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 82. The novel nucleic acids and polypeptides are referred to herein as NOV1a, NOV1b, NOV1c, NOV1d, NOV2a, NOV2b, NOV2c, NOV2d, NOV3a, NOV3b, etc. 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 82, 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 82. 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 82 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 82, 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 82. 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 82. 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 82 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 82 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 82 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 82 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 82, 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 82, 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 82, 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 82, 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 82, 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 82 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 82; 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 82 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 82; 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 82, 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 82 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 82, 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 82 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 82, 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 82.

[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 82, 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 82; 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 82 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 82; 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 82 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 82, 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 82, 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 82, 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 82. 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 82 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 82 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.

BRIEF DESCRIPTION OF THE DRAWINGS

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	CG108537-01	1	2	Prostein - Homo sapiens
NOV2a	CG51373-01	3	4	G-protein Coupled Receptor-like -
				Homo sapiens
NOV2b	13374639	5	6	G-protein Coupled Receptor-like -
				Homo sapiens
NOV2c	13374851	7	8	G-protein Coupled Receptor-like -
				Homo sapiens
NOV2d	13374640	9	10	G-protein Coupled Receptor-like -
				Homo sapiens
NOV2e	13374638	11	12	G-protein Coupled Receptor-like -
				Homo sapiens
NOV2f	13376161	13	14	G-protein Coupled Receptor-like -
				Homo sapiens
NOV2g	CG51373-08	15	16	G-protein Coupled Receptor-like -
				Homo sapiens
NOV2h	CG51373-09	17	18	G-protein Coupled Receptor-like -
				Homo sapiens
NOV3a	CG51514-01	19	20	BA438B23.1 (Neuronal leucine-rich
				repeat protein) Homo sapiens
NOV3b	13382215	21	22	BA438B23.1 (Neuronal leucine-rich
				repeat protein) (Homo sapiens
NOV3c	13375162	23	24	BA438B23.1 (Neuronal leucine-rich
				repeat protein) Homo sapiens
NOV3d	13374269	25	26	BA438B23.1 (Neuronal leucine-rich
				repeat protein) Homo sapiens
NOV3e	13375297	27	28	BA438B23.1 (Neuronal leucine-rich
				repeat protein) Homo sapiens
NOV3f	13375298	29	30	BA438B23.1 (Neuronal leucine-rich
				repeat protein) Homo sapiens
NOV3g	13375299	31	32	BA438B23.1 (Neuronal leucine-rich
				repeat protein) Homo sapiens
NOV3h	CG51514-02	33	34	BA438B23.1 (Neuronal leucine-rich
				repeat protein) Homo sapiens
NOV3i	CG51514-04	35	36	BA438B23.1 (Neuronal leucine-rich
				repeat protein) Homo sapiens
NOV4a	CG52053-01	37	38	SPINAL CORD-derived growth factor-
				B (MSTP036) (IRIS-expressed growth
				factor long form) (Platelet-derived
				growth factor D) - Homo sapiens
NOV4b	CG52053-03	39	40	SPINAL CORD-derived growth factor-
				B (MSTP036) (IRIS-expressed growth
				factor long form) (Platelet-derived
				growth factor D) - Homo sapiens
NOV4c	CG52053-04	41	42	SPINAL CORD-derived growth factor-
				B (MSTP036) (IRIS-expressed growth
				factor long form) (Platelet-derived
				growth factor D) - Homo sapiens
NOV4d	CG52053-05	43	44	SPINAL CORD-derived growth factor-
				B (MSTP036) (IRIS-expressed growth
				factor long form) (Platelet-derived
				growth factor D) - Homo sapiens
NOV4e	CG52053-06	45	46	SPINAL CORD-derived growth factor-
				B (MSTP036) (IRIS-expressed growth
				factor long form) (Platelet-derived
				growth factor D) - Homo sapiens
NOV4f	CG52053-07	47	48	SPINAL CORD-derived growth factor-
				B (MSTP036) (IRIS-expressed growth
				factor long form) (Platelet-derived
				growth factor D) - Homo sapiens
NOV4g	13376547	49	50	SPINAL CORD-derived growth factor-
				B (MSTP036) (IRIS-expressed growth
				factor long form) (Platelet-derived
				growth factor D) - Homo sapiens
NOV4h	13376546	51	52	SPINAL CORD-derived growth factor-
				B (MSTP036) (IRIS-expressed growth
				factor long form) (Platelet-derived
				growth factor D) - Homo sapiens
NOV4i	13376545	53	54	SPINAL CORD-derived growth factor-
				B (MSTP036) (IRIS-expressed growth
				factor long form) (Platelet-derived
				growth factor D) - Homo sapiens
NOV4j	13376544	55	56	SPINAL CORD-derived growth factor-
				B (MSTP036) (IRIS-expressed growth
				factor long form) (Platelet-derived
				growth factor D) - Homo sapiens
NOV4k	13376543	57	58	SPINAL CORD-derived growth factor-
				B (MSTP036) (IRIS-expressed growth
				factor long form) (Platelet-derived
				growth factor D) - Homo sapiens
NOV4l	13376542	59	60	SPINAL CORD-derived growth factor-
				B (MSTP036) (IRIS-expressed growth
				factor long form) (Platelet-derived
				growth factor D) - Homo sapiens
NOV4m	13376541	61	62	SPINAL CORD-derived growth factor-
				B (MSTP036) (IRIS-expressed growth
				factor long form) (Platelet-derived
				growth factor D) - Homo sapiens
NOV5a	CG52676-02	63	64	T cell immunoglobulin mucin-3 - Homo
				sapiens
NOV5b	191998702	65	66	T cell immunoglobulin mucin-3 - Homo
				sapiens
NOV5c	CG52676-01	67	68	T cell immunoglobulin mucin-3 - Homo
				sapiens
NOV5d	CG52676-03	69	70	T cell immunoglobulin mucin-3 - Homo
				sapiens
NOV5e	13382222	71	72	T cell immunoglobulin mucin-3 - Homo
				sapiens
NOV6a	CG52997-01	73	74	Human toll like receptor like molecule
				5 (TLR-L5) protein - Homo sapiens
NOV6b	CG52997-02	75	76	Human toll like receptor like molecule
				5 (TLR-L5) protein - Homo sapiens
NOV6c	CG52997-03	77	78	Human toll like receptor like molecule
				5 (TLR-L5) protein - Homo sapiens
NOV6d	CG52997-04	79	80	Human toll like receptor like molecule
				5 (TLR-L5) protein - Homo sapiens
NOV6e	CG52997-05	81	82	Human toll like receptor like molecule
				5 (TLR-L5) protein - Homo sapiens
NOV6f	13375304	83	84	Human toll like receptor like molecule
				5 (TLR-L5) protein - Homo sapiens
NOV6g	13376158	85	86	Human toll like receptor like molecule
				5 (TLR-L5) protein - Homo sapiens
NOV7a	CG55690-01	87	88	Frizzled 9 precursor (Frizzled-9) (Fz-9)
				(hFz9) (FzE6) - Homo sapiens
NOV7b	224699969	89	90	Frizzled 9 precursor (Frizzled-9) (Fz-9)
				(hFz9) (FzE6) - Homo sapiens
NOV7c	219938152	91	92	Frizzled 9 precursor (Frizzled-9) (Fz-9)
				(hFz9) (FzE6) - Homo sapiens
NOV7d	219938158	93	94	Frizzled 9 precursor (Frizzled-9) (Fz-9)
				(hFz9) (FzE6) - Homo sapiens
NOV7e	CG55690-02	95	96	Frizzled 9 precursor (Frizzled-9) (Fz-9)
				(hFz9) (FzE6) - Homo sapiens
NOV7f	CG55690-03	97	98	Frizzled 9 precursor (Frizzled-9) (Fz-9)
				(hFz9) (FzE6) - Homo sapiens
NOV7g	CG55690-04	99	100	Frizzled 9 precursor (Frizzled-9) (Fz-9)
				(hFz9) (FzE6) - Homo sapiens
NOV7h	CG55690-05	101	102	Frizzled 9 precursor (Frizzled-9) (Fz-9)
				(hFz9) (FzE6) - Homo sapiens
NOV7i	13376520	103	104	Frizzled 9 precursor (Frizzled-9) (Fz-9)
				(hFz9) (FzE6) - Homo sapiens
NOV7j	13376521	105	106	Frizzled 9 precursor (Frizzled-9) (Fz-9)
				(hFz9) (FzE6) - Homo sapiens
NOV8a	CG57049-01	107	108	Human phosphatidylethanolamine-
				binding protein - Homo sapiens
NOV8b	224699879	109	110	Human phosphatidylethanolamine-
				binding protein - Homo sapiens
NOV8c	175069519	111	112	Human phosphatidylethanolamine-
				binding protein - Homo sapiens
NOV8d	175069563	113	114	Human phosphatidylethanolamine-
				binding protein - Homo sapiens
NOV8e	CG57049-02	115	116	Human phosphatidylethanolamine-
				binding protein - Homo sapiens
NOV8f	13379525	117	118	Human phosphatidylethanolamine-
				binding protein - Homo sapiens
NOV8g	13379526	119	120	Human phosphatidylethanolamine-
				binding protein - Homo sapiens
NOV8h	13373853	121	122	Human phosphatidylethanolamine-
				binding protein - Homo sapiens
NOV8i	13373737	123	124	Human phosphatidylethanolamine-
				binding protein - Homo sapiens
NOV8j	13376382	125	126	Human phosphatidylethanolamine-
				binding protein - Homo sapiens
NOV8k	13373850	127	128	Human phosphatidylethanolamine-
				binding protein - Homo sapiens
NOV8l	13373849	129	130	Human phosphatidylethanolamine-
				binding protein - Homo sapiens
NOV9a	CG59538-01	131	132	B7 Related Protein - Homo sapiens
NOV9b	CG59538-02	133	134	B7 Related Protein - Homo sapiens
NOV9c	CG59538-03	135	136	B7 Related Protein - Homo sapiens
NOV9d	CG59538-04	137	138	B7 Related Protein - Homo sapiens
NOV9e	CG59538-05	139	140	B7 Related Protein - Homo sapiens
NOV9f	CG59538-06	141	142	B7 Related Protein - Homo sapiens
NOV9g	CG59538-07	143	144	B7 Related Protein - Homo sapiens
NOV9h	13382231	145	146	B7 Related Protein - Homo sapiens
NOV9i	13376726	147	148	B7 Related Protein - Homo sapiens
NOV9j	13382229	149	150	B7 Related Protein - Homo sapiens
NOV9k	13376724	151	152	B7 Related Protein - Homo sapiens
NOV9l	13376727	153	154	B7 Related Protein - Homo sapiens
NOV9m	13376728	155	156	B7 Related Protein - Homo sapiens
NOV10a	CG59932-01	157	158	Glioma pathogenesis-related protein
				(GliPR) (RTVP-1 protein) - Homo
				sapiens
NOV11a	CG94562-01	159	160	Novel human calcium-binding protein
				#14 - Homo sapiens
NOV11b	209886403	161	162	Novel human calcium-binding protein
				#14 - Homo sapiens
NOV11c	CG94562-02	163	164	Novel human calcium-binding protein
				#14 - Homo sapiens

[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 82; (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 82, 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 82; (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 82 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 82; (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 82 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 82; (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 82, 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 82 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 82; (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 82 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 82; 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 82 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 celutissue 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 82, 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 82, 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 82, 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 82, 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 82, is one that is sufficiently complementary to the nucleotide sequence of SEQ ID NO:2n−1, wherein n is an integer between 1 and 82, 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 82, 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, erg. 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 82, 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 82; or an anti-sense strand nucleotide sequence of SEQ ID NO:2n−1, wherein n is an integer between 1 and 82; or of a naturally occurring mutant of SEQ ID NO:2n−1, wherein n is an integer between 1 and 82.

[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 82, 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 Single Nucleotide Polymorphisms

[0072] 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.

[0073] 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.

[0074] 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.

[0075] 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).

[0076] 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.

[0077] NOVX Nucleic Acid and Polypeptide Variants

[0078] 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 82, 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 82. 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 82.

[0079] In addition to the human NOVX nucleotide sequences of SEQ ID NO:2n−1, wherein n is an integer between 1 and 82, 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.

[0080] 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 82, 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.

[0081] 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 82. 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.

[0082] 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.

[0083] 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.

[0084] 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×SCC, 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×SCC, 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 82, 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).

[0085] 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 82, 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×SCC, 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×SCC, 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.

[0086] 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 82, 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×SCC, 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×SCC, 25 mM Tris-HCI (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.

[0087] Conservative Mutations

[0088] 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 82, 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 82. 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.

[0089] 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 82, 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 82. 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 82; more preferably at least about 70% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 82; still more preferably at least about 80% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 82; even more preferably at least about 90% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 82; and most preferably at least about 95% homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 82.

[0090] 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 82, 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 82, such that one or more amino acid substitutions, additions or deletions are introduced into the encoded protein.

[0091] Mutations can be introduced any one of SEQ ID NO:2n−1, wherein n is an integer between 1 and 82, 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 82, the encoded protein can be expressed by any recombinant technology known in the art and the activity of the protein can be determined.

[0092] 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.

[0093] 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).

[0094] 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).

[0095] Interfering RNA

[0096] 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, WO 99/32619, 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.

[0097] 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.

[0098] 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.

[0099] 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.

[0100] 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′ WU 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.

[0101] 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.

[0102] 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.

[0103] 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.

[0104] 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.

[0105] 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.

[0106] 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.

[0107] 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.

[0108] 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.

[0109] 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 jig 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.

[0110] 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.

[0111] 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.

[0112] 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.

[0113] 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.

[0114] 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.

[0115] Production of RNAs

[0116] 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).

[0117] Lysate Preparation

[0118] 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.

[0119] 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% polyacrylarnide 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.

[0120] 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.

[0121] RNA Preparation

[0122] 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)).

[0123] 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.

[0124] Cell Culture

[0125] 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.

[0126] 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.

[0127] Antisense Nucleic Acids

[0128] 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 82, 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 82, 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 82, are additionally provided.

[0129] 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 (ie., also referred to as 5′ and 3′ untranslated regions).

[0130] 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).

[0131] 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).

[0132] 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 III or pol III promoter are preferred.

[0133] 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.

[0134] Ribozymes and PNA Moieties

[0135] 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.

[0136] 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 82). 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.

[0137] 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.

[0138] 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.

[0139] 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., 1 996.supra); or as probes or primers for DNA sequence and hybridization (See, Hyrup, et al., 1996, supra; Perry-O'Keefe, et al., 1996. supra).

[0140] 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.

[0141] 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.

[0142] NOVX Polypeptides

[0143] 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 82. 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 82, while still encoding a protein that maintains its NOVX activities and physiological functions, or a functional fragment thereof.

[0144] 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.

[0145] 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.

[0146] 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.

[0147] 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.

[0148] 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 82) 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.

[0149] 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.

[0150] In an embodiment, the NOVX protein has an amino acid sequence of SEQ ID NO:2n, wherein n is an integer between 1 and 82. In other embodiments, the NOVX protein is substantially homologous to SEQ ID NO:2n, wherein n is an integer between 1 and 82, and retains the functional activity of the protein of SEQ ID NO:2n, wherein n is an integer between 1 and 82, 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 82, and retains the functional activity of the NOVX proteins of SEQ ID NO:2n, wherein n is an integer between 1 and 82.

[0151] Determining Homology Between Two or More Sequences

[0152] 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”).

[0153] 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 82.

[0154] 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.

[0155] Chimeric and Fusion Proteins

[0156] 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 82, 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.

[0157] 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.

[0158] 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.

[0159] 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.

[0160] 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.

[0161] NOVX Agonists and Antagonists

[0162] 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.

[0163] 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.

[0164] Polypeptide Libraries

[0165] 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 SI nuc lease, 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.

[0166] 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.

[0167] Anti-NOVX Antibodies

[0168] Included in the invention are antibodies to NOVX proteins, or fragments of NOVX proteins. The term “antibody” as used herein refers to immunoglobulin molecules and immunologically active portions of immunoglobulin (Ig) molecules, i.e., molecules that contain an antigen binding site that specifically binds (immunoreacts with) an antigen. Such antibodies include, but are not limited to, polyclonal, monoclonal, chimeric, single chain, Fab, Fab and F(ab′)2 fragments, and an Fab expression library. In general, antibody molecules obtained from humans relates to any of the classes IgG, IgM, IgA, IgE and IgD, which differ from one another by the nature of the heavy chain present in the molecule. Certain classes have subclasses as well, such as IgG1, IgG2, and others. Furthermore, in humans, the light chain may be a kappa chain or a lambda chain. Reference herein to antibodies includes a reference to all such classes, subclasses and types of human antibody species.

[0169] 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 82, 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.

[0170] 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.

[0171] 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 including radioligand binding assays or similar assays known to skilled artisans.

[0172] 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.

[0173] 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.

[0174] Polyclonal Antibodies

[0175] 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).

[0176] 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).

[0177] Monoclonal Antibodies

[0178] 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.

[0179] 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.

[0180] 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.

[0181] 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).

[0182] 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.

[0183] 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.

[0184] 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.

[0185] 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.

[0186] Humanized Antibodies

[0187] 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)).

[0188] Human Antibodies

[0189] 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).

[0190] 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)).

[0191] 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.

[0192] 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.

[0193] 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.

[0194] 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.

[0195] 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.

[0196] Fab Fragments and Single Chain Antibodies

[0197] 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.

[0198] Bispecific Antibodies

[0199] 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.

[0200] Methods for making bispecific antibodies are known in the art. Traditionally, the recombinant production of bispecific antibodies is based on the co-expression of two immunoglobulin heavy-chain/light-chain pairs, where the two heavy chains have different specificities (Milstein and Cuello, Nature, 305:537-539 (1983)). Because of the random assortment of immunoglobulin heavy and light chains, these hybridomas (quadromas) produce a potential mixture of ten different antibody molecules, of which only one has the correct bispecific structure. The purification of the correct molecule is usually accomplished by affinity chromatography steps. Similar procedures are disclosed in WO 93/08829, published 13 May 1993, and in Traunecker et al., EMBO J., 10:3655-3659 (1991).

[0201] 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).

[0202] 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.

[0203] 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.

[0204] 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.

[0205] 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).

[0206] Antibodies with more than two valencies are contemplated. For example, trispecific antibodies can be prepared. Tutt et al., J. Immunol. 147:60 (1991).

[0207] 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).

[0208] Heteroconjugate Antibodies

[0209] 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.

[0210] Effector Function Engineering

[0211] 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).

[0212] Immunoconjugates

[0213] 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).

[0214] 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.

[0215] 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.

[0216] 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.

[0217] Immunoliposomes

[0218] 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.

[0219] 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).

[0220] Diagnostic Applications of Antibodies Directed Against the Proteins of the Invention

[0221] 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.

[0222] 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”).

[0223] 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 avidin/biotin; examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin, and examples of suitable radioactive material include 125I, 131I, 35S or 3H.

[0224] Antibody Therapeutics

[0225] 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.

[0226] 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.

[0227] 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.

[0228] Pharmaceutical Compositions of Antibodies

[0229] 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.

[0230] 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.

[0231] 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.

[0232] The formulations to be used for in vivo administration must be sterile. This is readily accomplished by filtration through sterile filtration membranes.

[0233] 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.

[0234] ELISA Assay

[0235] 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.

[0236] NOVX Recombinant Expression Vectors and Host Cells

[0237] 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.

[0238] 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).

[0239] 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.).

[0240] 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.

[0241] 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.

[0242] 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).

[0243] 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.

[0244] In another embodiment, the NOVX expression vector is a yeast expression vector. Examples of vectors for expression in yeast Saccharomyces cerivisae include pYepSec 1 (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.).

[0245] 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).

[0246] 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.

[0247] In another embodiment, the recombinant mammalian expression vector is capable of directing expression of the nucleic acid preferentially in a particular cell type (e.g., tissue-specific regulatory elements are used to express the nucleic acid). Tissue-specific regulatory elements are known in the art. Non-limiting examples of suitable tissue-specific promoters include the albumin promoter (liver-specific; Pinkert, et al., 1987. Genes Dev. 1: 268-277), lymphoid-specific promoters (Calame and Eaton, 1988. Adv. Immunol. 43: 235-275), in particular promoters of T cell receptors (Winoto and Baltimore, 1989. EMBO J 8: 729-733) and immunoglobulins (Baneiji, et al., 1983. Cell 33: 729-740; Queen and Baltimore, 1983. Cell 33: 741-748), neuron-specific promoters (e.g., the neurofilament promoter; Byme 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).

[0248] 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.

[0249] 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.

[0250] 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.

[0251] 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.

[0252] 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).

[0253] 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.

[0254] Transgenic NOVX Animals

[0255] 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.

[0256] 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 82, 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.

[0257] 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 82), 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 82, 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).

[0258] 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.

[0259] 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.

[0260] 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.

[0261] Clones of the non-human transgenic animals described herein can also be produced according to the methods described in Wilmut, et al., 1997. Nature 385: 810-813. In brief, a cell (e.g., a somatic cell) from the transgenic animal can be isolated and induced to exit the growth cycle and enter Go phase. The quiescent cell can then be fused, e.g., through the use of electrical pulses, to an enucleated oocyte from an animal of the same species from which the quiescent cell is isolated. The reconstructed oocyte is then cultured such that it develops to morula or blastocyte and then transferred to pseudopregnant female foster animal. The offspring borne of this female foster animal will be a clone of the animal from which the cell (e.g., the somatic cell) is isolated.

[0262] Pharmaceutical Compositions

[0263] 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.

[0264] 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.

[0265] 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.

[0266] 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.

[0267] 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.

[0268] 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.

[0269] 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.

[0270] 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.

[0271] 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.

[0272] 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.

[0273] 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.

[0274] The pharmaceutical compositions can be included in a container, pack, or dispenser together with instructions for administration.

[0275] Screening and Detection Methods

[0276] 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.

[0277] The invention further pertains to novel agents identified by the screening assays described herein and uses thereof for treatments as described, supra.

[0278] Screening Assays

[0279] 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.

[0280] 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.

[0281] 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.

[0282] 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.

[0283] 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.).

[0284] 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.

[0285] 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.

[0286] 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.

[0287] 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.

[0288] 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.

[0289] 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.

[0290] 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, Tritone® 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).

[0291] 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.

[0292] 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.

[0293] 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.

[0294] 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.

[0295] 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.

[0296] The invention further pertains to novel agents identified by the aforementioned screening assays and uses thereof for treatments as described herein.

[0297] Detection Assays

[0298] 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.

[0299] Chromosome Mapping

[0300] 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 82, 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.

[0301] 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.

[0302] 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.

[0303] 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.

[0304] 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).

[0305] 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.

[0306] 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.

[0307] 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.

[0308] Tissue Typing

[0309] 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).

[0310] 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.

[0311] 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).

[0312] 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 82, are used, a more appropriate number of primers for positive individual identification would be 500-2,000.

[0313] Predictive Medicine

[0314] 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.

[0315] 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.)

[0316] 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.

[0317] These and other agents are described in further detail in the following sections.

[0318] Diagnostic Assays

[0319] 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 82, 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.

[0320] 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.

[0321] 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.

[0322] 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.

[0323] 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.

[0324] Prognostic Assays

[0325] 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.

[0326] 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).

[0327] 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.

[0328] 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.

[0329] 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); Qp 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.

[0330] 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.

[0331] 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.

[0332] 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).

[0333] 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 SI 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.

[0334] 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.

[0335] 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.

[0336] 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.

[0337] 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.

[0338] 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.

[0339] 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.

[0340] 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.

[0341] Pharmacogenomics

[0342] 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.

[0343] 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.

[0344] 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.

[0345] 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.

[0346] 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.

[0347] Monitoring of Effects During Clinical Trials

[0348] 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.

[0349] 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.

[0350] 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.

[0351] Methods of Treatment

[0352] 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.

[0353] These methods of treatment will be discussed more fully, below.

[0354] Diseases and Disorders

[0355] 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.

[0356] 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.

[0357] 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).

[0358] Prophylactic Methods

[0359] 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.

[0360] Therapeutic Methods

[0361] 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 inbibits 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.

[0362] Stimulation of NOVX activity is desirable in situations in which NOVX is abnormally downregulated and/or in which increased NOVX activity is likely to have a beneficial effect. One example of such a situation is where a subject has a disorder characterized by aberrant cell proliferation and/or differentiation (e.g., cancer or immune associated disorders). Another example of such a situation is where the subject has a gestational disease (e.g., preclampsia).

[0363] Determination of the Biological Effect of the Therapeutic

[0364] 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.

[0365] 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.

[0366] Prophylactic and Therapeutic Uses of the Compositions of the Invention

[0367] 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.

[0368] 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.

[0369] 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.

[0370] The invention will be further described in the following examples, which do not limit the scope of the invention described in the claims.

EXAMPLES

Example A

Polynucleotide and Polypeptide Sequences, and Homology Data

Example 1

NOV1 CG108537, Sugar Transporter

[0371] The NOV1 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 1A.

TABLE 1A
NOV1 Sequence Analysis
NOV1a, CG108537-01	SEQ ID NO: 1	1702 bp
DNA Sequence	ORF Start: ATG at 21	ORF Stop: end of sequence
CCCTACCCGCCTGGCCCACTATGGTCCAGAGGCTGTGGGTGAGCCGCCTGCTGCGGCACCGGAAAGCC
CAGCTCTTGCTGGTCAACCTGCTAACCTTTGGCCTGGAGGTGTGTTTGGCCGCAGGCATCACCTATGT
GCCGCCTCTGCTGCTGGAAGTGGGGGTAGAGGAGAAGTTCATGACCATGGTGCTGGGTATTGGTCCAG
TGCTGGGCCTGGTCTGTGTCCCGCTCCTAGGCTCAGCCAGTGACCACTGGCGTGGACGCTATGGCCGC
CGCCGGCCCTTCATCTGGGCACTGTCCTTGGGCATCCTGCTGAGCCTCTTTCTCATCCCAAGGGCCGG
CTGGCTAGCAGGGCTGCTGTGCCCGGATCCCAGGCCCCTGGAGCTGGCACTGCTCATCCTGGGCGTGG
GGCTGCTGGACTTCTGTGGCCAGGTGTGCTTCACTCCACTGGAGGCCCTGCTCTCTGACCTCTTCCGG
GACCCGGACCACTGTCGCCAGGCCTACTCTGTCTATGCCTTCATGATCAGTCTTGGGGGCTGCCTGGG
CTACCTCCTGCCTGCCATTGACTGGGACACCAGTGCCCTGGCCCCCTACCTGGGCACCCAGGAGGAGT
GCCTCTTTGGCCTGCTCACCCTCATCTTCCTCACCTGCGTAGCAGCCACACTGCTGGTGGCTGAGGAG
GCAGCGCTGGGCCCCACCGAGCCAGCAGAAGGGCTGTCGGCCCCCTCCTTGTCGCCCCACTGCTGTCC
ATGCCGGGCCCGCTTGGCTTTCCGGAACCTGGGCGCCCTGCTTCCCCGGCTGCACCAGCTGTGCTGCC
GCATGCCCCGCACCCTGCGCCGGCTCTTCGTGGCTGAGCTGTGCAGCTGGATGGCACTCATGACCTTC
ACGCTGTTTTACACGGATTTCGTGGGCGAGGGGCTGTACCAGGGCGTGCCCAGAGCTGAGCCGGGCAC
CGAGGCCCGGAGACACTATGATGAAGGTGTTCGGATGGGCAGCCTGGGGCTGTTCCTGCAGTGCGCCA
TCTCCCTGGTCTTCTCTCTGGTCATGGACCGGCTGGTGCAGCGATTCGGCACTCGAGCAGTCTATTTG
GCCAGTGTGGCAGCTTTCCCTGTGGCTGCCGGTGCCACATGCCTGTCCCACAGTGTGGCCGTGGTGAC
AGCTTCAGCCGCCCTCACCGGGTTCACCTTCTCAGCCCTGCAGATCCTGCCCTACACACTGGCCTCCC
TCTACCACCGGGAGAAGCAGGTGTTCCTGCCCAAATACCGAGGGGACACTGGAGGTGCTAGCAGTGAG
GACAGCCTGATGACCAGCTTCCTGCCAGGCCCTAAGCCTGGAGCTCCCTTCCCTAATGGACACGTGGG
TGCTGGAGGCAGTGGCCTGCTCCCACCTCCACCCGCGCTCTGCGGGGCCTCTGCCTGTGATGTCTCCG
TACGTGTGGTGGTGGGTGAGCCCACCGAGGCCAGGGTGGTTCCGGGCCGGGGCATCTGCCTGGACCTC
GCCATCCTGGATAGTGCCTTCCTGCTGTCCCAGGTGGCCCCATCCCTGTTTATGGGCTCCATTGTCCA
GCTCAGCCAGTCTGTCACTGCCTATATGGTGTCTGCCGCAGGCCTGGGTCTGGTCGCCATTTACTTTG
CTACACAGGTAGTATTTGACAAGAGCGACTTGGCCAAATACTCAGCGTAGAAAACTTCCAGCACATTG
GG
NOV1a, CG108537-01
Protein Sequence	SEQ ID NO: 2	553 aa	MW at 59321.9kD
MVQRLWVSRLLRHRKAQLLLVNLLTFGLEVCLAAGITYVPPLLLEVGVEEKFMTMVLGIGPVLGLVCV
PLLGSASDHWRGRYGRRRPFIWALSLGILLSLFLIPRAGWLAGLLCPDPRPLELALLILGVGLLDFCG
QVCFTPLEALLSDLFRDPDHCRQAYSVYAFMISLGGCLGYLLPAIDWDTSALAPYLGTQEECLFGLLT
LIFLTCVAATLLVAEEAALGPTEPAEGLSAPSLSPHCCPCRARLAFRNLGALLPRLHQLCCRMPRTLR
RLFVAELCSWMALMTFTLFYTDFVGEGLYQGVPRAEPGTEARRHYDEGVRMGSLGLFLQCAISLVFSL
VMDRLVQRFGTRAVYLASVAAFPVAAGATCLSHSVAVVTASAALTGFTFSALQILPYTLASLYHREKQ
VFLPKYRGDTGGASSEDSLMTSFLPGPKPGAPFPNGHVGAGGSGLLPPPPALCGASACDVSVRVVVGE
PTEARVVPGRGICLDLAILDSAFLLSQVAPSLFMGSIVQLSQSVTAYMVSAAGLGLVAIYFATQVVFD
KSDLAKYSA

[0372] Further analysis of the NOV1 a protein yielded the following properties shown in Table 1B.

TABLE 1B
Protein Sequence Properties NOV1a
SignalP	Cleavage site between residues 34 and 35
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 −17.44
	PSG score: −21.84
	GvH: von Heijne's method for signal seq. recognition
	GvH score (threshold: −2.1): −3.14
	possible cleavage site: between 35 and 36
	>>> 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: 12
	INTEGRAL	Likelihood =	−4.73	Transmembrane	18-34
	INTEGRAL	Likelihood =	−7.11	Transmembrane	55-71
	INTEGRAL	Likelihood =	−6.53	Transmembrane	87-103
	INTEGRAL	Likelihood =	−4.09	Transmembrane	122-138
	INTEGRAL	Likelihood =	−1.70	Transmembrane	165-181
	INTEGRAL	Likelihood =	−9.24	Transmembrane	202-218
	INTEGRAL	Likelihood =	−0.75	Transmembrane	274-290
	INTEGRAL	Likelihood =	−6.00	Transmembrane	326-342
	INTEGRAL	Likelihood =	−0.48	Transmembrane	356-372
	INTEGRAL	Likelihood =	−0.00	Transmembrane	375-391
	INTEGRAL	Likelihood =	−1.12	Transmembrane	488-504
	INTEGRAL	Likelihood =	−2.28	Transmembrane	527-543
	PERIPHERAL	Likelihood =	1.11 (at 459)
	ALOM score: −9.24 (number of TMSs: 12)
	MTOP: Prediction of membrane topology (Hartmann et al.)
	Center position for calculation: 25
	Charge difference: −7.5 C(−1.0)-N(6.5)
	N >= C: N-terminal side will be inside
	>>> membrane topology: type 3a
	MITDISC: discrimination of mitochondrial targeting seq
	R content:	4	Hyd Moment (75):	11.22
	Hyd Moment (95):	8.66	G content:	1
	D/E content:	1	S/T content:	2
	Score: −0.21
	Gavel: prediction of cleavage sites for mitochondrial preseq
	R-2 motif at 24 HRK|AQ
	NUCDISC: discrimination of nuclear localization signals
	pat4: RHRK (3) at 12
	pat4: RRRP (4) at 84
	pat7: none
	bipartite: none
	content of basic residues: 7.2%
	NLS Score: −0.03
	KDEL: ER retention motif in the C-terminus: none
	ER Membrane Retention Signals:
	XXRR-like motif in the N-terminus: VQRL
	KKXX-like motif in the C-terminus: AKYS
	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):
	66.7%: endoplasmic reticulum
	22.2%: vesicles of secretory system
	11.1%: nuclear
	>> prediction for CG108537-01 is end (k = 9)

Example 2. NOV 2, CG51373: Nephrin like.

[0373] The NOV2 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 2A.

TABLE 2A
NOV2 Sequence Analysis
NOV2a, CG51373-01	SEQ ID NO: 3	1230 bp
DNA Sequence	ORF Start: ATG at 1	ORF Stop: end of sequence
ATGCATTTGACTCTGGAAGTCTTAAACCATGGCCCCTTCCCTCTAAACCTTTCCTCCATTGCTTACAA
TCATGGAACTGTGTTTGGCCACTGGAAGAATAACGTCACTCGGGAAACGCTGGTGAAAGTAAAAGATG
CTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGGAAGGAAACATTT
CTGGTGAATGAGGAGGCAACGGGCGAGACCTCAGGAGACAATGTTGTTCATTCTAGGAATCTGTCTCA
GACAATCTTCATCACCCGGAAACGATGGGAGGGGACCCAGACCCGCTTCAGCCAGGAGCCAGCTGACC
AGACGGTGGTGGCTGGACAGCGGGCCGTGCTCCCCTGTGTGCTGCTCAACTACTCTGGAATTGTGCAA
TGGACCAAGGACGGGCTGGCCCTGGGCATGGGCCAGGCCCTCAAAGCCTGGCCACGGTACCGGGTTGT
GGGCTCCGCAGACGCTGGGCAGTACAACCTGGAGATCACAGATGCTGAGCTCTCTGACGACGCCTCTT
ACGAGTGCCAGGCCACGGAGGCCGCCCTGCGCTCTCGGCGGGCCAAACTCACCGTGCTCATCCCCCCA
GAGGACACCAGGATTGACGGAGGCCCTGTGATTCTACTGCAGGCAGGCACCCCCCACAACCTCACATG
CCGGGCCTTCAATGCGAAGCCTGCTGCCACCATCATCTGGTTCCGGGACGGGACGCAGCAGGAGGGCG
CTGTGGCCAGCACGGAATTGCTGAAGGATGGGAAGAGGGAGACCACCGTGAGCCAACTGCTTATTAAC
CCCACGGACCTGGACATAGGGCGTGTCTTCACTTGCCGAAGCATGAACGAAGCCATCCCTAGTGGCAA
GGAGACTTCCATCGAGCTGGATGTGCACCGTGAGTGGGCTGGGGGGAGCAGTCTGGAGCAGGGGGGTG
GAAGAAGGGGTGTGTTTGAGAAGCACACTCTTAGTTTGAGAAACACAAACTAAGAGTCCCCCTATGGT
CCCCAGGACAAACGCTTGCCTTCTTCACATCTTTCATTCCCTGGATTGAACCATGGGGACTAAGGGCT
GGTAGAGCATTGGCTGTGGAGTCAGGCAGTCCCCAGGTCTAAACCAGCCTGTTATTAGTCAATGGTTT
ACACTCTCTGGGCCTCGGTTTCCAGTTCTGTATACTGTATATTGCAAAAGATAAAATACTGGCCTACA
GCCCCA
NOV2a, CG51373-01
Protein Sequence	SEQ ID NO: 4	334 aa	MW at 36655.8kD
MHLTLEVLNHGPFPLNLSSIAYNHGTVFGHWKNNVTRETLVKVKDAEDQLGARVGYIELDLNSGKETF
LVNEEATGETSGDNVVHSRNLSQTIFITRKRWEGTQTRFSQEPADQTVVAGQRAVLPCVLLNYSGIVQ
WTKDGLALGMGQALKAWPRYRVVGSADAGQYNLEITDAELSDDASYECQATEAALRSRRAKLTVLIPP
EDTRIDGGPVILLQAGTPHNLTCRAFNAKPAATIIWFRDGTQQEGAVASTELLKDGKRETTVSQLLIN
PTDLDIGRVFTCRSMNEAIPSGKETSIELDVHREWAGGSSLEQGGGRRGVFEKHTLSLRNTN

[0374] SNP 13374639 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 2B

TABLE 2B
NOV2b Sequence Analysis
NOV2b, 13374639	SEQ ID NO: 5	1230 bp
DNA Sequence	ORF Start: ATG at 1	ORF Stop: end of sequence
ATGCATTTGACTCTGGAAGTCTTAAACCATGGCCCCTTCCCTCTAAACCTTTCCTCCATTGCTTACAA
TCATGGAACTGTGTTTGGCCACTGGAAGAATAACGTCACTCGGGAAACGCTGGTGAAAGTAAAAGATG
CTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGGAAGGAAACATTT
CTGGTGAATGAGGAGGCAACGGGCGAGACCTCAGGAGACAATGTTGTTCATTCTAGGAATCTGTCTCA
GACAATCTTCATCACCCGCAAACGATGGGAGGGGACCCAGACCCGCTTCAGCCAGGAGCCAGCTGACC
AGACGGTGGTGGCTGGACAGCGGGCCGTGCTCCCCTGTGTGCTGCTCAACTACTCTGGAATTGTGCAA
TGGACCAAGGACGGGCTGGTCCTGGGCATGGGCCAGGCCCTCAAAGCCTGGCCACGGTACCGGGTTGT
GGGCTCCGCAGACGCTGGGCAGTACAACCTGGAGATCACAGATGCTGAGCTCTCTGACGACGCCTCTT
ACGAGTGCCAGGCCACGGAGGCCGCCCTGCGCTCTCGGCGGGCCAAACTCACCGTGCTCATCCCCCCA
GAGGACACCAGGATTGACGGAGGCCCTGTGATTCTACTGCAGGCAGGCACCCCCCACAACCTCACATG
CCGGGCCTTCAATGCGAAGCCTGCTGCCACCATCATCTGGTTCCGGGACGGGACGCAGCAGGAGGGCG
CTGTGGCCAGCACGGAATTGCTGAAGGATGGGAAGAGGGAGACCACCGTGAGCCAACTGCTTATTAAC
CCCACGGACCTGGACATAGGGCGTGTCTTCACTTGCCGAAGCATGAACGAAGCCATCCCTAGTGGCAA
GGAGACTTCCATCGAGCTGGATGTGCACCGTGAGTGGGCTGGGGGGAGCAGTCTGGAGCAGGCGGGTG
GAAGAAGGGGTGTGTTTGAGAAGCACACTCTTAGTTTGAGAAACACAAACTAAGAGTCCCCCTATGGT
CCCCAGGACAAACGCTTGCCTTCTTCACATCTTTCATTCCCTGGATTGAACCATGGGGACTAAGGGCT
GGTAGAGCATTGGCTGTGGAGTCAGGCAGTCCCCAGGTCTAAACCAGCCTGTTATTAGTCAATGGTTT
ACACTCTCTGGGCCTCGGTTTCCAGTTCTGTATACTGTATATTGCAAAAGATAAAATACTGGCCTACA
GCCCCA
NOV2b, 13374639
Protein Sequence	SEQ ID NO: 6	334 aa	MW at 36655.8kD
MHLTLEVLNHGPFPLNLSSIAYNHGTVFGHWKNNVTRETLVKVKDAEDQLGARVGYIELDLNSGKETF
LVNEEATGETSGDNVVHSRNLSQTIFITRKRWEGTQTRFSQEPADQTVVAGQRAVLPCVLLNYSGIVQ
WTKDGLVLGMGQALKAWPRYRVVGSADAGQYNLEITDAELSDDASYECQATEAALRSRRAKLTVLIPP
EDTRIDGGPVILLQAGTPHNLTCRAFNAKPAATIIWFRDGTQQEGAVASTELLKDGKRETTVSQLLIN
PTDLDIGRVFTCRSMNEAIPSGKETSIELDVHREWAGGSSLEQGGGRRGVFEKHTLSLRNTN

[0375] SNP 13374851 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 2C

TABLE 2C
NOV2c Sequence Analysis
NOV2c, 13374851	SEQ ID NO: 7	1230 bp
DNA Sequence	ORF Start: ATG at 1	ORF Stop: end of sequence
ATGCATTTGACTCTGGAAGTCTTAAACCATGGCCCCTTCCCTCTAAACCTTTCCTCCATTGCTTACAA	+TL,43
TCATGGAACTGTGTTTGGCCACTGGAAGAATAACGTCACTCGGGAAACGCTGGTGAAAGTAAAAGATG
CTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGGAAGGAAACATTT
CTGGTGAATGAGGAGGCAACGGGCGAGACCTCAGGAGACAATGTTGTTCATTCTAGGAATCTGTCTCA
GACAATCTTCATCACCCGGAAACGATGGGAGGGGACCCAGACCCGCTTCAGCCAGGACCCAGCTGACC
AGACGGTGGTGGCTGGACAGCGGGCCGTGCTCCCCTGTGTGCTGCTCAACTACTCTGGAATTGTGCAA
TGGACCAAGGACGGGCTGGCCCTGGGCATGGGCCAGGCCCTCAAAGCCTGGCCACGGTACCGGGTTGT
GGGCTCCACAGACGCTGGGCAGTACAACCTGGAGATCACAGATGCTGAGCTCTCTGACGACGCCTCTT
ACGAGTGCCAGGCCACGGAGGCCGCCCTGCGCTCTCGGCGGGCCAAACTCACCGTGCTCATCCCCCCA
GAGGACACCAGGATTGACGGAGGCCCTGTGATTCTACTGCAGGCAGGCACCCCCCACAACCTCACATG
CCGGGCCTTCAATGCGAAGCCTGCTGCCACCATCATCTGGTTCCGGGACGGGACGCAGCAGGAGGGCG
CTGTGGCCAGCACGGATTGCTGAAGGATGGGAAGAGGGAGACCACCGTGAGCCAACTGCTTATTAAC
CCCACGGACCTGGACATAGGGCGTGTCTTCACTTGCCGAAGCATGAACGAAGCCATCCCTAGTGGCAA
GGAGACTTCCATCGAGCTGGATGTGCACCGTGAGTGGGCTGGGGGGAGCAGTCTGGAGCAGGGGGGTG
GAAGAAGGGGTGTGTTTGAGAAGCACACTCTTAGTTTGAGAAACACAAACTAAGAGTCCCCCTATGGT
CCCCAGGACAAACGCTTGCCTTCTTCACATCTTTCATTCCCTGGATTGAACCATGGGGACTAAGGGCT
GGTAGAGCATTGGCTGTGGAGTCAGGCAGTCCCCAGGTCTAAACCAGCCTGTTATTAGTCAATGGTTT
ACACTCTCTGGGCCTCGGTTTCCAGTTCTGTATACTGTATATTGCAAAAGATAAAATACTGGCCTACA
GCCCCA
NOV2c, 13374851
Protein Sequence	SEQ ID NO: 8	334 aa	MW at 36655.8kD
MHLTLEVLNHGPFPLNLSSIAYNHGTVFGHWKNNVTRETLVKVKDAEDQLGARVGYIELDLNSGKETF
LVNEEATGETSGDNVVHSRNLSQTIFITRKRWEGTQTRFSQEPADQTVVAGQRAVLPCVLLNYSGIVQ
WTKDGLALGMGQALKAWPRYRVVGSTDAGQYNLEITDAELSDDASYECQATEAALRSRRAKLTVLIPP
EDTRIDGGPVILLQAGTPHNLTCRAFNAKPAATIIWFRDGTQQEGAVASTELLKDGKRETTVSQLLIN
PTDLDIGRVFTCRSMNEAIPSGKETSIELDVHREWAGGSSLEQGGGRRGVFEKHTLSLRNTN

[0376] SNP 13374640 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 2D

TABLE 2D
NOV2d Sequence Analysis
NOV2d, 13374640	SEQ ID NO: 9	1230 bp
DNA Sequence	ORF Start: ATG at 1	ORF Stop: end of sequence
ATGCATTTGACTCTGGAAGTCTTAAACCATGGCCCCTTCCCTCTAAACCTTTCCTCCATTGCTTACAA
TCATGGAACTGTGTTTGGCCACTGGAAGAATAACGTCACTCGGGAAACGCTGGTGAAAGTAAAAGATG
CTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGGAAGGAAACATTT
CTGGTGAATGAGGAGGCAACGGGCGAGACCTCAGGAGACAATGTTGTTCATTCTAGGAATCTGTCTCA
GACAATCTTCATCACCCGGAAACGATGGGAGGGGACCCAGACCCGCTTCAGCCAGGAGCCAGCTGACC
AGACGGTGGTGGCTGGACAGCGGGCCGTGCTCCCCTGTGTGCTGCTCAACTACTCTGGAATTGTGCAA
TGGACCAAGGACGGGCTGGCCCTGGGCATGGGCCAGGCCCTCAAAGCCTGGCCACGGTACCGGGTTGT
GGGCTCCGCAGACGCTGGGCAGTACAACCTGGAGATCACAGATGCTGAGCTCTCTGACGACGCCTCTT
ACGAGTGCCAGGTCACGGAGGCCGCCCTGCGCTCTCGGCGGGCCAAACTCACCGTGCTCATCCCCCCA
GAGGACACCAGGATTGACGGAGGCCCTGTGATTCTACTGCAGGCAGGCACCCCCCACAACCTCACATG
CCGGGCCTTCAATGCGAAGCCTGCTGCCACCATCATCTGGTTCCGGGACGGGACGCAGCAGGAGGGCG
CTGTGGCCAGCACGGAATTGCTGAAGGATGGGAAGAGGGAGACCACCGTGAGCCAACTGCTTATTAAC
CCCACGGACCTGGACATAGGGCGTGTCTTCACTTGCCGAAGCATGAACGAAGCCATCCCTAGTGGCAA
GGAGACTTCCATCGAGCTGGATGTGCACCGTGAGTGGGCTGGGGGGAGCAGTCTGGAGCAGGGGGGTG
GAAGAAGGGGTGTGTTTGAGAAGCACACTCTTAGTTTGAGAAACACAAACTAAGAGTCCCCCTATGGT
CCCCAGGACAAACGCTTGCCTTCTTCACATCTTTCATTCCCTGGATTGAACCATGGGGACTAAGGGCT
GGTAGAGCATTGGCTGTGGAGTCAGGCAGTCCCCAGGTCTAAACCAGCCTGTTATTAGTCAATGGTTT
ACACTCTCTGGCCCTCGGTTTCCAGTTCTGTATACTGTATATTGCAAAAGATAAAATACTGGCCTACA
GCCCCA
NOV2d, 13374640				+TL,43
Protein Sequence	SEQ ID NO: 10	334 aa	MW at 36655.8kD
MHLTLEVLNHGPFPLNLSSIAYNHGTVFGHWKNNVTRETLVKVKDAEDQLGARVGYIELDLNSGKETF
LVNEEATGETSGDNVVHSRNLSQTIFITRKRWEGTQTRFSQEPADQTVVAGQRAVLPCVLLNYSGIVQ
WTKDGLALGMGQALKAWPRYRVVGSADAGQYNLEITDAELSDDASYECQVTEAALRSRRAKLTVLIPP
EDTRIDGGPVILLQAGTPHNLTCRAFNAKPAATIIWFRDGTQQEGAVASTELLKDGKRETTVSQLLIN
PTDLDIGRVFTCRSMNEAIPSGKETSIELDVHREWAGGSSLEQGGGRRGVFEKHTLSLRNTN

[0377] SNP 13374638 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 2E

TABLE 2E
NOV2e Sequence Analysis
NOV2e, 13374638	SEQ ID NO: 11	1230 bp
DNA Sequence	ORF Start: ATG at 1	ORF Stop: end of sequence
ATGCATTTGACTCTGGAAGTCTTAAACCATGGCCCCTTCCCTCTAAACCTTTCCTCCATTGCTTACAA
TCATGGAACTGTGTTTGGCCACTGGAAGAATAACGTCACTCGGGAAACGCTGGTGAAAGTAAAAGATG
CTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGGAAGGAAACATTT
CTGGTGAATGAGGAGGCAACGGGCGAGACCTCAGGAGACAATGTTGTTCATTCTAGGAATCTGTCTCA
GACAATCTTCATCACCCGGAAACGATGGGAGGGGACCCAGACCCGCTTCAGCCAGGAGCCAGCTGACC
AGACGGTGGTGGCTGGACAGCGGGCCGTGCTCCCCTGTGTGCTGCTCAACTACTCTGGAATTGTGCAA
TGGACCAAGGACGGGCTGGCCCTGGCCATGGGCCAGGCCCTCAAAGCCTGGCCACGGTACCGGGTTGT
GGGCTCCGCAGACGCTGGGCAGTACAACCTGGAGATCACAGATGCTGAGCTCTCTGACGACGCCTCTT
ACGAGTGCCAGGCCACGGAGGCCGCCCTGCGCTCTCGGCGGGCCAAACTCACCGTGCTCATCCCCCCA
GAGGACACCAGGATTGACGGAGGCCCTGTGATTCTACTGCAGGCAGGCACCCCCCACAACCTCACATG
CCGGGCCTTCAATGCGAAGCCTGCTGCCACCATCATCTGGTTCCGGGACGGGACGCAGCGGGAGGGCG
CTGTGGCCAGCACGGAATTGCTGAAGGATGGGAAGAGGGAGACCACCGTGAGCCAACTGCTTATTAAC
CCCACGGACCTGGACATAGGGCGTGTCTTCACTTGCCGAAGCATGAACGAAGCCATCCCTAGTGGCAA
GGAGACTTCCATCGAGCTGGATGTGCACCGTGAGTGGGCTGGGGGGAGCAGTCTGGAGCAGGGGGGTG
GAAGAAGGGGTGTGTTTGAGAAGCACACTCTTAGTTTGAGAAACACAAACTAAGAGTCCCCCTATGGT
CCCCAGGACAAACGCTTGCCTTCTTCACATCTTTCATTCCCTGGATTGAACCATGGGGACTAAGGGCT
GGTAGAGCATTGGCTGTGGAGTCAGGCAGTCCCCAGGTCTAAACCAGCCTGTTATTAGTCAATGGTTT
ACACTCTCTGGGCCTCGGTTTCCAGTTCTGTATACTGTATATTGCAAAAGATAAAATACTGGCCTACA
GCCCCA
NOV2e, 13374638
Protein Seqence	SEQ ID NO: 12	334 aa	MW at 36655.8kD
MHLTLEVLNHGPFPLNLSSIAYNHGTVFGHWKNNVTRETLVKVKDAEDQLGARVGYIELDLNSGKETF
LVNEEATGETSGDNVVHSRNLSQTIFITRKRWEGTQTRFSQEPADQTVVAGQRAVLPCVLLNYSGIVQ
WTKDGLALGMGQALKAWPRYRVVGSADAGQYNLEITDAELSDDASYECQATEAALRSRRAKLTVLIPP
EDTRIDGGPVILLQAGTPHNLTCRAFNAKPAATIIWFRDGTQREGAVASTELLKDGKRETTVSQLLIN
PTDLDIGRVFTCRSMNEAIPSGKETSIELDVHREWAGGSSLEQGGGRRGVFEKHTLSLRNTN

[0378] SNP 13376161 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 2F

TABLE 2F
NOV2f Sequence Analysis
NOV2f, 13376161	SEQ ID NO: 13	1230 bp
DNA Sequence	ORF Start: ATG at 1	ORF Stop: end of sequence
ATGCATTTGACTCTGGAAGTCTTAAACCATGGCCCCTTCCCTCTAAACCTTTCCTCCATTGCTTACAA
TCATGGAACTGTGTTTGGCCACTGGAAGAATAACGTCACTCGGGAAACGCTGGTGAAAGTAAAAGATG
CTGAAGATCAGTTGGGTGCACGAGTGGGTTACATCGAACTGGATCTCAACAGCGGGAAGGAAACATTT
CTGGTGAATGAGGAGGCAACGGGCGAGACCTCAGGAGACAATGTTGTTCATTCTAGGAATCTGTCTCA
GACAATCTTCATCACCCGGAAACGATGGGAGGGGACCCAGACCCGCTTCAGCCAGGAGCCAGCTGACC
AGACCGTGGTGGCTGGACAGCGGGCCGTGCTCCCCTGTGTGCTGCTCAACTACTCTGGAATTGTGCAA
TGGACCAAGGACGGGCTGGCCCTGGGCATGGGCCAGGCCCTCAAAGCCTGGCCACGGTACCGGGTTGT
GGGCTCCGCAGACGCTGGGCAGTACAACCTGGAGATCACAGATGCTGAGCTCTCTGACGACGCCTCTT
ACGAGTGCCAGGCCACGGAGGCCGCCCTGCGCTCTCGGCGGGCCAAACTCACCGTGCTCATCCCCCCA
GAGGACACCAGGATTGACGGAGGCCCTGTGATTCTACTGCAGGCAGGCACCCCCCACAACCTCACATG
CCGGGCCTTCAATGCGAAGCCTGCTGCCACCATCATCTGGTTCCGGGACGGGACGCAGCAGGAGGCCG
CTGTGGCCAGCACGGAATTGCTGAAGGATGGGAAGAGGGAGACCACCGTGAGCCAACTGCTTATTAAC
CCCACGGACCTGGACATAGGGCGTGTCTTCACTTGCCGAAGCATGAACGAAGCCATCCCTAGTGGCAA
GGAGACTTCCGTCGAGCTGGATGTGCACCGTGAGTGGGCTGGGGGGAGCAGTCTGGAGCAGGGGGGTG
GAAGAAGGGGTGTGTTTGAGAAGCACACTCTTAGTTTGAGAAACACAAACTAAGAGTCCCCCTATGGT
CCCCAGGACAAACGCTTGCCTTCTTCACATCTTTCATTCCCTGGATTGAACCATGGGGACTAAGGGCT
GGTAGAGCATTGGCTGTGGAGTCAGGCAGTCCCCAGGTCTAAACCAGCCTGTTATTAGTCAATGGTTT
ACACTCTCTGGGCCTCGGTTTCCAGTTCTGTATACTGTATATTGCAAAAGATAAAATACTGGCCTACA
GCCCCA
NOV2f, 13376161
Protein Sequence	SEQ ID NO: 14	334 aa	MW at 36655.8kD
MHLTLEVLNHGPFPLNLSSIAYHGTVFGHWKNNVTRETLVKVKDAEDQLGARVGYIELDLNSGKETF
LVNEEATGETSGDNVVHSRNLSQTIFITRKRWEGTQTRFSQEPADQTVVAGQRAVLPCVLLNYSGIVQ
WTKDGLALGMGQALKAWPRYRVVGSADAGQYNLEITDAELSDDASYECQATEAALRSRRAKLTVLIPP
EDTRIDGGPVILLQAGTPHNLTCRAFNAKPAATIIWFRDGTQQEGAVASTELLKDGKRETTVSQLLIN
PTDLDIGRVFTCRSMNEAIPSGKETSVELDVHREWAGGSSLEQGGGRRGVFEKHTLSLRNTN

[0379] CG51373-08 and CG51373-09 clones were analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 2G

TABLE 2G:
NOV2g, CG51373-08	SEQ ID NO: 15	2128 bp
DNA Sequence	ORF Start: ATG at 31	ORF Stop: end of sequence
CAATGGACCAAGGACGGGCTGGCCCTGGGCATGGGCCAGGGCCTCAAAGCCTGGCCACGGTACCGGGT
TGTGGGCTCCGCAGACGCTGGGCAGTACAACCTGGAGATCACAGATGCTGAGCTCTCTGACGACGCCT
CTTACGAGTGCCAGGCCACGGAGGCCGCCCTGCGCTCTCGGCGGGCCAAACTCACCGTGCTCATCCCC
CCAGAGGACACCAGGATTGACGGAGGCCCTGTGATTCTACTGCAGGCAGGCACCCCCCACAACCTCAC
ATGCCGGGCCTTCAATGCGAAGCCTGCTGCCACCATCATCTGGTTCCGGGACGGGACGCAGCAGGAGG
GCGCTGTGGCCAGCACGGAATTGCTGAAGGATGGGAAGAGGGAGACCACCGTGAGCCAACTGCTTATT
AACCCCACGGACCTGGACATAGGGCGTGTCTTCACTTGCCGAAGCATGAACGAAGCCATCCCTAGTGG
CAAGGAGACTTCCATCGAGCTGGATGTGCACCACCCTCCTACAGTGACCCTGTCCATTGAGCCACAGA
CGGTGCAGGAGGGTGAGCGTGTTGTCTTTACCTGCCAGGCCACAGCCAACCCCGAGATCTTGGACTAC
AGGTGGGCCAAAGGGGGTTTCTTGATTGAAGACGCCCACGAGAGTCGCTATGAGACAAATGTGGATTA
TTCCTTTTTCACGGAGCCTGTGTCTTGTGAGGTTCACAACAAAGTGGGAAGCACCAATGTCAGCACTT
TAGTAAATGTCCACTTTGCTCCCCGGATTGTAGTTGACCCCAAACCCACAACCACAGACATTGGCTCT
GATGTGACCCTTACCTGTGTCTGGGTTGGGAATCCCCCCCTCACTCTCACCTGGACCAAAAAGCACTC
AAATATGGTCCTGAGTAACAGCAACCAGCTGCTGCTGAAGTCGGTGACTCAGGCAGACGCTGGCACCT
ACACCTGCCGGGCCATCGTGCCTCGAATCGGAGTGGCTGAGCGGGAGGTGCCGCTCTATGTGAACGGG
CCCCCCATCATCTCCAGTGAGGCAGTGCAGTATGCTGTGAGGGGTGACGGTGGCAAGGTGGAGTGTTT
CATTGGGAGCACACCACCCCCAGACCGCATAGCATGGGCCTGGAAGGAGAACTTCTTGGAGGTGGGGA
CCCTGGAACGCTATACAGTGGAGAGGACCAACTCAGGCAGTGGGGTGCTATCCACGCTCACCATCAAC
AATGTCATGGAGGCCGACTTTCAGACTCACTACAACTGCACCGCCTGGAACAGCTTCGGGCCAGGCAC
AGCCATCATCCAGCTGGAAGAGCGAGAGGTGTTACCTGTGGGCATCATAGCTGGGGCCACCATCGGCG
CGAGCATCCTGCTCATCTTCTTCTTCATCGCCTTGGTATTCTTCCTCTACCGGCGCCGCAAAGGCAGT
CGCAAAGACGTGACCCTGAGGAAGCTGGATATCAAGGTGGAGACAGTGAACCGAGAGCCACTTACGAT
GCATTCTGACCGGGAGGATGACACCGCCAGCGTCTCCACAGCAACCCGGGTCATGAAGGCCATCTACT
CGTCGTTTATGGATGATGTGGATCTGAAGCAGGACCTGCGCTGCGACACCATCGACACCCCGGAGGAG
TATGAGATGAAGGACCCCACCAATGGCTACTACAACGTGCGTGCCCATGAAGACCGCCCGTCTTCCAG
GGCAGTGCTCTATGCTGACTACCGTGCCCCTGGCCCTGCCCGCTTCGACGGCCGCCCCTCATCCCGTC
TCTCCCACTCCAGCGGCTATGCCCAGCTCAACACCTATAGCCGGGGCCCTGCCTCTGACTATGGCCCT
GAGCCCACACCCCCTGGCCCTGCTGCCCCAGCTGGCACTGACACAACCAGCCAGCTGTCCTACGAGAA
CTATGAGAAGTTCAACTCCCATCCCTTCCCTGGGGCAGCTGGGTACCCCACCTACCGACTGGGCTACC
CCCAGGCCCCACCCTCTGGCCTGGAGCGGACCCCATATGAGGCGTATGACCCCATTGGCAAGTACGCC
ACAGCCACTCGATTCTCCTACACCTCCCAGCACTCGGACTACGGCCAGCGATTCCAGCAGCGCATGCA
GACTCACGTGTAGGGGCCAG
NOV2g, CG51373-08
Protein Sequence	SEQ ID NO: 16	696 aa	MW at 76975.3kD
MGQGLKAWPRYRVVGSADAGQYNLEITDAELSDDASYECQATEAALRSRRAKLTVLIPPEDTRIDGGP
VILLQAGTPHNLTCRAFNAKPAATIIWFRDGTQQEGAVASTELLKDGKRETTVSQLLINPTDLDIGRV
FTCRSMNEAIPSGKETSIELDVHHPPTVTLSIEPQTVQEGERVVFTCQATANPEILDYRWAKGGFLIE
DAHESRYETNVDYSFFTEPVSCEVHNKVGSTNVSTLVNVHFAPRIVVDPKPTTTDIGSDVTLTCVWVG
NPPLTLTWTKKDSNMVLSNSNQLLLKSVTQADAGTYTCRAIVPRIGVAEREVPLYVNGPPIISSEAVQ
YAVRGDGGKVECFIGSTPPPDRIAWAWKENFLEVGTLERYTVERTNSGSGVLSTLTINNVMEADFQTH
YNCTAWNSFGPGTAIIQLEEREVLPVGIIAGATIGASILLIFFFIALVFFLYRRRKGSRKDVTLRKLD
IKVETVNREPLTMHSDREDDTASVSTATRVMKAIYSSFMDDVDLKQDLRCDTIDTREEYEMKDPTNGY
YNVRAHEDRPSSRAVLYADYRAPGPARFDGRPSSRLSHSSGYAQLNTYSRGPASDYGPEPTPPGPAAP
AGTDTTSQLSYENYEKFNSHPFPGAAGYPTYRLGYPQAPPSGLERTPYEAYDPIGKYATATRFSYTSQ
HSDYGQRFQQRMQTHV
NOV2h, CG51373-09	SEQ ID NO: 17	2128 bp
DNA Sequence	ORF Start: ATG at 31	ORF Stop: end of sequence
CAATGGACCAAGGACGGGCTGGCCCTGGGCATGGGCCAGGGCCTCAAAGCCTGGCCACGGTACCGGGT
TGTGGGCTCCGCAGACGCTGGGCAGTACAACCTGGAGATCACAGATGCTGAGCTCTCTGACGACGCCT
CTTACGAGTGCCAGGCCACGGAGGCCGCCCTGCGCTCTCGGCGGGCCAAACTCACCGTGCTCATCCCC
CCAGAGGACACCAGGATTGACGGAGGCCCTGTGATTCTACTGCAGGCAGGCACCCCCCACAACCTCAC
ATGCCGGGCCTTCAATGCGAAGCCTGCTGCCACCATCATCTGGTTCCGGGACGGGACGCAGCAGGAGG
GCGCTGTGGCCAGCACGGAATTGCTGAAGGATGGGAAGAGGGAGACCACCGTGAGCCAACTGCTTATT
AACCCCACGGACCTGGACATAGGGCGTGTCTTCACTTGCCGAAGCATGAACGAAGCCATCCCTAGTGG
CAAGGAGACTTCCATCGAGCTGGATGTGCACCACCCTCCTACAGTGACCCTGTCCATTGAGCCACAGA
CGGTGCAGGAGGGTGAGCGTGTTGTCTTTACCTGCCAGGCCACAGCCAACCCCGAGATCTTGGACTAC
AGGTGGGCCAAAGGGGGTTTCTTGATTGAAGACGCCCACGAGAGTCGCTATGAGACAAATGTGGATTA
TTCCTTTTTCACGGAGCCTGTGTCTTGTGAGGTTCACAACAAAGTGGGAAGCACCAATGTCAGCACTT
TAGTAAATGTCCACTTTGCTCCCCGGATTGTAGTTGACCCCAAACCCACAACCACAGACATTGGCTCT
GATGTGACCCTTACCTGTGTCTGGGTTGGGAATCCCCCCCTCACTCTCACCTCGACCAAAAAGGACTC
AAATATGGTCCTGAGTAACAGCAACCAGCTGCTGCTGAAGTCGGTCACTCAGGCAGACGCTGGCACCT
ACACCTGCCGGGCCATCGTGCCTCGAATCGGAGTGGCTGAGCGGGAGGTGCCGCTCTATGTGAACGGG
CCCCCCATCATCTCCAGTGAGGCAGTGCAGTATGCTGTGAGGGGTGACGGTGGCAAGGTGGAGTGTTT
CATTGGGAGCACACCACCCCCAGACCGCATAGCATGGGCCTGGAAGGAGAACTTCTTGGAGGTGGGGA
CCCTGGAACGCTATACAGTGGAGAGGACCAACTCAGGCAGTGGGGTGCTATCCACGCTCACCATCAAC
AATGTCATGGAGGCCGACTTTCAGACTCACTACAACTGCACCGCCTGGAACAGCTTCGGGCCAGGCAC
AGCCATCATCCAGCTGGAAGAGCGAGAGGTGTTACCTGTGGGCATCATAGCTGGGGCCACCATCGGCG
CGAGCATCCTGCTCATCTTCTTCTTCATCGCCTTGGTATTCTTCCTCTACCGGCGCCGCAAAGGCAGT
CGCAAAGACGTGACCCTGAGGAAGCTGGATATCAAGGTGGAGACAGTGAACCGAGAGCCACTTACGAT
GCATTCTGACCGGGAGGATGACACCGCCAGCGTCTCCACAGCAACCCGGGTCATGAAGGCCATCTACT
CGTCGTTTATGGATGATGTGGATCTGAAGCAGGACCTGCGCTGCGACACCATCGACACCCGGGAGGAG
TATGAGATGAAGGACCCCACCAATGGCTACTACAACGTGCGTGCCCATGAAGACCGCCCGTCTTCCAG
GGCAGTGCTCTATGCTGACTACCGTGCCCCTGGCCCTGCCCGCTTCGACGGCCGCCCCTCATCCCGTC
TCTCCCACTCCAGCGGCTATGCCCAGCTCAACACCTATAGCCGGGGCCCTGCCTCTGACTATGGCCCT
GAGCCCACACCCCCTGGCCCTGCTGCCCCAGCTGGCACTGACACAACCAGCCAGCTGTCCTACGAGAA
CTATGAGAAGTTCAACTCCCATCCCTTCCCTGGGGCAGCTGGGTACCCCACCTACCGACTGGGCTACC
CCCAGGCCCCACCCTCTGGCCTGGAGCGGACCCCATATGAGGCGTATGACCCCATTGGCAAGTACGCC
ACAGCCACTCGATTCTCCTACACCTCCCAGCACTCGGACTACGGCCAGCGATTCCAGCAGCGCATGCA
GACTCACGTGTAGGGGCCAG
NOV2h, CG51373-09
Protein Sequence	SEQ ID NO: 18	696 aa	MW at 76975.3kD
MGQGLKAWPRYRVVGSADAGQYNLEITDAELSDDASYECQATEAALRSRRAKLTVLIPPEDTRIDGGP
VILLQAGTPHNLTCRAFNAKPAATIIWFRDGTQQEGAVASTELLKDGKRETTVSQLLINPTDLDIGRV
FTCRSMNEAIPSGKETSIELDVHHPPTVTLSIEPQTVQEGERVVFTCQATANPEILDYRWAKGGFLIE
DAHESRYETNVDYSFFTEPVSCEVHNKVGSTNVSTLVNVHFAPRIVVDPKPTTTDIGSDVTLTCVWVG
NPPLTLTWTKKDSNMVLSNSNQLLLKSVTQADAGTYTCRAIVPRIGVAEREVPLYVNGPPIISSEAVQ
YAVRGDGGKVECFIGSTPPPDRIAWAWKENFLEVGTLERYTVERTNSGSGVLSTLTINNVMEADFQTH
YNCTAWNSFGPGTAIIQLEEREVLPVGIIAGATIGASILLIFFFIALVFFLYRRRKGSRKDVTLRKLD
IKVETVNREPLTMHSDREDDTASVSTATRVMKAIYSSFMDDVDLKQDLRCDTIDTREEYEMKDPTNGY
YNVRAHEDRPSSRAVLYADYRAPGPARFDGRPSSRLSHSSGYAQLNTYSRGPASDYGPEPTPPGPAAP
AGTDTTSQLSYENYEKFNSHPFPGAAGYPTYRLGYPQAPPSGLERTPYEAYDPIGKYATATRFSYTSQ
HSDYGQRFQQRMQTHV

[0380] Further analysis of the NOV2a protein yielded the following properties shown in Table 2H.

TABLE 2H
Protein Sequence Properties NOV2a
SignalP analysis:	No Known Signal Sequence Predicted
PSORT II analysis:
PSG:	a new signal peptide prediction method
	N-region: length 6; pos.chg 0; neg.chg 1
	H-region: length 25; peak value 0.00
	PSG score: −4.40
GvH:	von Heijne's method for signal seq. recognition
	GvH score (threshold: −2.1): −9.60
	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:  0
	number of TMS(s) . . . fixed
	PERIPHERAL Likelihood = 3.61 (at 122)
	ALOM score: 3.61 (number of TMSs: 0)
MITDISC: discrimination of mitochondrial targeting seq
	R content:	1	Hyd Moment(75):	5.49
	Hyd Moment(95):	8.44	G content:	3
	D/E Content:	2	S/T content:	5
	Score: −5.87
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: 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):
60.9%: cytoplasmic
26.1%: nuclear
8.7%: mitochondrial
4.3%: Golgi
>> prediction for CG51373-01 is cyt (k = 23)

[0381] PFam analysis predicts that the NOV2a protein contains the domains shown in the Table 21.

TABLE 2I
Domain Analysis of NOV2a
	NOV2a	Indentities/
	Match	Similarities
Pfam Domain	Region	for the Matched Region	Expect Value
ig	119 . . . 186	12/72 (17%)	1.9e−05
		46/72 (64%)
ig	220 . . . 286	14/69 (20%)	0.0023
		48/69 (70%)

Example 3. NOV 3, CG51514: Slit-3-like.

[0382] The NOV3 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 3A.

TABLE 3A
NOV3a Sequence Analysis
NOV3a, CG51514-01	SEQ ID NO: 19	1821 bp
DNA Sequence	ORF Start: ATG at 1	ORF Stop: end of sequence
ATGCTTCACACGGCCATATCATGCTGGCAGCCATTCCTGGGTCTGGCTGTGGTGTTAATCTTCATGGG
ATCCACCATTGGCTGCCCCGCTCGCTGTGAGTGCTCTGCCCAGAACAAATCTGTTAGCTGTCACAGAA
GGCGATTGATCGCCATCCCAGAGGGCATTCCCATCGAAACCAAAATCTTGGACCTCAGTAAAAACAGG
CTAAAAAGCGTCAACCCTGAAGAATTCATATCATATCCTCTGCTGGAAGAGATAGACTTGAGTGACAA
CATCATTGCCAATGTGGAACCAGGAGCATTCAACAATCTCTTTAACCTGCGTTCCCTCCGCCTAAAAG
GCAATCGTCTAAAGCTGGTCCCTTTGGGAGTATTCACGGGGCTGTCCAATCTCACTAAGCTTCACATT
AGTGAGAATAAGATTGTCATTTTACTAGACTACATGTTCCAAGATCTACATAACCTGAAGTCTCTAGA
AGTGGGGGACAATGATTTGGTTTATATATCACACAGGGCATTCAGTGGGCTTCTTAGCTTGGAGCAGC
TCACCCTGGAGAAATGCAACTTAACAGCAGTACCAACAGAAGCCCTCTCCCACCTCCGCAGCCTCATC
AGCCTGCATCTGAAGCATCTCAATATCAACAATATGCCTGTGTATGCCTTTAAAAGATTGTTCCACCT
GAAACACCTAGACATTGACTATTGGCCTTTACTGGATATGATGCCTGCCAATAGCCTCTACGGTCTCA
ACCTCACATCCCTTTCAGTCACCAACACCAATCTGTCTACTGTACCCTTCCTTGCCTTTAAACACCTG
GTATACCTGACTCACCTTAACCTCTCCTACAATCCCATCAGCACTATTGAAGCAGGCATGTTCTCTGA
CCTGATCCGCCTTCAGGAGCTTCATATAGTGGGGGCCCAGCTTCGCACCATTGAGCCTCACTCCTTCC
AAGGGCTCCGCTTCCTACGCGTGCTCAATGTGTCTCAGAACCTGCTGGAAACTTTGGAAGAGAATGTC
TTCTCCTCCCCTAGGGCTCTGGAGGTCTTGAGCATTAACAACAACCCTCTGGCCTGTGACTGCCGCCT
TCTCTGGATCTTGCAGCGACAGCCCACCCTGCAGTTTGGTGGCCAGCAACCTATGTGTGCTGGCCCAG
ACACCATCCGTGAGAGGTCTTTCAAGGATTTCCATAGCACTGCCCTTTCTTTTTACTTTACCTGCAAA
AAACCCAAAATCCGTGAAAAGAAGTTGCAGCATCTGCTAGTAGATGAAGGGCAGACAGTCCAGCTAGA
ATGCAGTGCAGATGGAGACCCGCAGCCTGTGATTTCCTGGGTGACACCCCGAAGGCGTTTCATCACCA
CCAAGTCCAATGGAAGAGCCACCGTGTTGGGTGATGCCACCTTGGAAATCCGCTTTGCCCAGGATCAA
GACAGCGGGATGTATGTTTGCATCGCTAGCAATGCTGCTGGGAATGATACCTTCACAGCCTCCTTAAC
TGTGAAAGGATTCGCTTCAGATCGTTTTCTTTATGCGAACAGGACCCCTATGTACATGACCGACTCCA
ATGACACCATTTCCAATGGCAGCAATGCCAATACTTTTTCCCTCGACCTTAAAACAATACTGGTGTCT
ACAGCTATGGGCTGCTTCACATTCCTGGGAGTGGTTTTATTTTGTTTTCTTCTCCTTTTTGTGTGGAG
CCGAGGGAAAGGCAAGCACAAAAACAGCATTGACCTTGAGTATGTGCCCAAAAAAAACCATGGTGCTG
TTGTGGAAGGGGAGGTAGCTGGACCCAGGAGGTTCAACATGAAAATGATTTGA
NOV3a, CG51514-01
Protein Sequence	SEQ ID NO: 20	606 aa	MW at 68046.0kD
MLHTAISCWQPFLGLAVVLIFMGSTIGCPARCECSAQNKSVSCHRRRLIAIPEGIPIETKILDLSKNR
LKSVNPEEFISYPLLEEIDLSDNIIANVEPGAFNNLFNLRSLRLKGNRLKLVPLGVFTGLSNLTKLDI
SENKIVILLDYMFQDLHNLKSLEVGDNDLVYISHRAFSGLLSLEQLTLEKCNLTAVPTEALSHLRSLI
SLHLKHLNINNMPVYAFKRLFHLKHLEIDYWPLLDMMPANSLYGLNLTSLSVTNTNLSTVPFLAFKHL
VYLTHLNLSYNPISTIEAGMFSDLIRLQELHIVGAQLRTIEPHSFQGLRFLRVLNSQNLLETLEENV
FSSPRALEVLSINNNPLACDCRLLWILQRQPTLQFGGQQPMCAGPDTIRERSFKDFHSTALSFYFTCK
KPKIREKKLQHLLVDEGQTVQLECSADGDPQPVISWVTPRRRFITTKSNGRATVLGDGTLEIRFAQDQ
DSGMYVCIASNAAGNDTFTASLTVKGFASDRFLYANRTPMYMTDSNDTISNGSNANTFSLDLKTILVS
TAMGCFTFLGVVLFCFLLLFVWSRGKGKHKNSIDLEYVPKKNHGAVVEGEVAGPRRFNMKMI

[0383] The NOV3b 13382215 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 3B.

TABLE 3B
NOV3b Sequence Analysis
NOV3b, 13382215	SEQ ID NO: 21	1821 bp
DNA Sequence	ORF Start: ATG at 1	ORF Stop: end of sequence
ATGCTTCACACGGCCATATCATGCTGGCAGCCATTCCTGGGTCTGGCTGTGGTGTTAATCTTCATGGG
ACCCACCATTGGCTGCCCCGCTCGCTGTGAGTGCTCTGCCCAGAACAAATCTGTTAGCTGTCACAGAA
GGCGATTGATCGCCATCCCAGAGGGCATTCCCATCGAAACCAAAATCTTGGACCTCAGTAAAAACAGG
CTAAAAAGCGTCAACCCTGAAGAATTCATATCATATCCTCTGCTGGAAGAGATAGACTTGAGTGACAA
CATCATTGCCAATGTGGAACCAGGAGCATTCAACAATCTCTTTAACCTGCGTTCCCTCCGCCTAAAAG
GCAATCGTCTAAAGCTGGTCCCTTTGGGAGTATTCACGGGGCTGTCCAATCTCACTAAGCTTGACATT
AGTGAGAATAAGATTGTCATTTTACTAGACTACATGTTCCAAGATCTACATAACCTGAAGTCTCTAGA
AGTGGGGGACAATGATTTGGTTTATATATCACACAGGGCATTCAGTGGGCTTCTTAGCTTGGAGCAGC
TCACCCTGGAGAAATGCAACTTAACAGCAGTACCAACAGAAGCCCTCTCCCACCTCCGCAGCCTCATC
AGCCTGCATCTGAAGCATCTCAATATCAACAATATGCCTGTGTATGCCTTTAAAAGATTGTTCCACCT
GAAACACCTAGAGATTGACTATTGGCCTTTACTGGATATGATGCCTGCCAATAGCCTCTACGGTCTCA
ACCTCACATCCCTTTCAGTCACCAACACCAATCTGTCTACTGTACCCTTCCTTGCCTTTAAACACCTG
GTATACCTGACTCACCTTAACCTCTCCTACAATCCCATCAGCACTATTGAAGCAGGCATGTTCTCTGA
CCTGATCCGCCTTCAGGAGCTTCATATAGTGGGGGCCCAGCTTCGCACCATTGAGCCTCACTCCTTCC
AAGGGCTCCGCTTCCTACGCGTGCTCAATGTGTCTCAGAACCTGCTGGAAACTTTGGAAGAGAATGTC
TTCTCCTCCCCTAGGGCTCTGGAGGTCTTGAGCATTAACAACAACCCTCTGGCCTGTGACTGCCGCCT
TCTCTGGATCTTGCAGCGACAGCCCACCCTGCAGTTTGGTGGCCAGCAACCTATGTGTGCTGGCCCAG
ACACCATCCGTGAGACGTCTTTCAAGGATTTCCATAGCACTGCCCTTTCTTTTTACTTTACCTGCAAA
AAACCCAAAATCCGTGAAAAGAAGTTGCAGCATCTGCTAGTAGATGAAGGGCAGACAGTCCAGCTAGA
ATGCAGTGCAGATGGAGACCCGCAGCCTGTGATTTCCTGGGTGACACCCCGAAGGCGTTTCATCACCA
CCAAGTCCAATGGAAGAGCCACCGTGTTGGGTGATGGCACCTTGGAAATCCGCTTTGCCCAGGATCAA
GACAGCGGGATGTATGTTTGCATCGCTAGCAATGCTGCTGGGAATGATACCTTCACAGCCTCCTTAAC
TGTGAAAGGATTCGCTTCAGATCGTTTTCTTTATGCGAACAGGACCCCTATGTACATGACCGACTCCA
ATGACACCATTTCCAATGGCAGCAATGCCAATACTTTTTCCCTGGACCTTAAAACAATACTGGTGTCT
ACAGCTATGGGCTGCTTCACATTCCTGGGAGTGGTTTTATTTTGTTTTCTTCTCCTTTTTGTGTGGAG
CCGAGGGAAAGGCAAGCACAAAAACAGCATTGACCTTGAGTATGTGCCCAAAAAAAACCATGGTGCTG
TTGTGGAAGGGGAGGTAGCTGGACCCAGGAGGTTCAACATGAAAATGATTTGA
NOV3b, 13382215
Protein Sequence	SEQ ID NO: 22	606 aa	MW at 68046.0kD
MLHTAISCWQPFLGLAVVLIFMGPTIGCPARCECSAQNKSVSCHRRRLIAIPEGIPIETKILDLSKNR
LKSVNPEEFISYPLLEEIDLSDNIIANVEPGAFNNLFNLRSLRLKGNRLKLVPLGVFTGLSNLTKLDI
SENKIVILLDYMFQDLHNLKSLEVGDNDLVYISHRAFSGLLSLEQLTLEKCNLTAVPTEALSHLRSLI
SLHLKHLNINNMPVYAFKRLFHLKHLEIDYWPLLDMMPANSLYGLNLTSLSVTNTNLSTVPFLAFKHL
VYLTHLNLSYNPISTIEAGMFSDLIRLQELHIVGAQLRTIEPHSFQGLRFLRVLNVSQNLLETLEENV
FSSPRALEVLSINNNPLACDCRLLWILQRQPTLQFGGQQPMCAGPDTIRERSFKDFHSTALSFYFTCK
KPKIREKKLQHLLVDEGQTVQLECSADGDPQPVISWVTPRRRFITTKSNGRATVLGDGTLEIRFAQDQ
DSGMYVCIASNAAGNDTFTASLTVKGFASDRFLYANRTPMYMTDSNDTISNGSNANTFSLDLKTILVS
TAMGCFTFLGVVLFCFLLLFVWSRGKGKHKNSIDLEYVPKKNHGAVVEGEVAGPRRFNMKMI

[0384] The NOV3c clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 3C.

TABLE 3C
NOV3c Sequence Analysis
NOV3c, 13375162	SEQ ID NO: 23	1821 bp
DNA Sequence	ORF Start: ATG at 1	ORF Stop: end of the sequence
ATGCTTCACACGGCCATATCATGCTGGCAGCCATTCCTGGGTCTGGCTGTGGTGTTAATCTTCATGGG
ATCCACCATTGGCTGCCCCGCTCGCTGTGAGTGCTCTGCCCAGAACAAATCTGTTAGCTGTCACAGAA
GGCGATTGATCGCCATCCCAGAGGGCATTCCCATCGAAACCAAAATCTTGAACCTCAGTAAAAACAGG
CTAAAAAGCGTCAACCCTGAAGAATTCATATCATATCCTCTGCTGGAAGAGATAGACTTGAGTGACAA
CATCATTGCCAATGTGGAACCAGGAGCATTCAACAATCTCTTTAACCTGCGTTCCCTCCGCCTAAAAG
GCAATCGTCTAAAGCTGGTCCCTTTGGGAGTATTCACGGGGCTGTCCAATCTCACTAAGCTTGACATT
AGTGAGAATAAGATTGTCATTTTACTAGACTACATGTTCCAAGATCTACATAACCTGAAGTCTCTAGA
AGTGGGGGACAATGATTTGGTTTATATATCACACAGGCCATTCAGTGGGCTTCTTAGCTTGGAGCAGC
TCACCCTGGAGAAATGCAACTTAACAGCAGTACCAACAGAAGCCCTCTCCCACCTCCGCAGCCTCATC
AGCCTGCATCTGAAGCATCTCAATATCAACAATATGCCTGTGTATGCCTTTAAAAGATTGTTCCACCT
GAAACACCTAGAGATTGACTATTGGCCTTTACTGGATATGATGCCTGCCAATAGCCTCTACGGTCTCA
ACCTCACATCCCTTTCAGTCACCAACACCAATCTGTCTACTGTACCCTTCCTTGCCTTTAAACACCTG
GTATACCTGACTCACCTTAACCTCTCCTACAATCCCATCAGCACTATTGAAGCAGGCATGTTCTCTGA
CCTGATCCGCCTTCAGGAGCTTCATATAGTGGGGGCCCAGCTTCGCACCATTGAGCCTCACTCCTTCC
AAGGGCTCCGCTTCCTACGCGTGCTCAATGTGTCTCAGAACCTGCTGGAAACTTTGGAAGAGAATGTC
TTCTCCTCCCCTAGGGCTCTGGAGGTCTTGAGCATTAACAACAACCCTCTGGCCTGTGACTGCCGCCT
TCTCTGGATCTTGCAGCGACAGCCCACCCTGCAGTTTGGTGGCCAGCAACCTATGTGTGCTGGCCCAG
ACACCATCCGTGAGAGGTCTTTCAAGGATTTCCATAGCACTGCCCTTTCTTTTTACTTTACCTGCAAA
AAACCCAAAATCCGTGAAAAGAAGTTGCAGCATCTGCTAGTAGATGAAGGGCAGACAGTCCAGCTAGA
ATGCAGTGCAGATGGAGACCCGCAGCCTGTGATTTCCTGGGTGACACCCCGAAGGCGTTTCATCACCA
CCAAGTCCAATGGAAGAGCCACCGTGTTGGGTGATGGCACCTTGGAAATCCGCTTTGCCCAGGATCAA
GACAGCGGGATGTATGTTTGCATCGCTAGCAATGCTGCTGGGAATGATACCTTCACAGCCTCCTTAAC
TGTGAAAGGATTCGCTTCAGATCGTTTTCTTTATGCGAACAGGACCCCTATGTACATGACCGACTCCA
ATGACACCATTTCCAATGGCAGCAATGCCAATACTTTTTCCCTGGACCTTAAAACAATACTGGTGTCT
ACAGCTATGGGCTGCTTCACATTCCTGGGAGTGGTTTTATTTTGTTTTCTTCTCCTTTTTGTGTGGAG
CCGAGGGAAAGGCAAGCACAAAAACAGCATTGACCTTGAGTATGTGCCCAAAAAAAACCATGGTGCTG
TTGTGGAAGGGGAGGTAGCTGGACCCAGGAGGTTCAACATGAAAATGATTTGA
NOV3c, 13375162
Protein Sequence	SEQ ID NO: 24	606 aa	MW at 68046.0kD
MLHTAISCWQPFLGLAVVLIFMGSTIGCPARCECSAQNKSVSCHRRRLIAIPEGIPIETKILNLSKNR
LKSVNPEEFISYPLLEEIDLSDNIIANVEPGAFNNLFNLRSLRLKGNRLKLVPLGVFTGLSNLTKLDI
SENKIVILLDYMFQDLHNLKSLEVGDNDLVYISHRAFSGLLSLEQLTLEKCNLTAVPTEALSHLRSLI
SLHLKHLNINNMPVYAFKRLFHLKHLEIDYWPLLDMMPANSLYGLNLTSLSVTNTNLSTVPFLAFKHL
VYLTHLNLSYNPISTIEAGMFSDLIRLQELHIVGAQLRTIEPHSFQGLRFLRVLNVSQNLLETLEENV
FSSPRALEVLSINNNPLACDCRLLWILQRQPTLQFGGQQPMCAGPDTIRERSFKDFHSTALSFYFTCK
KPKIREKKLQHLLVDEGQTVQLECSADGDPQPVISWVTPRRRFITTKSNGRATVLGDGTLEIRFAQDQ
DSGMYVCIASNAAGNDTFTASLTVKGFASDRFLYANRTPMYMTDSNDTISNGSNANTFSLDLKTILVS
TAMGCFTFLGVVLFCFLLLFVWSRGKGKHKNSIDLEYVPKKNHGAVVEGEVAGPRRFNMKMI

[0385] The NOV3d 13374269 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 3D.

TABLE 3D
NOV3d Sequence Analysis
NOV3d, 13374269	SEQ ID NO: 25	1821 bp
DNA Sequence	ORF Start: ATG at 1	ORF Stop: end of sequence
ATGCTTCACACGGCCATATCATGCTGGCAGCCATTCCTGGGTCTGGCTGTGGTGTTAATCTTCATGGG
ATCCACCATTGGCTGCCCCGCTCGCTGTGAGTGCTCTCCCCAGAACAAATCTGTTAGCTGTCACAGAA
GGCGATTGATCGCCATCCCAGAGGGCATTCCCATCGAAACCAAAATCTTGGACCTCAGTAAAAACAGG
CTAAAAAGCGTCAACCCTGAAGAATTCATATCATATCCTCTGCTGGAAGAGATAGACTTGAGTGACAA
CATCATTGCCAATGTGGAACCAGGAGCATTCAACAATCTCTTTAACCTGCGTTCCCTCCGCCTAAAAG
GCAATCGTCTAAAGCTGGTCCCTTTGGGAGTATTCACGGGGCTGTCCAGTCTCACTAAGCTTGACATT
AGTGAGAATAAGATTGTCATTTTACTAGACTACATGTTCCAAGATCTACATAACCTGAAGTCTCTAGA
AGTGGGGGACAATGATTTGGTTTATATATCACACAGGGCATTCAGTGGGCTTCTTAGCTTGGAGCAGC
TCACCCTGGAGAAATGCAACTTAACAGCAGTACCAACAGAACCCCTCTCCCACCTCCGCAGCCTCATC
AGCCTGCATCTGAAGCATCTCAATATCAACAATATGCCTGTGTATGCCTTTAAAAGATTGTTCCACCT
GAAACACCTAGAGATTGACTATTGGCCTTTACTGGATATGATGCCTGCCAATAGCCTCTACGGTCTCA
ACCTCACATCCCTTTCAGTCACCAACACCAATCTGTCTACTGTACCCTTCCTTGCCTTTAAACACCTG
GTATACCTGACTCACCTTAACCTCTCCTACAATCCCATCAGCACTATTGAAGCAGGCATGTTCTCTGA
CCTGATCCGCCTTCAGGAGCTTCATATAGTGGGGGCCCAGCTTCGCACCATTGAGCCTCACTCCTTCC
AAGGGCTCCGCTTCCTACGCGTGCTCAATGTGTCTCAGAACCTGCTGGAAACTTTGGAAGAGAATGTC
TTCTCCTCCCCTAGGGCTCTGGAGGTCTTGAGCATTAACAACAACCCTCTGGCCTGTGACTGCCGCCT
TCTCTGGATCTTGCAGCGACAGCCCACCCTGCAGTTTGGTGGCCAGCAACCTATGTGTGCTGGCCCAG
ACACCATCCGTGAGAGGTCTTTCAAGGATTTCCATAGCACTGCCCTTTCTTTTTACTTTACCTGCAAA
AAACCCAAAATCCGTGAAAAGAAGTTGCAGCATCTGCTAGTAGATGAAGGGCAGACAGTCCAGCTAGA
ATGCAGTGCAGATGGAGACCCGCAGCCTGTGATTTCCTGGGTGACACCCCGAAGGCGTTTCATCACCA
CCAAGTCCAATGGAAGAGCCACCGTGTTGGGTGATGGCACCTTGGAAATCCGCTTTGCCCAGGATCAA
GACAGCGGGATGTATGTTTGCATCGCTAGCAATGCTGCTGGGAATGATACCTTCACAGCCTCCTTAAC
TGTGAAAGGATTCGCTTCAGATCGTTTTCTTTATGCGAACAGGACCCCTATGTACATGACCGACTCCA
ATGACACCATTTCCAATGGCAGCAATGCCAATACTTTTTCCCTGGACCTTAAAACAATACTGGTGTCT
ACAGCTATGGGCTGCTTCACATTCCTGGGAGTGGTTTTATTTTGTTTTCTTCTCCTTTTTGTGTGGAG
CCGAGGGAAAGGCAAGCACAAAAACAGCATTGACCTTGAGTATGTGCCCAAAAAAAACCATGGTGCTG
TTGTGGAAGGGGAGGTAGCTGGACCCAGGAGGTTCAACATGAAAATGATTTGA
NOV3d, 13374269
Protein Sequence	SEQ ID NO: 26	606 aa	MW at 68046.0kD
MLHTAISCWQPFLGLAVVLIFMGSTIGCPARCECSAQNKSVSCHRRRLIAIPEGIPIETKILDLSKNR
LKSVNPEEFISYPLLEEIDLSDNIIANVEPGAFNNLFNLRSLRLKGNRLKLVPLGVFTGLSSLTKLDI
SENKIVILLDYMFQDLHNLKSLEVGDNDLVYISHRAFSGLLSLEQLTLEKCNLTAVPTEALSHLRSLI
SLHLKHLNINNMPVYAFKRLFHLKHLEIDYWPLLDMMPANSLYGLNLTSLSVTNTNLSTVPFLAFKHL
VYLTHLNLSYNPISTIEAGMFSDLIRLQELHIVGAQLRTIEPHSFQGLRFLRVLNVSQNLLETLEENV
FSSPRALEVLSINNNPLACDCRLLWILQRQPTLQFGGQQPMCAGPDTIRERSFKDFHSTALSFYFTCK
KPKIREKKLQHLLVDEGQTVQLECSADGDPQPVISWVTPRRRFITTKSNGRATVLGDGTLEIRFAQDQ
DSGMYVCIASNAAGNDTFTASLTVKGFASDRFLYANRTPMYMTDSNDTISNGSNANTFSLDLKTILVS
TAMGCFTFLGVVLFCFLLLFVWSRGKGKHKNSIDLEYVPKKNHGAVVEGEVAGPRRFNMKMI

[0386] The NOV3e 13375297clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 3E.

TABLE 3E
NOV3e Sequence Analysis
NOV3e, 13375297	SEQ ID NO: 27	1821 bp
DNA Sequence	ORF Start: ATG at 1	ORF Stop: end of sequence
ATGCTTCACACGGCCATATCATGCTGGCAGCCATTCCTGGGTCTGGCTGTGGTGTTAATCTTCATGGG
ATCCACCATTGGCTGCCCCGCTCGCTGTGAGTGCTCTGCCCAGAACAAATCTGTTAGCTGTCACAGAA
GGCGATTGATCGCCATCCCAGAGGGCATTCCCATCGAAACCAAAATCTTGGACCTCAGTAAAAACAGG
CTAAAAAGCGTCAACCCTGAAGAATTCATATCATATCCTCTGCTGGAAGAGATAGACTTGAGTGACAA
CATCATTGCCAATGTGGAACCAGGAGCATTCAACAATCTCTTTAACCTGCGTTCCCTCCGCCTAAAAG
GCAATCGTCTAAAGCTGGTCCCTTTGGGAGTATTCACGGGGCTGTCCAATCTCACTAAGCTTGACATT
AGTGAGAATAAGATTGTCATTTTACTAGACTACATGTTCCAAGATCTACATAACCTGAAGTCTCTAGA
AGTGGGGGACAATGATTTGGTTTATATATCACACAGGGCATTCAGTGGGCTTCTTAGCTTGGAGCAGC
TCACCCTGGAGAAATGCAACTTAACAGCAGTACCAACACAAGCCCTCTCCCACCTCCGCAGCCTCATC
AGCCTGCATCTGAAGCATCTCAATATCAACAATATGCCTGTGTATACCTTTAAAAGATTGTTCCACCT
GAAACACCTAGAGATTGACTATTGGCCTTTACTGGATATGATGCCTGCCAATAGCCTCTACGGTCTCA
ACCTCACATCCCTTTCAGTCACCAACACCAATCTGTCTACTGTACCCTTCCTTGCCTTTAAACACCTG
GTATACCTGACTCACCTTAACCTCTCCTACAATCCCATCAGCACTATTGAAGCAGGCATGTTCTCTGA
CCTGATCCGCCTTCAGGAGCTTCATATAGTGGGGGCCCAGCTTCGCACCATTGAGCCTCACTCCTTCC
AAGGGCTCCGCTTCCTACGCGTGCTCAATCTGTCTCAGAACCTGCTGGAAACTTTGGAAGAGAATGTC
TTCTCCTCCCCTAGGGCTCTGGAGGTCTTGAGCATTAACAACAACCCTCTGGCCTGTGACTGCCGCCT
TCTCTGGATCTTGCAGCGACAGCCCACCCTGCAGTTTGGTGGCCAGCAACCTATGTGTGCTGGCCCAG
ACACCATCCGTGAGAGGTCTTTCAAGGATTTCCATAGCACTGCCCTTTCTTTTTACTTTACCTGCAAA
AAACCCAAAATCCGTGAAAAGAAGTTGCAGCATCTGCTAGTAGATGAAGGGCAGACAGTCCAGCTAGA
ATGCAGTGCAGATGGAGACCCGCAGCCTGTGATTTCCTGGGTGACACCCCGAAGGCGTTTCATCACCA
CCAAGTCCAATGGAAGAGCCACCGTGTTGGGTGATGGCACCTTGGAAATCCGCTTTGCCCAGGATCAA
GACAGCGGGATGTATGTTTGCATCGCTAGCAATGCTGCTGGGAATGATACCTTCACAGCCTCCTTAAC
TGTGAAAGGATTCGCTTCAGATCGTTTTCTTTATGCGAACAGGACCCCTATGTACATGACCGACTCCA
ATGACACCATTTCCAATGGCAGCAATGCCAATACTTTTTCCCTGGACCTTAAAACAATACTGGTGTCT
ACAGCTATGGGCTGCTTCACATTCCTGGGAGTGGTTTTATTTTGTTTTCTTCTCCTTTTTGTGTGGAG
CCGAGGGAAAGGCAAGCACAAAAACAGCATTGACCTTGAGTATGTGCCCAAAAAAAACCATGGTGCTG
TTGTGGAAGGGGAGGTAGCTGGACCCAGGAGGTTCAACATGAAAATGATTTGA
NOV3e, 13375297
Protein Sequence	SEQ ID NO: 28	606 aa	MW at 68046.0kD
MLHTAISCWQPFLGLAVVLIFMGSTIGCPARCECSAQNKSVSCHRRRLIAIPEGIPIETKILDLSKNR
LKSVNPEEFISYPLLEEIDLSDNIIANVEPGAFNNLFNLRSLRLKGNRLKLVPLGVFTGLSNLTKLDI
SENKIVILLDYMFQDLHNLKSLEVGDNDLVYISHRAFSGLLSLEQLTLEKCNLTAVPTEALSHLRSLI
SLHLKHLNINNMPVYTFKRLFHLKHLEIDYWPLLDMMPANSLYGLNLTSLSVTNTNLSTVPFLAFKHL
VYLTHLNLSYNPISTIEAGMFSDLIRLQELHIVGAQLRTIEPHSFQGLRFLRVLNVSQNLLETLEENV
FSSPRALEVLSINNNPLACDCRLLWILQRQPTLQFGGQQPMCAGPDTIRERSFKDFHSTALSFYFTCK
KPKIREKKLQHLLVDEGQTVQLECSADGDPQPVISWVTPRRRFITTKSNGRATVLGDGTLEIRFAQDQ
DSGMYVCIASNAAGNDTFTASLTVKGFASDRFLYANRTPMYMTDSNDTISNGSNANTFSLDLKTILVS
TAMGCFTFLGVVLFCFLLLFVWSRGKGKHKNSIDLEYVPKKNHGAVVEGEVAGPRRFNMKMI

[0387] The NOV3f 13375298 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 3F.

TABLE 3F
NOV3f Sequence Analysis
NOV3f,13375298	SEQ ID NO: 29	1821 bp
DNA Sequence	ORF Start: ATG at 1	ORF Stop: end of sequence
ATGCTTCACACGGCCATATCATGCTGGCAGCCATTCCTGGGTCTGGCTGTGGTGTTAATCTTCATGGG
ATCCACCATTGGCTGCCCCGCTCGCTGTGAGTGCTCTGCCCAGAACAAATCTGTTAGCTGTCACAGAA
GGCGATTGATCGCCATCCCAGAGGGCATTCCCATCGAAACCAAAATCTTGGACCTCAGTAAAAACAGG
CTAAAAAGCGTCAACCCTGAAGAATTCATATCATATCCTCTGCTGGAAGAGATAGACTTGAGTGACAA
CATCATTGCCAATGTGGAACCAGGAGCATTCAACAATCTCTTTAACCTGCGTTCCCTCCGCCTAAAAG
GCAATCGTCTAAAGCTGGTCCCTTTGGGAGTATTCACGGGGCTGTCCAATCTCACTAAGCTTGACATT
AGTGAGAATAAGATTGTCATTTTACTAGACTACATGTTCCAAGATCTACATAACCTGAAGTCTCTAGA
AGTGGGGGACAATGATTTGGTTTATATATCACACAGGGCATTCAGTGGGCTTCTTAGCTTGGAGCAGC
TCACCCTGGAGAAATGCAACTTAACAGCAGTACCAACAGAAGCCCTCTCCCACCTCCGCAGCCTCATC
AGCCTGCATCTGAAGCATCTCAATATCAACAATATGCCTGTGTATGCCTTTAAAAGATTGTTCCACCT
GAAACACCTAGAGATTGACTATTGGCCTTTACTGGATATGATGCCTGCCAATAGCCTCTACGGTCTCA
ACCTCACACCCCTTTCAGTCACCAACACCAATCTGTCTACTGTACCCTTCCTTGCCTTTAAACACCTG
GTATACCTGACTCACCTTAACCTCTCCTACAATCCCATCAGCACTATTGAAGCAGGCATGTTCTCTGA
CCTGATCCGCCTTCAGGAGCTTCATATAGTGGGGGCCCAGCTTCGCACCATTGAGCCTCACTCCTTCC
AAGGGCTCCGCTTCCTACGCGTGCTCAATGTGTCTCAGAACCTGCTGGAAACTTTGGAAGAGAATGTC
TTCTCCTCCCCTAGGGCTCTGGAGGTCTTGAGCATTAACAACAACCCTCTGGCCTGTGACTGCCGCCT
TCTCTGGATCTTGCAGCGACAGCCCACCCTGCAGTTTGGTGGCCAGCAACCTATGTGTGCTGGCCCAG
ACACCATCCGTGAGAGGTCTTTCAAGGATTTCCATAGCACTGCCCTTTCTTTTTACTTTACCTGCAAA
AAACCCAAAATCCGTGAAAAGAAGTTGCAGCATCTGCTAGTAGATGAAGCGCAGACAGTCCAGCTAGA
ATGCAGTGCAGATGGAGACCCGCAGCCTGTGATTTCCTGGGTGACACCCCGAAGGCGTTTCATCACCA
CCAAGTCCAATGGAAGAGCCACCGTGTTGGGTGATGGCACCTTGGAAATCCGCTTTGCCCAGGATCAA
GACAGCGGGATGTATGTTTGCATCGCTAGCAATGCTGCTGGGAATGATACCTTCACAGCCTCCTTAAC
TGTGAAAGGATTCGCTTCAGATCGTTTTCTTTATGCGAACAGGACCCCTATGTACATGACCGACTCCA
ATGACACCATTTCCAATGGCAGCAATGCCAATACTTTTTCCCTGGACCTTAAAACAATACTGGTGTCT
ACAGCTATGGGCTGCTTCACATTCCTGGGAGTGGTTTTATTTTGTTTTCTTCTCCTTTTTGTGTGGAG
CCGAGGGAAAGGCAAGCACAAAAACAGCATTGACCTTGAGTATGTGCCCAAAAAAAACCATGGTGCTG
TTGTGGAAGGGGAGGTAGCTGGACCCAGGAGGTTCAACATGAAAATGATTTGA
NOV3f, 13375298
Protein Sequence	SEQ ID NO: 30	606 aa	MW at 68046.0kD
MLHTAISCWQPFLGLAVVLIFMGSTIGCPARCECSAQNKSVSCHRRRLIAIPEGIPIETKILDLSKNR
LKSVNPEEFISYPLLEEIDLSDNIIANVEPGAFNNLFNLRSLRLKGNRLKLVPLGVFTGLSNLTKLDI
SENKIVILLDYMFQDLHNLKSLEVGDNDLVYISHRAFSGLLSLEQLTLEKCNLTAVPTEALSHLRSLI
SLHLKHLNINNMPVYAFKRLFHLKRLEIDYWPLLDMMPANSLYGLNLTPLSVTNTNLSTVPFLAFKHL
VYLTHLNLSYNPISTIEAGMFSDLIRLQELHIVGAQLRTIEPHSFQGLRFLRVLNVSQNLLETLEENV
FSSPRALEVLSINNNPLACDCRLLWILQRQPTLQFGGQQPMCAGPDTIRERSFKDFHSTALSFYFTCK
KPKIREKKLQHLLVDEGQTVQLECSADGDPQPVISWVTPRRRFITTKSNGRATVLGDGTLEIRFAQDQ
DSGMYVCIASNAAGNDTFTASLTVKGFASDRFLYANRTPMYMTDSNDTISNGSNANTFSLDLKTILVS
TAMGCFTFLGVVLFCFLLLFVWSRGKGKHKNSIDLEYVPKKNHGAVVEGEVAGPRRFNMKMI

[0388] The NOV3g 13375299 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 3G.

TABLE 3G
NOV3g Sequence Analysis
NOV3g, 13375299	SEQ ID NO: 31	1821 bp
DNA Sequence	ORF Start: ATG at 1	ORF Stop: end of sequence
ATGCTTCACACGGCCATATCATGCTGGCAGCCATTCCTGGGTCTGGCTGTGGTGTTAATCTTCATGGG
ATCCACCATTGCCTGCCCCGCTCGCTGTGAGTGCTCTGCCCAGAACAAATCTGTTAGCTGTCACAGAA
GGCGATTGATCGCCATCCCAGAGGGCATTCCCATCGAAACCAAAATCTTGGACCTCAGTAAAAACAGG
CTAAAAAGCGTCAACCCTGAAGAATTCATATCATATCCTCTGCTGGAAGAGATAGACTTGAGTGACAA
CATCATTGCCAATGTGGAACCAGGAGCATTCAACAATCTCTTTAACCTGCGTTCCCTCCGCCTAAAAG
GCAATCGTCTAAAGCTGGTCCCTTTGGGAGTATTCACGGGGCTGTCCAATCTCACTAAGCTTGACATT
AGTGAGAATAAGATTGTCATTTTACTAGACTACATGTTCCAAGATCTACATAACCTGAAGTCTCTAGA
AGTGGGGGACAATGATTTGGTTTATATATCACACAGGGCATTCAGTGGGCTTCTTAGCTTGGAGCAGC
TCACCCTGGAGAAATGCAACTTAACAGCAGTACCAACAGAAGCCCTCTCCCACCTCCGCAGCCTCATC
AGCCTGCATCTGAAGCATCTCAATATCAACAATATGCCTGTGTATGCCTTTAAAAGATTGTTCCACCT
GAAACACCTAGAGATTGACTATTGGCCTTTACTGGATATGATGCCTGCCAATAGCCTCTACGGTCTCA
ACCTCACATCCCTTTCAGTCACCAACACCAATCTGTCTACTGTACCCTTCCTTGCCTTTAAACACCTG
GTATACCTGACTCACCTTAACCTCTCCTACAATCCCATCAGCACTATTGAAGCAGGCATGTTCTCTGA
CCTGATCCGCCTTCAGGAGCTTCATATAGTGGGGGCCCAGCTTCGCACCATTGAGCCTCACTCCTTCC
AAGGGCTCCGCTTCCTACGCGTGCTCAATGTGTCTCAGAACCTGCTGGAAACTTTGGAAGAGAATGTC
TTCTCCTCCCCTAGGGCTCTGGAGGTCTTGAGCATTAACAACAACCCTCTGGCCTGTGACTGCCGCCT
TCTCTGGATCTTGCAGCGACAGCCCACCCTGCAGTTTGGTGGCCAGCAACCTATGTGTGCTGGCCCAG
ACACCATCCGTGAGAGGTCTTTCAAGGATTTCCATAGCACTGCCCTTTCTTTTTACTTTACCTGCAAA
AAACCCAAAATCCGTGAAAAGAAGTTGCAGCATCTGCTAGTAGATGAAGGGCAGACAGTCCAGCTAGA
ATGCAGTGCAGATGGAGACCCGCAGCCTGTGATTTCCTGGGTGACACCCCGAAGGCGTTTCATCACCA
CCAAGTCCAATGGAAGAGTCACCGTGTTGGGTGATGGCACCTTGGAAATCCGCTTTGCCCAGGATCAA
GACAGCGGGATGTATGTTTGCATCGCTAGCAATGCTGCTGGGAATGATACCTTCACAGCCTCCTTAAC
TGTGAAAGGATTCGCTTCAGATCGTTTTCTTTATGCGAACAGGACCCCTATGTACATGACCGACTCCA
ATGACACCATTTCCAATGGCAGCAATGCCAATACTTTTTCCCTGGACCTTAAAACAATACTGGTGTCT
ACAGCTATGGGCTGCTTCACATTCCTGGGAGTGGTTTTATTTTGTTTTCTTCTCCTTTTTGTGTGGAG
CCGAGGGAAAGGCAAGCACAAAAACAGCATTGACCTTGAGTATGTGCCCAAAAAAAACCATGGTGCTG
TTGTGGAAGGGGAGGTAGCTGGACCCAGGAGGTTCAACATGAAAATGATTTGA
NOV3g, 13375299
Protein Sequence	SEQ ID NO: 32	606 aa	MW at 68046.0kD
MLHTAISCWQPFLGLAVVLIFMGSTIGCPARCECSAQNKSVSCHRRRLIAIPEGIPIETKILDLSKNR
LKSVNPEEFISYPLLEEIDLSDNIIANVEPGAFNNLFNLRSLRLKGNRLKLVPLGVFTGLSNLTKLDI
SENKIVILLDYMFQDLHNLKSLEVGDNDLVYISHRAFSGLLSLEQLTLEKCNLTAVPTEALSHLRSLI
SLHLKHLNINNMPVYAFKRLFHLKHLEIDYWPLLDMMPANSLYGLNLTSLSVTNTNLSTVPFLAFKHL
VYLTHLNLSYNPISTIEAGMFSDLIRLQELHIVGAQLRTIEPHSFQGLRFLRVLNVSQNLLETLEENV
FSSPRALEVLSINNNPLACDCRLLWILQRQPTLQFGGQQPMCAGPDTIRERSFKDFHSTALSFYFTCK
KPKIREKKLQHLLVDEGQTVQLECSADGDPQPVISWVTPRRRFITTKSNGRVTVLGDGTLEIRFAQDQ
DSGMYVCIASNAAGNDTFTASLTVKGFASDRFLYANRTPMYMTDSNDTISNGSNANTFSLDLKTILVS
TAMGCFTFLGVVLFCFLLLFVWSRGKGKHKNSIDLEYVPKKNHGAVVEGEVAGPRRFNMKMI

[0389] The NOV3h CG51514-02 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 3H.

TABLE 3H
NOV3h, CG51514-02	SEQ ID NO: 33	1737 bp
DNA Sequence	ORF Start: at 1	ORF Stop: end of sequence
TGCCCCGCTCGCTGTGAGTGCTCTGCCCAGAACAAATCTGTTAGCTGTCACAGAAGGCGATTGATCGC
CATCCCAGAGGGCATTCCCATCGAAACCAAAATCTTGGACCTCAGTAAAAACAGGCTAAAAAGCGTCA
ACCCTGAAGAATTCATATCATATCCTCTGCTGGAAGAGATAGACTTGAGTGACAACATCATTGCCAAT
GTGGAACCAGGAGCATTCAACAATCTCTTTAACCTGCGTTCCCTCCGCCTAAAAGGCAATCGTCTAAA
GCTGGTCCCTTTGGGAGTATTCACGGGGCTGTCCAATCTCACTAAGCTTGACATTAGTGAGAATAAGA
TTGTCATTTTACTAGACTACATGTTCCAAGATCTACATAACCTGAAGTCTCTAGAAGTGGGGGACAAT
GATTTGGTTTATATATCACACAGGGCATTCAGTGGGCTTCTTAGCTTGGAGCAGCTCACCCTGGAGAA
ATGCAACTTAACAGCAGTACCAACAGAAGCCCTCTCCCACCTCCGCAGCCTCATCAGCCTGCATCTGA
AGCATCTCAATATCAACAATATGCCTGTGTATGCCTTTAAAAGATTGTTCCACCTGAAACACCTAGAG
ATTGACTATTGGCCTTTACTGGATATGATGCCTGCCAATAGCCTCTACGGTCTCAACCTCACATCCCT
TTCAGTCACCAACACCAATCTGTCTACTGTACCCTTCCTTGCCTTTAAACACCTGGTATACCTGACTC
ACCTTAACCTCTCCTACAATCCCATCAGCACTATTGAAGCAGGCATGTTCTCTGACCTGATCCGCCTT
CAGGAGCTTCATATAGTGGGGGCCCAGCTTCGCACCATTGAGCCTCACTCCTTCCAAGGGCTCCGCTT
CCTACGCGTGCTCAATGTGTCTCAGAACCTGCTGGAAACTTTGGAAGAGAATGTCTTCTCCTCCCCTA
GGGCTCTGGAGGTCTTGAGCATTAACAACAACCCTCTGGCCTGTGACTGCCGCCTTCTCTGGATCTTG
CAGCGACAGCCCACCCTGCAGTTTGGTGGCCAGCAACCTATGTGTGCTGGCCCAGACACCATCCGTGA
GAGGTCTTTCAAGGATTTCCATAGCACTGCCCTTTCTTTTTACTTTACCTGCAAAAAACCCAAAATCC
GTGAAAAGAAGTTGCAGCATCTGCTAGTAGATGAAGGGCAGACAGTCCAGCTAGAATGCAGTGCAGAT
GGAGACCCGCAGCCTGTGATTTCCTGGGTGACACCCCGAAGGCGTTTCATCACCACCAAGTCCAATGG
AAGAGCCACCGTGTTGGGTGATGGCACCTTGGAAATCCGCTTTGCCCAGGATCAAGACAGCGGGATGT
ATGTTTGCATCGCTAGCAATGCTGCTGGGAATGATACCTTCACAGCCTCCTTAACTGTGAAAGGATTC
GCTTCAGATCGTTTTCTTTATGCGAACAGGACCCCTATGTACATGACCGACTCCAATGACACCATTTC
CAATGGCAGCAATGCCAATACTTTTTCCCTGGACCTTAAAACAATACTGGTGTCTACAGCTATGGGCT
GCTTCACATTCCTGGGAGTGGTTTTATTTTGTTTTCTTCTCCTTTTTGTGTGGAGCCGAGGGAAAGGC
AAGCACAAAAACAGCATTGACCTTGAGTATGTGCCCAAAAAAAACCATGGTGCTGTTGTGGAAGGGGA
GGTAGCTGGACCCAGGAGGTTCAACATGAAAATGATT
NOV3h, CG51514-02
Protein Sequence	SEQ ID NO: 34	579 aa	MW at 65157.5kD
CPARCECSAQNKSVSCHRRRLIAIPEGIPIETKILDLSKNRLKSVNPEEFISYPLLEEIDLSDNIIAN
VEPGAFNNLFNLRSLRLKGNRLKLVPLGVFTGLSNLTKLDISENKIVILLDYMFQDLHNLKSLEVGDN
DLVYISHRAFSGLLSLEQLTLEKCNLTAVPTEALSHLRSLISLHLKHLNINNMPVYAFKRLFHLKHLE
IDYWPLLDMMPANSLYGLNLTSLSVTNTNLSTVPFLAFKHLVYLTHLNLSYNPISTIEAGMFSDLIRL
QELHIVGAQLRTIEPHSFQGLRFLRVLNVSQNLLETLEENVFSSPRALEVLSINNNPLACDCRLLWIL
QRQPTLQFGGQQPMCAGPDTIRERSFKDFHSTALSFYFTCKKPKIREKKLQHLLVDEGQTVQLECSAD
GDPQPVISWVTPRRRFITTKSNGRATVLGDGTLEIRFAQDQDSGMYVCIASNAAGNDTFTASLTVKGF
ASDRFLYANRTPMYMTDSNDTISNGSNANTFSLDLKTILVSTAMGCFTFLGVVLFCFLLLFVWSRGKG
KHKNSIDLEYVPKKNHGAVVEGEVAGPRRFNMKMI

[0390] The NOV3i CG51514-04 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 31.

TABLE 3I
NOV3i, GG51514-04	SEQ ID NO: 35	1536 bp
DNA Sequence	ORF Start: at 1	ORF Stop: end of sequence
TGCCCCGCTCGCTGTGAGTGCTCTGCCCAGAACAAATCTGTTAGCTGTCACAGAAGGCGATTGATCGC
CATCCCAGAGGGCATTCCCATCGAAACCAAAATCTTGGACCTCAGTAAAAACAGGCTAAAAAGCGTCA
ACCCTGAAGAATTCATATCATATCCTCTGCTGGAAGAGATAGACTTGAGTGACAACATCATTGCCAAT
GTGGAACCAGGAGCATTCAACAATCTCTTTAACCTGCGTTCCCTCCGCCTAAAAGGCAATCGTCTAAA
GCTGGTCCCTTTGGGAGTATTCACGGGGCTGTCCAATCTCACTAAGCTTGACATTAGTGAGAATAAGA
TTGTCATTTTACTAGACTACATGTTCCAAGATCTACATAACCTGAAGTCTCTAGAAGTGGGGGACAAT
GATTTGGTTTATATATCACACAGGGCATTCAGTGGGCTTCTTAGCTTGGAGCAGCTCACCCTGGAGAA
ATGCAACTTAACAGCAGTACCAACAGAAGCCCTCTCCCACCTCCGCAGCCTCATCAGCCTGCATCTGA
AGCATCTCAATATCAACAATATGCCTGTGTATGCCTTTAAAAGATTGTTCCACCTGAAACACCTAGAG
ATTGACTATTGGCCTTTACTGGATATGATGCCTGCCAATAGCCTCTACGGTCTCAACCTCACATCCCT
TTCAGTCACCAACACCAATCTGTCTACTGTACCCTTCCTTGCCTTTAAACACCTGGTATACCTGACTC
ACCTTAACCTCTCCTACAATCCCATCAGCACTATTGAAGCAGGCATGTTCTCTGACCTGATCCGCCTT
CAGGAGCTTCATATAGTGGGGGCCCAGCTTCGCACCATTGAGCCTCACTCCTTCCAAGGGCTCCGCTT
CCTACGCGTGCTCAATGTGTCTCAGAACCTGCTGGAAACTTTGGAAGAGAATGTCTTCTCCTCCCCTA
GGGCTCTGGAGGTCTTGAGCATTAACAACAACCCTCTGGCCTGTGACTGCCGCCTTCTCTGGATCTTG
CAGCGACAGCCCACCCTGCAGTTTGGTGGCCAGCAACCTATGTGTGCTGGCCCAGACACCATCCGTGA
GAGGTCCTTCAAGGATTTCCATAGCACTGCCCTTTCTTTTTACTTTACCTGCAAAAAACCCAAAATCC
GTGAAAAGAAGTTGCAGCATCTGCTAGTAGATGAAGGGCAGACAGTCCAGCTAGAATGCAGTGCAGAT
GGAGACCCGCAGCCTGTGATTTCCTGGGTGACACCCCGAAGGCGTTTCATCACCACCAAGTCCAATGG
AAGAGCCACCGTGTTGGGTGATGGCACCTTGGAAATCCGCTTTGCCCAGGATCAAGACAGCGGGATGT
ATGTTTGCATCGCTAGCAATGCTGCTGGGAATGATACCTTCACAGCCTCCTTAACTGTGAAAGGATTC
GCTTCAGATCGTTTTCTTTATGCGAACAGGACCCCTATGTACATGACCGACTCCAATGACACCATTTC
CAATGGCAGCAATGCCAATACTTTTTCCCTGGACCTTAAA
NOV3i, CG51514-04
Protein Sequence	SEQ ID NO: 36	512 aa	MW at 57672.5kD
CPARCECSAQNKSVSCHRRRLIAIPEGIPIETKILDLSKNRLKSVNPEEFISYPLLEEIDLSDNIIAN
VEPGAFNNLFNLRSLRLKGNRLKLVPLGVFTGLSNLTKLDISENKIVILLDYMFQDLHNLKSLEVGDN
DLVYISHRAFSGLLSLEQLTLEKCNLTAVPTEALSHLRSLISLHLKHLNINNMPVYAFKRLFHLKHLE
IDYWPLLDMMPANSLYGLNLTSLSVTNTNLSTVPFLAFKHLVYLTHLNLSYNPISTIEAGMFSDLIRL
QELHIVGAQLRTIEPHSFQGLRFLRVLNVSQNLLETLEENVFSSPRALEVLSINNNPLACDCRLLWIL
QRQPTLQFGGQQPMCAGPDTIRERSFKDFHSTALSFYFTCKKPKIREKKLQHLLVDEGQTVQLECSAD
GDPQPVISWVTPRRRFITTKSNGRATVLGDGTLEIRFAQDQDSGMYVCIASNAAGNDTFTASLTVKGF
ASDRFLYANRTPMYMTDSNDTISNGSNANTFSLDLK

[0391] Further analysis of the NOV3a protein yielded the following properties shown in Table 3J.

TABLE 3J
Protein Sequence Properties NOV3
SignalP analysis:	Cleavage site between residues 28 and 29
PSORT II analysis:
PSG:	a new signal peptide prediction method
	N-region: length 0; pos.chg 0; neg.chg 0
	H-region: length 30; peak value 11.83
	PSG score: 7.43
GvH:	von Heijne's method for signal seq. recognition
	GvH score (threshold: −2.1): 0.70
	possible cleavage site: between 27 and 28
>>> Seems to have a cleavable signal peptide (1 to 27)
ALOM:	Klein et al's method for TM region allocation
	Init position for calculation: 28
	Tentative number of TMS(s) for the threshold 0.5:  1
	Number of TMS(s) for threshold 0.5: 1
	INTEGRAL  Likelihood = −11.99 Transmembrane 549-565
	PERIPHERAL Likelihood = 5.04 (at 264)
	ALOM score: −11.99 (number of TMSs: 1)
MTOP:	Prediction of membrane topology (Hartmann et al.)
	Center position for calculation: 13
	Charge difference: 1.0 C( 2.5) − N( 1.5)
	C > N: C-terminal side will be inside
>>>Caution: Inconsistent mtop result with signal peptide
>>> membrane topology: type 1a (cytoplasmic tail 566 to 606)
MITDISC: discrimination of mitochondrial targeting seq
	R content:	1	Hyd Moment(75):	4.08
	Hyd Moment(95):	4.23	G content:	3
	D/E content:	1	S/T content:	4
	Score: −4.81
Gavel: prediction of cleavage sites for mitochondrial preseq
	R-2 motif at 57 RRL|IA
NUCDISC: discrimination of nuclear localization signals
	pat4: HRRR (3) at 44
	pat4: KKPK (4) at 408
	pat4: PRRR (4) at 447
	pat7: FKIREKK (3) at 410
	pat7: PRRRFIT (5) at 447
	bipartite: none
	content of basic residues:  9.9%
	NLS Score: 0.91
KDEL: ER retention motif in the C-terminus: none
ER Membrane Retention Signals:
	KKXX-like motif in the C-terminus: NMKM
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: 580
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
11.1%: plasma membrane
11.1%: vesicles of secretory system
11.1%: extracellular, including cell wall
>> prediction for CG51514-01 is end (k = 9)

[0392] PFam analysis predicts that the NOV3a protein contains the domains shown in the Table 3K.

TABLE 3K
Domain Analysis of NOV3
	NOV3a	Identities/
	Match	Similarities
Pfam Domain	Region	for the Matched Region	Expect Value
LRRNT	27 . . . 56	13/35 (37%)	1.8e−05
		23/35 (66%)
LRR	106 . . . 129	12/25 (48%)	0.51
		20/25 (80%)
LRR	178 . . . 201	10/25 (40%)	0.65
		19/25 (76%)
LRR	250 . . . 273	9/25 (36%)	0.6
		21/25 (84%)
LRR	274 . . . 297	8/25 (32%)	0.063
		21/25 (84%)
LRR	298 . . . 321	9/25 (36%)	0.26
		22/25 (88%)
LRR	322 . . . 345	9/25 (36%)	0.64
		20/25 (80%)
LRRCT	355 . . . 408	15/58 (26%)	0.0012
		40/58 (69%)
ig	425 . . . 485	16/64 (25%)	3.1e−06
		41/64 (64%)

Example 4. NOV4, CG52053

[0393] The NOV4a CG52053-01 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 4A.

TABLE 4A
NOV4a Sequence Analysis
NOV4a, CG52053-01	SEQ ID NO: 37	1587 bp
DNA Sequence	ORF Start: ATG at 540	ORF Stop: end of sequence
AGAGGCTCTCAAATTAGATCAAGAAATGCCTTTAACAGAAGTGAAGAGTGAACCTGCTCCTGACATGG
CGGCTTCACTCTCAGGAGAATACACGGATACAGCTAGTGTTTGACAATCAGTTTGGATTAGAGGAAGC
AGAAAATGATATCTGTAGGTATGATTTTGTGGAAGTTGAAGATATATCCGAAACCAGTACCATTATTA
GAGGACGATGGTGTGGACACAAGGAAGTTCCTCCAAGGATAAAATCAAGAACGAACCAAATTAAAATC
ACATTCAAGTCCGATGACTACTTTGTGGCTAAACCTGGATTCAAGATTTATTATTCTTTGCTGGAAGA
TTTCCAACCCGCAGCAGCTTCAGAGACCAACTGGGAATCTGTCACAAGCTCTATTTCAGGGGTATCCT
ATAACTCTCCATCAGTAACGGATCCCACTCTGATTGCGGATGCTCTGGACAAAAAAATTGCAGAATTT
GATACAGTGGAAGATCTGCTCAAGTACTTCAATCCAGAGTCATGGCAAGAAGATCTTGAGAATATGTA
TCTGGACACCCCTCGGTATCGAGGCAGGTCATACCATGACCGGAAGTCAAAAGTTGACCTGGATAGGC
TCAATGATGATGCCAAGCGTTACAGTTGCACTCCCAGGAATTACTCGGTCAATATAAGAGAAGAGCTG
AAGTTGGCCAATGTGGTCTTCTTTCCACGTTGCCTCCTCGTGCAGCGCTGTGGAGGAAATTGTGGCTG
TGGAACTGTCAACTGGAGGTCCTGCACATCCAATTCAGGGAAAACCGTGAAAAAGTATCATGAGGTAT
TACAGTTTGAGCCTGGCCACATCAAGAGGAGGGGTAGAGCTAAGACCATGGCTCTAGTTGACATCCAG
TTGGATCACCATGAACGATGTGATTGTATCTGCAGCTCAAGACCACCTCGATAAGAGAATGTCCACAT
CCTTACATTAAGCCTGAAAGAACCTTTAGTTTAAGGAGGGTGAGATAAGAGACCCTTTTCCTACCAGC
AACCAAACTTACTACTAGCCTGCAATGCAATGAACACAAGTGGTTGCTGAGTCTCAGCCTTGCTTTGT
TAATGCCATGGCAAGTAGAAAGGTATATCATCAACTTCTATACCTAAGAATATAGGATTGCATTTAAT
AATAGTGTTTGAGGTTATATATGCACAAACACACACAGAAATATATTCATGTCTATGTGTATATAGAT
CAAATGTTTTTTTTGGTATATATAACCAGGTACACCAGAGCTTACATATGTTTGAGTTAGACTCTTAA
AATCCTTTGCCAAAATAAGGGATGGTCAAATATATGAAACATGTCTTTAGAAAATTTAGGAGATAAAT
TTATTTTTAAATTTTGAAACACAAACAATTTTGAATCTTGCTCTCTTAAAGAAAAGCATCTTGTATAT
TAAAAATCAAAAGATGAGGCTTTCTTACATATACATCTTAGTTGATTATTAAAAAAGGAAAAATATGG
TTTCCAGAGAAAAGGCCAATACCTAAGCATTTTTTCCATGAGAAGCACTGCATACTTACCTATGTGGA
CTATAATAACCTGTCTCCAAAAC
NOV4a, CG52053-01
Protein Sequence	SEQ ID NO: 38	132 aa	MW at 15380.5kD
MYLDTPRYRGRSYHDRKSKVDLDRLNDDAKRYSCTPRNYSVNIREELKLANVVFFPRCLLVQRCGGNC
GCGTVNWRSCTCNSGKTVKKYHEVLQFEPGHIKRRGRAKTMALVDIQLDHHERCDCICSSRPPR

[0394] The NOV4b CG52053-03, NOV4c CG52053-04, NOV4d CG52053-05, NOV4e CG52053-06, NOV4f CG52053-07 clones were analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 4B.

TABLE 4B
NOV4b, CG52053-03	SEQ ID NO: 39	3200 bp
DNA Sequence	ORF Start: ATG at 247	ORF Stop: end of sequence
GAGGCAACCTGTTGTTTGCCCAGCTCCTATTGATCAAGTCAGAGCTACAAGGAAATGCGGCACACACA
CGCGCTTGGAAAGTTTAGCTTACAGGAAGTTTTCGGAGAGCAGCGCCAGTAACTGGGCGGCCGGGACA
ACACAGGCGGTGAAGGCGAGGGACTGTGCAGTAGAAATCCGCCGACTCAACCCTTTGGGCTTTATTTA
TTTACTTTTGGAGCAACGCGATCCCTAGGTCGCTGAGCCCAAATGCAACGGCTCGTTTTAGTCTCCAT
TCTCCTGTGCGCGAACTTTAGCTGCTATCCGGACACTTTTGCGACTCCGCAGAGAGCATCCATCAAAG
CTTTGCGCAATGCCAACCTCAGGAGAGATGAGAGCAATCACCTCACAGACTTGTACCAGAGAGAGGAG
AACATTCAGGTGACAAGCAATGGCCATGTGCAGAGTCCTCGCTTCCCGAACAGCTACCCAAGGAACCT
GCTTCTGACATGGTGGCTCCGTTCCCAGGAGAAAACACGGATACAACTGTCCTTTGACCATCAATTCG
GACTAGAGGAAGCAGAAAATGACATTTGTAGGTATGACTTTGTGGAAGTTGAAGAAGTCTCAGAGAGC
AGCACTGTTGTCAGAGGAAGATGGTGTGGCCACAAGGAGATCCCTCCAAGGATAACGTCAAGAACAAA
CCAGATTAAAATCACATTTAAGTCTGATGACTACTTTGTGGCAAAACCTGGATTCAAGATTTATTATT
CATTTGTGGAAGATTTCCAACCGGAAGCAGCCTCAGAGACCAACTGGGAATCAGTCACAAGCTCTTTC
TCTGGGGTGTCCTATCACTCTCCATCAATAACGGACCCCACTCTCACTGCTGATGCCCTGGACAAAAC
TGTCGCAGAATTCGATACCGTGGAAGATCTACTTAAGCACTTCAATCCAGTGTCTTGGCAAGATGATC
TGGAGAATTTGTATCTGGACACCCCTCATTATAGAGGCAGGTCATACCATGATCGGAAGTCCAAAGTG
GACCTGGACAGGCTCAATGATGATGTCAAGCGTTACAGTTGCACTCCCAGGAATCACTCTGTGAACCT
CAGGGAGGAGCTGAAGCTGACCAATGCAGTCTTCTTCCCACGATGCCTCCTCGTGCAGCGCTGTGGTG
GCAACTGTGGTTGCGGAACTGTCAACTGGAAGTCCTGCACATGCAGCTCAGGGAAGACAGTGAAGAAG
TATCATGAGGTATTGAAGTTTGAGCCTGGACATTTCAAGAGAAGGGGCAAAGCTAAGAATATGGCTCT
TGTTGATATCCAGCTGGATCATCATGAGCGATGTGACTGTATCTGCAGCTCAAGACCACCTCGATAAA
ACACTATGCACATCTGTACTTTGATTATGAAAGGACCTTTAGGTTACAAAAACCCTAAGAAGCTTCTA
ATCTCAGTGCAATGAATGCATATGGAAATGTTGCCTTGTTAGTGCCATGGCAAGAAGAAGCAAATATC
ATTAATTTCTATATACATAAACATAGGAATTCACTTATCAATAGTATGTGAAGATATGTATATATACT
TATATACATGACTAGCTCTATGTATGTAAATAGATTAAATACTTTATTCAGTATATTTACTGAAGTCC
CCTAGAGGCAAATGATATTACTTGATATTTTGCTAAAATAAGGGAATGTGTCAAGCATATAAAATATC
TTTCAAAAATTCAAAAGGTAAGTTTATTCTAAAGCTTTGTATGACAAAATATATCAGATTTTGCTCAC
TTAAAGAAGGCACTTGTCCATTAAATGAAAGATGAGACTTTCTTCTGTGAATAAATCTAATTATGTGA
AGACAAATACATAGTTTCTGGCAATAAAAACAAGTTTTGAAATATTTTCTTCATGAGATGTACTACTC
ACCTACCAATGTGGACAGTTATTATCTGTCTCCACAACTATGCCAAAGTAATACAGGATATTTAACAA
TCAAGTCAATCAAGTCATTAAGTCCTCTTCCATGTATTTTCTCAATGCAAGCTAAGTAACTGAGCACC
CTTCTCAATGAATTGCTCAGGGACTTGTGGTGATAATTGGCAAGAGATATTCAATAGGCAAGCAATAG
GTTGCTGTAGAATTTTTGAATTTTTTTTTTTATTTTAAAGTCTGCAGAAAAGCAAGTGTTTTCAGGAA
GAACATGATATTTATTACACATGAGCCTTTAAATATGGTAGTCATGGCAAGACTTGGGTGATAGAAAG
TCAGAAATAAGCAAATGTTGACATAACTGGAAATCAAATGGGCTGTTTGATAAGGTCTACATTTAAAA
GTGGGTCAAAATCTTCTAAACTGTGCCAATAATTTTTCTGTGTTTTGCTCTTGCATTTCTATCTTTTC
AATATATACACATAAACTTATATTGTGCTATATGAGACAAGCTATCATGGAATATTTATAGCCTAAAA
TATTTATGTATTAACAAAACAACTAGAGCCAGCTAAGTTGTGGAGGCACAGATTTGGTCCTGCTGTTC
CACTGGAAAGCTTTTTGTTCTGATTTTTAGGAGTGAGTTAAGTTTCCCCAGTGGTGCCTCTATATCTT
TTCTAAAGAGATTGAGTCCAGAAACAGGAAGTTGCTCATTGTTCTCCAAACAAAATGTTTAGGAGGGA
ATCCTGAAGTCAAGTTAACTTGGTTCTGCTACTAGGAAACTATATTTTTCTTCCTGCCTTTAGAGTAG
AAAAGAAAACTGATTTATTCGGTGAGTCTAACACTACCCTGAGCACAAAGTGTTTTTTTTTTCTGAAT
CTGTGCACACGGCCCTTTGGTCTGGTGTCAGATGAATAGCTTATACACACTTACATTGCTAAGGATGA
TGCTGTCTAAGCCAAGTTATCAGCTGTGTGCTCAACAAATCTATGCTTACTGACACATATATTCTAAA
GGTTCTATGCAGTCAATTACCTGCCAGTTCTACTTAAATGATTATTAAAATTAAATAGTATATTGTTG
TCAAGCATGCCACAGAACAATAAGAAGTAAGCCAGGCCCAATTTGCAAGCTTCCTGTGAAACAATGGC
TCCTATAAAAAACACCAAAATGTACATTATCTTACTCACTTGTAAAGGGCACAGATCAATCATAACTG
TACATATGAAATGTTAGAGGGTTTTTTCAATAAACCTTCTAGGTGGTGATAACCAAAAAAAAAAAAAA
AAAA
NOV4b, CG52053-03
Protein Sequence	SEQ ID NO: 40	370 aa	MW at 42808.6kD
MQRLVLVSILLCANFSCYPDTFATPQRASIKALRNANLRRDESNHLTDLYQREENIQVTSNGHVQSPR
FPNSYPRNLLLTWWLRSQEKTRIQLSFDHQFGLEEAENDICRYDFVEVEEVSESSTVVRGRWCGHKEI
PPRITSRTNQIKITFKSDDYFVAKPGFKIYYSFVEDFQPEAASETNWESVTSSFSGVSYHSPSITDPT
LTADALDKTVAEFDTVEDLLKHFNPVSWQDDLENLYLDTPHYRGRSYHDRKSKVDLDRLNDDVKRYSC
TPRNHSVNLREELKLTNAVFFPRCLLVQRCGGNCGCGTVNWKSCTCSSGKTVKKYHEVLKFEPGHFKR
RGKAKNMALVDIQLDHHERCDCICSSRPPR
NOV4c, CG52053-04	SEQ ID NO: 41	369 bp
DNA Sequence	ORF Start: at 1	ORF Stop: at 370
GGCAGGTCATACCATGACCGGAAGTCAAAAGTTGACCTGGATAGGCTCAATGATGATGCCAAGCGTTA
CAGTTGCACTCCCAGGAATTACTCGGTCAATATAAGAGAAGAGCTGAAGTTGGCCAATGTGGTCTTCT
TTCCACGTTGCCTCCTCGTGCAGCGCTGTGGAGGAAATTGTGGCTGTGGAACTGTCAACTGGAGGTCC
TGCACATGCAATTCAGGGAAAACCGTGAAAAAGTATCATGAGGTATTACAGTTTGAGCCTGGCCACAT
CAAGAGGAGGGGTAGAGCTAAGACCATGGCTCTAGTTGACATCCAGTTGGATCACCATGAACGATGTG
ATTGTATCTGCAGCTCAAGACCACCTCGA
NOV4c, CG52053-04
Protein Sequence	SEQ ID NO: 42	123 aa	MW at 14184.1kD
GRSYHDRKSKVDLDRLNDDAKRYSCTPRNYSVNIREELKLANVVFFPRCLLVQRCGGNCGCGTVNWRS
CTCNSGKTVKKYHEVLQFEPGHIKRRGRAKTMALVDIQLDHHERCDCICSSRPPR
NOV4d, CG52053-05	SEQ ID NO: 43	1267 bp
DNA Sequence	ORF Start: ATG at 173	ORF Stop: end of sequence
ATGTTCTCTACAACACCAAGGCTCATTAAAATATTTTAAATATTAATATACATTTCTTCTGTCAGAAA
TACATAAAACTTTATTATATCAGCGCAGGGCGGCGCGGCGTCGGTCCCGGGAGCAGAACCCGGCTTTT
TCTTGGAGCGACGCTGTCTCTAGTCGCTGATCCCAAATGCACCGGCTCATCTTTGTCTACACTCTAAT
CTGCGCAAACTTTTGCAGCTGTCGGGACACTTCTGCAACCCCGCAGAGCGCATCCATCAAAGCTTTGC
GCAACGCCAACCTCAGGCGAGATGACTTGTACCGAAGAGATGAGACCATCCAGGTGAAAGGAAACGGC
TACGTGCAGAGTCCTAGATTCCCGAACAGCTACCCCAGGAACCTGCTCCTGACATGGCGGCTTCACTC
TCAGGAGAATACACGGATACAGCTAGTGTTTGACAATCAGTTTGGATTAGAGGAAGCAGAAAATGATA
TCTGTAGGTATGATTTTGTGGAAGTTGAAGATATATCCGAAACCAGTACCATTATTAGAGGACGATGG
TGTGGACACAAGGAAGTTCCTCCAAGGATAAAATCAAGAACGAACCAAATTAAAATCACATTCAAGTC
CGATGACTACTTTGTGGCTAAACCTGGATTCAAGATTTATTATTCTTTGCTGGAAGATTTCCAACCCG
CAGCAGCTTCAGAGACCAACTGGGAATCTGTCACAAGCTCTATTTCAGGGGTATCCTATAACTCTCCA
TCAGTAACGGATCCCACTCTGATTGCGGATGCTCTGGACAAAAAAATTGCAGAATTTGATACAGTGGA
AGATCTGCTCAAGTACTTCAATCCAGAGTCATGGCAAGAAGATCTTGAGAATATGTATCTGGACACCC
CTCGGTATCGAGGCAGGTCATACCATGACCGGAAGTCAAAAGTTGACCTGGATAGGCTCAATGATGAT
GCCAAGCGTTACAGTTGCACTCCCAGGAATTACTCGGTCAATATAAGAGAAGAGCTGAAGTTGGCCAA
TGTGGTCTTCTTTCCACGTTGCCTCCTCGTGCAGCGCTGTGGAGGAAATTGTGGCTGTGGAACTGTCA
ACTGGAGGTCCTGCACATGCAATTCAGGGAAAACCGTGAAAAAGTATCATGAGGTATTACAGTTTGAG
CCTGGCCACATCAAGAGGAGGGGTAGAGCTAAGACCATGGCTCTAGTTGACATCCAGTTGGATCACCA
TGAACGATGTGATTGTATCTGCAGCTCAAGACCACCTCGATAA
NOV4d, CG52053-05
Protein Sequence	SEQ ID NO: 44	364 aa	MW at 42166.1kD
MHRLIFVYTLICANFCSCRDTSATPQSASIKALRNANLRRDDLYRRDETIQVKGNGYVQSPRFPNSYP
RNLLLTWRLHSQENTRIQLVFDNQFGLEEAENDICRYDFVEVEDISETSTIIRGRWCGHKEVPPRIKS
RTNQIKITFKSDDYFVAKPGFKIYYSLLEDFQPAAASETNWESVTSSISGVSYNSPSVTDPTLIADAL
DKKIAEFDTVEDLLKYFNPESWQEDLENMYLDTPRYRGRSYHDRKSKVDLDRLNDDAKRYSCTPRNYS
VNIREELKLANVVFFPRCLLVQRCGGNCGCGTVNWRSCTCNSGKTVKKYHEVLQFEPGHIKRRGRAKT
MALVDIQLDHHERCDCICSSRPPR
NOV4e, CG52053-06	SEQ ID NO: 45	1041 bp
DNA Sequence	ORF Start: at 1	ORF Stop: end of sequence
ACCCCGCAGAGCGCATCCATCAAAGCTTTGCGCAACGCCAACCTCAGGCGAGATGAGAGCAATCACCT
TCCCGAACAGCTACCCCAGGAACCTGCTCCTGACATGGCGGCTTCACTCTCAGGAGAATACACGGATA
GGAAGTTGAAGATATATCCGAAACCAGTACCATTATTAGAGGACGATGGTGTGGACACAAGGAAGTTC
CTCCAAGGATAAAATCAAGAACGAACCAAATTAAAATCACATTCAAGTCCGATGACTACTTTGTGGCT
AAACCTGGATTCAAGATTTATTATTCTTTGCTGGAAGATTTCCAACCCGCAGCAGCTTCAGAGACCAA
CTGGGAATCTGTCACAAGCTCTATTTCAGGGGTATCCTATAACTCTCCATCAGTAACGGATCCCACTC
TGATTGCGGATGCTCTGGACAAAAAAATTGCAGAATTTGATACAGTGGAAGATCTGCTCAAGTACTTC
AATCCAGAGTCATGGCAAGAAGATCTTGAGAATATGTATCTGGACACCCCTCGGTATCGAGGCAGGTC
ATACCATGACCGGAAGTCAAAAGTTGACCTGGATACGCTCAATGATGATGCCAAGCGTTACAGTTGCA
CTCCCAGGAATTACTCGGTCAATATAAGAGAAGAGCTGAAGTTGGCCAATGTGGTCTTCTTTCCACGT
TGCCTCCTCGTGCAGCGCTGTGGAGGAAATTGTGGCTGTGGAACTGTCAACTGGAGGTCCTGCACATG
CAATTCAGGGAAAACCGTGAAAAAGTATCATGAGGTATTACAGTTTGAGCCTGGCCACATCAAGAGGA
GGGGTAGAGCTAAGACCATGGCTCTAGTTGACATCCAGTTGGATCACCATGAACGATGTGATTGTATC
TGCAGCTCAAGACCACCTCGA
NOV4e, CG52053-06
Protein Sequence	SEQ ID NO: 46	347 aa	MW at 40200.7kD
TPQSASIKALRNANLRRDESNHLTDLYRRDETIQVKGNGYVQSPRFPNSYPRNLLLTWRLHSQENTRI
QLVFDNQFGLEEAENDICRYDFVEVEDISETSTIIRGRWCGHKEVPPRIKSRTNQIKITFKSDDYFVA
KPGFKIYYSLLEDFQPAAASETNWESVTSSISGVSYNSPSVTDPTLIADALDKKIAEFDTVEDLLKYF
NPESWQEDLENMYLDTPRYRGRSYHDRKSKVDLDRLNDDAKRYSCTPRNYSVNIREELKLANVVFFPR
CLLVQRCGGNCGCGTVNWRSCTCNSGKTVKKYHEVLQFEPGHIKRRGRAKTMALVDIQLDHHERCDCI
CSSRPPR
NOV4f, CG52053-07	SEQ ID NO: 47	1041 bp
DNA Sequence	ORF Start: at 1	ORF Stop: end of sequence
ACTCCGCAGAGAGCATCCATCAAAGCTTTGCGCAATGCCAACCTCAGGAGAGATGAGAGCAATCACCT
CACAGACTTGTACCAGAGAGAGGAGAACATTCAGGTGACAAGCAATGGCCATGTGCAGAGTCCTCGCT
TCCCGAACAGCTACCCAAGGAACCTGCTTCTGACATGGTCGCTCCGTTCCCAGGAGAAAACACGGATA
CAACTGTCCTTTGACCATCAATTCGGACTAGAGGAAGCAGAAAATGACATTTGTAGGTATGACTTTGT
GGAAGTTGAAGAAGTCTCAGAGAGCAGCACTGTTGTCAGAGGAAGATGGTGTGGCCACAAGGAGATCC
CTCCAAGGATAATGTCAAGAACAAACCAGATTAAAATCACATTTAAGTCTGATGACTACTTTGTGGCA
AAACCTGGATTCAAGATTTATTATTCATTTGTGGAAGATTTCCAACCGGAAGCAGCCTCAGAGACCAA
CTGGGAATCAGTCACAAGCTCTTTCTCTGGGGTGTCCTATCACTCTCCATCAATAACGGACCCCACTC
TCACTGCTCATGCCCTGGACAAAACTGTCGCAGAATTCGATACCGTGGAAGATCTACTTAAGCACTTC
AATCCAGTGTCTTGCCAAGATGATCTGGAGAATTTGTATCTGGACACCCCTCATTATAGAGGCAGGTC
ATACCATGATCGGAAGTCCAAAGTGGACCTGGACAGGCTCAATGATGATGTCAAGCGTTACAGTTGCA
CTCCCAGGAATCACTCTGTGAACCTCAGGCAGGAGCTGAAGCTGACCAATGCAGTCTTCTTCCCACGA
TGCCTCCTCGTGCAGCGCTGTGGTGGCAACTGTGGTTGCGGAACTGTCAACTGGAAGTCCTGCACATG
CAGCTCAGGGAAGACAGTGAAGAAGTATCATGAGGTATTGAAGTTTGAGCCTGGACATTTCAAGAGAA
GGGGCAAAGCTAAGAATATGGCTCTTGTTGATATCCAGCTGGATCATCATGAGCGATGTGACTGTATC
TGCAGCTCAAGACCACCTCGA
NOV4f, CG52053-07
Protein Sequence	SEQ ID NO: 48	347 aa	MW at 40251.7kD
TPQRASIKALRNANLRRDESNHLTDLYQREENIQVTSNGHVQSPRFPNSYPRNLLLTWWLRSQEKTRI
QLSFDHQFGLEEAENDICRYDFVEVEEVSESSTVVRGRWCGHKEIPPRIMSRTNQIKITFKSDDYFVA
KPGFKIYYSFVEDFQPEAASETNWESVTSSFSGVSYHSPSITDPTLTADALDKTVAEFDTVEDLLKHF
NPVSWQDDLENLYLDTPHYRGRSYHDRKSKVDLDRLNDDVKRYSCTPRNHSVNLREELKLTNAVFFPR
CLLVQRCGGNCGCGTVNWKSCTCSSGKTVKKYHEVLKFEPGHFKRRGKAKNMALVDIQLDHHERCDCI
CSSRPPR

[0395] The NOV4g 13376547 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 4C.

TABLE 4C
NOV4g Sequence Analysis
NOV4g, 13376547	SEQ ID NO: 49	1587 bp
DNA Sequence	ORF Start: ATG at 540	ORF Stop: end of sequence
AGAGGCTCTCAAATTAGATCAAGAAATGCCTTTAACAGAAGTGAAGAGTGAACCTGCTCCTGACATGG
CGGCTTCACTCTCAGGAGAATACACGGATACAGCTAGTGTTTGACAATCAGTTTGGATTAGAGGAAGC
AGAAAATCATATCTGTAGGTATGATTTTGTGGAAGTTGAAGATATATCCGAAACCAGTACCATTATTA
GAGGACGATGGTGTGGACACAAGGAAGTTCCTCCAAGGATAAAATCAAGAACGAACCAAATTAAAATC
ACATTCAAGTCCGATGACTACTTTGTGGCTAAACCTGGATTCAAGATTTATTATTCTTTGCTGGAAGA
TTTCCAACCCGCAGCAGCTTCAGAGACCAACTGGGAATCTGTCACAAGCTCTATTTCAGGGGTATCCT
ATAACTCTCCATCAGTAACGGATCCCACTCTGATTGCGGATGCTCTGGACAAAAAAATTGCAGAATTT
GATACAGTGGAAGATCTGCTCAAGTACTTCAATCCAGAGTCATGGCAAGAAGATCTTGAGAATATGTA
TCTGGACACCCCTCGGTATCCAGGCAGGTCATACCATGACCGGAAGTCAAAAGTTGACCTGGATAGGC
TCAATGATGATGCCAAGCGTTACAGTTGCGCTCCCAGGAATTACTCGGTCAATATAAGAGAAGAGCTG
AAGTTGGCCAATGTGGTCTTCTTTCCACGTTGCCTCCTCGTGCAGCGCTGTGGAGGAAATTGTGGCTG
TGGAACTGTCAACTGGAGGTCCTGCACATGCAATTCAGGGAAAACCGTGAAAAAGTATCATGAGGTAT
TACAGTTTGAGCCTGGCCACATCAAGAGGAGGGGTAGAGCTAAGACCATGGCTCTAGTTGACATCCAG
TTGGATCACCATGAACGATGTGATTGTATCTGCAGCTCAAGACCACCTCGATAAGAGAATGTGCACAT
CCTTACATTAAGCCTGAAAGAACCTTTAGTTTAAGGAGGGTGAGATAAGAGACCCTTTTCCTACCAGC
AACCAAACTTACTACTAGCCTGCAATGCAATGAACACAAGTGGTTGCTGAGTCTCAGCCTTGCTTTGT
TAATGCCATGGCAAGTAGAAAGGTATATCATCAACTTCTATACCTAAGAATATAGGATTGCATTTAAT
AATAGTGTTTGAGGTTATATATGCACAAACACACACAGAAATATATTCATGTCTATGTGTATATAGAT
CAAATGTTTTTTTTGGTATATATAACCAGGTACACCAGAGCTTACATATGTTTGAGTTAGACTCTTAA
AATCCTTTGCCAAAATAAGGGATGGTCAAATATATGAAACATGTCTTTAGAAAATTTAGGAGATAAAT
TTATTTTTAAATTTTGAAACACAAAACAATTTTGAATCTTGCTCTCTTAAAGAAAGCATCTTGTATAT
TAAAAATCAAAAGATGAGGCTTTCTTACATATACATCTTAGTTGATTATTAAAAAAGGAAAAATATGG
TTTCCAGAGAAAAGGCCAATACCTAAGCATTTTTTCCATGAGAAGCACTGCATACTTACCTATGTGGA
CTATAATAACCTGTCTCCAAAAC
NOV4g, 13376547
Protein Sequence	SEQ ID NO: 50	132 aa	MW at 15380.5kD
MYLDTPRYRGRSYHDRKSKVDLDRLNDDAKRYSCARNYSVNIREELKLANVVFFPRCLLVQRCGGNC
GCGTVNWRSCTCNSGKTVKKYHEVLQFEPGHIKRRGRAKTMALVDIQLDHHERCDCICSSRPPR

[0396] The NOV4h 13376546 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 4D.

TABLE 4D
NOV4h Sequence Analysis
NOV4h, 13376546	SEQ ID NO: 51	1587 bp
DNA Sequence	ORF Start: ATG at 540	ORF Stop: end of sequence
AGAGGCTCTCAAATTAGATCAAGAAATGCCTTTAACAGAAGTGAAGAGTGAACCTGCTCCTGACATGG
CGGCTTCACTCTCAGGAGAATACACGGATACAGCTAGTGTTTGACAATCAGTTTGGATTAGAGGAAGC
AGAAAATGATATCTGTAGGTATGATTTTGTGGAAGTTGAAGATATATCCGAAACCAGTACCATTATTA
GAGGACGATGGTGTGGACACAAGGAAGTTCCTCCAAGGATAAAATCAAGAACGAACCAAATTAAAATC
ACATTCAAGTCCGATGACTACTTTGTCGCTAAACCTGGATTCAAGATTTATTATTCTTTGCTGGAAGA
TTTCCAACCCGCAGCAGCTTCAGAGACCAACTGGGAATCTGTCACAAGCTCTATTTCAGGGGTATCCT
ATAACTCTCCATCAGTAACGGATCCCACTCTGATTGCGGATGCTCTGGACAAAAAAATTGCAGAATTT
GATACAGTGGAAGATCTGCTCAAGTACTTCAATCCAGAGTCATGGCAAGAAGATCTTGAGAATATGTA
TCTGGACACCCCTCGGTATCGAGGCAGGTCATACCATGACCGGAAGTCAAAAGTTGACCTGGATAGGC
TCAATGATGATGCCAAGCGTTACAGTTGCACTCCCAGGAATTACTCGGTCAATATAAGAGAAGAGCTG
AAGTTGGCCAATGCGGTCTTCTTTCCACGTTGCCTCCTCGTGCAGCGCTGTGGAGGAAATTGTGGCTG
TGGAACTGTCAACTGGAGGTCCTGCACATGCAATTCAGGGAAAACCGTGAAAAAGTATCATGAGGTAT
TACAGTTTGAGCCTGGCCACATCAAGAGGAGGGGTAGAGCTAAGACCATGGCTCTAGTTGACATCCAG
TTGGATCACCATGAACGATGTGATTGTATCTGCAGCTCAAGACCACCTCGATAAGAGAATGTGCACAT
CCTTACATTAAGCCTGAAAGAACCTTTAGTTTAAGGAGGGTGAGATAAGAGACCCTTTTCCTACCAGC
AACCAAACTTACTACTAGCCTGCAATGCAATGAACACAAGTGGTTGCTGAGTCTCAGCCTTGCTTTGT
TAATGCCATGGCAAGTAGAAAGGTATATCATCAACTTCTATACCTAAGAATATAGGATTGCATTTAAT
AATAGTGTTTGAGGTTATATATGCACAAACACACACAGAAATATATTCATGTCTATGTGTATATAGAT
CAAATGTTTTTTTTGGTATATATAACCAGGTACACCAGAGCTTACATATGTTTGAGTTAGACTCTTAA
AATCCTTTGCCAAAATAAGGGATGGTCAAATATATGAAACATGTCTTTAGAAAATTTAGGAGATAAAT
TTATTTTTAAATTTTGAAACACAAAACAATTTTGAATCTTGCTCTCTTAAAGAAAGCATCTTGTATAT
TAAAAATCAAAAGATGAGGCTTTCTTACATATACATCTTAGTTGATTATTAAAAAAGGAAAAATATGG
TTTCCAGAGAAAAGGCCAATACCTAAGCATTTTTTCCATGAGAAGCACTGCATACTTACCTATGTGGA
CTATAATAACCTGTCTCCAAAAC
NOV4h, 13376546
Protein Sequence	SEQ ID NO: 52	132 aa	MW at 15380.5kD
MYLDTPRYRGRSYHDRKSKVDLDRLNDDAKRYSCTPRNYSVNIREELKLANAVFFPRCLLVQRCGGNC
GCGTVNWRSCTCNSGKTVKKYHEVLQFEPGHIKRRGRAKTMALVDIQLDHHERCDCICSSRPPR

[0397] The NOV4i 13376545 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 4E.

TABLE 4E
NOV4i Sequence Analysis
NOV4i, 13376545	SEQ ID NO: 53	1587 bp
DNA Sequence	ORF Start: ATG at 540	ORF Stop: end of sequence
AGAGGCTCTCAAATTAGATCAAGAAATGCCTTTAACAGAAGTGAAGAGTGAACCTGCTCCTGACATGG
CGGCTTCACTCTCAGGAGAATACACGGATACAGCTAGTGTTTGACAATCAGTTTGGATTAGAGGAAGC
AGAAAATGATATCTGTAGGTATGATTTTGTGGAAGTTGAAGATATATCCGAAACCAGTACCATTATTA
GAGGACGATGGTGTGGACACAAGGAAGTTCCTCCAAGGATAAAATCAAGAACGAACCAAATTAAAATC
ACATTCAAGTCCGATGACTACTTTGTGGCTAAACCTGGATTCAAGATTTATTATTCTTTGCTGGAAGA
TTTCCAACCCGCAGCAGCTTCAGAGACCAACTGGGAATCTGTCACAAGCTCTATTTCACGGGTATCCT
ATAACTCTCCATCAGTAACGGATCCCACTCTGATTGCGGATGCTCTGGACAAAAAAATTGCAGAATTT
GATACAGTGGAAGATCTGCTCAAGTACTTCAATCCAGAGTCATGGCAAGAAGATCTTGAGAATATGTA
TCTGGACACCCCTCGGTATCGAGGCAGGTCATACCATGACCGGAAGTCAAAAGTTGACCTGGATAGGC
TCAATGATGATGCCAAGCGTTACAGTTGCACTCCCAGGAATTACTCGGTCAATATAAGAGAAGAGCTG
AAGTTGGCCAATGTGGTCTTCTTTCCACGTTACTCCTCGTGCAGCGCTGTGGAGGAAATTGTGGCTG
TGGAACTGTCAACTGGAGGTCCTGCACATGCAATTCAGGGAAAACCGTGAAAAAGTATCATGAGGTAT
TACAGTTTGAGCCTGGCCACATCAAGAGGAGGGGTAGAGCTAAGACCATGGCTCTAGTTGACATCCAG
TTGGATCACCATGAACGATGTGATTGTATCTGCAGCTCAAGACCACCTCGATAAGAGAATGTGCACAT
CCTTACATTAACCCTGAAAGAACCTTTAGTTTAACGAGGGTGAGATAAGAGACCCTTTTCCTACCAGC
AACCAAACTTACTACTAGCCTGCAATGCAATCAACACAAGTGGTTGCTGAGTCTCAGCCTTGCTTTGT
TAATGCCATGGCAAGTAGAAAGGTATATCATCAACTTCTATACCTAAGAATATAGGATTGCATTTAAT
AATAGTGTTTGAGGTTATATATGCACAAACACACACAGAAATATATTCATGTCTATGTGTATATAGAT
CAAATGTTTTTTTTGGTATATATAACCAGGTACACCAGAGCTTACATATGTTTGAGTTAGACTCTTAA
AATCCTTTGCCAAAATAAGGGATGGTCAAATATATGAAACATGTCTTTAGAAAATTTAGGAGATAAAT
TTATTTTTAAATTTTGAAACACAAAACAATTTTGAATCTTGCTCTCTTAAAGAAAGCATCTTGTATAT
TAAAAATCAAAAGATGAGGCTTTCTTACATATACATCTTAGTTGATTATTAAAAAAGGAAAAATATGG
TTTCCAGAGAAAAGGCCAATACCTAAGCATTTTTTCCATGAGAAGCACTGCATACTTACCTATGTGGA
CTATAATAACCTGTCTCCAAAAC
NOV4i, 13376545
Protein Sequence	SEQ ID NO: 54	132 aa	MW at 15380.5kD
MYLDTPRYRGRSYHDRKSKVDLDRLNDDAKRYSCTPRNYSVNIREELKLANVVFFPRYLLVQRCGGNC
GCGTVNWRSCTCNSGKTVKKYHEVLQFEPGHIKRRGRAKTMALVDIQLDHHERCDCICSSRPPR

[0398] The NOV4j 13376544 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 4F.

TABLE 4F
NOV4j Sequence Analysis
NOV4j, 13376544	SEQ ID NO: 55	1587 bp
DNA Sequence	ORF Start: ATG at 540	ORF Stop: end of sequence
AGAGGCTCTCAAATTAGATCAAGAAATGCCTTTAACAGAAGTGAAGAGTGAACCTGCTCCTGACATGG
CCGCTTCACTCTCAGGAGAATACACGGATACAGCTAGTGTTTGACAATCAGTTTGCATTAGAGGAAGC
AGAAAATGATATCTGTAGGTATGATTTTGTGGAAGTTGAAGATATATCCGAAACCAGTACCATTATTA
GAGGACGATGGTGTGGACACAAGGAAGTTCCTCCAAGGATAAAATCAAGAACGAACCAAATTAAAATC
ACATTCAAGTCCGATGACTACTTTGTGGCTAAACCTGGATTCAAGATTTATTATTCTTTGCTGGAAGA
TTTCCAACCCGCAGCAGCTTCAGAGACCAACTGGGAATCTGTCACAAGCTCTATTTCAGGGGTATCCT
ATAACTCTCCATCAGTAACGGATCCCACTCTGATTGCCGATGCTCTGGACAAAAAAATTGCAGAATTT
GATACAGTGGAAGATCTGCTCAAGTACTTCAATCCAGAGTCATGGCAAGAAGATCTTGAGAATATGTA
TCTGGACACCCCTCGGTATCGAGGCAGGTCATACCATGACCGGAAGTCAAAAGTTGACCTGGATAGGC
TCAATGATGATGCCAACCGTTACAGTTGCACTCCCAGGAATTACTCGGTCAATATAAGAGAAGAGCTG
AAGTTGGCCAATGTGGTCTTCTTTCCACGTTGCCTCCTCGTGCAGCGCTGTGGAGGAAATTGTGACTG
TGGAACTGTCAACTGGAGGTCCTGCACATGCAATTCAGGGAAAACCGTGAAAAAGTATCATGAGGTAT
TACAGTTTGAGCCTGGCCACATCAAGAGGAGGGGTAGAGCTAAGACCATGGCTCTAGTTGACATCCAG
TTGGATCACCATGAACGATGTGATTGTATCTGCAGCTCAAGACCACCTCGATAAGAGAATGTGCACAT
CCTTACATTAAGCCTGAAAGAACCTTTAGTTTAAGGAGGGTGAGATAAGAGACCCTTTTCCTACCAGC
AACCAAACTTACTACTAGCCTGCAATGCAATGAACACAAGTGGTTGCTGAGTCTCAGCCTTGCTTTGT
TAATGCCATGGCAAGTAGAAAGGTATATCATCAACTTCTATACCTAAGAATATAGGATTGCATTTAAT
AATAGTGTTTGAGGTTATATATGCACAAACACACACAGAAATATATTCATGTCTATGTGTATATAGAT
CAAATGTTTTTTTTGGTATATATAACCAGGTACACCAGAGCTTACATATGTTTGAGTTAGACTCTTAA
AATCCTTTGCCAAAATAAGGGATGGTCAAATATATGAAACATGTCTTTAGAAAATTTAGGAGATAAAT
TTATTTTTAAATTTTGAAACACAAAACAATTTTGAATCTTGCTCTCTTAAAGAAAGCATCTTGTATAT
TAAAAATCAAAAGATGAGGCTTTCTTACATATACATCTTAGTTGATTATTAAAAAAGGAAAAATATGG
TTTCCAGAGAAAAGGCCAATACCTAACCATTTTTTCCATGAGAAGCACTGCATACTTACCTATGTGGA
CTATAATAACCTGTCTCCAAAAC
NOV4j, 13376544
Protein Sequence	SEQ ID NO: 56	132 aa	MW at 15380.5kD
MYLDTPRYRGRSYHDRKSKVDLDRLNDDAKRYSCTPRNYSVNIREELKLANVVFFPRCLLVQRCGGNC
DCGTVNWRSCTCNSGKTVKKYHEVLQFEPGHIKRRGRAKTMALVDIQLDHHERCDCICSSRPPR

[0399] The NOV4k 13376543 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 4G.

TABLE 4G
NOV4k Sequence Analysis
NOV4k, 13376543	SEQ ID NO: 57	1587 bp
DNA Sequence	ORF Start: ATG at 540	ORF Stop: end of sequence
AGAGGCTCTCAAATTAGATCAAGAAATGCCTTTAACAGAAGTGAAGAGTGAACCTGCTCCTGACATGG
CGGCTTCACTCTCAGGAGAATACACGGATACAGCTAGTGTTTGACAATCAGTTTGGATTAGAGGAAGC
AGAAAATGATATCTGTAGGTATGATTTTGTGGAAGTTGAAGATATATCCGAAACCAGTACCATTATTA
GAGGACGATGGTGTGGACACAAGGAAGTTCCTCCAAGGATAAAATCAAGAACGAACCAAATTAAAATC
ACATTCAAGTCCGATGACTACTTTGTGGCTAAACCTGGATTCAAGATTTATTATTCTTTGCTGGAAGA
TTTCCAACCCGCAGCAGCTTCAGAGACCAACTGGGAATCTGTCACAAGCTCTATTTCAGGGGTATCCT
ATAACTCTCCATCAGTAACGGATCCCACTCTGATTGCGGATGCTCTGGACAAAAAAATTGCAGAATTT
GATACAGTGGAAGATCTGCTCAAGTACTTCAATCCAGAGTCATGGCAAGAAGATCTTGAGAATATGTA
TCTGGACACCCCTCGGTATCGAGGCAGGTCATACCATGACCGGAAGTCAAAAGTTGACCTGGATAGGC
TCAATGATGATGCCAAGCGTTACAGTTGCACTCCCAGGAATTACTCGGTCAATATAAGAGAAGAGCTG
AAGTTGGCCAATGTGGTCTTCTTTCCACGTTGCCTCCTCGTGCAGCGCTGTGGAGGAAATTGTGGCTG
TGGAACTGTCAACTGGAGGTCCTGCACATGCAATTCAGGGAAAACCGTGAAAAAGTATCATGAGGTAT
TACAGTTTGAGCCTGGCCACATCAAGAGGAGGGGTAGAACTAAGACCATGGCTCTAGTTGACATCCAG
TTGGATCACCATGAACGATGTGATTGTATCTGCAGCTCAAGACCACCTCGATAAGAGAATGTGCACAT
CCTTACATTAAGCCTGAAAGAACCTTTAGTTTAAGGAGGGTGAGATAAGAGACCCTTTTCCTACCAGC
AACCAAACTTACTACTAGCCTGCAATGCAATGAACACAAGTGGTTGCTGAGTCTCAGCCTTGCTTTGT
TAATGCCATGGCAAGTAGAAAGGTATATCATCAACTTCTATACCTAAGAATATAGGATTGCATTTAAT
AATAGTGTTTGAGGTTATATATGCACAAACACACACAGAAATATATTCATGTCTATGTGTATATAGAT
CAAATGTTTTTTTTGGTATATATAACCAGGTACACCAGAGCTTACATATGTTTGAGTTAGACTCTTAA
AATCCTTTGCCAAAATAAGGGATGGTCAAATATATGAAACATGTCTTTAGAAAATTTAGGAGATAAAT
TTATTTTTAAATTTTGAAACACAAAACAATTTTGAATCTTGCTCTCTTAAAGAAAGCATCTTGTATAT
TAAAAATCAAAAGATGAGGCTTTCTTACATATACATCTTAGTTGATTATTAAAAAAGGAAAAATATGG
TTTCCAGAGAAAAGGCCAATACCTAAGCATTTTTTCCATGAGAAGCACTGCATACTTACCTATGTGGA
CTATAATAACCTGTCTCCAAAAC
NOV4k, 13376543
Protein Sequence	SEQ ID NO: 58	132 aa	MW at 15380.5kD
MYLDTPRYRGRSYHDRKSKVDLDRLNDDAKRYSCTPRNYSVNIREELKLANVVFFPRCLLVQRCGGNC
GCGTVNWRSCTCNSGKTVKKYHEVLQFEPGHIKRRGRTKTMALVDIQLDHHERCDCICSSRPPR

[0400] The NOV41 13376542 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 4H.

TABLE 4H
NOV4l Sequence Analysis
NOV4l, 13376542	SEQ ID NO: 59	1587 bp
DNA Sequence	ORF Start: ATG at 540	ORF Stop: end of sequence
AGAGGCTCTCAAATTAGATCAAGAAATCCCTTTAACAGAAGTGAAGAGTGAACCTGCTCCTGACATGG
CGGCTTCACTCTCAGGAGAATACACGGATACAGCTAGTGTTTGACAATCAGTTTGGATTAGAGGAAGC
AGAAAATGATATCTGTAGGTATGATTTTGTGGAAGTTGAAGATATATCCGAAACCAGTACCATTATTA
CAGGACGATGGTGTGGACACAAGGAAGTTCCTCCAAGGATAAAATCAAGAACGAACCAAATTAAAATC
ACATTCAAGTCCGATGACTACTTTGTGGCTAAACCTGGATTCAAGATTTATTATTCTTTGCTGGAAGA
TTTCCAACCCGCAGCAGCTTCAGAGACCAACTGGGAATCTGTCACAAGCTCTATTTCAGGGGTATCCT
ATAACTCTCCATCAGTAACGGATCCCACTCTGATTGCGGATGCTCTGGACAAAAAAATTGCAGAATTT
GATACAGTGGAAGATCTGCTCAAGTACTTCAATCCAGAGTCATGGCAAGAAGATCTTGAGAATATGTA
TCTGGACACCCCTCGGTATCGAGGCAGGTCATACCATGACCGGAAGTCAAAAGTTGACCTGGATAGGC
TCAATGATGATGCCAACCGTTACAGTTGCACTCCCAGGAATTACTCGGTCAATATAAGAGAAGAGCTG
AAGTTGGCCAATGTGGTCTTCTTTCCACGTTGCCTCCTCGTGCAGCGCTGTGGAGGAAATTGTGGCTG
TGGAACTGTCAACTGGAGGTCCTGCACATGCAATTCAGGGAAAACCGTGAAAAAGTATCATGAGGTAT
TACAGTTTGAGCCTGGCCACATCAAGAGGAGGGGTAGAGTTAAGACCATGGCTCTAGTTGACATCCAG
TTGGATCACCATGAACGATGTGATTGTATCTGCAGCTCAAGACCACCTCGATAAGAGAATGTGCACAT
CCTTACATTAAGCCTGAAAGAACCTTTAGTTTAAGGAGGGTGAGATAAGAGACCCTTTTCCTACCAGC
AACCAAACTTACTACTAGCCTGCAATGCAATGAACACAAGTGGTTGCTGAGTCTCAGCCTTGCTTTGT
TAATGCCATGGCAAGTAGAAAGGTATATCATCAACTTCTATACCTAAGAATATAGGATTGCATTTAAT
AATAGTGTTTGAGGTTATATATGCACAAACACACACAGAAATATATTCATGTCTATGTGTATATAGAT
CAAATGTTTTTTTTGGTATATATAACCAGGTACACCAGAGCTTACATATGTTTGAGTTAGACTCTTAA
AATCCTTTGCCAAAATAAGGGATGGTCAAATATATGAAACATGTCTTTAGAAAATTTAGGAGATAAAT
TTATTTTTAAATTTTGAAACACAAAACAATTTTGAATCTTGCTCTCTTAAAGAAAGCATCTTGTATAT
TAAAAATCAAAAGATGAGGCTTTCTTACATATACATCTTAGTTGATTATTAAAAAAGGAAAAATATGG
TTTCCAGAGAAAAGGCCAATACCTAAGCATTTTTTCCATGAGAAGCACTGCATACTTACCTATGTGGA
CTATAATAACCTGTCTCCAAAAC
NOV4l, 13376542
Protein Sequence	SEQ ID NO: 60	132 aa	MW at 15380.5kD
MYLDTPRYRGRSYHDRKSKVDLDRLNDDAKRYSCTPRNYSVNIREELKLANVVFFPRCLLVQRCGGNC
GCGTVNWRSCTCNSGKTVKKYHEVLQFEPGHIKRRGRVKTMALVDIQLDHHERCDCICSSRPPR

[0401] The NOV4m 13376541 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 41.

TABLE 4I
NOV4m Sequence Analysis
NOV4m, 13376541	SEQ ID NO: 61	1587 bp
DNA Sequence	ORF Start: ATG at 540	ORF Stop: end of sequence
AGAGGCTCTCAAATTAGATCAAGAAATGCCTTTAACAGAAGTGAAGAGTGAACCTGCTCCTGACATGG
CGGCTTCACTCTCAGGAGAATACACGGATACAGCTAGTGTTTGACAATCAGTTTGGATTAGAGGAAGC
AGAAAATGATATCTGTAGGTATGATTTTGTGGAAGTTGAAGATATATCCGAAACCAGTACCATTATTA
GAGGACGATGGTGTGGACACAAGGAAGTTCCTCCAAGGATAAAATCAAGAACGAACCAAATTAAAATC
ACATTCAAGTCCGATGACTACTTTGTGGCTAAACCTGGATTCAAGATTTATTATTCTTTGCTGGAAGA
TTTCCAACCCGCAGCAGCTTCAOAGACCAACTGGGAATCTGTCACAAGCTCTATTTCACGGGTATCCT
ATAACTCTCCATCAGTAACGGATCCCACTCTGATTGCGGATCCTCTGGACAAAAAAATTGCAGAATTT
GATACAGTGGAAGATCTGCTCAAGTACTTCAATCCAGAGTCATGGCAAGAAGATCTTGAGAATATGTA
TCTGGACACCCCTCGGTATCGAGGCAGGTCATACCATGACCGGAAGTCAAAAGTTGACCTGGATAGGC
TCAATGATGATGCCAAGCGTTACAGTTGCACTCCCAGGAATTACTCGGTCAATATAAGAGAAGAGCTG
AAGTTGGCCAATGTGGTCTTCTTTCCACGTTGCCTCCTCGTGCAGCGCTGTGGAGGAAATTGTGGCTG
TGGAACTGTCAACTGGAGGTCCTGCACATGCAATTCAGGGAAAACCGTGAAAAAGTATCATGAGGTAT
TACAGTTTGAGCCTGGCCACATCAAGAGGAGGGGTAGAGCTAAGACCATGGCTCTAGTTGGCATCCAG
TTGGATCACCATGAACGATGTGATTGTATCTGCAGCTCAAGACCACCTCGATAAGAGAATGTGCACAT
CCTTACATTAAGCCTGAAAGAACCTTTAGTTTAAGGACGGTGAGATAAGAGACCCTTTTCCTACCAGC
AACCAAACTTACTACTAGCCTGCAATGCAATGAACACAAGTGGTTGCTGAGTCTCAGCCTTGCTTTGT
TAATGCCATGGCAAGTAGAAAGGTATATCATCAACTTCTATACCTAAGAATATAGGATTGCATTTAAT
AATAGTGTTTGAGGTTATATATGCACAAACACACACAGAAATATATTCATGTCTATGTGTATATAGAT
CAAATGTTTTTTTTGGTATATATAACCAGGTACACCAGAGCTTACATATGTTTGAGTTAGACTCTTAA
AATCCTTTGCCAAAATAAGGGATGGTCAAATATATGAAACATGTCTTTAGAAAATTTAGGAGATAAAT
TTATTTTTAAATTTTGAAACACAAAACAATTTTCAATCTTGCTCTCTTAAAGAAACCATCTTGTATAT
TAAAAATCAAAAGATGAGGCTTTCTTACATATACATCTTAGTTGATTATTAAAAAAGGAAAAATATGG
TTTCCAGAGAAAAGGCCAATACCTAAGCATTTTTTCCATGAGAAGCACTGCATACTTACCTATGTGGA
CTATAATAACCTGTCTCCAAAAC
NOV4m, 13376541
Protein Sequence	SEQ ID NO: 62	132 aa	MW at 15380.5kD
MYLDTPRYRGRSYHDRKSKVDLDRLNDDAKRYSCTPRNYSVNIREELKLANVVFFPRCLLVQRCGGNC
GCGTVNWRSCTCNSGKTVKKYHEVLQFEPGHIKRRGRAKTMALVGIQLDHHERCDCICSSRPPR

[0402] Further analysis of the NOV4a protein yielded the following properties shown in Table 4N.

TABLE 4N
Protein Sequence Properties NOV4a
SignalP analysis:	No Known Signal Sequence Predicted
PSORT II analysis:
PSG:	a new signal peptide prediction method
	N-region: length 11; pos.chg 3; neg.chg 1
	H-region: length 3; peak value −21.76
	PSG score: −26.16
GvH:	von Heijne's method for signal seq. recognition
	GvH score (threshold: −2.1): −7.79
	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:  0
	number of TMS(s) . . . fixed
	PERIPHERAL Likelihood = 4.51 (at 49)
	ALOM score:  4.51 (number of TMSs: 0)
MITDISC: discrimination of mitochondrial targeting seq
	R content:	3	Hyd Moment(75):	5.50
	Hyd Moment(95):	9.22	G content:	1
	D/E content:	2	S/T content:	2
	Score: −3.90
Gavel: prediction of cleavage sites for mitochondrial preseq
	R-3 motif at 40 PRNY|S
NUCDISC: discrimination of nuclear localization signals
	pat4: none
	pat7: PGHIKRR (3) at 97
	bipartite: KKYHEVLQFEPGHIKRR at  87
	content of basic residues: 19.7%
	NLS Score: 0.28
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: 94.1
COIL:	Lupas's algorithm to detect coiled-coil regions
	total: 0 residues
Final Results (k = 9/23):
87.0%: nuclear
13.0%: mitochondrial
>> prediction for CG52053-01 is nuc (k = 23)

[0403] PFam analysis predicts that the NOV4a protein contains the domains shown in the Table 4O.

TABLE 4O
Domain Analysis of NOV4a
		Identities/
	NOV4a	Similarities for
Pfam Domain	Match Region	the Matched Region	Expect Value
PDGF	34 . . . 124	25/94 (27%)	0.023
		43/94 (46%)
Metallothio_2	64 . . . 127	19/88 (22%)	0.28
		36/88 (41%)

Example 5. NOV 5, CG52676: T cell immunoglobulin mucin-3.

[0404] The NOV5 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 5A.

TABLE 5A
NOV5 Sequence Analysis
NOV5a, CG52676-02	SEQ ID NO: 63	1203 bp
DNA Sequence	ORF Start: ATG at 587	ORF Stop: end of sequence
GGAAGAAGAAGGAGGAGGAGGAGAAGGAGAAGAAGAAGGAGAAGAACGCAAGACTTCGTCTCAAAAAA
AAAGAAGAAAAAATTTAAATACATTTAAAAAAGAAGGTTGCATGCTGTGGAGCAACCAGACAATTGTG
ATGAAATGTGAAGCACAAGGCACCAGCTGTGACGTGTTTTTGCCAAGAAGTCAAACCACGTTCCAACT
AAACCTCTAGAGCAAACTTTCATTTTCAGCAAATTCGAAGAAAAGAGGAATAATGTAAATGACCCCAC
AGGGAAACAGACAAACCCTGAATGTGGAGCATTTCACAGGACAAAACCTGGACAGACATCGGAACACT
TACAGGATGTGTGTAGTGTGGCATGACAGAGAACTTTGGTTTCCTTTAATGTGACTGTAGACCTGGCA
GTGTTACTATAAGAATCACTGGCAATCAGACACCCGGGTGTGCTGAGCTGGCACTCAGTGGGGGCGGC
TACTGCTCATGTGATTGTGGAGTAGACAGTTGGAAGAAGTACCCAGTCCATTTGGAGAGTTAAAACTG
TGCCTAACAGAGGTGTCCTCTGACTTTTCTTCTGCAAGCTCCATGTTTTCACATCTTCCCTTTGACTG
TGTCCTGCTGCTGCTGCTGCTACTACTTACAAGGTCCTCAGAAGTGGAATACAGAGCGGAGGTCGGTC
AGAATGCCTATCTGCCCTGCTTCTACACCCCAGCCGCCCCAGGGAACCTCGTGCCCGTCTGCTGGGGC
AAAGGAGCCTGTCCTGTGTTTGAATGTGGCAACGTGGTGCTCAGGACTGATGAAAGGGATGTGAATTA
TTGGACATCCAGATACTGGCTAAATGGGGATTTCCGCAAAGGAGATGTGTCCCTGACCATAGAGAATG
TGACTCTACCAGACAGTGGGATCTACTGCTGCCGGATCCAAATCCCAGGCATAATGAATGATGAAAAA
TTTAACCTGAAGTTGGTCATCAAACCAGGTGAGTGGACATTTGCATGCCATCTTTATGAATAAGATTT
ATCTGTGGATCATATTAAAGGTACTGATTGTTCTCATCTCTGACTTCCCTAATTATAGCCCTGGAGGA
GGGCCACTAAGACCTAAAGTTTAACAGGCCCCATTGGTGATGCTCAGTGATATTTAACACCTTCTCTC
TGTTTTAAAACTCATGGGTGTGCCTGGGCGTGGTGGCTCACACCTCT
NOV5a, CG52676-02
Protein Sequence	SEQ ID NO: 64	142 aa	MW at 16148.5kD
MFSHLPFDCVLLLLLLLLTRSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECGNVVL
RTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPGEWTF
ACHLYE
NOV5b, 191998702	SEQ ID NO: 65	375 bp
DNA Sequence	ORF Start: at 1	ORF Stop: end of sequence
AAGCTTTCAGAAGTGGAATACAGAGCGGAGGTCGGTCAGAATGCCTATCTGCCCTGCTTCTACACCCC
AGCCGCCCCAGGGAACCTCGTGCCCGTCTGCTGGGGCAAAGGAGCCTGTCCTGTGTTTGAATGTGGCA
ACGTGGTGCTCAGGACTGATGAAAGGGATGTGAATTATTGGACATCCAGATACTGGCTAAATGGGGAT
TTCCGCAAAGGAGATGTGTCCCTGACCATAGAGAATGTGACTCTAGCAGACAGTGGGATCTACTGCTG
CCGGATCCAAATCCCAGGCATAATGAATGATGAAAAATTTAACCTGAAGTTGGTCATCAAACCAGGTG
AGTGGACATTTGCATGCCATCTTTATGAACTCGAG
NOV5b, 191998702
Protein Sequence	SEQ ID NO: 66	125 aa	MW at 14205.1kD
KLSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECGNVVLRTDERDVNYWTSRYWLNGD
FRKGDVSLTIENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPGEWTFACHLYELE
NOV5c, CG52676-01	SEQ ID NO: 67	1203 bp
DNA Sequence	ORF Start: ATG at 587	ORF Stop: end of sequence
GGAAGAAGAAGGAGGAGGAGGAGAAGGAGAAGAAGAAGGAGAAGAACGCAAGACTTCGTCTCAAAAAA
AAAGAAGAAAAAATTTAAATACATTTAAAAAAGAAGGTTGCATGCTGTGGAGCAACCAGACAATTGTG
ATGAAATGTGAAGCACAAGGCACCAGCTGTGACGTGTTTTTGCCAAGAAGTCAAACCACGTTCCAACT
AAACCTCTAGAGCAAACTTTCATTTTCAGCAAATTCGAAGAAAAGAGGAATAATGTAAATGACCCCAC
AGGGAAACAGACAAACCCTGAATGTGGAGCATTTCACAGGACAAAACCTGGACAGACATCGGAACACT
TACAGGATGTGTGTAGTGTGGCATGACAGAGAACTTTGGTTTCCTTTAATGTGACTGTAGACCTGGCA
GTGTTACTATAAGAATCACTGGCAATCAGACACCCGGGTGTGCTGAGCTGCCACTCAGTGGGGGCGGC
TACTGCTCATGTGATTGTGGAGTACACAGTTGGAAGAAGTACCCAGTCCATTTGGAGAGTTAAAACTG
TGCCTAACAGAGGTGTCCTCTGACTTTTCTTCTGCAAGCTCCATGTTTTCACATCTTCCCTTTGACTG
TGTCCTGCTGCTGCTGCTGCTACTACTTACAAGGTCCTCAGAAGTGGAATACACAGCGGAGGTCGGTC
AGAATGCCTATCTGCCCTGCTTCTACACCCCAGCCGCCCCAGGGAACCTCGTGCCCGTCTGCTGGGGC
AAAGGAGCCTGTCCTGTGTTTGAATGTGGCAACGTGGTGCTCAGGACTGATGAAAGGGATGTGAATTA
TTGGACATCCAGATACTGGCTAAATGGGGATTTCCGCAAAGGAGATGTGTCCCTGACCATAGAGAATG
TGACTCTAGCAGACAGTGGGATCTACTGCTGCCGGATCCAAATCCCAGGCATAATGAATGATGAAAAA
TTTAACCTGAAGTTGGTCATCAAACCAGGTGAGTGGACATTTGCATGCCATCTTTATGAATAAGATTT
ATCTGTGGATCATATTAAAGGTACTGATTGTTCTCATCTCTGACTTCCCTAATTATAGCCCTGGAGGA
GGGCCACTAAGACCTAAAGTTTAACAGGCCCCATTGGTGATGCTCAGTGATATTTAACACCTTCTCTC
TGTTTTAAAACTCATGGGTGTGCCTGGGCGTGGTGGCTCACACCTCT
NOV5c, CG52676-01
Protein Sequence	SEQ ID NO: 68	142 aa	MW at 16148.5kD
MFSHLPFDCVLLLLLLLLTRSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECGNVVL
RTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPGEWTF
ACHLYE
NOV5d, CG52676-03	SEQ ID NO: 69	375 bp
DNA Sequence	ORF Start: at 7	ORF Stop: end of sequence
AAGCTTTCAGAAGTGGAATACAGAGCGGAGGTCGGTCAGAATGCCTATCTGCCCTGCTTCTACACCCC
AGCCGCCCCAGGGAACCTCGTGCCCGTCTGCTGGGGCAAAGGAGCCTGTCCTGTGTTTGAATGTGGCA
ACGTGGTGCTCAGGACTGATGAAAGGGATGTGAATTATTGGACATCCAGATACTGGCTAAATGGGGAT
TTCCGCAAAGGAGATGTGTCCCTGACCATAGAGAATGTGACTCTAGCAGACAGTGGCATCTACTGCTG
CCGGATCCAAATCCCAGGCATAATGAATGATGAAAAATTTAACCTGAAGTTGGTCATCAAACCAGGTG
AGTGGACATTTGCATGCCATCTTTATGAACTCGAG
NOV5d, CG52676-03
Protein Sequence	SEQ ID NO: 70	121 aa	MW at 13721.5kD
SEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECGNVVLRTDERDVNYWTSRYWLNGDFR
KGDVSLTIENVTLADSGIYCCRIQIPGIMNDEKFNLKLVIKPGEWTFACHLYE

[0405] The NOV5e 13382222 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 5B.

TABLE 5B
NOV5e Sequence Analysis
NOV5e, 13382222	SEQ ID NO: 71	1203 bp
DNA Sequence	ORF Start: ATG at 587	ORF Stop: end of sequence
GGAAGAAGAAGGAGGAGGAGGAGAAGGAGAAGAAGAAGGAGAAGAACGCAAGACTTCGTCTCAAAAAA
AAAGAAGAAAAAATTTAAATACATTTAAAAAAGAAGGTTGCATGCTGTGGAGCAACCAGACAATTGTG
ATGAAATGTGAAGCACAAGGCACCAGCTGTGACGTGTTTTTGCCAAGAAGTCAAACCACGTTCCAACT
AAACCTCTAGAGCAAACTTTCATTTTCAGCAAATTCGAAGAAAAGAGGAATAATGTAAATGACCCCAC
AGGGAAACAGACAAACCCTGAATGTGGAGCATTTCACAGGACAAAACCTCGACAGACATCGGAACACT
TACAGGATGTGTGTAGTGTGGCATGACAGAGAACTTTGGTTTCCTTTAATGTGACTGTAGACCTGGCA
GTGTTACTATAAGAATCACTGGCAATCAGACACCCGGGTGTGCTGAGCTGGCACTCAGTGGGCGCGGC
TACTGCTCATGTGATTGTGGAGTAGACAGTTGGAAGAAGTACCCAGTCCATTTGGAGAGTTAAAACTG
TGCCTAACAGAGGTGTCCTCTGACTTTTCTTCTGCAACCTCCATGTTTTCACATCTTCCCTTTGACTG
TGTCCTGCTGCTGCTGCTGCTACTACTTACAAGGTCCTCAGAAGTGGAATACAGAGCGGAGGTCGGTC
AGAATGCCTATCTGCCCTGCTTCTACACCCCAGCCGCCCCAGGGAACCTCGTGCCCGTCTGCTGGGGC
AAAGGAGCCTGTCCTGTGTTTGAATGTGGCAACGTGGTGCTCAGGACTGATGAAAGGGATGTGAATTA
TTGGACATCCAGATACTGGCTAAATGGGGATTTCCGCAAAGGAGATGTGTCCCTGACCATATAGAATG
TGACTCTAGCAGACAGTGGGATCTACTGCTGCCGGATCCAAATCCCACGCATAATGAATGATGAAAAA
TTTAACCTGAAGTTGGTCATCAAACCAGGTGAGTGCACATTTGCATGCCATCTTTATGAATAAGATTT
ATCTGTGGATCATATTAAAGGTACTGATTGTTCTCATCTCTGACTTCCCTAATTATAGCCCTGGAGGA
GGGCCACTAAGACCTAAAGTTTAACAGGCCCCATTGGTGATGCTCAGTGATATTTAACACCTTCTCTC
TGTTTTAAAACTCATGGGTGTGCCTGGGCGTGGTGGCTCACACCTCT
NOV5e, 13382222
Protein Sequence	SEQ ID NO: 72	97 aa
MFSHLPFDCVLLLLLLLLTRSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPVFECGNVVL
RTDERDVNYWTSRYWLNGDFRKGDVSLTI

[0406] A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 5C.

TABLE 5C
Comparison of the NOV5 protein sequences.
NOV5a MFSHLPFDCVLLLLLLLLTRSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPV
NOV5b -------------------KLSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPV
NOV5c MFSHLPFDCVLLLLLLLLTRSSEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPV
NOV5d ---------------------SEVEYRAEVGQNAYLPCFYTPAAPGNLVPVCWGKGACPV
NOV5a FECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIPGIMND
NOV5b FECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIPGIMND
NOV5c FECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIPGIMND
NOV5d FECGNVVLRTDERDVNYWTSRYWLNGDFRKGDVSLTIENVTLADSGIYCCRIQIPGIMND
NOV5a EKFNLKLVIKPGEWTFACHLYE--
NOV5b EKFNLKLVIKPGEWTFACHLYELE
NOV5c EKFNLKLVIKPGEWTFACHLYE--
NOV5d EKFNLKLVIKPGEWTFACHLYE--
NOV5a (SEQ ID NO:64)
NOV5b (SEQ ID NO:66)
NOV5c (SEQ ID NO:68)
NOV5d (SEQ ID NO:70)

[0407] Further analysis of the NOV5a protein yielded the following properties shown in Table 5D.

TABLE 5D
Protein Sequence Properties NOV5
SignalP analysis:	Cleavage site between residues 22 and 23
PSORT II analysis:
PSG:	a new signal peptide prediction method
	N-region: length 8; pos.chg 0; neg.chg 1
	H-region: length 11; peak value 0.00
	PSG score: −4.40
GvH:	von Heijne's method for signal seq. recognition
	GvH score (threshold: −2.1):  5.66
	possible cleavage site: between 21 and 22
>>> 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 = −5.57 Transmembrane  2-18
	PERIPHERAL Likelihood = 5.89 (at 48)
	ALOM score: −5.57 (number of TMSs: 1)
MTOP:	Prediction of membrane topology (Hartmann et al.)
	Center position for calculation: 9
	Charge difference: −1.5 C(−1.0) − N(0.5)
	N >= C: N-terminal side will be inside
>>> membrane topology: type 2  (cytoplasmic tail 1 to 2)
MITDISC: discrimination of mitochondrial targeting seq
	R content:	1	Hyd Moment(75):	8.78
	Hyd Moment(95):	7.11	G content:	0
	D/E content:	2	S/T content: 4
	Score: −4.44
Gavel: prediction of cleavage sites for mitochondrial preseq
	R-2 motif at 30 TRS|SE
NUCDISC: discrimination of nuclear localization signals
	pat4: none
	pat7: none
	bipartite: none
	content of basic residues: 8.5%
	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: 94.1
COIL:	Lupas's algorithm to detect coiled-coil regions
	total: 0 residues
Final Results (k = 9/23):
30.4%: cytoplasmic
26.1%: mitochondrial
13.0%: Golgi
8.7%: vacuolar
8.7%: endoplasmic reticulum
4.3%: extracellular, including cell wall
4.3%: nuclear
4.3%: vesicles of secretory system
>> prediction for CG52676-02 is cyt (k = 23)

Example 6. NOV 6, CG52997: LRR containing protein

[0408] The NOV6 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 6A.

TABLE 6A
NOV6 Sequence Analysis
NOV6a, CG52997-01	SEQ ID NO: 73	2838 bp
DNA Sequence	ORF Start: ATG at 184	ORF Stop: end of sequence
AACTTTATGAAGCTATGGGACTTGACAAAAAGTGATATTTGAGAAGAAAGTACGCAGTGGTTGGTGTT
TTCTTTTTTTTAATAAAGGAATTGAATTACTTTGAACACCTCTTCCAGCTGTGCATTACAGATAACGT
CAGGAAGAGTCTCTGCTTTACAGAATCGGATTTCATCACATGACAACATGAAGCTGTGGATTCATCTC
TTTTATTCATCTCTCCTTGCCTGTATATCTTTACACTCCCAAACTCCAGTGCTCTCATCCAGAGGCTC
TTGTGATTCTCTTTGCAATTGTGAGGAAAAAGATGGCACAATCGTAATAAATTGTGAAGCAAAAGGTA
TCAAGATGGTATCTGAAATAAGTGTGCCACCATCACGACCTTTCCAACTAAGCTTATTAAATAACGGC
TTGACGATGCTTCACACAAATGACTTTTCTGGGCTTACCAATCCTATTTCAATACACCTTGGATTTAA
CAATATTGCAGATATTGAGATAGGTGCATTTAATGGCCTTGGCCTCCTGAAACAACTTCATATCAATC
ACAATTCTTTAGAAATTCTTAAAGAGGATACTTTCCATGGACTGGAAAACCTGGAATTCCTGCAAGCA
GATAACAATTTTATCACAGTGATTGAACCAAGTGCCTTTAGCAAGCTCAACAGACTCAAAGTGTTAAT
TTTAAATGACAATGCTATTGAGAGTCTTCCTCCAAACATCTTCCGATTTGTTCCTTTAACCCATCTAG
ATCTTCGTGGAAATCAATTACAAACATTGCCTTATGTTGGTTTTCTCGAACACATTGGCCGAATATTG
GATCTTCAGTTGGAGGACAACAAATGGGCCTGCAATTGTGACTTATTGCAGTTAAAAACTTGGTTGGA
GAACATGCCTCCACAGTCTATAATTGGTGATGTTGTCTGCAACAGCCCTCCATTTTTTAAAGGAAGTA
TACTCAGTAGACTAAAGAAGGAATCTATTTGCCCTACTCCACCAGTGTATGAAGAACATGAGGATCCT
TCAGGATCATTACATCTGGCAGCAACATCTTCAATAAATGATAGTCGCATGTCAACTAAGACCACGTC
CATTCTAAAACTACCCACCAAAGCACCAGGTTTGATACCTTATATTACAAACCCATCCACTCAACTTC
CAGGACCTTACTGCCCTATTCCTTGTAACTGCAAAGTCCTATCCCCATCAGGACTTCTAATACATTGT
CAGGAGCGCAACATTGAAAGCTTATCAGATCTGAGACCTCCTCCGCAAAATCCTAGAAAGCTCATTCT
AGCGGGAAATATTATTCACAGTTTAATGAAGTCTGATCTAGTGGAATATTTCACTTTGGAAATGCTTC
ACTTGGGAAACAATCGTATTGAAGTTCTTGAAGAAGGATCGTTTATGAACCTAACGAGCTTACAAAAA
CTCTATCTAAATGGTAACCACCTGACCAAATTAAGTAAACGCATGTTCCTTGGTCTCCATAATCTTGA
ATACTTATATCTTGAATACAATGCCATTAAGGAAATACTGCCAGGAACCTTTAATCCAATGCCTAAAC
TTAAAGTCCTGTATTTAAATAACAACCTCCTCCAAGTTTTACCACCACATATTTTTTCAGGGGTTCCT
CTAACTAAGGTAAATCTTAAAACAAACCAGTTTACCCATCTACCTGTAAGTAATATTTTGGATGATCT
TGATTTACTAACCCAGATTGACCTTGAGGATAACCCCTGGGACTGCTCCTGTGACCTGGTTGGACTGC
AGCAATGGATACAAAAGTTAAGCAAGAACACAGTGACAGATGACATCCTCTCCACTTCCCCCGGGCAT
CTCGACAAAAACGAATTGAAAGCCCTAAATAGTGAAATTCTCTGTCCAGGTTTAGTAAATAACCCATC
CATGCCAACACAGACTAGTTACCTTATGGTCACCACTCCTGCAACAACAACAAATACGGCTGATACTA
TTTTACGATCTCTTACGGACGCTGTGCCACTGTCTGTTCTAATATTGGGACTTCTGATTATGTTCATC
ACTATTGTTTTCTGTGCTGCAGGGATAGTGGTTCTTGTTCTTCACCCCAGGAGAAGATACAAAAAGAA
ACAAGTAGATGAGCAAATGAGAGACAACAGTCCTGTGCATCTTCAGTACAGCATGTATGGCCATAAAA
CCACTCATCACACTACTGAAAGACCCTCTGCCTCACTCTATGAACAGCACATGGTGAGCCCCATGGTT
CATGTCTATAGAAGTCCATCCTTTGGTCCAAAGCATCTGGAAGAGGAAGAAGAGAGGAATGAGAAAGA
AGGAAGTGATGCAAAACATCTCCAAAGAAGTCTTTTGGAACAGGAAAATCATTCACCACTCACAGGGT
CAAATATGAAATACAAAACCACGAACCAATCAACAGAATTTTTATCCTTCCAAGATGCCAGCTCATTG
TACAGAAACATTTTAGAAAAAGAAAGGGAACTTCAGCAACTGGGAATCACAGAATACCTAAGGAAAAA
CATTGCTCAGCTCCAGCCTGATATGGAGGCACATTATCCTGGAGCCCACGAAGAGCTGAAGTTAATGG
AAACATTAATGTACTCACGTCCAAGGAAGGTATTAGTGGAACAGACAAAAAATGAGTATTTTGAACTT
AAAGCTAATTTACATGCTGAACCTGACTATTTAGAAGTCCTGGAGCAGCAAACATAGATGGAGAGTTT
GAGGGCTTTCGCAGAAATGCTGTGATTCTGTTTTAAGTCCATACCTTGTAAATTAGTGCCTTACGTGA
GTGTGTCATCCATCAGAACCTAAGCACAGCAGTAAACTATGGAGAAAAAA
NOV6a, CG52997-01
Protein Sequence	SEQ ID NO: 74	841 aa	MW at 95108.5kD
MKLWIHLFYSSLLACISLHSQTPVLSSRGSCDSLCNCEEKDGTMLINCEAKGIKMVSEISVPPSRPFQ
LSLLNNGLTMLHTNDFSGLTNAISIHLGFNNIADIEIGAFNGLGLLKQLHINHNSLEILKEDTFHGLE
NLEFLQADNNFITVIEPSAFSKLNRLKVLILNDNAIESLPPNIFRFVPLTHLDLRGNQLQTLPYVGFL
EHIGRILDLQLEDNKWACNCDLLQLKTWLENMPPQSIIGDVVCNSPPFFKGSILSRLKKESICPTPPV
YEEHEDPSGSLHLAATSSINDSRMSTKTTSILKLPTKAPGLIPYITKPSTQLPGPYCPIPCNCKVLSP
SGLLIHCQERNIESLSDLRPPPQNPRKLILAGNIIHSLMKSDLVEYFTLEMLHLGNNRIEVLEEGSFM
NLTRLQKLYLNGNHLTKLSKGMFLGLHNLEYLYLEYNAIKEILPGTFNPMPKLKVLYLNNNLLQVLPP
HIFSGVPLTKVNLKTNQFTHLPVSNILDDLDLLTQIDLEDNPWDCSCDLVGLQQWIQKLSKNTVTDDI
LCTSPGHLDKKELKALNSEILCPGLVNNPSMPTQTSYLMVTTPATTTNTADTILRSLTDAVPLSVLIL
GLLIMFITIVFCAAGIVVLVLHRRRRYKKKQVDEQMRDNSPVHLQYSMYGHKTTHHTTERPSASLYEQ
HMVSPMVHVYRSPSFGPKHLEEEEERNEKEGSDAKHLQRSLLEQENHSPLTGSNMKYKTTNQSTEFLS
FQDASSLYRNILEKERELQQLGITEYLRKNIAQLQPDMEAHYPGAHEELKLMETLMYSRPRKVLVEQT
KNEYFELKANLHAEPDYLEVLEQQT
NOV6b, CG52997-02	SEQ ID NO: 75	2531 bp
DNA Sequence	ORF Start: at 2	ORF Stop: end of sequence
GGATTCTCTCTTTTATTCATCTCTCCTTGCCTGTATATCTTTACACTCCCAAACTCCAGTGCTCTCAT
CCAGAGGCTCTTGTGATTCTCTTTGCAATTGTGAGGAAAAAGATGGCACAATGCTAATAAATTGTGAA
GCAAAAGGTATCAAGATGGTATCTGAAATAAGTGTGCTACCATCACGACCTTTCCAACTAAGCTTATT
AAATAACGGCTTGACGATGCTTCACACAAATGACTTTTCTGGGCTTACCAATGCTATTTCAATACACC
TTGGATTTAACAATATTGCAGATATTGAGATAGGTGCATTTAATGGCCTTGGCCTCCTGAAACAACTT
CATATCAATCACAATTCTTTAGAAATTCTTAAAGAGGATACTTTCCATGGACTGGAAAACCTGGAATT
CCTGCAAGCAGATAACAATTTTATCACAGTGATTGAACCAAGTGCCTTTAGCAAGCTCAACAGACTCA
AAGTGTTAATTTTAAATGACAATGCTATTGAGAGTCTTCCTCCAAACATCTTCCGATTTGTTCCTTTA
ACCCATCTAGATCTTCGTGGAAATCAATTACAAACATTGCCTTATGTTGGTTTTCTCGAACACATTGG
CCGAATATTGGATCTTCAGTTGGAGGACAACAAATGGGCCTGCAATTGTGACTTATTGCAGTTAAAAA
CTTGGTTGGAGAACATGCCTCCACAGTCTATAATTGGTGATGTTGTCTGCAACAGCCCTCCATTTTTT
AAAGGAAGTATACTCAGTAGACTAAAGAAGGAATCTATTTGCCCTACTCCACCAGTGTATGAAGAACA
TGAGGATCCTTCAGGATCATTACATCTGGCAGCAACATCTTCAATAAATGATAGTCGCATGTCAACTA
AGACCACGTCCATTCTAAAACTACCCACCAAAGCACCAGGTTTGATACCTTATATTACAAAGCCATCC
ACTCAACTTCCAGGACCTTACTGCCCTATTCCTTGTAACTGCAAAGTCCTATCCCCATCAGGACTTCT
AATACATTGTCAGGAGCGCAACATTGAAAGCTTATCAGATCTGAGACCTCCTCCGCAAAATCCTAGAA
AGCTCATTCTAGCGGGAAATATTATTCACAGTTTAATGAAGTCTGATCTAGTGGAATATTTCACTTTG
GAAATGCTTCACTTGGGAAACAATCGTATTGAAGTTCTTGAAGAAGGATCGTTTATGAACCTAACGAG
ATTACAAAAACTCTATCTAAATGGTAACCACCTGACCAAATTAAGTAAAGGCATGTTCCTTGGTCTCC
ATAATCTTGAATACTTATATCTTGAATACAATGCCATTAAGGAAATACTGCCAGGAACCTTTAATCCA
ATGCCTAAACTTAAAGTCCTGTATTTAAATAACAACCTCCTCCAAGTTTTACCACCACATATTTTTTC
AGGGGTTCCTCTAACTAAGGTAAATCTTAAAACAAACCAGTTTACCCATCTACCTGTAAGTAATATTT
TGGATGATCTTGATTTGCTAACCCAGATTGACCTTGAGGATAACCCCTGGGACTGCTCCTGTGACCTG
GTTGGACTGCAGCAATGGATACAAAAGTTAAGCAAGAACACAGTGACAGATGACATCCTCTGCACTTC
CCCCGGGCATCTCGACAAAAAGGAATTGAAAGCCCTAAATAGTGAAATTCTCTGTCCAGGTTTAGTAA
ATAACCCATCCATGCCAACACAGACTAGTTACCTTATGGTCACCACTCCTGCAACAACAACAAATACG
GCTGATACTATTTTACGATCTCTTACGGACGCTGTGCCACTGTCTGTTCTAATATTGGGACTTCTGAT
TATGTTCATCACTATTGTTTTCTGTGCTGCAGGGATAGTGGTTCTTGTTCTTCACCGCAGGAGAAGAT
ACAAAAAGAAACAAGTAGATGAGCAAATGAGAGACAACAGTCCTGTGCATCTTCAGTACAGCATGTAT
GGCCATAAAACCACTCATCACACTACTGAAAGACCCTCTGCCTCACTCTATGAACAGCACATGGTGAG
CCCCATGGTTCATGTCTATAGAAGTCCATCCTTTGGTCCAAAGCATCTGGAAGAGGAAGAAGAGAGGA
ATGAGAAAGAAGGAAGTGATGCAAAACATCTCCAAAGAAGTCTTTTGGAACAGGAAAATCATTCACCA
CTCACAGGGTCAAATATGAAATACAAAACCACGAACCAATCAACAGAATTTTTATCCTTCCAAGATGC
CAGCTCATTGTACAGAAACATTTTAGAAAAAGAAAGGGAACTTCAGCAACTGGGAATCACAGAATACC
TAAGGAAAAACATTGCTCAGCTCCAGCCTGATATGGAGGCACATTATCCTGGAGCCCACGAAGAGCTG
AAGTTAATGGAAACATTAATGTACTCACGTCCAAGGAAGGTATTAGTGGAACAGACAAAAAATGAGTA
TTTTGAACTTAAAGCTAATTTACATGCTGAACCTGACTATTTAGAAGTCCTGGAGCAGCAAACATAAG
GGCGAATTCTGCTGT
NOV6b, CG52997-02
Protein Sequence	SEQ ID NO: 76	837 aa	MW at 94517.6kD
DSLFYSSLLACISLHSQTPVLSSRGSCDSLCNCEEKDGTMLINCEAKGIKMVSEISVLPSRPFQLSLL
NNGLTMLHTNDFSGLTNAISIHLGFNNIADIEIGAFNGLGLLKQLHINHNSLEILKEDTFHGLENLEF
LQADNNFITVIEPSAFSKLNRLKVLILNDNAIESLPPNIFRFVPLTHLDLRGNQLQTLPYVGFLEHIG
RILDLQLEDNKWACNCDLLQLKTWLENMPPQSIIGDVVCNSPPFFKGSILSRLKKESICPTPPVYEEH
EDPSGSLHLAATSSINDSRMSTKTTSILKLPTKAPGLIPYITKPSTQLPGPYCPIPCNCKVLSPSGLL
IHCQERNIESLSDLRPPPQNPRKLILAGNIIHSLMKSDLVEYFTLEMLHLGNNRIEVLEEGSFMNLTR
LQKLYLNGNHLTKLSKGMFLGLHNLEYLYLEYNAIKEILPGTFNPMPKLKVLYLNNNLLQVLPPHIFS
GVPLTKVNLKTNQFTHLPVSNILDDLDLLTQIDLEDNPWDCSCDLVGLQQWIQKLSKNTVTDDILCTS
PGHLDKKELKALNSEILCPGLVNNPSMPTQTSYLMVTTPATTTNTADTILRSLTDAVPLSVLILGLLI
MFITIVFCAAGIVVLVLHRRRRYKKKQVDEQMRDNSPVHLQYSMYGHKTTHHTTERPSASLYEQHMVS
PMVHVYRSPSFGPKHLEEEEERNEKEGSDAKHLQRSLLEQENHSPLTGSNMKYKTTNQSTEFLSFQDA
SSLYRNILEKERELQQLGITEYLRKNIAQLQPDMEAHYPGAHEELKLMETLMYSRPRKVLVEQTKNEY
FELKANLHAEPDYLEVLEQQT
NOV6c, CG52997-03	SEQ ID NO: 77	1758 bp
DNA Sequence	ORF Start: at 10	ORF Stop: end of sequence
CGCGGATCCCAAACTCCAGTGCTCTCATCCAGAGGCTCTTGTGATTCTCTTTGCAATTGTGAGGAAAA
AGATGGCACAATGCTAATAAATTGTGAAGCAAAAGGTATCAAGATGGTATCTGAAATAAGTGTGCCAC
CATCACGACCTTTCCAACTAAGCTTATTAAATAACGGCTTGACGATGCTTCACACAAATGACTTTTCT
GGGCTTACCAATGCTATTTCAATACACCTTGGATTTAACAATATTGCAGATATTGAGATAGGTGCATT
TAATGGCCTTGGCCTCCTGAAACAACTTCATATCAATCACAATTCTTTAGAAATTCTTAAAGAGGATA
CTTTCCATGGACTGGAAAACCTGGAATTCCTGCAAGCAGATAACAATTTTATCACAGTGATTGAACCA
AGTGCCTTTAGCAAGCTCAACAGACTCAAAGTGTTAATTTTAAATGACAATGCTATTGAGAGTCTTCC
TCCAAACATCTTCCGATTTGTTCCTTTAACCCATCTAGATCTTCGTGGAAATCAATTACAAACATTGC
CTTATGTTGGTTTTCTCGAACACATTGGCCGAATATTGGATCTTCAGTTGGAGGACAACAAATGGGCC
TGCAATTGTGACTTATTGCAGTTAAAAACTTGGTTGGAGAACATGCCTCCACAGTCTATAATTGGTGA
TGTTGTCTGCAACAGCCCTCCATTTTTTAAAGGAAGTATACTCAGTAGACTAAAGAAGGAATCTATTT
GCCCTACTCCACCAGTGTATGAAGAACATGAGGATCCTTCAGGATCATTACATCTGGCAGCAACATCT
TCAATAAATGATAGTCGCATGTCAACTAAGACCACGTCCATTCTAAAACTACCCACCAAAGCACCAGG
TTTGATACCTTATATTACAAAGCCATCCACTCAACTTCCAGGACCTTACTGCCCTATTCCTTGTAACT
GCAAAGTCCTATCCCCATCAGGACTTCTAATACATTGTCAGGAGCGCAACATTGAAAGCTTATCAGAT
CTGAGACCTCCTCCGCAAAATCCTAGAAAGCTCATTCTAGCGGGAAATATTATTCACAGTTTAATGAA
GTCTGATCTAGTGGAATATTTCACTTTGGAAATGCTTCACTTGGGAAACAATCGTATTGAAGTTCTTG
AAGAAGGATCGTTTATGAACCTAACGAGATTACAAAAACTCTATCTAAATGGTAACCACCTGACCAAA
TTAAGTAAAGGCATGTTCCTTGGTCTCCATAATCTTGAATACTTATATCTTGAATACAATGCCATTAA
GCAAATACTGCCAGGAACCTTTAATCCAATGCCTAAACTTAAAGTCCTGTATTTAAATAACAACCTCC
TCCAAGTTTTACCACCACATATTTTTTCAGGGGTTCCTCTAACTAAGGTAAATCTTAAAACAAACCAG
TTTACCCATCTACCTGTAAGTAATATTTTGGATGATCTTGATTTACTAACCCAGATTGACCTTGAGGA
TAACCCCTGGGACTGCTCCTGTGACCTGGTTGGACTGCAGCAATGGATACAAAAGTTAAGCAAGAACA
CAGTGACAGATGACATCCTCTGCACTTCCCCCGGGCATCTCGACAAAAAGGAATTGAAAGCCCTAAAT
AGTGAAATTCTCTGTCCAGGTTTAGTAAATAACCCATCCATGCCAACACAGACTAGTTACCTTATGGT
CACCACTCCTGCAACAACAACAAATACGGCTGATACTATTTTACGATCTCTCGAGGCG
NOV6c, CG52997-03
Protein Sequence	SEQ ID NO: 78	580 aa	MW at 64615.9kD
QTPVLSSRGSCDSLCNCEEKDGTMLINCEAKGIKMVSEISVPPSRPFQLSLLNNGLTMLHTNDFSGLT
NAISIHLGFNNIADIEIGAFNGLGLLKQLHINHNSLEILKEDTFHGLENLEFLQADNNFITVIEPSAF
SKLNRLKVLILNDNAIESLPPNIFRFVPLTHLDLRGNQLQTLPYVGFLEHIGRILDLQLEDNKWACNC
DLLQLKTWLENMPPQSIIGDVVCNSPPFFKGSILSRLKKESICPTPPVYEEHEDPSGSLHLAATSSIN
DSRMSTKTTSILKLPTKAPGLIPYITKPSTQLPGPYCPIPCNCKVLSPSGLLIHCQERNIESLSDLRP
PPQNPRKLILAGNIIHSLMKSDLVEYFTLEMLHLGNNRIEVLEEGSFMNLTRLQKLYLNGNHLTKLSK
GMFLGLHNLEYLYLEYNAIKEILPGTFNPMPKLKVLYLNNNLLQVLPPHIFSGVPLTKVNLKTNQFTH
LPVSNILDDLDLLTQIDLEDNPWDCSCDLVGLQQWIQKLSKNTVTDDILCTSPGHLDKKELKALNSEI
LCPGLVNNPSMPTQTSYLMVTTPATTTNTADTILRS
NOV6d, CG52997-04	SEQ ID NO: 79	1762 bp
DNA Sequence	ORF Start: at 14	ORF Stop: end of sequence
CACCTCGCGAACCCAAACTCCAGTGCTCTCATCCAGAGGCTCTTGTGATTCTCTTTGCAATTGTGAGG
AAAAAGATGGCACAATGCTAATAAATTGTGAAGCAAAAGGTATCAAGATGGTATCTGAAATAAGTGTG
CCACCATCACGACCTTTCCAACTAAGCTTATTAAATAACGGCTTGACGATGCTTCACACAAATGACTT
TTCTGGGCTTACCAATGCTATTTCAATACACCTTGGATTTAACAATATTGCAGATATTGAGATAGGTG
CATTTAATGGCCTTGGCCTCCTGAAACAACTTCATATCAATCACAATTCTTTAGAAATTCTTAAAGAG
GATACTTTCCATGGACTGGAAAACCTGGAATTCCTGCAAGCAGATAACAATTTTATCACAGTGATTGA
ACCAAGTGCCTTTAGCAAGCTCAACAGACTCAAAGTGTTAATTTTAAATGACAATGCTATTGAGAGTC
TTCCTCCAAACATCTTCCGATTTGTTCCTTTAACCCATCTAGATCTTCGTGGAAATCAATTACAAACA
TTGCCTTATGTTGGTTTTCTCGAACACATTGGCCGAATATTGGATCTTCAGTTGGAGGACAACAAATG
GGCCTGCAATTGTGACTTATTGCAGTTAAAAACTTGGTTGGAGAACATGCCTCCACAGTCTATAATTG
GTGATGTTGTCTGCAACAGCCCTCCATTTTTTAAAGGAAGTATACTCAGTAGACTAAAGAAGGAATCT
ATTTGCCCTACTCCACCAGTGTATGAAGAACATGAGGATCCTTCAGGATCATTACATCTGGCAGCAAC
ATCTTCAATAAATGATAGTCGCATGTCAACTAAGACCACGTCCATTCTAAAACTACCCACCAAAGCAC
CAGGTTTGATACCTTATATTACAAAGCCATCCACTCAACTTCCAGGACCTTACTGCCCTATTCCTTGT
AACTGCAAAGTCCTATCCCCATCAGGACTTCTAATACATTGTCAGGAGCGCAACATTGAAAGCTTATC
AGATCTGAGACCTCCTCCGCAAAATCCTAGAAAGCTCATTCTAGCGGGAAATATTATTCACAGTTTAA
TGAAGTCTGATCTAGTGGAATATTTCACTTTGGAAATGCTTCACTTGGGAAACAATCGTATTGAAGTT
CTTGAAGAAGGATCGTTTATGAACCTAACGAGATTACAAAAACTCTATCTAAATGGTAACCACCTGAC
CAAATTAAGTAAAGGCATGTTCCTTGGTCTCCATAATCTTGAATACTTATATCTTGAATACAATGCCA
TTAAGGAAATACTGCCAGGAACCTTTAATCCAATGCCTAAACTTAAAGTCCTGTATTTAAATAACAAC
CTCCTCCAAGTTTTACCACCACATATTTTTTCAGGGGTTCCTCTAACTAAGGTAAATCTTAAAACAAA
CCAGTTTACCCATCTACCTGTAAGTAATATTTTGGATGATCTTCATTTACTAACCCAGATTGACCTTG
AGGATAACCCCTGGGACTGCTCCTGTGACCTGGTTGGACTGCAGCAATGGATACAAAAGTTAAGCAAG
AACACAGTGACAGATGACATCCTCTGCACTTCCCCCGGGCATCTCGACAAAAAGGAATTGAAAGCCCT
AAATAGTGAAATTCTCTGTCCAGGTTTAGTAAATAACCCATCCATGCCAACACAGACTAGTTACCTTA
TGGTCACCACTCCTGCAACAACAACAAATACGGCTGATACTATTTTACGATCTGTCGACGGC
NOV6d, CG52997-04
Protein Sequence	SEQ ID NO: 80	580 aa	MW at 64615.9kD
QTPVLSSRGSCDSLCNCEEKDGTMLINCEAKGIKMVSEISVPPSRPFQLSLLNNGLTMLHTNDFSGLT
NAISIHLGFNNIADIEIGAFNGLGLLKQLHINHNSLEILKEDTFHGLENLEFLQADNNFITVIEPSAF
SKLNRLKVLILNDNAIESLPPNIFRFVPLTHLDLRGNQLQTLPYVGFLEHIGRILDLQLEDNKWACNC
DLLQLKTWLENMPPQSIIGDVVCNSPPFFKGSILSRLKKESICPTPPVYEEHEDPSGSLHLAATSSIN
DSRMSTKTTSILKLPTKAPGLIPYITKPSTQLPGPYCPIPCNCKVLSPSGLLIHCQERNIESLSDLRP
PPQNPRKLILAGNIIHSLMKSDLVEYFTLEMLHLGNNRIEVLEEGSFMNLTRLQKLYLNGNHLTKLSK
GMFLGLHNLEYLYLEYNAIKEILPGTFNPMPKLKVLYLNNNLLQVLPPHIFSGVPLTKVNLKTNQFTH
LPVSNILDDLDLLTQIDLEDNPWDCSCDLVGLQQWIQKLSKNTVTDDILCTSPGHLDKKELKALNSEI
LCPGLVNNPSMPTQTSYLMVTTPATTTNTADTILRS
NOV6e, CG52997-05	SEQ ID NO: 81	2481 bp
DNA Sequence	ORF Start: at 10	ORF Stop: end of sequence
CGCGGATCCCAAACTCCAGTGCTCTCATCCAGAGGCTCTTGTGATTCTCTTTGCAATTGTGAGGAAAA
AGATGGCACAATGCTAATAAATTGTGAAGCAAAAGGTATCAAGATGGTATCTGAAATAAGTGTGCCAC
CATCACGACCTTTCCAACTAACCTTATTAAATAACGGCTTGACGATGCTTCACACAAATGACTTTTCT
GGGCTTACCAATGCTATTTCAATACACCTTGGATTTAACAATATTGCAGATATTGAGATAGGTGCATT
TAATGGCCTTGGCCTCCTGAAACAACTTCATATCAATCACAATTCTTTAGAAATTCTTAAAGAGGATA
CTTTCCATGGACTGGAAAACCTGGAATTCCTGCAAGCAGATAACAATTTTATCACAGTGATTGAACCA
AGTGCCTTTAGCAAGCTCAACAGACTCAAAGTGTTAATTTTAAATGACAATGCTATTGAGAGTCTTCC
TCCAAACATCTTCCGATTTGTTCCTTTAACCCATCTAGATCTTCGTGGAAATCAATTACAAACATTGC
CTTATGTTGGTTTTCTCGAACACATTGGCCGAATATTGGATCTTCAGTTGGAGGACAACAAATGGGCC
TGCAATTGTGACTTATTGCAGTTAAAAACTTGGTTGGAGAACATGCCTCCACAGTCTATAATTGGTGA
TGTTGTCTGCAACAGCCCTCCATTTTTTAAAGGAAGTATACTCAGTAGACTAAAGAAGGAATCTATTT
GCCCTACTCCACCAGTGTATGAAGAACATGAGGATCCTTCAGGATCATTACATCTGGCAGCAACATCT
TCAATAAATGATAGTCGCATGTCAACTAAGACCACGTCCATTCTAAAACTACCCACCAAAGCACCAGG
TTTGATACCTTATATTACAAAGCCATCCACTCAACTTCCAGGACCTTACTGCCCTATTCCTTGTAACT
GCAAAGTCCTATCCCCATCAGGACTTCTAATACATTGTCAGGAGCGCAACATTGAAAGCTTATCAGAT
CTGAGACCTCCTCCGCAAAATCCTAGAAAGCTCATTCTAGCGGGAAATATTATTCACAGTTTAATGAA
GTCTGATCTAGTGGAATATTTCACTTTGGAAATGCTTCACTTGGGAAACAATCGTATTGAAGTTCTTG
AAGAAGGATCGTTTATGAACCTAACGAGATTACAAAAACTCTATCTAAATGGTAACCACCTGACCAAA
TTAAGTAAAGGCATGTTCCTTGGTCTCCATAATCTTGAATACTTATATCTTGAATACAATGCCATTAA
GGAAATACTGCCAGGAACCTTTAATCCAATGCCTAAACTTAAAGTCCTGTATTTAAATAACAACCTCC
TCCAAGTTTTACCACCACATATTTTTTCAGGGGTTCCTCTAACTAAGGTAAATCTTAAAACAAACCAG
TTTACCCATCTACCTGTAAGTAATATTTTGGATGATCTTGATTTACTAACCCAGATTGACCTTGAGGA
TAACCCCTGGGACTGCTCCTGTGACCTGGTTGGACTGCAGCAATGGATACAAAAGTTAAGCAAGAACA
CAGTGACAGATGACATCCTCTGCACTTCCCCCGGCCATCTCGACAAAAAGGAATTGAAAGCCCTAAAT
AGTGAAATTCTCTGTCCAGGTTTAGTAAATAACCCATCCATGCCAACACAGACTAGTTACCTTATGGT
CACCACTCCTGCAACAACAACAAATACGGCTGATACTATTTTACGATCTCTTACGGACGCTGTGCCAC
TGTCTGTTCTAATATTGGGACTTCTGATTATGTTCATCACTATTGTTTTCTGTGCTGCAGGGATAGTG
GTTCTTGTTCTTCACCGCAGGAGAAGATACAAAAAGAAACAAGTAGATGAGCAAATGAGAGACAACAG
TCCTGTGCATCTTCAGTACAGCATGTATGGCCATAAAACCACTCATCACACTACTGAAAGACCCTCTG
CCTCACTCTATGAACAGCACATGGTGAGCCCCATGGTTCATGTCTATAGAAGTCCATCCTTTGGTCCA
AAGCATCTGGAAGAGGAAGAAGAGAGGAATGAGAAAGAAGGAAGTGATGCAAAACATCTCCAAAGAAG
TCTTTTGGAACAGGAAAATCATTCACCACTCACAGGGTCAAATATGAAATACAAAACCACGAACCAAT
CAACAGAATTTTTATCCTTCCAAGATGCCAGCTCATTGTACAGAAACATTTTAGAAAAAGAAAGGGAA
CTTCAGCAACTGGGAATCACAGAATACCTAAGGAAAAACATTGCTCAGCTCCAGCCTGATATGGAGGC
ACATTATCCTGGAGCCCACGAAGAGCTGAAGTTAATGGAAACATTAATGTACTCACGTCCAAGGAAGG
TATTAGTGGAACAGACAAAAAATGAGTATTTTGAACTTAAAGCTAATTTACATGCTGAACCTGACTAT
TTAGAAGTCCTGGAGCAGCAAACACTCGAGGCG
NOV6e, CG52997-05
Protein Sequence	SEQ ID NO: 82	821 aa	MW at 92763.6kD
QTPVLSSRGSCDSLCNCEEKDGTMLINCEAKGIKMVSEISVPPSRPFQLSLLNNGLTMLHTNDFSGLT
NAISIHLGFNNIADIEIGAFNGLGLLKQLHINHNSLEILKEDTFHGLENLEFLQADNNFITVIEPSAF
SKLNRLKVLILNDNAIESLPPNIFRFVPLTHLDLRGNQLQTLPYVGFLEHIGRILDLQLEDNKWACNC
DLLQLKTWLENMPPQSIIGDVVCNSPPFFKGSILSRLKKESICPTPPVYEEHEDPSGSLHLAATSSIN
DSRMSTKTTSILKLPTKAPGLIPYITKPSTQLPGPYCPIPCNCKVLSPSGLLIHCQERNIESLSDLRP
PPQNPRKLILAGNIIHSLMKSDLVEYFTLEMLHLGNNRIEVLEEGSFMNLTRLQKLYLNGNHLTKLSK
GMFLGLHNLEYLYLEYNAIKEILPGTFNPMPKLKVLYLNNNLLQVLPPHIFSGVPLTKVNLKTNQFTH
LPVSNILDDLDLLTQIDLEDNPWDCSCDLVGLQQWIQKLSKNTVTDDILCTSPGHLDKKELKALNSEI
LCPGLVNNPSMPTQTSYLMVTTPATTTNTADTILRSLTDAVPLSVLILGLLIMFITIVFCAAGIVVLV
LHRRRRYKKKQVDEQMRDNSPVHLQYSMYGHKTTHHTTERPSASLYEQHMVSPMVHVYRSPSFGPKHL
EEEEERNEKEGSDAKHLQRSLLEQENHSPLTGSNMKYKTTNQSTEFLSFQDASSLYRNILEKERELQQ
LGITEYLRKNIAQLQPDMEAHYPGAHEELKLMETLMYSRPRKVLVEQTKNEYFELKANLHAEPDYLEV
LEQQT

[0409] The NOV6f 13375304 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 6B.

TABLE 6B
NOV6f Sequence Analysis
NOV6f, 13375304	SEQ ID NO: 83	2838 bp
DNA Sequence	ORF Start: ATG at 184	ORF Stop: end of sequence
AACTTTATGAAGCTATGGGACTTGACAAAAAGTGATATTTGAGAAGAAAGTACGCAGTGGTTGGTGTT
TTCTTTTTTTTAATAAAGGAATTGAATTACTTTGAACACCTCTTCCAGCTGTGCATTACAGATAACGT
CAGGAAGAGTCTCTGCTTTACAGAATCGGATTTCATCACATGACAACATGAAGCTGTGGATTCATCTC
TTTTATTCATCTCTCCTTGCCTGTATATCTTTACACTCCCAAACTCCAGTGCTCTCATCCAGAGGCTC
TTGTGATTCTCTTTGCAATTGTGAGGAAAAAGATGGCACAATGCTAATAAATTGTGAAGCAAAAGGTA
TCAAGATGGTATCTGAAATAAGTGTGCCACCATCACGACCTTTCCAACTAAGCTTATTAAATAACGGC
TTGACGATGCTTCACACAAATGACTTTTCTGGGCTTACCAATGCTATTTCAATACACCTTGGATTTAA
CAATATTGCAGATATTGAGATAGGTGCATTTAATGGCCTTGGCCTCCTGAAACAACTTCATATCAATC
ACAATTCTTTAGAAATTCTTAAAGAGGATACTTTCCATGGACTGGAAAACCTGGAATTCCTGCAAGCA
GATAACAATTTTATCACAGTGATTGAACCAAGTGCCTTTAGCAAGCTCAACAGACTCAAAGTGTTAAT
TTTAAATGACAATGCTATTGAGAGTCTTCCTCCAAACATCTTCCGATTTGTTCCTTTAACCCATCTAG
ATCTTCGTGGAAATCAATTACAAACATTGCCTTATGTTGGTTTTCTCGAACACATTGGCCGAATATTG
GATCTTCAGTTGGAGGACAACAAATGGGCCTGCAATTGTGACTTATTGCAGTTAAAAACTTGGTTGGA
GAACATGCCTCCACAGTCTATAATTGGTGATGTTGTCTGCAACAGCCCTCCATTTTTTAAAGGAAGTA
TACTCAGTAGACTAAAGAAGGAATCTATTTGCCCTACTCCACTAGTGTATGAAGAACATGAGGATCCT
TCAGGATCATTACATCTGGCAGCAACATCTTCAATAAATGATAGTCGCATGTCAACTAAGACCACGTC
CATTCTAAAACTACCCACCAAAGCACCAGGTTTGATACCTTATATTACAAAGCCATCCACTCAACTTC
CAGGACCTTACTGCCCTATTCCTTGTAACTGCAAAGTCCTATCCCCATCAGGACTTCTAATACATTGT
CAGGAGCGCAACATTGAAAGCTTATCAGATCTGAGACCTCCTCCGCAAAATCCTAGAAAGCTCATTCT
AGCGGGAAATATTATTCACAGTTTAATGAAGTCTGATCTAGTCGAATATTTCACTTTGGAAATGCTTC
ACTTGGGAAACAATCGTATTGAAGTTCTTGAAGAAGGATCGTTTATGAACCTAACGAGATTACAAAAA
CTCTATCTAAATGGTAACCACCTGACCAAATTAAGTAAAGGCATGTTCCTTGGTCTCCATAATCTTGA
ATACTTATATCTTGAATACAATGCCATTAAGGAAATACTGCCAGGAACCTTTAATCCAATGCCTAAAC
TTAAAGTCCTGTATTTAAATAACAACCTCCTCCAAGTTTTACCACCACATATTTTTTCAGGGGTTCCT
CTAACTAAGGTAAATCTTAAAACAAACCAGTTTACCCATCTACCTGTAAGTAATATTTTGGATGATCT
TGATTTACTAACCCAGATTGACCTTCAGGATAACCCCTGGGACTGCTCCTGTGACCTGGTTGGACTGC
AGCAATGGATACAAAAGTTAAGCAAGAACACAGTGACAGATGACATCCTCTGCACTTCCCCCGGGCAT
CTCGACAAAAAGGAATTGAAAGCCCTAAATAGTGAAATTCTCTGTCCAGGTTTAGTAAATAACCCATC
CATGCCAACACAGACTAGTTACCTTATGGTCACCACTCCTGCAACAACAACAAATACGGCTGATACTA
TTTTACGATCTCTTACGGACGCTGTGCCACTGTCTGTTCTAATATTGGGACTTCTGATTATGTTCATC
ACTATTGTTTTCTGTGCTGCAGGGATAGTGGTTCTTGTTCTTCACCGCAGGAGAAGATACAAAAAGAA
ACAAGTAGATGAGCAAATGAGAGACAACAGTCCTGTGCATCTTCAGTACAGCATGTATGGCCATAAAA
CCACTCATCACACTACTGAAAGACCCTCTGCCTCACTCTATGAACAGCACATCGTGAGCCCCATGGTT
CATGTCTATAGAAGTCCATCCTTTGGTCCAAAGCATCTGGAAGAGGAAGAAGAGAGGAATGAGAAAGA
AGGAAGTGATGCAAAACATCTCCAAAGAAGTCTTTTGGAACAGGAAAATCATTCACCACTCACAGGGT
CAAATATGAAATACAAAACCACGAACCAATCAACAGAATTTTTATCCTTCCAAGATGCCAGCTCATTG
TACAGAAACATTTTAGAAAAAGAAAGGGAACTTCAGCAACTGGGAATCACAGAATACCTAAGGAAAAA
CATTGCTCAGCTCCAGCCTGATATGGAGGCACATTATCCTGGAGCCCACGAAGAGCTGAAGTTAATGG
AAACATTAATGTACTCACGTCCAAGGAAGGTATTAGTGGAACAGACAAAAAATGAGTATTTTGAACTT
AAAGCTAATTTACATGCTGAACCTGACTATTTAGAACTCCTGGAGCAGCAAACATAGATGGAGAGTTT
GAGGGCTTTCGCAGAAATGCTGTGATTCTGTTTTAAGTCCATACCTTGTAAATTAGTGCCTTACGTGA
GTGTGTCATCCATCAGAACCTAAGCACAGCAGTAAACTATGGAGAAAAAA
NOV6f, 13375304
Protein Sequence	SEQ ID NO: 84	841 aa	MW at 95108.5kD
MKLWIHLFYSSLLACISLHSQTPVLSSRGSCDSLCNCEEKDGTMLINCEAKGIKMVSEISVPPSRPFQ
LSLLNNGLTMLHTNDFSGLTNAISIHLGFNNIADIEIGAFNGLGLLKQLHINHNSLEILKEDTFHGLE
NLEFLQADNNFITVIEPSAFSKLNRLKVLILNDNAIESLPPNIFRFVPLTHLDLRGNQLQTLPYVGFL
EHIGRILDLQLEDNKWACNCDLLQLKTWLENMPPQSIIGDVVCNSPPFFKGSILSRLKKESICPTPSV
YEEHEDPSGSLHLAATSSINDSRMSTKTTSILKLPTKAPGLIPYITKPSTQLPGPYCPIPCNCKVLSP
SGLLIHCQERNIESLSDLRPPPQNPRKLILAGNIIHSLMKSDLVEYFTLEMLHLGNNRIEVLEEGSFM
NLTRLQKLYLNGNHLTKLSKGMFLGLHNLEYLYLEYNAIKEILPGTFNPMPKLKVLYLNNNLLQVLPP
HIFSGVPLTKVNLKTNQFTHLPVSNILDDLDLLTQIDLEDNPWDCSCDLVGLQQWIQKLSKNTVTDDI
LCTSPGHLDKKELKALNSEILCPGLVNNPSMPTQTSYLMVTTPATTTNTADTILRSLTDAVPLSVLIL
GLLIMFITIVFCAAGIVVLVLHRRRRYKKKQVDEQMRDNSPVHLQYSMYGHKTTHHTTERPSASLYEQ
HMVSPMVHVYRSPSFGPKHLEEEEERNEKEGSDAKHLQRSLLEQENHSPLTGSNMKYKTTNQSTEFLS
FQDASSLYRNILEKERELQQLGITEYLRKNIAQLQPDMEAHYPGAHEELKLMETLMYSRPRKVLVEQT
KNEYFELKANLHAEPDYLEVLEQQT

[0410] The NOV 6g 13376158 clone was analyzed, and the nucleotide and encoded polypeptide 5 sequences are shown in Table 6C.

TABLE 6C
NOV6 Sequence Analysis
NOV6g, 13376158	SEQ ID NO: 85	2838 bp
DNA Sequence	ORF Start: ATG at 184	ORF Stop: end of sequence
AACTTTATGAAGCTATGGGACTTGACAAAAAGTGATATTTGAGAAGAAAGTACGCAGTGGTTGGTGTT
TTCTTTTTTTTAATAAAGGAATTGAATTACTTTGAACACCTCTTCCAGCTGTGCATTACACATAACGT
CAGGAAGAGTCTCTGCTTTACAGAATCGGATTTCATCACATGACAACATGAAGCTGTGGATTCATCTC
TTTTATTCATCTCTCCTTGCCTGTATATCTTTACACTCCCAAACTCCAGTGCTCTCATCCAGAGGCTC
TTGTGATTCTCTTTGCAATTGTGAGGAAAAAGATGGCACAATGCTAATAAATTGTGAAGCAAAAGGTA
TCAAGATGGTATCTGAAATAAGTGTGCCACCATCACGACCTTTCCAACTAAGCTTATTAAATAACGGC
TTGACGATGCTTCACACAAATGACTTTTCTGGGCTTACCAATGCTATTTCAATACACCTTGGATTTAA
CAATATTGCAGATATTGAGATAGGTGCATTTAATGGCCTTGGCCTCCTGAAACAACTTCATATCAATC
ACAATTCTTTAGAAATTCTTAAAGACGATACTTTCCATGGACTGGAAAACCTGGAATTCCTGCAAGCA
GATAACAATTTTATCACAGTGATTGAACCAAGTGCCTTTAGCAAGCTCAACAGACTCAAAGTGTTAAT
TTTAAATGACAATGCTATTGAGAGTCTTCCTCCAAACATCTTCCGATTTGTTCCTTTAACCCATCTAG
ATCTTCGTGGAAATCAATTACAAACATTGCCTTATGTTGGTTTTCTCGAACACATTGGCCGAATATTG
GATCTTCAGTTGGAGGACAACAAATGGGCCTGCAATTGTGACTTATTGCAGTTAAAAACTTGGTTGGA
GAACATGCCTCCACAGTCTATAATTGGTGATGTTGTCTGCAACAGCCCTCCATTTTTTAAAGGAAGTA
TACTCAGTAGACTAAAGAAGGAATCTATTTGCCCTACTCCACCAGTGTATGAAGAACATGAGGATCCT
TCAGGATCATTACATCTGGCAGCAACATCTTCAATAAATGATAGTCGCATGTCAACTAAGACCACGTC
CATTCTAAAACTACCCACCAAAGCACCAGGTTTGATACCTTATATTACAAAGCCATCCACTCAACTTC
CAGGACCTTACTGCCCTATTCCTTGTAACTGCAAAGTCCTATCCCCATCAGGACTTCTAATACATTGT
CAGCAGCGCAACATTGAAAGCTTATCAGATCTGAGACCTCCTCCGCAAAATCCTAGAAAGCTCATTCT
AGCGGGAAATATTATTCACAGTTTAATGAAGTCTGATCTAGTGGAATATTTCACTTTGGAAATGCTTC
ACTTGGGAAACAATCGTATTGAAGTTCTTGAAGAAGGATCGTTTATGAACCTAACGAGATTACAGAAA
CTCTATCTAAATGGTAACCACCTGACCAAATTAAGTAAAGGCATGTTCCTTGGTCTCCATAATCTTGA
ATACTTATATCTTGAATACAATGCCATTAAGGAAATACTGCCAGGAACCTTTAATCCAATGCCTAAAC
TTAAAGTCCTGTATTTAAATAACAACCTCCTCCAAGTTTTACCACCACATATTTTTTCAGGGGTTCCT
CTAACTAAGGTAAATCTTAAAACAAACCAGTTTACCCATCTACCTGTAAGTAATATTTTGGATGATCT
TGATTTACTAACCCAGATTGACCTTGAGGATAACCCCTGGGACTGCTCCTGTGACCTGGTTGGACTGC
AGCAATGGATACAAAAGTTAAGCAAGAACACAGTGACAGATGACATCCTCTGCACTTCCCCCGGGCAT
CTCGACAAAAAGGAATTGAAAGCCCTAAATAGTGAAATTCTCTGTCCAGGTTTAGTAAATAACCCATC
CATGCCAACACAGACTAGTTACCTTATGGTCACCACTCCTGCAACAACAACAAATACGGCTGATACTA
TTTTACGATCTCTTACGGACGCTGTGCCACTGTCTGTTCTAATATTGGGACTTCTGATTATGTTCATC
ACTATTGTTTTCTGTGCTGCAGGGATAGTGGTTCTTGTTCTTCACCGCAGGAGAAGATACAAAAAGAA
ACAAGTAGATGAGCAAATGAGAGACAACAGTCCTGTGCATCTTCAGTACAGCATGTATGGCCATAAAA
CCACTCATCACACTACTGAAAGACCCTCTGCCTCACTCTATGAACAGCACATGGTGAGCCCCATGGTT
CATGTCTATAGAAGTCCATCCTTTGGTCCAAAGCATCTGGAAGAGGAAGAAGAGAGGAATGAGAAAGA
AGGAAGTGATGCAAAACATCTCCAAAGAAGTCTTTTGGAACAGGAAAATCATTCACCACTCACAGGGT
CAAATATGAAATACAAAACCACGAACCAATCAACAGAATTTTTATCCTTCCAAGATGCCAGCTCATTG
TACAGAAACATTTTAGAAAAAGAAAGGGAACTTCAGCAACTGGGAATCACAGAATACCTAAGGAAAAA
CATTGCTCAGCTCCAGCCTGATATGGAGGCACATTATCCTGGAGCCCACGAAGAGCTGAAGTTAATGG
AAACATTAATGTACTCACGTCCAAGGAAGGTATTAGTGGAACAGACAAAAAATGAGTATTTTGAACTT
AAAGCTAATTTACATGCTGAACCTGACTATTTAGAAGTCCTGGAGCAGCAAACATAGATGGAGAGTTT
GAGGGCTTTCGCAGAAATGCTGTGATTCTGTTTTAAGTCCATACCTTGTAAATTAGTGCCTTACGTGA
GTGTGTCATCCATCAGAACCTAAGCACAGCAGTAAACTATGGAGAAAAAA
NOV6g, 13376158
Protein Sequence	SEQ ID NO: 86	841 aa	MW at 95108.5kD
MKLWIHLFYSSLLACISLHSQTPVLSSRGSCDSLCNCEEKDGTMLINCEAKGIKMWSEISVPPSRPFQ
LSLLNNGLTMLHTNDFSGLTNAISIHLGFNNIADIEIGAFNGLGLLKQLHINHNSLEILKEDTFHGLE
NLEFLQADNNFITVIEPSAFSKLNRLKVLILNDNAIESLPPNIFRFVPLTHLDLRGNQLQTLPYVGFL
EHIGRILDLQLEDNKWACNCDLLQLKTWLENMPPQSIIGDVVCNSPPFFKGSILSRLKKESICPTPPV
YEEHEDPSGSLHLAATSSINDSRMSTKTTSILKLPTKAPGLIPYITKPSTQLPGPYCPIPCNCKVLSP
SGLLIHCQERNIESLSDLRPPPQNPRKLILAGNIIHSLMKSDLVEYFTLEMLHLGNNRIEVLEEGSFM
NLTRLRKLYLNGNHLTKLSKGMFLGLHNLEYLYLEYNAIKEILPGTFNPMPKLKVLYLNNNLLQVLPP
HIFSGVPLTKVNLKTNQFTHLPVSNILDDLDLLTQIDLEDNPWDCSCDLVGLQQWIQKLSKNTVTDDI
LCTSPGHLDKKELKALNSEILCPGLVNNPSMPTQTSYLMVTTPATTTNTADTILRSLTDAVPLSVLIL
GLLIMFITIVFCAAGIVVLVLHRRRRYKKKQVDEQMRDNSPVHLQYSMYGHKTTHHTTERPSASLYEQ
HMVSPMVHVYRSPSFGPKHLEEEEERNEKEGSDAKHLQRSLLEQENHSPLTGSNMKYKTTNQSTEFLS
FQDASSLYRNILEKERELQQLGITEYLRKNIAQLQPDMEAHYPGAHEELKLMETLMYSRPRKVLVEQT
KNEYFELKANLHAEPDYLEVLEQQT

[0411] A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 6D.

TABLE 6D
Comparison of the NOV6 protein sequences.
NOV6a MKLWIHLFYSSLLACISLHSQTPVLSSRGSCDSLCNCEEKDGTMLINCEAKGIKMVSEIS
NOV6b ----DSLFYSSLLACISLHSQTPVLSSRGSCDSLCNCEEKDGTMLINCEAKGIKMVSEIS
NOV6c --------------------QTPVLSSRGSCDSLCNCEEKDGTMLINCEAKGIKMVSEIS
NOV6d --------------------QTPVLSSRGSCDSLCNCEEKDGTMLINCEAKGIKMVSEIS
NOV6e --------------------QTPVLSSRGSCDSLCNCEEKDGTMLINCEAKGIKMVSEIS
NOV6a VPPSRPFQLSLLNNGLTMLHTNDFSGLTNAISIHLGFNNIADIEIGAFNGLGLLKQLHIN
NOV6b VLPSRPFQLSLLNNGLTMLHTNDFSGLTNAISIHLGFNNIADIEIGAFNGLGLLKQLHIN
NOV6c VPPSRPFQLSLLNNGLTMLHTNDFSGLTNAISIHLGFNNIADIEIGAFNGLGLLKQLHIN
NOV6d VPPSRPFQLSLLNNGLTMLHTNDFSGLTNAISIHLGFNNIADIEIGAFNGLGLLKQLHIN
NOV6e VPPSRPFQLSLLNNGLTMLHTNDFSGLTNAISIHLGFNNIADIEIGAFNGLGLLKQLHIN
NOV6a HNSLEILKEDTFHGLENLEFLQADNNFITVIEPSAFSKLNRLKVLILNDNAIESLPPNIF
NOV6b HNSLEILKEDTFHGLENLEFLQADNNFITVIEPSAFSKLNRLKVLILNDNAIESLPPNIF
NOV6c HNSLEILKEDTFHGLENLEFLQADNNFITVIEPSAFSKLNRLKVLILNDNAIESLPPNIF
NOV6d HNSLEILKEDTFHGLENLEFLQADNNFITVIEPSAFSKLNRLKVLILNDNAIESLPPNIF
NOV6e HNSLEILKEDTFHGLENLEFLQADNNFITVIEPSAFSKLNRLKVLILNDNAIESLPPNIF
NOV6a RFVPLTHLDLRGNQLQTLPYVGFLEHIGRILDLQLEDNKWACNCDLLQLKTWLENMPPQS
NOV6b RFVPLTHLDLRGNQLQTLPYVGFLEHIGRILDLQLEDNKWACNCDLLQLKTWLENMPPQS
NOV6c RFVPLTHLDLRGNQLQTLPYVGFLEHIGRILDLQLEDNKWACNCDLLQLKTWLENMPPQS
NOV6d RFVPLTHLDLRGNQLQTLPYVGFLEHIGRILDLQLEDNKWACNCDLLQLKTWLENMPPQS
NOV6e RFVPLTHLDLRGNQLQTLPYVGFLEHIGRILDLQLEDNKWACNCDLLQLKTWLENMPPQS
NOV6a IIGDVVCNSPPFFKGSILSRLKKESICPTPPVYEEHEDPSGSLHLAATSSINDSRMSTKT
NOV6b IIGDVVCNSPPFFKGSILSRLKKESICPTPPVYEEHEDPSGSLHLAATSSINDSRMSTKT
NOV6c IIGDVVCNSPPFFKGSILSRLKKESICPTPPVYEEHEDPSGSLHLAATSSTNDSRMSTKT
NOV6d IIGDVVCNSPPFFKGSILSRLKKESICPTPPVYEEHEDPSGSLHLAATSSINDSRMSTKT
NOV6e IIGDVVCNSPPFFKGSILSRLKKESICPTPPVYEEHEDPSGSLHLAATSSINDSRMSTKT
NOV6a TSILKLPTKAPGLIPYITKPSTQLPGPYCPIPCNCKVLSPSGLLIHCQERNIESLSDLRP
NOV6b TSILKLPTKAPGLIPYITKPSTQLPGPYCPIPCNCKVLSPSGLLIHCQERNIESLSDLRP
NOV6c TSILKLPTKAPGLIPYITKPSTQLPGPYCPIPCNCKVLSPSGLLIHCQERNIESLSDLRP
NOV6d TSILKLPTKAPGLIPYITKPSTQLPGPYCPIPCNCKVLSPSGLLIHCQERNIESLSDLRP
NOV6e TSILKLPTKAPGLIPYITKPSTQLPGPYCPIPCNCKVLSPSGLLIHCQERNIESLSDLRP
NOV6a PPQNPRKLILAGNIIHSLMKSDLVEYFTLEMLHLGNNRIEVLEEGSFMNLTRLQKLYLNG
NOV6b PPQNPRKLILAGNIIHSLMKSDLVEYFTLEMLHLGNNRIEVLEEGSFMNLTRLQKLYLNG
NOV6c PPQNPRKLILAGNIIHSLMKSDLVEYFTLEMLHLGNNRIEVLEEGSFMNLTRLQKLYLNG
NOV6d PPQNPRKLILAGNIIHSLMKSDLVEYFTLEMLHLGNNRIEVLEEGSFMNLTRLQKLYLNG
NOV6e PPQNPRKLILAGNIIHSLMKSDLVEYFTLEMLHLGNNRIEVLEEGSFMNLTRLQKLYLNG
NOV6a NHLTKLSKGMFLGLHNLEYLYLEYNAIKEILPGTFNPMPKLKVLYLNNNLLQVLPPHIFS
NOV6b NHLTKLSKGMFLGLHNLEYLYLEYNAIKEILPGTFNPMPKLKVLYLNNNLLQVLPPHIFS
NOV6c NHLTKLSKGMFLGLHNLEYLYLEYNAIKEILPGTFNPMPKLKVLYLNNNLLQVLPPHIFS
NOV6d NHLTKLSKGMFLGLHNLEYLYLEYNAIKEILPGTFNPMPKLKVLYLNNNLLQVLPPHIFS
NOV6e NHLTKLSKGMFLGLHNLEYLYLEYNAIKEILPGTFNPMPKLKVLYLNNNLLQVLPPHIFS
NOV6a GVPLTKVNLKTNQFTHLPVSNILDDLDLLTQIDLEDNPWDCSCDLVGLQQWIQKLSKNTV
NOV6b GVPLTKVNLKTNQFTHLPVSNILDDLDLLTQIDLEDNPWDCSCDLVGLQQWIQKLSKNTV
NOV6c GVPLTKVNLKTNQFTHLPVSNILDDLDLLTQIDLEDNPWDCSCDLVGLQQWIQKLSKNTV
NOV6d GVPLTKVNLKTNQFTHLPVSNILDDLDLLTQIDLEDNPWDCSCDLVGLQQWIQKLSKNTV
NOV6e GVPLTKVNLKTNQFTHLPVSNILDDLDLLTQIDLEDNPWDCSCDLVGLQQWIQKLSKNTV
NOV6a TDDILCTSPGHLDKKELKALNSEILCPGLVNNPSMPTQTSYLMVTTPATTTNTADTILRS
NOV6b TDDILCTSPGHLDKKELKALNSEILCPGLVNNPSMPTQTSYLMVTTPATTTNTADTILRS
NOV6c TDDILCTSPGHLDKKELKALNSEILCPGLVNNPSMPTQTSYLMVTTPATTTNTADTILRS
NOV6d TDDILCTSPGHLDKKELKALNSEILCPGLVNNPSMPTQTSYLMVTTPATTTNTADTILRS
NOV6e TDDILCTSPGHLDKKELKALNSEILCPGLVNNPSMPTQTSYLMVTTPATTTNTADTILRS
NOV6a LTDAVPLSVLILGLLIMFITIVFCAAGIVVLVLHRRRRYKKKQVDEQMRDNSPVHLQYSM
NOV6b LTDAVPLSVLILGLLIMFITIVFCAAGIVVLVLHRRRRYKKKQVDEQMRDNSPVHLQYSM
NOV6c ------------------------------------------------------------
NOV6d ------------------------------------------------------------
NOV6e LTDAVPLSVLILGLLIMFITIVFCAAGIVVLVLHRRRRYKKKQVDEQMRDNSPVHLQYSM
NOV6a YGHKTTHHTTERPSASLYEQHMVSPMVHVYRSPSFGPKHLEEEEERNEKEGSDAKHLQRS
NOV6b YGHKTTHHTTERPSASLYEQHMVSPMVHVYRSPSFGPKHLEEEEERNEKEGSDAKHLQRS
NOV6c ------------------------------------------------------------
NOV6d ------------------------------------------------------------
NOV6e YGHKTTHHTTERPSASLYEQHMVSPMVHVYRSPSFGPKHLEEEEERNEKEGSDAKHLQRS
NOV6a LLEQENHSPLTGSNMKYKTTNQSTEFLSFQDASSLYRNILEKERELQQLGITEYLRKNIA
NOV6b LLEQENHSPLTGSNMKYKTTNQSTEFLSFQDASSLYRNILEKERELQQLGITEYLRKNIA
NOV6c ------------------------------------------------------------
NOV6d ------------------------------------------------------------
NOV6e LLEQENHSPLTGSNMKYKTTNQSTEFLSFQDASSLYRNILEKERELQQLGITEYLRKNIA
NOV6a QLQPDMEAHYPGAHEELKLMETLMYSRPRKVLVEQTKNEYFELKANLHAEPDYLEVLEQQ
NOV6b QLQPDMEAHYPGAHEELKLMETLMYSRPRKVLVEQTKNEYFELKANLHAEPDYLEVLEQQ
NOV6c ------------------------------------------------------------
NOV6d ------------------------------------------------------------
NOV6e QLQPDMEAHYPGAHEELKLMETLMYSRPRKVLVEQTKNEYFELKANLHAEPDYLEVLEQQ
NOV6a T
NOV6b T
NOV6c -
NOV6d -
NOV6e T
NOV6a (SEQ ID NO:74)
NOV6b (SEQ ID NO:76)
NOV6c (SEQ ID NO:78)
NOV6d (SEQ ID NO:80)
NOV6e (SEQ ID NO:82)

[0412] Further analysis of the NOV6a protein yielded the following properties shown in Table 6E.

TABLE 6E
Protein Sequence Properties NOV6a
SignalP analysis:	Cleavage site between residues 21 and 22
PSORT II analysis:
PSG:	a new signal peptide prediction method
	N-region: length 2; pos.chg 1; neg.chg 0
	H-region: length 25; peak value  8.53
	PSG score:  4.13
GvH:	von Heijne's method for signal seq. recognition
	GvH score (threshold: −2.1): −3.75
	possible cleavage site: between 15 and 16
>>> 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 = −13.48 Transmembrane 609-625
	PERIPHERAL Likelihood = 1.48 (at 3)
	ALOM score: −13.48 (number of TMSs: 1)
MTOP:	Prediction of membrane topology (Hartmann et al.)
	Center position for calculation: 616
	Charge difference: 6.5  C(5.5) − N(−1.0)
	C > N: C-terminal side will be inside
>>>Caution: Inconsistent mtop result with signal peptide
>>> membrane topology: type 1b (cytoplasmic tail 609 to 841)
MITDISC: discrimination of mitochondrial targeting seq
	R content:	1	Hyd Moment(75):	5.82
	Hyd Moment(95):	9.48	G content:	1
	D/E content:	1	S/T content:	8
	Score: −1.79
Gavel: prediction of cleavage sites for mitochondrial preseq
	R-2 motif at 38 SRG|SC
NUCDISC: discrimination of nuclear localization signals
	pat4: HRRR (3) at 634
	pat4: RRRR (5) at 635
	pat4: RPRK (4) at 807
	pat7: none
	bipartite: none
	content of basic residues:  9.0%
	NLS Score: 0.28
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
	KLYLNGNHL at 415
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 614
	LL at 721
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
697	K	0.97
698	H	0.98
699	L	0.98
700	E	0.98
701	E	0.98
702	E	0.98
703	E	0.98
704	E	0.98
705	R	0.98
706	N	0.98
707	E	0.98
708	K	0.98
709	E	0.98
710	G	0.98
711	S	0.98
712	D	0.98
713	A	0.98
714	K	0.98
715	H	0.98
716	L	0.98
717	Q	0.98
718	R	0.98
719	S	0.98
720	L	0.98
721	L	0.98
722	E	0.98
723	Q	0.98
724	E	0.98
725	N	0.98
726	H	0.98
727	S	0.83
total: 31 residues
Final Results (k = 9/23):
73.9%: nuclear
8.7%: mitochondrial
4.3%: plasma membrane
4.3%: vesicles of secretory system
4.3%: cytoplasmic
4.3%: endoplasmic reticulum
>> prediction for CG52997-01 is nuc (k = 23)

[0413] PFam analysis predicts that the NOV6a protein contains the domains shown in the Table 6F.

TABLE 6F
Domain Analysis of NOV6a
	NOV6a	Identities/
	Match	Similarities
Pfam Domain	Region	for the Matched Region	Expect Value
LRR	137 . . . 160	10/25 (40%)	0.13
		19/25 (76%)
LRRCT	218 . . . 268	17/54 (31%)	2.6e−08
		39/54 (72%)
LRR	388 . . . 411	8/25 (32%)	0.05
		20/25 (80%)
LRR	412 . . . 435	11/25 (44%)	0.046
		21/25 (84%)
LRR	436 . . . 459	7/25 (28%)	0.04
		20/25 (80%)
LRR	460 . . . 483	11/25 (44%)	0.0043
		21/25 (84%)
LRRCT	517 . . . 567	17/54 (31%)	8.8e−08
		37/54 (69%)

Example 7. NOV 7, CG55690: FZD-9.

[0414] The NOV7 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 7A.

TABLE 7A
NOV7 Sequence Analysis
NOV7a, CG55690-01	SEQ ID NO: 87	2184 bp
DNA Sequence	ORF Start: ATG at 26	ORF Stop: end of sequence
CCGCCTTCGGCCCGGGCCTCCCGGGATGGCCGTGGCGCCTCTGCGGGGGGCGCTGCTGCTGTGGCAGC
TGCTGGCGGCGGGCGGCGCGGCACTGGAGATCGGCCGCTTCGACCCGGAGCGCGGGCGCGGGGCTGCG
CCGTGCCAGGCGGTGGAGATCCCCATGTGCCGCGGCATCGGCTACAACCTGACCCGCATGCCCAACCT
GCTGGGCCACACGTCGCAGGGCGAGGCGGCTGCCGAGCTAGCGGAGTTCGCGCCGCTGGTGCAGTACG
GCTGCCACAGCCACCTCCGCTTCTTCCTGTGCTCGCTCTACGCGCCCATGTCCACCGACCAGGTCTCG
ACGCCCATTCCCGCCTGCCGGCCCATGTGCGAGCAGGCGCGCCTGCGCTGCGCGCCCATCATGGAGCA
GTTCAACTTCGCCTGGCCGGACTCGCTCGACTGCGCCCGGCTGCCCACGCGCAACGACCCGCACGCGC
TGTGCATGGAGGCGCCCGAGAACGCCACGGCCGGCCCCGCGGAGCCCCACAAGGGCCTGGGCATGCTG
CCCGTGGCGCCGCGGCCCGCGCGCCCTCCCGGAGACCTGGGCCCGGGCGCGGGCGGCAGTCGCACCTG
CGAGAACCCCGAGAAGTTCCAGTACGTGGAGAAGAGCCGCTCGTGCGCACCGCGCTGCCGGCCCGGCG
TCGAGGTGTTCTGGTCCCGGCGCGACAAGGACTTCGCGCTGGTCTGGATGGCCGTGTGGTCGGCGCTG
TGCTTCTTCTCCACCGCCTTCACTGTGCTCACCTTCTTGCTGGAGCCCCACCGCTTCCAGTACCCCGA
GCGCCCCATCATCTTCCTCTCCATGTGCTACAACGTCTACTCGCTGGCCTTCCTGATCCGTGCGGTGG
CCGGAGCGCAGAGCGTGGCCTGTCACCAGGAGGCGGGCGCGCTCTACGTGATCCAGGAGGGCCTGGAC
AACACGGGCTGCACGCTGGTCTTCCTACTGCTCTACTACTTCGGCATGGCCAGCTCGCTCTGGTGGGT
GGTCCTGACGCTCACCTGGTTCCTGGCTGCCGGGAAGAAATGGGGCCACGAGGCCATCGAGGCCCACG
GCAGCTATTTCCACATGGCTGCCTGGGGCCTGCCCGCGCTCAAGACCATCGTCATCCTGACCCTGCGC
AAGGTGGCGGGTGATGAGCTGACTGGGCTTTGCTACGTGGCCAGCACGGATGCAGCAGCGCTCACGGG
CTTCGTGCTGGTGCCCCTCTCTGGCTACCTGGTGCTGGGCAGTAGTTTCCTCCTGACCGGCTTCGTGG
CCCTCTTCCACATCCGCAAGATCATGAAGACGGGCGGCACCAACACAGAGAAGCTGGAGAAGCTCATG
GTCAAGATCGGGGTCTTCTCCATCCTCTACACGGTGCCCGCCACCTGCGTCATCGTTTGCTATGTCTA
CGAACGCCTCAACATGGACTTCTGGCGCCTTCGGGCCACAGAGCAGCCATGCGCAGCGGCCGCGGGGC
CCGGAGGCCGGAGGGACTGCTCGCTGCCAGGGGGCTCGGTGCCCACCGTGGCGGTCTTCATGCTCAAA
ATTTTCATGTCACTGGTGGTGGGGATCACCAGCGGCGTCTGGGTGTGGAGCTCCAAGACTTTCCAGAC
CTGGCAGAGCCTGTCCTACCGCAAGATAGCAGCTGCCCGGGCCCGGGCCAAGGCCTGCCGCGCCCCCG
GGAGCTACGGACGTGGCACGCACTGCCACTATAAGGCTCCCACCGTGGTCTTGCACATGACTAACACG
GACCCCTCTTTGGAGAACCCCACACACCTCTAGCCACACAGGCCTGGCGCGGGGTGGCTGCTGCCCCC
TCCTTGCCCTCCACGCCCTGCCCCCTGCATCCCCTAGAGACAGCTGACTAGCACCTGCCCAGCTGTCA
AGGTCAGGCAAGTGAGCACCGGGGACTGAGGATCAGGGCGGGACCCCGTGAGGCTCATTAGGGGAGAT
GGGGGTCTCCCCTAATGCGGGGGCTGGACCAGGCTGAGTCCCCACAGGGTCCTAGTGGAGGATGTGGA
GGGGCGCGGCAGAGGGGTCCAGCCGGAGTTTATTTAATGATGTAATTTATTGTTGCCTTCCTCTGGAA
GCTGTGACTGGAATAAACCCCCGCGTGGCACTGCTGATCCTCTCTGGCTGGGAAGGGGGAAGGTAGGA
GGTCAGGC
NOV7a, CG55690-01
Protein Sequence	SEQ ID NO: 88	591 aa	MW at 64465.5kD
MAVAPLRGALLLWQLLAAGGAALEIGRFDPERGRGAAPCQAVEIPMCRGIGYNLTRMPNLLGHTSQGE
AAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTDQVSTPIPACRPMCEQARLRCAPIMEQFNFGWPDS
LDCARLPTRNDPHALCMEAPENATAGPAEPHKGLGMLPVAPRPARPPGDLGPGAGGSGTCENPEKFQY
VEKSRSCAPRCGPGVEVFWSRRDKDFALVWMAVWSALCFFSTAFTVLTFLLEPHRFQYPERPIIFLSM
CYNVYSLAFLIRAVAGAQSVACDQEAGALYVIQEGLENTGCTLVFLLLYYFGMASSLWWVVLTLTWFL
AAGKKWGHEAIEAHGSYFHMAAWGLPALKTIVILTLRKVAGDELTGLCYVASTDAAALTGFVLVPLSG
YLVLGSSFLLTGFVALFHIRKIMKTGGTNTEKLEKLMVKIGVFSILYTVPATCVIVCYVYERLNMDFW
RLRATEQPCAAAAGPGGRRDCSLPGGSVPTVAVFMLKIFMSLVVGITSGVWVWSSKTFQTWQSLCYRK
IAAGRARAKACRAPGSYGRGTHCHYKAPTVVLHMTKTDPSLENPTNL
NOV7b, 224699969	SEQ ID NO: 89	438 bp
DNA Sequence	ORF Start: at 1	ORF Stop: at 439
GGATCCCTGGAGATCGGCCGCTTCGACCCGGAGCGCGGGCGCGGGGCTGCGCCGTGCCAGCCGGTGGA
GATCCCCATGTGCCGCGGCATCGGCTACAACCTGACCCGCATGCCCAACCTGCTGGGCCACACGTCGC
AGGGCGAGGCGGCTGCCGAGCTAGCGGAGTTCGCGCCGCTGGTGCAGTACGGCTGCCACAGCCACCTG
CGCTTCTTCCTGTGCTCGCTCTACGCGCCCATGTGCACCGACCAGGTCTCGACGCCCATTCCCGCGCG
CCCTCCCGGAGACCTGGGCCCGGGCGCGGGCGGCAGTGGCACCTGCGAGAACCCCGAGAAGTTCCAGT
ACGTGGAGAAGAGCCGCTCGTGCGCACCGCGCTGCGGGCCCGGCGTCGAGGTGTTCTGGTCCCGGCGC
GACAACGACTTCGCGCTGGTCTGGCTCGAG
NOV7b, 224699969
Protein Sequence	SEQ ID NO: 90	146 aa	MW at 15831.8kD
GSLEIGRFDPERGRGAAPCQAVEIPMCRGIGYNLTRMPNLLGHTSQGEAAAELAEFAPLVQYGCHSHL
RFFLCSLYAPMCTDQVSTPIPARPPGDLGPGAGGSGTCENPEKFQYVEKSRSCAPRCGPGVEVFWSRR
DKDFALVWLE
NOV7c, 219938152	SEQ ID NO: 91	441 bp
DNA Sequence	ORF Start: at 1	ORF Stop: end of sequence
GGATCCCTGGAGATCGGCCGCTTCGACCCGGAGCGCGGGCGCGGGGCTGCGCCGTGCCAGGCGGTGGA
GATCCCCATGTGCCGCGGCATCGGCTACAACCTGACCCGCATGCCCAACCTGCTGGGCCACACGTCGC
AGGGCGAGGCGGCTGCCGAGCTAGCGGAGTTCGCGCCGCTGGTGCAGTACGGCTGCCACAGCCACCTG
CGCTTCTTCCTGTGCTCGCTCTACGCGCCCATGTGCACCGACCAGGTCTCGACGCCCATTCCCGCCTG
CCGGCCCATGTGCGAGCAGGCGCGCCTGCGCTGCGCGCCCATCATGGAGCAGTTCAACTTCGGCTGGC
CGGACTCGCTCGACTGCGCCCGGCTGCCCACGCGCTGCGGGCCCGGCGTCGAGGTGTTCTGGTCCCGG
CGCGACAAGGACTTCGCGCTGGTCTGGCTCGAG
NOV7c, 219938152
Protein Sequence	SEQ ID NO: 92	147 aa	MW at 16395.7kD
GSLEIGRFDPERGRGAAPCQAVEIPMCRGIGYNLTRMPNLLGHTSQGEAAAELAEFAPLVQYGCHSHL
RFFLCSLYAPMCTDQVSTPIPACRPMCEQARLRCAPIMEQFNFGWPDSLDCARLPTRCGPGVEVFWSR
RDKDFALVWLE
NOV7d, 219938158	SEQ ID NO: 93	1437 bp
DNA Sequence	ORF Start: at 1	ORF Stop: end of sequence
GGATCCCTGGAGATCGGCCGCTTCCACCCGGAGCGCGGGCGCGGGGCTGCGCCGTGCCAGGCGGTGGA
GATCCCCATGTGCCGCGGCATCGGCTACAACCTGACCCGCATGCCCAACCTGCTGGGCCACACGTCGC
AGGGCGAGGCGGCTGCCGAGCTAGCGGAGTTCGCGCCGCTGGTGCAGTACGGCTGCCACAGCCACCTG
CGCTTCTTCCTGTGCTCGTTCTACGCGCCCATGTGCACCTGCGAGAACCCCGAGAAGTTCCAGTACGT
GGAGAAGAGCCGCTCGTGCGCACCGCGCTGCGGGCCCGGCGTCGAGGTGTTCTGGTCCCGGCGCGACA
AGGACTTCGCGCTGGTCTGGATGGCCGTGTGGTCGGCGCTGTGCTTCTTCTCCACCGCCTTCACTGTG
CTCACCTTCTTGCTGGAGCCCCACCGCTTCCAGTACCCCGAGCGCCCCATCATCTTCCTCTCCATGTG
CTACAACGTCTACTCGCTGGCCTTCCTGATCCGTGCGGTGGCCGGAGCGCAGAGCGTGGCCTGTGACC
AGGAGGCGGGCGCGCTCTACGTGATCCAGGAGGGCCTGGAGAACACGGGCTGCACGCTGGTCTTCCTA
CTGCTCTACTACTTCGGCATGGCCAGCTCGCTCTGGTGGGTGGTCCTGACGCTCACCTGGTTCCTGGC
TGCCGGGAAGAAATGGGGCCACGAGGCCATCGAGGCCCACGGCAGCTATTTCCACATGGCTGCCTGGG
GCCTGCCCGCGCTCAACACCATCGTCATCCTGACCCTGCGCAAGGTGGCGGGTGATGAGCTGACTGGG
CTTTGCTACGTGGCCAGCACGGATGCAGCAGCGCTCACGGGCTTCGTGCTGGTGCCCCTCTCTGGCTA
CCTGGTGCTGGGCAGTAGTTTCCTCCTGACCGGCTTCGTGGCCCTCTTCCACATCCGCAAGATCATGA
AGACGGGCGCCACCAACACAGAGAAGCTGGAGAAGCTCATGGTCAAGATCGGGGTCTTCTCCATCCTC
TACACGGTGCCCGCCACCTGCGTCATCGTTTGCTATGTCTACGAACGCCTCAACATGGACTTCTGGCG
CCTTCGGGTCACAGAGCAGCCATGCGCAGCGGCCGCGGGGCCCGGAGGCCGGAGGGACTGCTCGCTGC
CAGGGGGCTCGGTGCCCACCGTGGCGGTCTTCATGCTCAAAATTTTCATGTCACTGGTGGTGGGGATC
ACCAGCGGCGTCTGGGTGTGGAGCTCCAAGACTTTCCAGACCTGGCAGAGCCTGTGCTACCGCAAGAT
AGCAGCTGGCCGGGCCCGGGCCAAGGCCTGCCGCGCCCCCGGGAGCTACGGACGTGGCACGCACTGCC
ACTATAAGGCTCCCACCGTCGTCTTGCACATGACTAAGACGGACCCCTCTTTGGAGAACCCCACACAC
CTCCTCGAG
NOV7d, 219938158
Protein Sequence	SEQ ID NO: 94	479 aa	MW at 52944.3kD
GSLEIGRFDPERGRGAAPCQAVEIPMCRGIGYNLTRMPNLLGHTSQGEAAAELAEFAPLVQYGCHSHL
RFFLCSFYAPMCTCENPEKFQYVEKSRSCAPRCGPGVEVFWSRRDKDFALVWMAVWSALCFFSTAFTV
LTFLLEPHRFQYPERPIIFLSMCYNVYSLAFLIRAVAGAQSVACDQEAGALYVIQEGLENTGCTLVFL
LLYYFGMASSLWWVVLTLTWFLAAGKKWGHEAIEAHGSYFHMAAWGLPALKTIVILTLRKVAGDELTG
LCYVASTDAAALTGFVLVPLSGYLVLGSSFLLTGFVALFHIRKIMKTGGTNTEKLEKLMVKIGVFSIL
YTVPATCVIVCYVYERLNMDFWRLRVTEQPCAAAAGPGGRRDCSLPGGSVPTVAVFMLKIFMSLVVGI
TSGVWVWSSKTFQTWQSLCYRKIAAGRARAKACRAPGSYGRGTHCHYKAPTVVLHMTKTDPSLENPTH
LLE
NOV7e, CG55690-02	SEQ ID NO: 95	1787 bp
DNA Sequence	ORF Start: ATG at 1	ORF Stop: end of sequence
ATGGCCGTGGCGCCTCTGCGGGGGGCGCTGCTCCTGTGGCAGCTGCTGGCGGCGGGCGGCGCGGCACT
GGAGATCGGCCGCTTCGACCCGGAGCGCGGGCGCGGGGCTGCGCCGTGCCAGGCCGTGGAGATCCCCA
TGTGCCGCGGCATCGGCTACAACCTGACCCGCATGCCCAACCTGCTGGGCCACACGTCGCAGGGCGAG
GCGGCTGCCGAGCTAGCGGAGTTCGCGCCGCTGGTGCAGTACGGCTGCCACAGCCACCTGCGCTTCTT
CCTGTGCTCGCTCTACGCGCCCATGTGCACCGACCAGGTCTCGACGCCCATTCCCGCCTGCCGGCCCA
TGTGCGAGCAGGCGCGCCTGCGCTGCGCGCCCATCATGGAGCAGTTCAACTTCGGCTGGCCGGACTCG
CTCGACTGCGCCCGGCTGCCCACGCGCAACGACCCGCACGCGCTGTGCATGGAGGCGCCCGAGAACGC
CACGGCCGGCCCCGCGGAGCCCCACAAGGGCCTGGGCATGCTGCCCGTGGCGCCGCGGCCCGCGCGCC
CTCCCGGAGACCTGGGCCCGGGCGCGGGCGGCAGTGGCACCTGCGAGAACCCCGAGAAGTTCCAGTAC
GTGGAGAAGAGCCGCTCGTGCGCACCGCGCTGCGGGCCCGGCGTCGAGGTGTTCTGGTCCCGGCGCGA
CAAGGACTTCGCGCTGGTCTGGATGGCCGTGTGGTCGGCGCTGTGCTTCTTCTCCACCGCCTTCACTG
TGCTCACCTTCTTGCTGGAGCCCCACCGCTTCCAGTACCCCGAGCGCCCCATCATCTTCCTCTCCATG
TGCTACAACGTCTACTCGCTGGCCTTCCTGATCCGTGCGGTGGCCGGAGCGCAGAGCGTGGCCTGTGA
CCAGGAGGCGGGCGCGCTCTACGTGATCCAGGAGGGCCTGGAGAACACGGGCTGCACGCTGGTCTTCC
TACTGCTCTACTACTTCGGCATGGCCAGCTCGCTCTGGTGGGTGGTCCTGACGCTCACCTGGTTCCTG
GCTGCCGGGAAGAAATGGGGCCACGAGGCCATCGAGGCCCACGGCAGCTATTTCCACATGGCTGCCTG
GGGCCTGCCCGCGCTCAAGACCATCGTCATCCTGACCCTGCGCAAGGTGGCGGGTGATGAGCTGACTG
GGCTTTGCTACGTGGCCAGCACGGATGCAGCAGCGCTCACGGGCTTCGTGCTGGTGCCCCTCTCTGGC
TACCTGGTGCTGGGCAGTAGTTTCCTCCTGACCGGCTTCGTGGCCCTCTTCCACATCCCCAAGATCAT
GAAGACGGGCGCCACCAACACAGAGAAGCTGGAGAAGCTCATGGTCAAGATCGGGGTCTTCTCCATCC
TCTACACGGTGCCCGCCACCTGCGTCATCGTTTGCTATGTCTACGAACGCCTCAACATGGACTTCTGG
CGCCTTCGGGCCACAGAGCAGCCATGCGCAGCGGCCGCGGGGCCCGGAGGCCGGAGGGACTGCTCGCT
GCCAGGGGGCTCGGTGCCCACCGTGGCGGTCTTCATGCTCAAAATTTTCATGTCACTGGTGGTGGGGA
TCACCAGCGGCGTCTGGGTGTGGAGCTCCAAGACTTTCCAGACCTGGCAGAGCCTGTGCTACCGCAAG
ATACCAGCTGGCCGGGCCCGGGCCAAGGCCTGCCGCGCCCCCGGGAGCTACGGACGTGGCACCCACTG
CCACTATAAGGCTCCCACCGTGGTCTTGCACATGACTAAGACGGACCCCTCTTTGGAGAACCCCACAC
ACCTCTAGCCACACAGGCC
NOV7e, CG55690-02
Protein Sequence	SEQ ID NO: 96	591 aa	MW at 64465.5kD
MAVAPLRGALLLWQLLAAGGAALEIGRFDPERGRGAAPCQAVEIPMCRGIGYNLTRMPNLLGHTSQGE
AAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTDQVSTPIPACRPMCEQARLRCAPIMEQFNFGWPDS
LDCARLPTRNDPHALCMEAPENATAGPAEPHKGLGMLPVAPRPARPPGDLGPGAGGSGTCENPEKFQY
VEKSRSCAPRCGPGVEVFWSRRDKDFALVWMAVWSALCFFSTAFTVLTFLLEPHRFQYPERPIIFLSM
CYNVYSLAFLIRAVAGAQSVACDQEAGALYVIQEGLENTGCTLVFLLLYYFGMASSLWWVVLTLTWFL
AAGKKWGHEAIEAHGSYFHMAAWGLPALKTIVILTLRKVAGDELTGLCYVASTDAAALTGFVLVPLSG
YLVLGSSFLLTGFVALFHIRKIMKTGGTNTEKLEKLMVKIGVFSILYTVPATCVIVCYVYERLNMDFW
RLRATEQPCAAAAGPGGRRDCSLPGGSVPTVAVFMLKIFMSLVVGITSGVWVWSSKTFQTWQSLCYRK
IAAGRARAKACRAPGSYGRGTHCHYKAPTVVLHMTKTDPSLENPTHL
NOV7f, CG55690-03	SEQ ID NO: 97	1437 bp
DNA Sequence	ORF Start: at 7	ORF Stop: end of sequence
GGATCCCTGCAGATCGGCCGCTTCGACCCGGAGCGCGGGCGCGGGGCTGCGCCGTGCCAGGCGGTGGA
GATCCCCATGTGCCGCGGCATCGGCTACAACCTGACCCGCATGCCCAACCTGCTGGGCCACACGTCGC
AGGGCGAGGCGGCTGCCGAGCTAGCGGAGTTCGCGCCGCTGGTGCAGTACGGCTGCCACAGCCACCTG
CGCTTCTTCCTGTGCTCGTTCTACGCGCCCATGTGCACCTGCGAGAACCCCGAGAAGTTCCAGTACGT
GGAGAAGAGCCGCTCGTGCGCACCGCGCTGCGGGCCCGGCGTCGAGGTGTTCTGGTCCCGGCGCGACA
AGGACTTCGCGCTGGTCTGGATGGCCGTGTGGTCCGCGCTGTGCTTCTTCTCCACCGCCTTCACTGTG
CTCACCTTCTTGCTGGAGCCCCACCGCTTCCAGTACCCCGAGCGCCCCATCATCTTCCTCTCCATGTG
CTACAACGTCTACTCGCTGGCCTTCCTGATCCGTGCGGTGGCCGGAGCGCAGAGCGTGGCCTGTGACC
AGGAGGCGGGCGCGCTCTACGTGATCCAGGAGGGCCTGGAGAACACGGGCTGCACGCTGGTCTTCCTA
CTGCTCTACTACTTCGGCATGGCCAGCTCGCTCTGGTGGGTGGTCCTGACGCTCACCTGGTTCCTGGC
TGCCGGGAAGAAATGCGGCCACGAGGCCATCGAGGCCCACGGCAGCTATTTCCACATGGCTGCCTGGG
GCCTGCCCGCGCTCAAGACCATCGTCATCCTGACCCTGCGCAAGGTGGCGGGTGATGAGCTGACTGGG
CTTTGCTACGTGGCCAGCACGGATGCAGCAGCGCTCACGGGCTTCGTGCTGGTGCCCCTCTCTGGCTA
CCTGGTGCTGGGCAGTAGTTTCCTCCTGACCGGCTTCGTGGCCCTCTTCCACATCCGCAAGATCATGA
AGACGGGCGGCACCAACACAGAGAAGCTGGAGAAGCTCATGGTCAAGATCGGGGTCTTCTCCATCCTC
TACACGGTGCCCGCCACCTGCGTCATCGTTTGCTATGTCTACGAACGCCTCAACATGGACTTCTGGCG
CCTTCGGGTCACAGAGCAGCCATGCGCAGCGGCCGCGGGGCCCGGAGGCCGGAGGGACTGCTCGCTGC
CAGGGGGCTCGGTGCCCACCGTGGCGGTCTTCATGCTCAAAATTTTCATGTCACTGGTGGTGGGGATC
ACCAGCGGCGTCTGGGTGTGGAGCTCCAAGACTTTCCAGACCTGGCAGAGCCTGTGCTACCGCAAGAT
AGCAGCTGGCCGGGCCCGGGCCAAGGCCTGCCGCGCCCCCGGGAGCTACGGACGTGGCACGCACTGCC
ACTATAAGGCTCCCACCGTGGTCTTGCACATGACTAAGACGGACCCCTCTTTGGAGAACCCCACACAC
CTCCTCGAG
NOV7f, CG55690-03
Protein Sequence	SEQ ID NO: 98	475 aa	MW at 52557.9kD
LEIGRFDPERGRGAAPCQAVEIPMCRGIGYNLTRMPNLLGHTSQGEAAAELAEFAPLVQYGCHSHLRF
FLCSFYAPMCTCENPEKFQYVEKSRSCAPRCGPGVEVFWSRRDKDFALVWMAVWSALCFFSTAFTVLT
FLLEPHRFQYPERPIIFLSMCYNVYSLAFLIRAVAGAQSVACDQEAGALYVIQEGLENTGCTLVFLLL
YYFGMASSLWWVVLTLTWFLAAGKKWGHEAIEAHGSYFHMAAWGLPALKTIVILTLRKVAGDELTGLC
YVASTDAAALTGFVLVPLSGYLVLGSSFLLTGFVALFHIRKIMKTGGTNTEKLEKLMVKIGVFSILYT
VPATCVIVCYVYERLNMDFWRLRVTEQPCAAAAGPGGRRDCSLPGGSVPTVAVFMLKIFMSLVVGITS
GVWVWSSKTFQTWQSLCYRKIAAGRARAKACRAPGSYGRGTHCHYKAPTVVLHMTKTDPSLENPTHL
NOV7g, CG55690-04	SEQ ID NO: 99	441 bp
DNA Sequence	ORF Start: at 7	ORF Stop: at 436
GGATCCCTGGAGATCGGCCGCTTCGACCCGGAGCGCGGGCGCGGCGCTGCGCCGTGCCAGGCGGTGGA
GATCCCCATGTGCCGCGGCATCGGCTACAACCTGACCCGCATGCCCAACCTGCTGGGCCACACGTCGC
AGGGCGAGGCGCCTGCCGAGCTAGCGGAGTTCGCGCCGCTGGTGCAGTACGGCTGCCACAGCCACCTG
CGCTTCTTCCTGTGCTCGCTCTACGCGCCCATGTGCACCGACCAGGTCTCGACGCCCATTCCCGCCTG
CCGGCCCATGTGCGAGCAGGCGCGCCTGCGCTGCGCGCCCATCATGGAGCAGTTCAACTTCGGCTGGC
CGGACTCGCTCGACTGCGCCCGGCTGCCCACGCGCTGCGGGCCCGGCGTCGAGGTGTTCTGGTCCCGG
CGCGACAAGGACTTCGCGCTGGTCTGGCTCGAG
NOV7g, CG55690-04
Protein Sequence	SEQ ID NO: 100	143 aa	MW at 16009.3kD
LEIGRFDPERGRGAAPCQAVEIPMCRGIGYNLTRMPNLLGHTSQGEAAAELAEFAPLVQYGCHSHLRF
FLCSLYAPMCTDQVSTPIPACRPMCEQARLRCAPIMEQFNFGWPDSLDCARLPTRCGPGVEVFWSRRD
KDFALVW
NOV7h, CG55690-05	SEQ ID NO: 101	438 bp
DNA Sequence	ORF Start: at 7	ORF Stop: end of sequence
GGATCCCTGGAGATCGGCCGCTTCGACCCGGAGCGCGGGCGCGGGGCTGCGCCGTGCCAGGCGGTGGA
GATCCCCATGTGCCGCGGCATCGGCTACAACCTGACCCGCATGCCCAACCTGCTGGGCCACACGTCGC
AGGGCGAGGCGGCTGCCGAGCTAGCGGAGTTCGCGCCGCTGGTGCAGTACGGCTGCCACAGCCACCTG
CGCTTCTTCCTGTGCTCGCTCTACGCGCCCATGTGCACCGACCAGGTCTCGACGCCCATTCCCGCGCG
CCCTCCCGGAGACCTGGGCCCGGGCGCGGGCGGCAGTGGCACCTGCGAGAACCCCGAGAAGTTCCAGT
ACGTGGAGAAGAGCCGCTCGTGCGCACCGCGCTGCGGGCCCGGCGTCGAGGTGTTCTGGTCCCGGCGC
GACAAGGACTTCCCGCTGGTCTGGCTCGAG
NOV7h, CG55690-05
Protein Sequence	SEQ ID NO: 102	142 aa	MW at 15445.4kD
LEIGRFDPERGRGAAPCQAVEIPMCRGIGYNLTRMPNLLGHTSQGEAAAELAEFAPLVQYGCHSHLRF
FLCSLYAPMCTDQVSTPIPARPPGDLGPGAGGSGTCENPEKFQYVEKSRSCAPRCGPGVEVFWSRRDK
DFALVW

[0415] The NOV7i 13376520 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 7B.

TABLE 7B
NOV7i Sequence Analysis
NOV7i 13376520	SEQ ID NO: 103	2184 bp
DNA Sequence	ORF Start: ATG at 26	ORF Stop: end of sequence
CCGCCTTCGGCCCGGGCCTCCCGGGATGGCCGTGGCGCCTCTGCGGGGGGCGCTGCTGCTGTGGCAGC
TGCTCGCGGCGGGCGGCGCGGCACTGGAGATCGGCCGCTTCGACCCGGAGCGCGGGCGCGGGGCTGCG
CCGTGCCAGGCGGTGGAGATCCCCATGTGCCGCGGCATCCGCTACAACCTGACCCGCATGCCCAACCT
GCTGGGCCACACGTCGCAGGGCGAGGCGGCTGCCGAGCTAGCGGAGTTCGCGCCGCTGGTGCAGTACG
GCTGCCACAGCCACCTGCGCTTCTTCCTGTGCTCGCTCTACGCGCCCATGTGCACCGACCAGGTCTCG
ACGCCCATTCCCGCCTGCCGGCCCATGTGCGAGCAGGCGCGCCTGCGCTGCGCGCCCATCATGGAGCA
GTTCAACTTCGGCTGGCCGGACTCGCTCGACTGCGCCCGGCTGCCCACGCGCAACGACCCGCACGCGC
TGTGCATGGACGCGCCCGAGAACGCCACGGCCGGCCCCGCGGAGCCCCACAAGGGCCTGGGCATGCTC
CCCGTGGCGCCGCGGCCCGCGCGCCCTCCCGGAGACCTGGGCCCGGGCGCGGGCGGCAGTGGCACCTG
CGAGAACCCCGAGAAGTTCCAGTACGTGGAGAAGAGCCGCTCGTGCGCACCGCGCTGCGGGCCCGGCG
TCGAGGTGTTCTGGTCCCGGCGCGACAAGGACTTCGCGCTGGTCTGGATGCCCGTGTGGTCGGCGCTG
TGCTTCTTCTCCACCGCCTTCACTGTGCTCACCTTCTTGCTGGAGCCCCACCGCTTCCAGTACCCCGA
GCGCCCCATCATCTTCCTCTCCATGTGCTACAACGTCTACTCGCTGGCCTTCCTGATCCCTGCGGTGG
CCGGAGCGCAGAGCGTGGCCTGTGACCAGGAGGCGGGCGCGCTCTACGTGATCCAGGAGGGCCTGGAG
AACACGGGCTGCACGCTGGTCTTCCTACTGCTCTACTACTTCGGCATGGCCAGCTCGCTCTGGTGGGT
GGTCCTGACGCTCACCTGGTTCCTGGCTGCCGGGAAGAAATGGGGCCACGAGGCCATCGAGGCCCACG
GCAGCTATTTCCACATGGCTGCCTGGGGCCTGCCCGCGCTCAAGACCATCGTCATCCTGACCCTGCGC
AAGGTGGCGGGTGATGAGCTGACTGGGCTTTGCTACGTGGCCAGCACGGATGCAGCAGCGCTCACGGG
CTTCGTGCTGGTGCCCCTCTCTGGCTACCTGGTGCTCGGCAGTAGTTTCCTCCTGACCGGCTTCGTGG
CCCTCTTCCACATCCGCAAGATCATGAAGACGGGCGGCACCAACACAGAGAAGCTGGGGAAGCTCATG
GTCAAGATCGCGGTCTTCTCCATCCTCTACACGGTGCCCGCCACCTGCGTCATCGTTTGCTATGTCTA
CGAACGCCTCAACATGGACTTCTGGCGCCTTCGGGCCACAGAGCAGCCATGCGCAGCGGCCGCGGGGC
CCGGAGGCCGGAGGGACTGCTCGCTGCCAGGGGGCTCGGTGCCCACCGTGGCGGTCTTCATGCTCAAA
ATTTTCATGTCACTGGTGGTGGGGATCACCAGCGGCGTCTGGGTGTGGAGCTCCAAGACTTTCCAGAC
CTGGCAGAGCCTGTGCTACCCCAAGATAGCAGCTGGCCGGGCCCGGGCCAAGGCCTGCCGCGCCCCCG
GGAGCTACGGACGTGGCACGCACTGCCACTATAAGGCTCCCACCGTGGTCTTGCACATGACTAAGACG
GACCCCTCTTTGGAGAACCCCACACACCTCTAGCCACACAGGCCTGGCGCGGGGTGGCTGCTGCCCCC
TCCTTGCCCTCCACGCCCTGCCCCCTGCATCCCCTACAGACAGCTGACTAGCAGCTGCCCAGCTGTCA
AGGTCAGGCAAGTGAGCACCGGCGACTGAGGATCAGGGCGGGACCCCGTGAGGCTCATTAGGGGAGAT
GGGGGTCTCCCCTAATGCGGGGGCTGGACCAGGCTGAGTCCCCACAGGGTCCTAGTGGAGGATGTGGA
GGGGCGGGGCAGAGGGGTCCAGCCGGAGTTTATTTAATGATGTAATTTATTGTTGCGTTCCTCTGGAA
GCTGTGACTGGAATAAACCCCCGCGTGGCACTGCTGATCCTCTCTGGCTGGGAAGGGGGAAGGTAGGA
GGTGAGGC
NOV7i 13376520
Protein Sequence	SEQ ID NO: 104	591 aa	MW at 64465.5kD
MAVAPLRGALLLWQLLAAGGAALEIGRFDPERGRGAAPCQAVEIPMCRGIGYNLTRMPNLLGHTSQGE
AAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTDQVSTPIPACRPMCEQARLRCAPIMEQFNFGWPDS
LDCARLPTRNDPHALCMEAPENATAGPAEPHKGLGMLPVAPRPARPPGDLGPGAGGSGTCENPEKFQY
VEKSRSCAPRCGPGVEVFWSRRDKDFALVWMAVWSALCFFSTAFTVLTFLLEPHRFQYPERPIIFLSM
CYNVYSLAFLIRAVAGAQSVACDQEAGALYVIQEGLENTGCTLVFLLLYYFGMASSLWWVVLTLTWFL
AAGKKWGHEAIEAHGSYFHMAAWGLPALKTIVILTLRKVAGDELTGLCYVASTDAAALTGFVLVPLSG
YLVLGSSFLLTGFVALFHIRKIMKTGGTNTEKLGKLMVKIGVFSILYTVPATCVIVCYVYERLNMDFW
RLRATEQPCAAAAGPGGRRDCSLPGGSVPTVAVFMLKIFMSLVVGITSGVWVWSSKTFQTWQSLCYRK
IAAGRARAKACRAPGSYGRGTHCHYKAPTVVLHMTKTDPSLENPTHL

[0416] The NOV7j 13376521 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 7C.

TABLE 7C
NOV7j Sequence Analysis
NOV7j, 13376521	SEQ ID NO: 105	2184 bp
DNA Sequence	ORF Start: ATG at 26	ORF Stop: end of sequence
CCGCCTTCGGCCCGGGCCTCCCGGGATGGCCGTGGCGCCTCTGCGGGGGGCGCTGCTGCTGTGGCAGC
TGCTGGCGGCGGGCGGCGCGGCACTGGAGATCGGCCGCTTCGACCCGGAGCGCGGGCGCGGGGCTGCG
CCGTGCCAGGCGGTGGAGATCCCCATGTGCCGCGGCATCGGCTACAACCTGACCCGCATGCCCAACCT
GCTGGGCCACACGTCGCAGGGCGAGGCGGCTGCCGAGCTAGCGGAGTTCGCGCCGCTGGTGCAGTACG
GCTGCCACAGCCACCTGCGCTTCTTCCTGTGCTCGCTCTACGCGCCCATGTGCACCGACCAGGTCTCG
ACGCCCATTCCCGCCTGCCGGCCCATGTGCCACCAGGCGCGCCTGCGCTGCGCGCCCATCATGGAGCA
GTTCAACTTCGGCTGGCCGGACTCGCTCGACTGCGCCCGGCTGCCCACGCGCAACGACCCGCACGCGC
TGTGCATGGAGGCGCCCGAGAACGCCACGGCCGGCCCCGCGGAGCCCCACAAGGGCCTGGGCATGCTG
CCCGTGGCGCCGCGGCCCGCGCGCCCTCCCGGAGACCTGGGCCCCGGCGCGGGCGGCAGTGGCACCTG
CGAGAACCCCGAGAAGTTCCAGTACGTGGAGAAGAGCCGCTCGTGCGCACCGCGCTGCGGGCCCGGCG
TCGAGGTGTTCTGGTCCCGGCGCGACAAGGACTTCGCGCTGGTCTGGATGGCCGTGTGGTCGGCGCTG
TGCTTCTTCTCCACCGCCTTCACTGTGCTCACCTTCTTGCTGGAGCCCCACCGCTTCCAGTACCCCGA
GCGCCCCATCATCTTCCTCTCCATGTGCTACAACGTCTACTCGCTGGCCTTCCTGATCCGTGCGGTGG
CCGGAGCGCAGAGCGTGGCCTGTGACCAGGAGGCGGGCGCGCTCTACGTGATCCAGGAGGGCCTGGAG
AACACGGGCTGCACGCTGGTCTTCCTACTGCTCTACTACTTCGGCATGGCCAGCTCGCTCTGGTGGGT
GGTCCTGACGCTCACCTGGTTCCTGGCTGCCGGGAAGAAATGGGGCCACGAGGCCATCGAGGCCCACG
GCAGCTATTTCCACATCGCTGCCTGGGGCCTGCCCGCGCTCAAGACCATCGTCATCCTGACCCTGCGC
AAGGTGGCGGGTGATCAGCTGACTGGGCTTTGCTACGTGGCCAGCACGGATGCAGCAGCGCTCACGGG
CTTCGTGCTGGTGCCCCTCTCTGGCTACCTGGTGCTGGGCAGTAGTTTCCTCCTGACCGGCTTCGTGG
CCCTCTTCCACATCCGCAAGATCATGAAGACGGGCGGCACCAACACAGAGAAGCTGGAGAAGCTCATG
GTCAAGATCGGGGTCTTCTCCATCCTCTACACGGTGCCCGCCACCTGCGTCATCGTTTGCTATGTCTA
CGAACGCCTCAACATGGACTTCTGGCGCCTTCGGGCCACAGAGCAGCCATGCGCAGCGGCCGCGGGGC
CCGGAGGCCGGAGGGACTGCTCGCTGCCAGGGGGCTCGGTGCCCACCGTGGCGGTCTTCATGCTCAAA
ATTTTCATGTCACTGGTGGTGGGGATCACCAGCGGCGCCTGGGTGTGGAGCTCCAAGACTTTCCAGAC
CTGGCAGAGCCTGTGCTACCGCAAGATAGCAGCTGGCCGGGCCCGGGCCAAGGCCTGCCGCGCCCCCG
GGAGCTACGGACGTGGCACGCACTGCCACTATAAGGCTCCCACCGTGGTCTTGCACATGACTAAGACG
GACCCCTCTTTGGAGAACCCCACACACCTCTAGCCACACAGGCCTGGCGCGGGGTGGCTGCTGCCCCC
TCCTTGCCCTCCACGCCCTGCCCCCTGCATCCCCTAGAGACAGCTGACTAGCAGCTGCCCAGCTGTCA
AGGTCAGGCAAGTGAGCACCGGGGACTGAGGATCAGGGCGGGACCCCGTGAGGCTCATTAGGGGAGAT
GGGGGTCTCCCCTAATGCGGGGGCTGGACCAGGCTGAGTCCCCACAGGGTCCTAGTGGAGGATGTGGA
GGGGCGGGGCAGAGGGGTCCAGCCGGAGTTTATTTAATGATGTAATTTATTGTTGCGTTCCTCTGGAA
GCTGTGACTGGAATAAACCCCCGCGTGGCACTGCTGATCCTCTCTGGCTGGGAAGGGGGAAGGTAGGA
GGTGAGGC
NOV7j, 13376521
Protein Sequence	SEQ ID NO: 106	591 aa	MW at 64465.5kD
MAVAPLRGALLLWQLLAAGGAALEIGRFDPERGRGAAPCQAVEIPMCRGIGYNLTRMPNLLGHTSQGE
AAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTDQVSTPIPACRPMCEQARLRCAPIMEQFNFGWPDS
LDCARLPTRNDPHALCMEAPENATAGPAEPHKGLGMLPVAPRPARPPGDLGPGAGGSGTCENPEKFQY
VEKSRSCAPRCGPGVEVFWSRRDKDFALVWMAVWSALCFFSTAFTVLTFLLEPHRFQYPERPIIFLSM
CYNVYSLAFLIRAVAGAQSVACDQEAGALYVIQEGLENTGCTLVFLLLYYFGMASSLWWVVLTLTWFL
AAGKKWGHEAIEAHGSYFHMAAWGLPALKTIVILTLRKVAGDELTGLCYVASTDAAALTGFVLVPLSG
YLVLGSSFLLTGFVALFHIRKIMKTGGTNTEKLEKLMVKIGVFSILYTVPATCVIVCYVYERLNMDFW
RLRATEQPCAAAAGPGGRRDCSLPGGSVPTVAVFMLKIFMSLVVGITSGAWVWSSKTFQTWQSLCYRK
IAAGRARAKACRAPGSYGRGTHCHYKAPTVVLHMTKTDPSLENPTHL

[0417] A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 7D.

TABLE 7D
Comparison of the NOV7 protein sequences.
NOV7a MAVAPLRGALLLWQLLAAGGAALEIGRFDPERGRGAAPCQAVEIPMCRGIGYNLTRMPNL
NOV7b --------------------GSLEIGRFDPERGRGAAPCQAVEIPMCRGIGYNLTRMPNL
NOV7c --------------------GSLEIGRFDPERGRGAAPCQAVEIPMCRGIGYNLTRMPNL
NOV7d --------------------GSLEIGRFDPERGRGAAPCQAVEIPMCRGIGYNLTRMPNL
NOV7e MAVAPLRGALLLWQLLAAGGAALEIGRFDPERGRGAAPCQAVEIPMCRGIGYNLTRMPNL
NOV7f ----------------------LEIGRFDPERGRGAAPCQAVEIPMCRGIGYNLTRMPNL
NOV7g ----------------------LEIGRFDPERGRGAAPCQAVEIPMCRGIGYNLTRMPNL
NOV7h ----------------------LEIGRFDPERGRGAAPCQAVEIPMCRGIGYNLTRMPNL
NOV7a LGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTDQVSTPIPACRPMCEQARL
NOV7b LGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTDQVSTPIPARPPGDLGPGA
NOV7c LGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTDQVSTPIPACRPMCEQARL
NOV7d LGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSFYAPMCT-------------------
NOV7e LGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTDQVSTPIPACRPMCEQARL
NOV7f LGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSFYAPMCT-------------------
NOV7g LGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTDQVSTPIPACRPMCEQARL
NOV7h LGHTSQGEAAAELAEFAPLVQYGCHSHLRFFLCSLYAPMCTDQVSTPIPARPPGDLGPGA
NOV7a RCAPIMEQFNFGWPDSLDCARLPTRNDPHALCMEAPENATAGPAEPHKGLGMLPVAPRPA
NOV7b GGSG--------------------------------------------------------
NOV7c R-----------------------------------------------------------
NOV7d ------------------------------------------------------------
NOV7e RCAPIMEQFNFGWPDSLDCARLPTRNDPHALCMEAPENATAGPAEPHKGLGMLPVAPRPA
NOV7f ------------------------------------------------------------
NOV7g R-----------------------------------------------------------
NOV7h GGSG--------------------------------------------------------
NOV7a RPPGDLGPGAGGSGTCENPEKFQYVEKS----RSCAPRCGPGVEVFWSRRDKDFALVWMA
NOV7b --------------TCENPEKFQYVEKS----RSCAPRCGPGVEVFWSRRDKDFALVWLE
NOV7c --------------CAPIMEQFNFGWPDSLDCARLPTRCGPGVEVFWSRRDKDFALVWLE
NOV7d ---------------CENPEKFQYVEKS----RSCAPRCGPGVEVFWSRRDKDFALVWMA
NOV7e RPPGDLGPGAGGSGTCENPEKFQYVEKS----RSCAPRCGPGVEVFWSRRDKDFALVWMA
NOV7f ---------------CENPEKFQYVEKS----RSCAPRCGPGVEVFWSRRDKDFALVWMA
NOV7g --------------CAPIMEQFNFGWPDSLDCARLPTRCGPGVEVFWSRRDKDFALVW--
NOV7h --------------TCENPEKFQYVEKS----RSCAPRCGPGVEVFWSRRDKDFALVW--
NOV7a VWSALCFFSTAFTVLTFLLEPHRFQYPERPIIFLSMCYNVYSLAFLIRAVAGAQSVACDQ
NOV7b ------------------------------------------------------------
NOV7c ------------------------------------------------------------
NOV7d VWSALCFFSTAFTVLTFLLEPHRFQYPERPIIFLSMCYNVYSLAFLIRAVAGAQSVACDQ
NOV7e VWSALCFFSTAFTVLTFLLEPHRFQYPERPIIFLSMCYNVYSLAFLIRAVAGAQSVACDQ
NOV7f VWSALCFFSTAFTVLTFLLEPHRFQYPERPIIFLSMCYNVYSLAFLIRAVAGAQSVACDQ
NOV7g ------------------------------------------------------------
NOV7h ------------------------------------------------------------
NOV7a EAGALYVIQEGLENTGCTLVFLLLYYFGMASSLWWVVLTLTWFLAAGKKWGHEAIEAHGS
NOV7b ------------------------------------------------------------
NOV7c ------------------------------------------------------------
NOV7d EAGALYVIQEGLENTGCTLVFLLLYYFGMASSLWWVVLTLTWFLAAGKKWGHEAIEAHGS
NOV7e EAGALYVIQEGLENTGCTLVFLLLYYFGMASSLWWVVLTLTWFLAAGKKWGHEAIEAHGS
NOV7f EAGALYVIQEGLENTGCTLVFLLLYYFGMASSLWWVVLTLTWFLAAGKKWGHEAIEAHGS
NOV7g ------------------------------------------------------------
NOV7h ------------------------------------------------------------
NOV7a YFHMAAWGLPALKTIVILTLRKVAGDELTGLCYVASTDAAALTGFVLVPLSGYLVLGSSF
NOV7b ------------------------------------------------------------
NOV7c ------------------------------------------------------------
NOV7d YFHMAAWGLPALKTIVILTLRKVAGDELTGLCYVASTDAAALTGFVLVPLSGYLVLGSSF
NOV7e YFHMAAWGLPALKTIVILTLRKVAGDELTGLCYVASTDAAALTGFVLVPLSGYLVLGSSF
NOV7f YFHMAAWGLPALKTIVILTLRKVAGDELTGLCYVASTDAAALTGFVLVPLSGYLVLGSSF
NOV7g ------------------------------------------------------------
NOV7h ------------------------------------------------------------
NOV7a LLTGFVALFHIRKIMKTGGTNTEKLEKLMVKIGVFSILYTVPATCVIVCYVYERLNMDFW
NOV7b ------------------------------------------------------------
NOV7c ------------------------------------------------------------
NOV7d LLTGFVALFHIRKIMKTGGTNTEKLEKLMVKIGVFSILYTVPATCVIVCYVYERLNMDFW
NOV7e LLTGFVALFHIRKIMKTGGTNTEKLEKLMVKIGVFSILYTVPATCVIVCYVYERLNMDFW
NOV7f LLTGFVALFHIRKIMKTGGTNTEKLEKLMVKIGVFSILYTVPATCVIVCYVYERLNMDFW
NOV7g ------------------------------------------------------------
NOV7h ------------------------------------------------------------
NOV7a RLRATEQPCAAAAGPGGRRDCSLPGGSVPTVAVFMLKIFMSLVVGITSGVWVWSSKTFQT
NOV7b ------------------------------------------------------------
NOV7c ------------------------------------------------------------
NOV7d RLRVTEQPCAAAAGPGGRRDCSLPGGSVPTVAVFMLKIFMSLVVGITSGVWVWSSKTFQT
NOV7e RLRATEQPCAAAAGPGGRRDCSLPGGSVPTVAVFMLKIFMSLVVGITSGVWVWSSKTFQT
NOV7f RLRVTEQPCAAAAGPGGRRDCSLPGGSVPTVAVFMLKIFMSLVVGITSGVWVWSSKTFQT
NOV7g ------------------------------------------------------------
NOV7h ------------------------------------------------------------
NOV7a WQSLCYRKIAAGRARAKACRAPGSYGRGTHCHYKAPTVVLHMTKTDPSLENPTHL--
NOV7b ---------------------------------------------------------
NOV7c ---------------------------------------------------------
NOV7d WQSLCYRKIAAGRARAKACRAPGSYGRCTHCHYKAPTVVLHMTKTDPSLENPTHLLE
NOV7e WQSLCYRKIAAGRARAKACRAPGSYGRGTHCHYKAPTVVLHMTKTDPSLENPTHL--
NOV7f WQSLCYRKIAAGRARAKACRAPGSYGRGTHCHYKAPTVVLHMTKTDPSLENPTHL--
NOV7g ---------------------------------------------------------
NOV7h ---------------------------------------------------------
NOV7a (SEQ ID NO: 88)
NOV7b (SEQ ID NO: 90)
NOV7c (SEQ ID NO: 92)
NOV7d (SEQ ID NO: 94)
NOV7e (SEQ ID NO: 96)
NOV7f (SEQ ID NO: 98)
NOV7g (SEQ ID NO: 100)
NOV7h (SEQ ID NO: 92)

[0418] Further analysis of the NOV7a protein yielded the following properties shown in Table 7E.

TABLE 7E
Protein Sequence Properties NOV7a
SignalP	Cleavage site between residues 23 and 24
analysis:
PSORT II	PSG: a new signal peptide prediction method
analysis:	N-region: length 7; pos. chg 1; neg. chg 0
	H-region: length 16; peak value 7.33
	PSG score: 2.93
	GvH: von Heijne's method for signal seq. recognition
	GvH score (threshold: −2.1): 0.38
	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: 8
	INTEGRAL	Likelihood =	−3.24	Transmembrane	239-255
	INTEGRAL	Likelihood =	−3.35	Transmembrane	267-283
	INTEGRAL	Likelihood =	−1.49	Transmembrane	313-329
	INTEGRAL	Likelihood =	−0.32	Transmembrane	360-376
	INTEGRAL	Likelihood =	0.32	Transmembrane	390-406
	INTEGRAL	Likelihood =	−3.35	Transmembrane	409-425
	INTEGRAL	Likelihood =	−4.67	Transmembrane	448-464
	INTEGRAL	Likelihood =	−6.32	Transmembrane	506-522
	PERIPHERAL	Likelihood =	6.84 (at 88)
	ALOM score: −6.32 (number of TMSs: 8)
	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 3a
	MITDISC: discrimination of mitochondrial targeting seq
	R content:	1	Hyd Moment (75):	5.05
	Hyd Moment (95):	6.92	G content:	3
	D/E content:	1	S/T content:	0
	Score: −5.56
	Gavel: prediction of cleavage sites for mitochondrial preseq
	R-2 motif at 17 LRG|AL
	NUCDISC: discrimination of nuclear localization signals
	pat4: none
	pat7: none
	bipartite: none
	content of basic residues: 8.8%
	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:
	Leucine zipper pattern (PS00029): *** found ***
	LVPLSGYLVLGSSFLLTGFVAL at 403
	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):
	77.8%: endoplasmic reticulum
	22.2%: mitochondrial
	>> prediction for CG55690-01 is end (k = 9)

[0419] PFam analysis predicts that the NOV7a protein contains the domains shown in the Table 7F.

TABLE 7F
Domain Analysis of NOV7a
	NOV7a Match	Identities/Similarities	Expect
Pfam Domain	Region	for the Matched Region	Value
Fz	29 . . . 153	63/151	(42%)	4.8e−67
		116/151	(77%)
7tm_2	229 . . . 473	40/297	(13%)	0.92
		143/297	(48%)
Frizzled	221 . . . 547	198/343	(58%)	1.8e−214
		315/343	(92%)

Example 8. NOV 8, CG57049, PHOSPHATIDYLETHANOLAMINE-BINDING PROTEIN.

[0420] The NOV8 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 8A.

TABLE 8A
NOV8 Sequence Analysis
NOV8a, CG57049-01	SEQ ID NO: 107	876 bp
DNA Sequence	ORF Start: ATG at 108	ORF Stop: end of sequence
TCAGGTGGCAGTCCTCCCAAAGTACTTGTGTCCGGATGGTGGACTGGATTAGCTGCGGAGCCCTGGAA
GCTGCCTTTCCTTCTCCCTGTGCTTAACCAGAGGTGCCCATGGGTTGGACAATGAGGCTGGTCACAGC
AGCACTGTTACTGGGTCTCATGATGGTGGTCACTGGAGACGAGGATGAGAACAGCCCGTGTGCCCATG
AGGCCCTCTTGGACGAGGACACCCTCTTTTGCCAGGCCCTTGAAGTTTTCTACCCAGAGTTCGGGAAC
ATTGGCTGCAAGGTTGTTCCTGATTGTAACAACTACAGACAGAAGATCACCTCCTGGATGGAGCCGAT
AGTCAAGTTCCCGGGGGCCGTGGACGGCGCAACCTATATCCTGGTGATGGTGGATCCAGATGCCCCTA
GCAGAGCAGAACCCAGACAGAGATTCTGGAGACATTGGCTGGTAACAGATATCAAGGGCGCCGACCTG
AAGAAAGGCAAGATTCAGGGCCAGGAGTTATCAGCCTACCAGGCTCCCTCCCCACCGGCACACAGTGG
CTTCCATCGCTACCAGTTCTTTGTCTATCTTCAGGAAGGAAAAGTCATCTCTCTCCTTCCCAAGGAAA
ACAAAACTCGAGGCTCTTGGAAAATGGACAGATTTCTGAACCGTTTCCACCTGGGCGAACCTGAAGCA
AGCACCCAGTTCATGACCCAGAACTACCAGGACTCACCAACCCTCCAGGCTCCCAGAGAAAGGGCCAG
CGGGCCCAAGCACAAAAACCAGGCGGAGATAGCTGCCTGCTAGATAGCCGGCTTTGCCATCCGGGCAT
GTGGCCACACTACCCACCACCGACCATGTGGGTATGGAACCCCCTCTGGATACAGAACCA
NOV8a, CG57049-01
Protein Sequence	SEQ ID NO: 108	227 aa	MW at 25661.1kD
MGWTMRLVTAALLLGLMMVVTGDEDENSPCAHEALLDEDTLFCQGLEVFYPELGNIGCKVVPDCNNYR
QKITSWMEPIVKFPGAVDGATYILVMVDPDAPSRAEPRQRFWRHWLVTDIKGADLKKGKIQGQELSAY
QAPSPPAHSGFHRYQFFVYLQEGKVISLLPKENKTRGSWKMDRFLNRFHLGEPEASTQFMTQNYQDSP
TLQAPRERASGPKHKNQAEIAAC
NOV8b, 224699879	SEQ ID NO: 109	627 bp
DNA Sequence	ORF Start: at 1	ORF Stop: end of sequence
AGATCTGACGAGGATGAGAACAGCCCGTGTGCCCATGAGGCCCTCTTGGACGAGGACACCCTCTTTTG
CCAGGGCCTTGAAGTTTTCTACCCAGAGTTGGGGAACATTGGCTGCAAGGTTGTTCCTGATTGTAACA
ACTACAGACAGAAGATCACCTCCTGGATGGAGCCGATAGTCAAGTTCCCGGGGGCCGTGGACGGCGCA
ACCTATATCCTGGTGATGGTGGATCCAGATGCCCCTAGCAGAGCAGAACCCAGACAGAGATTCTGGAG
ACATTGGGTGGTAACAGATATCAAGGGCGCCGACCTGAAGAAAGGGAAGATTCAGGGCCAGGAGTTAT
CAGCCTACCAGGCTCCCTCCCCACCGGCACACAGTGGCTTCCATCGCTACCAGTTCTTTGTCTATCTT
CAGGAAGGAAAAGTCATCTCTCTCCTTCCCAAGGAAAACAAAACTCGAGGCTCTTGGAAAATGGACAG
ATTTCTGAACCGTTTCCACCTGGGCGAACCTGAAGCAAGCACCCAGTTCATGACCCAGAACTACCAGG
ACTCACCAACCCTCCAGGCTCCCAGAGAAAGGGCCAGCGAGCCCAAGCACAAAAACCAGGCGGAGATA
GCTGCCTGCGTCGAC
NOV8b, 224699879
Protein Sequence	SEQ ID NO: 110	209 aa	MW at 23829.6kD
RSDEDENSPCAHEALLDEDTLFCQGGLEVFYPELGNIGCKVVPDCNNYRQKITSWMEPIVKFPGAVDGA
TYILVMVDPDAPSRAEPRQRFWRHWVVTDIKGADLKKGKIQGQELSAYQAPSPPAHSGFHRYQFFVYL
QEGKVISLLPKENKTRGSWKMDRFLNRFHLGEPEASTQFMTQNYQDSPTLQAPRERASEPKHKNQAEI
AACVD
NOV8c, 175069519	SEQ ID NO: 111	627 bp
DNA Sequence	ORF Start: at 1	ORF Stop: end of sequence
AGATCTGACGAGGATGAGAACAGCCCGTGTGCCCATGAGGCCCTCTTGGACGAGGACACCCTCTTTTG
CCAGGGCCTTGAAGTTTTCTACCCAGAGTTGGGGAACATTGGCTGCAAGGTTGTTCCTGATTGTAACA
ACTACAGACAGGAGATCACCCCCTGGATGGAGCCGATAGTCAAGTTCCCGGGGGCCGTGGACGGCGCA
ACCTATATCCTGGTGATGGTGGATCCAGATGCCCCTAGCAGAGCAGAACCCAGACAGAGATTCTGGAG
ACATTGGCTGGTAACAGATATCAAGGGCGCCGACCTGAAGGAAGGGAAGATTCAGGGCCAGGAGTTAT
CAGCCTACCAGGCTCCCTCCCCACCGGCACACAGTGGCTTCCATCGCTACCAGTTCTTTGTCTATCTT
CAGGAAGGAAAAGTCATCTCTCTCCTTCCCAAGGAAAACAAAACTCGAGGCTCTTGGAAAATGGACAG
ATTTCTGAACCGTTTCCACCTGGGCGAACCTGAAGCAAGCACCCAGTTCATGACCCAGAACTACCAGG
ACTCACCAACCCTCCAGGCTCCCAGAGAAAGGGCCAGCGAGCCCAAGCACAAAAACCAGGCGGAGATA
GCTGCCTGCGTCGAC
NOV8c, 175069519
Protein Sequence	SEQ ID NO: 112	209 aa	MW at 23855.6kD
RSDEDENSPCAHEALLDEDTLFCQGLEVFYPELGNIGCKVVPDCNNYRQEITPWMEPIVKFPGAVDGA
TYILVMVDPDAPSRAEPRQRFWRHWLVTDIKGADLKEGKIQGQELSAYQAPSPPAHSGFHRYQFFVYL
QEGKVISLLPKENKTRGSWKMDRFLNRFHLGEPEASTQFMTQNYQDSPTLQAPRERASEPKHKNQAEI
AACVD
NOV8d, 175069563	SEQ ID NO: 113	627 bp
DNA Sequence	ORF Start: at 1	ORF Stop: end of sequence
AGATCGGACGAGGATGAGAACAGCCCGTGTGCCCATGAGGCCCTCTTGGACGAGGACACCCTCTTTTG
CCAGGGCCTTGAAGTTTTCTACCCAGAGTTGGGGAACATTGGCTGCAAGGTTGTTCCTGATTGTAACA
ACTACAGACAGAAGATCACCTCCTGGATGGAGCCGATAGTCAAGTTCCCGGGGGCCGTGGACGGCGCA
ACCTATATCCTGGTGATGGTGGATCCAGATGCCCCTAGCAGAGCAGAACCCAGACAGAGATTCTGGAG
ACATTGGCTGGTAACAGATATCAAGGGCGCCGACCTGAAGAAAGGGAAGATTCAGGGCCAGGAGTTAT
CAGCCTACCAGGCTCCCTCCCCACCGGCACACAGTGGCTTCCATCGCTACCAGTTCTTTGTCTATCTT
CAGGAAGGAAAAGTCATCTCTCTCCTTCCCAAGCAAAACAAAACTCGAGGCTCTTGGAAAATGGACAG
ATTTCTGAACCGTTTCCACCTGGGCGAACCTGAAGCAAGCACCCAGTTCATGACCCAGAACTACCAGG
ACTCACCAACCCTCCAGGCTCCCAGAGAAAGGGCCAGCGAGCCCAAGCACAAAAACCAGGCGGAGATA
GCTGCCTGCGTCGAC
NOV8d, 175069563
Protein Sequence	SEQ ID NO: 114	209 aa	MW at 23843.6kD
RSDEDENSPCAHEALLDEDTLFCQGLEVFYPELGNIGCKVVPDCNNYRQKITSWMEPIVKFPGAVDGA
TYILVMVDPDAPSRAEPRQRFWRHWLVTDIKGADLKKGKIQGQELSAYQAPSPPAHSGFHRYQFFVYL
QEGKVISLLPKENKTRGSWKMDRFLNRFHLGEPEASTQFMTQNYQDSPTLQAPRERASEPKHKNQAEI
AACVD
NOV8e, CG57049-02	SEQ ID NO: 115	627 bp
DNA Sequence	ORF Start: at 7	ORF Stop: end of sequence
AGATCTGACGAGGATGAGAACAGCCCGTGTGCCCATGAGGCCCTCTTGGACGAGGACACCCTCTTTTG
CCAGGGCCTTGAAGTTTTCTACCCAGAGTTGGGGAACATTGGCTGCAAGGTTGTTCCTGATTGTAACA
ACTACAGACAGGAGATCACCCCCTGGATGGAGCCGATAGTCAAGTTCCCGGGGGCCGTGGACGGCGCA
ACCTATATCCTGGTGATGGTGGATCCAGATGCCCCTAGCAGAGCAGAACCCAGACAGAGATTCTGGAG
ACATTGGCTGGTAACAGATATCAAGGGCGCCGACCTGAAGGAAGGGAAGATTCAGGGCCAGGAGTTAT
CAGCCTACCAGGCTCCCTCCCCACCGGCACACAGTGGCTTCCATCGCTACCAGTTCTTTGTCTATCTT
CAGGAAGGAAAAGTCATCTCTCTCCTTCCCAAGGAAAACAAAACTCGAGGCTCTTGCAAAATGGACAG
ATTTCTGAACCGTTTCCACCTGGGCGAACCTGAAGCAAGCACCCAGTTCATGACCCAGAACTACCAGG
ACTCACCAACCCTCCAGGCTCCCAGAGAAAGGGCCAGCGAGCCCAAGCACAAAAACCAGGCGGAGATA
GCTGCCTGCGTCGAC
NOV8e, CG57049-02
Protein Sequence	SEQ ID NO: 116	205 aa	MW at 23398.1kD
DEDENSPCAHEALLDEDTLFCQGLEVFYPELGNIGCKVVPDCNNYRQEITPWMEPIVKFPGAVDGATY
ILVMVDPDAPSRAEPRQRFWRHWLVTDIKGADLKEGKIQGQELSAYQAPSPPAHSGFHRYQFFVYLQE
GKVISLLPKENKTRGSWKMDRFLNRFHLGEPEASTQFMTQNYQDSPTLQAPRERASEPKHKNQAEIAA
C
NOV8f, 13379525	SEQ ID NO: 117	876 bp
DNA Sequence	ORF Start: ATG at 108	ORF Stop: end of sequence
TCAGGTGCCAGTCCTCCCAAAGTACTTGTGTCCGGATGGTGGACTGGATTAGCTGCGGAGCCCTGGAA
GCTGCCTTTCCTTCTCCCTGTGCTTAACCAGAGGTGCCCATGGGTTGGACAATGAGGCTGGTCACAGC
AGCACTGTTACTGGCTCTCATGATGGTGGTCGCTGGAGACGAGGATGAGAACAGCCCGTGTGCCCATG
AGGCCCTCTTGGACGAGGACACCCTCTTTTGCCAGGGCCTTGAAGTTTTCTACCCAGAGTTGGGGAAC
ATTGGCTGCAAGGTTGTTCCTGATTGTAACAACTACAGACAGAAGATCACCTCCTGGATGGAGCCGAT
AGTCAAGTTCCCGGGGGCCGTGGACGGCGCAACCTATATCCTGGTGATGGTGGATCCAGATGCCCCTA
GCAGAGCAGAACCCAGACAGAGATTCTGGAGACATTGGCTGGTAACAGATATCAAGGGCGCCGACCTG
AAGAAAGGGAAGATTCAGGGCCAGGAGTTATCAGCCTACCAGGCTCCCTCCCCACCGGCACACAGTGG
CTTCCATCGCTACCAGTTCTTTGTCTATCTTCAGGAAGGAAAAGTCATCTCTCTCCTTCCCAAGGAAA
ACAAAACTCGAGGCTCTTGGAAAATGGACAGATTTCTGAACCGTTTCCACCTGGGCGAACCTGAAGCA
AGCACCCAGTTCATGACCCAGAACTACCAGGACTCACCAACCCTCCAGGCTCCCAGAGAAAGGGCCAG
CGGGCCCAAGCACAAAAACCAGGCGGAGATAGCTGCCTGCTAGATAGCCGGCTTTGCCATCCGGGCAT
GTGGCCACACTACCCACCACCGACGATGTGGGTATGGAACCCCCTCTGGATACAGAACCA
NOV8f, 13379525
Protein Sequence	SEQ ID NO: 118	227 aa	MW at 25661.1kD
MGWTMRLVTAALLLGLMMVVAGDEDENSPCAHEALLDEDTLFCQGLEVFYPELGNIGCKVVPDCNNYR
QKITSWMEPIVKFPGAVDGATYILVMVDPDAPSRAEPRQRFWRHWLVTDIKGADLKKGKIQGQELSAY
QAPSPPAHSGFHRYQFFVYLQEGKVISLLPKENKTRGSWKMDRFLNRFHLGEPEASTQFMTQNYQDSP
TLQAPRERASGPKHKNQAEIAAC
NOV8g, 13379526	SEQ ID NO: 119	876 bp
DNA Sequence	ORF Start: ATG at 108	ORF Stop: end of sequence
TCAGGTGGCAGTCCTCCCAAAGTACTTGTGTCCGGATGGTGGACTGGATTAGCTGCGGAGCCCTGGAA
GCTGCCTTTCCTTCTCCCTGTGCTTAACCAGAGGTGCCCATGGGTTGGACAATGAGGCTGGTCACAGC
AGCACTGTTACTGGGTCTCATGATGGTGGTCACTGGAGACGAGGATGAGAACAGCCCGTGTGCCCATG
AGGCCCCCTTGGACGAGGACACCCTCTTTTGCCAGGGCCTTGAAGTTTTCTACCCAGAGTTGGGGAAC
ATTGGCTGCAAGGTTGTTCCTGATTGTAACAACTACAGACAGAAGATCACCTCCTGGATGGAGCCGAT
AGTCAAGTTCCCGGGGGCCGTGGACGGCGCAACCTATATCCTGGTGATGGTGGATCCAGATGCCCCTA
GCAGAGCAGAACCCAGACAGAGATTCTGGAGACATTGGCTGGTAACAGATATCAAGGGCGCCGACCTG
AAGAAAGGGAAGATTCAGGGCCAGGAGTTATCAGCCTACCAGGCTCCCTCCCCACCGGCACACAGTGG
CTTCCATCGCTACCAGTTCTTTGTCTATCTTCAGGAAGGAAAAGTCATCTCTCTCCTTCCCAAGGAAA
ACAAAACTCGAGGCTCTTGGAAAATGGACAGATTTCTGAACCGTTTCCACCTGGGCGAACCTGAAGCA
AGCACCCAGTTCATGACCCAGAACTACCAGGACTCACCAACCCTCCAGGCTCCCAGAGAAAGGGCCAG
CGGGCCCAAGCACAAAAACCAGGCGGAGATAGCTGCCTGCTAGATAGCCCGCTTTGCCATCCGGGCAT
GTGGCCACACTACCCACCACCGACGATGTGGGTATGGAACCCCCTCTGGATACAGAACCA
NOV8g, 13379526
Protein Sequence	SEQ ID NO: 120	227 aa	MW at 25661.1kD
MGWTMRLVTAALLLGLMMVVTGDEDENSPCAHEAPLDEDTLFCQGLEVFYPELGNIGCKVVPDCNNYR
QKITSWMEPIVKFPGAVDGATYILVMVDPDAPSRAEPRQRFWRHWLVTDIKGADLKKGKIQGQELSAY
QAPSPPAHSGFHRYQFFVYLQEGKVISLLPKENKTRGSWKMDRFLNRFHLGEPEASTQFMTQNYQDSP
TLQAPRERASGPKHKNQAEIAAC
NOV8h, 13373853	SEQ ID NO: 121	876 bp
DNA Sequence	ORF Start: ATG at 108	ORF Stop: end of sequence
TCAGGTGGCAGTCCTCCCAAAGTACTTGTGTCCGGATGGTGGACTGGATTAGCTGCGGAGCCCTGGAA
GCTGCCTTTCCTTCTCCCTGTGCTTAACCAGAGGTGCCCATGGGTTGGACAATGAGGCTGGTCACAGC
AGCACTGTTACTGGGTCTCATGATGGTGGTCACTGGAGACGAGGATGAGAACAGCCCGTGTGCCCATG
AGGCCCTCTTGGACGAGGACACCCTCTTTTGCCAGGGCCTTGAAGTTTTCTACCCAGAGTTGGGGAAC
ATTGGCTGCAAGGTTGTTCCTGATTGTAACAACTACAGACAGAAGATCACCTCCTGGATGGAGCCGAT
AGTCAAGTTCCCGGGGGCCGTGGACGGCGCAACCTATATCCTGGTGATGGTGGATCCAGATGCCCCTA
GCAGAGCAGAACCTAGACAGAGATTCTGGAGACATTGGCTGGTAACAGATATCAAGGGCGCCGACCTG
AAGAAAGGGAAGATTCAGGGCCAGGAGTTATCAGCCTACCAGGCTCCCTCCCCACCGGCACACAGTGG
CTTCCATCGCTACCAGTTCTTTGTCTATCTTCAGGAAGGAAAAGTCATCTCTCTCCTTCCCAAGGAAA
ACAAAACTCGAGGCTCTTGGAAAATGGACAGATTTCTGAACCGTTTCCACCTGGGCGAACCTGAAGCA
AGCACCCAGTTCATGACCCAGAACTACCAGGACTCACCAACCCTCCAGGCTCCCAGAGAAAGGGCCAG
CGGGCCCAAGCACAAAAACCAGGCGGAGATAGCTGCCTGCTAGATAGCCGGCTTTGCCATCCGGGCAT
GTGGCCACACTACCCACCACCGACGATGTGGGTATGGAACCCCCTCTGGATACAGAACCA
NOV8h, 13373853
Protein Sequence	SEQ ID NO: 122	227 aa	MW at 25661.1kD
MGWTMRLVTAALLLGLMMVVTGDEDENSPCAHEALLDEDTLFCQGLEVFYPELGNIGCKVVPDCNNYR
QKITSWMEPIVKFPGAVDGATYILVMVDPDAPSRAELRQRFWRHWLVTDIKGADLKKGKIQGQELSAY
QAPSPPAHSGFHRYQFFVYLQEGKVISLLPKENKTRGSWKMDRFLNRFHLGEPEASTQFMTQNYQDSP
TLQAPRERASGPKHKNQAEIAAC
NOV8i, 13373737	SEQ ID NO: 123	876 bp
DNA Sequence	ORF Start: ATG at 108	ORF Stop: end of sequence
TCAGGTGGCAGTCCTCCCAAAGTACTTGTGTCCGGATGGTGGACTGGATTAGCTGCGGAGCCCTGGAA
GCTGCCTTTCCTTCTCCCTGTGCTTAACCAGACGTGCCCATGGGTTGGACAATGAGGCTGGTCACAGC
AGCACTGTTACTGGGTCTCATGATGGTGGTCACTGGAGACGAGGATGAGAACAGCCCGTGTGCCCATG
ACGCCCTCTTGGACGAGGACACCCTCTTTTGCCAGGGCCTTGAAGTTTTCTACCCAGAGTTGGGGAAC
ATTGGCTGCAAGGTTGTTCCTGATTGTAACAACTACAGACAGAAGATCACCTCCTGGATGGAGCCGAT
AGTCAAGTTCCCGGGGGCCGTGGACGGCGCAACCTATATCCTGGTGATGGTGGATCCAGATGCCCCTA
GCAGAGCACAACCCAGACAGACATTCTGGAGACATTGGCTGGTAACAGATATCAAGGGCGCCGACCTG
AAGGAAGGGAAGATTCAGGGCCAGGAGTTATCAGCCTACCAGGCTCCCTCCCCACCGGCACACAGTGG
CTTCCATCGCTACCAGTTCTTTGTCTATCTTCAGGAAGGAAAAGTCATCTCTCTCCTTCCCAAGGAAA
ACAAAACTCGAGGCTCTTGGAAAATGGACAGATTTCTGAACCGTTTCCACCTGGGCGAACCTGAAGCA
AGCACCCAGTTCATGACCCAGAACTACCAGGACTCACCAACCCTCCAGGCTCCCAGAGAAAGGGCCAG
CGGGCCCAAGCACAAAAACCAGGCGGAGATAGCTGCCTGCTAGATAGCCGGCTTTGCCATCCGGGCAT
GTGGCCACACTACCCACCACCGACGATGTGGGTATGGAACCCCCTCTGGATACAGAACCA
NOV8i, 13373737
Protein Sequence	SEQ ID NO: 124	227 aa	MW at 25661.1kD
MGWTMRLVTAALLLGLMMVVTGDEDENSPCAHEALLDEDTLFCQGLEVFYPELGNIGCKVVPDCNNYR
QKITSWMEPIVKFPGAVDGATYILVMVDPDAPSRAEPRQRFWRHWLVTDIKGADLKEGKIQGQELSAY
QAPSPPAHSGFHRYQFFVYLQEGKVISLLPKENKTRGSWKMDRFLNRFHLGEPEASTQFMTQNYQDSP
TLQAPRERASGPKHKNQAEIAAC
NOV8j, 13376382	SEQ ID NO: 125	876 bp
DNA Sequence	ORF Start: ATG at 108	ORF Stop: end of sequence
TCAGGTGGCAGTCCTCCCAAAGTACTTGTGTCCGGATGGTGGACTGGATTAGCTGCGGAGCCCTGGAA
GCTGCCTTTCCTTCTCCCTGTGCTTAACCAGAGGTGCCCATGGGTTGGACAATGAGGCTGGTCACAGC
AGCACTGTTACTGGGTCTCATGATGGTGGTCACTGGAGACGAGGATGAGAACAGCCCGTGTGCCCATG
AGGCCCTCTTGGACGAGGACACCCTCTTTTGCCAGGGCCTTGAAGTTTTCTACCCAGAGTTGGGGAAC
ATTGGCTGCAAGGTTGTTCCTGATTGTAACAACTACAGACAGAAGATCACCTCCTGGATGGAGCCGAT
AGTCAAGTTCCCGGGGGCCGTGGACGGCGCAACCTATATCCTGGTGATGGTGGATCCAGATGCCCCTA
GCAGAGCAGAACCCAGACAGAGATTCTGGAGACATTGGCTGGTAACAGATATCAAGGGCGCCGACCTG
AAGAAAGGGAAGATTCAGGGCCAGGACTTATCAGCCTACCAGGCTCCCTCCCCACCGGCACACAGTGG
CTTCCATCGCTACCAGTTCTTTGTCTATCTTCAGGAACGAAGAGTCATCTCTCTCCTTCCCAAGGAAA
ACAAAACTCGAGCCTCTTGGAAAATGGACAGATTTCTCAACCGTTTCCACCTGGGCGAACCTGAAGCA
AGCACCCAGTTCATGACCCAGAACTACCAGGACTCACCAACCCTCCAGGCTCCCAGAGAAAGGGCCAG
CGGGCCCAAGCACAAAAACCAGGCGGACATAGCTGCCTGCTAGATAGCCGGCTTTGCCATCCGGGCAT
GTGGCCACACTACCCACCACCGACGATGTGGGTATGGAACCCCCTCTGGATACAGAACCA
NOV8j, 1337638
Protein Sequence	SEQ ID NO: 126	277 aa	MW at 25661.1kD
MGWTMRLVTAALLLGLMMVVTGDEDENSPCAHEALLDEDTLFCQGLEVFYPELGNIGCKVVPDCNNYR
QKITSWMEPIVKFPGAVDGATYILVMVDPDAPSRAEPRQRFWRHWLVTDIKGADLKKGKIQGQELSAY
QAPSPPAHSGFHRYQFFVYLQEGRVISLLPKENKTRGSWKMDRFLNRFHLGEPEASTQFMTQNYQDSP
TLQAPRERASGPKHKNQAEIAAC
NOV8k, 13373850	SEQ ID NO: 127	876 bp
DNA Sequence	ORF Start: ATG at 108	ORF Stop: end of sequence
TCAGGTGGCAGTCCTCCCAAAGTACTTGTGTCCGGATGGTGGACTGGATTAGCTGCGGAGCCCTGGAA
GCTGCCTTTCCTTCTCCCTGTGCTTAACCAGAGGTGCCCATGGGTTGGACAATGAGGCTGGTCACAGC
AGCACTGTTACTGGGTCTCATGATGGTGGTCACTGGAGACGAGGATGAGAACAGCCCGTGTGCCCATG
ATTGGCTGCAAGGTTGTTCCTGATTGTAACAACTACAGACAGAAGATCACCTCCTGGATGGAGCCGAT
AGTCAAGTTCCCGGGGGCCGTGGACGGCGCAACCTATATCCTGGTGATGGTGGATCCAGATGCCCCTA
GCAGAGCAGAACCCAGACAGAGATTCTGGAGACATTGGCTGGTAACAGATATCAAGGGCGCCGACCTG
AAGAAAGGGAAGATTCAGGGCCAGGAGTTATCAGCCTACCAGGCTCCCTCCCCACCGGCACACAGTGG
CTTCCATCGCTACCAGTTCTTTGTCTATCTTCAGGAAGGAAAAGTCATCTCTCTCCTTCCCAAGGAAA
ACAAAACTCGAGGCTCTTGGAAAATGGACACATTTCTGAACCGTTTCCACCTGGGCGAACCTGAAGCA
AGCACCCAGTTCATGACCCAGAACTACCAGGACTCACCAACCCTCCAGGCTCCCAGAGGAAGGGCCAG
CGGGCCCAAGCACAAAAACCAGGCGGAGATAGCTGCCTGCTAGATAGCCGGCTTTGCCATCCGGGCAT
GTGGCCACACTACCCACCACCGACGATGTGGGTATGGAACCCCCTCTGGATACAGAACCA
NOV8k, 13373850
Protein Sequence	SEQ ID NO: 128	227 aa	MW at 25661.1kD
MGWTMRLVTAALLLGLMMVVTGDEDENSPCAHEALLDEDTLFCQGLEVFYPELGNIGCKVVPDCNNYR
QKITSWMEPIVKFPGAVDGATYILVMVDPDAPSRAEPRQRFWRHWLVTDIKGADLKKGKIQGQELSAY
QAPSPPAHSGFHRYQFFVYLQEGKVISLLPKENKTRGSWKMDRFLNRFHLGEPEASTQFMTQNYQDSP
TLQAPRGRASGPKHKNQAEIAAC
NOV8l, 13373849	SEQ ID NO: 129	876 bp
DNA Sequence	ORF Start: ATG at 108	ORF Stop: end of sequence
TCAGGTGGCAGTCCTCCCAAAGTACTTGTGTCCGGATGGTGGACTGGATTAGCTGCGGAGCCCTGGAA
GCTGCCTTTCCTTCTCCCTGTGCTTAACCAGAGGTGCCCATGGGTTGGACAATGAGGCTGGTCACAGC
AGCACTGTTACTGGGTCTCATGATCGTGGTCACTGGAGACGAGGATGAGAACAGCCCGTGTGCCCATG
AGGCCCTCTTGGACGAGGACACCCTCTTTTGCCAGGGCCTTGAAGTTTTCTACCCAGAGTTGGGGAAC
ATTGGCTGCAAGGTTGTTCCTGATTGTAACAACTACAGACAGAAGATCACCTCCTGGATGGAGCCGAT
AGTCAAGTTCCCGGCGGCCGTGGACGGCGCAACCTATATCCTGGTGATGGTGGATCCAGATGCCCCTA
GCAGAGCAGAACCCAGACAGAGATTCTGGAGACATTGGCTGGTAACAGATATCAAGGGCGCCGACCTG
AAGAAAGGGAAGATTCAGGGCCAGGAGTTATCAGCCTACCAGGCTCCCTCCCCACCGGCACACAGTGG
CTTCCATCGCTACCAGTTCTTTGTCTATCTTCAGGAAGGAAAAGTCATCTCTCTCCTTCCCAAGGAAA
ACAAAACTCGAGGCTCTTGGAAAATGGACAGATTTCTGAACCGTTTCCACCTGGGCGAACCTGAAGCA
AGCACCCAGTTCATCACCCAGAACTACCAGGACTCACCAACCCTCCAGGCTCCCAGAGAAAGGGCCAG
CGAGCCCAAGCACAAAAACCAGGCGGAGATAGCTGCCTGCTAGATAGCCGGCTTTGCCATCCCGGCAT
GTGGCCACACTACCCACCACCGACGATGTGGGTATGGAACCCCCTCTGGATACAGAACCA
NOV8l,
Protein Sequence	SEQ ID NO: 130	227 aa	MW at 25661.1kD
MGWTMRLVTAALLLGLMMVVTGDEDENSPCAHEALLDEDTLFCQGLEVFYPELGNIGCKVVPDCNNYR
QKITSWMEPIVKFPGAVDGATYILVMVDPDAPSRAEPRQRFWRHWLVTDIKGADLKKGKIQGQELSAY
QAPSPPAHSGFHRYQFFVYLQEGKVISLLPKENKTRGSWKMDRFLNRFHLGEPEASTQFMTQNYQDSP
TLQAPRERASQPKHKNQAEIAAC

[0421] A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 8B.

TABLE 8B
Comparison of the NOV8 protein sequences.
NOV8a MGWTMRLVTAALLLGLMMVVTGDEDENSPCAHEALLDEDTLFCQGLEVFYPELGNIGCKV
NOV8b --------------------RSDEDENSPCAHEALLDEDTLFCQGLEVFYPELGNIGCKV
NOV8c --------------------RSDEDENSPCAHEALLDEDTLFCQGLEVFYPELGNIGCKV
NOV8d --------------------RSDEDENSPCAHEALLDEDTLFCQGLEVFYPELGNIGCKV
NOV8e ----------------------DEDENSPCAHEALLDEDTLFCQGLEVFYPELGNIGCKV
NOV8a VPDCNNYRQKITSWMEPIVKFPGAVDGATYILVMVDPDAPSRAEPRQRFWRHWLVTDIKG
NOV8b VPDCNNYRQKITSWMEPIVKFPGAVDGATYILVMVDPDAPSRAEPRQRFWRHWVVTDIKG
NOV8c VPDCNNYRQEITPWMEPIVKFPGAVDGATYILVMVDPDAPSRAEPRQRFWRHWLVTDIKG
NOV8d VPDCNNYRQKITSWMEPIVKFPGAVDGATYILVMVDPDAPSRAEPRQRFWRHWLVTDIKG
NOV8e VPDCNNYRQEITPWMEPIVKFPGAVDGATYILVMVDPDAPSRAEPRQRFWRHWLVTDIKG
NOV8a ADLKKGKIQGQELSAYQAPSPPAHSGFHRYQFFVYLQEGKVISLLPKENKTRGSWKMDRF
NOV8b ADLKKGKIQGQELSAYQAPSPPAHSGFHRYQFFVYLQEGKVISLLPKENKTRGSWKMDRF
NOV8c ADLKEGKIQGQELSAYQAPSPPAHSGFHRYQFFVYLQEGKVISLLPKENKTRGSWKMDRF
NOV8d ADLKKGKIQGQELSAYQAPSPPAHSGFHRYQFFVYLQEGKVISLLPKENKTRGSWKMDRF
NOV8e ADLKEGKIQGQELSAYQAPSPPAHSGFHRYQFFVYLQEGKVISLLPKENKTRGSWKMDRF
NOV8a LNRFHLGEPEASTQFMTQNYQDSPTLQAPRERASGPKHKNQAEIAAC--
NOV8b LNRFHLGEPEASTQFMTQNYQDSPTLQAPRERASEPKHKNQAEIAACVD
NOV8c LNRFHLGEPEASTQFMTQNYQDSPTLQAPRERASEPKHKNQAEIAACVD
NOV8d LNRFHLGEPEASTQFMTQNYQDSPTLQAPRERASEPKHKNQAEIAACVD
NOV8e LNRFHLGEPEASTQFMTQNYQDSPTLQAPRERASEPKNKNQAEIAAC--
NOV8a (SEQ ID NO: 108)
NOV8b (SEQ ID NO: 110)
NOV8c (SEQ ID NO: 112)
NOV8d (SEQ ID NO: 114)
NOV8e (SEQ ID NO: 116)

[0422] Further analysis of the NOV8a protein yielded the following properties shown in Table 8C.

TABLE 8C
Protein Sequence Properties NOV8
SignalP	Cleavage site between residues 23 and 24
analysis:
PSORT II	PSG: a new signal peptide prediction method
analysis:	N-region: length 6; pos. chg 1; neg. chg 0
	H-region: length 16; peak value 11.29
	PSG score: 6.89
	GvH: von Heijne's method for signal seq. recognition
	GvH score (threshold: −2.1): 1.04
	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: 0
	number of TMS(s) . . . fixed
	PERIPHERAL Likelihood = 2.65 (at 78)
	ALOM score: 2.65 (number of TMSs: 0)
	MTOP: Prediction of membrane topology (Hartmann et al.)
	Center position for calculation: 11
	Charge difference: −7.5 C(−5.5)-N(2.0)
	N >= C: N-terminal side will be inside
	MITDISC: discrimination of mitochondrial targeting seq
	R content:	1	Hyd Moment(75):	6.09
	Hyd Moment(95):	8.77	G content:	3
	D/E content:	1	S/T content:	3
	Score:	−4.30
	Gavel: prediction of cleavage sites for mitochondrial preseq
	R-2 motif at 16 MRL|VT
	NUCDISC: discrimination of nuclear localization signals
	pat4: none
	pat7: none
	bipartite: none
	content of basic residues: 11.0%
	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%: mitochondrial
	22.2%: endoplasmic reticulum
	11.1%: Golgi
	11.1%: vacuolar
	>> prediction for CG57049-01 is exc (k = 9)

[0423] 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
Geneseq	Protein/Organism/Length	Match	for the	Expect
Identifier	[Patent #, Date]	Residues	Matched Region	Value
AAB88590	Human hydrophobic domain	1 . . . 227	226/227 (99%)	e−134
	containing protein clone HP03880	1 . . . 227	226/227 (99%)
	#94 - Homo sapiens, 227 aa.
	[WO200112660-A2, 22 Feb. 2001]
AAY64647	Human phosphatidylethanolamine-	1 . . . 227	226/227 (99%)	e−134
	binding protein - Homo sapiens, 227	1 . . . 227	226/227 (99%)
	aa. [WO9953051-A2, 21 Oct.
	1999]
AAG00016	Human secreted protein #4 - Homo	1 . . . 227	226/227 (99%)	e−134
	sapiens, 227 aa. [EP1033401-A2,	1 . . . 227	226/227 (99%)
	6 Sep. 2000]
AAY35976	Extended human secreted protein	1 . . . 227	226/227 (99%)	e−134
	sequence, SEQ ID NO. 225 - Homo	1 . . . 227	226/227 (99%)
	sapiens, 227 aa. [WO9931236-A2,
	24 Jun. 1999]
AAB48368	Human SEC1 protein sequence	1 . . . 227	225/227 (99%)	e−134
	(clone ID 3445452) - Homo sapiens,	1 . . . 227	226/227 (99%)
	227 aa. [WO200078802-A2, 28
	Dec. 2000]

[0424] In a BLAST search of public sequence databases, the NOV8a protein was found to have homology to the proteins shown in the BLASTP data in Table 8E.

TABLE 8E
Public BLASTP Results for NOV8a
		NOV8a	Identities/
Protein		Residues/	Similarities
Accession		Match	for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
CAC33305	Sequence 114 from Patent	1 . . . 227	226/227	(99%)	e−134
	WO0112660 - Homo sapiens	1 . . . 227	226/227	(99%)
	(Human), 227 aa.
Q96S96	Phosphatidylethanolamine binding	1 . . . 227	225/227	(99%)	e−133
	protein - Homo sapiens (Human),	1 . . . 227	226/227	(99%)
	227 aa.
Q8WW74	Hypothetical protein - Homo	1 . . . 221	216/221	(97%)	e−128
	sapiens (Human), 223 aa.	1 . . . 221	218/221	(97%)
Q9D9G2	1700081D17Rik protein - Mus	5 . . . 198	104/209	(49%)	1e−54
	musculus (Mouse), 242 aa.	12 . . . 220	132/209	(62%)
AAO39754	Putative antennal carrier protein	44 . . . 208	58/171	(33%)	3e−20
	A5 - Anopheles gambiae (African	48 . . . 205	84/171	(48%)
	malaria mosquito), 211 aa.

[0425] PFam analysis predicts that the NOV8a protein contains the domains shown in the Table 8F.

TABLE 8F
Domain Analysis of NOV8a
Pfam	NOV8a Match		Identities/Similarities	Expect
Domain	Region		for the Matched Region	Value
PBP	60 . . . 98	51/202	(25%)	2.8e−14
		101/202	(50%)

Example 9. NOV 9, CG59538 BUTYROPHILIN

[0426] The NOV9 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 9A.

TABLE 9A
NOV9 Sequence Analysis
NOV9a, CG59538-01	SEQ ID NO: 131	2659 bp
DNA Sequence	ORF Start: ATG at 62	ORF Stop: end of sequence
AGCTGTCAGCCCCCTCACAGGAAGATGCTGCGTCGCCGGGCCAGCCCTGGCATGGGTGTGCATGTGGG
TGCAGCCCTGGGAGCACTGTGGTTCTGCCTCACAGGAGCCCTGGAGGTCCAGGTCCCCTGAGGACCCG
GTGGTGGCCCTAGTGGGCACCCATGCCACCCTGCGCTGCTCCTTCTCCCCCGAGCCTGGCTTCAGCCT
GGCACAGCTCAACCTCATCTGGCAGCTGACAGACACCAAACAGCTGGTGCACAGTTTCACCGAAGGCC
GGGACCAGGGCACCGCCTATGCCAACCGCACGGCCCTCTTCCCGCACCTGCTGGCACAAGGCAATGCA
TCCCTGAGGCTGCAGCGCGTGCGTGTGGCGGACGACGGCAGCTTCACCTGCTTCGTGAGCATCCGGCA
TTTCGGCAGCGCTGCCGTCAGCCTGCAGGTGGCCGCTCCCTACTCGAAGCCCAGCATGACCCTGGAGC
CCAACAAGGACCTGCGGCCAGGGGACACGGTGACCATCACGTGCTCCAGCTACCAGGGCTACCCTGAG
GCTGAGGTGTTCTGGCAGGATGGGCAGCGTGTGCCCCTGACTGGCAACGTCACCACGTCGCAGATGGC
CAACGAGCAGGGCTTGTTTGATGTGCACACCATCCTGCGGGTGGTGCTGGGTGCAAATGGCACCTACA
GCTCCCTGGTGCCCAACCCCGTGCTGCAGCAGGATGCGCACAGCTCTGTCACCATCACACCCCAGAGA
AGCCCCACAGGAGCCGTGGAGGTCCAGGTCCCTGAGGACCCGGTGGTGGCCCTAGTGGGCACCGATGC
CACCCTGCGCTGCTCCTTCTCCCCCCAGCCTGGCTTCAGCCTCGCACAGCTCAACCTCATCTGGCAGC
TGACAGACACCAAACAGCTGGTGCACAGTTTCACCGAAGGCCGGGACCAGGGCAGCGCCTATGCCAAC
CGCACGGCCCTCTTCCCGGACCTGCTGGCACAAGGCAATGCATCCCTGAGGCTGCAGCCCGTGCGTGT
CGCGGACGAGGGCAGCTTCACCTGCTTCGTGAGCATCCGGGATTTCGGCAGCGCTCCCGTCAGCCTGC
AGGTGGCCGCTCCCTACTCGAAGCCCAGCATGACCCTGGAGCCCAACAAGGACCTGCGGCCAGGGGAC
ACGGTGACCATCACGTGCTCCAGCTACCGGGGCTACCCTGAGGCTGAGGTGTTCTGGCAGGATGGGCA
GGGTGTGCCCCTGACTGGCAACGTGACCACGTCGCAGATGGCCAACGAGCAGGGCTTGTTTGATGTGC
ACAGCGTCCTGCGGGTGGTGCTGGGTGCGAATGGCACCTACAGCTGCCTGGTGCGCAACCCCGTGCTG
CAGCAGGATGCGCACGGCTCTGTCACCATCACAGGGCAGCCTATGACATTCCCCCCAGAGGCCCTGTG
GGTGACCGTGGGGCTGTCTGTCTGTCTCATTGCACTGCTGGTGGCCCTGGCTTTCGTGTGCTGGAGAA
AGATCAAACAGAGCTGTGAGGAGGAGAATGCAGGAGCTGAGGACCAGGATGGGGAGGGAGAAGGCTCC
AAGACAGCCCTGCAGCCTCTGAAACACTCTGACAGCAAAGAAGATGATGGACAAGAAATAGCCTGACC
ATGAGGACCAGGGAGCTGCTACCCCTCCCTACAGCTCCTACCCTCTGGCTGCAATGGGGCTGCACTGT
GAGCCCTGCCCCCAACAGATGCATCCTGCTCTGACAGGTGGGCTCCTTCTCCAAAGGATGCGATACAC
AGACCACTGTGCAGCCTTATTTCTCCAATGGACATGATTCCCAAGTCATCCTGCTGCCTTTTTTCTTA
TAGACACAATGAACAGACCACCCACAACCTTAGTTCTCTAAGTCATCCTGCCTGCTGCCTTATTTCAC
AGTACATACATTTCTTAGGGACACAGTACACTGACCACATCACCACCCTCTTCTTCCAGTGCTGCGTG
GACCATCTGGCTGCCTTTTTTCTCCAAAAGATGCAATATTCAGACTGACTGACCCCCTGCCTTATTTC
ACCAAAGACACGATGCATAGTCACCCCGGCCTTGTTTCTCCAATGGCCGTGATACACTAGTGATCATG
TTCACCCCTGCTTCCACCTGCATAGAATCTTTTCTTCTCAGACAGGGACAGTGCGGCCTCAACATCTC
CTGGGGTCTAGAAGCTGTTTCCTTTCCCCTCCTTCCTCCTCTTGCTCTAGCCTTAATACTGGCCTTTT
CCCTCCCTGCCCCAAGTGAAGACAGGGCACTCTGCGCCCACCACATGCACAGCTGTGCATGGAGACCT
GCAGGTGCACGTGCTGGAACACGTGTGGTTCCCCCCTCGCCCAGCCTCCTCTGCAGTGCCCCTCTCCC
CTGCCCATCCTCCCCACGGAAGCATGTGCTGGTCACACTGGTTCTCCAGGGGTCTGTGATGGGGCCCC
TGGGGGTCAGCTTCTGTCCCTCTGCCTTCTCACCTCTTTGTTCCTTTCTTTTCATGTATCCATTCAGT
TGATGTTTATTGAGCAACTACAGATGTCAGCACTGTGTTAGGTGCTGGGGGCCCTGCGTGGGAAGATA
AAGTTCCTCCCTCAAGGACTCCCCATCCAGCTGGGAGACAGACAACTAACTACACTGCACCCTGCG
NOV9a, CG59538-01
Protein Sequence	SEQ ID NO: 132	522 aa	MW at 56436.7kD
MWVQPWEHCGSASQEPWRSRSPEDPVVALVGTDATLRCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFT
EGRDQGSAYANRTALFPDLLAQGNASLRLQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPYSKPSMT
LEPNKDLRPGDTVTITCSSYQGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLFDVHSILRVVLGANG
TYSCLVRNPVLQQDAHSSVTITPQRSPTGAVEVQVPEDPVVALVGTDATLRCSFSPEPGFSLAQLNLI
WQLTDTKQLVHSFTEGRDQGSAYANRTALFPDLLAQGNASLRLQRVRVADEGSFTCFVSIRDFGSAAV
SLQVAAPYSKPSMTLEPNKDLRPGDTVTITCSSYRGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLF
DVHSVLRVVLGANGTYSCLVRNPVLQQDAHGSVTITGQPMTFPPEALWVTVGLSVCLIALLVALAFVC
WRKIKQSCEEENAGAEDQDGEGEGSKTALQPLKHSDSKEDDGQEIA
NOV9b, CG59538-02	SEQ ID NO: 133	2880 bp
DNA Sequence	ORF Start: ATG at 40	ORF Stop: end of sequence
GTCAGCCTGCAGGTGGCCGCTCCCTACTCGAAGCCCAGCATGACCCTGGAGCCCAACAAGGACCTGCG
GCCAGGGGACACGGTGACCATCACGTGCTCCAGCTACCAGGGCTACCCTGAGGCTGAGGTGTTCTGGC
AGGATGGGCAGGGTGTGCCCCTGACTGGCAACGTGACCACGTCGCAGATGGCCAACCAGCAGGGCTTG
TTTGATGTGCACAGCATCCTGCGGGTGGTGCTGGGTGCAAATGGCACCTACAGCTGCCTGGTGCGCAA
CCCCGTGCTGCAGCAGGATGCGCACAGCTCTGTCACCATCACACCCCAGAGAAGCCCCACAGGAGCCG
TGGAGGTCCAGGTCCCTGAGGACCCGGTGGTGGCCCTAGTGGGCACCGATGCCACCCTGCGCTGCTCC
TTCTCCCCCGAGCCTGGCTTCAGCCTGCCACAGCTCAACCTCATCTGGCAGCTGACAGACACCAAACA
GCTGGTGCACAGTTTCACCGAAGGCCGGGACCAGGGCAGCGCCTATGCCAACCGCACGGCCCTCTTCC
CGGACCTGCTGGCACAAGGCAATGCATCCCTGAGGCTGCAGCGCGTGCGTGTGGCGGACGAGGGCAGC
TTCACCTGCTTCGTGAGCATCCGGGATTTCGGCAGCGCTGCCGTCAGCCTGCAGGTGGCCGCTCCCTA
CTCGAAGCCCAGCATGACCCTGGAGCCCAACAAGGACCTGCGGCCAGGGGACACGGTGACCATCACGT
GCTCCAGCTACCAGGGCTACCCTGAGGCTGAGGTGTTCTGGCAGGATGGGCAGGGTGTGCCCCTGACT
GGCAACGTGACCACGTCGCAGATGGCCAACGAGCAGGGCTTGTTTGATGTGCACAGCATCCTGCGGGT
GGTGCTGGGTCCAAATGGCACCTACAGCTGCCTGGTGCGCAACCCCGTGCTGCAGCAGGATGCGCACA
GCTCTGTCACCATCACACCCCAGAGAAGCCCCACAGGAGCCGTGGAGGTCCAGGTCCCTGAGGACCCG
GTGGTGGCCCTAGTGGCCACCGATGCCACCCTGCGCTGCTCCTTCTCCCCCGAGCCTGGCTTCAGCCT
GGCACAGCTCAACCTCATCTGGCAGCTGACAGACACCAAACAGCTGGTGCACAGTTTCACCGAAGGCC
GGGACCAGGCCAGCGCCTATGCCAACCGCACGGCCCTCTTCCCGGACCTCCTGGCACAAGGCAATGCA
TCCCTGAGGCTGCAGCGCGTGCGTGTGGCGGACGAGGGCAGCTTCACCTGCTTCGTGAGCATCCGGGA
TTTCGGCAGCGCTGCCGTCAGCCTGCAGGTGGCCGCTCCCTACTCGAAGCCCAGCATGACCCTGGAGC
CCAACAAGGACCTGCGGCCAGGGGACACGGTGACCATCACGTGCTCCAGCTACCGGGGCTACCCTGAG
GCTGAGGTGTTCTGGCAGGATGGGCAGGGTGTGCCCCTGACTGGCAACGTGACCACGTCGCAGATGGC
CAACGAGCAGGGCTTGTTTGATGTGCACAGCGTCCTGCGGGTGGTGCTGGGTGCGAATGGCACCTACA
GCTGCCTGGTGCGCAACCCCGTGCTGCAGCAGGATGCGCACGGCTCTGTCACCATCACAGGGCAGCCT
ATGACATTCCCCCCAGAGGCCCTGTGGGTGACCGTGGGGCTGTCTGTCTGTCTCATTGCACTGCTGGT
GGCCCTGGCTTTCGTGTGCTGGAGAAAGATCAAACAGAGCTGTCAGGAGGAGAATGCAGGAGCTGAGG
ACCAGGATGGGGAGGGAGAAGGCTCCAAGACAGCCCTGCAGCCTCTGAAACACTCTGACAGCAAAGAA
GATGATGGACAAGAAATAGCCTGACCATGAGGACCAGGGAGCTGCTACCCCTCCCTACAGCTCCTACC
CTCTGGCTGCAATGGGGCTGCACTGTGAGCCCTGCCCCCAACAGATGCATCCTGCTCTGACAGGTGGG
CTCCTTCTCCAAAGGATGCGATACACAGACCACTGTGCAGCCTTATTTCTCCAATGGACATGATTCCC
AAGTCATCCTGCTGCCTTTTTTCTTATAGACACAATGAACAGACCACCCACAACCTTAGTTCTCTAAG
TCATCCTGCCTGCTGCCTTATTTCACAGTACATACATTTCTTAGGGACACAGTACACTGACCACATCA
CCACCCTCTTCTTCCAGTGCTGCGTGGACCATCTGGCTGCCTTTTTTCTCCAAAAGATGCAATATTCA
GACTGACTGACCCCCTGCCTTATTTCACCAAAGACACGATGCATAGTCACCCCGGCCTTGTTTCTCCA
ATGGCCGTGATACACTAGTGATCATGTTCAGCCCTGCTTCCACCTGCATACAATCTTTTCTTCTCAGA
CAGGGACAGTGCAGCCTCAACATCTCCTGGAGTCTAGAAGCTGTTTCCTTTCCCCTCCTTCCTCCTCT
TGCTCTAGCCTTAATACTGGCCTTTTCCCTCCCTGCCCCAAGTGAAGACAGGGCACTCTGCGCCCACC
ACATGCACAGCTGTGCATGGAGACCTGCAGGTGCACGTGCTGGAACACGTGTGGTTCCCCCCTGGCCC
AGCCTCCTCTGCAGTGCCCCTCTCCCCTGCCCATCCTCCCCACGGAAGCATGTGCTGGTCACACTGGT
TCTCCAGGGGTCTGTGATGGGGCCCCTGGGGGTCAGCTTCTGTCCCTCTGCCTTCTCACCTCTTTGTT
CCTTTCTTTTCATGTATCCATTCAGTTGATGTTTATTGAGCAACTACAGATGTCAGCACTGTGTTAGG
TGCTGGGGGCCCTGCGTGGGAAGATAAAGTTCCTCCCTCAAGGACTCCCCATCCAGCTGGGAGACAGA
CAACTAACTACACTGCACCCTGCG
NOV9b, CG59538-02
Protein Sequence	SEQ ID NO: 134	606 aa	MW at 65211.4kD
MTLEPNKDLRPGDTVTITCSSYQGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLFDVHSILRVVLGA
NGTYSCLVRNPVLQQDAHSSVTITPQRSPTGAVEVQVPEDPVVALVGTDATLRCSFSPEPGFSLAQLN
LIWQLTDTKQLVHSFTEGRDQGSAYANRTALFPDLLAQGNASLRLQRVRVADEGSFTCFVSIRDFGSA
AVSLQVAAPYSKPSMTLEPNKDLRPGDTVTITCSSYQGYPEAEVFWQDGQGVPLTGNVTTSQMANEQG
LFDVHSILRVVLGANGTYSCLVRNPVLQQDAHSSVTITPQRSPTGAVEVQVPEDPVVALVGTDATLRC
SFSPEPGFSLAQLNLIWQLTDTKQLVHSFTEGRDQGSAYANRTALFPDLLAQGNASLRLQRVRVADEG
SFTCFVSIRDFGSAAVSLQVAAPYSKPSMTLEPNKDLRPGDTVTITCSSYRGYPEAEVFWQDGQGVPL
TGNVTTSQMANEQGLFDVHSVLRVVLGANGTYSCLVRNPVLQQDAHGSVTITGQPMTFPPEALWVTVG
LSVCLIALLVALAFVCWRKIKQSCEEENAGAEDQDGEGEGSKTALQPLKHSDSKEDDGQEIA
NOV9c, CG59538-03	SEQ ID NO: 135	1518 bp
DNA Sequence	ORF Start: ATG at 62	ORF Stop: end of sequence
AGCTGTCAGCCGCCTCACAGGAAGATGCTGCGTCGGCGGGGCAGCCCTGGCATGGGTGTGCATGTGGG
TGCAGCCCTGGGAGCACTGTGGTTCTGCCTCACAGGAGCCCTGGAGGTCCAGGTCCCCTGAGGACCCG
GTGGTGGCCCTAGTGGGCACCGATGCCACCCTGCGCTGCTCCTTCTCCCCCGAGCCTGGCTTCAGCCT
GGCACAGCTCAACCTCATCTGGCAGCTGACAGACACCAAACAGCTGGTGCACAGTTTCACCGAAGGCC
GGGACCAGGGCAGCGCCTATGCCAACCGCACGGCCCTCTTCCCGGACCTGCTGGCACAAGCCAATGCA
TCCCTGAGGCTGCAGCGCGTGCGTGTGGCGGACGAGGGCAGCTTCACCTGCTTCGTGAGCATCCGGGA
TTTCGGCAGCGCTGCCGTCAGCCTGCAGGTGGCCGCTCCCTACTCGAAGCCCAGCATGACCCTGGAGC
CCAACAAGGACCTGCGGCCAGGGGACACGGTGACCATCACGTGCTCCAGCTACCAGGGCTACCCTGAG
GCTGACGTGTTCTGGCAGGATGGGCAGGGTGTGCCCCTGACTGGCAACGTGACCACGTCGCAGATGGC
CAACGAGCAGGGCTTGTTTGATGTGCACAGCATCCTGCGGGTGGTGCTGGGTGCAAATGGCACCTACA
GCTGCCTGGTGCGCAACCCCGTGCTGCAGCAGGATGCGCACAGCTCTGTCACCATCACACCCCAGAGA
AGCCCCACAGGAGCCGTGGAGGTCCAGGTCCCTGAGGACCCGGTGGTGGCACTGGTGGGCACCGATGC
CACCCTGCGCTGCTCCTTCTCCCCCGAGCCTGGCTTCAGCCTGGCACAGCTCAACCTCATCTGGCAGC
TGACAGACACCAAACAGCTGGTGCACAGTTTCACCGAAGGCCGGGACCAGGGCAGCGCCTATGCCAAC
CGCACGGCCCTCTTCCCGGACCTGCTGGCACAAGGCAATGCATCCCTGAGGCTGCAGCGCGTGCGTGT
GGCGGACGAGGGCAGCTTCACCTGCTTCGTGAGCATCCGGGATTTCGGCAGCGCTGCCGTCAGCCTGC
AGGTGGCCGCTCCCTACTCGAAGCCCAGCATGACCCTGGAGCCCAACAAGGACCTGCGGCCAGGGGAC
ACGGTGACCATCACGTGCTCCAGCTACCGGGGCTACCCTGAGGCTGAGCGTCCTGCGGGTGGTGCTGG
GTGCGAATGGCACCTACAGCTGCCTGGTGCGCAACCCCGTGCTGCAGCAGGATGCGCACGGCTCTGTC
ACCATCACGGGGCAGCCTATGACATTCCCCCCAGAGGCCCTGTGGGTGACCGTGGGGCTGTCTGTCTG
TCTCATTGCACTGCTGGTGGCCCTGGCTTTCGTGTGCTGGAGAAAGATCAAACAGAGCTGTGAGGAGG
AGAATGCAGGAGCTGAGGACCAGGATGGGGAGGGAGAAGGCTCCAAGACAGCCCTGCAGCCTCTGAAA
CACTCTGACAGCAAAGAAGATG
NOV9c, CG59538-03
Protein Sequence	SEQ ID NO: 136	453 aa	MW at 48763.1kD
MWVQPWEHCGSASQEPWRSRSPEDPVVALVGTDATLRCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFT
EGRDQGSAYANRTALFPDLLAQGNASLRLQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPYSKPSMT
LEPNKDLRPGDTVTITCSSYQGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLFDVHSILRVVLGANG
TYSCLVRNPVLQQDAHSSVTITPQRSPTGAVEVQVPEDPVVALVGTDATLRCSFSPEPGFSLAQLNLI
WQLTDTKQLVHSFTEGRDQGSAYANRTALFPDLLAQGNASLRLQRVRVADEGSFTCFVSIRDFGSAAV
SLQVAAPYSKPSMTLEPNKDLRPGDTVTITCSSYRGYPEAERPAGGAGCEWHLQLPGAQPRAAAGCAR
LCHHHGAAYDIPPRGPVGDRGAVCLSHCTAGGPGFRVLEKDQTEL
NOV9d, CG59538-04	SEQ ID NO: 137	975 bp
DNA Sequence	ORF Start: ATG at 21	ORF Stop: end of sequence
GTCAGCCGCCTCACAGGAAGATGCTGCGTCGGCGGGGCAGCCCTGGCATGGGTGTGCATGTGGGTGCA
GCCCTGGGAGCACTGTGGTTCTGCCTCACAGGAGCCCTCGAGGTCCAGGTCCCTGAAGACCCAGTGGT
GGCACTGGTGGGCACCGATGCCACCCTGTGCTGCTCCTTCTCCCCTGAGCCTGGCTTCAGCCTGGCAC
AGCTCAACCTCATCTGGCAGCTGACAGATACCAAACAGCTGGTGCACAGCTTTGCTGAGGGCCAGGAC
CAGGGCAGCGCCTATGCCAACCGCACGGCCCTCTTCCCGGACCTGCTGGCACAGGGCAACGCATCCCT
GAGGCTGCAGCGCGTGCGTGTGGCGGACGAGGGCAGCTTCACCTGCTTCGTGAGCATCCGGGATTTCG
GCAGCGCTGCCGTCAGCCTGCAGGTGGCCGCTCCCTACTCGAAGCCCAGCATGACCCTGGAGCCCAAC
AAGGACCTGCGGCCAGGGGACACGGTGACCATCACGTGCTCCAGCTACCGGGGCTACCCTGAGGCTGA
GGTGTTCTGGCAGGATGGGCAGGGTGTGCCCCTGACTGGCAACGTGACCACGTCGCAGATGGCCAACG
AGCAGGGCTTGTTTGATGTGCACAGCGTCCTGCGGGTGGTGCTGGGTGCGAATGGCACCTACAGCTGC
CTGGTGCGCAACCCCGTGCTGCAGCAGGATGCGCACGGCTCTGTCACCATCACAGGGCAGCCTATGAC
ATTCCCCCCAGAGGCCCTGTGGGTGACCGTGGGGCTGTCTGTCTGTCTCATTGCACTGCTGGTGGCCC
TGGCTTTCGTGTGCTGGAGAAAGATCAAACAGAGCTGTGAGGAGGAGAATGCAGGAGCTGAGGACCAG
GATGGGGAGGGAGAAGGCTCCAAGACAGCCCTGCAGCCTCTGAAACACTCTGACAGCAAAGAAGATGA
TGGACAAGAAATAGCCTGACCAT
NOV9d, CG59538-04
Protein Sequence	SEQ ID NO: 138	316 aa	MW at 33790.8kD
MLRRRGSPGMGVHVGAALGALWFCLTGALEVQVPEDPVVALVGTDATLCCSFSPEPGFSLAQLNLIWQ
LTDTKQLVHSFAEGQDQGSAYANRTALFPDLLAQGNASLRLQRVRVADEGSFTCFVSIRDFGSAAVSL
QVAAPYSKPSMTLEPNKDLRPGDTVTITCSSYRGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLFDV
HSVLRVVLGANGTYSCLVRNPVLQQDAHGSVTITGQPMTFPPEALWVTVGLSVCLIALLVALAFVCWR
KIKQSCEEENAGAEDQDGEGEGSKTALQPLKHSDSKEDDGQEIA
NOV9e, CG59538-05	SEQ ID NO: 139	1683 bp
DNA Sequence	ORF Start: ATG at 25	ORF Stop: end of sequence
AGCTGTCAGCCGCCTCACAGGAAGATGCTGCGTCGGCGGGGCAGCCCTGGCATGGGTGTGCATGTGGG
TGCAGCCCTGGGAGCACTGTGGTTCTGCCTCACAGGAGCCCTGGAGGTCCAGGTCCCTGAAGACCCAG
TGGTGGCACTGGTGGGCACCGATGCCACCCTGTGCTGCTCCTTCTCCCCTGAGCCTGGCTTCAGCCTG
GCACAGCTCAACCTCATCTGGCAGCTGACAGATACCAAACAGCTGGTGCACAGCTTTGCTGAGGGCCA
GGACCAGGGCAGCGCCTATGCCAACCGCACGGCCCTCTTCCCGGACCTGCTGCCACAGGGCAACCCAT
CCCTGAGCCTGCAGCGCGTGCGTGTGGCGGACGAGGGCAGCTTCACCTGCTTCGTGAGCATCCGGGAT
TTCGGCACCGCTGCCGTCAGCCTGCAGGTGGCCGCTCCCTACTCGAAGCCCAGCATGACCCTGGAGCC
CAACAAGGACCTGCGGCCAGGGGACACGGTGACCATCACGTGCTCCAGCTACCAGGGCTACCCTGAGG
CTGAGGTCTTCTGGCAGGATGGGCAGGGTGTGCCCCTGACTGGCAACCTGACCACGTCGCAGATGGCC
AACGAGCAGGGCTTGTTTGATGTGCACAGCATCCTGCGGGTGGTGCTGGGTGCAAATGGCACCTACAG
CTGCCTGGTGCGCAACCCCGTGCTGCAGCAGGATGCGCACAGCTCTGTCACCATCACACCCCAGAGAA
GCCCCACAGGAGCCGTGGAGGTCCAGGTCCCTGAGGACCCGGTGGTGGCCCTAGTGGGCACCGATGCC
ACCCTGCGCTGCTCCTTCTCCCCCGAGCCTGGCTTCAGCCTGGCACAGCTCAACCTCATCTGGCAGCT
GACAGACACCAAACAGCTGGTGCACAGTTTCACCGAAGGCCGGGACCAGGGCAGCGCCTATGCCAACC
GCACGGCCCTCTTCCCGGACCTGCTGGCACAAGGCAATGCATCCCTGAGGCTGCAGCGCGTGCGTGTG
GCGGACGAGGGCAGCTTCACCTGCTTCGTGAGCATCCGGGATTTCGGCAGCGCTGCCGTCAGCCTGCA
GCTGGCCGCTCCCTACTCGAAGCCCAGCATGACCCTGGAGCCCAACAAGGACCTGCGGCCAGGGGACA
CGGTGACCATCACGTGCTCCAGCTACCGGGGCTACCCTGAGGCTGAGGTGTTCTGGCAGGATGGGCAG
GGTGTGCCCCTGACTGGCAACGTGACCACGTCGCAGATGGCCAACGAGCAGGGCTTGTTTGATGTGCA
CAGCGTCCTGCGGGTGCTGCTGGGTGCGAATGGCACCTACAGCTGCCTGGTGCGCAACCCCGTGCTGC
AGCAGGATGCGCACGGCTCTGTCACCATCACAGGGCAGCCTATGACATTCCCCCCAGAGGCCCTGTGG
GTGACCGTGGGGCTGTCTGTCTGTCTCATTGCACTGCTGGTGGCCCTGGCTTTCGTGTGCTGGAGAAA
GATCAAACAGAGCTGTGAGGAGGAGAATGCAGGAGCTGAGGACCAGGATGGGGAGGGAGAAGGCTCCA
AGACAGCCCTGCAGCCTCTGAAACACTCTGACAGCAAAGAAGATGATGGACAAGAAATAGCCTGACCA
TGAGGACCAGGGAGCTGCTACCCCTCCCTACAGCTCCTACCCTCTGGCTGC
NOV9e, CG59538-05
Protein Sequence	SEQ ID NO: 140	534 aa	MW at 57234.9kD
MLRRRGSPGMGVHVGAALGALWFCLTGALEVQVPEDPVVALVGTDATLCCSFSPEPGFSLAQLNLIWQ
LTDTKQLVHSFAEGQDQCSAYANRTALFPDLLAQGNASLRLQRVRVADEGSFTCFVSIRDFGSAAVSL
QVAAPYSKPSMTLEPNKDLRPGDTVTITCSSYQGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLFDV
HSILRVVLGANGTYSCLVRNPVLQQDAHSSVTITPQRSPTGAVEVQVPEDPVVALVGTDATLRCSFSP
EPGFSLAQLNLIWQLTDTKQLVHSFTEGRDQGSAYANRTALFPDLLAQGNASLRLQRVRVADEGSFTC
FVSIRDFGSAAVSLQVAAPYSKPSMTLEPNKDLRPGDTVTITCSSYRGYPEAEVFWQDGQGVPLTGNV
TTSQMANEQGLFDVHSVLRVVLGANGTYSCLVRNPVLQQDAHGSVTITGQPMTFPPEALWVTVGLSVC
LIALLVALAFVCWRKIKQSCEEENAGAEDQDGEGEGSKTALQPLKHSDSKEDDGQEIA
NOV9f, CG59538-06	SEQ ID NO: 141	670 bp
DNA Sequence	ORF Start: at 11	ORF Stop: end of sequence
CACCGGATCCGCCCTGGAGGTCCAGGTCCCTGAAGACCCAGTGGTGGCACTGGTGGGCACCGATGCCA
CCCTGTGCTGCTCCTTCTCCCCTGAGCCTGGCTTCAGCCTGGCACAGCTCAACCTCATCTGGCAGCTG
ACAGATACCAAACAGCTGGTGCACAGCTTTGCTGAGGGCCAGGACCAGGGCAGCGCCTATGCCAACCG
CACGGCCCTCTTCCCGGACCTGCTGGCACAGGGCAACGCATCCCTCAGGCTGCAGCGCGTGCGTGTGG
CGGACGAGGGCAGCTTCACCTGCTTCGTGAGCATCCGGGATTTCGGCAGCGCTGCCGTCAGCCTCCAG
GTGGCCGCTCCCTACTCGAAGCCCAGCATGACCCTGGAGCCCAACAAGGACCTGCGGCCAGGGGACAC
GGTGACCATCACGTGCTCCAGCTACCGGGGCTACCCTGAGGCTGAGGTGTTCTGGCAGGATGGGCAGG
GTGTGCCCCTGACTGGCAACGTGACCACGTCGCAGATGGCCAACGAGCAGGGCTTGTTTGATGTGCAC
AGCGTCCTGCGGGTGGTGCTGGGTGCAAATGGCACCTACAGCTGCCTGGTGCGCAACCCCGTGCTGCA
GCAGGATGCGCACGGCTCTGTCACCATCACAGGGCAGCCTATGACATTCCTCGAGCGC
NOV9f, CG59538-06
Protein Sequence	SEQ ID NO: 142	217 aa	MW at 23286.9kD
ALEVQVPEDPVVALVGTDATLCCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFAEGQDQGSAYANRTAL
FPDLLAQGNASLRLQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPYSKPSMTLEPNKDLRPGDTVTI
TCSSYRGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLFDVHSVLRVVLGANGTYSCLVRNPVLQQDA
HGSVTITGQPMTF
NOV9g, CG59538-07	SEQ ID NO: 143	1324 bp
DNA Sequence	ORF Start: at 11	ORF Stop: end of sequence
CACCGGATCCGCCCTGGAGGTCCAGGTCCCTGAAGACCCAGTGGTGGCACTGGTGGGCACCGATGCCA
CCCTGTGCTGCTCCTTCTCCCCTGAGCCTGGCTTCAGCCTGGCACAGCTCAACCTCATCTGGCAGCTG
ACAGATACCAAACAGCTGGTGCACAGCTTTGCTGAGGGCCAGGACCAGGGCAGCGCCTATGCCAACCG
CACGGCCCTCTTCCCGGACCTGCTGGCACAGGGCAACGCATCCCTGAGGCTGCAGCGCGTGCGTGTGG
CGGACGAGGGCAGCTTCACCTGCTTCGTGAGCATCCGGGATTTCGGCAGCGCTGCCGTCAGCCTGCAG
GTGGCCGCTCCCTACTCGAAGCCCAGCATGACCCTGGAGCCCAACAAGGACCTGCGGCCAGGGGACAC
GGTGACCATCACGTGCTCCAGCTACCAGGGCTACCCTGAGGCTGAGGTGTTCTGGCAGGATGGGCAGG
GTGTGCCCCTGACTGGCAACGTGACCACGTCGCAGATGGCCAACGAGCAGGGCTTGTTTGATGTGCAC
AGCATCCTGCGGGTGGTGCTGGGTGCGAATGGCACCTACAGCTGCCTGGTGCGCAACCCCGTGCTGCA
GCAGCATGCGCACGGCTCTGTCACCATCACACCCCAGAGAAGCCCCACAGGAGCCGTGGAGGTCCAGG
TCCCTGAGGACCCGGTGGTGGCCCTAGTGGGCACCGATGCCACCCTGCGCTGCTCCTTCTCCCCCGAG
CCTGGCTTCAGCCTGGCACAGCTCAACCTCATCTGCCAGCTGACAGACACCAAACAGCTGGTGCACAG
TTTCACCGAAGGCCGGGACCAGGGCAGCGCCTATGCCAACCGCACGGCCCTCTTCCCGGACCTGCTGG
CACAAGGCAATGCATCCCTGAGGCTGCAGCGCGTGCGTGTGGCGGACGAGGGCAGCTTCACCTGCTTC
GTGAGCATCCGGGATTTCGGCAGCGCTGCCGTCAGCCTGCAGGTGGCCGCTCCCTACTCGAAGCCCAG
CATGACCCTGGAGCCCAACAAGGACCTGCGGCCAGGGGACACGGTGACCATCACGTGCTCCAGCTACC
GGGGCTACCCTGAGGCTGAGGTGTTCTGGCAGGATGGGCAGGGTGTGCCCCTGACTGGCAACGTGACC
ACGTCGCAGATGGCCAACGAGCAGGGCTTGTTTGATGTGCACAGCGTCCTGCGGGTGGTGCTGGGTGC
GAATGGCACCTACAGCTGCCTGGTGCGCAACCCCGTGCTGCAGCAGGATGCGCACGGCTCTGTCACCA
TCACAGGGCAGCCTATGACATTCCTCGAGCCG
NOV9g, CG59538-07
Protein Sequence	SEQ ID NO: 144	435 aa	MW at 46700.9kD
ALEVQVPEDPVVALVGTDATLCCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFAEGQDQGSAYANRTAL
FPDLLAQGNASLRLQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPYSKPSMTLEPNKDLRPGDTVTI
TCSSYQGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLFDVHSILRVVLGANGTYSCLVRNPVLQQDA
HGSVTITPQRSPTGAVEVQVPEDPVVALVGTDATLRCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFTE
GRDQGSAYANRTALFPDLLAQGNASLRLQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPYSKPSMTL
EPNKDLRPGDTVTITCSSYRGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLFDVHSVLRVVLGANGT
YSCLVRNPVLQQDAHGSVTITGQPMTF
NOV9h, 13382231	SEQ ID NO: 145	2650 bp
DNA Sequence	ORF Start: ATG at 62	ORF Stop: end of sequence
AGCTGTCAGCCGCCTCACAGGAAGATGCTGCGTCGGCGCGGCAGCCCTGGCATGGGTGTGCATGTGGG
TGCAGCCCTGGGAGCACTGTGGTTCTGCCTCACAGGAGCCCTGGAGGTCCAGGTCCCCTGAGGACCCG
GTGGTGGCCCTAGTGGGCACCGATGCCACCCTGCGCTGCTCCTTCTCCCCCGAGCCTGGCTTCAGCCT
GACACAGCTCAACCTCATCTGGCAGCTGACAGACACCAAACAGCTGGTGCACAGTTTCACCGAAGGCC
GGGACCAGGGCAGCGCCTATGCCAACCGCACGGCCCTCTTCCCGGACCTGCTGGCACAAGGCAATGCA
TCCCTGAGGCTGCAGCGCGTGCGTGTGGCGGACGAGGGCAGCTTCACCTGCTTCGTGAGCATCCGGGA
TTTCGGCAGCGCTGCCGTCAGCCTGCAGGTGGCCGCTCCCTACTCGAAGCCCAGCATGACCCTGGAGC
CCAACAAGGACCTGCGGCCAGGGGACACGGTGACCATCACGTGCTCCAGCTACCAGGGCTACCCTGAG
GCTGAGGTGTTCTGGCAGGATGGGCAGGGTGTGCCCCTGACTGGCAACGTGACCACGTCGCAGATGGC
CAACGAGCAGGGCTTGTTTGATGTGCACAGCATCCTGCGGGTGGTGCTGGGTGCAAATGGCACCTACA
GCTGCCTGGTGCGCAACCCCGTGCTGCAGCAGGATGCGCACAGCTCTGTCACCATCACACCCCAGAGA
AGCCCCACAGGAGCCGTGGAGGTCCAGGTCCCTGAGGACCCGGTGGTGGCCCTAGTGGGCACCGATGC
CACCCTGCGCTGCTCCTTCTCCCCCGAGCCTGGCTTCACCCTGGCACAGCTCAACCTCATCTGGCAGC
TGACAGACACCAAACAGCTGGTGCACAGTTTCACCGAAGGCCGGGACCAGGGCAGCGCCTATCCCAAC
CGCACGGCCCTCTTCCCGGACCTGCTGGCACAAGGCAATGCATCCCTGAGGCTGCAGCGCGTGCGTGT
GGCGGACGAGGGCAGCTTCACCTGCTTCGTGAGCATCCGGGATTTCGGCAGCGCTGCCGTCAGCCTGC
AGGTGGCCGCTCCCTACTCGAAGCCCAGCATGACCCTGGACCCCAACAAGGACCTGCGGCCAGGGCAC
ACGGTGACCATCACGTGCTCCACCTACCGGGGCTACCCTGAGGCTGAGGTGTTCTGGCAGGATGGGCA
GGGTGTCCCCCTGACTGGCAACGTGACCACGTCGCAGATGGCCAACGAGCAGGCCTTGTTTGATGTGC
ACAGCGTCCTGCGGGTGGTGCTGGGTGCGAATGCCACCTACAGCTGCCTGGTGCGCAACCCCGTGCTG
CAGCAGGATGCGCACGGCTCTGTCACCATCACAGGGCAGCCTATGACATTCCCCCCAGAGGCCCTGTG
GGTGACCGTGGGGCTGTCTGTCTGTCTCATTGCACTGCTGGTGGCCCTGGCTTTCGTGTGCTGGAGAA
AGATCAAACAGAGCTGTGAGGAGGAGAATGCAGGAGCTGAGGACCAGGATGGGCAGGGAGAAGGCTCC
AAGACAGCCCTGCAGCCTCTGAAACACTCTGACAGCAAAGAAGATGATGGACAAGAAATAGCCTGACC
ATGAGGACCAGGGAGCTGCTACCCCTCCCTACAGCTCCTACCCTCTGGCTGCAATGGGGCTGCACTGT
GAGCCCTGCCCCCAACAGATGCATCCTGCTCTGACAGGTGGGCTCCTTCTCCAAAGGATGCGATACAC
AGACCACTGTGCAGCCTTATTTCTCCAATGGACATGATTCCCAAGTCATCCTGCTGCCTTTTTTCTTA
TAGACACAATGAACAGACCACCCACAACCTTAGTTCTCTAAGTCATCCTGCCTGCTGCCTTATTTCAC
AGTACATACATTTCTTAGGGACACAGTACACTGACCACATCACCACCCTCTTCTTCCAGTGCTGCGTG
GACCATCTGGCTGCCTTTTTTCTCCAAAAGATGCAATATTCAGACTGACTGACCCCCTGCCTTATTTC
ACCAAAGACACGATGCATAGTCACCCCGGCCTTGTTTCTCCAATGGCCGTGATACACTAGTGATCATG
TTCAGCCCTGCTTCCACCTGCATAGAATCTTTTCTTCTCAGACAGGGACAGTGCGGCCTCAACATCTC
CTGGGGTCTAGAAGCTGTTTCCTTTCCCCTCCTTCCTCCTCTTGCTCTAGCCTTAATACTGGCCTTTT
CCCTCCCTGCCCCAAGTGAAGACAGGGCACTCTGCGCCCACCACATGCACAGCTGTGCATGGAGACCT
GCAGGTGCACGTGCTGGAACACGTGTGGTTCCCCCCTGGCCCAGCCTCCTCTGCAGTGCCCCTCTCCC
CTGCCCATCCTCCCCACGGAAGCATGTGCTGGTCACACTGGTTCTCCAGGGGTCTGTGATGGGGCCCC
TGGGGGTCAGCTTCTGTCCCTCTGCCTTCTCACCTCTTTGTTCCTTTCTTTTCATGTATCCATTCAGT
TGATGTTTATTGAGCAACTACAGATGTCAGCACTGTGTTAGGTGCTGGGGGCCCTGCGTGGGAAGATA
AAGTTCCTCCCTCAAGGACTCCCCATCCAGCTGGGAGACAGACAACTAACTACACTGCACCCTGCG
NOV9h, 13382231
Protein Sequence	SEQ ID NO: 146	522 aa	MW at 56436.7kD
MWVQPWEHCGSASQEPWRSRSPEDPVVALVGTDATLRCSFSPEPGFSLTQLNLIWQLTDTKQLVHSFT
EGRDQGSAYANRTALFPDLLAQGNASLRLQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPYSKPSMT
LEPNKDLRPGDTVTITCSSYQGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLFDVHSILRVVLGANG
TYSCLVRNPVLQQDAHSSVTITPQRSPTGAVEVQVPEDPVVALVGTDATLRCSFSPEPGFSLAQLNLI
WQLTDTKQLVHSFTEGRDQGSAYANRTALFPDLLAQGNASLRLQRVRVADEGSFTCFVSIRDFGSAAV
SLQVAAPYSKPSMTLEPNKDLRPGDTVTITCSSYRGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLF
DVHSVLRVVLGANGTYSCLVRNPVLQQDAHGSVTITGQPMTFPPEALWVTVGLSVCLIALLVALAFVC
WRKIKQSCEEENAGAEDQDGEGEGSKTALQPLKHSDSKEDDGQEIA
NOV9i, 13376726	SEQ ID NO: 147	2650 bp
DNA Sequence	ORF Start: ATG at 62	ORF Stop: end of sequence
AGCTGTCAGCCGCCTCACAGGAAGATGCTGCGTCGCCGGGGCAGCCCTGGCATGGGTGTGCATGTGGG
TGCAGCCCTGGGAGCACTGTGGTTCTGCCTCACAGGAGCCCTGGAGGTCCAGGTCCCCTGAGGACCCG
GTGGTGGCCCTAGTGGGCACCGATGCCACCCTGCGCTGCTCCTTCTCCCCCGAGCCTGGCTTCAGCCT
GGCACAGCTCAACCTCATCTGGCAGCTGACAGACACCAAACAGCTGGTGCACAGTTTCACCGAAGGCC
GGGACCAGGGCAGCGCCTATGCCAACCGCACGGCCCTCTTCCCGGACCTGCTGGCACAAGGCAATGCA
TCCCTCAGGCTGCAGCGCGTGCGTGTGGCGGACGAGGGCAGCTTCACCTGCTTCGTGAGCATCCGGGA
TTTCGGCAGCGCTGCCGTCAGCCTGCAGGTGGCCGCTCCCTACTCGAAGCCCAGCATGACCCTGGAGC
CCAACAAGGACCTGCGGCCAGGGGACACGGTGACCATCACGTGCTCCAGCTACCGGGGCTACCCTGAG
GCTGAGGTGTTCTGGCAGGATGGGCAGGGTGTGCCCCTGACTGGCAACGTGACCACGTCGCAGATGGC
CAACGAGCAGGGCTTGTTTGATGTGCACAGCATCCTGCGGGTGGTGCTGGGTGCAAATGGCACCTACA
GCTGCCTGGTGCGCAACCCCGTGCTGCAGCAGGATGCGCACAGCTCTGTCACCATCACACCCCAGAGA
AGCCCCACAGGAGCCGTGGAGGTCCAGGTCCCTGAGGACCCGGTGGTGGCCCTAGTCGGCACCGATGC
CACCCTGCGCTGCTCCTTCTCCCCCGAGCCTGGCTTCAGCCTGGCACAGCTCAACCTCATCTGGCAGC
TGACAGACACCAAACAGCTGGTGCACAGTTTCACCGAAGGCCGGGACCAGGGCAGCGCCTATGCCAAC
CGCACGGCCCTCTTCCCGGACCTGCTGGCACAAGGCAATGCATCCCTGAGGCTGCAGCGCGTGCGTGT
GGCGGACGAGGGCAGCTTCACCTGCTTCGTGAGCATCCGGGATTTCGGCAGCGCTGCCGTCAGCCTGC
AGGTGGCCGCTCCCTACTCGAAGCCCAGCATGACCCTGGAGCCCAACAAGGACCTGCGGCCAGGGGAC
ACGGTGACCATCACGTGCTCCAGCTACCGGGGCTACCCTGAGGCTGAGGTGTTCTGGCAGGATGGGCA
GGGTGTGCCCCTGACTGGCAACGTGACCACGTCGCAGATGGCCAACGAGCAGGGCTTGTTTGATGTGC
ACAGCGTCCTGCGGGTGGTGCTGGGTGCGAATGGCACCTACAGCTGCCTGGTGCGCAACCCCGTGCTG
CAGCAGGATGCGCACGGCTCTGTCACCATCACAGGGCAGCCTATGACATTCCCCCCAGAGGCCCTGTG
GGTGACCGTGGGGCTGTCTGTCTGTCTCATTGCACTGCTGGTCGCCCTGGCTTTCGTGTGCTGGAGAA
AGATCAAACAGAGCTGTGAGGAGGAGAATGCAGGAGCTGAGGACCAGGATGGGGAGGGAGAAGGCTCC
AAGACAGCCCTGCAGCCTCTGAAACACTCTGACAGCAAAGAAGATGATGGACAAGAAATAGCCTGACC
ATGAGGACCAGGGAGCTGCTACCCCTCCCTACAGCTCCTACCCTCTGGCTGCAATGGGGCTGCACTGT
GAGCCCTGCCCCCAACAGATGCATCCTGCTCTGACAGGTGGGCTCCTTCTCCAAAGGATGCGATACAC
AGACCACTGTGCAGCCTTATTTCTCCAATGGACATGATTCCCAAGTCATCCTGCTGCCTTTTTTCTTA
TAGACACAATGAACAGACCACCCACAACCTTAGTTCTCTAAGTCATCCTGCCTGCTGCCTTATTTCAC
AGTACATACATTTCTTAGGGACACAGTACACTGACCACATCACCACCCTCTTCTTCCAGTGCTGCGTG
GACCATCTGGCTGCCTTTTTTCTCCAAAAGATGCAATATTCAGACTGACTGACCCCCTGCCTTATTTC
ACCAAAGACACGATGCATAGTCACCCCGGCCTTGTTTCTCCAATGGCCGTGATACACTAGTGATCATG
TTCAGCCCTGCTTCCACCTGCATAGAATCTTTTCTTCTCAGACAGGGACAGTGCGGCCTCAACATCTC
CTGGGGTCTAGAAGCTGTTTCCTTTCCCCTCCTTCCTCCTCTTGCTCTAGCCTTAATACTGGCCTTTT
CCCTCCCTGCCCCAAGTGAAGACAGGGCACTCTGCGCCCACCACATGCACAGCTGTGCATGGAGACCT
GCAGGTGCACGTGCTGGAACACGTGTGGTTCCCCCCTGGCCCAGCCTCCTCTGCAGTGCCCCTCTCCC
CTGCCCATCCTCCCCACGGAAGCATGTGCTGGTCACACTGGTTCTCCAGGGGTCTGTGATGGGGCCCC
TGGGGGTCAGCTTCTGTCCCTCTGCCTTCTCACCTCTTTGTTCCTTTCTTTTCATGTATCCATTCAGT
TGATGTTTATTGAGCAACTACAGATGTCAGCACTGTGTTAGGTGCTGGGGGCCCTGCGTGGGAAGATA
AAGTTCCTCCCTCAAGGACTCCCCATCCAGCTGGGAGACAGACAACTAACTACACTGCACCCTGCG
NOV9i, 13376726
Protein Sequence	SEQ ID NO: 148	522 aa	MW at 56436.7kD
MWVQPWEHCGSASQEPWRSRSPEDPVVALVGTDATLRCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFT
EGRDQGSAYANRTALFPDLLAQGNASLRLQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPYSKPSMT
LEPNKDLRPGDTVTITCSSYRGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLFDVHSILRVVLGANG
TYSCLVRNPVLQQDAHSSVTITPQRSPTGAVEVQVPEDPVVALVGTDATLRCSFSPEPGFSLAQLNLI
WQLTDTKQLVHSFTEGRDQGSAYANRTALFPDLLAQGNASLRLQRVRVADEGSFTCFVSIRDFGSAAV
SLQVAAPYSKPSMTLEPNKDLRPGDTVTITCSSYRGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLF
DVHSVLRVVLGANGTYSCLVRNPVLQQDAHGSVTITGQPMTFPPEALWVTVGLSVCLIALLVALAFVC
WRKIKQSCEEENAGAEDQDGEGEGSKTALQPLKHSDSKEDDGQEIA
NOV9j, 13382229	SEQ ID NO: 149	2650 bp
DNA Sequence	ORF Start: ATG at 62	ORF Stop: end of sequence
AGCTGTCAGCCGCCTCACAGGAAGATGCTGCGTCGGCGGGGCAGCCCTGGCATGGGTGTGCATGTGGG
TGCAGCCCTGGGAGCACTGTGGTTCTGCCTCACAGGAGCCCTGGAGGTCCAGGTCCCCTGAGGACCCG
GTGGTGGCCCTAGTGGGCACCGATGCCACCCTGCGCTGCTCCTTCTCCCCCGAGCCTGGCTTCAGCCT
GGCACAGCTCAACCTCATCTGGCAGCTGACAGACACCAAACAGCTGGTGCACAGTTTCACCGAAGGCC
GGGACCAGGGCAGCGCCTATGCCAACCGCACGGCCCTCTTCCCGGACCTGCTGGCACAAGGCAATGCA
TCCCTGAGGCTGCAGCGCGTGCGTGTGGCGGACGAGGGCAGCTTCACCTGCTTCGTGAGCATCCGGGA
TTTCGGCAGCGCTGCCGTCAGCCTGCAGGTGGCCGCTCCCTACTCGAAGCCCAGCATGACCCTGGAGC
CCAACAAGGACCTGCGGCCAGGGGACACGGTGACCATCACGTGCTCCAGCTACCAGGGCTACCCTGAG
GCTGAGGTGTTCTGGCAGGATGGGCAGGGTGTGCCCCTGACTGGCAACGTGACCACGTCGCAGATGGC
CAACGAGCAGGGCTTGTTTGATGTGCACAGCGTCCTGCGGGTGGTGCTGGGTGCAAATGGCACCTACA
GCTGCCTGGTGCGCAACCCCGTGCTGCAGCAGGATGCGCACAGCTCTGTCACCATCACACCCCAGAGA
AGCCCCACAGGAGCCGTGGAGGTCCAGGTCCCTGAGGACCCGGTGGTGGCCCTAGTGGGCACCGATGC
CACCCTGCGCTGCTCCTTCTCCCCCGAGCCTGGCTTCAGCCTGGCACAGCTCAACCTCATCTGGCAGC
TGACAGACACCAAACAGCTGGTGCACAGTTTCACCGAAGGCCGGGACCAGGGCAGCGCCTATGCCAAC
CGCACGGCCCTCTTCCCGGACCTGCTGGCACAAGGCAATGCATCCCTGAGGCTGCAGCGCGTGCGTGT
GGCGGACGAGCGCAGCTTCACCTGCTTCGTGAGCATCCGGGATTTCGGCAGCGCTGCCGTCAGCCTGC
AGGTGGCCGCTCCCTACTCGAAGCCCAGCATGACCCTGGAGCCCAACAAGGACCTGCGGCCAGGGGAC
ACGGTGACCATCACGTGCTCCAGCTACCGGGGCTACCCTGAGGCTGAGGTGTTCTGGCAGGATGGGCA
GGGTGTGCCCCTGACTGGCAACGTGACCACGTCGCAGATGGCCAACGAGCAGGGCTTGTTTGATGTGC
ACAGCGTCCTGCGGGTGGTGCTGGGTGCGAATGGCACCTACAGCTGCCTGGTGCGCAACCCCGTGCTG
CAGCAGGATGCGCACGGCTCTGTCACCATCACACGGCAGCCTATGACATTCCCCCCAGAGGCCCTGTG
GGTGACCGTGGGGCTGTCTGTCTGTCTCATTGCACTGCTGGTGGCCCTGGCTTTCGTGTGCTGGAGAA
AGATCAAACAGAGCTGTGAGGAGGAGAATCCAGGAGCTGAGGACCAGGATGGGGAGGGAGAAGGCTCC
AAGACAGCCCTGCAGCCTCTGAAACACTCTGACAGCAAAGAAGATGATGGACAAGAAATAGCCTGACC
ATGAGGACCAGGGAGCTGCTACCCCTCCCTACAGCTCCTACCCTCTGGCTGCAATGGGGCTGCACTGT
GAGCCCTGCCCCCAACAGATGCATCCTGCTCTGACAGGTGGGCTCCTTCTCCAAAGGATGCGATACAC
AGACCACTGTGCAGCCTTATTTCTCCAATGGACATGATTCCCAAGTCATCCTGCTGCCTTTTTTCTTA
TAGACACAATGAACAGACCACCCACAACCTTAGTTCTCTAAGTCATCCTGCCTGCTGCCTTATTTCAC
AGTACATACATTTCTTAGGGACACAGTACACTGACCACATCACCACCCTCTTCTTCCAGTGCTGCGTG
GACCATCTGGCTGCCTTTTTTCTCCAAAAGATGCAATATTCAGACTGACTGACCCCCTGCCTTATTTC
ACCAAAGACACGATGCATAGTCACCCCGGCCTTGTTTCTCCAATGGCCGTGATACACTAGTGATCATG
TTCAGCCCTGCTTCCACCTGCATAGAATCTTTTCTTCTCAGACAGGGACAGTGCGGCCTCAACATCTC
CTGGGGTCTAGAAGCTGTTTCCTTTCCCCTCCTTCCTCCTCTTGCTCTAGCCTTAATACTGGCCTTTT
CCCTCCCTGCCCCAAGTGAAGACAGGGCACTCTGCGCCCACCACATGCACAGCTGTGCATGGAGACCT
GCAGGTGCACGTGCTGGAACACGTGTGGTTCCCCCCTGGCCCAGCCTCCTCTGCAGTGCCCCTCTCCC
CTGCCCATCCTCCCCACGGAAGCATGTGCTGGTCACACTGGTTCTCCAGGGGTCTGTGATGGGGCCCC
TGGGGGTCAGCTTCTGTCCCTCTGCCTTCTCACCTCTTTGTTCCTTTCTTTTCATGTATCCATTCAGT
TGATGTTTATTGACCAACTACAGATGTCAGCACTGTGTTAGGTGCTGGGGGCCCTGCGTGGGAAGATA
AAGTTCCTCCCTCAAGGACTCCCCATCCAGCTGGGAGACAGACAACTAACTACACTGCACCCTGCG
NOV9j, 13382229
Protein Sequence	SEQ ID NO: 150	522 aa	MW at 56436.7kD
MWVQPWEHCGSASQEPWRSRSPEDPVVALVGTDATLRCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFT
EGRDQGSAYANRTALFPDLLAQGNASLRLQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPYSKPSMT
LEPNKDLRPGDTVTITCSSYQGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLFDVHSVLRVVLGANG
TYSCLVRNPVLQQDAHSSVTITPQRSPTGAVEVQVPEDPVVALVGTDATLRCSFSPEPGFSLAQLNLI
WQLTDTKQLVHSFTEGRDQGSAYANRTALFPDLLAQGNASLRLQRVRVADEGSFTCFVSIRDFGSAAV
SLQVAAPYSKPSMTLEPNKDLRPGDTVTITCSSYRGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLF
DVHSVLRVVLGANGTYSCLVRNPVLQQDAHGSVTITGQPMTFPPEALWVTVGLSVCLIALLVALAFVC
WRKIKQSCEEENAGAEDQDGEGEGSKTALQPLKHSDSKEDDGQEIA
NOV9k, 13376724	SEQ ID NO: 151	2650 bp
DNA Sequence	ORF Start: ATG at 62	ORF Stop: end of sequence
AGCTGTCAGCCGCCTCACAGGAAGATGCTGCGTCGGCGGGGCAGCCCTGGCATGGGTGTGCATGTGGG
TGCAGCCCTGGGAGCACTGTGGTTCTGCCTCACAGGAGCCCTGGAGGTCCAGGTCCCCTGAGGACCCG
GTGGTGGCCCTAGTGGGCACCGATGCCACCCTGCGCTGCTCCTTCTCCCCCGAGCCTGGCTTCAGCCT
GGCACAGCTCAACCTCATCTGGCAGCTGACAGACACCAAACAGCTGGTGCACAGTTTCACCGAAGGCC
GGGACCAGGGCAGCGCCTATGCCAACCGCACGGCCCTCTTCCCGGACCTGCTGGCACAAGGCAATGCA
TCCCTGAGGCTGCAGCGCGTGCGTGTGGCGGACGAGGGCAGCTTCACCTGCTTCGTGAGCATCCGGGA
TTTCGGCAGCGCTGCCGTCAGCCTGCAGGTGGCCGCTCCCTACTCGAAGCCCAGCATGACCCTGGAGC
CCAACAAGGACCTGCGGCCAGGGGACACGGTGACCATCACGTGCTCCAGCTACCAGGGCTACCCTGAG
GCTGAGGTGTTCTGGCAGGATGGGCAGGGTGTGCCCCTGACTGGCAACGTGACCACGTCGCAGATGGC
CAACGAGCAGGGCTTGTTTGATGTGCACAGCATCCTGCGGGTGGTGCTGGGTGCAAATGGCACCTACA
GCTGCCTGGTGCGCAACCCCGTGCTGTAGCAGGATGCGCACAGCTCTGTCACCATCACACCCCAGAGA
AGCCCCACAGGAGCCGTGGAGGTCCAGGTCCCTGAGGACCCGGTGGTGGCCCTAGTGCGCACCGATGC
CACCCTGCGCTGCTCCTTCTCCCCCGAGCCTGGCTTCAGCCTGGCACAGCTCAACCTCATCTGGCAGC
TGACAGACACCAAACAGCTGGTGCACAGTTTCACCGAAGGCCGGGACCAGGGCAGCGCCTATGCCAAC
CGCACGGCCCTCTTCCCGGACCTGCTGGCACAAGGCAATGCATCCCTGAGGCTGCAGCGCGTGCGTGT
GGCGGACGAGGGCAGCTTCACCTGCTTCGTGAGCATCCGGGATTTCGGCAGCGCTGCCGTCAGCCTGC
AGGTGGCCGCTCCCTACTCGAAGCCCAGCATGACCCTGGAGCCCAACAAGGACCTGCGGCCAGGGGAC
ACGGTGACCATCACGTGCTCCAGCTACCGGGGCTACCCTGAGGCTGAGGTGTTCTGGCAGGATGGGCA
GGGTGTGCCCCTGACTGGCAACGTGACCACGTCGCAGATGGCCAACGAGCAUGGCTTGTTTGATGTGC
ACAGCGTCCTGCGGGTGGTGCTGGGTGCGAATGGCACCTACAGCTGCCTCGTGCGCAACCCCGTGCTG
CAGCAGGATGCGCACGGCTCTGTCACCATCACAGGGCAGCCTATGACATTCCCCCCAGAGGCCCTGTG
GGTGACCGTGGGGCTGTCTGTCTGTCTCATTGCACTGCTGGTGGCCCTGGCTTTCGTGTGCTGGAGAA
AGATCAAACAGAGCTGTGAGGAGGAGAATGCAGGAGCTGAGGACCAGGATGGGGAGGGAGAAGCCTCC
AAGACAGCCCTGCAGCCTCTGAAACACTCTGACAGCAAAGAAGATGATGGACAAGAAATAGCCTGACC
ATGAGGACCAGGGAGCTGCTACCCCTCCCTACAGCTCCTACCCTCTGGCTGCAATGGGGCTGCACTGT
GAGCCCTGCCCCCAACAGATGCATCCTGCTCTGACAGGTGGGCTCCTTCTCCAAAGGATGCGATACAC
AGACCACTGTGCAGCCTTATTTCTCCAATGGACATGATTCCCAAGTCATCCTGCTGCCTTTTTTCTTA
TAGACACAATGAACAGACCACCCACAACCTTAGTTCTCTAAGTCATCCTGCCTGCTGCCTTATTTCAC
AGTACATACATTTCTTAGGGACACAGTACACTGACCACATCACCACCCTCTTCTTCCAGTGCTGCGTG
GACCATCTGGCTGCCTTTTTTCTCCAAAAGATGCAATATTCAGACTGACTGACCCCCTGCCTTATTTC
ACCAAAGACACGATGCATAGTCACCCCGGCCTTGTTTCTCCAATGGCCGTGATACACTAGTGATCATG
TTCAGCCCTGCTTCCACCTGCATAGAATCTTTTCTTCTCAGACAGGGACAGTGCCGCCTCAACATCTC
CTGGGGTCTAGAAGCTGTTTCCTTTCCCCTCCTTCCTCCTCTTGCTCTAGCCTTAATACTGGCCTTTT
CCCTCCCTGCCCCAAGTGAAGACAGGGCACTCTGCGCCCACCACATGCACAGCTGTGCATGGAGACCT
GCAGGTGCACGTGCTGGAACACGTGTGGTTCCCCCCTGGCCCAGCCTCCTCTGCAGTGCCCCTCTCCC
CTGCCCATCCTCCCCACGGAAGCATGTGCTGGTCACACTGGTTCTCCAGGGGTCTGTGATGGGGCCCC
TGGGGGTCAGCTTCTGTCCCTCTGCCTTCTCACCTCTTTGTTCCTTTCTTTTCATGTATCCATTCAGT
TGATGTTTATTGAGCAACTACAGATGTCAGCACTGTGTTAGGTGCTGGGGGCCCTGCGTGGGAAGATA
AAGTTCCTCCCTCAAGGACTCCCCATCCAGCTGGGAGACAGACAACTAACTACACTGCACCCTGCG
NOV9k, 13376724
Protein Sequence	SEQ ID NO: 152	216 aa	MW
MWVQPWEHCGSASQEPWRSRSPEDPVVALVGTDATLRCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFT
EGRDQGSAYANRTALFPDLLAQGNASLRLQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPYSKPSMT
LEPNKDLRPGDTVTITCSSYQGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLFDVHSILRVVLGANG
TYSCLVRNPVLQ
NOV9l, 13376727	SEQ ID NO: 153	2650 bp
DNA Sequence	ORF Start: ATG at 62	ORF Stop: end of sequence
AGCTGTCAGCCGCCTCACAGGAAGATGCTGCGTCGGCGGGGCAGCCCTGGCATGGGTGTGCATGTGGG
TGCAGCCCTGGGAGCACTGTGGTTCTGCCTCACAGGAGCCCTGGAGGTCCAGGTCCCCTGAGGACCCG
GTGGTGGCCCTAGTGGGCACCGATGCCACCCTGCGCTGCTCCTTCTCCCCCGAGCCTGGCTTCAGCCT
GGCACAGCTCAACCTCATCTGGCAGCTGACAGACACCAAACAGCTCGTGCACAGTTTCACCGAAGGCC
GGGACCAGGGCAGCGCCTATGCCAACCGCACGGCCCTCTTCCCGGACCTGCTGGCACAAGGCAATGCA
TCCCTGAGGCTGCAGCGCGTGCGTGTGGCGGACGAGGGCAGCTTCACCTGCTTCGTGAGCATCCGGGA
TTTCGGCAGCGCTGCCGTCAGCCTGCAGGTGGCCGCTCCCTACTCGAAGCCCAGCATGACCCTGGAGC
CCAACAAGGACCTGCGGCCAGGGGACACGGTGACCATCACGTGCTCCAGCTACCAGGGCTACCCTGAG
GCTGAGGTGTTCTGGCAGGATGGGCAGGGTGTGCCCCTGACTGGCAACGTGACCACGTCGCAGATGGC
CAACGAGCAGGGCTTGTTTGATGTGCACAGCATCCTGCGGGTGGTGCTGGGTGCAAATGGCACCTACA
GCTGCCTGGTGCGCAACCCCGTGCTGCAGCAGGATGCGCACGGCTCTGTCACCATCACACCCCAGAGA
AGCCCCACAGGAGCCGTGGAGGTCCAGGTCCCTGAGGACCCGGTGGTGGCCCTAGTGGGCACCGATGC
CACCCTGCGCTGCTCCTTCTCCCCCGAGCCTGGCTTCAGCCTGGCACAGCTCAACCTCATCTGGCAGC
TGACAGACACCAAACAGCTGGTGCACAGTTTCACCGAAGGCCGGGACCAGGGCAGCGCCTATGCCAAC
CGCACGGCCCTCTTCCCGGACCTGCTGGCACAAGGCAATGCATCCCTGAGGCTGCAGCGCGTGCGTGT
GGCGGACGAGGGCAGCTTCACCTGCTTCGTGAGCATCCGGGATTTCGGCAGCGCTGCCGTCAGCCTGC
AGGTGGCCGCTCCCTACTCGAAGCCCAGCATGACCCTGGAGCCCAACAAGGACCTGCGGCCAGGGGAC
ACGGTGACCATCACGTGCTCCAGCTACCGGGGCTACCCTGAGGCTGAGGTGTTCTGGCAGGATGGGCA
GGGTGTGCCCCTGACTGGCAACGTGACCACGTCGCAGATGGCCAACGAGCAGGGCTTGTTTGATGTGC
ACAGCGTCCTGCGGGTGGTGCTGGGTGCGAATGGCACCTACAGCTGCCTGGTGCCCAACCCCGTGCTG
CAGCAGGATGCGCACGGCTCTGTCACCATCACAGGGCAGCCTATGACATTCCCCCCAGAGGCCCTGTG
GGTGACCGTGGGGCTGTCTGTCTGTCTCATTGCACTGCTGGTGGCCCTGGCTTTCGTGTGCTGGAGAA
AGATCAAACAGAGCTGTGAGGAGGAGAATGCAGGAGCTGAGGACCAGGATGGGGAGGGAGAAGGCTCC
AAGACAGCCCTGCAGCCTCTGAAACACTCTGACAGCAAAGAAGATGATGGACAAGAAATAGCCTGACC
ATGAGGACCAGGGAGCTGCTACCCCTCCCTACAGCTCCTACCCTCTGGCTGCAATGGGGCTGCACTGT
GAGCCCTGCCCCCAACAGATGCATCCTGCTCTGACAGGTGGGCTCCTTCTCCAAAGGATGCGATACAC
AGACCACTGTGCAGCCTTATTTCTCCAATGGACATGATTCCCAAGTCATCCTGCTGCCTTTTTTCTTA
TAGACACAATGAACAGACCACCCACAACCTTAGTTCTCTAAGTCATCCTGCCTGCTGCCTTATTTCAC
AGTACATACATTTCTTAGGGACACAGTACACTGACCACATCACCACCCTCTTCTTCCAGTGCTGCGTG
CACCATCTGGCTGCCTTTTTTCTCCAAAAGATGCAATATTCAGACTGACTGACCCCCTGCCTTATTTC
ACCAAAGACACGATGCATAGTCACCCCGGCCTTGTTTCTCCAATGGCCGTGATACACTAGTGATCATG
TTCAGCCCTGCTTCCACCTGCATAGAATCTTTTCTTCTCAGACAGGGACAGTGCGGCCTCAACATCTC
CTGGGGTCTAGAAGCTGTTTCCTTTCCCCTCCTTCCTCCTCTTGCTCTAGCCTTAATACTGGCCTTTT
CCCTCCCTGCCCCAAGTGAAGACAGGGCACTCTGCGCCCACCACATGCACAGCTGTGCATGGAGACCT
GCAGGTGCACGTGCTGGAACACGTGTGGTTCCCCCCTGGCCCAGCCTCCTCTCCAGTGCCCCTCTCCC
CTGCCCATCCTCCCCACGGAAGCATGTGCTGGTCACACTGGTTCTCCAGGGGTCTGTGATGGGGCCCC
TGGGGGTCAGCTTCTGTCCCTCTGCCTTCTCACCTCTTTGTTCCTTTCTTTTCATGTATCCATTCAGT
TGATGTTTATTGAGCAACTACAGATGTCAGCACTGTGTTAGGTGCTGGGGGCCCTGCGTGGGAAGATA
AAGTTCCTCCCTCAAGGACTCCCCATCCAGCTGGGAGACAGACAACTAACTACACTGCACCCTGCG
NOV9l, 13376727
Protein Sequence	SEQ ID NO: 154	522 aa	MW at 56436.7kD
MWVQPWEHCGSASQEPWRSRSPEDPVVALVGTDATLRCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFT
EGRDQGSAYANRTALFPDLLAQGNASLRLQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPYSKPSMT
LEPNKDLRPGDTVTITCSSYQGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLFDVHSILRVVLGANG
TYSCLVRNPVLQQDAHGSVTITPQRSPTGAVEVQVPEDPVVALVGTDATLRCSFSPEPGFSLAQLNLI
WQLTDTKQLVHSFTEGRDQGSAYANRTALFPDLLAQGNASLRLQRVRVADEGSFTCFVSIRDFGSAAV
SLQVAAPYSKPSMTLEPNKDLRPGDTVTITCSSYRGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLF
DVHSVLRVVLGANGTYSCLVRNPVLQQDAHGSVTITGQPMTFPPEALWVTVGLSVCLIALLVALAFVC
WRKIKQSCEEENAGAEDQDGEGEGSKTALQPLKHSDSKEDDGQEIA
NOV9m, 13376728	SEQ ID NO: 155	2650 bp
DNA Sequence	ORF Start: ATG at 62	ORF Stop: end of sequence
AGCTGTCAGCCGCCTCACAGGAAGATGCTGCGTCGGCGGGGCAGCCCTGGCATGGGTGTGCATGTGGG
TGCAGCCCTGGGAGCACTGTGGTTCTGCCTCACAGGAGCCCTGGAGGTCCAGGTCCCCTGAGGACCCG
GTGGTGGCCCTAGTGGGCACCGATGCCACCCTGCGCTGCTCCTTCTCCCCCGAGCCTGGCTTCAGCCT
GGCACAGCTCAACCTCATCTGGCAGCTGACAGACACCAAACAGCTGGTGCACAGTTTCACCGAAGGCC
GGGACCAGGGCAGCGCCTATGCCAACCGCACGGCCCTCTTCCCGGACCTGCTGGCACAAGGCAATGCA
TCCCTGAGGCTGCAGCGCGTGCGTGTCGCGGACGAGGGCAGCTTCACCTGCTTCGTGAGCATCCGGGA
TTTCGGCAGCGCTGCCGTCAGCCTGCAGGTGGCCGCTCCCTACTCGAAGCCCAGCATGACCCTGGAGC
CCAACAAGGACCTGCGGCCAGGGGACACGGTGACCATCACGTGCTCCAGCTACCAGGGCTACCCTGAG
GCTGAGGTGTTCTGGCAGGATGGGCAGGGTGTGCCCCTGACTGGCAACGTGACCACGTCGCAGATGGC
CAACGAGCAGGGCTTGTTTGATGTGCACAGCATCCTCCGGGTGGTGCTGGGTGCAAATCGCACCTACA
GCTGCCTGGTGCGCAACCCCGTGCTGCAGCAGGATGCGCACAGCTCTGTCACCATCACACCCCAGAGA
AGCCCCACAGGAGCCGTGGAGGTCCAGGTCCCTGAGGACCCGGTGGTGGCCCTAGTGGGCACCGATGC
CACCCTGCGCTGCTCCTTCTCCCCCGAGCCTGGCTTCAGCCTGGCACAGCTCAACCTCATCTGGCAGC
TGACAGACACCAAACAGCTGGTGCACAGTTTCACCGAAGGCCGGGACCAGGGCAGCGCCTATGCCAAC
CGCACGGCCCTCTTCCCGGACCTGCTGGCACAAGGCAATGCATCCCTGAGGCTGCAGCGCGTGCGTGT
GGCGGACGAGGGCAGCTTCACCTGCTTCGTGAGCATCCGGGATTTCGGCAGCGCTGCCGTCAGCCTGC
AGGTGGCCGCTCCCTACTCGAAGCCCAGCATGACCCTGGAGCCCAACAAGGACCTGCGGCCAGGGGAC
ACGGTGACCATCACGTGCTCCAGCTACCGGGGCTACCCTGAGGCTGAGGTGTTCTGGCAGGATGGGCA
GGGTGTGCCCCTGACTGGCAACGTGACCACGTCGCAGATGGCCAACGAGCAGGGCTTGTTTGATGTGC
ACAGCGTCCTGCGGGTGGTGCTGGGTGCGAATGGCACCTACAGCTGCCTGGTGCGCAACCCCGTGCTG
CAGCAGGATGCGCACGGCTCTGTCACCATCACAGGGCAGCCTATGACATTCCCCCCAGAGGCCCTGTG
GGTGACCGTGGGGCTGTCTGTCTGTCTCATTGCACTGCTGGTGGCCCTGGCTTTCGTGTGCTGGAGAA
AGATCAAACAGAGCTGTGAGGAGGAGAATGCAGGAGCTGAGCACCAGGATAGGGAGGGAGAAGGCTCC
AAGACAGCCCTGCAGCCTCTGAAACACTCTGACAGCAAAGAAGATCATGGACAAGAAATAGCCTGACC
ATGAGGACCAGGGAGCTGCTACCCCTCCCTACAGCTCCTACCCTCTGGCTGCAATGGGGCTGCACTGT
GAGCCCTGCCCCCAACAGATGCATCCTGCTCTGACAGGTGGGCTCCTTCTCCAAAGGATGCGATACAC
AGACCACTGTGCAGCCTTATTTCTCCAATGGACATGATTCCCAAGTCATCCTGCTGCCTTTTTTCTTA
TAGACACAATGAACAGACCACCCACAACCTTAGTTCTCTAAGTCATCCTGCCTGCTGCCTTATTTCAC
AGTACATACATTTCTTAGGGACACAGTACACTGACCACATCACCACCCTCTTCTTCCAGTGCTGCGTG
GACCATCTGGCTGCCTTTTTTCTCCAAAAGATGCAATATTCAGACTGACTGACCCCCTGCCTTATTTC
ACCAAAGACACGATGCATAGTCACCCCCGCCTTGTTTCTCCAATGGCCGTGATACACTAGTGATCATG
TTCAGCCCTGCTTCCACCTGCATAGAATCTTTTCTTCTCAGACAGGGACAGTGCGGCCTCAACATCTC
CTGGGGTCTAGAAGCTGTTTCCTTTCCCCTCCTTCCTCCTCTTGCTCTAGCCTTAATACTGGCCTTTT
CCCTCCCTGCCCCAAGTGAAGACAGGGCACTCTGCGCCCACCACATGCACAGCTGTGCATGGAGACCT
GCAGGTGCACGTGCTGGAACACGTGTGGTTCCCCCCTGGCCCAGCCTCCTCTGCAGTGCCCCTCTCCC
CTGCCCATCCTCCCCACGGAAGCATGTGCTGGTCACACTGGTTCTCCAGGGGTCTGTGATGGGGCCCC
TGGGGGTCAGCTTCTGTCCCTCTGCCTTCTCACCTCTTTGTTCCTTTCTTTTCATGTATCCATTCAGT
TGATGTTTATTGAGCAACTACAGATGTCAGCACTGTGTTAGGTGCTGCGGGCCCTGCGTGGGAAGATA
AAGTTCCTCCCTCAAGGACTCCCCATCCAGCTGGGAGACAGACAACTAACTACACTGCACCCTGCG
NOV9m, 13376728
Protein Sequence	SEQ ID NO: 156	522 aa	MW at 56436.7kD
MWVQPWEHCGSASQEPWRSRSPEDPVVALVGTDATLRCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFT
EGRDQGSAYANRTALFPDLLAQGNASLRLQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPYSKPSMT
LEPNKDLRPGDTVTITCSSYQGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLFDVHSILRVVLGANG
TYSCLVRNPVLQQDAHSSVTITPQRSPTGAVEVQVPEDPVVALVGTDATLRCSFSPEPGFSLAQLNLI
WQLTDTKQLVHSFTEGRDQGSAYANRTALFPDLLAQGNASLRLQRVRVADEGSFTCFVSIRDFGSAAV
SLQVAAPYSKPSMTLEPNKDLRPGDTVTITCSSYRGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLF
DVHSVLRVVLGANGTYSCLVRNPVLQQDAHGSVTITGQPMTFPPEALWVTVGLSVCLIALLVALAFVC
WRKIKQSCEEENAGAEDQDREGEGSKTALQPLKHSDSKEDDGQEIA

[0427] A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 9B.

TABLE 9B
Comparison of the NOV9 protein sequences.
NOV9a ------------------------------------------------------------
NOV9b ----------------------MTLEPNKDLRPGDTVTITCSSYQGYPEAEVFWQDGQGV
NOV9c ------------------------------------------------------------
NOV9d ------------------------------------------------------------
NOV9e MLRRRGSPGMGVHVGAALGALWFCLTGALEVQVPEDPVVALVGTDATLCCSFSPEPGFSL
NOV9f ------------------------------------------------------------
NOV9g ------------------------------------------------------------
NOV9a ----------------------------------------------MWVQPWEHCGSASQ
NOV9b PLTGNVTTSQMANEQGLFDVHSILRVVLGANGTYSCLVRNPVLQQDAHSSVTITPQRSPT
NOV9c ----------------------------------------------MWVQPWEHCGSASQ
NOV9d ------------------------------------------------------------
NOV9e AQLNLIWQLTDTKQLVHSFAEGQDQGSAYANRTALFPDLLAQGNASLRLQRVRVADEGSF
NOV9f ------------------------------------------------------------
NOV9g ------------------------------------------------------------
NOV9a EPWRSRSPEDPVVALVGTDATLRCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFTEGRDQG
NOV9b GAVEVQVPEDPVVALVGTDATLRCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFTEGRDQG
NOV9c EPWRSRSPEDPVVALVGTDATLRCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFTEGRDQG
NOV9d ------------------------------------------------------------
NOV9e TCFVSIRDFGSAAVSLQVAAPYSKPSMTLEPNKDLRPGDTVTITCSSYQGYPEAEVFWQD
NOV9f ------------------------------------------------------------
NOV9g -ALEVQVPEDPVVALVGTDATLCCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFAEGQDQG
NOV9a SAYANRTALFPDLLAQGNASLRLQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPYSKPS
NOV9b SAYANRTALFPDLLAQGNASLRLQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPYSKPS
NOV9c SAYANRTALFPDLLAQGNASLRLQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPYSKPS
NOV9d --------------------------------------MLRRRGSPGMGVHVGAALGALW
NOV9e GQGVPLTGNVTTSQMANEQGLFDVHSILRVVLGANGTYSCLVRNPVLQQDAHSSVTITPQ
NOV9f ------------------------------------------------------------
NOV9g SAYANRTALFPDLLAQGNASLRLQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPYSKPS
NOV9a MTLEPNKDLRPGDTVTITCSSYQGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLFDVHS
NOV9b MTLEPNKDLRPGDTVTITCSSYQGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLFDVHS
NOV9c MTLEPNKDLRPGDTVTITCSSYQGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLFDVHS
NOV9d FCL---------------------------------------------------------
NOV9e RSP---------------------------------------------------------
NOV9f ------------------------------------------------------------
NOV9g MTLEPNKDLRPGDTVTITCSSYQGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLFDVHS
NOV9a ILRVVLGANGTYSCLVRNPVLQQDAHSSVTITPQRSPTGAVEVQVPEDPVVALVGTDATL
NOV9b ILRVVLGANGTYSCLVRNPVLQQDAHSSVTITPQRSPTGAVEVQVPEDPVVALVGTDATL
NOV9c ILRVVLGANGTYSCLVRNPVLQQDAHSSVTITPQRSPTGAVEVQVPEDPVVALVGTDATL
NOV9d -------------------------------------TGALEVQVPEDPVVALVGTDATL
NOV9e -------------------------------------TGAVEVQVPEDPVVALVGTDATL
NOV9f ---------------------------------------ALEVQVPEDPVVALVGTDATL
NOV9g ILRVVLGANGTYSCLVRNPVLQQDAHGSVTITPQRSPTGAVEVQVPEDPVVALVGTDATL
NOV9a RCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFTEGRDQGSAYANRTALFPDLLAQGNASLR
NOV9b RCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFTEGRDQGSAYANRTALFPDLLAQGNASLR
NOV9c RCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFTECRDQGSAYANRTALFPDLLAQGNASLR
NOV9d CCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFAEGQDQGSAYANRTALFPDLLAQGNASLR
NOV9e RCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFTEGRDQGSAYANRTALFPDLLAQGNASLR
NOV9f CCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFAEGQDQGSAYANRTALFPDLLAQGNASLR
NOV9g RCSFSPEPGFSLAQLNLIWQLTDTKQLVHSFTEGRDQGSAYANRTALFPDLLAQGNASLR
NOV9a LQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPYSKPSMTLEPNKDLRPGDTVTITCSSY
NOV9b LQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPYSKPSMTLEPNKDLRPGDTVTITCSSY
NOV9c LQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPYSKPSMTLEPNKDLRPGDTVTITCSSY
NOV9d LQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPYSKPSMTLEPNKDLRPGDTVTITCSSY
NOV9e LQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPYSKPSMTLEPNKDLRPGDTVTITCSSY
NOV9f LQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPYSKPSMTLEPNKDLRPGDTVTITCSSY
NOV9g LQRVRVADEGSFTCFVSIRDFGSAAVSLQVAAPYSKPSMTLEPNKDLRPGDTVTITCSSY
NOV9a RGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLFDVHSVLRVVLGANGTYSCLVRNPVLQ
NOV9b RGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLFDVHSVLRVVLGANGTYSCLVRNPVLQ
NOV9c RGYPEAERPAG-GAGCEWHLQLPGAQPR------AAAGCARLCHHHGAAYDIPPRGPVGD
NOV9d RGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLFDVHSVLRVVLGANGTYSCLVRNPVLQ
NOV9e RGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLFDVHSVLRVVLGANGTYSCLVRNPVLQ
NOV9f RGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLFDVHSVLRVVLGANGTYSCLVRNPVLQ
NOV9g RGYPEAEVFWQDGQGVPLTGNVTTSQMANEQGLFDVHSVLRVVLGANGTYSCLVRNPVLQ
NOV9a QDAHGSVTITGQPMTFPPEALWVTVGLSVCLIALLVALAFVCWRKIKQSCEEENAGAEDQ
NOV9b QDAHGSVTITGQPMTFPPEALWVTVGLSVCLIALLVALAFVCWRKIKQSCEEENAGAEDQ
NOV9c RGAVCLSHCTAGGPGFRVLEKDQTEL----------------------------------
NOV9d QDAHGSVTITGQPMTFPPEALWVTVGLSVCLIALLVALAFVCWRKIKQSCEEENAGAEDQ
NOV9e QDAHGSVTITGQPMTFPPEALWVTVGLSVCLIALLVALAFVCWRKIKQSCEEENAGAEDQ
NOV9f QDAHGSVTITGQPMTF--------------------------------------------
NOV9g QDAHGSVTITGQPMTF--------------------------------------------
NOV9a DGEGEGSKTALQPLKHSDSKEDDGQEIA
NOV9b DGEGEGSKTALQPLKHSDSKEDDGQEIA
NOV9c ----------------------------
NOV9d DGEGEGSKTALQPLKHSDSKEDDGQEIA
NOV9e DGEGEGSKTALQPLKHSDSKEDDGQEIA
NOV9f ----------------------------
NOV9g ----------------------------
NOV9a (SEQ ID NO: 132)
NOV9b (SEQ ID NO: 134)
NOV9c (SEQ ID NO: 136)
NOV9d (SEQ ID NO: 138)
NOV9e (SEQ ID NO: 140)
NOV9f (SEQ ID NO: 142)
NOV9g (SEQ ID NO: 144)

[0428] Further analysis of the NOV9a protein yielded the following properties shown in Table 9C.

TABLE 9C
Protein Sequence Properties NOV9a
SignalP	No Known Signal Sequence Predicted
analysis:
PSORT II	PSG: a new signal peptide prediction method
analysis:	N-region: length 7; pos. chg 0; neg. chg 1
	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): −5.53
	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: 1
	Number of TMS(s) for threshold 0.5: 1
	INTEGRAL	Likelihood =	−12.15	Transmembrane 459-475
	PERIPHERAL	Likelihood =	−13.45 (at 194)
	ALOM score: −12.15 (number of TMSs: 1)
	MTOP: Prediction of membrane topology (Hartmann et al.)
	Center position for calculation: 466
	Charge difference: 0.0 C(−1.0)-N(−1.0)
	N >= C: N-terminal side will be inside
	>>> Single TMS is located near the C-terminus
	>>> membrane topology: type Nt (cytoplasmic tail 1 to 458)
	MITDISC: discrimination of mitochondrial targeting seq
	R content:	0	Hyd Moment (75):	4.94
	Hyd Moment(95):	7.42	G content:	1
	D/E content:	2	S/T content:	2
	Score:	−6.93
	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: 6.9%
	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: too long tail
	Dileucine motif in the tail: found
	LL at 87
	LL at 305
	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):
	26.1%: nuclear
	21.7%: cytoplasmic
	13.0%: mitochondrial
	13.0%: Golgi
	13.0%: endoplasmic reticulum
	8.7%: vesicles of secretory system
	4.3%: peroxisomal
	>> prediction for CG59538-01 is nuc (k = 23)

[0429] 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	Identities/
		Residues/	Similarities
Geneseq	Protein/Organism/Length	Match	for the	Expect
Identifier	[Patent #, Date]	Residues	Matched Region	Value
AAU81009	B7-related protein, BSL2-4616811 -	22 . . . 522	498/501 (99%)	0.0
	Homo sapiens, 534 aa.	34 . . . 534	499/501 (99%)
	[WO200194413-A2, 13 DEC. 2001]
AAU80025	Human dendritic cell wall	22 . . . 522	498/501 (99%)	0.0
	membrane molecule - Homo	34 . . . 534	499/501 (99%)
	sapiens, 534 aa. [WO200222683-
	A1, 21 MAR. 2002]
AAB27250	Human amyloid precursor protein	22 . . . 522	498/501 (99%)	0.0
	protease SEQ ID NO: 4 - Homo	34 . . . 534	499/501 (99%)
	sapiens, 534 aa. [WO200068266-
	A1, 16 NOV. 2000]
AAU00906	Human B lymphocyte activation	22 . . . 522	498/501 (99%)	0.0
	antigen A7, BLAA#3 - Homo	34 . . . 534	499/501 (99%)
	sapiens, 534 aa. [WO200118204-
	A1, 15 MAR. 2001]
AAB88459	Human membrane or secretory	22 . . . 522	497/501 (99%)	0.0
	protein clone PSEC0249 - Homo	34 . . . 534	498/501 (99%)
	sapiens, 534 aa. [EP1067182-A2,
	10 JAN. 2001]

[0430] In a BLAST search of public sequence databases, the NOV9a protein was found to have homology to the proteins shown in the BLASTP data in Table 9E.

TABLE 9E
Public BLASTP Results for NOV9a
		NOV9a	Identities/
Protein		Residues/	Similarities
Accession		Match	for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
CAC18949	Sequence 3 from Patent	22 . . . 522	498/501	(99%)	0.0
	WO0068266 - Homo sapiens	34 . . . 534	499/501	(99%)
	(Human), 534 aa.
Q8NBI8	Hypothetical protein	22 . . . 522	497/501	(99%)	0.0
	NT2RP3001861 - Homo sapiens	34 . . . 534	498/501	(99%)
	(Human), 534 aa.
Q8NCB6	Hypothetical protein FLJ90368 -	22 . . . 515	489/494	(98%)	0.0
	Homo sapiens (Human), 533 aa.	34 . . . 527	490/494	(98%)
CAC18948	Sequence 1 from Patent	22 . . . 522	471/501	(94%)	0.0
	WO0068266 - Homo sapiens	34 . . . 534	472/501	(94%)
	(Human), 534 aa.
Q8NC34	Hypothetical protein FLJ90516 -	135 . . . 522	388/388	(100%)	0.0
	Homo sapiens (Human), 388 aa.	1 . . . 388	388/388	(100%)

[0431] PFam analysis predicts that the NOV9a protein contains the domains shown in the Table 9F.

TABLE 9F
Domain Analysis of NOV9a
Pfam	NOV9a	Identities/Similarities	Expect
Domain	Match Region	for the Matched Region	Value
ig	31 . . . 112	17/83 (20%)	7.2e−07
		59/83 (71%)
ig	146 . . . 210	18/68 (26%)	0.00014
		47/68 (69%)
ig	249 . . . 330	17/83 (20%)	7.2e−07
		59/83 (71%)
ig	364 . . . 428	17/68 (25%)	0.00062
		47/68 (69%)

[0432] The NOV10 clone was analyzed, and the nucleofide and encoded polypeptide sequences are shown in Table 10A.

TABLE 10A
NOV10 Sequence Analysis
NOV10a,CG59932-01	SEQ ID NO: 157	1171 bp
DNA Sequence	ORF Start: at 2	ORF Stop: end of sequence
GGAGGCCGCAAGGCCCTTCGCCCGGCAGTGGAGGGCCCAGTCCCTACCCCTGGCAGTAGGGGGCGTTT
TGAAGCTGCGGCTCTGTGAGCTGTGGCTACTGCTACTGGGTTCTAGTTTGAACGCCAGATTTTTGCCA
GACGAGGAGGACGTAGACTTTATCAACGAGTACGTGAACCTCCACAATGAGCTGCGGGGCGACGTTAT
TCCCCGAGGGTCTAACTTGCGCTTCATGACTTGGGATGTAGCTTTATCACGGACTGCTAGAGCATGGG
GAAAAAAATGTTTGTTTACGCATAATATTTATTTACAAGATGTACAAATGGTCCATCCTAAATTTTAT
GGTATTGGTGAAAATATGTGGGTCGGCCCTGAAAATGAATTTACTGCAAGTATTGCTATCAGAAGTTG
GCATGCAGAGAACAAAATGTACAATTTTGAAAATGGCAGTTGCTCTGGAGACTGTTCTAATTATATTC
AGCTTGTTTGGGACCACTCTTACAAAGTTGGTTGTGCTGTTACTCCATGTTCAAAAATTGGACATATT
ATACATGCAGCAATTTTCATATGCAACTATGCGCCAGGAGGAACACTGACCAGAAGACCTTATGAACC
AGGAATATTTTGTACTCGATGTGGCAGACGTGACAAATGCACAGATTTTCTATGCAGTAATGCAGATC
GTGACCAAGCCACATATTACCGATTTTGGTATCCAAAATGGGAAATGCCCCGGCCAGTTGTGTGTGAT
CCACTGTGCACATTCATTTTATTATTGAGAATATTATGTTTTATCCTGTGTGTCATAACTGTTTTGAT
AGTACAGTCTCAGTTTCCAAATATCTTGTTGGAACAACAAATGATATTTACCCCTGAGCAATCTGAAG
CAGGGAATGAAGAGGAGGAAAAAGAGGAAGAGAAGAAAGAGAAAGAGGAAATGGAAATGGAAATAATG
GAAATGGAGGAGGAAAAAGAAGAGAGAGAGGAGGAGGAGGAGGAAACACAAAAAGAAAAGATGGAGGA
AGAGGAAAAATAAGAGTAGAAAGAGGAGGAAAAAGATGTATCACCAATATAAACCAAAAGTGTAATAC
AAAAAAAGACAGAAAAAAAAAAAAAGTAAAACACTGAGTTTTAACAAGAAAGAAAATATCCAAACCAC
CATTGGAATGTTTTT
NOV10a, CG59932-01
Protein Sequence	SEQ ID NO: 158	343 aa	MW at 40047.3kD
EAARPFAREWRAQSLPLAVGGVLKLRLCELWLLLLGSSLNARFLPDEEDVDFINEYVNLHNELRGDVI
PRGSNLRFMTWDVALSRTARAWGKKCLFTHNIYLQDVQMVHPKFYGIGENMWVGPENEFTASIAIRSW
HAEKKMYNFENGSCSGDCSNYIQLVWDHSYKVGCAVTPCSKIGHIIHAAIFICNYAPGGTLTRRPYEP
GIFCTRCGRRDKCTDFLCSNADRDQATYYRFWYPKWEMPRPVVCDPLCTFILLLRILCFILCVITVLI
VQSQFPNILLEQQMIFTPEESEAGNEEEEKEEEKKEKEEMEMEIMEMEEEKEEREEEEEETQKEKMEE
EEK

[0433] Further analysis of the NOV10a protein yielded the following properties shown in Table 10B.

TABLE 10B
Protein Sequence Properties NOV10a
SignalP	Cleavage site between residues 42 and 43
analysis:
PSORT II	PSG: a new signal peptide prediction method
analysis:	N-region: length 11; pos. chg 3; neg. chg 2
	H-region: length 12; peak value 7.44
	PSG score: 3.04
	GvH: von Heijne's method for signal seq. recognition
	GvH score (threshold: −2.1): −0.10
	possible cleavage site: between 41 and 42
	>>> Seems to have a cleavable signal peptide (1 to 41)
	ALOM: Klein et al's method for TM region allocation
	Init position for calculation: 42
	Tentative number of TMS(s) for the threshold 0.5: 1
	Number of TMS(s) for threshold 0.5: 1
	INTEGRAL	Likelihood =	−13.43	Transmembrane 257-273
	PERIPHERAL	Likelihood =	−12.70 (at 172)
	ALOM score: −13.43 (number of TMSs: 1)
	MTOP: Prediction of membrane topology (Hartmann et al.)
	Center position for calculation: 20
	Charge difference: −1.0 C(1.0)-N(2.0)
	N >= C: N-terminal side will be inside
	>>> membrane topology: type 1a (cytoplasmic tail 274 to 343)
	MITDISC: discrimination of mitochondrial targeting seq
	R content:	4	Hyd Moment(75):	9.56
	Hyd Moment(95):	18.17	G content:	2
	D/E content:	3	S/T content:	1
	Score:	−4.20
	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: 11.4%
	NLS Score: −0.47
	KDEL: ER retention motif in the C-terminus: none
	ER Membrane Retention Signals:
	XXRR-like motif in the N-terminus: AARP
	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 281
	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
	290 E	1.00
	291 E	1.00
	292 S	1.00
	293 E	1.00
	294 A	1.00
	295 G	1.00
	296 N	1.00
	297 E	1.00
	298 E	1.00
	299 E	1.00
	300 E	1.00
	301 K	1.00
	302 E	1.00
	303 E	1.00
	304 E	1.00
	305 K	1.00
	306 K	1.00
	307 E	1.00
	308 K	1.00
	309 E	1.00
	310 E	1.00
	311 M	1.00
	312 E	1.00
	313 M	1.00
	314 E	1.00
	315 I	1.00
	316 M	1.00
	317 E	1.00
	318 M	1.00
	319 E	1.00
	320 E	1.00
	321 E	1.00
	322 K	1.00
	323 E	1.00
	324 E	1.00
	325 R	1.00
	326 E	1.00
	327 E	1.00
	328 E	1.00
	329 E	1.00
	330 E	1.00
	331 E	1.00
	332 T	1.00
	333 Q	1.00
	334 K	1.00
	335 E	1.00
	336 K	1.00
	337 M	1.00
	338 E	1.00
	339 E	1.00
	340 E	1.00
	341 E	1.00
	342 K	1.00
	total: 53 residues
	Final Results (k = 9/23):
	55.6%: endoplasmic reticulum
	22.2%: Golgi
	11.1%: plasma membrane
	11.1%: extracellular, including cell wall
	>> prediction for CG59932-01 is end (k = 9)

[0434] A search of the NOV10a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 10C.

TABLE 10C
Geneseq Results for NOV10a
		NOV10a	Identities/
		Residues/	Similarities
Geneseq	Protein/Organism/Length	Match	for the	Expect
Identifier	[Patent #, Date]	Residues	Matched Region	Value
ABP69108	Human polypeptide SEQ ID NO	1 . . . 223	220/223	(98%)	e−134
	1155 - Homo sapiens, 253 aa.	2 . . . 224	222/223	(98%)
	[WO200270539-A2, 12 SEP. 2002]
AAB64953	Human secreted protein sequence	45 . . . 222	177/178	(99%)	e−109
	encoded by gene 12 SEQ ID NO: 131 -	1 . . . 178	177/178	(99%)
	Homo sapiens, 178 aa.
	[WO200076530-A1, 21 DEC. 2000]
AAB43408	Human cancer associated protein	38 . . . 282	102/250	(40%)	6e−51
	sequence SEQ ID NO: 853 - Homo	55 . . . 300	143/250	(56%)
	sapiens, 302 aa. [WO200055350-A1,
	21 SEP. 2000]
ABB53121	Human ORF27 protein - Homo	94 . . . 178	85/85	(100%)	2e−48
	sapiens, 85 aa. [WO200177155-A2,	1 . . . 85	85/85	(100%)
	18 OCT. 2001]
AAE18962	Mouse testes-specific, vespid and	37 . . . 282	96/247	(38%)	1e−46
	sp, 255 aa. [WO200206344-A2, 24	18 . . . 253	138/247	(55%)
	JAN. 2002]

[0435] In a BLAST search of public sequence databases, the NOV10a protein was found to have homology to the proteins shown in the BLASTP data in Table 10D.

TABLE 10D
Public BLASTP Results for NOV10a
		NOV10a	Identities/
Protein		Residues/	Similarities
Accession		Match	for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
Q8NA43	Hypothetical protein FLJ35856 -	1 . . . 228	228/228	(100%)	e−139
	Homo sapiens (Human), 229 aa.	2 . . . 229	228/228	(100%)
Q8N6N0	Similar to RIKEN cDNA	1 . . . 223	223/223	(100%)	e−135
	4921508O11 gene - Homo sapiens	2 . . . 224	223/223	(100%)
	(Human), 253 aa.
Q9CQ35	4921508O11Rik protein - Mus	1 . . . 343	209/345	(60%)	e−117
	musculus (Mouse), 332 aa.	2 . . . 331	252/345	(72%)
P48060	Glioma pathogenesis-related	38 . . . 282	103/250	(41%)	9e−52
	protein (GliPR) (RTVP-1 protein) -	19 . . . 264	144/250	(57%)
	Homo sapiens (Human), 266 aa.
JC5308	testis-specific, vespid, and	38 . . . 282	103/250	(41%)	1e−51
	pathogenesis-related protein 1	19 . . . 264	144/250	(57%)
	precursor - human, 266 aa.

[0436] PFam analysis predicts that the NOV10a protein contains the domains shown in the Table 10E.

TABLE 10E
Domain Analysis of NOV10a
Pfam	NOV10a Match	Identities/Similarities	Expect
Domain	Region	for the Matched Region	Value
SCP	57 . . . 190	42/167 (25%)	3.1e−33
		95/167 (57%)

Example 11. NOV 11, CG94562: Novel Agrin-like protein with EGF and laminin G domains.

[0437] The NOV11 clone was analyzed, and the nucleotide and encoded polypeptide sequences are shown in Table 11A.

TABLE 11A
NOV11 Sequence Analysis
NOV11a, CG94562-01	SEQ ID NO: 159	3124 bp
DNA Sequence	ORF Start: ATG at 5	ORF Stop: end of sequence
CCAAATGCCTGGCCACCCTTCAACATGCTCTCCCCACAGCGGCTACCCAAAAGCCAGGCACAGATCCC
ATCTTCCACCCGGTCCAGTCCCTCCTCCTCAGAACAGCAACGGGGCCAGCTGCCAAGTGTCAGGGAGC
ATGTGGAAGGAGGGCAAGGGGAAGAGAGGGCACCGCATTGCGATGGGGGAGGGCGGGTGCTGCTCGGG
CTCTGAGCTCTGTTCTGAGAATGGGAAGACATCAGAATGCCAGAATTCAGAAACAGAAGTACAAGAAC
AAAAAGTTTCCTCACTGGGAAGTGGAAGAATGGAGGAAGGGAATGACCAGAAAGATCCAGGAGAGGTT
CTGGGCTCATCAGCCCTCCTCCCGAGATCGTGCCACTGCACTCCAGCCTGGGAGACAGAGCGGGACTC
CGTCTCATTAAAAAAAAAAAATGTGGTTACTAAACAAGATAGAACAAAAATACCAAAATCAAAAGGGA
GAAGAAAATTTCCCACCGTAACAGGAGAAAAGGCTTCTCCTGTCCTGGTGGGTCTTGCAGGTGGGACA
GACAGGAGCAGTGGAATCTGTGATGAGGCCTCGTGCATCCATGGTGGCACCTGCACAGCAATCAAAGC
CGACTCCTACATTTGCCTCTGTCCCCTTGGGTTTAAAGGTCGACACTGTGAAGATATTCCTCAGTTCA
GAGAGTCTCTGAGATCTTACGCTGCAACTCCCTGGCCACTGGAGCCCCAGCATTACCTTTCCTTCATC
GAATTTGAGATCACATTTCGGCCAGACTCAGGAGATGGTGTCCTCCTGTACAGCTATGACACAGGCAG
CAAAGACTTCCTGTCCATCAACTTGGCAGGGGGCCACGTGGAGTTCCGCTTTGACTGTGGCTCTGGGA
CCGGTGTCCTCAGGAGTGAGACCAAAATCAAACTAGGGGGTTGGCACACGGTTATGCTCTACAGAGAT
GGGCTGAACGGGCTGCTGCAGCTGAACAATGGCACCCCAGTGACAGGCCAGTCTCAGGGCCAATACAG
TAAAATTACTTTCCGGACACCTCTCTATCTTGGTGGCGCTCCCAGCGCTTACTGGTTGGTTAGAGCAA
CAGCGACAAACCGAGGCTTTCAAGGCTGTGTGCAGTCGCTCGCTGTGAATGGGAGGAGAATTGACATG
AGGCCCTGGCCCCTGGGAAAAGCACTCAGTGGGGCTGATGTGGGGGAATGCAGCAGTGGAATCTGTGA
TGAGGCCTCGTGCATCCATGGTGGCACCTGCACAGCAATCAAAGCCGACTCCTACATTTGCCTCTGTC
CCCTTGGGTTTAAAGGTCGACACTGTGAAGATGCTTTCACCTTGACCATTCCTCAGTTCAGAGAGTCT
CTGAGATCTTACGCTGCAACTCCCTGGCCACTGGAGCCCCAGCATTACCTTTCCTTCATGGAATTTGA
GATCACATTTCGGCCAGACTCAGGAGATGGTGTCCTCCTGTACAGCTATGACACAGGCAGCAAAGACT
TCCTGTCCATCAACTTGGCAGGGGGCCACGTGGAGTTCCGCTTTGACTGTGGCTCTGGGACCGGTGTC
CTCAGGAGTGAAGATCCCCTCACCCTGGGCAACTGGCACGAGCTTCGTGTATCTCGCACAGCAAAGAA
TGGAATCTTACAGGTGGATAAGCAGAAGATAGTGGAGGGAGTGGCAGAGGGAGGCTTCACACAGATTA
AGTGCAACACAGACATTTTCATTGGCGGAGTCCCCAATTATGATGATGTGAAGAAGAACTCGGGTGTC
CTGAAGCCTTTCAGCGGGAGCATCCAGAAGATCATCCTGAATGACCGAACCATCCATGTGAAGCATGA
CTTCACCTCCGGAGTGAATGTGGAGAATGCGGCCCACCCCTGTGTGAGAGCCCCTTGTGCCCATGGGG
GCAGCTGCCGGCCCAGGAAGGAGGGCTATGACTGTGACTGCCCCTTGGGCTTTGAGGGGCTTCACTGC
CAGAAAGGTACGCTCAGGGGTCTGAGGCACAGCTCCCTGGAGGGAGTCGAAGGAACCGACAGCCAATT
GGGGGACCACAACAAGTACTTGATTGTGCCCAGAAAAGAGAACCGAAACAGAAGCTCAGCTGTGGGTG
GGATGGTCCAACTTCCCCCTAAACTGCCAGCTGAATCTATTCACCACCCATTCTACTCCAGTAGGGAA
ACAGCTCCCACCAGCTCCCATGCCCAGCCCTGGAGAGCCCCCTCCAAACACAGGTCGCATTCTTTACC
CCACTGTGCATGGATTTACTGGTGCTCAAGAGCTCCCTTGCACTATCATACATTTACTAATAATCAGG
ACACCAATATTTTATCTTCCACAGTTTCAGAAACATACTCTTCCACTGAGCTGAGACAAACTCCCTCT
GGCTCAAATCAGATTTCTACAATAAATAAAATGCTCCCTCATTCTTCTCCCAGTGAAGGTAACCACTC
TTCTTGGTCATTTATGATTATATACACGAGGGAGCTTTTCCAGGGTGAGTATCAGCACGTCAGAGGAA
GCGGGAGGTTCTTTGGAGGGTCTGAATCCAGGGTGTCAGGATCAAGATCAAATGTGTTCATGAGGTTT
AAAACAACTGCCAAGGATGGCCTTTTGCTGTGGAGGGGAGACAGCCCCATGAGACCCAACAGCGACTT
CATTTCCTTGGGCCTTCGGGATGGAGCCCTCGTGTTCAGGTATAACCTGGGCAGTGGTGTGGCATCCA
TCATGGTGAATGGCTCCTTCAACGATGGTCGGTGGCACCGAGTTAACGCCGTTAGGAGGGATGGCCAG
TCAGGAAAGATAACCGTGGATGACTATGGAGCCAGAACAGGCAAATCCCCAGGCATGATGCGGCAGCT
TAACATCAATGGAGCTCTGTATGTGGGTAAGGAATGAAGGAAATTGCTCTCCACACTAACAGGCAATA
TATGAGAGGGCTCGTGGGCTGTATCTCTCACTTCACCCTGTCCACCGATTACCACATTTCCCTCGTGG
AAGATGCCGTGGATGGGAAAAACATCAACACTTGTGGAGCCAAGTAACACCAGCTGGCCTTGTCCAAG
GGACAGAGCCTTCTATTCTGAGAATCCCAGGGGCCCTCAGACCCTGCCTGATGCTATATGCAGA
NOV11a, CG94562-01
Protein Sequence	SEQ ID NO: 160	962 aa	MW at 105031.1kD
MPGQPSTCSPHSGYPKARHRSHLPAGPVPPPQNSNGASCQVSGSMWKEGKGKRGHRIAMGEGGCCSGS
ELCSENGKTSECQNSETEVQEQKVSSLGSGRMEEGNDQKDPGEVLGSSALLPRSCHCTPAWETERDSV
SLKKKNVVTKQDRTKIPKSKGRRKFPTVTGEKASPVLVGLAGGTDRSSGICDEASCIHGGTCTAIKAD
SYICLCPLGFKGRHCEDIPQFRESLRSYAATPWPLEPQHYLSFMEFEITFRPDSGDGVLLYSYDTGSK
DFLSINLAGGHVEFRFDCGSGTGVLRSETKIKLGGWHTVMLYRDGLNGLLQLNNGTPVTGQSQGQYSK
ITFRTPLYLGGAPSAYWLVRATGTNRGFQGCVQSLAVNGRRIDMRPWPLGKALSGADVGECSSGICDE
ASCIHGGTCTAIKADSYICLCPLGFKGRHCEDAFTLTIPQFRESLRSYAATPWPLEPQHYLSFMEFEI
TFRPDSGDGVLLYSYDTGSKDFLSINLAGGHVEFRFDCGSGTGVLRSEDPLTLGNWHELRVSRTAKNG
ILQVDKQKIVEGVAEGGFTQIKCNTDIFIGGVPNYDDVKKNSGVLKPFSGSIQKIILNDRTIHVKHDF
TSGVNVENAAHPCVRAPCAHGGSCRPRKEGYDCDCPLGFEGLHCQKGTLRGLRHSSLEGVEGTDSQLG
DHNKYLIVPRKENRNRSSAVGGMVQLPPKLPAESIHHPFYSSRETAPTSSHAQPWRAPSKHRSHSLPH
CAWIYWCSRAPLHYHTFTNNQDTNILSSTVSETYSSTELRQTPSGSNQISTINKMLPHSSPSEGNHSS
WSFMIIYTRELFQGEYQHVRGSGRFFGGSESRVSGSRSNVFMRFKTTAKDGLLLWRGDSPMRPNSDFI
SLGLRDGALVFRYNLGSGVASIMVNGSFNDGRWHRVKAVRRDGQSGKITVDDYGARTGKSPGMMRQLN
INGALYVGKE
NOV11b, 209886403	SEQ ID NO: 161	660 bp
DNA Sequence	ORF Start: at 1	ORF Stop: at 661
GGATCCGCACTCAGTGGGGCTGATGTGGGGGAATGCAGCAGTGGAATCTGTGATGAGGCCTCGTGCAT
CCATGGTGGCACCTGCACAGCAATCAAAGCCGACTCCTACATTTGCCTCTGTCCCCTTGGGTTTAAAG
GTCGACACTGTGAAGATGCTTTCACCTTGACCATTCCTCAGTTCAGAGAGTCTCTGAGATCTTACGCT
GCAACTCCCTGGCCACTGCAGCCCCAGCATTACCTTTCCTTCATGGAATTTGACATCACATTTCGGCC
AGACTCAGGAGATGGTGTCCTCCTGTACAGCTATGACACAGGCAGCAAAGACTTCCTGTCCATCAACT
TGGCAGGGGGCCACGTGGAGTTCCGCTTTGACTGTGGCTCTGGGACCGGTGTCCTCAGGAGTGAAGAT
CCCCTCACCCTGGGCAACTGGCACGAGCTTCGTGTATCTCGCACAGCAAAGAATGGAATCTTACAGGT
GGATAAGCAGAAGATAGTGGAGGGAATGGCAGAGGGAGGCTTCACACAGATTAAGTGCAACACAGACA
TTTTCATTGGCGGAGTCCCCAATTATGATCATGTGAAGAAGAACTCGGGTGTCCTGAAGCCTTTCAGC
GGGAGCATCCAGAAGATCATCCTGAATGACCGAACCATCCATCTCGAG
NOV11b, 209886403
Protein Sequence	SEQ ID NO: 162	220 aa	MW at 23939.7kD
GSALSGADVGECSSGICDEASCIHGGTCTAIKADSYICLCPLGFKGRHCEDAFTLTIPQFRESLRSYA
ATPWPLEPQHYLSFMEFEITFRPDSGDGVLLYSYDTGSKDFLSINLAGGHVEFRFDCGSGTGVLRSED
PLTLGNWHELRVSRTAKNGILQVDKQKIVEGMAEGGFTQIKCNTDIFIGGVPNYDDVKKNSGVLKPFS
GSIQKIILNDRTIHLE
NOV11c, CG94562-02	SEQ ID NO: 163	660 bp
DNA Sequence	ORF Start: at 7	ORF Stop: end of sequence
GGATCCGCACTCAGTGGGGCTGATGTGGGGGAATGCAGCAGTGGAATCTGTGATGAGGCCTCGTGCAT
CCATGGTGGCACCTGCACAGCAATCAAAGCCGACTCCTACATTTGCCTCTGTCCCCTTGGGTTTAAAG
GTCGACACTGTGAAGATGCTTTCACCTTGACCATTCCTCAGTTCAGAGAGTCTCTGAGATCTTACGCT
GCAACTCCCTGGCCACTGGAGCCCCAGCATTACCTTTCCTTCATGGAATTTGAGATCACATTTCGGCC
AGACTCAGGAGATGCTGTCCTCCTGTACAGCTATGACACAGGCAGCAAAGACTTCCTGTCCATCAACT
TGGCAGGGGGCCACGTGGAGTTCCGCTTTGACTGTGGCTCTGGGACCGGTGTCCTCAGCAGTGAAGAT
CCCCTCACCCTGGGCAACTGGCACGAGCTTCGTGTATCTCGCACAGCAAAGAATGGAATCTTACAGGT
GGATAAGCAGAAGATAGTGGAGGGAATCGCAGAGGGAGGCTTCACACAGATTAAGTGCAACACAGACA
TTTTCATTGGCGGAGTCCCCAATTATGATGATGTGAAGAAGAACTCGGGTGTCCTGAAGCCTTTCAGC
GGGAGCATCCAGAAGATCATCCTGAATGACCGAACCATCCATCTCGAG
NOV11c, CG94562-02
Protein Sequence	SEQ ID NO: 164	216 aa	MW at 23553.3kD
ALSGADVGECSSGICDEASCIHGGTCTAIKADSYICLCPLGFKGRHCEDAFTLTIPQFRESLRSYAAT
PWPLEPQHYLSFMEFEITFRPDSGDGVLLYSYDTGSKDFLSINLAGGHVEFRFDCGSGTGVLRSEDPL
TLGNWHELRVSRTAKNGILQVDKQKIVEGMAEGGFTQIKCNTDIFIGGVPNYDDVKKNSGVLKPFSGS
IQKIILNDRTIH

[0438] A ClustalW comparison of the above protein sequences yields the following sequence alignment shown in Table 11B.

TABLE 11B
Comparison of the NOV11 protein sequences.
NOV11a MPGQPSTCSPHSGYPKARHRSHLPAGPVPPPQNSNGASCQVSGSMWKEGKGKRGHRIAMG
NOV11b ------------------------------------------------------------
NOV11c ------------------------------------------------------------
NOV11a EGGCCSGSELCSENGKTSECQNSETEVQEQKVSSLGSGRMEEGNDQKDPGEVLGSSALLP
NOV11b ------------------------------------------------------------
NOV11c ------------------------------------------------------------
NOV11a RSCHCTPAWETERDSVSLKKKNVVTKQDRTKIPKSKGRRKFPTVTGEKASPVLVGLAGGT
NOV11b ------------------------------------------------------------
NOV11c ------------------------------------------------------------
NOV11a DRSSGICDEASCIHGGTCTAIKADSYICLCPLGFKGRHCEDIPQFRESLRSYAATPWPLE
NOV11b ------------------------------------------------------------
NOV11c ------------------------------------------------------------
NOV11a PQHYLSFMEFEITFRPDSGDGVLLYSYDTGSKDFLSINLAGGHVEFRFDCGSGTGVLRSE
NOV11b ------------------------------------------------------------
NOV11c ------------------------------------------------------------
NOV11a TKIKLGGWHTVMLYRDGLNGLLQLNNGTPVTGQSQGQYSKITFRTPLYLGGAPSAYWLVR
NOV11b ------------------------------------------------------------
NOV11c ------------------------------------------------------------
NOV11a ATGTNRGFQGCVQSLAVNGRRIDMRPWPLGKALSGADVGECSSGICDEASCIHGGTCTAI
NOV11b -----------------------------GSALSGADVGECSSGICDEASCIHGGTCTAI
NOV11c -------------------------------ALSGADVGECSSGICDEASCIHGGTCTAI
NOV11a KADSYICLCPLGFKGRHCEDAFTLTIPQFRESLRSYAATPWPLEPQHYLSFMEFEITFRP
NOV11b KADSYICLCPLGFKGRHCEDAFTLTIPQFRESLRSYAATPWPLEPQHYLSFMEFEITFRP
NOV11c KADSYICLCPLGFKGRHCEDAFTLTIPQFRESLRSYAATPWPLEPQHYLSFMEFEITFRP
NOV11a DSGDGVLLYSYDTGSKDFLSINLAGGHVEFRFDCGSGTGVLRSEDPLTLGNWHELRVSRT
NOV11b DSGDGVLLYSYDTGSKDFLSINLAGGHVEFRFDCGSGTGVLRSEDPLTLGNWHELRVSRT
NOV11c DSGDGVLLYSYDTGSKDFLSINLAGGHVEFRFDCGSGTGVLRSEDPLTLGNWHELRVSRT
NOV11a AKNGILQVDKQKIVEGVAEGGFTQIKCNTDIFIGGVPNYDDVKKNSGVLKPFSGSIQKII
NOV11b AKNGILQVDKQKIVEGMAEGGFTQIKCNTDIFIGGVPNYDDVKKNSGVLKPFSGSIQKII
NOV11c AKNGILQVDKQKIVEGMAEGGFTQIKCNTDIFIGGVPNYDDVKKNSGVLKPFSGSIQKII
NOV11a LNDRTIHVKHDFTSGVNVENAAHPCVRAPCAHGGSCRPRKEGYDCDCPLGFEGLHCQKGT
NOV11b LNDRTIHLE---------------------------------------------------
NOV11c LNDRTIH-----------------------------------------------------
NOV11a LRGLRHSSLEGVEGTDSQLGDHNKYLIVPRKENRNRSSAVGGMVQLPPKLPAESIHHPFY
NOV11b ------------------------------------------------------------
NOV11c ------------------------------------------------------------
NOV11a SSRETAPTSSHAQPWRAPSKHRSHSLPHCAWIYWCSRAPLHYHTFTNNQDTNILSSTVSE
NOV11b ------------------------------------------------------------
NOV11c ------------------------------------------------------------
NOV11a TYSSTELRQTPSGSNQISTINKMLPHSSPSEGNHSSWSFMIIYTRELFQGEYQHVRGSGR
NOV11b ------------------------------------------------------------
NOV11c ------------------------------------------------------------
NOV11a FFGGSESRVSGSRSNVFMRFKTTAKDGLLLWRGDSPMRPNSDFISLGLRDGALVFRYNLG
NOV11b ------------------------------------------------------------
NOV11c ------------------------------------------------------------
NOV11a SGVASIMVNGSFNDGRWHRVKAVRRDGQSGKITVDDYGARTGKSPGMMRQLNINGALYVG
NOV11b ------------------------------------------------------------
NOV11c ------------------------------------------------------------
NOV11a KE
NOV11b --
NOV11c --
NOV11a (SEQ ID NO: 160)
NOV11b (SEQ ID NO: 162)
NOV11c (SEQ ID NO: 164)

[0439] Further analysis of the NOV11 a protein yielded the following properties shown in Table 11C.

TABLE 11C
Protein Sequence Properties NOV11a
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 15; peak value 1.94
	PSG score: −2.46
	GvH: von Heijne's method for signal seq. recognition
	GvH score (threshold: −2.1): −11.01
	possible cleavage site: between 39 and 40
	>>> 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: 0
	number of TMS(s) . . . fixed
	PERIPHERAL Likelihood = 2.97 (at 892)
	ALOM score: 2.97 (number of TMSs: 0)
	MITDISC: discrimination of mitochondrial targeting seq
	R content:	2	Hyd Moment (75):	3.43
	Hyd Moment (95):	1.11	G content:	5
	D/E content:	1	S/T content:	9
	Score:	−3.79
	Gavel: prediction of cleavage sites for mitochondrial preseq
	R-2 motif at 66 HRI|AM
	NUCDISC: discrimination of nuclear localization signals
	pat4: RPRK (4) at 637
	pat7: PKSKGRR (3) at 153
	bipartite: none
	content of basic residues: 11.4%
	NLS Score: 0.04
	KDEL: ER retention motif in the C-terminus: none
	ER Membrane Retention Signals:
	KKXX-like motif in the C-terminus: YVGK
	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: 76.7
	COIL: Lupas's algorithm to detect coiled-coil regions
	total: 0 residues
	Final Results (k = 9/23):
	82.6%: nuclear
	8.7%: cytoplasmic
	4.3%: mitochondrial
	4.3%: peroxisomal
	>> prediction for CG94562-01 is nuc (k = 23)

[0440] A search of the NOV11 a protein against the Geneseq database, a proprietary database that contains sequences published in patents and patent publication, yielded several homologous proteins shown in Table 11D.

TABLE 11D
Geneseq Results for NOV11a
		NOV11a	Identities/
		Residues/	Similarities
Geneseq	Protein/Organism/Length	Match	for the	Expect
Identifier	[Patent #, Date]	Residues	Matched Region	Value
ABB72291	Rat protein isolated from skin cells	187 . . . 658	380/482 (78%)	0.0
	SEQ ID NO: 503 - Rattus sp, 819	157 . . . 631	409/482 (84%)
	aa. [WO200190357-A1, 29 NOV.
	2001]
ABJ05729	Novel human protein SEQ ID No	415 . . . 664	243/250 (97%)	e−148
	78 - Homo sapiens, 432 aa.	1 . . . 250	246/250 (98%)
	[US2002086330-A1, 04 JUL. 2002]
ABP66820	Human polypeptide SEQ ID NO	415 . . . 664	243/250 (97%)	e−148
	541 - Homo sapiens, 432 aa.	1 . . . 250	246/250 (98%)
	[US2002090672-A1, 11 JUL. 2002]
AAU19905	Novel human calcium-binding	415 . . . 664	243/250 (97%)	e−148
	protein #14 - Homo sapiens, 432 aa.	1 . . . 250	246/250 (98%)
	[WO200155304-A2, 02 AUG.
	2001]
AAU16938	Human novel secreted protein, SEQ	415 . . . 664	243/250 (97%)	e−148
	ID 179 - Homo sapiens, 432 aa.	1 . . . 250	246/250 (98%)
	[WO200155441-A2, 02 AUG.
	2001]

[0441] In a BLAST search of public sequence databases, the NOV11a protein was found to have 5 homology to the proteins shown in the BLASTP data in Table 11E.

TABLE 11E
Public BLASTP Results for NOV11a
		NOV11a	Identities/
Protein		Residues/	Similarities
Accession		Match	for the	Expect
Number	Protein/Organism/Length	Residues	Matched Portion	Value
Q8N7Y0	Hypothetical protein FLJ40230 -	187 . . . 664	396/489 (80%)	0.0
	Homo sapiens (Human), 775 aa.	113 . . . 593	420/489 (84%)
Q8BGP3	Hypothetical EGF-like domain -	187 . . . 664	381/488 (78%)	0.0
	Mus musculus (Mouse), 1009 aa.	347 . . . 827	412/488 (84%)
Q8BU56	Hypothetical EGF-like domain -	187 . . . 599	324/423 (76%)	0.0
	Mus musculus (Mouse), 822 aa.	347 . . . 762	352/423 (82%)
Q8NAL2	Hypothetical protein FLJ35160 -	384 . . . 664	274/281 (97%)	e−168
	Homo sapiens (Human), 463 aa.	1 . . . 281	277/281 (98%)
Q9NGV2	SP2353 - Drosophila	33 . . . 740	251/849 (29%)	4e−89
	melanogaster (Fruit fly), 1361 aa.	76 . . . 901	373/849 (43%)

[0442] PFam analysis predicts that the NOV11a protein contains the domains shown in the Table 11F.

TABLE 11F
Domain Analysis of NOV11a
Pfam	NOV11a Match	Identities/Similarities	Expect
Domain	Region	for the Matched Region	Value
EGF	187 . . . 219	13/47	(28%)	9.3e−07
		22/47	(47%)
laminin_G	254 . . . 383	46/155	(30%)	1.1e−26
		96/155	(62%)
EGF	406 . . . 438	13/47	(28%)	9.3e−07
		22/47	(47%)
laminin_G	478 . . . 607	41/155	(26%)	4e−25
		99/155	(64%)
EGF	625 . . . 656	14/47	(30%)	3.4e−05
		21/47	(45%)
laminin_G	860 . . . 959	36/155	(23%)	0.00015
		82/155	(53%)

Example B

Sequencing Methodology and Identification of NOVX Clones

[0443] 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.

[0444] 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.

[0445] 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.

[0446] The laboratory screening was performed using the methods summarized below:

[0447] 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).

[0448] 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.

[0449] 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).

[0450] 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.

[0451] 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.I 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.

[0452] 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.

[0453] The PCR product derived by exon linking, covering the entire open reading frame, was cloned into the pCR2. 1 vector from Invitrogen to provide clones used for expression and screening purposes.

Example C

Quantitative Expression Analysis of Clones in Various Cells and Tissues

[0454] 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 PRISMS® 7700 or an ABI PRISMS® 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), AI13comprehensive13panel (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).

[0455] 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.

[0456] 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.

[0457] 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 1X TaqMang® Universal Master mix (Applied Biosystems; catalog No. 4324020), following the manufacturer's instructions.

[0458] 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 75bp to 100bp. 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, 900nM each, and probe, 200nM.

[0459] 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. Expression with CT values below 28 is considered as high expression, CT values between 28 and 32 is considered moderate and CT value between 32 to 35 is considered as low expression. All the relative expression with CT values above 35 is not considered as significant expression.

[0460] 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.

[0461] Panels 1, 1.1, 1.2, and 1.3D

[0462] 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.

[0463] In the results for Panels 1, 1.1, 1.2 and 1.3D, the following abbreviations are used:

[0464] ca.=carcinoma,

[0465] *=established from metastasis,

[0466] met=metastasis,

[0467] s cell var=small cell variant,

[0468] non-s=non-sm =non-small,

[0469] squam=squamous,

[0470] pl. eff=pl effusion=pleural effusion,

[0471] glio=glioma,

[0472] astro=astrocytoma, and

[0473] neuro=neuroblastoma.

[0474] General_screening_panel_v1.4, v1.5, v1.6 and 1.7

[0475] 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.

[0476] Panels 2D, 2.2, 2.3 and 2.4

[0477] 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.

[0478] HASS Panel v 1.0

[0479] 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.

[0480] ARDAIS Panel v 1.0

[0481] 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.

[0482] ARDAIS Prostate v 1.0

[0483] The plates for ARDAIS prostate 1.0 generally include 2 control wells and 68 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 prostate malignancies and in cases where indicated malignant samples have “matched margins” obtained from noncancerous prostate 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). RNA from unmatched malignant and non-malignant prostate samples 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.

[0484] Panel 3D, 3.1 and 3.2

[0485] 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.

[0486] Panels 4D, 4R, and 4.1D

[0487] 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.).

[0488] 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-1 3 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.

[0489] 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.

[0490] 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), 1mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), and 10mM Hepes (Gibco), 50 ng/ml GMCSF and 5ng/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.

[0491] 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.

[0492] To obtain B cells, tonsils were procured from NDRI. The tonsil was cut up with sterile dissecting scissors and then passed through a sieve. Tonsil cells were then spun down and resupended at 106 cells/ml in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), and 10 mM Hepes (Gibco). To activate the cells, we used PWM at 5 μg/ml or anti-CD40 (Pharmingen) at approximately 10 μg/ml and IL-4 at 5-10 ng/ml. Cells were harvested for RNA preparation at 24,48 and 72 hours.

[0493] To prepare the primary and secondary Th1/Th2 and Tr1 cells, six-well Falcon plates were coated overnight with 10 μg/ml anti-CD28 (Pharmingen) and 2 μg/ml OKT3 (ATCC), and then washed twice with PBS. Umbilical cord blood CD4 lymphocytes (Poietic Systems, German Town, Md.) were cultured at 105-106 cells/ml in DMEM 5% FCS (Hyclone), 10 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 82 g/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.

[0494] The following leukocyte cells lines were obtained from the ATCC: Ramos, EOL-1, KU-812. EOL cells were further differentiated by culture in 0.1 mM dbcAMP at 5×105 cells/ml for 8 days, changing the media every 3 days and adjusting the cell concentration to 5×105 cells/ml. For the culture of these cells, we used DMEM or RPMI (as recommended by the ATCC), with the addition of 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5M (Gibco), 10 mM Hepes (Gibco). RNA was either prepared from resting cells or cells activated with PMA at 10 ng/ml and ionomycin at 1 μg/ml for 6 and 14 hours. Keratinocyte line CCD106 and an airway epithelial tumor line NCI-H292 were also obtained from the ATCC. Both were cultured in DMEM 5% FCS (Hyclone), 100 μM non essential amino acids (Gibco), 1 mM sodium pyruvate (Gibco), mercaptoethanol 5.5×10−5 M (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 IL4, 5 ng/ml IL-9, 5 ng/ml IL-13 and 25 ng/ml IFN gamma.

[0495] 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.

[0496] AI_comprehensive panel_v1.0

[0497] 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.

[0498] 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.

[0499] 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.

[0500] 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.

[0501] Total RNA from post mortem lung tissue from trauma victims with no disease or with emphysema, asthma or COPD was purchased from Clinomics. Emphysema patients ranged in age from 40-70 and all were smokers, this age range was chosen to focus on patients with cigarette-linked emphysema and to avoid those patients with alpha-1anti-trypsin deficiencies. Asthma patients ranged in age from 36-75, and excluded smokers to prevent those patients that could also have COPD. COPD patients ranged in age from 35-80 and included both smokers and non-smokers. Most patients were taking corticosteroids, and bronchodilators.

[0502] In the labels employed to identify tissues in the AI_comprehensive panel_v1.0 panel, the following abbreviations are used:

[0503] AI=Autoimmunity

[0504] Syn=Synovial

[0505] Normal=No apparent disease

[0506] Rep22/Rep20=individual patients

[0507] RA=Rheumatoid arthritis

[0508] Backus=From Backus Hospital

[0509] OA=Osteoarthritis

[0510] (SS) (BA) (MF)=Individual patients

[0511] Adj=Adjacent tissue

[0512] Match control=adjacent tissues

[0513] −M=Male

[0514] −F=Female

[0515] COPD=Chronic obstructive pulmonary disease

[0516] AI.05 Chondrosarcoma

[0517] The AI.05 chondrosarcoma plates are comprised of SW1353 cells that had been subjected to serum starvation and treatment with cytokines that are known to induce MMP (1, 3 and 13) synthesis (eg. IL1beta). These treatments include: IL-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.

[0518] Panels 5D and 5I

[0519] 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.

[0520] In the Gestational Diabetes study subjects are young (18-40 years), otherwise healthy women with and without gestational diabetes undergoing routine (elective) Caesarean section. After delivery of the infant, when the surgical incisions were being repaired/closed, the obstetrician removed a small sample (less than 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:

[0521] Patient 2: Diabetic Hispanic, overweight, not on insulin

[0522] Patient 7-9: Nondiabetic Caucasian and obese (BMI>30)

[0523] Patient 10: Diabetic Hispanic, overweight, on insulin

[0524] Patient 11: Nondiabetic African American and overweight

[0525] Patient 12: Diabetic Hispanic on insulin

[0526] Adiocyte differentiation was induced in donor progenitor cells obtained from Osirus (a division of Clonetics/BioWhittaker) in triplicate, except for Donor 3 U 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:

[0527] Donor 2 and 3 U: Mesenchymal Stem cells, Undifferentiated Adipose

[0528] Donor 2 and 3 AM: Adipose, AdiposeMidway Differentiated

[0529] Donor 2 and 3 AD: Adipose, Adipose Differentiated

[0530] 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.

[0531] 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.

[0532] In the labels employed to identify tissues in the 5D and 5I panels, the following abbreviations are used:

[0533] GO Adipose=Greater Omentum Adipose

[0534] SK=Skeletal Muscle

[0535] UT=Uterus

[0536] PL=Placenta

[0537] AD=Adipose Differentiated

[0538] AM=Adipose Midway Differentiated

[0539] U=Undifferentiated Stem Cells

[0540] Human Metabolic RTQ-PCR Panel

[0541] The plates for the Human Metabolic RTQ-PCR Panel include two control wells (genomic DNA control and chemistry control) and 211 cDNAs isolated from human tissues and cell lines with an emphasis on metabolic diseases. This panel is useful for establishing the tissue and cellular expression profiles for genes believed to play a role in the etiology and pathogenesis of obesity and/or diabetes and to confirm differential expression of such genes derived from other methods. Metabolic tissues were obtained from patients enrolled in the CuraGen Gestational Diabetes study and from autopsy tissues from Type II diabetics and age, sex and race-matched control patients. One or more of the following were used to characterize the patients: body mass index [BMI=wt (kg)/ht (m2)], serum glucose, HgbA1c. Cell lines used in this panel are widely available through the American Type Culture Collection (ATCC), a repository for cultured cell lines. RNA from human Pancreatic Islets was also obtained.

[0542] In the Gestational Diabetes study, subjects are young (18-40 years), otherwise healthy women with and without gestational diabetes undergoing routine (elective) Caesarian section. After delivery of the infant, when the surgical incisions were being repaired/closed, the obstetrician removed a small sample (less than 1 cc) of the exposed metabolic tissues during the closure of each surgical level. The biopsy material was rinsed in sterile saline, blotted, and 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:

[0543] Patient 7—Non-diabetic Caucasian and obese

[0544] Patient 8—Non-diabetic Caucasian and obese

[0545] Patient 12—Diabetic Caucasian with unknown BMI and on insulin

[0546] Patient 13—Diabetic Caucasian, overweight, not on insulin

[0547] Patient 15—Diabetic Caucasian, obese, not on insulin

[0548] Patient 17—Diabetic Caucasian, normal weight, not on insulin

[0549] Patient 18—Diabetic Hispanic, obese, not on insulin

[0550] Patient 19—Non-diabetic Caucasian and normal weight

[0551] Patient 20—Diabetic Caucasian, overweight, and on insulin

[0552] Patient 21—Non-diabetic Caucasian and overweight

[0553] Patient 22—Diabetic Caucasian, normal weight, on insulin

[0554] Patient 23—Non-diabetic Caucasian and overweight

[0555] Patient 25—Diabetic Caucasian, normal weight, not on insulin

[0556] Patient 26—Diabetic Caucasian, obese, on insulin

[0557] Patient 27—Diabetic Caucasian, obese, on insulin

[0558] Total RNA was isolated from metabolic tissues of 12 Type II diabetic patients and 12 matched control patients included hypothalamus, liver, pancreas, small intestine, psoas muscle, diaphragm muscle, visceral adipose, and subcutaneous adipose. The diabetics and non-diabetics were matched for age, sex, ethnicity, and BMI where possible.

[0559] The panel also contains pancreatic islets from a 22 year old male patient (with a BMI of 35) obtained from the Diabetes Research Institute at the University of Miami School of Medicine. Islet tissue was processed to total RNA at CuraGen.

[0560] Cell lines used in this panel are widely available through the American Type Culture Collection (ATCC), a repository for cultured cell lines, and were cultured at an outside facility. The RNA was extracted at CuraGen according to CuraGen protocols. All samples were then processed at CuraGen to produce single stranded cDNA.

[0561] In the labels used to identify tissues in the Human Metabolic panel, the following abbreviations are used:

[0562] Pl=placenta

[0563] Go=greater omentum

[0564] Sk=skeletal muscle

[0565] Ut=uterus

[0566] CC=Caucasian

[0567] HI=Hispanic

[0568] AA=African American

[0569] AS=Asian

[0570] Diab=Type II diabetic

[0571] Norm=Non-diabetic

[0572] Overwt=Overweight; med BMI

[0573] Obese=Hi BMI

[0574] Low BM=20-25

[0575] Med BM=26-30

[0576] Hi BMI=Greater than 30

[0577] M=Male

[0578] #=Patient identifier

[0579] Vis.=Visceral

[0580] SubQ=Subcutaneous

[0581] Panel CNSD.01

[0582] 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.

[0583] 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.

[0584] In the labels employed to identify tissues in the CNS panel, the following abbreviations are used:

[0585] PSP=Progressive supranuclear palsy

[0586] Sub Nigra=Substantia nigra

[0587] Glob Palladus=Globus palladus

[0588] Temp Pole=Temporal pole

[0589] Cing Gyr=Cingulate gyrus

[0590] BA 4=Brodman Area 4

[0591] Panel CNS13 Neurodegeneration_V1.0

[0592] 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.

[0593] 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.

[0594] In the labels employed to identify tissues in the CNS_Neurodegencration_V1.0 panel, the following abbreviations are used:

[0595] AD=Alzheimer's disease brain; patient was demented and showed AD-like pathology upon autopsy

[0596] Control=Control brains; patient not demented, showing no neuropathology

[0597] Control (Path)=Control brains; pateint not demented but showing sever AD-like pathology

[0598] SupTemporal Ctx=Superior Temporal Cortex

[0599] Inf Temporal Ctx=Inferior Temporal Cortex

[0600] Panel CNS_Neurodegeneration_V2.0

[0601] The plates for Panel CNS_Neurodegeneration_V2.0 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.

[0602] Disease diagnoses are taken from patient records. The panel contains sixteen brains from Alzheimer's disease (AD) patients, and twenty-nine brains from “Normal controls” who showed no evidence of dementia prior to death. The twenty-nine normal control brains are divided into two categories: Fourteen controls with no dementia and no Alzheimer's like pathology (Controls) and fifteen 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). Tissue from the temporal cotex (Broddmann Area 21) was selected for all samples from the Harvard Brain Tissue Resource Center; from the two sample from the Human Brain and Spinal Fluid Resource Center (samples 1 and 2) tissue from the inferior and superior temporal cortex was used; each sample on the panel represents a pool of inferior and superior temporal cortex from an individual patient. The temporal cortex was chosen as it shows a loss of neurons in the intermediate stages of the disease. Selection of a region which is affected in the early stages of Alzheimer's disease (e.g., hippocampus or entorhinal cortex) could potentially result in the examination of gene expression after vulnerable neurons are lost, and missing genes involved in the actual neurodegeneration process.

[0603] In the labels employed to identify tissues in the CNS_Neurodegeneration_V2.0 panel, the following abbreviations are used:

[0604] AD=Alzheimer's disease brain; patient was demented and showed AD-like pathology upon autopsy

[0605] Control=Control brains; patient not demented, showing no neuropathology

[0606] AH3=Control brains; pateint not demented but showing sever AD-like pathology

[0607] Inf & Sup Temp Ctx Pool=Pool of inferior and superior temporal cortex for a given individual

A. NOV1, CG108537-01: Sugar Transporter

[0608] Expression of gene CG108537-01 was assessed using the primer-probe sets Ag4365 and Ag5488, described in Tables AA and AB. Results of the RTQ-PCR runs are shown in Tables AC, AD, AE and AF.

TABLE AA
Probe Name Ag4365
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ccctgctctctgacctcttc-3′	20	454	165
Probe	TET-5′-cactgtcgccaggcctactctgtcta-3′-	26	486	166
	TAMRA
Reverse	5′-ccccaagactgatcatgaag-3	20	515	167

[0609]

TABLE AB
Probe Name Ag5488
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-cggagacactatgatgaaggtgtt-3′	24	960	168
Probe	TET-5′-ctgttcctgcagtgcgccatctc-3′-	23	1002	169
	TAMRA
Reverse	5′-gtccatgaccagagagaagacc-3′	22	1028	170

[0610]

TABLE AC
CNS_neurodegeneration_v1.0
	Tissue Name	A	B
	AD 1 Hippo	35.1	34.9
	AD 2 Hippo	48.0	52.1
	AD 3 Hippo	6.4	8.4
	AD 4 Hippo	18.0	13.7
	AD 5 hippo	40.9	44.8
	AD 6 Hippo	36.9	33.4
	Control 2 Hippo	30.6	20.6
	Control 4 Hippo	21.9	8.4
	Control (Path) 3 Hippo	4.5	3.8
	AD 1 Temporal Ctx	31.4	17.9
	AD 2 Temporal Ctx	29.5	28.5
	AD 3 Temporal Ctx	10.3	5.8
	AD 4 Temporal Ctx	20.9	18.8
	AD 5 Inf Temporal Ctx	100.0	100.0
	AD 5 SupTemporal Ctx	47.3	63.3
	AD 6 Inf Temporal Ctx	62.0	72.2
	AD 6 Sup Temporal Ctx	33.2	40.3
	Control 1 Temporal Ctx	2.3	6.2
	Control 2 Temporal Ctx	27.2	33.7
	Control 3 Temporal Ctx	4.5	3.8
	Control 4 Temporal Ctx	4.7	11.3
	Control (Path) 1 Temporal Ctx	10.1	18.6
	Control (Path) 2 Temporal Ctx	8.0	9.0
	Control (Path) 3 Temporal Ctx	1.5	2.0
	Control (Path) 4 Temporal Ctx	6.0	9.3
	AD 1 Occipital Ctx	14.9	15.7
	AD 2 Occipital Ctx (Missing)	0.0	0.0
	AD 3 Occipital Ctx	11.6	6.9
	AD 4 Occipital Ctx	12.0	30.1
	AD 5 Occipital Ctx	16.5	25.3
	AD 6 Occipital Ctx	14.2	13.5
	Control 1 Occipital Ctx	6.2	5.6
	Control 2 Occipital Ctx	29.5	37.6
	Control 3 Occipital Ctx	8.8	4.1
	Control 4 Occipital Ctx	21.0	14.8
	Control (Path) 1 Occipital Ctx	56.3	79.0
	Control (Path) 2 Occipital Ctx	11.3	14.3
	Control (Path) 3 Occipital Ctx	1.5	1.2
	Control (Path) 4 Occipital Ctx	7.9	8.2
	Control 1 Parietal Ctx	11.0	17.4
	Control 2 Parietal Ctx	48.0	52.5
	Control 3 Parietal Ctx	16.3	29.7
	Control (Path) 1 Parietal Ctx	20.9	27.2
	Control (Path) 2 Parietal Ctx	21.6	26.2
	Control (Path) 3 Parietal Ctx	1.2	4.6
	Control (Path) 4 Parietal Ctx	21.9	21.8
	Column A - Rel. Exp. (%) Ag4365, Run 224374594
	Column B - Rel. Exp. (%) Ag4365, Run 229929874

[0611]

TABLE AD
General_screening_panel_v1.4
Tissue Name                      A
Adipose                          0.3
Melanoma* Hs688(A).T             0.4
Melanoma* Hs688(B).T             0.8
Melanoma* M14                    2.5
Melanoma* LOXIMVI                2.4
Melanoma* SK-MEL-5               2.4
Squamous cell carcinoma SCC-4    1.3
Testis Pool                      0.4
Prostate ca.* (bone met) PC-3    3.1
Prostate Pool                    100.0
Placenta                         0.0
Uterus Pool                      0.1
Ovarian ca. OVCAR-3              2.6
Ovarian ca. SK-OV-3              4.0
Ovarian ca. OVCAR-4              1.0
Ovarian ca. OVCAR-5              11.0
Ovarian ca. IGROV-1              1.8
Ovarian ca. OVCAR-8              2.8
Ovary                            1.8
Breast ca. MCF-7                 0.6
Breast ca. MDA-MB-231            4.0
Breast ca. BT 549                2.7
Breast ca. T47D                  35.4
Breast ca. MDA-N                 1.8
Breast Pool                      0.9
Trachea                          2.7
Lung                             0.4
Fetal Lung                       1.1
Lung ca. NCI-N417                0.5
Lung ca. LX-1                    17.2
Lung ca. NCI-H146                1.2
Lung ca. SHP-77                  0.0
Lung ca. A549                    1.2
Lung ca. NCI-H526                0.7
Lung ca. NCI-H23                 1.7
Lung ca. NCI-H460                0.5
Lung ca. HOP-62                  1.8
Lung ca. NCI-H522                3.8
Liver                            0.5
Fetal Liver                      2.3
Liver ca. HepG2                  1.4
Kidney Pool                      1.6
Fetal Kidney                     1.5
Renal ca. 786-0                  1.5
Renal ca. A498                   0.9
Renal ca. ACHN                   1.5
Renal ca. UO-31                  2.6
Renal ca. TK-10                  4.5
Bladder                          1.3
Gastric ca. (liver met.) NCI-N87 5.3
Gastric ca. KATO III             9.1
Colon ca. SW-948                 5.6
Colon ca. SW480                  3.3
Colon ca.* (SW480 met) SW620     2.4
Colon ca. HT29                   8.8
Colon ca. HCT-116                4.5
Colon ca. CaCo-2                 4.1
Colon cancer tissue              1.8
Colon ca. SW1116                 1.1
Colon ca. Colo-205               16.3
Colon ca. SW-48                  3.0
Colon Pool                       1.2
Small Intestine Pool             0.7
Stomach Pool                     0.4
Bone Marrow Pool                 0.5
Fetal Heart                      0.2
Heart Pool                       0.5
Lymph Node Pool                  0.8
Fetal Skeletal Muscle            0.2
Skeletal Muscle Pool             0.3
Spleen Pool                      2.7
Thymus Pool                      0.8
CNS cancer (glio/astro) U87-MG   1.3
CNS cancer (glio/astro) U-118-MG 0.4
CNS cancer (neuro; met) SK-N-AS  7.4
CNS cancer (astro) SF-539        0.5
CNS cancer (astro) SNB-75        2.3
CNS cancer (glio) SNB-19         1.7
CNS cancer (glio) SF-295         1.7
Brain (Amygdala) Pool            5.1
Brain (cerebellum)               1.3
Brain (fetal)                    4.3
Brain (Hippocampus) Pool         3.2
Cerebral Cortex Pool             2.0
Brain (Substantia nigra) Pool    7.0
Brain (Thalamus) Pool            4.6
Brain (whole)                    1.5
Spinal Cord Pool                 10.5
Adrenal Gland                    0.7
Pituitary gland Pool             1.0
Salivary Gland                   0.4
Thyroid (female)                 0.5
Pancreatic ca. CAPAN2            4.3
Pancreas Pool                    1.4
Column A - Rel. Exp. (%) Ag4365, Run 222543453

[0612]

TABLE AE
General_screening_panel_v1.5
Tissue Name                      A
Adipose                          0.2
Melanoma* Hs688(A).T             0.6
Melanoma* Hs688(B).T             0.6
Melanoma* M14                    3.6
Melanoma* LOXIMVI                3.0
Melanoma* SK-MEL-5               4.8
Squamous cell carcinoma SCC-4    1.3
Testis Pool                      0.7
Prostate ca.* (bone met) PC-3    1.3
Prostate Pool                    100.0
Placenta                         0.2
Uterus Pool                      0.3
Ovarian ca. OVCAR-3              3.5
Ovarian ca. SK-OV-3              5.2
Ovarian ca. OVCAR-4              1.3
Ovarian ca. OVCAR-5              15.9
Ovarian ca. IGROV-1              2.0
Ovarian ca. OVCAR-8              2.5
Ovary                            0.9
Breast ca. MCF-7                 1.2
Breast ca. MDA-MB-231            4.3
Breast ca. BT 549                2.4
Breast ca. T47D                  0.7
Breast ca. MDA-N                 1.6
Breast Pool                      0.6
Trachea                          2.1
Lung                             0.1
Fetal Lung                       1.3
Lung ca. NCI-N417                0.6
Lung ca. LX-1                    22.1
Lung ca. NCI-H146                1.1
Lung ca. SHP-77                  0.0
Lung ca. A549                    1.4
Lung ca. NCI-H526                1.0
Lung ca. NCI-H23                 3.4
Lung ca. NCI-H460                1.0
Lung ca. HOP-62                  1.5
Lung ca. NCI-H522                4.3
Liver                            0.8
Fetal Liver                      4.3
Liver ca. HepG2                  3.7
Kidney Pool                      0.7
Fetal Kidney                     0.5
Renal ca. 786-0                  1.8
Renal ca. A498                   1.5
Renal ca. ACHN                   1.6
Renal ca. UO-31                  4.2
Renal ca. TK-10                  3.6
Bladder                          1.0
Gastric ca. (liver met.) NCI-N87 6.9
Gastric ca. KATO III             18.3
Colon ca. SW-948                 4.5
Colon ca. SW480                  4.1
Colon ca.* (SW480 met) SW620     3.5
Colon ca. HT29                   14.2
Colon ca. HCT-116                5.4
Colon ca. CaCo-2                 5.9
Colon cancer tissue              1.2
Colon ca. SW1116                 1.3
Colon ca. Colo-205               17.1
Colon ca. SW-48                  4.1
Colon Pool                       0.6
Small Intestine Pool             0.6
Stomach Pool                     0.5
Bone Marrow Pool                 0.3
Fetal Heart                      0.2
Heart Pool                       0.3
Lymph Node Pool                  1.3
Fetal Skeletal Muscle            0.1
Skeletal Muscle Pool             1.2
Spleen Pool                      1.4
Thymus Pool                      0.5
CNS cancer (glio/astro) U87-MG   0.8
CNS cancer (glio/astro) U-118-MG 0.5
CNS cancer (neuro; met) SK-N-AS  5.1
CNS cancer (astro) SF-539        0.3
CNS cancer (astro) SNB-75        2.7
CNS cancer (glio) SNB-19         2.1
CNS cancer (glio) SF-295         1.6
Brain (Amygdala) Pool            3.9
Brain (cerebellum)               1.2
Brain (fetal)                    4.8
Brain (Hippocampus) Pool         2.4
Cerebral Cortex Pool             2.1
Brain (Substantia nigra) Pool    4.2
Brain (Thalamus) Pool            4.7
Brain (whole)                    2.0
Spinal Cord Pool                 10.3
Adrenal Gland                    1.0
Pituitary gland Pool             0.8
Salivary Gland                   0.4
Thyroid (female)                 0.3
Pancreatic ca. CAPAN2            6.7
Pancreas Pool                    1.4
Column A - Rel. Exp. (%) Ag5488, Run 244646952

[0613]

TABLE AF
Panel 4.1D
Tissue Name	A	B
Secondary Th1 act	3.0	0.0
Secondary Th2 act	0.0	0.0
Secondary Tr1 act	2.1	0.0
Secondary Th1 rest	0.0	0.0
Secondary Th2 rest	0.0	0.0
Secondary Tr1 rest	0.0	0.0
Primary Th1 act	2.6	0.0
Primary Th2 act	3.0	0.0
Primary Tr1 act	0.0	0.0
Primary Th1 rest	0.0	0.0
Primary Th2 rest	0.0	0.0
Primary Tr1 rest	0.0	0.0
CD45RA CD4 lymphocyte act	0.7	7.2
CD45RO CD4 lymphocyte act	0.7	3.2
CD8 lymphocyte act	0.0	0.0
Secondary CD8 lymphocyte rest	1.9	2.5
Secondary CD8 lymphocyte act	0.4	0.0
CD4 lymphocyte none	0.0	0.0
2ry Th1/Th2/Tr1_anti-CD95 CH11	1.0	0.0
LAK cells rest	16.7	10.2
LAK cells IL-2	1.7	4.6
LAK cells IL-2 + IL-12	2.2	0.0
LAK cells IL-2 + IFN gamma	0.0	0.0
LAK cells IL-2 + IL-18	2.3	0.0
LAK cells PMA/ionomycin	0.0	5.6
NK Cells IL-2 rest	2.6	3.0
Two Way MLR 3 day	9.8	5.1
Two Way MLR 5 day	5.3	0.0
Two Way MLR 7 day	0.7	2.2
PBMC rest	7.9	0.0
PBMC PWM	4.1	2.1
PBMC PHA-L	3.5	0.0
Ramos (B cell) none	7.6	1.3
Ramos (B cell) ionomycin	2.6	5.7
B lymphocytes PWM	8.1	6.3
B lymphocytes CD40L and IL-4	15.5	26.6
EOL-1 dbcAMP	11.0	12.3
EOL-1 dbcAMP PMA/ionomycin	6.4	0.0
Dendritic cells none	21.3	32.5
Dendritic cells LPS	5.5	3.5
Dendritic cells anti-CD40	21.2	14.4
Monocytes rest	1.2	0.0
Monocytes LPS	0.0	0.0
Macrophages rest	100.0	11.3
Macrophages LPS	10.3	6.7
HUVEC none	25.2	22.5
HUVEC starved	35.4	62.9
HUVEC IL-1beta	14.2	25.3
HUVEC IFN gamma	14.7	0.4
HUVEC TNF alpha + IFN gamma	4.4	3.0
HUVEC TNF alpha + IL4	27.0	10.2
HUVEC IL-11	12.3	44.1
Lung Micro vascular EC none	35.4	100.0
Lung Microvascular EC TNFalpha + IL-1beta	14.7	9.7
Microvascular Dermal EC none	26.1	2.3
Microsvasular Dermal EC TNFalpha + IL-1 beta	13.1	5.4
Bronchial epithelium TNFalpha + IL1beta	3.4	2.5
Small airway epithelium none	4.6	6.5
Small airway epithelium TNFalpha + IL-1beta	0.0	3.3
Coronery artery SMC rest	5.1	15.8
Coronery artery SMC TNFalpha + IL-1beta	8.8	17.2
Astrocytes rest	1.2	4.7
Astrocytes TNFalpha + IL-1beta	1.3	2.1
KU-812 (Basophil) rest	20.7	47.3
KU-812 (Basophil) PMA/ionomycin	27.9	48.0
CCD1106 (Keratinocytes) none	10.0	18.9
CCD1106 (Keratinocytes) TNFalpha + IL-1beta	5.1	5.1
Liver cirrhosis	17.2	11.3
NCI-H292 none	10.9	27.5
NCI-H292 IL-4	17.9	43.2
NCI-H292 IL-9	7.5	25.3
NCI-H292 IL-13	14.2	62.4
NCI-H292 IFN gamma	7.0	4.0
HPAEC none	18.6	23.8
HPAEC TNF alpha + IL-1 beta	9.2	25.5
Lung fibroblast none	6.5	5.3
Lung fibroblast TNF alpha + IL-1 beta	3.0	5.7
Lung fibroblast IL-4	7.0	12.6
Lung fibroblast IL-9	4.1	3.1
Lung fibroblast IL-13	18.0	2.8
Lung fibroblast IFN gamma	0.0	0.0
Dermal fibroblast CCD1070 rest	4.7	20.0
Dermal fibroblast CCD1070 TNF alpha	4.4	13.5
Dermal fibroblast CCD1070 IL-1 beta	8.5	0.0
Dermal fibroblast IFN gamma	0.0	0.0
Dermal fibroblast IL-4	3.7	7.0
Dermal Fibroblasts rest	0.0	0.0
Neutrophils TNFa + LPS	2.0	5.4
Neutrophils rest	0.6	0.0
Colon	14.1	5.5
Lung	3.8	1.4
Thymus	8.7	0.0
Kidney	72.7	15.3
Column A - Rel. Exp. (%) Ag4365, Run 186367307
Column B - Rel. Exp. (%) Ag5488, Run 244640003

[0614] CNS_neurodegeneration_v1.0 Summary: This gene is found to be upregulated in the temporal cortex of Alzheimer's disease patients. Blockade of this receptor is of use in the treatment of this disease and to decrease neuronal cell death.

[0615] General_screening_panel_v1.4 Summary: Ag4365 Highest expression of this gene is detected in prostate tissue (CT=25.8) in this panel. Therefore, therapeutic modulation of this gene or its protein product is useful in the treatment of prostate related diseases.

[0616] Moderate expression of this gene is seen in a 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 is useful as a marker to detect the presence of these cancers. Furthermore, therapeutic modulation of the expression or function of this gene or gene product will be effective in the treatment of pancreatic, gastric, colon, lung, liver, renal, breast, ovarian, prostate, squamous cell carcinoma, melanoma and brain cancers.

[0617] 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, liver and the gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene will prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0618] 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 will be useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0619] General_screening_panel_v1.5 Summary: Ag5488 Highest expression of this gene is detected in prostate (CT=26.8) in this panel. This gene shows wide spread expression in this panel which correlates with expression pattern in panel 1.4.

[0620] Panel 4.1D Summary: Ag4365/Ag5488 In this panel, the highest expression of this gene is seen in resting macrophage and lung microvascular endothelial cells (CTs=30-31). Significant expression of this gene is also seen in resting LAK cells, CD40L and IL-4 treated B cells, eosinophils, dendritic cells, HUVEC, resting and activated lung microvascular endothelial cells, HPAEC, Coronery artery SMC, basophils, keratinocytes, NCI-H292 cells, lung fibroblasts, dermal fibroblasts, and liver cirrhosis. Therefore, therapeutic modulation of this gene or its protein product will be useful in the treatment of autoimmune and inflammatory diseases such as asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, rheumatoid arthritis, osteoarthritis and liver cirrhosis.

B. NOV 2, CG51373-01: Nephrin Like

[0621] Expression of gene CG51373-01 was assessed using the primer-probe sets Ag271 and Ag271b, described in Tables BA and BB. Results of the RTQ-PCR runs are shown in Tables BC, BD.

TABLE BA
Probe Name Ag271
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-acctggacatagggcgtgtct-3′	21	824	171
Probe	TET-5′-cgaagcatgaacgaagccatccctag-3′-	26	853	172
	TAMRA
Reverse	5′-tcgatggaagtctccttgcc-3′	20	880	173

[0622]

TABLE BB
Probe Name Ag271b
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-caccgtgagccaactgcttat-3′	21	792	174
Probe	TET-5′-agacacgccctatgtccaggtccg-3′-	24	821	175
	TAMRA
Reverse	5′-ttcgttcatgcttcggcaa-3′	19	849	176

[0623]

TABLE BC
General_screening_panel_v1.4
	Tissue Name	A	B
	Adipose	6.4	6.4
	Melanoma* Hs688(A).T	29.7	28.1
	Melanoma* Hs688(B).T	26.4	25.7
	Melanoma* M14	49.0	48.0
	Melanoma* LOXIMVI	28.7	31.2
	Melanoma* SK-MEL-5	9.4	11.7
	Squamous cell carcinoma SCC-4	5.0	5.4
	Testis Pool	1.8	1.6
	Prostate ca.* (bone met) PC-3	19.8	22.4
	Prostate Pool	2.0	2.4
	Placenta	4.5	7.7
	Uterus Pool	2.3	2.7
	Ovarian ca. OVCAR-3	45.1	54.3
	Ovarian ca. SK-OV-3	88.9	87.1
	Ovarian ca. OVCAR-4	15.9	17.7
	Ovarian ca. OVCAR-5	29.9	29.1
	Ovarian ca. IGROV-1	54.0	50.3
	Ovarian ca. OVCAR-8	29.9	36.9
	Ovary	11.0	10.4
	Breast ca. MCF-7	0.0	0.0
	Breast ca. MDA-MB-231	0.0	29.7
	Breast ca. BT 549	88.3	100.0
	Breast ca. T47D	53.2	60.3
	Breast ca. MDA-N	13.6	17.2
	Breast Pool	7.6	9.7
	Trachea	3.5	4.7
	Lung	1.1	1.8
	Fetal Lung	14.0	18.7
	Lung ca. NCI-N417	3.3	2.9
	Lung ca. LX-1	1.5	2.2
	Lung ca. NCI-H146	0.0	0.0
	Lung ca. SHP-77	0.1	0.2
	Lung ca. A549	8.0	9.7
	Lung ca. NCI-H526	0.9	0.6
	Lung ca. NCI-H23	9.0	10.4
	Lung ca. NCI-H460	15.0	19.3
	Lung ca. HOP-62	15.4	20.9
	Lung ca. NCI-H522	1.8	2.0
	Liver	0.2	0.2
	Fetal Liver	1.8	2.4
	Liver ca. HepG2	0.0	0.0
	Kidney Pool	7.6	12.9
	Fetal Kidney	10.2	13.8
	Renal ca. 786-0	62.9	77.9
	Renal ca. A498	21.8	22.4
	Renal ca. ACHN	45.4	49.3
	Renal ca. UO-31	37.6	32.1
	Renal ca. TK-10	36.6	37.4
	Bladder	4.0	6.9
	Gastric ca. (liver met.) NCI-N87	1.8	2.7
	Gastric ca. KATO III	0.0	0.0
	Colon ca. SW-948	4.0	4.2
	Colon ca. SW480	7.5	9.1
	Colon ca.* (SW480 met) SW620	2.7	3.2
	Colon ca. HT29	1.3	2.3
	Colon ca. HCT-116	7.0	8.3
	Colon ca. CaCo-2	13.2	17.6
	Colon cancer tissue	6.3	6.7
	Colon ca. SW1116	0.1	0.0
	Colon ca. Colo-205	0.0	0.0
	Colon ca. SW-48	0.5	0.5
	Colon Pool	5.9	5.6
	Small Intestine Pool	4.2	4.1
	Stomach Pool	5.4	5.7
	Bone Marrow Pool	3.0	3.6
	Fetal Heart	1.7	1.7
	Heart Pool	3.1	3.1
	Lymph Node Pool	6.8	10.5
	Fetal Skeletal Muscle	2.4	2.1
	Skeletal Muscle Pool	1.6	1.4
	Spleen Pool	2.9	3.5
	Thymus Pool	5.6	5.8
	CNS cancer (glio/astro) U87-MG	25.0	31.0
	CNS cancer (glio/astro) U-118-MG	47.3	56.6
	CNS cancer (neuro; met) SK-N-AS	18.8	23.2
	CNS cancer (astro) SF-539	36.9	44.8
	CNS cancer (astro) SNB-75	100.0	100.0
	CNS cancer (glio) SNB-19	28.7	57.4
	CNS cancer (glio) SF-295	64.6	79.6
	Brain (Amygdala) Pool	0.4	0.3
	Brain (cerebellum)	1.2	1.3
	Brain (fetal)	6.9	9.0
	Brain (Hippocampus) Pool	0.8	0.6
	Cerebral Cortex Pool	0.5	0.5
	Brain (Substantia nigra) Pool	0.6	0.8
	Brain (Thalamus) Pool	0.9	0.8
	Brain (whole)	1.0	1.1
	Spinal Cord Pool	0.8	0.7
	Adrenal Gland	6.5	5.7
	Pituitary gland Pool	0.4	0.4
	Salivary Gland	1.5	1.4
	Thyroid (female)	1.8	1.8
	Pancreatic ca. CAPAN2	24.8	23.2
	Pancreas Pool	7.7	9.0
	Column A - Rel. Exp. (%) Ag271, Run 216607738
	Column B - Rel. Exp. (%) Ag271b, Run216607756

[0624]

TABLE BD
Panel 1
	Tissue Name	A	B	C
	Endothelial cells	11.0	5.0	3.9
	Endothelial cells (treated)	3.8	4.3	4.9
	Pancreas	2.7	3.1	1.9
	Pancreatic ca. CAPAN 2	38.2	24.0	19.8
	Adrenal gland	14.1	8.2	12.7
	Thyroid	8.6	6.1	4.5
	Salivary gland	3.5	4.1	3.3
	Pituitary gland	9.5	10.2	7.3
	Brain (fetal)	7.4	9.0	5.3
	Brain (whole)	0.8	3.7	1.3
	Brain (amygdala)	0.1	1.7	1.7
	Brain (cerebellum)	4.8	10.5	2.3
	Brain (hippocampus)	0.2	1.2	1.4
	Brain (substantia nigra)	0.9	3.5	2.1
	Brain (thalamus)	0.7	2.7	3.2
	Brain (hypothalamus)	0.5	3.4	3.3
	Spinal cord	2.1	4.0	3.6
	glio/astro U87-MG	30.8	24.0	27.4
	glio/astro U-118-MG	28.5	24.8	20.0
	astrocytoma SW1783	21.0	17.1	17.0
	neuro*; met SK-N-AS	24.1	17.6	29.9
	astrocytoma SF-539	35.6	27.4	41.2
	astrocytoma SNB-75	56.3	65.1	32.8
	glioma SNB-19	42.6	53.6	55.9
	glioma U251	39.8	26.8	48.3
	glioma SF-295	43.2	33.4	31.9
	Heart	15.2	4.5	6.8
	Skeletal muscle	0.1	1.9	4.6
	Bone marrow	1.1	1.7	2.1
	Thymus	28.1	18.9	10.2
	Spleen	2.5	5.1	3.2
	Lymph node	6.8	6.0	2.0
	Colon (ascending)	3.4	3.2	2.6
	Stomach	11.6	12.0	3.3
	Small intestine	5.9	8.7	5.5
	Colon ca. SW480	0.0	1.8	5.2
	Colon ca.* SW620 (SW480 met)	1.5	2.4	3.3
	Colon ca. HT29	0.1	1.7	3.2
	Colon ca. HCT-116	13.0	10.4	8.9
	Colon ca. CaCo-2	27.9	21.8	17.3
	Colon ca. HCT-15	1.7	5.0	7.3
	Colon ca. HCC-2998	0.4	1.2	2.7
	Gastric ca. * (liver met) NCI-N87	1.1	3.1	3.5
	Bladder	30.8	15.9	19.1
	Trachea	7.2	7.0	4.5
	Kidney	14.8	8.9	9.8
	Kidney (fetal)	53.6	55.9	27.7
	Renal ca. 786-0	94.6	96.6	70.2
	Renal ca. A498	65.5	65.5	46.3
	Renal ca. RXF 393	41.8	27.7	29.1
	Renal ca. ACHN	66.9	65.1	51.4
	Renal ca. UO-31	46.0	41.8	54.0
	Renal ca. TK-10	57.0	56.6	52.9
	Liver	2.0	3.3	4.4
	Liver (fetal)	2.0	2.4	2.9
	Liver ca. (hepatoblast) HepG2	0.0	0.0	0.0
	Lung	27.9	8.0	5.0
	Lung (fetal)	23.8	11.9	5.3
	Lung ca. (small cell) LX-1	0.0	1.4	3.2
	Lung ca. (small cell) NCI-H69	2.9	4.2	8.2
	Lung ca. (s. cell var.) SHP-77	0.0	0.4	0.2
	Lung ca. (large cell)NCI-H460	29.5	27.0	51.4
	Lung ca. (non-sm. cell)A549	6.6	7.1	12.2
	Lung ca. (non-s. cell) NCI-H23	6.6	7.1	17.2
	Lung ca. (non-s. cell) HOP-62	19.1	15.8	40.9
	Lung ca. (non-s. cl) NCI-H522	4.3	5.4	5.0
	Lung ca. (squam.) SW 900	15.8	17.1	19.1
	Lung ca. (squam.) NCI-H596	8.3	8.7	10.5
	Mammary gland	47.6	45.1	28.9
	Breast ca.* (pl. ef) MCF-7	0.0	0.0	0.0
	Breast ca.* (pl. ef) MDA-MB-231	17.1	15.1	18.4
	Breast ca.* (pl. ef) T47D	3.1	5.3	6.4
	Breast ca. BT-549	70.7	65.1	26.1
	Breast ca. MDA-N	43.8	25.7	35.4
	Ovary	54.0	39.5	27.9
	Ovarian ca. OVCAR-3	32.8	32.3	55.5
	Ovarian ca. OVCAR-4	39.2	33.0	46.0
	Ovarian ca. OVCAR-5	49.3	35.6	46.7
	Ovarian ca. OVCAR-8	39.5	20.0	57.4
	Ovarian ca. IGROV-1	46.0	48.0	100.0
	Ovarian ca. (ascites) SK-OV-3	53.2	47.6	68.8
	Uterus	36.6	9.9	9.4
	Placenta	18.2	23.8	11.7
	Prostate	6.4	6.7	4.3
	Prostate ca.* (bone met)PC-3	32.8	37.6	50.3
	Testis	27.7	23.8	4.7
	Melanoma Hs688(A).T	21.5	23.0	13.6
	Melanoma* (met) Hs688(B).T	25.3	25.3	20.3
	Melanoma UACC-62	28.1	23.0	58.2
	Melanoma M14	34.6	36.1	22.2
	Melanoma LOX IMVI	100.0	100.0	12.2
	Melanoma* (met) SK-MEL-5	12.1	10.9	14.3
	Melanoma SK-MEL-28	53.6	79.0	2.5
	Column A - Rel. Exp. (%) Ag271, Run 87588589
	Column B - Rel. Exp. (%) Ag271, Run 88706798
	Column C - Rel. Exp. (%) Ag271b, Run 97805788

[0625] General_screening_panel_v1.4 Summary: In this panel, the highest expression of this gene is seen in a sample derived from a brain cancer cell line, SNB-75 (CTs24). In addition, there is substantial expression in brain, renal, breast, ovarian and melanoma cancer cell lines. Thus, the expression of this gene can be used to distinguish cancer cells. Moreover, therapeutic modulation of this gene, through the use of small molecule drugs, antibodies or protein therapeutics will be beneficial for the treatmment of brain, renal, ovarian, breast cancers or melanoma.

[0626] This gene also has moderate and widespread expression in metabolic tissues including adipose, adult and fetal heart, adult and fetal skeletal muscle, adrenal, thyroid and pancreas. Thus, this gene product will bea useful target for the treatment of metabolic and endocrine disease, including obesity and Types 1 and 2 diabetes. This gene is differentially expressed in fetal (CTs=29-30) vs adult liver (CTs=33). The higher expression in fetal liver suggests that this gene product will be involved in the development of the liver. Therefore, this gene product will be useful in restoring mass or function to the adult liver.

[0627] This panel also shows low but significant levels of expression of this gene in the CNS.

[0628] Panel 1 Summary: Similar to panel 1.4, highest expression of this gene is consistently seen in a number of cancer cell lines including: ovarian, pancreatic, prostate, renal carcinomas, melanoma, and CNS cancers, when compared to normal controls. There is differential expression between adult and fetal normal kidney tissues. Inhibition of expression or function of this gene or gene product will be of therapeutic value for the treatment of cancer or other disease that involve cell proliferation. Furthermore, targeting the gene product, i.e. with a monoclonal antibody is anticipated to limit or block the extent of tumor cell migration, invasion and-tumor metastasis, particularly in melanomas, prostate, pancreatic, ovarian and renal cell carcinomas and CNS cancers. This gene and/or gene product is an effective marker for the diagnosis and detection of a variety of cancers. This gene is also expressed at comparatively low levels in all CNS tissues examined.

C. NOV 3, CG51514: Slit-3-Like

[0629] Expression of gene CG51514-01 was assessed using the primer-probe sets Ag1004, Ag1026 and Gpcr38, described in Tables CA, CB and CC. Results of the RTQ-PCR runs are shown in Tables CD, CE and CF.

TABLE CA
Probe Name Ag1004
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-aaccaaaatcttggacctcagt-3′	22	174	177
Probe	TET-5′-aaaagcgtcaaccctgaagaattcat-3′-	26	208	178
	TAMRA
Reverse	5′-tctcttccagcagaggatatga-3′	22	235	179

[0630]

TABLE CB
Probe Name Ag1026
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-cagttaaggaggctgtgaaggt-3′	22	1477	180
Probe	TET-5′-attcccagcagcattgctagcgat-3′-	24	1450	181
	TAMRA
Reverse	5′-gatcaagacagcgggatgtat-3′	21	1423	182

[0631]

TABLE CC
Probe Name Gpcr38
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-tgttggtactgctgttaagttgca-3′	24	559	240
Probe	TET-5′-tctccagggtgagctgctccaagc-3′-	24	533	241
	TAMRA
Reverse	5′-agggcattcagtgggcttct-3′	20	511	242

[0632]

TABLE CD
General_screening_panel_v1.6
Tissue Name                      A
Adipose                          0.1
Melanoma* Hs688(A).T             0.3
Melanoma* Hs688(B).T             1.0
Melanoma* M14                    1.2
Melanoma* LOXIMVI                0.9
Melanoma* SK-MEL-5               0.4
Squamous cell carcinoma SCC-4    0.0
Testis Pool                      3.5
Prostate ca.* (bone met) PC-3    5.9
Prostate Pool                    2.1
Placenta                         0.1
Uterus Pool                      5.3
Ovarian ca. OVCAR-3              3.1
Ovarian ca. SK-OV-3              0.7
Ovarian ca. OVCAR-4              0.0
Ovarian ca. OVCAR-5              0.0
Ovarian ca. IGROV-1              8.4
Ovarian ca. OVCAR-8              6.0
Ovary                            0.1
Breast ca. MCF-7                 0.0
Breast ca. MDA-MB-231            0.0
Breast ca. BT 549                74.7
Breast ca. T47D                  0.0
Breast ca. MDA-N                 0.9
Breast Pool                      32.3
Trachea                          0.5
Lung                             0.1
Fetal Lung                       0.4
Lung ca. NCI-N417                2.8
Lung ca. LX-1                    0.0
Lung ca. NCI-H146                57.0
Lung ca. SHP-77                  9.0
Lung ca. A549                    0.0
Lung ca. NCI-H526                0.3
Lung ca. NCI-H23                 0.0
Lung ca. NCI-H460                0.5
Lung ca. HOP-62                  0.5
Lung ca. NCI-H522                0.0
Liver                            0.0
Fetal Liver                      0.1
Liver ca. HepG2                  0.1
Kidney Pool                      49.0
Fetal Kidney                     10.0
Renal ca. 786-0                  0.0
Renal ca. A498                   0.3
Renal ca. ACHN                   0.5
Renal ca. UO-31                  6.8
Renal ca. TK-10                  2.1
Bladder                          0.5
Gastric ca. (liver met.) NCI-N87 0.0
Gastric ca. KATO III             0.0
Colon ca. SW-948                 0.0
Colon ca. SW480                  0.0
Colon ca.* (SW480 met) SW620     0.0
Colon ca. HT29                   0.0
Colon ca. HCT-116                0.0
Colon ca. CaCo-2                 0.4
Colon cancer tissue              0.1
Colon ca. SW1116                 0.0
Colon ca. Colo-205               0.0
Colon ca. SW-48                  0.0
Colon Pool                       50.3
Small Intestine Pool             16.3
Stomach Pool                     7.5
Bone Marrow Pool                 26.1
Fetal Heart                      0.4
Heart Pool                       18.6
Lymph Node Pool                  54.3
Fetal Skeletal Muscle            1.7
Skeletal Muscle Pool             0.0
Spleen Pool                      0.4
Thymus Pool                      3.6
CNS cancer (glio/astro) U87-MG   14.2
CNS cancer (glio/astro) U-118-MG 0.0
CNS cancer (neuro; met) SK-N-AS  26.4
CNS cancer (astro) SF-539        0.0
CNS cancer (astro) SNB-75        3.3
CNS cancer (glio) SNB-19         6.8
CNS cancer (glio) SF-295         100.0
Brain (Amygdala) Pool            13.1
Brain (cerebellum)               3.4
Brain (fetal)                    39.2
Brain (Hippocampus) Pool         16.4
Cerebral Cortex Pool             31.9
Brain (Substantia nigra) Pool    12.0
Brain (Thalamus) Pool            25.9
Brain (whole)                    33.9
Spinal Cord Pool                 5.1
Adrenal Gland                    0.3
Pituitary gland Pool             1.0
Salivary Gland                   0.0
Thyroid (female)                 2.8
Pancreatic ca. CAPAN2            0.0
Pancreas Pool                    0.3
Column A - Rel. Exp. (%) Ag1026, Run 277226628

[0633]

TABLE CE
Panel 1.1
Tissue Name                     A
Adrenal gland                   1.2
Bladder                         1.7
Brain (amygdala)                6.2
Brain (cerebellum)              19.8
Brain (hippocampus)             14.0
Brain (substantia nigra)        13.1
Brain (thalamus)                16.7
Cerebral Cortex                 57.4
Brain (fetal)                   29.1
Brain (whole)                   26.8
glio/astro U-118-MG             0.0
astrocytoma SF-539              0.0
astrocytoma SNB-75              11.4
astrocytoma SW1783              0.0
glioma U251                     12.9
glioma SF-295                   71.7
glioma SNB-19                   43.8
glio/astro U87-MG               20.2
neuro*; met SK-N-AS             41.8
Mammary gland                   0.6
Breast ca. BT-549               7.9
Breast ca. MDA-N                4.4
Breast ca.* (pl.ef) T47D        0.7
Breast ca.* (pl.ef) MCF-7       0.0
Breast ca.* (pl.ef) MDA-MB-231  0.0
Small intestine                 0.7
Colorectal                      0.2
Colon ca. HT29                  0.3
Colon ca. CaCo-2                0.6
Colon ca. HCT-15                0.8
Colon ca. HCT-116               0.0
Colon ca. HCC-2998              0.0
Colon ca. SW480                 0.0
Colon ca.* SW620 (SW480 met)    0.0
Stomach                         2.5
Gastric ca. (liver met) NCI-N87 0.2
Heart                           1.0
Skeletal muscle (Fetal)         2.6
Skeletal muscle                 0.1
Endothelial cells               0.0
Heart (Fetal)                   0.4
Kidney                          11.6
Kidney (fetal)                  3.7
Renal ca. 786-0                 0.0
Renal ca. A498                  1.3
Renal ca. ACHN                  0.9
Renal ca. TK-10                 4.6
Renal ca. UO-31                 10.4
Renal ca. RXF 393               0.4
Liver                           0.1
Liver (fetal)                   0.0
Liver ca. (hepatoblast) HepG2   0.0
Lung                            0.1
Lung (fetal)                    0.3
Lung ca. (non-s.cell) HOP-62    5.4
Lung ca. (large cell) NCI-H460  1.4
Lung ca. (non-s.cell) NCI-H23   0.0
Lung ca. (non-s.cl) NCI-H522    0.0
Lung ca. (non-sm. cell) A549    7.1
Lung ca. (s.cell var.) SHP-77   5.3
Lung ca. (small cell) LX-1      0.0
Lung ca. (small cell) NCI-H69   100.0
Lung ca. (squam.) SW 900        9.0
Lung ca. (squam.) NCI-H596      55.9
Lymph node                      0.0
Spleen                          0.5
Thymus                          0.1
Ovary                           2.2
Ovarian ca. IGROV-1             0.2
Ovarian ca. OVCAR-3             6.1
Ovarian ca. OVCAR-4             0.1
Ovarian ca. OVCAR-5             2.5
Ovarian ca. OVCAR-8             8.3
Ovarian ca.* (ascites) SK-OV-3  1.1
Pancreas                        6.3
Pancreatic ca. CAPAN 2          0.0
Pituitary gland                 4.7
Placenta                        1.8
Prostate                        1.3
Prostate ca.* (bone met) PC-3   10.1
Salivary gland                  1.2
Trachea                         0.6
Spinal cord                     2.8
Testis                          5.2
Thyroid                         14.9
Uterus                          0.0
Melanoma M14                    5.5
Melanoma LOX IMVI               1.1
Melanoma UACC-62                0.1
Melanoma SK-MEL-28              20.7
Melanoma* (met) SK-MEL-5        0.5
Melanoma Hs688 (A).T            0.0
Melanoma* (met) Hs688(B).T      0.6
Column A - Rel. Exp. (%) Gpcr38, Run 109649891

[0634]

TABLE CF
Panel 4.1D
Tissue Name                      A
Secondary Th1 act                0.0
Secondary Th2 act                0.0
Secondary Tr1 act                0.0
Secondary Th1 rest               0.0
Secondary Th2 rest               0.0
Secondary Tr1 rest               0.0
Primary Th1 act                  0.0
Primary Th2 act                  0.0
Primary Tr1 act                  0.0
Primary Th1 rest                 0.0
Primary Th2 rest                 0.0
Primary Tr1 rest                 0.0
CD45RA CD4 lymphocyte act        0.0
CD45RO CD4 lymphocyte act        0.0
CD8 lymphocyte act               0.0
Secondary CD8 lymphocyte rest    0.0
Secondary CD8 lymphocyte act     0.0
CD4 lymphocyte none              0.0
2ry Th1/Th2/Tr1_anti-CD95 CH11   0.0
LAK cells rest                   0.0
LAK cells IL-2                   1.4
LAK cells IL-2 + IL-12           0.0
LAK cells IL-2 + IFN gamma       0.0
LAK cells IL-2 + IL-18           0.6
LAK cells PMA/ionomycin          0.0
NK Cells IL-2 rest               24.0
Two Way MLR 3 day                5.8
Two Way MLR 5 day                0.0
Two Way MLR 7 day                0.0
PBMC rest                        0.0
PBMC PWM                         0.0
PBMC PHA-L                       0.0
Ramos (B cell) none              0.0
Ramos (B cell) ionomycin         0.0
B lymphocytes PWM                0.0
B lymphocytes CD40L and IL-4     0.0
EOL-1 dbcAMP                     0.0
EOL-1 dbcAMP PMA/ionomycin       0.0
Dendritic cells none             1.4
Dendritic cells LPS              0.0
Dendritic cells anti-CD40        1.4
Monocytes rest                   0.0
Monocytes LPS                    1.4
Macrophages rest                 0.0
Macrophages LPS                  0.0
HUVEC none                       0.0
HUVEC starved                    0.0
HUVEC IL-1beta                   0.0
HUVEC IFN gamma                  1.5
HUVEC TNF alpha + IFN gamma      0.0
HUVEC TNF alpha + IL4            0.0
HUVEC IL-11                      0.0
Lung Microvascular EC none       0.0
Lung Microvascular EC TNFalpha + IL-1 beta 0.0
Microvascular Dermal EC none     0.0
Microsvasular Dermal EC TNFalpha + IL-1 beta 0.0
Bronchial epithelium TNFalpha + IL1 beta 1.6
Small airway epithelium none     1.2
Small airway epithelium TNFalpha + IL-1 beta 0.0
Coronery artery SMC rest         1.1
Coronery artery SMC TNFalpha + IL-1 beta 0.0
Astrocytes rest                  1.4
Astrocytes TNFalpha + IL-1 beta  3.3
KU-812 (Basophil) rest           64.6
KU-812 (Basophil) PMA/ionomycin  100.0
CCD1106 (Keratinocytes) none     0.0
CCD1106 (Keratinocytes) TNFalpha + IL-1beta 5.5
Liver cirrhosis                  0.0
NCI-H292 none                    0.0
NCI-H292 IL-4                    0.0
NCI-H292 IL-9                    1.8
NCI-H292IL-13                    1.1
NCI-H292 IFN gamma               0.0
HPAEC none                       0.0
HPAEC TNF alpha + IL-1beta       0.0
Lung fibroblast none             0.0
Lung fibroblast TNF alpha + IL-1beta 0.0
Lung fibroblast IL-4             0.0
Lung fibroblast IL-9             0.0
Lung fibroblast IL-13            0.0
Lung fibroblast IFN gamma        0.0
Dermal fibroblast CCD1070 rest   0.0
Dermal fibroblast CCD1070 TNF alpha 0.0
Dermal fibroblast CCD1070 IL-1 beta 0.0
Dermal fibroblast IFN gamma      0.0
Dermal fibroblast IL-4           0.0
Dermal Fibroblasts rest          0.0
Neutrophils TNFa + LPS           0.0
Neutrophils rest                 0.0
Colon                            0.0
Lung                             1.4
Thymus                           0.0
Kidney                           11.1
Column A - Rel. Exp. (%) Ag1026, Run 268700628

[0635] General_screening_panel_v1.6 Summary: In this panel, the highest expression of this gene is seen in a brain cancer SF-295 cell line (CT=27). High to moderate expression is seen in all the regions of central nervous system examined, some tissues with metabolic/endocrine functions and also in number of cancer cell lines derived from brain, melanoma, renal, breast, ovarian and lung cancers. This expression pattern correlates with that seen in panel 1.1.

[0636] Panel 1.1 Summary: In this panel, gene expression is highest in NCI-H69 lung cancer cell line (CT23.9), is also significantly over-expressed in other lung cancer cell lines relative to the normal lung and is highly expressed by brain tumor and melanoma cell lines.

[0637] The gene and/or its product can therefore be used as a marker or diagnostic for these cancers. Therapeutic modulation of the activity of the this gene or its protein product will be of use in the treatment of CNS malignancies, melanomas and/or lung cancer.

[0638] Among metabolically relevant tissues, gene expression is seen in fetal skeletal muscle, pancreas, and pituitary gland. This observation suggests that therapeutic modulation will aid the treatment of metabolic diseases such as obesity and diabetes as well as neuroendocrine disorders.

[0639] In addition, there appears to be significant expression of this gene in uterus, ovary and testis tissue

[0640] Panel 4.1D Summary: This gene shows expression mainly in resting and activated basophils (CTs=32-32.6). Basophils release histamines and other biological modifiers in reponse to allergens and play an important role in the pathology of asthma and hypersensitivity reactions. Therefore, therapeutics designed against the putative protein encoded by this gene will reduce or inhibit inflammation by blocking basophil function in these diseases. In addition, these cells are a reasonable model for the inflammatory cells that take part in various inflammatory lung and bowel diseases, such as asthma, Crohn's disease, and ulcerative colitis. Low expression of this gene is also seen in resting IL-2 treated NK cells. Therefore, therapeutics that modulate the function of this gene product will reduce or eliminate the symptoms of patients suffering from asthma, Crohn's disease, and ulcerative colitis.

D. NOV 4, CG52053-01

[0641] Expression of gene CG52053-01 was assessed using the primer-probe sets Ag2823, Ag168, Ag66, Ag33, Ag168fam described in Tables DA, DB, DC, DD, DE. Results of the RTQ-PCR runs are shown in Tables DH, DI, DJ.

TABLE DA
Probe Name Ag2823
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gtcatggcaagaagatcttgag-3′	22	515	183
Probe	TET-5′-atgtatctggacacccctcggtatcg-3′-	26	540	184
	TAMRA
Reverse	5′-caacttttgacttccggtcat-3′	21	580	185

[0642]

TABLE DB
Probe Name Ag168
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gcatgtgcaggacctccagt-3′-	20	760	186
Probe	TET-5═-cagttccacagccacaatttcctccac-3′	27	730	187
	TAMRA
Reverse	5′-tccacgttgcctcctcgt-3′	18	704	188

[0643]

TABLE DC
Probe Name Ag66
			Start	SEQ
Primers	Sequences	Length	Position	ID No
Forward	5′-cacaaggaagttcctccaaggata-3′	24	222	189
Probe	TET-5′-	35	252	190
	agaacgaaccaaattaaaatcacattcaagtccga-3′-
	TAMRA
Reverse	5′-aatccaggtttagccacaaagtagtc-3′	26	288	191

[0644]

TABLE DD
Probe Name Ag33
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-cgcttggcatcatcattgag-3′	20	612	192
Probe	TET-5′-tccaggtcaacttttgacttccggtca-3′-	27	581	193
	TAMRA
Reverse	5′-cggtatcgaggcaggtcatac-3′	21	558	194

[0645]

TABLE DE
Probe Name Ag168fam
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gcatgtgcaggacctccagt-3′	20	760	195
Probe	TET-5′-cagttccacagccacaatttcctccac-3′-	27	730	196
	TAMRA
Reverse	5′-tccacgttgcctcctcgt-3′	18	704	197

[0646]

TABLE DF
Oncology_cell_line_screening_panel_v3.1
Tissue Name                      A
Daoy Medulloblastoma/Cerebellum  0.0
TE671 Medulloblastom/Cerebellum  4.1
D283 Med Medulloblastoma/Cerebellum 0.4
PFSK-1 Primitive Neuroectodermal/Cerebellum 0.8
XF-498_CNS                       1.1
SNB-78_CNS/glioma                0.0
SF-268_CNS/glioblastoma          0.1
T98G_Glioblastoma                100.0
SK-N-SH_Neuroblastoma (metastasis) 12.9
SF-295_CNS/glioblastoma          22.1
Cerebellum                       1.2
Cerebellum                       0.7
NCI-H292_Mucoepidermoid lung ca. 3.1
DMS-114_Small cell lung cancer   0.1
DMS-79_Small cell lung cancer/neuroendocrine 0.0
NCI-H146_Small cell lung cancer/neuroendocrine 4.0
NCI-H526_Small cell lung cancer/neuroendocrine 0.0
NCI-N417_Small cell lung cancer/neuroendocrine 2.1
NCI-H82_Small cell lung cancer/neuroendocrine 0.3
NCI-H157_Squamous cell lung cancer (metastasis) 1.9
NCI-H1155_Large cell lung cancer/neuroendocrine 0.7
NCI-H1299_Large cell lung cancer/neuroendocrine 1.1
NCI-H727_Lung carcinoid          0.1
NCI-UMC-11_Lung carcinoid        28.3
LX-1 Small cell lung cancer      0.0
Colo-205_Colon cancer            0.0
KM12_Colon cancer                0.0
KM20L2_Colon cancer              0.0
NCI-H716_Colon cancer            1.0
SW-48_Colon adenocarcinoma       0.0
SW1116_Colon adenocarcinoma      0.0
LS 174T_Colon adenocarcinoma     0.0
SW-948_Colon adenocarcinoma      0.0
SW-480_Colon adenocarcinoma      0.0
NCI-SNU-5_Gastric ca.            0.0
KATO III_Stomach                 0.0
NCI-SNU-16_Gastric ca.           0.2
NCI-SNU-1_Gastric ca.            0.0
RF-1_Gastric adenocarcinoma      0.2
RF-48_Gastric adenocarcinoma     0.5
MKN-45_Gastric ca.               0.0
NCI-N87_Gastric ca.              0.0
OVCAR-5_Ovarian ca.              0.3
RL95-2_Uterine carcinoma         1.4
HelaS3_Cervical adenocarcinoma   0.0
Ca Ski_Cervical epidermoid carcinoma (metastasis) 1.9
ES-2_Ovarian clear cell carcinoma 1.4
Ramos/6h stim_Stimulated with PMA/ionomycin 6h 12.6
Ramos/14h stim_Stimulated with PMA/ionomycin 14h 11.3
MEG-01_Chronic myelogenous leukemia (megokaryoblast) 12.2
Raji_Burkitt's lymphoma          1.1
Daudi_Burkitt's lymphoma         7.6
U266_B-cell plasmacytoma/myeloma 0.0
CA46_Burkitt's lymphoma          1.6
RL_non-Hodgkin's B-cell lymphoma 2.0
JM1_pre-B-cell lymphoma/leukemia 0.2
Jurkat_T cell leukemia           0.0
TF-1_Erythroleukemia             8.4
HUT 78_T-cell lymphoma           0.2
U937_Histiocytic lymphoma        0.0
KU-812_Myelogenous leukemia      6.0
769-P_Clear cell renal ca.       0.2
Caki-2_Clear cell renal ca.      3.8
SW 839_Clear cell renal ca.      0.5
G401_Wilms' tumor                0.6
Hs766T_Pancreatic ca. (LN metastasis) 0.0
CAPAN-1_Pancreatic adenocarcinoma (liver metastasis) 0.3
SU86.86_Pancreatic carcinoma (liver metastasis) 2.1
BxPC-3_Pancreatic adenocarcinoma 0.0
HPAC_Pancreatic adenocarcinoma   5.9
MIA PaCa-2_Pancreatic ca.        0.1
CFPAC-1_Pancreatic ductal adenocarcinoma 9.7
PANC-1_Pancreatic epithelioid ductal ca. 0.1
T24_Bladder ca. (transitional cell) 0.2
5637_Bladder ca.                 1.0
HT-1197_Bladder ca.              1.9
UM-UC-3_Bladder ca. (transitional cell) 0.0
A204_Rhabdomyosarcoma            0.0
HT-1080_Fibrosarcoma             0.0
MG-63_Osteosarcoma (bone)        0.2
SK-LMS-1_Leiomyosarcoma (vulva)  0.1
SJRH30_Rhabdomyosarcoma (met to bone marrow) 6.1
A431_Epidermoid ca.              3.6
WM266-4_Melanoma                 0.8
DU 145_Prostate                  0.7
MDA-MB-468_Breast adenocarcinoma 0.0
SSC-4_Tongue                     0.0
SSC-9_Tongue                     0.8
SSC-15_Tongue                    0.2
CAL 27_Squamous cell ca. of tongue 0.0
Column A - Rel. Exp. (%) Ag66, Run 224996569

[0647]

TABLE DG
Panel 1.3D
Tissue Name                      A
Liver adenocarcinoma             1.1
Pancreas                         17.0
Pancreatic ca. CAPAN 2           0.6
Adrenal gland                    55.9
Thyroid                          5.3
Salivary gland                   6.7
Pituitary gland                  38.7
Brain (fetal)                    2.1
Brain (whole)                    4.0
Brain (amygdala)                 2.5
Brain (cerebellum)               0.4
Brain (hippocampus)              4.4
Brain (substantia nigra)         0.3
Brain (thalamus)                 1.7
Cerebral Cortex                  0.7
Spinal cord                      6.3
glio/astro U87-MG                0.0
glio/astro U-118-MG              0.3
astrocytoma SW1783               8.5
neuro*; met SK-N-AS              3.8
astrocytoma SF-539               0.5
astrocytoma SNB-75               6.5
glioma SNB-19                    5.0
glioma U251                      22.8
glioma SF-295                    100.0
Heart (fetal)                    1.2
Heart                            16.2
Skeletal muscle (fetal)          1.5
Skeletal muscle                  10.4
Bone marrow                      2.4
Thymus                           1.4
Spleen                           2.4
Lymph node                       9.9
Colorectal                       1.7
Stomach                          12.5
Small intestine                  13.6
Colon ca. SW480                  0.0
Colon ca.* SW620(SW480 met)      0.2
Colon ca. HT29                   0.0
Colon ca.HCT-116                 0.0
Colon ca. CaCo-2                 0.0
Colon ca. tissue(ODO3866)        1.3
Colon ca. HCC-2998               0.5
Gastric ca.* (liver met) NCI-N87 0.4
Bladder                          35.6
Trachea                          3.4
Kidney                           4.0
Kidney (fetal)                   5.1
Renal ca. 786-0                  0.0
Renal ca. A498                   2.3
Renal ca. RXF 393                0.2
Renal ca. ACHN                   0.9
Renal ca. UO-31                  1.6
Renal ca. TK-10                  1.3
Liver                            0.5
Liver (fetal)                    0.9
Liver ca. (hepatoblast) HepG2    0.0
Lung                             1.7
Lung (fetal)                     1.3
Lung ca. (small cell) LX-1       0.0
Lung ca. (small cell) NCI-H69    0.0
Lung ca. (s.cell var.) SHP-77    6.6
Lung ca. (large cell)NCI-H460    0.3
Lung ca. (non-sm. cell) A549     6.5
Lung ca. (non-s.cell) NCI-H23    0.3
Lung ca. (non-s.cell) HOP-62     4.8
Lung ca. (non-s.cl) NCI-H522     0.0
Lung ca. (squam.) SW 900         12.0
Lung ca. (squam.) NCI-H596       8.4
Mammary gland                    16.5
Breast ca.* (pl.ef) MCF-7        0.0
Breast ca.* (pl.ef) MDA-MB-231   0.0
Breast ca.* (pl.ef) T47D         0.0
Breast ca. BT-549                4.5
Breast ca. MDA-N                 0.0
Ovary                            4.2
Ovarian ca. OVCAR-3              0.7
Ovarian ca. OVCAR-4              0.1
Ovarian ca. OVCAR-5              91.4
Ovarian ca. OVCAR-8              2.6
Ovarian ca. IGROV-1              2.0
Ovarian ca.* (ascites) SK-OV-3   0.2
Uterus                           17.3
Placenta                         8.1
Prostate                         2.1
Prostate ca.* (bone met)PC-3     1.8
Testis                           4.8
Melanoma Hs688(A).T              0.7
Melanoma* (met) Hs688(B).T       0.4
Melanoma UACC-62                 2.2
Melanoma M14                     1.6
Melanoma LOX IMVI                0.0
Melanoma* (met) SK-MEL-5         1.4
Adipose                          16.0
Column A - Rel. Exp. (%) Ag2823, Run 165518946

[0648]

TABLE DH
Panel 2D
Tissue Name	A	B	C	D
Normal Colon	33.9	22.1	18.4	19.6
CC Well to Mod Diff	2.9	1.6	1.5	1.3
(ODO3866)
CC Margin	2.0	3.5	2.1	2.9
(ODO3866)
CC Gr.2 rectosigmoid	1.4	0.6	0.4	0.5
(ODO3868)
CC Margin	1.5	0.6	0.7	1.3
(ODO3868)
CC Mod Diff	3.2	2.3	1.4	1.6
(ODO3920)
CC Margin	5.3	3.5	1.6	4.7
(ODO3920)
CC Gr.2 ascend colon	8.2	8.2	5.3	6.3
(ODO3921)
CC Margin	4.2	3.3	2.3	4.2
(ODO3921)
CC from Partial	2.6	3.6	7.5	2.7
Hepatectomy
(ODO4309) Mets
Liver Margin	1.7	2.7	2.2	1.9
(ODO4309)
Colon mets to lung	0.8	1.0	0.5	0.6
(OD04451-01)
Lung Margin	4.1	2.4	1.6	2.5
(OD04451-02)
Normal Prostate	5.3	4.5	20.2	3.7
6546-1
Prostate Cancer	10.2	9.1	4.1	4.4
(OD04410)
Prostate Margin	8.8	10.3	6.9	8.5
(OD04410)
Prostate Cancer	11.7	17.0	10.0	14.4
(OD04720-01)
Prostate Margin	31.4	19.1	16.3	18.3
(OD04720-02)
Normal Lung	6.3	9.1	6.4	11.0
061010
Lung Met to	1.1	0.5	0.8	1.4
Muscle (ODO4286)
Muscle Margin	8.1	10.2	5.8	9.9
(ODO4286)
Lung Malignant	11.5	8.8	6.8	9.2
Cancer (OD03126)
Lung Margin	3.5	3.7	2.3	3.5
(OD03126)
Lung Cancer	2.2	2.7	1.1	2.6
(OD04404)
Lung Margin	7.2	8.9	5.5	6.6
(OD04404)
Lung Cancer	3.2	2.5	1.1	1.8
(OD04565)
Lung Margin	2.2	3.2	0.9	0.8
(OD04565)
Lung Cancer	4.2	4.8	4.0	4.1
(OD04237-01)
Lung Margin	7.9	6.4	6.3	7.6
(OD04237-02)
Ocular Mel Met	5.6	6.9	6.6	5.6
to Liver (ODO4310)
Liver Margin	1.8	1.3	0.9	2.2
(ODO4310)
Melanoma Mets to	0.6	0.5	0.4	0.5
Lung (OD04321)
Lung Margin	1.6	1.7	2.1	1.8
(OD04321)
Normal Kidney	17.0	19.8	13.7	18.7
Kidney Ca, Nuclear	11.0	14.9	6.7	11.6
grade 2 (OD04338)
Kidney Margin	12.6	11.8	5.0	10.7
(OD04338)
Kidney Ca Nuclear	19.8	17.1	11.2	16.5
grade 1/2 (OD04339)
Kidney Margin	8.7	8.8	7.4	10.4
(OD04339)
Kidney Ca, Clear	100.0	100.0	100.0	100.0
cell type (OD04340)
Kidney Margin	9.6	11.5	9.5	10.7
(OD04340)
Kidney Ca, Nuclear	6.9	4.5	3.9	4.7
grade 3 (OD04348)
Kidney Margin	4.7	5.3	4.1	4.5
(OD04348)
Kidney Cancer	11.7	10.4	8.0	9.2
(OD04622-01)
Kidney Margin	0.8	1.2	0.6	1.0
(OD04622-03)
Kidney Cancer	9.5	5.5	9.0	10.2
(OD04450-01)
Kidney Margin	11.2	11.5	7.0	7.7
(OD04450-03)
Kidney Cancer	0.9	0.9	0.7	2.3
8120607
Kidney Margin	0.9	0.9	0.4	1.3
8120608
Kidney Cancer	1.0	1.0	1.2	1.6
8120613
Kidney Margin	0.7	1.0	0.8	1.0
8120614
Kidney Cancer	11.0	10.5	7.9	10.1
9010320
Kidney Margin	1.5	2.1	1.4	2.4
9010321
Normal Uterus	7.8	9.5	5.2	6.3
Uterus Cancer	13.7	11.7	11.0	14.0
064011
Normal Thyroid	15.3	16.4	10.2	16.6
Thyroid Cancer	5.8	7.5	4.1	6.2
064010
Thyroid Cancer	6.2	5.2	3.9	7.3
A302152
Thyroid Margin	14.7	13.7	9.3	17.0
A302153
Normal Breast	36.3	39.2	0.0	50.7
Breast Cancer	5.6	5.4	1.7	4.2
(OD04566)
Breast Cancer	17.2	17.6	10.8	13.6
(OD04590-01)
Breast Cancer Mets	19.6	21.5	14.0	21.0
(OD04590-03)
Breast Cancer	4.0	4.7	3.0	4.6
Metastasis (OD04655-05)
Breast Cancer	6.2	6.3	3.0	4.5
064006
Breast Cancer	17.3	18.8	9.9	17.9
1024
Breast Cancer	8.8	9.8	8.5	8.5
9100266
Breast Margin	13.5	15.6	14.5	14.5
9100265
Breast Cancer	37.1	40.3	20.6	32.5
A209073
Breast Margin	28.9	22.5	14.6	22.2
A209073
Normal Liver	1.2	1.1	1.4	0.9
Liver Cancer 064003	1.9	1.8	1.2	1.8
Liver Cancer 1025	0.6	0.8	0.9	1.5
Liver Cancer 1026	0.4	0.9	0.9	1.3
Liver Cancer 6004-T	1.1	1.9	0.4	1.2
Liver Tissue 6004-N	1.4	2.2	0.6	1.1
Liver Cancer 6005-T	0.5	1.0	0.9	1.0
Liver Tissue 6005-N	0.6	0.4	0.2	0.2
Normal Bladder	85.9	68.3	53.6	66.0
Bladder Cancer 1023	1.6	2.0	0.7	2.0
Bladder Cancer	8.1	9.5	6.3	6.6
A302173
Bladder Cancer	1.6	1.8	1.0	1.3
(OD04718-01)
Bladder Normal	14.2	11.0	8.5	12.4
Adjacent (OD04718-03)
Normal Ovary	7.9	9.5	5.3	8.6
Ovarian Cancer	89.5	66.9	47.0	65.1
064008
Ovarian Cancer	15.0	12.0	9.0	14.3
(OD04768-07)
Ovary Margin	8.3	9.3	4.1	5.3
(OD04768-08)
Normal Stomach	24.7	19.5	15.9	20.0
Gastric Cancer	2.7	3.8	2.6	3.7
9060358
Stomach Margin	14.9	11.2	10.4	10.5
9060359
Gastric Cancer	8.1	7.6	4.0	7.6
9060395
Stomach Margin	8.5	10.2	8.4	10.4
9060394
Gastric Cancer	6.0	5.5	5.0	5.3
9060397
Stomach Margin	3.4	2.8	2.5	3.1
9060396
Gastric Cancer	8.3	7.3	13.4	5.7
064005
Column A - Rel. Exp. (%) Ag168fam, Run 157415982
Column B - Rel. Exp. (%) Ag168fam, Run 157543473
Column C - Rel. Exp. (%) Ag2823, Run 163578436
Column D - Rel. Exp. (%) Ag33, Run 157413196

[0649]

TABLE DI
Panel 4D
Tissue Name	A	B	C	D	E
Secondary Th1 act	0.5	0.3	0.1	0.2	0.4
Secondary Th2 act	0.1	0.0	0.0	0.2	0.0
Secondary Tr1 act	0.1	0.2	0.0	0.0	0.2
Secondary Th1 rest	0.1	0.0	0.0	0.1	0.2
Secondary Th2 rest	0.1	0.0	0.0	0.0	0.0
Secondary Tr1 rest	0.0	0.0	0.0	0.0	0.0
Primary Th1 act	0.0	0.1	0.0	0.0	0.0
Primary Th2 act	0.0	0.0	0.1	0.0	0.1
Primary Tr1 act	0.0	0.1	0.0	0.0	0.0
Primary Th1 rest	0.3	0.2	0.0	0.5	0.1
Primary Th2 rest	0.1	0.0	0.0	0.0	0.0
Primary Tr1 rest	0.1	0.0	0.1	0.2	0.0
CD45RA CD4 lymphocyte act	0.6	0.8	1.3	0.5	0.7
CD45RO CD4 lymphocyte act	0.3	0.9	0.4	1.5	1.0
CD8 lymphocyte act	0.8	1.4	1.4	1.4	1.9
Secondary CD8 lymphocyte rest	0.1	0.3	0.6	0.3	0.2
Secondary CD8 lymphocyte act	1.0	1.4	1.2	0.8	0.8
CD4 lymphocyte none	0.7	1.2	0.7	1.3	0.8
2ry Th1/Th2/Tr1_anti-CD95 CH11	0.5	0.7	0.2	0.3	0.0
LAK cells rest	2.1	3.2	2.1	2.6	1.1
LAK cells IL-2	9.7	12.0	11.4	9.7	6.6
LAK cells IL-2 + IL-12	1.7	2.7	1.4	2.3	2.1
LAK cells IL-2 + IFN gamma	3.5	5.2	2.5	3.9	3.6
LAK cells IL-2 + IL-18	2.2	1.9	1.4	0.5	2.9
LAK cells PMA/ionomycin	0.6	0.8	0.3	0.6	0.4
NK Cells IL-2 rest	10.2	8.0	10.2	11.3	12.4
Two Way MLR 3 day	3.1	4.1	4.0	3.0	3.5
Two Way MLR 5 day	0.6	0.9	1.3	0.9	0.5
Two Way MLR 7 day	0.5	0.6	1.0	0.9	0.3
PBMC rest	3.9	3.4	4.3	3.5	1.9
PBMC PWM	0.9	0.6	0.6	0.8	0.8
PBMC PHA-L	0.5	0.7	0.1	1.3	0.3
Ramos (B cell) none	57.8	62.4	32.5	53.2	22.7
Ramos (B cell) ionomycin	100.0	100.0	100.0	100.0	100.0
B lymphocytes PWM	12.3	11.3	13.1	10.3	12.6
B lymphocytes CD40L and IL-4	15.7	14.2	17.7	13.1	13.2
EOL-1 dbcAMP	0.1	0.7	0.2	0.1	0.2
EOL-1 dbcAMP PMA/ionomycin	0.1	0.2	0.1	0.2	0.1
Dendritic cells none	0.2	0.2	0.1	0.0	0.1
Dendritic cells LPS	0.1	0.0	0.0	0.2	0.0
Dendritic cells anti-CD40	0.0	0.0	0.0	0.0	0.0
Monocytes rest	0.1	0.1	0.0	0.0	0.2
Monocytes LPS	0.3	0.2	0.1	0.2	0.0
Macrophages rest	0.8	0.4	0.0	0.2	0.1
Macrophages LPS	0.0	0.3	0.0	0.1	0.0
HUVEC none	8.3	7.5	7.2	7.3	4.6
HUVEC starved	16.0	18.3	21.5	13.6	16.4
HUVEC IL-1beta	4.0	2.9	4.1	5.2	5.1
HUVEC IFN gamma	12.8	11.7	7.9	13.9	14.2
HUVEC TNF alpha + IFN gamma	1.3	1.0	2.6	1.5	2.7
HUVEC TNF alpha + IL4	8.2	6.5	7.1	7.6	7.6
HUVEC IL-11	8.0	6.9	5.1	7.1	5.9
Lung Microvascular EC none	15.2	13.9	15.2	16.6	14.3
Lung Microvascular EC	5.5	8.4	9.9	7.8	9.0
TNFalpha + IL-1beta
Microvascular Dermal EC none	6.3	5.7	2.8	6.4	1.8
Microsvasular Dermal EC	1.9	1.8	1.0	2.2	0.6
TNFalpha + IL-1beta
Bronchial epithelium	0.2	0.1	0.5	0.4	0.0
TNFalpha + IL1beta
Small airway epithelium none	0.5	0.1	0.4	0.3	0.0
Small airway epithelium	1.0	0.9	1.3	1.6	1.2
TNFalpha + IL-1beta
Coronery artery SMC rest	0.5	0.4	1.0	0.4	1.7
Coronery artery SMC	0.7	0.4	0.3	0.5	0.6
TNFalpha + IL-1beta
Astrocytes rest	3.0	2.1	4.0	2.7	3.8
Astrocytes TNFalpha +	4.2	2.8	3.5	5.4	4.4
IL-1beta
KU-812 (Basophil) rest	3.9	3.0	3.4	4.3	3.6
KU-812 (Basophil) PMA/ionomycin	38.2	46.7	46.3	48.6	58.2
CCD1106 (Keratinocytes) none	0.0	0.0	0.0	0.4	0.1
CCD1106 (Keratinocytes)	0.2	0.0	0.0	0.2	0.0
TNFalpha + IL-1beta
Liver cirrhosis	14.7	13.7	10.1	13.6	12.6
Lupus kidney	4.9	6.2	0.7	5.5	2.6
NCI-H292 none	7.4	9.8	9.1	7.1	8.0
NCI-H292 IL-4	4.2	5.1	5.5	5.5	4.0
NCI-H292 IL-9	7.7	8.1	9.6	9.6	9.2
NCI-H292IL-13	2.6	2.5	1.9	3.6	3.8
NCI-H292 IFN gamma	1.8	2.6	2.6	2.1	2.4
HPAEC none	11.4	9.3	5.3	10.3	7.7
HPAEC TNF alpha +	12.1	10.0	6.3	7.4	9.9
IL-1 beta
Lung fibroblast none	2.0	1.9	1.2	2.7	1.8
Lung fibroblast TNF	0.7	0.7	1.4	0.8	0.6
alpha + IL-1 beta
Lung fibroblast IL-4	2.2	2.4	4.2	0.0	3.3
Lung fibroblast IL-9	2.0	2.6	1.7	2.0	1.6
Lung fibroblast IL-13	6.4	4.7	1.6	7.2	4.2
Lung fibroblast IFN gamma	4.1	5.5	3.6	4.9	3.4
Dermal fibroblast CCD1070	4.9	5.8	5.8	8.0	5.5
rest
Dermal fibroblast CCD1070	10.0	9.4	11.7	9.5	10.6
TNF alpha
Dermal fibroblast CCD1070	2.7	2.6	2.6	3.4	2.0
IL-1 beta
Dermal fibroblast IFN gamma	0.9	2.8	2.2	3.4	3.1
Dermal fibroblast IL-4	16.3	10.7	13.2	14.2	14.9
IBD Colitis 2	1.2	1.7	0.2	1.3	0.9
IBD Crohn's	1.0	1.4	1.4	1.6	1.5
Colon	5.6	4.9	7.7	7.4	10.9
Lung	9.3	12.9	11.8	11.5	14.3
Thymus	31.9	36.1	18.3	31.2	19.9
Kidney	7.0	6.5	6.7	6.5	6.5
Column A - Rel. Exp. (%) Ag168, Run 140051854
Column B - Rel. Exp. (%) Ag168fam, Run 140051832
Column C - Rel. Exp. (%) Ag2823, Run 162350532
Column D - Rel. Exp. (%) Ag33, Run 138624287
Column E - Rel. Exp. (%) Ag33, Run 147205830

[0650]

TABLE DJ
Panel 5 Islet
Tissue Name                      A
97457_Patient-02go_adipose       58.6
97476_Patient-07sk_skeletal muscle 70.7
97477_Patient-07ut_uterus        60.3
97478_Patient-07pl_placenta      14.2
99167_Bayer Patient 1            5.7
97482_Patient-08ut_uterus        28.3
97483_Patient-08pl_placenta      31.2
97486_Patient-09sk_skeletal muscle 7.0
97487_Patient-09ut_uterus        100.0
97488_Patient-09pl_placenta      5.6
97492_Patient-10ut_uterus        78.5
97493_Patient-10pl_placenta      11.3
97495_Patient-11go_adipose       26.2
97496_Patient-11sk_skeletal muscle 4.9
97497_Patient-11ut_uterus        63.3
97498_Patient-11pl_placenta      7.2
97500_Patient-12go_adipose       55.1
97501_Patient-12sk_skeletal muscle 10.4
97502_Patient-12ut_uterus        53.6
97503_Patient-12pl_placenta      7.0
94721_Donor 2 U - A_Mesenchymal Stem Cells 4.8
94722_Donor 2 U - B_Mesenchymal Stem Cells 4.5
94723_Donor 2 U - C_Mesenchymal Stem Cells 14.7
94709_Donor 2 AM - A_adipose     15.0
94710_Donor 2 AM - B_adipose     14.0
94711_Donor 2 AM - C_adipose     5.2
94712_Donor 2 AD - A_adipose     18.9
94713_Donor 2 AD - B_adipose     18.0
94714_Donor 2 AD - C_adipose     20.4
94742_Donor 3 U - A_Mesenchymal Stem Cells 2.0
94743_Donor 3 U - B_Mesenchymal Stem Cells 2.5
94730_Donor 3 AM - A_adipose     4.3
94731_Donor 3 AM - B_adipose     2.8
94732_Donor 3 AM - C_adipose     2.4
94733_Donor 3 AD - A_adipose     2.1
94734_Donor 3 AD - B_adipose     0.6
94735_Donor 3 AD - C_adipose     1.4
77138_Liver_HepG2untreated       1.7
73556_Heart_Cardiac stromal cells (primary) 8.6
81735_Small Intestine            18.2
72409_Kidney_Proximal Convoluted Tubule 1.3
82685_Small intestine_Duodenum   11.0
90650_Adrenal_Adrenocortical adenoma 97.9
72410_Kidney_HRCE                4.6
72411_Kidney_HRE                 6.4
73139_Uterus_Uterine smooth muscle cells 4.2
Column A - Rel. Exp. (%) Ag2823, Run 248195300

[0651] Oncology_cell_line_screening_panel_v3.1 Summary: Ag66 Highest expression seen in T98G glioblastoma cell line (CT=28.5). Moderate to low expression is seen in other brain, pancreatic, lung, and lymphoma cancer cell lines. This gene and/or expressed protein can be used to differentiate these cancer cells from normal cells.

[0652] Panel 1.3D Summary: Ag2823 Highest Expression is seen in a glioma cell line, SF-295 (CT=28.7) with moderate expression OVCAR5 ovarian cancer cell line. Moderate levels of expression are seen in samples from select normal tissues, including adrenal gland, pituitary gland, bladder and pancreas. Low but significant levels of expression are seen in heart, uterus, and adipose.

[0653] Panel 2D Summary: Highest expression is seen in a kidney cancer (CTs=27.5), with prominent expression detected in normal bladder and ovarian cancer, and lower expression levels seen in many of the samples on this panel. A third experiment with a different probe and primer set shows highest expression in prostate cancer (CT=33.5), with low but significant expression in normal lung.

[0654] Panel 4D Summary: Ag168/Ag168fam/Ag2823/Ag33 Highest expression is seen in ionomycin treated Ramos B cells (CTs=28). In addition, the expression is higher in the treated Ramos B cells than in the untreated cells, as well as in ionomycin treated Ku-812 basophils cells when compared to resting Ku-812 cells. Moderate to low levels of expression are seen in LAK cells, B cells treated with the B cell mitogen, PWM, or CD40L and IL-4, HUVECs, HMVECs, lung and dermal microvascular endothelial cells and fibroblasts, and thymus.

[0655] Panel 5 Islet Summary: Ag2823 Highest expression is seen in uterus (CT=31.5), with prominent expression in adrenalcortical adenoma.

E. NOV 5, CG52676-02: T Cell Immunoglobulin Mucin-3

[0656] Expression of gene CG52676-02 was assessed using the primer-probe set Ag3864, described in Table EA. Results of the RTQ-PCR runs are shown in Tables EB, EC, ED and EE.

TABLE EA
Probe Name Ag3864
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-aacctcgtgcccgtctgc-3′	18	725	198
Probe	TET-5′-ctgtcctgtgtttgaatgtggcaacgt-3′-	27	757	199
	TAMRA
Reverse	5′-attcacatccctttcatcag-3′	20	795	200

[0657]

TABLE EB
A1.05 chondrosarcoma
Tissue Name                      A
138353_PMA(18 hrs)               30.6
138352 IL-1 beta + Oncostatin M (18 hrs) 27.0
138351_IL-1beta + TNFa (18 hrs)  23.7
138350_IL-1beta (18 hrs)         14.7
138354 Untreated-complete medium (18 hrs) 10.1
138347_PMA (6 hrs)               100.0
138346 IL-1 beta + Oncostatin M (6 hrs) 36.1
138345_IL-1beta + TNFa (6 hrs)   7.1
138344_IL-1beta (6 hrs)          9.2
138348 Untreated-complete medium (6 hrs) 15.3
138349 Untreated-serum starved (6 hrs) 37.9
Column A - Rel. Exp. (%) Ag3864, Run 312127716

[0658]

TABLE EC
General_screening_panel_v1.4
Tissue Name                      A
Adipose                          22.7
Melanoma* Hs688(A).T             0.2
Melanoma* Hs688(B).T             0.0
Melanoma* M14                    0.0
Melanoma* LOXIMVI                0.3
Melanoma* SK-MEL-5               0.6
Squamous cell carcinoma SCC-4    0.1
Testis Pool                      7.0
Prostate ca.* (bone met) PC-3    0.6
Prostate Pool                    4.0
Placenta                         9.0
Uterus Pool                      1.6
Ovarian ca. OVCAR-3              0.1
Ovarian ca. SK-OV-3              0.7
Ovarian ca. OVCAR-4              0.0
Ovarian ca. OVCAR-5              1.0
Ovarian ca. IGROV-1              0.1
Ovarian ca. OVCAR-8              0.0
Ovary                            8.7
Breast ca. MCF-7                 0.4
Breast ca. MDA-MB-231            0.5
Breast ca. BT 549                1.0
Breast ca. T47D                  1.6
Breast ca. MDA-N                 0.1
Breast Pool                      13.4
Trachea                          15.5
Lung                             2.4
Fetal Lung                       36.6
Lung ca. NCI-N417                0.0
Lung ca. LX-1                    0.7
Lung ca. NCI-H146                0.0
Lung ca. SHP-77                  0.1
Lung ca. A549                    0.2
Lung ca. NCI-H526                0.0
Lung ca. NCI-H23                 1.4
Lung ca. NCI-H460                0.0
Lung ca. HOP-62                  0.2
Lung ca. NCI-H522                0.2
Liver                            5.7
Fetal Liver                      10.7
Liver ca. HepG2                  1.4
Kidney Pool                      15.6
Fetal Kidney                     17.3
Renal ca. 786-0                  5.7
Renal ca. A498                   0.4
Renal ca. ACHN                   0.1
Renal ca. UO-31                  0.8
Renal ca. TK-10                  2.1
Bladder                          87.1
Gastric ca. (liver met.) NCI-N87 1.2
Gastric ca. KATO III             0.2
Colon ca. SW-948                 0.1
Colon ca. SW480                  2.0
Colon ca.* (SW480 met) SW620     0.1
Colon ca. HT29                   0.0
Colon ca. HCT-116                0.1
Colon ca. CaCo-2                 3.6
Colon cancer tissue              68.3
Colon ca. SW1116                 0.0
Golon ca. Colo-205               0.0
Colon ca. SW-48                  0.0
Colon Pool                       17.1
Small Intestine Pool             8.0
Stomach Pool                     9.3
Bone Marrow Pool                 5.6
Fetal Heart                      3.9
Heart Pool                       4.6
Lymph Node Pool                  9.6
Fetal Skeletal Muscle            4.6
Skeletal Muscle Pool             4.7
Spleen Pool                      100.0
Thymus Pool                      23.8
CNS cancer (glio/astro) U87-MG   0.6
CNS cancer (glio/astro) U-118-MG 0.9
CNS cancer (neuro; met) SK-N-AS  0.2
CNS cancer (astro) SF-539        0.8
CNS cancer (astro) SNB-75        3.1
CNS cancer(glio) SNB-19          0.1
CNScancer (glio) SF-295          0.7
Brain (Amygdala) Pool            29.5
Brain (cerebellum)               18.0
Brain (fetal)                    7.6
Brain (Hippocampus) Pool         37.6
Cerebral Cortex Pool             24.0
Brain (Substantia nigra) Pool    27.7
Brain (Thalamus) Pool            43.5
Brain (whole)                    21.6
Spinal Cord Pool                 73.7
Adrenal Gland                    25.7
Pituitary gland Pool             0.8
Salivary Gland                   4.0
Thyroid (female)                 2.7
Pancreatic ca. CAPAN2            0.1
Pancreas Pool                    16.2
Column A - Rel. Exp. (%) Ag3864, Run 217310197

[0659]

TABLE ED
Panel 2.2
Tissue Name                      A
Normal Colon                     4.7
Colon cancer (OD06064)           20.4
Colon Margin (OD06064)           2.5
Colon cancer (OD06159)           1.0
Colon Margin (OD06159)           1.7
Colon cancer (OD06297-04)        1.3
Colon Margin (OD06297-05)        4.9
CC Gr.2 ascend colon (ODO3921)   1.3
CC Margin (ODO3921)              2.3
Colon cancer metastasis (OD06104) 7.3
Lung Margin (OD06104)            20.0
Colon mets to lung (OD04451-01)  20.6
Lung Margin (OD04451-02)         21.6
Normal Prostate                  0.5
Prostate Cancer (OD04410)        0.6
Prostate Margin (OD04410)        0.8
Normal Ovary                     2.4
Ovarian cancer (OD06283-03)      12.9
Ovarian Margin (OD06283-07)      4.7
Ovarian Cancer 064008            3.4
Ovarian cancer (OD06145)         8.3
Ovarian Margin (OD06145)         2.3
Ovarian cancer (OD06455-03)      1.1
Ovarian Margin (OD06455-07)      1.8
Normal Lung                      9.9
Invasive poor diff. lung adeno (ODO4945-01) 10.0
Lung Margin (ODO4945-03)         29.3
Lung Malignant Cancer (OD03126)  7.1
Lung Margin (OD03 126)           7.4
Lung Cancer (OD05014A)           13.1
Lung Margin (OD05014B)           35.4
Lung cancer (OD06081)            3.6
Lung Margin (OD06081)            12.9
Lung Cancer (OD04237-01)         5.9
Lung Margin (OD04237-02)         32. 1
Ocular Melanoma Metastasis       0.4
Ocular Melanoma Margin (Liver)   4.1
Melanoma Metastasis              1.5
Melanoma Margin (Lung)           11.0
Normal Kidney                    3.7
Kidney Ca, Nuclear grade 2 (OD04338) 23.0
Kidney Margin (OD04338)          100.0
Kidney Ca Nuclear grade 1/2 (OD04339) 24.5
Kidney Margin (OD04339)          16.0
Kidney Ca, Clear cell type (OD04340) 4.9
Kidney Margin (OD04340)          6.8
Kidney Ca, Nuclear grade 3 (OD04348) 3.4
Kidney Margin (OD04348)          31.2
Kidney malignant cancer (OD06204B) 0.7
Kidney normal adjacent tissue (OD06204E) 18.7
Kidney Cancer (OD04450-01)       17.0
Kidney Margin (OD04450-03)       11.1
Kidney Cancer 8120613            0.0
Kidney Margin 8120614            25.9
Kidney Cancer 9010320            9.6
Kidney Margin 9010321            18.8
Kidney Cancer 8120607            5.3
Kidney Margin 8120608            19.9
Normal Uterus                    2.8
Uterine Cancer 064011            3.7
Normal Thyroid                   0.2
Thyroid Cancer 064010            2.0
Thyroid Cancer A302152           5.0
Thyroid Margin A302153           1.2
Normal Breast                    4.3
Breast Cancer (OD04566)          4.0
Breast Cancer 1024               3.9
Breast Cancer (OD04590-01)       10.6
Breast Cancer Mets (OD04590-03)  14.5
Breast Cancer Metastasis (OD04655-05) 6.1
Breast Cancer 064006             8.2
Breast Cancer 9100266            2.4
Breast Margin 9100265            2.4
Breast Cancer A209073            0.5
Breast Margin A2090734           2.2
Breast cancer (OD06083)          13.8
Breast cancer node metastasis (OD06083) 16.0
Normal Liver                     3.1
Liver Cancer 1026                2.5
Liver Cancer 1025                10.6
Liver Cancer 6004-T              4.5
Liver Tissue 6004-N              1.2
Liver Cancer 6005-T              8.1
Liver Tissue 6005-N              20.7
Liver Cancer 064003              2.4
Normal Bladder                   7.3
Bladder Cancer 1023              2.5
Bladder Cancer A302173           6.0
Normal Stomach                   5.2
Gastric Cancer 9060397           4.1
Stomach Margin 9060396           5.5
Gastric Cancer 9060395           5.6
Stomach Margin 9060394           9.6
Gastric Cancer 064005            2.6
Column A - Rel. Exp. (%) Ag3864, Run 174448455

[0660]

TABLE EE
Panel 4.1D
Tissue Name                      A
Secondary Th1 act                100.0
Secondary Th2 act                39.0
Secondary Tr1 act                36.6
Secondary Th1 rest               14.0
Secondary Th2 rest               3.3
Secondary Tr1 rest               4.9
Primary Th1 act                  8.3
Primary Th2 act                  4.8
Primary Tr1 act                  7.1
Primary Th1 rest                 5.5
Primary Th2 rest                 3.6
Primary Tr1 rest                 2.9
CD45RA CD4 lymphocyte act        7.6
CD45RO CD4 lymphocyte act        12.8
CDS lymphocyte act               6.5
Secondary CDS lymphocyte rest    10.4
Secondary CDS lymphocyte act     11.4
CD4 lymphocyte none              0.5
2ry Th1/Th2/Tr1_anti-CD95 CH11   6.7
LAK cells rest                   17.7
LAK cells IL-2                   31.0
LAK cells IL-2 + IL-12           35.4
LAK cells IL-2 + IFN gamma       12.6
LAK cells IL-2 + IL-18           15.7
LAK cells PMA/ionomycin          24.1
NK Cells IL-2 rest               24.7
Two Way MLR 3 day                11.2
Two Way MLR 5 day                13.3
Two Way MLR 7 day                15.8
PBMC rest                        1.7
PBMC PWM                         15.4
PBMC PHA-L                       7.6
Ramos (B cell) none              0.0
Ramos (B cell) ionomycin         0.3
B lymphocytes PWM                5.4
B lymphocytes CD40L and IL-4     0.3
EOL-1 dbcAMP                     0.1
EOL-1 dbcAMP PMA/ionomycin       2.8
Dendritic cells none             25.0
Dendritic cells LPS              13.7
Dendritic cells anti-CD40        29.5
Monocytes rest                   4.9
Monocytes LPS                    7.2
Macrophages rest                 41.5
Macrophages LPS                  8.8
HUVEC none                       0.0
HUVEC starved                    0.0
HUVEC IL-1beta                   0.0
HUVEC IFN gamma                  0.1
HUVEC TNF alpha + IFN gamma      0.0
HUVEC TNF alpha + IL4            0.0
HUVEC IL-11                      0.0
Lung Microvascular EC none       0.0
Lung Microvascular EC TNFalpha + IL-1beta 0.0
Microvascular Dermal EC none     0.0
Microsvasular Dermal EC TNFalpha + IL-1beta 0.0
Bronchial epithelium TNFalpha + IL1beta 0.0
Small airway epithelium none     0.0
Small airway epithelium TNFalpha + IL-1beta 0.0
Coronery artery SMC rest         0.0
Coronery artery SMC TNFalpha + IL-1beta 0.0
Astrocytes rest                  0.0
Astrocytes TNFalpha + IL-1beta   0.0
KU-812 (Basophil) rest           0.1
KU-812 (Basophil) PMA/ionomycin  0.7
CCD1 106 (Keratinocytes) none    0.0
CCD1 106 (Keratinocytes) TNFalpha + IL-1beta 0.0
Liver cirrhosis                  1.3
NCI-H292 none                    0.0
NCI-H292 IL-4                    0.0
NCI-H292 IL-9                    0.0
NCI-H292IL-13                    0.0
NCI-H292 IFN gamma               0.0
HPAEC none                       0.0
HPAEC TNF alpha + IL-1 beta      0.0
Lung fibroblast none             0.1
Lung fibroblast TNF alpha + IL-1 beta 0.4
Lung fibroblast IL-4             0.1
Lung fibroblast IL-9             0.3
Lung fibroblast IL-13            0.1
Lung fibroblast IFN gamma        0.5
Dermal fibroblast CCD1070 rest   0.6
Dermal fibroblast CCD1070 TNF alpha 16.0
Dermal fibroblast CCD1070 IL-1 beta 0.0
Dermal fibroblast IFN gamma      0.0
Dermal fibroblast IL-4           0.0
Dermal Fibroblasts rest          0.0
Neutrophils TNFa + LPS           0.3
Neutrophils rest                 0.0
Colon                            0.3
Lung                             3.5
Thymus                           1.6
Kidney                           2.8
Column A - Rel. Exp. (%) Ag3864, Run 172209244

[0661] AI.05 chondrosarcoma Summary: Ag3864 Highest expression of this gene is seen in PMA treated chondrosarcoma cell line (SW1353)(CT=31.4). This gene shows expression in cells treated with cytokines. Cytokines such as IL-1 beta are potent activators of pro-inflammatory cytokines and matrix metalloproteinases which participate in the destruction of cartilage observed in Osteoarthritis (OA). Thus, modulation of the expression of this gene or its protein product in chondrocytes by for example, antibodies, small molecules or antisense will be important for preventing the degeneration of cartilage observed in OA.

[0662] General_screening_panel_v1.4 Summary: Ag3864 Highest expression of this gene is detected in spleen (CT=28.4). Expression of this gene is higher in fetal lung (CTs=28.9) than in adult lung tissue (CTs=33). Thus, this gene may play a role in early development of these tissue. Therefore, therapeutic modulation of this gene or its protein product will be useful in the treatment of diseases related to development of these tissues. Low, but significant expression of this gene is seen in colon, breast, renal and CNS cancer cell lines on this panel and modulation of expression will be used for treatment of these cancers.

[0663] Among tissues with metabolic function, this gene is expressed at low levels in adipose, adult and fetal liver, adult and fetal heart, adult and fetal skeletal muscle, adrenal, thyroid and pancreas. Based on its tissue distribution, this gene product will be important for the pathogenesis, diagnosis, and/or treatment of endocrine and metabolic disease, including obesity and Types 1 and 2 diabetes.

[0664] This gene is expressed at moderate levels in the CNS. Therapeutic modulation of this gene or its protein product will be of use in controlling the inflammatory response and be of benefit in any clinical condition associated with neuroinflammation, such as stroke, head or spinal cord trauma, multiple sclerosis, Alzheimer's disease, and viral infections of the CNS.

[0665] Panel 2.2 Summary: Ag3864 This gene is generally expressed at low levels in the tissues in panel 2.2. The highest expression is seen in a normal kidney sample (CT=29.7).

[0666] Increased expression is seen in 5 of 6 normal lung tissues compared to lung cancer and in 7 of 9 normal kidney tissues compared to the adjacent cancer tissue. Thus, loss of expression of this gene will be associated with these cancers and therapeutic modulation of this gene will therefore be of use in the treatment of these cancers.

[0667] Panel 4.1D Summary: Ag 3864 This gene is expressed in T cells, particularly chronically activated Th1, Th2 and Tr1 cells but also LAK cells, macrophages and dendritic cells. The only non-hematopoietic cell type that expresses this gene are dermal fibroblasts. Lung, thymus and kidney also express low levels of the transcript. Thus, this transcript or the protein it encodes could be used to detect hematopoietically-derived cells. Furthermore, therapeutics designed with the protein encoded by this transcript could be important in the regulation the function of antigen presenting cells (macrophages and dendritic cells)or T cells and be important in the treatment of asthma, emphysema, psoriasis, arthrtis, and IBD.

F. NOV 6, CG52997-01: LRR Containing Protein

[0668] Expression of gene CG52997-01 was assessed using the primer-probe sets Ag1094, Ag273b, Ag6719 and Ag6725, described in Tables FA, FB, FC and FD. Results of the RTQ-PCR runs are shown in Tables FE, FF, FG, FH, FI, FJ, FK, FL and FM.

TABLE FA
Probe Name Ag1094
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-atggactggaaaacctggaa-3′	20	581	201
Probe	TET-5′-tcctgcaagcagataacaattttatcaca-3′-	29	602	202
	TAMRA
Reverse	5′-tgctaaaggcacttggttca-3′	20	636	203

[0669]

TABLE FB
Probe Name Ag273b
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-cggcttgacgatgcttcac-3′	19	405	204
Probe	TET-5′-tgacttttctgggcttaccaatgctatttcaa-	32	429	205
	3′-TAMRA
Reverse	5′-gcacctatctcaatatctgcaatattg-3′	27	477	206

[0670]

TABLE FC
Probe Name Ag6719
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-ggaaaatcattcaccactcaca-3′	22	2355	207
Probe	TET-5′-acaaaaccacgaaccaatcaacagaa-3′-	26	2393	208
	TAMRA
Reverse	5′-tctgtacaatgagctggcatct-3′	22	2433	209

[0671]

TABLE FD
Probe Name Ag6725
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gaagctgtggattcatctctttt-3′	23	186	210
Probe	TET-5′-catctctccttgcctgtatatctttacactcc-	32	212	211
	3′-TAMRA
Reverse	5′-ggatgagagcactggagtttg-3′	21	244	212

[0672]

TABLE FE
Ardais Panel v.1.0
Tissue Name             A
136799_Lung cancer(362) 0.1
136800_Lung NAT(363)    4.8
136813_Lung cancer(372) 37.4
136814_Lung NAT(373)    2.8
136815_Lung cancer(374) 19.9
136816_Lung NAT(375)    4.3
136791_Lung cancer(35A) 0.5
136795_Lung cancer(35E) 100.0
136797_Lung cancer(360) 0.2
136794_lung NAT(35D)    5.0
136818_Lung NAT(377)    5.4
136787_lung cancer(356) 0.2
136788_lung NAT(357)    0.7
136804_Lung cancer(369) 1.1
136805_Lung NAT(36A)    2.5
136806_Lung cancer(36B) 18.2
136807_Lung NAT(36C)    2.4
136789_lung cancer(358) 0.7
136802_Lung cancer(365) 0.1
136803_Lung cancer(368) 1.1
136811_Lung cancer(370) 4.5
136810_Lung NAT(36F)    32.1
Column A - Rel. Exp. (%) Ag1094, Run 263147830

[0673]

TABLE FF
General_screening_panel_v1.6
Tissue Name                      A
Adipose                          0.7
Melanoma* Hs688(A).T             0.0
Melanoma* Hs688(B).T             0.0
Melanoma* M14                    0.0
Melanoma* LOXIMVI                0.0
Melanoma* SK-MEL-5               0.6
Squamous cell carcinoma SCC-4    7.4
Testis Pool                      0.5
Prostate ca.* (bone met) PC-3    28.1
Prostate Pool                    6.2
Placenta                         0.0
Uterus Pool                      0.3
Ovarian ca. OVCAR-3              0.4
Ovarian ca. SK-OV-3              0.4
Ovarian ca. OVCAR-4              0.0
Ovarian ca. OVCAR-5              10.3
Ovarian ca. IGROV-1              10.2
Ovarian ca. OVCAR-8              1.0
Ovary                            0.0
Breast ca. MCF-7                 0.8
Breast ca. MDA-MB-231            0.0
Breast ca. BT 549                0.9
Breast ca. T47D                  0.0
Breast ca. MDA-N                 0.0
Breast Pool                      1.2
Trachea                          4.6
Lung                             0.0
Fetal Lung                       14.4
Lung ca. NCI-N417                0.0
Lung ca. LX-1                    0.0
Lung ca. NCI-H146                16.8
Lung ca. SHP-77                  100.0
Lung ca. A549                    2.7
Lung ca. NCI-H526                0.0
Lung ca. NCI-H23                 12.9
Lung ca. NCI-H460                0.0
Lung ca. HOP-62                  3.2
Lung ca. NCI-H522                0.1
Liver                            0.0
Fetal Liver                      2.7
Liver ca. HepG2                  0.0
Kidney Pool                      0.4
Fetal Kidney                     7.8
Renal ca. 786-0                  0.0
Renal ca. A498                   0.5
Renal ca. ACHN                   0.0
Renal ca. UO-31                  0.0
Renal ca. TK-10                  0.0
Bladder                          0.1
Gastric ca. (liver met.) NCI-N87 9.5
Gastric ca. KATO III             9.5
Colon ca. SW-948                 1.0
Colon ca. SW480                  0.0
Colon ca.* (SW480 met) SW620     0.4
Colon ca. HT29                   15.5
Colon ca. HCT-116                0.0
Colon ca. CaCo-2                 0.0
Colon cancer tissue              0.0
Colon ca. SW1116                 0.0
Colon ca. Colo-205               0.0
Colon ca. SW-48                  0.0
Colon Pool                       1.0
Small Intestine Pool             0.9
Stomach Pool                     1.1
Bone Marrow Pool                 0.6
Fetal Heart                      0.9
Heart Pool                       0.2
Lymph Node Pool                  0.5
Fetal Skeletal Muscle            0.6
Skeletal Muscle Pool             0.0
Spleen Pool                      0.0
Thymus Pool                      1.5
CNS cancer (glio/astro) U87-MG   0.2
CNS cancer (glio/astro) U-118-MG 0.7
CNS cancer (neuro; met) SK-N-AS  18.0
CNS cancer (astro) SF-539        0.0
CNS cancer (astro) SNB-75        6.3
CNS cancer (glio) SNB-19         7.4
CNS cancer (glio) SF-295         68.3
Brain (Amygdala) Pool            0.6
Brain (cerebellum)               0.2
Brain (fetal)                    0.7
Brain (Hippocampus) Pool         0.3
Cerebral Cortex Pool             0.1
Brain (Substantia nigra) Pool    0.1
Brain (Thalamus) Pool            0.8
Brain (whole)                    0.1
Spinal Cord Pool                 0.3
Adrenal Gland                    0.0
Pituitary gland Pool             0.0
Salivary Gland                   0.5
Thyroid (female)                 0.0
Pancreatic ca. CAPAN2            0.0
Pancreas Pool                    0.0
Column A - Rel. Exp. (%) Ag6719, Run 277223815

[0674]

TABLE FG
Panel 1
Tissue Name                      A
Endothelial cells                0.0
Endothelial cells (treated)      0.0
Pancreas                         0.0
Pancreatic ca. CAPAN 2           0.0
Adrenal gland                    0.0
Thyroid                          0.0
Salivary gland                   12.9
Pituitary gland                  0.1
Brain (fetal)                    0.0
Brain (whole)                    0.2
Brain (amygdala)                 0.0
Brain (cerebellum)               1.6
Brain (hippocampus)              0.0
Brain (substantia nigra)         0.0
Brain (thalamus)                 2.9
Brain (hypothalamus)             0.1
Spinal cord                      0.0
glio/astro U87-MG                0.0
glio/astro U-118-MG              0.0
astrocytoma SW1783               0.1
neuro*; met SK-N-AS              6.6
astrocytoma SF-539               0.0
astrocytoma SNB-75               10.2
glioma SNB-19                    24.3
glioma U251                      4.2
glioma SF-295                    37.6
Heart                            1.5
Skeletal muscle                  0.0
Bone marrow                      0.0
Thymus                           0.4
Spleen                           0.0
Lymph node                       0.0
Colon (ascending)                9.9
Stomach                          0.4
Small intestine                  4.2
Colon ca. SW480                  0.0
Colon ca.* SW620 (SW480 met)     0.0
Colon ca. HT29                   34.4
Colon ca. HCT-116                0.0
Colon ca. CaCo-2                 0.0
Colon ca. HCT-15                 0.0
Colon ca. HCC-2998               0.0
Gastric ca. * (liver met) NCI-N87 1.3
Bladder                          0.1
Trachea                          8.9
Kidney                           0.2
Kidney (fetal)                   1.3
Renal ca. 786-0                  0.0
Renal ca. A498                   0.0
Renal ca. RXF 393                0.0
Renal ca. ACHN                   0.0
Renal ca. UO-31                  0.0
Renal ca. TK-10                  0.0
Liver                            0.0
Liver (fetal)                    0.0
Liver ca. (hepatoblast) HepG2    0.0
Lung                             0.5
Lung (fetal)                     2.2
Lung ca. (small cell) LX-1       0.0
Lung ca. (small cell) NCI-H69    2.7
Lung ca. (s. cell var.) SHP-77   44.1
Lung ca. (large cell)NCI-H460    0.0
Lung ca. (non-sm. cell) A549     0.0
Lung ca. (non-s. cell) NCI-H23   14.7
Lung ca. (non-s. cell) HOP-62    12.2
Lung ca. (non-s. cl) NCI-H522    0.2
Lung ca. (squam.) SW 900         11.9
Lung ca. (squam.) NCI-H596       2.5
Mammary gland                    4.8
Breast ca.* (pl. ef) MCF-7       0.4
Breast ca.* (pl. ef) MDA-MB-231  0.0
Breast ca.* (pl. ef) T47D        7.2
Breast ca. BT-549                0.0
Breast ca. MDA-N                 0.0
Ovary                            0.0
Ovarian ca. OVCAR-3              0.0
Ovarian ca. OVCAR-4              0.0
Ovarian ca. OVCAR-5              6.2
Ovarian ca. OVCAR-8              0.1
Ovarian ca. IGROV-1              0.0
Ovarian ca. (ascites) SK-OV-3    0.0
Uterus                           0.0
Placenta                         0.8
Prostate                         3.6
Prostate ca.* (bone met) PC-3    100.0
Testis                           0.0
Melanoma Hs688(A).T              0.0
Melanoma* (met) Hs688(B).T       0.0
Melanoma UACC-62                 0.3
Melanoma M14                     0.0
Melanoma LOX IMVI                0.0
Melanoma* (met) SK-MEL-5         0.0
Melanoma SK-MEL-28               0.2
Column A - Rel. Exp. (%) Ag273b, Run 109655993

[0675]

TABLE FH
Panel 1.3D
	Tissue Name	A	B
	Liver adenocarcinoma	10.0	9.1
	Pancreas	0.2	0.1
	Pancreatic ca. CAPAN 2	0.0	0.0
	Adrenal gland	0.1	0.1
	Thyroid	0.2	0.2
	Salivary gland	8.9	4.3
	Pituitary gland	0.1	0.2
	Brain (fetal)	0.1	0.1
	Brain (whole)	0.8	0.6
	Brain (amygdala)	0.2	0.1
	Brain (cerebellum)	0.5	0.7
	Brain (hippocampus)	0.4	0.2
	Brain (substantia nigra)	0.0	0.1
	Brain (thalamus)	1.1	1.0
	Cerebral Cortex	0.2	0.1
	Spinal cord	0.2	0.1
	glio/astro U87-MG	0.1	0.2
	glio/astro U-118-MG	1.0	0.8
	astrocytoma SW1783	1.1	0.9
	neuro*; met SK-N-AS	26.4	26.8
	astrocytoma SF-539	0.0	0.0
	astrocytoma SNB-75	15.1	12.9
	glioma SNB-19	38.2	21.0
	glioma U251	3.3	3.7
	glioma SF-295	38.4	36.9
	Heart (fetal)	0.2	0.5
	Heart	0.6	0.3
	Skeletal muscle (fetal)	2.9	2.2
	Skeletal muscle	0.0	0.0
	Bone marrow	0.0	0.2
	Thymus	0.4	0.1
	Spleen	0.0	0.1
	Lymph node	0.1	0.0
	Colorectal	1.6	0.6
	Stomach	1.6	1.6
	Small intestine	4.2	3.7
	Colon ca. SW480	0.1	0.0
	Colon ca.* SW620(SW480 met)	0.4	0.1
	Colon ca. HT29	21.0	25.5
	Colon ca. HCT-116	0.0	0.0
	Colon ca. CaCo-2	0.1	0.0
	Colon ca. tissue(ODO3866)	0.0	0.1
	Colon ca. HCC-2998	0.0	0.0
	Gastric ca.* (liver met) NCI-N87	21.3	20.7
	Bladder	0.1	0.1
	Trachea	12.5	12.9
	Kidney	0.1	0.0
	Kidney (fetal)	0.9	0.6
	Renal ca. 786-0	0.0	0.0
	Renal ca. A498	2.0	1.5
	Renal ca. RXF 393	0.0	0.0
	Renal ca. ACHN	0.1	0.0
	Renal ca. UO-31	0.0	0.0
	Renal ca. TK-10	0.0	0.0
	Liver	0.4	0.6
	Liver (fetal)	1.6	1.0
	Liver ca. (hepatoblast) HepG2	0.0	0.0
	Lung	1.8	1.4
	Lung (fetal)	11.7	7.5
	Lung ca. (small cell) LX-1	0.2	0.0
	Lung ca. (small cell) NCI-H69	2.4	3.1
	Lung ca. (s. cell var.) SHP-77	100.0	100.0
	Lung ca. (large cell)NCI-H460	0.0	0.0
	Lung ca. (non-sm. cell) A549	0.3	0.8
	Lung ca. (non-s. cell) NCI-H23	12.8	12.8
	Lung ca. (non-s. cell) HOP-62	3.9	3.7
	Lung ca. (non-s. cl) NCI-H522	0.1	0.1
	Lung ca. (squam.) SW 900	4.8	6.4
	Lung ca. (squam.) NCI-H596	1.3	0.9
	Mammary gland	3.4	3.3
	Breast ca.* (pl. ef) MCF-7	1.2	0.7
	Breast ca.* (pl. ef) MDA-MB-231	0.0	0.0
	Breast ca.* (pl. ef) T47D	3.2	3.0
	Breast ca. BT-549	2.1	1.7
	Breast ca. MDA-N	0.0	0.0
	Ovary	0.7	0.3
	Ovarian ca. OVCAR-3	0.4	0.3
	Ovarian ca. OVCAR-4	0.1	0.0
	Ovarian ca. OVCAR-5	8.5	6.3
	Ovarian ca. OVCAR-8	0.0	0.0
	Ovarian ca. IGROV-1	0.0	0.0
	Ovarian ca.* (ascites) SK-OV-3	0.3	0.2
	Uterus	0.4	0.2
	Placenta	1.0	1.3
	Prostate	1.1	1.1
	Prostate ca.* (bone met)PC-3	13.2	13.9
	Testis	0.3	0.4
	Melanoma Hs688(A).T	0.0	0.1
	Melanoma* (met) Hs688(B).T	0.0	0.1
	Melanoma UACC-62	0.0	0.1
	Melanoma M14	0.0	0.0
	Melanoma LOX IMVI	0.0	0.0
	Melanoma* (met) SK-MEL-5	0.1	0.5
	Adipose	0.5	0.4
	Column A - Rel. Exp. (%) Ag1094, Run 147336301
	Column B - Rel. Exp. (%) Ag1094, Run 148015656

[0676]

TABLE FI
Panel 2D
	Tissue Name	A	B
	Normal Colon	12.4	11.4
	CC Well to Mod Diff (ODO3866)	0.1	0.0
	CC Margin (ODO3866)	1.0	1.5
	CC Gr.2 rectosigmoid (ODO3868)	0.3	0.1
	CC Margin (ODO3868)	0.4	0.2
	CC Mod Diff (ODO3920)	0.1	0.1
	CC Margin (ODO3920)	0.8	0.8
	CC Gr.2 ascend colon (ODO3921)	2.4	2.2
	CC Margin (ODO3921)	2.0	1.9
	CC from Partial Hepatectomy	0.0	0.0
	(ODO4309) Mets
	Liver Margin (ODO4309)	0.2	0.3
	Colon mets to lung (OD04451-01)	0.1	0.1
	Lung Margin (OD04451-02)	0.9	0.6
	Normal Prostate 6546-1	2.7	3.0
	Prostate Cancer (OD04410)	1.5	1.4
	Prostate Margin (OD04410)	6.5	8.0
	Prostate Cancer (OD04720-01)	5.9	6.1
	Prostate Margin (OD04720-02)	14.1	12.6
	Normal Lung 061010	3.3	3.5
	Lung Met to Muscle (ODO4286)	0.2	0.2
	Muscle Margin (ODO4286)	0.0	0.0
	Lung Malignant Cancer (OD03126)	7.9	6.0
	Lung Margin (OD03126)	1.8	2.5
	Lung Cancer (OD04404)	24.8	21.6
	Lung Margin (OD04404)	1.8	1.7
	Lung Cancer (OD04565)	0.7	1.2
	Lung Margin (OD04565)	0.5	0.7
	Lung Cancer (OD04237-01)	13.5	12.5
	Lung Margin (OD04237-02)	1.4	1.0
	Ocular Mel Met to Liver (ODO4310)	0.0	0.0
	Liver Margin (ODO4310)	0.2	0.4
	Melanoma Mets to Lung (OD04321)	0.4	0.2
	Lung Margin (OD04321)	2.5	1.2
	Normal Kidney	0.2	0.1
	Kidney Ca, Nuclear grade 2 (OD04338)	0.0	0.0
	Kidney Margin (OD04338)	0.2	0.2
	Kidney Ca Nuclear grade 1/2 (OD04339)	0.0	0.0
	Kidney Margin (OD04339)	0.1	0.0
	Kidney Ca, Clear cell type (OD04340)	0.1	0.2
	Kidney Margin (OD04340)	0.1	0.2
	Kidney Ca, Nuclear grade 3 (OD04348)	0.0	0.0
	Kidney Margin (OD04348)	0.0	0.1
	Kidney Cancer (OD04622-01)	0.4	0.4
	Kidney Margin (OD04622-03)	0.0	0.0
	Kidney Cancer (OD04450-01)	0.0	0.0
	Kidney Margin (OD04450-03)	0.0	0.1
	Kidney Cancer 8120607	0.4	0.3
	Kidney Margin 8120608	0.0	0.0
	Kidney Cancer 8120613	0.0	0.0
	Kidney Margin 8120614	0.0	0.0
	Kidney Cancer 9010320	0.1	0.0
	Kidney Margin 9010321	0.0	0.0
	Normal Uterus	0.1	0.0
	Uterus Cancer 064011	0.5	0.6
	Normal Thyroid	0.5	0.4
	Thyroid Cancer 064010	0.0	0.1
	Thyroid Cancer A302152	0.1	0.1
	Thyroid Margin A302153	0.2	0.1
	Normal Breast	5.5	5.6
	Breast Cancer (OD04566)	0.5	0.7
	Breast Cancer (OD04590-01)	3.0	3.9
	Breast Cancer Mets (OD04590-03)	1.4	1.7
	Breast Cancer Metastasis (OD04655-05)	100.0	100.0
	Breast Cancer 064006	1.7	2.0
	Breast Cancer 1024	0.8	0.8
	Breast Cancer 9100266	3.5	4.1
	Breast Margin 9100265	3.5	4.2
	Breast Cancer A209073	0.7	0.7
	Breast Margin A209073	1.1	1.3
	Normal Liver	2.0	1.7
	Liver Cancer 064003	0.0	0.1
	Liver Cancer 1025	0.3	0.3
	Liver Cancer 1026	0.0	0.0
	Liver Cancer 6004-T	0.3	0.1
	Liver Tissue 6004-N	0.0	0.1
	Liver Cancer 6005-T	0.0	0.0
	Liver Tissue 6005-N	0.1	0.1
	Normal Bladder	0.2	0.1
	Bladder Cancer 1023	3.0	3.1
	Bladder Cancer A302173	1.0	0.8
	Bladder Cancer (OD04718-01)	0.0	0.1
	Bladder Normal Adjacent (OD04718-03)	4.1	3.4
	Normal Ovary	0.1	0.0
	Ovarian Cancer 064008	1.6	1.4
	Ovarian Cancer (OD04768-07)	0.0	0.0
	Ovary Margin (OD04768-08)	0.1	0.0
	Normal Stomach	1.0	1.7
	Gastric Cancer 9060358	0.2	0.2
	Stomach Margin 9060359	0.1	0.2
	Gastric Cancer 9060395	0.4	0.7
	Stomach Margin 9060394	0.4	0.4
	Gastric Cancer 9060397	0.1	0.3
	Stomach Margin 9060396	0.1	0.2
	Gastric Cancer 064005	1.0	1.3
	Column A - Rel. Exp. (%) Ag1094, Run 148015599
	Column B - Rel. Exp. (%) Ag1094, Run 148572893

[0677]

TABLE FJ
Panel 3D
Tissue Name                      A
Daoy- Medulloblastoma            0.0
TE671- Medulloblastoma           0.2
D283 Med- Medulloblastoma        0.2
PFSK-1- Primitive Neuroectodermal 1.6
XF-498- CNS                      30.4
SNB-78- Glioma                   0.7
SF-268- Glioblastoma             0.0
T98G- Glioblastoma               3.3
SK-N-SH- Neuroblastoma (metastasis) 22.4
SF-295- Glioblastoma             27.2
Cerebellum                       6.7
Cerebellum                       0.0
NCI-H292- Mucoepidermoid lung carcinoma 21.9
DMS-114- Small cell lung cancer  2.4
DMS-79- Small cell lung cancer   0.0
NCI-H146- Small cell lung cancer 100.0
NCI-H526- Small cell lung cancer 0.0
NCI-N417- Small cell lung cancer 0.0
NCI-H82- Small cell lung cancer  0.3
NCI-H157- Squamous cell lung cancer (metastasis) 0.0
NCI-H1155- Large cell lung cancer 65.1
NCI-H1299- Large cell lung cancer 0.0
NCI-H727- Lung carcinoid         13.8
NCI-UMC-11- Lung carcinoid       28.7
LX-1- Small cell lung cancer     0.7
Colo-205- Colon cancer           0.0
KM12- Colon cancer               0.1
KM20L2- Colon cancer             7.3
NCI-H716- Colon cancer           80.1
SW-48- Colon adenocarcinoma      0.3
SW1116- Colon adenocarcinoma     0.0
LS 174T- Colon adenocarcinoma    0.0
SW-948- Colon adenocarcinoma     0.6
SW-480- Colon adenocarcinoma     0.0
NCI-SNU-5- Gastric carcinoma     0.0
KATO III- Gastric carcinoma      0.0
NCI-SNU-16- Gastric carcinoma    1.7
NCI-SNU-1- Gastric carcinoma     0.0
RF-1- Gastric adenocarcinoma     0.0
RF-48- Gastric adenocarcinoma    0.0
MKN-45- Gastric carcinoma        0.1
NCI-N87- Gastric carcinoma       2.4
OVCAR-5- Ovarian carcinoma       0.0
RL95-2- Uterine carcinoma        2.8
HelaS3- Cervical adenocarcinoma  0.2
Ca Ski- Cervical epidermoid carcinoma (metastasis) 0.1
ES-2- Ovarian clear cell carcinoma 0.0
Ramos- Stimulated with PMA/ionomycin 6 h 0.1
Ramos- Stimulated with PMA/ionomycin 14 h 0.0
MEG-01- Chronic myelogenous leukemia 1.7
(megokaryoblast)
Raji- Burkitt's lymphoma         0.0
Daudi- Burkitt's lymphoma        0.0
U266- B-cell plasmacytoma        0.2
CA46- Burkitt's lymphoma         0.0
RL- non-Hodgkin's B-cell lymphoma 0.1
JM1- pre-B-cell lymphoma         0.0
Jurkat- T cell leukemia          0.0
TF-1- Erythroleukemia            2.1
HUT 78- T-cell lymphoma          0.0
U937- Histiocytic lymphoma       0.0
KU-812- Myelogenous leukemia     8.2
769-P- Clear cell renal carcinoma 0.0
Caki-2- Clear cell renal carcinoma 0.3
SW 839- Clear cell renal carcinoma 0.0
Rhabdoid kidney tumor            0.0
Hs766T- Pancreatic carcinoma (LN metastasis) 4.9
CAPAN-1- Pancreatic adenocarcinoma 0.3
(liver metastasis)
SU86.86- Pancreatic carcinoma (liver metastasis) 1.5
BxPC-3- Pancreatic adenocarcinoma 23.7
HPAC- Pancreatic adenocarcinoma  76.8
MIA PaCa-2- Pancreatic carcinoma 0.5
CFPAC-1- Pancreatic ductal adenocarcinoma 0.5
PANC-1- Pancreatic epithelioid ductal carcinoma 6.9
T24- Bladder carcinma (transitional cell) 4.1
5637- Bladder carcinoma          1.0
HT-1197- Bladder carcinoma       2.4
UM-UC-3- Bladder carcinma (transitional cell) 0.0
A204- Rhabdomyosarcoma           0.3
HT-1080- Fibrosarcoma            0.2
MG-63- Osteosarcoma              0.2
SK-LMS-1- Leiomyosarcoma (vulva) 0.0
SJRH30- Rhabdomyosarcoma (met to bone marrow) 0.2
A431- Epidermoid carcinoma       0.0
WM266-4- Melanoma                0.4
DU 145- Prostate carcinoma (brain metastasis) 0.0
MDA-MB-468- Breast adenocarcinoma 1.3
SCC-4- Squamous cell carcinoma of tongue 0.2
SCC-9- Squamous cell carcinoma of tongue 0.0
SCC-15- Squamous cell carcinoma of tongue 0.3
CAL 27- Squamous cell carcinoma of tongue 1.6
Column A - Rel. Exp. (%) Ag1094, Run 165022642

[0678]

TABLE FK
Panel 4.1D
Tissue Name	A	B
Secondary Th1 act	0.0	0.0
Secondary Th2 act	0.0	0.0
Secondary Tr1 act	0.0	0.0
Secondary Th1 rest	0.0	0.0
Secondary Th2 rest	0.0	0.0
Secondary Tr1 rest	0.0	0.0
Primary Th1 act	0.0	0.0
Primary Th2 act	0.0	0.0
Primary Tr1 act	0.0	0.0
Primary Th1 rest	0.0	0.0
Primary Th2 rest	0.0	0.0
Primary Tr1 rest	0.0	0.0
CD45RA CD4 lymphocyte act	0.0	0.0
CD45RO CD4 lymphocyte act	0.0	0.0
CD8 lymphocyte act	0.0	0.0
Secondary CD8 lymphocyte rest	0.0	0.0
Secondary CD8 lymphocyte act	0.0	0.0
CD4 lymphocyte none	0.0	0.0
2ry Th1/Th2/Tr1_anti-CD95 CH11	0.0	0.0
LAK cells rest	0.0	0.0
LAK cells IL-2	0.0	0.0
LAK cells IL-2 + IL-12	0.0	0.0
LAK cells IL-2 + IFN gamma	0.0	0.0
LAK cells IL-2 + IL-18	0.0	0.0
LAK cells PMA/ionomycin	0.0	0.0
NK Cells IL-2 rest	0.0	0.0
Two Way MLR 3 day	0.8	0.0
Two Way MLR 5 day	0.0	0.0
Two Way MLR 7 day	0.0	0.0
PBMC rest	0.0	0.0
PBMC PWM	0.0	0.0
PBMC PHA-L	0.0	0.0
Ramos (B cell) none	0.0	0.0
Ramos (B cell) ionomycin	0.6	0.5
B lymphocytes PWM	0.0	0.0
B lymphocytes CD40L and IL-4	0.0	0.0
EOL-1 dbcAMP	0.0	0.0
EOL-1 dbcAMP PMA/ionomycin	0.0	0.0
Dendritic cells none	0.0	0.0
Dendritic cells LPS	0.0	0.0
Dendritic cells anti-CD40	0.0	0.0
Monocytes rest	0.0	0.0
Monocytes LPS	0.0	0.0
Macrophages rest	0.0	0.0
Macrophages LPS	0.0	0.0
HUVEC none	0.0	0.0
HUVEC starved	0.0	0.0
HUVEC IL-1beta	0.0	0.0
HUVEC IFN gamma	0.0	0.0
HUVEC TNF alpha + IFN gamma	0.0	0.0
HUVEC TNF alpha + IL4	0.0	0.0
HUVEC IL-11	0.0	0.0
Lung Microvascular EC none	0.0	0.0
Lung Microvascular EC TNFalpha + IL-1beta	0.0	0.0
Microvascular Dermal EC none	0.0	0.0
Microsvasular Dermal EC TNFalpha + IL-1beta	0.0	0.0
Bronchial epithelium TNFalpha + IL1beta	2.3	4.0
Small airway epithelium none	3.7	3.2
Small airway epithelium TNFalpha + IL-1beta	2.5	1.2
Coronery artery SMC rest	0.0	0.0
Coronery artery SMC TNFalpha + IL-1beta	0.0	0.0
Astrocytes rest	1:9	2.5
Astrocytes TNFalpha + IL-1beta	0.0	0.0
KU-812 (Basophil) rest	11.3	1.7
KU-812 (Basophil) PMA/ionomycin	61.1	100.0
CCD1106 (Keratinocytes) none	100.0	71.7
CCD1106 (Keratinocytes) TNFalpha + IL-1beta	7.6	4.0
Liver cirrhosis	0.8	0.2
NCI-H292 none	7.2	6.4
NCI-H292 IL-4	4.6	6.8
NCI-H292 IL-9	25.0	8.4
NCI-H292 IL-13	9.7	7.8
NCI-H292 IFN gamma	2.8	1.9
HPAEC none	0.0	0.0
HPAEC TNF alpha + IL-1 beta	0.0	0.0
Lung fibroblast none	85.3	53.6
Lung fibroblast TNF alpha + IL-1 beta	35.1	31.0
Lung fibroblast IL-4	20.7	7.8
Lung fibroblast IL-9	2.8	7.3
Lung fibroblast IL-13	11.4	3.0
Lung fibroblast IFN gamma	52.1	38.2
Dermal fibroblast CCD1070 rest	0.3	0.0
Dermal fibroblast CCD1070 TNF alpha	0.0	1.0
Dermal fibroblast CCD1070 IL-1 beta	0.0	0.0
Dermal fibroblast IFN gamma	0.0	0.0
Dermal fibroblast IL-4	0.0	0.0
Dermal Fibroblasts rest	0.0	0.0
Neutrophils TNFa + LPS	0.0	0.0
Neutrophils rest	0.0	0.0
Colon	1.5	0.5
Lung	1.1	0.7
Thymus	1.4	0.0
Kidney	1.6	0.0
Column A - Rel. Exp. (%) Ag6719, Run 276596890
Column B - Rel. Exp. (%) Ag6725, Run 276846995

[0679]

TABLE FL
Panel 4D
Tissue Name                      A
Secondary Th1 act                0.0
Secondary Th2 act                0.1
Secondary Tr1 act                0.0
Secondary Th1 rest               0.0
Secondary Th2 rest               0.0
Secondary Tr1 rest               0.0
Primary Th1 act                  0.0
Primary Th2 act                  0.0
Primary Tr1 act                  0.0
Primary Th1 rest                 0.0
Primary Th2 rest                 0.0
Primary Tr1 rest                 0.0
CD45RA CD4 lymphocyte act        0.0
CD45RO CD4 lymphocyte act        0.0
CD8 lymphocyte act               0.0
Secondary CD8 lymphocyte rest    0.0
Secondary CD8 lymphocyte act     0.3
CD4 lymphocyte none              0.0
2ry Th1/Th2/Tr1_anti-CD95 CH11   0.0
LAK cells rest                   0.0
LAK cells IL-2                   0.0
LAK cells IL-2 + IL-12           4.2
LAK cells IL-2 + IFN gamma       0.0
LAK cells IL-2 + IL-18           0.0
LAK cells PMA/ionomycin          0.0
NK Cells IL-2 rest               0.0
Two Way MLR 3 day                0.0
Two Way MLR 5 day                0.0
Two Way MLR 7 day                0.0
PBMC rest                        0.0
PBMC PWM                         0.0
PBMC PHA-L                       0.0
Ramos (B cell) none              0.0
Ramos (B cell) ionomycin         0.3
B lymphocytes PWM                0.0
B lymphocytes CD40L and IL-4     0.0
EOL-1 dbcAMP                     0.0
EOL-1 dbcAMP PMA/ionomycin       0.0
Dendritic cells none             0.0
Dendritic cells LPS              0.0
Dendritic cells anti-CD40        0.0
Monocytes rest                   0.0
Monocytes LPS                    0.0
Macrophages rest                 41.8
Macrophages LPS                  0.1
HUVEC none                       1.7
HUVEC starved                    0.0
HUVEC IL-1beta                   0.0
HUVEC IFN gamma                  0.0
HUVEC TNF alpha + IFN gamma      0.0
HUVEC TNF alpha + IL4            0.3
HUVEC IL-11                      0.0
Lung Microvascular EC none       0.0
Lung Microvascular EC TNFalpha + IL-1beta 0.0
Microvascular Dermal EC none     0.0
Microsvasular Dermal EC TNFalpha + IL-1beta 0.0
Bronchial epithelium TNFalpha + IL1beta 3.7
Small airway epithelium none     4.5
Small airway epithelium TNFalpha + IL-1beta 1.7
Coronery artery SMC rest         0.0
Coronery artery SMC TNFalpha + IL-1beta 0.0
Astrocytes rest                  8.5
Astrocytes TNFalpha + IL-1beta   0.2
KU-812 (Basophil) rest           8.3
KU-812 (Basophil) PMA/ionomycin  100.0
CCD1106 (Keratinocytes) none     70.2
CCD1106 (Keratinocytes) TNFalpha + IL-1beta 3.0
Liver cirrhosis                  1.3
Lupus kidney                     0.0
NCI-H292 none                    16.6
NCI-H292 IL-4                    10.4
NCI-H292 IL-9                    20.2
NCI-H292 IL-13                   6.3
NCI-H292 IFN gamma               8.5
HPAEC none                       0.0
HPAEC TNF alpha + IL-1 beta      0.0
Lung fibroblast none             36.3
Lung fibroblast TNF alpha + IL-1 beta 18.6
Lung fibroblast IL-4             16.0
Lung fibroblast IL-9             4.4
Lung fibroblast IL-13            11.4
Lung fibroblast IFN gamma        36.9
Dermal fibroblast CCD1070 rest   0.1
Dermal fibroblast CCD1070 TNF alpha 0.0
Dermal fibroblast CCD1070 IL-1 beta 0.0
Dermal fibroblast IFN gamma      0.3
Dermal fibroblast IL-4           0.0
IBD Colitis 2                    0.3
IBD Crohn's                      0.3
Colon                            11.4
Lung                             5.3
Thymus                           1.2
Kidney                           2.0
Column A - Rel. Exp. (%) Ag1094, Run 145854199

[0680]

TABLE FM
Panel CNS_1.1
	Tissue Name	A	B
	Cing Gyr Depression2	0.0	0.0
	Cing Gyr Depression	0.0	0.0
	Cing Gyr PSP2	0.0	0.0
	Cing Gyr PSP	9.7	0.0
	Cing Gyr Huntington's2	3.6	0.0
	Cing Gyr Huntington's	0.0	0.0
	Cing Gyr Parkinson's2	0.0	0.0
	Cing Gyr Parkinson's	0.0	0.0
	Cing Gyr Alzheimer's2	0.0	0.0
	Cing Gyr Alzheimer's	0.0	0.0
	Cing Gyr Control2	0.0	7.0
	Cing Gyr Control	8.2	0.0
	Temp Pole Depression2	0.0	0.0
	Temp Pole PSP2	0.0	0.0
	Temp Pole PSP	0.0	0.0
	Temp Pole Huntington's	0.0	0.0
	Temp Pole Parkinson's2	0.0	0.0
	Temp Pole Parkinson's	6.0	10.9
	Temp Pole Alzheimer's2	0.0	0.0
	Temp Pole Alzheimer's	0.0	0.0
	Temp Pole Control2	4.5	0.0
	Temp Pole Control	0.0	6.0
	Glob Palladus Depression	0.0	0.0
	Glob Palladus PSP2	12.8	6.0
	Glob Palladus PSP	0.0	2.6
	Glob Palladus Parkinson's2	17.1	29.1
	Glob Palladus Parkinson's	100.0	100.0
	Glob Palladus Alzheimer's2	2.5	2.3
	Glob Palladus Alzheimer's	3.2	5.8
	Glob Palladus Control2	3.7	19.9
	Glob Palladus Control	17.0	12.3
	Sub Nigra Depression2	7.4	0.0
	Sub Nigra Depression	7.2	0.0
	Sub Nigra PSP2	8.4	0.0
	Sub Nigra Huntington's2	0.0	13.0
	Sub Nigra Huntington's	50.0	15.9
	Sub Nigra Parkinson's2	34.6	30.1
	Sub Nigra Alzheimer's2	0.0	6.7
	Sub Nigra Control2	34.6	40.1
	Sub Nigra Control	12.3	22.1
	BA17 Depression2	0.0	0.0
	BA17 Depression	0.0	0.0
	BA17 PSP2	0.0	0.0
	BA17 PSP	0.0	0.0
	BA17 Huntington's2	0.0	0.0
	BA17 Huntington's	0.0	0.0
	BA17 Parkinson's2	0.0	6.2
	BA17 Parkinson's	0.0	0.0
	BA17 Alzheimer's2	0.0	0.0
	BA17 Control2	0.0	0.0
	BA17 Control	0.0	0.0
	BA9 Depression2	0.0	2.7
	BA9 Depression	0.0	0.0
	BA9 PSP2	0.0	0.0
	BA9 PSP	0.0	0.0
	BA9 Huntington's2	0.0	0.0
	BA9 Huntington's	0.0	0.0
	BA9 Parkinson's2	0.0	0.0
	BA9 Parkinson's	0.0	0.0
	BA9 Alzheimer's2	0.0	0.0
	BA9 Alzheimer's	0.0	0.0
	BA9 Control2	14.5	18.3
	BA9 Control	0.0	0.0
	BA7 Depression	0.0	0.0
	BA7 PSP2	0.0	0.0
	BA7 PSP	0.0	0.0
	BA7 Huntington's2	11.7	7.2
	BA7 Huntington's	0.0	0.0
	BA7 Parkinson's2	0.0	0.0
	BA7 Parkinson's	0.0	0.0
	BA7 Alzheimer's2	0.0	0.0
	BA7 Control2	0.0	5.7
	BA7 Control	0.0	0.0
	BA4 Depression2	0.0	0.0
	BA4 Depression	7.7	6.2
	BA4 PSP2	0.0	0.0
	BA4 PSP	0.0	0.0
	BA4 Huntington's2	0.0	0.0
	BA4 Huntington's	0.0	0.0
	BA4 Parkinson's2	0.0	0.0
	BA4 Parkinson's	0.0	0.0
	BA4 Alzheimer's2	0.0	0.0
	BA4 Control2	0.0	0.0
	BA4 Control	0.0	0.0
	Column A - Rel. Exp. (%) Ag6725, Run 281869490
	Column B - Rel. Exp. (%) Ag6725, Run 312089390

[0681] Ardais Panel v.1.0 Summary: Ag1094 The highest expression of this gene in this panel is seen in a lung cancer sample (CT=23.5). Expression of this gene is higher in 4 cancer samples compared to normal lung samples. Therefore, expression of this gene will be used as a marker to detect the presence of lung cancer and also, therapeutic modulation of this gene or its protein product will be useful in the treatment of lung cancer.

[0682] General_screening_panel_v1.6 Summary: Ag6719 Highest expresion of this gene is seen in SHP-77 lung cancer cell line (CT=26.6). Expression is higher in brain, lung, colon, gastric, ovarian and prostate cancer cell lines compared to normal tissues. Therefore, expression of this gene will be used as marker to detect the presence of these cancers and also, therapeutic modulation of this gene or its protein product will be useful in the treatment of these cancers.

[0683] Low expression of this gene is also seen in fetal brain and thalamus. Therefore, therapeutic modulation of this gene will be useful in the treatment of neurological disorders related to thalamus and brain development.

[0684] Low expression of this gene is also seen in fetal lung, fetal kidney, and fetal heart. Expression is higher in these fetal tissues compared to the corresponding adult tissues. Thus, this gene may play a role in early development of these tissue. Therefore, therapeutic modulation of this gene or its protein product will be useful in the treatment of diseases related to development of these tissues.

[0685] Panel 1 Summary: Ag273b Expression of this gene is highest in a metastatic prostate cancer cell line PC-3 (CT =26.8). There is also substantial expression in lung and brain cancer cell lines. Thus, expression of this gene could be used as marker to identify or detect the presence of lung, prostate or brain cancers. In addition, therapeutic inhibition of this gene product, for example, through the use of small molecule drugs or antibodies, is useful in the treatment of lung, prostate or brain cancers. Among normal tissues, this gene is low to moderately expressed in heart, colon, small intestine, trachea, salivary gland, fetal liver, and mammary gland.

[0686] This gene encodes a novel insulin-like growth factor binding protein acid labile subunit. Among central nervous system (CNS) tissues, this gene is expressed at moderate to low levels in cerebellum and thalamus. Insulin-like growth factor (IGF) has been shown to have neuroprotective effects and is currently under investigation as a biopharmaceutical for the treatment of amyotropic lateral sclerosis (Mewar R., McMorris F. A., 1997, Expression of insulin-like growth factor-binding protein messenger RNAs in developing rat oligodendrocytes and astrocytes. J. Neurosci. Res 50:721-728, PMID: 9418960; Arnold P. M., Ma J. Y., Citron B. A., Zoubine M. N., Festoff B. W., 2000, Selective developmental regulation of gene expression for insulin-like growth factor-binding proteins in mouse spinal cord. Spine 25:1765-1770, PMID: 10888943; Corse A. M., Bilak M. M., Bilak S. R., Lehar M., Rothstein J. D., Kuncl R. W. (1999) Preclinical testing of neuroprotective neurotrophic factors in a model of chronic motor neuron degeneration. Neurobiol. Dis. 6:335-346). In serum, IGF is bound to both IGF-binding protein (IGFBP) and the acid labile subunit (IGFBP-ALS). In the brain, glia produce IGFBP; however the IGFBP-ALS has not been detected in the CNS. Therefore, this gene may represent the CNS equivalent of IGFBP-ALS. Because of the neuroprotective effects of IGF, therapeutic modulation of this gene or its protein product will be useful in treating diseases in which neuronal cell death/degeneration occur such as amyotropic lateral sclerosis, multiple sclerosis, Alzheimer's disease, Parkinson's disease, Huntington's disease, spinocerebellar ataxia, or CNS injury such as stroke, head or spinal cord trauma.

[0687] Panel 1.3D Summary: Expression of this gene is highest in a SHP-77 lung cancer cell line (CT=28) in this panel. There is also substantial expression of this gene in other lung, brain and metastatic prostate cancer cell lines. Among CNS tissues, there is low but significant expression in thalamus and cerebellum.

[0688] Panel 2D Summary: Expression of this gene is highest in a metastatic breast cancer sample (CT=26-27). In addition, several other breast and lung cancer samples show higher expression than the normal adjacent margin samples. Thus, expression of this gene will be used to distinguish breast or lung cancer tissue from normal tissue and will be of diagnostic value. Moreover, therapeutic modulation of the this gene or its gene product, for example, through the use of small molecule drugs or antibodies, will be of benefit for treatment of breast or lung cancer.

[0689] Panel 3D Summary: Expression of this gene is highest in NCI-H146 small cell lung cancer cell line (CT=28.5). In addition, there is significant expression of this gene in other lung, brain and pancreatic cancer cell lines. These results are consistent with what is observed in the other panels. Thus, the expression of this gene will be used to distinguish lung, breast or pancreas cancer cell line samples from other tissues. Moreover, therapeutic modulation of this gene or gene product, through the use of small molecule drugs or antibodies, will be of benefit for treatment of lung, breast or pancreatic cancer.

[0690] Panel 4.1D Summary: Highest expression of this gene is seen in activated basophils and resting keratinocytes (CTs=30-31). Significant expression of this gene is also seen in resting basophils, activated keratinocytes, activated NCI-H292, resting and activated lung fibroblasts.

[0691] Panel 4D Summary: Ag1094 This gene is expressed at high levels in basophils (CT 28.3) as well as in keratinocytes and normal lung fibroblasts (independent of their activation status). Tthis gene is expressed at a lower level in a muco-epidermoid cell line (H292). Expression of the 83420733_EXT gene is also found in normal lung which is consistent with the data from Panel 1.3D. This gene will be a suitable target to modulate locally the mitogenic effect of IGF and could be useful in the treatment of emphysema, COPD, or skin related disease.

[0692] Panel CNS—1.1 Summary: Low expression of this gene was detected in globus pallidus sample derived from a Parkinson's disease patient (CTs=33-34). Therefore, therapeutic modulation of this gene or its protein product will be useful in the treatment of Parkinson's disease.

G. NOV 7, CG55690-01: FZD-9

[0693] Expression of gene CG55690-01 was assessed using the primer-probe sets Ag2256 and Ag4933, described in Tables GA and GB. Results of the RTQ-PCR runs are shown in Tables GC, GD, GE, GF, GG, GU.

TABLE GA
Probe Name Ag2256
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-cacgcactgccactataagg-3′	20	1717	213
Probe	TET-5′-cttgcacatgactaagacggacccct-3′-	26	1750	214
TAMRA
Reverse	5′-ctagaggtgtgtggggttctc-3′	21	1781	215

[0694]

TABLE GB
Probe Name Ag4933
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-cacgcactgccactataagg-3′	20	1717	216
Probe	TET-5′-cttgcacatgactaagacggacccct-3′-	26	1750	217
	TAMRA
Reverse	5′-ctagaggtgtgtggggttctc-3′	21	1781	218

[0695]

TABLE GC
General_screening_panel_v1.5
	Tissue Name	A	B
	Adipose	8.1	4.3
	Melanoma* Hs688(A).T	4.1	4.3
	Melanoma* Hs688(B).T	1.0	2.8
	Melanoma* M14	19.6	27.0
	Melanoma* LOXIMVI	0.9	0.0
	Melanoma* SK-MEL-5	30.6	24.7
	Squamous cell carcinoma SCC-4	0.4	0.0
	Testis Pool	6.2	9.6
	Prostate ca.* (bone met) PC-3	3.6	3.3
	Prostate Pool	3.6	2.6
	Placenta	5.3	2.2
	Uterus Pool	0.2	0.0
	Ovarian ca. OVCAR-3	2.5	5.4
	Ovarian ca. SK-OV-3	17.2	13.6
	Ovarian ca. OVCAR-4	11.3	12.9
	Ovarian ca. OVCAR-5	15.0	10.2
	Ovarian ca. IGROV-1	3.2	12.1
	Ovarian ca. OVCAR-8	25.9	36.9
	Ovary	1.1	0.3
	Breast ca. MCF-7	4.0	1.9
	Breast ca. MDA-MB-231	0.9	1.0
	Breast ca. BT 549	7.7	17.4
	Breast ca. T47D	3.8	6.9
	Breast ca. MDA-N	0.0	0.0
	Breast Pool	0.7	0.0
	Trachea	14.9	15.8
	Lung	0.0	0.0
	Fetal Lung	3.5	4.6
	Lung ca. NCI-N417	17.9	41.8
	Lung ca. LX-1	4.6	6.0
	Lung ca. NCI-H146	100.0	100.0
	Lung ca. SHP-77	2.3	3.0
	Lung ca. A549	0.0	4.6
	Lung ca. NCI-H526	6.0	2.5
	Lung ca. NCI-H23	26.8	35.4
	Lung ca. NCI-H460	27.9	29.9
	Lung ca. HOP-62	0.0	3.0
	Lung ca. NCI-H522	16.7	17.4
	Liver	0.1	2.4
	Fetal Liver	6.2	4.6
	Liver ca. HepG2	4.7	8.2
	Kidney Pool	1.8	4.2
	Fetal Kidney	2.0	0.0
	Renal ca. 786-0	0.0	0.0
	Renal ca. A498	4.6	6.7
	Renal ca. ACHN	1.1	3.5
	Renal ca. UO-31	2.2	7.6
	Renal ca. TK-10	4.1	6.5
	Bladder	2.6	2.0
	Gastric ca. (liver met.) NCI-N87	0.3	0.0
	Gastric ca. KATO III	0.0	0.0
	Colon ca. SW-948	5.2	1.0
	Colon ca. SW480	48.0	79.0
	Colon ca.* (SW480 met) SW620	31.4	31.6
	Colon ca. HT29	0.0	1.4
	Colon ca. HCT-116	7.6	7.5
	Colon ca. CaCo-2	2.3	9.7
	Colon cancer tissue	0.8	2.2
	Colon ca. SW1116	0.0	0.0
	Colon ca. Colo-205	0.0	0.0
	Colon ca. SW-48	0.0	1.1
	Colon Pool	3.4	5.3
	Small Intestine Pool	2.7	1.0
	Stomach Pool	0.0	1.0
	Bone Marrow Pool	0.8	1.9
	Fetal Heart	0.0	0.0
	Heart Pool	0.0	0.2
	Lymph Node Pool	4.2	2.1
	Fetal Skeletal Muscle	6.2	8.9
	Skeletal Muscle Pool	23.2	30.1
	Spleen Pool	0.8	1.1
	Thymus Pool	2.1	0.9
	CNS cancer (glio/astro) U87-MG	0.0	0.0
	CNS cancer (glio/astro) U-118-MG	0.0	0.0
	CNS cancer (neuro; met) SK-N-AS	0.7	0.0
	CNS cancer (astro) SF-539	2.6	7.0
	CNS cancer (astro) SNB-75	15.5	16.8
	CNS cancer (glio) SNB-19	13.5	16.5
	CNS cancer (glio) SF-295	0.0	0.0
	Brain (Amygdala) Pool	11.4	13.3
	Brain (cerebellum)	21.0	19.5
	Brain (fetal)	11.9	18.4
	Brain (Hippocampus) Pool	7.3	7.1
	Cerebral Cortex Pool	6.2	7.6
	Brain (Substantia nigra) Pool	13.7	11.0
	Brain (Thalamus) Pool	9.8	11.7
	Brain (whole)	8.5	17.7
	Spinal Cord Pool	17.1	15.3
	Adrenal Gland	0.7	2.6
	Pituitary gland Pool	3.1	8.0
	Salivary Gland	1.6	8.0
	Thyroid (female)	1.6	2.7
	Pancreatic ca. CAPAN2	0.0	0.0
	Pancreas Pool	2.1	4.2
	Column A - Rel. Exp. (%) Ag2256, Run 229393821
	Column B - Rel. Exp. (%) Ag4933, Run 228843452

[0696]

TABLE GD
HASS Panel v1.0
Tissue Name               A
MCF-7 C1                  19.1
MCF-7 C2                  11.6
MCF-7 C3                  3.1
MCF-7 C4                  17.9
MCF-7 C5                  4.8
MCF-7 C6                  11.3
MCF-7 C7                  3.2
MCF-7 C9                  0.0
MCF-7 C10                 12.7
MCF-7 C11                 3.0
MCF-7 C12                 4.6
MCF-7 C13                 4.0
MCF-7 C15                 3.3
MCF-7 C16                 21.6
MCF-7 C17                 22.8
T24 D1                    0.0
T24 D2                    0.0
T24 D3                    0.0
T24 D4                    0.0
T24 D5                    0.0
T24 D6                    1.0
T24 D7                    0.0
T24 D9                    0.0
T24 D10                   0.0
T24 D11                   0.0
T24 D12                   0.0
T24 D13                   0.0
T24 D15                   0.0
T24 D16                   1.3
T24 D17                   0.0
CAPaN B1                  0.0
CAPaN B2                  0.0
CAPaN B3                  0.0
CAPaN B4                  0.0
CAPaN B5                  0.0
CAPaN B6                  0.0
CAPaN B7                  0.0
CAPaN B8                  0.0
CAPaN B9                  0.0
CAPaN B10                 0.0
CAPaN B11                 0.0
CAPaN B12                 0.0
CAPaN B13                 0.0
CAPaN B14                 0.0
CAPaN B15                 0.0
CAPaN B16                 0.0
CAPaN B17                 0.0
U87-MG F1 (B)             0.0
U87-MG F2                 0.0
U87-MG F3                 0.0
U87-MG F4                 0.0
U87-MG F5                 0.0
U87-MG F6                 0.0
U87-MG F7                 0.0
U87-MG F8                 0.0
U87-MG F9                 0.0
U87-MG F10                0.0
U87-MG F11                0.0
U87-MG F12                0.0
U87-MG F13                0.0
U87-MG F14                1.0
U87-MG F15                1.4
U87-MG F16                0.0
U87-MG F17                0.0
LnCAP A1                  55.1
LnCAP A2                  41.2
LnCAP A3                  40.1
LnCAP A4                  11.5
LnCAP A5                  27.7
LnCAP A6                  61.1
LnCAP A7                  3.5
LnCAP A8                  14.1
LnCAP A9                  12.2
LnCAP A10                 73.2
LnCAP A11                 81.8
LnCAP A12                 52.5
LnCAP A13                 17.9
LnCAP A14                 14.4
LnCAP A15                 13.9
LnCAP A16                 37.1
LnCAP A17                 65.1
Primary Astrocytes        8.6
Primary Renal Proximal    0.0
Tubule Epithelial cell A2
Primary melanocytes A5    27.2
126443 - 341 medullo      2.4
126444 - 487 medullo      19.9
126445 - 425 medullo      1.4
126446 - 690 medullo      9.8
126447 - 54 adult glioma  0.0
126448 - 245 adult glioma 3.5
126449 - 317 adult glioma 2.1
126450 - 212 glioma       3.1
126451 - 456 glioma       100.0
Column A - Rel. Exp. (%) Ag2256, Run 268366851

[0697]

TABLE GE
Panel 1.3D
	Tissue Name	A	B
	Liver adenocarcinoma	0.0	0.0
	Pancreas	0.0	0.9
	Pancreatic ca. CAPAN 2	0.0	0.0
	Adrenal gland	3.2	4.1
	Thyroid	0.0	0.0
	Salivary gland	7.9	5.5
	Pituitary gland	12.2	1.7
	Brain (fetal)	1.3	1.6
	Brain (whole)	11.7	20.2
	Brain (amygdala)	18.8	31.0
	Brain (cerebellum)	0.0	0.0
	Brain (hippocampus)	85.9	95.3
	Brain (substantia nigra)	8.9	10.9
	Brain (thalamus)	70.7	39.5
	Cerebral Cortex	17.1	11.9
	Spinal cord	2.7	4.0
	glio/astro U87-MG	0.0	0.9
	glio/astro U-118-MG	0.0	0.0
	astrocytoma SW1783	12.4	12.4
	neuro*; met SK-N-AS	0.0	0.0
	astrocytoma SF-539	1.6	7.0
	astrocytoma SNB-75	0.0	4.5
	glioma SNB-19	0.0	0.0
	glioma U251	0.0	0.0
	glioma SF-295	0.0	0.0
	Heart (fetal)	1.1	2.1
	Heart	0.0	0.0
	Skeletal muscle (fetal)	100.0	100.0
	Skeletal muscle	1.1	11.7
	Bone marrow	2.9	0.0
	Thymus	0.0	2.3
	Spleen	0.6	0.0
	Lymph node	1.3	3.4
	Colorectal	5.4	0.0
	Stomach	0.6	2.9
	Small intestine	15.6	11.7
	Colon ca. SW480	15.9	33.2
	Colon ca.* SW620(SW480 met)	1.3	0.0
	Colon ca. HT29	0.0	0.0
	Colon ca. HCT-116	0.0	0.0
	Colon ca. CaCo-2	1.2	1.3
	Colon ca. tissue(ODO3866)	0.0	0.0
	Colon ca. HCC-2998	8.9	13.6
	Gastric ca.* (liver met) NCI-N87	0.0	2.3
	Bladder	0.0	2.6
	Trachea	18.4	15.5
	Kidney	0.0	1.0
	Kidney (fetal)	1.3	1.8
	Renal ca. 786-0	1.0	0.0
	Renal ca. A498	0.5	4.7
	Renal ca. RXF 393	0.0	0.0
	Renal ca. ACHN	1.4	2.3
	Renal ca. UO-31	0.0	6.1
	Renal ca. TK-10	0.0	0.0
	Liver	0.0	0.0
	Liver (fetal)	1.2	12.9
	Liver ca. (hepatoblast) HepG2	2.1	0.0
	Lung	1.2	0.0
	Lung (fetal)	2.8	2.2
	Lung ca. (small cell) LX-1	0.0	4.4
	Lung ca. (small cell) NCI-H69	23.5	30.8
	Lung ca. (s. cell var.) SHP-77	0.2	3.8
	Lung ca. (large cell)NCI-H460	8.5	2.9
	Lung ca. (non-sm. cell) A549	1.6	2.2
	Lung ca. (non-s. cell) NCI-H23	8.8	13.6
	Lung ca. (non-s. cell) HOP-62	0.0	1.7
	Lung ca. (non-s. cl) NCI-H522	6.0	10.1
	Lung ca. (squam.) SW 900	1.0	4.7
	Lung ca. (squam.) NCI-H596	31.9	27.9
	Mammary gland	0.0	5.1
	Breast ca.* (pl. ef) MCF-7	0.0	0.0
	Breast ca.* (pl. ef) MDA-MB-231	0.0	0.0
	Breast ca.* (pl. ef) T47D	2.5	3.4
	Breast ca. BT-549	7.3	6.3
	Breast ca. MDA-N	0.0	0.0
	Ovary	2.1	4.5
	Ovarian ca. OVCAR-3	0.0	2.0
	Ovarian ca. OVCAR-4	1.3	2.0
	Ovarian ca. OVCAR-5	0.0	0.0
	Ovarian ca. OVCAR-8	3.2	0.0
	Ovarian ca. IGROV-1	0.0	0.0
	Ovarian ca.* (ascites) SK-OV-3	1.5	2.0
	Uterus	1.1	1.1
	Placenta	2.1	2.5
	Prostate	5.7	11.6
	Prostate ca.* (bone met)PC-3	1.1	0.0
	Testis	40.9	85.3
	Melanoma Hs688(A).T	2.3	0.0
	Melanoma* (met) Hs688(B).T	1.3	5.7
	Melanoma UACC-62	6.8	2.2
	Melanoma M14	7.7	14.6
	Melanoma LOX IMVI	0.0	0.0
	Melanoma* (met) SK-MEL-5	3.7	9.2
	Adipose	2.4	2.3
	Column A - Rel. Exp. (%) Ag2256, Run 148422104
	Column B - Rel. Exp. (%) Ag2256, Run 148493664

[0698]

TABLE GF
Panel 2D
Tissue Name	A	B
Normal Colon	3.3	5.0
CC Well to Mod Diff (ODO3866)	5.7	1.0
CC Margin (ODO3866)	15.4	5.8
CC Gr.2 rectosigmoid (ODO3868)	0.0	0.0
CC Margin (ODO3868)	0.0	4.7
CC Mod Diff (ODO3920)	1.6	11.1
CC Margin (ODO3920)	0.0	2.5
CC Gr.2 ascend colon (ODO3921)	16.7	2.2
CC Margin (ODO3921)	5.6	4.3
CC from Partial Hepatectomy (ODO4309) Mets	2.5	0.0
Liver Margin (ODO4309)	7.7	0.0
Colon mets to lung (OD04451-01)	39.2	31.6
Lung Margin (OD04451-02)	0.0	0.0
Normal Prostate 6546-1	21.9	19.3
Prostate Cancer (OD04410)	10.6	14.9
Prostate Margin (OD04410)	48.3	30.1
Prostate Cancer (OD04720-01)	14.1	5.0
Prostate Margin (OD04720-02)	21.5	20.7
Normal Lung 061010	6.8	9.0
Lung Met to Muscle (ODO4286)	0.0	1.1
Muscle Margin (ODO4286)	24.0	9.3
Lung Malignant Cancer (OD03126)	5.4	0.0
Lung Margin (OD03126)	9.7	4.9
Lung Cancer (OD04404)	13.7	11.7
Lung Margin (OD04404)	3.0	2.4
Lung Cancer (OD04565)	0.0	0.0
Lung Margin (OD04565)	0.0	0.0
Lung Cancer (OD04237-01)	100.0	100.0
Lung Margin (OD04237-02)	0.0	0.0
Ocular Mel Met to Liver (ODO4310)	77.9	73.2
Liver Margin (ODO4310)	0.0	3.0
Melanoma Mets to Lung (OD04321)	39.5	39.8
Lung Margin (OD04321)	0.0	4.9
Normal Kidney	6.0	4.1
Kidney Ca, Nuclear grade 2 (OD04338)	2.9	12.9
Kidney Margin (OD04338)	3.7	0.0
Kidney Ca Nuclear grade 1/2 (OD04339)	0.0	0.0
Kidney Margin (OD04339)	2.3	0.0
Kidney Ca, Clear cell type (OD04340)	2.5	4.0
Kidney Margin (OD04340)	9.3	4.2
Kidney Ca, Nuclear grade 3 (OD04348)	0.0	0.0
Kidney Margin (OD04348)	2.9	0.0
Kidney Cancer (OD04622-01)	11.3	2.3
Kidney Margin (OD04622-03)	0.0	0.0
Kidney Cancer (OD04450-01)	12.7	18.6
Kidney Margin (OD04450-03)	0.0	0.0
Kidney Cancer 8120607	3.1	4.8
Kidney Margin 8120608	6.7	0.0
Kidney Cancer 8120613	0.0	0.0
Kidney Margin 8120614	0.0	0.0
Kidney Cancer 9010320	6.2	0.0
Kidney Margin 9010321	3.1	2.5
Normal Uterus	6.3	0.0
Uterus Cancer 064011	0.0	0.0
Normal Thyroid	8.3	4.9
Thyroid Cancer 064010	2.9	0.0
Thyroid Cancer A302152	0.0	0.0
Thyroid Margin A302153	6.1	10.3
Normal Breast	12.9	5.9
Breast Cancer (OD04566)	2.6	3.9
Breast Cancer (OD04590-01)	0.0	1.9
Breast Cancer Mets (OD04590-03)	6.0	13.5
Breast Cancer Metastasis (OD04655-05)	8.4	0.0
Breast Cancer 064006	0.0	5.0
Breast Cancer 1024	3.2	6.5
Breast Cancer 9100266	0.0	0.0
Breast Margin 9100265	3.1	0.0
Breast Cancer A209073	3.4	3.2
Breast Margin A209073	6.7	6.0
Normal Liver	0.0	0.0
Liver Cancer 064003	5.1	0.0
Liver Cancer 1025	0.0	0.0
Liver Cancer 1026	5.0	25.9
Liver Cancer 6004-T	0.0	0.0
Liver Tissue 6004-N	5.0	11.8
Liver Cancer 6005-T	16.2	18.4
Liver Tissue 6005-N	0.0	0.0
Normal Bladder	4.5	2.7
Bladder Cancer 1023	0.0	1.1
Bladder Cancer A302173	7.3	11.0
Bladder Cancer (OD04718-01)	3.7	0.0
Bladder Normal Adjacent (OD04718-03)	1.4	5.4
Normal Ovary	4.0	8.0
Ovarian Cancer 064008	8.1	2.7
Ovarian Cancer (OD04768-07)	13.7	11.4
Ovary Margin (OD04768-08)	1.6	2.0
Normal Stomach	7.6	1.5
Gastric Cancer 9060358	1.7	0.0
Stomach Margin 9060359	5.6	0.0
Gastric Cancer 9060395	0.0	2.5
Stomach Margin 9060394	3.5	2.7
Gastric Cancer 9060397	0.0	0.0
Stomach Margin 9060396	0.0	0.0
Gastric Cancer 064005	0.0	0.0
Column A - Rel. Exp. (%) Ag2256, Run 148422111
Column B - Rel. Exp. (%) Ag2256, Run 148493675

[0699]

TABLE GG
Panel 3D
Tissue Name                      A
Daoy- Medulloblastoma            0.5
TE671- Medulloblastoma           5.3
D283 Med- Medulloblastoma        7.0
PFSK-1- Primitive Neuroectodermal 1.5
XF-498- CNS                      0.0
SNB-78- Glioma                   0.0
SF-268- Glioblastoma             2.0
T98G- Glioblastoma               0.0
SK-N-SH- Neuroblastoma (metastasis) 15.8
SF-295- Glioblastoma             0.0
Cerebellum                       6.4
Cerebellum                       6.5
NCI-H292- Mucoepidermoid lung carcinoma 0.0
DMS-114- Small cell lung cancer  22.2
DMS-79- Small cell lung cancer   0.0
NCI-H146- Small cell lung cancer 100.0
NCI-H526- Small cell lung cancer 9.5
NCI-N417- Small cell lung cancer 26.1
NCI-H82- Small cell lung cancer  1.7
NCI-H157- Squamous cell lung cancer (metastasis) 0.0
NCI-H1155- Large cell lung cancer 24.5
NCI-H1299- Large cell lung cancer 14.9
NCI-H727- Lung carcinoid         1.8
NCI-UMC-11- Lung carcinoid       1.7
LX-1- Small cell lung cancer     6.3
Colo-205- Colon cancer           0.0
KM 12- Colon cancer              4.4
KM20L2- Colon cancer             0.0
NCI-H716- Colon cancer           7.2
SW-48- Colon adenocarcinoma      0.0
SW1116- Colon adenocarcinoma     0.0
LS 174T- Colon adenocarcinoma    0.0
SW-948- Colon adenocarcinoma     0.0
SW-480- Colon adenocarcinoma     0.0
NCI-SNU-5- Gastric carcinoma     6.7
KATO III- Gastric carcinoma      23.2
NCI-SNU-16- Gastric carcinoma    0.0
NCI-SNU-1- Gastric carcinoma     0.0
RF-1- Gastric adenocarcinoma     0.9
RF-48- Gastric adenocarcinoma    0.0
MKN-45- Gastric carcinoma        0.0
NCI-N87- Gastric carcinoma       0.0
OVCAR-5- Ovarian carcinoma       0.3
RL95-2- Uterine carcinoma        2.0
HelaS3- Cervical adenocarcinoma  0.0
Ca Ski- Cervical epidermoid carcinoma 12.8
(metastasis)
ES-2- Ovarian clear cell carcinoma 1.0
Ramos- Stimulated with PMA/ionomycin 6 h 0.0
Ramos- Stimulated with PMA/ionomycin 14 h 0.0
MEG-01- Chronic myelogenous leukemia 0.0
(megokaryoblast)
Raji- Burkitt's lymphoma         0.0
Daudi- Burkitt's lymphoma        0.0
U266- B-cell plasmacytoma        0.2
CA46- Burkitt's lymphoma         0.0
RL- non-Hodgkin's B-cell lymphoma 0.0
JM1- pre-B-cell lymphoma         0.0
Jurkat- T cell leukemia          0.0
TF-1- Erythroleukemia            0.7
HUT 78- T-cell lymphoma          0.0
U937- Histiocytic lymphoma       3.6
KU-812- Myelogenous leukemia     0.0
769-P- Clear cell renal carcinoma 0.0
Caki-2- Clear cell renal carcinoma 0.9
SW 839- Clear cell renal carcinoma 0.0
Rhabdoid kidney tumor            0.0
Hs766T- Pancreatic carcinoma (LN metastasis) 0.0
CAPAN-1- Pancreatic adenocarcinoma 0.0
(liver metastasis)
SU86.86- Pancreatic carcinoma (liver metastasis) 0.1
BxPC-3- Pancreatic adenocarcinoma 1.5
HPAC- Pancreatic adenocarcinoma  0.0
MIA PaCa-2- Pancreatic carcinoma 1.4
CFPAC-1- Pancreatic ductal adenocarcinoma 1.4
PANC-1- Pancreatic epithelioid ductal carcinoma 4.6
T24- Bladder carcinma (transitional cell) 0.0
5637- Bladder carcinoma          0.0
HT-1197- Bladder carcinoma       0.0
UM-UC-3- Bladder carcinma (transitional cell) 0.0
A204- Rhabdomyosarcoma           3.5
HT-1080- Fibrosarcoma            0.0
MG-63- Osteosarcoma              0.0
SK-LMS-1- Leiomyosarcoma (vulva) 0.0
SJRH30- Rhabdomyosarcoma (met to bone marrow) 0.0
A431- Epidermoid carcinoma       0.0
WM266-4- Melanoma                4.9
DU 145- Prostate carcinoma (brain metastasis) 0.0
MDA-MB-468- Breast adenocarcinoma 4.1
SCC-4- Squamous cell carcinoma of tongue 0.0
SCC-9- Squamous cell carcinoma of tongue 0.0
SCC-15- Squamous cell carcinoma of tongue 0.0
CAL 27- Squamous cell carcinoma of tongue 0.0
Column A - Rel. Exp. (%) Ag2256, Run 170745682

[0700]

TABLE GH
Panel 4.1D
	Tissue Name	A	B
	Secondary Th1 act	0.0	1.5
	Secondary Th2 act	12.1	1.5
	Secondary Tr1 act	0.0	2.5
	Secondary Th1 rest	0.0	0.0
	Secondary Th2 rest	0.0	0.0
	Secondary Tr1 rest	0.0	0.0
	Primary Th1 act	0.0	7.1
	Primary Th2 act	0.0	7.1
	Primary Tr1 act	0.0	3.5
	Primary Th1 rest	0.0	0.8
	Primary Th2 rest	0.0	0.0
	Primary Tr1 rest	0.0	0.0
	CD45RA CD4 lymphocyte act	9.1	0.0
	CD45RO CD4 lymphocyte act	0.0	0.0
	CD8 lymphocyte act	0.0	0.0
	Secondary CD8 lymphocyte rest	0.0	1.4
	Secondary CD8 lymphocyte act	15.5	2.3
	CD4 lymphocyte none	0.0	0.0
	2ry Th1/Th2/Tr1_anti-CD95 CH11	0.0	0.0
	LAK cells rest	0.0	1.3
	LAK cells IL-2	0.0	0.0
	LAK cells IL-2 + IL-12	0.0	0.0
	LAK cells IL-2 + IFN gamma	0.0	0.0
	LAK cells IL-2 + IL-18	0.0	0.0
	LAK cells PMA/ionomycin	12.9	0.0
	NK Cells IL-2 rest	0.0	0.0
	Two Way MLR 3 day	0.0	0.0
	Two Way MLR 5 day	0.0	0.0
	Two Way MLR 7 day	0.0	1.9
	PBMC rest	0.0	0.0
	PBMC PWM	0.0	1.5
	PBMC PHA-L	15.4	0.0
	Ramos (B cell) none	0.0	0.0
	Ramos (B cell) ionomycin	0.0	0.0
	B lymphocytes PWM	0.0	1.6
	B lymphocytes CD40L and IL-4	13.0	0.9
	EOL-1 dbcAMP	12.2	0.0
	EOL-1 dbcAMP PMA/ionomycin	0.0	0.0
	Dendritic cells none	0.0	0.0
	Dendritic cells LPS	0.0	0.0
	Dendritic cells anti-CD40	0.0	0.0
	Monocytes rest	0.0	0.0
	Monocytes LPS	27.0	0.0
	Macrophages rest	0.0	0.0
	Macrophages LPS	0.0	1.6
	HUVEC none	0.0	0.0
	HUVEC starved	16.3	1.7
	HUVEC IL-1beta	16.7	0.4
	HUVEC IFN gamma	0.0	1.6
	HUVEC TNF alpha + IFN gamma	0.0	1.9
	HUVEC TNF alpha + IL4	18.6	0.0
	HUVEC IL-11	0.0	1.0
	Lung Micro vascular EC none	100.0	13.4
	Lung Microvascular EC TNFalpha +	15.8	3.4
	IL-1beta
	Microvascular Dermal EC none	0.0	0.7
	Microsvasular Dermal EC TNFalpha +	0.0	4.8
	IL-1beta
	Bronchial epithelium TNFalpha +	0.0	0.0
	IL1beta
	Small airway epithelium none	0.0	0.0
	Small airway epithelium TNFalpha +	0.0	0.0
	IL-1beta
	Coronery artery SMC rest	26.4	0.0
	Coronery artery SMC TNFalpha + IL-	29.1	0.0
	1beta
	Astrocytes rest	4.7	0.0
	Astrocytes TNFalpha + IL-1beta	44.1	2.7
	KU-812 (Basophil) rest	0.0	0.0
	KU-812 (Basophil) PMA/ionomycin	0.0	0.9
	CCD1106 (Keratinocytes) none	0.0	0.0
	CCD1106 (Keratinocytes) TNFalpha +	0.0	4.6
	IL-1beta
	Liver cirrhosis	0.0	0.5
	NCI-H292 none	0.0	1.5
	NCI-H292 IL-4	0.0	0.0
	NCI-H292 IL-9	0.0	0.0
	NCI-H292 IL-13	0.0	0.0
	NCI-H292 IFN gamma	14.2	0.0
	HPAEC none	0.0	0.0
	HPAEC TNF alpha + IL-1 beta	6.8	0.0
	Lung fibroblast none	6.3	0.7
	Lung fibroblast TNF alpha + IL-1 beta	0.0	1.5
	Lung fibroblast IL-4	0.0	3.3
	Lung fibroblast IL-9	0.0	4.4
	Lung fibroblast IL-13	0.0	4.2
	Lung fibroblast IFN gamma	0.0	2.6
	Dermal fibroblast CCD1070 rest	16.3	1.7
	Dermal fibroblast CCD1070 TNF alpha	11.7	0.0
	Dermal fibroblast CCD1070 IL-1 beta	21.5	3.6
	Dermal fibroblast IFN gamma	0.0	0.0
	Dermal fibroblast IL-4	0.0	3.8
	Dermal Fibroblasts rest	0.0	3.4
	Neutrophils TNFa + LPS	0.0	4.8
	Neutrophils rest	0.0	3.4
	Colon	35.6	3.8
	Lung	0.0	6.3
	Thymus	0.0	38.4
	Kidney	0.0	100.0
	Column A - Rel. Exp. (%) Ag2256, Run 296422901
	Column B - Rel. Exp. (%) Ag4933, Run 223597253

[0701] General_screening_panel_v1.5 Summary: Highest expression of this gene is detected in NCI-H146 lung cancer cell line (CTs=30). Other lung as well as colon and ovarian cancer cell lines express this gene. Gene expression and/or detection of the gene product can then be used to differenctiate these cell lines from others or to detect these cancer cells in tissue specimens. Moreover, therapeutic modulation of this gene, through the use of, for example, small molecule drugs, protein therapeutics or antibodies will be of benefit in the treatment of lung cancer, colon cancer or ovarian cancer.

[0702] This gene also has moderate expression in adipose, adult and fetal skeletal muscle, and pituitary, therefore the gene or its product will be a target for modulation for the treatment of metabolic and endocrine disease, including obesity and Types 1 and 2 diabetes.

[0703] In addition, this gene is expressed at low levels in all CNS regions examined. This gene is a homolog of Frizzled which plays a role in determining cell fate (Moriwaki J, Kajita E, Kirikoshi H, Koike J, Sagara N, Yasuhiko Y, Saitoh T, Hirai M, Katoh M, Shiokawa K. Isolation of Xenopus frizzled-10A and frizzled-10B genomic clones and their expression in adult tissues and embryos. Biochem Biophys Res Commun Nov. 19, 2000; 278(2):377-84). Therefore, this gene will be of use in stem cell research and therapy for example, to control the differentiation of stem cells into post-mitotic neurons.

[0704] HASS Panel v1.0 Summary: Ag2256 Expression of this gene is highest in a glioma sample (CT=30.73). as well as. Expression is also seen at low level in medulloblastoma, LnCAP and MCF-7 cell lines and is induced by a low oxygen tension in LnCAP.

[0705] Modulation of this gene or its product, for example through the use of small molecules, antibodies or protein therapeutics can be used in treating cancer.

[0706] Panel 1.3D Summary: Highest expression of this gene is detected in fetal skeletal muscle (CTs=31-33), higher than in adult skeletal muscle (CTs=36-37). The higher levels of expression in fetal skeletal muscle suggests that the protein product may enhance muscular growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of muscle related diseases. This panel also shows expression of this gene in the CNS.

[0707] Panel 2D Summary: Ag2256 The expression of this gene is highest in a lung cancer specimen (CTs=30). Other lung cancers express this gene, while the matched normal tissue showed low to undetectable expression levels. Thus, the expression of this gene could be used to detect lung cancer from normal adjacent lung tissue. Moreover, therapeutic modulation of this gene, for example, through the use of small molecule drugs, antibodies or protein therapeutics can be beneficial in the treatment of lung cancer.

[0708] Panel 3D Summary: Ag2256 Highest gene expression is detected in NCI-H146 lung cancer cell line (CT=30), with significant expression detected in other lung cancer cell lines

[0709] Panel 4.1D Summary: Ag4933 This gene is expressed at moderate levels in kidney (CT=31.31) and thymus (CT=32.69) and at low levels in colon (CT=33.55) and lung (CT=34.7). Therefore, antibodies or small molecule antagonists that block the function of the CG55690-01 product will be useful to reduce or eliminate the symptoms in patients with diseases of kidney, thymus, colon, and lung.

H. NOV 8, CG57049-01: Phosphatidylethanolamine-Binding Protein

[0710] Expression of gene CG57049-01 was assessed using the primer-probe sets Ag2678 and Ag36, described in Tables HA and HB. Results of the RTQ-PCR runs are shown in Tables HC, HD, HE, HF, HG, HH. CG57049-01 is a full length physical clone.

TABLE HA
Probe Name Ag2678
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-cgcaacctatatcctggtgat-3′	21	489	219
Probe	TET-5′-atccagatgcccctagcagagcagaa-3′-	26	458	220
	TAMRA
Reverse	5′-agccaatgtctccagaatctct-3′	22	429	221

[0711]

TABLE HB
Probe Name Ag36
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-caggtggaaacggttcagaaa-3′	21	212	222
Probe	TET-5′-ctgtccattttccaagagcctcgagttttgt-	31	234	223
	3′-TAMRA
Reverse	5′-catctctctccttcccaaggaa-3′	22	266	224

[0712]

TABLE HC
Panel 1
Tissue Name                      A
Endothelial cells                0.0
Endothelial cells (treated)      0.0
Pancreas                         2.0
Pancreatic ca. CAPAN 2           0.0
Adrenal gland                    0.9
Thyroid                          21.2
Salivary gland                   7.6
Pituitary gland                  0.1
Brain (fetal)                    0.2
Brain (whole)                    2.0
Brain (amygdala)                 1.0
Brain (cerebellum)               4.6
Brain (hippocampus)              3.0
Brain (substantia nigra)         6.3
Brain (thalamus)                 4.8
Brain (hypothalamus)             10.5
Spinal cord                      1.8
glio/astro U87-MG                0.0
glio/astro U-118-MG              0.0
astrocytoma SW1783               0.0
neuro*; met SK-N-AS              0.0
astrocytoma SF-539               0.1
astrocytoma SNB-75               0.0
glioma SNB-19                    0.0
glioma U251                      0.0
glioma SF-295                    0.0
Heart                            33.9
Skeletal muscle                  100.0
Bone marrow                      1.0
Thymus                           0.3
Spleen                           0.1
Lymph node                       0.3
Colon (ascending)                0.0
Stomach                          0.6
Small intestine                  0.1
Colon ca. SW480                  0.0
Colon ca.* SW620 (SW480 met)     0.0
Colon ca. HT29                   0.0
Colon ca. HCT-116                0.0
Colon ca. CaCo-2                 0.0
Colon ca. HCT-15                 0.0
Colon ca. HCC-2998               0.0
Gastric ca. * (liver met) NCI-N87 0.0
Bladder                          0.2
Trachea                          1.2
Kidney                           0.4
Kidney (fetal)                   0.3
Renal ca. 786-0                  0.0
Renal ca. A498                   0.0
Renal ca. RXF 393                0.0
Renal ca. ACHN                   0.0
Renal ca. UO-31                  0.0
Renal ca. TK-10                  0.0
Liver                            0.1
Liver (fetal)                    0.0
Liver ca. (hepatoblast) HepG2    0.0
Lung                             6.2
Lung (fetal)                     7.1
Lung ca. (small cell) LX-1       0.0
Lung ca. (small cell) NCI-H69    0.0
Lung ca. (s. cell var.) SHP-77   0.0
Lung ca. (large cell)NCI-H460    0.0
Lung ca. (non-sm. cell) A549     0.0
Lung ca. (non-s. cell) NCI-H23   0.0
Lung ca. (non-s. cell) HOP-62    0.0
Lung ca. (non-s. cl) NCI-H522    0.0
Lung ca. (squam.) SW 900         0.0
Lung ca. (squam.) NCI-H596       0.1
Mammary gland                    0.5
Breast ca.* (pl. ef) MCF-7       0.0
Breast ca.* (pl. ef) MDA-MB-231  0.0
Breast ca.* (pl. ef) T47D        0.0
Breast ca. BT-549                0.0
Breast ca. MDA-N                 0.0
Ovary                            0.1
Ovarian ca. OVCAR-3              0.0
Ovarian ca. OVCAR-4              0.0
Ovarian ca. OVCAR-5              0.0
Ovarian ca. OVCAR-8              0.0
Ovarian ca. IGROV-1              0.0
Ovarian ca. (ascites) SK-OV-3    0.0
Uterus                           0.5
Placenta                         0.2
Prostate                         15.0
Prostate ca.* (bone met) PC-3    0.0
Testis                           8.7
Melanoma Hs688(A).T              0.0
Melanoma* (met) Hs688(B).T       0.0
Melanoma UACC-62                 0.0
Melanoma M14                     0.0
Melanoma LOX IMVI                0.0
Melanoma* (met) SK-MEL-5         0.0
Melanoma SK-MEL-28               0.0
Column A - Rel. Exp. (%) Ag36, Run 87587974

[0713]

TABLE HD
Panel 1.3D
	Tissue Name	A	B
	Liver adenocarcinoma	0.0	0.0
	Pancreas	0.8	0.2
	Pancreatic ca. CAPAN 2	0.0	0.0
	Adrenal gland	0.2	0.2
	Thyroid	22.7	6.8
	Salivary gland	3.9	1.0
	Pituitary gland	3.6	0.5
	Brain (fetal)	0.1	0.1
	Brain (whole)	1.4	0.5
	Brain (amygdala)	1.0	0.5
	Brain (cerebellum)	0.9	0.6
	Brain (hippocampus)	7.9	0.9
	Brain (substantia nigra)	3.8	1.4
	Brain (thalamus)	6.0	2.2
	Cerebral Cortex	7.2	6.2
	Spinal cord	1.1	1.7
	glio/astro U87-MG	0.0	0.0
	glio/astro U-118-MG	0.1	0.0
	astrocytoma SW1783	0.0	0.0
	neuro*; met SK-N-AS	0.0	0.0
	astrocytoma SF-539	0.2	0.1
	astrocytoma SNB-75	0.1	0.0
	glioma SNB-19	0.0	0.0
	glioma U251	0.0	0.0
	glioma SF-295	0.0	0.0
	Heart (fetal)	8.1	7.4
	Heart	21.2	27.7
	Skeletal muscle (fetal)	100.0	85.3
	Skeletal muscle	51.4	100.0
	Bone marrow	0.5	0.1
	Thymus	0.2	0.3
	Spleen	0.2	0.0
	Lymph node	0.3	0.0
	Colorectal	0.2	0.1
	Stomach	1.5	0.3
	Small intestine	0.1	0.0
	Colon ca. SW480	0.0	0.0
	Colon ca.* SW620(SW480 met)	0.0	0.0
	Colon ca. HT29	0.0	0.0
	Colon ca. HCT-116	0.0	0.0
	Colon ca. CaCo-2	0.0	0.0
	Colon ca. tissue(ODO3866)	0.1	0.0
	Colon ca. HCC-2998	0.0	0.0
	Gastric ca.* (liver met) NCI-N87	0.0	0.0
	Bladder	0.0	0.0
	Trachea	4.8	1.7
	Kidney	0.2	0.2
	Kidney (fetal)	0.1	0.0
	Renal ca. 786-0	0.0	0.0
	Renal ca. A498	0.0	0.0
	Renal ca. RXF 393	0.0	0.0
	Renal ca. ACHN	0.0	0.0
	Renal ca. UO-31	0.0	0.0
	Renal ca. TK-10	0.0	0.0
	Liver	1.0	0.2
	Liver (fetal)	0.0	0.0
	Liver ca. (hepatoblast) HepG2	0.0	0.0
	Lung	59.9	12.8
	Lung (fetal)	11.0	5.8
	Lung ca. (small cell) LX-1	0.1	0.0
	Lung ca. (small cell) NCI-H69	0.0	0.0
	Lung ca. (s. cell var.) SHP-77	0.0	0.0
	Lung ca. (large cell)NCI-H460	0.0	0.0
	Lung ca. (non-sm. cell) A549	0.0	0.0
	Lung ca. (non-s. cell) NCI-H23	0.0	0.0
	Lung ca. (non-s. cell) HOP-62	0.0	0.0
	Lung ca. (non-s. cl) NCI-H522	0.0	0.0
	Lung ca. (squam.) SW 900	0.0	0.0
	Lung ca. (squam.) NCI-H596	0.0	0.0
	Mammary gland	1.0	0.3
	Breast ca.* (pl. ef) MCF-7	0.0	0.0
	Breast ca.* (pl. ef) MDA-MB-231	0.0	0.0
	Breast ca.* (pl. ef) T47D	0.0	0.0
	Breast ca. BT-549	0.1	0.0
	Breast ca. MDA-N	0.0	0.0
	Ovary	0.8	0.6
	Ovarian ca. OVCAR-3	0.0	0.0
	Ovarian ca. OVCAR-4	0.0	0.0
	Ovarian ca. OVCAR-5	0.1	0.0
	Ovarian ca. OVCAR-8	0.0	0.1
	Ovarian ca. IGROV-1	0.0	0.0
	Ovarian ca.* (ascites) SK-OV-3	0.0	0.0
	Uterus	0.0	0.0
	Placenta	0.4	0.0
	Prostate	8.2	4.6
	Prostate ca.* (bone met)PC-3	0.0	0.0
	Testis	6.1	2.0
	Melanoma Hs688(A).T	0.0	0.0
	Melanoma* (met) Hs688(B).T	0.0	0.0
	Melanoma UACC-62	0.0	0.0
	Melanoma M14	0.0	0.0
	Melanoma LOX IMVI	0.0	0.0
	Melanoma* (met) SK-MEL-5	0.0	0.0
	Adipose	1.2	0.6
	Column A - Rel. Exp. (%) Ag2678, Run 158535212
	Column B - Rel. Exp. (%) Ag36, Run 161682677

[0714]

TABLE HE
Panel 2D
Tissue Name	A	B
Normal Colon	6.5	5.3
CC Well to Mod Diff (ODO3866)	0.1	0.0
CC Margin (ODO3866)	0.1	0.1
CC Gr.2 rectosigmoid (ODO3868)	0.0	0.0
CC Margin (ODO3868)	0.1	0.1
CC Mod Diff (ODO3920)	0.0	0.0
CC Margin (ODO3920)	0.0	0.1
CC Gr.2 ascend colon (ODO3921)	0.0	0.0
CC Margin (ODO3921)	0.0	0.0
CC from Partial Hepatectomy (ODO4309) Mets	0.1	0.2
Liver Margin (ODO4309)	0.5	0.3
Colon mets to lung (OD04451-01)	10.4	14.0
Lung Margin (OD04451-02)	36.6	50.0
Normal Prostate 6546-1	13.1	13.6
Prostate Cancer (OD04410)	4.9	6.5
Prostate Margin (OD04410)	13.6	26.8
Prostate Cancer (OD04720-01)	11.4	18.9
Prostate Margin (OD04720-02)	30.4	38.7
Normal Lung 061010	35.8	46.0
Lung Met to Muscle (ODO4286)	0.0	0.0
Muscle Margin (ODO4286)	54.3	55.5
Lung Malignant Cancer (OD03126)	11.7	14.9
Lung Margin (OD03126)	92.7	100.0
Lung Cancer (OD04404)	7.7	12.5
Lung Margin (OD04404)	22.5	29.5
Lung Cancer (OD04565)	0.1	0.1
Lung Margin (OD04565)	18.9	29.1
Lung Cancer (OD04237-01)	1.1	1.1
Lung Margin (OD04237-02)	29.9	27.0
Ocular Mel Met to Liver (ODO4310)	0.0	0.1
Liver Margin (ODO4310)	0.2	0.1
Melanoma Mets to Lung (OD04321)	0.5	0.4
Lung Margin (OD04321)	100.0	92.0
Normal Kidney	0.7	0.7
Kidney Ca, Nuclear grade 2 (OD04338)	0.7	0.3
Kidney Margin (OD04338)	1.4	0.8
Kidney Ca Nuclear grade 1/2 (OD04339)	0.1	0.0
Kidney Margin (OD04339)	0.6	1.4
Kidney Ca, Clear cell type (OD04340)	0.3	0.3
Kidney Margin (OD04340)	1.2	0.7
Kidney Ca, Nuclear grade 3 (OD04348)	0.0	0.2
Kidney Margin (OD04348)	0.3	0.4
Kidney Cancer (OD04622-01)	0.3	0.1
Kidney Margin (OD04622-03)	0.0	0.2
Kidney Cancer (OD04450-01)	0.0	0.0
Kidney Margin (OD04450-03)	1.0	0.6
Kidney Cancer 8120607	0.2	0.0
Kidney Margin 8120608	0.3	0.4
Kidney Cancer 8120613	0.1	0.0
Kidney Margin 8120614	1.5	1.4
Kidney Cancer 9010320	0.1	0.1
Kidney Margin 9010321	1.1	0.8
Normal Uterus	0.2	0.1
Uterus Cancer 064011	0.3	0.4
Normal Thyroid	22.1	23.5
Thyroid Cancer 064010	6.6	10.3
Thyroid Cancer A302152	14.1	20.9
Thyroid Margin A302153	24.3	18.6
Normal Breast	1.2	0.3
Breast Cancer (OD04566)	0.0	0.1
Breast Cancer (OD04590-01)	3.1	2.5
Breast Cancer Mets (OD04590-03)	0.3	0.3
Breast Cancer Metastasis (OD04655-05)	0.3	0.2
Breast Cancer 064006	0.2	0.3
Breast Cancer 1024	1.4	0.8
Breast Cancer 9100266	0.2	0.1
Breast Margin 9100265	0.7	0.4
Breast Cancer A209073	0.3	0.4
Breast Margin A209073	0.7	0.9
Normal Liver	0.0	0.0
Liver Cancer 064003	0.0	0.0
Liver Cancer 1025	0.0	0.2
Liver Cancer 1026	0.1	0.0
Liver Cancer 6004-T	0.1	0.1
Liver Tissue 6004-N	0.0	0.0
Liver Cancer 6005-T	0.1	0.1
Liver Tissue 6005-N	0.1	0.0
Normal Bladder	0.1	0.1
Bladder Cancer 1023	0.1	0.2
Bladder Cancer A302173	0.0	0.1
Bladder Cancer (OD04718-01)	0.1	0.1
Bladder Normal Adjacent (OD04718-03)	0.0	0.0
Normal Ovary	0.3	0.1
Ovarian Cancer 064008	0.4	0.1
Ovarian Cancer (OD04768-07)	0.0	0.0
Ovary Margin (OD04768-08)	0.1	0.0
Normal Stomach	0.5	0.7
Gastric Cancer 9060358	0.2	0.3
Stomach Margin 9060359	1.2	1.1
Gastric Cancer 9060395	0.2	0.2
Stomach Margin 9060394	0.8	0.8
Gastric Cancer 9060397	0.2	0.1
Stomach Margin 9060396	0.3	0.5
Gastric Cancer 064005	0.0	0.1
Column A - Rel. Exp. (%) Ag2678, Run 158536099
Column B - Rel. Exp. (%) Ag36, Run 161680686

[0715]

TABLE HF
Panel 3D
Tissue Name                      A
Daoy- Medulloblastoma            4.1
TE671- Medulloblastoma           0.0
D283 Med- Medulloblastoma        0.0
PFSK-1- Primitive Neuroectodermal 2.7
XF-498- CNS                      0.0
SNB-78- Glioma                   0.0
SF-268- Glioblastoma             0.0
T98G- Glioblastoma               0.7
SK-N-SH- Neuroblastoma (metastasis) 0.0
SF-295- Glioblastoma             1.4
Cerebellum                       100.0
Cerebellum                       98.6
NCI-H292- Mucoepidermoid lung carcinoma 1.2
DMS-114- Small cell lung cancer  0.6
DMS-79- Small cell lung cancer   1.4
NCI-H146- Small cell lung cancer 0.0
NCI-H526- Small cell lung cancer 0.0
NCI-N417- Small cell lung cancer 0.0
NCI-H82- Small cell lung cancer  0.0
NCI-H157- Squamous cell lung cancer (metastasis) 0.0
NCI-H1155- Large cell lung cancer 0.0
NCI-H1299- Large cell lung cancer 0.0
NCI-H727- Lung carcinoid         0.6
NCI-UMC-11- Lung carcinoid       0.0
LX-1- Small cell lung cancer     0.0
Colo-205- Colon cancer           0.0
KM12- Colon cancer               0.8
KM20L2- Colon cancer             0.0
NCI-H716- Colon cancer           0.0
SW-48- Colon adenocarcinoma      0.0
SW1116- Colon adenocarcinoma     0.0
LS 174T- Colon adenocarcinoma    0.0
SW-948- Colon adenocarcinoma     0.0
SW-480- Colon adenocarcinoma     0.0
NCI-SNU-5- Gastric carcinoma     0.0
KATO III- Gastric carcinoma      0.0
NCI-SNU-16- Gastric carcinoma    0.0
NCI-SNU-1- Gastric carcinoma     0.0
RF-1- Gastric adenocarcinoma     0.6
RF-48- Gastric adenocarcinoma    0.0
MKN-45- Gastric carcinoma        0.0
NCI-N87- Gastric carcinoma       0.0
OVCAR-5- Ovarian carcinoma       0.0
RL95-2- Uterine carcinoma        0.0
HelaS3- Cervical adenocarcinoma  0.0
Ca Ski- Cervical epidermoid carcinoma (metastasis) 0.0
ES-2- Ovarian clear cell carcinoma 0.0
Ramos- Stimulated with PMA/ionomycin 6 h 0.0
Ramos- Stimulated with PMA/ionomycin 14 h 0.0
MEG-01- Chronic myelogenous leukemia 0.0
(megokaryoblast)
Raji- Burkitt's lymphoma         0.0
Daudi- Burkitt's lymphoma        3.4
U266- B-cell plasmacytoma        0.8
CA46- Burkitt's lymphoma         0.7
RL- non-Hodgkin's B-cell lymphoma 0.0
JM1- pre-B-cell lymphoma         0.0
Jurkat- T cell leukemia          0.0
TF-1- Erythroleukemia            0.0
HUT 78- T-cell lymphoma          0.0
U937- Histiocytic lymphoma       1.8
KU-812- Myelogenous leukemia     0.0
769-P- Clear cell renal carcinoma 0.0
Caki-2- Clear cell renal carcinoma 0.0
SW 839- Clear cell renal carcinoma 0.0
Rhabdoid kidney tumor            0.0
Hs766T- Pancreatic carcinoma (LN metastasis) 1.3
CAPAN-1- Pancreatic adenocarcinoma (liver 0.0
metastasis)
SU86.86- Pancreatic carcinoma (liver metastasis) 0.0
BxPC-3- Pancreatic adenocarcinoma 0.3
HPAC- Pancreatic adenocarcinoma  0.0
MIA PaCa-2- Pancreatic carcinoma 0.0
CFPAC-1- Pancreatic ductal adenocarcinoma 0.8
PANC-1- Pancreatic epithelioid ductal carcinoma 0.0
T24- Bladder carcinma (transitional cell) 0.0
5637- Bladder carcinoma          0.0
HT-1197- Bladder carcinoma       2.6
UM-UC-3- Bladder carcinma (transitional cell) 0.0
A204- Rhabdomyosarcoma           0.0
HT-1080- Fibrosarcoma            0.0
MG-63- Osteosarcoma              1.5
SK-LMS-1- Leiomyosarcoma (vulva) 0.0
SJRH30- Rhabdomyosarcoma (met to bone marrow) 0.0
A431- Epidermoid carcinoma       0.0
WM266-4- Melanoma                0.0
DU 145- Prostate carcinoma (brain metastasis) 0.0
MDA-MB-468- Breast adenocarcinoma 0.0
SCC-4- Squamous cell carcinoma of tongue 0.0
SCC-9- Squamous cell carcinoma of tongue 0.0
SCC-15- Squamous cell carcinoma of tongue 0.0
CAL 27- Squamous cell carcinoma of tongue 0.0
Column A - Rel. Exp. (%) Ag36, Run 161682678

[0716]

TABLE HG
Panel 4D
	Tissue Name	A	B
	Secondary Th1 act	0.0	0.0
	Secondary Th2 act	0.0	0.0
	Secondary Tr1 act	0.0	0.0
	Secondary Th1 rest	0.0	0.0
	Secondary Th2 rest	0.0	0.0
	Secondary Tr1 rest	0.2	0.2
	Primary Th1 act	0.0	0.0
	Primary Th2 act	0.0	0.0
	Primary Tr1 act	0.0	0.0
	Primary Th1 rest	0.0	0.0
	Primary Th2 rest	0.0	0.1
	Primary Tr1 rest	0.3	0.1
	CD45RA CD4 lymphocyte act	0.2	0.0
	CD45RO CD4 lymphocyte act	0.0	0.0
	CD8 lymphocyte act	0.0	0.0
	Secondary CD8 lymphocyte rest	0.0	0.0
	Secondary CD8 lymphocyte act	0.0	0.0
	CD4 lymphocyte none	0.0	0.0
	2ry Th1/Th2/Tr1_anti-CD95 CH11	0.0	0.0
	LAK cells rest	0.0	0.0
	LAK cells IL-2	0.2	0.0
	LAK cells IL-2 + IL-12	0.0	0.0
	LAK cells IL-2 + IFN gamma	0.0	0.0
	LAK cells IL-2 + IL-18	0.4	0.0
	LAK cells PMA/ionomycin	0.1	0.0
	NK Cells IL-2 rest	0.0	0.0
	Two Way MLR 3 day	0.2	0.0
	Two Way MLR 5 day	0.0	0.0
	Two Way MLR 7 day	0.0	0.0
	PBMC rest	0.0	0.0
	PBMC PWM	0.0	0.0
	PBMC PHA-L	0.0	0.0
	Ramos (B cell) none	0.0	0.0
	Ramos (B cell) ionomycin	0.7	0.1
	B lymphocytes PWM	0.0	0.0
	B lymphocytes CD40L and IL-4	0.9	0.5
	EOL-1 dbcAMP	0.0	0.0
	EOL-1 dbcAMP PMA/ionomycin	0.1	0.0
	Dendritic cells none	0.0	0.0
	Dendritic cells LPS	0.4	0.3
	Dendritic cells anti-CD40	0.2	0.0
	Monocytes rest	0.0	0.0
	Monocytes LPS	0.0	0.0
	Macrophages rest	0.6	0.9
	Macrophages LPS	0.0	0.1
	HUVEC none	0.0	0.0
	HUVEC starved	0.0	0.0
	HUVEC IL-1beta	0.0	0.0
	HUVEC IFN gamma	0.0	0.0
	HUVEC TNF alpha + IFN gamma	0.0	0.0
	HUVEC TNF alpha + IL4	0.0	0.0
	HUVEC IL-11	0.0	0.0
	Lung Microvascular EC none	0.0	0.1
	Lung Microvascular EC TNFalpha +	0.0	0.1
	IL-1beta
	Microvascular Dermal EC none	0.0	0.0
	Microsvasular Dermal EC TNFalpha +	0.0	0.0
	IL-1beta
	Bronchial epithelium TNFalpha +	0.2	0.0
	IL1beta
	Small airway epithelium none	0.0	0.0
	Small airway epithelium TNFalpha +	0.0	0.1
	IL-1beta
	Coronery artery SMC rest	0.0	0.0
	Coronery artery SMC TNFalpha + IL-	0.0	0.0
	1beta
	Astrocytes rest	0.0	0.0
	Astrocytes TNFalpha + IL-1beta	0.3	0.0
	KU-812 (Basophil) rest	0.0	0.0
	KU-812 (Basophil) PMA/ionomycin	0.0	0.0
	CCD1106 (Keratinocytes) none	0.0	0.0
	CCD1106 (Keratinocytes) TNFalpha +	0.0	0.0
	IL-1beta
	Liver cirrhosis	1.4	0.0
	Lupus kidney	0.0	0.1
	NCI-H292 none	2.4	1.8
	NCI-H292 IL-4	2.2	1.8
	NCI-H292 IL-9	3.2	0.7
	NCI-H292 IL-13	2.4	0.3
	NCI-H292 IFN gamma	0.8	0.1
	HPAEC none	0.0	0.0
	HPAEC TNF alpha + IL-1 beta	0.0	0.0
	Lung fibroblast none	0.2	0.0
	Lung fibroblast TNF alpha + IL-1 beta	0.7	0.0
	Lung fibroblast IL-4	1.1	0.3
	Lung fibroblast IL-9	0.4	0.4
	Lung fibroblast IL-13	0.2	0.3
	Lung fibroblast IFN gamma	0.4	0.1
	Dermal fibroblast CCD1070 rest	0.2	0.2
	Dermal fibroblast CCD1070 TNF alpha	0.0	0.0
	Dermal fibroblast CCD1070 IL-1 beta	0.0	0.6
	Dermal fibroblast IFN gamma	0.0	0.3
	Dermal fibroblast IL-4	0.2	0.0
	IBD Colitis 2	0.0	0.0
	IBD Crohn's	0.1	0.1
	Colon	1.5	0.2
	Lung	100.0	100.0
	Thymus	1.9	3.2
	Kidney	2.5	2.1
	Column A - Rel. Exp. (%) Ag2678, Run 158536138
	Column B - Rel. Exp. (%) Ag36, Run 161681141

[0717]

TABLE HH
Panel 5D
Tissue Name                      A
97457_Patient-02go_adipose       0.3
97476_Patient-07sk_skeletal muscle 5.0
97477_Patient-07ut_uterus        0.2
97478_Patient-07pl_placenta      0.4
97481_Patient-08sk_skeletal muscle 11.1
97482_Patient-08ut_uterus        0.0
97483_Patient-08pl_placenta      0.1
97486_Patient-09sk_skeletal muscle 14.5
97487_Patient-09ut_uterus        0.1
97488_Patient-09pl_placenta      0.3
97492_Patient-10ut_uterus        0.3
97493_Patient-10pl_placenta      0.2
97495_Patient-11go_adipose       0.1
97496_Patient-11sk_skeletal muscle 36.9
97497_Patient-11ut_uterus        0.1
97498_Patient-11pl_placenta      0.2
97500_Patient-12go_adipose       0.1
97501_Patient-12sk_skeletal muscle 100.0
97502_Patient-12ut_uterus        0.1
97503_Patient-12pl_placenta      0.0
94721_Donor 2 U - A_Mesenchymal Stem Cells 0.0
94722_Donor 2 U - B_Mesenchymal Stem Cells 0.1
94723_Donor 2 U - C_Mesenchymal Stem Cells 0.0
94709_Donor 2 AM - A_adipose     0.3
94710_Donor 2 AM - B_adipose     0.4
94711_Donor 2 AM - C_adipose     0.1
94712_Donor 2 AD - A_adipose     0.1
94713_Donor 2 AD - B_adipose     0.2
94714_Donor 2 AD - C_adipose     0.2
94742_Donor 3 U - A_Mesenchymal Stem Cells 0.0
94743_Donor 3 U - B_Mesenchymal Stem Cells 0.0
94730_Donor 3 AM - A_adipose     0.1
94731_Donor 3 AM - B_adipose     0.0
94732_Donor 3 AM - C_adipose     0.0
94733_Donor 3 AD - A_adipose     26.8
94734_Donor 3 AD - B_adipose     0.0
94735_Donor 3 AD - C_adipose     0.0
77138_Liver_HepG2untreated       0.0
73556_Heart_Cardiac stromal cells (primary) 0.1
81735_Small_Intestine            1.1
72409_Kidney_Proximal Convoluted Tubule 0.1
82685_Small intestine_Duodenum   0.0
90650_Adrenal_Adrenocortical adenoma 0.0
72410_Kidney_HRCE                0.1
72411_Kidney_HRE                 0.0
73139_Uterus_Uterine smooth muscle cells 0.0
Column A - Rel. Exp. (%) Ag36, Run 169315041

[0718] Panel 1 Summary: Ag36 Highest expression of this gene is seen in skeletal muscle (CT=23.8).

[0719] Panel 1.3D Summary: Ag2678/Ag36 Highest expression of this gene is seen in fetal and adult skeletal muscle (CTs=25), therefore, therapeutic modulation of gene expression or its protein product will be useful in the treatment of muscle related diseases. Significant expression is detected in metabolic/endocrine tissues including adipose, pancreas, thyroid, adrenal gland, pituitary gland, heart, liver and gastrointestinal tract. Therefore, therapeutic modulation of the activity of this gene will prove useful in the treatment of endocrine/metabolically related diseases, such as obesity and diabetes.

[0720] Moderate expression of this gene is seen in all central nervous system tissues examined including amygdala, hippocampus, substantia nigra, thalamus, cerebellum, cerebral cortex, and spinal cord. Therefore, therapeutic modulation of this gene product will be useful in the treatment of central nervous system disorders such as Alzheimer's disease, Parkinson's disease, epilepsy, multiple sclerosis, schizophrenia and depression.

[0721] Panel 2D Summary: Ag2678/Ag36 Highest expression of this gene is seen in normal lung margin samples (CTs=24.8-26). This gene shows moderate to low expression in normal and cancerous lung, stomach, breast, prostate, thyroid, kidney, and colon. Expression of this gene is higher in normal tissues than in cancer, therefore, therapeutic modulation of the activity of this gene or its protein product, for example, through the use of small molecule drugs, protein therapeutics or antibodies, will be beneficial in the treatment of lung, stomach, breast, prostate, thyroid, kidney, and colon cancers.

[0722] Panel 3D Summary: Ag36 Highest expression of this gene is seen in cerebellum (CTs=30). Therefore, therapeutic modulation of this gene or its protein product will be useful in the treatment of cerebellum related diseases such as ataxia and autism.

[0723] Panel 4D Summary: Ag2678/Ag36 Highest expression of this gene is seen in lung (CTs=27). Moderate to low expression of this gene is seen in resting and activated mucoepidermoid cell line NCI-H292, colon, thymus and kidney. Therapeutic modulation of this gene will be used for the treatment of inflammatory/autoimmune diseases that affect colon, lung and kidney including asthma, allergies, inflammatory bowel disease, lupus erythematosus, psoriasis, and emphysema.

[0724] Panel 5D Summary: Ag36 Highest expression of this gene is seen in skeletal muscle from a diabetic patient on insulin (patient 12)(CT=26.6). Significant expression is detected in skeletal muscle from non-diabetic but obese patients and also in adipose tissue. Therefore, therapeutic modulation of the activity of this gene or its protein product will be useful in the treatment of metabolic disease such as diabetes and obesity.

I. NOV 9, CG59538-01 and CG59538-02: Butyrophilin

[0725] Expression of gene CG59538-01 and CG59538-02 was assessed using the primer-probe sets Ag1849, Ag685, Ag887 and Ag6967, described in Tables IA, IB, IC and ID. Results of the RTQ-PCR runs are shown in Tables IE, IF, IG, IH, II, IJ, IK, IL, IM, IN and IO.

TABLE IA
Probe Name Ag1849
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-accaaagacacgatgcatagtc-3′	22	2041	225
Probe	TET-5′-ccttgtttctccaatggccgtgata-3′-	25	2070	226
	TAMRA
Reverse	5′-gggctgaacatgatcactagtg-3′	22	2095	227

[0726]

TABLE IB
Probe Name Ag685
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-tcctcacagctctgtttgatct-3′	22	1497	228
Probe	TET-5′-ttctccagcacacgaaagccagg-3′-	23	1474	229
	TAMRA
Reverse	5′-gggctgtctgtctgtctcatt-3′	21	1439	230

[0727]

TABLE IC
Probe Name Ag887
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-cctaacacagtgctgacatctg-3′	22	2537	231
Probe	TET-5′-tgctcaataaacatcaactgaatgga-3′-	26	2507	232
	TAMRA
Reverse	5′-ctgccttctcacctctttgtt-3′	21	2470	233

[0728]

TABLE ID
Probe Name Ag6967
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-gaagcatgtgctggtcaca-3′	19	2399	234
Probe	TET-5′-catcacagacccctggagaaccag-3′-	24	2418	235
	TAMRA
Reverse	5′-agaaaggaacaaagaggtgagaag-3′	24	2474	236

[0729]

TABLE IE
AI_comprehensive panel_v1.0
Column A - Rel. Exp. (%) Ag1849, Run 228175060
Tissue Name	A	Tissue Name	A
110967 COPD-F	37.6	112427 Match Control Psoriasis-F	53.2
110980 COPD-F	16.0	112418 Psoriasis-M	35.6
110968 COPD-M	36.9	112723 Match Control Psoriasis-M	72.7
110977 COPD-M	42.3	112419 Psoriasis-M	50.7
110989 Emphysema-F	69.7	112424 Match Control Psoriasis-M	2.7
110992 Emphysema-F	40.3	112420 Psoriasis-M	89.5
110993 Emphysema-F	42.6	112425 Match Control Psoriasis-M	39.2
110994 Emphysema-F	21.5	104689 (MF) OA Bone-Backus	71.2
110995 Emphysema-F	83.5	104690 (MF) Adj “Normal” Bone-Backus	19.2
110996 Emphysema-F	23.0	104691 (MF) OA Synovium-Backus	42.0
110997 Asthma-M	18.8	104692 (BA) OA Cartilage-Backus	47.6
111001 Asthma-F	35.4	104694 (BA) OA Bone-Backus	100.0
111002 Asthma-F	46.0	104695 (BA) Adj “Normal” Bone-Backus	31.0
111003 Atopic Asthma-F	48.6	104696 (BA) OA Synovium-Backus	52.1
111004 Atopic Asthma-F	90.8	104700 (SS) OA Bone-Backus	19.9
111005 Atopic Asthma-F	42.0	104701 (SS) Adj “Normal” Bone-Backus	35.1
111006 Atopic Asthma-F	13.0	104702 (SS) OA Synovium-Backus	63.7
111417 Allergy-M	31.6	117093 OA Cartilage Rep7	30.6
112347 Allergy-M	21.2	112672 OA Bone5	60.3
112349 Normal Lung-F	23.2	112673 OA Synovium5	36.1
112357 Normal Lung-F	70.7	112674 OA Synovial Fluid cells5	24.5
112354 Normal Lung-M	21.9	117100 OA Cartilage Rep14	30.1
112374 Crohns-F	75.3	112756 OA Bone9	35.8
112389 Match Control Crohns-F	32.5	112757 OA Synovium9	8.2
112375 Crohns-F	93.3	112758 OA Synovial Fluid Cells9	32.5
112732 Match Control Crohns-F	7.1	117125 RA Cartilage Rep2	35.1
112725 Crohns-M	23.8	113492 Bone2 RA	19.9
112387 Match Control Crohns-M	40.9	113493 Synovium2 RA	9.0
112378 Crohns-M	21.3	113494 Syn Fluid Cells RA	11.6
112390 Match Control Crohns-M	76.3	113499 Cartilage4 RA	13.3
112726 Crohns-M	61.6	113500 Bone4 RA	12.9
112731 Match Control Crohns-M	30.1	113501 Synovium4 RA	11.9
112380 Ulcer Col-F	39.8	113502 Syn Fluid Cells4 RA	7.6
112734 Match Control Ulcer Col-F	15.0	113495 Cartilage3 RA	15.6
112384 Ulcer Col-F	96.6	113496 Bone3 RA	13.4
112737 Match Control Ulcer Col-F	31.0	113497 Synovium3 RA	8.9
112386 Ulcer Col-F	30.4	113498 Syn Fluid Cells3 RA	16.3
112738 Match Control Ulcer Col-F	11.8	117106 Normal Cartilage Rep20	23.7
112381 Ulcer Col-M	21.0	113663 Bone3 Normal	16.3
112735 Match Control Ulcer Col-M	47.3	113664 Synovium3 Normal	5.2
112382 Ulcer Col-M	24.5	113665 Syn Fluid Cells3 Normal	6.8
112394 Match Control Ulcer Col-M	14.1	117107 Normal Cartilage Rep22	11.2
112383 Ulcer Col-M	85.9	113667 Bone4 Normal	18.2
112736 Match Control Ulcer Col-M	29.9	113668 Synovium4 Normal	25.0
112423 Psoriasis-F	31.6	113669 Syn Fluid Cells4 Normal	27.0

[0730]

TABLE IF
CNS_neurodegeneration_v1.0
	Tissue Name	A	B	C
	AD 1 Hippo	22.1	23.8	29.7
	AD 2 Hippo	47.6	41.5	53.2
	AD 3 Hippo	12.6	11.4	21.6
	AD 4 Hippo	15.1	13.8	17.8
	AD 5 Hippo	99.3	100.0	88.9
	AD 6 Hippo	96.6	76.8	100.0
	Control 2 Hippo	32.1	27.5	28.7
	Control 4 Hippo	48.3	52.1	54.7
	Control (Path) 3 Hippo	19.5	14.7	22.4
	AD 1 Temporal Ctx	22.5	24.7	29.9
	AD 2 Temporal Ctx	47.3	39.2	40.6
	AD 3 Temporal Ctx	19.6	15.5	20.7
	AD 4 Temporal Ctx	35.1	33.0	33.0
	AD 5 Inf Temporal Ctx	96.6	78.5	64.6
	AD 5 Sup Temporal Ctx	65.1	69.3	78.5
	AD 6 Inf Temporal Ctx	68.8	31.6	66.0
	AD 6 Sup Temporal Ctx	82.9	65.5	77.9
	Control 1 Temporal Ctx	10.2	5.4	9.8
	Control 2 Temporal Ctx	32.8	25.0	29.3
	Control 3 Temporal Ctx	20.9	21.8	29.9
	Control 3 Temporal Ctx	15.4	16.0	24.0
	Control (Path) 1 Temporal Ctx	67.8	51.1	73.7
	Control (Path) 2 Temporal Ctx	61.6	42.0	40.6
	Control (Path) 3 Temporal Ctx	9.1	10.2	16.7
	Control (Path) 4 Temporal Ctx	55.1	42.0	33.2
	AD 1 Occipital Ctx	20.6	23.0	24.0
	AD 2 Occipital Ctx (Missing)	0.0	0.0	0.0
	AD 3 Occipital Ctx	10.2	9.8	16.7
	AD 4 Occipital Ctx	27.2	21.0	27.4
	AD 5 Occipital Ctx	22.2	30.6	22.7
	AD 6 Occipital Ctx	30.6	27.9	37.4
	Control 1 Occipital Ctx	6.0	5.3	5.0
	Control 2 Occipital Ctx	44.1	42.3	42.6
	Control 3 Occipital Ctx	29.9	25.9	35.8
	Control 4 Occipital Ctx	12.2	13.5	21.6
	Control (Path) 1 Occipital Ctx	100.0	79.6	76.8
	Control (Path) 2 Occipital Ctx	30.8	18.7	26.2
	Control (Path) 3 Occipital Ctx	7.5	5.1	9.7
	Control (Path) 4 Occipital Ctx	38.2	32.1	39.0
	Control 1 Parietal Ctx	11.9	7.0	15.6
	Control 2 Parietal Ctx	63.3	53.6	57.8
	Control 3 Parietal Ctx	24.0	35.1	21.8
	Control (Path) 1 Parietal Ctx	59.5	53.6	74.2
	Control (Path) 2 Parietal Ctx	55.1	28.1	26.8
	Control (Path) 3 Parietal Ctx	7.6	6.7	7.9
	Control (Path) 4 Parietal Ctx	60.7	50.7	44.8
	Column A - Rel. Exp. (%) Ag1849, Run 207926293
	Column B - Rel. Exp. (%) Ag1849, Run 269216133
	Column C - Rel. Exp. (%) Ag887, Run 225000479

[0731]

TABLE IG
General_screening_panel_v1.5
Column A - Rel. Exp. (%) Ag887, Run 228714727
Tissue Name	A	Tissue Name	A
Adipose	2.5	Renal ca. TK-10	38.4
Melanoma* Hs688(A).T	16.8	Bladder	11.1
Melanoma* Hs688(B).T	21.5	Gastric ca. (liver met.) NCI-N87	37.1
Melanoma* M14	100.0	Gastric ca. KATO III	0.1
Melanoma* LOXIMVI	5.7	Colon ca. SW-948	12.0
Melanoma* SK-MEL-5	22.1	Colon ca. SW480	22.7
Squamous cell carcinoma	12.2	Colon ca.* (SW480 met) SW620	17.0
SCC-4
Testis Pool	2.9	Colon ca. HT29	13.5
Prostate ca.* (bone met)	5.8	Colon ca. HCT-116	26.1
PC-3
Prostate Pool	4.7	Colon ca. CaCo-2	12.7
Placenta	10.2	Colon cancer tissue	25.0
Uterus Pool	2.3	Colon ca. SW1116	7.9
Ovarian ca. OVCAR-3	34.9	Colon ca. Colo-205	1.9
Ovarian ca. SK-OV-3	50.7	Colon ca. SW-48	6.3
Ovarian ca. OVCAR-4	12.1	Colon Pool	5.5
Ovarian ca. OVCAR-5	43.8	Small Intestine Pool	2.6
Ovarian ca. IGROV-1	48.6	Stomach Pool	3.0
Ovarian ca. OVCAR-8	25.0	Bone Marrow Pool	3.4
Ovary	6.6	Fetal Heart	3.6
Breast ca. MCF-7	42.6	Heart Pool	2.3
Breast ca. MDA-	24.5	Lymph Node Pool	6.3
MB-231
Breast ca. BT 549	14.2	Fetal Skeletal Muscle	4.3
Breast ca. T47D	3.2	Skeletal Muscle Pool	3.1
Breast ca. MDA-N	22.8	Spleen Pool	2.7
Breast Pool	5.1	Thymus Pool	4.5
Trachea	4.6	CNS cancer (glio/astro)	39.5
		U87-MG
Lung	1.2	CNS cancer (glio/astro)	37.9
		U-118-MG
Fetal Lung	9.7	CNS cancer (neuro; met)	26.6
		SK-N-AS
Lung ca. NCI-N417	5.2	CNS cancer (astro) SF-539	32.1
Lung ca. LX-1	26.2	CNS cancer (astro) SNB-75	95.9
Lung ca. NCI-H146	8.2	CNS cancer (glio) SNB-19	40.9
Lung ca. SHP-77	12.0	CNS cancer (glio) SF-295	26.6
Lung ca. A549	12.9	Brain (Amygdala) Pool	1.0
Lung ca. NCI-H526	8.8	Brain (cerebellum)	2.0
Lung ca. NCI-H23	25.0	Brain (fetal)	10.3
Lung ca. NCI-H460	11.8	Brain (Hippocampus) Pool	1.3
Lung ca. HOP-62	10.0	Cerebral Cortex Pool	1.3
Lung ca. NCI-H522	23.8	Brain (Substantia nigra) Pool	2.0
Liver	1.8	Brain (Thalamus) Pool	1.6
Fetal Liver	4.6	Brain (whole)	2.4
Liver ca. HepG2	9.3	Spinal Cord Pool	1.5
Kidney Pool	6.6	Adrenal Gland	11.2
Fetal Kidney	7.5	Pituitary gland Pool	0.6
Renal ca. 786-0	23.7	Salivary Gland	3.1
Renal ca. A498	12.2	Thyroid (female)	3.0
Renal ca. ACHN	10.5	Pancreatic ca. CAPAN2	36.6
Renal ca. UO-31	22.4	Pancreas Pool	9.5

[0732]

TABLE IH
General_screening_panel_v1.6
Column A - Rel. Exp. (%) Ag6967, Run 278388952
Tissue Name	A	Tissue Name	A
Adipose	1.9	Renal ca. TK-10	31.2
Melanoma* Hs688(A).T	16.0	Bladder	14.6
Melanoma* Hs688(B).T	24.0	Gastric ca. (liver met.) NCI-N87	43.5
Melanoma* M14	100.0	Gastric ca. KATO III	0.0
Melanoma* LOXIMVI	4.3	Colon ca. SW-948	12.1
Melanoma* SK-MEL-5	21.6	Colon ca. SW480	17.3
Squamous cell carcinoma	12.5	Colon ca.* (SW480 met) SW620	16.0
SCC-4
Testis Pool	3.0	Colon ca. HT29	13.7
Prostate ca.* (bone met)	5.4	Colon ca. HCT-116	30.1
PC-3
Prostate Pool	5.4	Colon ca. CaCo-2	16.3
Placenta	9.2	Colon cancer tissue	31.0
Uterus Pool	1.7	Colon ca. SW1116	7.9
Ovarian ca. OVCAR-3	30.4	Colon ca. Colo-205	2.5
Ovarian ca. SK-OV-3	50.7	Colon ca. SW-48	5.9
Ovarian ca. OVCAR-4	12.9	Colon Pool	7.2
Ovarian ca. OVCAR-5	41.5	Small Intestine Pool	3.7
Ovarian ca. IGROV-1	32.5	Stomach Pool	3.8
Ovarian ca. OVCAR-8	14.6	Bone Marrow Pool	3.9
Ovary	6.2	Fetal Heart	4.5
Breast ca. MCF-7	29.7	Heart Pool	2.9
Breast ca. MDA-MB-231	29.1	Lymph Node Pool	7.9
Breast ca. BT 549	15.3	Fetal Skeletal Muscle	4.7
Breast ca. T47D	3.6	Skeletal Muscle Pool	0.5
Breast ca. MDA-N	18.7	Spleen Pool	3.3
Breast Pool	6.9	Thymus Pool	5.9
Trachea	3.9	CNS cancer (glio/astro)	46.7
		U87-MG
Lung	1.1	CNS cancer (glio/astro)	51.4
		U-118-MG
Fetal Lung	9.2	CNS cancer (neuro; met)	27.5
		SK-N-AS
Lung ca. NCI-N417	6.5	CNS cancer (astro) SF-539	28.9
Lung ca. LX-1	22.1	CNS cancer (astro) SNB-75	74.7
Lung ca. NCI-H146	9.7	CNS cancer (glio) SNB-19	32.5
Lung ca. SHP-77	11.1	CNS cancer (glio) SF-295	30.8
Lung ca. A549	13.5	Brain (Amygdala) Pool	1.4
Lung ca. NCI-H526	7.8	Brain (cerebellum)	2.9
Lung ca. NCI-H23	19.3	Brain (fetal)	9.2
Lung ca. NCI-H460	9.6	Brain (Hippocampus) Pool	1.6
Lung ca. HOP-62	8.0	Cerebral Cortex Pool	1.4
Lung ca. NCI-H522	21.6	Brain (Substantia nigra) Pool	1.4
Liver	1.9	Brain (Thalamus) Pool	1.9
Fetal Liver	5.9	Brain (whole)	1.9
Liver ca. HepG2	4.5	Spinal Cord Pool	1.4
Kidney Pool	7.6	Adrenal Gland	9.3
Fetal Kidney	10.7	Pituitary gland Pool	0.7
Renal ca. 786-0	24.8	Salivary Gland	2.0
Renal ca. A498	15.9	Thyroid (female)	2.8
Renal ca. ACHN	12.0	Pancreatic ca. CAPAN2	32.3
Renal ca. UO-31	25.3	Pancreas Pool	2.4

[0733]

TABLE II
Panel 1.1
	Tissue Name	A	B
	Adrenal gland	17.7	18.9
	Bladder	25.9	33.0
	Brain (amygdala)	1.5	2.1
	Brain (cerebellum)	5.5	7.0
	Brain (hippocampus)	5.4	5.4
	Brain (substantia nigra)	10.4	9.2
	Brain (thalamus)	3.3	4.5
	Cerebral Cortex	6.0	6.5
	Brain (fetal)	10.6	13.8
	Brain (whole)	5.3	6.6
	glio/astro U-118-MG	13.1	14.2
	astrocytoma SF-539	12.8	16.2
	astrocytoma SNB-75	6.6	6.2
	astrocytoma SW1783	7.1	8.2
	glioma U251	28.1	22.2
	glioma SF-295	26.1	22.4
	glioma SNB-19	28.9	27.7
	glio/astro U87-MG	33.9	31.0
	neuro*; met SK-N-AS	51.8	45.7
	Mammary gland	18.8	20.3
	Breast ca. BT-549	7.4	8.0
	Breast ca. MDA-N	21.2	28.9
	Breast ca.* (pl. ef) T47D	14.5	13.6
	Breast ca.* (pl. ef) MCF-7	16.6	16.4
	Breast ca.* (pl. ef) MDA-MB-231	6.1	7.6
	Small intestine	6.0	6.5
	Colorectal	1.5	1.8
	Colon ca. HT29	9.7	9.8
	Colon ca. CaCo-2	12.7	15.3
	Colon ca. HCT-15	12.6	15.5
	Colon ca. HCT-116	12.2	10.7
	Colon ca. HCC-2998	17.1	19.6
	Colon ca. SW480	5.5	5.4
	Colon ca.* SW620 (SW480 met)	11.7	13.9
	Stomach	7.2	8.0
	Gastric ca. (liver met) NCI-N87	40.3	38.4
	Heart	17.4	20.9
	Skeletal muscle (Fetal)	12.6	12.1
	Skeletal muscle	7.8	8.0
	Endothelial cells	49.7	49.0
	Heart (Fetal)	21.6	25.9
	Kidney	10.8	11.3
	Kidney (fetal)	13.6	14.4
	Renal ca. 786-0	11.0	9.0
	Renal ca. A498	50.3	40.9
	Renal ca. ACHN	13.6	12.9
	Renal ca. TK-10	32.5	27.4
	Renal ca. UO-31	11.7	11.7
	Renal ca. RXF 393	8.5	9.3
	Liver	6.8	7.7
	Liver (fetal)	4.8	6.3
	Liver ca. (hepatoblast) HepG2	6.7	7.3
	Lung	3.4	4.0
	Lung (fetal)	10.4	10.7
	Lung ca. (non-s. cell) HOP-62	48.0	62.0
	Lung ca. (large cell)NCI-H460	13.5	13.6
	Lung ca. (non-s. cell) NCI-H23	9.9	9.7
	Lung ca. (non-s. cl) NCI-H522	37.9	40.9
	Lung ca. (non-sm. cell) A549	10.1	11.0
	Lung ca. (s. cell var.) SHP-77	3.2	2.9
	Lung ca. (small cell) LX-1	26.4	25.7
	Lung ca. (small cell) NCI-H69	2.3	2.4
	Lung ca. (squam.) SW 900	14.4	16.6
	Lung ca. (squam.) NCI-H596	0.6	0.6
	Lymph node	2.0	2.5
	Spleen	2.8	3.0
	Thymus	0.7	0.6
	Ovary	20.9	22.7
	Ovarian ca. IGROV-1	21.0	20.7
	Ovarian ca. OVCAR-3	25.9	27.0
	Ovarian ca. OVCAR-4	11.0	13.9
	Ovarian ca. OVCAR-5	43.2	47.3
	Ovarian ca. OVCAR-8	6.9	5.8
	Ovarian ca.* (ascites) SK-OV-3	26.6	33.7
	Pancreas	31.2	29.5
	Pancreatic ca. CAPAN 2	9.2	8.2
	Pituitary gland	7.9	9.3
	Placenta	17.9	18.2
	Prostate	12.4	12.2
	Prostate ca.* (bone met) PC-3	8.8	7.6
	Salivary gland	14.2	17.3
	Trachea	4.5	4.3
	Spinal cord	4.6	4.5
	Testis	3.8	4.1
	Thyroid	7.7	7.8
	Uterus	6.0	7.7
	Melanoma M14	50.3	67.4
	Melanoma LOX IMVI	4.0	4.5
	Melanoma UACC-62	19.2	21.8
	Melanoma SK-MEL-28	100.0	100.0
	Melanoma* (met) SK-MEL-5	19.2	17.2
	Melanoma Hs688(A).T	9.0	10.6
	Melanoma* (met) Hs688(B).T	11.3	14.5
	Column A - Rel. Exp. (%) Ag685, Run 109557296
	Column B - Rel. Exp. (%) Ag685, Run 109557787

[0734]

TABLE IJ
Panel 1.2
Column A - Rel. Exp. (%) Ag887, Run 118840787
Tissue Name	A	Tissue Name	A
Endothelial cells	72.7	Renal ca. 786-0	6.6
Heart (Fetal)	33.2	Renal ca. A498	57.8
Pancreas	48.3	Renal ca. RXF 393	11.6
Pancreatic ca. CAPAN 2	20.2	Renal ca. ACHN	11.0
Adrenal Gland	100.0	Renal ca. UO-31	6.6
Thyroid	18.7	Renal ca. TK-10	18.9
Salivary gland	34.6	Liver	33.4
Pituitary gland	32.3	Liver (fetal)	25.2
Brain (fetal)	70.2	Liver ca. (hepatoblast) HepG2	6.3
Brain (whole)	26.1	Lung	19.9
Brain (amygdala)	16.6	Lung (fetal)	34.6
Brain (cerebellum)	21.3	Lung ca. (small cell) LX-1	32.8
Brain (hippocampus)	22.8	Lung ca. (small cell) NCI-H69	3.5
Brain (thalamus)	12.1	Lung ca. (s. cell var.) SHP-77	4.9
Cerebral Cortex	16.4	Lung ca. (large cell)NCI-H460	24.7
Spinal cord	11.5	Lung ca. (non-sm. cell) A549	11.3
glio/astro U87-MG	33.7	Lung ca. (non-s. cell) NCI-H23	9.9
glio/astro U-118-MG	20.2	Lung ca. (non-s. cell) HOP-62	37.1
astrocytoma SW1783	10.3	Lung ca. (non-s. cl) NCI-H522	54.0
neuro*; met SK-N-AS	47.0	Lung ca. (squam.) SW 900	12.2
astrocytoma SF-539	17.7	Lung ca. (squam.) NCI-H596	1.6
astrocytoma SNB-75	9.2	Mammary gland	85.3
glioma SNB-19	39.0	Breast ca.* (pl. ef) MCF-7	35.6
glioma U251	30.1	Breast ca.* (pl. ef)	9.1
		MDA-MB-231
glioma SF-295	22.2	Breast ca.* (pl. ef) T47D	20.2
Heart	46.0	Breast ca. BT-549	15.8
Skeletal Muscle	24.8	Breast ca. MDA-N	33.0
Bone marrow	2.4	Ovary	29.5
Thymus	2.0	Ovarian ca. OVCAR-3	42.0
Spleen	10.2	Ovarian ca. OVCAR-4	22.1
Lymph node	9.0	Ovarian ca. OVCAR-5	38.2
Colorectal Tissue	2.7	Ovarian ca. OVCAR-8	6.4
Stomach	20.6	Ovarian ca. IGROV-1	23.7
Small intestine	26.1	Ovarian ca. (ascites) SK-OV-3	44.8
Colon ca. SW480	3.6	Uterus	19.2
Colon ca.* SW620	9.2	Placenta	57.4
(SW480 met)
Colon ca. HT29	7.9	Prostate	48.0
Colon ca. HCT-116	11.0	Prostate ca.* (bone met) PC-3	11.2
Colon ca. CaCo-2	14.4	Testis	24.5
Colon ca. Tissue	3.5	Melanoma Hs688(A). T	19.6
(ODO3866)
Colon ca. HCC-2998	20.9	Melanoma* (met) Hs688(B). T	21.5
Gastric ca.* (liver met)	45.1	Melanoma UACC-62	46.7
NCI-N87
Bladder	77.4	Melanoma M14	67.4
Trachea	10.2	Melanoma LOX IMVI	8.5
Kidney	11.7	Melanoma* (met) SK-MEL-5	31.4
Kidney (fetal)	75.3

[0735]

TABLE IK
Panel 1.3D
Column A - Rel. Exp. (%) Ag1849, Run 150082466
Tissue Name	A	Tissue Name	A
Liver adenocarcinoma	42.6	Kidney (fetal)	19.6
Pancreas	7.1	Renal ca. 786-0	17.0
Pancreatic ca. CAPAN 2	16.0	Renal ca. A498	88.3
Adrenal gland	17.7	Renal ca. RXF 393	18.4
Thyroid	9.7	Renal ca. ACHN	14.6
Salivary gland	7.1	Renal ca. UO-31	32.8
Pituitary gland	8.4	Renal ca. TK-10	17.3
Brain (fetal)	15.9	Liver	5.2
Brain (whole)	8.2	Liver (fetal)	16.3
Brain (amygdala)	14.6	Liver ca. (hepatoblast) HepG2	14.3
Brain (cerebellum)	0.9	Lung	9.9
Brain (hippocampus)	41.8	Lung (fetal)	20.6
Brain (substantia nigra)	3.3	Lung ca. (small cell) LX-1	16.4
Brain (thalamus)	7.1	Lung ca. (small cell) NCI-H69	4.3
Cerebral Cortex	13.9	Lung ca. (s. cell var.) SHP-77	10.2
Spinal cord	5.6	Lung ca. (large cell)NCI-H460	8.2
glio/astro U87-MG	36.3	Lung ca. (non-sm. cell) A549	5.8
glio/astro U-118-MG	67.8	Lung ca. (non-s. cell) NCI-H23	27.4
astrocytoma SW1783	28.1	Lung ca. (non-s. cell) HOP-62	25.2
neuro*; met SK-N-AS	48.6	Lung ca. (non-s. cl) NCI-H522	22.5
astrocytoma SF-539	34.4	Lung ca. (squam.) SW 900	23.8
astrocytoma SNB-75	40.6	Lung ca. (squam.) NCI-H596	0.3
glioma SNB-19	42.6	Mammary gland	38.7
glioma U251	39.2	Breast ca.* (pl. ef) MCF-7	19.8
glioma SF-295	41.2	Breast ca.* (pl. ef)	24.3
		MDA-MB-231
Heart (fetal)	39.8	Breast ca.* (pl. ef) T47D	21.0
Heart	4.3	Breast ca. BT-549	20.7
Skeletal muscle (fetal)	100.0	Breast ca. MDA-N	20.9
Skeletal muscle	1.3	Ovary	76.3
Bone marrow	1.3	Ovarian ca. OVCAR-3	15.4
Thymus	1.6	Ovarian ca. OVCAR-4	6.1
Spleen	19.1	Ovarian ca. OVCAR-5	31.4
Lymph node	5.8	Ovarian ca. OVCAR-8	8.8
Colorectal	21.9	Ovarian ca. IGROV-1	8.9
Stomach	12.6	Ovarian ca.* (ascites) SK-OV-3	23.2
Small intestine	25.9	Uterus	23.3
Colon ca. SW480	24.0	Placenta	25.3
Colon ca.* SW620	7.9	Prostate	27.5
(SW480 met)
Colon ca. HT29	15.0	Prostate ca.* (bone met)PC-3	4.6
Colon ca. HCT-116	13.2	Testis	13.6
Colon ca. CaCo-2	28.5	Melanoma Hs688(A). T	58.6
Colon ca. tissue	31.2	Melanoma* (met) Hs688(B). T	75.8
(ODO3866)
Colon ca. HCC-2998	19.3	Melanoma UACC-62	10.0
Gastric ca.* (liver met)	40.1	Melanoma M14	58.6
NCI-N87
Bladder	10.2	Melanoma LOX IMVI	6.5
Trachea	16.2	Melanoma* (met) SK-MEL-5	16.5
Kidney	3.2	Adipose	12.5

[0736]

TABLE IL
Panel 2D
Column A - Rel. Exp. (%) Ag1849, Run 150082509
Tissue Name	A	Tissue Name	A
Normal Colon	40.6	Kidney Margin 8120608	15.8
CC Well to Mod Diff (ODO3866)	36.9	Kidney Cancer 8120613	17.3
CC Margin (ODO3866)	9.6	Kidney Margin 8120614	12.2
CC Gr.2 rectosigmoid (ODO3868)	21.9	Kidney Cancer 9010320	54.0
CC Margin (ODO3868)	5.1	Kidney Margin 9010321	24.1
CC Mod Diff (ODO3920)	40.9	Normal Uterus	15.9
CC Margin (ODO3920)	13.7	Uterus Cancer 064011	21.5
CC Gr.2 ascend colon (ODO3921)	47.3	Normal Thyroid	16.4
CC Margin (ODO3921)	18.0	Thyroid Cancer 064010	35.1
CC from Partial Hepatectomy (ODO4309)	46.0	Thyroid Cancer A302152	21.3
Mets
Liver Margin (ODO4309)	37.6	Thyroid Margin A302153	15.1
Colon mets to lung (OD04451-01)	23.3	Normal Breast	27.4
Lung Margin (OD04451-02)	16.0	Breast Cancer (OD04566)	41.8
Normal Prostate 6546-1	43.2	Breast Cancer (OD04590-01)	52.1
Prostate Cancer (OD04410)	66.0	Breast Cancer Mets (OD04590-03)	63.3
Prostate Margin (OD04410)	53.2	Breast Cancer Metastasis	51.1
		(OD04655-05)
Prostate Cancer (OD04720-01)	50.7	Breast Cancer 064006	49.7
Prostate Margin (OD04720-02)	65.5	Breast Cancer 1024	59.0
Normal Lung 061010	26.2	Breast Cancer 9100266	69.7
Lung Met to Muscle (ODO4286)	41.2	Breast Margin 9100265	34.4
Muscle Margin (ODO4286)	17.1	Breast Cancer A209073	63.7
Lung Malignant Cancer (OD03126)	70.2	Breast Margin A209073	31.4
Lung Margin (OD03126)	32.3	Normal Liver	16.2
Lung Cancer (OD04404)	77.4	Liver Cancer 064003	15.4
Lung Margin (OD04404)	23.5	Liver Cancer 1025	17.1
Lung Cancer (OD04565)	49.3	Liver Cancer 1026	31.4
Lung Margin (OD04565)	19.2	Liver Cancer 6004-T	21.9
Lung Cancer (OD04237-01)	44.4	Liver Tissue 6004-N	29.3
Lung Margin (OD04237-02)	31.2	Liver Cancer 6005-T	27.5
Ocular Mel Met to Liver (ODO4310)	29.7	Liver Tissue 6005-N	14.2
Liver Margin (ODO4310)	17.4	Normal Bladder	59.0
Melanoma Mets to Lung (OD04321)	37.9	Bladder Cancer 1023	22.1
Lung Margin (OD04321)	31.6	Bladder Cancer A302173	89.5
Normal Kidney	18.8	Bladder Cancer (OD04718-01)	65.1
Kidney Ca, Nuclear grade 2 (OD04338)	54.0	Bladder Normal Adjacent	44.8
		(OD04718-03)
Kidney Margin (OD04338)	12.9	Normal Ovary	39.8
Kidney Ca Nuclear grade 1/2 (OD04339)	28.7	Ovarian Cancer 064008	74.7
Kidney Margin (OD04339)	16.7	Ovarian Cancer (OD04768-07)	45.1
Kidney Ca, Clear cell type (OD04340)	66.0	Ovary Margin (OD04768-08)	26.1
Kidney Margin (OD04340)	19.5	Normal Stomach	14.9
Kidney Ca, Nuclear grade 3 (OD04348)	100.0	Gastric Cancer 9060358	9.4
Kidney Margin (OD04348)	18.9	Stomach Margin 9060359	15.2
Kidney Cancer (OD04622-01)	79.0	Gastric Cancer 9060395	20.7
Kidney Margin (OD04622-03)	5.6	Stomach Margin 9060394	23.5
Kidney Cancer (OD04450-01)	44.4	Gastric Cancer 9060397	53.6
Kidney Margin (OD04450-03)	10.5	Stomach Margin 9060396	9.8
Kidney Cancer 8120607	31.6	Gastric Cancer 064005	31.2

[0737]

TABLE IM
Panel 4.1D
Column A - Rel. Exp. (%) Ag887, Run 175179597
Tissue Name	A	Tissue Name	A
Secondary Th1 act	9.2	HUVEC IL-1beta	19.2
Secondary Th2 act	6.9	HUVEC IFN gamma	16.7
Secondary Tr1 act	6.2	HUVEC TNF alpha + IFN gamma	10.3
Secondary Th1 rest	0.6	HUVEC TNF alpha + IL4	20.0
Secondary Th2 rest	0.5	HUVEC IL-11	12.9
Secondary Tr1 rest	0.6	Lung Microvascular EC none	23.2
Primary Th1 act	1.2	Lung Microvascular EC TNF alpha + IL-	20.4
		1beta
Primary Th2 act	1.8	Microvascular Dermal EC none	9.1
Primary Tr1 act	1.0	Microsvasular Dermal EC TNF alpha + IL-	8.0
		1beta
Primary Th1 rest	0.0	Bronchial epithelium TNF alpha + IL1beta	12.9
Primary Th2 rest	0.1	Small airway epithelium none	7.2
Primary Tr1 rest	0.0	Small airway epithelium TNF alpha + IL-	17.0
		1beta
CD45RA CD4 lymphocyte act	11.3	Coronery artery SMC rest	22.4
CD45RO CD4 lymphocyte act	0.5	Coronery artery SMC TNF alpha + IL-1beta	29.9
CD8 lymphocyte act	0.4	Astrocytes rest	19.3
Secondary CD8 lymphocyte rest	0.7	Astrocytes TNF alpha + IL-1beta	20.7
Secondary CD8 lymphocyte act	0.6	KU-812 (Basophil) rest	1.3
CD4 lymphocyte none	0.0	KU-812 (Basophil) PMA/ionomycin	3.6
2ry Th1/Th2/Tr1_anti-CD95	0.0	CCD1106 (Keratinocytes) none	31.2
CH11
LAK cells rest	16.6	CCD1106 (Keratinocytes) TNF alpha + IL-	21.5
		1beta
LAK cells IL-2	0.6	Liver cirrhosis	2.5
LAK cells IL-2 + IL-12	1.1	NCI-H292 none	16.2
LAK cells IL-2 + IFN gamma	1.1	NCI-H292 IL-4	22.7
LAK cells IL-2 + IL-18	0.8	NCI-H292 IL-9	18.8
LAK cells PMA/ionomycin	17.4	NCI-H292 IL-13	23.3
NK Cells IL-2 rest	0.7	NCI-H292 IFN gamma	18.7
Two Way MLR 3 day	6.1	HPAEC none	9.7
Two Way MLR 5 day	8.7	HPAEC TNF alpha + IL-1beta	26.2
Two Way MLR 7 day	2.3	Lung fibroblast none	22.8
PBMC rest	0.1	Lung fibroblast TNF alpha + IL-1beta	19.8
PBMC PWM	2.1	Lung fibroblast IL-4	34.6
PBMC PHA-L	1.2	Lung fibroblast IL-9	16.4
Ramos (B cell) none	0.0	Lung fibroblast IL-13	24.8
Ramos (B cell) ionomycin	0.0	Lung fibroblast IFN gamma	34.6
B lymphocytes PWM	1.1	Dermal fibroblast CCD1070 rest	32.3
B lymphocytes CD40L and IL-4	0.5	Dermal fibroblast CCD1070 TNF alpha	28.7
EOL-1 dbcAMP	3.4	Dermal fibroblast CCD1070 IL-1beta	21.6
EOL-1 dbcAMP PMA/ionomycin	67.8	Dermal fibroblast IFN gamma	39.5
Dendritic cells none	55.1	Dermal fibroblast IL-4	39.0
Dendritic cells LPS	55.5	Dermal Fibroblasts rest	38.4
Dendritic cells anti-CD40	100.0	Neutrophils TNFa + LPS	2.9
Monocytes rest	0.0	Neutrophils rest	4.7
Monocytes LPS	20.6	Colon	4.0
Macrophages rest	69.7	Lung	14.5
Macrophages LPS	36.3	Thymus	2.3
HUVEC none	14.3	Kidney	8.1
HUVEC starved	14.8

[0738]

TABLE IN
Panel 4D
Column A - Rel. Exp. (%) Ag1849, Run 150082695
Tissue Name	A	Tissue Name	A
Secondary Th1 act	8.2	HUVEC IL-1beta	13.7
Secondary Th2 act	4.4	HUVEC IFN gamma	19.3
Secondary Tr1 act	8.3	HUVEC TNF alpha + IFN gamma	14.5
Secondary Th1 rest	0.0	HUVEC TNF alpha + IL4	19.6
Secondary Th2 rest	0.4	HUVEC IL-11	21.3
Secondary Tr1 rest	0.1	Lung Microvascular EC none	17.4
Primary Th1 act	1.2	Lung Microvascular EC TNF alpha + IL-	24.5
		1beta
Primary Th2 act	0.9	Microvascular Dermal EC none	16.7
Primary Tr1 act	1.5	Microsvasular Dermal EC TNF alpha + IL-	14.9
		1beta
Primary Th1 rest	0.1	Bronchial epithelium TNF alpha + IL1beta	29.5
Primary Th2 rest	0.3	Small airway epithelium none	15.5
Primary Tr1 rest	0.0	Small airway epithelium TNF alpha + IL-	46.7
		1beta
CD45RA CD4 lymphocyte act	8.5	Coronery artery SMC rest	40.1
CD45RO CD4 lymphocyte act	5.1	Coronery artery SMC TNF alpha + IL-1beta	26.4
CD8 lymphocyte act	0.1	Astrocytes rest	33.9
Secondary CD8 lymphocyte rest	0.5	Astrocytes TNF alpha + IL-1beta	34.2
Secondary CD8 lymphocyte act	0.8	KU-812 (Basophil) rest	0.0
CD4 lymphocyte none	0.0	KU-812 (Basophil) PMA/ionomycin	6.7
2ry Th1/Th2/Tr1_anti-CD95	0.2	CCD1106 (Keratinocytes) none	28.3
CH11
LAK cells rest	22.7	CCD1106 (Keratinocytes) TNF alpha + IL-	24.8
		1beta
LAK cells IL-2	0.1	Liver cirrhosis	4.0
LAK cells IL-2 + IL-12	1.9	Lupus kidney	2.3
LAK cells IL-2 + IFN gamma	3.7	NCI-H292 none	26.4
LAK cells IL-2 + IL-18	2.9	NCI-H292 IL-4	36.9
LAK cells PMA/ionomycin	19.5	NCI-H292 IL-9	29.3
NK Cells IL-2 rest	0.3	NCI-H292 IL-13	20.3
Two Way MLR 3 day	9.8	NCI-H292 IFN gamma	23.2
Two Way MLR 5 day	8.5	HPAEC none	21.8
Two Way MLR 7 day	1.9	HPAEC TNF alpha + IL-1beta	30.8
PBMC rest	0.0	Lung fibroblast none	24.8
PBMC PWM	2.5	Lung fibroblast TNF alpha + IL-1beta	23.3
PBMC PHA-L	1.0	Lung fibroblast IL-4	55.5
Ramos (B cell) none	0.0	Lung fibroblast IL-9	35.8
Ramos (B cell) ionomycin	0.0	Lung fibroblast IL-13	32.3
B lymphocytes PWM	4.7	Lung fibroblast IFN gamma	41.8
B lymphocytes CD40L and IL-4	0.6	Dermal fibroblast CCD1070 rest	49.0
EOL-1 dbcAMP	1.5	Dermal fibroblast CCD1070 TNF alpha	31.0
EOL-1 dbcAMP PMA/ionomycin	70.2	Dermal fibroblast CCD1070 IL-1beta	28.1
Dendritic cells none	75.3	Dermal fibroblast IFN gamma	31.2
Dendritic cells LPS	62.4	Dermal fibroblast IL-4	56.3
Dendritic cells anti-CD40	100.0	IBD Colitis 2	0.8
Monocytes rest	0.0	IBD Crohn's	1.5
Monocytes LPS	9.2	Colon	6.3
Macrophages rest	91.4	Lung	18.6
Macrophages LPS	37.6	Thymus	5.6
HUVEC none	22.5	Kidney	2.8
HUVEC starved	28.9

[0739]

TABLE IO
general oncology screening panel _v_2.4
Column A - Rel. Exp. (%) Ag887, Run 260286541
Tissue Name	A	Tissue Name	A
Colon cancer 1	42.6	Bladder cancer NAT 2	0.7
Colon cancer NAT 1	20.9	Bladder cancer NAT 3	1.5
Colon cancer 2	51.8	Bladder cancer NAT 4	6.4
Colon cancer NAT 2	3.4	Prostate adenocarcinoma 1	20.4
Colon cancer 3	55.9	Prostate adenocarcinoma 2	5.8
Colon cancer NAT 3	12.9	Prostate adenocarcinoma 3	8.0
Colon malignant cancer 4	85.3	Prostate adenocarcinoma 4	20.7
Colon normal adjacent	3.1	Prostate cancer NAT 5	3.4
tissue 4
Lung cancer 1	27.2	Prostate adenocarcinoma 6	6.9
Lung NAT 1	1.7	Prostate adenocarcinoma 7	6.1
Lung cancer 2	73.7	Prostate adenocarcinoma 8	1.5
Lung NAT 2	2.8	Prostate adenocarcinoma 9	19.3
Squamous cell carcinoma 3	59.0	Prostate cancer NAT 10	1.3
Lung NAT 3	0.5	Kidney cancer 1	29.9
metastatic melanoma 1	12.1	KidneyNAT 1	4.4
Melanoma 2	15.6	Kidney cancer 2	100.0
Melanoma 3	5.7	Kidney NAT 2	11.7
metastatic melanoma 4	39.8	Kidney cancer 3	10.7
metastatic melanoma 5	42.0	Kidney NAT 3	1.7
Bladder cancer 1	4.7	Kidney cancer 4	20.3
Bladder cancer NAT 1	0.0	Kidney NAT 4	5.6
Bladder cancer 2	5.4

[0740] AI_comprehensive panel_v1.0 Summary: Ag1849 Highest expression is seen in an OA bone sample (CT=27.2). Gene expression is detected at moderate levels in most tissues in this panel, with lower levels of expression seen in samples derived from RA patients.

[0741] CNS_neurodegeneration_v1.0 Summary: Ag1849/Ag887 Using multivariant analysis this gene is found to be upregulated in the temporal cortex of Alzheimer's disease patients. Therefore, therapeutic modulation of the expression or function of this gene may decrease neuronal death and be of use in the treatment of this disease.

[0742] General_screening_panel_v1.5 Summary: Ag887 Highest expression of this gene is seen in M14 melanoma cell line (CT=26), with moderate to high expression seen in brain, colon, gastric, lung, breast, ovarian, and other melanoma cancer cell lines. This expression profile suggests a role for this gene product in cell survival and proliferation. Modulation of this gene product will be useful in the treatment of cancer.

[0743] Among tissues with metabolic function, this gene is expressed at low but significant levels in pituitary, adipose, adrenal gland, pancreas, thyroid, and adult and fetal skeletal muscle, heart, and liver. This widespread expression shows that this gene product plays 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. Modulation of this gene or gene product is useful in treating these disorders.

[0744] This gene is expressed at low but significant levels in the CNS, including hippocampus, thalamus, substantia nigra, amygdala, cerebellum and cerebral cortex. Therefore, therapeutic modulation of the expression or function of this gene will be useful in the treatment of neurologic disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, multiple sclerosis, stroke and epilepsy.

[0745] General_screening_panel_v1.6 Summary: Ag6967 Highest expression of this gene is seen in a melanoma cell line. Expression patterns seen with this panel are similar to that of Panel 1.5.

[0746] Panel 1.1 Summary: Ag685 Highest expression is seen in a melanoma cell line (CTs=21), in agreement with expression in the other General_Screening_Panels.

[0747] Panel 1.2 Summary: Ag887 Highest expression is seen in the adrenal gland (CT=26). This gene is expressed at higher levels in fetal kidney tissue (CT=26) than in adult (CT=29). The relative overexpression of this gene in fetal kidney suggests that the protein product may enhance kidney growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of kidney related diseases.

[0748] Panel 1.3D Summary: Ag1849 Highest expression is seen in skeletal muscle (CT=26). This gene is expressed at higher levels in fetal skeletal muscle and heart tissue (CTs=26-28) than in adult (CTs=31-33). The relative overexpression of this gene in fetal skeletal muscle and heart suggests that the protein product may enhance heart and muscle growth or development in the fetus and thus may also act in a regenerative capacity in the adult. Therefore, therapeutic modulation of the protein encoded by this gene could be useful in treatment of heart and muscle related diseases.

[0749] Panel 2D Summary: Ag1849 Highest expression is seen in kidney cancer (CT=25.5), with prominent expression in breast cancer samples. This gene is overexpressed in kidney cancer samples compared to normal kidney. Expression of this gene could be used to differentiate between kidney cancer and normal kidney tissue and as a marker of kidney cancer. Furthermore, therapeutic modulation of the expression or function of this gene product will be useful in the treatment of kidney and breast cancer.

[0750] Panel 4.1D Summary: Ag887 This gene is highly expressed in dendritic cells (DC) and is upregulated in response to LPS or CD40 (CT=27.7). Moderate to high levels of expression are seen in EOL eosinophil cell line treated with PMA/ionomycin, activated and resting macrophages, monocytes, dermal and lung fibroblasts, and keratinocytes. Therapeutic use of the protein encoded by this gene is important in immune modulation, organ/bone marrow transplantation, and the treatment of diseases where antigen presentation (a function of mature dendritic cells) plays an important role such as asthma, rheumatoid arthritis, IBD, and psoriasis.

[0751] Panel 4D Summary: Ag1849 Highest expression is seen in CD40 treated dendritic cells (CT=25.5). Gene expression patterns are similar to that seen in Panel 4.1D.

[0752] General oncology screening panel_v—2.4 Summary: Ag887 Highest expression of this gene is seen in a kidney cancer (CT=3 1), and expression is higher in colon and kidney cancer than in normal adjacent tissue. Thus, expression of this gene could be used to detect cancer cells in these tissues and/or as a marker of these cancers. Furthemore, therapeutic modulation of the expression or function of this gene product will be useful in the treatment of colon and kidney cancer.

J. NOV 11, CG94562-01: Novel Agrin-Like Protein with EGF and Laminin G Domains

[0753] Expression of gene CG94562-01 was assessed using the primer-probe set Ag1023, described in Table JA. Results of the RTQ-PCR runs are shown in Tables JB and JC.

TABLE JA
Probe Name Ag1023
			Start	SEQ ID
Primers	Sequences	Length	Position	No
Forward	5′-atggtgtcctcctgtacagcta-3′	22	783	237
Probe	TET-5′-acaggcagcaaagacttcctgtccat-3′-	26	809	238
	TAMRA
Reverse	5′-ccacagtcaaagcggaact-3′	19	858	239

[0754]

TABLE JB
General_screening_panel_v1.5
Column A - Rel. Exp. (%) Ag1023, Run 259427849
Tissue Name	A	Tissue Name	A
Adipose	4.0	Renal ca. TK-10	0.0
Melanoma* Hs688(A).T	0.0	Bladder	2.5
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	0.5	Colon ca. SW480	2.7
Squamous cell carcinoma	0.0	Colon ca.* (SW480 met) SW620	0.0
SCC-4
Testis Pool	29.1	Colon ca. HT29	0.0
Prostate ca.* (bone met)	0.0	Colon ca. HCT-116	0.0
PC-3
Prostate Pool	23.3	Colon ca. CaCo-2	0.0
Placenta	64.6	Colon cancer tissue	13.9
Uterus Pool	17.0	Colon ca. SW1116	0.0
Ovarian ca. OVCAR-3	0.8	Colon ca. Colo-205	0.0
Ovarian ca. SK-OV-3	0.0	Colon ca. SW-48	0.0
Ovarian ca. OVCAR-4	0.0	Colon Pool	17.0
Ovarian ca. OVCAR-5	0.0	Small Intestine Pool	7.3
Ovarian ca. IGROV-1	0.0	Stomach Pool	9.3
Ovarian ca. OVCAR-8	0.0	Bone Marrow Pool	9.5
Ovary	23.3	Fetal Heart	20.9
Breast ca. MCF-7	0.7	Heart Pool	27.5
Breast ca. MDA-MB-231	0.0	Lymph Node Pool	18.6
Breast ca. BT 549	0.0	Fetal Skeletal Muscle	33.2
Breast ca. T47D	0.0	Skeletal Muscle Pool	98.6
Breast ca. MDA-N	0.0	Spleen Pool	2.5
Breast Pool	12.2	Thymus Pool	13.1
Trachea	1.0	CNS cancer (glio/astro)	0.0
		U87-MG
Lung	13.3	CNS cancer (glio/astro)	0.0
		U-118-MG
Fetal Lung	36.9	CNS cancer (neuro; met)	100.0
		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)	6.0
Lung ca. NCI-H23	0.0	Brain (fetal)	4.7
Lung ca. NCI-H460	0.0	Brain (Hippocampus) Pool	2.4
Lung ca. HOP-62	0.0	Cerebral Cortex Pool	1.1
Lung ca. NCI-H522	0.0	Brain (Substantia nigra) Pool	0.6
Liver	1.0	Brain (Thalamus) Pool	1.9
Fetal Liver	57.0	Brain (whole)	0.5
Liver ca. HepG2	0.0	Spinal Cord Pool	3.4
Kidney Pool	18.2	Adrenal Gland	15.6
Fetal Kidney	9.9	Pituitary gland Pool	1.1
Renal ca. 786-0	0.0	Salivary Gland	0.9
Renal ca. A498	0.0	Thyroid (female)	3.3
Renal ca. ACHN	0.0	Pancreatic ca. CAPAN2	0.0
Renal ca. UO-31	0.0	Pancreas Pool	14.1

[0755]

TABLE JC
general oncology screening panel_v_2.4
Tissue Name                    A
Colon cancer 1                 13.0
Colon cancer NAT 1             2.5
Colon cancer 2                 4.1
Colon cancer NAT 2             1.8
Colon cancer 3                 12.2
Colon cancer NAT 3             7.3
Colon malignant cancer 4       10.7
Colon normal adjacent tissue 4 0.5
Lung cancer 1                  4.8
Lung NAT 1                     0.0
Lung cancer 2                  35.8
Lung NAT 2                     0.0
Squamous cell carcinoma 3      7.2
Lung NAT 3                     0.0
metastatic melanoma 1          8.9
Melanoma 2                     3.2
Melanoma 3                     2.3
metastatic melanoma 4          37.1
metastatic melanoma 5          41.2
Bladder cancer 1               0.3
Bladder cancer NAT 1           0.0
Bladder cancer 2               2.1
Bladder cancer NAT 2           0.0
Bladder cancer NAT 3           0.0
Bladder cancer NAT 4           2.9
Prostate adenocarcinoma 1      100.0
Prostate adenocarcinoma 2      7.4
Prostate adenocarcinoma 3      3.2
Prostate adenocarcinoma 4      4.9
Prostate cancer NAT 5          3.7
Prostate adenocarcinoma 6      4.5
Prostate adenocarcinoma 7      9.5
Prostate adenocarcinoma 8      0.7
Prostate adenocarcinoma 9      52.5
Prostate cancer NAT 10         1.0
Kidney cancer 1                12.4
Kidney NAT 1                   1.3
Kidney cancer 2                52.9
Kidney NAT 2                   2.1
Kidney cancer 3                1.6
Kidney NAT 3                   0.5
Kidney cancer 4                9.9
Kidney NAT 4                   0.6
Column A - Rel. Exp. (%) Ag1023, Run 259807101

[0756] General_screening_panel_v1.5 Summary: Ag1023 Highest expression is seen in a brain cancer cell line (CT=3 1.8). Low but significant expression is seen in normal tissues including fetal and adult kidney, skeletal muscle and lung, pancreas, adrenal, fetal liver, lymph node, breast, ovary, placenta and prostate.

[0757] General oncology screening panel_v—2.4 Summary: Ag1023 Highest expression is seen in a prostate cancer sample (CT=32) with expression also seen in kidney, lung and melanoma cancer. Gene expression or detection of its protein product will be used for detection of these cancers. Therapeutic modulation of this gene or its protein product will be useful in the treatment of melanoma, kidney, prostate, and lung cancers.

Example D

Gene Expression Analysis using CuraChip

[0758] CuraGen has developed a gene microarray (CuraChip 1.2) for target identification. It provides a high-throughput means of global mRNA expression analyses of CuraGen's collection of cDNA sequences representing the Pharmaceutically Tractable Genome (PTG). This sequence set includes genes which can be developed into protein therapeutics, or used to develop antibody or small molecule therapeutics. CuraChip 1.2 contains ˜11,000 oligos representing approximately 8,500 gene loci, including (but not restricted to) kinases, ion channels, G-protein coupled receptors (GPCRs), nuclear hormone receptors, proteases, transporters, metabolic enzymes, hormones, growth factors, chemokines, cytokines, complement and coagulation factors, and cell surface receptors.

[0759] The CuraChip cDNAs were represented as 30-mer oligodeoxyribonucleotides (oligos) on a glass microchip. Hybridization methods using the longer CuraChip oligos are more specific compared to methods using 25-mer oligos. CuraChip oligos were synthesized with a linker, purified to remove truncated oligos (which can influence hybridization strength and specificity), and spotted on a glass slide. Oligo-dT primers were used to generate cRNA probes for hybridization from samples of interest. A biotin-avidin conjugation system was used to detect hybridized probes with a fluorophore-labeled secondary antibody. Gene expression was analyzed using clustering and correlation bioinformatics tools such as Spotfire® (Spotfire, Inc., 212 Elm Street, Somerville, Mass. 02144) and statistical tools such as multivariate analysis (MVA).

[0760] Normalization Method Used in CuraChip Software

[0761] The median fluorescence intensity of each spot and a background for each spot is read on a scale from 0 to 65,000. CuraGen's CuraChip software, presents the user with either the raw data (median intensities) or normalized data.

[0762] Results of PTG Chip 1.2, NOV10, CG59932:

[0763] Samples of RNA from tissues obtained from surgically dissected disease- and non-disease tissues, and treated and untreated cell lines, tumors and matched tissues, tumor xenografts grown in nude nu/nu mices were used to generate probes and run on PTG Chip 1.2. An oligo (optg2—0014957) that corresponds to NOV 10, CG59932-01 on the PTG Chip 1.2 was analyzed for its expression profile Table El. The statistical analysis identify strong expression in lung, melanomas and breast cancers.

[0764] Thus, based upon its profile, the expression of this gene could be of use as a marker for subsets of lung, melanomas and breast cancers. In addition, therapeutic inhibition of the activity of the gene or gene product, through the use of for example, antibodies or small molecule drugs, will be useful in the therapy of lung, melanomas and breast cancers that express CG59932-01.

TABLE E1
	Fore-	Back-
	ground	ground	optg2—
Sample	Mean	Mean	0014957
Lung cancer(35C)	2536.51	22.17	8
Lung NAT(36A)	2733.37	20.31	0
Lung cancer(35E)	2933.33	21.31	34
Lung cancer(365)	3808.15	19.58	54
Lung cancer(368)	3824.5	21.07	7
Lung cancer(369)	2825.08	18.76	18
Lung cancer(36E)	4152.87	26.78	9
Lung NAT(36F)	3538.73	23.55	50.5
Lung cancer(370)	4143.89	21.18	17
Lung cancer(376)	2446.38	20.81	5
Lung cancer(378)	3989.95	27.35	4
Lung cancer(37A)	4136.72	36.64	7
Normal Lung 4	4083.27	28.46	35.5
Normal Lung 5	4235.38	25.22	17
CuraChip reference 1	3728.44	28.62	21
Melanoma	2915.57	20.5	19
Melanoma	2646.56	20.29	37
Melanoma (19585)	2509.13	23.23	18
Normal Lung 1	2759.91	24.22	NA
Lung cancer(372)	3803.04	27.08	NA
Lung NAT(35D)	3771.95	25.68	58
Lung NAT(361)	2214.53	20.77	0
Melanoma	2134.94	21.43	12.5
Normal Lung 2	3656.2	20.99	34
Lung cancer(374)	3295.08	24.19	110
Lung cancer(36B)	3776.14	21.32	70.5
Lung cancer(362)	1543.94	26.44	14
Lung cancer(358)	1929.4	30.01	25
Melanoma	2375.7	20.83	17
Normal Lung 3	3157.31	22.69	41
Lung NAT(375)	4614.72	32.86	112
Lung cancer(36D)	2785.76	24.74	13
Lung NAT(363)	4348.91	34.21	45
Lung cancer(35A)	3986.34	29.19	59
Melanoma	2189.36	20.44	8.5
Prostate cancer(B8B)	2957.66	9.6	15
Prostate cancer(B88)	4126.76	33.25	0
Prostate NAT(B93)	3378.81	37.92	47
Prostate cancer(B8C)	3527	42.55	0
Prostate cancer(AD5)	4105.44	45.35	0
Prostate NAT(AD6)	4196.5	41.71	0
Prostate cancer(AD7)	2830.59	42.73	0
Prostate NAT(AD8)	3404.14	29.72	0
Prostate cancer(ADA)	3700.09	34.54	0
Prostate NAT(AD9)	3022.26	30.92	12.5
Prostate cancer(9E7)	3084.26	30.48	0
Prostate cancer(A0A)	3983.11	24.56	7
Prostate cancer(9E2)	2889.43	23.94	2
Pancreatic cancer(9E4)	4473.72	23.53	52.5
Pancreatic cancer(9D8)	3443.44	20.25	0
Pancreatic cancer(9D4)	3819.27	17.3	0
Pancreatic cancer(9BE)	3287.48	24.17	7.5
Pancreatic NAT(ADB)	2358	28.92	1.5
Pancreatic NAT(ADC)	2863.88	36.96	20.5
Pancreatic NAT(ADD)	3118.81	30.22	0
Pancreatic NAT(AED)	3211.96	26.31	46
Colon cancer(8A3)	1984.83	48.06	0
Colon NAT(8B6)	1682.5	39.46	0
Colon NAT(9F1)	2378.93	48.8	0
Colon cancer(9F2)	1931.28	46.1	0
Colon NAT(A1D)	2029.41	46.05	0
Colon cancer(9DB)	2278.96	44.08	0
Colon NAT(A15)	1674.01	45.41	1
Colon cancer(A14)	1360.97	35.04	2
Colon NAT(ACB)	1707.6	45.03	0
Colon cancer(AC0)	1894.33	46.06	0
Colon cancer(8A4)	1785.56	43.34	1
Colon NAT(ACD)	1797.75	44.1	7
Colon cancer(AC4)	2198.75	49.26	1
Colon NAT(AC2)	1847.84	43.83	0
Colon cancer(AC1)	1806.35	39.49	2
Colon NAT(ACC)	2013.34	39.08	2
Colon cancer(AC3)	1539.46	47.71	5
Breast cancer(9B7)	1857.03	46.65	22.5
Breast NAT(9CF)	1462.79	47.35	0
Breast cancer(9B6)	2133.12	47.71	11
Breast cancer(9C7)	2302.99	47.48	11.5
Colon cancer(8A6)	2093.72	45.39	4.5
Breast NAT(A11)	1508.35	45.43	2.5
Breast cancer(A1A)	2246.51	46.55	0
Breast cancer(9F3)	1881.09	46.54	10
Breast cancer(9B8)	2174.46	48.66	0
Breast NAT(9C4)	1670.58	48.93	6
Breast cancer(9EF)	1168.07	23.61	3
Breast cancer(9F0)	1506.95	28.54	1
Breast cancer(9B4)	1016.05	32.36	12
Breast cancer(9EC)	2526.83	47.27	9
Colon cancer(8A7)	1594.35	48.21	0
Colon cancer(8B7)	2091.33	40.64	3
Colon cancer(8A9)	2533.34	40.66	8
Colon cancer(8AB)	1638.43	30.62	2
Colon cancer(8AC)	1975.26	41.39	0
Colon NAT(8AD)	1851.09	49.21	0
Colon cancer(8B5)	1920.15	47.11	9
Cervical cancer(B08)	1393.31	2.02	0
Brain cancer(9F8)	1400.44	8.86	16
Brain cancer(9C0)	655.35	4.73	1
Brain cancer(9F7)	1403.07	0.42	0
Brain cancer(A00)	1509.09	3.25	0
Brain NAT(A01)	1159.94	0.43	0
Brain cancer(9DA)	1019.67	0.72	0
Brain cancer(9FE)	1352.85	2.77	0
Brain cancer(9C6)	1237.61	3.47	0
Brain cancer(9F6)	917.48	2.17	0
Cervical NAT(AEB)	826.9	1.64	0
Bladder NAT(23954)	521.75	0.44	0
Urinary cancer(AF6)	1007.77	1.4	0
Urinary cancer(B0C)	1256.43	1.31	0
Urinary cancer(AE4)	1219.17	1.23	0
Urinary NAT(B20)	1222.48	1.23	0
Urinary cancer(AE6)	1114.91	1.03	0
Urinary NAT(B04)	655.35	0.07	0
Urinary cancer(B07)	543.73	1.64	0
Urinary NAT(AF8)	1247.4	0.53	0
Cervical cancer(AFF)	1411.18	4.31	0
Ovarian cancer(9D7)	1221.47	0.63	0
Urinary cancer(AF7)	1138.73	1.3	0
Ovarian cancer(9F5)	1298.98	0	0
Ovarian cancer(A05)	1134.77	2.16	8
Ovarian cancer(9BC)	505	0.15	0
Ovarian cancer(9C2)	1025.23	0.93	0
Ovarian cancer(9D9)	1203.34	1.53	1.5
Ovarian NAT(AC7)	685.35	0.54	0
Ovarian NAT(AC9)	716.79	0.85	0
Ovarian NAT(ACA)	628.62	2.38	0
Cervical NAT(B1E)	1293.21	7.01	0
Ovarian NAT(AC5)	542.12	0.99	0
Cervical cancer(B00)	1512.53	9.92	0
Cervical NAT(AFA)	1136.08	8.76	0
Cervical cancer(B1F)	1782.82	18.96	0
Cervical NAT(B1C)	655.35	2.36	0
Brain cancer(9F9)	1508.5	5.08	13
Breast cancer(D34)	2470.88	0	0
Breast cancer(D35)	2602.08	0	0
Breast cancer(D36)	2909.53	0	2.5
Breast cancer(D37)	2811.77	0.05	0
Breast cancer(D38)	2986.78	0.38	7
Breast cancer(D39)	3026.22	0.04	0
Breast cancer(D3A)	3072.62	0.08	15
Breast cancer(D3B)	2571.28	0.02	0
Breast cancer(D3C)	3213.98	0.6	26.5
Breast cancer(D3D)	3484.57	2.5	34
Breast cancer(D3E)	2958.51	0.17	46
Breast cancer(D3F)	2937.01	1.88	23
Breast cancer(D40)	2751.61	1.2	37
Breast cancer(D42)	2171.59	0.8	0
Breast cancer(D43)	2962.09	4.5	0
Breast cancer(D44)	2558.08	2.95	43
Breast cancer(D45)	2667.3	3.59	26
Breast cancer(D46)	3190.77	2.25	43.5
SK-MES	2804.32	0.56	0
HLaC-79	3402.37	0	0
H226	2562.59	0	0
HCT-116	4221.68	0.09	5
IGROV-1	3243.07	0	0
MX-1	3253.75	0	0
C33A	3249.59	0	0
Daudi	2333.08	0.01	0
MV522	2727.71	0.94	2
RWP-2	2906.49	0	0
BON	2502.53	0.01	0
MiaPaCa	3604.78	0	23.5
H82	2357.18	2.19	10
H69	2759.55	0.12	0
Caki-2	2687.93	0	0
LNCaP	3352.46	0.41	5
A549	2593.12	0	0
DU145	3970.51	0.07	0
OVCAR-3	3230.65	0.14	0
HT-29	3381.64	0.07	28.5
DLD-2	3610.05	0.24	0
MCF-7	3326.73	1.78	2
H460	2464.22	0	0
SW620	2732.11	0	0
SK-OV-3	3519.75	0	4
MDA-231	3464.04	0.04	4
Caki-1	3801.64	0	0
PC-3	2214.23	0	0
LoVo	3237.95	0	0
Kidney NAT(10B1)	3041.27	6.44	30
Kidney cancer(10B2)	3798.53	1.31	34.5
Kidney NAT(10B3)	3315.43	0	25.5
Kidney cancer(10B4)	3519.14	0.16	0
Kidney NAT(10B5)	3017.75	0	14
Kidney cancer(10B6)	3702.61	0	8
Kidney NAT(10B7)	3060.89	0	2
Kidney cancer(10BA)	3437.01	0	0
Kidney NAT(10BB)	3157.99	0	2
Kidney cancer(10C0)	3590.87	0.77	5
Kidney NAT(10C1)	3012.3	0	6.5
Kidney cancer(10C4)	3186.48	0.02	0
Kidney NAT(10C5)	3618.74	0	14
Kidney cancer(10A8)	3514.51	0	10
Kidney NAT(10A9)	2771.76	1.14	16
Kidney cancer(10AA)	3793.55	0.4	110
Kidney NAT(10AB)	2978.06	0	21
Kidney cancer(10AC)	3656.35	0.05	44.5
Kidney NAT(10AD)	3299.97	2.13	57
Kidney cancer(10AE)	3456.21	0.57	23.5
Kidney NAT(10AF)	2593.7	0	0
Kidney cancer(10B0)	3529.2	0.67	58
Lymphoma(9BF)	2333.81	0	0
Lymphoma(9D2)	1327.77	0	0
Lymphoma(A04)	1450.41	0	0
Lymphoma(9DD)	1095.68	0	0
Lymphoma(F68)	865.62	0	0
Lymphoma(F6A)	862.12	0	0
Lymphoma(F6B)	624.66	0	0
Lymphoma(F6C)	1621.52	0	0
Lymphoma(F6D)	864.76	0	0
Lymphoma(F6E)	1030.71	0	0
Lymphoma(F6F)	1120.14	0	0
Lymphoma(F70)	891.53	0	0
Lymphoma(F71)	915.92	0	0
Lymphoma(F72)	1199.28	3.13	0
Lymphoma(F73)	1357.46	0	0
Lymphoma(F74)	993.02	0	0
Lymphoma NAT(1002)	2069.54	0	0
Lymphoma NAT(1004)	1928.51	0	0
Lymphoma NAT(1005)	1412.32	0	0
Lymphoma NAT(1007)	1668.28	0	0
Lymphoma NAT(1003)	1919.49	0	0
Lymphoma(9E3)	1791.94	0	14
Lymphoma(9D0)	1530.59	0	0
Lymphoma(9E1)	1677.97	0	0
Lymphoma(A0D)	2656.34	1.4	86
Lymphoma(9B5)	2336.21	0	0
Lymphoma(9D3)	1902.13	0	0
Normal Lung 4	4083.27	28.46	19.13
Normal Lung 5	4235.38	25.22	8.83
Normal Lung 1	2759.91	24.22	NA
Normal Lung 2	3656.2	20.99	20.46
Normal Lung 3	3157.31	22.69	28.57
SW1353 resting 1 h	3946.45	0.6	0
SW1353 resting 6 h	3263.46	0.12	0
SW1353 resting 16 h	2311.8	0	0
SW1353 IL-1b(1 ng/) 1 h	2686.83	0.16	0
SW1353 IL-1b(1 ng/) 6 h	3159.94	2	0
SW1353 IL-1b(1 ng/) 16 h	3557.88	0.62	0
SW1353 FGF20 (1 ug/)	3512.56	0.69	0
1 h
SW1353 FGF20 (1 ug/)	2510.14	0.06	0
16 h
SW1353 FGF20 (5 ug/)	3448.11	1.01	0
1 h
SW1353 FGF20 (5 ug/)	3598.07	0.64	0
6 h
SW1353 FGF20 (5 ug/)	3687.34	4.42	0
16 h
SW1353 FGF20 (1 ug/)	3569.19	0.17	0
IL-1b (1 ng/) 6 h
SW1353 FGF20 (1 ug/)	3970.28	0.01	0
IL-1b (1 ng/) 16 h
SW1353 FGF20 (5 ug/)	3011.45	0	0
IL-1b (1 ng/) 1 h
SW1353 FGF20 (5 ug/)	3184.88	2.69	0
IL-1b (1 ng/) 6 h
THP-1 aCD40 (1 ug/) 1 h	3545.99	0.07	0
THP-1 aCD40 (1 ug/) 6 h	2882.56	0.44	0
THP-1 LPS (100 ng/) 1 h	3131.64	0.74	0
THP-1 LPS (100 ng/) 6 h	2356.5	0.05	0
CCD1070SK TNFa (5	2888.01	0.78	0
ng/) 6 h
CCD1070SK TNFa (5	3029	0.39	0
ng/) 24 h
CCD1070SK IL-1b (1 ng/)	3307.91	5.76	0
24 h
THP-1 resting	3080.68	0.87	0
THP-1 aCD40 (1 ug/) 24 h	2032.49	0.82	0
THP-1 LPS (100 ng/) 24 h	1597.29	3.58	0
CCD1070SK IL-1b (1 ng/)	3026.56	3.51	0
6 h
LC 18 hr	2725.87	0.36	0
LC-IL-! 18 hr	1474.79	2.66	0
Astrocyte_IL1B_1 hr_a	3116.77	10.04	0
Astrocyte_IL1B_6 hr_a	3119.7	16.51	0
Astrocyte_IL1B_24 hr_a	3142.98	13.81	0.7
SHSY 5Y Undifferentiated	3166.23	14.61	4.17
SHSY 5Y Differentiated	2959.01	8.5	2.23
LC 0 hr	1880.7	0	0
Normal Fetal Kidney	2011.8	0	0
Normal Liver	2053.67	3.81	0
Normal Fetal Liver	3555.17	0	0
Normal Fetal Lung	4164.55	0	24.3
Normal Salivary Gland	3466.36	0	0
Normal Fetal Skeletal	2504.59	0	0
Muscle
Normal Thyroid	3566.17	0	20.36
Normal Trachea	3596.15	0	31.2
LC-IL-1 0 hr	2560.23	0	0
Heart pool	3167.78	0	0
Pituitary Pool	2908.48	0	0
Spleen Pool	2068.62	0	0
Stomach Pool	2826.7	0	0
Testis Pool	3348.7	0	446.08
Thymus Pool	2653.82	0	0
Small Intestine- 5 donor	3795.64	0	40.57
pool
Lymph node- 5 donor	4339.52	0	27.88
pool
Kidney- 5 donor pool	3347.34	0	0
Jurkat Resting	3779.74	0.48	.8.44
Jurkat CD3 (500 ng/ml)	2459.46	1.68	5.37
6 hr A
Jurkat CD3 (500 ng/ml)	1897.6	0.08	0
24 hr A
Jurkat CD3	1867.35	0.68	0
(500 ng/ml) + CD28 (1 ug/ml)
6 hr A
Jurkat CD3	1574.07	0.35	0
(500 ng/ml) + CD28(1 ug/ml)
24 hr A
control (no treatment)_1	5400.28	2.01	3.06
hr
10 ng/ml IL-1b_1 hr	5250.91	1.51	1.26
10 ng/ml TNF-a_1 hr	5668.06	2.55	0
200 uM BzATP_1 hr	5619.87	0.31	0
control (no treatment)_5	5630.13	1.02	3.91
hr
10 ng/ml IL-1b_5 hr	6332.12	10.52	6.6
10 ng/ml TNF-a_5 hr	6070.17	6.37	6.7
200 uM BzATP_5 hr	6425.22	2.39	0.68
control (no treatment)_24	4825.87	3.5	1.82
hr
10 ng/ml IL-1b_24 hr	5349.28	9.73	7.4
10 ng/ml TNF-a_24 hr	5672.31	4.97	0
200 uM BzATP_24 hr	4814.1	0.51	0
Alzheimer's disease	1854.86	14.76	66.42
B4951
Alzheimer's disease	2540.02	19.95	33.78
B4953
Alzheimer's disease	1757.68	22.42	48.81
B5018
Alzheimer's disease	1491.9	18.37	47.93
B5019
Alzheimer's disease	2247.49	18.04	29.37
B5086
Alzheimer's disease	2150.92	19.76	47.05
B5096
Alzheimer's disease	732.56	15.93	12.01
B5098
Alzheimer's disease	1841.99	18.04	23.89
B5129
Alzheimer's disease	3233.87	21.56	22.45
B5210
Control B4810	2987.22	21.85	20.62
Control B4825	2903.91	18.74	35.61
Control B4930	2287.12	22.69	18.28
Control B4932	3424.98	20.12	43.68
Control B5024	3859.32	22.42	43.32
Control B5113	1897	17.87	26.67
Control B5140	1901.93	18.88	45.11
Control B5190	1284.69	15.26	22.26
Control B5220	2225.75	18.7	23.72
Control B5245	2119.39	21.5	15.57
AH3 B3791	2202.74	19.73	25.47
AH3 B3855	1849.89	17.93	15.46
AH3 B3877	2144.15	17.01	12.31
AH3 B3893	2103.76	16.34	24.05
AH3 B3894	1820.82	17.31	14.5
AH3 B3949	1607.86	23.9	16.42
AH3 B4477	1602.58	20.32	26.08
AH3 B4540	2260.92	22.79	23.84
AH3 B4577	2142.42	22.59	19
AH3 B4639	1550.43	21.89	18.45
Schizophrenia	2468.43	21.23	16.04
hippocampus 683
Depression hippocampus	1473.83	18	0
487
Depression hippocampus	2481.12	10.69	45.22
600
Normal hippocampus	2624.25	33.19	5.87
2407a
Normal hippocampus	2114.72	21.4	32.77
1042
Depression hippocampus	1448.13	10.6	5.32
2767
Depression hippocampus	1836.77	47.98	28.75
567
Control hippocampus	2752.14	14.38	32.77
3175
Depression hippocampus	1735.6	9.4	27.89
3096
Depression hippocampus	2784.26	17.28	19.75
1491
Depression hippocampus	2241.25	16.73	20.61
2540
Schizophrenia	1923.26	16.97	36.6
hippocampus 2798
Control hippocampus	2605.59	14.97	10.13
1973
Normal hippocampus and	2031.45	13.85	5.41
amygdala 2601
Schizophrenia	1621.43	21.03	28.49
hippocampus 2785
Schizophrenia	3271.31	39.54	10.42
hippocampus 484
Normal hippocampus	2806.68	21.69	2.74
2556
Depression hippocampus	2705.56	15.83	31.71
1158
Control hippocampus 552	3378.83	21.65	35.16
Schizophrenia	2304.06	12.06	43.45
hippocampus 1737
Normal hippocampus	3335.3	17.54	12.53
1239
Normal hippocampus	3068.38	14.64	13.98
1465
Normal hippocampus	1323.77	4.6	1.66
3080
Normal hippocampus 738	4229.67	12.96	17.68
Schizophrenia	2067.82	12.78	10.64
hippocampus 2586
Normal hippocampus	3306.02	13.41	16.64
2551
Depression hippocampus	2352.1	13.53	17.77
588
Depression hippocampus	3291.7	13.05	18.71
529
Depression hippocampus	1686.08	11.37	0
and dentate gyrus
Schizophrenia amygdala	2136.57	0.55	0
2586
Normal substantia nigra	1240.83	0.03	0
234
Normal substantia nigra	1515.69	14.19	0
1065
Normal substantia nigra	1341.77	0	0
3236
Normal substantia nigra	3718.91	0.43	20.11
2551
Normal substantia nigra	1003.1	0	0
1597
Control thalamus 552	948.15	0.02	9.28
Control thalamus 566	1698.42	0	1.94
Control thalamus 606	2625.59	0.31	0
Control thalamus 738	2464.52	0	17.85
Control thalamus 1065	2991.38	0	49.27
Control thalamus 1092	2416.75	0	0
Control thalamus 1597	2389.84	0	0
Control thalamus 2253	1602.4	0	0
Control thalamus 2551	3017.98	0	4.74
Depression thalamus 588	2245.45	0.29	0
Depression thalamus 600	1442.56	0	0
Depression thalamus 721	1921.28	0	0
Depression thalamus 728	3113.17	4.33	5.65
Depression thalamus 759	2433.85	0	0
Depression thalamus 881	2456.7	0	0
Schizophrenia thalamus	1952.08	0	0
477
Schizophrenia thalamus	3553.95	0	2.48
532
Schizophrenia thalamus	3798.02	0	4.05
683
Schizophrenia thalamus	3260.82	0.03	35.76
544
Schizophrenia thalamus	2246.95	0	0
1671
Schizophrenia thalamus	1958.75	0.01	0
1737
Schizophrenia thalamus	1953.64	0	0
2464
Schizophrenia thalamus	3338.49	0	1.32
2586
Depression amygdala	1936.43	0	0
600
Depression amygdala	2378.2	0	0
759
Depression anterior	2808.48	0	0
cingulate 759
Control amygdala 552	3675.87	0.36	8.38
Control anterior cingulate	3115.46	0.67	26.13
482
Depression anterior	1964.87	0	0
cingulate 721
Control amygdala 3175	2674.16	0.04	17.28
Depression anterior	2389.83	0.06	17.03
cingulate 600
Depression anterior	2629.92	0	5.02
cingulate 588
Control anterior cingulate	3605.03	0.79	25.02
3175
Control anterior cingulate	2414.64	0	0
606
Depression anterior	2397.28	1.2	11.01
cingulate 567
Depression amygdala	3410.76	3.1	9.03
588
Control anterior cingulate	2445.09	3.01	39.59
3080
Control anterior cingulate	2520	5.45	29.25
2601
Control anterior cingulate	3118.04	0.76	28.22
1042
Control anterior cingulate	2913.66	1.45	37
3236
Control amygdala 1502	4253.4	9.62	38.28
Control anterior cingulate	2624.08	8.86	25.99
807
Control amygdala 1597	3710.89	11.88	14.82
Parkinson's substantia	2457.51	0.25	19.69
nigra 2842
Parkinson's substantia	1548.58	0	0
nigra 2917
Schizophrenia amygdala	2009.89	0	0
544
Schizophrenia amygdala	730.94	0	0
532
Depression amygdala	2408.1	0	4.11
2540
Parkinson's substantia	1544.99	0	0
nigra 2899
Depression anterior	3015.65	0	NA
cingulate 881

Example E

Expression of NOV 7, CG55690-05 Using Baculovirus Expression System

[0765] A 0.425 kb BamHI-XhoI fragment containing the CG55690-05 sequence was subcloned into the pMelV5His (CuraGen Corporation) insect expression vector to generate plasmid 1638. Following the standard procedures (Invitrogen pBlueBac protocol), high titer virus stocks were prepared and Sf9 cells were infected. The culture media was harvested after 5 days post-infection and assayed for CG55690-05 protein expression by Western blot (reducing conditions) using an anti-V5 antibody. CG55690-05 is expressed as 27 kDa protein.

Example F

Expression of NOV 11, CG94562-02 in Human Embryonic Kidney 293 Cells

[0766] A 0.644 kb BamHI-XhoI fragment containing the CG94562-02 sequence was subcloned into BamHI-XhoI digested pCEP4/Sec to generate plasmid 1328. The resulting plasmid 1328 was transfected into 293 cells using the LipofectaminePlus reagent following the manufacturer's instructions (Gibco/BRL). The cell pellet and supernatant were harvested 72 h post transfection and examined for CG94562-02 expression by Western blot (reducing conditions) using an anti-V5 antibody. CG94562-02 is expressed as a 31 kDa protein secreted by 293 cells.

OTHER EMBODIMENTS

[0767] Although particular embodiments are disclosed herein in detail, this is 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 will 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 82.

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 82.

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 82.

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 82.

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 82 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 82.

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 82.

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 82.

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 82.

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 82, 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 82.

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 82.

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.