCAGCCGCTGCTGAATGGOCATGTCTGCTGCGCCCTCTGAGGGGCCGTGAGCCAGA
                 GGGCGTCTGGAACCTGCTAAGCATTQTGCGGCAGATGTTCAAGCGGAGGGACAGCAATGCTGCCCCC
                 TTGTTGGAAATCCTCACTGACCAGTGCCTCACCTATGAACACATAACAGGTTGGTGGTATAGCGTAC
                 GTACCTCAGCCTCACACAGCAGTGCCAGTGGGCACACGGGCCGTAGCAACGGGCAGTCAGAGGTGGC
                 AGCCCATGCCTGTGCCAGCATGTGTGACGAGATGGTCACACTGTGGAGGCTGGCCGTCCTGGACCCT
                 GCACTCAGCCCCCAGCGGCGCCGGCAACTGTGTACGCAGCTGCGGCAGTGCCAACTGAACGTGATTG
                 AGAACGTCAAGCGGGGCCAACACAAGAAGACGCTGGAGCGGCTCTTCCCCGGCTTCCCGCCAGCCGT
                 GGAGGCCTGCTACTTCAACTGGGAAGACGCCTACCCACTTCCTGGTGTCACCTACAGCGGCACTGAC
                 AGGAAGCTGGCACTGTGCTGGGCCCGGGCCCTGCCCTCTCGGCCAGGTGCCTCCCGCTCTOGGGCCC
                 TGGAGGAATCCCGGGACCGGCCCCGACCCCTTCCTACTGAGCCAGCTGTGCGGCCCAAGGAGCCTGG
                 GACCAAGCGAAAGGGCTTGGGTGAGCGCGTCCCCTCATCACAGCGGGGTCCCCGCCGCCTCTCAGCT
                 GAAGGCGGAGATAAAGCTCTACATAAGATGGGTCCACGTGGGGGCAAAGCCAAGGCACTGGGTGGGG
                 CTGGCAGTGGGAGCAAGGGCTCAGCAGGTGGCGGAAGCAAGCGACGGCTGAGCAGCGAAGACAGCTC
                 CCTGGAGCCAGACCTGGCCCAGATGAGCCTCGATGACAGCAGCCTGGCCCTGGGCGCAGAGGCCAGC
                 ACCTTCGGGGGATTCCCTGAGAGCCCTCCACCCTGTCCTCTCCACGGTGGCTCCCGAGGCCCTTCCA
                 CTTTCCTTCCTGAGCCCCCAGATACTTATGAAGAAGATGGTGGTGTGTACTTCTCGGAAGGGCCTGA
                 GCCTCCCACAGCCTCTGTTGGCCCCCCTGGCCTACTGCCTGGCGATGTCTGTACCCAGGACGACCTC
                 CCTTCTACAGATGAGAGTGGCAATCCGCTTCCCAAAACCAAAGAGGCAGCCCCTGCAGTTGGAGAGG
                 AGGATGATCACTACCAGGCQTACTATCTGAATGCCCAGGATGGGGCTGGGGGCGAGGAAGAGAACGC
                 CGAGGGCGGCGATGGGGAGGAGCACGACCTGTTTGCTGGGCTGAAGCCACTGGAACAGGAGAGTCGC
                 ATGGAGGTACTQTCTGCCTGTGCTGAGGCCCTGCATGCGCATGGCTATAGCAGTGAGGCCTCCCGTC
                 TCACTGTGCAGCTTGCCCAGGATCTGCTAGCCAACCCACCCGACCTCAAGGTAGAGCCGCCCCCTGC
                 CAAGGGCAAGAAGAACAAGGTATCCACGAGCCGTCACACCTGGGTGGCTACCAACACCCTGAGCAAG
                 GCGGCCTTCCTGTTGACAGTGCTAAGTGAGCGTCCAGACCACCACAACCTGGCCTTCCGAGTTGGCA
                 TGTTTGCCTTGGAGCTACAGAGCCCTCCAGCTTCTACCAAGGCCTTCGAGGTGAAGCTGGCATACCA
                 GGAGTCTGAGGTGGCTGCCCTGCTCAAGAACATCCCTCTGGGTCCAAGTGAGATGAGTACCATGCGG
                 TGCCGGGCAGAGGAACTTCGGGAGCGGACACTCTGTGACTATCGGCCTGTGTTGCCTCTCATGCTGG
                 CCAGTTTCATCTTTGACGTTCTCTGTGCTCCAGTGGTTTCTCCCACAGGTTCCCGGCCCCCAAGTCG
                 CAACTGGAACAGCGAGACACCTGGGGATQACGAGCTTGGATTTGAAGCAGCAGTTGCTGCCTTGGGC
                 ATGAAGACAACAGTGAGCGAGGCAGAACATCCCCTCTTATGTGAAGGCACACGTCGGGAGAAGGGTG
                 ACCTGGCATTAGCACTAATGATCACTTACAACGACGACCAGCCCAAGCTTAAGAAGATCTTAGACAA
                 ACTCTTGGACCGAGAGAGCCAGACACATAAGCCACAGACGCTGAGTTCTTTCTACTCATCTAGCCGC
                 CCAACCACAGCCAGCCAGACGTCTCCTTCAAAGCACGGGGGCCCATCTQCCCCAGGGACCCTGCAAC
                 CACTGACCTCAGGCTCTGCAGGGCCTGCTCAACCACGGAGTGTCGCAGCGGCTGGGCCAGGCCCCAC
                 TGAGGGCTTCACAGAGAAGAATGTGCCTGAGAGTTCCCCACATTCCCCCTGTGAGGGTCTTCCATCT
                 GAGGCAGCTTTGACCCCAAGGCCAGAACGGAAGGTTCCTAGCCGCTTGGCACTTGGCAGTCGTCGAG
                 GCTATAATGGACGGGGATGGGGGTCCCCAGGACGGCCTAAGAAGAAGCACACAGGCATGGCCAGCAT
                 TGACAGCAGTGCCCCTGAAACAACATCQGATAGTTCCCCCACCTTAAGCCCGAGACCACTTCAAGGG
                 GGCTGGGCCCCCACCTCCTCGGGTCGAGGTCAGGACAGTGACAGCATTAGCAACTCTTCTTCGGACT
                 CCCTCGGCTCCTCATCCTCCAGTGCAAGTCGCCGGGCCAGTCCCAGTGGAGGAGCCCGGGCGAAGAC
                 TGTTGAAGTTGGCACGTACAAGGGCCGCCGCCCCCAGAGTCATGCCCCTCATGTACCCAATCAGCCA
                 TCAGAGGCAGCTGCACACTTCTACTTCGAGCTGGCGAAGACAGTGCTGATCAAGACAGGGGGCAACA
                 GCAGCACTTCCATTTTCACACATCCATCTTCCTCAGGGGGCCACCAGGGTCCTCACCGCAACCTGCA
                 CCTTTGCGCCTTCGAGATTGGGCTTTATGCCCTTGGCCTGCACAACTTTGTTTCTCCCAACTGGCTC
                 TCACCTACTTATTCTTCCCACGTTTCCTGGATTACAGGCCACGCCATGGACATAQGCAGCGCAGCCC
                 TGACTATACTGGTAGAATGCTGGGATGGGCACCTGACACCCCCTCAGGTTGCATCCCTGGCTGACAG
                 GGCATCACCGGCAAGAGACTCCAATATGGTGACGGCCGCAGCAGAGCTGGCCCTGAGCTGCCTGCCT
                 CACGCCCATGCATTQAACCCTAATQAGATCCAGCCGGCCCTCGTGCAGTGCAAGGAACAGGACAACC
                 TGATGTTGGAGAAGGCCTGCATGGCAGTGGAAGAGGCAGCTAAGGGTGGGGGCGTGTACCCTGAAGT
                 GTTGTTTGAGGTTGCTCACCAGTGQTTCTGGCTATATGAGCAAACTGCAGCTGGCTCATCCACAGCC
                 CGTGAAGGGGCTACAAGCTGTAGTGCCAGTGGGATCAGGGCAGGTGGGGAAGCTGGGCGGGGTATGC
                 CTGAGGGTAGAGGGGGCCCAGGGACTGAGCCGGTTACAGTGGCAGCGGCAGCAGTGACAGCAGCAGC
                 CACAGTCGTGCCCGTCATATCGGTGGGGTCTAGTTTATACCCGGGTCCAGGACTGGGGCATGGCCAC
                 TCCCCTGGCCTGCACCCCTACACTGCTCTACAGCCCCACCTGCCCTGTACCCCTCAGTATCTCACTC
                 ACCCAGCTCACCCTGCCCACCCCATGCCTCACATGCCCCGGCCTGCCGTCTTCCCTGTGCCCACCTC
                 TGCATACCCACAGGGTGTGCATCCTGCATTCCTAGGCGCTCAGTACCCTTATTCAGTGACTCCTCCC
                 TCACTTCCTGCCACTGCTGTGTCTTTCCCCGTTCCTTCCATGGCACCCATCACAGTACATCCCTACC
                 ACACAGAGCCACGGCTTCCACTGCCCACCAGTGTGGCCTTGAGCAGTGTCCATCCAGCATCCACGTT
                 TCCAGCCATCCAAGGTGCCTCACTGCCTGCCCTGACCACACAGCCCAGCCCTCTGGTGAGCGGAGGT
                 TTTCCACCGCCCGAGGACGAGACACACAGTCAGCCAGTCAATCCCCACAGCCTGCACCACCTGCATG
                 CTGCCTACCGTGTCGGAATGCTGGCACTGGAGATGCTGGGTCGCCGGGCACACAACGATCACCCCAA
                 CAACTTCTCCCGCTCCCCCCCCTACACTGATGATGTCAAATCGTTGCTGGCCCTGCCAGCAAAGCTC
                 GGAGATCGTCATGGAGACCCTGCAGCGGCTGAGTCCCGCTCATGCCCACAACCACCTGCGTGCCCCG
                 GCCTTCCACCAACTGGTGCAGCGCTGCCAGCACGCATACATCCAGTACATCCACCACAGCTTGATTC
                 ACCTGACTCCTQCGGACTACGACGACTTTGTGAATGCGATCCGGAGTGCCCGCAGCGCCTTCTGCCT
                 GACGCCCATGCGCATCATGCAGTTCAACGACATCCTACAGAACCTCAAGCGCAGCAAACAGACCAAG
                 GAGCTGTGGCAGCGGGTCTCACTCGAQATGGCCACCTTCTCCCCCTGAGTCTTTCACCCTTAGGGTC
                 CTATACAGGGACCCAGGCCTGTGCCTATGGCGGCCCCTCACTCAGGGGGACTGAAACTTGGCTGGAC
                 AGATCATCCTCACTCAGTTCCCTGCTAGCACAGACTCACAGCTGCTCTTGGGCTATAGCTTGGGGCC
                 AAGATGTCTCACACCCTAGAAGCCTAGGGCTGGGGGAGACAGCCCTGTCTGGGAGGGGGCGTTGGGT
                 GGCCTCTGGTATTTATTTGGCATTTATAAATATATAAACTCCTTTTTTACTCT
                 ORF Start: ATG at 122                   ORF Stop: TAA at 4859
                 SEQ ID NO :82            1579 aa        MW at 166990.0kD
NOV11a,          MYLSSTEPPAAAEWACLLRPLRGREPEGVWNLLSIVREMFKRRDSNAAPLLEILTDQCLTYEQITGW
CG160244-01
Protein Sequence WYSVRTSASHSSASQHTQRSNGQSEVAAHACASMCDEMVTLWRLAVLDPALSPQRRRELCTQLRQWQ
                 LKVIENVKRGQHKKTLERLFPGFRPAVEACYFNWEEAYPLPGVTYSCTDRKLALCWARALPSRPGAS
                 RSGGLEESRDRPRPLPTEPAVRPKEPGTKRKGLGEGVPSSQRGPRRLSAEGGDKALHKMGPGGGKAK
                 ALGGAGSGSKGSAGGGSKRRLSSEDSSLEPDLAEMSLDDSSLALGAEASTFGGEPESPPPCPLHGGS
                 RGPSTFLPEPPDTYEEDCGVYFSEGPEPPTASVGPPGLLPGDVCTQDDLPSTDESGNCLPKTKEAAP
                 AVGEEDDDYQAYYLNAQDGAGGEEEKAEGGDGEEHDLFAGLKPLEQESRMEVLSACAEALHAHGYSS
                 EASRLTVELAQDLLANPPDLKVEPPPAKGKKNKVSTSRQTWVATNTLSKAAFLLTVLSERPEHHNLA
                 FRVGMFALELQRPPASTKALEVKLAYQESEVAALLKKIPLGPSEMSTMRCRAEELREGTLCDYRPVL
                 PLMLASFIFDVLCAPVVSPTGSRPPSRNWNSETPGDEELGFEAAVAALGMKTTVSEAEHPLLCEGTR
                 REKGDLALALMITYKDDQAKLKKILDKLLDRESQTHKPQTLSSFYSSSRPTTASQRSPSKHGGPSAP
                 GTLQPLTSGSAGPAQPGSVAGAGPGPTEGFTEKNVPESSPHSPCEGLPSEAALTPRPEGKVPSRLAL
                 GSRGGYNGRGWGSPGRPKKKHTGMASIDSSAPETTSDSSPTLSRRPLQGGWAPTSWGRGQDSDSISN
                 SSSDSLGSSSSSGSRRASASGGARAKTVEVGRYKGRRPESHAPHVPNQPSEAAAHFYFELAKTVLIK
                 TGGNSSTSIFTHPSSSGGHQGPHRNLHLCAFEIGLYALGLHNFVSPNWLSRTYSSHVSWITGQAMEI
                 GSAALTILVECWDCHLTPPEVASLADRASRARDSNMVRAAAELALSCLPHAHALNPNEIQRALVQCK
                 EQDNLMLEKACMAVEEAAKGGGVYPEVLFEVAHQWFWLYEQTAGGSSTAREGATSCSASGIRAGGEA
                 GRGMPEGRGGPGTEPVTVAAAAVTAAATVVPVISVGSSLYPGPGLGHGHSPGLHPYTALQPHLPCSP
                 QYLTHPAHPAHPMPHMPRPAVFPVPSSAYPQGVHPAFLCAQYPYSVTPPSLAATAVSFPVPSMAPIT
                 VHPYHTEPGLPLPTSVALSSVHPASTPPAIQGASLPALTTQPSPLVSGGPPPPEEETHSQPVNPHSL
                 HHLHAAYRVGMLALEMLQRRAHNDHPNNFSRSPPYTDDVKWLLGLAAKLGDRHGDAAAAESRSCPQP
                 PACPGLPPTGAALPAGIHAVHPPQLDSPDSCGLRRLCECDPECPQRLLPDAHGHDAVQRHPTEPQAQ
                 QTDQGAVAAGLTRDGHLLPLSLSPLGSYTGTQACGYGGPSLRGSETWLDRSSSLSSLVAQTDSCSWA
                 IAWGQDVSHPRSLGLGETALSGRGRWVASGIYLAFINI

[0425] Further analysis of the NOV11a protein yielded the following properties shown in Table 11B.

TABLE 11B
Protein Sequence Properties NOV11a
SignalP analysis:	No Known Signal Sequence Predicted
PSORT II analysis:	PSG: a new signal peptide prediction method
	N-region: length 7; pos.chg 0; neg.chg 1
	H-region: length 5; peak value 0.00
	PSG score: −4.40
	GvH: von Heijne's method for signal seq. recognition
	GvH score (threshold: −2.1): −3.08
	possible cleavage site: between 23 and 24
	>>> Seems to have no N-terminal signal peptide
	ALOM: Klein et al's method for TM region allocation
	Init position for calculation: 1
	Tentative number of TMS(s) for the threshold 0.5: 2
	INTEGRAL Likelihood = −4.51 Transmembrane 605-621
	INTEGRAL Likelihood = −3.98 Transmembrane 1156-1172
	PERIPHERAL Likelihood = 1.91 (at 966)
	ALOM score: −4.51 (number of TMSs: 2)
	MTOP: Prediction of membrane topology (Hartmann et al.)
	Center position for calculation: 612
	Charge difference: 0.0 C( 0.0) − N( 0.0)
	N >= C: N-terminal side will be inside
	>>> membrane topology: type 3a
	MITDISC: discrimination of mitochondrial targeting seq
	R content:	0	Hyd Moment(75):	4.39
	Hyd Moment(95):	4.58	G content:	0
	D/E content:	2	S/T content:	3
	Score:	−6.56
	Gavel: prediction of cleavage sites for mitochondrial preseq
	cleavage site motif not found
	NUCDISC: discrimination of nuclear localization signals
	pat4: RPKK (4) at 820
	pat4: PKKK (4) at 821
	pat4: KKKH (3) at 822
	pat7: PQRRREL (5) at 120
	pat7: PGTKRKG (4) at 227
	pat7: PPAKGKK (3) at 494
	pat7: PAKGKKN (4) at 495
	pat7: PGRPKKK (4) at 818
	pat7: PKKKHTG (5) at 821
	bipartite: RKGLGEGVPSSQRGPRR at 231
	content of basic residues: 9.0%
	NLS Score: 2.86
	KDEL: ER retention motif in the C-terminus: none
	ER Membrane Retention Signals: none
	SKL: peroxisomal targeting signal in the C-terminus: none
	PTS2: 2nd peroxisomal targeting signal: none
	VAC: possible vacuolar targeting motif: none
	RNA-binding motif: none
	Actinin-type actin-binding motif:
	type 1: none
	type 2: none
	NMYR: N-myristoylation pattern: none
	Prenylation motif: none
	memYQRL: transport motif from cell surface to Golgi: none
	Tyrosines in the tail: none
	Dileucine motif in the tail: none
	checking 63 PROSITE DNA binding motifs: none
	checking 71 PROSITE ribosomal protein motifs: none
	checking 33 PROSITE prokaryotic DNA binding motifs: none
	NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination
	Prediction: nuclear
	Reliability: 89
	COIL: Lupas's algorithm to detect coiled-coil regions
	total: 0 residues
Final Results (k = 9/23):
39.1%: mitochondrial
34.8%: nuclear
17.4%: endoplasmic reticulum
4.3%: cytoplasmic
4.3%: peroxisomal
>> prediction for CG160244-01 is mit (k = 23)

[0426] A search of the NOV11a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 11C.

TABLE 11C
Geneseq Results for NOV11a
		NOV11a	Identities/
Geneseq	Protein/Organism/Length	Residues/Match	Similarities for	Expect
Identifier	[Patent #, Date]	Residues	the Matched Region	Value
AAB41456	Human ORFX ORF1220	1..1243	1225/1243 (98%)	0.0
	polypeptide sequence SEQ	41..1275	1227/1243 (98%)
	ID NO:2440-Homo
	sapiens, 1306 aa.
	[WO200058473-A2,
	5 OCT. 2000]
AAB95514	Human protein sequence	445..1390	943/954 (98%)	0.0
	SEQ ID NO:18083-Homo	2..955	944/954 (98%)
	sapiens, 1081 aa.
	[EP1074617-A2,
	7 FEB. 2001]
AAE20837	Human gene 2 encoded	1..622	617/622 (99%)	0.0
	secreted protein fragment,	90..711	618/622 (99%)
	SEQ ID NO:99-Homo
	sapiens, 720 aa.
	[WO200218435-A1,
	7 MAR. 2002]
AAB56941	Human prostate cancer	976..1390	413/415 (99%)	0.0
	antigen protein sequence	76..490	413/415 (99%)
	SEQ ID NO:1519-Homo
	sapiens, 616 aa.
	[WO200055174-A1,
	21 SEP. 2000]
AAB43300	Human ORFX ORF3064	995..1390	392/404 (97%)	0.0
	polypeptide sequence SEQ	1..404	394/404 (97%)
	sapiens, 530 aa.
	[WO200058473-A2,
	5 OCT. 2000]

[0427] In a BLAST search of public sequence datbases, the NOV11a protein was found to have homology to the proteins shown in the BLASTP data in Table 11D.

TABLE 11D
Public BLASTP Results for NOV11a
Protein		NOV11a Residues/	Identities/
Accession		Match	Similarities for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
O94987	Hypothetical protein	1..1243	1222/1243 (98%)	0.0
	KIAA0913-Homo sapiens	41..1270	1224/1243 (98%)
	(Human), 1301 aa
	(fragment).
Q9H8F3	Hypothetical protein	445..1390	943/954 (98%)	0.0
	FLJ13680-Homo sapiens	2..955	944/954 (98%)
	(Human), 1081 aa.
Q9GKV3	Hypothetical 41.8 kDa	260..657	381/398 (95%)	0.0
	protein-Macaca fascicularis	1..393	385/398 (96%)
	(Crab eating macaque)
	(Cynomolgus monkey), 399
	aa.
Q9VWN8	CG32542 protein-	429..1119	341/732 (46%)	e−161
	Drosophila melanogaster	852..1526	435/732 (58%)
	(Fruit fly), 2030 aa.
Q9D789	2310021P13Rik protein-	1133..1390	254/258 (98%)	e−152
	Mus musculus (Mouse),	1..258	256/258 (98%)
	384 aa.

[0428] PFam analysis predicts that the NOV11a protein contains the domains shown in the Table 11E.

TABLE 11E
Domain Analysis of NOV11a
		Identities/
		Similarities
		for the
		Matched	Expect
Pfam Domain	NOV11a Match Region	Region	Value

Example 12

[0429] 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: 83            1682 bp
NOV12a,          AAAACAAGCCGGGTGGCTGAGCCAGGCTGTGCACGGAGTGCCTGACGGGCCCAACAGACCCATGCTG
CG160541-01
DNA Sequence     CATCCAGAGACCTCCCCTGGCCGGGGGCATCTCCTGGCTGTGCTCCTGGCCCTCCTTGGCACCGCCT
                 GGGCAGAGGTGTGGCCACCCCAGCTGCAGGAGCAGGCTCCGATGGCCGGAGCCCTGAACAGGAAGGA
                 GAGTTTCTTGCTCCTCTCCCTGCACAACCGCCTGCGCAGCTGGGTCCAGCCCCCTGCCGCTGACATG
                 CGGAGGCTGGACTGGAGTGACAGCCTGGCCCAACTCGCTCAAGCCAGGCCAGCCCTCTGTCGAATCC
                 CAACCCCGAGCCTGGCGTCCGGCCTGTGGCGCACCCTGCAAGTGGGCTGGAACATGCAGCTGCTGCC
                 CGCGGGCTTGGCGTCCTTTGTTGAAGTGGTCAGCCTATGGTTTGCACAGGGGCAGCGGTACAGCCAC
                 GCGGCAGGAGAGTGTGCTCGCAACGCCACCTGCACCCACTACACGCAGCTCGTGTGGGCCACCTCAA
                 GCCAGCTGGGCTGTGGGCGGCACCTGTGCTCTGCAGGCCAGACAGCGATAGAAGCCTTTGTCTGTGC
                 CTACTCCCCCGGAGGCAACTCGGAGGTCAACGCGAAGACAATCATCCCCTATAAGAAGGGTGCCTGG
                 TGTTCGCTCTGCACAGCCAGTGTCTCAGGCTGCTTCAAAGCCTGGGACCATGCAGGGGGCCTCTGTG
                 AGGTCCCCAGGAATCCTTGTCGCATGAGCTGCCAGAACCATGGACGTCTCAACATCAGCACCTGCCA
                 CTGCCACTGTCCCCCTGGCTACACCGGCAGATACTGCCAAGCCAAGGTGCATTTTCCCTTCCACACC
                 TGTGACCTGAGGATCGACGGAGACTGCTTCATCGTGTCTTCAGAGGCACACACCTATTACAGAGCCA
                 GGATGAAATGTCAGAGGAAAGGCGGGGTGCTGGCCCAGATCAAGAGCCAGAAAGTGCAGGACATCCT
                 CGCCTTCTATCTCGGCCGCCTGGAGACCACCAACGAGGTGATTGACAGTGACTTCGAGACCAGGAAC
                 TTCTGGATCGGGCTCACCTACAAGACCCCCAAGGACTCCTTCCGCTGCGCCACAGGGGAGCACCACG
                 CCTTCACCAGTTTTGCCTTTGGGCAGCCTGACAACCACGGGTTTGGCAACTGCGTGGAQCTGCAGGC
                 TTCAGCTGCCTTCAACTGGAACAACCAGCGCTGCAAAACCCGAAACCGTTACATCTGCCAGTTTGCC
                 CAGGAGCACATCTCCCGGTGGGGCCCAGGGTCCTGAGGCCTGACCACATGGCTCCCTCGCCTGCCCT
                 GGGAQCACCGGCTCTGCTTACCTGTCCGCCCACCTGTCTGGAACAAGGGCCACGTTAAGACCACATG
                 CCTCATGTCCAAAGAGGTCTCAGACCTTGCACAATGCCACAAGTTGGGCACAGAGAGGCAGGGAGGC
                 CAGTGAGGGCCAGGGAGTGAGTGTTAGAAGAAGCTGGGGCCCTTCGCCTGCTTTTCATTGGGAAGAT
                 GGGCTTCAATTAGATGGCAAAGGACAGGACACCGCCAGTGGTCCAAAAAGGCTGCTCTCTTCCACCT
                 GGCCCAGACCCTGTGGGGCAGCGGAGCTTCCCTGTGGCATGAACCCCACAGGGTATTAAATTATGAA
                 TCAGCTG
                 ORF Start: ATG at 62                    ORF Stop: TGA at 1307
                 SEQ ID NO: 84            415 aa         MW at 46138.0kD
NOV12a,          MLHPETSPGRGHLLAVLLALLGTAWAEVWPPQLQEQAPMAGALNRKESFLLLSLHNRLRSWVQPPAA
CG160541-01
Protein Sequence DMRRLDWSDSLAQLAQARAALCGIPTPSLASGLWRTLQVGWNMQLLPAGLASFVEVVSLWFAEGQRY
                 SHAAGECARNATCTHYTQLVWATSSQLGCGRHLCSAGQTAIEAPVCAYSPGGNWEVNGKTIIPYKKG
                 AWCSLCTASVSGCFKAWDHAGGLCEVPRNPCRMSCQNHGRLNISTCHCHCPPCYTGRYCQAKVHFPF
                 HTCDLRIDQDCFMVSSEADTYYRARMKCQRKGGVLAQIKSQKVQDILAFYLGRLETTNEVIDSDFET
                 RNFWIGLTYKTAKDSFRWATGEHQAFTSFAFGQPDNHGFGNCVELQASAAFNWNNQRCKTRNRYICQ
                 FAQEHISRWGPGS

[0430] Further analysis of the NOV12a protein yielded the following properties shown in Table 12B.

TABLE 12B
Protein Sequence Properties NOV12a
SignalP analysis:	Cleavage site between residues 27 and 28
PSORT II	PSG:	a new signal peptide prediction method
analysis:		N-region:	length 10;	pos. chg 1;	neg. chg 1
		H-region:	length 16;	peak value	10.35
		PSG score:	5.95
	GvH:	von Heijne's method for signal seq. recognition
		GvH score (threshold: −2.1): 6.65
		possible cleavage site: between 26 and 27
	>>> Seems to have a cleavable signal peptide (1 to 26)
	ALOM:	Klein et al's method for TM region allocation
		Init position for calculation: 27
		Tentative number of TMS(s) for the threshold 0.5: 1
		Number of TMS(s) for threshold 0.5: 0
		PERIPHERAL	Likelihood = 5.52 (at 167)
		ALOM score: −1.12 (number of TMSs: 0)
	MTOP:	Prediction of membrane topology (Hartmann et al.)
		Center position for calculation: 13
		Charge difference: −4.0 C(−2.0) − N(2.0)
		N >= C: N-terminal side will be inside
	MITDISC:	discrimination of mitochondrial targeting seq
		R content:	1	Hyd Moment (75):	5.31
		Hyd Moment (95):	1.68	G content:	3
		D/E content:	2	S/T content:	3
		Score: −7.29
	Gavel:	prediction of cleavage sites for mitochondrial preseq
		R-2 motif at 20 GRG|HL
	NUCDISC:	discrimination of nuclear localization signals
		pat4: none
		pat7: none
		bipartite: none
		content of basic residues: 9.4%
		NLS Score: −0.47
	KDEL:	ER retention motif in the C-terminus: none
	ER Membrane Retention Signals: none
	SKL:	peroxisomal targeting signal in the C-terminus: none
	PTS2:	2nd peroxisomal targeting signal: none
	VAC:	possible vacuolar targeting motif: none
	RNA-binding motif: none
	Actinin-type actin-binding motif:
		type 1: none
		type 2: none
	NMYR: N-myristoylation pattern: none
	Prenylation motif: none
	memYQRL:	transport motif from cell surface to Golgi: none
	Tyrosines in the tail: none
	Dileucine motif in the tail: none
	checking 63 PROSITE DNA binding motifs: none
	checking 71 PROSITE ribosomal protein motifs: none
	checking 33 PROSITE prokaryotic DNA binding motifs: none
	NNCN:	Reinhardt's method for Cytoplasmic/Nuclear discrimination
		Prediction: cytoplasmic
		Reliability: 76.7
	COIL:	Lupas's algorithm to detect coiled-coil regions
		total: 0 residues
	Final Results (k = 9/23)
	33.3%:	extracellular, including cell wall
	22.2%:	vacuolar
	22.2%:	mitochondrial
	22.2%:	endoplasmic reticulum
	>> prediction for CG160541-01 is exc (k = 9)

[0431] A search of the NOV12a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 12C.

TABLE 12C
Geneseq Results for NOV12a
		NOV12a	Identities/
Geneseq	Protein/Organism/Length	Residues/Match	Similarities for	Expect
Identifier	[Patent #, Date]	Residues	the Matched Region	Value
AAE21077	Human 1139 (TANGO-139)	1..415	413/446 (92%)	0.0
	protein-Homo sapiens, 446	1..446	413/446 (92%)
	aa. [US2002028508-A1,
	7 MAR. 2002]
AAB64994	Human secreted protein #2-	1..415	413/446 (92%)	0.0
	Homo sapiens, 446 aa.	1..446	413/446 (92%)
	[WO200075375-A1,
	14 DEC. 2000]
AAE06575	Human protein having	1..415	413/446 (92%)	0.0
	hydrophobic domain,	1..446	413/446 (92%)
	HP10760-Homo sapiens,
	446 aa. [WO200149728-A2,
	12 JUL. 2001]
AAY41266	Human 1139 protein-Homo	1..415	413/446 (92%)	0.0
	sapiens, 446 aa.	1..446	413/446 (92%)
	[WO9954343-A2,
	28 OCT. 1999]
AAM93326	Human polypeptide, SEQ ID	1..415	409/446 (91%)	0.0
	NO: 2851-Homo sapiens,	1..446	410/446 (91%)
	446 aa. [EP1130094-A2,
	5 SEP. 2001]

[0432] 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
Protein		NOV11a Residues/	Identities/
Accession		Match	Similarities for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
CAC51149	Sequence 25 from Patent	1..415	413/446 (92%)	0.0
	WO0149728-Homo sapiens	1..446	413/446 (92%)
	(Human), 446 aa.
Q8NCF0	Hypothetical protein	1..415	409/446 (91%)	0.0
	FLJ90292-Homo sapiens	1..446	410/446 (91%)
	(Human), 446 aa.
Q9BE36	Hypothetical 35.9 kDa	1..225	211/225 (93%)	e−126
	protein-Macaca fascicularis	1..225	213/225 (93%)
	(Crab eating macaque)
	(Cynomolgus monkey), 334
	aa.
Q96HH2	Hypothetical protein-Homo	341..415	72/75 (96%)	8e−39
	sapiens (Human), 156 aa	82..156	73/75 (97%)
	(fragment).
Q9ET66	Cysteine-rich protease	42..231	67/198 (33%)	3e−20
	inhibitor-Mus musculus	20..196	89/198 (44%)
	(Mouse), 489 aa.

[0433] PFam analysis predicts that the NOV12a protein contains the domains shown in the Table 12E.

TABLE 12E
Domain Analysis of NOV12a
		Identities/
		Similarities
	NOV12a	for the Matched	Expect
Pfam Domain	Match Region	Region	Value
SCP	52..83	17/44 (39%)	0.0011
		23/44 (52%)
SCP	118..191	26/86 (30%)	1.2e−10
		49/86 (57%)
EGF	225..260	15/47 (32%)	0.33
		26/47 (55%)
lectin_c	285..403	34/137 (25%)	1.3e−17
		84/137 (61%)

Example 13

[0434] 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: 85            823 bp
NOV13a,          CCGGGCTGTGGTCTAGCATAAAGCCGGAGCCCAGAAGAAGGGGCGGGGTATGCGAGAAGCCTCCCCA
CG161630-01
DNA Sequence     CCTGCCCCCGCAAGGCGGCATCTGCTGGTCCTGCTGCTGCTCCTCTCTACCCTGGTGATCCCCTCCA
                 CTGCAGCTCCTATCCATGATGCTGACGCCCAAGAGACCTCCTTGGGTCTCACAGGCCTCCAGAGCCT
                 ACTCCAAGGCTTCAGCCGACTTTTCCTGAAAGGTAACCTGCTTCGGGGCATAGACAGCTTATTCTCT
                 GCCCCCATCGACTTCCGGGGCCTCCCTCGGAACTACCACAAAGACGAGAACCAGGAGCACCAGCTCG
                 GGAACAACACCCTCTCCAGCCACCTCCAGATCGACAAGATGACCGACAACAAGACAGGAGAGGTGCT
                 GATCTCCGAGAATGTGGTGGCATCCATTCAACCAGCGGAGGGGAGCTTCGAGGGTGATTTGAAGGTA
                 CCCAGGATCGAGGAGAAGGAGGCCCTGGTACCCATCCACAAGGCCACGGACAGCTTCCACACAGAAC
                 TCCATCCCCGGGTGGCCTTCTGGATCATTAAGCTGCCACGGCGGAGGTCCCACCAGGATGCCCTGGA
                 CCGCCGCCACTGGCTCAGCGAGAAGCGACACCGCCTGCAGGCCATCCGGGATGGACTCCGCAAGCGG
                 ACCCACAAGGACGTCCTAGAAGAGGGGACCGAGAGCTCCTCCCACTCCAGGCTGTCCCCCCGAAAGA
                 CCCACTTACTGTACATCCTCAGGCCCTCTCGGCAGCTGTAGGGGTGGGGACCGGGGAGCACCTGCCT
                 GTAGCCCCCATCAGACCCT
                 ORF Start: ATG at 50                    ORF Stop: TAG at 776
                 SEQ ID NO: 86            242 aa         MW at 27036.5kD
NOV13a,          MGEASPPAPARRHLLVLLLLLSTLVIPSTAAPIHDADAQESSLGLTGLQSLLQGFSRLFLKGNLLRG
CG161630-01
Protein Sequence IDSLFSAPMDFRGLPGNYHKEENQEHQLGNNTLSSHLQIDKMTDNKTGEVLISENVVASIQPAEGSF
                 EGDLKVPRMEEKEALVPIQKATDSFHTELHPRVAFWIIKLPRRRSHQDALEGGHWLSEKRHRLQAIR
                 DGLRKGTHKDVLEEGTESSSHSRLSPRKTHLLYILRPSRQL
                 SEQ ID NO: 87            655 bp
NOV13b,          CTCGAGGCCAAAATTCQGCACGAGGCCGGGCTGTGGTCTAGCATAAAGGCGGAGCCCAGAAGAAGGG
CG161630-02
DNA Sequence     GCGGGGTATGGGAGAAQCCTCCCCACCTGCCCCCGCAAGGCGGCATCTGCTGGTCCTGCTGCTGCTC
                 CTCTCTACCCTGGTGATCCCCTCCGCTGCAGCTCCTATCCATGATGCTGACGCCCAAGAGAGCTCCT
                 TGGGTCTCACAGGCCTCCAGAGCCTACTCCAAGGCTTCACCCGACTTTTCCTGAAAGTACCCACGAT
                 GGAGGAGAAGGAGGCCCTGGTACCCATCCAGAAGGCCACGGACAGCTTCCACACAGAACTCCATCCC
                 CCGGTGGCCTTCTGGATCATTAAGCTGCCACGGCGGAGGTCCCACCAGGATCCCCTGGAGGGCAGCC
                 ACTCGCTCAGCGAGAAGCGACACCGCCTGCAGGCCATCCCGGATGGACTCCCCAACGGGACCCACAA
                 GGACGTCCTAGAAGAGGGGACCGAGAGCTCCTCCCACTCCAGGCTGTCCCCCCGAAAGACCCACTTA
                 CTGTACATCCTCAGGCCCTCTCGGCAGCTGTAGGGGTGGGGACCGGGGAGCACCTGCCTGTAGCCCC
                 CATCAGACCCTGCCCCAAGCACCATATGGAAATAAAGTTCTTTCTTACATCT
                 ORF Start: ATG at 75                    ORF Stop: TAG at 567
                 SEQ ID NO: 88            164 aa         MW at 18500.1kD
NOV13b,          MGEASPPAPARRHLLVLLLLLSTLVIPSAAAPIHDADAQESSLGLTGLQSLLQGFSRLFLKVPRMEE
CG161630-02
Protein Sequence KEALVPIQKATDSFHTELHPRVAFWIIKLPRRRSHQDALEGSHWLSEKRHRLQAIRDGLRKGTHKDV
                 LEEGTESSSHSRLSPRKTHLLYILRPSRQL

[0435] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 13B.

TABLE 13B
Comparison of NOV13a against NOV13b.
	NOV13a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV13b	138..142	104/105 (99%)
	60..164	104/105 (99%)

[0436] Further analysis of the NOV13a protein yielded the following properties shown in Table 13C.

TABLE 13C
Protein Sequence Properties NOV13a
SignalP analysis:	Cleavage site between residues 31 and 32
PSORT II analysis:	PSG:	a new signal peptide prediction method
		N-region:	length 11;	pos. chg 1;	neg. chg 1
		H-region:	length 0;	peak value	0.66
		PSG score:	−3.74
	GvH:	von Heijne's method for signal seq. recognition
		GvH score (threshold: −2.1): 6.42
		possible cleavage site: between 30 and 31
	>>>Seems to have no N-terminal signal peptide
	ALOM:	Klein et al's method for TM region allocation
		Init position for calculation: 1
		Tentative number of TMS(s) for the threshold 0.5: 1
		Number of TMS(s) for threshold 0.5: 1
		INTEGRAL	Likelihood = −7.22	Transmembrane 14-30
		PERIPHERAL	Likelihood = 7.16 (at 43)
		ALOM score: −7.22 (number of TMSs: 1)
	MTOP:	Prediction of membrane topology (Hartmann et al.)
		Center position for calculation: 21
		Charge difference: −5.0 C(−2.5) − N(2.5)
		N >= C: N-terminal side will be inside
	>>> membrane topology: type 2 (cytoplasmic tail 1 to 14)
	MITDISC:	discrimination of mitochondrial targeting seq
		R content:	2	Hyd Moment (75):	4.91
		Hyd Moment(95):	7.07	G content:	1
		D/E content:	2	S/T content:	5
		Score: −4.24
	Gavel:	prediction of cleavage sites for mitochondrial preseq
		R-2 motif at 22 RRH|LL
	NUCDISC:	discrimination of nuclear localization signals
		pat4: PRRR (4) at 175
		pat4: KRHR (3) at 193
		pat7: PRRRSHQ (5) at 175
		bipartite: none
		content of basic residues: 12.4%
		NLS Score: 0.40
	KDEL:	ER retention motif in the C-terminus: none
	ER Membrane Retention Signals: none
	SKL:	peroxisomal targeting signal in the C-terminus: none
	PTS2:	2nd peroxisomal targeting signal: found
		RLSPRKTHL at 224
	VAC:	possible vacuolar targeting motif: none
	RNA-binding motif: none
	Actinin-type actin-binding motif:
		type 1: none
		type 2: none
	NMYR:	N-myristoylation pattern: none
	Prenylation motif: none
	memYQRL:	transport motif from cell surface to Golgi: none
	Tyrosines in the tail: none
	Dileucine motif in the tail: none
	checking 63 PROSITE DNA binding motifs: none
	checking 71 PROSITE ribosomal protein motifs: none
	checking 33 PROSITE prokaryotic DNA binding motifs: none
	NNCN:	Reinhardt's method for Cytoplasmic/Nuclear discrimination
		Prediction: nuclear
		Reliability: 89
	COIL:	Lupas's algorithm to detect coiled-coil regions
		total: 0 residues
	Final Results (k = 9/23):
	43.5%:	nuclear
	21.7%:	mitochondrial
	13.0%:	cytoplasmic
	8.7%:	Golgi
	4.3%:	plasma membrane
	4.3%:	extracellular, including cell wall
	4.3%:	peroxisomal
	>> prediction for CG161630-01 is nuc (k = 23)

[0437] 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
		NOV11a	Identities/
Geneseq	Protein/Organism/Length	Residues/Match	Similarities for	Expect
Identifier	[Patent #, Date]	Residues	the Matched Region	Value
AAM24259	Human EST encoded	1..242	241/242 (99%)	e−136
	protein SEQ ID NO: 1784-	1..242	241/242 (99%)
	Homo sapiens, 242 aa.
	[WO200154477-A2,
	2 AUG. 2001]
AAU29184	Human PRO polypeptide	1..242	241/242 (99%)	e−136
		1..242	241/242 (99%)
	sapiens, 242 aa.
	[WO200168848-A2,
	20 SEP. 2001]
AAB08878	A human Dickkopf	1..242	241/242 (99%)	e−136
	(Dkk)-related protein	1..242	241/242 (99%)
	designated Soggy-Homo
	sapiens, 242 aa.
	[WO200052047-A2,
	8 SEP. 2000]
AAW73020	Human cysteine-rich	1..242	241/242 (99%)	e−136
	secreted protein-like-	1..242	241/242 (99%)
	N-Homo sapiens, 242 aa.
	[WO9846755-A1,
	22 OCT. 1998]
AAY36062	Extended human secreted	1..242	232/242 (95%)	e−131
	protein sequence, SEQ ID	1..242	232/242 (95%)
	NO. 447-Homo sapiens,
	242 aa. [WO9931236-A2,
	24 JUN. 1999]

[0438] In a BLAST search of public sequence datbases, the NOV13a protein was found to have homology to the proteins shown in the BLASTP data in Table 13E.

TABLE 13E
Public BLASTP Results for NOV13a
		NOV13a	Identities/
Protein		Residues/	Similarities for
Accession	Protein/Organism/	Match	the Matched	Expect
Number	Length	Residues	Portion	Value
Q9UK85	Soggy-1 protein precursor	1..242	241/242 (99%)	e−136
	(SGY-1)-Homo sapiens	1..242	241/242 (99%)
	(Human), 242 aa.
CAC50177	Sequence 25 from Patent	12..229	167/218 (76%)	2e−87
	WO0146231-Homo sapiens	2..213	182/218 (82%)
	(Human), 312 aa.
Q9EQT4	Soggy-Mus musculus	14..242	148/230 (64%)	3e−78
	(Mouse), 230 aa.	4..230	181/230 (78%)
Q9ERW1	Soggy precursor (Soggy 1)-	14..242	147/230 (63%)	1e−77
	Mus musculus (Mouse), 230	4..230	179/230 (76%)
	aa.
Q9QZL9	Soggy-1 protein precursor	14..242	146/230 (63%)	9e−77
	(SGY-1)-Mus musculus	4..230	178/230 (76%)
	(Mouse), 230 aa.

[0439] PFam analysis predicts that the NOV13a protein contains the domains shown in the Table 13F.

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

Example 14

[0440] The NOV14 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 14A.

TABLE14A
NOV14 Sequence Analysis
                 SEQ ID NO: 89            1239 bp
NOV14a,          CAGACGGTACACCCCCGTCAGGTTCTTCCTCTGGCCCAGACCCTTGCGCTTCAGGTTCACCTGCCAC
CG161793-01
DNA Sequence     ACCTCACGGTGAGTTCTCCTGGAAGAAGAACCTGATGCCAGCCATCTGTCAAGGAAGACAGGAAGTA
                 ACAGTGCAGGCTCAGTGTGCTCGGCCCCTTCATCTCTCAGCTGCAGCAATGGAATACGTGCTCGAAG
                 TGAACAACTCTCCGCGGCACCTCCTGAACCAATTCACAGTGTGTGACGTTCCTCTGTATGACATTTG
                 TGACTACAACGTCTCCACGGACCGATGCCAGGAGCTCGGGTGCTGCTTCTACGAAGGCGTCTGCTAC
                 AAGAAAGCGGTTCCCATTTACATCCACGTGTTCTCTGCCTTGATTQTCATCATCGCTGGGGCCTTCG
                 TCATCACCATCATCTACAGAGTCATTCAGGAGAGCAGGAAAGAAAAGGCCATCCCTGTGGATGTCGC
                 GCTGCCACAGAAGTCCAGCGAAAAGGCGCAGTTGGCCTCATCCAGCAGCAAGTTAGGGCTGAAGCCT
                 GCGAGTCCTGGGCCTCCAAGTGCTGGGCCCTCCATGAAGAGTGACGAGGATAAGGATGATGTAACAG
                 GGACAATAACAGAAGCCGAAGAAACTGACGACTGACTGACACGCATGAAGAAGTGGAGATTGTCAGA
                 ATTATCCAAATGAAATGGTACAGCAGGTGCACTGTTAACAGTGTGATGGAATGACCACCCAAAGAGA
                 AACAAACAATAAAGGGGTTATTTTTTGGAAAAATTCAAACAAAAAAAAAAAAAAAACAAAAAAAACA
                 ACAGAACCAAAAAAAAACAAAAAAAAAAAAAATTCAAACAAAAAAAAAAAAAAAAACAAAAAAAACA
                 CCCGGGAGGGGCGGCCCAAGTTTTTGGCGCCGCTCACCCCCGGTTTTGTTGGGACACAGAAGGGGGG
                 CCCCGGAGGGGCGGCCCAAGTTTTTGGCGCCGCTCACCCCCGGTTTTGTTGGGACACAGAAGGGCGG
                 CCCCCCTAATGACGGGCCCGCTTTATAATAAAACGCCCAGGCGACCGGGCCGCCCGTGTTTTAACAC
                 CCGGCGCTCCGAGCTGGGGAGAAACCCGGGCACCGGGGGGGGAACCCGTGGGGAGGGAGACCCTCAA
                 GACCGGGGGGGGGGAGGAACAATAGCGGCCACACCCCCCCCACGACAAATTAAAGCCCCCGAGGGCA
                 CAAAATTAAGATCTCACGGGCACAACGGCTCAACACCCAGCGCAAATTAGCCCGCGCGCCGAAAAGT
                 TTGCCCCACGGGGATAGTCTGACGACATTCTCG
                 ORF Start: ATG at 102                   ORF Stop: TGA at 636
                 SEQ ID NO: 90            178 aa         MW at 19481.1kD
NOV14a,          MPAICQGRQEVTVQAQCARPLHLSAAAMEYVLEVKNSPRHLLKQFTVCDVPLYDICDYNVSRDRCQE
CG161793-01
Protein Sequence LGCCFYEGVCYKKAVPIYIHVFSALIVIIAGAFVITIIYRVIQESRKEKAIPVDVALPQKSSEKAEL
                 ASSSSKLGLKPASPGPPSAGPSMKSDEDKDDVTGTITEAEETED

[0441] Further analysis of the NOV14a protein yielded the following properties shown in Table 14B.

TABLE 14B
Protein Sequence Properties NOV14a
SignalP analysis:	No Known Signal Sequence Predicted
PSORT II analysis:	PSG:	a new signal peptide prediction method
		N-region:	length 10;	pos. chg 1;	neg. chg 1
		H-region:	length 8;	peak value	1.78
		PSG score:	−2.62
	GvH:	von Heijne's method for signal seq. recognition
		GvH score (threshold: −2.1): −9.59
		possible cleavage site: between 27 and 28
	>>> Seems to have no N-terminal signal peptide
	ALOM:	Klein et al's method for TM region allocation
		Init position for calculation: 1
		Tentative number of TMS(s) for the threshold 0.5: 1
		Number of TMS(s) for threshold 0.5: 1
		INTEGRAL	Likelihood = −11.36	Transmembrane 89-105
		PERIPHERAL	Likelihood = 7.64 (at 68)
		ALOM score: −11.36 (number of TMSs: 1)
	MTOP:	Prediction of membrane topology (Hartmann et al.)
		Center position for calculation: 96
		Charge difference: −0.5 C(1.0) − N(1.5)
		N >= C: N-terminal side will be inside
	>>> membrane topology: type 2 (cytoplasmic tail 1 to 89)
	MITDISC:	discrimination of mitochondrial targeting seq
		R content:	2	Hyd Moment (75):	5.69
		Hyd Moment (95):	1.83	G content:	1
		D/E content:	2	S/T content:	2
		Score: −5.65
	Gavel:	prediction of cleavage sites for mitochondrial preseq
		R-2 motif at 29 ARP|LH
	NUCDISC:	discrimination of nuclear localization signals
		pat4: none
		pat7: none
		bipartite: none
		content of basic residues: 10.7%
		NLS Score: −0.47
	KDEL:	ER retention motif in the C-terminus: none
	ER Membrane Retention Signals: none
	SKL:	peroxisomal targeting signal in the C-terminus: none
	PTS2:	2nd peroxisomal targeting signal: none
	VAC:	possible vacuolar targeting motif: none
	RNA-binding motif: none
	Actinin-type actin-binding motif:
		type 1: none
		type 2: none
	NMYR:	N-myristoylation pattern: none
	Prenylation motif: none
	memYQRL:	transport motif from cell surface to Golgi: none
	Tyrosines in the tail: too long tail
	Dileucine motif in the tail: found
		LL at 41
	checking 63 PROSITE DNA binding motifs: none
	checking 71 PROSITE ribosomal protein motifs: none
	checking 33 PROSITE prokaryotic DNA binding motifs: none
	NNCN:	Reinhardt's method for Cytoplasmic/Nuclear discrimination
		Prediction: cytoplasmic
		Reliability: 55.5
	COIL:	Lupas's algorithm to detect coiled-coil regions
		total: 0 residues
	Final Results (k = 9/23):
	34.8%:	mitochondrial
	21.7%:	cytoplasmic
	17.4%:	Golgi
	8.7%:	endoplasmic reticulum
	4.3%:	vacuolar
	4.3%:	extracellular, including cell wall
	4.3%:	nuclear
	4.3%:	vesicles of secretory system
	>> prediction for CG161793-01 is mit (k = 23)

[0442] A search of the NOV14a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 14C.

TABLE 14C
Geneseq Results for NOV14a
	Protein/	NOV14a	Identities/
	Organism/Length	Residues/	Similarities for
Geneseq	[Patent #,	Match	the Matched	Expect
Identifier	Date]	Residues	Region	Value
ABB08204	Human lipid metabolism	104..165	17/62 (27%)	0.61
	enzyme-4 (LME-4)-Homo	458..519	33/62 (52%)
	sapiens, 1216 aa.
	[WO200185956-A2,
	15 NOV. 2001]
AAB94695	Human protein sequence SEQ	104..165	17/62 (27%)	0.61
	ID NO:15668-Homo	35..96	33/62 (52%)
	sapiens, 639 aa.
	[EP1074617-A2,
	7 FEB. 2001]
AAM80177	Human protein SEQ ID NO	104..165	17/62 (27%)	0.61
	3823-Homo sapiens, 1058	300..361	33/62 (52%)
	aa. [WO200157190-A2,
	9 AUG. 2001]
AAM79193	1855-Homo sapiens, 1216	458..519	33/62 (52%)	0.61
	aa. [WO200157190-A2,
	9 AUG. 2001]
AAB50134	Human brain T calcium	71..164	25/96 (26%)	0.80
	channel alpha 1G subunit	6..93	40/96 (41%)
	gene exon 33 protein-Homo
	sapiens, 118 aa.
	[WO200070044-A2,
	23 NOV. 2000]

[0443] In a BLAST search of public sequence datbases, the NOV14a protein was found to have homology to the proteins shown in the BLASTP data in Table 14D.

TABLE 14D
Public BLASTP Results for NOV14a
		NOV14a	Identities/
Protein		Residues/	Similarities for
Accession	Protein/Organism/	Match	the Matched	Expect
Number	Length	Residues	Portion	Value
Q8N6K0	Similar to evidence: NAS putative	28..178	151/151 (100%)	4e−83
	unclassifiable-Homo sapiens	1..151	151/151 (100%)
	(Human), 151 aa.
Q9DA77	1700018L24Rik protein-Mus	28..134	64/109 (58%)	9e−32
	musculus (Mouse), 186 aa.	1..109	80/109 (72%)
T46339	hypothetical protein	104..165	17/62 (27%)	1.8
	DKFZp434A0814.1-human, 913	198..259	33/62 (52%)
	aa (fragment).
A53430	1-phosphatidylinositol-4,5-bisphosphate	104.465	17/62 (27%)	1.8
	phosphodiesterase (EC	458..519	33/62 (52%)
	3.1.4.11) beta-1b-rat, 1173 aa.
BAA25507	KIAA0581 protein-Homo sapiens	104..165	17/62 (27%)	1.8
	(Human), 1076 aa (fragment).	318..379	33/62 (52%)

[0444] PFam analysis predicts that the NOV14a protein contains the domains shown in the Table 14E.

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

Example 15

[0445] 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: 91            947 bp
NOV15a,          GCCTACTTACAGAGAGGCCAACTCAGACACAGCCGTGTATGCTCCCAGCAGCAACGGAGGTTCAGCT
CG162177-01
DNA Sequence     CCGCCTGCAGGGACAGAAAGACATGGTCTGGAAATGGATGCCACTTCTGCTGCTTCTGGTCTGTGTA
                 GCCACCATGTGCAGTGCCCAGGACAGGACTGATCTCCTCAATGTCTGTATGGATGCCAAGCACCACA
                 AGACAAAGCCAGGTCCTGACGACAAGCTGCATGACCAATGCAGTCCCTCGAAGAAOAATGCCTGCTG
                 CACAGCCAGCACCAGCCAGGAGCTGCACAAGGACACCTCCCGCCTGTACAACTTTAACTGGGACCAC
                 TGCCGCAAGATGGAGCCCGCCTQCAAGCGCCACTTCATCCAGGACACCTGTCTCTATCAGTGCTCAC
                 CCAACCTGCGGCCCTGCATCCAGCAGGTGAATCAGAGCTGGCGCAAAGAACGCTTCCTGGATGTGCC
                 CTTATGCAAAGAGGACTGTCAGCGCTGGTGGGAGGATTGTCACACCTCCCACACGTGCAAGAGCAAC
                 TGGCACAGAGGATGGGACTGGACCTCAGGAGTTAACAAGTGCCCAGCTGGGGCTCTCTGCCGCACCT
                 TTGAGTCCTACTTCCCCACTCCAGCTGCCCTTTGTGAAGGCCTCTGGAGTCACTCATACAAGGTCAG
                 CAACTACAGCCGAGGGAGCGGCCGCTGCATCCAGATGTGGTTTGATTCAGCCCAGGGCAACCCCAAC
                 GAGGAAGTCGCGAGGTTCTATGCTGCAGCCATGCATGTGAATGCTGGTGAGATGCTTCATGGQACTG
                 GGGGTCTCCTGCTCAGTCTGGCCCTCATGCTGCAACTCTGGCTCCTTGGCTGAGTTCAGTCCTCCCA
                 GACTACCTGCCCTCAGCTTGOATAACCAGGCTGGQCTCAGCTCAGCTCCCACAAATGACAGCCCCTT
                 AAGCATGCT
                 ORF Start: ATG at 90                    ORF Stop: TGA at 855
                 SEQ ID NO: 92            255 aa         MW at 29279.2kD
NOV15a,          MVWKWMPLLLLLVCVATMCSAQDRTDLLNVCMDAKHHKTKPGPEDKLHDQCSPWKKNACCTASTSQE
CG162177-01
Protein Sequence LHKDTSRLYNFNWDHCGKMEPACKRHFIQDTCLYECSPNLGPWIQQVNQSWRKERFLDVPLCKEDCQ
                 RWWEDCHTSHTCKSNWHRGWDWTSGVNKCPAGALCRTFESYFPTPAALCEGLWSHSYKVSNYSRGSG
                 RCIQMWFDSAQGNPNEEVARFYAAAMHVNAGEMLHGTGGLLLSLALMLQLWLLG
                 SEQ ID NO: 93            814 bp
NOV15b,          GCCTACTTACAGAGAGGCCAACTCAGACACAGCCGTGTATGCTCCCAGCACCAACGGAAGGTTCAGC
CG162177-02
DNA Sequence     TCCGCCTGCAGGGACAGAAAGACATGGTCTGGAAATGGATGCCACTTCTGCTGCTTCTGGTCTGTGT
                 AGCCACCATGTGCAGTGCCCAGGACAGGACTGATCTCCTCAATGTCTGTATCGATGCCAAGCACCAC
                 AAGACAAAGCCACGTCCTGAGGACAAGCTGCATGACCAATGCAGTCCCTCGAAGAAGAATGCCTGCT
                 GCACAGCCAGCACCAGCCAGGAGCTGCACAAGGACACCTCCCGCCTGTACAACTTTAACTGGGACCA
                 CTGCGGCAAGATGGAGCCCGCCTGCAAGCGCCACTTCATCCAGGACACCTGTCTCTATGAGTGCTCA
                 CCCAACCTGCGGCCCTGGATCCAGCAGGTGAATCAGAGCTGGCGCAAAGAACGCTTCCTGGATGTGC
                 CCTTATGCAAAGAGGACTGTCAGCGCTGGTGGGAGGATTGTCACACCTCCCACACGTGCAAGAGCAA
                 CTGGCACAGAGGATGGGACTCGACCTCAGCTGCCCTTTGTGAAGGCCTCTGGAGTCACTCATACAAG
                 GTCAGCAACTACAGCCGAGGGAGCGGCCGCTGCATCCAGATGTGGTTTGATTCAGCCCAGCGCAACC
                 CCAACGAGGAAGTGGCGAGGTTCTATGCTGCAGCCATGCATGTGAATGCTGGTGAGATGCTTCATGG
                 GACTGGGGGTCTCCTGCTCAGTCTGGCCCTGATGCTGCAACTCTGGCTCCTTGGCTGAGTTCAGTCC
                 TCCCACACTA
                 ORF Start: ATG at 91                    ORF Stop: TGA at 793
                 SEQ ID NO: 94            234 aa         MW at 27038.7kD
NOV 15b,         MVWKWMPLLLLLVCVATMCSAQDRTDLLNVCMDAKHHKTKPGPEDKLHDQCSPWKKNACCTASTSQE
CG162177-02
Protein Sequence LHKDTSRLYNWDHCGKMEPACKRHFIQDTCLYECSPNLGPWIQQVNQSWRKERFLDVPLCKEDCQ
                 RWWEDCHTSHTCKSNWHRGWDWTSAALCEGLWSHSYKVSNYSRGSGRCIQMWFDSAQGNPNEEVARF
                 YAAAMHVNAGEMLHGTGGLLLSLALMLQLWLLG

[0446] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 15B.

TABLE 15B
Comparison of NOV15a against NOV15b.
	NOV15a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV15b	1..255	234/255 (91%)
	1..234	234/255 (91%)

[0447] Further analysis of the NOV15a protein yielded the following properties shown in Table 15C.

TABLE 15C
Protein Sequence Properties NOV15a
SignalP analysis:	Cleavage site between residues 22 and 23
PSORT II	PSG:	a new signal peptide prediction method
analysis:		N-region:	length 4;	pos. chg 1;	neg. chg 0
		H-region:	length 18;	peak value	11.09
		PSG score:	6.69
	GvH:	von Heijne's method for signal seq. recognition
		GvH score (threshold: −2.1): 5.18
		possible cleavage site: between 21 and 22
	>>> Seems to have a cleavable signal peptide (1 to 21)
	ALOM:	Klein et al's method for TM region allocation
		Init position for calculation: 22
		Tentative number of TMS(s) for the threshold 0.5: 1
		Number of TMS(s) for threshold 0.5: 1
		INTEGRAL	Likelihood = −2.44	Transmembrane 239-255
		PERIPHERAL	Likelihood = 8.22 (at 219)
		ALOM score: −2.44 (number of TMSs: 1)
	MTOP:	Prediction of membrane topology (Hartmann et al.)
		Center position for calculation: 10
		Charge difference: −2.0 C (0.0) − N(2.0)
		N >= C: N-terminal side will be inside
	>>> membrane topology: type 1a (cytoplasmic tail 255 to 255)
	>>> Seems to be GPI anchored
	MITDISC:	discrimination of mitochondrial targeting seq
		R content:	0	Hyd Moment (75):	7.26
		Hyd Moment (95):	6.46	G content:	0
		D/E content:	1	S/T content:	2
		Score: −4.19
	Gavel:	prediction of cleavage sites for mitochondrial preseq
		cleavage site motif not found
	NUCDISC:	discrimination of nuclear localization signals
		pat4: none
		pat7: none
		bipartite: none
		content of basic residues: 10.2%
		NLS Score: −0.47
	KDEL:	ER retention motif in the C-terminus: none
	ER Membrane Retention Signals: none
	SKL:	peroxisomal targeting signal in the C-terminus: none
	PTS2:	2nd peroxisomal targeting signal: none
	VAC:	possible vacuolar targeting motif: none
	RNA-binding motif: none
	Actinin-type actin-binding motif:
		type 1: none
		type 2: none
	NMYR:	N-myristoylation pattern: none
	Prenylation motif: none
	memYQRL:	transport motif from cell surface to Golgi: none
	Tyrosines in the tail: none
	Dileucine motif in the tail: none
	checking 63 PROSITE DNA binding motifs: none
	checking 71 PROSITE ribosomal protein motifs: none
	checking 33 PROSITE prokaryotic DNA binding motifs: none
	NNCN:	Reinhardt's method for Cytoplasmic/Nuclear discrimination
		Prediction: cytoplasmic
		Reliability: 55.5
	COIL:	Lupas's algorithm to detect coiled-coil regions
		total: 0 residues
	Final Results (k = 9/23):
	55.6%:	extracellular, including cell wall
	22.2%:	endoplasmic reticulum
	11.1%:	Golgi
	11.1%:	plasma membrane
	>> prediction for CG162177-01 is exc (k = 9)

[0448] 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	Identities/
	Protein/Organism/	Residues/	Similarities for
Geneseq	length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAB50286	Human folate receptor II	1..255	254/255 (99%)	e−164
	protein SEQ ID NO:6-	1..255	255/255 (99%)
	Homo sapiens, 255 aa.
	30 NOV. 2000]
ABP41366	Human ovarian antigen	8..254	187/252 (74%)	e−115
	HLHCI46, SEQ ID NO:2498-	22..269	207/252 (81%)
	Homo sapiens, 270 aa.
	[WO200200677-A1,
	3 JAN. 2002]
ABG19167	Novel human diagnostic	1..231	183/238 (76%)	e-112
	protein #19158-Homo	3..240	203/238 (84%)
	sapiens, 248 aa.
	[WO200175067-A2,
	11 OCT. 2001]
ABG04155	Novel human diagnostic	50..254	141/209 (67%)	7e-81
	protein #4146-Homo	1..205	157/209 (74%)
	sapiens, 206 aa.
	[WO200175067-A2,
	11 OCT. 2001]
AAE09454	Human sbg72825FOLATEa	5..226	131/229 (57%)	2e-80
	protein-Homo sapiens, 250	4..229	158/229 (68%)
	aa. [WO200160850-A1,
	23 AUG. 2001]

[0449] 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	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
P14207	Folate receptor beta precursor	1..255	254/255 (99%)	e−164
	(FR-beta) (Folate receptor 2)	1..255	255/255 (99%)
	(Folate receptor,
	fetal/placental) (Placental
	folate-binding protein) (FBP)-
	Homo sapiens (Human), 255
	aa.
P41439	Folate receptor gamma	1..231	194/235 (82%)	e−125
	precursor (FR-gamma) (Folate	1..235	213/235 (90%)
	receptor 3)-Homo sapiens
	(Human), 243 aa.
Q05685	Folate receptor beta precursor	1..255	196/255 (76%)	e−121
	(FR-beta) (Folate receptor 2)	1..251	215/255 (83%)
	(Folate-binding protein 2)-
	Mus musculus (Mouse), 251
	aa.
P79388	Folate binding protein-Sus	1..254	187/254 (73%)	e−120
	scrofa (Pig), 253 aa.	1..252	214/254 (83%)
Q9R0D3	Folate receptor alpha-	6..253	188/251 (74%)	e−117
	Cricetulus griseus (Chinese	7..253	210/251 (82%)
	hamster), 261 aa.

[0450] PFam analysis predicts that the NOV15a protein contains the domains shown in the Table 15F.

TABLE 15F
Domain Analysis of NOV15a
	NOV15a	Identities/
	Match	Similarities	Expect
Pfam Domain	Region	for the Matched Region	Value
Folate_rec	5..246	182/247 (74%)	6.3e−174
		230/247 (93%)

EXAMPLE 16

[0451] 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: 95            1217 bp
NOV16a,          TTATGGCAGCCGGAACAGCAGTTGGAGCCTGGGTGCTGGTCCTCAGTCTGTGGGGCGCAGTAGTACG
CG162443-02
DNA Sequence     TGCTCAAAACATCACAGCTCGGATTGGCGAGCCACTGGTGCTGAAGTGTAACGGCGCCCCCAAGAAA
                 CCACCCCAGCGGCTGGAATCGAAACTGAACACAGGCCGGACAGAAGCTTCGAAGGTCCTGTCTCCCC
                 AGGGAGGAGGCCCCTGGGACAGTGTGGCTCGTGTCCTTCCCAACGGCTCCCTCTTCCTTCCGCCTGT
                 CGGGATCCAGGATGAGGGGATTTTCCGGTGCCAGGCAATGAACAGGAATGGAAAGGAGACCAAGTCC
                 AACTACCGAGTCCGTGTCTACCAGATTCCTGGGAAGCCAGAAATTGTAGATTCTGCCTCTGAACTCA
                 CGGCTGGTGTTCCCAATAAGGTGGGGACATGTGTGTCAGAGGGAAGCTACCCTGCAGGGACTCTTAG
                 CTGGCACTTGGATGCGAAGCCCCTGGTGCCTAATGAGAAGGGAGTATCTGTGAAGGAACAGACCAGG
                 AGACACCCTGAGACAGGGCTCTTCACACTGCAGTCGGAGCTAATGGTGACCCCAGCCCGGGGAGCAG
                 ATCCCCGTCCCACCTTCTCCTGTAGCTTCAGCCCAGGCCTTCCCCGACACCGGGCCTTGCGCACAGC
                 CCCCATCCAGCCCCGTGTCTGGGAGCCTGTGCCTCTGGAGGAGCTCCAATTGGTGGTGGACCCAGAA
                 GGTGGAGCAGTAGCTCCTGGTGGAACCGTAACCCTGACCTGTGAAGTCCCTGCCCAGCCCTCTCCTC
                 AAATCCACTGGATGAAGGATGGTGTQCCCTTGCCCCTTCCCCCCAGCCCTGTGCTGATCCTCCCTGA
                 GATAGGGCCTCAGGACCAGGGAACCTACAGCTGTGTGGCCACCCATTCCAGCCACGGGCCCCAGCAA
                 AGCCGTGCTGTCAGCATCAGCATCATCGAACCAGGCGACGAGGGGCCAACTGCAGGCTCTGTGGGAG
                 GATCAGGGCTGCGAACTCTAGCCCTGGCCCTGGGGATCCTGGGAGGCCTGGGGACAGCCGCCCTGCT
                 CATTGGGGTCATCTTGTGGCAAAGGCCGCAACGCCGAGGAGAGGAGACGAAGGCCCCAGAAAACCAG
                 GAGGAAGAGGACGAGCGTGCAGAACTGAATCAGTCGGAGGAACCTGAGGCAGGCGACAGTAGTACTG
                 GAGGGCCTTGA
                 ORF Start: ATG at 3                     ORF Stop: TGA at 1215
                 SEQ ID NO: 96            404 aa         MW at 42802.3kD
NOV16a,          MAAGTAVGAWVLVLSLWGAVVGAQNITARIGEPLVLKCKGAPKKPPQRLEWKLNTGRTEAWKVLSPQ
CG162443-02
Protein Sequence GGGPWDSVARVLPNGSLFLPAVGIQDEGIFRCQAMNRNGKETKSNYRVRVYQIPGKPEIVDSASELT
                 AGVPNKVGTCVSEGSYPAGTLSWHLDGKPLVPNEKGVSVKEQTRRHPETGLFTLQSELMVTPARGGD
                 PRPTFSCSFSPGLPRHRALRTAPIQPRVWEPVPLEEVQLVVEPEGGAVAPGGTVTLTCEVPAQPSPQ
                 IHWMKDGVPLPLPPSPVLILPEIGPQDQGTYSCVATHSSHGPQESRAVSISIIEPGEEGPTAGSVGG
                 SGLGTLALALGILGGLGTAALLIGVILWQRRQRRGEERKAPENQEEEEERAELNQSEEPEAGESSTG
                 GP
                 SEQ ID NO: 97            1226 bp
NOV16b,          GCCAGGACCCTGGAAGGAAGCAGGATGGCAGCCGGAACAGCAGTTGGAACCTGGGTGCTGGTCCTCA
CG162443-01
DNA Sequence     GTCTGTGGGGGGCAGTAGTAGGTGCTCAAAACATCACAGCCCGGATTGGCGAGCCACTGGTGCTGAA
                 GTGTAACGOGGCCCCCAAGAAACCACCCCAGCGGCTCGAATCGAAACTGGGAGGAGGCCCCTGGGAC
                 AGTGTGGCTCGTGTCCTTCCCAACGGCTCCCTCTTCCTTCCGGCTGTCGGCATCCAGGATGAGGGGA
                 TTTTCCGGTGCCAGGCAATGAACAGGAATGGAAAGGAGACCAAGTCCAACTACCGAGTCCGTGTCTA
                 CCAGATTCCTGCGAAGCCAGAAATTGTACATTCTGCCTCTGAACTCACGGCTGGTGTTCCCAATAAC
                 GTGCGGACATGTGTGTCAGAGGGAAGCTACCCTGCAGGGACTCTTAGCTGGCACTTGGATGGGAAGC
                 CCCTGGTGCCTAATGAGAAGGGAGTATCTGTGAAGGAACAGACCAGGAGACACCCTGAGACAGGGCT
                 CTTCACACTGCAGTCGGAGCTAATGGTGACCCCAGCCCGGGGAGGAGATCCCCGTCCCACCTTCTCC
                 TGTAGCTTCAGCCCAGGCCTTCCCCGACACCGGGCCTTGCGCACAGCCCCCATCCAGCCCCGTGTCT
                 GGGAGCCTGTGCCTCTGGAGGAGGTCCAATTGGTGGTGGAGCCAGAAGGTGGAGCAGTAGCTCCTGG
                 TGGAACCGTAACCCTGACCTGTGAAGTCCCTGCCCAGCCCTCTCCTCAAATCCACTGGATGAAGGAT
                 GGTGTGCCCTTGCCCCTTCCCCCCAGCCCTGTGCTGATCCTCCCTGAGATAGGCCCTCAGGACCAGG
                 GAACCTACAGCTGTGTGOCCACCCATTCCAGCCACGGGCCCCAGGAAAGCCGTGCTGTCAGCATCAG
                 CATCATCGAACCAGGCGAGGAGGGGCCAACTGCAGGCTCTGTGGGAGCATCAGGGCTCGGAACTCTA
                 GCCCTGGCCCTGGGGATCCTGGGAGGCCTGGCGACAGCCGCCCTGCTCATTGGGGTCATCTTGTGGC
                 AAAGGCCGCAACGCCGAGGAGAGGAGACGAAGGCCCCAGAAAACCAGGAGGAAGAGGAGGAGCGTGC
                 AGAACTGAATCAGTCGGAGGAACCTGAGGCAGGCGAGAGTAGTACTGGAGGGCCTTGAGGGGCCCAC
                 AGACAGATCCCATCCATCAG
                 ORF Start: ATG at 25                    ORF Stop: TGA at 1195
                 SEQ ID NO: 98            390 aa         MW at 41263.6kD
NOV16b,          MAAGTAVGTWVLVLSLWGAVVGAQNITARIGEPLVLKCKGAPKKPPQRLEWKLGGGPWDSVARVLPN
CG162443-01
Protein Sequence GSLFLPAVGIQDEGIFRCQAMNRNGKETKSNYRVRVYQIPGKPEIVDSASELTAGVPNKVGTCVSEG
                 SYPAGTLSWHLDGKPLVPNEKGVSVKEQTRRHPETGLFTLQSELMVTPARGGDPRPTFSCSFSPGLP
                 RHRALRTAPIQPRVWEPVPLEEVQLVVEPEGGAVAPGGTVTLTCEVPAQPSPQIHWMKDGVPLPLPP
                 SPVLILPEIGPQDQGTYSCVATHSSHGPQESRAVSISIIEPGEEGPTAGSVGGSGLGTLALALGILG
                 GLGTAALLIGVILWQRRQRRGEERKAPENQEEEEERAELNQSEEPEAGESSTGGP
                 SEQ ID NO: 99            1173 bp
NOV16c,          ATGGCAGCCGGAACAGCAGTTGGAGCCTGGGTGCTGGTCCTCAGTCTGTGGGGGGCAGTAGTAGGTG
CG162443-03
DNA Sequence     CTCAAAACATCACAGCCCGGATTGGCGAGCCACTGGTGCTGAAGTGTAAGGGGGCCCCCAAGAAACC
                 ACCCCAGCGGCTGGAATGGAAACTGGGAGGAGGCCCCTGGGACAGTGTGGCTCGTGTCCTTCCCAAC
                 GGCTCCCTCTTCCTTCCGGCTGTCGGGATCCAGGATGAGGGGATTTTCCGGTGCCAGGCAATGAACA
                 GGAATGGAAACGAGACCAAGTCCAACTACCGAGTCCGTGTCTACCAGATTCCTGGGAAGCCAGAAAT
                 TGTAGATTCTGCCTCTGAACTCACGGCTGGTGTTCCCAATAAGCTGGGGACATCTGTGTCAGAGGGA
                 AGCTACCCTGCAGGGACTCTTAGCTGGCACTTGGATGGGAAGCCCCTGGTGCCTAATGAGAAGGGAG
                 TATCTGTGAAGGAACAGACCAGGAGACACCCTGAGACAGGGCTCTTCACACTGCAGTCGGAGCTAAT
                 GGTGACCCCAGCCCGGGGAGGAGATCCCCGTCCCACCTTCTCCTGTAGCTTCAGCCCAGGCCTTCCC
                 CGACACCGGGCCTTGCGCACAGCCCCCATCCAGCCCCGTGTCTGGGAGCCTGTGCCTCTGGAGGAGG
                 TCCAATTGGTGGTGGAGCCAGAAGGTGGAGCAGTAGCTCCTGGTCGAACCGTAACCCTGACCTCTGA
                 AGTCCCTGCCCAGCCCTCTCCTCAAATCCACTGGATGAACGATGCTGTGCCCTTGCCCCTTCCCCCC
                 AGCCCTGTGCTGATCCTCCCTGAGATAGGGCCTCAGGACCAGGGAACCTACAGCTGTGTGGCCACCC
                 ATTCCAGCCACGGGCCCCAGGAAAGCCGTGCTGTCAGCATCAGCATCATCGAACCAGGCGAGGACGG
                 GCCAACTGCAGGCTCTGTGGGAGGATCAGGGCTGGGAACTCTAGCCCTGGCCCTGGGGATCCTGGGA
                 GGCCTGGGGACAGCCGCCCTGCTCATTGGGGTCATCTTGTGGCAAAGGCGGCAACCCCGAGGAGAGG
                 AGAGGAAGGCCCCAGAAAACCAGGAGGAAGAGGAGCAGCGTGCAGAACTGAATCAGTCGGAGGAACC
                 TGAGGCAGGCGAGAGTAGTACTGGAGGGCCTTGA
                 ORF Start: ATG at 1                     ORF Stop: TGA at 1171
                 SEQ ID NO: 100           390 aa         MW at 41233.5kD
NOV16c,          MAAGTAVGAWVLVLSLWGAVVGAQNITARIGEPLVLKCKGAPKKPPQRLEWKLGGGPWDSVARVLPN
CG162443-03
Protein Sequence GSLFLPAVGIQDEGIFRCQANNRNGKETKSNYRVRVYQIPGKPEIVDSASELTAGVPNKVGTCVSEG
                 SYPAGTLSWHLDGKPLVPNEKGVSVKEQTRRHPETGLFTLQSELMVTPARGGDPRPTFSCSFSPGLP
                 RHRALRTAPIQPRVWEPVPLEEVQLVVEPEGGAVAPGGTVTLTCEVPAQPSPQIHWMKDGVPLPLPP
                 SPVLILPEIGPQDQGTYSCVATHSSHGPQESRAVSISIIEPGEEGPTAGSVGGSGLGTLALALGILG
                 GLGTAALLIGVILWQRRQRRGEERKAPENQEEEEERAELNQSEEPEAGESSTGGP

[0452] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 16B.

TABLE 16B
Comparison of NOV16a against NOV16b and NOV16c.
	Protein	NOV16a Residues/	Identities/Similarities
	Sequence	Match Residues	for the Matched Region
	NOV16b	1..404	389/404 (96%)
		1..390	389/404 (96%)
	NOV16c	1..404	390/404 (96%)
		1..390	390/404 (96%)

[0453] Further analysis of the NOV16a protein yielded the following properties shown in Table 16C.

TABLE 16C
Protein Sequence Properties NOV16a
SignalP
analysis:	Cleavage site between residues 24 and 25
PSORT II	PSG:	a new signal peptide prediction method
analysis:		N-region:	length 0;	pos. chg 0;	neg. chg 0
		H-region:	length 28;	peak value	9.40
		PSG score:	5.00
	GvH:	von Heijne's method for signal seq. recognition
		GvH score (threshold: −2.1): 2.36
		possible cleavage site: between 22 and 23
	>>> Seems to have a cleavable signal peptide (1 to 22)
	ALOM:	Klein et al's method for TM region allocation
		Init position for calculation: 23
		Tentative number of TMS(s) for the threshold 0.5: 1
		Number of TMS(s) for threshold 0.5: 1
		INTEGRAL	Likelihood = −5.68	Transmembrane 345-361
		PERIPHERAL	Likelihood = 2.54 (at 75)
		ALOM score:	−5.68 (number of TMSs: 1)
	MTOP:	Prediction of membrane topology (Hartmann et al.)
		Center position for calculation: 11
		Charge difference: 2.0 C (3.0) − N(1.0)
		C > N: C-terminal side will be inside
	>>> Caution: Inconsistent mtop result with signal peptide
	>>> membrane topology: type 1a (cytoplasmic tail 362 to 404)
	MITDISC:	discrimination of mitochondrial targeting seq
		R content:	1	Hyd Moment (75):	2.53
		Hyd Moment (95):	0.37	G content:	5
		D/E content:	1	S/T content:	3
		Score: −6.73
	Gavel:	prediction of cleavage sites for mitochondrial preseq
		R-2 motif at 58 QRL|EW
	NUCDISC:	discrimination of nuclear localization signals
		pat4: none
		pat7: none
		bipartite: none
		content of basic residues: 9.4%
		NLS Score: −0.47
	KDEL:	ER retention motif in the C-terminus: none
	ER Membrane Retention Signals: none
	SKL:	peroxisomal targeting signal in the C-terminus: none
	PTS2:	2nd peroxisomal targeting signal: none
	VAC:	possible vacuolar targeting motif: none
	RNA-binding motif: none
	Actinin-type actin-binding motif:
		type 1: none
		type 2: none
	NMYR:	N-myristoylation pattern: none
	Prenylation motif: none
	memYQRL:	transport motif from cell surface to Golgi: none
	Tyrosines in the tail: none
	Dileucine motif in the tail: none
	checking 63 PROSITE DNA binding motifs: none
	checking 71 PROSITE ribosomal protein motifs: none
	checking 33 PROSITE prokaryotic DNA binding motifs: none
	NNCN:	Reinhardt's method for Cytoplasmic/Nuclear discrimination
		Prediction: cytoplasmic
		Reliability: 76.7
	COIL:	Lupas's algorithm to detect coiled-coil regions
		total: 0 residues
	Final Results (k = 9/23):
	44.4%:	endoplasmic reticulum
	22.2%:	Golgi
	22.2%:	extracellular, including cell wall
	11.1%:	plasma membrane
	>> prediction for CG162443-02 is end (k = 9)

[0454] 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 16D.

TABLE 16D
Geneseq Results for NOV16a
		NOV16a
		Residues/	Identities/
Geneseq	Protein/Organism/Length	Match	Similarities for the	Expect
Identifier	[Patent #, Date]	Residues	Matched Region	Value
AAB81925	Extracorporeal circulation	1..404	404/404 (100%)	0.0
	material receptor protein-	1..404	404/404 (100%)
	Unidentified, 404 aa.
	[WO200118060-A1,
	15 MAR. 2001]
AAM48745	Human RAGE protein SEQ	2..404	403/403 (100%)	0.0
	ID NO 1-Homo sapiens,	2..404	403/403 (100%)
	404 aa. [WO200192892-A2,
	6 DEC. 2001]
AAE23219	Human receptor for	2..404	402/403 (99%)	0.0
	advanced glycosylation end	2..404	403/403 (99%)
	product (RAGE) protein-
	Homo sapiens, 404 aa.
	[WO200230889-A2,
	18 APR. 2002]
AAU77543	Human receptor for	2..404	402/403 (99%)	0.0
	advanced glycosylation end	2..404	403/403 (99%)
	product (RAGE)-Homo
	sapiens, 404 aa.
	[WO200214519-A1,
	21 FEB. 2002]
AAW33753	Human RAGE polypeptide	1..340	340/340 (100%)	0.0
	(340 amino acid residues)-	1..340	340/340 (100%)
	Homo sapiens, 340 aa.
	[WO9739121-A1,
	23 OCT. 1997]

[0455] 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 16E.

TABLE 16E
Public BLASTP Results for NOV16a
		NOV16a
Protein		Residues/	Identities/
Accession		Match	Similarities for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
Q15109	Advanced glycosylation end	1..404	404/404 (100%)	0.0
	product-specific receptor	1..404	404/404 (100%)
	precursor (Receptor for
	advanced glycosylation end
	products)-Homo sapiens
	(Human), 404 aa.
Q28173	Advanced glycosylation end	1..404	337/417 (80%)	0.0
	product-specific receptor	1..416	363/417 (86%)
	precursor (Receptor for
	advanced glycosylation end
	products)-Bos taurus
	(Bovine), 416 aa.
Q62151	Advanced glycosylation end	1..404	315/404 (77%)	0.0
	product-specific receptor	1..403	341/404 (83%)
	precursor (Receptor for
	advanced glycosylation end
	products)-Mus musculus
	(Mouse), 403 aa.
Q63495	Advanced glycosylation end	1..404	315/404 (77%)	0.0
	product-specific receptor	1..402	345/404 (84%)
	precursor (Receptor for
	advanced glycosylation end
	products)-Rattus norvegicus
	(Rat), 402 aa.
O35444	RAGE-Mus musculus	1..404	316/404 (78%)	0.0
	(Mouse), 402 aa.	1..402	342/404 (84%)

[0456] PFam analysis predicts that the NOV16a protein contains the domains shown in the Table 16F.

TABLE 16F
Domain Analysis of NOV16a
			Identities/
		NOV16a	Similarities
	Pfam	Match	for the Matched	Expect
	Domain	Region	Region	Value
	ig	31..101	13/73 (18%)	0.00018
			44/73 (60%)
	ig	252..303	19/55 (35%)	5.1e−12
			39/55 (71%)

EXAMPLE 17

[0457] 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: 101           471 bp
NOV17a,          GGGACCGGGGCCATGTCTCCACACCTCACTGCTCTCCTGGGCCTAGTGCTCTGCCTGGCCCAGACCA
CG162509-02
DNA Sequence     TCCACACCCAGGAGGGGGCCCTTCCCAGACCCTCCATCTCGGCTGAGCCAGGCACTGTGATCTCCCC
                 GGGGAGCCATGTGACTTTCATGTGCCGGGGCCCGGTTGGGGTTCAAACATTCCGCCTGGAGAGGGAG
                 GATAGAGCCAAGTACAAAGATAGTTATAATGTGTTTCGACTTGGTCCATCTGAGTCAGAGGCCAGAT
                 TCCACATTGACTCAGTAAGTGAAGGAAATGCCGGGCTTTATCGCTGCCTCTATTATAAGCCCCCTGG
                 ATGGTCTGAGCACAGTGACTTCCTGGAGCTGCTGGTGAAAGAAAGCTCTGGAGGCCCGGACTCCCCG
                 GACACAGAGCCCGGCTCCTCAGCTGGGACTGTGCCAGGCACTGAAGCCTCCGGATTTGATGCACCAT
                 GA
                 ORF Start: ATG at 13                    ORF Stop: TGA at 469
                 SEQ ID NO: 102           152 aa         MW at 16279.9kD
NOV17a,          MSPHLTALLGLVLCLAQTIHTQEGALPRPSISAEPGTVISPGSHVTFMCRGPVGVQTFRLEREDRAK
CG162509-02
Protein Sequence YKDSYNVFRLGPSESEARFHIDSVSEGNAGLYRCLYYKPPGWSEHSDFLELLVKESSGGPDSPDTEP
                 GSSAGTVPGTEASGFDAP
                 SEQ ID NO: 103           478 bp
NOV17b,          CACCGGATCCACCATGTCTCCACACCTCACTGCTCTCCTGGGCCTAGTGCTCTGCCTGGCCCAGACC
306610228 DNA
Sequence         ATCCACACGCAGGAGGGGGCCCTTCCCAGACCCTCCATCTCGGCTGAGCCAGGCACTGTGATCTCCC
                 CGGGGAGCCATGTGACTTTCATGTGCCGGGGCCCGGTTGGGGTTCAAACATTCCGCCTGGAGAGGGA
                 GGATAGAGCCAAGTACAAAGATAGTTATAATGTGTTTCGACTTGGTCCATCTGAGTCAGAGGCCAGA
                 TTCCACATTGACTCAGTAAGTGAAGGAAATGCCGGGCTTTATCGCTGCCTCTATTATAAGCCCCCTG
                 GATGGTCTGAGCACAGTGACTTCCTGGAGCTGCTGGTGAAAGAAAGCTCTGGAGGCCCGGACTCCCC
                 GGACACAGAGCCCGGCTCCTCAGCTGGGACTGTGCCAGGCACTGAAGCCTCCGGATTTGATGCACCA
                 ORF Start: at 2                         ORF Stop: end of sequence
                 SEQ ID NO: 104           159 aa         MW at 16925.6kD
NOV17b,          TGSTMSPHLTALLGLVLCLAQTIHTQEGALPRPSISAEPGTVISPGSHVTFMCRGPVGVQTFRLERE
306610228
Protein Sequence DRAKYKDSYNVFRLGPSESEARFHIDSVSEGNAGLYRCLYYKPPGWSEHSDFLELLVKESSGGPDSP
                 DTEPGSSAGTVPGTEASGFDAPLEG
                 SEQ ID NO:105            427 bp
NOV17c,          CACCGGATCCACCATGTCTCCACACCTCACTGCTCTCCTGGGCCTAGTGCTCTGCCTGGCCCAGACC
306610270 DNA
Sequence         ATCCACACGCAGGAGGGGGCCCTTCCCAGACCCTCCATCTCGGCTGAGCCAGGCACTGTGATCTCCC
                 CGGGGAGCCATCTGACTTTCATGTGCCCGGGCCCGGTTGGGGTTCAAACATTCCGCCTGGAGAGGGA
                 GGATAGAGCCAAGTACAAAGATAGTTATAATGTGTTTCGACTTGGTCCATCTGAGTCAGAGGCCAGA
                 TTCCACATTGACTCAGTAAGTGAAGGAAATGCCGGGCTTTATCGCTGCCTCTATTATAAGCCCCCTG
                 GATGGTCTGAGCACAGTGACTTCCTGGAGCTGCTGGTGAAAGGGACTGTGCCAGGCACTGAAGCCTC
                 CGGATTTGATGCACCACTCGAGGGC
                 ORF Start: at 2                         ORF Stop: end of sequence
                 SEQ ID NO: 106           142 aa         MW at 15367.1kD
NOV17c,          TGSTMSPHLTALLGLVLCLAQTIHTQEGALPRPSISAEPGTVISPGSHVTFMCRGPVGVQTFRLERE
306610270
Protein Sequence DRAKYKDSYNVFRLGPSESEARFHIDSVSEGNAGLYRCLYYKPPGWSEHSDFLELLVKGTVPGTEAS
                 GFDAPLEG
                 SEQ ID NO: 107           421 bp
NOV17d,          GGGACCGGGGCCATGTCTCCACACCTCACTGCTCTCCTGGGCCTAGTGCTCTGCCTGGCCCAGACCA
CG162509-01
DNA Sequence     TCCACACGCAGGAGGGGGCCCTTCCCAGACCCTCCATCTCGGCTGAGCCAGGCACTGTGATCTCCCC
                 GGGGAGCCATGTGACTTTCATGTGCCGGGGCCCGGTTGGGGTTCAAACATTCCGCCTGGAGAGGGAG
                 GATAGAGCCAAGTACAAAGATAGTTATAATGTGTTTCGACTTGGTCCATCTGAGTCAGAGGCCAGAT
                 TCCACATTGACTCAGTAAGTGAAGGAAATGCCGGGCTTTATCGCTGCCTCTATTATAAGCCCCCTGG
                 ATGGTCTGAGCACAGTGACTTCCTGGAGCTGCTGGTGAAAGGGACTGTGCCAGGCACTGAAGCCTCC
                 GGATTTGATGCACCATGAA
                 ORE Start: ATG at 13                    ORF Stop: TGA at 418
                 SEQ ID NO: 108           135 aa         MW at 14721.5kD
NOV17d,          MSPHLTALLGLVLCLAGTIHTQEGALPRPSISAEPGTVISPGSHVTFMCRGPVGVQTFRLEREDRAK
CG162509-01
Protein Sequence YKDSYNVFRLGPSESEARFHIDSVSEGNAGLYRCLYYKPPGWSEHSDFLELLVKGTVPGTEASGFDA
                 P

[0458] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 17B.

TABLE 17B
Comparison of NOV17a against NOV17b through NOV17d.
	NOV17a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV17b	1..152	152/152 (100%)
	5..156	152/152 (100%)
NOV17c	1..152	135/152 (88%)
	5..139	135/152 (88%)
NOV17d	1..152	135/152 (88%)
	1..135	135/152 (88%)

[0459] Further analysis of the NOV17a protein yielded the following properties shown in Table 17C.

TABLE 17C
Protein Sequence Properties NOV17a
SignalP analysis:	Cleavage site between residues 22 and 23
PSORT II	PSG:	a new signal peptide prediction method
analysis:		N-region:	length 0;	pos. chg 0;	neg. chg 0
		H-region:	length 22;	peak value	10.25
		PSG score:	5.85
	GvH:	von Heijne's method for signal seq. recognition
		GvH score (threshold: −2.1): 2.05
		possible cleavage site: between 21 and 22
	>>> Seems to have a cleavable signal peptide (1 to 21)
	ALOM:	Klein et al's method for TM region allocation
		Init position for calculation: 22
		Tentative number of TMS(s) for the threshold 0.5: 0
		number of TMS(s) . . . fixed
		PERIPHERAL	Likelihood = 9.02 (at 38)
		ALOM score: 9.02 (number of TMSs: 0)
	MTOP:	Prediction of membrane topology (Hartmann et al.)
		Center position for calculation: 10
		Charge difference: −2.0 C(−0.5) − N(1.5)
		N >= C: N-terminal side will be inside
	MITDISC:	discrimination of mitochondrial targeting seq
		R content:	0	Hyd Moment(75):	3.32
		Hyd Moment (95):	2.96	G content:	1
		D/E content:	1	S/T content:	4
		Score: −5.02
	Gavel:	prediction of cleavage sites for mitochondrial preseq
		cleavage site motif not found
	NUCDISC:	discrimination of nuclear localization signals
		pat4: none
		pat7: none
		bipartite: none
		content of basic residues: 7.9%
		NLS Score: −0.47
	KDEL:	ER retention motif in the C-terminus: none
	ER Membrane Retention Signals: none
	SKL:	peroxisomal targeting signal in the C-terminus: none
	PTS2:	2nd peroxisomal targeting signal: none
	VAC:	possible vacuolar targeting motif: none
	RNA-binding motif: none
	Actinin-type actin-binding motif:
		type 1: none
		type 2: none
	NMYR:	N-myristoylation pattern: none
	Prenylation motif: none
	memYQRL:	transport motif from cell surface to Golgi: none
	Tyrosines in the tail: none
	Dileucine motif in the tail: none
	checking 63 PROSITE DNA binding motifs: none
	checking 71 PROSITE ribosomal protein motifs: none
	checking 33 PROSITE prokaryotic DNA binding motifs: none
	NNCN:	Reinhardt's method for Cytoplasmic/Nuclear discrimination
		Prediction: nuclear
		Reliability: 70.6
	COIL:	Lupas's algorithm to detect coiled-coil regions
		total: 0 residues
	Final Results (k = 9/23):
	66.7%:	extracellular, including cell wall
	22.2%:	mitochondrial
	11.1%:	nuclear
	>> prediction for CG162509-02 is exc (k = 9)

[0460] A search of the NOV17a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 17D.

TABLE 17D
Geneseq Results for NOV17a
		NOV17a
		Residues/	Identities/
Geneseq	Protein/Organism/Length	Match	Similarities for the	Expect
Identifier	[Patent #, Date]	Residues	Matched Region	Value
AAW62776	gamma and Fc alpha,	1..135	135/152 (88%)	7e−73
	designated DLAIR-2-Homo
	sapiens, 135 aa.
	[WO9824906-A2,
	11 JUN. 1998]
ABP41696	Human ovarian antigen	1..139	115/139 (82%)	2e−62
	HVVBV73, SEQ ID	36..174	123/139 (87%)
	NO:2828-Homo sapiens,
	322 aa. [WO200200677-A1,
	3 JAN. 2002]
AAB58453	Lung cancer associated	1..139	115/139 (82%)	2e−62
	polypeptide sequence SEQ	36..174	123/139 (87%)
	ID 791-Homo sapiens, 322
	aa. [WO200055180-A2,
	21 SEP. 2000]
AAW62775	Human receptor for Fc	1..139	115/139 (82%)	2e−62
	gamma and Fc alpha-Homo	1..139	123/139 (87%)
	sapiens, 287 aa.
	[WO9824906-A2,
	11 JUN. 1998]
AAW62774	Human receptor for Fc	1..139	115/139 (82%)	2e−62
	gamma and Fc alpha,	1..139	123/139 (87%)
	designated YE01-Homo
	sapiens, 287 aa.
	[WO9824906-A2,
	11 JUN. 1998]

[0461] In a BLAST search of public sequence datbases, the NOV17a protein was found to have homology to the proteins shown in the BLASTP data in Table 17E.

TABLE 17E
Public BLASTP Results for NOV17a
		NOV16a
Protein		Residues/	Identities/
Accession		Match	Similarities for	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
AAB69325	Leukocyte-associated Ig-like	1..152	135/152 (88%)	2e−72
	receptor-2- Homo sapiens	1..135	135/152 (88%)
	(Human), 135 aa.
AAB69324	Leukocyte-associated Ig-like	1..139	115/139 (82%)	7e−62
	receptor-1-Homo sapiens	1..139	123/139 (87%)
	(Human), 287 aa.
AAF71275	Leukocyte-associated Ig-like	1..139	115/139 (82%)	7e−62
	receptor 1D isoform-Homo	1..139	123/139 (87%)
	sapiens (Human), 209 aa.
AAF17107	Leukocyte-associated Ig-like	1..127	99/127 (77%)	4e−51
	receptor 1b-Homo sapiens	1..127	107/127 (83%)
	(Human), 270 aa.
AAF71274	Leukocyte-associated Ig-like	1..127	99/127 (77%)	5e−50
	receptor 1C isoform-Homo	1..126	107/127 (83%)
	sapiens (Human), 269 aa.

[0462] PFam analysis predicts that the NOV17a protein contains the domains shown in the Table 17F.

TABLE 17F
Domain Analysis of NOV17a
		Identities/Similarities
	NOV17a	for the Matched	Expect
Pfam Domain	Match Region	Region	Value
ig	42..103	11/66 (17%)	1.5e−05
		45/66 (68%)

EXAMPLE 18

[0463] 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: 109	800 bp
NOV18a,	CCCCTCTCCTGCCTGGACGGCTCTGCTGGTCTCCCCGTCCCCTGGAGAAGAACAAGGCCATGGGTCG
CG162645-02
DNA Sequence	GCCCCTGCTGCTGCCCCTACTGCCCCTGCTGCTGCCGCCAGCATTTCTGCAGCCTAGTGGCTCCACA
	GGATCTGGTCCAAGCTACCTTTATGGGGTCACTCAACCAAAACACCTCTCAGCCTCCATGGGTGGCT
	CTGTGGAAATCCCCTTCTCCTTCTATTACCCCTGGGAGTTAGCCACAGCTCCCGACGTGAGAATATC
	CTGGAGACGGGGCCACTTCCACGGGCAGTCCTTCTACAGCACAAGGCCGCCTTCCATTCACAAGGAT
	TATGTGAACCGGCTCTTTCTGAACTGGACAGAGGGTCAGAAGAGCGGCTTCCTCAGGATCTCCAACC
	TGCAGAAGCAGGACCAGTCTGTGTATTTCTGCCGAGTTGAGCTGGACACACGGAGCTCAGGGAGGCA
	GCAGTGGCAGTCCATCGAGGGGACCAAACTCTCCATCACCCAGGGTCAGCAGCGGACTAAAGCCACA
	ACCCCAGCCAGGGAACCCTTCCAAAACACAGAGGAGCCATATGAGAATATCAGGAATGAAGGACAAA
	ATACAGATCCCAAGCTAAATCCCAAGGATGACGGCATCGTCTATGCTTCCCTTGCCCTCTCCAGCTC
	CACCTCACCCAGAGCACCTCCCAGCCACCGTCCCCTCAAGAGCCCCCAGAACGAGAACCTGTACTCT
	GTCTTAAAGGCCTAACCAATGGACAGCCCTCTCAAAACTGAATGGTGAAAGGGCGATTCCAGC
	ORF Start: ATG at 60		ORF Stop: TAA at 750
	SEQ ID NO: 110	230 aa	MW at 25849.8 kD
NOV18a,	MGRPLLLPLLPLLLPPAFLQPSGSTGSGPSYLYGVTQPKHLSASMGGSVEIPFSFYYPWELATAPDV
CG162645-02
Protein Sequence	RISWRRGHFHGQSFYSTRPPSIHKDYVNRLFLNWTEGQKSGFLRISNLQKQDQSVYFCRVELDTRSS
	GRQQWQSIEGTKLSITQGQQRTKATTPAREPFQNTEEPYENIRNEGQNTDPKLNPKDDGIVYASLAL
	SSSTSPRAPPSHRPLKSPQNENLYSVLKA
	SEQ ID NO: 111	653 bp
NOV18b,	CTGGAGAAGAACAAGGCCATGGGTCGGCCCCTGCTGCTGCCCCTACTCCCCTGCTGCCGCCAG
CG162645-01
DNA Sequence	CGTTTCTGCAGCCTAGTGGCTCCACAGGATCTGGTCCAAGCTACCTTTATGGGGTCACTCAACCAAA
	ACACCTCTCAGCCTCCATGGGTGGCTCTGTGGAAATCCCCTTCTCCTTCTATTACCCCTGGGAGTTA
	GCCACTTCCATTCACAAGGATTATGTGAACCGGCTCTTTCTGAACTGGACAGAGGGTCAGAAGAGCG
	GCTTCCTCAGGATCTCCAACCTGCAGAAGCAGGACCAGTCTGTGTATTTCTGCCGAGTTGAGCTGGA
	CACACGGAGCTCAGGGAGGCAGCAGTGGCAGTCCATCGAGGGGACCAAACTCTCCATCACCCAGGGT
	CAGCAGCGGACTAAAGCCACAACCCCAGCCAGGGAACCCTTCCAAAACACAGAGGAGCCATATGAGA
	ATATCAGGAATGAAGGACAAAATACAGATCCCAAGCTAAATCCCAAGGATGACGGCATCGTCTATGC
	TTCCCTTGCCCTCTCCAGCTCCACCTCACCCAGAGCACCTCCCAGCCACCGTCCCCTCAAGAGCCCC
	CAGAACGAGAACCTGTACTCTGTCTTAAAGGCCTAACCAATGGACAGCCC
	ORF Start: ATG at 19		ORF Stop: TAA at 637
	SEQ ID NO: 112	206 aa	MW at 23012.7 kD
NOV18b,	MGRPLLLPLLPLLLPPAFLQPSGSTGSGPSYLYGVTQPKHLSASMGGSVEIPFSFYYPWELATSIHK
CG162645-01
Protein Sequence	DYVNRLFLNWTEGQKSGFLRISNLQKQDQSVYFCRVELDTRSSGRQQWQSIEGTKLSITQGQQRTKA
	TTPAREPFQNTEEPYENIRNEGQNTDPKLNPKDDGIVYASLALSSSTSPRAPPSHRPLKSPQNENLY
	SVLKA

[0464] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 18B.

TABLE 18B
Comparison of NOV18a against NOV18b.
	NOV18a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV18b	1..230	206/230 (89%)
	1..206	206/230 (89%)

[0465] Further analysis of the NOV18a protein yielded the following properties shown in Table 18C.

TABLE 18C
Protein Sequence Properties NOV18a
SignalP analysis:	Cleavage site between residues 20 and 21
PSORT II	PSG: a new signal peptide prediction method
analysis:		N-region:	length 3;	pos. chg 1;	neg. chg 0
		H-region:	length 35;	peak value	8.58
		PSG score:	4.18
	GvH:	von Heijne's method for signal seq. recognition
		GvH score (threshold: −2.1): 1.66
		possible cleavage site: between 19 and 20
	>>> Seems to have a cleavable signal peptide (1 to 19)
	ALOM:	Klein et al's method for TM region allocation
		Init position for calculation: 20
		Tentative number of TMS(s) for the threshold 0.5: 0
		number of TMS(s) . . . fixed
		PERIPHERAL	Likelihood = 8.91 (at 41)
		ALOM score: 8.91 (number of TMSs: 0)
	MTOP:	Prediction of membrane topology (Hartmann et al.)
		Center position for calculation: 9
		Charge difference: −1.5 C (0.5) − N(2.0)
		N >= C: N-terminal side will be inside
	MITDISC:	discrimination of mitochondrial targeting seq
		R content:	1	Hyd Moment (75):	10.02
		Hyd Moment (95):	8.02	G content:	7
		D/E content:	1	S/T content:	9
		Score: −3.94
	Gavel:	prediction of cleavage sites for mitochondrial preseq
		R-2 motif at 13 GRP|LL
	NUCDISC:	discrimination of nuclear localization signals
		pat4: none
		pat7: none
		bipartite: none
		content of basic residues: 10.9%
		NLS Score: −0.47
	KDEL:	ER retention motif in the C-terminus: none
	ER Membrane Retention Signals:
		XXRR-like motif in the N-terminus: GRPL
		KKXX-like motif in the C-terminus: SVLK
	SKL:	peroxisomal targeting signal in the C-terminus: none
	PTS2:	2nd peroxisomal targeting signal: none
	VAC:	possible vacuolar targeting motif: none
	RNA-binding motif: none
	Actinin-type actin-binding motif:
		type 1: none
		type 2: none
	NMYR:	N-myristoylation pattern: none
	Prenylation motif: none
	memYQRL:	transport motif from cell surface to Golgi: none
	Tyrosines in the tail: none
	Dileucine motif in the tail: none
	checking 63 PROSITE DNA binding motifs: none
	checking 71 PROSITE ribosomal protein motifs: none
	checking 33 PROSITE prokaryotic DNA binding motifs: none
	NNCN:	Reinhardt's method for Cytoplasmic/Nuclear discrimination
		Prediction: nuclear
		Reliability: 94.1
	COIL:	Lupas's algorithm to detect coiled-coil regions
		total: 0 residues
	Final Results (k = 9/23)
	44.4%:	extracellular, including cell wall
	22.2%:	mitochondrial
	22.2%:	nuclear
	11.1%:	cytoplasmic
	>> prediction for CG162645-02 is exc (k = 9)

[0466] 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
		NOV18a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAB07444	A human monocyte-derived	1..230	229/230 (99%)	e−134
	protein FDF03DeltaTM-	1..230	229/230 (99%)
	Homo sapiens, 230 aa.
	[WO200040721-Al,
	13 JUL. 2000]
ABG21403	Novel human diagnostic	1..179	157/179 (87%)	3e−89
	protein #21394-Homo	357..535	161/179 (89%)
	sapiens, 1012 aa.
	[WO200175067-A2,
	11 OCT. 2001]
ABG16869	Novel human diagnostic	1..179	157/179 (87%)	3e−89
	protein #16860-Homo	357..535	161/179 (89%)
	sapiens, 1012 aa.
	[WO200175067-A2,
	11 OCT. 2001]
ABG02851	Novel human diagnostic	1..179	157/179 (87%)	3e−89
	protein #2842-Homo	357..535	161/179 (89%)
	sapiens, 1012 aa.
	[WO200175067-A2,
	11 OCT. 2001]
ABG00509	Novel human diagnostic	1..179	157/179 (87%)	3e−89
	protein #500-Homo sapiens,	357..535	161/179 (89%)
	1012 aa. [WO200175067-A2,
	11 OCT. 2001]

[0467] 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
		NOV18a	Identities/
Protein		Residues/	Similarities for
Accession	Protein/Organism/	Match	the Matched	Expect
Number	Length	Residues	Portion	Value
CAC01614	Cell surface receptor	1..230	229/230 (99%)	e−134
	FDF03-dtm precursor-	1..230	229/230 (99%)
	Homo sapiens (Human), 230
	aa.
Q8NHI1	Similar to paired	1..216	196/216 (90%)	e−113
	immunoglobulin-like receptor	1..212	202/216 (92%)
	alpha-Homo sapiens
	(Human), 226 aa.
CAC01615	Cell surface receptor	1..152	151/152 (99%)	1e−86
	FDF03-M14 precursor-	1..152	152/152 (99%)
	Homo sapiens (Human), 175
	aa.
CAC01613	Cell surface receptor FDF03	1..169	155/169 (91%)	1e−86
	precursor-Homo sapiens	1..164	156/169 (91%)
	(Human), 303 aa.
Q9UKJ1	Inhibitory receptor	1..169	155/169 (91%)	1e−86
	PILRalpha-Homo sapiens	1..164
	(Human), 303 aa.

[0468] PFam analysis predicts that the NOV18a protein contains the domains shown in the Table 18F.

TABLE 18F
Domain Analysis of NOV18a
		Identities/Similarities
	NOV18a	for the Matched	Expect
Pfam Domain	Match Region	Region	Value
ig	65..127	10/65 (15%)	0.077
		47/65 (72%)

Example 19

[0469] 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: 113	2203 bp
NOV19a,	CACCGGATCCACCATGCTGCTGCCGCGGTCGGTGTCATCGGAGCGGGCCCCTGGGGTGCCGGAGCCG
CG162687-02
DNA Sequence	GAGGAGCTGTGGGAGGCAGAGATGGAGCGGCTGCGCGGCTCTGGGACGCCCGTGCGTGGGCTGCCCT
ATGCCATGATGGACAAGCGCCTCATCTGGCAGCTGCGGGAGCCCGCGGGGGTGCAGACCTTGCGCTG
	GCAGCGGTGGCAGCGCCGGCGGCAGACGGTGGAAAGGCGCCTGCGGGAGGCAGCGCAGCGGCTGGCC
	CGGGGCCTTGGGCTCTGGGAGGGGGCGCTCTACGAGATCGGGGGCCTCTTCGGCACAGGAATTCGGT
	CCTACTTCACCTTCCTCCGCTTCCTGCTGCTACTCAACCTGCTGAGTCTGCTGCTCACCGCAAGCTT
	CGTGCTGCTGCCCCTGGTCTGGCTCCGCCCCCCTGACCCAGGCCCCACCCTGAACTTGACCCTCCAG
	TGCCCTGGTAGCCGCCAGTCCCCGCCTGGCGTTTTGAGGTTCCACAATCAACTTTGGCATGTTTTGA
	CTGGCAGGGCCTTCACCAACACCTATCTCTTCTACGGTGCGTACCGAGTGGGGCCGGAGAGCAGCTC
	CGTGTACAGCATCCGCCTGACCTACCTCCTCAGCCCGCTGGCCTGCCTGCTCCTCTGCTTCTGTGGG
	ACTCTGCGGCGGATGGTGAAGGGGCTGCCGCAGAAGACTCTGCTGGGTCAGGGCTATCAGGCGCCTC
	TCAGCGCCAAGGTCTTCTCCTCATGGGACTTCTGCATCCGGGTGCAGGAAGCAGCCACCATCAAGAA
	GCATGAGATCAGCAACGAGTTCAAGGTGGAGCTGGAGGAGGGCCGTCGCTTCCAGCTGATGCAGCAG
	CAGACCCGGGCCCAGACGGCCTGCCGCCTGCTCTCCTACCTGCGGGTCAACGTACTCATCGGGCTCC
	TGGTGGTTGGGGCCATCAGCGCCATCTTCTGGGCTACCAAGTACTCACAGGACAACAAGGAGGAGTC
	CCTGTTTCTGCTGCTCCAGTACCTGCCCCCTGGGGTCATCGCCCTGGTCAACTTCCTGGGTCCCCTG
	CTGTTCACATTTCTGGTCCAGCTGGAGAACTACCCTCCCAACACGGAAGTCAACCTCACTCTGATCT
	GGTGCGTGGTGCTGAAGCTGGCCAGCTTGGGGATGTTCTCCGTCTCCCTGGGTCAGACCATACTGTG
	CATTGGCAGAGACAAGAGCAGCTGTGAGTCCTACGGCTACAACGTTTGTGACTATCAGTGCTGGGAG
	AACTCCGTGGGGGAGGAGCTGTACAAGCTGAGTATCTTCAACTTCCTCCTCACCGTGGCCTTCGCCT
	TCCTGGTCACCCTGCCTCGGAGGCTGCTGGTGGACCGGTTCTCAGGCCGGTTCTGGGCCTGGCTGGA
	ACGGGAGGAGTTCCTGGTCCCCAAGAATGTGCTGGACATCGTGGCGGGGCAGACGGTCACCTGGATG
	GGCCTCTTCTACTGCCCCCTGCTGCCCCTGCTGAATAGCGTCTTCCTCTTCCTCACCTTCTACATCA
	AGAAGTACACCCTCCTGAAGAACTCCAGGGCATCTTCGCGGCCCTTCCGTGCCTCCAGCTCCACCTT
	CTTCTTCCAGCTAGTGCTCCTCCTGGGCCTGCTTCTGGCTGCAGTGCCCCTGGGCTATGTGGTCAGC
	AGCATCCACTCCTCCTGGGACTACGGCCTCTTCACCAACTACTCAGCACCCTGGCAAGTGGTCCCGG
	AGCTGGTGGCCCTTGGGCTCCCGCCCATTGGCCAGCGTGCCCTCCACTACCTGGGCTCCCACGCCTT
	CAACTTCCCCCTCCTCATCATGCTCAGCCTTGTCCTGACGGTGTGCGTCTCCCAGACCCAGGCCAAT
	GCCAGGGCCATCCACAGGCTCCGGAAGCAGCTGGTGTGGCAGGTTCAGGAGAAGTGGCACCTGGTGG
	AGGACCTGTCGCGACTGCTGCCGGAGCCAGGCCCGAGCGACTCTCCGGGCCCCAAGTACCCTGCCTC
	CCAAGCTTCGCGCCCGCAGTCCTTCTGCCCCGGATGCCCATGCCCTGGCTCCCCGGGCCACCAGGCC
	CCGCCGCCCGGCCCCTCCGTCGTGGATGCCGCGGGACTGCGTTCCCCTTGCCCTGGACAGCACGGTG
	CCCCGGCCTCCGCCCGCAGATTCCGCTTCCCCAGCGGCGCGGAGCTGTAACTCGAGGGC
	ORF Start: ATG at 14		ORF Stop: TAA at 2192
	SEQ ID NO: 114	726 aa	MW at 81756.5 kD
NOV 19a,	MLLPRSVSSERAPGVPEPEELWEAEMERLRGSGTPVRGLPYAMMDKRLIWQLREPAGVQTLRWQRWQ
CG162687-02
Protein Sequence	RRRQTVERRLREAAQRLARGLGLWEGALYEIGGLFGTGIRSYFTFLRFLLLLNLLSLLLTASFVLLP
	LVWLRPPDPGPTLNLTLQCPGSRQSPPGVLRFHNQLWHVLTGRAFTNTYLFYGAYRVGPESSSVYSI
	RLTYLLSPLACLLLCFCGTLRRMVKGLPQKTLLGQGYQAPLSAKVFSSWDFCIRVQEAATIKKHEIS
	NEFKVELEEGRRFQLMQQQTRAQTACRLLSYLRVNVLIGLLVVGAISAIFWATKYSQDNKEESLFLL
	LQYLPPGVIALVNFLGPLLFTFLVQLENYPPNTEVNLTLIWCVVLKLASLGMFSVSLGQTILCIGRD
	KSSCESYGYNVCDYQCWENSVGEELYKLSIFNFLLTVAFAFLVTLPRRLLVDRFSGRFWAWLEREEF
	LVPKNVLDIVAGQTVTWMGLFYCPLLPLLNSVFLFLTFYIKKYTLLKNSRASSRPFRASSSTFFFQL
	VLLLGLLLAAVPLGYVVSSIHSSWDYGLFTNYSAPWQVVPELVALGLPPIGQRALHYLGSHAFNFPL
	LIMLSLVLTVCVSQTQANARAIHRLRKQLVWQVQEKWHLVEDLSRLLPEPGPSDSPGPKYPASQASR
	PQSFCPGCPCPGSPGHQAPRPGPSVVDAAGLRSPCPGQHGAPASARRFRFPSGAEL
	SEQ ID NO: 115	2629 bp
NOV19b,	CTGAGAAGGGGACTCCTCCAGGACTTGGTCCCTAGGTCCCCAGATGGGGAGACTGAGGCCGTGGCTG
CG162687-01
DNA Sequence	TGTGTCCCTCTGAGAGTTGGAGCGGGGCTGGGCCCGAATTCGACCCCAGCAGGATTCTCTCTCATTT
	CTGAGCCCCGGAGGTGGCAGAGCGGCAGACCCGGGCAAGTGAACCCTAGGGCTGCAGGAGCCCAGGC
	CCCGACGCCGGCGCAGAGGGGACGGAAGGGCCCGCCCCCAGCCCAGCGTGCACAGAGGCCATAGCCA
	AGGCCTTAAGGCTCATCCAACCGGGGACTCATATCCCCCCCACCGGCAGCCCGGCGCCCCAGCCTCT
	ACCCGTGCCCGCCGAGATGCTGCTGCCGCGGTCGGTGTCATCGGAGCGGGCCCCTGGGGTGCCGGAG
	CCGGAGGAGCTGTGGGAGGCAGAGATGGAGCGGCTGCGCGGCTCTGGGACGCCCGTGCGCGGGCTGC
	CCTATGCCATGATGGACAAGCGCCTCATCTGGCAGCTGCGGGAGCCCGCGGGGGTGCAGACCTTGCG
	CTGGCAGCGGTGGCAGCGCCGGCGGCAGACGGTGGAAAGGCGCCTGCGGGAGGCAGCGCAGCGGCTG
	GCCCGGGGCCTTGGGCTCTGGGAGGGGGCGCTCTACGAGATCGGGGGCCTCTTCGGCACAGGAATTC
	GGTCCTACTTCACCTTCCTCCGCTTCCTGCTGCTACTCAACCTGCTGAGCCTGCTGCTCACCGCAAG
	CTTCGTGCTGCTGCCCCTGGTCTGGCTCCGCCCCCCTGACCCAGGCCCCACCCTGAACTTGACCCTC
	CAGTGCCCTGGTAGCCGCCAGTCCCCGCCTGGCGTTTTGAGGTTCCACAATCAACTTTGGCATGTTT
	TGACTGGCAGGGCCTTCACCAACACCTATCTCTTCTACGGTGCGTACCGAGTGGGGCCGGAGAGCAG
	CTCCGTGTACAGCATCCGCCTGGCCTACCTCCTCAGCCCGCTGGCCTGCCTGCTCCTCTGCTTCTGT
	GGGACTCTGCGGCGGATGGTGAAGGGGCTGCCGCAGAAGACTCTGCTGGGTCAGGGCTATCAGGCGC
	CTCTCAGCGCCAAGGTCTTCTCCTCATGGGACTTCTGCATCCGGGTGCAGGAAGCAGCCACCATCAA
	GAAGCATGAGATCAGCAACGAGTTCAAGGTGGAGCTGGAGGAGGGCCGTCGCTTCCAGCTGATGCAG
	CAGCAGACCCGGGCCCAGACGGCCTGCCGCCTGCTCTCCTACCTGCGGGTCAACGTACTCAACGGGC
	TCCTGGTGGTTGGGGCCATCAGCGCCATCTTCTGGGCTACCAAGTACTCACAGGACAACAAGGAGGT
	GTCAGGCAACTGCATTCATTTAATCCTGGCCAGAACTGCGGGGGAGTCCCTGTTTCTGCTGCTCCAG
	TACCTGCCCCCTGGGGTCATCGCCCTGGTCAACTTCCTGGGTCCCCTGCTGTTCACATTTCTGGTCC
	AGCTGGAGAACTACCCTCCCAACACGGAGGTCAACCTCACTCTGATCTGGTGCGTGGTGCTGAAGCT
	GGCCAGCTTGGGGATGTTCTCCGTCTCCCTGGGTCAGACCATACTGTCCATTGGCAGAGACAAGAGC
	AGCTGTGAGTCCTACGGCTACAACGTTTGTGACTATCAGTGCTGGGAGAACTCCGTGGGGGAGGAGC
	TGTACAAGCTGAGTATCTTCAACTTCCTCCTCACCGTGGCCTTCGCCTTCCTGGTCACCCTGCCTCG
	GAGGCTGCTGGTGGACCGGTTCTCAGGCCGGTTCTGGGCCTGGCTGGAACGGGAGGAGTTCCTGGTC
	CCCAAGAATGTGCTGGACATCGTGGCGGGGCAGACGGTCACCTGGATGGGCCTCTTCTACTGCCCCC
	TGCTGCCCCTGCTGAATAGCGTCTTCCTCTTCCTCACCTTCTACATCAAGAAGTACACCCTCCTGAA
	GAACTCCAGGGCATCTTCGCGGCCCTTCCGTGCCTCCAGCTCCACCTTCTTCTTCCAGCTAGTGCTC
	CTCCTGGGCCTGCTTCTGGCTGCAGTGCCCCTGGGCTATGTGGTCAGCAGCATCCACTCCTCCTGGG
	ACTGCGGCCTCTTCACCAACTACTCAGCACCCTGGCAAGTGGTCCCGGAGCTGGTGGCCCTTGGGCT
	CCCGCCCATTGGCCAGCGTGCCCTCCACTACCTGGGCTCCCACGCCTTCAGCTTCCCCCTCCTCATC
	ATGCTCAGCCTTGTCCTGACGGTGTGCGTCTCCCAGACCCAGGCCAATGCCAGGGCCATCCACAGGC
	TCCGGAAGCAGCTGGTGTGGCAGGTTCAGGAGAAGTGGCACCTGGTGGAGGACCTGTCGCGACTGCT
	GCCGGAGCCAGGCCCGAGCGACTCTCCGGGCCCCAAGTACCCTGCCTCCCAAGCTTCGCGCCCGCAG
	TCCTTCTGCCCCGGATGCCCATGCCCTGGCTCCCCGGGCCACCAGGCCCCGCGGCCGGGCCCCTCCG
	TCGTGGATGCCGCGGGACTGCGTTCCCCTTGCCCTGGACAGCACGGTGCCCCGGCCTCCGCCCGCAG
	ATTCCGCTTCCCCAGCGGCGCGGAGCTGTAACCCCGACCCCTGCCTCCCCGAAGCCTCCCTGGGGCC
	CCTTCAGGCCTCCTTA
	ORF Start: ATG at 352		ORF Stop: TAA at 2575
	SEQ ID NO: 116	741 aa	MW at 83147.1 kD
NOV19b,	MLLPRSVSSERAPGVPEPEELWEAEMERLRGSGTPVRGLPYAMMDKRLIWQLREPAGVQTLRWQRWQ
CG162687-01
Protein Sequence	RRRQTVERRLREAAQRLARGLGLWEGALYEIGGLFGTGIRSYFTFLRFLLLLNLLSLLLTASFVLLP
	LVWLRPPDPGPTLNLTLQCPGSRQSPPGVLRFHNQLWHVLTGRAFTNTYLFYGAYRVGPESSSVYSI
	RLAYLLSPLACLLLCFCGTLRRMVKGLPQKTLLGQGYQAPLSAKVFSSWDFCIRVQEAATIKKHEIS
	NEFKVELEEGRRFQLMQQQTRAQTACRLLSYLRVNVLNGLLVVGAISAIFWATKYSQDNKEVSGNCI
	HLILARTAGESLFLLLQYLPPGVIALVNFLGPLLFTFLVQLENYPPNTEVNLTLIWCVVLKLASLGM
	FSVSLGQTILCIGRDKSSCESYGYNVCDYQCWENSVGEELYKLSIFNFLLTVAFAFLVTLPRRLLVD
	RFSGRFWAWLEREEFLVPKNVLDIVAGQTVTWMGLFYCPLLPLLNSVFLFLTFYIKKYTLLKNSRAS
	SRPFRASSSTFFFQLVLLLGLLLAAVPLGYVVSSIHSSWDCGLFTNYSAPWQVVPELVALGLPPIGQ
	RALHYLGSHAFSFPLLIMLSLVLTVCVSQTQANARAIHRLRKQLVWQVQEKWHLVEDLSRLLPEPGP
	SDSPGPKYPASQASRPQSFCPGCPCPGSPGHQAPRPGPSVVDAAGLRSPCPGQHGAPASARRFRFPS
	GAEL

[0470] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 19B.

TABLE 19B
Comparison of NOV19a against NOV19b.
	NOV19a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV19b	1..726	722/741 (97%)
	1..741	723/741 (97%)

[0471] Further analysis of the NOV19a protein yielded the following properties shown in Table 19C.

TABLE 19C
Protein Sequence Properties NOV19a
SignalP analysis:	No Known Signal Sequence Predicted
PSORT II	PSG:	a new signal peptide prediction method
analysis:		N-region:	length 11;	pos. chg 2;	neg. chg 1
		H-region:	length 5;	peak value	−6.15
		PSG score: −10.55
	GvH:	von Heijne's method for signal seq. recognition
		GvH score (threshold: −2.1): −5.78
		possible cleavage site: between 60 and 61
	>>> Seems to have no N-terminal signal peptide
	ALOM:	Klein et al's method for TM region allocation
		Init position for calculation: 1
		Tentative number of TMS(s) for the threshold 0.5: 9
		INTEGRAL	Likelihood = −7.48	Transmembrane 116-132
		INTEGRAL	Likelihood = −3.72	Transmembrane 203-219
		INTEGRAL	Likelihood = −8.65	Transmembrane 304-320
		INTEGRAL	Likelihood = −7.01	Transmembrane 343-359
		INTEGRAL	Likelihood = −4.04	Transmembrane 374-390
		INTEGRAL	Likelihood = −5.47	Transmembrane 430-446
		INTEGRAL	Likelihood = −3.19	Transmembrane 489-505
		INTEGRAL	Likelihood = −8.70	Transmembrane 537-553
		INTEGRAL	Likelihood = −6.69	Transmembrane 599-615
		PERIPHERAL	Likelihood = 5.04 (at 570)
		ALOM score: −8.70 (number of TMSs: 9)
	MTOP:	Prediction of membrane topology (Hartmann et al.)
		Center position for calculation: 123
		Charge difference: −2.0 C(0.0) − N(2.0)
		N >= C: N-terminal side will he inside
	>>> membrane topology: type 3a
	MITDISC:	discrimination of mitochondrial targeting seq
		R content:	2	Hyd Moment (75):	9.58
		Hyd Moment (95):	7.17	G content:	1
		D/E content:	2	S/T content:	3
		Score: −4.19
	Gavel:	prediction of cleavage sites for mitochondrial preseq
		R-2 motif at 15 PRS|VS
	NUCDISC:	discrimination of nuclear localization signals
		pat4: none
		pat7: none
		bipartite: none
		content of basic residues: 9.9%
		NLS Score: −0.47
	KDEL:	ER retention motif in the C-terminus: none
	ER Membrane Retention Signals:
		XXRR-like motif in the N-terminus: LLPR
	none
	SKL:	peroxisomal targeting signal in the C-terminus: none
	PTS2:	2nd peroxisomal targeting signal: none
	VAC:	possible vacuolar targeting motif: none
	RNA-binding motif: none
	Actinin-type actin-binding motif:
		type 1: none
		type 2: none
	NMYR:	N-myristoylation pattern: none
	Prenylation motif: none
	memYQRL:	transport motif from cell surface to Golgi: none
	Tyrosines in the tail: none
	Dileucine motif in the tail: none
	checking 63 PROSITE DNA binding motifs:
	Leucine zipper pattern (PS00029): *** found ***
	LSPLACLLLCFCGTLRRMVKGL at 207
	LFLLLQYLPPGVIALVNFLGPL at 332
	LSIFNFLLTVAFAFLVTLPRRL at 430
	none
	checking 71 PROSITE ribosomal protein motifs: none
	checking 33 PROSITE prokaryotic DNA binding motifs: none
	NNCN:	Reinhardt's method for Cytoplasmic/Nuclear discrimination
		Prediction: cytoplasmic
		Reliability: 94.1
	COIL:	Lupas's algorithm to detect coiled-coil regions
	58 Q	0.53
	59 T	0.53
	60 L	0.53
	61 R	0.53
	62 W	0.53
	63 Q	0.53
	64 R	0.53
	65 W	0.53
	66 Q	0.53
	67 R	0.53
	68 R	0.53
	69 R	0.53
	70 Q	0.53
	71 T	0.53
	72 V	0.53
	73 E	0.53
	74 R	0.53
	75 R	0.53
	76 L	0.53
	77 R	0.53
	78 E	0.53
	79 A	0.53
	80 A	0.53
	81 Q	0.53
	82 R	0.53
	83 L	0.53
	84 A	0.53
	85 R	0.53
	total: 28 residues
	Final Results (k = 9/23):
	77.8%:	endoplasmic reticulum
	11.1%:	nuclear
	11.1%:	vesicles of secretory system
	>> prediction for CG162687-02 is end (k = 9)

[0472] 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 19D.

TABLE 19D
Geneseq Results for NOV19a
		NOV19a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAB74730	Human membrane associated	35..639	225/626 (35%)	2e−90
	protein MEMAP-36-Homo	83..689	322/626 (50%)
	sapiens, 706 aa.
	[WO200112662-A2,
	22 FEB. 2001]
AAY94906	Human secreted protein clone	83..639	212/571 (37%)	2e−87
	rb649_3 protein sequence	15..572	303/571 (52%)
	SEQ ID NO:18-Homo
	sapiens, 589 aa.
	[WO200009552-A1,
	24 FEB. 2000]
AAM40237	Human polypeptide SEQ ID	128..559	161/446 (36%)	2e−62
	NO 3382-Homo sapiens,	2..436	231/446 (51%)
	436 aa. [WO200153312-A1,
	26 JUL. 2001]
AAO17232	Human secreted protein	332..639	123/309 (39%)	6e−55
	homologous protein SEQ ID	10..317	176/309 (56%)
	NO: 131-Homo sapiens,
	334 aa. [WO200228877-A1,
	11 APR. 2002]
ABG64736	Human albumin fusion	427..639	87/213 (40%)	5e−38
	protein #1411-Homo	1..212	124/213 (57%)
	sapiens, 229 aa.
	[WO200177137-A1,
	18 OCT. 2001]

[0473] 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 19E.

TABLE 19E
Public BLASTP Results for NOV19a
		NOV18a	Identities/
Protein		Residues/	Similarities for
Accession	Protein/Organism/	Match	the Matched	Expect
Number	Length	Residues	Portion	Value
AAL25837	EVIN2-Homo sapiens	1..726	722/726 (99%)	0.0
	(Human), 726 aa.	1..726	723/726 (99%)
Q8NF04	FLJ00400 protein-Homo	1..726	722/726 (99%)	0.0
	sapiens (Human), 782 aa	57..782	723/726 (99%)
	(fragment).
Q8N358	Hypothetical protein-Homo	1..228	221/228 (96%)	e−128
	sapiens (Human), 287 aa.	1..228	224/228 (97%)
Q8TBS7	Similar to hypothetical	35..639	225/626 (35%)	5e−90
	protein FLJ21240-Homo	83..689	322/626 (50%)
	sapiens (Human), 706 aa.
Q9H766	Hypothetical protein	260..647	146/401 (36%)	2e−67
	FLJ21240-Homo sapiens	2..394	236/401 (58%)
	(Human), 402 aa.

[0474] PFam analysis predicts that the NOV19a protein contains the domains shown in the Table 19F.

TABLE 19F
Domain Analysis of NOV19a
		Identities/Similarities
	NOV19a Match	for the Matched	Expect
Pfam Domain	Region	Region	Value

Example 20

[0475] 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: 117	1143 bp
NOV20a,	GGCCGCCCGGGGCCATGGCGACACTCAGCTTCGTCTTCCTGCTGCTGGGGGCAGTGTCCTGGCCTCC
CG162738-01
DNA Sequence	GGCTTCTGCCTCCGGCCAGGAGTTCTGGCCCGGACAATCGGCGGCCGATATTCTGTCGGGGGCGGCT
	TCCCGCAGACCGTATCTTCTGTATGACGTCAACCCCCCGGAAGGCTTCAACCTGCGCAGGGATGTCT
	ATATCCGAATCGCCTCTCTCCTGAAGACTCTGCTGAAGACGGAGGAGTGGGTGCTTGTCCTGCCTCC
	ATGGGGCCGCCTCTATCACTGGCAGAGTCCTGACATCCACCAGGTCCGGATTCCCTGGTCTGAGTTT
	TTTGATCTTCCAAGTCTCAATAAAAACATCCCCGTCATCGAGTATGAGCAGTTCATCGCAGAATCTG
	GTGGGCCCTTTATTGACCAGGTTTACGTCCTGCAAAGTTACGCAGAGGGGTGGAAAGAAGGGACCTG
	GGAAGAGAAGGTGGACGAGCGGCCGTGTATTGATCAGCTCCTGTACTCCCAGGACAAGCACGAGTAC
	TACAGAGGATGGTTTTGGGGTTATGAGGAGACCAGGGGTCTAAACGTCTCCTGTCTGTCCGTCCAGG
	GCTCAGCCTCCATCGTGGCGCCCCTGCTGCTGAGAAACACATCAGCCCGGTCCGTGATGTTAGACAG
	AGCCGAGAACCTACTTCACGACCACTATGGAGGGAAAGAATACTGGGATACCCGTCGCAGCATGGTG
	TTTGCCAGGCACCTGCGGGAGGTGGGAGACGAGTTCAGGAGCAGACATCTCAACTCCACGGACGACG
	CAGACAGGATCCCCTTCCAGGAGGACTGGATGAAGATGAAGGTCAAGCTGGGCTCCGCGCTAGGGGG
	CCCCTACCTGGGAGTCCACCTGAGAAGAAAAGATTTCATCTGGGGTCACAGACAGGATGTACCCAGT
	CTGGAAGGGGCCGTGAGGAAGATCCGCAGCCTCATGAAGACCCACCGGCTGGACAAGGTGTTTGTGG
	CCACAGATGCCGTCAGAAAGGAAACAGTGCCTTTTTCATCAGTTGCATTTTCCAGGCTGAGAGCTGT
	ATAAAACATTTTGGACTGTGACCATGTACCTTCCTTTTTAAGAAAAATAAACTGCTTTATGGAAGTT
	AAAA
	ORF Start: ATG at 15		ORF Stop: TAA at 1074
	SEQ ID NO: 118	353 aa	MW at 40781.0 kD
NOV20a,	MATLSFVFLLLGAVSWPPASASGQEFWPGQSAADILSGAASRRRYLLYDVNPPEGFNLRRDVYIRIA
CG162738-01
Protein Sequence	SLLKTLLKTEEWVLVLPPWGRLYHWQSPDIHQVRIPWSEFFDLPSLNKNIPVIEYEQFIAESGGPFI
	DQVYVLQSYAEGWKEGTWEEKVDERPCIDQLLYSQDKHEYYRGWFWGYEETRGLNVSCLSVQGSASI
	VAPLLLRNTSARSVMLDRAENLLHDHYGGKEYWDTRRSMVFARHLREVGDEFRSRHLNSTDDADRIP
	FQEDWMKMKVKLGSALGGPYLGVHLRRKDFIWGHRQDVPSLEGAVRKIRSLMKTHRLDKVFVATDAV
	RKETVPFSSVAFSRLRAV
	SEQ ID NO: 119	960 bp
NOV20b,	GGCCGCCCGGGGCCATGGCGACACTCAGCTTCGTCTTCCTGCTGCTGGGGGCAGTGTCCTGGCCTCC
CG162738-02
DNA Sequence	GGCTTCTGCCTCCGGCCAGGAGTTCTGGCCCGGACAATCGGCGGCCGATATTCTGTCGGGGGCGGCT
	TCCCGCAGACGGTATCTTCTGTATGACGTCAACCCCCCGGAAGGCTTCAACCTGCGCAGGGATGTCT
	ATATCCGAATCGCCTCTCTCCTGAAGACTCTGCTGAAGACGGAGGAGTGGGTGCTTGTCCTGCCTCC
	ATGGGGCCGCCTCTATCACTGGCAGAGTCCTGACATCCACCAGGTCCGGATTCCCTGGTCTGAGTTT
	TTTGATCTTCCAAGTCTCAATAAAAACATCCCCGTCATCGAGTATGAGCAGTTCATCGCAGGAAGAC
	GCACTGCGTGTGGAGTATGCTTCGTGGTGTCTCAGTGCAGCGCCAGGGATAAAGAATCTGGTGGGCC
	CTTTATTGACCAGGTTTACGTCCTGCAAAGTTACGCAGAGGGGTGGAAAGAAGGGACCTGGGAAGAG
	AAGGTGGACGAGCGGCCGTGTATTGATCAGCTCCTGTACTCCCAGGACAAGCACGAGTCCTCACTGA
	GCAGCCACTTTCCACATCTGCTAGAGGAACAGTGACATGGACACCTGTGACAGAGAGAGGACAGTTA
	GGAGGGACAGACAGCTCTTCCTTTCGGAGCCTGGCTAGTCTAGGACATCACCTTGCTGTGTCTTCTC
	AAGCTTTTAAAATTGACCCTGAACGTGTGACAGGGTCCTATGGTGTTACTCAAAGCTGTGCAGGGTA
	AATGATGACATATTTATTCTTTTTCCATTTGTTCTAGAAACAGTGCCTTTTTCATCAGTTGCATTTT
	CCAGGCTGAGAGCTGTATAAAACATTTTGGACTGTGACCATGTACCTTCCTTTTTAAGAAAAATAAA
	CTGCTTTATGGAAAAAAAAAAA
	ORF Start: ATG at 15		ORF Stop: TGA at 636
	SEQ ID NO: 120	207 aa	MW at 23705.6 kD
NOV20b,	MATLSFVFLLLGAVSWPPASASGQEFWPGQSAADILSGAASRRRYLLYDVNPPEGFNLRRDVYIRIA
CG162738-02
Protein Sequence	SLLKTLLKTEEWVLVLPPWGRLYHWQSPDIHQVRIPWSEFFDLPSLNKNIPVIEYEQFIAGRRTACG
	VCFVVSQCSARDKESGGPFIDQVYVLQSYAEGWKEGTWEEKVDERPCIDQLLYSQDKHESSLSSHFP
	HLLEEQ
	SEQ ID NO: 121	960 bp
NOV20c,	GGCCGCCCGGGGCCATGGCGACACTCAGCTTCGTCTTCCTGCTGCTGGGGGCAGTGTCCTGGCCTCC
CG162738-03
DNA Sequence	GGCTTCTGCCTCCGGCCAGGAGTTCTGGCCCGGACAATCGGCGGCCGATATTCTGTCGGGGGCGGCT
	TCCCGCAGACGGTATCTTCTGTATGACGTCAACCCCCCGGAAGGCTTCAACCTGCGCAGGGATGTCT
	ATATCCGAATCGCCTCTCTCCTGAAGACTCTGCTGAAGACGGAGGAGTGGGTGCTTGTCCTGCCTCC
	ATGGGGCCGCCTCTATCACTGGCAGAGTCCTGACATCCACCAGGTCCGGATTCCCTGGTCTGAGTTT
	TTTGATCTTCCAAGTCTCAATAAAAACATCCCCGTCATCGAGTATGAGCAGTTCATCGCAGGAAGAC
	GCACTGCGTGTGGAGTATGCTTCGTGGTGTCTCAGTGCAGCGCCAGGGATAAAGAATCTGGTGGGCC
	CTTTATTGACCAGGTTTACGTCCTGCAAAGTTACGCAGAGGGGTGGAAAGAAGGGACCTGGGAAGAG
	AAGGTGGACGAGCGGCCGTGTATTGATCAGCTCCTGTACTCCCAGGACAAGCACGAGTCCTCACTGA
	GCAGCCACTTTCCACATCTGCTAGAGGAACAGTGACATGGACACCTGTGACAGAGAGAGGACAGTTA
	GGAGGGACAGACAGCTCTTCCTTTCGGAGCCTGGCTAGTCTAGGACATCACCTTGCTGTGTCTTCTC
	AAGCTTTTAAAATTGACCCTGAACGTGTGACAGGGTCCTATGGTGTTACTCAAAGCTGTGCAGGGTA
	AATGATGACATATTTATTCTTTTTCCATTTGTTCTAGAAACAGTGCCTTTTTCATCAGTTGCATTTT
	CCAGGCTGAGAGCTGTATAAAACATTTTGGACTGTGACCATGTACCTTCCTTTTTAAGAAAAATAAA
	CTGCTTTATGGAAAAAAAAAAA
	ORF Start: ATG at 15		ORF Stop: TGA at 636
	SEQ ID NO: 122	207 aa	MW at 23705.6 kD
NOV20c,	MATLSFVFLLLGAVSWPPASASGQEFWPGQSAADILSGAASRRRYLLYDVNPPEGFNLRRDVYIRIA
CG162738-03
Protein Sequence	SLLKTLLKTEEWVLVLPPWGRLYHWQSPDIHQVRIPWSEFFDLPSLNKNIPVIEYEQFIAGRRTACG
	VCFVVSQCSARDKESGGPFIDQVYVLQSYAEGWKEGTWEEKVDERPCIDQLLYSQDKHESSLSSHFP
	HLLEEQ

[0476] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 20B.

TABLE 20B
Comparison of NOV20a against NOV20b and NOV20c.
	NOV20a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV20b	1..173	173/193 (89%)
	1..193	173/193 (89%)
NOV20c	1..173	173/193 (89%)
	1..193	173/193 (89%)

[0477] Further analysis of the NOV20a protein yielded the following properties shown in Table 20C.

TABLE 20C
Protein Sequence Properties NOV20a
SignalP analysis:	Cleavage site between residues 22 and 23
PSORT II	PSG:	a new signal peptide prediction method
analysis:		N-region:	length 0;	pos. chg 0;	neg. chg 0
		H-region:	length 24;	peak value	11.40
		PSG score:	7.00
	GvH:	von Heijne's method for signal seq. recognition
		GvH score (threshold: −2.1): 3.12
		possible cleavage site: between 21 and 22
	>>> Seems to have a cleavable signal peptide (1 to 21)
	ALOM:	Klein et al's method for TM region allocation
		Init position for calculation: 22
		Tentative number of TMS(s) for the threshold 0.5: 0
		number of TMS(s) .. fixed
		PERIPHERAL	Likelihood = 0.53 (at 190)
		ALOM score: 0.53 (number of TMSs: 0)
	MTOP:	Prediction of membrane topology (Hartmann et al.)
		Center position for calculation: 10
		Charge difference: −3.0 C(−2.0) − N(1.0)
		N >= C: N-terminal side will be inside
	MITDISC:	discrimination of mitochondrial targeting seq
		R content:	0	Hyd Moment (75):	2.26
		Hyd Moment (95):	1.40	G content:	2
		D/E content:	1	S/T content:	5
		Score: −5.53
	Gavel:	prediction of cleavage sites for mitochondrial preseq
		cleavage site motif not found
	NUCDISC:	discrimination of nuclear, localization signals
		pat4: none
		pat7: none
		bipartite: none
		content of basic residues: 12.7%
		NLS Score: −0.47
	EDEL:	ER retention motif in the C-terminus: none
	ER Membrane Retention Signals: none
	SKL:	peroxisomal targeting signal in the C-terminus: none
	PTS2:	2nd peroxisomal targeting signal: none
	VAC:	possible vacuolar targeting motif: none
	RNA-binding motif: none
	Actinin-type actin-binding motif:
		type 1: none
		type 2: none
	NMYR:	N-myristoylation pattern: none
	Prenylation motif: none
	memYQRL:	transport motif from cell surface to Golgi: none
	Tyrosines in the tail: none
	Dileucine motif in the tail: none
	checking 63 PROSITE DNA binding motifs: none
	checking 71 PROSITE ribosomal protein motifs: none
	checking 33 PROSITE prokaryotic DNA binding motifs: none
	NNCN:	Reinhardt's method for Cytoplasmic/Nuclear discrimination
		Prediction: cytoplasmic
		Reliability: 94.1
	COIL:	Lupas's algorithm to detect coiled-coil regions
		total: 0 residues
	Final Results (k = 9/23)
	22.2%:	extracellular, including cell wall
	22.2%:	vacuolar
	22.2%:	mitochondrial
	22.2%:	endoplasmic reticulum
	11.1%:	Golgi
	>> prediction for CG162738-01 is exc (k = 9)

[0478] 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 20D.

TABLE 20D
Geneseq Results for NOV20a
		NOV20a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAB40332	Human ORFX ORF96	1..338	338/338 (100%)	0.0
	polypeptide sequence SEQ	5..342	338/338 (100%)
	ID NO:192-Homo sapiens,
	428 aa. [WO200058473-A2,
	5 OCT. 2000]
AAY11376	Human 5′ EST secreted	1..134	130/134 (97%)	8e−72
	protein SEQ ID No 198-	1..134	130/134 (97%)
	Homo sapiens, 134 aa.
	[WO9906551-A2,
	11 FEB. 1999]
ABB69800	Drosophila melanogaster	45..353	124/334 (37%)	6e−49
	polypeptide SEQ ID NO	73..396	175/334 (52%)
	36192-Drosophila
	melanogaster, 490 aa.
	[WO200171042-A2,
	27 SEP. 2001]
ABB48718	Listeria monocytogenes	56..175	29/123 (23%)	2.1
	protein #1422-Listeria	55..166	55/123 (44%)
	monocytogenes, 657 aa.
	[WO200177335-A2,
	18 OCT. 2001]

[0479] 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 20E.

TABLE 20E
Public BLASTP Results for NOV20a
		NOV20a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
T14795	hypothetical protein	1..338	338/338 (100%)	0.0
	DKFZp434E171.1-human,	4..341	338/338 (100%)
	383 aa (fragment).
Q9Y2G5	Protein C21orf80-Homo	1..338	338/338 (100%)	0.0
	sapiens (Human), 424 aa.	1..338	338/338 (100%)
Q8VHI3	Protein C21orf80 homolog-	1..338	309/338 (91%)	0.0
	Mus musculus (Mouse), 429	1..338	323/338 (95%)
	aa.
Q8WR51	C210RF80-Caenorhabditis	40..338	133/305 (43%)	2e−68
	elegans, 424 aa.	38..334	201/305 (65%)
Q9W589	EG:BACN32G11.6 protein	45..353	124/334 (37%)	2e−48
	(GH07929P)-Drosophila	73..396	175/334 (52%)
	melanogaster (Fruit fly), 490
	aa.

[0480] PFam analysis predicts that the NOV20a protein contains the domains shown in the Table 20F.

TABLE 20F
Domain Analysis of NOV20a
		Identities/Similarities
	NOV20a Match	for the Matched	Expect
Pfam Domain	Region	Region	Value

Example 21

[0481] 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: 123	2275 bp
NOV21a,	CTGCCCCGGTACTCACAAGCTTCTCGGCCCCGACCTTCGCCCTGGGAGGTTCTGGCCAGGTGCCGGG
CG163175-01
DNA Sequence	AGGGGCGCTGTGTCGAGGGCGATCCCCCCAAAGCAGCGTCCCGTGCTAAAGGTACTGCTTAGGATGA
	ATATGATTTGGAGAAATTCCATTTCTTGTCTAAGGCTAGGAAAGGTGCCACACAGATACCAAAGTGG
	TTACCACCCAGTGGCCCCTCTGGGATCAAGGATTTTAACTGACCCAGCCAAAGTTTTTGAACACAAC
	ATGTGGGATCACATGCAGTGGTCTAAGGAAGAAGAAGCAGCAGCCAGAAAAAAAGTAAAAGAAAACT
	CAGCTGTGCGAGTCCTTCTGGAAGAGCAAGTTAAGTATGAGAGAGAAGCTAGTAAATACTGGGACAC
	ATTTTACAAGATTCATAAGAATAAGTTTTTCAAGGATCGTAATTGGCTGTTGAGGGAATTTCCTGAA
	ATTCTTCCAGTTGATCAAAAACCTGAAGAGAAGGCGAGAGAATCATCATGGGATCATGTAAAAACTA
	GTGCTACAAATCGTTTCTCAAGAATGCACTGTCCTACTGTGCCTGATGAAAAAAATCATTATGAGAA
	AAGTTCTGGTTCTTCAGAAGGTCAAAGCAAAACAGAATCTGATTTTTCCAACCTAGACTCTGAAAAA
	CACAAAAAAGGACCTATGGAGACTGGATTGTTTCCTGGTAGCAATGCCACTTTCAGGATACTAGAGG
	TTGGTTGTGGAGCTGGAAATAGTGTGTTTCCAATTTTGAACACTTTGGAGAACTCTCCGGAGTCCTT
	TCTGTATTGTTGTGATTTTGCTTCTGGAGCTGTGGAGCTCGTAAAGTCACACTCGTCCTACAGAGCA
	ACCCAGTGTTTTGCCTTTGTTCATGATGTATGTGATGATGGCTTACCTTACCCTTTTCCAGATGGGA
	TCCTGGATGTCATTCTCCTTGTCTTTGTGCTCTCTTCTATTCATCCTGACAGGATGCAAGGTGTTGT
	AAACCGACTGTCCAAGTTACTGAAACCTGGGGGAATGCTGTTATTTCGAGACTATGGAAGATATGAT
	AAGACTCAGCTTCGTTTTAAAAAGGGACATTGTTTATCTGAAAATTTTTATGTTCGAGGAGATGGTA
	CCAGAGCATATTTCTTTACAAAAGGGGAAGTCCACAGTATGTTCTGCAAAGCCAGTTTAGATGAAAA
	GCAAAATCTGGTTGATCGCCGCTTACAAGTTAATAGGAAAAAACAAGTGAAAATGCACCGAGTGTGG
	ATTCAAGGCAAATTCCAGAAACCATTGCACCAGACTCAGAATAGCTCCAATATGGTATCTACACTCC
	TTTCACAAGACTGAACTTTGTAACATGTTAAGGTACAAAGCCAGAGGACTGTGCTATTCAAGGACTA
	CTGTAAGTCTATTGTTTCTCAAAAGACAATGAGAAAAAAAGAAGAGAATTTGTATTTCCTGCCGTTT
	TGTCATAGGTGAGCTCCTTTGTGCATTTTAAGCACATGTAAGTGGTTCAGCACAGTATGCCTTTTTC
	TGTGCTTTGAAAACTTGATATGCTCAAGCTTGTTTGAATTTATTACATCTAACCATTTTGCTTGTTC
	CTTGATTTTTATAAGCATTCAATTAAGTTAGTATTATGTCAAGTAATTTTGAGAAAATGTAACTTGA
	CATTTTTTGCAAGTAAAAAAAATTGTTTATTTGTTTAGGCTTAGTAAACCAGTTCCCAAACACAGTC
	AGACTCTTCCCATTGTCATCTGATTGCAGAGAGAAAGCACACCTTATTTCCAGGGAAAGCTACAACA
	AGCCCAAGGTCAAAGTGTATTATTTTTTGTCTTGTTGTTGTCTATTTTCTCCCAATTTTTTTTTGAA
	ATTCAGAGGCTCATATCTGAAATAGAATTTTAGTTCCTCTTTCCTTTCCTAAAATTGGGGAAGTACA
	GCCCATGCTGACATTATTTTCAGGCTATTCTTAGATATACAAGTTGTTAGGCCAGGTGCAATGGCTC
	GCACCTGTAATCCCAGCACTTTGGGGGGCTGAGGCAGGCAGATCGCTTGAGCTCAGGAGTTCAAGAC
	CAGCCTGGACAACATGGCAAAACCCTGTCTCTCCCAAGAATACAAAAATTAGCCAGGCATGGTGGCA
	CACACCTGTGGTCCCAGCTACTCAGGAGACTGAGGTGGGAGGATCGCTTGAGCCTCGGAGGCGGAGG
	TTGCAGTGAGCTGAGATTGTACCACTGCGCTCCAAACTGGGTGACATGGTGAGACCTTGTCTCC
	ORF Start: ATG at 131		ORF Stop: TGA at 1352
	SEQ ID NO: 124	407 aa	MW at 46992.1 kD
NOV21a,	MNMIWRNSISCLRLGKVPHRYQSGYHPVAPLGSRILTDPAKVFEHNMWDHMQWSKEEEAAARKKVKE
CG163175-01
Protein Sequence	NSAVRVLLEEQVKYEREASKYWDTFYKIHKNKFFKDRNWLLREFPEILPVDQKPEEKARESSWDHVK
	TSATNRFSRMHCPTVPDEKNHYEKSSGSSEGQSKTESDFSNLDSEKHKKGPMETGLFPGSNATFRIL
	EVGCGAGNSVFPILNTLENSPESFLYCCDFASGAVELVKSHSSYRATQCFAFVHDVCDDGLPYPFPD
	GILDVILLVFVLSSIHPDRMQGVVNRLSKLLKPGGMLLFRDYGRYDKTQLRFKKGHCLSENFYVRGD
	GTRAYFFTKGEVHSMFCKASLDEKQNLVDRRLQVNRKKQVKMHRVWIQGKFQKPLHQTQNSSNMVST
	LLSQD

[0482] Further analysis of the NOV21a protein yielded the following properties shown in Table 21B.

TABLE 21B
Protein Sequence Properties NOV21a
SignalP analysis:	No Known Signal Sequence Predicted
PSORT II	PSG:	a new signal peptide prediction method
analysis:		N-region:	length 6;	pos. chg 1;	neg. chg 0
		H-region:	length 6;	peak value −2.73
		PSG score: −7.12
	GvH:	von Heijne's method for signal seq. recognition
		GvH score (threshold: −2.1): −9.99
		possible cleavage Site: between 37 and 38
	>>> Seems to have no N-terminal signal peptide
	ALOM:	Klein et al's method for TM region allocation
		Init position for calculation: 1
		Tentative number of TMS(s) for the threshold 0.5: 1
		Number of TMS(s) for threshold 0.5: 1
		INTEGRAL	Likelihood = −3.66	Transmembrane 269-285
		PERIPHERAL	Likelihood = 4.72 (at 200)
		ALOM score: −3.66 (number of TMSs: 1)
		MTOP:	Prediction of membrane topology (Hartmann et al.)
		Center position for calculation: 276
		Charge difference: 6.5 C(2.5) − N(−4.0)
		C > N: C-terminal side will be inside
	>>> membrane topology: type 1b (cytoplasmic tail 269 to 407)
	MITDISC:	discrimination of mitochondrial targeting seq
		R content:	4	Hyd Moment(75):	10.77
		Hyd Moment(95):	11.10	G content:	3
		D/E content:	1	S/T content:	5
		Score: −0.04
	Gavel:	prediction of cleavage sites for mitochondrial preseq
		R-2 motif at 44 SRI|LT
	NUCDISC:	discrimination of nuclear localization signals
		pat4: KHKK (3) at 180
		pat7: none
		bipartite: none
		content of basic residues: 14.7%
		NLS Score: −0.29
	KDEL:	ER retention motif in the C-terminus: none
		ER Membrane Retention Signals: none
	SKL:	peroxisomal targeting signal in the C-terminus: none
	PTS2:	2nd peroxisomal targeting signal: none
	VAC:	possible vacuolar targeting motif: none
	RNA-binding motif: none
	Actinin-type actin-binding motif:
		type 1: none
		type 2: none
	NMYR:	N-myristoylation pattern: none
	Prenylation motif: none
	memYQRL:	transport motif from cell surface to Golgi: none
	Tyrosines in the tail: too long tail
	Dileucine motif in the tail: found
	LL at 275
	LL at 298
	LL at 305
	LL at 403
	checking 63 PROSITE DNA binding motifs: none
	checking 71 PROSITE ribosomal protein motifs: none
	checking 33 PROSITE prokaryotic DNA binding motifs: none
	NNCN:	Reinhardt's method for Cytoplasmic/Nuclear discrimination
		Prediction: nuclear
		Reliability: 55.5
	COIL:	Lupas's algorithm to detect coiled-coil regions
	total: 0 residues
	Final Results (k = 9/23):
	65.2%:	nuclear
	17.4%:	mitochondrial
	8.7%:	cytoplasmic
	4.3%:	plasma membrane
	4.3%:	vesicles of secretory system
	>> prediction for CG163175-01 is nuc (k = 23)

[0483] 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
		NOV20a	Identities/
		Residues/	Similarities
Geneseq	Protein/Organism/Length	Match	for the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAB94868	Human protein sequence	51..287	237/237 (100%)	e−140
	SEQ ID NO:16072-Homo	1..237	237/237 (100%)
	sapiens, 241 aa.
	[EP1074617-A2,
	7 FEB. 2001]
AAM78551	Human protein SEQ ID NO	32..390	200/360 (55%)	e−108
	1213-Homo sapiens, 415	58..410	256/360 (70%)
	aa. [WO200157190-A2,
	9 AUG. 2001]
ABB80946	Human basophilic	49..390	188/343 (54%)	e−100
	45.32-Homo sapiens, 412	72..407	243/343 (70%)
	aa. [CN1341659-A,
	27 MAR. 2002]
AAM79535	Human protein SEQ ID NO	49..390	188/343 (54%)	e−100
	3181-Homo sapiens, 384	44..379	243/343 (70%)
	aa. [WO200157190-A2,
	9 AUG. 2001]
AAB87436	Human gene 22 encoded	125..287	163/163 (100%)	3e−94
	secreted protein fragment,	1..163	163/163 (100%)
	SEQ ID NO:177-Homo
	sapiens, 167 aa.
	[WO200118022-AL,
	15 MAR. 2001]

[0484] 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
		NOV20a	Identities/
Protein		Residues/	Similarities for
Accession		Match	the Matched	Expect
Number	Protein/Organism/Length	Residues	Portion	Value
Q9H825	Hypothetical protein	51..287	237/237 (100%)	e−140
	FLJ13984-Homo sapiens	1..237	237/237 (100%)
	(Human), 241 aa.
Q9P0B5	HSPC266-Homo sapiens	32..390	199/360 (55%)	e−107
	(Human), 376 aa (fragment).	19..371	255/360 (70%)
Q9NUI8	Hypothetical protein	79..390	172/313 (54%)	8e−90
	FLJ11350-Homo sapiens	3..308	219/313 (69%)
	(Human), 313 aa.
Q99K17	Similar to hypothetical	51..287	162/238 (68%)	1e−87
	protein FLJ13984-Mus	1..227	183/238 (76%)
	musculus (Mouse), 254 aa.
Q961Z6	Hypothetical protein-Homo	191..390	134/200 (67%)	2e−76
	sapiens (Human), 242 aa.	39..237	164/200 (82%)

[0485] PFam analysis predicts that the NOV21a protein contains the domains shown in the Table 21E.

TABLE 21E
Domain Analysis of NOV21a
		Identities/Similarities
	NOV21a Match	for the Matched	Expect
Pfam Domain	Region	Region	Value

Example 22

[0486] 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: 125	1033 bp
NOV22a,	CGCCCAGCGACGTGCGGGCGGCCTGGCCCGCGCCCTCCCGCGCCCGGCCTGCGTCCCGCGCCCTGCG
CG163259-01
DNA Sequence	CCACCGCCGCCGAGCCGCAGCCCGCCGCGCGCCCCCGGCAGCGCCGGCCCCATGCCCGCCGGCCGCC
	GGGGCCCCGCCGCCCAATCCGCGCGGCGGCCGCCGCCGTTGCTGCCCCTGCTGCTGCTGCTCTGCGT
	CCTCGGGGCGCCGCGAGCCGGATCAGGAGCCCACACAGCTGTGATCAGTCCCCAGGATCCCACGCTT
	CTCATCGGCTCCTCCCTGCTGGCCACCTGCTCAGTGCACGGAGACCCACCAGGAGCCACCGCCGAGG
	GCCTCTACTGGACCCTCAACGGGCGCCGCCTGCCCCCTGAGCTCTCCCGTGTACTCAACGCCTCCAC
	CTTGGCTCTGGCCCTGGCCAACCTCAATGGGTCCAGGCAGCGGTCGGGGGACAACCTCGTGTGCCAC
	GCCCGTGACGGCAGCATCCTGGCTGGCTCCTGCCTCTATGTTGGCCTGCCCCCAGAGAAACCCGTCA
	ACATCAGCTGCTGGTCCAAGAACATGAAGGACTTGACCTGCCGCTGGACGCCAGGGGCCCACGGGGA
	GACCTTCCTCCACACCAACTACTCCCTCAAGTACAAGCTTAGGTGGTATGGCCAGGACAACACATGT
	GAGGAGTACCACGGCGAGAGGTCCTGCCAGATAAGCTGTAGGGGCTCAGGCCACCCTCCCTGCCACG
	TGGAGACGCAGAGGCCGAACCCAAACTGGGGCCACCTCTGTACCCTCACTTCAGGGCACCTGAGCCA
	CCCTCAGCAGGAGCTGGGGTGGCCCCTGAGCTCCAACGGCCATAACAGCTCTGACTCCCACGTGAGG
	CCACCTTTGGGTGCACCCCAGTGGGTGTGTGTGTGTGTGTGAGGGTTGGTTGAGTTGCCTAGAACCC
	CTGCCAGGGCTGGGGGTGAGAAGGGGAGTCATTACTCCCCATTACCTAGGGCCCCTCCAAAAGAGTC
	CTTTTAAATAAATGAGCTATTTAGGTGC
	ORF Start: ATG at 119		ORF Stop: TGA at 911
	SEQ ID NO: 126	264 aa	MW at 28400.9 kD
NOV22a,	MPAGRRGPAAQSARRPPPLLPLLLLLCVLGAPRAGSGAHTAVISPQDPTLLIGSSLLATCSVHGDPP
CG163259-01
Protein Sequence	GATAEGLYWTLNGRRLPPELSRVLNASTLALALANLNGSRQRSGDNLVCHARDGSILAGSCLYVGLP
	PEKPVNISCWSKNMKDLTCRWTPGAHGETFLHTNYSLKYKLRWYGQDNTCEEYHGERSCQISCRGSG
	HPPCHVETQRPNPNWGHLCTLTSGHLSHPQQELGWPLSSNGHNSSDSHVRPPLGAPQWVCVCV
	SEQ ID NO: 127	1485 bp
NOV22b,	CGCCCAGCGACGTGCGGGCGGCCTGGCCCGCGCCCTCCCGCGCCCGGCCTGCGTCCCGCGCCCTGCG
CG163259-02
DNA Sequence	CCACCGCCGCCGAGCCGCAGCCCGCCGCGCGCCCCCGGCAGCGCCGGCCCCATGCCCGCCGGCCGCC
	GGGGCCCCGCCGCCCAATCCGCGCGGCGGCCGCCGCCGTTGCTGCCCCTGCTGCTGCTGCTCTGCGT
	CCTCGGGGCGCCGCGAGCCGGATCAGGAGCCCACACAGCTGTGATCAGTCCCCAGGATCCCACGCTT
	CTCATCGGCTCCTCCCTGCTGGCCACCTGCTCAGTGCACGGAGACCCACCAGGAGCCACCGCCGAGG
	GCCTCTACTGGACCCTCAACGGGCGCCGCCTGCCCCCTGAGCTCTCCCGTGTACTCAACGCCTCCAC
	CTTGGCTCTGGCCCTGGCCAACCTCAATGGGTCCAGGCAGCGGTCGGGGGACAACCTCGTGTGCCAC
	GCCCGTGACGGCAGCATCCTGGCTCTCTTTACGCCCTATGAGATCTGGGTGGAGGCCACCAACCGCC
	TGGGCTCTGCCCGCTCCGATGTACTCACGCTGGATATCCTGGATGTGGTGACCACGGACCCCCCGCC
	CGACGTGCACGTGAGCCGCGTCGGGGGCCTGGAGGACCAGCTGAGCGTGCGCTGGGTGTCGCCACCC
	GCCCTCAAGGATTTCCTCTTTCAAGCCAAATACCAGATCCGCTACCGAGTGGAGGACAGTGTGGACT
	GGAAGGTGGTGGACGATGTGAGCAACCAGACCTCCTGCCGCCTGGCCGGCCTGAAACCCGGCACCGT
	GTACTTCGTGCAAGTGCGCTGCAACCCCTTTGGCATCTATGGCTCCAAGAAAGCCGGGATCTGGAGT
	GAGTGGAGCCACCCCACAGCCGCCTCCACTCCCCGCAGTGAGCGCCCGGGCCCGGGCGGCGGGGCGT
	GCGAACCGCGGGGCGGAGAGCCGAGCTCGGGGCCGGTGCGGCGCGAGCTCAAGCAGTTCCTGGGCTG
	GCTCAAGAAGCACGCGTACTGCTCCAACCTCAGCTTCCGCCTCTACGACCAGTGGCGAGCCTGGATG
	CAGAAGTCGCACAAGACCCGCAACCAGGACGAGGGGATCCTGCCCTCGGGCAGACGGGGCACGGCGA
	GAGGTCCTGCCAGATAAGCTGTAGGGGCTCAGGCCACCCTCCCTGCCACGTGGAGACGCAGAGGCCG
	AACCCAAACTGGGGCCACCTCTGTACCCTCACTTCAGGGCACCTGAGCCACCCTCAGCAGGAGCTGG
	GGTGGCCCCTGAGCTCCAACGGCCATAACAGCTCTGACTCCCACGTGAGGCCACCTTTGGGTGCACC
	CCAGTGGGTGTGTGTGTGTGTGTGAGGGTTGGTTGAGTTGCCTAGAACCCCTGCCAGGGCTGGGGGT
	GAGAAGGGGAGTCATTACTCCCCATTACCTAGGGCCCCTCCAAAAGAGTCCTTTTAAATAAATGAGC
	TATTTAGGTGC
	ORF Start: ATG at 119		ORF Stop: TAA at 1154
	SEQ ID NO: 128	345 aa	MW at 37494.2 kD
NOV22b,	MPAGRRGPAAQSARRPPPLLPLLLLLCVLGAPRAGSGAHTAVISPQDPTLLIGSSLLATCSVHGDPP
CG163259-02
Protein Sequence	GATAEGLYWTLNGRRLPPELSRVLNASTLALALANLNGSRQRSGDNLVCHARDGSILALFTPYEIWV
	EATNRLGSARSDVLTLDILDVVTTDPPPDVHVSRVGGLEDQLSVRWVSPPALKDFLFQAKYQIRYRV
	EDSVDWKVVDDVSNQTSCRLAGLKPGTVYFVQVRCNPFGIYGSKKAGIWSEWSHPTAASTPRSERPG
	PGGGACEPRGGEPSSGPVRRELKQFLGWLKKHAYCSNLSFRLYDQWRAWMQKSHKTRNQDEGILPSG
	RRGTARGPAR
	SEQ ID NO: 129	814 bp
NOV22c,	CGCCCAGCGACGTGCGGGCGGCCTGGCCCGCGCCCTCCCGCGCCCGGCCTGCGTCCCGCGCCCTGCG
CG163259-03
DNA Sequence	CCACCGCCGCCGAGCCGCAGCCCGCCGCGCGCCCCCGGCAGCGCCGGCCCCATGCCCGCCGGCCGCC
	GGGGCCCCGCCGCCCAATCCGCGCGGCGGCCGCCGCCGTTGCTGCCCCTGCTGCTGCTGCTCTGCGT
	CCTCGGGGCGCCGCGAGCCGGATCAGGAGCCCACACAGCTGTGATCAGTCCCCAGGATCCCACGCTT
	CTCATCGGCTCCTCCCTGCTGGCCACCTGCTCAGTGCACGGAGACCCACCAGGAGCCACCGCCGAGG
	GCCTCTACTGGACCCTCAACGGGCGCCGCCTGCCCCCTGAGCTCTCCCGTGTACTCAACGCCTCCAC
	CTTGGCTCTGGCCCTGGCCAACCTCAATGGGTCCAGGCAGCGGTCGGGGGACAACCTCGGGCAGACG
	GGGCACGGCGAGAGGTCCTGCCAGATAAGCTGTAGGGGCTCAGGCCACCCTCCCTGCCACGTGGAGA
	CGCAGAGGCCGAACCCAAACTGGGGCCACCTCTGTACCCTCACTTCAGGGCACCTGAGCCACCCTCA
	GCAGGAGCTGGGGTGGCCCCTGAGCTCCAACGGCCATAACAGCTCTGACTCCCACGTGAGGCCACCT
	TTGGGTGCACCCCAGTGGGTGTGTGTGTGTGTGTGAGGGTTGGTTGAGTTGCCTAGAACCCCTGCCA
	GGGCTGGGGGTGAGAAGGGGAGTCATTACTCCCCATTACCTAGGGCCCCTCCAAAAGAGTCCTTTTA
	AATAAATGAG
	ORF Start: ATG at 119		ORF Stop: TGA at 704
	SEQ ID NO: 130	195 aa	MW at 20407.9 kD
NOV22c,	MPAGRRGPAAQSARRPPPLLPLLLLLCVLGAPRAGSGAHTAVISPQDPTLLIGSSLLATCSVHGDPP
CG163259-03
Protein Sequence	GATAEGLYWTLNGRRLPPELSRVLNASTLALALANLNGSRQRSGDNLGQTGHGERSCQISCRGSGHP
	PCHVETQRPNPNWGHLCTLTSGHLSHPQQELGWPLSSNGHNSSDSHVRPPLGAPQWVCVCV

[0487] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 22B.

TABLE 22B
Comparison of NOV22a against NOV22b and NOV22c.
	NOV22a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV22b	1 . . . 204	146/229 (63%)
	1 . . . 226	159/229 (68%)
NOV22c	1 . . . 135	119/135 (88%)
	1 . . . 135	119/135 (88%)

[0488] Further analysis of the NOV22a protein yielded the following properties shown in Table 22C.

TABLE 22C
Protein Sequence Properties NOV22a
SignalP
analysis:	Cleavage site between residues 38 and 39
PSORT II	PSG:	a new signal peptide prediction method
analysis:		N-region: length 6; pos. chg 2; neg. chg 0
		H-region: length 7; peak value −5.34
		PSG score: −9.74
	GvH:	von Heijne's method for signal seq. recognition
		GvH score (threshold: −2.1): 3.08
		possible cleavage site: between 30 and 31
	>>> Seems to have no N-terminal signal peptide
	ALOM:	Klein et al's method for TM region allocation
		Init position for calculation: 1
		Tentative number of TMS(s) for the threshold 0.5: 1
		Number of TMS(s) for threshold 0.5: 1
		INTEGRAL Likelihood = −2.81
		Transmembrane 19-35
		PERIPHERAL Likelihood = 3.45 (at 87)
		ALOM score: −2.81 (number of TMSs: 1)
	MTOP:	Prediction of membrane topology (Hartmann et al.)
		Center position for calculation: 26
		Charge difference: −4.5 C(0.5) − N(5.0)
		N >= C: N-terminal side will be inside
	>>> membrane topology: type 2 (cytoplasmic tail 1 to 19)
	MITDISC: discrimination of mitochondrial targeting seq
		R content: 5	Hyd Moment (75): 9.72
		Hyd Moment (95): 9.38	G content: 5
		D/E content: 1	S/T content: 4
		Score: −0.72
	Gavel:	prediction of cleavage sites for mitochondrial preseq
		R-2 motif at 43 PRA|GS
	NUCDISC: discrimination of nuclear localization signals
		pat4: none
		pat7: none
		bipartite: none
		content of basic residues: 8.3%
		NLS Score: −0.47
	KDEL:	ER retention motif in the C-terminus: none
	ER Membrane Retention Signals:
		XXRR-like motif in the N-terminus: PAGR
	none
	SKL: peroxisomal targeting signal in the C-terminus: none
	PTS2: 2nd peroxisomal targeting signal: none
	VAC: possible vacuolar targeting motif: none
	RNA-binding motif: none
	Actinin-type actin-binding motif:
		type 1: none
		type 2: none
	NMYR:	N-myristoylation pattern: none
	Prenylation motif: none
	memYQRL: transport motif from cell surface to Golgi: none
	Tyrosines in the tail: none
	Dileucine motif in the tail: none
	checking 63 PROSITE DNA binding motifs: none
	checking 71 PROSITE ribosomal protein motifs: none
	checking 33 PROSITE prokaryotic DNA binding motifs: none
	NNCN:	Reinhardt's method for Cytoplasmic/Nuclear
		discrimination
		Prediction: nuclear
		Reliability: 94.1
	COIL:	Lupas's algorithm to detect coiled-coil regions
		total: 0 residues
	----------------------------------
	Final Results (k = 9/23):
		39.1%: nuclear
		34.8%: mitochondrial
		8.7%: cytoplasmic
		4.3%: extracellular, including cell wall
		4.3%: Golgi
		4.3%: plasma membrane
		4.3%: peroxisomal
	>> prediction for CG163259-01 is nuc (k = 23)

[0489] 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 22D.

TABLE 22D
Geneseq Results for NOV22a
Geneseq	Protein/Organism/Length	NOV22a Residues/	Identities/Similarities	Expect
Identifier	[Patent #, Date]	Match Residues	for the Matched Region	Value
ABB06125	Human NS protein sequence	1 . . . 195	192/197 (97%)	e−112
	SEQ ID NO:217 - Homo	1 . . . 197	192/197 (97%)
	sapiens, 457 aa.
	[WO200206315-A2,
	24-JAN-2002]
AAB36647	Human cytokine receptor	1 . . . 195	192/197 (97%)	e−112
	subunit NR6 protein SEQ ID	1 . . . 197	192/197 (97%)
	NO:4 - Homo sapiens, 410
	aa. [WO200073451-A1,
	07-DEC-2000]
AAG63545	Amino acid sequence of a	1 . . . 195	192/197 (97%)	e−112
	human CLF-1 protein -	1 . . . 197	192/197 (97%)
	Homo sapiens, 422 aa.
	[WO200155172-A2,
	02-AUG-2001]
AAG63544	Amino acid sequence of a	1 . . . 195	192/197 (97%)	e−112
	human CLF-1 protein -	1 . . . 197	192/197 (97%)
	Homo sapiens, 445 aa.
	[WO200155172-A2,
	02-AUG-2001]
AAY44840	Human orphan cytokine	1 . . . 195	192/197 (97%)	e−112
	receptor-1 - Homo sapiens,	1 . . . 197	192/197 (97%)
	448 aa. [WO200005370-A1,
	03-FEB-2000]

[0490] 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 22E.

TABLE 22E
Public BLASTP Results for NOV22a
Protein		NOV22a Residues/	Identities/Similarities	Expect
Accession Number	Protein/Organism/Length	Match Residues	for the Matched Portion	Value
CAC60176	Sequence 3 from Patent	1 . . . 195	192/197 (97%)	e−111
	WO0155172 - Homo sapiens	1 . . . 197	192/197 (97%)
	(Human), 445 aa.
Q9UHH5	Class I cytokine receptor -	1 . . . 195	192/197 (97%)	e−111
	Homo sapiens (Human), 422	1 . . . 197	192/197 (97%)
	aa.
O75462	Cytokine-like factor-1	1 . . . 195	192/197 (97%)	e−111
	precursor - Homo sapiens	1 . . . 197	192/197 (97%)
	(Human), 422 aa.
Q9JM58	Cytokine receptor like	1 . . . 195	175/200 (87%)	3e−99
	molecule 3 precursor - Mus	1 . . . 200	179/200 (89%)
	musculus (Mouse), 425 aa.
CAB42575	SEQUENCE 18 FROM	48 . . . 195	136/150 (90%)	3e−78
	PATENT WO9811225 -	1 . . . 150	140/150 (92%)
	unidentified, 278 aa
	(fragment).

[0491] PFam analysis predicts that the NOV22a protein contains the domains shown in the Table 22F.

TABLE 22F
Domain Analysis of NOV22a
		Identities/
		Similarities
		for the Matched	Expect
Pfam Domain	NOV22a Match Region	Region	Value

Example 23

[0492] 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: 131	1375 bp
NOV23a,	CCCAGAGCAGCGCTCGCCACCTCCCCCCGGCCTGGGCAGCGCTCGCCCGGGGAGTCCAGCGGTGTCC
CG163425-01
DNA Sequence	TGTGGAGCTGCCGCCATGGCCCCGCGGCGGGCGCGCGGCTGCCGGACCCTCGGTCTCCCGGCGCTGC
	TACTGCTGCTGCTGCTCCGGCCGCCGGCGACGCGGGGCATCACGTGCCCTCCCCCCATGTCCGTGGA
	ACACGCAGACATCTGGGTCAAGAGCTACAGCTTGTACTCCAGGGAGCGGTACATTTGTAACTCTGGT
	TTCAAGCGTAAAGCCGGCACGTCCAGCCTGACGGAGTGCGTGTTGAACAAGGCCACGAATGTCGCCC
	ACTGGACAACCCCCAGTCTCAAATGCATTAGAACCACAGAGATAAGCAGTCATGAGTCCTCCCACGG
	CACCCCCTCTCAGACAACAGCCAAGAACTGGGAACTCACAGCATCCGCCTCCCACCAGCCGCCAGGT
	GTGTATCCACAGGGCCACAGCGACACCACTGTGGCTATCTCCACGTCCACTGTCCTGCTGTGTGGGC
	TGAGCGCTGTGTCTCTCCTGGCATGCTACCTCAAGTCAAGGCAAACTCCCCCGCTGGCCAGCGTTGA
	AATGGAAGCCATGGAGGCTCTGCCGGTGACTTGGGGGACCAGCAGCAGAGATGAAGACTTGGAAAAC
	TGCTCTCACCACCTATGAAACTCGGGGAAACCAGCCCAGCTAAGTCCGGAGTGAAGGAGCCTCTCTG
	CTTTAGCTAAAGACGACTGAGAAGAGGTGCAAGGAAGCGGGCTCCAGGAGCAAGCTCACCAGGCCTC
	TCAGAAGTCCCAGCAGGATCTCACGGACTGCCGGGTCGGCGCCTCCTGCGCGAGGGAGCAGGTTCTC
	CGCATTCCCATGGGCACCACCTGCCTGCCTGTCGTGCCTTGGACCCAGGGCCCAGCTTCCCAGGAGA
	GACCAAAGGCTTCTGAGCAGGATTTTTATTTCATTACAGTGTGAGCTGCCTGGAATACATGTGGTAA
	TGAAATAAAAACCCTGCCCCGAATCTTCCGTCCCTCATCCTAACTTTCAGTTCACAGAGAAAAGTGA
	CATACCCAAAGCTCTCTGTCAATTACAAGGCTTCTCCTGGCGTGGGAGACGTCTACAGGGAAGACAC
	CAGCGTTTGGGCTTCTAACCACCCTGTCTCCAGCTGCTCTGCACACATGGACAGGGACCTGGGAAAG
	GTGGGAGAGATGCTGAGCCCAGCGAATCCTCTCCATTGAAGGATTCAGGAAGAAGAAAACTCAACTC
	AGTGCCATTTTACGAATATATGCGTTTATATTTATACTTCCTTGTCTATTATATCTATACATTATAT
	ATTATTTGTATTTTGACATTGTACCTTGTATAAAC
	ORF Start: ATG at 83		ORF Stop: TGA at 686
	SEQ ID NO: 132	201 aa	MW at 21829.6 kD
NOV23a,	MAPRRARGCRTLGLPALLLLLLLRPPATRGITCPPPMSVEHADIWVKSYSLYSRERYICNSGFKRKA
CG163425-01
Protein Sequence	GTSSLTECVLNKATNVAHWTTPSLKCIRTTEISSHESSHGTPSQTTAKNWELTASASHQPPGVYPQG
	HSDTTVAISTSTVLLCGLSAVSLLACYLKSRQTPPLASVEMEAMEALPVTWGTSSRDEDLENCSHHL
	SEQ ID NO: 133	1474 bp
NOV23b,	CCCAGAGCAGCGCTCGCCACCTCCCCCCGGCCTGGGCAGCGCTCGCCCGGGGAGTCCAGCGGTGTCC
CG163425-02
DNA Sequence	TGTGGAGCTGCCGCCATGGCCCCGCGGCGGGCGCGCGGCTGCCGGACCCTCGGTCTCCCGGCGCTGC
	TACTGCTGCTGCTGCTCCGGCCGCCGGCGACGCGGGGCATCACGTGCCCTCCCCCCATGTCCGTGGA
	ACACGCAGACATCTGGGTCAAGAGCTACAGCTTGTACTCCAGGGAGCGGTACATTTGTAACTCTGGT
	TTCAAGCGTAAAGCCGGCACGTCCAGCCTGACGGAGTGCGTGTTGAACAAGGCCACGAATGTCGCCC
	ACTGGACAACCCCCAGTCTCAAATGCATTAAGCCCGCACCTTCATCTCCCAGCTCAAACAACACAGC
	GGCCACAACAGCAGCTATTGTCCCGGGCTCCCAGCTGATGCCTTCAAAATCACCTTCCACAGGAACC
	ACAGAGATAAGCAGTCATGAGTCCTCCCACGGCACCCCCTCTCAGACAACAGCCAAGAACTGGGAAC
	TCACAGCATCCGCCTCCCACCAGCCGCCAGGTGTGTATCCACAGGGCCACAGCGACACCACTGTGGC
	TATCTCCACGTCCACTGTCCTGCTGTGTGGGCTGAGCGCTGTGTCTCTCCTCGCATGCTACCTCAAG
	TCAAGGCAAACTCCCCCGCTGGCCAGCGTTGAAATGGAAGCCATGGAGGCTCTGCCGGTGACTTGGG
	GGACCAGCAGCAGAGATGAAGACTTGGAAAACTGCTCTCACCACCTATGAAACTCGGGGAAACCAGC
	CCAGCTAAGTCCGGAGTGAAGGAGCCTCTCTGCTTTAGCTAAAGACGACTGAGAAGAGGTGCAAGGA
	AGCGGGCTCCAGGAGCAAGCTCACCAGGCCTCTCAGAAGTCCCAGCAGGATCTCACGGACTGCCGGG
	TCGGCGCCTCCTGCGCGAGGGAGCAGGTTCTCCGCATTCCCATGGGCACCACCTGCCTGCCTGTCGT
	GCCTTGGACCCAGGGCCCAGCTTCCCAGGAGAGACCAAAGGCTTCTGAGCAGGATTTTTATTTCATT
	ACAGTGTGAGCTGCCTGGAATACATGTGGTAATGAAATAAAAACCCTGCCCCGAATCTTCCGTCCCT
	CATCCTAACTTTCAGTTCACAGAGAAAAGTGACATACCCAAAGCTCTCTGTCAATTACAAGGCTTCT
	CCTGGCGTGGGAGACGTCTACAGGGAAGACACCAGCGTTTGGGCTTCTAACCACCCTGTCTCCAGCT
	GCTCTGCACACATGGACAGGGACCTGGGAAAGGTGGGAGAGATGCTGAGCCCAGCGAATCCTCTCCA
	TTGAAGGATTCAGGAAGAAGAAAACTCAACTCAGTGCCATTTTACGAATATATGCGTTTATATTTAT
	ACTTCCTTGTCTATTATATCTATACATTATATATTATTTGTATTTTGACATTGTACCTTGTATAAAC
	ORF Start: ATG at 83		ORF Stop: TGA at 785
	SEQ ID NO: 134	234 aa	MW at 24869.9 kD
NOV23b,	MAPRRARGCRTLGLPALLLLLLLRPPATRGITCPPPMSVEHADIWVKSYSLYSRERYICNSGFKRKA
CG163425-02
Protein Sequence	GTSSLTECVLNKATNVAHWTTPSLKCIKPAASSPSSNNTAATTAAIVPGSQLMPSKSPSTGTTEISS
	HESSHGTPSQTTAKNWELTASASHQPPGVYPQGHSDTTVAISTSTVLLCGLSAVSLLACYLKSRQTP
	PLASVEMEAMEALPVTWGTSSRDEDLENCSHHL

[0493] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 23B.

TABLE 23B
Comparison of NOV23a against NOV23b.
	NOV23a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV23b	1 . . . 201	200/234 (85%)
	1 . . . 234	201/234 (85%)

[0494] Further analysis of the NOV23a protein yielded the following properties shown in Table 23C.

TABLE 23C
Protein Sequence Properties NOV23a
SignalP
analysis:	Cleavage site between residues 31 and 32
PSORT II	PSG:	a new signal peptide prediction method
analysis:		N-region: length 10; pos. chg 4; neg. chg 0
		H-region: length 13; peak value 11.07
		PSG score: 6.67
	GvH:	von Heijne's method for signal seq. recognition
		GvH score (threshold: −2.1): 4.42
		possible cleavage site: between 30 and 31
	>>> Seems to have a cleavable signal peptide (1 to 30)
	ALOM:	Klein et al's method for TM region allocation
		Init position for calculation: 31
		Tentative number of TMS(s) for the threshold 0.5: 1
		Number of TMS(s) for threshold 0.5: 1
		INTEGRAL Likelihood = −4.73
		Transmembrane 146-162
		PERIPHERAL Likelihood = 8.80 (at 170)
		ALOM score: −4.73 (number of TMSs: 1)
	MTOP:	Prediction of membrane topology (Hartmann et al.)
		Center position for calculation: 15
		Charge difference: −3.0 C(2.0) − N(5.0)
		N >= C: N-terminal side will be inside
	>>> membrane topology: type 1a (cytoplasmic tail 163
		to 201)
	MITDISC: discrimination of mitochondrial targeting seq
		R content: 6	Hyd Moment (75): 6.07
		Hyd Moment (95): 8.42	G content: 3
		D/E content: 1	S/T content: 4
		Score: 0.52
	Gavel:	prediction of cleavage sites for mitochondrial preseq
		R-2 motif at 39 TRG|IT
	NUCDISC: discrimination of nuclear localization signals
		pat4: none
		pat7: PRRARGC (5) at 3
		bipartite: none
		content of basic residues: 9.5%
		NLS Score: −0.04
	KDEL:	ER retention motif in the C-terminus: none
	ER Membrane Retention Signals:
		XXRR-like motif in the N-terminus: APRR
	none
	SKL: peroxisomal targeting signal in the C-terminus: none
	PTS2: 2nd peroxisomal targeting signal: none
	VAC: possible vacuolar targeting motif: none
	RNA-binding motif: none
	Actinin-type actin-binding motif:
		type 1: none
		type 2: none
	NMYR: N-myristoylation pattern: none
	Prenylation motif: none
	memYQRL: transport motif from cell surface to Golgi: none
	Tyrosines in the tail: none
	Dileucine motif in the tail: none
	checking 63 PROSITE DNA binding motifs: none
	checking 71 PROSITE ribosomal protein motifs: none
	checking 33 PROSITE prokaryotic DNA binding motifs: none
	NNCN:	Reinbardt's method for Cytoplasmic/Nuclear
		discrimination
		Prediction: nuclear
		Reliability: 94.1
	COIL:	Lupas's algorithm to detect coiled-coil regions
		total: 0 residues
	----------------------------------
	Final Results (k = 9/23):
		44.4%: extracellular, including cell wall
		22.2%: Golgi
		22.2%: endoplasmic reticulum
		11.1%: plasma membrane
	>> prediction for CG163425-01 is exc (k = 9)

[0495] 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 23D.

TABLE 23D
Geneseq Results for NOV23a
Geneseq	Protein/Organism/Length	NOV23a Residues/	Identities/Similarities	Expect
Identifier	[Patent #, Date]	Match Residues	for the Matched Region	Value
AAR90844	Human interleukin-15	1 . . . 201	200/234 (85%)	e−111
	receptor from clone A212 -	1 . . . 234	201/234 (85%)
	Homo sapiens, 234 aa.
	[WO9530695-A,
	16-NOV-1995]
AAR90843	Human interleukin-15	7 . . . 201	193/279 (69%)	1e−99
	receptor from clone P1 -	1 . . . 279	194/279 (69%)
	Homo sapiens, 279 aa.
	[WO9530695-A,
	16-NOV-1995]
AAR90847	Composite human	1 . . . 201	184/267 (68%)	4e−95
	interleukin-15 receptor -	1 . . . 267	189/267 (69%)
	Homo sapiens, 267 aa.
	[WO9530695-A,
	16-NOV-1995]
AAR91594	Human interleukin-15	17 . . . 201	171/251 (68%)	5e−87
	receptor - Homo sapiens, 251	1 . . . 251	175/251 (69%)
	aa. [WO9530695-A,
	16-NOV-1995]
AAR90846	Hybrid construct of IL-15R	28 . . . 165	124/204 (60%)	2e−58
	alternate cytoplasmic tail -	1 . . . 204	128/204 (61%)
	Homo sapiens, 225 aa.
	[W09530695-A,
	16-NOV-1995]

[0496] 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 23E.

TABLE 23E
Public BLASTP Results for NOV23a
Protein		NOV23a Residues/	Identities/Similarities	Expect
Accession Number	Protein/Organism/Length	Match Residues	for the Matched Portion	Value
Q13261	Interleukin-15 receptor alpha	1 . . . 201	188/267 (70%)	3e−97
	chain precursor - Homo	1 . . . 267	192/267 (71%)
	sapiens (Human), 267 aa.
Q9ESL1	Interleukin-15 receptor alpha	1 . . . 193	110/259 (42%)	2e−45
	chain precursor - Cavia	1 . . . 259	135/259 (51%)
	porcellus (Guinea pig), 268
	aa.
CAD10564	Sequence 85 from Patent	31 . . . 137	94/173 (54%)	3e−41
	WO0177171 - Homo sapiens	1 . . . 173	98/173 (56%)
	(Human), 173 aa (fragment).
Q60819	Interleukin 15 receptor	1 . . . 193	107/259 (41%)	2e−39
	precursor - Mus musculus	1 . . . 259	132/259 (50%)
	(Mouse), 263 aa.
Q8R5E4	Similar to interleukin 15	96 . . . 193	38/98 (38%)	4e−08
	receptor, alpha chain - Mus	23 . . . 119	53/98 (53%)
	musculus (Mouse), 123 aa.

[0497] PFam analysis predicts that the NOV23a protein contains the domains shown in the Table 23F.

TABLE 23F
Domain Analysis of NOV23a
		Identities/
		Similarities
		for the Matched	Expect
Pfam Domain	NOV23a Match Region	Region	Value

EAMPLE 24

[0498] 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: 135	5940 bp
NOV24a,	GCTCCAGCACTAGAGCCAGCTGCGAGCGGAGGGCACCAACTCCGCAGAACTGGCTTTTCAATGGGAC
CG163957-01
DNA Sequence	ACCTGTGGCTCCTGGGTATTTGGGGCCTCTGTGGGCTGCTCCTGTGTGCCGCGGATCCCAGCACAGA
	TGGCTCTCAAATAATCCCCAAAGTCACAGAAATAATACCTAAATATGGCAGTATAAATGGAGCAACA
	AGGCTGACTATAAGAGGGGAAGCTTTTTCTCAAGCAAACCAGTTTAACTATGGAGTTGATAACGCTG
	AGTTGGGAAACAGTGTGCAATTAATTTCTTCTTTCCAGTCAATTACTTGTGATGTAGAAAAAGATGC
	AAGTCATTCAACTCAAATTACATGCTATACTAGAGCAATGCCGGAAGATTCCTACACTGTTAGAGTC
	AGTGTGGACGGGGTTCCTGTTACGGAAAATAACACCTGCAAAGGTCACATCAACAGCTGGGAATGTA
	CCTTCAACGCAAAAAGTTTTAGAACCCCAACAATAAGAAGCATCACACCTTTATCTGGAACTCCAGG
	TACACTAATAACAATCCAAGGCAGAATCTTCACTGATGTCTATGGAAGTAATATTGCACTAAGCTCA
	AATGGGAAAAATGTTAGGATTTTGAGAGTTTACATTGGAGGAATGCCCTGTGAGCTTCTCATACCAC
	AATCTGATAATTTATATGGTCTAAAACTGGATCATCCAAATGGAGATATGGGTTCTATGGTTTGTAA
	GACGACTGGAACTTTTATTGGTCATCACAATGTCAGCTTCATCTTAGATAATGATTATGGAAGGAGT
	TTTCCACAGAAAATGGCATATTTTGTTTCTTCTCTCAATAAAATTGCAATGTTTCAAACATATGCAG
	AGGTCACCATGATTTTCCCTTCACAAGGAAGCATTCGAGGTGGCACCACGCTGACAATAAGTGGGCG
	TTTCTTTGATCAGACAGATTTCCCCGTCAGAGTTCTAGTTCGAGGTGAACCTTGTGATATTTTGAAT
	GTCACAGAAAATAGTATATGTTGCAAGACACCCCCCAAACCTCATATTCTCAAAACTGTATATCCAG
	GAGGGAGAGGCCTGAAGCTTGAGGTGTGGAATAATAGCCGTCCAATACGTTTGGAAGAGATACTGGA
	ATACAATGAAAAAACGCCTGGGTACATGGGTGCCAGTTGGGTAGATTCAGCTTCCTATATTTGGCTC
	ATGGAACAAGACACATTTGTTGCACGCTTTAGTGGATTTTTGGTGGCTCCAGATTCTGATGTTTATA
	GATTCTACATCAAGGGTGATGACCGTTATGCTATTTATTTTAGCCAGACTGGACTTCCAGAAGATAA
	GGTGAGGATTGCATATCATTCTGCTAATGCCAACAGTTATTTTTCCAGTCCAACACAAAGATCAGAT
	GATATTCATCTGCAGAAAGGAAAAGAATACTATATTGAAATCTTGCTGCAGGAGTACAGATTAAGTG
	CATTTGTTGATGTTGGACTGTACCAGTATCGAAATGTTTATACTGAACAACAAACAGGAGATGCAGT
	GAATGAAGAACAAGTTATCAAATCCCAGTCGACAATCCTCCAGGAAGTACAGGTTATAACATTGGAA
	AACTGGGAAACAACTAATGCAATTAATGAGGTTCAGAAGATCAAGGTAACCAGCCCATGTGTGGAAG
	CTAATTCATGTTCACTTTACCAATATAGATTAATCTATAATATGGAAAAAACTGTCTTCCTACCTGC
	TGATGCTTCTGAATTCATACTGCAATCAGCCTTGAATGACCTCTGGTCTATAAAACCGGACACAGTT
	CAAGTAATAAGAACACAAAATCCCCAGAGCTATGTCTACATGGTAACATTCATATCAACTAGAGGAG
	ACTTTGATCTGCTTGGTTATGAAGTAGTTGAAGGGAATAATGTCACACTGGATATTACAGAACAAAC
	CAAAGGAAAACCCAACTTGGAGACATTCACACTGAATTGGGATGGGATCGCTTCTAAGCCACTCACT
	CTATGGTCATCAGAAGCTGAATTTCAGGGAGCAGTGGAAGAAATGGTTAGCACTAAGTGTCCACCAC
	AAATTGCAAATTTTGAAGAAGGATTTGTTGTGAAATATTTCAGAGACTATGAAACTGATTTTAATCT
	GGAACATATTAACAGAGGGCAGAAGACAGCTGAAACCGATGCTTACTGTGGTCGTTATTCCCTGAAA
	AACCCACCTGTTCTTTTTGACTCAGCAGATGTTAAACCAAACAGACGACCATATGGAGATATTTTAT
	TGTTTCCTTATAATCAGTTATGTTTAGCATACAAAGGATTCCTGGCAAATTATATTGGTCTAAAATT
	TCAGTACCAAGACAATAGCAAGATTACTAGAAGCACTGATACACAGTTTACATACAACTTTGCTTAT
	GGAAACAACTGGACTTACACTTGCATAGACCTTCTGGATCTCGTAAGAACGAAATACACTGGGACAA
	ATGTTTCTCTTCAGAGGATTAGCTTACATAAAGCATCAGAATCACAGTCCTTCTATGTGGATGTAGT
	GTACATTGGACACACATCTACAATCTCAACATTGGATGAAATGCCCAAGAGAAGACTTCCTGCATTA
	GCAAATAAAGGAATATTCTTAGAGCACTTTCAGGTGAATCAGACCAAAACAAATGGGCCAACTATGA
	CAAACCAATATTCTGTTACCATGACTTCATACAATTGCAGTTACAATATACCCATGATGGCTGTGAG
	CTTTGGGCAGATAATCACACATGAGACAGAGAACGAGTTTGTCTACAGAGGAAATAATTGGCCAGGC
	GAGTCAAAAATTCATATTCAAAGAATTCAAGCTGCATCTCCACCTCTAAGTGGCAGCTTTGACATTC
	AAGCTTATGGACATATTCTTAAAGGCCTCCCCGCTGCTGTGTCAGCTGCAGATCTGCAGTTTGCACT
	CCAGAGTCTGGAGGGAATGGGAAGAATCTCAGTTACACGAGAGGGAACCTGTGCTGGCTACGCGTGG
	AACATCAAATGGAGAAGCACCTGCCGAAAGCAGAATCTTCTACAGATTAATGATTCCAACATTATTG
	GAGAAAAGGCTAATATGACAGTTACAAGGATAAAGGAAGGTGGCTTATTCAGACAACATGTACTTGG
	AGACCTACTTCGTACACCCAGTCAACAGCCACAGGTTGAAGTCTATGTCAATGGAATTCCAGCTAAA
	TGTTCAGGTGACTGTGGATTTACATGGGATTCCAACATTACTCCCCTAGTCTTGGCGATAAGCCCTT
	CTCAAGGGTCCTATGAAGAAGGCACAATTCTAACCATAGTGGGTTCTGGATTTTCTCCTAGTTCAGC
	TGTAACAGTCTCAGTTGGACCAGTAGGTTGTTCTCTTCTTTCTGTGGATGAAAAAGAGCTCAAGTGC
	CAGATTCTGAATGGAAGTGCTGGACATGCCCCCGTTGCTGTGTCCATGGCTGATGTTGGACTAGCAC
	AGAATGTAGGGGGTGAAGAGTTCTACTTTGTTTATCAGAGTCAGATCTCACATATCTGGCCTGATTC
	TGGAAGCATAGCAGGTGGTACTCTACTGACTTTATCTGGATTTGGCTTTAATGAAAATTCAAAGGTA
	TTAGTTGGAAATGAAACCTGCAATGTGATTGAAGGGGATTTGAATAGGATAACCTGCAGGACACCAA
	AAAAAACTGAGGGTACAGTTGATATTTCAGTTACTACCAATGGATTTCAAGCCACAGCAAGGGATGC
	TTTTAGTTATAATTGTTTACAGACACCAATTATAACTGATTTTAGTCCAAAAGTACGAACAATACTA
	GGAGAAGTTAATTTAACAATTAAGGGCTATAATTTTGGAAATGAACTCACACAAAACATGGCGGTGT
	ATGTTGGAGGAAAAACCTGCCAGATTCTTCACTGGAACTTCACAGATATTAGATGCCTTTTGCCCAA
	GTTGTCTCCTGGAAAACATGATATCTATGTAGAAGTCAGAAACTGGGGTTTTGCATCAACAAGAGAC
	AAATTAAATTCTTCAATACAGTATGTTTTAGAAGTGACCAGCATGTTTCCACAAAGAGGCTCCTTGT
	TTGGTGGAACTGAAATCACCATAAGGGGTTTTGGATTCAGCACAATACCAGCTGAGAATACCGTGCT
	GTTAGGGTCCATCCCTTGCAATGTTACATCATCATCAGAAAATGTCATAAAATGTATTCTTCATTCA
	ACTGGGAATATATTCAGGATTACCAACAATGGGAAAGATTCAGTACATGGATTAGGTTATGCCTGGT
	CACCACCAGTCCTAAATGTGTCTGTGGGGGACACAGTGGCATGGCATTGGCAAACACATCCGTTTCT
	TAGAGGGATAGGATATAGGATTTTTTCTGTCTCCAGTCCTGGAAGTGTAATTTATGATGGCAAAGGA
	TTCACAAGTGGAAGACAAAAATCTACATCAGGTTCATTTTCTTACCAATTTACTTCTCCTGGAATCC
	ATTATTATAGCAGCGGGTATGTTGATGAGGCTCACTCCATTTTTCTCCAAGGAGTCATTAATGTTTT
	ACCAGCTGAAACCAGACACATTCCCTTGCACCTGTTTGTGGGTCGCTCTGAAGCCACATATGCTTAT
	GGAGGACCTGAGAATTTGCACTTGGGAAGCTCTGTGGCAGGCTGCCTAGCAACAGAACCCCTGTGCA
	GCCTGAACAATACCAGGGTTAAAAATTCAAAAAGATTGCTATTTGAGGTTTCAAGTTGTTTTTCACC
	ATCTATAAGCAACATTACTCCGTCCACTGGAACAGTAAATGAACTAATAACAATTATTGGACATGGC
	TTTAGTAATCTCCCATGGGCTAATAAGGTTACAATTGGTAGCTACCCCTGTGTCGTAGAAGAAAGTA
	GTGAGGATTCAATTACATGTCATATTGACCCTCAAAACTCAATGGATGTTGGTATCAGGGAAACTGT
	CACTTTGACTGTCTACAACCTGGGCACTGCTATCAATACGTTGTCCAATGAATTTGATAGGCGATTT
	GTACTTTTGCCAAACATTGACCTGGTGTTGCCAAATGCAGGATCAACTACAGGAATGACAAGCGTGA
	CCATAAAAGGCTCTGGATTTGCCGTTTCTTCTGCAGGTGTAAAAGTCCTTATGGGTCATTTCCCATG
	TAAAGTTCTATCAGTGAATTATACGGCCATTGAATGTGAAACATCCCCTGCTGCCCAACAGCTTGTG
	GATGTAGATCTTCTAATACATGGAGTGCCTGCCCAGTGCCAGGGAAACTGCACCTTTTCATACTTAG
	AAAGCATCACTCCTTACATAACAGGAGTCTTCCCAAACTCTGTCATAGGATCTGTAAAAGTTCTTAT
	TGAAGGAGAAGGTTTGGGGACTGTTTTGGAGGACATTGCTGTTTTCATTGGAAATCAACAGTTCAGA
	GCAATAGAGGTTAATGAAAACAACATCACTGCTCTTGTGACTCCTCTCCCAGTTGGACATCATTCTG
	TTAGTGTTGTGGTGGGAAGTAAAGGCTTGGCTCTGGGAAACCTGACTGTCAGCAGCCCCCCAGTAGC
	ATCTCTATCACCAACTTCTGGAAGCATTGGTGGTGGAACTACACTGGTGATCACAGGAAATGGCTTC
	TATCCAGGCAACACTACAGTCACTATTGGGGATGAACCTTGTCAAATTATTTCCATCAACCCCAATG
	AAGTCTACTGCCGCACTCCCGCTGGGACCACTGGAATGGTCGATGTTAAAATCTTTGTTAATACAAT
	TGCTTATCCACCTTTGCTTTTTACATATGCCCTGGAGGATACTCCATTTCTCAGAGGAATTATCCCA
	AGCAGAGGTACTCCAATATCTGCCTTATTATCTTGATATTATAGTATCGATAATATTTATTAGTATG
	GAATTGGAATGATATTTGTAAATAACTATTAAGGTGTGTTTATA
	ORF Start: ATG at 61		ORF Stop: TGA at 5863
	SEQ ID NO: 136	1934 aa	MW at 211824.6 kD
NOV24a,	MGHLWLLGIWGLCGLLLCAADPSTDGSQIIPKVTEIIPKYGSINGATRLTIRGEGFSQANQFNYGVD
CG163957-01
Protein Sequence	NAELGNSVQLISSFQSITCDVEKDASHSTQITCYTRAMPEDSYTVRVSVDGVPVTENNTCKGHINSW
	ECTFNAKSFRTPTIRSITPLSGTPGTLITIQGRIFTDVYGSNIALSSNGKNVRILRVYIGGMPCELL
	IPQSDNLYGLKLDHPNGDMGSMVCKTTGTFIGHHNVSFILDNDYGRSFPQKMAYFVSSLNKIAMFQT
	YAEVTMIFPSQGSIRGGTTLTISGRFFDQTDFPVRVLVGGEPCDILNVTENSICCKTPPKPHILKTV
	YPGGRGLKLEVWNNSRPIRLEEILEYNEKTPGYMGASWVDSASYIWLMEQDTFVARFSGFLVAPDSD
	VYRFYIKGDDRYAIYFSQTGLPEDKVRIAYHSANANSYFSSPTQRSDDIHLQKGKEYYIEILLQEYR
	LSAFVDVGLYQYRNVYTEQQTGDAVNEEQVIKSQSTILQEVQVITLENWETTNAINEVQKIKVTSPC
	VEANSCSLYQYRLIYNMEKTVFLPADASEFILQSALNDLWSIKPDTVQVIRTQNPQSYVYMVTFIST
	RGDFDLLGYEVVEGNNVTLDITEQTKGKPNLETFTLNWDGIASKPLTLWSSEAEFQGAVEEMVSTKC
	PPQIANFEEGFVVKYFRDYETDFNLEHINRGQKTAETDAYCGRYSLKNPAVLFDSADVKPNRRPYGD
	ILLFPYNQLCLAYKGFLANYIGLKFQYQDNSKITRSTDTQFTYNFAYGNNWTYTCIDLLDLVRTKYT
	GTNVSLQRISLHKASESQSFYVDVVYIGHTSTISTLDEMPKRRLPALANKGIFLEHFQVNQTKTNGP
	TMTNQYSVTMTSYNCSYNIPMMAVSFGQIITHETENEFVYRGNNWPGESKIHIQRIQAASPPLSGSF
	DIQAYGHILKGLPAAVSAADLQFALQSLEGMGRISVTREGTCAGYAWNIKWRSTCGKQNLLQINDSN
	IIGEKANMTVTRIKEGGLFRQHVLGDLLRTPSQQPQVEVYVNGIPAKCSGDCGFTWDSNITPLVLAI
	SPSQGSYEEGTILTIVGSGFSPSSAVTVSVGPVGCSLLSVDEKELKCQILNGSAGHAPVAVSMADVG
	LAQNVGGEEFYFVYQSQISHIWPDSGSIAGGTLLTLSGFGFNENSKVLVGNETCNVIEGDLNRITCR
	TPKKTEGTVDISVTTNGFQATARDAFSYNCLQTPIITDFSPKVRTILGEVNLTIKGYNFGNELTQNM
	AVYVGGKTCQILHWNFTDIRCLLPKLSPGKHDIYVEVRNWGFASTRDKLNSSIQYVLEVTSMFPQRG
	SLFGGTEITIRGFGFSTIPAENTVLLGSIPCNVTSSSENVIKCILHSTGNIFRITNNGKDSVHGLGY
	AWSPPVLNVSVGDTVAWHWQTHPFLRGIGYRIFSVSSPGSVIYDGKGFTSGRQKSTSGSFSYQFTSP
	GIHYYSSGYVDEAHSIFLQGVINVLPAETRHIPLHLFVGRSEATYAYGGPENLHLGSSVAGCLATEP
	LCSLNNTRVKNSKRLLFEVSSCFSPSISNITPSTGTVNELITIIGHGFSNLPWANKVTIGSYPCVVE
	ESSEDSITCHIDPQNSMDVGIRETVTLTVYNLGTAINTLSNEFDRRFVLLPNIDLVLPNAGSTTGMT
	SVTIKGSGFAVSSAGVKVLMGHFPCKVLSVNYTAIECETSPAAQQLVDVDLLIHGVPAQCQGNCTFS
	YLESITPYITGVFPNSVIGSVKVLIEGEGLGTVLEDIAVFIGNQQFRAIEVNENNITALVTPLPVGH
	HSVSVVVGSKGLALGNLTVSSPPVASLSPTSGSIGGGTTLVITGNGFYPGNTTVTIGDEPCQIISIN
	PNEVYCRTPAGTTGMVDVKIFVNTIAYPPLLFTYALEDTPFLRGIIPSRGTPISALLS

[0499] Further analysis of the NOV24a protein yielded the following properties shown in Table 24B.

TABLE 24B
Protein Sequence Properties NOV24a
SignalP	Cleavage site between residues 21 and 22
analysis:
PSORT II	PSG: a new signal peptide prediction method
analysis:	N-region: length 0; pos.chg 0; neg.chg 0
	H-region: length 20; peak value 9.31
	PSG score: 4.91
	GvH: von Heijne's method for signal seq. recognition
	GvH score (threshold: −2.1): −1.16
	possible cleavage site: between 20 and 21
	>>> Seems to have a cleavable signal peptide (1 to 20)
	ALOM: Klein et al's method for TM region allocation
	Init position for calculation: 21
	Tentative number of TMS(s) for the threshold 0.5: 1
	Number of TMS(s) for threshold 0.5: 0
	PERIPHERAL Likelihood = 1.11 (at 1751)
	ALOM score: 0.16 (number of TMSs: 0)
	MTOP: Prediction of membrane topology (Hartmann et al.)
	Center position for calculation: 10
	Charge difference: −3.5 C(−2.0) − N(1.5)
	N >= C: N-terminal side will be inside
	MITDISC: discrimination of mitochondrial targeting seq
	R content:	0	Hyd Moment(75):	3.65
	Hyd Moment(95):	3.01	G content:	4
	D/E content:	1	S/T content:	0
	Score:	−7.61
	Gavel: prediction of cleavage sites for mitochondrial preseq
	cleavage site motif not found
	NUCDISC: discrimination of nuclear localization signals
	pat4: PKRR (4) at 844
	pat7: PKRRLPA (5) at 844
	bipartite: none
	content of basic residues: 7.2%
	NLS Score: 0.21
	KDEL: ER retention motif in the C-terminus: none
	ER Membrane Retention Signals: none
	SKL: peroxisomal targeting signal in the C-terminus: none
	PTS2: 2nd peroxisomal targeting signal: none
	VAC: possible vacuolar targeting motif: none
	RNA-binding motif: none
	Actinin-type actin-binding motif:
	type 1: none
	type 2: none
	NMYR: N-myristoylation pattern: none
	Prenylation motif: none
	memYQRL: transport motif from cell surface to Golgi: none
	Tyrosines in the tail: none
	Dileucine motif in the tail: none
	checking 63 PROSITE DNA binding motifs: none
	checking 71 PROSITE ribosomal protein motifs: none
	checking 33 PROSITE prokaryotic DNA binding motifs: none
	NNCN: Reinhardt's method for Cytoplasmic/Nuclear
	discrimination
	Prediction: cytoplasmic
	Reliability: 89
	COIL: Lupas's algorithm to detect coiled-coil regions
	total: 0 residues
Final Results (k = 9/23):
30.4%: cytoplasmic
30.4%: nuclear
8.7%: extracellular, including cell wall
8.7%: vacuolar
8.7%: mitochondrial
8.7%: endoplasmic reticulum
4.3%: vesicles of secretory system
>> prediction for CG163957-01 is cyt (k = 23)

[0500] 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
ABG37531	Human peptide encoded by	1598 . . . 1925	328/328 (100%)	0.0
	genome-derived single exon	1 . . . 328	328/328 (100%)
	probe SEQ ID 27196 -
	Homo sapiens, 328 aa.
	[WO200186003-A2,
	15-NOV-2001]
AAM03553	Peptide #2235 encoded by	1598 . . . 1925	328/328 (100%)	0.0
	probe for measuring breast	1 . . . 328	328/328 (100%)
	gene expression - Homo
	sapiens, 328 aa.
	[WO200157270-A2,
	09-AUG-2001]
AAM28325	Peptide #2362 encoded by	1598 . . . 1925	328/328 (100%)	0.0
	probe for measuring	1 . . . 328	328/328 (100%)
	placental gene expression -
	Homo sapiens, 328 aa.
	[WO200157272-A2,
	09-AUG-2001]
AAM15815	Peptide #2249 encoded by	1598 . . . 1925	328/328 (100%)	0.0
	probe for measuring cervical	1 . . . 328	328/328 (100%)
	gene expression - Homo
	sapiens, 328 aa.
	[WO200157278-A2,
	09-AUG-2001]
AAM67998	Human bone marrow	1598 . . . 1925	328/328 (100%)	0.0
	expressed probe encoded	1 . . . 328	328/328 (100%)
	protein SEQ ID NO: 28304 -
	Homo sapiens, 328 aa.
	09-AUG-2001]

[0501] 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
Protein		Residues/	Identities/
Accession		Match	Similarities for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
Q99PS9	D86 protein - Mus musculus	1 . . . 1933	1528/1933 (79%)	0.0
	(Mouse), 1944 aa.	1 . . . 1932	1699/1933 (87%)
AAM93492	Polycystic kidney and	637 . . . 1895	319/1323 (24%)	3e−67
	hepatic disease 1 - Homo	514 . . . 1717	536/1323 (40%)
	sapiens (Human), 4074 aa.
Q8TCZ9	Polycystic kidney and	637 . . . 1895	319/1323 (24%)	3e−67
	hepatic disease 1 precursor	514 . . . 1717	536/1323 (40%)
	(Fibrocystin) (Polyductin)
	(Tigmin) - Homo sapiens
	(Human), 4074 aa.
AAN05018	Polyductin - Mus musculus	630 . . . 1885	308/1315 (23%)	3e−66
	(Mouse), 4059 aa.	508 . . . 1703	546/1315 (41%)
Q8RD81	Hypothetical protein	1062 . . . 1355	88/317 (27%)	9e−15
	TTE0165 -	798 . . . 1105	143/317 (44%)
	Thermoanaerobacter
	tengcongensis, 1754 aa.

[0502] PFam analysis predicts that the NOV24a protein contains the domains shown in the Table 24E.

TABLE 24E
Domain Analysis of NOV24a
		Identities/
		Similarities for the	Expect
Pfam Domain	NOV24a Match Region	Matched Region	Value
TIG	31 . . . 130	26/120 (22%)	1.2e−05
		74/120 (62%)
TIG	146 . . . 256	28/122 (23%)	0.0019
		77/122 (63%)
TIG	270 . . . 362	26/111 (23%)	1.5e−11
		72/111 (65%)
TIG	1067 . . . 1152	26/104 (25%)	1.8e−08
		60/104 (58%)
TIG	1155 . . . 1235	27/104 (26%)	4.1e−13
		61/104 (59%)
TIG	1240 . . . 1323	21/105 (20%)	0.0076
		61/105 (58%)
TIG	1330 . . . 1470	29/153 (19%)	4.9e−07
		95/153 (62%)
TIG	1566 . . . 1650	23/106 (22%)	0.064
		61/106 (58%)
TIG	1659 . . . 1744	28/104 (27%)	2.3e−11
		65/104 (62%)
TIG	1749 . . . 1829	21/106 (20%)	0.00062
		58/106 (55%)
TIG	1831 . . . 1911	29/104 (28%)	2.4e−12
		63/104 (61%)

Example 25

[0503] 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: 137	1145 bp
NOV25a,	TGTGTTTTAGGTTCAGCCGTCTGTATATCTCCCCAGATACCTGAAACTGACCACCTGAGTACGTTTT
CG164482-01
DNA Sequence	CCCATTGCTGAGCTGTTTCCCTGATATCTGGCCATGCAACGGAGATCAAGAGGGATAAATACTGGAC
	TTATTCTACTCCTTTCTCAAATCTTCCATGTTGGGATCAACAATATTCCACCTGTCACCCTAGCAAC
	TTTGGCCCTCAACATCTGGTTCTTCTTGAACCCTCAGAAGCCACTGTATAGCTCCTGCCTTAGTGTG
	GAGAAGTGTTACCAGCAAAAAGACTGGCAGCGTTTACTGCTCTCTCCCCTTCACCATGCTGATGATT
	GGCATTTGTATTTCAATATGGCATCCATGCTCTGGAAAGGAATAAATCTAGAAAGAAGACTGGGAAG
	TAGATGGTTTGCCTATGTTATCACCGCATTTTCTGTACTTACTGGAGTGGTATACCTGCTCTTGCAA
	TTTGCTGTTGCCGAATTTATGGATGAACCTGACTTCAAAAGGAGCTGTGCTGTAGGTTTCTCAGGAG
	TTTTGTTTGCTTTGAAAGTTCTTAACAACCATTATTGCCCTGGAGGCTTTGTCAACATTTTGGGCTT
	TCCTGTACCGAACAGATTTGCTTGTTGGGTCGAACTTGTGGCTATTCATTTATTCTCACCACCTAGG
	ACTTCCTTCGCTGGGCATCTGGCTGGGATTCTTGTTGGACTAATGTACACTCAAGGGCCTCTGAAGA
	AAATCATGGAAGCATGTGCAGGTGGTTTTTCCTCCAGTGTTGGTTACCCAGGACGGCAATACTACTT
	TAATAGTTCAGGTAGCTCTGGATATCAGGATTATTATCCGCATGGCAGGCCAGATCACTATGAAGAA
	GCACCCAGGAACTATGACACGTACACAGCAGGACTGAGTGAAGAAGAACAGCTCGAGAGAGCATTAC
	AAGCCAGCCTCTGGGACGGAAATACCAGAAATAGCCCACCACCCTACGGGTTTCATCTCTCACCAGA
	AGAAATGAGGAGACAGCGGCTTCACAGATTCGATAGCCAGTGAGGTGGCATCTTGGGAAGACATGGC
	CTATTCGTGTAATTATTGCCCATTTGGCTCATTCCCCAAGCCCCTAATTCATTTTAATTCATTTTAA
	ACAAAA
	ORF Start: ATG at 101		ORF Stop: TGA at 1046
	SEQ ID NO: 138	315 aa	MW at 35862.7 kD
NOV25a,	MQRRSRGINTGLILLLSQIFHVGINNIPPVTLATLALNIWFFLNPQKPLYSSCLSVEKCYQQKDWQR
CG164482-01
Protein Sequence	LLLSPLHHADDWHLYFNMASMLWKGINLERRLGSRWFAYVITAFSVLTGVVYLLLQFAVAEFMDEPD
	FKRSCAVGFSGVLFALKVLNNHYCPGGFVNILGFPVPNRFACWVELVAIHLFSPPRTSFAGHLAGIL
	VGLMYTQGPLKKIMEACAGGFSSSVGYPGRQYYFNSSGSSGYQDYYPHGRPDHYEEAPRNYDTYTAG
	LSEEEQLERALQASLWDGNTRNSPPPYGFHLSPEEMRRQRLHRFDSQ

[0504] Further analysis of the NOV25a protein yielded the following properties shown in Table 25B.

TABLE 25B
Protein Sequence Properties NOV25a
SignalP	Cleavage site between residues 24 and 25
analysis:
PSORT II	PSG: a new signal peptide prediction method
analysis:	N-region: length 6; pos.chg 3; neg.chg 0
	H-region: length 40; peak value 8.94
	PSG score: 4.54
	GvH: von Heijne's method for signal seq. recognition
	GvH score (threshold: −2.1): −6.06
	possible cleavage site: between 61 and 62
	>>> Seems to have no N-terminal signal peptide
	ALOM: Klein et al's method for TM region allocation
	Init position for calculation: 1
	Tentative number of TMS(s) for the threshold 0.5: 3
	Number of TMS(s) for threshold 0.5: 1
	INTEGRAL Likelihood = −4.78 Transmembrane 106-122
	PERIPHERAL Likelihood = 0.53 (at 138)
	ALOM score: −4.78 (number of TMSs: 1)
	MTOP: Prediction of membrane topology (Hartmann et al.)
	Center position for calculation: 113
	Charge difference: −5.0 C(−2.0) − N(3.0)
	N >= C: N-terminal side will be inside
	>>> membrane topology: type 2 (cytoplasmic tail 1 to 106)
	MITDISC: discrimination of mitochondrial targeting seq
	R content:	3	Hyd Moment(75):	4.10
	Hyd Moment(95):	10.35	G content:	3
	D/E content:	1	S/T content:	8
	Score:	−1.05
	Gavel: prediction of cleavage sites for mitochondrial preseq
	R-2 motif at 16 SRG|IN
	NUCDISC: discrimination of nuclear localization signals
	pat4: none
	pat7: none
	bipartite: none
	content of basic residues: 8.6%
	NLS Score: −0.47
	KDEL: ER retention motif in the C-terminus: none
	ER Membrane Retention Signals:
	XXRR-like motif in the N-terminus: QRRS
	none
	SKL: peroxisomal targeting signal in the C-terminus: none
	PTS2: 2nd peroxisomal targeting signal: none
	VAC: possible vacuolar targeting motif: none
	RNA-binding motif: none
	Actinin-type actin-binding motif:
	type 1: none
	type 2: none
	NMYR: N-myristoylation pattern : none
	Prenylation motif: none
	memYQRL: transport motif from cell surface to Golgi: none
	Tyrosines in the tail: too long tail
	Dileucine motif in the tail: found
	LL at 14
	LL at 15
	checking 63 PROSITE DNA binding motifs: none
	checking 71 PROSITE ribosomal protein motifs: none
	checking 33 PROSITE prokaryotic DNA binding motifs: none
	NNCN: Reinhardt's method for Cytoplasmic/Nuclear
	discrimination
	Prediction: cytoplasmic
	Reliability: 94.1
	COIL: Lupas's algorithm to detect coiled-coil regions
	total: 0 residues
Final Results (k = 9/23):
43.5%: mitochondrial
21.7%: cytoplasmic
13.0%: Golgi
4.3%: vacuolar
4.3%: extracellular, including cell wall
4.3%: vesicles of secretory system
4.3%: nuclear
4.3%: endoplasmic reticulum
>> prediction for CG164482-01 is mit (k = 23)

[0505] 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
		Residues/	Identities/
Geneseq	Protein/Organism/Length	Match	Similarities for the	Expect
Identifier	[Patent #, Date]	Residues	Matched Region	Value
AAE17492	Human secretion and	1 . . . 315	313/316 (99%)	0.0
	trafficking protein-1 (SAT-1) -	1 . . . 315	313/316 (99%)
	Homo sapiens, 315 aa.
	[WO200202610-A2,
	10-JAN-2002]
ABG27447	Novel human diagnostic	1 . . . 144	144/144 (100%)	2e−81
	protein #27438 - Homo	4 . . . 147	144/144 (100%)
	sapiens, 236 aa.
	[WO200175067-A2,
	11-OCT-2001]
ABG14559	Novel human diagnostic	171 . . . 315	139/146 (95%)	3e−76
	protein #14550 - Homo	1 . . . 145	139/146 (95%)
	sapiens, 145 aa.
	[WO200175067-A2,
	11-OCT-2001]
ABG01637	Novel human diagnostic	1 . . . 119	119/119 (100%)	2e−66
	protein #1628 - Homo	1 . . . 119	119/119 (100%)
	sapiens, 119 aa.
	[WO200175067-A2,
	11-OCT-2001]
ABG02478	Novel human diagnostic	215 . . . 314	100/101 (99%)	2e−55
	protein #2469 - Homo	1 . . . 101	100/101 (99%)
	sapiens, 102 aa.
	[WO200175067-A2,
	11-OCT-2001]

[0506] 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
Q8TEB9	Hypothetical protein	1 . . . 315	313/316 (99%)	0.0
	FLJ23678 - Homo sapiens	1 . . . 315	313/316 (99%)
	(Human), 315 aa.
Q99K13	Similar to RIKEN cDNA	1 . . . 315	255/316 (80%)	e−152
	4930418P06 gene - Mus	1 . . . 315	278/316 (87%)
	musculus (Mouse), 315 aa.
Q9D5L8	4930418P06Rik protein -	1 . . . 315	253/316 (80%)	e−151
	Mus musculus (Mouse), 315	1 . . . 315	277/316 (87%)
	aa.
Q95LN6	Hypothetical 29.3 kDa	1 . . . 250	235/250 (94%)	e−138
	protein - Macaca fascicularis	1 . . . 249	243/250 (97%)
	(Crab eating macaque)
	(Cynomolgus monkey), 261
	aa.
AAH27900	Hypothetical protein	220 . . . 315	96/97 (98%)	2e−52
	DKFZp547E052 -	10 . . . 106	96/97 (98%)
	Homo sapiens (Human), 106 aa.

[0507] PFam analysis predicts that the NOV25a protein contains the domains shown in the Table 25E.

TABLE 25E
Domain Analysis of NOV25a
		Identities/
	NOV25a	Similarities for the
Pfam Domain	Match Region	Matched Region	Expect Value
Rhomboid	59 . . . 215	44/169 (26%)	7.4e−05
		102/169 (60%)
UIM	269 . . . 286	9/18 (50%)	0.42
		16/18 (89%)

Example 26

[0508] 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: 139	853 bp
NOV26a,	AGCCAACTTTCCTTTCAAATACACACCCCAACCCGCCCCGGCATACACAGAAATGGGGACTGCGAGC
CG164511-01
DNA Sequence	AGAAGCAACATCGCTCGCCATCTGCAAACCAATCTCATTCTATTTTGTGTCGGTGCTGTGGGCGCCT
	GTACTCTCTCTGTCACACAACCGTGGTACCTAGAAGTGGACTACACTCATGAGGCCGTCACCATAAA
	GTGTACCTTCTCCGCAACCGGATGCCCTTCTGAGCAACCAACATGCCTGTGGTTTCGCTACGGTGCT
	CACCAGCCTGAGAACCTGTGCTTGGACGGGTGCAAAAAAATTAAGCTGCTCAGCAAGGAACTGCGGA
	GCTTCCTGACAGCTCTTGTATCACTGCTCTCTGTCTATGTGACCGGTGTGTGCGTGGCCTTCATACT
	CCTCTCCAAATCAAAATCCAACCCTCTAAGAAAGAAAGAAATAAAAGAAGACTCACAAAAGAAGAAG
	AGTGCTCGGCGTATTTTTCAGGAAATTGCTCAAGAACTATACCATAAGAGACATGTGGAAACAAATC
	AGCAATCTGAGAAAGATAACAACACTTATGAAAACAGAAGAGTACTTTCCAACTATGAAAGGCCATA
	GAAACGTTTTAATTTTCAATGAAGTCACTGAAAATCCAACTCCAGGAGCTATGGCAGTGTTAATGAA
	CATATATCATCAGGTCTTAAAAAAAAAATAAAGGTAAACTGAAAAGACAACTGGCTACAAAGAAGGA
	TGTCAGAATGTAAGGAAACTATAACTAATAGTCATTACCAAAATACTAAAACCCAACAAAATGCAAC
	TGAAAAATACCTTCCAAATTTGCCAAGAAAAAAAATTCTATTNNAAACT
	ORF Start: ATG at 53		ORF Stop: TAG at 602
	SEQ ID NO: 140	183 aa	MW at 20846.8kD
NOV26a,	MGTASRSNIARHLQTNLILFCVGAVGACTLSVTQPWYLEVDYTHEAVTIKCTFSATGCPSEQPTCLW
CG164511-01
Protein Sequence	FRYGAHQPENLCLDGCKKIKLLSKELRSFLTALVSLLSVYVTGVCVAFILLSKSKSNPLRKKEIKED
	SQKKKSARRIFQEIAQELYHKRHVETNQQSEKDNNTYENRRVLSNYERP

[0509] Further analysis of the NOV26a protein yielded the following properties shown in Table 26B.

TABLE 26B
Protein Sequence Properties NOV26a
SignalP analysis:	Cleavage site between residues 28 and 29
PSORT II analysis:	PSG: a new signal peptide prediction method
	N-region: length 11; pos.chg 2; neg.chg 0
	H-region: length 27; peak value 10.26
	PSG score: 5.86
	GvH: von Heijne's method for signal seq. recognition
	GvH score (threshold: −2.1): −2.66
	possible cleavage site: between 30 and 31
	>>> Seems to have no N-terminal signal peptide
	ALOM: Klein et al's method for TM region allocation
	Init position for calculation: 1
	Tentative number of TMS(s) for the threshold 0.5: 2
	INTEGRAL Likelihood = −5.31 Transmembrane 17-33
	INTEGRAL Likelihood = −6.95 Transmembrane 100-116
	PERIPHERAL Likelihood = 12.04 (at 42)
	ALOM score: −6.95 (number of TMSs: 2)
	MTOP: Prediction of membrane topology (Hartmann et al.)
	Center position for calculation: 24
	Charge difference: −5.0 C(−1.5) − N(3.5)
	N >= C: N-terminal side will be inside
	>>> membrane topology: type 3a
	MITDISC: discrimination of mitochondrial targeting seq
	R content:	2	Hyd Moment(75):	3.52
	Hyd Moment(95):	4.97	G content:	3
	D/E content:	1	S/T content:	7
	Score:	−2.98
	Gavel: prediction of cleavage sites for mitochondrial preseq
	R-2 motif at 21 ARH|LQ
	NUCDISC: discrimination of nuclear localization signals
	pat4: none
	pat7: PLRKKEI (5) at 125
	bipartite: RKKEIKEDSQKKKSARR at 127
	content of basic residues: 14.2%
	NLS Score: 0.45
	KDEL: ER retention motif in the C-terminus: none
	ER Membrane Retention Signals: none
	SKL: peroxisomal targeting signal in the C-terminus: none
	PTS2: 2nd peroxisomal targeting signal: none
	VAC: possible vacuolar targeting motif: none
	RNA-binding motif: none
	Actinin-type actin-binding motif:
	type 1: none
	type 2: none
	NMYR: N-myristoylation pattern : none
	Prenylation motif: none
	memYQRL: transport motif from cell surface to Golgi: none
	Tyrosines in the tail: none
	Dileucine motif in the tail: none
	checking 63 PROSITE DNA binding motifs: none
	checking 71 PROSITE ribosomal protein motifs: none
	checking 33 PROSITE prokaryotic DNA binding motifs: none
	NNCN: Reinhardt's method for Cytoplasmic/Nuclear discrimination
	Prediction: nuclear
	Reliability: 89
	COIL: Lupas's algorithm to detect coiled-coil regions
	total: 0 residues
Final Results (k = 9/23):
39.1%: mitochondrial
34.8%: nuclear
17.4%: endoplasmic reticulum
4.3%: cytoplasmic
4.3%: peroxisomal
>> prediction for CG164511-01 is mit (k = 23)

[0510] A search of the NOV26a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 26C.

TABLE 26C
Geneseq Results for NOV26a
		NOV26a	Identities/
		Residues/	Similarities for
Geneseq	Protein/Organism/Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAW60833	Human Ig-like A07C03	1 . . . 183	167/241 (69%)	4e−86
	protein - Homo sapiens, 241	1 . . . 241	172/241 (71%)
	aa. [WO9823747-A2,
	04-JUN-1998]
AAW60834	Human Ig-like A07C03	1 . . . 183	167/241 (69%)	4e−86
	protein - Homo sapiens, 241	1 . . . 241	172/241 (71%)
	aa. [WO9823747-A2,
	04-JUN-1998]
AAY69993	Human receptor-associated	1 . . . 183	166/241 (68%)	1e−85
	protein from Incyte clone	1 . . . 241	171/241 (70%)
	1220371 - Homo sapiens,
	241 aa. [WO200008155-A2,
	17-FEB-2000]
AAY36007	Extended human secreted	1 . . . 183	166/241 (68%)	1e−85
	protein sequence,	1 . . . 241	171/241 (70%)
	SEQ ID NO. 392 - Homo sapiens,
	241 aa. [WO9931236-A2,
	24-JUN-1999]
AAY13062	Human secreted protein	1 . . . 84	84/84 (100%)	5e−47
	encoded by 5′ EST SEQ ID	1 . . . 84	84/84 (100%)
	NO: 76 - Homo sapiens, 125
	aa. [WO9906552-A2,
	11-FEB-1999]

[0511] 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	Protein/Organism/	Match	the Matched	Expect
Number	Length	Residues	Portion	Value
O95976	DORA protein	1 . . . 183	167/241 (69%)	1e−85
	precursor - Homo	1 . . . 241	172/241 (71%)
	sapiens (Human),
	241 aa.
CAC20440	Immunoglobulin	1 . . . 183	166/241 (68%)	5e−85
	superfamily 6	1 . . . 241	171/241 (70%)
	protein (IGSF6)
	precursor - Homo
	sapiens (Human),
	241 aa.
Q8WWD8	Hypothetical	1 . . . 183	164/241 (68%)	3e−84
	protein - Homo	1 . . . 241	171/241 (70%)
	sapiens (Human),
	241 aa.
Q9Z0K5	DORA protein	1 . . . 183	103/240 (42%)	7e−38
	precursor - Rattus	1 . . . 238	128/240 (52%)
	norvegicus (Rat),
	238 aa.
CAC20696	Immunoglobulin	1 . . . 179	93/236 (39%)	6e−29
	superfamily 6	1 . . . 233	116/236 (48%)
	protein (IGSF6)
	precursor - Mus
	musculus (Mouse),
	237 aa.

[0512] PFam analysis predicts that the NOV26a protein contains the domains shown in the Table 26E.

TABLE 26E
Domain Analysis of NOV26a
		Identities/
		Similarities
	NOV26a Match	for the Matched
Pfam Domain	Region	Region	Expect Value

Example 27

[0513] 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: 141	422 bp
NOV27a,	CACGCGGCCGCACCATGAAGTCCAGCGGCCTCTTCCCCTTCCTGGTGCTGCTTGCCCTGGGAACTCT
CG55060-03
DNA Sequence	GGCACCTTGGGCTGTGGAAGGCTCTGGAAAGTCCTTCAAAGCTGGAGTCTGTCCTCCTAAGAAATCT
	GCCCAGTGCCTTAGATACAAGAAACCTGAGTGCCAGAGTGACTGGCAGTGTCCAGGGAAGAAGAGAT
	GTTGTCCTGACACTTGTGGCATCAAATGCCTGGATCCTGTTGACACCCCAAACCCAACAAGGAGGAA
	GCCTGGGAAGTGCCCAGTGACTTATGGCCAATGTTTGATGCTTAACCCCCCCAATTTCTGTGAGATG
	GATGGCCAGTGCAAGCGTGACTTGAAGTGTTGCATGGGCATGTGTGGGAAATCCTGCGTTTCCCCTG
	TGAAAGCTTAGGTCGACGGC
	ORF Start: ATG at 15		ORF Stop: TAG at 411
	SEQ ID NO: 142	132 aa	MW at 14325.9kD
NOV27a,	MKSSGLFPFLVLLALGTLAPWAVEGSGKSFKAGVCPPKKSAQCLRYKKPECQSDWQCPGKKRCCPDT
CG55060-03
Protein Sequence	CGIKCLDPVDTPNPTRRKPGKCPVTYGQCLMLNPPNFCEMDGQCKRDLKCCMGMCGKSCVSPVKA
	SEQ ID NO: 143	594 bp
NOV27b,	GTCACTCCTGCCTTCACCATGAAGTCCAGCGGCCTCTTCCCCTTCCTGGTGCTGCTTGCCCTGGGAA
CG55060-01
DNA Sequence	CTCTGGCACCTTGGGCTGTGGAAGGCTCTGGAAAGTCCTTCAAAGCTGGAGTCTGTCCTCCTAAGAA
	ATCTGCCCAGTGCCTTAGATACAAGAAACCTGAGTGCCAGAGTGACTGGCAGTGTCCAGGGAAGAAG
	AGATGTTGTCCTGACACTTGTGGCATCAAATGCCTGGATCCTGTTGACACCCCAAACCCAACAAGGA
	GGAAGCCTGGGAAGTGCCCAGTGACTTATGGCCAATGTTTGATGCTTAACCCCCCCAATTTCTGTGA
	GATGGATGGCCAGTGCAAGCGTGACTTGAAGTGTTGCATGGGCATGTGTGGGAAATCCTGCGTTTCC
	CCTGTGAAAGCTTGATTCCTGCCATATGGAGGAGGCTCTGGAGTCCTGCTCTGTGTGGTCCAGGTCC
	TTTCCACCCTGAGACTTGGCTCCACCACTGATATCCTCCTTTGGGGAAAGGCTTGGCACACAGCAGG
	CTTTCAAGAAGTGCCAGTTGATCAATGAATAAATAAACGAGCCTATTTCTCTTTGCAC
	ORF Start: ATG at 19		ORF Stop: TGA at 415
	SEQ ID NO: 144	132 aa	MW at 14325.9 kD
NOV27b,	MKSSGLFPFLVLLALGTLAPWAVEGSGKSFKAGVCPPKKSAQCLRYKKPECQSDWQCPGKKRCCPDT
CG55060-01
Protein Sequence	CGIKCLDPVDTPNPTRRKPGKCPVTYGQCLMLNPPNFCEMDGQCKRDLKCCMGMCGKSCVSPVKA
	SEQ ID NO: 145	321 bp
NOV27c,	TCTGGAAAGTCCTTCAAAGCTGGAGTCTGTCCTCCTAAGAAATCTGCCCAGTGCCTTAGATACAAGA
CG55060-02
DNA Sequence	AACCTGAGTGCCAGAGTGACTGGCAGTGTCCAGGGAAGAAGAGATGTTGTCCTGACACTTGTGGCAT
	CAAATGCCTGGATCCTGTTGACACCCCAAACCCAACAAGGAGGAAGCCTGGGAAGTGCCCAGTGACT
	TATGGCCAATGTTTGATGCTTAACCCCCCCAATTTCTGTGAGATGGATGGCCAGTGCAAGCGTGACT
	TGAAGTGTTGCATGGGCATGTGTGGGAAATCCTGCGTTTCCCCTGTGAAAGCT
	ORF Start: at 1		ORF Stop: end of sequence
	SEQ ID NO: 146	107 aa	MW at 11725.8 kD
NOV27c,	SGKSFKAGVCPPKKSAQCLRYKKPECQSDWQCPGKKRCCPDTCGIKCLDPVDTPNPTRRKPGKCPVT
CG55060-02
Protein Sequence	YGQCLMLNPPNFCEMDGQCKRDLKCCMGMCGKSCVSPVKA

[0514] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 27B.

TABLE 27B
Comparison of NOV27a against NOV27b and NOV27c.
	NOV27a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV27b	1 . . . 132	132/132 (100%)
	1 . . . 132	132/132 (100%)
NOV27c	26 . . . 132	107/107 (100%)
	1 . . . 107	107/107 (100%)

[0515] Further analysis of the NOV27a protein yielded the following properties shown in Table 27C.

TABLE 27C
Protein Sequence Properties NOV27a
SignalP
analysis: Cleavage site between residues 26 and 27
PSORT II  PSG: a new signal peptide prediction method
analysis: N-region: length 2; pos.chg 1; neg.chg 0
          H-region: length 21; peak value 10.99
          PSG score: 6.59
          GvH: von Heijne's method for signal seq. recognition
          GvH score (threshold: −2.1): −1.73
          possible cleavage site: between 18 and 19
          >>> Seems to have a cleavable signal peptide (1 to 18)
          ALOM: Klein et al's method for TM region allocation
          Init position for calculation: 19
          Tentative number of TMS(s) for the threshold 0.5: 0
          number of TMS(s) . . . fixed
          PERIPHERAL Likelihood = 8.59 (at 114)
          ALOM score: 8.59 (number of TMSs: 0)
          MTOP: Prediction of membrane topology (Hartmann et al.)
          Center position for calculation: 9
          Charge difference: 0.0 C(2.0) - N(2.0)
          N >= C: N-terminal side will be inside
          MITDISC: discrimination of mitochondrial targeting seq
          R content: 0          Hyd Moment (75): 3.26
          Hyd Moment (95): 4.32 G content: 2
          D/E content: 1        S/T content: 3
          Score: −5.65
          Gavel: prediction of cleavage sites for mitochondrial preseq
          R-2 motif at 55 LRY|KK
          NUCDISC: discrimination of nuclear localization signals
          pat4: RRKP (4) at 83
          pat7: PGKKRCC (5) at 58
          pat7: PNPTRRK (3) at 79
          pat7: PTRRKPG (5) at 81
          bipartite: KKPECQSDWQCPGKKRC at 47
          content of basic residues: 15.9%
          NLS Score: 1.39
          KDEL: ER retention motif in the C-terminus: none
          ER Membrane Retention Signals:
          KKXX-like motif in the C-terminus: SPVK
          SKL: peroxisomal targeting signal in the C-terminus: none
          PTS2: 2nd peroxisomal targeting signal: none
          VAC: possible vacuolar targeting motif: none
          RNA-binding motif: none
          Actinin-type actin-binding motif:
          type 1: none
          type 2: none
          NMYR: N-myristoylation pattern: none
          Prenylation motif: none
          memYQRL: transport motif from cell surface to Golgi: none
          Tyrosines in the tail: none
          Dileucine motif in the tail: none
          checking 63 PROSITE DNA binding motifs: none
          checking 71 PROSITE ribosomal protein motifs: none
          checking 33 PROSITE prokaryotic DNA binding motifs: none
          NNCN: Reinhardt's method for Cytoplasmic/Nuclear
          discrimination
          Prediction: nuclear
          Reliability: 94.1
          COIL: Lupas's algorithm to detect coiled-coil regions
          total: 0 residues
          ----------------------------------
          Final Results (k = 9/23):
          60.9%: nuclear
          17.4%: mitochondrial
          17.4%: extracellular, including cell wall
          4.3%: cytoplasmic
          >> prediction for CG55060-03 is nuc (k = 23)

[0516] 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 27D.

TABLE 27D
Geneseq Results for NOV27a
		NOV27a	Identities/
	Protein/Organism/	Residues/	Similarities for
Geneseq	Length	Match	the Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
AAU11763	Human	1 . . . 132	132/132	2e−81
	Antileukoprotease	1 . . . 132	(100%)
	protein - Homo		132/132
	sapiens, 132 aa.		(100%)
	[WO200190421-A2,
	29-NOV-2001]
AAB66864	Human	1 . . . 132	132/132	2e−81
	antileukoprotease -	1 . . . 132	(100%)
	Homo sapiens,		132/132
	132 aa.		(100%)
	[WO200101998-A2,
	11-JAN-2001]
AAB47403	SLPI native	1 . . . 132	132/132	2e−81
	immature form -	1 . . . 132	(100%)
	Homo sapiens,		132/132
	132 aa.		(100%)
	[WO200148231-A2,
	05-JUL-2001]
ABB50282	Leukocyte protease	1 . . . 132	132/132	2e−81
	inhibitor ovarian	1 . . . 132	(100%)
	tumour marker		132/132
	protein, #54 - Homo		(100%)
	sapiens, 132 aa.
	[WO200175177-A2,
	11-OCT-2001]
AAR84056	Secretory leukocyte	1 . . . 132	132/132	2e−81
	protease inhibitor -	1 . . . 132	(100%)
	Homo sapiens,		132/132
	132 aa.		(100%)
	[WO9608275-A1,
	21-MAR-1996]

[0517] 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 27E.

TABLE 27E
Public BLASTP Results for NOV27a
			Identities/
		NOV27a	Similarities
Protein		Residues/	for the
Accession	Protein/Organism/	Match	Matched	Expect
Number	Length	Residues	Portion	Value
P03973	Antileukoproteinase	1 . . . 132	132/132	5e−81
	1 precursor (ALP)	1 . . . 132	(100%)
	(HUSI-1) (Seminal		132/132
	proteinase inhibitor)		(100%)
	(Secretory leukocyte
	protease inhibitor)
	(BLPI) (Mucus
	proteinase inhibitor)
	(MPI) - Homo
	sapiens (Human),
	132 aa.
CAA00747	ALP-242	26 . . . 132	106/107	9e−66
	PROTEIN -	1 . . . 107	(99%)
	synthetic construct,		107/107
	107 aa (fragment).		(99%)
CAA00748	ALP-246	26 . . . 132	105/107	1e−64
	PROTEIN -	1 . . . 107	(98%)
	synthetic construct,		106/107
	107 aa (fragment).		(98%)
CAA00743	ALP-231	26 . . . 132	103/107	1e−64
	PROTEIN -	1 . . . 107	(96%)
	synthetic construct,		107/107
	107 aa (fragment).		(99%)
CAA00742	ALP-240	26 . . . 132	105/107	1e−64
	PROTEIN -	1 . . . 107	(98%)
	synthetic construct,		106/107
	107 aa (fragment).		(98%)

[0518] PFam analysis predicts that the NOV27a protein contains the domains shown in the Table 27F.

TABLE 27F
Domain Analysis of NOV27a
		Identities/
	NOV27a Match	Similarities for the
Pfam Domain	Region	Matched Region	Expect Value
wap	31 . . . 75	23/55 (42%)	1.8e−18
		45/55 (82%)
wap	85 . . . 129	25/55 (45%)	7e−21
		43/55 (78%)

Example 28

[0519] 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: 147	1542 bp
NOV28a,	AAACGATTTCATGATGTGCTGGGCAATGAAAGACCTTCTGCTTACATGAGGGAGCACAATCAATTAA
CG56972-02
DNA Sequence	ATGGCTGGTCTTCTGATGAAAATGACTGGAATGAAAAACTCTACCCAGTGTGGAACCGGGGAGACAT
	GAGGTGGAAAAACTCCTGGAAGCGAGGCCGTGTGCAGGCCGTCCTGACCAGTQACTCACCAGCCCTC
	GTGGGCTCAAATATAACATTTGCGGTGAACCTGATATTCCCTAGATGCCAAAAGGAAGATGCCAATG
	GCAACATAGTCTATGAGAAGAACTGCAGAAATGAGGCTGGTTTATCTGCTGATCCATATGTTTACAA
	CTGGACAGCATCGTCAGAGGACAGTGACGGGGAAAATGGCACCGGCCAAAGCCATCATAACGTCTTC
	CCTGATGGGAAACCTTTTCCTCACCACCCCGGATGGAGAAGATGGAATTTCATCTACGTCTTCCACA
	CACTTGGTCAGTATTTCCAGAAATTGGGACGATGTTCAGTGAGAGTTTCTGTGAACACAGCCAATGT
	GACACTTGGGCCTCAACTCATGGAAGTGACTQTCTACAGAAGACATGGACGGGCATATGTTCCCATC
	GCACAAATGAAAGATGTGTACGTGGTAACAGATCAGATTCCTGTGTTTGTGACTATGTTCCAGAAGA
	ACGATCGAAATTCATCCGACGAAACCTTCCTCAAAGATCTCCCCATTATGTTTGATCTCCTGATTCA
	TGATCCTAGCACTTCCTCAATTATTCTACCATTAACTACAAGTCGAGCTTCGGCGATAATACTCGC
	CTGTTTGTTTCCACCAATCATACTGTGAATCACACGTATGTGCTCAATGGAACCTTCAGCCTTAACC
	TCACTGTGAAAGCTGCAGCACCAGCACCTTGTCCGCCACCGCCACCACCACCCAGACCTTCAAAACC
	CACCCCTTCTTTAGGACCTGCTCGTGACAACCCCCTGGAGCTGAGTAGCATTCCTCATGAAAACTGC
	CAGATTAACAGATATGGCCACTTTCAAGCCACCATCACAATTGTAGAGGGAATCTTAGAGGTTAACA
	TCATCCAGATGACAGACCTCCTGATGCCGGTGCCATCGCCTGAAAGCTCCCTAATAGACTTTGTCGT
	GACCTGCCAAGGGAGCATTCCCACGGAGGTCTGTACCATCATTTCTGACCCCACCTCCGAGATCACC
	CAGAACACAGTCTGCAGCCCTGTGGATGTGGATGAGATGTGTCTGCTGACTGTGAGACGAACCTTCA
	ATGGGTCTGGGACGTACTGTGTAAACCTCACCCTGGGCGATGACACAPCCCTCGCTCTCACGAGCAC
	CCTGATTTCTGTTCCTGACAGAGACCCAGCCTCGCCTTTAAGGATCGCAAACAGTGCCCTGATCTCC
	GTTGGCTGCTTGGCCATATTTGTCACTGTGATCTCCCTCTTGGTGTACAAAAAACACAAGGAATACA
	ACCCAATAGAAAATAGTCCTGGGAATGTGGTCACAAGCAAACGCCTGAGTGTCTTTCTCAACCGTGC
	A
ORF Start: at 1	ORF Stop: end of sequence
SEQ ID NO: 148	514 aa	MW at 57453.5 kD
NOV28a,	KRFHDVLGNERPSAYMREHNQLNGWSSDENDWNEKLYPVWKRGDMRWKNSWKGGRVQAVLTSDSPAL
CG56972-02
Protein Sequence	VGSNITFAVNLTFPRCQKEDANGNIVYEKNCRNEAGLSADPYVYNWTAWSEDSDGENGTGQSHHNVF
	PDGKPFPHHPGWRRWNFIYVFHTLGQYFQKLGRCSVRVSVNTANVTLGPQLMEVTVYRRHGRAYVPI
	AQVKDVYVVTDQIPVFVTMFQKNDRNSSDETFLKDLPIMFDVLIHDPSHFLNYSTINYKWSFGDNTG
	LFVSTNHTVNHTYVLNGTFSLNLTVKAAAPGPCPPPPPPPRPSKPTPSLGPAGDNPLELSRIPDENC
	QINRYGHFQATITIVEGILEVNIIQMTDVLMPVPWPESSLIDFVVTCQGSIPTEVCTIISDPTCEIT
	QNTVCSPVDVDEMCLLTVRRTFNGSGTYCVNLTLGDDTSLALTSTLISVPDRDPASPLRMANSALIS
	VGCLAIFVTVISLLVYKKHKEYNPIENSPGNVVRSKGLSVFLNRA
	SEQ ID NO: 149	1410 bp
NOV28b,	AAACGATTTCATGATGTGCTGGGCAATGAAAGACCTTCTGCTTACATGAGGGAGCACAATCAATTAA
CG56972-03
DNA Sequence	ATGGCTGGTCTTCTGATGAAAATGACTGGAATGAAAAACTCTACCCAGTGTCGAAGCGGCGAGACAT
	GAGGTGGAAAAACTCCTGGAAGGGACGCCGTGTGCAGGCGGTCCTGACCAGTGACTCACCAGCCCTC
	GTGGGCTCAAATATAACATTTGCGGTGAACCTGATATTCCCTAGATCCCAAAAGGAAGATGCCAATG
	GCAACATAGTCTATGAGAAGAACTGCAGAAATGAGGCTGGTTTATCTGCTGATCCGTATGTTTACAA
	CTGGACAGCATGGTCAGAGGACAGTGACGGGGAAAATGGCACCGGCCAAAGCCATCATAACGTCTTC
	CCTGATGGGAAACCTTTTCCTCACCACCCCGGATCGAGAAGATGGAATTTCATCTACGTCTTCCACA
	CACTTGCTCAGTATTTCCAGAAATTGGGACGATGTTCAGTGAGAGTTTCTGTGAACACAGCCAATGT
	GACACTTGGGCCTCAACTCATGGAAGTGACTGTCTACAGAAGACATGGACCGGCATATGTTCCCATC
	GCACAAGTGAAAGATGTGTACGTGGTAACAGATCAGATTCCTGTGTTTGTGACTATGTTCCAGAAGA
	ACGATCGAAATTCATCCGACGAAACCTTCCTCAAAGATCTCCCCATTATGTTTGATGTCCTGATTCA
	TGATCCTAGCCACTTCCTCAATTATTCTACCATTAACTACAAGTCGAGCTTCGGGGATAATACTGGC
	CTGTTTGTTTCCACCAATCATACTGTGAATCACACGTATGTGCTCAATGGAACCTTCAGCCTTAACC
	TCACTGTGAAAGCTGCAGCACCAGGACCTTGTCCGCCACCGCCACCACCACCCAGACCTTCAAAACC
	CACCCCTTCTTTAGCAACTACTCTAAAATCTTATGATTCAAACACCCCAGGACCTGCTGCTGACAAC
	CCCCTGGAGCTGAGTAGGATTCCTGATGAAAACTCCCAGATTAACAGATATGGCCACTTTCAAGCCA
	CCATCACAATTGTAGAGGGAATCTTAGAGGTTAACATCATCCACATGACAGACGTCCTGATGCCGGT
	GCCATGGCCTGAAAGCTCCCTAATAGACTTTGTCGTGACCTGCCAACGGAGCATTCCCACGGACGTC
	TGTACCATCATTTCTCACCCCACCTGCGAGATCACCCAGAACACAGTCTGCAGCCCTGTGGATGTGG
	ATGAGATGTGTCTGCTGACTGTGACACQAACCTTCAATGGGTCTGGGACGTACTGTGTGAACCTCAC
	CCTGGGGGATGACACAAGCCTGGCTCTCACGAGCACCCTGATTTCTGTTCCTGACAGAGACCCAGCC
	TCG
	ORF Start: at 1	ORF Stop: end of sequence
	SEQ ID NO: 150	470 aa	MW at 52621.7 kD
NOV28b,	KRFHDVLGNERPSAYMREHNQLNGWSSDENDWNEKLYPVWKRGDMRWKNSWKGGRVQAVLTSDSPAL
CG56972-03
Protein Sequence	VGSNITFAVNLIFPRCQKEDANGNIVYEKNCRNEAGLSADPYVYNWTAWSEDSDGENGTGQSHHNVF
	PDGKPFPHMPGWRRWNFIYVFHTLGQYFQKLGRCSVRVSVNTANVTLGPQLMEVTVYRRHCRAYVPI
	AQVKDVYVVTDQIPVFVTMFQKNDRNSSDETFLKDLPIMFDVLIHDPSHFLNYSTINYKWSFGDNTG
	LFVSTNHTVNHTYVLNGTFSLNLTVKAAAPGPCPPPPPPPRPSKPTPSLATTLKSYDSNTPGPAGDN
	PLELSRIPDENCQINRYGHFQATITIVEGILEVNIIQMTDVLMPVPWPESSLIDFVVTCQGSIPTEV
	CTIISDPTCEITQNTVCSPVDVDEMCLLTVRRTFNGSGTYCVNLTLGDDTSLAITSTLISVPDRDPA
	S
	SEQ ID NO: 151	1923 bp
NOV28c,	NGNCAGATGCCAGAAGAACACTGTTGCTCTTGGTGGACCGCCCCAGAGGAATTCAGAGTTAAACCTT
CG56972-01
DNA Sequence	GAGTGCCTCCGTCCGTGAGAATTCAGCATGGAATGTCTCTACTATTTCCTGGGATTTCTGCTCCTGG
	CTGCAAGATTGCCACTTGATGCCGCCAAACGATTTCATGATGTGCTGGGCAATGAAAGACCTTCTGC
	TTACATGAGGGAGCACAATCAATTAAATGGCTGGTCTTCTGATGAAAATGACTGGAATGAAAAACTC
	TACCCAGTCTGGAAGCCGGGAGACATGAGGTGGAAAAACTCCTGGAAGGGAGGCCGTGTGCAGGCGG
	TCCTGACCAGTGACTCACCAGCCCTCGTGGGCTCAAATATAACATTTGCGGTGAACCTGATATTCCC
	TAGATGCCAAAACGAAGATGCCAATGGCAACATAGTCTATGAGAACAACTGCAGAAATGAGGCTGGT
	TTATCTGCTGATCCATATGTTTACAACTGGACAGCATGGTCACAGGACAGTGACGGGGAAAATCGCA
	CCGGCCAAAGCCATCATAACGTCTTCCCTGATGGGAAACCTTTTCCTCACCACCCCGGATGGAGAAG
	ATGCAATTTCATCTACGTCTTCCACACACTTGGTCACTATTTCCAGAAATTGGGACGATGTTCAGTG
	ACAGTTTCTGTGAACACAGCCAATGTGACACTTGGGCCTCAACTCATGGAAGTGACTGTCTACAGAA
	GACATGGACGGGCATATGTTCCCATCGCACAAGTQAAAGATGTGTACGTGGTAACAGATCAGATTCC
	TGTGTTTGTGACTATGTTCCAGAAGAACCATCGAAATTCATCCGACGAAACCTTCCTCAAAGATCTC
	CCCATTATGTTTCATGTCCTGATTCATGATCCTAGCCACTTCCTCAATTATTCTACCATTAACTACA
	AGTGGAGCTTCGGGGATAATACTGGCCTGTTTGTTTCCACCAATCATACTGTGAATCACACGTATGT
	GCTCAATGGAACCTTCAGCCTTAACCTCACTGTGAAAGCTGCAGCACCAGGACCTTGTCCGCCACCG
	CCACCACCACCCAGACCTTCAAAACCCACCCCTTCTTTAGGACCTGCTGGTGACAACCCCCTGGAGC
	TGAGTAGGATTCCTGATGAAAACTGCCAGATTAACAGATATGGCCACTTTCAAGCCACCATCACAAT
	TGTACAGGCAATCTTAGAGGTTAACATCATCCAGATGACAGACGTCCTGATGCCGGTGCCATGGCCT
	GAAAGCTCCCTAATAGACTTTGTCGTGACCTGCCAAGGGAGCATTCCCACGGAGGTCTGTACCATCA
	TTTCTGACCCCACCTGCGAGATCACCCAGAACACAGTCTGCAGCCCTGTGGATGTQGATGAGATGTG
	TCTGCTGACTGTGAGACGAACCTTCAATGGGTCTGGGACGTACTGTGTGAACCTCACCCTGGCGGAT
	GACACAAGCCTGGCTCTCACGAGCACCCTGATTTCTGTTCCTGACAGAGACCCAGCCTCGCCTTTAA
	GGATGGCAAACAGTGCCCTGATCTCCGTTGGCTGCTTGGCCATATTTCTCACTGTGATCTCCCTCTT
	GGTGTACAAAAAACACAAGGAATACAACCCAATAGAAAATAGTCCTCGGAATGTGGTCAGAAGCAAA
	GGCCTGAGTGTCTTTCTCAACCGTGCAAAAGCCGTGTTCTTCCCGGGAAACCAGGAAAAGGATCCGC
	TACTCAAAAACCAAGAATTTAAAGGAGTTTCTTAAATTTCGACCTTGTTTCTGAAGCTCACTTTTCA
	GTGCCATTGATGTGAGATGTGCTGGAGTCGCTATTAACCTTTTTTTCCTAAAGATTATTGTTAAATA
	GATATTGTGGTTTGGGGAAGTTGAATTTTTTATAGGTTAAATGTCAT
	ORF Start: ATG at 95	ORF Stop: TAA at 1775
	SEQ ID NO: 152	560 aa	MW at 62642.6 kD
NOV28c,	MECLYYFLQFLLLAARLPLDAAKRFHDVLGNERPSAYMREHNQLNGWSSDENDWNEKLYPVWKRGDM
CG56972-01
Protein Sequence	RWKNSWKGGRVQAVLTSDSPALVGSNITFAVNLIFPRCQKEDANGNIVYEKNCRNEAGLSADPYVYN
	WTAWSEDSDGENGTGQSHHNVFPDGKPFPHHPGWRRWNFIYVFHTLGQYFQKLGRCSVRVSVNTANV
	TLGPQLMEVTVYRRHGRAYVPIAQVKDVYVVTDQIPVFVTMFQKNDRNSSDETFLKDLPIMFDVLIH
	DPSHFLNYSTINYKWSFGDNTGLFVSTNHTVNHTYVLNGTFSLNLTVKAAAPGPCPPPPPPPRPSKP
	TPSLGPAGDNPLELSRIPDENCQINRYGHFQATITIVEGILEVNIIQMTDVLMPVPWPESSLIDFVV
	TCQCSIPTEVCTIISDPTCEITQNTVCSPVDVDEMCLLTVRRTFNGSGTYCVNLTLGDDTSLALTST
	LISVPDRDPASPLRMANSALISVGCLAIFVTVISLLVYKKHKEYNPIENSPGNVVRSKGLSVFLNPA
	KAVFFPGNQEKDPLLKNQEFKGVS
	SEQ ID NO: 153	1393 bp
NOV28d,	CACCGGATCCAAACGATTTCATGATGTGCTGGGCAATGAAAGACCTTCTGCTTACATGAGGGAGCAC
255623772 DNA
Sequence	AATCAATTAAATGGCTGGTCTTCTGATGAAAATGACTGGAATGAAAAACTCTACCCAGTGTGGAAGC
	GGGGAGACATGAGGTGGAAAAACTCCTGGAAGGGAGGCCGTGTGCACGCGGTCCTGACCAGTGACTC
	ACCAGCCCTCGTGGGCTCAAATATAACATTTGCGGTGAACCTGATATTCCCTAGATGCCAAAAGGAA
	GATGCCAATGGCAACATAGTCTATGAGAAGAACTCCAGAAATCAGGCTGGTTTATCTGCTGATCCGT
	ATGTTTACAACTGGACAGCATGGTCAGAGGACAGTGACGGGGAAAATCGCACCGGCCAAAGCCATCA
	TAACGTCTTCCCTGATGGGAAACCTTTTCCTCACCACCCCGGATGGACAAGATGGAATTTCATCTAC
	GTCTTCCACACACTTGGTCAGTATTTCCAGAAATTGGGACGATGTTCAGTGAGAGTTTCTGTGAACA
	CAGCCAATGTGACACTTCGGCCTCAACTCATGGAAGTGACTGTCTACAGAAGACATGGACGGGCATA
	TGTTCCCATCGCACAAGTGAAAGATGTGTACGTGGTAACAGATCAGATTCCTGTGTTTGTGACTATG
	TTCCAGAAGAACGATCGAAATTCATCCGACGAAACCTTCCTCAAAGATCTCCCCATTATGTTTGATG
	TCCTGATTCATGATCCTAGCCACTTCCTCAATTATTCTACCATTAACTACAAGTGGAGCTTCGGGGA
	TAATACTGGCCTGTTTGTTTCCACCAATCATACTGTGAATCACACGTATGTGCTCAATGGAACCTTC
	AGCCTTAACCTCACTGTGAAAGCTGCAGCACCACGACCTTGTCCCCCACCGCCACCACCACCCAGAC
	CTTCAAAACCCACCCCTTCTTTAGGACCTGCTGGTGACAACCCCCTGGAGCTGAGTAGGATTCCTGA
	TGAAAACTGCCAGATTAACAGATATGGCCACTTTCAAGCCACCATCACAATTGTAGAGGGAATCTTA
	GAGGTTAACATCATCCAGATGACAGACGTCCTGATGCCGGTGCCATCGCCTGAAAGCTCCCTAATAG
	ACTTTGTCGTGACCTGCCAAGGGAGCATTCCCACGGAGGTCTGTACCATCATTTCTGACCCCACCTG
	CGAGATCACCCAGAACACAGTCTGCAGCCCTGTGGATGTCGATGAGATGTGTCTGCTGACTGTGAGA
	CGAACCTTCAATGGGTCTGGGACGTACTGTGTGAACCTCACCCTCGGGGATGACACAAGCCTCGCTC
	TCACGAGCACCCTGATTTCTGTTCCTGACAGAGACCCAGCCTCGCTCGAGGGC
	ORF Start: at 2	ORF Stop: end of sequence
	SEQ ID NO: 154	464 aa	MW at 51886.9 kD
NOV28d	TGSKRFHDVLGNERPSAYMREHNQLNGWSSDENDWNEKLYPVWKRGDMRWKNSWKGCRVQAVLTSDS
255623772
Protein Sequence	PALVGSNITFAVNLIFPRCQKEDANGNIVYEKNCRNEAGLSADPYVYNWTAWSEDSDGENGTCQSHH
	NVFPDGKPFPHHPGWRRWNFIYVFHTLGQYFQKLGRCSVRVSVNTANVTLGPQLMEVTVYRRHGRAY
	VPIAQVKDVYVVTDQIPVFVTMFQKNDRNSSDETFLKDLPIMPDVLIHDPSHFLNYSTINYKWSFGD
	NTGLFVSTNHTVNHTYVLNGTFSLNLTVKAAAPGPCPPPPPPPRPSKPTPSLGPAGDNPLELSRIPD
	ENCQINRYGHFQATITIVEGILEVNIIQMTDVLMPVPWPESSLIDFVVTCQGSIPTEVCTIISDPTC
	EITQNTVCSPVDVDEMCLLTVRRTFNGSGTYCVNLTLGDDTSLALTSTLISVPDRDPASLEG

[0520] Sequence comparison of the above protein sequences yields the following sequence relationships shown in Table 28B.

TABLE 28B
Comparison of NOV28a against NOV28b through NOV28d.
	NOV28a Residues/	Identities/Similarities
Protein Sequence	Match Residues	for the Matched Region
NOV28b	1 . . . 458	458/470 (97%)
	1 . . . 470	458/470 (97%)
NOV28c	1 . . . 514	514/514 (100%)
	23 . . . 536	514/514 (100%)
NOV28d	1 . . . 458	458/458 (100%)
	4 . . . 461	458/458 (100%)

[0521] Further analysis of the NOV28a protein yielded the following properties shown in Table 28C.

TABLE 28C
Protein Sequence Properties NOV28a
SignalP
analysis: No Known Signal Sequence Predicted
PSORT II  PSG: a new signal peptide prediction method
analysis: N-region: length 11; pos. chg 3; neg. chg 2
          H-region: length 5; peak value −9.84
          PSG score: −14.24
          GvH: von Heijne's method for signal seq. recognition
          GvH score (threshold: −2.1): −13.12
          possible cleavage site: between 61 and 62
          >>> Seems to have no N-terminal signal peptide
          ALOM: Klein et al's method for TM region allocation
          Init position for calculation: 1
          Tentative number of TMS(s) for the threshold 0.5: 1
          Number of TMS(s) for threshold 0.5: 1
          INTEGRAL Likelihood = −10.19
          Transmembrane 468-484
          PERIPHERAL Likelihood = 1.80 (at 343)
          ALOM score: −10.19 (number of TMSs: 1)
          MTOP: Prediction of membrane topology (Hartmann et al.)
          Center position for calculation: 475
          Charge difference: 1.5 C (1.5) - N (0.0)
          C > N: C-terminal side will be inside
          >>> Single TMS is located near the C-terminus
          >>> membrane topology: type Nt (cytoplasmic tail 1 to 467)
          MITDISC: discrimination of mitochondrial targeting seq
          R content: 1           Hyd Moment (75): 8.66
          Hyd Moment (95): 14.16 G content: 1
          D/E content: 2         S/T content: 0
          Score: −5.32
          Gavel: prediction of cleavage sites for mitochondrial preseq
          R-2 motif at 12 KRF|HD
          NUCDISC: discrimination of nuclear localization signals
          pat4: KKHK (3) at 486
          pat7: none
          bipartite: none
          content of basic residues: 8.6%
          NLS Score: −0.29
          KDEL: ER retention motif in the C-terminus: none
          ER Membrane Retention Signals:
          XXRR-like motif in the N-terminus: RFHD
          none
          SKL: peroxisomal targeting signal in the C-terminus: NRA
          PTS2: 2nd peroxisomal targeting signal: none
          VAC: possible vacuolar targeting motif: none
          RNA-binding motif: none
          Actinin-type actin-binding motif:
          type 1: none
          type 2: none
          NMYR: N-myristoylation pattern: none
          Prenylation motif: none
          memYQRL: transport motif from cell surface to Golgi: none
          Tyrosines in the tail: too long tail
          Dileucine motif in the tail: found
          LL at 417
          checking 63 PROSITE DNA binding motifs: none
          checking 71 PROSITE ribosomal protein motifs: none
          checking 33 PROSITE prokaryotic DNA binding motifs: none
          NNCN: Reinhardt's method for Cytoplasmic/Nuclear
          discrimination
          Prediction: cytoplasmic
          Reliability: 76.7
          COIL: Lupas's algorithm to detect coiled-coil regions
          total: 0 residues
          ----------------------------------
          Final Results (k = 9/23):
          26.1%: cytoplasmic
          26.1%: nuclear
          13.0%: Golgi
          8.7%: mitochondrial
          8.7%: vesicles of secretory system
          8.7%: peroxisomal
          8.7%: endoplasmic reticulum
          >> prediction for CG56972-02 is cyt (k = 23)

[0522] 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
			Identities/
		NOV28a	Similarities
	Protein/Organism/	Residues/	for the
Geneseq	Length	Match	Matched	Expect
Identifier	[Patent #, Date]	Residues	Region	Value
ABP61881	Human lung cancer	1 . . . 514	514/514	0.0
	associated protein	23 . . . 536	(100%)
	sequence SEQ ID		514/514
	NO:225 - Homo		(100%)
	sapiens, 560 aa.
	[WO200247534-A2,
	20-JUN-2002]
ABB74961	Human lung tumour	1 . . . 514	514/514	0.0
	L528S protein	23 . . . 536	(100%)
	sequence SEQ ID		514/514
	NO:225 - Homo		(100%)
	sapiens, 560 aa.
	[WO200200174-A2,
	03-JAN-2002]
AAB11329	Human lung cancer-	1 . . . 514	514/514	0.0
	associated protein	23 . . . 536	(100%)
	L528S - Homo		514/514
	sapiens, 560 aa.		(100%)
	[WO200061612-A2,
	19-OCT-2000]
AAW35382	Murine metastatic	1 . . . 514	514/514	0.0
	nucleic acid	23 . . . 536	(100%)
	sequence product -		514/514
	Mus musculus,		(100%)
	560 aa.
	[WO9718454-A2,
	22-MAY-1997]
AAU83612	Human PRO	1 . . . 514	513/526	0.0
	protein, Seq ID No	23 . . . 548	(97%)
	42 - Homo sapiens,		513/526
	572 aa.		(97%)
	[WO200208288-A2,
	31-JAN-2002]

[0523] 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
Protein		Residues/	Identities/
Accession		Match	Similarities for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
Q14956	Putative transmembrane	1 . . . 514	514/514 (100%)	0.0
	protein NMB precursor	23 . . . 536	514/514 (100%)
	(Transmembrane
	glycoprotein HGFIN) - Homo
	sapiens (Human), 560 aa.
Q8N1A1	Similar to glycoprotein	1 . . . 514	514/526 (97%)	0.0
	(Transmembrane) nmb -	23 . . . 548	514/526 (97%)
	Homo sapiens (Human), 572
	aa.
Q9QXA0	Putative transmembrane	1 . . . 514	375/530 (70%)	0.0
	glycoprotein - Mus musculus	23 . . . 552	440/530 (82%)
	(Mouse) 574 aa.
Q99P91	Dendritic cell-associated	1 . . . 514	375/530 (70%)	0.0
	transmembrane protein	23 . . . 552	440/530 (82%)
	(Glycoprotein
	(Transmembrane) nmb) -
	Mus musculus (Mouse), 574
	aa.
Q9QZF6	Osteoactivin - Rattus	1 . . . 514	369/528 (69%)	0.0
	norvegicus (Rat), 572 aa.	23 . . . 550	439/528 (82%)

[0524] PFam analysis predicts that the NOV28a protein contains the domains shown in the Table 28F.

TABLE 28F
Domain Analysis of NOV28a
		Identities/
		Similarities
		for the Matched	Expect
Pfam Domain	NOV28a Match Region	Region	Value

Example B

[0525] Sequencing Methodology and Identification of NOVX Clones

[0526] 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.

[0527] 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.

[0528] 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.

[0529] The laboratory screening was performed using the methods summarized below:

[0530] 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).

[0531] 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.

[0532] 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).

[0533] 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.

[0534] 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.

[0535] 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.

[0536] 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

[0537] Quantitative Expression Analysis of Clones in Various Cells and Tissues

[0538] The quantitative expression of various clones was assessed using microtiter plates containing RNA samples from a variety of normal and pathology-derived cells, cell lines and tissues using real time quantitative PCR (RTQ PCR). RTQ PCR was performed on an Applied Biosystems ABI PRISM® 7700 or an ABI PRISM® 7900 HT Sequence Detection System. Various collections of samples are assembled on the plates, and referred to as Panel 1 (containing normal tissues and cancer cell lines), Panel 2 (containing samples derived from tissues from normal and cancer sources), Panel 3 (containing cancer cell lines), Panel 4 (containing cells and cell lines from normal tissues and cells related to inflammatory conditions), Panel 5D/5I (containing human tissues and cell lines with an emphasis on metabolic diseases), AI_comprehensive_panel (containing normal tissue and samples from autoinflammatory diseases), Panel CNSD.01 (containing samples from normal and diseased brains) and CNS_neurodegeneration_panel (containing samples from normal and Alzheimer's diseased brains).

[0539] 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.

[0540] 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.

[0541] 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.

[0542] 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.

[0543] 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.

[0544] 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.

[0545] Panels 1, 1.1, 1.2, and 1.3D

[0546] 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.

[0547] In the results for Panels 1, 1.1, 1.2 and 1.3D, the following abbreviations are used:

[0548] ca.=carcinoma,

[0549] *=established from metastasis,

[0550] met=metastasis,

[0551] s cell var=small cell variant,

[0552] non-s=non-sm=non-small,

[0553] squam=squamous,

[0554] pl. eff=pl effusion=pleural effusion,

[0555] glio=glioma,

[0556] astro=astrocytoma, and

[0557] neuro=neuroblastoma.

[0558] General_screening_panel_v1.4, v1.5, v1.6 and 1.7

[0559] The plates for Panels 1.4, 1.5, 1.6 and 1.7 include 2 control wells (genomic DNA control and chemistry control) and 88 to 94 wells containing cDNA from various samples. The samples in Panels 1.4, 1.5, 1.6 and 1.7 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, 1.6 and 1.7 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, 1.6 and 1.7 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.

[0560] Panels 2D, 2.2, 2.3 and 2.4

[0561] The plates for Panels 2D, 2.2, 2.3 and 2.4 generally include 2 control wells and 94 test samples composed of RNA or cDNA isolated from human tissue procured by surgeons working in close cooperation with the National Cancer Institute's Cooperative Human Tissue Network (CHTN) or the National Disease Research Initiative (NDRI) or from Ardais or Clinomics). The tissues are derived from human malignancies and in cases where indicated many malignant tissues have “matched margins” obtained from noncancerous tissue just adjacent to the tumor. These are termed normal adjacent tissues and are denoted “NAT” in the results below. The tumor tissue and the “matched margins” are evaluated by two independent pathologists (the surgical pathologists and again by a pathologist at NDRI/CHTN/Ardais/Clinomics). Unmatched RNA samples from tissues without malignancy (normal tissues) were also obtained from Ardais or Clinomics. This analysis provides a gross histopathological assessment of tumor differentiation grade. Moreover, most samples include the original surgical pathology report that provides information regarding the clinical stage of the patient. These matched margins are taken from the tissue surrounding (i.e. immediately proximal) to the zone of surgery (designated “NAT”, for normal adjacent tissue, in Table RR). In addition, RNA and cDNA samples were obtained from various human tissues derived from autopsies performed on elderly people or sudden death victims (accidents, etc.). These tissues were ascertained to be free of disease and were purchased from various commercial sources such as Clontech (Palo Alto, Calif.), Research Genetics, and Invitrogen.

[0562] HASS Panel v 1.0

[0563] 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.

[0564] ARDAIS Panel v 1.0

[0565] 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.

[0566] Panel 3D, 3.1 and 3.2

[0567] 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.

[0568] Panels 4D, 4R, and 4.1D

[0569] 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.).

[0570] 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.

[0571] Mononuclear cells were prepared from blood of employees at CuraGen Corporation, using Ficoll. LAK cells were prepared from these cells by culture in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco/Life Technologies, Rockville, Md.), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), and 10 mM Hepes (Gibco) and Interleukin 2 for 4-6 days. Cells were then either activated with 10-20 ng/ml PMA and 1-2 μg/ml ionomycin, IL-12 at 5-10 ng/ml, IFN gamma at 20-50 ng/ml and IL-18 at 5-10 ng/ml for 6 hours. In some cases, mononuclear cells were cultured for 4-5 days in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), and 10 mM Hepes (Gibco) with PHA (phytohemagglutinin) or PWM (pokeweed mitogen) at approximately 5 μg/ml. Samples were taken at 24, 48 and 72 hours for RNA preparation. MLR (mixed lymphocyte reaction) samples were obtained by taking blood from two donors, isolating the mononuclear cells using Ficoll and mixing the isolated mononuclear cells 1:1 at a final concentration of approximately 2×106 cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol (5.5×10−5M) (Gibco), and 10 mM Hepes (Gibco). The MLR was cultured and samples taken at various time points ranging from 1-7 days for RNA preparation.

[0572] Monocytes were isolated from mononuclear cells using CD14 Miltenyi Beads, +ve VS selection columns and a Vario Magnet according to the manufacturer's instructions. Monocytes were differentiated into dendritic cells by culture in DMEM 5% fetal calf serum (FCS) (Hyclone, Logan, Utah), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), and 10 mM Hepes (Gibco), 50 ng/ml 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.

[0573] 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.

[0574] 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 resuspended at 106 cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), and 10 mM Hepes (Gibco). To activate the cells, we used PWM at 5 μg/ml or anti-CD40 (Pharmingen) at approximately 10 μg/ml and IL-4 at 5-10 ng/ml. Cells were harvested for RNA preparation at 24,48 and 72 hours.

[0575] 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 2μg/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 μg/ml) to prevent apoptosis. After 4-5 days, the Th1, Th2 and Tr1 lymphocytes were washed and then expanded again with IL-2 for 4-7 days. Activated Th1 and Th2 lymphocytes were maintained in this way for a maximum of three cycles. RNA was prepared from primary and secondary Th1, Th2 and Tr1 after 6 and 24 hours following the second and third activations with plate bound anti-CD3 and anti-CD28 mAbs and 4 days into the second and third expansion cultures in Interleukin 2.

[0576] 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 5×105cells/ml. For the culture of these cells, we used DMEM or RPMI (as recommended by the ATCC), with the addition of 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), 10 mM Hepes (Gibco). RNA was either prepared from resting cells or cells activated with PMA at 10 ng/ml and ionomycin at 1 μg/ml for 6 and 14 hours. Keratinocyte line CCD106 and an airway epithelial tumor line NCI-H292 were also obtained from the ATCC. Both were cultured in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), and 10 mM Hepes (Gibco). CCD1106 cells were activated for 6 and 14 hours with approximately 5 ng/ml TNF alpha and 1 ng/ml IL-1 beta, while NCI-H292 cells were activated for 6 and 14 hours with the following cytokines: 5 ng/ml IL-4, 5 ng/ml IL-9, 5 ng/ml IL-13 and 25 ng/ml IFN gamma.

[0577] For these cell lines and blood cells, RNA was prepared by lysing approximately 107 cells/ml using Trizol (Gibco BRL). Briefly, {fraction (1/10)} volume of bromochloropropane (Molecular Research Corporation) was added to the RNA sample, vortexed and after 10 minutes at room temperature, the tubes were spun at 14,000 rpm in a Sorvall SS34 rotor. The aqueous phase was removed and placed in a 15 ml Falcon Tube. An equal volume of isopropanol was added and left at −20° C. overnight. The precipitated RNA was spun down at 9,000 rpm for 15 min in a Sorvall SS34 rotor and washed in 70% ethanol. The pellet was redissolved in 300 μl of RNase-free water and 35 μl buffer (Promega) 5 μl DTT, 7 μl RNAsin and 8 μl DNase were added. The tube was incubated at 37° C. for 30 minutes to remove contaminating genomic DNA, extracted once with phenol chloroform and re-precipitated with {fraction (1/10)} volume of 3M sodium acetate and 2 volumes of 100% ethanol. The RNA was spun down and placed in RNase free water. RNA was stored at −80° C.

[0578] AI_comprehensive panel_v1.0

[0579] The plates for AI_comprehensive panel_v1.0 include two control wells and 89 test samples comprised of cDNA isolated from surgical and postmortem human tissues obtained from the Backus Hospital and Clinomics (Frederick, Md.). Total RNA was extracted from tissue samples from the Backus Hospital in the Facility at CuraGen. Total RNA from other tissues was obtained from Clinomics.

[0580] 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.

[0581] 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.

[0582] 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.

[0583] 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.

[0584] In the labels employed to identify tissues in the AI_comprehensive panel_v.1.0 panel, the following abbreviations are used:

[0585] AI=Autoimmunity

[0586] Syn=Synovial

[0587] Normal=No apparent disease

[0588] Rep22/Rep20=individual patients

[0589] RA=Rheumatoid arthritis

[0590] Backus=From Backus Hospital

[0591] OA=Osteoarthritis

[0592] (SS) (BA) (MF)=Individual patients

[0593] Adj=Adjacent tissue

[0594] Match control=adjacent tissues

[0595] -M=Male

[0596] -F=Female

[0597] COPD=Chronic obstructive pulmonary disease

[0598] AI.05 Chondrosarcoma

[0599] The A1.05 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-1beta (10 ng/ml), IL-1beta+TNF-alpha (50 ng/ml), IL-1beta+Oncostatin (50 ng/ml) and PMA (100 ng/ml). The SW1353 cells were obtained from the 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 plates. 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.

[0600] Panels 5D and 5I

[0601] The plates for Panel 5D and 5I include two control wells and a variety of cDNAs isolated from human tissues and cell lines with an emphasis on metabolic diseases. Metabolic tissues were obtained from patients enrolled in the Gestational Diabetes study. Cells were obtained during different stages in the differentiation of adipocytes from human mesenchymal stem cells. Human pancreatic islets were also obtained.

[0602] In the Gestational Diabetes study subjects are young (18-40 years), otherwise healthy women with and without gestation al 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:

[0603] Patient 2: Diabetic Hispanic, overweight, not on insulin

[0604] Patient 7-9: Nondiabetic Caucasian and obese (BMI>30)

[0605] Patient 10: Diabetic Hispanic, overweight, on insulin

[0606] Patient 11: Nondiabetic African American and overweight

[0607] Patient 12: Diabetic Hispanic on insulin

[0608] 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:

[0609] Donor 2 and 3 U: Mesenchymal Stem cells, Undifferentiated Adipose

[0610] Donor 2 and 3 AM: Adipose, AdiposeMidway Differentiated

[0611] Donor 2 and 3 AD: Adipose, Adipose Differentiated

[0612] 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.

[0613] 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.

[0614] In the labels employed to identify tissues in the 5D and 5I panels, the following abbreviations are used:

[0615] GO Adipose=Greater Omentum Adipose

[0616] SK=Skeletal Muscle

[0617] UT=Uterus

[0618] PL=Placenta

[0619] AD=Adipose Differentiated

[0620] AM=Adipose Midway Differentiated

[0621] U=Undifferentiated Stem Cells

[0622] Panel CNSD.01

[0623] 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.

[0624] 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.

[0625] In the labels employed to identify tissues in the CNS panel, the following abbreviations are used:

[0626] PSP=Progressive supranuclear palsy

[0627] Sub Nigra=Substantia nigra

[0628] Glob Palladus=Globus palladus

[0629] Temp Pole=Temporal pole

[0630] Cing Gyr=Cingulate gyrus

[0631] BA 4=Brodman Area 4

[0632] Panel CNS_Neurodegeneration_V1.0

[0633] 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.

[0634] 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.

[0635] In the labels employed to identify tissues in the CNS_Neurodegeneration_V1.0 panel, the following abbreviations are used:

[0636] AD=Alzheimer's disease brain; patient was demented and showed AD-like pathology upon autopsy

[0637] Control=Control brains; patient not demented, showing no neuropathology

[0638] Control (Path)=Control brains; patient not demented but showing sever AD-like pathology

[0639] SupTemporal Ctx=Superior Temporal Cortex

[0640] Inf Temporal Ctx=Inferior Temporal Cortex

[0641] A. CG103827-03: Fibulin-2-Like Protein.

[0642] Expression of gene CG103827-03 was assessed using the primer-probe set Ag6712, described in Table AA. Results of the RTQ-PCR runs are shown in Tables AB, AC and AD.

TABLE AA
Probe Name Ag6712
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-cgctgtgaagacatcgacg-3′	19	2887	155
Probe	TET-5′-atcctctgcaccttccgctgtctcaa-3′-TAMRA	26	2926	156
Reverse	5′-ggtacccagtgcacactcat-3′	20	3032	157

[0643]

TABLE AB
CNS_neurodegeneration_v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag6712,		Ag6712,
	Run		Run
Tissue Name	276596839	Tissue Name	276596839
AD 1 Hippo	25.5	Control (Path) 3 Temporal Ctx	12.2
AD 2 Hippo	19.1	Control (Path) 4 Temporal Ctx	30.8
AD 3 Hippo	12.2	AD 1 Occipital Ctx	5.1
AD 4 Hippo	32.5	AD 2 Occipital Ctx (Missing)	0.0
AD 5 Hippo	28.3	AD 3 Occipital Ctx	7.2
AD 6 Hippo	100.0	AD 4 Occipital Ctx	29.9
Control 2 Hippo	50.7	AD 5 Occipital Ctx	33.9
Control 4 Hippo	18.4	AD 6 Occipital Ctx	22.7
Control (Path) 3 Hippo	19.5	Control 1 Occipital Ctx	38.7
AD 1 Temporal Ctx	12.2	Control 2 Occipital Ctx	48.6
AD 2 Temporal Ctx	22.4	Control 3 Occipital Ctx	11.3
AD 3 Temporal Ctx	3.5	Control 4 Occipital Ctx	14.6
AD 4 Temporal Ctx	25.2	Control (Path) 1 Occipital Ctx	24.1
AD 5 Inf Temporal Ctx	45.7	Control (Path) 2 Occipital Ctx	21.9
AD 5 Sup Temporal Ctx	67.8	Control (Path) 3 Occipital Ctx	7.9
AD 6 Inf Temporal Ctx	15.5	Control (Path) 4 Occipital Ctx	12.3
AD 6 Sup Temporal Ctx	81.2	Control 1 Parietal Ctx	21.9
Control 1 Temporal Ctx	19.3	Control 2 Parietal Ctx	26.2
Control 2 Temporal Ctx	4.7	Control 3 Parietal Ctx	7.7
Control 3 Temporal Ctx	20.4	Control (Path) 1 Parietal Ctx	61.1
Control 3 Temporal Ctx	15.0	Control (Path) 2 Parietal Ctx	52.5
Control (Path) 1 Temporal Ctx	40.1	Control (Path) 3 Parietal Ctx	3.4
Control (Path) 2 Temporal Ctx	20.3	Control (Path) 4 Parietal Ctx	22.1

[0644]

TABLE AC
General_screening_panel_v1.6
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag6712,		Ag6712,
	Run		Run
Tissue Name	277261484	Tissue Name	277261484
Adipose	5.5	Renal ca. TK-10	0.0
Melanoma* Hs688(A).T	34.4	Bladder	2.7
Melanoma* Hs688(B).T	33.0	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	0.1
Squamous cell carcinoma SCC-4	0.0	Colon ca.* (SW480 met) SW620	0.0
Testis Pool	11.1	Colon ca. HT29	0.1
Prostate ca.* (bone met) PC-3	0.1	Colon ca. HCT-116	0.0
Prostate Pool	3.1	Colon ca. CaCo-2	4.0
Placenta	8.9	Colon cancer tissue	10.6
Uterus Pool	1.5	Colon ca. SW1116	0.0
Ovarian ca. OVCAR-3	2.0	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	14.0	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	0.9	Colon Pool	3.8
Ovarian ca. OVCAR-5	0.0	Small Intestine Pool	1.6
Ovarian ca. IGROV-1	1.4	Stomach Pool	2.5
Ovarian ca. OVCAR-8	2.9	Bone Marrow Pool	2.7
Ovary	0.9	Fetal Heart	3.0
Breast ca. MCF-7	0.1	Heart Pool	3.5
Breast ca. MDA-MB-231	0.0	Lymph Node Pool	3.1
Breast ca. BT 549	100.0	Fetal Skeletal Muscle	1.9
Breast ca. T47D	0.0	Skeletal Muscle Pool	2.7
Breast ca. MDA-N	0.0	Spleen Pool	0.7
Breast Pool	3.1	Thymus Pool	3.0
Trachea	5.5	CNS cancer (glio/astro) U87-MG	0.1
Lung	0.5	CNS cancer (glio/astro) U-118-MG	0.4
Fetal Lung	5.7	CNS cancer (neuro; met) SK-N-AS	3.3
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-539	0.0
Lung ca. LX-1	0.2	CNS cancer (astro) SNB-75	0.2
Lung ca. NCI-H146	0.0	CNS cancer (glio) SNB-19	1.4
Lung ca. SHP-77	0.0	CNS cancer (glio) SF-295	16.0
Lung ca. A549	0.2	Brain (Amygdala) Pool	0.5
Lung ca. NCI-H526	0.0	Brain (cerebellum)	1.6
Lung ca. NCI-H23	6.6	Brain (fetal)	1.0
Lung ca. NCI-H460	0.0	Brain (Hippocampus) Pool	1.0
Lung ca. HOP-62	0.9	Cerebral Cortex Pool	0.9
Lung ca. NCI-H522	0.1	Brain (Substantia nigra) Pool	0.7
Liver	0.1	Brain (Thalamus) Pool	0.7
Fetal Liver	1.7	Brain (whole)	2.1
Liver ca. HepG2	0.0	Spinal Cord Pool	0.6
Kidney Pool	4.5	Adrenal Gland	1.4
Fetal Kidney	1.1	Pituitary gland Pool	0.1
Renal ca. 786-0	0.0	Salivary Gland	1.4
Renal ca. A498	0.1	Thyroid (female)	3.3
Renal ca. ACHN	0.0	Pancreatic ca. CAPAN2	0.0
Renal ca. UO-31	0.2	Pancreas Pool	1.0

[0645]

TABLE AD
Panel 4.1D
	Rel.		Rel.
	Ep. (%)		Exp. (%)
	Ag6712,		Ag6712,
	Run		Run
Tissue Name	276596876	Tissue Name	276596876
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 + 1L4	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 +	0.0
		IL-1beta
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 +	0.0
		IL1beta
Primary Th2 rest	0.0	Small airway epithelium none	0.0
Primary Tr1 rest	0.0	Small airway epithelium TNF alpha +	1.5
		IL-1beta
CD45RA CD4 lymphocyte act	15.0	Coronery artery SMC rest	13.4
CD45RO CD4 lymphocyte act	0.0	Coronery artery SMC TNF alpha +	14.5
		IL-1beta
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	12.1
CH11
LAK cells rest	0.0	CCD1106 (Keratinocytes)	6.1
		TNF alpha + IL-1beta
LAK cells IL-2	0.0	Liver cirrhosis	2.4
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	7.7
PBMC rest	0.0	Lung fibroblast TNF alpha + IL-1	0.5
		beta
PBMC PWM	0.0	Lung fibroblast IL-4	8.4
PBMC PHA-L	0.0	Lung fibroblast IL-9	4.7
Ramos (B cell) none	0.0	Lung fibroblast IL-13	3.6
Ramos (B cell) ionomycin	0.0	Lung fibroblast IFN gamma	16.0
B lymphocytes PWM	0.0	Dermal fibroblast CCD1070 rest	56.3
B lymphocytes CD40L and IL-4	0.0	Dermal fibroblast CCD1070 TNF	39.0
		alpha
EOL-1 dbcAMP	0.0	Dermal fibroblast CCD1070 IL-1	41.2
		beta
EOL-1 dbcAMP	0.0	Dermal fibroblast IFN gamma	51.8
PMA/ionomycin
Dendritic cells none	0.0	Dermal fibroblast IL-4	100.0
Dendritic cells LPS	0.0	Dermal Fibroblasts rest	52.5
Dendritic cells anti-CD40	0.0	Neutrophils TNFa + LPS	0.0
Monocytes rest	0.0	Neutrophils rest	0.0
Monocytes LPS	0.0	Colon	1.8
Macrophages rest	0.0	Lung	6.5
Macrophages LPS	0.0	Thymus	1.9
HUVEC none	0.0	Kidney	1.1
HUVEC starved	0.0

[0646] CNS_neurodegeneration_v1.0 Summary: Ag6712 This panel does not show differential expression of this gene in Alzheimer's disease. However, this profile confirms the expression of this gene at low levels in the brain. Please see Panel 1.6 for discussion of utility of this gene in the central nervous system.

[0647] General_screening_panel_v1.6 Summary: Ag6712 Highest expression of this gene is seen in a breast cancer cell line (CT=26.4). Moderate levels of expression are also seen in brain, melanoma, and ovarian cancer cell lines. Thus, expression of this gene could be used to differentiate between these samples and other samples on this panel and as a marker 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 breast, brain, melanoma, and ovarian cancers.

[0648] Low but significant levels of expression are seen in pancreas, adrenal, thyroid, adult and fetal skeletal muscle and heart, fetal liver, and adipose. 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.

[0649] This gene is also expressed at low levels in the CNS, including the hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therefore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of neurological disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.

[0650] In addition, this gene is expressed at much higher levels in fetal lung and liver tissue (CTs=30.5-32.5) when compared to expression in the adult counterpart (CTs=34-35). Thus, expression of this gene may be used to differentiate between the fetal and adult source of these tissues. Furthermore, the relative overexpression of this gene in fetal tissue suggests that the protein product may enhance organ growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the GPCR encoded by this gene could be useful in treatment of lung or liver related diseases.

[0651] Panel 4.1D Summary: Ag6712 Expression of this gene is most prominent in a cluster sf samples derived from dermal fibroblasts, with highest expression in IL-4 treated dermal fibroblasts (CT=32.3). Thus, expression of this gene could be used as a marker of this cell type and to differentiate between these samples and other samples on this panel. This expression also suggests that this gene product may be involved in inflammatory conditions of the skin, including psoriasis.

[0652] B. CG105716-01, CG105716-02, CG105716-03, CG105716-04, CG105716-05 and CG105716-06: Cartilage Oligomeric Matrix Protein Precursor-Like Protein.

[0653] Expression of gene CG105716-01, CG105716-02, CG105716-03, CG105716-04, CG105716-05, and CG105716-06 was assessed using the primer-probe sets Ag2362, Ag5922, Ag5924, Ag5928, Ag5936 and Ag6846, described in Tables BA, BB, BC, BD, BE and BF. Results of the RTQ-PCR runs are shown in Tables BG, BH, BI, BJ, BK, BL, BM, BN, BO, BP and BQ. Please note that probe-primer sets Ag5922 is specific for CG105716-03, Ag5924 is specific for CG105716-04, Ag5928 is specific for CG105716-05 and Ag5936 is specific for CG105716-06.

TABLE BA
Probe Name Ag2362
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-gtataggggatgcctgtgaca-3′	21	1230	158
Probe	TET-5′-actgtccccagaagagcaacccg-3′-TAMRA	23	1251	159
Reverse	5′-cacaagcatctcccacaaa-3′	19	1298	160

[0654]

TABLE RB
Probe Name Ag5922
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-gactctcgggacaactgccg-3′	20	1352	161
Probe	TET-5′-tctgcatcaaagtcgtcctggcacagcgt-3′-TAMRA	28	1422	162
Reverse	5′-cggacacacgtcgatcttgt-3′	20	1461	163

[0655]

TABLE BC
Probe Name Ag5924
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-gactttgtgggagatgcttgt-3′	21	1295	164
Probe	TET-5′-atgtccgtctccatcctggtcttgat-3′-TAMRA	26	1323	165
Reverse	5′-tggtctgagtcccgagagt-3′	19	1362	166

[0656]

TABLE BD
Probe Name Ag5928
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-ctgacagtcgggacggcgt-3′	19	1458	1167
Probe	TET-5′-tccagcacgactgtctggaaggccctga-3′-TAMRA	28	1569	1168
Reverse	5′-cttccctggttgagcaccac-3′	20	1631	1169

[0657]

TABLE BE
Probe Name Ag5936
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-ctgcgacgacgacgtgtgc-3′	19	1426	170
Probe	TET-5′-agaacgctgaagtcacgctcaccgacttca-3′-TAMRA	30	1497	171
Reverse	5′-tctcccttccctggttgagc-3′	20	1591	172

[0658]

TABLE BF
Probe Name Ag6846
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-aacataactgcgtccccaact-3′	21	588	173
Probe	TET-5′-ccttccagtgcggcccgtgcca-3′-TAMRA	22	633	174
Reverse	5′-cctggtcgcccacgaa-3′	16	662	175

[0659]

TABLE BG
AI.05 chondrosarcoma
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag2362,		Ag2362,
	Run		Run
Tissue Name	316264541	Tissue Name	316264541
138353_PMA (18hrs)	0.3	138346_IL-1beta + Oncostatin M	0.2
		(6hrs)
138352_IL-1beta + Oncostatin M	0.5	138345_IL-1beta + TNFa (6hrs)	0.1
(18hrs)
138351_IL-1beta + TNFa (18hrs)	6.6	138344_IL-1beta (6hrs)	0.1
138350_IL-1beta (18hrs)	1.1	138349_Untreated-serum starved	68.8
		(6hrs)
138354_Untreated-complete	0.0	138348_Untreated-complete	100.0
medium (18hrs)		medium (6hrs)
138347_PMA (6hrs)	0.7

[0660]

TABLE BH
AI_comprehensive panel_v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag2362,		Ag2362,
	Run		Run
Tissue Name	255325334	Tissue Name	255325334
110967 COPD-F	0.0	112427 Match Control Psoriasis-F	0.0
110980 COPD-F	0.0	112418 Psoriasis-M	0.0
110968 COPD-M	0.0	112723 Match Control Psoriasis-M	0.0
110977 COPD-M	0.0	112419 Psoriasis-M	0.0
110989 Emphysema-F	0.0	112424 Match Control Psoriasis-M	0.0
110992 Emphysema-F	0.3	112420 Psoriasis-M	0.0
110993 Emphysema-F	0.0	112425 Match Control Psoriasis-M	0.0
110994 Emphysema-F	0.0	104689 (MF) OA Bone-Backus	1.2
110995 Emphysema-F	0.4	104690 (MF) Adj “Normal”	2.0
		Bone-Backus
110996 Emphysema-F	0.1	104691 (MF) OA Synovium-Backus	2.0
110997 Asthma-M	0.0	104692 (BA) OA Cartilage-Backus	100.0
111001 Asthma-F	0.0	104694 (BA) OA Bone-Backus	2.0
111002 Asthma-F	0.0	104695 (BA) Adj “Normal”	7.1
		Bone-Backus
111003 Atopic Asthma-F	0.0	104696 (BA) OA Synovium-Backus	2.0
111004 Atopic Asthma-F	0.0	104700 (SS) OA Bone-Backus	1.8
111005 Atopic Asthma-F	0.0	104701 (SS) Adj “Normal”	7.0
		Bone-Backus
111006 Atopic Asthma-F	0.0	104702 (SS) OA Synovium-Backus	13.0
111417 Allergy-M	0.0	117093 OA Cartilage Rep7	0.0
112347 Allergy-M	0.0	112672 OA Bone5	0.0
112349 Normal Lung-F	0.0	112673 OA Synovium5	0.0
112357 Normal Lung-F	0.0	112674 OA Synovial Fluid cells5	0.0
112354 Normal Lung-M	0.0	117100 OA Cartilage Rep 14	0.0
112374 Crohns-F	0.1	112756 OA Bone9	0.0
112389 Match Control Crohns-F	1.1	112757 OA Synovium9	0.0
112375 Crohns-F	0.0	112758 OA Synovial Fluid Cells9	0.0
112732 Match Control Crohns-F	0.0	117125 RA Cartilage Rep2	0.0
112725 Crohns-M	0.0	113492 Bone2 RA	0.0
112387 Match Control	0.0	113493 Synovium2 RA	0.0
Crohns-M
112378 Crohns-M	0.0	113494 Syn Fluid Cells RA	0.0
112390 Match Control	0.0	113499 Cartilage4 RA	0.0
Crohns-M
112726 Crohns-M	0.0	113500 Bone4 RA	0.0
112731 Match Control	0.0	113501 Synovium4 RA	0.0
Crohns-M
112380 Ulcer Col-F	0.0	113502 Syn Fluid Cells4 RA	0.0
112734 Match Control Ulcer	0.0	113495 Cartilage3 RA	0.0
Col-F
112384 Ulcer Col-F	0.1	113496 Bone3 RA	0.0
112737 Match Control Ulcer	0.0	113497 Synovium3 RA	0.0
Col-F
112386 Ulcer Col-F	0.2	113498 Syn Fluid Cells3 RA	0.0
112738 Match Control Ulcer	0.0	117106 Normal Cartilage Rep20	0.0
Col-F
112381 Ulcer Col-M	0.0	113663 Bone3 Normal	0.0
112735 Match Control Ulcer	0.0	113664 Synovium3 Normal	0.0
Col-M
112382 Ulcer Col-M	0.2	113665 Syn Fluid Cells3 Normal	0.0
112394 Match Control Ulcer	0.0	117107 Normal Cartilage Rep22	0.0
Col-M
112383 Ulcer Col-M	0.1	113667 Bone4 Normal	0.0
112736 Match Control Ulcer	0.3	113668 Synovium4 Normal	0.0
Col-M
112423 Psoriasis-F	0.0	113669 Syn Fluid Cells4 Normal	0.0

[0661]

TABLE BI
General_screening_panel_v1.5
	Rel.	Rel.	Rel.	Rel.	Rel.
	Exp. (%)	Exp. (%)	Exp. (%)	Exp. (%)	Exp. (%)
	Ag2362,	Ag5922,	Ag5924,	Ag5928,	Ag5936,
	Run	Run	Run	Run	Run
Tissue Name	248156467	247608955	247608957	247834910	248102147
Adipose	1.7	0.4	0.3	0.3	0.7
Melanoma* Hs688(A).T	100.0	100.0	100.0	100.0	100.0
Melanoma* Hs688(B).T	81.2	85.9	76.3	81.2	80.7
Melanoma* M14	0.0	0.0	0.0	0.0	0.0
Melanoma* LOXIMVI	0.0	0.0	0.0	0.0	0.0
Melanoma* SK-MEL-5	0.0	0.0	0.0	0.0	0.0
Squamous cell	0.0	0.0	0.0	0.0	0.0
carcinoma SCC-4
Testis Pool	3.2	2.0	1.8	1.1	1.2
Prostate ca.*	0.0	0.0	0.0	0.0	0.0
(bone met) PC-3
Prostate Pool	1.0	0.4	0.3	0.2	0.0
Placenta	0.6	0.8	0.3	0.8	0.6
Uterus Pool	0.0	0.1	0.0	0.0	0.0
Ovarian ca. OVCAR-3	0.0	0.0	0.0	0.0	0.0
Ovarian ca. SK-OV-3	0.0	0.0	0.0	0.0	0.0
Ovarian ca. OVCAR-4	0.0	0.0	0.0	0.0	0.0
Ovarian ca. OVCAR-5	0.1	0.0	0.0	0.0	0.0
Ovarian ca. IGROV-1	0.0	0.0	0.0	0.0	0.0
Ovarian ca. OVCAR-8	0.0	0.0	0.0	0.0	0.0
Ovary	0.5	0.0	0.4	0.0	0.0
Breast ca. MCF-7	0.0	0.0	0.0	0.0	0.0
Breast ca. MDA-MB-231	0.0	0.0	0.0	0.0	0.0
Breast ca. BT 549	0.0	0.0	0.0	0.0	0.0
Breast ca. T47D	0.0	0.0	0.0	0.0	0.0
Breast ca. MDA-N	0.0	0.0	0.0	0.0	0.0
Breast Pool	0.1	0.0	0.0	0.0	0.0
Trachea	4.1	3.1	2.2	2.2	5.4
Lung	0.1	0.0	0.0	0.0	0.0
Fetal Lung	0.0	0.0	0.0	0.0	0.0
Lung ca. NCI-N417	0.0	0.0	0.0	0.0	0.0
Lung ca. LX-1	0.4	0.2	0.2	0.1	0.0
Lung ca. NCI-H146	0.0	0.0	0.0	0.0	0.0
Lung ca. SHP-77	0.0	0.0	0.0	0.0	0.0
Lung ca. A549	0.0	0.0	0.0	0.0	0.0
Lung ca. NCI-H526	0.0	0.0	0.0	0.0	0.0
Lung ca. NCI-H23	0.1	0.0	0.0	0.0	0.0
Lung ca. NCI-H460	0.0	0.0	0.0	0.0	0.0
Lung ca. HOP-62	0.0	0.0	0.0	0.0	0.0
Lung ca. NCI-H522	0.0	0.0	0.0	0.0	0.0
Liver	0.0	0.0	0.0	0.0	0.0
Fetal Liver	0.0	0.0	0.0	0.0	0.0
Liver ca. HepG2	0.8	0.9	0.7	0.7	0.5
Kidney Pool	0.2	0.1	0.1	0.0	0.0
Fetal Kidney	0.0	0.0	0.0	0.0	0.0
Renal ca. 786-0	0.0	0.0	0.0	0.0	0.0
Renal ca. A498	0.0	0.1	0.0	0.0	0.0
Renal ca. ACHN	0.0	0.0	0.0	0.0	0.0
Renal ca. UO-31	0.0	0.0	0.0	0.0	0.0
Renal ca. TK-10	0.4	0.1	0.2	0.0	0.3
Bladder	7.5	3.5	5.0	3.7	6.6
Gastric ca.	0.0	0.0	0.0	0.0	0.0
(liver met.) NCI-N87
Gastric ca. KATO III	0.0	0.0	0.0	0.0	0.0
Colon ca. SW-948	0.0	0.0	0.0	0.0	0.0
Colon ca. SW480	0.0	0.1	0.0	0.0	0.0
Colon ca.*	0.0	0.0	0.0	0.0	0.0
(SW480 met) SW620
Colon ca. HT29	0.0	0.0	0.0	0.0	0.0
Colon ca. HCT-116	0.0	0.0	0.0	0.0	0.0
Colon ca. CaCo-2	0.1	0.0	0.0	0.0	0.0
Colon cancer tissue	16.6	14.2	18.2	16.2	20.9
Colon ca. SW1116	0.0	0.0	0.0	0.0	0.0
Colon ca. Colo-205	0.0	0.0	0.0	0.0	0.0
Colon ca. SW-48	0.0	0.0	0.0	0.0	0.0
Colon Pool	0.2	0.0	0.0	0.0	0.1
Small Intestine Pool	0.0	0.0	0.0	0.0	0.0
Stomach Pool	0.5	0.3	0.2	0.1	0.0
Bone Marrow Pool	0.2	0.0	0.0	0.0	0.0
Fetal Heart	0.1	0.0	0.1	0.0	0.0
Heart Pool	0.0	0.1	0.0	0.0	0.0
Lymph Node Pool	0.0	0.0	0.0	0.0	0.0
Fetal Skeletal Muscle	0.7	0.2	0.3	0.3	0.0
Skeletal Muscle Pool	0.2	0.1	0.2	0.1	0.0
Spleen Pool	0.0	0.1	0.0	0.0	0.0
Thymus Pool	0.1	0.0	0.0	0.0	0.0
CNS cancer	0.0	0.0	0.0	0.0	0.0
(glio/astro) U87-MG
CNS cancer	0.6	0.6	0.3	0.4	0.7
(glio/astro) U-118-MG
CNS cancer	0.0	0.0	0.0	0.0	0.0
(neuro; met) SK-N-AS
CNS cancer (astro) SF-539	0.0	0.0	0.0	0.0	0.0
CNS cancer (astro) SNB-75	0.0	0.1	0.0	0.0	0.0
CNS cancer (glio) SNB-19	0.0	0.1	0.0	0.0	0.0
CNS cancer (glio) SF-295	0.0	0.0	0.0	0.0	0.0
Brain (Amygdala) Pool	0.0	0.0	0.0	0.0	0.0
Brain (cerebellum)	1.4	0.6	1.1	0.4	0.9
Brain (fetal)	0.0	0.0	0.0	0.0	0.0
Brain (Hippocampus) Pool	0.1	0.0	0.0	0.0	0.0
Cerebral Cortex Pool	0.0	0.0	0.0	0.0	0.0
Brain (Substantia	0.0	0.0	0.0	0.0	0.0
nigra) Pool
Brain (Thalamus) Pool	0.0	0.0	0.0	0.0	0.0
Brain (whole)	0.0	0.0	0.0	0.0	0.0
Spinal Cord Pool	0.0	0.1	0.0	0.0	0.2
Adrenal Gland	0.0	0.0	0.0	0.0	0.0
Pituitary gland Pool	0.0	0.0	0.0	0.0	0.0
Salivary Gland	0.1	0.0	0.0	0.0	0.0
Thyroid (female)	0.3	0.2	0.7	0.2	0.0
Pancreatic ca. CAPAN2	0.0	0.0	0.0	0.0	0.0
Pancreas Pool	7.4	6.7	5.8	5.1	6.9

[0662]

TABLE BJ
General_screening_panel_v1.6
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag6846,		Ag6846,
	Run		Run
Tissue Name	278391621	Tissue Name	278391621
Adipose	0.2	Renal ca. TK-10	0.1
Melanoma* Hs688(A).T	100.0	Bladder	2.1
Melanoma* Hs688(B).T	92.0	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	2.1	Colon ca. HT29	0.0
Prostate ca.* (bone met) PC-3	0.0	Colon ca. HCT-116	0.0
Prostate Pool	0.2	Colon ca. CaCo-2	0.1
Placenta	0.3	Colon cancer tissue	9.1
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	0.1
Ovarian ca. OVCAR-5	0.0	Small Intestine Pool	0.0
Ovarian ca. IGROV-1	0.0	Stomach Pool	0.6
Ovarian ca. OVCAR-8	0.0	Bone Marrow Pool	0.0
Ovary	0.1	Fetal Heart	0.0
Breast ca. MCF-7	0.0	Heart Pool	0.0
Breast ca. MDA-MB-231	0.0	Lymph Node Pool	0.0
Breast ca. BT 549	0.0	Fetal Skeletal Muscle	0.1
Breast ca. T47D	0.0	Skeletal Muscle Pool	0.0
Breast ca. MDA-N	0.0	Spleen Pool	0.0
Breast Pool	0.0	Thymus Pool	0.1
Trachea	1.4	CNS cancer (glio/astro) U87-MG	0.0
Lung	0.0	CNS cancer (glio/astro) U-118-MG	0.2
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	0.0
Lung ca. NCI-H526	0.0	Brain (cerebellum)	0.7
Lung ca. NCI-H23	0.0	Brain (fetal)	0.0
Lung ca. NCI-H460	0.0	Brain (Hippocampus) Pool	0.1
Lung ca. HOP-62	0.0	Cerebral Cortex Pool	0.0
Lung ca. NCI-H522	0.0	Brain (Substantia nigra) Pool	0.0
Liver	0.0	Brain (Thalamus) Pool	0.0
Fetal Liver	0.0	Brain (whole)	0.0
Liver ca. HepG2	0.3	Spinal Cord Pool	0.0
Kidney Pool	0.2	Adrenal Gland	0.0
Fetal Kidney	0.0	Pituitary gland Pool	0.0
Renal ca. 786-0	0.0	Salivary Gland	0.0
Renal ca. A498	0.0	Thyroid (female)	0.2
Renal ca. ACHN	0.0	Pancreatic ca. CAPAN2	0.0
Renal ca. UO-31	0.0	Pancreas Pool	0.1

[0663]

TABLE BK
HASS Panel v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag2362,		Ag2362,
	Run		Run
Tissue Name	268623699	Tissue Name	268623699
MCF-7 C1	0.0	U87-MG F1 (B)	0.0
MCF-7 C2	0.2	U87-MG F2	0.0
MCF-7 C3	0.4	U87-MG F3	0.0
MCF-7 C4	0.6	U87-MG F4	0.0
MCF-7 C5	0.6	U87-MG F5	0.0
MCF-7 C6	0.3	U87-MG F6	0.0
MCF-7 C7	0.0	U87-MG F7	0.0
MCF-7 C9	0.0	U87-MG F8	0.0
MCF-7 C10	0.0	U87-MG F9	0.1
MCF-7 C11	0.0	U87-MG F10	0.0
MCF-7 C12	0.0	U87-MG F11	0.0
MCF-7 C13	0.1	U87-MG F12	0.0
MCF-7 C15	0.0	U87-MG F13	0.0
MCF-7 C16	0.3	U87-MG F14	0.0
MCF-7 C17	0.0	U87-MG F15	0.0
T24 D1	0.0	U87-MG F16	0.0
T24 D2	0.2	U87-MG F17	0.4
T24 D3	0.5	LnCAP A1	0.4
T24 D4	0.0	LnCAP A2	0.0
T24 D5	0.2	LnCAP A3	0.8
T24 D6	0.0	LnCAP A4	0.5
T24 D7	0.0	LnCAP A5	0.7
T24 D9	0.0	LnCAP A6	0.3
T24 D10	0.3	LnCAP A7	2.0
T24 D11	0.0	LnCAP A8	4.9
T24 D12	0.3	LnCAP A9	2.4
T24 D13	0.3	LnCAP A10	2.6
T24 D15	0.0	LnCAP A11	6.7
T24 D16	0.9	LnCAP A12	0.3
T24 D17	0.0	LnCAP A13	0.7
CAPaN B1	0.0	LnCAP A14	1.4
CAPaN B2	0.0	LnCAP A15	3.0
CAPaN B3	0.0	LnCAP A16	0.3
CAPaN B4	0.0	LnCAP A17	5.5
CAPaN B5	0.3	Primary Astrocytes	100.0
CAPaN B6	0.0	Primary Renal Proximal	0.0
		Tubule Epithelial cell A2
CAPaN B7	0.1	Primary melanocytes A5	0.0
CAPaN B8	0.0	126443 - 341 medullo	0.5
CAPaN B9	0.0	126444 - 487 medullo	0.0
CAPaN B10	0.0	126445 - 425 medullo	0.0
CAPaN B11	0.0	126446 - 690 medullo	1.2
CAPaN B12	0.0	126447 - 54 adult glioma	0.0
CAPaN B13	0.0	126448 - 245 adult glioma	0.3
CAPaN B14	0.3	126449 - 317 adult glioma	0.0
CAPaN B15	0.0	126450 - 212 glioma	0.0
CAPaN B16	0.0	126451 - 456 glioma	0.0
CAPaN B17	0.0

[0664]

TABLE BL
Panel 1.3D
	Rel.	Rel.		Rel.	Rel.
	Exp. (%)	Exp. (%)		Exp. (%)	Exp. (%)
	Ag2362,	Ag2362,		Ag2362,	Ag2362,
	Run	Run		Run	Run
Tissue Name	166013008	167966893	Tissue Name	166013008	167966893
Liver	0.3	1.2	Kidney (fetal)	0.0	2.8
adenocarcinoma
Pancreas	0.5	0.6	Renal ca. 786-0	0.0	0.0
Pancreatic ca.	0.0	0.0	Renal ca. A498	0.0	0.1
CAPAN 2
Adrenal gland	0.3	0.0	Renal ca. RXF 393	0.0	0.0
Thyroid	0.5	1.5	Renal ca. ACHN	0.0	0.2
Salivary gland	1.8	0.2	Renal ca. UO-31	0.0	0.0
Pituitary gland	0.0	0.0	Renal ca. TK-10	0.0	0.0
Brain (fetal)	0.0	0.0	Liver	0.0	0.0
Brain (whole)	0.2	1.4	Liver (fetal)	0.0	0.0
Brain (amygdala)	0.0	0.0	Liver ca.	6.4	9.5
			(hepatoblast) HepG2
Brain (cerebellum)	5.4	4.6	Lung	0.9	1.6
Brain (hippocampus)	0.0	0.2	Lung (fetal)	2.2	5.3
Brain (substantia	1.6	0.9	Lung ca. (small cell)	1.6	2.0
nigra)			LX-1
Brain (thalamus)	0.0	0.0	Lung ca. (small cell)	0.0	0.0
			NCI-H69
Cerebral Cortex	0.0	0.0	Lung ca. (s.cell var.)	0.0	0.0
			SHP-77
Spinal cord	0.6	0.6	Lung ca. (large	0.4	0.0
			cell)NCI-H460
glio/astro U87-MG	0.0	0.0	Lung ca. (non-sm.	0.0	0.3
			cell) A549
glio/astro U-118-MG	2.3	1.6	Lung ca. (non-s.cell)	0.0	0.4
			NCI-H23
astrocytoma	0.0	0.0	Lung ca. (non-s.cell)	0.0	0.0
SW1783			HOP-62
neuro*; met	0.0	0.1	Lung ca. (non-s.cl)	0.0	0.3
SK-N-AS			NCI-H522
astrocytoma SF-539	0.0	0.0	Lung ca. (squam.)	0.0	0.0
			SW 900
astrocytoma SNB-75	0.0	0.3	Lung ca. (squam.)	0.0	0.3
			NCI-H596
glioma SNB-19	0.0	0.0	Mammary gland	2.8	1.4
glioma U251	0.0	0.0	Breast ca.* (pl.ef)	0.0	0.0
			MCF-7
glioma SF-295	0.3	0.0	Breast ca.* (pl.ef)	0.0	0.0
			MDA-MB-231
Heart (fetal)	5.4	16.5	Breast ca.* (pl.ef)	0.0	0.0
			T47D
Heart	4.9	12.9	Breast ca. BT-549	0.0	0.0
Skeletal muscle	22.7	69.7	Breast ca. MDA-N	0.0	0.0
(fetal)
Skeletal muscle	35.4	52.5	Ovary	0.2	1.5
Bone marrow	6.4	11.2	Ovarian ca.	0.0	0.0
			OVCAR-3
Thymus	0.0	0.2	Ovarian ca.	0.0	0.0
			OVCAR-4
Spleen	0.3	0.0	Ovarian ca.	0.0	0.0
			OVCAR-5
Lymph node	0.3	0.0	Ovarian ca.	0.0	0.0
			OVCAR-8
Colorectal	0.0	0.2	Ovarian ca.	0.0	0.0
			IGROV-1
Stomach	1.2	0.6	Ovarian ca.*	0.0	0.0
			(ascites) SK-OV-3
Small intestine	0.0	0.7	Uterus	1.3	2.6
Colon ca. SW480	0.0	0.0	Placenta	20.3	1.2
Colon ca.*	0.3	1.5	Prostate	1.8	2.7
SW620 (SW480 met)
Colon ca. HT29	0.0	0.0	Prostate ca.* (bone	0.0	0.0
			met) PC-3
Colon ca. HCT-116	0.0	0.0	Testis	17.6	21.9
Colon ca. CaCo-2	0.0	0.0	Melanoma	68.8	91.4
			Hs688(A).T
Colon ca.	100.0	99.3	Melanoma* (met)	71.7	100.0
tissue(ODO3866)			Hs688(B).T
Colon ca. HCC-2998	0.0	0.0	Melanoma	0.0	0.0
			UACC-62
Gastric ca.* (liver	0.3	0.0	Melanoma M14	0.0	0.0
met) NCI-N87
Bladder	31.9	45.7	Melanoma LOX	0.0	0.0
			IMVI
Trachea	7.8	14.1	Melanoma* (met)	0.0	0.0
			SK-MEL-5
Kidney	0.3	0.7	Adipose	11.7	28.1

[0665]

TABLE BM
Panel 2D
	Rel.		Rel.
	Ex. (%)		Exp. (%)
	Ag2362,		Ag2362,
	Run		Run
Tissue Name	164151688	Tissue Name	164151688
Normal Colon	1.2	Kidney Margin 8120608	0.8
CC Well to Mod Diff (ODO3866)	54.0	Kidney Cancer 8120613	0.0
CC Margin (ODO3866)	0.9	Kidney Margin 8120614	0.9
CC Gr.2 rectosigmoid (ODO3868)	3.2	Kidney Cancer 9010320	12.8
CC Margin (ODO3868)	0.2	Kidney Margin 9010321	0.8
CC Mod Diff (ODO3920)	0.4	Normal Uterus	2.9
CC Margin (ODO3920)	0.3	Uterus Cancer 064011	0.9
CC Gr.2 ascend colon (ODO3921)	11.5	Normal Thyroid	1.7
CC Margin (ODO3921)	9.4	Thyroid Cancer 064010	1.4
CC from Partial Hepatectomy	46.3	Thyroid Cancer A302152	22.8
(ODO4309) Mets
Liver Margin (ODO4309)	0.0	Thyroid Margin A302153	0.3
Colon mets to lung (OD04451-01)	2.2	Normal Breast	2.6
Lung Margin (OD04451-02)	0.1	Breast Cancer (OD04566)	21.9
Normal Prostate 6546-1	12.0	Breast Cancer (OD04590-01)	73.2
Prostate Cancer (OD04410)	36.6	Breast Cancer Mets	100.0
		(OD04590-03)
Prostate Margin (OD04410)	18.2	Breast Cancer Metastasis	9.9
		(OD04655-05)
Prostate Cancer (OD04720-01)	11.9	Breast Cancer 064006	35.8
Prostate Margin (OD04720-02)	2.3	Breast Cancer 1024	21.5
Normal Lung 061010	5.4	Breast Cancer 9100266	44.4
Lung Met to Muscle (ODO4286)	5.7	Breast Margin 9100265	21.3
Muscle Margin (ODO4286)	19.6	Breast Cancer A209073	44.4
Lung Malignant Cancer (OD03126)	16.0	Breast Margin A209073	4.9
Lung Margin (OD03126)	4.5	Normal Liver	0.0
Lung Cancer (OD04404)	5.2	Liver Cancer 064003	0.0
Lung Margin (OD04404)	10.7	Liver Cancer 1025	0.0
Lung Cancer (OD04565)	22.5	Liver Cancer 1026	2.9
Lung Margin (OD04565)	1.0	Liver Cancer 6004-T	0.0
Lung Cancer (OD04237-01)	15.5	Liver Tissue 6004-N	0.5
Lung Margin (OD04237-02)	12.2	Liver Cancer 6005-T	3.3
Ocular Mel Met to Liver	0.3	Liver Tissue 6005-N	0.0
(ODO4310)
Liver Margin (ODO4310)	0.0	Normal Bladder	52.5
Melanoma Mets to Lung	0.1	Bladder Cancer 1023	20.9
(OD04321)
Lung Margin (OD04321)	0.6	Bladder Cancer A302173	19.1
Normal Kidney	0.8	Bladder Cancer (OD04718-01)	5.2
Kidney Ca, Nuclear grade 2	1.1	Bladder Normal Adjacent	34.9
(OD04338)		(OD04718-03)
Kidney Margin (OD04338)	3.4	Normal Ovary	0.6
Kidney Ca Nuclear grade 1/2	0.1	Ovarian Cancer 064008	71.2
(OD04339)
Kidney Margin (OD04339)	1.3	Ovarian Cancer (OD04768-07)	0.6
Kidney Ca, Clear cell type	0.3	Ovary Margin (OD04768-08)	19.2
(OD04340)
Kidney Margin (OD04340)	2.5	Normal Stomach	0.3
Kidney Ca, Nuclear grade 3	2.9	Gastric Cancer 9060358	4.0
(OD04348)
Kidney Margin (OD04348)	0.7	Stomach Margin 9060359	1.0
Kidney Cancer (OD04622-01)	3.7	Gastric Cancer 9060395	4.1
Kidney Margin (OD04622-03)	0.2	Stomach Margin 9060394	2.5
Kidney Cancer (OD04450-01)	0.0	Gastric Cancer 9060397	84.1
Kidney Margin (OD04450-03)	2.5	Stomach Margin 9060396	0.9
Kidney Cancer 8120607	16.8	Gastric Cancer 064005	1.1

[0666]

TABLE BN
Panel 3D
	Rel.		Rel.
	Ex. (%)		Exp. (%)
	Ag2362,		Ag2362,
	Run		Run
Tissue Name	168032574	Tissue Name	168032574
Daoy-Medulloblastoma	0.0	Ca Ski-Cervical epidermoid	0.0
		carcinoma (metastasis)
TE671-Medulloblastoma	8.0	ES-2-Ovarian clear cell carcinoma	0.0
D283 Med-Medulloblastoma	0.6	Ramos-Stimulated with	0.0
		PMA/ionomycin 6h
PFSK-1-Primitive	0.0	Ramos-Stimulated with	0.6
Neuroectodermal		PMA/ionomycin 14h
XF-498-CNS	0.0	MEG-01-Chronic myelogenous	0.0
		leukemia (megokaryoblast)
SNB-78-Glioma	2.2	Raji-Burkitt's lymphoma	0.0
SF-268-Glioblastoma	0.0	Daudi-Burkitt's lymphoma	0.0
T98G-Glioblastoma	0.0	U266-B-cell plasmacytoma	0.7
SK-N-SH-Neuroblastoma	12.6	CA46-Burkitt's lymphoma	0.0
(metastasis)
SF-295-Glioblastoma	0.0	RL-non-Hodgkin's B-cell	0.0
		lymphoma
Cerebellum	31.6	JM1-pre-B-cell lymphoma	0.0
Cerebellum	100.0	Jurkat-T cell leukemia	0.0
NCI-H292-Mucoepidermoid	0.0	TF-1-Erythroleukemia	0.0
lung carcinoma
DMS-114-Small cell lung	57.0	HUT 78-T-cell lymphoma	0.0
cancer
DMS-79-Small cell lung cancer	29.7	U937-Histiocytic lymphoma	0.0
NCI-H146-Small cell lung	6.7	KU-812-Myelogenous leukemia	0.7
cancer
NCI-H526-Small cell lung	0.0	769-P-Clear cell renal carcinoma	0.0
cancer
NCI-N417-Small cell lung	0.0	Caki-2-Clear cell renal carcinoma	0.0
cancer
NCI-H82-Small cell lung cancer	0.0	SW 839-Clear cell renal carcinoma	0.0
NCI-H157-Squamous cell lung	0.0	Rhabdoid kidney tumor	2.3
cancer (metastasis)
NCI-H1155-Large cell lung	0.5	Hs766T-Pancreatic carcinoma (LN	0.6
cancer		metastasis)
NCI-H1299-Large cell lung	0.7	CAPAN-1-Pancreatic	0.0
cancer		adenocarcinoma (liver metastasis)
NCI-H727-Lung carcinoid	85.9	SU86.86-Pancreatic carcinoma	1.4
		(liver metastasis)
NCI-UMC-11-Lung carcinoid	0.0	BxPC-3-Pancreatic	2.7
		adenocarcinoma
LX-1-Small cell lung cancer	11.5	HPAC-Pancreatic adenocarcinoma	0.0
Colo-205-Colon cancer	0.0	MIA PaCa-2-Pancreatic carcinoma	0.0
KM12-Colon cancer	0.0	CFPAC-1-Pancreatic ductal	0.0
		adenocarcinoma
KM20L2-Colon cancer	0.0	PANC-1-Pancreatic epithelioid	6.2
		ductal carcinoma
NCI-H716-Colon cancer	9.5	T24-Bladder carcinma (transitional	0.0
		cell)
SW-48-Colon adenocarcinoma	0.0	5637-Bladder carcinoma	0.0
SW1116-Colon adenocarcinoma	0.0	HT-1197-Bladder carcinoma	0.0
LS 174T-Colon adenocarcinoma	0.0	UM-UC-3-Bladder carcinma	0.0
		(transitional cell)
SW-948-Colon adenocarcinoma	0.0	A204-Rhabdomyosarcoma	2.4
SW-480-Colon adenocarcinoma	0.0	HT-1080-Fibrosarcoma	0.0
NCI-SNU-5-Gastric carcinoma	1.4	MG-63-Osteosarcoma	14.1
KATO III-Gastric carcinoma	0.0	SK-LMS-1-Leiomyosarcoma	0.0
		(vulva)
NCI-SNU-16-Gastric carcinoma	0.0	SJRH30-Rhabdomyosarcoma (met	0.0
		to bone marrow)
NCI-SNU-1-Gastric carcinoma	0.0	A431-Epidermoid carcinoma	0.0
RF-1-Gastric adenocarcinoma	0.0	WM266-4-Melanoma	0.5
RF-48-Gastric adenocarcinoma	4.5	DU 145-Prostate carcinoma (brain	0.0
		metastasis)
MKN-45-Gastric carcinoma	0.0	MDA-MB-468-Breast	0.0
		adenocarcinoma
NCI-N87-Gastric carcinoma	0.0	SCC-4-Squamous cell carcinoma of	0.0
		tongue
OVCAR-5-Ovarian carcinoma	0.0	SCC-9-Squamous cell carcinoma of	0.0
		tongue
RL95-2-Uterine carcinoma	0.0	SCC-15-Squamous cell carcinoma	0.0
		of tongue
HelaS3-Cervical	1.4	CAL 27-Squamous cell carcinoma	0.0
adenocarcinoma		of tongue

[0667]

TABLE BO
Panel 4.1D
	Rel.	Rel.	Rel.		Rel.	Rel.	Rel.
	Exp. (%)	Exp. (%)	Exp. (%)		Exp. (%)	Exp. (%)	Exp. (%)
	Ag2362,	Ag5922,	Ag6846,		Ag2362,	Ag5922,	Ag6846,
	Run	Run	Run		Run	Run	Run
Tissue Name	169838200	247579944	279029121	Tissue Name	169838200	247579944	279029121
Secondary Th1 act	0.0	0.0	0.0	HUVEC	0.9	0.0	0.0
				IL-1beta
Secondary Th2 act	0.0	0.0	0.0	HUVEC IFN	0.0	0.0	0.0
				gamma
Secondary Tr1 act	0.0	0.0	0.0	HUVEC TNF	0.0	0.0	0.0
				alpha + IFN
				gamma
Secondary Th1 rest	0.0	0.0	0.0	HUVEC TNF	0.0	0.0	0.0
				alpha + IL4
Secondary Th2 rest	0.0	0.0	0.0	HUVEC IL-11	0.0	0.0	0.0
Secondary Tr1 rest	0.0	0.0	0.0	Lung	0.0	0.0	1.4
				Microvascular
				EC none
Primary Th1 act	0.0	0.0	0.0	Lung	0.0	0.0	0.0
				Microvascular
				EC TNF alpha +
				IL-1beta
Primary Th2 act	0.0	0.0	0.0	Microvascular	0.0	0.0	0.0
				Dermal EC none
Primary Tr1 act	0.0	0.0	0.0	Microsvasular	0.0	0.0	0.0
				Dermal EC
				TNF alpha +
				IL-1beta
Primary Th1 rest	0.0	0.0	0.0	Bronchial	0.0	0.0	0.0
				epithelium
				TNF alpha +
				IL1beta
Primary Th2 rest	0.0	0.0	0.0	Small airway	0.0	0.0	1.4
				epithelium none
Primary Tr1 rest	0.0	0.0	0.0	Small airway	0.0	0.0	0.0
				epithelium
				TNF alpha +
				IL-1beta
CD45RA CD4	3.8	0.0	4.0	Coronery artery	0.0	0.0	0.0
lymphocyte act				SMC rest
CD45RO CD4	0.0	0.0	0.0	Coronery artery	0.4	0.0	0.0
lymphocyte act				SMC TNF
				alpha + IL-1beta
CD8 lymphocyte	0.0	0.0	0.0	Astrocytes rest	8.6	0.0	4.1
act
Secondary CD8	0.0	0.0	0.0	Astrocytes	31.6	7.6	21.0
lymphocyte rest				TNF alpha +
				IL-1beta
Secondary CD8	0.0	0.0	0.0	KU-812	0.0	0.0	0.0
lymphocyte act				(Basophil) rest
CD4 lymphocyte	0.0	0.0	0.0	KU-812	0.0	0.0	0.0
none				(Basophil)
				PMA/ionomycin
2ry	0.0	0.0	0.0	CCD1106	0.0	0.0	0.0
Th1/Th2/Tr1_anti-	0.0	0.0	0.0	(Keratinocytes)	0.0	0.0	0.0
CD95 CH11				none
LAK cells rest	0.6	0.0	0.0	CCD1106	0.5	0.0	0.0
				(Keratinocytes)
				TNF alpha +
				IL-1beta
LAK cells IL-2	0.0	0.0	0.0	Liver cirrhosis	6.2	0.0	2.4
LAK cells	0.0	0.0	0.0	NCI-H292 none	0.4	0.0	0.0
IL-2 + IL-12
LAK cells	0.0	0.0	0.0	NCI-H292 IL-4	0.0	0.0	0.0
IL-2 + IFN gamma
LAK cells IL-2 +	0.0	0.0	0.0	NCI-H292 IL-9	0.0	0.0	0.0
IL-18
LAK cells	0.0	0.0	0.0	NCI-H292 IL-13	0.9	0.0	0.0
PMA/ionomycin
NK Cells IL-2 rest	0.4	0.0	0.0	NCI-H292 IFN	0.0	0.0	0.0
				gamma
Two Way MLR 3	0.0	0.0	0.0	HPAEC none	0.0	0.0	0.0
day
Two Way MLR 5	0.0	0.0	0.0	HPAEC TNF	0.0	0.0	0.0
day				alpha + IL-1beta
Two Way MLR 7	0.0	0.0	0.0	Lung fibroblast	0.0	0.0	0.0
day				none
PBMC rest	0.0	0.0	0.0	Lung fibroblast	1.2	0.0	2.4
				TNF alpha +
				IL-1beta
PBMC PWM	0.4	0.0	0.0	Lung fibroblast	0.8	0.0	0.0
				IL-4
PBMC PHA-L	0.0	0.0	0.0	Lung fibroblast	0.5	0.0	0.0
				IL-9
Ramos (B cell)	0.5	0.0	0.0	Lung fibroblast	0.6	2.8	0.0
none				IL-13
Ramos (B cell)	0.0	0.0	0.0	Lung fibroblast	0.5	0.0	0.0
ionomycin				IFN gamma
B lymphocytes	0.0	0.0	0.0	Dermal	52.1	100.0	80.7
PWM				fibroblast
				CCD1070 rest
B lymphocytes	0.0	0.0	0.0	Dermal	14.6	14.5	20.4
CD40L and IL-4				fibroblast
				CCD1070 TNF
				alpha
EOL-1 dbcAMP	0.6	0.0	0.0	Dermal	26.2	25.3	27.5
				fibroblast
				CCD1070 IL-1
				beta
EOL-1 dbcAMP	0.0	0.0	0.0	Dermal	85.3	69.3	100.0
PMA/ionomycin				fibroblast IFN
				gamma
Dendritic cells	0.0	0.0	0.0	Dermal	100.0	87.7	92.0
none				fibroblast IL-4
Dendritic cells LPS	0.0	0.0	0.0	Dermal	53.6	23.5	30.4
				Fibroblasts rest
Dendritic cells	0.4	0.0	0.0	Neutrophils	0.0	0.0	0.0
anti-CD40				TNFa + LPS
Monocytes rest	0.0	0.0	0.0	Neutrophils rest	0.1	0.0	0.0
Monocytes LPS	0.0	0.0	0.0	Colon	0.5	0.0	0.0
Macrophages rest	0.0	0.0	0.0	Lung	50.0	4.9	0.0
Macrophages LPS	0.4	0.0	0.0	Thymus	0.0	0.0	0.0
HUVEC none	0.0	0.0	0.0	Kidney	1.6	2.0	0.0
HUVEC starved	0.0	0.0	0.0

[0668]

TABLE BP
Panel 4D
	Rel.		Rel.
	xp. (%)		Exp. (%)
	Ag2362,		Ag2362,
	Run		Run
Tissue Name	164155977	Tissue Name	164155977
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	0.0
		alpha + IL-1beta
Primary Th2 act	0.0	Microvascular Dermal EC none	0.9
Primary Tr1 act	0.3	Microsvasular Dermal EC	0.0
		TNF alpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium TNF alpha +	0.0
		IL1beta
Primary Th2 rest	0.5	Small airway epithelium none	0.0
Primary Tr1 rest	0.0	Small airway epithelium TNF	0.8
		alpha + IL-1beta
CD45RA CD4 lymphocyte act	4.8	Coronery artery SMC rest	0.0
CD45RO CD4 lymphocyte act	0.1	Coronery artery SMC TNF alpha +	0.0
		IL-1beta
CD8 lymphocyte act	0.1	Astrocytes rest	11.8
Secondary CD8 lymphocyte rest	0.0	Astrocytes TNF alpha + IL-1beta	30.1
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	0.2
CH11
LAK cells rest	0.0	CCD1106 (Keratinocytes)	0.0
		TNF alpha + IL-1beta
LAK cells IL-2	0.0	Liver cirrhosis	3.3
LAK cells IL-2 + IL-12	0.0	Lupus kidney	26.4
LAK cells IL-2 + IFN gamma	0.0	NCI-H292 none	0.0
LAK cells IL-2 + IL-18	0.0	NCI-H292 IL-4	0.0
LAK cells PMA/ionomycin	0.0	NCI-H292 IL-9	0.0
NK Cells IL-2 rest	0.0	NCI-H292 IL-13	0.0
Two Way MLR 3 day	0.0	NCI-H292 IFN gamma	0.0
Two Way MLR 5 day	0.0	HPAEC none	0.0
Two Way MLR 7 day	0.0	HPAEC TNF alpha + IL-1beta	0.0
PBMC rest	0.0	Lung fibroblast none	0.4
PBMC PWM	0.0	Lung fibroblast TNF alpha + IL-1	1.7
		beta
PBMC PHA-L	0.0	Lung fibroblast IL-4	0.8
Ramos (B cell) none	0.0	Lung fibroblast IL-9	1.0
Ramos (B cell) ionomycin	0.0	Lung fibroblast IL-13	1.2
B lymphocytes PWM	1.2	Lung fibroblast IFN gamma	0.1
B lymphocytes CD40L and IL-4	0.0	Dermal fibroblast CCD1070 rest	94.6
EOL-1 dbcAMP	0.3	Dermal fibroblast CCD1070 TNF	25.2
		alpha
EOL-1 dbcAMP	0.4	Dermal fibroblast CCD1070 IL-1	21.6
PMA/ionomycin		beta
Dendritic cells none	0.0	Dermal fibroblast IFN gamma	76.3
Dendritic cells LPS	0.0	Dermal fibroblast IL-4	100.0
Dendritic cells anti-CD40	0.0	IBD Colitis 2	0.0
Monocytes rest	0.0	IBD Crohn's	1.8
Monocytes LPS	0.0	Colon	2.6
Macrophages rest	0.0	Lung	52.5
Macrophages LPS	0.0	Thymus	0.9
HUVEC none	0.0	Kidney	0.9
HUVEC starved	0.0

[0669]

TABLE BQ
Panel 5D
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag262,		Ag2362,
	Run		Run
Tissue Name	172171201	Tissue Name	172171201
97457_Patient-02go_adipose	0.3	94709_Donor 2 AM - A_adipose	17.8
97476_Patient-07sk_skeletal	8.8	94710_Donor 2 AM - B_adipose	10.6
muscle
97477_Patient-07ut_uterus	0.1	94711_Donor 2 AM - C_adipose	7.9
97478_Patient-07pl_placenta	0.1	94712_Donor 2 AD - A_adipose	52 .5
97481_Patient-08sk_skeletal	11.0	94713_Donor 2 AD - B_adipose	73.2
muscle
97482_Patient-08ut_uterus	0.7	94714_Donor 2 AD - C_adipose	61.1
97483_Patient-08pl_placenta	0.1	94742_Donor 3 U - A_Mesenchymal	3.5
		Stem Cells
97486_Patient-09sk_skeletal	2.2	94743_Donor 3 U - B_Mesenchymal	4.7
muscle		Stem Cells
97487_Patient-09ut_uterus	0.2	94730_Donor 3 AM - A_adipose	28.5
97488_Patient-09pl_placenta	0.2	94731_Donor 3 AM - B_adipose	18.9
97492_Patient-10ut_uterus	0.6	94732_Donor 3 AM - C_adipose	19.5
97493_Patient-10pl_placenta	0.1	94733_Donor 3 AD - A_adipose	100.0
97495_Patient-11go_adipose	0.0	94734_Donor 3 AD - B_adipose	69.3
97496_Patient-11sk_skeletal	0.1	94735_Donor 3 AD - C_adipose	82.4
muscle
97497_Patient-11ut_uterus	0.3	77138_Liver_HepG2untreated	2.6
97498_Patient-11pl_placenta	0.0	73556_Heart_Cardiac stromal cells	0.0
		(primary)
97500_Patient-12go_adipose	0.1	81735_Small Intestine	0.3
97501_Patient-12sk_skeletal	0.2	72409_Kidney_Proximal Convoluted	0.0
muscle		Tubule
97502_Patient-12ut_uterus	0.2	82685_Small intestine_Duodenum	0.0
97503_Patient-12pl_placenta	0.1	90650_Adrenal_Adrenocortical	0.0
		adenoma
94721_Donor 2 U -	4.7	72410_Kidney_HRCE	0.0
A_Mesenchymal Stem Cells
94722_Donor 2 U -	3.6	72411_Kidney_HRE	0.0
B_Mesenchymal Stem Cells
94723_Donor 2 U -	3.5	73139_Uterus_Uterine smooth	0.0
C_Mesenchymal Stem Cells		muscle cells

[0670] AI.05 chondrosarcoma Summary: Ag2362 Highest expression of this gene is detected in untreated chondrosarcoma cell line (SW1353) grown in complete media (CT=25.7). High expression of this gene is also detected in untreated serum starved cells. 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.

[0671] AI_comprehensive panel_v1.0 Summary: Ag2362 Highest expression of the CG105716-01 gene is detected in cartilage from osteoarthritis patient (CT=19). In addition, high expression of this gene is also seen in synovium and bone samples from the osteoarthritis patient. Furthermore, low but significant expression of this gene is also detected in synovium, bone and cartilage samples of rheumatoid arthritis patients. The CG105716-01 gene codes for cartilage oligomeric matrix protein (COMP). COMP is a noncollagenous extracellular matrix (ECM) protein which consists of five identical glycoprotein subunits, each with EGF-like and calcium-binding (thrombospondin-like) domains. COMP has been implicated in inflammatory diseases including osteochondrodysplasias and arthritis (Neidhart et al., 1997, Br J Rheumatol 36(11):1151-60, PMID: 9402858; Baitner et al, 2000, J Pediatr Orthop 20(5):594-605, PMID: 11008738; Clark et al., 1999, Arthritis Rheum November 1999;42(11):2356-64, PMID: 10555031). Therefore, therapeutic modulation of this gene product through the use of small molecule drugs, protein therapeutics or antibodies, might be beneficial in the treatment of inflammatory diseases such as rheumatoid and osteoarthritis, and osteochondrodysplasia.

[0672] General_screening_panel_v1.5 Summary: Ag2362/Ag5922/Ag5924/Ag5928/Ag5936 Multiple experiments with different probe-primer sets are in good agreement. Highest expression of this gene is detected in melanoma sample (CTs=24-30). Thus, expression of this gene can be used to distinguish this sample from other samples in this panel. In addition, significant expression of this gene is seen in colon cancer tissue, a colon cancer, lung cancer, liver cancer, and CNS cancer cell line. This gene codes for cartilage oligomeric matrix protein (COMP). Cartilage oligomeric matrix protein (COMP) is a noncollagenous extracellular matrix (ECM) protein which consists of five identical glycoprotein subunits, each with EGF-like and calcium-binding (thrombospondin-like) domains. COMP contains an RGD sequence. The RGD domain in other proteins has been shown to affect cell adhesion, migration, survival and proliferation.

[0673] Mutations of COMP can cause the osteochondrodysplasias pseudochondroplasia (PSACH) and multiple epiphyseal dysplasia (MED) (Kleerekoper et al., 2002, J Biol Chem Jan. 8, 2002; [epub ahead of print], PMID: 11782471). Based on this profile, COMP may play a role in tumor cell growth and survival based upon the cells ability to interact with the extracellular matrix. Thus, therapeutic targeting with a human monoclonal antibody might block the interaction of cancer cells, or supporting stromal elements, with extracellular matrix and thus promote cell death rather than cell survival especially in these cancers.

[0674] Additionally, this gene is expressed in two melanoma cell lines that mimic some of characteristics of activated tumor endothelial cells. Hence, antibody directed against this gene may affect endothelial growth and survival in the tumor and prevent tumor growth.

[0675] In addition, recently COMP has also been implicated in vascular calcification and fibrosis especially associated with with advanced complicated atherosclerosis (Canfield et al., 2002, J Pathol 196(2):228-34, PMID: 11793375). Therefore, therapeutic modulation of this gene could also be beneficial in the treatement of vascular calcification and fibrosis.

[0676] Among tissues with metabolic or endocrine function, this gene is expressed at high to moderate levels in pancreas, adipose, thyroid, skeletal muscle, heart, and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0677] General_screening_panel_v1.6 Summary: Ag6846 Highest expression of this gene is detected in melanoma sample (CT=26). The expression profile seen in this panel is in agreement with panel 1.5. Please see panel 1.5 for further discussion on the utility of this gene.

[0678] HASS Panel v1.0 Summary: Ag2362 The expression of this gene appears to be highest in astrocytes (Ct=28.95). There is a slight induction in expression of this gene when LnCAP cells are serum-starved and subjected to a reduced oxygen concentration and a decreased pH. These conditions resemble those typically found in tumors and suggest that in the tumors from which LnCAp cells are derived, expression of this gene may be regulated by these conditions.

[0679] Panel 1.3D Summary: Ag2362 Two experiments with same primer and probe set are in excellent agreement, with highest expression of the CG105716-01 gene in colon cancer ODO3866 sample (CTs=29). High expression of this gene are also associated with melanoma, and a liver cancer cell line. In addition, moderate expression of this gene is also seen adipose, brain, bone marrow, skeletal muscle heart, placenta, lung, testis and prostate. Please see panel 1.4 for the utility of this gene.

[0680] Panel 2D Summary: Ag2362 The expression of this gene appears to be highest in a sample derived from a breast cancer(CT=27). In addition, there appears to be substantial expression in other samples derived from breast cancer, gastric cancer, ovarian cancer, bladder cancer, thyroid cancer, kidney cancer, lung cancer, prostate cancer, liver cancer and colon cancer. Therapeutic modulation of this gene, through the use of small molecule drugs, protein therapeutics or antibodies could be of benefit in the treatment of breast, gastric, ovarian, bladder, thyroid, kidney, lung, prostate, liver or colon cancer.

[0681] Panel 3D Summary: Ag2362 Highest expression of the CG105716-01 gene is detected in cerebellum (CT=27). Low to moderate expression of this gene is associated with small cell lung cancer, lung carcinoid, and osteosarcoma. Please see panel 1.4 for the utility of this gene.

[0682] Panel 4.1D Summary: Ag2362/Ag5922/Ag6846 Multiple experiment with different probe-primer sets are in good agreement. Highest expression of this gene is detected in resting, IL-4 and IFN-gamma treated dermal fibroblasts (CTs=29-33). Expression of this gene is in agreement with panel 4D, please see panel 4D for further discussion on the utility of this gene.

[0683] Panel 4D Summary: Ag2362 Highest expression of the CG105716-01 gene is detected in IL4 treated dermal fibroblast cells (CT=29.2). High expression of this gene is seen in all the dermal fibroblast samples (CTs=29-31). Thus expression of this gene can be used to distinguish the dermal fibroblast from other samples used in this panel. Furthermore, therapeutic modulation of this gene product could be beneficial in the treatment of skin disorders, including psoriasis.

[0684] In addition, low to moderate expression of this gene is also with lung and colon. Therefore therapeutic modulation of this gene could be useful in treatment of lung and colon related diseases such as lupus and glomerulonephritis, and inflammatory bowel diseases.

[0685] Panel 5D Summary: Ag2362 Highest expression of the CG105716-01 gene is detected in a adipose sample (CT=25). In addition, high expression of this gene is seen in other adipose samples, as well as skeletal muscle. Thus, expression of this gene could be used to distinguish this sample from other samples in this panel.

[0686] C. CG153910-02: Secreted Protein CGI-100 Precursor-Like Protein.

[0687] Expression of gene CG153910-02 was assessed using the primer-probe sets Ag2642, Ag2849 and Ag2811, described in Tables CA, CB and CC. Results of the RTQ-PCR runs are shown in Tables CD, CE, CF, CG and CH.

TABLE CA
Probe Name Ag2642
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-cttctctttcggagggagtg-3′	20	491	176
Probe	TET-5′-gccacctggagtttcttcagactcca-3′-TAMRA	26	529	177
Reverse	5′-ttcctctctggactcctcgt-3′	20	571	178p

[0688]

TABLE CB
Probe Name Ag2849
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-cttctctttcggagggagtg-3′	20	491	179
Probe	TET-5′-gccacctggagtttcttcagactcca-3′-TAMRA	26	529	180
Reverse	5′-ttcctctctggactcctcgt-3′	20	571	181

[0689]

TABLE CC
Probe Name Ag2811
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-ttctctttcggagggagtg-3′	20	491	182
Probe	TET-5′-gccacctggagtttcttcagactcca-3′-TAMRA	26	529	183
Reverse	5′-ttcctctctggactcctcgt-3′	20	571	184

[0690]

TABLE CD
Panel 1.3D
	Rel.		Rel.
	Exp. ()		Exp. (%)
	Ag2642,		Ag2642,
	Run		Run
Tissue Name	167615898	Tissue Name	167615898
Liver adenocarcinoma	15.1	Kidney (fetal)	72.2
Pancreas	4.8	Renal ca. 786-0	37.9
Pancreatic ca. CAPAN 2	21.2	Renal ca. A498	24.7
Adrenal gland	7.5	Renal ca. RXF 393	35.4
Thyroid	7.3	Renal ca. ACHN	21.3
Salivary gland	3.4	Renal ca. UO-31	25.2
Pituitary gland	8.4	Renal ca. TK-10	52.1
Brain (fetal)	9.0	Liver	9.8
Brain (whole)	7.8	Liver (fetal)	12.1
Brain (amygdala)	5.8	Liver ca. (hepatoblast) HepG2	41.5
Brain (cerebellum)	13.3	Lung	6.1
Brain (hippocampus)	6.5	Lung (fetal)	10.6
Brain (substantia nigra)	11.9	Lung ca. (small cell) LX-1	21.8
Brain (thalamus)	7.2	Lung ca. (small cell) NCI-H69	13.0
Cerebral Cortex	10.1	Lung ca. (s.cell var.) SHP-77	84.7
Spinal cord	14.4	Lung ca. (large cell)NCI-H460	3.3
glio/astro U87-MG	20.9	Lung ca. (non-sm. cell) A549	42.6
glio/astro U-118-MG	40.3	Lung ca. (non-s.cell) NCI-H23	14.4
astrocytoma SW1783	50.3	Lung ca. (non-s.cell) HOP-62	15.3
neuro*; met SK-N-AS	17.3	Lung ca. (non-s.cl) NCI-H522	30.4
astrocytoma SF-539	26.1	Lung ca. (squam.) SW 900	27.9
astrocytoma SNB-75	36.3	Lung ca. (squam.) NCI-H596	20.6
glioma SNB-19	23.0	Mammary gland	6.8
glioma U251	57.0	Breast ca.* (pl.ef) MCF-7	18.8
glioma SF-295	25.9	Breast ca.* (pl.ef) MDA-MB-231	31.4
Heart (fetal)	1.9	Breast ca.* (pl.ef) T47D	52.9
Heart	7.9	Breast ca. BT-549	29.5
Skeletal muscle (fetal)	3.2	Breast ca. MDA-N	9.5
Skeletal muscle	34.6	Ovary	4.6
Bone marrow	5.5	Ovarian ca. OVCAR-3	7.1
Thymus	12.1	Ovarian ca. OVCAR-4	17.3
Spleen	7.0	Ovarian ca. OVCAR-5	100.0
Lymph node	12.1	Ovarian ca. OVCAR-8	20.2
Colorectal	10.8	Ovarian ca. IGROV-1	15.6
Stomach	4.1	Ovarian ca.* (ascites) SK-OV-3	34.4
Small intestine	3.3	Uterus	6.2
Colon ca. SW480	12.7	Placenta	1.3
Colon ca.* SW620(SW480 met)	48.3	Prostate	5.7
Colon ca. HT29	18.6	Prostate ca.* (bone met)PC-3	20.9
Colon ca. HCT-116	17.2	Testis	5.2
Colon ca. CaCo-2	33.2	Melanoma Hs688(A).T	5.4
Colon ca. tissue(ODO3866)	10.5	Melanoma* (met) Hs688(B).T	8.7
Colon ca. HCC-2998	25.0	Melanoma UACC-62	7.8
Gastric ca.* (liver met) NCI-N87	26.1	Melanoma M14	7.9
Bladder	20.7	Melanoma LOX IMVI	14.7
Trachea	3.8	Melanoma* (met) SK-MEL-5	11.7
Kidney	23.2	Adipose	32.1

[0691]

TABLE CE
Panel 2.2
	Rel.		Rel.
	Ex. (%)		Exp. (%)
	Ag2642,		Ag2642,
	Run		Run
Tissue Name	175135978	Tissue Name	175135978
Normal Colon	18.2	Kidney Margin (OD04348)	100.0
Colon cancer (OD06064)	34.2	Kidney malignant cancer	22.8
		(OD06204B)
Colon Margin (OD06064)	24.8	Kidney normal adjacent tissue	36.9
		(OD06204E)
Colon cancer (OD06159)	4.9	Kidney Cancer (OD04450-01)	53.6
Colon Margin (OD06159)	12.9	Kidney Margin (OD04450-03)	19.8
Colon cancer (OD06297-04)	4.9	Kidney Cancer 8120613	2.8
Colon Margin (OD06297-05)	20.0	Kidney Margin 8120614	11.0
CC Gr.2 ascend colon (ODO3921)	9.4	Kidney Cancer 9010320	5.8
CC Margin (ODO3921)	8.1	Kidney Margin 9010321	10.3
Colon cancer metastasis	9.7	Kidney Cancer 8120607	20.0
(OD06104)
Lung Margin (OD06104)	15.6	Kidney Margin 8120608	9.3
Colon mets to lung (OD04451-01)	26.6	Normal Uterus	19.9
Lung Margin (OD04451-02)	31.6	Uterine Cancer 064011	7.9
Normal Prostate	10.4	Normal Thyroid	4.9
Prostate Cancer (OD04410)	4.9	Thyroid Cancer 064010	8.4
Prostate Margin (OD04410)	7.9	Thyroid Cancer A302152	26.2
Normal Ovary	4.4	Thyroid Margin A302153	9.8
Ovarian cancer (OD06283-03)	12.2	Normal Breast	19.9
Ovarian Margin (OD06283-07)	10.4	Breast Cancer (OD04566)	8.5
Ovarian Cancer 064008	4.4	Breast Cancer 1024	16.6
Ovarian cancer (OD06145)	11.6	Breast Cancer (OD04590-01)	42.9
Ovarian Margin (OD06145)	13.8	Breast Cancer Mets	19.8
		(OD04590-03)
Ovarian cancer (OD06455-03)	8.4	Breast Cancer Metastasis	19.8
		(OD04655-05)
Ovarian Margin (OD06455-07)	5.6	Breast Cancer 064006	17.1
Normal Lung	16.8	Breast Cancer 9100266	5.3
Invasive poor diff. lung adeno	8.9	Breast Margin 9100265	4.5
(ODO4945-01)
Lung Margin (ODO4945-03)	13.9	Breast Cancer A209073	7.7
Lung Malignant Cancer	10.2	Breast Margin A2090734	11.0
(OD03126)
Lung Margin (OD03126)	7.5	Breast cancer (OD06083)	37.1
Lung Cancer (OD05014A)	20.2	Breast cancer node metastasis	29.5
		(OD06083)
Lung Margin (OD05014B)	19.5	Normal Liver	31.2
Lung cancer (OD06081)	8.7	Liver Cancer 1026	8.5
Lung Margin (OD06081)	14.0	Liver Cancer 1025	33.0
Lung Cancer (OD04237-01)	5.5	Liver Cancer 6004-T	25.3
Lung Margin (OD04237-02)	39.8	Liver Tissue 6004-N	7.0
Ocular Melanoma Metastasis	14.7	Liver Cancer 6005-T	21.6
Ocular Melanoma Margin (Liver)	20.9	Liver Tissue 6005-N	82.9
Melanoma Metastasis	11.4	Liver Cancer 064003	84.1
Melanoma Margin (Lung)	14.1	Normal Bladder	5.5
Normal Kidney	11.1	Bladder Cancer 1023	4.8
Kidney Ca, Nuclear grade 2	43.2	Bladder Cancer A302173	17.2
(OD04338)
Kidney Margin (OD04338)	14.5	Normal Stomach	33.7
Kidney Ca Nuclear grade 1/2	39.8	Gastric Cancer 9060397	2.4
(OD04339)
Kidney Margin (OD04339)	29.3	Stomach Margin 9060396	10.8
Kidney Ca, Clear cell type	20.3	Gastric Cancer 9060395	14.8
(OD04340)
Kidney Margin (OD04340)	26.4	Stomach Margin 9060394	21.2
Kidney Ca, Nuclear grade 3	10.4	Gastric Cancer 064005	10.8
(OD04348)

[0692]

TABLE CF
Panel 4D
	Rel.		Rel.
	Exp (%)		Exp. (%)
	Ag2642,		Ag2642,
	Run		Run
Tissue Name	165242421	Tissue Name	165242421
Secondary Th1 act	20.7	HUVEC IL-1beta	10.0
Secondary Th2 act	23.0	HUVEC IFN gamma	15.1
Secondary Tr1 act	21.6	HUVEC TNF alpha + IFN gamma	16.2
Secondary Th1 rest	6.7	HUVEC TNF alpha + IL4	14.6
Secondary Th2 rest	9.9	HUVEC IL-11	8.9
Secondary Tr1 rest	11.6	Lung Microvascular EC none	14.5
Primary Th1 act	13.2	Lung Microvascular EC TNF	16.7
		alpha + IL-1beta
Primary Th2 act	12.8	Microvascular Dermal EC none	20.7
Primary Tr1 act	15.4	Microsvasular Dermal EC	19.3
		TNF alpha + IL-1beta
Primary Th1 rest	30.8	Bronchial epithelium TNF alpha +	16.5
		IL1beta
Primary Th2 rest	17.6	Small airway epithelium none	7.2
Primary Tr1 rest	14.0	Small airway epithelium TNF	32.8
		alpha + IL-1beta
CD45RA CD4 lymphocyte act	9.9	Coronery artery SMC rest	17.3
CD45RO CD4 lymphocyte act	17.9	Coronery artery SMC TNF alpha +	11.3
		IL-1beta
CD8 lymphocyte act	9.9	Astrocytes rest	10.2
Secondary CD8 lymphocyte rest	13.4	Astrocytes TNF alpha + IL-1beta	8.1
Secondary CD8 lymphocyte act	9.2	KU-812 (Basophil) rest	13.7
CD4 lymphocyte none	6.7	KU-812 (Basophil)	50.3
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	9.5	CCD1106 (Keratinocytes) none	9.5
CH11
LAK cells rest	28.7	CCD1106 (Keratinocytes)	3.3
		TNF alpha + IL-1beta
LAK cells IL-2	22.8	Liver cirrhosis	5.5
LAK cells IL-2 + IL-12	22.1	Lupus kidney	4.4
LAK cells IL-2 + IFN gamma	27.2	NCI-H292 none	14.9
LAK cells IL-2 + IL-18	19.3	NCI-H292 IL-4	24.5
LAK cells PMA/ionomycin	27.9	NCI-H292 IL-9	12.4
NK Cells IL-2 rest	16.3	NCI-H292 IL-13	11.3
Two Way MLR 3 day	24.0	NCI-H292 IFN gamma	10.8
Two Way MLR 5 day	14.4	HPAEC none	11.2
Two Way MLR 7 day	10.7	HPAEC TNF alpha + IL-1beta	18.9
PBMC rest	9.5	Lung fibroblast none	11.2
PBMC PWM	51.1	Lung fibroblast TNF alpha + IL-1	13.7
		beta
PBMC PHA-L	20.7	Lung fibroblast IL-4	17.7
Ramos (B cell) none	25.9	Lung fibroblast IL-9	18.2
Ramos (B cell) ionomycin	100.0	Lung fibroblast IL-13	10.5
B lymphocytes PWM	53.6	Lung fibroblast IFN gamma	21.9
B lymphocytes CD40L and IL-4	23.5	Dermal fibroblast CCD1070 rest	24.3
EOL-1 dbcAMP	11.3	Dermal fibroblast CCD1070 TNF	44.8
		alpha
EOL-1 dbcAMP	15.3	Dermal fibroblast CCD1070 IL-1	20.9
PMA/ionomycin		beta
Dendritic cells none	33.0	Dermal fibroblast IFN gamma	10.2
Dendritic cells LPS	21.3	Dermal fibroblast IL-4	19.6
Dendritic cells anti-CD40	30.1	IBD Colitis 2	1.1
Monocytes rest	23.8	IBD Crohn's	1.8
Monocytes LPS	36.9	Colon	11.5
Macrophages rest	39.2	Lung	13.3
Macrophages LPS	30.1	Thymus	25.7
HUVEC none	15.3	Kidney	15.8
HUVEC starved	30.1

[0693]

TABLE CG
Panel 5 Islet
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag2849		Ag2849,
	Run		Run
Tissue Name	247609778	Tissue Name	247609778
97457_Patient-02go_adipose	24.0	94709_Donor 2 AM - A_adipose	14.7
97476_Patient-07sk_skeletal	8.8	94710_Donor 2 AM - B_adipose	9.9
muscle
97477_Patient-07ut_uterus	4.3	94711_Donor 2 AM - C_adipose	9.5
97478_Patient-07pl_placenta	14.1	94712_Donor 2 AD - A_adipose	23.8
99167_Bayer Patient 1	25.0	94713_Donor 2 AD - B_adipose	18.2
97482_Patient-08ut_uterus	7.3	94714_Donor 2 AD - C_adipose	14.8
97483_Patient-08pl_placenta	11.7	94742_Donor 3 U - A_Mesenchymal	6.9
		Stem Cells
97486_Patient-09sk_skeletal	3.4	94743_Donor 3 U - B_Mesenchymal	20.7
muscle		Stem Cells
97487_Patient-09ut_uterus	7.2	94730_Donor 3 AM - A_adipose	29.5
97488_Patient-09pl_placenta	6.8	94731_Donor 3 AM - B_adipose	12.5
97492_Patient-10ut_uterus	9.5	94732_Donor 3 AM - C_adipose	13.8
97493_Patient-10pl_placenta	22.1	94733_Donor 3 AD - A_adipose	20.3
97495_Patient-11go_adipose	15.2	94734_Donor 3 AD - B_adipose	7.9
97496_Patient-11sk_skeletal	19.1	94735_Donor 3 AD - C_adipose	38.2
muscle
97497_Patient-11ut_uterus	17.2	77138_Liver_HepG2untreated	100.00
97498_Patient-11pl_placenta	11.8	73556_Heart_Cardiac stromal cells	16.2
		(primary)
97500_Patient-12go_adipose	21.2	81735_Small Intestine	22.1
97501_Patient-12sk_skeletal	22.7	72409_Kidney_Proximal Convoluted	8.0
muscle		Tubule
97502_Patient-12ut_uterus	16.3	82685_Small intestine_Duodenum	5.1
97503_Patient-12pl_placenta	14.6	90650_Adrenal_Adrenocortical	17.3
		adenoma
94721_Donor 2 U -	11.5	72410_Kidney_HRCE	68.8
A_Mesenchymal Stem Cells
94722_Donor 2 U -	5.9	72411_Kidney_HRE	19.8
B_Mesenchymal Stem Cells
94723_Donor 2 U -	9.9	73139_Uterus_Uterine smooth	15.3
C_Mesenchymal Stem Cells		muscle cells

[0694]

TABLE CH
general_oncology_screening_panel_v_2.4
	Rel. Exp. (%)		Rel. Exp. (%)
	Ag2811, Run		Ag2811, Run
Tissue Name	264980323	Tissue Name	264980323
Colon cancer 1	24.3	Bladder NAT 2	0.4
Colon NAT 1	12.3	Bladder NAT 3	0.6
Colon cancer 2	25.7	Bladder NAT 4	4.4
Colon NAT 2	16.6	Prostate adenocarcinoma 1	27.4
Colon cancer 3	48.3	Prostate adenocarcinoma 2	4.3
Colon NAT 3	21.2	Prostate adenocarcinoma 3	20.2
Colon malignant cancer 4	57.0	Prostate adenocarcinoma 4	16.3
Colon NAT 4	11.5	Prostate NAT 5	8.7
Lung cancer 1	16.7	Prostate adenocarcinoma 6	6.8
Lung NAT 1	1.8	Prostate adenocarcinoma 7	7.7
Lung cancer 2	49.3	Prostate adenocarcinoma 8	2.3
Lung NAT 2	2.6	Prostate adenocarcinoma 9	32.5
Squamous cell carcinoma 3	29.9	Prostate NAT 10	3.8
Lung NAT 3	2.4	Kidney cancer 1	41.2
Metastatic melanoma 1	21.9	Kidney NAT 1	11.3
Melanoma 2	2.8	Kidney cancer 2	100.0
Melanoma 3	2.4	Kidney NAT 2	30.1
Metastatic melanoma 4	56.6	Kidney cancer 3	35.4
Metastatic melanoma 5	55.1	Kidney NAT 3	9.9
Bladder cancer 1	0.9	Kidney cancer 4	47.6
Bladder NAT 1	0.0	Kidney NAT 4	26.8
Bladder cancer 2	6.7

[0695] Panel 1.3D Summary: Ag2642 Highest expression of this gene is detected in ovarian cancer OVCAR-5 cell line (CT=31.8). 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, 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.

[0696] Among tissues with metabolic or endocrine function, this gene is expressed at low levels in adipose and skeletal muscle. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0697] In addition, this gene is expressed at low levels in cerebellum, substantia nigra 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.

[0698] Panel 2.2 Summary: Ag2642 Highest expression of this gene is detected in kidney sample (CT=30.8). In addition, moderate to low levels of expression of this gene is also detected in normal and cancer samples derived from colon, lung, prostate, ovary, lung, liver, kidney, thyroid, breast bladder and stomach. Therefore, therapeutic modulation of this gene or its protein product may be useful in the treatment of colon, lung, prostate, ovarian, liver, kidney, thyroid, breast, bladder and stomach cancers.

[0699] Panel 4D Summary: Ag2642 Highest expression of this gene is detected in ionomycin treated Ramos B cells (CT=28.9). This gene is expressed at low to moderate levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. 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.

[0700] Panel 5 Islet Summary: Ag2849 Highest expression of this gene is detected in liver HepG2 cell line (CT=31.3). This gene shows a widespread moderate to low expression in this panel, especially adipose, skeletal muscle, placenta, cardiac stromal cells and small intestine from diabetic and non-diabetic patients. Therefore, therapeutic modulation of this gene may be useful in the treatment of diabetic and obesity.

[0701] general oncology screening panel_v—2.4 Summary: Ag2811 Highest expression of this gene is detected in kidney cancer (CT=30.4). In addition, moderate expression of this gene is also seen in normal and cancer samples derived from colon, lung, metastatic melanoma, and prostate. Expression of this gene is consistently higher in cancer samples compared to adjacent normal tissue. Therefore, expression of this gene may be used as diagnostic marker to detect the presence of these cancers. In addition, therapeutic modulation of this gene or its protein product through the use of antibody or small molecule drug may be useful in the treatment of colon, lung, metastatic melanoma, and prostate cancers.

[0702] D. CG158564-01 and CG158564-02: Interferon Induced Transmembrane Protein-Like Protein.

[0703] Expression of gene CG158564-01 and CG158564-02 was assessed using the primer-probe set Ag5736, described in Table DA. Results of the RTQ-PCR runs are shown in Table DB. Please note that CG158564-02 represents a full-length physical clone of the CG158564-01 gene, validating the prediction of the gene sequence.

TABLE DA
Probe Name Ag5736
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-tggtcttcactggacaccat-3′	20	23	185
Probe	TET-5′-aaccttctctcctatcaacagcggc-3′-TAMRA	26	58	186
Reverse	5′-ctcctccttgagcatctcatag-3′	22	94	187

[0704]

TABLE DB
General_screening_panel_v1.5
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag5736,		Ag5736,
	Run		Run
Tissue Name	245385010	Tissue Name	245385010
Adipose	0.2	Renal ca. TK-10	0.6
Melanoma* Hs688(A).T	0.0	Bladder	100.0
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	9.3	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	14.2	Colon ca. HCT-116	0.0
Prostate Pool	0.0	Colon ca. CaCo-2	1.2
Placenta	0.0	Colon cancer tissue	0.0
Uterus Pool	0.6	Colon ca. SW1116	0.0
Ovarian ca. OVCAR-3	0.1	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	29.5	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	4.1	Stomach Pool	0.0
Ovarian ca. OVCAR-8	0.0	Bone Marrow Pool	0.0
Ovary	0.0	Fetal Heart	1.5
Breast ca. MCF-7	0.0	Heart Pool	0.0
Breast ca. MDA-MB-231	0.0	Lymph Node Pool	0.0
Breast ca. BT 549	0.0	Fetal Skeletal Muscle	0.0
Breast ca. T47D	3.1	Skeletal Muscle Pool	0.0
Breast ca. MDA-N	0.3	Spleen Pool	0.0
Breast Pool	0.0	Thymus Pool	0.0
Trachea	0.0	CNS cancer (glio/astro) U87-MG	0.6
Lung	0.0	CNS cancer (glio/astro) U-118-MG	0.1
Fetal Lung	3.6	CNS cancer (neuro; met) SK-N-AS	27.0
Lung ca. NCI-N417	1.5	CNS cancer (astro) SF-539	21.6
Lung ca. LX-1	6.1	CNS cancer (astro) SNB-75	0.0
Lung ca. NCI-H146	8.5	CNS cancer (glio) SNB-19	3.1
Lung ca. SHP-77	18.8	CNS cancer (glio) SF-295	0.0
Lung ca. A549	6.7	Brain (Amygdala) Pool	0.0
Lung ca. NCI-H526	4.0	Brain (cerebellum)	0.7
Lung ca. NCI-H23	0.9	Brain (fetal)	0.0
Lung ca. NCI-H460	0.0	Brain (Hippocampus) Pool	0.0
Lung ca. HOP-62	0.0	Cerebral Cortex Pool	0.0
Lung ca. NCI-H522	0.0	Brain (Substantia nigra) Pool	0.0
Liver	0.0	Brain (Thalamus) Pool	0.0
Fetal Liver	0.0	Brain (whole)	0.0
Liver ca. HepG2	9.3	Spinal Cord Pool	0.0
Kidney Pool	0.0	Adrenal Gland	0.0
Fetal Kidney	0.7	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	41.2	Pancreatic ca. CAPAN2	0.0
Renal ca. UO-31	0.0	Pancreas Pool	0.0

[0705] General_screening_panel_v1.5 Summary: Ag5736 Highest expression of this gene is detected in bladder (CT=27). Therefore, expression of this gene may be used to distinguish bladder from other samples used in this panel.

[0706] In addition, low expression of this gene is also detected in number of cancer cell lines derived from melanoma, renal, liver, lung, breast, ovarian, colon, and prostate cancer. Therefore, expression of this gene may be used as diagnostic marker to detect presence of these cancers and therapeutic modulation of this gene may be useful in the treatment of these cancers.

[0707] E. CG159093-01, CG159093-02 and CG159093-03: Type Ib Membrane Protein-Like Protein.

[0708] Expression of gene CG159093-01, CG159093-02 and CG159093-03 was assessed using the primer-probe sets Ag5738, Ag6690 and Ag6714, described in Tables EA, EB and EC. Results of the RTQ-PCR runs are shown in Tables ED, EE and EF. Please note that probe-primer set Ag5738 is specific for CG159093-01.

TABLE EA
Probe Name Ag5738
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-tcgagtaaagcagcttgtcttc-3′	22	692	188
Probe	TET-5′-acccaaagactttcccatcgtctcct-3′-TAMRA	26	721	189
Reverse	5′-cttctccttcatgtttctggaa-3′	22	755	190

[0709]

TABLE EB
Probe Name Ag6690
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-acccttttcattccgatcaa-3′	20	497	191
Probe	TET-5′-tgtcaccagatacaggttttctctcg-3′-TAMRA	26	523	192
Reverse	5′-tccttttaccgtctccagagttt-3′	22	550	193

[0710]

TABLE EC
Probe Name Ag6714
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-acccttttcattccgatcaa-3′	20	497	194
Probe	TET-5′-tgtcaccagatacaggttttctctcg-3′-TAMRA	26	523	195
Reverse	5′-ctcctttaccgtctccagagtt-3′	22	551	196

[0711]

TABLE ED
CNS_neurodegeneration_v1.0
	Rel.	Rel.		Rel.	Rel.
	Exp. (%)	Exp. (%)		Exp. (%)	Exp. (%)
	Ag6690,	Ag6714,		Ag6690,	Ag6714,
	Run	Run		Run	Run
Tissue Name	276247142	276596842	issue Name	276247142	276596842
AD 1 Hippo	17.4	13.5	Control (Path) 3	8.8	6.2
			Temporal Ctx
AD 2 Hippo	15.1	14.6	Control (Path) 4	32.8	35.1
			Temporal Ctx
AD 3 Hippo	18.2	8.3	AD 1 Occipital Ctx	61.1	46.0
AD 4 Hippo	7.0	5.7	AD 2 Occipital Ctx	0.0	0.0
			(Missing)
AD 5 Hippo	100.0	100.0	AD 3 Occipital Ctx	19.3	17.3
AD 6 Hippo	62.9	58.2	AD 4 Occipital Ctx	24.8	17.6
Control 2 Hippo	18.7	19.5	AD 5 Occipital Ctx	21.2	36.9
Control 4 Hippo	9.2	8.7	AD 6 Occipital Ctx	26.1	24.0
Control (Path) 3	6.5	3.0	Control 1 Occipital	3.1	4.5
Hippo			Ctx
AD 1 Temporal Ctx	37.1	32.3	Control 2 Occipital	49.0	47.0
			Ctx
AD 2 Temporal Ctx	28.3	31.4	Control 3 Occipital	44.8	33.9
			Ctx
AD 3 Temporal Ctx	21.9	17.6	Control 4 Occipital	8.7	5.8
			Ctx
AD 4 Temporal Ctx	31.9	22.4	Control (Path) 1	82.9	65.5
			Occipital Ctx
AD 5 Inf Temporal	51.4	58.6	Control (Path) 2	31.4	11.2
Ctx			Occipital Ctx
AD 5 Sup Temporal	25.2	25.7	Control (Path) 3	2.6	3.3
Ctx			Occipital Ctx
Ad 6 Inf Temporal	22.5	70.7	Control (Path) 4	24.5	25.2
Ctx			Occipital Ctx
AD 6 Sup Temporal	82.9	79.6	Control 1 Parietal	14.2	10.0
Ctx			Ctx
Control 1 Temporal	6.4	10.0	Control 2 Parietal	51.1	44.4
Ctx			Ctx
Control 2 Temporal	22.8	18.7	Control 3 Parietal	24.1	12.2
Ctx			Ctx
Control 3 Temporal	27.7	27.5	Control (Path) 1	42.3	54.7
Ctx			Parietal Ctx
Control 3 Temporal	10.7	10.2	Control (Path) 2	31.9	29.7
Ctx			Parietal Ctx
Control (Path) 1	41.8	39.8	Control (Path) 3	5.6	6.3
Temporal Ctx			Parietal Ctx
Control (Path) 2	62.9	62.0	Control (Path) 4	35.8	29.9
Temporal Ctx			Parietal Ctx

[0712]

TABLE EE
General screening_panel_v1.6
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag6690,		Ag6690,
	Run		Run
Tissue Name	277259300	Tissue Name	277259300
Adipose	2.9	Renal ca. TK-10	8.9
Melanoma* Hs688(A).T	2.2	Bladder	11.3
Melanoma* Hs688(B).T	2.1	Gastric ca. (liver met.) NCI-N87	100.0
Melanoma* M14	0.6	Gastric ca. KATO III	6.6
Melanoma* LOXIMVI	0.5	Colon ca. SW-948	4.0
Melanoma* SK-MEL-5	0.5	Colon ca. SW480	0.0
Squamous cell carcinoma SCC-4	1.1	Colon ca.* (SW480 met) SW620	5.0
Testis Pool	0.9	Colon ca. HT29	3.1
Prostate ca.* (bone met) PC-3	5.8	Colon ca. HCT-116	7.1
Prostate Pool	0.9	Colon ca. CaCo-2	6.7
Placenta	1.1	Colon cancer tissue	16.5
Uterus Pool	0.2	Colon ca. SW1116	0.5
Ovarian ca. OVCAR-3	1.9	Colon ca. Colo-205	9.6
Ovarian ca. SK-OV-3	4.7	Colon ca. SW-48	12.1
Ovarian ca. OVCAR-4	0.5	Colon Pool	3.0
Ovarian ca. OVCAR-5	28.3	Small Intestine Pool	1.5
Ovarian ca. IGROV-1	1.9	Stomach Pool	2.4
Ovarian ca. OVCAR-8	0.8	Bone Marrow Pool	0.1
Ovary	2.2	Fetal Heart	1.9
Breast ca. MCF-7	1.2	Heart Pool	0.8
Breast ca. MDA-MB-231	0.3	Lymph Node Pool	2.9
Breast ca. BT 549	6.0	Fetal Skeletal Muscle	1.0
Breast ca. T47D	2.5	Skeletal Muscle Pool	0.5
Breast ca. MDA-N	0.1	Spleen Pool	3.7
Breast Pool	2.6	Thymus Pool	14.8
Trachea	3.6	CNS cancer (glio/astro)	0.7
		U87-MG
Lung	0.4	CNS cancer (glio/astro)	3.4
		U-118-MG
Fetal Lung	8.2	CNS cancer (neuro; met)	2.6
		SK-N-AS
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-539	1.8
Lung ca. LX-1	7.8	CNS cancer (astro) SNB-75	5.0
Lung ca. NCI-H146	0.3	CNS cancer (glio) SNB-19	2.9
Lung ca. SHP-77	0.6	CNS cancer (glio) SF-295	20.9
Lung ca. A549	4.0	Brain (Amygdala) Pool	0.7
Lung ca. NCI-H526	0.1	Brain (cerebellum)	8.1
Lung ca. NCI-H23	7.1	Brain (fetal)	5.3
Lung ca. NCI-H460	1.4	Brain (Hippocampus) Pool	0.7
Lung ca. HOP-62	2.8	Cerebral Cortex Pool	1.6
Lung ca. NCI-H522	4.2	Brain (Substantia nigra) Pool	1.2
Liver	0.4	Brain (Thalamus) Pool	1.5
Fetal Liver	5.0	Brain (whole)	2.2
Liver ca. HepG2	2.5	Spinal Cord Pool	1.4
Kidney Pool	2.8	Adrenal Gland	0.4
Fetal Kidney	2.9	Pituitary gland Pool	0.3
Renal ca. 786-0	1.9	Salivary Gland	0.7
Renal ca. A498	8.6	Thyroid (female)	0.3
Renal ca. ACHN	2.0	Pancreatic ca. CAPAN2	10.7
Renal ca. UO-31	2.1	Pancreas Pool	7.3

[0713]

TABLE EF
Panel 4.1D
	Rel.		Rel.
	Exp. ()		Exp. (%)
	Ag6690,		Ag6690,
	Run		Run
Tissue Name	276043961	Tissue Name	276043961
Secondary Th1 act	57.0	HUVEC IL-1beta	6.8
Secondary Th2 act	75.8	HUVEC IFN gamma	7.4
Secondary Tr1 act	29.9	HUVEC TNF alpha + IFN gamma	1.5
Secondary Th1 rest	24.3	HUVEC TNF alpha + IL4	0.8
Secondary Th2 rest	28.9	HUVEC IL-11	3.9
Secondary Tr1 rest	12.9	Lung Microvascular EC none	23.0
Primary Th1 act	6.4	Lung Microvascular EC TNF	5.9
		alpha + IL-1beta
Primary Th2 act	39.0	Microvascular Dermal EC none	0.6
Primary Tr1 act	28.9	Microsvasular Dermal EC	2.1
		TNF alpha + IL-1beta
Primary Th1 rest	5.5	Bronchial epithelium TNF alpha +	15.1
		IL1beta
Primary Th2 rest	9.0	Small airway epithelium none	3.3
Primary Tr1 rest	10.7	Small airway epithelium TNF	12.8
		alpha + IL-1beta
CD45RA CD4 lymphocyte act	22.8	Coronery artery SMC rest	5.6
CD45RO CD4 lymphocyte act	65.1	Coronery artery SMC TNF alpha +	8.8
		IL-1beta
CD8 lymphocyte act	23.0	Astrocytes rest	7.1
Secondary CD8 lymphocyte	9.6	Astrocytes TNF alpha + IL-1beta	7.0
rest
Secondary CD8 lymphocyte	16.0	KU-812 (Basophil) rest	4.0
act
CD4 lymphocyte none	15.6	KU-812 (Basophil)	2.8
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	19.5	CCD1106 (Keratinocytes) none	10.2
CH11
LAK cells rest	11.0	CCD1106 (Keratinocytes)	18.0
		TNF alpha + IL-1beta
LAK cells IL-2	40.9	Liver cirrhosis	27.2
LAK cells IL-2 + IL-12	4.2	NCI-H292 none	7.7
LAK cells IL-2 + IFN gamma	28.1	NCI-H292 IL-4	6.2
LAK cells IL-2 + IL-18	12.8	NCI-H292 IL-9	10.7
LAK cells PMA/ionomycin	4.3	NCI-H292 IL-13	6.4
NK Cells IL-2 rest	92.7	NCI-H292 IFN gamma	9.5
Two Way MLR 3 day	58.6	HPAEC none	3.4
Two Way MLR 5 day	4.9	HPAEC TNF alpha + IL-1beta	2.5
Two Way MLR 7 day	21.0	Lung fibroblast none	15.7
PBMC rest	1.4	Lung fibroblast TNF alpha + IL-1	8.1
		beta
PBMC PWM	15.1	Lung fibroblast IL-4	2.8
PBMC PHA-L	23.7	Lung fibroblast IL-9	6.3
Ramos (B cell) none	1.5	Lung fibroblast IL-13	3.2
Ramos (B cell) ionomycin	7.3	Lung fibroblast IFN gamma	6.0
B lymphocytes PWM	13.4	Dermal fibroblast CCD1070 rest	8.1
B lymphocytes CD40L and	100.0	Dermal fibroblast CCD1070 TNF	94.6
IL-4		alpha
EOL-1 dbcAMP	8.7	Dermal fibroblast CCD1070 IL-1	5.7
		beta
EOL-1 dbcAMP	5.8	Dermal fibroblast IFN gamma	1.7
PMA/ionomycin
Dendritic cells none	6.7	Dermal fibroblast IL-4	5.4
Dendritic cells LPS	2.9	Dermal Fibroblasts rest	2.3
Dendritic cells anti-CD40	1.2	Neutrophils TNF a + LPS	1.6
Monocytes rest	0.5	Neutrophils rest	17.2
Monocytes LPS	8.0	Colon	21.5
Macrophages rest	2.3	Lung	0.0
Macrophages LPS	0.0	Thymus	54.7
HUVEC none	1.4	Kidney	6.9
HUVEC starved	6.6

[0714] CNS_neurodegeneration_v1.0 Summary: Ag6690/Ag6714 Two experiments with same probe-primer sets are in good 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 1.6 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.

[0715] General_screening_panel_v1.6 Summary: Ag6690 Highest expression of this gene is detected in a gastric cancer NCI-N87 cell line (CT=27.4). High to moderate expression of this gene is also seen in cancer cell lines derived from melanoma, pancreatic, brain, colon, renal, lung ovarian, breast, and prostate cancers. Therefore, therapeutic modulation of this gene may be useful in the treatment of these cancers.

[0716] Among tissues with metabolic or endocrine function, this gene is expressed at moderate levels in pancreas, adipose, fetal 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.

[0717] Interestingly, this gene is expressed at much higher levels in fetal (CTs=31) when compared to adult lung and liver (CTs=35). This observation suggests that expression of this gene can be used to distinguish fetal from adult lung and liver, respectively. In addition, the relative overexpression of this gene in fetal tissue suggests that the protein product may enhance lung and 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 lung and liver related diseases.

[0718] In addition, this gene is expressed at low levels in all regions of the central nervous system examined, including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, therapeutic modulation of this gene product may be useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0719] Panel 4.1D Summary: Ag6690 Highest expression of this gene is detected in CD40L and IL-4 treated B lymphocytes (CT=31.9). In addition, moderate to low level of expression of this gene is also detected in thymus, TNF alpha activated dermal fibroblast, IL-2 treated resting NK cells, 2 way MLR, lung fibroblast, liver cirrhosis, activated keratinocytes, activated LAK cells, activated bronchial and small airway epithelium, lung microvascular endothelial cells, activated primary and secondary polarized T cells, naive and memory T cells, PWM treated B cells, and activated lymphocytes. Therefore, therapeutic modulation of this gene product may reduce or eliminate the symptoms in patients with several types of autoimmune and inflammatory diseases, such as lupus erythematosus, Crohn's disease, ulcerative colitis, multiple sclerosis, chronic obstructive pulmonary disease, asthma, emphysema, rheumatoid arthritis, or psoriasis.

[0720] F. CG159390-01: Thrombospondin Type 1 Domain Containing Protein-Like Protein.

[0721] Expression of gene CG159390-01 was assessed using the primer-probe set Ag5800, described in Table FA. Results of the RTQ-PCR runs are shown in Table FB.

TABLE FA
Probe Name Ag5800
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-ctggaacgtgaccctgatc-3′	20	857	197
Probe	TET-5′-agacacatccgcgtggaacacag-3′-TAMRA	23	889	198
Reverse	5′-ccccatcagtgatcctagga-3′	20	932	199

[0722]

TABLE FB
General screening_panel_v1.5
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag5800,		Ag5800,
	Run		Run
Tissue Name	246267831	Tissue Name	246267831
Adipose	0.0	Renal ca. TK-10	1.4
Melanoma* Hs688(A).T	16.4	Bladder	1.1
Melanoma* Hs688(B).T	41.2	Gastric ca. (liver met.) NCI-N87	1.1
Melanoma* M14	0.0	Gastric ca. KATO III	27.2
Melanoma* LOXIMVI	0.0	Colon ca. SW-948	2.7
Melanoma* SK-MEL-5	30.8	Colon ca. SW480	8.8
Squamous cell carcinoma SCC-4	12.8	Colon ca.* (SW480 met) SW620	19.5
Testis Pool	0.0	Colon ca. HT29	0.0
Prostate ca.* (bone met) PC-3	0.0	Colon ca. HCT-116	11.3
Prostate Pool	0.0	Colon ca. CaCo-2	35.6
Placenta	0.0	Colon cancer tissue	6.3
Uterus Pool	9.5	Colon ca. SW1116	0.8
Ovarian ca. OVCAR-3	6.1	Colon ca. Colo-205	3.7
Ovarian ca. SK-OV-3	14.4	Colon ca. SW-48	7.2
Ovarian ca. OVCAR-4	0.0	Colon Pool	1.0
Ovarian ca. OVCAR-5	39.5	Small Intestine Pool	1.1
Ovarian ca. IGROV-1	0.0	Stomach Pool	0.0
Ovarian ca. OVCAR-8	100.0	Bone Marrow Pool	4.3
Ovary	0.0	Fetal Heart	28.3
Breast ca. MCF-7	0.0	Heart Pool	0.8
Breast ca. MDA-MB-231	54.0	Lymph Node Pool	6.2
Breast ca. BT 549	0.0	Fetal Skeletal Muscle	3.8
Breast ca. T47D	2.3	Skeletal Muscle Pool	0.0
Breast ca. MDA-N	0.8	Spleen Pool	0.8
Breast Pool	0.0	Thymus Pool	0.0
Trachea	0.0	CNS cancer (glio/astro)	0.0
		U87-MG
Lung	0.0	CNS cancer (glio/astro)	65.1
		U-118-MG
Fetal Lung	0.0	CNS cancer (neuro; met)	0.0
		SK-N-AS
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-539	4.1
Lung ca. LX-1	49.7	CNS cancer (astro) SNB-75	10.2
Lung ca. NCI-H146	0.0	CNS cancer (glio) SNB-19	0.0
Lung ca. SHP-77	0.0	CNS cancer (glio) SF-295	4.7
Lung ca. A549	0.0	Brain (Amygdala) Pool	0.9
Lung ca. NCI-H526	0.0	Brain (cerebellum)	5.3
Lung ca. NCI-H23	0.0	Brain (fetal)	0.0
Lung ca. NCI-H460	0.0	Brain (Hippocampus) Pool	0.0
Lung ca. HOP-62	12.3	Cerebral Cortex Pool	0.0
Lung ca. NCI-H522	23.5	Brain (Substantia nigra) Pool	0.0
Liver	0.0	Brain (Thalamus) Pool	0.7
Fetal Liver	0.0	Brain (whole)	2.7
Liver ca. HepG2	0.0	Spinal Cord Pool	0.7
Kidney Pool	20.7	Adrenal Gland	0.0
Fetal Kidney	0.0	Pituitary gland Pool	1.1
Renal ca. 786-0	2.2	Salivary Gland	0.0
Renal ca. A498	2.7	Thyroid (female)	1.0
Renal ca. ACHN	11.2	Pancreatic ca. CAPAN2	0.0
Renal ca. UO-31	7.6	Pancreas Pool	0.0

[0723] General_screening_panel_v1.5 Summary: Ag5800 Highest expression of this gene is detected in a ovarian cancer OVCAR-8 cell line (CT=32). Moderate to low levels of expression of this gene is also seen in ovarian cancer OVCAR-5 cell line, melanoma Hs688(B).T and SK-MEL-5 cell lines, Breast cancer MDA-MB-231 cell line, lung cancer LX-1 cell line, gastric cancer KATO III cell line, colon cancer CaCo-2 cell line, and brain cancer U-118-MG cell lines. Therefore, expression of this gene may be used as diagnostic marker to detect the presence of melanoma, ovarian, breast, lun, gastric, colon and brain cancers. In addition, therapeutic modulation of this gene or its protein product through the use of antibodies or small molecule drug may be useful in the treatment of these cancers.

[0724] Low expression of this gene is also seen in fetal heart. Interestingly, this gene is expressed at much higher levels in fetal (CT=34.6) when compared to adult heart (CT=39.7). This observation suggests that expression of this gene can be used to distinguish fetal from adult heart. In addition, the relative overexpression of this gene in fetal tissue suggests that the protein product may enhance heart 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 heart related diseases.

[0725] G. CG159498-01: ST71 Membrane Protein-Like Protein.

[0726] Expression of gene CG159498-01 was assessed using the primer-probe sets Ag5546 and Ag8056, described in Tables GA and GB. Results of the RTQ-PCR runs are shown in Tables GC, GD and GE.

TABLE GA
Probe Name Ag5546
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-tctctgatctgcctgtgctaac-3′	22	1700	200
Probe	TET-5′-caacaaatatcttccattgtccagctgg-3′-TAMRA	28	1722	201
Reverse	5′-tttgatgtatttatggcagcaa-3′	122	1778	202

[0727]

TABLE GB
Probe Name Ag8056
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-cctttgaggctgtgtgagaa-3′	120	190	203
Probe	TET-5′-aaaatacagtcaccgctgccaaa-3′-TAMRA	23	210	204
Reverse	5′-ggtccctgtaagtgccacata-3′	21	256	205

[0728]

TABLE GC
CNS_neurodegeneration_v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag5546,		Ag5546,
	Run		Run
Tissue Name	247121694	Tissue Name	247121694
AD 1 Hippo	11.3	Control (Path) 3 Temporal Ctx	8.1
AD 2 Hippo	9.5	Control (Path) 4 Temporal Ctx	26.4
AD 3 Hippo	1.8	AD 1 Occipital Ctx	14.8
AD 4 Hippo	6.0	AD 2 Occipital Ctx (Missing)	0.0
AD 5 Hippo	62.4	AD 3 Occipital Ctx	5.1
AD 6 Hippo	39.5	AD 4 Occipital Ctx	14.1
Control 2 Hippo	11.9	AD 5 Occipital Ctx	16.0
Control 4 Hippo	6.1	AD 6 Occipital Ctx	20.7
Control (Path) 3 Hippo	1.2	Control 1 Occipital Ctx	0.3
AD 1 Temporal Ctx	6.4	Control 2 Occipital Ctx	50.3
AD 2 Temporal Ctx	0.0	Control 3 Occipital Ctx	17.8
AD 3 Temporal Ctx	7.6	Control 4 Occipital Ctx	6.0
AD 4 Temporal Ctx	14.3	Control (Path) 1 Occipital Ctx	87.7
AD 5 Inf Temporal Ctx	100.0	Control (Path) 2 Occipital Ctx	6.3
AD 5 SupTemporal Ctx	33.7	Control (Path) 3 Occipital Ctx	4.6
AD 6 Inf Temporal Ctx	62.0	Control (Path) 4 Occipital Ctx	5.5
AD 6 Sup Temporal Ctx	50.0	Control 1 Parietal Ctx	7.3
Control 1 Temporal Ctx	4.6	Control 2 Parietal Ctx	25 .2
Control 2 Temporal Ctx	41.2	Control 3 Parietal Ctx	16.0
Control 3 Temporal Ctx	2.1	Control (Path) 1 Parietal Ctx	53.2
Control 4 Temporal Ctx	5.4	Control (Path) 2 Parietal Ctx	14.6
Control (Path) 1 Temporal Ctx	66.9	Control (Path) 3 Parietal Ctx	4.3
Control (Path) 2 Temporal Ctx	22.5	Control (Path) 4 Parietal Ctx	23.0

[0729]

TABLE GD
General screening_panel_vl.7
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag5546,		Ag5546,
	Run		Run
Tissue Name	318350003	Tissue Name	318350003
Adipose	23.5	Gastric ca. (liver met.) NCI-N87	0.5
HUVEC	5.4	Stomach	0.2
Melanoma* Hs688(A).T	0.0	Colon ca. SW-948	1.3
Melanoma* Hs688(B).T	9.8	Colon ca. SW480	0.3
Melanoma (met) SK-MEL-5	2.5	Colon ca. (SW480 met) SW620	23.5
Testis	8.4	Colon ca. HT29	13.8
Prostate ca. (bone met) PC-3	0.3	Colon Ca. HCT-116	26.4
Prostate ca. DU145	4.5	Colon cancer tissue	0.2
Prostate pool	2.4	Colon ca. SW1116	1.4
Uterus pool	1.8	Colon ca. Colo-205	2.3
Ovarian ca. OVCAR-3	2.4	Colon ca. SW-48	1.7
Ovarian ca. (ascites) SK-OV-3	1.7	Colon	8.7
Ovarian ca. OVCAR-4	6.0	Small Intestine	3.5
Ovarian ca. OVCAR-5	13.5	Fetal Heart	7.4
Ovarian ca. IGROV-1	9.2	Heart	1.4
Ovarian ca. OVCAR-8	24.8	Lymph Node pool 1	2.7
Ovary	13.3	Lymph Node pool 2	25.5
Breast ca. MCF-7	3.0	Fetal Skeletal Muscle	4.3
Breast ca. MDA-MB-231	38.2	Skeletal Muscle pool	0.8
Breast ca. BT-549	2.5	Skeletal Muscle	10.4
Breast ca. T47D	3.2	Spleen	8.4
Breast pool	7.2	Thymus	4.6
Trachea	28.7	CNS cancer (glio/astro) SF-268	2.8
Lung	30.6	CNS cancer (glio/astro) T98G	12.8
Fetal Lung	21.2	CNS cancer (neuro; met)	1.0
		SK-N-AS
Lung ca. NCI-N417	2.8	CNS cancer (astro) SF-539	18.4
Lung ca. LX-1	2.9	CNS cancer (astro) SNB-75	13.9
Lung ca. NCI-H146	6.9	CNS cancer (glio) SNB-19	12.2
Lung ca. SHP-77	39.2	CNS cancer (glio) SF-295	2.9
Lung ca. NCI-H23	22.8	Brain (Amygdala)	7.2
Lung ca. NCI-H460	6.7	Brain (Cerebellum)	33.9
Lung ca. HOP-62	14.7	Brain (Fetal)	18.0
Lung ca. NCI-H522	21.9	Brain (Hippocampus)	5.7
Lung ca. DMS-114	2.9	Cerebral Cortex pool	6.2
Liver	0.1	Brain (Substantia nigra)	2.3
Fetal Liver	0.6	Brain (Thalamus)	9.6
Kidney pool	19.3	Brain (Whole)	100.0
Fetal Kidney	3.3	Spinal Cord	2.1
Renal ca. 786-0	13.6	Adrenal Gland	10.3
Renal ca. A498	0.7	Pituitary Gland	4.6
Renal ca. ACHN	5.0	Salivary Gland	1.9
Renal ca. UO-31	4.0	Thyroid	24.1
Renal ca. TK-10	9.8	Pancreatic ca. PANC-1	2.4
Bladder	12.4	Pancreas pool	1.4

[0730]

TABLE GE
Panel 4.1D
	Rel.		Rel.
	Ep. (%)		Exp. (%)
	Ag5546,		Ag5546,
	Run		Run
Tissue Name	246950177	Tissue Name	246950177
Secondary Th1 act	7.4	HUVEC IL-1beta	15.3
Secondary Th2 act	47.3	HUVEC IFN gamma	39.0
Secondary Tr1 act	11.4	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	3.2
Secondary Tr1 rest	0.0	Lung Microvascular EC none	51.4
Primary Th1 act	2.8	Lung Microvascular EC TNF	7.2
		alpha + IL-1beta
Primary Th2 act	8.6	Microvascular Dermal EC none	0.0
Primary Tr1 act	7.5	Microsvasular Dermal EC	3.8
		TNF alpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium TNF alpha +	12.2
		IL1beta
Primary Th2 rest	0.0	Small airway epithelium none	9.5
Primary Tr1 rest	1.1	Small airway epithelium TNF	31.0
		alpha + IL-1beta
CD45RA CD4 lymphocyte act	16.3	Coronery artery SMC rest	12.2
CD45RO CD4 lymphocyte act	20.2	Coronery artery SMC TNF alpha +	4.5
		IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	4.5
Secondary CD8 lymphocyte	8.2	Astrocytes TNF alpha + IL-1beta	0.0
rest
Secondary CD8 lymphocyte	0.0	KU-812 (Basophil) rest	11.1
act
CD4 lymphocyte none	1.5	KU-812 (Basophil)	28.3
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	2.7	CCD1106 (Keratinocytes) none	13.2
CH11
LAK cells rest	8.1	CCD1106 (Keratinocytes)	10.5
		TNF alpha + IL-1beta
LAK cells IL-2	0.7	Liver cirrhosis	3.0
LAK cells IL-2 + IL-12	3.8	NCI-H292 none	3.6
LAK cells IL-2 + IFN gamma	4.4	NCI-H292 IL-4	13.4
LAK cells IL-2 + IL-18	3.3	NCI-H292 IL-9	19.8
LAK cells PMA/ionomycin	16.0	NCI-H292 IL-13	30.4
NK Cells IL-2 rest	55.1	NCI-H292 IFN gamma	18.9
Two Way MLR 3 day	1.1	HPAEC none	8.0
Two Way MLR 5 day	0.5	HPAEC TNF alpha + IL-1beta	45.1
Two Way MLR 7 day	3.2	Lung fibroblast none	17.6
PBMC rest	0.0	Lung fibroblast TNF alpha + IL-1	12.9
		beta
PBMC PWM	3.3	Lung fibroblast IL-4	21. 8
PBMC PHA-L	6.0	Lung fibroblast IL-9	15.3
Ramos (B cell) none	0.0	Lung fibroblast IL-13	1.2
Ramos (B cell) ionomycin	7.2	Lung fibroblast IFN gamma	61.6
B lymphocytes PWM	9.1	Dermal fibroblast CCD1070 rest	44.1
B lymphocytes CD40L and	12.7	Dermal fibroblast CCD1070 TNF	100.0
IL-4		alpha
EOL-1 dbcAMP	21.6	Dermal fibroblast CCD1070 IL-1	17.2
		beta
EOL-1 dbcAMP	3.3	Dermal fibroblast IFN gamma	8.2
PMA/ionomycin
Dendritic cells none	18.2	Dermal fibroblast IL-4	25.7
Dendritic cells LPS	4.7	Dermal Fibroblasts rest	13.0
Dendritic cells anti-CD40	0.0	Neutrophils TNF a + LPS	1.6
Monocytes rest	1.2	Neutrophils rest	1.7
Monocytes LPS	28.5	Colon	0.9
Macrophages rest	1.9	Lung	1.4
Macrophages LPS	6.2	Thymus	5.8
HUVEC none	18.7	Kidney	26.6
HUVEC starved	21.6

[0731] CNS_neurodegeneration_v1.0 Summary: Ag5546 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 1.7 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.

[0732] General_screening_panel_v1.7 Summary: Ag5546 Highest expression of this gene is detected in whole brain (CT=26.4). 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.

[0733] 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, 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.

[0734] Among tissues with metabolic or endocrine function, this gene is expressed at moderate to low levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, 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.

[0735] Interestingly, this gene is expressed at much higher levels in fetal (CT=33.8) when compared to adult liver (CT=36.9). 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.

[0736] Panel 4.1D Summary: Ag5546 Highest expression of this gene is detected in TNF alpha activated dermal fibroblast (CT=31.4). Moderate to low expression of this gene is detected in activated primary and secondary Th2 cells, activated memory and naive T cells, resting IL-2 treated NK cells, resting eosinophils and dendritic cells, activated mononcytes, HUVEC, lung microvascular endothelial cells, bronchial and small airway epithelial cells, basophils and keratinocytes, activated mucoepidermoid NCI-H292 cells, activated HPAEC, resting and activated lung and dermal fibroblasts, and kidney. 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.

[0737] H. CG160152-03: MS4A7-Like Protein.

[0738] Expression of gene CG160152-03 was assessed using the primer-probe set Ag6881, described in Table HA. Results of the RTQ-PCR runs are shown in Table HB.

TABLE HA
Probe Name Ag6881
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-gttcttggggacctgagca-3′	19	146	206
Probe	TET-5′-tgcagtaacagaactcactgcatttgaggtcaa-3′-TAMRA	33	167	207
Reverse	5′-gctgtcagcaaggaggaagag-3′	21	209	208

[0739]

TABLE HB
General screening_panel_v1.6
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag6881,		Ag6881,
	Run		Run
Tissue Name	278388060	Tissue Name	278388060
Adipose	30.1	Renal ca. TK-10	0.0
Melanoma* Hs688(A).T	0.0	Bladder	100.0
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	4.3	Colon ca. HT29	0.0
Prostate ca.* (bone met) PC-3	0.0	Colon ca. HCT-116	0.0
Prostate Pool	9.0	Colon ca. CaCo-2	0.0
Placenta	5.9	Colon cancer tissue	83.5
Uterus Pool	1.4	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	24.5
Ovarian ca. OVCAR-5	0.0	Small Intestine Pool	6.0
Ovarian ca. IGROV-1	0.0	Stomach Pool	9.6
Ovarian ca. OVCAR-8	0.0	Bone Marrow Pool	9.2
Ovary	17.8	Fetal Heart	5.5
Breast ca. MCF-7	0.0	Heart Pool	5.8
Breast ca. MDA-MB-231	0.0	Lymph Node Pool	14.5
Breast ca. BT 549	0.0	Fetal Skeletal Muscle	5.3
Breast ca. T47D	0.0	Skeletal Muscle Pool	1.6
Breast ca. MDA-N	1.2	Spleen Pool	78.5
Breast Pool	23.7	Thymus Pool	23.7
Trachea	11.5	CNS cancer (glio/astro)	0.0
		U87-MG
Lung	4.5	CNS cancer (glio/astro)	0.0
		U-118-MG
Fetal Lung	25.2	CNS cancer (neuro; met)	0.0
		SK-N-AS
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-539	0.0
Lung ca. LX-1	0.0	CNS cancer (astro) SNB-75	0.0
Lung ca. NCI-H146	0.0	CNS cancer (glio) SNB-19	0.0
Lung ca. SHP-77	0.0	CNS cancer (glio) SF-295	0.0
Lung ca. A549	0.0	Brain (Amygdala) Pool	2.9
Lung ca. NCI-H526	0.0	Brain (cerebellum)	5.3
Lung ca. NCI-H23	0.0	Brain (fetal)	0.6
Lung ca. NCI-H460	0.0	Brain (Hippocampus) Pool	9.0
Lung ca. HOP-62	0.0	Cerebral Cortex Pool	5.4
Lung ca. NCI-H522	0.0	Brain (Substantia nigra) Pool	2.5
Liver	7.2	Brain (Thalamus) Pool	4.5
Fetal Liver	33.9	Brain (whole)	6.9
Liver ca. HepG2	0.0	Spinal Cord Pool	7.1
Kidney Pool	19.1	Adrenal Gland	16.2
Fetal Kidney	3.0	Pituitary gland Pool	0.4
Renal ca. 786-0	0.0	Salivary Gland	1.9
Renal ca. A498	0.0	Thyroid (female)	7.6
Renal ca. ACHN	0.0	Pancreatic ca. CAPAN2	0.0
Renal ca. UO-31	0.0	Pancreas Pool	8.1

[0740] General_screening_panel_v1.6 Summary: Ag6881 Highest expression of this gene is detected mainly in bladder. Therefore, expression of this gene may be used to distinguish bladder from other samples in this panel and also, therapeutic modulation of this gene may be useful in the treatment of bladder related diseases.

[0741] In addition, moderate to low levels of expression of this gene is also seen in spleen, thymus, colon, lymph node, kidney, ovary, breast, fetal lung and fetal liver. Therefore, therapeutic modulation of this gene may be useful in the treatment of diseases that affect these tissues.

[0742] Moderate expression of this gene is also detected in colon cancer tissue sample. Therefore, expression of this gene may be used as diagnostic marker to detect the presence of colon cancer. Furthermore, therapeutic modulation of this gene or its protein product may be useful in the treatment of colon cancer.

[0743] I. CG160185-01: Membrane Protein-Like Protein.

[0744] Expression of gene CG160185-01 was assessed using the primer-probe set Ag7844, described in Table IA. Results of the RTQ-PCR runs are shown in Tables IB and IC.

TABLE IA
Probe Name Ag7844
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-tccctcctgtcacccttatc-3′	20	530	209
Probe	TET-5′-ctttacgtctgccccaggctccattt-3′-TAMRA	26	563	210
Reverse	5′-aggaaagtcagggtggtttg-3′	20	608	211

[0745]

TABLE IB
AI_comprehensive panel_v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag7844,		Ag7844,
	Run		Run
Tissue Name	317419925	Tissue Name	317419925
110967 COPD-F	1.8	112427 Match Control Psoriasis-F	34.2
110980 COPD-F	2.4	112418 Psoriasis-M	3.1
110968 COPD-M	6.0	112723 Match Control Psoriasis-M	14.1
110977 COPD-M	27.7	112419 Psoriasis-M	5.6
110989 Emphysema-F	18.2	112424 Match Control Psoriasis-M	6.6
110992 Emphysema-F	4.9	112420 Psoriasis-M	22.7
110993 Emphysema-F	0.0	112425 Match Control Psoriasis-M	4.0
110994 Emphysema-F	2.0	104689 (MF) OA Bone-Backus	3.6
110995 Emphysema-F	9.2	104690 (MF) Adj “Normal”	4.2
		Bone-Backus
110996 Emphysema-F	2.0	104691 (MF) OA Synovium-	5.7
		Backus
110997 Asthma-M	0.5	104692 (BA) OA Cartilage-Backus	0.0
111001 Asthma-F	3.1	104694 (BA) OA Bone-Backus	0.4
111002 Asthma-F	5.3	104695 (BA) Adj “Normal”	1.5
		Bone-Backus
111003 Atopic Asthma-F	12.2	104696 (BA) OA Synovium-	2.8
		Backus
111004 Atopic Asthma-F	6.1	104700 (SS) OA Bone-Backus	1.5
111005 Atopic Asthma-F	6.4	104701 (SS) Adj “Normal”	1.9
		Bone-Backus
111006 Atopic Asthma-F	1.8	104702 (SS) OA Synovium-	1.4
		Backus
111417 Allergy-M	1.5	117093 OA Cartilage Rep7	10.2
112347 Allergy-M	0.2	112672 OA Bone5	2.0
112349 Normal Lung-F	0.1	112673 OA Synovium5	2.8
112357 Normal Lung-F	60.3	112674 OA Synovial Fluid cells5	1.7
112354 Normal Lung-M	32.1	117100 OA Cartilage Rep14	3.6
112374 Crohns-F	28.3	112756 OA Bone9	100.0
112389 Match Control Crohns-F	1.9	112757 OA Synovium9	2.0
112375 Crohns-F	16.6	112758 OA Synovial Fluid Cells9	3.8
112732 Match Control Crohns-F	0.9	117125 RA Cartilage Rep2	6.8
112725 Crohns-M	3.4	113492 Bone2 RA	1.7
112387 Match Control	1.4	113493 Synovium2 RA	1.8
Crohns-M
112378 Crohns-M	0.4	113494 Syn Fluid Cells RA	3.2
112390 Match Control	39.0	113499 Cartilage4 RA	1.5
Crohns-M
112726 Crohns-M	2.9	113500 Bone4 RA	2.7
112731 Match Control	3.3	113501 Synovium4 RA	2.9
Crohns-M
112380 Ulcer Col-F	6.9	113502 Syn Fluid Cells4 RA	1.3
112734 Match Control Ulcer	3.7	113495 Cartilage3 RA	2.9
Col-F
112384 Ulcer Col-F	18.8	113496 Bone3 RA	2.8
112737 Match Control Ulcer	2.5	113497 Synovium3 RA	2.3
Col-F
112386 Ulcer Col-F	3.0	113498 Syn Fluid Cells3 RA	5.1
112738 Match Control Ulcer	1.5	117106 Normal Cartilage Rep20	4.0
Col-F
112381 Ulcer Col-M	0.0	113663 Bone3 Normal	0.0
112735 Match Control Ulcer	1.7	113664 Synovium3 Normal	0.0
Col-M
112382 Ulcer Col-M	3.0	113665 Syn Fluid Cells3 Normal	0.2
112394 Match Control Ulcer	2.6	117107 Normal Cartilage Rep22	1.7
Col-M
112383 Ulcer Col-M	19.8	113667 Bone4 Normal	5.4
112736 Match Control Ulcer	1.1	113668 Synovium4 Normal	8.2
Col-M
112423 Psoriasis-F	3.7	113669 Syn Fluid Cells4 Normal	7.1

[0746]

TABLE IC
General screening_panel_v1.7
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag7844,		Ag7844,
	Run		Run
Tissue Name	318010060	Tissue Name	318010060
Adipose	0.2	Gastric ca. (liver met.) NCI-N87	0.0
HUVEC	0.0	Stomach	0.0
Melanoma* Hs688(A).T	0.0	Colon ca. SW-948	0.2
Melanoma* Hs688(B).T	0.7	Colon ca. SW480	0.0
Melanoma (met) SK-MEL-5	1.3	Colon ca. (SW480 met) SW620	9.9
Testis	0.4	Colon ca. HT29	0.0
Prostate ca. (bone met) PC-3	0.0	Colon ca. HCT-116	2.7
Prostate ca. DU145	2.4	Colon cancer tissue	0.0
Prostate pool	0.1	Colon ca. SW1116	0.0
Uterus pool	0.0	Colon ca. Colo-205	0.0
Ovarian ca. OVCAR-3	0.0	Colon ca. SW-48	0.0
Ovarian ca. (ascites) SK-OV-3	0.0	Colon	0.1
Ovarian ca. OVCAR-4	1.0	Small Intestine	0.1
Ovarian ca. OVCAR-5	0.8	Fetal Heart	0.0
Ovarian ca. IGROV-1	1.2	Heart	0.0
Ovarian ca. OVCAR-8	0.1	Lymph Node pool 1	0.0
Ovary	0.2	Lymph Node pool 2	0.1
Breast ca. MCF-7	0.2	Fetal Skeletal Muscle	0.0
Breast ca. MDA-MB-231	0.0	Skeletal Muscle pool	0.0
Breast ca. BT-549	0.3	Skeletal Muscle	0.0
Breast ca. T47D	0.3	Spleen	0.0
Breast pool	0.1	Thymus	0.0
Trachea	0.7	CNS cancer (glio/astro) SF-268	0.0
Lung	0.1	CNS cancer (glio/astro) T98G	0.1
Fetal Lung	0.1	CNS cancer (neuro; met)	0.0
		SK-N-AS
Lung ca. NCI-N417	3.7	CNS cancer (astro) SF-539	0.2
Lung ca. LX-1	0.1	CNS cancer (astro) SNB-75	0.2
Lung ca. NCI-H146	11.0	CNS cancer (glio) SNB-19	0.0
Lung ca. SHP-77	8.7	CNS cancer (glio) SF-295	0.2
Lung ca. NCI-H23	1.9	Brain (Amygdala)	8.7
Lung ca. NCI-H460	0.1	Brain (Cerebellum)	68.3
Lung ca. HOP-62	0.6	Brain (Fetal)	100.0
Lung ca. NCI-H522	16.5	Brain (Hippocampus)	6.3
Lung ca. DMS-114	1.7	Cerebral Cortex pool	6.4
Liver	0.0	Brain (Substantia nigra)	3.5
Fetal Liver	0.0	Brain (Thalamus)	11.8
Kidney pool	0.0	Brain (Whole)	62.0
Fetal Kidney	0.0	Spinal Cord	1.3
Renal ca. 786-0	0.1	Adrenal Gland	1.3
Renal ca. A498	1.4	Pituitary Gland	2.9
Renal ca. ACHN	0.1	Salivary Gland	0.7
Renal ca. UO-31	0.0	Thyroid	0.2
Renal ca. TK-10	0.6	Pancreatic ca. PANC-1	1.3
Bladder	0.0	Pancreas pool	0.0

[0747] AI_comprehensive panel_v1.0 Summary: Ag7844 Highest expression of this gene is detected in orthoarthritis (OA) bone (CT=29). In addition, low levels of expression of this gene is also seen in samples derived from normal and OA/rheumatoid arthritis bone and adjacent bone, cartilage, synovium and synovial fluid samples, from normal lung, COPD lung, emphysema, atopic asthma, Crohn's disease (normal matched control and diseased), ulcerative colitis(normal matched control and diseased), and psoriasis (normal matched control and diseased). Therefore, therapeutic modulation of this gene product may ameliorate symptoms/conditions associated with autoimmune and inflammatory disorders including psoriasis, allergy, asthma, inflammatory bowel disease, rheumatoid arthritis and osteoarthritis

[0748] General_screening_panel_v1.7 Summary: Ag7844 Highest expression of this gene is detected in fetal brain (CT=23.7). High expression of this gene is seen mainly in all the brain region 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.

[0749] Low expression of this gene is also seen in number of cancer cell lines derived from pancreatic, 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, colon, lung, liver, renal, breast, ovarian, prostate, melanoma and brain cancers.

[0750] Among tissues with metabolic or endocrine function, this gene is expressed at moderate levels in adipose, adrenal gland, thyroid, pituitary gland, 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.

[0751] J. CG160244-01: Type IIIa Membrane Protein-Like Protein.

[0752] Expression of gene CG160244-01 was assessed using the primer-probe set Ag7845, described in Table JA. Results of the RTQ-PCR runs are shown in Tables JB, JC and JD.

TABLE JA
Probe Name Ag7845
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-agtgtggccttgagcagtg-3′	19	3983	212
Probe	TET-5′-cccatccagcatccacgtttccagc-3′-TAMRA	24	4003	213
Reverse	5′-ggtcagggcaggcagt-3′	16	4042	214

[0753]

TABLE JB
CNS_neurodegeneration_v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag7845,		Ag7845,
	Run		Run
Tissue Name	319510461	Tissue Name	319510461
AD 1 Hippo	23.0	Control (Path) 3 Temporal Ctx	7.4
AD 2 Hippo	35.1	Control (Path) 4 Temporal Ctx	46.0
AD 3 Hippo	14.0	AD 1 Occipital Ctx	25.0
AD 4 Hippo	18.4	AD 2 Occipital Ctx (Missing)	0.0
AD 5 hippo	100.0	AD 3 Occipital Ctx	9.9
AD 6 Hippo	62.9	AD 4 Occipital Ctx	43.2
Control 2 Hippo	32.1	AD 5 Occipital Ctx	23.0
Control 4 Hippo	20.0	AD 6 Occipital Ctx	46.7
Control (Path) 3 Hippo	7.7	Control 1 Occipital Ctx	6.2
AD 1 Temporal Ctx	37.1	Control 2 Occipital Ctx	66.0
AD 2 Temporal Ctx	38.4	Control 3 Occipital Ctx	31.6
AD 3 Temporal Ctx	15.7	Control 4 Occipital Ctx	10.5
AD 4 Temporal Ctx	44.4	Control (Path) 1 Occipital Ctx	99.3
AD 5 Inf Temporal Ctx	97.3	Control (Path) 2 Occipital Ctx	18.0
AD 5 SupTemporal Ctx	62.0	Control (Path) 3 Occipital Ctx	6.9
AD 6 Inf Temporal Ctx	59.9	Control (Path) 4 Occipital Ctx	24.1
AD 6 Sup Temporal Ctx	61.6	Control 1 Parietal Ctx	14.3
Control 1 Temporal Ctx	10.2	Control 2 Parietal Ctx	76.8
Control 2 Temporal Ctx	31.6	Control 3 Parietal Ctx	26.4
Control 3 Temporal Ctx	33.0	Control (Path) 1 Parietal Ctx	70.2
Control 4 Temporal Ctx	22.2	Control (Path) 2 Parietal Ctx	31.2
Control (Path) 1 Temporal Ctx	66.4	Control (Path) 3 Parietal Ctx	6.7
Control (Path) 2 Temporal Ctx	44.8	Control (Path) 4 Parietal Ctx	45.7

[0754]

TABLE JC
General_screening_panel_v1.7
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag7845,		Ag7845,
	Run		Run
Tissue Name	318010062	Tissue Name	318010062
Adipose	64.6	Gastric ca. (liver met.) NCI-N87	3.0
HUVEC	45.7	Stomach	3.9
Melanoma* Hs688(A).T	0.0	Colon ca. SW-948	12.6
Melanoma* Hs688(B).T	23.0	Colon ca. SW480	2.2
Melanoma (met) SK-MEL-5	24.7	Colon ca. (SW480 met) SW620	32.1
Testis	27.7	Colon ca. HT29	24.3
Prostate ca. (bone met) PC-3	0.9	Colon ca. HCT-116	23.8
Prostate ca. DU145	28.9	Colon cancer tissue	2.9
Prostate pool	26.1	Colon ca. SW1116	11.7
Uterus pool	5.1	Colon ca. Colo-205	4.9
Ovarian ca. OVCAR-3	6.9	Colon ca. SW-48	4.1
Ovarian ca. (ascites) SK-OV-3	3.2	Colon	23.0
Ovarian ca. OVCAR-4	35.1	Small Intestine	6.7
Ovarian ca. OVCAR-5	12.7	Fetal Heart	9.3
Ovarian ca. IGROV-1	42.9	Heart	9.0
Ovarian ca. OVCAR-8	40.1	Lymph Node pool 1	15.6
Ovary	30.4	Lymph Node pool 2	52.1
Breast ca. MCF-7	17.0	Fetal Skeletal Muscle	12.2
Breast ca. MDA-MB-231	43.2	Skeletal Muscle pool	4.7
Breast ca. BT-549	59.9	Skeletal Muscle	20.2
Breast ca. T47D	46.3	Spleen	17.7
Breast pool	21.8	Thymus	23.3
Trachea	48.6	CNS cancer (glio/astro) SF-268	8.0
Lung	52.9	CNS cancer (glio/astro) T98G	12.7
Fetal Lung	71.2	CNS cancer (neuro; met)	9.0
		SK-N-AS
Lung ca. NCI-N417	5.4	CNS cancer (astro) SF-539	39.5
Lung ca. LX-1	4.9	CNS cancer (astro) SNB-75	20.7
Lung ca. NCI-H146	17.3	CNS cancer (glio) SNB-19	21.9
Lung ca. SHP-77	21.3	CNS cancer (glio) SF-295	7.7
Lung ca. NCI-H23	25.7	Brain (Amygdala)	15.2
Lung ca. NCI-H460	15.5	Brain (Cerebellum)	46.7
Lung ca. HOP-62	63.7	Brain (Fetal)	82.9
Lung ca. NCI-H522	20.3	Brain (Hippocampus)	15.2
Lung ca. DMS-114	13.9	Cerebral Cortex pool	14.0
Liver	14.8	Brain (Substantia nigra)	6.8
Fetal Liver	30.1	Brain (Thalamus)	18.3
Kidney pool	73.2	Brain (Whole)	100.0
Fetal Kidney	27.2	Spinal Cord	8.5
Renal ca. 786-0	40.9	Adrenal Gland	57.8
Renal ca. A498	49.0	Pituitary Gland	34.9
Renal ca. ACHN	30.6	Salivary Gland	24.0
Renal ca. UO-31	39.0	Thyroid	59.9
Renal ca. TK-10	30.1	Pancreatic ca. PANC-1	18.3
Bladder	39.2	Pancreas pool	7.5

[0755]

TABLE JD
Panel 4.1D
	Rel.		Rel.
	Exp. ()		Exp. (%)
	Ag7845,		Ag7845,
	Run		Run
Tissue Name	313916921	Tissue Name	313916921
Secondary Th1 act	55.5	HUVEC IL-1beta	44.8
Secondary Th2 act	82.9	HUVEC IFN gamma	55.1
Secondary Tr1 act	28.5	HUVEC TNF alpha + IFN gamma	13.5
Secondary Th1 rest	4.8	HUVEC TNF alpha + IL4	20.2
Secondary Th2 rest	10.4	HUVEC IL-11	42.9
Secondary Tr1 rest	10.9	Lung Microvascular EC none	70.7
Primary Th1 act	6.9	Lung Microvascular EC TNF	27.9
		alpha + IL-1beta
Primary Th2 act	34.6	Microvascular Dermal EC none	10.2
Primary Tr1 act	24.8	Microsvasular Dermal EC	15.9
		TNF alpha + IL-1beta
Primary Th1 rest	1.9	Bronchial epithelium TNF alpha +	14.6
		IL1beta
Primary Th2 rest	5.5	Small airway epithelium none	21.5
Primary Tr1 rest	1.7	Small airway epithelium TNF	42.3
		alpha + IL-1beta
CD45RA CD4 lymphocyte act	27.2	Coronery artery SMC rest	35.6
CD45RO CD4 lymphocyte act	46.0	Coronery artery SMC TNF	31.6
		alpha + IL-1beta
CD8 lymphocyte act	7.5	Astrocytes rest	20.7
Secondary CD8 lymphocyte	7.1	Astrocytes TNF alpha + IL-1beta	11.6
rest
Secondary CD8 lymphocyte	4.8	KU-812 (Basophil) rest	14.2
act
CD4 lymphocyte none	6.4	KU-812 (Basophil)	16.6
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	19.3	CCD1106 (Keratinocytes) none	25.3
CH11
LAK cells rest	19.5	CCD1106 (Keratinocytes)	11.0
		TNF alpha + IL-1beta
LAK cells IL-2	9.2	Liver cirrhosis	18.3
LAK cells IL-2 + IL-12	1.9	NCI-H292 none	28.5
LAK cells IL-2 + IFN gamma	6.0	NCI-H292 IL-4	33.2
LAK cells IL-2 + IL-18	4.7	NCI-H292 IL-9	34.9
LAK cells PMA/ionomycin	40.1	NCI-H292 IL-13	41.5
NK Cells IL-2 rest	62.0	NCI-H292 IFN gamma	12.9
Two Way MLR 3 day	28.9	HPAEC none	19.2
Two Way MLR 5 day	3.9	HPAEC TNF alpha + IL-1beta	77.4
Two Way MLR 7 day	9.6	Lung fibroblast none	61.1
PBMC rest	4.2	Lung fibroblast TNF alpha +	52.5
		IL-1beta
PBMC PWM	11.7	Lung fibroblast IL-4	21.0
PBMC PHA-L	8.5	Lung fibroblast IL-9	20.6
Ramos (B cell) none	0.7	Lung fibroblast IL-13	13.5
Ramos (B cell) ionomycin	8.2	Lung fibroblast IFN gamma	51.4
B lymphocytes PWM	7.7	Dermal fibroblast CCD1070 rest	40.1
B lymphocytes CD40L and	40.9	Dermal fibroblast CCD1070 TNF	95.3
IL-4		alpha
EOL-1 dbcAMP	20.9	Dermal fibroblast CCD1070	38.4
		IL-1beta
EOL-1 dbcAMP	5.4	Dermal fibroblast IFN gamma	27.0
PMA/ionomycin
Dendritic cells none	18.2	Dermal fibroblast IL-4	40.1
Dendritic cells LPS	10.0	Dermal Fibroblasts rest	42.6
Dendritic cells anti-CD40	11.4	Neutrophils TNF a + LPS	14.6
Monocytes rest	21.8	Neutrophils rest	87.7
Monocytes LPS	100.0	Colon	9.0
Macrophages rest	11.4	Lung	2.0
Macrophages LPS	13.1	Thymus	17.4
HUVEC none	18.2	Kidney	52.1
HUVEC starved	35.6

[0756] CNS_neurodegeneration_v1.0 Summary: Ag7845 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 1.7 for a discussion of the potential utility of this gene in treatment of central nervous system disorders.

[0757] General_screening_panel_v1.7 Summary: Ag7845 Highest expression of this gene is seen in a sample derived from the whole brain (CT=23.8). This gene is also expressed at high levels in all regions of the CNS examined on this panel, 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.

[0758] This gene is widely expressed in this panel, with high levels of expression seen in brain, colon, gastric, lung, breast, ovarian, and melanoma cancer cell lines. This expression profile suggests a role for this gene product in cell survival and proliferation. Modulation of this gene product may be useful in the treatment of cancer.

[0759] 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.

[0760] Panel 4.1D Summary: Ag7845 Highest expression of this gene is seen in LPS treated monocytes (CT=29.2). This gene is also expressed at moderate levels in a wide range of cell types of significance in the immune response in health and disease. These cells include members of the T-cell, B-cell, endothelial cell, macrophage/monocyte, and peripheral blood mononuclear cell family, as well as epithelial and fibroblast cell types from lung and skin, and normal tissues represented by colon, lung, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.7 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.

[0761] K. CG162177-02: Folate Receptor Beta-Like Protein.

[0762] Expression of gene CG162177-02 was assessed using the primer-probe set Ag5905, described in Table KA. Results of the RTQ-PCR runs are shown in Tables KB and KC.

TABLE KA
Probe Name Ag5905
			Start	Seq ID
Primers		Length	Position	No
Forward	5′40 -acctcccgcctgtacaac-3′	18	304	215
Probe	TET-5′-atcttgccgcagtggtcccagttaaa-3′-TAMRA	26	322	216
Reverse	5′-catagagacaggtgtcctggat-3′	22	373	217

[0763]

TABLE KB
AI_comprehensive panel_v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag5905,		Ag5905,
	Run		Run
Tissue Name	247682891	Tissue Name	247682891
110967 COPD-F	5.7	112427 Match Control Psoriasis-F	9.6
110980 COPD-F	5.9	112418 Psoriasis-M	10.2
110968 COPD-M	6.9	112723 Match Control Psoriasis-M	2.0
110977 COPD-M	9.9	112419 Psoriasis-M	9.5
110989 Emphysema-F	3.4	112424 Match Control Psoriasis-M	2.6
110992 Emphysema-F	5.8	112420 Psoriasis-M	10.9
110993 Emphysema-F	2.0	112425 Match Control Psoriasis-M	6.4
110994 Emphysema-F	2.0	104689 (MF) OA Bone-Backus	31.6
110995 Emphysema-F	5.8	104690 (MF) Adj “Normal”	13.3
		Bone-Backus
110996 Emphysema-F	4.0	104691 (MF) OA Synovium-	100.0
		Backus
110997 Asthma-M	4.4	104692 (BA) OA Cartilage-Backus	2.3
111001 Asthma-F	6.7	104694 (BA) OA Bone-Backus	37.6
111002 Asthma-F	4.6	104695 (BA) Adj “Normal”	26.6
		Bone-Backus
111003 Atopic Asthma-F	4.4	104696 (BA) OA Synovium-	90.1
		Backus
111004 Atopic Asthma-F	4.4	104700 (SS) OA Bone-Backus	12.8
111005 Atopic Asthma-F	4.5	104701 (SS) Adj “Normal”	33.0
		Bone-Backus
111006 Atopic Asthma-F	1.0	104702 (SS) OA Synovium-	79.0
		Backus
111417 Allergy-M	2.7	117093 OA Cartilage Rep7	2.1
112347 Allergy-M	0.0	112672 OA Bone5	9.7
112349 Normal Lung-F	0.0	112673 OA Synovium5	4.0
112357 Normal Lung-F	2.9	112674 OA Synovial Fluid cells5	3.7
112354 Normal Lung-M	1.6	117100 OA Cartilage Rep14	2.6
112374 Crohns-F	4.9	112756 OA Bone9	2.9
112389 Match Control Crohns-F	5.1	112757 OA Synovium9	1.4
112375 Crohns-F	2.8	112758 OA Synovial Fluid Cells9	8.8
112732 Match Control Crohns-F	2.8	117125 RA Cartilage Rep2	16.7
112725 Crohns-M	1.0	113492 Bone2 RA	5.6
112387 Match Control	1.8	113493 Synovium2 RA	2.6
Crohns-M
112378 Crohns-M	0.1	113494 Syn Fluid Cells RA	3.0
112390 Match Control	1.5	113499 Cartilage4 RA	2.4
Crohns-M
112726 Crohns-M	1.8	113500 Bone4 RA	2.7
112731 Match Control	4.5	113501 Synovium4 RA	2.3
Crohns-M
112380 Ulcer Col-F	0.7	113502 Syn Fluid Cells4 RA	1.4
112734 Match Control Ulcer	12.3	113495 Cartilage3 RA	4.4
Col-F
112384 Ulcer Col-F	2.7	113496 Bone3 RA	5.1
112737 Match Control Ulcer	0.6	113497 Synovium3 RA	2.2
Col-F
112386 Ulcer Col-F	1.1	113498 Syn Fluid Cells3 RA	6.4
112738 Match Control Ulcer	2.3	117106 Normal Cartilage Rep20	3.1
Col-F
112381 Ulcer Col-M	0.7	113663 Bone3 Normal	1.9
112735 Match Control Ulcer	8.8	113664 Synovium3 Normal	0.0
Col-M
112382 Ulcer Col-M	5.1	113665 Syn Fluid Cells3 Normal	0.0
112394 Match Control Ulcer	1.4	117107 Normal Cartilage Rep22	2.6
Col-M
112383 Ulcer Col-M	3.2	113667 Bone4 Normal	1.0
112736 Match Control Ulcer	5.1	113668 Synovium4 Normal	2.0
Col-M
112423 Psoriasis-F	4.0	113669 Syn Fluid Cells4 Normal	3.5

[0764]

TABLE KC
General_screening_panel_v1.5
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag5905,		Ag5905,
	Run		Run
Tissue Name	247453527	Tissue Name	247453527
Adipose	62.4	Renal ca. TK-10	0.0
Melanoma* Hs688(A).T	0.0	Bladder	40.6
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	11.1	Colon ca. HT29	0.0
Prostate ca.* (bone met) PC-3	0.0	Colon ca. HCT-116	0.0
Prostate Pool	9.8	Colon ca. CaCo-2	0.0
Placenta	62.0	Colon cancer tissue	37.6
Uterus Pool	4.9	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	35.8
Ovarian ca. OVCAR-5	0.0	Small Intestine Pool	12.2
Ovarian ca. IGROV-1	0.0	Stomach Pool	17.1
Ovarian ca. OVCAR-8	0.0	Bone Marrow Pool	17.6
Ovary	31.0	Fetal Heart	4.3
Breast ca. MCF-7	0.0	Heart Pool	18.8
Breast ca. MDA-MB-231	0.0	Lymph Node Pool	19.3
Breast ca. BT 549	0.0	Fetal Skeletal Muscle	18.9
Breast ca. T47D	0.0	Skeletal Muscle Pool	13.7
Breast ca. MDA-N	0.0	Spleen Pool	4.3
Breast Pool	24.5	Thymus Pool	16.7
Trachea	6.0	CNS cancer (glio/astro)	0.0
		U87-MG
Lung	4.4	CNS cancer (glio/astro)	0.0
		U-118-MG
Fetal Lung	24.0	CNS cancer (neuro; met)	0.0
		SK-N-AS
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-539	0.0
Lung ca. LX-1	0.0	CNS cancer (astro) SNB-75	0.0
Lung ca. NCI-H146	0.5	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	3.5
Lung ca. NCI-H526	0.0	Brain (cerebellum)	9.0
Lung ca. NCI-H23	0.0	Brain (fetal)	6.3
Lung ca. NCI-H460	0.0	Brain (Hippocampus) Pool	6.6
Lung ca. HOP-62	0.0	Cerebral Cortex Pool	6.7
Lung ca. NCI-H522	0.0	Brain (Substantia nigra) Pool	8.8
Liver	12.4	Brain (Thalamus) Pool	6.2
Fetal Liver	45.4	Brain (whole)	20.6
Liver ca. HepG2	0.0	Spinal Cord Pool	12.0
Kidney Pool	42.6	Adrenal Gland	33.2
Fetal Kidney	10.4	Pituitary gland Pool	5.8
Renal ca. 786-0	0.0	Salivary Gland	3.8
Renal ca. A498	100.0	Thyroid (female)	3.4
Renal ca. ACHN	0.0	Pancreatic ca. CAPAN2	0.0
Renal ca. UO-31	0.0	Pancreas Pool	31.4

[0765] AI_comprehensive panel_v1.0 Summary: Ag5905 Highest expression is seen in a sample of OA synovium (CT=26.7). In addition, this gene is expressed at high to moderate levels in a cluster of samples derived from OA. Thus, expression of this gene could be used to differentiate between the OA derived samples and other samples on this panel and as a marker of OA. Furthermore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of OA.

[0766] General_screening_panel_v1.5 Summary: Ag5905 Highest expression is seen in a renal cancer cell line (CT=31.9), with low levels seen in a sample derived from a colon cancer. Thus, expression of this gene may be used to differentiate between the renal cell line and other samples on this panel.

[0767] Low levels of expression are also seen in whole brain, spinal cord, pancreas, adrenal, fetal and adult skeletal muscle, heart, liver and fetal liver, and adipose. This suggests that this gene product may be involved in diseases that involve these organs.

[0768] Panel 4.1D Summary: Ag5905 Expression of this gene is limited to the lung and liver cirrhosis.

[0769] L. CG162443-01: Advanced Glycosylation End Product-Specific Receptor Precursor-Like Protein.

[0770] Expression of gene CG162443-01 was assessed using the primer-probe set Ag6685, described in Table LA. Results of the RTQ-PCR runs are shown in Tables LB and LC. Please note that CG162443-02 represents a full-length physical clone of the CG162443-01 gene, validating the prediction of the gene sequence.

TABLE LA
Probe Name Ag6685
			Start	Seq ID
Primers		Length	Position	No
Forward	5′-cagcatcagcatcatcgaa-3′	19	930	218
Probe	TET-5′-ctcccacagagcctgcagttggc-3′-TAMRA	23	963	219
Reverse	5′-tagagttcccagccctgatc-3′	20	986	220

[0771]

TABLE LB
General_screening_panel_v1.6
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag6685,		Ag6685,
	Run		Run
Tissue Name	277259221	Tissue Name	277259221
Adipose	0.2	Renal ca. TK-10	0.9
Melanoma* Hs688(A).T	0.5	Bladder	1.1
Melanoma* Hs688(B).T	0.4	Gastric ca. (liver met.) NCI-N87	0.4
Melanoma* M14	1.1	Gastric ca. KATO III	1.0
Melanoma* LOXIMVI	0.7	Colon ca. SW-948	0.9
Melanoma* SK-MEL-5	0.0	Colon ca. SW480	0.8
Squamous cell carcinoma SCC-4	0.0	Colon ca.* (SW480 met) SW620	0.8
Testis Pool	0.3	Colon ca. HT29	0.5
Prostate ca.* (bone met) PC-3	0.1	Colon ca. HCT-116	0.4
Prostate Pool	1.2	Colon ca. CaCo-2	0.7
Placenta	0.4	Colon cancer tissue	0.3
Uterus Pool	1.4	Colon ca. SW1116	0.4
Ovarian ca. OVCAR-3	1.1	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	1.3	Colon Ca. SW-48	0.5
Ovarian ca. OVCAR-4	0.0	Colon Pool	1.5
Ovarian ca. OVCAR-5	2.7	Small Intestine Pool	1.6
Ovarian ca. IGROV-1	1.8	Stomach Pool	1.3
Ovarian ca. OVCAR-8	3.1	Bone Marrow Pool	0.8
Ovary	0.2	Fetal Heart	1.9
Breast ca. MCF-7	2.3	Heart Pool	0.8
Breast ca. MDA-MB-231	0.5	Lymph Node Pool	2.2
Breast ca. BT 549	4.2	Fetal Skeletal Muscle	0.8
Breast ca. T47D	0.9	Skeletal Muscle Pool	0.6
Breast ca. MDA-N	0.2	Spleen Pool	1.7
Breast Pool	1.5	Thymus Pool	6.4
Trachea	0.3	CNS cancer (glio/astro)	0.1
		U87-MG
Lung	0.4	CNS cancer (glio/astro)	2.6
		U-118-MG
Fetal Lung	100.0	CNS cancer (neuro; met)	1.4
		SK-N-AS
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-539	0.4
Lung ca. LX-1	0.6	CNS cancer (astro) SNB-75	1.0
Lung ca. NCI-H146	0.0	CNS cancer (glio) SNB-19	3.6
Lung ca. SHP-77	0.3	CNS cancer (glio) SF-295	2.8
Lung ca. A549	0.6	Brain (Amygdala) Pool	0.6
Lung ca. NCI-H526	0.0	Brain (cerebellum)	0.9
Lung ca. NCI-H23	0.9	Brain (fetal)	0.6
Lung ca. NCI-H460	0.2	Brain (Hippocampus) Pool	0.8
Lung ca. HOP-62	0.8	Cerebral Cortex Pool	0.4
Lung ca. NCI-H522	0.8	Brain (Substantia nigra) Pool	0.0
Liver	0.0	Brain (Thalamus) Pool	1.3
Fetal Liver	0.5	Brain (whole)	0.8
Liver ca. HepG2	1.7	Spinal Cord Pool	0.6
Kidney Pool	4.6	Adrenal Gland	0.4
Fetal Kidney	5.9	Pituitary gland Pool	0.9
Renal ca. 786-0	0.1	Salivary Gland	0.0
Renal ca. A498	0.0	Thyroid (female)	2.6
Renal ca. ACHN	0.0	Pancreatic ca. CAPAN2	0.3
Renal ca. UO-31	2.7	Pancreas Pool	1.3

[0772]

TABLE LC
Panel 5 Islet
	Rel.		Rel.
	Exp. ()		Exp. (%)
	Ag6685,		Ag6685,
	Run		Run
Tissue Name	279519420	Tissue Name	279519420
97457_Patient-02go_adipose	11.8	94709_Donor 2 AM - A_adipose	25.3
97476_Patient-07sk_skeletal	0.0	94710_Donor 2 AM - B_adipose	42.3
muscle
97477_Patient-07ut_uterus	23.3	94711_Donor 2 AM - C_adipose	12.5
97478_Patient-07pl_placenta	51.8	94712_Donor 2 AD - A_adipose	14.8
99167_Bayer Patient 1	43.8	94713_Donor 2 AD - B_adipose	15.9
97482_Patient-08ut_uterus	3.3	94714_Donor 2 AD - C_adipose	12.3
97483_Patient-08pl_placenta	58.6	94742_Donor 3 U - A_Mesenchymal	0.0
		Stem Cells
97486_Patient-09sk_skeletal	11.3	94743_Donor 3 U - B_Mesenchymal	0.0
muscle		Stem Cells
97487_Patient-09ut_uterus	61.6	94730_Donor 3 AM - A_adipose	0.0
97488_Patient-09pl_placenta	10.4	94731_Donor 3 AM - B_adipose	17.9
97492_Patient-10ut_uterus	23.2	94732_Donor 3 AM - C_adipose	0.0
97493_Patient-10pl_placenta	37.1	94733_Donor 3 AD - A_adipose	25.5
97495_Patient-11go_adipose	23.5	94734_Donor 3 AD - B_adipose	0.0
97496_Patient-11sk_skeletal	25.7	94735_Donor 3 AD - C_adipose	0.0
muscle
97497_Patient-11ut_uterus	2.1	77138_Liver_HepG2untreated	33.2
97498_Patient-11pl_placenta	25.2	73556_Heart_Cardiac stromal cells	0.0
		(primary)
97500_Patient-12go_adipose	36.9	81735_Small Intestine	10.8
97501_Patient-12sk_skeletal	8.8	72409_Kidney_Proximal Convoluted	24.7
muscle		Tubule
97502_Patient-12ut_uterus	25.9	82685_Small intestine_Duodenum	12.7
97503_Patient-12pl_placenta	12.2	90650_Adrenal_Adrenocortical	12.9
		adenoma
94721_Donor 2 U -	87.1	72410_Kidney_HRCE	0.0
A_Mesenchymal Stem Cells
94722_Donor 2 U -	45.7	72411_Kidney_HRE	0.0
B_Mesenchymal Stem Cells
94723_Donor 2 U -	100.0	73139_Uterus_Uterine smooth	24.8
C_Mesenchymal Stem Cells		muscle cells

[0773] General_screening_panel_v1.6 Summary: Ag6685 Highest expression of this gene is seen in the fetal lung (CT=27). Interestingly, this gene is expressed at much higher levels in the fetal tissue when compared to the level of expression in the adult lung (CT=35). This observation suggests that expression of this gene can be used to distinguish between the fetal and adult sources of this tissue. 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.

[0774] Panel 5 Islet Summary: Ag6685 Expression of this gene on this panel is limited to samples derived from mesenchymal stem cells (CTs=34). 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 cells.

[0775] M. CG162509-02: Leukocyte-Associated IG-Like Receptor-2-Like Protein.

[0776] Expression of gene CG162509-02 was assessed using the primer-probe set Ag5910, described in Table MA. Results of the RTQ-PCR runs are shown in Tables MB, MC, MD and ME.

TABLE MA
Probe Name Ag5910
			Start	Seq ID
Primers		Length	Position	No
Forward	5′-agctgctggtgaaagaaagc-3′	20	362	221
Probe	TET-5′-ctcctcagctgggactgtgccag-3′-TAMRA	23	417	222
Reverse	5′-caaatccggaggcttcag-3′	18	443	223

[0777]

TABLE MB
AI_comprehensive panel_v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag5910,		Ag5910,
	Run		Run
Tissue Name	247842189	Tissue Name	247842189
110967 COPD-F	9.0	112427 Match Control Psoriasis-F	12.9
110980 COPD-F	3.4	112418 Psoriasis-M	4.2
110968 COPD-M	21.8	112723 Match Control Psoriasis-M	0.0
110977 COPD-M	11.2	112419 Psoriasis-M	9.5
110989 Emphysema-F	14.2	112424 Match Control Psoriasis-M	13.0
110992 Emphysema-F	10.4	112420 Psoriasis-M	11.3
110993 Emphysema-F	0.0	112425 Match Control Psoriasis-M	9.3
110994 Emphysema-F	0.0	104689 (MF) OA Bone-Backus	39.2
110995 Emphysema-F	4.7	104690 (MF) Adj “Normal”	58.2
		Bone-Backus
110996 Emphysema-F	4.2	104691 (MF) OA Synovium-	36.1
		Backus
110997 Asthma-M	4.0	104692 (BA) OA Cartilage-Backus	2.8
111001 Asthma-F	3.5	104694 (BA) OA Bone-Backus	18.7
111002 Asthma-F	5.0	104695 (BA) Adj “Normal”	24.5
		Bone-Backus
111003 Atopic Asthma-F	13.6	104696 (BA) OA Synovium-	30.4
		Backus
111004 Atopic Asthma-F	6.7	104700 (SS) OA Bone-Backus	19.9
111005 Atopic Asthma-F	9.6	104701 (SS) Adj “Normal”	28.1
		Bone-Backus
111006 Atopic Asthma-F	0.0	104702 (SS) OA Synovium-	45.1
		Backus
111417 Allergy-M	2.5	117093 OA Cartilage Rep7	7.3
112347 Allergy-M	0.0	112672 OA Bone5	14.0
112349 Normal Lung-F	0.0	112673 OA Synovium5	6.8
112357 Normal Lung-F	0.0	112674 OA Synovial Fluid cells5	2.4
112354 Normal Lung-M	0.0	117100 OA Cartilage Rep14	3.4
112374 Crohns-F	0.0	112756 OA Bone9	44.1
112389 Match Control Crohns-F	1.3	112757 OA Synovium9	0.0
112375 Crohns-F	3.3	112758 OA Synovial Fluid Cells9	2.5
112732 Match Control Crohns-F	28.7	117125 RA Cartilage Rep2	3.3
112725 Crohns-M	0.0	113492 Bone2 RA	19.8
112387 Match Control	6.9	113493 Synovium2 RA	12.8
Crohns-M
112378 Crohns-M	0.0	113494 Syn Fluid Cells RA	14.4
112390 Match Control	5.4	113499 Cartilage4 RA	29.5
Crohns-M
112726 Crohns-M	2.3	113500 Bone4 RA	17.0
112731 Match Control	8.4	113501 Synovium4 RA	43.8
Crohns-M
112380 Ulcer Col-F	0.0	113502 Syn Fluid Cells4 RA	18.4
112734 Match Control Ulcer	100.0	113495 Cartilage3 RA	16.7
Col-F
112384 Ulcer Col-F	3.5	113496 Bone3 RA	34.2
112737 Match Control Ulcer	0.0	113497 Synovium3 RA	5.9
Col-F
112386 Ulcer Col-F	0.0	113498 Syn Fluid Cells3 RA	15.9
112738 Match Control Ulcer	9.3	117106 Normal Cartilage Rep20	0.0
Col-F
112381 Ulcer Col-M	0.0	113663 Bone3 Normal	0.0
112735 Match Control Ulcer	0.0	113664 Synovium3 Normal	0.0
Col-M
112382 Ulcer Col-M	0.0	113665 Syn Fluid Cells3 Normal	1.1
112394 Match Control Ulcer	0.0	117107 Normal Cartilage Rep22	0.0
Col-M
112383 Ulcer Col-M	8.7	113667 Bone4 Normal	5.3
112736 Match Control Ulcer	2.2	113668 Synovium4 Normal	0.0
Col-M
112423 Psoriasis-F	0.0	113669 Syn Fluid Cells4 Normal	8.6

[0778]

TABLE MC
General_screening_panel_v1.5
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag5910,		Ag5910,
	Run		Run
Tissue Name	247583780	Tissue Name	247583780
Adipose	4.3	Renal ca. TK-10	3.9
Melanoma* Hs688(A).T	0.0	Bladder	10.0
Melanoma* Hs688(B).T	0.0	Gastric ca. (liver met.) NCI-N87	0.0
Melanoma* M14	0.0	Gastric ca. KATO III	0.2
Melanoma* LOXIMVI	0.0	Colon ca. SW-948	0.0
Melanoma* SK-MEL-5	0.2	Colon ca. SW480	0.2
Squamous cell carcinoma SCC-4	0.0	Colon ca.* (SW480 met) SW620	0.0
Testis Pool	1.0	Colon ca. HT29	0.0
Prostate ca.* (bone met) PC-3	0.0	Colon ca. HCT-116	0.0
Prostate Pool	1.4	Colon ca. CaCo-2	0.0
Placenta	5.6	Colon cancer tissue	100.0
Uterus Pool	0.2	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	0.6
Ovarian ca. OVCAR-5	0.0	Small Intestine Pool	0.3
Ovarian ca. IGROV-1	0.0	Stomach Pool	1.5
Ovarian ca. OVCAR-8	0.0	Bone Marrow Pool	0.4
Ovary	0.5	Fetal Heart	0.2
Breast ca. MCF-7	0.0	Heart Pool	0.6
Breast ca. MDA-MB-231	0.1	Lymph Node Pool	1.2
Breast ca. BT 549	0.0	Fetal Skeletal Muscle	0.7
Breast ca. T47D	0.0	Skeletal Muscle Pool	1.1
Breast ca. MDA-N	0.0	Spleen Pool	5.7
Breast Pool	1.0	Thymus Pool	6.1
Trachea	0.4	CNS cancer (glio/astro)	0.0
		U87-MG
Lung	0.5	CNS cancer (glio/astro)	0.0
		U-118-MG
Fetal Lung	2.4	CNS cancer (neuro; met)	0.0
		SK-N-AS
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-539	0.1
Lung ca. LX-1	2.7	CNS cancer (astro) SNB-75	0.0
Lung ca. NCI-H146	0.0	CNS cancer (glio) SNB-19	0.0
Lung ca. SHP-77	1.8	CNS cancer (glio) SF-295	0.0
Lung ca. A549	0.0	Brain (Amygdala) Pool	1.8
Lung ca. NCI-H526	0.0	Brain (cerebellum)	0.9
Lung ca. NCI-H23	0.3	Brain (fetal)	0.5
Lung ca. NCI-H460	0.0	Brain (Hippocampus) Pool	3.1
Lung ca. HOP-62	0.0	Cerebral Cortex Pool	1.6
Lung ca. NCI-H522	0.0	Brain (Substantia nigra) Pool	1.4
Liver	0.1	Brain (Thalamus) Pool	3.6
Fetal Liver	0.6	Brain (whole)	0.2
Liver ca. HepG2	4.5	Spinal Cord Pool	2.1
Kidney Pool	2.4	Adrenal Gland	2.0
Fetal Kidney	0.0	Pituitary gland Pool	1.9
Renal ca. 786-0	0.0	Salivary Gland	0.1
Renal ca. A498	0.0	Thyroid (female)	0.2
Renal ca. ACHN	0.0	Pancreatic ca. CAPAN2	0.0
Renal ca. UO-31	0.0	Pancreas Pool	1.6

[0779]

TABLE MD
Panel 4.1D
	Rel.		Rel.
	Exp. ()		Exp. (%)
	Ag5910,		Ag5910,
	Run		Run
Tissue Name	247578007	Tissue Name	247578007
Secondary Th1 act	28.3	HUVEC IL-1beta	0.0
Secondary Th2 act	100.0	HUVEC IFN gamma	0.0
Secondary Tr1 act	19.5	HUVEC TNF alpha + IFN gamma	0.0
Secondary Th1 rest	1.4	HUVEC TNF alpha + IL4	0.0
Secondary Th2 rest	1.8	HUVEC IL-11	0.0
Secondary Tr1 rest	1.2	Lung Microvascular EC none	0.0
Primary Th1 act	0.0	Lung Microvascular EC TNF	0.0
		alpha + IL-1beta
Primary Th2 act	31.0	Microvascular Dermal EC none	0.0
Primary Tr1 act	20.9	Microsvasular Dermal EC	0.0
		TNF alpha + IL-1beta
Primary Th1 rest	1.0	Bronchial epithelium TNF alpha +	0.0
		IL1beta
Primary Th2 rest	2.9	Small airway epithelium none	0.0
Primary Tr1 rest	0.0	Small airway epithelium TNF	0.0
		alpha + IL-1beta
CD45RA CD4 lymphocyte act	2.6	Coronery artery SMC rest	0.0
CD45RO CD4 lymphocyte act	16.3	Coronery artery SMC TNF alpha +	0.0
		IL-1beta
CD8 lymphocyte act	0.6	Astrocytes rest	0.0
Secondary CD8 lymphocyte	2.8	Astrocytes TNF alpha + IL-1beta	0.0
rest
Secondary CD8 lymphocyte	2.0	KU-812 (Basophil) rest	0.0
act
CD4 lymphocyte none	1.0	KU-812 (Basophil)	0.2
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	3.3	CCD1106 (Keratinocytes) none	0.0
CH11
LAK cells rest	4.2	CCD1106 (Keratinocytes)	0.0
		TNF alpha + IL-1beta
LAK cells IL-2	7.6	Liver cirrhosis	0.0
LAK cells IL-2 + IL-12	1.7	NCI-H292 none	0.0
LAK cells IL-2 + IFN gamma	4.1	NCI-H292 IL-4	0.0
LAK cells IL-2 + IL-18	2.0	NCI-H292 IL-9	0.0
LAK cells PMA/ionomycin	5.4	NCI-H292 IL-13	0.0
NK Cells IL-2 rest	32.1	NCI-H292 IFN gamma	0.0
Two Way MLR 3 day	1.2	HPAEC none	0.0
Two Way MLR 5 day	0.0	HPAEC TNF alpha + IL-1beta	0.0
Two Way MLR 7 day	0.3	Lung fibroblast none	0.0
PBMC rest	0.9	Lung fibroblast TNF alpha +	0.0
		IL-1beta
PBMC PWM	0.0	Lung fibroblast IL-4	0.0
PBMC PHA-L	0.3	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	1.3	Dermal fibroblast CCD1070 rest	0.0
B lymphocytes CD40L and	1.2	Dermal fibroblast CCD1070 TNF	18.2
IL-4		alpha
EOL-1 dbcAMP	8.0	Dermal fibroblast CCD1070	0.0
		IL-1beta
EOL-1 dbcAMP	0.0	Dermal fibroblast IFN gamma	0.0
PMA/ionomycin
Dendritic cells none	3.6	Dermal fibroblast IL-4	0.0
Dendritic cells LPS	1.7	Dermal Fibroblasts rest	0.0
Dendritic cells anti-CD40	1.2	Neutrophils TNF a + LPS	0.5
Monocytes rest	0.3	Neutrophils rest	0.7
Monocytes LPS	53.2	Colon	0.5
Macrophages rest	1.8	Lung	0.0
Macrophages LPS	2.5	Thymus	0.3
HUVEC none	0.0	Kidney	0.5
HUVEC starved	0.0

[0780]

TABLE ME
Panel 5 Islet
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag5910,		Ag5910,
	Run		Run
Tissue Name	247609827	Tissue Name	247609827
97457_Patient-02go_adipose	10.7	94709_Donor 2 AM - A_adipose	3.9
97476_Patient-07sk_skeletal	3.0	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	100.0	94712_Donor 2 AD - A_adipose	6.6
99167_Bayer Patient 1	0.0	94713_Donor 2 AD - B_adipose	0.8
97482_Patient-08ut_uterus	8.8	94714_Donor 2 AD - C_adipose	18.9
97483_Patient-08pl_placenta	7.9	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	33.7	94731_Donor 3 AM - B_adipose	0.0
97492_Patient-10ut_uterus	6.3	94732_Donor 3 AM - C_adipose	3.0
97493_Patient-10pl_placenta	14.7	94733_Donor 3 AD - A_adipose	77.4
97495_Patient-11go_adipose	1.2	94734_Donor 3 AD - B_adipose	0.0
97496_Patient-11sk_skeletal	1.1	94735_Donor 3 AD - C_adipose	0.0
muscle
97497_Patient-11ut_uterus	1.1	77138_Liver_HepG2untreated	9.8
97498_Patient-11pl_placenta	2.0	73556_Heart_Cardiac stromal cells	0.0
		(primary)
97500_Patient-12go_adipose	7.1	81735_Small Intestine	25.9
97501_Patient-12sk_skeletal	6.4	72409_Kidney_Proximal Convoluted	0.0
muscle		Tubule
97502_Patient-12ut_uterus	1.7	82685_Small intestine_Duodenum	0.0
97503_Patient-12pl_placenta	2.3	90650_Adrenal_Adrenocortical	4.3
		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

[0781] AI_comprehensive panel_v1.0 Summary: Ag5910 Highest expression is seen in a match control sample of ulcerative colitis (CT=32.2). Low but significant levels of expression are seen in clusters of samples derived from OA and RA. Thus, modulation of this gene product may be useful in the treatment of these diseases.

[0782] General_screening_panel_v1.5 Summary: Ag5910 Highest expression is seen in a colon cancer tissue (CT=28.5). Thus, expression of this gene could be used to differentiate between this sample and other samples on this panel and as a marker of this disease.

[0783] Low but significant levels of expression are also seen in the hippocampus, cerebral cortex, substantia nigra, thalamus, pituitary, pancreas, adrenal, fetal skeletal muscle, and adipose. This expression suggests that this gene may be involved in the pathogenesis of diseases of these tissues.

[0784] Panel 4.1D Summary: Ag5910 Highest expression of this gene is seen in chronically activated Th2 cells (CT=29.7). Prominent levels of expression are also seen in chronically activated Th1 and Tr1 cells, as well as in acutely activated Th2 and Tr1 cells, CD45RO CD4 lymphocytes, LPS activated monocytes, and resting NK cells. Since lung inflammatory diseases such as asthma and chronic obstructive pulmonary diseases are mediated by Th2 cells, this protein may be involved in the lung pathology associated with these Th2 T cells. Therefore, therapeutics designed against the protein encoded by this gene may be useful for the treatment of lung inflammatory diseases. Meyaard et al. have proposed that the Leukocyte-associated IG-like receptor family, which includes LAIR-1 and LAIR-2, may be pivotal in regulation of the mucosal immune response (J Exp Med 2001 194(1): 107-12). Thus LAIR-2 encoded by this gene may function in vivo in the normal establishment of tolerance. Modulation of the function of this gene or LAIR-2 encoded by this gene with a therapeutic antibody directed to the extracellular domain or with a protein therapeutic comprising the extracellular domain may be useful under chosen conditions in the stimulation or suppression of the immune response. Such therapeutics may have beneficial effects in treating diseases such as asthma, IBD, psoriasis, and arthritis in which T cells are chronically stimulated.

[0785] Panel 5 Islet Summary: Ag5910 Highest expression is seen in the placenta (CT=32). Low but significant levels of expression are also seen in samples derived from adipose and small intestine.

[0786] N. CG162687-01: Membrane Protein-Like Protein.

[0787] Expression of gene CG1.62687-01 was assessed using the primer-probe set Ag5906, described in Table NA. Results of the RTQ-PCR runs are shown in Tables NB, NC and ND.

TABLE NA
Probe Name Ag5906
			Start	Seq ID
Primers		Length	Position	No
Forward	5′-gctgaatagcgtcttcctcttc-3′	122	1887	224
Probe	TET-5′-ccttctacatcaagaagtacaccctcctga-3′-TAMRA	30	1913	225
Reverse	5′-cgaagatgccctggagtt-3′	18	1945	226

[0788]

TABLE NB
AI_comprehensive_panel_v1.0
	Rel.	Rel.		Rel.	Rel.
	Exp.(%)	Exp.(%)		Exp.(%)	Exp.(%)
	Ag5906,	Ag5906,		Ag5906,	Ag5906,
	Run	Run		Run	Run
Tissue Name	247682906	256261784	Tissue Name	247682906	256261784
110967 COPD-F	1.4	2.5	112427 Match Control	3.0	1.9
			Psoriasis-F
110980 COPD-F	0.7	1.4	112418 Psoriasis-M	0.7	1.9
110968 COPD-M	1.4	3.1	112723 Match Control	0.1	1.1
			Psoriasis-M
110977 COPD-M	2.7	4.1	112419 Psoriasis-M	2.2	1.4
110989	2.1	4.0	112424 Match Control	0.3	0.8
Emphysema-F			Psoriasis-M
110992	2.5	3.6	112420 Psoriasis-M	4.0	7.1
Emphysema-F
110993	2.0	2.6	112425 Match Control	3.0	2.1
Emphysema-F			Psoriasis-M
110994	0.9	0.1	104689 (MF) OA	5.9	7.2
Emphysema-F			Bone-Backus
110995	7.7	11.7	104690 (MF) Adj	2.1	2.7
Emphysema-F			“Normal”
			Bone-Backus
110996	2.1	1.1	104691 (MF) OA	3.5	3.8
Emphysema-F			Synovium-Backus
110997 Asthma-M	2.7	1.5	104692 (BA) OA	0.1	0.1
			Cartilage-Backus
111001 Asthma-F	2.2	0.8	104694 (BA) OA	1.9	3.1
			Bone-Backus
111002 Asthma-F	2.7	4.8	104695 (BA) Adj	1.7	0.7
			“Normal”
			Bone-Backus
111003 Atopic	2.4	1.8	104696 (BA) OA	2.4	1.1
Asthma-F			Synovium-Backus
111004 Atopic	1.3	3.2	104700 (SS) OA	5.7	7.3
Asthma-F			Bone-Backus
111005 Atopic	0.8	1.8	104701 (SS) Adj	2.0	3.4
Asthma-F			“Normal”
			Bone-Backus
111006 Atopic	0.1	4.7	104702 (SS) OA	1.8	4.8
Asthma-F			Synovium-Backus
111417 Allergy-M	0.8	1.7	117093 OA Cartilage	2.1	2.9
			Rep7
112347 Allergy-M	0.0	0.0	112672 OA Bone5	5.3	7.3
112349 Normal	0.0	0.0	112673 OA	1.5	1.9
Lung-F			Synovium5
112357 Normal	0.5	1.8	112674 OA Synovial	1.7	3.6
Lung-F			Fluid cells5
112354 Normal	0.3	0.4	117100 OA Cartilage	1.1	1.4
Lung-M			Rep14
112374 Crohns-F	0.9	0.6	112756 OA Bone9	1.5	2.7
112389 Match	1.0	2.0	112757 OA	0.7	0.5
Control Crohns-F			Synovium9
112375 Crohns-F	0.6	0.4	112758 OA Synovial	1.2	2.2
			Fluid Cells9
112732 Match	57.4	90.1	117125 RA Cartilage	1.7	1.8
Control Crohns-F			Rep2
112725 Crohns-M	0.2	0.7	113492 Bone2 RA	2.8	7.9
112387 Match	0.7	1.6	113493 Synovium2	1.8	2.2
Control Crohns-M			RA
112378 Crohns-M	0.0	0.0	113494 Syn Fluid	3.8	3.0
			Cells RA
112390 Match	1.8	3.2	113499 Cartilage4 RA	4.0	7.3
Control Crohns-M
112726 Crohns-M	0.6	3.2	113500 Bone4 RA	4.5	7.6
112731 Match	1.0	2.4	113501 Synovium4	2.3	3.4
Control Crohns-M			RA
112380 Ulcer	1.0	1.7	113502 Syn Fluid	1.8	1.7
Col-F			Cells4 RA
112734 Match	100.0	100.0	113495 Cartilage3 RA	2.4	3.6
Control Ulcer
Col-F
112384 Ulcer	6.8	14.1	113496 Bone3 RA	4.4	5.8
Col-F
112737 Match	0.8	0.4	113497 Synovium3	2.7	3.0
Control Ulcer			RA
Col-F
112386 Ulcer	0.0	0.9	113498 Syn Fluid	3.6	18.3
Col-F			Cells3 RA
112738 Match	2.1	4.2	117106 Normal	1.4	0.3
Control Ulcer			Cartilage Rep20
Col-F
112381 Ulcer	0.1	0.0	113663 Bone3 Normal	2.8	0.0
Col-M
112735 Match	0.7	1.2	113664 Synovium3	0.0	0.0
Control Ulcer			Normal
Col-M
112382 Ulcer	1.3	1.5	113665 Syn Fluid	0.1	0.0
Col-M			Cells3 Normal
112394 Match	0.4	0.1	117107 Normal	0.1	1.0
Control Ulcer			Cartilage Rep22
Col-M
112383 Ulcer	3.8	3.8	113667 Bone4 Normal	0.5	1.0
Col-M
112736 Match	1.0	1.6	113668 Synovium4	0.9	1.0
Control Ulcer			Normal
Col-M
112423 Psoriasis-F	0.9	1.7	113669 Syn Fluid	2.2	3.0
			Cells4 Normal

[0789]

TABLE NC
General_screening_panel_v1.5
	Rel.	Rel.		Rel.	Rel.
	Exp.(%)	Exp.(%)		Exp.(%)	Exp.(%)
	Ag5906,	Ag5906,		Ag5906,	Ag5906,
	Run	Run		Run	Run
Tissue Name	247453559	255877137	Tissue Name	247453559	255877137
Adipose	7.3	8.1	Renal ca. TK-10	4.7	8.0
Melanoma*	0.0	0.0	Bladder	15.1	17.2
Hs688(A).T
Melanoma*	0.0	0.0	Gastric ca. (liver	7.5	9.1
Hs688(B).T			met.) NCI-N87
Melanoma* M14	0.3	0.1	Gastric ca. KATO	13.1	18.0
			III
Melanoma*	0.2	0.1	Colon ca. SW-948	1.3	1.6
LOXIMVI
Melanoma*	1.6	2.3	Colon ca. SW480	6.4	11.0
SK-MEL-5
Squamous cell	0.2	0.4	Colon ca.* (SW480	3.2	2.6
carcinoma SCC-4			met) SW620
Testis Pool	1.6	1.6	Colon ca. HT29	9.5	10.3
Prostate ca.* (bone	0.0	0.4	Colon ca. HCT-116	5.0	9.0
met) PC-3
Prostate Pool	3.8	3.2	Colon ca. CaCo-2	0.0	0.2
Placenta	5.1	7.0	Colon cancer tissue	22.7	23.0
Uterus Pool	1.4	0.9	Colon ca. SW1116	0.0	0.1
Ovarian ca.	4.8	3.8	Colon ca. Colo-205	1.1	0.7
OVCAR-3
Ovarian ca. SK-OV-3	0.0	0.0	Colon ca. SW-48	1.2	1.3
Ovarian ca.	0.0	0.2	Colon Pool	5.6	6.0
OVCAR-4
Ovarian ca.	66.9	80.1	Small Intestine Pool	6.3	3.8
OVCAR-5
Ovarian ca.	0.5	0.2	Stomach Pool	4.7	5.0
IGROV-1
Ovarian ca.	0.3	0.4	Bone Marrow Pool	6.1	3.9
OVCAR-8
Ovary	2.6	3.2	Fetal Heart	2.0	2.6
Breast ca. MCF-7	1.0	0.8	Heart Pool	2.2	2.2
Breast ca.	2.7	2.0	Lymph Node Pool	9.0	7.1
MDA-MB-231
Breast ca. BT 549	0.0	0.0	Fetal Skeletal	2.6	2.5
			Muscle
Breast ca. T47D	5.3	4.2	Skeletal Muscle	0.7	0.6
			Pool
Breast ca. MDA-N	0.2	0.4	Spleen Pool	52.9	100.0
Breast Pool	4.4	6.6	Thymus Pool	100.0	76.8
Trachea	9.8	14.2	CNS cancer	0.0	0.1
			(glio/astro)
			U-87-MG
Lung	0.7	0.6	CNS cancer	0.0	0.0
			(glio/astro)
			U-118-MG
Fetal Lung	23.0	20.6	CNS cancer	0.0	0.2
			(neuro; met)
			SK-N-AS
Lung ca. NCI-N417	0.0	0.0	CNS cancer (astro)	0.0	0.0
			SF-539
Lung ca. LX-1	14.1	16.2	CNS cancer (astro)	0.0	0.1
			SNB-75
Lung ca. NCI-H146	0.0	0.2	CNS cancer (glio)	0.3	0.3
			SNB-19
Lung ca. SHP-77	1.1	1.4	CNS cancer (glio)	0.0	0.1
			SF-295
Lung ca. A549	0.3	0.2	Brain (Amygdala)	1.8	3.3
			Pool
Lung ca. NCI-H526	0.0	0.2	Brain (cerebellum)	1.8	2.1
Lung ca. NCI-H23	1.2	1.2	Brain (fetal)	3.3	3.0
Lung ca. NCI-H460	0.0	0.2	Brain	3.8	3.9
			(Hippocampus)
			Pool
Lung ca. HOP-62	2.6	4.6	Cerebral Cortex	1.0	1.4
			Pool
Lung ca. NCI-H522	0.0	0.1	Brain (Substantia	2.5	3.8
			nigra) Pool
Liver	2.9	4.0	Brain (Thalamus)	5.3	3.8
			Pool
Fetal Liver	44.4	49.0	Brain (whole)	3.8	2.1
Liver ca. HepG2	16.3	16.7	Spinal Cord Pool	7.9	4.5
Kidney Pool	8.4	10.5	Adrenal Gland	4.5	4.4
Fetal Kidney	1.7	2.2	Pituitary gland Pool	0.0	0.3
Renal ca. 786-0	0.0	0.0	Salivary Gland	7.3	5.7
Renal ca. A498	0.0	0.0	Thyroid (female)	1.8	2.9
Renal ca. ACHN	0.0	0.4	Pancreatic ca.	2.1	2.7
			CAPAN2
Renal ca. UO-31	1.1	1.7	Pancreas Pool	12.9	15.6

[0790]

TABLE ND
Panel 4.1D
	Rel.	Rel.		Rel.	Rel.
	Exp.(%)	Exp.(%)		Exp.(%)	Exp.(%)
	Ag5906,	Ag5906,		Ag5906,	Ag5906,
	Run	Run		Run	Run
Tissue Name	247576174	255877310	Tissue Name	247576174	255877310
Secondary Th1 act	47.6	60.3	HUVEC IL-1beta	0.0	0.0
Secondary Th2 act	66.4	84.7	HUVEC IFN gamma	0.0	0.0
Secondary Tr1 act	18.7	52.9	HUVEC TNF alpha +	0.0	0.0
			IFN gamma
Secondary Th1 rest	0.8	20.3	HUVEC TNF alpha +	0.0	0.0
			IL4
Secondary Th2 rest	2.8	19.2	HUVEC IL-11	0.1	0.1
Secondary Tr1 rest	2.7	27.4	Lung Microvascular	0.0	0.3
			EC none
Primary Th1 act	0.3	8.0	Lung Microvascular	0.0	0.0
			EC TNF alpha +
			IL-1beta
Primary Th2 act	54.3	52.9	Microvascular	0.0	0.0
			Dermal EC none
Primary Tr1 act	41.2	46.7	Microsvasular	0.0	0.0
			Dermal EC
			TNF alpha + IL-1beta
Primary Th1 rest	3.6	11.1	Bronchial epithelium	0.0	0.0
			TNF alpha + IL1beta
Primary Th2 rest	12.3	19.5	Small airway	0.1	0.0
			epithelium none
Primary Tr1 rest	2.9	14.9	Small airway
			epithelium TNF alpha +	0.0	0.0
			IL-1beta
CD45RA CD4	27.5	28.7	Coronery artery SMC	0.0	0.0
lymphocyte act			rest
CD45RO CD4	58.6	59.5	Coronery artery SMC	0.0	0.0
lymphocyte act			TNF alpha + IL-1beta
CD8 lymphocyte act	4.8	21.5	Astrocytes rest	0.0	0.0
Secondary CD8	34.2	25.3	Astrocytes TNF alpha +	0.0	0.0
lymphocyte rest			IL-1beta
Secondary CD8	3.7	10.6	KU-812 (Basophil)	15.7	22.7
lymphocyte act			rest
CD4 lymphocyte none	5.0	24.1	KU-812 (Basophil)	19.1	27.9
			PMA/ionomycin
2ry	11.3	32.8	CCD1106	0.4	0.5
Th1/Th2/Tr1_anti-CD95			(Keratinocytes) none
CH11
LAK cells rest	12.0	18.8	CCD1106	0.0	0.1
			(Keratinocytes)
			TNF alpha + IL-1beta
LAK cells IL-2	10.4	24.7	Liver cirrhosis	0.9	1.6
LAK cells IL-2 + IL-12	1.7	3.9	NCI-H292 none	0.1	0.2
LAK cells IL-2 + IFN	7.7	11.3	NCI-H292 IL-4	0.1	0.1
gamma
LAK cells IL-2 + IL-18	4.4	11.4	NCI-H292 IL-9	0.2	0.0
LAK cells	15.7	15.5	NCI-H292 IL-13	0.4	0.2
PMA/ionomycin
NK Cells IL-2 rest	100.0	100.0	NCI-H292 IFN	0.1	0.2
			gamma
Two Way MLR 3 day	6.7	15.3	HPAEC none	0.1	0.1
Two Way MLR 5 day	1.7	7.9	HPAEC TNF alpha +	0.1	0.1
			IL-1beta
Two Way MLR 7 day	4.2	7.1	Lung fibroblast none	0.0	0.0
PBMC rest	2.9	14.1	Lung fibroblast TNF	0.0	0.0
			alpha + IL-1beta
PBMC PWM	4.0	8.7	Lung fibroblast IL-4	0.0	0.0
PBMC PHA-L	5.6	18.3	Lung fibroblast IL-9	0.0	0.0
Ramos (B cell) none	2.1	6.6	Lung fibroblast IL-13	0.0	0.0
Ramos (B cell)	25.7	31.9	Lung fibroblast IFN	0.0	0.0
ionomycin			gamma
B lymphocytes PWM	17.2	15.3	Dermal fibroblast	0.0	0.0
			CCD1070 rest
B lymphocytes CD40L	42.6	54.3	Dermal fibroblast	61.6	82.9
and IL-4			CCD1070 TNF alpha
EOL-1 dbcAMP	5.1	4.8	Dermal fibroblast	0.0	0.0
			CCD1070 IL-1beta
EOL-1 dbcAMP	0.8	6.2	Dermal fibroblast	0.0	0.0
PMA/ionomycin			IFN gamma
Dendritic cells none	9.0	14.7	Dermal fibroblast	0.0	0.0
			IL-4
Dendritic cells LPS	0.2	0.9	Dermal Fibroblasts	0.0	0.0
			rest
Dendritic cells	1.0	4.5	Neutrophils	1.5	3.1
anti-CD40			TNFa + LPS
Monocytes rest	1.3	11.4	Neutrophils rest	13.4	14.0
Monocytes LPS	1.3	1.9	Colon	0.2	0.4
Macrophages rest	2.4	3.4	Lung	0.3	0.2
Macrophages LPS	0.3	0.2	Thymus	6.3	9.0
HUVEC none	0.0	0.0	Kidney	0.2	0.2
HUVEC starved	0.0	0.0

[0791] AI_comprehensive panel_v1.0 Summary: Ag5906 Two experiments with the same probe and primer produce results that are in excellent agreement. Highest expression is seen in a match control sample from ulcerative colitis (CTs=27-28), with prominent expression also seen in a match control sample from Crohn's. 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 diseases. Modulation of the expression or function of this gene may also be useful for the treatment of ulcerative colitis and Crohn's disease.

[0792] General_screening_panel_v1.5 Summary: Ag5906 Two experiments with the same probe and primer produce results that are in very good agreement. Highest expression is seen in the spleen and thymus (CTs=28-30). Moderate levels of expression are also seen in an ovarian cancer cell line and fetal liver, with low but significant expression seen in adipose, thyroid, pancreas, adrenal, thyroid, and regions of the brain, including cerebellum, cerebral cortex, amygdala, hippocampus, thalamus, and substantia nigra.

[0793] Therefore, expression of this gene maybe used to identify thymic and splenic tissue. Furthermore, drugs that inhibit the function of this protein may regulate T cell development in the thymus and reduce or eliminate the symptoms of T cell mediated autoimmune or inflammatory diseases, including asthma, allergies, inflammatory bowel disease, lupus erythematosus, or rheumatoid arthritis. Additionally, small molecule or antibody therapeutics designed against this putative protein may disrupt T cell development in the thymus and function as an immunosuppresant for tissue transplant.

[0794] The expression profile suggests that this gene product may also be involved in metabolic and neurodegenerative diseases, such as obesity, diabetes, Parkinson's, and Alzheimer's.

[0795] Panel 4.1D Summary: Ag5906 Two experiments with the same probe and primer produce results that are in excellent agreement. Highest expression is seen in resting NK cells (CTs=28). This gene is also expressed by T lymphocytes prepared under a number of conditions at moderate levels, B cells, LAK cells, dendritic cells, basophils, monocytes, macrophages, and TNF-a treated dermal fibroblasts. Therefore, therapeutics designed with the protein encoded by this transcript may help to regulate T cell function and be effective in treating T cell mediated diseases such as asthma, arthritis, psoriasis, IBD, and lupus.

[0796] O. CG162738-01: Splice Variant of MADSO1-Like Protein.

[0797] Expression of gene CG162738-01 was assessed using the primer-probe set Ag5851, described in Table OA.

TABLE OA
Probe Name Ag5851
			Start	Seq ID
Primers		Length	Position	No
Forward	5′-gccgtcagaaaggaaacagt-3′	20	1014	217
Probe	TET-5′-tttcatcagttgcattttccaggctg-3′-TAMRA	26	1039	228
Reverse	5′-gtcacagtccaaaatgttttatacag-3′	26	1069	229

[0798] P. CG162738-02: Splice Variant of MADSO1-Like Protein.

[0799] Expression of gene CG162738-02 was assessed using the primer-probe set Ag5860, described in Table PA.

TABLE PA
Probe Name Ag5860
			Start	Seq ID
Primers		Length	Position	No
Forward	5′-gagcagttcatcgcaggaag-3′	20	381	230
Probe	TET-5′-tgggagtacaggagctgatcaatacacg-3′-TAMRA	28	553	231
Reverse	5′-cagtgaggactcgtgcttgtc-3′	21	582	232

[0800] Q. CG163175-01: Type Ib Membrane Protein-Like Protein.

[0801] Expression of gene CG163175-01 was assessed using the primer-probe set Ag5907, described in Table QA. Results of the RTQ-PCR runs are shown in Tables QB, QC, QD, QE and QF.

TABLE QA
Probe Name Ag5907
			Start	Seq ID
Primers		Length	Position	No
Forward	5′-gtaaaccgactgtccaagttactg-3′	24	1004	233
Probe	TET-5′-ccatagtctcgaaataacagcattcccc-3′-TAMRA	128	1035	234
Reverse	5′-taaaacgaagctgagtcttatcatatct-3′	128	1064	235

[0802]

TABLE QB
AI_comprehensive_panel_v1.0
	Rel.		Rel.
	Exp.(%)		Exp.(%)
	Ag5907,		Ag5907,
	Run		Run
Tissue Name	247842186	Tissue Name	247842186
110967 COPD-F	34.6	112427 Match Control Psoriasis-F	65.1
110980 COPD-F	44.8	112418 Psoriasis-M	30.4
110968 COPD-M	27.7	112723 Match Control Psoriasis-M	8.6
110977 COPD-M	66.0	112419 Psoriasis-M	50.3
110989 Emphysema-F	64.6	112424 Match Control Psoriasis-M	22.7
110992 Emphysema-F	26.4	112420 Psoriasis-M	76.8
110993 Emphysema-F	38.4	112425 Match Control Psoriasis-M	60.7
110994 Emphysema-F	17.0	104689 (MF) OA Bone-Backus	51.8
110995 Emphysema-F	77.9	104690 (MF) Adj “Normal”	33.0
		Bone-Backus
110996 Emphysema-F	13.1	104691 (MF) OA Synovium-Backus	42.3
110997 Asthma-M	13.2	104692 (BA) OA Cartilage-Backus	18.2
111001 Asthma-F	48.6	104694 (BA) OA Bone-Backus	36.3
111002 Asthma-F	45.7	104695 (BA) Adj “Normal”	30.1
		Bone-Backus
111003 Atopic Asthma-F	27.4	104696 (BA) OA Synovium-Backus	44.4
111004 Atopic Asthma-F	42.6	104700 (SS) OA Bone-Backus	12.7
111005 Atopic Asthma-F	33.2	104701 (SS) Adj “Normal”	30.4
		Bone-Backus
111006 Atopic Asthma-F	8.7	104702 (SS) OA Synovium-Backus	64.2
111417 Allergy-M	28.5	117093 OA Cartilage Rep7	49.3
112347 Allergy-M	15.4	112672 OA Bone5	57.4
112349 Normal Lung-F	15.5	112673 OA Synovium5	17.1
112357 Normal Lung-F	53.2	112674 OA Synovial Fluid cells5	24.5
112354 Normal Lung-M	19.6	117100 OA Cartilage Rep14	10.1
112374 Crohns-F	21.8	112756 OA Bone9	76.3
112389 Match Control Crohns-F	44.1	112757 OA Synovium9	14.3
112375 Crohns-F	16.2	112758 OA Synovial Fluid Cells9	21.3
112732 Match Control Crohns-F	47.3	117125 RA Cartilage Rep2	47.3
112725 Crohns-M	8.1	113492 Bone2 RA	20.2
112387 Match Control	16.0	113493 Synovium2 RA	8.6
Crohns-M
112378 Crohns-M	16.5	113494 Syn Fluid Cells RA	13.4
112390 Match Control	58.2	113499 Cartilage4 RA	15.8
Crohns-M
112726 Crohns-M	41.2	113500 Bone4 RA	17.7
112731 Match Control	29.5	113501 Synovium4 RA	14.0
Crohns-M
112380 Ulcer Col-F	35.6	113502 Syn Fluid Cells4 RA	8.1
112734 Match Control Ulcer	100.0	113495 Cartilage3 RA	14.6
Col-F
112384 Ulcer Col-F	78.5	113496 Bone3 RA	11.2
112737 Match Control Ulcer	20.3	113497 Synovium3 RA	9.9
Col-F
112386 Ulcer Col-F	4.9	113498 Syn Fluid Cells3 RA	18.3
112738 Match Control Ulcer	19.6	117106 Normal Cartilage Rep20	5.1
Col-F
112381 Ulcer Col-M	12.9	113663 Bone3 Normal	14.3
112735 Match Control Ulcer	33.0	113664 Synovium3 Normal	5.6
Col-M
112382 Ulcer Col-M	44.8	113665 Syn Fluid Cells3 Normal	8.0
112394 Match Control Ulcer	13.4	117107 Normal Cartilage Rep22	21.5
Col-M
112383 Ulcer Col-M	64.2	113667 Bone4 Normal	15.2
112736 Match Control Ulcer	21.9	113668 Synovium4 Normal	24.7
Col-M
112423 Psoriasis-F	29.7	113669 Syn Fluid Cells4 Normal	33.9

[0803]

TABLE QC
General_screening_panel_v1.5
	Rel.		Rel.
	Exp.(%)		Exp.(%)
	Ag5907,		Ag5907,
	Run		Run
Tissue Name	248163366	Tissue Name	248163366
Adipose	8.9	Renal ca. TK-10	45.4
Melanoma* Hs688(A).T	19.8	Bladder	13.9
Melanoma* Hs688(B).T	23.8	Gastric ca. (liver met.) NCI-N87	36.6
Melanoma* M14	36.9	Gastric ca. KATO III	58.6
Melanoma* LOXIMVI	56.6	Colon ca. SW-948	26.4
Melanoma* SK-MEL-5	30.8	Colon ca. SW480	49.7
Squamous cell carcinoma SCC-4	28.1	Colon ca.* (SW480 met) SW620	35.4
Testis Pool	14.2	Colon ca. HT29	13.5
Prostate ca.* (bone met) PC-3	19.8	Colon ca. HCT-116	100.0
Prostate Pool	16.2	Colon ca. CaCo-2	53.2
Placenta	1.7	Colon cancer tissue	17.4
Uterus Pool	15.1	Colon ca. SW1116	14.7
Ovarian ca. OVCAR-3	27.9	Colon ca. Colo-205	7.3
Ovarian ca. SK-OV-3	30.8	Colon ca. SW-48	7.6
Ovarian ca. OVCAR-4	19.5	Colon Pool	13.9
Ovarian ca. OVCAR-5	29.7	Small Intestine Pool	18.7
Ovarian ca. IGROV-1	22.4	Stomach Pool	12.3
Ovarian ca. OVCAR-8	7.3	Bone Marrow Pool	7.5
Ovary	8.9	Fetal Heart	7.1
Breast ca. MCF-7	27.7	Heart Pool	9.0
Breast ca. MDA-MB-231	56.3	Lymph Node Pool	25.9
Breast ca. BT 549	55.5	Fetal Skeletal Muscle	5.0
Breast ca. T47D	22.5	Skeletal Muscle Pool	18.2
Breast ca. MDA-N	24.3	Spleen Pool	22.1
Breast Pool	15.4	Thymus Pool	15.5
Trachea	9.0	CNS cancer (glio/astro) U87-MG	45.1
Lung	3.2	CNS cancer (glio/astro) U-118-MG	65.1
Fetal Lung	18.3	CNS cancer (neuro; met) SK-N-AS	28.7
Lung ca. NCI-N417	12.4	CNS cancer (astro) SF-539	15.7
Lung ca. LX-1	60.7	CNS cancer (astro) SNB-75	40.1
Lung ca. NCI-H146	7.9	CNS cancer (glio) SNB-19	17.1
Lung ca. SHP-77	17.4	CNS cancer (glio) SF-295	38.2
Lung ca. A549	53.2	Brain (Amygdala) Pool	15.8
Lung ca. NCI-H526	6.0	Brain (cerebellum)	27.5
Lung ca. NCI-H23	44.4	Brain (fetal)	18.0
Lung ca. NCI-H460	15.3	Brain (Hippocampus) Pool	17.8
Lung ca. HOP-62	10.0	Cerebral Cortex Pool	16.6
Lung ca. NCI-H522	60.7	Brain (Substantia nigra) Pool	12.6
Liver	1.0	Brain (Thalamus) Pool	23.0
Fetal Liver	17.1	Brain (whole)	7.7
Liver ca. HepG2	34.4	Spinal Cord Pool	17.9
Kidney Pool	28.3	Adrenal Gland	11.7
Fetal Kidney	15.6	Pituitary gland Pool	3.2
Renal ca. 786-0	15.4	Salivary Gland	1.8
Renal ca. A498	16.3	Thyroid (female)	3.3
Renal ca. ACHN	31.9	Pancreatic ca. CAPAN2	19.8
Renal ca. UO-31	29.9	Pancreas Pool	18.4

[0804]

TABLE QD
Panel 4.1D
	Rel.		Rel.
	Exp.()		Exp.(%)
	Ag5907,		Ag5907,
	Run		Run
Tissue Name	247576176	Tissue Name	247576176
Secondary Th1 act	31.6	HUVEC IL-1beta	38.4
Secondary Th2 act	38.4	HUVEC IFN gamma	38.2
Secondary Tr1 act	10.4	HUVEC TNF alpha + IFN gamma	2.6
Secondary Th1 rest	0.4	HUVEC TNF alpha + IL4	2.7
Secondary Th2 rest	0.4	HUVEC IL-11	20.7
Secondary Tr1 rest	0.7	Lung Microvascular EC none	54.7
Primary Th1 act	3.6	Lung Microvascular EC TNF alpha +	11.3
		IL-1beta
Primary Th2 act	32.8	Microvascular Dermal EC none	1.6
Primary Tr1 act	39.8	Microsvasular Dermal EC	8.5
		TNF alpha + IL-1beta
Primary Th1 rest	0.5	Bronchial epithelium TNF alpha +	14.8
		IL1beta
Primary Th2 rest	3.1	Small airway epithelium none	15.7
Primary Tr1 rest	1.0	Small airway epithelium TNF alpha +	40.1
		IL-1beta
CD45RA CD4 lymphocyte act	37.1	Coronery artery SMC rest	14.4
CD45RO CD4 lymphocyte act	84.7	Coronery artery SMC TNF alpha +	19.5
		IL-1beta
CD8 lymphocyte act	9.2	Astrocytes rest	2.8
Secondary CD8 lymphocyte rest	41.5	Astrocytes TNF alpha + IL-1beta	2.9
Secondary CD8 lymphocyte act	8.2	KU-812 (Basophil) rest	32.8
CD4 lymphocyte none	0.6	KU-812 (Basophil)	39.0
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	3.4	CCD1106 (Keratinocytes) none	60.3
CH11
LAK cells rest	9.9	CCD1106 (Keratinocytes)	28.1
		TNF alpha + IL-1beta
LAK cells IL-2	9.5	Liver cirrhosis	9.6
LAK cells IL-2 + IL-12	2.9	NCI-H292 none	19.6
LAK cells IL-2 + IFN gamma	5.6	NCI-H292 IL-4	33.0
LAK cells IL-2 + IL-18	4.5	NCI-H292 IL-9	40.1
LAK cells PMA/ionomycin	13.6	NCI-H292 IL-13	34.4
NK Cells IL-2 rest	27.2	NCI-H292 IFN gamma	14.8
Two Way MLR 3 day	8.0	HPAEC none	11.4
Two Way MLR 5 day	1.2	HPAEC TNF alpha + IL-1beta	34.4
Two Way MLR 7 day	6.9	Lung fibroblast none	21.3
PBMC rest	2.0	Lung fibroblast TNF alpha + IL-1	20.7
		beta
PBMC PWM	4.1	Lung fibroblast IL-4	19.5
PBMC PHA-L	5.9	Lung fibroblast IL-9	15.0
Ramos (B cell) none	14.2	Lung fibroblast IL-13	2.7
Ramos (B cell) ionomycin	100.0	Lung fibroblast IFN gamma	41.2
B lymphocytes PWM	64.2	Dermal fibroblast CCD1070 rest	40.3
B lymphocytes CD40L and IL-4	24.0	Dermal fibroblast CCD1070 TNF	41.5
		alpha
EOL-1 dbcAMP	35.1	Dermal fibroblast CCD1070 IL-1	13.5
		beta
EOL-1 dbcAMP	0.2	Dermal fibroblast IFN gamma	15.5
PMA/ionomycin
Dendritic cells none	7.0	Dermal fibroblast IL-4	39.5
Dendritic cells LPS	1.5	Dermal Fibroblasts rest	17.3
Dendritic cells anti-CD40	1.5	Neutrophils TNFa + LPS	0.2
Monocytes rest	0.1	Neutrophils rest	0.5
Monocytes LPS	11.8	Colon	1.5
Macrophages rest	3.5	Lung	0.9
Macrophages LPS	3.0	Thymus	2.7
HUVEC none	26.6	Kidney	18.0
HUVEC starved	22.1

[0805]

TABLE QE
Panel 5D
	Rel.		Rel.
	Exp.(%)		Exp.(%)
	Ag507,		Ag5907,
	Run		Run
Tissue Name	248193678	Tissue Name	248193678
97457_Patient-02go_adipose	45.1	94709_Donor 2 AM - A_adipose	39.0
97476_Patient-07sk_skeletal	35.4	94710_Donor 2 AM - B_adipose	23.5
muscle
97477_Patient-07ut_uterus	40.1	94711_Donor 2 AM - C_adipose	15.5
97478_Patient-07pl_placenta	14.7	94712_Donor 2 AD - A_adipose	41.5
97481_Patient-08sk_skeletal	40.3	94713_Donor 2 AD - B_adipose	50.7
muscle
97482_Patient-08ut_uterus	24.7	94714_Donor 2 AD - C_adipose	52.9
97483_Patient-08pl_placenta	5.3	94742_Donor 3 U - A_Mesenchymal	19.2
		Stem Cells
97486_Patient-09sk_skeletal	2.6	94743_Donor 3 U - B_Mesenchymal	19.9
muscle		Stem Cells
97487_Patient-09ut_uterus	35.4	94730_Donor 3 AM - A_adipose	47.3
97488_Patient-09pl_placenta	7.2	94731_Donor 3 AM - B_adipose	38.2
97492_Patient-10ut_uterus	48.3	94732_Donor 3 AM - C_adipose	26.6
97493_Patient-10pl_placenta	19.2	94733_Donor 3 AD - A_adipose	48.6
97495_Patient-11go_adipose	17.7	94734_Donor 3 AD - B_adipose	29.1
97496_Patient-11sk_skeletal	12.3	94735_Donor 3 AD - C_adipose	35.4
muscle
97497_Patient-11ut_uterus	39.0	77138_Liver_HepG2untreated	100.0
97498_Patient-11pl_placenta	15.6	73556_Heart_Cardiac stromal cells	24.8
		(primary)
97500_Patient-12go_adipose	32.3	81735_Small Intestine	49.7
97501_Patient-12sk_skeletal	29.7	72409_Kidney_Proximal Convoluted	13.6
muscle		Tubule
97502_Patient-12ut_uterus	50.0	82685_Small intestine_Duodenum	13.5
97503_Patient-12pl_placenta	10.0	90650_Adrenal_Adrenocortical	5.4
		adenoma
94721_Donor 2 U -	28.5	72410_Kidney_HRCE	62.0
A_Mesenchymal Stem Cells
94722_Donor 2 U -	13.8	72411_Kidney_HRE	37.1
B_Mesenchymal Stem Cells
94723_Donor 2 U -	16.2	73139_Uterus_Uterine smooth	9.0
C_Mesenchymal Stem Cells		muscle cells

[0806]

TABLE QF
general_oncology_screening_panel_v2.4
	Rel.		Rel.
	Exp.(%)		Exp.(%)
	Ag5907,		Ag5907,
	Run		Run
Tissue Name	260316170	Tissue Name	260316170
Colon cancer 1	21.3	Bladder cancer NAT 2	0.9
Colon cancer NAT 1	10.9	Bladder cancer NAT 3	0.2
Colon cancer 2	39.2	Bladder cancer NAT 4	5.6
Colon cancer NAT 2	8.2	Prostate adenocarcinoma 1	29.3
Colon cancer 3	43.2	Prostate adenocarcinoma 2	2.6
Colon cancer NAT 3	27.0	Prostate adenocarcinoma 3	6.4
Colon malignant cancer 4	77.4	Prostate adenocarcinoma 4	19.1
Colon normal adjacent tissue 4	3.3	Prostate cancer NAT 5	5.2
Lung cancer 1	12.4	Prostate adenocarcinoma 6	3.8
Lung NAT 1	0.5	Prostate adenocarcinoma 7	8.6
Lung cancer 2	90.8	Prostate adenocarcinoma 8	0.9
Lung NAT 2	3.1	Prostate adenocarcinoma 9	22.2
Squamous cell carcinoma 3	61.1	Prostate cancer NAT 10	2.4
Lung NAT 3	0.8	Kidney cancer 1	16.7
metastatic melanoma 1	10.4	KidneyNAT 1	7.9
Melanoma 2	3.3	Kidney cancer 2	100.0
Melanoma 3	4.3	Kidney NAT 2	12.2
metastatic melanoma 4	21.2	Kidney cancer 3	18.6
metastatic melanoma 5	31.6	Kidney NAT 3	4.6
Bladder cancer 1	2.9	Kidney cancer 4	12.7
Bladder cancer NAT 1	0.0	Kidney NAT 4	4.9
Bladder cancer 2	4.3

[0807] AI_comprehensive panel_v1.0 Summary: Ag5907 Highest expression of this gene is detected in matched control sample for ulcerative colitis (CT=29.5). This gene shows ubiquitous expression in this panel, with moderate to low expression seen 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.

[0808] General_screening_panel v1.5 Summary: Ag5907 Highest expression of this gene is detected in colon cancer HCT-116 cell line (CT=27.4). Moderate to high 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.

[0809] 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.

[0810] 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.

[0811] Interestingly, this gene is expressed at much higher levels in fetal (CT=29.9) when compared to adult liver (CT=33.9). 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.

[0812] Panel 4.1D Summary: Ag5907 Highest expression of this gene is detected in ionomycin treated Ramos B cells (CT=29). This gene shows a wide spread expression in this panel, with moderate to low expression 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 thymus and kidney. Interestingly, expression of this gene is upregulated upon activation of polarized T cells and Ramos B cells. 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.

[0813] Panel 5D Summary: Ag5907 Highest expression of this gene is detected in liver cancer HepG2 cell line (CT=31.3). This gene shows a wide spread expression in this panel, with moderate to low expression in adipose, skeletal muscle, uterus, placenta, heart stromal cells, small intestine and kidney. Please see panel 1.5 for further discussion on the utility of this gene.

[0814] general oncology screening panel_v—2.4 Summary: Ag5907 Highest expression of this gene is detected in kidney cancer (CT=28.2). Moderate to low expression of this gene is detected in normal and cancer samples derived from kidney, colon, lung, prostate, and melanoma. Expression of this gene is consistently higher in cancer samples as compared to adjacent normal tissue. Therefore, expression of this gene may be used as diagnostic marker to detect the presence of these cancer and also therapeutic modulation of this gene or its protein product may be useful in the treatment of melanoma, kidney, colon, lung, and prostate cancers.

[0815] R. CG163259-01: Splice Variant of Cytokine-Like Factor-1-Like Protein.

[0816] Expression of gene CG163259-01 was assessed using the primer-probe set Ag5863, described in Table RA. Results of the RTQ-PCR runs are shown in Table RB.

TABLE RA
Probe Name Ag5863
			Start	Seq ID
Primers		Length	Position	No
Forward	5′-gaggagtaccacggcgagag-3′	20	671	236
Probe	TET-5′-ctgccagataagctgtaggggctcagg-3′-TAMRA	27	694	237
Reverse	5′-cctgaagtgagggtacagaggt-3′	22	771	238

[0817]

TABLE RB
General screening_panel_v1.5
	Rel.		Rel.
	Exp.(%)		Exp.(%)
	Ag5863,		Ag5863,
	Run		Run
Tissue Name	246285252	Tissue Name	246285252
Adipose	0.0	Renal ca. TK-10	27.0
Melanoma* Hs688(A).T	14.1	Bladder	0.1
Melanoma* Hs688(B).T	20.6	Gastric ca. (liver met.) NCI-N87	0.0
Melanoma* M14	0.3	Gastric ca. KATO III	0.2
Melanoma* LOXIMVI	0.0	Colon ca. SW-948	0.0
Melanoma* SK-MEL-5	0.2	Colon ca. SW480	0.4
Squamous cell carcinoma SCC-4	0.0	Colon ca.* (SW480 met) SW620	0.0
Testis Pool	0.5	Colon ca. HT29	0.0
Prostate ca.* (bone met) PC-3	0.0	Colon ca. HCT-116	4.9
Prostate Pool	0.0	Colon ca. CaCo-2	0.0
Placenta	0.2	Colon cancer tissue	0.7
Uterus Pool	0.0	Colon ca. SW1116	0.3
Ovarian ca. OVCAR-3	0.4	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	1.9	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	0.0	Colon Pool	0.3
Ovarian ca. OVCAR-5	2.7	Small Intestine Pool	0.0
Ovarian ca. IGROV-1	1.2	Stomach Pool	0.2
Ovarian ca. OVCAR-8	0.8	Bone Marrow Pool	0.0
Ovary	0.0	Fetal Heart	0.0
Breast ca. MCF-7	2.8	Heart Pool	0.2
Breast ca. MDA-MB-231	0.0	Lymph Node Pool	0.3
Breast ca. BT 549	0.1	Fetal Skeletal Muscle	0.0
Breast ca. T47D	0.8	Skeletal Muscle Pool	1.3
Breast ca. MDA-N	0.0	Spleen Pool	0.3
Breast Pool	0.2	Thymus Pool	0.1
Trachea	1.1	CNS cancer (glio/astro) U87-MG	0.0
Lung	0.0	CNS cancer (glio/astro) U-118-MG	8.9
Fetal Lung	0.2	CNS cancer (neuro; met) SK-N-AS	0.0
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-539	1.9
Lung ca. LX-1	0.0	CNS cancer (astro) SNB-75	0.0
Lung ca. NCI-H146	0.1	CNS cancer (glio) SNB-19	2.0
Lung ca. SHP-77	0.2	CNS cancer (glio) SF-295	2.7
Lung ca. A549	0.3	Brain (Amygdala) Pool	0.4
Lung ca. NCI-H526	0.0	Brain (cerebellum)	0.3
Lung ca. NCI-H23	0.5	Brain (fetal)	0.0
Lung ca. NCI-H460	5.3	Brain (Hippocampus) Pool	0.5
Lung ca. HOP-62	0.2	Cerebral Cortex Pool	2.1
Lung ca. NCI-H522	1.6	Brain (Substantia nigra) Pool	2.4
Liver	0.0	Brain (Thalamus) Pool	0.4
Fetal Liver	0.0	Brain (whole)	0.9
Liver ca. HepG2	100.0	Spinal Cord Pool	0.3
Kidney Pool	0.0	Adrenal Gland	0.5
Fetal Kidney	0.0	Pituitary gland Pool	0.3
Renal ca. 786-0	0.0	Salivary Gland	0.5
Renal ca. A498	1.0	Thyroid (female)	1.1
Renal ca. ACHN	0.0	Pancreatic ca. CAPAN2	0.4
Renal ca. UO-31	0.0	Pancreas Pool	0.4

[0818] General_screening_panel_v1.5 Summary: Ag5863 Highest expression of this gene is detected in liver cancer HepG2 cell line (CT=29.8). Moderate to low levels of expression of this gene is mainly seen in a brain cancer U-118-MG cell line, colon cancer HCT-116 cell line, lung cancer NCI-H460 cell line, renal cancer TK-10 cell line, and two melanoma cell lines. Therefore, expression of this gene may be used as diagnostic marker to detect the presence of melanoma, brain, colon, lung and renal cancers. Furthermore, therapeutic modulation of this gene or its protein product through the use of antibodies or small molecule drug may be useful in the treatment of melanoma, brain, colon, lung and renal cancers.

[0819] S. CG163259-02: Splice Variant of Cytokine-Like Factor-1-Like Protein.

[0820] Expression of gene CG163259-02 was assessed using the primer-probe set Ag5917, described in Table SA. Results of the RTQ-PCR runs are shown in Table SB.

TABLE SA
Probe Name Ag5917
			Start	Seq ID
Primers		Length	Position	No
Forward	5′-gcagcatcctggctctctt-3′	119	480	239
Probe	TET-5′-cgatqtactcacgctggatatcctggatg-3′-TAMRA	29	553	240
Reverse	5′-ggatctggtatttggcttga-3′	20	691	241

[0821]

TABLE SB
General_screening_panel_v1.5
	Rel.		Rel.
	Exp.(%)		Exp.(%)
	Ag5917,		Ag5917,
	Run		Run
Tissue Name	247834853	Tissue Name	247834853
Adipose	0.0	Renal ca. TK-10	13.3
Melanoma* Hs688(A).T	57.4	Bladder	0.0
Melanoma* Hs688(B).T	100.0	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	0.0
Ovarian ca. OVCAR-8	0.0	Bone Marrow Pool	0.0
Ovary	0.0	Fetal Heart	0.0
Breast ca. MCF-7	0.0	Heart Pool	0.0
Breast ca. MDA-MB-231	0.0	Lymph Node Pool	0.0
Breast ca. BT 549	0.0	Fetal Skeletal Muscle	0.0
Breast ca. T47D	0.0	Skeletal Muscle Pool	0.0
Breast ca. MDA-N	0.0	Spleen Pool	0.0
Breast Pool	0.0	Thymus Pool	0.0
Trachea	0.0	CNS cancer (glio/astro) U87-MG	0.0
Lung	0.0	CNS cancer (gilo/astro) U-118-MG	13.6
Fetal Lung	0.0	CNS cancer (neuro; met) SK-N-AS	0.0
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-539	5.1
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	0.0
Lung ca. NCI-H526	0.0	Brain (cerebellum)	0.0
Lung ca. NCI-H23	0.0	Brain (fetal)	0.0
Lung ca. NCI-H460	0.0	Brain (Hippocampus) Pool	0.0
Lung ca. HOP-62	0.0	Cerebral Cortex Pool	0.0
Lung ca. NCI-H522	0.0	Brain (Substantia nigra) Pool	0.0
Liver	0.0	Brain (Thalamus) Pool	0.0
Fetal Liver	0.0	Brain (whole)	0.0
Liver ca. HepG2	82.4	Spinal Cord Pool	0.0
Kidney Pool	0.0	Adrenal Gland	0.0
Fetal Kidney	0.0	Pituitary gland Pool	0.0
Renal ca. 786-0	0.0	Salivary Gland	0.0
Renal ca. A498	2.3	Thyroid (female)	0.0
Renal ca. ACHN	0.0	Pancreatic ca. CAPAN2	0.0
Renal ca. UO-31	0.0	Pancreas Pool	0.0

[0822] General_screening_panel_v1.5 Summary: Ag5917 Low expression of this gene is seen exclusively in a melanoma and a liver cancer cell line samples (CT=34.4-34.7). Therefore, expression of this gene may be used as diagnostic marker to detect the presence of these cancers and also, therapeutic modulation of this gene may be useful in the treatment of these cancers.

[0823] T. CG163259-03: Splice Variant of Cytokine-Like Factor-1-Like Protein.

[0824] Expression of gene CG163259-03 was assessed using the primer-probe set Ag5921, described in Table TA.

TABLE TA
Probe Name Ag5921
			Start	SEQ ID
Primers	Sequenes	Length	Position	No
Forward	5′-gggacaacctcgggcagac-3′	19	450	242
Probe	TET-5′-agcccctacagcttatctggcaggacctct-3′-TAMRA	30	480	243
Reverse	5′-ggtgccctgaagtgagggta-3′	20	571	244

[0825] U. CG163425-01: Interleukin-15 Receptor Alpha Chain Precursor-Like Protein.

[0826] Expression of gene CG163425-01 was assessed using the primer-probe set Ag5904, described in Table UA. Results of the RTQ-PCR runs are shown in Tables UB, UC and UD.

TABLE UA
Probe Name Ag5904
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-caaatgcattagaaccacagaga-3′	23	355	245
Probe	TET-5′-taagcagtcatgagtcctcccacgg-3′-TAMRA	25	378	246
Reverse	5′-agttcttggctgttgtctgaga-3′	22	410	247

[0827]

TABLE UB
AI_comprehensive panel_v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag5904,		Ag5904,
	Run		Run
Tissue Name	247947768	Tissue Name	247947768
110967 COPD-F	11.6	112427 Match Control Psoriasis-F	66.4
110980 COPD-F	27.4	112418 Psoriasis-M	6.0
110968 COPD-M	31.4	112723 Match Control Psoriasis-M	0.0
110977 COPD-M	100.0	112419 Psoriasis-M	7.6
110989 Emphysema-F	27.5	112424 Match Control Psoriasis-M	4.0
110992 Emphysema-F	10.1	112420 Psoriasis-M	60.7
110993 Emphysema-F	5.0	112425 Match Control Psoriasis-M	49.7
110994 Emphysema-F	0.0	104689 (MF) OA Bone-Backus	5.8
110995 Emphysema-F	15.9	104690 (MF) Adj “Normal”	0.0
		Bone-Backus
110996 Emphysema-F	4.0	104691 (MF) OA Synovium-Backus	0.0
110997 Asthma-M	2.3	104692 (BA) OA Cartilage-Backus	9.5
111001 Asthma-F	11.3	104694 (BA) OA Bone-Backus	11.0
111002 Asthma-F	20.7	104695 (BA) Adj “Normal”	14.3
		Bone-Backus
111003 Atopic Asthma-F	17.6	104696 (BA) OA Synovium-Backus	19.9
111004 Atopic Asthma-F	16.4	104700 (SS) OA Bone-Backus	21.8
111005 Atopic Asthma-F	5.1	104701 (SS) Adj “Normal”	3.4
		Bone-Backus
111006 Atopic Asthma-F	7.7	104702 (SS) OA Synovium-Backus	18.2
111417 Allergy-M	5.8	117093 OA Cartilage Rep7	18.0
112347 Allergy-M	0.0	112672 OA Bone5	28.9
112349 Normal Lung-F	0.0	112673 OA Synovium5	24.0
112357 Normal Lung-F	15.4	112674 OA Synovial Fluid cells5	4.6
112354 Normal Lung-M	0.0	117100 OA Cartilage Rep14	18.6
112374 Crohns-F	20.7	112756 OA Bone9	0.0
112389 Match Control Crohns-F	2.7	112757 OA Synovium9	5.8
112375 Crohns-F	24.7	112758 OA Synovial Fluid Cells9	10.3
112732 Match Control Crohns-F	18.7	117125 RA Cartilage Rep2	18.6
112725 Crohns-M	0.0	113492 Bone2 RA	12.6
112387 Match Control	8.2	113493 Synovium2 RA	7.6
Crohns-M
112378 Crohns-M	0.0	113494 Syn Fluid Cells RA	3.2
112390 Match Control	11.6	113499 Cartilage4 RA	12.8
Crohns-M
112726 Crohns-M	43.2	113500 Bone4 RA	14.4
112731 Match Control	14.8	113501 Synovium4 RA	35.6
Crohns-M
112380 Ulcer Col-F	8.8	113502 Syn Fluid Cells4 RA	8.5
112734 Match Control Ulcer	13.9	113495 Cartilage3 RA	6.6
Col-F
112384 Ulcer Col-F	53.2	113496 Bone3 RA	14.7
112737 Match Control Ulcer	9.0	113497 Synovium3 RA	3.1
Col-F
112386 Ulcer Col-F	0.0	113498 Syn Fluid Cells3 RA	25.2
112738 Match Control Ulcer	17.8	117106 Normal Cartilage Rep20	8.6
Col-F
112381 Ulcer Col-M	0.0	113663 Bone3 Normal	4.1
112735 Match Control Ulcer	12.9	113664 Synovium3 Normal	0.0
Col-M
112382 Ulcer Col-M	10.8	113665 Syn Fluid Cells3 Normal	0.0
112394 Match Control Ulcer	3.8	117107 Normal Cartilage Rep22	28.7
Col-M
112383 Ulcer Col-M	65.1	113667 Bone4 Normal	15.9
112736 Match Control Ulcer	0.0	113668 Synovium4 Normal	15.5
Col-M
112423 Psoriasis-F	3.7	113669 Syn Fluid Cells4 Normal	22.7

[0828]

TABLE UC
General_screening_panel_v1.5
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag5904,		Ag5904,
	Run		Run
Tissue Name	247946847	Tissue Name	247946847
Adipose	2.8	Renal ca. TK-10	8.5
Melanoma* Hs688(A).T	3.5	Bladder	12.1
Melanoma* Hs688(B).T	1.2	Gastric ca. (liver met.) NCI-N87	100.0
Melanoma* M14	0.0	Gastric ca. KATO III	21.0
Melanoma* LOXIMVI	4.2	Colon ca. SW-948	6.2
Melanoma* SK-MEL-5	0.0	Colon ca. SW480	28.7
Squamous cell carcinoma SSC-4	7.6	Colon ca.* (SW480 met) SW620	0.8
Testis Pool	3.0	Colon ca. HT29	2.7
Prostate ca.* (bone met) PC-3	2.7	Colon ca. HCT-116	9.8
Prostate Pool	2.1	Colon ca. CaCo-2	0.0
Placenta	3.5	Colon cancer tissue	19.8
Uterus Pool	1.2	Colon ca. SW1116	4.3
Ovarian ca. OVCAR-3	4.6	Colon ca. Colo-205	2.3
Ovarian ca. SK-OV-3	55.9	Colon ca. SW-48	0.4
Ovarian ca. OVCAR-4	5.0	Colon Pool	2.2
Ovarian ca. OVCAR-5	72.2	Small Intestine Pool	11.6
Ovarian ca. IGROV-1	8.9	Stomach Pool	2.7
Ovarian ca. OVCAR-8	4.1	Bone Marrow Pool	2.3
Ovary	1.2	Fetal Heart	0.0
Breast ca. MCF-7	2.2	Heart Pool	1.3
Breast ca. MDA-MB-231	25.9	Lymph Node Pool	6.5
Breast ca. BT 549	3.8	Fetal Skeletal Muscle	0.7
Breast ca. T47D	1.5	Skeletal Muscle Pool	12.0
Breast ca. MDA-N	0.3	Spleen Pool	16.8
Breast Pool	8.1	Thymus Pool	2.6
Trachea	9.5	CNS cancer (glio/astro) U87-MG	12.2
Lung	0.3	CNS cancer (glio/astro) U-118-MG	8.2
Fetal Lung	18.2	CNS cancer (neuro; met) SK-N-AS	7.6
Lung ca. NCI-N417	0.0	CNS cancer (astro) SF-539	3.8
Lung ca. LX-1	5.0	CNS cancer (astro) SNB-75	8.6
Lung ca. NCI-H146	0.0	CNS cancer (glio) SNB-19	0.8
Lung ca. SHP-77	0.0	CNS cancer (glio) SF-295	60.3
Lung ca. A549	0.0	Brain (Amygdala) Pool	0.7
Lung ca. NCI-H526	0.0	Brain (cerebellum)	0.8
Lung ca. NCI-H23	5.1	Brain (fetal)	0.0
Lung ca. NCI-H460	4.4	Brain (Hippocampus) Pool	0.0
Lung ca. HOP-62	4.4	Cerebral Cortex Pool	3.3
Lung ca. NCI-H522	4.7	Brain (Substantia nigra) Pool	0.0
Liver	1.8	Brain (Thalamus) Pool	0.0
Fetal Liver	8.5	Brain (whole)	3.1
Liver ca. HepG2	0.0	Spinal Cord Pool	2.0
Kidney Pool	16.4	Adrenal Gland	5.5
Fetal Kidney	0.0	Pituitary gland Pool	0.0
Renal ca. 786-0	2.8	Salivary Gland	1.8
Renal ca. A498	10.1	Thyroid (female)	0.0
Renal ca. ACHN	0.0	Pancreatic ca. CAPAN2	33.2
Renal ca. UO-31	8.1	Pancreas Pool	13.9

[0829]

TABLE UD
Panel 4.1D
	Rel.		Rel.
	Exp. ()		Exp. (%)
	Ag5904,		Ag5904,
	Run		Run
Tissue Name	247574996	Tissue Name	247574996
Secondary Th1 act	25.9	HUVEC IL-1beta	22.5
Secondary Th2 act	47.6	HUVEC IFN gamma	34.4
Secondary Tr1 act	5.2	HUVEC TNF alpha + IFN gamma	15.9
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	5.0
Secondary Th2 rest	0.0	HUVEC IL-11	5.2
Secondary Tr1 rest	0.0	Lung Microvascular EC none	8.5
Primary Th1 act	0.0	Lung Microvascular EC TNF alpha +	6.1
		IL-1beta
Primary Th2 act	12.2	Microvascular Dermal EC none	1.8
Primary Tr1 act	14.1	Microsvasular Dermal EC	17.1
		TNF alpha + IL-1beta
Primary Th1 rest	0.0	Bronchial epithelium TNF alpha +	0.0
		IL1beta
Primary Th2 rest	0.0	Small airway epithelium none	3.0
Primary Tr1 rest	0.0	Small airway epithelium TNF alpha +	4.0
		IL-1beta
CD45RA CD4 lymphocyte act	29.5	Coronery artery SMC rest	1.6
CD45RO CD4 lymphocyte act	11.2	Coronery artery SMC TNF alpha +	11.1
		IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	0.0
Secondary CD8 lymphocyte rest	11.5	Astrocytes TNF alpha + IL-1beta	0.0
Secondary CD8 lymphocyte act	0.9	KU-812 (Basophil) rest	4.0
CD4 lymphocyte none	0.0	KU-812 (Basophil)	7.5
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	0.0	CCD1106 (Keratinocytes) none	1.7
CH11
LAK cells rest	10.2	CCD1106 (Keratinocytes)	15.9
		TNF alpha + IL-1beta
LAK cells IL-2	1.6	Liver cirrhosis	3.3
LAK cells IL-2 + IL-12	7.3	NCI-H292 none	1.6
LAK cells IL-2 + IFN gamma	1.7	NCI-H292 IL-4	8.0
LAK cells IL-2 + IL-18	1.6	NCI-H292 IL-9	9.8
LAK cells PMA/ionomycin	29.7	NCI-H292 IL-13	9.2
NK Cells IL-2 rest	9.2	NCI-H292 IFN gamma	2.9
Two Way MLR 3 day	10.7	HPAEC none	6.0
Two Way MLR 5 day	0.7	HPAEC TNF alpha + IL-1beta	76.8
Two Way MLR 7 day	0.6	Lung fibroblast none	9.5
PBMC rest	0.0	Lung fibroblast TNF alpha + IL-	42.3
		1beta
PBMC PWM	8.0	Lung fibroblast IL-4	0.0
PBMC PHA-L	4.7	Lung fibroblast IL-9	1.3
Ramos (B cell) none	0.0	Lung fibroblast IL-13	0.0
Ramos (B cell) ionomycin	4.5	Lung fibroblast IFN gamma	54.7
B lymphocytes PWM	14.6	Dermal fibroblast CCD1070 rest	1.5
B lymphocytes CD40L and IL-4	9.0	Dermal fibroblast CCD1070 TNF	12.1
		alpha
EOL-1 dbcAMP	0.5	Dermal fibroblast CCD1070 IL-	0.0
		1beta
EOL-1 dbcAMP	0.0	Dermal fibroblast IFN gamma	35.8
PMA/ionomycin
Dendritic cells none	3.4	Dermal fibroblast IL-4	22.4
Dendritic cells LPS	1.8	Dermal Fibroblasts rest	2.7
Dendritic cells anti-CD40	0.0	Neutrophils TNFa + LPS	0.0
Monocytes rest	0.0	Neutrophils rest	0.0
Monocytes LPS	100.0	Colon	0.0
Macrophages rest	0.0	Lung	0.0
Macrophages LPS	26.6	Thymus	0.0
HUVEC none	1.6	Kidney	3.0
HUVEC starved	2.9

[0830] AI_comprehensive panel_v1.0 Summary: Ag5904 Detectable expression is limited to a COPD sample (CT=34.4).

[0831] General_screening_panel_v1.5 Summary: Ag5904 Highest expression is seen in a gastric cancer cell line (CT=31.7). Moderate to low levels of expression are also seen in cell lines derived from breast cancer, ovarian cancer, pancreatic cancer, and brain cancer. 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.

[0832] Panel 4.1D Summary: Ag5904 Highest expression is seen in LPS treated monocytes (CT=32.4). Low but significant levels are also seen in IFN gamma treated lung and dermal fibroblasts, TNF-a/IL1-b treated HPAECs and lung fibroblasts, LPS treated macrophages, chronically activated Th1 and Th2 cells, and PMA/ionomycin treated LAK cells.

[0833] Upon activation with pathogens such as LPS, 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 transcript may prevent the recruitment of monocytes and the initiation of the inflammatory process, and reduce the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, or rheumatoid arthritis.

[0834] V. CG163957-01: D86-Like Protein.

[0835] Expression of gene CG163957-01 was assessed using the primer-probe sets Ag5873 and Ag7796, described in Tables VA and VB. Results of the RTQ-PCR runs are shown in Tables VC and VD.

TABLE VA
Probe Name Ag5873
			Start	SEQ ID
Primers	Sequenes	Length	Position	No
Forward	5′-aggtgaaccttgtgatattttgaa-3′	24	981	248
Probe	TET-5′-cagaaaatagtatatgttgcaagacacccc-3′-TAMRA	30	1010	249
Reverse	5′-gatatacagttttgagaatatgaggtttg-3′	29	1041	250

[0836]

TABLE VB
Probe Name Ag7796
			Start	SEQ ID
Primers		Length	Position	No
Forward	5′-aatgaatttgataggcgatttg-3′	22	5005	251
Probe	TET-5′-ccaaacattgacctggtgttgcca-3′-TAMRA	24	5035	252
Reverse	5′-cttgtcattcctgtagttgatcct-3′	24	5064	253

[0837]

TABLE VC
CNS_neurodegeneration_v1.0
	Rel.	Rel.		Rel.	Rel.
	Exp. (%)	Exp. (%)		Exp. (%)	Exp. (%)
	Ag5873,	Ag7796,		Ag5873,	Ag7796,
	Run	Run		Run	Run
Tissue Name	247854047	312372410	issue Name	247854047	312372410
AD 1 Hippo	0.0	11.7	Control (Path) 3	39.2	2.2
			Temporal Ctx
AD 2 Hippo	31.6	0.0	Control (Path) 4	41.8	4.1
			Temporal Ctx
AD 3 Hippo	72.2	0.5	AD 1 Occipital Ctx	0.0	6.9
AD 4 Hippo	0.0	0.0	AD 2 Occipital Ctx	0.0	0.0
			(Missing)
AD 5 Hippo	46.3	0.0	AD 3 Occipital Ctx	0.0	4.3
AD 6 Hippo	24.3	100.0	AD 4 Occipital Ctx	16.0	0.0
Control 2 Hippo	0.0	7.2	AD 5 Occipital Ctx	19.5	4.7
Control 4 Hippo	26.2	0.0	AD 6 Occipital Ctx	41.5	13.4
Control (Path) 3	100.0	25.0	Control 1 Occipital	0.0	10.5
Hippo			Ctx
AD 1 Temporal Ctx	92.7	6.0	Control 2 Occipital	18.3	2.2
			Ctx
AD 2 Temporal Ctx	47.0	3.3	Control 3 Occipital	19.9	0.0
			Ctx
AD 3 Temporal Ctx	16.6	8.9	Control 4 Occipital	36.9	4.9
			Ctx
AD 4 Temporal Ctx	0.0	1.4	Control (Path) 1	18.6	11.7
			Occipital Ctx
AD 5 Inf Temporal	16.0	0.7	Control (Path) 2	42.9	8.2
Ctx			Occipital Ctx
AD 5 Sup Temporal	80.1	0.0	Control (Path) 3	20.7	2.2
Ctx			Occipital Ctx
AD 6 Inf Temporal	48.6	2.0	Control (Path) 4	20.4	13.1
Ctx			Occipital Ctx
AD 6 Sup Temporal	31.2	14.2	Control 1 Parietal	57.4	4.4
Ctx			Ctx
Control 1 Temporal	18.2	3.8	Control 2 Parietal	22.5	0.0
Ctx			Ctx
Control 2 Temporal	11.0	1.7	Control 3 Parietal	0.0	0.0
Ctx			Ctx
Control 3 Temporal	43.2	2.6	Control (Path) 1	0.0	0.0
Ctx			Parietal Ctx
Control 3 Temporal	0.0	0.0	Control (Path) 2	93.3	7.7
Ctx			Parietal Ctx
Control (Path) 1	20.3	0.0	Control (Path) 3	0.0	2.0
Temporal Ctx			Parietal Ctx
Control (Path) 2	91.4	2.4	Control (Path) 4	59.5	5.9
Temporal Ctx			Parietal Ctx

[0838]

TABLE VD
Panel 4.1D
	Rel.	Rel.		Rel.	Rel.
	Exp. (%)	Exp. (%)		Exp. (%)	Exp. (%)
	Ag5873,	Ag7796,		Ag5873,	Ag7796,
	Run	Run		Run	Run
Tissue Name	247850137	312355982	Tissue Name	247850137	312355982
Secondary Th1 act	0.0	0.0	HUVEC IL-1beta	1.0	0.0
Secondary Th2 act	0.0	0.0	HUVEC IFN gamma	6.3	2.7
Secondary Tr1 act	0.0	0.0	HUVEC TNF alpha +	0.0	1.0
			IFN gamma
Secondary Th1 rest	0.0	0.0	HUVEC TNF alpha +	0.0	0.0
			IL4
Secondary Th2 rest	0.0	0.0	HUVEC IL-11	4.2	0.8
Secondary Tr1 rest	0.0	0.0	Lung Microvascular	100.0	47.6
			EC none
Primary Th1 act	0.0	0.0	Lung Microvascular	18.3	7.4
			EC TNF alpha +
			IL-1beta
Primary Th2 act	0.0	0.0	Microvascular	3.6	1.5
			Dermal EC none
Primary Tr1 act	0.0	0.0	Microvasular	5.5	1.6
			Dermal EC TNF
			alpha + IL-1beta
Primary Th1 rest	0.0	0.0	Bronchial epithelium	0.0	0.0
			TNF alpha + IL1beta
Primary Th2 rest	0.0	0.0	Small airway	0.0	0.0
			epithelium none
Primary Tr1 rest	0.0	0.0	Small airway	0.0	0.0
			epithelium TNF
			alpha + IL-1beta
CD45RA CD4	0.0	0.0	Coronery artery SMC	0.0	0.0
lymphocyte act			rest
CD45RO CD4	0.0	0.0	Coronery artery SMC	0.0	0.0
lymphocyte act			TNF alpha + IL-1beta
CD8 lymphocyte act	0.0	0.0	Astrocytes rest	0.0	0.0
Secondary CD8	0.0	0.0	Astrocytes TNF	0.0	0.0
lymphocyte rest			alpha + IL-1beta
Secondary CD8	0.0	0.0	KU-812 (Basophil)	0.0	0.0
lymphocyte act			rest
CD4 lymphocyte none	0.0	100.0	KU-812 (Basophil)	3.8	1.7
			PMA/ionomycin
2ry	0.0	0.0	CCD1106	0.5	0.0
Th1/Th2/Tr1_anti-CD95			(Keratinocytes) none
CH11
LAK cells rest	0.0	0.0	CCD1106	0.0	0.0
			(Keratinocytes)
			TNF alpha + IL-1beta
LAK cells IL-2	0.0	0.0	Liver cirrhosis	8.4	3.8
LAK cells IL-2 + IL-12	0.0	0.0	NCI-H292 none	0.0	0.0
LAK cells IL-2 + IFN	0.0	0.0	NCI-H292 IL-4	0.0	0.0
gamma
LAK cells IL-2 + IL-18	0.0	0.0	NCI-H292 IL-9	0.0	0.0
LAK cells	0.0	0.0	NCI-H292 IL-13	0.0	0.0
PMA/ionomycin
NK Cells IL-2 rest	0.0	0.0	NCI-H292 IFN	0.0	0.0
			gamma
Two Way MLR 3 day	0.0	0.0	HPAEC none	9.2	3.0
Two Way MLR 5 day	0.0	0.0	HPAEC TNF alpha +	2.7	1.3
			IL-1beta
Two Way MLR 7 day	0.0	0.0	Lung fibroblast none	0.8	0.0
PBMC rest	0.0	0.2	Lung fibroblast TNF	0.0	0.0
			alpha + IL-1beta
PBMC PWM	0.0	0.0	Lung fibroblast IL-4	0.0	0.0
PBMC PHA-L	0.0	0.0	Lung fibroblast IL-9	0.0	0.0
Ramos (B cell) none	0.0	0.0	Lung fibroblast IL-13	0.0	0.0
Ramos (B cell)	0.0	0.0	Lung fibroblast IFN	0.0	0.0
ionomycin			gamma
B lymphocytes PWM	0.0	0.0	Dermal fibroblast	0.0	0.0
			CCD1070 rest
B lymphocytes CD40L	0.0	0.0	Dermal fibroblast	0.0	0.0
and IL-4			CCD1070 TNF alpha
EOL-1 dbcAMP	0.0	0.0	Dermal fibroblast	0.0	0.0
			CCD1070 IL-1beta
EOL-1 dbcAMP	0.0	0.0	Dermal fibroblast	0.0	0.0
PMA/ionomycin			IFN gamma
Dendritic cells none	0.0	0.0	Dermal fibroblast	0.0	0.0
			IL-4
Dendritic cells LPS	0.0	0.0	Dermal Fibroblasts	0.0	0.0
			rest
Dendritic cells	0.0	0.0	Neutrophils	0.0	0.0
anti-CD40			TNFa + LPS
Monocytes rest	0.0	0.0	Neutrophils rest	0.0	0.0
Monocytes LPS	0.0	0.0	Colon	0.0	0.6
Macrophages rest	0.0	0.0	Lung	1.2	0.3
Macrophages LPS	0.0	0.0	Thymus	0.0	0.0
HUVEC none	1.6	0.0	Kidney	2.2	0.6
HUVEC starved	0.0	0.0

[0839] CNS_neurodegeneration_v1.0 Summary: Ag5873/Ag7796 Two experiments with two different probe and primer sets show that this gene is not differentially expressed in Alzheimer's disease. However, this profile does show that this gene is expressed 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.

[0840] Panel 4.1D Summary: Ag5873 Highest expression of this gene is seen in untreated lung microvascular endothelial cells (CT=29). Lower levels of expression are seen in these cells treated with TNF-a/IL-1b. Endothelial cells are known to play important roles in inflammatory responses by altering the expression of surface proteins that are involved in activation and recruitment of effector inflammatory cells. This expression suggests a role for this gene in the maintenance of the integrity of the microvasculature. Therefore, therapeutics designed for this putative protein could be beneficial for the treatment of diseases associated with damaged microvasculature including heart diseases or inflammatory diseases, such as psoriasis, asthma, and chronic obstructive pulmonary diseases.

[0841] In addition, this expression in lung microvascular endothelial cells suggests that the protein encoded by this transcript may also be involved in lung disorders including asthma, allergies, chronic obstructive pulmonary disease, and emphysema. Therefore, therapeutic modulation of the protein encoded by this gene may lead to amelioration of symptoms associated with psoriasis, asthma, allergies, chronic obstructive pulmonary disease, and emphysema.

[0842] A related murine cDNA (AccNo AB055648.1) was found to be 83% identical at the protein level and the protein encoded by this cDNA was identified as a lymphocyte secretion product. The difference between tissues that express the murine and human protein suggest that D86 protein encoded by this gene, as well as the murine protein, may be involved in selective processes in the immune response and thus be suitable targets for therapeutic intervention at these sites.

[0843] W. CG164482-01: 4930418P06RIK Homolog with Rhomboid Domain-Like Protein.

[0844] Expression of gene CG164482-01 was assessed using the primer-probe sets Ag776, Ag6089 and Ag6090, described in Tables WA, WB and WC. Results of the RTQ-PCR runs are shown in Tables WD, WE, WF and WG.

TABLE WA
Probe Name Ag776
			Start	SEQ ID
Primers	Sequence	Length	Position	No
Forward	5′-aacggagatcaagagggataaa-3′	22	105	254
Probe	TET-5′-tcctttctcaaatcttccatgttggga-3′-TAMRA	27	144	255
Reverse	5′-tagggtgacaggtggaatattg-3′	22	175	256

[0845]

TABLE WB
Probe Name Ag6089
			Start	SEQ ID
Primers	Sequencs	Length	Position	No
Forward	5′-aataaatctagaaagaagactgggaagtag-3′	30	376	257
Probe	TET-5′-atggtttgcctatgttatcaccgcat-3′-TAMRA	26	406	258
Reverse	5′-aggtataccactccagtaagtacagaaa-3′	28	432	259

[0846]

TABLE WC
Probe Name Ag6090
			Start	SEQ ID
Primers	Sequencs	Length	Position	No
Forward	5′-aataaatctagaaagaagactgggaagtag-3′	30	376	260
Probe	TET-5′-atggtttgcctatgttatcaccgcat-3′-TAMRA	26	406	261
Reverse	5′-aggtataccactccagtaagtacagaaa-3′	28	432	262

[0847]

TABLE WD
CNS_neurodegeneration_v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag6090,		Ag6090,
	Run		Run
Tissue Name	248386492	Tissue Name	248386492
AD 1 Hippo	24.0	Control (Path) 3 Temporal Ctx	12.6
AD 2 Hippo	33.2	Control (Path) 4 Temporal Ctx	29.3
AD 3 Hippo	13.6	AD 1 Occipital Ctx	18.0
AD 4 Hippo	7.8	AD 2 Occipital Ctx (Missing)	0.0
AD 5 hippo	67.4	AD 3 Occipital Ctx	11.3
AD 6 Hippo	76.3	AD 4 Occipital Ctx	22.1
Control 2 Hippo	22.4	AD 5 Occipital Ctx	20.6
Control 4 Hippo	14.9	AD 6 Occipital Ctx	37.6
Control (Path) 3 Hippo	21.0	Control 1 Occipital Ctx	10.4
AD 1 Temporal Ctx	28.1	Control 2 Occipital Ctx	47.0
AD 2 Temporal Ctx	38.2	Control 3 Occipital Ctx	20.7
AD 3 Temporal Ctx	10.0	Control 4 Occipital Ctx	14.1
AD 4 Temporal Ctx	25.2	Control (Path) 1 Occipital Ctx	69.7
AD 5 Inf Temporal Ctx	100.0	Control (Path) 2 Occipital Ctx	14.2
AD 5 SupTemporal Ctx	37.1	Control (Path) 3 Occipital Ctx	15.9
AD 6 Inf Temporal Ctx	69.7	Control (Path) 4 Occipital Ctx	15.7
AD 6 Sup Temporal Ctx	67.8	Control 1 Parietal Ctx	12.7
Control 1 Temporal Ctx	13.4	Control 2 Parietal Ctx	59.5
Control 2Temporal Ctx	33.0	Control 3 Parietal Ctx	16.3
Control 3 Temporal Ctx	20.4	Control (Path) 1 Parietal Ctx	44.8
Control 4 Temporal Ctx	13.7	Control (Path) 2 Parietal Ctx	27.5
Control (Path) 1 Temporal Ctx	43.5	Control (Path) 3 Parietal Ctx	13.7
Control (Path) 2 Temporal Ctx	34.4	Control (Path) 4 Parietal Ctx	33.2

[0848]

TABLE WE
General_screening_panel_v1.5
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag6089,		Ag6089,
	Run		Run
Tissue Name	246733787	Tissue Name	246733787
Adipose	16.8	Renal ca. TK-10	27.4
Melanoma* Hs688(A).T	51.8	Bladder	26.6
Melanoma* Hs688(B).T	57.0	Gastric ca. (liver met.) NCI-N87	36.1
Melanoma* M14	26.2	Gastric ca. KATO III	29.1
Melanoma* LOXIMVI	31.6	Colon ca. SW-948	13.9
Melanoma* SK-MEL-5	37.1	Colon ca. SW480	19.6
Squamous cell carcinoma SCC-4	19.6	Colon ca.* (SW480 met) SW620	41.8
Testis Pool	20.4	Colon ca. HT29	11.3
Prostate ca.* (bone met) PC-3	73.7	Colon ca. HCT-116	58.2
Prostate Pool	19.9	Colon ca. CaCo-2	14.2
Placenta	13.6	Colon cancer tissue	20.9
Uterus Pool	31.2	Colon ca. SW1116	3.8
Ovarian ca. OVCAR-3	22.7	Colon ca. Colo-205	4.9
Ovarian ca. SK-OV-3	50.7	Colon ca. SW-48	6.2
Ovarian ca. OVCAR-4	11.3	Colon Pool	29.1
Ovarian ca. OVCAR-5	56.3	Small Intestine Pool	34.9
Ovarian ca. IGROV-1	21.8	Stomach Pool	19.5
Ovarian ca. OVCAR-8	14.9	Bone Marrow Pool	12.4
Ovary	25.0	Fetal Heart	10.2
Breast ca. MCF-7	37.9	Heart Pool	14.0
Breast ca. MDA-MB-231	16.7	Lymph Node Pool	29.7
Breast ca. BT 549	20.7	Fetal Skeletal Muscle	5.6
Breast ca. T47D	7.2	Skeletal Muscle Pool	21.8
Breast ca. MDA-N	4.9	Spleen Pool	21.3
Breast Pool	25.7	Thymus Pool	28.1
Trachea	36.1	CNS cancer (glio/astro) U87-MG	47.6
Lung	5.9	CNS cancer (glio/astro) U-118-MG	27.5
Fetal Lung	36.9	CNS cancer (neuro; met) SK-N-AS	24.5
Lung ca. NCI-N417	6.2	CNS cancer (astro) SF-539	26.1
Lung ca. LX-1	73.2	CNS cancer (astro) SNB-75	36.3
Lung ca. NCI-H146	7.9	CNS cancer (glio) SNB-19	23.0
Lung ca. SHP-77	25.9	CNS cancer (glio) SF-295	100.0
Lung ca. A549	27.7	Brain (Amygdala) Pool	22.4
Lung ca. NCI-H526	4.3	Brain (cerebellum)	77.9
Lung ca. NCI-H23	48.6	Brain (fetal)	21.5
Lung ca. NCI-H460	55.9	Brain (Hippocampus) Pool	24.0
Lung ca. HOP-62	18.7	Cerebral Cortex Pool	19.1
Lung ca. NCI-H522	46.0	Brain (Substantia nigra) Pool	21.6
Liver	4.8	Brain (Thalamus) Pool	28.9
Fetal Liver	50.3	Brain (whole)	25.9
Liver ca. HepG2	0.0	Spinal Cord Pool	23.7
Kidney Pool	54.3	Adrenal Gland	24.0
Fetal Kidney	20.4	Pituitary gland Pool	5.1
Renal ca. 786-0	25.9	Salivary Gland	13.9
Renal ca. A498	9.5	Thyroid (female)	23.3
Renal ca. ACHN	32.1	Pancreatic ca. CAPAN2	28.9
Renal ca. UO-31	18.9	Pancreas Pool	29.1

[0849]

TABLE WF
Panel 1.2
	Rel.		Rel.
	Exp (%)		Exp. (%)
	Ag776,		Ag776,
	Run		Run
Tissue Name	116762332	Tissue Name	116762332
Endothelial cells	23.0	Renal ca. 786-0	9.3
Heart (Fetal)	45.7	Renal ca. A498	25.7
Pancreas	51.8	Renal ca. RXF 393	5.5
Pancreatic ca. CAPAN 2	7.7	Renal ca. ACHN	27.7
Adrenal Gland	30.8	Renal ca. UO-31	8.8
Thyroid	37.1	Renal ca. TK-10	18.7
Salivary gland	26.6	Liver	16.3
Pituitary gland	21.2	Liver (fetal)	24.8
Brain (fetal)	11.3	Liver ca. (hepatoblast) HepG2	0.0
Brain (whole)	21.8	Lung	9.6
Brain (amygdala)	10.5	Lung (fetal)	11.4
Brain (cerebellum)	9.0	Lung ca. (small cell) LX-1	65.5
Brain (hippocampus)	15.6	Lung ca. (small cell) NCI-H69	15.3
Brain (thalamus)	10.5	Lung ca. (s.cell var.) SHP-77	5.8
Cerebral Cortex	67.4	Lung ca. (large cell) NCI-H460	100.0
Spinal cord	14.0	Lung ca. (non-sm. cell) A549	44.4
glio/astro U87-MG	38.2	Lung ca. (non-s.cell) NCI-H23	19.9
glio/astro U-118-MG	6.9	Lung ca. (non-s.cell) HOP-62	30.8
astrocytoma SW1783	6.4	Lung ca. (non-s.cl) NCI-H522	95.9
neuro*; met SK-N-AS	27.9	Lung ca. (squam.) SW 900	12.5
astrocytoma SF-539	9.4	Lung ca. (squam.) NCI-H596	15.8
astrocytoma SNB-75	4.1	Mammary gland	23.2
glioma SNB-19	25.2	Breast ca.* (pl.ef) MCF-7	26.4
glioma U251	10.2	Breast ca.* (pl.ef) MDA-MB-231	8.3
glioma SF-295	0.6	Breast ca.* (pl. ef) T47D	52.1
Heart	28.9	Breast ca. BT-549	8.4
Skeletal Muscle	69.3	Breast ca. MDA-N	6.3
Bone marrow	19.3	Ovary	64.2
Thymus	11.6	Ovarian ca. OVCAR-3	24.7
Spleen	10.9	Ovarian ca. OVCAR-4	16.5
Lymph node	22.1	Ovarian ca. OVCAR-5	57.4
Colorectal Tissue	9.4	Ovarian ca. OVCAR-8	15.6
Stomach	22.2	Ovarian ca. IGROV-1	21.5
Small intestine	26.6	Ovarian ca. (ascites) SK-OV-3	44.8
Colon ca. SW480	2.8	Uterus	11.5
Colon ca.* SW620 (SW480 met)	25.5	Placenta	21.3
Colon ca. HT29	7.5	Prostate	21.8
Colon ca. HCT-116	0.3	Prostate ca.* (bone met) PC-3	61.1
Colon ca. CaCo-2	18.4	Testis	55.9
Colon ca. Tissue (ODO3866)	3.1	Melanoma Hs688(A).T	13.0
Colon ca. HCC-2998	36.6	Melanoma* (met) Hs688(B).T	15.7
Gastric ca.* (liver met) NCI-N87	72.7	Melanoma UACC-62	44.8
Bladder	73.2	Melanoma M14	12.2
Trachea	4.7	Melanoma LOX IMVI	10.4
Kidney	22.1	Melanoma* (met) SK-MEL-5	20.9
Kidney (fetal)	16.8

[0850]

TABLE WG
Panel 4.1D
	Rel.		Rel.
	Exp. ()		Exp. (%)
	Ag6089,		Ag6089,
	Run		Run
Tissue Name	247582904	Tissue Name	247582904
Secondary Th1 act	68.8	HUVEC IL-1beta	28.7
Secondary Th2 act	100.0	HUVEC IFN gamma	32.8
Secondary Tr1 act	17.1	HUVEC TNF alpha + IFN gamma	7.7
Secondary Th1 rest	0.8	HUVEC TNF alpha + IL4	4.0
Secondary Th2 rest	2.7	HUVEC IL-11	16.4
Secondary Tr1 rest	1.1	Lung Microvascular EC none	37.9
Primary Th1 act	1.4	Lung Microvascular EC TNF alpha +	10.7
		IL-1beta
Primary Th2 act	52.5	Microvascular Dermal EC none	6.0
Primary Tr1 act	43.5	Microsvasular Dermal EC	9.2
		TNF alpha + IL-1beta
Primary Th1 rest	0.9	Bronchial epithelium TNF alpha +	37.9
		IL1beta
Primary Th2 rest	2.3	Small airway epithelium none	22.7
Primary Tr1 rest	1.6	Small airway epithelium TNF alpha +	43.8
		IL-1beta
CD45RA CD4 lymphocyte act	52.1	Coronery artery SMC rest	21.0
CD45RO CD4 lymphocyte act	61.6	Coronery artery SMC TNF alpha +	27.9
		IL-1beta
CD8 lymphocyte act	5.3	Astrocytes rest	5.3
Secondary CD8 lymphocyte rest	22.7	Astrocytes TNF alpha + IL-1beta	6.6
Secondary CD8 lymphocyte act	6.3	KU-812 (Basophil) rest	30.1
CD4 lymphocyte none	2.6	KU-812 (Basophil)	49.3
		PMA/ionomycin
2ry Th1/Th2/Tr1_anti-CD95	2.9	CCD1106 (Keratinocytes) none	40.6
CH11
LAK cells rest	27.5	CCD1106 (Keratinocytes)	26.1
		TNF alpha + IL-1beta
LAK cells IL-2	13.3	Liver cirrhosis	13.2
LAK cells IL-2 + IL-12	4.0	NCI-H292 none	27.9
LAK cells IL-2 + IFN gamma	14.8	NCI-H292 IL-4	25.9
LAK cells IL-2 + IL-18	9.7	NCI-H292 IL-9	37.6
LAK cells PMA/ionomycin	79.0	NCI-H292 IL-13	39.8
NK Cells IL-2 rest	67.8	NCI-H292 IFN gamma	24.8
Two Way MLR 3 day	20.6	HPAEC none	5.2
Two Way MLR 5 day	1.1	HPAEC TNF alpha + IL-1beta	40.3
Two Way MLR 7 day	6.0	Lung fibroblast none	41.2
PBMC rest	5.2	Lung fibroblast TNF alpha + IL-	40.1
		1beta
PBMC PWM	4.7	Lung fibroblast IL-4	29.1
PBMC PHA-L	6.7	Lung fibroblast IL-9	44.8
Ramos (B cell) none	9.5	Lung fibroblast IL-13	3.7
Ramos (B cell) ionomycin	60.3	Lung fibroblast IFN gamma	61.1
B lymphocytes PWM	34.2	Dermal fibroblast CCD1070 rest	64.2
B lymphocytes CD40L and IL-4	97.3	Dermal fibroblast CCD1070 TNF	89.5
		alpha
EOL-1 dbcAMP	12.4	Dermal fibroblast CCD1070 IL-	34.4
		1beta
EOL-1 dbcAMP	1.2	Dermal fibroblast IFN gamma	43.2
PMA/ionomycin
Dendritic cells none	29.7	Dermal fibroblast IL-4	59.0
Dendritic cells LPS	4.7	Dermal Fibroblasts rest	48.6
Dendritic cells anti-CD40	6.9	Neutrophils TNFa + LPS	2.6
Monocytes rest	3.0	Neutrophils rest	12.3
Monocytes LPS	40.1	Colon	3.4
Macrophages rest	13.1	Lung	1.6
Macrophages LPS	4.7	Thymus	10.8
HUVEC none	9.8	Kidney	36.3
HUVEC starved	17.8

[0851] CNS_neurodegeneration_v1.0 Summary: Ag6090 This panel confirms the expression of this gene at moderate levels in the brain in an independent group of individuals. This gene appears to be slightly upregulated in the temporal cortex of Alzheimer's disease patients. Therefore, therapeutic modulation of the expression or function of this gene may decrease neuronal death and be of use in the treatment of this disease.

[0852] General_screening_panel_v1.5 Summary: Ag6089 Highest expression of this gene is seen in a brain cancer cell line (CT=28.3). This gene is widely expressed in this panel, with moderate expression seen in brain, colon, gastric, lung, breast, ovarian, and melanoma cancer cell lines. This expression profile suggests a role for this gene product in cell survival and proliferation. Modulation of this gene product may be useful in the treatment of cancer.

[0853] Among tissues with metabolic function, this gene is expressed at moderate to low levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression among these tissues suggests that this gene product may play a role in normal neuroendocrine and metabolic function and that disregulated expression of this gene may contribute to neuroendocrine disorders or metabolic diseases, such as obesity and diabetes.

[0854] Interestingly, this gene is expressed at much higher levels in the fetal liver (CT=29.3) when compared to the level of expression in the adult tissue (CT=32.6). This observation suggests that expression of this gene can be used to distinguish between the fetal and adult sources of this tissue. In addition, the relative overexpression of this gene in fetal liver suggests that the protein product may enhance growth or development of this organ 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.

[0855] 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.

[0856] Panel 1.2 Summary: Ag776 Expression of this gene is widespread in this panel, with highest expression detected in a lung cancer cell line (T=25). Please see Panel 1.5 for further discussion of expression and utility of this gene.

[0857] Panel 4.1D Summary: Ag6089 Highest expression of this gene is seen in chronically activated Th2 cells (CT=30.2). 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, thymus and kidney. This ubiquitous pattern of expression suggests that this gene product may be involved in homeostatic processes for these and other cell types and tissues. This pattern is in agreement with the expression profile in General_screening_panel_v1.5 and also suggests a role for the gene product in cell survival and proliferation. Therefore, modulation of the gene product with a functional therapeutic may lead to the alteration of functions associated with these cell types and lead to improvement of the symptoms of patients suffering from autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, and osteoarthritis.

[0858] X. CG164511-01: DORA Protein Precursor-Like Protein.

[0859] Expression of gene CG16451 1-01 was assessed using the primer-probe set Ag5882, described in Table XA.

TABLE XA
Probe Name Ag5882
			Start	SEQ ID
Primers	Sequence	Length	Position	No
Forward	5′-gccttcatactcctctccaaat-3′	22	392	263
Probe	TET-5′-caaaatccaaccctctaagaaagaaaga-3′-TAMRA	28	414	264
Reverse	5′-gccgagcactcttcttcttt-3′	20	460	265

[0860] Y. CG55060-01: SLPI-Like Protein.

[0861] Expression of gene CG55060-01 was assessed using the primer-probe set Ag588, described in Table YA. Results of the RTQ-PCR runs are shown in Tables YB, YC, YD, YE, YF, YG and YH.

TABLE YA
Probe Name Ag588
			Start	SEQ ID
Primers	Sequence	Length	Position	No
Forward	5′-tgccttcaccatgaagtcca-3′	20	9	266
Probe	TET-5′-cttcctggtgctgcttgccctgg-3′-TAMRA	23	42	267
Reverse	5′-agcccaaggtgccagagtt-3′	19	66	268

[0862]

TABLE YB
CNS_neurodegeneration_v1.0
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag588,		Ag588,
	Run		Run
Tissue Name	224758452	Tissue Name	224758452
AD 1 Hippo	8.1	Control (Path) 3 Temporal Ctx	5.2
AD 2 Hippo	75.8	Control (Path) 4 Temporal Ctx	2.2
AD 3 Hippo	100.0	AD 1 Occipital Ctx	7.9
AD 4 Hippo	15.7	AD 2 Occipital Ctx (Missing)	0.0
AD 5 Hippo	16.7	AD 3 Occipital Ctx	12.6
AD 6 Hippo	11.3	AD 4 Occipital Ctx	6.2
Control 2 Hippo	2.3	AD 5 Occipital Ctx	11.7
Control 4 Hippo	11.3	AD 6 Occipital Ctx	8.8
Control (Path) 3 Hippo	25.7	Control 1 Occipital Ctx	11.1
AD 1 Temporal Ctx	17.2	Control 2 Occipital Ctx	1.9
AD 2 Temporal Ctx	23.0	Control 3 Occipital Ctx	2.6
AD 3 Temporal Ctx	14.5	Control 4 Occipital Ctx	2.1
AD 4 Temporal Ctx	6.9	Control (Path) 1 Occipital Ctx	3.3
AD 5 Inf Temporal Ctx	2.3	Control (Path) 2 Occipital Ctx	2.8
AD 5 Sup Temporal Ctx	14.8	Control (Path) 3 Occipital Ctx	10.6
AD 6 Inf Temporal Ctx	9.7	Control (Path) 4 Occipital Ctx	2.0
AD 6 Sup Temporal Ctx	19.2	Control 1 Parietal Ctx	16.0
Control 1 Temporal Ctx	15.1	Control 2 Parietal Ctx	9.0
Control 2 Temporal Ctx	0.9	Control 3 Parietal Ctx	3.4
Control 3 Temporal Ctx	4.9	Control (Path) 1 Parietal Ctx	9.9
Control 3 Temporal Ctx	3.2	Control (Path) 2 Parietal Ctx	14.5
Control (Path) 1 Temporal Ctx	4.3	Control (Path) 3 Parietal Ctx	7.9
Control (Path) 2 Temporal Ctx	8.1	Control (Path) 4 Parietal Ctx	12.0

[0863]

TABLE YC
General_screening_panel_v1.5
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag588,		Ag588,
	Run		Run
Tissue Name	248445830	Tissue Name	248445830
Adipose	0.9	Renal ca. TK-10	0.0
Melanoma* Hs688(A).T	0.0	Bladder	1.0
Melanoma* Hs688(B).T	0.0	Gastric ca. (liver met.) NCI-N87	6.3
Melanoma* M14	0.0	Gastric ca. KATO III	0.2
Melanoma* LOXIMVI	0.0	Colon ca. SW-948	0.7
Melanoma* SK-MEL-5	0.0	Colon ca. SW480	0.2
Squamous cell carcinoma SCC-4	2.6	Colon ca.* (SW480 met) SW620	0.0
Testis Pool	0.2	Colon ca. HT29	0.0
Prostate ca.* (bone met) PC-3	0.6	Colon ca. HCT-116	0.0
Prostate Pool	0.1	Colon ca. CaCo-2	0.2
Placenta	0.0	Colon cancer tissue	0.8
Uterus Pool	0.4	Colon ca. SW1116	0.0
Ovarian ca. OVCAR-3	6.5	Colon ca. Colo-205	0.3
Ovarian ca. SK-OV-3	11.3	Colon ca. SW-48	1.4
Ovarian ca. OVCAR-4	6.4	Colon Pool	0.1
Ovarian ca. OVCAR-5	4.4	Small Intestine Pool	1.0
Ovarian ca. IGROV-1	4.5	Stomach Pool	0.2
Ovarian ca. OVCAR-8	0.1	Bone Marrow Pool	3.3
Ovary	0.9	Fetal Heart	0.0
Breast ca. MCF-7	0.1	Heart Pool	0.0
Breast ca. MDA-MB-231	0.0	Lymph Node Pool	0.1
Breast ca. BT 549	0.0	Fetal Skeletal Muscle	0.0
Breast ca. T47D	0.0	Skeletal Muscle Pool	0.2
Breast ca. MDA-N	0.0	Spleen Pool	0.0
Breast Pool	0.4	Thymus Pool	0.3
Trachea	100.0	CNS cancer (glio/astro) U87-MG	0.0
Lung	0.0	CNS cancer (glio/astro) U-118-MG	0.1
Fetal Lung	3.6	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	1.9	CNS cancer (astro) SNB-75	2.0
Lung ca. NCI-H146	0.0	CNS cancer (glio) SNB-19	2.8
Lung ca. SHP-77	0.0	CNS cancer (glio) SF-295	36.6
Lung ca. A549	0.4	Brain (Amygdala) Pool	0.0
Lung ca. NCI-H526	0.0	Brain (cerebellum)	0.0
Lung ca. NCI-H23	0.3	Brain (fetal)	0.0
Lung ca. NCI-H460	2.2	Brain (Hippocampus) Pool	0.0
Lung ca. HOP-62	0.3	Cerebral Cortex Pool	0.0
Lung ca. NCI-H522	0.0	Brain (Substantia nigra) Pool	0.0
Liver	0.3	Brain (Thalamus) Pool	0.0
Fetal Liver	0.0	Brain (whole)	0.0
Liver ca. HepG2	0.2	Spinal Cord Pool	0.3
Kidney Pool	0.1	Adrenal Gland	0.1
Fetal Kidney	0.0	Pituitary gland Pool	0.7
Renal ca. 786-0	0.0	Salivary Gland	20.4
Renal ca. A498	0.5	Thyroid (female)	0.1
Renal ca. ACHN	0.0	Pancreatic ca. CAPAN2	5.1
Renal ca. UO-31	0.3	Pancreas Pool	2.4

[0864]

TABLE YD
Oncology_cell_line_screening_panel_v3.1
	Rel.		Rel.
	Exp. (%)		Exp. (%)
	Ag588,		Ag588,
	Run		Run
Tissue Name	225138983	Tissue Name	225138983
Daoy Medulloblastoma/Cerebellum	0.3	Ca Ski_Cervical epidermoid	8.8
		carcinoma (metastasis)
TE671 Medulloblastom/Cerebellum	0.2	ES-2_Ovarian clear cell carcinoma	0.0
D283 Med	0.0	Ramos/6 h stim_Stimulated with	0.0
Medulloblastoma/Cerebellum		PMA/ionomycin 6 h
PFSK-1 Primitive	0.0	Ramos/14 h stim_Stimulated with	0.0
Neuroectodermal/Cerebellum		PMA/ionomycin 14 h
XF-498_CNS	0.0	MEG-01_Chronic myelogenous	0.2
		leukemia (megokaryoblast)
SNB-78_CNS/glioma	0.0	Raji_Burkitt's lymphoma	0.0
SF-268_CNS/glioblastoma	0.0	Daudi_Burkitt's lymphoma	0.0
T98G_Glioblastoma	6.2	U266_B-cell	0.0
		plasmacytoma/myeloma
SK-N-SH_Neuroblastoma	0.0	CA46_Burkitt's lymphoma	0.0
(metastasis)
SF-295_CNS/glioblastoma	9.3	RL_non-Hodgkin's B-cell lymphoma	0.0
Cerebellum	0.1	JM1_pre-B-cell lymphoma/leukemia	0.0
Cerebellum	0.3	Jurkat_T cell leukemia	0.0
NCI-H292_Mucoepidermoid lung	24.7	TF-1_Erythroleukemia	0.0
ca.
DMS-114_Small cell lung cancer	0.0	HUT 78_T-cell lymphoma	0.0
DMS-79_Small cell lung	0.0	U937_Histiocytic lymphoma	2.3
cancer/neuroendocrine
NCI-H146_Small cell lung	0.0	KU-812_Myelogenous leukemia	0.0
cancer/neuroendocrine
NCI-H526_Small cell lung	0.0	769-P_Clear cell renal ca.	0.0
cancer/neuroendocrine
NCI-N417_Small cell lung	0.0	Caki-2_Clear cell renal ca.	0.4
cancer/neuroendocrine
NCI-H82_Small cell lung	0.0	SW 839_Clear cell renal ca.	0.0
cancer/neuroendocrine
NCI-H157_Squamous cell lung	0.0	G401_Wilms' tumor	0.0
cancer (metastasis)
NCI-H1155_Large cell lung	0.1	Hs766T_Pancreatic ca. (LN	14.3
cancer/neuroendocrine		metastasis)
NCI-H1299_Large cell lung	0.0	CAPAN-1_Pancreatic	15.6
cancer/neuroendocrine		adenocarcinoma (liver metastasis)
NCI-H727_Lung carcinoid	0.4	SU86.86_Pancreatic carcinoma	30.8
		(liver metastasis)
NCI-UMC-11_Lung carcinoid	0.0	BxPC-3_Pancreatic adenocarcinoma	18.9
LX-1_Small cell lung cancer	0.8	HPAC_Pancreatic adenocarcinoma	7.5
Colo-205_Colon cancer	4.6	MIA PaCa-2_Pancreatic ca.	0.0
KM12_Colon cancer	0.2	CFPAC-1_Pancreatic ductal	10.9
		adenocarcinoma
KM20L2_Colon cancer	0.6	PANC-1_Pancreatic epithelioid	0.1
		ductal ca.
NCI-H716_Colon cancer	0.0	T24_Bladder ca. (transitional cell)	5.1
SW-48_Colon adenocarcinoma	17.3	5637_Bladder ca.	26.4
SW1116_Colon adenocarcinoma	0.1	HT-1197_Bladder ca.	1.4
LS 174T_Colon adenocarcinoma	5.0	UM-UC-3_Bladder ca. (transitional	0.0
		cell)
SW-948_Colon adenocarcinoma	8.0	A204_Rhabdomyosarcoma	0.0
SW-480_Colon adenocarcinoma	1.5	HT-1080_Fibrosarcoma	0.0
NCI-SNU-5_Gastric ca.	0.1	MG-63_Osteosarcoma (bone)	0.6
KATO III_Stomach	0.5	SK-LMS-1_Leiomyosarcoma	0.0
		(vulva)
NCI-SNU-16_Gastric ca.	0.0	SJRH30_Rhabdomyosarcoma (met	0.0
		to bone marrow)
NCI-SNU-1_Gastric ca.	1.8	A431_Epidermoid ca.	18.9
RF-1_Gastric adenocarcinoma	0.2	WM266-4_Melanoma	0.0
RF-48_Gastric adenocarcinoma	0.3	DU 145_Prostate	2.0
MKN-45_Gastric ca.	13.8	MDA-MB-468_Breast	34.9
		adenocarcinoma
NCI-N87_Gastric ca.	13.1	SSC-4_Tongue	18.6
OVCAR-5_Ovarian ca.	14.9	SSC-9_Tongue	11.8
RL95-2_Uterine carcinoma	100.0	SSC-15_Tongue	24.7
HelaS3_Cervical adenocarcinoma	25.7	CAL 27_Squamous cell ca. of	21.3
		tongue

[0865]

TABLE YE
Panel 1.1
	Rel.		Rel.
	Ex.(%)		Exp.(%)
	Ag588,		Ag588,
	Run		Run
Tissue Name	108446724	Tissue Name	108446724
Adrenal gland	0.1	Renal ca. UO-31	0.0
Bladder	3.6	Renal ca. .RXF 393	0.0
Brain (amygdala)	0.0	Liver	1.6
Brain (cerebellum)	0.0	Liver (fetal)	0.2
Brain (hippocampus)	0.0	Liver ca.(hepatoblast) HepG2	0.0
Brain (substantia nigra)	0.1	Lung	8.6
Brain (thalamus)	0.0	Lung (fetal)	3.0
Cerebral Cortex	0.0	Lung ca.(non-s.cell) HOP-62	0.5
Brain (fetal)	0.0	Lung ca. (large cell)NCI-H460	2.6
Brain (whole)	0.0	Lung ca. (non-s.cell) NCI-H23	0.2
glio/astro U-118-MG	0.0	Lung ca. (non-s.cl) NCI-H522	0.0
astrocytoma SF-539	0.0	Lung ca. (non-sm. cell) A549	1.6
astrocytoma SNB-75	0.2	Lung ca. (s.cell var.) SHP-77	0.0
astrocytoma SW1783	0.0	Lung ca. (small cell) LX-1	1.6
glioma U251	0.0	Lung ca. (small cell) NCI-H69	0.1
glioma SF-295	13.8	Lung ca. (squam.) SW 900	0.4
glioma SNB-19	0.0	Lung ca. (squam.) NCI-H596	0.0
glio/astro U87-MG	0.0	Lymph node	0.3
neuro*; met SK-N-AS	0.0	Spleen	0.0
Mammary gland	1.8	Thymus	0.2
Breast ca. BT-549	0.1	Ovary	0.5
Breast ca. MDA-N	0.0	Ovarian ca. IGROV-1	4.6
Breast ca.* (pl.ef) T47D	0.1	Ovarian ca. OVCAR-3	5.4
Breast ca.* (pl.ef) MCF-7	0.1	Ovarian ca. OVCAR-4	16.5
Breast ca.* (pl.ef) MDA-MB-231	0.0	Ovarian ca. OVCAR-5	2.6
Small intestine	0.4	Ovarian ca. OVCAR-8	0.2
Colorectal	0.4	Ovarian ca.* (ascites) SK-OV-3	7.9
Colon ca. HT29	0.0	Pancreas	0.4
Colon ca. CaCo-2	0.0	Pancreatic ca. CAPAN 2	1.2
Colon ca. HCT-15	0.4	Pituitary gland	4.3
Colon ca. HCT-116	0.0	Placenta	0.1
Colon ca. HCC-2998	1.4	Prostate	1.2
Colon ca. SW480	0.0	Prostate ca.* (bone met) PC-3	0.6
Colon ca.* SW620 (SW480 met)	0.0	Salivary gland	64.2
Stomach	1.1	Trachea	100.0
Gastric ca. (liver met) NCI-N87	4.3	Spinal cord	1.6
Heart	0.9	Testis	0.3
Skeletal muscle (Fetal)	0.0	Thyroid	0.4
Skeletal muscle	1.5	Uterus	0.4
Endothelial cells	0.0	Melanoma M14	0.0
Heart (Fetal)	0.0	Melanoma LOX IMVI	0.0
Kidney	0.6	Melanoma UACC-62	0.0
Kidney (fetal)	0.0	Melanoma SK-MEL-28	0.0
Renal ca. 786-0	0.0	Melanoma* (met) SK-MEL-5	0.0
Renal ca. A498	1.0	Melanoma Hs688(A).T	0.0
Renal ca. ACHN	0.0	Melanoma* (met) Hs688(B).T	0.0
Renal ca. TK-10	0.0

[0866]

TABLE YF
Panel 2D
	Rel.	Rel.		Rel.	Rel.
	Exp. (%)	Exp. (%)		Exp. (%)	Exp. (%)
	Ag588,	Ag588,		Ag588,	Ag588,
	Run	Run		Run	Run
Tissue Name	144773993	144872213	Tissue Name	144773993	144872213
Normal Colon	4.8	4.4	Kidney Margin	1.7	2.1
			8120608
CC Well to Mod Diff	1.3	1.2	Kidney Cancer	0.0	0.0
(ODO3866)			8120613
CC Margin	0.9	0.8	Kidney Margin	0.9	0.7
(ODO3866)			8120614
CC Gr.2 rectosigmoid	1.8	1.8	Kidney Cancer	27.4	26.8
(ODO3868)			9010320
CC Margin	0.0	0.1	Kidney Margin	2.4	2.2
(ODO3868)			9010321
CC Mod Diff	3.1	2.9	Normal Uterus	0.1	0.1
(ODO3920)
CC Margin	0.5	0.4	Uterus Cancer	63.3	61.6
(ODO3920)			064011
CC Gr.2 ascend colon	2.3	1.8	Normal Thyroid	1.7	1.6
(ODO3921)
CC Margin	0.4	0.4	Thyroid Cancer	13.8	12.3
(ODO3921)			064010
CC from Partial	1.8	2.0	Thyroid Cancer	1.3	1.0
Hepatectomy			A302152
(ODO4309) Mets
Liver Margin	2.4	2.2	Thyroid Margin	0.5	0.5
(ODO4309)			A302153
Colon mets to lung	5.3	5.1	Normal Breast	5.5	5.4
(OD04451-01)
Lung Margin	32.8	35.8	Breast Cancer	0.0	0.0
(OD04451-02)			(OD04566)
Normal Prostate	5.0	4.8	Breast Cancer	0.9	0.9
6546-1			(OD04590-01)
Prostate Cancer	0.3	0.2	Breast Cancer Mets	0.7	0.8
(OD04410)			(OD04590-03)
Prostate Margin	0.2	0.2	Breast Cancer	0.1	0.2
(OD04410)			Metastasis
			(OD04655-05)
Prostate Cancer	0.7	0.8	Breast Cancer	1.2	0.9
(OD04720-01)			064006
Prostate Margin	1.8	1.5	Breast Cancer 1024	4.1	3.7
(OD04720-02)
Normal Lung 061010	56.3	55.1	Breast Cancer	1.7	1.6
			9100266
Lung Met to Muscle	0.0	0.0	Breast Margin	1.6	1.3
(ODO4286)			9100265
Muscle Margin	24.5	26.1	Breast Cancer	12.9	12.4
(ODO4286)			A209073
Lung Malignant	42.0	41.8	Breast Margin	6.1	6.0
Cancer (OD03126)			A209073
Lung Margin	40.3	42.9	Normal Liver	1.0	1.0
(OD03126)
Lung Cancer	27.4	28.9	Liver Cancer	14.4	14.2
(OD04404)			064003
Lung Margin	42.6	39.2	Liver Cancer 1025	2.5	2.4
(OD04404)
Lung Cancer	13.7	12.8	Liver Cancer 1026	4.2	4.7
(OD04565)
Lung Margin	18.3	18.4	Liver Cancer	5.3	4.7
(OD04565)			6004-T
Lung Cancer	6.4	6.2	Liver Tissue	0.1	0.1
(OD04237-01)			6004-N
Lung Margin	12.8	12.2	Liver Cancer	5.1	4.8
(OD04237-02)			6005-T
Ocular Mel Met to	0.0	0.0	Liver Tissue	1.4	1.4
Liver (ODO4310)			6005-N
Liver Margin	3.6	3.6	Normal Bladder	2.7	2.3
(ODO4310)
Melanoma Mets to	0.4	0.4	Bladder Cancer	2.7	2.8
Lung (OD04321)			1023
Lung Margin	77.9	76.3	Bladder Cancer	8.2	7.3
(OD04321)			A302173
Normal Kidney	1.6	1.5	Bladder Cancer	2.0	1.8
			(OD04718-01)
Kidney Ca, Nuclear	3.3	3.2	Bladder Normal	0.9	0.9
grade 2 (OD04338)			Adjacent
			(OD04718-03)
Kidney Margin	3.0	3.0	Normal Ovary	0.6	0.5
(OD04338)
Kidney Ca Nuclear	6.7	6.7	Ovarian Cancer	100.0	100.0
grade 1/2 (OD04339)			064008
Kidney Margin	0.7	0.6	Ovarian Cancer	21.9	20.7
(OD04339)			(OD04768-07)
Kidney Ca, Clear cell	0.0	0.0	Ovary Margin	4.1	3.7
type (OD04340)			(OD04768-08)
Kidney Margin	2.5	2.3	Normal Stomach	2.3	2.0
(OD04340)
Kidney Ca, Nuclear	7.1	6.8	Gastric Cancer	0.5	0.4
grade 3 (OD04348)			9060358
Kidney Margin	1.8	1.8	Stomach Margin	2.6	2.2
(OD04348)			9060359
Kidney Cancer	0.3	0.2	Gastric Cancer	5.4	5.7
(OD04622-01)			9060395
Kidney Margin	2.3	2.4	Stomach Margin	4.9	4.7
(OD04622-03)			9060394
Kidney Cancer	9.2	8.5	Gastric Cancer	14.1	13.9
(OD04450-01)			9060397
Kidney Margin	1.5	1.5	Stomach Margin	5.1	4.4
(OD04450-03)			9060396
Kidney Cancer	33.2	30.8	Gastric Cancer	0.2	0.2
8120607			064005

[0867]

TABLE YG
Panel 4D
	Rel.		Rel.
	Exp (%)		Exp.(%)
	Ag588,		Ag588,
	Run		Run
Tissue Name	163588119	Tissue Name	163588119
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 +	0.0
		IL-1beta
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 +	3.7
		IL1beta
Primary Th2 rest	0.0	Small airway epithelium none	53.6
Primary Tr1 rest	0.0	Small airway epithelium TNF alpha +	100.0
		IL-1beta
CD45RA CD4 lymphocyte act	0.0	Coronery artery SMC rest	0.0
CD45RO CD4 lymphocyte act	0.0	Coronery artery SMC TNF alpha +	0.0
		IL-1beta
CD8 lymphocyte act	1.4	Astrocytes rest	0.0
Secondary CD8 lymphocyte rest	0.0	Astrocytes TNF alpha + IL-1beta	0.9
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	0.7
CH11
LAK cells rest	0.0	CCD1106 (Keratinocytes)	0.6
		TNF alpha + IL-1beta
LAK cells IL-2	0.0	Liver cirrhosis	1.7
LAK cells IL-2 + IL-12	0.0	Lupus kidney	9.9
LAK cells IL-2 + IFN gamma	0.0	NCI-H292 none	49.0
LAK cells IL-2 + IL-18	0.0	NCI-H292 IL-4	61.6
LAK cells PMA/ionomycin	0.0	NCI-H292 IL-9	83.5
NK Cells IL-2 rest	0.0	NCI-H292 IL-13	37.4
Two Way MLR 3 day	0.0	NCI-H292 IFN gamma	43.2
Two Way MLR 5 day	0.0	HPAEC none	0.0
Two Way MLR 7 day	0.0	HPAEC TNF alpha + IL-1beta	0.0
PBMC rest	0.0	Lung fibroblast none	0.0
PBMC PWM	0.2	Lung fibroblast TNF alpha + IL-1	0.0
		beta
PBMC PHA-L	0.0	Lung fibroblast IL-4	0.0
Ramos (B cell) none	0.0	Lung fibroblast IL-9	0.0
Ramos (B cell) ionomycin	0.0	Lung fibroblast IL-13	0.0
B lymphocytes PWM	0.2	Lung fibroblast IFN gamma	0.0
B lymphocytes CD40L and IL-4	0.0	Dermal fibroblast CCD1070 rest	0.0
EOL-1 dbcAMP	0.2	Dermal fibroblast CCD1070 TNF	0.0
		alpha
EOL-1 dbcAMP	0.0	Dermal fibroblast CCD1070 IL-1	0.0
PMA/ionomycin		beta
Dendritic cells none	0.0	Dermal fibroblast IFN gamma	0.0
Dendritic cells LPS	0.0	Dermal fibroblast IL-4	0.0
Dendritic cells anti-CD40	0.0	IBD Colitis 2	0.0
Monocytes rest	0.0	IBD Crohn's	0.1
Monocytes LPS	0.1	Colon	0.7
Macrophages rest	0.0	Lung	36.3
Macrophages LPS	0.0	Thymus	1.4
HUVEC none	0.0	Kidney	3.9
HUVEC starved	0.0

[0868]

TABLE YH
Panel 5D
	Rel.		Rel.
	Exp (%)		Exp.(%)
	Ag588,		Ag588,
	Run		Run
Tissue Name	248989995	Tissue Name	248989995
97457_Patient-02go_adipose	100.0	94709_Donor 2 AM - A_adipose	1.8
97476_Patient-07sk_skeletal	7.8	94710_Donor 2 AM - B_adipose	1.2
muscle
97477_Patient-07ut_uterus	0.3	94711_Donor 2 AM - C_adipose	1.0
97478_Patient-07pl_placenta	1.8	94712_Donor 2 AD - A_adipose	2.6
97481_Patient-08sk_skeletal	9.0	94713_Donor 2 AD - B_adipose	3.6
muscle
97482_Patient-08ut_uterus	0.4	94714_Donor 2 AD - C_adipose	3.0
97483_Patient-08pl_placenta	1.1	94742_Donor 3 U - A_Mesenchymal	0.0
		Stem Cells
97486_Patient-09sk_skeletal	7.6	94743_Donor 3 U - B_Mesenchymal	0.2
muscle		Stem Cells
97487_Patient-09ut_uterus	1.5	94730_Donor 3 AM - A_adipose	2.4
97488_Patient-09pl_placenta	0.4	94731_Donor 3 AM - B_adipose	1.0
97492_Patient-10ut_uterus	7.1	94732_Donor 3 AM - C_adipose	1.4
97493_Patient-10pl_placenta	0.3	94733_Donor 3 AD - A_adipose	2.8
97495_Patient-11go_adipose	63.3	94734_Donor 3 AD - B_adipose	1.1
97496_Patient-11sk_skeletal	6.9	94735_Donor 3 AD - C_adipose	2.8
muscle
97497_Patient-11ut_uterus	1.0	77138_Liver_HepG2untreated	0.1
97498_Patient-11pl_placenta	0.5	73556_Heart_Cardiac stromal cells	0.0
		(primary)
97500_Patient-12go_adipose	52.5	81735_Small Intestine	58.2
97501_Patient-12sk_skeletal	3.1	72409_Kidney_Proximal Convoluted	13.0
muscle		Tubule
97502_Patient-12ut_uterus	0.2	82685_Small intestine_Duodenum	0.2
97503_Patient-12pl_placenta	0.1	90650_Adrenal_Adrenocortical	0.1
		adenoma
94721_Donor 2 U -	0.0	72410_Kidney_HRCE	15.4
A_Mesenchymal Stem Cells
94722_Donor 2 U -	0.1	72411_Kidney_HRE	3.9
B_Mesenchymal Stem Cells
94723_Donor 2 U -	0.0	73139_Uterus_Uterine smooth	0.0
C_Mesenchymal Stem Cells		muscle cells

[0869] CNS_neurodegeneration_v1.0 Summary: Ag588 This panel confirms the expression of this gene at moderate levels in the brain in an independent group of individuals. This gene appears to be slightly upregulated in the temporal cortex of Alzheimer's disease patients. Therefore, therapeutic modulation of the expression or function of this gene may decrease neuronal death and be of use in the treatment of this disease.

[0870] General_screening_panel_v1.5 Summary: Ag588 Highest expression of this gene is seen in the trachea (CT=18). High levels of expression are also seen in a cluster of ovarian cancer cell line samples, as well as in cell line samples derived from pancreatic cancer, brain cancer, colon cancer, gastric cancer, and squamous cell carcinoma. Thus, this gene product may be involved in these diseases.

[0871] Oncology_cell_line_screening_panel_v3.1 Summary: Ag588 Highest expression is seen in a uterine cancer cell lien (CT=22.8). High levels of expression are also seen in brain, gastric, colon, ovarian, pancreatic, breast, and bladder cancer cell lines.

[0872] Panel 1.1 Summary: Ag588 Highest expression of this gene is seen in the trachea (CT=18). Overall, expression is in agreement with Panel 1.5. Please see that panel for discussion of utility of this gene.

[0873] Panel 2D Summary: Ag588 Two experiments with the same probe and primer produce results that are in excellent agreement. Highest expression is seen in an ovarian cancer sample (CTs=22). In addition, this gene appears to be overexpressed in samples from ovarian, uterine, thyroid and kidney cancers when compared to expression in normal adjacent tissue. Conversely, this gene appears to be more highly expressed in normal lung tissue than in adjacent lung tumor. This gene encodes secretory leucocyte protease inhibitor (SLPI), a potent inhibitor of granulocyte elastase and cathepsin G, as well as pancreatic enzymes like trypsin, chymotrypsin and pancreatic elastase. SLPI has also been shown to inhibit HIV-1 infections by blocking viral DNA synthesis. Antileucoprotease (ALP) is generally considered as a specific marker for glandular serous cells that plays a major role in the defence of the respiratory tract against proteolytic damage. Goselink et al. demonstrated that the COOH-terminal domain of ALP contains proteinase inhibitory activity and illustrated that proteinase inhibitors play an important role in the in vitro growth of hematopoietic cells by the neutralization of proteinases produced by bone marrow accessory cells. (J Exp Med Oct. 1, 1996;184(4):1305-12) Thus, the over-expression of this gene in these tumors suggests that expression of this gene could be used to differentiate between these cancer samples and other samples on this panel and as a marker of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene may be useful in the treatment of ovarian, uterine, thyroid, and kidney cancers.

[0874] Panel 4D Summary: Ag588 Highest expression is seen in TNF-a/IL1-b treated small airway epithelium. High levels of expression are also seen in untreated small airway epithelium,normal lung, and a cluster of treated and untreated samples derived from the NCI-H292 cell line, a human airway epithelial cell line that produces mucins. Mucus overproduction is an important feature of bronchial asthma and chronic obstructive pulmonary disease samples. The expression of the transcript in this mucoepidermoid cell line that is often used as a model for airway epithelium (NCI-H292 cells) and in small airway epithelium 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.

[0875] Panel 5D Summary: Ag588 Prominent expression of this gene is seen in adipose (CTs=26-27). Thus, expression of this gene could be used to differentiate between the adipose derived samples and other samples on this panel and as a marker of this tissue. Furthermore, modulation of this gene product may be useful in the treatment of obesity and diabetes.

[0876] Z. CG56972-01, CG56972-02 and CG56972-03: NMB-Soluble-Like Protein.

[0877] Expression of gene CG56972-01, CG56972-02 and CG56972-03 was assessed using the primer-probe sets Ag817 and Ag5968, described in Tables ZA and ZB. Results of the RTQ-PCR runs are shown in Tables ZC, ZD, ZE, ZF, ZG, ZH, ZI, ZJ, ZK, ZL, ZM, ZN and ZO. Please note that CG56972-02 represents a full-length physical clone of the CG56972-0l gene, validating the prediction of the gene sequence. Also, Ag5968 is specific for CG56972-03.

TABLE ZA
Probe Name Ag817
			Start	SEQ ID
Primers	Sequence	Length	Position	No
Forward	5′-tcaatggaaccttcagcctta-3′	21	543	269
Probe	TET-5′-ctcactgtgaaagctgcagcaccag-3′-TAMRA	25	516	270
Reverse	5′-gaaggggtgggttttgaag-3′	19	464	271

[0878]

TABLE ZB
Probe Name Ag5968
			Start	SEQ ID
Primers	Sequencs	Length	Position	No
Forward	5′-cagttttcatcaggaatcctactc-3′	24	371	272
Probe	TET-5′-tatgattcaaacaccccaggacctgc	26	416	273
	-3′-TAMRA
Reverse	5′-cccttctttagcaactactctaaaatct-3	28	442	274
	′

[0879]

TABLE ZC
AI_comprehensive panel_v1.0
	Rel.		Rel.
	Exp.(%)		Exp.(%)
	Ag817,		Ag817,
	Run		Run
Tissue Name	247834306	Tissue Name	247834306
110967 COPD-F	37.1	112427 Match Control Psoriasis-F	53.2
110980 COPD-F	25.3	112418 Psoriasis-M	35.8
110968 COPD-M	34.6	112723 Match Control Psoriasis-M	0.8
110977 COPD-M	50.3	112419 Psoriasis-M	53.2
110989 Emphysema-F	33.7	112424 Match Control Psoriasis-M	12.2
110992 Emphysema-F	16.6	112420 Psoriasis-M	47.3
110993 Emphysema-F	29.7	112425 Match Control Psoriasis-M	39.0
110994 Emphysema-F	13.3	104689 (MF) OA Bone-Backus	24.8
110995 Emphysema-F	25.9	104690 (MF) Adj “Normal”	5.5
		Bone-Backus
110996 Emphysema-F	6.1	104691 (MF) OA Synovium-Backus	54.3
110997 Asthma-M	24.5	104692 (BA) OA Cartilage-Backus	1.9
111001 Asthma-F	23.8	104694 (BA) OA Bone-Backus	41.2
111002 Asthma-F	24.8	104695 (BA) Adj “Normal”	4.2
		Bone-Backus
111003 Atopic Asthma-F	25.5	104696 (BA) OA Synovium-Backus	82.4
111004 Atopic Asthma-F	13.9	104700 (SS) OA Bone-Backus	5.0
111005 Atopic Asthma-F	10.5	104701 (SS) Adj “Normal”	16.4
		Bone-Backus
111006 Atopic Asthma-F	3.4	104702 (SS) OA Synovium-Backus	81.8
111417 Allergy-M	14.5	117093 OA Cartilage Rep7	27.2
112347 Allergy-M	0.5	112672 OA Bone5	100.0
112349 Normal Lung-F	0.4	112673 OA Synovium5	45.7
112357 Normal Lung-F	11.4	112674 OA Synovial Fluid cells5	42.0
112354 Normal Lung-M	10.9	117100 OA Cartilage Rep14	21.8
112374 Crohns-F	13.2	112756 OA Bone9	2.6
112389 Match Control Crohns-F	42.3	112757 OA Synovium9	3.6
112375 Crohns-F	14.6	112758 OA Synovial Fluid Cells9	14.6
112732 Match Control Crohns-F	5.0	117125 RA Cartilage Rep2	31.9
112725 Crohns-M	0.9	113492 Bone2 RA	17.7
112387 Match Control	20.0	113493 Synovium2 RA	11.9
Crohns-M
112378 Crohns-M	0.8	113494 Syn Fluid Cells RA	14.4
112390 Match Control	65.5	113499 Cartilage4 RA	14.2
Crohns-M
112726 Crohns-M	21.2	113500 Bone4 RA	14.0
112731 Match Control	19.5	113501 Synovium4 RA	11.7
Crohns-M
112380 Ulcer Col-F	17.3	113502 Syn Fluid Cells4 RA	6.6
112734 Match Control Ulcer	12.4	113495 Cartilage3 RA	21.8
Col-F
112384 Ulcer Col-F	32.3	113496 Bone3 RA	21.9
112737 Match Control Ulcer	18.6	113497 Synovium3 RA	11.3
Col-F
112386 Ulcer Col-F	4.4	113498 Syn Fluid Cells3 RA	25.3
112738 Match Control Ulcer	3.0	117106 Normal Cartilage Rep20	14.8
Col-F
112381 Ulcer Col-M	35.8	113663 Bone3 Normal	0.5
112735 Match Control Ulcer	5.4	113664 Synoviun3 Normal	0.1
Col-M
112382 Ulcer Col-M	33.4	113665 Syn Fluid Cells3 Normal	0.2
112394 Match Control Ulcer	15.0	117107 Normal Cartilage Rep22	12.9
Col-M
112383 Ulcer Col-M	27.5	113667 Bone4 Normal	13.1
112736 Match Control Ulcer	32.1	113668 Synovium4 Normal	20.0
Col-M
112423 Psoriasis-F	17.8	113669 Syn Fluid Cells4 Normal	24.8

[0880]

TABLE ZD
Ardais_Panel_v.1.0
			Rel.
	Rel. Exp.(%)		Exp.(%)
	Ag17,		Ag817,
	Run		Run
Tissue Name	263526495	Tissue Name	263526495
136799_Lung cancer(362)	91.4	136787_lung cancer(356)	7.0
136800_Lung NAT(363)	85.9	136788_lung NAT(357)	8.2
136813_Lung cancer(372)	100.0	136806_Lung cancer(36B)	14.3
136814_Lung NAT(373)	5.6	136807_Lung NAT(36C)	0.9
136815_Lung cancer(374)	6.0	136789_lung cancer(358)	20.6
136816_Lung NAT(375)	12.7	136802_Lung cancer(365)	10.4
136791_Lung cancer(35A)	30.1	136803_Lung cancer(368)	4.5
136795_Lung cancer(35E)	20.7	136804_Lung cancer(369)	25.0
136797_Lung cancer(360)	10.7	136811_Lung cancer(370)	3.8
136794_lung NAT(35D)	9.9	136810_Lung NAT(36F)	22.4
136818_Lung NAT(377)	3.6

[0881]

TABLE ZE
CNS_neurodegeneration_v1.0
	Rel.		Rel.
	Exp.(%)		Exp.(%)
	Ag5968,		Ag5968,
	Run		Run
Tissue Name	248589036	Tissue Name	248589036
AD 1 Hippo	25.7	Control (Path) 3 Temporal Ctx	9.5
AD 2 Hippo	71.2	Control (Path) 4 Temporal Ctx	31.9
AD 3 Hippo	29.1	AD 1 Occipital Ctx	24.3
AD 4 Hippo	15.1	AD 2 Occipital Ctx (Missing)	0.3
AD 5 Hippo	57.4	AD 3 Occipital Ctx	8.8
AD 6 Hippo	64.2	AD 4 Occipital Ctx	20.4
Control 2 Hippo	19.2	AD 5 Occipital Ctx	17.0
Control 4 Hippo	29.5	AD 6 Occipital Ctx	38.7
Control (Path) 3 Hippo	35.1	Control 1 Occipital Ctx	1.6
AD 1 Temporal Ctx	34.6	Control 2 Occipital Ctx	17.4
AD 2 Temporal Ctx	50.0	Control 3 Occipital Ctx	13.8
AD 3 Temporal Ctx	14.5	Control 4 Occipital Ctx	14.7
AD 4 Temporal Ctx	25.0	Control (Path) 1 Occipital Ctx	36.9
AD 5 Inf Temporal Ctx	79.0	Control (Path) 2 Occipital Ctx	18.3
AD 5 Sup Temporal Ctx	80.1	Control (Path) 3 Occipital Ctx	1.1
AD 6 Inf Temporal Ctx	100.0	Control (Path) 4 Occipital Ctx	23.0
AD 6 Sup Temporal Ctx	98.6	Control 1 Parietal Ctx	7.7
Control 1 Temporal Ctx	28.5	Control 2 Parietal Ctx	83.5
Control 2 Temporal Ctx	20.4	Control 3 Parietal Ctx	11.0
Control 3 Temporal Ctx	23.7	Control (Path) 1 Parietal Ctx	36.1
Control 3 Temporal Ctx	20.9	Control (Path) 2 Parietal Ctx	34.2
Control (Path) 1 Temporal Ctx	38.4	Control (Path) 3 Parietal Ctx	0.7
Control (Path) 2 Temporal Ctx	41.2	Control (Path) 4 Parietal Ctx	27.4

[0882]

TABLE ZF
General_screening_panel_v1.5
	Rel.	Rel.		Rel.	Rel.
	Exp. (%)	Exp. (%)		Exp. (%)	Exp. (%)
	Ag5968,	Ag817,		Ag5968,	Ag817,
	Run	Run		Run	Run
Tissue Name	248220123	248592794	issue Name	248220123	248592794
Adipose	4.2	12.3	Renal ca. TK-10	0.0	0.0
Melanoma*	2.0	11.0	Bladder	2.4	11.0
Hs688(A).T
Melanoma*	1.5	7.9	Gastric ca. (liver	2.1	12.4
Hs688(B).T			met.) NCI-N87
Melanoma* M14	29.1	100.0	Gastric ca. KATO	0.0	0.0
			III
Melanoma*	0.0	0.1	Colon ca. SW-948	0.0	0.0
LOXIMVI
Melanoma*	12.2	72.2	Colon ca. SW480	0.0	0.0
SK-MEL-5
Squamous cell	0.1	0.6	Colon ca.* (SW480	0.0	0.0
carcinoma SCC-4			met) SW620
Testis Pool	1.0	6.7	Colon ca. HT29	0.0	0.0
Prostate ca.* (bone	0.0	0.0	Colon ca. HCT-116	0.0	0.0
met) PC-3
Prostate Pool	0.7	3.1	Colon ca. CaCo-2	0.0	0.0
Placenta	3.8	16.8	Colon cancer tissue	4.0	16.6
Uterus Pool	5.0	31.2	Colon ca. SW1116	0.0	0.0
Ovarian ca.	0.4	2.1	Colon ca. Colo-205	0.0	0.0
OVCAR-3
Ovarian ca. SK-OV-3	0.0	0.0	Colon ca. SW-48	0.0	0.0
Ovarian ca.	0.1	1.0	Colon Pool	3.8	18.2
OVCAR-4
Ovarian ca.	0.1	0.5	Small Intestine Pool	2.5	11.5
OVCAR-5
Ovarian ca.	0.1	0.4	Stomach Pool	1.4	6.2
IGROV-1
Ovarian ca.	0.2	0.9	Bone Marrow Pool	2.7	16.6
OVCAR-8
Ovary	0.5	2.3	Fetal Heart	4.3	23.0
Breast ca. MCF-7	0.0	0.0	Heart Pool	2.6	13.7
Breast ca.	0.0	0.0	Lymph Node Pool	3.7	18.8
MDA-MB-231
Breast ca. BT 549	0.3	1.5	Fetal Skeletal	0.4	1.8
			Muscle
Breast ca. T47D	0.3	2.0	Skeletal Muscle	0.5	2.9
			Pool
Breast ca. MDA-N	2.1	12.4	Spleen Pool	0.3	0.8
Breast Pool	3.7	15.0	Thymus Pool	1.5	7.3
Trachea	1.5	4.2	CNS cancer	3.6	12.5
			(glio/astro)
			U87-MG
Lung	0.7	2.8	CNS cancer	4.0	14.9
			(glio/astro)
			U-118-MG
Fetal Lung	0.3	1.1	CNS cancer	0.0	0.3
			(neuro; met)
			SK-N-AS
Lung ca. NCI-N417	0.0	0.0	CNS cancer (astro)	3.7	23.0
			SF-539
Lung ca. LX-1	0.0	0.0	CNS cancer (astro)	3.4	17.3
			SNB-75
Lung ca. NCI-H146	0.0	0.0	CNS cancer (glio)	0.1	0.4
			SNB-19
Lung ca. SHP-77	0.0	0.0	CNS cancer (glio)	2.2	16.6
			SF-295
Lung ca. A549	0.0	0.0	Brain (Amygdala)	0.1	0.3
			Pool
Lung ca. NCI-H526	0.0	0.0	Brain (cerebellum)	0.1	0.5
Lung ca. NCI-H23	0.0	0.0	Brain (fetal)	0.2	0.7
Lung ca. NCI-H460	0.0	0.0	Brain	0.2	1.2
			(Hippocampus)
			Pool
Lung ca. HOP-62	0.0	0.4	Cerebral Cortex	0.3	1.3
			Pool
Lung ca. NCI-H522	0.0	0.0	Brain (Substantia	0.2	0.5
			nigra) Pool
Liver	0.1	0.3	Brain (Thalamus)	0.3	0.8
			Pool
Fetal Liver	0.2	0.5	Brain (whole)	0.2	1.5
Liver ca. HepG2	0.0	0.0	Spinal Cord Pool	100.0	2.2
Kidney Pool	6.4	24.7	Adrenal Gland	0.5	2.5
Fetal Kidney	0.5	2.8	Pituitary gland Pool	0.1	0.4
Renal ca. 786-0	0.0	0.0	Salivary Gland	0.4	0.6
Renal ca. A498	0.8	6.4	Thyroid (female)	0.4	1.6
Renal ca. ACHN	0.0	0.0	Pancreatic ca.	0.0	0.0
			CAPAN2
Renal ca. UO-31	1.3	4.4	Pancreas Pool	2.8	11.0

[0883]

TABLE ZG
HASS_Panel_v1.0
	Rel.		Rel.
	Exp.(%)		Exp.(%)
	Ag817,		Ag817,
	Run		Run
Tissue Name	248122701	Tissue Name	248122701
MCF-7 C1	0.0	U87-MG F1 (B)	3.3
MCF-7 C2	0.0	U87-MG F2	1.7
MCF-7 C3	0.2	U87-MG F3	3.9
MCF-7 C4	0.1	U87-MG F4	3.5
MCF-7 C5	0.2	U87-MG F5	17.6
MCF-7 C6	0.0	U87-MG F6	51.8
MCF-7 C7	0.1	U87-MG F7	11.3
MCF-7 C9	0.0	U87-MG F8	31.6
MCF-7 C10	0.0	U87-MG F9	16.7
MCF-7 C11	0.0	U87-MG F10	8.4
MCF-7 C12	0.0	U87-MG F11	34.9
MCF-7 C13	0.1	U87-MG F12	16.8
MCF-7 C15	0.0	U87-MG F13	13.7
MCF-7 C16	0.3	U87-MG F14	44.1
MCF-7 C17	0.1	U87-MG F15	26.6
T24 D1	0.0	U87-MG F16	28.3
T24 D2	0.0	U87-MG F17	25.7
T24 D3	0.0	LnCAP A1	0.4
T24 D4	0.0	LnCAP A2	0.2
T24 D5	0.0	LnCAP A3	1.4
T24 D6	0.0	LnCAP A4	0.5
T24 D7	0.0	LnCAP A5	1.1
T24 D9	0.0	LnCAP A6	0.5
T24 D10	0.0	LnCAP A7	0.8
T24 D11	0.0	LnCAP A8	2.5
T24 D12	0.0	LnCAP A9	1.6
T24 D13	0.0	LnCAP A10	0.2
T24 D15	0.0	LnCAP A11	1.0
T24 D16	0.0	LnCAP A12	0.1
T24 D17	0.0	LnCAP A13	0.1
CAPaN B1	0.0	LnCAP A14	0.2
CAPaN B2	0.0	LnCAP A15	0.2
CAPaN B3	0.0	LnCAP A16	1.5
CAPaN B4	0.0	LnCAP A17	0.7
CAPaN B5	0.0	Primary Astrocytes	1.1
CAPaN B6	0.0	Primary Renal Proximal	1.6
		Tubule Epithelial cell A2
CAPaN B7	0.0	Primary melanocytes A5	100.0
CAPaN B8	0.0	126443 - 341 medullo	0.1
CAPaN B9	0.0	126444 - 487 medullo	0.9
CAPaN B10	0.0	126445 - 425 medullo	0.0
CAPaN B11	0.0	126446 - 690 medullo	0.1
CAPaN B12	0.0	126447 - 54 adult glioma	0.6
CAPaN B13	0.0	126448 - 245 adult	38.7
		glioma
CAPaN B14	0.0	126449 - 317 adult	0.2
		glioma
CAPaN B15	0.0	126450 - 212 glioma	62.9
CAPaN B16	0.0	126451 - 456 glioma	0.6
CAPaN B17	0.0

[0884]

TABLE ZH
Panel 1.2
	Rel.	Rel.		Rel.	Rel.
	Exp. (%)	Exp. (%)		Exp. (%)	Exp. (%)
	Ag817,	Ag817,		Ag817,	Ag817,
	Run	Run		Run	Run
Tissue Name	118348964	121027514	Tissue Name	118348964	121027514
Endothelial cells	0.0	0.0	Renal ca. 786-0	0.0	0.0
Heart (Fetal)	6.3	13.1	Renal ca. A498	4.2	2.9
Pancreas	6.4	6.6	Renal ca. RXF 393	0.7	0.5
Pancreatic ca.	0.0	0.0	Renal ca. ACHN	0.0	0.0
CAPAN 2
Adrenal Gland	6.3	7.4	Renal ca. UO-31	1.4	2.8
Thyroid	21.0	19.8	Renal ca. TK-10	0.0	0.0
Salivary gland	8.0	8.7	Liver	4.3	5.0
Pituitary gland	5.3	5.2	Liver (fetal)	2.5	1.4
Brain (fetal)	0.9	0.6	Liver ca.	0.0	0.0
			(hepatoblast) HepG2
Brain (whole)	3.7	2.8	Lung	20.6	14.5
Brain (amygdala)	2.3	3.6	Lung (fetal)	4.7	3.1
Brain (cerebellum)	0.4	0.7	Lung ca. (small cell)	0.0	0.0
			LX-1
Brain (hippocampus)	3.2	2.5	Lung ca. (small cell)	0.1	0.0
			NCI-H69
Brain (thalamus)	1.5	1.1	Lung ca. (s.cell var.)	0.0	0.0
			SHP-77
Cerebral Cortex	3.0	2.3	Lung ca. (large	0.0	0.0
			cell)NCI-H460
Spinal cord	9.5	6.2	Lung ca. (non-sm.	0.0	0.0
			cell) A549
glio/astro U87-MG	18.2	15.1	Lung ca. (non-s.cell)	0.0	0.0
			NCI-H23
glio/astro U-118-MG	9.9	6.7	Lung ca. (non-s.cell)	1.3	2.0
			HOP-62
astrocytoma	0.2	0.2	Lung ca. (non-s.cl)	0.0	0.0
SW1783			NCI-H522
neuro*; met	0.6	0.6	Lung ca. (squam.)	6.9	6.7
SK-N-AS			SW 900
astrocytoma SF-539	33.4	25.2	Lung ca. (squam.)	0.1	0.0
			NCI-H596
astrocytoma SNB-75	3.6	0.5	Mammary gland	31.4	32.1
glioma SNB-19	1.6	1.2	Breast ca.* (pl.ef)	0.0	0.0
			MCF-7
glioma U251	3.3	4.0	Breast ca.* (pl.ef)	0.0	0.0
			MDA-MB-231
glioma SF-295	8.9	10.7	Breast ca.* (pl. ef)	3.9	2.9
			T47D
Heart	54.0	67.4	Breast ca. BT-549	2.0	1.0
Skeletal Muscle	12.0	10.2	Breast ca. MDA-N	41.8	33.2
Bone marrow	0.5	0.7	Ovary	17.3	19.5
Thymus	6.7	7.0	Ovarian ca.	5.6	2.8
			OVCAR-3
Spleen	4.4	4.0	Ovarian ca.	7.5	8.7
			OVCAR-4
Lymph node	23.8	17.8	Ovarian ca.	0.3	0.2
			OVCAR-5
Colorectal Tissue	8.2	5.0	Ovarian ca.	0.2	0.2
			OVCAR-8
Stomach	10.5	9.3	Ovarian ca.	0.1	0.0
			IGROV-1
Small intestine	17.2	10.6	Ovarian ca. (ascites)	0.0	0.0
			SK-OV-3
Colon ca. SW480	0.0	0.0	Uterus	30.8	28.1
Colon ca.* SW620	0.0	0.0	Placenta	100.0	100.0
(SW480 met)
Colon ca. HT29	0.0	0.0	Prostate	5.2	4.6
Colon ca. HCT-116	0.0	0.0	Prostate ca.* (bone	0.0	0.0
			met) PC-3
Colon ca. CaCo-2	0.0	0.0	Testis	5.9	7.3
Colon ca. Tissue	4.7	3.0	Melanoma	7.2	7.5
(ODO3866)			Hs688(A).T
Colon ca. HCC-2998	0.1	0.0	Melanoma* (met)	8.7	8.5
			Hs688(B).T
Gastric ca.* (liver	20.9	17.4	Melanoma	66.9	78.5
met) NCI-N87			UACC-62
Bladder	34.2	36.6	Melanoma M14	29.9	36.6
Trachea	8.8	9.7	Melanoma LOX	0.1	0.2
			IMVI
Kidney	7.5	6.1	Melanoma* (met)	47.6	39.0
			SK-MEL-5
Kidney (fetal)	4.7	6.2

[0885]

TABLE ZI
Panel 2.2
	Rel.	Rel.		Rel.	Rel.
	Exp. (%)	Exp. (%)		Exp. (%)	Exp. (%)
	Ag817,	Ag817,		Ag817,	Ag817,
	Run	Run		Run	Run
Tissue Name	176283476	184372254	Tissue Name	176283476	184372254
Normal Colon	18.0	9.3	Kidney Margin	8.8	2.2
			(OD04348)
Colon cancer	39.8	26.1	Kidney malignant	0.6	0.6
(OD06064)			cancer
			(OD06204B)
Colon Margin	18.7	0.0	Kidney normal	4.9	4.9
(OD06064)			adjacent tissue
			(OD06204E)
Colon cancer	1.5	2.6	Kidney Cancer	48.6	40.6
(OD06159)			(OD04450-01)
Colon Margin	15.3	13.5	Kidney Margin	4.1	8.0
(OD06159)			(OD04450-03)
Colon cancer	2.8	2.6	Kidney Cancer	1.4	4.4
(OD06297-04)			8120613
Colon Margin	16.5	9.3	Kidney Margin	2.4	1.1
(OD06297-05)			8120614
CC Gr.2 ascend colon	2.6	3.6	Kidney Cancer	21.9	21.8
(ODO3921)			9010320
CC Margin	2.5	2.3	Kidney Margin	6.7	1.0
(ODO3921)			9010321
Colon cancer	5.6	9.2	Kidney Cancer	30.4	33.9
metastasis			8120607
(OD06104)
Lung Margin	7.3	9.7	Kidney Margin	0.7	1.2
(OD06104)			8120608
Colon mets to lung	15.1	10.2	Normal Uterus	59.5	42.0
(OD04451-01)
Lung Margin	56.3	12.5	Uterine Cancer	3.2	8.8
(OD04451-02)			064011
Normal Prostate	1.8	7.9	Normal Thyroid	1.1	7.2
Prostate Cancer	1.1	3.9	Thyroid Cancer	7.6	17.4
(OD04410)			064010
Prostate Margin	0.7	1.8	Thyroid Cancer	9.0	15.0
(OD04410)			A302152
Normal Ovary	13.5	14.8	Thyroid Margin	2.4	7.3
			A302153
Ovarian cancer	16.8	19.8	Normal Breast	27.9	17.9
(OD06283-03)
Ovarian Margin	10.0	4.9	Breast Cancer	7.9	10.4
(OD06283-07)			(OD04566)
Ovarian Cancer	4.0	8.7	Breast Cancer 1024	12.0	18.0
064008
Ovarian cancer	2.9	4.9	Breast Cancer	20.0	0.0
(OD06145)			(OD04590-01)
Ovarian Margin	4.4	3.9	Breast Cancer Mets	12.2	17.3
(OD06145)			(OD04590-03)
Ovarian cancer	1.8	1.4	Breast Cancer	2.7	3.6
(OD06455-03)			Metastasis
			(OD04655-05)
Ovarian Margin	11.0	0.0	Breast Cancer	10.7	17.6
(OD06455-07)			064006
Normal Lung	25.3	28.1	Breast Cancer	8.6	13.3
			9100266
Invasive poor diff.	33.2	26.2	Breast Margin	22.7	15.1
lung adeno			9100265
(ODO4945-01)
Lung Margin	13.4	9.8	Breast Cancer	3.3	6.3
(ODO4945-03)			A209073
Lung Malignant	23.7	19.3	Breast Margin	3.8	7.9
Cancer (OD03126)			A2090734
Lung Margin	5.7	34.6	Breast cancer	30.6	17.9
(OD03126)			(OD06083)
Lung Cancer	15.0	40.1	Breast cancer node	33.0	42.0
(OD05014A)			metastasis
			(OD06083)
Lung Margin	100.0	80.1	Normal Liver	2.3	2.3
(OD05014B)
Lung cancer	6.6	7.0	Liver Cancer 1026	5.0	7.4
(OD06081)
Lung Margin	5.4	3.4	Liver Cancer 1025	3.8	3.3
(OD06081)
Lung Cancer	5.5	6.8	Liver Cancer	7.5	2.4
(OD04237-01)			6004-T
Lung Margin	23.3	18.2	Liver Tissue	3.6	5.1
(OD04237-02)			6004-N
Ocular Melanoma	33.4	60.3	Liver Cancer	11.0	9.7
Metastasis			6005-T
Ocular Melanoma	3.4	5.3	Liver Tissue	16.3	8.9
Margin (Liver)			6005-N
Melanoma Metastasis	31.2	28.9	Liver Cancer	4.6	2.9
			064003
Melanoma Margin	22.2	17.0	Normal Bladder	5.6	10.3
(Lung)
Normal Kidney	1.7	3.1	Bladder Cancer	4.5	6.0
			1023
Kidney Ca, Nuclear	5.3	4.4	Bladder Cancer	22.4	30.8
grade 2 (OD04338)			A302173
Kidney Margin	22.7	84.1	Normal Stomach	9.7	10.6
(OD04338)
Kidney Ca Nuclear	92.7	100.0	Gastric Cancer	4.3	15.5
grade 1/2 (OD04339)			9060397
Kidney Margin	4.4	2.5	Stomach Margin	3.1	4.5
(OD04339)			9060396
Kidney Ca, Clear cell	5.6	11.5	Gastric Cancer	10.1	12.4
type (OD04340)			9060395
Kidney Margin	3.3	2.4	Stomach Margin	20.0	20.3
(OD04340)			9060394
Kidney Ca, Nuclear	5.4	8.6	Gastric Cancer	4.0	7.5
grade 3 (OD04348)			064005

[0886]

TABLE ZJ
Panel 2D
			Rel.
	Rel.		Exp.(%)
	xp.(%) Ag817,		Ag817,
	Run		Run
Tissue Name	150811736	Tissue Name	150811736
Normal Colon	18.9	Kidney Margin 8120608	1.2
CC Well to Mod Diff (ODO3866)	8.6	Kidney Cancer 8120613	9.2
CC Margin (ODO3866)	3.1	Kidney Margin 8120614	1.7
CC Gr.2 rectosigmoid (ODO3868)	2.1	Kidney Cancer 9010320	26.6
CC Margin (ODO3868)	0.7	Kidney Margin 9010321	1.9
CC Mod Diff (ODO3920)	0.7	Normal Uterus	8.3
CC Margin (ODO3920)	2.5	Uterus Cancer 064011	9.9
CC Gr.2 ascend colon (ODO3921)	11.9	Normal Thyroid	5.4
CC Margin (ODO3921)	2.2	Thyroid Cancer 064010	24.0
CC from Partial Hepatectomy	33.0	Thyroid Cancer A302152	7.1
(ODO4309) Mets
Liver Margin (ODO4309)	9.2	Thyroid Margin A302153	8.3
Colon mets to lung (OD04451-01)	10.4	Normal Breast	12.5
Lung Margin (OD04451-02)	11.2	Breast Cancer (OD04566)	12.9
Normal Prostate 6546-1	2.8	Breast Cancer (OD04590-01)	16.7
Prostate Cancer (OD04410)	8.7	Breast Cancer Mets	22.8
		(OD04590-03)
Prostate Margin (OD04410)	2.4	Breast Cancer Metastasis	4.4
		(OD04655-05)
Prostate Cancer (OD04720-01)	10.7	Breast Cancer 064006	19.2
Prostate Margin (OD04720-02)	19.6	Breast Cancer 1024	15.5
Normal Lung 061010	66.4	Breast Cancer 9100266	9.7
Lung Met to Muscle (ODO4286)	14.7	Breast Margin 9100265	12.8
Muscle Margin (ODO4286)	10.4	Breast Cancer A209073	14.9
Lung Malignant Cancer (OD03126)	45.7	Breast Margin A209073	6.0
Lung Margin (OD03126)	34.6	Normal Liver	1.1
Lung Cancer (OD04404)	100.0	Liver Cancer 064003	4.0
Lung Margin (OD04404)	13.7	Liver Cancer 1025	1.5
Lung Cancer (OD04565)	50.0	Liver Cancer 1026	7.8
Lung Margin (OD04565)	12.7	Liver Cancer 6004-T	2.0
Lung Cancer (OD04237-01)	29.5	Liver Tissue 6004-N	10.8
Lung Margin (OD04237-02)	17.3	Liver Cancer 6005-T	7.8
Ocular Mel Met to Liver	56.3	Liver Tissue 6005-N	2.5
(ODO4310)
Liver Margin (ODO4310)	3.8	Normal Bladder	16.4
Melanoma Mets to Lung (OD04321)	58.2	Bladder Cancer 1023	7.4
Lung Margin (OD04321)	18.7	Bladder Cancer A302173	33.0
Normal Kidney	10.0	Bladder Cancer (OD04718-01)	8.6
Kidney Ca, Nuclear grade 2	79.0	Bladder Normal Adjacent	7.9
(OD04338)		(OD04718-03)
Kidney Margin (OD04338)	3.1	Normal Ovary	9.7
Kidney Ca Nuclear grade 1/2	80.1	Ovarian Cancer 064008	21.0
(OD04339)
Kidney Margin (OD04339)	4.2	Ovarian Cancer (OD04768-07)	15.1
Kidney Ca, Clear cell type	22.8	Ovary Margin (OD04768-08)	4.7
(OD04340)
Kidney Margin (OD04340)	6.7	Normal Stomach	7.4
Kidney Ca, Nuclear grade 3	7.5	Gastric Cancer 9060358	6.5
(OD04348)
Kidney Margin (OD04348)	2.4	Stomach Margin 9060359	4.5
Kidney Cancer (OD04622-01)	49.0	Gastric Cancer 9060395	17.3
Kidney Margin (OD04622-03)	1.0	Stomach Margin 9060394	11.4
Kidney Cancer (OD04450-01)	32.5	Gastric Cancer 9060397	25.5
Kidney Margin (OD04450-03)	4.2	Stomach Margin 9060396	2.2
Kidney Cancer 8120607	21.8	Gastric Cancer 064005	9.9

[0887]

TABLE ZK
Panel 3D
	Rel.		Rel.
	Exp (%)		Exp.(%)
	Ag817,		Ag817,
	Run		Run
Tissue Name	164729916	Tissue Name	164729916
Daoy-Medulloblastoma	1.1	Ca Ski-Cervical epidermoid	0.2
		carcinoma (metastasis)
TE671-Medulloblastoma	0.3	ES-2-Ovarian clear cell carcinoma	0.4
D283 Med-Medulloblastoma	0.8	Ramos-Stimulated with	0.0
		PMA/ionomycin 6 h
PFSK-1-Primitive	0.8	Ramos-Stimulated with	0.0
Neuroectodermal		PMA/ionomycin 14 h
XF-498-CNS	65.5	MEG-01-Chronic myelogenous	0.0
		leukemia (megokaryoblast)
SNB-78-Glioma	17.9	Raji-Burkitt's lymphoma	0.0
SF-268-Glioblastoma	0.5	Daudi-Burkitt's lymphoma	0.0
T98G-Glioblastoma	1.5	U266-B-cell plasmacytoma	0.1
SK-N-SH-Neuroblastoma	0.6	CA46-Burkitt's lymphoma	0.0
(metastasis)
SF-295-Glioblastoma	3.7	RL-non-Hodgkin's B-cell	0.0
		lymphoma
Cerebellum	0.7	JM1-pre-B-cell lymphoma	0.0
Cerebellum	0.4	Jurkat-T cell leukemia	0.0
NCI-H292-Mucoepidermoid	0.0	TF-1-Erythroleukemia	0.0
lung carcinoma
DMS-114-Small cell lung	1.7	HUT 78-T-cell lymphoma	0.0
cancer
DMS-79-Small cell lung cancer	0.5	U937-Histiocytic lymphoma	12.4
NCI-H146-Small cell lung	0.0	KU-812-Myelogenous leukemia	0.0
cancer
NCI-H526-Small cell lung	0.0	769-P-Clear cell renal carcinoma	0.0
cancer
NCI-N417-Small cell lung	0.0	Caki-2-Clear cell renal carcinoma	4.0
cancer
NCI-H82-Small cell lung cancer	0.0	SW 839-Clear cell renal carcinoma	1.9
NCI-H157-Squamous cell lung	0.0	Rhabdoid kidney tumor	1.9
cancer (metastasis)
NCI-H1155-Large cell lung	0.0	Hs766T-Pancreatic carcinoma (LN	0.4
cancer		metastasis)
NCI-H1299-Large cell lung	0.0	CAPAN-1-Pancreatic	0.2
cancer		adenocarcinoma (liver metastasis)
NCI-H727-Lung carcinoid	0.0	SU86.86-Pancreatic carcinoma	0.1
		(liver metastasis)
NCI-UMC-11-Lung carcinoid	0.0	BxPC-3-Pancreatic	0.2
		adenocarcinoma
LX-1-Small cell lung cancer	0.0	HPAC-Pancreatic adenocarcinoma	0.0
Colo-205-Colon cancer	0.0	MIA PaCa-2-Pancreatic carcinoma	0.0
KM12-Colon cancer	0.0	CFPAC-1-Pancreatic ductal	0.0
		adenocarcinoma
KM20L2-Colon cancer	0.0	PANC-1-Pancreatic epithelioid	0.0
		ductal carcinoma
NCI-H716-Colon cancer	0.0	T24-Bladder carcinma (transitional	0.0
		cell)
SW-48-Colon adenocarcinoma	0.0	5637-Bladder carcinoma	0.0
SW1116-Colon adenocarcinoma	0.0	HT-1197-Bladder carcinoma	0.7
LS 174T-Colon adenocarcinoma	0.0	UM-UC-3-Bladder carcinma	0.0
		(transitional cell)
SW-948-Colon adenocarcinoma	0.0	A204-Rhabdomyosarcoma	0.0
SW-480-Colon adenocarcinoma	0.0	HT-1080-Fibrosarcoma	0.6
NCI-SNU-5-Gastric carcinoma	0.0	MG-63-Osteosarcoma	4.7
KATO III-Gastric carcinoma	0.0	SK-LMS-1-Leiomyosarcoma	5.4
		(vulva)
NCI-SNU-16-Gastric carcinoma	8.4	SJRH30-Rhabdomyosarcoma (met	0.0
		to bone marrow)
NCI-SNU-1-Gastric carcinoma	0.0	A431-Epidermoid carcinoma	1.0
RF-1-Gastric adenocarcinoma	0.0	WM266-4-Melanoma	100.0
RF-48-Gastric adenocarcinoma	0.0	DU 145-Prostate carcinoma (brain	0.0
		metastasis)
MKN-45-Gastric carcinoma	0.0	MDA-MB-468-Breast	0.4
		adenocarcinoma
NCI-N87-Gastric carcinoma	0.1	SCC-4-Squamous cell carcinoma	0.0
		of tongue
OVCAR-5-Ovarian carcinoma	0.0	SCC-9-Squamous cell carcinoma	0.0
		of tongue
RL95-2-Uterine carcinoma	5.4	SCC-15-Squamous cell carcinoma	0.0
		of tongue
HelaS3-Cervical	0.0	CAL 27-Squamous cell carcinoma	0.2
adenocarcinoma		of tongue

[0888]

TABLE ZL
Panel 4.1D
	Rel.	Rel.		Rel.	Rel.
	Exp. (%)	Exp. (%)		Exp. (%)	Exp. (%)
	Ag5968,	Ag817,		Ag5968,	Ag817,
	Run	Run		Run	Run
Tissue Name	248173663	247683512	Tissue Name	248173663	247683512
Secondary Th1 act	0.0	0.0	HUVEC IL-1beta	0.0	0.0
Secondary Th2 act	0.0	0.0	HUVEC IFN gamma	0.0	0.0
Secondary Tr1 act	0.0	0.0	HUVEC TNF alpha +	0.0	0.0
			IFN gamma
Secondary Th1 rest	0.0	0.0	HUVEC TNF alpha +	0.0	0.2
			IL4
Secondary Th2 rest	0.0	0.0	HUVEC IL-11	0.0	0.0
Secondary Tr1 rest	0.0	0.0	Lung Microvascular	0.1	0.3
			EC none
Primary Th1 act	0.0	0.0	Lung Microvascular	0.0	0.0
			EC TNF alpha +
			IL-1beta
Primary Th2 act	0.0	0.0	Microvascular	0.0	0.0
			Dermal EC none
Primary Tr1 act	0.0	0.0	Microsvasular	0.0	0.0
			Dermal EC
			TNF alpha + IL-1beta
Primary Th1 rest	0.0	0.0	Bronchial epithelium	3.2	3.6
			TNF alpha + IL1beta
Primary Th2 rest	0.0	0.0	Small airway	1.1	2.5
			epithelium none
Primary Tr1 rest	0.0	0.0	Small airway	1.1	1.8
			epithelium TNF
			alpha + IL-1beta
CD45RA CD4	0.4	0.5	Coronery artery SMC	0.2	0.6
lymphocyte act			rest
CD45RO CD4	0.0	0.0	Coronery artery SMC	0.6	1.0
lymphocyte act			TNF alpha + IL-1beta
CD8 lymphocyte act	0.0	0.0	Astrocytes rest	0.0	0.0
Secondary CD8	0.0	0.0	Astrocytes TNF	0.0	0.0
lymphocyte rest			alpha + IL-1beta
Secondary CD8	0.0	0.0	KU-812 (Basophil)	0.0	0.0
lymphocyte act			rest
CD4 lymphocyte none	0.0	0.0	KU-812 (Basophil)	0.0	0.0
			PMA/ionomycin
2ry	0.0	0.0	CCD1106	0.9	0.9
Th1/Th2/Tr1_anti-CD95			(Keratinocytes) none
CH11
LAK cells rest	29.7	17.4	CCD1106	0.4	0.7
			(Keratinocytes)
			TNF alpha + IL-1beta
LAK cells IL-2	0.0	0.0	Liver cirrhosis	1.9	2.4
LAK cells IL-2 + IL-12	0.0	0.1	NCI-H292 none	0.0	0.1
LAK cells IL-2 + IFN	0.2	0.2	NCI-H292 IL-4	0.0	0.1
gamma
LAK cells IL-2 + IL-18	0.3	0.1	NCI-H292 IL-9	0.1	0.1
LAK cells	63.3	36.3	NCI-H292 IL-13	0.0	0.2
PMA/ionomycin
NK Cells IL-2 rest	0.0	0.0	NCI-H292 IFN	0.0	0.1
			gamma
Two Way MLR 3 day	3.2	1.4	HPAEC none	0.0	0.0
Two Way MLR 5 day	1.0	0.3	HPAEC TNF alpha +	0.0	0.1
			IL-1beta
Two Way MLR 7 day	0.1	0.1	Lung fibroblast none	4.3	8.7
PBMC rest	0.0	0.0	Lung fibroblast TNF	1.7	2.0
			alpha + IL-1beta
PBMC PWM	0.0	0.0	Lung fibroblast IL-4	1.2	2.6
PBMC PHA-L	0.0	0.0	Lung fibroblast IL-9	3.1	2.2
Ramos (B cell) none	0.0	0.0	Lung fibroblast IL-13	1.4	1.6
Ramos (B cell)	0.0	0.0	Lung fibroblast IFN	4.8	5.3
ionomycin			gamma
B lymphocytes PWM	0.0	0.0	Dermal fibroblast	1.5	3.3
			CCD1070 rest
B lymphocytes CD40L	0.1	0.0	Dermal fibroblast	1.4	2.1
and IL-4			CCD1070 TNF alpha
EOL-1 dbcAMP	0.0	0.0	Dermal fibroblast	1.0	1.3
			CCD1070 IL-1beta
EOL-1 dbcAMP	0.0	0.0	Dermal fibroblast	19.5	17.0
PMA/ionomycin			IFN gamma
Dendritic cells none	100.0	70.2	Dermal fibroblast	48.6	25.3
			IL-4
Dendritic cells LPS	19.8	14.3	Dermal Fibroblasts	76.3	19.5
			rest
Dendritic cells	18.8	24.8	Neutrophils	0.0	0.0
anti-CD40			TNFa + LPS
Monocytes rest	0.0	0.0	Neutrophils rest	0.0	0.0
Monocytes LPS	17.9	19.2	Colon	0.1	0.1
Macrophages rest	26.8	19.5	Lung	1.9	1.0
Macrophages LPS	5.2	100.0	Thymus	1.2	0.5
HUVEC none	0.0	0.0	Kidney	1.4	0.7
HUVEC starved	0.0	0.0

[0889]

TABLE ZM
Panel 4D
	Rel.	Rel.		Rel.	Rel.
	Exp. (%)	Exp. (%)		Exp. (%)	Exp. (%)
	Ag817,	Ag817,		Ag817,	Ag817,
	Run	Run		Run	Run
Tissue Name	139579600	139892411	Tissue Name	139579600	139892411
Secondary Th1 act	0.0	0.0	HUVEC IL-1beta	0.0	0.0
Secondary Th2 act	0.0	0.0	HUVEC IFN gamma	0.0	0.0
Secondary Tr1 act	0.0	0.0	HUVEC TNF alpha +	0.0	0.0
			IFN gamma
Secondary Th1 rest	0.0	0.0	HUVEC TNF alpha +	0.0	0.0
			IL4
Secondary Th2 rest	0.0	0.0	HUVEC IL-11	0.0	0.0
Secondary Tr1 rest	0.0	0.0	Lung Microvascular	0.0	0.0
			EC none
Primary Th1 act	0.0	0.0	Lung Microvascular	0.0	0.0
			EC TNF alpha +
			IL-1beta
Primary Th2 act	0.0	0.0	Microvascular	0.0	0.0
			Dermal EC none
Primary Tr1 act	0.0	0.0	Microvasular	0.0	0.0
			Dermal EC
			TNF alpha + IL-1beta
Primary Th1 rest	0.0	0.0	Bronchial epithelium	8.0	11.6
			TNF alpha + IL1beta
Primary Th2 rest	0.0	0.0	Small airway	1.4	1.1
			epithelium none
Primary Tr1 rest	0.0	0.0	Small airway	2.0	2.3
			epithelium TNF alpha +
			IL-1beta
CD45RA CD4	0.3	0.3	Coronery artery SMC	0.3	0.4
lymphocyte act			rest
CD45RO CD4	0.0	0.0	Coronery artery SMC	0.5	0.7
lymphocyte act			TNF alpha + IL-1beta
CD8 lymphocyte act	0.0	0.0	Astrocytes rest	0.0	0.0
Secondary CD8	0.0	0.0	Astrocytes TNF alpha +	0.0	0.0
lymphocyte rest			IL-1beta
Secondary CD8	0.0	0.0	KU-812 (Basophil)	0.0	0.0
lymphocyte act			rest
CD4 lymphocyte none	0.0	0.0	KU-812 (Basophil)	0.0	0.0
			PMA/ionomycin
2ry	0.0	0.0	CCD1106	0.4	0.7
Th1/Th2/Tr1_anti-CD95			(Keratinocytes) none
CH11
LAK cells rest	32.3	39.5	CCD1106	3.8	4.6
			(Keratinocytes)
			TNF alpha + IL-1beta
LAK cells IL-2	0.0	0.0	Liver cirrhosis	0.6	1.4
LAK cells IL-2 + IL-12	0.3	0.4	Lupus kidney	0.6	0.9
LAK cells IL-2 + IFN	0.4	0.6	NCI-H292 none	0.1	0.1
gamma
LAK cells IL-2 + IL-18	0.3	0.3	NCI-H292 IL-4	0.1	0.1
LAK cells	23.3	33.2	NCI-H292 IL-9	0.1	0.1
PMA/ionomycin
NK Cells IL-2 rest	0.0	0.0	NCI-H292 IL-13	0.0	0.1
Two Way MLR 3 day	1.2	1.9	NCI-H292 IFN	0.0	0.0
			gamma
Two Way MLR 5 day	0.8	1.1	HPAEC none	0.0	0.0
Two Way MLR 7 day	0.3	0.4	HPAEC TNF alpha +	0.0	0.0
			IL-1beta
PBMC rest	0.0	0.0	Lung fibroblast none	1.6	2.8
PBMC PWM	0.0	0.0	Lung fibroblast TNF	0.4	0.7
			alpha + IL-1beta
PBMC PHA-L	0.1	0.2	Lung fibroblast IL-4	1.8	2.8
Ramos (B cell) none	0.0	0.0	Lung fibroblast IL-9	1.0	1.8
Ramos (B cell)	0.0	0.0	Lung fibroblast IL-13	3.4	4.8
ionomycin
B lymphocytes PWM	0.0	0.0	Lung fibroblast IFN	2.9	3.7
			gamma
B lymphocytes CD40L	0.0	0.0	Dermal fibroblast	1.5	2.0
and IL-4			CCD1070 rest
EOL-1 dbcAMP	0.0	0.0	Dermal fibroblast	0.9	1.5
			CCD1070 TNF alpha
EOL-1 dbcAMP	0.0	0.0	Dermal fibroblast	0.8	1.1
PMA/ionomycin			CCD1070 IL-1beta
Dendritic cells none	39.0	51.8	Dermal fibroblast	8.1	9.4
			IFN gamma
Dendritic cells LPS	15.2	18.7	Dermal fibroblast	19.3	27.7
			IL-4
Dendritic cells	33.4	44.1	IBD Colitis 2	0.1	0.2
anti-CD40
Monocytes rest	0.0	0.0	IBD Crohn's	0.3	0.5
Monocytes LPS	11.6	16.7	Colon	1.2	1.6
Macrophages rest	100.0	100.0	Lung	8.7	12.0
Macrophages LPS	39.0	40.3	Thymus	2.2	3.3
HUVEC none	0.0	0.0	Kidney	3.8	4.6
HUVEC starved	0.0	0.0

[0890]

TABLE ZN
Panel 4R
	Rel.		Rel.
	Ex.(%)		Exp.(%)
	Ag817,		Ag817,
	Run		Run
Tissue Name	140125854	Tissue Name	140125854
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 +	0.0
		IL-1beta
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 +	13.9
		IL1beta
Primary Th2 rest	0.0	Small airway epithelium none	0.4
Primary Tr1 rest	0.0	Small airway epithelium TNF alpha +	8.5
		IL-1beta
CD45RA CD4 lymphocyte act	0.8	Coronery artery SMC rest	0.8
CD45RO CD4 lymphocyte act	0.0	Coronery artery SMC TNF alpha +	2.4
		IL-1beta
CD8 lymphocyte act	0.0	Astrocytes rest	0.0
Secondary CD8 lymphocyte rest	0.0	Astrocytes TNF alpha + IL-1beta	0.3
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	1.6
CH11
LAK cells rest	55.9	CCD1106 (Keratinocytes)	24.1
		TNF alpha + IL-1beta	24.1
LAK cells IL-2	0.0	Liver cirrhosis	4.0
LAK cells IL-2 + IL-12	0.9	Lupus kidney	2.2
LAK cells IL-2 + IFN gamma	1.2	NCI-H292 none	0.6
LAK cells IL-2 + IL-18	1.1	NCI-H292 IL-4	0.9
LAK cells PMA/ionomycin	58.6	NCI-H292 IL-9	0.7
NK Cells IL-2 rest	0.0	NCI-H292 IL-13	0.2
Two Way MLR 3 day	3.3	NCI-H292 IFN gamma	0.1
Two Way MLR 5 day	1.7	HPAEC none	0.1
Two Way MLR 7 day	1.2	HPAEC TNF alpha + IL-1beta	0.0
PBMC rest	0.1	Lung fibroblast none	10.4
PBMC PWM	0.0	Lung fibroblast TNF alpha + IL-1	1.6
		beta
PBMC PHA-L	0.3	Lung fibroblast IL-4	3.1
Ramos (B cell) none	0.0	Lung fibroblast IL-9	2.9
Ramos (B cell) ionomycin	0.0	Lung fibroblast IL-13	1.6
B lymphocytes PWM	0.1	Lung fibroblast IFN gamma	3.0
B lymphocytes CD40L and IL-4	0.2	Dermal fibroblast CCD1070 rest	4.7
EOL-1 dbcAMP	0.0	Dermal fibroblast CCD1070 TNF	5.1
		alpha
EOL-1 dbcAMP	0.1	Dermal fibroblast CCD1070 IL-1	1.6
PMA/ionomycin		beta
Dendritic cells none	95.3	Dermal fibroblast IFN gamma	43.8
Dendritic cells LPS	35.4	Dermal fibroblast IL-4	28.5
Dendritic cells anti-CD40	68.3	IBD Colitis 1	2.3
Monocytes rest	0.0	IBD Colitis 2	0.2
Monocytes LPS	30.8	IBD Crohn's	1.8
Macrophages rest	100.0	Colon	5.5
Macrophages LPS	87.1	Lung	48.3
HUVEC none	0.0	Thymus	4.3
HUVEC starved	0.0	Kidney	23.3

[0891]

TABLE ZO
general_oncology_screening_panel_v 2.4
	Rel.	Rel.	Rel.		Rel.	Rel.	Rel.
	Exp. (%)	Exp. (%)	Exp. (%)		Exp. (%)	Exp. (%)	Exp. (%)
	Ag817,	Ag817,	Ag817,		Ag817,	Ag817,	Ag817,
	Run	Run	Run		Run	Run	Run
Tissue Name	258052110	258680989	259733170	issue Name	258052110	258680989	259733170
Colon cancer 1	5.0	6.6	6.2	Bladder cancer	1.0	0.9	0.9
				NAT 2
Colon cancer	2.6	2.1	2.4	Bladder cancer	0.3	0.3	0.2
NAT 1				NAT 3
Colon cancer 2	25.5	23.2	26.6	Bladder cancer	9.1	7.9	6.3
				NAT 4
Colon cancer	5.6	4.3	4.4	Prostate	10.0	8.6	8.8
NAT 2				adenocarcinoma 1
Colon cancer 3	14.2	14.6	10.6	Prostate	1.3	1.5	1.2
				adenocarcinoma 2
Colon cancer	7.6	7.1	6.3	Prostate	2.2	2.0	1.2
NAT 3				adenocarcinoma 3
Colon	29.1	29.7	32.1	Prostate	11.1	10.4	11.2
malignant				adenocarcinoma 4
cancer 4
Colon normal	5.1	4.4	3.5	Prostate cancer	1.3	1.5	1.2
adjacent tissue 4				NAT 5
Lung cancer 1	28.5	24.5	27.7	Prostate	1.7	1.5	1.3
				adenocarcinoma 6
Lung NAT 1	12.2	10.4	9.2	Prostate	1.6	2.0	1.3
				adenocarcinoma 7
Lung cancer 2	22.7	20.0	24.5	Prostate	0.7	0.6	0.6
				adenocarcinoma 8
Lung NAT 2	4.9	5.1	5.2	Prostate	4.0	4.1	4.3
				adenocarcinoma 9
Squamous cell	64.6	60.3	47.3	Prostate cancer	1.3	1.4	1.3
carcinoma 3				NAT 10
Lung NAT 3	4.3	3.7	6.1	Kidney cancer 1	44.1	40.3	44.1
metastatic	18.8	16.6	17.6	KidneyNAT 1	2.4	2.4	2.7
melanoma 1
Melanoma 2	20.6	19.3	17.7	Kidney cancer 2	23.2	23.0	26.4
Melanoma 3	14.8	13.5	13.0	Kidney NAT 2	4.7	4.7	5.1
metastatic	100.0	100.0	100.0	Kidney cancer 3	9.6	8.4	6.3
melanoma 4
metastatic	40.9	38.7	46.3	Kidney NAT 3	1.2	1.2	1.2
melanoma 5
Bladder cancer 1	4.9	5.3	4.4	Kidney cancer 4	5.3	3.9	5.3
Bladder cancer	0.0	0.0	0.0	Kidney NAT 4	1.1	1.0	1.1
NAT 1
Bladder cancer 2	11.3	13.5	14.2

[0892] AI_comprehensive panel_v1.0 Summary: Ag8l7 Highest expression of this gene is detected in a orthoarthritis bone (CT=24.3). This gene shows a wide spread expression profile in this panel. High to moderate expression of the gene is seen in 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). Interestingly, expression of this gene is upregulated in bone and synovium from OA patients. 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.

[0893] Ardais Panel v.1.0 Summary: Ag817 Highest expression of this gene is detected in a lung cancer (372) sample (CT=20.1). High expression of this gene is seen both in normal adjacent and cancer samples from lung. Therefore, therapeutic modulation of this gene or its protein product may be useful in the treatment of lung cancer.

[0894] CNS_neurodegeneration_v1.0 Summary: Ag5968 This panel confirms the expression of this gene at low levels in the brain in an independent group of individuals. This gene is found to be slightly upregulated in the temporal cortex of Alzheimer's disease patients. Therefore, therapeutic modulation of the expression or function of this gene may decrease neuronal death and be of use in the treatment of this disease.

[0895] General_screening_panel_v1.5 Summary: Ag817 Highest expression of this gene is detected in melanoma M14 cell line (CT=22). High expression of this gene is also seen in colon cancer and number of cell lines derived from melanoma, ovarian, breast, renal, and brain cancer. This gene codes for a putative-transmembrane protein NMB precursor (GPNMB). Using the GeneCalling study at CuraGen the mouse ortholog of GPNMB has been shown to be highly upregulated in a Neural Stem Cell (NSC) line derived from the TSC2 knockout, a model for the Tuberous Sclerosis Complex syndrome. This tumor suppressor gene is involved in the regulation of cell growth, shape and interaction with the extracellular matrix. The NSC cells are a model for the CNS phenotypes associated with TSC (giant cell astrocytoma among others). Riggins's group at Duke identified GPNMB as one of 7 most highly expressed genes in glioblastoma multiforme with specific induction in tumors (Loging W T, Lal A, Siu I M, Loney T L, Wikstrand C J, Marra M A, Prange C, Bigner D D, Strausberg R L, Riggins G J. Genome Res. September 2000; 10(9): 1393-402). Therefore, based on this and the expression profile, therapeutic modulation of this gene through the use of antibodies or small molecule may be beneficial in the treatment of melanoma, ovarian, breast, renal, and brain cancers including glioblastoma multiforme.

[0896] Among tissues with metabolic or endocrine function, this gene is expressed at high to moderate levels in pancreas, adipose, adrenal gland, thyroid, pituitary gland, skeletal muscle, heart, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene may prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0897] 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.

[0898] HASS Panel v1.0 Summary: Ag817

[0899] This gene is a target in brain cancer-specifically gliomas as it is expressed at a higher level in gliomas than medulloblastomas. It is induced by serum-starvation in U87-MG cells (wells 50 and 52) and was induced by treating serum-starved cells for 12 hrs with serum containing media (well 53). Therapeutic modulation of the expression or function of this gene may alleviate brain cancer; specifically gliomas and be of use in the treatment of this disease.

[0900] Panel 1.2 Summary: Ag817 Two experiments with same probe-primer sets are in good agreement, with highest expression of this gene seen in placenta (CTs=20.8). High to moderate expression of this gene is seen in normal tissues and number of cancer cell line. The expression correlates with expression profile seen in panel 1.5. Please see panel 1.5 for further discussion on the utility of this gene.

[0901] Panel 2.2 Summary: Ag817 Two experiments with same probe-primer sets are in good agreement. Highest expression of this gene is detected in kidney cancer and control lung sample (CTs=22-25). This gene shows widespread expression in this panel with high expression in cancer and corresponding normal adjacent tissues. Please see panel 1.5 and 2.4 for further discussion on the utility of this gene.

[0902] Panel 2D Summary: Ag817 Highest expression of this gene is detected in lung cancer sample (CT=23.7). This gene shows widespread expression in this panel with high expression in cancer and corresponding normal adjacent tissues. Please see panel 1.5 and 2.4 for further discussion on the utility of this gene.

[0903] Panel 3D Summary: Ag817 Highest expression of this gene is detected in melanoma WM266-4 cell line (CT=24.5). High to moderate expression of this gene is also detected in number of cancer cell lines derived from brain, gastric, uterine, ovarian, cervical, histiocytic lymphoma, renal, bladder, pancreatic, bone, vulva and tongue cancers. Therefore, therapeutic modulation of this gene or its protein product may be useful in the treatment of these cancers.

[0904] Panel 4.1D Summary: Ag5968/Ag817 Two experiments with different probe and primer sets are in good agreement. Highest expression of this gene is detected in resting dendritic cells and activated macrophage (CTs=25-26.5). The expression profile seen in this panel correlates with that seen in panel 4D. Please see panel 4D for further discussion on the utility of this gene.

[0905] Panel 4D Summary: Ag817 Two experiments with same probe and primer sets are in excellent agreement with highest expression of this gene seen in resting macrophage (CTs=21). High expression of this gene is mainly seen in activated monocytes, resting and activated dendritic cells, macrophages and LAK cells. Moderate to high expression of this gene is also seen in two way MLR, PHA-L activated PBMC cells, cytokine activated bronchial epithelium and coronary artery SMC, resting and activated small airway epithelium, activated astrocytes, keratinocytes, mucoepidermoid NCI-H292 cells, HPAEC, lung and dermal fibroblasts, liver cirrhosis, lupus kidney, IBD Crohn's colitis, normal tissues represented by colon, lung, thymus and kidney. Recent data published in JBC (Shikano et. al., 276(11):8125-34) demonstrated that the mouse ortholog of NMB (DC-HIL) was expressed on a mouse Dendritic cell-like line (DC are myeloid lineage cells that specialize in presentation of antigen to T cells), and proposed that it was involved in DC migration (transendothelial migration). Therefore, therapeutic modulation of this gene or its protein product through the use of antibodies or small molecule drug may be useful in the treatment of diseases in which dendritic cells and macrophages play an important role, such as, but not limited to, including Crohn's disease, ulcerative colitis, multiple sclerosis, chronic obstructive pulmonary disease, asthma, emphysema, rheumatoid arthritis, lupus erythematosus, or psoriasis.

[0906] Panel 4R Summary: Ag817 Highest expression of this gene is detected in resting macrophage (CT=24.3). The expression profile seen in this panel correlates with that seen in panel 4D. Please see panel 4D for further discussion on the utility of this gene. general oncology screening panel_v—2.4 Summary: Ag8 17 Three experiments with same probe-primer sets are in excellent agreement with highest expression of this gene seen in metastatic melanoma (CTs=22-24.8). High to moderate expression of this gene is seen in both normal adjacent and cancer samples derived from colon, prostate, lung, kidney, bladder and melanoma. Interestingly, expression of this gene is higher in cancer samples compared to the adjacent normal tissue. Therefore, expression of this gene may be used as diagnostic marker to detect the presence of melanoma, metastatic melanoma, and colon, prostate, lung, kidney, bladder cancers. Furthermore, therapeutic modulation of this gene through the use of antibodies or small molecule drug may be useful in the treatment of melanoma, metastatic melanoma, and colon, prostate, lung, kidney, bladder cancers.

Example D

[0907] Identification of Single Nucleotide Polymorphisms in NOVX Nucleic Acid Sequences

[0908] 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.

[0909] 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.

[0910] Some additional genomic regions may have also been identified because selected SeqCalling assemblies map to those regions. Such SeqCalling sequences may have overlapped with regions defined by homology or exon prediction. They may also be included because the location of the fragment was in the vicinity of genomic regions identified by similarity or exon prediction that had been included in the original predicted sequence. The sequence so identified was manually assembled and then may have been extended using one or more additional sequences taken from CuraGen Corporation's human SeqCalling database. SeqCalling fragments suitable for inclusion were identified by the CuraTools™ program SeqExtend or by identifying SeqCalling fragments mapping to the appropriate regions of the genomic clones analyzed.

[0911] 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).

[0912] 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.

	Nucleotides	Amino Acids
Variant	Position	Initial	Modified	Position	Initial	Modified
NOV 27b: SNP Variants for SLPI-like Protein CG055060-01.
13374945	38	T	C	7	Phe	Ser
13377692	53	T	C	12	Leu	Pro
13376226	169	T	C	51	Cys	Arg
13374947	173	A	G	52	Gln	Arg
13374948	188	G	A	57	Cys	Tyr
13374949	193	G	A	59	Gly	Arg
NOV 28c: SNP Variants for NMB-like Protein CG056972-01.
13375128	233	T	C	47	Trp	Arg
13375127	263	A	G	57	Lys	Glu
13375129	425	A	G	111	Asn	Asp
13381799	484	A	G	130	Pro	Pro
13375130	555	A	G	154	Asn	Ser
13375131	578	T	C	162	Phe	Leu
13375132	975	C	T	294	Ser	Phe
13375133	1065	C	T	324	Pro	Leu
13381798	1474	T	C	460	Asp	Asp
13381797	1555	T	C	487	Ser	Ser
13381796	1672	C	A	526	Ser	Arg
13381810	1832	T	C	0	—	—
13381795	1899	G	A	0	—	—
NOV 1b: SNP Variant for von Ebner's gland protein
precursor-like Protein CG102689-02.
13381709	205	T	C	62	Leu	Pro
NOV 2b: SNP Variants for Fibulin-2-like Protein CG103827-02.
13381701	3006	T	C	979	Gly	Gly
13381704	3733	T	A	0	—	—
13381705	3740	C	A	0	—	—
NOV 3g: SNP Variant for germline oligomeric matrix protein-like
Protein CG105716-01.
13378855	1304	A	G	435	Asp	Gly
NOV 4b: SNP Variants for Protein CGI-100 precursor-like
Protein CG153910-02.
13381722	462	C	A	0	—	—
13381716	825	G	T	59	Glu	End
13381715	1005	G	A	119	Val	Met
NOV 6a: SNP Variants for Type Ib membrane protein-like
Protein CG159093-01.
13381719	915	A	G	282	Arg	Gly
13381718	936	T	C	289	Ser	Pro
13381717	1069	T	C	333	Leu	Pro
NOV 9b: SNP Variant for MS4A7-like Protein CG160152-03.
13381738	408	T	A	134	Leu	End
NOV 11a: SNP Variants for Type IIIa membrane protein-like
Protein CG160244-01.
13381741	1716	A	G	532	His	Arg
13381736	3451	A	G	1110	Leu	Leu
13381742	3661	G	A	1180	Pro	Pro
13381743	4799	G	C	1560	Ala	Pro
NOV 12a: SNP Variants for Lectin C-type and SCP domains
containing extracellular protein-like Protein CG160541-01
13381753	39	T	C	0
13381752	439	A	G	126	Leu	Leu
13381751	513	C	T	151	Thr	Met
13381750	1207	T	C	382	Ala	Ala
13381748	1367	C	T	0	—	—
13381745	1560	A	G	0	—	—
13381744	1658	A	G	0	—	—
NOV 13b: SNP Variants for Soggy-1 protein precursor-like
Protein CG161630-02
13381733	159	G	A	29	Ala	Thr
13381732	399	A	G	109	Ser	Gly
13381731	480	G	A	136	Glu	Lys
NOV 15b: SNP Variants for Folate receptor beta-like
Protein CG162177-02
13381761	687	G	T	199	Ala	Ala
13381760	698	C	A	203	Ala	Asp
NOV 17a: SNP Variant for Leukocyte-associated IG-like
receptor-2-like Protein CG162509-02.
13376537	380	G	C	123	Ser	Thr
NOV 18b: SNP Variants for Cell surface receptor FDF03-dtm
precursor-like Protein CG162645-01
13381770	314	A	G	99	Tyr	Cys
13381769	458	A	G	147	Glu	Gly
13381768	527	T	C	170	Ile	Thr
NOV 19b: SNP Variant for membrane protein-like
Protein CG162687-01
13381767	163	A	G	0	—	—
NOV 21a: SNP Variants for membrane protein-like
Protein CG163175-01
13381808	217	C	T	29	Ala	Ala
13381789	742	T	C	204	Gly	Gly
13381788	760	T	C	210	Ser	Ser
13381787	796	G	A	222	Pro	Pro
13381786	803	T	C	225	Phe	Leu
13381785	826	T	G	232	Ala	Ala
NOV 22a: SNP Variants for Cytokine-like factor-1-like
Protein CG163259-01
13381803	281	T	C	55	Ser	Pro
13381812	355	C	T	79	Asn	Asn
13381814	777	G	A	220	Cys	Tyr
13381815	814	G	A	232	Gln	Gln
NOV 25a: SNP Variants for 4930418P06RIK Homolog with
Rhomboid domain-like Protein CG164482-01
13381800	319	T	C	73	Leu	Leu
13381811	392	A	G	98	Arg	Gly
13381801	503	T	C	135	Phe	Leu
NOV 26a: SNP Variant for DORA protein precursor-like
Protein CG164511-01.
13381790	740	T	C	0	—	—

Other Embodiments

[0913] 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 77.

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 77.

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 77.

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 77.

5. The polypeptide of claim 1 wherein said polypeptide is naturally occurring.

6. A composition comprising the polypeptide of claim 1 and a carrier.

7. A kit comprising, in one or more containers, the composition of claim 6.

8. The use of a therapeutic in the manufacture of a medicament for treating a syndrome associated with a human disease, the disease selected from a pathology associated with the polypeptide of claim 1, wherein the therapeutic comprises the polypeptide of claim 1.

9. A method for determining the presence or amount of the polypeptide of claim 1 in a sample, the method comprising: (a) providing said sample; (b) introducing said sample to an antibody that binds immunospecifically to the polypeptide; and (c) determining the presence or amount of antibody bound to said polypeptide, thereby determining the presence or amount of polypeptide in said sample.

10. A method for determining the presence of or predisposition to a disease associated with altered levels of expression of the polypeptide of claim 1 in a first mammalian subject, the method comprising: a) measuring the level of expression of the polypeptide in a sample from the first mammalian subject; and b) comparing the expression of said polypeptide in the sample of step (a) to the expression of the polypeptide present in a control sample from a second mammalian subject known not to have, or not to be predisposed to, said disease, wherein an alteration in the level of expression of the polypeptide in the first subject as compared to the control sample indicates the presence of or predisposition to said disease.

11. A method of identifying an agent that binds to the polypeptide of claim 1, the method comprising: (a) introducing said polypeptide to said agent; and (b) determining whether said agent binds to said polypeptide.

12. The method of claim 11 wherein the agent is a cellular receptor or a downstream effector.

13. A method for identifying a potential therapeutic agent for use in treatment of a pathology, wherein the pathology is related to aberrant expression or aberrant physiological interactions of the polypeptide of claim 1, the method comprising: (a) providing a cell expressing the polypeptide of claim 1 and having a property or function ascribable to the polypeptide; (b) contacting the cell with a composition comprising a candidate substance; and (c) determining whether the substance alters the property or function ascribable to the polypeptide; whereby, if an alteration observed in the presence of the substance is not observed when the cell is contacted with a composition in the absence of the substance, the substance is identified as a potential therapeutic agent.

14. A method for screening for a modulator of activity of or of latency or predisposition to a pathology associated with the polypeptide of claim 1, said method comprising: (a) administering a test compound to a test animal at increased risk for a pathology associated with the polypeptide of claim 1, wherein said test animal recombinantly expresses the polypeptide of claim 1;(b) measuring the activity of said polypeptide in said test animal after administering the compound of step (a); and (c) comparing the activity of said polypeptide in said test animal with the activity of said polypeptide in a control animal not administered said polypeptide, wherein a change in the activity of said polypeptide in said test animal relative to said control animal indicates the test compound is a modulator activity of or latency or predisposition to, a pathology associated with the polypeptide of claim 1.

15. The method of claim 14, wherein said test animal is a recombinant test animal that expresses a test protein transgene or expresses said transgene under the control of a promoter at an increased level relative to a wild-type test animal, and wherein said promoter is not the native gene promoter of said transgene.

16. A method for modulating the activity of the polypeptide of claim 1, the method comprising contacting a cell sample expressing the polypeptide of claim 1 with a compound that binds to said polypeptide in an amount sufficient to modulate the activity of the polypeptide.

17. A method of treating or preventing a pathology associated with the polypeptide of claim 1, the method comprising administering the polypeptide of claim 1 to a subject in which such treatment or prevention is desired in an amount sufficient to treat or prevent the pathology in the subject.

18. The method of claim 17, wherein the subject is a human.

19. A method of treating a pathological state in a mammal, the method comprising administering to the mammal a polypeptide in an amount that is sufficient to alleviate the pathological state, wherein the polypeptide is a polypeptide having an amino acid sequence at least 95% identical to a polypeptide comprising the amino acid sequence selected from the group consisting of SEQ ID NO:2n, wherein n is an integer between 1 and 77 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 77.

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 77.

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 77.

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 77.

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 77, 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 77.

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 77.

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.